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EDITORS

BYRON J. BAILEY, M.D.


Wiess Professor and Chairman
Department of Otolaryngology
University of Texas Medical Branch at Galveston
Galveston, Texas
GERALD B. HEALY, M.D.
Otolaryngologist-in-Chief
Department of Otolaryngology
Childrens Hospital
Professor of Otology and Laryngology
Harvard Medical School
Boston, Massachusetts
JONAS T. JOHNSON, M.D.
Vice Chairman
Department of Otolaryngology
University of Pittsburgh Medical Center Health Systems
The Eye and Ear Institute of Pittsburgh
Professor
Department of Otolaryngology and Radiation Oncology
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania
ROBERT K. JACKLER, M.D.
Professor of Otolaryngology and Neurological Surgery
Department of OtolaryngologyHead and Neck Surgery
University of CaliforniaSan Francisco Medical Center
San Francisco, California
KAREN H. CALHOUN, M.D., F.A.C.S.
Professor and Vice Chair
Department of Otolaryngology
University of Texas Medical Branch at Galveston
Galveston, Texas
HAROLD C. PILLSBURY III, M.D.
Attending Physician
University of North Carolina Hospitals
Professor and Chief
Division of OtolaryngologyHead and Neck Surgery
University of North Carolina at Chapel Hill
School of Medicine
Chapel Hill, North Carolina
M. EUGENE TARDY, JR., M.D.
Professor of Clinical OtolaryngologyHead and Neck Surgery
Director, Division of Facial Plastic and Reconstructive Surgery
University of Illinois School of Medicine at Chicago
Northwestern University Medical School
Chicago, Illinois
Professor of Clinical OtolaryngologyHead and Neck Surgery
Department of Otolaryngology
Indiana University School of Medicine
Bloomington, Indiana
295 contributors
Illustrated by Anthony Pazos and Christine Gralapp


CONTRIBUTING AUTHORS
Peter A. Adamson, M.D., F.R.C.S.C., F.A.C.S. Surgeon, Department of Otolaryngology,
Toronto General Hospital, University Health Network; and, Professor, Department of
Otolaryngology, University of Toronto, Toronto, Ontario, Canada
Eugenio A. Aguilar III, M.D. ERMOSA Centre for Plastic, Reconstructive and Cosmetic
Surgery, Houston, Texas
James Alex, M.D. Associate Professor, Department of OtolaryngologyHead and Neck
Surgery, University of Illinois Medical Center and St. Joseph Hospital, Chicago, Illinois
Mark A. Alford, M.D. Chief, Department of Oculoplastic Surgery, Ophthalmology
Associates, Fort Worth, Texas
Ramsey Alsarraf, M.D., M.P.H. Director, Newbury Center for Cosmetic Facial Plastic
Surgery, Associate Staff, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
Ronald G. Amedee, M.D. Professor and Chairman, Department of Otolaryngology,
Tulane University School of Medicine, New Orleans, Louisiana
Milan R. Amin, M.D. Director, Center for Voice & Swallowing, Hahnemann University
Hospital; and, Assistant Professor, Department of OtolaryngologyHead and Neck
Surgery, Hahnemann School of Medicine, Philadelphia, Pennsylvania
Peter E. Andersen, M.D. Department of OtolaryngologyHead and Neck Surgery,
Oregon Health Sciences University, Portland, Oregon
J. Todd Andrews, M.D. Houston Center for Facial Plastic Surgery, Houston, Texas
Patrick J. Antonelli, M.D. Department of Otolaryngology, Shands Hospital; and,
Associate Professor, Department of Otolaryngology, University of Florida School of
Medicine, Gainesville, Florida
Steven B. Aragon, M.D., D.D.S. Department of Otolaryngology, Littleton Hospital,
Littleton, Colorado; and, Assistant Clinical Professor, Department of Otolaryngology,
University of Colorado School of Medicine, Denver, Colorado
H.A. Arts Department of Otorhinolaryngology, University of Michigan, Ann Arbor,
Michigan
Benjamin F. Asher, M.D. Instructor in Surgery, Dartmouth Medical School, Berlin,
Vermont
Byron J. Bailey, M.D. Wiess Professor and Chairman, Department of Otolaryngology,
University of Texas Medical Branch at Galveston, Galveston, Texas
R. Stanley Baker, M.D. Chairman, Department of Otolaryngology, Integris-Baptist
Medical Center, Oklahoma City, Oklahoma
Carey D. Balaban, Ph.D Professor, Department of Otolaryngology, Eye and Ear Institute
of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Stephen F. Bansberg, M.D. Department of Otolaryngology, Mayo Clinic, Scottsdale,
Arizona
David M. Barrs, M.D. Associate Clinical Professor, Department of Otolaryngology,
Duke University, Durham, North Carolina
Linda M. Bartoshuk, M.D. Professor, Department of Surgery, Section of
Otolaryngology, Yale University School of Medicine, New Haven, Connnecticut
Carol A. Bauer, M.D. Assistant Professor, Division of Otolaryngology, Southern Illinois
University School of Medicine, Springfield, Illinois
Terry S. Becker, M.D. Los Angeles CountyUniversity of Southern California Medical
Center, Los Angeles, California
Michael S. Benninger, M.D. Department of OtolaryngologyHead and Neck Surgery,
Henry Ford Hospital, Detroit, Michigan
Gerald S. Berke, M.D. Division of OtolaryngologyHead and Neck Surgery, University
of CaliforniaLos Angeles, Los Angeles, California
Mark L. Bernstein, D.D.S. Professor, Department of Surgical and Hospital Dentistry,
University of Louisville School of Dentistry, Louisville, Kentucky
Fred H. Bess, M.D. Dan Maddox Hearing Aid Research Laboratory, Vanderbilt Bill
Wilkerson Center, Nashville, Tennessee
Charles D. Bluestone, M.D. Director, Department of Pediatric Otolaryngology, Professor
of Pediatric Otolaryngology, Childrens Hospital of Pittsburgh Eberly Pittsburgh,
Pennsylvania
Derald E. Brackmann, M.D., F.A.C.S. Clinical Professor of Otolaryngology/Head and
Neck Surgery, Clinical Professor of Neurosurgery, University of Southern California
School of Medicine; and, Director, House Ear Clinic, St. Vincent Medical Center, Los
Angeles, California
John M. Brockenbrough, M.D. Department of Otolaryngology, Loyola University
School of Medicine, Maywood, Illinois
Bruce E. Brockstein, M.D. Attending in Medicine, Evanston Northwestern Healthcare;
and, Assistant Professor of Medicine, Northwestern University, Evanston, Illinois
Hilary A. Brodie, M.D., Ph.D. Associate Professor and Chair, Department of
Otolaryngology, University of CaliforniaDavis Medical Center; and, Otolaryngology
Research Laboratories, University of CaliforniaDavis, Davis, California
Linda Brodsky, M.D. Chief, Pediatric Otolaryngology, Childrens Hospital of
Buffalo/Kaleida Health; and, Professor, Departments of Otolaryngology and Pediatrics,
State University of New YorkBuffalo, School of Medicine and Biomedical Sciences,
Buffalo, New York
Patrick E. Brookhouser, M.D. Director, Boys Town National Research Hospital; and,
Professor and Chairman, Department of Otolaryngology and Human Communication,
Creighton University School of Medicine, Omaha, Nebraska
D.W. Buchbinder, M.D. Professor of Oral and Maxillofacial Surgery, Department of
Otolaryngology, Mount Sinai Medical Center, New York, New York
Jeffrey D. Bunn, M.D. Resident in Otolaryngology, Division of OtolaryngologyHead
and Neck Surgery, Loma Linda University Medical Center, Loma Linda, California
Gary C. Burget, M.D., F.A.C.S. Clinical Associate Professor, Section of Reconstructive
Surgery, University of Chicago, Chicago, Illinois
Matthew D. Byers, M.D. Fellow, Facial Plastic and Reconstructive Surgery, Premier
Image Cosmetic and Laser Center, Atlanta, Georgia; and, Associate, Florida Ear, Sinus &
Facial Plastics, Sarasota Memorial Hospital, Sarasota, Florida
Karen H. Calhoun, M.D., F.A.C.S. Professor and Vice Chair, Department of
Otolaryngology, University of Texas Medical Branch at Galveston, Galveston, Texas
Deborah L. Carlson, Ph.D. Director, Center for Audiology and Speech Pathology,
University of Texas Medical Branch at Galveston, Galveston, Texas
Ricardo L. Carrau, M.D. The Eye & Ear Institute, Pittsburgh, Pennsylvania
Mark S. Chambers, DM.D., M.S., FAAMP Assistant Professor, Department of Head and
Neck Surgery, Section of Oncologic Dentistry and Prosthodontics, University of Texas
M.D. Anderson Cancer Center, Houston, Texas
C.Y. Joseph Chang, M.D. Assistant Professor, Department of OtolaryngologyHead
and Neck Surgery, University of TexasHouston, Houston, Texas
Douglas Chepeha, M.D. Assistant Professor, Department of OtolaryngologyHead and
Neck Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan
Richard A. Chole, M.D., Ph.D. Lindberg Professor and Head, Department of
Otolaryngology, Washington University School of Medicine, Barnes-Jewish Hospital, St.
Louis, Missouri
Gary L. Clayman, M.D., D.D.S. Deputy Chairman, Department of Head and Neck
Surgery, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Amy R. Coffey, M.D. Assistant Professor, Department of Otolaryngology, Universtiy of
Texas Southwestern Medical Center, Dallas, Texas
Newton J. Coker, M.D. Attending Physician, Department of Otorhinolaryngology,
Methodist Hospital; and, Professor, Bobby R. Alford Department of Otorhinolaryngology
and Communicative Sciences, Baylor College of Medicine, Houston, Texas
John R. Coleman, Jr., M.D. Atlanta Center for ENT and Facial Plastic Surgery, Atlanta,
Georgia
Adriane P. Concus, M.D. Department of OtolaryngologyHead and Neck Surgery,
Henry Ford Hospital, Detroit, Michigan; and, Clinical Assistant Professor, Department of
OtolaryngologyHead and Neck Surgery, University of Michigan, Ann Arbor, Michigan
John U. Coniglio, M.D. Assistant Professor, Division of OtolaryngologyHead and
Neck Surgery, Strong Memorial Hospital, University of Rochester, Rochester, New York
Peter D. Costantino, M.D. Co-Director, Center for Cranial Base Surgery, Department of
Otolaryngology, University Hospital, Columbia University College of Physicians and
Surgeons, New York, New York
Robin T. Cotton, M.D. Director, Department of Pediatric Otolaryngology, Childrens
Hospital Medical Center, Cincinnati, Ohio
Leonard V. Covello, M.D. Facial Plastic Surgery Association, Houston, Texas
Dennis M. Crockett, M.D. Associate Professor, Division of OtolaryngologyHead and
Neck Surgery, University of Southern California, School of Medicine, Los Angeles,
California
Michael J. Cunningham, M.D. Surgeon, Department of Otolaryngology, Massachusetts
Eye and Ear Infirmary; and, Associate Professor, Department of Otology and
Laryngology, Harvard Medical School, Boston, Massachustetts
Samuel J. Cunningham, M.D., Ph.D. Research Fellow, Department of Otolaryngology,
University of Texas Medical Branch at Galeveston, Galveston, Texas
Steven H. Dayan, M.D. Clinical Assistant Professor; Department of Otolaryngology
Head and Neck Surgery, University of Illinois Medical Center, Chicago, Illinois
Albert R. De Chicchis, Ph.D. Assistant Professor, Communication Sciences and
Disorders, University of Georgia, Athens, Georgia
Douglas D. Dedo, M.D. Physician, Department of Enterology, Good Samaritan/ St.
Marys Hospital, West Palm Beach, Florida; and, Clinical Assistant Professor,
Department of OtolaryngologyHead and Neck Surgery, University of Miami Medical
School, Miami, Florida
Daniel A. Deems, M.D., Ph.D., F.A.C.S. Department of Surgery; University Ear, Nose and
Throat Associates, and Sarasota Memorial Hospital, Sarasota, Florida
Craig S. Derkay, M.D. Medical Director and Chief of Service, Department of
Otolaryngology, Childrens Hospital of the Kings Daughters; and, Professor of
Otolaryngology and Pediatrics, Vice-Chairman, Department of Otolaryngology, Eastern
Virginia Medical School, Norfolk, Virginia
Ronald W. Deskin, M.D. Director of Fellowship Program, Texas Childrens Hospital;
and, Associate Professor, Department of Otolaryngology, Baylor College of Medicine,
Houston, Texas
Lawrence W. DeSanto, M.D. Mayo Clinic Scottsdale, Scottsdale, Arizona
Eric J. Dierks, M.D., D.M.D. Vice Chairman, Department of Oral and Maxillofacial
Surgery, Oregon Health Sciences University, Director of Head & Neck Fellowship,
Legacy Emanuel Hospital, Portland, Oregon
Robert A. Dobie, M.D. Director, Extramural Research, National Institute on Deafness
and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland;
and, Visiting Professor, Department of Otolaryngology, Johns Hopkins University,
Baltimore, Maryland
Brennan T. Dodson, M.S.I.V. University of Oklahoma, College of MedicineTulsa,
Tulsa, Oklahoma
William C. Donlon, M.D. Active Staff, Department of Surgery, Mills-Peninsula
Hospitals, Burlingame and San Mateo, California; and, Department of Surgery, Sequoia
Hospital, Redwood City, California
Richard L. Doty, Ph.D. Director, Smell and Taste Center, and Department of
Otorhinolaryngology, University of Pennsylvania Medical Center, Philadelphia,
Pennsylvania
Amelia F. Drake, M.D. Division of Otolaryngology, University of North Carolina,
Chapel Hill, North Carolina
Brian P. Driscoll, M.D. Clinical Instructor, Department of Otolaryngology, University of
Texas Medical Branch at Galveston, Galveston, Texas
Colin L.W. Driscoll, M.D. Senior Associate Consultant, Department of
Otorhinolaryngology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
James A. Duncavage, M.D. Department of Otolaryngology, Vanderbilt University
Medical Center, Nashville, Tennessee
Michael E. Dunham, M.D. Department of Pediatric Otolaryngology, Childrens
Memorial Hospital; and, Assistant Professor of Otolaryngology Northwestern University,
Chicago, Illinois
Robin A. Dyleski, M.D. Vice Chief, Department of Pediatric Otolaryngology, Arkansas
Childrens Hospital; and, Assistant Professor or Otolaryngology, Head and Neck
Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas
Deborah Eaton, M.D. Department of Otolaryngology, University of Texas Southwestern
Medical Center, Dallas, Texas
David E. Eibling, M.D., F.A.C.S. Chief, Department of OtolaryngologyHead and Neck
Surgery, Veterans Administration Pittsburgh; and, Professor, Department of
Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania
David W. Eisele, M.D. Professor, Department of OtolaryngologyHead and Neck
Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
Lee D. Eisenberg, M.D. ENT and Allergy Associates, Englewood, New Jersey
Jason J. Emer, M.D. Research Division, Department of OtolaryngologyHead and
Neck Surgery, University of Illinois College of Medicine, Chicago, Illinois
Ramon M. Esclamado, M.D. Vice Chair and Head, Department of Otolaryngology
Head and Neck Surgery, Cleveland Clinic Foundation, Cleveland, Ohio; and, Associate
Professor, Department of Otolaryngology, Ohio State University, Columbus, Ohio
George W. Facer, M.D., F.A.C.S. Professor, Department of Otorhinolaryngology, Mayo
Clinic and Mayo Graduate School of Medicine, Rochester, Minnesota
David N. F. Fairbanks, M.D. Clinical Professor, Department of Otolaryngology, George
Washington University School of Medicine, Washington, D.C.
Michael O. Ferguson, M.D. Department of OtolaryngologyHead and Neck Surgery,
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Alan G. Finkel, M.D. Director, University Headache Clinic, University of North Carolina
Hospitals; and, Associate Professor, Department of Neurology, University of North
Carolina, Chapel Hill, North Carolina
Daniel M. Fliss, M.D. Director, Skull Base Unit, Department of OtolaryngologyHead
and Neck Surgery, Sourasky Medical Center, Tel Aviv, Israel; and, Professor of
OtolaryngologyHead and Neck Surgery, Faculty of Health Sciences, Ben-Gurion
University of the Negev, Beer Sheva, Israel
Karen J. Fong, M.S., M.D. Assistant Professor, Department of OtolaryngologyHead
and Neck Surgery, Oregon Health Sciences University, Portland, Oregon
Robert Frankenthaler, M.D. Assistant Surgery in Otology and Laryngology, Division of
Otolaryngology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Marvin P. Fried, M.D. Professor and University Chairman, Department of
Otolaryngology, Albert Einstein College of Medicine, Montefiore Medical Center,
Bronx, New York
Ellen M. Friedman, M.D. Pediatric Otolaryngology, Texas Childrens Hospital, Houston,
Texas
Michael Friedman, M.D. Professor and Chairman, Section of Head and Neck Surgery,
Rush Medical College, Rush-Presbyterian-St. Lukes Medical Center, Chicago, Illinois
Norman R. Friedman, M.D. Assistant Professor, Department of Otolaryngology,
Childrens Hospital, Denver, Colorado
Robert W. Gayler, M.D. Associate Professor of Radiology, Department of Radiology
and Radiological Sciences, The Johns Hopkins Medical Institution, Baltimore, Maryland
Mark E. Gerber, M.D., F.A.A.P. Department of Pediatric Otolaryngology, Childrens
Memorial Hospital; and, Assistant Professor, Department of OtolaryngologyHead and
Neck Surgery, Northwestern University Medical School, Chicago, Illinois
F. Brian Gibson, M.D. Assistant Clinical Professor, Department of Otolaryngology,
Vanderbilt University; and, Randolph ENT Associates, Charlotte, North Carolina
Jack Gluckman, M.D. University of Cincinatti Medical Center, Cincinatti, Ohio
Brian S. Goldstein, DO Clinical Fellow, Division of Neuroradiology, Department of
Diagnostic Radiology, Georgetown University Medical Center, Washington, D.C.
Harsha V. Gopal, M.D. Division of Otolaryngology, Beth Israel Deaconess Medical
Center; and, Assistant Professor, Otology and Laryngology, Harvard Medical School,
Boston, Massachusetts
J. Douglas Green, Jr., M.D. Jacksonville Hearing and Balance Institute, and Baptist
Medical Center, Jacksonville, Florida
Carla DeLassus Gress, Sc.D, C.C.C.-Slp Manager, University of CaliforniaSan
Francisco Voice Center, University of CaliforniaSan Francisco; and, Assistant Clinical
Professor, Department of Otolaryngology, University of CaliforniaSan Francisco, San
Francisco, California
A. Julianna Gulya, M.D. Chief of Clinical Trials, Epidemiology, and Biostatistics
Section, National Institutes of Health/ NIDCD, Bethesda, Maryland; and, Clinical
Professor of Otolaryngology, George Washington University, Washington, D.C.
Ray O. Gustafson, M.D. Assistant Professor of Otolaryngology, Department of
Otolaryngology, Mayo Clinic, Rochester, Minnesota
James W. Hall III, Ph.D. Clinical Professor of Audiology, Department of
Communicative Disorders, University of Florida Health Science Center, Gainesville,
Florida
Jeffrey P. Harris, M.D., Ph.D., F.A.C.S. Professor and Chief, Division of
OtolaryngologyHead and Neck Surgery, University of CaliforniaSan Diego School
of Medicine, San Diego, California
George T. Hashisaki, M.D. Assistant Professor, Department of OtolaryngologyHead
and Neck Surgery, University of Virginia, Charlottesville, Virginia
David S. Haynes, M.D. Department of Otology and Neurotology, Vanderbilt University
Medical Center, St. Thomas Hospital, Nashville, Tennessee
Gerald B. Healy, M.D. Otolaryngologist-in-Chief, Department of Otolaryngology,
Childrens Hospital; and, Professor of Otology and Laryngology, Harvard Medical
School, Boston, Massachusetts
David A. Hecht, M.D. Phoenix, Arizona
David Hendrick, M.D. Department of OtolaryngologyHead and Neck Surgery,
University of Illinois Medical Center and St. Joseph Hospital, Chicago, Illinois
Edward J. Hepworth, M.D. Resident, Division of Otolaryngology, Reconstructive and
Plastic Surgery, University of New Mexico Health Sciences Center, Albuquerque, New
Mexico
Marcelo Hochman, M.D. Department of Otolaryngology, Medical University of South
Carolina, Charleston, South Carolina
Lauren D. Holinger, M.D. Head, Division of Pediatric Otolaryngology and Department
of Communicative Disorders, Childrens Memorial Hospital; and, Professor, Department
of Otolaryngology, Head and Neck Surgery, Northwestern Medical School, Chicago,
Illinois
G. Richard Holt, M.D. Executive Vice President, American Academy of
OtolaryngologyHead and Neck Surgery, Alexandria, Virginia
Jean Edwards Holt, M.D. Department of Ophthalmology, The University of Texas
Health Science Center, San Antonio, Texas
R. Jeffrey Hood, M.D. Chief Resident, Department of OtolaryngologyHead and Neck
Surgery, University of Virginia Health System, Charlottesville, Virginia
David H. Hussey, M.D. Professor, Department of Radiation Oncology, University of
Texas Health Science Center, San Antonio, Texas
Ahmed S. Ismail, M.D. Faculty of Medicine, University of Alexandria; and, Assistant
Lecturer Depart of OtolaryngologyHead and Neck Surgery, Alexandria, Egypt
Robert K. Jackler, M.D. Department of OtolaryngologyHead and Neck Surgery,
University of CaliforniaSan Francisco Medical Center; and, Professor of
Otolaryngology and Neurological Surgery, University of CaliforniaSan Francisco, San
Francisco, California
Charlotte Jacobs, M.D. Department of Medicine, Stanford University Medical Center,
Palo Alto, California
Bruce W. Jafek, M.D., F.A.C.S., F.R.S.M. Staff, Department of Otolaryngology, University
of Colorado Hospital; and, Professor, Department of Otolaryngology, University of
Colorado Medical School, Denver, Colorado
Ivo P. Janecka, M.D. Longwood Skull Base Program, Harvard Medical School, Boston,
Massachusetts
Susan D. John, M.D. Chief, Pediatric Radiology Section, Memorial/Hermann Childrens
Hospital; and, Associate Professor, Department of Radiology, University of Texas
Houston Medical School, Houston, Texas
Michael E. Johns, M.D. Executive Vice President for Health Affairs, Director, The
Robert W. Woodruff Health Sciences Center; and, Chairman of the Board and Chief
Executive Officer, Emory Healthcare, Emory University, Atlanta, Georgia
Steve Johnson, M.D. University of Colorado Health Sciences Center, Denver, Colorado
Jonas T. Johnson, M.D. Vice Chairman, Department of Otolaryngology, University of
Pittsburgh School of Medicine; and, Professor, Department of Otolaryngology and
Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh,
Pennsylvania
Anne C. Jones, D.D.S. Associate Professor, Department of Pathology, University of
Texas Health Science Center, San Antonio, Texas
Kim R. Jones, M.D., Ph.D. Carolina ENT, Chapel Hill, North Carolina
Eric M. Joseph, M.D. Clinical Assistant Instructor, Department of Otolaryngology, Long
Island College Hospital, Brooklyn, New York
Frank M. Kamer, M.D. Clinical Professor, Division of Head and Neck Surgery,
Department of Surgery, University of CaliforniaLos Angeles, Los Angeles, California
Donald B. Kamerer, M.D. Professor, Department of Otolaryngology, University of
Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Haskins E. Kashima, M.D. Professor, Departments of Otolaryngology/Head and Neck
Surgery and Oncology, Johns Hopkins Medical Institution, Baltimore, Maryland
Edward E. Kassel, D.D.S., M.D. Department of Medical Imaging, Mount Sinai Hospital
and University Health Network, Toronto, Ontario, Canada
Robert M. Kellman, M.D. Professor and Chairman, Department of Otolaryngology, State
University of New York, Upstate Medical University, Syracuse, New York
Margaret A. Kenna, M.D. Associate in Otolaryngology, Childrens Hospital; and,
Associate Professor of Otology and Laryngology, Harvard Medical School, Boston,
Massachusettes
David W. Kennedy, M.D. Professor and Chair, Department of Otolaryngology,
University of Pennsylvania Medical Center; and, Professor, Department of
OtorhinolaryngologyHead and Neck Surgery, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania
Eugene B. Kern, M.D. Department of Otolaryngology, Mayo Clinic, Rochester,
Minnesota
Helen H. Kim, M.D. Department of Surgery and Otolaryngology, Albert Einstein College
of Medicine, Montefiore Medical Center, Bronx, New York
H. Jeffrey Kim, M.D. Assistant Professor, Department of OtolaryngologyHead and
Neck Surgery, Medstar-Georgetown, Washington, D.C.
Karen I. Kirk, M.D. Department of Otolaryngology, Indiana University School of
Medicine, Indianapolis, Indiana
Paul H. Kispert, M.D. Assistant Professor, Department of Surgery, Dartmouth Medical
School, Lebonon, New Hampshire
Sharen J. Knudsen, M.D. Beaver Medical Group, Inc., Highland, California
Peter J. Koltai, M.D., F.A.C.S., F.A.A.P. Head, Section of Pediatric Otolaryngology,
Cleveland Clinic Foundation, Cleveland, Ohio
Raymond J. Konior, M.D. Clinical Associate Professor, Department of Otolaryngology,
Loyola University Medical Center, Maywood, Illinois
Horst R. Konrad, M.D. Professor and Chairman, Division of Otolaryngology, Southern
Illinois University School of Medicine, Springfield, Illinois
Theda C. Kontis, M.D. Assistant Professor, Department of OtolaryngologyHead and
Neck Surgery, Johns Hopkins Medical Institutions, Facial Plastic Surgicenter, Owings
Mills, Maryland
Frank C. Koranda, M.D. President, Midwest Medical Specialists, Shawnee Mission,
Kansas; and, Associate Clinical Professor, OtolaryngologyHead and Neck Surgery,
University of Kansas Medical Center, Kansas City, Kansas
Bruce R. Korf, M.D., Ph.D. Medical Director, Partners Center for Human Genetics,
Associate Professor of Neurology, Harvard Medical School, Boston, Massachusetts
Alan D. Kornblut, M.D., F.A.C.S. Clinical Professor, Department of Otolaryngology,
Georgetown University School of Medicine, Washington, D.C.; and, Adjunct Professor,
Department of Surgery/ Otolaryngology, Uniformed Services University of the Health
Sciences, Bethesda, Maryland
James Allen Koufman, M.D. Staff, North Carolina Baptist Hospital; and, Professor and
Director, Center for Voice Disorders, Department of Otolaryngology, Wake Forest
University School of Medicine, Winston-Salem, North Carlonia
Charles J. Krause, M.D. Taubman Center, Ann Arbor, Michigan
Russell W.H. Kridel, M.D. Facial Plastic Surgery Association, Houston, Texas
Roger Kula, M.D. Chairman, Department of Neurology, Long Island College Hospital;
and, Associate Professor, Clinical Neurology, State University of New York Health
Sciences Center at Brooklyn, Brooklyn, New York
John F. Kveton, M.D. Attending Surgeon, Yale New Haven Hospital; and, Professor,
Department of Surgery and Otolaryngology, Yale University School of Medicine, New
Haven, Connecticut
Ollivier Laccourreye, M.D. Department of OtolaryngologyHead and Neck Surgery,
Laennec Hospital, University of Paris, Paris, France
Anil K. Lalwani, M.D. Assistant Professor, Department of Otolaryngology, University of
CaliforniaSan Francisco, San Francisco, California
Paul R. Lambert, M.D. Professor and Chair, Department of OtolaryngologyHead and
Neck Surgery, Medical University of South Carolina, Charleston, South Carolina
Donald C. Lanza, M.D. Head, Section of Nasal and Sinus Disorders, Department of
Otolaryngology, The Cleveland Clinic Foundation, Cleveland, Ohio
Wayne F. Larrabee, Jr., M.D. Clinical Professor, Department of OtolaryngologyHead
and Neck Surgery and Facial Plastic Surgery, University of Washington, Seattle,
Washington
William Lawson, M.D., D.D.S. Department of Otolaryngology, Mount Sinai Medical
Center, New York, New York
Joseph L. Leach, M.D. Director, Facial Plastic and Reconstructive Surgery, The
University of Texas Southwestern Medical Center; and, Associate Professor,
OtolaryngologyHead and Neck Surgery, Dallas, Texas
Kelvin C. Lee, M.D. ENT Department, University of CaliforniaSan Francisco, San
Francisco, California
James C. Lemon, D.D.S. Associate Professor of Dental Oncology, Department of Head
and Neck Surgery, Section of Oncologic Dentistry and Prosthodontics, The University of
Texas M.D. Anderson Cancer Center, Houston, Texas
Michael Leo Lepore, M.D. Department of OtolaryngologyHead and Neck Surgery,
University of Colorado School of Medicine; and, Division of Otolaryngology, Rose
Medical Center, Denver, Colorado
Paul A. Levine, M.D. Professor and Chair, Department of OtolaryngologyHead and
Neck Surgery, University of Virginia Health System, Charlottesville, Virginia
Jessica W. Lim, M.D. Department of OtolaryngologyBronchoesophagology, Rush-
Presbyterian-St. Lukes Medical Center, Chicago, Illinois
Christopher J. Linstrom, M.D. Associate Professor of Otolaryngology, Department of
Otolaryngology, New York Eye and Ear Infirmary, New York, New York; and, Associate
Professor, Department of OtolaryngologyHead and Neck Surgery, New York Medical
College, Valhalla, New York
Mark C. Littlejohn, M.D. Longview, Texas
James H. Liu, M.D. Clinical Fellow, Department of Pediatric OtolaryngologyHead and
Neck Surgery, Childrens Hospital Medical Center, Cincinnati, Ohio
Jeri A. Logemann, M.D. Ralph and Jean Sundin Professor, Departments of
Communication Sciences and Disorders, Northwestern University; and, Departments of
Neurology and OtolaryngologyHead and Neck Surgery, Northwestern University
Medical School Evanston, Illinois
Frank E. Lucente, M.D. Chairman, Department of Otolaryngology, Long Island College
Hospital, Brooklyn, New York
Charles M. Luetje III, M.D. Otologic Center, Inc., Kansas City, Missouri
Thomas F. Lundeen, M.D. Carolina Oral and Facial Pain Center, Durham, North
Carolina
Rodney P. Lusk, M.D., F.A.C.S., F.A.A.P. Chief, Pediatric Otolaryngology, St. Louis
Childrens Hospital; and, Professor of Otolaryngology, Washington University School of
Medicine, St. Louis, Missouri
Richard L. Mabry, M.D. Professor, Department of Otolaryngology, University of Texas
Southwestern Medical Center, Dallas, Texas
Jose M. Manaligod, M.D. Assistant Professor, Department of OtolaryngologyHead
and Neck Surgery, University of Kentucky Chandler Medical Center, Lexington,
Kentucky
Leila Mankarious, M.D. Assistant Surgeon, Department of Otolaryngology,
Massachusetts Eye and Ear Infirmary; and Assistant Professor, Department of
Otolaryngology, Harvard Medical School, Boston, Massachusetts
J. Douglas Mann, M.D. Department of Neurology, University of North Carolina, Chapel
Hill, North Carolina
Bradley F. Marple, M.D. Chief, Department of Otolaryngology, Parkland Memorial
Hospital; and, Associate Professor, Department of OtolaryngologyHead and Neck
Surgery, University of Texas Southwestern Medical Center, Dallas, Texas
Jack W. Martin, D.D.S. Professor and Chief, Department of Head and Neck Surgery,
Section of Oncologic Dentistry and Prosthodontics, The University of Texas M.D.
Anderson Cancer Center, Houston, Texas
William H. Martin, Ph.D. Director, Tinnitus Clinic, Oregon Hearing Research Center;
and, Professor, Department of Otolaryngology, Oregon Health Sciences University,
Portland, Oregon
Sam Marzo, M.D. Department of OtolaryngologyHead and Neck Surgery, Loyola
University, Maywood, Illinois
Douglas J. Mathisen, M.D. Chief, General Thoracic Surgery, Massachusetts General
Hospital; and, Professor of Surgery, Harvard Medical School, Boston, Massachusetts
Gregory J. Matz, M.D. Professor and Chair, Department of Otolaryngology, Loyola
University Medical Center, Maywood, Illinois
Michael D. Maves, M.D. Attending Staff, Department of OtolaryngologyHead and Neck
Surgery, Georgetown University Medical Center; and, Adjunct Professor, Department of
OtolaryngologyHead and Neck Surgery, Georgetown University School of Medicine,
Washington, D.C.
Thomas V. McCaffrey, M.D., Ph.D. Program Director, H. Lee Moffitt Cancer Center and
Research Institute; and, Professor and Chair, Department of OtolaryngologyHead and
Neck Surgery, College of Medicine, University of South Florida, Tampa, Florida
Becky McGraw-Wall, M.D. Associate Professor and Vice Chairman, Department of
Otolaryngology, University of Texas Medical School, Houston, Texas
Jesus E. Medina, M.D. Professor and Chairman, Department of Otolaryngology,
Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma
William L. Meyerhoff, M.D., Ph.D. Professor, Department of Otolaryngology, University
of Texas Southwestern Medical Center, Dallas, Texas
Andrew J. Miller, M.D. Associate, St. Peters University Medical Center, Edison, New
Jersey
Robert H. Miller, M.D. Dean, University of Nevada School of Medicine, Las Vegas,
Nevada
John H. Mills, Ph.D. Department of Otolaryngology, Medical University of South
Carolina, Charleston, South Carolina
Ron B. Mitchell, M.D. Assistant Professor and Chief of Pediatric Otolaryngology,
Division of Otolaryngology Plastic and Reconstructive Surgery, University of New
Mexico, Albuquerque, New Mexico
Richard T. Miyamoto, M.D., F.A.C.S., F.A.A.P. Professor and Chair, Department of
Otolaryngology, Indiana University Medical School, Indianapolis, Indiana
Brian A. Moore, M.D. Department of OtolaryngologyHead and Neck Surgery,
Vanderbilt University Medical Center, Nashville, Tennessee
Charles M. Myer III, M.D. Department of Pediatric Otolaryngology, Childrens Hospital
Medical Center; and, Professor, Department of OtolaryngologyHead and Neck Surgery,
University of Cincinnati, Cincinnati, Ohio
Eugene N. Myers, M.D. Professor and Eye and Ear Foundation Chair, Department of
Otolaryngology, University of Pittsburgh School of Medicine, The Eye and Ear Institute,
Pittsburgh, Pennsylvania
Jeffrey N. Myers, M.D., Ph.D. Assistant Professor of Surgery, Department of Head and
Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston, Texas
Robert M. Naclerio, M.D. Professor and Chief, Department of OtolaryngologyHead
and Neck Surgery, Pritzker School of Medicine, University of Chicago, Chicago, Illinois
Cherie-Ann O. Nathan, M.D. Department of OtolaryngologyHead and Neck Surgery,
Louisiana State University, Shreveport, Louisiana
H. Bryan Neel III, M.D., Ph.D. Department of Otorhinolaryngology, Mayo Clinic and
Mayo Foundation, Rochester, Minnesota
J. Gail Neely, M.D. Professor and Director of Otology, Neurotology, and Base of Skull
Surgery, Department of OtolaryngologyHead and Neck Surgery, Washington
University School of Medicine, St. Louis, Missouri
Andrew J. Nemechek, M.D. Chief, Section for Head and Neck Cancer, Tulane Cancer
Center; and, Assistant Professor, Department of OtolaryngologyHead and Neck
Surgery, Tulane University School of Medicine, New Orleans, Louisiana
Jeffrey A. Nerad, M.D. Department of Opthamology, University of Iowa Hospitals and
Clinics, Iowa City, Iowa
James L. Netterville, M.D. Assistant Professor, Department of Otolaryngology,
Vanderbilt University Medical Center, Nashville, Tennessee
Mark T. Newcomer, M.D. Department of OtolaryngologyHead and Neck Surgery,
University of Texas Southwestern Medical Center, Dallas, Texas
Shawn D. Newlands, M.D. Assistant Professor, Department of Otolaryngology,
University of Texas Medical Branch at Galveston, Galveston, Texas
Arnold M. Noyek, M.D., F.R.C.S.C. Chairman, CISEPO Program, Department of
Otolaryngology, Mount Sinai Hospital; and, Professor of Otolaryngology, Public Health
Services and Medical Imaging, University of Toronto, Toronto, Ontario, Canada
Patrick J. Oliverio, M.D. Assistant Professor and Neuroradiologist, Department of
Diagnostic Radiology, Georgetown University Medical Center, Washington, D.C.
Terry S. Olson, M.D. Ear, Nose and Throat Specialties, P.C., Lincoln, Nebraska
Randall P. Owen, M.D. Attending Surgeon, Montefiore Medical Center; and, Instructor
of Surgery, Albert Einstein College of Medicine, Bronx, New York
Steven M. Parnes, M.D. Professor and Head, Division of Otolaryngology, Albany
Medical College, Albany, New York
Norman J. Pastorek, M.D. Associate Attending, Department of Otolaryngology, New
York Presbyterian Hospital; and, Clinical Professor and Clinical Director, Department of
Otolaryngology, Cornell Medical College, New York, New York
Nicholas J. Patronas, M.D. Chief, Neuroradiology Section, Diagnostic Radiology
Department, Magnuson Clinical Center, National Institute of Health, Bethesda,
Maryland; and, Professor, Department of Radiology, Georgetown University,
Washington, D.C.
Kevin D. Pereira, M.D. Department of Pediatric OtolaryngologyHead and Neck
Surgery, University of Texas Medical School; and, Chief of Otolaryngology, Lyndon B.
Johnson General Hospital, Houston, Texas
George H. Petti, Jr., M.D. Professor, Department of Surgery, Division of
OtolaryngologyHead and Neck Surgery, Loma Linda University Medical Center,
Loma Linda, California
Catherine Picken, M.D. Department of Otolaryngology, Georgetown University Medical
Center, Washington, D.C.
Bradley P. Pickett, M.D. Director, Division of Otology/Neurotology, Department of
Surgery, University of New Mexico Health Sciences Center, Albuquerque, New Mexico
Patrick G. Pieper, M.D. Clinical Assistant Professor, Department of Otolaryngology
Head and Neck Surgery, University of Southern California, Los Angeles, California
Harold C. Pillsbury III, M.D. Professor and Chief, Department of Surgery, Division of
Otolaryngology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
Robert L. Pincus, M.D. Chief, Department of Otolaryngology, New York
Otolaryngology Group; and, Associate Professor, OtolaryngologyHead and Neck
Surgery, New York Medical College, New York, New York
A. Daniel Pinheiro, M.D., Ph.D. Chief Resident Associate, Department of
Otorhinolaryngology, Mayo Clinic and Mayo Graduate School of Medicine, Rochester,
Minnesota
Christopher Poje, M.D. Attending Physician, Department of Otolaryngology and
Pediatrics, Childrens Hospital of Buffalo/Kaleida Health System; and, Assistant
Professor, Department of Otolaryngology and Pediatrics, State University of New York
at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York
Michael D. Poole, M.D., Ph.D. Department of Otolaryngology, University of Texas
Medical School, Houston, Texas
Gregory N. Postma, M.D. Assistant Professor, Department of Otolaryngology, North
Carolina Baptist Hospital; and, Assistant Professor, Center for Voice Disorders, Wake
Forest University School of Medicine, Winston-Salem, North Carolina
Anna M. Pou, M.D. Assistant Professor, Department of Otolaryngology, University of
Texas Medical Branch, Galveston, Texas
Reza Rahbar, M.D. Department of Otolaryngology and Communication Disorders,
Childrens Hospital; and, Department of Otology and Laryngology, Harvard Medical
School, Boston, Massachusetts
Christopher H. Rassekh, M.D. Assistant Professor and Director, Department of
Otolaryngology, West Virginia University, Morgantown, West Virginia
Daniel J. Ratcliff, M.D. Resident, Department of OtolaryngologyHead and Neck
Surgery, University of Texas Southwestern Medical Center, Dallas, Texas
Elie Edmond Rebeiz, M.D. Chief, Department of Head and Neck Surgery, New England
Medical Center; and, Associate Professor, Department of OtolaryngologyHead and
Neck Surgery, Tufts University, Boston, Massachusetts
Robert L. Reddick, M.D. Chief, Department of Pathology, University Hospital; and,
Chair and Frank M. Townsend Professor, Department of Pathology, University of Texas
Health Science Center, San Antonio, Texas
Michael F. Reed, M.D. Chief Resident in Thoracic Surgery, Massachusetts General
Hospital; and, Clinical Fellow in Surgery, Harvard Medical School, Boston,
Massachusetts
Hilary L. Reeh, M.D. The University of Texas Medical Branch at Galveston, Galveston,
Texas
Anthony J. Reino, M.D., M.S.C. Assistant Professor and Attending Physician, Department
of Otolaryngology, Mount Sinai School of Medicine, New York, New York
Dale H. Rice, M.D. Professor and Chair, Department of OtolaryngologyHead and Neck
Surgery, University of Southern California, Los Angeles, California
William J. Richtsmeier, M.D., Ph.D. Chief, Division of Otolaryngology, Bassett
Healthcare, Cooperstown, New York
Todd A. Ricketts, Ph.D. Assistant Professor, Department of Hearing and Speech
Sciences, Vanderbilt University, Nashville, Tennessee
Henry H. Roenigk, Jr., M.D. Professor, Department of Dermatology, Northwestern
University Medical School, Chicago, Illinois
Peter S. Roland, M.D. Professor and Acting Chairman, Department of Otolaryngology,
University of Texas Southwestern Medical Center, Dallas, Texas
Austin S. Rose, M.D. Resident, Division of OtolaryngologyHead and Neck Surgery,
University of North Carolina Medical Center, Chapel Hill, North Carolina
Richard M. Rosenfeld, M.D., M.P.H. Director, Department of Pediatric Otolaryngology,
Long Island College Hospital; and, Professor of Otolaryngology, State University of New
York Downstate Medical Center, Brooklyn, New York
Michael J. Rutter, F.R.A.C.S. Pediatric Otolaryngologist, Department of Pediatric
Otolaryngology, Childrens Hospital Medical Center; and, Assistant Professor,
University Ear, Nose and Throat Specialists, University of Cincinnati College of
Medicine, Cincinnati, Ohio
Leonard P. Rybak, M.D., Ph.D. Department of Surgery, Southern Illinois University
School of Medicine, Springfield, Illinois
James A. Salata, M.D. Department of OtolaryngologyHead and Neck Surgery, Eastern
Virginia School of Medicine, Norfolk, Virginia
Todd E. Samuelson, M.D. Fort Worth, Texas
Perry M. Santos, M.D. Otologic Medical Clinic, Head and Neck Division, Inc.,
Oklahoma City, Oklahoma
Steven D. Schaefer, M.D., F.A.C.S. Chair, Department of Otolaryngology, New York Eye
and Ear Infirmary; and, Professor and Chair, Department of Otolaryngology, New York
Medical College, New York, New York
Gary L. Schechter, M.D. Professor and Chair, Department of OtolaryngologyHead
and Neck Surgery, Eastern Virginia School of Medicine, Norfolk, Virginia
Alexander J. Schleuning II, M.D. Professor, Department of OtolaryngologyHead and
Neck Surgery, Oregon Health Sciences University, Portland, Oregon
Tammy S. Schumacher, M.S.N, A.P.N.P. Clinical Instructor, Department of
Otolaryngology and Communication Sciences, Medical College of Wisconsin,
Milwaukee, Wisconsin
Bruce A. Scott, M.D. Assistant Clinical Professor, Department of Surgery, Division of
Otolaryngology, University of Louisville School of Medicine, Louisville, Kentucky
Robert W. Seibert, M.D. Arkansas Childrens Hospital, Little Rock, Arkansas
Hadi Seikaly, M.D. Department of Surgery, University of Alberta, Cross Cancer Institute;
and, Associate Clinical Professor, Division of OtolaryngologyHead and Neck Surgery,
Edmonton, Alberta, Canada
Roy Brumby Sessions, M.D. Chairman, Department of OtolaryngologyHead and Neck
Surgery, Beth Israel Medical Center, New York, New York; and, Professor,
OtolaryngologyHead and Neck Surgery, Albert Einstein College of Medicine, Bronx,
New York
Samir Shah, M.D. Chief Resident, Department of Otolaryngology, State University of
New York, Health Science Center at Brooklyn, Brooklyn, New York
Fred F. Shahan, M.D., Pharm.D. San Diego Dermatology and Cosmetic Surgery, Inc., San
Diego, California
Stanley M. Shapshay, M.D., F.A.C.S. Chair, Department of OtolaryngologyHead and
Neck Surgery, New England Medical Surgery Center; and, Professor and Chair,
Department of OtolaryngologyHead and Neck Surgery, Tufts University School of
Medicine, Boston, Massachusetts
William W. Shockley, M.D. Professor, Division of OtolaryngologyHead and Neck
Surgery, University of North Carolina Medical Center, Chapel Hill, North Carolina
Kevin A. Shumrick, M.D. Attending Physician, Department of Otolaryngology,
University Hospital; and, Professor, Department of Otolaryngology, University of
Cincinnati Medical Center, Cincinnati, Ohio
Michael W. Sicard, M.D. Resident, The Bobby R. Alford Department of
OtorhinolaryngologyHead and Neck Surgery, Baylor College of Medicine, Houston,
Texas
Carl E. Silver, M.D. Professor, Department of Surgery and Otolaryngology, Albert
Einstein College of Medicine, Montefiore Medical Center, Bronx, New York
William E. Silver, M.D. Department of Surgery-Otolaryngology, Emory University
School of Medicine, Medical College of Georgia; and, Premier Image Cosmetic and
Laser Surgery, Atlanta, Georgia
Mark I. Singer, M.D. University of CaliforniaSan Francisco, Mount Zion Medical
Center, San Francisco, California
Richard J. H. Smith, M.D. Vice Chair, Department of Otolaryngology, University of
Iowa Hospitals and Clinics; and, Sterba Hearing Research Professor, Department of
Otolaryngology, University of Iowa College of Medicine, Iowa City, Iowa
Richard V. Smith, M.D., F.A.C.S. Director of Clinical Affairs, Department of
Otolaryngology, Montefiore Medical Center; and, Assistant Professor, Department of
Otolaryngology, Albert Einstein College of Medicine, Bronx, New York
Robert A. Sofferman, M.D. Professor of Surgery and Chairman, Division of
OtolaryngologyHead and Neck Surgery, University of Vermont School of Medicine;
and, Fletcher Allen Health Care, Burlington, Vermont
Kweon I. Stambaugh, M.D. Associate Professor of Clinical Surgery, Uniformed
Services, University of Health Sciences, Bethesda, Maryland; and, Cabarrus ENT and
Facial Surgery Center, Concord, North Carolina
James A. Stankiewicz, M.D. Professor and Vice Chair, Department of Otolaryngology,
Loyola University Medical Center, Maywood, Illinois
Robert B. Stanley, Jr., M.D., D.D.S. Department of OtolaryngologyHead and Neck
Surgery, Harborview Medical Center, Seattle, Washington
Wendy B.R. Stern, M.D., Department of OtolaryngologyHead and Neck Surgery,
Tufts University School of Medicine, Boston, Massachusetts.
Carl Rusty Stevens, M.D. Department of Otolaryngology, University of Texas
Medical Branch at Galveston, Galveston, Texas
Michael G. Stewart, M.D., M.P.H. Associate Dean and Professor, Department of
Otolaryngology, Baylor College of Medicine, Houston, Texas
Charles M. Stiernberg, M.D. Professor and Chairman, University of Texas Health
Science Center at Houston, Houston, Texas
Scott P. Stringer, M.D. Residency Program Director, Department of Otolaryngology,
Shands Hospital; and, Professor and Vice Chair, Department of Otolaryngology,
University of Florida, Gainesville, Florida
Chester L. Strunk, M.D. Clinical Assistant Professor of Otolaryngology, Department of
Otolaryngology, University of Texas Medical Branch, Clear Lake Regional Medical
Center, Webster, Texas
Fred J. Stucker, M.D., F.A.C.S. Louisiana State University Health Sciences Center,
Shreveport, Louisiana
Leonard E. Swischuk, M.D. Director, Department of Pediatric Radiology, University
Texas Medical Branch, Childrens Hospital; and, Professor, Department of Radiology
and Pediatrics, University of Texas, Galveston, Texas
Thomas A. Tami, M.D. ENT Department, Univeristy of Cincinnati Medical Center,
Cincinnati, Ohio
Luke K.S. Tan, M.D. Senior Lecturer, Department of OtolaryngologyHead and Neck
Surgery, University of Texas Medical Branch at Galveston, Galveston, Texas
M. Eugene Tardy, Jr., M.D., F.A.C.S. Professor and Director of Clinical Otolaryngology,
Division of Facial Plastic Surgery, University of Illinois, Chicago, Illinois
Sherard A. Tatum, M.D. Director, Central New York Center for Cleft and Craniofacial
Disorders, University Hospital; and, Associate Professor, Division of Facial Plastic
Surgery, State University of New YorkUpstate Medical University, Syracuse, New
York
Theodoros N. Teknos, M.D. Assistant Professor of OtolaryngologyHead and Neck
Surgery and Associate Director of Microvascular Surgery, Department of
Otolaryngology, University of Michigan Hospitals, Ann Arbor, Michigan
David James Terris, M.D. Attending Surgeon, Department of Otolaryngology, Stanford
University Medical Center; and, Associate Professor of Surgery, Department of
OtolaryngologyHead and Neck Surgery, Stanford University, Stanford, California
Lester D.R. Thompson, M.D. Chief, Division of OtorhinolaryngicHead and Neck
Pathology, Armed Forces Insitute of Pathology, Washington, D.C.
Scott W. Thompson, M.D. Assistant Professor, Department of Otolaryngology,
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
Dean M. Toriumi, M.D. Associate Professor, Department of Otolaryngology, University
of Illinois, Chicago, Illinios
John M. Truelson, M.D. Associate Professor, Department of Head and Neck Oncology,
Division of Rhinology and Laryngology, The University of Texas Southwestern Medical
Center at Dallas, Dallas, Texas
Mark L. Urken, M.D. Professor and Chairman, Department of Otolaryngology, Mount
Sinai Medical Center, New York, New York
Daniel L. Van Dyke, Ph.D. Chairman, Department of Medical Genetics, Henry Ford
Hospital; and, Professor, Department of Genetics, Henry Ford Hospital System/Case
Western Reserve University, Detroit, Michigan
Everett E. Vokes, M.D. Director, Section of Hematology/Oncology, and Professor,
Medicine and Radiation, University of Chicago, Chicago, Illinois
Jeffrey T. Vrabec, M.D. Chief, Division of Otology/Neurotology, Department of
Otolaryngology, University of Texas Medical Branch at Galveston, Galveston, Texas
Phillip A. Wackym, M.D., F.A.C.S. Chief, Department of Head and Neck Surgery,
Froedtert and Medical College Hospital; and, Professor and Chairman, Department of
Otolaryngology and Communication Sciences, Medical College of Wisconsin,
Milwaukee, Wisconsin
J. Trad Wadsworth, M.D. Department of OtolaryngologyHead and Neck Surgery,
University of Washington, Seattle, Washington
Regina Paloyan Walker, M.D., F.A.C.S. Staff Physician, Department of Surgery,
Hinsdale Hospital, Hinsdale, Illinois; and, Associate Professor, Department of
Otolaryngology, Loyola University, Maywood, Illinois
Conrad Wall III, Ph.D. Department of OtolaryngologyHead and Neck Surgery,
University of Texas Medical Branch at Galveston, Galveston, Texas
Robert C. Wang, M.D., F.A.C.S. Associate Professor, Department of Surgery, University
of Nevada Medical School, Las Vegas, Nevada
Michael J. Wareing, F.R.C.S. Consultant Otolaryngologist, Department of
OtolaryngologyHead and Neck Surgery, St. Bartholomews Hospital, London, United
Kingdom
Peter C. Weber, M.D., F.A.C.S. Professor and Vice Chair, Department of Otolaryngology,
Medical University of South Carolina, Charleston, South Carolina
Gregory S. Weinstein, M.D. Department of OtorhinolaryngologyHead and Neck
Surgery, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania
Raymond L. Weiss, Jr., M.D. Bay Area ENT, Ocean Springs, Mississippi
Mark C. Weissler, M.D. Joseph P. Riddle Distinguished Professor, Department of
OtolaryngologyHead and Neck Surgery, University of North CarolinaChapel Hill,
Chapel Hill, North Carolina
B-Chen Wen, M.D. Professor, Department of Radiation Oncology, University of Miami
College of Medicine, Iowa City, Iowa
Bruce M. Wenig, M.D. Montefiore Medical Center, Bronx, New York
Marc C. Witte, M.D. Department of Otorhinolaryngology, Mayo Clinic and Mayo
Foundation, Mayo Medical School, Rochester, Minnesota
Ian J. Witterick, M.D., F.R.S.C. Department of Otolaryngology, Mount Sinai Hospital;
Head, Division of Otolaryngology, St. Josephs Health Centre; and, Assistant Professor,
Department of Otolaryngology, University of Toronto, Toronto, Ontario, Canada
Gayle E. Woodson, M.D. Department of OtolaryngologyHead and Neck Surgery,
University of Florida, Gainesville, Florida
Ted Yang, M.D. Assistant Professor, Department of Radiation Oncology, University of
Texas Medical Branch at Galveston, Galveston, Texas
John K. Yoo, M.D. Department of Otolaryngology, University of Texas Medical Branch
at Galevston, Galveston, Texas
Dirk Younker, M.D. Director, Anesthesia Services, The University Hospital; and,
Professor, Department of Anesthesia, University of Cincinnati, Cincinnati, Ohio
Alan R. Yuen, M.D. Assistant Professor, Department of Medicine, Stanford University
Medical Center, Palo Alto, California
Barbara A. Zeifer, M.D. Director of Radiology, New York Eye and Ear Infirmary, New
York, New York; and, Associate Professor, Department of Clinical Radiology, Albert
Einstein College of Medicine, Bronx, New York


DEDICATION
To our patients and to the vision of improved health for all who inhabit our shrinking
world. I am grateful for the opportunity to have led the marvelous efforts of our authors
as they assembled and organized this comprehensive collection of important new medical
information.
May we always keep the needs of our patients foremost in our minds and in our hearts as
we study, learn, and practice the science and art of medicine.
B.J.B.
To our patients, who are our greatest teachers, and to our willingness to ask the same
question again and again until we find an answer that helps these patients.
K.H.C.
Dedicated to my patients who taught me sensitivity, to my teachers who taught me ethical
conduct and to my loving family who taught me the value of passing on my heritage
through giving.
G.B.H.
To health care professionals who have focused their professional lives on the well-being
of their fellow man and continue to work and study toward the goal of improved health
care.
J.T.J.
To the medical students, residents, and fellows in otolaryngology training. It is through
their enthusiasm for acquiring knowledge, their innate curiosity, and their willingness to
question established dogma that we educators are ourselves educated.
R.K.J.
To Dr. Newton D. Fischer who gave me the opportunity to become an otolaryngologist,
who enabled me to pursue an academic career, and who made it possible to become
Chief of OtolaryngologyHead & Neck Surgery well before my time.
H.C.P.
Within the constantly broadening field of otolaryngologyhead and neck surgery, the
fundamental and refined principles of plastic and reconstructive surgery find daily
application in each of our diverse subspecialities. Through the principles of specialty
surgery contained throughout this book, we honor our respected teachers while
attempting to catalyze the education of our students and colleagues for the ultimate
benefit of all patients.
M.E.T.


ACKNOWLEDGMENTS
Even after two previous editions, the planning, organization, and management of an
editorial project of the scope required to produce these two volumes was a daunting task.
Teamwork was necessary to complete all of the essential steps on time and within the
budget, and the efforts of our section editors and associate editors have been remarkable.
This is truly their book, and I sincerely appreciate their determination and insistence on a
final product of the highest possible quality.
I also thank the contributors, who worked under strict deadlines and constant prodding to
submit their final chapters.
Additionally, I want to congratulate Tony Pazos, whose outstanding work from the first
and second editions is the core of the extensive medical illustration program for this
book; and Christine Gralapp, who provided all new illustrations for this third edition with
a style and quality that enhanced the existing artwork. There is no other textbook
published in this field that can boast such a talented and reputable tandem.
Finally, it is difficult to find words to express the sense of gratitude I feel for my long-
time editorial colleagues:
To Margi, my life partner and editorial associate of many years.
To Michelle LaPlante and Kerry Barrett, who helped with the editorial improvements of
this book. As developmental editors, Michelle and Kerry were integral in working with
me and the authors to produce a book of the highest quality on time.
To Marilyn Streck, my administrative assistant, who has provided valuable
communication enhancement, support, and encouragement at every step along the way.
To Kathey Alexander, Jim Merritt, Anne Patterson, Deirdre Marino, and the other fine
professionals at Lippincott Williams & Wilkins who have guided so many of our
decisions along the path to publication.


COLOR PLATES
Head & Neck SurgeryOtolaryngology

COLOR PLATES


COLOR PLATE 1. Rigid Storz endoscopes with 0x,
30x, and 70x objective lenses. (See Fig. 30.4.)



COLOR PLATE 2. Endoscopic view of left nasal cavity
shows septal deviation toward the middle turbinate and
middle meatus. (See Fig. 30.5.)



COLOR PLATE 3. Endoscopic view of right middle
meatus shows purulent secretions due to acute sinusitis.
(See Fig. 30.6.)



COLOR PLATE 4. Endoscopic view of polyps in the
left middle meatus. (See Fig. 30.7.)



COLOR PLATE 5. Oral herpes simplex virus ulceration
with erythematous border. (Courtesy of Dr. Robert O.
Greer.) (See Fig. 46.1.)



COLOR PLATE 6. Desquamative gingivitis showing
diffuse erythematous desquamation and ulceration of the
gingiva. (See Fig. 46.2.)



COLOR PLATE 7. Cicatricial pemphigoid showing
diffuse and patchy erythematous lesions of the attached
gingiva. (Courtesy of Dr. Robert O. Greer.) (See Fig.
46.5.)



COLOR PLATE 8. Pemphigus vulgaris, resulting in
severe desquamation of the palatal (A) and buccal (B)
mucosa. (See Fig. 46.7.)



COLOR PLATE 9. Asymptomatic interlacing white
keratotic striae (Wickham striae) of reticular lichen
planus. (See Fig. 46.9.)



COLOR PLATE 10. Painful erosive lichen planus of the
palate. (See Fig. 46.10.)



COLOR PLATE 11. Soft white plaques of
pseudomembranous candidiasis (thrush). (Courtesy of Dr.
Robert O. Greer.) (See Fig. 46.12.)



COLOR PLATE 12. Angular cheilitis. Candidal
colonization of the oral commissures led to moderately
painful macerated folds. (See Fig. 46.13.)



COLOR PLATE 13. Recurrent aphthous stomatitis. A
minor aphthous ulcer with a central white ulceration is
surrounded by an erythematous halo on the buccal
mucosa. (See Fig. 46.14.)



COLOR PLATE 14. Erythematous and ulcerative
changes of oral epithelium secondary to radiation-
induced mucositis. (Courtesy of Dr. Robert O. Greer.)
(See Fig. 46.15.)



COLOR PLATE 15. Miniplate secured extracorporally
to distal aspect of rib in lollipop fashion with two
bicortical screws. After ensuring proper positioning, the
graft is secured with two or more additional screws
placed bicortically through the ramus. The excess plate
length is then trimmed. (See Fig. 49.10.)



COLOR PLATE 16. After resection, the osteotomized
condyle is repositioned and fixated with a miniplate. The
osteotomized zygoma has been reduced and fixated with
a microplate. (See Fig. 49.12.)



COLOR PLATE 17. Acquired subglottic stenosis due to
intubation. (See Fig. 59.4.)



COLOR PLATE 18. Endoscopic view of
laryngomalacia during expiration. (See Fig. 74.7.)



COLOR PLATE 19. Endoscopic view of
laryngomalacia during inspiration with folding inward of
the epiglottis, shortened aryepiglottic folds, and collapse
of the cuneiform cartilages completely obstructing the
laryngeal introitus. (See Fig. 74.8.)



COLOR PLATE 20. Endoscopic view of a posterior
subglottic hemangioma. (See Fig. 74.9.)



COLOR PLATE 21. Endoscopic view of the same
patient with obstructing laryngeal papillomatosis. (See
Fig. 74.11.)



COLOR PLATE 22. Endoscopic view of complete
tracheal rings. (See Fig. 74.13.)



COLOR PLATE 23. Definitive structures formed by the
cartilaginous components of the various pharyngeal
arches. (See Fig. 77.1.) (From Sadler TW. Langman's
medical embryology, 8th ed. Philadelphia: Lippincott
Williams & Wilkins, 2000, with permission.)



COLOR PLATE 24. Normal left middle meatus (See
Fig. 79.1.)



COLOR PLATE 25. Postoperative view of cavity after
an anterior ethmoidectomy (See Fig. 79.5.)



COLOR PLATE 26. Craniotomy of patient with
epidural abscess secondary to a frontal sinus infection
(See Fig. 79.11.)



COLOR PLATE 27. Histologic section of papilloma,
demonstrating fingerlike projection of nonkeratinized
stratified squamous epithelium and vascularized
connective tissue stroma. (See Fig. 85.1.)



COLOR PLATE 28. Sessile papilloma lesions involving
the true vocal folds. (See Fig. 85.2.)



COLOR PLATE 29. Fetal alcohol syndrome.
Microcephaly, flattened nasal dorsum, and elongated
philtrum. (See Fig. 86.7.)



COLOR PLATE 30. Down syndrome. Microcephaly,
epicanthal folds, and mid-face retrusion. (See Fig. 86.11.)



COLOR PLATE 31. Plexiform neurofibroma of the left
facial nerve of an individual with neurofibromatosis type
I. (See Fig. 86.14.)



COLOR PLATE 32. Superficial hemangioma. A:
Proliferating. B: Involution marked by the color fading to
a dull purple. The area, which is a shiny, crimson, is in
the proliferative phase of growth. (See Fig. 93.1.)
(Courtesy of Department of Dermatology, University of
Texas Medical Branch.)



COLOR PLATE 33. Bluish coloration characteristic of
a deep hemangioma. (See Fig. 93.2.) (Courtesy of
Department of Dermatology, University of Texas
Medical Branch.)



COLOR PLATE 34. Rapid lesion growth at the height
of the proliferative phase results in skin ulceration. (See
Fig. 93.3.) (Courtesy of Department of Dermatology,
University of Texas Medical Branch.)



COLOR PLATE 35. Large, superficial facial
hemangioma in the beard distribution. A deep red color
indicates that the lesion is still in the proliferative phase.
(See Fig. 93.4.) (Courtesy of Department of
Dermatology, University of Texas Medical Branch.)



COLOR PLATE 36. A: Capillary malformation in an
adolescent. B: Capillary malformation in an adult.
Cobblestoning is present. (See Fig. 93.5.) (Courtesy of
Department of Dermatology, University of Texas
Medical Branch.)



COLOR PLATE 37. Nevus flammeus lesion of the
glabella. (See Fig. 93.6.) (Courtesy of Department of
Dermatology, University of Texas Medical Branch.)



COLOR PLATE 38. Blue rubber bleb. (See Fig. 93.7.)
(Courtesy of Department of Dermatology, University of
Texas Medical Branch.)



COLOR PLATE 39. Proptosis. A patient with left-sided
proptosis secondary to a metastatic orbital tumor. (See
Fig. 106.1.)



COLOR PLATE 40. Orbital lymphoma extending under
the conjunctiva of the right eye. (See Fig. 106.3.)



COLOR PLATE 41. An inflamed right eye associated
with idiopathic orbital inflammation. The patient
complained of pain with eye movement and diplopia.
(See Fig. 106.8.).



COLOR PLATE 42. Pleomorphic adenoma. The
histologic appearance shows characteristic epithelial and
mesenchymal elements. (See Fig. 107.2.)



COLOR PLATE 43. Oncocytoma. The histologic
appearance is that of typical plump granular eosinophilic
cells. (See Fig. 107.4.)



COLOR PLATE 44. Low-grade mucoepidermoid
carcinoma. Note the epithelial and glandular elements.
(See Fig. 107.5.)



COLOR PLATE 45. High-grade mucoepidermoid
carcinoma. Note the relative lack of glandular elements.
(See Fig. 107.6.)



COLOR PLATE 46. Adenoid cystic carcinoma,
showing the characteristic histologic appearance with
eosinophilic hyaline stroma and perineural invasion. (See
Fig. 107.7.).



COLOR PLATE 47. Acinic cell carcinoma. Note cells
similar to serous acinar cells and cells with clear
cytoplasm. (See Fig. 107.8.)



COLOR PLATE 48. Factors in determining diagnosis of
odontogenic cysts and tumors. (See Fig. 110.19.)



COLOR PLATE 49. Key anatomic landmarks (A) and
standard terminology (B) useful in nasal anatomy and
surgery, easily identified in fresh cadaver dissection. 1,
Nasal bone; 2, nasomaxillary suture line; 3, ascending
process of maxilla; 4, osseocartilaginous junction
(rhinion); 5, upper lateral cartilage; 6, anterior septal
angle; 7, caudal free edge of upper lateral cartilage; 8,
sesamoid cartilage; 9, piriform margin; 10, alar lobule;
11, lateral crus of alar cartilagelateral portion; 12, lateral crus of alar cartilagecentral
portion; 13, tip-defining point; 14, transitional segment of alar cartilage (intermediate
crus); 15, infratip lobule; 16, columella; 17, medial crural footplate. (See Fig. 173.3.)
(From Tardy ME. RMDUL-Surgical anatomy of the nose. New York: Raven Press, 1990,
with permission.)



COLOR PLATE 50. Additional anatomic landmarks (A)
and standard terminology (B). 1, Nasofrontal suture line;
2, nasal bone; 3, intranasal suture line; 4,
osseocartilaginous junction (rhinion); 5, nasomaxillary
suture line; 6, ascending process of maxilla; 7, levator
labii superioris muscle; 8, transverse nasalis muscle; 9,
cephalic portion of upper lateral cartilage (articulates to
undersurface of nasal bone); 10, piriform margin; 11,
sesamoid cartilages; 12, cartilaginous dorsum; 13, upper lateral cartilage; 14, caudal free
margin of upper lateral cartilage; 15, intercartilaginous ligament; 16, quadrangular
cartilage; 17, anterior septal angle; 18, tip-defining point alar cartilage; 19, lateral crus of
alar cartilage; 20, concavity (hinge) of lateral crus; 21, lateral aspect of lateral crus;
RMDUL-22, alar lobule; RMDUL-23, infratip lobule; RMDUL-24, columella. (See Fig.
173.4.) (From Tardy ME. RMDUL-Surgical anatomy of the nose. New York: Raven
Press, 1990, with permission.)



COLOR PLATE 51. Additional anatomic landmarks of
nose. 1, Apex of alar cartilage; 2, medial angle of dome;
3, lateral angle of dome; 4, alar cartilage transitional
segmentintermediate crus; 5, lateral crus alar cartilage;
6, medial crus alar cartilage; 7, medial crural footplate; 8,
nostril aperture; 9, nostril floor; 10, nostril sill; 11, lateral
alar sidewall; 12, alar lobule; 13, alar-facial junction; 14,
anterior septal angle; 15, caudal septum; 16, maxillary
crest; 17, nasal spine; 18, infratip lobule. (See Fig. 173.5.) (From Tardy ME. RMDUL-
Surgical anatomy of the nose. New York: Raven Press, 1990, with permission.)



COLOR PLATE 52. Proper plane for elevation of the
nasal soft tissues, intimate to the underlying nasal skeletal
framework. The superficial musculoaponeurotic system
(RMDUL-SMAS) layer has been elevated to reveal this
desirable tissue dissection plane. (See Fig. 173.11.) (From
Tardy ME. RMDUL-Surgical anatomy of the nose. New
York: Raven Press, 1990, with permission.)



COLOR PLATE 53. A: The mimetic muscles of
expression influencing the nose exist in a continuous
sheet, interconnected by a thin tendonlike aponeurosis.
The individual muscles are inconstant in their
development and degree of action from patient to patient
but are clearly contributory to the extensive superficial
musculoaponeurotic system (SMAS) layer of tissue,
which distributes and counterbalances motion forces
impacting on the nose. This SMAS layer is largely ignored in standard descriptions of
rhinoplasty technique when, in reality, it plays a vital role in achieving favorable long-
term healing results. Specifically, the SMAS layer provides a continuous, although
variably thick, layer of cushioning over the nasal skeleton, aiding in smooth contouring
and appearance of the nasal epithelial surface (if cut or torn during surgery, the edges
may retract creating bulges, irregularities, and depressions as, during healing, the dermis
adheres directly to the nasal skeleton with no intervening musculoaponeurotic layer).
RMDUL-1a, Transverse nasalis; RMDUL-1b, alar nasalis; RMDUL-2a, medial fascicle
procerus; RMDUL-2b, lateral fascicle procerus; 3, anomalous nasi; 4, dilator naris
anterior; 5, compressor narium minor; 6, levator labii superioris alaeque nasi; 7,
depressor septi nasi; 8, orbicularis oris. B: The SMAS plays an important role in
respiration and nasal rhinoplasty. Synergistic action of the dilator and compressor sets of
nasal muscles, balanced in an interconnected manner by the SMAS layer, alters the
rigidity and transmural pressure of the nasal valve (in ipsilateral facial paralysis, where
this musculoaponeurotic control is unilaterally absent, alar collapse may be witnessed).
Alar collapse on quiet inspiration postrhinoplasty is a common complication, likely due
to excessive resection and sacrifice of supratip SMAS and alar cartilages. (See Fig.
173.13.) (From Tardy ME. RMDUL-Surgical anatomy of the nse. New York: Raven
Press, 1990, with permission.)



COLOR PLATE 54. The paired nasal bones and
attached ascending process of the maxillae compose the
bony framework of the nose. (See Fig. 173.14.) (From
Tardy ME. RMDUL-Surgical anatomy of the nose. New
York: Raven Press, 1990, with permission.)



COLOR PLATE 55. Relationship to the lacrimal crest
of typical lateral osteotomy pathway and sac. (See Fig.
173.17.)



COLOR PLATE 56. Intimate underlapping relationship
of the upper lateral cartilages to the caudal undersurface
of the nasal bones. (See Fig. 173.18.)



COLOR PLATE 57. Cadaver demonstration of distal
margins of upper lateral cartilages departing the septum,
attached by underlying mucoperichondrium. (See Fig.
173.20.) (From Tardy ME. RMDUL-Surgical anatomy of
the nose. New York: Raven Press, 1990, with
permission.)



COLOR PLATE 58. Surgical reduction of the
cartilaginous dorsum commonly requires a greater
reduction of the cartilaginous profile relative to the bony
profile. (See Fig. 173.21.) (From Tardy ME. RMDUL-
Surgical anatomy of the nose. New York: Raven Press,
1990, with permission.)



COLOR PLATE 59. Numerous sesamoid cartilages are
commonly located just lateral to the lateral extension of
the lower lateral cartilage and upper lateral cartilage.
They play essentially no role in reduction rhinoplasty.
(See Fig. 173.22.)



COLOR PLATE 60. Typical anatomy of nasal septum,
demonstrating extensive posterior prolongation of a
tongue of quadrangular cartilage, insinuated between
the perpendicular plate above and vomer below. (See Fig.
173.27.)



COLOR PLATE 61. A circle delineates the alar
cartilages, which create distinct anatomic variations to the
nasal tip anatomy. (See Fig. 173.33.) (From Tardy ME.
RMDUL-Surgical anatomy of the nose. New York:
Raven Press, 1990, with permission.)



COLOR PLATE 62. An intermediate crus joins the
lateral and medial crus of the lower lateral cartilages. If
the intermediate crura (and thus the apex of the domes)
are widely bifurcated, a broad trapezoid appearance to the
tip occurs, as drawn on the left. If the intermediate crura
are closely opposed, a more triangular appearance to the
nasal tip basal anatomy exists. (See Fig. 173.36.)



COLOR PLATE 63. This black patient desired a more
sculpted tip with better projection and a narrower alar
base. A: Preoperative frontal view. B: Preoperative
lateral view. C: Preoperative basal view. D:
Postoperative frontal view. E: Postoperative lateral view.
F: Postoperative basal view. (See Fig. 177.5.)



COLOR PLATE 64. The cross-section on the cadaver
shows the insulating layer of fat that lies directly beneath
the skin. (See Fig. 181.2.)



COLOR PLATE 65. Cadaver dissection shows the
decussation of the platysma muscle fibers across the
midline. (See Fig. 181.5.)



COLOR PLATE 66. This patient had a face-lift,
rhinoplasty, chin augmentation, and malar implants. A:
Preoperative view: patient with flattened malar
prominence and receding chin. B: Postoperative view:
face-lift with chin implant and cheek implant. Notice the
malar prominence and strong chin with shallow
melolabial fold. (See Fig. 184.12.)



COLOR PLATE 67. Chin augmentation alone. A:
Preoperative view: hypoplastic mandible makes the nose
appear prominent. B: Postoperative view: chin implant.
The nose appears to be in better proportion to the rest of
the face. (See Fig. 184.16.)



COLOR PLATE 68. Actinic keratosis. (See Fig. 187.1.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 69. Actinic cheilitis. (See Fig. 187.2.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 70. Cutaneous horn. (See Fig. 187.3.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 71. Seborrheic keratosis (inferior).
Open comedones (superior). (See Fig. 187.4.) (Reprinted
from McKee P, duVivier A. RMDUL-Atlas of clinical
dermatology. London: Gower, 1986; with permission.)



COLOR PLATE 72. Keratoacanthoma. (See Fig. 187.5.)
(Reprinted from McKee P, duVivier A. Atlas of clinical
dermatology. London: Gower, 1986; with permission.)



COLOR PLATE 73. Epidermal cyst. (See Fig. 187.6.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 74. Milia. (See Fig. 187.7.) (Reprinted
from McKee P, duVivier A. RMDUL-Atlas of clinical
dermatology. London: Gower, 1986; with permission.)



COLOR PLATE 75. Trichofolliculoma. (See Fig.
187.8.) (Reprinted from McKee P, duVivier A. RMDUL-
Atlas of clinical dermatology. London: Gower, 1986;
with permission.)



COLOR PLATE 76. Trichoepitheliomas. (See Fig.
187.9.) (Reprinted from McKee P, duVivier A. RMDUL-
Atlas of clinical dermatology. London: Gower, 1986;
with permission.)



COLOR PLATE 77. Multiple trichilemmomas of
Cowden disease. (See Fig. 187.10.) (Reprinted from
McKee P, duVivier A. RMDUL-Atlas of clinical
dermatology. London: Gower, 1986; with permission.)



COLOR PLATE 78. Rhinophyma. (See Fig. 187.11.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 79. Syringomas. (See Fig. 187.12.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 80. Hidrocystoma. (See Fig. 187.13.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 81. Pilomatricoma. (See Fig. 187.14.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 82. Nevus sebaceus. (See Fig. 187.15.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 83. Nevus flammeus (port wine stain).
(See Fig. 187.16.) (Reprinted from McKee P, duVivier A.
RMDUL-Atlas of clinical dermatology. London: Gower,
1986; with permission.)



COLOR PLATE 84. Capillary hemangioma. (See Fig.
187.17.) (Reprinted from McKee P, duVivier A.
RMDUL-Atlas of clinical dermatology. London: Gower,
1986; with permission.)



COLOR PLATE 85. Pyogenic granuloma. (See Fig.
187.18.) (Reprinted from McKee P, duVivier A.
RMDUL-Atlas of clinical dermatology. London: Gower,
1986; with permission.)



COLOR PLATE 86. Nevus araneus. (See Fig. 187.19.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 87. Osler-Rendu-Weber disease
(hereditary hemorrhagic telangiectasia). (See Fig.
187.20.) (Reprinted from McKee P, duVivier A.
RMDUL-Atlas of clinical dermatology. London: Gower,
1986; with permission.)



COLOR PLATE 88. Venous lake. (See Fig. 187.21.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 89. Hypertrophic scar. (See Fig.
187.22.) (Reprinted from McKee P, duVivier A. Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 90. Keloid. (See Fig. 187.23.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 91. Adenoma sebaceum. (See Fig.
187.24.) (Reprinted from McKee P, duVivier A.
RMDUL-Atlas of clinical dermatology. London: Gower,
1986; with permission.)



COLOR PLATE 92. Multiple leiomyomas. (See Fig.
187.25.) (Reprinted from McKee P, duVivier A.
RMDUL-Atlas of clinical dermatology. London: Gower,
1986; with permission.)



COLOR PLATE 93. Neurofibroma. (See Fig. 187.26.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 94. Junctional nevus. (See Fig.
187.27.) (From the Institute for Dermatologic
Communication and Education, 1976; with permission.)



COLOR PLATE 95. Dermal nevi. (See Fig. 187.28.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 96. Compound nevus. (See Fig.
187.29.) (Reprinted from McKee P, duVivier A.
RMDUL-Atlas of clinical dermatology. London: Gower,
1986; with permission.)



COLOR PLATE 97. Spitz nevus. (See Fig. 187.30.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 98. Lentigo senilis. (See Fig. 187.31.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 99. Nevus of Ota. (See Fig. 187.32.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 100. Nevus of Ota involving sclera.
(See Fig. 187.33.) (Reprinted from McKee P, duVivier A.
RMDUL-Atlas of clinical dermatology. London: Gower,
1986; with permission.)



COLOR PLATE 101. Blue nevus. (See Fig. 187.34.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 102. Flat warts. (See Fig. 187.35.)
(Reprinted from McKee P, duVivier A. RMDUL-Atlas of
clinical dermatology. London: Gower, 1986; with
permission.)



COLOR PLATE 103. Molluscum contagiosum. (See
Fig. 187.36.) (From the American Academy of
Dermatology, 1977; with permission.)





PREFACE
Ten years ago we accepted the challenging task of creating a new comprehensive
textbook dealing with the specialty of head and neck surgeryotolaryngology. We are
pleased to report the success of our first two editions, and are enthusiastic about the
additions, improvements, and updated information in this third edition. Since you are
taking the time to read this preface, you are obviously interested in the who, what, and
why of our efforts, so we will share our vision with you in the next few paragraphs.
A group of experienced teacher-surgeons set off on a journey toward the common goal of
creating a learning system that was organized in a new way that would facilitate the
cognitive mastery of our specialty. We have worked together again for two years, and
have also enlisted many new expert authors, in order to fashion the product you are
holding in your hands.
More than a textbookits a learning system, is the phrase we have uttered repeatedly.
What does such a claim mean to you? Why should you believe in our concept or invest in
our work?
To bring this novel idea into being, first and foremost we have sought the most important,
new scientific informationcontent relevant to the fundamental decisions we make in
caring for patients. We have organized this information into a sound educational format
with the following key features:
Consistent and balanced chapter elements
Extensive use of summary tables
Creation of clear new illustrations
Highlight summaries at the end of each chapter for emphasis
The end result is a comprehensive, high-quality two-volume set that is reader friendly,
yet effective in its facilitation of the process by which physicians achieve clinical
competence in a specialty.
We take great pride in the success achieved by our editorial team in attracting many of
the finest authors in each subspecialty category, communicating our vision to them, and
encouraging them to work within our publishing deadlines. The spectacular illustrations
by Tony Pazos and Christine Gralapp have enhanced the written word very effectively
and have clarified the complex subjects to be understood. We have enjoyed working with
the seasoned international support team at Lippincott Williams & Wilkins, who have
helped to refine our initial ideas and expand our understanding of educational psychology
and its interface with modern medical publishing.
We have arrived together once more at the moment when our vision becomes a reality.
Months of teamwork now have been transformed into tangible volumes that are available
for your usefor your further educationtoward the benefits of better care for your
patients.
Some have asked: Do we really need another textbook in this specialty? Yes, we do. I
am even more certain that we need a learning system. We have taken a major step toward
that goal, and we eagerly await your criticism and your suggestions for improvement.
It is an honor to provide these thoughts on behalf of this illustrious editorial team of head
and neck surgeonsotolaryngologists. We welcome your decision to embark with us on
this journey toward a higher level of medical understanding.
Byron J. Bailey, M.D., F.A.C.S.

1 SURGICAL ANATOMY OF THE HEAD AND NECK
Head & Neck SurgeryOtolaryngology
1




SURGICAL ANATOMY OF THE HEAD AND NECK
SUSAN D. JOHN
MICHAEL D. MAVES

Susan D. John: Pediatric Radiology Section, Memorial/Hermann Children's Hospital; Department of
Radiology, University of TexasHouston Medical School, Houston, Texas.
M.D. Maves: Department of Otolaryngology, Georgetown University Medical Center and School of
Medicine, Washington, D.C.


The Cranium
Scalp
Calvaria
Cranial Fossae
Eyelid, Orbit, and Eye
Eyelids
Tarsus
Blood Supply
Lacrimal System
Orbit
Eye
The Ear
Nose and Paranasal Sinuses
External Nose
Nasal Cavity
Sinuses
Ethmoid Sinuses
Sphenoid Sinus
Maxillary Sinus
The Face
Facial Bones and Muscles
Parotid Gland
Facial Nerve
Oral Structures
Maxilla
Palate
Mandible
Hyoid Bone and Tongue
Submandibular Gland
Pharynx and Larynx
Nasopharynx
Oropharynx
Hypopharynx
Larynx
The Neck
Cervical Triangles
Inferior Portion of the Neck
Lateral Portion of the Neck
Arterial Supply
Venous Supply
Lymphatic Vessels
Viscera
Bibliography
Anatomy is the basic science of all surgery. Surgery in the region of the head and neck
cannot be considered safe unless the surgeon thoroughly understands the anatomy of this
area and its important variations. Although anatomic structures and the relations between
them do not change, our knowledge of anatomy must be continually updated to meet the
challenge of new surgical techniques and approaches. This chapter is overview of
surgical anatomy of the head and neck with a focus on the major regions. It is not a
substitute for thorough anatomic knowledge, which can be gained only through intensive
study in a cadaver laboratory and an operating room.
THE CRANIUM
Scalp
The cranium is covered by the hair-bearing scalp, which is divided into layers of skin and
subcutaneous tissue, galea aponeurotica, loose connective tissue, and periosteum or
pericranium covering the calvarial vault. The blood supply of the scalp comes from the
paired supraorbital and supratrochlear arteries anteriorly, the terminal branches of the
superficial temporal arteries laterally, and the occipital vessels posteriorly. This rich
vascularity provides a network on which small scalp flaps can be based and rotated, as in
the management of male pattern baldness. Sensation to the scalp is provided by branches
of cranial and spinal nerves.
Calvaria
The bony vault of the cranium, the calvaria, consists of the unpaired frontal bone, the
paired parietal bones, and the unpaired occipital bone (Fig. 1.1). In the lateral aspect, the
greater wing of the sphenoid bone and the temporal bone complete the cranium. There is
a rich layer of diploic bone between the inner and outer tables of the calvaria. This is a
source for split-thickness calvarial bone grafts, which often are used in head and neck
reconstruction. The calvarium is thickest at the external occipital protuberance and in the
parietal region. It is thinnest over the temporal region. This allows ready access for
neurotologic operations on the middle fossa. The venous circulation of the calvaria is
provided by diploic veins, which drain to the veins of the scalp or into the dural venous
sinuses. In some instances the diploic veins are connected to each other, and this
communication allows osteomyelitis that originates in the frontal sinus to involve the
frontal bone, scalp, and dura.

FIGURE 1.1. Scalp, cranium, and intracranial cavity. A:
1, Coronal suture; 2, superior temporal line; 3, inferior
temporal line; 4, os parietale; 5, squamous suture; 6,
parietomastoid suture; 7, lambdoid suture; 8, occipital
bone; 9, occipitomastoid suture; 10, mastoid process; 11,
external acoustic meatus; 12, styloid process; 13, condyle
of mandible; 14, coronoid process of mandible; 15, body
of mandible; 16, mental foramen; 17, zygomatic bone;
18, infraorbital foramen; 19, frontal process (maxilla); 20, anterior nasal spine; 21, nasal
bone; 22, lacrimal bone; 23, orbital lamina of ethmoid bone; 24, glabella; 25, sphenoid
bone; 26, pterion; 27, temporal bone. B: 1, Sphenoid bone; 2, frontal bone; 3, anterior
cranial fossa; 4, anterior clinoid process; 5, carotid sulcus; 6, middle cranial fossa; 7,
petrous portion of temporal bone; 8, internal acoustic meatus; 9, jugular foramen; 10,
mastoid foramen; 11, hypoglossal canal; 12, foramen magnum; 13, posterior cranial
fossa; 14, sulcus for greater and lesser petrosal nerves; 15, foramen spinosum; 16,
foramen ovale; 17, foramen lacerum; 18, foramen rotundum; 19, superior orbital fissure;
20, optic canal; 21, anterior ethmoidal foramen; 22, anterior ethmoidal foramen; 23,
foramen cecum.



Cranial Fossae
The intracranial cavity is roughly divided into three fossae. The anterior or frontal cranial
fossa contains the paired frontal lobes and provides access to the nasal cavity for the
olfactory nerves through the cribriform plate. The crista galli provides superior midline
extension of the nasal septum. The middle cranial fossa contains the temporal lobes. In
this important junction of the cranial cavity, the middle meningeal artery arises from the
foramen spinosum, and the trigeminal nerve enters through the superior orbital fissure
(V1), the foramen rotundum (V2), and the foramen ovale (V3). Cranial nerves II, III, IV,
and VI, which traverse the cavernous sinus and enter the orbit, also course through the
middle cranial fossa. The internal carotid artery is in its place in the carotid siphon as it
traverses the cavernous sinus in this region. The posterior cranial fossa contains the
paired cerebellar hemispheres and the brainstem. In this location, the internal auditory
meatus is associated with the seventh and eighth cranial nerve complex. The jugular
foramen, transverse sinus, and foramen magnum are the major landmarks of the posterior
cranial fossa.
EYELID, ORBIT, AND EYE
Eyelids
The upper and lower eyelids are similar in structure, although the upper eyelid is more
mobile and has features not found in the lower eyelid. The space between the eyelids is
known as the palpebral fissure, which is limited medially and laterally by the canthi. At
the medial canthus is the lacrimal caruncle, where there is a small lake of tears and the
tiny papillae of the lacrimal duct system. The conjunctiva is a thin mucous membrane
layer that covers the inner aspects of the eyelids and extends onto the surface of the
globe.
Tarsus
The upper tarsal plate provides rigidity to the upper eyelid and is larger than the lower
tarsus (Fig. 1.2). Each eyelid consists from without inward of skin, subcutaneous tissue,
voluntary muscle of the orbicularis oculi, orbital septum, tarsus, smooth muscle, and
conjunctiva. The more freely mobile upper lid receives the insertion of the levator
palpebrae superioris muscle. The orbicularis oculi is the sphincteric muscle of the upper
and lower eyelids. It attaches at a medial palpebral ligament and spreads in an arc
laterally and inferiorly to provide a sphincteric muscle to the eye. It receives innervation
from the temporal and zygomatic branches of the facial nerve. This muscle interdigitates
with the frontalis muscle and the corrugator supercilia.

FIGURE 1.2. Eyelids and external adnexa. A: 1,
Superior tarsus; 2, levator palpebrae superioris muscle; 3,
supraorbital artery and nerve; 4, supratrochlear artery and
nerve; 5, lacrimal caruncle; 6, superior lacrimal papilla
and puncta; 7, bulbar conjunctiva over sclera; 8, pupil; 9,
cornea; 10, superior palpebral conjunctiva; 11, inferior
palpebral conjunctiva; 12, inferior lacrimal papilla and
puncta; 13, maxilla; 14, lacrimal sac; 15, medial palpebral
ligament; 16, infraorbital foramen; 17, orbital septum; 18, inferior tarsus; 19, orbicularis
oculi muscle (cut); 20, lateral palpebral ligament. B: 1, Orbicularis oculi muscle; 2,
orbital septum; 3, levator palpebrae superioris muscle; 4, superior tarsal muscle (Mller
muscle); 5, superior conjunctival fornix; 6, orbicularis oculi muscle (palpebral portion);
7, superior tarsus; 8, tarsal glands; 9, palpebral conjunctiva; 10, inferior tarsus; 11, sclera;
12, choroid; 13, retina; 14, lens; 15, iris; 16, anterior chamber; 17, cornea.



Blood Supply
The arterial supply of the eyelids is provided by the angular branch of the facial artery,
which forms an anastomotic network with the supraorbital and supratrochlear artery and
shares a small contribution from the superficial temporal vessels. The veins of the eyelids
are larger and more numerous than are the arteries and drain into the ophthalmic and
angular veins medially and the superficial temporal vein laterally. Accompanying the
peripheral arterial arcade of the upper eyelid, the veins of the small venous plexus drain
into the ophthalmic vein, which drains posteriorly to the cavernous sinus. The veins in
this region of the face do not have valves and may propagate septic emboli posteriorly.
This is a particularly dangerous situation for patients who have infections in the areas of
the eyelids or periorbital abscess. These patients are at risk of cavernous sinus
thrombosis.
Lacrimal System
The lacrimal apparatus consists of a secretory portion, the lacrimal gland, its ducts, the
drainage apparatus, the lacrimal canaliculi and sac, and the nasolacrimal duct (Fig. 1.3).
The lacrimal gland is partially divided into two portions by the lateral horn of the
aponeurosis of the levator palpebrae. The larger orbital portion of the gland lies in a
shallow fossa on the frontal bone and is in contact anteriorly with the orbital septum. The
excretory ductules of the lacrimal gland run through the orbital part of the gland, run
through or close to the posterior part of the palpebral portion, and are joined by ducts
from this portion. Removal of the palpebral portion can destroy the drainage of the entire
gland.

FIGURE 1.3. Lacrimal apparatus and drainage system. 1,
Lacrimal gland and ducts; 2, superior lacrimal papilla and
puncta; 3, lacrimal caruncle; 4, lacrimal sac; 5, inferior
lacrimal papilla and puncta; 6, middle nasal concha; 7,
inferior nasal concha; 8, opening of nasolacrimal duct.



Movement of the eyelid distributes tears over the surface of the eye, and any excess tends
to accumulate in the lacrimal lake. This structure drains into the paired superior and
inferior canaliculi and from there into the lacrimal sac. The lacrimal sac is housed in the
bony lacrimal fossa of the medial orbital wall. This drains into the nasal lacrimal duct and
eventually into the inferior meatus of the nose.
Orbit
The bony orbit consists of the medial wall occupied largely by the ethmoid bone, lacrimal
bone, and a portion of the nasal process of the maxilla (Fig. 1.4). The floor of the orbit
consists of the roof of the maxilla. The inferior orbital fissure is at its lateral extent. The
zygomatic bone and greater wing of the sphenoid form the lateral orbital wall and join the
frontal bone superiorly to complete the pyramidal bony orbit. On its medial aspect are the
paired ethmoidal foramina, which provide a route to the orbit for the anterior and
posterior ethmoidal arteries. The optic canal posteriorly transmits the optic nerve and
ophthalmic artery. The superior orbital fissure transmits cranial nerves III, IV, V, and VI
and provides an aperture for the ophthalmic vein.

FIGURE 1.4. Bony orbit.



Eye
The eye consists of the cornea and sclera in the anterior aspect. The anterior chamber
protrudes as a second sphere on the structure of the orbit. The lens and iris form the
posterior portion of the anterior chamber. Contained within the substance of the eye is the
vitreous. The retina rests on the choroid. The fovea centralis is the focal point of the eye.
Asymmetric to the structure of the orbit is the insertion of the optic nerve and ciliary
arteries.
The seven voluntary muscles of the orbit are the levator palpebrae superioris; the
superior, inferior, medial, and lateral rectus muscles; and the superior and inferior oblique
muscles (Fig. 1.5). The smooth muscles of the orbit are the orbitalis muscle, the superior
and inferior tarsal muscles, and ciliary and iridial muscles within the eye. The superior
oblique is supplied by cranial nerve IV, the lateral rectus by cranial nerve VI, and the
other voluntary muscles of the orbit by cranial nerve III. The tarsal and orbital muscles
(of Mller) are supplied by sympathetic fibers derived from the carotid plexus and from
the superior cervical ganglion. The dilator pupillae, the sphincter pupillae, and the ciliary
muscle are supplied by parasympathetic fibers through the oculomotor nerve (III).

FIGURE 1.5. Eye muscles. 1, Levator palpebrae
superioris muscle; 2, superior oblique muscle; 3, superior
rectus muscle; 4, optic nerve; 5, lateral rectus muscle; 6,
inferior rectus muscle; 7, inferior oblique muscle; 8,
medial rectus muscle; 9, trochlea; 10, annular tendon.



The primary blood supply to the orbit is through the ophthalmic artery. The primary
drainage is through the ophthalmic vein, which drains directly into the cavernous sinus.
An additional anastomotic network is present on the anterior aspect of the face in the
form of an arcade of vessels around the eyelids and through the pterygoid plexus.
THE EAR
The development and the anatomic and physiologic features of the ear are discussed in
Chapter 128 and Chapter 129.
NOSE AND PARANASAL SINUSES
External Nose
The external part of the nose is a roughly pyramidal shape. The skeleton of the external
nose is partly bony and partly cartilaginous and membranous. The nasal bones, which are
usually narrow and thicker above, wider and thinner below, articulate firmly above with
the nasal part of the frontal bone and with each other laterally with the nasal process of
the maxilla (Fig. 1.6). Attached to the inferior aspect of the nasal bones are the upper
lateral cartilages. These are continuous with the cartilaginous septum. In the inferior
aspect, the lobule of the nose is formed mostly by the lower lateral cartilages, which
consist of a medial and lateral crus. There are several small cartilages within the nasal
ala. The chief arterial supply of the nose is from the facial artery through the angular
artery and superior labial arteries. Venous drainage is similar, with a component gaining
access to the ophthalmic vein through draining vessels from the trochlear and angular
veins.

FIGURE 1.6. Bony and cartilaginous anatomic
configuration of the external nose.



Nasal Cavity
The nasal cavities are also known as the nasal fossae. The nasal septum consists of the
nasal septal cartilage, the nasal crest of the maxilla, the nasal crest of the palatine bone,
the vomer, and the perpendicular plate of the ethmoid bone. The lateral nasal wall is
formed by the prominent nasal turbinates. The meatus are situated below the
corresponding turbinates (Fig. 1.7). The inferior meatus provides drainage for the
nasolacrimal duct. The middle meatus provides drainage for the anterior nasal sinuses,
namely the frontal sinus, anterior ethmoid sinuses, and the maxillary sinus. The superior
meatus provides drainage for the posterior sinuses, namely the posterior ethmoid and
sphenoid sinuses.

FIGURE 1.7. A: Lateral nasal wall. 1, Frontal sinus; 2,
middle nasal concha; 3, middle nasal meatus; 4, agger
nasi; 5, atrium of middle nasal concha; 6, limen; 7,
vestibule; 8, inferior nasal meatus; 9, incisive canal; 10,
palatine process of maxilla; 11, soft palate; 12,
pharyngeal recess; 13, eustachian tube orifice; 14, toris
tubarius; 15, adenoid; 16, sphenoid sinus; 17, sphenoid
sinus opening; 18, sphenoethmoidal recess; 19, inferior
nasal concha; 20, superior nasal meatus; 21, superior nasal concha; 22, palatine bone. B:
Nasal septum. 1, Perpendicular plate; 2, cribriform plate; 3, crista galli; 4, frontal bone; 5,
nasal bone; 6, septal cartilage; 7, medial crus; 8, anterior nasal spine; 9, incisive canal;
10, palatine process; 11, perpendicular plate; 12, postnasal spine; 13, horizontal plate; 14,
lateral pterygoid plate; 15, medial pterygoid plate; 16, sphenoid sinus; 17, crest; 18, body.



The arterial supply of this region is from internal carotid sources through the anterior and
posterior ethmoid arteries and from an external carotid source through the sphenopalatine
artery. Contributions also may exist from the greater palatine vessels and the septal
branch of the superior labial artery. These form an important anastomotic network in the
anterior septum known as the Kiesselbach plexus, which accounts for most nosebleeds.
Sinuses
The paranasal sinuses consist of the paired frontal, ethmoid, maxillary, and sphenoid
sinuses (Fig. 1.8). The frontal sinus develops as one of several outgrowths from the
region of the frontal recess. Two, three, or even more frontal sinuses on a side have been
reported, and some persons have no frontal sinus. The degree of pneumatization of the
frontal sinuses varies. Pneumatization may extend into the roof of the orbit and laterally
into the frontal bone as far as the sphenoid wing. The frontal sinuses drain into the
anterior aspect of the middle meatus.

FIGURE 1.8. Paranasal sinuses. 1, Nasal septum; 2,
frontal sinus; 3, nasal cavities; 4, ethmoidal cells; 5,
middle nasal concha; 6, middle nasal meatus; 7, maxillary
sinus; 8, inferior nasal concha; 9, hard palate.



Ethmoid Sinuses
The ethmoid sinuses consist of a variable number of separate cavities that honeycomb the
ethmoid bone between the upper part of the lateral nasal wall and the medial wall of the
orbit. The anterior ethmoid cells are divided into frontal recess cells, which open into the
frontal recess of the middle meatus; infundibular cells, which open into the ethmoid
infundibulum; and bullar or middle ethmoid cells, which open directly into the middle
meatus on or above the ethmoid bulla. There may be one to seven posterior ethmoid cells.
The bullae and posterior ethmoid cells may encroach on each other and overlap, the
bullar cells spreading backward or the posterior cells forward. The posterior ethmoid
cells drain into the superior meatus.
Sphenoid Sinus
The sphenoid sinus usually opens into the sphenoethmoidal recess above and behind the
superior nasal concha. The ostium usually is in the posterior wall of the recess, but
sometimes it is on its lateral wall. The degree of pneumatization of the sphenoid sinus
varies. This variation is an important factor in surgical approaches to the pituitary gland.
The relations of the sphenoid sinus are important because of the surrounding anatomic
structures. The optic nerves are superior to the sinus, and the internal carotid artery is
lateral to the sinus within the cavernous sinus. The maxillary nerve lies in the inferior
lateral portion of the sinus in the anterior aspect. The hypophysis lies within the posterior
superior portion of the sphenoid sinus and can be approached through transsphenoidal
hypophysectomy.
Maxillary Sinus
The maxillary sinus usually is the largest of the paranasal sinuses and is situated in the
body of the maxilla. Its anterior wall is the facial surface of this bone, and its posterior
wall is the infratemporal surface. Its medial wall is that of the nasal cavity. The roof of
the maxillary sinus is also the floor of the orbit, and it also may be affected in blowout
fractures of the orbit. The maxillary sinus drains into the middle meatus of the nasal
cavity. The roots of the posterior molar teeth may extend into the sinus. The maxillary
sinus is bounded posteriorly by the pterygomaxillary fossa, through which course the
terminal branches of the internal maxillary artery. These vessels can be approached
through the maxillary sinus for relief of epistaxis.
THE FACE
Facial Bones and Muscles
The bones of the face include the frontal and nasal bones and the facial bones proper
maxilla, mandible, zygomatic, and palatine bones. The facial and mimetic muscles are
divided into five chief groups concerned with the mouth, nose, orbit, ear, and scalp (Fig.
1.9). The platysma muscle in the neck also belongs to the facial group. The chief action
of these muscles is on skin into which they insert. All these muscles are innervated by the
facial nerve.

FIGURE 1.9. Facial muscles. 1, Galea aponeurotica; 2,
frontalis; 3, procerus; 4, depressor supercilii; 5,
corrugator supercilii; 6, orbicularis oculi; 7, nasalis; 8,
levator labii superioris; 9, levator anguli oris; 10, levator
labii superioris alaeque nasi; 11, orbicularis oris; 12,
mentalis; 13, depressor labii inferioris; 14, depressor
anguli oris; 15, platysma; 16, masseter; 17, zygomaticus
major; 18, zygomaticus minor; 19, temporalis; 20, lateral
pterygoid; 21, medial pterygoid; 22, buccinator.



Parotid Gland
The parotid gland, which is anterior to and below the lower part of the ear, extends
subcutaneously backward over the anterior portion of the sternocleidomastoid muscle,
forward over the masseter muscle, and deeply behind the ramus of the mandible to lie
between the mandible and the external acoustic meatus and mastoid process (Fig. 1.10).
The gland is roughly divided into a lateral and medial portion by the course of the facial
nerve. Related to the parotid gland are several periparotid and intraparotid lymph nodes,
which may swell. The parotid gland drains through the parotid duct. It is innervated by
the auriculotemporal nerve from the otic ganglion.

FIGURE 1.10. Parotid gland and facial nerve. 1,
Temporal branch; 2, zygomatic branch; 3, buccal branch;
4, masseter muscle; 5, marginal mandibular branch; 6,
anterior digastric muscle; 7, cervical branch; 8, parotid
gland; 9, posterior digastric muscle; 10, seventh cranial or
facial nerve; 11, pes anserinus.



Facial Nerve
The anatomic characteristics of the facial nerve vary in the extracranial portion of the
nerve. Identification of the nerve depends on marking the position of the posterior belly
of the digastric muscle, the external meatal cartilage, the tympanomastoid suture line, and
the styloid process.
ORAL STRUCTURES
Maxilla
The maxilla is the chief component of the upper jaw (Fig. 1.11). In addition to housing
the dental apparatus and the maxillary sinus, it is related posteriorly to the medial and
lateral pterygoid plates. The hard palate unites the paired maxilla and forms the bony roof
of the oral cavity. Sensation to the upper teeth is provided by the maxillary nerve through
the posterior superior and anterior superior alveolar nerves. The infraorbital nerve,
another branch of V2, provides sensation over the face of the maxilla and soft tissues.

FIGURE 1.11. Maxilla and jaw. A: 1, Sphenopalatine
artery; 2, posterior lateral nasal artery; 3, posterior septal
arteries; 4, anastomosis in the incisive canal; 5, greater
palatine artery; 6, lesser palatine artery; 7, descending
palatine artery; 8, superior alveolar arteries; 9, artery of
the pterygoid canal; 10, anterior and posterior deep
temporal arteries; 11, accessory meningeal artery; 12,
middle meningeal artery; 13, anterior tympanic artery; 14,
deep auricular artery; 15, auriculotemporal nerve; 16, superficial temporal artery; 17,
buccal artery; 18, masseteric artery; 19, inferior alveolar artery; 20, ascending pharyngeal
artery; 21, ascending palatine artery; 22, tonsillar artery; 23, external carotid artery; 24,
facial artery; 25, superior constrictor muscle. B: D, Digastric muscle (cut); M, mylohyoid
artery and nerve; IA, inferior alveolar artery and nerve; LA, lingual artery; L, lingual
nerve; MPT, medial pterygoid muscle and artery; A, angular artery; ST, supratrochlear
artery; SO, supraorbital artery; LPT, lateral pterygoid muscle; SL, sphenomandibular
ligament; O, ophthalmic artery.



Palate
The palate intervenes between the nasal and oral cavities (Fig. 1.12). It consists of the
maxilla, the horizontal process of the palatine bone, and the pterygoid plates. Soft tissues
covering this area form the hard and soft palates of the roof of the mouth. The skeletal
core of the soft palate is the palatine aponeurosis. The most superficial muscle fibers on
the pharyngeal surface of the soft palate are those of the palatopharyngeus muscle. The
levator veli palatini, tensor veli palatini, and uvular muscle complete the structures of the
soft palate.

FIGURE 1.12. Palate. 1, Veli palati muscles; 2, greater
palatine foramina; 3, lesser palatine foramina; 4,
pterygoid hamulus; 5, superior pharyngeal constrictor
muscle; 6, pterygomandibular raphe; 7, buccinator
muscle; 8, palatopharyngeus muscle; 9, palatoglossus
muscle; 10, uvula; 11, palatine tonsil; 12,
palatopharyngeal arch; 13, uvular muscle; 14,
palatoglossal arch; 15, palatine glands; 16, greater
palatine artery and nerve; 17, lesser palatine artery and nerve; 18, salpingopharyngeus
muscle; 19, levator veli palatini muscle; 20, tensor veli palati muscle; 21, pharyngobasilar
fascia; 22, cartilaginous auditory tube; 23, carotid canal; 24, vallate papillae; 25, incisive
foramen.



Mandible
The mandible, or lower jaw, consists of the tooth-bearing body and the ramus that
extends upward from the angle of the mandible. The ramus, including the angle, is
covered externally by the masseter muscle, which is crossed by the facial nerve and
parotid duct. Between the ramus and the medial pterygoid muscle are the inferior alveolar
and lingual nerves. Overlapping the posterior border of the ramus is the parotid gland,
and within and paralleling this border is the upper portion of the external carotid artery.
The superficial branch of this artery emerges from the parotid gland behind the
temporomandibular joint, and its internal maxillary branch runs transversely deep to the
ramus. Inferiorly and medially, the angle and posterior part of the body of the mandible
are related to the submandibular gland, and medially, the anterior part of the mandible is
adjacent to the sublingual glands. The musculature most intimately concerned with the
mandible and its movements consists of the masseter, temporal, and two pterygoid
muscles (Fig. 1.9). These muscles govern mastication and are innervated by the third
division of the trigeminal nerve.
Hyoid Bone and Tongue
The hyoid bone, to which are attached infrahyoid and suprahyoid muscles, effectively
separates the anterior suprahyoid and infrahyoid fascial compartments. The suprahyoid
muscles are the digastric and stylohyoid muscles, the mylohyoid and the geniohyoid
muscles, and the muscles of the tongue (Fig. 1.13). The extrinsic muscles of the tongue
are the genioglossus, the hyoglossus, and the styloglossus. The intrinsic muscles of the
tongue are complicated bundles of interlacing fibers, among which are connective tissue
septa. The midline septum lies between and effectively separates the muscles, nerves, and
vessels of the two sides. It is an almost bloodless midline plane.

FIGURE 1.13. Suprahyoid muscles.



Submandibular Gland
The submandibular gland occupies most of the submandibular triangle and expands
beyond this area over the superficial structures of the anterior and posterior bellies of the
digastric muscle (Fig. 1.14). Its posterior border is close to the lower part of the parotid
gland at the angle of the jaw, where it is separated from this gland by the stylomandibular
ligament. The submandibular gland is crossed superficially by the facial vein and
sometimes by the ramus mandibularis branch of the facial nerve. The larger
submandibular lymph nodes lie along the superficial upper border of the gland, between
it and the mandible. The anterior portion of the submandibular gland lies directly against
the mylohyoid muscle and the mylohyoid nerve. Medial to the mandible and above the
level of the submandibular gland is the lingual nerve in its course toward the tongue.
When the submandibular gland is removed, the facial vein is sacrificed, but the ramus
mandibularis branch of the facial nerve is preserved to avoid disruption of the corner of
the mouth. The facial artery passes across the upper surface of the gland, usually
grooving it deeply before rounding the lower border of the mandible, and must be
sacrificed in removal of the gland. The submandibular and sublingual glands are
innervated from the submaxillary ganglion fibers that accompany the sensory fibers of
the lingual nerve. These fibers originate in the chorda tympani and pass into the
submandibular ganglion.

FIGURE 1.14. Submandibular triangle. 1, Palatoglossus
muscle; 2, lingual nerve; 3, superior constrictor muscle;
4, styloglossus muscle; 5, stylopharyngeus muscle; 6,
hyoglossus muscle (cut); 7, stylohyoid muscle (cut); 8,
external carotid artery; 9, internal jugular vein; 10,
hypoglossal nerve; 11, digastric muscle, anterior belly;
12, geniohyoid muscle; 13, genioglossus muscle; 14,
sublingual artery and vein; 15, submandibular duct; 16,
deep lingual artery and vein; 17, submandibular ganglion; 18, deep lingual artery; 19,
common facial vein; 20, hyoid bone.



PHARYNX AND LARYNX
The wall of the pharynx consists of mucosa and voluntary muscle. The mucosal structure
of the pharynx varies. That of the nasal part is ciliated and resembles the mucosa of the
nose. In the rest of the pharynx, the epithelium is stratified squamous tissue. The
muscular wall of the pharynx with its thin covering of buccal pharyngeal or visceral
fascia is separated from the prevertebral fascia by an area of loose connective tissue that
constitutes the retropharyngeal space.
Nasopharynx
The nasal part of the pharynx, the nasopharynx, is continuous anteriorly through the
choana with the nasal cavities (Fig. 1.15). The floor is the upper surface of the soft palate.
The fornix or roof, the mucosa of which is attached close to the base of the skull, slopes
downward and backward to become continuous with the posterior wall. The eustachian
tubes are prominent on the lateral aspect of the nasal pharynx. There may be adenoid
tissue in the superior recess of the nasopharynx.

FIGURE 1.15. Pharynx. 1, Digastric muscle, posterior
belly; 2, adenoid; 3, pharyngeal raphe; 4, pharyngobasilar
fascia; 5, stylopharyngeus muscle; 6, longitudinal
esophageal muscle; 7, circular esophageal muscle; 8,
posterior cricoarytenoid muscle; 9, cricopharyngeus
muscle; 10, transverse and oblique interarytenoid muscle;
11, inferior constrictor muscle; 12, hyoid bone; 13,
middle constrictor muscle; 14, palatopharyngeus muscle;
15, uvula; 16, superior constrictor muscle; 17, levator veli palati muscle; 18, cartilaginous
auditory tube.



Oropharynx
The oropharynx is continuous anteriorly through the fauces, or oral pharyngeal isthmus,
with the oral cavity. The boundaries of the fauces are the posterior border of the soft
palate above, the palatine arches laterally, and the dorsum of the tongue. Below the
fauces, the anterior wall of the pharynx is the posterior or pharyngeal dorsum of the
tongue. On the posterior parts of the dorsum of the tongue lie irregular nodules of tissue
known as the lingual tonsils. The lateral wall of the passageway of the fauces houses the
large palatine tonsils. The lingual tonsils in the anterior aspect, the palatine tonsils in the
lateral aspect, and the pharyngeal tonsils or adenoids in the posterior and superior aspects
form a ring of lymphoid tissue known as the Waldeyer ring.
Hypopharynx
The laryngeal part of the pharynx, or hypopharynx, extends from just above the level of
the hyoid bone superiorly to the lower border of the cricoid cartilage inferiorly,
narrowing rapidly to become continuous with the esophagus. The anterior wall is formed
laterally by mucosa on the medial surface of the thyroid cartilage and centrally or
medially by the larynx and its appendages. Above is the epiglottis and the aditus of the
larynx. Below the aditus, the anterior wall of the pharynx is also the posterior wall of the
larynx. Lateral to the epiglottis are the lateral glossoepiglottic folds that form the
anterolateral boundary between the oral and laryngeal parts of the pharynx. Below these
folds, the hypopharynx extends forward around the sides of the larynx between this area
and the thyroid cartilage. These bilateral expansions are the piriform recesses or sinuses.
The intrinsic portion of the larynx consists of the epiglottis, false vocal folds, laryngeal
ventricles, paired true vocal folds, and arytenoid cartilages in the posterior aspect.
Contained within the aryepiglottic folds are the paired corniculate and cuneiform
cartilages. The space between the two vocal folds is the glottis.
The muscles of the pharynx are the superior, middle, and inferior constrictors. These
muscles look like ice cream cones inserted into one another. They gradually merge to
form the cricopharyngeus muscle at its inferior extent and then the esophagus. Each
constrictor inserts with the corresponding muscle of the opposite side and the midline
into a posterior midline raphe. These muscles are innervated by cranial nerve X through
the pharyngeal plexus. Dehiscence in the pharyngeal constrictors may give rise to Zenker
diverticula. Immediately lateral to the pharyngeal muscles are the great vessels of the
neck and cranial nerve X.
Larynx
The major structural elements of the larynx are the shield-shaped thyroid cartilage and
cricoid cartilages (Fig. 1.16). They join through the cricothyroid joint. The superior
cornua of the thyroid ala articulate through several small cartilages with the hyoid bone.
Overlying the structure of this skeletal framework are the infrahyoid muscles, which
include the paired sternohyoid, sternothyroid, omohyoid, and thyrohyoid muscles.

FIGURE 1.16. Larynx.



The epiglottis is formed of fibroelastic cartilage and has multiple perforations that allow
free access of lymphatic drainage or tumor to the preepiglottic space. The preepiglottic
space is a C-shaped space bounded superiorly by the median glossoepiglottic ligament,
inferiorly by the thyroid cartilage, anteriorly by the thyrohyoid membrane, and
posterolaterally by the epiglottis and aryepiglottic folds. Free dissemination of tumor can
occur within the preepiglottic space. The paired arytenoid cartilages provide an
attachment for the vocal ligament and movement of the vocal folds. The intrinsic muscles
of the larynx are innervated by the recurrent laryngeal nerve. The exception is the
cricothyroid muscle, which is innervated by the superior laryngeal nerve. The recurrent
laryngeal nerve enters inferiorly and laterally to the cricothyroid articulation through the
Killian-Jamieson area. The recurrent laryngeal nerve on the left originates over the aortic
arch and ascends in the neck to innervate the larynx. On the right, this structure goes
around the subclavian artery.
THE NECK
Cervical Triangles
The prominent landmarks of the neck are the hyoid bone, the thyroid cartilage, the
trachea, and the sternocleidomastoid muscles (Fig. 1.17). The sternocleidomastoid
muscles divide each side of the neck into two major triangles, anterior and posterior. The
anterior triangle of the neck may be further delimited by the strap muscles into the
superior and inferior carotid triangles. The posterior triangles or lateral triangles of the
neck are formed by the posterior border of the sternocleidomastoid muscle anteriorly, the
clavicle inferiorly, and the anterior border of the trapezius muscle posteriorly. The
omohyoid muscle divides this triangle of the neck into a small inferior subclavian triangle
and a larger posterior occipital triangle. Deep to these muscles are the scalenes, which
form much of the muscle mass of the posterior and lateral portions of the neck. The
brachial plexus and subclavian artery course between the anterior and middle scalene
muscles. The subclavian vein courses anteriorly to the anterior scalene muscle.

FIGURE 1.17. Muscles and triangles of the neck. S,
Scalene muscle; M, masseter.



Inferior Portion of the Neck
In the inferior root of the neck and closely associated with the brachial plexus are the
paired phrenic nerves that course medially to innervate the diaphragm (Fig. 1.18). These
nerves originate in the ventral rami of the cervical plexus of the third, fourth, and fifth
cervical nerve rootlets. The subclavian artery gives rise to the thyrocervical trunk. The
transverse cervical and suprascapular arteries typically course laterally over the surface of
the phrenic nerve. This relation allows identification of these structures. The vagus nerve
lies further medially and is contained within the carotid sheath. It shares the sheath with
the common, internal, and external carotid arteries and jugular vein. Posterior to the
carotid sheath lies the cervical sympathetic nerve. On the surface of the carotid sheath lie
the ansa hypoglossi nerves.

FIGURE 1.18. Root of neck. 1, Stylohyoid muscle; 2,
hypoglossal nerve (cranial nerve XII); 3, digastric
muscle; 4, parotid gland; 5, sternocleidomastoid muscle;
6, greater auricular nerve; 7, lesser occipital nerve; 8,
ventral ramus (C2); 9, ventral ramus (C3); 10, accessory
nerve (cranial nerve XI); 11, ventral ramus (C5); 12,
anterior scalene muscle; 13, phrenic nerve; 14, brachial
plexus; 15, subclavian artery and vein; 16, thyrocervical
trunk; 17, vagus nerve; 18, inferior root ansa cervicalis; 19, superior root ansa cervicalis;
20, superior thyroid artery.



Lateral Portion of the Neck
The dominant structure of the lateral cervical triangle is the spinal accessory nerve. It
emanates from the posterior border of the sternocleidomastoid muscle in close
association with the splay of nerves of the cervical sensory plexus. It innervates the
trapezius muscle on its inferior aspect in close association with the transverse cervical
artery or suprascapular artery, which variably supplies the trapezius muscle.
Arterial Supply
The two common carotid arteries differ in length because the right carotid usually arises
from the brachycephalic artery behind the sternoclavicular joint, and the left arises from
the arch of the aorta (Fig. 1.19). Both arteries end by bifurcating into the internal and
external carotid arteries. Over the lateral aspect of these arteries course the paired
hypoglossal nerves. The internal carotid artery is situated more posteriorly and has no
branches. The external carotid artery has branches and lies slightly anteriorly. This
information can be crucial in differentiating the two vessels for ligation. From its origin,
the internal carotid artery ascends directly toward the carotid canal and is crossed
laterally, in ascending order, by the hypoglossal nerve, occipital artery, posterior belly of
the digastric and associated stylohyoid muscle, and the posterior auricular artery. Still
higher and close to the base of the skull, the external carotid artery is anterolateral to the
internal carotid artery, and the stylopharyngeus muscle and associated glossopharyngeal
nerve, the pharyngeal branch of the vagus, and the stylohyoid ligament all pass laterally
to the internal carotid, between it and the external carotid artery.

FIGURE 1.19. Arterial supply of the neck. 1, Common
carotid artery; 2, superior laryngeal artery; 3, superior
thyroid artery; 4, internal carotid artery; 5, external
carotid artery; 6, lingual artery; 7, occipital artery; 8,
ascending pharyngeal artery; 9, inferior alveolar artery;
10, maxillary artery; 11, ascending palatine artery; 12,
facial artery; 13, mental artery; 14, submental artery; 15,
angular artery; 16, infraorbital artery; 17, buccal artery;
18, sphenopalatine artery; 19, middle meningeal artery; 20, superficial temporal artery.



After its origin in the carotid triangle, the external carotid artery passes upward, deep to
the posterior belly of the digastric and stylohyoid muscles, crosses the styloglossus and
the stylopharyngeus muscles on their lateral aspects, and parallel to the ramus of the
mandible passes into the deeper portion of the parotid gland. The external carotid artery
has branches to the superior thyroid, lingual, facial, ascending pharyngeal, occipital,
posterior auricular, maxillary, transverse facial, and superficial temporal arteries.
Venous Supply
The veins of the neck vary considerably in their connections with each other and in their
relative sizes (Fig. 1.20). Those conducting blood downward from the head and face
include the external jugular, anterior jugular, internal jugular, and vertebral veins. At the
base of the neck are the suprascapular and transverse cervical veins and the subclavian
vein, which unites with the internal jugular vein to form the brachycephalic or innominate
vein. The subcutaneous veins and the external and anterior jugular veins are especially
variable in size and course.

FIGURE 1.20. Venous supply of the neck. 1, Subclavian
vein; 2, internal jugular vein; 3, anterior external jugular
vein; 4, superior laryngeal vein; 5, superior thyroid vein;
6, common facial vein; 7, posterior external jugular vein;
8, retromandibular vein, anterior division; 9,
retromandibular vein, posterior division; 10, inferior
alveolar vein; 11, posterior auricular vein; 12, superficial
temporal vein; 13, deep temporal vein; 14, pterygoid
plexus; 15, deep facial vein; 16, infraorbital vein; 17, angular vein; 18, mental vein; 19,
facial vein; 20, external palatine vein.



Lymphatic Vessels
The lymphatic system of the neck consists of numerous lymph nodes intimately
connected with each other by lymphatic channels and the terminations of the thoracic and
right lymphatic ducts. The deep cervical lymph nodes are numerous and prominent, and
many of them are large. They form a chain embedded in the connective tissue of the
carotid sheath. Most are in that portion of the sheath around the internal jugular vein.
They extend from the base of the skull to the base of the neck. Two nodes that deserve
particular attention are the superior jugulodigastric node at the junction of the internal
jugular vein and the posterior belly of the digastric and the inferior juguloomohyoid node
at the junction of that muscle and the internal jugular vein. Block resection of the neck in
a standard radical or modified manner relies on reproducible and consistent lymphatic
drainage pathways for success.
Viscera
The visceral structures of the neck include the thyroid and parathyroid glands, a portion
of the pharynx, the larynx, the trachea, the esophagus, and sometimes portions of the
thymus (Fig. 1.21). The thyroid gland lies below and on the side of the thyroid cartilage
covered anteriorly by the infrahyoid muscles. A pyramidal lobe of the thyroid may extend
superiorly from the isthmus that connects the two lobes of the thyroid gland. On the
posterior surface of the thyroid gland lie the paired parathyroid glands. Successful
parathyroid exploration and thyroidectomy depend on accurate identification and
preservation of the recurrent laryngeal nerves and identification of the parathyroid glands.
Landmarks that are used successfully to locate these structures include the trachea,
common carotid artery, and inferior thyroid artery, which form a triangle within which
the surgeon usually finds the recurrent laryngeal nerve. Lymphatic drainage occurs along
the peritracheal nodes. Venous drainage similarly is directed inferiorly along the inferior
thyroid veins.

FIGURE 1.21. Thyroid and parathyroid glands.



The four or more parathyroid glands develop from the dorsal extremities of the third and
fourth pharyngeal pouches. As the thyroid and thymus and their associated parathyroid
glands move caudally from the region in which they originate, the thymus normally
descends beyond the level at which the thyroid halts. The parathyroids from the fourth
pouches (superior parathyroid glands) typically are situated more craniad than the thyroid
gland, and those derived from the third pouches (inferior parathyroid glands) are typically
freed from the thymus and become associated with the thyroid gland at its lower pole.
Both sets of parathyroid glands usually are situated on the posterior aspect of the lateral
lobes of the thyroid gland, but there are many exceptions. Because of the manner in
which they arise and migrate into the neck, the glands often are displaced and may be
situated in other portions of the thyroid gland or lie above or below it.
BIBLIOGRAPHY
Hollinshead WH. Anatomy for surgeons: the head and neck, 2nd ed. Hagerstown, MD: Harper & Row,
1968.
Netter FH. Atlas of human anatomy. Summit, NJ: Ciba-Geigy, 1989.
Pernkopf E. Atlas of topographical and applied human anatomy: head and neck. Philadelphia: WB
Saunders, 1963.
Williams PL, Warwick R, Dyson M, eds. Gray's anatomy, 37th ed. Edinburgh: Churchill Livingstone,
1989.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

2 GENETICS
Head & Neck SurgeryOtolaryngology
2




GENETICS
ADRIANE P. CONCUS
MICHAEL S. BENNINGER
DANIEL L. VAN DYKE
BRUCE R. KORF

A.P. Concus and M.S. Benninger: Department of OtolaryngologyHead and Neck Surgery, Henry Ford
Hospital, Detroit, Michigan.
D.L. Van Dyke: Department of Medical Genetics, Henry Ford Hospital, Detroit, Michigan.
B.R. Korf: Partners Center for Human Genetics, Harvard Medical School, Boston, Massachusetts.


DNA and Chromosomes
Patterns of Genetic Transmission
Autosomal Recessive Inheritance
Autosomal Dominant Inheritance
Sex-linked Inheritance
Multifactorial Inheritance
Chromosomal Anomalies
Nontraditional Patterns of Inheritance
Genetic Disease Mapping
Molecular Diagnosis of Human Genetic Disorders
Gene Therapy
Treatment of Patients with Genetic Disorders
Genetics of Otolaryngologic Disorders
Congenital Malformations
Hereditary Deafness
Genetics of Head and Neck Cancer
Conclusion
Chapter References
Understanding of human genetics is growing exponentially. Genes determine basic
human form and function, and it is becoming increasingly evident that genetic
abnormalities contribute at least in part to most disorders. Genetic information and
knowledge are leading to earlier disease identification and improved treatment
capabilities. Advances have allowed detection with a single blood test of diseases once
identified by painstaking evaluation of family trees and subsequent chromosome analysis.
Familiarity with and improved understanding of normal and abnormal human genetics
have become critical to the practice of medicine because genetics plays an ever-
increasing role in diagnosis, prevention, and management of disease. This chapter is an
overview of human genetics. Described are patterns of genetic transmission and the
molecular basis of genetic disorders. Principles of genetic counseling are presented.
Common genetic malformations in otolaryngology are discussed as are the genetics of
hereditary hearing loss and head and neck cancer.
DNA AND CHROMOSOMES
All genetic information is encoded by four bases composing molecules of
deoxyribonucleic acid (DNA) (Fig. 2.1). Sequences of DNA, called genes, are transcribed
into corresponding sequences of ribonucleic acid (RNA), which are translated into
sequences of amino acids that constitute specific proteins. The proteins serve as structural
components of cells and tissues or as enzymes that catalyze chemical reactions. The
entire developmental program of an organism is effected by the precisely timed and
orderly expression of genes. The human total DNA content, or genome, contains about 3
billion base pairs of DNA, which encode more than 80,000 functional RNA molecules
and proteins (1).

FIGURE 2.1. Flow of information from base sequence of
DNA through RNA to amino acid sequence of protein.
The four bases of DNA are adenine (A), guanine (G),
cytosine (C), and thymine (T). In the two complementary
strands of helical DNA, A is paired with G, and T is
paired with C. The information in one strand is copied
into a complementary strand of RNA, in which uracil (U)
is substituted for thymine. RNA is translated into an
amino acid sequence. Triplet codons in the RNA are underscored. The illustrated
sequence is a small portion of the gene for connexin 26, a gap junction protein, mutations
for which are responsible one type of autosomal recessive nonsyndromic hearing loss.



Most of the human genome is contained within the nucleus of the cell, packaged into
structures called chromosomes. Each somatic cell contains 46 chromosomes, the size and
structure of which are the same for every person (Fig. 2.2). The nonsex chromosomes
(autosomes) are represented in pairs, one inherited from each parent. The sex
chromosomes are two X chromosomes in women and girls or an X and a Y in men and
boys. Each chromosome consists of a single continuous DNA molecule. In addition to the
nuclear genome, each mitochondrion contains several copies of a circular DNA molecule
of approximately 16,500 base pairs. The mitochondrial DNA encodes some of the
proteins involved in oxidative phosphorylation, transfer RNA (tRNA), and ribosomal
RNA (rRNA). Mutations in mitochondrial DNA account for a set of diseases with a
distinctive pattern of maternal transmission.

FIGURE 2.2. Normal male karyotype. The chromosomes
were obtained from dividing peripheral blood
lymphocytes. They were stained for G banding, which is
responsible for the banding that enables unequivocal
identification of each chromosome.



A preliminary map of the human genome has been completed through the coordinated
efforts of the Human Genome Project. The ability to identify genes responsible for
specific human disorders and provide tools for diagnosis is of great clinical importance
(1). Ethical issues regarding discrimination, privacy, and ownership of genetic
information have been raised.
PATTERNS OF GENETIC TRANSMISSION
Genetic disorders occur sporadically, as is typical of chromosomal anomalies and
mutations that are genetically lethal, or they are transmitted from generation to
generation. The classic patterns of genetic transmission include autosomal recessive,
autosomal dominant, and X-linked.
Several terms are used to describe patterns of genetic transmission. The constitution of a
particular genetic locus is called the genotype of the cell or organism. The particular
forms of a gene on each chromosome are alleles. Persons who carry two identical alleles
at a gene locus are said to be homozygous. Those who carry two different alleles (e.g.,
one normal and one mutant) are heterozygous. The observable characteristics of a cell or
organism that are controlled by a particular genetic locus are called the phenotype.
Autosomal Recessive Inheritance
A prototypic pedigree for a family with an autosomal recessive disorder is illustrated in
Fig. 2.3A. Autosomal recessive traits are expressed only if both copies of a gene are
affected by mutation, that is, they are homozygous. Both parents usually are
heterozygous, each having one normal copy of the gene and one mutant copy. Because
each carrier parent has a chance of one in two (50%) of passing the mutant gene to any
child, the risk of a child's receiving the mutant gene from both parents and having the
recessive trait is one in four (25%). Siblings of affected persons have a 67% risk of being
carriers, but their risk of having affected offspring themselves generally depends on the
frequency of the mutant gene in the population. Heterozygotes usually display no
phenotypic effects of carrying the mutant allele. Autosomal recessive traits that are lethal
before childbearing age, such as Tay-Sachs disease, generally occur within sets of
siblings, and there is no evidence of the disorder in previous generations. Such traits also
tend to occur more commonly in families in which the parents are consanguineous.

FIGURE 2.3. Pedigrees show recessive (A), dominant
(B), and X-linked inheritance (C). Male family members
are indicated by squares and female members by circles.
Filled-in symbols are persons with the trait. Half-filled
symbols in the autosomal recessive pedigree are carriers.
Female family members with dots in the center of the
circle on the X-linked pedigree are carriers.



Many autosomal recessive disorders are more frequent in specific racial or ethnic
populations. This frequency represents the expression of a mutation present in one or a
few of the founding members of a group (founder effect) and a tendency for marriages to
occur within the same group. Autosomal recessive deafness, which is entirely consistent
with a normal life span and normal reproduction, can be present in two generations if
both deaf parents are homozygous for the same recessive form of deafness. Such
marriages would cause deafness among all the children. It is more typical, however, for
all children of such couples to have normal hearing, because there are many genetic
causes of deafness, and most such couples have different genetic forms of deafness.
Hurler syndrome, or mucopolysaccharidosis (MPS) type I, is an example of an autosomal
recessive trait for which the gene is well understood (2). Hurler syndrome is caused by a
mutation in the -L-iduronidase gene (IDUA) that causes production of a protein with
absence of normal enzymatic activity. Heterozygotes retain sufficient enzyme activity to
be healthy, but homozygotes cannot metabolize mucopolysaccharides, and these
compounds are stored in many tissues. The Hurler phenotype is a progressive disease that
includes corneal opacity, hearing loss, enlarged tongue, hepatosplenomegaly, joint
contractures, and life-threatening respiratory, cardiac, and gastrointestinal complications.
A different mutation in the same gene is the cause of Scheie syndrome, a less severe form
of MPS (type V) without mental retardation, corneal opacity, or stiff joints. Because the
enzymatic activity of the protein is low but not absent, the metabolic block is incomplete.
Persons who are compound heterozygotes, with one MPSI allele and one MPSV allele,
have an intermediate phenotype, called Hurler-Scheie syndrome. There are many
different mutations within the DNA sequence of the gene. Each is associated with a
specific reduced activity of the enzyme. Today it is understood that most affected persons
who are not the product of consanguineous matings are compound heterozygotes for two
different mutations of the IDUA gene and that the phenotype (Hurler, Scheie, or Hurler-
Scheie) depends on the combined enzymatic activity of the enzyme products of the two
IDUA alleles.
Autosomal Dominant Inheritance
Unlike autosomal recessive inheritance, autosomal dominant traits are expressed in
heterozygotes, who have a 50% chance of passing the mutant gene from generation to
generation (Fig. 2.3B). For this reason, such traits are expressed by members of each
successive generation. Both sexes can be affected, and men and women have an equal
chance of transmitting the gene to the next generation. Both parents of a child with an
autosomal dominant disorder should be examined for signs of the condition. If neither is
affected, the recurrence risk depends on the rate of penetrance of the disorder. In a
disorder with complete penetrance, a child may be affected sporadically because of new
mutation, which conveys a low risk of recurrence for the parents.
Classic autosomal dominant traits, such as neurofibromatosis type 1 (NF1), may exist in a
family for many generations. In some instances, the person affected by the autosomal
dominant trait appears to be the only affected member of the family. One explanation is
nonpenetrance, which is the apparent lack of phenotypic effect of a gene in a known
carrier. NF1 is typical of many autosomal dominant traits in that its expression varies
among individuals. About 60% of persons older than 20 years who carry the NF1 gene
have cutaneous neurofibromas, 17% have scoliosis, 13% have optic glioma, and 97%
express five or more cafe-au-lait spots by 20 years of age. Many other features are
associated with this syndrome. Therefore the penetrance of the gene approaches 100% if
the entire spectrum of the phenotype is considered. Nevertheless, about 50% of patients
with NF1 appear to have no family history of the disease and probably do have new
mutations. This apparently high rate of mutation in the NF1 gene may be accounted for
partly because the gene is large and perhaps because segments of the gene sequence are
predisposed to mutation, especially during spermatogenesis.
Sex-linked Inheritance
Traits expressed by genes on the X or Y chromosome are called sex-linked. Most sex-
linked disorders among humans involve genes on the X chromosome. Because a father
transmits a Y chromosome to his son, X-linked traits are not passed among male family
members. A woman who carries an X-linked recessive disorder has a 50% chance of
transmitting the condition to each son and a 50% risk of transmitting carrier status to each
daughter (Fig. 2.3C). Rare X-linked recessive disorders, such as Duchenne muscular
dystrophy, occur mostly among male carriers, who express only the mutant gene because
they have only one X chromosome. Female carriers are heterozygous and usually do not
manifest the disorder.
X-linked Kallmann syndrome is caused by a mutation that results in a deficiency of
hypothalamic gonadotropin-releasing hormone. The responsible gene, KAL, was
localized to the distal short arm of the X chromosome (band Xp22.3). The protein
product of the gene appears to act during embryogenesis as a cell adhesion molecule
responsible for normal neuronal cell migration (3). Boys with Kallmann syndrome have
hypogonadotropic hypogonadism, micropenis, cryptorchidism, unilateral renal agenesis,
and other defects. They also have complete, or nearly complete, anosmia due to agenesis
of the olfactory lobes, so a simple test for this disorder is the University of Pennsylvania
Smell Identification Test balanced with ammonia testing, which is sensed through cranial
nerve V, not cranial nerve I. Effective hormonal therapy for hypogonadism and infertility
is available. There also are autosomal dominant and autosomal recessive forms of
Kallmann syndrome with variable expression of the anosmia, and there is variable
expression of the phenotype among women and girls. X-linked dominant traits can be
expressed by both sexes. In some cases, the effects among boys are so severe as to be
incompatible with survival.
Multifactorial Inheritance
Many traits appear to cluster in families but do not display the transmission expected for
a single-gene dominant or recessive trait. An example is cleft lip, which is a relatively
rare, sporadic trait. Although recurrence in families occurs far less often than would be
expected by the rules of mendelian inheritance, the risk of recurrence in a family with one
affected child is greater than the population risk. Monozygous (identical) twins are more
frequently concordant for the trait than dizygous (fraternal) twins, suggesting that
inheritance plays some role in the disorder. Such traits are said to be subject to
multifactorial inheritance, meaning that many factors, including several distinct genes
and environmental factors, contribute to the trait. Quantitative attributes, such as height,
are believed to be controlled by multifactorial inheritance. Congenital malformations,
such as cleft lip and neural tube defects, are explained by the threshold model of
multifactorial inheritance, in which a combination of genetic and nongenetic factors add
to create a liability for the malformation (Fig. 2.4). The malformation occurs only if the
liability exceeds a threshold value. The theory of multifactorial inheritance explains many
sporadic congenital malformations. Families in which a known multifactorial disorder
has occurred usually are counseled with empiric recurrence risk data.

FIGURE 2.4. The threshold model of multifactorial
inheritance. There is a distribution of liability for the trait
in the population, shown here as a normal distribution.
All persons to the left of the threshold liability do not
express the trait, and those to the right are affected.



Chromosomal Anomalies
The disorders discussed earlier are caused by mutations of single genes. Other disorders
simultaneously involve several genes. The most extreme examples are disorders in which
there are extra copies of an entire chromosome. The best known is Down syndrome,
produced by an extra copy of chromosome 21. Other chromosomal abnormalities
compatible with live birth include trisomy of chromosomes 13, 18, X, and Y (4).
Chromosome loss is less well tolerated and usually causes death in utero. The apparent
exception is the 45,X karyotype (Turner syndrome), but even here, most 45,X
conceptions do not survive to term. The population incidence of Turner syndrome is
approximately 1/3,000, and many of these individuals are mosaic, having a 46,XX or
other cell population in addition to the 45,X cell population. Most abnormalities of
chromosome number occur sporadically as a result of errors of chromosome segregation
during meiosis.
Another mechanism of chromosomal anomaly is rearrangement, which includes deletion,
duplication, translocation, or inversion. Deletions and duplications tend to have
widespread phenotypic effects, including mental retardation, growth retardation, and
multiple unrelated congenital malformations. The phenotypic effect depends on the
specific genetic material gained or lost and the extent of gain or loss. In general, a gain of
1% or a loss of 0.5% of the genome is consistent with viability and can occur in a
balanced configuration, in which there is no net loss or gain of material. Persons with
balanced translocations or inversions usually are phenotypically normal but have a risk of
transmitting an unbalanced chromosomal constitution to offspring. The result is familial
transmission of a disorder of multiple congenital anomalies.
A microdeletion syndrome is caused by duplication or deletion of a small segment of
chromosome material that contains a small number of few genes, which are functionally
unrelated but by chance are linked together on the chromosome. The phenotype may vary
because of different breakpoints, making delineation of a clear syndrome difficult (5).
Affected persons usually appear sporadically, but familial clusters are known and
typically are caused by a balanced chromosome rearrangement that runs in the family.
Before the chromosomal basis was understood, such conditions were thought to represent
autosomal recessive or new dominant mutations (6).
An example of a microdeletion syndrome of interest to otolaryngologists is
velocardiofacial syndrome. This is a heterogeneous disorder usually caused by a
microdeletion in chromosome 22, band 22q11.2 (Fig. 2.5) (7). Other dysmorphology
syndromes known to be associated with the same microdeletion include DiGeorge and, at
least occasionally, CHARGE (coloboma of the iris, heart disease, atresia of the choanae,
retarded growth and development, genital and ear anomalies) and 3C
(craniocerebellocardiac), Bernard-Soulier, Opitz G and BBB, and Cayler cardiofacial
syndromes. The phenotype is variable, but the diagnosis usually is made when the
constellation of a conotruncal heart defect and other malformations, such as
hypocalcemic seizures and hypoplasia of the thymus and parathyroid glands of DiGeorge
syndrome, is present. Hearing loss is a frequent associated finding. The deletion
sometimes is familial, appearing in pedigree analysis as an autosomal dominant disorder
with variable expression. The proband typically is the more severely affected person, and
some family members have only one feature of the phenotype, such as ventricular
outflow or aortic arch malformation. It has been estimated that 15% to 20% of such cases
are associated with this microdeletion of chromosome 22 (7).

FIGURE 2.5. Chromosomal microdeletions and
fluorescein in situ hybridization (FISH) image of
velocardiofacial syndrome. The chromosome pairs are G-
banded, and the pattern of bands matches the pattern
drawn on the adjacent ideograms. Brackets mark the
region of interest, and the deletion chromosome is on the
right of each chromosome pair. In FISH fluorescent-
tagged DNA sequences (probes) are used that hybridize
to the segment of interest. Absence of the fluorescent signal from the probe indicates a
deletion. One of the chromosomes is labeled normally, with the syndrome-specific probe
(large arrow) and a control probe (small arrow). The microdeletion chromosome
expresses only the marker probe signal. FISH has become a useful method when a
specific microdeletion syndrome is suspected.



The velocardiofacial syndrome deletion usually is not detected with classic chromosome
analysis methods. For this reason, it is important to involve a dysmorphologist familiar
with such conditions and who can request the specific cytogenetic test to establish the
diagnosis.
NONTRADITIONAL PATTERNS OF INHERITANCE
Several nontraditional patterns of genetic transmission have been recognized in recent
years. One is maternal inheritance due to transmission of genes in mitochondrial DNA.
The entire mitochondrial DNA complement of a child is inherited from the mother.
Mutations in mitochondrial genes therefore are transmitted from a mother to all her
children. Because mitochondria are excluded from sperm, the father does not pass a
mitochondrial mutation to any child. Characterized mitochondrial disorders include Leber
hereditary optic atrophy and encephalomyopathy (8) and at least two genetic forms of
isolated deafness (9).
Another nontraditional inheritance pattern is dynamic mutation, or unstable trinucleotide
repeats, which is responsible for several forms of neurodegenerative ataxia and a few
other disorders (Table 2.1) (10). Some segments of DNA normally comprise 20 or more
repetitions of a three-base sequence, such as CAG or CGG. Some persons have more
copies, which can cause instability during gametogenesis and production of offspring
who carry very long repeats. In some conditions, the number of repeats in an affected
person is about double the normal number, and in other conditions, the number of repeats
exceeds 1,000. Although the inheritance pattern of these conditions behaves in many
respects as a simple mendelian trait, mostly autosomal dominant, several features set
them apart. Expansion of the DNA repeat usually is more likely in either spermatogenesis
or oogenesis, leading to differences in phenotype, depending on which parent carries the
mutation. The severe congenital form of myotonic dystrophy occurs only among
offspring of affected mothers because expansion occurs preferentially during oogenesis.
In fragile X syndrome, expansion likewise is limited to oogenesis, so daughters of
unaffected men who transmit fragile X syndrome never are affected, whereas some sons
and daughters of carrier women are affected. In Huntington disease, large expansions are
transmitted preferentially by the man during spermatogenesis. The exact mechanism for
this parent-of-origin effect in dynamic mutations is not well understood but has been
postulated to reflect selection against expanded repeats during gametogenesis (11). Once
a DNA repeat begins to expand in length, expansion can continue with each succeeding
generation. This dynamism of the trinucleotide repeat sequence explains a phenomenon
known as genetic anticipation, whereby the age at onset of the disorder is younger with
each succeeding generation and is accompanied by a more severe phenotype.

TABLE 2.1. INHERITED DISORDERS CAUSED BY
TRINUCLEOTIDE REPEAT EXPANSION
(DYNAMIC MUTATIONS)



A third type of genetic disorder is associated with the phenomenon of genetic imprinting
(12). For most genes, both copies are genetically active. For other genes, however, only
the maternally or the paternally inherited copy is genetically active. Each of these genes
is imprinted during either paternal or maternal gametogenesis. Maternal and paternal
imprints can be recognized from their DNA methylation patterns, usually involving a
cytosine-guanine (CpG) DNA base sequence. Once it is set, the methylation imprint can
be faithfully maintained during mitosis by means of postreplication methylation. The
imprint is erased only when someone of the opposite sex transmits the gene.
The classic examples of syndromes that exhibit imprinting are Prader-Willi and
Angelman syndromes. Both Prader-Willi syndrome and Angelman syndrome usually are
associated with microdeletions of the region 15q11 to 15q13. Specific segments within
this region are responsible for each syndrome, but an imprinting defect is demonstrated
by the fact that a deletion of paternal origin causes Prader-Willi syndrome, whereas an
otherwise identical deletion of maternal origin causes Angelman syndrome. Studies of
DNA methylation patterns show that some genes in region 15q11-q13 are imprinted
during oogenesis and that other genes are imprinted during spermatogenesis. A person
must have one paternally and one maternally inherited chromosome 15 to ensure normal
expression of all genes in this chromosome region. A microdeletion of paternal
chromosome 15 causes Prader-Willi syndrome, and microdeletion of maternal
chromosome 15 causes Angelman syndrome. Some patients with Prader-Willi syndrome
and Angelman syndrome do not have a microdeletion. Some of these persons
demonstrate uniparental disomy, whereby both chromosome 15s are inherited from the
same parent. This has the same effect as deletion of one of the genetic imprints. Errors in
the imprinting process also can cause lack of normal gene expression. In rare instances,
persons with familial Angelman syndrome have normal methylation patterns. These
patterns probably involve a point mutation in the imprinting control region of the gene or
genes responsible for the Angelman syndrome phenotype, and the inheritance pattern is
autosomal recessive (13).
GENETIC DISEASE MAPPING
The profound effect of molecular genetics on clinical practice is the result of the ability to
identify genes responsible for specific disorders among humans and to provide tools for
diagnosis. Completion of a first draft of the human genome sequence is vital to
accelerating the process of gene identification. The basic technology is gene cloning (Fig.
2.6). Segments of human DNA, which may represent random fragments of the genome or
may correspond to specific expressed genes, can be inserted (cloned) into bacterial, viral,
or yeast DNA and grown in culture. A single bacterial or yeast colony that has
incorporated a piece of human DNA of interest can be isolated. Gene libraries that
incorporate fragments of the human genome or that incorporate DNA copies of
messenger RNA (cDNA) can be made. The cDNA libraries represent only these genes
expressed in a particular cell type and are useful for cloning functional genes.

FIGURE 2.6. Process of cloning of genomic DNA. DNA
is cleaved with a restriction enzyme into a population of
fragments. Bacterial plasmid DNA is cleaved with the
same enzyme, and the fragments are randomly ligated
into the plasmid DNA circles. The recombinant plasmids
are then introduced into bacteria, which are grown into
colonies. Each colony on an agar plate is derived from a
single bacterium that incorporated a single recombinant
plasmid. The bacterial colonies are screened for those with DNA of interest, which can be
isolated, grown in quantity, and used to prepare purified cloned DNA.



Identification of genes involved in clinical disorders has proceeded in several phases. The
first genes to be cloned were those for which the protein product was already known,
including globin genes (e.g., sickle cell disease, thalassemia) and enzymes (e.g.,
phenylketonuria or Hurler syndrome). As genomic tools became further refined, a second
approach, positional cloning, became possible. This began with mapping the disease
gene, usually by means of tracking the segregation of the disease gene through a family
in relation to genetic markers that had already been mapped (linkage analysis). DNA was
isolated in this region and examined for mutations among affected persons. This
approach has seen major success in identification of genes for conditions such as
Duchenne muscular dystrophy, cystic fibrosis, NF1, and NF2.
With the gene sequence available, a candidate gene approach is increasingly used. The
location of the disease gene is determined, usually by means of linkage analysis. Then
genes known to reside in the region are examined for mutation. The procedure starts with
the most plausible candidates based on patterns of expression or the physiologic roles of
the gene products.
Identification of a gene responsible for a clinical disorder is a scientific advance.
Diagnostic tools can be developed, and gene therapy becomes possible in some cases.
Most important, the physiologic basis of the disorder becomes amenable to study, and the
way is opened to develop pharmacologic approaches to treatment.
MOLECULAR DIAGNOSIS OF HUMAN GENETIC DISORDERS
In keeping with the interesting variety of gene expression, a diversity of mutations, such
as base substitutions, insertions, deletions, and chromosomal rearrangements, can
produce genetic disorders among humans. A single disorder typically is caused by many
different kinds of mutations of the same gene in different persons (Fig. 2.7). A mutation
classically is thought to involve the coding region of a gene in which mutations of one or
a few nucleotides produce an abnormal protein or loss of the protein. Mutations in the
noncoding regions of the gene, such as the promoter region, splice sites, and termination
and polyadenylation signals, also can produce abnormal proteins or reduced levels of
normal proteins. Structural rearrangements (insertions or deletions) involving several
nucleotides to thousands of nucleotides can produce aberrant proteins or result in absence
of proteins (14).

FIGURE 2.7. Diagram shows prototypic gene and the
consequences of mutations at different sites. Genes are
transcribed from 5' to 3'.



Because the causes of many genetic disorders have been elucidated and the genetic map
is more complete, it has become increasingly possible to use molecular genetic
approaches for diagnosis. Such approaches allow precise definition of whether a person
has inherited a mutant gene, often before appearance of the disease phenotype, and can
provide the basis of prenatal diagnosis. Two approaches are useddirect detection and
indirect detection (linkage analysis) of abnormal genes.
Direct detection of a mutation is possible if the responsible gene is cloned and a limited
number of mutations are known to cause the disease. Most molecular diagnostic tests rely
on amplification of a target sequence with a polymerase chain reaction (PCR) (Fig. 2.8).
Short sequences of single-stranded DNA (15 to 30 bases called oligonucleotides)
homologous to sequences on the opposite strands of genomic DNA serve as the flanking
regions for amplification of a DNA fragment of interest. The genomic DNA is denatured
into single strands by means of heating, and the synthetic oligonucleotides are allowed to
anneal and serve as starting points for a DNA synthesis reaction. This process is repeated
sequentially. The result is exponential synthesis of new DNA that corresponds to the
region bounded by the two oligonucleotides. PCR technology has revolutionized study of
the human genome, including typing of genetic markers, mutation screening, detection of
point mutations, cDNA and genomic DNA cloning, genome walking, DNA sequencing,
and in vitro mutagenesis (14). A variety of strategies are used to identify mutations. They
range from complete gene sequencing to approaches that target a specific single-base
change (Table 2.2). Laboratories that offer clinical or research-based molecular diagnosis
for specific disorders are listed at the Gene Tests website (http://www.genetests.org/).

FIGURE 2.8. Polymerase chain reaction. Synthetic
oligonucleotide primers (thick lines) bind to the two
opposite strands of heat-denatured DNA and prime a
DNA synthesis reaction in opposite directions. The
process is repeated several times to produce an
exponential increase in the DNA between the two
primers. The products can be analyzed for mutations.



TABLE 2.2. PARTIAL LIST OF METHODS USED
IN DIRECT MOLECULAR ANALYSIS



If the disease gene is not cloned but linkage has been established between the disease
locus and marker genes, or if the gene has too many defects, making direct analysis
impractical, linkage studies can be used for diagnosis in some families. Minor variations
of base sequence, polymorphisms, are common among humans. Most of these variants
are not located in coding regions of genes and therefore are not responsible for
phenotypic effects; however, they can be detected by means of PCR or Southern blotting
and constitute heritable markers that can be tracked with a disease trait within a family.
The DNA markers do not correspond to molecular defects within a gene but merely tag a
disease-bearing chromosome as it is inherited. The use of linkage analysis in the
diagnosis of a genetic disorder is illustrated in Fig. 2.9. Although it is a powerful
approach, genetic linkage is subject to diagnostic error and is not possible for all families.
Diagnostic error is caused by genetic recombination during meiosis, which can change
the association of a particular marker allele with a disease allele, by misattributed
paternity, or by genetic heterogeneity (diseases that look phenotypically identical but are
caused by defects in different genes, such as Alzheimer disease). The technique can be
used only by families in which there is a clear pattern of mendelian transmission, for
which the clinical diagnosis implicates the linked disease gene unequivocally, and in
which the persons who carry the disease gene are heterozygous for the marker, allowing
the two chromosomes to be differentiated.

FIGURE 2.9. Linkage analysis for diagnosis in a family
with an autosomal dominant disorder. The grandfather is
affected with an autosomal dominant trait and is
heterozygous for the normal gene (+) and the disease
gene (D). A nearby marker locus is indicated as being
closely linked. The grandfather has the A allele, and his
wife, who does not have the disease, has the B allele. The
affected female member of the second generation must
have the A allele on the same chromosome as the disease allele, having received both
from her father. She passes the A allele to a son, who is affected, and the B allele to a
daughter, who is unaffected. In this family, the marker gene allows the mutant gene to be
followed through the family.



GENE THERAPY
Knowledge of the structure of a gene responsible for a genetic disorder can lead to
improved therapy through earlier diagnosis. In addition, the disorder can be managed
prospectively with classic treatments or new knowledge of pathogenesis gained from
study of the gene product. The long-term hope for genetic therapy is to replace a
defective copy of a gene in the cell and reverse the effects of the mutation. There are a
number of ways of introducing foreign genes into cells and obtaining stable expression of
these inserted sequences. Human gene therapy is being attempted in experimental settings
for diseases such as cystic fibrosis, Duchenne muscular dystrophy, familial
hypercholesterolemia, and cancer. There are many biologic obstacles to overcome,
including obtaining sustained levels of expression comparable to those of normal cells,
and targeting the inserted genes to the appropriate cell type. Currently more than 200
gene therapy protocols have been approved for treatment of patients with cancer,
acquired immunodeficiency syndrome, and genetic diseases (15).
There are four general strategies in gene targeting. In one method used when there is a
loss of normal gene function, extra copies of the normal gene are introduced into cells.
This method can be effective in the management of autosomal recessive disorders, such
as cystic fibrosis. In one study, investigators used adenovirus vector to introduce wild
type p53 tumor suppressor gene into malignant tumors of the head and neck. A favorable
response occurred with regression or stabilization of disease for 3.5 months among one
half of the patients tested (16).
Targeted killing of specific cells is a second approach often used in gene therapy for
cancer. In this approach, the inserted gene produces a lethal toxin that kills the target
cells, encodes a gene that is sensitive to a certain administered drug, or stimulates the
immune system to kill the target cells. Studies are under way in which a plasmid vector is
used to introduce major histocompatibility complex HLA-B7 into squamous cell
carcinoma of the head and neck and thereby induce immunologic killing of the cancer.
Preliminary studies show a 20% to 25% response rate (15).
A third approach to gene therapy is to correct the mutation either at the DNA level
(homologous recombination) or at the RNA level (ribozymes). The final approach is
targeted inhibition of gene expression at the DNA, RNA, or protein level, such as use of
antisense genes. This fourth approach may be yield important techniques for managing
many types of cancer and infectious diseases (14).
TREATMENT OF PATIENTS WITH GENETIC DISORDERS
The American Society of Human Genetics has defined genetic counseling as a
communication process which deals with . . . the occurrence or risk of occurrence of a
genetic disorder in a family (17). The process includes helping the family to (a)
understand the medical facts, including the diagnosis and course of the disorder, (b)
appreciate the role of heredity in the disorder, including knowledge of the risk of
recurrence, (c) understand the options available to deal with the risk of recurrence, (d)
choose a course of action, and (e) make the best possible adjustment to dealing with the
disorder and the choices they make.
Correct diagnosis is key to caring for patients with inherited disorders. Many disorders
can appear similar clinically and yet be distinct genetically. Moreover, many genetic
disorders have pleiotropic effects. A pedigree should be constructed for the family,
similar to that shown in Fig. 2.3 to help recognize the pattern of transmission or
determine that a disorder is sporadic.
A difficult challenge in genetic counseling is posed if a child has a problem for which a
specific diagnosis cannot be made. Most often, this occurs when a child has congenital
malformations that do not fit a particular syndrome. It is always wise to examine these
children for chromosomal anomalies. At most institutions, an experienced
dysmorphologist or medical geneticist is available for consultation. If the chromosomes
are normal, it may be impossible to establish a specific cause. In this case, counseling
must take into account the possibility that the disorder has a genetic basis and that
recurrence is possible. Although the recurrence risk cannot be quantified in this situation,
empiric recurrence risk may be available. The family needs to understand that the lack of
a specific diagnosis or family history of the disorder does not preclude that the problem is
genetic and that recurrence is possible.
There are several options for dealing with risk of recurrence. Options likely to be
agreeable to a family depend on factors such as their perception of the severity of the
disorder, whether the disorder can be managed or be diagnosed prenatally, and the ethical
and religious beliefs of the family. Prenatal diagnosis, usually by means of amniocentesis
or chorionic villus sampling, is widely accepted and is available for cytogenetic disorders
and for an ever-increasing number of mendelian and nontraditionally inherited
conditions. Modalities for prenatal diagnosis includes level III ultrasound examination,
which can be used to detect some of the congenital malformations associated with many
syndromes.
Prenatal diagnosis is undertaken for several reasons. The most obvious is consideration of
pregnancy termination if a fetal anomaly is found. Other couples choose prenatal
diagnosis to allow planning for the medical needs if a child has an inherited disorder.
Prenatal surgical procedures can be performed for some anatomic defects. A major canon
of genetic counseling is to be nondirective. The counselor must present options in a
neutral manner, not allowing his or her opinions to influence a couple's decision. Having
a child with an inherited disorder imposes many practical and emotional stresses on a
family. Complex medical decisions may have to be made and a substantial financial
burden sustained. The disorder may be life threatening or may lead to chronic illness and
developmental impairment. On the other hand, a familial condition to which adaptation is
readily achieved, such as deafness, may not be considered a burden by the family. The
correct diagnosis may be of interest only in terms of the likelihood of having children
who share the trait of deafness and in terms of monitoring for associated problems such
as nephritis.
The medical issues can dominate all other issues for a family. Health professionals can
ease the burden by providing competent care, providing information in an understandable
manner, and maintaining open communication with the family and the other health care
professionals. The geneticist can play a special role by addressing the question of cause.
It is especially important to take a thorough family and pregnancy history. It is rare to
identify a specific environmental exposure that caused a child's problems, but it is routine
to learn that a family member is worried that an insignificant event might have
contributed. These concerns usually are disclosed only after directed questioning. After
recognizing the source of anxiety, the counselor or physician can reassure a family and
help them deal more directly with the medical and emotional issues at hand.
GENETICS OF OTOLARYNGOLOGIC DISORDERS
A large number of otolaryngologic disorders are known to be familial or to have a genetic
component. Although the details of these disorders are discussed elsewhere, some of the
more important are described herein to highlight the genetic issues raised.
Congenital Malformations
A variety of congenital malformations affect the ear, nose, and throat. Some occur as a
component of multiple congenital malformation syndromes, which may be caused by
single-gene mutations or chromosomal abnormalities. Others occur sporadically,
displaying multifactorial inheritance. A classic example is cleft lip, which occurs in
isolation or with cleft palate. Although facial clefts usually occur sporadically, they can
be a component of mendelian disorders or occur in association with multiple congenital
anomalies. This is also true of anomalies such as preauricular pits or malformation of the
external ear.
Kartagener Syndrome
Kartagener syndrome is an autosomal recessively inherited condition of dextrocardia,
situs inversus, immotile sperm, anosmia, bronchiectasis, and chronic cough, all secondary
to absence or malformation of the dynein arm structures of cilia.
Down Syndrome
Down syndrome, or trisomy 21, is the most common malformation syndrome and occurs
in increasing frequency with increasing maternal age. Common otolaryngologic
manifestations include upslanting palpebral fissure, low nasal bridge, macroglossia,
narrow palate, protruding tongue, and atlantoaxial instability.
Craniosynostosis
Apert syndrome involves craniosynostosis, syndactyly and midfacial malformations, and
mental retardation. Most cases are sporadic mutations. Crouzon syndrome involves
craniosynostosis, maxillary hypoplasia, and proptosis. Intelligence is normal. These
syndromes are transmitted in an autosomal dominant pattern.
Treacher Collins Syndrome
Treacher Collins syndrome or mandibulofacial dysostosis is characterized by a
hypoplastic mandible and maxilla, hypoplastic supraorbital rims, narrow face, depressed
cheek bones, bizarre inferiorly placed pinnae, downslanting palpebral fissures, and
normal intelligence. The inheritance pattern is autosomal dominant.
Hereditary Deafness
Both congenital and acquired forms of deafness can have a genetic basis (9). One in
every 1,000 infants is born with hearing loss. By the age of 80 years, more than 50% of
persons have some degree of hearing loss (18). As environmental and infectious causes of
hearing loss are being controlled, it is estimated that more than 60% of congenital hearing
impairment is genetic and that one third to one half of all deafness has an inherited
component (18). Hereditary hearing impairment (HHI) can be classified as syndromic or
nonsyndromic (9,18). Syndromic hearing loss (30% of all HHI) occurs in association
with other anomalous phenotypic features. Craniofacial malformations, renal
abnormalities, skeletal dysplasia, and pigmentary anomalies are some common examples.
Nonsyndromic hearing loss (70% of all HHI) occurs as an isolated deficit. Since
approximately 1990, positional cloning techniques have allowed rapid identification of a
number of single genes that cause nonsyndromic hearing loss.
Syndromic Hearing Loss
Hundreds of autosomal dominant, recessive, and X-linked forms of syndromic hearing
loss have been described. Molecular genetic studies have revealed the locations of genes
responsible for some of these syndromes. Waardenburg syndrome is a dominantly
transmitted disorder that includes sensorineural hearing loss, dystopia canthorum (widely
spaced inner canthi), and a disorder of neural crest migration. Intrafamilial heterogeneity
in the phenotype (called variable expressivity) exists. PAX3, a gene on the long arm of
chromosome 2, has been found to be mutated in many persons with Waardenburg
syndrome (19). About 83% of persons who carry the gene have penetrance, that is they
have physical manifestations. Dystopia canthorum, heterochromia, or white forelock
occurs among approximately one third of gene carriers and deafness among
approximately 25% (20).
Another genetically heterogeneous disorder associated with hearing loss is Usher
syndrome. In Usher syndrome type I (USH1), partial sensorineural hearing loss occurs
with development of retinitis pigmentosa after the first decade of life (21). Families with
Usher syndrome type II (USH2) have congenital deafness and early onset of retinitis
pigmentosa. Five distinct Usher syndrome genes have been mapped to chromosome
bands 1q32 (USH2), 14q32 (USH1), 3q21 (USH3, the Finland variety), 11p15 (USH1C,
the Acadian variety), and 11q13 (USH1B) (22).
Pendred syndrome is an autosomal recessive disorder associated with goiter and an
increased risk of thyroid carcinoma. It has been mapped to the long arm of chromosome
7. There is variability in expression of the gene defect within families. Some members
have near-normal hearing, and some have unilateral deafness. Another mutation in the
gene responsible for Pendred syndrome may be responsible for one form of autosomal
recessively inherited nonsyndromic deafness (23).
Deafness and nephritis occur together in many conditions. Alport syndrome, for example,
is characterized by nephritis, deafness, and cataracts and can be inherited in an X-linked
or an autosomal pattern. Mutations in various collagen protein genes are responsible for
most forms of Alport syndrome, including the -5-collagen gene, which is located in the
short arm of the X chromosome (24), and genes that code for collagen IV subunits, which
have been mapped to chromosome 2 (25).
Nonsyndromic Hearing Loss
Since approximately 1995, linkage analysis has accelerated mapping of genes that cause
monogenic nonsyndromic hearing loss. Monogenic prelingual hearing loss is
approximately 75% autosomal recessive, 20% autosomal dominant, 5% X-linked, and
less than 1% mitochondrial (9). Two parents with autosomal recessive deafness can have
children with normal hearing because the mutant gene may be different in each parent.
By 1999, 44 gene loci on 19 chromosomes and 15 genes, including two mitochondrial
genes, for nonsyndromic hearing loss had been identified (Table 2.3) (9). These loci are
labeled DFN (for deafness). DFNA designates autosomal dominant loci; DFNB
designates autosomal recessive loci; DFN are the X-linked recessive loci (9). Protein
products of these deafness genes include transcription factors, myosin, connexin
(involved in formation of cell membrane channels), formin (involved in maintenance of
the inner ear cytoskeleton), ion transporters, structural proteins of the organ of Corti, and
extracellular matrix proteins. Mitochondrial genes responsible for monogenic
nonsyndromic hearing loss include the gene for 12S rRNA and the serine tRNA (9,18).

TABLE 2.3. NUCLEAR GENE LOCI FOR
NONSYNDROMIC HEARING LOSS



DFNB1 mutation (connexin-26) on chromosome 13q12 was the first cloned gene to be
implicated in and is the most common cause of nonsyndromic hearing loss. It accounts
for approximately one half of all cases of autosomal recessive prelingual hearing loss and
20% of all prelingual deafness (9). The hearing loss is moderate to profound but stable.
Connexin encodes cell plasma membrane channels involved in intercellular exchange of
ions and small molecules. Approximately 1% to 3% of white persons carry a DFNB1
mutation. Molecular screening is possible for connexin 26 abnormalities as part of the
diagnosis of hereditary prelingual deafness (9,18).
DFNA9 (the COCH gene) on chromosome 14q11-13 is the gene most frequently
involved in autosomal dominant postlingual hearing loss. Clinical features include
progressive hearing loss starting in the high frequencies and variable vestibular
symptoms. COCH is believed to encode an extracellular matrix protein. Deposits of
mucopolysaccharides have been found in the inner ears of patients with the DFNA9
mutations.
DFN3 (encoding the POU3F4 gene), located on chromosome Xq21, is the most common
X-linked locus involved in nonsyndromic hearing loss. Hearing loss is progressive with
fixation of the stapes footplate. POU genes encode transcription factors. POU3F4 is
expressed in the mesenchyme of the inner and middle ear, where it is involved in
maturation of bone (9).
The most frequent form of mitochondrial hearing loss involves mutation of the 12S
rRNA gene. This mutation occurs in association with aminoglycoside ototoxicity. The
mutated rRNA is likely more similar to bacterial rRNA, the target of aminoglycoside
antibiotics. Progress in identifying nonsyndromic HHI genes will clarify the underlying
molecular mechanisms of hearing and hearing loss, improve genetic counseling, and lead
to development of specific therapies for hearing loss.
Genetics of Head and Neck Cancer
Cancer of the head and neck accounts for about 5% of all deaths of cancer in the United
States (26). Since approximately 1980, innovations in standard surgical treatment,
radiation therapy, and chemotherapy have resulted in only modest improvements in
survival from squamous cell carcinoma of the head and neck. The goal of research
directed at understanding the basic genetic mechanisms of head and neck cancer is to
increase the survival rate among persons with cancer of the head and neck.
Most malignant tumors among humans develop in a complex interaction between genetic
and environmental factors. At the most basic level, all cancers are genetic in that
development and progression occur because of accumulation of chromosomal and genetic
mutations. Four basic relationships can be identified: persons with genetic predisposition
for cancer but no environmental exposure, persons with environmental exposure but no
genetic predisposition, spontaneous mutations among persons who have neither genetic
predisposition nor environmental exposure, and persons with both genetic predisposition
and environmental exposure (27). There has long been evidence that squamous cell
carcinoma of the head and neck may have a genetic basis despite the existence of known
and multifactorial environmental influences (27,28 and 29). In families with smoking-
related malignant disease, genetic analysis supports an autosomal dominant inheritance
pattern (30). This genetic susceptibility also may explain why some persons with only
mild tobacco or alcohol exposure have squamous cell carcinoma of the head and neck,
whereas others with many times more use never do (27).
Loss or alteration of cell-cycle control is an intrinsic factor in the development of cancer.
Tumor suppressor genes are genes that have been identified as having regulatory control
of the cell cycle. When such regulatory forces are altered or lost because of mutational
events, cell-cycle control is changed. Poorly regulated or prolific cell growth can occur,
and cancers can develop.
Oncogenes are genes that have been causally identified with the development of cancer.
An example is the RET oncogene. Germline mutations in RET, located on chromosome
10q11.2, have been identified in families that manifest hereditary medullary carcinoma of
the thyroid (31). Identification of RET mutations is used as screening for multiple
endocrine neoplasia type 2b and familial medullary carcinoma of the thyroid. Because
early identification and management of medullary carcinoma of the thyroid markedly
affect outcome and survival, genetic screening of patients and their close relatives has
become a critical part of the diagnosis and management of medullary carcinoma of the
thyroid. In most cancer types, both loss of tumor suppressor genes and oncogene
activation occur. The former is believed to be more important than the latter for
squamous cell carcinoma of the head and neck (32). Many of the known oncogenes and
tumor suppressor genes are common to many cancers, and identification of a genetic
abnormality in one tumor type often is relevant to others.
Some persons are more susceptible to cancer because they are heterozygous for a tumor
suppressor or oncogene mutation. Because a single, inherited altered gene already is
present in a diploid cell (one hit), only the remaining normal gene copy has to mutate for
cancer to develop (two hits). Without the original hereditary abnormality, development of
cancer is less likely because two acquired mutations would have to occur. This premise
has been shown to be true for some cancers. Retinoblastoma occurs in both heritable and
sporadic patterns. Sporadic retinoblastoma is unilateral (30). Persons with the hereditary
form have loss or mutation and inactivation of a tumor suppressor gene called Rb1. These
persons have a hereditarily determined single hit. The likelihood that retinoblastoma will
develop is nearly 50%, and these lesions often are bilateral. Fifty percent of offspring are
susceptible to the cancer. The RB1 tumor suppressor gene helps to regulate transcription
of other genes and thus is involved in regulation of the cell cycle. Insertion of a normal
RB1 gene can result in a return of normal cell regulation (33).
Cytogenetics has been used in the study of squamous cell carcinoma of the head and neck
(34,35). Several chromosomal abnormalities have been identified. Oncogenes and tumor
suppressor genes are presumed to be located at the breakpoints of these deletions,
amplifications, and translocations. Common chromosomal abnormalities identified in
squamous cell carcinoma of the head and neck include 3p-, believed to be an early
chromosomal change in squamous cell carcinoma of the head and neck; 11q13
rearrangements, the location of the cyclin D1 oncogene (36); and 9p21-22, the site of cell
cycle gene p16 (32). Loss of 18q is likely related to advanced disease and carries a poor
prognosis (36,37). Other chromosomal losses include 5q, 8p, and 13q,17p.
Amplifications include 3q, 5q, and 11q. Cancer cells can be haploid (half the normal
DNA content), diploid (two times the normal DNA content), or tetraploid (four times the
normal DNA content). Aneuploidy (abnormal DNA content) is a feature of many cancer
cells. It is believed to be caused by altered proliferation of tumor cells and to reflect
aggressive clinical behavior (38). Ploidy analysis, however, has not shown any prognostic
factors and has done little to help identify the nature of head and neck cancer (38).
The cell-cycle gene most widely studied in relation to cancer among humans is the tumor
suppressor gene p53, found on chromosome 17p. The p53 protein helps to control the cell
cycle by binding with cyclin-dependent kinins to arrest cell replication in G1 (39). This
allows the cell to repair any DNA damage or mutations that have occurred. If DNA repair
fails, p53 can induce apoptosis or programmed cell death (36). Loss of activity of p53
results in an increase in the number of chromosomal abnormalities (40). This loss of p53
occurs in more than half of instances of squamous cell carcinoma of the head and neck.
For patients with a p53 abnormality in the index tumor, p53 can be evaluated at the
margins of the tumor at the time of resection. The presence of mutant p53 at the margins
is predictive of recurrence, even if the margins appear normal at light microscopic
examination (41). It is likely that the presence of p53 is related to early genetic changes
in squamous cell carcinoma, such as the conversion of normal mucosa to dysplastic
mucosa. Although p53 overexpression has been found to be predictive of a favorable
response to chemotherapy and organ preservation protocols, p53 expression has not been
found to be predictive of survival from squamous cell carcinoma of the head and neck
(36).
Cyclin D1, located at chromosome 11q13, is the most frequently amplified
protooncogene in squamous cell carcinoma of the head and neck. This oncogene product
accelerates cell cycle progression. Overexpression correlates with advanced disease and
reduced overall and disease-free survival rates (32). The p16 gene product is an inhibitor
of cyclin pathways and cyclin D1 and therefore is involved in cell cycle regulation.
Inactivation of p16 is one of the earliest genetic events in squamous cell carcinoma of the
head and neck (32).
The bcl family gene products are involved in cell cycle regulation and apoptosis. The bcl-
2 gene product inhibits apoptosis by blocking p53 dependent pathways. Overexpression
of bcl-2 has been linked to resistance to chemotherapy. The bax gene encodes an
inhibitor of bcl-2. Bcl-xL prevents apoptosis; bcl-xs promotes apoptosis (36).
Epidermal growth factor, epidermal growth factor receptor, and transforming growth
factor are growth factor gene products frequently overexpressed in squamous cell
carcinoma of the head and neck. None has been shown to be a reliable prognostic
indicator or tumor marker for recurrence (32).
Squamous cell carcinoma of the head and neck arises from a clonal population of cells
that have acquired many genetic alterations in a several-step process (34). Unlike the
colon cancer model, in which an orderly sequence of genetic events leads from adenoma
to metastatic carcinoma (42), it is likely that the genetic mutations in squamous cell
carcinoma of the head and neck do not necessarily follow one rigid sequence.
Nonetheless, certain genetic changes are believed to occur early and can be found in
dysplastic tissue. Others occur late and reflect invasive squamous cell carcinoma. A
possible progression of genetic changes for squamous cell carcinoma of the head and
neck is depicted in Fig. 2.10.

FIGURE 2.10. A sequence of genetic changes in
squamous cell carcinoma of the head and neck. This
scheme does not imply that abnormalities arise in the
sequence shown; each may be independent of the
appearance of the others. It is becoming more evident,
however, that some changes are associated with more
advanced stages of the disease and likely also with
important clinical factors, such as patient survival. Some
chromosomal changes, such as loss of the short arm of chromosome 3 (3p-) and p53
mutations appear to occur early in the development of squamous cell carcinoma of the
head and neck. They may have little effect on the progression to more advanced stages.
Other changes, such as loss of the long arms of chromosomes 5 and 18 (5q-and 18q-)
appear to occur later and may be related to greater invasiveness or increased risk of
recurrence and metastasis.



CONCLUSION
Advances in understanding human genetics allow more precise diagnosis of medical
disorders. Molecular methods increasingly allow diagnosis before the appearance of
symptoms or even prenatally. The possibility of genetic recurrence should be addressed
in the management of any inherited disorder, and counseling should be offered. As
knowledge of pathogenesis is gained, many genetic disorders may become amenable to
therapy, either medically, through gene product replacement, or through novel means of
gene manipulation.

HIGHLIGHTS
The human genome consists of approximately 3 billion base
pairs of nuclear DNA and 16,500 base pairs of mitochondrial
DNA that form genes that encode 80,000 proteins.
The three main patterns of mendelian genetic transmission are
autosomal dominant, autosomal recessive, and sex-linked.
Some disorders occur with increased frequency in families but
do not display classic mendelian transmission; these are said to
display multifactorial inheritance.
Some genetic disorders arise from a single gene mutation.
Others occur as a result of abnormalities of chromosome
number or structure.
The ability to isolate cloned genes has had great effect on our
understanding of the molecular basis of human genetic
disorders.
Molecular techniques can be used in the diagnosis of some
genetic disorders, by means of either direct detection of
mutations or genetic linkage analysis.
Genetic counseling involves familiarizing a family with the
medical facts about a disorder, the pattern of heredity, and
options for dealing with genetic risk and helping the family
adjust to dealing with the disorder.
Otolaryngologists encounter a wide variety of genetic disorders.
Some of these are well-known congenital syndromes with
multiple clinical features. We are recognizing that disorders
such as hearing loss and head and neck cancer can have genetic
etiologic components.
Genetic evaluation and intervention have increasing importance
in the diagnosis and management of disorders of the ears, nose,
throat, head, and neck.
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5. Shapira S. An update on chromosome deletion and microdeletion syndromes. Curr Opin Pediatr
1998;10:662627.
6. Schmickel RD. Contiguous gene syndromes: a component of recognizable syndromes. J Pediatr
1986;109:231241.
7. Webber SA, Hatchwell E, Barber JCK, et al. Importance of microdeletions of chromosomal region
22q11 as a cause of selected malformations of the ventricular outflow tracts and aortic arch: a
three-year prospective study. J Pediatr 1996;129:2632.
8. Chinnery PF, Elliott C, Green GR, et al. The spectrum of hearing loss due to mitochondrial DNA
defects. Brain 2000;123:8292.
9. Willems PJ. Genetic causes of hearing loss. N Engl J Med 2000;342:11011109.
10. Warren ST. The expanding world of trinucleotide repeats. Science 1996;271:13741375.
11. Wieringa B. Myotonic dystrophy reviewed: back to the future? Hum Mol Genet 1994;3:17.
12. Hall JG. Genomic imprinting: review and relevance to human disease. Am J Hum Genet
1990;46:857.
13. Deal CL. Parental genomic imprinting. Curr Opin Pediatr 1995;7:445458.
14. Strachan T, Read AP. Human molecular genetics. New York: BIOS Scientific Publishers, 1996.
15. Gleich LL. Gene therapy for head and neck cancer. Laryngoscope 2000;110:708726.
16. Clayman GL, El-Naggar AK, Lippman SM, et al. Adenovirus-mediated p53 gene transfer in
patients with advanced recurrent head and neck squamous cell carcinoma. J Clin Oncol
1998;16:22212232.
17. Fraser FC. Genetic counseling. Am J Hum Genet 1974;26:636.
18. Lalwani AK, Castelein DM. Cracking the auditory genetic code: nonsyndromic hereditary hearing
impairment. Am J Otol 1999;20:115132.
19. Tassabehji M, Newton VE, Leverton K, et al. PAX3 gene structure and mutations: close analogies
between Waardenburg syndrome and splotch mouse. Hum Mol Genet 1994;3:10691074.
20. Preus M, et al. Waardenburg syndrome: penetrance of major signs. Am J Med Genet 1983;15:383
388.
21. Smith RJH, Berlin CI, Hejtmancik JF, et al. Clinical diagnosis of Usher syndromes. Am J Med
Genet 1994;50:3238.
22. McKusick V. Mendelian inheritance in man, 9th ed. Baltimore: Johns Hopkins University Press,
1990.
23. Coyle B, Coffey R, Armour JAL, et al. Pendred syndrome (goitre and sensorineural hearing loss)
maps to chromosome 7 in the region containing the nonsyndromic deafness gene DFNB4. Nat
Genet 1996;12:421423.
24. Barker DF, Hostikka SL, Zhou J, et al. Identification of mutations in the COL4A5 collagen gene
in Alport syndrome. Science 1990;248:12241227.
25. Gubler MC, Knebelmann B, Beziau A, et al. Autosomal recessive Alport syndrome:
immunohistochemical study of type IV collagen chain distribution. Kidney Int 1995;47:1142
1147.
26. Benninger MS. Presentation and evaluation of patients with epidermoid head and neck cancers.
Henry Ford Hosp Med J 1992;40:144148.
27. Hart TC. Applications of molecular epidemiology to head and neck cancer. Otolaryngol Clin
North Am 1997;30:2134.
28. Cooper MP, Jovanovic A, Nauta JJ, et al. Role of genetic factors in the etiology of squamous cell
carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1995;121:157160.
29. Foulkes WD, Brunet JS, Kowalski LP, et al. Family history of cancer is a risk factor for squamous
carcinoma of the head and neck: a case-control study from Brazil. Am J Hum Genet 1995;57
A63:334.
30. Knudson A. Genetics of tumors of the head and neck. Arch Otolaryngol Head Neck Surg
1995;119:735737.
31. Chi DD, Moley JF. Medullary thyroid carcinoma. Surg Oncol Clin N Am 1998;7:681706.
32. Rowley H. The molecular genetics of head and neck cancer. J Laryngol Otol 1998;112:607612.
33. Hussussian CJ, Struewing JP, Goldstein AM, et al. Germline p16 mutations in familial melanoma.
Nat Genet 1994;8:1521.
34. Carey TE, Van Dyke DL, Worsham MJ. Nonrandom chromosomes aberrations and clonal
populations in head and neck cancer. Anticancer Res 1993;13:25612568.
35. Van Dyke DL, Worsham MJ, Benninger MS, et al. Recurrent cytogenetic abnormalities in
squamous cell carcinoma of the head and neck region. Genes Chromosomes Cancer 1994;9:192
206.
36. Bradford C. Predictive factors in head and neck cancer. Hematol Oncol Clin North Am
1999;13:777785.
37. Pearlstein RP, Benninger MS, Worsham MJ, et al. Preliminary study of 18q loss of heterozygosity
and poor survival in patients with stage III head and neck cancers. Online Int J Otolaryngol
1997;2FA:18.
38. Wolf GT, Fisher SG, Truelson JM, Beals TF. DNA content and regional metastases in patients
with advanced laryngeal squamous cell carcinoma. Laryngoscope 1994;104:479483.
39. Pavelic ZP, Gluckman JL. The role of p53 tumor suppressor gene in human head and neck
tumorigenesis. Acta Otolaryngol (Stockh) 1997[Suppl 527]:2124.
40. Knudson A, Field JK, Pavelic ZP, et al. The role of p53 tumor suppressor gene in squamous cell
carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1993;119:11181122.
41. Brennan JA, Mao T, Hruban RH, et al. Molecular assessment of histopathological staging in
squamous cell carcinoma of the head and neck. N Engl J Med 1995;332:429435.
42. Benninger MS, Worsham MJ, Van Dyke DL. Genetics of squamous cell carcinoma of the head
and neck region. In: English G, ed. Otolaryngology, vol 5. Philadelphia: JB Lippincott, 1997:1
28.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

3 ADVANCES IN MOLECULAR BIOLOGY
Head & Neck SurgeryOtolaryngology
3




ADVANCES IN MOLECULAR BIOLOGY
MICHAEL FRIEDMAN
JESSICA W. LIM

M. Friedman: Section of Head and Neck Surgery, Rush Medical College, Rush-PresbyterianSt. Luke's
Medical Center, Chicago, Illinois.
J.W. Lim: Department of OtolaryngologyBronchoesophagology, Rush-PresbyterianSt. Luke's Medical
Center, Chicago, Illinois.


Head and Neck Cancer
B-cell Lymphoma/Leukemia-2 Gene
p53
Human Papillomavirus
Thyroid Cancer
Salivary Gland Neoplasms
Otologic Disease
Acoustic Neuroma
Otitis Media
Hearing Loss
Chapter References
The discovery of the DNA double-helix structure by Watson and Crick in 1953 was the
most important step toward understanding genetics, protein regulation, and normal cell
function. As technology advanced beyond the gross and histologic levels, the cell and its
underlying genetic machinery became targets for exploration. It is well established that
disease essentially begins at the gene level, and resulting aberrations in gene product
expression are what are presented to clinicians. Molecular biology techniques developed
for the detection and manipulation of proteins, RNA, and DNA are now commonly used
in research directed at the diagnosis and understanding of an array of diseases. The field
of hereditary deafness, for example, has benefited from the development of advanced
genetic techniques. Further discoveries in the molecular pathogenesis of diseases will
allow physicians to improve prevention, diagnosis, prognosis, and treatment. This chapter
provides a brief description of recent advances in molecular biology within
otolaryngology.
HEAD AND NECK CANCER
Cancer has long been suspected to be a disease ultimately caused by the loss of genetic
control. In the last several years, many studies have identified genetic markers that can be
used in the prognosis of cancers in the breast, lung, and other sites. The search for gene
markers in head and neck cancer lagged. Recent studies have identified markers that may
serve as prognostic factors in the management of head and neck cancer.
Normal cell life is regulated by specific genes that code for a variety of proteins that
affect homeostasis. Alterations in genes that regulate cellular proliferation,
differentiation, and apoptosis (programmed cell death) differentiate neoplastic cells from
normal cells. Gene alterations can occur in several ways, such as genome damage by
means of mutation or deletion, imprinting, chromosomal rearrangement, or mitotic
recombination. Gene activity also can be affected by interaction with viral oncoproteins
or carcinogens. In general, any such changes can cause aberrant gene expression and
tumorigenesis.
The regulatory genes can be divided into two main categories. Protooncogenes encode
proteins that stimulate cellular proliferation. In most cases, they code for growth factors,
receptors, and other molecules involved in signal transduction pathways or for
transcription factors that regulate gene expression. Oncogenes are protooncogenes that
have a mutation that causes malignant transformation when they are inappropriately
expressed. Tumor suppressor genes normally hinder the growth of uncontrolled cell
proliferation driven by oncogenes. The double-hit theory of cancer development holds
that both alleles of a tumor suppressor gene must be inactivated for the cell to proliferate.
These abnormal cells thus are allowed to reproduce and expand unchecked.
Several gene regulators have been identified, particularly in regard to squamous cell
carcinoma. The function of these genes typically is evaluated indirectly by means of
detection of the associated gene product. Continued identification of specific genes, gene
products, and their roles in tumor regulation may lead to new preventive techniques,
improved diagnostic capabilities, reliable prognostic markers, and specific treatment
strategies.
B-cell Lymphoma/Leukemia-2 Gene
The B-cell lymphoma/leukemia-2 gene (bcl-2) is a tumor-suppressor gene and primary
regulator of apoptosis. Normal bcl-2 expression inhibits apoptosis and counteracts the
effects of p53. The bcl-2 proteins are present predominantly in the mitochondrial
membrane and have been found in a variety of tissues, including lymphoid tissue,
bronchial epithelium, skin, intestine, breast, prostate, thyroid, and nasopharynx (1).
Under healthy conditions, bcl-2 proteins are present only in the basal or proliferating cells
of these tissues.
The expression of bcl-2 protein has been studied in tumors of the breast, lung, and
prostate as well as in tumors of the head and neck. Although bcl-2 is a relative newcomer
to the group of recognized gene markers, it is emerging as a marker of clinical
significance. Numerous studies have been performed to identify other gene markers, such
as p53, as prognostic indicators. None of the investigators found consistent, statistically
relevant predictors of outcome.
In early studies, Friedman et al. (2) identified bcl-2 as a highly sensitive marker for
predicting prognosis in early squamous cell carcinoma of the larynx. This was especially
important because the group of patients who participated in the study included those
treated with either radiation or surgery alone. In a retrospective study of early-stage
squamous cell carcinoma of the head and neck (T1N0 or T2N0 glottic larynx; T1N0 oral
cavity, pharynx, supraglottic larynx), overexpression of bcl-2 correlated with a
significantly reduced cure rate, 50% versus 90%, which is expected in the management of
these localized lesions. There was no significant difference in recurrence rate with regard
to treatment modality (surgery or radiation therapy).
Other studies have shown similar results among patients treated with radiation only.
Gallo et al. (3) conducted a study with a group of patients who had tumors of the head
and neck at all sites; 70% of the tumors were located in the larynx. The investigators
showed that overexpression of bcl-2 correlated with a shortened disease-free interval and
decreased overall survival rate. These results are greatly encouraging but not conclusive.
In a study involving 70 patients with squamous cell carcinoma of the larynx and several
tumor markers identified, bcl-2 was not a prognostic discriminator (4). Additional studies
by Friedman et al. (5) showed that bcl-2 is not a prognostic indicator in advanced
laryngeal carcinoma.
Two mechanisms have been suggested by which disordered bcl-2 expression can cause
resistance to treatment and shorter survival times. Overexpression of bcl-2 may prevent
spontaneous apoptosis and lead to more rapid accumulation of tumor cells for a given
proliferation rate. Spontaneous apoptosis is known to be an important factor in tumor-
volume doubling time. Another possibility is that bcl-2 confers resistance to therapy by
blocking treatment-related apoptosis. Radiation therapy and chemotherapy are directed at
inducing apoptosis.
The prognostic significance of bcl-2 overexpression alone may not apply to all tumors. In
one study, patients with squamous cell carcinoma of the lung and overexpression of bcl-2
had a better survival rate than those not expressing bcl-2 (6). A similar observation was
reported for breast cancer (7). These contradictory findings may be the result of different
methods of assessing bcl-2 expression, but the more likely explanation may involve the
influence of other closely related gene products, such as bax, bcl-sl, bcl-xs, and bad (8).
For example, bcl-2 is thought to function largely by means of antagonizing the cell
deathinducing effect of bax. If bax expression is somehow impaired, cancer cells may
be resistant to apoptosis even in the presence of very low levels of bcl-2. Abnormalities
of bax expression have been documented for breast cancer (8). Assessing the family of
related genes instead of bcl-2 alone in squamous cell carcinoma of the head and neck
may make it easier to ascertain who will have a poor response to standard treatment.
p53
The p53 tumor suppressor gene is responsible for arrest in the cell cycle after genetic
injury. It allows the cell to repair the DNA defect before the next cell division. The gene
also induces apoptosis. Alteration in the p53 gene locus is the most commonly identified
genetic mutation in squamous cell carcinoma of the head and neck and in all types of
cancer among humans.
Mutations of p53 and overexpression of p53 protein have been found in approximately
40% of invasive squamous cell carcinomas of the head and neck and in more than 50% of
malignant neoplasms of the mouth (9). Overexpression of p53 also has been observed in
dysplasia and carcinoma in situ of the larynx (10). Cigarette smoking is known to cause
p53 mutations (11). Squamous cell carcinomas with p53 mutations are more common
among persons who smoke and among those who drink heavily. The mutations among
these persons have been found over a broad area of the chromosome, rather than at
limited sites, as is characteristic of spontaneous mutations in abstainers. Mutations of the
p53 gene are less frequent among patients with squamous cell carcinoma who are older
than 75 years than among those 40 to 70 years of age (12). This finding implies that
squamous cell carcinoma of the upper aerodigestive tract among elderly patients may be
a result of a longer period of exposure to genetic injuries from spontaneous mutation or
environmental factors combined with an aging repair process. Koch et al. (12) found a
loss of heterozygosity of markers on a number of chromosomal arms in specimens of
squamous cell carcinoma. This finding indicated the possible involvement of several
suppressor genes.
Overexpression of p53 has had mixed results as a prognostic factor. In a review of T1
squamous cell carcinoma of the floor of the mouth and ventral tongue, no statistically
significant correlation was found between the level of p53 expression and tumor
aggressiveness (13). In contrast, a review of oropharyngeal squamous cell carcinoma
specimens showed that p53 protein was predictive of increased risk of death
independently of tumor grade, stage, and lymph node status (14). Expression of p53
seems to correlate with a poor prognosis, particularly in advanced squamous cell
carcinoma of the head and neck. The full negative effect of overexpression p53 may
occur only very late in disease, thus correlating with survival in end-stage disease. The
function of p53 protein can be interrupted with viral oncoprotein binding, such as the E6
protein of human papillomavirus types 16 and 18, and thus potentiate carcinogenesis
(15).
Human Papillomavirus
Human papillomavirus (HPV) has been linked to development of papilloma in the nose
and respiratory tract and to carcinogenesis in the genitourinary tract. Known oncogenic
types 16, 18, and 31 have been found in squamous cell carcinoma of the tongue, tonsil,
larynx, and pharynx. Human papillomavirus DNA was detected in 46% of archival tissue
specimens of laryngeal and hypopharyngeal carcinoma, and the presence of this DNA
appeared to correlate with a poorer prognosis than among cases in which there was no
detectable HPV (16). Portugal et al. (17) detected HPV (11%) and p53 mutation (66%)
within the same specimens of squamous cell carcinoma of the oral cavity and tonsil,
which showed that neither p53 gene mutation nor HPV infection serves as a
prognosticator of tumor behavior, although survival rates were higher among persons
with HPV-infected cancer of the tonsil (17). Among patients with a history of low
alcohol and tobacco use, HPV infection was an independent risk factor for squamous cell
carcinoma of the oral cavity and tonsil.
The exact role of HPV in carcinogenesis in the upper aerodigestive tract is unknown.
Binding of E6 HPV proteins to the p53 tumor suppressor gene may lead to gene product
degradation and unchecked cell proliferation. The E7 HPV protein is known to form
complexes with the retinoblastoma tumor suppressor gene product pRB, and this process
leads to tumorigenesis (18). No role for the retinoblastoma gene has been found in
squamous cell carcinoma of the head and neck. An association of HPV with mutated H-
ras oncogene has been suggested in squamous cell carcinoma of the mouth (19).
However, the ras oncogene group is infrequently involved in head and neck cancer (20).
Thyroid Cancer
Quantification of nuclear DNA in papillary carcinoma reveals a close correlation between
DNA ploidy and the aggressiveness of thyroid lesions (21). Two groups of patients have
been compared, one with noninvasive disease and another with invasion of the thyroid.
Forty percent of invasive lesions were aneuploid, whereas all tumors without such extent
were diploid. The thyroid has been considered an advantageous target for somatic gene
therapy because of its great capacity for protein synthesis, high blood flow, and
sensitivity to hormonal regulation. O'Malley et al. (22) developed a method for
transferring genes into cultured human thyroid follicular cells with the use of retroviral
vectors. Cells were transfected with either the LNL6 vector, carrying the gene for
neomycin resistance, or the zen-B-gal vector, carrying the -galactosidase marker. In this
experimental model, transfection rates ranged from 0.1% to 3%.
Salivary Gland Neoplasms
The factors of prognostic significance for salivary gland neoplasms are well known and
are based mainly on histologic features, including status of surgical margins, perineural
invasion, and lymph node metastasis as well as histologic type and grade. In the future,
prognostic indicators found at the gene level may provide the most accurate information.
DNA ploidy was examined as a prognostic indicator for adenoid cystic carcinoma in a
small series of 20 patients (23). All tumors with DNA aneuploidy recurred; only two of
the 14 DNA diploid lesions recurred. These results may have an effect on treatment
planning, particularly because DNA aneuploid tumors are more radiosensitive than are
DNA diploid tumors.
Overexpression of c-erb-b2 oncoprotein, a receptor of growth factors, in adenocarcinoma
of the major salivary glands may be an indicator of aggressiveness. In 59 cases of
malignant tumors of the major salivary gland that also included squamous cell, adenoid
cystic, and mucoepidermoid carcinoma, only adenocarcinoma produced a positive
staining result (24). The tumors with c-erb-b2 overexpression were more difficult to
resect, were associated with more frequent nodal metastasis, and resulted in a markedly
lower disease-free survival than did adenocarcinomas that did not show overexpression.
OTOLOGIC DISEASE
Acoustic Neuroma
Acoustic neuroma accounts for about 8% of all intracranial tumors. These tumors are
bilateral and familial in 4% of cases, a condition associated with neurofibromatosis type
2. The neurofibromatosis type 2 gene has been localized to chromosome 22. Genetic
analysis of both familial and sporadic acoustic neuroma has revealed frequent loss of
alleles at chromosome 22 in both types (25,26). Greater extent of chromosome 22
deletions was associated with larger tumor size, but this finding was not statistically
significant. Further work is being directed at identifying a prognostic indicator for tumor
aggressiveness.
Otitis Media
Clinical research suggests that susceptibility to microorganisms that cause acute otitis
media may be hereditary. Kalm et al. (27) tested for several human lymphocyte antibody
(HLA) antigens in patients with recurrent acute otitis media. HLA-A2 antigen was
present more frequently in the recurrent otitis media group than in controls, indicating the
existence of a relation between recurrent acute otitis and the HLA locus.
Hearing Loss
Nowhere has the development of molecular techniques had more consequence than with
hearing loss, particularly hereditary deafness. About 50% of congenital diseases of the
inner ear are genetically acquired. Genetic mapping relied mainly on kindred and linkage
analyses until the recent increase in the number of available genetic markers (see Chapter
2). Research in otolaryngology directed at the molecular level continues at an accelerated
pace. Future advances are certain to advance the understanding and management of
maladies such as cancer. Somatic gene therapy, with targeted gene inactivation and
insertional mutagenesis, ultimately may provide the means to alter disease.

HIGHLIGHTS
Pathogenesis, particularly the development of cancer, originates
with aberrations of normal cell regulation at the genetic level.
The development of techniques to manipulate genetic material
has allowed research into disease at the molecular level.
Alterations at the gene level may be caused in many ways, such
as spontaneous mutation, recombination error, infection by
viruses, or carcinogens.
Protooncogenes and tumor suppressor genes regulate normal
cell proliferation, differentiation, and apoptosis (programmed
cell death).
Bcl-2 appears to be a clinically significant prognostic gene
marker in squamous cell carcinoma of the head and neck.
Alteration in p53 is the most common gene mutation in
squamous cell carcinoma of the head and neck and in malignant
tumors throughout the body.
Prevention and management of disease lies with somatic gene
therapy.
CHAPTER REFERENCES
1. Hockenberry DM, Zutter M, Hickey W, et al. Bcl-2 protein is topographically restricted in tissues
characterized by apoptotic cell death. Proc Natl Acad Sci USA 1991;88:69616965.
2. Friedman M, Grey P, Venkatesan TK, et al. Prognostic significance of Bcl-2 expression in
localized squamous cell carcinoma of the head and neck. Ann Otol Rhinol Laryngol
1997;106:445450.
3. Gallo O, Boddi V, Calzolari A, et al. S. Bcl-2 protein expression correlates with recurrence and
survival in early stage head and neck cancer treated by radiotherapy. Clin Cancer Res 1996;2:261
264.
4. Spafford MF, Koeppe J, Pan Z, et al. Correlation of tumor markers p53, bcl-2, CD34, CD44H,
CD44v6, and Ki-67 with survival and metastasis in laryngeal squamous cell carcinoma. Arch
Otolaryngol Head Neck Surg 1995;122:627632.
5. Friedman M, Lim J, Manders E, et al. Prognostic significance of Bcl-2 and p53 expression in
advanced laryngeal squamous cell carcinoma. Head Neck 2000 (in press).
6. Pezzella F, Turley H, Kuzu I, et al. Bcl-2 protein in nonsmall-cell carcinoma. N Engl J Med
1993;329:690694.
7. Silvestrini R, Venerooni S, Daidone MG, et al. The Bcl-2 protein: a prognostic indicator strongly
related to p53 protein in lymph nodenegative breast cancer patients. J Natl Cancer Inst
1994;86:499504.
8. Reed JC, Miyashita T, Takayama S, et al. Bcl-2 family proteins: regulators of cell death involved
in the pathogenesis of cancer and resistance to therapy. J Cell Biochem 1996;60:2332.
9. Davidson BJ, Hsu TC, Schantz SP. The genetics of tobacco-induced malignancy. Arch
Otolaryngol Head Neck Surg 1993;119:11981205.
10. Field JK, Pavelic ZP, Spandidos DA, et al. The role of the p53 tumor suppressor gene in squamous
cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1993;119:11181122.
11. Brennan JA, Boyle JD, Koch WM, et al. Association between cigarette smoking and mutation of
the p53 gene in squamous cell carcinoma of the head and neck. N Engl J Med 1995;332:712717.
12. Koch WM, Patel H, Brennan J, et al. Squamous cell carcinoma of the head and neck in the elderly.
Arch Otolaryngol Head Neck Surg 1995;121:262265.
13. Gluckman JL, Pavelic ZP, Welkoborsky HJ, et al. Prognostic indicators for squamous cell
carcinoma of the oral cavity: a clinicopathologic correlation. Laryngoscope 1997;107:12391244.
14. Caminero JM, Nunez F, Suarez C, et al. Detection of p53 protein in oropharyngeal carcinoma.
Arch Otolaryngol Head Neck Surg 1996;122:769772.
15. Foster SA, Demers GW, Etscheild BG, et al. The ability of human papillomavirus E6 proteins to
target p53 for degradation in vivo correlates with their ability to abrogate actinomycin Dinduced
growth arrest. J Virol 1994;58:56985705.
16. Clayman GL, Stewart MG, Weber RS, et al. Human papillomavirus in laryngeal and
hypopharyngeal carcinomas. Arch Otolaryngol Head Neck Surg 1994;120:743748.
17. Portugal LG, Goldenberg JD, Wenig BL, et al. Human papillomavirus expression and p53 gene
mutations in squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 1997;123:12301234.
18. Brachman DG. Molecular biology of the head and neck. Semin Oncol 1994;21:320339.
19. Anderson JA, Irish JC, McLachlin CM, et al. H-ras oncogene mutation and human papillomavirus
infection in oral carcinomas. Arch Otolaryngol Head Neck Surg 1994;120:755760.
20. Leonard JH, Kearsley JH, Chenevix-Trench G, et al. Analysis of gene amplification in head-and-
neck squamous-cell carcinomas. Int J Cancer 1991;48:511515.
21. Stern Y, Lisnyansky I, Shpitzer T, et al. Comparison of nuclear DNA content in locally invasive
and noninvasive papillary carcinoma of the thyroid gland. Otolaryngol Head Neck Surg
1997;117:501503.
22. O'Malley BW, Adams RM, Sikes ML, et al. Gene transfer into human thyroid follicular cells.
Laryngoscope 1994;104:130136.
23. Franzen G, Klausen OG, Grenko RT, et al. Adenoid cystic carcinoma: DNA as a prognostic
indicator. Laryngoscope 1991;101:669673.
24. Sugano S, Mukai K, Tsuda H, et al. Immunohistochemical study of c-erb B-2 oncoprotein
overexpression in human major salivary gland carcinoma: an indicator of aggressiveness.
Laryngoscope 1992;102:923927.
25. Irving RM, Moffat DA, Hardy DG, et al. Molecular genetic analysis of the mechanism of
tumorigenesis in acoustic neuroma. Arch Otolaryngol Head Neck Surg 1993;119:12221228.
26. Sainz J, Baser ME, Ragge NK, et al. Loss of alleles in vestibular schwannomas. Arch Otolaryngol
Head Neck Surg 1993;119:12851288.
27. Kalm O, Johnson U, Prellner K, et al. HLA frequency in patients with recurrent acute otitis media.
Arch Otolaryngol Head Neck Surg 1991;117:12961299.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

4 PRINCIPLES OF PHARMACOLOGY AND MEDICAL THERAPY
Head & Neck SurgeryOtolaryngology
4




PRINCIPLES OF PHARMACOLOGY AND
MEDICAL THERAPY
RICHARD L. MABRY

R.L. Mabry: Department of Otolaryngology, University of Texas Southwestern Medical Center, Dallas,
Texas.


Diseases and Associated Conditions
Drugs of Choice
Characteristics and Actions of Drugs
Cost-Benefit Considerations
Responsible Antibiotic Selection
Administration and Duration of Therapy
Side Effects and Interactions
Risk of Teratogenic Effects
Antihistamines
Decongestants
Expectorants
Analgesics
Antibiotics
Conclusion
Chapter References
Although great strides have been made in surgical technology, some practitioners have
overemphasized the role of regional surgical specialists. It is common during residency to
focus on operative procedures, but on entering private practice, the fledgling
otolaryngologist sometimes is surprised by the need to master previously neglected
modes of medical therapy and by the infrequent summons to exercise surgical skills
honed in residency. As the 1980s were marked by surgical advances, the 1990s
emphasized recognition and medical management of disorders of the ear, nose, throat,
head, and neck. Even greater progress is anticipated in the new millennium. This chapter
offers general information and philosophical advice to enable clinicians to choose and
administer pharmacotherapy effectively for conditions in which medical therapy is
appropriate (Fig. 4.1).

FIGURE 4.1. Decision making in pharmacotherapy.



DISEASES AND ASSOCIATED CONDITIONS
It is important to establish a specific diagnosis before treating. If therapy is to do more
than relieve symptoms, the underlying cause of the problem must be identified and
controlled specifically. An exact diagnosis is necessary because some
pharmacotherapeutic agents are specific in action. For example, cromolyn is effective for
managing immunoglobulin Emediated allergic rhinitis but is ineffective in managing
vasomotor rhinitis and polyp disease. An exact diagnosis also is important because the
presence of unrecognized, complicating factors can diminish or negate the effectiveness
of therapy. For example, nasal decongestant sprays can cause complicating rhinitis
medicamentosa. A corollary to this rule is that if treatment must be administered without
a specific diagnosis, the therapeutic response to the medication may render a clue to the
proper diagnosis. Not all patients with infection need a culture and sensitivity study, but
the response or lack thereof to the antibiotic empirically chosen is useful information for
further treatment of the patient.
Establishing an accurate diagnosis on which to base treatment means there rarely is
justification for shotgun therapy, that is, using enough drugs in the regimen to hit
everything. An unfortunate example is the practice of some physicians who treat
patients with nasal problems with an antibiotic for infection, an antihistamine for allergy,
a decongestant for congestion, and a nasal steroid for nonspecific antiinflammatory
effect. Such polypharmacy is expensive, is wasteful of medical resources, exposes
patients to unneeded medications, to which allergies may develop or which may
encourage bacterial resistance, and is entirely inappropriate.
The coexistence of medical conditions other than the one for which the patient is being
treated affects the treatment chosen. Physicians must be aware of the medical status of
patients and their current medications. For example, patients with diabetes mellitus may
need more prolonged antibiotic therapy for an infection than may patients without
diabetes. Patients with labile hypertension may respond to systemic decongestants with
additional elevations of blood pressure. Patients taking tricyclic antidepressants or
monoamine oxidase inhibitors may display a greater vasopressor response to such
decongestants because of potentiation by these compounds.
DRUGS OF CHOICE
Dr. Hueston King first acquainted me with the adage, To one who is good with a
hammer, most things resemble a nail. The proliferation of pharmacologic agents is
difficult to follow, and physicians often develop a routine treatment of patients who have
a certain set of signs and symptoms. New medications may have no benefit over existing
ones, but wise practitioners should be familiar with the standard medications for
managing common otolaryngeal disorders and be receptive to new agents as they are
made available. This means that the physician's armamentarium is constantly changing
on the basis of reliable new information.
Characteristics and Actions of Drugs
A classic example of the difficulty in discerning the correct drug is in the choice of
antibiotics. In no other form of pharmacotherapy has such a continuing explosion of
available preparations occurred. By classifying drugs as members of a particular class,
such as penicillins, macrolides, cephalosporins (first-, second-, third-, and fourth-
generation), and quinolones, and becoming familiar with the general characteristics of the
class, physicians can discern more easily the advantages and disadvantages of new
preparations as they appear. Even more important is the problem of drug resistance and
the mechanism by which this occurs for various antibiotics. This situation is constantly
evolving. Physicians need to examine new data as they become available and must
remain familiar with the incidence and patterns of antibiotic resistance in their particular
geographic areas.
Cost-Benefit Considerations
Even in these days of managed care, with drugs often available to patients for only a
nominal copayment, fiscal and social responsibility necessitates that physicians consider
drug cost. On the other hand, the most expensive antibiotic is the one that does not work,
and the physician's experience and knowledge of community pathogen patterns of drug
sensitivity can be helpful, as can the judicious use of cultures when previous therapy has
failed. Table 4.1 lists the cost of antibiotics commonly used in otolaryngology.

TABLE 4.1. RELATIVE COSTS OF VARIOUS
ANTIBIOTICS USED IN OTOLARYNGOLOGY



The least expensive antibacterial agents are those that can be obtained as generic
preparations, although unfortunately marked drug resistance can develop by the time
these antibiotics become available in generic form. Parenteral antibiotics are much more
expensive than those administered orally, and are rarely indicated in an outpatient setting.
An obvious exception is the prescription of intravenous vancomycin for culture-proven
methicillin-resistant staphylococci.
Responsible Antibiotic Selection
The increasing prevalence of antibiotic-resistant bacteria (Fig. 4.2, Fig. 4.3) is leading to
new approaches in managing common respiratory infections in the outpatient setting (1).
Failure of empiric therapy may necessitate culture of, for example, a specimen obtained
from the middle meatus, to direct further antibiotic selection. Indiscriminate prescription
of broad-spectrum antibiotics for trivial indications undoubtedly promotes the
development of drug-resistant bacteria. Infectious disease experts recommend initial use
of agents based on community experience and switching from broad- to narrow-spectrum
drugs as soon as microbiologic confirmation allows (2).

FIGURE 4.2. Increasing incidence of penicillin-resistant
Streptococcus pneumoniae infection in the United States
since 1979.



FIGURE 4.3. Increasing prevalence of -lactamase-
mediated resistance of Haemophilus influenzae to
ampicillin in the United States in 1983.



The multiple factors involved in the choice of an antibacterial drug are summarized in
Fig. 4.4. Further complicating decision making is the variety of mechanisms by which
therapeutic effectiveness is assessed in vitro, such as area under the concentration-time
curve and minimum inhibitory concentration (Fig. 4.5). To most physicians, these are
unfamiliar terms, rarely mentioned during residency. Nevertheless, the practitioner must
become familiar with these terms and apply them to particular antibiotics as they are
introduced to decide whether the new drug offers any advantage over existing
preparations. Physicians should avoid practices that hasten development of drug
resistance, such as prescribing antibiotics for trivial indications, underdosing or
administration for an inadequate length of time, and allowing periods of insufficient drug
concentration.

FIGURE 4.4. Factors involved in choice of antimicrobial
therapy. Bacterial killing is influenced by a drug with a
pharmacokinetic profile that delivers sufficient
concentration to the infection site to exceed the minimum
inhibitory concentration for the pathogen in question.



FIGURE 4.5. Methods of considering antibacterial
efficiency, depending on the drug under consideration,
include relation of peak concentration to minimum
inhibitory concentration (MIC), area under the curve in
relation to MIC, and time at which concentration of drug
exceeds MIC.



ADMINISTRATION AND DURATION OF THERAPY
Administration and duration of therapy depend on the condition for which the patient is
being treated. In general, parenteral therapy is used only if the manner of drug
administration or the severity of illness makes oral therapy impractical or ineffective. For
conditions such as otitis externa and rhinitis, some preparations are better administered
topically than they are systemically. For example, corticosteroids administered
intranasally rather than systemically are less likely to cause serious side effects, and the
effect is concentrated in the desired area.
Duration of therapy varies with the condition for which the patient is being treated, but
the usual tendency is to prescribe antibiotics for too short a period, often leading to
recurrence or failure of full resolution of the infection. Many antibiotics now have
specific time-length recommendations for specific diseases, such as acute sinusitis or
chronic bronchitis. Other therapies administered for chronic disorders, such as steroid
nasal sprays for chronic allergic rhinitis, must be monitored to prevent the patient from
making them a lifelong habit with the attendant potential side effects and complications.
In all instances, the physician must observe the patient and use response to therapy as a
guide to duration of treatment.
SIDE EFFECTS AND INTERACTIONS
Information gained during drug development (Table 4.2) and contained in sources such
as the Physician's Desk Reference, USP Drug Information for the Health Care
Professional, and package inserts alerts physicians about side effects and drug
interactions. This information base grows as rapidly as the list of new drugs. For this
reason, many physicians are turning to commercially available products, available in hard
copy or computer format, that serve as guides to drug interactions and adverse effects.
One such source is Drug Interactions, available from the U.S. Pharmacopoeia.

TABLE 4.2. DRUG DEVELOPMENT AND
APPROVAL PROCESS OF THE U.S. FOOD AND
DRUG ADMINISTRATION (FDA)



Numerous drug interactions have been determined. Failure to be aware of these
interactions has severe consequences. Monoamine oxidase inhibitors and tricyclic
antidepressants potentiate the effect of direct- and indirect-acting adrenergic agents. With
monoamine oxidase inhibitors, this potentiation can be seen for as long as 14 days after
the compounds are discontinued. Therefore, -adrenergic agents should be used with
caution and in lower doses than usual to treat patients taking either of these preparations.
-Blocking agents are commonly prescribed. Patients taking these preparations are more
prone to anaphylactic reactions, as from medications, bee stings, and allergy
immunotherapy, than the general population. The reactions often are refractory to
conventional therapeutic measures such as injection of epinephrine.
An interaction often not appreciated is that of some antibiotics with oral contraceptives.
Many drugs, including some macrolide antibiotics, tetracyclines, metronidazole,
penicillins, and trimethoprim-sulfamethoxazole can decrease the effectiveness of oral
contraceptives. The patient should be informed of her increased risk of pregnancy and
advised to use other methods of contraception for at least one menstrual cycle beyond
cessation of such antibiotic therapy (3).
Potentially life-threatening cardiac arrhythmias associated with prolongation of the QT
interval have followed administration of the antihistamines terfenadine or astemizole with
other drugs metabolized by the cytochrome P-450 enzyme system. Although both these
drugs are now off the U.S. market, the fact that this interaction did not come to light for
several years after the introduction of these preparations should signal caution to every
physician. This problem emphasizes the importance of reporting adverse drug reactions
when they occur. Reporting agencies such as the U.S. Pharmacopoeia monitor these
reports and issue warnings when appropriate.
RISK OF TERATOGENIC EFFECTS
In prescribing for every female patient from menarche to menopause, it is prudent to ask
about the last normal menstrual period to avoid prescribing a preparation that may harm
an early pregnancy. As a practical matter, drug-induced fetal abnormalities are fairly rare.
When they do occur, however, they represent a catastrophic event. In the general
population, the incidence of serious major fetal malformation is 2% to 3%. This
percentage encompasses defects incompatible with life, such as anencephaly, or those
necessitating extensive surgical correction, such as cleft palate or cardiac defects. If the
definition of malformation is broadened to include minor malformations, such as
supernumerary digits, the rate approaches 7% to 10% of all births, drug exposure
accounting for 2% to 3% of this group. Although the incidence of drug-related birth
defects is low, we must strive to keep that percentage as close to zero as possible. As
Neibyl (4) stated, Humans are not rats. Although almost all research involving the
effects of drugs on a developing fetus is conducted with laboratory animals, the length of
pregnancy and the time of development of various fetal parts differ radically between
humans and rats. Nevertheless, the U.S. Food and Drug Administration has adopted
labeling categories for drug use in pregnancy based on human and animal experience
(Table 4.3). In general, pregnant patients should be treated with preparations that have the
best record of safety. Consultation with the obstetrician may be necessary.

TABLE 4.3. U.S. FOOD AND DRUG
ADMINISTRATION (FDA) LABELING
CATEGORIES FOR DRUG USE IN PREGNANCY



The so-called teratogenic period in human pregnancy spans the time from approximately
31 days after the last menstrual period through the tenth week after the last period. In
other words, at about the time of the first missed period and for the next 6 weeks or more,
drugs administered to a pregnant woman, who may not realize that her menstrual
irregularity signals pregnancy, may affect vital areas of fetal development. The brain
continues to develop until birth, and drugs given throughout pregnancy may affect it.
Antihistamines
Most antihistamines are not considered teratogenic. The best-controlled study with
human subjects involved chlorpheniramine. This drug was shown not to increase the risk
of birth defects in a series of more than 1,000 exposures in the first trimester. Triprolidine
also was shown to be safe in a smaller series. A study involving 65 exposures to
brompheniramine in the first trimester showed a threefold increase in the relative risk of
birth defects associated with this common antihistamine, which is available by
prescription and in over-the-counter preparations. Safety for use during pregnancy of the
newer nonsedating antihistamines remains a subject of conjecture, although preliminary
studies of administration of cetirizine and loratadine to animals are reassuring (5).
Decongestants
Epinephrine and phenylpropanolamine are associated with a substantial increase in risk
of birth defects if administered during the first trimester, but pseudoephedrine has not
shown any teratogenicity. Topical nasal decongestants are safer in that they have less
severe systemic effects, but the risk of habituation and rebound rhinitis during pregnancy
is higher than during the nonpregnant state.
Expectorants
Expectorant preparations containing iodides should be avoided because of the potential
effect on fetal thyroid function, but guaifenesin is a safe and effective expectorant with
no demonstrated teratogenicity. Some over-the-counter cough syrups contain large
amounts of alcohol, as much as 25%. Repetitive consumption of these preparations,
especially in amounts higher than the recommended doses, can have serious effects on
both mother and fetus.
Analgesics
No clear answers have been obtained from the few studies of the use of analgesics during
pregnancy. Aspirin is not recommended. It can reduce clotting capability, and its
antiprostaglandin effect may decrease the effectiveness of uterine contractions. To a
lesser extent, the same can be said of the numerous nonsteroidal antiinflammatory agents.
Codeine has little teratogenic risk. In addition to the side effect of constipation,
compounding a problem that often exists in pregnancy, there is risk of addiction.
Propoxyphene is probably the analgesic of choice for moderate to severe pain during
pregnancy. In a prospective study, 686 first-trimester exposures to propoxyphene were
associated with a 4.5% incidence of fetal malformation, a figure indicating that the
teratogenic potential of propoxyphene is not great. Because the addiction risk of this drug
has been established, including rare instances of neonatal withdrawal symptoms among
infants of addicted mothers, propoxyphene should not be used for trivial indications.
Antibiotics
No teratogenicity has been demonstrated for the antibiotics commonly used in the
management of otolaryngeal infections; however, some special factors deserve mention.
During pregnancy, as a result of increased renal clearance and maternal blood volume,
serum levels of amoxicillin and cephalosporins after administration are lower than those
achieved in the nonpregnant state. Erythromycin apparently is not teratogenic. Its
absorption and passage across the placenta are unpredictable. Except for reversible
hepatic dysfunction associated with the estolate form, no serious undesirable side effects
of the drug preclude its use in pregnancy.
Sulfonamides apparently have no deleterious effects on the fetus, but in the blood of
neonates, they compete with bilirubin for binding sites on albumin, raising the level of
free bilirubin in the serum and increasing the risk of kernicterus. Although long-acting
sulfonamides and trimethoprim combined with sulfamethoxazole have caused congenital
anomalies in animals, controlled trials with humans have not shown any teratogenic risk
associated with these compounds. Tetracycline administered during pregnancy can retard
skeletal growth and produce discoloration of the deciduous teeth. Clindamycin apparently
presents no potential danger to the fetus.
CONCLUSION
Although the available modalities for medical management of problems encountered in
otolaryngology are continually expanding and improving, the principles of application
remain relatively constant. After the diagnosis is established, the drug most specific for
the management of the disorder should be chosen. Factors such as cost-benefit ratio
should be considered in the decision. The route and duration of administration must be
individualized and altered according to the response obtained. The physician must be
aware of side effects and the drug interactions possible because of the patient's general
medical status and other medications taken. Pharmacotherapy during pregnancy or to
treat women who may become pregnant during therapy necessitates an even broader
range of knowledge of the effects of the medication chosen.

HIGHLIGHTS
Establishing an accurate diagnosis improves therapeutic
efficiency.
Unrecognized, complicating factors and concomitant disease
can diminish or negate the effectiveness of therapy.
Some pharmacotherapeutic agents are specific in action and
may be effective only for certain conditions.
A knowledge of the mechanism of action of specific drugs, and
of risk of drug resistance in the case of antibiotics, is important
in selecting agents.
Newer pharmacotherapeutic agents can pose disadvantages as
well as advantages over existing drugs.
If two or more agents yield equivalent results, the cost to the
patient should be considered.
Preparations available in a generic form can be as much as ten
times less expensive than a brand name preparation, but an
inexpensive drug that is ineffective is no bargain.
The route of administration and total length of treatment must
be individualized.
Physicians must be aware of interactions and side effects of
every drug they prescribe and must update their knowledge as
new preparations become available.
For treatment of pregnant patients, preparations with the best
record of safety should be chosen. The clinician must have a
full knowledge of the effects on mother and fetus and should
consult with the obstetrician.
CHAPTER REFERENCES
1. Fairbanks DNF. Antimicrobial therapy. In: Otolaryngologyhead and neck surgery, 9th ed.
Washington, DC: American Academy of Otolaryngology-Head and Neck Surgery, 1999.
2. Green M, Wald ER. Emerging resistance to antibiotics: impact on respiratory infections in the
outpatient setting. Ann Allergy Asthma Immunol 1996;77:167175.
3. The Medical Letter Handbook of Adverse Drug Reactions. New Rochelle, NY: Medical Letter,
2000.
4. Niebyl JR, ed. Drug use in pregnancy, 2nd ed. Philadelphia: Lea & Febiger, 1988.
5. American College of Allergy Asthma and Immunology. The use of newer asthma and allergy
medications during pregnancy (position statement). Ann Allergy Clin Immunol 2000;84:475480.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

5 MICROBIOLOGY, INFECTIONS, AND ANTIBIOTIC THERAPY
Head & Neck SurgeryOtolaryngology
5




MICROBIOLOGY, INFECTIONS, AND
ANTIBIOTIC THERAPY
DAVID N. F. FAIRBANKS

D.N. F. Fairbanks: Department of Otolaryngology, George Washington University School of Medicine,
Washington, D.C.


Antimicrobial Agents
Penicillins
Cephalosporins
Other -Lactam Antibiotics
Macrolides
Clindamycin
Tetracyclines
Chloramphenicol
Quinolones, Fluoroquinolones
Vancomycin
Metronidazole
Aminoglycosides
Rifampin
Sulfonamides
Treatment Strategies
Otitis Media
Sinusitis
Pharyngitis
Tonsillitis
Laryngitis
Epiglottitis
Croup
Wounds
Mastoiditis
Suppurative Otitis
Prophylaxis
Chapter References
Recommended Reading
This chapter is an overview of the antimicrobial agents most commonly used against the
bacteria that cause infections of the ears, nose, throat, head, and neck. Because new
bacterial resistance and new antibiotics appear regularly, this information should be
supplemented with that in The Medical Letter on Drugs and Therapeutics, The Medical
Letter Handbook of Antimicrobial Therapy, and the latest editions of The Sanford Guide
to Antimicrobial Therapy, and the Pocket Guide to Antimicrobial Therapy in
OtolaryngologyHead and Neck Surgery (1,2 and 3).
ANTIMICROBIAL AGENTS
Penicillins
Penicillins belong to the -lactam family of antibiotics, so named because of the -lactam
molecular ring in their chemical composition. Because of the differing uses, it is
instructive to consider them by categories.
Penicillins G and V are highly active against Streptococcus pyogenes (-hemolytic group
A), Streptococcus pneumoniae (most strains), actinomycosis, and a dwindling proportion
of oral anaerobic organisms. They are inactivated by penicillinase produced by
Staphylococcus aureus and other enzymes produced by a variety of gram-negative
organisms, such as Haemophilus influenzae, Moraxella catarrhalis, and oral anaerobic
organisms. These enzymes are collectively called -lactamases, and they render many of
the penicillin and cephalosporin agents inactive. Through a different mechanism, related
to protein binding rather than enzymes, S. pneumoniae is becoming increasingly resistant
to the penicillins and cephalosporins. Intermediate-level resistance may yet allow
effective treatment with high doses of amoxicillin or second- and third-generation
cephalosporins, but highly or multiply resistant strains are resistant to all penicillins, most
cephalosporins, macrolides, tetracyclines, clindamycin, and chloramphenicol. Because
gastric acid exerts an adverse effect on penicillins G and V, they are best administered on
an empty stomach (1 hour before a meal).
Rashes occur among 5% of persons who take penicillin. They do not entirely preclude
future use of penicillin because rashes recur among only 50% of these patients. When
they are retreated with penicillin, these patients usually need little more than
antihistamine treatment. Anaphylaxis is a different reaction, and it does not necessarily
occur among patients with previous rash reactions. Because it is life threatening,
anaphylaxis is considered a lifelong contraindication to future use of penicillin. All
penicillins carry the same risk of causing anaphylaxis.
Antistaphylococcal penicillins resist penicillinase. Methicillin, oxacillin, cloxacillin,
dicloxacillin, and nafcillin are agents in this category. Dicloxacillin attains the highest
blood levels of any of the orally administered antistaphylococcal penicillins. Nafcillin is
preferred for intravenous use, especially to treat patients with renal impairment, because
it can be excreted through the liver. These agents are highly effective against Staph.
aureus, even penicillin-resistant strains, except for a troublesome newcomer called
methicillin-resistant staphylococcus, the prevalence of which reaches 10% of the
staphylococcal strains in some hospitals. This organism is resistant to all penicillins and
all cephalosporins. Except for methicillin, antistaphylococcal penicillins are active
against streptococcal and most pneumococcal infections.
Aminopenicillins, such as ampicillin and amoxicillin, extend the activity spectrum to
gram-negative organisms such as Proteus organisms, Escherichia coli, and H. influenzae,
but Staph. aureus is resistant to drugs in this category. Furthermore, -lactamase
enzymes produced by 20% to 30% of H. influenzae strains and most strains of M.
catarrhalis cause resistance to these agents. Aminopenicillins produce rashes more
commonly than do other penicillins, especially if the patient has infectious
mononucleosis (50% incidence of rash). Amoxicillin attains higher levels in the serum
and middle ear fluid than does ampicillin, and it is well absorbed orally at meal times.
Augmented penicillins are those in which the penicillin is combined with an agent that
inactivates resistance-producing -lactamase enzymes. For the management of infection
by staphylococci, H. influenzae, M. catarrhalis, anaerobic organisms, and others,
amoxicillin is combined with potassium clavulanate (Augmentin, oral), and ampicillin is
combined with sulbactam (Unasyn, parenteral). For the management of Pseudomonas
aeruginosa infection and a broad spectrum of other infections, ticarcillin is combined
with potassium clavulanate (Timentin, parenteral).
Antipseudomonal penicillins are active against most gram-negative bacteria but not
gram-positive organisms, such as Staph. aureus. The activity of these agents against P.
aeruginosa separates them from most other antibiotics. They are administered
parenterally. Ticarcillin is more active than is carbenicillin. Piperacillin is the most active
of all drugs in this category. In the management of serious pseudomonal infection, these
drugs often are used in combination with an aminoglycoside, such as gentamicin, for a
synergistic effect.
Cephalosporins
Cephalosporins also belong to the -lactam family of drugs. This chemical relation
probably means that patients with a history of penicillin anaphylaxis should avoid
cephalosporins; however, cephalosporins are commonly and safely used by patients with
a history of penicillin rashes. These drugs are categorized into first, second, and third
generations. In general, first-generation agents are most active against gram-positive
bacteria, and third-generation agents are highly active against gram-negative bacteria.
Second-generation agents occupy an intermediate position. It is easiest to be familiar with
one oral agent and one or two parenteral agents in each generation. For information about
other agents, see the Pocket Guide to Antimicrobial Therapy (2).
First-generation oral cephalexin (Keflex) is highly effective against gram-positive
organisms such as streptococci, pneumococci except for penicillin-resistant strains, and
staphylococci except the methicillin-resistant strains. It is also active against a few gram-
negative bacteria, but Staph. aureus is the organism against which it is most commonly
used. For parenteral use, cefazolin (Ancef, Kefzol) produces the longest duration of
action of the first-generation agents. Its antistaphylococcal activity is widely used in
prophylaxis against surgical infections after operations in which a skin incision is made.
Second-generation cefuroxime is available for both parenteral (Zinacef) and oral (Ceftin)
use. Both are highly active against gram-positive cocci, but more important, they are
effective against H. influenzae and M. catarrhalis, including the ampicillin-resistant
strains. Pneumococci resistant to penicillin (intermediate level) can be controlled with
cefuroxime or similar agents, such as cefprozil (Cefzil) or cefpodoxime (Vantin), but
these agents are ineffective against high-level resistant pneumococci. Cefpodoxime and
loracarbef (Lorabid) are so similar to cefuroxime in activity and use that for simplicity
they can be considered second-generation equivalents. As oral preparations, these agents
are useful in managing acute sinusitis and otitis media. For intracranial complications of
acute sinusitis or otitis media, cefuroxime penetrates the blood-brain barrier fairly well.
Third-generation cephalosporins include three of special importance in the management
of infections of the ear, nose, throat, head, or neck. Cefixime (Suprax) is an oral agent
highly active against H. influenzae and M. catarrhalis, even the ampicillin-resistant
strains. Acute sinusitis and otitis media caused by these organisms can be managed
effectively with once-daily dosing in a tablet or suspension preparation. If treatment fails,
the infection probably is pneumococcal, against which this third-generation agent is less
effective than are the first- and second-generation agents. Ceftibutn (Cedax) is roughly
equivalent to cefixime.
Ceftriaxone (Rocephin) is a parenteral agent effective against H. influenzae, M.
catarrhalis, S. pneumoniae, including most penicillin-resistant strains, Neisseria
meningitidis, and Neisseria gonorrhoeae. Because it penetrates into the cerebrospinal
fluid and because it has a broad spectrum of activity against organisms that cause upper
respiratory infections, ceftriaxone usually is the first choice for treating patients with
intracranial and orbital complications of acute sinusitis and otitis media. It is also the first
choice for treating patients with oral gonococcal infections. Ceftriaxone has been found
useful for single-dose injection therapy for acute and subacute otitis media. In many
respects, cefotaxime (Claforan) is an equivalent agent. Ceftazidime (Fortaz) is a
parenteral agent highly active against P. aeruginosa. It is also active against other gram-
negative bacteria, including H. influenzae and N. gonorrhoeae, and it penetrates well into
the cerebrospinal fluid. In general, third-generation cephalosporins are less active against
gram-positive bacteria, such as Staph. aureus, than are their first-generation counterparts.
Anaerobic bacteria, such as Bacteroides fragilis, also are relatively resistant.
Other -Lactam Antibiotics
Imipenem (combined with cilastatin in Primaxin) and meropenem (Merrem) are
parenteral agents that exert a broad spectrum of antimicrobial activity. They are active
against S. pyogenes, most S. pneumoniae organisms, Staph. aureus (except methicillin-
resistant strains), H. influenzae, B. fragilis and most anaerobic organisms, and the
coliforms, including P. aeruginosa. Because of its broad spectrum, imipenem or
meropenem can be used as a single agent against infection by unidentified organisms, but
cerebrospinal fluid penetration is not assured. Because resistance can appear during
therapy for pseudomonal infections, a -lactam agent should not be used as a single
agent. Patients with penicillin allergies may be allergic to imipenem. Aztreonam
(Azactam) is a parenteral agent active against aerobic gram-negative organisms such as
P. aeruginosa. Its distinguishing feature is its safety in the treatment of patients with
penicillin allergies.
Macrolides
Erythromycins are effective therapy for respiratory infections due to streptococci, most
pneumococci, mycoplasmata, and chlamydiae, legionellosis, diphtheria, and pertussis.
Most Staph. aureus infections are susceptible to erythromycins, but resistance can
develop during therapy. Management of H. influenzae infection with erythromycins is
effective if a sulfonamide is added to the regimen (the combination Pediazole).
Pneumococci resistant to penicillin are likely resistant to macrolides as well.
Preparations have been devised to minimize the degree of nausea and vomiting that
accompanies use of erythromycin. The ethylsuccinate preparation can be taken with
meals. Others need enteric coatings. Newer macrolides such as azithromycin (Zithromax)
and clarithromycin (Biaxin) are more tolerable in terms of gastrointestinal effects. More
important, they extend their antimicrobial activity to include H. influenzae and M.
catarrhalis. Erythromycins and clarithromycin elevate theophylline levels with
stimulating side effects if the drugs are taken concomitantly.
Clindamycin
Clindamycin (Cleocin, oral or parenteral) is highly active against gram-positive cocci,
including many but not all strains of penicillin-resistant pneumococci. Clindamycin is
especially effective in the management of Staph. aureus infection, including infection
with many methicillin-resistant strains. It is also highly effective against anaerobic
infections of the aerodigestive tract, particularly with B. fragilis, which causes infection
deep in the neck and draining ears and causes septic shock. Osteomyelitis is successfully
managed with clindamycin because the organism is concentrated in bone. The
combination of clindamycin and gentamicin is effective prophylaxis against all the
common contaminants of surgical wounds, such as Staph. aureus, P. aeruginosa, and
anaerobic organisms.
Nausea or diarrhea is sometimes intolerable after oral administration. Pseudomembranous
colitis due to overgrowth of enteric Clostridium difficile is a serious complication
attributed to clindamycin, but it also can complicate therapy with many other broad-
spectrum agents. Treatment requires oral metronidazole or vancomycin. Patients who
need clindamycin may be pretreated for several days with metronidazole to prevent
colitis.
Tetracyclines
Tetracyclines are effective against Mycoplasma, Chlamydia, and Legionella infections.
Most streptococcal, staphylococcal, and H. influenzae infections are resistant to
tetracyclines, which means these drugs should be recommended only after culture studies
show susceptibility of the infecting organisms. Because tetracyclines stain enamel in
forming teeth, use of these agents is avoided in the care of children younger than 10 years
and of women who may be pregnant. Tetracyclines predispose users to sunburn. Milk
products and antacids (calcium, magnesium) interfere with absorption.
Chloramphenicol
Chloramphenicol (Chloromycetin, oral and intravenous) exerts broad-spectrum activity
against gram-positive cocci, including most penicillin-resistant Staph. aureus, and most
gram-negative bacteria, including H. influenzae and the anaerobic organisms of the
aerodigestive tract. Pseudomonas organisms, however, are resistant, as are penicillin-
resistant strains of pneumococci. Chloramphenicol penetrates readily into the
cerebrospinal fluid. Fatal bone marrow depression occurs among 1 of 24,000 patients
who take chloramphenicol. This limits its use to management of life-threatening infection
when other effective agents are unavailable, as in intracranial extension of sinusitis or
otitis media in a patient with a history of anaphylactic reaction to -lactam agents, such
as penicillin.
Quinolones, Fluoroquinolones
The quinolone-fluoroquinolone group of antibiotics has a broad spectrum of
effectiveness. They are useful in the management of infections that are resistant to several
drugs. They have the additional advantage of being structurally unrelated to other classes
of antibiotics, so they may be used to treat patients who are allergic to penicillins,
sulfonamides, erythromycin, or cephalosporins.
Ciprofloxacin (Cipro) and ofloxacin (Floxin) are called antipseudomonas quinolones.
They are important because of their effectiveness in controlling P. aeruginosa infection
when given orally. Ciprofloxacin has greater therapeutic potency and causes fewer
adverse side effects than does ofloxacin. Both agents elevate theophylline levels if such
drugs are taken concomitantly. Ciprofloxacin has been effective in the treatment of
patients with cystic fibrosis who have bronchitis, of those with pseudomonal sinusitis,
and of those with malignant necrotizing otitis externa.
Levofloxacin (Levaquin), trovafloxacin (Trovan), gatifloxacin (Tequin), moxifloxacin
(Avelox), and gemifloxacin (Factive) are classified as respiratory quinolones and are
useful in the management of respiratory and pharyngeal infections. They are effective
against -hemolytic S. pyogenes, S. pneumoniae, including penicillin-resistant strains,
and Staph. aureus, including methicillin-resistant strains. They also are active against H.
influenzae and M. catarrhalis, including -lactamase-producing strains, and against
atypical pathogens such as Mycoplasma, Chlamydia, Legionella, and Bordetella pertussis
organisms. They have the advantage of being long acting, so once-a-day dosing is
effective. They are best absorbed if taken 1 hour before milk, antacids, or vitamin
preparations that contain minerals.
Gatifloxacin, moxifloxacin, and trovafloxacin are the more potent antibiotics in this
group. They are also active against anaerobic organisms such as Bacteroides and
Peptostreptococcus. Because of reported adverse reactions, including liver damage,
trovafloxacin preparations have been removed from the market. Intravenous
trovafloxacin is used primarily in cases of severe or life-threatening infections, such as
meningitis, when there are no other good options.
Vancomycin
Vancomycin (Vancocin, parenteral) is highly active against gram-positive cocci,
including methicillin-resistant strains of Staph. aureus, penicillin-resistant strains of
pneumococci, enterococci, and gonococci. Because it is unrelated to any other class of
antibiotics, vancomycin is useful in the treatment of patients with penicillin allergies.
High concentrations in the serum of patients with renal impairment can cause ototoxicity.
Vancomycin does not cross the blood-brain barrier effectively, so when resistant
pneumococcal infections extend intracranially, vancomycin therapy should be combined
with ceftriaxone or trovafloxacin. Because vancomycin may be the last remaining agent
still effective against highly resistant strains of staphylococci, pneumococci, and
enterococci, this drug should be reserved for such serious infections and not used against
bacteria that can be effectively controlled with other antimicrobial agents.
Metronidazole
Metronidazole (Flagyl, oral or parenteral) is highly active against anaerobic bacteria,
including B. fragilis. It is useful in management of oral infections. All aerobic bacteria
are resistant to this agent, but combination therapy (metronidazole plus any of the
penicillins, cephalosporins, or quinolones) can be recommended to manage deep neck
abscesses, chronic sinusitis, draining cholesteatoma, and intracranial extension of these
infections. Metronidazole penetrates the blood-brain barrier well. Against antibiotic-
induced pseudomembranous enterocolitis, metronidazole is much less expensive than
vancomycin and is the preferred choice. Alcohol should not be consumed by patients
taking metronidazole lest a reaction such as that to disulfiram (Antabuse) occurs.
Aminoglycosides
Systemic aminoglycosides are administered by the parenteral route only. Gentamicin,
tobramycin, and amikacin are used against P. aeruginosa and other hospital-acquired
infections, such as Serratia infection. Gentamicin (generic) is inexpensive and usually is
used as the first-choice agent in this category unless resistance is expected and the
infection is progressing rapidly. Resistance to gentamicin does not necessarily imply
resistance to tobramycin and amikacin, which are used as alternatives. For serious
pseudomonal infection, treatment is improved if aminoglycosides are combined with
antipseudomonal penicillins, such as tobramycin plus ticarcillin. These combinations
produce a synergistic effect that reduces resistance or retards its emergence.
Anaerobic infections are almost universally resistant to aminoglycosides, as are 10% or
more of Staph. aureus infections. A combination of gentamicin with clindamycin
eliminates this problem. This combination is highly effective in the management of head
and neck wounds with mixed infections and deep neck infections, and it provides
excellent prophylaxis against surgical wound infections.
Ototoxicity of these agents places constraints on parenteral use, particularly of
streptomycin, kanamycin, and neomycin. The incidence of aminoglycoside ototoxicity
for gentamicin, tobramycin, and amikacin is commonly stated as approximately 10%, but
it is worse among patients with impaired renal function, which allows toxic serum levels
to accumulate. Careful monitoring indicates the dosages needed to avoid ototoxicity (2).
Rifampin
Rifampin is an important oral agent for managing the nasopharyngeal carrier state of H.
influenzae and meningococcus. In combination with other antistaphylococcal drugs, such
as ciprofloxacin, it controls resistant Staph. aureus and resistant pneumococci. It is
sometimes combined with clindamycin or a second-generation cephalosporin. Mupirocin
(Bactroban) ointment plus oral rifampin is useful in the management of chronic
staphylococcal infection of the nostrils.
Sulfonamides
Sulfonamides are older agents effective in the management of H. influenzae infection but
not of pneumococcal, streptococcal, and staphylococcal infections; however,
sulfonamides may be used in combination with penicillin, cephalexin, macrolides
(erythromycins), or even clindamycin to broaden the antimicrobial spectrum of coverage
of these agents. Sulfonamides commonly cause rashes and photosensitivity (sunburn).
Sulfamethoxazole plus trimethoprim (Bactrim, Septra) in combination is more potent
than either agent alone.
TREATMENT STRATEGIES
The physician's choice of antimicrobial agent is influenced by the following factors: (a)
probable infecting organism, site of infection, and community prevalence, (b) probability
of resistance to agent, (c) patient intolerance or allergy to agent, and (d) cost of agent. For
example, amoxicillin may be an inexpensive first choice to manage acute otitis media,
but it is not for the approximately 10% of patients with infections by organisms resistant
to the drug. For physicians or patients who would be highly dissatisfied with the
possibility of a treatment failure, one of the more expensive alternatives may be a better
first choice. Physician and patient preferences and special situations may take precedence
over the general recommendations listed in Table 5.1. Most well-established acute
infections necessitate 10 days of therapy. Treatment begun very soon after the onset of
infection may be of shorter duration. Chronic infection may necessitate several weeks or
months of treatment and may not clear without surgical drainage.

TABLE 5.1. DRUGS OF CHOICE ACCORDING TO
CLINICAL DIAGNOSIS



Otitis Media
Acute otitis media is caused by S. pneumoniae, H. influenzae, or M. catarrhalis, also
known as Branhamella catarrhalis. Amoxicillin controls most strains of S. pneumoniae,
but more than 20% of strains of H. influenzae are resistant, as are more than 80% of
strains of M. catarrhalis. Erythromycin plus sulfonamide is slightly more expensive than
amoxicillin, but it is more likely to clear the infection because it covers all the pathogens
except penicillin-resistant pneumococci. Amoxicillin with clavulanate also is used to
control the common pathogens, as are cefuroxime, cefprozil, and cefpodoxime. Cefixime
can be administered once a day in a pleasant-tasting suspension for management of H.
influenzae and M. catarrhalis infection, but failures are probable caused by
pneumococcal resistance. Ceftibuten is similar to cefixime.
Penicillin-resistant pneumococci are prevalent pathogens among children who have
received prolonged low-dose antimicrobial prophylaxis and those exposed to other
children in large day-care centers. They pose special treatment problems. In a study
conducted in New York City, investigators found pneumococcus in 26% (31 of 115) of
middle ear aspirates from children with otitis media (4). Nonsusceptible strains were
identified in 16% of the pneumococcal infections, and only cefuroxime had consistent
activity against the moderately resistant strains. Another set of investigators (5)
emphasized the growing prevalence of penicillin-resistant S. pneumoniae and its
association with the use of two or more antibiotics to manage pediatric upper respiratory
tract infections. The authors emphasized the need for continuing education of primary
care physicians.
Intermediate-level resistance usually responds to amoxicillin with or without clavulanate,
especially if dosages are high. An alternative is to administer ceftriaxone by means of
injection. High-level resistance necessitates vancomycin therapy or possibly a quinolone
frequently used to manage respiratory tract infectionlevofloxacin, gatifloxacin,
moxifloxacin, or gemifloxacin. Chronic otitis media with effusion is caused by the same
pathogens as acute otitis media and is managed with the same antimicrobial agents.
Sinusitis
Acute sinusitis is caused by the same bacteria as acute otitis media. Drug choices are the
same; however, if sinusitis extends intracranially, pneumococcal infection is suspected,
and agents must be selected that penetrate the blood-brain barrier, such as ceftriaxone,
cefuroxime, or trovafloxacin. Orbital extension implies impending central nervous
system extension, and it is similarly managed. Chronic sinusitis is caused by a mixture of
various anaerobes that frequently includes Staph. aureus. Clindamycin or amoxicillin-
clavulanate is a rational choice. Various fungi and Pseudomonas organisms in extensive
polyposis also may be causative. Itraconazole (Sporanox) controls fungi. Ciprofloxacin
controls Pseudomonas infection.
Pharyngitis
Pharyngitis is caused by S. pyogenes among 30% of persons with sore throats during the
winter months as ascertained with throat culture studies; however, N. gonorrhoeae,
Mycoplasma, Chlamydia, and Haemophilus organisms are other important causes of sore
throat that can be controlled with antimicrobial therapy. Other likely agents are the
anaerobic organisms involved in tonsillitis. Diphtheria is rare. All of these organisms
produce negative strep cultures of the throat, which illustrates the folly of routinely
withholding antibiotic therapy until strep culture results prove positive. Clinical judgment
is required. Factors that favor bacterial infection and the need for antibiotic treatment
include (a) a history of bacterial infection in the household, (b) prolonged or severe sore
throat, (c) severe erythema, exudate, or lymphadenopathy, (d) absence of hoarseness,
which indicates viral laryngitis.
Tonsillitis
Tonsilloadenoiditis is most frequently caused by S. pyogenes, but a variety of anaerobic
organisms often are present in a mixed infection. These commonly produce -lactamase
enzymes that render penicillin ineffective even against the streptococci. Therefore,
clindamycin often is more effective. Augmented amoxicillin also is effective, but if
mononucleosis is the principal infection, amoxicillin has a 50% probability of producing
a severe rash. Clindamycin, cephalexin, or penicillin plus metronidazole can avoid that
problem. Extensive exudate on the tonsils suggests mononucleosis among adolescents
and children. Antibiotic therapy may not control Epstein-Barr virus, but it does control
secondary bacterial invaders.
Laryngitis
Acute laryngitis usually is a viral infection that resolves with a few days of voice rest.
Prolonged hoarseness suggests a secondary bacterial infection to be controlled with
erythromycin or another macrolide plus sulfonamide or a quinolone commonly used to
manage respiratory tract infection.
Epiglottitis
Epiglottitis is most frequently caused by H. influenzae. Parenterally administered
sulbactam-ampicillin, cefuroxime, or ceftriaxone is a rational choice. Trovafloxacin
administered intravenously can be used to treat patients with a history of penicillin
anaphylaxis. Airway management takes priority.
Croup
Croup (subglottic) usually is a viral infection, but 10% of patients have secondary
infections with Staph. aureus or H. influenzae. If thick yellow secretions are encountered,
administer the same agents as used for epiglottitis.
Wounds
Deep neck abscesses and wounds subjected to mucosal infection or chronic intracranial
infection of ear or sinus origins are caused by mixed bacterial flora with anaerobic
organisms predominating. Clindamycin covers Staph. aureus, all cocci, and anaerobic
organisms, but when pseudomonal infection is suspected, gentamicin should be added.
Neither of these agents, however, reliably penetrates into central nervous system tissues,
for which nafcillin plus metronidazole is needed. If Haemophilus or pseudomonal
infection is anticipated, ceftazidime can be administered. Trovafloxacin administered
intravenously and vancomycin are contingency drugs for patients with a history of
penicillin anaphylaxis.
Mastoiditis
Management of acute mastoiditis with subperiosteal abscess requires coverage of the
same microbial possibilities as acute otitis media. Pneumococci and H. influenzae tend to
intracranial extension. Ceftriaxone is the initial choice. Chronic suppurative
otomastoiditis, including cholesteatoma, adds Staph. aureus, Proteus organisms, B.
fragilis, and other anaerobic organisms to the infectious polymicrobial mix. Smelly pus
suggests the presence of anaerobic bacteria. Pseudomonas also is a frequent contaminant.
Intracranial extension necessitates use of combinations that penetrate the central nervous
system, such as ceftazidime plus augmented ampicillin or ceftazidime plus metronidazole
plus nafcillin.
Suppurative Otitis
Ototopical therapy is only as effective as the cleanings the physician provides, because
infection advances in the opposite direction as the drainage flows. The draining ear of
acute otitis externa or suppurative otitis media necessitates combination drug therapy
polymyxin for the pseudomonal infection and neomycin for the Staph. aureus, Proteus
organisms, and others. Either of these agents alone is likely to produce treatment failure;
Cortisporin or Coly-Mycin S includes both. Some Pseudomonas organisms are resistant
to polymyxin, but gentamicin drops can be added to or alternated with the Neosporin-
polymyxin preparation. Quinolone otic drops such as ciprofloxacin and ofloxacin are
highly effective, and they are particularly indicated in the treatment of patients with a
tympanic membrane that is not intact. In a study involving 381 patients with chronic
suppurative otitis media, investigators found that Pseudomonas organisms (27%) and
Staph. aureus (24%) were the important organisms isolated. Topical aural preparations of
ciprofloxacin and gentamicin were the most effective agents (6).
Otomycosis due to Aspergillus infection usually is managed with acidifying ear drops
that contain acetic or boric acid, such as Acetasol and Domeboro. Other antiseptics, such
as Merthiolate, gentian violet, and iodine, sometimes are used. Topical antifungal agents,
such as clotrimazole (Lotrimin) work for candidiasis. Tom (7) reported that according to
results of studies of animals, clotrimazole, miconazole, and tolnaftate appear to be safe in
terms of ototoxicity, but gentian violet can cause severe damage. The residue left by the
nystatin preparation is cause for concern and a reminder that both the active ingredient
and the vehicle must be considered in terms of safety.
Prophylaxis
If cellular tissue levels of properly selective antibiotics are high at the moment of
contamination, such as incision, surgical wound infections and sepsis are remarkably
reduced. Prophylaxis for surgical wound infections requires administration of the initial
dose an hour or so before incision time and continuation for 24 hours or until the period
of wound contamination, such as suture line leakage, has passed. For incisions through
the skin, staphylococcal infection must be addressed, and cefazolin is the most commonly
used agent. Incisions through mucous membranes, especially pharyngeal membranes, can
cause contamination by anaerobic organisms. Wound breakdown among hospitalized
patients carries risk of pseudomonal infection. Gentamicin plus clindamycin covers all
these contingencies. This prophylaxis yields excellent results in head and neck tumor
surgery. Postoperative infection associated in uninfected nasal or otologic operations are
so uncommon that statistical proof of the efficacy of prophylaxis is unlikely. If
prophylaxis is justified, it is by inference from its effectiveness in surgical procedures in
general. If the risk of a serious or poor outcome outweighs the risk or cost of
administration of antibiotics, treatment may be advisable.

HIGHLIGHTS
Acute otitis media and acute sinusitis usually are caused by S.
pneumoniae, H. influenzae, or M. catarrhalis.
The prevalence of pneumococcal infection resistant to
penicillin, amoxicillin, and cephalosporin is increasing.
Treatment may necessitate use of vancomycin or levofloxacin.
Most cases of acute sinusitis or otitis media can be managed
with amoxicillin with or without clavulanate; macrolides with
or without sulfonamides; cefuroxime; cefprozil; cefpodoxime;
or ceftriaxone.
Orbital or intracranial extension of acute otitis media or
sinusitis can be managed with ceftriaxone.
Chronic sinusitis and deep neck abscesses are polymicrobial
infections that contain anaerobic organisms; clindamycin and
amoxicillin-clavulanate are effective.
Surgical wound infections can be caused by staphylococcal,
pseudomonal, and occasionally anaerobic organisms;
gentamicin plus clindamycin is effective.
Pharyngitis can be caused by a variety of controllable
organisms in addition to streptococci. Macrolides
(erythromycins) are effective.
Tonsillitis often is a polymicrobial infection that must be
managed with cephalosporin or clindamycin.
Pseudomonal infections can be managed with intravenous
ceftazidime or oral ciprofloxacin, both of which are
nonototoxic.
Respiratory quinolones (levofloxacin, gatifloxacin,
moxifloxacin) exert broad-spectrum activity against
Staphylococcus, Streptococcus, Mycoplasma, Chlamydia,
Haemophilus, and Moraxella organisms.
CHAPTER REFERENCES
1. Gilbert DN, Muellering RC, Sande MA. The Sanford guide to antimicrobial therapy. Hyde Park,
VT: Antimicrobial Therapy.
2. Fairbanks DNF. Pocket guide to antimicrobial therapy. In: Otolaryngologyhead and neck
surgery, 9th ed. Alexandria, VA: American Academy of OtolaryngologyHead and Neck
Surgery, 1999.
3. The medical letter handbook of antimicrobial therapy. The Medical Letter Inc. New Rochelle, NY.
4. Haddad J Jr, Saiman L, Chin NX, et al. Penicillin-nonsusceptible pneumococcus in acute otitis
media in New York City. Otolaryngol Head Neck Surg 1999;121:27.
5. Shapiro NL, Pransky SM, Martin M, et al. Documentation of the prevalence of penicillin-resistant
Streptococcus pneumoniae isolated from the middle ear and sinus fluid of children undergoing
tympanocentesis or sinus lavage. Ann Otol Rhinol Laryngol 1999;108:629.
6. Indudharan R, Haq JA, Aiyar S. Antibiotics in chronic suppurative otitis media: a bacteriologic
study. Ann Otol Rhinol Laryngol 1999;108:440.
7. Tom LWC. Ototoxicity of common topical antimycotic preparations. Laryngoscope
2000;110:509.
RECOMMENDED READING
Johnson JT, Yu VL. Infectious diseases and antimicrobial therapy of the ears, nose and throat.
Philadelphia: WB Saunders, 1997.
McCracken GH. Recent perspectives on drug resistant Streptococcus pneumoniae. Pediatr Infect Dis J
1996;15[Suppl]:930965.
Paradise JL. Managing otitis media: a time for change. Pediatrics 1995;96:712715.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

6 DIAGNOSTIC IMAGING
Head & Neck SurgeryOtolaryngology
6




DIAGNOSTIC IMAGING
ARNOLD M. NOYEK
IAN J. WITTERICK
DANIEL M. FLISS
EDWARD E. KASSEL

A.M. Noyek and I.J. Witterick: Department of Otolaryngology, Mt. Sinai Hospital, Toronto, Ontario,
Canada.
D.M. Fliss: Department of OtolaryngologyHead and Neck Surgery, Sourasky Medical Center, Tel Aviv,
Israel. E.E. Kassel: Department of Medical Imaging, Mount Sinai Hospital and University Health
Network, Toronto, Ontario, Canada.


Principles of Imaging
Imaging Modalities
Conventional Imaging
High-technology Imaging
Head and Neck Radiology by Region
Temporal Bone
Paranasal Sinuses
Soft Tissues of the Neck
Larynx
Salivary Glands
Thyroid Gland
Parathyroid Glands
Acknowledgment
Chapter References
This chapter provides an overview of diagnostic imaging in otolaryngology and head and
neck surgery. It presents the principles and current modalities used in regional evaluation
of the head and neck. The indications, applications, and limitations of conventional
screening methods and high-technology imaging are delineated for a variety of
otolaryngologic disorders.
PRINCIPLES OF IMAGING
A diagnostic imaging study is the most common consultation that otolaryngologists and
head and neck surgeons request for a patient. Because many of the supporting and deep
structures of the head and neck are beyond direct topographic evaluation, even with
fiberoptic endoscopes and telescopes, further anatomic and physiologic information must
be obtained for the temporal bone, skull base, paranasal sinuses, soft tissues of the neck,
larynx, and other structures by means of diagnostic imaging. This does not mean that
every patient needs an imaging study. Some patients need only a sensitive and thoughtful
examiner. Other patients need conventional plain radiographs to complete the assessment.
Others, however, need high-technology imaging for an accurate diagnosis and optimal
treatment planning.
The influence of professional development and the team approach to diagnostic imaging
is growing. Neuroradiologists have long gravitated to the field of head and neck
radiology, and interventional specialization has extended far beyond this discipline.
Angiography provides a model in which diagnostic imaging has led to interventional
imaging and the training of dedicated specialists. A radiologic examination must be
treated as a consultation to derive optimal information for formulating the best working
diagnosis. This is the essence of effective diagnostic imaging, and it is achieved through
effective communication between otolaryngologist and radiologist and through mutual
analysis of the clinical problem and radiologic evidence. Consultation involves a well-
prepared requisition, a telephone call, or a copy of the referring letter or consultation
report.
The consulting team members must establish the optimal working diagnosis. Treatments
may vary, but there is only one diagnosis, and it must be qualitatively and quantitatively
effective (Table 6.1). Qualitative aspects of diagnosis usually lie within the field of the
pathologist. However, the diagnostic image can provide qualitative answers to questions
about whether disease exists, whether there is a specific disease process, such as a
fracture, or whether a group disorder, such as bone destruction or cyst formation, can be
identified. Diagnostic images also contain answers to quantitative questions about the
extent of disease in all three dimensions, about disease that crosses regional boundaries
that affect management, and about whether the disease is a local manifestation, metastatic
condition, or systemic disorder. Imaging can help to inform the clinician about the
presence and nature of a specific anatomic or physiologic derangement.

TABLE 6.1. CLINICAL PROBLEMS DIRECTING
RADIOLOGIC CONSULTATIONS



The foregoing are the types of issues clinicians formulate for imagers and for which
solutions can be provided. However, routine questions receive only routine responses.
Fifty percent of diagnostic information can be lost from computed tomography (CT) and
magnetic resonance imaging (MRI) if the studies are not tailored to provide specific
answers to pathologic anatomic and physiologic questions.
IMAGING MODALITIES
Conventional Imaging
The modalities representative of conventional imaging are listed in Table 6.2. Regional
plain-film routines, series, or examinations are used to survey the temporal bone (Table
6.3) and to examine the paranasal sinuses (Table 6.4). A variety of radiographic signs can
be recognized from alterations in the interfaces and contrasts among bone, soft tissue, and
air in accordance with the 16 shades of gray recognized by the human eye. The
radiographic signs of paranasal sinus disease are listed in Table 6.5.

TABLE 6.2. CONVENTIONAL IMAGING



TABLE 6.3. TEMPORAL BONE PROJECTIONS



TABLE 6.4. PARANASAL SINUS AND
MAXILLOFACIAL PROJECTIONS



TABLE 6.5. RADIOLOGIC SIGNS IN PARANASAL
SINUS DISEASE



Familiarity with conventional radiographic signs and a protocol for careful examination
of radiographs based on proper clinical information leads to effective interpretation. The
conventional temporal bone examination rarely is used today. Computed tomographic
examinations are readily available and provide superior temporal bone information.
Acquisition of conventional x-ray films of the sinuses is the most common radiographic
examination performed in the practice of otolaryngology. More than half of all
conventional radiographic studies requested are of the paranasal sinuses, and these may
be augmented by other radiographs, such as those obtained in the right and left orbital
oblique projections and those of the nasal bones and zygomatic arches. Selective views,
such as a lateral radiograph of the nasopharynx for measuring the adenoids or of the
larynx and trachea for detecting a foreign body, are also commonly requested. These
regional screening examinations and selective views should be reviewed to assure
technical quality before the patient leaves the radiology department.
Some of the conventional imaging modalities listed in Table 6.2 rarely are requested
because newer forms of imaging have more to offer. However, panoramic tomography of
the teeth, mandible, and maxilla and a barium swallow examination of the hypopharynx
and esophagus frequently are requested. Modified barium swallow is an actively
monitored examination in which the radiologist's attention must be focused on clear
identification of the clinical problem to be solved.
High-technology Imaging
High-technology imaging (Table 6.6) includes CT, MRI, angiography, diagnostic
ultrasonography, radionuclide scanning, and positron emission tomography. High-
technology imaging supplements the screening information obtained with conventional
radiographic examinations. The expansion of information occurs structurally. For
example, CT expands the gray scale of conventional radiography into the thousands.
Expansion also occurs physiologically, as in low-resolution radionuclide scans. Magnetic
resonance imaging and angiography provide anatomic and physiologic information.
High-technology imaging allows intervention such as ultrasound-guided fine-needle
aspiration (FNA) biopsy or intra-arterial embolization.

TABLE 6.6. HIGH-TECHNOLOGY IMAGING
MODALITIES AND APPLICATION BY HEAD
AND NECK REGION



HEAD AND NECK RADIOLOGY BY REGION
Temporal Bone
The temporal bone is the most complex anatomic structure in the body, and pathologic
changes may induce only modest radiologic signs. The proximity of the temporal bone to
important bony structures, such as the base, vault, and foramina of the skull, leads to
summation and superimposition, which cause masking effects of fine details on
conventional images. Radiologic investigation of the temporal bone complex and related
structures may be inadequate unless high-technology imaging modalities are used (Table
6.6). Before sophisticated imaging modalities were developed, standard projections
(Table 6.3), pneumoencephalography, contrast cisternography, and, beginning in the
1950s, complex motion or pluridirectional polytomography were widely used for the
evaluation of temporal bone disease.
Conventional temporal bone projections still are used in many parts of the world where
CT and MRI are not readily available. Conventional modalities depict the key attic,
aditus, and antral region, mastoid pneumatization, and petrosa. Some pathologic
conditions, such as chronic suppurative otitis media with or without cholesteatoma, acute
coalescent mastoiditis, and large tumors of the internal auditory canal or the
cerebellopontine angle such as acoustic neuroma, meningioma, and subarachnoid cyst,
can be identified primarily from evidence of bone destruction. Pneumoencephalography
and cisternography were used mainly to depict acoustic neuroma by using contrast
medium to accentuate filling defects. Complex motion tomography supplemented these
interventional procedures. These techniques allowed multiplanar assessment of bone
destruction. However, acoustic neuroma was identified from bone destruction in only
60% of instances. A tumor had to reach a large size to produce enough bone destruction
to be radiologically recognized. Complex motion tomography allowed assessment of
congenital malformations, otosclerosis, and temporal bone fractures.
Computed tomography can be performed with high-resolution bone algorithms, and a
series of contiguous or overlapping CT sections can be processed to generate excellent
images. Spatial resolution in MRI has increased such that information offered about the
cerebellopontine angle, internal auditory canal, cochlea, and vestibule exceeds that
obtained with CT. A contrast-enhanced study is of value in many situations. Magnetic
resonance imaging and CT are not mutually exclusive examinations and are frequently
combined to fully assess lesions of the base of the skull. Angiography is reserved for the
detection of arterial stenotic lesions and arteriovenous fistulae, for the evaluation of
tumor vascularity, and for preoperative embolization.
Computed tomography and MRI have become the radiologic methods of choice for most
disorders of the ear and temporal bone. These high-technology studies also can be used to
evaluate the neighboring skull base and related structures of the middle and posterior
cranial fossae. Magnetic resonance imaging and CT are complementary. Computed
tomography is good for imaging diseases that affect cortical bone, air spaces, and some
soft tissue lesions of the temporal bone. Magnetic resonance imaging is excellent for
evaluating soft tissues, cerebrospinal fluid, and blood vessels. However, the thin cortical
bone and air-containing spaces of the middle ear and mastoid cause signal voids, which
make it difficult to differentiate air from bony septations. Therefore, high-resolution CT
is still the procedure of choice for bone assessment. Computed tomography is excellent
for evaluating congenital anomalies, including cochlear and labyrinthine anomalies, with
a special emphasis on Mondini dysplasia, congenital microtia, and other middle ear
abnormalities. The degree of otomastoid pneumatization, the status of the ossicular chain,
the course and position of the facial nerve, the positions of the internal carotid canal,
sigmoid sinus, and jugular bulb, the thickness of the atretic plate, and the dimensions of
the middle ear all are important in assessing operability. In most cases, intravenous
administration of contrast material is not needed unless the study is performed to evaluate
the central nervous system or vascular structures. The main disadvantages of CT are that
it cannot be used to image the internal auditory canal and that it has limited value in
imaging in multiple planes because many patients cannot be positioned for direct coronal
or sagittal images.
In the diagnosis of erosive disease of bone, such as chronic otitis media with
cholesteatoma, CT with bone window settings provides the best information. The
locations, extent, and nature of the complications of cholesteatoma are ideally evaluated
with CT. Acute coalescent mastoiditis, which usually occurs as masked mastoiditis, can
be identified by means of thin-section axial and coronal CT examinations. Intracranial
complications, such as sigmoid sinus thrombosis, extradural and subdural abscesses, and
brain abscess, are best detected with contrast-enhanced CT with both bone and soft-tissue
window settings. Even with MRI, dural sinus thrombosis is a difficult imaging diagnosis.
Magnetic resonance angiography and MR venography are state-of-the-art examinations
for evaluation of this dangerous clinical condition. Computed tomography allows the
relative identification and differentiation of soft-tissue abnormalities associated with
chronic ear disease, such as granulation tissue, mucopurulent effusions, cholesteatoma,
and cholesterol granuloma. High-resolution CT is an excellent and sensitive means of
imaging temporal bone fracture lines. Magnetic resonance imaging is recommended if the
presence of coexisting intracranial abnormalities is suspected. Hemotympanum, ossicular
chain disruption, and injury to the facial nerve canal are common radiologic findings.
Posttraumatic cerebrospinal fluid leak is still best depicted on intrathecally enhanced CT
scans.
Computed tomography with intravenous administration of contrast medium has been
used routinely in screening for masses in the cerebellopontine angle. Acoustic neuroma is
the most frequent tumors in this location. Computed tomography can accurately depict
lesions larger than 1 cm in diameter, but it is generally unreliable for smaller tumors.
Since the introduction of paramagnetic contrast agents, the usefulness of MRI has greatly
improved. When a retrocochlear lesion is suspected on clinical grounds, MRI with
gadolinium enhancement is the imaging modality of choice (1). It is superior to CT for
evaluating acoustic neuroma because with contrast medium it can depict tumors smaller
than 0.8 cm in diameter. Magnetic resonance imaging with gadolinium
diethylenetriamine pentaacetic acid contrast enhancement can help in the assessment of
primary soft-tissue abnormalities in the temporal area, such as facial nerve lesions,
labyrinthine schwannoma, and vestibular neuronitis. The superiority of MRI also is
recognized in the evaluation of other lesions that affect the cranial nerves and
cerebrospinal axis (2).
Other diagnostic modalities for vascular imaging of the temporal bone area include
superselective angiography and digital subtraction angiography for screening.
Angiography also can be used to direct interventional procedures. These modalities are
useful in evaluating primary vascular tumors, such as glomus jugulare tumor and its
extension beyond the jugular foramen into the skull base and temporal bone. These
studies also are important in recognizing anomalies that can lead to surgical disasters. An
aberrant middle ear internal carotid artery or high jugular bulb can be identified by means
of primary vascular screening studies, by means of reconstructive or direct CT, and by
means of MR angiography.
Combination radionuclide bone and gallium scans are essential in diagnosing malignant
external otitis (osteomyelitis of the temporal bone) and in assessing stage and response to
treatment. These scans provide physiologic information beyond the morphologic findings
on CT scans.
Paranasal Sinuses
The paranasal sinuses are air-filled cavities surrounded by bone. They are inaccessible to
direct clinical examination unless telescopic intervention is used. Cooperation between
clinician and imager is essential for effective treatment decisions and follow-up
evaluation, especially for endoscopic techniques, in which the osteomeatal complex must
be thoroughly studied with CT.
Conventional plain radiography once was the imaging modality of choice in the
evaluation of the paranasal sinuses. The clinical and radiographic emphasis was on
disease in the maxillary and frontal sinuses. Superimposition of structures precluded
accurate evaluation of the anatomic relations of the ethmoid sinuses and osteomeatal
complexes. With the recognition of the importance of the osteomeatal complex in sinus
disease and a change in therapeutic approach, CT has replaced conventional radiography
as the primary diagnostic modality.
The target structures and views for conventional plain radiographic examination of the
paranasal sinuses are summarized in Table 6.4. A complete series of sinus radiographs
usually includes Waters, Caldwell, lateral, and submentovertex views; right and left
oblique orbital views are obtained if the orbital apex or optic canal approximates the area
of concern. Additional views may be needed to study the nasal bones or zygomatic
arches. Panoramic tomography or focused dental radiographs can be used to evaluate
apical dental disease that affects the maxillary sinuses. Conventional radiographs can be
accurate in showing air-fluid levels, but the degree of chronic inflammatory disease
present is consistently and substantially underestimated (3). Unlike conventional
radiography, CT clearly depicts the fine bony anatomy of the osteomeatal complexes.
Before the introduction of CT, complex motion tomography provided critical anatomic
information, especially when bone destruction or bone displacement was in question.
Contiguous sections can be as close as 1 mm apart in coronal or lateral projections to
detail regions of interest after a preliminary screening examination has been performed
with 3- to 5-mm contiguous sections, as in assessing a blow-out fracture of the orbital
floor. This technique is used if CT is not available. Although it allows clear morphologic
visualization of bony abnormalities, the conventional technique has a limited gray scale.
Computed tomography has been advocated for improved diagnosis and is considered the
best method for evaluating the paranasal sinuses. Imaging in the coronal plane is
recommended because it optimally displays the osteomeatal units, including the relation
of the brain to the ethmoid roof and the relation of the orbit to the paranasal sinuses.
Coronal images closely correlate with the surgical approach used in endoscopic sinus
surgery. Axial images are recommended in addition to coronal images when a patient has
severe disease in the frontal, sphenoid, or posterior ethmoid sinuses, especially if surgery
in these regions is being considered. The initial CT scan should be obtained after an
adequate course of medical therapy to eliminate reversible mucosal inflammation (4).
Modern spiral CT scanners rapidly acquire thin axial images. Use of reformatted coronal
images allows examination of pediatric patients and of patients who find it difficult to
maintain the position needed for coronal imaging.
Inflammatory conditions, trauma, mucocele, and tumor are critical conditions in which
the use of CT is mandatory. Understanding orbital-sinus and cranial-sinus relations is
essential in assessing the pretreatment stage of carcinoma of the nasal cavities or
paranasal sinuses, response to radiation therapy, or postoperative tumor recurrence. Axial
examinations are essential for observing breaching of the posterior wall of the maxillary
sinus. Although CT can be performed without contrast enhancement, enhancement can
help differentiate obstructive secretions and a mass (MRI is most useful for this purpose).
Tumor extension beyond the sinuses into the orbit, brain, or retromaxillary region is best
seen with contrast enhancement.
Contrast enhancement techniques are important in evaluating vascular lesions.
Angiofibroma of the nasopharynx necessitates use of this technique to identify the
epicenter and extension of angiofibroma from the region of the sphenopalatine foramen,
medially into the nasopharynx or laterally into the infratemporal fossa and anteriorly into
the maxillary sinus or superiorly into the middle cranial fossa. Cerebrospinal fluid leak
and meningocele are two neurogenic disorders that can necessitate intrathecal CT
enhancement. Computer-generated three-dimensional CT images are being used
increasingly in evaluating complex facial fractures and severe craniofacial anomalies.
Computed tomography and MRI can be used intraoperatively during image-guided sinus
surgery. Conventional radiographs, complex motion tomography, and CT have common
radiographic signs (Table 6.5) (5).
Magnetic resonance imaging is most useful in the evaluation of regional and intracranial
complications of inflammatory sinus disease, in the assessment of benign versus
malignant sinus opacification. and in the evaluation of the extent of neoplastic processes
(6,7). Compared with CT, MRI provides better visualization of soft tissue, but it does not
optimally display the cortical air-bone interface. Therefore, CT is still a more reliable
operative road map for a surgeon performing an endoscopic procedure on the sinuses.
Staging systems are used to evaluate CT scans of the sinuses (8).
The introduction of MRI has influenced the diagnosis, management, and follow-up
evaluation of tumors of the nasal cavities, paranasal sinuses, and nasopharynx. Magnetic
resonance imaging is better than CT in the assessment or characterization of soft-tissue
mass lesions. Magnetic resonance imaging depicts vascular structures without the use of
intravenous contrast agents. Inflammatory lesions have high signal intensity on T2-
weighted images, and tumor masses tend to have low or intermediate T2-weighted signal
intensity. If MRI shows a noninflammatory mass, biopsy should be strongly considered.
Other diagnostic modalities used to study the paranasal sinuses have lesser but selective
importance. Ultrasonography of the maxillary and frontal sinuses has limited usefulness
but can help identify fluid when conventional radiographs show opacification.
Radionuclide bone scans with technetium 99m methylene diphosphonate depict
osteoblastic activity in several situations, particularly identification of focal
manifestations of systemic disease, such as Paget disease. Detection of these nonspecific
findings is highly sensitive, and the bone scan technique shows physiologic changes
before morphologic studies with conventional radiographs and CT scans do. Gallium
citrate scans, if used in combination with bone scanning, allow diagnosis of osteomyelitis
and follow-up assessment of the effectiveness of treatment. Treatment is considered
successful when results of a gallium scan return to normal. This modality specifically
images the infective focus, unlike bone scanning, which images the osteoblastic response
around the infective focus (9).
Soft Tissues of the Neck
Head and neck masses have traditionally been classified as benign or malignant, primary
or metastatic, and congenital or inflammatory. This classification is further extended to
cover age groups, such as children and adults, and location, such as midline and lateral,
anterior triangle and posterior triangle. Although the most important preliminary step in
evaluating neck masses is a careful physical examination of the neck and all mucosal
surfaces, this often only establishes a working diagnosis or defines an outstanding clinical
problem (Table 6.1). The uncertainty associated with clinical diagnosis is determined by
limitations in differentiating solid and cystic lesions and in determining anatomic
associations. Radiologic imaging is essential in responding to these clinical problems.
Conventional plain radiographs are not usually helpful in differentiating neck masses,
except for recognizing infrequent signs such as calcification. Ultrasonography is a safe,
relatively inexpensive, and readily available investigative method. Ultrasonography is
categorized as high-resolution real-time imaging or as Doppler-based technique used to
assess flow characteristics of the major blood vessels of the neck. Palpable lumps in the
neck can be assessed with ultrasonography, which can be used for specific assessment of
growth (size of lesion over time); location; relation of lesion to the adjacent structures,
especially blood vessels; character of the lesion (solid, cystic, complex); and the number
and size of affected lymph nodes in the region. Applications of ultrasonography include
assessment of thyroglossal duct abnormalities, branchial cleft cysts, cystic hygroma,
major salivary gland tumors, inflammatory processes that progress to abscess formation,
and carotid body tumors, lymph node staging, and imaging-guided FNA.
Ultrasound techniques combined with FNA and cytologic evaluation have particular
importance in the assessment of the soft tissue of the neck (10). The superiority of
ultrasonography is only in its nonradiographic guidance capability including FNA biopsy
of cervical lymph nodes or other masses. Ultrasonography also can be useful for
percutaneous drainage of cervical abscesses. Fine needle aspiration biopsy guided by
computed tomography can be used to diagnose poorly accessible or deep-seated lesions
of the head and neck (11).
Computed tomography and MRI are widely used for primary staging of tumors and
nodes. However, accuracy in assessing lymph nodes depends on the radiologic criteria
used. Various criteria for the size of lymph nodes have been used for diagnosing
metastatic lymphadenopathy, but the most reliable imaging finding is the presence of
nodal necrosis. Areas of central nodal necrosis larger than 3 mm are routinely identified
on contrast-enhanced CT scans. The usefulness of MRI and CT in the detection of lymph
node metastasis from squamous cell carcinoma of the head and neck was assessed by
Curtin et al. (12). Computed tomography performed slightly better than MRI in the
detection of lymph node metastasis. A high negative predictive value was achieved only
when a low size criterion (5 to 10 mm) was used and was therefore associated with a
relatively low positive predictive value. For example, with criteria of 1-cm size or an
internal abnormality to indicate a positive node, CT had a negative predictive value of
84% and a positive predictive value of 50%. Magnetic resonance imaging had a negative
predictive value of 79% and a positive predictive value of 52%. Ultrasonography is
hampered by similar morphologic criteria, and only ultrasound-guided FNA biopsy can
offer additional cytologic criteria that may be more reliable (13). Positron emission
tomography with 18-fluorodeoxyglucose in the detection of cervical lymph node
metastasis has been shown in several studies (14,15) to have a higher sensitivity and
specificity than CT, MRI, or ultrasound-guided FNA biopsy.
Compared with MRI, CT is the best method for studying capsular penetration and
extracapsular nodal extension. With contrast CT, extracapsular extension is identified
with an enhancing nodal rim, usually with infiltration of the adjacent fat planes. Carotid
artery invasion is an important prognostic indicator, and invasion of the adventitia is as
important as greater degrees of arterial invasion. Detection of microscopic adventitial
infiltration is beyond the scope of current imaging, but circumferential involvement of
the artery by tumor is strong evidence that the artery is invaded.
Both CT and MRI are useful to evaluate for tumor recurrence and posttreatment changes
in the care of patients with malignant tumors of the head and neck. Magnetic resonance
imaging has advantages in differentiation between tumor and scar tissue, but edema after
radiation therapy can make differentiation difficult. Radiation-induced changes lead to
false-positive diagnoses for approximately 50% of patients (16). Criteria for recurrent or
residual tumor include an infiltrative mass with high signal intensity on T2-weighted
images and enhancement after administration of gadolinium on T1-weighted images.
Computed tomographic criteria for recurrent or residual tumor include the combination of
a circumscribed, infiltrative mass with contrast enhancement on CT scans. Positron
emission tomography compares favorably with CT and MRI in the detection of recurrent
or residual cancer (17).
Other methods for detecting tumor recurrence include thallium 201 single photon
emission computed tomography (SPECT) and gallium 67 citrate whole-body
scintigraphy. Mukherji et al. (18) found thallium 201 SPECT to be superior to CT for
differentiating recurrent tumor from posttreatment changes. Murata et al. (19) found
gallium 67 citrate whole-body scintigraphy especially useful for evaluation for recurrence
and distant metastasis of squamous cell carcinoma of the head and neck.
Computed tomography is useful for detecting clinically occult primary cancer of the head
and neck that causes cervical metastasis. Magnetic resonance imaging can better depict
submucosal lesions in the areas of the tonsils, anterior floor of mouth, and base of the
tongue. Magnetic resonance imaging should be performed first for a mass in the
retropharyngeal or parapharyngeal space. In these locations, tumors of neural, vascular,
or salivary origin should be suspected. Magnetic resonance imaging also should be
performed if posterior extension into the airway, esophagus, or posterior deep muscles is
suspected. With few exceptions, CT is better than MRI in depicting thyroglossal duct
cysts, branchial cleft cysts, and cystic hygroma and in differentiating infection,
inflammatory processes such as cellulitis, edema, and abscess.
Digital subtraction angiography and conventional superselective angiography are useful
in the diagnosis of hemangioma, arteriovenous malformation, and paraganglioma. Intra-
arterial embolization has important therapeutic applications as definitive treatment or
before surgery.
Despite being hypovascular, nerve sheath tumors can become greatly enhanced on CT
scans, apparently because of extravascular leakage of contrast material into the tumor
bed. Nerve sheath tumors have intermediate signal intensity on T1-weighted images and
high signal intensity on T2-weighted images. Paraganglioma becomes intensely enhanced
after intravenous administration of contrast material during CT and MRI studies. The
characteristic salt-and-pepper appearance on MR images reflects the signal voids of many
tumor vessels. However, signal voids do not occur with all paragangliomas, especially in
those less than 2 cm in diameter.
Larynx
Radiologic imaging modalities are important in screening and in defining the deep
dimension of a malignant tumor of the larynx. Although the larynx is readily accessible
to direct visualization, including telescopic assessment, and biopsy, submucosal
extension is not subject to direct visualization. If possible, imaging studies should be
performed before biopsy to avoid confusion of tumor and local trauma. Vocal cord
mobility defects, whether due to direct infiltration by tumor or involvement of the
recurrent laryngeal nerve, can be assessed with diagnostic imaging. There also are
difficult-to-evaluate regions, such as the Morgagni ventricle or the subglottis. Imaging is
critical in the evaluation of carcinoma of the larynx in all three major regions
(supraglottis, glottis, subglottis) and in evaluation of extralaryngeal extension of
malignant growth to the hypopharynx or the laryngeal cartilage. Virtual endoscopy of the
airway is possible, but it has limited usefulness in differentiating mucosal surfaces that
are touching (20).
Conventional plain radiographs (lateral and anteroposterior projections and selective
high-kilovoltage filtration techniques) of the larynx provide preliminary or definitive
information about foreign bodies, trauma, and other types of acute and chronic airway
obstruction. These radiographs can show soft-tissue swelling, alteration of the
cartilaginous framework if sufficiently calcified, and the position of the air column. The
variability of calcification of the laryngeal cartilage can pose a diagnostic problem in the
detection of foreign bodies. For example, the superior margin of the cricoid cartilage
calcifies long before the signet portion does. The result is linear calcification on plain
radiographs that often is mistaken for a foreign body.
Xeroradiography, because it provides edge enhancement, can clarify intrinsic soft-tissue
detail such as calcification, delineate masses and stenosis, sometimes depict cartilage
abnormalities such as fractures and erosions, and help identify foreign bodies by type and
location. Unfortunately, this technique carries a radiation exposure three to five times that
of conventional radiography. The usefulness of xeroradiography in imaging of the soft
tissue and cartilage has been superseded by that of CT and MRI.
Conventional coronal tomography allows visualization of frontal view anatomy without a
superimposed spine. Thus it allows satisfactory analysis of the vertical extent of laryngeal
tumor and subglottic or tracheal stenosis or stricture. This technique has been replaced by
CT and MRI because of its limited gray scale for soft-tissue differentiation, but the
airway image, especially with the added sagittal projection, is excellent. Tomography has
several limitations, such as poor definition of the anterior commissure. Depiction of
cartilage invasion is unreliable, except when there is extensive involvement of well-
calcified cartilage.
Ultrasonography has limitations because the laryngeal cartilage reflects most of the
sound, limiting ultrasonic access. Nuclear medicine imaging seldom is useful for
laryngeal imaging. Increased uptake has been mentioned as a cause of inflammatory
arthropathy and relapsing polychondritis. Erythrocyte-tagged imaging can provide
enough information for diagnosis of the rare laryngeal cavernous hemangioma.
Arteriography is seldom used except for evaluation of a suspected vascular lesion such as
paraganglioma.
Technologic advances in CT and MRI have greatly improved the ability to image the
larynx. Spiral CT and fast MRI techniques allow rapid acquisition, which decrease
degradation motion artifacts from breathing, swallowing, and carotid artery pulsation.
Both CT and MRI allow evaluation of the extent of laryngeal tumors, especially for
tumor size staging of carcinoma. Such determinations can influence the extent of
laryngectomy (partial versus total).
Spiral CT scanners acquire the complete data set through the larynx in less than 10
seconds, allowing the patient to stay motionless. Images can then be reconstructed to give
overlapping sections, and coronal, sagittal, and even three-dimensional images can be
generated from the same data set. Examination of the larynx during various inspiratory-
expiratory cycles has been used to optimize visualization of a particular region or the
margin of a tumor. With operator-directed imaging, CT provides accurate images of the
location, size, and extent of the tumor. Computed tomography can depict cartilage
invasion and deep soft-tissue spread into the paraglottic space, preepiglottic space, and
pyriform sinuses. This T-stage imaging contributes to a more rational diagnosis and more
effective planning of surgical and radiation treatment.
The larynx has been difficult to image well with MRI because of motion artifact. Fast
spin echo imaging has made a marked difference in the ability of MRI to image the
larynx by reducing these motion artifacts. The use of gadolinium is controversial. Some
experts believe gadolinium enhancement provides important information regarding the
interface of tumor with muscle. However, fast spin echo imaging can generate similar
information, obviating administration of gadolinium. Magnetic resonance imaging is
better than CT at separating soft tissues. Another advantage of MRI over CT is
acquisition of high-resolution images in multiple planes. Sagittal images show the
epiglottis, vallecula, and base of the tongue well. Coronal views are ideal for evaluating
the margins of the vocal cords, the paraglottic space, and the vertical extent of tumor.
Axial images allow assessment of cartilaginous erosion.
The appearance of the cartilage on CT scans and MR images varies with the degree of
ossification, which is not uniform and frequently is asymmetric. Invasion of cartilage has
implications in staging and outcome of carcinoma of the larynx. With CT, tumors often
have the same attenuation as nonossified cartilage (soft-tissue density), so minimal
cartilage involvement can be difficult to assess. Gross cartilage destruction with tumor on
the opposite side of the cartilage from the primary lesion is the only truly reliable CT sign
of cartilaginous invasion. This finding is similar in MRI, but there is evidence to suggest
that lesser degrees of tumor involvement can be detected with MRI because of variability
in the appearance of both normal and abnormal cartilage afforded by MRI sequences.
Nodal staging can be dramatically improved with sensitive broadening of the primary CT
examination. Thin-section CT added to the primary tumor assessment can show enlarged
or metastatic nodes in the neck and specific anatomic and pathologic features.
Salivary Glands
The diagnosis of salivary gland disorders is established from the findings of the history,
physical examination, and FNA biopsy rather than from radiographic studies. However,
imaging studies often are needed to assess focal, multifocal, diffuse, and bilateral
disorders. New diagnoses, such as stones, can be readily established. Imaging studies can
be used to confirm a clinical suspicion, such as human immunodeficiency viruspositive
status from parotid gland enlargement with lymphoepithelial cysts.
Conventional radiographic examination that includes occlusal radiography and panoramic
tomography can depict radiopaque duct calculi. Most submandibular duct and gland
stones are radiopaque. Parotid duct stones occur infrequently and usually are radiolucent.
Conventional sialography once was the standard method of assessment of the
morphologic features of the salivary duct and glands. It is not commonly performed now,
although it provides important information about nonopaque stones, ductal stenosis,
sialectasis, and sialosis.
In imaging of the major salivary glands, ultrasonography has reasonable accuracy in
differentiating intracapsular and extracapsular lesions. It also images solid and cystic
lesions. Mixed solid-cystic lesions, such as Warthin tumor, are considered solid.
Ultrasonography is limited in depicting deep-lobe parotid lesions because of the
attenuation and reflection of sound by the mandible.
Radionuclide scanning is useful in some pathophysiologic salivary gland assessments
because
99m
Tc-pertechnetate is incorporated into the salivary glands and excreted in the
saliva. Increased focal uptake is characteristic of functioning tumors, such as Warthin
tumor of the parotid gland and the rare oncocytoma. Diffuse, increased radionuclide
uptake often indicates ductal obstruction leading to intra-acinous salivary retention in the
presence of long-standing inflammation. Positron emission tomography does not reliably
differentiate benign from malignant tumors, limiting its clinical usefulness. It also is
expensive and takes a long time to perform.
Computed tomography and MRI are excellent methods for imaging and evaluating
salivary gland disease, specifically focal, multifocal, and diffuse masses. The two
modalities have equivalent diagnostic potential for imaging solid and cystic lesions. Both
provide important information about the location (intraglandular or extraglandular), size,
and extension of tumor to surrounding superficial and deep structures.
Bone invasion is viewed differently with MRI and CT, and marrow invasion of the
mandible is better identified with MRI. The excellent soft-tissue depiction with MRI
allows identification of the intraparotid portion of the facial nerve and its relation to
infiltrative masses, which allows planning of surgical management. Magnetic resonance
imaging also is superior to CT in evaluating the muscle-tumor interface. Another
advantage of MRI over CT is the absence of exposure to radiation or the intravenous
administration of iodine-containing contrast medium.
The choice of which imaging study to perform in investigating salivary gland disease is
influenced by clinical presentation, user preference, and familiarity with a specific
modality. Computed tomography is the choice in cases of inflammatory disease of the
salivary glands, because MRI does not depict ductal dilatation or salivary calcification.
However, if the clinical finding is a mass, the initial imaging evaluation, if any, usually is
MRI. Computed tomography is an acceptable alternative, and ultrasonography can be
used as a complementary study.
Thyroid Gland
The superficial position of the thyroid gland in the neck enables easy access for clinical
examination and FNA. A wide range of high-technology imaging modalities are available
for the diagnosis and management of thyroid disease. These may generate structural
information, as do ultrasonography, CT, and MRI, or show tissue function, as does
radionuclide scanning (21).
Conventional radiography is not a primary study. It is limited to screening for airway or
esophageal displacement or invasion and to identification of calcification in the thyroid
gland. Radionuclide scanning often is chosen for imaging malignant lesions of the
thyroid. Three radioactive pharmaceuticals are commonly used in clinical practice.
Sodium
99m
Tc-pertechnetate is trapped by the thyroid gland but is not organified.
Radioiodine isotopes (iodine 123 and iodine 131) are trapped and organified by the
parenchyma of the thyroid gland. Pertechnetate is the most commonly used radioisotope,
at least for the initial evaluation. It is less expensive than radioisotopic iodine, is readily
available, and approximates iodine trapping through the metabolism of the pertechnetate
anion, which is not incorporated into hormonogenesis. Because
123
I radioiodine scanning
is unique in providing anatomic images and images of the functional activity of the
thyroid gland or ectopic thyroid tissue, it is useful in a variety of clinical situations. These
include investigation of a palpable thyroid nodule or a mass in the midline of the neck,
base of the tongue, or mediastinum. Radiopharmaceuticals can be used in the
management of cancer and Graves disease and in screening for thyroid metastasis and
postsurgical recurrent tumor.
Radionuclide scanning has several limitations. The anatomic imaging resolution is only
1.0 cm, which restricts detail and definition. Scans may not give an adequate image of
thyroid tissue if the patient is taking oral thyroid hormone supplements. A hot nodule on
a sodium
99m
Tc-pertechnetate scan may or may not indicate a functioning tumor. In these
situations, a radioactive iodine (
123
I) scan shows physiologic hormonogenesis and a
functioning or nonfunctioning mass.
High-resolution ultrasonography is the first-line structural investigative modality in the
diagnosis of many thyroid disorders, especially nodular disease. It is safe, inexpensive,
simple, quick, and reproducible. Marked improvement in image quality occurred with the
introduction of small-parts ultrasonography. Ultrasonography has an accuracy greater
than 90% in differentiating cystic and solid thyroid nodules. Mixed solid-cystic nodules
should be managed as solid masses. Ultrasonography can depict questionable or difficult-
to-palpate lesions and can be used to direct FNA. It also can show whether a palpable
nodule is part of a focal, multifocal (multinodular goiter), or diffuse process.
Ultrasonography can be used to follow the size of a nodule after suppression therapy or
cyst aspiration. The major limitation of ultrasonography is the inability to differentiate
malignant from benign lesions on the basis of tissue characteristics. This is appropriately
left to a pathologist. Retrosternal thyroid cannot be evaluated because of the bony
interference with sound.
Computed tomography and MRI have similar roles in the evaluation of thyroid disorders
and are essentially second-line imaging modalities for this region of the neck. Both
techniques provide useful information about the size, shape, and anatomic structure of
thyroid nodules. They can help determine whether a mass is solitary or part of a
multinodular lesion. Computed tomography and MRI can be used to evaluate
mediastinal, substernal, or retrosternal extension of thyroid masses and regional lymph
node involvement or local recurrence. Computed tomography shows calcification better
than does MRI, but MRI is superior in providing soft-tissue detail, especially for the
muscle-tumor interface. Magnetic resonance imaging can be performed without
intravenous contrast medium and does not expose the patient to radiation. If iodinated
contrast material is used during CT, the iodine interferes for months with thyroid function
tests and uptake of iodine 131 used postoperatively to manage well-differentiated
malignant disease of the thyroid.
Parathyroid Glands
Parathyroid imaging is controversial in terms of the indications for imaging and the
imaging agent used. Preoperative imaging localization studies are not performed at many
centers if the patient has not undergone surgical intervention (22). There are many
options for imaging the parathyroid glands, including ultrasonography, CT, MRI,
angiography and many nuclear medicine studies. Ultrasonography is the least invasive.
Because of their small size, normal parathyroid glands are not usually detected with
ultrasonography. However, parathyroid lesions larger than 0.5 cm in diameter usually can
be identified in a careful study. In cases of hyperparathyroidism due to parathyroid
adenoma, accurate localization is reported at a rate between 69% and 88% (23). Our
success rate is greater than 90%. For perithyroidal parathyroid adenoma, ultrasonography
is an excellent imaging choice, but acoustic impedance prevents adequate imaging behind
air-filled structures (trachea) or bone (mediastinum).
No nuclear medicine agent is exclusively taken up by normal or adenomatous parathyroid
glands. The agents that are taken up by both parathyroid adenoma and thyroid tissue
(thallium 201 and
99m
Tc-sestamibi) are subtracted from agents that are taken up by thyroid
tissue only (
99m
Tc-pertechnetate and iodine 123). However,
99m
Tc-sestamibi imaging is
commonly performed without subtraction because this agent washes out of the thyroid
gland rapidly but is retained by parathyroid tissue and thyroid adenoma. Although these
scans have limited value in detecting four-gland hyperplasia but have some usefulness in
detecting asymmetric hyperplasia, diagnostic accuracy is reported at between 50% and
95% in cases of parathyroid adenoma (24).
Digital subtraction angiography relies on a single morphologic characteristicthe
regional blood supply to a hypervascular gland. After the intra-arterial or intravenous
injection of contrast medium, a computerized image-subtraction program eliminates
unnecessary background information. This technique allows identification and
localization of parathyroid adenoma in 60% to 70% of patients. This modality rarely is
needed because sestamibi scans and ultrasonography are so successful. It may be useful
in revision cases of hyperparathyroidism.
Normal parathyroid glands seldom are depicted on CT scans. Markedly enlarged glands
can be detected with CT with a sensitivity of 50% to 88%. In the neck, an axial CT image
is no more informative than ultrasonography. Computed tomography is limited by
technical factors, such as inadequate resolution of lesions less than 1.0 cm in diameter, or
by limitations in interpretation, such as mistaking a tortuous vessel, thyroid mass, or
lymph node for an enlarged parathyroid gland. Use of iodinated contrast agents for
differentiating blood vessels from adenoma or lymphadenopathy prevents subsequent
imaging with iodine-based nuclear medicine studies for approximately 6 weeks.
Normal parathyroid glands usually are not identified with MRI. Magnetic resonance
imaging with gadolinium enhancement can be useful for evaluating hyperparathyroidism
refractory to the first surgical attempt at correction. T2-weighted MRI and gadolinium
fat-suppressed T1-weighted scans show parathyroid adenoma as an area of high signal
intensity against a dark, soft-tissue background. A review of the parathyroid literature up
to 1993 showed that MRI had the highest sensitivity for the detection of adenoma (74%)
followed by nuclear medicine studies (72%), CT (65%), and ultrasonography (63%) (25).
At reoperation for previously unidentified adenoma, MRI had the highest (66%).
Ultrasonography had a sensitivity of 60%; CT, 48%; and nuclear medicine studies, 45%.
ACKNOWLEDGMENT
Completion of this chapter was supported by The Saul A. Silverman Family Foundation
as a Canada-International Scientific Exchange Program (CISEPO Canada-Israel) project.

HIGHLIGHTS
Every radiologic examination is a consultation, and its value is
proportional to the communication between clinician and
radiologist.
High-technology imaging (CT, MRI, angiography,
ultrasonography, radionuclide scanning) supplements rather
than replaces conventional radiography.
Temporal bone infection and erosive disease are evaluated most
clearly with CT.
Magnetic resonance imaging is superior to CT for evaluating
acoustic neuroma.
Computed tomography is the best modality for evaluating the
paranasal sinuses.
Computed tomography is the most often used primary study for
the diagnosis of masses in the neck.
Most submandibular duct and gland stones are radiopaque;
parotid duct stones occur less frequently and are usually
radiolucent.
Technetium pertechnetate is taken up by functioning salivary
gland tumors, such as Warthin tumor and oncocytoma.
Radioiodine scanning with iodine 123 depicts the functional
activity of thyroid masses and ectopic thyroid tissue. High-
resolution ultrasonography is the first-line assessment for
determining whether a nodule is solid or cystic.
Among patients with hyperparathyroidism due to parathyroid
adenoma, the success rate of localizing the tumor with high-
resolution ultrasonography is 90%.
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4. Gwaltney JM Jr, Phillips CD, Miller RD, et al. Computed tomography study of the common cold.
N Engl J Med 1994;330:2530.
5. Noyek AM, Wortzman G, Kassel EE. Diagnostic imaging in rhinology. In: Goldman JL, ed. The
principles and practice of rhinology. New York: John Wiley and Sons, 1987.
6. Som P, Curtin H. Chronic inflammatory sinonasal diseases including fungal infections: the role of
imaging. Radiol Clin North Am 1993;31:3334.
7. Som P, Dillion W, Curtin H, et al. Hypointense paranasal sinus foci: differential diagnosis with
MR imaging and relation to CT findings. Radiology 1990;176:777781.
8. Metson R, Gliklich RE, Stankiewicz JA, et al. Comparison of sinus computed tomography staging
systems. Otolaryngol Head Neck Surg 1997;117:372379.
9. Noyek AM, Kirsch JC, Greyson ND, et al. The clinical significance of radionuclide bone and
gallium scanning in osteomyelitis of the head and neck. Laryngoscope 1989;94[Suppl 34]:1.
10. van den Brekel MWM, Castelijns JA, Reitsma CRL, et al. Outcome of observing the NO neck
using ultrasonographic-guided cytology for follow-up. Arch Otolaryngol Head Neck Surg
1999;125:153156.
11. DelGaudio JM, Dillard DG, Albritton FD, et al. Computed tomographyguided needle biopsy of
head and neck lesions. Arch Otolaryngol Head Neck Surg 2000;126:366370.
12. Curtin HD, Ishwaran H, Mancuso AA, et al. Comparison of CT and MR imaging in staging of
neck metastases. Radiology 1998;207:123130.
13. van den Brekel MW. Lymph node metastases: CT and MRI. Eur J Radiol 2000;33:230238.
14. Stokkel MP, ten Broek FW, Hordijk GJ, et al. Preoperative evaluation of patients with primary
head and neck cancer using dual-head
18
fluorodeoxyglucose positron emission tomography. Ann
Surg 2000;231:229234.
15. Nowak B, Di Martino E, Janicke S, et al. Diagnostic evaluation of malignant head and neck cancer
by F-18-FDG PET compared to CT/MRI. Nuklearmedizin 1999;38:312318.
16. Lell M, Baum U, Greess H, et al. Head and neck tumors: imaging recurrent tumor and post-
therapeutic changes with CT and MRI. Eur J Radiol 2000;33:239247.
17. Hanasono MM, Kunda LD, Segall GM, et al. Uses and limitations of FDG positron emission
tomography in patients with head and neck cancer. Laryngoscope 1999;109:880885.
18. Mukherji SK, Gapany M, Phillips D, et al. Thallium-201 single-photon emission CT versus CT for
the detection of recurrent squamous cell carcinoma of the head and neck. AJNR Am J Neuroradiol
1999;20:12151220.
19. Murata Y, Ishida R, Umehara I, et al.
67
Ga whole-body scintigraphy in the evaluation of head and
neck squamous cell carcinoma. Nucl Med Comun 1999;20:599607.
20. Gallivan RP, Nguyen TH, Armstrong WB. Head and neck computed tomography virtual
endoscopy: evaluation of a new imaging technique. Laryngoscope 1999;109:15701579.
21. Noyek AM, Finkelstein DM, Witterick IJ, et al. Diagnostic imaging of the thyroid gland. In: SA
Falk, ed. Thyroid disease: endocrinology, surgery, nuclear medicine and radiotherapy, 2nd ed.
New York: LippincottRaven, 1997:135182.
22. Miller DL. Preoperative localization and international treatment of parathyroid tumors: when and
how? World J Surg 1991;15:706715.
23. Buchwach KA, Magnum WB, Hahn FW. Preoperative localization of parathyroid adenoma.
Laryngoscope 1987;97:13.
24. Davidson J, Noyek AM, Gottesman I, et al. The parathyroid adenoma: an imaging/surgical
perspective. J Otolaryngol 1988;17:282.
25. Price DC. Radioisotopic evaluation of the thyroid and parathyroids. Radiol Clin North Am
1993;31:9911015.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

7 TRENDS IN DIAGNOSTIC PATHOLOGY
Head & Neck SurgeryOtolaryngology
7




TRENDS IN DIAGNOSTIC PATHOLOGY
ROBERT L. REDDICK
ANNE CALE JONES

R.L. Reddick: Department of Pathology, University Hospital, and Department of Pathology, The
University of Texas Health Science Center, San Antonio, Texas.
A.C. Jones: Department of Pathology, The University of Texas Health Science Center, San Antonio,
Texas.

Human Genome Project and Technological Development
p53 and Head and Neck Cancer
Microsatellite Instability and Head and Neck Cancer
Human Papillomavirus and Squamous Cell Carcinoma of the Head and Neck
Chapter References
New ideas regarding the use of diagnostic pathology in the evaluation of head and neck
cancer parallel the introduction and use of novel techniques in other areas of diagnostic
pathology. An increase in the use of molecular technology and the associated benefits
that genetic information provides about the course of disease has had a definite effect on
how pathologists and clinicians view disease. The opportunity to investigate the risk of
adverse genetic events has greatly improved as knowledge of molecular biology grows.
Traditional methods continue to be used to characterize oncologic processes. These
morphologic approaches include electron microscopy, immunohistochemistry, and
conventional histochemical staining. Although these methods provide diagnostic and
prognostic information, they are being augmented with techniques that provide
information on the genetic changes present within a tumor and the oncogenes and
antioncogenes that influence biologic behavior. Use of these novel methods has
contributed important information to the understanding of cellular differentiation and
neoplastic development. As originally anticipated, not all information gained from these
studies has been useful in defining the course of disease. Despite these limitations,
valuable diagnostic and prognostic information has been gained with molecular
technology. This information is currently being applied in protocol studies involving
therapy for various malignant tumors, such as oncogene detection to define the course of
squamous cell carcinoma of the head and neck. This chapter concerns trends in diagnostic
pathology, provides current information on the molecular biologic aspects of head and
neck cancer, and focuses on the use of molecular biologic investigations of this neoplastic
process.
HUMAN GENOME PROJECT AND TECHNOLOGICAL
DEVELOPMENT
The Human Genome Project was initiated in the 1990s to develop a comprehensive
genetic and physical map of the human genome and to elucidate the complete DNA
sequence of all human chromosomes. This project promises to provide new insight into
the diagnosis and management of malignant diseases that affect humans. A highlight of
the importance of this ambitious project is that it may become possible to obtain a genetic
profile of all humans at birth. Issues related to the ethical use of this information have to
be established, and use of this information has to be incorporated into standards of
practice. In addition to identifying genes associated with cancer and other diseases, the
Human Genome Project has led to the introduction of new terminology, contributed to
the development of new technology, and provided novel ways to study cancer and other
diseases. Genomics is the detection of genes associated with cancer and other diseases.
Proteomics was introduced as a way to describe the study of the function of individual
genes within the context of all genes in the cell at the protein level (functional genomics)
(1). The proteome is defined as the expressed protein complement of a genome (2). The
goal of proteomics is to develop a comprehensive, quantitative description of protein
expression, which may include changes that occur during the development of tumors,
dilated cardiomyopathy, or infectious disease and changes that occur after therapeutic
intervention (2). Functional genomics also includes several terms such as transcriptome
and physiome.
Laser capture microdissection was developed with the Human Genome Project (3). This
was fortuitous because laser capture microdissection provides a mechanism whereby
individual cells or groups of cells within tissues can be selectively removed and used for
genetic analysis. The development of mouse models to study the effects of gene deletions
and alterations or augmentation and the development of DNA microarray biotechnology
concomitantly increased understanding and knowledge of mutated sequences in human
tumors and their phenotypic expression. In concert with these methods or techniques,
developments in computer technology and bioinformatics have contributed to the ability
to evaluate the volume of data generated by these new technologies (4). The information
that emerges from clinical trials will determine whether these studies improve
understanding of the molecular anatomic and physiologic characteristics of normal and
neoplastic cells. For example, investigators using a lymphochip to study lymphoma
detected the complementary DNA (cDNA) arrays derived from mature lymphocytes and
their precursors with the aim of determining the phenotypic expression of DNA
alterations and the histologic type of lymphoma. With DNA microarray technology to
analyze diffuse large cell lymphoma, two diverse phenotypes were found and were
shown to have a profound influence on survival. Tumors with a profile of germinal B
cells had a better overall response to treatment than tumors in which gene expression
revealed activated B cells (5).
Information gained in the analysis of various types of tumors requires data from
numerous patients. Individual differences, tumor heterogeneity, and novel methods to
incorporate these findings into the current understanding of the multistage theory of
cancer are necessary to ascribe genetic significance to the findings about a given tumor
type. The goal of these studies is to tailor treatment to the genetic profile of a tumor.
Paramount to these studies, however, is the need for continued advances in
bioinformatics (4), the goal of which is to provide methods sufficient for data
normalization and standards to provide statistical evaluation of the myriad data derived
from these new technologies.
The use of laser capture microdissection in proteomics and genomic research has
provided a method to selectively capture for analysis individual cells or groups of cells
within tissues. In combination with DNA array technology (gene chip technology), in
which large numbers of nucleic acid samples can be assayed, new advances are being
made in the understanding of diseases that affect humans. With DNA chip technology,
cDNA clone inserts are robotically printed onto a glass slide. They are subsequently
hybridized to two different fluorescent labeled probes. The probes are pools of cDNA
generated after isolation of messenger RNA (mRNA) from cells or tissues for
comparative evaluation. The DNA probes are used to interrogate target sequences on the
basis of specificity of hybridization to the known probe. The intensity and ratio of the
fluorescent tag are measured, and the differences between the controls and the test
samples are calculated to identify genes of importance in the test samples. An advantage
of this technology is that it has produced a powerful method to evaluate the genetic
composition of tissues from archival material and to document the genetic composition of
tissues obtained from patients in clinical trials. The aim of this technology is to describe
the multitude of genes expressed in a tumor, to develop genetic profiles of cancer among
humans, and to tailor treatment to the genetic changes identified in a tumor sample.
p53 AND HEAD AND NECK CANCER
Molecular evaluation of malignant tumors that affect humans has included studies of
cellular proliferation and oncogenesis in a variety of tumors, including tumors of the
breast and prostate of adults and small blue round cell tumors of children. Most studies of
oncogenes in head and neck cancer show a limited relation between oncogene activation
and prognosis. No oncogene has achieved overall important measured against commonly
used prognostic features. In some studies, however, when detection of an oncogene was
combined with other prognostic indicators, a relation was shown between the presence of
an oncogene and development and progression of cancer.
Considerable knowledge of the genetic nature of the biologic characteristics of tumors
has emanated from studies of p53 (6). This tumor suppressor gene is located on the short
arm of chromosome 17 (17p13.1). Wild-type p53 has a role in preventing accumulation
of genomic abnormalities within cells that may lead to the development of a malignant
phenotype. Mutations in p53 have been described in a variety of tumors, and this gene is
commonly mutated in cancers that affect humans, including tumors of the head and neck
region. Cytogenetic, molecular, and immunohistochemical methods have been used to
study the role of p53 in carcinogenesis. Loss of the suppressor function of p53 most often
is caused by complete loss of one allele associated with a point mutation in the second
allele. The resultant mutated gene lacks the suppressor activity of the wild-type gene, is
metabolically stable, and has a long half-life. Under normal conditions, p53 has a short
half-life and may not be detected with current immunohistochemical methods. When p53
is mutated, altered forms can be found in 30% to 80% of tumors. The altered forms are
more stable and are therefore easy to detect with immunohistochemical methods. p53
normally prevents cells with damaged DNA from progressing through the cell cycle in
the transition from G1 into the S phase. This process allows the cell time to repair DNA
damage. The importance of a functionally intact G1 cell cycle checkpoint is emphasized
by the fact that cells lacking in wild-type p53 protein enter the S phase without having
repaired the DNA. The result is progressive genomic instability followed by initiation of
the malignant process. p53 acts as a transcription promoter and interacts with cellular
proteins such as CCAAT-binding protein and the protein product mdm2 (7). Tumors
associated with an abnormal p53 gene have been reported to be of high histologic grade
and to have increased proliferative activity. In some studies, p53 mutations have been
associated with shorter disease-free intervals and poor overall survival.
The role of p53 in the development of squamous cell carcinoma of the head and neck is
not well established (Table 7.1). Reports in the literature support a role of this tumor
suppressor gene in the evolution of cancer (8). However, in neoplasms involving the head
and neck, the relation is unclear. Hamel et al. (9) reported that patients homozygous for
the arginine allele at codon 72 of p53 had an increased risk of cervical cancer related to
infection with the human papillomavirus (HPV). Despite the recognized association
between epithelial cancer of the uterine cervix and HPV infection, no association was
found between HPV infection and squamous cell carcinoma of the head and neck in an
analysis of 163 cases. Other studies of oral squamous cell carcinoma and squamous cell
carcinoma of the head and neck had similar findings (10). Of interest is the potential
relation of cyclin D1 to the development of multiple primary neoplasms not associated
with p53, the decreased median relapse-free survival time for p53-negative tumors, and
the absence of a positive correlation between the Bcl-2 family of proteins and p53 in the
genesis of tumors of the head and neck.

TABLE 7.1. p53 EXPRESSION AND CLINICAL
CORRELATION



Gleich et al. (10) suggested that the genesis of squamous cell carcinoma of the head and
neck is most likely mediated by a variety of pathways and that single genetic alterations
are not sufficient to influence survival. Patients with tumors that have one genetic loss
had a 2-year survival rate of 78%. Patients with tumors that had two or more genetic
alterations had a median survival rate of 58%. Mutation of the p53 gene was not
associated with survival but was believed to represent a clonal marker not susceptible to
change during metastasis (11). Warnakulasuriya (12) stated that p53 mutations are not
useful in predicting outcome for patients with oral leukoplakia and are not informative as
a sole marker to predict tumor development among persons at high risk. Some studies,
however, have shown that p53 has prognostic utility in predicting the biologic behavior
of squamous cell carcinoma of the tongue. Unal et al. (13) suggested that p53 may have a
role in the biologic behavior of squamous cell carcinoma of the tongue. They reported
that p53 immunoreactivity correlates with tumor size, lymph node metastasis, and stage.
Kudo et al. (14) investigated the possible association between p53 and p21 (cyclin-
dependent kinase inhibitor) in the development of oral epithelial dysplasia and squamous
cell carcinoma. No association was found, but the authors suggested that the combination
of p21 and p53 expression may play a role in prognosis among patients with oral
dysplasia and carcinoma. Expression of p21 in oral squamous cell carcinoma may be
related to cellular proliferation and mdm2 expression that is independent of p53 protein
alterations. Lam et al. (15) found that p21 is associated with tumor stage, tumor grade,
nodal status, and mitotic count. Their findings showed that p21 is an important factor in
the progression of squamous cell carcinoma of the larynx and esophagus. Expression of
p53, p21, Rb, and mdm2 proteins in carcinoma of the tongue was investigated in a study
involving patients younger than 35 years and patients older than 75 years. The results
suggested that there are no differences in expression of these gene products in carcinoma
of the lateral aspect of the tongue (16). In laryngeal carcinoma, p27 expression was found
to be an independent prognostic indicator. In predicting the development of cancer
among patients with oral leukoplakia, several factors have been found to be associated
with the development of cancer. These include oral histologic findings, cancer history,
chromosomal polysomy, p53 protein expression, and loss of heterozygosity at
chromosomes 3p and 9p.
MICROSATELLITE INSTABILITY AND HEAD AND NECK CANCER
Little information exists about the relation between microsatellite instability and
oropharyngeal carcinoma. Lynch and Kaul (17) discussed microsatellite instability in
colorectal carcinoma in an editorial accompanying a published report that documented
the influence of microsatellite instability on the development of colorectal carcinoma. It
was suggested that the colorectal carcinomas that had microsatellite instability were more
likely to be indolent. However, the results were not statistically significant when
compared with the Dukes classification of colorectal cancer. One study (18) showed that
chromosome tetraploidization is important in malignant transformation of laryngeal
tumors. In this study, most dysplastic lesions and carcinomas in situ contained
chromosomal abnormalities. The time to development of cancer from baseline biopsy
was shorter among patients with unstable chromosomal contents than among the group
with stable chromosome contents.
Evaluation of 51 squamous cell carcinomas from various sites in the head and neck area
revealed that overexpression of p53 correlated with an increased prevalence of
chromosomal abnormalities and aneuploid tumor. A significant correlation was shown
between tumors that had metastasized and ploidy. These findings showed that tumors
with high rates of metastasis had increased chromosomal imbalances. Some studies have
shown a poor correlation between microsatellite instability and risk factors associated
with squamous cell carcinoma of the head and neck. On chromosome 9p, loss of
heterozygosity targets the same region as documented in other tumor types. The
suggestion is that the patterns of microsatellite instability documented in other types of
tumors are similar. To document the role of loss of heterozygosity, 77 oral squamous cell
carcinoma with 11 microsatellite markers located on chromosomes 3p and 9p were
studied (26). Loss of heterozygosity was identified in multiple sites, and 44% of the
tumors showed allelic loss at one or more loci on both 3p and 9p. No correlation was
shown between the frequency of loss of heterozygosity and stage of disease.
HUMAN PAPILLOMAVIRUS AND SQUAMOUS CELL CARCINOMA
OF THE HEAD AND NECK
Human papillomavirus has a role in the genesis of squamous cell carcinoma of the head
and neck (19,20). Approximately 20% of oropharyngeal tumors had the same type of or
DNA similar to the type present in squamous cell carcinoma of the uterine cervix,
perianal and anal skin, vulva, and penis. The results of these studies suggested that HPV
might have a causal relation in some types of head and neck cancer. These results also
suggested that HPV-positive tumors arising in the head and neck area have an improved
prognosis (19).

HIGHLIGHTS
Molecular biology offers an opportunity to study the role of
oncogenes in neoplastic development.
Oncogenes may play a role in the multistage process of
carcinogenesis of squamous cell carcinoma of the mouth and
elsewhere in the head and neck.
Mutations in tumor suppressor genes are associated with the
development and progression of malignant disease among
human.
The Human Genome Project allows elucidation of specific
genes and gene modifications that may influence human
development and promote neoplastic growth.
As a result of the Human Genome Project, new fields of study
have been defined, such as genomics (detection of genes
associated with cancer) and proteomics (study of genes at the
protein level).
Animal models of human disease, improvements in
bioinformatics, and enhanced computer applications in biology
provide robust tools to study human carcinogenesis.
Laser capture microdissection provides a method to selectively
remove individual cells or groups of cells from human tumors
for genetic analysis.
DNA microarray chip technology yields important information
about tumor characterization and provides a mechanism to
tailor therapy.
Microsatellite instability is used to evaluate DNA
polymorphisms in neoplastic tissues to document loss of
heterozygosity.
Microsatellite instability has provided or elucidated an
association between genetic alterations, advanced cancer stage,
and prognosis.
CHAPTER REFERENCES
1. Strausberg RL, Austin MJF. Functional genomics: technological challenges and opportunities.
Physiol Genomics 1999;1:2532.
2. Jungblut PR, Zimny-Arndt U, Zeindl-Eberhart E, et al. Proteomics in human disease: cancer, heart
and infectious diseases. Electrophoresis 1999;20:21002110.
3. Emmert-Buck MR, Bonner RF, Smith PD, et al. Laser capture microdissection. Science
1996;274:9981001.
4. Spengler SJ. Computers and biology: bioinformatics in the information age. Science
2000;287:12211223.
5. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma
identified by gene expression profiling. Nature 2000;403:503511.
6. Velculescu VE, El-Deiry WS. Biological and clinical importance of the p53 tumor suppressor
gene. Clin Chem 1996;42:858868.
7. Wu X, Bayle H, Olson D, et al. The p53-mdm-2 autoregularity feedback loop. Genes Dev
1993;7:11261132.
8. Prives C, Hall PA. The p53 pathway. J Pathol 1999;187:112126.
9. Hamel N, Black MJ, Ghadirian P, et al. No association between p53 codon 72 polymorphism and
risk of squamous cell carcinoma of the head and neck. Br J Cancer 2000;82:757759.
10. Gleich LL, Li YQ, Wang X, et al. Variable genetic alterations and survival in head and neck
cancer. Arch Otolaryngol Head Neck Surg 1999;125:949952.
11. Tjebbes GW, Leppers vd Straat FG, Tilanus G, et al. p53 tumor suppressor gene as a clonal
marker in head and neck squamous cell carcinoma: p53 mutations in primary tumor and matched
lymph node metastases. Oral Oncol 1999;35:384389.
12. Warnakulasuriya S. Lack of molecular markers to predict malignant potential of oral cancer. J
Pathol 2000;190:407409.
13. Unal OF, Ayhan A, Hosal AS. Prognostic value of p53 expression and histopathological
parameters in squamous cell carcinoma of oral tongue. J Laryngol Otol 1999;113:446450.
14. Kudo Y, Takata T, Ogawa I, et al. Expression of p53 and p21CIP1/WAF1 proteins in oral
epithelial dysplasias and squamous cell carcinoma. Oncol Rep 1999;6:539545.
15. Lam KY, Law S, Tin L, et al. The clinicopathological significance of p21 and p53 expression in
oral squamous cell carcinoma: an analysis of 153 patients. Am J Gastroenterol 1999;94:2060
2068.
16. Regezi JA, Dekker NP, McMillan A, et al. p53, p21, Rb, and MDM2 protein in tongue carcinoma
from patients <35 versus >75 years. Oral Oncol 1999;35:379383.
17. Lynch HT, Kaul K. Microsatellite instability, clinical implications, and new methodologies. J Natl
Cancer Inst 2000;92:511512.
18. Veltman JA, Bot FJ, Huynen FC, et al. Chromosome instability as an indicator of malignant
progression in laryngeal mucosa. J Clin Oncol 2000;18:16441651.
19. Gilloson ML, Koch WM, Capone RB, et al. Evidence for a causal association between human
papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 2000;92:709720.
20. Hausen HZ. Papillomaviruses causing cancer: evasion from host-cell control in early events in
carcinogenesis. J Natl Cancer Inst 2000;92:690698.
21. Agarwal S, Mathur M, Srivastava A, et al. MDM2/p53 co-expression in oral premalignant and
malignant lesions: potential prognostic implications. Oral Oncol 1999;35:209216.
22. Schoelch ML, Le QT, Silverman S Jr, et al. Apoptosis-associated proteins and the development of
oral squamous cell carcinoma. Oral Oncol 1999;35:7785.
23. Sittel C, Ruiz S, Volling P, et al. Prognostic significance of Ki-67 (MIB1), PCNA and p53 in
cancer of the oropharynx and oral cavity. Oral Oncol 1999;35:583589.
24. Charuruks N, Shin DM, Voravud N, et al. p53 expression and polysomies of chromosomes 9, 17
in head and neck cancer. J Med Assoc Thai 1999;82:466476.
25. Warnakulasuriya S, Jia C, Johnson N, et al. p53 and p-glycoprotein expression are significant
prognostic markers in advanced head and neck cancer treated with chemo/radiotherapy. J Pathol
2000;191:3338.
26. Ishwad CS, Ferrell RE, Rossie KM, et al. Loss of heterozygosity of the short arm of chromosome
3 and 9 in oral cancer. Int J Cancer 1996;69:14.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

8 ALLERGY AND IMMUNOLOGY
Head & Neck SurgeryOtolaryngology
8




ALLERGY AND IMMUNOLOGY
ROBERT M. NACLERIO

R.M. Naclerio: Department of OtolaryngologyHead and Neck Surgery, Pritzker School of Medicine,
University of Chicago, Chicago, Illinois.


Development of the Immune System
Cell-Mediated Immunity
Humoral Immunity
Immunoglobulins
Immunoglobulin G
Immunoglobulin A
Immunoglobulin M
Immunoglobulin D
Immunoglobulin E
Complement
Activation
The Classic Pathway
Alternative Pathway
Membrane Attack Complex
Phagocytic Cells
Monocytes
Granulocytes
Immune Senescence
Immunopathology
Allergy
Chapter References
Understanding immunology is fundamental to understanding the cause, diagnosis, and
management of many diseases. A basic understanding of the immune system is essential
for all physicians. Besides helping to understand disease processes, knowledge of the
immune system is essential in the evaluation of recurrent bacterial infections. Most
determinations in diagnostic immunology laboratories are based on well-established
principles of antigen-antibody reactions. This chapter is an overview of immunology and
the allergic response. The field of immunology continues to evolve rapidly, as indicated
by the identification of more than 161 cluster of differentiation surface antigens and more
than 18 interleukin molecules.
The immune system differentiates self and nonself. It identifies and destroys elements
foreign to the body and recognizes and protects self components. Immune surveillance is
the mechanism by which the immune system determines on a cellular and molecular level
how to deal with foreign invaders or with deviations of self-constituents. If the immune
system detects something foreign on a cell surface, a reaction aimed at eliminating that
cell begins. The immune system is anatomically and functionally divided into three
compartmentsprimary lymphoid organs that produce lymphocytes; lymph nodes and
the spleen, which provide a microenvironment for efficient interactions between
lymphocytes and antigens; and the extralymphoid or tertiary lymphatic tissues.
The cells primarily responsible for immune recognition are lymphocytes, which have
surface-specific receptors for antigenic determinants, or epitopes, of foreign molecules.
Because each lymphocyte bears several copies of the same receptor, the body needs
millions of lymphocytes, each with different receptors, to recognize the myriad foreign
substances that humans encounter during their lives.
The clonal selection theory of immune cell origin and development suggests that, first,
specific antigens select only the appropriate lymphocyte clone and, second, the
specificity of lymphocytes develops before the introduction of antigen. When an antigen
contacts and binds to a receptor, the lymphocyte becomes activated and then proliferates.
Proliferation or clonal expansion leads to production of a large number of lymphocytes
with the same receptors as those of the parent cell. If the body contacts the same antigen
in the future, the number of cells that can recognize it increases, and the reaction becomes
faster and more effective; that is, there is a positive immunologic memory. Sometimes
the first exposure to an antigen reduces the likelihood of a response to a second stimulus;
that is, there is negative memory or immunologic tolerance. The other transformation that
lymphocytes undergo is differentiation, by means of which they initiate protein synthesis
of lymphokines and antibodies.
The immune system has nonspecific effector mechanisms that amplify the specific
responsesthe innate immune system (1). These nonspecific features include the
response of mononuclear phagocytes, polymorphonuclear leukocytes, and the
complement system as well as enzymes, such as lysozyme, physiologic mechanisms,
such as ciliary motion, interferons, and proteins, such as acute-phase proteins.
DEVELOPMENT OF THE IMMUNE SYSTEM
The cells involved in immune reactions are derived from pluripotential hematopoietic
stem cells (2). These pluripotential stem cells arise from the bone marrow and give rise to
precursors in the erythroid, myeloid, and lymphoid lines. Molecules known as cluster of
differentiation (CD) on the surface of immune cells serve to identify subpopulations, and
they function in cell differentiation. For example, marrow hematopoietic stem cells
display CD34, whereas T cells can display CD2, CD3, CD4, CD5, CD6, CD7, CD8, or
CD28. The lymphoid precursors become either pre-B or pre-T cells.
Mature B cells have antibodies on their surface that act as antigen receptors. During early
stages of development, B cells are inactivated by contact with self components (clonal
abortion). Mature B cells, which escape clonal abortion, leave the bone marrow and
migrate to germinal centers within the lymphoid follicles of lymph nodes and the spleen.
Pre-T cells initially travel from the bone marrow to the thymus to complete their
maturation. Prethymocyte receptors are generated by random gene arrangements and
must bind to class I or class II antigens of the major histocompatibility complex (MHC)
to survive. Cells that do not recognize self (MHC) are destroyed, as are cells that bind too
tightly to the MHC (these have potential for inducing autoimmune disease). Maturation
involves interactions among T cells, thymocytes, and maturational hormones such as
thymosin, thymopoietin, and thymulin, produced by the thymic stroma. There are
positive and negative selection mechanisms for immature T cells, which maximize their
functioning. Positive selection is mediated by termination of each cell by programmed
cell death (apoptosis), which proceeds through intracellular messages. If there is little or
no binding of the T-cell receptor (TCR) to the peptide-MHC complex, apoptosis ensues,
and the cell is eliminated. The mature T cells leave the thymus and become localized in
the deep cortex of lymph nodes and in the perivascular areas of the splenic medulla. This
distribution optimizes interaction among T cells, B cells, and macrophages.
Lymphocytes (mainly T cells) recirculate between lymph nodes, blood, lymphatic
channels, and some organs, providing immune coverage of the whole body. The process
in which immune cells migrate into areas of inflammation is vital to host defense.
Coordination of the sometimes rapidly fluctuating relocation of immune cells involves a
number of molecules. For lymphocyte migration from the bloodstream, integrins
(glycoproteins) on the cell surface mediate cellular attachment to endothelium.
Inflammation incites endothelial cells to signal lymphocytes to activate their integrins by
elaborating a family of molecules called chemokines. When an immune cell surface
receptor contacts its complementary antigen, the activity of molecules involved in
adherence to endothelium greatly increases. Once the lymphocyte adheres to
endothelium, it rolls along the vessel, allowing sustained membrane contact. The
rolling feature is mediated through an interaction of selectins, which are another family of
surface glycoproteins on immune cells. After exhibiting the rolling feature, the cell
penetrates between endothelial cells. Extracellular matrix proteins (fibronectin, laminin),
intercellular adhesion molecules (ICAM-1), fibrinogen, and vascular adhesion molecules
(VCAM-1) mediate cellular movement through tissue.
The process of cellular adhesion is similar to the complement cascade, in which one
molecular interaction follows another, and the final outcome can be disrupted by the
ineffectiveness of any step. Understanding adhesion of lymphocytes and of other
circulating cells provides several approaches to inhibition of this cascade. These include
receptor-ligand binding by monoclonal antibodies, binding of small molecules to ligands,
and antisense oligonucleotides to target endothelial cell adhesion molecules and to inhibit
nuclear factor-, which regulates gene expression of several adhesion molecules, such
as ICAM-1, VCAM-1, and E-selectin. These approaches must balance the importance of
adhesion in host defense against the tissue damage induced by an overzealous response.
Persons deficient in adhesion molecules are at risk of severe bacterial infection.
CELL-MEDIATED IMMUNITY
Monocytes, macrophages, dendritic cells, Langerhans cells, and B cells can function as
antigen-presenting cells (APC), in which engulfed antigens, such as proteins, viruses, and
bacteria, are partially degraded in their phagolysosomes and presented on the cell surface
(3). Fragments of these antigens reappear later on the phagocyte surface. With its
receptor, the T cell recognizes both the presented antigen and the markers of self (MHC)
attached to the phagocyte surface. These markers of self originate in the MHC, located on
chromosome 6.
Two kinds of MHC antigens exist. Class I is composed of two polypeptide chains, one
constant from person to person and the other highly variable. Class I antigens appear on
the surface of all nucleated cells in the body and have CD8 as the TCR. Class II antigens,
composed of two variable polypeptide chains, are present on the surface of APCs and B
cells and have CD4 as the TCR. Major histocompatibility complex antigens can be
induced (class I) or repressed (class II) by the same cytokine (small proteins). This shows
that cells can have differential responses to the same immune mediator. Cytokines are
released from the APCs and alter the immune function of the presenting cell and other
cells in the immediate area. For example, interleukin-1 (IL-1), which is primarily
monocyte-macrophage derived, stimulates proliferation of B cells and some T cells,
hematopoiesis, and synthesis of tumor necrosis factor (TNF-). The redundancy of
cytokine functions combined with their proinflammatory and anti-inflammatory activities
makes it difficult to understand the role of these substances in disease.
Antigens on the surface of APCs contact helper T (T
H
) cells. The T
H
cell recognizes
foreign antigens and class II MHC antigens. To become activated, a T
H
cell needs not
only antigen and MHC binding but also IL-1, a growth factor produced by the APCs.
Costimulatory molecules binding through CD40 also play a role. The T
H
cell secretes
other growth factors, such as IL-2, which can stimulate the T
H
cells to exhibit IL-2
receptors on their surface. The up-regulation of IL-2 receptors produces an amplification
mechanism. Most immune responses require soluble growth and differentiation factors
such as IL-2. Persons deficient in these factors have severe impairment of the immune
system.
Helper T cells have been classified into subsets, T
H
1 and T
H
2, on the basis of their distinct
lymphokine secretion profile and function. The T
H
1 clones secrete IL-2, IL-3, IL-6, IL-
10, TNF-, TNF-, interferon- (IFN-), and granulocyte-macrophage colony-
stimulating factor (GM-CSF). They also proliferate in response to antigen presented by
both B cells and macrophages without a requirement for IL-1. Helper T cells in subset 1
induce IgM, IgG, and IgA but not IgE responses, and they stimulate cell-mediated
immune responses such as eradication of intracellular bacteria and viruses and delayed-
type hypersensitivity. The T
H
2 clones proliferate suboptimally in response to antigen
presented by B cells, unless IL-1 is added. The T
H
2 clones, which secrete IL-3, IL-4, IL-
5, IL-6, IL-10, IL-13, TNF-, and GM-CSF are more effective than T
H
1 clones at
assisting antibody secretion. In particular, IL-4 and IL-13 promote the switch of B cells to
IgE production. The cytokine microenvironment and the type, amount, and site of antigen
exposure affect the type of T
H
cell that develops. Helper T cells in subset 2 have been
recovered from nasal and bronchial tissues of patients with allergies after antigenic
challenge. The differentiation of T
H
0 cells to T
H
1 or T
H
2 cells may explain how different
immunization conditions can preferentially or selectively induce either humoral or cell-
mediated immune responses, and it may explain distinct patterns of disease, such as the
polar forms of lepromatous and tuberculoid leprosy. The switch from a T
H
2 cell to a T
H
1
cell response has been postulated as the mechanism underlying effective allergen
immunotherapy and the reason for the increasing prevalence of allergic rhinitis (4).
Delayed-hypersensitivity T cells (T
DH
cells) also recognize antigen. Along with class II
MHC products, T
DH
cells become activated by IL-2 and secrete lymphokines. Some of
these lymphokines activate and attract macrophages, which ingest and destroy the
antigen. This is the basis of skin testing for evaluation of delayed hypersensitivity.
Antigen, such as tuberculin, mumps vaccine, or candida, is injected intradermally. If the
antigen is recognized, local inflammation occurs, and cytokines are released that increase
expression of the adhesion molecules ICAM-1 and VCAM-1 on the vascular
endothelium. Adhesion molecules and surface molecules on T
DH
cells, such as very late
activating antigen 4 (VLA-4), interact during T-lymphocyte movement to the area. The
site becomes indurated 24 to 48 hours later. A positive response means that the patient
has adequate APCs in the skin, as well as adequate numbers of functioning T
DH
cells and
macrophages. CD8 T lymphocytes, like CD4 T lymphocytes, have been shown to have
subsets (Tc1 and Tc2). Tc1 cells secrete IFN-, and Tc2 cells secrete IL-4. The role of
these cells is just beginning to be appreciated.
Cytotoxic, or killer, T cells (T
C
cells) recognize antigen coupled to class I MHC products
(4). They kill the body's own cells that have undergone change, such as viral or malignant
transformation. For activation, T
C
cells must recognize a class I MHC plus antigen
specific for virus and then get help from T
H
cells. Once activated, the T
C
cells circulate in
the body and kill all cells that bear the new antigen through the transfer of cytolytic
compounds (perforin and granzymes). Perforins and granzymes primarily destroy some
viruses and intracellular bacteria, and they mediate rejection of grafts and tumors.
T cells can cause cell death (apoptosis) by binding to a molecule, Fas (CD 95), attached
to the surface of most cells. Binding of Fas to its ligand leads to apoptosis of the cell
expressing Fas through activation of an intracellular cascade of proteases. Fas molecules
are involved mostly in tolerance induction and regulation of T-cell maturation. Fas
expression on T and B cells increases after an encounter with an antigen. Fas ligand
begins to be expressed on mature CD4 and CD8 T cells after activation. Toward the end
of an immune response, they can induce apoptosis in cells that have up-regulated Fas.
Abnormalities in this process are responsible for a childhood disorder of
lymphoproliferation and for autoimmune thyroiditis. Fas ligand also is permanently
expressed in the eye and testis and is thought to be responsible for immune privilege at
these sites. That is, anatomic sites where transplanted foreign tissues survive for an
extended time in a person with normal immune function. How tumors provide their own
environment of immune privilege is an active area of investigation (5).
Suppressor T cells (T
S
cells) also participate in the normal regulation of immunity. Their
role in human immunology, however, has not been defined precisely. They probably
down-regulate T
H
cells and secrete suppressing lymphokines in an antigen-specific or
nonspecific manner. Evidence suggests that excess T
S
cell function occurs in some
immunodeficiency states, whereas T
S
cell deficiency occurs in some autoimmune
diseases (6).
T cells play a role in microbial immunity. Although the precise role is not defined,
these cells appear to be involved in terminating the host immune response to infection
and preventing chronic disease. After activation, T cells acquire cytotoxic activity and
kill stimulatory macrophages (7).
Unlike T
C
cells, which appear in the tissues in response to antigen, another class of killer
cells, called natural killer (NK) cells, does not depend on previous immunization. They
kill some types of tumor cells, primarily of the hematopoietic system, by means of release
of perforins and proteases and by means of induction of apoptosis. It is possible that they
regulate lymphocyte development and that their ability to kill tumors represents a cross-
reaction. In animals, tumors that are not susceptible to NK cells have greater malignant
potential than do NK-susceptible tumors. The activity of NK cells increases greatly with
exposure to interferon. These cells have an as yet undefined role in the control of viruses,
bacteria, and parasites. Natural killer cells lyse specific cells when antibody is present, a
method termed antibody-dependent cellular cytotoxicity. Natural killer cells look like
large, granular lymphocytes, but differ from mature T cells or B cells. They display CD2,
CD16, and CD56 markers, which are not classic B-cell and T-cell markers, and they do
not express surface immunoglobulins. Most can be identified by the monoclonal antibody
Leu-11. Interleukin-2 causes activation and proliferation of NK cells, now called
lymphokine-activated killer cells (LAK cells), which exhibit antitumor activity (8).
T-cell receptors for antigen are unique markers on the surfaces of T cells and are
heterodimers. Monoclonal antibodies to these surface markers can identify T cells and
their subpopulations. For example, CD3 and CD2 are antibodies that recognize all T
cells, whereas CD4 identifies helper and T
DH
cells and CD8 identifies cytotoxic and
suppressor T cells. T cells represent about 65% of lymphocytes in the peripheral blood.
Unlike B-cell receptors, which increase their affinity to antigens by means of mutation,
TCRs do not. Genetic recombinations of TCRs can produce a nearly infinite number of
antigen receptors. This is important in the distinction between self and nonself (a T-cell
function) and in prevention of autoimmunity. Once processed, antigen and associated
MHC bind TCR, and CD22 on B cells binds CD45 on T cells, which activates
intracellular phosphatyrosine phosphatase. This activates tyrosine protein kinase, which
phosphorylates components of the CD3 complex and leads to hydrolysis of membrane
phosphoinositides. The diacylglycerol and inositol 1,4,5-triphosphate produced then act
as second messengers to mobilize calcium. This activates protein kinase C, which
phosphorylates other proteins, and this causes the genetic effects that produce cell
activation and elaboration of proteins.
T-cell receptors do not bind soluble antigen as do their antibody counterparts on B cells.
Instead polypeptide antigens are internalized and processed by special APCs, which give
rise to short peptides. These bind to molecules of the MHC, and the combination is
recognized by the TCR. Superantigens, powerful microbial toxins, produced by
Staphylococcus aureus and Streptococcus pyogenes organisms cause fever and shock by
binding to class II MHC and TCR molecules. Binding to HLA-C antigen inhibits the lytic
capability of NK cells. T cells have a graded response to antigens from activation to
complete unresponsiveness.
HUMORAL IMMUNITY
Unlike T cells, B lymphocytes (B cells) have numerous receptors that bear striking
similarities to the immunoglobulin molecules they later secrete. These receptors initially
belong to the IgM and IgD classes, but later shift to IgG, IgA, or IgE. Each receptor
reacts to one antigen, so millions of B cells are needed to ensure proper immune function.
Unlike T cells, B cells do not need the joint recognition of self-markers and antigens (9).
Eighty percent to 90% of all immunoglobulin-producing cells are located in the mucosa
and exocrine glands. The adhesion molecules 47 and mucosal addressin cell adhesion
molecule 1 (MAdCAM-1) appear important in localizing B cells to these areas (10).
Some antigens can directly activate B cells (T-independent antigens), whereas other
antigens require T-cell cooperation (T-dependent antigens). In T-dependent activation,
the B cells first contact antigen through IgM and IgD molecules on the cell surface, then
process and present the antigen. The processed antigen later appears on the surface of the
B cells in association with class II MHC. An antigen-specific T cell binds to this
combination with the help of several membrane proteins (TCR, class II MHC, leukocyte
function-associated antigen 1 [LFA-1], and ICAM-1). The activated T cell then expresses
gp39, which binds to CD40, a membrane protein on B cells, and which is a potent
mitogen receptor. With the assistance of lymphokines, the B cell begins to proliferate and
differentiates into an antibody-secreting cell (plasma cell) that no longer carries
immunoglobulins on its surface. However, a percentage of B cells that have been clonally
selected remain as memory cells. These cells possess a high density of high-affinity
surface immunoglobulins, usually of the IgG, IgA, or IgE class. T-dependent activation
occurs with complex antigens, because the antigenic determinants are not accessible to
the B cell because of stereometric hindrance, forcing the antigen to be processed before
being presented.
T-independent antigens have large structures with repeating antigenic determinants
(epitopes), such as carbohydrates, which can cap and bridge immunoglobulins on the B-
cell membrane. This mode of B-cell activation is inefficient and provides primarily IgM
antibodies, because the isotype switch from IgM to IgG production in the same B cell
requires T-cell factors such as IL-4 and IFN-. Isotype switching is mediated by specific
genetic rearrangements and maintains antigenic specificity. Independent antigens include
carbohydrates from the capsule and cell wall components of bacteria. They do not include
most protein antigens. This may explain why patients with severe compromise of T-cell
function maintain antibody levels to bacterial pathogens.
IMMUNOGLOBULINS
Immunoglobulins are glycoproteins composed of 82% to 96% polypeptide and 4% to
18% carbohydrate components (2) (Fig. 8.1). They account for approximately 20% of the
total plasma proteins. All immunoglobulin molecules contain an equal number of heavy
(H) and light (L) polypeptide chains. Each polypeptide chain consists of a number of
domains of constant size (100 to 110 amino acid residues) linked by intrachain disulfide
bonds. The N-terminal domain of each chain, designated as variable region (Fab), shows
more variation in amino acid sequence than does the C-terminal end (constant region,
Fc). The antigen-binding site of the antibody molecule represents only a small number of
amino acids in the V regions of H and L chains. However, because a number of gene
segments can combine to form new V, D, and J segments, a nearly unlimited number of
antigenic specificities are possible. These amino acids are brought into close relation by
the folding of the V regions. Covalent interchain disulfide bridges hold the chains
together and form a bilateral symmetric structure. The polypeptide chains fold into
globular regions called domains. The domains in H chains are designated VH (variable
region of heavy chain) and CH1, CH2, CH3, and CH4 (constant region of heavy chain),
and those in L chains are designated VL and CL. Both ends of antibodies function in that
the Fab portion (antigen-binding fragment) binds with specific antigens, whereas the Fc
portion initiates a variety of secondary phenomena, such as complement fixation.

FIGURE 8.1. Simplified model of an immunoglobulin G
(IgG; ) human antibody molecule shows the basic four-
chain structures and domains (VH1, CH1, and so on). V,
Variable region; C, constant region. Portions of interchain
and intrachain disulfide bonds are indicated. (Adapted
from Stites PS, Terr AI, Parslow TG. Basic and disulfide
bonds: clinical immunology, 8th ed. Norwalk, CT:
Appleton & Lange, 1994, with permission.)



All of the L chains have a molecular weight of approximately 23,000 and can be
classified into two types, and , on the basis of structural differences in constant
regions. In humans, chains outnumber chains two to one. Any immunoglobulin
molecule always contains identical or chains.
Five classes of H chains exist in humans. They are based on structural differences in the
constant region. The different H chains, designated , , , , and , vary in molecular
weight from 50,000 to 70,000. The and chains possess five domains (one variable and
four constant) rather than the four domains of and chains. The H chain determines the
class of the immunoglobulin. There are five classes of immunoglobulins: IgG, IgA, IgM,
IgD, and IgE. Most of the H-chain classes have been further subdivided into subclasses
on the basis of differences in the constant regions. H chains representing the various
subclasses, however, are much more closely related to each other than to the other
immunoglobulin classes. There are four subclasses of chains in humans, 1, 2, 3, and
4, which yield IgG1, IgG2, IgG3, and IgG4 subclasses of IgG molecules. In the same
way, and chains have two subclasses each.
Immunoglobulins are present not only in serum, but also in body secretions such as
saliva, mucus, sweat, breast milk, and colostrum. Immunoglobulin A, the predominant
immunoglobulin class in external secretions, usually exists in human serum as a four-
chain unit of approximately 160,000 molecular weight. The IgA in secretions consists of
two four-chain units associated with a secretory component and a J chain. The J chain, in
contrast to the secretory component, is associated with all polymeric forms of
immunoglobulins that contain two or more basic units. The presence of a J chain
facilitates the polymerization of basic units of IgA and IgM molecules. Quantitative
measurements indicate that there is a single J chain in each IgM pentamer or polymeric
IgA molecule.
The secretory component, or polymeric immunoglobulin receptor, which mediates the
transport of polymeric IgA, is an integral membrane protein expressed in the basolateral
membrane of epithelial cells. From there, this receptor undergoes continuous endocytosis,
is transported across the epithelial cell, and then is secreted at the apical membrane into
mucosal secretions. Transport of polymeric IgA occurs after synthesis and secretion by B
cells in the lamina propria (9). Polymeric IgA binds with high affinity to the SC on the
epithelial cell and the complex is transported to mucosal secretions. Mucosal secretions
therefore contain a mixture of secretory IgA and free secretory component, except in
patients with IgA deficiency, who have only secretory component. Immunoglobulin M
also can be transported by this process. Persons deficient in IgA often have a
compensatory increase in secretory IgM.
Immunoglobulin G
In normal adults, IgG, which has the most prominent role in memory immune responses,
constitutes approximately 75% of total serum immunoglobulin. The relative
concentrations of the four subclasses are as follows: IgG1, 60% to 70%; IgG2, 14% to
20%; IgG3, 4% to 8%; and IgG4, 2% to 6%. IgG can cross the placenta and provides
protection of the newborn during the first months of life. No other immunoglobulin has
this property. Immunoglobulin G can fix complement, with the subclasses functioning
unequally: IgG3 greater than IgG1, which is greater than IgG2, which is greater than
IgG4. Immunoglobulin G4, although completely unable to fix complement by the classic
pathway, can use the alternative pathway. Other complement components adhere to the
bacterial surface and promoting phagocytosis through C3b receptors and through those
that bind IgG1, IgG3, and their Fc fragments. The coating of the bacteria with antibodies
(opsonization) makes it easier for phagocytes to capture them and increases the efficiency
of phagocytosis several hundredfold. Immunoglobulin G is involved in cytotoxicity with
NK cells. Antibody response to proteins yields primarily IgG1 and IgG3, whereas
polysaccharides elicit mainly IgG2.
Immunoglobulin A
Immunoglobulin A, most of which is produced locally, predominates in body secretions.
There are two subclasses, IgA1 and IgA2. The T
H
cells in the lymphoid tissues of the
gastrointestinal and respiratory tracts switch the B cells from IgM to IgA secretion.
Secretory IgA, because of its abundance in saliva, tears, bronchial secretions, nasal
mucosa, prostatic fluid, vaginal secretions, and mucous secretions of the small intestine,
provides the primary defense mechanism against local mucosal infection. Its main
function may be to prevent access of foreign substances to the general immunologic
system. Besides its traditional role in extracellular antibody function, IgA can neutralize
viruses intracellularly, can provide an internal mucosal barrier by intercepting antigens
and ferrying them through the epithelium, and after binding to the surface of some
leukocytes can activate the alternative pathway of complement activation.
Immunoglobulin A, however, is primarily believed to be an anti-inflammatory antibody.
Immunoglobulin A normally exists in the serum in both monomeric and polymeric forms,
constituting approximately 15% of total serum immunoglobulin.
Immunoglobulin M
Immunoglobulin M constitutes 10% of serum immunoglobulin and normally exists as a
pentamer with a molecular weight of 900,000. Immunoglobulin M antibody predominates
in the early immune response. Immunoglobulin M, with IgD, is the main
immunoglobulin expressed on the surface of B cells. It is the most efficient complement-
fixing immunoglobulin, but its huge size makes it dangerous in high concentration. The
IgM response declines and is replaced by IgG of the same antigen specificity. Fetuses
make IgM before birth, but maternal IgM does not cross the placenta. Immunoglobulin M
antibody to a specific organism in newborn serum indicates intrauterine infection.
Immunoglobulin D
Immunoglobulin D is a monomer normally present in serum in trace amounts (0.2% of
total immunoglobulin). The main function of IgD is unknown. Immunoglobulin D, with
IgM, predominates on the surface of human B lymphocytes. Its most important role may
be as a receptor.
Immunoglobulin E
Immunoglobulin E constitutes only 0.004% of total serum immunoglobulin, but it binds
with high affinity to mast cells and basophils through the Fc region. When combined with
allergens, IgE antibodies trigger the release of inflammatory mediators such as histamine
from mast cells and basophils. Immunoglobulin E also binds to macrophages, platelets,
and eosinophils by means of low-affinity receptors. Like IgD and IgG, IgE normally
exists in monomeric form.
COMPLEMENT
The complement system is the primary humoral mediator of antigen-antibody reactions
(Fig. 8.2) (11). It consists of at least 20 chemically and immunologically distinct plasma
proteins, which can interact with each other, with antibodies, and with cell membranes.
The biologic activity of complement is manifested in three ways. First, complement
proteins bind or opsonize to particles. Specific cellular receptors for these complement
proteins then mediate the binding and uptake of the opsonized particles by
polymorphonuclear leukocytes and monocytes. Second, the small fragments of
proteolytic cleavage from complement proteins diffuse readily and can bind to
neutrophils and macrophages, causing chemotaxis and cell activation. Similar receptors
on lymphocytes and APCs bind complement-opsonized antigen in the form of immune
complexes and enhance specific immune responses. At least 12 regulatory proteins and at
least five complement receptors regulate the function of complement. Third, complement
causes lysis by the insertion of a hydrophobic plug into lipid membrane bilayers and
allows osmotic disruption of the target. Deficiencies in complement frequently cause
severe infection or autoimmune disease. Most of the proteins in the complement system
are clustered on chromosome 1q and within the MHC region on 6p (12).

FIGURE 8.2. The complement system. Both pathways
generate C3 convertaseC4b2b (classical pathway) and
C3bBb (alternative pathway)which further binds C3b
to generate enzymes that activate C5 convertase. After
this, a common pathway leads to generation of the
membrane attack complex. IC, immune complexes.
(Adapted from Roitt I, Brostoff J, Male D. Immunology.
St. Louis: Mosby, 1989, with permission.)



The proteins of this system circulate as functionally inactive molecules and compose
approximately 15% of the globulin fraction of plasma. Many of these proteins are
zymogens, that is, proenzymes that need proteolytic cleavage to acquire enzymatic
activity. Each protein of the classic pathway and membrane attack complex is assigned a
number, and the proteins react in the following order: C1q, C1r, C1s, C4, C2, C3, C5, C6,
C7, C8, and C9. The proteins of the alternative pathway are assigned letters preceded by
the letter F (factor).
Activation
The most important step in differentiation of self from nonself by complement is the
covalent binding of C3 to particles. Bound C3 functions as an opsonin and as an inciter of
lytic membrane attack. Cell surfaces contain molecules that effectively limit C3
deposition, whereas nonself surfaces allow rapid deposition of many C3 molecules. The
second mechanism whereby complement differentiates self and nonself is specific
direction of C3 deposition to antigen-antibody complexes.
The Classic Pathway
The classic pathway is the main antibody-directed mechanism for the triggering of
complement activation. C1q binds to the CH2 domains of IgG in immune complexes or
to the CH3 domains of a single IgM molecule, which has been modified by antigen
binding. The next steps both amplify the response and concentrate the site of activation to
the particle that initiated activation. C1s cleaves C4 into C4a and C4b. Zymogen C2
binds to C4b and is cleaved to C2a and C2b. C4b2b, the classic pathway C3 convertase
enzyme, cleaves C3 into C3a and C3b.
Alternative Pathway
An initial requirement for activation of the alternative pathway is the presence of C3b,
which is generated continuously in small amounts. C3b reacts with factors B and D to
generate an enzyme (C3bBb) that cleaves C3 into C3a and C3b. The newly generated
C3b interacts with additional factors B and D to form more C3bBb. The C3bBb enzyme
dissociates rapidly unless it binds to properdin (P). Forming the complex C3bBbP
stabilizes it.
Membrane Attack Complex
Formation of the membrane attack complex begins with enzymatic cleavage of C5. C5
binds to C3b for cleavage by the C5 convertase enzyme (the trimolecular complex
C4b2b3b for the classic pathway and C3bBbP for the alternative pathway). Subsequent
formation of the membrane attack complex is nonenzymatic and follows successive
binding of C6 and C7 and C5b to form the C5b67 complex. C8 and C9 then bind
sequentially to this complex, resulting in formation of the lytic plug.
Breakdown products of this cascade (anaphylotoxins C3a and C5a) stimulate chemotaxis
of neutrophils and degranulation of basophils and mast cells. The anaphylotoxins have a
powerful effect on blood vessel walls, causing contraction of smooth muscle and an
increase in vascular permeability, probably mediated indirectly by release of histamine
from mast cells. Bound C3 and C4 fragments act as opsonins to enhance phagocytosis
and stimulate exocytosis from neutrophils, monocytes, and macrophages of granules that
contain powerful proteolytic enzymes and free radicals. A link between complement
activation and adaptive immunity is becoming recognized.
PHAGOCYTIC CELLS
Both polymorphonuclear leukocytes and monocytes phagocytize microorganisms during
inflammatory reactions. Although monocytes show greater diversity in function and
response, both types of cells recognize and ingest particles and soluble ligands through
receptors on their cell surfaces and digest them in their lysosomes. They also have a
number of oxygen-independent mechanisms that include lactoferrin, lysozyme, major
basic protein, and defensins. Defensins are antimicrobial cationic peptides that are
divided into and subfamilies. The defensins are produced by neutrophils; epithelial
cells produce the defensins. The defensins play a role in inflammation, wound repair,
and specific responses. They increase bacterial adherence and induce histamine release.
In contrast, defensins regulate complement and inhibit proteases (13).
Monocytes
Monocytes originate in the bone marrow from pluripotential stem cells and are released
into the blood. Tissue macrophages arise by maturation of monocytes that have migrated
from the blood. In proliferation of immature macrophages, mitogens such as colony-
stimulating factor (CSF), which is produced by fibroblasts, lymphocytes, and monocytes,
play an important role. During inflammation, both of these processes increase
dramatically. Giant cells arise either by fusion of macrophages or by failure of
cytokinesis during mitosis. The most important functional property of the macrophage is
its ability to recognize and ingest foreign and damaged materials. The capability of
macrophages to recognize opsonized particles resides in their receptors, which bind the
Fc portion of immunoglobulins and the C3 components of complement. Macrophages
possess surface MHC molecules and have receptors for activation by lymphokines and
for CSF, which regulates their function and proliferation. Monocytes also produce
complement components, prostaglandins, interferons, proteases, and cytokines.
Langerhans cells, another type of APC, are interspersed in the epithelial layer of the nasal
mucosa and skin and help to induce T-cell responses. They present antigen to T cells.
During phagocytosis, particles bound to specific or nonspecific membrane receptors are
surrounded by the cell membrane to form phagocytic vesicles. Endocytic vacuoles
become secondary lysosomes after fusion with primary lysosomes. Within the lysosomal
compartment, the contents are digested at acid pH by more than 40 hydrolytic enzymes.
After ingestion of particles, macrophages and neutrophils undergo a respiratory burst.
The burst is observed as a dramatic increase in consumption of oxygen and activation of
membrane-associated oxidase. This oxidase reduces molecular oxygen to superoxide
anion, which undergoes dismutation to hydrogen peroxide. Superoxide and hydrogen
peroxide interact to give rise to hydroxyl radicals and singlet oxygen. These reactive
metabolites of oxygen exert antimicrobial and antitumor effects.
Another group of effector molecules synthesized by macrophages includes nitric oxide
and reactive nitrogen intermediates. The macrophage itself is protected from these
oxygen metabolites by glutathione peroxidase and catalase. Many soluble agents,
including antigen-antibody complexes, C5a, ionophores, and tumor promoters, can
trigger the respiratory burst without phagocytosis.
Substances chemotactic for macrophages include C5a anaphylatoxin, bacterial products
such as N-formylmethionyl peptides, and products from stimulated B and T lymphocytes.
Also important are substances that inhibit migration away from sites of inflammation:
lymphokines (macrophage inhibitory factor and macrophage activation factor) and
proteolytic enzymes produced during activation of complement (factor Bb).
Macrophages are important in the initiation and regulation of the immune response.
Macrophages that produce IL-12 increase bronchial responsiveness associated with
eosinophil migration. Macrophages that produce IL-1 stimulate T-cell function, and they
present immune molecules to lymphocytes. This function requires display of the same
MHC determinants by both T cells and macrophages. The presence of IL-1 increases
production of prostaglandins and leukotrienes, which can alter vascular permeability and
bronchial tone. Interleukin-1 also induces production of acute-phase proteins, including
complement components, fibrinogen, and clotting factors, and increases the activity of
adhesion proteins such as ICAM-1.
Granulocytes
Polymorphonuclear leukocytes (neutrophils) accumulate at sites of acute inflammation.
This requires a series of coordinated steps that include adherence to endothelium,
extravascular migration, chemotaxis, membrane recognition and attachment to particles,
phagocytosis, fusion of lysosomes and degranulation, and a burst of oxidative
metabolism. Some of the genes responsible for the oxidative burst have been identified
and associated with chronic granulomatous disease. A genetic locus on chromosome
1q42-q44 has been identified in patients with Chdiak-Higashi syndrome, a disease
characterized by giant granules in neutrophils.
Blood neutrophils are composed of two interchangeable subpools: the circulating pool
and the marginal pool. One of the early events in acute inflammation is an increase in
neutrophil margination and adherence to the vascular endothelium. C5a, a component of
complement, mediates neutrophil chemotaxis, although other chemoattractants from
bacteria, stimulated leukocytes, products of coagulation or fibrinolysis, and oxidized
lipids exist. The chemokines plus selectins assist with neutrophil adhesion to vascular
endothelium. Neutrophils recognize particles by opsonins attached to them. These
opsonins include immunoglobulins to which the neutrophil exhibits Fc receptors and the
C3b fragment of complement. After phagocytosis, the processes described for
mononuclear phagocytex applies to the neutrophil.
Eosinophils are produced in the bone marrow, circulate in the blood, and reside
predominantly in tissues. Eosinophils have receptors for several cytokines and for IgG
and IgE. They possess several adhesion molecules (ligands), which assist in chemotaxis.
Their function is attributed to elaboration of a variety of cytokines, proteins, peroxidases,
and enzymes. One of these, major basic protein, is cytotoxic and helminthotoxic. Also
elaborated are eosinophil peroxidase, eosinophil-derived neurotoxin, Charcot-Leyden
crystal protein, and eosinophil cationic protein. Survival of eosinophils in tissues is based
on their need for several growth factors, such as IL-5, IL-3, and GM-CSF. In the absence
of growth factors, eosinophils undergo programmed cell death or apoptosis.
Basophils are granulocytes that possess high-affinity IgE receptors. They contain
histamine and other mediators, including cytokines. Basophils are believed to contribute
to anaphylaxis by releasing histamine and are known to contribute to allergic reactions at
tissue sites, such as the nose, lungs, and skin.
IMMUNE SENESCENCE
With life expectancy increasing, investigations into the effects of aging on the immune
system have increased. Results of unavoidable exposure to a large number of potential
antigens (viruses, bacteria, foods, and self-molecules) influence the immune response.
Changes reported with aging include (a) dysregulation of peripheral B and T cells with
production of large clones, (b) alterations in lymphocyte subset distribution, signaling,
and cytokine production, (c) thymic involution with a decreased output of T cells, (d) a
void of virgin T cells to respond to new infectious and noninfectious disease, (e) an
increase in the percentage of NK cells with a mature phenotype and associated
impairment of their cytotoxic capacity and their response to IL-2, (f) decreased
phagocytic capability of neutrophils, and (g) an increase in cell adhesion molecules. Low
numbers of NK cell among elderly persons is associated with mortality and the risk of
severe infection. Innate immunity, mediated by genes that remain in the germline
configuration and encode for proteins that recognize conserved structures on
microorganisms, is a much more ancient system of host defense. Innate immunity
(chemotaxis, phagocytosis, defensins, and complement) is conserved with aging (14).
IMMUNOPATHOLOGY
Immunopathology is the study of an adaptive immune response that occurs in an
exaggerated or inappropriate form and causes tissue damage. The response also has been
called hypersensitivity, and it manifests itself only after a second contact with a particular
antigen. Autoimmunity involves formation of IgG and IgM antibodies to self and reflects
a deviation from the principle of self-nonself discrimination. There are autoantibodies to
essentially every organ in the body. Several mechanisms may explain the presence of
autoantibodies. For example, a foreign antigen can cross-react with a normal body
structure, as in cross-reaction of specific streptococci and heart antigens in rheumatic
heart disease. In other cases, the release of a previously sequestered self-antigen appears,
as in postmumps orchitis. Still other cases involve a deficiency of suppressor T cells.
Autoimmune mechanisms occur in myasthenia gravis, autoimmune hemolytic anemia,
pernicious anemia, and Goodpasture syndrome.
Antibody (IgG and IgM) and antigen form soluble complexes that precipitate in basement
membranes of blood vessels with considerable outflow of plasma. These vessels include
those lining serosal surfaces, such as the peritoneum and pleura, joints, kidneys, and skin.
The complexes activate complement and set in motion an inflammatory response
characterized primarily by the influx of neutrophils. The inflammation harms the blood
vessel walls and adjacent tissues.
Delayed-type hypersensitivity is the pathologic variant of normal T-cell-mediated
immune response. Often the T-cell response to an environmental antigen can be overly
enthusiastic. Much of the damage to the lung in tuberculosis is caused not directly by
Mycobacterium tuberculosis but by the macrophages attracted by T-cell-derived
cytokines. The macrophages specialize in destroying ingested material but are not adept
at differentiating foreign antigens from host antigens. Adjacent tissues can be damaged as
innocent bystanders. Delayed-type hypersensitivity also occurs in graft rejection and
allergic contact dermatitis.
ALLERGY
Pollens and other potential allergens are deposited on the mucosal surface (Fig. 8.3).
Antigens extracted from the pollens penetrate through or between epithelial cells and
interact with APCs spread throughout the mucosa. Initial stimulation of the IgE mucosal
immune response usually occurs in the tonsils and adenoids. Chronic exposure to low
doses of antigen favors IgE over IgG production.

FIGURE 8.3. Allergy. A: Sensitization phase shows
response to allergen from unsensitized (nonallergic) state
to sensitized (allergic) state. APC, antigen-presenting
cells. B: Clinical phase shows reaction to reexposure to
allergen and subsequent phenomena leading to
inflammation. (Adapted from Stites PS, Terr AI, Parslow
TG. Basic and clinical immunology, 8th ed. Norwalk,
CT: Appleton & Lange, 1994, with permission.)



Production of IgE by B cells involves APCs and T
H
cells. Locally produced IgE first
attaches to local mast cells. Excess IgE enters the circulation and binds to receptors on
both circulating basophils and tissue-fixed mast cells throughout the body. Although the
serum half-life of IgE is only 2 days, mast cells may remain sensitized for many weeks
after passive sensitization with atopic serum containing IgE.
Persons with a family history of asthma, eczema, hay fever, and urticaria and a positive
skin test result are referred to as atopic. About 20% of the U.S. population have positive
immediate wheal and flare skin reactions to common inhalant allergens. Parents with
allergies have a higher than usual proportion of children with allergies50% of children
with two parents with allergies have an allergy. When only one parent has an allergy, the
chance is about 30%. A family history of allergy is an important risk factor for allergic
disease.
The incidence of allergic rhinitis is increasing in many industrialized nations. There is no
obvious cause of this increasing occurrence. Pollution with diesel exhaust fumes and the
prevalence of new antigens do not account entirely for this increase. The possible
reduction of infection could be shifting T-helper responses from T
H
1 to T
H
2 cells (Fig.
8.4). Immunostimulatory DNA sequences that favor a T
H
1 response have been proposed
as a means of immunotherapy to shift the allergic T
H
2 response toward a T
H
1 response.

FIGURE 8.4. Schematic shows cellular processes and
interactions after exposure to an allergen between an
antigen-presenting cell and an undifferentiated T cell.
The processes lead to cytokine release and differentiation
of T cells (top). An antigen-specific T cell interacts with a
B cell through specific ligands, receptors, and cytokines.
The result is isotype switching and secretion of IgE, with
interaction between allergen and mast cells, basophils,
and eosinophils (bottom).



The total amount of IgE alone is not predictive of an allergic state because genetic and
environmental factors, such as parasitic infestation, affect the levels. The mode of
inheritance of high levels of total IgE is not yet known, but many of the cytokines that
control its regulation map to chromosome 5. Specific antigen-specific IgE responses
frequently are associated with particular human leukocyte antigen (HLA) markers.
Mast cells are important in the allergic reaction. Mast cells are subtyped according to
content of proteases. Both subtypes contain histamine and exist in the nasal mucosa. The
final phenotype depends on local microenvironmental factors. The number of mast cells
increases in the nasal mucosa after seasonal exposure to allergens. Evidence suggests that
some microorganisms interact directly with mast cells and activate them to elicit an
inflammatory response that clears bacteriaa possible link between mast cells and innate
immunity.
Immunoglobulin E binds through its Fc receptor on the cell surface of mast cells. Cross-
linking of IgE on the surface triggers degranulation. Activation of mast cells causes an
influx of calcium ions. This process causes, first, exocytosis of granule content with the
release of preformed mediators, such as histamine, heparin, and proteolytic enzymes
(tryptase and -glucosaminidase). Second, mast cell activation induces the synthesis of
newly formed mediators from membrane-bound phospholipids. This results in production
of prostaglandins, leukotrienes, and platelet-activating factor. Cytokines such as IL-3, IL-
4, TNF
2
, and GM-CSFE also are produced by mast cells.
Minutes after antigen exposure, increases are detected in the levels of mast cell
associated mediators. Concurrent with the release of inflammatory mediators in nasal
secretions, sneezing, rhinorrhea, nasal itching, and congestion begin. Localized changes
around mast cells are amplified by neuronal reflexes. For example, stimulation of one
side of the nasal cavity with antigen causes local histamine release, which stimulates
sensory nerves. The sensory information travels to the central nervous system and
stimulates parasympathetic signals that cause bilateral nasal secretion. The nervous
system also potentially influences the reaction through release of neuropeptides.
The early response of mast cell degranulation does not entirely explain the symptoms of
patients with allergic rhinitis. The following observations support this notion: (a) The
duration of the early reaction to antigen is measured in minutes, whereas clinical disease
is more prolonged, patients reporting nasal symptoms hours after pollen exposure. (b)
Systemic glucocorticoids, although useful in refractory cases of allergic rhinitis, do not
inhibit the early reaction. (c) Biopsy of the nasal mucosa during the allergy season shows
inflammatory cellular infiltration, whereas study of the early reaction shows only mast
cell degranulation and tissue edema. (d) The dose of pollen necessary to induce
symptoms during experimental provocation exceeds severalfold the amount needed to
produce a response during the allergy season. (e) Changes in reactivity to nonspecific
irritants occur during seasonal exposure but not during the early response. Allergic
rhinitis therefore cannot be strictly considered an immediate hypersensitivity reaction.
The concept of the pathophysiologic mechanism of allergic rhinitis must be expanded.
The late response is defined as recurrence of symptoms and the appearance of mediators
in nasal secretions hours after antigen exposure. Depending on the variable analyzed, the
incidence of late reactions varies from 16% to 53% among patients with allergies with an
onset within 3 to 11 hours after antigen challenge. Among these patients, the symptoms
recur spontaneously in concordance with an increase in the levels of some but not all of
the same mediators of the early reaction.
Hours after the early response, a marked overall increase occurs in the number of cells
recovered in lavage of collected nasal secretions and in biopsy specimens obtained from
the nasal mucosa. The increase is specific for persons with allergies and is easily detected
for about two thirds of persons with allergies. The influx of eosinophils, neutrophils, and
lymphocytes is maximal 4 to 11 hours after exposure to antigen and is mediated by
adhesion molecules on the endothelium (ICAM-1, VCAM-1, selectins, and integrins) and
by their counterligands on the cells (VLA-1, LFA-1, macrophage-1 antigen [Mac-10],
and platelet-endothelial cell adhesion molecule 1 [PECAM-1]) (15) (Fig. 8.5). There
appears to be a greater eosinophil influx among persons with late reactions. The nasal
mucosa and surface secretions show similar but not identical changes. For example, the
mucosa contains greater numbers of T
H
2 lymphocytes.

FIGURE 8.5. Sequence of steps involved in lymphocyte
binding to vascular endothelium and emigration into sites
of inflammation. T-cell receptors and endothelial ligands
for each step are listed accordingly. (Modified from Rich
RR, Fleisher TA, Schwartz BD, et al., eds. Clinical
immunology: principles and practice. St. Louis: Mosby,
1996, with permission.)



In addition to their function as a barrier, cells in the epithelium are involved in the
immune process. Epithelial cells secrete IL-6, IL-8, and GM-CSF. Langerhans cells are
interdigitated with epithelial cells and present antigens to and induce activation and
differentiation of T cells. Intraepithelial lymphocytes are predominantly T cells and play
a role in the immune response. These cells secrete IL-2, IL-5, IFN-, and transforming
growth factor and have cytotoxic functions (16).
Rechallenge with allergen 11 hours after the initial provocation increases the amount of
inflammatory mediators in a pattern suggestive of both mast cell and basophil activation.
More important, the dose of antigen necessary to induce a clinical reaction is markedly
reduced. Oral glucocorticoids inhibit this increased reactivity as well as the late reaction
and the cellular influx, supporting the importance of this reaction. Repeated exposure to
antigen can maintain a constant inflammatory process in the nasal mucosa. Progressively
smaller doses of antigen induce the same allergic response (priming), explaining the
persistence of strong symptoms even beyond the peak of the pollen season. With
perennial antigens, this phenomenon can be constant, and patients have symptoms all
year.
There also is an increase in nonspecific nasal airway reactivity to histamine,
methacholine, and cold, dry air after antigen exposure. Such reactivity correlates with an
increase in the number of eosinophils and with an increase in vascular permeability in the
nasal mucosa. This increase in nonspecific nasal reactivity probably is related to the
inflammatory cellular infiltration that occurs after antigen stimulation. Topical steroids
have been shown not only to inhibit the early and late responses to antigen but also to
inhibit the nonspecific reactivity due to antigen and the accompanying eosinophil influx,
even when given after challenge.

HIGHLIGHTS
The immune system differentiates self and nonself. It identifies
and destroys elements foreign to the body while recognizing
and protecting self components. An intolerance of self leads to
autoimmune conditions.
The functions of the immune system are performed by cells
(lymphocytes, neutrophils, basophils, eosinophils, monocytes-
macrophages, mast cells) and by molecules produced by these
cells (immunoglobulins, cytokines, interleukins, interferons).
The cells primarily responsible for immune recognition are
lymphocytes, which have surface-specific receptors for
antigenic determinants of foreign molecules and for markers of
self (antigens of the MHC).
Adhesion proteins on immune cells, vascular endothelium, and
the extracellular matrix are involved in the recruitment of
immune cells to areas of inflammation.
Immunoglobulins are glycoproteins produced by plasma cells
that have multiple biologic activities, such as opsonization,
promotion of phagocytosis, antigen recognition, and
complement fixation.
Natural killer cells do not depend on previous immunization.
They kill some types of tumors, especially of the hematopoietic
system, to assist in tumor surveillance, and they eradicate
viruses.
The complement system is formed by a group of serum proteins
that can be activated by different stimuli and act as nonspecific
effectors that amplify the specific responses.
Granulocytes and monocytes recognize and ingest particles and
soluble ligands through receptors in their cell surfaces and
digest them in their lysosomes.
An allergic reaction occurs when an antigen (or allergen) comes
in contact with specific IgE attached to the surface of sensitized
mast cells. This reaction induces the release and production of
mediators responsible for symptoms in the upper and lower
airways, skin, and digestive tract.
The nasal allergic response to antigen is characterized by two
events: an early reaction minutes after contact with antigen,
with release of mast cell-derived mediators, and a late reaction,
defined as a recurrence of symptoms and the reappearance of
mediators hours after antigen exposure.
After antigen exposure, there is an increase in nasal airway
reactivity to specific and nonspecific stimuli, probably related
to inflammatory cellular infiltration.
Helper T cells in subset 2 lymphocytes and their cytokines
upregulate allergic inflammation, whereas T
H
1 lymphocytes
have the opposite effect
CHAPTER REFERENCES
1. Medzhitov R, Janeway C. Innate immune recognition: mechanisms and pathways. Immunol Rev
2000;173:8997.
2. Rich RR, Fleisher TA, Schwartz BD, et al. Clinical immunology: principles and practice. St.
Louis: Mosby, 1996.
3. Unanue BR. The concept of antigen processing and presentation. JAMA 1995;274:10711073.
4. Middleton E, Reed CE, Ellis EF, et al. Allergy: principles and practice, 5th ed. St. Louis: Mosby,
1998.
5. Chen PW, Ksander BR. Immune privilege, tumors, and the eye. Chem Immunol 1999;73:137158.
6. Delves P, Roitt I. The immune system. N Engl J Med 2000;343:3749.
7. Carding SR, Egan PJ. The importance of T cells in the resolution of pathogen-induced
inflammatory immune responses. Immunol Rev 2000;173:98108.
8. Liu C, Young LHY, Young JDE. Lymphocyte-mediated cytolysis and disease. N Engl J Med
1996;335:16511657.
9. Brandtzaeg P, Farstad IN, Johansen FE, et al. The B-cell system of human mucosae and exocrine
glands. Immunol Rev 1999;171:4587.
10. Salmi M, Jalkanen S. How do lymphocytes know where to go: current concepts and enigmas of
lymphocyte homing. Adv Immunol 1997;64:139216.
11. Douglas GN. Complement system, 3rd ed. La Jolla, CA: Calbiochem, 1989.
12. Yu C Yung. Molecular genetics of the human MHC complement gene cluster. Exp Clin
Immunogenet 1998;15:213230.
13. van Wetering S, Sterk PJ, Rabe KF, et al. Defensins: key players or bystander sin infection, injury,
and repair in the lung? J Allergy Clin Immunol 1999;104:11311138.
14. Franceschi C, Bonafe M, Valensin S. Human immunosenescence: the prevailing of innate
immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine
2000;18:17171720.
15. Nickel R, Beck LA, Stellato C, et al. Chemokines and allergic disease. J Allergy Clin Immunol
1999;104:723742.
16. Christodoulopoulos P, Cameron L, Durham S, et al. Molecular pathology of allergic disease. J
Allergy Clin Immunol 2000;105:211223.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

9 NEUROLOGY
Head & Neck SurgeryOtolaryngology
9




NEUROLOGY
FRANK E. LUCENTE
SAMIR SHAH
ROGER KULA

F.E. Lucente: Department of Otolaryngology, Long Island College Hospital, Brooklyn, New York.
S. Shah: Department of Otolaryngology, State University of New York, Health Science Center at
Brooklyn, Brooklyn, New York.
R. Kula: Department of Neurology, Long Island College Hospital, Brooklyn, New York.


Neuromuscular Disorders
Multiple Sclerosis
Myasthenia Gravis
Amyotrophic Lateral Sclerosis
Syringobulbia
Poliomyelitis
Guillain-Barr Syndrome
Tetanus
Dystonia
Palatal Myoclonus
Cerebrovascular Accident
Hemorrhage
Embolism
Subarachnoid Hemorrhage
Transient Ischemic Attacks
Posterior Inferior Cerebellar Artery Thrombosis
Basilar Artery Insufficiency
Thrombosis of the Anterior Spinal Artery
Anterior Inferior Cerebellar Artery Thrombosis
Superior Cerebellar Artery Thrombosis
Thrombosis of the Vertebral Artery
Cestan-Chenais Syndrome
Babinski-Nageotte Syndrome
Basilar Artery Thrombosis
Thrombosis of the Medial Pontine Branches
Thrombosis of Lateral Pontine Branches
Thrombosis of the Upper Pontine Branches
Thrombosis of the Internal Auditory Artery
Jackson Vagus-Accessory-Hypoglossal Paralysis
Vagus-Accessory Syndrome
Vernet Syndrome
Collet-Sicard Syndrome
Garel-Gignoix Syndrome
Tumor
Glioma
Meningioma
Kennedy Syndrome
Acoustic Neuroma
Nasopharyngeal Carcinoma
Epidermoid Tumor
Metastatic Tumor
Tumor of the Glomus Jugulare
Pituitary Adenoma
Facial Pain
Other Facial Syndromes
Complications of Ear and Sinus Infection
Osteomyelitis
Subdural Empyema
Meningitis
Brain Abscess
Orbital Cellulitis
Superior Orbital Fissure Syndrome
Cavernous Sinus Thrombosis
Chapter References
The diagnosis and management of the numerous and complex neurologic conditions that
present in the head and neck are predicated on an understanding of the neuroanatomic
and neurophysiologic characteristics of this region (1,2,3 and 4) (Fig. 9.1, Fig. 9.2, Fig.
9.3, Fig. 9.4, Fig. 9.5, Fig. 9.6 and Fig. 9.7), particularly of the cranial nerves (Table 9.1).
Many neurologic diseases have manifestations in the head and neck. In diseases such as
cerebrovascular accidents and tumors, the location of the lesion determines the
manifestations of the disorder. Demyelinating or degenerative diseases also manifest ear,
nose, and throat symptoms.

FIGURE 9.1. A: Trigeminal nerve. B: Maxillary and
mandibular branches of the trigeminal nerve. ASA,
Anterior superior alveolar nerve; At, auricular temporal
nerve; B, buccal nerve; Bu, buccinator muscle; Ct, chorda
tympani; F, frontal nerve; IA, inferior alveolar nerve; IO,
infraorbital nerve; IP, inferior palpebral nerve; L, lingual
nerve; Ln, lacrimal nerve; LG, lacrimal gland; LP, lateral
pterygoid muscle; M, masseter muscle; Mn, mental nerve;
MP, medial pterygoid muscle; NC, nasociliary nerve; PPG, pterygopalatine ganglion;
PSA, posterior superior alveolar nerve; SO, supraorbital nerve; ST, supratrochlear nerve;
TP, tensor palatine muscle.



FIGURE 9.2. Facial nerve. (Modified from The cranial
nerves. In: Anderson JE, ed. Grant's atlas of anatomy.
Baltimore: Williams & Wilkins, 1983:81, with
permission.)



FIGURE 9.3. Glossopharyngeal nerve. LP, Lesser
petrosal; ET, eustachian tube; VII, facial nerve; Sp,
stylopharyngeus muscle.



FIGURE 9.4. Vagus nerve.



FIGURE 9.5. Spinal accessory nerve. SM, Sternomastoid
muscle; T, trapezius muscle.



FIGURE 9.6. Hypoglossal nerve (cranial nerve XII).
OH, Omohyoid muscle; AH, ansa hypoglossi; St,
sternothyroid; SH, sternohyoid; TH, thyrohyoid; Gg,
genioglossus muscle.



FIGURE 9.7. Cranial autonomic ganglia. The
parasympathetic nervous system is of craniosacral origin.
Preganglionic cell bodies are associated with cranial
nerves III (ciliary), VII (pterygopalatine, submandibular),
IX (otic), and X and with spinal nerves 2, 3, and 4.
Parasympathetic ganglia are close to the structure being
innervated. The cervical portion of the sympathetic chain
forms three cervical ganglia connected by intervening
sympathetic fibers. The preganglionic fibers come from the upper five thoracic segments
of the spinal cord. The superior cervical ganglion communicates with cranial nerves IX,
X, and XII and supplies the pharyngeal plexus, carotid sinus, and carotid body. The
middle cervical ganglion communicates with cervical nerves 5 and 6 but often is small or
absent. The inferior cervical ganglion usually is fused with the first thoracic ganglion to
form the stellate ganglion, which communicates with cervical nerves 6, 7, and 8 and the
first thoracic nerve to provide sympathetic input to the upper limb.



TABLE 9.1. CRANIAL NERVES AND THEIR
FUNCTIONS AND PATHWAYS



NEUROMUSCULAR DISORDERS
Multiple Sclerosis
Multiple sclerosis is an inflammatory disease involving areas of demyelinization in the
central nervous system. This disease primarily affects young adults and is characterized
by exacerbations and remissions. The geographic distribution is distinct: the incidence is
higher in the higher latitudes and almost nil at the equator. Vertigo is the presenting
problem among 7% to 10% of patients and may eventually occur among as many as 30%
of patients. Nystagmus occurs among 70% of patients. This is usually horizontal
nystagmus, although 33% of patients with nystagmus have vertical nystagmus. Diplopia
often is caused by involvement of extraocular muscles from lesions in the medial
longitudinal fasciculus, which links the nuclei of cranial nerves VI and III and subserves
conjugate lateral gaze. Bilateral internuclear ophthalmoplegia due to a lesion of the
medial longitudinal fasciculus strongly indicates the existence of multiple sclerosis.
Deafness is rare in multiple sclerosis. The Charcot triad in multiple sclerosis consists of
nystagmus, scanning speech, and intention tremor (5). Multiple sclerosis can be
diagnosed reliably with appropriate diagnostic studies. The following findings establish
the diagnosis: magnetic resonance images that show small, demyelinated foci in the white
matter; abnormal brainstem auditory or visual evoked responses, and elevated protein
level in the cerebrospinal fluid with the presence of oligoclonal immunoglobulin banding.
Myasthenia Gravis
Myasthenia gravis is caused by impaired transmission across the myoneural junction due
to the presence of antibodies to the acetylcholine receptor. Onset occurs at all ages with
clustering among young women and older men. This disease is characterized by
weakness and abnormal fatigue of striated muscles. Remission and exacerbation are
characteristic. Ocular muscles are involved in more than 90% of these patients. There
often is weakness of facial, laryngeal, and pharyngeal muscles. The cricopharyngeal
muscle often is involved. The weakness is greater after exercise or at the end of the day.
Nystagmus and vertigo are rare. Transient neonatal myasthenia gravis occurs among one
in seven newborns born to a mother with myasthenia gravis. The infants are unable to
suck and swallow. Diagnosis is made from the history and the findings of relief of
weakness after administration of neostigmine (6). Myasthenia gravis is associated with
thymoma among 10% of patients. The disease is autoimmune in nature and mediated by
circulating immunoglobulin G antibodies to the acetylcholine receptor. A positive result
for the presence of antiacetylcholine receptor antibody (present in approximately 85% of
patients), a positive result of an edrophonium test, and abnormal results of repetitive
stimulation electromyography are highly reliable in establishing the diagnosis.
Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis is a degenerative disease of the upper and lower motor
neurons of the central nervous system. The disease is characterized by progressive
muscular weakness and atrophy along with spasticity. The otolaryngologic manifestations
are dysphagia, fasciculation, atrophy of the tongue, dysarthria, and pseudobulbar palsy.
Deep tendon reflexes are hyperactive. This disease usually occurs among middle-aged
and older persons, mainly men (7).
Syringobulbia
Syringobulbia is a progressive, degenerative disease that involves cavitation of central
parts of the cervical spinal cord (syringomyelia). It extends superiorly into the medulla
oblongata and pons and into the area of the descending tract of the trigeminal nerve or
other nuclei of bulbar structures. Signs are analgesia and thermoanesthesia of the face,
atrophy and weakness of the tongue, palatal paralysis, and vocal cord paralysis. There is
usually shoulder and upper extremity involvement (6). Arnold-Chiari type I malformation
is frequently associated. This malformation by itself even without syrinx formation can
cause Menire-like auditory and vestibular symptoms (8).
Poliomyelitis
Poliomyelitis is a viral illness usually affecting children. It has been almost eliminated in
the United States through vaccination. When poliomyelitis does occur, there usually are
several cases in a community. The onset of disease is acute and is characterized by fever,
muscle weakness, tight neck muscles, decreased deep tendon reflexes, and dysphagia (7).
Examination of the cerebrospinal fluid shows acute meningitis.
Guillain-Barr Syndrome
In Guillain-Barr syndrome, an acute postinfectious inflammatory polyneuropathy, the
patient has ascending limb weakness and muscle tenderness that in rare instances
progresses to dysphagia, respiratory failure, and minimal sensory symptoms. The patient
continues to have a fever. Guillain-Barr syndrome usually follows a viral illness or
inoculation with vaccine. The Miller-Fisher variant of Guillain-Barr syndrome begins
with weakness of facial and neck muscles before limb weakness develops (9). The
diagnosis usually is confirmed when there is an elevated level of protein in the
cerebrospinal fluid without a cellular response.
Tetanus
Tetanus is caused by a toxin produced by clostridia, usually from infection of puncture
wounds or pressure ulcers. The disease is characterized by trismus, rigid abdominal
muscles, dysphagia, and perspiration. External stimuli may trigger muscle spasms and
even convulsions. Laryngeal spasm may occur. Tetanus can be confined to the head and
neck. There usually is a history of injury, but often the trauma was trivial or not reported
(10). Tetanus often occurs among elderly persons who have not maintained their
immunizations.
Dystonia
Dystonia of the tongue or lips and facial grimacing may be caused by extrapyramidal
disease or drug intoxication. Torsion spasm involves excess muscle tone in large muscle
groups. This may involve the entire body. Movements are slow, undulant, writhing, and
twisting. This disorder may involve only the face, tongue, head, and neck, leading to
dysarthria, facial grimacing, and torticollis. Meige syndrome, known as cranial dystonia,
presents with focal or segmental dystonia involving the cranial muscles. The most
common example is blepharospasm (11). Dystonia musculorum deformans is a rare,
progressive, familial disorder manifesting dystonia. Tardive dyskinesia is a dystonia of
the lips, tongue, and facial muscles. This is a late side effect of phenothiazines that can
occur even after discontinuation of the drug. Spasmodic torticollis involves dystonic
movement of the head, neck, and shoulders. Initially, this is intermittent, but it can later
develop into persistent muscle contraction with deviation of the head. This condition can
be congenital or acquired. Some cases may be psychogenic (6). Spastic dysphonia is
considered to be a focal dystonia of the larynx.
Palatal Myoclonus
Palatal myoclonus involves involuntary movement of the pharynx and soft palate. This
movement can be suppressed by voluntary effort. Palatal myoclonus is caused by lesions
of the olivodentatorubromesencephalic pathway (6).
CEREBROVASCULAR ACCIDENT
Cerebrovascular accidents (CVAs) can be caused by hemorrhage, thrombosis, or emboli.
Hemorrhage
Hemorrhage tends to occur suddenly and during activity, especially among persons with
hypertension. Hemorrhage is the most common form of CVA in middle age. Thrombosis
is the most common form of CVA. It tends to occur among older patients, often during
rest. Thrombosis may be preceded by transient neurologic involvement referred to as
transient ischemic attacks. Thrombosis often begins with an intermittent or gradual
course. Dural sinus thrombosis occurs most commonly in childhood (3 to 5 years). The
longitudinal and straight sinuses are most frequently involved. Among adults, thrombosis
often complicates a debilitating disease, hydration, or prolonged labor and delivery. Dural
sinus thrombosis may be associated with infection of the ears and paranasal sinuses.
Signs of dural sinus thrombosis are edema of the forehead, distention of scalp veins,
lower limb spasticity, seizures, and hemiplegia. Persistent convulsions and sudden loss of
consciousness are common.
Embolism
Embolism often is sudden in onset, accounts for about one third of CVAs, and is the most
likely form of CVA to resolve. Among 10% of patients who have strokes, atheromatous
plaques are found in the proximal arterial system (carotid or vertebral basilar arteries).
Atrial fibrillation or flutter and paradoxical emboli are recognized cardiovascular
contributing factors. Embolism among younger patients often is associated with valvulitis
or acute infection of the throat or teeth. The history includes fever, malaise, weight loss,
and joint pain. There often is a sudden onset of lethargy or coma and a cardiac murmur.
Petechiae and hematuria may exist.
Subarachnoid Hemorrhage
Subarachnoid hemorrhage usually is caused by rupture of an aneurysm. This is the most
common form of CVA among patients between the ages of 17 and 35 years. Signs of
subarachnoid hemorrhage are rigidity of the neck, severe nuchal pain, and impairment of
consciousness.
Transient Ischemic Attacks
Narrowing of the internal carotid artery or middle cerebral artery can be associated with
contralateral transient muscle weakness or sensory disturbances referred to as transient
ischemic attacks. If the left or dominant hemisphere is involved, there may be a speech
disturbance. Intermittent blindness can occur in the ipsilateral eye (amaurosis fugax). If
the internal carotid artery is involved, a bruit may be heard in the neck.
Posterior Inferior Cerebellar Artery Thrombosis
Posterior inferior cerebellar artery thrombosis (Wallenberg syndrome) is characterized by
vertigo, dysphagia, ipsilateral facial paresthesia and hypesthesia, ipsilateral Horner
syndrome, and ipsilateral incoordination. There may be hypalgesia of the contralateral
trunk and limbs along with ipsilateral hypesthesia.
Basilar Artery Insufficiency
Basilar artery insufficiency is associated with recurrent vertigo, transient decrease in
vision, dysphagia, dysarthria, and diplopia. There may be hemiparesis, which may shift
from side to side. The patient may have episodes of confusion or loss of consciousness.
Thrombosis of the Anterior Spinal Artery
Thrombosis of the anterior spinal artery affects the pyramids and emerging hypoglossal
fibers. It is associated with hemianesthetic hemiplegia or with hypoglossal hemiplegia.
There is a contralateral loss of proprioception and a decrease in tactile sensation. This
may spare the hypoglossal nerve. Another result of anterior spinal artery thrombosis is
hemiplegia cruciata, a lesion of the decussation of the pyramid. The patient has
contralateral and ipsilateral spastic paresis of the lower extremities, may have ipsilateral
flaccid paresis and atrophy of the sternocleidomastoid and trapezius muscles, and may
have ipsilateral paresis of the tongue.
Anterior Inferior Cerebellar Artery Thrombosis
Anterior inferior cerebellar artery thrombosis involves the tegmentum of the upper
medulla, lower pons, restiform body, the lower part of the cerebellar peduncle, and the
inferior surface of the cerebellar peduncle. The deficits include ipsilateral loss of facial
pain, light touch and temperature sensations, ipsilateral Horner syndrome, ipsilateral
deafness, vertigo, and ipsilateral facial palsy. The patient has ipsilateral cerebellar ataxia
and a contralateral decrease in pain and temperature sensation in the limbs and trunk.
This lesion may follow excision of acoustic neuroma.
Superior Cerebellar Artery Thrombosis
Superior cerebellar artery thrombosis causes choreiform or choreoathetoid involuntary
movement and contralateral loss of pain and temperature sensation in the face and body.
The patient has ipsilateral cerebellar ataxia with hypotonia, nausea and vomiting, and
slurred speech. There may be a central facial palsy, ipsilateral Horner syndrome, and
partial deafness. This lesion involves the lateral tegmentum of the pons and midbrain,
superior cerebellar peduncle, superior surface of the cerebellum, and cerebellar peduncle.
Thrombosis of the Vertebral Artery
Thrombosis of the vertebral artery (Avellis syndrome) involves the spinothalamic tract,
nucleus ambiguus, and usually the bulbar nucleus of the accessory nerve. The patient has
ipsilateral paralysis of the soft palate and larynx, ipsilateral anesthesia of the pharynx and
larynx, and ipsilateral loss of taste. There is contralateral loss of pain and temperature
sensation in the trunk and extremities. Ipsilateral Horner syndrome occasionally results.
Cestan-Chenais Syndrome
Cestan-Chenais syndrome is occlusion of the vertebral artery inferior to the origin of the
posteroinferior cerebellar artery. This lesion involves the nucleus ambiguus, restiform
body, and descending sympathetic pathways. The syndrome is characterized by paralysis
of the soft palate, pharynx, and larynx, Horner syndrome, and ipsilateral cerebellar ataxia,
contralateral hemiplegia, and decreased proprioception and tactile sensation. Possible
involvement of cranial nerves XI and XII may cause ipsilateral paralysis of the
sternocleidomastoid and trapezius muscles and the tongue. The descending tract of the
trigeminal nerve may be involved. The result is ipsilateral loss of temperature and pain
sensation in the face.
Babinski-Nageotte Syndrome
Babinski-Nageotte syndrome involves scattered lesions in the distribution of the vertebral
artery. This causes ipsilateral paralysis of the soft palate, larynx, pharynx, and tongue,
ipsilateral decrease in taste sensation on the posterior third of the tongue, diminished pain
and temperature sensation on the face, and Horner syndrome. There is a contralateral
spastic hemiplegia and loss of proprioception and touch. There may be decreased pain
and temperature sensation in the trunk and limbs.
Basilar Artery Thrombosis
Basilar artery thrombosis causes a disorder in superficial and deep sensation in the
extremities, trunk, and sometimes the face. The pupils usually are miotic. The patient
usually has decerebrate rigidity, profound coma, and respiratory and circulatory
difficulties. This can affect bilateral cranial nerves and long tracts. There is bilateral
supranuclear fiber involvement to the bulbar nuclei.
Thrombosis of the Medial Pontine Branches
Thrombosis of the medial pontine branches involves the nuclei of cranial nerves VI and
VII, the medial longitudinal fasciculus, medial lemniscus, and pyramidal tract. The
patient has ipsilateral facial paralysis and paralysis of the lateral rectus muscle or of
lateral conjugate gaze. There is a contralateral lateral hemiplegia, loss of proprioception,
and decrease in sensation of light touch.
Thrombosis of Lateral Pontine Branches
Thrombosis of lateral pontine branches involves the middle cerebellar peduncle, the
superior olivary body, the facial nucleus, the vestibular and cochlear nuclei, and a portion
of the motor and sensory nuclei of the trigeminal nerve. The deficit involves ipsilateral
cranial nerves V, VII, and VIII and ipsilateral cerebellar ataxia. The patient frequently
has contralateral diminution of pain, temperature, proprioception, and tactile sensation on
the trunk and limbs.
Thrombosis of the Upper Pontine Branches
Thrombosis of the upper pontine branches of the basilar artery affects the pyramidal tract,
medial lemniscus, spinothalamic tract, and the ventral and dorsal secondary ascending
tract of the trigeminal nerve. This causes contralateral hemiplegia that includes the face
and tongue. There is also a loss of proprioception, pain, and temperature sensation of the
face, extremities, and trunk.
Thrombosis of the Internal Auditory Artery
Thrombosis of the internal auditory artery causes ipsilateral deafness and loss of
vestibular function.
Jackson Vagus-Accessory-Hypoglossal Paralysis
Jackson vagus-accessory-hypoglossal paralysis is a nuclear or radicular lesion of cranial
nerves X, XI, and XII. The patient has ipsilateral flaccid paralysis of the soft palate,
pharynx, and larynx. Flaccid weakness and atrophy of the sternocleidomastoid and
trapezius muscles and the tongue also occurs.
Vagus-Accessory Syndrome
Schmidt (vagus-accessory) syndrome is a lesion of the nucleus ambiguus and the bulbar
and spinal nuclei of cranial nerve XI. It results in ipsilateral paralysis of the soft palate,
pharynx, and larynx and in flaccid weakness and atrophy of the sternocleidomastoid and
trapezius muscles. Ipsilateral paralysis of the soft palate, pharynx, and larynx and
paralysis and atrophy of the tongue are caused by Tapia syndrome (vagohypoglossal
syndrome), a tegmental lesion in the lower third of the medulla that involves the nucleus
ambiguus and the hypoglossal nerve.
Vernet Syndrome
Vernet syndrome, a lesion at the jugular foramen, can be a result of a vascular lesion, a
tumor, aneurysm of the internal carotid artery, thrombosis of the jugular bulb,
tuberculosis, or syphilis. The most common cause, however, is basilar skull fracture,
which produces ipsilateral paralysis of cranial nerves IX, X, and XI. Villaret syndrome is
a lesion of the retropharyngeal or retroparotid space that causes ipsilateral paralysis of
cranial nerves IX, X, and XI and of cervical sympathetic fibers, producing Horner
syndrome.
Collet-Sicard Syndrome
Collet-Sicard syndrome is similar to Villaret syndrome, but there is no Horner syndrome.
Glossolaryngoscapulopharyngeal hemiplegia is caused by a complete lesion of cranial
nerves IX through XII.
Garel-Gignoix Syndrome
Garel-Gignoix syndrome involves the vagus and accessory nerves below the jugular
foramen (9,10).
TUMOR
Otolaryngologic symptoms can be caused by tumor involvement of nerves of the head
and neck region.
Glioma
Two percent of gliomas among children are pinealoma. The patient has extraocular
muscle involvement, ptosis, restriction of upward gaze, and bilateral hyperacusis. Some
patients have sexual changes and macrogenitosomia praecox. Central nervous system
tumors among adults usually are supratentorial.
Meningioma
Meningioma constitutes 15% of intracranial tumors. These usually slow-growing tumors
originate in the sagittal sinus, the sphenoid ridge, or the olfactory groove. If the tumor
arises on the sphenoid ridge, there may be unilateral exophthalmos and oculomotor nerve
involvement with subsequent diplopia and vision loss. Signs of olfactory groove
involvement are unilateral or bilateral anosmia and mental or personality changes. There
may be optic atrophy late in the course.
Kennedy Syndrome
Kennedy syndrome is associated with a tumor in the olfactory groove. Findings are optic
atrophy on the side of the tumor and papilledema on the opposite side.
Acoustic Neuroma
Acoustic neuroma originates along the vestibular nerve. Two percent of intracranial
tumors are acoustic neuroma. Vertigo with or without tinnitus usually is the first
symptom, and recurrent episodes presumed to be benign can occur. The patient later has
hearing loss, ipsilateral corneal hypesthesia, and incoordination of cerebellar origin. Late
in the course of acoustic neuroma, ipsilateral facial paresis develops. Because the tumors
are most frequently on the vestibular portion of cranial nerve VIII, canal paresis with
caloric testing is an early finding.
Nasopharyngeal Carcinoma
Nasopharyngeal carcinoma can include extension of central nervous system tumors into
the nasopharynx and sinuses. Tumors in this region can impair hearing. Extension of
nasopharyngeal tumors can cause Garcin syndrome, which is paralysis of cranial nerves
III through X. The effects usually are unilateral but can be bilateral. This condition is
caused by lesions in the retropharyngeal space, usually produced by infection in this area
but also caused by granuloma or metastasis or extension from the nasopharynx.
Epidermoid Tumor
Epidermoid tumors are the third most common primary mass lesion of the
cerebellopontine angle. The patient may have multiple cranial nerve palsies with or
without brainstem involvement. Hearing loss generally appears late in the course of the
tumor.
Metastatic Tumor
Metastatic tumors tend to have a rapid course, and evidence of neoplasia elsewhere
usually can be obtained. Multiple upper and lower cranial nerve palsies usually evolve.
Glioma from the brainstem or cerebellum also can invade the cerebellopontine angle,
producing symptoms of a cerebellopontine angle mass lesion. Aneurysms also may
appear in the cerebellopontine angle.
Tumor of the Glomus Jugulare
Tumor of the glomus jugulare involves cranial nerves IX, X, and XI at the jugular
foramen. There often is evidence of dysfunction of cranial nerves VII and VIII.
Pituitary Adenoma
Pituitary adenoma can be classified as functional (secreting) or nonfunctional
(nonsecreting). Prolactinoma is the most common pituitary tumor and occurs most
frequently among young women. Symptoms are galactorrhea with or without
amenorrhea. Most patients respond to medical treatment with bromocriptine. Growth
hormone adenoma causes gigantism among children before closure of the epiphyses of
the long bones. Adults have acromegaly and enlargement of the jaw, hands, and feet.
Other signs are hyperhidrosis, hypertrichosis, diabetes, cardiac disease, and paresthesia,
such as carpal tunnel syndrome.
Corticotropin-secreting tumors manifest as Cushing disease, which is characterized by
truncal obesity, moon facies, buffalo hump, pigmented stretch marks, hypertension, and
hirsutism. The lesions usually manifest as microadenomas. Nelson syndrome,
hyperpigmentation, and increasing sellar size can occur after bilateral adrenalectomy for
corticotropin-secreting tumors. In these patients, the tumors are large and aggressive.
Nonfunctional pituitary tumors manifest as decreased hormonal function or without
endocrine deficiencies. Patients often have panhypopituitarism with visual symptoms.
The patient may have increased intracranial pressure or extraocular muscle palsy. The
visual symptoms are caused by suprasellar extension of the adenoma, which affects the
optic chiasm. This causes bitemporal hemianopia and progressive loss of visual acuity.
Extraocular muscle palsy is caused by lateral extension of the tumor toward the
cavernous sinus (6,9).
FACIAL PAIN
Sinusitis is a common cause of facial pain and headache. Trigeminal neuralgia, usually
induced by palpation of a trigger zone, causes severe pain. Sphenopalatine neuralgia
(Sluder syndrome) is localized facial pain associated with vasomotor abnormality, such
as lacrimation, rhinorrhea, and salivation. The pain involves the eye, nose, palate,
maxillary teeth, ear, and temple. Glossopharyngeal neuralgia involves unilateral throat
pain associated with ipsilateral rhinorrhea, salivation, coughing, and facial burning.
Postherpetic neuralgia is similar to trigeminal neuralgia. It occurs after attacks of herpes
zoster. Trotter syndrome involves pain in the mandibular division of cranial nerve V,
unilateral deafness, ipsilateral palate hypomotility, and trismus. Ramsay Hunt syndrome
is caused by herpes zoster infection of the geniculate ganglion. Signs are vesicles on the
ear, oral mucosa, tonsils, pharyngeal mucosa, and posterior third of the tongue; facial
palsy; loss of taste; decreased salivation; palatal paralysis; and pain. Eagle syndrome is
caused by elongation and calcification of the styloid process along with calcification of
the stylohyoid ligament. Symptoms are parapharyngeal pain, dysphagia, odynophagia,
trismus, headache, and facial pain. Vail syndrome, vidian nerve neuralgia, causes
unilateral pain of the nose, eye, face, neck, and shoulder.
OTHER FACIAL SYNDROMES
Horner syndrome is caused by interruption of sympathetic pathways in the medulla,
spinal cord, and sympathetic trunk. This syndrome is characterized by constriction of
pupils, enophthalmos, ptosis, and decreased sweating of the ipsilateral face. The
gustatory lacrimal reflex (crocodile tears) is ipsilateral tearing when spicy foods are
placed on the tongue. This is caused by faulty regeneration of nerves responsible for
salivation with those responsible for lacrimation. Frey syndrome (auriculotemporal
syndrome) causes flushing, a sensation of heat, and excessive perspiration over the cheek
and pinna after ingestion of spicy food. This is caused by misdirected regeneration of
secretomotor fibers, often after injury to the auriculotemporal nerve (4).
COMPLICATIONS OF EAR AND SINUS INFECTION
Osteomyelitis
Osteomyelitis occurs through extension of infection from the paranasal and mastoid
sinuses. This usually involves the temporal, frontal, and parietal bones. Facial nerve palsy
and vertigo can be caused by osteomyelitis of the temporal bone. If it erupts into the
epidural space, the infection causes an epidural abscess. The patient has fever, malaise,
tenderness, and pain. Nuchal rigidity is rare.
Subdural Empyema
Extension of infection through the dura can cause subdural empyema. This disorder is
characterized by localized headache and can mimic mastoid or sinus infection. The
patient has fever, malaise, and decreased consciousness. Seizures, nuchal rigidity, and
other neurologic deficits follow.
Meningitis
Meningitis is the most common intracranial infection. The pia mater and arachnoid are
infected. Headache, lethargy, and irritability are early signs. Other signs of meningitis are
nuchal rigidity, limited flexion of the legs, altered mental status, and fever. Diagnosis is
made by means of analysis of cerebrospinal fluid, which shows pleocytosis (more than
1,000, mostly polymorphonuclear, leukocytes), elevated protein level, and decreased
glucose level. Antibiotic therapy should be guided by the cerebrospinal fluid culture
results.
Brain Abscess
Brain abscess forms by means of direct extension, hematogenous spread from septic
thrombophlebitis, and extension through congenital defects, traumatic fistulae, or tumors.
Brain abscess begins as localized cerebritis consisting of leukocytic infiltration and
microscopic necrosis. At this stage, it is difficult to diagnose. In 7 to 10 days, a capsule
forms, and the abscess enlarges and causes edema in adjacent tissues, producing
neurologic symptoms. Between 40% and 50% of brain abscesses are of otogenic origin.
Sinus infection accounts for about 10%. General symptoms are lethargy, headache, and
fever. Focal signs depend on the location of the abscesses. Frontal lobe abscesses, almost
exclusively the result of paranasal sinus infection, rarely have localizing symptoms.
Increased intracranial pressure, stupor, and papilledema are signs of abscesses in this
area. Brain abscesses can cause brainstem herniation and can rupture into the ventricular
system.
Orbital Cellulitis
Extension of paranasal sinusitis into the orbit can cause orbital cellulitis, which causes
chemosis, exophthalmos, diplopia, and immobility of the globe. Orbital cellulitis can
advance to orbital abscess with ophthalmoplegia, proptosis, and visual loss. Optic neuritis
characterized by acute loss of vision, decreased pupillary response, and pain with eye
movement can be caused by extension of posterior ethmoidal or sphenoidal sinusitis.
Fungal involvement with mucormycosis is a life-threatening infection associated with
diabetes mellitus and immunosuppression.
Superior Orbital Fissure Syndrome
Superior orbital fissure syndrome usually is a complication of sphenoid sinusitis. The
abducent nerve is paretic, and there may be involvement of cranial nerves III, IV, and V.
The patient has diplopia, exophthalmos, ophthalmoplegia, and decreased sensation over
the forehead.
Cavernous Sinus Thrombosis
Cavernous sinus thrombosis is the result of phlebitis spreading from the ethmoid and
sphenoid sinuses. The eye becomes proptotic and chemotic, and the eyelid is edematous.
Involvement of cranial nerves III, IV, and VI causes ophthalmoplegia (9).

HIGHLIGHTS
The cranial nerves control the special senses, movement, and
sensation of the head and neck.
Spinal nerves contribute sensation and some movement to the
head and neck.
Autonomic impulses originate in the central nervous system
fibers that lie in ganglia outside the central nervous system.
Spinal and cranial nerves carry fibers between these ganglia and
the end organs.
The cranial nerves, spinal nerves, and autonomic nervous
system are richly interconnected in the head and neck.
Several neurologic disorders and diseases manifest as ear, nose,
and throat disorders, such as dysphagia, diplopia, and vertigo.
Head and neck dystonia usually is caused by extrapyramidal
disease. It can be caused by drug intoxication, but the cause
often is unknown.
The deficits caused by tumors and CVA usually reflect the
location of the lesions. Although the symptoms of a tumor
usually are a function of tumor location, the course of the
disease may depend on the type of tumor.
Some secretory tumors and tumors in glandular structures cause
hormonal aberration.
Infection of the ear and sinuses can spread and cause neurologic
manifestations.
CHAPTER REFERENCES
1. Sooy CD, Boles R. Neuroanatomy for the otolaryngologist head and neck surgeon. In: Paparella
MM, Shumrick DA, eds. Otolaryngology: basic sciences and related principles, vol. I.
Philadelphia: WB Saunders, 1991:132134.
2. Agur AML, Lee MJ. The cranial nerves. In: Agur AML, Lee MJ, eds. Grant's atlas of anatomy.
Baltimore: Williams & Wilkins, 1999:81.
3. Appenzeller O, Oribe E. The autonomic nervous system: an introduction to clinical and basic
concepts. New York: Elsevier, 1997.
4. Waxman SJ. Basic principles. In: Waxman SJ, ed. Correlative neuroanatomy. New York:
McGraw-Hill, 1999:103122.
5. Adams RD, Victor M, Ropper AH. Multiple sclerosis and allied demyelinative disease. In: Adams
RD, Victor M, Ropper AH, eds. Principles of neurology. New York: McGraw-Hill, 1997:902
927.
6. Adams RD, Victor M, Ropper AH. Degenerative diseases of the nervous system. In: Adams RD,
Victor M, Ropper AH, eds. Principles of neurology. New York: McGraw-Hill, 1997:10461107.
7. Lee KJ, Goodrich I, McVeety JC. Related neurology. In: Lee KJ, ed. Essential otolaryngology:
head and neck surgery. New York: McGraw-Hill, 1999:341354.
8. Milhorat TH, Chou MW, Trinidad EM, et al. Chiari I malformation redefined: clinical and
radiographic findings for 364 symptomatic patients. Neurosurgery 1999;44:10051017.
9. Adams RD, Victor M, Ropper AH. Cerebrovascular disease. In: Adams RD, Victor M, Ropper
AH, eds. Principles of neurology. New York: McGraw-Hill, 1997:742776.
10. Lees P, Davis A. Postoperative meningitis. In: Johnson J, Yu VL, eds. Infectious diseases and
antimicrobial therapy of the ears, nose and throat. Philadelphia: WB Saunders, 1997:583586.
11. Riley DE, Lang AE. Movement disorders. In: Bradley WG, Daroff RB, Fenichel GM, et al., eds.
Neurology in clinical practice. Boston: Butterworth-Heinemann, 1991:15801582.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

10 OPHTHALMOLOGY
Head & Neck SurgeryOtolaryngology
10




OPHTHALMOLOGY
JEAN EDWARDS HOLT

J.E. Holt: Department of Ophthalmology, The University of Texas Health Science Center, San Antonio,
Texas.


The Eye Examination
Visual Acuity
External Inspection and Pupil Examination
Motility
Intraocular Pressure
Ophthalmoscopy
Visual Abnormalities
Physiologically Decreased Vision
Pathologically Decreased Vision
Diplopia
Red Eye
Eyelid Abnormalities and Blepharitis
Conjunctivitis, Episcleritis, and Scleritis
Keratitis
Iritis and Iridocyclitis
Miscellaneous Causes
Guidelines for Treatment
Ocular Trauma
History and Examination
Orbital Trauma
Eyelid Laceration
Superficial Injuries of the Cornea and Conjunctiva
Blunt Trauma
Penetrating Injuries
Burns
Pediatric Ophthalmology
Congenital Abnormalities
Strabismus
Esotropia
Pseudostrabismus
Exotropia
Amblyopia
Detection
Treatment
The Eye in Systemic Disease
Neurologic Disease
Thyroid Ophthalmopathy
Collagen Vascular Disease
Systemic Infection and Metastatic Cancer
Blood Dyscrasia
Ocular Side Effects of Medication
Diabetes
Hypertension and Arteriosclerosis
Imaging in Ophthalmology
Chapter References
Abnormalities of the ocular structures produce visual dysfunction, altered appearance,
pain, or systemic symptoms. Many persons believe vision to be the most important and
comprehensive of the senses. Decreased visual acuity can indicate a blinding eye disease
that can be controlled with restoration of vision, a systemic disease that can endanger life
if not detected and managed, a tumor or other disorder of the central nervous system that
can threaten vision and life, or a simple refractive error, correction of which simplifies
the patient's life. Ocular symptoms bring the patient rapidly to the physician because the
eyes are the focus of a patient's perception, and alterations in these structures usually are
not ignored.
The otolaryngologisthead and neck surgeon often joins the ophthalmologist in a team
approach to care for a patient with congenital or acquired abnormalities of the orbit and
adnexa and periorbital structures. Appreciation of the fundamental concepts of vision,
ocular anatomy and physiology, and local and systemic disorders is essential to direct
care or assist in caring for a patient with ophthalmic problems. Consultation with an
ophthalmologist is mandatory for most disorders and can be quite helpful for most
patients. This chapter highlights the most common disorders seen by otolaryngologist
head and neck surgeons and explains what often are considered to be complicated and
sophisticated problems. Also discussed are the best imaging studies for the diagnosis of
ophthalmologic and orbital disorders, trauma, and tumors.
THE EYE EXAMINATION
The three reasons for performing an ocular examination are as follows:
1. Presenting symptoms clearly related to ocular structures, such as pain in the eye
and halos around lights
2. Presymptomatic screening to detect controllable eye disease, such as amblyopia
and glaucoma
3. Evaluation or diagnosis of systemic disease mirrored in the eye, such as
retinopathy in diabetes and tuberculous choroiditis with fever of undetermined
origin
With these goals in mind, it is obvious that testing the function of the visual system and
looking at the eyes should be part of any complete medical examination.
An eye examination begins with obtaining a history related to the symptoms. Relevant
areas are chronology, eye history, family history, concurrent systemic diseases, present
use of medications, and existence of allergies. Ocular symptoms usually can be classified
into three groupsaltered visual function, abnormal sensation, or altered appearance.
Abnormalities in visual functioning generally reduce vision, cause superimposed visual
phenomena, or produce diplopia. Abnormal sensation in or around the eye can take many
formsdeep pain, which signifies intraocular or orbital inflammation; foreign-body pain
related to trauma; superficial pain of mild conjunctivitis; vague discomfort known as
asthenopia, or eyestrain, with prolonged, intensive use of the eyes; headache related to
neurologic disease or tension; or photophobia or ocular pain with exposure to light, most
commonly related to corneal abnormalities (1). Altered appearance usually refers to
eyelid abnormalities, orbital deformities, motility disturbances, or redness of the eyeball.
Visual Acuity
An eye examination begins with determining the visual acuity of each eye with the other
eye completely covered. Although measurements are obtained at distance and near, with
and without refraction (glasses), the most important determination of general eye
condition is the best-corrected-distance visual acuity, usually assessed with a Snellen
chart. Examination of children often requires pictures or individual E charts. Each line on
the chart is meant to be read by a person with normal sight at 20 feet (6 m). The largest
letter should be seen at 200 feet (60 m) by a person with normal vision. If a patient can
see that letter at a distance of 20 feet and is unable to see any of the smaller letters, vision
is 20/200. If the line read by a person with normal sight can be seen at 20 feet, and the
patient is 20 feet from the chart, the vision is 20/20. If the patient is unable to read the
largest letter on the chart, the distance at which he or she can count fingers accurately is
recorded. If the patient cannot count fingers, the distance at which hand movements are
perceived is determined. If this is not possible, whether the patient can perceive light is
documented. Table 10.1 compares visual acuity with visual ability or disability. Vision is
not a true fraction. In other words, 20/40 vision does not mean 50% of normal vision but
that the patient can see at 20 feet what a person with normal sight can see at 40 feet (12
m). If the patient can see the 20/20 line wearing glasses, his or her functional vision is
probably just as good as that of someone who sees the line without glasses.

TABLE 10.1. CORRELATION OF VISUAL
IMPAIRMENT WITH VISUAL DISABILITY



The ophthalmologist uses the process of refraction to determine the refractive error or the
lenses needed for the eye. The need for refraction is determined with a pinhole test. The
patient views a chart through a 1-mm pinhole, which reduces the blur of the image on the
retina and appreciably increases visual acuity if it is decreased owing to a refractive
problem. This test helps to rule out retinal or optic nerve dysfunction as a cause of
decreased vision. Measurement of best corrected visual acuity is an important concept.
Often patients say they are blind without their glasses. They should be informed that
vision can be physiologically abnormal without pathologic consequence.
Peripheral vision, or side vision, can be evaluated with visual field testing. This test can
be performed with various instruments, but it is commonly performed with the
confrontation technique. The patient is asked to fix on the examiner's nose with one eye
and to cover the other eye. A test object or finger is brought in from the side until the
patient reports it is being seen. The visual field is approximately 90 degrees on the same
side but only 50 degrees on the opposite side of testing. Abnormalities of peripheral
vision often are detected only through examination because patients report loss of central
vision, but loss of peripheral vision is not easily detected. Performing this test for each
eye is a good screening method for many neurologic diseases.
External Inspection and Pupil Examination
Inspection of the external eye structures includes the eyelids, eyelashes, lacrimal
apparatus, cornea, conjunctiva and sclera, anterior chamber, and iris, as well as the
general symmetry of the face and orbits. Much information can be obtained with this
examination, which often reveals the diagnosis. Particular notice should be taken of
abnormal alignment of the eyelids (ptosis or lid retraction), the position of the eyelids
against the globe (entropion or ectropion), and abnormal direction of the eyelashes
(trichiasis). Swelling in the medial canthal area can indicate abnormal lacrimal drainage.
Proptosis always is an important finding (Fig. 10.1). The causative factor may indicate
orbital or systemic disease. Specific abnormalities in the color and contour of the
conjunctiva, cornea, and sclera are discussed later with red eye. Of particular importance
is estimation of the depth of the anterior chamber in detecting an important form of
glaucoma. This test can be performed with side-illumination with a penlight. If the
anterior chamber is of normal depth, the entire surface of the iris is illuminated. If the
anterior chamber is shallow, the iris on the opposite side of the pupil is in shadow.

FIGURE 10.1. Proptosis of the left eye, viewed from
anterior (left) and superior (right) positions.



Examination of the iris usually centers on assessing the pupillary response. When light is
shone into the eye a normal pupil constricts and then redilates after the stimulus is
removed. This is the direct light reflex. The fellow pupil constricts also, and this is known
as the consensual light reflex. These reflexes should be brisk and approximately equal.
Pupillary constriction also is part of the near-vision complex associated with the process
of accommodation. If the pupil reacts to accommodation but not to light, it is the classic
Argyll Robertson pupil, often associated with syphilis. Marcus Gunn pupil is an
important physical sign in an evaluation for neurologic disease. It is elicited with the
swinging flashlight test. Light is shone in one pupil for 2 or 3 seconds and then rapidly
switched to the second eye. There should be prompt constriction if the pupil is normal. If
there is optic nerve disease or injury, the pupil gradually dilates, indicating a decreased
direct light reflex. This sign is positive early in the disease, when vision still is 20/30 or
better. Abnormal pupillary reaction in any form generally indicates serious disease. For
the physician, normal visual acuity and normal pupillary responses are comforting
findings in evaluating eye problems.
Motility
Six muscles surrounding each eye are responsible for ocular motility. Several terms are
used to describe various eye movements. The movement of one eye from one position to
another is called duction. The simultaneous movement of both eyes from the primary,
straight-ahead position to a secondary position (up, down, right, left) is called version.
Vergence is the term applied to simultaneous rotation of both eyes inward (convergence)
or outward (divergence). Evaluation of the extraocular muscle function is begun with
general inspection to find any gross deviation of either eye (heterotropia). The patient is
asked to look up, down, right, and left to reveal whether the deviation is the same in all
fields of gaze (concomitant) or varies (nonconcomitant and usually neurologically
significant) (Fig. 10.2). During these gaze movements, involuntary eye jerks, called
nystagmus, also can be detected.

FIGURE 10.2. Heterotropia is characterized by gross
asymmetry of eye movement.



The flashlight used to evaluate pupillary reflexes also can be used to assess the corneal
light reflex. The light should be symmetrically reflected in each pupil. If there is
deviation, the degree of abnormality can be estimated by the asymmetry of the light
reflex.
The cover test is used to evaluate motility. The patient is instructed to fix on an object. If
both eyes appear straight (orthotropia), cover either one. If under cover the eye deviates,
phoria, or latent deviation that becomes evident only when vision is interrupted, has been
elicited. Usually the eye resumes fixation when uncovered. If one eye is obviously
deviated, the straight-ahead eye is covered. If the deviated eye rapidly moves to resume
fixation, it most likely has good visual potential. The deviation can be eso (inward), exo
(outward), hyper (upward), or hypo (downward).
Intraocular Pressure
Measurement of intraocular pressure (IOP) should be a part of every general physical
examination. The examiner can estimate IOP digitally by placing the tips of the index
fingers on the patient's closed eyelids. All but gross abnormalities remain undetected
when this technique is used. Tonometry is estimation of IOP with an instrument. It can be
performed with an indentation technique or an applanation technique. The former is used
in the general screening process and performed with a Schiotz tonometer. With the
patient in a recumbent position, a drop of topical anesthetic is instilled into each eye. The
patient is instructed to look straight ahead with both eyes open. Assistance in holding the
eyelids open, with pressure on the orbital bones only, may be needed. The plunger is
gently placed on the center of the patient's cornea, and the corresponding scale reading is
recorded. The test should require only 1 to 2 seconds of contact with the cornea. Normal
IOP usually is 15 3 mm Hg, with an upper limit of 22 to 23 mm Hg.
Ophthalmoscopy
The final part of a general eye examination is ophthalmoscopy. It is used to evaluate the
internal structures of the eye, primarily the retina, retinal blood vessels, and optic nerve.
A direct ophthalmoscope is used for this examination and provides an upright 15
magnified image. There is great limitation of the field of view and the information
obtained if the examiner is viewing through a small pupil. A 3-mm pupil gives only a 4-
degree field of view, but a 7-mm pupil allows a 30-degree field of view. Therefore,
routine dilation of the pupils with 0.5% or 1% tropicamide or 2.5% phenylephrine is
recommended with the following exceptions: known narrow-angle glaucoma, neurologic
or neurosurgical observation, and some types of intraocular lens implants after cataract
surgery. In rare instances, dilation of the pupil can precipitate an attack of acute angle-
closure glaucoma that was previously unsuspected. This should not be considered a
contraindication. Because this form of glaucoma is rare and can be managed effectively,
the benefits of improved ophthalmoscopy through dilated pupils outweigh the risks.
The examiner holds the ophthalmoscope in the right hand and uses the right eye to
examine the patient's right eye. With the pupil dilated, reflected light from the ocular
fundus produces a clear red reflex when viewed through the ophthalmoscope with a +6
lens at a distance of approximately 1 foot (0.3 m). Any alteration in the red reflex
indicates abnormality in one of the optical structures of the eye and is always important.
The patient's eye is then approached as closely as possible as the power of the lens in the
ophthalmoscope is reduced until the optic disk comes into focus. The nerve head should
be evaluated for color, sharpness of margins, and appearance of the central depressed
area known as the cup. Systematic examination of the retinal vessels and background
then is performed. The macular region deserves special attention for patients with vision
loss.
VISUAL ABNORMALITIES
Physiologically Decreased Vision
Refractive Error
A common cause of poor vision is refractive error or change in refractive error. Patients
with myopia (nearsightedness) have an eye that is too long for its refractive system. This
typically young patient reports not being able to see the blackboard and having to sit in
the front of the schoolroom. Simple prescription of concave lenses usually restores visual
acuity to normal. Persons with hyperopia, or farsightedness, have an eye that is too short
and need simple convex lenses to bring near objects into focus. Aphakia is a special form
of hyperopia in which the refractive power of the eye is too weak because of removal of
the lens. Astigmatism is nonspheric curvature of the cornea and is extremely common
with any refractive error.
Refractive visual surgery, also known as refractive or radial keratotomy, is becoming
increasingly common among patients with myopia. Patients seeking elective reduction of
physiologic myopia usually are treated with a protocol of therapy that involves
performing radial incisions in the cornea to alter its curvature. Newer technology such as
manufacture of finer, thinner blades, more accurate blade placement, and computed
topography of the corneal surface, have helped to reduce complications and produce
more consistent results, including a decreased trend toward a hyperopic drift with time
(2). Some patients need additional incisions, called enhancements.
Presbyopia
Presbyopia is the term used to describe the clinical need for reading glasses or bifocals as
the patient enters the fourth and fifth decade of life. The crystalline lens hardens with age
and becomes less elastic, decreasing ability to accommodate or focus for near vision.
This is a normal physiologic mechanism and should not be considered a sign of disease.
Pathologically Decreased Vision
Gradual Loss of Vision
In evaluating reduced vision in pathologic terms, best corrected visual acuity must be
considered to eliminate the physiologic abnormalities. The three most common causes of
gradual loss of vision are cataract, senile macular degeneration, and glaucoma.
Cataract formation, the loss of transparency of the crystalline lens, is common. Increased
density of the lens fibers and changes in protein content occur almost without exception
to some degree in every person with increasing age; however, many times the loss of
transparency is so marked that visual function is seriously hampered. The term cataract
usually is reserved for the latter situation. Cataract formation usually is evolutional, but it
occasionally has a specific cause, such as galactosemia, galactokinase deficiency,
diabetic ketoacidosis, or trauma. If one of these metabolic abnormalities can be corrected
early in the course of cataract formation, the lens opacity can be reversed; however, often
there is no known way to prevent or reverse lens changes due to cataract. Treatment is
surgical removal of the cataract. The need for surgery usually depends on the patient's
visual requirements and desires. In rare instances, the cataract damages the eye because
of high pressure from rapid swelling and may have to be removed for other than optical
reasons.
The operation usually is performed by means of opening the anterior capsule and
extracting the lens material. The posterior capsule is left intact (extracapsular technique
or phacoemulsification). After a person is aphakic, the optical power of the lens must be
replaced to provide focusing ability. The patient can be fitted with spectacles or contact
lenses after the eye has healed or can have an intraocular lens implanted during the
surgical procedure. It is comforting to inform patients that cataract surgery is one of the
most successful operations performed.
A second common cause of gradual progressive decrease in vision among older persons
is senile macular degeneration. The cause of this condition is unknown, but it may be
related to a decrease in the blood supply to the macular area associated with hardening of
the arteries in the back of the eye, which begins as a pigmentary disturbance in the
macula and usually progresses slowly but steadily with increased scarring and often
hemorrhage into the tissues. The disease is bilateral but usually asymmetric. There is no
effective treatment, and normal use of the eyes, as for sewing and reading, does not
accelerate the process. Patients should be assured that macular degeneration is not a
blinding disease because the peripheral vision is not disturbed. Patients with this
condition always are able to move around unaided, even though their useful reading
vision may be markedly decreased. Unlike the two aforementioned visually disabling
conditions, glaucoma characteristically produces a decrease in peripheral visual ability,
but good reading vision is maintained until late in the disease.
Sudden Loss of Vision
Sudden loss of vision is a dramatic event and usually represents an identifiable pathologic
process (3). Some processes can be controlled to allow restoration of vision, and others
produce permanent loss of visual function. Vitreous hemorrhage unrelated to trauma can
occur in advanced diabetes mellitus as a result of disease of the retinal blood vessels. The
vitreous haze prevents complete examination of the retinal blood vessels, and the
offending area often remains unidentified until the blood is reabsorbed. It can take
months or years for the vitreous to clear in a relatively young person, producing marked
disability.
Central retinal arterial occlusion causes total and permanent loss of vision and abolition
of the direct pupillary reaction to light. At ophthalmoscopic examination, the fundus
appears pale with development of a cherry red spot in the macula. The spot is caused by
continued choroidal blood supply to the macula and the contrasting loss of circulation to
the rest of the retina. The retinal arteries are narrow and may have fragmented blood
columns (boxcar sign). The cause usually is an embolus from diseased carotid arteries,
abnormal heart valves, or thrombosis from long-standing atherosclerosis. In rare
instances, central retinal arterial occlusion is a vasospastic event associated with an
inflammatory disease. Treatment aimed at relieving the obstruction through vasodilation,
such as medication, ocular massage, and inhalation of 5% carbon dioxide and 95%
oxygen, usually is unsuccessful. Attacks of amaurosis fugax and central or branch retinal
artery occlusion have been shown to be related to internal carotid artery stenosis of more
than 50% diameter reduction and occlusion (3). There appears to be an increase in
ulcerated free plaque surfaces, which might lead to arterioarterial embolization. Duplex
ultrasonography and continuous-wave Doppler ultrasonography can be used for
noninvasive diagnosis; however, the magnetic resonance angiography is rapidly gaining
favor as a sensitive screening test for carotid stenosis.
Central retinal venous occlusion is more common and less dramatic than arterial
occlusion, and it has a markedly better prognosis. At ophthalmoscopic examination, the
fundus has a dramatic appearance, as if the entire view has been splattered with blood,
and the observed vessels appear engorged and tortuous. Much of the hemorrhage clears
with time, vision returns, and late complications of retinal anoxia are managed by the
ophthalmologist.
Retinal detachment occurs among approximately 1 in 1,000 persons. It is much more
common among persons with high myopia (those with large eyes), after cataract surgery
(1 of 100), and in association with trauma. The mode of visual loss varies. The patient
commonly reports a shadow or curtain in front of the eye, ascending or descending,
depending on the direction of the separation. There may be associated flashing lights and
floaters as the retinal structure is disturbed. After the macula becomes detached, central
vision is abruptly lost. At ophthalmoscopy, the detached retina is found to be pale and
wrinkled and to project forward into the vitreous, often to the point at which it may not be
focused with the attached area. Surgical reattachment of the retina is successful in 60% to
80% of cases, but return of vision depends on time and avoidance of late surgical
complications.
Optic nerve compromise, whether in the form of ischemia or inflammation, is not as
common as retinal detachment, but it is equally dramatic and important. A patient older
than 55 years who has sudden loss of vision and perhaps has vague arthritic symptoms,
low-grade fever, or temporal scalp tenderness, should have erythrocyte sedimentation rate
measured. If the rate is elevated, the diagnosis is most likely temporal arteritis, and the
fellow eye is at risk of parallel visual loss. Systemic glucocorticoid therapy should be
initiated to prevent the onset of the inflammation in the other eye. For a younger person,
if loss of vision is associated with edema of the optic disk, the diagnosis is probably optic
neuritis (Fig. 10.3). The prognosis for return of vision is good, but the possibility that a
demyelinating disorder such as multiple sclerosis is present must be considered.

FIGURE 10.3. Edema of the optic disk indicates optic
neuritis.



Sometimes the report of sudden loss of vision is unfounded. This usually occurs when an
older patient suddenly discovers a loss of sight that has existed for some time. Chance
occlusion of the seeing eye reveals the visual loss, which is erroneously reported as being
acute. The report of sudden loss of vision also is associated with hysteria or malingering
and the desire for secondary gain.
Transient Loss of Vision
Transient loss of vision can be part of the aura of migraine or a consequence of chronic
papilledema. Visual blackouts are common in vertebral-basilar insufficiency after at least
80% narrowing of this vascular system from atherosclerosis. These blackouts are
ominous because repeated attacks often are not transient and can be permanent.
Abnormalities in the carotid system can cause temporary, usually unilateral, loss of vision
(amaurosis fugax). There may be associated cerebral symptoms and hemiparesis.
Because 15% to 20% of these patients later have a stroke, they need a complete vascular
evaluation.
Diplopia
Diplopia is another symptom of visual abnormality. Physiologic diplopia is a normal
phenomenon in which objects not within the area of fixation are seen as double. This is
easily seen when one looks at a near object with attention directed at a distant object,
which then appears double. Usually this does not impinge on consciousness. Pathologic
diplopia is a cardinal sign of weakness of one or more of the extraocular muscles and
usually is caused by neurologic disease, trauma (Fig. 10.4), or diabetes mellitus. Diplopia
also can occur with normal muscles if the globe is displaced, as in orbital disease or
tumors that prevent proper alignment of visual stimuli. Monocular diplopia (that which
does not go away when one eye is covered) is rare and usually due to splitting of light
rays by an irregularity in the cornea, certain types of cataracts, or misaligned
photoreceptors in the macula. More commonly, monocular diplopia is a neurotic or
functional disorder.

FIGURE 10.4. Diplopia due to trauma that entrapped the
right inferior rectus muscle in an orbital blowout fracture.



RED EYE
The otolaryngologisthead and neck surgeon occasionally encounters a patient with a red
eye, possibly in conjunction with another disease or after treatment. The condition
causing the red eye often is a simple disorder, such as blepharitis or infectious
conjunctivitis, that resolves spontaneously or is easily managed by the physician. In some
instances, however, the condition causing the red eye is a more serious disorder, such as
intraocular inflammation or acute glaucoma. A patient with one of these vision-
threatening conditions needs the immediate attention of an ophthalmologist. The primary
physician must be able to differentiate minor irritation and a serious eye disease. Red eye
can be caused by infection, inflammation, or allergic reaction of the eyelid, adnexal
structures, or intraocular tissues. Other important causes are acute glaucoma, trauma, and
various systemic diseases.
Eyelid Abnormalities and Blepharitis
Many common disorders affect the eyelids. A sty (hordeolum) is an acute infection of
one of the glands in the eyelid, similar to a boil or furuncle of other areas of the skin. The
patient typically has a red eyelid with moderate tenderness and swelling in the involved
area. There may be associated redness of the conjunctiva. These lesions usually are self-
limiting and drain spontaneously, or the patient can be treated with warm compresses and
topical antibiotics. A chronic lipogranulomatous structure known as a chalazion can be
caused by an abnormality in the meibomian glands of the eyelid. If the patient requests
treatment, this lesion usually necessitates surgical incision and drainage. Diffuse
inflammation or infection of the eyelids is known as blepharitis. It characteristically has
two forms. The first is a chronic staphylococcal infection of the glands surrounding the
eyelashes. Abnormal oil secretions from these glands irritate the eye and cause redness
and sometimes small whitish infiltrates in the cornea near the limbus. The other form is
blepharitis associated with typical seborrhea of the scalp, eyelashes, and eyebrows. These
conditions tend to cause swelling of the eyelids, a moderate amount of erythema of the lid
margins, and mild to moderate conjunctival injection. The patient describes having
irritated eyes with scaling or crusting of the eyelashes. Treatment is long term and is
directed at eradicating the contaminated flora, controlling the scalp seborrhea, and
cleaning the lids. Anatomic abnormalities of the eyelids, such as entropion with irritation
due to misdirected eyelashes or ectropion, which causes poor tear function and corneal
exposure, can be eliminated as the cause of redness by simple observation.
Conjunctivitis, Episcleritis, and Scleritis
Conjunctivitis is inflammation of the mucous membrane covering the globe and lining
the inner part of the eyelids. Conjunctivitis usually is infectious or allergic. Viral
conjunctivitis caused by the adenovirus group is the common pink eye for which children
are sent home from school. Symptoms are mild, with only diffuse redness of the
conjunctiva, minimal clear discharge, and perhaps a tender preauricular node or
associated pharyngitis. The condition is generally self-limited, but it is highly contagious
in its early stages. Bacterial conjunctivitis is commonly caused by strains of
Staphylococcus, Diplococcus, or Haemophilus. The patient has mild symptoms of
grittiness and photophobia. The most characteristic finding is that the lids stick together
overnight because of a mucopurulent discharge. If acute, copious purulence is present,
the offending agent may be Neisseria gonorrhoeae, and further systemic investigation
should be performed. Routine culturing is not necessary because there usually is a prompt
response to broad-spectrum topical antibiotics. If symptoms persist for more than 2
weeks, an alternative diagnosis should be entertained.
Allergic conjunctivitis can occur in response to topical medications, cosmetics, aerosols,
or as part of the hay fever complex. The first exposure can be dramatic with severe
itching and profuse watering associated with marked edema of the conjunctiva
(chemosis), and the eyelids may be swollen shut, similar to the reaction of an insect sting.
This condition can be unilateral or bilateral. It usually is managed with cold compresses
and perhaps topical or systemic antihistamines after elimination of the offending agent, if
possible.
Deep to the conjunctiva are the episcleral tissues and sclera. If the inflammation is not
superficial, the patient reports deep pain, and the erythema appears dark red or purplish,
episcleritis or scleritis should be considered. Episcleritis usually is an isolated patch of
inflammation without sequelae. In contrast, more than 50% of cases of scleritis are
associated with systemic disease, usually of a rheumatic nature. Recurrent inflammation
of a pterygium can produce a discrete area of conjunctivitis.
Keratitis
Keratitis is inflammation of the cornea. Although often mild, this condition can be
dangerous and threaten vision. Disruption of and infiltrates in the cornea always produce
pain, photophobia, and decreased vision. The conjunctiva is injected, and iritis may be
present. Keratitis caused by the herpes simplex virus is an important ocular condition.
The infection typically forms a branching dendritic pattern on the cornea. If recognized
before corneal scarring occurs, the infection can be controlled with any of several
antiviral medications. Iridocyclitis can be caused by the herpes zoster virus, which affects
the ciliary body and the skin of the tip of the nose along the nasociliary nerve. Bacterial,
viral, or fungal corneal ulcers are serious conditions that necessitate intense therapy and
cause prolonged morbidity. Ulcers caused by Pseudomonas organisms sometimes
progress to perforation in 24 to 48 hours despite intense therapy. Because any disruption
of the corneal epithelium can allow entrance of organisms, infection must be considered,
particularly after trauma and in the treatment of debilitated patients with a poor tear film.
Iritis and Iridocyclitis
The iris and ciliary body anatomically constitute the anterior uveal tract. Uveitis is a
general term that describes inflammation of the iris (iritis), ciliary body (cyclitis), or most
commonly both (iridocyclitis). Acute iridocyclitis causes severe aching of the eye,
intense photophobia, tearing, and in many instances, decreased vision. The redness
usually is most evident around the limbus over the ciliary body (ciliary flush), unlike the
diffuse redness of conjunctivitis. The pupil is constricted owing to direct irritation of the
iris sphincter muscle, and the anterior chamber fluid is cloudy owing to the presence of
inflammatory exudate and cells entering the aqueous. Severe secondary glaucoma can
occur if clumps of this debris block the filtration angle. In most acute cases of iritis not
associated with severe corneal disease or trauma, the cause is unknown but the condition
may be associated with tuberculosis, sarcoidosis, ankylosing spondylitis, rheumatic
diseases, gonorrhea, or Reiter syndrome.
The objective in managing iritis is suppressing inflammation and easing pain due to
spasm in the ciliary body. This is achieved with topical glucocorticoids and a cycloplegic
agent. Systemic analgesics often are needed. Herpes zoster can involve the iris and
produce marked iridocyclitis. This appears to be more common with involvement of the
external nasal nerve, a branch of the ethmoid nerve, which is related to the innervation of
the iris. The herald sign of this disorder is a painful eye, usually red, which is associated
with herpetic eruption along the ipsilateral lower half of the nose. This is considered an
urgent ophthalmologic condition and should be managed by an ophthalmologist. Herpes
zoster ophthalmicus is a frequent first manifestation of acquired immunodeficiency
syndrome (AIDS) or human immunodeficiency virus infection (4,5). Acute retinal
necrosis also may be present. Herpetic lesions of the face have the highest association
with AIDS. An underlying immunodeficiency syndrome should be suspected and
investigated when herpetic lesions involve the eye.
Miscellaneous Causes
Several other important pathologic processes must be considered in the differential
diagnosis of red eye. If there is a history of trauma, a foreign body or abrasion must be
considered. Patients with acute angle-closure glaucoma have severe pain, a cloudy
cornea, a dilated and sluggish pupil, a marked decrease in vision, and an increase in IOP.
Dacryocystitis (inflammation of the lacrimal sac) is characterized by painful swelling and
erythema in the medial canthal area, which can cause systemic symptoms with fever and
marked leukocytosis. Treatment consists of heat, antibiotics, and drainage, if needed.
Orbital cellulitis is a serious condition and can be life threatening among children and
persons with suppressed immune function (Fig. 10.5). If ocular motility is limited,
attention must be given to monitoring pupillary reaction and observation for optic nerve
compression as an ominous sign of visual loss. A red eye associated with sudden
proptosis is a sign of serious orbital or cavernous sinus disease (Fig. 10.6). Table 10.2
and Table 10.3 summarize the signs and symptoms helpful in the differential diagnosis of
red eye and the indications for referral (Table 10.2 and Table 10.3).

FIGURE 10.5. Orbital cellulitis.



FIGURE 10.6. Proptosis, chemosis, and redness of left
eye suggest serious orbital or cavernous sinus disease.



TABLE 10.2. SYMPTOMS OF RED EYE



TABLE 10.3. SIGNS OF RED EYE



Guidelines for Treatment
Adult patients with bacterial conjunctivitis are treated with antibiotic drops rather than
ointment except at bedtime. Children are treated with ointment. A 10% to 15% solution
of sodium sulfacetamide given four times daily for 4 days is recommended unless the
patient has a sulfa allergy. Patients with sulfa allergies can be treated with tobramycin,
gentamicin sulfate, or another topical solution may be substituted. Neomycin compounds
are to be avoided because of the high incidence of allergy and contact dermatitis.
Cycloplegic eyedrops, such as atropine, homatropine, or cyclopentolate hydrochloride,
are used to reduce ciliary spasm to decrease pain. If these agents are prescribed, the
patient must be warned of the side effects of decreased near vision and pupillary dilation.
Topical anesthetic drops should be used for diagnosis only. Prolonged use can slow
corneal healing and cause severe allergic reactions. Because these agents eliminate
corneal sensation, the protective blink reflex is retarded, opening the door to dehydration
and injury.
Administration of topical glucocorticoids should be reserved for the ophthalmologist. If
the condition is one best managed with glucocorticoids, the patient should be examined
and treated by a specialist. Glucocorticoid eyedrops make the patient feel better, but in
conditions such as herpes simplex, keratitis, or fungal corneal ulcers, symptoms may
decrease while the cornea is melting away and threatened by perforation. Several weeks
of use of glucocorticoids can cause cataracts and elevation in IOP, which leads to typical
glaucomatous optic nerve damage and visual loss.
OCULAR TRAUMA
When a patient sustains ocular trauma, the most important task is to differentiate a
serious, potentially blinding problem and less serious problems. The care rendered by the
first physician to examine a patient with ocular trauma frequently determines the visual
outcome. A few minutes can make the difference between saving or losing sight. For
these reasons, all patients with ocular symptoms should be treated according to an
organized plan.
History and Examination
As in all specialties of medicine, a patient's symptoms and history provide clues about
what the examination may reveal. A tearing or scratchy sensation usually is trivial, but a
chemical burn or penetrating injury can be visually devastating. The physician should
always be cautious. A trivial or outwardly minor injury can be accompanied by a small
perforation of the globe or penetration of a minute foreign body into the eye. The
likelihood of perforation should always be borne in mind during examinations, regardless
of how minor the injury may appear. After the most careful examination, if there is the
slightest doubt about the presence of perforation, prompt referral to an ophthalmologist is
recommended.
A detailed history, as would be appropriate in outpatient care or in evaluating a chronic
problem, is not indicated or necessary in an emergency. Some issues are important,
however. How did the trauma happen? For example, did something blow into the eye
while the patient was walking outside, or was the patient grinding steel and struck by part
of the machinery? When did the trauma happen? The chronology of events is extremely
important. Also essential is the history of the eye. When a patient has a decrease in visual
acuity, it is important to know whether that eye has had poor vision in the past or this is
an acute change. Old trauma must be differentiated from the effects of a new injury.
After a history is obtained, careful inspection of the structures involved should be
undertaken with documentation of visual acuity. This is important from a medicolegal
point of view, and it is helpful in ascertaining the extent of the injury and monitoring of
treatment. If a patient does not have his or her glasses for the examination if they were
broken in the trauma, use of the pinhole test is important in evaluating vision to obtain
the best possible acuity.
Orbital Trauma
Trauma to the orbit can be superficial, resulting in only ecchymosis of the lid (black eye),
or it can be extensive, involving the bony walls and intraocular structures. Plain
radiographs of the orbits are of limited value after orbital trauma except for localizing
embedded metallic foreign bodies. Computed tomography (CT), both axial and coronal,
provides the best information about osseous components of trauma. Soft-tissue window
algorithms can be used to assess hematoma formation, orbital fat prolapse, and other
damage. Evidence of orbital emphysema on CT scans usually is a result of orbital
continuity with fractured sinuses. Although the air usually resorbs spontaneously,
increased IOP and retinal artery compression can occur (6). Evaluation of extraocular
muscle function can show soft-tissue entrapment in an orbital floor fracture.
Subcutaneous emphysema in the eyelids can indicate a medial wall fracture into the
ethmoid air cells. Visual acuity should be documented. A decrease may indicate ocular
damage. More than 30% of injuries to the bony orbit are associated with intraocular
injury (7,8,9 and 10). If the injury is superficial or if the findings at radiography, motility
studies, visual acuity testing, and globe inspection are normal, the patient can be
reassured. Otherwise, a referral can be made for surgical care or further ocular
examination.
Eyelid Laceration
Trauma to the eyelid can be routine or quite involved. A superficial laceration, parallel to
the lid margin, is similar to a skin laceration in other parts of the body and can be
repaired in the same manner. Foreign bodies, however, can be overlooked; therefore the
wound should be explored and irrigated well before surgical closure. If the deeper
structures are involved, the anatomic relations of the levator palpebral muscle, tarsal
plates, and orbital septum must be known and the appropriate repairs performed.
Lacerations that involve the lid margin or are medial to the punctum and involve the
canalicular structures necessitate detailed surgical reconstruction. The primary repair is
extremely important because secondary scar revision and attempts to reestablish the
function of the eyelid and tear drainage apparatus are difficult. Faulty repair can produce
a notch in the eyelid that interferes with its ability to spread the tear film. Irritation and
constant tearing can be caused by loss of corneal epithelium and perhaps cause ulceration
of the cornea. Involved lacerations therefore should be managed by a surgeon
knowledgeable in the anatomic and physiologic characteristics of the eyelids.
Superficial Injuries of the Cornea and Conjunctiva
The cornea and conjunctiva, although important, are considered superficial eye
structures, and injuries to them often can be managed by a primary care physician.
Subconjunctival hemorrhage usually is without sequelae, behaving as a bruise elsewhere
on the body. The patient should be reassured that the blood clears over a 10- to 20-day
period. The hemorrhages can be caused by minor trauma or by coughing or sneezing.
They also can occur spontaneously. There is little or no value in performing hematologic
or blood coagulation studies for patients with spontaneous subconjunctival hemorrhages
unless a history of frequent recurrence is given. In those cases, the possibility of blood
dyscrasia should be considered. These patients have a bright red eye, normal vision, and
no pain. If subconjunctival hemorrhage is a manifestation of severe trauma, however, the
physician always must rule out more serious injuries to the deeper ocular structures.
Corneal or conjunctival foreign bodies first should be approached with irrigation. If this
is not successful, they can be brushed with a cotton-tipped applicator or nudged out with
a small pick or needle. One drop of topical anesthetic solution usually is all that is
necessary to manipulate the object. If a foreign body is not seen, but the symptoms or
history indicate the presence of one, fluorescein stain can be used to outline a corneal
abrasion. A small strip of fluorescein paper is moistened with sterile water, and this strip
is applied to the inferior cul-de-sac while the patient looks up or the superior cul-de-sac
while the patient looks down. When a cobalt blue penlight or Wood lamp is used,
fluorescence may outline the abrasion. If the patient wears soft contact lenses, use of
fluorescein should be avoided, because the dye can permanently stain the lenses. The
pain of corneal abrasion is sharp and stabbing. It is aggravated when the patient opens
and closes his or her eyes and is associated with marked photophobia, unlike the deep
ache of iritis and the superficial mild and intermittent discomfort of conjunctivitis.
If the abrasion is vertical over the cornea, the lid should be everted, and often a foreign
body is found under the upper lid. For lid eversion, the patient looks down while a cotton-
tipped applicator handle, pencil eraser, or finger is placed just beneath the orbital rim.
The eyelashes are grasped with the other hand and pulled straight out from the globe, the
lashes are pulled up and forward, and the eyelid flipped over with the applicator stick,
pencil, or the base of the finger as a fulcrum. The everted lid is held against the orbital
margin, and the underlying structures are examined. Approaching the patient with
confidence makes this procedure simple.
Overwearing contact lenses or excess exposure to an ultraviolet sunlamp can cause severe
punctate corneal damage with eyelid edema. Treatment usually is observation. Symptoms
appear 6 to 12 hours after exposure or after the contact lenses are taken out. The patients
experience marked light sensitivity and a feeling of sand or grit in the eyes. Superficial
pain can be severe. There is marked spasm of the lids and associated tearing. Both eyes
usually are involved.
Misplacement of contact lenses is a common emergency. The lens usually can be found
with adequate evaluation in the deep folds of the conjunctival fornices. The patient
should be reminded that if it is not found, the lens did not migrate posteriorly into the
intracranial structures but rather dropped out.
Therapy for corneal abrasions, including treatment after removal of a foreign body,
consists of antibiotic eyedrops. This is recommended if the injury was caused by
contaminated material, such as a fingernail or branch. If there is a large abrasion and the
eye is quite inflamed, a cycloplegic agent can be used to reduce the ciliary spasm and
pain (Fig. 10.7). The eye often is patched for comfort and to speed healing.
Glucocorticoids or glucocorticoids-antibiotic combinations should not be prescribed, and
topical anesthetics should not be given for home use. Most small abrasions heal in 24
hours and larger ones in less than 1 week.

FIGURE 10.7. Appearance of an injured eye with a
corneal abrasion outlined with fluorescein dye.



Blunt Trauma
A severe blow to the eye or orbit can miraculously spare the ocular structures, or it can be
devastating. The most common physical finding in cases of blunt trauma is hyphema
(blood in the anterior chamber). If an eye has suffered a blow hard enough to cause
ciliary body bleeding, which is believed to be the origin of the blood, the anterior
chamber angle structures can be disrupted and the filtration network damaged. The
patient is immediately or months to years later at risk of development of increased IOP.
Dislocated or subluxed cataractous lenses can be found. The vitreous can be detached and
become hemorrhagic. Retinal holes or detachment also can occur. Scleral rupture can
occur anteriorly or posteriorly, and the optic nerve can be contused or avulsed. Blunt
trauma to the eye necessitates complete ophthalmologic examination and can necessitate
lifelong care and follow-up evaluation.
Penetrating Injuries
After an eye has been penetrated, immediate and long-term treatment is administered by
an ophthalmologist. Accurate diagnosis and referral without manipulation or further
examination are essential in managing these injuries. If foreign bodies are partially
extruding from the eye, the diagnosis is evident. The foreign body should be left intact
and removed in the controlled environment of an operating room. A key to the diagnosis
of penetrating trauma is a peaked or teardrop pupil. If the pupil is not round and is pulled
to one side, the examiner should suspect a penetrating injury and treat the patient with
extreme care. The combination of lid laceration and hyphema also suggests penetration.
For transporting a patient with an open eyeball, an aluminum shield is taped or a cone
made from x-ray film or a plastic drinking cup is placed over the involved eye to avoid
pressure than can cause extrusion of intraocular contents. Tetanus prophylaxis is
appropriate, as with any laceration.
Burns
An emergency that often comes to medical attention too late is chemical injury. Many
substances are accidentally instilled in the eye, and most of these are of no consequence.
Serious alkali or acid burns are emergencies. In the first few minutes, the solution must
be diluted with any liquid available. It is not necessary to spend time attempting to
neutralize the solutionimmediate and profuse dilution is extremely important. Copious
irrigation should be performed for 5 minutes, the eyelids should be held forcefully apart
during irrigation. The patient can be held over a drinking fountain or under a faucet.
Topical anesthetic usually is needed to remove particulate chemical matter from the eye.
If lid spasm is severe, a selective facial nerve block may be needed to keep the eyelids
open. After the diagnosis is made and initial treatment completed, an additional 20
minutes of continuous irrigation with balanced salt solution or Ringer solution, with a
continuous intravenous drip, should be undertaken. Cycloplegic and antibiotic eyedrops
usually are administered, and a sterile eye patch is gently applied. Thermal or flash burns
of the eye and eyelid are managed with the same general measures as other skin burns.
The ocular sequelae of chemical burns can cause total blindness. Damage to the eyelids
from chemical or thermal burns usually causes severe cosmetic disfigurement, permanent
tearing, exposure keratitis, and corneal ulceration or perforation.
PEDIATRIC OPHTHALMOLOGY
As the study of childhood disease entails a distinct category of otolaryngology, problems
of the pediatric eye should be considered separately.
Congenital Abnormalities
The ocular structures often are affected in developmental abnormalities and congenital
anomaly syndromes. These range from minor cosmetic deformities to complete lack of
any visual components. Congenital glaucoma is characterized by a large eye and marked
photophobia. Childhood cataracts often are of known cause, such as manifestation of
congenital rubella or a consequence of an inborn error of metabolism. Any abnormality in
the red reflex elicited through the ophthalmoscope during examination of a newborn
should be cause for referral. The cat's eye reflex, or white pupil, suggests many serious
diseases, the most severe of which is malignant intraocular tumor of children
retinoblastoma.
Strabismus
Most of the practice of pediatric ophthalmology centers on the study of strabismus
(failure of the two eyes to look at the same object) and amblyopia, an important
preventable cause of vision loss. Strabismus is misalignment of the two eyes so that only
one eye is directed at the specific object of regard. General ocular inspection may reveal
gross deviation of one eye. The corneal light reflex allows an estimation of the amount of
the deviation. The cover test can help detect almost every case of strabismus. A small
amount of phoria is present among most patients with normal eyes and should not be
cause for alarm.
All newborns should be examined for gross alignment of the eyes. Up to 3 to 4 months of
age, children often have uncoordinated eye movements and can temporarily manifest
actual strabismus. An ophthalmologist should be consulted if occasional deviations
persist beyond this age. Infants with constant deviations should be referred at any age as
soon as possible. The determination, by examination or history, that a deviation is
intermittent is an important prognostic sign. Normal binocular vision can develop only if
there is precise coordination of the two eyes. If the mental object of regard is seen by one
eye and another object seen by its fellow, the brain suppresses the accessory image to
avoid diplopia, thereby turning off the input from the deviating eye. If the eyes are
straight at least part of the time (intermittent strabismus) or if the deviation alternates
(first one eye assumes fixation and then the other), there is a chance for full development
of visual potential.
Esotropia
Esodeviation is the most common type of strabismus, often manifesting itself soon after
birth and frequently necessitating surgery to straighten the eyes. Esodeviation also can
appear in the second or third year of life and can be associated with an attempt to focus
the eyes owing to marked refractive error, which often is corrected with glasses.
Pseudostrabismus
Among children with large epicanthal folds, the appearance of esotropia can be quite
marked, a condition called pseudostrabismus. When the folds flatten with age, the
appearance changes, leading to the dangerous misconception that children outgrow
strabismus.
Exotropia
Exodeviation is less common than esotropia. It usually occurs intermittently with fatigue,
daydreaming, or when the child is in bright sunlight.
AMBLYOPIA
Amblyopia is defined as unilateral defective vision, uncorrectable by glasses, in an
otherwise normal eye. It occurs among about 5% of the young adult U.S. population and
is commonly known as lazy eye. Half of all patients with amblyopia have or have had
associated strabismus. Refractive amblyopia occurs if there is a marked difference in
refractive errors of the two eyes. Like suppression to avoid diplopia in strabismus, the
brain turns off the blurred image because of the greater refractive error to obtain a clearer
object of regard. Occlusion amblyopia occurs if opacities of the ocular media, such as
ptosis, cataract, or a macular lesions, prevent adequate sensory input. Retinoblastoma
often manifests as esotropia due to macular involvement. All patients with strabismus
need complete dilated ocular examinations.
Detection
Amblyopia, if detected early, often is curable. Treatment rarely is successful after 9 years
of age, and best results are obtained if the patient is treated before the age of 5 years. The
key to this disease is prevention. Prompt investigation is mandatory if a child has obvious
strabismus. Even if the eyes appear straight during a routine pediatric examination, the
examiner should observe how the child watches a light, how he or she follows a moving
object, and how the child reacts to having each eye covered alternately. If amblyopia
exists, the patient probably will resent, vocally or through evasive movement, covering of
the good eye. Even before a child can give verbal response to visual acuity testing, he
or she should be able to maintain central and steady fixation with each eye. By 3 years of
age, visual acuity should be measured with picture cards or single E charts. The examiner
must be certain that only one eye at a time is participating in the test. Children always
peek if the fellow eye is not properly occluded. Young children may not quite reach
20/20, but as long as both eyes are near that standard and equal, the physician and parents
need not be disturbed. Amblyopia may be present if there is a two-line difference
between the two eyes on a visual acuity chart or if vision is only 20/30 to 20/40.
Although amblyopia is a relatively minor visual impairment, many adults with a history
of lazy eye have vision of only 20/200 or even less.
Treatment
Therapy for amblyopia is based on the simple idea of forcing the child to use the affected
eye. Proper spectacle correction is followed by patching the normally used eye. The
duration of treatment is monitored by the ophthalmologist. After maximal amblyopic
treatment, surgical correction of any residual strabismus is undertaken to prevent
recurrence of the amblyopia and to improve cosmesis and minimize psychosocial
problems. Early detection and prompt referral of patients with strabismus or amblyopia
can be one of the most important contributions of a physician treating pediatric patients.
THE EYE IN SYSTEMIC DISEASE
Neurologic Disease
The ocular manifestations of systemic disease always play an important role in general
medicine. Neurologic and neurosurgical diagnoses often are made from eye
examinations, and the disease course is monitored with an ophthalmoscope because the
eye is truly the window to the brain. Finding a fixed, dilated pupil or Marcus Gunn pupil
is important. Swelling of the optic disk or true papilledema is an important
ophthalmoscopic finding indicating increased intracranial pressure. A patient with
papilledema has normal visual acuity, elevation of the disk with absence of the cup,
blurred disk margins, venous engorgement, hyperemia of the disk, and usually
hemorrhage and exudate around the disk. The presence or absence of venous pulsation is
not a reliable sign. Inflammatory swelling of the optic disk (papillitis or optic neuritis),
commonly a result of demyelinating disease, may appear ophthalmoscopically similar,
but the patient reports markedly decreased vision due to direct nerve damage.
Optic atrophy, often described as aspirin disk, appears as a pale nerve head without
normal capillaries on the surface. The presence of an atrophic nerve is sufficient to
explain decreased visual acuity, but it represents only a physical finding and is not
sufficient to confirm a diagnosis. The cause of optic atrophy must be established from the
history or from further ophthalmoscopic or neurologic examination.
Thyroid Ophthalmopathy
Also known as Graves ophthalmopathy and thyroid orbitopathy, thyroid ophthalmopathy
can raise both functional and cosmetic concerns. Although the cause of proptosis can be a
primary or metastatic tumor, arteriovenous malformation, or carotid cavernous fistula, by
far the most common cause of unilateral or bilateral proptosis is abnormal thyroid
function. In classic Graves disease, the patient appears bug-eyed owing to
exophthalmos and eyelid retraction (Fig. 10.8). Ocular motility may be reduced because
of infiltration of the muscles and periorbital tissues with an abnormal
mucopolysaccharide substance. If the cornea becomes desiccated from exposure or if
orbital pressure increases to the point at which papilledema or optic atrophy occurs, the
condition is considered malignant and often necessitates immediate medical and surgical
therapy. Results of thyroid tests may not correlate with the progress or severity of the eye
findings, but combined evaluation and follow-up care with an endocrinologist are
encouraged.

FIGURE 10.8. Exophthalmos and lid retraction due to
Graves disease.



Collagen Vascular Disease
The external layers of the eye have a high collagen content. Inflammatory diseases that
affect this tissue, such as rheumatoid arthritis or systemic lupus erythematosus, often
cause external ocular inflammation. Keratoconjunctivitis sicca is the dry eye component
of Sjgren syndrome. Most of these diseases also have a vasculitic component, and
retinal vascular sheathing and occlusions are common.
Systemic Infection and Metastatic Cancer
Systemic infection such as septicemia often establishes a metastatic focus in the eye,
most commonly as choroiditis. Tuberculosis, syphilis, and histoplasmosis often are
diagnosed in this manner. Orbital or elevated choroidal lesions often occur with
metastatic carcinoma, especially metastasis from the lung and breast (Fig. 10.9).

FIGURE 10.9. Orbital lesion due to metastatic
carcinoma.



Blood Dyscrasia
Blood dyscrasia, such as hyperviscosity syndromes, leukemia, or sickle cell disease, has
characteristic retinal vascular patterns that may help confirm a diagnosis.
OCULAR SIDE EFFECTS OF MEDICATION
Referral to the Physicians' Desk Reference quickly makes it apparent that to avoid ocular
side effects, physicians should prescribe few or no systemic medications. The increased
IOP and cataractogenic effects of glucocorticoids have been mentioned. Ethambutol,
chloroquine, and the phenothiazines are commonly used drugs with direct toxic effects on
various ocular tissues. Patients taking these and other such medications need baseline
examinations and periodic ophthalmic evaluation.
DIABETES
Diabetes is associated with many eye changes, including transient changes in
accommodation due to fluctuations in blood glucose level, cataract, and glaucoma.
Retinopathy, however, makes diabetes the leading cause of blindness in the United
States. Retinopathy is related to the duration and the control of the diabetes. Within 15 to
20 years of the onset of diabetes, persons with juvenile- and adult-onset diabetes may
have a visual disability. Good metabolic control can delay the onset of retinopathy, but it
cannot retard the progression.
Diabetic retinopathy can be classified as nonproliferative or proliferative.
Nonproliferative or background retinopathy consists of venous abnormalities, exudate,
microaneurysms, dot and blot hemorrhage, and associated retinal edema. These are the
earliest changes characteristic of diabetes, and they begin in the posterior pole of the eye,
which is easily viewed with a direct ophthalmoscope. Patients with background
retinopathy are not treated and can be observed with routine annual or biannual
examinations. Proliferative retinopathy is the development of new fragile blood vessels
(neovascularization) in response to a hypoxic stimulus related to the disease. These
vessels bleed into the retina and cause fibrosis and retraction of the retina into a
detachment or bleed into the vitreous and cause sudden loss of vision and usually similar
intravitreal fibrosis and traction on the retina. This end stage is called retinitis
proliferans.
The only therapy for diabetic retinopathy is vitrectomy and intraocular membrane
stripping. After the onset of retinopathy, the 5-year survival rate for the eyes approaches
zero. To prevent blindness, therapy is directed at the beginning neovascularization. Laser
photocoagulation, used to burn and destroy the hypoxic retina that is theoretically
supplying the stimulus for neovascularization, is currently the most promising and most
used mode of therapy.
HYPERTENSION AND ARTERIOSCLEROSIS
Hypertensive retinopathy and the retinal vascular changes of arteriosclerosis are
characteristic. The term arteriosclerosis, not atherosclerosis, is associated with changes
in the retina. The central retinal artery usually divides into superior and inferior branches
before it is visible on the optic disk; therefore the vessels examined are arterioles. Diffuse
narrowing of the retinal arterioles is the earliest sign of hypertension, which can be
caused by the spasm of malignant hypertension of toxemia or renal disease, and is
reversible. Hypertension becomes permanent, however, if the pressure remains elevated
and is usually followed by segmental arterial narrowing, especially if the diastolic blood
pressure is or has been greater than 120 mm Hg. Further damage to the vessel walls
causes leakage of blood and plasma, forming superficial flame-shaped retinal
hemorrhages, deeper dot and blot hemorrhages, hard and waxy exudates, and soft cotton
wool exudates (retinal infarcts). As a response to increased intracranial pressure or to
anoxia of the optic nerve, papilledema develops. The 5-year mortality among patients
with papilledema related to hypertension is greater than 90%.
Retinal arteriosclerotic damage revolves around changes in vessel wall transparency and
abnormality in the arteriovenous crossings. Thickening of the arteriole wall increases in
the light reflex stripe viewed through an ophthalmoscope. The thickening progresses until
the light reflex appears to occupy the entire width of the blood column (copper wire
appearance) and on to the point at which no blood is visible at all, giving the
characteristic white sclerotic silver wire appearance. At points of arteriovenous crossing,
the vessels are in a common adventitial sheath. As the arteriolar walls thicken,
compression of the venules becomes apparent first as tapering of the ends, progressing to
banking with dilation of the venule distal to the crossing, and finally to vascular
occlusion with complete interruption of blood flow.
Separate categorization of these companion diseases can be important, even though in the
advanced stages, almost without exception, the changes occur together. Specific
hypertensive changes can alert the physician to the severity of hypertension, which can be
monitored with a sphygmomanometer. More important, the arteriosclerotic changes mark
the chronicity of the disease and mirror the condition of the vessels of the kidneys, heart,
and brain. Table 10.4 summarizes acute ophthalmic emergencies, including vascular
disorders.

TABLE 10.4. EMERGENCIES
HYPERTENSION AND ARTERIOSCLEROSIS



IMAGING IN OPHTHALMOLOGY
Magnetic resonance imaging (MRI) is the most sensitive modality for evaluation of most
disorders of the central nervous system, including stroke, white matter lesions, and
hemorrhage; however, subarachnoid hemorrhage and acute stroke are better visualized
with CT. Computed tomography also is the best imaging method for evaluation of orbital
trauma. Within the orbit, MRI clearly is most effective for imaging the soft tissues, optic
nerve, and retrobulbar space (11,12). Magnetic resonance angiography (MRA) is an
excellent screening tool for extracranial occlusive vascular disease, although it slightly
exaggerates stenotic lesions. If the carotid artery is found to be totally blocked at MRA,
the patient probably cannot undergo surgical treatment. If intracranial aneurysm is
suspected, however, conventional angiography is the standard. Magnetic resonance
imaging can be helpful in the diagnosis of craniopathy involving the orbit. For example,
in third nerve palsy, MRI can help identify brainstem infarcts, hemorrhage, and
arteriovenous malformation; lymphoma and trauma involving the subarachnoid space;
and cavernous sinus lesions such as cancer, aneurysm, and Tolosa-Hunt syndrome (13).

HIGHLIGHTS
If a person with normal sight is judged to see a certain-sized
line at 20 feet (6 m) on an eye chart, a patient in comparison
testing who can see that line at 20 feet is considered to have
20/20 vision. If the patient can only see a line at 20 feet that a
person with normal sight sees at 200 feet (60 m), then the
patient has 20/200 vision.
A Marcus Gunn pupil is detected with the swinging flashlight
test, in which light is shone in one pupil for 2 to 3 seconds and
then rapidly switched to the other eye. There should be a
prompt constriction in the normal eye, but with optic nerve
damage or injury, the pupil gradually dilates.
Sudden loss of vision can be caused by vitreous hemorrhage,
central retinal arterial occlusion, which is irreversible, central
retinal vein occlusion, which can be reversed in some cases,
retinal detachment, optic nerve compression, or cerebrovascular
accident.
Physiologic diplopia occurs if an object in the near vision
becomes double when gaze is focused on a far object.
Pathologic diplopia occurs when objects appear in the direct
fixation of gaze. It can be caused by neurologic disease, tumor,
trauma, or a metabolic abnormality.
Viral conjunctivitis as a cause of red eye is almost invariably
associated with pharyngitis and an ipsilaterally enlarged
preauricular node. It is highly contagious in its early stages.
A patient with herpes zoster skin eruptions on the tip of the
nose also may have iridocyclitis because the ciliary body and
the nasal skin are innervated by the same nerve.
Topical anesthetic drops to the eye should be used only for
diagnostic purposes. Prolonged use can retard corneal healing,
cause severe allergic reactions, and by eliminating corneal
sensation, reduce the protective blink reflex.
A horizontal laceration of the upper eyelid suggests injury to
the levator muscle. Because a foreign body penetrating the
eyelids also may have penetrated the globe, ophthalmologic
consultation is mandatory.
When vertical abrasion of the cornea is seen, it is likely that a
foreign body is trapped in the upper eyelid. The eyelid should
be completely everted and the conjunctiva closely examined.
Chemical burns of the eyeball and eyelids should be
continuously irrigated with Ringer lactate or balanced salt
solution for at least 20 minutes, usually under local anesthesia.
CHAPTER REFERENCES
1. Cutarelli PE, Aronsky MA. The painful eye: external and anterior segment causes. Clin Geriatr
Med 1999;15:103112.
2. Verity SM. The combined (genesis) technique of radial keratotomy: a prospective, multicenter
study. Ophthalmology 1995;102:19081917.
3. Mller M, Wessel K, Mehdorn HM, et al. Carotid artery disease in vascular ocular syndrome. J
Clin Neuroophthalmol 1993;13:175180.
4. Ganatra JB, Chandler D, Santos C, et al. Viral causes of the acute retinal necrosis syndrome. Am J
Ophthalmol 2000;129:166172.
5. Selliti TP, Huang AJW, Schiffman J, et al. Association of herpes zoster ophthalmicus with
acquired immunodeficiency syndrome and acute retinal necrosis. Am J Ophthalmol
1993;116:297301.
6. Zimmer-Galler IE, Bartley GB. Orbital emphysema: case reports and review of the literature.
Mayo Clin Proc 1994;69:115121.
7. Holt GR, Holt JE. Incidence of eye injuries in facial fractures: an analysis of 727 cases.
Otolaryngol Head Neck Surg 1983;91:276.
8. Okinaka Y, Hara J, Takahashi M. Orbital blowout fracture with persistent mobility deficit due to
fibrosis of the inferior rectus muscle and perimuscular tissue. Ann Otol Rhinol Laryngol
1999;108:11741176.
9. Iliff N, Manson PN, Katz J, et al. Mechanisms of extraocular muscle injury in orbital fractures.
Plast Reconstr Surg 1999;103:787799.
10. Waterhouse N, Lyne J, Urdang M, et al. An investigation into the mechanism of orbital blowout
fractures. Br J Plast Surg 1999;52:607612.
11. Simon JH, Rubenstein D, Brown M, et al. Quantitative contrast-enhanced MR imaging to the optic
nerve. Acta Radiol 1994;35:526531.
12. Tao H, Ma Z, Dai P, et al. Computer-aided three-dimensional reconstruction and measurement of
the optic canal and intracanalicular structures. Laryngoscope 1999;109:14991502.
13. Blake PY, Mark AS, Kattah J, et al. MR of oculomotor nerve palsy. AJNR Am J Neuroradiol
1995;16:16651672.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

11 ANESTHESIOLOGY
Head & Neck SurgeryOtolaryngology
11




ANESTHESIOLOGY
DIRK YOUNKER
SHAWN D. NEWLANDS

D. Younker: Anesthesia Services, University Hospital, Cincinnati, Ohio.
S.D. Newlands: Department of OtolaryngologyHead and Neck Surgery, University of Texas Medical
Branch, Galveston, Texas.


Local Anesthesia
Local Anesthetic Agents
Nerve Blocks
General Anesthesia
Inhalational Anesthetic Agents
Intravenous Anesthetic Agents
Ancillary Agents
Intravenous Sedative and Hypnotic Agents
Narcotic Agonists and Antagonists
Neuromuscular Blocking Agents and Antagonists
Anesthesia Monitoring
The Anesthesia Machine
Monitors of Oxygenation and Ventilation
Airway Management
Assessing the Airway
Securing the Airway
Anesthetic Considerations for Endoscopic Procedures
Chapter References
Anesthetizing a patient for surgical procedures involving the head and neck is one of the
most challenging aspects of modern anesthesia practice. These patients frequently have
partial upper airway obstruction or impending decompensation. The urgency of the
operation and the stability of the airway direct selection of anesthetic technique,
particularly the maneuvers needed to secure the airway before induction of anesthesia.
Paramount is continuous, thoughtful communication between surgeon and
anesthesiologist. Amnesia, anesthesia, muscle relaxation, airway management, fluid
management, and cardiac and respiratory monitoring all are components of anesthetic
care. Successful surgical and anesthetic care are intertwined. Understanding the basic
principles, physiology, and pharmacology of anesthetic care is crucial to the success of
the otolaryngologist.
Anesthesia can be administered in a number of ways. The major division is general
anesthesia, in which the patient is rendered unconscious, and other techniques, in which
pain is prevented by means of central blocking of conduction of painful stimuli. The
latter techniques involve use of local anesthetic administered by means of infiltration
around the surgical site, peripheral nerves, major nerves, such as the brachial plexus, or
spinal cord (spinal, epidural, or caudal block). Infiltration of major nerves or the spinal
cord rarely is used in head and neck surgery.
LOCAL ANESTHESIA
Local Anesthetic Agents
Local anesthetic agents (Table 11.1) are weak bases that inhibit nerve conduction by
crossing cell membranes and intracellularly blocking electrically excitable sodium
channels. Because the cationic form does not readily cross the cell membrane, tissue
acidosis renders local anesthetic agents ineffective, and the compounds do not produce
anesthesia if injected into abscesses or areas of cellulitis. Local anesthetics tend to be
linear molecules constructed of a hydrocarbon chain separating a lipophilic end from a
hydrophilic end. The lipophilic end contains a benzoic acid moiety, and the hydrophilic
end contains a tertiary or quaternary amine group. They are further subdivided on the
basis of the type of linkage between the benzoic acid moiety and the hydrocarbon chain.
Anilide anesthetics (lidocaine, mepivacaine, bupivacaine, and ropivacaine) contain an
aminoamide linkage, whereas an aminoester bond characterizes ester anesthetics
(cocaine, tetracaine, and benzocaine).

TABLE 11.1. LOCAL ANESTHETIC AGENTS



The type of bond dictates the site of metabolism and route of excretion of both
classifications of local anesthetic. Hepatic microsomal enzyme systems degrade the
anilides into metabolites that possess varying degrees of anesthetic potency. This process
can be profoundly inhibited by cimetidine, which blocks microsomal activity, or by
propranolol, which reduces delivery of the drug to the liver through a decrease in hepatic
blood flow. Plasma cholinesterase metabolizes the aminoester drugs. This process is
much more rapid than hepatic metabolism and can be inhibited by previous
administration of anticholinesterase drugs, such as neostigmine. All local anesthetics
should be used only after the practitioner calculates the safe total dose of the anesthetic
for the patient. This amount of drug can be prepared, and no more anesthetic is given
once this amount is administered.
The aminoamide local anesthetic agents, such as lidocaine, are weak vasodilators that
necessitate the addition of a dilute solution of epinephrine or phenylephrine to aid in
vasoconstriction. Lidocaine is used as both a topical and an injectable local anesthetic.
Four percent solution is most effective for topical use, whereas 0.5% to 1% solution is
effective for injection into soft tissues. To avoid lidocaine toxicity, the recommended safe
dose is 5 mg/kg without epinephrine or phenylephrine and 7 mg/kg with a
vasoconstrictive agent. Dilutions of 1:100,000 or 1:200,000 of epinephrine are commonly
used with injected lidocaine. The lower dose is preferable to minimize the likelihood of
side effects and has efficacy equivalent to that of the higher dose. The total safe dose of
epinephrine in operations on adults is 200 g. Toxic levels of epinephrine cause
hypertension, arrhythmia, and tachycardia. The arrhythmogenic effects of these
catecholamines can be exaggerated by concurrent use of inhaled anesthetics, particularly
halothane, or pancuronium. Mepivacaine has an efficacy and toxicity profile similar to
that of lidocaine but diffuses more readily through tissues and has a longer half-life (1).
The remaining aminoamide local anesthetic agents are less commonly used during
otorhinolaryngologic surgery. Because of its long duration of action, bupivacaine can be
used for nerve blocks or infiltrated into wound closures to provide postoperative pain
relief. The total dose of bupivacaine injected into the soft tissue of the head and neck
should be limited to 3 mg/kg when injected alone and 4 mg/kg when used with
epinephrine. Much lower doses can cause toxicity when administered through the
intravenous, intrapleural, or intrathecal route. Ropivacaine is a newer agent that has
similar efficacy to bupivacaine but is less toxic and produces less motor block for the
same degree of sensory block (2).
Cocaine is unique among the topical anesthetics because in addition to being an excellent
topical anesthetic, it is also a potent vasoconstrictor. For this reason, cocaine can be used
alone in the upper aerodigestive tract for both anesthesia and control of hemorrhage.
Cocaine also is unique because it is highly addictive and is one of the most abused drugs.
For this reason, cocaine use is limited in clinical practice to the mucous membranes of the
head and neck. Studies have failed to substantiate the claim that cocaine is irreplaceable
in otolaryngology. Combinations of lidocaine and epinephrine, phenylephrine, or
oxymetazoline have been shown to be as efficacious as cocaine for a number of purposes
(3), so many otolaryngologists do not use cocaine at all. Cocaine is commonly used as
4% solution for direct application to mucous membranes. The onset of action is quick (5
to 10 minutes), and the duration of action is as long as 6 hours. Cocaine inhibits the
uptake of epinephrine and norepinephrine by adrenergic nerve endings. Therefore it
potentiates the effects of catecholamines. The use of cocaine in conjunction with
epinephrine risks cardiovascular complications that can be fatal. The total dose of cocaine
applied to the mucosa should be limited to 3 mg/kg. Severe or even fatal toxicity from
cocaine can be caused by either central nervous system or cardiovascular effects. Care
should be taken in administering either epinephrine or cocaine to patients with
hypertension, history of arrhythmia, thyrotoxicosis, or coronary artery disease. Tetracaine
is another excellent topical anesthetic agent and is the best topical anesthetic for
ophthalmologic procedures. Although it has 10 times the potency of cocaine, tetracaine
lacks the vasoconstrictor effect of that drug. Benzocaine produces more profound topical
anesthesia than does tetracaine and does so with less toxicity. This drug often is used for
topical application to the upper aerodigestive tract.
Nerve Blocks
Local anesthetic techniques are used in otolaryngology in situations, such as cosmetic
facial surgery, in which distortion of the tissue is undesirable. For this reason, using
smaller volumes of local anesthetic while accomplishing analgesia is the goal. Infiltration
of local anesthetic around the peripheral nerve that supplies the surgical field with
sensation often is desired. Sensory innervation of the head and neck is primarily from the
trigeminal system and the cervical plexus. Effective blockade of sensory branches from
these systems necessitates thorough understanding of the anatomic features of the head
and neck (4). The technique involves use of a 25-gauge needle to infiltrate lidocaine or
bupivacaine around sensory nerve branches as they exit the facial skeleton. Care must be
taken to avoid direct intravascular injection because unintentional injection of local
anesthetic into the vertebral or carotid artery can precipitate a seizure. The practitioner
always should withdraw the plunger before injection of local anesthetic. Careful use of
this technique rarely causes complications.
Procedures on the face performed with local anesthesia are begun after branches of the
fifth cranial nerve are blocked. Blocking the supraorbital and supratrochlear nerves with
1 to 3 mL local anesthetic produces anesthesia of the forehead. The supraorbital nerve is
found exiting the orbit in line with the pupil through the supraorbital notch, which often
can be palpated. The supratrochlear nerve is about 1 cm more medial. Anesthesia of the
external nose necessitates blocking the bilateral anterior ethmoidal nerves and
infratrochlear nerves. This is accomplished with either transcutaneous or submucosal
injection at the junction of the upper lateral cartilage and the nasal bones laterally that is
extended superiorly between the medial canthus and the nasal dorsum.
The maxillary nerve (V2) can be blocked in the pterygopalatine fossa with either a
transoral approach or a transcutaneous approach beginning at the coronoid notch and
traversing the infratemporal fossa. This block anesthetizes the maxilla, palate, maxillary
dentition, and the skin and mucosa of the midface. This block is not in common use;
procedures that necessitate such extensive anesthesia of the midface are more often
performed with general anesthesia. Blockade of the major terminal branches of the
maxillary nerve is more commonly used.
Infraorbital nerve block anesthetizes the maxillary incisors, cuspids and bicuspids,
associated gingiva, the lower eyelid, anterior cheek, and the upper lip. Less than 3 mL of
solution is needed. The nerve is reached with either an external or a sublabial approach.
The nerve is in line with the pupil and about 1 cm below the infraorbital rim. The palate
can be anesthetized by means of blocking the anterior palatine and nasopalatine nerves as
they emerge from the greater palatine foramen and incisive canal. Small volumes (0.5 to
1 mL) of anesthetic are needed. Care must be taken because injection into bony foramina
can cause pressure-induced or needle-induced nerve injury and permanent paresthesia.
The mandibular branch of the trigeminal nerve can be anesthetized at the skull base as it
leaves the foramen ovale. The needle is placed through the coronoid notch and across the
infratemporal fossa. The injection is made posteriorly to the lateral pterygoid plate.
Blockade of this nerve is used for procedures on the mandible, gingiva, lower teeth,
lower lip, anterior two thirds of the tongue, and floor of the mouth. Most procedures that
necessitate this extent of anesthesia are performed with general anesthesia. Peripheral
nerve blockade is more commonly applied to branches of the mandibular nerve.
The inferior alveolar nerve can be blocked through a transoral approach as the nerve
enters the mandibular foramen in the pterygomandibular space. This technique is
commonly used in oral surgery for work on the lower teeth. The injection is immediately
medial to the mandibular ramus about 1 cm above the occlusal surface of the posterior
molars at the anterior-posterior level of the coronoid notch. With the technique the needle
is superior to the medial pterygoid muscle and immediately medial to the mandibular
sulcus. Use of this approach commonly blocks the lingual nerve, because the lingual
nerve is slightly medial and anterior to the inferior alveolar nerve. Anesthesia of the
buccal mucosa is accomplished by means of blocking the buccal nerve as it passes over
the anterior ramus at the level of the occlusal surface of the molars. Another commonly
blocked branch of cranial nerve V3 is the mental nerve. This blockade is accomplished
with injection at the mental foramen between the two bicuspids at a level immediately
below the tooth root apices. The approach can be intraoral or extraoral. In edentulous
patients, the location of the foramen can be found by remembering that it is in line with
the pupil. This technique anesthetizes the lower lip, gingiva, and teeth from the bicuspids
to the midline.
Anesthesia of the neck, inferior and posterior auricle, and scalp can be accomplished by
means of blockade of the cervical plexus. The cervical plexus arises from the C2, C3, and
C4 spinal nerves. These spinal nerves can be blocked as they emerge from the foramina
in the cervical vertebrae with an approach lateral to the sternocleidomastoid muscle. This
blockade must be done with care to avoid injection into the vertebral artery, and spread to
involve the phrenic nerve is likely. This technique can be useful in complex surgical
procedures on cervical structures, but these procedures usually are performed with
general anesthesia. An alternative is to block the cutaneous innervation from the cervical
plexus more safely by means of injection of up to 10 mL of local anesthetic at the
posterior border of the midpoint of the sternocleidomastoid muscle (Erb point).
Blockade of the superior laryngeal nerve can be attained by means of infiltration of local
anesthetic where the nerve enters the thyrohyoid membrane immediately inferior to the
lesser cornu of the hyoid bone. This technique is used to facilitate endoscopic procedures
performed with local anesthesia and is used to allow endoscopic intubation of patients for
whom topical anesthesia is difficult.
GENERAL ANESTHESIA
The unifying characteristic of general anesthetic agents is the ability to render a patient
unconscious and insensible to painful surgical stimuli. They differ widely in amnestic and
analgesic properties, in muscle relaxant characteristics, and in efficacy in the control of
unwanted autonomic reflexes. Although local anesthetics have some of these other
properties, some newer inhalational agents provide unconsciousness, amnesia, analgesia,
and autonomic reflex control without the aid of adjuvant drugs. The variety of anesthetic
agents enables the anesthesiologist to tailor care to the demands of different surgical
procedures.
Inhalational Anesthetic Agents
The characteristics of some inhalational anesthetic agents are given in Table 11.2.
Halothane is the best known of the halogenated inhalational anesthetics. These agents
exist as liquids at ambient temperature and pressure, and they are easily transformed into
gas for rapid absorption and elimination by the pulmonary circulation.

TABLE 11.2. INHALATIONAL ANESTHETIC
AGENTS



Halothane is a volatile, nonflammable, alkane anesthetic. It is sufficiently potent to be
administered as the single anesthetic agent in a high inspired oxygen concentration. Its
potency, pleasant smell, and lack of bronchoirritant effects make it useful in operations
on patients, particularly small children, who need inhalation induction (straight
induction). Because halothane possesses minimal respiratory depressant effects on
patients who have not received premedication, the drug is quite useful if it is necessary to
anesthetize a patient for airway manipulation without producing apnea or loss of
pharyngeal muscle tone.
Halothane is highly soluble in blood and fatty tissue. Awakening from halothane
anesthesia can be prolonged if careful attention is not given to the timing of emergence.
Halothane has a depressant effect on cardiac muscle contractility and on intrinsic cardiac
conducting tissue. Large doses of halothane can produce bradycardia and hypotension
from primary myocardial depression. The drug sensitizes the myocardium to the effects
of circulating catecholamines. Hypercarbia from inadequate ventilation and high
epinephrine levels from absorption of locally applied epinephrine or cocaine can cause
severe ventricular ectopia during halothane anesthesia.
About 12% of an absorbed halothane dose is metabolized into various halogenated by-
products, which are excreted in the urine. Some of these reductive metabolites produce
postoperative hepatic inflammation (halothane hepatitis) among patients with hepatic
anoxia from profound hypotension or arterial hypoxemia. Although this complication is
severe, it is extremely rare and confined almost exclusively to adults. To avoid this
complication, many anesthesiologists avoid the use of halothane in the care of patients at
risk of intraoperative circulatory instability or adults who have had previous exposure to
halothane.
Halothane is a triggering agent for malignant hyperthermia, a well-known anesthetic
reaction usually detected among pediatric patients during a first halothane anesthesia.
Malignant hyperthermia occurs more commonly if succinylcholine has been used for
muscle relaxation. Characteristics of malignant hyperthermia include masseter spasm,
sustained muscle rigidity, myoglobinuria, and a rapidly increasing core body temperature.
These are manifestations of a generalized hypermetabolic state initiated by halothane-
triggered inhibition of calcium reuptake into the sarcoplasmic reticulum of skeletal
muscle. If not controlled swiftly and appropriately, malignant hyperthermia is fatal. The
principles of management include support of oxygenation and ventilation, total-body
cooling, vigorous hydration, and intravenous administration of dantrolene sodium in an
initial dose of approximately 10 mg per kilogram of body weight. These patients can be
anesthetized safely for subsequent procedures if the appropriate preventive measures are
instituted.
Other halogenated inhalational agents have been developed to address some of the
shortcomings of halothane. Enflurane and isoflurane are short-chain-hydrocarbon volatile
anesthetics that contain an ether linkage. They are isomers of one another and are
halogenated with chlorine and fluorine. They are not flammable and are sufficiently
potent to be administered as the sole anesthetic agent in a high inspired oxygen
concentration. They possess distinctive, pungent odors that cause unpleasant inhalation
induction when the patient has not undergone premedication. These drugs produce more
intrinsic respiratory depression than does halothane, but they tend to have less of a
depressant effect on the myocardium. Hypotension with the use of these agents is caused
primarily by peripheral vasodilatation. Unlike halothane, these drugs are less soluble in
blood and fatty tissue, producing a more rapid emergence from general anesthesia.
Arrhythmia due to elevated levels of circulating catecholamines is less likely than with
halothane. Enflurane is rarely used because of the risk of renal toxicity and seizure.
Sevoflurane and desflurane are nonflammable, volatile, halogenated agents that are
completely fluorinated analogues of isoflurane. Because of low lipid solubility, both
agents produce rapid awakening from general anesthesia without the use of nitrous oxide
and both cause little myocardial depression. Although preferred for quick awakening,
sevoflurane and desflurane are used less than isoflurane because of expense. Although
sevoflurane is gentle on the airway, desflurane is a pungent agent with pronounced
bronchoirritative properties.
Nitrous oxide is noteworthy for its lack of solubility in body tissues. It is not a potent
inhalational anesthetic, and brain concentration sufficient to render a patient unconscious
may not be achieved at atmospheric pressures. Nitrous oxide is most commonly used in
an inspired gas mixture consisting of oxygen and a potent halogenated volatile anesthetic.
In this combination, nitrous oxide speeds induction and emergence from general
anesthesia and enhances the intrinsic analgesic properties of the chosen halogenated
anesthetic. Nitrous oxide can support combustion, especially if delivered with a high
concentration of oxygen. This characteristic is particularly important in procedures that
entail laser endoscopy. Nitrous oxide quickly diffuses into closed, air-filled body cavities
to produce a rapid expansion of volume. Its use must be avoided in the presence of
obstructive ileus, pulmonary bullae, or an unrelieved pneumothorax. The middle ear
represents an anatomic air cavity vented to the atmosphere only when the eustachian tube
is open. If high concentrations of nitrous oxide are used in the inspired gas mixture, the
nitrous oxide diffuses into the middle ear faster than nitrogen is able to diffuse out. The
result is an increase in intracavitary pressure that can be great enough to rupture the
tympanic membrane or to dislodge a graft during otologic surgery. To avoid this, it is
common practice to limit the concentration of nitrous oxide to 50% and to stop
administration 15 minutes before graft placement. Nitrous oxide undergoes minimal
metabolism by the liver; however, prolonged exposure to high concentrations inhibits
methionine synthetase activity and can cause megaloblastic or aplastic anemia.
The use of potent inhalational agents for maintenance of anesthesia offers advantages in
head and neck patients. First, they can decrease bronchoconstriction by means of relaxing
bronchial smooth muscle. Second, potent inhalational agents allow administration of high
inspired oxygen concentrations. Third, they produce a stable level of muscle relaxation
without the use of neuromuscular blocking drugs, allowing assessment of facial nerve
function. Fourth, induction with these agents of moderate degrees of hypotension in
concert with a 15-degree head-up tilt can reduce surgical blood loss. Fifth, rapid
elimination through the lungs allows prompt return of protective airway reflexes among
patients who have not undergone tracheostomy.
Intravenous Anesthetic Agents
Intravenous anesthetic agents can render a patient unconscious, but they usually
necessitate administration of additional drugs to produce reliable amnesia, analgesia, and
muscle relaxation. The rapidity of onset is determined to a great extent by the time it
takes for one of these drugs to reach a critical brain concentration from its point of
injection (arm-brain circulation time). The duration of activity is somewhat variable and
is governed by the capacity of the hepatorenal system for metabolism and excretion.
For most surgical procedures, the first step in production of general anesthesia is
intravenous administration of a hypnotic drug, followed by maintenance of anesthesia
with an inhalational agent or nitrous oxide supplemented with narcotics. This intravenous
induction usually is more acceptable to the patient than inhalation induction with a
pungent volatile agent. The drugs commonly used for this purpose share the ability to
produce a state of unconsciousness rapidly, which coincides with a critical peak
concentration in brain tissue (5). Awakening occurs when this concentration decreases,
usually through redistribution of the drug from brain tissue to adipose tissue. Metabolism
and excretion of the drug then take place in the liver and other organs (Table 11.3).

TABLE 11.3. INTRAVENOUS ANESTHETIC
AGENTS



Barbiturates are lipid-soluble, highly alkalotic compounds, the central ring structure of
which consists of a fusion of urea and malonic acid. The two subgroups, thiobarbiturates,
such as pentobarbital, and oxybarbiturates, such as methohexital, are differentiated by a
sulfur or oxygen molecule attached to the urea moiety. The drugs of this family generally
produce unconsciousness within 3 minutes of intravenous administration, and awakening
usually occurs within 10 minutes of initial dosage. Hypotension after induction with
barbiturates usually is caused by vasodilatation in a patient with hypovolemia, possibly as
the result of massive histamine release. Barbiturates are primary respiratory depressants
that produce apnea at the doses normally given for induction of anesthesia. Accordingly,
equipment for airway maintenance should be immediately available when a barbiturate is
given. Barbiturates, like any other respiratory depressant, should be administered with
caution if the airway is likely to be difficult to maintain in the absence of spontaneous
ventilatory effort.
Etomidate is an imidazole intravenous anesthetic agent structurally related to the
antifungal drug, ketoconazole. It produces minimal derangement of cardiovascular
function, so it is preferred to barbiturates in operations on patients in hemodynamically
unstable condition. Etomidate usually does not produce apnea if premedication has not
been administered, but rapid administration can produce impressive myoclonus, which is
of no clinical significance. Etomidate is formulated in a solvent containing propylene
glycol, which produces pain and phlebitis during intravenous injection. The venoirritation
and myoclonus can be ameliorated with administration of sedatives or narcotics before
the injection. Classic addisonian crises have been reported after prolonged infusion of
etomidate for sedation of patients who have undergone long-term intubation.
Propofol is a substituted phenol with a rapid onset and short duration of action.
Awakening after a dose of propofol is effortless, and there is little residual sedation.
Propofol does not appear to produce respiratory depression among healthy persons who
have not received premedication. Pronounced hypotension caused by peripheral
vasodilatation can occur after use of propofol in operations on patient with hypovolemia
or in debilitated condition. Propofol is formulated in a soybean emulsion. This solvent
causes venoirritation and phlebitis after intravenous administration of the drug. The brief
duration of activity of propofol allows patients to return quickly to preoperative levels of
mental alertness. Propofol is therefore popular for induction and maintenance of
anesthesia for brief outpatient procedures, but the expense prohibits widespread use.
Ketamine is a cyclohexanone derivative similar in structure and activity to the
hallucinogen phencyclidine. Its mode of action in producing a state of anesthesia is
unique. Ketamine appears to interrupt at a cortical level the perception of pain. A patient
who has received an induction dose of ketamine appears to be conscious but neither
responds to nor has memory of painful stimuli. This is described as the dissociative effect
of ketamine. Even in small doses, the drug produces intense analgesia, anterograde and
retrograde amnesia, and support of the blood pressure by the release of endogenous
catecholamines. It does not produce respiratory depression among healthy persons who
have not received premedication. Ketamine enhances the production of oral secretions
and increases the likelihood of laryngospasm. Emergence from ketamine anesthesia can
appear smooth, but because many patients have hallucinations in the recovery period, this
drug is not widely used in operations on adults.
ANCILLARY AGENTS
Intravenous Sedative and Hypnotic Agents
Drugs used to produce sedation and hypnosis belong almost exclusively to the categories
of major or minor tranquilizers. They are commonly administered as premedicants to
reduce preoperative anxiety. They are essential for the comfort of patients undergoing
regional anesthesia. Benzodiazepines are one of the most useful drug families in
anesthesiology. The mode of action appears to be enhancement of the effects of the
inhibitory neurotransmitter, -aminobutyric acid (6). In low doses, benzodiazepines
produce reliable anxiolysis, sedation, and amnesia. In the higher doses necessary for
induction of general anesthesia, these drugs can prolong the emergence phase with
marked residual drowsiness. Benzodiazepines tend to preserve hemodynamic stability if
administered to healthy persons who have not received premedication. Patients in
debilitated condition or who have hypovolemia sometimes have profound hypotension,
especially if narcotics also are given. Benzodiazepines blunt the central ventilatory
response to hypercarbia and can produce abrupt respiratory depression, even without
concomitant administration of a narcotic. Benzodiazepines should be administered with
care to patients with respiratory insufficiency.
Diazepam, the prototype benzodiazepine compound, has a long history of safety and
efficacy. However, it has yielded its position of prominence to midazolam. Midazolam is
about three times as potent as diazepam, and the duration of activity is much shorter.
More rapid termination of the effect of midazolam is caused by its almost total
metabolism by hepatic microsomal enzyme systems. Midazolam is water soluble, and it
does not produce venous irritation after intravenous injection. The specific
benzodiazepine antagonist, flumazenil, is helpful in relieving the prolonged sedation that
benzodiazepines occasionally produce (7).
Narcotic Agonists and Antagonists
Narcotic agonists are a cornerstone of current anesthesia practice. In addition to
immediate usefulness in providing perioperative analgesia, narcotic agonists often are
used intraoperatively as a component of intravenous anesthetic technique. Although the
narcotics available today differ widely in chemical structure, they share an ability to bind
to specific opiate receptor sites in the brain and spinal cord. It is the binding to these
receptors that produces analgesia and the well-known narcotic side effects of meiosis,
respiratory depression, constipation, and urinary retention (8).
Morphine, a naturally occurring opium derivative, has been used for centuries as an
analgesic and antidiarrheal agent. Morphine is fairly insoluble in lipids and is effective
given by the intramuscular, intravenous, epidural, or intrathecal route. It is inexpensive
and possesses a fairly long duration of action. Smaller doses of morphine can be used for
premedication, postoperative pain control, and as an adjuvant in nitrous oxide and
narcotic relaxant techniques. Larger doses of morphine are used almost exclusively in
anesthesia for cardiovascular procedures. The respiratory depressant effects of morphine
are well known. Even a small dose can produce abrupt apnea among elderly or debilitated
patients. Histamine release can cause profound hypotension among patients with
hypovolemia. Morphine has hepatic and renal pathways of metabolism and is excreted
into the bile and the urine.
Use of the potent, synthetic narcotics alfentanil, sufentanil, and, primarily, fentanyl is
restricted to the operating room, where equipment for ventilatory support is readily
available. These drugs contain a piperidine ring and are noteworthy for the production of
rapid, intense analgesia. Abrupt, profound respiratory depression can occur with the onset
of analgesia. Fentanyl and sufentanil are quite lipid soluble and have a rapid onset of
action. They can maintain cardiovascular stability even in large doses. They are
metabolized by hepatic microsomal systems and are excreted into the urine. Alfentanil is
fairly insoluble in fatty tissues. The volume of distribution is much smaller than that of
fentanyl or sufentanil, and much more of the drug is immediately available for hepatic
degradation. This causes duration of activity far shorter than obtained with either of the
other two piperidine opioids. Profound hypotension and bradycardia can occur even
among healthy persons after rapid intravenous administration of alfentanil. Alfentanil
should be given carefully to patients in hemodynamically unstable condition.
Remifentanil is a new opioid within the piperidine series of narcotics. It is metabolized
by nonspecific plasma esterases. Rapid awakening with little drug hangover and no
residual analgesia are hallmarks of this drug. Because of cost constraints and because
rapid shutoff of analgesia is undesirable in most surgical settings, use of remifentanil
often is limited to short endoscopic procedures and to neurosurgical procedures in which
immediate postoperative, neurologic assessment is indicated.
Naloxone can be used to antagonize the residual respiratory depression or other unwanted
side effects that can occur after the use of an opioid substance (9). Caution must be
observed in achieving this goal, however, if large doses of a narcotic have been given as
part of a nitrous oxide and narcotic relaxant technique, particularly in the case of the
piperidine compounds alfentanil, fentanyl, and sufentanil. In this clinical situation, the
effects of naloxone can dissipate before metabolism of the narcotic is complete, and
precipitous respiratory depression can occur.
Butorphanol, nalbuphine, and buprenorphine are drugs with mixed opiate agonist and
antagonist properties. The theoretic advantage over pure narcotic agonists is production
of analgesia without respiratory depression, although these drugs are less commonly used
than pure narcotic agonists.
Neuromuscular Blocking Agents and Antagonists
Muscle relaxants claim a critical role in modern anesthesia practice (Table 11.4). They
facilitate endotracheal intubation and enhance the intrinsic muscle-relaxant properties of
many inhalational agents. In otolaryngologic surgery, management of muscle relaxation
can be particularly difficult. Periodic assessment of the integrity of the facial nerve is
essential for the success of many types of surgery involving the ear or parotid gland.
Eliciting a facial grimace by means of direct electrical stimulation of the nerve is the
easiest method of identification. This is facilitated with judicious use of muscle relaxants
and the guidance of a twitch monitor to ensure maintenance of an easily reversible degree
of muscle paralysis. An alternative approach is the use of a potent inhalational agent to
produce a deep plane of general anesthesia. With this technique, facial nerve function can
be fully preserved, and moderate degrees of hypotension can be induced when necessary.

TABLE 11.4. NEUROMUSCULAR BLOCKING
DRUGS



The two major categories of relaxant drugs are competitive and noncompetitive inhibitors
of neuromuscular transmission. The common site of activity is the postsynaptic
membrane of the nicotinic cholinergic receptor. Competitive blocking agents
(nondepolarizing drugs) bind loosely to the receptor site and possibly by acetylcholine in
a concentration-dependent manner. Noncompetitive blocking agents (depolarizing drugs)
bind strongly to the receptor site and mimic the electrophysiologic effect of acetylcholine
at the endplate, depolarizing the membrane and rendering it incapable of further
stimulation.
Succinylcholine is the most commonly used depolarizing neuromuscular blocking drug.
It is similar in structure to acetylcholine and imitates the effects of this agent at the motor
endplate. Muscle fasciculation heralds the onset of succinylcholine-induced paralysis
unless specific measures are taken to block it. The drug has a rapid onset of action and a
short duration of activity owing to rapid metabolism by plasma cholinesterases. This
pharmacokinetic profile makes this drug useful in induction of anesthesia and in
intubation for procedures in which muscle paralysis is not desired (parotidectomy).
Succinylcholine can be given by means of intermittent bolus or continuous infusion.
Prolonged paralysis can occur if excessive doses are administered by either route.
Succinylcholine can produce profound bradycardia mediated by stimulation of cardiac
muscarinic receptors. Pretreatment with a small dose of atropine or glycopyrrolate blocks
this phenomenon. Potassium efflux from the intracellular fluid is the unavoidable
consequence of succinylcholine action. The average elevation of potassium concentration
in the serum after a dose of succinylcholine is 0.5 to 1.0 mEq/L. For healthy persons with
a normal preoperative potassium level, this is of no physiologic significance; however,
life-threatening hyperkalemia can develop among patients with massive crush injuries,
burns, paraparesis, or renal failure. In these situations, succinylcholine must be given
cautiously or not at all.
The nondepolarizing drug tubocurarine (curare) is the prototype of the benzylisoquinoline
competitive neuromuscular blocking agents. Other members include metocurine,
atracurium, mivacurium, and cisatracurium, which is the most useful. Curare itself is used
primarily to block the fasciculation produced by succinylcholine administration, but
profound histamine-induced hypotension can occur after rapid intravenous injection of
curare. Although similar in structure to curare, each of the other drugs in this
classification represents the product of continual research to increase the potency,
decrease the duration, and reduce the number of side effects associated with the use of
tubocurarine.
Pancuronium, vecuronium, rocuronium, and rapacuronium are competitive,
nondepolarizing muscle relaxants that each contain a steroid nucleus. Pancuronium is
about six times more potent than curare, and it has duration of activity of approximately
90 minutes. It is degraded in the liver into fairly potent active metabolites and is excreted
primarily by the kidneys. Pancuronium produces a marked increase in heart rate after
intravenous administration, in part because of its strong anticholinergic activity at the
cardiac muscarinic receptors and in part because of its ability to block norepinephrine
reuptake into presynaptic nerve terminals. These properties of pancuronium can cause
surprising atrial and ventricular tachydysrhythmia if the drug is given in combination
with halothane, cocaine, or epinephrine-containing local anesthetic solutions.
Rapacuronium is preferred for its rapid onset (less than 2 minutes), short duration of
action (10 to 16 minutes), and lack of cardiac side effects (10).
Examples of anticholinesterase agents frequently used to terminate the effects of muscle
relaxants include neostigmine and edrophonium. Each agent contains a quaternary
ammonium group that renders the drug poorly soluble in body lipids. Edrophonium binds
loosely and reversibly to acetylcholinesterase through a combination of electrostatic and
hydrogen bonding to produce a rapid onset of action and a short duration of activity.
Neostigmine, however, binds more tightly to acetylcholinesterase. The result is a longer
onset of action and longer duration of activity. Anticholinesterase agents block the
activity of plasma cholinesterase and prolong the paralysis produced by succinylcholine.
Administration of an inhibitor of acetylcholinesterase increases the amount of
acetylcholine available for binding to the postsynaptic nicotinic receptors of the
neuromuscular junction and to the muscarinic receptors in the parasympathetic ganglia.
Stimulation of these muscarinic receptors produces bradycardia, salivation,
bronchoconstriction, and an increase in gastrointestinal motility. These unwanted side
effects can be blocked by the properly timed administration of an anticholinergic drug,
such as atropine or glycopyrrolate. Drug pairs are selected with an effort to match
respective time of onset and duration of activity. Atropine frequently complements
edrophonium, and glycopyrrolate commonly accompanies neostigmine.
ANESTHESIA MONITORING
Technical improvements in anesthesia machines and in the noninvasive monitoring of
oxygenation and ventilation allow successful administration of anesthesia to patients who
not long ago were considered too ill for surgery. Alarm systems that announce anesthesia
circuit disconnection or warn of a hypoxic inspired gas mixture are standard features on
most modern anesthesia machines. Tissue oxygenation can be assessed continuously with
the noninvasive technique of pulse oximetry, and ventilation can be monitored with real-
time capnography.
The Anesthesia Machine
When reduced to its bare essentials, the anesthesia machine consists of oxygen and
anesthetic vapor delivery systems, a reservoir bag or ventilator used to assist patient
ventilation, and a circuit that provides a conduit through which anesthetic gases or
oxygen reach the patient (11). Oxygen flows to the patient from a wall source or an
oxygen tank attached to the anesthesia machine. The rate of administration is controlled
with precisely calibrated flowmeters. Nitrous oxide, carbon dioxide, and air can be given
in a similar manner. Inhalational anesthetic agents can be added to the inspired mixture
by allowing this carrier gas to flow over and to evaporate a pool of liquid anesthetic
contained in an agent-specific vaporizer. The vaporizer accurately controls the amount of
anesthetic vapor allowed to saturate the carrier gas and directly regulates the
concentration of anesthetic entering the patient. The anesthesiologist adjusts the depth of
anesthesia by increasing or decreasing the amount of anesthetic vapor introduced into the
delivery system. As the depth of anesthesia increases, a reservoir bag or an automatic
ventilator is used to assist or to control the patient's breathing.
An anesthesia breathing circuit makes the final connection between the machine and the
patient. The inspiratory limb of a breathing circuit conducts each anesthetic-laden,
oxygen-enriched breath from the machine to the patient. The expiratory limb of the
circuit routes expired gas containing carbon dioxide through an adjustable relief valve to
an exhaust system. One-way valves and an internal carbon dioxide absorber prevent
rebreathing by the patient of any carbon dioxideladen gas not vented into the exhaust
system. An oxygen monitor with electronic alarm capability is in the inspiratory limb of
the breathing circuit to detect any deviation of the oxygen concentration from preset
limits. This monitor represents the first step in a series of interconnected safety
mechanisms designed to prevent the catastrophic administration of a hypoxic gas mixture
to the patient. Other links in this safety chain include alarms that activate when the
oxygen line pressure is low and a cutoff valve that terminates nitrous oxide flow when
oxygen line pressure begins to decrease.
Monitors of Oxygenation and Ventilation
Continuous, noninvasive measurement of hemoglobin saturation is possible with pulse
oximetry (12). The concept is based on the fact that oxyhemoglobin and reduced
hemoglobin absorb different wavelengths of light. A light-emitting diode is placed on a
fingertip and shines light of two wavelengths, such as 660 nm and 940 nm, through the
tissue. The ratio of the absorbance spectra of these two wavelengths is calculated and
expressed as percentage oxygen saturation. The oximetry unit does not directly measure
PaO
2
, and the pulse oximeter continuously displays a saturation of at least 98% through a
range of PaO
2
values between 150 and 550 mm Hg. Because it does not indicate a drop in
arterial saturation until PaO
2
decreases to less than 100 mm Hg, a pulse oximeter is not
useful for detecting a downward trend in arterial oxygen tension until PaO
2
decreases to
less than this level. The shape of the oxygen-hemoglobin dissociation curve causes this
phenomenon.
Although this monitoring modality reliably detects arterial desaturation for most patients,
there are limitations to the use of pulse oximetry. Ambient light or the injection of
biologic dyes such as methylene blue can artificially decrease the hemoglobin saturation
displayed. Electrocautery or patient movement can cause mechanical interference with
signal processing. Vasoconstriction initiated by hypovolemia, hypothermia, or
hypotension can be so intense that the oximeter cannot detect pulsatile flow and cannot
determine a saturation value.
The adequacy of ventilation can be monitored continuously with capnography, a method
of detecting the amount of carbon dioxide in expired gas. The actual measurement can be
obtained with two different toolsan infrared analyzer or a mass spectrometer. Infrared
analysis is more readily available and is based on the fact that carbon dioxide absorbs
infrared light at specific wavelengths (2,600 and 4,300 nm). Modern mass spectometry
units are compact, give nearly instantaneous feedback, and have the advantage of
analyzing the concentration of oxygen, nitrogen, carbon dioxide, and inhalational agents
in the expired gas. They are, however, more expensive than infrared devices.
In anesthesia, capnography is most useful in monitoring and adjusting patient ventilation.
It also is helpful in two other clinical situations. The absence of carbon dioxide in the
expired gas of a patient after attempted intubation can indicate that the endotracheal tube
is incorrectly positioned (13). A rapid decrease in the baseline value of expired carbon
dioxide can be caused by a decrease in the amount of blood entering the pulmonary
circulation, a circumstance that can occur after intraoperative hypovolemia, pulmonary
thromboembolism, or a gas embolism.
AIRWAY MANAGEMENT
Assessing the Airway
Careful preoperative airway assessment is essential for the safe induction of anesthesia
for a patient scheduled for surgery. Difficulty in managing the airway is the single most
important cause of anesthesia-related morbidity and mortality. Successful management of
a difficult airway begins with recognition. The first step is acquisition of a thorough
history with special reference to symptoms that suggest airway abnormalities, including
hoarseness, dyspnea, orthopnea, dysphagia, or a history of previous head or neck disease.
A history of previous airway difficulties with intubation should be explored, and any
available anesthesia records from previous intubations must be reviewed. During the
preoperative physical examination, a small, receding chin; large, protruding teeth; bull
neck; highly arched palate; or a distance of less than 6 cm between the lower border of
the mandible and the thyroid notch all indicate possibility of difficult intubation (14). To
assess temporomandibular joint mobility and the adequacy of the oral cavity, the patient
should be asked to open his or her mouth as widely as possible and to extend the tongue
fully. At the same time, the mouth should be examined for loose teeth, prostheses, or an
unsuspected mass (15). The patient's ability to assume the sniff position is assessed.
Ventilation or intubation of patients with some congenital anomalies can be impossible if
apnea occurs. These syndromes include Beckwith-Wiedemann, Crouzon, Down,
Goldenhar, Pierre Robin, Treacher Collins, and Turner syndromes, congenital rubella,
and mucopolysaccharidosis. The airway may be impossible to manage because of the
underlying pathologic condition, such as head and neck cancer, obstructive sleep apnea,
or facial trauma. Long-standing rheumatoid arthritis can cause atlantooccipital
subluxation and extreme laryngeal deviation. Patients who have intrathoracic tracheal
compression from extensive mediastinal adenopathy, retrosternal goiter, or massive
neoplasia in the anterior mediastinum can be easy to perform intubation but impossible to
ventilate if the mass obstructs the trachea after loss of spontaneous respiration.
Thorough study of an airway found to be abnormal before surgery can prevent
catastrophe during induction of anesthesia. Flow-volume loops are helpful in assessing
the degree of tracheal obstruction caused by large cervical or intrathoracic masses.
Fiberoptic laryngoscopy or tracheobronchoscopy performed with topical anesthesia with
the patient awake and spontaneously breathing can be invaluable in evaluation of a
patient who has grossly distorted anatomic landmarks.
Securing the Airway
After completion of additional diagnostic studies, a plan can be constructed for inducing
anesthesia and securing the airway. If there is no suspicion of a difficult airway, routine
intubation is performed. If it seems as if the airway will be difficult to manage, the airway
must be secured with the patient awake. This can be accomplished by means of direct
laryngoscopy and intubation performed with topical anesthesia while the patient is
spontaneously breathing and with fiberoptic intubation, retrograde intubation, or
tracheostomy with local anesthesia (15,16). In many cases, the surgeon has evaluated the
pathologic condition that makes the airway abnormal. Patients scheduled for
laryngectomy may have undergone radiation therapy to the head and neck that caused
epiglottic fibrosis, laryngeal edema, or trismus. Partial airway obstruction from laryngeal
or oropharyngeal masses may already exist and necessitates careful planning of
intubation techniques. Communication between the anesthetist and otolaryngologist
before the patient reaches the operating room is crucial.
An array of equipment is designed to assist in the insertion of endotracheal tubes. Most
commonly used is the handheld halogen bulb laryngoscope. It is a left-handed instrument
fitted with a straight, low-flange blade (Magill) or a curved blade (McIntosh). These
blades are made in a full range of sizes for adult and pediatric patients. Both are inserted
into the right side of the mouth and are lifted at a 45-degree angle to the oropharyngeal
axis to move the tongue into the mandibular space. For exposure of the vocal cords, the
tip of the straight blade rests under the epiglottis, and the tip of the curved blade rests in
the vallecula. Various maneuvers, such as application of cricoid pressure or the use of an
endotracheal tube director, can be used in difficult cases to visualize the vocal cords. If
the anesthetist is unable to perform intubation because of an unanticipated difficult
airway, the patient should be awakened and difficult airway intubation techniques used.
In the event of failed laryngoscopy or intubation or precipitous airway obstruction,
manual ventilation with mask and reservoir bag can be effective in oxygenating and
ventilating the patient. If manual ventilation is not effective and a second laryngoscopy is
not successful, an artificial airway should be established. This can take the form of
cricothyrotomy or tracheostomy (14).
If an airway is difficult to manage, conventional intubation can be performed with the
patient lightly sedated and topically anesthetized but spontaneously breathing to protect
against loss of the airway. An alternative is to use a flexible fiberoptic laryngoscope or a
pediatric bronchoscope, after topical anesthesia of the oropharynx and adequate sedation,
to direct an adult-sized endotracheal tube between the vocal cord of a conscious,
spontaneously breathing patient. Smaller flexible fiberoptic bronchoscopes exist that
allow passage of pediatric or neonatal endotracheal tubes. This technique is the most
widely used of the second-line intubation techniques.
There are disadvantages to the use of flexible fiberoptic laryngoscopy or bronchoscopy
for endotracheal intubation. Successful fiberoptic intubation is directly related to the skill
of the operator of the bronchoscope. Disrupted or severely abnormal anatomic features
can preclude successful navigation of the airway by all but the most expert endoscopists.
Patient cooperation also is critical to fiberoptic intubation. For fiberoptic laryngoscopy to
be effective in securing the airway, patients must be carefully selected and prepared for
the procedure.
There are many other difficult airway techniques in the armamentarium of a well-trained
anesthesiologist. Those techniques include blind intubation, use of a light wand, and
retrograde intubation. If intubation fails, ventilation can be maintained with a laryngeal
mask airway or transtracheal jet ventilation. Oral and nasopharyngeal airways are useful
in the care of patients with obstruction at the level of the oral cavity and oropharynx
respectively. The otolaryngologist often can use a rigid ventilating bronchoscope to
secure the difficult airway in an emergency. Most anesthesiologists are skilled in several
but not all of the techniques of management of a difficult airway and should use the
techniques that work well for them. The anesthetist must be prepared to use several of
these techniques because any one may fail.
In situations such as tracheotomy for postoperative airway management in the care of
patients with head and neck cancer, the safest way to establish an airway often is to
perform tracheotomy with local anesthesia and the patient awake. Other circumstances
include laryngeal fracture, airway abscess, and fracture of the base of the skull that
prevents use of nasal intubation in the care of patients who need maxillomandibular
fixation. Patients with disease so severe as to necessitate awake tracheotomy often cannot
tolerate lying supine, so the tracheotomy is performed with the patient sitting upright.
Awake tracheotomy demands teamwork between the patient, nursing staff,
anesthesiologist, and surgeon.
Formal tracheostomy under emergency conditions is a procedure best performed by an
experienced surgeon; however, life-saving cricothyrotomy can be performed rapidly with
minimal training with equipment readily found in the operating room. A 12- or 14-gauge
intravenous cannula is inserted through the cricoid membrane into the trachea below the
point of upper airway obstruction. The external end of the cannula is attached to a 3-mL
syringe with the plunger removed. The adapter from a 7.0- or 8.0-mm endotracheal tube
is pushed into the barrel of the syringe, and the cricothyrotomy unit is connected to the
anesthesia circuit in the usual manner. Ventilation of the patient is instituted through the
cannula by means of manual compression of the reservoir bag of the anesthesia circuit.
The internal diameter of the cannula is small, and passive expiration occurs mainly
through the obstructed airway rather than the cannula. Sufficient time must be allowed
for the appropriate inspiratory and expiratory phases of ventilation to avoid gas trapping
or inadequate ventilation. Adequacy of gas exchange is best judged with close
observation of chest excursion and pulse oximetry. This cricothyrotomy apparatus can be
quickly modified to allow connection of a jet ventilator for more effective ventilation of
the lungs. It is imperative that the surgeon be present during intubation of difficult
airways to assist with emergency airway management.
ANESTHETIC CONSIDERATIONS FOR ENDOSCOPIC
PROCEDURES
For a conscious, cooperative patient, careful orotracheal topical anesthesia and
intravenous sedation may be adequate for the performance of brief, atraumatic
laryngoscopic procedures, such as vocal cord injection. For more complicated
procedures, induction of general anesthesia can proceed after topical anesthesia of the
tongue and oropharynx followed by bilateral superior laryngeal nerve block and
transtracheal instillation of local anesthetic solution. An endotracheal tube may or may
not be inserted. In most procedures a small-diameter, cuffed endotracheal tube does not
obstruct the view of the larynx and allows efficient gas exchange and protection of the
airway from blood. Some surgical techniques necessitate complete absence of an
endotracheal tube. In these situations, intravenous agents and neuromuscular relaxants
meet the requirements of general anesthesia, whereas oxygenation and ventilation occur
through a ventilating laryngoscope or an Albert Sanders injector. High-frequency
positive-pressure ventilation is an alternative approach. Topical anesthesia combined with
general inhalational or intravenous anesthetics also can be used for bronchoscopy. A
ventilating bronchoscope provides an avenue for gas exchange, although apneic
oxygenation with insufflation of oxygenation through a small-bore catheter placed above
carina sometimes is necessary. An anesthesia machine capable of providing high rates of
fresh gas flow is needed to compensate for the leak that occurs around the bronchoscope.
As in laryngoscopy, pulse oximetry is essential for monitoring patient safety. A small
dose of glycopyrrolate facilitates visualization by reducing secretions.
A controversy exists over the best type of endotracheal tube to minimize the risk of
airway fire during carbon dioxide laser laryngoscopy or bronchoscopy. All tubes, except
metal or ceramic, can ignite in the airway under appropriate conditions. Many
anesthesiologists use an ordinary polyvinyl chloride or red rubber endotracheal tube that
has been closely wrapped down its entire length with metallic tape designed to reflect the
energy of the laser off the tube. Because the cuff remains uncovered, an explosion or fire
can occur if the laser beam penetrates it. A less serious problem is misdirection of the
laser if the beam comes into contact with the reflective tape. Even a properly wrapped
laser tube can ignite if the endoscopist directs a high-wattage beam of collimated light at
a single spot on the tube for too long. Management of a laser fire in the airway always
demands removal of the burning tube, extinction of the flame with water, and immediate
bronchoscopy to remove debris and assess residual damage to surrounding tissues (17).
Other measures used to reduce the risk of airway fire include the use of a helium-oxygen
rather than an oxygen-air inspired gas mixture, packing the trachea around the cuff of the
endotracheal tube with wet sponges and filling the endotracheal tube cuff with saline
solution rather than air (18,19). All operating room personnel should wear protective
goggles, and the eyes of the patient should be covered to prevent corneal or retinal
thermal injury.

HIGHLIGHTS
Careful preoperative airway assessment, an understanding of
basic anesthesia monitoring and airway equipment, and
judicious use of anesthetic agents known to produce respiratory
depression aid in the prevention of catastrophic airway loss.
Knowledge of anesthetic techniques and pharmacologic
principles allows safe and effective anesthetic management of
nearly every otolaryngologic patient.
Close cooperation between anesthesiologist and surgeon based
on a mutual understanding of the needs of the other is essential
for a successful patient outcome.
CHAPTER REFERENCES
1. Tetzlaft JE. Clinical pharmacology of local anesthetics. Boston: Butterworth-Heinemann, 2000.
2. O'Keefe NJ, Healy TE. The role of new anesthetic agents. Pharmacol Ther 1999;84:233248.
3. Kasemsuwan L, Griffiths MV. Lignocaine with adrenaline: is it as effective as cocaine in
rhinologic practice? Clin Otolaryngol 1996;21:127129.
4. Zide BN, Swift R. How to block and tackle the face. Plast Reconstr Surg 1998;101:840851.
5. McCollum JSC, Dundee JW. Comparison of induction characteristics of four intravenous
induction agents. Anaesthesia 1986;41:995.
6. Study RE, Barker JL. Cellular mechanisms of benzodiazepine action. JAMA 1982;247:21472151.
7. Geller E, Halpern P, Chernilas J, et al. Cardiorespiratory effects of antagonism of diazepam
sedation with flumazenil in patients with cardiac disease. Anesth Analg 1991;72:207211.
8. Shook JE, Watkins WD, Camporesi EM. Differential roles of opioid receptors in respiration,
respiratory disease and opiate-induced respiratory depression. Am Rev Respir Dis 1990;142:895
909.
9. Derskowitz M, Randel GI, Rosow CE, et al. Initial clinical experience with remifentanil, a new
opioid metabolized by esterases. Anesth Analg 1995;81:619623.
10. Onrust SV, Foster RH. Rapacuronium bromide: a review of its use in anaesthetic practice. Drugs
1999;58:887918.
11. Andrews JJ. Anesthesia systems. In: Barash PG, Cullen BF, Stoelting RK, eds. Clinical
anesthesia. Philadelphia: JB Lippincott, 1989:505541.
12. Kelleher JF. Pulse oximetry: a review. J Clin Monit 1989;5:3762.
13. Cooper JB, Newbower RS, Kitz RJ. An analysis of major errors and equipment failures in
anesthesia management: considerations for prevention and detection. Anesthesiology 1984;60:34
42.
14. American Society of Anesthesiologists Task Force on Management of the Difficult Airway.
Practice guidelines for management of the difficult airway: a report. Anesthesiology 1993;78:597
602.
15. Rosenblatt WH, Wagner PJ, Ovassapian A, et al. Practice patterns in managing the difficult airway
by anesthesiologists in the United States. Anesth Analg 1998;87:153157.
16. Ovassapian A, Krejcie TC, Yelich SJ, et al. Awake fiberoptic intubation in the patient at high risk
of aspiration. Br J Anaesth 1989;62:1316.
17. Hermens JM, Bennett MJ, Hirshman CA. Anesthesia for laser surgery. Anesth Analg
1983;62:218229.
18. Pashayan AG, Gravenstein JS, Cassisi NJ, et al. The helium protocol for laryngotracheal
operations with CO
2
laser: a retrospective review of 523 cases. Anesthesiology 1988;68:801804.
19. Sosis MD, Dillon FX. Saline-filled cuffs help prevent laser-induced polyvinylchloride
endotracheal tube fires. Anesth Analg 1991;72:187189.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

12 ENDOCRINOLOGY
Head & Neck SurgeryOtolaryngology
12




ENDOCRINOLOGY
JEFFREY D. BUNN
AMY R. COFFEY
GEORGE H. PETTI, JR.

J.D. Bunn and G.H. Petti, Jr.: Division of Otololaryngology, Loma Linda University Medical Center,
Loma Linda, California.
A.R. Coffey: Department of Otolaryngology, University of Texas Southwestern Medical Center, Dallas,
Texas.


Pituitary
Embryology and Anatomy
Physiology
Dysfunction
Parathyroid Glands
Calcium Metabolism
Thyroid Gland
Physiology
Adrenal Gland
Anatomy and Physiology
Dysfunction
Pancreas
Physiology
Dysfunction
Metabolically Active Tumors
Multiple Endocrine Neoplasia Syndromes
Endocrine Emergencies
Diabetic Emergencies
Chapter References
The field of endocrinology has continued to expand as our understanding of its scope and
function has advanced. The demarcation between the endocrine system and other organ
systems has become blurred as its extension into these systems is better appreciated,
especially in the nervous system and immune system. Hormones act on local tissues in
either an autocrine or paracrine fashion without entering circulation. Distant effects of
hormones on their target tissues require hormonal transport via the circulatory system.
Hormones are classified according to their receptor types on their target tissues and fall
into two major distinctions: cell-surface receptors (e.g., growth hormone [GH] and
parathyroid hormone [PTH] receptors) and nuclear receptors (e.g., thyroid hormone
receptors and steroid receptors).
PITUITARY
Embryology and Anatomy
The pituitary gland lies within the sella turcica in the sphenoid bone. The sphenoid sinus
wall forms the anterior and inferior aspect of the bony sella, giving direct access to the
gland by this route. Soft-tissue boundaries include the lamina dura, forming the floor of
the sella; the cavernous sinus with its contents laterally; the optic chiasm superiorly; and
the diaphragma sellae, forming the dural roof. The blood supply of the pituitary is from
the internal carotid system through the hypophyseal arteries. The predominant venous
drainage is directly into the cavernous sinus system.
The gland is made of two embryologically and histologically distinct lobes. The posterior
pituitary (i.e., neurohypophysis) is derived as an outpouching of the floor of the third
ventricle and consists of nerve endings of neurons whose cell bodies reside in the
supraoptic and paraventricular nuclei of hypothalamus. The neurohypophysis produces
two octapeptides, oxytocin and vasopressin or antidiuretic hormone (ADH), which are
mediated by neural reflexes. These control functions such as uterine contraction, milk
letdown, and blood osmolality. The anterior pituitary (i.e., adenohypophysis) is derived
from the oropharyngeal ectoderm of Rathke's pouch and has no direct nerve supply. It is
controlled by chemical messages released into the anterior pituitary blood supply from
hypothalamic and posterior pituitary cells (hypophysealportal system) and is regulated
by input from many parts of the brain and by feedback from target organs such as the
thyroid, adrenal cortex, and gonads. It is made of distinct cell types that produce
characteristic hormones. Originally, these were classed in three groups: acidophils,
basophils, and chromophobes. Currently, there are five known cell types, which are listed
in Table 12.1 with the primary secretory products associated with each.

TABLE 12.1. CELL TYPE AND PRIMARY
SECRETORY PRODUCTS OF THE ANTERIOR
PITUITARY GLAND



Physiology
Antidiuretic Hormone
ADH, also called arginine vasopressin, is the major posterior pituitary hormone in
humans. Secretion is triggered by central nervous system osmoreceptors and
baroreceptors supplied by cranial nerves IX and X. They respond to an increase of as
little as 2% in plasma osmolality above 280 mOsm/kg or a decrease in circulating volume
of about 10% precipitated by conditions such as hypotension, hypovolemia, and
vomiting.
The two primary regions of the nephron affected by ADH are the medullary thick
ascending Limb of Henle and the collecting duct (Fig. 12.1). The ascending limb is the
diluting segment, where most of the filtered load of sodium chloride is reabsorbed,
developing medullary hypertonicity. ADH increases the water permeability of the
collecting ducts, allowing osmotic equilibration of tubular fluid with the medullary
interstitium, resulting in decreased urine volume.

FIGURE 12.1. Schematic representation of the renal
tubule illustrating the effects of antidiuretic hormone
(ADH) and aldosterone on the collecting ducts
influencing urinary dilution.



Adrenocorticotropic Hormone
Adrenocorticotropic hormone (ACTH), a corticotropin, is derived from the prohormone
proopiomelanocortin, which also contains melanotropins, lipotropins, and beta endorphin.
Pulsatile secretion from the anterior pituitary follows a circadian rhythm and is
responsive to certain stimuli (e.g., pain, hemorrhage, anxiety, pyrogens, hypoglycemia).
The lowest level of ACTH in the serum occurs between 10 p.m. and 3 a.m. and peaks
between 6 and 8 a.m. ACTH actions include stimulation of steroidogenesis by the
adrenocortical cells, lipolysis in fat cells, amino acid and glucose uptake in muscle, the
secretion of insulin by the pancreatic beta cells, and GH secretion by the somatotropic
cells of the pituitary. Regulation of ACTH secretion is under hypothalamic control by
corticotropin-releasing factor and feedback inhibition by circulating adrenal cortisol (Fig.
12.2) (1).

FIGURE 12.2. Diagrammatic representation of the
hypothalamicpituitaryadrenal axis controlling the
secretion of adrenocorticotropin (ACTH). Secretion is
stimulated by corticotropin-releasing hormone (CRH)
released in response to central stimuli and inhibited by
cortisol from the adrenal glands.



Thyroid-stimulating Hormone
Thyroid-stimulating hormone (TSH), a glycoprotein hormone, is produced by the
thyrotropic cells of the anterior pituitary gland. TSH increases concentrations of cyclic
AMP in the thyroid gland, resulting in the phosphorylation of key proteins and leading to
increased size and vascularity of the gland, increased follicular epithelium height,
reduction of the amount of colloid, increase in iodide transport, stimulation of the
synthesis, and release of thyroxine (T
4
) and triiodothyronine (T
3
).
Regulation is somewhat complex (Fig. 12.3). Secretion is stimulated by hypophyseal
thyrotropin-releasing hormone and inhibited by hypophyseal somatostatin and anterior
pituitary growth hormone. Negative feedback of secretion is by T
3
, the major inhibiting
hormone (2). Intracellular T
3
regulates TSH secretion, but plasma T
4
levels correlate
better with TSH release. When serum T
4
approaches the lower limits of normal, TSH
begins to rise exponentially. Of the intracellular T
3
, 75% is derived from conversion of
plasma T
4
by 58-deiodinase and the remainder comes from plasma T
3
uptake.

FIGURE 12.3. Diagrammatic representation of the
hypothalamicpituitarythyroid axis controlling thyroid
hormone production. Thyrotropin-releasing hormone
(TRH) stimulates release of thyroid-stimulating hormone
(TSH), which then acts on the thyroid to release thyroid
hormone. There is feedback inhibition of thyroid
hormone (primarily T
3
), which also inhibits at the level of
the pituitary and possibly the hypothalamus.



Growth Hormone
Growth hormone (GH) is secreted by somatotropic cells. Secretion is pulsatile and peaks
2 to 3 hours into sleep (i.e., stage III or IV). The major actions involve the stimulation of
bone and cartilage growth, nitrogen and protein metabolism, fat metabolism,
carbohydrate metabolism, and soft-tissue growth (3). Secretion is regulated by
hypothalamic peptides. It is stimulated by GH releasing hormone (GH-RH), or
somatocrinin, and inhibited by somatostatin (1). Somatomedins and GH inhibit release by
promoting somatostatin release. Exercise, stress, some neurogenic stimuli, and central -
adrenergic agonists augment secretion, but emotional deprivation in some children, -
adrenergic blockers, and -adrenergic agonists inhibit secretion.
Prolactin
Prolactin is a single-chain peptide similar to GH. It is secreted in a diurnal pattern by the
lactotropic cells of the anterior pituitary gland. Peak secretion occurs in the later hours of
sleep. Prolactin acts directly on the mammary gland to initiate and maintain lactation but
requires preparation of the breast tissue by estrogens and progesterone. It also acts on
receptors on the granulosa cells of the ovary to inhibit follicular steroidogenesis (4).
Follicle-stimulating and Luteinizing Hormones
The glycoproteins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are
secreted by the gonadotropic cells in the anterior pituitary gland. Secretion levels vary in
premenopausal and postmenopausal women with a 3- to 15-fold increase in women after
menopause. In men, FSH acts on the Sertoli's cells to indirectly stimulate
spermatogenesis, and LH acts on the Leydig's cells to stimulate testosterone synthesis (2).
In women, LH acts on multiple ovarian cells. The preovulatory surge is important in
follicular rupture and luteinization. It alone stimulates progesterone and androgen
production and is necessary for the normal secretion of estrogen. FSH acts on the
granulosa cells to stimulate gametogenesis and also stimulates the production of estradiol.
Ovulation is provoked by a combination of an elevated estradiol level and a midcycle rise
in FSH level.
Regulation of secretion is by pulsatile release of gonadotropin releasing hormone
(GnRH) from the hypothalamus, stimulating release of LH and FSH. Secretion is affected
by gonadal steroids by means of a negative feedback mechanism, probably acting at the
pituitary and the hypothalamus (5).
Dysfunction
Central hypothalamic diabetes insipidus is caused by inadequate synthesis or release of
ADH. In 50% of cases, the cause is idiopathic. Other causes include basilar skull
fractures, tumors of the intrasellar or suprasellar regions, encephalomalacia secondary to
cerebrovascular accidents, and the histiocytoses associated with large temporal or
mastoid lytic lesions. Patients who have undergone hypophysectomy are also at risk, but
this complication is unusual now because of better surgical techniques and less pituitary
stalk damage. Symptoms include polyuria (3 to 15 L/day), thirst, nocturia, hyposthenuria
(specific gravity, 1.005), low urine osmolality (less than 200 mOsm/kg of H
2
O), and
plasma hypertonicity (plasma osmolality more than 287 mOsm/kg H
2
O). Treatment is
with Pitressin or 1-deamino-8-D-arginine vasopressin), which has negligible pressor
effects and can be taken as a nasal spray (2).
The syndrome of inappropriate secretion of ADH (SIADH) is a common problem with
numerous causes, including central nervous system infections, pulmonary diseases,
trauma, many drugs, and bronchogenic or gastrointestinal cancers, especially oat cell
tumors. The increased secretion of ADH causes retention of ingested water and
hyponatremia (2).
Excess secretion of ACTH presents as Cushing's syndrome. ACTH deficiency is
associated with symptoms similar to those of Addison's disease, except for the
hyperpigmentation. Sodium and potassium levels are usually normal because aldosterone
secretion is only partly regulated by ACTH; however, low cortisol levels may cause
water retention with subsequent hyponatremia (6). With age, there may be diminished
sensitivity of ACTH to negative feedback by glucocorticoids, and the ectopic ACTH
syndrome is more common due to the increased incidence of malignancies (7).
The mean level of TSH is normally 1.8 mU/mL. This level may rise above 5 mU/mL
when the plasma T
3
and T
4
are still within normal range in early hypothyroidism.
Hypothalamic or pituitary failure prevents TSH levels from rising. TSH levels may be
normal or slightly elevated in secondary hypothyroidism because TSH is not bioactive
(2).
Excess GH secretion early in life is manifested as gigantism and as acromegaly after
growth centers have closed. Deficiencies may be isolated or occur with other hormone
deficiencies with or without an adenoma. If onset is early, the result is short stature;
however, if it occurs with other deficiencies, the diagnosis may be difficult before
puberty, because ACTH and TSH have large secretory reserves. With age, the plasma
somatomedin C level is decreased, basal GH levels fall in females, the sleep-related
pulsatile secretion declines, and the response to GH-RH or insulin-induced hypoglycemia
may be attenuated (7).
Excess prolactin production is the most common hypothalamicpituitary disorder in
clinical endocrinology. The high levels inhibit the release of GnRH from the
hypothalamus, causing hypogonadism (8). Failure of lactation is associated with
deficiency of prolactin due to postpartum necrosis of the pituitary (Sheehan's syndrome
from ischemia caused by hemorrhage or shock), or it can be an isolated deficiency after
an uncomplicated delivery. Pituitary necrosis also is seen in severe anoxia or long-
standing diabetes mellitus.
Pituitary dysfunction can be related to developmental abnormalities associated with
midline structural defects involving isolated or combined cell types. For example,
Kallmann's syndrome, due to the maldevelopment of the olfactory lobes and related
hypothalamic lesions, is characterized by hyposmia or anosmia and an isolated GnRH
deficiency with the associated gonadal dysfunctions (2). Pituitary necrosis is also seen in
severe anoxia or long-standing diabetes mellitus.
Infectious causes include encephalitis, abscess, tuberculosis, or syphilis involving the
hypothalamus or pituitary. A viral infection of selected neurohypophyseal nuclei may be
a possible mechanism of acquired idiopathic diabetes insipidus. Other causes include
noninfectious granulomas or infiltrations, such as the histiocytoses in children and
sarcoidosis or excessive iron deposition from hemochromatosis in adults. In several
autoimmune disorders, there may be circulating antibodies to lactotropic or somatotropic
cells. Lymphocytic hypophysitis is seen in some postpartum women.
Pituitary damage can occur in children as a result of chemotherapy and radiation therapy.
Accidental and surgical trauma is thought to be due to stalk separation or damage. In
other cases, although the gross appearance is normal, abnormal hormones that are not
biologically active may be produced (1).
Pituitary adenomas are classified by hormonal immunostaining of secretory granules
within the cell or cells of origin and by radiologic appearance. Using computed
tomographic or magnetic resonance studies, the tumor is classified as enclosed if there
is no evidence of invasion of the bony sellar floor. Class I tumors or microadenomas are
smaller than 10 mm in diameter, class II tumors or macroadenomas are larger than 10
mm in diameter, and invasive tumors are considered class III if part of the sellar floor is
involved or class IV if all of the floor is destroyed. This classification does not limit the
superior extension of the tumors. Functioning adenomas secrete the hormone(s) related to
its cell(s) of origin. Some adenomas have no hormonal granules (i.e., null cell adenoma)
or may have increased mitochondria (i.e., oncocytoma) (1). Prolactinomas, the most
common type of functional pituitary adenoma (1), can be found as part of the multiple
endocrine neoplasia type I (MEN I) syndrome. Adenomas are thought also to develop as
a result of untreated Addison's disease, congenital adrenal hyperplasia, previous
hypothyroidism, or hypogonadism (1,9). Pituitary changes associated with aging are seen,
such as a diminished capacity to adapt to salt restriction or salt load with age. Basal levels
of vasopressin are increased, but volumepressure stimulation is decreased and kidney
responsiveness may also be reduced (7).
PARATHYROID GLANDS
Parathyroid anatomy and physiology and its pathologic states are discussed thoroughly in
Chapter 115. The following discussion highlights the role of PTH in the regulation of
calcium metabolism.
Calcium Metabolism
Calcium homeostasis depends on the release of PTH and on small amounts of vitamin D
and calcitonin (Fig. 12.4). The function of the parathyroid glands is to maintain calcium
and phosphorus homeostasis. Calcium is important for the formation of intercellular
ground substance, teeth, and bone. At the membrane level, it affects neuromuscular
irritability, muscular contractility, and cardiac rhythmicity. Lack of extracellular calcium
causes tetany and death if not corrected.

FIGURE 12.4. Calcium homeostasis is influenced by
parathyroid hormone, which acts directly on bone and
kidney and indirectly on the intestines by promoting the
formation of vitamin D
3
.



PTH is a peptide of 84 amino acids with an active amino-terminal end and an inactive
carboxy-terminal end. Its secretion by the parathyroid glands is enhanced by a low
ionized serum calcium and a high phosphate level.
Calcitonin, a peptide of 32 amino acids, is produced by the parafollicular C cells of the
thyroid and contributes to calcium homeostasis by suppressing osteoclastic activity in
bone and decreasing the amount of calcium available to the extracellular space. Calcium
circulates in the extracellular compartment in three forms: 47% is ionized and is the free
and active form that is readily used; 47% is bound to albumin and globulin and fluctuates
with the serum protein level; and 6% is bound to anions such as bicarbonate, phosphate,
and citrate.
Calcium is pumped from the extracellular compartment into the intracellular space. When
serum calcium falls, the parathyroids release PTH, which increases osteoclastic activity,
causing resorption of bone and release of calcium; increases resorption of calcium at the
renal tubular cell; increases absorption of calcium from the gastrointestinal tract;
stimulates renal-1-hydroxylase, which allows 1-hydroxylation of vitamin D in the kidney;
and increases excretion of phosphorus in the urine, decreasing the serum phosphorus
level.
Vitamin D is produced from exposure to sunlight or is obtained from the diet. Dietary
calcium is provided by dairy products, green vegetables, nuts, fish, and calcium
supplements. Approximately 1 g of calcium is ingested each day, and most of this is
absorbed in the duodenum and upper jejunum. 1,25-Dihydroxyvitamin D increases the
uptake of calcium at the brush border of the intestine by increasing cellular ATP and
alkaline phosphatase content. At the other end of the cell, calcium is extruded into the
extracellular fluid in exchange for sodium. The inactive vitamin D is transported by
carrier protein to the liver, where it is 25-hydroxylated. It is then transported to the
kidney, where 1-hydroxylation takes place, and it becomes activated to perform its
function in maintaining calcium homeostasis by increasing calcium absorption and
increasing calcium release from bone by osteoclastic activity (3).
THYROID GLAND
A detailed discussion regarding the thyroid gland and its associated diseases can be found
in Chapter 114. The following discussion focuses on the endocrinology of the thyroid
gland.
Physiology
Thyroid hormone affects the metabolic rate and plays a critical role in thermogenesis
from increased energy release and higher oxygen consumption required by the
stimulation of various processes. These processes include actions involved in fetal and
neonatal growth, especially of the brain; glucose, amino acid, and electrolyte transport
into the cell; oxidative phosphorylation; and protein, carbohydrate, and lipid metabolism.
Thyroid hormone increases production of lipogenic enzymes and induces production and
storage of fat in times of excess carbohydrate ingestion (10,11).
The thyroid gland converts iodine into thyroid hormone by organification. Oxidized
iodine attaches to the 3 and 5 positions of tyrosine in the thyroglobulin molecules, which
then couple by oxidation, forming tetraiodothyronine or T
4
10 times more abundantly
than T
3
. The hormonethyroglobulin complex is stored as the colloid at the center of the
cluster of thyroid follicle cells. To release thyroid hormone, thyroid follicular cells form
pseudopodia, creating vesicles by endocytosis. These contain lysosomes that hydrolyze
the thyroglobulin using hydrogen supplied by reduced glutathione, freeing thyroid
hormone for release into the circulation by exocytosis. Organification is blocked by
propylthiouracil and reducing substances used to treat hyperthyroidism. Release is
inhibited by iodine, which affects production of glutathione reductase (10,11).
TSH from the pituitary stimulates the synthesis and release of thyroid hormone from the
thyroid gland, which then exerts feedback inhibition directly on the pituitary thyrotropic
cell by competing with thyrotropin-releasing hormone from the hypothalamus (Fig. 12.3).
After release into the circulation, thyroid hormone is bound to thyroid-binding proteins,
mostly T
4
-binding globulin (70% to 80%), albumin, and transthyretin, to keep the
hormone soluble in plasma and assist with distribution to the cells. A minute amount
circulates freely in the plasma. It is this part that diffuses into the cell and is carried to the
nucleus by binding proteins. Here it stimulates DNA transcription, resulting in the
formation of messenger RNA and the production of various proteins. T
4
binds with 10
times higher affinity to the thyroid-binding globulin, and T
3
binds preferentially to
intracellular sites. Therefore, most T
4
is found in the circulation, and most T
3
is found
within the cells. The amount of free hormone can be affected by drugs that displace
bound hormone (e.g., aspirin in high doses, phenytoin, carbamazepine) and severe
nonthyroidal illness, which reduces the ability to bind thyroid hormone. Binding proteins
are elevated by acute hepatitis, elevated estrogen (e.g., pregnancy, birth control pills,
postmenopausal estrogen), or methadone and are reduced by anabolic steroids, nephrotic
syndrome, or decreased production due to an inherited disorder (10,11).
Most T
4
is secreted by the thyroid gland. It is functionally a prohormone but may have
some metabolic activity itself. Conversion to T
3
, the more metabolically active form,
occurs by monodeiodination in the liver, kidney, and possibly other organs, which
accounts for 80% of the circulating T
3
. During stress or nonthyroid illness, T
4

preferentially converts to inactive reverse T
3
to conserve the body's metabolism by
removal of an iodide from the inner ring, instead of the outer ring as in T
3
. The
deiodinase system is inhibited by fasting, systemic illness, kidney or liver disease, acute
psychiatric illness, severe vomiting of pregnancy, and drugs (e.g., propylthiouracil,
glucocorticoids, propranolol, iodine-containing agents), leading to the accumulation of
reverse T
3
and a fall in T
3
levels (12). Large amounts of T
4
are stored in the thyroid gland
and bound in the circulation to thyroid-binding globulin, thereby prolonging the time for
hormone deficiencies to manifest themselves clinically. Inflammation may cause injury
to the gland with leakage of thyroglobulin, causing elevated levels of T
4
, T
3
,
thyroglobulin, and other iodinated products in the serum (11).
ADRENAL GLAND
Anatomy and Physiology
The adrenal gland consists of the cortex and the medulla. The adrenal medulla is made of
chromaffin cells that secrete norepinephrine and epinephrine in response to fear, anger, or
stress. These hormones result in increased heart rate, raised blood pressure,
vasoconstriction, and altered carbohydrate metabolism (13). The adrenal cortex is further
divided into three zones that secrete five groups of steroids: corticosteroids, aldosterone,
androgens, estrogens, and progesterone. All are derived from cholesterol. The outer
region, the zona glomerulosa, secretes the main mineralocorticoid, aldosterone. Most of
the glucocorticoids, androgens, and progesterone are secreted by cells in the middle, the
zona fasciculata. The inner zona reticularis is responsible for the remainder of the steroids
secreted by the cortex (2,14). This area atrophies in older males and enlarges with
pregnancy and in the summer in women of childbearing age. Unlike the medulla, removal
of the cortex is incompatible with life (2,13). The glucocorticoids are bound to
transcortin, carrying 70% of the circulating cortisol.
Aldosterone secretion, the serum potassium level, and ACTH are controlled mainly by
angiotensin II (Fig. 12.5). It acts on the collecting duct of the kidney, the salivary glands,
and the gut mucosa, causing the excretion of hydrogen and potassium ions in exchange
for sodium ions.

FIGURE 12.5. Aldosterone secretion is influenced by the
interaction of renin, angiotensin, and catecholamines and
acts to maintain blood volume.



Dysfunction
Hyperadrenocorticism
Hyperadrenocorticism causes Cushing's syndrome, characterized by centripetal obesity
with moon facies and buffalo hump, hirsutism, easy bruisability, amenorrhea, manic
behavior or psychosis, osteopenia, muscle weakness, and violaceous striae of the
abdomen, hips, and breasts. Excess of glucocorticoids leads to increased volume and
blood pressure, hypokalemia, negative nitrogen balance, and glucose intolerance because
they are insulin antagonists. The causes include pharmacologic administration of
glucocorticoids or ACTH and pathologic conditions, such as an ACTH-producing
pituitary adenoma, adrenal hyperplasia, adrenal adenomas or carcinomas, or secondary
ectopic ACTH production in some lung, thymus, or pancreatic tumors (14). Presentation
of ectopic ACTH production may be atypical, including hyperpigmentation due to the
stronger melanocyte-stimulating hormonelike properties (2,15). Cushing's syndrome
usually presents in the third to sixth decade of life and occurs more commonly in women.
At surgical exploration, 75% to 90% of these cases are due to corticotropic cell adenomas
with autonomous secretion and are therefore not under hypothalamic control. In the other
10% to 25%, no pituitary tumor is found.
Adrenocortical Insufficiency
Primary adrenocortical insufficiency (i.e., Addison's disease) may be due to destruction
of the gland from autoimmune disease, tumors, infection, hemorrhage, or metabolic
failure in hormone production. Secondary causes are hypopituitarism or suppression by
exogenous steroids, ACTH (e.g., autonomous tumors), or endogenous steroids. The
disease is characterized by fatigability, weakness, anorexia, nausea and vomiting, weight
loss, hyperpigmentation, hypotension, and occasionally hypoglycemia (2,6,15). In
women, the loss of adrenal androgens causes a loss of axillary and pubic hair. The
absence of glucocorticoid causes volume depletion with decreased cardiac output and
function, leading to shock that is sometimes called addisonian crisis.
Overproduction of Aldosterone
Primary overproduction of aldosterone is due to an adenoma (i.e., Conn's syndrome) or
nodular hyperplasia of the zona glomerulosa and is associated with moderate
hypertension, hypokalemia, alkalosis, and normal or slightly increased sodium levels.
Symptoms include muscle weakness, nocturnal polyuria, and cramping of the hands.
Secondary excess is seen in cirrhosis, ascites, the nephrotic syndrome, and with diuretic
use if the patient is volume depleted. In primary overproduction, tests show elevated
aldosterone levels with severely suppressed plasma renin levels that do not respond to
volume depletion; in secondary overproduction, one finds renin levels that are not
suppressed and that may rise using various methods. Congenital or infantile forms of
hypoaldosteronism are due to an enzyme defect in production. In the elderly, the
condition is thought to be caused by an intrinsic renal problem, causing inadequate renin
production. Many patients are diabetic and present with moderate renal insufficiency and
serum potassium levels that are much higher than expected (3).
PANCREAS
Physiology
Pancreatic islet cells produce insulin, glucagon, human pancreatic polypeptide, and
somatostatin. Insulin, derived from proinsulin, consists of an alpha and beta chain
connected by a C peptide. The basal secretion level is raised in a biphasic response to
stimulation. The rapid phase may release stored preformed insulin in response to glucose,
amino acids, glucagon, and some gastrointestinal hormones. With continuous glucose
administration, both preformed and new insulin is released in the delayed phase. Release
is stimulated by the vagal nerve and -adrenergic receptors and inhibited by -adrenergic
blockers, sympathomimetic amines (e.g., epinephrine, norepinephrine), and somatostatin,
which also inhibits glucagon. Stress triggers the release of glucagon, glucocorticoids,
GH, and catecholamines, which are antagonists to insulin, resulting in glycogenolysis,
gluconeogenesis, ketogenesis, lipolysis, and nitrogen wasting. Stress also affects wound
healing, electrolyte and fluid balance, and susceptibility to infection (3).
Dysfunction
There are two types of diabetes mellitus with seemingly different causes, but they are
both associated with similar complications. Type I (i.e., juvenile onset) usually appears in
patients younger than 25 years who are insulin deficient, ketosis prone, and usually not
obese. The cause is thought to be an autoimmune response to beta cells triggered by
infection. The insulin levels of these patients are generally difficult to control. Type II
(i.e., adult onset) has a more gradual onset. Patients are generally obese, over 40 years
old, ketosis resistant, and more stable and easier to control. It is thought to be the more
inheritable form of diabetes. Obesity reduces the number of insulin receptors on insulin-
responsive cells, altering glucose tolerance. With fasting and weight loss, the number of
receptors increases to normal levels (2,16).
In addition to random fasting blood sugar levels, screening for diabetes is accomplished
with the 2-hour postprandial glucose tolerance test, using a fixed amount of glucose after
a 3-day period of carbohydrate loading. Serum glucose determinations are 10% to 15%
higher than whole blood determinations; therefore, it is important to know which test is
performed (2).
Surgical diabetic patients under stress or anesthesia are thought to undergo hormone
imbalances, causing glucose intolerance. They are also at greater perioperative risk due to
disease-impaired cardiovascular, renal, and neurologic systems. Before surgery, careful
assessment of these systems is important, as is assessing glucose control and modifying
the patient's regimen if necessary.
Symptoms of angina, which must be sought, may be absent. Autonomic dysfunction
presents with orthostatic hypotension, nocturnal diarrhea, early satiety, or difficulties
with erections and ejaculations in the male patient. Nocturia, dry mouth, blurred vision,
weakness, palpitations, hunger, and nightmares are symptoms related to poor glucose
control. The effects associated with hypoglycemia may be masked by neuropathies or -
adrenergic blockers (e.g., propranolol).
A thorough examination of the heart and peripheral pulses is necessary with an
examination for bruits and orthostasis. An electrocardiogram should be obtained
preoperatively and postoperatively to detect a silent myocardial infarction. Laboratory
data should include preoperative fasting glucose, electrolytes, blood urea nitrogen,
creatinine, chest radiograph, and clean-catch urinalysis. Long-term control can be
assessed with the hemoglobin A1C determination, which is elevated with high glucose
levels due to incorporation of glucose into the hemoglobin molecule. Levels remain
elevated for 4 to 6 weeks, the lifespan of an erythrocyte. Before surgery, the patient in
ketoacidosis should be stabilized as much as possible or surgery should be delayed to
establish better glucose control or clear up bacteria in the urine (2). Diabetics are at
increased risks for diseases with a predilection for immunocompromised patients, such as
invasive fungal and bacterial infections. In addition, they suffer from poor wound
healing, as may be evident after surgical procedures. The reader is referred to Chapter 20
on perioperative management for further discussion of the surgical diabetic patient.
METABOLICALLY ACTIVE TUMORS
Tumors that arise from cells within the endocrine glands may secrete normal hormones in
abnormal amounts. These cells derive from neural crest, neural ectoderm, or placodal
ectodermal tissue that secrete monoamine (e.g., serotonin) or polypeptide (e.g., insulin)
substances. These tumors are referred to as APUDomas (i.e., amine precursor uptake and
decarboxylation) or neurocrinopathies. Tumor types include islet cell tumors, medullary
carcinoma from the thyroid C cells, pheochromocytomas from adrenal chromaffin cells,
and carcinoid tumors from Kulschitsky or enterochromaffin cells found in almost every
organ of the body.
Carcinoid tumors are the most common of the APUDomas. They occur most frequently
in the ileum and bronchus and have a high incidence of synchronous and metachronous
neoplasms, whether carcinoid or other types of neoplasms. The active tumors secrete
serotonin, although other substances (e.g., histamine, dopamine, substance P) have been
suggested. The carcinoid syndrome includes flushing, diarrhea, cardiac valve disease, and
occasionally wheezing. The mainstay of diagnosis is the 24-hour urinalysis for 5-HIAA,
the major metabolite of serotonin. Treatment is surgical removal or pharmacotherapy to
control the diarrhea and flushing using serotonin antagonists (e.g., cyproheptadine,
methasergide), parachlorophenylalanine, or natural or synthetic somatostatin (9).
Pheochromocytomas are associated with spells and hypertension, either episodic (50%)
or sustained (50%), which is difficult to differentiate from essential hypertension. The
spells include a variety of symptoms, such as headache and acute anxiety or panic attacks
with sweating. The rule of 10s applies: 10% are malignant, 10% occur bilaterally, and
10% are extraadrenal, occurring anywhere along the sympathetic chain from the skull
base to the gonads. These types of tumors are usually called paragangliomas. Active
tumors secrete norepinephrine alone (i.e., paragangliomas) or norepinephrine combined
with epinephrine (i.e., adrenal tumors).
Tumors are diagnosed using 24-hour urinalysis for vanillylmandelic acid, computed
tomography,
131
I-metaiodobenzylguanadine, or ultrasound (9). All patients must be
prepared for surgical excision with 7 to 14 days of -adrenergic blockers.
Phenoxyabenzamine is used orally beginning at a dose of 10 mg given four times each
day and gradually increased to 300 mg daily until postural hypotension develops. A -
adrenergic blocker may be added 48 hours before surgery if the patient has tachycardia or
arrhythmia or if the catecholamine profile shows excess epinephrine secretion.
Propranolol is given in doses of 10 mg four times a day. Both medications are given the
morning of surgery, and large amounts of intravenous fluid are used intraoperatively after
tumor removal to counteract the marked increase in intravascular capacity, which can
cause an acute fall in blood pressure. This occurs because the adrenergic stimulation is
precipitously removed as the secreting tumor is removed (17).
Multiple Endocrine Neoplasia Syndromes
Several neoplastic syndromes involving multiple endocrine glands have been described.
Currently, the favored nomenclature for the most well-established syndromes and their
most commonly encountered neoplasias are listed (Table 12.2). These syndromes are
typically inherited in an autosomal dominant pattern; however, penetrance is variable.

TABLE 12.2. MULTIPLE ENDOCRINE
NEOPLASIA (MEN) SYNDROMES



MEN I is characterized by parathyroid, pancreatic, and pituitary neoplasias. The most
common parathyroid neoplasia is multiglandular hyperplasia. Gastrin-producing islet cell
tumors account for over half of the pancreatic tumors in MEN I and become the greatest
source of morbidity in affected individuals. The most frequent pituitary neoplasm is a
prolactinoma. Other endocrine tumors are unusual in patients with MEN I but may occur.
The genetic mutation responsible for the syndrome occurs in the tumor suppressor gene,
menin, and has been mapped to chromosome 11 (18,19 and 20).
The distinguishing features of MEN IIa are medullary thyroid carcinoma (MTC),
pheochromocytomas, and parathyroid tumors. MTC develops in hyperplastic C cells of
the thyroid and is nearly universal in MEN IIa. Treatment consists of total thyroidectomy
in all known cases and in unaffected carriers identified through prospective screening.
Pheochromocytomas occur in over half of individuals and are typically bilateral and
multicentric. They typically develop much later than MTC; however, when both are
present, the pheochromocytoma should be removed first. Parathyroid hyperplasia is less
frequent compared with MEN I, occurring in 10% to 35%. The genetic abnormality
responsible for MEN IIa is a mutation of the RET proto-oncogene on chromosome 10.
There is a 100% correlation between the presence of the RET mutation and MEN II and
hereditary MTC. Thus, suspected carriers and family members are now being screened
based on polymerase chain reaction techniques to identify carriers of the mutated RET
proto-oncogene (18,19 and 20).
MEN IIb is characterized by MTC, pheochromocytomas, and mucosal neuromas. The
mucosal neuromas are universal and predominantly involve the oral cavity and can
involve other sites of the gastrointestinal tract and the conjunctiva, cornea, and eyelid.
MTC in these patients is more aggressive than in MEN IIa, with metastatic disease
developing in some children before age 1. The incidence of pheochromocytomas and
their clinical course is similar to that of MEN IIa. Hyperplasia of the parathyroid glands
is rare. The genetic mutation is also found in the RET proto-oncogene on chromosome
10; however, the specific point mutation is distinct from that causing MEN IIa (18,19 and
20).
Endocrine Emergencies
Hypercalcemic Crisis
Severe hypercalcemia, or hypercalcemic crisis, predominantly occurs in patients with
advanced previously diagnosed malignancy. Serum calcium levels are typically elevated
at least to 3.5 mmol/L (14 mg/dL); however, symptom severity also correlates with the
rapidity of the calcium elevation. Ionized calcium levels are preferred for diagnosis and
follow-up, as this is the physiologically active fraction. Clinical findings in emergent
cases include hypovolemia, mental status changes, and gastrointestinal symptoms.
Cardiac arrhythmias and renal dysfunction may also complicate the initial course (21).
Two separate mechanisms for malignancy-associated hypercalcemia are currently
accepted. First, many solid tumors secrete a PTH-related protein (PTHrP) that has similar
activity to PTH, although its production is unregulated. Squamous cell carcinoma of the
lung, head and neck, cervix, esophagus, vulva, and skin, in addition to breast cancer,
renal cell, and bladder cancer, are most commonly found to secrete PTHrP. Second,
metastatic and hematogenous tumors produce local intercellular mediators that stimulate
osteoclast activity. These cytokines (tumor necrosis factor beta, interleukin-6, etc.), once
secreted by the tumor cells, act on the local osteoclast population to mediate bone
resorption and calcium liberation (20,21).
Regardless of the underlying etiology, acute symptomatic hypercalcemia requires
aggressive treatment. Initial efforts focus on rehydration. Volume contraction is universal
and results from the osmotic diuresis and decreased glomerular filtration rate, which
accompany uncontrolled hypercalcemia. Fluid replacement with isotonic saline should be
started at 2 to 4 L/day. The use of loop diuretics to stimulate calciuresis is not performed
routinely. Bisphosphonates (e.g., pamidronate) are osteoclast inhibitors and are
considered first-line therapies for hypercalcemic crisis. Volume expansion and
bisphosphonate therapy can normalize most patients' serum levels. However, the rate of
response with the bisphosphonates is 3 to 6 days for calcium normalization. In the
critically ill patient, a more rapid response is desired. Calcitonin reduces calcium levels
within hours by direct osteoclast inhibition, and its ability enhances renal calcium
excretion. Its main drawback is its short-lived effectiveness. Gallium nitrate and
plicamycin are no longer considered first-line therapy because the bisphosphonates have
significantly better toxicity profiles. Glucocorticoids and dialysis are indicated in specific
circumstances (20,21).
Hypocalcemia
Acute or emergent hypocalcemia is uncommon. The typical presentation centers around
the neuromuscular irritability that predominates the clinical picture. Numbness,
paresthesias, cramps, tetany, and seizures are often seen. Laryngeal tetany and cardiac
arrhythmias can result in mortality if not treated immediately. When complicated or
emergent hypocalcemia is suspected, intravenous elemental calcium should be
administered until clinical improvement is observed. Preferably, 100 to 300 mg of
calcium gluconate is given over 10 minutes. Ionized calcium levels should be obtained
and followed until normalization occurs. Ideally, the underlying etiology will be
identified and treated. The most common etiology in the practice of otolaryngology is
hypocalcemia from sudden PTH deficiency, seen after parathyroid or thyroid surgery.
Intravascular ionized calcium levels typically reach their lowest 24 to 48 hours after
surgery. Additional causes of hypocalcemia include rapid intravascular protein binding,
vitamin D deficiency, and PTH resistance. Several anions may also complex with ionized
calcium to decrease the concentration precipitously, such as citrate, bicarbonate, and
phosphate. One other scenario is the hungry bone syndrome most commonly seen after
removal of larger adenomas in elderly patients.
Once the acute situation has been temporized, long-term calcium supplementation is
instituted and may be enhanced with vitamin D, depending on the underlying etiology
and the initial response to oral calcium therapy. Difficult cases may benefit from
evaluation of serum phosphate and magnesium levels, because abnormal levels will
complicate the diagnosis and treatment of hypocalcemia (20,22).
Thyroid Storm
Thyrotoxic crisis is an uncommon complication of thyrotoxicosis. It has become a rare
complication in the surgical patient, and most commonly occurs in medical patients with
known Grave's disease and a precipitating event that leads to an acceleration or
decompensation of their hyperthyroid state. Clinically, patients present in a severe
hypermetabolic state. Fever, tachycardia, and sweating are nearly universal. Arrhythmias
are common, and heart failure and shock may ensue. Motor restlessness and mental status
changes are common. If unrecognized or untreated, stupor, coma, and hypotension
develop, and the course ends in fatality (20,23).
Common precipitating events include other acute illnesses, infections, trauma, and
emergent surgeries. Others include radioiodine therapy, parturition, toxemia of
pregnancy, and diabetic ketoacidosis. Not all cases have identifiable precipitating events;
however, they must be sought to properly treat the patient and avoid additional morbidity.
Diagnosis is based on the history and clinical presentation. Once the diagnosis is
anticipated, treatment should begin before confirmation with laboratory testing. A scoring
system has been devised for grading patients on the severity of their crisis (24).
There are three goals of therapy. First, treatment must focus on controlling the
hyperthyroid state. Propylthiouracil is used first to prevent further synthesis of thyroid
hormone and to limit the peripheral conversion of T
4
to the more physiologically active
T
3
. Iodide is used to block the release of preformed hormone stores from the thyroid
gland. Lithium may be used in cases where iodide is contraindicated. Glucocorticoids are
used routinely and are associated with improved survival. Definitive treatment of the
hyperthyroidism occurs after reaching an euthyroid state with either radioactive
131
I
ablation or surgical excision. The second object of therapy is reestablishing a normal
homeostatic state. Many of the acute manifestations can be controlled with -adrenergic
blocking agents. Propranolol has been used most extensively, but B
1
-selective agents
have theoretic advantages in certain patients (e.g., heart failure, asthma, etc.). Other
measures include volume reexpansion, electrolyte normalization, glucose monitoring, and
treating the hyperthermia. Salicylates should be avoided because they increase the basic
metabolic rate and displace bound thyroid hormone, thereby increasing serum levels.
Cardiac arrhythmias may require pharmacotherapy and anticoagulation. The final goal of
therapy is identifying and treating the precipitating trigger. Mortality from thyroid storm
is still significant (15% to 20%), despite earlier diagnosis and aggressive treatment
(20,23).
Myxedema Coma
Myxedema coma is the end result of chronic untreated hypothyroidism. It is typically
seen in elderly women during the winter months. Most cases are initiated by a
precipitating event such as an infection (35%), medications (e.g., sedatives), cold
exposure, or an exacerbation of another chronic illness. Patients develop symptoms
insidiously, and diagnosis may be delayed. Major clinical findings include hypothermia,
altered mental status, and respiratory suppression. Typical skin changes include
periorbital edema, peripheral edema, dry skin, and signs of anemia. Bradycardia is
common. Progressive depression of the sensorium may result in coma. Early diagnosis is
essential to limit morbidity and mortality. Once the diagnosis is suspected, treatment
should begin. Confirmation with laboratory testing will reveal depressed T
4
levels and
elevated TSH (20,25).
Initial treatment may require respiratory assistance with mechanical ventilation. In
addition, underlying illnesses need attention (pneumonia, heart failure, urinary tract
infection, etc.). Thyroid replacement begins with an intravenous T
4
bolus, followed by
daily maintenance doses. Glucocorticoids are given routinely to prevent the potential
complication of adrenal crisis. Passive measures are used to rewarm the patient, thereby
avoiding rapid vasodilation and possible vascular collapse, which may accompany
aggressive warming measures. Typically, a hyponatremia similar to SIADH is present
and should be treated with free water restriction. Volume expansion should be
accomplished with isotonic crystalloids or whole blood. Response to therapy occurs
within the initial 24 hours and is evident by improvement of hypothermia, bradycardia,
and mental status. Prolonged respiratory assistance is not uncommon. Mortality rates
have improved to approximately 15% to 20% with aggressive treatment (18,20,25).
Diabetic Emergencies
Many of the complications of diabetes are true medical emergencies, including diabetic
ketoacidosis, nonketotic hyperglycemichyperosmolar coma, and hypoglycemia.
Additional characterization and therapeutic protocols for these conditions is beyond the
scope of this chapter, and the reader is directed to the chapter on perioperative
management issues.
Diagnoses, treatment, and emergencies for the disorders discussed in this chapter are
summarized in Table 12.3, Table 12.4, and Table 12.5.

TABLE 12.3. DIAGNOSIS ENDOCRINE
DISORDERS



TABLE 12.4. TREATMENT ENDOCRINE
DISORDERS



TABLE 12.5. EMERGENCIES ENDOCRINE
DISORDERS




HIGHLIGHTS
Secretion of ADH is triggered by an increase of as little as 2%
in extracellular osmolality or a 10% decrease in the circulating
volume. ADH increases the water permeability of the renal
collecting ducts, resulting in decreased urine volume.
Prolactinomas are the most common type of producing pituitary
adenoma and may occur as part of the MEN I syndrome and
parathyroid dysfunction.
PTH is responsible for raising serum calcium levels by
affecting bone osteoclastic activity, kidney clearance, and,
indirectly, intestinal absorption.
T
4
is formed 10 times more abundantly than T
3
and binds with
10 times higher affinity to the thyroid-binding globulin. T3
binds preferentially to intracellular sites and is the more
metabolically active form. Large amounts of thyroid hormone
are stored in the thyroid gland and bound in the circulation;
therefore, it takes a long time for hormone deficiencies to
manifest themselves clinically.
The most useful thyroid function tests for diagnosing
hyperthyroidism or hypothyroidism are the free T
4
index and
the highly sensitive TSH assay.
Screening for diabetes is best accomplished with the 2-hour
postprandial glucose tolerance test using a fixed amount of
glucose after a 3-day period of carbohydrate loading.
Diabetic patients are at greater risk from surgery due to the
complications that result from their disease-affected
cardiovascular, renal, and neurologic systems. Under the stress
of surgery or anesthesia, a hormone imbalance may cause
glucose intolerance.
Before surgical removal of pheochromocytomas, the patient
must be prepared with 7 to 14 days of alpha-blockers (e.g.,
phenoxybenzamine) and possibly propranolol.
MEN syndromes have identifiable genetic mutations that now
necessitate prospective screening of relatives to
prophylactically treat affected individuals.
Both hypercalcemic and hypocalcemic extremes are medical
emergencies and require immediate attention.
Thyrotoxic crisis and myxedema coma are life-threatening
conditions that usually occur after precipitating events in
patients with previously known thyroid disorders.
CHAPTER REFERENCES
1. Imura H. Adrenocorticotropic hormone. Anatomy and histology of normal and abnormal pituitary
gland. In: DeGroot LJ, Besser M, Burger HG, eds. Endocrinology, 3rd ed. Philadelphia: W.B.
Saunders, 1995:355.
2. Marieb NJ. Physiology of the endocrine system. Otolaryngol Clin North Am 1981;14:265.
3. Bilezidian JP. Hypercalcemia. Dis Mon 1988;34:742.
4. Cooke NE. Prolactin: basic physiology. Anatomy and histology of normal and abnormal pituitary
gland. In: DeGroot LJ, Besser M, Burger HG, eds. Endocrinology, 3rd ed. Philadelphia: W.B.
Saunders, 1995:368.
5. Moyle WR, Campbell RK. Gonadotropins. Anatomy and histology of normal and abnormal
pituitary gland. In: DeGroot LJ, Besser M, Burger HG, eds. Endocrinology, 3rd ed. Philadelphia:
W.B. Saunders, 1995:230.
6. Edwards CRW. Addison's disease. In: Besser GM, Thorner MO, eds. Clinical endocrinology, 2nd
ed. Vol. 9. London: Mosby-Wolfe, 1994:2.
7. Mooradian AD, Morley JE, Korenman SG. Endocrinology in aging. Dis Mon 1988;34:398.
8. Vance ML, Thorner MO. Prolactin: hyperprolactinemic syndromes and management: anatomy and
histology of normal and abnormal pituitary gland. In: DeGroot LJ, Besser M, Burger HG, et al.,
eds. Endocrinology, 3rd ed. Philadelphia: W.B. Saunders, 1995:394.
9. Feldman JM. Carcinoid and other metabolically active tumors in the elderly. Clin Geriatr Med
1987;3:743.
10. Bergman DA. Thyroid physiology and immunology. Otolaryngol Clin North Am 1990;23:231.
11. Bethune J. Interpretation of thyroid function tests. Dis Mon 1989;35:552.
12. Forman BH, Roberts DD. Thyroid and parathyroid diseases. Otolaryngol Clin North Am
1981;14:405.
13. Williams PL, Warwick R. Endocrine glands. In: Williams PL, ed. Gray's anatomy, 36th ed.
Philadelphia: W.B. Saunders, 1980:1458.
14. James VHT. Adrenal cortex physiology. In: Besser GM, Thorner MO, eds. Clinical
endocrinology, 2nd ed. London: Mosby-Wolfe, 1994:7.2.
15. Williams GH, Dluhy RG. Diseases of the adrenal cortex. In: Petersdorf RG, Adams RD, et al.,
eds. Harrison's principles of internal medicine, 10th ed. New York: McGraw-Hill, 1983:650.
16. Hoet JJ, Reusens B, Remacle C. Anatomy, developmental biology, and pathology of the
pancreatic islets. In: DeGroot LJ, Besser M, Burger HG, et al., eds. Endocrinology, 3rd ed.
Philadelphia: W.B. Saunders, 1995:1277.
17. Thompson NW. Pheochromocytoma. In: Cameron JL, ed. Current surgical therapy. Philadelphia:
B.C. Decker, 1989:441.
18. Greenspan FS, Strewler GJ. Basic and clinical endocrinology, 5th ed. Stamford: Appleton &
Lange, 1997:192, 753.
19. Thakker RV. Editorial: Multiple endocrine neoplasia-syndromes of the twentieth century. J Clin
Endocrinol Metabol 1998;83:2617.
20. Wilson JD, Foster DW, Kronenberg HM, et al. Williams textbook of endocrinology, 9th Ed.
Philadelphia: W.B. Saunders, 1998: 1627,1172,389.
21. Edelson GW, Kleerekoper M. Hypercalcemic crisis. Med Clin North Am 1995;79:79.
22. Reber PM, Heath H. Hypocalcemic emergencies. Med Clin North Am 1995;79:93.
23. Tietgens ST, Leinung MC. Thyroid storm. Med Clin North Am 1995;79:169.
24. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis: thyroid storm. Endocrinol Metab Clin
North Am 1993;22:263.
25. Jordan RM. Myxedema coma: pathophysiology, therapy and factors affecting prognosis. Med Clin
North Am 1995;79:185.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

13 DEGENERATIVE AND IDIOPATHIC DISEASES
Head & Neck SurgeryOtolaryngology
13




DEGENERATIVE AND IDIOPATHIC DISEASES
TODD E. SAMUELSON
BYRON J. BAILEY

T.E. Samuelson: Fort Worth, Texas.
B.J. Bailey: Department of Otolaryngology, University of Texas Medical Branch at Galveston, Galveston,
Texas.


Bony Lesions of the Skull
Fibrous Dysplasia
Ossifying Fibroma
Paget Disease
Recurrent Parotid Swelling
Autoimmune Parotid Swelling
Mikulicz Syndrome
Midline Destructive Diseases
Wegener Granulomatosis
Lymphomatoid Granulomatosis (T-Cell Lymphoma)
Malignant Lymphoma
Idiopathic Midline Destructive Disease
Polyarteritis Nodosa
Allergic Granulomatosis and Vasculitis
Foreign-Body Granulomas
Nonneoplastic Nontraumatic Subglottic Stenosis
Amyloidosis
Sarcoidosis
Relapsing Polychondritis
Thyroiditis
Hashimoto Thyroiditis
Subacute Thyroiditis
Acute Suppurative Thyroiditis
Reidel Thyroiditis
Chapter References
Degenerative and idiopathic diseases are characterized by diversity and low incidence. In
this chapter, several of the more common degenerative and idiopathic diseases are
organized into groups with similar presentations, and the differences among the diseases
in each group are highlighted.
BONY LESIONS OF THE SKULL
Some of the more common idiopathic bone lesions of the head and neck are discussed
here. Although their radiographic appearance may be similar (Fig. 13.1A and Fig. 13.2),
they can be differentiated by a thorough history and physical examination and appropriate
laboratory evaluation.

FIGURE 13.1. A: Fibrous dysplasia. B: Fibrous
dysplasia. Note how the fibrous elements are confluent
with the bone trabeculae.



FIGURE 13.2. Paget disease. Note the pattern of
thickened bone surrounding osteolucent bone.



Fibrous Dysplasia
Fibrous dysplasia (Table 13.1), a skeletal disorder wherein medullary bone is replaced by
fibroosseous tissue, manifests itself in three clinical forms: monostotic fibrous dysplasia,
polyostotic fibrous dysplasia, and Albright syndrome. Monostotic fibrous dysplasia, the
term applied when the disease is confined to one bone, accounts for 75% to 80% of all
cases. Polyostotic fibrous dysplasia, which accounts for 20% to 25% of patients, is
applied when two or more bones are involved. If polyostotic fibrous dysplasia is
associated with abnormal skin pigmentation, precocious puberty, and other nonskeletal
diseases, it is called Albright syndrome, which accounts for 20% to 25% of all
polyostotic fibrous dysplasia patients.

TABLE 13.1. FIBROUS DYSPLASIA COMPARED
WITH PAGET'S DISEASE



Fibrous dysplasia occurs almost exclusively before age 30. Polyostotic fibrous dysplasia
and Albright syndrome tend to occur in the first decade, and monostotic fibrous dysplasia
usually manifests in the second or third decade. The disease is usually quiescent after
puberty. Polyostotic fibrous dysplasia has a 3:1 female predominance. Monostotic fibrous
dysplasia occurs with equal frequency in both sexes.
Most (90%) patients with fibrous dysplasia are asymptomatic. When symptomatic,
patients may have local swelling, pain, displaced teeth, or nerve-compression symptoms.
The most commonly affected bones are the ribs and femur for monostotic fibrous
dysplasia and the femur and tibia for polyostotic fibrous dysplasia.
About 25% of patients with fibrous dysplasia have head and neck involvement. The
maxilla is the bone most often affected, followed by the mandible. Painless asymmetric
swelling is common.
The typical radiographic finding is an expanded osseous lesion with a poorly defined
margin covered by an eggshell-thin cortex. Fibrous dysplasia also may present
radiographically as a pagetoid lesion or as a sclerotic lesion. It should be considered
when the paranasal sinuses are involved if radiographic studies show a calcified, thick,
enlarged sinus margin and a ground-glass appearance of the mass inside the sinus (1).
Histologically, the fibrous dysplasia lesion reveals marrow replaced by whorled spindle
cells (Fig. 13.1B). One differentiating feature is the lack of osteoblastic rimming, in
which osteoblasts rim the fibroosseous tissue.
The differential diagnosis for fibrous dysplasia often depends on the location and
radiographic characteristic of the lesion. Although the fibrous dysplasia lesion may
appear pagetoid radiographically, it can easily be differentiated clinically. When located
along the sphenoid ridge, it may look radiographically like a meningioma. Fibrous
dysplasia also may be difficult to differentiate from osteomyelitis, which may coexist
with it. A recent report describes the presentation of fibrous dysplasia of the middle
turbinate that resulted in chronic sinusitis and then progressed to a periorbital abscess (2).
Osteosarcoma must always be considered, because 1 in 200 cases undergoes malignant
degeneration. Biopsy should be performed if the diagnosis is in doubt or if malignant
degeneration is suspected. Excision or curettage is indicated if the lesion interferes with
function, progresses in deformity, or undergoes sarcomatous transformation. The primary
goal is contouring to minimize deformity. Recurrence rates reach 20% to 30% with
curettage.
In recent years, refinement in surgical instrumentation and craniofacial surgical
techniques have made more aggressive nondisabling procedures possible. Complete
excision and bone graft reconstruction is possible in some patients (3).
Ossifying Fibroma
Ossifying fibroma is similar to fibrous dysplasia, but its onset, on average, is 10 years
later. Its radiographic appearance is homogeneously dense in head and neck locations,
similar to the appearance of fibrous dysplasia. The ossifying fibroma is usually more
discrete. Histologically, it resembles fibrous dysplasia, but osteoblastic rimming is
present. Treatment consists of excision, and recurrence is rare.
Paget Disease
The demographics and clinical manifestations of Paget disease differ from those of
fibrous dysplasia (Table 13.1). Paget disease rarely occurs before age 40 and most often
occurs between age 55 and 70. Most (90%) patients have polyostotic disease. The
lumbosacral region is the area most frequently involved. Patients with Paget disease are
often asymptomatic but are more commonly symptomatic than those with fibrous
dysplasia. The classic symptoms are enlarging skull, dorsal kyphosis, and bowing of the
legs. The most common symptom is bone pain. Other symptoms that occur as
complications of the disease include spinal root compression, normal pressure
hydrocephalus, and repeated fractures with nonunion.
The classic radiographic findings of Paget disease follow the underlying histologic
process. Initially, there is a lytic phase associated with increased osteoclastic activity with
replacement with vascular stroma, followed by a mixed phase, with increased
osteoblastic activity in addition to the osteoclastic activity, resulting in a mosaic pattern
of bone. This produces the typical cotton wool appearance on the radiograph. During
the final phase, the osteoblastic activity is preeminent. The radiographic picture becomes
one of sclerosis.
Calcium and parathyroid hormone levels may be elevated secondary to the increased
bone turnover, but they are usually normal. Patients with Paget disease often have
elevated alkaline phosphatase levels secondary to increased osteoblastic activity and
increased urinary hydroxyproline levels secondary to increased osteoclastic activity.
In the head and neck, Paget disease occurs more commonly in the skull than in the face,
as seen in fibrous dysplasia. The skull is the third most often involved bone. Here lesions
are typically lytic (i.e., osteoporosis circumscripta) and only slowly progress to the mixed
phase. Paget disease of the jaw rarely occurs before age 40 and is usually bilateral. In
contrast, fibrous dysplasia is usually unilateral and is rare after age 30.
The differential diagnosis for Paget disease includes fibrous dysplasia, osteomyelitis
(which can coexist with it), osteitis fibrosa from primary hyperparathyroidism, and
osteosarcoma. Like fibrous dysplasia, Paget disease can undergo malignant
transformation. Between 1% and 5% of cases degenerate to an osteosarcoma; the 5-year
survival rate is lower than other osteosarcomas. More rarely, Paget disease degenerates to
giant cell tumor, which typically involves the skull and is less aggressive than other giant
cell tumors, which rarely involve the skull and are seen almost exclusively in the long
bones.
Usually, the clinical picture is classic, but a biopsy may help if the diagnosis is in doubt.
The patient with Paget disease is also at risk of developing serious sequelae, including
hypercalcemia, polycythemia, neurologic compression, malignant transformation, and
congestive heart failure. These patients need close follow-up. Medical treatment becomes
necessary when there is impending hypercalcemia, repeated fractures and nonunion,
compression of nerves, and intractable bone pain.
Calcitonin is the drug of choice. It decreases bone turnover and alkaline phosphatase
levels, urinary hydroxyproline, and the risk for heart failure. Disodium etidronate, which
interferes with bone resorption and formation, is especially useful in treating intractable
bone pain. Mithramycin is reserved for resistant cases because it is associated with severe
side effects.
RECURRENT PAROTID SWELLING
The differential diagnosis for recurrent parotid gland swelling includes autoimmune
pseudosialectasis and Mikulicz syndrome (Table 13.2). If the former is localized to the
parotid gland, it is called Mikulicz disease; there are adult and pediatric forms. If
autoimmune parotitis is associated with xerophthalmia or xerostomia, it is called sicca
syndrome or primary Sjgren disease. If primary Sjgren disease is associated with a
connective tissue disorder, it is called secondary Sjgren disease. Mikulicz syndrome is
essentially a term used for all cases of recurrent parotid swelling that are not autoimmune
conditions. It includes three major categories: chronic recurrent sialadenitis, sialosis, and
multinodular gland (4,5 and 6).

TABLE 13.2. DIFFERENTIAL DIAGNOSES FOR
RECURRENT PAROTID SWELLING



At present, the exact cause of Sjgren syndrome continues to be unknown. The Epstein-
Barr virus, cytomegalovirus, human herpesvirus 6, and retroviruses have been implicated
by different studies (7), but convincing proof has not been provided that one of these
viruses is the etiologic agent.
Autoimmune Parotid Swelling
The autoimmune diseases of the parotid gland have a unifying histologic pattern of an
early lymphocytic infiltrate, followed by thinning and fragmentation of the connective
tissue in the terminal or intercalated duct walls with destruction of the acini. The larger
ducts are usually uninvolved unless there is a superimposed infection. The sialographic
appearance is also similar (Table 13.3). It consists of a diffuse pattern of globular
collections of contrast material, originally called sialectasis. It was thought that there was
dilatation of the acini and collection of the contrast material within them. It is now known
that the weakened acini allow extravasation of contrast material, which form extramural
globular collections (Fig. 13.3). There are four progressive radiographic features of
autoimmune parotid swelling: punctate, with spherical collections of 1 mm or less;
globular, with the collections of 1 to 2 mm: cavitary, with large irregular collections of
uneven distribution; and destructive, with no recognizable branching. The latter two
stages represent superimposed infection.

TABLE 13.3. SIALOGRAPHIC APPEARANCE OF
RECURRENT PAROTID SWELLING



FIGURE 13.3. A: Autoimmune parotitis. Note the
diffuse pattern of globular collections of contrast. The
ducts are normal in caliber. B: The globular collections
remain as the dye is allowed to drain.



Autoimmune parotitis usually presents as unilateral recurrent swelling that is painless, of
unpredictable duration, and rarely associated with edema. Most childhood forms resolve
at puberty and do not progress to the latter two radiographic stages. The adult form is 10
times more common. Sjgren syndrome is the second most common connective tissue
disorder, superseded only by rheumatoid arthritis. It may occur at almost any age,
typically between ages 40 and 60, and is more common in women, with a 9:1 female
predominance.
The symptoms include xerostomia, xerophthalmia, and parotid swelling. Filamentary
keratitis, diagnostic of keratoconjunctivitis sicca, is a common finding. The most
common connective tissue disorder associated with secondary Sjgren syndrome is
rheumatoid arthritis. Other extraglandular symptoms include dry skin, vaginal pruritus,
arthralgia, and myalgia.
Patients suspected of having Sjgren syndrome may require laboratory studies to better
define the disease process. Certain humoral antibodies are characteristic of the disease
(Table 13.4). SS-A and SS-B are autoantibodies found exclusively in primary Sjgren
syndrome. Determination of antibodies to specific human leukocyte antigen (HLA)
antigens also can help differentiate the primary and secondary forms. The primary form
has a high correlation with HLA-B8 and HLA-DW3 antibodies. The secondary form is
associated with HLA-DW4 antibody. Rheumatoid factor and antinuclear antibodies may
be present in both disease forms. The erythrocyte sedimentation rate is often elevated in
both forms. Quantitative analysis of immunoglobulins often shows polyclonal
hypergammaglobulinemia.

TABLE 13.4. AUTOANTIBODIES AND HLA-
ALLOANTIGENS IN SJGREN'S SYNDROME



About 5% of patients with Sjgren syndrome develop a lymphoproliferative neoplasm.
The greatest risk for degeneration is seen in patients with the primary form, constant
parotid swelling, and lymphadenopathy. A decrease in serum IgM levels heralds the
progression to malignancy.
A prominent diagnostic tool is the lip biopsy, with the specimen usually obtained just
lateral to the midline on the mucosal surface of the lower lip. From the biopsy, a focus
score is obtained. A focus is 50 or more lymphocytes, histiocytes, or plasma cells. The
score is determined by counting the number of foci in 4 mm
2
. A score greater than 1 is
characteristic of Sjgren syndrome. Siccalike syndrome is similar to Sjgren syndrome
but has a negative biopsy. Treatment of Sjgren syndrome is usually supportive. Oral
steroids or steroid eye drops are usually reserved for severe disability.
Mikulicz Syndrome
Mikulicz syndrome represents several clinical entities in three major groups: recurrent
sialadenitis, sialosis, and multinodular gland. Recurrent sialadenitis presents as a
unilateral, swollen, red, tender gland with purulent discharge, often with pain on
chewing. Sialography reveals dilation and focal narrowing of Stensen duct (Table 13.3,
Fig. 13.4). The peripheral ducts are usually normal. Sialectasis is usually focal and
nonuniform. Because of the distinct clinical picture, sialography is rarely performed on
these patients. The indications for sialography are to demonstrate a stone or stricture, to
differentiate from autoimmune disease, and to evaluate the extent of irreversible ductal
disease. Treatment of recurrent sialadenitis begins with demonstration and removal of
any stones. The patient is further treated with antibiotics, warm compresses, and
sialogogues. In severe cases, excision may be necessary.

FIGURE 13.4. Sialadenitis. Note the distorted ducts with
dilations and strictures.



Sialosis is a recurrent bilateral nontender parotid swelling that occurs almost exclusively
secondary to underlying pathology, including cirrhosis; diabetes; alcoholism;
malnutrition; or ovarian, thyroid, or pancreatic insufficiency. Sialosis also can result from
using sulfisoxazole, phenylbutazone, catecholamines, or iodide-containing compounds
(Table 13.5). Sialography reveals an enlarged gland with normal peripheral ducts that are
merely more spread apart (Table 13.3). Treatment consists of removing the underlying
cause.

TABLE 13.5. UNDERLYING CAUSES OF
SIALOSIS



Multinodular gland represents a group of diseases with lumpy parotid glands. Although
rare, autoimmune sialadenitis can present in this fashion. The remainder of causes include
granulomatous diseases, lymphoproliferative neoplasms, and other tumors (Table 13.6).
Granulomatous diseases involving the parotid include tuberculosis and sarcoid. About
10% to 30% of patients with sarcoid have involved parotids. In Heerfordt syndrome,
sarcoid involves the facial nerve, producing facial swelling, uveitis, and facial paralysis.
Lymphoma often presents like this in the parotid. A computed tomogram-sialogram is
helpful in differentiating this from other causes of parotid swelling. Warthin tumor is the
most common tumor of parotid origin that presents as a multinodular gland.

TABLE 13.6. DIFFERENTIAL DIAGNOSES FOR
MULTINODULAR GLAND



MIDLINE DESTRUCTIVE DISEASES
The differential diagnosis for midline destructive diseases includes Wegener
granulomatosis, lymphomatoid granulomatosis, lymphoma, idiopathic midline
destructive disease, polyarteritis nodosa, allergic granulomatosis, and foreign-body
granulomas. Midline destructive diseases are difficult to differentiate on a clinical basis,
and as a result of the necrosis that occurs with these diseases, an adequate biopsy is
difficult. Best results are achieved if the superficial scab is removed and a generous
biopsy is performed with some normal-appearing tissue (1,8,9).
Wegener Granulomatosis
The most common midline destructive disease is Wegener granulomatosis. Wegener
granulomatosis occurs in all age groups, with a peak incidence from ages 30 to 40, with a
male to female ratio of 3:2. Classically, Wegener granulomatosis includes the diagnostic
triad of necrotizing granulomas of the upper respiratory tract and lungs, focal
glomerulitis, and disseminating vasculitis. If the disease does not involve the kidneys, it
is called limited Wegener granulomatosis. Because of the diversity of organ involvement,
there is a plethora of symptoms. Nasal symptoms include sinusitis, epistaxis, and nasal
obstruction. Serous otitis media and sensorineural hearing loss have been reported. In the
larynx, the ulcerating lesions can cause subglottic stenosis. Pulmonary symptoms include
chest pain, cough, and hemoptysis. Wegener granulomatosis also can present as skin
petechiae or ulcers. Renal symptoms usually appear late in the disease process.
Proteinuria and hematuria herald the onset of glomerulitis. Wegener granulomatosis is
characterized by coagulation necrosis from the vasculitis, multinucleated giant cells, and
palisading histiocytes. The most important differentiating features compared with other
midline destructive lesions are the presence of granulomas and typical
polymorphonuclear cells (Table 13.7, Fig. 13.5). Appropriate laboratory studies to
determine the extent of the disease include chest radiographs, sinus films, and a
urinalysis.

TABLE 13.7. DIFFERENTIAL DIAGNOSIS OF
MIDLINE DESTRUCTIVE DISEASES



FIGURE 13.5. A: Wegener granulomatosis (low
magnification). Note the presence of multiple granulomas
at this magnification. B: Wegener granulomatosis
(medium magnification). At this magnification note the
multinucleated giant cells (M) and the infiltrate of typical
polymorphs.



Azathioprine (Imuran), cyclophosphamide, and steroids are the drugs of choice for
treatment of classic Wegener granulomatosis. In the precyclophosphamide era, the
average survival time was 5 months. Now long-term remissions and cures can be
achieved. The drug should be continued for 1 year after the disappearance of symptoms.
For limited Wegener granulomatosis, trimethoprim-sulfamethoxazole is often used for
treatment. Avoidance of radiation therapy is advised. Relapse is a common problem.
Lymphomatoid Granulomatosis (T-Cell Lymphoma)
Lymphomatoid granulomatosis, polymorphic reticulosis, and lethal midline granuloma
are terms that have been synonymous in the past. It is now accepted that lymphomatoid
granulomatosis is really a type of T-cell lymphoma, which differs from conventional
lymphoma by being composed of a polymorphic rather than a monomorphic infiltrate.
Lymphomatoid granulomatosis occurs primarily in extranodal tissues (e.g., lungs, skin,
central nervous system, kidneys). In contrast, typical lymphomas involve lymph nodes,
bone marrow, and spleen (Table 13.8).

TABLE 13.8. COMPARISON OF
LYMPHOMATOID GRANULOMATOSIS AND
CONVENTIONAL MALIGNANT LYMPHOMA
PRESENTING INITIALLY IN THE SINONASAL
TRACT



Davison et al. (10) stated that polymorphic reticulosis is an angiocentric lymphoma of T-
cell immunophenotype. These lesions are listed as peripheral T-cell neoplasms
(angiocentric lymphomas) in the revised European-American Classification;
histologically, the lesions are angiocentric and angioinvasive lymphoid infiltrates.
Lymphomatoid granulomatosis occurs in all age groups, with the peak incidence between
40 and 50. The male to female ratio for all patients with lymphomatoid granulomatosis is
1.7:1. If the head and neck are involved, the ratio is 3.5:1.
Patients with lymphomatoid granulomatosis commonly present with pulmonary
symptoms, including cough, shortness of breath, and hemoptysis. Other symptoms
include fever, malaise, weight loss, a skin lesion like systemic lupus erythematosus (40%
of patients), and central nervous system symptoms, including ataxia, mental confusion,
and seizures. Splenomegaly, hepatomegaly, and lymphadenopathy only occur if
lymphomatoid granulomatosis is associated with a conventional lymphoma.
The typical presenting sign for the otolaryngologist is ulcerating lesions of the upper
respiratory tract, usually confined to the nose and sinuses. Without biopsy, these lesions
are impossible to differentiate from Wegener disease.
Histologically, lymphomatoid granulomatosis reveals sheets of atypical
polymorphonuclear cells (Table 13.7). It has no granulomas and no palisading histiocytes
(Fig. 13.6). This is in contrast to Wegener granulomatosis, which has typical polymorphs,
granulomas, and palisading histiocytes.

FIGURE 13.6. A: Lymphomatoid granulomatosis (low
magnification). In this patient note the lack of granulomas
and the areas of ischemic necrosis (I). B: Lymphomatoid
granulomatosis (high magnification). A higher power
view reveals the atypical polymorphic cellular infiltrate.



Management includes a chest radiograph to rule out pulmonary involvement (i.e.,
lymphomatoid granulomatosis tends to involve the lungs more often than Wegener
granulomatosis) and a complete blood count to determine whether the patient is anemic
or there is a superimposing infection.
Treatment of lymphomatoid granulomatosis consists of radiation therapy for localized
disease and cyclophosphamide and prednisone for multiregional disease. The overall
mortality rate is high: 50% to 70%. Pulmonary involvement, leukopenia, fever, and
anergy imply a poor prognosis.
Malignant Lymphoma
Twelve percent of those with lymphomatoid granulomatosis degenerate to lymphoma.
Lymphoma may involve the upper respiratory tract without lymphomatoid
granulomatosis (Table 13.7 and Table 13.8). The demographics are similar for both
diseases. In addition to the differences discussed earlier, lymphomas have a worse
prognosis, and treatment, which consists of radiation therapy, is usually unsuccessful.
Chemotherapy is now being used frequently.
Idiopathic Midline Destructive Disease
Idiopathic midline destructive disease is a rare idiopathic disease that remains localized to
the head and neck. It can be differentiated histologically from Wegener granulomatosis
and lymphomatoid granulomatosis. The lesion is composed of sheets of typical
polymorphs. There are no granulomas and no vasculitis. The treatment of choice is
radiation therapy (Table 13.7).
Polyarteritis Nodosa
Polyarteritis nodosa is another vasculitis that may affect the upper respiratory tract. In
contrast to the other causes of vasculitis, polyarteritis nodosa affects only small to
medium-sized arteries. Polyarteritis nodosa rarely affects the lungs (Table 13.7).
Allergic Granulomatosis and Vasculitis
Allergic granulomatosis and vasculitis of Churg-Strauss syndrome is characterized by the
diagnostic triad of asthma, systemic vasculitis, and tissue and peripheral eosinophilia
(Table 13.7). The vasculitis is indistinguishable from polyarteritis nodosa. About 70% of
patients present with nasal symptoms, including polyps, rhinorrhea, obstruction, crusting,
and septal perforation. Histologically, these lesions are similar to Wegener
granulomatosis, with palisading histiocytes, granulomas, vasculitis, and typical
polymorphs. The major difference is the presence of a tremendous amount of
eosinophilia.
Foreign-Body Granulomas
Foreign-body granulomas also present with intranasal ulcers or granulomas. These
lesions occur in patients who use cocaine or patients who have had intramucosal steroid
injections for allergies. Biopsies reveal multinucleated giant cells. The presence of
foreign material (demonstrable by polarized light) and the absence of vasculitis
differentiate this from Wegener granulomatosis (Table 13.7).
Nonneoplastic Nontraumatic Subglottic Stenosis
The differential for nonneoplastic nontraumatic subglottic stenosis includes Wegener
granulomatosis (discussed earlier), amyloidosis, sarcoidosis, and relapsing polychondritis
(Table 13.9). Clinically, these diseases are usually different, and the diagnosis is often
made by a thorough history and physical examination. Biopsy often only confirms the
diagnosis. Occasionally these diseases present with subglottic stenosis alone, especially
with sarcoidosis and amyloidosis. In these cases, special histologic stains are required.
Suspicion is necessary to alert the pathologist to make the correct diagnosis (1,11,12).

TABLE 13.9. DIFFERENTIAL DIAGNOSES FOR
NONTRAUMATIC NON-NEOPLASTIC
SUBGLOTTIC STENOSIS



Amyloidosis
Amyloidosis is a rare disease characterized by the deposition of extracellular fibrillar
proteins in various tissues. It manifests in several different forms: primary systemic,
secondary systemic, localized, myeloma associated, and hereditary-familial amyloidosis
(Table 13.10). These categories account, respectively, for 56%, 8%, 9%, 26%, and 1% of
the cases. Amyloidosis is extremely rare in the pediatric age group (13).

TABLE 13.10. AMYLOIDOSES AND TISSUES
AFFECTED



The primary systemic form affects primarily mesenchymal tissues (e.g., heart, tongue,
and gastrointestinal tract). Secondary systemic amyloidosis is associated with chronic
destructive diseases such as tuberculosis, rheumatoid arthritis, and osteomyelitis. This
form of amyloid affects primarily the kidneys, adrenals, liver, or spleen. Although only
12% of patients with myeloma develop amyloidosis, myeloma-associated amyloidosis is
the second most common form. This form is deposited primarily in mesenchymal tissues
(Table 13.10). Localized amyloid may be primary or secondary but is limited to one site
in the body.
Using light microscopy, all forms of amyloid are identical. Chemical analysis reveals that
primary amyloid and myeloma-associated amyloid are composed of light-chain
immunoglobulins (AL). Secondary amyloid is composed of amyloid protein A (AA).
Localized amyloid may be composed of several different types of protein.
The diagnosis of amyloid is established by biopsy, which is characterized by extracellular
proteins that are green and birefringent under polarized light after staining with Congo
red (Fig. 13.7). Reversibility of the birefringence with potassium permanganate implies
secondary amyloid. Crystal violet also is used to stain for amyloid.

FIGURE 13.7. A: Amyloidosis (low magnification). B:
Under polarized light there is green birefringence.



Generalized amyloid has a much worse prognosis than localized amyloid. As a result,
these patients must be evaluated for generalized disease by a rectal biopsy or a fine-
needle aspiration of the anterior abdominal wall fat; 80% to 90% of patients with
generalized amyloid show positive results with these tests.
Amyloid may deposit in several sites in the head and neck. The tongue is the most
commonly involved area. Of those with primary amyloid, 50% have lingual involvement
and 12% have macroglossia. The orbit is the most common site of deposition for
localized amyloid in the head and neck. Typically, it presents as a painless mass in the
superior orbit. In the larynx, the typical firm gray, red, or yellow deposits also are usually
localized. The true vocal cord is the most common site of deposition in the larynx. The
nodules tend to be diffuse subglottically. Surgical reduction of amyloid lesions is the
treatment of choice. In the University of California Los Angeles series, surgical
management succeeded in improving deglutition, respiration, appearance, and patient
comfort (14).
Laryngeal amyloidosis tissue is relatively fragile and bleeds readily if traumatized.
Anesthetists should be very cautious when intubating patients with laryngeal amyloid
involvement (15).
Sarcoidosis
Sarcoidosis is an idiopathic disease characterized by noncaseating granulomas. It usually
occurs in the third and fourth decade, rarely before age 15, and is relatively more
common in African Americans and Puerto Ricans. Sarcoid granulomas most often
deposit in the lungs and intrathoracic nodes. Generalized adenopathy occurs in 25% to
50% and splenomegaly in 10%. Constitutional symptoms include fever, weight loss, and
arthralgia. Sarcoid may be associated with impaired T-cell function, delayed
hypersensitivity, and anergy. Neural involvement occurs in 4% to 6% of these cases, and
15% to 25% involve the orbit. Sarcoid may deposit in the subcutaneous Darrier Rousey
nodules (Table 13.11, Fig. 13.8).

TABLE 13.11. MANIFESTATIONS OF SARCOID



FIGURE 13.8. Sarcoidosis (low magnification). Note the
subcutaneous noncaseating granulomas.



Head and neck manifestations occur in 10% to 15% of patients (Table 13.12). Cervical
adenopathy is the most common presentation, but the typical yellow subcutaneous
nodules or polyps may deposit anywhere in the upper respiratory tract. In the larynx, they
usually deposit in the supraglottic larynx (16). Dysphonia, dyspnea, and dysphagia are
the usual symptoms. Pathognomonic of laryngeal sarcoid is a diffusely enlarged, pale
pink, turbanlike epiglottis. Lesions in the orbit include orbital masses, lacrimal swelling,
and uveitis. Parotid swelling may occur, with or without facial nerve involvement. Krespi
et al. (17) reported a series of 28 patients who presented with sinonasal tract symptoms.
Nasal obstruction, edema, epistaxis, crusting, and nasal mass were described. Topical,
intralesional, and systemic steroids are the mainstays of treatment.

TABLE 13.12. HEAD AND NECK
MANIFESTATIONS OF SARCOID



Laboratory evaluation includes a chest film to look for intrathoracic granulomas, a skin
test to rule out anergy, and a purified protein derivative test to rule out tuberculosis.
Although nonspecific, angiotensin-converting enzyme levels may be used to follow the
course of the disease; they are increased in 80% to 90% of patients with active disease.
Treatment of sarcoid is oral steroids (18).
Relapsing Polychondritis
Relapsing polychondritis is a rare disorder characterized by inflammation of cartilage and
other tissues, with a high concentration of glycosaminoglycans. The cause of this disease
is unknown, although an immunologic mechanism is theorized.
The diagnosis of relapsing polychondritis usually is made on a clinical basis. It is an
episodic and progressive disease, which may involve recurrent chondritis of both
auricles, nonerosive inflammatory polyarthritis, chondritis of nasal cartilages,
inflammation of ocular cartilages, chondritis of the respiratory tract, or cochlear and
vestibular damage (Table 13.13). Auricular chondritis and arthritis occur in about 50% of
the patients. Nasal, ocular, and respiratory tract involvement each occur in about 15% of
patients. Cochlear and vestibular involvement constitute the rest of the cases.

TABLE 13.13. MANIFESTATIONS OF RELAPSING
CHONDRITIS



Chondritis usually develops rapidly and resolves in 5 to 10 days. Occasionally, it is
associated with lymphadenopathy or arthritis, which is often migratory, and may mimic
rheumatoid arthritis. After several episodes of chondritis, the involved structures often
become deformed. Saddle-nose deformity and cauliflower ear are frequent complications.
Laryngeal involvement is rare. Presenting symptoms include hoarseness, dyspnea, and
rarely hemoptysis. With progression, the laryngeal structures may be involved in a severe
inflammatory response. Laryngeal collapse may ensue. Tracheostomy is essential with
early laryngeal involvement. Indications are severe edema of the glottis and subglottic
regions of the larynx and laryngeal collapse.
Biopsy often reveals a lack of basophilic staining of the cartilage, perichondrial
inflammation, and eventual cartilage destruction and replacement with fibrous tissue. The
erythrocyte sedimentation rate is often increased with active disease. The blood count
may reveal anemia, especially if the disease is complicated by recurrent epistaxis, or
leukocytosis.
The clinical course ranges from mild disease to severe fulminating attacks. Mortality is
generally related to respiratory involvement (i.e., laryngeal collapse) or cardiovascular
disease (e.g., aneurysms or valvular insufficiency). The cause of relapsing polychondritis
is unknown, and treatment is often symptomatic. Steroids have been used in life-
threatening situations. Because of the relapsing nature of the disease, it is uncertain
whether any therapy changes its course.
THYROIDITIS
The syndromes of thyroiditis include five disorders (Table 13.14). These disorders must
be differentiated from each other and from other diseases such as lymphoma, Graves
disease, and neoplasia.

TABLE 13.14. CLINICAL FEATURES OF
THYROIDITIS



Hashimoto Thyroiditis
Hashimoto thyroiditis, the most common form, is goiterous thyroiditis associated with
elevated levels of antithyroid antibodies. It often presents in middle-aged women. A
family history of thyroiditis is common. The disease also is associated with other
autoimmune diseases, including Graves disease.
The presentation is a slowly progressive painless enlargement that is rarely limited to one
area of the thyroid. Microscopically, lymphocytic infiltration, with fibrosis and Hrthle
cell change of the follicular cells, predominates. As more of the gland is involved in the
disease process, there is glandular enlargement caused by compensation of the
uninvolved gland. Rarely, overcompensation with resultant hyperthyroidism ensues.
Typically, the disease progresses to hypothyroidism.
Antimicrosomal antibody is the most specific test for diagnosing Hashimoto thyroiditis.
About 90% of patients have positive titers for this antibody. Titers are also positive in
low levels in Graves disease and subacute thyroiditis. Thyroid function tests may show
hypothyroidism, compensated hypothyroidism with elevated thyroid-stimulating
hormone, or hyperthyroidism or they may be normal. The erythrocyte sedimentation rate
may be elevated, although not to the levels seen in subacute thyroiditis.
Treatment consists of thyroid hormone replacement to decrease the size of the goiter and
to treat the hypothyroidism. If the goiter fails to regress with suppression, the physician
must consider lymphoma or neoplasm, both of which are associated with Hashimoto
thyroiditis. Fine-needle aspiration is useful if there is a dominant cold nodule on the
radionucleotide scanning or suspicion of malignancy. Surgery is indicated if medical
treatment fails to relieve obstructive symptoms, if the diagnosis is in doubt, or for
cosmetic reasons.
Subacute Thyroiditis
Subacute thyroiditis consists of two separate entities: granulomatous and lymphocytic
thyroiditis. Both are rare compared with Hashimoto thyroiditis.
Subacute granulomatous thyroiditis is now thought to be caused by a viral infection. It is
characterized by infiltration of inflammatory cells, especially the characteristic giant
cells, which leads to fairly rapid thyroid swelling and pain that often is associated with a
transient hyperthyroidism as the glandular stores are released. After depletion, a period of
transient hypothyroidism follows, usually lasting a few weeks. Complete recovery occurs
in most cases, with 10% having a persistent goiter.
Subacute lymphocytic thyroiditis is also called painless thyroiditis because of the
characteristic painless development of thyroiditis. This and the presence of a lymphocytic
rather than a giant cell infiltrate differentiate these two diseases. Otherwise, the two
diseases are clinically similar. The lack of fibrosis, Hrthle cell change, and the different
clinical course differentiate it from Hashimoto thyroiditis. Permanent goiter and
hypothyroidism more commonly are seen in subacute lymphocytic thyroiditis than in
subacute granulomatous thyroiditis. Painless thyroiditis most commonly is seen in
postpartum women (i.e., postpartum thyroiditis). One episode usually implies repeated
episodes with each subsequent pregnancy.
Acute Suppurative Thyroiditis
This exceedingly rare form of thyroiditis is characterized by bacterial or fungal (i.e., in
immunocompromised patients) infections. The typical pathogen is Staphylococcus
aureus. The clinical picture of acute suppurative thyroiditis is rapid development of pain,
redness, and swelling of the gland. Treatment consists of antibiotics and surgical drainage
if there is abscess formation.
Reidel Thyroiditis
Reidel thyroiditis is an extremely rare fibrosing thyroiditis of unknown cause. These
patients typically present with gradual onset of local pressure. On examination, the gland
is hard. Pain and tenderness are unusual. The fibrosis may progress to involve the entire
gland or merely produce hypothyroidism. Treatment is thyroid hormone replacement or
surgical release of obstruction (i.e., isthmusectomy), if required.

HIGHLIGHTS
Although radiographically similar, bony lesions of the skull can
be differentiated by their most common site of involvement and
the patient demographics of those involved.
The differential for recurrent parotid swelling includes the
autoimmune diseases and Mikulicz syndrome, which includes
recurrent sialadenitis, sialosis, and multinodular gland.
The sialographic appearance of all types of autoimmune
parotitis is similar (i.e., diffuse spheric collection of contrast
material with normal ductal architecture), but in recurrent
sialadenitis, the ductal system is distorted with dilations and
strictures. Midline destructive diseases are often differentiated
only by their histologic appearance.
Lymphomatoid granulomatosis, polymorphic reticulosis, and
lethal midline granuloma are now thought to be the same
disease, probably a type of polymorphic lymphoma.
The differential for nontraumatic nonneoplastic subglottic
stenosis includes Wegener granulomatosis, amyloidosis,
sarcoidosis, and relapsing polychondritis.
There are four types of amyloidosis: primary systemic,
secondary systemic, localized, and myeloma associated.
Sarcoidosis, characterized by noncaseating granulomas, most
often involves the lungs and intrathoracic nodes; the cervical
nodes are often involved when sarcoid appears in the head and
neck.
The causes of thyroiditis are often differentiated by their
clinical features of onset, associated pain, and persistence of
goiter. Hashimoto thyroiditis, by far the most common form of
thyroiditis, is associated with elevated levels of antimicrosomal
antibody and is most often treated by thyroid hormone
replacement.
CHAPTER REFERENCES
1. Mladina R, Manojlovic S, Markov-Glavas D, et al. Isolated unilateral fibrous dysplasia of the
sphenoid sinus. Ann Otol Rhinol Laryngol 1999;108:11811184.
2. Stoeckli SJ, Moe KS, Kaufmann T, et al. Fibrous dysplasia as a cause of periorbital abscess.
Otolaryngol Head Neck Surg 1999;120:283285.
3. Posnick JC. Fibrous dysplasia of the craniomaxillofacial region: current clinical perspectives. Br J
Oral Maxillofacial Surg 1998;36:264273.
4. Batsakis JG. The pathology of head and neck tumors: the lymphoepithelial lesion and Sjgren's
syndrome, part 16. Head Neck Surg 1982;5:150163.
5. Bell M, Askari A, Bookman A, et al. Sjogren's syndrome: a critical review of clinical
management. J Rheumatol 1999;26:20512061.
6. Fox RI, Tornwall J, Michelson P. Current issues in the diagnosis and treatment of Sjgren's
syndrome. Curr Opin Rheumatol 1999;11:364371.
7. Merne MET, Syrjanen SM. Detection of Epstein-Barr virus in salivary gland specimens from
Sjgren's syndrome patients. Laryngoscope 1996;106:15341539.
8. Gaulard P, Henni T, Marolleau JP, et al. Lethal midline granuloma (polymorphic reticulosis) and
lymphomatoid granulomatosis. Cancer 1988;62:705710.
9. Pickens JP, Modica L. Current concepts of the lethal midline granuloma syndrome. Otolaryngol
Head Neck Surg 1989;100:623630.
10. Davison SP, Habermann TM, Strickler JG, et al. Nasal and nasopharyngeal angiocentric T-cell
lymphomas. Laryngoscope 1996;106:139143.
11. McCaffrey TV, McDonald TJ. Sarcoidosis of the nose and paranasal sinuses. Laryngoscope
1983;93:12811284.
12. Dash GI, Kimmelman CP. Head and neck manifestations of sarcoidosis. Laryngoscope
1988;98:5053.
13. Clevens RA, Wiatrak BJ, Myers MW. Multifocal amyloidosis of the pediatric airway. Arch
Otolaryngol Head Neck Surg 1995;121:229232.
14. Kerner MM, Wang MB, Angier G, et al. Amyloidosis of the head and neck. Arch Otolaryngol
Head Neck Surg 1995;121:778782.
15. Noguchi T, Minami K, Iwagaki T, et al. Anesthetic management of a patient with laryngeal
amyloidosis. J Clin Anesth 1999;11:339341.
16. Benjamin B, Dalton C, Croxson G. Laryngoscopic diagnosis of laryngeal sarcoid. Ann Otol Rhinol
Laryngol 1995;104:529531.
17. Krespi YP, Kuriloff DB, Aner M. Sarcoidosis of the sinonasal tract: a new staging system.
Otolaryngol Head Neck Surg 1995;112:221227.
18. Johns CJ, Michele TM. The clinical management of sarcoidosis. A 50-year experience at Johns
Hopkins Hospital. Medicine (Baltimore) 1999;78:65111.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

14 CONNECTIVE TISSUE DISEASES
Head & Neck SurgeryOtolaryngology
14




CONNECTIVE TISSUE DISEASES
GARY L. SCHECHTER
JAMES A. SALATA
SHAWN D. NEWLANDS

G.L. Schechter and J.A. Salata: Department of OtolaryngologyHead and Neck Surgery, Eastern
Virginia School of Medicine, Norfolk, Virginia.
S.D. Newlands: Department of OtolaryngologyHead and Neck Surgery, University of Texas Medical
Branch, Galveston, Texas.


Systemic Lupus Erythematosus
Head and Neck Manifestations
Treatment
Rheumatoid Arthritis
Head and Neck Manifestations
Treatment
Sjgren Syndrome
Head and Neck Manifestations
Treatment
Systemic Sclerosis
Head and Neck Manifestations
Treatment
Polymyositis and Dermatomyositis
Head and Neck Manifestations
Treatment
Relapsing Polychondritis
Mixed Connective Tissue Disease
Vasculitides
Polyarteritis Nodosa
Churg-Strauss Syndrome
Hypersensitivity Vasculitides
Wegener Granulomatosis
Giant Cell Arteritis
Behet Disease
Cogan Syndrome
Kawasaki Disease
Chapter References
The otolaryngologist and head and neck surgeon can play two important roles in the care
of patients with connective tissue disorders. The first is diagnosis of these disorders based
on clinical findings in the head and neck and a high index of suspicion for these diseases.
The second is in the management of head and neck manifestations of the diseases.
The connective tissue diseases have a pattern of organ involvement that overlaps and
often makes specific diagnosis difficult. When first recognized as a distinct
histopathologic characteristic, the perivascular collagen deposition prompted the name
collagen vascular disease. Their association with immunologic reactions to body proteins
subsequently caused the name change to autoimmune diseases. These entities are,
however, more correctly called connective tissue diseases. Biochemical and ultrastructure
studies indicate that collagen derangement and evidence of autoimmune processes may
not be the primary disease.
The exact cause of connective tissue diseases remains obscure. Specific autoantibodies
are associated with some of these entities (Table 14.1), supporting the presumption of an
autoimmune mechanism (1). Definite evidence demonstrating loss of self-tolerance or
specific antigens is lacking.

TABLE 14.1. AUTOANTIBODY RELATIONSHIPS
IN CONNECTIVE TISSUE DISEASES



The prevailing histopathologic feature of these diseases is a varying amount of
connective tissue and blood vessel inflammation with abundant fibrinoid deposits (Fig.
14.1). It is the tissue distribution of the inflammatory response and the pattern of organ
involvement that differentiate one connective tissue disease from another. The clinical
patterns resulting from this unique tissue response give the members of this family of
diseases their individual names.

FIGURE 14.1. Necrotizing and fibrinoid necrosis is seen
in many connective tissue diseases. This biopsy from a
patient with periarteritis nodosa shows an infiltration of
eosinophils and polymorphonuclear leukocytes with
medial necrosis and intimal proliferation.



SYSTEMIC LUPUS ERYTHEMATOSUS
Systemic lupus erythematosus (SLE) is a common connective tissue disease. The
incidence is 1 in 1,000, with nine women affected for every man. It has a highly variable
course and affects primarily women of childbearing age. Protean systemic manifestations
include photosensitive skin eruptions, serositis, pneumonitis, myocarditis, nephritis,
hypercoagulability, and central nervous system (CNS) involvement. Criteria for the
diagnosis of SLE are outlined in Table 14.2 (2). Death results most often from active
SLE, infections, and atherosclerotic vascular disease, although the survival rate of this
disease is 80% at 10 years and 65% at 20 years (3).

TABLE 14.2. DIAGNOSIS SYSTEMIC LUPUS
ERYTHEMATOSUS (SLE)



Head and Neck Manifestations
The head and neck manifestations of SLE are dominated by skin and mucosal lesions. A
malar or butterfly rash is the first sign of the disease in 50% of patients (Fig. 14.2).
Oral ulcerations are painful and show a pronounced hyperemia and edema with a
tendency for superficial ulcerations and bleeding. Localized telangiectasis may produce a
red halo effect around affected mucosa. Secondary moniliasis and xerostomia are
common. Histologically, mucosal lesions in SLE demonstrate orthokeratosis and
parakeratosis alternating with areas of epithelial atrophy. Keratotic plugging, acanthosis,
and pseudoepitheliomatous hyperplasia are common findings. Superficial, perivascular,
and deep lymphocytic infiltration can be seen throughout the mucosa.

FIGURE 14.2. Facial rash in the butterfly distribution
typical of systemic lupus erythematosus.



Numerous other head and neck problems may be associated with SLE. In 3% to 5% of
well-established cases, there is ulceration or perforation of the nasal septum (4).
Inflammatory changes of the larynx and trachea have been described, including true
vocal fold thickening or paralysis, cricoarytenoid arthritis, and subglottic stenosis (5). Up
to 25% of SLE patients report dysphagia. Acute enlargement of the parotid gland occurs
in 10% of SLE patients and may be unilateral, tender, and confused with acute parotitis.
Xerostomia may become a chronic problem.
Neuropathy is also a major characteristic of SLE, and the cranial nerves are affected in
15% of patients. This may involve the motor supply to the extraocular muscles, the
sensory divisions of the trigeminal nerve, the motor divisions of the facial nerve, the
vestibular portion of the vestibulocochlear nerve, or the optic nerve. Sudden hearing loss
has been described with SLE, although a definitive link has not been established. Such
hearing loss may be due to thrombosis or vasculitis, although temporal bone studies have
been inconclusive (6,7). A definitive link to SLE has been considered but not established.
There is also a nonspecific lymphadenopathy associated with SLE that in some cases
appears to be related to skin or mucosal lesions.
Discoid lupus erythematosus is a subtype of SLE in which cutaneous lesions result in
significant scarring, but there is no visceral involvement. These lesions are well-
demarcated, erythematous, edematous papules that depigment and scar on resolution. The
face is involved in 85% of cases, the scalp in 60%, and the ear in 44%. There also may be
associated leukoplakia of the tongue and oral mucosa.
Treatment
Management of this severe and complex disease requires a rheumatologist (3). Because
many SLE patients are highly photosensitive, avoidance of sun exposure and liberal use
of sunscreens are recommended. The general treatment of SLE includes nonsteroidal
antiinflammatory drugs, topical and low-dose systemic steroids, and antimalarials. Low-
dose methotrexate may be an alternative to systemic steroids. The use of high-dose
systemic steroids and immunosuppressive agents, such as azathioprine and
cyclophosphamide, is restricted to cases with visceral involvement that might lead to
organ (heart, kidney, CNS) damage.
Symptomatic treatment of the head and neck manifestations of SLE, as with all the
connective tissue diseases, is required when the systemic steroids become ineffective.
Many patients complain about the loss of salivary flow and the development of oral and
pharyngeal lesions. Saliva substitutes are helpful. Steroid-based topical solutions for the
treatment of mouth ulcers are effective if delivered efficiently. Ointments and creams
designed for intraoral use are not effective. Mouthwashes are useful when used
frequently and held in contact with the diseased tissues for a few minutes. One such
preparation is Klack's solution, which consists of tetracycline, cortisone,
diphenhydramine, and nystatin. The oral lesions also may be helped with postprandial
cleansing using mouthwashes with stock hydrogen peroxide solution diluted with equal
parts of warm tap water.
RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is an inflammation of synovial tissue with symmetric
involvement of the peripheral joints as the dominant clinical feature. The course is
variable, usually progressive, and may affect nonarticular tissues. RA occurs in 1% of the
population, affecting women two to three times more often than men. Although it may
occur at any age and there is a distinct juvenile variety, it is more common in the fourth
to fifth decade. Its onset may be acute, but more frequently it is insidious, with
progressive joint involvement. Morning stiffness lasting more than 30 minutes or
stiffness after prolonged inactivity are common symptoms. Tenderness and inflammation
in an inactive joint are physical findings specific to RA. Subcutaneous rheumatoid
nodules aid in the diagnosis. Nonarticular manifestations include visceral nodules,
vasculitis, pleural or pericardial effusions, and Sjgren syndrome. The diagnostic criteria
for RA are found in Table 14.3 (8).

TABLE 14.3. DIAGNOSIS RHEUMATOID
ARTHRITIS
a




Head and Neck Manifestations
Articular involvement predominates in the diverse head and neck manifestations of RA,
affecting the ossicles, temporomandibular joints, cricoarytenoid joints, and the cervical
spine. Temporomandibular joint dysfunction may be prominent. Most patients with RA
have temporomandibular joint complaints. Pain or tenderness at the joint or in the
masseter or temporalis muscles, crepitus, limited mobility, or deviation are commonly
reported. Radiographic evidence of joint erosion is often present. Temporomandibular
joint dysfunction in patients with RA may be severe and cause contractures of the
muscles of mastication, producing an anterior open bite deformity (9).
Cricoarytenoid joint involvement in RA is the most frequent cause of arthritis in these
joints. Histologic abnormalities of the cricoarytenoid joints are present in 86% of patients
with RA. Clinically, however, only 30% of the patients with RA are hoarse.
Cricoarytenoid arthritis may present with dyspnea on exertion, anterior neck or ear pain,
fullness in the throat, dysphagia, and aspiration. Hoarseness in RA is usually the result of
cricoarytenoid joint involvement but may be caused by rheumatoid nodules within the
cords and ischemic recurrent nerve paresis or paralysis. The sudden onset of stridor and
dyspnea in a patient with RA is an emergency requiring systemic steroids and possibly
tracheostomy. The oral cavity usually is not involved with abnormalities related to RA
unless there is associated Sjgren syndrome. In an uncommon variant of rheumatoid
vasculitis, there are oral ulcers similar to those seen in polyarteritis nodosa.
The middle ear may be involved in severe cases of RA if synovitis develops in the
ossicular joints, but this rarely result in a conductive hearing loss except during an acute
RA flair. Stiffness in the incudomalleolar and incudostapedial joints does not impair
sound conduction but results in stiffness abnormalities detected on tympanometric testing
(10). Autoimmune inner ear disease has been related to RA, but no definitive mechanism
has been proven.
Treatment
Salicylates, nonsteroidal antiinflammatory agents, gold salts, penicillamine,
hydroxychloroquine, and immunosuppressive agents have been used to suppress the
inflammation in RA. Additional treatment goals include maintaining joint function and
prevention of joint deformities.
SJGREN SYNDROME
Sjgren syndrome is a chronic disorder characterized by immune-mediated destruction of
exocrine glands predominantly but not exclusively the lacrimal and salivary glands (11).
Sjgren syndrome occurs in primary and secondary forms. The primary form is a
diagnosis of exclusion. The secondary form refers to the sicca complex accompanying
any of the connective tissue diseases. Secondary Sjgren syndrome is primarily seen with
RA but is also commonly associated with SLE, scleroderma, and primary biliary
sclerosis. Sjgren syndrome occurs in 1% of the general population and in 10% to 15% of
patients with RA. There is a 9:1 female preponderance; onset occurs between 40 and 60
years of age. In one third of patients with primary Sjgren syndrome, the disorder is
systemic with involvement of extraglandular sites. Sjgren syndrome is associated with
an increased (33 to 44 times) risk of lymphoma.
The common clinical manifestations of Sjgren syndrome include xerophthalmia with
secondary keratoconjunctivitis and xerostomia, with or without salivary gland
enlargement. These manifestations are called sicca complex or sicca syndrome. Minor
salivary gland biopsy usually demonstrates heavy lymphocyte infiltration, although
parotid biopsy may be more sensitive and specific (12). Rheumatoid factor and
antinuclear antibodies are high in most Sjgren syndrome patients. Antibodies directed
toward Sjgren syndrome A (Ro/SS-A) and Sjgren syndrome B (La/SS-B) antigens are
noted in 60% and 30% of patients, respectively. These antibody tests lack specificity
because they are found commonly in patients with SLE, RA, and polymyositis. Many
anti-Ro-positive Sjgren syndrome patients will go on to develop SLE (13). Salivary
gland biopsy is the best single criterion for Sjgren syndrome (specificity 83%,
sensitivity 81%). The diagnostic criteria for Sjgren syndrome are outlined in Table 14.4
(14).

TABLE 14.4. DIAGNOSIS SJGREN'S
SYNDROME
a,b




There is often confusion between the designations Sjgren syndrome and Mikulicz
disease. The latter is swelling of the salivary glands accompanying nonconnective tissue
diseases, such as hyperlipoproteinemia, malnutrition, diabetes, cirrhosis, tuberculosis, and
sarcoidosis. A nonspecific lymphocytic infiltration is seen on biopsy of the salivary
glands of patients with Mikulicz disease. Sjgren syndrome is not related to the divergent
group of systemic diseases associated with Mikulicz disease.
Head and Neck Manifestations
Exocrine gland pathology dominates the head and neck manifestations of Sjgren
syndrome. About 80% of these patients complain of xerostomia, the most prominent
symptom of this disease. These patients report difficulty chewing, dysphagia, changes in
taste, fissures of the tongue and lips, and an increased number of dental caries. Oral
candidiasis and angular cheilitis are frequent complications of dry mouth. Diminished
secretion of tears leads to keratoconjunctivitis sicca and eye complaints including
dryness, burning, itching, and foreign body sensation. Loss of glandular secretions in the
nasal passages cause crusting and secondary epistaxis in 50% of patients and hyposmia in
40% (15). Chronic sinusitis may result from inspissated secretions, and there may be
occlusion of the nasolacrimal ducts. Other manifestations of primary Sjgren syndrome
include intermittent unilateral parotid swelling in 30% of patients and sensorineural
hearing loss.
Treatment
Symptomatic treatment is the primary approach to patients with Sjgren syndrome
because no treatment alters the course of the disease. Patients and their primary care
physicians must be made aware of the deleterious effects of decongestants,
antihistamines, diuretics, and specific drugs used for treatment of cardiovascular and
psychiatric problems that are known to produce a dry mouth. In addition to increasing
oral fluid intake, the use of saliva and tear substitutes and pilocarpine may be helpful.
Nonsteroidal and steroidal antiinflammatories fail to improve salivary flow. Antifungals
are used to treat oral candidiasis. Close supervision by a dentist and preservative dental
treatments are essential (15).
SYSTEMIC SCLEROSIS
Scleroderma, also called systemic sclerosis, is characterized by sclerotic skin changes
that are often accompanied by multisystem disease. Progressive fibrosis of involved
organs is the pathologic hallmark of the disease. Scleroderma may be limited to relatively
benign cutaneous involvement (extremities distal to the elbows and knees and the face
and neck) or may exist as an aggressive systemic disease. The incidence is 3 to 12 new
cases per million per year. Scleroderma has a 3:1 female to male preponderance, with the
median age at onset between 40 and 50 years. Initial presentation includes Raynaud's
phenomenon, edema of the fingers and hands, and skin thickening. The American
College of Rheumatology criteria for scleroderma include one major criteria
(sclerodermatous skin changes proximal to the metacarpal-phalangeal joints) and two of
three minor criteria: sclerodactyly, digital pitting scars, and bibasilar pulmonary fibrosis
on chest radiograph (16). Visceral and often fatal manifestations are seen in the
gastrointestinal tract, lung, heart, and kidneys. Arthralgias and muscle weakness are
common musculoskeletal complaints, and Raynaud's phenomenon is almost universal.
Head and Neck Manifestations
Eighty percent of patients with systemic sclerosis have signs and symptoms involving the
head and neck, and in 30% of these patients the head and neck symptoms were part of the
presenting complaints (17). The typical facies associated with scleroderma consists of
tight skin, thin lips, and vertical perioral furrows (Fig. 14.3). The skin changes are
secondary to the underlying dermal and subcutaneous inflammatory process. Dysphagia
is the most common initial complaint. Abnormal radiographic findings are observed for
the distal two thirds of the esophagus in 80% of patients with systemic sclerosis, and 50%
of these patients are symptomatic. Decreased or absent peristalsis with mild to moderate
dilation is reported, and hiatal hernia is common.

FIGURE 14.3. A: The typical facies of scleroderma:
tight skin, thin lips, and vertical perioral furrows. These
external facial features are secondary to inflammatory
foci in the dermis and subcutaneous tissues. B:
Infiltrations of lymphocytes, plasma cells, and
histiocytes.



In the skin, edema precedes epidermal atrophy and loss of appendages. Eventually, 35%
of these patients develop facial tightness (17). A decreased ability to open the mouth is
the initial complaint in 19% of patients, a manifestation that is secondary to skin changes
and not to temporomandibular joint dysfunction. Additional skin manifestations include
telangiectasias (19%), calcinosis (3%), and linear scleroderma, which usually affects
scalp and limbs, involving the cheeks and chin.
Gingivitis and periodontal membrane thickening are common. Oral tissues demonstrate
edema followed by atrophy and induration of mucosal and muscular tissues. About 25%
of patients report xerostomia, xerophthalmia, or both. Involvement of the larynx occurs,
and almost half of patients with systemic sclerosis complain of voice change (17).
Raynaud's phenomenon of the tongue, an unusual complication, may present as mucosal
blanching associated with dysarthria. Trigeminal neuralgia and facial nerve palsy are
infrequent manifestations.
Treatment
Randomized controlled trials in scleroderma have failed to reveal effective disease-
modifying therapies. The treatment of systemic sclerosis is symptomatic. Calcium
channel blockers can be useful in Raynaud's phenomenon. Omeprazole is the drug of
choice for reflux esophagitis. Angiotensin-converting enzyme inhibitors are used in the
treatment of renal disease.
POLYMYOSITIS AND DERMATOMYOSITIS
The inflammatory myopathies are a group of disorders characterized by proximal muscle
weakness and nonsuppurative inflammation of skeletal muscle. Polymyositis and
dermatomyositis are subsets of this group. The incidence of these disorders is estimated
to be 5 new cases per million persons annually. There is a 2:1 female preponderance. The
age at onset is between 40 and 60 years, and a pediatric variant affects children between 5
and 15 years of age. The diagnostic criteria for polymyositis and dermatomyositis are
complex and evolving (18).
The inflammatory myopathies may be isolated or associated with other abnormalities.
Polymyositis and dermatomyositis may be associated with other connective tissue
disorders, including systemic sclerosis, SLE, and RA. In about 20% of patients, the
myopathy is associated with a malignancy, particularly ovarian cancer, but cancer of the
lung, prostate, breast, and colon have been implicated. Peng et al. (19) reported an
increased incidence of nasopharyngeal carcinoma in patients with dermatomyositis living
in an endemic area for this neoplasm.
Head and Neck Manifestations
Head and neck manifestations of polymyositis reflect proximal muscle involvement. Half
of patients report weakness of the neck muscles. Difficulty in phonation and deglutition
occurs because of diseased tongue muscles. Nasal regurgitation is common because of
palatal and pharyngeal muscle involvement. Thirty percent of patients with these diseases
have dysphagia secondary to involvement of the upper esophagus, cricopharyngeus,
pharynx, and superior constrictors. Dysfunction of these muscle groups also results in
aspiration and secondary pneumonia. The skin lesions of dermatomyositis vary, but there
is a predilection for sun-exposed areas.
Treatment
Steroids are used to treat symptomatic patients. Methotrexate and other
immunosuppressive agents are used in patients who do not tolerate or respond to steroids.
Upper gastrointestinal symptoms related to esophageal dysfunction may require
omeprazole, cisapride, and referral to a speech therapist.
RELAPSING POLYCHONDRITIS
Relapsing polychondritis is characterized by episodic recurring inflammation of
cartilaginous structures that are eventually replaced by granulation tissue and fibrosis.
Women (3:1) are more commonly affected than men, and the average age at onset is 47.
There appears to be a racial predilection for whites. Defined features of the disease
include recurrent chondritis of the auricles, nonerosive inflammatory polyarthritis,
chondritis of the nasal cartilages, ocular inflammation, chondritis of laryngeal and/or
tracheal cartilages, and cochlear or vestibular damage (20). Diagnosis requires three of
these features without histologic confirmation, two of these features with response to
steroids or dapsone, or any one feature with histologic confirmation.
Auricular chondritis and nonerosive arthritis are the most common presenting symptoms
of relapsing polychondritis. Auricular chondritis is characterized by the sudden onset of
erythema and pain, sparing the lobule, which lacks cartilage. It is the feature presentation
in 33% of patients and will develop in 90% of those with the disease. Resolution occurs
in 5 to 10 days with or without treatment (20). Patients may develop conductive hearing
loss secondary to collapse of the external auditory canal, and 40% suffer cochlear or
vestibular dysfunction, possibly due to vasculitis of the internal auditory artery.
Chondritis of the nasal cartilages develops in 75% of patients and often does not coincide
with the auricular involvement. The nasal cartilage chondritis also has a sudden onset and
a resolution, which resolves in several days with or without treatment. After the
cartilaginous inflammation subsides, deformities result from the loss of cartilage. These
are disfiguring in the ear, and often cause a classic saddle deformity of the nose.
Laryngeal involvement presents early with a nonproductive cough, which progresses to
hoarseness and stridor. Fifty-three percent of patients with relapsing polychondritis will
have respiratory tract involvement during the course of their disease. Diagnostic
endoscopy is dangerous in these patients due to the risk of tracheal collapse (21). With
extensive airway involvement, management is difficult even with tracheotomy. In most
cases, corticosteroids are the main form of treatment. The antileprosy sulfone dapsone
also has helped in some cases, and methotrexate is playing an increased role.
MIXED CONNECTIVE TISSUE DISEASE
The term mixed connective tissue disease was coined in 1972 to describe a distinct entity
with coexisting features of SLE, systemic sclerosis, polymyositis, and dermatomyositis.
This entity is characterized by high titers of anti-U1 RNP, a ribonucleoprotein antibody.
The prevalence is unknown, and no consensus diagnostic criteria have been developed.
However, 80% of patients are women, and onset usually occurs between the ages of 30
and 60. Death results primarily from pulmonary fibrosis and hypertension.
Head and neck manifestations are a combination of the features seen in the other
connective tissue disorders. Mucocutaneous changes include malar rash, discoid lupus,
sclerodermatous skin thickening, oral mucosal ulceration, and nasal septal perforation.
Sicca complex has been described. Esophageal dysfunction is present in most cases,
resulting in abnormal peristalsis, heartburn, and dysphagia in 60%, 48%, and 38% of
patients, respectively. As with most other connective tissue diseases, corticosteroid and
immunosuppressive agents are the mainstays of treatment.
VASCULITIDES
The vasculitides are a group of diseases characterized by a noninfectious necrotizing
vasculitis and resultant ischemia. Considerable overlap in the clinical manifestations of
these diseases makes it difficult to develop categories with strict criteria. A practical
approach has been to classify them into groups by the size of vessels involved, the
specific anatomic sites involved, and the clinical manifestations. Some of the more
important ones are discussed here.
Polyarteritis Nodosa
Polyarteritis nodosa has been considered the prototype of the vasculitides. This rare
disease has an incidence of less than 1 in 100,000 per year. It affects males and females
equally and is seen in all racial groups. Patients are usually in the fifth and sixth decades
of life at presentation. The vasculitis involves small and medium-sized arteries and can be
the result of hepatitis B infection. Tissues involved include the gastrointestinal tract,
hepatobiliary system, kidney, pancreas, skin, testicles, peripheral nerves, and the skeletal
muscles. Symptoms at presentation are primarily constitutional (fever, weight loss, and
malaise) with peripheral neuropathy (mononeuritis multiplex).
Despite widespread arterial involvement, otolaryngologic manifestations are few, but
sudden bilateral sensorineural hearing loss can be seen. Vestibular disturbances also have
been reported. The proposed mechanism of cochleovestibular damage is thromboembolic
occlusion of the end arteries of the inner ear. Other head and neck manifestations include
cranial nerve palsies, in which the seventh nerve is most commonly involved and skin or
mucosal lesions.
Churg-Strauss Syndrome
Churg-Strauss syndrome, also called allergic angiitis granulomatosis, is a disease
consisting of systemic small-vessel vasculitis, extravascular granulomas, and
hyperesosinophilia. It occurs in patients with preexisting asthma and allergic rhinitis. The
vasculitis generally presents with peripheral neuropathy or pulmonary infiltrates. Tissue
eosinophilia is another feature of this disease.
Hypersensitivity Vasculitides
The hypersensitivity vasculitides are a heterogeneous group of small-vessel vasculitides
that universally involve the skin, arteritic involvement of small vessels (particularly
postcapillary venules), and leukocytoclasis. Diseases in this group include
hypersensitivity angiitis, Henoch-Schnlein purpura, and cryoglobulinemia vasculitis.
These syndromes appear immune complex mediated and may be triggered by a foreign
antigen, which is often not identified. Therapy is concentrated on identification and
elimination of inciting antigens. Glucocorticoids, immunosuppressive drugs, and
plasmapheresis are commonly used in treatment.
Wegener Granulomatosis
Wegener granulomatosis is a rare (incidence of less than 1 in 100,000 per year) form of
vasculitis characterized by the triad of respiratory tract granulomas, vasculitis, and
glomerulonephritis (Wegener's triad). There is no sex predilection. Most patients are
white and present in the fifth decade of life. The typical clinical features include bilateral
pneumonitis (95% of patients), chronic sinusitis (90%), mucosal ulceration of
nasopharynx (75%), and evidence of renal disease (80%) (22). The nasal symptoms
usually occur early in the disease and include crusting, epistaxis, and rhinorrhea. Erosion
of the septal cartilage with saddle-nose deformity and nasal stenosis may occur after the
vasculitis and granulomata destroy cartilage.
Recurrent sinusitis is the most common problem in patients with Wegener
granulomatosis. In some cases, the clinical picture of vasculitis first becomes apparent
when the patient has a workup before nasal sinus surgery. In others, it is not until excised
sinus mucosa is evaluated histopathologically that the diagnosis of vasculitis is
established. Repeated nasal mucosal biopsies are often required as acute inflammation
can obscure the subtle changes of vasculitis.
The most common oral cavity findings of Wegener granulomatosis include hyperplasia of
the gingiva and gingivitis. Edema and ulceration of the larynx are seen in 25% of
patients. Significant subglottic stenosis develops in 8.5% of patients and is a poor
prognostic sign (23). Salivary glands may also be involved. Otologic problems develop in
20% to 25% of patients and include conductive hearing loss secondary to serous otitis
media; suppurative otitis media, with or without granulation tissue in the middle ear;
sensorineural hearing loss, often profound and bilateral; and pinna changes similar to
those seen with polychondritis (24). Facial nerve palsies also have been documented.
The diagnosis is based on the clinical, pathologic, and laboratory findings. The hallmark
pathologic lesion in Wegener granulomatosis is necrotizing granulomatous vasculitis
(Fig. 14.4). The discovery of cytoplasmic staining antineutrophil cytoplasmic antibody
(c-ANCA) has revolutionized the diagnosis of Wegener granulomatosis. The sensitivity
of c-ANCA for Wegener granulomatosis ranges from 65% to 90%, and the specificity is
quite high, although this test may be positive in patients with polyarteritis nodosum and
Kawasaki disease. Despite the high specificity, however, tissue diagnosis must be used to
confirm the diagnosis (25).

FIGURE 14.4. A: Wegener granulomatosis involving the
palate. B: This lung biopsy from a patient with Wegener
granulomatosis demonstrates the typical vasculitis and
necrotizing tissue reaction.



Left untreated, Wegener granulomatosis is fatal within 2 years in 93% of cases. However,
good control is achieved with corticosteroids and low-dose daily cyclophosphamide.
Azathioprine or methotrexate may be alternatives to cyclophosphamide. Isolated sinus
disease may be treated with low-dose steroids, topical nasal steroids, saline irrigations,
and antibiotics when bacterial superinfection is suspected. Airway compromise may be
alleviated with systemic steroids, although significant subglottic stenosis may require
tracheostomy.
Giant Cell Arteritis
Giant cell (temporal) arteritis is characterized by focal granulomatous inflammation of
arteries of medium and small size (Fig. 14.5). Giant cell arteritis is the most common of
the vasculitides, and its prevalence increases with age to about 20 per 100,000 persons
aged 50 years and older. It is a general arteritis of which temporal arteritis is only one
local manifestation. Many believe this disease also encompasses polymyalgia rheumatica.
Polymyalgia rheumatica is a clinical syndrome of muscular pain and morning stiffness in
the proximal muscle groups without inflammatory joint or muscle disease. Patients with
polymyalgia rheumatica have histologic changes in the arteries that are like those in
temporal arteritis. In addition, polymyalgia rheumatica is seen in 50% of patients with
classic giant cell arteritis. Systemic symptoms, such as low-grade fever, weight loss, and
malaise, may precede localized symptoms in all manifestations of the disease.
Polymyalgia rheumatica alone is usually self-limiting and responds well to low-dose
prednisone therapy. The symptoms of classic giant cell arteritis reflect involvement of the
cranial blood supply by the vasculitis. Headache is the initial symptom in 47% of
patients. It is the most common symptom, of variable character, and occurs in as many as
90% of patients.

FIGURE 14.5. Giant cell arteritis typically affects
arteries with an elastic lamina. This temporal artery
biopsy demonstrates the characteristic
polymorphonuclear and mononuclear infiltration, medial
necrosis, disruption of the elastic lamina, and giant cell
formation.



Despite the name, the temporal artery is erythematous and tender in only 50% of patients
with giant cell arteritis. The scalp, however, is often very tender. Jaw claudication occurs
in as many as 50% of these patients, and 25% have lingual claudication. Vertigo and
hearing loss also have been reported. Involvement of the ascending pharyngeal artery can
lead to dysphagia. Cranial nerve deficits, vertebrobasilar insufficiency, and psychosis
reflect intracranial disease. Blindness occurs in a third of untreated patients and may be
heralded by field defects or amaurosis fugax.
In giant cell arteritis, as with several of the vasculitides, the erythrocyte sedimentation
rate (ESR) is usually more than 50 mm/h. Although cases with normal or slightly
elevated ESRs have been reported, those results usually lead the clinician away from the
diagnosis. Confirmation of diagnosis of giant cell arteritis is accomplished with a biopsy
of the temporal artery on the most symptomatic side. If the initial biopsy is negative, the
contralateral side should be biopsied. False-negative results range from 5% to 40% (26).
The treatment is with corticosteroids. Normalization of the ESR or C-reactive protein and
loss of symptoms are the therapeutic guidelines. The purpose of treatment is both the
elimination of pain and prevention of blindness and other vascular complications.
Therapy may be required for 5 years or longer.
Behet Disease
Behet disease is a vasculitis affecting Japanese and Mediterranean populations that
usually presents in the third decade with oral and genital ulcers and uveitis or iritis. These
aphthous-like ulcers are characteristically punched out, with or without surrounding
erythema, and are covered with a pale pseudomembrane. They are frequently the first
symptom of the disease. They are painful lesions that occur singly or in clusters on the
lips, gingiva, buccal mucosa, and tongue and are seen less often on the palate and in the
oropharynx. The genital ulcers are similar but are deeper and larger. Healing occurs in a
few days or weeks, and some scarring results. Symptoms may occur simultaneously or
months apart. Morbidity is secondary to CNS involvement, arthritis, and large-vessel
arteritis. Eye involvement is seen in 43% to 72% of patients and loss of sight occurs in
25%. Local treatment for oral and genital ulcers is primarily through the use of
corticosteroid creams. Local treatment for eye involvement includes topical mydriatics
and corticosteroid injections. Fever is treated with antipyretics or nonsteroidal
antiinflammatories. Colchicine, azathioprine, methotrexate, corticosteroids, and dapsone
are used systemically.
Cogan Syndrome
Cogan syndrome is a rare disease of young adults (median age 22) characterized by
Mnire-like audiovestibular dysfunction, interstitial keratitis, and nonreactive tests for
syphilis. The symptoms frequently begin after an upper respiratory infection.
Audiovestibular manifestations are usually bilateral and can include fluctuating hearing
loss, vertigo, tinnitus, and aural pressure (27). These symptoms may resolve
spontaneously and reappear months later. The hearing loss is progressive and severe and
usually associated with decreased or absent vestibular responses on caloric testing.
Bilateral deafness results in 65% of cases. The ear symptoms may precede or follow the
ocular disease by several years. Often, Cogan syndrome is accompanied by a large- or
medium-vessel systemic vasculitis. Pathologic features suggest end-organ specific
autoimmune mechanisms rather than vasculitis damage to the inner ear. Hearing
outcomes are improved with early initiation of systemic corticosteroid treatment so early
diagnosis is critical. Permanent visual loss is rarely seen.
Kawasaki Disease
Kawasaki disease, also known as mucocutaneous lymph node syndrome, is a disease of
the pediatric age group and the most common cause of acquired heart disease in children
in the developing world. The cause is unknown, but epidemiologic data suggest an
infectious cause. Clinical characteristics include fever, conjunctivitis, red and dry lips,
erythema of the oral mucosa, polymorphous truncal rash, desquamation of the fingers and
toes, and cervical lymphadenopathy. Although cervical adenopathy is the least common
feature, seen in 50% to 75% of patients, this disease must be considered in febrile
children with cervical lymphadenopathy unresponsive to antibiotics without an
alternative diagnosis. Twenty percent to 25% of untreated children develop coronary
artery dilation or aneurysms, and a small percentage die from myocardial infarction due
to thrombosis or rupture of coronary aneurisms, usually from 2 to 12 weeks after onset of
disease. Treatment with intravenous -globulin and aspirin in the first 10 days of illness
reduce the incidence of coronary abnormalities 10-fold.

HIGHLIGHTS
Connective tissue diseases result from immunologic or
autoimmune reactions.
The prevailing histopathologic feature of these diseases is
inflammation of blood vessels and connective tissues with
associated fibrinoid deposits.
The tissue distribution of the inflammatory response, the pattern
of organ involvement, and the presence of specific
autoantibodies are the factors that differentiate one connective
tissue disease from another.
The common head and neck manifestations of connective tissue
diseases are skin rash, oral mucosal lesions, cranial neuropathy,
hearing loss, and xerostomia.
RA often is associated with temporomandibular and
cricoarytenoid joint disease.
Salivary gland biopsy and laboratory tests, such as SS-A and
SS-B antibodies, aid in confirming the diagnosis of Sjgren
syndrome.
Systemic sclerosis and polymyositis-dermatomyositis often
involve the esophagus and must be considered in the
differential diagnosis of dysphagia and esophageal dysmotility.
Sudden unexplained onset of erythema and pain over the
cartilages of the nose or ear suggest a diagnosis of
polychondritis.
There may be significant overlap in the clinical presentation of
the connective tissue diseases, and if there are distinct clinical
characteristics of several of these diseases in any one patient,
the diagnosis of mixed connective tissue disease should be
considered.
Chronic sinusitis that fails to respond to usual medical and
surgical therapy or is associated with pulmonary or glomerular
diseases should be considered Wegener granulomatosis until
proven otherwise.
CHAPTER REFERENCES
1. Nakamura RM, Tan EM. Update on autoantibodies to intracellular antigens in systemic rheumatic
diseases. Clin Lab Med 1992;12:123.
2. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic
lupus erythematosus. Arthritis Rheum 1982;25:12711277.
3. (No authors listed). Guidelines for referal and management of systemic lupus erythematosus in
adults. Arthritis Rheum 1999;42:17851796.
4. Alcala H, Alarcon-Segovia D. Ulceration and perforation of the nasal septum in systemic lupus
erythematosus. N Engl J Med 1969;281:722723.
5. Martin L, Edworthy SM, Ryan JP, et al. Upper airway disease in systemic lupus erythematosus: a
report of four cases and review of the literature. J Rheumatol 1992;19:11861190.
6. Naarendorp M, Spiera H. Sudden sensorineural hearing loss in patients with systemic lupus
erythematosus or lupus-like symptoms and antiphospholipid antibodies. J Rheumatol
1998;25:589592.
7. Sone M, Schachern PA, Paparella MM, et al. Study of systemic lupus erythematosus in temporal
bones. Ann Otol Rhinol Laryngol 1999;108:338344.
8. Arnett FC, Edworthy SM, Block DA, et al. The American Rheumatism Association 1987 revised
criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315324.
9. Koh ET, Yap AU, Koh CKH, et al. Temporomandibular joint disorders in rheumatoid arthritis. J
Rheumatol 1999;26:19181922.
10. Giannini P, Marciano E, Saulino C, et al. Middle ear function in rheumatoid arthritis: a multiple
frequency tempanometric study. Clin Exp Rheumatol 1996;14:243247.
11. Van der Reijden WA, Vissink A, Veerman ECI, et al. Treatment of oral dryness related
complaints (xerostomia) in Sjgren's syndrome. Ann Rheum Dis 1997;58:465473.
12. Marx RE, Hartman KS, Rethman K. A prospective study comparing incisional labial to incisional
parotid biopsies in the detection and confirmation of sarcoidosis, Sjgren's disease, sialosis and
lymphoma. J Rheumatol 1988;15:621629.
13. Provost TT, Watson R, Simmons-O'Brien E. Anti-Ro(SS-A) antibody positive Sjgren's/lupus
erythematosis overlap syndrome. Lupus 1997;6:105111.
14. Vitali C, Bombardieri S, Moutsopoulos HM, et al. Preliminary criteria for the classification of
Sjgren's syndrome. Arthritis Rheum 1993;36:340347.
15. Manoussakis MN, Moutsopoulos H. Sjgren's syndrome. Otolaryngol Clin North Am
1999;32:843860.
16. Subcommitte for Scleroderma Criteria of the American Rheumatism Association Diagnostic and
Therapeutic Criteria Committee. Preliminary criteria for the classification of systemic sclerosis
(scleroderma). Arthritis Rheum 1980;23:581590.
17. Weisman RA, Calcaterra TC. Head and neck manifestations of scleroderma. Ann Otol Rhinol
Laryngol 1978;87:332339.
18. Medsgar TA, Oddis CV. Classification and diagnostic criteria for polymyositis and
dermatomyositis. J Rheumatol 1995;22:581585.
19. Peng JC, Shen TS, Hsu MM. Nasopharyngeal carcinoma with dermatomyositis. Arch Otolaryngol
Head Neck Surg 1995;121:12981301.
20. McAdam LD, O'Hanlan MD, Bluestone R, et al. Relapsing polychondritis. Medicine (Baltimore)
1976;55:193215.
21. Spraggs PD, Tostevin PM, Howard DJ. Management of laryngotracheobronchial sequelae and
complications of relapsing polychondritis. Laryngoscope 1997;107:936941.
22. Fauci AS, Haynes BF, Katz P, et al. Wegener's granulomatosis: prospective clinical and
therapeutic experience with 85 patients for 21 years. Ann Intern Med 1983;98:7685.
23. Waxman J, Bose WJ. Laryngeal manifestations of Wegener's granulomatosis: case reports and
review of the literature. J Rheumatol 1986;13:408411.
24. McCaffrey RV, McDonald TJ, Facer GW, et al. Otologic manifestations of Wegener's
granulomatosis. Otolaryngol Head Neck Surg 1980;88:586593.
25. Sneller MC. Wegener's granulomatosis. JAMA 1995;273:12881291.
26. Ferguson BJ, Allen NB, Farmer JC. Giant cell arteritis and polymyalgia rheumatica. Ann Otol
Rhinol Laryngol 1987;96:373379.
27. St. Clair EW, McCallum RM. Cogan's syndrome. Curr Opin Rheum 1999;11:4752.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

15 GRANULOMATOUS DISEASES OF THE HEAD AND NECK
Head & Neck SurgeryOtolaryngology
15




GRANULOMATOUS DISEASES OF THE HEAD
AND NECK
MARK C. LITTLEJOHN
BYRON J. BAILEY
JOHN K. YOO

M.C. Littlejohn: Longview, Texas.
B.J. Bailey and J.K. Yoo: Department of Otolaryngology, University of Texas Medical Branch at
Galveston, Galveston, Texas.


Neoplastic Disorders
Histiocytosis X
Eosinophilic Granuloma
Hand-Schller-Christian Disease
Letterer-Siwe Disease
Fibrous Histiocytoma
Lobular Capillary Hemangioma
Necrotizing Sialometaplasia
Inflammatory Diseases of Unknown Etiology
Sarcoidosis
Idiopathic Midline Destructive Disease
Autoimmune or Vasculitic Disease
Wegener Granulomatosis
Goodpasture Syndrome
Relapsing Polychondritis
Systemic Lupus Erythematosus
Sjgren Syndrome
Periarteritis Nodosa
Churg-Strauss Syndrome
Behet Disease
Foreign-Body Reactions
Cocaine-induced Midline Granuloma
Cholesterol Granuloma
Gout
Infectious Diseases
Bacterial Infections
Fungal Infections
Parasitic Infections
Trauma-Induced Disorders
Intubation Granuloma
Teflon Granuloma
Reparative Granuloma
Pyogenic Granuloma
Acknowledgments
Chapter References
A granuloma is a lesion produced by a defensive immunopathologic process. Initially, a
circulating monocyte acquires additional cytoplasm and organelles in the process of
removing inflammatory debris. If the phagocytic mechanism fails, the cell becomes inert
and immobile (i.e., epithelioid) and becomes a relatively functionless multinucleated
Langerhans' giant cell with lymphocytes and eosinophils surrounding it. Fibroblastic
proliferation occurs around the involved cells, forming a granuloma.
If a patient presents with a nonhealing ulcerative lesion, a mucosal tumor, or a mass in
the head and neck, a biopsy is frequently performed to rule out neoplastic disease. The
pathologist often reports only the presence of granulation tissue consistent with acute and
chronic inflammation. The differential diagnosis may be lengthy, and the physician's first
task is to determine whether the lesion is a localized disease process or a regional
presentation of a systemic disease.
The investigation begins with a thorough history, with special reference to fever, night
sweats, weight loss, loss of appetite, malaise, arthralgias, and other factors suggesting
systemic disease. A history of recent travel to developing countries and the possibility of
immunocompromise are important factors.
Physical examination includes a search for cervical, axillary, or inguinal
lymphadenopathy or hepatosplenomegaly. If the first biopsy is inadequate, a subsequent
specimen should be obtained from the superficial margins or the depth of the lesion.
Tissue also is sent for special stains and culture. Preoperative consultation with the
pathologist or microbiologist ensures proper collection and transportation of specimens.
Laboratory evaluation should include a complete blood count, erythrocyte sedimentation
rate, rapid plasmin reagin, serum protein electrophoresis, urinalysis, serum electrolytes,
liver function studies, lupus erythematosus preparation, antinuclear antibody, circulating
immune complexes, purified protein derivative, and antigen skin tests. A chest radiograph
and computed tomography (CT) of the head and neck should be considered. An accurate
diagnosis is necessary because surgery, irradiation, chemotherapy, antimicrobials, or
immunosuppressants are considerations in the treatment of granulomatous disorders of
the head and neck.
NEOPLASTIC DISORDERS
Histiocytosis X
The unifying feature of the disorders classified under histiocytosis X is their
histopathology, which consists of sheets of polygonal histiocytes with a variable number
of eosinophils, plasma cells, and lymphocytes. These unique histiocytes contain
cytoplasmic inclusions known as X bodies and are called Langerhans' cells. As a result,
several authors have recommended changing the nomenclature from histiocytosis X and
its various subtype eponyms to being collectively called Langerhans' cell histiocytosis.
Otitis media is the most frequent otologic finding in patients with histiocytosis X. Other
possible presentations are listed in Table 15.1 (1).

TABLE 15.1. PRESENTATIONS OF
HISTIOCYTOSIS X



Eosinophilic Granuloma
Eosinophilic granuloma, the localized form of histiocytosis X, occurs in children and
young adults. This disorder is characterized by osteolytic lesions in one bone (i.e.,
monostotic) or in several bones (i.e., polyostotic), with a predilection for the frontal and
temporal bones. Treatment is surgical excision. Radiation therapy is reserved for
recurrences or inaccessible lesions. This disease carries an excellent prognosis (1).
Hand-Schller-Christian Disease
Hand-Schller-Christian disease is the chronic disseminated form of histiocytosis X:
Some investigators describe this process as the polyostotic form of eosinophilic
granuloma. This entity occurs in children past infancy and in young adults, but it is also
reported in the elderly. A classic triad, occurring in 10% of cases, consists of skull
lesions, exophthalmos, and diabetes insipidus. Patients with this condition can be treated
with radiation therapy, surgery, chemotherapy, or a combination, but despite treatment
the mortality is about 30% (1).
Letterer-Siwe Disease
Letterer-Siwe disease is the acute disseminated form of histiocytosis X. Infants and
children aged younger than 3 years old are affected. Extraskeletal involvement
predominates. This disorder is uniformly fatal (1).
Fibrous Histiocytoma
Benign fibrous histiocytoma (BFH) most often develops as a painless mass lesion and
most commonly occurs in sun-exposed skin and orbital tissues, but it has been found in
the upper aerodigestive tract, salivary glands, and deep layers of the scalp and face. Age
range is 1 to 70 years with a male-to-female ratio of 2.5:1. The most common symptoms
include nasal obstruction, epistaxis, dysphagia, and dyspnea (2).
The histopathology of BFH consists of a biphasic cell population of fibroblasts and
histiocytes with spindle-shaped cells with elongated nuclei arranged in a storiform
(cartwheel) pattern. The malignant variant can be differentiated by its histopathology,
which consists of malignant pleomorphic sarcomatous cells, bizarre giant cells, and more
abundant mitotic figures and by its greater tendency for perineural, vascular, mucosal,
and bony invasion. Treatment of BFH is local excision with clear margins (2).
Lobular Capillary Hemangioma
Lobular capillary hemangioma is sometimes called pyogenic granuloma, although this
term is also used to describe granulation tissue not caused by hemangioma.
Histologically, lobular capillary hemangioma consists of circumscribed aggregates of
capillaries arranged in lobules (Fig. 15.1). These are seen on the lip (38% of patients),
nasal cavity (29%), tongue (18%), and oral mucosa (15%). Sixty percent of nasal lesions
arise on the septum. These lesions characteristically bleed intermittently, but they are
painless. In patients younger than 18 years, lobular capillary hemangioma occurs
predominantly in males (82%), but there is a female predominance (86%) among patients
18 to 39 years old. Sex distribution probably is based on hormonal factors because
lobular capillary hemangioma in pregnant women shows marked regression with delivery
and progesterone increases the size of the vessels in the oral cavity lesions in animals.
Surgical excision is the treatment of choice.

FIGURE 15.1. Lobular capillary hemangioma. The
tongue biopsy revealed ulcerated squamous mucosa with
lobular proliferation of capillaries and inflammation
(hematoxylin & eosin stain; original magnification, 10).



Necrotizing Sialometaplasia
Necrotizing sialometaplasia is a lesion characterized by metaplastic epithelial cells lining
small salivary gland ducts with preservation of lobular architecture, unlike squamous cell
or mucoepidermoid carcinoma. This process may be found wherever salivary tissue is
present, but it occurs most often in the oral cavity, and the junction of the hard and soft
palate is the most frequently involved site. This lesion presents as a deep-seated and
sharply demarcated ulcer, but a nonulcerated swelling may be the only manifestation.
This entity is more common in persons who smoke. Spontaneous resolution over the
course of weeks to months is the rule.
INFLAMMATORY DISEASES OF UNKNOWN ETIOLOGY
Sarcoidosis
Sarcoidosis is a multisystem granulomatosis. The cause is unknown, and the clinical
course varies from spontaneous resolution to relentless progression and death.
Sarcoidosis becomes evident most often in the third to fifth decades, and there is a
predilection for blacks and females. Forty percent of patients with sarcoidosis are
asymptomatic, and incidental discovery by chest radiograph is the most common
presentation. The lesions exhibit discrete noncaseating epithelioid granulomas (Fig.
15.2). When laryngeal involvement is present, the supraglottic region is the most
commonly affected area. Organ system involvement outside the head and neck is shown
in Table 15.2 (7) (see Chapter 13).

FIGURE 15.2. Sarcoidosis. Lung biopsy shows
noncaseating granulomas with giant cells (hematoxylin &
eosin stain; original magnification, 10).



TABLE 15.2. SYSTEMIC INVOLVEMENT OF
SARCOIDOSIS



Idiopathic Midline Destructive Disease
The cause of idiopathic midline destructive disease is unknown, but if it is not treated, it
is uniformly fatal. Patients may present with pansinusitis and ulceration of the nasal floor,
septum, paranasal sinuses, hard palate, and facial soft tissues. Disease may extend to the
nasopharynx, orbit, larynx, and trachea (see Chapter 13).
AUTOIMMUNE OR VASCULITIC DISEASE
Wegener Granulomatosis
Wegener granulomatosis is a systemic disorder characterized by necrotizing granulomas
with vasculitis in one or more major organ systems and, in most cases, focal necrotizing
glomerulonephritis.
The cause is unknown, but it is thought to be an autoimmune process. Granulomas,
necrotizing vasculitis, and arteritis involving small arteries must be demonstrated for the
diagnosis. Diagnosis is based on the combination of the clinical picture, biopsies, and
exclusion of infectious and other granulomatous diseases. Cytoplasmic staining
antineutrophil cytoplasmic antibodies (c-ANCA) can be used for diagnosing patients with
Wegener granulomatosis due to its high specificity in excess of 90% and for monitoring
clinical status because the titers of c-ANCA closely parallel disease activity (5).
Involvement of any combination of organ systems may occur, except for isolated renal
involvement. This disease is most common in the fourth to fifth decades of life and
exhibits a 2:1 male predominance. The upper tract, lungs, and kidneys are the areas
mainly involved, and radiation therapy is considered the treatment of choice. Head and
neck manifestations are listed in Table 15.3 (see Chapter 13).

TABLE 15.3. HEAD AND NECK
MANIFESTATIONS OF WEGENER'S
GRANULOMATOSIS



Goodpasture Syndrome
Goodpasture syndrome, a form of antiglomerular basement membrane nephritis, is
characterized by hemoptysis, anemia, diffuse pulmonary infiltrates, and
glomerulonephritis. Unlike Wegener granulomatosis, Goodpasture syndrome lacks sinus
involvement.
Relapsing Polychondritis
Relapsing polychondritis is an autoimmune connective tissue disorder characterized by
intermittent inflammation of cartilage. The pinna, nose, trachea, and larynx are most
commonly involved in the head and neck. The lesions are typically red, painful, and
swollen. Destruction of the nasal cartilages can lead to saddle deformity. Treatment
includes nonsteroidal antiinflammatory drugs (NSAIDs), steroids, or dapsone (6).
Systemic Lupus Erythematosus
Systemic lupus erythematosus is a multisystem inflammatory disorder with autoantibody
production, occurring most frequently in young black women. Diagnosis requires
evidence of disease in more than one organ system in association with a disturbance in
the immune system (Table 15.4) (7).

TABLE 15.4. ORGAN SYSTEM INVOLVEMENT
IN SYSTEMIC LUPUS ERYTHEMATOSUS



Laryngeal involvement includes thickening of the true vocal cords, limited excursion of
the arytenoids, perichondritis and chondritis of the laryngeal and tracheal cartilages, and
cricoarytenoid and cricothyroid arthritis. Hoarseness, pain, and obstruction may result.
Nasal cavity dryness with frequent septal ulcers and eventual anterior perforation produce
nasal crusting and intermittent epistaxis. Superficial ulceration with surrounding
erythema of the buccal mucosa or palate may be seen. Autoimmune inner ear disease can
also occur.
NSAIDs, antimalarials, and glucocorticoids are used in therapy. Azathioprine and
cyclophosphamide are reserved for resistant cases (7).
Sjgren Syndrome
Sjgren syndrome is a systemic autoimmune disorder of the exocrine glands that may
occur alone or in conjunction with a connective tissue disease. Diagnosis requires two of
the three hallmarks of the disease: xerostomia, keratoconjunctivitis sicca, and connective
tissue disease. This disorder most frequently occurs in patients between 40 and 60 years
of age and is nine times more common among women than men (see Chapter 13).
Periarteritis Nodosa
Periarteritis nodosa consists of fibrinoid necrosis of medium-sized arteries with frequent
involvement of the kidneys. This disease produces nonspecific nasal mucosal lesions.
Churg-Strauss Syndrome
Churg-Strauss syndrome is characterized by the triad of hypereosinophilia, allergic
rhinitis, and asthma plus a systemic vasculitis of medium and small muscular arteries.
Three phases of this disorder exist. The prodromal phase consists of atopy and allergic
rhinitis. The second phase is marked by hypereosinophilia and eosinophilic tissue
infiltration. Systemic necrotizing vasculitis constitutes the final phase. Seventy percent of
patients have nasal involvement with polyps, resultant obstruction, rhinorrhea, and
crusting. High-dose corticosteroids are the treatment of choice.
Behet Disease
Recurrent aphthous ulceration of the upper aerodigestive tract and genitalia, ocular
inflammation, and cutaneous vasculitis are the hallmarks of Behet disease. The cause is
not understood, and no treatment is known.
FOREIGN-BODY REACTIONS
Cocaine-induced Midline Granuloma
Topical nasal usage of cocaine produces ulceration of midline strictures of the upper
respiratory tract (e.g., septum, nasopharynx, soft palate). This ulcer is usually infected
with Staphylococcus aureus. Treatment of the condition includes cessation of cocaine
usage and administration of appropriate intravenous antibiotics.
Cholesterol Granuloma
Cholesterol granuloma is thought to arise as a consequence of inadequate ventilation,
with impaired drainage and hemorrhage of the middle ear or paranasal sinuses.
Erythrocyte, middle ear mucosa, transudate, or a combination of cell breakdown occurs,
and cholesterol precipitates. The precipitate elicits a foreign-body reaction with
neovascularization and formation of granulation tissue (8).
Although pressure erosion of the sinus wall with orbital or intracranial extension may
occur from the paranasal sinuses, most do not expand or cause bone destruction.
Treatment consists of radical removal and establishment of effective sinus drainage (8).
The symptoms of cholesterol granuloma of the temporal bone are controversial. Some
researchers believe this lesion is asymptomatic and attribute any symptoms to an
accompanying cholesteatoma. Others believe this is an expansile lesion, with resultant
cerebellopontine (i.e., cranial nerves V through VIII) involvement differentiates
cholesterol granuloma from cholesteatoma Table 15.5 (8).

TABLE 15.5. COMPARISON OF CHOLESTEROL
GRANULOMA WITH CHOLESTEATOMA



Gout
The arthritis of gout is usually episodic, self-limited, and monoarticular. Microscopic
examination reveals urate needles that are negatively birefringent. Head and neck
involvement, although rare, consists of two main processes: gouty arthritis and
tophaceous deposits. The most common site of gouty arthritis in the head and neck is the
cricoarytenoid joint, producing pain, dysphagia, hoarseness, aspiration, stridor, and
possible airway compromise, depending on the position of fixation. Tophi in the head and
neck classically involve the helical rim of the pinna. This lesion is usually painless. Gout
is treated with colchicine or indomethacin for acute attacks and with allopurinol for
prophylaxis.
INFECTIOUS DISEASES
Bacterial Infections
Cat-Scratch Disease and Bacillary Angiomatosis
Both cat-scratch disease and bacillary angiomatosis are believed to be caused by the
bacteria Rochalimaea henselae, although the two entities carry different histopathologic
lesions and clinical pictures (9).
Cat-scratch disease is caused by an intracellular, pleomorphic, gram-negative, nonacid-
fast bacillus, R. henselae, and less so by Afipia felis, which may be seen with Warthin-
Starry silver stain. Fifty percent of these patients present with head and neck masses,
usually in children. Tender regional adenopathy and mild fever are common, with 55% to
94% of patients exhibiting a cutaneous lesion at the site of inoculation. Diagnosis is
based on a history of cat exposure, the presence of a primary inoculation site, regional
adenopathy, histologic features of cat scratch in excisional biopsy (suppurative and
necrotizing granulomatous lymphadenitis with stellate abscesses), pleomorphic, Warthin-
Starry silver staining, intracellular bacilli, and failure to demonstrate other causative
agents. Treatment is supportive, with incision and drainage reserved for abscess
formation. Disappearance of lymphadenopathy in 1 to 2 months, regardless of therapy, is
the rule.
Bacillary angiomatosis occurs predominantly in young adults as cutaneous papules and
subcutaneous nodules or masses, but the lesions could potentially affect any organ
system. The causative agent is believed to be R. henselae and, to a lesser degree,
Rochalimaea quintana. Risk factors include cat exposure, human immunodeficiency
virus (HIV), and other immunocompromised states. Histopathology is somewhat
different from that of cat-scratch disease and consists of vascular (lobular capillary)
proliferation with pleomorphic gram-negative bacilli visible on Warthin-Starry stain. The
lesions respond well to rifampin, erythromycin, or doxycycline, but untreated this disease
is progressive and can be fatal (9).
Brucellosis
Brucellosis is caused by an aerobic gram-negative bacilli. Cattle, pigs, goats, elk, and
bison may harbor the pathogen, and humans may acquire the infection from the butter
from one of these animals. Weakness, sweating, chills, malaise, headache, backache, and
arthralgia are common. Fever peaks in the afternoon. Granuloma formation in the head
and neck also may occur. Diagnosis is based on a history suggesting exposure and serum
titers. Tetracycline is the treatment of choice (23).
Rhinoscleroma
Rhinoscleroma is caused by Klebsiella rhinoscleromatis. The natural course of the
disease is outlined in Table 15.6. The sinuses, lacrimal gland, and cervical nodes also
may be involved. Diagnosis is based on finding the characteristic honeycomb-color
crusting in the nose in patients with prolonged rhinorrhea and a history of travel to
Central America or Eastern Europe. A culture demonstrating vacuolated histiocytes (i.e.,
Mikulicz cells) corroborates the diagnosis. Streptomycin or tetracycline are the standard
forms of treatment, and dilatation is used if necessary (10).

TABLE 15.6. PROGRESSION OF
RHINOSCLEROMA



Leprosy
Leprosy (Hansen disease) is contracted by exposure to Mycobacterium leprae through
open ulcers of lepromatous skin, nasal discharge, or breast milk. Table 15.7 lists the
common manifestations of leprosy (11). Patients must be treated with dapsone for the rest
of their lives.

TABLE 15.7. COMMON MANIFESTATIONS OF
LEPROSY



Nontuberculous Mycobacteria
Nontuberculous mycobacteria are usually less virulent than Mycobacterium tuberculosis;
however, they are also less responsive to standard antituberculous drugs. Because of a
predilection for colonizing the upper respiratory tract, repeated positive cultures are more
significant than a single culture. Children aged 1 to 6 years are most frequently affected,
and nontuberculous mycobacteria more commonly causes cervical lymphadenopathy than
tuberculosis (12). The route of transmission is from soil to mouth or eye. Altered
immunologic status frequently exists (12). In fact, the prevalence and virulence of
nontuberculous mycobacterial disease have increased in the age of the HIV epidemic,
especially the Mycobacterium avium-intracellulare complex, which is recognized as a
common opportunistic infection in the acquired immunodeficiency syndrome.
The most common head and neck manifestation is corneal ulceration. Next in prevalence
is cervical lymphadenopathy, which is usually unilateral, with the anterior cervical,
preauricular, and submandibular nodes most commonly affected. Discrete nodes arise
quickly, adhere to overlying skin, and rapidly progress to abscess (12). Nontuberculous
mycobacteria (Mycobacterium fortuitum and M. avium) can be rare causes of mastoiditis
with a presentation similar to that of tuberculous mastoiditis, including chronic painless
otorrhea and exuberant middle ear granulation tissue.
Diagnosis is by culture and sensitivity testing of a biopsy specimen; cultures take 2 to 4
weeks for most species, but techniques including the polymerase chain reaction are being
developed for more rapid identification of mycobacterial species and drug-resistant
strains. Acid-fast staining may provide a presumptive diagnosis before positive culture
results are available. A recent study found that 58% of lymph nodes in children in whom
granulomatous inflammation was diagnosed grew mycobacteria on culture, and a high
index of suspicion is necessary for diagnosing a child with a pathologic diagnosis of
granulomatous inflammation. Purified protein derivative is negative or weakly positive
(e.g., 10-mm wheal) (12).
Patients are treated by excisional biopsy, with the subsequent antibiotic regimen based on
susceptibility, although curettage may be considered for fluctuant lesions, lesions with
severe skin necrosis, and lesions close to the facial nerve. Incision and drainage are
contraindicated (12). Nontuberculous mastoiditis should be treated with mastoidectomy
because nontuberculous mycobacterial infections are less sensitive to antituberculous
medications.
Tuberculosis
Scrofula is a nonspecific term, referring to tuberculous or nontuberculous cervical
adenopathy. Tuberculosis is relatively rare in the head and neck. After the microorganism
gains entry, 90% of patients who have a positive purified protein derivative are
asymptomatic, although they may develop disease at any time during their lives if left
untreated (12).
M. tuberculosis is generally transmitted by inhalation of airborne droplets. Less
commonly, direct contact with an open wound may cause infection (12).
There are many manifestations of tuberculosis, and some patients have constitutional
symptoms. Cervical lymphadenopathy is the most common form of head and neck
involvement (Table 15.8). Nodes are multiple, matted, bilateral, firm, and nontender
(10% tender), and frequently they involve the posterior triangles. Laryngeal symptoms
include cough, hoarseness, and weakened voice. A high index of suspicion must be
maintained for laryngeal tuberculosis in patients infected with HIV because of
confounding factors, including multiple causes of systemic symptoms, a carcinoma-like
appearance of the laryngeal tuberculosis lesions, and a tendency toward more posterior
laryngeal involvement (31). Otologic involvement begins with granulomas appearing as
thickened hyperemic spots on the tympanic membrane, which coalesce to form multiple
perforations. These perforations painlessly drain a thin watery discharge. Granulation
tissue then increases, with the discharge becoming thick and cheesy. Mastoiditis may
ensue, with intracranial extension. Mastoid films typically show an absence of bony
destruction and sclerosis, because the process is relatively acute (12).

TABLE 15.8. HEAD AND NECK
MANIFESTATIONS OF TUBERCULOSIS



Diagnosis begins with a positive purified protein derivative, with a 10-mm or larger
wheal deemed positive. If a patient with cervical lymphadenitis has a negative purified
protein derivative test with a positive control, tuberculosis is unlikely, because 98% of
patients with cervical lymphadenitis secondary to tuberculosis have a positive skin test. A
chest radiograph should always be obtained, and CT and ultrasound should be
considered. CT findings include multiloculated low-density nodal mass with enhancing
rims and normal fascial planes. The walls of the nodal mass are also thicker than those
found in malignant disease. With ultrasound, as necrotic caseation and suppuration
continue, the image changes to a low echogenic mass with nonhomogeneity. With further
progression, there is abscess formation with spread into adjacent subcutaneous tissues.
Excisional biopsy also should be considered (Fig. 15.3). A biopsy is obligatory if the
patient recently received antituberculous therapy. As with nontuberculous mycobacteria,
incision and drainage should be avoided (13).

FIGURE 15.3. Tuberculosis. Lymph node reveals
necrosis surrounded by Langerhans' giant cells,
epithelioid histiocytes, and lymphocytes (hematoxylin &
eosin stain; original magnification, 10).



Fine-needle aspiration cytology is useful in evaluating tuberculous lymphadenitis, but it
has limitations, particularly when acid-fast bacilli cannot be found on smears. A recent
report describes the use of polymerase chain reaction for the identification of
mycobacterium tuberculosis DNA sequences. After the cytologic examination failed to
identify acid-fast bacilli, the remainder of the fine-needle aspirate was assessed using
polymerase chain reaction. This approach significantly increased the diagnostic accuracy
in their patient series and avoided the need for open biopsy of the cervical nodes (13). A
similar study emphasized the speed and accuracy of diagnosis that can be achieved using
a new DNA probe (14).
Isoniazid plus rifampin daily for 9 to 12 months is the regimen most often suggested.
Lymph node excisions en bloc are necessary for fluctuant or chronically draining nodes.
Mastoidectomy should be reserved for concurrent mastoiditis (12).
Actinomycosis
Actinomycosis is a granulomatous infection caused by anaerobic or microaerophilic
Actinomyces species. Infection may follow dental manipulation or trauma (10).
Actinomycosis may occur virtually anywhere in the head and neck, although a palpable
mass is the most common head and neck finding. Sixty-one percent of patients have
visible sinus tracts, and 40% have lymphadenopathy. Concurrent dental, sinus, and
perimandibular disease is common. A characteristic purplish discoloration of the
overlying skin may be seen in some patients. Granuloma formation and frank suppuration
of the larynx also have been reported (23).
Sulfur granules are seen on histologic examination (Fig. 15.4). Diagnosis is confirmed by
culture for 1 to 2 weeks in thioglycollate broth with a CO
2
atmosphere. Paronex and
facial films should also be obtained (10).

FIGURE 15.4. Actinomycosis. Tonsil exhibits colonies
of Actinomyces organisms in the crypts (hematoxylin &
eosin stain; original magnification, 10).



Actinomycosis has been reported as a rare complication after head and neck cancer
surgery, probably on the basis of the prevalence of Actinomyces species as a contaminant
(15).
Treatment is by surgical debridement plus aqueous penicillin G administered
intravenously for 2 to 6 weeks. Penicillin-allergic patients respond well to tetracycline or
erythromycin (10).
Syphilis
Treponema pallidum is the causative organism of syphilis. The multiple manifestations in
the head and neck depend on the stage of the disease. Table 15.9 lists the areas of
involvement by stage (16).

TABLE 15.9. HEAD AND NECK
MANIFESTATIONS OF SYPHILIS



Diagnosis is established by dark-field examination. Histologic examination, although not
pathognomonic for syphilis, reveals a dense chronic inflammatory infiltrate with an
abundance of plasma cells (Fig. 15.5). The results of the fluorescent treponemal
antibody-absorption test are positive whether the patient has been treated or untreated.
The Venereal Disease Research Laboratories test is used for screening, and if the results
of this testing are positive, the test is repeated. If they are still positive, a fluorescent
treponemal antibody-absorption test is obtained.

FIGURE 15.5. Syphilis. The skin of the neck shows
typical, chronic, dense inflammatory infiltrate with
abundant plasma cells (hematoxylin & eosin stain;
original magnification, 40).



Penicillin is the treatment of choice. Steroids are used for improvement of hearing and
reduction of vestibular symptoms (16).
Anthrax
Anthrax is caused by the gram-positive rod, Bacillus anthracis, through direct contact
with infected animals or material. Ninety-five percent of patients present with a small
papule that progresses into a painless necrotic ulcer with surrounding edema, and there
may be regional lymphadenopathy. Diagnosis is made by Gram stain and culture.
Treatment is with penicillin G (12).
Tularemia
Tularemia is caused by the gram-negative pleomorphic rod, Francisella tularensis. The
natural reservoir includes ticks, rabbits, and deer, and it spreads by direct contact. The
patient subsequently exhibits photophobia, decreased visual acuity, and cervical and
preauricular lymphadenopathy. Exudative pharyngitis also may be present. Diagnosis is
confirmed with a serum agglutination test. Patients are treated with streptomycin (10).
Granuloma Inguinale
Granuloma inguinale is caused by Calymmatobacterium granulomatis via sexual
transmission. The most common nongenital site is the oral cavity. A lesion with extensive
scarring and contracture may be seen. Diagnosis is established by culture. Treatment
consists of tetracycline, ampicillin, or sulfamethoxazole-trimethoprim.
Fungal Infections
Histoplasmosis
Histoplasma capsulatum is the causative organism of histoplasmosis. This entity most
commonly occurs in the Ohio and Mississippi river valleys. The organism is spread by
airborne transmission. Manifestations may be considered primary or chronic pulmonary
infection and progressive disseminated infection. Most infections are subclinical and
have benign clinical courses, but patients at the extremes of age or who are
immunocompromised (e.g., HIV infection) get the progressive disseminated form, which
consists of granulomatous lesions of the lips, gingiva, tongue, pharynx, and larynx. These
lesions show firm, slowly enlarging, painful ulcers with heaped-up edges or a verrucous
appearance and sometimes mimic carcinoma or tuberculosis. Sore throat, painful
mastication, hoarseness, gingival irritation, dysphagia, and weight loss may result.
Oropharyngeal involvement is seen in 40% to 75% of adults and 18% of children. A
swab specimen from the center of the ulcer, with growth on Sabouraud medium, verifies
the diagnosis. Amphotericin B is the treatment of choice (17,18).
Blastomycosis
The causative organism of blastomycosis is Blastomyces dermatitidis, which is
contracted by airborne transmission. Manifestations may range from the patient being
asymptomatic to having acute pneumonitis with disseminated infection involving the
skin, bones, and genitourinary system. Lesions exhibit proliferative verrucous growth
with scarring. A common triad consists of cutaneous disease, pulmonary involvement,
and constitutional symptoms. Oropharyngeal and laryngeal involvement is much less
common than in histoplasmosis. Diagnosis is confirmed by sputum culture on Sabouraud
medium and by microscopic examination of skin scrapings. Amphotericin B is the
treatment of choice (19).
Coccidioidomycosis
Coccidioides immitis, a fungus endemic in the San Joaquin Valley of California, causes
coccidioidomycosis. Manifestations in the head and neck are rare but may involve the
skin, mucous membranes, thyroid, eyes, trachea, salivary glands, and epiglottis. Lesions
present as nodules or erosions. Diagnosis is established by a skin test and complement
fixation. Patients are treated with amphotericin B (20).
Paracoccidioidomycosis, also called South American blastomycosis, is a disease found
originally in South America but now being reported in all areas of the world. It is rare in
healthy adults but is a threat to immunocompromised patients. Fluconazole at a dosage of
200 to 400 mg daily appears to be the most effective therapy (21).
Candidiasis
Patients who are immunocompromised or who have recently been on antibiotic therapy
are predisposed to infection by Candida albicans. The classic presentation is that of
creamy white patches of pseudomembrane, with resultant odynophagia, dysphagia,
angular cheilitis, and laryngitis. Diagnosis is established by clinical examination and
culture on Sabouraud medium (Fig. 15.6). Nystatin or ketoconazole may be used for
treatment. Amphotericin B is reserved for severely immunocompromised patients or
those with septic progression.

FIGURE 15.6. Candida albicans. Esophageal biopsy
shows budding yeast and pseudohyphae (Gomori's
methenamine silver stain; original magnification, 40).



Rhinosporidiosis
Rhinosporidium seeberi, especially prominent in Southern India and Sri Lanka, is
responsible for the strawberry lesions of rhinosporidiosis. The characteristically
indolent, painless, warty excrescences that are erythematous, friable, and polypoid occur
on the nasal, palatal, and conjunctival mucous membranes. Treatment is by excision.
Phycomycosis
Phycomycosis, a general term used to describe infection by Mucor, Rhizopus, or Absidia,
occurs almost exclusively in immunocompromised hosts. Facial pain is the most common
symptom, but fever, bloody rhinorrhea, facial swelling, edema, and sinus tenderness are
also common. Progression to proptosis, visual loss, cranial nerve palsies, and obtundation
is the rule. A black necrotic eschar on mucous membranes, although not pathognomonic,
is commonly seen. Diagnosis is confirmed by demonstration of sparsely septate hyphae
by biopsy (Fig. 15.7). A CT is used to assess the extent of involvement. Immediate
administration of amphotericin B and urgent aggressive surgical debridement are
essential for this life-threatening process.

FIGURE 15.7. Mucomycosis. A maxillary sinus
specimen shows vessel invasion and sparsely septate
broad hyphae with obtuse angle branching (hematoxylin
& eosin stain; original magnification, 10).



Cryptococcosis
Immunosuppression is a predisposing factor for the pathogenic fungus, Cryptococcus
neoformans. Manifestations in the head and neck are rare but include membranous
nasopharyngitis, meningitis, and hearing loss. Diagnosis is confirmed by demonstration
of fluorescent antibody. Patients are treated with amphotericin B.
Aspergillosis
Aspergillosis, caused by Aspergillus fumigatus, may be classified as allergic,
noninvasive, or invasive. The invasive form usually occurs in an immunocompromised
host. Thick, tenacious, dark secretions with calcification seen on CTs are common in all
forms. The noninvasive form involves a single sinus. Facial hypesthesia,
ophthalmoplegia, proptosis, and visual loss with concurrent bony destruction of the
sinuses seen on CTs occur in the invasive form. Aspergillosis may be differentiated from
phycomycosis by microscopic examination (i.e., septate, bifurcating hyphae with
Aspergillus) and culture. Treatment consists of surgery and, if the disease is invasive,
administration of amphotericin B.
Invasive aspergillosis and fulminant aspergillosis are rare and highly fatal forms of the
disease even after surgical intervention and postoperative amphotericin B. A recent report
of a patient with skull base invasion managed successfully with partial surgical excision
followed with combined therapy with liposomal amphotericin B and itraconazole
provides some hope for better results in the future (22).
Parasitic Infections
Leishmaniasis
Sandfly bites are responsible for the transmission of several species of Leishmania, which
cause leishmaniasis. Lesions may be cutaneous or mucocutaneous. The cutaneous form
most commonly occurs on the extremities, although the head and neck may be affected.
Papules that progress to ulceration and encrustation are characteristic. Mucocutaneous
leishmaniasis, also called espundia, exhibits an initial lesion on the extremity, with
bloodborne spread to the oral cavity and oropharynx. Months or years later, progressive
inflammation and destruction of the soft tissues of the mouth and nose may occur.
Diagnosis of both forms is established by biopsy. Patients are treated with pentostam.
Myiasis
Myiasis, a condition caused by infestation of the body by maggots and transmitted by the
screwworm fly, may be nonfuruncular or furuncular. The nasopharynx in the former and
the skin in the latter form are the usual sites of involvement. Diagnosis is made by
microscopic examination. Treatment consists of surgical debridement.
Toxoplasmosis
Infection with Toxoplasma gondii occurs by ingestion of oocyst-containing cat feces or
infected poorly cooked lamb or pork. Although most patients are asymptomatic,
clinically overt disease may manifest in almost any organ, including the central nervous
system. Diagnosis is confirmed by IgM and a fourfold increase in IgG in the acute phase.
Pyrimethamine plus trisulfapyrimidines is the treatment regimen of choice.
TRAUMA-INDUCED DISORDERS
Intubation Granuloma
Granulomas from intubation almost invariably involve the vocal processes of the
arytenoids. The initial insult progresses from a contact ulcer to a granuloma to a
pedunculated polyp. Symptoms of hoarseness and foreign-body sensation predominate.
Antibiotics are given for secondary infection, voice rest is advised, and the patient is
observed. If the lesion has become pedunculated, surgical excision is warranted.
Teflon Granuloma
About 2% to 3% of patients who receive Teflon injections for treatment of unilateral true
vocal cord paralysis get initial vocal improvement only to develop increasing dysphonia
or even airway obstruction months or years after the injection. This problem is believed
to be due to an overzealous granulomatous response to Teflon that causes excessive vocal
cord bulk and malposition with resulting dysphoria. Treatment may include endoscopic
removal of the granulation tissue and laser vaporization of the Teflon (23).
Reparative Granuloma
The cause of reparative granuloma is unknown, but it is probably secondary to local
trauma, such as tooth removal. The peripheral form is a sessile or pedunculated mucosa-
covered reddish or bluish mass arising from the gingiva or alveolar mucosa, and it is most
common on the anterior mandible. The central form is endosteal, usually anterior to the
first molar in the mandible. Radiographically, the lesion appears as a lytic, expansile,
unilocular cavity with well-demarcated nonsclerotic margins and a bony cortex, which is
thinned but intact. Treatment consists of curettage.
Pyogenic Granuloma
Pyogenic granuloma is a nonspecific term for granulation tissue formed in response to
minor trauma with secondary infection. The lesion, which is elevated, pedunculated, or
sessile, smooth or verrucal, painless, and soft, occurs most often on the gingiva. Simple
excision usually suffices. Lobular capillary hemangioma is also referred to as pyogenic
granuloma.
ACKNOWLEDGMENTS
We thank Dr. Druhv A. Kumar, Assistant Professor of Pathology, The University of
Texas Medical Branch, for his assistance in obtaining the photomicrographs contained in
this chapter.

HIGHLIGHTS
A thorough history, physical examination, and laboratory
workup are crucial before initiating medical, surgical, or
radiotherapeutic intervention.
BFH is characterized histologically by a biphasic cell
population of fibroblasts and histiocytes with spindle-shaped
cells with elongated nuclei arranged in a storiform pattern.
Polymorphic reticulosis and lymphomatoid granulomatosis are
treated with radiotherapy.
Cervical lymphadenopathy is the most common head and neck
manifestation of sarcoidosis.
Both necrotizing granulomas and necrotizing vasculitis must be
present to confirm the diagnosis of Wegener granulomatosis,
which is treated with prednisone and cyclophosphamide.
Cholesterol granuloma is isodense to brain on a CT;
cholesteatoma is isodense to cerebrospinal fluid.
Cat-scratch disease may be diagnosed by demonstration of
intracellular gram-negative nonacid-fast bacilli, R. henselae,
using Warthin-Starry silver stain of a fine-needle aspirate or
incisional biopsy specimen; R. henselae is the same agent that
causes bacillary angiomatosis.
Corneal ulceration is the most common head and neck
manifestation of nontuberculous mycobacteria; second most
common is cervical lymphadenopathy that is unilateral, adheres
to overlying skin, and arises in the preauricular, submandibular,
and anterior cervical nodes.
Cervical lymphadenitis, frequently involving the posterior
triangles, is the most common head and neck manifestation of
tuberculosis. Ninety-eight percent of patients with cervical
lymphadenopathy secondary to M. tuberculosis have positive
purified protein derivatives.
Intubation granulomas most often arise on the vocal process of
the arytenoid. Progression from contact ulcer to granuloma to
sessile or pedunculated polyp may occur. Surgical excision is
warranted after the lesion has become pedunculated.
Dysphonia can occur months to years after Teflon injection due
to excessive granulomatous response at the Teflon site.
Reparative granuloma is considered to be secondary to local
trauma; a sessile or pedunculated mucosa-covered mass arising
from the gingiva or alveolar mucosa, most often on the anterior
mandible, is characteristic.
CHAPTER REFERENCES
1. Nolph MK, Luikin GA. Histiocytosis X. Otolaryngol Clin North Am 1982;15:635.
2. Bielamowicz S, Daur MS, Chang B, Zimmerman MC. Noncutaneous benign fibrous histiocytoma
of the head and neck. Otolaryngol Head Neck Surg 1995;113:140146.
3. Lazarus AA. Sarcoidosis. Otolaryngol Clin North Am 1982;15:621633.
4. Kornblut AD. Forward to the Symposium on Granulomatous Disorders of the Head and Neck.
Otolaryngol Clin North Am 1982;15:471.
5. Specks U, DeRemee RA. Granulomatous vasculitis (Wegener's granulomatosis and Churg-Strauss
syndrome). Rheum Dis Clin North Am 1990;16:377396.
6. McDonald TJ. Manifestations of systemic disease. In: Cummings CW, et al., eds. Otolaryngology-
head and neck surgery. St. Louis, MO: Mosby-Year Book, 1993.
7. Pisetsky DS. Systemic lupus erythematosus. Med Clin North Am 1986;70:337353.
8. Rosenberg RA, et al. Cholesteatoma vs. cholesterol granuloma of the petrous apex. Otolaryngol
Head Neck Surg 1986;94:322327.
9. Batsakis JG, Ro JY, Frauenhoffer EE. Bacillary angiomatosis. Ann Otol Rhinol Laryngol
1995;104:668672.
10. Richtsmeier WJ, Johns ME. Bacterial causes of granulomatous diseases. Otolaryngol Clin North
Am 1982;15:473492.
11. Brazin SA. Leprosy (Hansen's disease). Otolaryngol Clin North Am 1982;15:597611.
12. Waldman RH. Tuberculosis and the atypical mycobacteria. Otolaryngol Clin North Am
1982;15:581596.
13. Baek CH, Kim SI, Ko YH, et al. Polymerase chain reaction detection of mycobacterium
tuberculosis from fine-needle aspirate for the diagnosis of cervical tuberculous lymphadenitis.
Laryngoscope 2000;110:3034.
14. Yokoyama J, Shiga K, Saijo S, et al. Rapid diagnosis of cervical tuberculous lymphadenitis by
application of DNA probe. Otolaryngol Head Neck Surg 1999;121:501504.
15. Zitsch RP III, Bothwell M. Actinomycosis: a potential complication of head and neck surgery. Am
J Otolaryngol 1999;20:260262.
16. Martinez SA, Mouney DF. Treponemal infections of the head and neck. Otolaryngol Clin North
Am 1982;15:613620.
17. Gerber ME, et al. Histoplasmosis: the otolaryngologist's perspective. Laryngoscope
1995;105:919923.
18. Economopoulou P, Laskaris G, Kittas C. Oral histoplasmosis as an indicator of HIV infection.
Oral Surg Oral Med Oral Pathol Oral Radiol Endocontics 1998;86:203206.
19. Bergman KR, Sorensen P, Sinha C. Disseminated blastomycosis presenting as a neck mass.
Otolaryngol Head Neck Surg 2000;122:270271.
20. Polesky A, Kirsch CM, Snyder LS, et al. Airway coccidioidomycosis: report of cases and review.
Clin Infect Dis 1999;28:12731280.
21. Sant'Anna GD, Mauri M, Arrarte JL, et al. Laryngeal manifestations of paracoccidioidomycosis
(South American blastomycosis). Arch Otolaryngol Head Neck Surg 1999;125:13751378.
22. Streppel M, Bachmann G, Arnold G, et al. Successful treatment of an invasive aspergillosis of the
skull base and paranasal sinuses with liposomal amphotericin B and itraconazole. Ann Otol Rhinol
Laryngol 1999;108:205207.
23. Varvares MA, Montgomery WW, Hillman RE. Teflon granuloma of the larynx: etiology,
pathophysiology, and management. Ann Otol Rhinol Laryngol 1995;104:511515.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

16 DYNAMICS OF WOUND HEALING
Head & Neck SurgeryOtolaryngology
16




DYNAMICS OF WOUND HEALING
DAVID J. TERRIS

D.J. Terris: Department of Otolaryngology/Head and Neck Surgery, Stanford University, Stanford,
California.


Historical Perspective
Normal Wound-Healing Process
Coagulation Phase
Inflammatory Phase
Fibroplasia Phase
Remodeling Phase
Collagen Metabolism and Wound Healing
Collagen Synthesis
Collagen Lysis
Cytokines (Growth Factors) in Wound Healing
Transforming Growth Factors
Epidermal Growth Factor
Platelet-derived Growth Factor
Fibroblast Growth Factors
Growth Hormone
Factors That May Impede Wound Healing
Radiation
Steroids
Nutrition
Age
Manipulation of Wound Healing
Cytokine Therapy
Tissue Adhesives
Fetal Wound Healing
Special Circumstances in Wound Healing
Nerve Regeneration
Bone Healing
Mucosal Wound Healing
Healing of Skin Grafts
Keloids and Hypertrophic Scars
Future of Wound Healing
Chapter References
The entire field of surgery, and much of nonsurgical medicine, relies on normal
functioning of the wound-healing process. To ensure this normal functioning, exploit the
mechanisms involved, and correct malfunctioning of this system, we must understand the
complex interactions involved in wound healing at a systemic, cellular, and molecular
level. Recent discoveries in the precise mechanism of these molecular interactions will
undoubtedly prompt a revolution in wound management.
HISTORICAL PERSPECTIVE
An interest in the concepts of wound healing dates at least to 1700 B.C., when several
case reports documented in the Smith Papyrus described the management of wounds.
Evidence exists that the ancient physicians of Egypt, India, and Europe proposed gentle
methods of managing wounds. They advocated the removal of foreign bodies, suturing,
and coverage of wounds with clean materials. The earliest sutures were probably the
mandibles of soldier ants, used by the Sumerians to close wounds.
This passive approach toward wound healing evolved over many centuries into a more
aggressive attitude, in which surgeons sought to apply burning oil, scalding water, and
even hot cautery to wounds to enhance the healing process. During the same time period,
there was a failure to recognize the dangers associated with infection. The presence of
uncontrolled infection was even thought to be advantageous, as described by Sir Clifford
Allbutt: There is nothing so wholesome in a wound as a good discharge of laudable
pus. Other substances used in attempts to modulate wound healing included animal
grease, honey, lint, meat, and clay.
It was not until the seventeenth century, when Ambroise Pare, a French Army surgeon,
determined that wounds treated gently healed more readily, that the modern
understanding of the nature of wound healing was born. The importance of this careful
handling of tissue, including gentle surgical and postsurgical technique, was advocated
by the teachings of John Hunter, William Stewart Halsted, and Alexis Carrel.
As is frequently the case, military conflicts also assisted in the learning process; the early
appreciation of the power of wound contraction was described and implemented during
the Civil War. The practice of leaving amputation wounds open began because closure of
extremity amputations often led to disastrous results, including sepsis and death. The
healing of these open amputations required up to several months, but even very large
wounds would contract sufficiently to result in a closed stump. The treatment of open
wounds with Dakin's solution became popular during World War I. Limitations of time,
materials, and personnel in the battlefield precluded the ability to perform surgical
debridement in many instances, and chemical debridement became an accepted
alternative. During the second World War, the practice of delayed closure of
contaminated wounds was developed to help prevent infection and to hasten the wound-
healing process.
The last two decades has seen an explosion in the knowledge of the healing process
among molecular biologists, with particular advances made in fetal wound healing and
cytokines (growth factors). Equally important, however, is the evolution of widespread
understanding and appreciation of the importance of healing mechanisms among
practicing surgeons.
NORMAL WOUND-HEALING PROCESS
There are three basic types of wound repair after injury: primary healing (Fig. 16.1A), in
which the wound edges are brought together by means of sutures, staples, tape, or other
devices; delayed primary healing (Fig. 16.1B), in which a wound (usually contaminated
or frankly infected) is allowed to remain open for several days until the bacterial count is
lowered, at which time the wound is closed (either by approximation of the edges, or
placement of a graft); and secondary or spontaneous wound healing (Fig. 16.1C), in
which the wound is allowed to heal by a combination of contraction and epithelialization.

FIGURE 16.1. Primary wound healing (A) in which the
wound edges are brought together using sutures, staples,
or tape. Delayed primary healing (B) occurs when a
wound is allowed to remain open (usually because of
contamination or infection) and is subsequently closed
when the bacterial count drops. Secondary or
spontaneous wound healing (C) occurs when a wound
is allowed to remain open and heals secondarily by a
combination of contraction and epithelialization. (From Cohen IK, Diegelmann RF,
Crossland MC. Wound care and healing. In: Schwartz SI, Shires GT, Spencer FC, eds.
Principles of surgery. New York: McGraw-Hill, 1994, with permission.)



For simplicity of presentation and understanding, the mechanisms necessary for normal
wound healing are discussed in four distinct phases (Fig. 16.2). However, it should be
understood that wound healing is a dynamic interplay of numerous molecular and cellular
cascades that occur simultaneously in symphony rather than as a consecutive sequence of
events (Fig. 16.3). After a description of these phases, particular attention is focused on
two areas that deserve additional emphasis: collagen metabolism and the activity of
cytokines. The final remarks address the wound healing of specific tissues and factors
that enhance or retard wound healing.

FIGURE 16.2. Summary of the discrete phases involved
in tissue repair, including many of the cells and cytokines
involved in the process. (From Cohen IK, Diegelmann
RF, Crossland MC. Wound care and healing. In:
Schwartz SI, Shires GT, Spencer FC, eds. Principles of
surgery. New York: McGraw-Hill, 1994, with
permission.)



FIGURE 16.3. Overview of the dynamic and complex
interactions that occur in symphony during wound
healing. (From Feinberg SE, Larson PE. Healing of
traumatic injuries. In: Fonseca RJ, Walker RV, eds. Oral
and maxillofacial trauma. Philadelphia: W.B. Saunders,
1991, with permission.)



Coagulation Phase
Injury causes hemorrhage with exposure of platelets to the thrombogenic subendothelial
connective tissue. This activates the platelets, resulting in an almost immediate release of
numerous vasoactive substances that cause vasoconstriction (serotonin via S
2
receptors
and catecholamines). The transient (5 to 10 minutes) vasoconstriction helps to control
bleeding and is followed by the formation of a primary hemostatic plug as the platelets
aggregate. The remaining vasoactive substances (serotonin via S
1
receptors, bradykinin,
and histamine) cause vasodilation of small vessels (predominantly venules), leading to
the transit of plasma proteins, red blood cells, and leukocytes into the wound.
Platelets are critical elements of this early response, not only because of their hemostatic
function but also because of the concurrent release of numerous cytokines that are
necessary to initiate the cascade of events that follow. The clotting cascade depends
heavily on the activation of platelets, which causes the release of stored products,
initiating both the intrinsic coagulation pathway (via contact activation of factor XII, or
Hageman factor) and the extrinsic coagulation pathway (via activation of factor VII by
tissue factor) (1). The fibrin that is produced not only contributes to hemostasis but also
forms a matrix across which fibroblasts, leukocytes, and keratinocytes subsequently
migrate.
Inflammatory Phase
An intense inflammatory reaction begins simultaneously with the coagulation phase. This
inflammation is marked by a suffusive infiltration of leukocytes, which migrate through
vessel walls by a process known as diapedesis. Polymorphonuclear leukocytes
predominate during the first 24 to 48 hours. These motile leukocytes scavenge and engulf
cellular debris, foreign bodies, and any other byproducts of the wounding event. The
white cell population in the wound then shifts such that monocytes predominate. The
monocytes mature into macrophages, which contribute to the continued cellular
debridement.
In a typically clean surgical wound, this inflammatory reaction subsides over a period of
several days; it can, however, continue for weeks in a contaminated posttraumatic wound.
Fibroplasia Phase
Tissue restoration occurs during the period of fibroplasia (proliferation and accumulation
of fibroblasts and their products), also known as the proliferative phase. Through a
variety of mechanisms, including cytokine activity, fibroblasts are attracted to the wound.
These fibroblasts are responsible for the synthesis of the collagen from which the wound
derives its strength, and therefore these cells are critical to normal wound healing. The
fibroblasts migrate into the wound after approximately 48 to 72 hours and are derived
from local undifferentiated mesenchymal cells present in the extravascular tissues. At the
same time, endothelial budding occurs (angiogenesis), resulting in newly formed
capillaries, which deliver nutrients and oxygen to the wound bed. These abundant
capillaries provide the wound with a characteristic beefy-red appearance, known as
granulation tissue. This name was coined by early physicians who were impressed with
the finely granular nature of the healing surface.
The fibroblasts are very active at this point, producing collagen, mucopolysaccharides,
and elastin. The mature scar is comprised primarily of collagen fibers embedded in an
extracellular matrix, the components of which are listed in Table 16.1.

TABLE 16.1. MAJOR COMPONENTS OF
EXTRACELLULAR MATRIX



Remodeling Phase
In the remodeling or maturation phase, the inflammatory response has resolved,
angiogenesis diminishes, and the intense fibroplasia begins to subside. The process of
collagen lysis, which is perpetual, reaches equilibrium with the level of collagen
synthesis. This dynamic balance between collagen synthesis and lysis is responsible for
the maturation of the wound.
The net gain in tensile strength undergoes an exponential growth phase that plateaus in a
prolonged period of gradually increasing wound strength. This is reflected in classic
studies using a rat model, depicted in Fig. 16.4. However, the scar tissue never regains
the breaking strength of normal skin, reaching a maximum strength of approximately
80% of unwounded skin.

FIGURE 16.4. The increase in the breaking strength of a
healing experimental wound over time is shown in
kilograms and as a percent of the strength of comparable
unwounded skin. Note that the maximum strength
achieved is approximately 80% of the unwounded skin.
(From Levenson SM, et al. The healing of rat skin
wounds. Ann Surg 1965;161:293, with permission.)



Wounds that are left open to heal by secondary intention rely heavily on epithelialization
and wound contraction. Epithelialization begins within 24 hours after wounding by
migration of basal keratinocytes either from the edges of the wound or from within the
wound if they are still intact. This migration, as well as the concomitant proliferation of
keratinocytes, is stimulated by several cytokines. Another proposed stimulant for
keratinocyte migration and proliferation is the free-edge effect, whereby these activities
are precipitated by the absence of adjacent cells at the margin of the wound.
The second important element of secondary healing, which is often exploited by surgeons
but can be deleterious, is wound contraction (Fig. 16.5). This process occurs by the
stretching of surrounding skin to close the defect rather than by production of new skin.
The mechanism of this contraction remains poorly understood. There is evidence to
support the role of a specialized fibroblast called the myofibroblast, which contains
abundant actinomyosin and behaves like smooth muscle. The granulation tissue of
contracting wounds contains as much actinomyosin as the uterus, for instance, and these
myofibroblasts are capable of causing contraction of granulation tissue in vitro. Wound
contraction is inhibited when anti-smooth muscle agents are applied topically. Additional
studies, however, suggest that collagen and the ground substance may contribute to the
process of wound contraction. It may be that the combination of both a specialized cell
(the myofibroblast) and a material susceptible to contraction (the ground substance) is
necessary for contraction to occur.

FIGURE 16.5. A large area of left neck skin tissue
necrosis (A) in a patient who underwent salvage surgery
of an advanced tonsil cancer after failed chemoradiation.
After debridement, a granulation bed forms with
simultaneous wound contraction (B). The resultant
wound (after closure with a skin graft) is substantially
smaller than the original defect (C). (From Yao M, Terris
DJ. Surgical management of radiation-injured tissues of
the head and neck. Front Radiat Ther Oncol 1999;32:4962, with permission.)



When the process of contraction occurs in vital areas where there is little or no redundant
skin, the net effect may be detrimental. Examples include contraction of a lower eyelid
defect that produces an ectropion or of a defect of the palmar surface of the hand to cause
a flexion contracture. The best method for prevention of contraction is placement of a
skin flap. Full-thickness grafts are nearly as effective as skin flaps, but split-thickness
skin grafts provide only slight inhibition of contracture.
Open wounds heal more quickly when they are kept moist, and they should therefore not
be left open to air. A scab (comprised of dried or denatured proteins and dead cells) may
form and should be left intact, because wound healing will continue efficiently beneath it.
When an eschar forms (representing necrotic tissue from burns or flap loss, for instance)
it may inhibit healing and should be debrided gently.
COLLAGEN METABOLISM AND WOUND HEALING
The extracellular matrix consists of fibrous structural proteins (collagen and elastin) and
an interstitial matrix composed of adhesive glycoproteins (fibronectin and laminin)
embedded in the ground substance (an amorphous gel containing proteoglycans and
glycosaminoglycans) (Table 16.1). Although the ground substance contributes to the
formation of scar tissue, the strength of the wound is derived primarily from the collagen
fibers. At least 13 distinct forms of collagen have been described, which are coded for by
25 different genes (2); the five major types are listed in Table 16.2. A simplistic depiction
of the very complex process of collagen synthesis is represented in Fig. 16.6.

TABLE 16.2. FIVE MAJOR TYPES OF
COLLAGEN



FIGURE 16.6. Simplistic representation of the complex
events involved in the production of collagen. A:
Fibroblasts, actively involved in protein synthesis. B:
Tropocollagen production of triple helices. C: Collagen
filament, demonstrating intermolecular bonding. D:
Aggregation of collagen filaments into collagen fibrils.
E: Collagen fiber. F: Mature collagen fibers arranged in
connective tissue. Inset: Molecular structure of type 1
procollagen molecule, demonstrating extension peptides at both the amino- and carboxy-
terminal ends. The basic molecule is composed of three chains in a helical complex.
(From Das SK. Wound healing, operative incisions, and skin grafts. In: Hardy JD, ed.
Hardy's textbook of surgery. Philadelphia: J.B. Lippincott, 1988; and Cohen IK,
Diegelmann RF, Crossland MC. Wound care and healing. In: Schwartz SI, Shires GT,
Spencer FC, eds. Principles of surgery. New York: McGraw-Hill, 1994, with
permission.)



Collagen Synthesis
Collagen is the most common protein in the animal world and is the principal component
of human connective tissue, making up nearly 30% of the total body protein. It is an
extracellular protein that is manufactured intracellularly by fibroblasts. During wound
healing, the transcription of procollagen mRNA is upregulated. The mRNA is extensively
modified and then translated on the ribosomes of the rough endoplasmic reticulum; the
procollagen protein then passes through the Golgi apparatus into the extracellular space.
In the extracellular space, the procollagen undergoes enzymatic cleavage of its nonhelical
ends and then spontaneously assembles into fibers (2). Collagen is unique because it
contains the amino acids hydroxyproline and hydroxylysine; the hydroxylation occurs
after the proline and lysine are incorporated into the collagen chain. This requires specific
enzymes (prolyl and lysyl hydroxylase) and several cofactors and substrates, including
ascorbic acid, iron, and -ketoglutarate. Without the hydroxylation of proline and lysine,
the collagen molecule is unstable and offers little resistance to enzymatic degradation.
This results in a compromise of collagen production and insufficient wound strength, as
occurs in patients with vitamin C deficiency or scurvy. The fact that fresh fruit is able to
prevent this disease was appreciated by the British Navy at the turn of the century; thus,
British sailors earned the name limeys, because they were required to travel with limes
and other citrus fruits when away at sea for long periods of time. Other posttranslational
steps in collagen synthesis include glycosylation by the addition of galactose and glucose
to hydroxylysine residues, which is catalyzed by galactosyltransferase and
glucosyltransferase, respectively (2).
In addition to its two unique amino acids, collagen is also notable for the arrangement of
three -peptide chains in a right-handed triple helix with glycine in every third position
along the peptide chain. The triple helical configuration of collagen is achieved by proper
alignment and formation of disulfide bridges between the carboxy-terminal ends of the
three -peptide chains, with intramolecular hydrogen bonding between the chains to
maintain the helical structure. Triple collagen is soluble in water and must be cross-linked
to render it insoluble; this cross-linkage provides tensile strength. The nature and degree
of cross-linking imparts the collagen with its tissue-specific characteristics. Numerous
types of cross-linking are possible and occur in two broad categories: intramolecular and
intermolecular. The first step in cross-linking is the conversion of peptide-bound lysine
and hydroxylysine residues to aldehydes by means of the enzyme lysyl oxidase. This
oxidative deamination yields the corresponding semialdehydes, allysine and
hydroxyallysine. This step may be inhibited by administration of (-aminopropionitrile,
D-penicillamine, and isoniazid. These substances have been used with limited success
experimentally in an effort to prevent excessive collagen formation. Intermolecular
disulfide bonds are important cross-links because they may provide a rapid and efficient
method of cross-linking fibers in proliferating tissues, such as healing wounds (2).
The inflammatory response to injury, and the proliferation of fibrosis that follows, are
modulated by a number of variables, including cytokine activity. Several cytokines,
transforming growth factor (TGF)-, interleukin-1, and tumor necrosis factor-, each
contributes to an increase in the steady-state production of collagen (2). The role of
cytokines in wound healing is addressed in greater detail below.
Collagen Lysis
The production of collagen, as with many other physiologic functions, exists as a
homeostatic and dynamic process. Throughout the body, collagen is constantly being
produced and constantly being degraded. When increased collagen deposition is required,
as in a healing wound, the balance tips in favor of production. This is represented by the
fibroplasia phase. In the remodeling phase, the balance tips in favor of collagen lysis, and
the scar softens and matures. Collagen is remarkably resistant to degradation and remains
insoluble in the face of a wide range of proteases. In fact, a specific class of enzymes has
become apparent, whose primary role is to degrade collagen. The activity of these
collagenases is upregulated during periods of wound remodeling, as is intracellular
degradation of newly synthesized collagen. Therefore, there are at least two mechanisms
by which collagen homeostasis can be modulated.
This complex balance of collagen production and degradation is responsible for both the
dramatic early and subtle late changes in wounds and scars. This process unfortunately
remains incompletely understood.
CYTOKINES (GROWTH FACTORS) IN WOUND HEALING
Cytokines are polypeptide signal proteins that are released from local tissues or blood
components and are instrumental in modulating cellular functions, including cell
proliferation, differentiation, tissue regeneration, and wound healing. Unfortunately,
understanding the complex interactions involved with the various cytokines is made even
more difficult because of the confusing nomenclature. Specifically, some cytokines are
named for their cell of origin (e.g., platelet-derived growth factor [PDGF]), whereas
others are named for their target cell (e.g., epidermal growth factor [EGF]). This occurred
in some cases because the factors were named before the major activities were known. In
addition, some cytokines are named for their first reported action (e.g., transforming
growth factor-). Finally, the actions of cytokines may be complex and numerous and
unable to be described by a single name.
The mechanism of action of the cytokines may be through endocrine (secreted by one
population of cells and having distant effects), autocrine (secreted by cells which then are
themselves modulated by the factor), or paracrine (secreted by cells and affecting
neighboring cell populations) activity. Each cytokine binds specific cell surface receptors,
which in turn modulate the activities of second messengers (such as intracellular cAMP).
The cytokines can be divided into two major categories: angiogenic growth factors and
bone morphogenetic proteins. There are four major families of angiogenic growth factors:
transforming growth factor, EGF, PDGF, and fibroblast growth factor (FGF). A summary
of the cytokines known to participate in the wound-healing response is provided in Table
16.3. Although the only U.S. Food and Drug Administration-approved application of
cytokines is the use of PDGF for diabetic ulcers, the wealth of experimental evidence
regarding the value of growth factors in wound healing has brought the field to the brink
of widespread clinical applicability, and some of this progress is indicated below.

TABLE 16.3. CYTOKINES INVOLVED IN WOUND
HEALING



Transforming Growth Factors
The TGF family of cytokines is composed of two parental compounds, TGF- and TGF-
. These two compounds are actually quite distinct; in fact, TGF- is more closely
related to EGF than to TGF-. All the associated factors in this family are important in
the wound-healing process, although TGF- (which occurs as three distinct isoforms)
probably has the most important role and is the most fibrogenic. The TGFs derive their
name from the fact that they are able to transform normal cells into apparently
neoplastic cells. However, they are also known to be mitogenic and chemotactic for
epidermal and endothelial cells. TGF- also stimulates the production of fibronectin,
glycosaminoglycans, and collagen. TGFs are secreted by a variety of cells and tissues,
including platelets, macrophages, keratinocytes, T lymphocytes, and neutrophils. They
exert their effects by binding to receptors, causing activation of the tyrosine kinase
cascade. There is experimental evidence to suggest that TGF- may accelerate wound
healing when applied topically. The beneficial effects imparted by TGF- are realized
with or without the addition of radiation (4). Excessive TGF- levels, however, may
induce pathologic fibrosis. This limitation must be acknowledged as clinical trials are
contemplated.
Epidermal Growth Factor
EGF, a polypeptide of 53 amino acids, manifests a high degree of homology with TGF-
and contributes to collagen formation, granulation tissue development, and enhanced
epithelialization by intracellular effects exerted through the enzyme tyrosine kinase (5).
EGF has a specific impact on wound healing by the stimulation of keratinocyte and
dermal fibroblast division and by the potentiation of both the production and the effects
of other cytokines.
The potential value of EGF in enhancing wound healing was suggested by a prospective,
randomized, double-blind, clinical trial of its effect on the healing of split-thickness skin
graft donor sites (6). Although not every study has found this cytokine to be effective, the
overall results are likely to justify an expanded scope of investigation of this important
cytokine.
Platelet-derived Growth Factor
PDGF is a glycoprotein composed of two chains ( and ) resulting in three different
dimeric forms of PDGF (PDGF-AB, PDGF-AA, and PDGF-BB). As with many of the
other cytokines, interaction with the PDGF receptor results in activation of the tyrosine
kinase enzyme system. Although PDGF derives its name from the original identification
of its source, it is also found in monocytes, macrophages, smooth muscle cells, and
endothelial cells. PDGF has numerous actions, including the promotion of angiogenesis,
mitogenicity for mesenchymal cells (fibroblasts and smooth muscle cells), stimulation of
collagen and matrix formation, and the chemoattraction of neutrophils and macrophages.
It is therefore thought to be an important participant in the early response to injury. PDGF
accelerates the rate of healing of incisional wounds but may require the presence of other
cytokines to perform most effectively. The efficacy of PDGF has already been
demonstrated in prospective randomized studies in which it was topically applied to
nonhealing cutaneous ulcers (7).
Fibroblast Growth Factors
The fibroblast growth factors (FGFs) are a family of at least 19 distinct cytokines. The
original two FGFs described were acidic FGF and basic FGF. There is some overlap in
the binding of the receptors within this family of cytokines (and across other families of
cytokines as well), with variable degrees of reactivity. After binding of the FGF cell
receptors, the tyrosine kinase cascade is activated, resulting in proliferation and migration
of vascular endothelial cells and stimulation of neovascularization (5). Other recognized
activities of FGFs include mitogenicity and chemotaxis for keratinocytes and fibroblasts.
Basic FGF was shown in a human clinical trial to improve wound healing when applied
topically to chronic pressure sores (8).
Growth Hormone
Human growth hormone (GH), a polypeptide of 191 amino acids, is a systemic cytokine
that participates in the wound-healing process. Although a GH receptor has been
identified, there is significant similarity between receptors for several cytokines, and it is
likely that there is substantial overlap in the activity. The GH receptor has been found in
both fibroblasts and normal human skin, suggesting that these are targets for its action.
Although the mechanism of contribution of GH to wound healing is not entirely clear, it
does have the ability to enhance wound collagen content and tensile strength. In addition,
GH is known to have a mitogenic influence on fibroblasts.
Exploitation of the activity of GH in wound healing has been demonstrated both for burn
wound healing and healing of the donor site after split-thickness skin grafting (9).
Although this treatment provides promise for the use of GH, its widespread use in routine
clinical cases must await confirmation of its beneficial effects and evaluation of cost
effectiveness.
Because the half-lives of cytokines are generally hours or less, sustained-release delivery
is desirable. Most efforts to produce a prolonged effect have thus far been unsuccessful.
A notable exception has been in the field of neurotrophic growth factors, where both
brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor have been
successfully delivered both in an osmotic pump and cross-linked to collagen tubules to
enhance nerve regeneration in experimental models (10,11). Although many investigators
have focused on local delivery of cytokines, the systemic administration of several
cytokines, including GH, EGF, FGFs, PDGF, and TGF-, and neurotrophic factors
certainly appears to have the ability to enhance wound healing (5).
In addition to the remaining cytokines listed in Table 16.3, the bone morphogenetic
proteins have emerged as highly specific modulators of bone healing and are discussed in
a subsequent section.
FACTORS THAT MAY IMPEDE WOUND HEALING
Some of the numerous conditions that may impair the normal process of wound healing
are listed in Table 16.4. Those most commonly encountered by otolaryngologists/head
and neck surgeons are discussed below.

TABLE 16.4. FACTORS THAT IMPEDE WOUND
HEALING



Radiation
Radiation induces acute, intermediate, and chronic effects on tissues (12). The acute
effects (whose severity is related to the radiation fraction) include a significant reduction
in fibroblast, myofibroblast, and endothelial cell proliferation (which may result in
impaired wound contraction). The intermediate effects are usually manifested between 3
and 6 months after radiation and result in diminished endothelial and connective tissue
proliferation. The late effects (which are related to the total radiation dosage) include
hyalinization of collagen, rupture of elastic fibrils, deposition of fibrinous exudate, and
induction of atypical fibroblasts. Likewise, blood vessels become hyalinized and
sclerotic; this may lead to cerebrovascular disease in patients receiving radiation for head
and neck cancer. The optimal time to operate on patients whose tissues have been
irradiated is after the acute effects have subsided (no less than 3 weeks) but before the
intermediate effects have emerged (no more than 3 months) (12).
The mechanism by which radiation therapy impairs wound healing is not well
understood. Although inhibition of fibroblast proliferation has been implicated, there is
preliminary evidence to suggest that damage to the resident fibroblasts is not as critical as
suppression of the hematopoietic system. Although the net effect is a wound that is
slower to heal, a decrease in the wound contraction may be an effect that can be
exploited.
Several authors have now examined the impact of combination chemoradiation therapies,
so-called organ preservation protocols, on wound healing. Although surgery for salvage
in these patients is considered safe and desirable, there is a growing consensus that the
risk of wound complications (particularly fistulae and flap necrosis) in this patient
population is increased, especially when the pharynx is entered. Of particular concern is
the prolonged time to resolution of fistulae and flap necrosis, up to 7.7 months in one
study (13).
Osteoradionecrosis is one manifestation of poor wound healing after radiation. This
feared complication of oral cavity radiation is difficult to treat and may require surgery,
prolonged courses of intravenous antibiotics, and in some instances hyperbaric oxygen
(12).
Steroids
Numerous studies confirm that steroids administered systemically, locally, or topically
may impair wound healing and/or strength. This suppression of wound healing occurs by
three mechanisms: reduction in leukocyte and monocyte migration and phagocytosis,
which diminishes the inflammatory response; inhibition of keratinocyte and fibroblast
mitosis, which slows reepithelialization; and vasoconstriction, resulting in reduced
oxygen and nutrient delivery to the healing wound. A steroid dose equivalent to at least
10 mg of prednisone per day is required to induce these changes. These effects may be
mitigated by the systemic or topical administration of vitamin A.
Nutrition
Although adequate nutrition is important for normal wound healing, the body has
apparently given wound repair such a high priority that compromise of the normal
processes are only seen with severe nutritional deficiencies. For instance, although low
serum albumin concentrations are associated with an increased risk of wound infection
and dehiscence, protein depletion generally retards healing only when weight loss
exceeds 20% of original body weight.
Most nutritional elements essential to wound repair have been identified because of the
consequences of their deficiency. There are several specific vitamin deficiencies, for
example, which can lead to diminished healing. Vitamin C deficiency (also called scurvy)
prevents the hydroxylation of proline and lysine, for which it is a necessary cofactor.
Production of collagen is therefore significantly reduced, whereas collagen lysis
continues. Not only do new wounds heal poorly, but old healed scars become fragile and
can break down.
Vitamin A deficiency (probably the most common vitamin deficiency in the Western
world) causes impaired collagen synthesis and epithelialization, resulting in reduced
tensile strength and increased susceptibility to infection. Supplementation not only
prevents these effects but may also mitigate the deleterious effects associated with
radiation, steroid therapy, and diabetes mellitus.
Zinc deficiency may lead to retarded wound healing by preventing cell proliferation,
which particularly effects fibroplasia. Although zinc replacement (220 mg three times a
day) is corrective, care should be taken not to provide zinc in the nondeficient state,
because excessive levels may hamper macrophage migration and phagocytosis and
therefore impair wound healing.
In summary, severe malnourishment may lead to compromised wound healing. Under
that circumstance, appropriate nutritional supplementation will restore the normal wound
repair mechanisms. However, most patients will derive no benefit from enhancement of
their baseline nutritional status.
Age
Cell proliferation and metabolic activities decline with age, so that collagen synthesis is
reduced, immune responsiveness is diminished, and reepithelialization and angiogenesis
are delayed compared with younger patients. As a result, the incidence of wound
dehiscence after surgery increases threefold in patients over 60 years of age. This
association has particular importance, because many patients who undergo head and neck
cancer resections fall into that age category. This increased risk of wound complications
is frequently exacerbated when tissues have been irradiated.
MANIPULATION OF WOUND HEALING
In an effort to manipulate wound healing, a number of technologies have been studied,
including ultrasound treatment, ultraviolet A radiation, electrical stimulation, and laser
therapy. Although most of these have shown some degree of promise in animal models,
they remain investigational techniques. Several disciplines in which significant progress
has been made in translating basic science into clinical applicability are described briefly
below.
Cytokine Therapy
Although cytokine treatment may improve the rate and strength of normal wound
healing, a more likely use is to reverse the detrimental effects of conditions like diabetes
mellitus. Such conditions known to impede wound healing may be ameliorated, based on
experimental evidence that GH improves wound healing in malnourished animals treated
with corticosteroids (14). This reversal of the deleterious effects of steroids on wound
healing was achieved with the use of several other cytokines, including TGF-, PDGF,
and insulin-like growth factor-1. Ultimately, a combination of manipulative techniques
may be the preferred tactic, as suggested by evidence that the benefits of pharmacologic
doses of cytokines may be amplified when combined with treatments such as hyperbaric
oxygen.
Tissue Adhesives
Fibrin glues have been in use in otolaryngology for a number of years, but nonhistotoxic
synthetic adhesives have only recently become widely available. The compound 2-octyl
cyanoacrylate has allowed more rapid skin closure with comparable cosmetic results
when compared with suture closure (15). As greater experience is gained with this
substance, the indications for its use will no doubt expand further.
Fetal Wound Healing
It seems natural to understand and ultimately exploit the scarless healing that occurs with
fetal wounds. In fact, the fetal fibroblast has been confirmed to be the primary cell
responsible for such impeccable healing. One study suggested that the cytokine milieu
plays a role in scarless fetal wound healing by finding that the presence of TFG- led to
scarred wounds, whereas this cytokine was absent in fetal scarless wounds (16). Still
others have speculated that there are new as yet uncharacterized factors secreted by these
cells that result in the scarless healing. It is possible that these factors may someday be
identified and genetically engineered and their use may lead to the ultimate goal of
scarless wound healing.
Finally, a time-honored tradition in the management of open wounds is the topical
application of Dakin's solution (0.25% sodium hypochlorite). The chemical debridement
of the wound and antimicrobial activity achieved by this solution were recognized as
early as 1915, when it was introduced by Dakin. Its use was popularized by Nobel Prize
laureate Alexis Carrel during World War I. Despite concern for potential toxicity to
normal tissues, wet-to-dry dressings with Dakin's solution remain a popular alternative to
saline-soaked dressings, particularly for contaminated or necrotic wounds.
SPECIAL CIRCUMSTANCES IN WOUND HEALING
Nerve Regeneration
The healing of nerves comprises a particular area of interest to head and neck surgeons,
because much of head and neck surgery, including oncologic head and neck surgery,
neurotologic surgery, and skull base surgery, places cranial nerves at risk for injury and
the healing of nerves has functional and cosmetic implications. As with other areas of
wound healing, neural regeneration has seen an explosion in the understanding of
mechanisms of repair and the birth of potential for manipulation of this repair process.
Nerve healing occurs as a dynamic complex interplay of several processes and is
modulated by a number of factors. Much of the current appreciation for the complexities
of nerve injuries and healing are a product of the work of Sir Sydney Sunderland, after
whom the classification of nerve injuries is named. His classic volume (17) paved the
way for two decades of intense investigation into the microenvironment of the
regenerating nerve.
Sunderland (17) described three fundamental types of nerve injury: a transient
interruption of nerve conduction without loss of axonal continuity (also called
neuropraxia or conduction block); transection of axons (or conditions leading to loss of
axonal integrity) but with preservation of the endoneurium during Wallerian degeneration
(known also as axonotmesis); and complete disruption of the nerve fiber, with loss of the
normal architecture (neurotmesis). The third level of injury can be further subdivided to
include perineurial disruption (class IV injury) or epineurial transection (class V injury);
all injuries that include neurotmesis may result in aberrant regrowth of axons into the
wrong endoneurial tubes.
The response of the injured nerve in the first 12 to 48 hours includes Wallerian
degeneration (degeneration of the distal axon to the motor endplate and of the proximal
axon to the first node of Ranvier), axonal edema, and retraction of myelin. From 48 to 72
hours, the axons break into twisted fragments, and by the second week after injury, all
traces of the axon are usually lost. The distal nerve fibers can be stimulated for
approximately 72 hours after injury, an essential time frame to consider when
contemplating exploration of traumatic nerve injuries. Macrophages are mobilized to
phagocytize debris along the nerve, and Schwann cells contribute to this activity. The
main role of Schwann cells, however, is to guide regeneration by forming dense cellular
cords (called Bungner's bands) along the site of the degenerating axon. These bands
provide conduits for axons once regeneration ensues.
The duration of the regenerative process varies and may require 6 to 18 months,
depending on the length of the nerve and the site of the lesion. Despite the commonly
quoted regeneration rate of 1 mm/day, this figure varies considerably and can be used
only as a rough estimate. On occasion, there may be very early signs of recovery, thought
to be due to so-called pioneer axons, which very quickly navigate the pathway to the
target tissue, ahead of most nerve fibers.
A review of relevant issues in nerve repair (18) arrived at several generalizations in the
approach to nerve repair. Despite prior evidence to the contrary, injured nerves should be
repaired as early as possible. There is no advantage to waiting until the metabolic
environment has been maximized. The current gold standard technique of repair remains
epineurial suture approximation of transected nerves with fine (9-0 or 10-0)
monofilament suture, with interposition grafting using an autologous nerve if a
tensionless repair cannot be achieved. What comprises tensionless continues to be
debated; however, if the resected nerve segment is greater than 2 cm, most investigators
would advocate grafting.
The most immediate promising innovations in neural regeneration include the use of
tubulization techniques combined with trophic substances such as neurocytokines,
including nerve growth factor, BDNF, ciliary neurotrophic factor, and neurotrophins-3, -
4/5, and -6. The complex interactions between these proteins and their target cells are still
being elucidated (Fig. 16.7). Although the enhancement in recovery using neurotrophic
substances has only been achieved in animal models, in some instances the differences
are impressive. In a rodent sciatic nerve model, Utley et al. (10) reported statistically
significant improvements in functional nerve recovery with the use of collagen
tubulization or the delivery of BDNF to the nerve bed. The best recovery was achieved in
those animals that received the BDNF by cross-linking it to the tubule itself (Fig. 16.8).
This enhancement has been confirmed in subsequent studies (11), and its effect is
apparent even when nerve repair is delayed (19). There is great expectation that the future
will bring even more precise pharmacologic options for the enhancement of nerve
regeneration. For the present, careful microsurgical suture reapproximation remains the
best way to facilitate the normal nerve healing process.

FIGURE 16.7. The complex interactions between
neurotrophic factors and their target cells continue to be
elucidated; a summary of the current understanding is
indicated. FGF, fibroblast growth factor; CNTF, ciliary
neurotrophic factor; BDNF, brain-derived neurotrophic
factor. (From Nishi R. Two neurotrophic factors are
better than one. Science 1994;265:10521053, with
permission.)



FIGURE 16.8. Comparison of the functional recovery
after sciatic nerve transection and repair in a rat model.
Nerves repaired by collagen tubulization (CT) with brain-
derived neurotrophic factor (BDNF) covalently cross-
linked to the collagen matrix (CT/linked-BDNF)
demonstrated the most rapid and complete regeneration
of all groups. EC, epineurial coaptation; CT/pumped-
BDNF, CT with BDNF delivered by an osmotic pump to
the repair. (From Utley, et al. Brain-derived neurotrophic factor and collagen tubulization
enhance functional recovery after peripheral nerve transection and repair. Arch
Otolaryngol Head Neck Surg 1996;122:407413, with permission.)



Bone Healing
Bone shares with the liver the distinction of being the only organs capable of spontaneous
regeneration with restoration of lost structure (20). Because of this property, bone has the
capacity to heal through regeneration, rather than scar formation, when certain conditions
are present. These conditions include accurate anatomic reduction, lack of mobility, and
adequate vascular supply. The potential for this type of healing is provided by rigid
fixation with plates and screws but must be weighed against the increased incidence of
infection (21). A significant innovation in the field of bone plating has been the
refinement of absorbable plates, which are enjoying widespread use for facial fracture
repair (22).
Under most circumstances, fractured bones undergo secondary healing. This process is
similar to the wound healing described at the beginning of this chapter but includes the
intermediate stages of soft (cartilagenous) callus and hard (bony) callus formation. These
calluses serve to stabilize the fracture, allowing the influx of osteoclasts and osteoblasts
that work in concert to calcify the callus (20). These activities are modulated by bone
morphogenetic proteins, cytokines that have the ability to induce differentiation of
mesenchymal cells into osteoblasts, and proliferation of cells involved in bone healing.
Mucosal Wound Healing
Most comparisons of the healing of wounds created by various surgical instruments
(knife, electrocautery, laser) have been carried out on skin in porcine models. The
popularity of laser-assisted oral cavity and oropharyngeal procedures, including laser-
assisted uvulopalatoplasty, has led authors to investigate the healing of mucosal wounds
(23). There appears to be no disadvantage in wound healing when comparing laser to
more conventional techniques, allowing the practitioner to make a choice of instruments
based on cost, availability, ease of use, and hemostasis instead of healing properties.
When poor mucosal healing after major head and neck surgery results in a wound
dehiscence, a mucocutaneous fistula may result. Although the causes of fistulae are
debated (including technical factors, localized infection, prior irradiation, and poor
nutrition), it is widely accepted that continued presence of infection and salivary spillage
may combine to delay closure. The use of systemic antibiotics is usually advocated.
There is anecdotal evidence of improvement in healing when antisialogogues (like
glycopyrrolate) are used to diminish the salivary flow, but a mechanical alternative such
as a salivary bypass tube or gauze packing may provide the same benefit.
Healing of Skin Grafts
The three sequential phases of skin graft survival include imbibition, a Latin derivative
meaning to drink, in which the graft absorbs its nutrients from the underlying recipient
bed; inosculation, from the Latin to kiss, in which the blood vessels present in the skin
graft grow to meet the preexisting blood vessels of the recipient bed and together form a
series of arborizing blood vessels; and neovascularization, in which new blood vessels
form, bridging the graft to the underlying tissues. These stages may be adversely affected
by numerous conditions, including the presence of systemic diseases, or local factors
such as mobility of the graft, infection, or fluid collection beneath the graft.
A significant advance in the field of skin grafting has come through tissue engineering, in
the form of epidermal and dermal skin substitutes. The epidermal grafts currently use
cultured autologous or allogeneic epidermal cells. The autologous grafts require 2 to 3
weeks to grow a sufficient number of cells, so allogeneic grafts are more commonly used.
Dermal grafts have found more applications in the field of otolaryngology. The cadaveric
allograft skin is chemically treated to remove the antigenic epidermal cellular
components, leaving an acellular dermal matrix and intact basement membrane complex
that is suitable for intraoral resurfacing (24), septal perforation repair, and soft tissue
augmentation.
Keloids and Hypertrophic Scars
A keloid is defined as the production of an overgrowth of dense fibrous scar tissue that
extends beyond the borders of the original skin injury. Hypertrophic scars, by contrast,
may be associated with the deposition of excessive scar tissue, but this scar tissue
remains within the confines of the original cutaneous injury. Unlike hypertrophic scars,
which may undergo some degree of wound contraction, keloids do not flatten or regress,
and they may occur spontaneously. Promising work at the molecular level has already
demonstrated elevated levels of TGF-1 and TGF-2 in the fibroblasts from keloids,
compared with fibroblasts from normal tissues. Continued molecular investigation is
likely to yield a greater understanding of the cause of keloids and hypertrophic scars and
may lead to potential mechanisms for treatment.
Several techniques have been proposed to treat keloids, and their number reflects the
disappointing results of any given approach. These include intralesional steroids,
cryotherapy, radiation therapy, laser therapy, elastic compression garments, and silicone
gel sheeting. Retrospective studies have suggested a role for either radiation therapy or
triamcinolone after surgery, but convincing data supporting these modalities have only
recently been reported. Sclafani et al. (25) completed a prospective randomized
investigation comparing steroid injections and radiation therapy for the treatment of
keloids. Although there was no control group or blinding, their study allowed the most
confident comparison between radiation and triamcinolone; radiation therapy was proved
to be superior. This conclusion must be tempered against the costs and risks of radiation
therapy, including injury to normal tissues and induction of neoplasia.
Innovative techniques for the treatment of keloids are being explored, including the use
of cultured keratinocyte grafts, although these remain experimental models. Other
therapies that have been tried include surgery combined with radiation or steroids and
interferon-2b, which, when combined with surgery, offers a mere 8% recurrence rate.
Such combination therapies appear to provide the best chances for preventing recurrences
of keloids.
FUTURE OF WOUND HEALING
This chapter reflects many of the exciting changes that have occurred in the field of
wound healing since the last edition. No doubt, the twenty-first century will bring an
increasing understanding of the molecular mechanisms of wound healing, which will
provide as yet unimagined potential for modulation of normal and abnormal wound
healing.
Research regarding the role of cytokines in wound healing has advanced sufficiently to
make pharmacologic manipulation of wounds a reality. The next phase in this discipline
will be the economic production of ample quantities of these cytokines, so that everyday
use may be feasible. An alternative method of delivery may involve the use of gene
therapy.
Finally, as the digestion and dissemination of scientific data becomes more efficient and
effective in this information age, the practicing surgeon will be better informed and
continue to progress beyond the days of laudable pus as an objective for healing
wounds.

HIGHLIGHTS
The three basic types of wound repair after injury are primary
healing, delayed primary healing, and secondary or spontaneous
wound healing.
Wound healing occurs as a result of dynamic and complex
interactions. Four overlapping phases can be identified,
including coagulation phase, inflammatory phase, fibroplasia
phase, and remodeling phase.
Even under ideal circumstances, cutaneous scars will be no
stronger than 80% of the strength of normal skin.
After wounding, scar maturation develops as an equilibrium is
achieved between collagen production and collagen lysis.
Many of the wound-healing processes are modulated by
cytokines (growth factors); the most important are TGFs, EGF,
PDGF, FGFs, and GH.
Numerous conditions may deter the normal wound-healing
process, including radiation, steroid administration, poor
nutrition, advanced age, and tissue hypoxia (from diabetes
mellitus or tobacco use, among others).
Fetal wound healing occurs in a scarless fashion; this unique
property may be able to be exploited in the future.
Nerve regeneration in humans occurs at a rate of approximately
1 mm/day, but this number may vary considerably.
Bone healing may occur as spontaneous regeneration of tissue
rather than the usual process of scar (callus) formation. This
requires anatomic reduction, absolute immobility, and adequate
vascularity.
The survival of split-thickness skin grafts depends on a three-
part process of imbibition (diffusion of nutrients from the
underlying bed), inosculation (anastomosis of graft blood
vessels with recipient bed blood vessels), and
neovascularization (new blood vessel formation).
CHAPTER REFERENCES
1. Cotran RS, Kumar V, Collins T, et al., eds. Robbin's pathologic basis of disease. Philadelphia:
W.B. Saunders, 1999.
2. Adams SL. Regulation of collagen gene expression. In: Zern MA, Reid LM, eds. Extracellular
matrix. New York: Marcel Dekker, 1993.
3. Roberts AB, Sporn MB. Physiological actions and clinical applications of transforming growth
factor-beta (TGF-beta). Growth Factors 1993;8:19.
4. Nall AV, Brownlee RE, Colvin CP, et al. Transforming growth factor beta 1 improves wound
healing and random flap survival in normal and irradiated rats. Arch Otolaryngol Head Neck Surg
1996;122:171177.
5. Herndon DN, Nguyen TT, Gilpin DA. Growth factors: local and systemic. Arch Surg
1993;128:12271233.
6. Brown GL, Nanney LB, Griffen J, et al. Enhancement of wound healing by topical treatment with
epidermal growth factor. N Engl J Med 1989;321:7679.
7. Rees RS, Robson MC, Smiell JM, et al. Becaplermin gel in the treatment of pressure ulcers: a
phase II randomized, double-blind, placebo-controlled study. Wound Repair Regen 1999;7:141
147.
8. Robson MC, Hill DP, Smith PD, et al. Sequential cytokine therapy for pressure ulcers: clinical and
mechanistic response. Ann Surg 2000;231:600611.
9. Ramirez RJ, Wolf SE, Barrow RE, et al. Growth hormone treatment in pediatric burns: a safe
therapeutic approach. Ann Surg 1998;228:439448.
10. Utley DS, Lewin SL, Cheng ET, et al. Brain-derived neurotrophic factor and collagen tubulization
enhance functional recovery after peripheral nerve transection and repair. Arch Otolaryngol Head
Neck Surg 1996;122:407413.
11. Ho PR, Coan GM, Cheng ET, et al. Repair with collagen tubules linked with brain-derived
neurotrophic factor and ciliary neurotrophic factor in a rat sciatic nerve injury model. Arch
Otolaryngol Head Neck Surg 1998;124:761766.
12. Yao M, Terris DJ. Surgical management of radiation-injured tissues of the head and neck. Front
Radiat Ther Oncol 1999;37:4962.
13. Sassler AM, Esclamado RM, Wolf GT. Surgery after organ preservation therapy. Analysis of
wound complications. Arch Otolaryngol Head Neck Surg 1995;121:162165.
14. Atkinson JB, Kosi M, Srikanth MS, et al. Growth hormone reverses impaired wound healing in
protein-malnourished rats treated with corticosteroids. J Pediatr Surg 1992;27:10261028.
15. Toriumi DM, O'Grady K, Desai D, et al. Use of octyl-2-cyanoacrylate for skin closure in facial
plastic surgery. Plast Reconstr Surg 1998;102:22092219.
16. Sullivan KM, Lorenz HP, Meuli M, et al. A model of scarless humanfetal wound repair is
deficient in transforming growth factor beta. J Pediatr Surg 1995;30:198202.
17. Sunderland S. Nerves and nerve injuries. New York: Churchill Livingstone, 1978.
18. Terris DJ, Fee WE Jr. Current issues in nerve repair. Arch Otolaryngol Head Neck Surg
1993;119:725731.
19. Moir MS, Wang MZ, To M, et al. Delayed repair of transected nerves: effect of brain-derived
neurotrophic factor. Arch Otolaryngol Head Neck Surg 2000;126:501505.
20. Feinberg SE, Larsen PE. Healing of traumatic injuries. In: Fonseca RJ, Walker RV, eds. Oral and
maxillofacial trauma. Philadelphia: W.B. Saunders, 1991:1357.
21. Terris DJ, Lalakea ML, Tuffo KM, et al. Mandible fracture repair: specific indications for newer
techniques. Otolaryngol Head Neck Surg 1994;111:751757.
22. Pensler JM. Role of resorbable plates and screws in craniofacial surgery. J Craniofac Surg
1997;8:129134.
23. Liboon J, Funkhouser W, Terris DJ. A comparison of mucosal incisions made by scalpel, CO
2

laser, electrocautery, and constant-voltage electrocautery. Otolaryngol Head Neck Surg
1997;116:379385.
24. Rhee PH, Friedman CD, Ridge JA, et al. The use of processed allograft dermal matrix for intraoral
resurfacing: an alternative to split-thickness skin grafts. Arch Otolaryngol Head Neck Surg
1998;124:12011204.
25. Sclafani AP, Gordon L, Chadha M, et al. Prevention of earlobe keloid recurrence with
postoperative corticosteroid injections versus radiation therapy: a randomized, prospective study
and review of the literature. Dermatol Surg 1996;22:569574.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

17 OUTPATIENT EVALUATION AND DIAGNOSIS
Head & Neck SurgeryOtolaryngology
17




OUTPATIENT EVALUATION AND DIAGNOSIS
JAMES A. DUNCAVAGE
JOHN R. COLEMAN, JR.

J.A. Duncavage: Department of Otolaryngology, Vanderbilt University Medical Center, Nashville,
Tennessee.
J.R. Coleman, Jr.: Atlanta Center for ENT and Facial Plastic Surgery, Atlanta, Georgia.


Room and Equipment
Patient History
Physical Examination
Ears
Nose
Oral Cavity
Oropharynx
Nasopharynx
Hypopharynx
Larynx
Neck
Face
General and Neurologic Examination
Laboratory Tests
Imaging
Telemedicine
Laser in the Clinic
Video in the Office
Clinic Office Operative Procedures
Consent
Occupational Transmission of Disease
Universal Precautions in the Clinic
Sterilization of Equipment
Chapter References
ROOM AND EQUIPMENT
Otolaryngologists are concerned with the diagnosis and treatment of patient illness.
Ideally, the space in which we evaluate patients should be easily accessible, should offer
a pleasant comforting environment, and should be equipped with modern instruments.
The patient space should be visualized as an area that must serve three groups: the
patient, the physician, and the office personnel. The patient needs a comfortable waiting
room and a convenient check-in area. More importantly, the examining room should be
large enough to allow placement of equipment and accommodate the patient's family. A
room size of 10 to 12 feet has been adequate to meet these requirements in our practice.
A storage area and sink are placed in an accessible part of the room. Radiologic view
boxes (ideally at least two) are placed side by side in the room, allowing both the patient
and the physician to see the radiographs.
Two comfortable chairs adjacent to the interviewer's desk are provided for the patient and
a family member. This arrangement helps to establish eye contact and allows the
physician to establish a rapport with the patient before the examination begins. The
selection of an examining chair should be based on the cost and the comfort it provides.
The chair should have an easily adjustable head rest and an accessible height adjustment,
preferably hydraulic, so that the patient can be moved to a height that is comfortable for
the examiner. It should be possible for the back of the chair to be removed quickly in the
event of a patient vasovagal reaction. The chair base should be stable so that the chair
back can be dropped without unbalancing the chair, and adequate distance should be
maintained from the wall to allow this maneuver.
A table with drawers and an adequate space on top for storage of routine examining
equipment is important. Certain topical medicines also can be stored here. The commonly
used unit has a pull-out shelf for additional space, but we have found this shelf to be of
little help because it makes the drawers inaccessible.
A large amount of equipment is used for the examination in an otolaryngology office.
There should be adequate provision for the proper maintenance and storage of all
equipment. The ear speculums, nasal speculums, tongue blades, mirrors, and gloves are
conveniently placed on the examination table beside the examination chair.
The use of endoscopes in the office allows a more complete examination. These are
costly pieces of equipment and should be handled with care. Recommended cleaning
procedures must be followed both for patient safety and for protection of the instruments
(see Sterilization of Equipment, below).
We routinely use a flexible nasopharyngoscope. This instrument is invaluable because of
its ability to examine the nasopharynx, hypopharynx, larynx, and proximal trachea. The
nasopharyngoscope is covered and stored on a cart with other endoscopes between the
examining rooms when not in use. A small Storz light box with an adapter is kept on the
examination table (Fig. 17.1). A bright light with a xenon source is necessary for photo
documentation when using the flexible nasopharyngoscope (Fig. 17.2).

FIGURE 17.1. Storz light box used in flexible
nasopharyngoscopy.



FIGURE 17.2. Xenon light source needed for
photodocumentation when flexible nasopharyngoscope is
used.



The rigid endonasal telescopes have become invaluable examination instruments. We
prefer the small-diameter 25- to 30-degree telescopes for the office. The same light box is
used for rigid and flexible nasopharyngoscopes. A rigid laryngoscope (70 to 90 degrees)
is needed for video documentation of the larynx.
A full setup for laryngeal examination is costly, but this equipment is not necessary for
all offices. This chapter presents the setup used by our department's speech pathologists.
A monitor-quality television is used with a high-quality super VHS and a 0.75-inch video
player. A xenon light source is incorporated. A chip video camera of high resolution and
a low lux is used to record each examination.
A stroboscopic unit is also available for careful examination of vocal fold motion (Fig.
17.3). A video printer, which allows immediate photo documentation, is an integral part
of this system (Fig. 17.4). It is easy to make 35-mm slides from the video print.

FIGURE 17.3. Stroboscopic unit used to examine vocal
fold motion.



FIGURE 17.4. Video printer provides immediate
photodocumentation.



It is difficult to do videostroboscopy with the flexible scope because of the light lost by
the scope and camera. We currently use a rigid laryngoscope for videostroboscopy in all
our patients as tolerated.
PATIENT HISTORY
Obtaining a patient history is an art. If the correct questions are asked, the patient will tell
the physician what is wrong. A nurse can record the patient's chief complaint and review
of systems before the physician enters the room. This interaction with the nurse allows
the patient time to think more about why he or she has come to see the doctor. Care must
be taken to record all medication allergies and all medications used by the patient,
including nonprescription medications.
When entering the room, physicians should introduce themselves to the patient, try to
gain the patient's confidence, and make the patient feel at ease. We find it helpful to make
a quick search for a common ground by allowing patients to discuss their interests or
hobbies. This takes only 1 to 2 minutes, but it allows patients an opportunity to talk about
something they are comfortable with, and a sense of camaraderie can be established. It
also reminds the physician to be a good listener.
Once the patient is at ease, the history taking can start. We find it helpful to ask patients
in straightforward terms to explain what is bothering them and to let patients explain their
problems in their own words. In the case of conflicting chief complaints, we ask which
problem is the most important. Although the physician must make the patient feel
comfortable, the questioning must direct the process in an efficient manner. The
questioning should be clear, concise, and done in a steady manner. If the discussion gets
sidetracked, the physician must bring it back on course.
PHYSICAL EXAMINATION
The physical examination is the second most important part of the outpatient evaluation.
The patient seems to dread this part most. In reality, an otolaryngologic examination does
not need to be uncomfortable for the patient.
The examiner should have all the equipment within reach. Before starting, the physician
should explain to the patient in general terms what is going to happen. Seeing a thorough
cleansing of the examiner's hands helps the patient feel more comfortable about being
touched. We prefer to talk with the patient during the examination, explaining in general
terms what we are finding.
The American Academy of Otolaryngology-Head and Neck Surgery recently introduced
a 10-point comprehensive otolaryngologic examination. Although each examiner will
have a different style and order, each aspect should be included in a detailed examination.
We discuss our approach to each aspect of the examination.
Ears
The auricle should be inspected. A gentle movement of the external ear should be done to
determine whether there is any pain. The speculum is inserted gently into the canal. The
examination should include the tympanic membrane, its mobility, the middle-ear space as
visualized through the membrane, and the ear canal. We examine the ear canal when
removing the speculum. Cerumen obstructing examination of the tympanic membrane
should be removed gently. Both ears should always be examined. Tuning forks and
audiologic evaluation contribute greatly to this examination.
Nose
The external symmetry and appearance of the nose should be noted. The nasal tip should
be elevated gently and the anterior nares examined for the condition of the caudal
septum. The nasal speculum should be inserted gently with a finger providing stability on
the nasal dorsum. The color and degree of swelling of the inferior turbinates, the contour
of the septum, and the presence of crust or purulent debris all should be noted. If the
history indicates a possibility of nasal pathology, a more detailed examination of the nose
is necessary.
The nasal mucosa can be decongested and anesthetized with a combination spray. We
prefer Neo-Synephrine with tetracaine. After the decongestant and anesthetic have
produced their effects, the examination of the nose can begin. We prefer the rigid
endoscopes if only a close nasal examination is necessary. If we plan to examine the
nasopharynx or larynx in a patient who cannot be visualized with the mirror, we use the
flexible nasopharyngoscope for the nasal, nasopharyngeal, and laryngeal examinations.
The small-diameter 25- to 30-degree scope is passed into the nose parallel to the floor. In
looking through the scope as it is passed into the nose, you must be aware that you are
looking 25 to 30 degrees off to the side. This angled view can adversely affect the
passage of the telescope, producing discomfort to the patient. The angled lens should be
directed to the lateral nasal wall. After the middle meatus is viewed, the scope is
advanced to view the superior meatus and nasal roof. It is not always possible to see the
superior meatus or the sphenoid ethmoidal recess. Nasal septal abnormalities can limit
the use of the rigid nasal telescopes.
Oral Cavity
The oral cavity requires good lighting for careful inspection, and the lighting should be
parallel to the viewer's visual axis. Two wooden tongue blades, one in each hand, are
used to move the lips and tongue to visualize all mucosal surfaces adequately. A
palpation of the tongue and an assessment of its mobility should be done. The hard palate
and premaxilla are commonly overlooked because of the difficulty in viewing this area,
but using a mirror or having the patient extend his or her neck will provide a good view.
Oropharynx
The oropharynx is visualized using the parallel light source, tongue blades, and a no. 5
dental mirror. During the examination, the symmetry of paired structures should be
noted. The character and contour of the base of tongue should be described. A gloved
finger should palpate the base of tongue.
Nasopharynx
The nasopharynx is easy to visualize in some patients. If during the oral cavity
examination the patient does not appear to have a strong gag reflex, we use a 00-0 dental
mirror to visualize the nasopharynx. In most cases, a flexible nasopharyngoscope is
passed through the nose after a topical decongestant with an anesthetic has been applied.
The physician should comment on the appearance of the mucosa, adenoid pad, and
eustachian tube orifices.
Hypopharynx
The hypopharynx can be visualized best by using a no. 5 dental mirror. The indirect
examination allows a close view of the vallecula and lingual surface of the epiglottis. The
lateral walls also are easily seen. When the flexible nasopharyngoscope is used, it may be
difficult to see the vallecula. We prefer the mirror examination if the patient can tolerate
it.
Larynx
The larynx is a fascinating organ to examine. It challenges our technical and diagnostic
expertise. We prefer a mirror for the basic examination. The patient is at the same height
as the examiner. The patient then leans forward and in the sniffing position occludes
both nares using the left hand. We grasp the tongue and position the mirror in the
oropharynx so that the reflected light illuminates the larynx. We first examine the color
of the mucosa, we then assess the epithelium, and finally we examine the true vocal fold
mobility. The mirror examination offers an excellent opportunity to judge whether
inflammation is present. The reflected light does not wash away color. The indirect
laryngeal examination does not visualize the anterior larynx well. We have found it
difficult in many patients who have a change in vocal fold mobility to judge movement
on the indirect examination adequately.
The flexible nasopharyngoscope provides a comfortable way to examine most patients,
but it does not provide good color contrast. When coupled to a video camera and
recorder, an excellent assessment of vocal fold mobility can be made.
Other excellent options for assessing the larynx are the rigid 90- and 70-degree
laryngoscopes. These scopes have excellent optics and provide a superior picture when
used with a video camera. These are the scopes of choice of our speech pathologists.
Neck
Examination of the neck should start with a good look for asymmetry. The patient should
be at the same height as the examiner. The right-handed examiner should stand on the
patient's right side. The neck should be steadied by one hand when palpating with the
other. An organized approach should be used to palpate all the triangles, including the
supraclavicular area and the submental area. A record should be kept describing the
location, site, shape, tenderness, mobility, and temperature of all masses.
The thyroid examination requires the patient to sit forward. The patient should be
informed that two hands will be placed around his or her neck. The midline neck
structures should be identified. The thyroid gland then can be found and palpated.
Face
A look at the patient's face should judge symmetry and motion. The eyelids and eyes
should be viewed with attention to any ptosis, proptosis, and pupillary asymmetry.
The skin of the face and scalp should be inspected. If no patient complaints are voiced
about the skin, a brief look is all that is necessary.
General and Neurologic Examination
Cranial nerves I through XII should be examined. Depending on the patient's history or
physical examination findings, additional neurologic examination may be appropriate.
Finally, the physician should note overall patient characteristics, including nutritional
status and cognitive function.
LABORATORY TESTS
The increasing cost of health care may someday change how otolaryngologists practice
their specialty. Physicians should be knowledgeable about the cost of a test and should do
a quick cost-benefit analysis before ordering the test. The decision to order a particular
test should be based on the patient's history and physical examination. The test should
provide useful information that will lead to a diagnosis. Although much has been said
about defensive medicine and ordering tests for legal prophylaxis, a test that is 100%
sensitive has not yet been developed. If the examiner believes the history and the
examination leaves little doubt about the diagnosis and the diagnosis is benign, the
physician should discuss with the patient confirming the diagnosis with a noninvasive
test. This discussion should include the positive and negative aspects of the test. If the
patient elects to postpone the test, the physician should document this in the chart and
recommend close follow-up.
Recording test results is cumbersome and defies an easy solution. We find it helpful to
instruct the patient to call for the laboratory results and document that the patient is to call
for the results. After the patient calls, a note is placed in the chart documenting the results
and indicating that they were discussed with the patient. If the patient does not call, it is
often difficult to identify that there was no follow-up on the test results.
IMAGING
The advances in tissue imaging during the last 10 years have been extraordinary. The
remarkable ability of computed tomograms to show what is under the skin has been
surpassed by magnetic resonance imaging to show us a clear image of the subcutaneous
structures. (Information about imaging concepts and diagnostic techniques is presented in
Chapter 6.) The diagnosis and treatment of otolaryngologic diseases will continue to
improve with advancements in technology.
TELEMEDICINE
A new development since 1959, telemedicine seeks to provide consultant and diagnostic
assistance to health care providers at distant sites, to have a direct impact on patient care
at distant sites, and to provide educational services for health care providers.
Telemedicine is a rapidly growing vehicle that assists in providing specialized care to
underserved areas. With the recent advances in endoscopic equipment, video storage, and
transfer vehicles, the practice of otolaryngology now has been performed via
telemedicine.
Teleotolaryngology has become a reality as reported by Blakeslee et al. (1), who reported
success in using three different telemedicine systems in an otolaryngology practice.
Recent improvements in the technology and telecommunications provide the high-quality
audio and visual communication that are needed for satisfactory clinical diagnosis. One
report from the U.S. Military Healthcare System concluded that 31,000 conventional
consultations in Europe could be replaced by telemedicine, yielding potential savings of
$3.7 million and 25,000 working days (2). Burgess et al. (3) described how a stepwise
program of telemedicine and telelearning can be introduced into a residency program or a
private practice in a manner that will allow us to exploit this new technology more
effectively.
As technology continues to improve, we will no doubt see increasing use of telemedicine
to provide specialty care in underserved areas. Numerous questions regarding
availability, malpractice, and licensure will need to be addressed, but this growing area
surely will have a profound impact on the future practice of clinical otolaryngology.
LASER IN THE CLINIC
The use of lasers in the clinic has many advantages. In addition to the reduction in cost
and the convenience to both the patient and the surgeon, the laser can facilitate growth of
the physician's practice into new and varied areas. Although laser physics and the
advantages and disadvantages of each type of laser are beyond the scope of this chapter,
we give a few basics on deciding whether to buy a laser (4). In the end it all comes down
to economics: Does the income generated by the laser justify the cost of the equipment,
the training of personnel, and the dedication of space? The first point to consider is the
type of practice and the additions to that practice the laser could bring. Lasers can be used
for a variety of cosmetic, oral cavity, nasal, and myringotomy procedures. More
specifically, would current patients benefit from a laser procedure over a conventional
procedure? The second issue is the training of personnel to service the laser. The safety
guidelines that should be followed are quite extensive, and dedicated personnel make the
use of the laser safer and more efficient. A complete description of the necessary safety
requirements can be found in the American National Standards Institute guidelines for the
safe use of lasers. Finally, is space available for the laser? The laser must occupy a room
that can be partitioned off from the office so that strict eye protection can be enforced.
VIDEO IN THE OFFICE
The ability to video or video print a patient's examination in the office may become the
standard of care in the near future. We have already witnessed this change in laryngology
with videostroboscopy.
The use of video prints has two advantages. One is educational. A patient can be taught
more by being shown a picture of herself or himself during the explanation and can refer
back to the picture after leaving the office and have a visual reminder of the conversation.
Moreover, if the patient is provided a written explanation of his or her condition, the
picture can be used to review the written material. The second reason for the video print
is documentation. The video print can be used on subsequent visits for comparison after
treatment, and the print serves as a permanent record of the original problem. Video
information can be stored on a computer disk for future use, which facilitates record
keeping and limits storage space.
CLINIC OFFICE OPERATIVE PROCEDURES
The ability to perform procedures in the office setting is beneficial to both the patient and
the otolaryngologist. To the patient, the thought of going to the operating room can be an
anxiety-provoking expensive experience. Each patient that we recommend for a surgical
procedure should be evaluated to determine whether the procedure could be done in the
clinic. For instance, we have found that many sinus procedures can be done in the office.
Examples include partial middle turbinectomy, nasal antrostomy, partial ethmoidectomy,
scar release for the sphenoid, maxillary and frontal sinus ostia, polypectomy, and
maxillary endoscopy. Doing procedures in the office actually saves the surgeon time,
because it eliminates much of the waiting in the operating room. In addition, surgeons
can save their operating room time for more challenging surgical procedures. The
College of Surgeons has established guidelines for optimal office-based surgery (5).
CONSENT
The issue of informed consent for a surgical procedure in the operating room begins in
the office. The Professional Liability Committee of the College of Surgeons states that
consent is a continuing education process that results in a joint decision to pursue a
specific treatment plan (6). The otolaryngologist must include the patient in all decisions,
which is accomplished through patient education in the office. The use of pictures,
anatomic models, and prepared video of the patient's problem all can be used to educate
the patient so that an informed decision can be made by the patient for treatment.
The signing of the consent is usually done at the hospital or day-surgery center the day of
the surgery. This setting is not the ideal, however, because the patient is under duress and
the surgeon may not have ample time to explain the planned treatment, its risks, benefits,
and alternatives. For these reasons, the office is the best setting to discuss consent. We
developed an office consent form that covers the main points of an informed consent.
The office consent form lists the planned surgical procedure and provides an explanation
of the procedure, including why surgery is recommended. Next, the office consent covers
the risks, both common and serious, of the planned procedure. The issue of patient
discomfort as a result of the surgery is discussed. The patient then signs the form,
acknowledging having had an opportunity to ask questions about the proposed treatment.
The patient also indicates that he or she wants to have the surgical procedure performed
and checks the box next to the explanation that a change of mind is possible anytime. The
patient and the doctor then sign the form and date it.
Planning a patient's treatment, including a surgical procedure, is not to be taken lightly by
the surgeon. For a patient, any trip to the operating room is an experience that brings out
fear of the unknown. All the facts about the procedure must be explained, and the patient
must be given every opportunity to ask questions and to understand any alternatives to
surgery. We highly recommend the College of Surgeons liability/risk management
manual for further reading on this topic (6).
OCCUPATIONAL TRANSMISSION OF DISEASE
In the otolaryngology clinic, the risk of transmission of disease exists both from the
physician to the patient and from the patient to the physician. Close contact with patients,
the numerous body fluids physicians encounter, and the increasing need for
outpatient/clinic-based invasive procedures have increased the risk of disease
transmission to the physician and to patient. Furthermore, it is estimated that up to 70%
of human immunodeficiency virus (HIV)-infected persons will consult an
otolaryngologist for head and neck symptoms; often this encounter occurs before the
diagnosis of acquired immunodeficiency syndrome has been made (7). Moreover, the
HIV virus has been cultured from tears, middle ear effusions, and saliva; antibodies to the
virus have been isolated in cerumen, tears, middle ear effusions, and saliva.
Universal Precautions in the Clinic
In 1987 the Centers for Disease Control and Prevention brought forth recommendations
regarding the handling of blood products. These guidelines are referred to as universal
precautions. Since 1992 they have also been applied to the otolaryngology clinic under
the supervision of the Occupational Safety and Health Administration. These guidelines
require appropriate protective barrier precautions and handling and disposal of infective
materials.
Despite widespread knowledge of these precautions, health care workers do not always
follow these recommendations closely. One recent study reported that 46 residents and 4
medical students were observed as they performed 128 invasive procedures in a tertiary
care children's hospital. Universal precaution guidelines were followed correctly only
54% of the time (8). Several similar studies have reached the same conclusion,
underscoring the need for more effective educational programs.
We must make deliberate attempts to improve the use of universal precautions not only
because of the fear of sanctions but also to protect ourselves and our patients. Each office
must have an exposure control plan that outlines and documents health care workers'
training in and knowledge of universal precautions and prevention of disease transfer.
Each otolaryngologist should wear gloves for all examinations in which contact with a
body fluid will occur. Protective eyewear should be worn for all invasive procedures and
other instances when splashes and sprays of infective materials may be encountered (i.e.,
endoscopy). The physician should consider wearing a face mask during all endoscopies.
Finally, all patients should be treated equally in terms of protective measures taken.
Sterilization of Equipment
Another facet in the prevention of occupational transmission of disease is sterilization of
the work environment and instruments used. Numerous articles have been published that
discuss the merits of different disinfectants in the elimination of bacterial and viral
vectors. Other articles have examined the potential for cross-contamination of reusable
equipment. One article of particular interest examined the risk of cross-infection with a
multiuse nasal atomizer (9). These authors were able to document the contamination of
the atomizer tip, nozzle, and reservoir with bacteria isolated from the nasal vestibule.
Other groups examining dental and gastrointestinal endoscope sterilization found
removal of lubricants and organic debris before the process to be the central facet in
ensuring effective sterilization.
Recommendations for the office, therefore, include effective cleaning of all equipment
and surfaces to remove particulate matter after each patient care contact. Disinfection of
all surfaces with an antibacterial/antiviral agent should be performed. Instruments that
can be heat sterilized should be; those that cannot tolerate heat sterilization should be
immersed in antibacterial/antiviral solution for an appropriate period based on the
manufacturer's recommendation. Two percent glutaraldehyde has proved particularly
effective for the disactivation of the HIV virus. Finally, when possible, disposable
equipment should be used. An excellent example of this in our practice is the use of
disposable sheaths for our flexible nasopharyngoscopes.

HIGHLIGHTS
The ability to take a good history and to perform a thorough
head and neck examination are the mainstay of otolaryngology.
The establishment of good patient-physician rapport and the
sharing of information between the physician and the patient
remain important health care issues.
Patients must view physicians as compassionate,
knowledgeable, and well organized.
The use of diagnostic tests and recommendations for surgery
must be based on sound principles.
Physicians should know the cost of the tests they order and
decide whether the information that the test provides will have
an impact on the care of the patient.
Use of the office for minor operating procedures should be
considered whenever possible.
Consent is a dynamic process between the patient and the
surgeon and should be accomplished primarily in the office.
For patient and physician protection, universal precautions
should be followed during every clinical encounter.
CHAPTER REFERENCES
1. Blakeslee DB, Grist WJ, Stachura ME, et al. Practice of otolaryngology via telemedicine.
Laryngoscope 1998;108:1.
2. Navein J, Arose D, Pietermich A. A business model for telemedicine. J Telemed Telecare
1999;5[Suppl 1]:S76.
3. Burgess LPA, Holtel MR, Syms MJ, et al. Overview of telemedicine applications for
otolaryngology. Laryngoscope 1999;109:1433.
4. Ossoff RH, Coleman JA, Courey MS, et al. Clinical applications of lasers in otolaryngology/head
and neck surgery. Lasers Surg Med 1994;15:217.
5. Reiling RB, ed. Guidelines for optimal office based surgery, 2nd ed. Chicago: American College
of Surgeons, 1996.
6. Nora PF, ed. Consent and the process of informed consent. Professional liability/risk
management. Chicago: American College of Surgeons, 1991.
7. Kantu S, Lee DM, Lucente F. Safety awareness for the otolaryngologist caring for the HIV-
positive patient. Laryngoscope 1996;106:982.
8. Moore S, Goodwin H, Grossberg R, et al. Compliance with universal precautions among pediatric
residents. Arch Pediatr Adolesc Med 1998;152:554.
9. Spaggs PDR, Hanekom W, Mochloulis G, et al. The assessment of the risk of cross-infection with
a multi-use nasal atomizer. J Hosp Infect 1994;28:315.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

18 PERIOPERATIVE MANAGEMENT ISSUES
Head & Neck SurgeryOtolaryngology
18




PERIOPERATIVE MANAGEMENT ISSUES
DAVID M. BARRS

D.M. Barrs: Department of Otolaryngology, Duke University, Durham, North Carolina; Carolina Ear and
Hearing Clinic, Raleigh, North Carolina.


Preoperative Evaluation
Preoperative Malnutrition
Hematologic Management
Transfusions
Erythrocyte Abnormalities
Platelet Abnormalities
Disorders of Hemostasis
Intraoperative and Postoperative Bleeding
Thromboembolic Diseases
Preventive Measures
Diagnosis
Pulmonary Embolism
Management
Endocrine Abnormalities
Diabetes Mellitus
Thyroid and Parathyroid Disorders
Adrenal Glucocorticoids
Pituitary
Cardiovascular Disorders
Hypertension
Postoperative Hypotension
Arrhythmias
Pulmonary Disorders
General Management
Management of Postoperative Pulmonary Insufficiency
Gastrointestinal Disturbances
Stress Ulcers
Adynamic Ileus
Diarrhea
Renal Disease
Chronic Renal Failure
Acute Renal Failure
Neuropsychiatric Problems
Postoperative Seizures
Myasthenia Gravis
Cognitive Impairment
General Considerations
Postoperative Fever
Malignant Hyperthermia
Postoperative Pain
Surgery in the Chemically Dependent
Bibliography
This chapter presents selected aspects of medical management in the perioperative
period, which is defined as the time just before, during, and after the operative procedure.
PREOPERATIVE EVALUATION
History and physical examination remain the cornerstones of the preoperative evaluation.
In an era of cost containment, laboratory tests, radiographic examination, and
interspecialty consultation are performed on an outpatient basis and are tailored to finding
information that could modify or delay surgery. Patients with medical conditions need
more extensive examinations tailored to their problems. The incidence of abnormal
laboratory results is extremely low in the asymptomatic patient. Healthy pediatric patients
undergoing minor procedures such as pressure equalizing tube placement should need no
laboratory or radiographic evaluation. Pregnancy testing should be considered in sexually
active patients of childbearing age, because it is in the best interest of the mother and
fetus to consider a delay of elective surgery. Current American College of Surgeons
recommendations for preoperative testing are mentioned in the appropriate sections.
Preoperative Malnutrition
The daily caloric requirements for most adults are 25 to 35 kcal/kg of body weight.
Protein is usually required at 0.8 g/kg per day, but the critically ill patient may need an
increase to 1.2 to 2.0 g/kg per day. Most otolaryngology patients are well nourished, but
this is not the case with many head and neck cancer patients who have difficulty
maintaining an adequate oral intake to prevent weight loss. In the surgical patient, mild to
moderate malnutrition is defined as a recent weight loss of 6% to 12% of the usual body
weight (weight in the proceeding 3 to 6 months) with a serium albumin greater than 3.5
g/dL and serum transferrin concentration greater than 200 mg/dL. Severe malnutrition is
worse (i.e., weight loss greater than 12%, albumin less than 3.5 g/dL, serum transferrin
less than 200 mg/dL).
Patients with mild to moderate malnutrition may undergo most otolaryngology surgeries,
with attention given to nutrition in the postoperative period; however, severe malnutrition
should be treated with 7 to 10 days of nutritional replacement before elective surgery.
Because poor oral intake is presumed to have caused the malnutrition, most replacement
therapy should be in the form of intravenous (i.v.) nutritional therapy or nasoenteral tube
feedings. It is assumed that the gastrointestinal tract is intact and functional in most
otolaryngology patients. Nasogastric or nasojejunal tube feedings are preferred because
they are safer and more natural than total parenteral nutrition (TPN). Tube feedings can
be either a blenderized normal diet or a nutritionally complete commercial formula. The
commercial formulas normally are started as an isotonic solution given by continuous
gravity drip or by pump infusion at a rate of 30 mL/h. This rate is increased every 12 to
24 hours by 15-mL/h increments to a full dose in 2 to 4 days. In patients with long-term
nutritional needs, a gastrostomy tube, such as percutaneous endoscopic gastrostomy,
often is required.
For patients who are unable to take nutrition by the gastrointestinal tract, replacement
should be with TPN. The most common solution is a hypertonic solution containing 15%
to 20% dextrose, 4% to 5% crystalline amino acids, 10% fat emulsion, with electrolytes
and vitamins all within the same infusion bag. In general, the infusion is started with
1,000 mL in the first 24 hours and increased as tolerated to 2,000 mL/day. The safety of
TPN requires frequent monitoring. Vital signs, urine, glucose, acetone concentrations,
and fluid balance should be monitored several times daily. Body weight, electrolytes,
blood urea nitrogen, blood glucose and intake of fluid, protein, and calories are measured
daily. Weekly liver function studies, serum magnesium, total protein, albumin,
transferrin, and iron levels are measured. It is important in both enteral and TPN to
provide enough water to prevent azotemia and hypernatremia.
Tube feedings are withheld on the day of surgery. TPN is tapered before surgery but
continued on the day of surgery at one third to one half the usual rate. Both are resumed
in the postoperative period, especially if adequate oral intake is not expected for 5 to 7
days. For tube feedings, water may be provided within hours of the termination of
surgery, whereas full-strength formula at a rate of 30 mL/h can be started on the first
postoperative day for most patients.
HEMATOLOGIC MANAGEMENT
Transfusions
Rapid correction of hematologic deficiencies usually depends on blood transfusions.
Whole blood is rarely used; it is separated into its components for safety and efficiency
(Table 18.1). The broadest coverage for urgent coagulation abnormalities is fresh frozen
plasma, which contains all the clotting factors, although there are no platelets and the
fibrinogen level is low. For elective surgery, the patient can be an autologous donor with
a maximum of 1 U donated every 72 hours, up to 72 hours before surgery, as long as the
patient maintains a hematocrit of greater than 33%. Fibrinogen transfusion is no longer
used because of the high risk of viral transmission; cryoprecipitate is used to treat low
fibrinogen levels.

TABLE 18.1. BLOOD COMPONENTS



Mild hypersensitivity reactions are relatively common and can be controlled by
administration of antihistamines and temporary discontinuation of the transfusion. Febrile
reactions usually respond to simple discontinuation of the transfusion. Of specific
concern is the patient who has undergone massive transfusion. Volume overload may be
minimized by using packed red blood cells. Hyperkalemia, hypokalemia,
hyperammonemia, and acidosis do not require specific treatment other than monitoring of
blood levels. Platelets survive poorly in banked blood, and massive transfusions may lead
to significant thrombocytopenia. Hypothermia can be minimized by warming blood and
crystalline replacement. Citrate toxicity can cause a decrease in ionized calcium.
Replacement with either calcium gluconate or calcium chloride is reserved for
symptomatic hypocalcemia and is not given prophylactically. Clotting studies such as
prothrombin time (PT) and activated partial thromboplastin time (aPTT) should be
monitored for any sign of coagulopathy.
Erythrocyte Abnormalities
A preoperative hemoglobin should be obtained on all female patients but is not necessary
in asymptomatic male patients who do not have a history of bleeding or anemia. Anemia
is significant because of the decreased oxygen-carrying capacity available during
anesthesia. The previous minimal acceptable hemoglobin level of 10 g/dL for surgery or
transfusion has been lowered to 7 g/dL, which is adequate for tissue oxygen delivery if
circulating volume is normal. Healthy patients or chronically anemic patients may
undergo surgery safely at these levels if minimal blood loss is expected. In the urgent
case, transfusion may be necessary to replace erythrocytes to an acceptable hemoglobin
level.
Two hemoglobinopathies are of concern. The first is sickle cell disease. Sickle cell trait is
not associated with increased surgical risk. In patients with the homozygous condition,
the level of hemoglobin S should be reduced to about 50% by exchange transfusion to
avoid sickling crisis or acute chest syndrome during anesthesia or during the
postoperative period. Hypoxia, hypernatremia, and volume depletion should be avoided.
The second is glucose-6-phosphate dehydrogenase deficiency, which causes oxidant
damage to hemoglobin within erythrocytes and is almost exclusively seen in men.
Preoperative screening for this deficiency should be performed if there is a family history
of the deficiency or unexplained hemolysis. The condition is not a risk for surgery, but
certain medications should be avoided in the postoperative period to minimize the risk of
hemolysis.
Platelet Abnormalities
Thrombocytopenia is defined as a platelet count of less than 140,000/L. Counts less
than 50,000/L may be associated with bleeding problems during surgery. In the urgent
situation, platelet transfusions should be performed to raise the platelet count to over
50,000/L. Each unit of platelets will raise the platelet count 5,000 to 10,000/L, and the
platelet half-life is usually 2 to 3 days unless there is increased destruction. Ideally, the
platelet count should be maintained above 50,000/L for 3 to 4 days postoperatively.
Thrombocytopenia developing in the postoperative period is unusual unless massive
transfusion has been necessary, but sepsis, disseminated intravascular coagulation (DIC),
and drug-induced thrombocytopenia must be considered.
Qualitative platelet disorders with abnormalities in platelet function may exist even with
a normal platelet count. If a patient has a history of uremia, liver disease, or abnormal
bleeding from previous surgery or if there is a recent history of ingestion of aspirin,
nonsteroidal antiinflammatory drugs (NSAIDs), or other medicine that may affect platelet
function, a bleeding-time test should be performed. Bleeding times longer than 10
minutes are considered abnormal, and the urgency of surgery must be considered. With
minor elevations and in surgical sites where bleeding is easily controlled, surgery may
proceed if platelets are available. If the bleeding time is longer than 20 minutes, elective
surgery should be canceled. Platelet transfusions or administration of desmopressin
acetate should be performed if emergency surgery is necessary.
Disorders of Hemostasis
The yield of routine PT and platelet counts is quite low unless the patient's history
indicates a bleeding problem. This history should be searched carefully for congenital or
acquired abnormalities of bleeding (Table 18.2).

TABLE 18.2. DISORDERS OF HEMOSTASIS



The perioperative management of patients on anticoagulant therapy requires specific
information. Heparin blocks the intrinsic hemostatic pathway by potentiating the activity
of antithrombin III, and warfarin is a vitamin K antagonist and decreases production of
vitamin K-dependent clotting factors. The need for anticoagulation should be discussed
with the patient's internist, and the method of preoperative discontinuation of the
anticoagulant should be based on the estimated risk of deep vein thrombosis or emboli.
Patients in a low-risk category may simply have warfarin discontinued 1 to 2 days before
surgery and restarted approximately 5 days after surgery. Low-risk patients include those
with aortic valve prosthesis, atrial fibrillation, or a resolved cause of a previous deep vein
thrombosis. High-risk patients, such as those with a history of emboli of cardiac origin or
mitral valve disease or prosthesis, should have warfarin discontinued several days before
surgery and replaced with heparin. Intravenous heparin should be used to increase the
PTT to 1.5 to 2 times normal levels. The effect of warfarin may be counteracted with
vitamin K administration as indicated in Table 18.2. Twelve hours before surgery,
heparin should be discontinued, and the PTT will return to normal by surgery. If surgery
is imminent in a patient anticoagulated with a warfarin product, 2 to 4 U of fresh frozen
plasma may be given to correct the coagulation fac-tor deficiencies immediately while
vitamin K takes effect. Repeated PT or international normalized ratio tests should be
performed to evaluate the results of therapy. If an emergency situation arises in the
heparinized patient, protamine sulfate may be given to antagonize heparin immediately.
The timing for restarting anticoagulants postoperatively depends on patient risk factors
for thrombosis and embolization and on the type of surgery and hemostasis obtained at
surgery. In neurotologic surgery and possibly airway surgery in which bleeding would
present a life-threatening problem, anticoagulation should be delayed at least 36 to 48
hours. Rapid anticoagulation then is accomplished with intravenous heparin, whereas
slower anticoagulation is accomplished simultaneously by restarting oral warfarin.
Intraoperative and Postoperative Bleeding
The most common cause of intraoperative or postoperative bleeding problems, other than
an unsecured vessel, is a qualitative platelet disorder. Other possibilities include acute
intraoperative hemolysis, sepsis, DIC, and medications used during surgery. Routine
laboratory tests, including hematocrit, PT, PTT, and platelet count, should be performed.
A bleeding time, fibrinogen level, and fibrin degradation products should also be
obtained to help evaluate the possibility of a qualitative platelet disorder or a
consumptive coagulopathy. Increased fibrin degradation products (>8 mg/mL) occurs in
DIC, thromboembolic events, and fibrinolysis. Fibrinogen levels are below the normal
level of 200 to 400 mg/100 mL when the fibrinogen is abnormally depleted in
consumptive coagulopathy. Intraoperative treatment revolves around replacement of
blood and specific factors if a factor deficiency can be identified, meticulous hemostasis
in the operative field, and completion or abortion of the surgical procedure as soon as
possible. Fresh frozen plasma and platelets can be used in urgent situations of bleeding.
Treatment of the precipitating condition is the major therapeutic goal in DIC. In the
postoperative period, a search can be performed for specific causes while replacement
therapy is continued for persistent bleeding.
THROMBOEMBOLIC DISEASES
Deep vein thrombosis and pulmonary embolization are significant postoperative
problems. The major risk factors are immobilization, prior history of thromboembolic
disease (especially in the presence of varicose veins), oral contraceptives and estrogen
compounds, age older than 40 years, and hypercoagulable states, including
erythrocytosis, thrombocytosis, and inherited deficiencies of the substances antithrombin
III, protein C, and protein S resulting in decreased lysis of clots.
Preventive Measures
The pharmacologic methods of prevention of thromboembolic complications, such as
heparin, aspirin, or warfarin, are quite effective, but they require starting the patient on
treatment before surgery, which increases the risk of bleeding during surgery. Mechanical
preventative measures usually are used first in otolaryngology patients. Any method
designed to increase lower extremity blood return is helpful. Traditional measures include
early mobilization, leg elevation, elastic stockings, and physical therapy. A newer
innovation is the external pneumatic compression boot, which is applied to the calf and
thigh. The boot is intermittently inflated, the pressure held, and then deflated to massage
blood up from the lower extremity. These boots have been highly effective in preventing
thromboembolic disease and should be considered for any patient who may not be
mobilized early or who is undergoing a neurotologic, neurosurgical, or airway procedure
in which heparin may not be indicated for thromboembolic control. Caution with these
devices should be observed for patients who have severe peripheral arterial vascular
disease, because vascular supply to the lower extremity may be compromised.
Diagnosis
The risk of embolization from calf vein thrombosis is usually small, but thrombosis
propagation to the more proximal femoral and iliac veins markedly increases the chance
of pulmonary embolization. Accurate diagnosis of postoperative deep vein thrombosis is
difficult but important to prevent unnecessary anticoagulant therapy. A positive Homan's
sign, unexplained fever, pitting edema, and localized discomfort or discoloration over leg
veins may indicate underlying deep vein thrombosis. These signs, however, are quite
insensitive and may give little indication of a serious deep vein thrombosis. When it is
suspected, objective testing should be performed. Contrast venography, with contrast
material injected into a foot vein, is the definitive test, but it is associated with a
significant number of complications. The most accurate noninvasive test is real-time
(duplex) ultrasound, which is less sensitive to calf thrombosis than the more proximal
femoral and iliac thrombosis.
Pulmonary Embolism
Despite preventive measures, deep vein thrombosis and subsequent pulmonary
embolization may develop. The diagnosis is difficult, but pulmonary embolization should
be suspected in patients with sudden onset of tachypnea, dyspnea, chest pain, hemoptysis,
hypnoxia, or arrhythmias. A ventilation-perfusion scan is obtained. A normal result
indicates little likelihood of a pulmonary embolization, but any other result on the
perfusion scan may require the use of pulmonary angiography, depending on the degree
of risk for emboli in the patient.
Management
Anticoagulation with heparin followed by oral anticoagulants is necessary in all patients
with proximal deep vein thrombosis and pulmonary embolization. In neurotologic, skull
base, or procedures in the airway, the risk of bleeding must be considered. In other cases,
heparin should be given immediately and continued for 7 to 10 days. A loading dose of
5,000 to 10,000 U of heparin is given intravenously, followed by 1,000 to 2,000 U/h
through an infusion. The PTT should be maintained in a range of 1.5 to 2 times control.
Oral warfarin anticoagulant therapy is initiated and overlapped to maintain control. In
severe cases, streptokinase, urokinase, or recombinant tissue plasminogen activator
should be considered as thrombolytic therapy. All bleeding times are prolonged with
thrombolytic therapy, and concurrent heparin therapy should not be used. Heparin should
be started, however, after discontinuation of thrombolytic therapy, which usually lasts for
1 to 3 days. Inferior vena caval interruption is used when anticoagulation is
contraindicated or there are recurrent emboli in adequately anticoagulated patients.
ENDOCRINE ABNORMALITIES
Diabetes Mellitus
A fasting blood glucose is obtained as a routine test because the frequency of diabetes is
approximately 1% and rises to 5% of the population aged over 40 years. Surgery and
anesthesia increase production of stress hormones and worsen hyperglycemia. The aim of
perioperative care in the known diabetic is reasonable control of glucose levels in the
range of 120 to 250 mg/dL. Patients scheduled for minor surgery under local anesthesia
need no special adjustments. All other patients may require insulin coverage (Table 18.3).
Adjustments to the patient's usual treatment are guided by blood (not urine) glucose
monitoring every 1 to 2 hours at the start of surgery. It is important that diabetics receive
3 g/kg of body weight each day of carbohydrates to prevent protein catabolism and
lipolysis. Intravenous administration of 5% dextrose in water at 100 mL/h provides 5 g
glucose/h.

TABLE 18.3. INSULIN COVERAGE DURING
SURGERY



Management of poorly controlled patients must be obtained before surgery. The goal is to
lower the glucose level below 250 g/dL. Regular insulin is given at a dose of 4 to 10 U
subcutaneously every 4 to 6 hours. Alternatively, a constant regular insulin infusion can
be administered with a loading dose of 0.1 to 0.2 U/kg, followed by an infusion rate of
0.1 U/kg per hour in a 0.9% sodium chloride solution. Blood glucose levels are measured
every 1 to 2 hours. The patient then may be monitored during surgery in the same way as
the well-controlled diabetic.
In ketoacidosis, an i.v. bolus of 12 to 20 U of regular insulin is followed by constant
infusion of 5 to 10 U/h. Hyperosmolar nonketotic hyperglycemia requires lower doses of
insulin (0.05 to 0.10 U/kg hourly). In both conditions, fluid deficit is present, and
replacement with normal saline at 1 L/h is started with potassium replacement always
required and guided by serum potassium measurement.
In the immediate postoperative period, subcutaneous regular insulin is given every 2 to 4
hours, depending on serum glucose. A typical regular insulin sliding scale for
hyperglycemia control is 4 U of regular insulin for glucose levels of 200 to 250 g/dL or 6
to 8 U for glucose levels from 251 to 300 g/dL. Intravenous glucose is continued to
provide nourishment. In the later postoperative period, the patient must be continued on a
modified insulin dose and i.v. glucose until regular diet and activity is resumed. One half
to two thirds of the patient's usual daily dose of intermediate-acting insulin is given each
morning, and blood sugar is measured every 6 hours. Discharge insulin or oral
hypoglycemic agent dose depend on glucose control at the end of the patient's
hospitalization.
Thyroid and Parathyroid Disorders
Patients with hypothyroidism may undergo emergency surgery with little increase in
morbidity. For elective surgery, gradual replacement of hormone is preferred because
rapid repletion can lead to relative adrenal insufficiency and angina in patients with
coronary insufficiency. Synthetic levothyroxine with a usual daily dose of 0.1 to 0.2 mg
is the preferred replacement medication and may be given orally or intravenously in the
same dose. In severe myxedema, hydrocortisone also should be given because
adrenocorticotropin pituitary responsiveness to stress may be decreased. Free water
clearance is also diminished, and care must be taken with hypotonic intravenous
solutions.
In thyrotoxicosis, the primary concern is development of thyrotoxic crisis (i.e., thyroid
storm). Elective surgery in hyperthyroid patients should be delayed, if possible, until the
patient is in a euthyroid state. If urgent surgery must be performed in the thyrotoxic
patient, iodines, propranolol, and antithyroid drugs, such as propylthiouracil or
methimazole, should be used to reduce the risk of thyrotoxic crisis. Propylthiouracil
blocks thyroid hormone production, inhibits the conversion of thyroxine to
triiodothronine, and usually is given in an oral dose of 100 to 150 mg three times daily.
Iodides induce a transitory inhibition of thyroid hormone production and release from the
gland and decrease vascularity of the gland, which lasts 10 to 14 days. Iodides can be
given as a saturated solution of potassium iodide at a dose of five drops orally every 6
hours. Palpitations, tachycardia, and tremor can be controlled with propranolol in an
initial dose of 20 to 40 mg taken orally four times daily or 1 to 2 mg given intravenously
every 4 to 6 hours. Hydrocortisone should be given to counter relative adrenal
insufficiency.
Thyrotoxic crisis manifests by severe exaggeration of the classic symptoms of
thyrotoxicosis and may develop intraoperatively or in the immediate postoperative
period. The patient may suffer a marked fever, sweating, tachycardia, vomiting,
abdominal pain, and delirium. Large doses of the same medications are given (Table
18.4). Supportive therapy includes temperature control with acetaminophen or a cooling
blanket. Sedation and oxygen therapy may be needed, and the patient should receive
adequate glucose-containing intravenous solutions due to the high metabolic rate.

TABLE 18.4. MEDICAL CONTROL OF
THYROTOXIC CRISIS



Hypocalcemia may develop in any person undergoing thyroid or parathyroid surgery.
After either surgery, serum calcium levels should be determined every 12 hours for the
first several days, followed by daily levels thereafter. If the calcium level falls below 8.0
mg/dL, signs or symptoms of latent tetany should be sought. A positive Chvostek or
Trousseau sign, hyperreflexia, numbness or tingling in the extremities, or circumoral
paresthesias are indications to begin calcium replacement. Laryngeal stridor or overt
tetany are medical emergencies and require i.v. calcium replacement. Calcium gluconate
(10%) is less irritating than calcium chloride and is given as two ampules (20 mL) diluted
in 50 to 100 mL of dextrose solution infused over 10 minutes. Each ampule contains 1 g
of calcium gluconate and 93 mg of elemental calcium. This emergency infusion of
calcium gluconate is followed by a slow infusion of calcium gluconate, 0.5 to 2.0 mg/kg
hourly. Deficiencies in magnesium, sodium, and albumin must be excluded. The patient
should be reassured, because hyperventilation will cause a respiratory alkalosis with
resultant worsening of the hypocalcemia. Patients with prolonged hypocalcemia may
require oral calcium replacement with 1.5 to 3 g each day of elemental calcium and
vitamin D. Perioperatively, the serum calcium levels should be maintained near 8 mg/dL.
Adrenal Glucocorticoids
Adrenal insufficiency in otolaryngology patients is usually due to prior long-term steroid
use with suppression of the hypothalamic-pituitary-adrenal axis. The normal oral daily
maintenance dose of hydrocortisone is 20 mg in the morning and 10 mg in the afternoon.
Prednisone is 4, methylprednisolone is 5, and dexamethasone is 25 times more powerful
than hydrocortisone. Patients who have been on more than 5 mg of prednisone each day
for 3 weeks in the preceding year are assumed to have suppressed endogenous production
of cortisol and should be treated with supplemental steroids for surgery. Patients who are
currently on steroids, those with known adrenal insufficiencies, and even patients with
Cushing syndrome also should be covered with supplemental steroids in the perioperative
period. Large quantities of cortisol, in the range of 300 mg daily, are released from the
adrenal gland during stresses such as surgery. The dose of administered steroids is
designed to be in this same range (Table 18.5). Failure to provide replacement
glucocorticoids can result in loss of vascular tone with hypotension that is refractory to
fluids or pressor agents.

TABLE 18.5. REPLACEMENT
HYDROCORTISONE SODIUM SUCCINATE FOR
ADRENAL-SUPPRESSED PATIENTS



Primary adrenal insufficiency is rare and may present perioperatively as acute adrenal
crisis. The symptoms are not specific and can include hypotension, weakness, dizziness,
fever, nausea, vomiting, and abdominal pain. In the face of unexplained hypotension,
adrenal insufficiency must be considered and treated empirically if hypotension is
refractory. Blood should be drawn for measurement of serum levels of cortisol,
electrolytes, glucose, blood urea nitrogen, and creatinine. An immediate bolus of 200 mg
of hydrocortisone is given intravenously, followed by fluids containing glucose and
saline to correct volume deficiencies.
Pituitary
The otolaryngologist often is involved in the removal of pituitary adenomas and other
skull-base surgery. If a complete hormonal evaluation has not been performed, the
otolaryngologist should be aware of possible adrenal and thyroid insufficiency. More
common, however, is perioperative diabetes insipidus and the syndrome of inappropriate
antidiuretic hormone (ADH) secretion.
Diabetes insipidus is caused by a decreased level of ADH, which impairs free-water
reabsorption, leading to increased thirst and large volumes of dilute urine in the face of
inappropriate hyperosmolarity of the serum. In effect, the patient has a free-water deficit.
Other conditions may mimic diabetes insipidus. The stress of surgery normally increases
ADH secretion and free-water retention, resulting later in a water diuresis that may be
mistaken for diabetes insipidus. Excessive i.v. fluid replacement also may result in large
urinary volume secondary to the input. Mannitol given during neurologic and skull-base
surgery may produce an osmotic diuresis. A diagnosis of diabetes insipidus should be
restricted to patients with urinary outputs greater than 200 mL/h with associated
hypernatremia, serum hyperosmolarity, low urinary specific gravity, osmolarity, and
sodium. Urine osmolarity is usually less than 200 mOsm and urine specific gravity less
than 1.005. The patient should be monitored with frequent intake and output, body
weights, urine-specific gravity, and serum sodium osmolarity. In mild cases, simple oral
intake of water to satisfy thirst may provide adequate free water. In more severe cases or
in the patient not taking water orally, i.v. 5% dextrose in water with only enough sodium
to cover obligate sodium requirements is given. The volume should equal the urinary loss
plus insensible losses. For high urinary volumes (i.e., more than 4 L daily),
pharmacologic replacement should be considered. Overtreatment should be avoided,
especially in neurosurgical cases, to lessen the chance of water intoxication and brain
edema. Desmopressin acetate is a long-acting vasopressin analog given intranasally at a
dose of 5 to 10 mg once or twice daily, subcutaneously 1 to 2 mg daily or i.v. 0.3 g/kg
at 12- to 24-hour intervals. It must be used with caution in patients with coronary artery
disease.
Aqueous pitressin has the drawbacks of short duration of action and a vasoconstrictor
effect, which may precipitate angina. The dose is 5 U intramuscularly every 3 to 6 hours.
Usually, the condition will resolve over 3 to 5 days with conservative treatment of water
replacement and judicious use of ADH compounds.
The syndrome of inappropriate ADH secretion is characterized by hyponatremia with a
urine osmolality that is inappropriately concentrated compared with serum osmolality.
Because surgery and trauma cause ADH release, excessive administration of hypotonic
i.v. solutions should be avoided. Treatment usually is accomplished by fluid restriction or
use of demeclocycline, which inhibits the renal effects of ADH.
CARDIOVASCULAR DISORDERS
In asymptomatic patients, a routine electrocardiogram (ECG) is recommended for men
over 40 and women over 55 years. Cardiac evaluation should be done before surgery for
patients with cardiovascular symptoms such as chest pain, dyspnea on exertion,
palpitations, orthopnea, edema, or a history of ischemic heart disease, especially with
unstable angina or a myocardial infarction within the preceding 6 months, congestive
heart failure, valvular heart disease, arrhythmias, or hypertension. Besides a thorough
history and physical examination, a preoperative ECG should be obtained and compared
with any previous ECG tests. A chest radiograph, pulmonary function tests, and arterial
blood gases are performed to estimate cardiopulmonary function. If the patient is taking
cardiac medications (e.g., digitalis), serum levels should be obtained to ensure optimal
levels before surgery. Electrolytes like potassium and calcium should be measured to
attempt to decrease the likelihood of perioperative arrhythmias.
Hypertension
Antihypertensive medications should be continued to the morning of surgery and
resumed immediately postoperatively. -Blocking agents should be continued until
surgery and resumed immediately postoperatively, because sudden cessation can produce
a withdrawal syndrome with sinus tachycardia, hypertension, myocardial ischemia, or
tachyarrhythmias. The symptoms may mimic a variety of cardiac abnormalities, but they
respond rapidly to resumption of propranolol, which may be given intravenously 1 to 2
mg every 5 to 10 minutes until the condition improves. Clonidine withdrawal syndrome
can be character-ized by a hypertensive crisis that may need i.v. nitroprusside or
phentolamine for control. Monoamine oxidase inhibitors and guanethidine should be
discontinued 2 weeks before surgery because of the possibility of severe drug interactions
or interference with circulatory reflexes. Consideration should be given to withholding
diuretic therapy for 1 to 7 days before surgery to enable potassium deficits and volume
depletion to be corrected before surgery.
All anesthetic agents are vasodilators and negative ionotropes, which may create the
necessity for fluid infusion in excess of fluid losses during surgery. Pharmacologic agents
may be needed to control blood pressure during surgery. On emergence from anesthesia,
sympathetic tone in the vessels is restored and blood pressure can rise significantly.
Postoperative hypertensive events are defined as systolic blood pressure greater than 200
mm Hg, a rise in systolic blood pressure greater than 50 mm Hg, or a diastolic blood
pressure greater than 100 mm Hg.
In postoperative hypertension, it is extremely important to search for a cause rather than
simply to treat the hypertension with pharmacologic agents. The differential diagnosis of
postoperative hypertension should include hypervolemia, ventilatory or respiratory
failure, inadequate analgesia or discomfort, residual effects of anesthesia or intraoperative
pressor agents, anesthetic-induced hypothermia and shivering, distended stomach or
bladder, or manifestations of preexisting hypertension. Treatable causes of postoperative
hypertension should be corrected before pharmacologic agents are given, because severe
hypotension may result if simultaneous antihypertensive medications and treatment of the
underlying cause of hypertension are undertaken.
Prolonged or extreme postoperative hypertension may lead to myocardial failure or
increased risk of intracranial bleeding in neurotologic or skull-base procedures. In urgent
situations, the pharmacologic agent of choice is nitroprusside (Table 18.6).

TABLE 18.6. PERIOPERATIVE
PHARMACOLOGIC CONTROL OF
HYPERTENSION



Postoperative Hypotension
As in hypertension, precipitating factors for hypotension must be found and treated.
Hypovolemia secondary to inadequate fluid replacement or hemorrhage is the most likely
cause of postoperative hypotension. Others include preoperative and intraoperative
anesthetic agents and medications, pain, sepsis, cardiac dysfunction (e.g., arrhythmias,
infarction, failure), pulmonary problems (e.g., inadequate ventilation, emboli,
pneumothorax), and electrolyte abnormalities. If a central venous line is not available to
monitor intravascular volume, a fluid challenge consisting of 250 to 500 mL of normal
saline can be given over 10 to 15 minutes. Clinical examination of the jugular venous
pressure can guide replacement, and the infusion may be repeated once or twice. If no
improvement is evident, a complete cardiac and pulmonary evaluation is indicated. The
patient should have a chest radiograph, ECG, arterial blood gas sample, blood cultures if
febrile, and insertion of monitoring catheters (e.g., central venous, arterial, and
pulmonary artery lines). Vasopressor medication is indicated if significant hypotension is
present (i.e., systolic pressure less than 100 mm Hg) and the patient manifests symptoms
of decreased profusion, such as obtundation, cardiac insufficiency, or decreased urinary
output (Table 18.7).

TABLE 18.7. PHARMACOLOGIC CONTROL OF
PERIOPERATIVE HYPOTENSION



Arrhythmias
The clinician must treat an arrhythmia if it is hemodynamically significant and also must
search for the underlying cause. Acute cardiac disease, hypoxia, hypotension, acid-base
abnormalities, hypokalemia, and central venous or pulmonary artery catheter stimulation
of the heart are common causes of arrhythmias. Hypokalemia may be worsened by
intraoperative hyperventilation and resultant respiratory alkalosis and by intraoperative
fluid replacement and fluid shifts. The underlying causes of cardiac arrhythmias must be
evaluated rapidly and corrected. Some arrhythmias, such as nodal rhythm and
bradycardia, are common during general anesthesia and usually do not require treatment.
Others can be hemodynamically significant and may be tolerated poorly by a heart
already affected by the negative inotropic action of the anesthetic agent.
Supraventricular tachyarrhythmias may be treated with i.v. adenosine, verapamil,
propranolol, esmolol, or diltiazem. Intravenous digoxin may be used to control atrial
fibrillation or persistent flutter. Ventricular tachycardia is treated initially with lidocaine,
using a loading bolus dose of 1 to 1.5 mg/kg of body weight given intravenously, with a
repeat bolus of 0.5 mg/kg 10 minutes later, followed by a continuous infusion of 1 to 4
mg/min. In all cases of tachyarrhythmias, direct current cardioversion may be necessary
if severe hypotension, cardiac ischemia, or congestive heart failure and pulmonary edema
develop. Simple bradyarrhythmias (e.g., sinus bradycardia) usually respond well to
atropine. More significant bradyarrhythmias (e.g., sick sinus syndrome) need cardiac
pacing under the supervision of a cardiologist. Any of these serious bradyarrhythmias or
tachyarrhythmias will mandate observation in the cardiac care unit or with telemetry.
PULMONARY DISORDERS
General Management
Pulmonary problems are the most common complication after surgery. Anesthesia and
surgery have profound effects on pulmonary function. All lung volumes, especially vital
capacity and functional residual capacity, are decreased, reducing lung compliance and
increasing the work of breathing. The result is alveolar hypoventilation with ventilation-
perfusion abnormalities and hypoxemia. Extravascular lung water also may be increased
from increased hydrostatic pressure secondary to fluid overload and low plasma oncotic
pressure. If the pulmonary capillary endothelium also is damaged from exposure to toxic
products from injury, infection, or the surgical procedure, increased capillary
permeability may increase lung extravascular water. In otolaryngologic procedures,
impaired laryngeal protective mechanisms, airway edema, and foreign bodies such as
blood clots may promote aspiration.
Treatment is initiated in the preoperative period with preventive measures and
identification of the patients who may be at a higher risk for pulmonary problems.
Historic symptoms, such as dyspnea on exertion, cough, sputum production, and cigarette
smoking, indicate the need for further evaluation. The physical examination should
include auscultation during maximal inspiration and forced expiration. Observation of the
patient climbing stairs remains a valuable adjunct to clinical estimation of pulmonary
reserve. The preoperative chest radiograph can demonstrate pathology, but it is more
important when used for postoperative comparison. A preoperative chest radiograph in
asymptomatic patients is recommended by the American College of Surgeons for known
pulmonary or cardiac disease, age greater than 40 years, high risk for postoperative
pulmonary complications, and a positive tuberculin test or high risk for unsuspected
tuberculosis. Pulmonary function tests can give the clinician an idea of the degree of
alveolar ventilation and the ability to clear secretions in the postoperative period. The
best overall predictor of postoperative pulmonary difficulties may be the maximal
voluntary ventilation test, which is the largest volume that can be breathed by voluntary
effort per minute, extrapolated from rapid breathing into a spirometer during a 15-second
interval. This test measures lung function, compliance of the chest wall, strength of the
respiratory muscles, and patient motivation and ability to cooperate. Preoperative arte-rial
blood gases provide mainly a comparison for postoperative measurements.
Any patient with arterial oxygen tension less than 60 to 70 mm Hg usually has a
significant ventilation-perfusion mismatch. An arterial carbon dioxide tension greater
than 45 mm Hg indicates significant alveolar hypoventilation and is associated with an
increased incidence of postoperative complication. Reversible causes, such as
bronchospasm or bronchitis, should be corrected preoperatively.
Preventive measures are begun as soon as a decision to operate is made and are carried
through the entire postoperative course. Predisposing factors for lung complications, such
as smoking or obesity, and underlying pulmonary conditions, such as chronic bronchitis,
chronic obstructive pulmonary disease, and reactive airway disease, are corrected insofar
as possible before surgery. Ideally, pulmonary exercises that will be performed
postoperatively should be practiced before surgery. These include deep breathing and the
use of incentive spirometry. The main thrust of postoperative care is deep-breathing
exercises to enhance alveolar aeration and ventilation. Unless secretions are a major
problem, coughing may not need to be encouraged and may be detrimental in skull-base
procedures with an increased chance of a spinal fluid leak.
The choice of anesthesia is important. Although local anesthesia may seem preferable,
general endotracheal anesthesia gives the best control over the airway. Frequent sustained
inflation to 20 mL/kg or to an airway pressure of 30 cm H
2
O should be performed to
prevent alveolar collapse. Intravenous crystalloid solutions should be given
conservatively, and blood or plasma replacement products should be given with large
fluid losses to help maintain normal intravascular colloid pressure and prevent pulmonary
edema.
Preventive measures should be continued in the postoperative period. The endotracheal
tube should be kept in place as long as necessary to maximize alveolar ventilation.
Immediately after endotracheal tube removal, deep-breathing exercises, clearance of
respiratory secretions, and frequent turning of the patient are begun. If the patient is
unable to perform maximal inhalation exercises or incentive spirometry, continuous
positive airway pressure or intermittent positive pressure breathing may be of help in
preventing atelectasis.
Management of Postoperative Pulmonary Insufficiency
Atelectasis, pulmonary edema, and aspiration are the most common causes.
Exacerbations of preexisting pulmonary problems, mechanical limitations of breathing,
acute bronchospasm, pulmonary embolization, congestive heart failure, and hypovolemia
also should be considered. In head and neck procedures, mechanical limitations to
breathing may be caused by gastric distension, pneumothorax, aspiration, or phrenic
nerve injury with hemidiaphragmatic paralysis. Supplemental oxygen should be given
immediately at 10 to 20 L/min while a pertinent history, physical examination, arterial
blood gases, and a chest radiograph are obtained. The patient should be in a comfortable
sitting position.
Treatment of atelectasis is aimed at reexpanding the collapsed segment. Deep-breathing
exercises, incentive spirometry, continuous positive airway pressure, and intermittent
positive pressure breathing can be used. Adequate pain medication should be provided to
promote mobility and deep breathing. Increased hydration, mist, nebulized
bronchodilators, and mucolytic agents should be given through the airway to liquefy
thickened secretions that may be blocking the involved bronchus. Paradoxically,
coughing does not clear mucus from collapsed airways, because there is no air distal to
the mucous plug. Tracheal suction may be successful in removing retained secretions but
should be performed with caution because it may produce increased vagal tone and
hypoxemia. Five milliliters of saline may be injected through the nasotracheal catheter to
help liquefy secretions and facilitate aspiration through the catheter. Suction should be
applied for no longer than 10 seconds before oxygen flow is resumed to prevent cardiac
arrhythmia.
ECG monitoring should be performed and atropine should be available for bradycardia.
Bronchoscopy allows direct visualization of the bronchial tree, removal of debris, and
culture. If adequate ventilation cannot be restored by these methods, endotracheal
intubation and mechanical ventilation are indicated.
Otolaryngology patients undergoing major head and neck ablative procedures are
predisposed to aspiration of saliva, blood, or gastric acid. Immediate treatment consists of
mechanical removal of any foreign substance from the upper airway. Nasogastric tube
placement is performed to empty the stomach of any further gastric acid. Bronchospasm
may be present and respond to bronchodilators. Endotracheal intubation is performed if
pulmonary insufficiency results.
Pulmonary edema is caused by an increase in lung water. A flow-directed pulmonary
artery catheter can help distinguish high from low pressure pulmonary edema.
Cardiogenic pulmonary edema is usually associated with a pulmonary artery wedge
pressure greater than 25 mm Hg. In cardiogenic pulmonary edema, interstitial edema
progresses to alveolar edema. Treatment in young patients is fluid restriction with the use
of diuretics as necessary. In patients with cardiopulmonary or renal disease, dobutamine,
dopamine, or both may be required for low cardiac output and to increase renal perfusion.
Furosemide is the diuretic of choice because it promotes venodilation and diuresis.
Nitroprusside may be necessary in patients with high systemic vascular resistance to
reduce the cardiac afterload. Intravenous nitroglycerin may help patients who have
coronary insufficiency. If hypoxemia or hypercapnia persists after these measures,
ventilatory support may be necessary.
Adult respiratory distress syndrome is manifest as pulmonary edema in the presence of
normal pulmonary artery wedge pressure. Lung damage is indirect and usually caused by
infection, inflammation, or tissue destruction elsewhere in the body. It manifests as
severe hypoxemia and decreased lung compliance, and it shows diffuse bilateral
pulmonary infiltrates on chest x-ray. Management is directed at treating the underlying
cause. The severe hypoxemia and hypercapnia may need mechanical ventilation with
positive end-expiratory pressure. The inspired oxygen content should be kept as low as
possible to minimize oxygen toxicity while maintaining the hemoglobin oxygen
saturation above 90%. Intravascular volume is kept low, and dobutamine and dopamine
may be needed for inotropic support. Nitrous oxide may reduce the pulmonary arterial
pressure and improve oxygenation.
GASTROINTESTINAL DISTURBANCES
Stress Ulcers
In patients who do not have a history of peptic ulcer disease, the most common cause of
postoperative upper gastrointestinal bleeding is stress ulceration of the gastric mucosa.
These ulcers develop as a result of trauma, surgery, or the stress associated with severe
illness. The ulcers are usually painless, and the clinical presentation may be limited to a
bloody aspirate from an indwelling nasogastric tube, melena, or an unexplained fall in
hematocrit. The most reliable method of diagnosis is gastric endoscopy to visualize the
shallow ulcerations, which are usually confined to the proximal part of the stomach.
The main thrust of management should be prevention, and prophylactic measures should
be considered in all major head and neck cases. Prevention of stress ulceration is aimed at
reducing gastric acidity (above pH of 4 to 5), which may be accomplished by antacids or
histamine-receptor blockers, such as cimetidine or ranitidine. The i.v. dose of cimetidine
is 50 mg/h or 300 mg every 6 hours, and the dose for ranitidine is 6.25 mg/h or 50 mg
every 8 hours for the continuous or bolus injections, respectively. A continuous i.v.
infusion is more effective than bolus injections. Cytoprotective agents, such as sucralfate
suspension, maintain the integrity of the stomach mucosal barrier. The dose is 1 g in 10 to
20 mL of sterile water infused into the stomach every 6 to 8 hours via nasogastric tube.
If stress ulcers develop, treatment methods are similar to those used in prophylaxis.
Emergencies (e.g., hypovolemia) must be managed immediately with fluid or blood
replacement. For massive bleeding, a large-bore nasogastric tube is placed to decompress
the stomach, monitor gastric pH, and provide access for antacid therapy and cooled saline
irrigations. Intravenous cimetidine or ranitidine is given. Angiography with selective
injection of vasopressin has been used. Arterial embolization or gastric endoscopy with
electrocauterization or laser photocoagulation may be attempted. Surgical intervention
may be necessary in patients with persistent bleeding or ulceration despite conservative
therapy.
Adynamic Ileus
Ileus is much more common after abdominal procedures than after head and neck
procedures. The otolaryngologist, however, must certify that there is intestinal motility
before beginning postoperative feeding, especially hyperosmolar tube feeding. Adynamic
ileus should be suspected in any patient with constipation, prolonged vomiting,
abdominal pain and distention, or an absence of bowel sounds. Abdominal radiographs
show a diffuse gas pattern and distended loops of bowel. The most common cause is the
perioperative administration of pharmacologic agents, including anesthetic agents,
opioids, anticholinergics, calcium channel blockers, and antihistamines. The differential
diagnosis must include hypokalemia, distal obstruction (e.g., fecal impaction, neoplasm),
sepsis, and an acute abdominal event, such as exacerbation of diverticulosis. Endoscopy
or contrast enema may be necessary to rule out bowel obstruction. The treatment is
directed at the underlying cause. The patient usually responds to supportive measures of
avoidance of oral intake, administration of i.v. fluids, and nasogastric suction.
Sympathetic blockade or parasympathetic stimulation with bethanechol, neostigmine, or
metoclopramide is currently being researched. With these measures, the ileus usually
resolves within a period of several days.
Diarrhea
The most significant exudative diarrhea is antibiotic-associated diarrhea and colitis. The
severity of antibiotic-related diarrhea varies from mild diarrhea to pseudomembranous
colitis with severe systemic manifestations. Antibiotics frequently used in otolaryngology
patients may precipitate the syndrome. Clindamycin and ampicillin are the most common
causes, but cephalosporins, erythromycin, penicillin, and trimethoprim-sulfamethoxazole
also have been implicated. With persistent diarrhea, a stool examination is paramount.
Pus suggests a bacterial infection or an antibiotic-associated pseudomembranous colitis.
The stool should be evaluated for enteric pathogens, intestinal parasites, and Clostridium
difficile. More than 90% of patients with antibiotic-associated pseudomembranous colitis
test positive for C. difficile toxins.
Management is both supportive and specific. Fluid and electrolyte balance must be
monitored closely and may require measurement of electrolyte levels in stool samples.
Potassium and bicarbonate losses may be large and may require i.v. replacement with up
to two ampules of sodium bicarbonate in each liter of 5% dextrose in water. If cessation
of the causative antibiotic does not relieve diarrhea, then treatment with appropriate
antibiotics is guided by stool culture. Vancomycin (125 to 500 mg orally four times
daily) or metronidazole (250 mg orally three times daily) are given for 7 to 14 days for
patients who tolerate oral intake. Both medications may be given intravenously with a
dose of 500 mg every 6 hours. Antiperistaltic medicines should be avoided because
decreased intestinal motility promotes bacterial overgrowth. Other causes of diarrhea
such as osmotic, secretory, and altered intestinal motility should be considered if
resolution is not prompt.
RENAL DISEASE
Two considerations are important in the perioperative management of renal disease. The
first is treatment of patients with known renal disease, and the second is the prevention or
recognition of acute renal failure in the postoperative period.
Chronic Renal Failure
Dialysis (renal replacement therapy) must be continued before and after surgery to
minimize uremic complications such as acid-base, fluid, and electrolyte imbalances. In
the elective situation, the patient is dialyzed on the day before and the day after surgery,
usually against a low-potassium bath. The surgeon must take into account the need for
heparin as an anticoagulant during dialysis.
Other problems specific to chronic renal failure should be addressed. Baseline
hematocrits in the 20% to 25% range should be adequate for surgery unless large blood
losses are expected. Platelet dysfunction in renal disease is corrected only partially by
dialysis. In patients with active bleeding, administration of desmopressin acetate at a dose
of 0.3 mg/kg should be considered. Hypertension should be controlled with diuretics and
dialysis, if necessary, for restoration of normal intravascular volumes. Electrolyte
abnormalities are discussed in other chapters in this volume.
An effort should be made to avoid medications with known renal toxicity, including
anesthetic agents. Whereas methoxyflurane and gallamine should be avoided, halothane
can be used as an inhalation agent. The neuromuscular blockers pancuronium and
tubocuraine are contraindicated.
Intraoperatively, the goal should be to prevent further kidney damage. An effort should
be made to optimize renal profusion by correcting volume deficits and maintaining
adequate cardiac output. In patients who are not anuric, urinary output should be
maintained at a level of at least 0.5 mL/kg per hour. Renal blood flow can be augmented
with low-dose dopamine (15 mg/kg per minute). Diuresis can be stimulated with
mannitol or a loop diuretic like furosemide in an effort to maintain preoperative urine
outputs.
After surgery, fluids, electrolytes, acid-base balance, and hematocrit should be watched
closely. In severe abnormalities, urgent hemodialysis may be necessary despite the need
for heparin. Chronic renal failure patients may develop postoperative congestive heart
failure secondary to ischemic heart disease or hypotension secondary to volume
depletion, decreased cardiac output, or abnormal receptor function. Nutritional support
with a diet high in carbohydrates and essential amino acids is important. Adequate caloric
intake (35 to 50 kcal/kg daily) is provided to avoid endogenous protein catabolism.
Protein is restricted to 0.6 to 0.7 g/kg daily of high-biologic-value protein. Prophylactic
antibiotics and careful wound management are indicated because of decreased immune
function.
Acute Renal Failure
Acute renal failure is an acute decrease in renal function and glomerular filtration rate.
Diminished urine output (i.e., less than 0.5 mL/kg each hour or less than 400 mL/day in
adults) should prompt an investigation to eliminate renal causes. Difficulty in voiding,
with resultant urinary retention, may be caused by perioperative medication. Placement
of a bladder catheter may be necessary to relieve urinary retention and to monitor
adequate urinary output. Continued low urinary output through the bladder catheter
demands immediate action to prevent renal damage and acute renal failure. Prerenal
hypovolemia or hypotension are the most common causes of low urine volume in head
and neck surgery patients. The urine is low in volume, sodium, and chloride and high in
osmolarity. Clinical assessment should be used to differentiate between hypovolemia and
decreased cardiac function. In hypovolemia, treatment should be directed toward
increasing renal perfusion by rapid infusion of i.v. fluids to raise the central venous
pressure to at least 10 mm Hg. The i.v. fluid bolus should be approximately 10% of
circulating blood volume; commonly, it is 500 to 1,000 mL of normal saline. Blood may
be used for this bolus if there has been significant blood loss during surgery. There is
controversy concerning the use of diuretics and osmotic agents such as mannitol because
they have not been shown to decrease the mortality from renal failure. Administration of
these agents decreases the use of urine volume and electrolytes as a measure of renal
function. However, diuretics can convert an oliguric to a nonoliguric renal failure, which
may have a higher survival rate. If diuretics are used, 40 mg of furosemide is
administered intravenously with observation for increased urinary output over the next 60
minutes. Low-dose dopamine may be preferred to augment renal profusion and
glomerular filtration rate.
The most common postoperative intrinsic renal cause of acute renal failure is acute
tubular necrosis secondary to ischemia or nephrotoxicity. Urinalysis demonstrates a
hypoosmolar urine with a high sodium content and a low urinary-to-plasma creatinine
ratio. Examination of urinary sediment demonstrates classic pigmented granular casts.
After a tentative diagnosis of acute tubular necrosis or other renal cause of acute renal
failure is made, baseline laboratory and clinical values, such as body weight, blood
pressure, chemistry and hematologic profile, urinary chemistry and sediment
examination, and consideration for renal imaging studies or sonography, should be
performed. Early nephrology consultation should be obtained. Conservative management
may be successful with a high-carbohydrate low-protein diet, fluid and electrolyte
management, and careful reevaluation of all medications. If uremia develops, dialysis is
necessary.
NEUROPSYCHIATRIC PROBLEMS
Postoperative Seizures
The goals of therapy for postoperative seizures are to control the seizure and to determine
the underlying cause. Typical seizures in patients with known seizure disorders may
simply require supportive measures and continuation of anticonvulsant medications.
Atypical seizures in a known seizure patient or new seizures in a previously
asymptomatic patient require immediate investigation for a treatable underlying cause.
Metabolic imbalances such as hyperglycemia or hypoglycemia, hypoxia, acid-base
disturbances, hypernatremia or hyponatremia, or other electrolyte abnormalities may
cause seizures. Head trauma, stroke, subarachnoid hemorrhage, central nervous system
infections, drug and alcohol withdrawal, cardiac arrhythmias, hypotension, and certain
drugs and toxins can precipitate a seizure. Overdosage of cocaine and local anesthetics
like lidocaine are of particular concern to the otolaryngologist. The patient's history
should highlight any previous neurologic disease, possible drug reactions, and fluid and
electrolyte abnormalities. Complete general and neurologic and physical examinations
should be performed. Characteristics of the seizure also should be noted. If the seizure is
self-limited, the laboratory evaluation should include a complete blood count, blood
chemistries, ECG, electroencephalogram, lumbar puncture, and an imaging study of the
head with contrast.
Status epilepticus is the condition of continuous or repeated seizures, usually lasting
longer than 30 minutes, and is a true medical emergency. The condition produces
acidosis, hypotension, relative hypoglycemia, rhabdomyolysis, autonomic and
cardiovascular dysfunction, and may produce cerebral damage from local
hypermetabolism and prolonged hypoxia. An abbreviated search for underlying causes is
important, but the primary goals are to stop the seizure, maintain the airway and
ventilation, avoid hypoxia, and avoid complications, such as an injury to the operative
site. An i.v. drip is started, and blood should be drawn for the aforementioned tests.
Serum anticonvulsant drug levels and arterial blood gases also should be tested.
Metabolic and ventilation abnormalities should be corrected. Pharmacologic control is
obtained with benzodiazepines, phenytoin, and barbiturates (Table 18.8). Because high
doses may be required, the clinician should be ready to support ventilation. The duration
of action of diazepam is relatively short: about 20 minutes. Lorazepam also may be used,
and the duration of action is somewhat longer. Phenytoin should be used in addition to
the benzodiazepines or as the only therapy. There is no significant central nervous system
depression, but rapid administration may cause cardiovascular toxicity. The longer
duration action of phenytoin supplements the initial control obtained by the
benzodiazepines. Phenobarbital also can be used, but it leads to depression of
consciousness and respiration. Blood levels should be checked to monitor treatment
levels. For patients refractory to i.v. medications, general anesthesia may be used to
control the status epilepticus. In this situation, long-acting anticonvulsants also should be
administered.

TABLE 18.8. PHARMACOLOGIC MANAGEMENT
OF STATUS EPILEPTICUS



Myasthenia Gravis
Multiple factors may increase muscular weakness in patients who have myasthenia gravis
in the perioperative period. Anticholinesterase preparations like pyridostigmine or
neostigmine should be maintained preoperatively and reinstituted on the first
postoperative day. Certain medications, including quinidine, curare, lithium, -adrenergic
blockers, phenytoin, and aminoglycoside antibiotics may increase weakness and should
be avoided. Vital capacity can be used to monitor pulmonary function. Increased
weakness of the respiratory muscles may be caused by surgical stress and may require
assisted ventilation or tracheostomy. Corticosteroids or immunosuppressive agents can be
used because the therapeutic benefit in myasthenia gravis may not be seen for several
weeks or months.
Cognitive Impairment
Cognitive function or general mental status may decrease after surgery. Patients aged
over 60 years or who have addictions to alcohol or drugs, major organ system disease,
preexisting or family histories of psychosis, or even auditory or visual impairment are
predisposed to perioperative cognitive impairment. Even a simple otologic procedure
with a mastoid head dressing may prevent the use of hearing aids and glasses and add to
disorientation. The entire hospital environment of sensory overload, sleep deprivation,
anxiety, and pain contribute to disorientation and decreased cognitive function.
Underlying medical conditions should be treated promptly, routine medications
continued, excessive use of long-acting benzodiazepines (e.g., diazepam) avoided, and a
comfortable hospital routine established.
An attempt should be made to classify the type of cognitive impairment. Delirium should
be differentiated from dementia, depression, mania, and other organic brain disorders.
Dementia is a clinical syndrome that has a protracted course and is characterized by loss
of cognitive abilities, personality disorganization, and decreased ability to perform daily
activities without disturbance of consciousness. It is usually present in the elderly (e.g.,
Alzheimer disease) with a presumed organic cause. Depression, mania, and other
functional disorders (e.g., schizophrenia) are true psychiatric disorders. The
otolaryngologist is more likely to see delirium, a transient organic mental disorder
characterized by global impairment of cognitive functions and resulting from diffuse
brain cell metabolic dysfunction. It is usually preceded by a lucid period of several days
after surgery before the onset of symptoms. Restlessness, insomnia, irritability,
frightening dreams, difficulty in thinking, disturbed consciousness, urinary incontinence,
focal neurological signs, nystagmus, and loss of motor coordination all are seen in
delirium. Causes of delirium can include drug intoxication, drug withdrawal, metabolic
disturbances, acute cerebral disorders (e.g., stroke, transient ischemic attack), infections,
hemodynamic disturbances (e.g., hypovolemia, congestive heart failure), respiratory
disorders, nutritional and vitamin deficiencies, and trauma. Psychiatric consultation may
be necessary to help differentiate the type of cognitive impairment and guide the
discovery of underlying causes.
Communication with and management of the patient in delirium is difficult. Agitation is
pronounced. Conservative therapy can include removal of known precipitating factors,
orientation to the environment with special attention to the use of a hearing aid and
glasses, and pain control. If reassurance is not sufficient, medications may be necessary
(Table 18.9).

TABLE 18.9. PHARMACOLOGIC MANAGEMENT
OF DELIRIUM



A continuing search for an underlying cause or management of a known cause of
delirium or agitation should be accomplished. The patient should be reassured constantly
because the experience is terrifying for patients who fear losing their mind. The
physician should watch for impending suicide and dangerous behavior, such as
wandering.
GENERAL CONSIDERATIONS
Postoperative Fever
Body temperature is set by the thermoregulatory center in the hypothalamus. When
abnormalities occur that cause the baseline body temperature to be set higher than
normal, this increased body temperature is maintained by limiting heat loss from the body
by vasoconstriction and increasing heat production by mechanisms such as shivering.
This explains why patients with new extremely elevated body-set temperatures feel cold
even in the environment of a mildly elevated temperature. If the current body temperature
is less than the elevated set-point, the patient feels cold, vasoconstricts, and shivers in an
effort to raise body temperature to the new temperature set-point.
Although common, inflammation and infection are not the only causes of postoperative
temperature elevation. Numerous noninfectious factors may cause temperature elevation,
especially in the first 48 hours after surgery (Table 18.10). Inflammation and infections
cause fever by the release of pyrogens, which elevate the hypothalamic temperature set-
point. Infectious causes of fever usually occur 2 to 4 days after surgery, somewhat later
than noninfectious causes (Table 18.10).

TABLE 18.10. POSTOPERATIVE CAUSES OF
FEVER



Evaluation of the postoperative fever should include a complete history and physical
examination rather than the usual format of blindly ordering cultures from the most
common infectious sites. The first step should be a repeat rectal temperature to evaluate
core body temperature. It is difficult to give an absolute definition of fever, but any
elevation of 1 to 2C that occurs over a short period or an absolute elevation over 38.5C
(101.3F) should be investigated. In the physical examination, special attention should be
paid to the wound, chest, and extremities to detect signs of deep venous thrombosis. The
following procedures should be performed if no obvious site is found: a leukocyte count
and urinalysis; Gram stain of sputum, urine, and wound exudate; cultures of sputum,
urine, wound, and blood; chest radiograph; and removal and culture of intravenous
catheters. Consideration should be given to examination and culture of spinal fluid. In
general, the history, physical examination, and a few selected tests should suffice to
evaluate the febrile patient. The clinician should not forget that unexplained fever in the
postoperative period is common and does not mean an infection is impending.
Treatment is based on the underlying cause and an understanding of the physiology of
temperature regulation. Correctable lesions, such as wound infections or pneumonia,
should be treated by drainage or appropriate antibiotics. If no obvious cause is discerned
or while waiting for laboratory confirmation, treatment is directed toward lowering body
temperature and the comfort of the patient. Mild temperature elevations are usually well
tolerated and do not require specific treatment. Elevations over 39C (102.2F) may be
accompanied by tachypnea, tachycardia, and malaise. In this situation, the body
temperature set-point should be lowered by antipyretics (e.g., aspirin, acetaminophen,
ibuprofen) before using other methods, such as removing bed covers, cool or ice-water
sponge baths, lowering room temperature, or increasing air flow over the patient. If the
body set-point is not lowered by the antipyretics before these adjunctive measures are
used, counterproductive vasoconstriction and shivering will attempt to maintain the
elevated temperature set-point. Other abnormalities, such as electrolyte imbalances,
should be corrected, and an adequate supply of glucose to meet the higher metabolic
demands of the fever should be administered.
In life-threatening elevations of body temperature (greater than 40C or 104F), special
attention must be given to the cardiorespiratory reserve. Pharmacologic cardiac support
and intubation should be considered. Rapid cooling of the body temperature can be
achieved by placing the patient in an ice bath or even on partial cardiopulmonary bypass
with a heat exchanger if necessary.
Malignant Hyperthermia
Malignant hyperthermia occurs in anesthetized patients and is highly lethal. Because
there is a genetic predisposition, all preoperative patients should be asked whether any
family relative has had the condition. In malignant hyperthermia, increased intracellular
levels of calcium are present in skeletal muscle, causing a sustained contraction with
increased oxygen consumption and heat production. Patients with the condition are
sensitive to the inhalation agents (e.g., halothane) and the muscle relaxant
succinylcholine chloride. Signs occur shortly after the onset of anesthesia (Table 18.11).
The specific treatment is dantrolene sodium, which inhibits the release of calcium in the
endoplasmic reticulum of the skeletal muscle. Marked hyperkalemia from potassium
released from muscle cells may need urgent treatment.

TABLE 18.11. TREATMENT OF MALIGNANT
HYPERTHERMIA



Postoperative Pain
Postoperative pain is often inadequately controlled as a result of a variety of factors,
including fear of side effects (e.g., respiratory depression, nausea), fear of addiction, or
failure to give medicine as prescribed. The otolaryngologist should give consideration to
pain control in the preoperative and postoperative periods. A complete explanation of the
procedure to the patient can alleviate anxiety that contributes to pain. Continuing concern
and reassurance postoperatively are also important in the psychologic management of
pain relief.
Pharmacologic treatment of postoperative pain revolves around the administration of
systemic opioids. Patient-controlled analgesia is an increasingly popular method of
delivering postoperative pain relief without the delay associated with formulating i.v. or
intramuscular injections. Morphine remains the drug of choice for analgesia in severe
pain. Meperidine and codeine are frequently used in otolaryngology, but methadone and
buprenorphine also can be considered. Buprenorphine is a mixed narcotic agonist and
antagonist that has a longer duration of action than morphine. To be effective, systemic
opioids must be given in adequate dosage in the immediate postoperative period.
Consideration should be given to i.v. administration, which is more reliable than
intramuscular or oral administration (Table 18.12). The principal side effect in the
postanesthetic period is respiratory depression, and it may be particularly pronounced in
elderly patients. Respiratory depression can be treated with 0.4 mg of naloxone given
intravenously. In a mixed agonist-antagonist like buprenorphine, naloxone may have less
effect, and 1.0 to 1.5 mg/kg of doxapram given intravenously is preferable. Opioids may
cause vasodilatation and secondary hypotension, which can usually be treated by
elevation of the feet.

TABLE 18.12. PHARMACOLOGIC
MANAGEMENT OF POSTOPERATIVE PAIN



NSAIDs can play an important adjunctive role in postoperative pain relief. The
combination of NSAIDs and opioid potentiates analgesia. NSAIDs are antiinflammatory,
antipyretic, and decrease platelet adhesion, which has a beneficial effect on the
prevention of deep venous thrombosis. The side effect of gastrointestinal bleeding is
minimal, but it is a concern. In most otolaryngology operations, the routine use of
NSAIDs should be considered (Table 18.12). Other adjunctive procedures, such as
transcutaneous electrical nerve stimulation, cryoanalgesia, and epidural-intrathecal opioid
administration, are treatment modalities used in other specialties but less frequently in
head and neck surgery.
Surgery in the Chemically Dependent
No attempt to withdraw the addict should be made during the perioperative period.
Instead, the medical treatment should be designed to support the addicted patient.
Narcotic analgesics should be used for pain control in the immediate postoperative
period. Thereafter, support can be maintained by a number of different withdrawal
schemes. Clonidine, 0.2 mg orally initially followed by 0.1 to 0.2 mg every 8 hours, helps
minimize the opiate abstinence syndrome. As an alternative, methadone 10 to 30 mg
orally or intramuscularly is given initially with subsequent doses every 8 to 12 hours,
depending on symptoms. Naloxone should be available and given for any drug addict
who has a sudden respiratory arrest.
The alcoholic has several specific abnormalities that should be addressed. In the
noninebriated state, the alcoholic tends to require large doses of benzodiazepines for
delirium tremor control and large doses of anesthetics. Hemostasis in the alcoholic
patient can be altered significantly. The patient may have prominent bleeding problems
secondary to insufficient or abnormal platelets found in alcoholism. Metabolic problems
are also important in alcoholic patients, who are especially susceptible to hypoglycemia
due to depleted lactogen stores. For this reason, all preoperative alcoholic patients should
have i.v. fluids with glucose before surgery. They should have a minimal fasting period
before surgery. Deficiencies in thiamine, folate, and vitamin B
12
should be evaluated and
treated. All alcoholic patients should receive 20 mg of i.v. thiamine, followed by 100 mg
given intramuscularly daily for 3 days. Phosphate and magnesium are frequently low and
should be measured and replaced as necessary.

HIGHLIGHTS
Routine preoperative laboratory evaluation is usually
unproductive in healthy patients, has minimal predictive value
for postoperative complications, and should be tailored to
evaluate known medical conditions.
Correction of hemostatic disorders requires the replacement of
specific clotting factors, fresh frozen plasma, or platelets rather
than use of whole blood.
Prevention is the best form of therapy for deep vein thrombosis,
and it involves mechanical methods more often than low-dose
heparin therapy.
In the diabetic, it is important that adequate carbohydrates are
provided during and after surgery to prevent protein catabolism
and lipolysis. During surgery, serum glucose is controlled by
monitoring blood glucose and giving supplemental regular
insulin as needed.
Thyrotoxic storm is treated with medications to block
production or release of thyroxine (e.g., propylthiouracil,
iodides), control cardiac symptoms (e.g., propranolol if
tachycardia, diuretics and digitalis if heart failure), and replace
other deficiencies (e.g., hydrocortisone).
A search for the underlying cause for postoperative hypotension
or hypertension should be sought rather than instituting
treatment only with pharmacologic agents.
Stress ulceration is the most common cause of postoperative
gastrointestinal bleeding. Reduction of gastric acidity by
antacids and histamine blockers is the most effective
prophylactic measure.
The most important intraoperative consideration in chronic
renal failure is to maximize renal perfusion and minimize
further kidney damage.
The primary goals in treating postoperative seizures are to stop
the seizure, avoid hypoxia, and avoid injury to the operative
site. Benzodiazepines, phenytoin, and phenobarbital are
pharmacologic agents of choice.
Noninfectious causes of postoperative fever are common,
especially in the immediate postoperative period
BIBLIOGRAPHY
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hyperthermia susceptibility. Anesth Analg 2000;90:200.
Breslow MJ, Miller CF, Rogers M. Perioperative management. St. Louis, MO: Mosby, 1990.
Condon RE, Nyhus LM, eds. Manual of surgical therapeutics, 9th ed. Boston: Little, Brown and Company,
1996.
Coussons TR, McKee PA, Williams GR, eds. Medical care of the surgical patient, 4th ed. Boston: Little,
Brown and Company, 1990.
D'Amico TA, Pruitt SK, eds. Handbook of surgical intensive care, 4th ed. St. Louis, MO: Mosby, 1995.
Ewald GA, McKenzie CR, eds. Manual of medical therapeutics, 28th ed. Boston: Little, Brown and
Company, 1995.
Jacober SJ, Sowers JR. An update on perioperative management of diabetes. Arch Intern Med
1999;159:2405.
Satyanarayana R, Klein S. Clinical efficacy of perioperative nutrition support. Curr Opin Clin Nutr Metab
Care 1998;1:51.
Welling DB, Thomas R, Slater P, et al. Preoperative antibiotics and steroids in vestibular Schwannoma
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

19 GERIATRIC OTOLARYNGOLOGY
Head & Neck SurgeryOtolaryngology
19




GERIATRIC OTOLARYNGOLOGY
BYRON J. BAILEY

B.J. Bailey: Department of Otolaryngology, University of Texas Medical Branch at Galveston, Galveston,
Texas.

Biology of Aging
Epidemiology and Demography
Hearing, Presbycusis, Hearing Aids, and Assistive Devices
Tinnitus
Dysequilibrium and Ataxia of the Elderly
Voice Disorders in the Elderly
Olfaction and Gustation in the Elderly
Geriatric Sinusitis and Nasal Symptoms
Presbyphagia
Peripheral Nerves
Geriatric Immunology
Benign and Nonsquamous Neoplasms
Squamous Cell Carcinoma
Facial Plastic Surgery in the Elderly
Skin Changes of Aging
Airway Management
Facial Fractures
Chapter References
Otolaryngologists-head and neck surgeons play a major role within the broad field of
geriatrics. Our involvement in caring for the elderly requires us to be willing to become
knowledgeable in the following diverse areas:
1. Preventing premature death by early detection of head and neck cancer, improved
management of trauma, and programs directed at cessation of smoking and
alcohol consumption;
2. Preventing disability, particularly through programs of hearing conservation and
the improved treatment of hearing loss;
3. Controlling and managing annoying to disabling symptoms such as nasal
congestion, chronic sinusitis, tinnitus, and vertigo;
4. Treating common and usually benign diseases such as upper respiratory
infections, acute sinusitis, otitis media, and pharyngitis;
5. Managing conditions that limit mobility and promote isolation among the elderly,
such as hearing loss, dysequilibrium, and voice changes;
6. Improving the quality of life with, for example, facial plastic and reconstructive
surgical techniques;
7. Treating conditions that can be fatal such as head and neck cancer;
8. Providing informed participation in societal deliberations concerning social and
economic aspects of the disproportionate growth of the elder segment of our
population.
This chapter provides an overview of many problems that arise within our specialties. In
addition to the brief comments about each of these areas, more detailed information is
provided in other chapters throughout this book regarding specific areas of concern.
BIOLOGY OF AGING
The belief that biologic aging is a universal property of all living things can be accepted
only with certain qualifications (1). What we call aging is the sum of many phenomena
that occur after sexual maturation in any animal: disease, environmental insult, injuries,
nutrition, and genetic programming. Normal age changes, such as graying and loss of
hair, skin sagging and wrinkling, reduced stamina, menopause, presbyopia, and loss of
short-term memory, are not diseases because they do not increase directly our
vulnerability to death. By contrast, the decrements of our immune system are normal age-
related changes that pose significant health threats such as infection and cancer.
The etiology of aging is not fully understood. In a cell culture system, the ability of
human and animal cells to replicate and function has a finite limit (2). Cells obtained
from the tissue of human embryos have been observed to undergo about 50 10
doublings before the culture is lost. Unusual strains of immortal cells may arise
spontaneously or may be created (e.g., by exposure to radiation, chemicals, or viruses).
Although these cell lines appear to deviate from the laws of finite limits to replication,
they are not truly immortal normal cells. They differ from normal cells in their
chromosome number, morphology, or banding pattern. Most of these immortal cell
populations produce tumors when they are inoculated into experimental animals of the
same species.
Cell culture studies have shown that the following exist:
1. An inverse relationship between the age of the donor and the number of doublings
that will occur in cell culture;
2. A direct relationship between the maximum lifespan of an animal's species and
the number of population doublings of its cultured cells (species-specific
regulation of longevity at the cellular level);
3. A memory within cultured cells that survives their being frozen at subzero
temperatures. (When the frozen cells are thawed much later, they complete the
usual number of population doublings and are then lost.)
Another theory of aging, the somatic mutation theory, states that a sufficient number of
mutations will occur in the replication of somatic cells to bring about the aging of
individuals. As these mutations accumulate, a progressive decrement in function will
advance through aging to death. The error theory of aging postulates that replication of
cells is associated with random errors in the important repeated DNA sequences that are
fundamental to cellular function. The accumulation of these DNA errors over time is
proposed as the basis for aging changes and eventually for the death of the organism.
The program theory of aging hypothesizes that a purposeful sequence of events is written
into the genome. As this genetic message is expressed, the organism moves through
stages of growth, development, aging, and death. This theory is currently being
aggressively investigated.
EPIDEMIOLOGY AND DEMOGRAPHY
The United States (like many other countries) is experiencing unparalleled growth in the
number of older people (3). About 29 million people in this country over the age of 65
make up approximately 12% of the population. By the year 2020, this number will
increase to an estimated 54 million people, who will make up approximately 18% of the
total population. The fastest growing segment of our population is the group 85 years and
older. Today, the United States ranks second in the number of people older than 80 years
(China is first), and by the year 2020, it has been projected that the age group greater than
60 years will grow by almost 70%.
As people live longer, they accumulate various major chronic health problems (Fig.
19.1). Even those elderly who are not in nursing homes experience serious problems just
accomplishing the everyday tasks of life (Fig. 19.2). Because of their heightened levels of
illness, elderly people use the health care system and expend health dollars far out of
proportion to their numbers (Fig. 19.3), and economists project that these figures will rise
far above current levels during the next 30 years (Fig. 19.4).

FIGURE 19.1. Major chronic conditions among persons
older than 65 and 75 years. (From National Center for
Health Statistics, 1984, with permission.)



FIGURE 19.2. Noninstitutional population 65 years of
age and over who have difficulty with instrumental
activities of daily living. (From the National Health
Interview Survey. Supplement on Aging, Division of
Health Interview Statistics. National Center for Health
Statistics, 1984, with permission.)



FIGURE 19.3. Utilization of health services by persons
65 years and older in recent years. (From Aviv JE, Martin
JH, Jones ME, et al. Age-related changes in pharyngeal
and supraglottic sensation. Ann Otol Rhinol Laryngol
1994;103:749, with permission.)



FIGURE 19.4. Projected percentage increase in use of
health services in persons 65 years and older, 19802000
and 19802020. (From Korper SP. Epidemiologic and
demographic characteristics of the aging population. In:
Goldstein JC, Kashima HK, Koopmann CF Jr, eds.
Geriatric otorhinolaryngology. Philadelphia: BC Decker,
1989:19, with permission.)



The data about the epidemiology of otolaryngologic disorders among the elderly are
imprecise; however, Table 19.1 provides a general overview, which reports National
Hospital Discharge Survey results, and Table 19.2 summarizes the recent experience with
diagnostic-related groups.

TABLE 19.1. NATIONAL HOSPITAL DISCHARGE
SURVEY (MDC, 3, >65 YR)



TABLE 19.2. COMPARISON OF DATA SOURCES
FOR TOP FIVE DRGS, AVERAGE LENGTH OF
STAY (MDC 3, >65 YR)



In summation, the 12% of our population over age 65 currently accounts for 33% of the
use of physician time, 25% of medication use, and 40% of hospital admissions. As the
elderly population increases, its impact on society will grow.
HEARING, PRESBYCUSIS, HEARING AIDS, AND ASSISTIVE
DEVICES
An overview of hearing problems is presented here because these topics are covered
more thoroughly in other sections of this book. Surveys have shown that 9.2 million
noninstitutionalized people in the United States over age 65 report having hearing
problems and that 50% of the 1.5 million elderly in nursing homes have impaired
hearing. The ability to understand speech in the midst of normal background noise is a
particularly serious problem for many elderly. The persistent failure to understand what is
being said often leads to frustration, discouragement, passivity, social withdrawal, slowed
mental processes, and depression.
Schuknecht (4) described three definite types of presbycusis on the basis of atrophy of
specific cochlear structures and hypothesized a fourth type that is less well characterized.
These types may occur individually or in various combinations; their features are
summarized in Table 19.3. New hearing aid technology is emerging that promises to
enhance the ability to understand speech within customary background noise. Early forms
of these aids use digital amplification technology and smart filters to improve the
understanding of speech and the perceived sound quality of the aid output. The concept
of compression amplification is being explored in terms of practical usefulness in
hearing aids.

TABLE 19.3. TYPES OF PRESBYCUSIS



The increasing number and the decreasing cost of assistive listening devices are factors in
improving the quality of life for patients with mild presbycusis. Simple amplifying
devices for telephone receivers and small, inexpensive, portable, home
microphone/amplifier/headset devices are available for everyday use. Closed-captioned
television attachments and infrared transmitters are available for home use. Presbycusis is
no longer considered a major factor that causes older patients to withdraw from the world
around them.
TINNITUS
The incidence of tinnitus increases with age. It is present in about 20% of people over age
50 (Table 19.4). Severe tinnitus has been defined as that which plagues me all day
along and has an incidence of about 4% in people over 50. Many studies have reported
an association between tinnitus and psychological diagnoses such as neurosis, neurotic
conversion, borderline personality, depressive range, and anxiety. Dobie et al. (5)
reported finding depression in 24 of 40 patients with severe tinnitus, indicating that
tinnitus may be a factor in causing older people to become depressed.

TABLE 19.4. SUBJECTS EXPERIENCING
TINNITUS OFTEN OR ALWAYS



Confirming causality in these patients is difficult because depressive episodes appear to
precede the tinnitus about as often as not. Preliminary results indicate that nortriptyline, a
tricyclic antidepressant, seems to effectively reduce the severity of tinnitus in these
patients. Severe tinnitus and chronic pain are similar in their effects on people over an
extended time. Medication, counseling, psychological support, and training in various
coping strategies are important components in the therapy of this condition. Tinnitus-
masking devices provide relief in some patients, but their general value in large patient
populations remains controversial.
DYSEQUILIBRIUM AND ATAXIA OF THE ELDERLY
Presbyastasis is the term for the dysequilibrium that results from aging. This condition is
the functional outcome of degenerative changes such as vacuolization of the sensory
epithelium of the semicircular canal ampullae plus fragmentation of the otoconia, along
with morphologic changes in the vestibular nerves, Scarpa ganglion, and the cerebellum.
Affected persons exhibit a progressive decline in their ability to perform eye tracking
tests. Some studies show a decrease in the number of Purkinje cells in the cerebellum.
The ability to maintain normal posture may decrease severely.
With the advancing age, the decline in sensory input along with decreased integrating
ability and weakened muscular function produce balance problems in our patients.
Common disease processes and various medications lead to further functional
degradation. Prevention of falls, treatment, and rehabilitation strategies fall within the
responsibility of the otolaryngologist in many instances.
Konrad et al. (6) pointed out in an excellent review that as we grow older, we lose
balance function through loss of sensory elements, the ability to integrate information and
send motor commands, and because we lose musculoskeletal function. Older patients are
also subject to the common balance disorders of younger patients and require the same
management in addition to placing more emphasis on prevention and rehabilitation. Some
common age-related vestibular disorders are shown in Table 19.5. The effects of aging on
the auditory and vestibular systems are discussed in detail in Chapter 153.

TABLE 19.5. COMMON AGE-RELATED
VESTIBULAR DISORDERS AND TREATMENTS



VOICE DISORDERS IN THE ELDERLY
Vocal quality deteriorates with aging. Several anatomic and functional causes are known,
such as ossification of the laryngeal cartilages, limitation of arytenoid cartilage excursion,
incomplete glottic closure, decreased number of collagen and elastin fibers, and atrophy
of the laryngeal muscles. The fundamental vocal frequency increases in most patients but
may decrease if there is edema or polypoid degeneration of the vocal folds (especially in
smokers). Vocal quality may deteriorate and may be quantifiable by jitter and shimmer
scores or by detection of a senile vocal tremor. Some of these changes are summarized in
Table 19.6. Other changes in vocal quality may result from unsuccessful efforts to
compensate for the effects of aging (Table 19.7).

TABLE 19.6. VOICE EFFECTS OF AGING



TABLE 19.7. UNSUCCESSFUL COMPENSATORY
VOICE USE



OLFACTION AND GUSTATION IN THE ELDERLY
The senses of smell and taste play important roles in the quality of life and the general
state of health of older patients. They give food and beverages their special flavors and
degree of palatability, and they serve to warn of the presence of dangerous volatile agents
such as natural gas, fumes, and smoke. Aging is associated with specific morphologic
changes such as loss of zonal distribution of receptor, sustentacular, and basal cells.
Dilatation of Bowman glands and invagination of the respiratory epithelium into the
lamina propria may occur. The area of the olfactory neuroepithelium may be reduced
with replacement by respiratory epithelium. These processes increase with age and can be
documented using instruments such as the University of Pennsylvania's Smell
Identification Test. Any infectious or inflammatory process can interfere with the access
of odorant molecules to the olfactory epithelium or tastant molecules to the receptor cells
in the taste buds. Degenerative diseases, drugs that decrease cell turnover, radiation
therapy, viral infections, endocrine disorders, neoplasms, and trauma may account for the
decrements in taste and smell observed in the elderly. Age-related changes in ability to
smell and taste have been demonstrated. Unfortunately, the basis for these changes is not
clear. The effects of aging may be a major component, but the interpretation of the
observed functional decrement is clouded by the possibility that other factors are
operating in these patients, such as the cumulative effects of repeated viral infections,
medications, and poor oral hygiene and the onset of various other age-related diseases.
GERIATRIC SINUSITIS AND NASAL SYMPTOMS
Edelstein (7) found that older patients are much more likely to consult physicians for
nasal drainage, postnasal drip, gustatory rhinitis, and decreased olfactory ability. Nasal
resistance was found to be increased as measured by rhinomanometry, but physical
changes in the upper airway could only be found in the nasopharynx.
Upper respiratory infections tend to be underdiagnosed and inappropriately treated in all
age groups. Self-diagnosis and treatment are common and usually involve ineffective
nonprescription medication of various types. These infections account for a large
proportion of the use of the health care system. Common symptoms of sinusitis are
shown in Table 19.8. Predisposing factors include previous nasal fractures, allergic
rhinitis, viral upper respiratory infection, dehydration, foreign bodies, dental abscesses,
nasal polyposis, use of nasal sprays, aspirin, and nasal intubation. Radiographic
assessment and treatment are similar in all age groups. Complications related to
chronicity may be more common in the elderly. The diminished capacity of the immune
system is believed to be a factor in the increased frequency and severity of sinusitis in the
geriatric age group.

TABLE 19.8. COMMON SYMPTOMS OF
SINUSITIS



PRESBYPHAGIA
Swallowing disorders and aspiration are serious problems in a limited segment of the
elderly population. Among the ambulatory elderly, dysphagia is an uncommon diagnosis,
but about 12% of hospitalized patients have swallowing disorders, with an incidence of
about 33% on neurology-neurosurgery services. Almost 50% of residents in some nursing
homes need physical assistance with feeding. The incidence and severity of dysphagia
have not been precisely determined at the present time.
Aspiration is swallowing spillover into the tracheobronchial tree and may produce cough,
intermittent fever, tracheobronchitis, pneumonia, atelectasis, or empyema. Neurologic
disorders are common predisposing factors; these include stroke, epilepsy, drugs, tumors,
and infection. Many forms of neurologic disorders may contribute to dysphagia and
aspiration (8).
It has been shown that sensory discrimination declines in the oral cavity with aging, and
recently Aviv et al. (9) reported that there is a progressive decrease in pharyngeal
sensation with increased age as well. They propose that sensory loss in the hypopharynx
and larynx is a significant factor in some elderly patients who have problems with
aspiration.
Some elderly patients suffer from dysphagia secondary to cricopharyngeal muscle
dysfunction, sometimes termed cricopharyngeal achalasia. These patients have an
unexplained failure of the upper esophageal sphincter to relax completely in a
coordinated manner. Recent reports suggest that most of these patients can be helped by a
surgical procedure (cricopharyngeal myotomy) (10).
Details of evaluating and managing these patients are presented in other relevant
chapters. Many therapeutic options are available to enhance laryngeal function and
swallowing and to prevent the potentially fatal consequences of chronic aspiration.
PERIPHERAL NERVES
Changes in peripheral nerves may be important factors in dysphagia, aspiration, and
deterioration of vocal quality in the elderly. These systems depend on precise
coordination of complex sensory and motor neural systems. We know that several
physiologic and morphologic changes account for age-related dysfunction of neural
systems in the head and neck. These changes include the general tendency to lose
myelinated nerve fibers with increasing age, pathologic changes in Schwann cells, an
increase in the cross-sectional area of nerves (caused by an increase in the endoneurial
extracellular space), and vascular changes (such as endothelial proliferation and media
fibrosis). The changes observed in the superior and recurrent laryngeal nerves are
summarized in Fig. 19.5. Altogether, these changes in peripheral nerves appear to parallel
the observed deterioration of deglutition, respiration, and vocalization in the elderly (11).

FIGURE 19.5. Summary of aging-related changes in
recurrent laryngeal nerve and superior laryngeal nerve in
animal models. (From Malmgren LT. Aging-related
changes in peripheral nerves in the head and neck. In:
Goldstein JC, Kashima HK, Koopmann CF Jr, eds.
Geriatric otorhinolaryngology. Philadelphia: BC Decker,
1989:138, with permission.)



GERIATRIC IMMUNOLOGY
With increasing age, a person's immune system becomes less effective in its primary
function of protecting against infections and neoplastic disease. Invading microbes and
neoplastic cells trigger reactive responses designed to confine and destroy foreign
substances. T and B lymphocytes have specific surface receptors that are stimulated by
contact with immunogens to proliferate, thus increasing the number of cells available to
respond defensively. Clones of the responding cells differentiate into effector cells, with
B cells being transformed into antibody-secreting plasma cells and T lymphocytes into
lymphokine-secreting or cytotoxic effectors. Some of the lymphokines produced by T
cells promote growth and maturation of B cells, others recruit and activate mononuclear
and polynuclear phagocytes, and others activate the T cells themselves. The T-
lymphocyte activation sequence is summarized in Table 19.9.

TABLE 19.9. EARLY EVENTS IN T
LYMPHOCYTE ACTIVATION



Lymphocytes are not as effective in older people for the following reasons:
1. The function of helper and cytotoxic T-cell activity declines.
2. The general response to antigens and immunogens decreases (possibly because of
structural changes in the long-lived memory cells/T lymphocytes in the
system).
3. The thymus gland involutes.
4. Older T and B cells seem to produce a weaker response intrinsically.
5. The quality of the overall response is decreased (less IgG and fewer antibodies are
produced).
BENIGN AND NONSQUAMOUS NEOPLASMS
The distribution and biologic behavior of benign and nonsquamous malignant neoplasms
of the head and neck are different in elderly patients. Aggressive clinical behavior is
common, and delays in seeking medical attention occur more frequently. In addition,
psychosocial and ethical issues arise that are unique to older patients. The most common
nonsquamous tumors are those involving the thyroid and salivary glands. Fibroosseous
tumors and hemangiomas are rarely found in elderly patients. Anaplastic or
undifferentiated thyroid cancer is much more common in patients over 65 years, and
medullary carcinoma and thyroid lymphomas are seen more often. Well-differentiated
thyroid carcinoma behaves much more aggressively, and the recurrence rate for papillary
carcinoma is higher in geriatric patients. Substernal goiter is primarily a disease of the
middle-aged and elderly.
Salivary gland malignancies are seen more frequently in patients over 50 years of age.
High-grade mucoepidermoid carcinoma is more common in the elderly, whereas low-
grade mucoepidermoid cancer is seen more frequently in young patients. Older age
generally is a poor prognostic factor for patients with parotid malignancy.
Non-Hodgkin's lymphoma of the upper aerodigestive tract is a disease of the middle aged
and elderly. Special considerations in managing malignancy in older patients include the
following:
1. Anxiety about medical costs;
2. Lack of knowledge or concern about symptoms;
3. Social isolation;
4. Lack of personal physician;
5. Fatalistic attitudes about disease and treatment outcome.
SQUAMOUS CELL CARCINOMA
Approximately 70,000 new cases of head and neck cancer are diagnosed each year, with
the average patient age being 59 years. About 80% of these tumors are squamous cell
carcinomas, and the overall 5-year survival rate is approximately 67% for patients with
localized disease and 30% for patients with regional metastasis. The major theory of
carcinogenesis involves the probable combination of a genetic predisposition, an inciting
carcinogen, and a defective immune surveillance system. Humans are exposed to families
of carcinogens and to specific known carcinogens. Detailed information concerning the
diagnosis and management of specific head and neck neoplasms is found in other
chapters dealing with each anatomic site.
FACIAL PLASTIC SURGERY IN THE ELDERLY
The increasing trend for older patients to feel vigorous and healthy has been paralleled by
an increase in the demand for surgical procedures that enhance their appearance.
Growing numbers of older patients want to look as good as they feel. The number of
cosmetic surgical procedures has doubled in the past decade, with patients over 50 years
old accounting for much of this growth.
Rhinoplasty is performed much more frequently in elderly patients than it was in earlier
years. Many of these patients have consulted surgeons when the effects of aging have
compounded preexisting functional or cosmetic deformities. With aging, the nasal tip
often becomes ptotic and a nasal hump becomes more noticeable. Surgical goals must be
more conservative in this age group, with less tissue excision and with nasal pyramid
rasping rather than chisel or saw excision. Radical aesthetic changes are usually avoided
because most of these patients wish to be restored rather than remade. Healing takes
longer, and redraping of the skin occurs slowly, especially in the glabellar region. Tip
rotation often enhances nasal breathing. (For more information on rhinoplasty, see
Chapter 173, Chapter 174, Chapter 175, Chapter 176, Chapter 177 and Chapter 178.)
Blepharoplasty is performed frequently, often to correct the tired and listless appearance
of the eyes. The redundant skin and herniated orbital fat is excised, without changing the
natural eye contour or expression. (For more information on blepharoplasty, see Chapter
179.)
Rhytidectomy is the primary facial plastic surgical procedure concentrated in the aging
population. Patients who undergo this surgery must be in sufficiently good health to
ensure adequate healing. (For more information on rhytidectomy, see Chapter 180 and
Chapter 181.)
SKIN CHANGES OF AGING
Possible causes for the aging of skin include genetic and environmental factors. Some
form of genetic regulation of the number of skin cell replications can occur. With aging,
the level of mitotic activity decreases, leading to evidence of atrophy. Cross-linking of
fibrous proteins and nucleic acids is an important phenomenon in aging. Cross-linking of
nuclear DNA strands may result in genetic abnormalities and plays a role in the induction
of malignancy. Free radicals may enhance the formation of epoxides, which are potent
cross-linking agents. Ionizing radiation and solar ultraviolet radiation trigger free radical
chain reactions. Patients of all ages should be urged to use sunscreens.
Important age-related skin changes include the following:
1. Decreased moisture content and cellular cohesion in the stratum corneum layer;
2. Effacement of the rete ridges of the epidermis;
3. Heterogeneity of keratinocyte nuclei;
4. Decreased population of melanocytes and Langerhans' cells (an important part of
the local immune system);
5. Thinning of the dermis;
6. Decreased elastic tissue;
7. Loss of oxytalan fibers (causes skin laxity);
8. Haphazard collagen deposition;
9. Fewer small vessels, fibroblasts, macrophages, mast cells, Pacini's corpuscles,
Meissner's corpuscles, and sweat glands;
10. Smaller sebaceous glands.
These changes slow wound healing and reduce inflammatory response. Common benign
skin lesions in the elderly are seborrheic keratosis, skin tags, cherry hemangioma,
chondrodermatitis nodularis chronica helices, angular cheilitis, xanthelasma,
keratoacanthoma, and wrinkles.
Skin malignancy is covered in detail in Chapter 103 and Chapter 104; specific
dermatologic lesions are covered in detail in Chapter 187.
AIRWAY MANAGEMENT
Management of the geriatric airway may be complicated by associated general disease,
specific pulmonary pathology, or medications. A major issue in managing respiratory
problems in the elderly is the need for prolonged intubation. This is commonly defined as
intubation for longer than 2 weeks, which is associated with a much higher rate of
complications resulting from presence of the endotracheal tube.
The risk of tracheal stenosis is estimated to be about 5% to 10% after 10 days of
intubation and about 14% in patients intubated for longer than 10 days. Endotracheal
tubes may injure the airway by material biotoxicity, cuff pressure, or tube wall pressure.
The prevention of tube-induced injury is a criti-cal consideration. Laryngotracheal
pathology includes diffuse edema, mucosal erosion over the arytenoid vocal process,
posterior glottic horseshoe lesion, granulation tissue, vocal cord paralysis, and cricoid
cartilage abscess. Nasal ulceration or sinusitis may result from prolonged intubation.
FACIAL FRACTURES
The capacity for self-regeneration and healing in bone declines with advancing age.
There may be associated endocrinopathy with disturbed calcium metabolism, suboptimal
nutritional status, and a reduced blood supply. Much of the blood supply to facial bones
depends on vessels in the subperiosteal plexus and adjacent soft tissues; therefore,
periosteal elevation should be kept at a minimum during the management of geriatric
facial fractures.
With advancing age, the upper and lower alveolar ridges undergo resorption. This occurs
even if the teeth are still present, but in the absence of teeth, the resorption is often
marked, with loss of more than 50% of total mandibular height. Resorption markedly
weakens the strength of the mandible and predisposes it to fracture with the impact of
much less force. A major problem in trauma management, resorption makes it more
difficult to achieve solid bone healing in good position (because of the markedly reduced
contact area between bone fragments).
As a general policy, the management of facial fractures in the elderly focuses on
techniques that are minimally invasive, require less dissection, and introduce less
hardware into the wound. Healing requires about 50% longer than in young adults.
Nutritional management (both support and supplementation) is critical in older patients.
As Fee (13) emphasized, age alone should not be used as a determinant for surgery.
Sound medical judgment and individual patient evaluation should guide our treatment
decisions.

HIGHLIGHTS
The process of aging is the sum of many phenomena: disease,
environmental insult, injuries, nutrition, and genetic
programming.
The etiology of the aging process is not fully understood.
Theories explaining aging include finite limits on the number of
cell replications, the somatic mutation theory, the error theory,
and the program theory.
The United States is experiencing unparalleled growth in the
number of older people.
There are 9.2 million noninstitutionalized older people and 1.5
million hearing-impaired elderly in nursing homes in the United
States.
Ataxia of the elderly (presbyastasis) causes many damaging
falls annually among the elderly, results in numerous femoral
fractures, and contributes to significant morbidity, mortality,
and high health care costs.
Swallowing disorders and aspiration (presbyphagia) are serious
problems in the elderly and may cause cough, fever,
pneumonia, atelectasis, empyema, or death.
The immune system becomes less effective in the elderly in
terms of protecting against infections and neoplastic disease.
Malignant neoplasms are especially problematic in the elderly
because of more aggressive clinical behavior and delays in
seeking medical attention.
Facial plastic surgery to counteract the skin changes of aging
(blepharoplasty and rhytidectomy) has become much more
popular during the past decade.
Management of the geriatric airway may be complicated by
associated general disease, specific pulmonary pathology, or
medications. Prolonged intubation (longer than 2 weeks) is a
major issue in managing respiratory problems in the elderly.
CHAPTER REFERENCES
1. Bailey BJ. Perspectives on health care for the elderly. In: Goldstein JC, Kashima HK, Koopmann
CF Jr, eds. Geriatric otorhinolaryngology. Philadelphia: BC Decker, 1989:189192.
2. Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res
1961;24:585.
3. Korper SP. Epidemiologic and demographic characteristics of the aging population. In: Goldstein
JC, Kashima HK, Koopmann CF Jr, eds. Geriatric otorhinolaryngology. Philadelphia: BC Decker,
1989:1928.
4. Schuknecht HF. Pathology of presbycusis. In: Goldstein JC, Kashima HK, Koopmann CF Jr, eds.
Geriatric otorhinolaryngology. Philadelphia: BC Decker, 1989:4044.
5. Dobie RA, Katon WJ, Sullivan M, et al. Tinnitus, depression, and aging. In: Goldstein JC,
Kashima HK, Koopmann CF Jr, eds. Geriatric otorhinolaryngology. Philadelphia: BC Decker,
1989:4548.
6. Konrad HR, Girardi M, Helfert R. Balance and aging. Laryngoscope 1999;109:14541460.
7. Edelstein DR. Aging of the normal nose in adults. Laryngoscope 1996;106[Suppl]:125.
8. Blitzer A. Swallowing disorders and aspiration in the elderly. In: Goldstein JC, Kashima HK,
Koopmann CF Jr, eds. Geriatric otorhinolaryngology. Philadelphia: BC Decker, 1989:124133.
9. Aviv JE, Martin JH, Jones ME, et al. Age-related changes in pharyngeal and supraglottic
sensation. Ann Otol Rhinol Laryngol 1994;103:749752.
10. St. Guily J, Zhang KX, Perie S, et al. Improvement of dysphagia following cricopharyngeal
myotomy in a group of elderly patients. Ann Otol Rhinol Laryngol 1995;104:603609.
11. Malmgren LT. Aging-related changes in peripheral nerves in the head and neck. In: Goldstein JC,
Kashima HK, Koopmann CF Jr, eds. Geriatric otorhinolaryngology. Philadelphia: BC Decker,
1989:138143.
12. Miller RA. Age-related immune deficiency. In: Goldstein JC, Kashima HK, Koopmann CF Jr, eds.
Geriatric otorhinolaryngology. Philadelphia: BC Decker, 1989:106111.
13. Fee WE Jr. Surgery in the aging population. Arch Otolaryngol Head Neck Surg 1999;125:1406
1407.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

20 HEADACHE AND FACIAL PAIN
Head & Neck SurgeryOtolaryngology
20




HEADACHE AND FACIAL PAIN
ALAN G. FINKEL
J. DOUGLAS MANN
THOMAS F. LUNDEEN

A.G. Finkel: University Headache Clinic, and Department of Neurology, University of North Carolina,
Chapel Hill, North Carolina.
J.D. Mann: Department of Neurology, University of North Carolina, Chapel Hill, North Carolina.
T.F. Lundeen: Carolina Oral and Facial Pain Center, Durham, North Carolina.


Intracranial Pain-Sensitive Structures and Patterns of Referred Pain
Patterns of Referral for Jaws and Teeth
History
Physical Examination
Clinical Syndromes
Tension-type Headache
Migraine Headache
Cluster Headache
Trigeminal Neuralgia
Glossopharyngeal Neuralgia
Posttraumatic Neuralgia
Postherpetic Neuralgia
Atypical Facial Pain
Temporomandibular Disorders
Brain Tumor
Pseudotumor Cerebri (Benign Intracranial Hypertension)
Subdural Hematoma
Subarachnoid Hemorrhage
Temporal Arteritis
Hypertension
Posttraumatic Headache
Low Intracranial Pressure Headache
Infection of the Nervous System
Chronic Daily Headache
Sinus Headache
Complications
Emergencies
Status Migrainosus
Trigeminal Neuralgia
Temporal Arteritis
Pseudotumor Cerebri
Chapter References
Pain is the major reason patients seek medical care, and the head and face are the most
common locations for pain. Of all the patients who consult a physician for head pain,
90% suffer from vascular headache of the migraine or cluster type, tension headache, or a
mixture of the two. The other 10% suffer from conditions leading to inflammation,
traction, or dilatation of pain-sensitive structures of the head and neck.
INTRACRANIAL PAIN-SENSITIVE STRUCTURES AND PATTERNS
OF REFERRED PAIN
Although the brain is not pain sensitive, the supporting structures surrounding it are
heavily invested with nociceptive nerve fibers (Table 20.1). Pain is produced whenever
these structures are subjected to traction/distortion, inflammation, or in the case of
migraine abnormal activation of trigeminovascular structures. For structures inside the
skull, pain is referred to areas of the scalp, face, jaw, and neck. When the pathology is in
the anterior or middle cranial fossa, pain is referred to the scalp or face anterior to the
coronal suture. With lesions involving posterior fossa structures, pain is referred to the
back half of the head and upper neck. Pain arising from the sphenoid sinus or the sella is
often referred to the cranial vertex. Pain coming from discrete lesions involving the
incisura may produce anterior and posterior head pain simultaneously, although this
pattern of pain is much more commonly seen with generalized intracranial disease such
as meningitis or subarachnoid hemorrhage.

TABLE 20.1. DIAGNOSIS GENERAL
CONSIDERATIONS FOR HEADACHE AND
FACIAL PAIN ASSESSMENT



PATTERNS OF REFERRAL FOR JAWS AND TEETH
The temporomandibular joint (TMJ) and the muscles of mastication can be a source of
pain that radiates to the head and ear. The TMJ is innervated by the auriculotemporal
nerve as it passes behind the condyle and then upward in front of the ear. The
intraarticular disk (meniscus) and the articulating surfaces of the articular eminence and
condyle are covered with dense connective tissue (rather than the hyaline cartilage found
in most joints) that is avascular and not innervated. Thus, most of the TMJ cannot
produce pain. Pain originating in the TMJ must occur as a result of inflammation of the
synovial tissues of the joint and the surrounding capsule. Erosion of the articular
coverings results in exposure and damage to the subjacent bone and produces bone pain
in degenerative joint disease and other arthralgias.
The muscles of mastication are a more important source of pain than the TMJ because
muscle pain is more intense and more common than the TMJ pain. Pain can be reported
as a diffuse temporal headache or as ipsilateral ear pain. In chronic myofascial pain, the
muscles of mastication become tender to palpation and have characteristic tender spots
that can be detected by palpation. Pericranial tenderness is found in migraineurs and
myofascial pain patients and thus is not an exclusive characteristic of myofascial pain.
Tooth pain is poorly localized and can be confused with disorders occurring outside the
mouth. It can present as diffuse facial or ear pain. The pulp-dentin complex of teeth
responds to most stimuli by producing pain. The mechanism of transduction of these
mechanical stimuli to pain is not well characterized but is most likely due to fluid
movement in the dentinal tubules. Obturation of the dentinal tubules with dental resins or
by sclerosis eliminates tooth sensitivity. The tooth pulp has little recuperative ability
because of the limited blood supply through the tooth roots. Thus, infection or
inflammation of the tooth pulp often results in pulpal necrosis. Pulpal death results in
localization of the pain to the offending tooth.
HISTORY
A thorough history, as outlined in Table 20.2, is the key to efficient assessment of
headache patients. Particular attention should be paid to the following considerations:

TABLE 20.2. DIAGNOSIS DOCUMENTING
HEADACHE HISTORY



The characteristics of the pain the very first time the patient experienced it should
be asked about: rate of onset, rate of offset, intensity, quality, location, duration,
and response to medications.
The quality of the pain can suggest its origin: pressurelike (viscus- or chamber-
derived pain), sharp and shooting (neuritic), throbbing (vascular), or burning and
aching (muscular).
Most primary headache diagnosis can be made on the basis of temporal profile.
The most common diagnostic errors are based on misinterpretation of duration.
For example, cluster headache rarely lasts more than 4 hours that any headache
longer than that is something other than cluster. Two-week migraine is also
improbable. Data on chronic daily sinus pain do not exist to validate this
cephalgia.
Exacerbating and relieving factors need to be documented. Medications, body
movement, stress, foods, menses, or anything the patient reports as influencing
the pain may be important clues to headache type.
Associated nonpainful symptoms should be asked about, such as visual or somatic
aura (suggesting migraine) or lacrimation and ipsilateral nasal congestion
(suggesting cluster headache). The presence of photophobia in greater than 90%
of migraineurs suggests its power in the diagnosis of migraine, whereas emesis
occurs in only 10% to 30% of patients with migraine.
The presence of trigger points needs to be sought, particularly for neuritic or
muscular pain or provocation by facial or jaw movement.
PHYSICAL EXAMINATION
The physical examination is guided by the history and pain description. Routine
examination for headache should include assessment of head, neck, and jaw range of
movement; extraocular movements, pupillary reaction to light and accommodation;
ocular fundus; mouth; tongue; dentition; and lymphatics, in addition to the usual ear,
nose, and throat structures. Physical findings that are sometimes missed but that may give
a clue to diagnosis include the following:
Limited or asymmetric jaw opening with noises or tenderness over the TMJ;
tenderness of the masseter or temporalis musculature (assessed by joint palpation
during mouth opening and by the three-finger test);
Any abnormality of vision including visual field defects, extraocular movements,
funduscopy (increased intracranial pressure or mass lesion);
Enlarged, nodular, cordlike, apulsatile, or tender temporal scalp arteries (temporal
arteritis);
Trapezius or posterior cervical trigger points that, when palpated, radiate pain into
the cranium or face (myofascial pain);
Occipital notch tenderness to palpation or light percussion with spread of the pain
to the posterior scalp and temporal or sometimes retroorbital areas ipsilaterally
(occipital neuralgia);
Small white scars from herpetic lesions involving the tympanic membrane,
external ear, or portions of V1 hidden in the hair;
Asymmetric skull percussion tenderness over the lateral scalp, suggesting an
underlying subdural process on the side of tenderness.
Some combinations of history and physical findings that can alert the physician to a very
high likelihood of underlying organic disease of serious nature are listed in Table 20.3.
Table 20.4 gives a differential diagnosis for early-morning headache.

TABLE 20.3. DIAGNOSIS CLINICAL
FEATURES SUGGESTING SERIOUS CAUSE FOR
HEADACHE



TABLE 20.4. DIAGNOSIS DIFFERENTIAL
DIAGNOSIS OF EARLY MORNING HEADACHE



CLINICAL SYNDROMES
The publication of the International Headache Society's (IHS) classification and
diagnostic criteria for headache disorders, cranial neuralgias, and facial pain in 1988
opened up a new era for the understanding of clinical headache diagnosis. In the
following sections, important conditions are described, along with treatment
recommendations when appropriate. See Table 20.5 and Table 20.6 for topics covered.

TABLE 20.5. DIAGNOSIS DIFFERENTIAL
DIAGNOSIS OF HEADACHE



TABLE 20.6. TREATMENT EPISODIC
TENSION-TYPE HEADACHE



Tension-type Headache
Because of the ambiguity of the term tension headache (physical tension, psychic
tension), the terminology has been changed to tension-type headache. Episodic tension-
type headache is the most common head pain syndrome. It is characterized by a gradual
onset of bilateral, nonthrobbing, aching pain over the frontal and temporal regions, often
spreading to involve the occipital, posterior cervical, and trapezius musculature. The pain
often worsens as the day goes on. Associated symptoms such as nausea and vomiting are
rare, and patients usually can continue activities of daily living during the headache. The
headaches are not seasonal and do not wake the patient from sleep. Tension-type
headache is commonly associated with or precipitated by physical or psychological
stress. The stressful event and the headache are closely linked in time, and the sufferer
can readily make an association between the two events. Patients who acknowledge a
significant role of stress in the etiology of their headaches often benefit from biofeedback
and stress management regimens. Adults rarely seek medical care for occasional tension
headaches. Chronic daily headache occurs in about 1% to 2% of the general population.
Chronic tension-type headache is responsible in about 25% of daily headache sufferers.
The patients seeking medical care for chronic, persistent, or recurrent headaches most
often present with transformed migraine (see next section). The most commonly
encountered problem in this group is analgesic rebound headache and depression.
Combination therapy, including limited nonsteroidal antiinflammatory drugs (NSAIDs)
and antidepressants, is the most effective treatment.
Many organic causes for headache produce symptoms very similar to those of tension
headache. Hence, the features listed in Table 20.3 and Table 20.4 become important in
the workup of patients with what seem to be tension headaches. Other causes should be
suspected when one or more of the following statements apply:
There is a crescendo pattern to the headaches.
Sharp or clearly throbbing pain is a part of the pattern.
Nausea is prominent.
The headaches occur mainly in the morning hours.
Medications are progressively less effective.
The causes of tension-type headache are poorly understood despite its well-described
symptom profile. There is no firm evidence for the role of muscle contraction or spasm in
these patients, though the IHS does include pericranial musculature (neck, face, and
head) in the categorization of this headache. Recent experimental evidence implicates
dopaminergic and endorphin/enkephalin in tension-type headache, as opposed to the
serotonergic theories of migraine. Muscle relaxants, massage, and biofeedback can be
very effective in some patients with the typical clinical features, whereas other patients
require antiinflammatory medications and/or antidepressants. Open-label comparison
studies have demonstrated the effectiveness of the selective serotonin reuptake inhibitors
in chronic daily headache when compared with amitriptyline. Therapy must be tailored to
the specific needs of each patient. For example, a patient with chronic tension-type
headache, sleep disturbance, and depressed affect might respond best to an antidepressant
medication, whereas a patient with hypertrophic masseter muscles and worn teeth might
respond best to an anxiolytic. Suggested treatments are listed in Table 20.6.
Migraine Headache
Recent advances in our understanding of migraine headache have produced a tremendous
improvement in the success of management of this disabling condition. Important
epidemiologic studies have shown migraine to occur in 17% of adult females and 6% of
adult males. It has also been shown to be an expensive condition for society based on
estimates of decreased efficiency and lost work. The recognition of its importance has
been mirrored by the creation of new classes of medication for both symptomatic and
prophylactic therapy.
Migraine headaches consist of recurrent attacks of moderate to severe throbbing head
pain of sudden onset and limited duration, usually in a hemicranial distribution, with
associated complaints reflecting autonomic overactivity (Table 20.7). Photophobia and
phonophobia are common (1). There is a strong female preponderance, and hormonal
fluctuations during the menstrual cycle and pregnancy play a major role in the triggering
of pain in many patients. Onset is usually in the second or third decade, although young
children can have migraines (or migraine equivalents such as recurrent abdominal pain,
vertigo, or syncope). Onset in the 40s and 50s is rare. Many variations exist, including
basilar artery migraine with loss of vision or syncope, migraine aura without the
headache, and transformation of migraine in later life to unusual head pain syndromes
such as ice pick pain or more generalized nonhemicranial headaches. General features
of migraine are summarized in Table 20.8.

TABLE 20.7. TREATMENT INTERNATIONAL
HEADACHE SOCIETY CRITERIA FOR
MIGRAINE



TABLE 20.8. DIAGNOSIS MIGRAINE WITH
AND WITHOUT AURA



The financial and societal impact of migraine has been recognized, and migraine-
associated disability is recognized and well studied. The availability of new medications,
in part, is a function of the pharmacoeconomic importance of migraine and its effective
treatment.
Research strongly suggests that central nervous system events trigger intracranial vessel
changes through the trigeminovascular system and peripheral and central sites. Both
animal and human studies have confirmed the importance of serotonin receptor subtypes
in the central nervous system mechanisms and intracranial blood vessel change. Newly
available treatments, such as sumatriptan, are agonists at the 5-hydroxytryptamineld
neurovascular junction receptor. Also important in the production of migraine are the
neuropeptides calcitonin gene-related peptide, neurokinin A, and substance P, all known
proinflammatory moieties. Research in treatment is now largely directed toward
manipulation of these entities in hopes of reducing vasoconstrictive complications of
ergots and serotonin agonists, that is, increases in blood pressure and coronary/cerebral
vascular events. Although there are many possible triggers, there seems to be a final
common event that produces a sterile inflammation around the intracranial blood vessels
and results in the typical migraine headache (Table 20.9).

TABLE 20.9. PRECIPITATING FACTORS IN
MIGRAINE



Migraine can be managed by aborting attacks at their onset, controlling pain once the
headache has fully evolved, and reducing the frequency of migraine attacks. All abortive
methods are most effective if started as soon as the premonitory or warning signs are
noted. When abortive treatment fails, attempts should be made to reduce the pain
intensity and limit the associated symptoms of migraine, especially nausea and vomiting.
Preventive therapy should be initiated for patients suffering two or more migraine attacks
per month. Prophylaxis is especially important because migraine can cause considerable
personal, financial, and social losses.
To review, the three major treatment strategies used in most patients with migraine are as
follows:
Aborting further development of pain by starting drugs shortly after the first
warning symptoms or at the earliest onset of pain if there are no warning
symptoms (2) (Table 20.10)

TABLE 20.10. TREATMENT
PATIENT-CONTROLLED
ABORTIVE SYMPTOMATIC
THERAPY FOR MIGRAINE



Treating the pain if abortive therapy fails (Table 20.11);

TABLE 20.11. TREATMENT
ACUTE THERAPY FOR MIGRAINE



Preventing the headache by limiting life events that predispose to headache;
promoting a healthy lifestyle in terms of sleep, diet, exercise, and stress reduction;
and/or giving prophylactic medication to prevent the biochemical events leading
to migraine (Table 20.12).

TABLE 20.12. TREATMENT
MEDICATIONS USEFUL IN THE
PREVENTION OF MIGRAINE



Migraine prophylaxis is a fundamental part of migraine management. Principles for the
use of prophylactic medication include the following:
Recent advances in abortive/symptomatic medications have changed prophylaxis
in one fundamental way (many patients can now effectively and quickly treat
several migraines a month as they occur without high degrees of migraine-
associated disability). Nevertheless, use of preventive medication is indicated in
patients with more than two migraines per month (2).
Start medications at the low end of the dosage range and increase over several
weeks to therapeutic effect or side effects.
Start one medication at a time.
Allow at least 3 weeks on each medication before deciding on efficacy.
Do not combine calcium channel blockers with -blockers.
Medications for acute pain and abortive therapy can be mixed with those for
prophylaxis, although the use of sumatriptan and concurrent ergots is
contraindicated (3).
Cluster Headache
Cluster headache is characterized by the explosive onset of severe unilateral periorbital or
retroorbital pain (Table 20.13). In contrast to migraine, cluster pain is relatively constant
and has boring or burning qualities rather than throbbing or pulsating features typical of
migraine. Cluster also lacks nausea and photophobia common in migraine. Other
distinctive features include associated autonomic symptoms on the ipsilateral side such as
nasal stuffiness, lacrimation, and conjunctival injection. An individual cluster headache is
short, lasting 15 to 180 minutes, in contrast to the 1 to 3 days of migraine. This is the only
headache syndrome with a male preponderance. Cluster is also associated with alcohol
use and intolerance. Treatment is primarily prophylactic during the weeks or months of
the cluster (Table 20.14). Once an effective treatment has been found for a given patient,
therapy is usually continued for 6 to 8 weeks and then gradually discontinued. If the
headaches return during the taper, the drug is reinstituted at the full dosage (4).

TABLE 20.13. DIAGNOSIS CLINICAL
FEATURES OF CLUSTER HEADACHE



TABLE 20.14. TREATMENT MEDICATIONS
FOR PREVENTION OF CLUSTER HEADACHE



Acute therapies are listed in Table 20.15. Each one is tried for three or more headaches
before deciding on efficacy. Oxygen therapy seems particularly effective in younger
patients with cluster occurring mainly at night. Recent promising medications include
some calcium channel blockers, valproic acid, and the H
2
blockers (5).

TABLE 20.15. TREATMENT ACUTE
THERAPY FOR CLUSTER HEADACHE



Table 20.16 outlines the major topics to be covered in the next sections.

TABLE 20.16. TREATMENT NEURALGIAS
AND OTHER CAUSES OF FACIAL PAIN



Trigeminal Neuralgia
Trigeminal neuralgia is a syndrome of repetitive brief attacks of severe, sharp, jabbing, or
lancinating pain occurring in the distribution of one or more divisions of the fifth cranial
nerve. Although individual attacks of pain are very brief, lasting seconds at most, they
may occur many times in rapid succession and many times a day, resulting in significant
functional impairment. Spontaneous remissions lasting many months or even years are
not uncommon. The typical syndrome occurs in patients over 50 and runs a progressive
or fluctuating course over many years. The pain is localized most often in the second or
third divisions of the nerve, with triggers commonly found at the corner of the mouth or
lateral aspect of the nose. Triggers are small areas on the face that precipitate an attack
when touched. Triggers may also arise in deeper structures such as the sinuses, oral
mucosa, periodontal ligaments, fascia, and muscles. Patients are often very protective of
the face, fearing stimulation of the trigger by light touch, heat, cold, or wind. Washing the
face, shaving, and applying makeup are done with extreme care, if at all. Chewing or
stimulating the buccal mucosa or gums may produce paroxysms of pain.
The syndrome is not associated with facial numbness, weakness, loss of corneal reflex,
change in taste or smell, or other cranial nerve impairment. The presence of those
findings should suggest another diagnosis, such as brain or meningeal tumor,
nasopharyngeal pathology, chronic basal meningitis, Raeder syndrome, or internal carotid
aneurysm. Onset in the second to fourth decades of ticlike pain, with or without focal
findings, suggests multiple sclerosis, congenital anomaly at the base of the skull,
infection, or vascular malformation.
Diagnostic workup of patients with the symptoms of tic in any age group should include
magnetic resonance imaging (MRI) of the head with and without contrast. A lumbar
puncture should be performed in patients in whom the MRI does not clearly demonstrate
a cause and when there are additional signs and symptoms to the classic syndrome.
Cerebrospinal fluid (CSF) should be sent for cryptococcal antigen, Venereal Disease
Research Laboratory test (VDRL), and cytology, in addition to the routine cells, protein,
glucose, tuberculosis, and bacterial cultures (6).
Medical treatment includes, in order of preference, trials of carbamazepine, gabapentin,
baclofen, phenytoin, sodium valproate, or chlorphenesin (Table 20.17). Each drug should
be tried for at least 2 weeks. Carbamazepine and valproate are started at half the
recommended maintenance dosage and increased gradually over 2 to 3 weeks.
Gabapentin can be rapidly titrated to up to 3,600 mg/day by adding 900 mg (300 mg
three times a day) every 2 weeks. Phenytoin can be orally loaded at a rate of 500 mg
twice a day for 2 days, then 100 mg three times a day. Combinations of two drugs may be
tried, particularly if the use of one drug at full dosage results in partial relief of the pain.
Adjunctive therapy consists of tricyclic antidepressants and NSAIDs. Opiates are
effective in only a few patients. Surgical treatment is considered when medications
cannot control the pain (7). Percutaneous rhizotomy is now replacing more complicated
open procedures.

TABLE 20.17. TREATMENT MEDICATIONS
FOR TRIGEMINAL, GLOSSOPHARYNGEAL,
AND POSTTRAUMATIC NEURALGIA



Glossopharyngeal Neuralgia
The glossopharyngeal nerve is also subject to development of neuritic-type pain similar
in its temporal profile, pain characteristics, and intensity to that of trigeminal neuralgia.
The sharp lancinating pain is unilateral and is located variably in the posterior pharynx,
soft palate, base of the tongue, ear, mastoid, or side of the head. There may be associated
hiccuping, nausea, vertigo, tinnitus, a sense of fullness in the ear, hearing loss, or
dysgeusia. The pattern of attacks is very unpredictable. Triggers may be located in the
throat. Workup and treatment are the same as for trigeminal neuralgia (8) (Table 20.17).
Posttraumatic Neuralgia
Head trauma is occasionally associated with the development of neuroma and neuritic
pain. Sites of head injury leading to this problem most often include the lateral parietal
and occipital regions. Predisposing factors include poor wound closure, local infection,
retained foreign materials, skull fracture, extensive subcutaneous swelling or hematoma,
diabetes mellitus, and coexisting peripheral neuropathy elsewhere in the body. A similar
syndrome can follow local infections of the scalp without trauma, particularly herpetic.
The time between injury and the onset of pain is variable, but 2 to 6 months is a common
interval. The initial pains may be mild and nonneuritic in type, evolving into a more
typical pattern over several months. Although trigger areas may be evident on
examination, the pain is often spontaneous and poorly correlated with patient activities.
Treatment includes the same medications used for trigeminal neuralgia. Recurrent
infiltration of trigger areas with a local anesthetic such as bupivacaine can be surprisingly
effective, providing extended relief over many months after a series of three or four
injections. Surgical removal of a well-defined trigger is attempted in some patients when
there is limited response to the above treatments.
Injuries to the trigeminal nerve occur as the result of facial trauma and surgery. Probably
the most common injury is to the mandibular branch of the trigeminal nerve as a result of
third molar extraction. The reported incidence of trigeminal nerve injuries is 3% to 5%
for third molar removal and 90% to 100% for mandibular osteotomies. Most injuries
produce anesthesia; pain is a rare consequence. The mandibular nerve is most commonly
injured by compression of the nerve in the mandibular canal, either by direct pressure of
the root tip or local swelling and edema after tooth removal. Most cases present as
persistent anesthesia or paresthesia after the local anesthetic has worn off. Complete
recovery occurs in more than 90% of the cases; fewer than 10% have permanent
anesthesia. Recovery is usually complete in 3 to 4 months. Anesthesia persisting after this
period has a poor prognosis. Pain is rare, but when it occurs, it is present as a burning or
aching dysesthesia that is very resistant to treatment.
The diagnosis is made by a history of facial trauma or surgery, an onset of symptoms
closely related in time to the trauma, and the clinical characteristics of the pain. Painful
posttraumatic neuralgias occurring in the trigeminal nerve were described by Gregg as
having hyperalgesia, hyperpathia, anesthesia dolorosa, and sympathetically mediated
pain. Hyperalgesia is characterized by rapidly responding pain to light sensory stimuli
that are normally not perceived as painful. Hyperpathia is pain that results from repeated
stimulation of the skin. Anesthesia dolorosa is pain that is felt in an area of skin that is
reported to be numb and has a markedly decreased sensitivity to strong sensory stimuli.
Sympathetically mediated pain is aggravated by increased sympathetic tone, cold, and
emotional stimuli. Antiepileptic drugs such as carbamazepine, phenytoin, or baclofen are
the most useful for shooting shocklike pain, and tricyclic antidepressants such as
amitriptyline are used for burning, aching, dysesthetic pain (Table 20.17). When
medication fails, surgical repair can be attempted. Microsurgical repair produces 50% to
60% pain reduction in patients with hyperalgesia and hyperpathia and 15% to 20% pain
reduction with anesthesia dolorosa and sympathetically maintained pain.
Postherpetic Neuralgia
Herpetic skin eruption is a common disorder caused by the varicella-zoster virus. The
virus infects the trigeminal nerve in childhood as chickenpox. The virus remains dormant
in sensory nerve ganglia for decades and can be reactivated by trauma or stress or during
periods of compromised immune function. The reactivated virus is transported distally in
the axon and produces small crusting pustules on the skin. Trigeminal herpes zoster is the
second most common location after the thoracic region. The acute infection produces a
combination of burning, itching, and lancinating pain. Secondary infections of the skin
worsen the pain. Muscle splinting often occurs, and secondary muscle pain can result.
Immunocompromised patients should be treated with antiviral medications such as
acyclovir, NSAIDs, or opioids for pain during the acute phase. Other patients may be
treated with a 10-day course of oral prednisone, 40 mg/day, tapering after 5 days.
Pain persisting after 2 months can be labeled as postherpetic neuralgia. Opioid and
NSAIDs often are of little use in this stage. Anticonvulsants are the most useful for pain
management and may be combined with tricyclic antidepressants or baclofen to control
the lancinating and shooting pains. Prognosis for a good response to the medication or
spontaneous recovery worsens with advancing age.
Atypical Facial Pain
Atypical facial pain is described as a chronic burning or aching pain without focal
findings or any discernible etiology. It is a diagnosis of exclusion. Characteristically the
pain is bilateral and changes locations frequently over weeks to months. The pain is not
triggered and is not shocklike; thus it is easily distinguishable from trigeminal neuralgia.
Pain intensity fluctuates slowly over time, and pain is rarely entirely absent. The pain is
typically located in the face and rarely spreads to the cranium, which distinguishes it
from tension headache. Palpable muscular spasm involving the pterygoids or masseters is
uncommon. Women are much more commonly affected than men and are usually 30 to
50 years old. Significant psychiatric findings are found in 60% to 70% of the patients;
depression, somatization, and adjustment disorders are the most common. Psychiatric
assessment is recommended.
Atypical facial pain can be managed with antidepressants. Patients are started on a low
dose (25 mg) of amitriptyline at bedtime and titrated up until sleep and pain are
improved. These patients are at risk for iatrogenic problems due to multiple invasive
evaluations and excessive medication.
Temporomandibular Disorders
These disorders are covered more thoroughly in Chapter 49, and are not expanded upon
here.
Brain Tumor
Thirty percent of patients with primary or metastatic brain tumor have headache at the
time of diagnosis, and 15% have headache as the presenting complaint. The headache is
often intermittent, dull, aching, lateralized, and relatively mild in the beginning,
responding to nonnarcotic analgesics. Early-morning headache is present in less than
10% of patients but is a very useful diagnostic clue when present, particularly when there
is vomiting without significant premonitory nausea. A characteristic feature is the
crescendo quality of the headache, with greater intensity and frequency of pain along
with less response to analgesics over time. Worsening of the headache with a change in
body position, coughing, or straining is common. Focal neurologic findings and
complaints may not be evident despite significant head pain complaints.
Pseudotumor Cerebri (Benign Intracranial Hypertension)
Pseudotumor cerebri is defined by the combination of papilledema, an otherwise normal
neurologic examination (with the rare exception of a sixth nerve palsy), a normal
computed tomography (CT) showing no intracranial mass or hydrocephalus, CSF
pressure above 200 mm H
2
O, and normal CSF chemistries and cultures. It shares many of
the same symptoms with brain tumor, including intermittent headache of variable often
gradually increasing intensity. Additional features include the following:
Predisposing mastoid or inner ear infection;
Menstrual irregularity or other endocrine abnormality;
Recent weight gain of more than 10% of baseline weight over 6 months;
Exposure to steroids (especially during their withdrawal), vitamin A, tetracycline,
or nalidixic acid;
Retroorbital or vertex localization of the headache, particularly with empty sella
syndrome;
Visual obscurations or dimming of vision occurring for seconds to minutes with
or without intensification of the headache;
Recurrent unilateral or bilateral tinnitus;
Constriction of visual fields in cases lasting longer than several months.
Treatment includes weight reduction, a low-salt diet, medications directed at reducing
CSF production (acetazolamide and furosemide, used separately or together), and in
chronic cases with visual field loss not responding to diet and medications, CSF
diversionary procedures (lumboperitoneal or ventricular shunting, optic nerve sheath
incision).
Subdural Hematoma
A fluctuating level of consciousness with complaints of moderate to severe continuous
headache in association with trauma is common in patients with subdural collections of
blood. Additional features include lateralization of the headache to the side of the
hematoma, ipsilateral skull percussion tenderness, and signs of head trauma, including
Battle's sign (bruising over the mastoid) and blood behind the tympanic membrane. In the
case of chronic subdural hematomas, the head trauma may be remote from the time of
patient presentation or may not even be remembered.
Subarachnoid Hemorrhage
Sudden onset of severe generalized headache (the worst headache of my life) occurs in
all patients presenting with acute subarachnoid hemorrhage secondary to ruptured
aneurysm or vascular malformation. A few patients present with surprisingly focal head
pain early in the process. Localization of the pain to the face is uncommon, although
retroorbital and supraorbital pain are often reported. Nausea, vomiting, and stiff neck are
very common. Lethargy and confusion are more variable. A third nerve lesion with
pupillary involvement can help localize an aneurysm to the ipsilateral posterior
communicating artery. Other focal neurologic signs may be present or not, depending on
the combination of arterial blood extravasating into the brain and secondary vasospasm.
Development of a stiff neck followed by back pain as the blood finds its way down to the
spinal subarachnoid space can be helpful symptoms in suspecting the diagnosis. If brain
imaging does not show blood or mass effect but the diagnosis is still suspected, a
diagnostic lumbar puncture should be performed (24).
Temporal Arteritis
Ninety-five percent of patients with temporal arteritis (giant cell arteritis) are over 60
years of age. They present with complaints of daily moderate to severe headache, scalp
sensitivity, generalized fatigue, and feelings of being unwell in nonspecific ways.
Unilateral head pain is the rule, but the pain can be bilateral or in the occipital region
exclusively, reflecting the highly regional distribution of the disease. Brief episodes of
sharp shooting head pain are sometimes superimposed on a baseline of continuous dull
aching pain. Carotid artery pain, jaw pain, or jaw claudication has been reported.
Enlarged, thickened, or tender scalp arteries are found on palpation of the scalp in about
half the cases. This condition shares the same pathology as polymyalgia rheumatica, and
many patients have overlapping symptoms of extremity pain. The sedimentation rate is
elevated in all but the rarest of cases as the only consistently abnormal laboratory test.
Although scalp artery biopsy in the region of the pain can confirm the diagnosis, it may
be negative in documented cases because of the spotty nature of the disease. Patients
respond with a dramatic reduction in head pain within days of starting high-dose (60 mg)
daily prednisone. Lack of a definite clinical response to prednisone within several weeks
makes the diagnosis much less secure without a positive biopsy. The sedimentation rate
usually falls within weeks of starting steroids. Prednisone can be tapered to an every-
other-day maintenance schedule over a period of weeks after the headache and
sedimentation rate have corrected. The disease lasts 1 to 2 years, during which
maintenance steroids are continued to prevent visual loss as the major complication
(estimated to be as high as 30% in untreated cases).
Hypertension
There is very poor correlation between headache and chronic elevations in blood pressure
so that control of blood pressure cannot be reliably gauged on the basis of headache
symptoms. Head pain becomes a more consistent complaint in patients with diastolic
pressures above 115 mm Hg. The pain in this group may be throbbing, associated with
nausea, and poorly responsive to analgesic medications. Acute headache associated with
rapid rises in blood pressure may be an indication of pheochromocytoma, renal artery
stenosis, or hyperadrenalism.
Posttraumatic Headache
Headache after head trauma becomes a problem most often when it occurs in association
with the other manifestations of posttraumatic syndrome: depression, somatic
preoccupation, and sleep disturbance. The headache is typically frontal and occipital,
often present at some level day and night, and poorly responsive to medications. Patients
often express concern that the physician will miss the diagnosis of a life-threatening
condition, and doctor shopping is common. A fascinating negative correlation exists
between severity of head trauma and complications of headache. Unlike patients with
subdural hematomas, skull percussion tenderness is absent, and the examination is
normal. Treatment consists of reassurance and a course of antidepressants. The tricyclics,
when given as a single pre-bedtime dose, improve both sleep and mood in addition to
modulating pain. Selective serotonin reuptake inhibitors may improve lethargy and
behavioral sequelae. Daily use of over-the-counter analgesics should be minimized to
avoid the development and perpetuation of chronic daily headache (see below).
Neuritic pain with a trigger and typical radiating pattern can develop after head injury,
usually within 3 to 6 months. The mechanism is believed to be neuroma formation within
the damaged tissue. The pain is typically sharp and lancinating with radiation in a
peripheral nerve distribution. Pain may be spontaneous and/or associated with a discrete
trigger zone. More chronic and long-duration pain is believed to be related to perturbation
of intracranial structures and axonal shear injury.
Medications used for treatment of neuritic components are the same as for trigeminal
neuralgia (Table 20.17). Injections with a local anesthetic can be very effective if trigger
points can be located. Surgical exploration with extirpation of the neuroma or scar is
sometimes attempted. Although chronic daily head pain may be more treatment resistant,
medications should be directed toward the phenomenology of the headache; that is, if the
headache has features of migraine, tension type, or cluster, treat with medications
normally used for those conditions. TMJ pain may be a sequela of whiplash injury.
Low Intracranial Pressure Headache
Low intracranial pressure headache is well recognized and occurs most often as a
complication of lumbar puncture. The headache appears or worsens when the patient is
upright and improves or disappears completely within minutes of lying down. The
incidence after lumbar puncture increases with the size of the needle used and is about
15% when an 18-gauge needle is used. The pain is temporal, occipital, or vertex; tends to
be steady; and is often described as pulling in quality. Nausea is common, and episodes
of transient sixth or third nerve paresis are reported.
Spontaneous recovery within days is the rule. Bedrest and fluids reduce the symptoms but
have not been shown to speed recovery. Limited evidence supports a trial of intravenous
(i.v.) caffeine sodium benzoate (500 mg in 1,000 mL of 5% dextrose in water over 60
minutes). Autologous blood patching in the epidural space at the site of the puncture is
definitive treatment in almost all cases that do not spontaneously resolve. Rarely, low-
pressure headache occurs spontaneously (i.e., without prior lumbar puncture). There may
be an associated history of remote or relatively minor head or back trauma or of
connective tissue disease. Spontaneous resolution is the rule, although identification of
the site of CSF leak and surgical repair is sometimes required. Myelogram is the
diagnostic test of choice. CSF leakage into the sinuses after head trauma is well
described. Chronic low-pressure headache needs referral to a neurologist.
Infection of the Nervous System
Infection producing headache is usually not a diagnostic problem when there is
associated stiff neck and fever. However, nonspecific headache without the other findings
can be part of the picture in epidural abscess; fungal, tuberculous, or luetic meningitis;
central nervous system acquired immunodeficiency syndrome (AIDS); and meningeal
sarcoidosis. The diagnosis depends on the clinician's index of suspicion and patient
willingness to have a lumbar puncture with culture and antigen studies after CT or MRI
studies of the head have ruled out an intracranial mass. Recommended studies include
CSF VDRL, cryptococcal antigen, and angiotensin-converting enzyme levels in addition
to the routine studies, including bacterial and tuberculosis cultures.
AIDS patients may have chronic headache in the absence of meningitis or cerebral
abscess. The headache is nonspecific and is most often tension in type. Questions of how
often CSF studies should be repeated arise frequently. After a baseline CSF study,
including a VDRL and cryptococcal antigen, reexamination of the CSF should be limited
to patients with significant changes in their headache pattern or intensity. Serum titers are
not very helpful for developing toxoplasmosis, because the titers tend to be high in a
large percentage of the population to begin with. Changes in serum cryptococcal antigen
can herald activation of central nervous system infection and should be checked every 3
months in the setting of persistent headache, even if the headache is not changing
significantly (9).
Chronic Daily Headache
The use of pain relievers more than three times a week is often associated with refractory
headache. Discontinuing daily use of symptomatic medications results in an improvement
of headache over a period of weeks to months. This syndrome is associated with the use
of common over-the-counter and prescription medications containing aspirin,
acetaminophen, other NSAIDs, codeine, barbiturates, hydrocodone, oxycodone, or
propoxyphene for the treatment of headache. Most patients presenting with daily
headache have a history of migraine without daily headache in the past. The concept of
transformed migraine, where analgesic use, physical or emotional trauma, or natural
progression leads to intractable daily headache, is now well established in the headache
literature.
The head pain is present daily and is typically bilateral, frontal, occipital, nonthrobbing,
and moderately severe. It can be associated with nausea at its peak and responds partially
to the medication that creates the problem. The history reveals an increasing need for
medication and few periods of complete relief. Often the chronic daily headache is
descriptively distinct from the headache for which the medication was originally taken.
The original headache may still occur, mixed in with the chronic daily head pain.
Questions directed toward different headache types quickly sort out the problem in most
cases.
Patients with chronic daily headaches have a history of episodic migraine and tension
headache that preceded the chronic daily headache. Current physiologic concepts of
headache recognize that tension and migraine headaches are probably physiologically
related, and a central hypothesis is gaining support. This follows observations that
centrally mediated events result in local changes in the vasculature and musculature that
consequently produce the local pains clinically recognized as migraine or tension
headache. Over time, episodic headaches in some patients gradually become chronic
daily headaches. Headache-prone patients (those with a strong family history of
headaches and who have had multiple headaches in childhood, adolescence, or early
adulthood) are at risk for the development of chronic daily headaches. Excessive use or
abuse of pain-relieving headache medications, alcoholism, and depression are strongly
associated with the development of chronic daily headache. Withdrawal symptoms
during the early phases of treatment can be prominent. They occur most commonly in the
first 4 days but last up to 3 weeks in some cases. Withdrawal symptoms consist of
nervousness, restlessness, increased headaches, nausea, vomiting, insomnia, diarrhea, and
tremor. Hospitalization may be necessary to manage the patient during the withdrawal
phase and to provide the necessary control of medications not possible on an outpatient
basis.
The treatment must include the following:
Explanation of the syndrome to the patient;
Complete cessation of use of the offending medication for at least 2 months after
a maximum taper period of 10 days;
Nonsubstitution of other agents that could perpetuate the pain (e.g., propoxyphene
for butalbital, aspirin for acetaminophen plus codeine);
Use of a daily antidepressant at gradually increasing doses to effect or to the
recommended antidepressant dosage;
Use of biofeedback, muscle relaxants, transcutaneous electrical nerve stimulation,
or physical therapy for treatment of the pain;
Referral to a neurologist for inpatient management using dihydroergotamine in
refractory cases.
Medical therapies for the primary headache, particularly when it is migraine, are often
ineffective during treatment of drug-induced chronic daily headache and may need to be
temporarily discontinued. However, discontinuation of daily use of analgesics results in
an increase in the effectiveness of prophylactic medications if they are continued.
Sinus Headache
The authors of the IHS Manual for Headache Diagnosis make the following comment:
Other conditions which may cause headache such as nasal passage abnormality due to
septal deflection, hypertrophic turbinate and atrophic sinus membranes are not
sufficiently validated as causes of headache. Chronic sinusitis is not validated as a cause
of headache unless relapsing into an acute phase. Migraine and tension type headache are
often confused with true sinus headache because of similarity in location. Disease in the
sinuses may present with frontal pain or pain radiating behind the eyes or to the vertex
(frontal sinus), over the antral area or temporal area (maxillary), between and behind the
eyes or to the temporal area (ethmoid), or between or behind the eyes or to the vertex
(sphenoid).
COMPLICATIONS
Complications in headache assessment and management are summarized in Table 20.18.

TABLE 20.18. COMPLICATIONS HEADACHE
ASSESSMENT AND MANAGEMENT



Often the biggest barrier to successful headache management is not the diagnosis or
choice of medication but issues surrounding patient behavior and expectations. All
patients bring their own beliefs, needs, and expectations to the clinical encounter. Many
complications and treatment failures in the headache population can be traced to the
erroneous assumption that the patient has the same beliefs, needs, and expectations as the
doctor.
For example, a 16-year-old boy was referred for evaluation of head and face pain. The
referral contained a warning about drug-seeking behaviors and inappropriate use of
emergency departments. The young man was having migraine headaches. After the
physician got to know him and gained his trust, the patient revealed that he was very
fearful that there might be no end to a headache attack once it started. His fear of ever-
increasing pain was the motivator for him to seek immediate treatment for every attack.
His trips to the emergency department stopped abruptly when his fears were properly
addressed. He was given a prescription for sumatriptin and instructed in how to use it to
abort attacks. Furthermore, he was told that even if nothing was done about an attack,
there was an upper limit to the pain and that headaches can run their course without
causing permanent damage. Even though he got only partial pain relief with the
sumatriptin, he had enough control of his pain that he could let go of his fears. The
emergency department visits stopped. He was also started on sertraline, and after a
month, his headache frequency began to drop dramatically. This illustrates how doctors'
and patients' beliefs can differ radically. Until this patient's needs and beliefs were
understood, he received inappropriate treatment and a damaging label.
EMERGENCIES
Emergencies presenting as a complaint of headache are listed in Table 20.19.

TABLE 20.19. EMERGENCIES COMPLAINT
OF HEADACHE



Status Migrainosus
Migraine can become so persistent that patients experience a severe continuous headache
over many days. This represents a medical emergency, because most of these patients
cannot function, become progressively dehydrated secondary to recurrent vomiting, and
often have complications associated with overmedication. They require hospitalization
for dehydration and pain management.
Patients are given i.v. 5% dextrose in quarter-normal saline at about 90 mL/h for the first
24 hours. Because nausea and vomiting are major problems, i.v. prochlorperazine is
given in doses of 15 mg every 3 to 6 hours as needed. This also provides some sedation
and may contribute directly to alleviation of the headache. Dihydroergotamine can be
used in doses of 0.5 mg i.v. to start with and then 1.0 mg every 8 hours up to 3 days.
Common experience indicates that headaches are rapidly alleviated within 1 to 2 days
with this regimen. Use of small doses of intramuscular or i.v. morphine can be effective
in reducing pain intensity, but opiates can intensify the nausea and vomiting and
significantly extend the time to recovery. If the decision is made to use opiates, a time-
contingent regimen is recommended, with either i.v. or intramuscular morphine given
every 4 to 6 hours for a period of 24 hours, with reassessment of the effectiveness of
these agents at the end of that time.
Use of -blockers, tricyclic antidepressants, and benzodiazepines is contraindicated in the
acute situation. The role of calcium channel blockers has yet to be defined in this setting.
There is some support for the combined use of phenobarbital in tapering doses along with
a short course of i.v. prednisolone, also in a tapering regimen, beginning with 40 mg i.v.
and tapering rapidly over 4 days (10).
Trigeminal Neuralgia
Patients occasionally suffer intense activation of their disease, resulting in the need for
acute pain management on an emergent basis. The medication of choice for this condition
is carbamazepine or baclofen, neither of which can be given intravenously. Oral
gabapentin has shown some promise in acute neuralgiform pain of this type and can be
titrated upward rapidly, starting with 300 mg three times a day. Intravenous or oral
steroids may be used in a pulse fashion to induce pain relief. Tricyclic antidepressants
can be started at low doses simultaneously with the anticonvulsant regimen and may
yield improved sleep and pain control. Opiate analgesics are often ineffective at moderate
doses but can provide some relief in acute situations. Temporary nerve block is
sometimes effective and may be needed in cases not responding rapidly to oral or
intravenous medications.
Temporal Arteritis
Patients presenting with a history of chronic daily headache who are over age 60 and
have an elevated sedimentation rate (above 35 mm/h) need to be considered for temporal
arteritis. The risk of permanent visual loss in at least one eye is about 30% and can be
prevented by the rapid administration of steroids. Establishing a diagnosis sometimes
depends on the response to steroids. Hence, when the clinical condition is suspected but
cannot be fully proved, administration of 60 mg of oral prednisone is justified. This
should be continued on a daily basis for at least 2 weeks before slow tapering is
considered. Repeat sedimentation rate and assessment of the patient's response to steroids
will establish the correctness of the diagnosis. Patients with temporal arteritis almost
invariably respond with a rapid reduction in head pain within 72 hours of starting
prednisone. The sedimentation rate will begin to drop within 7 to 10 days. Temporal
artery or occipital artery biopsy remains positive in the face of oral steroids for up to 2
weeks. Hence, there is no need to postpone administration of steroids until a temporal
artery biopsy is obtained.
Pseudotumor Cerebri
Patients with pseudotumor cerebri experiencing visual obstructions (dimming) are at high
risk for developing blindness secondary to venous retinal infarction. The visual loss can
occur acutely and is presumed to be associated with episodic elevations in intracranial
pressure, leading to obstruction of retinal venous outflow. Patients with papilledema but
without visual obscurations can be treated with oral medications to reduce CSF
formation, such as acetazolamide or furosemide. The effectiveness of oral agents is
usually evident within several days. Patients with visual obstructions should undergo
lumbar puncture after imaging studies (CT or MRI of the head) to rule out intracranial
mass or blocked CSF pathways. Reduction in CSF pressure can be achieved acutely
through lumbar puncture and may be safely repeated as often as necessary. Continued
visual obscurations in the face of repeated lumbar puncture and oral medications may
require consideration of CSF diversionary procedures such as lumboperitoneal shunting
or optic nerve sheath fenestration.

HIGHLIGHTS
Intracranial pain-sensitive structures include the major arteries
at the base of the brain; the major venous sinuses; and cranial
nerves V, VII, IX, and X. Pain is experienced when these
structures undergo traction, dilatation, or inflammation.
Patients seeking medical care for headache will be suffering
from vascular and/or tension headache as the primary problem
9 times out of 10.
Symptoms suggesting that a serious structural disease is
producing headache are usually present when the patient is first
seen. A careful history should include questions directed toward
onset, duration, and frequency of pain; associated symptoms;
and precipitating and relieving factors, including medications,
family history, and stress.
Head pain brought on primarily by coughing or exer-tion; early-
morning headache; crescendo headache; and headache with
fever, stiff neck, focal neurologic deficits, papilledema, and
altered mental status all suggest underlying life-threatening
conditions.
Migraine is a very common vascular headache disorder
characterized by a rapid onset of throbbing head pain that lasts
hours to days, often associated with a visual aura, photophobia,
phonophobia, nausea, vomiting, and diarrhea. Associated
features include a female preponderance, onset in the second or
third decade of life, and a strong family history.
Effective abortive treatment for migraine is best achieved with
sumatriptan, ergotamine, isometheptene, or NSAIDs.
Medications effective in migraine prevention include daily
ergotamines, -blockers, tricyclic antidepressants, calcium
channel blockers, or NSAIDs.
Temporomandibular disorders have multiple etiologies,
including combinations of internal derangements of the
articular disk, degenerative joint disease, and myofascial pain
leading to lateralized head and face pain. Treatment is similar to
that for tension headaches and includes NSAIDs, biofeedback,
trigger point injections, and physical therapy.
Neuritic head pain, such as trigeminal neuralgia, is
characterized by repetitive, short-duration, and sharp shooting
pains, often with one or more trigger zones on the scalp or face
or in the mouth. The pain may respond to anticonvulsant
medications, baclofen, tricyclic antidepressants, or
neurosurgery.
Chronic daily head pain, with features of either tension or
vascular headache, can result from daily use of over-the-counter
analgesics, prescription NSAIDs, narcotics, ergotamines,
barbiturates, or benzodiazepines. Treatment includes patient
education, withdrawal of the offending medication,
administration of tricyclic antidepressants during the
withdrawal phase, and physician-regulated reinstitution of
analgesics as needed after withdrawal.
Medical emergencies involving headache as a major symptom
include subarachnoid hemorrhage, subdural hema-toma,
temporal arteritis, pseudotumor cerebri, brain tumor, brain
abscess, and hydrocephalus.
CHAPTER REFERENCES
1. Capobianco DJ, Cheshire WP, Campbell JK. An overview of the diagnosis and pharmacologic
treatment of migraine. Mayo Clin Proc 1996;71:10551066.
2. Maizels M, Scott B, Cohen, et al. Intranasal lidocaine for treatment of migraine: a randomized,
double-blind, controlled trial. JAMA 1996;276:319321.
3. Weitzel KW, Thomas ML, Small RE, et al. Migraine: a comprehensive review of new treatment
options. Pharmacotherapy 1999;19:957.
4. Gaist D. Use and overuse of sumatriptan. Pharmacoepidemiological studies based on prescription
register and interview data. Cephalalgia 1999;19:735.
5. Mathew N. Cluster headache. Neurology 1992;42[Suppl 2]:2231.
6. Jackson EM, Bussard GM, Hoard MA, et al. Trigeminal neuralgia: a diagnostic challenge. Am J
Emerg Med 1999;17:597.
7. Rizvi SS, Goyal RN, Calder HB. Hearing preservation in microvascular decompression for
trigeminal neuralgia. Laryngoscope 1999;109:591.
8. McLaughlin MR, Jannetta PJ, Clyde BL, et al. Microvascular decompression of cranial nerves:
lessons learned after 4400 operations. J Neurosurg 1999;90:1.
9. Lipton RB, Feraru ER, Weis G, et al. Headache in HIV-1-related disorders. Headache
1991;31:518522.
10. Lake AE, Saper JR, Madden SF, et al. Comprehensive inpatient treatment for intractable migraine:
a prospective long-term outcome study. Headache 1993;33:5562.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

21 MANIFESTATIONS OF THE ACQUIRED IMMUNODEFICIENCY SYNDROME
Head & Neck SurgeryOtolaryngology
21




MANIFESTATIONS OF THE ACQUIRED
IMMUNODEFICIENCY SYNDROME
THOMAS A. TAMI
KELVIN C. LEE

T.A. Tami: ENT Department, University of Cincinnati Medical Center, Cincinnati, Ohio.
K.C. Lee: ENT Department, University of CaliforniaSan Francisco, San Francisco, California.


The Acquired Immunodeficiency Syndrome Epidemic
Human Immunodeficiency Virus and Host Response
Clinical Manifestations
Dermatologic
Otologic
Nose and Paranasal Sinuses
Oral Cavity and Pharynx
Larynx
Neck
Occupational Risks and Prevention
Chapter References
THE ACQUIRED IMMUNODEFICIENCY SYNDROME EPIDEMIC
In the second decade of our encounter with the ravages of the human immunodeficiency
virus (HIV), we have seen distinct changes in the natural history and management of the
acquired immunodeficiency syndrome (AIDS). HIV-infected patients have been living
longer as we have become better at treating the consequences of their immunodeficiency
and its many manifestations. Continued research has also resulted in new treatments for
the primary viral infection itself. This chapter presents a history of the AIDS epidemic
and reviews its otolaryngologic manifestations.
AIDS first received public attention in 1981 when several authors described clusters of
cases of Kaposi's sarcoma (KS) and Pneumocystis carinii pneumonia in otherwise
healthy homosexual men in New York and California. As the reporting of these cases
accelerated, AIDS was rapidly discovered to be a problem of epidemic proportions.
Although early attention focused on the homosexual population, it became quickly
apparent that intravenous drug abusers (IVDAs), hemophiliacs, and blood transfusion
recipients were also particularly prone to the development of this syndrome. This
immune disorder was characterized by a progressive deficiency of helper T lymphocytes;
in 1983 and again in 1984, a virus was isolated that appeared to be responsible for the
development of AIDS. This retrovirus has been designated the human immunodeficiency
virus, and as a result of its isolation and characterization, serum antibody titers to HIV
were quickly identified. Tests that identify these antibody markers (ELISA, Western blot)
continue to serve as major serologic markers of HIV infection.
During the early and mid-1980s, the HIV epidemic progressed almost completely
unabated. Although homosexual men continued to account for most patients with AIDS,
IVDAs, hemophiliacs, transfusion recipients, and eventually heterosexuals all became
increasingly more affected by the epidemic. The initial geographic centers of infection in
the United States were the major coastal metropolitan areas such as San Francisco and
New York; however, AIDS soon began appearing in less populated regions. Currently,
few geographic areas in the United States are untouched by the epidemic.
As the epidemic has gained momentum, heterosexual spread has become a greater
concern and is receiving wider attention. As of November 1999, the Centers for Disease
Control and Prevention (CDC) had reported 612,078 cases of AIDS among persons of all
ages in the United States. The World Health Organization has estimated that more than
42 million adults and nearly 1 million children were infected with the AIDS virus
worldwide. Each day 16,000 more people become infected with the virus (1).
Approximately 40% of HIV-infected adults are women. Women now play a prominent
role in the epidemic, and vertical transmission from infected mother to child has
produced a growing population of HIV-infected children. Although these numbers are
small when compared with the adult epidemic, AIDS remains the number one cause of
childhood immunodeficiency and ranks among the 10 leading causes of death in children
in the United States.
Based on data obtained from the San Francisco City Clinic Cohort Study, approximately
50% of HIV-infected patients will develop AIDS within 10 years of their initial infection.
Given this long incubation period, as well as the continuing trend toward longer survival
with medical interventions, the far-reaching impact of AIDS will clearly continue well
into the next century.
HUMAN IMMUNODEFICIENCY VIRUS AND HOST RESPONSE
Immediately after the identification of HIV, researchers quickly defined its structure,
mechanisms, and host interactions. This enabled the development of strategies for
potential drugs and vaccines and facilitated the institution of clinical trials to evaluate
agents possibly effective in combating HIV. To better appreciate HIV and the special
problems presented by this unusual virus, a basic understanding of retroviruses and their
modes of interaction with host cells is critical.
The HIV virus particle has an outer lipid bilayer with distinct glycoproteins (designated
gp120 and gp41) protruding from its surface that allow it to bind with appropriate host
cells. Within this capsule is the viral core, consisting of structural proteins, two identical
strands of RNA, and the important enzyme reverse transcriptase. The cell cycle of HIV is
illustrated in Fig. 21.1. Upon contacting a compatible host cell, viral surface
glycoproteins bind to host cell membrane receptors. These host receptors (CD4 receptors)
are present in high concentrations on helper T lymphocytes and account for the
predilection of HIV for these cells. Several other cell types also have low concentrations
of CD4 receptors (e.g., monocytes, macrophages, central nervous system [CNS] dendritic
cells), and they can also be infected.

FIGURE 21.1. Human immunodeficiency virus (HIV)
life cycle. Step 1: Free HIV particles bind to surface CD4
receptors of helper T lymphocyte. Step 2: Viral core
RNA is injected into host cell. Step 3: After the
conversion of viral RNA into DNA using viral enzyme
reverse transcriptase, the DNA migrates to the host cell
nucleus to be incorporated into the host genome
(provirus). Step 4: After a variable latent period, the
provirus begins to direct the synthesis of new HIV particles Step 5: Free HIV particles
are released after cell lysis.



After initial binding, the viral and host cell membranes fuse, and the viral core is injected
into the host. The viral enzyme reverse transcriptase immediately begins to synthesize
DNA from the viral RNA template. This DNA migrates to the host cell nucleus, becomes
incorporated into the host cell DNA, and thus permanently infects the host cell with HIV.
This incorporated HIV DNA, referred to as a provirus, is now an integral part of the host
cell genome; as the host cell multiplies, the HIV provirus also multiplies. Some of the
early drugs used to treat HIV infection (zidovudine [AZT], dideoxyinosine) acted by
inhibiting the action of reverse transcriptase, thereby interfering with the synthesis of
DNA.
The provirus remains latent until activated by unknown cellular or environmental
influences, and the second part of its life cycle begins. Using host cell enzymes, the
provirus directs the synthesis of new HIV particles, which attach to the inner surface of
the host cell membrane, causing cell lysis and freeing HIV particles to reinfect other cells
with CD4 surface receptors.
A new class of antiretroviral drugs, the protease inhibitors, acts at this stage in the HIV
life cycle. These agents (saquinavir, ritonavir) interfere with the activity of enzymes
needed to assemble new virus particles. Tremendous excitement has surrounded the use
of these new agents, both as monotherapy and in combinations. Although these drugs
have shown a dramatic ability to decrease HIV viral load to often undetectable levels and
have in many cases produced dramatic clinical improvement in HIV-infected patients,
researchers remain wary of premature enthusiasm lest their long-term effectiveness
becomes muted as a result of viral resistance. Nevertheless, there is renewed hope that
HIV infection may soon be transformed from a fatal illness to a chronic disease (2).
Immunodeficiency resulting from HIV infection is due to the loss of helper T
lymphocytes. Because these cells play an important role in the cellular-mediated immune
system, HIV-infected patients are susceptible to opportunistic infections from viral,
bacterial, protozoal, and mycobacterial sources and are prone to develop unusual
malignancies. As the population of helper T lymphocytes gradually diminishes, the
morbidity and mortality of this disease increase. Because of this striking association, the
absolute helper T-lymphocyte count (CD4 count), a widely available test, is commonly
used as a quantitative marker of HIV disease stage. The normal CD4 count is usually well
above 1,000; however, HIV-infected patients display a steadily decreasing count. Counts
below 200 are associated with a level of immunosuppression that allows the clinical
manifestations classically used to define AIDS. Clinicians frequently use the CD4 count
to determine the need for various therapeutic and prophylactic regimens.
The CDC has established specific criteria to define and stage AIDS. In 1982, AIDS was
defined by the presence of one of several defining opportunistic infections (e.g., P.
carinii pneumonia, toxoplasmosis, Cryptococcus) or malignancies (e.g., KS, non-
Hodgkin's lymphoma [NHL]) in patients with no other defined cause for
immunosuppression. In 1987, this definition was broadened to include other
noninfectious noncancerous HIV-associated conditions, such as AIDS dementia complex
and HIV wasting syndrome. The use of these more inclusive clinical criteria to define
AIDS still excluded many patients with severely diminished immune function. In 1993,
the CDC further modified its definition of AIDS to include all HIV-infected patients with
CD4 counts of fewer than 200 (3).
Although only 50% of seropositive patients develop AIDS within the 10 years after the
initial HIV infection, the median survival after the diagnosis of AIDS is much shorter. In
1987, the median survival was 24 months. This has increased to 53 months in 1993 and
will hopefully be extended even further with continued use of antiretroviral agents,
prophylactic medical protocols to prevent or delay opportunistic infections, and the recent
introduction of the new class of protease inhibitors.
Most HIV-infected patients mount a substantial antibody response; nevertheless, this
response does not confer lasting protection against the effects of the virus. Antibodies are
produced primarily against the glycoprotein components of the external envelope, regions
that are highly variable and subject to a high rate of genetic mutation. This has been a
major obstacle to the development of effective vaccines against HIV. The other major
reason that HIV vaccines may be ineffective in preventing infections is that vaccines are
aimed primarily at neutralizing free virus particles. Evidence suggests that infection with
HIV can occur by cell-to-cell transmission of HIV, thus bypassing the effects of
neutralizing antibodies. Despite these obstacles, investigators continue to work toward
developing vaccines either to prevent the transmission of HIV or to augment the immune
response in patients who are already infected.
CLINICAL MANIFESTATIONS
Patients infected with HIV can present with many different problems in the head and
neck, including frequent acute infections with the usual human pathogens, opportunistic
infections, neurologic complaints, and certain specific neoplastic processes. Throughout
the natural progression of HIV disease, each new phase brings about certain types of
manifestations. During the early stages of infection, as the CD4 count is gradually
decreasing, patients experience more frequent viral and bacterial infections and
candidiasis. As the CD4 count drops below 200 and AIDS fully develops, infections with
unusual opportunistic organisms and the occurrence of HIV-associated neoplasms begin
to predominate. Because almost 50% of all patients with HIV-related problems present
with pathologic conditions in the head and neck, otolaryngologists must be ready to
recognize and manage these patients (4).
Dermatologic
The incidence of fungal and viral infections of the skin, such as candidiasis, tinea
versicolor, and molluscum contagiosum, increases as the CD4 count decreases. The
clinical response to medical therapy also decreases, often necessitating prolonged
treatment with more potent medications. Molluscum contagiosum is extremely common
in patients with symptomatic HIV disease. These pearly umbilicated papules usually
measure from 2 to 5 mm and often have a predilection for the eyelids. They can
occasionally grow very large, forming giant molluscum bodies and often requiring
excision or cryosurgery. Cutaneous histoplasmosis and Cryptococcus lesions have also
been reported in AIDS patients but are extremely uncommon. Cutaneous Cryptococcus in
AIDS patients almost always indicates systemic infection and should trigger a search for
pulmonary or CNS cryptococcosis.
During the later stages of HIV disease, up to 83% of patients develop extensive
seborrheic dermatitis, often involving the face and scalp. Although this process can
present in a variety of ways, the inflammatory and hyperkeratotic forms predominate.
Other hyperproliferative dermatoses have also been associated with AIDS; however, the
pathophysiologic skin changes that promote these conditions are unclear.
Bacillary angiomatosis is an uncommon infectious condition found primarily in
immunosuppressed patients, particularly those with symptomatic HIV disease. Although
this condition can affect multiple organ systems, the skin seems particularly susceptible.
Because the causative organism, a bacterium closely related to cat-scratch disease, is
extremely difficult to culture, diagnosis is usually established histopathologically. The
skin lesions may appear as subcutaneous nodules or as friable vascular papules. Therapy
with oral erythromycin is usually very effective; however, if left untreated, bacillary
angiomatosis can be fatal.
Herpes zoster infections with typical dermatomal distribution or the Ramsay Hunt
syndrome have been reported in up to 16% of AIDS patients. Symptoms tend to be more
severe in these patients and the response to medical therapy less predictable. Permanent
cranial nerve palsies are occasionally unavoidable, and disseminated disease (primary
chickenpox) has also been reported. Lesions can occasionally persist for up to 10 months.
Although treatment for herpes zoster includes acyclovir and analgesics, the use of
systemic steroids, especially with facial nerve involvement, remains controversial in
these immunosuppressed patients.
Idiopathic multiple sarcoma of the skin, better known as KS, is the most common
neoplasm associated with AIDS. Originally a rare disease in the United States, it has
become one of the most common findings in patients with AIDS. Not all AIDS patients
are equally affected by KS. Although 43% of homosexual or bisexual AIDS patients have
KS, only 4% of IVDAs and essentially no hemophiliacs with AIDS have evidence of this
neoplasm. Unlike the traditional form, AIDS-associated KS can be very aggressive, often
appearing over the face, neck, upper trunk, and lower extremities, as well as the oral and
pharyngeal mucosa. KS can also present as neck masses secondary to lymph node
infiltration. The typical KS lesion is pink to purplish in color and slightly raised or
nodular. These lesions usually produce minimal symptoms unless they become ulcerated
or secondarily infected or cause functional problems such as airway obstruction. Figure
21.2 demonstrates the typical histologic appearance of KS.

FIGURE 21.2. This photomicrograph demonstrates the
histopathologic findings of Kaposi's sarcoma of the
tongue. Note the proliferation of submucosal spindle cells
(open arrows) surrounding slitlike vascular channels
(solid arrow) with extravasated red blood cells.



The striking difference in incidence rates among different HIV-infected populations has
always introduced the intriguing possibility that a second infectious agent may be
responsible for KS. Recent evidence suggests that a second herpeslike virus may play a
role in KS.
The treatment of AIDS-associated KS is primarily palliative. Although a variety of
modalities, including low-dose radiation therapy, chemotherapy, and immunotherapy, has
been used with some success, the treatment of choice remains controversial. Although
low-dose radiation therapy is particularly effective for dermatologic lesions, mucosal KS
is more resistant to this therapy. Painful mucositis associated with radiation therapy
occurs at much lower radiation doses in AIDS patients, often limiting further treatment.
The argon and carbon dioxide lasers can be useful for local control of some lesions, and
photodynamic therapy has offered a promising alternative for AIDS patients with oral
KS. A recently introduced and often very effective technique for managing isolated KS
lesions is the use of intralesional vinblastine. This palliative technique has been used
successfully for lesions throughout the upper aerodigestive tract, including the larynx (5).
In most patients with KS, survival is determined by other infectious complications of
AIDS and not by KS.
A summary of diagnosis, treatment, and complications of dermatologic conditions is
presented in Table 21.1, Table 21.2 and Table 21.3.

TABLE 21.1. DIAGNOSIS DERMATOLOGIC
CONDITIONS



TABLE 21.2. TREATMENT DERMATOLOGIC
CONDITIONS



TABLE 21.3. COMPLICATIONS
DERMATOLOGIC CONDITIONS



Otologic
Primary dermatologic conditions such as KS and seborrheic dermatitis can also occur in
the external auditory canal of AIDS patients. These conditions often become
symptomatic when there is secondary infection or obstruction of the canal. Management
is the same as for similar dermatologic conditions occurring elsewhere.
Cutaneous P. carinii infection can present as a subcutaneous cyst; it has also been
reported to cause external auditory canal obstruction. With surgical biopsy, the organism
is apparent within the cells of the lesion, and medical therapy usually results in a rapid
clinical resolution.
Serous and acute otitis media are the most common otologic conditions seen in HIV-
infected patients. This is particularly true in pediatric patients in whom eustachian tube
dysfunction, typical of this age group, combined with depressed cell-mediated immunity
increases the susceptibility to infection. In adults, eustachian tube dysfunction resulting
from nasopharyngeal lymphoid hypertrophy, a common finding in HIV-infected adults,
also contributes to middle ear disease. Although the usual middle ear pathogens are
similar for both HIV-infected and nonHIV-infected patients, infections with unusual
organisms can occur. Staphylococcus and Pseudomonas acute or chronic otitis media is
more common in these patients, and P. carinii and Candida have been cultured from
middle ear aspirates of AIDS patients with otitis media. Tympanocentesis is often helpful
to identify middle ear pathogens, especially in the later stages of AIDS when
opportunistic infections have appeared in other locations. Mycobacterial and fungal
cultures and routine bacterial cultures should be obtained so that medical management
can be directed at the correct pathologic organism. A careful evaluation of the
nasopharynx must also be performed to identify neoplastic processes such as KS or NHL
in adults with eustachian tube dysfunction.
Mild to moderate sensorineural hearing loss is often reported in HIV-infected patients.
Although the etiology of this loss is unclear, a viral infection of either the CNS or the
peripheral auditory nerve is suspected. Although the increased latencies found on the
auditory brainstem testing suggest central demyelination consistent with such an
infection, other possible causes such as ototoxic antibiotics, other CNS infections, and
neoplasms must always be considered.
A recent report noted that the more immunocompromised a patient's status, the more
advanced was the stage of otologic disease at presentation. When surgical intervention is
necessary, the risks must be balanced against the potential for improvement, much as in
the case of a severe diabetic, because the incidence of complications is higher. Most
patients in this series tolerated mastoidectomy satisfactorily (6).
Nose and Paranasal Sinuses
As in most anatomic areas of the head and neck, the nose and nasopharynx can also be
sites of herpetic lesions, KS, and NHL. Giant herpetic ulcers can extend from the nasal
vestibule onto the adjacent facial skin and are often resistant to oral antiviral agents. KS
and NHL usually result in nasal obstruction and occasionally involve the paranasal
sinuses and nasopharynx.
Complaints of nasal obstruction and thick postnasal rhinorrhea are very common in HIV-
infected patients, and recurrent and chronic sinusitis often develops despite medical
therapy. Persistent low-grade viral or bacterial infection of the nasal ostiomeatal complex
or edema secondary to the active allergic response of the nasal mucosa may contribute to
this predilection for paranasal sinus infection.
Chronic sinusitis is a common problem as immune function diminishes (7). Although
many unusual organisms have been reported, the usual bacterial pathogens causing HIV-
related chronic sinusitis include Staphylococcus species, Streptococcus pneumoniae,
Haemophilus influenzae, and anaerobic bacteria. Pseudomonas aeruginosa has also been
implicated in up to 20% of patients with HIV-related chronic sinusitis (8). Because this
organism must be included when planning empiric antibiotic therapy, the combination of
ciprofloxacin and clindamycin can provide appropriate coverage until cultures can be
obtained.
In patients with persistent sinus symptoms and a CD4 count of less than 200, unusual
pathogens should be considered and a culture obtained. These patients often respond to
surgical drainage, though most continue to have some nasal symptoms postoperatively.
For individuals with pain out of proportion to findings on examination and radiographic
imaging despite being on empiric antibiotics, the clinician should consider the possibility
of invasive fungal sinusitis. Definitive diagnosis for this devastating infection requires
tissue examination.
The increased prevalence of sinusitis in HIV-infected patients does not appear to be
related to IgE-related immediate hypersensitivity but rather to be secondary to a
decreased cellular immunity. When there is clinical suspicion of sinusitis but the
endoscopic exam is unremarkable, computed tomography is a valuable adjunct to
establish the diagnosis (9).
Oral Cavity and Pharynx
The most common oral and oropharyngeal manifestation of AIDS is mucosal candidiasis,
or thrush. Although this infec-tion typically presents as tender white pseudomembranous
or plaquelike lesions with an underlying erythematous raw mucosal surface, the less
typical atrophic or chronic hypertrophic form can also be seen. The diagnosis is easily
confirmed with a potassium hydroxide (KOH) smear of scrapings from a lesion,
revealing typical candidal budding yeast forms or hyphae. When thrush is accompanied
by severe odynophagia, hypopharyngeal or esophageal candidiasis should be considered.
If initial medical therapy does not produce symptomatic improvement, a barium swallow
or esophagoscopy can help to establish this diagnosis. Systemic antifungals such as
ketoconazole, fluconazole, and amphotericin B are often necessary in these cases.
Herpetic ulcers of the oral mucosa are common in HIV-infected patients. These usually
start as a small group of extremely painful vesicles over the palatal, labial, buccal, or
gingival mucosa and coalesce to form large ulcerative lesions measuring up to several
centimeters. These slow-healing ulcers usually respond to acyclovir; topical steroids are
often helpful to control local symptoms. Giant aphthous ulcers, not of viral origin, are
also commonly seen. Although usually difficult to manage, these lesions can respond to
topical and occasionally to intralesional or systemic steroid therapy.
The generalized cervical lymphadenopathy found in HIV-infected patients can also
involve the lymphoid tissue of Waldeyer ring. Although the resultant adenotonsillar
hypertrophy is usually asymptomatic, a case of airway obstruction due to tonsillar
hypertrophy has been reported. Histopathologic examination reveals severe follicular
hyperplasia similar to that seen in the cervical lymphadenopathy of HIV-infected patients
(10).
The oral and oropharyngeal mucosa is a common site for KS. Unlike the dermatologic
lesions, oral KS frequently ulcerates or becomes secondarily infected, resulting in severe
odynophagia or dysphagia. In one study, 44% of patients with dermatologic KS also had
submucosal lesions of their upper aerodigestive tract. In a few rare cases, KS lesions have
resulted in airway obstruction, necessitating emergent intervention. Management of
mucosal KS is similar to that for the dermatologic variety and has been previously
described.
Ulcerative lesions of the tongue or oropharynx, especially the tonsils, can also be caused
by NHL. This is the second most common neoplasm associated with AIDS. NHL is much
more aggressive and high grade in these patients than in their nonHIV-infected
counterparts. Extranodal sites are involved in 89% of patients, and 42% have CNS
extension. Diagnosis can be made with biopsy of the lesion. Treatment with
chemotherapy and, in some cases, radiotherapy has been somewhat successful in
controlling these tumors, although recurrences are common. Other malignancies, such as
squamous cell carcinoma and Hodgkin's lymphoma, have also been rarely reported in
AIDS patients, but the association of these processes with the HIV infection is not clear.
Hairy leukoplakia is a white vertically corrugated lesion that appears along the anterior
lateral border of the tongue and occurs almost exclusively in HIV-infected patients. This
condition is probably caused by the Epstein-Barr virus and is a reliable prognostic
indicator of AIDS. The probability of developing AIDS is 50% at 16 months and up to
80% at 30 months in patients with hairy leukoplakia.
Aggressive periodontal disease is a common early finding in the HIV-infected patient.
The associated necrotizing ulcerative gingivitis can be very painful and result in marked
gingival recession. Oral antibiotics may be required to control the acute infection.
Although diligent oral hygiene, with frequent antibacterial mouth rinse, can minimize
progression and prevent periodontal complications in some patients, this process often
continues despite these aggressive measures.
A summary of diagnosis, treatment, and complications of oral and pharyngeal conditions
is presented in Table 21.4, Table 21.5 and Table 21.6.

TABLE 21.4. DIAGNOSIS ORAL AND
PHARYNGEAL CONDITIONS



TABLE 21.5. TREATMENT ORAL AND
PHARYNGEAL CONDITIONS



TABLE 21.6. COMPLICATIONS ORAL AND
PHARYNGEAL CONDITIONS



Larynx
When the HIV-infected patient presents with hoarseness, several etiologies in addition to
the typical causes of hoarseness must be considered. Fungal, viral, and mycobacterial
infections of the larynx can cause throat discomfort or hoarseness if the vocal folds are
involved. When laryngeal symptoms persist, biopsy and culture must be considered so
that appropriate therapy can be instituted. KS and NHL can also occur in the larynx and,
when associated with obstructive symptoms, may necessitate surgical intervention.
Neck
Salivary gland disease is often encountered in HIV-infected patients. Xerostomia is a
common complaint in AIDS patients, and histopathologic findings similar to Sjgren
syndrome have been described in salivary gland tissue. Generalized parotid enlargement
has been reported in 30% of HIV-infected children and is caused by a lymphocytic
infiltration of the gland parenchyma. In adults, parotid masses can result from the usual
parotid neoplasms, KS, NHL, or lymphoepithelial cysts. The diagnosis can often be
quickly established with fine-needle aspiration biopsy. Lymphoepithelial cysts in HIV-
infected patients, which have been well described, usually involve the tail of the parotid
and are often bilateral. On radiographic imaging, they are usually multiloculated and
contained within the parotid fascia. Surgical excision alone often results in recurrence.
Aspiration of cystic contents can provide temporary symptomatic improvement, but
recurrence is almost universal. Tetracycline sclerosis has been performed with some
success, but further study is needed before this therapy can be recommended (11). The
incidence of second branchial cleft cysts also increases in AIDS patients. The
pathophysiology of this association is unclear.
Because of the high incidence of baseline palpable lymphadenopathy in HIV-infected
patients, evaluation of cervical masses can be difficult. Previous experience with
excisional biopsy of cervical lymph nodes revealed follicular hyperplasia in most cases.
Despite the higher incidence of NHL and KS in AIDS patients, stable lymphadenopathy
requires observation only. Table 21.7 lists recommended situations in which open biopsy
may be indicated for cervical lymphadenopathy. Fine-needle aspiration biopsy can often
provide valuable information without the need for formal open biopsy. In addition to
malignancies, the differential diagnosis should include tuberculous, atypical
mycobacterial infections, histoplasmosis, toxoplasmosis, and cat-scratch disease (12).

TABLE 21.7. INDICATIONS FOR CERVICAL
LYMPH NODE BIOPSY



OCCUPATIONAL RISKS AND PREVENTION
As the pathophysiologic mechanisms of HIV infection were elucidated, concern for
possible occupational transmission to health care workers became an important issue.
Although these risks have generally been accepted as relatively small, the potentially
fatal consequences of HIV infection cause grave concern on this issue. As of June 1996,
the CDC had positively identified 51 health care workers who had been occupationally
infected. Of these, most (44 patients) had been exposed to needlestick or similar
percutaneous injuries, 5 had mucosal or nonintact skin exposure, 1 had both percutaneous
and mucosal exposure, and 1 had an unknown route of exposure. Additionally, another
108 patients either had not been definitely associated with an occupational exposure or
were under investigation by the CDC. The major flaw in evaluating this case study data is
the lack of a denominator to allow an accurate assessment of occupational risk. Several
prospective cohort studies have evaluated the risk of seroconversion as a function of
discrete exposure events. Based on data from these studies, the calculated risk of
seroconversion after percutaneous exposure is 0.31% (approximately 1 in 300).
The risk of HIV for health care workers is real. Although the cumulative risk of infection
is a function of the seroprevalence rates in specific patient populations, the continuous
expansion of the epidemic into previously unaffected regions of the United States poses a
potential risk to essentially all health care workers. In response to this possibility, the
CDC has issued recommendations for universal precautions, stating simply that all
patients should be assumed to be infectious for HIV and other bloodborne pathogens.
This recommendation is little more than practicing appropriate infection control measures
that should otherwise be part of everyday otolaryngologic practice. Furthermore,
although reducing the risk of HIV infection, these precautions also reduce the risk of
hepatitis among health care workers, an infection currently associated with greater
morbidity and mortality than HIV. This policy also obviates the necessity of patient
screening for HIV, because the precautions are applied to all patients. Specific measures
applicable to the otolaryngologist are found in Table 21.8.

TABLE 21.8. UNIVERSAL PRECAUTIONS FOR
THE OTOLARYNGOLOGIST



The CDC has also issued policy guidelines for the management of occupational exposure
to HIV. In addition to educational programs to inform health care workers about risks and
precautions, a system should be easily and immediately available for promptly initiating
evaluation, counseling, and follow-up after potential HIV exposures. The guidelines also
emphasize that the confidentiality of the health care workers and the source individual
should be maintained at all times.
When a substantial exposure occurs from a known HIV-positive source, the only
currently available treatment option is postexposure prophylaxis with AZT. Postexposure
prophylaxis guidelines have recently been modified by the CDC. Despite limited data,
postexposure prophylaxis is now recommended for occupational exposures with a high
risk for transmission. This recommendation derives from a case-control study of health
care workers given AZT, 1,000 mg/day for 3 to 4 weeks after high-risk exposures. A 79%
decrease in the risk of seroconversion after percutaneous exposure to HIV-infected blood
was observed for those given AZT. This study reported a particularly increased risk of
seroconversion with the following types of exposures: a deep injury to the health care
worker, visible blood on the device causing the injury, injury caused by a device
previously placed in the source patient's vein or artery (e.g., a needle used for
phlebotomy), and exposure from a source patient who died as a result of AIDS within 60
days postexposure (and therefore was presumed to have a high titer of HIV). In addition
to AZT alone, San Francisco General Hospital offers a new postexposure prophylaxis
protocol of AZT and another reverse transcriptase inhibitor, lamivudine, for 28 days.
Initial experience with combination antiviral therapy has been very promising. In certain
high-risk exposures or in cases in which the HIV is suspected to be drug resistant, a
protease inhibitor, indinavir, is also added. Updated information regarding
chemoprophylaxis will be available on the Internet at the CDC's home page
(http://www.cdc.gov/). The current recommendations for AZT prophylaxis at San
Francisco General Hospital are shown in Table 21.9.

TABLE 21.9. RECOMMENDATIONS FOR
POSTEXPOSURE ZIDOVUDINE PROPHYLAXIS



Our medical knowledge and understanding of AIDS continue to expand. As a result, the
evaluation, treatment, and long-term management of patients infected with HIV will be
continually changing. The widespread nature of this epidemic makes it important that
otolaryngologists keep abreast of this rapidly evolving area of medicine so that HIV
disease can be readily identified, available treatment can be initiated, health care workers
can be protected from accidental exposure, and the privacy and civil rights of all infected
persons can be adequately protected.

HIGHLIGHTS
Although it takes approximately 10 years for 50% of patients to
develop AIDS after initial infection with HIV, median survival
is currently only 53 months after the diagnosis of AIDS is
established.
HIV is a retrovirus that relies on the viral enzyme reverse
transcriptase to convert viral RNA into DNA. This DNA is
incorporated into the host cell DNA, thus creating a
permanent infection of the host cell.
Immunodeficiency due to HIV is related primarily to the loss of
helper T lymphocytes. This produces a defect in the cell-
mediated immune system.
The most common AIDS-associated malignancies are KS and
NHL. Although squamous cell carcinoma appears to occur
commonly in these patients, no definite correlation has been
demonstrated.
Serous or acute otitis media is very common in those with HIV
infection. This may be related to nasopharyngeal lymphoid
hypertrophy, which is also common.
Sinusitis is very often seen in HIV disease. This condition often
becomes chronic, in which case response to surgical drainage is
usually favorable.
Hairy leukoplakia is a condition occurring along the lateral
tongue margin and is probably caused by Epstein-Barr virus.
Occurring almost exclusively in HIV-infected patients, it is a
reliable predictor of the development of AIDS. Eighty percent
of patients with this finding develop AIDS within 30 months.
Oral candidiasis is common during the course of HIV disease. It
can present as the typical exfoliative form but is often seen as a
flat erythematous atrophic form. Biopsy is often required to
establish the diagnosis before medical therapy.
The risk of developing HIV infection after a needlestick from
an infected source is approximately 1 in 300. Treatment with
AZT is currently recommended by the CDC for postexposure
HIV prophylaxis following high-risk exposures.
CHAPTER REFERENCES
1. Centers for Disease Control and Prevention, Divisions of HIV/AIDS Prevention.
www.cdc.gov/nchstp/hiv_aids/pubs/facts/intrnatl.htm. November 1999:1.
2. Kitchen VS, Skinner C, Ariyoshi K, et al. Safety and activity of saquinavir in HIV infection.
Lancet 1995;345:952.
3. Centers for Disease Control and Prevention. 1993 Revised classification system for HIV infection
and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Morb
Mortal Wkly Rep 1992;41(RR-17):119.
4. Marcusen DC, Sooy CD. Otolaryngologic manifestations of acquired immunodeficiency
syndrome. Laryngoscope 1985;95:401.
5. Tami TA, Sharma P. Intralesional vinblastine therapy for Kaposi's sarcoma of the epiglottis.
Otolaryngol Head Neck Surg 1995;113:283285.
6. Kohan D, Giacchi RJ. Otologic surgery in patients with HIV-1 and AIDS. Otolaryngol Head Neck
Surg 1999;121:355.
7. Armstrong M, McArthur JC, Zinreich SJ. Radiographic imaging of sinusitis in HIV infection.
Otolaryngol Head Neck Surg 1993;108:3643.
8. Tami TA. The management of sinusitis in patients infected with the human immunodeficiency
virus (HIV). Ear Nose Throat J 1995;74:360363.
9. Garcia-Rodriguez JF, Corominas M, Fernandez-Viladrich P, et al. Rhinosinusitis and atropy in
patients infected with HIV. Laryngoscope 1999;109:939.
10. Kraus DH, Rehm SJ, Orlowski JP, et al. Upper airway obstruction due to tonsillar
lymphadenopathy in human immunodeficiency virus infection. Arch Otolaryngol Head Neck Surg
1990;116:738.
11. Echavez MI, Lee KC, Sooy CD. Tetracycline sclerosis for treatment of benign lymphoepithelial
cysts of the parotid gland in patients infect-ed with human immunodeficiency virus. Laryngoscope
1994;104:14991502.
12. Lee KC, Cheung SW. Evaluation of the neck mass in human immunodeficiency virus infection.
Otolaryngol Clin North Am 1992;25:12871305.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

22 OLFACTORY FUNCTION AND DYSFUNCTION
Head & Neck SurgeryOtolaryngology
22




OLFACTORY FUNCTION AND DYSFUNCTION
RICHARD L. DOTY
DANIEL A. DEEMS

R.L. Doty: Smell and Taste Center and Department of OtorhinolaryngologyHead and Neck Surgery,
University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.
D.A. Deems: Department of Surgery, Sarasota Memorial Hospital; University Ear, Nose and Throat
Associates, Sarasota, Florida.


Intranasal Chemosensation
Anatomy of the Main Olfactory System
Olfactory Transduction and Odor Coding
Olfactory Disorders
Terminology
Causes of Olfactory Loss (Anosmia and Hyposmia)
Causes of Olfactory Distortions (Dysosmia)
Causes of Heightened Smell Function (Hyperosmia)
Influences of Aging on the Ability to Smell
Dementia-related Olfactory Dysfunction
Clinical Assessment and Patient Management
Clinical History
Physical Examination
Olfactory Testing
Psychophysical Tests
Electrophysiologic Tests
Neuropsychological Testing
Neuroimaging
Detection of Malingering
Olfactory Biopsies
Patient Management
Conductive Olfactory Loss
Sensorineural Olfactory Loss
Conclusion
Acknowledgments
Chapter References
The sense of smell serves as a sentinel for assessing the quality of the air entering the
respiratory system, alerting the individual of environmental pollutants, smoke, and
numerous toxic agents. Such a function is of considerable consequence, as the average
adult breathes in approximately 15 kg of air each day, in contrast to taking in only
approximately 1.5 kg of food and 2 kg of water, and even small amounts of pollutants can
pose a significant burden on the respiratory tract (1). Warning agents added to natural gas
by public works companies capitalize on the extreme sensitivity of this sensory system to
airborne chemicals, and olfaction is the first sensory system to detect volatiles arising
from spoiled foods and beverages. Aside from aiding in the avoidance of dangerous
environments and foodstuffs, this primary sensory modality plays a significant role in
mediating a wide range of aesthetic pleasures and largely determines the flavor of foods
and beverages. Indeed, most patients presenting with complaints of decreased taste
function have, in fact, loss of olfactory function, reflecting decreased effectiveness of
retronasal stimulation of the receptors by flavor molecules arising from food during
deglutition (2).
Olfactory loss or distortion is of considerable personal and practical significance to the
patient, particularly ones whose lifestyle, livelihood, or immediate safety depends on a
normal sense of smell (e.g., cooks, firemen, homemakers, plumbers, professional food
and beverage tasters, employees of natural gas works, chemists, and numerous industrial
workers). Importantly, subtle alterations in smell function, often detectable only by
quantitative testing, can be an early sign of such neurological disorders as Alzheimer
disease (AD) and idiopathic Parkinson disease (PD)disorders where early
pharmacologic intervention can be critical. Unfortunately, some patients are notoriously
inaccurate in describing the current state of their chemosensory function. Hence, it
behooves the otolaryngologist to be familiar with modern means for accurately and
objectively assessing olfactory function in the office setting, including means for
detecting malingering. Many patients who believe they have a smell problem do not upon
objective testing, whereas others are unaware of a clear deficit.
The goal of this chapter is to provide the otolaryngologist with a basic understanding of
the anatomy and physiology of the olfactory system, practical ways to accurately and
quantitatively assess its function, and a guide for identifying and managing patients with
common olfactory disorders. The reader is referred elsewhere for more comprehensive
treatises on this general topic (3,4,5 and 6).
INTRANASAL CHEMOSENSATION
Most land mammals possess, within their left and right nasal chambers, elements of five
specialized neural systems: the nervus terminalis or terminal nerve system (cranial nerve
[CN] 0), the main olfactory system (CN I), the vomeronasal or accessory olfactory
system, the trigeminal somatosensory system (CN V), and the septal organ of Masera, an
olfactory receptor-like epithelium on the anterior ventral septum. Adult humans possess
at least three of these intranasal systems (namely, CN 0, CN I, and CN V) and a
rudimentary and nonfunctional vomeronasal organ at the base of each side of the nasal
septum.
CN I mediates what we commonly term smell and, as noted above, is responsible for
most so-called flavor sensations. Technically speaking, CN I is the aggregate of 40 or so
olfactory nerve bundles or fila that course from the olfactory epithelium into the brain via
the foramina of the cribriform plate. The fila contain axons from millions of the receptor
cells surrounded by ensheathing Schwann celllike mesoaxons. These structures pierce the
pia mater, with the receptor axons eventually forming the first layer of the olfactory bulb,
where they branch and synapse with the dentrites of second order neurons in the second
layer of the bulb, the glomerular layer. In most vertebrates, including humans, the
number of olfactory receptor cells exceeds that of any other sensory system except vision.
The free nerve endings of CN V, dispersed throughout the nasal mucosa (including the
olfactory neuroepithelum), mediate, via both chemical and nonchemical stimuli,
somatosensory sensations (e.g., irritation, burning, cooling, and tickling), and induce
reflexive responses, such as secretion of mucus and halting of inhalation, that prevent or
minimize chemically or thermally induced injury to the nasal and pulmonary passages.
Most odorants, at least at higher concentrations, induce some degree of CN V activity (7),
and there is suggestion that CN I and CN V may physiologically interact. Thus, anosmics
reportedly have, as a consequence of their anosmia, lessened CN V function, as measured
electrophysiologically (8), and anesthetizing CN V alters electrophysiological responses
of CN I to odorants (9). There is question, however, as to the significance of such
interactions at the psychophysical level (10).
CN 0, which was discovered after the other cranial nerves had been named, is highly
conserved and remarkably consistent across all vertebrate species, including humans (11).
Its peripheral component is a loose plexus of fine nerve fibers within the nose that is
distinguished by the presence of ganglia at nodal points. Notable for its high
gonadotropin-releasing hormone content, CN 0 ramifies throughout the nasal epithelium
before crossing the nasal mucosa and coursing through the cribriform plate. Although the
function of CN 0 in humans is unknown, in some species it plays a significant role in
reproduction. For example, deficits in mating occur in male hamsters after its central
rootlets are severed, and tactile-induced lordosis in female hamsters is facilitated after
such lesions (12). The gonadotropin-releasing hormone content of the nervus terminalis is
regulated, at least in part, by estrogen (13).
ANATOMY OF THE MAIN OLFACTORY SYSTEM
The neuroepithelium of the main olfactory system is a pseudostratified columnar
epithelium situated on the cribriform plate and segments of the superior septum and both
the superior and middle turbinates (Fig. 22.1). This epithelium is comprised of at least six
morphologically and biochemically distinct cell types (14), although additional classes of
less well-defined microvilli-containing cells have been noted prenatally (15) and
postnatally (16). The first cell type of note is the bipolar receptor cell, which projects
from the nasal cavity into the brain without an intervening synapse, thereby providing a
major route of viral and xenobiotic invasion into the central nervous system. Although
the cilia of these cells are organized in the familiar 9 + 2 microtubule arrangement, they
differ from those of the respiratory epithelium in being much longer, lacking dynein arms
(hence, intrinsic motility), and containing seven domain transmembrane receptors that
interact with odorant ligands. Collectively, the surface area of the cilia exceeds 22 cm
2
in
the human (17) and 7 m
2
(m!) in the German Shepherd dog (18). The second cell type is
the supporting or sustentacular cell. These cells, which have microvilli rather than cilia,
insulate the bipolar receptor cells from one another and help to regulate the composition
of the mucus. They are also involved in deactivating odorants and assist in protecting the
epithelium from foreign agents. The supporting cells contain xenobiotic-metabolizing
enzymes (e.g., cytochrome P-450), a feature shared with the acinar and duct cells of
Bowman glandsglands responsible for most of the mucus adjacent to the olfactory
neuroepithelium. The third cell type is the poorly understood microvillar cell located at
the epithelial surface (19). Some microvillar cells, which resemble the so-called brush
cells of the upper and lower airways of many species, may extend axonlike processes to
the olfactory bulb. Like the supporting cells, they have microvillae at their apical surfaces
(20). In the human, microvillar cells occur in about a 1:10 ratio with the bipolar receptor
cells. A chemosensory function of these cells has yet to be demonstrated, and preliminary
in vitro patch clamp studies of dissociated microvillar cells have failed to find them
responsive to odorants (N. Rawson, personal communication). The fourth cell type lines
the Bowman glands and ducts, whereas the fifth and six cell types are the horizontal
(dark) and globose (light) basal cellscells located near the basement membrane from
which the other cell types arise. Recent data suggest that, under conditions of marked
damage to the olfactory epithelium, the same type of basal cell, most likely a globose
cell, seems to have the potential for giving rise to neurons and nonneural cells, including
the horizontal basal cells, implying a multipotency in stem cells not previously
recognized (14). Unfortunately, in humans cell regeneration in response to injury is rarely
complete, when present at all, and appears to be significantly altered by age and
numerous metabolic factors.

FIGURE 22.1. Freeze-fracture electron micrograph of
the olfactory receptor neuroepithelium; arrow shows
receptor cell with cilia in inverted position; central
umbilicated ovoid structure represents a red blood cell.
Dense matting largely consists of the olfactory cilia. (By
permission, R. M. Constanzo.)



It is now believed that each receptor cell expresses a single odorant receptor gene and
that approximately 1,000 different types of receptors are present within the vertebrate
olfactory epithelium (21). From a genetic perspective, the sense of smell is critically
important for the organism, as the olfactory receptor genes account for approximately 1%
of all expressed genes of the genome, reflecting the largest known vertebrate gene family.
A given type of receptor is not randomly distributed across the receptor sheet but
confined to one of several nonoverlapping striplike zones that in rodents is roughly
parallel to the dorsal-vental axis of the cribriform plate (22). Menco and Jackson (23),
using scanning electron microscopy, recently showed a possible morphologic correlate to
these zones. By embryonic day 16, the posterior regions (roughly corresponding to zones
1 and 2) have much higher receptor cell knob densities than the more anterior regions
(corresponding to zones 3 and 4). Furthermore, the supporting cell microvilli are longer
in region 1 than in region 2, and the tops of cells adjacent to the receptor cells are flatter
in regions 1 and 2 than in regions 3 and 4. Regions 3 and 4 also have glandular openings
and scattered microvillar cells that resemble hair cells of the inner ear. Each class of
odorant receptor appears to project its axons to a limited number of glomeruli within the
olfactory bulb, although all seem to use a single neurotransmitter at their synapse
(glutamate) (24).
Each olfactory bipolar receptor neuron makes its first synapse with the dendrites of the
second order neurons (mitral and tufted cells) within a glomerulus, a globelike structure
located within the olfactory bulb. Although younger persons have thousands of these 50-
to 200-m structures, arranged in single or double layers within the second
glomerularlayer of the bulb, they decrease in number with age and are nearly absent in
persons over the age of 80 years. Their development and maintenance depend on trophic
influences of the receptor cells. A given receptor neuron projects to only one glomerulus,
and a given glomerulus receives most of its input from a restricted zone of the epithelium.
The apical dendrites of the mitral and tufted cells receive synapses not only from the
bipolar receptor neurons but also from interneurons and centrifugal fibers originating
within the granular cell layer, most of which are GABAergic or dopaminergic (25).
The third olfactory bulb layer, the external plexiform layer, contains the cell bodies of the
tufted cells. These cells extend dendrites into the glomeruli and send axons through the
olfactory tract. The fourth layer, the mitral cell layer, contains cell bodies of the large
mitral cells which also project dendritic processes into the glomerili and axons through
the olfactory tract. Synaptic contacts occur within the external plexiform layer of the bulb
between granule cells (cells important in modulation of the afferent signal) and the mitral
and tufted cells. Although commonly divided into lateral and medial olfactory tracts
in textbooks of anatomy, there is no medial tract in primates (26). The primary olfactory
cortex is comprised of the anterior olfactory nucleus, the prepiriform cortex, the lateral
entorhinal cortex, the periamygdaloid cortex (a region contiguous with the underlying
amygdala), and the cortical nucleus of the amygdala. Major connections between the
primary olfactory cortex and the secondary olfactory cortex of the orbitofrontal region
occur via the mediodorsal nucleus of the thalamus and via direct corticocortical
projections from prorhinal cortex to the posterolateral orbitofrontal region.
OLFACTORY TRANSDUCTION AND ODOR CODING
Although, as noted above, a given receptor cell seems to express only one type of
receptor derived from a single allele, each cell is electrophysiologically responsive to a
wide, but circumscribed, range of stimuli (27). This implies that a single receptor accepts
a range of molecular entities and that coding occurs via a complex cross-fiber patterning
of responses. Most, if not all, of the olfactory receptor proteins are linked to the
stimulatory guanine nucleotide-binding protein G
olf
(28). When stimulated, they activate
the enzyme adenylate cyclase to produce the second messenger cAMP (29). G
olf
-induced
cAMP diffuses through the cell and activates cellular depolarization via the opening of
cyclic-nucleotide-gated ionic channels and Ca
2+
-dependent Cl

or K
+
channels (30,31).
The amount of adenylate cyclase activity produced by various odorants in a frog ciliary
preparation (32) is positively correlated with the magnitude of the frog's
electroolfactogram (EOG; a surface potential associated with the number of receptors
activated) (29) and with the perceived intensity of these same odorants to humans (33).
Some odorants also activate cGMP, which is believed to play a role in the modulation of
the sensitivity of olfactory receptor neurons, such as during adaptation (34). Although G
proteins other than G
olf
(e.g., G
i2
and G
o
) have been identified in olfactory receptor cells,
they appear not to be involved in early transduction events, likely assisting in such
processes as axonal signal propagation, axon sorting, and target innervation (35).
OLFACTORY DISORDERS
Terminology
Anosmia refers to loss of the ability to smell, whereas hyposmia or microsmia refers to
decreased ability to smell. Total anosmia denotes an inability to smell all odorants on
both sides of the nose. Partial anosmia implies an inability to smell certain odorants. In
some cases, partial anosmia is indicative of decreased sensitivity to a broad spectrum of
odorants (general hyposmia), with the decrement exceeding the absolute threshold for
only some odorants. Specific anosmia, the lack of ability to smell one or a few odorants
in the presence of an otherwise normal sense of smell, is rarely a reason for medical
consultation. Hyperosmia reflects abnormally acute smell function. This condition occurs
only rarely (e.g., in some unmedicated epileptic patients). Olfactory dysfunction can be
either bilateral or unilateral (sometimes termed binasal or uninasal). Loss of olfaction on
both sides of the nose is referred to as bilateral anosmia or, as noted above, total anosmia.
Dysosmia is distorted or perverted smell perception, with parosmia and cacosmia
denoting a change in the quality of an olfactory cue (e.g., a flower smelling rancid) and
phantosmia denoting odor perception in the absence of an olfactory stimulus (e.g.,
olfactory hallucinations).
Causes of Olfactory Loss (Anosmia and Hyposmia)
Chemosensory disorders originate from a multitude of causes (Table 22.1) and may be
the consequence of normal aging. When damage to the olfactory receptors or to central
neural structures involved in olfactory transduction is the basis of the dysfunction, the
problem is due to sensorineural factors. This occurs, for example, when contre-coup
movement of the brain in trauma sheers the olfactory axons at the level of the cribriform
plate. When intranasal problems, such as blockage from nasal polyps, are the basis of the
olfactory dysfunction, the condition is due to conductive factors (36,37). In some cases, it
is difficult to classify an olfactory disorder into these two mutually exclusive categories,
as both blockage of airflow to the receptors and damage to the receptors and/or more
central elements of the olfactory system can be simultaneously present. Although many
cases of olfactory dysfunction due to conductive factors are treatable, most olfactory
disorders due to sensorineural factors are untreatable.

TABLE 22.1. EXAMPLES OF REPORTED
ETIOLOGIES FOR OLFACTORY DYSFUNCTION



Numerous factors can produce decrements in olfactory function. Nearly two thirds of
cases of chronic anosmia or hyposmia (i.e., those presumably permanent) are due to prior
upper respiratory infections, head trauma, and nasal and paranasal sinus disease, and
most reflect permanent damage to the olfactory neuroepithelium (2). Other causes include
iatrogenic interventions (e.g., septoplasty, rhinoplasty, turbinectomy, radiation therapy),
intranasal neoplasms (e.g., inverting papilloma, hemangioma, and
esthesioneuroblastoma), intracranial tumors or lesions (e.g., Foster Kennedy syndrome,
olfactory groove meningiomas, frontal lobe gliomas), epilepsy, psychiatric disorders,
exposure to environmental chemicals, and hypothyroidism. According to Finelli and Mair
(38), the single most egregious error of neurologists is failure to recognize the symptom
of anosmia as the principal or sole feature of an olfactory groove neoplasm. Importantly,
5% to 10% of head trauma cases exhibit olfactory dysfunction, with most having anosmia
(36,37).
Causes of Olfactory Distortions (Dysosmia)
Most dysosmias reflect dynamic elements associated with degeneration (or, more rarely,
regeneration) of the olfactory epithelium and remit over time. Thus, it is common for
patients with anosmia from such causes as head trauma and upper respiratory infections
to report that before onset of their anosmia they experienced a period of weeks or months
when dysosmia was present. Some cases of extremely debilitating chronic dysosmia
(usually of a number of years duration and often unilateral), where weight loss is marked
or daily functioning is markedly impaired, are amenable to surgical intervention (e.g.,
ablation of regions of the olfactory epithelium or olfactory bulb removal). Of the surgical
approaches, intranasal ablation or stripping of tissue from the olfactory epithelium on the
affected side is more conservative and less invasive than removal of the olfactory bulb
and/or tract via a craniotomy (39). If the dysosmia reappears after such surgery,
additional intranasal ablations can be performed. In most cases, demonstrable smell loss
does not accompany the dysosmic condition, implying a requirement for a relatively
intact sensory system for expression.
In rare instances dysosmias present as auralike hallucinations presumably associated with
central (e.g., temporal lobe) dysfunction. In many such cases, no seizure activity can be
documented, and no evidence of central nervous system lesions or tumors is apparent.
Nonetheless, low doses of anticonvulsant medication may be effective in mitigating the
frequency and severity of some of these dysosmias. Dysosmias also occur in a wide range
of psychiatric disturbances that usually are diagnosed on other grounds (e.g., psychosis).
Infrequently, dysosmia may be due to the perception of foul odors produced by the body,
such as those from purulent nasal secretions in sinusitis or from exhalations in halitosis or
uremia. Other disorders that may present as dysosmia include trimethylaminuria (fish
odor syndrome) and cat odor syndromea pediatric neurologic disorder associated with
a -methyl-crotonyl-CoA carboxylase deficiency. Such rare disorders usually exist in the
presence of a normally functioning olfactory system.
Causes of Heightened Smell Function (Hyperosmia)
In contrast to cases of anosmia, hyposmia, and dysosmia, cases of hyperosmia
(heightened smell function) are rare if, indeed, existent. Although untreated adrenal
cortical insufficiency has been reported to produce hyperosmia in humans, this has not
been confirmed, and animal studies have found no evidence for hypersensitivity after
adrenalectomy (40). There have been suggestions of hyperosmia in syndromes such as
multiple chemical sensitivity, but the limited data available also fail to support this notion
(41). Hyperosmia reportedly occurs in some cases of epilepsy during the interictal period,
although, as noted above, most patients with long-term epilepsy and intractable seizure
activity, such as candidates for temporal lobe resection, are hyposmic (42).
Influences of Aging on the Ability to Smell
It is important to realize that disorders of smell function, particularly loss or decreased
smell ability, are not uncommon in the general population and increase with age (Fig.
22.2). Unfortunately, such losses often go unnoticed, and physicians rarely assess smell
ability quantitatively in the same way that they assess visual or auditory acuity. Under the
age of 65 years, approximately 1% of the population has major difficulty smelling.
Between 65 and 80 years, this increases remarkably, with about half of the population
experiencing significant decrement in the ability to smell. Over the age of 80, this figure
rises to nearly 75% (43). It is significant that smell dysfunction is not only a potential
early sign of nasal sinus disease but of such debilitating neurodegenerative diseases as
AD and idiopathic PD.

FIGURE 22.2. University of Pennsylvania Smell
Identification Test (UPSIT) scores as a function of age
and gender. Numbers by data points represent sample
sizes. (From Doty RL, et al. Smell identification ability:
changes with age. Science 1984;226:14411443, with
permission.)



Dementia-related Olfactory Dysfunction
Considerable research has been devoted to the study of olfactory dysfunction in
dementia-related diseases. Of particular interest is the observation that olfactory
dysfunction may be the first sign of AD and idiopathic PD (44). In the case of AD, limbic
brain regions that receive the olfactory bulb mitral and tufted cell projections tend to be
the brain regions with the highest concentration of neurofibrillary tangles and neuritic
plaques (45). In PD, bilateral olfactory deficits occur before the onset of most of the
classic neurologic signs and symptoms and are unrelated to disease stage, use of
antiparkinson medications, duration of illness, and symptom severity, such as masked
faces, tremor, rigidity, bradykinesa, or gait disturbance (46,47 and 48).
Although the olfactory loss in AD and PD is pervasive and marked, this is not true of a
number of other neurodegenerative disorders, and olfactory testing can be helpful in
establishing a differential diagnosis. For example, patients with essential tremor and
those with progressive supranuclear palsyconditions that share many motor symptoms
with PDhave little or no olfactory dysfunction (49). Similarly, patients with
parkinsonism secondary to intravenous exposure to the proneurotoxin, 1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridine, appear to have relatively normal olfactory function
(50). Recently, it has been shown that the olfactory loss associated with multiple sclerosis
is directly proportional to the number of multiple sclerosis-related plaques in central brain
regions associated with olfactory processing (i.e., inferior middle temporal lobe and
periorbital frontal cortex) (51).
CLINICAL ASSESSMENT AND PATIENT MANAGEMENT
Clinical History
To understand chemosensory dysfunction, it is imperative that the clinician decipher a
basic confusion that can confound accurate diagnosis. In an evaluation of 750 patients
with chemosensory dysfunction, it was demonstrated that although most patients present
with complaints of both smell and taste loss, few (less than 5%) have identifiable whole-
mouth gustatory deficits. This is due largely to a descriptive confusion between taste
(i.e., true gustation) and flavor, which reflects to a large degree the olfactory-derived
sensations from foods. Specifically, the perception of poor ability to taste during
deglutition usually reflects loss of flavor sensations derived from retronasal olfactory
stimulation rather than to loss of taste-bud mediated sensations, per se (52). Thus, such
flavors as chocolate, coffee, vanilla, strawberry, pizza, licorice, steak sauce, root beer,
and cola disappear when CN I is damaged, leaving intact only sweet, sour, salty, bitter,
and perhaps umami (monosodium glutamate-like) sensations. Whole-mouth taste
function is much more resistent to injury than olfactory function, largely due to the
redundancy of innervation of the gustatory system (i.e., CN VII, IX, and X). Although
seemingly a simplistic concept, this is the first consideration in the decision tree for
diagnosis and treatment of olfactory disorders.
The semantic confusion between taste and flavor can also be expanded to include certain
dysosmias, in that patients may confuse dysgeusia (taste distortion) with dysosmia,
perceived as flavor distortion. For example, a foul taste may represent a retronasal
dysosmia that occurs during deglutition. To differentiate, the clinician must know that the
taste (an actual dysosmia) typically is described using terms such as chemical-like or
rancid rather than terms reflecting distortion of a true gustatory quality (e.g., bitter). In
other words, patients with true dysgeusias generally can assign a distinct taste quality to
the sensory distortion (e.g., salty or bitter) (2,53).
A patient's description of the nature and onset of the chemosensory problem is essential
to the clinical history. The same is true of an assessment of the patient's past medical and
surgical histories, with an emphasis on such areas as endocrinologic state, history of
radiation therapy, and medications taken before symptom onset (such as thyroid
supplementation, high doses of antibiotics, antihypertensive medications, or
antineoplastic agents). Delayed puberty in association with anosmia (with or without
midline craniofacial abnormalities, deafness, and renal anomalies) suggests the
possibility of Kallmann syndrome. Importantly, associated events are critical for
establishing an etiologic diagnosis (e.g., viral or bacterial respiratory tract infections,
head trauma, exposure to toxic fumes, systemic diseases, and signs of early dementia,
parkinsonism, or central tumors). Information about or signs or symptoms of toxic
chemical exposure and seizure activity (e.g., automatisms, occurrence of black outs, deja
vu, etc.) should be sought, particularly in cases where heightened sensitivity is a
complaint. Decreased olfactory function has been observed in some persons infected with
the human immunodeficiency virus.
In patients complaining of anosmia or hyposmia, it is useful to ask whether smell
function is diminished or completely absent, localized to one or the other nasal chamber
(or both), and whether the dysfunction is for all odorants or only a few. Patients with loss
due to nasal or paranasal sinus disease are more likely to indicate a gradual loss of
function than those whose loss is due to a prior upper respiratory infection or to head
trauma (2). Some patients with olfactory dysfunction secondary to nasal or paranasal
sinus disease report temporary recovery of function under circumstances in which nasal
patency is increased. For example, function may return during warm days, exercise,
showering, or treatment with topical or systemic corticosteroids, implying a deficit in
stimulus delivery to the olfactory cleft (as in allergic rhinitis) rather than solely a
sensorineural problem.
Smoking history should be explored, in light of evidence that olfactory ability decreases
as a function of cumulative smoking dose and that cessation of smoking can result in
improvement in olfactory function over time (54). A history of allergy should be sought,
as should a history of current or past nasal or paranasal sinus infection. Inquiry should be
made about previous nasal or paranasal sinus surgery, although olfactory deficit after
such surgery has been shown to be rare (55). Importantly, the association of nasal
obstruction, headache, facial pain, postnasal discharge, purulent or clear rhinorrhea,
otologic symptoms, and throat symptoms should be sought with specific questioning.
The order in which symptoms appeared and regressed is at times helpful. The duration of
the problem is of importance in relation to the possibility of spontaneous recovery, which
is generally assumed to be minimal after 6 months if damage to the olfactory epithelium
is implicated. In the case of conductive olfactory loss, if olfactory function returns
intermittently, then olfactory receptors are present, regardless of the disease duration
(56). The patient should be queried also about olfactory distortions and whether they
seem bilateral or unilateral. If the problem is present while the patient is being examined,
have the patient hold shut both sides of the nose and the left and right sides separately to
ascertain if the problem requires airflow to the receptors and, if so, whether the problem
is localized to the left or to the right. If such localization exists, then the rhinologist can
focus attention on the involved side of the nose. Exploring a complaint of taste loss is
very important, because this usually reflects an olfactory disorder. It is useful to have the
patient distinguish between the loss of the perception of flavor of food or beverages and
the loss of the perception of sweet, sour, bitter, and salty stimuli. Inquiring as to whether
the patient can perceive saltiness in potato chips, sourness in lemonade, or sweetness in
sugar on cereal can help in this differentiation. An anosmic will be able to taste the
sweetness of an apple or a pear but will be unable to distinguish between their flavors or
to taste chocolate.
Physical Examination
Essential components of the physical examination include a complete otolaryngologic
examination with an emphasis on anterior rhinoscopy and nasal endoscopy, both flexible
and rigid, allowing for a thorough assessment of the olfactory cleft. The nasal mucus
membranes should be examined for color, surface texture, swelling, inflammation,
exudate, ulceration, epithelial metaplasia, erosion, and atrophy. When pansinusitis is
present, the anosmic etiology is obvious. However, very minor polypoid disease at the
olfactory cleft can also account for major olfactory dysfunction (56). Helpful on nasal
endoscopy is the finding of mucopus above the eustachian tube orifice, suggesting
posterior ethmoid and/or sphenoid disease, whereas mucopus below the eustachian tube
suggests disease involving elements of the osteomeatal complex. The presence of polyps,
masses, adhesions of the turbinates to the septum, and marked deviations of the septum
all have the potential for adversely influencing airflow to the olfactory epithelium,
because a mere 15% of inspired air typically traverses the olfactory cleft in the
unobstructed state (57). Importantly, there is a false-negative rate of nearly 50% with
anterior rhinoscopy when compared with nasal endoscopy (56). Allergy is suggested if
the mucous membrane is pale, usually as a result of edema within the lamina propria.
Chronic or acute exposure to environmental or industrial pollutants is suggested by
metaplasia within the epithelium and by swelling, inflammation, exudate, erosion, and
ulceration. Atrophy of the lamina propria is suggested by unusual spaciousness, dryness,
and crusting, as is seen in atrophic rhinitis.
Complete neurologic evaluation is also necessary, emphasizing cranial nerve function
and attention to possible skull base and intracranial lesions. Optic disk examination
should be performed to determine the presence of increased intracranial pressure
(papilledema), particularly in cases of unilateral olfactory dysfunction, because tumors of
the olfactory groove or sphenoidal ridge (e.g., meningiomas) can cause Foster Kennedy
syndrome, comprised of ipsilateral anosmia or hyposmia, ipsilateral optic atrophy, and
central papilledema.
Olfactory Testing
Accurate assessment of olfactory function is essential to establish the validity of a
patient's complaint, characterize the specific nature of the problem, reliably monitor
changes in function over time (including those of iatrogenic etiology), detect
malingering, and establish compensation for permanent disability. It should be noted that
many patients complaining of anosmia or hyposmia actually have normal function
relative to their age and gender. Others may be unaware of their deficits. For example,
approximately 90% of patients with idiopathic PD have a demonstrable smell loss, yet
less than 15% are aware of their problem until tested objectively (46).
Olfactory evaluation often has both medical and legal consequences. As stated earlier,
anosmia or hyposmia is common in head injury (2,37) and often is the only residual
neurologic impairment from falls and motor vehicle accidents. Importantly, malingering
is commonly detected using olfactory tests with malingering scales, such as the
University of Pennsylvania Smell Identification Test (UPSIT; see next section), that
should be administered in cases where litigation is involved. In Great Britain, disability
benefits for anosmia resulting from an injury are available under the National Insurance
Act and under private accident insurance policies. In the United States, disability
compensation is provided for under the 1963 amendment to the Workman's
Compensation Law when decreased future earning power is apparent. Whereas the
Veterans Administration awards a 10% whole body disability for total anosmia, the
Guides to the Evaluation of Permanent Impairment published by the American Medical
Association suggests only a 3% compensation, a figure we consider woefully inadequate.
In practice, both the Veterans Administration and the American Medical Association
impairment guidelines are exceeded in many legal settlements for anosmia. It should be
noted that occupation should be taken into account in disability issues, as loss or
decreased smell function is particularly significant for persons in some occupations (e.g.,
chefs, plumbers, wine tasters, municipal gas workers).
Traditionally, physicians have examined the ability to smell by asking a patient to sniff a
few odorous items (e.g., coffee, cinnamon, or tobacco in small vials) and to report
whether or not an odor is perceived. Unfortunately, this procedure is analogous to testing
vision by shining a flashlight into each eye and asking whether or not a light is seen.
Asking the patient to identify the odor does not correct the situation, because even normal
subjects have difficulty identifying some odors without cueing. Despite the fact that most
olfactory disorders are discernible using various nominally distinct olfactory tests (e.g.,
tests of odor detection, discrimination, identification, and memory), the interpretation of
the findings of such tests must be made conservatively. For example, all such tests are
influenced by damage to the olfactory neuroepithelium, making it dangerous to assume,
in any given case, that poor performance on a specific type of test (e.g., odor memory)
has anything to do with damage to neural circuits underlying the name of the test (e.g.,
odor memory circuits) (58). Presently, there is no way to distinguish between central and
peripheral deficits on the basis of psychophysical or electrophysiological testing. The fact
that the reliability (and hence sensitivity) of a number of olfactory tests is low or
unknown adds further difficulty in attempts to establish differential function.
Although most olfactory problems are bilateral and bilateral testing reflects the better
functioning side of the nose, in some instances unilateral testing is warranted. To
accurately assess olfaction unilaterally, the naris contralateral to the tested side should be
occluded without distorting the patent nasal valve region to prevent or minimize crossing
of inhaled or exhaled air at the rear of the nasopharynx to the opposite side (so-called
retronasal stimulation). An easy way of doing this is to seal the contralateral naris using a
piece of Microfoam tape (3M Corporation, Minneapolis, MN) cut to fit the naris borders.
The patient is instructed to sniff the stimulus normally and to exhale through the mouth.
Psychophysical Tests
Despite the fact that a wide range of psychophysical olfactory tests are available for
accurately assessing olfactory function, most are of unknown reliability and validity,
cumbersome, and suffer for lack of normative data. Fortunately, during the last few years
a handful of standardized and practical psychophysical tests have been developed,
including several brief self-administered screening tests (e.g., 59,60,61 and 62). The most
widely used of these tests is the UPSIT, known commercially as the Smell Identification
Test (Sensonics, Inc., Haddonfield, NJ) (59,60) (Fig. 22.3). This test, which is available
in English, Spanish, French, and German language versions, has been administered to
nearly 200,000 patients since its invention in the early 1980s. The UPSIT can be self-
administered in 10 to 15 minutes by most patients in the waiting room and scored in less
than a minute by nonmedical personnel. This test consists of four booklets containing 10
odorants apiece. The stimuli are embedded in 10- to 50-m diameter microencapsulated
crystals located on scratch and sniff strips on the bottom of the pages of the test
booklets. Above each strip is a multiple choice question with four response alternatives.
The patient is required to choose an answer, even if none seems appropriate or no odor is
perceived (i.e., the test is forced choice). This encourages the patient to carefully sample
all of the stimuli and provides a means for detecting malingering; because chance
performance is 10 of 40, very low scores reflect avoidance, and hence recognition, of the
correct answer. Norms based on the administration of this test to nearly 4,000 people are
provided and an individual's percentile rank established relative to persons of the same
age and gender. This test also makes it possible to classify an individual's function, on an
absolute basis, into one of six categories: normosmia, mild microsmia, moderate
microsmia, severe microsmia, anosmia , and probable malingering. The reliability of this
test is very high (test-retest Pearson r = 0.94).

FIGURE 22.3. University of Pennsylvania Smell
Identification Test (UPSIT; commercially known as the
Smell Identification Test

or SIT, Sensonics, Inc.,


Haddon Heights, NJ). This 40-item microencapsulated
odor (scratch and sniff) test consists of four test
booklets, each containing 10 odorants with four-
alternative response answers to each. Norms for this test
are based on nearly 4,000 subjects spanning the entire age
range. (Photo courtesy of Sensonics, Inc., Haddon Heights, NJ.)



Electrophysiologic Tests
Although two electrophysiologic procedures are available for assessing olfactory
function, their application is still largely experimental and confined to university centers
where the necessary equipment and expertise are available for their application. The first
of these proceduresodor event-related potentials or OERPsconsists of discerning
synchronized brain electroencephalographic activity recorded from the surface of the
scalp from overall electroencephalographic activity after brief presentations of odorants.
To obtain accurate potentials, stimuli are presented in a precise manner (e.g., with rise
times less than 30 ms) using equipment that produces stimuli embedded within a warmed
and humidified airstream (Fig. 22.4). Averaging of responses from repetitive stimulation
is used to increase the signal-to-noise ratio.

FIGURE 22.4. Temperature, and humidity controlled
stainless steel environmental chamber for testing of odor
event-related potentials. Right: data collection port;
center: olfactometer; left: subject being presented with
olfactory stimuli and performing a computerized visual
attention task. (Photo courtesy of the University of
Pennsylvania Smell and Taste Center, Philadelphia.)



Although evoked potentials of this sort are definitive when clearly present, they are not
so when weak or absent, and the measurement of such potentials in the clinic has severe
practical limitations. Because stimuli can only be presented every half minute or so
(because of adaptation problems), large numbers of trials cannot be practically collected
on a patient, in contrast to the case of the thousands of trials that can be obtained in a
brief period of time in analogous visual and auditory paradigms. Thus, the reliability of
the data is suspect in cases where movement and other artifacts require elimination of a
significant number of trial records. Unlike visual and auditory evoked potentials, no
inference can be made regarding the location of a lesion or deficit with this technology,
because only late field potentials are large enough to be reliably discerned with the
number of trials that are available. Thus, altered amplitude or latency of OERPs can
reflect airway obstruction or dysfunction anywhere along the afferent pathway, including
the olfactory epithelium, bulb, primary olfactory cortex, and possibly secondary olfactory
cortex. Because the quality of the late field potentials depends on the alertness of the
subject, uncooperative subjects who do not attend to the task at hand can produce
misleading potentials. Despite such shortcomings, however, OERPs can be useful in
some cases in detecting malingering and are generally sensitive to alterations in olfactory
function due to a wide range of causes.
Another electrophysiologic procedure that has been used in human olfactory
measurement is the EOG (63). The EOG, which is measured from an electrode placed on
the surface of the olfactory epithelium, represents mainly summated generator potentials
of olfactory receptor neurons. The recording of the EOG is more difficult than that of the
OERP, and far fewer patients are amenable to such recordings. The placement of the
recording electrode is under endoscopic guidance, but because local anesthesia must be
avoided, the placement of the electrode can be quite unpleasant and sneezing and mucous
discharge is common. Importantly, even after the placement of the electrode into the
appropriate area, the EOG cannot be recorded in many subjects. This may be due to the
topographic distribution of specific olfactory receptors in combination with the relatively
few number of odorants used or the presence of age-related metaplasia of respiratory-like
epithelium within the olfactory epithelium.
NEUROPSYCHOLOGICAL TESTING
Given the close association between olfactory loss and several forms of dementia,
including AD and multiinfarct dementia, brief neuropsychological testing is warranted in
some cases to determine the presence of dementia (64). The Mini-Mental State
Examination is a widely used brief screening instrument for dementia and can be
administered in the otolaryngologist's office in a few minutes to determine if further
referral is necessary. More extensive dementia assessment is time consuming and best
left in the hands of the neuropsychologist. Such assessment often is made using either the
Mattis Dementia Rating Scale, the Blessed Dementia Scale, the Boston Naming Test, or
the logical memory and visual reproduction subtests of the Wechsler Memory Scale-
Revised. The Wechsler Memory Scale-Revised and the California Verbal Learning Test
have proved useful in cases where schizophrenia is suspected.
NEUROIMAGING
Computed tomography (CT) has proven invaluable in identifying soft tissue disease and
bony changes within the sinonasal cavities. Olfactory dysfunction of idiopathic etiology
warrants CT of the nasal cavity, paranasal sinuses, anterior skull base, and, if central
causes of olfactory dysfunction are suspected, the brain as well. Coronal scans are
particularly valuable for assessment of the paranasal anatomy and may help identify such
entities as limited polypoid disease in the olfactory cleft. Contrast enhancement is useful
to better identify vascular lesions, neoplasms, abscesses, and meningeal or parameningeal
processes. Presently, high-resolution CT appears to be the most useful and cost-effective
screening tool to assess sinonasal tract inflammatory disorders.
Magnetic resonance imaging (MRI) is superior to CT in discriminating soft tissue
changes but is less sensitive than CT in identifying bony abnormalities or landmarks.
Thus, MRI is the technique of choice to evaluate the olfactory bulbs, olfactory tracts, and
intracranial causes of olfactory dysfunction. For instance, MRI can be used to confirm
agenesis of the olfactory bulbs in Kallman syndrome (65) and degeneration in many
cases of trauma-related anosmia (66). The technique used at the Smell and Taste Center
involves MRI using a 12.7-cm-round general purpose surface coil centered on the nasion
beginning with a sagittal localizing scan, followed by coronal images with the parameters
500/15/2 (repetition time/echo time/excitations) obtained with 3-mm interleaved scans
and a 256 256 matrix. These are followed by 3-mm interleaved coronal fast spin-echo
T2-weighted images with the parameters 2,000/84/2 and a matrix of 256 192. Finally,
gadolinium-enhanced MRI is particularly valuable in detecting dural or leptomeningeal
involvement and to distinguish solid tumors from rim-enhancing inflammatory processes
(67).
DETECTION OF MALINGERING
Malingering sometimes occurs in patients seeking insurance settlements or other
restitution for negligence claims. Often malingering occurs on taste tests rather than smell
tests, because bonafide smell loss is present and the patient is unable to malinger on the
olfactory test but attempts to embellish the gustatory tests in the direction of loss,
confusing loss of flavor with loss of taste. On forced-choice psychophysical tests, such as
the UPSIT, malingering appears as the reporting of fewer incorrect responses than
expected on the basis of chance. The theoretic probability of a true anosmic having an
UPSIT score five or less is less than 0.05. The theoretic probability of a true anosmic
scoring 0 on the UPSIT is less than 0.00001. Malingering is suspected if patient reports
smell loss yet a clear OERP is documented. Evidence for a general tendency to malinger
can also be obtained using neuropsychological tests specifically designed for this purpose
(e.g., tests sensitive to head trauma patients trying to fein memory disturbances). Among
those that are widely used is the Rey Memory Test, also known as the Rey 3 5 Test and
the Rey 15-item Memory Test (64). The rationale behind this test is that malingerers
typically fail at a memory task that all but the most developmentally disabled or severely
brain injured persons perform easily.
OLFACTORY BIOPSIES
In rare instances, biopsies of the olfactory neuroepithelium can be obtained to assess
damage to this region of the olfactory system. In this procedure, a small amount of
olfactory neuroepithelial tissue is removed from the superior nasal septum by the
rhinologist and analyzed histologically (68). This procedure must be performed by a
surgeon experienced in the technique, and multiple biopsies are usually needed to obtain
true neuroepithelium, given the considerable age-related metaplasia of respiratory-like
epithelium within the region of the olfactory neuroepithelium (69). Because of the latter
problem, sampling issues arise and negative biopsies are difficult to interpret.
PATIENT MANAGEMENT
Conductive Olfactory Loss
In cases of conductive olfactory loss, where the anosmia or hyposmia is caused by airway
obstruction, treatment to relieve the edema or physical obstruction can be undertaken
with optimism. Pre- and postintervention olfactory testing is needed to establish
intervention efficacy and to screen for subsequent slow relapse, so characteristic of most
conductive disorders. Examples of treatments that have restored olfactory function
include allergy management, topical and systemic corticosteroid therapies, antibiotic
therapy, and various surgical interventions, including functional endoscopic sinus
surgery. A brief course of systemic steroid therapy is often useful in distinguishing
between conductive and sensorineural olfactory loss, as patients with the former will
often respond positively to the treatment, although longer term systemic steroid therapy is
not advised. Topical nasal steroids are ineffectual, in some patients, in returning smell
function because the steroid fails to reach the affected regions in the upper nasal
passages. Having the patient administer the spray or drops while in the Moffett position
(i.e., with the head upside down, as when hanging the head over the side of the bed in the
morning while in the supine position) can increase efficacy in some of these cases.
Although, as noted earlier in this chapter, rigid nasal endoscopy is very useful in
diagnosing anosmia secondary to nasal pathology, the decision to perform endoscopy
cannot be based solely on patient complaint, because approximately a third of patients
with positive endoscopies deny frank nasal obstruction. Also, a negative endoscopic
examination does not rule out an obstructive etiology. Thus, fine-cut coronal CT is
frequently warranted in patients with conductive olfactory loss for both diagnosis and
operative planning (56).
Sensorineural Olfactory Loss
It appears likely that most cases of olfactory dysfunction stem from damage to the
olfactory epithelium. Progressive changes occur in this epithelium soon after birth, and
metaplasia to respiratory epithelium into the olfactory epithelium is a common
phenomenon (69). Animal studies have noted that exposure to airborne toxic chemicals,
including cigarette smoke, cause widespread alterations in the olfactory epithelium. Such
alterations likely explain the finding of dose-related alterations in olfactory sensitivity in
current and previous cigarette smokers (54) and the effects of exposure to low levels of a
variety of airborne chemicals on olfactory function (70). Interestingly, rats raised in a
pathogen-free environment appear to have olfactory receptor cells that are relatively long
lived, suggesting that much of the metabolic and regenerative activity in the olfactory
epithelium is induced by environmental agents (71). With respect to smoking-induced
anosmia, not only is olfactory decline related to cumulative smoking dose, but extent of
spontaneous recovery is directly related to the duration since cessation of smoking (Fig.
22.5) (54). Thus, optimism for future return of function in hyposmic cigarette smokers
upon smoking cessation is warrented in most cases.

FIGURE 22.5. Effect on smell ability of cumulative
smoking dose and years since smoking cessation for
previous smokers (n = 197). UPSIT, University of
Pennsylvania Smell Identification Test. (From Frye RE,
et al. Dose-related effects of cigarette smoking on
olfactory function. JAMA 1990;263:12331236, with
permission.)



For sensorineural loss related to presbyosmia, no current treatment regimen has yet been
developed to reestablish complete olfactory function. The one half or so of the elderly
patients in the general population who are microsmic do find it comforting to know that
their presbyosmia may be normal for their age and gender, using current testing
paradigms (particularly the UPSIT). Making the patients aware of their deficit is
essential, in that a disproportionate percentage of individuals involved in natural gas-
related accidents are of pensionable age (57,58,72). This is due to the fact that
mercaptan, the pungent odor in natural gas, is an olfactory and not trigeminal stimulant.
Because age-related sensorineural loss is frequently gradual, the patient may be unaware
of the deficit and may not present to the clinician until they experience a near catastrophe
with a gas appliance. Thus, careful counseling of this group is necessary. Many older
individuals who suffer from hyposmia have also found it useful to hyperflavor their
foods in an attempt to bring back the pleasurable aspect of eating. Again, counseling
should focus on healthy additives, such as a hyperflavored strawberry food bar and no
oversalting, which is often an early response to hyposmia. Clearly, loss of food flavor
as part of the normal aging process alters quality of life and may have a negative impact
on the nutritional staus of the individual (2).
For patients with dysosmia, a careful review and systematic cessation of drugs potentially
associated with the dysfunction may be fruitful in some instances, although this process
can take months, depending on the mode of action of the drugs involved and the number
of medications being taken by the patient. In rare cases of long-term chronic dysosmia
severe enough to produce depression, weight loss, or nausea due to the perversion of food
flavor, surgical intervention may be indicated as described in detail earlier in this chapter.
Treatment of patients with anosmia due to sensorineural problems is challenging.
Although there are a few advocates of zinc and vitamin therapies, as well as such agents
as theophylin, sound empirical evidence of their efficacy is lacking and untoward side
effects of some such therapies are common (2). In cases where olfactory loss has been
present for a long period of time and can be attributed to neural damage within the
olfactory neuroepithelium, prognosis is poor and no treatment is possible. Nevertheless,
simply providing such patients with accurate information about their disorder,
establishing objectively the degree and nature of the deficit, and ruling out the possibility
of a more serious disorder as the cause of their problem can be very therapeutic. Because
half of elderly persons with permanent olfactory loss will fall at or above the 50th
percentile of their normative group on the UPSIT, half of elderly patients can be
informed that while they are performing below the level that they used to perform, they
are still outperforming most of their peers. This is extremely therapeutic and helps them
place the natural age-related loss of olfactory function into a broader perspective.
CONCLUSION
The past several decades have brought forth a blossoming of our understanding of
olfactory disorders, with the knowledge that olfactory dysfunction accompanies a wide
array of diseases, including AD and idiopathic PD. Clearly, our ability to treat olfactory
disorders must begin with accurate diagnoses and careful selection of patients for
therapeutic intervention. In this chapter, we have reviewed techniques for achieving these
ends and have presented an overview of the types of disorders commonly associated with
altered olfactory ability. As the average lifespan of the population continues to increase,
otolaryngologists will be called on more frequently to diagnose and manage age-related
chemosensory disorders. Hence, it is imperative that the modern otorhinolaryngologist is
well informed of the nature of such disorders and uses up-to-date methods in their
assessment and treatment.
ACKNOWLEDGMENTS
Supported in part by grants PO1 DC 00161, RO1 DC 04278, and RO1 DC 02974 (to
R.L.D., Principal Investigator) from the National Institute on Deafness and Other
Communication Disorders, National Institutes of Health, Bethesda, Maryland.

HIGHLIGHTS
Peripheral damage to the olfactory receptors and the associated
olfactory mucosa from upper respiratory viral and bacterial
infections, numerous environmental and industrial chemicals,
and chronic nasal disease is common.
Anosmia refers to loss of the ability to smell, whereas
hyposmia, or microsmia, refers to decreased ability to smell.
Total anosmia denotes an inability to smell all odorants on both
sides of the nose. Partial anosmia implies an inability to smell
certain odorants.
Examples of olfactory loss due to conductive factors include
allergy or nasal polyposis, although edema within the olfactory
neuroepithelium or changes in the mucus overlying the
olfactory neuroepithelium also can play a role.
Most reports of taste loss reflect, in fact, altered olfactory
function. Thus, a clear diagnostic distinction should be made
between a true taste disorder (e.g., dysfunction in sweet, sour,
bitter, or salty perception) and an olfactory disorder
misconstrued as a taste problem. Thus, such flavor sensations as
apple, banana, coffee, chocolate, hamburger, strawberry, lemon,
and pizza depend on adequate retronasal stimulation of the
olfactory receptors.
Patients with loss due to nasal or paranasal sinus disease are
more likely to indicate a gradual loss of function than those
whose loss is due to a prior upper respiratory infection or to
head trauma.
Accurate assessment of olfactory function is essential to
establish the validity of a patient's complaint, characterize the
specific nature of the problem, reliably monitor changes in
function over time (including those of iatrogenic etiology),
detect malingering, and establish compensation for permanent
disability.
Olfactory dysfunction of idiopathic etiology warrants CT
imaging of the nasal cavity, paranasal sinuses, anterior skull
base, and, if central causes of olfactory dysfunction are
suspected, the brain as well.
On forced-choice psychophysical tests, such as the UPSIT,
malingering appears as the reporting of fewer incorrect
responses than expected on the basis of chance.
Examples of treatments that have restored olfactory function
include allergy management, topical and systematic
corticosteroid therapies, antibiotic therapy, and various surgical
interventions, including functional endoscopic sinus surgery.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

23 NASAL FUNCTION AND EVALUATION
Head & Neck SurgeryOtolaryngology
23




NASAL FUNCTION AND EVALUATION
THOMAS V. MCCAFFREY

T.V. McCaffrey: Head and Neck Program, H. Lee Moffitt Cancer Center and Research Institute;
Department of OtolaryngologyHead and Neck Surgery, University of South Florida College of Medicine,
Tampa, Florida.


The Nasal Airway
Nasal Blood Vessels
Sympathetic Vasomotor Control
Parasympathetic Vasomotor Control
Other Vasoactive Mediators
Nasal Glands and Secretion
Mucociliary Function
Mucous Blanket
Respiration
Modification of Inspired Air
Nasal Airway Resistance
Control of Nasal Resistance
Action of Dilator Nares
Vascular Control of Resistance
Nasal Cycle
Positional Effect
Nasal Vascular Reflexes
Evaluation of the Nasal Airway
Rhinomanometry
Nasal Aerodynamics
Laminar Flow
Turbulent Flow
Orifice Flow
Collapsible Segments
Measurement of Nasal Resistance
Bilateral Nasal Resistance
Methods of Rhinomanometry
Anterior Rhinomanometry
Posterior Rhinomanometry
Clinical Technique of Rhinomanometry
Reporting Data
Interpretation of Rhinomanometric Findings
Unilateral Nasal Resistance
Total Nasal Resistance
Effect of Decongestion
Airway Collapse
Acoustic Rhinometry
Theory of Acoustic Rhinometry
Characteristics of Rhinograms
Use of Acoustic Rhinograms
Chapter References
The rational evaluation and management of nasal obstruction must be based on an
understanding of the fundamental facts of nasal structure and function. The structure of
the nasal airway is complex, because it is composed of markedly different regions. The
support changes from soft tissue to cartilage to bone. The lining changes from skin to
mucosa. These structural components must be understood in relation to the function of
the nose as an airway and as a protector of the lower airways.
THE NASAL AIRWAY
The nasal mucosa is a complex organ responsible for several of the functions of the nasal
airway. The mucosal surface area of the nasal airway is approximately 150 cm
2
. The
functions of this tissue are to provide heat and fluid exchange for warming and
humidifying inspired air, to alter nasal airway resistance through congestion and
decongestion of the nasal mucosa blood vessels, to clean and filter inspired air by means
of impaction on the moist mucus-coated surface, and to sense the environment with
specialized (olfactory) and general (trigeminal) sensory nerves. These functions are
provided by the nasal blood vessels, nasal glands, and the mucociliary system.
Nasal Blood Vessels
The vascular bed of any organ can be functionally divided into resistance vessels, which
control the blood flow to the organ, exchange vessels, which are responsible for filtration
and absorption of fluid, and capacitance vessels, which are responsible for blood volume.
The resistance vessels are arterioles and precapillary sphincters that account for more
than 80% of the vascular resistance to blood flow. The capillaries are the main exchange
vessels, and the veins are the main capacitance vessels.
The submucosa of the nasal epithelium contains a rich network of highly specialized
blood vessels related to its role of heating and humidifying inspired air. The venous
sinusoids of the nasal mucosa are particularly well developed to control the size of the
nasal airway. Specialized arteriovenous anastomoses allow blood to bypass the capillary
bed and pass directly into the venous sinusoids. Figure 23.1 shows the functional
arrangement of these vessels. The arterioles regulate blood flow to the nasal mucosa by
means of contraction of their precapillary sphincters. The blood flow to the mucosa heats
the inspired air and supplies the venous sinusoids with blood to control airway resistance.

FIGURE 23.1. Functional arrangement of the nasal
vascular system.



Nasal blood vessels receive motor control from both the sympathetic and
parasympathetic nervous systems (1). The sensory nerve fibers in the nasal mucosa can
control nasal blood vessels through release of neurotransmitters during axon reflexes. The
sensory nerves reach the nose primarily in the first and second divisions of the trigeminal
nerve. The sympathetic preganglionic nerves arise in the thoracic spinal cord and travel in
the sympathetic chain to the superior cervical ganglion, where they synapse with the
postganglionic fibers. The postganglionic fibers reach the nasal mucosa through the
vidian nerve. The parasympathetic preganglionic nerves arise in the brainstem and travel
in the facial nerve and greater superficial petrosal nerve to the sphenopalatine ganglion,
where they synapse with postganglionic fibers. The postganglionic parasympathetic
fibers travel to the nasal mucosa with the sympathetic fibers in the vidian nerve.
Sympathetic Vasomotor Control
The blood vessels of the nose are normally under sympathetic vasoconstrictor tone. The
sympathetic neurotransmitter once was thought to be only norepinephrine. Now there is
evidence that other neurotransmitters are involved in the sympathetic effects on the nasal
mucosal blood vessels. These include avian pancreatic polypeptide and neuropeptide Y
(2).
Parasympathetic Vasomotor Control
The main action of the parasympathetic nerves of the nasal mucosa is controlling
secretion; however, there are important parasympathetic vasomotor effects. Studies have
shown parasympathetic dilatation of both capacitance and resistance vessels and
increases in venous volume and blood flow in the nasal mu-cosa. Although the
parasympathetic neurotransmitter has been assumed to be acetylcholine, vasoactive
intestinal polypeptide and peptide histamine isoleucine are related peptides that have
been identified in parasympathetic nerve endings in the nasal mucosa. These peptides
have known vasodilating effects and may play a role in parasympathetic vasodilation of
the nasal mucosa.
Other Vasoactive Mediators
Substance P, a peptide containing 11 amino acids, is present in both the central and
peripheral nervous systems. Substance P has several pharmacologic effects, including
stimulation of smooth muscle, vasodilation, and stimulation of nasal secretion (3).
Substance P mediates vasodilation and increased vascular permeability, and it may be the
neurotransmitter responsible for vasodilation in response to chemical and mechanical
stimulation. Vasodilation of nasal blood vessels is produced by both H
1
and H
2
histamine
receptor agonists. Leukotriene D
4
, another local mediator in immunologic reactions, has
been shown to produce vasodilation. This response may be important in local vasomotor
control during immunologic reactions and may be responsible for the nasal congestion of
allergic rhinitis.
Nasal Glands and Secretion
Secretion of mucus by the nasal glands is an essential component of nasal airway
function. The secretion provides a wetted surface to humidify the inspired air, a means to
entrap and transport particulate material filtered from inspired air, and a fluid
environment for the action of cilia. Mucus is produced by the goblet cells (unicellular
intraepithelial mucous glands) and submucosal mucous and seromucous glands.
Production of mucus is under neural control primarily by the parasympathetic neurons
that reach the mucosa through the vidian nerve. Secretion is stimulated by the release of
acetylcholine from the parasympathetic neurons. This effect is blocked by atropine.
Mucociliary Function
The mucociliary system is an important defense component of the respiratory system but
has special importance for a nasal airway exposed to environmental contamination. The
mucociliary system is composed of the ciliated respiratory epithelium, the mucous
blanket, and the mucus-producing glands. This system provides a mechanism for
maintaining a constantly moist surface for humidification and cleaning of inspired air and
a means to eliminate excess glandular production and debris from the nasal airway. The
nasal respiratory epithelium is pseudostratified ciliated epithelium. Each ciliated cell
contains 50 to 100 cilia 5 to 7 m long. The cilia beat at a rate of 800 to 1,000 strokes per
minute (4). The action of the cilia produces mass movement of the mucous blanket at a
rate of 3 to 35 mm per minute in the human nose.
Mucous Blanket
Lucas and Douglas first described the two-layer structure of the mucous layer. The layer
surrounding the ciliathe periciliary fluidis a serous fluid probably produced by the
ciliated cells themselves. Overlying the periciliary fluid is a viscoelastic mucous layer
produced by the submucosal glands and the goblet cells within the epithelium (Fig. 23.2).
As the cilia beat, the tips of the cilia propel the mucous layer. The direction of transport
of the mucous blanket follows a pattern determined by the orientation of the cilia beat.
Transportation of mucus in the nose is generally in a posterior direction. This ensures
clearance of excess mucus with the entrapped particles into the posterior pharynx, where
it is swallowed. In the sinuses, the pattern of mucus transport is consistently in the
direction of the sinus ostia. In this way, mucus, particulates, and potentially pathogenic
bacteria are cleared from the sinuses. Disruption of this transport system inevitably
results in bacterial sinusitis.

FIGURE 23.2. Nasal mucociliary system. The cilia beat
in the serous fluid layer, and the tips of the cilia engage
the mucous layer during the propulsion phase of the
stroke.



RESPIRATION
The nasal airway is the entrance to the respiratory tract. Although respiration can occur
through the mouth when respiratory demands are high, respiration occurs preferentially
through the nose. The respiratory functions of the nose include preparation of inspired air
for the lower respiratory tract by means of warming and humidification, protection of the
lower airway by means of removing noxious particulates and soluble gas, and regulation
of airway resistance.
Modification of Inspired Air
The upper airways provide an important protective function by heating ambient air to a
temperature of 37C and saturating it with water vapor. This is a suitable environment for
alveolar gas exchange. The demands placed on the upper airway vary with the ambient
conditions of temperature and humidity. The heat for warming and the water for
humidification of the ambient air are provided by the moist, highly vascular mucosa of
the upper airway, particularly the nose. Conditions that reduce the effective surface area
of the nasal mucosa available for exchange, such as atrophic rhinitis, impair this essential
function of the nasal airway.
Nasal Airway Resistance
Resistance of the nasal airway accounts for more than 50% of total airway resistance.
Although humans can breathe through the nose, mouth, or both, breathing during rest is
mainly through the nose. The usual reasons given for the preference of nasal breathing
are (a) improved humidification and warming of inspired air, (b) improved filtering of
particulate matter in the inspired air, and (c) smoothing the pattern of respiration by nasal
resistance. The nasal airway can be divided into three distinct regions, each with a
different mechanism for the physiologic control of nasal resistance. These regions are the
nasal vestibule, the nasal valve, and the nasal cavum (5).
Nasal Vestibule
The nasal vestibule is the skin-lined region beginning anteriorly at the nares and
extending to the level of the caudal end of the upper lateral cartilage. The support of the
vestibule is the alar cartilage and its muscular and fibrous attachments. The nasal alae are
subject to pressure changes during the cycle of respiration. During inspiration there is
relatively negative pressure within the vestibule. Because of the lack of rigid support of
the ala during inspiration, internal negative pressure tends to collapse this segment of the
airway. This tendency is normally largely overcome with activation of the dilator nares
muscles during inspiration. These muscles are innervated by the facial nerve and
normally contract just before the onset of active inspiration (6). With increased
ventilation produced by exercise, activity of the dilator nares muscle increases to prevent
an increase in resistance of this segment of the airway.
Nasal Valve
The nasal valve is the region of the nasal airway extending from the caudal end of the
upper lateral cartilage to the anterior end of the interior turbinate. It is located
approximately 1.3 cm from the nares. This is the narrowest segment of the nasal airway
and is the major flow-resistive segment of the nasal airway (7). Measurements made from
casts of the nasal airway give an average cross-sectional area of 0.73 cm
2
for this region.
In a normal nose, the nasal valve region is the narrowest segment of the nasal airway. As
air enters this constricted segment of the airway, airflow accelerates, and intraluminal
pressure decreases according to the Bernoulli principle. This decrease in pressure can
collapse this segment of the airway during inspiration if the upper lateral cartilage is
anatomically weak or has been surgically detached from the septal cartilage. The erectile
tissues of the nasal septum and tip of the inferior turbinate impinge on the nasal valve.
Engorgement of these tissues can increase the resistance of this segment of the nasal
airway.
Nasal Cavum
The nasal cavum is the region of the nasal airway posterior to the piriform aperture. The
resistance of this segment of the nasal airway is determined primarily by the degree of
engorgement of the erectile tissues of the turbinates and the septum. However, the
relative contribution of this segment of the airway to total nasal resistance is small. Many
studies have shown that the greatest contribution of nasal airway resistance is made by
the anterior nasal airway, even in the state of congestion. Acoustic rhinometry has shown
that the tip of the inferior turbinate narrows the nasal airway just posterior to the nasal
valve. It is here that engorgement of the erectile tissue of the turbinate has the greatest
influence on the resistance of the nasal airway.
Control of Nasal Resistance
The baseline resistance of the nasal airway can be remarkably constant when measured
over a period of days or weeks. Most healthy adults without symptoms of nasal disease
have a nasal resistance ranging from 0.15 to 0.3 Pa/cm
3
per second (8,9). However, nasal
resistance changes with posture, disease, physiologic state, and psychologic factors.
Airway resistance can increase or decrease depending on the physiologic demands for gas
exchange. The major sites for regulation of airway resistance are the dilator nares
muscles of the external nose and the venous sinusoids of the nasal turbinates.
Action of Dilator Nares
The muscles of the external nose, particularly the dilator nares muscles, have phasic
respiratory activity. This activity is enhanced during exercise and during increased
ventilation. The dilator nares muscles have a role in preventing an increase in nasal
resistance by means of dynamic collapse of the ala. In some cases these muscles actually
reduce resistance to airflow during hyperventilation.
Vascular Control of Resistance
The other major factor controlling nasal resistance is the state of vascular congestion of
the nasal mucosa. Because the nasal airway is a rigid bony cavity, changes in the volume
of the nasal mucosa can effectively alter the dimensions of the nasal airway. This fact is
obvious with the severe nasal obstruction that result from congestion of the nasal mucosa
during upper respiratory tract infection. Besides pathologic alterations in the nasal airway
with disease, there is physiologic variability in the nasal airway as a result of vascular
changes.
Nasal Cycle
The nasal cycle is the observed intrinsic variability of the nasal airway resistance that
occurs in a cyclic pattern in as many as 40% of persons (10). This cyclic engorgement
and decongestion of the cavernous tissue of the nose have been known since the
beginning of the nineteenth century. The cycle has a duration of 2 to 6 hours. During the
cycle, one side of the nose congests while the opposite side decongests. This means that
total nasal resistance remains essentially constant despite the localized alternating
congestion of each side of the nose.
Positional Effect
Lateral recumbence produces congestion of the nasal chamber in the lower position and
disrupts the normal cycle of alternating congestion and decongestion (nasal cycle). This
phenomenon is a neural response to stimulation of pressure receptors on the surface of
the body. If pressure is applied to the side of the body, congestion of the ipsilateral side
of the nose occurs.
Nasal Vascular Reflexes
Additional physiologic reflexes affecting the nasal vessels have been studied. Because the
nose is a part of the respiratory tract, it would be expected that the nasal airway would
participate in respiratory reflexes. The phenomenon of nasal decongestion occurring with
hypercapnia has been studied in humans and animals. The reflex reduction in nasal
resistance that occurs with hypercapnia and hypoxia is mediated by the sympathetic
nervous system (11). The reduction in nasal resistance closely follows the increased
ventilation that occurs with these stimuli. Exercise, another known stimulator of
ventilation, also has an effect on nasal resistance. Nasal decongestion occurs promptly
with the beginning of exercise and is proportional to the increase in ventilation that
occurs with the exercise (12).
EVALUATION OF THE NASAL AIRWAY
Evaluation of an obstructed nasal airway requires accurate information about the
anatomic and functional abnormalities producing the symptom of obstruction. With an
accurate knowledge of the anatomic abnormality and its functional consequences, a plan
of treatment based on an understanding of the effects of surgery on the airway can be
formulated. In the past, technical difficulties limited the use of tests of nasal function;
however, methods have been devised to quantify nasal respiratory function. The oldest
and most widely used technique is rhinomanometry. Rhinomanometry is used to measure
the pressure needed to produce airflow through the nasal airway. Various methods have
been used to measure respiratory nasal airflow for at least a century. Because
rhinomanometry does not measure the location of nasal obstruction, it can be of limited
use clinically. The newer technique of acoustic rhinometry shows promise in providing a
measure of the cross-sectional area of the airway at various points. This is accomplished
by means of analysis of sound pulses reflected by the nasal airway.
Rhinomanometry
Rhinomanometry is a technique for measuring nasal airway resistance as a diagnostic tool
for the evaluation of nasal airway function. It allows functional assessment of the
adequacy of the nasal airway and combined with rhinoscopic examination and other
diagnostic techniques allows diagnosis of nasal airway insufficiency. The limitations of
rhinomanometry must be recognized. It does not provide enough information for a
diagnosis or about the cause of nasal obstruction. Rather it provides an objective
measurement of nasal resistance at a specific time (8,9).
Nasal Aerodynamics
A basic knowledge of the characteristics of nasal airflow is necessary to understand the
applications and limitations of rhinomanometry. Airflow through the nose follows the
basic physical laws first elaborated by Poiseuille and Reynolds. However, airflow in the
nose is complicated by the irregular contour of the nasal cavity, areas of marked
constriction and abrupt changes in direction of airflow, regions with collapsible
segments, and areas in which the dimensions of the airway are under muscular and
vascular control. These complicating factors impose limitations on interpretation of nasal
resistance measurements, because the nasal airway cannot be represented as an ideal tube,
as assumed by the simplest physical law of fluid flow.
Laminar Flow
The simplest type of airflow is laminar flow. Laminar flow occurs when there is no gross
mixing in the airstream from one region to another. In this type of flow, the air molecules
follow streamlines, each layer or lamina sliding smoothly past adjacent regions (Fig.
23.3). The resistance to laminar flow depends only on the dimensions of the conduit and
the viscosity of the fluid.

FIGURE 23.3. Diagram shows laminar airflow. In
laminar flow, there is no mixing within the airstream
(arrows). The pressure difference between points P1 and
P2 is linearly related to the flow (V) by a constant (K).



Turbulent Flow
If the flow rate exceeds a critical value, the air molecules deviate from the streamline
flow, and mixing occurs in the fluid. This is called turbulence (Fig. 23.4). Turbulence
occurs when the Reynolds number exceeds 2,000. This corresponds to a flow of
approximately 250 to 500 cm
3
/s in the nose. Under conditions of turbulent flow, a simple
relation between pressure and flow cannot easily be determined. Simplified theoretic
considerations show that in turbulence, pressure is related to the square of flow. When
turbulence occurs, resistance to airflow depends on factors other than the size of the
conduit. During turbulence, factors such as wall roughness and flow separation can
produce differences in the measured resistance of conduits of the same size.

FIGURE 23.4. Diagram shows turbulent airflow. In
turbulent airflow, there is mixing within the airstream
(arrows). The pressure difference between points P1 and
P2 is related to approximately the second power of the
flow.



In the airway, the relation between pressure and flow is more complex, and only an
approximation of the ideal relation between pressure and flow occurs. The curve obtained
is not a linear relation, as would occur if nasal airflow were laminar, but is a sigmoid
curve. Under turbulent conditions, the flow curve departs from the laminar flow curve.
This deviation increases with increasing flow rate. Conditions other than turbulence can
account for the nonlinearity of the pressure-flow relation in the nasal airway. Regions of
orifice flow or collapse of the airway can produce nonlinear pressure-flow relations.
Orifice Flow
When gas flows through a conduit with localized constriction, orifice flow can occur
(Fig. 23.5). Flow through an orifice has a nonlinear pressure-flow relation. The pressure
to produce flow through an orifice depends on the hydraulic cross-section of the orifice.
An orifice smaller than the rest of the lumen determines the resistance of the whole
conduit. This is shown in Fig. 23.5. The orifice is a flow-limiting segment and largely
determines the resistance of the airway. Orifice flow can occur physiologically within the
nasal valve area. This leads to the observation that the flow-limiting segment of the nasal
airway occurs in the region of the nasal valve.

FIGURE 23.5. Diagram shows orifice flow. A short
constriction accelerates the airstream with divergent flow
beyond the constriction. The pressure difference between
points P1 and P2 is related to the second power of the
flow.



Collapsible Segments
Consideration of the resistance properties of the nasal airway often entails the implicit
assumption that the walls of the nasal cavity are rigid. This is valid for flow in the bony
cavum of the nasal airway, but it is not for the compliant region of the nasal vestibule and
valve. The lateral pressure within a conduit depends on the rate of flow, according to the
Bernoulli principle. As airflow accelerates through a constriction, lateral pressure
decreases. Compliance of the area of constriction can allow collapse. Collapse of the
nasal valve can occur, and this factor can lead to a nonlinear pressure-flow relation.
Collapse is characterized by an asymmetric pressure-flow curve during the inspiration
and expiration flow limitation occurring on inspiration.
Measurement of Nasal Resistance
Nasal resistance is the numerical relation between transnasal pressure and flow. Pressure
(P) divided by flow (V) is resistance (R), as follows:
R = P/V
The previous description of laminar flow showed that the relation between pressure and
flow (resistance) is a constant; however, during turbulence, orifice flow, or flow in a
collapsible tube, resistance depends on flow rate, and a nonlinear relation results.
Therefore, the numerically calculated resistance varies from point to point along the
pressure-flow curve (Fig. 23.6). To obtain a consistent value of resistance that can be
compared, it is necessary to specify a specific point on the pressure-flow curve to
calculate resistance. In the accepted method, a specific pressure point (usually 150 or 300
Pa) is selected, and flow is measured at this point.

FIGURE 23.6. Typical curvilinear relation between
pressure and flow for the nasal airway. Because of the
contributions of turbulence and orifice flow, pressure and
flow are not linearly related in the nasal airway.



Bilateral Nasal Resistance
When only unilateral nasal resistance is measured directly, it is still possible to calculate
the resistance of the nasal airway as a whole (right and left sides together). Total nasal
resistance can be estimated with the parallel resistance formula to derive total resistance
(R
c
) from measured right (R
r
) and left (R
l
) resistance:
R
t
= (R
l
R
r
)/(R
l
+ R
r
)
This equation is strictly true only for the laminar flow condition. For nasal resistance, this
equation gives only an approximation because nasal flow is not laminar. This equation is
most nearly correct if the measured resistances are approximately equal. An alternative, if
nasal resistance is measured as a constant pressure point, is to measure exact total
resistance because the flows in parallel resistors are additive. This yields the simple
formula for total resistance:
R
t
= P/(flow
r
+ flow
l
)
Methods of Rhinomanometry
To determine the resistive properties of the nose, it is necessary simultaneously to
measure pressure and flow through the nose. With pressure and flow, a quantitative value
for nasal resistance can be calculated and a graphic representation of the pressure-flow
relation made.
Anterior Rhinomanometry
Anterior rhinomanometry is measurement of transnasal pressure at the anterior end of the
nose. If one nostril is occluded, the pressure in that nostril equals the pressure in the
nasopharynx because the occluded airway can be considered a rigid tube with its
proximal end exposed to nasopharyngeal pressure (Fig. 23.7). If a differential pressure
transducer is inserted into the occluded nostril, the difference between atmospheric
pressure and nasal pressure equals the pressure difference between the nasopharynx and
the air. This is the driving pressure for airflow through the unobstructed nostril. With this
method, resistance can be measured in only one nostril at a time. Total nasal resistance
can be calculated with one of the parallel resistance formulas previously described.

FIGURE 23.7. Diagram shows the technique of anterior
rhinomanometry. The figure is an axial view of the nasal
airway and nasopharynx (NP). The pressure in the
nasopharynx is measured at the nostril (P1) by means of
occluding the nostril with a rubber bulb. Because no
airflow occurs through this side of the nose, the pressure
measured at the nostril (P1) equals the pressure in the
nasopharynx. The flow (V) is measured with a
pneumotachograph attached to a mask.



Anterior rhinomanometry has inherent limitations. It cannot be satisfactorily used in
cases of complete occlusion of one nasal passage. Nasal septal perforation or marked
flaccidity of the septum makes the measurements unreliable. Anterior rhinomanometry
also produces the nonphysiologic condition that all airflow must occur through one side
of the nose during measurement. This means that even under resting conditions the
measurements can be made only over short time periods because breathing may be
restricted when respiration occurs through only one side of the nose. To overcome this
difficulty and allow measurement of nasal resistance of both nostrils simultaneously, the
method of posterior rhinomanometry was developed.
Posterior Rhinomanometry
In posterior rhinomanometry, air pressure in the nasopharynx is measured with a catheter
placed in the mouth. In this technique, the lips are sealed around the catheter so no
airflow occurs through the mouth. Because neither nostril is occluded, it is possible to
measure bilateral nasal resistance directly. The pressure transducer catheter placed in the
mouth accurately measures nasopharyngeal pressure as long as the palate is not
contracted tightly against the base of the tongue, which would occlude the
communication between the oral cavity and the nasopharynx. The difference between
nasopharyngeal pressure and atmospheric pressure is the driving pressure for nasal
airflow.
Clinical Technique of Rhinomanometry
The basic clinical technique of anterior mask rhinomanometry is shown in Fig. 23.8. This
technique has been chosen for routine use because it is reproducible, can be performed
with modest investment in equipment, and provides the data necessary for clinical
evaluation of nasal resistance. Nasal airflow is measured as shown in Fig. 23.8 with a
tightly fitting face mask applied to the face. The mask has a large central aperture
connected to a low-resistance pneumotachograph flowmeter. The pneumotachograph
converts the flow signal to a differential pressure that can be measured with an electronic
pressure transducer.

FIGURE 23.8. Clinical rhinomanometry by means of the
anterior technique. A nasal pressure catheter is used to
measure transnasal pressure and a mask
pneumotachograph to measure airflow. Pressure-flow
relation and resistance are calculated with a computer at a
standard pressure of 150 Pa.



Transnasal pressure is measured at the nostril (anterior rhinomanometry). The pressure-
measuring catheter passes through the mask and is attached to the nostril with either tape
or a soft sponge rubber bulb. It is important that a pressure-tight seal be achieved at the
nostril. A second catheter is used to measure air pressure inside the mask. These two
pressure catheters are attached to a differential pressure transducer to measure transnasal
pressure. The outputs of the electronic pressure transducers are amplified and recorded as
a pressure-flow diagram. Recording can be done with an oscilloscope, an X-Y plotter, or
a computer equipped with appropriate interface electronics and software. Computer-
based rhinomanometry systems meeting these specifications are produced by several
manufacturers. A commercial unit chosen for clinical use should produce a pressure-flow
diagram and standard nasal resistance. In addition to this basic function, several units
provide features that may prove useful in particular circumstances.
Reporting Data
At an international rhinomanometry meeting in 1986 several standards were proposed for
implementation of rhinomanometry. These standards were considered minimal for
reporting and comparing data on nasal airway resistance. The basic method proposed was
anterior mask rhinomanometry as described previously. The minimal reporting value was
chosen as the airflow or resistance calculated at 150 Pa pressure.
Interpretation of Rhinomanometric Findings
Although rhinomanometry provides only one aspect of the clinical evaluation of nasal
obstruction, the information obtained about the functional capacity of the nasal airway
cannot be acquired with other methods of evaluation. In general, there are two major
types of nasal obstruction: mucosal hypertrophy or congestion and structural deformity of
the nasal airway. When nasal resistance is determined before and after maximum nasal
decongestion with a topical decongestant, it is possible to determine the relative
importance of mucosal and structural factors in producing nasal obstruction.
Calculated resistance can be compared with predetermined normal ranges found for
persons without symptoms. Mucosal obstruction usually is expected to be corrected with
topical decongestion. Structural abnormalities causing nasal obstruction are not expected
to be in the normal range after decongestion. Normal nasal resistance values and ranges
have been established. There is not an absolute upper limit of normal nasal resistance;
however, a nasal resistance greater than 0.3 Pa/cm
3
per second usually is symptomatic.
The threshold for subjective obstruction, however, varies. Some persons with apparently
normal or slightly elevated nasal resistance have obstructive symptoms at times. Several
measurements obtained with rhinomanometry provide important information about the
nasal airway. These are unilateral nasal resistance before decongestion, total nasal
resistance before decongestion, the effect of decongestion on nasal resistance, and the
presence of airway collapse.
Unilateral Nasal Resistance
There is considerable variability in unilateral nasal resistance because of normal
physiologic responses, the nasal cycle, and anatomic differences in the nasal airway.
Despite this variability, there is a close correlation between symptomatic obstruction of
the nasal airway and measured nasal resistance when large populations are studied.
Because of differences in individual thresholds for obstruction, it is difficult to set strict
limits on the normal range of unilateral nasal resistance.
Total Nasal Resistance
Total nasal resistance is less variable than unilateral nasal resistance because it
incorporates both nasal airways and thus is not affected by the nasal cycle. For this
reason, it is a better predictor of the presence of obstructive symptoms. A total nasal
resistance greater than 0.3 Pa/cm
3
per second usually is symptomatic and is likely to be
associated with symptoms of severe obstruction (9). Patients treated for nasal obstruction
with septal surgery are more likely to have subjective improvement if the initial nasal
resistance is greater than 0.3 Pa/cm
3
per second (13).
Effect of Decongestion
Nasal decongestion with topical vasoconstrictors decreases nasal resistance. A marked
reduction in nasal resistance after decongestion to a normal value suggests that mucosal
disease (vasomotor rhinitis, allergic rhinitis, or rhinitis medicamentosa) is a major
contributor to the nasal obstruction. If, however, decongestion causes less than a 35%
decrease in resistance, especially if asymmetry persists in the unilateral nasal resistances
after decongestion, a structural cause, such as septal deformity, conchal hypertrophy,
stenosis, or concha bullosa, can be inferred.
Airway Collapse
Rhinomanometry is particularly useful in the diagnosis of nasal obstruction due to
dynamic changes in the nasal airway, because rhinoscopic examination may not detect
these abnormalities. Nasal alar collapse, or nasal valve collapse, is a dynamic
phenomenon in which the resilient cartilaginous and fibrofatty structures of the nasal ala
collapse during inspiration. This phenomenon may be due to localized obstruction in the
nares region that leads to excessive negative pressure in the region of the vestibule and
nasal valve during inspiration. If the negative pressure in the nasal airway is sufficient to
overcome the elasticity of the cartilage, the airway collapses, and nasal resistance
increases with increasing effort. The typical rhinomanometric finding with such collapse
is an asymmetric nasal pressure-flow curve. Because collapse occurs only during
inspiration, inspiratory resistance is higher than expiratory resistance. Collapse produces
flow limitation that can be detected as a plateau on the pressure-flow curve (Fig. 23.9).

FIGURE 23.9. Pressure-flow relation under laminar,
turbulent, and collapse conditions. In laminar flow, the
pressure-flow relation is linear. In turbulent flow
conditions, the pressure-flow relation is curvilinear.
When collapse occurs, there is plateauing of the
inspiratory phase of the cycle and asymmetry between the
inspiratory and expiratory phases.



Acoustic Rhinometry
Acoustic rhinometry is a method of noninvasive measurement of the cross-sectional area
of regions of the nasal airway. The technique is based on analysis of a sound pulse
reflected from the airway. The examination is rapid and noninvasive and requires
minimal cooperation from the subject. The results are reproducible and highly accurate.
A graph is produced of nasal cross-sectional area as a function of distance from the
nostril. Unlike rhinomanometry, acoustic rhinometry does not require nasal airflow. The
main advantage over rhinomanometry in evaluating the nasal airway is the ability to find
narrow segments of the airway. Acoustic rhinometry, however, does not measure the
effect of the narrow regions on airflow dynamics or airway resistance. It is a tool best
used in conjunction with rhinomanometry for functional assessment of the airway.
Theory of Acoustic Rhinometry
Jackson et al. (14) showed it is possible to use reflected acoustic energy to measure the
cross-sectional area of the airways as a function of distance. If an acoustic pulse is
introduced into the airway, the intensity, phase, and time delay of the reflected sound
energy wave are determined by the size and location of narrowing. It is possible to
convert mathematically the reflected sound pulse into a map of the cross-sectional area of
the airway versus the distance from the site of introduction of the pulse.
In 1989, Hilberg et al. (15) performed the first acoustic rhinometric examination and used
similar techniques to evaluate the geometric features of the nasal cavity. In acoustic
rhinometry, a short-duration sound pulse produced by a sound generator is directed into
the nasal airway through a wave tube. As it travels through the airway, the sound pulse is
partially reflected when a change in cross-sectional area is encountered. The transmitted
and reflected signals are recorded with a microphone and digitized with a computer. The
computer performs mathematical analysis of the reflected wave and produces an area-
distance plot (echogram) (Fig. 23.10). The volume of the nasal cavity can be calculated
by means of mathematical integration of contiguous cross-sectional areas. This technique
has been used to evaluate the geometric features of the nasal cavities of healthy persons,
the preoperative and postoperative condition of patients undergoing septoplasty, nasal
airway obstruction among children, and response to medical therapy among patients with
nasal polyposis.

FIGURE 23.10. Method of acoustic rhinometry. The
sound pulse is produced in a wave tube to produce an
acoustic signal. The reflected sound is recorded with a
microphone in the wave tube. The reflected wave is
compared with the incident wave to assess the geometric
features of the airway. For reproducible results, the wave
tube must be coupled to the nostril with an airtight seal
and must not distort the soft tissue of the nares.



Many authors have validated the accuracy of acoustic rhinometry in assessment of the
cross-sectional area of the nasal cavity (16). The original description of acoustic
reflection technique showed that the area distal to severe constriction may not be
accurately estimated. Roithmann et al. (17) showed that supporting the subject's chin with
a nasal adapter that does not invade the nasal cavity but just engages the rim of the nostril
avoids distortion of the anatomic structures in the nose and provides more accurate
results. Care must be taken to ensure an interface seal between nostril and nasal adapter.
Any acoustic leakage causes measurement error.
Characteristics of Rhinograms
Acoustic rhinometric echograms are area-distance plots with peaks and troughs that
represent widening and narrowing of the airway. Adults with subjective normal nasal
patency have a characteristic plot (Fig. 23.11). The initial flat tracing represents the
nosepiece. The next depression (I notch) corresponds with the functional isthmus nasi.
The second trough (C notch), after a small peak, corresponds with the head of the inferior
turbinate. The tracing then slopes upward (climbing W) with small peaks and troughs that
correspond to the posterior nasal cavity and its increasing cross-sectional area.
Echograms must be interpreted in conjunction with the examiner's rhinoscopic findings.

FIGURE 23.11. Typical acoustic rhinogram shows a
rising W pattern with an initial I notch and later C notch.



Examination of a typical acoustic rhinogram shows several characteristics. The region of
maximum narrowing lies within the first 2 cm of the airway. The average distance of the
region of maximum constriction is considered to be 1.73 cm. This corresponds to the
anatomic location of the nasal valve. Vasoconstriction of the nasal mucosa does not
markedly change this region of narrowing. Slightly farther along the airway, at
approximately 2 cm, is another region of narrowing. This region is normally less narrow
than the nasal valve. In a nose with mucosal congestion, however, this region may be
more constricted than the nasal valve. This region responds to vasoconstrictive agents.
The anatomic location of this region is at the piriform aperture at the level of the head of
the inferior turbinate.
Acoustic rhinometry supports rhinometric findings that the flow-limiting segment of the
nose is anterior to the inferior turbinate. Grymer et al. (18) examined 82 patients with
subjective normal nasal patency and compared acoustic rhinometric findings before and
after decongestion with direct measurement of the columellainferior turbinate distance.
Comparison of the echograms with the direct measurements showed that the minimal
cross-sectional area (MCA) is anterior in the nasal cavity within the first 2 cm of the
airway and is localized at the head of the inferior turbinate in some persons and more
anteriorly at the nasal valve in others. In a separate study, Grymer et al. (19) obtained
echograms before and after septoplasty on patients with septal deviation. The size of the
MCA correlated with the subjective severity of nasal obstruction: subjective symptoms of
obstruction with a smaller MCA and no nasal obstruction with a larger MCA. The
subjects who served as controls and those with objectively small and moderate septal
deviation with subjectively normal nasal patency had a mean MCA of 0.7 cm
2

preoperatively. Subjects with the feeling of nearly total obstruction and objectively severe
septal deformity had a mean MCA of 0.3 cm
2
. Postoperative measurements correlated
positively with dissatisfaction. Dissatisfied patients had an average MCA of 0.45 cm
2
.
The satisfied group had an average MCA of 0.74 cm
2
. These results emphasize the three-
dimensional boundaries of the nasal valve and that patients' subjective symptoms are
directly proportional to the degree of obstruction in the anterior nasal cavity. Whether the
obstruction is caused by skeletal or mucosal abnormality, acoustic rhinometry may be
used for accurate quantification of the effects. Acoustic rhinometry can be used to
quantify the mucosal decongestion produced by topical vasoconstrictors (Fig. 23.12).

FIGURE 23.12. Acoustic rhinogram before and after
vasoconstriction produced by application of a topical
vasoconstrictor. The decongested curve shows an
increase in cross-sectional area most apparent in the
region of the nasal turbinates.



Use of Acoustic Rhinograms
The usefulness of acoustic rhinography is not completely defined. The technique appears
to have promise for quantifying the degree and location of narrowing in the anterior
region of the nose. Its advantage over rhinomanometry is that it allows localization of
abnormalities, and this may allow better diagnosis and better determination of appropriate
surgical procedures. The region most easily evaluated with acoustic rhinometry is the
region best evaluated visually. Acoustic rhinometry alone does provide information about
the effect of narrowing on resistance. For this, rhinomanometry is necessary.
No single method of evaluating the nasal airway correlates with pathologic findings and
the patient's subjective symptoms. Nasal endoscopy and imaging studies provide
anatomic display but do not quantify nasal obstruction. Rhinomanometry can be useful in
determining whether a documented intranasal deformity increases nasal resistance and
therefore causes functional disturbance (13). Acoustic rhinometry can be used for
accurate location and quantification of areas of obstruction in the anterior nasal cavity.
This technique provides objective data to assess the need for surgical correction, to
document postsurgical outcome, and to monitor medical therapy for inflammatory nasal
disorders. Because the technique is rapid and noninvasive, it is an ideal method of
evaluating possible nasal airway obstruction in children (20). Acoustic rhinometry does
not replace previous methods of evaluation of the patency of the nasal cavity but provides
objective documentation that is accurate and reproducible.

HIGHLIGHTS
The function of the nasal airways is to warm, humidify, clean,
and regulate the flow of inspired air.
The nasal blood vessels are controlled by sympathetic and
parasympathetic nerves as well as locally released mediators,
which include substance P, histamine, and leukotrienes.
The nasal mucociliary system is essential for the clearance of
mucus, debris, and bacteria from the paranasal sinuses and
nasal airway.
The three functional regions of the nasal airway for regulation
of airflow are the nasal vestibule, the nasal valve, and the nasal
cavum.
The nasal valve is the narrowest and highest-resistance segment
of the nasal airway.
Rhinomanometry is used for quantifying the resistance of the
nasal airway.
A total nasal airway resistance greater than 0.3 Pa/cm
3
per
second usually is symptomatic.
The types of nasal obstruction identified with rhinomanometry
are mucosal obstruction, structural obstruction, and dynamic
airway collapse.
Acoustic rhinometry is a method for measuring nasal airway
dimensions with reflected sound waves.
Acoustic rhinometry can help identify the location of flow-
limiting segments in the nasal airway.
CHAPTER REFERENCES
1. Nishihira S, McCaffrey TV. Reflex control of nasal blood vessels. Otolaryngol Head Neck Surg
1987;96:273277.
2. Baraniuk JN, Silver PB, Kaliner MA, et al. Neuropeptide Y is a vasoconstrictor in human nasal
mucosa. J Appl Physiol 1992;73:18671872.
3. Petersson G, McCaffrey TV, Malm L. Substance P and nasal secretion in dog, rat, and man. Ann
Allergy 1989;62:410414.
4. Ferguson JL, McCaffrey TV, Kern EB, Martin WJd. The effects of sinus bacteria on human
ciliated nasal epithelium in vitro. Otolaryngol Head Neck Surg 1988;98:299304.
5. Cole P. Nasal and oral airflow resistors: site, function, and assessment. Arch Otolaryngol Head
Neck Surg 1992;118:790793.
6. Fregosi RF, Lansing RW. Neural drive to nasal dilator muscles: influence of exercise intensity and
oronasal flow partitioning. J Appl Physiol 1995;79:13301337.
7. Santiago-Diez de Bonilla J, McCaffrey TV, Kern EB. The nasal valve: a rhinomanometric
evaluation of maximum nasal inspiratory flow and pressure curves. Ann Otol Rhinol Laryngol
1986;95:229232.
8. Pallanch JF, McCaffrey TV, Kern EB. Normal nasal resistance. Otolaryngol Head Neck Surg
1985;93:778785.
9. McCaffrey TV, Kern EB. Clinical evaluation of nasal obstruction: a study of 1,000 patients. Arch
Otolaryngol 1979;105:542545.
10. Fisher EW, Liu M, Lund VJ. The nasal cycle after deprivation of airflow: a study of laryngectomy
patients using acoustic rhinometry. Arch Otolaryngol (Stockh) 1994;114:443446.
11. McCaffrey TV, Kern EB. Response of nasal airway resistance to hypercapnia and hypoxia in man.
Ann Otol Rhinol Laryngol 1979;88:247252.
12. Mertz JS, McCaffrey TV, Kern EB. Role of the nasal airway in regulation of airway resistance
during hypercapnia and exercise: second-place resident award at 1982 research forum.
Otolaryngol Head Neck Surg 1984;92:302307.
13. Mertz JS, McCaffrey TV, Kern EB. Objective evaluation of anterior septal surgical reconstruction.
Otolaryngol Head Neck Surg 1984;92:308311.
14. Jackson AC, Butler JP, Millet EJ, et al. Airway geometry by analysis of acoustic pulse response
measurements. J Appl Physiol 1977;43:523536.
15. Hilberg O, Jackson AC, Swift DL, et al. Acoustic rhinometry: evaluation of nasal cavity geometry
by acoustic reflection. J Appl Physiol 1989;66:295303.
16. Mayhew TM, O'Flynn P. Validation of acoustic rhinometry by using the Cavalieri principle to
estimate nasal cavity volume in cadavers. Clin Otolaryngol 1993;18:220225.
17. Roithmann R, Cole P, Chapnik J, et al. Acoustic rhinometry in the evaluation of nasal obstruction.
Laryngoscope 1995;105:275281.
18. Grymer LF, Hilberg O, Pedersen OF, et al. Acoustic rhinometry: values from adults with
subjective normal nasal patency. Rhinology 1991;29:3547.
19. Grymer LF, Hilberg O, Elbrond O, et al. Acoustic rhinometry: evaluation of the nasal cavity with
septal deviations, before and after septoplasty. Laryngoscope 1989;99:11801187.
20. Zavras AI, White GE, Rich A, et al. Acoustic rhinometry in the evaluation of children with nasal
or oral respiration. J Clin Pediatr Dent 1994;18:203210.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

24 NONALLERGIC RHINITIS
Head & Neck SurgeryOtolaryngology
24




NONALLERGIC RHINITIS
SHAWN D. NEWLANDS

S.D. Newlands: Department of Otolaryngology, University of Texas Medical Branch at Galveston,
Galveston, Texas.


Classification
Infectious Rhinitis
Hormonal Rhinitis
Vasomotor Rhinitis
Nonallergic Rhinitis with Eosinophilia Syndrome
Occupational Rhinitis
Drug-induced Rhinitis
Gustatory Rhinitis
Atrophic Rhinitis
Rhinitis among Children
Differential Diagnosis
Allergic Rhinitis
Rhinosinusitis
Anatomic Nasal Obstruction
Systemic Disease
Clinical Evaluation
History
Physical Examination
Special Diagnostic Techniques
Management
Antihistamines
Decongestants
Corticosteroids
Intranasal Cromolyn Sodium
Intranasal Anticholinergics
Chapter References
Rhinitis is inflammation of the mucous membranes lining the nose. The disease is
characterized by nasal congestion, rhinorrhea, sneezing, itching of the nose, postnasal
drainage, or a combination of these symptoms. The disease is grossly classified as
allergic or nonallergic rhinitis. Allergic rhinitis is the most common cause of rhinitis and
is addressed in Chapter 25. Nonallergic rhinitis can be caused by infectious, hormonal,
occupational or other factors. It is estimated that allergic rhinitis affects 20 to 40 million
persons in the United States every year and that even another 20 to 40 million are
affected by nonallergic rhinitis. The burden imposed on society by this seemingly benign
disease is staggering when medical treatments and lost productivity are accounted for. In
1995, the estimated direct and indirect cost of allergic rhinitis was 2.7 billion dollars in
the United States. Rhinitis contributes to associated medical problems, including asthma
and rhinosinusitis (1), which further increase the cost of this disease. Morbidity from
rhinitis includes a deterioration in the patient's quality of life because of headache,
fatigue, cognitive impairment, and side effects of medications. Evidence suggests that the
incidence of rhinitis is on the rise.
An effort has not consistently been made to define the cause of rhinitis for every patient.
Poor understanding of the disease in individual instances can lead to poor control of
symptoms because optimal management varies with etiologic factors (2). This chapter
reviews the classification of nonallergic rhinitis, the differential diagnosis, clinical
evaluation, and treatment. Nonallergic rhinitis is rhinitis not caused by IgE-mediated
immunopathologic events. It can be persistent or intermittent. There are several described
categories of nonallergic rhinitis, and they have distinct symptoms, causes (although
these are not always known), and treatments.
CLASSIFICATION
Infectious Rhinitis
Acute rhinitis usually is caused by a viral infection, a so-called upper respiratory tract
infection. A larger number of viruses have been implicated, including rhinoviruses,
respiratory syncytial virus, parainfluenza virus, influenza virus, and adenoviruses. These
infections cause nasal obstruction, clear rhinorrhea, fever, and sneezing. The edema
caused by the infection can obstruct the ostia to the sinuses, leading to facial pain. The
obstructed sinuses often become superinfected with bacteria, and bacterial rhinosinusitis
results. Although it is a self-limiting disease, the common cold is the source of
considerable societal expense because of lost wages and the cost of treatment.
Hormonal Rhinitis
Causes of hormonal rhinitis include hypothyroidism (myxedema) and elevated estrogen
levels due to pregnancy, use of oral contraceptives, and the menstrual cycle. High levels
of estrogen inhibit acetyl cholinesterase activity and stimulate acetylcholine production in
the parasympathetic ganglia, leading to edema, hypersecretion, and vascular engorgement
of the nasal mucosa. Pregnancy-induced rhinitis occurs in 20% of pregnancies, frequently
with an onset in the second trimester of pregnancy. Swollen, pale, edematous turbinates
characterize this condition. Care should be taken in making this diagnosis, however,
because other causes of rhinitis, including allergic rhinitis, are common causes among
pregnant women. Rhinitis related to hypothyroidism can lead to a diagnosis of that
condition, and other symptoms of hypothyroidism should be sought.
Vasomotor Rhinitis
Vasomotor rhinitis also is called perennial nonallergic rhinitis, idiopathic rhinitis, or
nonallergic rhinitis without eosinophilia (2). Patients have rhinitis that is neither
immunologic nor infectious. Primary symptoms include congestion and rhinorrhea,
usually without sneezing or pruritus. Patients have low nasal eosinophil counts and
negative skin test results for allergy. Vasomotor rhinitis can represent a heterogeneous
group of pathologic conditions. Despite the implication of the name vasomotor rhinitis,
no definitive mechanism has been elucidated (2). One theory is that vasomotor rhinitis is
caused by abnormal functioning of parasympathetic input to the turbinate and septal
mucosa. Parasympathetic input to the turbinates and septum originates in the
hypothalamus and travels with the fifth and seventh cranial nerves. This cholinergic
pathway ends in dilatation of nasal mucosal vessels, which produces a boggy, edematous
mucosa in the lateral nasal wall, septum, and especially the turbinates. For most patients,
rhinitis develops in response to environmental conditions, including cold air, high
humidity, stress, or irritants such as alcohol, bleach, solvents, air pollution, and smoke.
This disease may account for the large number of cigarette smokers who have rhinitis but
are refractory to treatment.
Surgical procedures to correct vasomotor rhinitis are designed to eliminate turbinate
edema and hypersecretion by means of targeting the suspected neurologic source (e.g.,
vidian neurectomy) or the affected mucosa of the inferior or middle turbinates (e.g.,
partial turbinectomy or turbinate ablation). Although vidian neurectomy has been
associated with symptom alleviation, the efficacy of this controversial procedure has not
been proved.
Nonallergic Rhinitis with Eosinophilia Syndrome
Nonallergic rhinitis with eosinophilia syndrome is clinically similar to allergic rhinitis but
lacks the immunoglobulin E (IgE)mediated immunopathologic events. The clinical
syndrome is a perennial course of watery rhinorrhea and nasal pruritus with paroxysms of
sneezing (2). Patients are typically middle-aged, and nasal smears contain eosinophils.
The incidence of this disease is unknown; many cases are diagnosed as allergic rhinitis.
The cause is unknown, although there is evidence of a relation between this disease and
aspirin sensitivity (3).
Occupational Rhinitis
Occupational rhinitis is a diagnosis that overlaps allergic and vasomotor rhinitis. This
syndrome is defined as nasal discharge or congestion due to exposure to an airborne
substance at work. This reaction can be either allergic or nonallergic. Common allergic
triggers in the workplace include laboratory animals, food products, wood dust, and latex.
Common nonallergic irritants encountered in the workplace include cold air, tobacco
smoke, industrial chemicals, and cosmetic products such as perfume and hair spray.
Many patients report worsening of symptoms while at work and improvement away from
work. The symptoms can be chronic or intermittent. Diagnosis of allergic occupational
rhinitis is confirmed by means of skin testing with the suspected allergen. An alternative,
specific test for allergic or nonallergic sources is to challenge the patient with the
suspected irritant or allergen and document a change in symptoms or nasal resistance by
means of rhinomanometry. Although formaldehyde has been suggested as a common
source of occupational rhinitis, the evidence is not conclusive. Management of
occupational rhinitis is identification of the offensive environmental factor and avoidance
of it.
Drug-induced Rhinitis
Drug-induced rhinitis can be caused by systemic drugs that have effects on the nasal
mucosa or by topical drugs. Antihypertensive drugs are the most often implicated
systemic medications. Drugs believed to induce rhinitis include reserpine, guanethidine,
phentolamine, methyldopa, prazosin, chlorpromazine, and drugs in the -blocker and
angiotensin-converting enzyme classes (2). These drugs can cause fairly mild symptoms
of isolated congestion or rhinorrhea or can be part of a complex of symptoms that
includes rhinosinusitis, nasal polyposis, and asthma.
Of the topical drugs, cocaine and over-the-counter nasal decongestants commonly cause
drug-induced rhinitis. Rhinitis medicamentosa is caused by prolonged use of topical
vasoconstricting agents such as cocaine, oxymetazoline hydrochloride, and phenylephrine
hydrochloride, as well as others derived from sympathomimetic amines and imidazoles.
Patients with chronic nasal obstruction due to anatomic abnormalities such as deviated
septum or due to use of medications may be tempted to use these fast-acting topical
sprays or drops for longer than is recommended by the manufacturer, usually 3 days.
Tachyphylaxisthe rapid reduction in drug effect after administration of several doses
may prompt the patient to use vasoconstricting agents for extended periods. This causes
further rebound effects due to down-regulation of nasal mucosal -adrenergic receptors.
Rhinitis medicamentosa is caused by refractory vasodilatation of mucosal blood vessels
or excessive mucosal edema. With prolonged vasoconstriction, mucosal arterioles and
vessels become fatigued and hypoxic, subsequently vasodilating to resupply nutrients to
the highly vascular mucosa. However, as vascular cells vasodilate, they become
increasingly permeable and allow an excessive amount of water to off-load into the
hypertonic nasal mucosa. Mucosal injury, such as loss of cilia, metaplasia, or fibrosis, can
occur as a more serious consequence of prolonged hypoxia owing to the use of
vasoconstrictors. Abuse of cocaine also irritates and inflames the mucosa and can lead to
septal perforation.
Rhinitis medicamentosa can overlie the original pathologic condition for which the
decongestant abuse was started, which can cause a diagnostic dilemma. This diagnosis
must be considered for any patient using the causative medicines for more than 7 days.
One diagnostic technique is to ask patients to show the physician any over-the-counter
sprays they are taking. Patients with rhinitis medicamentosa rarely travel without a spray,
so strong is their reliance on nasal decongestants.
The objective of therapy for rhinitis medicamentosa is to eliminate this secondary
refractory condition so that the primary condition, such as allergic rhinitis, turbinate
hypertrophy, deviated nasal septum, or sinusitis, can be managed effectively. Therapy for
rhinitis medicamentosa begins with cessation of topical administration of a
vasoconstrictor. The physician must explain the importance of this first crucial step to
secure full compliance. Replacement of the vasoconstrictive spray with saline nasal spray
helps both patients with and without allergies. Saline nasal spray mobilizes and loosens
secretions and keeps the recovering mucosa hydrated.
For patients with acute nasal obstruction after nasal spray withdrawal, some physicians
administer a high burst of prednisone with a rapid taper to reduce mucosal edema.
Patients with allergic rhinitis should take a daytime course of oral vasoconstrictors or oral
antihistamines and an oral antihistamine at night. Patients with concurrent allergy may
find additional relief with the use of a corticosteroid nasal spray during the previous oral
regimen. Although corticosteroid sprays or anticholinergic agents provide some
symptomatic relief from rhinitis medicamentosa to persons who do not have allergies,
few studies have been performed to investigate the efficacy of managing rhinitis
medicamentosa with these products.
Gustatory Rhinitis
Ingestion of food can cause rhinitis. There are several known causes of this reaction.
Rhinitis can be caused by food allergy, resulting in IgE-mediated rhinitis. This reaction is
rare, however, without systemic symptoms such as gastrointestinal symptoms,
dermatologic symptoms (urticarial rash, facial swelling), or pulmonary symptoms
(bronchospasm). In such cases, an allergy-mediated reaction is suspected and can be
confirmed with skin testing. Consumption of alcoholic drinks also can cause rhinitis. The
mechanism is believed to be the direct effect of the alcohol in dilating nasal vasculature.
Hot or spicy food can cause profuse watery rhinorrhea through a vagally mediated
mechanism.
Atrophic Rhinitis
Atrophic rhinitis, or rhinitis sicca, is characterized by atrophic mucosa on the septum,
turbinates, or lateral nasal walls. Atrophic rhinitis can be associated with ozena (thick,
foul-smelling, dry crust), although ozena is now more common in developing nations.
Atrophic rhinitis is either primary or secondary. The symptoms are subjective nasal
congestion and a constant foul-smelling odor despite lack of objective evidence of
obstruction. Primary atrophic rhinitis occurs among elderly patients and is more prevalent
in eastern Europe, Egypt, India, and China.
Atrophic rhinitis with ozena manifests as thick, adherent, green or yellow nasal crust that
usually has a bad odor. Without ozena, this condition can be identified by dry, atrophied
mucosa. Patients with atrophic rhinitis with or without ozena typically have some sinus
disease that causes swelling of the ostial mucosa. Some patients with marked crusting
describe nasal obstruction despite having a widely patent nasal cavity. This sensation of
obstruction can be caused by decreased sensation of nasal airflow or an actual decrease in
airflow due to higher levels of turbulent airflow within the nasal cavity. Intranasal crust
may favor formation of turbulent airflow rather than the normal laminar airflow that
occurs along the mucosal surface.
Although histologic findings are varied, mucosa with atrophic rhinitis usually is classified
by the transformation of pseudostratified columnar epithelium into islands of keratinized
squamous epithelium. This keratinized squamous epithelium can be sloughed off in large
sheets from the mucosal surface as the characteristic nasal crust of ozena. Columnar and
goblet cells are nearly absent from the mucosal epithelium, and glandular cells have a
scarcity of secretory vesicles, possibly contributing to the absence of a protective mucous
layer in this tissue. Inflammatory cells and mast cells usually infiltrate the mucosal
lamina propria. Cytologic examination of nasal smears shows high numbers of
neutrophils, bacteria, and metaplastic and squamous cells with few columnar and goblet
cells. The patients have considerable nasal crusting, have atrophy of the nasal mucosa
with squamous metaplasia, and may have atrophy of the bony turbinates, which enlarges
the nasal airway. The disease often causes chronic sinusitis and headaches, confusing the
diagnosis.
The abundance of cases of atrophic rhinitis with ozena in developing nations has led
some physicians to suggest that iron or vitamin A deficiency, as well as poor hygiene,
contributes to the pathogenesis of this condition. The primary form of the disease may be
caused by infection with Klebsiella ozaenae (4). Bacterial strains (K. ozaenae and a toxic
form of Corynebacterium diphtheriae) grow opportunistically in ozena nasal crust and
may have roles in the pathogenesis of atrophic rhinitis. Ciliary beat studies have shown
K. ozaenae to have ciliostatic properties that may facilitate establishment of bacterial
colonies on healthy mucosa. An inherited disability in production of mucus can
contribute to the establishment of ciliostatic bacteria and the development of atrophic
rhinitis. The secondary form of the disease is caused by over-aggressive nasal surgery,
chronic rhinosinusitis, granulomatous disease of the nasal cavity, or radiation by
increasing the airflow and desiccation of the nasal mucosa.
Rhinitis among Children
Rhinitis is a common problem for children. Children 2 to 6 years old have viral rhinitis
about six times a year. Ten percent of children and 20% of adolescents have allergic
rhinitis. Chronic bacterial rhinitis among children can be caused by an immunologic
disorder, cystic fibrosis, or structural defects such as cleft palate. Nasal polyposis in a
child should initiate an evaluation for cystic fibrosis. Purulent unilateral rhinorrhea
suggests the presence of a foreign body. Rhinitis can be caused by gastroesophageal
reflux disease, particularly among premature infants. This condition is managed by
means of thickening feedings, keeping the infant upright during feeding, and not placing
the infant flat after feedings (5). Development of food allergies is more common in
infancy than later in life, but food allergy rarely causes rhinitis in the absence of other
organ system symptoms. Nasal obstruction is more common among children than among
adults because of the incidence of adenoidal hypertrophy.
DIFFERENTIAL DIAGNOSIS
Signs and symptoms of nonallergic rhinitis can be caused by a number of pathologic
conditions.
Allergic Rhinitis
The diagnosis of allergic rhinitis often is suspected on clinical grounds. Classic
symptoms of allergic rhinitis include paroxysms of sneezing, nasal pruritus, nasal
congestion, clear rhinorrhea, and itching of the palate. Allergic rhinitis often is
accompanied by allergic conjunctivitis, malaise, weakness, and fatigue. Twenty percent
of patients have asthma. Other clues to the diagnosis are atopic eczema, a family history
of ectopy, and a temporal relation between exposure to potential allergens and symptoms
(2). Clinically significant positive skin test results or detection of specific IgE serum
antibodies confirm the diagnosis.
Rhinosinusitis
The presence of cloudy, discolored or foul-smelling nasal discharge helps differentiate
rhinosinusitis from other causes of rhinitis (see Chapter 30). Symptoms are acute or
chronic and bilateral or unilateral. Symptoms of chronic rhinosinusitis include, in
decreasing order of frequency, nasal congestion, purulent nasal discharge, post-nasal
discharge with cough, facial pressure or pain, and olfactory changes.
Fungal infection of the lateral nasal wall and paranasal sinuses can be associated with
nasal obstruction. Mucormycosis, which occurs most often among patients with poorly
managed diabetes, is a pale (early) or dark (late) area in the lateral nasal wall. Computed
tomography (CT) of the affected side often shows marked inflammation of the sinus
mucosa or opacification of the sinus. The diagnosis is confirmed by means of identifying
the pathologic organism with methenamine silver staining. Invasive aspergillosis, a
disease caused by Aspergillus fungi and marked by granulomatous lesions in the
paranasal sinuses, can be managed by means of removal of the affected tissue. Although
removal of infected soft tissue often is curative, bony invasion presents the physician
with a more serious situation. These conditions warrant aggressive surgical treatment and
careful follow-up evaluation. Invasive aspergillosis among immunosuppressed patients,
particularly patients who have undergone bone marrow transplantation, is aggressive and
often fatal. Therapy for mucormycosis and invasive aspergillosis is wide surgical
dbridement and tight control of diabetes or reversal of immunosuppression. Good
outcomes are rare without quick control of the predisposing factors.
Anatomic Nasal Obstruction
Congestion, rhinorrhea, and nasal obstruction can be caused by acquired or congenital
deformities of the nasal airway. Among neonates, choanal atresia is a cause of
obstruction. Among older children and some adults, particularly those with human
immunodeficiency virus disease, nasal obstruction can be caused by adenoid
hypertrophy. Obstruction of the airway by septal deflection, turbinate enlargement, nasal
neoplasia, or adenoidal hypertrophy alters nasal airflow and can block the normal
pathway of nasal secretion; the result is irritation and rhinorrhea. Nasal polyposis occurs
among 10% to 15% of patients with allergic rhinitis but is frequent without allergy.
Polyps can be caused by chronic rhinosinusitis or cystic fibrosis or can be a part of
Samter syndrome (asthma, nasal polyposis, and aspirin sensitivity). Polyps cause
invariant nasal obstruction.
Systemic Disease
Unusual causes of nasal obstruction include systemic diseases such as Wegener
granulomatosis, sarcoidosis, and relapsing polychondritis. Rhinitis may be the presenting
problem. Infections that cause granulomatous obstruction of the nasal cavity include
tuberculosis, leprosy, sporotrichosis, blastomycosis, histoplasmosis, and
coccidiomycosis. Rhinoscleroma is caused by Klebsiella rhinoscleromatis.
Rhinoscleroma causes granuloma in the nasal cavity and often affects the larynx (see
Chapter 27).
CLINICAL EVALUATION
History
A carefully obtained history is important in ascertaining the cause of rhinitis. A general
medical history, including medications used, often includes a systemic illness or
condition, such as pregnancy, that can cause rhinitis, or use of medicines, which can
contribute to the problem. A history or family history of immunodeficiency, ciliary
dyskinesia, or cystic fibrosis may explain the rhinitis symptoms. Known Wegener
granulomatosis, sarcoidosis, or relapsing polychondritis also explain the symptoms. A
history of cocaine use and of abuse of over-the-counter nasal spray is sought. A family
history of allergic rhinitis makes this diagnosis likely.
Discussion of the symptoms must include the initial onset of the disease, the frequency of
the symptoms, and the presence of any factors that trigger acute symptoms. Daily,
seasonal, episodic, and perennial symptoms should be differentiated. The onset of allergic
rhinitis usually is before the age of 20 years. Obstruction that is unilateral and fixed in
severity is likely due to anatomic obstruction, whereas daytime congestion indicates
occupational rhinitis. Cyclical nasal obstruction over several hours often is caused by the
natural nasal cycle. Onset of symptoms with relocation implicates environmental factors.
Symptoms with specific activities such as mowing grass or housecleaning suggest
environmental factors. Hyposmia or anosmia is frequently associated with polyposis.
It is not uncommon for patients to describe their symptoms as sinus, and the
otolaryngologist must elicit explicit symptoms, such as congestion and rhinorrhea.
Symptoms of nasal or palatal itching, sneezing, and eye watering must be specifically
sought. The color and odor of the rhinorrhea must be considered. Mucopurulent discharge
is characteristic of primary or secondary rhinosinusitis. Blood-tinged drainage suggests a
neoplasm. The existence of another allergic processes, such as asthma or urticaria, has to
be ascertained, because this is likely to accompany allergic rhinitis.
Questions should include past and present treatment and the results of such treatment.
Rhinitis often is a chronic problem, and adults with these symptoms have often sought
and received treatment elsewhere. For patients with a history of treatment failure,
compliance with the treatment regimen should be discussed. Patients who have not had
success with nasal steroid spray treatment may have used the medicine for only a few
days before discontinuing it before maximal efficacy was obtained. If a patient has
symptoms of allergic rhinitis, a history of previous allergy testing, desensitization, and
avoidance therapies should be discussed.
Physical Examination
All patients with rhinitis need an examination of the head and neck. Initial, general
observation may show allergic shiners (dark discoloration of the skin under the eyes)
and mouth breathing. Chronic mouth breathing from nasal obstruction can cause overbite
and a high, arched palate. Otologic examination shows serous otitis media or retraction of
the tympanic membrane, particularly among patients with allergic rhinitis and allergy-
induced eustachian tube dysfunction or nasopharyngeal obstruction from an early age.
Allergic conjunctivitis is associated with allergic rhinitis.
Nasal examination begins externally. Children with allergic rhinitis often have a
transverse crease across the bridge of the nose caused by the allergic salute (rubbing
the nose upward to relieve itching and wipe away rhinorrhea). Saddle-nose deformity and
collapse of the nasal valve are structural causes of nasal obstruction. Internal examination
of the nose begins with anterior rhinoscopy, which must be performed before nasal
decongestion. Attention is given to the character and color of the nasal mucosa. Boggy,
pale mucosa is typical of allergic rhinitis. Hyperemia is characteristic of infection and
abuse of topical decongestants. The appearance of the mucosa is not a reliable way to
differentiate allergic from nonallergic rhinitis. Submucosal bumpiness and crusting
suggest granulomatous disease. Attention is directed at the character of the nasal
secretions. Watery secretions are indicative of rhinitis, and thick purulent secretions are
indicative of rhinosinusitis. Anterior septal deflection and turbinate hypertrophy are
documented.
The nose is decongested with topical decongestant sprays, generally oxymetazoline or
phenylephrine. Poor response to decongestion can be caused by rhinitis medicamentosa
or hypertrophy of the inferior turbinate bone. Polyps do not respond to decongestants, but
hypertrophied mucosa does respond. After decongestion, examination of the middle
turbinate and posterior nasal cavity often is possible. This examination shows posterior
obstruction or polypoid disease in the middle meatus.
Nasal endoscopy adds valuable information for diagnosis of rhinitis because of the
spectacular lighting and magnification that the tools afford. Both 0-degree and 30-degree
rigid endoscopes are used. In examinations of adults, 4-mm diameter endoscopes are the
most useful because they provide better illumination than 2.7-mm (pediatric) endoscopes.
Rigid nasal endoscopy usually is well tolerated after application of topical anesthetic and
decongestant. Systematic review of the nasal cavity is important. Attention is given to
examination of the inferior meatus, middle meatus, and nasal roof. The middle meatus
and roof often are best seen with a 30-degree endoscope. The orifices of the nasopharynx
and eustachian tubes are inspected. Anatomic abnormalities are easily detected with this
technique.
Special Diagnostic Techniques
Imaging of the nasal cavity and paranasal sinuses rarely is indicated in the evaluation of
uncomplicated rhinitis. However, these studies are indicated to diagnose or evaluate
recurrent acute or chronic rhinosinusitis, to examine a patient who has abnormal findings
at nasal endoscopy, and to evaluate atypical facial pain. For these purposes, CT is the
method of choice. Limited axial CT scans are more informative than are plain sinus
radiographs, and the costs of CT is almost the same as that of radiography. Thin-section
coronal CT details the anatomic features and is necessary for planning and executing
endoscopic sinus surgery for rhinosinusitis.
Rhinomanometry and acoustic rhinometry can be used to document the severity of nasal
obstruction. Rhinomanometry is used to measure the resistance to airflow through the
nose. This test is useful when an objective measure of the nasal resistance is desired.
Such circumstances include documentation of occupational rhinitis with an increase in
nasal resistance at work or in testing the efficacy of an intervention for obstruction, such
as surgery or medical treatment. In acoustic rhinometry reflection of sound energy is used
to map the volume and dimensions of the nasal cavity. At present acoustic rhinometry is
of little clinical use.
Serum IgE and serum eosinophil levels often are measured as a screening test for allergy.
Neither of these tests has exceptional sensitivity or specificity for allergic rhinitis, so the
clinical utility is controversial. Nasal cytologic examination also can be useful in some
clinical settings. High nasal eosinophil counts occur among patients with allergic rhinitis
and those with nonallergic rhinitis with eosinophilia. High neutrophil counts occur among
patients with infectious rhinitis, although some healthy persons have high neutrophil
counts. Abnormalities in ciliary motility can be detected by means of examining
scrapings of the inferior turbinate.
MANAGEMENT
Management of rhinitis hinges on proper diagnosis. Management of allergic rhinitis (see
Chapter 25) depends on avoidance of inciting allergens, on pharmacotherapy, and on
desensitization. The mainstay of therapy for nonallergic rhinitis is pharmacotherapy,
although avoidance of inciting factors is the therapy for drug-induced and gustatory
rhinitis. Cigarette smoking may be a primary cause of rhinitis or may be an additional
irritant that worsens rhinitis from other sources. Smokers have to stop smoking before
chronic rhinitis resolves. Therapy for acute viral rhinitis is largely symptomatic;
antibiotics are not indicated, although other treatments, including zinc (6) and vitamin C,
have proponents. For patients at risk of complications of influenza, particularly the
elderly and patients with chronic pulmonary or cardiac problems, annual influenza
vaccination against the prevalent strains is recommended. The five major classes of
medication commonly used in the management of rhinitis are antihistamines (systemic
and intranasal), decongestants (systemic or intranasal), steroids (systemic or intranasal),
intranasal anticholinergics, and intranasal cromolyn sodium (2).
Antihistamines
Oral antihistamines are effective in reducing the symptoms of itching, sneezing, and
rhinorrhea in allergic rhinitis. Histamine released from mast cells and basophils dilates
blood vessels, increases vascular permeability, and stimulates parasympathetically
mediated glandular secretions. These effects are mediated by the H
1
histamine receptor.
Classic first-generation antihistamines cross the blood-brain barrier and act centrally,
which produces sedation. Use of these drugs causes learning impairment among children
(7) and contributes to automobile deaths due to central nervous system depression and
impairment. Antihistamines also contribute to decreased productivity and work injury (8).
Second-generation H
1
antagonists are nonsedating because they do not enter the central
nervous system. Earlier second-generation drugs, including astemizole and terfenadine
(withdrawn from the U.S. market in 1998), occasionally caused ventricular arrhythmia,
especially when used in excessive doses, in the presence of severe liver disease and in
combination with some macrolide antibiotics (erythromycin, clarithromycin,
troleandomycin) and azole antifungal agents (ketoconazole, itraconazole) (9). The newer
nonsedating antihistamines, such as cetirizine, fexofenadine, and loratadine, are
recommended because they do not cause cardiac disturbances (10). Antihistamines are
first-line therapy for allergic rhinitis among children, although none of the nonsedating
medicines are approved for children younger than 2 years.
Although the aforementioned medicines are first-line therapy for allergic rhinitis, they
have no efficacy in the management of nonallergic rhinitis. Proper diagnosis is essential.
Systemic antihistamines are not effective in managing nasal obstruction, but they are
effective for allergic conjunctivitis. Intranasal antihistamines relieve nasal congestion and
other antihistamine effects, but because of bitter taste, patients often do not tolerate them.
Decongestants
Decongestants are orally (pseudoephedrine, phenylephrine, phenylpropanolamine) or
topically (phenylephrine, oxymetazoline, xylometazoline) administered -adrenergic
agonists. Pseudoephedrine, phenylephrine, and phenylpropanolamine act on the
respiratory mucosa by stimulating the release of noradrenaline from sympathetic nerve
endings and by direct stimulation of -adrenergic receptors in blood vessels with
negligible to slight -receptor (central nervous system) activity. Over-the-counter
derivatives of these oral decongestants can be cost-effective alternative treatments for
nasal congestion as well. They have no effect on the inflammatory cascade and thus do
not alter itching, sneezing, or nasal secretion.
Oral decongestant agents are most efficacious used alone to manage vasomotor rhinitis
and infectious rhinitis. They are used to manage allergic rhinitis in combination with
antihistamines to control nasal congestion (2). Patients with nonallergic rhinitis and
eosinophilia also may respond to combined antihistamine and decongestant therapy (2).
Systemic effects of oral decongestants include high blood pressure, palpitations,
nervousness, irritability, headaches, palpitations, tachycardia, and urinary retention.
These medicines should be avoided by patients who have hypertension, coronary artery
disease, glaucoma, diabetes, urinary retention, or hyperthyroidism. An additional
contraindication to the use of oral decongestants is concurrent use of monoamine oxidase
inhibitors or tricyclic antidepressants. Oral decongestants should not be used in the first
trimester of pregnancy and should not be used by high-level athletes because they are
banned as performance-enhancing drugs. Topical decongestant preparations cause
rebound congestion through down-regulation of -adrenergic receptors, which makes the
nasal blood vessels less sensitive to endogenous and exogenous agonists. These
medicines are limited to short-term use but are helpful in the management of infectious
rhinitis, eustachian tube dysfunction, and acute exacerbations of allergic rhinitis.
Corticosteroids
Nasal steroids are effective in controlling the four major symptoms of allergic rhinitis
congestion, rhinorrhea, itching, and sneezing (11). They also are effective in the
treatment of some patients with nonallergic rhinitis, especially nonallergic rhinitis with
eosinophilia. Nasal steroids are first-line therapy for rhinitis medicamentosa. Nasal
steroids are preferred to systemic steroids because of a better side-effect profile. The
benefit of these preparations is due to the low effective dosage, localized site of action,
and minimal systemic circulation (approximately 2%). All of the currently used nasal
steroids are metabolized rapidly once absorbed systemically, so they do not cause
suppression of the hypothalamic-pituitary-adrenal axis (12).
Steroid nasal sprays used on an as needed basis can be as effective at managing allergen-
induced rhinitis as the steroid sprays used at regular intervals (13). The most common
side effect is septal irritation, which occurs mainly with use of aerosol formulations,
which can be avoided by spraying away from the nasal septum. Unlike the aerosol
versions, aqueous preparations elicit little to no nasal irritation or burning and are well
tolerated by most patients. Symptomatic relief from seasonal and perennial allergic
rhinitis usually is apparent after 2 weeks of daily use. Although the exact mechanism of
nasal steroids not fully understood, one mechanism appears to be inhibition of
inflammation through inhibition of phospholipase A
2
protein that controls the release of
arachidonic acid (the common precursor to inflammatory mediators, such as
prostaglandins and leukotrienes) from membrane phospholipids. Nasal steroids must be
used with caution in the treatment of children, because these agents can have a short-term
adverse effect on growth. There drugs are considered second-line therapy for allergic
rhinitis among children and should be used at the lowest effective dose, although overall
they are considered safe and effective (2). Athletes are permitted to use nasal steroids, but
systemic steroids are banned (2).
Oral corticosteroids are used to reduce edematous nasal mucosa and gain control over
sinonasal polyposis before surgical excision or prolonged therapy with a nasal steroid
spray. Oral administration of corticosteroids should be performed in a high burst with a
rapid tapering of dosage. Prolonged use (more than 2 weeks) of oral steroids can cause
substantial suppression of the hypothalamus, pituitary, and adrenal systems, and may be
contraindicated in the care of patients with diabetes, tuberculosis, pregnancy, peptic
ulcer, renal disease, emotional instability, or hypertension. Use of steroids can hinder
detection of additional symptoms and infectious processes by masking additional sites of
inflammation.
Injection of a corticosteroid, such as methylprednisolone, into the turbinate produces
local antiinflammatory control with reduced systemic effects. This corticosteroid
preparation must be injected slowly and submucosally with a small-gauge needle to avoid
intravascular injection and blindness through retrograde involvement of the ophthalmic
artery. Even with precautions, this procedure can cause cavernous sinus thrombosis and
blindness and is not generally recommended. Topical steroid treatment is effective and
safer.
Intranasal Cromolyn Sodium
Cromolyn sodium inhibits degranulation of mast cells. Thus it is useful in the prevention
of allergic rhinitis when used before exposure to an allergen. This makes it useful in the
management of seasonal allergic rhinitis. Cromolyn sodium can be safely used in
pregnancy and by small children. It is not useful in the management of nonallergic
rhinitis.
Intranasal Anticholinergics
Intranasal anticholinergic agents are poorly absorbed systemically. They are useful in the
management of rhinorrhea caused by increased cholinergic activity. This drug is
particularly useful in the management of parasympathetically mediated rhinitis, such as
gustatory rhinitis and vasomotor rhinitis. Because part of the allergic reaction is
cholinergically mediated, this drug also is useful to control rhinorrhea in allergic rhinitis.
The use of ipratropium bromide is contraindicated in the care of patients who have
narrow-angle glaucoma or who are taking another anticholinergic agent, as in therapy for
prostatic hypertrophy or bladder neck obstruction.

HIGHLIGHTS
Nonallergic rhinitis is a common problem in otolaryngology,
but the precise diagnosis often is elusive.
Pregnancy-induced rhinitis commonly occurs during the second
trimester.
Vasomotor rhinitis is a condition of unknown causation
characterized by congestion and rhinorrhea without sneezing or
pruritus.
Occupational rhinitis is diagnosed when symptoms of
congestion and rhinorrhea occur when the patient enters the
work environment but resolve when the patient leaves that
environment.
Rhinitis medicamentosa most commonly is caused by extended
use of over-the-counter topical decongestants.
Therapy for rhinitis depends on the cause. The diagnosis must
be made before initiation of treatment for the best results.
Antihistamines are efficacious only in the management of
allergic rhinitis.
Oral decongestants are useful in the management of vasomotor,
infectious, and allergic rhinitis.
Nasal corticosteroids are most useful in the management of
allergic rhinitis and nonallergic rhinitis with eosinophilia.
CHAPTER REFERENCES
1. Ross RN. The costs of allergic rhinitis. Am J Manag Care 1996;2:285290.
2. Dykewicz MS, Fineman SF. Diagnosis and management of rhinitis: complete guidelines of the
joint task force on practice parameters in allergy, asthma, and immunology. Ann Allergy Asthma
Immunol 1998;81:478518.
3. Moneret-Vautrin DA, Hsieh V, Wayoff M, et al. Nonallergic rhinitis with eosinophilia syndrome a
precursor of the triad: nasal polyposis, intrinsic asthma and intolerance to aspirin. Ann Allergy
1990;64:513518.
4. Ferguson JL, McCaffrey TV, Kern EB, et al. Effects of Klebsiella ozaenae on ciliary activity in
vitro: implications in the pathogenesis of atrophic rhinitis. Otolaryngol Head Neck Surg
1990;102:207211.
5. Zeigler RS. Allergic and nonallergic rhinitis: classification and pathogenesis, II: non-allergic
rhinitis. Am J Rhinol 1989;3:113139.
6. Mossad SB, Mackin ML, Medendorp SV, et al. Zinc gluconate lozenges for treating the common
cold: a randomized, double-blind, placebo-controlled study. Ann Intern Med 1996;125:8188.
7. Simons FE, Reggin JD, Roberts JR, et al. Benefit/risk ratio of the antihistamines (H1 receptor
antagonists) terfenadine and chlorpheniramine in children. J Pediatr 1994;124:979983.
8. Walsh JK, Muehlback MJ, Schweitzer PE. Simulated assembly line performance following
ingestion of cetirizine or hydroxyzine. Ann Allergy 1992;69:195200.
9. Kemp JP. Antihistamines: is there anything safe to prescribe? Ann Allergy 1992;69:276280.
10. Woosley R, Darrow WR. Analysis of potential adverse drug reactions: a case of mistaken identity.
Am J Cardiol 1994;74:208209.
11. Mygind N, Dahl R, Nielsen LP, et al. Effect of corticosteroids on nasal blockage in rhinitis
measured by objective methods. Allergy 1997;52[Suppl 40]:3944.
12. van As A, Bronsky E, Crossman J, et al. Dose tolerance study of fluticasone propionate aqueous
nasal spray in patients with seasonal allergic rhinitis. Ann Allergy 1991;67:156162.
13. Juniper EF, Guyatt GH, Archer B, Ferrie PJ. Aqueous beclomethasone dipropionate in the
treatment of ragweed pollen-induced rhinitis: further exploration of as needed use. J Allergy
Clin Immunol 1993;92:6672.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

25 ALLERGIC RHINOSINUSITIS
Head & Neck SurgeryOtolaryngology
25




ALLERGIC RHINOSINUSITIS
RICHARD L. MABRY

R.L. Mabry: Department of Otolaryngology, University of Texas Southwestern Medical Center, Dallas,
Texas.


The Allergic Reaction
Diagnosis of Allergy
Signs and Symptoms of Allergic Rhinitis
Adjunctive Tests
Definitive Testing for Atopy
Management of Allergic Rhinitis
Prevention of Symptoms by Avoidance
Environmental Control
First-line Pharmacotherapy
Second-generation and Third-generation Antihistamines
Recognition and Management of Complicating Factors
Glucocorticoids for Control of Severe or Chronic Symptoms
Nasal Glucocorticoid Preparations
Immunotherapy
Disorders Associated with Allergic Rhinosinusitis
Polyps
Sinusitis
Asthma
Otitis Media
Upper Respiratory Infection
Allergic Fungal Sinusitis
Complications of Treatment
Pharmacotherapy
Immunotherapy
Management of Allergic Emergencies
Advances in Allergic Rhinosinusitis
Diagnosis
Treatment
Areas of Controversy and Continuing Investigation
Food Hypersensitivity
Enzyme-potentiated Desensitization
Acknowledgment
Chapter References
Allergy accounts partly or entirely for the chief symptoms of an estimated 50% of new
patients seen in a general otolaryngology practice. Expertise in managing allergic
problems of the upper respiratory tract is of great practical value for otolaryngologists.
THE ALLERGIC REACTION
The immunologic mechanism of the allergic response is discussed in detail in Chapter 8.
The primary reaction involved in nasal allergy is a Gell and Coombs type I immediate
(anaphylactic) hypersensitivity reaction. Allergen-specific immunoglobulin E (IgE),
which is produced after allergen exposure, is bound to mast cells or basophils. This IgE
reacts with its unique allergen to cause mast cell degranulation and release of histamine
and other mediators of inflammation, such as prostaglandins and leukotrienes. The
reaction begins within 2 to 5 minutes of such an antigen-antibody reaction and reaches a
peak after about 15 minutes. A second (late) phase is the result of mediator release from
cells (neutrophils, eosinophils) and occurs about 4 to 6 hours after the acute phase. These
reactions take place under the influence of numerous mediators called cytokines.
Understanding this prototypical allergic reaction and its effect on the upper respiratory
tract allows the practitioner to consider therapeutic measures in light of site and mode of
action for either preventing or alleviating the results of the allergic event (Fig. 25.1).

FIGURE 25.1. Schematic shows allergic reaction and the
sites of action of various therapeutic measures. 1,
avoidance; 2, immunotherapy; 3, cromolyn; 4,
antihistamines; 5, decongestants; 6, glucocorticoids.



DIAGNOSIS OF ALLERGY
Signs and Symptoms of Allergic Rhinitis
The existence of inhalant upper respiratory allergy is suggested by typical historical
factors and physical signs and symptoms. Symptoms of inhalant allergy include itching
of respiratory mucous membranes, sneezing, rhinorrhea, and postnasal drainage, which
causes throat clearing and coughing. The symptoms may be seasonal or perennial, and a
linkage with known exposure to allergens, especially dust and animal danders, often is
noticed. Allergy symptoms can begin at any age, although children rarely have marked
allergies to inhalants before 2 years of age. Symptoms among younger children often are
caused by food hypersensitivity.
Signs of allergic rhinitis can be accompanied by allergy signs noticed during a head and
neck examination. Patients with airway obstruction from nasal allergy often have an
open-mouthed adenoid facies. Itching membranes cause involuntary grimacing,
accompanied by repetitive upward wiping of the tip of the nose with the hand (allergic
salute). This mannerisms ultimately produces a visible transverse crease across the tip of
the nose. Infraorbital tissue congestion manifests as so-called allergic shiners and
puffiness around the eyes. Allergic nasal mucosa appears pale during rhinoscopy, with
clear rhinorrhea in the absence of secondary infection. Polyps may be present, and
although not all polyps are allergic in origin, patients who have nasal polyps should be
evaluated for contributory allergy. In addition to a high-arched palate, which is part of the
nonadenoidal adenoid facies, prominent pharyngeal lymphoid follicles and lateral bands
are common among patients with allergies.
Adjunctive Tests
Although the findings at anterior rhinoscopy often suggest allergic rhinitis, fiberoptic
endoscopy is useful to look for small polyps, which indicate concomitant sinus disease.
For this purpose, computed tomography of the sinuses is helpful in some instances.
Allergic rhinitis is suggested by the presence of eosinophils in stained smears of nasal
secretions. The patient blows the nose into a piece of waxed paper or plastic wrap, or
mucus is obtained from the surface of the inferior turbinate with a cotton-tipped
applicator or specially designed plastic spoon. The mucus is smeared on a slide and
stained with Hansel stain, a mixture of eosin and methylene blue. If more than 25% of the
cells on the slide are eosinophils, allergy is likely. The presence of all cellular elements
can be graded (0 to 4+). The presence of eosinophils, mast cells, and goblet cells
indicates nasal allergy, whereas an abundance of neutrophils and epithelial debris
suggests infection. The clinician must be aware that prolonged use of topical nasal
glucocorticoids can decrease the proportion of eosinophils in nasal smears. A syndrome
of nonallergic rhinitis with eosinophilia, in both the blood and nasal smears, has been
described. Nasal smears can be considered helpful, but they do not provide enough
information for a definitive diagnosis.
Another adjunctive test for allergy is an assay of total IgE. However, because nonatopic
causes such as parasitism can account for an elevated total IgE and a conversely total IgE
may not be elevated when marked atopy for some inhalants is present, measurement of
total IgE as a sole screening test is neither useful nor cost-effective.
Definitive Testing for Atopy
Proof that upper respiratory allergy is present necessitates finding allergen-specific IgE in
the patient (1). This can be done by means of intranasal challenge with a known allergen
and measurement of increased airway resistance with rhinomanometry or assay of the
level of mediator substances in nasal secretions. However, such testing is not practical in
clinical practice. The first useful allergy test consisted of introducing the suspected
allergen under the skin and allowing it to react with IgE bound to mast cells. The
resulting wheal and flare reaction confirmed the presence of allergen-specific atopy.
Early skin tests were conducted by means of abrading or scratching the skin and
introducing antigens. Because such scratch tests were found to be neither sensitive nor
reproducible, they were soon replaced by a prick test. In this test, the skin is pricked
through a drop of antigenic extract with a specially designed needle, and approximately 3
L of extract is introduced into the skin. The wheal and flare reaction is compared with
results of negative (diluent) and positive (histamine) controls. The results are expressed
as 0 to 4+. Because several tests can be performed easily at one sitting with relatively
little discomfort, prick testing is popular for screening.
The prick test is not sensitive enough to show low degrees of atopy. Intradermal tests are
more sensitive and reproducible than prick tests, although slightly more painful and much
more time-consuming. In the intradermal test, small amounts of antigen (0.01 to 0.05
mL) are injected intradermally. Measurement of the wheal that forms provides a
quantitative dimension not found in prick testing (2).
Another variation of the intradermal test is skin end-point titration (often called
intradermal dilutional testing) in which, beginning with a weak and anticipated
nonreacting dilution, progressively stronger antigen concentrations are injected
intradermally until negative results are obtained at the highest concentration tested or
until the point at which progressive positive whealing occurs (end point of titration) is
determined. The end point marks the concentration at which immunotherapy can safely
be initiated. This bioassay of sensitivity for each antigen allows initiation of
immunotherapy at much stronger antigen concentrations than with the conventional
empiric method of progressing from very weak dilutions for all antigens.
In intradermal dilutional testing, the end point is defined by the first wheal that initiates
progressive positive whealing. Intradermal injection of approximately 0.01 mL of any
liquid forms a wheal approximately 4 mm in diameter, which rapidly enlarges by means
of physical spreading to 5 mm. If no further enlargement occurs within 10 to 15 minutes,
the wheal is considered nonreacting. The wheal is considered positive if it enlarges at
least 2 mm beyond a negative whealto 7 mm or more in diameter. Application of the
next stronger antigen concentration should yield a wheal at least 2 mm larger than the
preceding wheal9 mm or more in diameter. The concentration that produces the 7-mm
wheal represents the end-point dilution, whereas the 9-mm wheal is a confirming wheal.
Variants in positive whealing can occur (Fig. 25.2). For example, positive wheals can
grow more than 2 mm, such as wheals of 5, 8, and 11 mm. A plateau can occur in which
there are two positive wheals before a confirming wheal is noticed, such as 5, 7, 7, and 9
mm. The second 7-mm wheal is considered the end point because it initiates progressive
whealing. In some cases, a very large wheal, called a flash response, can follow negative
wheals, such as 5, 5, and 13 mm. In such cases, usually due to cross-reacting foods, such
as recent watermelon ingestion by a patient tested for ragweed, retesting after 24 hours
establishes a clear-cut end point.

FIGURE 25.2. Whealing responses of dilutional
intradermal testing.



Skin tests are the benchmark for confirming the existence of IgE-mediated inhalant
allergy. However, there are disadvantages to skin testing, including discomfort, the risk
of anaphylactic reaction, and the existence of factors affect skin test results (Table 25.1).
Thus other testing methods have been developed.

TABLE 25.1. FACTORS AFFECTING SKIN TEST
RESULTS



Direct measurement of allergen-specific IgE in patient serum has been possible since the
mid 1960s. In these in vitro tests, patient serum is allowed to react with known antigens
contained on a matrix of varying sorts. After washing to remove unreacted components,
the residual allergen-specific IgE complexes on the matrix are incubated with anti-IgE
and a marker. Another washing removes all but the final sandwich of antigenIgE
anti-IgEmarker. The amount of marker present indicates the amount of allergen-specific
IgE in the serum. If the marker is a radioactive substance, the test is called a
radioallergosorbent test (RAST). Other markers such as fluorescing agents are used in
enzyme-linked immunosorbent assay (ELISA) tests. Results usually are expressed as
classes. Higher values represent the presence of greater amounts of IgE. Modification of
the original RAST scoring system by Nalebuff and Fadal (3) has made the test more
sensitive and correlates RAST scores with sensitivity levels obtained by means of
intradermal dilutional testing (4).
In vitro IgE measurements are considered more specific but less sensitive than skin tests.
In vitro tests are easier on the patient, which undergoes one venipuncture rather than
many skin pricks, and carry no risk of systemic anaphylaxis. In vitro testing takes 1
(ELISA) to 3 (RAST) days, unlike skin tests, which take less than 1 hour. Although
intradermal dilutional testing is performed with a bioassay and the same extracts used in
making treatment mixes, treatment packages based on in vitro results must be checked
initially with a limited skin challenge (vial test) before immunotherapy is begun. Table
25.2 outlines appropriate and inappropriate uses of in vitro tests.

TABLE 25.2. IN VITRO TESTS FOR ALLERGY



Dipstick tests for allergy are based on ELISA technology. Preselected antigens on a
dipstick or in a tube system are sequentially incubated with patient serum, anti-IgE, and a
colorimetric marker. These semiquantitative tests are useful for screening; however,
immunotherapy should not be based on the results of these screens without confirmatory
quantitative in vitro or skin tests. The clinician must also consider whether these tests are
more cost-effective or efficient than a properly performed quantitative in vitro assay for a
limited number of antigens.
Because the United States contains an estimated 1,358 species of grass, 1,775 species of
weeds, and 650 species of trees, the selection of antigens seems to be a formidable task.
However, species cross-reactivity and a knowledge of antigens most likely to have
clinical importance in a given region allow testing for only a few representative grasses,
weeds, and trees. For example, either timothy or rye grass cross-reacts well with most
other common grasses except Bermuda grass and Bahia grass. Because Bahia grass
grows only in limited areas of the United States, testing with Bermuda and either timothy
or rye grass suffices in the diagnosis and management of most grass allergies. Likewise,
weed cross-reactivity, such as short ragweed with giant and western ragweed or pigweed
with careless weed, allows limited testing and treatment. Cross-reactivity among trees is
less marked, and these allergies must be treated individually, depending on local
prevalence.
Adding the most important molds plus house dust mite and relevant animal danders
brings the number of inhalant antigens in the basic screening test to about 15. Others can
be added if positive results are obtained at initial skin or in vitro testing, but if test results
for the screening panel are negative, the likelihood of marked inhalant allergy to other
antigens is less than 5%. Table 25.3 shows antigens in a typical screening panel (5).

TABLE 25.3. EXAMPLE OF INITIAL INHALANT
ANTIGEN SELECTION (NORTH TEXAS)



MANAGEMENT OF ALLERGIC RHINITIS
After a working diagnosis of allergic rhinosinusitis is established with a history, physical
examination, and adjunctive tests, a number of agents can be used to manage the
condition. Allergy testingeither in vivo or in vitromust precede immunotherapy.
Such testing also confirms offenders and facilitates more appropriate allergen avoidance.
The management of nasal allergy proceeds in a stepwise manner.
Prevention of Symptoms by Avoidance
The best treatment for allergic rhinosinusitis is avoidance of inciting allergens.
Preventing the allergic response is preferable to attempting to relieve symptoms caused
by mediator substances acting on target organs. Complete avoidance of all allergens
rarely is practical, but a patient with an allergy should practice the best environmental
control possible.
Environmental Control
Animal dander should be completely avoided. However, patients with allergies often are
too attached to their pets to give them up. At least six antigens from saliva, cat hair,
dander, and pelt have been incriminated in cat allergies. Most of these are contained in
cat dander. These small, light particles linger in a carpet for 3 to 6 months or more after
the cat is gone, and they often are carried on clothing, to be found eventually in public
places where no cat is known to have been. If animals to which a patient is sensitive
cannot be avoided, they should at least be kept out of the patient's primary living and
sleeping areas. Reservoirs such as rugs and upholstered furniture should be cleaned
frequently with a high-efficiency particle-arresting (HEPA) filter vacuum.
Dust is ubiquitous. House dust as a unique antigen does not exist. It contains antigens
such as animal dander, mold, cockroach, and house dust mite. The major species of house
dust mite are Dermatophagoides farinae and Dermatophagoides pteronyssinus.
Dermatophagoides microcerus and Euroglypha spp. are a minority with uncertain
clinical significance. The antigen of the dust mite is contained in its dung balls. Dust
mites thrive in moist areas, feeding off the scales from human skin. Application of benzyl
benzoate to carpets and upholstered surfaces followed by vacuum removal effectively
kills mites for variable periods. Tannic acid denatures mite antigen but does not kill dust
mites. No substance currently available performs both functions. Antigens from
cockroach bodies are clinically important. Thorough environmental control is needed to
minimize exposure of a sensitive patient.
Molds are both outdoor and indoor sources of antigen. Outdoor molds are common from
spring until the first hard freeze. They are especially prevalent in compost bins, leaf piles,
flower beds and gardens, and grass clippings. Indoor molds are present all year,
especially in damp, warm environments. Mold often is found in old shoes, luggage,
books, old newspapers, plants, wallpaper and carpet, especially if previously wet,
refrigerator drip pans, shower curtains, and bathroom tile. Houseplants are an important
source of mold, as are dried flowers, and both should be kept out of bedrooms and major
living areas.
Pollen avoidance is almost impossible short of giving up all outside activities. However,
pollen masks help patients during mowing and gardening, and appropriate filtration
systems in heating and air-conditioning systems produce a pollen-free indoor
environment to which the patient can retreat. Besides learning to avoid specific inciting
antigens, a patient with allergic rhinosinusitis should be instructed in measures that
minimize nonspecific irritation of the nasal mucosa. A saline nasal spray should be used
to cleanse the nasal passages. Avoidance of tobacco smoke and irritating fumes should be
emphasized. Proper ambient humidity should be maintained; wintertime nasal dryness is
detrimental to nasal function, whereas humidity higher than 50% allows mold and house
dust mite to flourish.
First-line Pharmacotherapy
Total avoidance of inciting allergens is not practical; therefore medications to relieve
symptoms also must be offered to allergy patients. Several agents for this purpose are
available over the counterfirst-generation antihistamines, decongestants, and cromolyn.
These drugs offer a first line of treatment of patients without the need for a prescription.
Antihistamines compete with histamine for H
1
receptor sites on the target organs during
the allergic response (Fig. 25.1) and are most effective when taken before allergen
exposure. They relieve the wet symptoms of allergy (itching, sneezing, and rhinorrhea)
but have very little decongestant effect. The primary side effects of conventional
antihistamines are sedation, excessive drying, and possibly aggravation of prostatism or
narrow-angle glaucoma. Although some researchers argue the existence of antihistamine
tolerance (tachyphylaxis), clinical observation shows that first-generation antihistamines
can become less effective with prolonged use, necessitating a change to another class of
antihistamine.
Antihistamines often are combined with decongestants to manage allergic rhinitis.
Numerous combinations are available, and the physician is well advised to become
familiar with a manageable number that represent each major antihistamine group and
change preferences as pharmaceutical developments warrant. Decongestants reduce nasal
mucosal edema. The chronic nature of nasal allergy readily leads to nose-drop
habituation and rebound rhinitis. Therefore systemic administration of decongestants is
recommended. Pseudoephedrine, a stereoisomer of ephedrine, usually is administered at
dosages up to a total of 240 mg/d to adults and in proportionally smaller doses for
children. Phenylpropanolamine has pharmacologic properties analogous to those of
ephedrine but with less central nervous system stimulation. Because of a possible causal
relationship to strokes in younger women, phenylpropanolamine has been withdrawn
from common usage. Widely prescribed as a topical nasal decongestant, phenylephrine is
much less effective in oral form and often is combined with another decongestant, the
adult dosage averaging 40 mg/d.
All systemic decongestants exert an -adrenergic effect, which can cause central nervous
system stimulation, hypertension, and similar undesirable effects. Tricyclic
antidepressants and monoamine oxidase (MAO) inhibitors potentiate these effects, which
can persist as long as 14 days after the MAO inhibitor is discontinued. Therefore these
combinations must be administered cautiously. Phenylpropanolamine may be more likely
than the other compounds to elevate blood pressure among patients with labile
hypertension, although all are probably safe for patients with normal blood pressure.
Anorexia is a side effect of phenylpropanolamine, which is the major ingredient in many
over-the-counter diet pills. Therefore patients must be asked about their use of such
preparations before phenylpropanolamine is prescribed, because overdosage has been
associated with convulsions.
Besides antihistamines and decongestants, nonprescription first-line pharmacotherapy of
nasal allergy includes cromolyn nasal spray, which both prevents the allergic event and
modifies the severity of an existing allergic reaction. Cromolyn stabilizes and protects
mast cells from allergen-induced degranulation and prevents both the immediate and late
allergic reaction. This action of preventing an allergic reaction rather than ameliorating
its effects makes cromolyn unique among pharmacotherapeutic agents.
Cromolyn nasal spray prevents or lessens symptoms when applied before an anticipated
allergen exposure. Used on a regular basis during the patient's allergic season, cromolyn
decreases sneezing, rhinorrhea, and nasal pruritus. Nasal cromolyn is delivered with a
pump spray. Treatment begins with one spray in each nostril every 4 hours when the
patient is awake until relief is evident (normally 4 to 7 days but possibly as long as 2
weeks in cases of severe or perennial allergic rhinitis) and is continued at the
maintenance dose that is effective for the expected season or period of exposure.
Additional treatments should precede anticipated allergen exposure.
Because a patent nasal airway is a prerequisite for treatment with cromolyn or any other
topical nasal medication, a decongestant also is often prescribed. The presence of
obstructing polyps calls for the use of measures other than cromolyn. Cromolyn is most
effective in the care of patients with mild to moderate symptoms and may not be effective
for those whose allergic symptoms are severe or perennial.
Second-generation and Third-generation Antihistamines
The first nonsedating antihistamines (terfenadine, astemizole) are relatively lipid
insoluble and cross the blood-brain barrier poorly. These preparations are essentially free
of undesirable anticholinergic effects. However, because they can cause cardiac
arrhythmia when administered in conjunction with drugs using the P-450 metabolic
pathway (6), both have been withdrawn from distribution in the United States. Other new
antihistamines include relatively nonsedating preparations (loratadine, cetirizine), a safer,
nonsedating acid metabolite of terfenadine (fexofenadine), and topical forms
(levocabastine, azelastine). A congener of loratadine is in the investigational stage.
Because of unique drug interactions and properties, the prescribing literature must be
consulted before any new antihistamine is used.
Recognition and Management of Complicating Factors
Despite the contention of many patients to the contrary, not all that makes them sneeze is
an allergen. However, even when a nasal allergy is present, it can be complicated by
other types of rhinitis. Clinicians must constantly assess the clinical status of patients
with rhinitis and adjust therapy accordingly. If a patient with an allergy who has done
well on a regimen has problems without associated allergen overload, the physician
should consider the presence of other types of rhinitis before changing therapy.
The typical patient with vasomotor rhinitis has rhinorrhea as a result of temperature
extremes, eating, stress, or exposure to irritants. Nasal congestion often accompanies this
rhinorrhea and frequently is worse when the patient assumes a recumbent position. Acute
situational stress can cause nasal symptoms that can be mistaken for an allergy. Because
both allergic and vasomotor rhinitis are not uncommon, the two conditions are expected
to coexist among some patients. Besides avoidance of causative factors, therapy for
vasomotor rhinitis is mainly symptomatic.
Nasal and sinus infections can occur among patients with underlying nasal allergy. Such
problems must be recognized not only to institute appropriate antibiotic therapy but also
because infection often alters the patient's response to allergen immunotherapy. It causes
unacceptable local skin reactions to injections. Allergy injections should be deferred until
antibiotics have become effective, especially if the patient is febrile.
Excessive use of decongesting nose drops or sprays can complicate rhinitis and cause
rebound rhinitis. Unless it is determined by asking the patient that this has occurred and
the process is reversed, response to therapy will be inadequate. A number of medications,
especially -adrenergic blocking agents and some antihypertensive agents, can produce
nasal congestion as a side effect. The physician must establish that this has occurred and
withdraw the offending medication for relief.
When a female patient becomes pregnant, nasal congestion can complicate the clinical
signs and symptoms. Numerous causes can account for rhinitis of pregnancy, more
properly called rhinitis during pregnancy. Although therapy for allergic rhinitis during
pregnancy demands careful attention by the physician, the problem can be controlled
without compromising the health of the mother or the fetus. Table 25.4 presents the
principles for managing nasal allergy during pregnancy.

TABLE 25.4. MANAGEMENT OF ALLERGIC
RHINITIS DURING PREGNANCY



Glucocorticoids for Control of Severe or Chronic Symptoms
Glucocorticoids are clearly the most potent agents available to relieve the symptoms of
many types of rhinosinusitis. They often are reserved for instances in which first-line
measures fail, because they present a risk of serious side effects, even when topically
administered. Discussion continues about whether glucocorticoids should replace
antihistamines as a first-line measure in the management of allergy, and the final answer
is yet to be determined.
Glucocorticoids ameliorate the effects of both acute and late-phase allergic reactions (Fig.
25.1) by decreasing capillary permeability, stabilizing lysosomal membranes, blocking
migratory inhibitory factor, inhibiting arachidonic acid metabolism, and probably through
the action of other mechanisms that are not fully understood. Systemic glucocorticoid
administration can be associated with undesirable side effects and consequences. If such
administration is necessary to relieve severe constitutional allergic symptoms, a single
morning dose equivalent to 15 mg of prednisone or less presents the least risk of adrenal
suppression. Treatment with larger doses or treatment for longer than 1 month must be
terminated by means of gradual dosage tapering to allow endogenous cortisol production
to resume. Glucocorticoid supplementation may be needed by these patients if they are
exposed to stress, including surgery, before adrenal recovery occurs.
The rules for the use of glucocorticoids are as follows:
Establish an accurate diagnosis.
Use other, less hazardous measures first. Limit dosage to the smallest effective amount
for the shortest time necessary to relieve symptoms or control the problem.
Use glucocorticoids locally, when possible, to concentrate the therapeutic effect and limit
the likelihood of systemic complications.
Nasal glucocorticoid aerosols have replaced systemic therapy in the management of
severe symptoms of allergic rhinosinusitis. All nasal glucocorticoid preparations can
produce adverse local effects such as candidiasis, nasal irritation, dryness, bleeding,
crusting, and in rare instances septal perforation. Local irritative effects occur most often
after delivery by a propellant but also can follow administration through a pump spray.
Nasal administration of glucocorticoids can have systemic effects, the risk varying with
the preparation, dosage, and duration of therapy. Since 1998 the U.S. Food and Drug
Administration has required labeling of all intranasal glucocorticoids that addresses the
potential effects of these agents on growth velocity among children. Metaanalysis has
shown that although use of an inhaled glucocorticoid can increase the risk of cataracts
among older adults, the risk is not the same with the use of topical nasal glucocorticoids
(7). A systemic effect is most likely in situations in which patients receive larger-than-
recommended doses for prolonged periods or patients receive both intranasal and inhaled
glucocorticoids for rhinitis and asthma.
Only a small fraction of an intranasally administered drug is absorbed at the target site,
although the major fraction is swallowed and undergoes gastrointestinal absorption. The
rapidity and extent of first-pass hepatic metabolism and the degree of direct absorption
from the nose determine the systemic bioavailability of these drugs. This property is
highly variable among available formulations (8). To further confuse the issue,
conflicting data sometimes are available regarding the same drugs. The practitioner
should thoughtfully assess the available data on systemic bioavailability of new nasal
glucocorticoids and use those with the best safety profiles.
To ensure a patent airway necessary to gain proper benefit from nasal glucocorticoid
sprays, concomitant use of a systemic decongestant may be needed. Large polyps and
large septal deviations prevent proper mucosal contact and decrease the effectiveness of
the medication. Patients must be taught to use glucocorticoid nasal sprays regularly
during times of anticipated allergic symptoms (rather than on an as-needed, single-dose
basis) and to stop therapy if side effects such as epistaxis, crusting, or pain occur. Long-
term administration of nasal glucocorticoids requires regular intranasal examinations by
the physician to avert serious consequences such as septal perforation; dosages and
duration should be monitored to avoid systemic side effects.
Nasal Glucocorticoid Preparations
The first nasal glucocorticoid introduced was dexamethasone, which was delivered with a
fluorocarbon propellant and offered rapid onset of action. Dose-related systemic
absorption occurs with this preparation, which has been withdrawn from the market in the
United States.
Beclomethasone is available as a suspension delivered with a propellant and as an
aqueous pump spray preparation. Each puff delivers approximately 42 g of
beclomethasone. The initial dosage is one spray in each nostril four times a day
(suspension), two sprays in each nostril twice a day (aqueous), or two sprays in each
nostril every day (double-strength aqueous), making a total daily dose of 336 g.
Published data indicate no adrenal suppression until a total daily dose of about 1,600 g
is reached. As with all nasal glucocorticoids, after improvement is noticed, dosage should
be reduced to the lowest effective maintenance level. The maintenance dosage must be
continued through the period of anticipated allergic symptoms. Effects can last for
several days after the spray is discontinued.
Flunisolide nasal spray is contained in a polyethylene glycol base and is delivered with a
pump spray. Each spray delivers about 25 g of flunisolide, and the recommended initial
adult dosage is two sprays in each nostril twice a day, making a total daily dose of 200
g. About 50% of intranasally administered flunisolide is changed to a less active
metabolite in the first pass through the liver. Endogenous cortisol production is
suppressed at a flunisolide dosage of 700 g/d.
Triamcinolone is delivered with either a propellant or a pump spray in an initial dosage of
two puffs per nostril every day, for a total dose of 220 g. Doses greater than 3,200 g/d
are needed to cause adrenal suppression. The vehicle of the aqueous form is said to be
thixotropic, meaning it minimizes run-down into the pharynx after usage.
Budesonide is available in two forms delivered as a pressurized spray in an aqueous
form. The metered-dose nasal spray is recommended at a dose of four puffs in each
nostril for a total dose of 256 g. The aqueous spray, at a recommended dose of one
spray in each nostril once a day, delivers a total daily dose of 64 g, which in this form
appears to be clinically equivalent to the higher dose from the metered-dose spray. Dose-
dependent suppression of endogenous cortisol has been reported after administration of
1,024 g budesonide per day.
Fluticasone is a topically active glucocorticoid with poor gastrointestinal absorption and
extensive first-pass hepatic metabolism. It is delivered with a pump spray, two sprays in
each nostril every day, for a dose of 200 mg. No adrenal suppression has been found after
regimens as high as 1,600 mg per day in initial studies. Both budesonide and fluticasone
have been implicated in a small number of studies as producing evidence of systemic
effects (suppression of serum cortisol and changes in peripheral lymphocyte markers and
osteocalcitonin levels) at normal therapeutic doses. Debate continues about the
implications of these studies.
Mometasone furoate is delivered in an aqueous pump spray once daily, providing a total
daily dose of 200 mg. Because of near-total first-pass hepatic metabolism, this
preparation is said to have a systemic bioavailability of less than 1%.
An additional means of administering glucocorticoids to relieve symptoms of allergic
rhinitis while minimizing systemic effects is by means of intraturbinal injection of a
repository form. This procedure was first reported in the medical literature in 1951. Its
use was questioned in the 1960s because of reports of associated vision loss. In 1981, a
thorough review of 10 documented cases indicated that the mechanism involved was
reflex vasospasm or retrograde embolization into the retinal circulation (9). Suggestions
for preventing these events have been widely published (9,10). When the proper
technique is followed, the procedure is safe and effective. Safe intraturbinal
glucocorticoid injection involves the following:
1. Pretreatment of the mucosa with a topical vasoconstrictor
2. Use of a repository glucocorticoid with small particle size, such as triamcinolone
acetonide
3. Placement of the injection just beneath the mucosa of the anterior tip of the
inferior turbinate
4. Gentle injection that avoids undue pressure
After it is determined that an injection is needed, a mixture of 0.5% phenylephrine and
2% lidocaine on cotton pledgets is placed on the mucosa along the anterior portions of
the inferior turbinates. The procedure is explained to the patient both to gain informed
consent and to forestall a vasovagal needle reaction. One milliliter of triamcinolone
acetonide (40 mg) is drawn into a tuberculin syringe fitted with a 1.5-inch, 25-gauge
needle. After removal of the pledgets, 0.5 mL of the glucocorticoid is gently injected just
submucosally into the anterior tip of each inferior turbinate. If properly performed, the
procedure is painless and causes slight white blanching of the mucosa around the
injection site. The most important factor, that of avoiding undue pressure, sometimes
necessitates turning the needle bevel or moving it slightly to facilitate infiltration. After
each injection, a dry cotton pledget is applied momentarily to hold pressure on the
injection site. The patient is warned to expect some blood-streaked nasal mucus. A few
patients have facial flushing the next day. Injections are not repeated until symptoms
return and never administered sooner than 4 to 6 weeks after the previous injection.
Patients who need two or more intraturbinal glucocorticoid injections per year are
candidates for definitive allergic rhinitis treatment (immunotherapy).
Immunotherapy
The only measure that offers a possible cure for allergy is immunotherapy. It should not
be considered a last resort, and the advantages may be evident at any point in the course
of management. Most candidates for allergen immunotherapy meet the following criteria:
They have symptoms not easily controlled with pharmacotherapy.
They are sensitive to allergens that cannot be readily avoided.
They have symptoms that span two or more allergy seasons or are severe.
They are willing to cooperate in a program of immunotherapy.
Immunotherapy involves parenteral administration of antigens identified with appropriate
in vivo or in vitro tests to (theoretically) stimulate formation of allergen-specific IgG-
blocking antibodies, which eventually compete with IgE antibodies for target sites on
mast cells or basophils.
Throughout an average ragweed season, a typical patient is exposed to a total of less than
1 mg of ragweed antigen E. Immunotherapy with ragweed, on the other hand, approaches
levels of 40 to 1,000 mg of antigen per injection. Among experimental animals, chronic
exposure to small antigen doses increased IgE production, whereas large doses of antigen
administered parenterally have been shown to suppress IgE formation and produce IgG
(blocking antibodies). From this, we see that (a) small initial doses of immunotherapy can
and typically do cause an initial increase in IgE, (b) continued therapy at appropriate
doses causes IgE production to decrease and IgG (blocking antibody) production to
increase, (c) parenteral therapy is necessary to deliver high enough doses to stimulate
formation of blocking antibody, and (d) long-term therapy with very low antigen doses
can worsen rather than improve the patient's condition.
In addition to an initial increase followed by a gradual decline in specific IgE levels
coupled with a gradual (dose-dependent) increase in IgG-blocking antibody levels,
immunotherapy produces cellular changes that include decreased reactivity of basophils
and lymphocytes. There are no conclusive data on the exact mechanism of
immunotherapy, although it is postulated that it involves changes in T
H
1 and T
H
2 ratios as
well as effects on cytokines.
Immunotherapy based on skin end-point titration or in vitro methods usually is
administered once or twice a week until symptomatic response occurs. Treatment is
continued weekly for at least 1 year, every other week for another year, and every 2 to 3
weeks for a third year. These are guidelines, and the physician must adjust dosage and
duration of therapy for each patient. If immunotherapy does not produce the expected
benefit, the physician must consider such factors as increased antigen exposure, an
imbalance in the treatment mix, or other antigens for which testing and possible treatment
are needed; inappropriate immunotherapy doses; other triggers such as foods, chemicals,
irritants, or infection; or an incorrect diagnosis of atopy. Immunotherapy should be
prescribed and administered under the supervision of an appropriately trained physician
who is prepared to manage anaphylaxis.
DISORDERS ASSOCIATED WITH ALLERGIC RHINOSINUSITIS
Allergic rhinosinusitis can be complicated by or associated with other processes.
Polyps
Isolated antrochoanal polyps usually are caused by infection. Among those that are not,
about one third are associated with inhalant allergy. Patients with polyps should at least
be screened for allergy. Although pharmacotherapy and immunotherapy may not produce
total resolution of manifest polyps among patients with allergies, treatment begun before
definitive nasal and sinus surgery and continued afterward appears, at least anecdotally,
to make polyp recurrence less likely.
Sinusitis
Most instances of recurrent sinusitis are associated with obstruction of the ostiomeatal
complex from varying causes, including mucosal edema due to allergy. Chronic
hyperplastic rhinosinusitis can be caused by repeated allergic reactions involving these
target organs. A contributory allergic condition must be considered in cases of recurrent
or chronic sinus disease and of surgery after a failed trial of medical management.
Appropriate immunotherapy started before surgery and continued afterward enhances end
results.
Asthma
Improvement in asthma often follows surgery for chronic sinusitis, and a connection
between hyperreactive lower airway disease and allergic rhinosinusitis has been
postulated. Improvement in asthma after pharmacotherapy for allergic rhinosinusitis has
not been conclusively shown. Many patients with nasal allergies also have asthma, and
management of the two disorders requires close cooperation between the specialists
involved.
Otitis Media
Several risk factors appear to be involved in recurrent otitis media and persistent effusion,
including functional eustachian tube obstruction by infection or allergy.
Upper Respiratory Infection
No causal relation between upper respiratory allergy and frequent upper respiratory
infections has been established. Patients find this difficult to believe because the initial
symptoms of rhinovirus infection (sneezing, rhinorrhea, nasal congestion) mimic those of
allergic rhinitis. Any relief from frequent infections after allergy immunotherapy
constitutes a welcome but unpromised benefit.
Allergic Fungal Sinusitis
Although for years administration of fungal immunotherapy to patients with allergic
fungal sinusitis was said to be theoretically contraindicated, this practice has been shown
not to be harmful. It has been shown to prevent recurrence and minimize dependence on
systemic glucocorticoids in the treatment of these patients. This mode of therapy is being
studied and has been validated by more than 5 years' experience (11).
COMPLICATIONS OF TREATMENT
Management of allergic rhinosinusitis can cause complications, some with high risk.
Complications can be caused by pharmacotherapy or by immunotherapy.
Pharmacotherapy
If undesirable effectssuch as sleepiness and overdrying from first-generation
antihistamines, stimulatory effects of systemic decongestants, local and even systemic
effects of nasal glucocorticoidsoccur with drug therapy for nasal allergy, a change in
therapeutic agent normally alleviates the problem. Serious cardiac arrhythmia has
occurred after administration of terfenadine or astemizole with macrolide antibiotics or
systemic antifungal agents. This emphasizes the need for physicians to remain educated
about interactions and side effects of all new and existing drugs.
Immunotherapy
Because immunotherapy for inhalant allergy involves parenteral introduction of a foreign
protein to which the patient possesses allergen-specific IgE (the antibody that triggers the
Gell and Coombs type I anaphylactic reaction), every allergy injection carries risk of
allergic emergency. Although, however, as many as 10 million such injections are given
each year, only about one fatality caused by immunotherapy is reported annually. The
following guidelines can be used to minimize the possibility of such a disastrous
consequence:
Use intradermal titration methods of skin testing to determine a safe starting dose.
Use in vitro tests for labile patients, such as those with severe asthma, and for antigens
that can produce especially severe reactions.
Confirm in vitro results with a vial test on the skin before instituting immunotherapy.
Exercise great care in the preparation and administration of antigenic extracts.
Advance treatment doses carefully and thoughtfully rather than by a set schedule.
Management of Allergic Emergencies
Knowing how to manage anaphylaxis is important for all physicians, even those who do
not administer immunotherapy, because the same steps are involved in the proper
diagnosis and management of reactions caused by drugs such as penicillin and by insect
stings (12). The physician must first differentiate early anaphylaxis from vasovagal
syncope or needle reaction (Table 25.5). If syncope is present, placing the patient in a
recumbent position and administering an ammonia ampule usually suffices, although
oxygen inhalation can afford both physical and psychologic benefit. The use of a flow
sheet helps to speed proper treatment and makes omission of important steps less likely
(Table 25.6). For personnel likely to be involved in assisting with an allergic emergency,
drills and training in cardiopulmonary resuscitation are recommended. Expiration dates
of drugs and availability of properly operating equipment must be checked regularly.

TABLE 25.5. DIFFERENTIATING VASOVAGAL
AND ANAPHYLACTIC RESPONSES



TABLE 25.6. MANAGEMENT OF ALLERGIC
REACTION



More deaths of anaphylaxis are caused by airway obstruction than by cardiovascular
collapse. After the diagnosis is established, help is summoned, and epinephrine, the
mainstay of treatment of anaphylaxis, is administered. The priorities are (a) establishing
and protecting an airway, (b) establishing an intravenous line, and (c) administering more
epinephrine if needed followed by an antihistamine, a glucocorticoid, and possibly an H
2

histamine receptor blocker, all of which further alleviate acute and late symptoms.
Heparin has a high capacity for binding histamine and has been shown to have a life-
preserving effect in animals given lethal doses of histamine releasers, such as polymyxin,
snake venom, or compound 48/80. Slow, intravenous administration of 10,000 U heparin
to a patient with otherwise refractory anaphylaxis is appropriate, although not to the
exclusion of more conventional measures.
Special circumstances dictate alteration in treatment. Patients taking -adrenergic
blockers appear to be at greater risk of allergic reactions of all causes (immunotherapy,
drugs, insect stings). When such reactions are managed with epinephrine, an unopposed
-adrenergic effect can cause extreme hypertension. The physician should not give larger
doses of epinephrine to patients taking -blockers to break through unresponsiveness to
the drug. Instead, epinephrine should be administered with caution and more dependence
placed on other treatment measures. Tricyclic antidepressants and MAO inhibitors also
potentiate the -adrenergic effects of epinephrine. Patients taking these drugs should be
treated cautiously.
ADVANCES IN ALLERGIC RHINOSINUSITIS
Diagnosis
New developments are making the diagnosis of allergic rhinosinusitis easier, but proper
physician judgment remains critical. Although computer-assisted history taking can save
time and ensure that no important questions are omitted, ongoing evaluation of symptoms
and response to treatment is the responsibility of the allergy team. In vitro testing
methods are being improved to provide accurate results rapidly, but a knowledge of skin
test mechanisms and interpretation remains essential.
Treatment
Second- and third-generation antihistamines relieve symptoms without many of the side
effects of older preparations; however, the cost is greater. The role of leukotriene
modifiers in the management of allergic rhinosinusitis is currently under vigorous
investigation, especially in combination with nonsedating antihistamines. A new
emphasis is being placed on topical therapy, including topical antihistamines, allergy-
blocking agents such as human IgE pentapeptide (HEPP), improved topical nonsteroidal
agents such as nedocromil, and new nasal glucocorticoids. The most promising
therapeutic advance under consideration is anti-IgE for systemic administration.
Standardization of extracts used in immunotherapy, so that one allergy unit of any pollen
is biologically equivalent to one allergy unit of dust mite or mold, promises to contribute
to the safety of the procedure. The ability to measure mediator substances in nasal
secretions has provided a giant stride in studies of the allergic reaction and its proper
therapy.
AREAS OF CONTROVERSY AND CONTINUING INVESTIGATION
Food Hypersensitivity
Little disagreement exists that IgE-mediated acute allergic reactions to food occur, such
as hives after eating shrimp. Such acute hypersensitivity is suggested in the history and
confirmed with in vitro specific IgE assay. Skin tests for this type of allergy present a
danger of anaphylaxis. Controversy exists regarding delayed or cyclic food allergy
(which involves mechanisms other than a Gell and Coombs type I reaction) in which
continued ingestion of the offending food partially masks symptoms. Cyclic food allergy
is best diagnosed with a careful analysis of dietary habits and symptom production
followed by a challenge refeeding test in which omission of the suspected food from the
diet for 4 to 7 days relieves symptoms and in which reintroduction causes symptoms to
recur. The diagnosis is further confirmed by means of skin responses to intradermal
testing, but the importance of symptom provocation by skin testing is questionable.
Enzyme-potentiated Desensitization
In enzyme-potentiated desensitization the enzyme -glucuronidase is used to potentiate
the action of small quantities of antigen. Unlike conventional immunotherapy, which
depends on testing to identify specific offenders, enzyme-potentiated desensitization
entails a mixture of antigens empirically chosen from inhalants, foods, and chemicals.
Strict control of diet and antigen exposure during the initial period of therapy is combined
with injections over a few weeks or months. Although investigations have been
conducted in the United States for several years, no results have been published to
substantiate the benefit of this method.
ACKNOWLEDGMENT
Credit for any expertise I have attained in the field of allergy must be shared with my late
wife, Cynthia Mabry, RN, CORLN. She was the backbone of my allergy practice for 20
years, a compassionate nurse, an innovative researcher, a dedicated teacher, and my best
friend. She is sorely missed.

HIGHLIGHTS
The best management of allergic rhinitis is to avoid the
triggering antigen if possible.
The best pharmacotherapy for allergic rhinitis is that which
prevents the allergic event rather than that which controls the
aftereffects.
The safest way to administer glucocorticoids for allergic rhinitis
is topical, to concentrate on effect and lessen systemic effects,
but even this route carries risk.
Immunotherapy offers the only possible means of cure of
inhalant allergy and is indicated in the care of patients
unresponsive to simple pharmacotherapy, those whose
symptoms span more than one season or are severe, and those
willing to cooperate in a program of injections.
Allergy treatment of patients who are candidates for nasal or
sinus surgery is best begun before surgerynot to avoid
surgery but to ensure better results at surgery and in the long
term.
All that sneezes is not allergy.
Patients with negative results of skin tests for appropriate
allergens with potent extracts properly applied are not
candidates for repeat testing with in vitro allergy tests.
Skin test results are positive more often than in vitro test results
for specific allergens. This may represent a greater sensitivity in
the former or greater specificity in the latter.
If management that has been helpful suddenly becomes
ineffective, a change in allergen exposure or a complication
such as infection or rebound rhinitis may have occurred.
Allergic rhinosinusitis occurs often among patients treated in a
general otolaryngology practice. Management should not tax
the capabilities of a properly trained otolaryngologist.
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and prevention. ENT Journal 1995;74:182188.
11. Mabry RL, Marple BF, Folker RJ, et al. Immunotherapy for allergic fungal sinusitis: three years'
experience. Otolaryngol Head Neck Surg 1998;119:648651.
12. Hunsaker DH. Approaches to otolaryngic allergy emergencies. Otolaryngol Clin North Am
2000;31:207219.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

26 NASAL OBSTRUCTION
Head & Neck SurgeryOtolaryngology
26




NASAL OBSTRUCTION
BRUCE W. JAFEK
BRENNAN T. DODSON

B.W. Jafek: Department of Otolaryngology, University of Colorado Hospital, Denver, Colorado.
B.T. Dodson: University of Oklahoma, College of MedicineTulsa, Tulsa, Oklahoma.


Anatomy and Physiology
Innervation of the Nasal Mucosa
Vascularization of Nasal Mucosa
Mathematical Aspects of Nasal Obstruction
Nasal Valve Obstruction
Evaluation and Assessment
History
Physical Examination
Specific Etiologies of Nasal Obstruction
Anatomic Abnormalities
Growths and Neoplasms
Mucosal Disease
Miscellaneous Causes of Nasal Obstruction
Conclusion
Chapter References
ANATOMY AND PHYSIOLOGY
A brief review of nasal anatomy and physiology is integral to understanding the cause of
obstruction. In addition to warming and humidifying inspired air, the nose serves in
olfaction, air filtration, and the detection of microbial invasion (Table 26.1). This
diversity of tasks and functions suggests the need for a sophisticated system; this is
indeed the case. From superior to inferior, the external nose is composed of paired nasal
bones, the upper lateral cartilage, and the lower lateral (alar) cartilage (Fig. 26.1). The
internal nose, or nasal vault, is bisected by the nasal septum, a partition composed of
cartilaginous anterior and bony posterior tissue. The nasal vault is bounded by the nares
and the posterior choanae and laterally by the nasal walls. The lateral nasal wall is
composed of the laminae papyracea of the lacrimal bone, portions of the ethmoid bone,
and the inferior nasal conchae. Composed of thin bone for structural support and covered
in ciliated epithelium for functional support, the inferior, middle, and superior conchae or
turbinates appear as infoldings along the lateral nasal walls (Fig. 26.2).

TABLE 26.1. FUNCTIONS OF THE NOSE



FIGURE 26.1. Anterior view of nose shows
cartilaginous structure.



FIGURE 26.2. Lateral nasal wall and turbinates.



These bony and mucosal infoldings maximize the effective intranasal surface area and
ensure rapid humidification (to 85% to 95% relative humidity or as much as a liter of
water in 24 hours) and radiant heating of inspired air (reaching 31C to 37C before
reaching the pharynx). This efficient air-conditioning system can be adversely affected by
anatomic variations or functional changes that resist airflow and produce partial or
complete nasal obstruction.
Histologic examination shows that the nasal mucosa shifts from stratified squamous
epithelium at the nasal orifice and at the locus of the nasal hairs (vibrissae) to
pseudostratified columnar respiratory (ciliated) epithelium, which lines the rest of the
nasal vault and paranasal sinuses (Fig. 26.3). The respiratory epithelium contains goblet
cells, which produce a protective mucous layer containing salts, glycoproteins,
polysaccharides, and lysozymes to digest bacterial cell walls. The mucous layer can
entrap inspired bacteria or viruses, particulate matter, and toxins. If the mucosa is
functional, mucosal cilia can remove wastes for digestion and excretion (Fig. 26.4). In
addition to goblet and ciliated cells, the nasal cavity contains stromal cells, inflammatory
cells, nerves, blood vessels, arteriovenous anastomoses that detour flow around capillary
beds, and venous sinusoids that maximally contribute to turbinate hypertrophy and nasal
obstruction. Chemical or microbial perturbation of this sophisticated histologic network
can elicit a rapid release of histamine through direct stimulation or through an antigen
and immunoglobulin Emediated pathway, as in allergic rhinitis, that involves histamine
release from mast cells, basophils, and other leukocytes. Thickening of the epithelium or
engorgement of the stroma on the lateral walls, particularly along the inferior or middle
turbinates, may produce obstruction.

FIGURE 26.3. Low-power (5,300 original
magnification) transmission electron micrograph view of
the respiratory epithelium. Goblet cells (g), ciliated cells
(c), an intermediate cell (l), and several basal cells (b) are
resting on the well-formed basement membrane (bm).



FIGURE 26.4. Low-power (4,750 original
magnification) scanning electron photomicrograph of
human respiratory epithelium. A red cell (5 to 7 mm in
diameter) (r) is in the center of the field. A goblet cell
(g3) is discharging mucus at the upper left, and several
microvillous resting goblet cells (m) and ciliated
respiratory cells (c3) occupy the rest of the field.



Innervation of the Nasal Mucosa
Nasal innervation is composed of sensory, parasympathetic, and sympathetic components
(Fig. 26.5, Fig. 26.6). The olfactory (first cranial) nerve and the first and second division
of the trigeminal (fifth cranial) nerve supply sensory innervation to the nose. The
autonomic nervous system supplies both parasympathetic and sympathetic fibers, which
regulate the degree of vascular tone, turbinate congestion, and nasal secretions.
Presynaptic parasympathetic fibers travel along the facial nerve as far as the geniculate
ganglion and continue in the greater superficial petrosal nerve before joining the deep
petrosal nerve to form the vidian nerve. The fibers travel with the vidian nerve to the
sphenopalatine ganglion, where they synapse with the postganglionic neurons, which
innervate the nasal mucosa. Postsynaptic sympathetic fibers pass through the
sphenopalatine ganglion before terminating in the nasal mucosa. Fibers from the
trigeminal nerve also pass through the sphenopalatine ganglion and transmit sensations of
pain, temperature, and touch.

FIGURE 26.5. Nerve supply of the lateral nasal wall.



FIGURE 26.6. Nerve supply of the nasal septum.



The location of olfactory neuroepithelium varies among individuals, and the
neuroepithelium may shrink with increasing age. Olfactory neuroepithelium is generally
situated on the roof of the nasal vault at the cribriform plate, superolateral aspects of the
septum, and medial surfaces of the superior turbinates. Neuroepithelium can be a
composite region (1 to 4 cm
2
) with interspersed patches of respiratory epithelium. This
specialized epithelium usually is thicker (approximately 200 mm) than respiratory
epithelium (approximately 70 mm), and although it contains cilia, the cilia lack dynein
arms and functional ciliary beat. Excess particles overlying the olfactory neuroepithelium
are removed by the ciliary beat from adjacent functional respiratory epithelia. That is,
nearby cilia mobilize the mucous sheet with its entrapped particles away from the
olfactory neuroepithelium.
Sensory innervation is responsible for olfaction and reflexes that elicit sneezing,
laryngeal constriction, bronchoconstriction, and cardiovascular responses.
Parasympathetic and sympathetic stimulation of nasal mucosa results in direct alterations
of nasal flow. Parasympathetic innervation affects the nasal mucosa primarily through
vasodilator or secretomotor activity leading to obstruction, whereas sympathetic
innervation is primarily vasoconstrictive, which decongests the nose. Relative to nasal
obstruction, parasympathetic and sympathetic effects can dramatically alter the function
of the nasal mucosa.
Specific to nasal flow, nervous reflexive airflow monitoring is most sensitive at the nasal
vestibule, where tactile hair (associated with the vibrissae), Iggo dome, Pacinian, and
Meissner receptors abound (1). Afferent impulses transmitted via the trigeminal (fifth
cranial) nerve allow assessment of nasal airflow from tactile, thermal, and possibly
chemical sensation (1). Interpretation of these sensory data allows perturbation of the
nasal passage through changes in mucosal hypertrophy. In healthy persons, regulation by
the nasal valve, which is just posterior to the alar cartilages, is most apparent at high air
velocity.
Vascularization of Nasal Mucosa
The arterial blood supply to the nasal passage originates from maxillary and facial
branches of the external carotid artery and from the ophthalmic branch of the internal
carotid artery. The ophthalmic branch gives rise to the ethmoid arteries (Fig. 26.7). The
anterior facial vein, the sphenopalatine vein, and the ethmoid vein supply venous
drainage of the nose. The sphenopalatine and ethmoid veins drain into the cavernous
sinus.

FIGURE 26.7. Arteries of the lateral nasal wall.



Nasal mucosa contains a complex array of arteries, arteriovenous anastomoses, and
unique muscular veins and venous sinusoids. The muscular veins and sinusoids can
become engorged or constricted according to the extent of vasodilation or
vasoconstriction in the veins and arteriovenous anastomoses. Vasoconstriction reduces
the volume and retention of arterial blood in the nasal blood vessels and increases the
patency of the nasal passage. Vasodilation increases the volume and amount of blood
retention in the nasal blood vessels, decreases nasal patency, and increases nasal airflow
resistance. Dilatation and subsequent engorgement of the capillary or venous sinusoid
systems can cause nasal congestion.
Mathematical Aspects of Nasal Obstruction
Poiseuille's law is used to characterize the physical relations at work in nasal obstruction,
as follows:

[1]
where nasal airflow rate in milliliters per second (Q) is directly proportional to the change
(decrease) in pressure (P) and the radius of the nasal passage (r) to the fourth power.
Nasal airflow rate (Q) is inversely proportional to the coefficient of fluid viscosity ()
and the length of nasal passage (L). This formula applies only to laminar (uniform)
airflow. Turbulent (disordered) airflow occurs when nasal airflow rate (Q) exceeds 2,000
mL/s, nasal passages have characteristics contributing to formation of turbulent flow,
such as the Reynolds number, or an impingement or defect diverts normal nasal flow.
Turbulent flow occurs according to the following equation:

[2]
where R
e
, the Reynolds number (an empirical measure of the chance of turbulence), is
directly proportional to the diameter of the nasal passage (2r), flow rate (Q), and fluid
(air) density () and is inversely proportional to the coefficient of viscosity (). Laminar
flow occurs at R
e
values less than 2,000, where turbulent flow is more probable at R
e

values greater than 2,000.
Under the conditions of laminar flow, such as when R
e
is less than 2,000 or at a low nasal
flow rate, nasal airflow resistance (R
N
) is a function of the individual nasal passage and
does not depend on the airflow rate (Q), such that

[3]
where the change in pressure (P) is the change in pressure between the air pressure in
the nasal vestibule and the air pressure in the nasopharynx.
Under the conditions of turbulent flow, such as when R
e
is greater than 2,000, there is a
high nasal flow rate, or when a physical obstruction occludes or disrupts nasal flow, nasal
airflow resistance can be expressed with the equation

[4a]
or

[4b]
where

and C
1
and C
2
are empirically determined constants for an individual airway.
An approximation of the total resistance (R
T
) for a nasal passage can be determined from
individual resistances of the right and left nasal passages (R
L
and R
R
), such that

[5]
or

In a review of these formulas, one can see that the most important single variable in nasal
airflow, and therefore in nasal obstruction, is the radius of the nasal passage. In equation
1, nasal airflow is directly proportional to r
4
, or the radius of the nasal passage to the
fourth power. Nasal obstruction can be felt not only as an actual diminishing of the nasal
radius but also as a feeling of obstruction even when the nasal passage shows no
anatomic obstruction. This condition can be caused by sensory input indicating low flow
through the vestibule region due to excessive intranasal turbulence or impingement in the
nasal passage. However, with a high flow rate (Q > 2,000 mL/s) or impingement in
proper airflow, as by a deviated septum, nasal airflow has a higher intensity of turbulent
(obstructive) airflow. Turbulent flow can prevent proper clearance of air volume during
inspiration or expiration and can elicit a feeling of obstruction even when the passage is
visually patent.
The mathematical models tend to oversimplify the true dynamic nature of nasal
obstruction. Continual variation in the characteristics of nasal patency or obstruction is
the rule. Even large-scale models of the nasal passage suggest nasal airflow only
approaches disturbed laminar flow at the lowest flow rates (approximately 167 mL/s),
turbulent flow occurring at medium (approximately 560 mL/s) and high flow rates
(approximately 1,100 mL/s) (2). Unlike flow in large-scale models, laminar flow in the
human nose occurs within only 0.25 mm of the nasal wall. Increasingly turbulent airflow
occurs outside this laminar airflow sublayer at high rates of flow. In addition to a
complex laminar-turbulent cross-section, air humidity and fluctuating airflow velocities
further complicate mathematical models of the nasal passage. With rhinomanometry,
however, it is possible to clinically quantify nasal pressure and flow rates. In conjunction
with rhinomanometry, acoustic rhinometry can help characterize the dimensions of the
obstructed nasal passage. These techniques have been used to quantify the ambiguous
diagnosis of nasal obstruction in evaluations of indications for and postoperative results
of septorhinoplasty, experimental alteration of the physical and chemical properties of
inspired air, and surgical outcomes from functional septoplasty and septoplasty with
inferior turbinectomy.
In addition to structural alterations that increase nasal resistance and turbulent airflow,
normal physiologic alterations, such as those of the so-called nasal cycle, can cyclically
alter the degree of mucosal constriction or dilation. This process, present in
approximately 80% of the population, increases the percentage of inspired air in laminar
flow.
Nasal Valve Obstruction
The radius of the nasal passage is most compromised at the nasal valve, a cross-sectional
area bounded medially by the septum and bilaterally by the junction of the distal section
of the upper lateral cartilage and proximal section of the lateral crura of the greater alar
cartilage (Fig. 26.8). This narrowed area has a floodgate effect on inspiratory and
expiratory airflow and maintains median airflow through flow resistance. Patients with
mesorrhine or leptorrhine characteristics often are susceptible to nasal valve collapse due
to insufficient anatomic support. Iatrogenic factors in rhinoplasty, such as excessive
resection of cartilage from the nasal valve support region, may weaken the nasal valve
and allow it to collapse with maximal inspiration.

FIGURE 26.8. Nasal valve. Cross-sectional plane
crosses the distal upper lateral cartilages, the proximal
extent of the lower alar cartilages, and the anterior head
of the inferior turbinates.



EVALUATION AND ASSESSMENT
Evaluation of nasal obstruction begins with a history and physical examination. Because
the cause of nasal obstruction can be highly variable, the otolaryngologist must be
familiar with the various manifestations to ensure an accurate differential diagnosis.
History
In evaluating nasal obstruction in a patient's history, the clinician must pay particular
attention to the time of onset, duration of symptoms, recourse the patient has taken to
alleviate symptoms, whether the obstruction is unilateral or bilateral, duration of the
obstruction (recurrent or chronic), and contributing factors in the patient's environment. A
complete history also includes a history of rhinorrhea, if any, that includes characteristics
such as purulence, odor, and color; history of epistaxis or blood in nasal secretions;
history of nasal pain; history of symptoms or pain relating to the orbits; history of middle
ear disease or symptoms relating to the middle ear; history of respiratory illness, such as
chronic obstructive pulmonary disease or asthma; history of drug, alcohol, or tobacco
use; history of nasal surgery or trauma; and current use of medications, especially nasal
corticosteroids, aspirin, or other medications that alleviate or exacerbate symptoms of
nasal obstruction.
Most patients with nasal obstruction, describe generalized stuffiness; however, nasal
obstruction can have more obscure, nonnasal manifestations. Common nonnasal
manifestations of obstruction include dry mouth, chronic sore throat, frontal, cheek, or
orbital pain indicating acute or chronic sinusitis, localized facial pressure indicating
sinusitis, excessive snoring, halitosis, parental concern about a child's lethargy or
disinterest, inability to sleep soundly that results in hypersomnolence during the day, and
decreased sense of taste or smell (Table 26.2).

TABLE 26.2. COMMON NONNASAL SYMPTOMS
CAUSED BY NASAL DISEASE



Physical Examination
A physical examination of the head and neck specific to nasal obstruction begins with
evaluation of the external nose. This examination is focused on the size and shape of the
nose. The presence of any deformity or deviation that displaces laterally or depresses
posteriorly the nasal midline is documented. Bony fractures can depress the nasal vault
and narrow the radius of the nasal passage. Trauma to the distal upper lateral nasal
cartilage (the upper lateral wings of the quadrilateral cartilage of the nasal septum) can
dislocate these cartilages and involve the nasal septum intranasally. Congenital anatomic
variation can manifest as thin, weak upper lateral cartilaginous support and an
incompetent nasal valve. These patients can feel immediate restoration of nasal patency
by bilaterally widening the alae with the index finger and thumb (Cottle maneuver). The
appearance of a nasal crease on the nasal dorsum suggests frequent nose wiping and
upward movement of the nose from chronic or allergic rhinorrhea. Depression of the tip
of the nose suggests insufficiency of the lateral alar cartilage, which causes greater
obstruction owing to nasal valve narrowing.
Pressing or percussing the area of the cheeks just lateral to the middle of the nose, just
inferior to the supraorbital tori, and at the base of the nasal bones can reveal tenderness or
pain associated with acute or chronic sinusitis of the maxillary, frontal, or ethmoidal
cavities, respectively. Transillumination of the sinuses is not extremely helpful. Sinus
disease can be localized in recesses of the maxillary or frontal sinuses that cannot be
adequately transilluminated.
Specific associative examinations of the eyes for ptosis, chemosis, proptosis, extraocular
muscle abnormalities, and changes in the ocular fundi are performed to assess the extent
to which an obstructive nasal abnormality transmits into the orbit. In all areas of the head
and neck examination, a specific examination should be based on the abnormal physical
examination findings and on the history and presenting signs and symptoms complaints.
Diplopia is one such indication.
If there is no vasoconstriction, anterior rhinoscopic examination should be performed
through the nares. This can be accomplished with a nasal speculum and head mirror.
Posterior rhinoscopic examination of the nasopharynx, larynx, and posterior choanae is
accomplished through the oral cavity with a head mirror for illumination and a
nasopharyngeal mirror for visualization. During anterior rhinoscopy, the examiner
documents the characteristics of rhinorrhea, septal deviation, or septal spurs and the
extent to which the nasal mucosa is edematous and obstructive. During posterior
rhinoscopic examination, the examiner documents the presence or absence of eustachian
tube patency, hypertrophic adenoid tissue, and abnormal epithelial lesions. In both
examinations, a rigid or flexible fiberoptic nasopharyngoscope can provide superior
illumination with magnification and aid in the identification of pathologic conditions of
the nasal or nasopharyngeal space. Anterior rhinoscopy is repeated after topical
decongestion. Obstruction that resolves with decongestion is caused by mucosal
abnormality.
Purulent secretions can be sampled and sent to the pathology laboratory for anaerobic and
aerobic bacterial cultures when sinusitis is suspected. Cultures from the nasal cavity are
likely to be contaminated by normal respiratory flora. Endoscopically guided swabs of
the sinus ostia are more likely to reveal pathogens than are cultures from the nasal cavity
itself, but it is difficult to obtain these cultures without contamination. Antral aspiration
or lavage is the standard or reference for sinus culture. In the care of patients with chronic
sinusitis unresponsive to antibiotics, it is imperative that bacterial cultures be tested for
antibiotic sensitivity to construct a proper scheme of management. In the care of patients
who have had trauma to the nose or have recently undergone nasal surgery, the
possibility of cerebrospinal fluid (CSF) leakage must be considered.
2
-Transferrin assay
is the most accurate laboratory test to diagnose CSF rhinorrhea. Newer technologies, such
as the electronic nose may enable rapid, accurate detection of CSF rhinorrhea (3).
Nasal discharge can be evaluated for neutrophil content (high content suggests infection),
eosinophil content (high content suggests allergy), and mast cell content (high content
suggests food allergy), although the usefulness of these examinations is questioned. Skin
prick tests can show additional allergic components. Additional laboratory tests include
fungal cultures of suspicious material (white streaking emanating from a sinus ostium or
a localized mass of whitish material within a sinus), skin tests for systemic fungal or
tubercular infection, complete blood cell count with differential, erythrocyte
sedimentation rate, blood calcium level to rule out sarcosis (high calcium level), and
serologic tests for syphilis.
Radiologic screening can provide vital information when inflammatory disease, sinusitis,
trauma, neoplastic growth, or congenital abnormality is suspected (see Chapter 29).
Biopsy is indicated when a neoplasm or an unusual inflammatory process, such as fungal
infection or Wegener granulomatosis, is indicated.
SPECIFIC ETIOLOGIES OF NASAL OBSTRUCTION
The most common diagnoses of nasal obstruction are presented in Table 26.3. Strategies
for the management of nasal obstruction are based primarily on the history, physical
examination findings, and results of laboratory tests, where applicable. More involved
diagnostic studies, such as biopsy or computed tomography (CT) of the sinuses, can be
used to confirm the original diagnosis and help plan treatment, such as the extent of
surgical excision. They also help define the anatomic and pathologic characteristics of the
paranasal sinuses. Alternative diagnoses must be kept as contingencies in the event of
treatment failure.

TABLE 26.3. DIAGNOSIS NASAL
OBSTRUCTION WITH COMMON CAUSES



Management of nasal obstruction can be divided into three general areas: medical
intervention, surgical intervention, and a broad other category. In executing a treatment
plan, the physician must remember the simplest explanation or treatment strategy is the
correct first approach to nasal obstruction for the patient at hand. The physician should
consider management of nasal obstruction a span of treatments, including no treatment or
a minimally invasive approach, such as removal of the irritant or observation; medical
management, such as oral decongestants, oral antihistamines, corticosteroid nasal spray,
intraturbinal steroid injection, antibiotics, topical ointments; and surgical procedures,
such as septoplasty, nasal valve repair or augmentation, submucous resection or ablation
of the nasal turbinates, and resection or removal of any neoplasms or obstructive
anatomic structures. The most common therapies for nasal obstruction are shown in
Table 26.4.

TABLE 26.4. TREATMENT NASAL
OBSTRUCTION



Obstructive anatomic features, such as a deviated septum or neoplasm, are treated
primarily with surgery, whereas obstructive abnormalities that cause nasal obstruction,
such as turbinate mucosa hypertrophy, are managed surgically only after failure of
aggressive medical treatment. Surgical management of nasal obstruction usually includes
procedures on the septum (submucous resection or septoplasty), septum and outer
cartilaginous support of the nose (septorhinoplasty through the internal or more
commonly the external approach), turbinate bones (submucous resection or partial
turbinectomy), turbinate mucosa (mucosal ablation by means of electrocautery, laser, or
cryotherapy), or neoplastic tissue (surgical debulking and removal).
Anatomic Abnormalities
Common anatomic abnormalities that cause nasal obstruction include septal deviation,
turbinate hypertrophy, septal perforation, and nasal valve collapse. A less common
obstructive condition is congenital choanal atresia.
Deviated Nasal Septum
Deviated septum is the most common cause of nasal obstruction. Among patients with
nasal septal deviation, a history of nasal or midfacial trauma often indicates the original
alteration of normal nasal anatomic features. Improper forceps placement or birth through
an unusually narrow pelvic canal can cause septal deviation early in anatomic
development. Trauma can displace anatomic features externally, such as nasal bones or
upper lateral cartilage, internally, or as a combination of external and internal alterations.
Internal deviation can be caused by singular or concerted alteration of the bony portion or
cartilaginous portion of the septum; however, bony alteration of the posterior septum (the
vomer or perpendicular plate of the ethmoid) is less frequent. Patients with unilateral
septal deviation most often have nasal obstruction of the contralateral side.
Nasal turbinate bone hypertrophy can be caused by a lack of structural resistance by the
nasal septum. Turbinate mucosal hypertrophy occurs as a reaction to external stimuli,
such as allergens, or in the nasal cycle when atrophy alternates between the right and left
nasal passages in a cyclic manner. When the nasal septum is deviated, mucosal swelling
on the contralateral side does not have proper resistance to growth. This mucosa can
swell unabated, whereas the ipsilateral side is hypotrophic. Normal hypertrophic mucosa
encounters the nasal septum and shrinks to reestablish nasal patency. Many patients with
nasal septal deviation have a history of recurrent sinusitis. Because of the existence of
hypertrophic mucosa, a patient with a deviated septum also can have a history of chronic
sinusitis. Chronic sinusitis as a secondary condition can be caused by unilateral or
bilateral impingement of the nasal passage. Impingement reduces nasal airflow through
turbulent resistance and can induce thickening, atrophic mucosal changes, or crusting of
the nasal mucosa. These changes can block the sinus ostia and proper sinus drainage on
the contralateral or ipsilateral side. For this reason, septoplasty often is combined with
concurrent functional endoscopic surgical procedures on the sinus, submucous resection
of the inferior or middle turbinates, or rhinoplasty.
Medical treatment centers on the use of aerosol or aqueous steroid nasal spray.
Antihistamines can be used if coincident allergic rhinitis is suspected. Use of
decongestant sprays should be avoided because anatomic nasal obstruction is a chronic
problem, and use of these medicines risks development of rhinitis medicamentosa.
Medical management may not provide relief to patients with hypertrophic turbinates due
to septal deviation. These patients need surgical treatment.
Septoplasty alleviates nasal obstruction by means of surgical resection of impinging
anterior cartilaginous or posterior osseous septal deviation. The clinical indications for
nasal septal surgery can serve as a helpful guideline for the surgical management of this
condition (Table 26.5). Nasal septal surgery involves conservative resection of the
septum. The surgeon resects only the deviated portion of the septum, allowing maximal
preservation of this important structural component of the nose. The nasal septum
provides structural support to the nasal dorsum and a medial boundary to turbinate
enlargement. Critical to successful outcome in septal surgery is thorough preoperative
evaluation that identifies the areas where the symptoms arise.

TABLE 26.5. STANDARD ENVIRONMENTAL
CONTROL MEASURES



Septoplasty is performed with local or general anesthetic. The latter is preferred for
operations on patients who are apprehensive about surgery or when transnasal surgery is
anticipated. Subperichondrial injection of hemostatic solution such as lidocaine 1% with
1:200,000 epinephrine is critical to hemostasis. Placement of the incision depends on the
specific area of the septum that needs to be addressed. If the caudal quadrangular
cartilage is dislocated from the anterior nasal spine, a hemitransfixion incision is
preferred for access to this area. This incision passes through the membranous septum
between the medial crura of the lower lateral cartilages and the caudal quadrangular
cartilage.
When obstruction involves the posterior cartilaginous septum or the bony septum, a
Killian incision (vertical incision about 1 to 2 cm from the columella) is preferred. After
the incision is made, a mucoperichondrial-mucoperiosteal flap is raised in the
subperichondrial-subperiosteal plane on the side of the incision. Before any cartilage or
bone is removed, the mucoperichondrium-mucoperiosteum on the contralateral side is
also raised. Access to the contralateral side is either through the septum or around the
caudal septum, depending on the exposure. Deviated portions of the septum are identified
and removed. The classic submucosal resection involves removal of the septum except
for a 1-cm wide dorsal and caudal strut that remains for nasal support. Conservation
resection usually is adequate. Septal spurs due to overgrowth of the maxillary crest can
be removed with an osteotome. Resection of the bony septum is accomplished with
Jansen-Middleton rongeurs. Care is taken not to rock the perpendicular plate of the
ethmoid bone. Rocking can cause cerebrospinal rhinorrhea through a fracture of the
cribriform plate. Care also is taken to avoid tearing the septal flaps, because bilateral tears
can cause septal perforation.
When deviation involves the dorsal strut of the septum, removal of the deviated portion
followed by reconstruction with straight cartilage grafts may be needed to straighten the
septum and avoid loss of nasal tip support. As much cartilage as can be conserved should
be conserved. The surgeon needs to be wary of leaving deformed cartilage in place,
which can cause renewed obstruction. Deformed cartilage can be crushed or scored to
reduce the likelihood of memory in the cartilage, which can cause poor results. These
methods often fail to prevent the cartilage from returning to its curved, undesirable
configuration. After the cartilaginous structure is fixed, the septal flaps are approximated
with a horizontal mattress (plicating) absorbable suture. Nasal splints or nasal packing
sometimes are used. Submucous turbinate resection and other related procedures can be
performed to increase the effectiveness of septoplasty in restoring nasal patency.
Combined with septoplasty, rhinoplasty serves as an external complement. In the
management of obstruction, rhinoplasty is used primarily as a functional rather than a
cosmetic procedure. It is performed through the intranasal or external route. Exposure is
gained and conservative resection of redundant cartilage or bone is performed along the
nasal dorsum. Rhinoplasty techniques are discussed extensively later in Chapter 174,
Chapter 175, Chapter 176, Chapter 177 and Chapter 178.
Turbinate Hypertrophy
Edematous turbinates, whether the primary or secondary cause of nasal obstruction, often
can be managed by medical or surgical means. Medical treatment targets hypertrophic
turbinates that are primarily mucosal in origin. Surgical treatment usually is reserved for
structural (bony) abnormalities. The formation of bony abnormalities may be the long-
term result of prolonged hypertrophy of mucosal tissue or the result of traumatic injury to
the septum with associated enlargement of the nasal turbinates. Mucosal hypertrophy is
caused by disease or perturbation that increases mucosal edema. Physiologic models of
nasal airflow show 50% of inspired air flows along the inferior extent of the inferior
turbinate or between the middle and inferior turbinates, that is, the middle airway (2).
Inferior turbinate hypertrophy that constricts the middle and inferior airways has a
marked effect on nasal airflow. Conditions that produce hypertrophy include infectious,
allergic, and vasomotor rhinitis.
Surgical treatment ranges from lateral repositioning without resection (outfracture) to
bone resection, removal of redundant mucosa, or both. Inferior turbinectomy frequently is
combined with septoplasty to manage contralateral exacerbation of septal deviation.
Although inferior turbinectomy is indicated when mucosal hypertrophy is not responsive
to medication, resection should be conservative. Morbidity associated with radical
inferior turbinate resection includes hemorrhage, ozena, and atrophic rhinitis (4).
Complete removal of the inferior turbinate should not be performed. The surgeon must
weigh the extent of the proposed resection against the nature of nasal obstruction; longer-
lasting obstruction may necessitate more extensive resection.
Conservative submucous turbinate resection, also known as inferior turbinoplasty, has
been shown to yield at least 3 to 5 years of relief from mucosal and bony hypertrophy of
the turbinate with none of the previously mentioned sequelae of turbinate resection, such
as excessive bleeding, crusting, foul nasal discharge, and constant postnasal drainage (5).
However, submucosal turbinate resection alone cannot be used to manage nasal
obstruction because of chronic hypertrophy of the nasal mucosa. The physician must
address the underlying cause of mucosal hypertrophy to achieve a good surgical result.
Submucous resection is performed when the inferior turbinate projects medially and
obstructs the nasal cavity or when hypertrophic turbinate mucosa remains unresponsive
to vigorous medical management (Table 26.6). When performed as an isolated procedure,
inferior turbinate resection proceeds after vigorous anesthesia and vasoconstriction of the
turbinate and lateral nasal wall. After a posterior to anterior incision is made along the
inferior aspect of the inferior turbinate, the mucoperiosteum is elevated off the medial
and lateral aspects of the turbinate bone. The turbinate bone is fractured and reduced with
a Jansen-Middleson rongeur or Takahashi forceps. The superior and inferior
mucoperiosteal flaps are carefully preserved. Redundant mucosa is trimmed from the
inferior mucoperiosteal flap, and the superior mucoperiosteal flap is placed laterally over
the resected inferior turbinate. The mucoperiosteal flap is gently packed in place for 4 to
6 days with antibiotic-impregnated petrolatum gauze to ensure proper adhesion and
healing of the mucoperiosteum to the resected turbinate bone. An alternative is to place
horizontal (plicating) mattress sutures through a minimally resected turbinate to obviate
uncomfortable nasal packing.

TABLE 26.6. EMERGENCIES NASAL
OBSTRUCTION



Chronic hyperplastic mucosal disorders, such as vasomotor rhinitis, frequently
necessitate surgical treatment such as limited ablation of pathologic mucosa on the
inferior turbinates. Therapy such as intraturbinal injection, cryotherapy, electrocautery,
and laser ablation have been used with some degree of success to manage vasomotor
rhinitis. Intraturbinal injection has long been associated with complications such as
blindness from retinal embolism or vasospasm. Care must be taken to prevent injection of
major vessels in the nasal turbinates. This technique should be used rarely, if at all.
Electrocautery is effective in ablating diseased nasal mucosa; however, with needle
cautery, it is difficult to control the extent of submucosal tissue damage. Laser ablation
can be used with more control of submucosal damage and has been used with success to
manage vasomotor rhinitis (6).
In functional endoscopic sinus surgery or intranasal ethmoidectomy, partial or subtotal
middle turbinectomy has been performed with few deleterious effects to nasal airflow or
nasal resistance (7,8); however, many surgeons favor preservation of the middle
turbinate, particularly anteriorly, as a landmark for revision sinus surgery, if needed.
Subjective (symptom scoring) and objective (rhinomanometric, acoustic rhinometric)
postoperative evaluation of these surgical therapies for nasal obstruction suggests that
septoplasty with submucosal inferior turbinate resection and lateral outfracture is the
most effective modality (9). However, for patients with slight anterior septal deviation
(more than 0.4 cm
2
in acoustically determined cross-sectional area ipsilateral to the
deviation), submucosal turbinate resection has contributed little toward nasal patency
(10). In this case, submucosal turbinate resection is contraindicated.
Ablative turbinate surgery is used to reduce obstructive hypertrophic nasal mucosa
through an intramucosal or extramucosal destructive procedure such as cryotherapy,
electrocautery, or laser ablation. Used alone these procedures reduce nasal obstruction
due to mucosal hypertrophy, not anatomic deviation. After turbinate ablation, if the
source of nasal irritation and mucosal hypertrophy is not eliminated, such as removal of
sources of dust or mold allergy or alteration of diet to exclude suspected allergens, the
physician should anticipate recurrence of mucosal hypertrophy.
Septal Perforation
Septal perforation can be asymptomatic; however, this condition often is associated with
crusting and bleeding around the defect and, if the perforation is small, whistling during
inspiration or expiration. Turbinates adjacent to the septal perforation can become
hypertrophic from an increase in the intensity of nasal turbulence. If the perforation is
tolerable and causes no serious detriment to nasal function, management is oriented
toward alleviating the symptoms of perforation. Antibiotic ointment can be used to
control crusting and bleeding around the perforation. A polymeric silicone button can be
used to stop the whistling during inspiration or expiration. These buttons can be shaped to
the individual perforation and usually are well tolerated.
Repair of septal perforation limited to defects less than 2 cm in diameter can be
accomplished with surgical flaps. Under surgical microscopic visualization and with an
intranasal approach, septal repair frequently necessitates sliding or rotating
mucoperichondrial or periosteal flaps across the defect. An advantage of using two
overlapping raw flaps is that the flaps have a propensity to heal and stay moist (11).
Additional procedures involve bilateral mucosal advancement flaps freed from adjacent
septal cartilage or bone, the nasal floor, and the lateral nasal wall. An incision along the
inferior turbinate allows rotation and occlusion of the perforation with the two flaps. A
continuous horizontal mattress suture or whipstitch with 5-0 or 4-0 chromic catgut
plicates the flaps. A small incision or tear at the inferoposterior edge of the flap can
prevent formation of a submucosal hematoma.
Meticulous surgical technique is essential to a successful outcome. Flap healing can be
enhanced with skull-based periosteal or perichondrial grafts sandwiched between the
mucosal flaps. Surgical repair of large perforations is difficult, often necessitating
external rhinoplasty or lateral alotomy (incision along the alar cartilage and maxillary
crease) for sufficient access to the nasal area. Septal perforation due to nose picking often
is easy to close because of the preservation of healthy adjacent cartilage, whereas
perforation due to overzealous resection of septal cartilage (with subsequent breakdown
of mucosa) has a dismal repair prognosis. Similarly difficult procedures are those to
manage septal perforation due to recreational use of cocaine. In these cases, extensive
sections of septal cartilage can be lost owing to extensive vasoconstriction and irritation
of nasal mucosa by cocaine and substances with which it is cut, such as talc or strychnine.
Valvular Collapse
The nasal valve is the narrowest portion of the noses of white persons. When insufficient
cartilaginous support is present, negative (inspiratory) pressure within the nasal cavity
can collapse soft tissue in this region. The internal nasal valve comprises the caudal end
of the upper lateral cartilage and the nasal septum, whereas the internal nasal valve or
external nasal valve contains additional anatomic components such as the lower lateral
(alar) cartilage, the anterior head of the inferior turbinate, and the inferior rim of the
piriform aperture (Fig. 26.1, Fig. 26.8) (12). Extranasally the nasal valve constricts
(posterior to the alar cartilage) when there is large negative pressure (inspiration) and
expands when there is large positive pressure (expiration) within the nasal passage.
Incompetence of the nasal valve is confirmed with the Cottle test. In this test, with the
patient breathing lightly, the examiner pulls the patient's cheek laterally to increase the
nasal valve angle and asks the patient whether the maneuver improves ipsilateral nasal
patency. If the maneuver increases patency, the test result is positive; if no improvement
is felt, the test result is negative. Normal nasal valves should have a negative result;
incompetent nasal valves have a positive result. False-positive result can be caused by
alar collapse. False-negative results can be caused by adhesions, stricture of the nasal
valve, or surgical or nonsurgical trauma that displaces the frontal process of the maxilla
(13).
Surgical reconstruction of an incompetent nasal valve should be undertaken with an open
approach that allows clear assessment of operative augmentations. The most successful
operative techniques include systematic alteration of all surrounding internal structures.
Surgical methods have included internal valve spreader cartilage grafts (widening the
apex of the internal valve); suture repair of drooping upper lateral cartilage (a frequent
complication after dorsal hump excision in rhinoplasty); autogenous cartilage grafts, or
allografts as needed, to support the columella; and spanning grafts or simple lateral crus
onlay grafts to support the lateral crura (14). Grafts can be composed of cartilage or
conchal bone from concurrent inferior turbinectomy. The bony or cartilaginous graft
serves as both an inherent structural support and a method for inducing site-specific
scarring, which enhances the stiffness of this region.
Choanal Atresia
Choanal atresia is a genetic disorder in which the posterior choanae unilaterally or
bilaterally fail to develop properly. It occurs in 1 in 5,000 births. Choanal atresia is more
common among girls (2:1), and unilateral atresia is more common than bilateral atresia.
This disorder can be transmitted as an autosomal recessive trait (15). Because newborns
are obligate nose breathers, bilateral atresia is immediately apparent as respiratory
distress. A breathing tube is inserted, and the infant is examined. Characteristics in the
history or found at failure to pass a rubber catheter or nasogastric tube into the pharynx
can provide enough information for a diagnosis. Symptoms of choanal atresia include
failure to thrive due to poor feeding and mucoid discharge from the affected side. The
presence of choanal atresia can be confirmed with visualization of retention material in
the posterior part of the nose on a lateral radiograph with the patient in the supine
position. Anatomic characterization of the deformity with CT can be important for
planning surgical procedures.
In the care of an infant, surgical methods for membranous atresia include puncture of the
choanal membrane and placement of a stent for 6 weeks. If bony atresia is present, the
bony wall can be taken down transnasally with microsurgical techniques followed by
placement of a stent. When suboptimal resection for atresia or choanal stenosis occurs,
transpalatal repair at 3 or 4 years of age is advised.
Unilateral atresia can go unrecognized until adulthood, at which time the patient seeks
medical attention because of possible septal deviation. The septum usually deviates to the
affected side; however, more posterior examination shows atresia. Computed
tomographic scans of this region provide enough information for a diagnosis.
Transpalatal repair is being replaced by endoscopic techniques of repair of atresia in
children and adults (16).
Growths and Neoplasms
Hyperplastic growths that cause nasal airway occlusion include adenoidal hypertrophy,
nasal polyposis, benign and malignant neoplasms, juvenile nasopharyngeal angiofibroma,
and granulomatous disease. Of these, adenoidal hypertrophy and nasal polyposis are the
first and second most common lesions. Papilloma and salivary neoplasms are the most
common benign neoplasms. Squamous cell carcinoma is the most common malignant
neoplasm. Malignant tumors of the nasal cavity are discussed in Chapter 105 and Chapter
116.
Adenoidal Hypertrophy
Adenoidal hypertrophy is most common among children but occasionally occurs among
adults. The classic clinical presentation of a child with chronic adenoidal hypertrophy has
been called adenoidal facies. This mouth-open, head-up posture is caused by chronic
nasal obstruction that decreases when the head is tilted. Maintenance of this posture is
associated with improper orofacial development, such as a dry, thin upper lip,
retrognathic mandible, narrowed maxilla, broad nasal arch, and an upturned nose with
visible nostrils. Cervical spinal complications attributed to the head-tilted position
include lordosis and kyphosis. The pathophysiologic cause of these conditions is lack of
use or atypical use of the involved anatomic structures with associated effects in the
supporting muscles. Because of the anatomic placement of the adenoid glands, adenoidal
hypertrophy has been associated with eustachian tube dysfunction and associated
conditions of serous and recurrent purulent otitis media. Severe cases can manifest in
conditions such as sleep apnea, pulmonary hypertension, and enlargement of the right
ventricle. In a small-group study (17), administration of beclomethasone dipropionate
was successful in the management of adenoidal hypertrophy among children 5 to 11
years of age. Adenoidectomy is the proper surgical treatment (see Chapter 81).
Nasal Polyposis
Nasal polyps are pale yellow to clear single- or multiple-peduncled benign nasal masses
arising from mucoperiosteal or mucoperichondrial tissue and filled with edematous
stroma and inflammatory cells (Fig. 26.9). These masses can grow through an
accumulation of intracellular fluid, contributed by a random vascular bed, deposition of
polysaccharides, elevated sodium absorption, and increased chloride ion permeability
relative to normal submucosa (18). Successive episodes of localized inflammatory edema
can facilitate transformation from normal to polypoid abnormal submucosa. Recurrent
nasal polyposis has been associated with aspirin triad disease or the Samter triad
(concurrent aspirin sensitivity, asthma, and nasal polyposis), cystic fibrosis (strongly
suggested among children with polyps), and fungal sinus infection. Immunoglobulin E
mediated allergic mechanisms have not been definitively found to be an important factor
in nasal polyposis. Among children, nasal polyposis usually is associated with cystic
fibrosis or asthma. These patients should undergo screening for those associated diseases
(19).

FIGURE 26.9. Photograph shows nasal polyps in an
adult. The obstructive potential of nasal polyps is
apparent. These polyps extend out of the nasal vestibule.



Nasal polyposis is characterized by chronic eosinophilic inflammation. These eosinophils
and other inflammatory cells, such as mast cells and neutrophils, produce cytokines and
other inflammatory mediators (18). The mediators can increase polyp water retention by
increasing sodium ion uptake. Among patients with aspirin triad disease, aspirin is
believed to block cyclooxygenase metabolism of arachidonic acid while stimulating 5-
lipooxygenase, which leads to overproduction of leukotrienes. Leukotrienes increase
vascular permeability, increase mucous secretion, and cause bronchoconstriction.
Patients with nasal or sinonasal polyposis typically have progressive nasal stuffiness,
rhinorrhea, and facial pain or headaches not necessarily associated with the extent of
disease or with a particular nasal region located just internal to a focus of pain. Anosmia
occurs less frequently and is directly related to the extent of polyposis. The most
important adverse effect of nasal polyposis is swelling of the infundibulum, followed by
obstructive sinonasal disease and recurrent or chronic sinusitis. An inverted papilloma or
other neoplasm, such as olfactory esthesioneuroblastoma, although they are exceedingly
rare, can resemble benign polyp tissue. On paranasal sinus CT scans, isolated polypoid
masses predominate when disease involves the nasal cavity. Air-fluid levels of the same
approximate density can preclude delineation of these edematous masses in the sinuses.
Computed tomography can be used to characterize the extent of disease so that
appropriate therapy can be devised.
Medical management of nasal polyps with corticosteroids has met with some success.
Intranasal glucocorticoids interfere with several steps in the inflammatory process. They
decrease capillary permeability, decrease excretion in response to cholinergic stimulation
in the nasal mucosa, and suppress cytokine synthesis in eosinophils, basophils, and
lymphocytes (18). Glucocorticoids inhibit the influx of eosinophils and basophils into the
nasal epithelium and decrease production of inflammatory mediators from arachidonic
acid production (20). Nasal glucocorticoids have proved efficacious in reducing polyp
size and reducing the recurrence of polyps after sinus surgery (21). Systemic
glucocorticoids, administered in a short high burst with a rapid taper, have been used to
manage this recurrent condition. Surgical intervention is indicated when polyposis is
unresponsive to repeated courses of glucocorticoids and when antibiotic-resistant
sinusitis is present. Oral antileukotriene medications have promise for the management of
nasal polyposis due to aspirin triad disease (22).
Surgical excision of nasal polyps occurs solely or in concert with functional endoscopic
sinus surgery and turbinectomy. Longer periods of remission are likely with endoscopic
sinus surgery than with polypectomy alone, except in the care of patients with cystic
fibrosis, among whom recurrence is equally likely regardless of approach (19). The
surgical approach usually is intranasal. The Caldwell-Luc (alveolar fossa) approach
rarely is indicated. Preoperative thin-section CT is recommended for determining the
extent and characteristics of the disease and the associated surgical procedure and for
identifying the variations in this complex anatomic field. The otolaryngologist must be
prudent in preoperative counseling of patients with polyposis, because this condition is
characterized by the need for several operations and by recurrence. If polypectomy can
delay recurrence for 5 years or more, the surgical procedure is deemed successful.
Mucosal Disease
Disorders of the nasal mucosa are perhaps the most common causes of nasal obstruction.
Although rarely fatal, mucosal disease causes serious economic morbidity. Lost wages
and decreased productivity cost several hundred million dollars annually. The diagnosis
and management of rhinitis as a cause of nasal obstruction are discussed in Chapter 24
and Chapter 25.
Miscellaneous Causes of Nasal Obstruction
Septal Hematoma
Frequently the result of traumatic injury to the nose, septal hematoma often manifests as
bilateral obstruction (Fig. 26.10). This condition necessitates immediate treatment.
Avascular septal cartilage begins to degenerate when the septal perichondrium, its
nutrient supply, is nonadherent. Septal degeneration can cause partial or total loss of
support of the dorsum of the nose. The result is a characteristic saddle-nose deformity.
Epistaxis after traumatic injury usually precludes development of septal hematoma,
because blood from epistaxis has a direct exit from the perichondrial space. Management
of septal hematoma involves unilateral or bilateral anterior vertical (Killian) incisions
through the perichondrium, depending on whether the hematoma is unilateral or bilateral.
The Killian incision is made 1 cm parallel to the caudal septal margin. Bilateral incisions
should be stepped (staggered posterior and anterior) to prevent through-and-through
septal weakness or perforation. After blood within the hematoma is evacuated and
bleeding in the region is halted, the nose is packed bilaterally to ensure plication of the
perichondrium with the septal cartilage. Broad-spectrum antibiotics are administered for
prophylaxis against infection and the development of a septal abscess.

FIGURE 26.10. Bilateral septal hematoma (arrows).
This condition necessitates immediate bilateral drainage
to avoid necrosis of the septal cartilage and development
of saddle-nose deformity.



Septal Abscess
A nasal septal abscess forms when a septal hematoma is left uncontrolled. This condition
is managed to prevent further separation of the septal cartilage from its corresponding
perichondrium and to avoid drainage of infected blood into the intracranial space through
nonvalved veins in this region. Transmission of infection from this danger trianglethe
area bounded by the nasion and the lateral edges of the lipscan cause intracranial
thrombosis in the cavernous sinus. Management involves incision and drainage of the
septal abscess with the patient under general anesthesia and being given appropriate
systemic antibiotics. Staphylococcus aureus is the most common pathogen, but
Streptococcus pneumoniae, Haemophilus influenzae, and anaerobic bacteria also can play
a role. Initial therapy must be broad-spectrum antibiotics, which can be narrowed
according to culture results (23).
Foreign Bodies
The presence of an intranasal foreign body is suggested by the history or by the
presenting symptom of unilateral purulent rhinorrhea, especially among infants or
patients with mental disability. Less common causes of obstruction by foreign bodies can
be iatrogenic or of unknown origin, such as rhinolith. Treatment usually is administered
with local anesthesia; rarely is general anesthesia or an open surgical approach used.
Relapsing Polychondritis
Relapsing polychondritis with the formation of saddle-nose deformity can cause nasal
obstruction due to associated loss of cartilaginous support in the nasal septum. This
condition is suggested by a history of pain within and across the dorsum of the nose with
associated erythema. Additional support for this diagnosis is obtained with evidence of
cartilaginous irritation elsewhere, such as the ear, rib cartilage, or articular surfaces.
Treatment includes a course of oral corticosteroids approximated to the extent of the
condition or pain.
Granulomatous Disease
Rhinitis and nasal obstruction can be caused by granulomatous disease of the nose and
paranasal sinuses. Mass lesions can cause nasal obstruction through direct occlusion of
the nasal cavity or through an intranasal inflammatory reaction that produces viscous
secretions, crusting, and nasal passage occlusion. In the United States, the most common
granulomas include polymorphic reticulosis, nonhealing lethal midline granuloma,
Wegener granulomatosis, rhinoscleroma, sarcoidosis, and tuberculosis. Nasal obstruction
can be caused by additional granulomatous infections such as blastomycosis,
coccidioidomycosis, histoplasmosis, leprosy, sporotrichosis, and syphilis; however, these
infectious processes are rare in the United States. Efficacious management of these
conditions is direct medical control of the pathogenic organism.
Rhinoscleroma
Rhinoscleroma is endemic to Central and South America, eastern Europe, and India;
however, with heightened migration to the United States, physicians see this condition
more frequently. Rhinoscleroma is a chronic condition caused by the Klebsiella
rhinoscleromatis organisms. The infection involves the larynx, trachea, bronchi, nose,
and paranasal sinuses. This progressive disease begins with a catarrhal stage
characterized by weeks or months of foul-smelling purulent nasal discharge. It moves
into the atrophic phase, in which the patient has nasal obstruction due to formation of
large nasal plaques and crust. In the granulomatous stage, multiple granulomatous
nodules form and coalesce in the fibrotic stage, which produces severe obstruction when
this disease involves the nasal cavity.
Diagnosis of rhinoscleroma is made by means of bacterial culture with histologic
identification of granuloma, fibrosis, eosinophilic Russell bodies, and large vacuolated
histiocytes (Mikulicz cells). These findings confirm the diagnosis during the
granulomatous stage. Before entering the fibrotic phase, rhinoscleroma can be managed
with antibiotics such as streptomycin and tetracycline. If the disease has progressed into
the fibrotic stage, surgical treatment is indicated. The procedure usually includes
resection of fibrotic tissue and intranasal stent placement to restore and ensure nasal
patency.
Sarcoidosis
Sarcoidosis is an idiopathic granulomatous disease involving the nose, other regions of
the respiratory tract, and additional organ systems, such as skin or kidneys. This disease
frequently appears as small, circumscribed, elevated lesions (papules) on the external
nose or as thickening and engorgement of the anterior nasal mucosa. Microscopic
examination shows that a granuloma looks like salt crystals, or small, locally raised, clear
swellings on the nasal mucosa. At histologic examination diagnostic finding are
noncaseating granuloma, histiocytes, inflammatory multinucleated giant cells, and
caseating or noncaseating focal necrosis. Chest radiographs may show hilar adenopathy,
also known as the pawnbroker's sign (three balls). Diagnosis of this condition can be
difficult before histologic changes are found in a biopsy specimen of tissue in a site of
local involvement. Management of sarcoidosis is symptomatic. It usually is a course of
systemic corticosteroids or intranasal submucosal injection to relieve the nasal
obstruction that usually accompanies this condition.
Tuberculosis
Although tuberculosis had become scarce in the United States, the acquired
immunodeficiency syndrome epidemic and development of antibiotic-resistant strains of
this mycobacterial species have increased the incidence in recent years. Tuberculosis can
involve the nose and paranasal sinuses primarily or secondarily as part of a diffuse
respiratory or systemic infection. Intranasal infection usually involves the anterior
portions of the turbinate and septum. Obstructive intranasal involvement usually is
accompanied by clear or purulent rhinorrhea and pain. Local intranasal tuberculosis
manifests as erythematous nodules in the submucosa. Histopathologic examination shows
caseating necrosis in the center of granulomas containing epithelioid cells (mononuclear
phagocytes) and multinucleated giant cells (Langerhans cells). Histologic staining of
infected tissue is accomplished with acid-fast dyes. Pathogenic organisms are slow
growing in vitro and are difficult to culture.
Medical therapy for tuberculosis can be accomplished with pharmaceuticals such as
isoniazid, streptomycin, p-aminosalicylic acid, rifampin, and ethambutol. These
pharmaceuticals can be used alone or in combination. Consultation with infectious
disease specialists is indicated for effective treatment of patients with tuberculosis and
other, less prevalent infections.
CONCLUSION
Nasal obstruction is one of the most frequent disorders in otolaryngology practice.
Although nasal obstruction often is associated with common rhinitis, the specific cause of
this condition must be identified to achieve successful treatment. Some causes of nasal
obstruction can be successfully managed with medical therapy, such as topical nasal
corticosteroids or surgical intervention, such as submucosal turbinate resection. Other
causes, such as rhinitis of pregnancy, can be self-limiting, necessitating no treatment
except expectant observation. Other causes of nasal obstruction, such as viral rhinitis, can
be managed only symptomatically. Mortality due solely to nasal obstruction is extremely
uncommon; however, there can be profound morbidity associated with this condition.
Some conditions, such as recurrent nasal polyposis, are difficult to manage with a single
medical or surgical treatment and are characterized by several recurrences. Other
conditions, such as nasal obstruction due to nasal septal deviation, can be managed
effectively with septoplasty. Emergency treatment is needed in cases of nasal obstruction
due to septal hematoma or septal abscess to prevent degeneration of the septal cartilage
and development of saddle-nose deformity or the transmittance of infection into the
cavernous sinus.

HIGHLIGHTS
Nasal obstruction is one of the most common symptoms in
otolaryngologic practice. In the United States, medical
expenditures to relieve nasal obstruction or congestion
approximate $5 billion annually.
In addition to the history, physical examination of the nose by
means of direct and endoscopic visualization discloses most
cases of nasal obstruction and allows confirmation through tests
for common causes of nasal obstruction.
Computed tomography of the sinuses without contrast material
is the most helpful auxiliary examination for evaluating nasal
obstruction.
There is no universally accepted functional test of nasal
obstruction as there is audiography for auditory function.
Rhinomanometry and acoustic rhinometry are promising.
Septal hematoma and infected septal hematoma are the two
causes of nasal obstruction that necessitate emergency
management.
Neoplasms are uncommon causes of nasal obstruction, but they
must be ruled out.
Unilateral nasal obstruction most likely is caused by an
obstructive anatomic abnormality, such as a neoplasm or
deviated septum, whereas bilateral nasal obstruction is most
commonly caused by a systemic cause, such as allergy.
Rhinitis medicamentosa is difficult to control without full
patient compliance.
Aspirin sensitivity, asthma, and sinonasal polyposis, known
commonly as the Samter triad, is difficult to manage. It is
characterized by recurrent sinonasal polyposis despite repeated
operations on the sinuses and polypectomy.
CHAPTER REFERENCES
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2. Hahn I, Scherer PW, Mozell MM. Velocity profiles measured for airflow through a large-scale
model of the human nasal cavity. J Appl Physiol 1993;75:22732287.
3. Thaler ER, Bruney FC, Kennedy DW, et al. Use of an electronic nose to distinguish cerebrospinal
fluid from serum. Arch Otolaryngol Head Neck Surg 2000;126:7174.
4. Moore GF, Freeman TJ, Ogren FP, et al. Extended follow-up of total inferior turbinate resection
for relief of chronic nasal obstruction. Laryngoscope 1985;95:10951099.
5. Mabry RL. Inferior turbinoplasty: patient selection, technique, and long-term consequences.
Otolaryngol Head Neck Surg 1988;98:6066.
6. Metson R. Holium:YAG laser endoscopic sinus surgery: a randomized, controlled study.
Laryngoscope 1996;77[Suppl]:118.
7. Cook PR, Begegni A, Bryant WC, et al. Effect of partial middle turbinectomy on nasal airflow and
resistance. Otolaryngol Head Neck Surg 1995;113:413419.
8. Lawson W. The intranasal ethmoidectomy: evolution and an assessment of the procedure.
Laryngoscope 1994;104:149.
9. Samad I, Stevens HE, Maloney A. The efficacy of nasal septal surgery. J Otolaryngol
1992;21:8891.
10. Grymer LF, Illum P, Hilberg O. Septoplasty and compensatory inferior turbinate hypertrophy: a
randomized study evaluated by acoustic rhinometry. J Laryngol Otol 1993;107:413417.
11. Mladina R, Heinzel B. Cross-stealing technique for septal perforation closure. Rhinology
1995;33:174176.
12. Woodhead CJ. Piriform aperture surgery for alar collapse. Clin Otolaryngol 1995;20:7479.
13. Kasperbauer JL, Kern EB. Nasal valve physiology: implications in nasal surgery. Otolaryngol
Clin North Am 1987;20:699719.
14. Teichgraeber JF, Wainright DJ. The treatment of nasal valve obstruction. Plast Reconstr Surg
1994;93:11741182.
15. Gershoni-Baruch R. Choanal atresia: evidence for autosomal recessive inheritence. Am J Med
Genet 1992;44:754756.
16. Josephson GD, Vickery CL, Giles WC, et al. Transnasal endoscopic repair of congenital choanal
atresia. Arch Otolaryngol Head Neck Surg 1998;124:537540.
17. Demain JG, Goetz DW. Pediatric adenoidal hypertrophy and nasal airway obstruction: reduction
with aqueous nasal beclomethasone. Pediatrics 1995;95:355364.
18. Bernstein JM, Yankaskas JR. Increased ion transport in cultured nasal polyp epithelial cells. Arch
Otolaryngol Head Neck Surg 1994;120:993996.
19. Triglia JM, Nicollas R. Nasal and sinus polyposis in children. Laryngoscope 1997;107:963966.
20. Bachert C, Geveart P. Effect of intranasal corticosteroids on release of cytokines and
inflammatory mediators. Allergy 1999;54[Suppl 57]:116123.
21. Kanai N, Denburg J, Jordana M, et al. Nasal polyp inflammation: effect of topical nasal steroid.
Am J Respir Crit Care Med 1994;150:10941100.
22. Ulualp SO, Sterman BM, Toohill RJ. Antileukotriene therapy for the relief of sinus symptoms in
aspirin triad disease. Ear Nose Throat J 1999;78:604616.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

27 MIDLINE NASAL MASSES
Head & Neck SurgeryOtolaryngology
27




MIDLINE NASAL MASSES
SHAREN J. KNUDSEN
BYRON J. BAILEY

S.J. Knudsen: Beaver Medical Group, Inc., Highland, California.
B.J. Bailey: Department of Otolaryngology, University of Texas Medical Branch at Galveston, Galveston,
Texas.


Nasal Embryology
Nasal Anatomy
Congenital Midline Masses
Neurogenic Tumors
Neurofibroma
Dermoid Cyst
Hemangioma
Nasopharyngeal Masses
Nasopharyngeal Cysts
Nasopharyngeal Teratoma
Acquired Midline Nasal Masses
Infection
Furuncle
Septal Abscess
Rhinoscleroma
Rhinosporidiosis
Other Infectious Granulomatous Diseases
Benign Lesions
Malignant Lesions
Idiopathic and Inflammatory Disease
Chapter References
Evaluation of a midline nasal mass requires a systematic approach. Knowledge of
embryology of the nose and midface aids in understanding the origin of congenital
midfacial deformities that manifest as nasal masses. A congenital mass mandates a
differential diagnosis different from that of an acquired nasal mass. An acquired mass
may be infectious, inflammatory, or neoplastic in origin. This chapter describes
pathologic conditions of the nose and midface and delineates the essential elements of
incidence, history, and physical examination necessary for generating a diagnosis and
treatment strategy.
NASAL EMBRYOLOGY
During the third week of fetal life, a massive frontonasal process develops. The first
branchial arch, which divides into the maxillary and mandibular processes, is inferior to
the frontonasal process. Ectoderm on the lateral surface of the frontonasal process
invaginates to form the nasal pit. The olfactory placode develops around the pit as a
horseshoe-shaped tissue mass with a lateral and medial process (Fig. 27.1A).

FIGURE 27.1. A: Frontal view of a 5-week embryo. B:
Frontal view of a 7-week embryo. During the fifth week,
the nasal placodes sink to become the nasal pits.
Mesodermal growth centers proliferate and fuse around
the pits. During the sixth through eighth weeks, the pits
deepen to the ectoderm at the roof of the mouth to form
the bucconasal membrane at the choanae. The septum
forms from the mesoderm between the pits. (Redrawn
with permission from Langman J. Medical embryology: human developmentnormal
and abnormal. Baltimore: Williams & Wilkins, 1963.)



Synchronous events during the fifth through eighth weeks of fetal life produce the
definitive structures of the midface. The frontonasal process descends to become the
bridge and apex of the nose. The olfactory placodes migrate to the midline and fuse to
become the nose (Fig. 27.1B). The maxillary processes fuse to form the upper jaw.
Midfacial development is a complex event with convergence of the developing sensory
organs and respiratory and digestive systems. Congenital defects can occur in regions
where all three germ layers interact during developmental activity. In contrast, the
mandible develops earlier from a single arch, and fewer congenital anomalies occur in the
mandible than in the midface-maxillary region. The medial nasal processes contribute the
columella, philtrum, and upper lip. The lateral process fuses with the medial nasal
process to form the maxillary arch. The nasofrontal process descends and compresses
laterally to form the nasal septum. The medial nasal process contributes to the premaxilla.
In the seventh week of fetal life, chondrification begins in the dense mesenchyma at the
caudal end of the notochord. The ethmoid, sphenoid, occipital, temporal, and skull base
elements form the chondrocranium. The osteocranium is largely made up of membranous
bone, including the vomer, nasal, lacrimal, palate, maxilla, premaxilla, frontal, and
parietal bones.
NASAL ANATOMY
The nasal skeleton consists of two paired nasal bones, the nasal process of the maxilla,
and the upper and lower lateral cartilages. The septum is composed of the vomer,
perpendicular plate of the ethmoid bone, and the quadrangular cartilage. The three paired
turbinates, the ethmoid air cells, and the sphenoid bone form the endonasal skeleton.
The nasopharynx is the space from the choanae to the free edge of the soft palate. This
rigid space contains the eustachian tube orifice, the Rosenmller fossa, and the adenoid
lymph tissue. The sphenoid fossa, which is posterosuperior to the insertion of the middle
turbinate, houses the ganglion that bears the same name. Two important embryologic
defects can occur in the nasopharynx. Rathke pouch is a remnant of the invagination of
ectoderm that forms the anterior pituitary gland. Cysts of Rathke pouch are located high
in the nasopharynx near the sphenovomer junction. The cysts can become infected.
Tumors in this region are called craniopharyngioma and are composed of well-
differentiated epithelial elements. Although the bulk of these tumors extend
intracranially, they can occur in the nasopharynx. Symptoms include nasal obstruction
with neurologic signs of visual field defects, extraocular motility disorders, and
hypopituitarism. Treatment consists of surgery or radiation therapy.
The nasopharyngeal bursa of Tornwaldt is inferior to the Rathke pouch and is a remnant
of the caudal notochord. Jelly-like material that persists in this bursa can become
infected. A swollen, infected bursa that manifests as a nasopharyngeal mass can rupture if
manipulated. Figure 27.2 is a computed tomographic (CT) scan that shows a Tornwaldt
bursa. Treatment is excision or marsupialization.

FIGURE 27.2. Computed tomographic scan shows a
Thornwaldt bursa. Arrow points toward the air-containing
bursa in the nasopharynx.



CONGENITAL MIDLINE MASSES
Neurogenic Tumors
Neurogenic tumors are best classified according to embryonic cells of origin. These
benign tumors encroach on the nasal framework and distort the anatomic configuration of
the nose. Early removal is advised, and successful treatment necessitates knowledge of
embryonic anatomic relations (Fig. 27.3). The anterior wall of the developing nose is
cartilaginous. In front of this cartilage, the nasal and frontal bones develop within a
mesenchymal layer. The frontal bones initially are not fused, and the space between them
is called the fonticulus frontalis. The prenasal space exists between the nasal bones
anteriorly and the cartilage posteriorly. Dura can project into this area through the
foramen cecum at the base of the frontal bone. In normal development, this dural canal is
obliterated. Any defect in this process leaves a pathway for neural tissue to extend to the
prenasal space close to the nasal skin. The incidence of these disorders is estimated at 1
in 20,000 to 40,000 live births. Figure 27.4, Figure 27.5, and Figure 27.6 show the
midline structures involved with congenital neurogenic tumors and sinus tracks.

FIGURE 27.3. Sagittal section of the developing anterior
base of the skull shows the prenasal space during normal
fetal growth. The developing nasal bones are separated
from the frontal bones by the fonticulus frontalis. The
prenasal space (P) lies between the anterior nasal bones
and the posterior nasal cartilage. (Redrawn from Van Den
Abbeele T, Elmaleh N, Herman P, et al. Transnasal
endoscopic repair of congenital defects of the skull base
in children. Arch Otolaryngol Head Neck Surg 1999;125:580, with permission.)



FIGURE 27.4. Midsagittal section of the developing
anterior base of the skull shows the course of an
extranasal glioma. (Redrawn from Van Den Abbeele T,
Elmaleh N, Herman P, et al. Transnasal endoscopic repair
of congenital defects of the skull base in children. Arch
Otolaryngol Head Neck Surg 1999;125:580, with
permission.)



FIGURE 27.5. Midsagittal section of the developing
base of the skull shows the pathway of a nasal dermal
sinus cyst and track. The pit is visible at the nasion and
the intracranial extension. (Redrawn from Van Den
Abbeele T, Elmaleh N, Herman P, et al. Transnasal
endoscopic repair of congenital defects of the skull base
in children. Arch Otolaryngol Head Neck Surg
1999;125:580, with permission.)



FIGURE 27.6. Cutaneous opening (arrow) to a dermal
sinus track on the dorsum of the nose.



Nasal glioma is a rare lesion at the bridge of the nose near the midline. Sixty percent of
nasal gliomas are extranasal, and 30% are intranasal. The lesion is characterized by a
rounded, skin-covered, nonpulsatile, firm mass. Glioma does not become larger with
crying or straining. Intranasal glioma can appear as a polyp in the mouth, nasopharynx, or
pterygopalatine fossa. The growth rate varies considerably. Boys are more commonly
affected than are girls. Treatment is surgical excision. A CT scan is mandatory in the
preoperative evaluation to rule out intracranial extension, and a biopsy of nasal polyps
may show glial tissue. An intranasal approach suffices for small lesions, and extranasal
combined approaches are used for operations on larger intranasal and all extranasal
lesions. Frontal anterior craniotomy may be needed for operations on lesions with
intracranial extension. Children with nasal glioma have been treated successfully by
means of transnasal endoscopic resection of the glioma with immediate repair of the
skull-base defect with a free mucosal graft, pedicled mucosal flap, or conchal cartilage
with fibrin glue and nasal packing for 3 weeks (1).
Encephalocele is structurally different from glioma because it contains an ependyma-
lined space that contains cerebrospinal fluid (CSF) and communicates directly with the
ventricles. Meningocele contains meninges; meningoencephalocele contains meninges
and brain; and meningoencephalocytocele contains meninges, brain, and part of the
ventricular system. Encephaloceles grow larger with crying and straining. Compression
of the jugular veins, with a resultant increase in CSF pressure, produces enlargement of
the mass, known as a positive Furstenberg test result. Encephalocele looks like glioma,
except that it can be transilluminated. There is always a bony defect. Encephalocele is
five times more common in the lumbosacral area than in the cranium. Of those in the
cranium, 75% are located in the posterior occipital area and 25% in the anterior area.
Sincipital encephalocele involves the frontoethmoid area and is external (Fig. 27.7A).
The bony defect is anterior to the crista galli in the region of the foramen cecum. Basal
lesions manifest themselves internally (Fig. 27.7B). The skull defect is in the floor of the
anterior cranial fossa between the cribriform plate and the clinoid process or through the
superior orbital fissure. Magnetic resonance imaging (MRI) is considered more valuable
than CT scanning because the soft-tissue structures are better delineated without exposure
to ionizing radiation. Treatment involves complete closure of the dural defect to prevent
CSF leaks and excision of irreducible herniated brain tissue. A large defect necessitates a
dural graft. Complications of surgery include meningitis and CSF leak. Table 27.1
summarizes the diagnostic features of congenital neurogenic masses.

FIGURE 27.7. A: Sincipital encephaloceles at the root of
the nose. B: Basal encephaloceles at the base of the skull.
The basal form may have no external manifestations, but
sincipital lesions are frequently obvious. (Redrawn from
Van Den Abbeele T, Elmaleh N, Herman P, et al.
Transnasal endoscopic repair of congenital defects of the
skull base in children. Arch Otolaryngol Head Neck Surg
1999;125:580, with permission.)



TABLE 27.1. CONGENITAL MASSES OF
NEUROECTODERMAL ORIGIN



Neurofibroma
Neurofibroma and schwannoma can occur in the midline. They usually are associated
with generalized neurofibromatosis. Tumor growth along branches of the trigeminal
nerve can occur among patients with neurofibromatosis and produce a painful condition
not unlike tic douloureux. Excision is indicated only when these benign tumors are large
enough to produce facial asymmetry, visual disturbances, or severe pain.
Dermoid Cyst
Ectodermal cysts containing epithelial lining and adnexal tissue have an origin similar to
that of neurogenic tumors. Defective obliteration of the dural projection through the
foramen cecum results in entrapment of epithelial elements as the dural tract resorbs. A
sinus tract results from invagination of the epithelia, which can occur anywhere from
nasal tip to foramen cecum (Fig. 27.8). A cyst forms in a closed tract. Sessions (2) prefers
the term nasal dermal sinus cysts to describe these lesions because most are associated
with a sinus track. Dermoid cysts usually are present at birth and have a sinus opening
anywhere from columella to nasion. A tuft of hair frequently protrudes from the ostia.
Simple dermoid cysts involve only the skin and nasal bones. Complex dermoid cysts can
involve the undersurface of the nasal bones and extend through the cribriform plate to the
dura. The patient usually has a history of meningitis or CSF leak if a dural connection
exists. Surgery is the recommended treatment, but recurrence is common despite a careful
surgical approach (3). Craniotomy is needed for dermoid cysts with known dural
connections, but many complex dermoid cysts can be approached extracranially (4). The
complications of surgery are meningitis and CSF leak.

FIGURE 27.8. Midsagittal section of the developing
skull base with a dermoid cyst and fistula. The arrows
follow the path of the dermoid sinus tract or fistula. This
is the route by which bacteria travel to the meninges to
produce meningitis. (Redrawn from Van Den Abbeele T,
Elmaleh N, Herman P, et al. Transnasal endoscopic repair
of congenital defects of the skull base in children. Arch
Otolaryngol Head Neck Surg 1999;125:580, with
permission.)



Hemangioma
Capillary and cavernous lesions occur in the midline. The partially fibrotic cavernous
type is frequently misdiagnosed. Sclerosing therapy has been a mainstay of treatment.
Laser technology is useful in managing large lesions.
NASOPHARYNGEAL MASSES
Nasopharyngeal Cysts
Three nasopharyngeal cysts have been describedintraadenoidal, extraadenoidal, and
branchial cleft cysts. They manifest as purulent nasal discharge, pain in the throat, and
conductive hearing loss from chronic eustachian tube dysfunction. Intraadenoidal cysts
arise from the median pharyngeal recess and manifest as small openings on the adenoid
bed. Extraadenoidal cysts are located deep in the pharyngobasilar fascia and are derived
from the pharyngeal bursa. A cuff of granulation tissue rostral to the pharyngeal tubercle
is the main physical finding. A mass in the nasopharynx is rare with this cyst. Treatment
is marsupialization of the cyst. Branchial cleft cysts are derived from the first and second
pharyngeal pouches. The cysts usually are paired and located on the lateral walls of the
nasopharynx. Treatment is excision.
Nasopharyngeal Teratoma
Half of all head and neck teratomas occur in the nose. Girls are affected six times more
frequently than boys. Teratoma manifests as sessile or pedunculated masses in the
nasopharynx and is associated with cranial deformity, such as anencephaly, hemicrania,
and palatal fissures. Hair, skin, bone, cartilage, and teeth have been found in teratomas.
ACQUIRED MIDLINE NASAL MASSES
Infection
Infectious nasal disorders manifesting as midline nasal masses are summarized in Table
27.2.

TABLE 27.2. INFECTIOUS NASAL DISORDERS
MANIFESTING AS MIDLINE NASAL MASSES



Furuncle
Furuncle is the most common of the infectious lesions of the nasal vestibule. The
pathogen is Staphylococcus aureus. Treatment consists of drainage and
antistaphylococcal antibiotics. A complication is septal abscess, which causes
suppurative chondritis, cartilage erosion, and saddle-nose deformity.
Septal Abscess
Septal abscess is caused by a furuncle or trauma with resultant septal hematoma.
Parenteral antistaphylococcal antibiotics are important adjuncts to surgical drainage. A
long-term complication is saddle-nose deformity. In a series of patients with hematoma
and abscess of the nasal septum, all 20 patients had a history of nasal trauma, and 19 of
20 had nasal obstruction. Management of hematoma and abscess of the nasal septum is
universally accepted to be urgent surgical drainage and antibiotic therapy.
Rhinoscleroma
The pathogen in rhinoscleroma is Klebsiella rhinoscleromatis. Uncontrolled disease
progresses through catarrhal, granulomatous, and sclerotic stages. Purulent rhinorrhea
lasting weeks to months characterizes the catarrhal stage. The granulomatous stage is
manifested by the formation of soft nodules in the nose, pharynx, larynx, and
tracheobronchial tree. Dense fibrotic narrowing of the nasal passages occurs in the final
cicatricial or sclerotic stage. The histologic appearance of the granulomatous lesions is
characterized by Mikulicz cells, which are foamy histiocytes containing intracellular
Klebsiella organisms (Fig. 27.9). Pseudoepithelial hyperplasia suggesting carcinoma
occurs. Treatment consists of tetracycline, which is effective in 70% of cases when
administered for 4 weeks. Rhinoscleroma can progress to involve the larynx and trachea,
causing progressive airway obstruction. Laryngotracheal lesions may necessitate
operative intervention (tracheotomy, sequential dilation, or laser excision).

FIGURE 27.9. Photomicrograph shows Mikulicz cells in
a rhinoscleroma in a Latin American woman. Large,
foamy histiocytes (giant cells) contain Klebsiella
organisms.



Rhinosporidiosis
Rhinosporidium seeberi organisms cause rhinosporidiosis, which is endemic in India and
Sri Lanka. Public bathing in infected water inoculates the nasal epithelium with
colonizing fungi. A sporangium surrounded by a thick-walled cyst grows in the nasal
vault. Histologic techniques are needed to make the diagnosis because ordinary
mycologic media do not isolate the organism. The lesions are characterized by small
tumor-like masses in the nose, nasopharynx, and eye. The lesions are vascular,
pedunculated, and friable. The symptoms are nasal obstruction, rhinitis, and epistaxis.
Treatment is surgical extirpation with cautery at the base. Depot injections of
amphotericin and steroids have been advocated to manage the 10% of lesions that recur.
Other Infectious Granulomatous Diseases
Leprosy, histoplasmosis, coccidioidomycosis, blastomycosis, and tuberculosis can form
granulomatous lesions in the nose. Diagnosis is based on biopsy and culture results.
Treatment is usually with an antifungal agent such as amphotericin B or fluconazole.
Benign Lesions
Benign Tumors of Ectodermal Origin
Benign neoplastic lesions manifesting as midline nasal masses are summarized in Table
27.3.

TABLE 27.3. BENIGN NEOPLASTIC LESIONS
MANIFESTING AS MIDLINE NASAL MASSES



Papilloma
Verrucous lesions caused by the common cutaneous papillomavirus (warts) are rare in the
nasal vestibules of children. Irritation due to digital trauma produces mild symptoms and
epistaxis. Verrucous papilloma is managed with surgical excision.
Inverting Papilloma
Inverting papilloma has been called by many names, including schneiderian papilloma,
epithelial papilloma of the sinonasal tract, and cylindrical cell papilloma. Men and boys
are affected three times more frequently than women and girls. A proliferation of reserve
cells in the schneiderian mucosa produces the tumor. Inverting papillomas arising on the
nasal septum are characteristically exophytic, and those arising on the lateral nasal wall
and paranasal sinuses are inverting. This distinction has prognostic significance because
malignant growth occurs in as many as 15% of cases of papilloma the lateral nasal wall
and is rare in septal papilloma. Symptoms include unilateral nasal obstruction with or
without sinusitis, rhinorrhea, and epistaxis. The patients often undergo repeated
polypectomy.
Preoperative evaluation includes biopsy, coronal CT studies, and culture for concomitant
nasal pathogens in patients with obstructed sinuses. Figure 27.10 is a CT image of a
patient with inverting papilloma. Treatment is aimed at removal without mutilation of the
tissue and at detection of malignant growth. Despite careful surgical technique, a
recurrence rate of 44% is quoted, and multiple procedures may be needed to control the
disease. Lateral rhinotomy is the approach often used for exposure if there is extensive
disease or a question about the presence of malignant growth. Radiation therapy is
ineffective and thought to induce carcinoma, as in induction of squamous cell carcinoma
in the larynx by human papillomavirus (HPV). Inverted papilloma sometimes involves
both nasal cavities. Bilateral lateral rhinotomy with bilateral medial maxillectomy is
recommended in this situation, because there is a possibility that these lesions are
multicentric (5). It may be possible to achieve a cure rate of 94% with endoscopic medial
maxillectomy (6).

FIGURE 27.10. Computed tomographic scan shows
inverting papilloma involving the entire nasal cavity.
Unilateral involvement and associated unilateral
pansinusitis are evident.



Benign Salivary Gland Tumors
Minor salivary glands are present in abundance in the nasal cavity, but benign salivary
tumors are relatively rare. The most common is mixed tumor (pleomorphic adenoma)
with more than 100 cases described. Treatment is complete surgical excision, and there is
a low recurrence rate. Other salivary tumors are discussed in Chapter 107. The primary
treatment strategy is complete removal without mutilation.
Benign Tumors of Neuroectodermal Origin
Rare tumors of neuroectodermal origin that occur in the nasal cavity include
schwannoma, neurofibroma, traumatic neuroma, and paraganglioma.
Benign Connective Tissue Tumors
Hemangioma
Blood-filled masses in the nasal cavity present a diagnostic challenge to differentiate
among hamartoma, reactive vascular proliferation, pyogenic granuloma, arteriovenous
malformation, and true hemangioma. Hemangioma of pregnancy (granuloma
gravidarum) can involute spontaneously after parturition. It clinically resembles capillary
hemangioma. Hemangiomas often are located on the anterior nasal septum in the area of
the Kisselbach plexus. Patients seek medical attention because of nasal obstruction and
epistaxis. Histologic examination shows polypoid tissue with vascular channels filled
with blood. Treatment is surgical excision with a good prognosis for cure. If the patient is
not treated, the lesions can attain great size and cause bony erosion and disfigurement.
Figure 27.11 shows a woman who sustained blunt trauma to the dorsum of the nose in a
motor vehicle accident. She has a traumatic arteriovenous fistula that was excised without
recurrence.

FIGURE 27.11. Traumatic arteriovenous fistula
involving the dorsum of the nose. This lesion developed
after soft-tissue trauma in a motor vehicle accident.



Angiofibroma
Juvenile angiofibroma arises in the nasopharynx or lateral nasal wall at the posterior
middle turbinate. The tumor occurs exclusively among boys and men and commonly
manifests at puberty. The biologic behavior is that of a nonmetastasizing tumor that is
locally aggressive. The symptoms of nasal obstruction and intermittent epistaxis coupled
with a purplish polypoid nasopharyngeal mass are clues to the vascular nature of this
lesion. Biopsy in a physician's office is considered dangerous because of the high risk of
uncontrollable hemorrhage. Treatment is surgery. Preoperative embolization is important
adjunct to minimize blood loss during extirpation. Radiation therapy and hormonal
manipulation have been used to manage inoperable lesions. Figure 27.12 shows a CT
scan and an arteriogram of a juvenile angiofibroma in a 22-year-old man.

FIGURE 27.12. Images of a patient with a juvenile
angiofibroma. A: Computed tomographic scan shows the
tumor mass. B: Arteriogram shows tumor blush and
feeding vessels.



Juvenile nasopharyngeal angiofibroma can be stimulated to grow rapidly by growth
factors that influence angiogenesis and mesenchymal proliferation. Nagai et al. found
increased levels of insulin-like growth factor II messenger RNA and propose that insulin-
like growth factor II can be one of the important growth regulators for these tumors.
Other authors (7) have emphasized the correlation between large tumor size with invasion
of the skull base and a higher rate of recurrence. Although open surgical approaches are
used most commonly, endoscopic removal after embolization has been shown to be
effective in the treatment of some patients (8).
Benign Tumors of Mesenchymal Origin
Chondroma, osteoma, and bone cyst can occur in the sinonasal tract. Fibrous dysplasia is
a disorder in which normal bone is replaced by fibrous tissue and osteoid. The three
forms of monostotic, polyostotic, and McCune-Albright syndrome (precocious puberty,
hyperpigmentation, hyperthyroidism) are described. The maxilla is most commonly
involved. The histologic appearance of bony trabeculae embedded in a fibrous stroma is
described as Chinese characters (Fig. 27.13). Treatment is conservative; surgery is
reserved for deforming lesions.

FIGURE 27.13. Histologic appearance of fibrous
dysplasia. The bony trabeculae are embedded in fibrous
stroma and look like Chinese calligraphy.



Malignant Lesions
Malignant lesions that manifest as nasal masses are summarized in Table 27.4.

TABLE 27.4. MALIGNANT LESIONS
MANIFESTING AS NASAL MASSES



Malignant Tumors of Epithelial Origin
Squamous Cell Carcinoma
Squamous cell carcinoma is the most common malignant neoplasm of the sinonasal tract.
Carcinoma of the dorsum of the nose and vestibule behaves as other cutaneous epidermal
malignant tumors with a tendency toward differentiation and rare metastasis. Carcinoma
arising in the sinonasal tract has more aggressive behaviora tendency toward less
squamoid differentiation and a higher rate of metastasis. The nasal septum and turbinate
are the most frequent intranasal tumor sites. Nasopharyngeal carcinoma has been
associated with infection by the Epstein-Barr virus, often has a lymphocytic infiltrate, and
is highly radiosensitive. Occupational exposure to certain materials is associated with the
development of squamous cell carcinoma. These include nickel, chromate, flour dust, and
isopropyl alcohol. Patients usually have an ulcerating lesion (Fig. 27.14). Either radiation
therapy or surgical excision is effective management of small, early-stage lesions of the
nasal septum. More advanced lesions must be managed aggressively with surgery and
radiation therapy. Prophylactic neck dissection often is recommended, but the
effectiveness is not clearly established. Early diagnosis is the key to achieving higher
cure rates. Thorough examination is of great importance in the care of patients with
chronic nasal symptoms.

FIGURE 27.14. Squamous cell carcinoma arises from
the nasal septum and erodes the columella.



Basal Cell Carcinoma
Basal cell carcinoma is the most common malignant tumor of the external nose and
vestibule. Lesions are characterized by ulcerated nodules with raised, smooth borders.
Fair-skinned persons with a history of sun exposure are at greatest risk of these locally
aggressive tumors. The tumors rarely metastasize, and most lesions are solitary. Basal
cell nevus syndrome is characterized by multicentric lesions, dentigerous cysts, and
skeletal abnormalities such as bifid ribs, scoliosis, and spina bifida. The genetic disorder
is inherited in an autosomal dominant pattern. Therapy for basal cell carcinoma is
surgical excision, but the surgeon should be wary of tumors that arise near embryonic
cleavage planes because they can extend deep into the dermis. Lesions in these locations
and recurrent lesions are best managed with Mohs micrographic surgery to ensure
complete tumor removal.
Intranasal Verrucous Carcinoma
Verrucous carcinoma of the nasal cavity is rare. Human papillomavirus has been
proposed as an etiologic factor. A report from the Mayo Clinic described successful
surgical management of these tumors by means of wide local excision, but did not prove
any role for HPV as a cause of verrucous carcinoma of the nose (9).
Malignant Salivary Gland Tumors
Adenoid Cystic Carcinoma
Malignant minor salivary gland tumors can arise in the sinonasal tract and occur
anywhere from antrum to nasopharynx. The most common of these is adenoid cystic
carcinoma. Older literature ascribes the name cylindroma to these tumors. Symptoms of
these tumors are similar to those of any nasal mass, except that pain is frequently present
because the tumor spreads along neural tissue. These tumors have an unfavorable
prognosis with a tendency toward hematogenous metastasis to lungs, bone, and brain.
The 10-year survival rate is less than 10%. Treatment is surgery.
Mucoepidermoid Carcinoma
Mucoepidermoid carcinoma rarely occurs in the nose. Both high-grade and low-grade
tumors have been reported. The prognosis is better for low-grade tumors. Overall
mortality is low when the tumor is managed as the more common squamous cell
carcinoma of the sinonasal tract.
Neuroectodermal Lesions
Olfactory Neuroblastoma
Olfactory neuroblastoma (esthesioneurocytoma, esthesioneuroblastoma) arise from the
olfactory tissue, possibly the bipolar neurons. They are uncommon tumors that appear as
a pink or brown friable mass with a gritty texture. Histologic examination shows a
lobular pattern of uniform cells surrounded by a vascular stroma. Aggressive local
growth with occasional metastasis to regional lymph nodes is the usual clinical course.
Treatment is radical surgery with chemotherapy and radiation therapy as adjuncts. These
patients need long-term follow-up care (10).
Malignant Melanoma
Melanoma of the sinonasal tract is second only to squamous cell carcinoma in frequency,
according to the Armed Forces Institute of Pathology otorhinolaryngology records. About
25% of cutaneous lesions occur in the head and neck region. The primary endonasal site
of origin is the nasal septum, where tumors manifest as pigmented masses. Pain,
swelling, nasal obstruction, and epistaxis are the main symptoms. Even with surgical
treatment, a 50% recurrence rate is reported. Prognosis is poor. The median survival rate
for oronasal melanoma is 2 years, and the 5-year survival rate is 25%. Advanced age is an
adverse prognostic factor. Among the reasons for this poor prognosis are lack of
symptoms with early disease, difficulty achieving wide excision margins, and the rich
blood supply in the area. Wide local excision is recommended as the most effective mode
of primary therapy. Lymph node dissection is not usually used to manage stage N0
disease because of the low incidence of nodal metastasis in the absence of local
recurrence or distant metastasis.
Malignant Mesenchymal Tumors
Hemangiopericytoma
Hemangiopericytoma is a rare tumor that arises from the pericytes of Zimmermann,
which are small cells external to the capillary endothelial cells. Pericytes change the
caliber of the vessel. They should always be considered to have malignant potential.
Severe and uncontrollable epistaxis after biopsy has been described. Current therapy
consists of preoperative embolization and en bloc resection of the tumor. Figure 27.15 is
a preoperative CT scan that shows a lesion filling the nasal cavity.

FIGURE 27.15. Preoperative CT scan of a
hemangiopericytoma.



Kaposi Sarcoma
Before the era of acquired immunodeficiency syndrome (AIDS), Kaposi sarcoma
occurred among elderly men, usually on the extremities. Currently most patients with
Kaposi sarcoma are infected with the human immunodeficiency virus and have AIDS.
Dark-brown nodules appear on the skin or mucosa. The histologic appearance is a
capsule surrounding spindle cells with prominent nuclei. Treatment is excision or laser
ablation.
Lymphoreticular Tumor
Lymphoma, Hodgkin disease, and extramedullary plasmacytoma (Fig. 27.16) can occur
in the sinonasal tract.

FIGURE 27.16. Computed tomographic scan shows
extramedullary plasmacytoma (arrow) eroding the nasal
septum. A: Axial view. B: Coronal view.



IDIOPATHIC AND INFLAMMATORY DISEASE
Idiopathic and inflammatory diseases are discussed in Chapter 13 and Chapter 15.

HIGHLIGHTS
Midline nasal mass is a description, not a diagnosis.
Information from the history, physical examination, and
selected imaging studies can generate a precise diagnosis.
Management of a midline mass is begun after a precise
diagnosis is obtained. Most lesions necessitate surgical
intervention.
Knowledge of embryology and anatomy of the nose is essential
for diagnosis and management of congenital midline masses,
particularly glioma, dermoid cyst, and encephalocele.
Acquired midline nasal masses can be caused by infectious,
neoplastic, inflammatory, and idiopathic disorders.
Squamous cell carcinoma is the most common malignant
neoplasm of the sinonasal tract. The biologic behavior of
tumors of the vestibule and dorsum of the nose is that of a
cutaneous malignant tumor. Intranasal lesions have a more
aggressive course and a less favorable prognosis than do
cutaneous lesions.
Malignant melanoma frequently occurs in the head and neck
region. The most common site in the sinonasal tract is the nasal
septum.
Certain benign lesions, such as inverting papilloma and juvenile
angiofibroma, can be locally aggressive and destructive.
Biopsy of vascular intranasal lesions carries a high risk of
hemorrhage. This includes juvenile angiofibroma,
hemangiopericytoma, and hemangioma.
Idiopathic midline destructive diseases include Wegener
granulomatosis and lethal midline granuloma. Wegener
granulomatosis responds to corticosteroids and
cyclophosphamide. Lethal midline granuloma is thought to be
T-cell lymphoma and responds well to radiation therapy.
CHAPTER REFERENCES
1. Van Den Abbeele T, Elmaleh N, Herman P, et al. Transnasal endoscopic repair of congenital
defects of the skull base in children. Arch Otolaryngol Head Neck Surg 1999;125:580584.
2. Sessions RB. Nasal dermal sinus: new concepts and explanations. Laryngoscope 1982;92[Suppl
1]:128.
3. Rohrich RJ, Lowe JB, Schwartz MR. The role of open rhinoplasty in the management of nasal
dermoid cysts. Plast Reconstr Surg 1999;104:14591466.
4. Denoyelle F, Ducroz V, Roger G, et al. Nasal dermoid sinus cysts in children. Laryngoscope
1997;107:795800.
5. Hosal SA, Freeman JL. Bilateral lateral rhinotomy for resection of bilateral inverted papilloma.
Otolaryngol Head Neck Surg 1996;114:103105.
6. Sukenik MA, Casiano R. Endoscopic medial maxillectomy for inverted papillomas of the
paranasal sinuses: value of the intraoperative endoscopic examination. Laryngoscope
2000;110:3942.
7. Herman P, Lot G, Chapot R, et al. Long-term follow-up of juvenile nasopharyngeal
angiofibromas: analysis of recurrences. Laryngoscope 1999;109:140147.
8. Newlands SD, Weymuller EA Jr. Endoscopic treatment of juvenile nasopharyngeal angiofibroma.
Am J Rhinol 1999;13:213219.
9. Orvidas LJ, Lewis JE, Olsen KD, et al. Intranasal verrucous carcinoma: relationship to inverting
papilloma and human papillomavirus. Laryngoscope 1999;109:371375.
10. Levine PA, Gallagher R, Cantrell RW. Esthesioneuroblastoma: reflections of a 21-year
experience. Laryngoscope 1999;109:15391543.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

28 SINUS ANATOMY AND FUNCTION
Head & Neck SurgeryOtolaryngology
28




SINUS ANATOMY AND FUNCTION
RONALD G. AMEDEE
ANDREW J. MILLER

R.G. Amedee: Department of OtolaryngologyHead and Neck Surgery, Tulane University School of
Medicine, New Orleans, Louisiana.
A.J. Miller: St. Peter's University Medical Center, Edison, New Jersey.


Embryology and Development
Anatomy
Ethmoidal Sinus
Maxillary Sinus
Frontal Sinus
Sphenoidal Sinus
Physiology
Sinus Epithelium
Mucous Blanket
The Ostiomeatal Complex
Function of the Paranasal Sinuses
Chapter References
Paranasal sinus anatomy is highly complex and quite variable from person to person.
Differences in structure also can exist between the two sides in the same person. Detailed
knowledge of anatomy of the sinuses is extremely important in performing procedures
such as functional endoscopic sinus surgery, intranasal orbital decompression, and
transsphenoidal hypophysectomy. This chapter provides a comprehensive explanation of
the anatomy and function of the paranasal sinuses. Embryology of the sinuses and
accessory structures is detailed. Anatomy of the sinus is discussed with particular
attention to important landmarks and structural relations. The blood supply and neural
innervation are highlighted in Table 28.1 to provide quick reference and comparison
between the sinuses. Physiology of the paranasal sinuses is reviewed with descriptions of
the sinus epithelium, the mucous blanket, and the ostiomeatal complex. The chapter
concludes with an overview of prevailing theories concerning function of the sinuses.

TABLE 28.1. PARANASAL SINUS BLOOD
SUPPLY AND INNERVATION



There are eight paranasal sinusesfour on the right and four on the left side of the nose.
They are the frontal, ethmoidal (anterior and posterior), maxillary, and sphenoidal
sinuses. Each sinus is lined with a mucous membrane that is continuous with the mucosa
of the nasal cavity through an ostium. Under normal anatomic and physiologic
conditions, the sinuses are filled with air; however, deviations from normal anatomic
structure or changes in mucous membrane function predispose a person to sinus disease.
EMBRYOLOGY AND DEVELOPMENT
It is important to understand the embryology of the paranasal sinuses as an entity to
comprehend the diseases that affect this area. During the fourth week of gestation, the
frontonasal process can be identified with the maxillary and mandibular processes, all of
which eventually fuse to form the central facial structures (1). The frontonasal process,
which arises over the developing forebrain, is ectodermally derived and subsequently
contributes to the nasal capsule. The lateral wall of the nasal capsule enlarges over the
next few weeks, and shallow grooves begin to form within it.
By weeks nine and ten of gestation, approximately six ridges called ethmoturbinals or
basal lamellae are present on the lateral wall. These ridges are numbered in an anterior to
posterior direction (2). The first and second ethmoturbinals grow in the middle meatus,
which is covered medially by the developing middle turbinate. A portion of the first
ethmoturbinal remains to become the uncinate process, and part of the second
ethmoturbinal evolves into the anterior wall of the bulla ethmoidalis. Recognizable
furrows separate the ethmoturbinals, the furrow between the first and second
ethmoturbinals giving rise to the ethmoidal infundibulum. The third ethmoturbinal forms
the attachment of the middle turbinate to the lateral nasal wall, and the fourth
ethmoturbinal forms the attachment of the superior turbinate. The most superior
ethmoturbinals often coalesce and disappear by birth but occasionally remain to form a
supreme turbinate. The inferior turbinate is a separate entity and is not related to the
ethmoturbinals. The turbinates in their normal position on the lateral wall of the nose are
shown in Fig. 28.1.

FIGURE 28.1. Sagittal view of lateral nasal wall.



The maxillary sinus is the first of the paranasal sinuses to begin development in the
human fetus at around the sixty-fifth day of gestation as an outgrowth of the lateral wall
of the nose in the area of the ethmoid infundibulum between the first and second
ethmoturbinals (3). The sinuses slowly enlarge in utero to have average newborn
dimensions of 7 4 4 mm (length height width) (4). The maxillary sinuses are not
evident on plain radiographs until the infant is 4 to 5 months of age because they are
usually filled with fluid at birth. Growth of these sinuses is biphasic. The first period of
considerable enlargement occurs during the first 3 years of life. A second phase of
growth acceleration occurs between 7 and 12 years of age (4). During this second phase,
pneumatization extends laterally to the level of the lateral wall of the orbit and inferiorly
into the alveolar process in conjunction with eruption of permanent dentition. Slow
expansion of the sinuses occurs until 18 years of age to reach adult dimensions of 34 33
23 mm with an average capacity of 14.75 mL (4,5).
The ethmoidal cells are next to begin development later in the third fetal month (6). The
anterior ethmoidal cells form first as evaginations of the lateral nasal wall in the middle
meatus along the course of the evolving ethmoid infundibulum. Later in the fourth fetal
month, the posterior ethmoidal cells develop from outgrowths in the superior meatus (3).
These cells enlarge gradually in utero to reach a size of 2 4 2 mm for the anterior
group and 4 5 2 mm for the posterior group at birth (4). At birth these cells, which
usually number three or four, are fluid-filled and difficult to see on routine radiographs.
However, they can be seen on radiographs at 1 year of age and thereafter enlarge rapidly
to reach adult dimensions by 12 years of age. The anterior group measures 20 22 10
mm, and the posterior group measures 20 20 10 mm with an average total volume of
14 to 15 mL (5). During adolescence, ethmoidal cell pneumatization may extend to
several of the adjacent bones, such as the frontal or lacrimal bone, but the degree of
pneumatization may be variable from person to person.
The frontal sinus begins development during the fourth month of gestation as upward
extension of the most anterosuperior ethmoidal cells in an area termed the frontal recess
(7). The frontal sinus rarely is visible on radiographs earlier than the second year of life.
The sinus invades the frontal bone by about 5 years of age and slowly grows to reach an
adult size in late adolescence of 17 28 27 mm with a volume of 6 to 7 mL (8).
Pneumatization of the frontal sinus also is variable. In 4% to 15% of the population, a
developmental failure of one of the frontal sinuses is present (8).
The sphenoidal sinuses originate during the fourth fetal month as paired evaginations of
the mucosa in the superoposterior portion of the nasal cavity also known as the
sphenoethmoidal recess. They remain as small indentations on the sphenoid bone until 3
years of age, when further pneumatization begins. Growth becomes more rapid to reach
the level of the sella turcica by 7 years of age and an adult size of 23 20 17 mm with
a volume of 7.5 mL by 18 years of age (8,9). Pneumatization is once again rather
inconsistent, with possible extension into the greater wing of the sphenoid bone, the
palatine bone, and the base of skull.
ANATOMY
Ethmoidal Sinus
The ethmoidal sinus is by far the most complex paranasal sinus and has the greatest
variability of all the sinuses. This sinus, which also is called the ethmoidal labyrinth,
forms a pyramid on either side of the nose with the base located posteriorly. The sinus
measures approximately 4 to 5 cm in the anteroposterior direction, 2.5 cm in height, 0.5
cm in width anteriorly, and 1.5 cm in width posteriorly (10). The lateral wall of the
ethmoidal sinus is the lamina papyracea, which also serves as the paper thin medial
wall of the orbit. The medial wall of the sinus functions as the lateral wall of the nose. In
the midline of the nasal cavity lies the vertical plate of the ethmoid bone. This plate has a
superior portion in the anterior cranial fossa called the crista galli and an inferior portion
in the nasal cavity called the perpendicular plate of the ethmoid bone (Fig. 28.2). The
anterior cranial fossa is separated from the ethmoidal cells superiorly by the horizontal
plate of the ethmoid bone. The horizontal plate is composed of a thin medial portion
called the cribriform plate and a thicker, more lateral portion called the fovea
ethmoidalis, which forms the roof of the ethmoid bone (Fig. 28.2).

FIGURE 28.2. Coronal view through maxillary sinuses.



The horizontal plate of the ethmoid bone varies depending on the position of the
cribriform plate with respect to the fovea ethmoidalis. The length of the lateral lamella,
the extremely thin lateral part of the cribriform plate (Fig. 28.2), differentiates into three
types. In type 1, the cribriform plate is located 1 to 3 mm below the fovea ethmoidalis,
making the lateral lamella short or nonexistent. In type 2, the distance is 4 to 7 mm. In
type 3, it is 8 to 16 mm. Thus the lateral lamella is lengthened with each configuration.
The anterior vertical attachment of the middle turbinate to the horizontal plate is depicted
in Fig. 28.2. It separates the horizontal part of the cribriform plate from the lateral lamella
and the fovea ethmoidalis. The attachment of the middle turbinate is vital to remember
during intranasal dissection (11). Dissecting lateral to the turbinate prevents entrance into
the horizontal part of the cribriform plate, and the presence of a Keros type 2 or 3
ethmoid roof should prompt extreme caution to avoid entering the anterior cranial fossa
through the bone of the lateral lamella.
The horizontal plate of the ethmoid bone has another weak area called the dome of the
ethmoid bone. This is the area where the anterior ethmoidal artery traverses the ethmoid
roof. It can be found by means of following the second ethmoturbinal remnant (anterior
face of the bulla ethmoidalis) to the ethmoid roof and examining a few millimeters
posterior to that point (11). Dissection in this area should be scrupulous to avoid entering
the anterior cranial fossa and to prevent rupture of the artery, which can cause orbital
hematoma.
The ethmoidal cells are divided into an anterior group that drains into the ethmoid
infundibulum of the middle meatus (Fig. 28.3) and a posterior group that drains into the
superior meatus (5). The sinus usually consists of 4 to 17 cells per side, with an average
of 9 cells (12). The configuration of the cells is not uniform from person to person, and
several classification schemes have been proposed. The Ritter classification, which is
most commonly used, is based on both the origin and drainage of the ethmoidal cells
(12). The most anterior cells, which originate from the anterosuperior growth of
ethmoidal cells into the frontal bone, are the frontal recess cells (0 to 4 cells). The cells
form the frontal sinus, supraorbital air cells, and other various anterior and superior
ethmoidal cells.

FIGURE 28.3. Sagittal view through ethmoidal sinuses
with middle turbinate removed.



The next most anterior ethmoidal cells are the infundibular cells (1 to 7 cells). These cells
are variable in location, the most consistent being the agger nasi cells, which extend
outside the ethmoid capsule. The agger nasi (Fig. 28.3) is a mound of tissue on the lateral
nasal wall that represents a superior remnant of the first ethmoturbinal, which is just
superior, lateral, and anterior to the attachment of the middle turbinate. Pneumatization of
this area produces agger nasi cells that drain into the most superior end of the ethmoid
infundibulum, which is otherwise known as the frontal recess.
The bullar cells (1 to 6 cells) constitute the next group of anterior ethmoidal cells. These
cells, which are consistent in location, exist in the middle meatus and form the bulla
ethmoidalis, which is a partial sphere (Fig. 28.2). The anterosuperior wall of the bulla
ethmoidalis faces the frontal recess, and if the wall does not reach the ethmoid roof, a
suprabullar recess exists (Fig. 28.2). The bullar cells drain into this area and into the rest
of the ethmoid infundibulum along its course. Therefore the ethmoid infundibulum
represents a three-dimensional cleft running anterosuperiorly to posteroinferiorly, and the
two-dimensional opening to this cleft is the hiatus semilunaris. The bulla ethmoidalis
borders the ethmoid infundibulum posteriorly and superiorly; the lateral wall of the nose
is lateral, and the uncinate process is anteromedial. The uncinate process (Fig. 28.3) is a
thin semilunar piece of bone that is a remnant of the first ethmoturbinal. The superior
edge usually is free (Fig. 28.2), but it can insert onto the lamina papyracea or the fovea
ethmoidalis and cause variation in drainage patterns (2). The uncinate process can
become pneumatized and obstruct drainage in the ethmoid infundibulum.
The structure of the middle turbinate must be clearly understood to comprehend the
anatomic relations of the ethmoidal sinus. At the anterior end, the turbinate attaches
superiorly to the horizontal plate of the ethmoid bone (Fig. 28.2). This anterior segment
becomes pneumatized in about 12% of the population to form a concha bullosa, which
can block drainage from the ethmoid infundibulum. Behind the bullar cells, the insertion
turns laterally to insert on the lamina papyracea (Fig. 28.4). This attachment, which lies
in the frontal plane, represents the third ethmoturbinal (also called the third basal
lamella) and is the dividing line between the anterior and posterior ethmoid cells.
Posterior to this lateral attachment, the insertion of the middle turbinate turns inferiorly to
become horizontal. A sinus lateralis or retrobullar recess exists if the posterior wall of the
bulla ethmoidalis does not contact the third basal lamella (Fig. 28.3, Fig. 28.4) (2).

FIGURE 28.4. Axial view shows the three-dimensional
structure of the middle turbinate.



The posterior ethmoid cells (1 to 7 cells) are posterior and superior to the third basal
lamella. Aside from pneumatizing the posterior ethmoid capsule, these cells can invade
the palatine, maxillary, middle turbinate, and sphenoid bones. An Onodi cell is a
posterior ethmoid cell that can pneumatize an area of the sphenoid bone superior and
lateral to the sphenoidal sinus in 9% to 12% of the population (12). This entity is
clinically important because the optic nerve and carotid artery can be exposed and injured
during dissection in this area. The posterior ethmoidal cells drain into the superior
meatus, the supreme meatus if one exists, and the sphenoethmoidal recess, which is the
area between the superior turbinate, the roof of the nose, and the nasal septum.
Maxillary Sinus
The maxillary sinus (antrum of Highmore) occupies the body of the maxilla in adults and
is the largest of the paranasal sinuses. It is generally pyramidal in shape, the base being
formed by the lateral wall of the nasal cavity and the apex directed laterally toward the
zygomatic process. The roof, which also functions as the floor of the orbit, is composed
of thin bone crossed in the central portion by the infraorbital nerve. This nerve is
dehiscent in 14% of the population and can be damaged during manipulation in this area
(13). A Haller cell, which is a pneumatization of the ethmoid complex into the roof of the
maxillary sinus, sometimes can be identified (Fig. 28.2). This is important because this
cell can grow to occlude the maxillary sinus or the ethmoid infundibulum. The anterior
wall corresponds to the canine fossa and separates the sinus from the cheek skin. The
posterior wall separates the sinus from the contents of the infratemporal and
pterygomaxillary fossae.
The floor of the sinus, which is half as wide as the roof, is formed by the alveolar process
of the maxilla. Although it lies 4 mm above the floor of the nasal cavity in children, it
ultimately lies 4 to 5 mm below the floor of the nasal cavity in adults. The first and
second molars are the two most commonly dehiscent teeth in the maxillary sinus at 2.2%
and 2.0% of persons, respectively (14). With extensive pneumatization, the third molar,
bicuspids, and canine teeth can be exposed in the maxillary sinus. Exposure of the tooth
roots places the neurovascular bundle of the teeth in danger during curettage of the sinus.
Infection of dehiscent tooth roots and subsequent removal of the tooth can cause an oral-
antral fistula.
The medial wall of the maxillary sinus is the lateral wall of the nose, and it contains the
main sinus ostium by which the maxillary sinus communicates with the ethmoid
infundibulum. The ostium is located in the superior aspect of the medial wall, usually in
the posterior half of the infundibulum an average of 9 mm posterior to the nasolacrimal
duct (14). The posterior edge of the ostium is continuous with the lamina papyracea of
the ethmoid bone, allowing this edge of the ostium to be a reliable lateral limit in
intranasal dissection. In 15% to 40% of cases, an accessory ostia is present, which is a
hole in the mucous membrane covering a bony dehiscence, also called a fontanelle (2).
The accessory ostia, which are uncommon in children, can be inferior and anterior to the
uncinate process or more commonly superior and posterior to the uncinate process above
the insertion of the inferior turbinate.
Frontal Sinus
The frontal sinus develops from anterosuperior ethmoidal cells in the area of the frontal
recess. The frontal recess (Fig. 28.3) is a complex structure that can take many different
forms (2). The middle turbinate functions as the medial wall, and the lamina papyracea
makes up most of the lateral wall. The posterior wall is the anterior face of the bulla
ethmoidalis (also known as the second basal lamella), and the agger nasi cells help to
form the anterior wall. If pneumatization of the bulla ethmoidalis and the agger nasi cells
is minimal, the frontal recess develops into a wide area. If pneumatization of these areas
is extensive, the frontal recess becomes narrow and appears tubular.
The structure of the frontal sinus can be quite variable from person to person. The height
varies between 5 and 66 mm, and the width ranges from 17 to 49 mm. An intrasinus
septum usually is present, and the distal borders of the sinus often spread to form an
irregular pattern, which makes mucosal removal difficult during frontal sinus obliteration.
The anterior wall is the strongest of the sinus walls and is twice as thick as the posterior
wall (13). Each sinus wall has an anterior and posterior table with intervening diplo,
although the diplo is minimal in the posterior wall. The posterior wall separates the
frontal sinus from the anterior cranial fossa. The floor of the sinus also functions as the
supraorbital roof, and the drainage ostium is located in the posteromedial portion of the
sinus floor. The frontal infundibulum is a more narrow area within the sinus that leads to
the ostium (2). The frontal sinus-ostium-frontal recess complex is shaped like an
hourglass. The size of the bottom half depends on the dimensions of the frontal recess.
Sphenoidal Sinus
The sphenoidal sinus usually is an asymmetrically paired structure divided by a deviated
intersinus septum. Congdon (15) classified the extent of pneumatization of the sinuses
into three types. The first type, described as conchal, exists when the posterior extent of
the sphenoidal sinus is well anterior to the sella turcica. Presellar pneumatization occurs
when the posterior wall of the sphenoidal sinus reaches the anterior face of the sella
turcica. Postsellar pneumatization is present when the sphenoidal sinus extends past the
level of the sella turcica to approach the pons posteriorly and allows the sella to make a
superior indentation in the sinus. These three types are present in 5%, 23.5%, and 67% of
the population respectively, the other 4.5% manifest as intermediates between the
conchal and presellar types.
The sphenoidal sinus can undergo extensive pneumatization with possible extension into
the vomer, palatine, and maxillary bones as well as the greater wing of the sphenoid
along with the pterygoid plates. The bony tubercle surrounding the optic nerve commonly
becomes pneumatized, producing anterosuperior indentation in the roof of almost every
sphenoidal sinus (Fig. 28.3) (16,17). The bony covering usually is less than 0.5 mm and
is dehiscent in about 4% of the population. External and lateral to the sphenoidal sinus is
the cavernous sinus, through which run many vital structures. Growth of the sphenoidal
sinus can place many of these structures in proximity. For example, the internal carotid
artery forms a prominence covered by thin bone in the lateral wall of the sphenoidal sinus
in about 90% of the population, and 7% of these vessels are dehiscent (16,17). The
maxillary branch of the trigeminal nerve and the vidian nerve produce bulges in the
sphenoidal sinus in 30% of the population. Extreme caution must be taken when
dissecting within the sphenoidal sinus.
Each sphenoidal sinus empties into the sphenoethmoidal recess through a small ostium.
This ostium, which measures 0.5 to 4 mm, is located 10 mm above the sinus floor, or 30
degrees above the floor of the nasal cavity (8). The ostium is almost always membranous,
the bony circumference being considerably larger than the orifice, as is common with the
maxillary sinus ostium.
PHYSIOLOGY
Sinus Epithelium
The mucosa of the paranasal sinuses is continuous with the nasal cavity and, although
much thinner, also is composed of pseudostratified ciliated columnar epithelium with
four basic cell types. First a ciliated columnar epithelial cell possesses 50 to 200 cilia per
cell, each of which measures about 6 mm long and 0.2 mm in diameter (18). Each cilium
contains the typical nine plus two arrangement of microtubule doublets with dynein arms
extending between peripheral doublets to provide motion. At body temperature, the cilia
beat 10 to 20 times a second in a coordinated manner (18). Nonciliated columnar cells
also exist, and these cells along with the ciliated cells possess microvilli that are 1.5 mm
in length and 0.08 mm in diameter (19). The microvilli help expand the surface area of
the epithelium to improve humidification and warming of air. The ciliated cells are
plentiful within the sinuses, but the concentration of nonciliated cells grows to 50% at the
sinus ostium (20). The third cell type is the basal cell, which can vary in size, shape, and
amount. They may be a primitive stem cell that can differentiate into other epithelial
cells. The goblet cells are the fourth category of epithelial cells. These cells may or may
not be covered with microvilli, and they produce thick mucus after stimulation by an
irritating substance. Under the basement membrane of the sinus mucosa, the lamina
propria is quite thin, and both serous and mucinous glands penetrate into this layer. These
glands are under the control of the parasympathetic nervous system to produce thick
mucus and the sympathetic nervous system to produce thin mucus. The concentration of
goblet cells and submucosal glands is much lower in the sinuses than in the nasal cavity,
but the maxillary sinus has a higher amount of goblet cells than do the other sinuses (21).
In comparing the sinuses, the density of submucosal glands is highest at the ostia of the
maxillary, sphenoid, and anterior ethmoidal sinuses.
Mucous Blanket
The mucous blanket is composed of two layers. The sol layer exists as thin, periciliary
fluid that allows the cilia to be mobile between strokes. The upper, or gel, layer is a thick
sheet of mucus that supplies an insertion point for the tips of the cilia. The microvilli
have a role in producing the sol layer, and the goblet cells and submucosal glands make
the gel layer. The mucous blanket is primarily composed of mucoglycoproteins, which
provide protection against low humidity and cold weather in addition to capturing foreign
substances and trapping bacteria (22). The mucous blanket contains other components
such as immunoglobulin A with its secretory piece, which inhibits the adherence of
bacteria to the epithelial surface. Immunoglobulin G and interferon, as well as other
inflammatory cells, are present in sinonasal secretions to provide an antiviral role. The
mucous blanket also contains lysozyme and lactoferrin, which are capable of disrupting
some bacteria.
Once the foreign particles or bacteria are trapped, the sinuses can effectively drain the
mucus through the mucociliary clearance system. The cilia propel the mucus at a rate of 3
to 25 mm/min toward the natural ostium of the ethmoidal cells and sphenoidal sinus (23).
The maxillary sinus has a star-shaped drainage pattern from the sinus floor superiorly to
the ostium (Fig. 28.5). The mucociliary transport of the frontal sinus sweeps in a circular
pattern beginning on the medial wall of the frontal recess, progressing toward the roof,
turning laterally, and finally curving downward and medially toward the sinus ostium.
Once sinus drainage has taken place, the mucus is swallowed and transported to the
stomach, where any acquired bacteria are destroyed.

FIGURE 28.5. Schematic depicts mucociliary transport
routes in the maxillary and frontal sinuses. In the
maxillary sinus, the transport leads from the floor of the
sinus toward the ostium. In the frontal sinus, the pathway
leads up the medial wall to the roof, then laterally and
finally back across the floor to the ostium medially.



The Ostiomeatal Complex
The anterior ethmoidal cells reside at a point in the ethmoidal infundibulum where
common drainage exists between these cells and the frontal and maxillary sinuses. Many
processes can block the anterior ethmoidal cells, including those affecting ciliary motion
such as temperature less than 18C, an excessively acidic or basic environment, or
primary ciliary abnormalities such as dynein arm defects (22). Production of an
inadequate mucous blanket, such as with dehydration or humidity less than 50%, causes
sinus obstruction because the periciliary layer becomes too thin to allow normal
movement of the cilia. Immunoglobulin deficiency in the mucus decreases infection-
fighting capability and can allow viruses to invade the mucosa, and the viruses directly
decrease ciliary motion (18).
When the mucosa of the paranasal sinuses becomes swollen and inflamed by any of the
aforementioned mechanisms, two opposing mucosal layers often come into direct
contact. Messerklinger (24) found that the touching of these mucosal surfaces disrupts
mucociliary clearance. These areas of direct mucosal contact are most likely to be present
in the narrow channels of the ethmoidal infundibulum and ethmoidal cell system. Any
event that occludes the anterior ethmoidal cells can cause mucosal inflammation
sufficient to occlude the maxillary or frontal sinuses or can allow spread of infection to
the maxillary or frontal sinuses from the ethmoidal infundibulum. This specific relation
between the anterior ethmoidal cells and ethmoidal infundibulum complex in the
pathogenesis of frontal and maxillary sinus disease led to the description of the area
known as the ostiomeatal complex (Fig. 28.6). Evidence now clearly exists that severe
sinus disease in the maxillary and frontal sinuses resolves when normal aeration and
mucociliary clearance are restored to the anterior ethmoidal cells (25).

FIGURE 28.6. Concept of the ostiomeatal complex
(shaded).



FUNCTION OF THE PARANASAL SINUSES
The clinical significance of the paranasal sinuses is well known to anyone who has had
acute or chronic sinusitis. The functional significance of this anatomic region, however,
remains largely unknown. The sinuses have been believed to play numerous roles, but no
substantive laboratory studies have confirmed any of these hypothetical functions.
Prevailing theories suggest that the paranasal sinuses perform the following functions:
Humidifying and warming inspired air
Assisting in regulation of intranasal pressure
Increasing the surface area of the olfactory membranes
Lightening the skull to maintain proper head balance or assist in flotation
Imparting resonance to the voice
Absorbing shock to the head
Contributing to facial growth
Existing as evolutionary remains of useless air spaces
The complete function of the paranasal sinuses is probably not described by a single
theory but is instead most likely a combination of several of the foregoing theories.

HIGHLIGHTS
The maxillary sinus is the first paranasal sinus to developat
about the sixty-fifth day of gestation; in adults the maxillary is
the largest of the paranasal sinuses.
The ethmoidal sinuses are next to developlater in the third
fetal month. With the maxillary sinuses, the ethmoidal sinuses
are the only sinus cavities large enough at birth to be of clinical
significance.
The cribriform plate, which is the extremely thin, medial
portion of the horizontal plate of the ethmoid bone, can lie in a
plane inferior to the more lateral fovea ethmoidalis. Extreme
caution is needed during intranasal dissection.
The ethmoidal infundibulum is a three-dimensional cleft
running from the frontal recess anterosuperiorly to the third
basal lamella posteroinferiorly, into which drain the anterior
ethmoidal cells and the maxillary sinus.
The maxillary sinus often contains dehiscent structures, such as
the infraorbital nerve in the roof and the molar and bicuspid
teeth in the floor, that can be damaged by sinus curettage.
The frontal recess can be a wide space or a narrow structure
depending on the pneumatization of the bulla ethmoidalis and
the agger nasi cells.
The sphenoidal sinus can contain several prominent
indentations in the superior and lateral walls, including the
optic nerve, carotid artery, maxillary branch of the trigeminal
nerve, and the vidian nerve, all of which can be dehiscent and
possibly damaged during dissection.
The mucosa of the paranasal sinuses is composed of ciliated
and nonciliated pseudostratified columnar epithelium
interspersed with goblet cells, which produce thick mucus in
response to irritation. Serous and mucinous glands are located
under the basement membrane and produce thick and thin
mucus in response to the autonomic nervous system.
The mucous blanket and the ciliated epithelium combine to
form the mucociliary system, which contains antimicrobial and
immunologic properties capable of preventing bacterial
superinfection of the sinuses.
Clear evidence exists that severe mucosal disease previously
considered irreversible in the maxillary and frontal sinuses
resolves when normal aeration and mucociliary clearance are
restored and when anterior ethmoidal sinus disease is
controlled.
CHAPTER REFERENCES
1. Hamilton WJ, Mossman HW. Human embryology, 4th ed. Baltimore: Williams & Wilkins, 1972.
2. Stammberger HR, Kennedy DW. Paranasal sinuses: anatomic terminology and nomenclature. The
Anatomic Terminology Group. Ann Otol Rhinol Laryngol 1995;167:716.
3. Libsera C, Laude M, Libsera JC. The pneumatization of the accessory cavities of the nasal fossae
during growth. Anat Clin 1981;2:265278.
4. Schaeffer JP. The nose, paranasal sinuses, nasolacrimal passageways, and olfactory organ in
man. New York: McGraw-Hill, 1920.
5. Ritter FN. The paranasal sinuses, 2nd ed. St. Louis: Mosby, 1978.
6. Kasper KA. Nasofrontal connections: a study based on one hundred consecutive dissections. Arch
Otolaryngol 1936;23:322343.
7. Van Alyea OE. Frontal cells: an anatomic study of these cells with consideration of their clinical
significance. Arch Otolaryngol 1941;34:1123.
8. Van Alyea OE. Nasal sinuses: an anatomic and clinical consideration, 2nd ed. Baltimore:
Williams & Wilkins, 1955.
9. Maresh MM. Paranasal sinuses from birth to late adolescence. Am J Dis Child 1940;60:5578.
10. Mosher HP. The surgical anatomy of the ethmoidal labyrinth. Ann Otol Rhinol Laryngol
1929;38:896901.
11. Becker SP. Applied anatomy of the paranasal sinuses with emphasis on endoscopic surgery. Ann
Otol Rhinol Laryngol 1994;103[Suppl 162]:132.
12. Van Alyea OE. Ethmoid labyrinth: anatomic study, with consideration of the clinical significance
of its structural characteristics. Arch Otolaryngol 1939;29:881902.
13. Donald PJ, Gluckman JL, Rice DH. The sinuses. New York: Raven Press, 1995.
14. Lang J. Clinical anatomy of the nose, nasal cavity, and paranasal sinuses. New York: Thieme
Medical Publishers, 1989.
15. Congdon ED. The distribution and mode of origin of septa and walls of the sphenoid sinus. Anat
Rec 1920;18:97116.
16. Sethi DS, Stanley RE, Pillay PK. Endoscopic anatomy of the sphenoid sinus and sella turcica. J
Laryngol Otol 1995;109:951955.
17. Fujii K, Chambers SM, Rhoton AL. Neurovascular relationships of the sphenoid sinus: a
microsurgical study. J Neurosurg 1979;59:2839.
18. Wanner A. Clinical aspects of mucociliary transport. Am Rev Respir Dis 1977;116:73125.
19. Petruson B, Hansson HA, Karlsson G. Structural and functional aspects of cells in the nasal
mucociliary system. Arch Otolaryngol 1984;110:576581.
20. Halama AR, Decreton S, Bijloos JM, et al. Density of epithelial cells in the normal human nose
and the paranasal sinus mucosa: a scanning electron microscopic study. Rhinology 1990;28:2532.
21. Tos M. Goblet cells and glands in the nose and paranasal sinuses. In: Proctor DF, Anderson I, eds.
The nose: upper airway physiology and the atmospheric environment pp. 155162. Amsterdam:
Elsevier, 1982.
22. Waguespack R. Mucociliary clearance patterns following endoscopic sinus surgery. Laryngoscope
1995;105[Suppl 71]:140.
23. Proctor DF. The mucociliary system. In: Proctor DF, Anderson I, eds. The nose: upper airway
physiology and the atmospheric environment pp. 352376. Amsterdam: Elsevier, 1982.
24. Messerklinger W. Endoscopy of the nose. Baltimore: Urban and Schwarzenberg, 1978.
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theory and diagnostic evaluation. Arch Otolaryngol 1985;3:576582.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

29 SINUS IMAGING
Head & Neck SurgeryOtolaryngology
29




SINUS IMAGING
BARBARA A. ZEIFER

B.A. Zeifer: Department of Radiology, New York Eye & Ear Infirmary, New York, New York;
Department of Radiology, Albert Einstein College of Medicine, Bronx, New York.


Inflammatory Disease and Polyposis
Acute Sinusitis
Chronic Sinusitis
Clinical Significance of Mucosal Thickening
Considerations for Endoscopic Sinus Surgery
Computer-Assisted Surgery
Granulomatous Sinusitis
Fungal Sinusitis
Retention Cysts
Polyposis
Mucocele
Neoplastic Disease
Benign Tumors of Soft-Tissue Origin
Malignant Tumors of Soft-Tissue Origin
Benign Tumors of Bony Origin
Malignant Tumors of Bony Origin
Conclusion
Chapter References
Imaging studies of the paranasal sinuses provide the otolaryngologist with invaluable
information. The role of the radiologist is to define anatomy, to describe the location and
extent of the abnormality, and to suggest a tissue diagnosis. Plain radiography, computed
tomography (CT), and magnetic resonance imaging (MRI) are readily available.
Plain radiography is of limited usefulness in sinonasal imaging. The presence or absence
of moderate to severe mucosal thickening and air-fluid levels can be ascertained for the
maxillary and frontal sinuses. Evaluation of the ethmoidal labyrinth is unreliable,
however, and subtle disease is not depicted at all.
Computed tomography is a well-established method for paranasal sinus imaging. It
produces excellent spatial resolution for both bone and soft-tissue structures far
exceeding that of plain radiography. Images are generated by means of detection of a
transmitted x-ray beam, and tissue contrast results from differences in electron density.
The images can be viewed at various window settings. The bone window is best for
evaluating bony structures; the soft-tissue window provides soft-tissue detail; and a
modified lung window maximizes mucosal detail while producing adequate visualization
of bony structures. Computed tomography is an essential investigational tool in the
evaluation of all sinonasal abnormalities and is a preoperative requirement for sinus
surgery.
Intravenous injection of a contrast agent is used to improve tissue contrast and specificity.
For CT, several iodinated preparations are available for use, including both ionic and
nonionic (lower osmolality) agents. The nonionic preparations, although more expensive,
are better tolerated by patients and are associated with a lower incidence of adverse
reactions. Intravenous contrast agents enhance normal vascular structures and accumulate
in abnormal tissues with increased vascularity. These changes are most pronounced when
a power injector is used to deliver a rapid bolus. This enhancement is particularly useful
for evaluating neoplastic disease and complicated inflammatory processes. Soft-tissue
(neoplastic or inflammatory) disease becomes enhanced, whereas retained secretions do
not.
Absolute contraindications to intravenous injection of contrast material include previous
adverse reaction and severe renal insufficiency, particularly with multiple myeloma,
diabetes mellitus, and concurrent use of therapeutic nephrotoxic agents. Relative
contraindications include atopy, asthma, mild renal insufficiency, advanced age,
dehydration, cardiac disease, and the use of -adrenergic blockers (1). An oral
hypoglycemic medication, metformin hydrochloride, has been associated with lactic
acidosis and acute renal failure after administration of iodinated contrast material,
according to the package insert. In imaging of patients considered at high risk of reaction
to a contrast agent, pretreatment with a two-dose regimen of 32 mg methylprednisolone
12 hours and 2 hours before injection of an ionic contrast agent decreases the severity of
all reactions.
Magnetic resonance imaging has become increasingly popular for the evaluation of head
and neck disease as image sharpness and spatial resolution have improved. As does CT,
MRI provides cross-sectional images of the body. Magnetic resonance images are
produced by means of detection and measurement of emitted energy after rapid pulsation
of a radiofrequency wave into a high-strength magnetic field (up to 1.5 Tesla). Therefore,
the findings are described in terms of the signal intensity of the various tissues. Four
physical properties of matter are responsible for producing tissue contrast during MRI
T1 and T2 relaxation times, proton density, and flow. Information about these properties
can be obtained in different ways by varying the rapidity of the radiofrequency
excitations and the timing of data measurement. A complete study entails production of
different imaging sequences in the three orthogonal planes. T1, proton density, and T2
sequences routinely are performed; other sequences are available for use in specific
situations.
Magnetic resonance imaging provides better soft-tissue contrast and tissue
characterization than does CT. Images can be produced directly in any anatomic plane
with the patient positioned supine, whereas CT is limited to the axial and coronal planes.
Direct coronal CT necessitates full extension of the neck, a position often poorly tolerated
by an ill patient. A good-quality MRI study requires complete cooperation from the
patient, however, because even minimal movement degrades the image. Large quantities
of dental amalgam interfere with image production during MRI. Normal cortical bone
produces no signal on MR images; the thin, bony plates of the midface are seen only
because of their investing mucosa. Dependence on these bony structures for definition of
spatial relations and anatomic orientation limits the utility of sinonasal MRI in some
situations. Magnetic resonance imaging should be performed in addition to initial CT in
the evaluation of soft-tissue masses, complicated inflammatory disease, and extension of
disease beyond the confines of the sinonasal cavity. Magnetic resonance imaging clearly
differentiates soft tissue from fluid and helps to differentiate neoplasia from
inflammatory disease. Magnetic resonance imaging is less useful than CT for the
evaluation of trauma, typical inflammatory disease, and delineation of the ostiomeatal
complex.
Although MRI is generally considered a safe, noninvasive imaging modality, for some
patients MRI examination involves risks and hazards. The most common contraindication
to MRI is the presence of a cardiac pacemaker. Persons with cochlear implants, pacer
wires, or Swan-Ganz catheters likewise cannot undergo MRI. A metallic intraocular
foreign body can deflect in the magnetic field and cause vitreal hemorrhage. Plain
radiography of the orbits is considered an adequate screening examination for metallic
foreign bodies. Particles too small to be detected with this method are considered unlikely
to pose any risk of injury (2). Metallic fragments in the spinal canal also can be
dangerous. Intracranial aneurysm clips are of concern because many are ferromagnetic
and deflect. Death due to intracranial hemorrhage has been reported; therefore any patient
with an aneurysm clip should not undergo MRI unless the type of clip is known to the
physician and the manufacturer states that it is nonferromagnetic. All vascular clips, heart
valve prostheses, and orthopedic implants are considered safe in a magnetic field, as are
intravascular implants at least 6 weeks after insertion.
Gadoliniumdiethylenetriamine pentaacetic acid, the intravenous contrast agent for MRI,
is safe and well tolerated, although there have been isolated reports of severe reactions,
including anaphylaxis. As do the iodinated agents used for CT, gadolinium accumulates
in tissues with increased vascularity, resulting in increased signal intensity (enhancement)
on T1-weighted images. Unlike the findings at CT, vascular structures with moderate to
high flow have complete lack of signal owing to the flow of blood through the section
during data acquisition. This phenomenon is called the flow void.
INFLAMMATORY DISEASE AND POLYPOSIS
Acute Sinusitis
On radiographs, thickening of sinus mucosa alone is specific for neither acute nor chronic
inflammatory change. Acutely edematous and hyperemic mucosa is seen as smooth or
irregular soft-tissue thickening within the affected sinus cavity. Edema of the nasal
turbinates can be associated with this condition; however, thickened turbinate mucosa can
represent the natural nasal cycle, and care must be taken not to misinterpret this finding.
The presence of an air-fluid level if there has been no recent antral lavage suggests acute
inflammation (Fig. 29.1). Bubbling and stranding within the fluid-filled sinus cavity may
be seen. Unilateral involvement usually indicates a bacterial or, less commonly, fungal
cause.

FIGURE 29.1. Coronal computed tomographic of a
patient with acute sinusitis. Patient is positioned supine.
Bilateral concha bullosa cells (CB) are opacified. The
nasal cavity is opacified by turbinate edema or secretions.
An air-fluid level with bubbles (arrowheads) is present in
the right antrum. Nasoantral window on the left (arrows)
contains adjacent fibrous or mucoid strands.



Chronic Sinusitis
After repeated bouts of acute sinusitis, chronic hypertrophic changes develop, but the
mucosal thickening alone cannot be differentiated from acute disease. Long-standing
chronic inflammatory disease can produce osteitic changes of the sinus walls that result
in bony thickening, a process most common in the sphenoidal sinus (Fig. 29.2). Bony
thickening can be a postoperative change most pronounced in the maxillary antrum after
Caldwell-Luc antrostomy and mucosal stripping. Less severe bone thickening can be seen
in the ethmoidal cavity after endoscopic sinus surgery. Bone erosion can occur with
chronic inflammatory disease and often is associated with polyposis. Erosion into the
retromaxillary space is extremely unusual and suggests the presence of neoplasia or a
mucocele.

FIGURE 29.2. Coronal computed tomographic scan of a
patient with chronic sinusitis. Marked osseous thickening
of the right sphenoidal sinus has been caused by long-
standing inflammation. Reactive bone surrounds but does
not obliterate the vidian canal (arrowhead).



Clinical Significance of Mucosal Thickening
Making a diagnosis from the finding of mucosal thickening on CT scans and MR images
without clinical information can be hazardous. The presence of incidental abnormalities
of the ethmoidal sinuses when there is no history of allergic or inflammatory sinusitis is
significant. Some degree of ethmoidal disease occurs among nearly 11% of patients
undergoing CT of the head for unrelated problems. Most of these patients have focal
disease localized to four or fewer ethmoid air cells. Magnetic resonance images
frequently show clinically insignificant mucosal thickening as well. This mucosal
thickening is not histologically specific. It can represent acutely edematous mucosa,
chronically hypertrophic mucosa, or granulation tissue. If the patient does not have
symptoms, such findings have no adverse consequences.
The anatomic configuration of the sphenoidal sinus and its neurovascular relations raise a
different set of issues. The optic nerve, cavernous sinus, and orbital apex are at risk in the
presence of sphenoidal sinusitis. Incidental sphenoidal sinusitis is not as common as
incidental ethmoidal disease. When sphenoidal sinusitis is identified on an imaging study,
the risk of optic complications should be considered. Nearly 25% of patients with severe
sphenoidal sinusitis have serious neuroophthalmic dysfunction.
CONSIDERATIONS FOR ENDOSCOPIC SINUS SURGERY
A patient with repetitive acute sinusitis or chronic sinus inflammation that is
incompletely eradicated after medical treatment poses a distinct clinical problem to the
otolaryngologist. This patient may be a candidate for functional transnasal endoscopic
sinus surgery, now a popular and widely accepted procedure. Patient selection for this
procedure entails a detailed clinical history, systematic nasal endoscopy, and direct
coronal CT. Interpretation of the CT scan must be tailored to the needs of the surgeon.
The focus is not so much on providing a list of anatomic regions where mucosal disease
is present but on delineating specific anatomic features and identifying patterns of disease
that suggest functional obstruction of central drainage pathways. The ostiomeatal
complex, the sphenoethmoid recess, and the frontal recess become the prime areas of
interest (Fig. 29.3, Fig. 29.4, Fig. 29.5). Complete or partial obstruction of these outlets
causes inflammatory changes in the associated sinus cavities. This obstruction often is
caused by a combination of congenital distortion and superimposed disease. It is the
combination of these processes that CT should define. The anatomic relations of the
sinuses and nose are well seen on coronal CT scans. The structures of the ostiomeatal
complex are best evaluated in this plane. The anatomic features of the frontal recess and
sphenoethmoidal recess are best evaluated by means of sagittal reformation of thin axial
images.

FIGURE 29.3. Coronal computed tomographic scan
shows normal ostiomeatal complex. Components of the
ostiomeatal complex are as follows: 1, bulla ethmoidalis;
2, uncinate plate; 3, infundibulum; 4, inner maxillary
sinus ostium; 5, middle turbinate; 6, middle nasal meatus;
*, hiatus semilunaris. The following are other important
landmarks on this image: 7, lamina papyracea; 8, crista
galli; 9, ethmoidal roof; 10, cribriform plate; 11, anterior
ethmoidal foramen; 12, maxillary antrum; 13, inferior turbinate.



FIGURE 29.4. Normal sphenoethmoidal recess (SER).
A: Coronal computed tomographic (CT) shows the SER
is a cleft between the posterior ethmoidal and the
sphenoidal sinuses. It is oriented in the coronal plane and
therefore is not sharply delineated on coronal CT scans.
B: Sagittal CT reformation, right side. Image in the
sagittal plane shows the SER more clearly. In this patient,
the left sphenoid is asymmetrically large and is above the
right sphenoidal sinus in this view. S, Sphenoidal sinus; PE, posterior ethmoidal sinus; A,
anterior ethmoidal sinus; arrowheads, SER; 1, inferior turbinate; 2, middle turbinate; 3,
superior turbinate; 4, maxillary antrum; arrows, basal lamella.



FIGURE 29.5. Sagittal computed tomographic
reformation shows frontal recess. The frontal ostium
produces the waist of the classic hourglass configuration.
Inferiorly, a large agger nasi cell bulges posteriorly to
severely narrow and distort the recess (arrows). FS,
Frontal sinus ostium; FR, frontal recess; AN, agger nasi;
L, lacrimal bone; CB, concha bullosa; m, middle nasal
meatus.



Many anatomic variations of the nose and paranasal sinuses can interfere with sinus
drainage and thus predispose a patient to sinusitis. Others alter expected anatomic norms,
potentially complicating a surgical procedure. Most of these variations can be identified
on coronal CT scans. They include the concha bullosa cell, septal deviation and spur,
lateral convexity of the middle turbinate, pneumatization and inversion of the uncinate
plate, prominent agger nasi cell, prominent ethmoidal bulla, and Haller cell (Fig. 29.6).
The anterior attachment of the uncinate plate can be visualized: its configuration affects
the surgical approach to the frontal recess (Fig. 29.7). Anomalies of the frontal recess
include large agger nasi and frontal bulla cells. Anomalies of the posterior ethmoidal
sinus include pneumatization of the palatine bone and extension of the ethmoid into the
sphenoid bone, producing an Onodi cell. Potential hazards can be identified
preoperatively, such as exposed optic nerves within the sphenoidal sinus, bony defects of
the parasphenoidal carotid canal, hypoplasia or aplasia of the maxillary antrum, and
antral septation.

FIGURE 29.6. Coronal computed tomographic scan
shows anatomic variants of the ostiomeatal complex. A:
Concha bullosa. A prominent concha bullosa is present
on the left with a right septal deviation and small spur (s).
A small Haller cell on the right (arrow) and bilateral
supraorbital ethmoid air cells (SOE) are evident. B:
Paradoxical turbinates. Both middle turbinates are
paradoxically curved with lateral convexities. C: Haller
cells. Large bilateral Haller cells (arrows) pneumatize the orbital floor and narrow the
infundibula, particularly on the left. The middle meatus is unusually narrow. Mucosal
disease is superimposed.



FIGURE 29.7. Anterior uncinate attachment. In this
example, the uncinate process has a horizontal attachment
to the neck of the middle turbinate (arrowheads). A
lateral attachment is more common.



COMPUTER-ASSISTED SURGERY
The advent of the helical, or spiral, CT has enabled scanning of broad anatomic areas in a
relatively short time with low radiation exposure. Helical CT is essentially one
continuous scan in which block or volume of information is acquired that can be
manipulated later in many different ways. One such reformation of these data is to slice
into the volume and produce a two-dimensional image in an anatomic plane other than
the scan plane. Computer-assisted surgery takes advantage of this technology and adds to
it three-dimensional spatial localization (3). The patient undergoes helical CT of the
entire midface in the axial plane with either a headset or fiducial markers in place,
depending on the type of equipment. The data are transferred to the computer in the
operating room. At surgery, the data set in the computer is matched or referenced to the
patient with the headset or the markers so that a probe placed into the sinonasal cavity is
located accurately in space and then indicated on the screen. The computer screen shows
the axial, sagittal, and coronal CT sections, the intersection of which corresponds to the
tip of the probe. Depth and precise location of instruments can be checked during the
surgical procedure. This technique is particularly useful in revision surgery and
management of severe polyposis, in which anatomic landmarks are limited.
GRANULOMATOUS SINUSITIS
Granulomatous disease affecting the nose and paranasal sinuses can be infectious or
noninfectious. Infectious diseases include actinomycosis, nocardiosis, blastomycosis,
tuberculosis, syphilis, rhinoscleroma, and leprosy. Noninfectious entities include
Wegener granulomatosis, sarcoidosis, and foreign-body reaction from beryllium,
chromate salts, and cocaine. All the granulomatous diseases are potentially destructive
and can erode both cartilage and bone. These entities have similar radiographic features.
Initially, nonspecific soft-tissue nodules are found along the nasal septum with marked
mucosal thickening and retained secretions. Perforation of the cartilaginous nasal septum
is the hallmark of this group of disorders. Destruction of the bony septum and sinus walls
occurs later as the disease progresses (Fig. 29.8).

FIGURE 29.8. Coronal computed tomographic scan
shows granulomatous disease. A large septal perforation
involves both bone and cartilage. The middle turbinates
are eroded. Circumferential soft-tissue thickening is
evident throughout the nasal cavity. Secondary
obstruction of the ostiomeatal complex, or ostiomeatal
unit with ethmoid opacification and antral fluid also is
evident. The patient used cocaine.



FUNGAL SINUSITIS
Fungal sinusitis can be categorized into four distinct entities based on the status of the
host immune systeminvasive fungal sinusitis in an immunosuppressed patient, chronic
indolent sinusitis or mycetoma in a patient with normal immune function, and allergic
fungal sinusitis in a patient with heightened immune function or atopy (4). Invasive
sinusitis associated with mucormycosis or aspergillosis is an acute, fulminant, destructive
disease marked by vascular invasion and necrosis. The patient has nonspecific
opacification of the sinus cavities early in the disease and later has bony destruction.
Orbital, cavernous sinus, and intracranial extension frequently complicates this disease.
Some patients with diabetes have chronic invasive mucormycosis. These patients have a
prolonged disease course that responds to surgical dbridement and antifungal
medication. Imaging studies reflect slowly progressive destruction with eventual
formation of a single wide sinonasal cavity.
Chronic indolent fungal sinusitis is rare in the United States. It is a slowly progressive,
tissue-invasive infection, typically unilateral and not responsive to antibiotics. Fluid
collections are rare in all forms of fungal disease and when present suggest bacterial
infection. Mycetoma is a noninvasive fungal ball. It causes complete or near-complete
opacification of a sinus cavity and can be associated with thickening of the sinus walls.
Mycetoma usually is hyperdense on CT scans and contains calcifications in 25% of cases.
Mycetoma is markedly hypointense at MRI regardless of the sequence used to acquire the
images.
Allergic fungal sinusitis, a hypersensitivity reaction to fungal antigens, typically occurs
among patients with atopy and nasal polyposis. Allergic fungal sinusitis can involve one
or many sinus cavities. On CT scans, the involved sinus contains a peripheral rim of low
density, edematous mucosa and complete opacification of the central cavity by
homogeneous high-attenuation material corresponding to thick allergic mucin. There are
often scattered flecks of calcific material. The sinus walls can be surprisingly expanded
and destroyed. The high-attenuation contents of a scan that is not contrast enhanced
enable the radiologist to exclude neoplasia. On T2-weighted MR images, mucin is
extremely hypointense, mimicking an aerated sinus cavity (Fig. 29.9).

FIGURE 29.9. Allergic fungal sinusitis. A: Axial
computed tomographic scan without contrast
enhancement shows severe telecanthus due to expansion
of the ethmoidal sinuses. Ethmoidal septations are
preserved. On other sections (not shown), there was more
pronounced thinning and dehiscence of bone. Sinus
contents are predominantly hyperdense. B: Coronal T2-
weighted magnetic resonance image shows each affected
air cell is remarkably low in signal intensity, as low as cortical bone and air. This findings
is caused by the absence of water molecules in the allergic mucin. Retained hyperintense
secretions are evident in the maxillary sinuses.



RETENTION CYSTS
Retention cysts are common and occur with chronic inflammatory sinus disease. Serous
cysts are submucosal collections of fluid. Mucous cysts form as a result of mucous gland
obstruction. These cysts cannot be differentiated from one another or from isolated
polyps on radiographs. They usually occur in the floor of the maxillary antrum but can be
present elsewhere. They are incidental findings in 10% of instances.
POLYPOSIS
Individual polyps are smoothly rounded or pedunculated soft-tissue masses in the nose
and sinus cavities. They can obstruct sinus drainage if they are near the ostium. Diffuse
sinonasal polyposis produces more pronounced opacification. The multiple, packed
polyps can exert pressure on adjacent bony structures and enlarge the involved cavity.
This expansile process is slow and gradual, so the bone has time to remodel around the
mass (Fig. 29.10A). Expansion and distortion occur, and the intersinus septations with are
fairly well preserved, a finding most frequent in the ethmoidal labyrinth. Nasal polyps
frequently cause expansion of the superior nasal fossa and sphenoethmoid recess that can
be easily identified on coronal CT scans. Polyposis often is associated with accumulation
of highly proteinaceous secretions. The polyps are low in density on CT scans,
hypointense on T1-weighted MR images, and hyperintense on T2-weighted MR images.
The secretions are hyperdense on CT scans, hyperintense on T1-weighted MR images,
and hypointense on T2-weighted images (Fig. 29.10B).

FIGURE 29.10. Coronal computed tomographic scan
shows polyposis. A: Nasoethmoidal polyposis has caused
unusual lateral expansion of the ethmoidal bulla and
lateral nasal walls, which protrude in a diverticulum-like
manner into the maxillary antra. Left, the uncinate plate is
wedged between the bulla and the neck of the inferior
turbinate (small arrow). There have been previous
Caldwell-Luc antrostomies (large arrows) and
ethmoidectomies. B: Image of a different patient shows typical peripheral low-density
polyps. High-density inspissated secretions insinuate between the polypoid densities.
There have been previous ethmoidectomies, uncinectomies, middle meatal antrostomies,
and partial turbinectomies.



Antrochoanal polyps have a distinct radiographic appearance. At CT, both the maxillary
sinus and the middle meatus are completely opacified by an edematous, hypodense polyp
that can extend posteriorly into the nasopharynx. The polyp is hyperintense on T2-
weighted MR images. The polyp most frequently extrudes through the lateral nasal wall
at the posterior nasal fontanelle behind the posterior attachment of the uncinate plate,
where normal lack of bone provides a path of least resistance. There usually is
radiographic evidence of a slowly expansile process and a partially intact, lateral nasal
wall that has been pushed medially. Less frequent routes to the nasal cavity include the
infundibulum and the nasal wall below the neck of the inferior turbinate.
MUCOCELE
Mucoceles can occur as obstructive complications of chronic sinus inflammation,
polyposis, trauma, surgery, or tumor. The frontal sinus is most commonly involved,
followed by the ethmoidal, maxillary, and sphenoidal sinuses. Radiographs show smooth,
rounded enlargement of a completely opacified sinus cavity or air cell. This sign indicates
the slow nature of the expansile process. The walls are thinned, often barely seen.
Maxillary mucoceles often have areas of bony thickening with other areas of thinning due
to severe chronic sinus inflammation and the expansile process. At CT, the mucocele
contents have low density and do not become enhanced. Intensity characteristics at MRI
vary with the protein content of the mucocele and the degree of hydration (Fig. 29.11).

FIGURE 29.11. Frontoethmoidal mucocele. A: Coronal
computed tomographic scan shows a well-defined cystic
mass that has expanded the air cell to such an extent that
the bony rim is barely visible. B: Sagittal T1-weighted
magnetic resonance image (MRI) shows contents are
hyperintense owing to dehydration and high protein
concentration of the mucocele contents. C: Coronal T2-
weighted MRI shows predominant high signal intensity
of fluid with a central mucoid concretion of low signal intensity. These are the classic
imaging features of mucocele.



NEOPLASTIC DISEASE
Tumors of the nose and paranasal sinuses are encountered far less often than
inflammatory disease and polyposis. Malignant disease of the nose and paranasal sinuses
accounts for less than 1% of all malignant lesions in the body and 3% of all head and
neck tumors. Cross-sectional imaging plays an integral role in the diagnostic evaluation
of these lesions. Computed tomography and MRI offer a range of information about
density, signal intensity, contrast enhancement, and mass effect that helps to differentiate
benign from malignant disease and tumor from secondary mucosal inflammation.
Magnetic resonance imaging is particularly useful, because nearly 95% of all sinonasal
tumors are low to intermediate in signal intensity during the T2-weighted sequence. This
allows differentiation from the high signal intensity of polyps, mucosal inflammation,
and retained secretions.
Findings at contrast-enhanced CT can suggest the diagnosis of neoplasm but do not
approach the specificity of MRI findings. The exception is in the evaluation of bone
lesions, in which CT shows the calcific and ossific components to better advantage. Both
CT and MRI give precise anatomic detail regarding tumor location, extension, and origin
that is critical in the determination of operability or in planning radiation therapy.
Magnetic resonance imaging has an advantage over CT because optimal imaging planes
can be selected to maximize the information obtained. Tumor extension into adjacent
sinuses or into the orbit, pterygopalatine fossa, infratemporal fossa, and the cranium must
be clearly defined.
The pattern of bony involvement is an important diagnostic point in the evaluation of
sinonasal tumors. Slow tumor growth causes gradual expansion of the sinus cavity and
allows progressive remodeling of bone. Aggressive lesions cause focal and irregular
destruction of bone. Squamous cell carcinoma almost never behaves as a slowly
expansile lesion associated with bone remodeling. Other malignant tumors, including
adenoid cystic carcinoma and melanoma, can do so. Thickening and sclerosis of a sinus
wall are unlikely to be caused by malignant disease unless preceded by chronic
inflammation.
BENIGN TUMORS OF SOFT-TISSUE ORIGIN
Nasal papilloma originates from mucosal epithelium and includes the inverted, fungiform
(exophytic or septal), and cylindric cell types. The last type is quite rare but is similar in
radiographic appearance to inverted papilloma. Inverted papilloma arises from the lateral
nasal wall near the middle turbinate (Fig. 29.12). Rare presentations include a sinus
cavity mass, bilateral masses, and multicentric lesions. The most common radiologic
appearance is a nasal mass that erodes the lateral nasal wall and extends into the
maxillary antrum. In later stages, invasion of any adjacent region can occur, most
commonly the ethmoidal labyrinth. The appearance of this tumor can be so aggressive
that malignancy is suspected. Curvilinear or irregular calcifications have been described
in more than half of these lesions. Magnetic resonance imaging shows heterogeneous
tumor tissue suggestive of inverted papilloma only because of the typical location. Bone
involvement is caused by pressure erosion rather than tumor infiltration. Actual tumor
invasion of bone occurs only with malignant transformation and occurs in about 13% of
cases. Imaging studies may not be helpful in detecting malignant change. Invasion of the
posterior antral wall is so rare, however, that this finding indicates either malignant
transformation or secondary mucocele. Fungiform papilloma arises from the nasal
septum, remains localized to the nasal cavity, and rarely requires radiographic evaluation.

FIGURE 29.12. Inverted papilloma. Axial computed
tomographic scan shows a soft-tissue mass opacifying the
nasal cavity and maxillary antrum with gross destruction
of the intervening lateral nasal wall. The scalloped
contour of the posterior-lateral antral wall with
curvilinear septations is characteristic of long-standing or
recurrent inverted papilloma.



Benign nonepithelial tumors include juvenile nasopharyngeal angiofibroma (JNA) and
neural tumors. In rare instances meningioma has arisen within the frontal sinus. Although
technically a lesion of the nasopharynx, JNA so often extends to involve the posterior
maxillary antrum that its inclusion in a sinus tumor category is warranted. Originating
near the sphenopalatine foramen, JNA invades the pterygopalatine fossa in 89% of cases
and from there expands to deform and destroy the posterior wall of the maxillary antrum
(Fig. 29.13). This pattern of tumor extension detaches the pterygoid plates from the body
of the sphenoid bone. JNA exhibits marked enhancement on both CT scans and MR
images after injection of contrast material. Magnetic resonance imaging shows flow voids
that correspond to feeding vessels within and around the tumor. Angiography shows a
characteristic dense tumor stain.

FIGURE 29.13. Axial computed tomographic scan after
contrast enhancement shows juvenile nasopharyngeal
angiofibroma. A bulky, enhancing mass lesion involves
the nasal cavity, nasopharynx, infratemporal fossa, and
maxillary antrum. Landmarks of the pterygopalatine fossa
are completely disrupted by tumor invasion. The
pterygoid process is floating within the tumor mass
(arrowhead), and the posterior antral wall is destroyed.
ITF, Infratemporal fossa; T, temporalis muscle; M, maxillary antrum; LPt, lateral
pterygoid muscle. (Courtesy of Terry Becker, MD.)



Neurogenic tumors (schwannoma, neurofibroma) arising in the paranasal sinuses tend to
be well circumscribed, slowly growing lesions associated with bone expansion and
remodeling. Central septations are destroyed. Although these tumors tend to be quite
homogeneous on both CT scans and MR images, they can contain sites of cystic
degeneration that produce areas of high signal intensity on T2-weighted MR images
atypical for sinonasal tumors (Fig. 29.14). Malignant degeneration is rare and is
associated with a more destructive process. Sarcomatous lesions are bulky, irregular, soft-
tissue tumors that cause rapid destruction of bony plates. They have no specific
radiographic features.

FIGURE 29.14. Melanotic schwannoma. A: Coronal
computed tomographic scan shows a homogeneous soft-
tissue mass with well-defined expansile borders.
Centrally, however, the turbinates and ethmoid septations
have been destroyed. B: Axial T2-weighted magnetic
resonance image shows the mass is heterogeneous and
contains numerous cystic areas. These areas of
hyperintensity on T2-weighted images represent cystic
necrosis and are signs of neural tumors and adenoid cystic carcinoma. Tumor prevents
drainage of the maxillary antrum, which contains mucosal thickening and central
desiccated secretions.



MALIGNANT TUMORS OF SOFT-TISSUE ORIGIN
Malignant mucosal tumors of the paranasal sinuses include those of epithelial and
nonepithelial origin. Epithelial tumors include squamous cell carcinoma, glandular
tumors, melanoma, and esthesioneuroblastoma. Nonepithelial tumors include lymphoma
and the various sarcomas. Squamous cell carcinoma is the most common of these tumors,
accounting for nearly 80% of malignant tumors of the sinuses. At CT, squamous cell
carcinoma is seen as an irregular, poorly marginated, grossly destructive soft-tissue mass
(Fig. 29.15). At MRI, squamous cell carcinoma is heterogeneous in signal intensity and
becomes irregularly enhanced with gadolinium injection. Glandular tumors constitute
10% of all malignant tumors of the sinuses, and most commonly occur in the antrum and
nose. The rare adenocarcinoma most commonly involves the ethmoidal sinus and has
been linked to inhalation of carcinogens.

FIGURE 29.15. Squamous cell carcinoma. A: Axial
computed tomographic scan shows a large soft-tissue
mass within the right maxillary antrum has produced
frank bone destruction without expansion or remodeling.
This indicates an aggressive growth pattern. B: Coronal
T2-weighted magnetic resonance image of a different
patient shows a heterogeneous tumor nearly filling the
right maxillary antrum. The tumor has destroyed the
lateral nasal wall above the inferior turbinate (t) and bulges into the nasal cavity.
Retained secretions form a hyperintense rim around the tumor. Irregular low-signal areas
became enhanced after gadolinium injection (not shown). Areas of extremely low signal
intensity represent hemorrhage (arrows). Left septal deviation with an osseous spur (s) is
evident.



The minor salivary gland tumors include adenoid cystic carcinoma and the less common
mucoepidermoid carcinoma. These lesions tend to grow more slowly than squamous cell
carcinoma and therefore are associated with bone expansion. These tumors can contain
areas of cystic necrosis with serous or mucous collections that produce a heterogeneous
or high signal intensity pattern on T2-weighted MR images. Adenoid cystic carcinoma is
known for its proclivity to perineural invasion, but squamous cell carcinoma and the
various forms of sarcoma also invade neural structures (5). Tumor progression along the
maxillary division of cranial nerve V is most common, but infraorbital, palatine, and
alveolar nerves can be involved. The tumor can extend to the pterygopalatine fossa and
Meckel cave. Computed tomography shows enlargement of the involved foramen and
associated masses in the cavernous sinuses and pterygopalatine fossa. Magnetic
resonance imaging shows enhancement of the nerve itself, even in the absence of
foraminal expansion, and therefore is more sensitive. Perineural tumor spread, however,
is not detectable on any imaging study.
Malignant melanoma arising from the mucous membranes of the head and neck is rare.
When involving the nose and paranasal sinuses, this tumor is most likely to arise from the
nasal septum and turbinates. At CT melanoma usually is seen as an enhancing soft-tissue
mass that expands, remodels, and often destroys bony plates. The more aggressive the
lesion, the more destructive it appears. Magnetic resonance imaging shows isointense,
enhancing tumor tissue that can contain areas of high signal intensity on T1-weighted
images that correspond to hemorrhage. This tumoral hemorrhage has a greater influence
on T1 and T2 relaxation times than does melanin.
Esthesioneuroblastoma, an uncommon tumor arising from the olfactory epithelium, has a
characteristic radiographic appearance. This lesion originates high in the nasal fossa and
initially enlarges slowly and unilaterally, allowing the bone to remodel around it. More
aggressive behavior commonly occurs later with gross intracranial extension through the
cribriform plate (Fig. 29.16). Tumoral calcification or hyperostosis of the anterior skull
base can be seen. Magnetic resonance imaging is far more sensitive in detecting
intracranial extension than is CT.

FIGURE 29.16. Esthesioneuroblastoma. A: Coronal
computed tomographic scan shows an aggressive lesion
centered at the anterior skull base that has expanded and
destroyed the ethmoidal labyrinth, eroded the ethmoid
roof, and extended into the anterior cranial fossa
(arrowheads). Hyperostosis of the ethmoidal roof is
evident on the left. (Courtesy of Terry Becker, MD.) B:
Contrast-enhanced coronal T1-weighted magnetic
resonance image of a different patient shows intracranial extension.



Non-Hodgkin lymphoma is the most common nonepithelial malignant neoplasm that
arises from the mucosa of the paranasal sinuses. It accounts for 8% of malignant tumors
of the paranasal sinuses (Fig. 29.17). Lymphoma manifests as a soft-tissue mass that is
intermediate in signal intensity on both T1- and T2-weighted MRI images. It typically
permeates the sinus walls and produces diminished density and thinning without gross
displacement. Expansion of the sinus cavity or frank bone destruction can occur.

FIGURE 29.17. Axial computed tomographic scan
shows lymphoma. The soft-tissue mass in the right
maxillary antrum has infiltrated across the bony margins
of the anterior maxilla and posterior antral wall. The
involved bony plates are thinned and irregular but not
displaced.



BENIGN TUMORS OF BONY ORIGIN
Benign bone tumors of the paranasal sinuses are of fibroosseous or of giant cell origin.
Fibroosseous lesions include osteoma, osteochondroma, ossifying fibroma, and fibrous
dysplasia. Giant cell lesions include giant cell granuloma and brown tumor. Osteoma, a
common lesion, is benign proliferation of mature bone. It occurs almost exclusively in
the head and neck, particularly in the frontal and ethmoidal sinuses. Compact osteoma
and ivory osteoma are seen as extremely dense, well-defined masses within the paranasal
sinuses (Fig. 29.18). Cancellous osteoma is variable in density on plain radiographs and
CT because of the presence of a fibrous component. They can even appear as a soft-tissue
density on plain radiographs, but CT shows the ossific character. Multiple osteomas of
the face and skull are one of the many manifestations of Gardner syndrome.
Osteochondroma can occur in the nose and paranasal sinuses. As in other locations, it is
heterogeneously calcified and is pedunculated.

FIGURE 29.18. Waters view of ivory osteoma shows a
dense, homogeneous, sharply defined bony mass in the
left frontal sinus that protrudes into the orbit.



Fibrous dysplasia has a wide range of radiographic appearances that depend on the
relative amounts of fibrous and osseous tissue within the lesion. Head and neck
involvement is quite common, occurring in 50% of cases of polyostotic and in 10% to
15% of cases of monostotic disease (6). Any sinus can be involved. These lesions are
nondestructive, causing thickening and enlargement of the involved bone, which often
maintains its original shape. Most lesions have a hazy ground-glass appearance (Fig.
29.19). Cystic and sclerotic lesions are less common. Lesions become more sclerotic with
age. The MRI appearance of fibrous dysplasia can be confusing. During T1 sequences,
signal intensity ranges from mildly hyperintense to hypointense. Mild-to-moderate
enhancement is common. On T2-weighted images, marked, homogeneous hypointensity
is seen throughout the lesion, with the exception of cystic areas. This finding confirms the
diagnosis.

FIGURE 29.19. Fibrous dysplasia. A: Coronal computed
tomographic scan shows distortion of several craniofacial
structures. The involved bones are enlarged and have a
smooth, featureless trabecular pattern, the most common
appearance of fibrous dysplasia. The inferior turbinate
has been partially excised. B: Axial T2-weighted
magnetic resonance image shows markedly diminished
signal intensity similar to that of medullary bone. MT,
Middle turbinate; E, ethmoidal labyrinth; F, orbital plate of the frontal bone; M, maxilla;
C, crista galli.



Ossifying fibroma is closely related to fibrous dysplasia and tends to involve the facial
bones. It typically has a greater soft-tissue component and a more aggressive appearance
than does fibrous dysplasia, but often the two cannot be differentiated. These lesions are
well-circumscribed, expansile masses that can be of homogeneous soft-tissue density,
densely sclerotic, or of mixed attenuation on CT scans.
Brown tumor of hyperparathyroidism is the most common giant cell lesion of the facial
bones (Fig. 29.20). These lesions produce unilocular or multilocular cystic, expansile
masses with well-defined margins. After treatment and healing, brown tumor becomes
quite dense. While often it cannot be differentiated from brown tumor; giant cell
granuloma can be an aggressive lesion, at times mimicking a malignant tumor. Giant cell
granuloma usually is located in the anterior aspect of the mandible or maxilla and
contains calcific, ossific, or osteoid components in 30% to 75% of cases.

FIGURE 29.20. Coronal computed tomographic scan
shows brown tumor secondary to hyperparathyroidism.
Several expansile lesions involve both maxillae and the
left orbital roof. These lesions are at various stages of
development. Some are cystic, some have central
calcifications, and one is predominantly sclerotic. The
patchy, sclerotic appearance of the hard palate and
alveolar ridge is evidence of secondary
hyperparathyroidism and renal osteodystrophy.



MALIGNANT TUMORS OF BONY ORIGIN
The most common malignant bone tumors of the paranasal sinuses are multiple myeloma,
osteogenic sarcoma, and chondrosarcoma. Ewing sarcoma and malignant fibrous
histiocytoma are rare. Plasma cell dyscrasia is most commonly associated with the
generalized bone disease of multiple myeloma. Solitary plasmacytoma of bone or
extraosseous plasmacytoma also can occur. Involvement of the paranasal sinuses is seen
as a soft-tissue mass that is expansile and well defined but locally destructive. These
tumors are associated with multiple lytic skeletal lesions in 85% of cases. Seven percent
of osteogenic sarcomas are said to occur in the jaw. These aggressive lesions often are
purely lytic but can be associated with either amorphous calcification or a sunburst
appearance of radiating periosteal new bone (Fig. 29.21). Without new bone formation,
the specific diagnosis of osteosarcoma is not suggested. Chondrosarcoma of the paranasal
sinuses is rare. Chondrosarcoma is a soft-tissue mass that usually contains amorphous,
popcorn calcifications (Fig. 29.22). The well-differentiated lesions can have a benign
radiographic appearance; more aggressive lesions are more destructive. These tumors are
not associated with the periosteal reaction that occurs with osteosarcoma.

FIGURE 29.21. Coronal computed tomographic scan
shows osteogenic sarcoma. An aggressive, destructive
soft-tissue mass involves the left maxillary antrum, nasal
cavity, infratemporal fossa, and orbit. The sunburst
pattern of periosteal new bone confirms the diagnosis of
osteogenic sarcoma but need not be present. Magnetic
resonance images (not shown) did not have this ossific
component.



FIGURE 29.22. Axial computed tomographic scans
shows chondrosarcoma. Expansile tumor is present in the
right maxillary antrum. Typical round and popcorn-
shaped densities represent chondral calcification.
(Courtesy of Terry Becker, MD.)



CONCLUSION
Imaging of the paranasal sinuses is dominated by CT. Magnetic resonance imaging is
used for additional evaluation of complicated inflammatory disease and neoplasia. The
spectrum of disease is broad, and all imaging features must be considered carefully along
with the clinical features to arrive at a useful differential diagnosis. Clear delineation of
anatomic relations, so critical for surgeons, is the focus of all imaging studies. Reports of
intraoperative CT and open MRI updating of the data used in three-dimensional surgical
navigation systems have suggested that these imaging techniques can be useful in
preventing iatrogenic complications. Although open MRI is useful (7), intraoperative CT
updating is not recommended when the advantages and disadvantages of the system are
weighed (8).

HIGHLIGHTS
Computed tomography is the most reliable and informative
imaging tool for evaluating the nose and paranasal sinuses.
Direct coronal CT is best for evaluating the ostiomeatal
complex; sagittal reformation of thin-section axial scans
delineates the frontal recess.
Magnetic resonance imaging is essential for tumor mapping
because of excellent tissue characterization and the ability to
differentiate neoplasms from retained secretions.
Patients with cardiac pacemakers cannot undergo MRI.
The presence of intrasinus fluid suggests the existence of acute
sinusitis. Sclerosis of sinus walls indicates chronic sinusitis. In
the absence of these findings, acute and chronic sinusitis cannot
be differentiated on any imaging study.
Allergic fungal sinusitis can be associated with severe
expansion of a sinus cavity due to accumulation of allergic
mucin. This material is extremely dense on CT scans and
hypointense on T2-weighted MR images.
Antrochoanal polyps usually extrude through the posterior nasal
fontanelle. Extension through the infundibulum or inferior nasal
wall can occur occasionally.
A mucocele can have any pattern of signal intensity on MR
images, reflecting the protein content and hydration of its
contents.
Inverted papilloma typically erodes the lateral nasal wall;
destruction or expansion of the posterior antral wall is rare.
Malignant perineural infiltration can be detected with CT as
foraminal expansion and with MRI as neural enhancement.
CHAPTER REFERENCES
1. Lang DM, Alpern MB, Visintainer PF, et al. Increased risk for anaphylactoid reaction from
contrast media in patients on -adrenergic blockers or with asthma. Ann Intern Med 1991;115:270.
2. Shellock FG, Kanal E. Screening patients before MR procedures. In: Magnetic resonance
bioeffects, safety, and patient management. New York: Raven Press; 1994:91.
3. Zinreich SJ, Tebo SA, Long DM. Frameless stereotaxic integration of CT imaging data: accuracy
and initial applications. Radiology 1993;188:735.
4. Corey JP, Delsupehe KG, Ferguson BJ. Allergic fungal sinusitis: allergic, infectious, or both?
Otolaryngol Head Neck Surg 1995;113:110.
5. Parker GD, Harnsberger HR. Clinical-radiologic issues in perineural tumor spread of malignant
diseases of the extracranial head and neck. Radiographics 1991;11:383.
6. Kumar R, Madewell JE, Lindell MM, et al. Fibrous lesions of bone. Radiographics 1990;10:237.
7. Moharir VM, Fried MP, Vernick DM, et al. Computer-assisted three-dimensional reconstruction
of head and neck tumors. Laryngoscope 1998;108:1592.
8. Cartellieri M, Vorbeck F. Endoscopic sinus surgery using intraoperative computed tomography
imaging for updating a three-dimensional navigation system. Laryngoscope 2000;110:292.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

30 RHINOSINUSITIS: CURRENT CONCEPTS AND MANAGEMENT
Head & Neck SurgeryOtolaryngology
30




RHINOSINUSITIS: CURRENT CONCEPTS AND
MANAGEMENT
A. DANIEL PINHEIRO
GEORGE W. FACER
EUGENE B. KERN

A.D. Pinheiro, G. W. Facer, and E.B. Kern: Department of Otorhinolaryngology, Mayo Clinic,
Rochester, Minnesota.

Anatomy and Physiology of the Sinuses
Pathophysiology
Local, Regional, and Systemic Causes of Rhinosinusitis
Predisposing Factors for Rhinosinusitis
Classification of Rhinosinusitis
Allergic Fungal Sinusitis
Symptoms
Physical Examination
Microbiology of Rhinosinusitis
Management
Surgical Management
Complications
Emergencies
New Directions in Rhinosinusitis
Conclusion
Chapter References
Rhinosinusitis is defined as any inflammation of the mucosal lining of the sinuses. The
most common inflammation of the paranasal sinuses and the nose is the common cold.
Various aspects of acute, subacute, and chronic suppurative bacterial rhinosinusitis are
discussed in this chapter, including predisposing factors, pathophysiologic mechanisms,
differential diagnosis, medical management, and complications.
Sinusitis is the most common health care problem in the United States. It affects more
than 31 million persons a year. Americans spent approximately $150 million in 1989 for
products recommended or prescribed by physicians for management of sinusitis. Acute
sinusitis rarely is limited to one sinus. The long-accepted concept that most of sinus
disease involves the maxillary sinus has been replaced by the concept that disease
primarily involves the ostiomeatal complex. Emphasis has been placed on early
recognition of predisposing factors in the development of sinusitis. The diagnosis of
acute sinusitis usually is not difficult; however, the diagnosis of chronic sinusitis may be
more challenging because it can masquerade as other conditions. Family practitioners,
pediatricians, pediatric allergists, and otorhinolaryngologists have become increasingly
aware of the possibility of sinusitis, especially among children. Advances in computed
tomography (CT) and nasal endoscopy have helped improve the understanding and
diagnosis of sinusitis (1,2 and 3).
ANATOMY AND PHYSIOLOGY OF THE SINUSES
The exact functions of the four paired paranasal sinuses are unknown. Some degree of
nasal sinus respirationmaxillary nasal breathingwas proved by Cottle. The function
of the sinuses includes dampening of sudden increased intranasal pressure, voice
resonance, possible participation in olfaction, and humidification of inspired air as well as
decreasing the weight of the skull. The maxillary and ethmoidal sinuses are present at
birth, whereas the sphenoidal and frontal sinuses appear by the second to third years of
life. Complete sinus development usually occurs by the eighteenth year of life. The
frontal sinus varies greatly in size and shape. The nasofrontal duct drains into the
frontoethmoidal recess in the middle meatus. Ten percent to 12% of adults have a
rudimentary frontal sinus or lack pneumatization of the frontal bone.
The ethmoidal sinus is the most developed sinus at birth. The cells in the medial wall of
the orbit in adults vary greatly in size and number. The ethmoidal sinus is separated from
the orbit by a very thin layer of bone, the lamina papyracea. Infections can readily
penetrate the thin bone and rapidly cause orbital complications. The anterior and middle
ethmoidal cells drain into the middle meatus, whereas the posterior cells drain into the
superior meatus. The ostia of the ethmoidal sinus are approximately 1 to 2 mm in
diameter.
The maxillary sinus usually is present at birth. The fully developed maxillary sinus is
pyramidal. The ostium drains through the membranous middle meatus. The average
diameter is 2.5 mm, with a cross-sectional area of approximately 5 to 6 mm
2
. One or
more accessory ostia frequently are present in the anterior middle meatus. The accessory
ostia, when present, are located in the infundibulum or the membranous region of the
medial sinus wall. The sphenoidal sinus begins to develop by the second or third year of
life and usually is completely pneumatized by the seventeenth or eighteenth year of life.
The sphenoidal sinus drains into the sphenoethmoidal recess.
The pertinent anatomic relations of the middle meatus are important to understanding the
concept of sinusitis. It is now known that in most instances maxillary sinusitis is caused
by disease in the ostiomeatal complex. Mucosal swelling and obstruction in this critical
area can disturb the function of the sinus, and the disturbance can cause serious disease
and symptoms (Fig. 30.1).

FIGURE 30.1. Anatomic features of the ostiomeatal
complex. The relation of the middle turbinate, uncinate
process, and middle meatus is evident.



PATHOPHYSIOLOGY
The pathophysiologic mechanism of sinus disease is related to three factorspatency of
the ostia, function of the cilia, and the quality of nasal secretions (Table 30.1). Alterations
in any one of these factors, alone or in combination, change the physiologic system and
cause sinusitis. Diminished patency of the sinus ostium prevents adequate sinus drainage.
Because of the ciliary clearance of mucus toward the natural ostium, ostial obstruction
causes fluid accumulation inside the sinus even if an opening is made in a more
dependent position in the sinus, such as an inferior meatal nasoantral window. In the
maxillary sinus, mucus is cleared against gravity toward the natural ostium. Obstruction
of the ostia causes sinus disease. Ostial obstruction can be caused by edema, nasal
polyps, and other structural factors, such as a prominent concha bullosa, presence of
Haller cells, septal deviation, and postoperative synechiae. Nasal polyps in a setting of
atopy or cystic fibrosis and edema caused by allergens or viral or bacterial infection can
cause ostial obstruction. Once the ostium is obstructed, local hypoxia develops inside the
sinus cavity. Hypooxygenation and ostial obstruction cause accumulation of secretions
inside the sinus and provide an ideal culture medium for bacteria (Fig. 30.2).

TABLE 30.1. PATHOPHYSIOLOGIC
CHARACTERISTICS OF SINUS DISEASE



FIGURE 30.2. Obstruction of the sinus ostium produces
hypoxia, ciliary dysfunction, and retention of secretions.



Cilia need a fluid medium in which to beat and function normally. Sinus and nasal
secretions are critical for normal function. The normal ciliary environment is composed
of a double layer of mucusa superficial viscid gel layer and an underlying serous or sol
layer. As in all of the upper airway, nasal mucus is produced by both the goblet cells
interspersed among the ciliated columnar cells of the nasal epithelium and by the
submucosal mucus-producing glands. Changes in mucus compositiondecreased
elasticity or increased viscosityalter the effectiveness of cilia in clearing intranasal and
intrasinus mucus. The sinus cavities, which are believed to be nearly sterile among
persons with normal immune function, accumulate fluid and bacteria, which can cause
disease. The composition of mucus can be altered by changes in water and electrolyte
transport, as in severe dehydration and in cystic fibrosis. Another important factor is
increased production of mucus, which can be caused by airway irritants or pollutants or
triggered by allergens or exposure to cold air. If the rate of production of mucus exceeds
the rate of clearance, mucus accumulates and can serve as a medium for bacterial growth.
Altered ciliary function causes accumulation of fluid and bacteria inside the sinus.
Ineffective ciliary clearance can be caused by slowed ciliary motility, loss of
metachronous coordination among cilia, or loss of ciliated cells from the nasal
epithelium. Slowed ciliary motility can be caused by a variety of insults, including cold
air, viral and bacterial ciliotoxins, cytokines, and other inflammatory mediators (4,5).
Impaired ciliary clearance can be congenital, as in primary ciliary dyskinesia, such as
Kartagener syndrome. Normal mucous clearance depends on the coordinated activity of
the entire population of ciliated cells. Impaired metachronous activity of the ciliated cells
results in impaired clearance. Fibrous bands of scar in the nasal epithelium can prevent
effective motion of the mucous blanket across the nasal epithelium. Ciliated cells can be
lost as a result of injury to the nasal epithelium by airway irritants or pollutants, surgery
(mucosal stripping, scarring), chronic disease, or virus- or bacteria-induced cell death.
Abnormally high intranasal airflow has been linked to loss of ciliated cells from the nasal
epithelium (4).
Studies of experimental sinusitis in animals have shown that in acute sinusitis the
ultrastructure of ciliated cells is disrupted. The early inflammatory response is
characterized by a predominance of leukocytes in the tissues. Perhaps in response to
mediators elaborated by leukocytes, squamous metaplasia and eventually fibrosis and
gland involution follow the initial acute phase. Disruption of ciliary clearance of mucus
and bacteria, ostial obstruction, and alteration of the rheologic properties of the mucus
cause infection. All of these factors alter sinus homeostasis and are predisposing factors
for sinus disease.
LOCAL, REGIONAL, AND SYSTEMIC CAUSES OF
RHINOSINUSITIS
Local predisposing causes of secondary bacterial invasion into the sinus are related to
impairment of mucociliary transport function. Inspiration of cold or dry air can alter
mucociliary transport function and cause sinus infection. Medications and drugs can
adversely affect mucociliary transport.
The main regional predisposing factor for suppurative sinusitis is apical dental infection.
There also can be local causes, such as initial nasal or midfacial trauma, which can alter
the anatomic configuration of the ostiomeatal complex. Mechanical obstruction can be
caused by septal abnormalities. Choanal atresia, which interferes with drainage of the
nose, can be an important predisposing factor. Edema due to upper respiratory tract
infection can obstruct the ostium of the sinus, and bacteria can gain entrance into the
sinus and produce suppurative sinusitis. Barotrauma (pressure changes) during air travel
or swimming and diving can produce edema of the sinus ostium. Swimming in
contaminated water also can allow bacteria into the nose and sinuses and produce
suppurative sinusitis. Nasal polyps, foreign bodies, or nasal packing can alter the
ventilation of the sinuses and produce sinusitis. Nasal tumors can be a predisposing factor
in the development of bacterial sinusitis. Immotile cilia syndrome or ciliary dyskinesia, a
congenital disorder that involves disorientation of the cilia and abnormalities of the
dynein arms, can produce sinusitis and bronchitis as a result of a loss of mucociliary
clearance.
PREDISPOSING FACTORS FOR RHINOSINUSITIS
Systemic factors predisposing to the development of rhinosinusitis are general
debilitating conditions such as malnutrition, long-term steroid therapy, uncontrolled
diabetes, blood dyscrasia, chemotherapy, and other factors that contribute to states of
metabolic depletion. For these reasons, nosocomial (hospital-acquired) sinusitis appears
to be prevalent in intensive care units. Critically ill patients have several risk factors that
predispose them to the development of sinus disease. Among regional causes is
obstruction caused by nasotracheal or nasogastric tubes, which appears to predispose
patients to sinus infection. Hypermetabolism, debilitation, multiple organ dysfunction,
and colonization of the upper gastrointestinal and respiratory tracts by enteric gram-
negative bacilli also are predisposing factors for infection. In the intensive care units,
there is probably a progression of sinus disease that starts with fluid accumulation in the
sinuses that is followed by bacterial colonization of the upper respiratory tract, including
the sinuses, and possibly infection. In this setting, sinusitis probably reflects concurrent
ongoing infection at other sites. In particular, when there is no radiographic or clinical
evidence to suggest intracranial sepsis, it is unlikely that sinusitis is the sole or primary
cause of fever or sepsis among critically ill patients.
Sinusitis can be a manifestation of serious immune deficiency, such as immunoglobulin
G (IgG) deficiency. Deficiencies should be considered in all cases of recurrent sinus
infection. Rhinosinusitis can occur as a manifestation of human immunodeficiency virus
(HIV) infection. It has been reported that at least 80% of patients with acquired
immunodeficiency syndrome (AIDS) have symptoms of sinusitis. These patients may be
predisposed to rhinosinusitis early in the disease course because of delayed mucociliary
transport (6). Among persons with HIV infection who do not have symptoms of AIDS,
the same organisms that cause disease among persons with normal immune function are
likely involved. However, Pseudomonas organisms have emerged as important pathogens
among these patients. As the disease progresses, the organisms involved in causing
sinusitis often are those that cause disease elsewhere among persons with suppressed
immune function, including microsporidia, cytomegalovirus, Aspergillus (invasive),
Histoplasma, Cryptococcus, and atypical mycobacteria. Non-Hodgkin lymphoma can
masquerade as sinusitis among patients with HIV infection and is included in the
differential diagnosis of chronic sinusitis among this patient population. Patients
undergoing bone marrow transplantation are another example of persons with suppressed
immune function among whom frequent sinus infections are likely. Among these
patients, invasive Aspergillus organisms have identified as important pathogens that can
cause potentially fatal disease.
CLASSIFICATION OF RHINOSINUSITIS
Rhinosinusitis is classified along the following five axes: (a) clinical presentation (acute,
subacute, chronic), (b) anatomic site of involvement (ethmoidal, maxillary, frontal,
sphenoidal), (c) organism (virus, bacterium, fungus), (d) presence of extrasinus
involvement (complicated, uncomplicated), and (e) modifying or aggravating factors,
such as atopy, immunosuppression (specify cause), or ostiomeatal obstruction (specify
cause). An example of this five-axis system to classify sinusitis is (a) chronic, (b) frontal,
(c) bacterial sinusitis (d) complicated by frontal bone osteomyelitis and (e) aggravated by
immunosuppression due to diabetes mellitus. Appropriate medical and surgical
management of infectious sinus disease depends on accurate knowledge of all of these
factors.
Clinically, acute rhinosinusitis is any condition in the sinus that lasts 1 day to 4 weeks.
Management of acute sinusitis is medical therapy; surgical intervention rarely is
necessary. Drainage of an infected sinus in the acute stage of disease may be indicated if
orbital or intracranial complications threaten. Subacute rhinosinusitis is a sinus infection
that lingers 4 weeks to 3 months. In subacute sinusitis, the inflammation usually still is
reversible. Medical management is indicated. Surgery rarely is necessary in the subacute
phase other than to correct any underlying predisposing factors.
Chronic rhinosinusitis is the term used when sinusitis has persisted longer than about 3
months. Chronic rhinosinusitis essentially results from acute sinusitis that is either
uncontrolled or has been inadequately managed. Inflammation has so damaged the
natural mechanisms that promote sinus drainage that the process is irreversible without
surgical intervention. Ostial patency must be restored surgically to allow clearance of
mucopus from the sinus. Sinus ventilation and drainage must be accomplished for
resolution of the symptoms of chronic rhinosinusitis.
Viral sinusitis most often follows viral rhinitis. It rarely necessitates treatment except in
immunosuppressed persons with persistent infection with a pathogen such as
cytomegalovirus. Previous viral rhinosinusitis can damage cilia as a result of the presence
of viral ciliotoxins and predispose to bacterial sinusitis. Fungal sinusitis can be invasive
or noninvasive. Noninvasive forms include mycetoma (a fungus ball growing inside an
affected sinus cavity) and allergic fungal sinusitis. Invasive forms include fulminant
fungal sinusitis, which has an acute presentation with rapid progression, usually affects
immunosuppressed persons, and can be fatal, and indolent fungal sinusitis, which affects
persons with normal immune function and has a chronic presentation.
Sinusitis is classified according to involved sinus or according to its complications or
lack thereof. The complications usually are orbital or intracranial encroachment of the
disease process. Modifying factors can predispose a patient to sinus infection or can
prevent complete resolution of infection. These factors include atopy,
immunosuppression, ciliary dyskinesia, and mechanical obstruction, among others.
Complete classification of sinusitis is essential to tailoring the treatment to the situation.
Acute sinusitis and chronic sinusitis are managed differently, as are frontal and maxillary
sinusitis. Fungal and bacterial pathogens are controlled differently, and complications of
sinus infection must be dealt with properly.
ALLERGIC FUNGAL SINUSITIS
Allergic fungal sinusitis (AFS) is a form of chronic sinusitis characterized by nasal
obstruction, sinus pain, rhinorrhea, and frequent orbital symptoms, usually proptosis.
Other symptoms include dizziness, anosmia, and exacerbation of asthma. Buildup of
mucus in AFS frequently causes bony erosion of the sinus wall, and both orbital and
intracranial extension have been reported despite the lack of fungal invasiveness
characteristic of this disease.
Allergic fungal sinusitis once was diagnosed after the patient had undergone multiple
surgical procedures with continued recrudescence of the symptoms after a short-lived
disease-free period. At operation, thick, viscid, brown to green mucus with a peanut
butterlike consistency usually is found. Histologic examination shows that this allergic
mucus contains sheets of eosinophils, Charcot-Leyden crystals, and occasional fungal
hyphae but that the tissues do not. Thus it is described as noninvasive. Because the fungi
in AFS are noninvasive, culture of biopsy material from the sinus walls is not likely to
grow the organism colonizing the sinus. Cultures of the allergic mucus or of sinus and
nasal washings are more likely to grow the causative organisms. The pathophysiologic of
AFS is an allergic reaction (Gell and Coombs type I and type III hypersensitivity) to a
fungus that colonizes the sinus cavities. The inflammatory reaction is composed
predominantly of eosinophils that secrete mediators, such as major basic protein and
eosinophilic cationic protein, that damage the ability of cilia to effectively clear mucus
from the nasal passages. The role of IgG and complement activation in AFS has yet to be
defined. Polyp formation always is associated with the chronic inflammation of AFS. The
polyps further impede mucus clearing by causing mechanical obstruction of the ostia.
Patients with AFS often have unilateral involvement of one or two sinuses. Computed
tomographic examination shows areas of hyperdensity in the opacified sinus cavities.
Erosion of the bony sinus wall is frequently encountered on CT scans. In the past the
erosion was uniformly attributed to invasion. Current theories are that this bony erosion is
caused by (a) osteolytic factors secreted by the fungi themselves, (b) cytokine-mediated
osteoclast activation, or (c) long-standing pressure on the sinus walls.
The following diagnostic criteria have been adapted from a set proposed by Bent and
Kuhn (7) for the diagnosis of AFS: (a) positive test results for or a history of fungal
atopy, (b) nasal polyposis, (c) CT scan showing hyperdense material in the sinus cavity
and possibly evidence of sinus wall erosion, (d) allergic mucus with histologic
documentation of eosinophilic preponderance, (e) identification of fungus by stain,
culture, enzyme-linked immunosorbent assay, or polymerase chain reaction in the sinus
cavity mucus, and (f) no histologic evidence of tissue invasion by the colonizing fungus.
Other characteristics of the disease are peripheral eosinophilia, increased total
concentration of immunoglobulin E (IgE), and presence of allergen-specific IgE.
Management of AFS consists of ethmoidectomy and middle meatal antrostomy with
extirpation of the allergic mucus and polypectomy followed by postoperative therapy
with a steroid spray and frequent saline nasal irrigation. Some otolaryngologists advocate
a perioperative course of systemic glucocorticoids for all patients with AFS. Patients with
recalcitrant disease may need revision ethmoidectomy and possibly inferior meatal
nasoantral windows to allow continued irrigation and cleansing of the maxillary sinus.
Despite previous reservations against the use of fungal antigen desensitization, the
limited data on immunotherapy support use of this measure in the management of AFS
(8). Systemic antifungal agents are of no benefit in the management of AFS because the
fungi are not invasive. Unless it is secreted into the sinus cavity, an antifungal drug has
no effect on a fungus colonizing the sinus. In theory, antifungals with the proper
spectrum of activity against the dematiaceous fungi involved in AFS could provide
clinical benefit if applied intranasally. A topical antifungal spray could then be used to
reduce or eliminate fungal colonization, thereby eliminating or reducing the antigen load.
Such studies are under way.
Future AFS research will likely be aimed at identifying critical antigens for the various
genera of fungi involved in AFS. These antigens can be used for immunotherapy and for
development of antibodies to allow detection of a particular species with techniques such
as enzyme-linked immunosorbent assay and radioallergosorbent testing. On the other
hand, there may be wide cross-reactivity between divergent fungal antigens. This implies
that desensitization with one set of antigens would suffice to confer immunoprotection
against all fungi involved in AFS.
Future clinical research efforts must elucidate the role of topically applied antifungals in
the management of AFS. The role of immunotherapy must be further investigated in
double-blind studies. Other agents, such as leukotriene and cytokine antagonists, must be
developed and tested for their ability to reduce inflammation and provide clinical relief of
symptoms. Meanwhile, systemic steroids will continue to be of value until treatments are
found that are equally efficacious but without the risk of untoward effects of prolonged
steroid therapy.
SYMPTOMS
The symptoms of bacterial rhinosinusitis are related to the location and duration (acute,
subacute, chronic) of sinus involvement. The most remarkable and common symptom of
acute suppurative rhinosinusitis is pain. This can be nasal or facial pain or headache.
Because many patients who report sinus headaches have no sinus abnormalities, other
causes of facial pain are included in the differential diagnosis, especially when the patient
has no physical signs of suppurative sinus disease.
Patients with acute rhinosinusitis have the protracted symptoms of a cold, such as nasal
obstruction and nasal discharge. Associated systemic symptoms are fever, malaise, and
lethargy. Symptoms of acute and chronic rhinosinusitis are differentiated in Table 30.2.
In acute rhinosinusitis, pain usually is present over the infected sinus. The pain can be
localized to either the frontal, ethmoidal, or maxillary sinus region. Ethmoidal pain
includes pain in the medial portion of the nose or the retroorbital area. Sphenoidal
sinusitis can manifest as vertex or bitemporal headaches. Patients with acute suppurative
sinusitis may have unilateral or bilateral mucopurulent greenish-yellow nasal discharge.
When a history of previous upper respiratory tract infection is a predisposing factor, both
sides can be involved, and systemic symptoms are common. The patient may have a
fever, lethargy, and malaise. Recurrent acute suppurative sinusitis is a special situation
and demands a careful search for a predisposing factor, which can be a local, regional, or
systemic factor or a combination of any of these factors.

TABLE 30.2. COMPARISON OF SYMPTOMS OF
ACUTE AND CHRONIC SUPPURATIVE
RHINOSINUSITIS



Patients with chronic rhinosinusitis usually have a mucopurulent discharge and symptoms
of mild nasal obstruction; pain and systemic symptoms are conspicuously absent. The
patient usually does not have a fever and does not report headache or facial pain
contrary to what has been emphasized in advertisements. Acute suppurative rhinosinusitis
can be superimposed on chronic sinus infection. Patients with acute maxillary sinusitis
may report dental pain, marked nasal airway obstruction, and nasal discharge. Because of
the location and proximity of the ostia of the maxillary, ethmoidal, and frontal sinuses in
the narrow region of the middle meatus in the ostiomeatal complex, infection can spread
readily from one sinus to another. The inflammatory process involving all of the sinuses
is known as pansinusitis. Patients may have symptoms referable to all involved sinuses.
Periorbital edema can be present when the ethmoidal, frontal, and maxillary sinuses are
involved individually or together because of the proximity of the sinuses to the eye. The
eye essentially is bounded on three sides by sinuses, so the eye can be involved in sinus
disease. Blindness can be a complication of sinusitis (Fig. 30.3). Sphenoidal and
ethmoidal sinusitis can produce occipital, vertex, or parietal pain, nasal and retroorbital
pain, and pain radiating into the neck or shoulder.

FIGURE 30.3. Drawing shows close relation of the
sinuses to the eye. 1, Maxillary sinus; 2, ethmoidal cells;
3, frontal sinus; 4, sphenoidal sinus. (From the Mayo
Foundation, with permission.)



The presentation of acute sinusitis among children differs from the presentation among
adults. Children are much less likely to report classic sinus headaches. Instead, the usual
presentation is a cold that has lasted for more than 7 to 10 days, daytime cough with
nocturnal exacerbation, mucopurulent nasal discharge, fetid breath, and low-grade fever.
PHYSICAL EXAMINATION
The diagnosis of rhinosinusitis is established through the history and physical
examination and is confirmed with the radiographic findings and culture results, when
culture is indicated. Findings of the nasal examination are carefully recorded. Anterior
rhinoscopy with good illumination is invaluable to study the anatomic features and
mucosa. Mucosal edema and erythema may be present, as may streaking of a
mucopurulent discharge. The area of the discharge is documented, which can help in
determining which sinus is involved. Any facial tenderness and its location is
documented. The frontal sinus area, medial orbital regions (ethmoidal sinuses), anterior
part of the face, and the gingival buccal sulcus (maxillary sinus) are examined by means
of palpation and percussion. The examiner looks for periorbital edema and, particularly
among children, malodorous breath. The nasopharynx is examined carefully for
adenoidal obstruction, tumor, choanal atresia, and postnasal purulent discharge. A
complete ear, nose, and throat examination must be performed because otitis media or
serous otitis media can occur with sinusitis.
Transillumination can be performed, although it is not reliable. Only the frontal and
maxillary sinuses can be transilluminated. Decreased transillumination can give the
examiner the false impression that the sinus is occluded by secretions or pus when the
decrease is actually caused by a hypoplasia of the frontal or contraction of the maxillary
sinus.
With nasal endoscopy, the physician can ascertain which sinus or sinuses are involved
and the presence of any local etiologic factors. Endoscopy can be performed with either a
rigid or flexible fiberoptic endoscope. The nasal examination is conducted before and
after topical decongestion (1% phenylephrine) to allow the examiner to see septal
deformities, the middle meatus, the middle and inferior turbinates, and any changes,
polyps, or tumors that may be present. After decongestion, a topical anesthetic (4%
lidocaine or 5% cocaine) can be used. We use 4% lidocaine with a nasal atomizer
followed by nasal endoscopy to examine almost all patients with nasal and sinus
problems (Fig. 30.4, Fig. 30.5, Fig. 30.6 and Fig. 30.7). (See also Color Plate 1, Color
Plate 2, Color Plate 3 and Color Plate 4 following p. 370.) Sinuscopy with culture,
biopsy, or lavage can be accomplished through an anterior maxillary puncture under local
infiltration anesthesia (2 mL 1% lidocaine) or by means of insertion of an endoscope
through an inferior meatal puncture or previously made antral window.

FIGURE 30.4. Rigid Storz endoscopes with 0, 30, and
70 objective lenses. (See also Color Plate 1 following p.
370.)



FIGURE 30.5. Endoscopic view of left nasal cavity
shows septal deviation toward the middle turbinate and
middle meatus. (See also Color Plate 2 following p. 370.)



FIGURE 30.6. Endoscopic view of right middle meatus
shows purulent secretions due to acute sinusitis. (See also
Color Plate 3 following p. 370.)



FIGURE 30.7. Endoscopic view of polyps in the left
middle meatus. (See also Color Plate 4 following p. 370.)



Ultrasonography instead of repeated radiographs can be helpful in following the
resolution of acute suppurative sinusitis. Radiographic studies are helpful in confirming
the diagnosis. Plain radiographs of the sinuses are helpful in the evaluation of acute
suppurative sinusitismore so for the maxillary than for the ethmoidal sinuses; however,
CT has dramatically improved the ability to evaluate the anatomic relations and
abnormalities of the ostiomeatal complex and the extent of sinus involvement. The
possible radiographic changes of acute suppurative sinusitis are thickened sinus mucosal
membrane, an air-fluid level, or complete opacification of the sinus or sinuses involved.
Nasal polyps can be associated with sinusitis, or there can be discrete polypoid
involvement in any of the sinuses, especially the ethmoidal and maxillary sinuses (Fig.
30.8, Fig. 30.9, Fig. 30.10 and Fig. 30.11). Radiography and CT of the sinuses help to
confirm the diagnosis of acute or chronic suppurative sinusitis, but the most important
information comes from listening, palpating, and looking, which includes nasal
endoscopy (Table 30.3). Computed tomography has become the standard test for
assessing chronic rhinosinusitis as attested by the emergence of several CT-based staging
systems. Results of one study (9) confirm the reliability of CT evaluation and the
consistency of the findings over time.

FIGURE 30.8. Plain sinus radiograph (Waters view)
shows left pansinusitis of the maxillary, ethmoidal, and
frontal sinuses and sparing of the sphenoidal sinus.



FIGURE 30.9. Direct coronal computed tomographic
scan shows septal impaction into right middle meatus
without evidence of sinus disease.



FIGURE 30.10. Direct coronal computed tomographic
scan shows septal impaction into right middle meatus and
opacification of the left maxillary and anterior ethmoidal
sinuses.



FIGURE 30.11. Direct coronal computed tomographic
scan shows polypoid disease in both nasal posterior
fossae and the ethmoidal sinuses.



TABLE 30.3. DIAGNOSIS ACUTE
SUPPURATIVE RHINOSINUSITIS



MICROBIOLOGY OF RHINOSINUSITIS
Culture specimens obtained directly from the sinuses are more accurate than specimens
obtained from the nose, nasopharynx, and oropharynx. Numerous investigators have
shown that there usually is little correlation between culture results with specimens
obtained randomly from the nose or nasopharynx and those obtained by means of sinus
aspiration. Culture material can be obtained directly from the sinus by means of sinus
puncture and lavage or during surgical exploration. Because intranasal culture does not
adequately reflect the bacterial organism in the sinuses, antibiotic management of acute
sinusitis usually is empiric and based on the results of previous studies. There may be
more accurate correlation between culture results with specimens obtained by means of
endoscopy of the middle meatus and bacteria in the maxillary sinus (3).
The usual organisms that cause acute suppurative sinus-itis are similar in both adults and
children (Table 30.4). Most infections appear to be caused by Streptococcus pneumo-
niae, Haemophilus influenzae, Moraxella (formerly Branhamella) catarrhalis, and other
streptococcal species. Anaerobic bacteria sometimes are isolated from the maxillary sinus
during acute infection. Chronically infected sinuses in both adults and children usually
grow anaerobic bacteria with much greater frequency than do acutely infected sinuses. -
Hemolytic streptococci, Staphylococcus aureus, and H. influenzae also are common
pathogens. The type of organisms retrieved from chronically infected sinuses probably
depends on the type of antimicrobial therapy before culture. Chronic suppurative sinusitis
rarely if ever resolves with antibiotic management.

TABLE 30.4. MICROBIOLOGIC
CHARACTERISTICS OF SINUSITIS



Immunosuppressed patients, including those with AIDS, appear to be susceptible to
sinusitis. They are affected by the same organisms that cause disease among persons with
normal immune function. With increasing levels of immunosuppression, more atypical
pathogens are found (Table 30.4). Nosocomial sinusitis most often is polymicrobial and
usually is caused by the organisms most prevalent in an institution. Not uncommonly
they are the same enteric organisms that colonize the upper gastrointestinal and
respiratory tracts of critically ill patients (10). The exact organism and its antimicrobial
susceptibility reflect previous antimicrobial treatment.
When a patient is extremely ill, when there are systemic findings, or when the patient has
severe pain, it is prudent to obtain a culture directly from the involved sinus. When a
patient does not respond to empiric antibiotic therapy for acute suppurative sinusitis,
sinus culture must be considered. Sinus aspiration and culture are considered in the care
of immunosuppressed patients who do not respond to broad-spectrum antibiotics directed
against the usual organisms.
MANAGEMENT
Antibiotics are the keystone of medical management of acute suppurative sinusitis.
Amoxicillin is a good choice for first-line empiric therapy aimed at covering both gram-
positive and gram-negative organisms. Amoxicillin covers H. influenzae and M.
catarrhalis except strains that possess a -lactamase enzyme. It also covers S.
pneumoniae (pneumococcus) except strains that are highly resistant to penicillin because
of development of alterations in penicillin-binding proteins. Many strains of
pneumococci are intermediately resistant when tested in vitro, but they can still be
managed successfully with amoxicillin because the therapeutic blood level of the drug
usually exceeds the minimum inhibitory concentration determined for the organism in
vitro. Highly resistant S. pneumoniae is relatively rare in the United States, but if it
increases in frequency it can pose a serious resistance problem, because only vancomycin
covers the most resistant isolates. Other acceptable and inexpensive choices for first-line
ther-apy are a combination of erythromycin and a sulfonamide (erythromycin-
sulfisoxazole for children, erythromycin and trimethoprim-sulfamethoxazole for adults)
or cephalexin and a sulfonamide. Synthetic penicillin antibiotics with a -lactamase
inhibitor, such as amoxicillin-clavulanate and ampicillin-sulbactam, have a broader
spectrum of activity against -lactamaseproducing strains of H. influenzae and M.
catarrhalis, but they are not effective against penicillin-resistant pneumococci. Second-
generation cephalosporins cover -lactamaseproducing organisms.
In a multicenter, randomized, double-blind trial, investigators compared the safety and
efficacy of ciprofloxacin and clarithromycin in the treatment of 560 adults with acute
rhinosinusitis. The investigators reported that they observed clinical resolution or
improvement among 84% of the patients treated with ciprofloxacin and in 91% of those
treated with clarithromycin. However, twice as many relapses occurred among those
treated with clarithromycin (11).
When antibiotic treatment has failed or a patient has a history of frequent episodes of
recalcitrance to amoxicillin treatment, an antibiotic with a broader spectrum is chosen.
Amoxicillin-clavulanate is a reasonable choice. The incidence of diarrhea with
amoxicillin-clavulanate therapy can be decreased with a twice a day dosing regimen and
by prescribing yogurt for the duration of antibiotic therapy. Other acceptable choices are
clarithromycin and a second-generation cephalosporin, such as cefpodoxime, loracarbef,
cefuroxime, and cefprozil. Quinolones, such as ciprofloxacin, have been used to treat
adults with sinusitis. Use of these agents to treat children and women who may be
pregnant is precluded because of interference with cartilage development.
Parenteral antibiotics are used to treat patients with complicated infections, such as those
with orbital or intracranial extension of sinusitis. One factor to take into account for these
patients is antibiotic penetration of the blood-brain barrier. Ceftriaxone is a good choice
in such cases because in addition to covering all the relevant organisms, it has excellent
penetration of the blood-brain barrier. Other suitable parenteral agents are ampicillin-
sulbactam and similar agents. Anaerobic coverage can be provided with metronidazole,
which, unlike clindamycin has good penetration into the cerebrospinal fluid.
Nosocomial sinusitis is managed with parenteral antibiotics chosen on the basis of
specific culture and sensitivity data. The agents with the narrowest spectrum possible are
chosen to prevent the emergence of resistant organisms. However, before culture and
sensitivity data become available, the antimicrobial agents selected should cover gram-
positive and gram-negative organisms, including Pseudomonas and anaerobic bacteria.
Acceptable choices for initial broad coverage are metronida-zole plus ampicillin plus
either ceftazidime, cefotaxime, or ciprofloxacin. Imipenem and piperacillin-tazobactam
can be used as single agents in such situations, because they cover broadly gram-positive
and gram-negative organisms and anaerobic bacteria. If methicillin-resistant Staph.
aureus is strongly suspected, for example, it is isolated from another site such as tracheal
secretions, vancomycin is used. To prevent emergence of vancomycin-resistant
organisms, vancomycin is discontinued as soon as sensitivity results show the organism
is susceptible to an antistaphylococcal penicillin such as oxacillin. Therapeutic control of
Pseudomonas organisms usually mandates use of two agents acting in synergy to prevent
the emergence of resistant strains. Thus an aminoglycoside such as gentamicin or
tobramycin is added to an antipseudomonal penicillin, such as piperacillin, or an
antipseudomonal cephalosporin, such as ceftazidime.
Clinical improvement usually occurs within 48 to 72 hours of initiation of antimicrobial
therapy. Patients with a fever at the initial encounter return to normal temperature. The
discharge markedly decreases or subsides, and cough, particularly in children, is greatly
relieved.
Antibiotic therapy is continued for a minimum of 7 days after the symptoms have
disappeared. Treatment usually lasts a minimum of 10 days, and often lasts 3 weeks or
longer. Treatment for shorter periods can allow relapse, or the disease can progress to
chronic sinusitis. In addition to destroying the involved organisms, it is important to
decrease edema around the ostia to facilitate drainage and allow sinus oxygenation.
Topical and systemic decongestants are beneficial and facilitate oxygenation and sinus
drainage of pus by decreasing ostial mucosal edema. This is one of the few instances in
which topical decongestants, drops, or sprays are advocated and are beneficial, provided
that they are not used for more than 3 days.
We do not recommend antihistamines because they can produce further inspissation of
secretions and can cause substantial side effects. Antihistamines are considered only to
treat patients with allergy as the predisposing factor for sinusitis. Such patients can
benefit from immunotherapy directed against the allergens mediating chronic mucosal
inflammation and edema.
Analgesics are important for control of pain. Humidification can be useful, especially at
bedtime, and can be obtained with a steam or cold water humidifier. Mucolytics and
expectorants such as guaifenesin are helpful to some patients, especially when thick
secretions are a problem. Saline nasal irrigation is helpful to most patients who have a
large amount of nasal secretion. Medical drainage procedures such as Proetz
displacement can be used; however, we prefer decongestion and nasal sinus suction after
application of mild protein silver packs consisting of 50% protein silver solution. This is
especially useful 7 days after onset of acute infection. Treatment with protein silver packs
is painless and effective in removing pus from the sinuses and allowing oxygen to enter
during nasal breathing (Table 30.5).

TABLE 30.5. TREATMENT ACUTE
COMMUNITY-ACQUIRED RHINOSINUSITIS



Another valuable part of medical management of acute suppurative sinusitis is patient
education about the nature of the disorder and the plan of management. The patient needs
to understand that medical therapy is only part of treatment and that a surgical procedure
may be necessary, either in the office or in the operating room. The patient also needs to
understand that the physician is trying to ascertain the predisposing etiologic factors and
may have to obtain radiographs and blood tests or even perform a surgical procedure to
correctly diagnose or surgically repair any predisposing factor producing sinusitis.
SURGICAL MANAGEMENT
Surgical management can be performed to facilitate drainage of the involved sinus.
Surgical intervention may be urgent when complications are impending, when severe
pain has to be relieved, or when the patient is not responding to medical management.
The main indication for maxillary sinus irrigation is the presence of mucopurulent
material in an immunosuppressed patient or a patient with suspected subacute or chronic
maxillary sinusitis or acute sinusitis that has not responded to antibiotic therapy. The
main benefits of maxillary sinus irrigation are removal of mucopurulent material from the
involved sinus and facilitation of ventilation (oxygenation) of the sinus. If a maxillary
sinus is irrigated, the aspirate is cultured for bacteria, fungi, acid-fast bacilli, and
anaerobic bacteria. In rare instances, cytologic studies can be useful in diagnosing a
malignant lesion if a patient has unexplained unilateral maxillary sinus opacification. In
this situation, sinus irrigation can be therapeutic and can be helpful in establishing the
diagnosis. Every unexplained instance of unilateral sinus opacification must be taken
seriously and followed as if it were a malignant tumor until proved otherwise.
COMPLICATIONS
Complications can occur among patients with acute, subacute, or chronic sinusitis. The
rate of serious complications is low, but the precise incidence is unknown. Complications
usually are related to the local region of the involved sinus. Because the eye is
surrounded on three sides by sinuses, bacterial extension to the orbital contents can occur.
Orbital and periorbital complications include orbital cellulitis and subperiosteal and
orbital abscess. If the patient is not treated, these disorders can extend to the orbital apex
and cause blindness. Acute ethmoidal disease, especially among children, and frontal
sinus infection among adults can produce eye involvement early in the course of acute
disease. Infection of the sphenoidal sinus can cause vision changes because of the relation
between the sphenoidal sinus and the cavernous sinus, which is traversed by the
oculomotor (cranial nerve III), trochlear (cranial nerve IV), and abducent (cranial nerve
VI) nerves.
Osteomyelitis can involve the frontal bones or maxilla. Because of early treatment,
osteomyelitis is a rare complication of sinusitis in the western world. Oroantral fistulae
can be caused by dental problems and their management. Intracranial complications are
rare but can include epidural and subdural abscesses, meningitis, brain abscess, and
cavernous sinus thrombosis. Patients must be actively and aggressively treated if
complications are threatening to develop. Appropriate incision and drainage must be
considered early in these situations. Ophthalmologic or neurosurgical consultation is
obtained early, when sinusitis is virulent, the patient is debilitated, and complications are
impending.
The patient is informed that there are various steps in the management of acute, subacute,
and chronic sinusitis. Medical management is indicated mainly for acute and subacute
sinusitis and is successful in most instances. It may be necessary in a subacute phase to
consider minor surgical treatment. In most of these instances, surgery is curative. In the
chronic phase of sinusitis, surgical treatment may be indicated to reverse the disease and
ventilate (oxygenate) the infected sinuses. Surgery for acute maxillary sinusitis is
indicated if the pain persists for more than 24 to 48 hours despite appropriate antibiotic
therapy or if ophthalmic and neurologic complications occur (Table 30.6).

TABLE 30.6. COMPLICATIONS ACUTE
SUPPURATIVE RHINOSINUSITIS



EMERGENCIES
An emergency can occur in association with acute and subacute sinusitis and rarely with
acute sinusitis superimposed on chronic sinusitis. Surgical intervention may be necessary
for emergency relief of severe pain or prevention of impending complications. The most
common complication involves the eye because of its proximity to the sinuses. Orbital
complications usually necessitate immediate surgical evaluation and intervention, which
can include drainage of an abscess of the sinus. The ethmoidal sinus contributes to orbital
complications more often than do the other sinuses. To a lesser extent, the frontal and
sphenoidal sinuses can produce visual symptoms. Orbital complications, such as orbital
cellulitis, subperiosteal abscess, and orbital abscess, can extend to the orbital apex and
produce blindness. It may be necessary to consider emergency surgery to prevent serious
orbital complications. Third-nerve paresis can be caused by sphenoidal sinusitis and
necessitates immediate surgical drainage.
A patient with developing orbital cellulitis needs to be examined regularly by both an
otorhinolaryngologist and an ophthalmologist. If any change in extraocular eye
movement or decrease in visual acuity occurs, emergency surgical intervention is
performed.
Acute ethmoidal sinusitis with orbital complications that necessitate surgical intervention
is probably best managed through an external ethmoidectomy approach. If there are no
complications, it is reasonable to approach drainage of an ethmoidal abscess intranasally
and endoscopically.
Impending intracranial complications include epidural and subdural abscess, meningitis,
brain abscess, and cavernous sinus thrombosis. If any of these complications occurs, an
emergency has developed, and the patients must be actively and aggressively treated
surgically to drain the sinus responsible for the complications. Patients are examined and
observed by both an ophthalmologist and a neurosurgeon if ophthalmologic or neurologic
complications are developing or impending (Table 30.7).

TABLE 30.7. EMERGENCIES
RHINOSINUSITIS



NEW DIRECTIONS IN RHINOSINUSITIS
Because rhinosinusitis is diagnosed and managed by a variety of specialists and
disciplines, such as otolaryngologists, pediatricians, internists, family physicians,
allergists, and physician extenders, there is a great need for standardization of
terminology, diagnostic criteria, and treatment protocols. The American Academy of
OtolaryngologyHead and Neck Surgery Foundation has taken a leadership position in
this field with its rhinosinusitis task force. Periodic consensus reports and strong
educational programs to raise physician awareness have been initiated (12). The
rhinosinusitis task force and others have emphasized the importance of outcome studies
in efforts to define the disease and to increase the effectiveness of therapeutic
interventions (13,14).
CONCLUSION
Early diagnosis and early appropriate and aggressive medical (antibiotic, decongestant,
analgesic) therapy control acute suppurative sinusitis in almost all cases. The patient
needs to be informed that there are several steps in the management of acute and chronic
sinusitis. Aggressive management is indicated to decrease the incidence of complications
of sinusitis, which can be life threatening. Complications are considered an acute medical
or surgical emergency.
Much of the information available to practicing physicians concerning the medical
management of rhinosinusitis has come from the investigations and observations of
individual clinicians or small groups. Some of these studies have been criticized for poor
study design, author bias, commercial sponsor influence, and other factors. As we pursue
the standards of evidence-based management decisions, we are seeking the results of
larger multiinstitutional studies and reports that are endorsed by scientific societies and
public agencies (15,16).

HIGHLIGHTS
Rhinosinusitis is the most common health care problem in the
United States.
Acute sinusitis rarely is limited to one sinus, and the
pathophysiologic mechanism commonly involves the
ostiomeatal complex.
Emphasis is on early recognition of the predisposing factor in
the development of sinusitis along with early diagnosis so that
appropriate and aggressive medical therapy can be instituted
early to control acute suppurative sinusitis.
The three factors essential to normal function of the paranasal
sinuses are the patency of the sinus ostium, ciliary function, and
the quality of nasal glandular secretion. Alterations in any one
of these factors predispose a person to sinusitis.
Predisposing factors are local, regional, and systemic.
Rhinosinusitis is classified according to the following five axes:
(a) clinical presentation (acute, subacute, chronic), (b) sinus
involved (right or left ethmoidal, maxillary, frontal, or
sphenoidal; pansinusitis), (c) causative organism (viral,
bacterial, fungal, protozoan), (d) presence of complications
(uncomplicated or complicated by extrasinus extension), and
(e) modifying or aggravating factors, such as
immunosuppression or another predisposing factor. An
additional consideration is whether infection is community
acquired or hospital acquired, because the pathogens are
different.
The most common symptom of acute sinusitis is pain, which
can be nasal or facial, or a headache. Nasal obstructive
symptoms can occur.
Physical findings are nasal and facial tenderness, mucosal
edema and erythema, and gross mucopurulent nasal discharge.
Nasal endoscopy offers a distinct clinical advantage in
ascertaining which sinus or sinuses are involved in the acute
process.
The most common pathogens involved in acute suppurative
sinusitis are S. pneumoniae, H. influenzae, M. catarrhalis, and
other streptococcal organisms.
Allergic fungal sinusitis is an important cause of chronic
sinusitis characterized by (a) rhinorrhea in a setting of fungal
atopy, (b) nasal obstruction caused by polyposis, and (c) sinus
pain, headache, and orbital symptoms caused by accumulation
of allergic mucus within the affected sinuses. Management
includes endoscopic surgery, steroids (intranasal and possibly
systemic), and close follow-up care. The role of
immunotherapy in the management of AFS is controversial.
The most important management measure is antibiotic therapy
for a minimum of 7 days after all symptoms have disappeared.
Complications of rhinosinusitis are possible but infrequent and
necessitate aggressive medical and at times surgical
management.
CHAPTER REFERENCES
1. Lanza DC, Kennedy DW. Adult rhinosinusitis defined. Otolaryngol Head Neck Surg 1997;117:S1.
2. Lund VJ, Kennedy DW. Staging for rhinosinusitis. Otolaryngol Head Neck Surg 1997;117:S35.
3. Modlin JF, Naclerio RM. Microbiology of chronic sinusitis in children. Presented at the American
Society of Pediatric Otolaryngology, Toronto, May 18, 1990.
4. Waguespack R. Mucociliary clearance patterns following endoscopic sinus surgery. Laryngoscope
1995;105:140.
5. Norlander T, Westrin KM, Stierna P. The inflammatory response of the sinus and nasal mucosa
during sinusitis: implications for research and therapy. Acta Otolaryngol (Stockh)
1994;515[Suppl]:3844.
6. Milgrim LP, Rubin JS, Small CB. Mucociliary clearance abnormalities in the HIV-infected
patient: a precursor to acute sinusitis. Laryngoscope 1995;105:12021208.
7. Bent JP, Kuhn FA. Diagnosis of allergic fungal sinusitis. Otolaryngol Head Neck Surg
1994;111:580588.
8. Mabry RL, Manning SC, Mabry CS. Immunotherapy in the treatment of allergic fungal sinusitis.
Otolaryngol Head Neck Surg 1997;116:3135.
9. Bhattacharyya N. Test-retest reliability of computed tomography in the assessment of chronic
rhinosinusitis. Laryngoscope 1999;109:1055.
10. Bert F, Lambert-Zechovsky N. Microbiology of nosocomial sinusitis in intensive care unit
patients. J Infect 1995;31:58.
11. Clifford K, Huck W, Shan M, et al. Double-blind comparative trial of ciprofloxacin versus
clarithromycin in the treatment of acute bacterial sinusitis. Ann Otol Rhinol Laryngol
1999;108:360.
12. American Academy of OtolaryngologyHead and Neck Surgery, Report of the Rhinosinusitis
Task Force Committee, Otolaryngol Head Neck Surg 1997;117[Suppl]:S1S68.
13. Metson RB, Gliklich RE. Clinical outcomes in patients with chronic sinusitis. Laryngoscope
2000;110[Suppl 94]:2428.
14. Kennedy DW, Wright ED, Goldberg AN. Objective and subjective outcomes in surgery for
chronic sinusitis. Laryngoscope 2000;110[Suppl 94]:2931.
15. Brook I, Gooch WM III, Jenkins SG, et al. Medical management of acute bacterial sinusitis:
recommendations of a clinical advisory committee on pediatric and adult sinusitis. Ann Otol
Rhinol Laryngol 2000;109[Suppl 182]:120.
16. Anon J. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head
Neck Surg 2000;123[Suppl]:S1S32.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

31 SINUS SURGERY
Head & Neck SurgeryOtolaryngology
31




SINUS SURGERY
STEVEN D. SCHAEFER
RAY O. GUSTAFSON
STEPHEN F. BANSBERG

S.D. Schaefer: Department of Otolaryngology, New York Eye & Ear Infirmary, New York, New York.
R.O. Gustafson and S.F. Bansberg: Department of Otolaryngology, Mayo Clinic, Rochester, Minnesota.


Caldwell-Luc Operation
Indications
Technique
Complications
Intranasal Ethmoidectomy Without an Endoscope
Indications
Technique
Complications
External Ethmoidectomy
Indications
Technique
Complications
Transantral Ethmoidectomy
Indications
Technique and Complications
Chapter References
This chapter describes four external surgical approaches to inflammatory disease of the
maxillary and ethmoidal sinusesthe Caldwell-Luc operation, intranasal
ethmoidectomy, external ethmoidectomy, and transantral ethmoidectomy. Discussion of
sinusitis, functional endoscopic sinus surgery, surgical approaches to the frontal and
sphenoidal sinuses, and complications of paranasal sinus surgery are described in Chapter
25, Chapter 30, Chapter 32, Chapter 33, Chapter 34 and Chapter 35.
Acute and chronic inflammatory disease frequently involves more than one paranasal
sinus, so the operations often are performed in combination (Table 31.1). The critical role
of the anterior ethmoidal cells in the pathogenesis of maxillary and frontal sinusitis must
be kept in mind in surgical planning. Attention only to the secondarily involved maxillary
or frontal sinus can lead to failure because of persistent disease in the untreated ethmoidal
sinuses. Use of a thorough clinical history, comprehensive diagnostic nasal endoscopy,
high-resolution computed tomography (CT), aggressive medical therapy, and careful
patient selection maximizes the chances for a successful surgical outcome (Table 31.2,
Table 31.3). The patient needs to be counseled to understand that control, rather than
cure, of the disease is a realistic surgical goal.

TABLE 31.1. SURGICAL INDICATIONS



TABLE 31.2. DIAGNOSIS INFLAMMATORY
SINUS DISEASE



TABLE 31.3. TREATMENT INFLAMMATORY
DISEASE



CALDWELL-LUC OPERATION
The history of the Caldwell-Luc operation has been summarized by Macbeth (1) and is of
interest to all students of rhinology. In the last decade of the nineteenth century, both
Henri Luc of France and George Caldwell of the United States described the principle of
eradicating disease from the antrum and providing drainage into the nose. In the words of
Macbeth, It is likely that neither would recognize as theirs the operation we now do, but
I hope they would approve of it and the fact that we honor them by continuing to use their
names for an operation of high value (2).
Indications
With the acceptance of the principles espoused by Messerklinger as the foundation for
functional sinus surgery, the role of the Caldwell-Luc operation in the management of
sinusitis has been essentially replaced by intranasal ethmoidectomy with middle meatal
antrostomy (3,4,5,6,7 and 8). However, valid indications for the Caldwell-Luc operation
exist, including mycotic maxillary sinusitis (Fig. 31.1), multiseptate maxillary sinus
mucocele, antrochoanal polyp (Fig. 31.2), oroantral fistula closure, certain revision
procedures, such as recurrent maxillary sinusitis after intranasal ethmoidectomy and
middle meatal antrostomy, and preparation for transantral sphenoethmoidectomy, orbital
decompression, and exploration of the pterygomaxillary fossa. We consider eruption of
the permanent dentition a prerequisite for this procedure. In operations on pediatric
patients, intranasal ethmoidectomy with middle meatal antrostomy is our preferred
approach.

FIGURE 31.1. Coronal computed tomographic scan
shows left antral and intranasal mycotic mass. The
hyperdense focus (arrow) is characteristic of a fungal
process.



FIGURE 31.2. Coronal computed tomographic scan
shows (clockwise from upper left) antrochoanal polyp
filling the right antrum and entering the right nasal cavity
through an accessory ostium in the posterior fontanelle.



Technique
The operation is performed with local anesthesia by means of intravenous sedation or
with general anesthesia. When local anesthesia is used, the second division of the
trigeminal nerve is blocked with 1% lidocaine with 1:100,000 epinephrine (9). If general
anesthesia is used, the orotracheal tube is positioned in the contralateral oral commissure
or, in the case of bilateral surgery, the midline. Regardless of the type of anesthesia, the
nasal mucosa is atraumatically decongested with cottonoids moistened with topical
oxymetazoline solution. The superior buccogingival sulcus and the lateral wall of the
inferior meatus are infiltrated with 1% lidocaine with 1:100,000 epinephrine. Four
percent cocaine can be substituted for oxymetazoline when local anesthesia is used.

The incision extends from the canine to the second molar and is marked just above the
apex of the buccogingival sulcus (Fig. 31.3). This placement produces an excellent
inferior flap of soft tissue, facilitates closure, and is recommended for edentulous
patients. With the upper lip retracted superiorly and the ipsilateral oral commissure
retracted laterally, the mucosa, submucosa, and periosteum are incised with a cutting
cautery. The soft tissues are elevated superiorly in the subperiosteal plane for wide
exposure of the canine fossa. The infraorbital nerve is identified and carefully protected,
and the soft-tissue elevation is extended superiorly, both medially and laterally to the
nerve (Fig. 31.4).

FIGURE 31.3. Intraoperative view shows a proposed
right maxillary buccogingival incision.



FIGURE 31.4. Intraoperative view shows the facial
surface of the maxilla. The tip of the probe is adjacent to
the right infraorbital foramen.



Without traumatizing the infraorbital nerve, the retractors are repositioned to maximize
exposure, and the antrum is entered through the canine fossa with a mallet and gouge or a
cutting bur. The level of entrance is superior to the roots of the canine and premolar teeth.
Additional bone is removed from the facial surface of the maxilla with a sphenoid punch
and Kerrison rongeur to enhance exposure. The infraorbital foramen is preserved, but
additional bone can be removed superiorly, medially, and laterally to the nerve,
depending on the extent of disease. We recommend conservation of as much bone as
possible because the soft tissue of the face can collapse into the maxillotomy and obstruct
drainage of secretions distal to this site into the nose.
Topical application of 1:100,000 epinephrine to the antral mucosa enhances hemostasis
and facilitates inspection of the antrum (Fig. 31.5). We do not routinely strip or remove
the antral mucosa. The degree of mucosal instrumentation is conservative, dictated
strictly by the extent of irreversible disease. Normal-appearing mucosa is preserved,
especially in the region of the natural ostium, to facilitate restoration of normal
mucociliary clearance.

FIGURE 31.5. Intraoperative view through the right
canine fossa antrostomy shows the antral component of
an antrochoanal polyp.



When antral instrumentation has been completed, a nasoantral window can be made in
the central third of the inferior meatus. This procedure consists of infracture of the
inferior turbinate and construction of an inferiorly based mucoperiosteal flap, which is
turned down to the floor of the nose. The orifice of the nasolacrimal duct is protected.
The exposed bone is perforated with a punch, and the antrostomy is enlarged with a
Kerrison rongeur to correspond in size with the flap. The flap is turned over the inferior
aspect of the window into the antrum. The inferior turbinate is returned to its anatomic
position, and the inferior meatus can be loosely packed with antiseptic-impregnated
gauze or an antibiotic-covered Penrose drain, a loop of which is placed into the window.
Because inferior antrostomy does involve drainage from the maxillary sinus to the middle
meatus, we reserve this element of the procedure for patients with impaired mucociliary
flow that favors gravity drainage to the inferior meatus. In many cases of antrochoanal
polyps, the natural ostium has been so generously enlarged by the disease that an inferior
meatal window is unnecessary (Fig. 31.6). The wound in the buccogingival sulcus is
meticulously closed with a running lock stitch of 3-0 chromic catgut.

FIGURE 31.6. Intraoperative view shows the medial
wall of the right antrum after removal of an antrochoanal
polyp. The ostium is widely patent (arrow).



In the immediately postoperative period, the head of the bed is elevated 30 degrees, and
an ice pack is applied to the cheek to reduce edema. A broad-spectrum antibiotic is
administered perioperatively and is continued through the fourth postoperative day, when
the nasal pack is removed. In operations on many patients, we have found that meticulous
hemostasis has obviated packing. The use of a saline nasal spray several times a day is
advised to minimize crusting, and resumption of full activities is allowed after 1 week,
when the risk of bleeding has ceased.
Complications
In the immediately postoperative period, most patients have edema and ecchymosis of the
ipsilateral cheek (Table 31.4). Both these signs usually resolve rapidly, although among
patients with a bleeding diathesis or those who have been taking aspirin or
corticosteroids, the edema and ecchymosis can persist for several weeks. Most patients
have temporary dysesthesia in the distribution of the infraorbital nerve. This can be
persistent among as many as 30% of these patients (10). Although oroantral fistula and
epiphora from nasolacrimal duct trauma after the Caldwell-Luc operation have been
described, these complications can be prevented with meticulous surgical technique (11).
A final liability of the Caldwell-Luc procedure is the difficulty encountered in
interpretation of postoperative imaging studies. According to Noyek and Zinzmor (12)
and Cable et al. (13), antral opacification on postoperative plain radiographs is common
and occurs as a result of fibrosis and new bone formation. Although high-resolution CT
often is helpful, differentiating recurrent mucosal disease from postoperative changes can
be difficult. Antral contracture due to fibrosis and bony thickening of the antral walls can
make revision surgery difficult. Small fenestration of the anterior wall of the sinus
reduces the likelihood of this complication.

TABLE 31.4. COMPLICATIONS SURGICAL
PROCEDURES FOR SINUS DISEASE



INTRANASAL ETHMOIDECTOMY WITHOUT AN ENDOSCOPE
Yankauer (14) in 1923 described the technique of intranasal ethmoidectomy. Mosher's
(15) and Van Alyea's (16) detailed studies of the ethmoidal labyrinth further advanced
understanding of the surgical anatomy. Intranasal ethmoidectomy is used to control
disease within the primarily involved ethmoidal and the secondarily involved frontal,
maxillary, and sphenoidal sinuses. Failure to perform complete exenteration of the
anterior and posterior ethmoidal cells and sphenoidectomy, when indicated, is a frequent
cause of persistent paranasal sinus disease. Regional anatomic variation, anatomic
alteration, scarring from previous surgery, extensive sinus disease, and limited
visualization intraoperatively challenge the skills of the most experienced surgeon.
Indications
Intranasal ethmoidectomy is performed most often for nasal polyposis with hyperplastic
pansinusitis and recurrent suppurative sinusitis. Patients with steroid-dependent asthma,
aspirin sensitivity, and chronic sinusitis with nasal polyps respond variably to eradication
of the polyps and diseased sinus mucosa (17,18). However, patients with recurrent
suppurative sinusitis due to a structural abnormality, such as a concha bullosa, a
hypertrophic ethmoidal bulla, a paradoxically positioned middle turbinate, or a nasal
septal impaction, often can be cured with surgical correction of the abnormality and
eradication of the inflammatory sinus disease. Studies on the pathophysiologic
mechanism of recurrent sinus disease have resulted in a greater appreciation of the role of
the ethmoidal sinuses. We routinely open the anterior ethmoidal cells when performing
middle meatal antrostomy (4). Uncomplicated frontoethmoidal mucopyocele often can be
evacuated by means of intranasal ethmoidectomy. Isolated sphenoidal disease also can be
treated with this approach.

Technique
Intranasal ethmoidectomy can be performed with local anesthesia and intravenous
sedation or with general anesthesia. Binocular surgical loupes and brilliant headlight
illumination are essential for optimal intranasal perspective. The magnification and depth
perception provided by loupes enhances surgical orientation. An operating microscope
with a 300-mm lens and self-retaining nasal speculum is particularly helpful.
The patient is either fully supine or in the chaise-longue position to bring the plane of the
ethmoidal roof into a position close to parallel with the floor of the room. Topical
anesthesia and vasoconstriction are achieved by means of application of 4% cocaine on
cottonoids to the regions of the sphenopalatine ganglion and the ethmoidal nerves.
Cocaine is not to be used with general anesthesia because of the risk of cardiac
depression. One percent lidocaine with 1:100,000 epinephrine solution in a three-ring
syringe is injected into the region of the ethmoidal bulla, uncinate process, and the
anterior root of attachment of the middle turbinate. A 25-gauge spinal needle is
recommended to minimize trauma to the mucous membrane. The syringe is aspirated
before injection at each site to avoid intravascular injection. We recommend injection
before draping the patient to maximize the time for onset of vasoconstriction and
anesthesia. The eyes and the medial canthal regions are observed throughout the
procedure. Although with experience the surgeon begins to rely on proprioception, there
is no substitute for direct visualization in performing this procedure. This necessitates
absolute hemostasis and atraumatic technique.
The middle turbinate is displaced medially, and the uncinate process is incised with a
sickle knife and moved medially by means of subluxation. The uncinate process is
removed with a straight forceps, and the dissection proceeds posteriorly into the
ethmoidal bulla (Fig. 31.7). In cases of massive polyposis, the bulla can be expanded or
replaced by diseased mucosa. The suction tip can be used gently during anterior
ethmoidectomy to open the anterior ethmoidal cells and evacuate inspissated mucus and
debris. The anterior ethmoidal artery against the fovea ethmoidalis and the lamina
papyracea are identified as key landmarks and preserved. These regions are pain
sensitive, and a sedated patient can respond to palpation in this area.

FIGURE 31.7. Removal of the ethmoidal bulla. The
associations among the middle turbinate, ethmoidal cells,
anterior cranial fossa, and sphenoidal sinuses are evident.
The ethmoidal bulla and ethmoidal cells are lateral to the
middle turbinate. (Modified from Bill Westwood and the
Mayo Foundation, with permission.)



A straight forceps is used for exenteration of the disrupted ethmoidal cells in an anterior
to posterior direction through the basal lamella of the middle turbinate to the face of the
sphenoid. The residual superior cells are removed under direct vision with a curette in a
posterior to anterior direction to prevent penetration of the skull base. A superiorly angled
forceps or Kerrison rongeur is used to open the agger nasi cells (not the agger nasi, which
is the eminence at the anterior insertion of the middle turbinate) and clear disease from
the region of the frontal recess (Fig. 31.8). To assess patency, the frontal recess can be
palpated atraumatically with a curved suction tip or a probe. If there is no preoperative
evidence or intraoperative finding of frontal sinusitis, the frontal recess is not be
disturbed. The anterior attachment of the middle turbinate is not be disrupted, and normal
mucosa is meticulously preserved to avoid compromise of the frontal recess. Although
there can be polyps in the vault of the nose, we discourage instrumentation medial to the
attachment of the middle turbinate because the cribriform plate can be penetrated. We
also advocate preservation of the middle turbinate unless it is extensively involved with
polypoid disease. We have found that persistent pain and crusting appear to be more
common among patients who have undergone total resection of the middle turbinate.
Routine removal of the middle turbinate results in loss of an important landmark if future
surgery is needed.

FIGURE 31.8. Removal of agger nasi cells. Exenteration
of the posterior ethmoidal cells has been performed.
Cannulation of the nasofrontal duct is attempted.
(Modified from Bill Westwood and the Mayo
Foundation, with permission.)



When dissection is complete, the ethmoidal cavity is temporarily packed with a -inch
(1.25 cm) strip of gauze or cottonoids saturated with the solution of local anesthetic and
vasoconstrictor, and orbital tension is assessed by means of palpation. The gauze is
removed, and the ethmoidal cavity is again carefully inspected. Any residual diseased
mucosa and bone are removed, and the integrity of the lamina papyracea and fovea
ethmoidalis is verified. The middle turbinate is returned to its anatomic position, and the
ethmoidal cavity is gently packed with 1-cm gauze impregnated with a water-based
antiseptic ointment. Frequently used alternative ethmoidal cavity dressings include
polyvinyl acetal sponge, hydrogel sheets, polyglycolotic cream, and gelatin foam sheets
concentrically rolled and positioned between the lateral nasal wall and middle turbinate.
The dressing does not completely obstruct the nasal airway and is left in place for several
days to prevent scarring within the ethmoidal cavity and subsequent lateralization of the
middle turbinate. The surgeon minimizes any form of packing and secures the packing to
the face to avoid aspiration.
Visual acuity and extraocular movements are assessed in the immediately postoperative
period. A broad-spectrum antibiotic is administered until the nasal packing is removed on
the third or fourth postoperative day. Vigorous daily nasal irrigation with saline solution
is prescribed after dressing removal to minimize postoperative crusting. After dressing
removal, patients with nasal polyposis or hyperplastic pansinusitis resume use of a topical
intranasal steroid spray. The patient is seen once a week for 3 weeks for removal of blood
or crust and dbridement of foci of persistent disease from the cavity. Resumption of full
activity is allowed 1 week after surgery.
Complications
The rate of complications (Table 31.4) of intranasal ethmoidectomy decreases
considerably with increased surgical experience and proper magnification and
illumination (18,19 and 20). Minor complications include postoperative bleeding and
crusting, and these can persist for as long as 6 weeks postoperatively. Persistent epiphora
from injury to the nasolacrimal apparatus is an unusual but serious complication and can
necessitate dacryocystorhinostomy. Injury to the nasofrontal duct can cause postoperative
frontal sinusitis. Diplopia and blindness can be caused by orbital penetration. Horizontal
gaze diplopia is caused by trauma to the medial rectus muscle with subsequent fibrosis.
Blindness occurs after retrobulbar hemorrhage or direct injury to the optic nerve. Leakage
of cerebrospinal fluid and intracranial hemorrhage can occur if the fovea ethmoidalis or
cribriform plate is disrupted. These complications and their management are discussed in
Chapter 35, Chapter 36 and Chapter 37 (Table 31.5).

TABLE 31.5. EMERGENCIES ETHMOID
SINUS SURGERY



EXTERNAL ETHMOIDECTOMY
Despite the widespread interest in intranasal ethmoidectomy, external ethmoidectomy
remains an important option in the surgical management of chronic sinusitis. Many
surgeons believe this procedure provides the safest approach to the ethmoidal labyrinth,
and meticulous surgical technique usually produces an imperceptible facial scar.
Numerous modifications of the procedure have been advocated since the original
description by Ferris Smith in 1933 (21).
Indications
External ethmoidectomy often is used to gain simultaneous and wide access to the
ethmoidal and frontal sinuses (external frontoethmoidectomy) (22). This procedure also
is indicated for surgical treatment of patients with recurrent ethmoidal sinusitis whose
normal anatomic landmarks have been distorted by advanced disease or previous surgery.
The distortion can increase the risk of an intranasal procedure. External ethmoidectomy
also is used to manage acute ethmoidal or frontal sinusitis complicated by orbital or
periorbital abscess; biopsy of some orbital, ethmoidal, or frontal sinus lesions; and repair
of cerebrospinal fluid leaks originating from the cribriform plate or fovea ethmoidalis.
This approach can be combined with frontal craniotomy for en bloc removal of
neoplasms of the anterior base of the skull.
Technique
External ethmoidectomy usually is performed with general anesthesia. We mark an
incision that begins at the inferior margin of the medial aspect of the eyebrow, curves
down toward the medial canthus, and angles acutely back on to the side of the dorsum of
the nose, following a line dividing the dorsal and lateral subunits (Fig. 31.9). Hemostasis
is enhanced by means of infiltration of a solution of 1% lidocaine with 1:100,000
epinephrine into the soft tissues from the medial extent of the eyebrow to the side of the
dorsum of the nose. Decongestion and vasoconstriction are achieved for the nasal cavity
as described earlier, and the eyelids are carefully approximated to protect the globes.

FIGURE 31.9. External ethmoidectomy. A: Incision
placement. B: Exposure of the medial orbital wall. The
lacrimal sac is displaced laterally. C: Entrance into the
ethmoidal labyrinth.



The incision is deepened in layers through the skin, subcutaneous tissues, and
periosteum. The angular vessels are secured with bipolar cautery, and the supraorbital
bundle is preserved. Periosteal elevation proceeds both medially and laterally to facilitate
closure. Meticulous handling of the periosteum ensures the integrity of the medial canthal
ligament and the trochlea and allows atraumatic elevation of the lacrimal sac from its
fossa (Fig. 31.10).

FIGURE 31.10. Anatomic landmarks in the orbit. The
anterior and posterior ethmoidal arterial foramina lie in
the frontoethmoidal suture at the level of the anterior
cranial fossa.



Although the periosteum is initially densely adherent to the underlying bone, elevation
beyond the posterior lacrimal crest proceeds swiftly. As the medial wall of the orbit is
widely exposed, the anterior ethmoidal artery is encountered in the frontoethmoidal
suture line approximately 24 mm posterior to the anterior lacrimal crest (Fig. 31.11). This
vessel is clipped or electrocoagulated and divided. The periorbita is carefully protected
with a malleable retractor to prevent herniation of orbital fat into the field. Further
posterior periorbital elevation is not routinely performed. If additional elevation is
necessary, the posterior ethmoidal artery is encountered approximately 10 mm posterior
to the anterior artery and approximately 5 mm (range 1 to 8 mm) anterior to the optic
foramen (23). These proportions are not constant, and great care must be exercised in
ligation of the posterior ethmoidal artery.

FIGURE 31.11. Intraoperative view shows the medial
wall of the right orbit. The lacrimal fossa (curved arrow)
and anterior ethmoidal artery (straight arrow) are
evident.



The surgical field at this point widely exposes the lacrimal bone, frontal process of
maxilla, lamina papyracea, and orbital process of frontal bone. The ethmoid is entered
through the lacrimal fossa with a mallet and gouge or drill. The exposure is
circumferentially widened with a Kerrison rongeur. The frontoethmoidal suture is an
important landmark because it identifies the level of the anterior cranial fossa. The lamina
papyracea is taken down to allow complete exenteration of the ethmoidal cells. If
necessary, the frontal sinus is opened from below, and intranasal anterior ethmoidectomy
brings the ethmoidal cavity and middle meatus in continuity. We strongly advocate
preservation of the middle turbinate. However, if the middle turbinate is removed, care
must be taken to avoid disruption of the cribriform plate.
If the frontal sinus has been disrupted, a sheet of lightweight polymeric silicone can be
made into a tube and positioned in the cavity extending from the frontal sinus to the
anterior head of the inferior turbinate, where it is secured with a permanent suture. The
silicone is left in place for at least 6 weeks to produce a mucosa-lined track between the
frontal sinus and the middle meatus (24). Stenting does not solve the problem of
medialization of the soft parts of the orbit into the frontal recess after excessive removal
of the anterior bony orbit. Maximal bone preservation is preferable.
The nose is lightly packed with 1-cm petrolatum gauze or preformed surgical sponges
impregnated with water-based antiseptic ointment. The periosteum and subcutaneous
tissues are reapproximated with 3-0 chromic catgut sutures. Skin closure is accomplished
with 6-0 nylon or mild chromic catgut sutures, and an ice pack is applied. The patient is
given a broad-spectrum antibiotic during the postoperative period. The nasal packing is
removed on the third or fourth postoperative day. The sutures are removed on the fifth
postoperative day. The routine of postoperative nasal hygiene is the same as that
prescribed after intranasal ethmoidectomy.
Complications
The complications of external ethmoidectomy are the same as those of intranasal
ethmoidectomy (Table 31.4). However, the risk of orbital injury and intracranial
penetration is lower with the external approach. Inappropriate incision placement or poor
surgical technique can cause hypertrophic scar formation, medial canthal scarring, or
rounding of the medial canthus. Hypertrophic scar formation can be improved with a
running W-plasty or multiple Z-plasty scar revision technique. Anesthesia or hypesthesia
of the forehead can occur but usually subsides if the supraorbital nerve is intact. Injury to
the lacrimal apparatus is uncommon.
TRANSANTRAL ETHMOIDECTOMY
Another approach to the ethmoidal sinus is the transantral route. First described by Jansen
(25) in 1894, this procedure was popularized by Horgan (26) in 1926 and by
Langenbrunner and Nigri (27) in 1977.
Indications
The transantral approach provides direct access to the middle and posterior ethmoidal
cells, yet it is limited by poor exposure of the anterior ethmoidal cells and by the
attendant morbidity and potential complications of the Caldwell-Luc procedure. For these
reasons, we limit our use of the transantral approach primarily to transantral orbital
decompression (28,29) which also can be well performed endoscopically.
Technique and Complications
Proper positioning enhances surgical exposure. We place the table in the 15-degree
reverse Trendelenburg position. The initial details of the procedure, including the choice
of attended local or general anesthesia and canine fossa antrotomy, are identical to those
described for the Caldwell-Luc operation. Thorough removal of the facial surface of the
maxilla between the infraorbital foramen, the infraorbital rim, and the ascending process
of the maxilla is critical in achieving exposure of the floor of the orbit, the medial wall of
the antrum, and the ethmoidal cells. As in the Caldwell-Luc operation, antral mucosal
instrumentation is conservative and is dictated strictly by the extent of the disease.
After antral mucosal instrumentation is complete, a microscope with a 300-mm lens is
brought into the field to provide brilliant illumination and magnification. A preoperative
coronal CT scan is reviewed with particular attention to the position of the fovea
ethmoidalis, skull base, cribriform plate, and the lamina papyracea.
The delicate bone at the junction of the posterior orbital floor and the medial antral wall
is gently perforated with a Wilhelminski punch, and this entrance into the ethmoidal
sinuses is carefully enlarged with a fine biting forceps. The lamina papyracea is an
important landmark and must be identified at this stage. The anterior ethmoidal cells are
dissected in a retrograde manner with a sphenoid punch or a Kerrison rongeur. If
possible, the fovea ethmoidalis is identified anteriorly, and the dissection with forceps
proceeds posteriorly to the face of the sphenoid, the surgeon using the lamina papyracea
and the fovea as guides. In many instances, the fovea is more readily identified
posteriorly, and exenteration of the superior-most ethmoidal cells can be performed in a
retrograde direction. It is worthwhile to remember that the plane of the skull base projects
inferiorly from anterior to posterior. The agger nasi cells are generally not accessible with
this approach, and therefore they are dissected through the nose as described earlier. The
middle turbinate is preserved. Placement of a nasoantral window, nasal packing, and
wound closure proceed as described for the Caldwell-Luc operation. The procedure
concludes with assessment of the consistency of the globes and the diameter of the
pupils. Visual acuity and extraocular movements are evaluated in the recovery room.
Postoperative care and complications (Table 31.4) are similar to those of the procedures
described earlier.

HIGHLIGHTS
The symptoms of inflammatory sinus disease, including nasal
airway obstruction, mucopurulent rhinorrhea, postnasal
drainage, and facial discomfort, diminish a patient's sense of
well-being.
If appropriate medical therapy fails to resolve symptoms,
surgical intervention is indicated.
An understanding of the pathogenesis of sinus disease is
critical. Identification of preexisting mucosal disorders,
assessment of structural abnormalities, and recognition of the
intimate relations between the nasal septum, the turbinates, and
the paranasal sinuses are necessary.
Successful surgical planning requires synthesis of the results of
nasal endoscopy, coronal CT, and allergy evaluation. The
utilitarian procedures described can be used alone or in
combination to address a wide variety of disorders of the
paranasal sinuses.
We urge attention to the status of the ethmoidal sinuses in all
cases of recurrent acute and chronic suppurative sinusitis
because failure to address silent ethmoidal disease is a common
cause of persistent or recurrent disease.
Meticulous hemostasis, atraumatic handling of tissue, brilliant
headlight or microscopic illumination, and the use of two-
power loupes or a microscope for magnification are
emphasized.
Excellent wound healing results from continuing postoperative
care. We recommend frequent nasal irrigation and regular
follow-up visits for cavity cleaning.
Careful patient selection and strict attention to detail in
preoperative evaluation and during the operation produce
excellent results.
CHAPTER REFERENCES
1. Macbeth R. Caldwell, Luc, and their operation. Laryngoscope 1971;81:1652.
2. Macbeth R. Caldwell-Luc operation, 19521966. Arch Otolaryngol 1968;87:630.
3. Messerklinger W. Endoscopy of the nose. Baltimore: Urban & Schwarzenberg, 1978.
4. Messerklinger W. Uber die drainage der menschlinchen nasennebenhohlen unter normalen und
pathologischen bendingungen, II: mitteilungdie stirnhohle und ihr ausfuhrungssystem.
Monatsschr Ohrenheilk Laryngorhinol 1967;101:313326.
5. Messerklinger W. Uber den recessus frontalis und seine klinik. Laryngol Rhinol Otol (Stuttg)
1982;61:217.
6. Messerklinger W. Endoskopische diagnose und chirurgie der rezidivierenden sinusitis. In: Krajina
Z, ed. Advances in nose and sinus surgery. Zagreb, Yugoslavia: Zagreb University, 1985:31.
7. Kennedy DW, Zinreich SJ, Rosenbaum AE, et al. Functional endoscopic sinus surgery: theory and
diagnostic evaluation. Arch Otolaryngol 1985;111:576.
8. Kennedy DW. Functional endoscopic sinus surgery: technique. Arch Otolaryngol 1985;111:643.
9. Poore TE, Carney FMT. Maxillary nerve block: a useful technique. J Oral Surg 1973;31:749.
10. McDonald TJ, Pearson BW. Follow-up on maxillary artery ligation for epistaxis. Arch
Otolaryngol 1980;106:635.
11. Myers EN. Caldwell-Luc operations and extensions. In: Goldman JL, ed. The principles and
practice of rhinology. New York: John Wiley and Sons, 1987:455.
12. Noyek AM, Zinzmor J. Radiology of the maxillary sinus after Caldwell-Luc surgery. Otolaryngol
Clin North Am 1976;9:155.
13. Cable HR, Jeans WD, Cullen RJ, et al. Computerized tomography of the Caldwell-Luc cavity. J
Laryngol Otol 1981;95:775.
14. Yankauer S. Demonstration of intranasal surgery on wet specimens. Laryngoscope 1930;40:642.
15. Mosher HP. The surgical anatomy of the ethmoidal labyrinth. Ann Otol Rhinol Laryngol
1929;38:869.
16. Van Alyea DE. Ethmoidal labyrinth: anatomic study with consideration of the clinical significance
of its structural characteristics. Arch Otolaryngol 1939;29:881.
17. Freidman WH, Katsantonis GA, Slavin RG, et al. Sphenoethmoidectomy: its role in the asthmatic
patient. Otolaryngol Head Neck Surg 1982;90:171.
18. Lawson W. The intranasal ethmoidectomy: an experience with 1077 procedures. Laryngoscope
1991;101:367.
19. Freedman HM, Kern EB. Complications of intranasal ethmoidectomy: a review of 1000
consecutive operations. Laryngoscope 1979;89:421.
20. Maniglia AJ. Fatal and major complications secondary to nasal and sinus surgery. Laryngoscope
1989;99:276.
21. Harrison DF. Surgery in allergic sinusitis. Otolaryngol Clin North Am 1971;4:79.
22. Howarth WG. Operations on the frontal sinus. J Laryngol 1921;36:417.
23. Mattox DE, Delaney RG. Anatomy of the ethmoid sinus. Otolaryngol Clin North Am 1985;18:3.
24. Neel HB, Whiticker JA, Lake CF. Thin rubber sheeting in frontal sinus surgery: animal and
clinical studies. Laryngoscope 1976;86:524.
25. Jansen A. Zur eriffung der nebenhohlen der nase bei chronischer eiterung. Arch Laryngol Rhinol
1894;1:135.
26. Horgan JB. Surgical approach to the ethmoidal cell system. J Laryngol Otol 1926;41:510.
27. Langenbrunner DJ, Nigri P. Transantral ethmoidectomy: an overlooked procedure? Trans Am
Acad Ophthalmol Otolaryngol 1977;4:744.
28. DeSanto LW. Surgical palliation of ophthalmology of Graves' disease: transantral approach. Mayo
Clin Proc 1972;47:989.
29. DeSanto LW, Gorman CA. Selection of patients and choice of operation for orbital decompression
in Graves' ophthalmopathy. Laryngoscope 1973;83:945.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

32 ENDOSCOPIC SINUS SURGERY
Head & Neck SurgeryOtolaryngology
32




ENDOSCOPIC SINUS SURGERY
DONALD C. LANZA
DAVID W. KENNEDY

D.C. Lanza: Department of Otolaryngology, The Cleveland Clinic Foundation, Cleveland, Ohio.
D.W. Kennedy: Department of Otolaryngology, University of Pennsylvania Medical Center, Philadelphia,
Pennsylvania.


Anatomy of the Lateral Nasal Wall
Pathophysiologic Concepts of Rhinosinusitis and the Ostiomeatal Unit
Preoperative Evaluation
Comprehensive Nasal Endoscopy
Radiographic Evaluation
Surgical Indications and Contraindications
Sinonasal Disease among Pediatric Patients
Anesthesia
Local Anesthesia with Sedation
General Anesthesia
Surgical Procedures
Complete Sphenoethmoidectomy
Concurrent Septoplasty
Functional Endoscopic Sinus Surgery
Maxillary or Sphenoidal Sinoscopy
Management of Cerebrospinal Fluid Leak
Orbital Decompression for Dysthyroid Orbitopathy
Endoscopic Intranasal Dacryocystorhinostomy
Endoscopic Marsupialization of Mucoceles
Lasers
Results
Chapter References
The concept of nasal endoscopy has existed for almost a century, but endoscopy was not
used as a surgical approach to the paranasal sinuses until the late 1970s (1,2). Since its
introduction into the United States by Kennedy in 1984, there has been an exponential
increase in the number of sinus procedures performed endoscopically.
Endoscopy is no longer limited to the diagnosis and management of inflammatory
disorders of the nose and paranasal sinuses. It also includes transnasal decompression of
dysthyroid orbitopathy (3), repair of cerebrospinal fluid (CSF) rhinorrhea (4), intranasal
dacryocystorhinostomy, repair of choanal atresia, and management of small anterior and
middle cranial fossa skull-base lesions. Endoscopic management of malignant tumors has
been used as part of a minimally invasive approach (5). As the technology continues to
evolve, endoscopic transsphenoidal hypophysectomy (6) and optic nerve decompression
for traumatic optic neuropathy are being performed. Despite the technologic advances,
ethmoidectomy performed endoscopically still carries all the risks of intranasal
ethmoidectomy. Extensive experience with the instrumentation and an intimate
knowledge of the lateral nasal wall are needed for safe surgery. Diagnosis of nasal and
paranasal disease is, however, the most important aspect of nasal endoscopy, not its direct
application to surgery.
ANATOMY OF THE LATERAL NASAL WALL
Although the anatomic features of the lateral nasal wall have been known for some time,
terms used to define sinonasal anatomic landmarks have been used loosely, so there are
discrepancies in the literature. A proposal has been made to standardize the nomenclature
used to describe sinonasal anatomic features (7), and these terms are used herein.
The ostiomeatal unit is the main functional and anatomic region within the anterior
middle meatus. However, there is no consensus to define the exact borders and margins
of this anatomic region. It is probably best considered a functional unit more than an
anatomic unit. Because of its location and narrow passageways, the ostiomeatal unit is
frequently related to the final common pathway for anterior ethmoidal, frontal, and
maxillary rhinosinusitis. The anterior middle meatus reaches its apex where the
superoanterior margin of the middle turbinate abuts the lateral nasal wall. The lateral
nasal wall is represented by the ascending (frontal) process of the maxilla. Inside the
nose, this thick bony ridge is known as the agger nasi and is just proximal to the
membranous attachment of the uncinate process. Pneumatization of the agger nasi occurs
frequently, but the term agger nasi cell often is applied to any cells anterior to the
opening of the frontal sinus (8).
The ostiomeatal unit is bordered medially by the anterior middle turbinate and laterally
by the lateral nasal. The crescent-shaped uncinate process bisects this region in an
anteroposterior direction. In the anterior aspect, the uncinate process is joined to the
posteromedial portion of the lacrimal bone by a membranous attachment. Occasionally it
attaches anterosuperiorly to the lamina papyracea, or it attaches to the skull base.
Inferiorly and laterally, the uncinate process fuses with the medial wall of the maxillary
sinus to attach to the perpendicular process of the palatine bone and more anteriorly and
medially with the superior surface of the inferior turbinate. Lateral to the uncinate process
is the trough-like ethmoidal infundibulum. The lateral wall of the infundibulum is the
medial wall of the orbit and antrum. In the posterior aspect the ethmoidal infundibulum
empties into the inferior hiatus semilunaris. The ethmoidal bulla forms one of the most
constant of ethmoidal air cells and constitutes the posterior boundary of the inferior
hiatus semilunaris.
The bony medial wall of the maxillary sinus typically has several dehiscences. The most
notable are the natural ostium of the maxillary sinus and the anterior and posterior
fontanelles. The natural ostium, shaped like an inverted funnel, empties into the inferior
aspect of the ethmoidal infundibulum. After removal of the uncinate process, the ostium
usually can be found approximately at a level opposite the inferior free margin of the
middle turbinate.
The fontanelles are bony dehiscences inferior (anterior fontanelle) or superior (posterior
fontanelle) to the inferior limb of uncinate process (Fig. 32.1). The fontanelles usually are
covered by mucosa, but in 10% to 28% of patients, they are perforated, and the
perforation produces an accessory ostium to the maxillary sinus (1,9). We believe that
these accessory ostia are like tympanic membrane perforations and probably represent
previous ostiomeatal obstruction.

FIGURE 32.1. Parasagittal view of the bony lateral nasal
wall shows the lateral attachment of the ground lamella to
the lateral nasal wall and the relation of the uncinate
process to the inferior and posterior fontanelles. The
sequence of five bony landmarks traversed during
complete sphenoethmoidectomy on a patient who has not
undergone other sinus surgery is uncinate, ethmoidal
bulla, basal lamella middle turbinate, superior turbinate,
anterior sphenoidal sinus. 1, Edge of superior turbinate (resected); 2, edge of middle
turbinate (resected); 3, edge of inferior turbinate (resected); 4, ethmoidal bulla; 5,
uncinate process; 6, hiatus semilunaris; 7, agger nasi; 8, inferior turbinate bone; 9,
lacrimal bone; 10, frontal process of maxilla; 11, posterior nasal fontanelle; 12,
sphenopalatine foramen; 13, anterior nasal fontanelle.



The frontal sinus empties through the frontal sinus ostium into the frontal recess. The
frontal recess typically drains medially to the uncinate process and laterally to the middle
turbinate into the anterior superior limit of the middle meatus. Occasionally it drains into
the inferior hiatus semilunaris. The medial boundary of the recess is formed by the
middle turbinate. In some instances, the posterior boundary is formed superiorly by the
base of the skull, and the frontal recess is bound anteriorly by the agger nasi, which is
typically pneumatized.
The sinus lateralis is now called the retrobullar recess and is the most posterior aspect of
the anterior ethmoidal cells. A suprabullar recess, which is the area above the ethmoidal
bulla, may extend into a retrobullar recess if the posterior wall of the bulla lamellae is not
in contact with the lamella of the middle turbinate. The bulla lamellae is that lamella of
bone that when pneumatized forms the ethmoidal bulla. If present, the retrobullar recess
lies directly behind the ethmoidal bulla and drains into the superior hiatus semilunaris
(posterioris). Viewed in the sagittal plane, the basal lamella is the lateral, sigmoid, bony
attachment of the middle turbinate to the medial orbital wall (Fig. 32.1). It separates the
anterior and posterior ethmoidal air cells.
Three different configurations of the ethmoidal roof were described by Keros (7).
Differentiation of the type depends on the length of the lateral lamella of the cribriform
plate. The depth of the olfactory fossa in a Keros type 1 cribriform plate is 1 to 3 mm.
Keros type 2 olfactory clefts are 4 to 7 mm deep, while Keros type 3 is 8 to 16 mm deep
(7). The posterior ethmoidal labyrinth terminates adjacent to the sphenoid bone.
Approximately 12% of sphenoid bones are pneumatized by an ethmoidal air cell
previously known as an Onodi cell but now called a sphenoethmoidal cell (Fig. 32.2) (8).
The apex of this pyramidal sinus is directed posteriorly and laterally and may pneumatize
in a position posterior to the anterior face of the sphenoid sinus. The optic nerve runs
along the lateral wall of this cell and crosses its apex medially to continue its course
along the lateral wall of the sphenoidal sinus. Depending on its size, the sphenoethmoidal
cell can pneumatize for a variable extent around the optic nerve. In extreme cases, the
nerve may appear to cross through the center of this sinus, making it essential that the
surgeon be familiar with the anatomic variations of this area. Direct trauma to the optic
nerve, although rare, is more likely to occur in this area than in the sphenoidal sinus. The
sphenoidal sinus is inferior and medial to the region of the most posterior ethmoidal cell.
Its natural opening is medial to the superior turbinate. The vertical location of this natural
ostium in the sphenoethmoidal recess usually is within millimeters of the inferior border
of the superior turbinate. The sphenoidal sinus is partitioned by a septum of bone. Not
infrequently, the bony septum of the sphenoidal sinus attaches to the lateral wall of the
sinus adjacent to the optic nerve and carotid artery. In that case, manipulation of the bony
septation can be disastrous and disrupt these vital structures. Clinical bony dehiscence of
the cavernous portion of the carotid canal occurs among 22% of patients (10).

FIGURE 32.2. Sequential coronal computed
tomographic images from anterior to posterior show the
appearance and relation of a sphenoethmoidal cell (*),
sphenoidal sinus (S), and optic nerve (ON).



PATHOPHYSIOLOGIC CONCEPTS OF RHINOSINUSITIS AND THE
OSTIOMEATAL UNIT
The predisposing factors for rhinosinusitis are incompletely elucidated. Definitions of the
terms used for acute, subacute, chronic, recurrent acute, and acute exacerbation of
chronic rhinosinusitis were detailed in a statement produced by the Rhinosinusitis Task
Force and is endorsed by the American Academy of OtolaryngologyHead and Neck
Surgery (11). Chronic rhinosinusitis is becoming considered a medical problem in which
surgery may play a role. Congenital or acquired immunodeficiency syndrome, ciliary
dyskinesia, cystic fibrosis, and Young syndrome are predisposing factors. Most clinicians
believe allergy is an important predisposing factor, but the precise relation between
allergy and sinusitis is unclear. Some data suggest that viral respiratory infection is
important in the development of chronic rhinosinusitis. The influences of environmental
pollution, heredity, and stress on the pathogenesis of rhinosinusitis require further study.
The association between rhinosinusitis and asthma and the overall concept of hyperactive
airways disease remain poorly understood. Whatever the predisposing causes of
rhinosinusitis in a particular patient, it appears that the ostiomeatal complex is integral as
a flow-limiting segment. However, it appears as though the role of the ostiomeatal
complex has been overemphasized as a sole underlying cause of the development of
chronic rhinosinusitis.
Current understanding of the pathophysiologic features of the ostiomeatal unit has
developed from several independent observations. Mucociliary clearance within the
maxillary and frontal sinuses has specific patterns of drainage toward the natural ostium
(Fig. 32.3). There is also some recirculation of mucus into the frontal sinus from the
frontal recess (12). These mucociliary clearance patterns make the sinuses functionally
dependent on the ostiomeatal complex, even if there is an accessory ostium or window
into the sinus. Inhalation of aerosolized pollen-sized droplets of radiolabeled water shows
the greatest accumulation in the anterior portion of the nose, on or adjacent to the middle
turbinate (13). It is not surprising that computed tomographic (CT) studies show that
mucosal thickening occurs most frequently in the ostiomeatal complex. Among workers
occupationally predisposed to nasal neoplasia, the lateral nasal wall adjacent to the
middle turbinate is the common site of neoplasia, such as squamous carcinoma among
nickel workers and adenocarcinoma among wood workers.

FIGURE 32.3. Mucociliary clearance patterns in the
maxillary and frontal sinuses.



Theoretic evidence and clinical evidence suggest that the ostiomeatal complex typically
is the first site to be involved in inflammatory rhinosinusitis. Chronic mucosal
inflammation and hypertrophy in this area can lead to inflammation and mucociliary or
ventilatory obstruction of the anterior ethmoidal, maxillary, or frontal sinuses. After
treatment, low-grade inflammation and mucosal hypertrophy may remain in the
ostiomeatal complex and cause recurrent infection. Anatomic variations that narrow or
obstruct the anterior ethmoidal region may be important in predisposing some patients to
chronic sinus disease, but they are not in and of themselves an indication for surgery.
PREOPERATIVE EVALUATION
Comprehensive Nasal Endoscopy
Nasal endoscopy has greatly improved the ability to diagnose disease and assess the
response to medical and surgical therapy. Because anterior rhinoscopy is inadequate,
endoscopy is performed as part of the complete evaluation of any patient with chronic
symptoms that can be referred to the nose or paranasal sinus. Isolated maxillary disease
may be dental in origin; therefore dentition is evaluated as part of a complete
otolaryngologic examination.
Anterior rhinoscopy is used to initiate the nasal examination and to administer topical
vasoconstrictors and anesthetic sprays. Patients who have adequate nasal airflow are
asked to hold their breath while being sprayed. Sniffing in the anesthetic during spraying
promotes aggressive anesthesia of the larynx that can cause the patient the sensation that
the throat is closing in or a sensation of inability to breathe or swallow. An anxious
patient does not tolerate nasal endoscopy well. To avoid problems, the patient is asked to
lean forward and sniff in gently so that the anesthetic does not drip from the nose. This
method typically brings about more intense nasal anesthesia and may be associated with
temporary numbness of the upper incisor region. Cotton-tipped applicators soaked in 4%
cocaine solution are introduced atraumatically under endoscopic guidance into the nose
when necessary. Applicators are placed intranasally on each side along regions where
pressure is likely to be exerted.
A comprehensive nasal endoscopic examination of an adult is initially performed with
either a flexible fiberoptic endoscope or a 30-degree 4-mm telescope after topical nasal
decongestants and anesthetics have taken effect. The procedure consists of three passes,
during which the overall condition of the nasal mucosa (Table 32.1) and pathologic
secretions are observed. Endoscopically obtained cultures should not be confused with
nasal swabs. New data confirm that results of endoscopically obtained culture of the
middle meatus correlate with antral puncture data in acute maxillary rhinosinusitis (14).

TABLE 32.1. EVIDENCE OF SOFT-TISSUE
DISEASE FOUND AT ENDOSCOPY



The first pass along the floor of the nose allows visualization of the inferior turbinate,
inferior meatus, nasopharynx, and eustachian tube orifices. Occasionally the opening of
the nasolacrimal duct (Hasner valve) can be seen superiorly within the anterior third of
the inferior meatus. This may not be a routine aspect of the examination, however.
Identification of the opening is simplified when tears can be expressed by means of
simultaneous palpation of the ipsilateral lacrimal sac. Mucopus draining from the opening
can signify inflammation of a pneumatized agger nasi. Similar drainage under the torus
tubarius suggests disease within the anterior ethmoidal, maxillary, or frontal sinuses.
Purulence passing above the eustachian tube opening usually emanates from the
sphenoethmoidal recess and signifies posterior ethmoidal or sphenoidal sinus disease.
The endoscope is reintroduced between the middle turbinate and the inferior turbinate.
The anterior and inferior portions of the middle turbinate and meatus are inspected during
the pass to the sphenoethmoidal recess, and the natural opening to the sphenoidal sinus is
viewed. The third pass is performed during withdrawal of the telescope. The telescope is
rolled superiorly and laterally up into the anterior middle meatus. Here the ethmoidal
bulla, inferior hiatus semilunaris, and uncinate process can be visualized. Any accessory
ostia also are examined. The natural ostium of the maxillary sinus remains hidden from
view, because its position is typically lateral to the uncinate process and is rarely seen
during routine comprehensive nasal endoscopy.
The middle turbinate sometimes can be gently moved medially by means of subluxation
to gain access to this region. An alternative is to substitute a 2.7-mm telescope to inspect
a constricted middle meatus. Slight medial displacement of the middle turbinate with a
nasal applicator impregnated with a 4% solution of cocaine also allows entry without
causing trauma to the mucosa. Patients should be warned before the examination that
they may hear a bone-cracking noise or that slight bleeding may occur. Coronal CT
complements the findings of the physical examination.
Radiographic Evaluation
Computed tomography can be helpful if the symptoms strongly suggest sinus disease yet
nasal endoscopy provides minimal or unremarkable findings. Computed tomography is
indispensable in planning endoscopic sinus surgery. Scanning is best performed in the
coronal plane, but axial images through the sphenoidal sinus can be helpful in delineating
depth, pneumatization, and the relation of sphenoidal septations to the cavernous portion
of the carotid artery and optic nerve.
There is occasionally considerable disparity between the extent of disease revealed at
surgery and that seen at CT. The extent of mucosal disease found during surgery usually
is greater than that seen at CT. Although CT is less sensitive in assessing the extent of
mucosal disease, the disparity also depends on the interval between endoscopy and CT.
The optimal time to perform CT is during a quiescent phase of the disease. This
diminishes the effect of acute inflammation and allows identification of specific anatomic
areas of narrowing or disease. Patients should therefore undergo comprehensive medical
therapy before they undergo CT.
Computed tomography of the paranasal sinuses can depict anatomic variations not
routinely seen at preoperative nasal endoscopy. Fungal disease should be suspected if
plain radiographs or CT scans of the paranasal sinuses show metal-like or diffusely
increased densities within the soft tissues of the involved sinuses. The reduced signal
intensity of a T2-weighted magnetic resonance image can suggest fungal sinus disease
(15). Extramucosal fungal rhinosinusitis seems to be more prevalent than had been
previously recognized. To avoid complications, the surgeon should routinely review
images before surgery and make a checklist of the important features to be examined
(Table 32.2; Fig. 32.4 and Fig. 32.5).

TABLE 32.2. PREOPERATIVE RADIOGRAPHIC
CHECKLIST



FIGURE 32.4. Coronal computed tomographic scan near
the level of the natural ostium of the maxillary sinus
shows sharply sloped base of the skull leading into the
supraorbital ethmoidal cells and the prominent left
concha bullosa (+).



FIGURE 32.5. Coronal computed tomographic scan
through the level of the posterior ethmoidal air cells.
Soft-tissue hyperdensities are evident in the left maxillary
sinus (+) of this patient with Bipolaris spicifera allergic
fungal rhinosinusitis. Widening of the ethmoid complex
is present.



SURGICAL INDICATIONS AND CONTRAINDICATIONS
The advantages of an endoscopic approach to chronic sinus disease are compared with
those of traditional surgery on the paranasal sinuses in Table 32.3. Relative indications
for and contraindications to surgical endoscopy are listed in Table 32.4 and Table 32.5.
Endoscopic sinus surgery for inflammatory disease of the paranasal sinuses is indicated
for patients who have documented disease and have not responded to a trial of medical
therapy (Table 32.6). Endoscopy usually is not recommended for acute inflammatory
disease, but it may be appropriate in some instances if the surgeon is highly experienced.
Some centers advocate this technique as an alternative approach to external drainage for
acute unresponsive sinus disease and in the management of periorbital abscess (16).

TABLE 32.3. ADVANTAGES OF ENDOSCOPIC
APPROACH TO CHRONIC RHINOSINUSITIS



TABLE 32.4. RELATIVE INDICATIONS FOR
ENDOSCOPIC SURGERY



TABLE 32.5. RELATIVE CONTRAINDICATIONS
TO ENDOSCOPIC SURGERY



TABLE 32.6. TREATMENT REGIMENS



SINONASAL DISEASE AMONG PEDIATRIC PATIENTS
Endoscopic diagnosis of sinonasal disease, surgical management, and postoperative care
often are more challenging for children than they are for adults. However, most children
with rhinosinusitis improve over time with medical management, and the need for
surgical intervention is the exception rather than the rule (17). Some otolaryngologists
maintain that management of allergic rhinitis, gastroesophageal reflux, and other
conditions that can be managed medically can relieve most cases of pediatric
rhinosinusitis (18).
Children 6 years of age and younger rarely tolerate telescopic evaluation without general
anesthesia. In-office postoperative dbridement is equally intolerable, and a return visit to
the operating room often is necessary. Chronic nasal discharge in a pediatric patient
indicates the possibility of adenoidal obstruction or sinus disease. It is advisable to
consider managing chronic maxillary sinus disease refractory to medical therapy with an
initial trial of inferior meatal antrostomy. This option should be considered because of the
difficulties in postoperative dbridement of pediatric ethmoidal cavities and the risk of
subsequent middle meatal or frontal recess scarring and persistent sinus disease. Children
with cystic fibrosis may have vitamin K deficiency and coagulopathy. The
instrumentation used in pediatric endoscopic sinus surgery is tailored for this population,
but most of the procedures are performed with 4-mm telescopes.
ANESTHESIA
Regardless of the anesthetic technique chosen, atraumatic, intranasal local injection of a
solution containing a vasoconstrictor is required. There is diversity of opinion among
otolaryngologists about the safest way to administer anesthesia during endoscopic sinus
surgery. Some maintain that the risk of complications under general anesthesia is greater
than during surgery performed under local anesthesia with sedation. The surgical risk to
the patient increases as the surgeon's ability to visualize the field diminishes. Therefore
the greater surgical risk associated with general anesthesia is linked to risk of greater
blood loss than with local anesthesia (19).
Intraoperative physician-patient communication may reduce the risk of complications.
The medial orbital wall and orbital periosteum are sensitive to pain, and the skull base is
pain sensitive in the area where it usually is thinnestthe area of the anterior ethmoidal
nerve. If an ethmoidal vessel is injured and retracts into the orbit, a hematoma may form.
Vision can be carefully monitored if the patient is awake, and corrective measures can be
undertaken rapidly. However, although local anesthesia has definite advantages, we are
performing an increasing percentage of procedures with general anesthesia. Because the
importance of combining mucosal preservation with careful removal of bone is being
recognized, our surgical procedures have tended to become longer and more meticulous,
making local anesthesia a limited alternative. Although we do not use a suction irrigation
device, endoscopic techniques with a suction irrigator mandate general endotracheal
anesthesia. When local anesthesia is used, it is important that both the surgeon and the
anesthesiologist be highly experienced with the techniques.
Local Anesthesia with Sedation
After the patient is adequately sedated with a narcotic and a benzodiazepine, usually
midazolam, vasoconstriction and topical anesthesia are achieved. Oxymetazoline used
before application of cocaine has been shown to slow absorption of the latter agent and
diminish its cardiovascular effect (20). An alternative is to administer 0.05%
xylometazoline and 2% tetracaine or 4% cocaine alone. Topical anesthesia is directed at
the branches of the ethmoidal and sphenopalatine vessels and nerves.
A sphenopalatine block can be helpful in controlling bleeding and in anesthesia. When
the block is administered transorally through the greater palatine foramen, care must be
used not to advance the needle tip more than 2.5 cm into the foramen. This reduces the
risk of trauma to the contents of the posterior orbit and of blindness. The sphenopalatine
neurovascular bundle can be accessed transnasally when the posterior route of the middle
turbinate can be seen. An angled tonsil needle is passed through the inferior basal lamella
of the middle turbinate into the foramen. Although helpful in controlling bleeding, neither
route of injection of the sphenopalatine region is completely safe. We have seen
temporary diplopia, and visual loss has been reported by others.
Other intranasal injections are performed with a 2-inch (5 cm) 25-gauge needle. Under
direct vision with a 4-mm 0-degree telescope, the lateral nasal wall is injected with a
solution of 1% lidocaine with 1:100,000 epinephrine. The number of injection sites is
kept to a minimum and away from the regions where the endoscope is to pass (Fig. 32.6).
This minimizes bloody contamination of the distal endoscope. The typical injection sites
are the ascending process of the maxilla (agger nasi), medial surface of the middle
turbinate, and portions of the nasal septum. Injections are administered into one side of
the nose at a time so that anesthetic and vasoconstrictive properties do not wear off
during the procedure. After the anesthetic has had sufficient time to take effect (usually
about 10 minutes), the surgical procedure begins. The patient is instructed to breathe
through the mouth during the procedure to avoid droplets of blood on the telescope lens.
It is helpful periodically to place a small, temporary sponge (polyvinyl acetal choanal
pack) in the posterior choana.

FIGURE 32.6. Endoscopic view of the nose shows a
minimum number of sites for injection of local anesthesia
(circles).



This anesthetic technique sometimes is insufficient. External injections can be used to
augment anesthesia, or conversion to general anesthesia may be necessary. In cases of
severe polyposis, initial intranasal injection beyond the anterior lateral nasal wall may be
impossible. External transorbital injection of the anterior and posterior ethmoidal
neurovascular bundles can be used. However, this injection usually is associated with
orbital ecchymosis and can produce orbital hematoma. An infraorbital nerve block can be
used for anesthesia during a sublabial approach to maxillary sinoscopy.
Repeated injections of anesthetic may be needed, particularly if there is massive
polyposis. Toxic doses of anesthetic are avoided if the amounts injected are recorded. In
the unique instance of a patient with both massive polyposis and septal perforation,
unilateral nasal injection is inadequate because hemorrhage from contralateral polyps
pours through the perforation. Powered instruments such as microarthroscopic dbriders
(soft-tissue shavers) have been used, as have lasers (potassium titanyl phosphate 532
laser) to help debulk polyps. Soft-tissue shavers seem to be an important enhancement in
endonasal surgery, particularly for patients with polyps. When this tool is used to sculpt
the underlying bony anatomic structures, landmarks can be better defined. Surrounding
tissues can be clearly elucidated, and the safety of the procedure is enhanced.
General Anesthesia
Proponents of general anesthesia believe that patient comfort is superior and anxiety
decreased with this approach. The use of general anesthesia usually mandates placement
of ethmoidal packs at the end of the operation if postoperative bleeding is to be avoided.
Low-normal blood pressure is maintained throughout the procedure. Controlled
hypotension, however, carries high risk for geriatric and pregnant patients and usually is
avoided in operations on these patients. The use of halothane in conjunction with
vasoconstrictors is discouraged because of the risk of cardiac irritability. Throat packing
or the use of an orogastric tube decreases the probability of nausea and emesis caused by
blood in the stomach. These maneuvers do not prevent nausea and vomiting, which are
common reactions to general anesthesia.
SURGICAL PROCEDURES
Complete Sphenoethmoidectomy
Two classic endoscopic approaches (Messerklinger and Wigand) are used for complete
sphenoethmoidectomy with frontal sinusotomy and middle meatal antrostomy. Because
the Messerklinger approach is most widely used in the United States, our adap-tation of
this technique is detailed herein. Similar results can be achieved with either classic
method, and both approaches are recommended only for surgeons who have specific
training in endoscopic techniques. Endoscopic sphenoethmoidectomy is indicated for
extensive sinus disease. Disease limited to the ostiomeatal complex does not necessitate
this complete procedure. Information gathered preoperatively by means of the endoscopic
approach in conjunction with CT enables the surgeon to tailor the procedure to each
patient. An integral strategy for all successful operations on the sinuses is safe
identification of the medial orbital wall and base of the skull. The anterior aspect of the
base of the skull is most difficult to identify in the position just posterior to the frontal
recess. It is also thinnest in this region. It usually is safest to first identify the posterior
aspect of the base of the skull and follow it forward to this region.
In a case of massive nasal polyposis, staging the operation is a viable and safe approach.
Even experienced surgeons may leave small areas of disease during surgery. These can
be removed in postoperative care, when in the absence of bleeding the landmarks can be
more easily identified. Regardless of the endoscopic approach, surgery should always be
terminated whenever adequate visualization is lost.
Concurrent Septoplasty
Septoplasty should be begun in a standard manner after the endoscopic procedure is
completed on the side away from the septal deflection (21). For diffuse septal deformities
or a caudal deformity, a hemitransfixion incision is made on the side contralateral to the
deflection. All flaps are elevated through this incision to minimize trauma and bleeding
on the side that still requires endoscopic surgery. The septum is mobilized in the region
of narrowing, and the sinus surgery is undertaken on the side ipsilateral to the deflection.
The deviated bone and cartilage are resected under direct endoscopic visualization with
scissors or through cutting punches. A mattress suture is made with 4-0 plain catgut. We
perform approximately 85% of septoplasties in this manner. After sinus surgery is
completed, reconstruction of the septum is performed, and septal splints are placed.
For more limited deformities, we use an endoscopic approach and make a modified
Killian incision anterior to the area of deflection on the side of the nose on which the
operation is being performed. The mucosal flap is elevated with a suction elevator. A
cartilaginous incision is made 3 to 5 mm posterior to the mucosal incision, and the flap
on the opposite side is raised over the deviation. Isolated septal spurs can be removed
endoscopically with minimal morbidity.
Functional Endoscopic Sinus Surgery
Functional endoscopic sinus surgery is a philosophy as much as a surgical technique. The
philosophy is that with removal of disease from a target area such as the ostiomeatal
complex, normal mucociliary flow is restored and disease in dependent sinuses resolves.
Therefore it may not be necessary to perform complete exenteration of the mucosa of the
ethmoid, maxillary, sphenoidal, or frontal sinuses after the obstructing sites are relieved.
According to this philosophy, it is not necessary to perform complete
sphenoethmoidectomy if there is limited ethmoidal disease. However, it does not mean
that less than meticulous, complete sphenoethmoidectomy should be performed when
there is diffuse disease. Through-cutting instrumentation and microdbriders (soft-tissue
shavers) have been a technical advance toward a mucosa-sparing procedure.
Advancement in soft-tissue shaver technology allows use of powered instruments in most
complete sphenoethmoidectomy and middle meatal antrostomy procedures.
As in the Messerklinger approach, a technique called transition space surgery or small
hole surgery has been recommended for superior control of disease that involves the
ostiomeatal complex. As in the philosophy espoused for functional endoscopic sinus
surgery, one of the essential points in this approach is that disease of secondarily
involved sinuses resolves once the obstructed area is adequately ventilated. In certain
situations, middle meatal antrostomy is not recommended once the uncinate process is
adequately and atraumatically removed with a soft-tissue shaver. Proponents of this
technique argue that this is the most functional operation and yields excellent results in
the management of limited anterior ethmoid and maxillary disease. They suggest that the
operation hastens recovery and limits the use of antibiotics. This may have important
implications, because bacterial resistance to antimicrobial therapy is a national concern.
Opponents argue, however, that appropriate medical therapy, which can include culture-
directed antibiotics and perhaps a brief course of systemic steroid therapy, reverses such
limited disease. The opponents argue further that the costs of such limited surgery
compared with that of well-tolerated medical therapy do not justify small hole surgery
until more appropriate medical therapy has been used. There are further concerns that this
limited approach is insufficient for chronic rhinosinusitis.
Although an endoscopic approach can be used in the care of patients with immotile cilia
syndrome, a functional approach is not indicated because there is no hope for return of
normal mucociliary clearance. These patients need gravity-dependent inferior
antrostomy. In this regard, patients with cystic fibrosis are candidates for large middle
meatal antrostomy that extends from the natural ostium to the floor of the nose.
The entire Messerklinger sphenoethmoidectomy is performed endoscopically. As the
angle of the telescope increases, so does the risk of disorientation. A 0-degree telescope is
used for most of the procedure. Thirty-degree and 70-degree endoscopes are used only
when necessary for work in angled recesses after the important landmarks have been
identified. The two most critical boundaries of endoscopic dissectionthe medial orbital
wall and the base of the skullare also the most constant landmarks in dissection. In
operations on patients who have not undergone previous surgery, four bony landmarks
can be followed while the medial orbital wall is skeletonized in an anteroposterior
direction (Fig. 32.1). They are the uncinate process, ethmoidal bulla, basal lamella of the
middle turbinate, roof of the maxillary sinus, superior turbinate, and anterior face of the
sphenoidal sinus.
Most important in the operation is to avoid trauma to the mucosa of the anterior portion
of the nose. Even minimal bleeding from this area can contaminate the lens of the
endoscope and impair visualization. It is also important not to bring the tip of the
endoscope too close to the area of surgery during dissection (Fig. 32.7). This can
contaminate the lens and cause disorientation. From time to time during dissection, the
telescope should be partially withdrawn to confirm the correct orientation. Routine
resection of the middle turbinate as part of this surgical procedure is not part of the
Messerklinger technique and is not necessary. The goal of the procedure is to avoid any
unnecessary trauma to the middle turbinate and thereby avoid any risk of adhesions. It
has been argued that surgical access is improved with this maneuver. Compelling proof
that the middle turbinate is clearly deleterious as a routine procedure is lacking; however,
it has been suggested that middle turbinate resection is linked to iatrogenic postoperative
frontal sinus disease (22).

FIGURE 32.7. Incision in the lateral nasal wall just
proximal to the uncinate process (infundibulotomy) is
used to expose the ethmoid infundibulum and is followed
by uncinectomy. The hand holding the nasal endoscope is
immobilized by means of gently resting it against the
patient's face during the procedure.



The basal lamella is perforated inferiorly and just at the level of the roof of the maxillary
sinus, which roughly correlates with the level of the free border of the middle turbinate. If
the basal lamella of the middle turbinate is penetrated here, the superior meatus and
superior turbinate often can be identified. These are both useful guides toward safe
sphenoidotomy. The base of the skull is identified in the posterior ethmoidal air cells or
within the sphenoidal sinus. The sphenoidal sinus is always located more inferiorly and
medially than usually is expected by the surgeon. The correct position and depth of the
anterior face of the sphenoid usually can be ascertained by means of identifying the sinus
ostium medial to the superior and middle turbinates. The safest way to enter the
sphenoidal sinus from the ethmoid sinuses is to identify the superior meatus and turbinate
from within the ethmoid cavity. The inferior portion of the superior turbinate is resected
with a through-cutting instrument. No more than the inferior 25% of the superior
turbinate is resected. Avoiding twisting or pulling during this maneuver minimizes the
additional risk of turbinate trauma, olfactory loss, and CSF leak. The natural ostium of
the sphenoidal sinus is identified, and the anterior wall of the sphenoidal is resected with
through-cutting punches.
The base of the skull is followed in a posteroanterior direction. Along the base of the
skull are the posterior and anterior ethmoidal vessels and nerves. The anterior ethmoidal
artery typically is just anterior to the vertical portion of the basal lamella, immediately
below the base of the skull, and posterior to the frontal recess. Sometimes there are two
openings side by side in this vicinity. The more medial and anterior of the two usually are
the frontal recess, and the lateral ostium opens into a supraorbital ethmoidal sinus.
Several cautions apply to sphenoethmoid dissection. It is safer to perform the initial
uncinectomy somewhat more posteriorly than anteriorly. Small remnants of the uncinate
process can be gently removed afterward. This decreases the risk of injury to the thick
mucosa of the lateral nasal wall or even to the nasolacrimal duct.
Although the lamina papyracea can be removed with relative impunity, injury to the
periorbital area should be avoided. However, identification of a small amount of orbital
fat is not an indication for terminating the procedure. As long as no fat has been removed,
the protruding fat should be gently replaced and the area carefully avoided. An alternative
is to apply bipolar cautery with the warning that it should not be used in the region of the
medial rectus muscle. Orbital hematoma can be caused by any manipulation of the orbital
or ethmoidal artery. Tight nasal packing should be avoided when the integrity of the
orbital wall is in question. With nasal packing, blood can dissect into the orbit
postoperatively and cause delayed hematoma and vision loss. After a more severe orbital
penetration, the medial rectus muscle can be damaged, and the resulting diplopia can be
permanent.
Within the sphenoidal sinus, the bony wall of the carotid artery may be dehiscent. Care
should be taken in the removal of intersinus septa in the sphenoidal sinus because these
may attach to the carotid canal. Attached, thickened sphenoidal sinus mucosa should be
left in place or removed with great care. Direct trauma to the optic nerve is probably
more likely to occur in the posterior ethmoidal area. The most posterior ethmoid cell can
pneumatize into the sphenoid bone (sphenoethmoid cell, previously called an Onodi cell)
lateral and superior to the sphenoidal sinus. In this situation, the cell develops an intimate
relation with the optic nerve, and the nerve can markedly indented the lateral wall of the
cell, or the cell can pneumatize widely around the nerve. The most posterior ethmoidal
cell has a typical pyramidal shape, which is useful in recognizing the cell during
endoscopy. The apex of the pyramid points toward the anterior clinoid process, and the
optic nerve is closely related to the lateral wall adjacent to the apex of the cell.
The base of the skull usually is thinnest where the anterior ethmoidal artery crosses from
the medial orbital wall to the cribriform plate. The roof is particularly thin medially
where the ethmoid roof slopes down into the middle turbinate (lateral lamella of the
cribriform plate). It is therefore important to skeletonize and remain close to the medial
orbital wall during dissection. During dissection in the frontal recess, the forceps should
always point laterally. Resistance encountered during extirpation of the ethmoidal cells or
polyps may indicate that an olfactory fiber has been grasped; tearing it can cause leakage
of CSF.
The maxillary sinus can be entered soon after resection of the uncinate process or after
the frontal recess work. Opening the maxillary sinus earlier during the procedure can
have several advantages. The roof of the maxillary sinus is a helpful landmark to gauge
both lateral (orbit) and vertical (base of the skull) position during ethmoidal surgery. It
can also serve as a receptacle for blood. When this procedure is performed earlier,
bleeding from above does not obscure visualization of the natural ostium. Blood usually
pools inferiorly and posteriorly within the sinuses. Thus it is advantageous to perform the
anterior and superior portions of the procedure last. This is particularly true during
revision sinus surgery. The maxillary sinus can be entered in the area of the posterior
fontanelle rather than at the natural ostium. When this mode of entry is used, it must be
performed sharply or through an accessory ostium. Pressure in the posterior fontanelles
with a blunt instrument risks invaginating the mucosa into the sinus. It is also important
that the opening be connected anteriorly to communicate with the ostium. Failure to
connect a surgical antrostomy with a natural ostium appears to be the most common
cause of failure in resolving maxillary sinus disease. However, because the nasolacrimal
duct is immediately anterior to the natural ostium, great care must be taken not to bring
the opening too far anteriorly. Epiphora due to nasolacrimal duct stenosis may not be
apparent for several months. It rarely necessitates dacryocystorhinostomy (23).
Complications of sinus surgery are discussed in Chapter 35. Postoperative endoscopic
dbridement of the cavity and removal of adhesions are essential. Like a mastoid cavity,
ethmoid cavities endoscopically produced are doomed to failure if both patient and
surgeon are not committed to meticulous postoperative care.
Maxillary or Sphenoidal Sinoscopy
Although rarely performed, sinoscopy of the maxillary or sphenoidal sinuses can be
performed with a trocar and cannula. It is not part of a routine examination but can be
useful in the early diagnosis of tumors or fungus balls of the antrum. Entrance into the
maxillary sinus usually is through the canine fossa.
Management of Cerebrospinal Fluid Leak
Until the widespread use of diagnostic nasal endoscopy, the source of CSF rhinorrhea
was almost never identified in the otolaryngologist's office. However, nasal endoscopy is
a useful method of localization. Difficult to locate leaks can be found endoscopically
after intrathecal injection of fluorescein (4). Intranasal endoscopic repair has been
performed with free grafts and pedicled septum-turbinate mucosal flaps. Septal
mucoperiosteal free grafts taken from the opposite side of the nose have nearly a 95%
success rate (4). Postauricular fascia and muscle grafts and turbinate mucosal grafts also
have been successful (19).
Orbital Decompression for Dysthyroid Orbitopathy
Only surgeons with a great deal of experience with endoscopic operations on the sinuses
should perform endoscopic orbital decompression. Results with this technique appear to
be comparable with those with other approaches. Success is in part a result of the
excellent decompression achieved in the area of the orbital apex. With this technique, the
orbital floor cannot be removed laterally to the infraorbital nerve, and some bone is left in
a position medial to the nerve in the anterior portion of the maxillary sinus. Concurrent
lateral orbitopathy is necessary if decompression lateral to the infraorbital nerve is
needed. Endoscopic orbital decompression does not carry the morbidity associated with
external ethmoidectomy or Caldwell-Luc approach (3). Aggressive resection of the
medial and inferior orbit in severe disease can be vision sparing but promotes medial and
inferior rotation of each globe. Mucoceles can form after these procedures and should be
sought before they become a problem.
Endoscopic Intranasal Dacryocystorhinostomy
A lower success rate of approximately 75% to 85% for endoscopic intranasal
dacryocystorhinostomy (EIDCR) as opposed to more than approximately 90% to 95% for
open dacryocystorhinostomy and decreased familiarity with EIDCR have led to
decreased acceptance of EIDCR among ophthalmologists. The success of open
dacryocystorhinostomy is independent of the postoperative care needed for successful
EIDCR. However, an endoscopic approach allows preservation of the lacrimal apparatus,
spares the patient an external incision, and may reduce operative time. Endoscopic
intranasal dacryocystorhinostomy may be particularly useful to patients who have
undergone unsuccessful external dacryocystorhinostomy. Endoscopic intranasal
dacryocystorhinostomy begins with an incision in the mucosa over the agger nasi in the
region of the lacrimal bone. The bone over the sac is removed with a drill. The lacrimal
sac is identified, and the medial portion of the sac is excised and marsupialized. The
position of the agger nasi and uncinate process helps identify the anterior portion of the
lacrimal fossa without a light probe advanced through the lacrimal system.
Endoscopic Marsupialization of Mucoceles
Mucoceles can recur as long as 43 years after surgery. It therefore may be premature to
profess long-term benefits of this approach. However, mucoceles of the sphenoidal,
ethmoidal, and frontal sinuses have been successfully managed endoscopically.
Endoscopic decompression is probably the best initial therapy for these lesions. This is
particularly true of mucoceles that have eroded the posterior table of the frontal sinus and
become adherent to dura. Complete removal of mucosa in such instances is difficult, and
obliteration often is not possible. Marsupialization of these lesions is best achieved
endoscopically. It is important to remove all osteitic intersinus septa if recurrence of
disease is to be avoided. Bony erosion, proptosis, and diplopia are not contraindications
to the endoscopic approach. Postoperative endoscopic evaluation has revealed that the
lining of these marsupialized cavities has a normal mucosal appearance and that the
cavities have an effective mucociliary clearance pattern. Morbidity with this technique
lower than that of other techniques, and proptosis and diplopia usually resolve rapidly.
Hospitalization usually lasts less than 24 hours. As with other endoscopic sinus
operations, meticulous postoperative care is needed (24).
Lasers
The potassium titanyl phosphate 532 (KTP 532) laser is well suited for soft-tissue
endoscopic surgery for several reasons. The visible laser light (532 nm) has a flexible
fiberoptic delivery system, is preferentially absorbed by red pigment, requires no aiming
beam, and has a limited depth of penetration beyond the site of vaporization. It has been
used with some success for the management of turbinate dysfunction, vascular disorders,
chronic sinus disease, inverted papilloma, and intranasal or intrasinus scarring (25).
Some of the advantages of the KTP 532 laser also are found in the argon laser. The argon
laser can be delivered with a fiberoptic system, is preferentially absorbed by heme
pigments, and requires no aiming beam. The argon laser generates light at two
wavelengths488 nm (blue) and 514 nm (green). The similarity in wavelengths between
the argon and KTP 532 lasers explains the similarities in their other physical properties.
Some surgeons advocate use of a contact yttrium aluminum garnet laser. A carbon
dioxide laser currently has limited role in endoscopic sinus surgery because of an
inability to deliver laser energy through a small fiber. Laser obliteration of nasal
polyposis with a KTP 532 laser is time consuming and has largely been replaced by the
use of powered instrumentation (soft-tissue shavers). Because of the risk of combustion,
oxygen should be near atmospheric pressure while the laser or any cautery device is in
use.
RESULTS
Numerous reports have shown good results of endoscopic sinus surgery for chronic
rhinosinusitis. Short-term symptomatic improvement appears to be independent of both
the extent of preoperative disease and the presence or absence of persistent disease within
the cavity (26). However, the extent of disease at preoperative CT staging is predictive of
the objective resolution of disease with surgical intervention and also has serious
implications for long-term disease recurrence (27).
In a study by Kennedy (26), more than 75% of patients without polyps had normal-
appearing endoscopic cavities after a mean follow-up period of 18 months. However,
only 23.5% of the cavities with diffuse sinonasal polyposis were normal. A follow-up
study involving 72 patients from the original study group observed for an average of 7.8
years after surgery showed that none of the patients with cavities that returned to normal
needed revision surgery. An interesting finding was that continued smoking adversely
affected disease recurrence rate. The overall revision rate after more than 7.5 years was
low (18%) even though 75% of the patients had undergone previous nasal or sinus
surgery and some patients had undergone several previous surgical procedures
(maximum 13) (27). Thirty of the 72 patients had a history of asthma. Ninety percent of
the patients with asthma reported continued gradual alleviation of asthma. Although the
investigators reported a 49% average rate of relief of symptoms 1.1 years after the
operation, this increased to an average of 65% symptomatic improvement in asthma 6.5
years after surgical intervention.
The results for long-term improvement of nasal and sinus symptoms are excellent. In one
study, 98.4% of patients reported overall improvement. However, when patients are
asked to rank the degree of relief of specific symptoms, marked variation is found from
symptom to symptom. In our study, the degree of symptom relief was highest for
headache and facial pain (68%) and lowest for improvement in olfaction (52%).
The low degree of morbidity associated with functional endoscopic sinus surgery and
excellent reported subjective results have made this type of surgery the best approach to
chronic inflammatory sinus disease that fails medical management. There appears to be
no doubt that meticulous surgical technique aimed at mucosal preservation and removal
of all bony partitions in the areas of disease and careful postoperative management can
substantially affect nasal and sinus symptoms and quality of life. The good results should
not lead to overenthusiasm for surgical intervention. Rhinosinusitis is a multifactorial
disease for which the primary mode of therapy remains medical management. All
surgical series report the results of surgery combined with medical management. In most
cases, we recommend that surgery be regarded adjunctive to environmental and medical
management of rhinosinusitis.

HIGHLIGHTS
Diagnosis of nasal and paranasal sinus disease, not its direct
application to surgery, is the most important aspect of nasal
endoscopy.
Anatomic variations within the paranasal sinuses are not
indications for surgery, but they can predispose patients to sinus
disease.
A thorough understanding of the normal anatomic features of
the paranasal sinuses and the variations is essential to prevent
complications of sinus surgery.
Endoscopic sinus surgery is an excellent approach to the
management of diseases of the nose and paranasal sinuses, but
it may not be the best technique for every otolaryngologist.
Coronal CT evaluation of the paranasal sinuses is essential for
planning surgery. The absence of pathologic changes on a CT
scan is not an absolute contraindication to surgery if the history
and nasal endoscopic findings indicate a need.
Patients with chronic sinus disease are candidates for surgery
after an adequate trial of maximal medical therapy has failed.
Surgery is not an alternative to medical management.
Endoscopic sinus surgery is contraindicated unless the surgeon
and patient are committed to meticulous, postoperative
endoscopic dbridement.
Extramucosal fungal rhinosinusitis seems to be more prevalent
than had been previously recognized.
Complications of sinus surgery can be disastrous and should be
discussed frankly with each patient. Endoscopic sinus surgery
for chronic sinus disease is elective.
More than 90% of patients report overall improvement in sinus
and nasal symptoms after functional endoscopic sinus surgery;
this high percentage can be sustained for more than 7.5 years
with appropriate follow-up care.
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results. Otolaryngol Head Neck Surg 1999;120:678682.
22. Swanson P, Lanza DC, Kennedy DW, et al. The effect of middle turbinate resection upon frontal
sinus disease. Am J Rhinol 1995;9:191195.
23. Bolger WE, Parsons DS, Mair EA, et al. Lacrimal drainage system injury in functional endoscopic
sinus surgery: incidence, analysis, and prevention. Arch Otolaryngol Head Neck Surg
1992;118:11791184.
24. Kennedy DW, Josephson JS, Zinreich SJ, et al. Endoscopic sinus surgery for mucoceles: a viable
alternative. Laryngoscope 1989;99:885.
25. Levine HL. Endoscopy and the KTP/532 laser for nasal sinus disease. Ann Otol Rhinol
1989;98:46.
26. Kennedy DW. Prognostic factors, outcomes, and staging in ethmoid sinus surgery. Laryngoscope
1992;102[Suppl]:118.
27. Senior BA, Kennedy DW, Tanabodee J, et al. Long-term impact of functional endoscopic sinus
surgery on asthma. Otolaryngol Head Neck Surg 1999;121:6668.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

33 APPROACHES TO THE SPHENOIDAL SINUS
Head & Neck SurgeryOtolaryngology
33




APPROACHES TO THE SPHENOIDAL SINUS
RAYMOND L. WEISS, JR.
BYRON J. BAILEY

R.L. Weiss, Jr.: Bay Area ENT, Ocean Springs, Mississippi.
B.J. Bailey: Department of Otolaryngology, University of Texas Medical Branch at Galveston, Galveston,
Texas.


Anatomy
Preoperative Evaluation
Transsphenoidal Hypophysectomy
Transseptal Approaches
Sublabial Transseptal Approach
Intranasal Transseptal Approach
External Rhinoplasty Transseptal Approach
Columellar Flap Modification
Previous Septal Surgery
Transantral Approach
Transethmoidal Approach
Sphenoid Inflammatory Disease
Endoscopic Approaches to the Sphenoid Sinus
Intranasal Sphenoethmoidectomy
Transantral Sphenoethmoidectomy
Sphenoid Tumors
Transpalatal Approach
Sphenoidal Mucocele
Complications
Emergencies
New Frontiers
Chapter References
Occupying the most central portion of the head, the sphenoidal sinus has been called the
silent sinus. Vague symptoms are the norm, because this sinus is the most common site of
overlooked disease in the head and neck. Sophisticated radiographic techniques have
opened a window on this region and allowed earlier diagnosis and competent
pretreatment evaluation. Operating microscopes, intraoperative radiofluoroscopy, and
advanced microsurgical instruments have increased the effectiveness and scope of
surgical treatment. These approaches are grouped by the disease warranting surgery
transsphenoidal hypophysectomy, sphenoidal inflammatory disease, and sphenoidal
tumors.
ANATOMY
The sphenoidal sinus is the most posterior of the paranasal sinuses. The sinus develops
with pneumatization of the sphenoid bone, which progresses rapidly between 5 and 7
years of age. Pneumatization is complete by 20 to 25 years. Three types of
pneumatization have been described (Fig. 33.1). The sellar type is most common (86%);
a sellar floor bulges into a well-developed sinus. Sellar pneumatization is the ideal
anatomic configuration for transsphenoidal hypophysectomy because the floor bulges
into direct view of the operative field. In the presellar type (11%) of pneumatization,
cancellous bone of the sphenoid extends from under the sella turcica to the anterior aspect
of the floor. Least common (3%) is the conchal type of pneumatization, in which the
sphenoidal sinus is almost absent and is entirely filled with cancellous bone. This is not
an absolute contraindication to transsphenoidal hypophysectomy, because the bone can
be drilled to allow access. Incompletely pneumatized sphenoidal sinuses are more
commonly encountered in transsphenoidal surgery for pituitary adenoma among children
(1).

FIGURE 33.1. Hamberger classification of sphenoidal
pneumatization.



In all but the conchal variety of pneumatization, the result is an unequal pair of sinuses
the bony septum is rarely in the midline. The sinuses can be extremely asymmetric, one
much larger and overlapping the other. There may be more than one septum, and
commonly no communication exists between the sinuses. The sinus can extend beyond
the body of the sphenoid bone into the base of the sphenoid wing or pterygoid processes
or even into the basiocciput. A posterior ethmoidal sinus can extend into the body of the
sphenoid bone and largely replace the sphenoidal sinus.
The anterior wall of the sinus is thin and opposes the sphenoethmoidal recess of the
posterior nasal space. Approximately one half to one third of the way up this wall is a
pair of foramina that flank the midline sphenoidal crest. The anterior border of this crest
articulates with the perpendicular plate of the ethmoid bone. The inferior surface of the
sphenoid body projects into the median plane as the sphenoidal rostrum, which articulates
with the vomer. The floor of the sinus forms a portion of the anterior roof of the
nasopharynx and can contain the bony projection of the pterygoid canal. In the posterior
aspect beyond the thin cortical wall is the cancellous bone of the sphenoid contribution to
the clivus.
Lateral to the sphenoidal sinus lies the cavernous sinus with its myriad of interlacing
venous channels, the internal carotid artery, and the following cranial nerves: oculomotor,
trochlear, abducent, ophthalmic, and to a lesser degree the maxillary branches of the
trigeminal. The internal carotid artery often indents the posteroinferior surface of the
lateral sphenoidal sinus wall as a bony ridge. Anatomic studies showed that 71% of 50
cadavers had extremely thin overlying bone, whereas 4% had no bone covering the
carotid artery. The abducent nerve travels in close association with the lateral wall of the
artery in its ascending and initial vertical course. The rest of the cranial nerves are more
lateral in the sinus (Fig. 33.2).

FIGURE 33.2. Coronal section through midsphenoid
shows cavernous sinus and sphenoidal sinus contents and
relations.



The sella turcica produces a marked bulge in the roof of the sphenoidal sinus, and the
optic chiasm straddles the pituitary infundibulum. As it proceeds anteriorly, each optic
nerve passes through the optic canal, which is in the anterolateral aspect of the sphenoidal
roof. The bone of the optic canal can be extremely thin or be absent (4%) with the optic
nerve covered only by the optic nerve sheath and sinus mucosa.
PREOPERATIVE EVALUATION
When the need for sphenoidal sinus surgery is established, a thorough preoperative
evaluation is needed. A carefully acquired history of nasal and sinus symptoms is the
cornerstone of the evaluation. Pertinent historical features include previous nasal surgery
or trauma, chronic nasal or sinus infection, persistent nasal problems, such as obstruction,
nasal discharge, epistaxis, septal perforation, and nasal discomfort, or headaches (2). Any
history of denture use, capped teeth, or anterior incisor root canal surgery should be
ascertained. Intranasal examination should assess the anatomic features of the septum and
any evidence of nasal or sinus infection. Active sinus infection is the main
contraindication to a transnasal intracranial procedure. Nasal culture provides a helpful
preliminary guideline to treatment if the patient has a postoperative fever due to infection
of the sinuses or meninges.
Plain radiographs of the sinuses are obtained to assess the extent of sellar pneumatization
and any sign of acute infection. Sinus protocol computed tomography (CT) with contrast
enhancement provides further information on the anatomic features of the sinuses, such
as intersinus septal position. Sinus CT also is used to assess bony destruction and the
extent of paranasal sinus disease. Chronic fungal infection causes a radiographic
appearance that can mimic mucocele or tumor. Magnetic resonance imaging can help
differentiate tumor mass from pus or mucus and help assess intracranial involvement.
Marked tumor enhancement warrants angiography to rule out vascular lesions (Table
33.1).

TABLE 33.1. PREOPERATIVE EVALUATION



TRANSSPHENOIDAL HYPOPHYSECTOMY
Resection of pituitary tumors through the transseptal transsphenoidal approach was
pioneered by Cushing and Hirsch in 1910. However, by 1930, the transcranial approach
was adopted by Cushing and by most U.S. surgeons because they could not remove
suprasellar lesions from below. The transseptal approach remained popular in Europe.
Antibiotics and steroids made total hypophysectomy safer by all routes during the 1950s.
Hardy eventually repopularized the transseptal transsphenoidal technique in the United
States, and today it is the most common method to expose the sphenoidal sinus for
hypophysectomy. The transantroethmosphenoidal and external transethmosphenoidal
routes are other nonintracranial approaches to the pituitary gland.
Transseptal Approaches
The transseptal approach is useful for a variety of lesions, ranging from pituitary
microadenoma to much larger tumors. Pituitary microadenoma can be removed totally
and normal pituitary tissue preserved. This technique frequently is preferable to medical
treatment, even when the only abnormality is an endocrine disorder. In operations on
large pituitary neoplasms with extensive suprasellar involvement, the transseptal
approach is best. Total removal of these tumors often is impossible, but tissue diagnosis
and decompression of the optic chiasm can be obtained. The intrasellar portion of the
tumor is removed, and the remaining tissue slowly decompresses into the operative field.
This decompression is facilitated by normal brain pulsation, the use of a Valsalva
maneuver by the anesthesiologist, or injection of saline solution into the cerebrospinal
fluid (CSF). There are several variations of this approach. The more frequently used
methods are compared in Table 33.2. The sublabial approach is the most popular
transseptal procedure.

TABLE 33.2. COMPARISON OF TRANSSEPTAL
APPROACHES



Sublabial Transseptal Approach
After general anesthesia is induced, 1% lidocaine with 1:100,000 epinephrine is injected
into the upper buccal sulcus and into the septum and floor of the nose. An incision is
made into the upper labial sulcus approximately 5 mm superior to the junction between
the gingiva and the mucosa and carried down to the bone (Fig. 33.3A). Premaxillary
periosteum is elevated to the inferior margin of the piriform aperture, and the anterior
nasal spine is exposed. Bone from the piriform aperture and the nasal spine is resected as
needed for exposure. The perichondrium is incised over the caudal end of the right side of
the nasal septum. The mucoperiosteum is elevated from the inferior lip of the piriform
aperture and the floor of the nose bilaterally. The dissection is carried farther on the right
side along the lateral wall of the maxillary crest and then superiorly along the right
cartilaginous and bony septum. The mucosa left of the nasal floor is elevated in a similar
manner, but the left septal mucosa is left intact. The cartilaginous septum is dislocated
from the perpendicular plate and maxillary crest and displaced into the left naris. The
perpendicular plate of the septum is removed until only the vomer remains to expose the
rostrum of the sphenoid bone. A neurosurgical pituitary speculum is inserted, and
fluoroscopy is performed to confirm proper positioning. The sphenoidal sinus is entered
in the midline under guidance of an operating microscope. The sphenoidal ostia are used
initially as the superior and lateral landmarks for safe removal of the anterior sinus wall.
The septa are resected and the mucosal lining is removed if the surgeon plans to graft the
sinus with fat.

FIGURE 33.3. Transseptal approaches. A: Sublabial
incision. B: Intranasal transseptal incisions. A,
Hemitransfixation or Freer; B, Killian; C, vertical; D,
bony-cartilaginous junction. C: External rhinoplasty
incisions. D: Columellar flap modification.



After the surgical procedure, the sphenoidal sinus can be closed in one of several ways,
such as packing the sinus with fat or muscle and use of a septal bone graft and possibly
fibrin glue. The mucoperiosteal and mucoperichondrial septal flaps are reapproximated
with emphasis on interposing as much bone or crushed cartilage as possible to ease
subsequent reoperation. The cartilaginous septum is placed back into the maxillary crest
groove, and its caudal aspect is sutured to the anterior nasal spine. The sublabial incision
is closed in the standard manner, and the nose is packed.
Various modifications of sublabial transseptal transsphenoidal hypophysectomy have
been proposed. A common modification of the purely sublabial approach is
hemitransfixion septal incision with subsequent development of septal and nasal floor
mucosal flaps before the actual labial sulcus incision. This approach allows dissection of
the septa and nasal floor in a manner to which the surgeon is accustomed, and is usually
more rapid. The septal mucosal incision is sutured at the completion of the procedure.
Intranasal Transseptal Approach
A septal incision can be used for direct access to the sphenoidal sinus. Several mucosal
incisions have been proposed, including hemitransfixion, Killian, vertical, and bony-
cartilaginous junction (Fig. 33.3B). This approach allows quick access to the rostrum;
however, lateral alotomy often is needed to gain access for transnasal placement of a
neurosurgical speculum.
External Rhinoplasty Transseptal Approach
After nasal vasoconstriction has been obtained, the columella, external nasal skin,
septum, and nasal floor are infiltrated with 1% lidocaine and 1:100,000 epinephrine. A
standard external rhinoplasty incision is made, and the columellar flap is raised onto the
nasal dome (Fig. 33.3C). The elevation is carried only midway over the lower lateral
cartilages because the exposure needed is less than that needed for rhinoplasty. The
medial crura are separated by means of incision of the intercrural ligaments to expose the
caudal edge of the quadrilateral cartilage. The traditional transseptal approach then is
continued. A new technique has been described in which the medial crura are transected
several millimeters above the skin incision by means of upward dissection of the
columellar skin. This approach avoids extensive tissue dissection and postoperative
edema and provides excellent exposure (3).
Columellar Flap Modification
Peters and Zitsch have described a simple technique that allows extensive access to the
caudal quadrilateral cartilage and nasal floor without separation of the mesial crura of the
lower lateral cartilages (external rhinoplasty technique) or an additional alotomy incision
(direct transseptal approach). A complete transfixion incision is made caudad to the
quadrilateral cartilage through the membranous septum. The incision extends from the
domes superiorly to the nasal spine inferiorly. A transverse incision is carried posteriorly
around the feet of the mesial crura on both sides to join the transfixion incision (Fig.
33.3D). The columellar base is dissected free of the underlying labial soft tissue, and the
columellar flap containing the mesial crura is raised to expose the quadrilateral cartilage.
The traditional transseptal approach is continued.
Previous Septal Surgery
Previous septal surgery typically produces areas where the septal mucosa of one side is
directly adherent to mucosa of the opposite side owing to missing cartilage or bone.
Sawyer (4) described three surgical strategies to avoid septal perforation. First,
septoplasty with avoidance of the problem area relies on traditional septoplasty
techniques to go around the scar tissue. When the small troublesome area is high and
anterior, a standard sublabial transseptal approach can allow going under the scar. More
commonly the scarred septum is inferior, which allows the surgeon to go over the area
with an external rhinoplasty approach.
The second strategy is septoplasty with dissection through adherent mucosal areas.
Factors such as time since the earlier operation, thickness of tissue, and skill of the
surgeon influence the practicality of this choice. This approach usually is feasible when
reoperation is needed soon after the initial procedure, as in the case of CSF leak. Delicate
dissection of the scar can quickly determine the advisability of this technique.
Finally, lateral displacement of the septum allows the surgeon to go around the
troublesome area and is the method chosen most often. This technique is similar to the
transnasal transseptal approach described earlier and can be combined with a sublabial
approach. An incision paralleling the septum is made laterally in the mucosa of the floor
of the nose, near the inferior turbinate (Fig. 33.4). This incision is joined to a complete
transfixion incision that is extended laterally along the piriform margin on both sides. The
mucoperiosteum of the nasal floor is elevated bilaterally, and the caudal septum is
dissected free of the remaining maxillary crest and anterior nasal spine. Dissection is
carried posteriorly until solid bone is encountered. Almost always some septal bone
(vomer) has been preserved below the sphenoidal sinus, even after previous transseptal
sphenoid surgery, and this bone is valuable for surgical orientation. A sublabial incision
is made at this time if needed. A self-retaining retractor is inserted just distally to the
remaining bony septum to displace the mobile portion of the septum and the attached
floor mucosa laterally. The leading edge of residual bone is palpated, and a mucosal
incision is made at this site. Bilaterally mucoperiosteal flaps are made with dissection to
the sphenoidal rostrum.

FIGURE 33.4. Lateral displacement of the septum for
transseptal transsphenoidal hypophysectomy on a patient
who has undergone previous septal surgery. A mucosa-
relaxing incision is made on the floor of the nose. Dotted
line, posterior residual bony septum.



Transantral Approach
The transantroethmoidal approach to the sphenoidal sinus was developed for the
management of sphenoid inflammatory disease. Transantral hypophysectomy was
popularized by Hamberger in the early 1960s but is not commonly used at present. This
approach allows the widest exposure and is 1 to 2 cm closer to the sphenoidal sinus than
is the transseptal approach. However, the oblique angle of the approach provides a
confusing perspective and is associated with increased risk of damage to the contents of
the cavernous sinus, optic nerve, and anterior cranial fossa. Sabit et al. (5) described a
transmaxillary transsphenoidal approach to the sellar and infrasellar region that offers
visualization of the carotid artery, the pituitary fossa, and the cranial nerves of the
cavernous sinus. This approach avoids craniotomy or violation of the nasal cavity when it
is necessary to access vascular or invasive lesions in this region.
Transethmoidal Approach
There are two transethmoidal approaches to the sphenoidal sinusexternal and
intranasal. Only the external route is appropriate for hypophysectomy. The intranasal
approach is used primarily for extensive nasal polyposis and is described later. External
transethmosphenoidal hypophysectomy provides the advantage of the shortest route to
the sinus and avoids postoperative anesthesia of the teeth. However, this approach is
oblique and has the same disadvantages as the transantroethmoidal route as well as the
need for an external incision. This method is not currently popular.
SPHENOID INFLAMMATORY DISEASE
The most common disease of the sphenoidal sinus is sinusitis. Acute and chronic
inflammatory disease of the sphenoidal sinus typically involves the surrounding sinuses,
but isolated sphenoidal disease is encountered occasionally. Intranasal and transantral
sphenoethmoidectomies are the classic approaches to inflammatory disease of this region.
However, the use of endoscopes has changed many aspects of nasal surgery, includ-ing
sphenoidal surgery. For patients with relatively normal intranasal structures, endoscopic
management of sinus disease usually is safe and effective in reducing the morbidity
associated with sphenoidal sinusitis (6). For patients with previous sinus surgery or
extensive disease that has distorted the intranasal landmarks, the classic approaches are
believed to be safer.
Endoscopic Approaches to the Sphenoid Sinus
The endoscopic approach to the sphenoidal sinus varies with the type and extent of
disease. The procedure can be performed with general or local anesthesia. Cotton
pledgets with cocaine solution are placed intranasally for vasoconstriction and analgesia.
The septum, middle and inferior turbinates, and uncinate process are injected with 1%
lidocaine with 1:100,000 epinephrine, and the patient is draped with both eyes in full
view.
If the disease involves the ethmoidal sinuses, a traditional approach is undertaken. The
middle turbinate is medialized or partially resected to give access to the uncinate process.
Infundibulectomy reveals the bulla ethmoidalis, which is opened. Exenteration is carried
out in the anterior and posterior ethmoidal cells. At this point, the angle of dissection
relative to the anterior nasal spine (45%) must be changed, because the sphenoidal sinus
lies at the medial inferior portion of the posterior ethmoid cell. The anterior wall of the
sphenoidal sinus is approximately 7 cm posterior to the anterior nasal spine. This can be
measured with a marked probe (Fig. 33.5). The sphenoidal sinus is entered by means of
gentle probing of the anterior wall with a suction cannula at a 30-degree angle to the
nasal spine. The opening is enlarged with an upward- or back-biting forceps, and great
care is taken in manipulation of the superior and lateral walls. Measurement to the
posterior nasopharyngeal wall with a probe approximates the distance to the posterior
wall of the sphenoidal sinus (approximately 9 cm).

FIGURE 33.5. Measurement and angle of approach to
the anterior wall of the sphenoidal sinus relative to the
anterior nasal spine.



If the patient has isolated sphenoidal sinus disease, an alternative approach can be used.
After the patient is prepared for surgery, the middle turbinate is fractured toward the
septum. Endoscopic scissors are used to make two incisions, anterior superior and
posterior inferior, in the middle turbinate with subsequent removal of this tissue. The
grand lamella is the remaining posterior attachment of the middle turbinate, and the
posterior ethmoidal cells are entered through this thin bony wall. A 0-degree telescope
and upward- and straight-biting forceps are used for access. In the lateral aspect, the
natural ostia of the maxillary sinus often are visualized. At this point, the anterior wall of
the sphenoidal sinus is encountered and opened. Because of the lateral entrance to the
sphenoid, great caution is exercised to avoid injury to the carotid artery and optic nerve.
Intranasal Sphenoethmoidectomy
Intranasal sphenoethmoidectomy is an important option in the management of
hyperplastic nasal and sinus disease. It is preferred by some surgeons for treating patients
with recurrent nasal polyps, hyperplastic rhinosinusitis with asthma, and chronic purulent
ethmoiditis. The operation can be performed with general or local anesthesia. The face is
fully exposed, and vasoconstriction is achieved with cocaine solution and epinephrine.
The middle turbinate is infractured after removal of any polyps. A Glasgow forceps is
used to enter the middle ethmoid cells. Attention is given to remaining in a plane parallel
to the nasal fossa and avoiding excessive force when excising bone fragments. The
middle turbinate forms the medial boundary. The orbital wall is the lateral limit as the
dissection is continued posteriorly to the posterior attachment of the middle turbinate.
This structure is then pushed laterally, and any polyps are removed from the medial
aspect.
If polypoid degeneration necessitates removal of the middle turbinate, the base is
preserved as an important landmark. With continued dissection medial to the turbinate,
the sphenoidal sinus orifice is encountered. Often the orifice is covered with polyps but
can be identified by gently probing with the Fraser suction posterior and slightly superior
to the posterior attachment of the middle turbinate. The anterior sphenoid wall is about 7
cm posterior to the anterior nasal spine at an angle of 30 degrees from the nasal floor. The
ostium is enlarged toward the midline with Kerrison forceps after removal of the
overlying polypoid mucosa, and polyps in the sinus are cleared carefully. The posterior
attachment of the middle turbinate is removed, and exenteration of the posterior ethmoid
cells is performed within the plane of the lateral sphenoid wall. This produces a common
cavity of the sphenoidal and posterior ethmoidal cells. The anterior ethmoidal cells are
removed with an up-biting forceps. Care is taken to remain in a plane lateral to the
middle turbinate.
Transantral Sphenoethmoidectomy
Transantral sphenoethmoidectomy is used by some surgeons to manage chronic
hyperplastic disease, especially if extensive benign maxillary disease encroaches on the
ethmoidal and sphenoidal sinuses (7). This approach, excluding exposure of the
sphenoidal sinus, also is useful for orbital decompression. After anesthesia and
vasoconstriction have been obtained, the antral cavity is entered through a sublabial
canine fossa approach. An incision is made into the superior labial sulcus, and the soft
tissues over the anterior wall of the maxilla are retracted. The anterior maxillary wall is
widely opened, including bone between the infraorbital nerve and nasal bone. Antral
mucosal disease is addressed with removal of mucosa thought to be irreversibly changed.
The middle turbinate, landmark to the ethmoidal and sphenoidal sinuses, is exposed by
means of removal of the nasoantral wall. A measurement probe can be introduced
nasally, as previously described, immediately above the posterior tip of the middle
turbinate and directed medially toward and parallel to the turbinate to identify the anterior
sphenoid wall. After this dissection, the anterior sphenoid wall is opened to expose the
sinus.
If the approach is for access to the sella turcica, the posterior part of the ethmoid plate can
be resected with a portion of the vomer to expose the entire bulge of the sella. If the
approach is for management of polypoid pansinusitis, exenteration of the ethmoidal
labyrinth is performed with an up-biting forceps from posterior to anterior. The dissection
must remain lateral to the middle turbinate and at the same tegmen level to avoid
fracturing the cribriform plate or penetrating the ethmoidal tegmen. The intranasal
approach can be used with the transnasal approach to assist in removing the more anterior
cells and improve the orientation and completeness of the operation (8).
SPHENOID TUMORS
Benign and malignant, primary or metastatic tumors can occur in the sphenoidal sinus.
The transseptal, transethmoidal, or endoscopic approach can be used for tumor resection,
along with the transpalatal approach that follows. Rarely are the tumors isolated to the
sphenoidal sinus alone, thus involvement and exposure of contiguous structures must be
considered in decisions about the appropriate approach. Sphenoclival tumors, such as
primary or recurrent chordoma, chondrosarcoma, and petroclival cyst, can be accessed
through the transsphenoethmoid approach combined when necessary with medial
maxillectomy (9). Malignant neoplasms and benign tumors with aggressive, locally
invasive features and involving the sphenoidal sinus in the past have been considered
inoperable and incurable. Yet as methods have been developed to manage hemorrhage
from the cavernous sinus, to expose and control or bypass the internal carotid artery, and
to perform combined subcranial and intracranial resection, the frontiers of surgery in the
sphenoidal sinus have been expanded to include many patients with advanced tumors.
Transpalatal Approach
Tumors of the base of the skull can be approached through the palate alone or in
combination with another approach. Neoplasms of the nasopharynx, posterior pharyngeal
wall, and choanae are suitable for this approach. Tumors isolated to the sphenoidal sinus
and sella are better resected with alternative methods, such as transseptal or
transethmoidal approaches, unless the tumor extends into the nasopharynx, in which case
the transpalatal route is preferable.
There are several variations of the transpalatal approach. In each of the techniques, the
tongue and endotracheal tube are retracted with a Crowe-Davis or Dingman retractor,
which should be released from time to time during the procedure to avoid postoperative
lingual edema and possible necrosis. Dibble and King described the midline palatal split
in which the palate is divided along its medial raphe (Fig. 33.6A). The hard palate is
removed as necessary to gain adequate exposure to the nasopharynx. The posterior vomer
is resected as necessary with exposure of the rostrum and sphenoidal sinus. A linear
incision or mucosal flap can be made in the posterior pharyngeal wall to expose the
retropharyngeal structures as needed. It is difficult to achieve watertight closure of the
posterior pharyngeal wall. Thus dural entry should be avoided whenever possible in the
transpalatal approach. The palate is closed in two layers, muscle and nasal mucosa first,
followed by the oral mucosa. This technique is the quickest and easiest to perform with
good exposure and flap viability; however, it can lead to palatal shortening and
velopharyngeal insufficiency.

FIGURE 33.6. Incision variations for transpalatal
approaches to the base of the skull. A: Midline (Dibble
and King). B: Bipedicle (Mullan). C: S-shaped
(Kennedy).



Mullan described an alternate technique that involves a U-shaped incision at the junction
of the soft and hard palate (Fig. 33.6B). The resulting bipedicled flap, attached by the soft
palate laterally, is pulled down toward the tongue with a Crowe-Davis retractor. The hard
palate is resected for exposure as previously described. At the completion of the
procedure, the incision is closed in two layers. This technique preserves palatal motor
function best, but exposure is limited inferiorly, and stretching of the soft palate by the
retractor can cause ischemia and swelling.
A third approach, developed by Kennedy, relies on an S-shaped incision originating
along the lingual alveolus and curving back across the palatal aponeurosis to divide the
soft palate off the midline (Fig. 33.6C). The anterior portion of the incision is posterior to
the incisive canal; thus flaps are based on the two greater palatine vessels. The S-shaped
incision gives excellent exposure but avoids the possibility of palatal contracture that
occurs with midline incisions. Closure is more difficult because of a longer incision and
the increased thickness of the lateral soft palate.
Sphenoidal Mucocele
The most common space-occupying lesion of the sphenoidal sinus is the mucocele.
Transseptal techniques have been used frequently in the past, but the use of the
endoscopic approach has continued to increase and expand to meet the challenges of
more complex tumors. The transsphenoidal endoscopic approach has proved successful
in the management of sphenoidal and ethmoidal mucoceles with orbital and intracranial
extension and with cholesterol granuloma of the petrous apex (10). The most important
factor in preventing recurrence is providing wide-open drainage for the mucocele.
Ghorayeb described a modification of the transseptal approach that helps to achieve this
goal. After the standard transseptal approach has been performed and the anterior wall of
the sphenoidal sinus has been entered, this opening is enlarged with a rongeur. The
pituitary speculum is withdrawn about 2 cm, and a vertical incision is made in the
mucoperiosteal flap. This incision is enlarged superiorly and inferiorly, resulting in a
posteriorly based U-shaped flap. The flap is rotated posteromedially to line the inner wall
of the sphenoidal sinus (Fig. 33.7). Fibrillar absorbable hemostat or gelatin foam sponge
is packed lightly in the sinus to keep the new mucous membrane flap in position.

FIGURE 33.7. Ghorayeb technique for ensuring
adequate drainage of sphenoidal mucocele. A: Sinus
mucosa and intersphenoidal septum removed. U-flap
rotated into sinus. B: Postoperative appearance with
window in the face of the sphenoid bone.



COMPLICATIONS
Complications are related to the nasal, neurologic, and vascular aspects of the operation.
Nasal complications are primarily cosmetic and include saddle and tip deformities. Septal
perforations, infections, and epistaxis from intranasal sources also can occur. Neurologic
and vascular complications are commonly related to the complex anatomic relations in
the region. Dehiscence of the medial cavernous sinus wall or protruding vessels or optic
nerve can predispose a patient to injury to these structures during procedures involving
anything more extensive than opening the anterior wall of the sinus. In addition to injury
to the contents of the cavernous sinus, intracranial complications include trauma to the
optic chiasm, chiasmal compression from fat packing, late prolapse of the chiasm into the
decompressed sella, and direct trauma to the hypothalamus. Cerebrospinal fluid leaks can
occur and must be controlled vigorously when first found. Any unexplained neurologic
change or hemorrhage in the postoperative period necessitates immediate intervention.
Radiographic imaging, CT, and occasionally arteriography often reveal the cause (Table
33.3).

TABLE 33.3. COMPLICATIONS SPHENOID
SINUS SURGERY



EMERGENCIES
Emergencies necessitating immediate sphenoid surgery pertain to neurologic or
ophthalmic complications. Acute, aggressive sphenoidal sinusitis associated with the
development of meningitis or other neurologic signs is an emergency, and drainage of the
sinus must be undertaken. The development of vision loss in association with a sellar or
parasellar tumor is an emergency that necessitates surgical therapy or radiation therapy
depend-ing on the tumor. Operative emergencies commonly relate to ophthalmic or
vascular complications. Endoscopic or other transethmoidal approaches to the sphenoidal
sinus can cause retrobulbar hemorrhage and eventual blindness due to the injury of
orbital fat blood vessels. The patient's eyes should be visible in the operative field.
Intraoperative proptosis is managed by means of lateral canthotomy and ophthalmic
consultation. Intraoperative hemorrhage from the sphenoidal sinus region is controlled
initially with packing and pressure followed by reexploration. Continued bleeding that
cannot be controlled or fully exposed operatively can necessitate interventional
arteriography with embolization with gelatin foam, springs, or balloons (Table 33.4).

TABLE 33.4. EMERGENCIES SPHENOID



NEW FRONTIERS
Endoscopic surgery in the sellar region can be performed safely and effectively, and it
affords the surgeon with a view that is superior to that obtained with an operating
microscope (11). Use of the endoscopic approach also decreases bleeding during the
operation and shortens operative time and hospital stay (12). The usefulness of three-
dimensional intraoperative imaging for enhancing teaching and safety also has been
emphasized (13).

HIGHLIGHTS
The sphenoidal sinus is called the silent sinus because
symptoms often are vague, and disease in this area is frequently
overlooked.
Important points in the history are previous nasal surgery or
trauma, chronic nasal or sinus infection, obstruction, nasal
discharge, epistaxis, headache, and septal perforation.
Plain sinus radiographs provide screening information.
Computed tomography is used to assess the extent of mucosal
disease and bony destruction. Magnetic resonance imaging
shows intracranial involvement and helps differentiate soft-
tissue shadows.
The transseptal approach to the sphenoidal sinus provides
optimal access and visualization for removal of most pituitary
tumors.
To approach the sphenoidal sinuses of patients who have
undergone septal surgery, the surgical strategies are dissection
along a path that avoids the area of previous surgery, dissection
through the previous operative field in the early postoperative
period, and lateral displacement of the septum, which is most
common.
In addition to the transseptal approach to the sphenoidal sinus,
approach options are transantroethmoidal and external
transethmoidal.
The endoscopic approach to the sphenoidal sinus has become
popular as a means to manage inflammatory disease of the
sphenoidal sinus.
Tumors of the base of the skull can be approached through the
palate, posterior vomer, and sphenoid rostrum.
The most common space-occupying lesion of the sphenoidal
sinus is mucocele. Providing adequate sphenoidal sinus
drainage is essential to preventing postoperative recurrence.
Complications of sphenoidal sinus surgery are related to the
nasal, neurologic, and vascular aspects of the procedures. They
include nasal deformity, damage to the contents of the
cavernous sinus, injury to the optic nerve, and CSF leaks.
Emergencies necessitating sphenoid surgery include acute
sphenoidal sinusitis with neurologic signs and development of
vision loss in association with parasellar tumor. Intraoperative
emergencies include retrobulbar hematoma and hemorrhage
from the sphenoidal sinus.
CHAPTER REFERENCES
1. Dyer EH, Civit T, Visot A, et al. Transsphenoidal surgery for pituitary adenomas in children.
Neurosurgery 1994;34:207212.
2. Wilson WR, Khan A, Laws ER. Transseptal approaches for pituitary surgery. Laryngoscope
1990;100:817819.
3. Arden RL, Pasha R, Guthikonda M. Transcolumellar transcrural approach to transsphenoidal
hypophysectomy. Laryngoscope 1999;109:18801883.
4. Sawyer R. Nasal approach to the sphenoid sinus after prior septal surgery. Laryngoscope
1991;101:8991.
5. Sabit I, Schaefer SD, Couldwell WT. Extradural extranasal combined transmaxillary
transsphenoidal approach to the cavernous sinus: a minimally invasive microsurgical model.
Laryngoscope 2000;110:286291.
6. Metson R, Gliklich RE. Endoscopic treatment of sphenoid sinusitis. Otolaryngol Head Neck Surg
1996;114:736744.
7. Malotte MJ, Petti GH, Chonkich GD, et al. Transantral sphenoethmoidectomy: a procedure for the
1990's. Otolaryngol Head Neck Surg 1991;104:358361.
8. Rosen FS, Sinha UK, Rice DH. Endoscopic surgical management of sphenoid sinus disease.
Laryngoscope 1999;109:16011606.
9. Lalwani AK, Kaplan MJ, Gutin PH. The transsphenoethmoid approach to the sphenoid sinus and
clivus. Neurosurgery 1992;31:10081014.
10. Griffith AJ, Terrell JE. Transsphenoid endoscopic management of petrous apex cholesterol
granuloma. Otolaryngol Head Neck Surg 1996;114:9194.
11. Spencer WR, Das K, Nwagu C, et al. Approaches to the sellar and parasellar region: anatomic
comparison of the microscope versus endoscope. Laryngoscope 1999;109:791794.
12. Koren I, Hadar T, Rappaport ZH, et al. Endoscopic transnasal transsphenoidal microsurgery
versus the sublabial approach for the treatment of pituitary tumors: endonasal complications.
Laryngoscope 1999;109:18381840.
13. Moses RL, Keane WM, Andrews DW, et al. Endoscopic transseptal transsphenoidal
hypophysectomy with three-dimensional intraoperative localization technology. Laryngoscope
1999;109:509512.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

34 SPHENOID SINUS DISEASE
Head & Neck SurgeryOtolaryngology
34




SPHENOID SINUS DISEASE
DANIEL J. RATCLIFF
BRADLEY F. MARPLE

D.J. Ratcliff and B.F. Marple: Department of OtolaryngologyHead and Neck Surgery, University of
Texas Southwestern Medical Center, Dallas, Texas.


Development
Anatomy
Inflammatory Disease
Acute Bacterial Sphenoiditis
Invasive Fungal Sinusitis
Allergic Fungal Sinusitis
Mycetomas
Chronic Sphenoiditis
Mucoceles
Neoplastic Disease
Fibrous Dysplasia
Chordoma
Malignant Tumors of the Sphenoid
Operative Techniques
Open Approaches
Endoscopic Approaches
Conclusions
Chapter References
Diseases involving the sphenoid sinus have presented diagnostic and therapeutic
challenges for decades. Historically, these challenges arose from the vague symptoms
produced by sphenoid sinus disease coupled with its remote location amidst a number of
complicated anatomic structures. Recent improvements in radiographic imaging and
endoscopic examination have helped to better diagnose and treat diseases in this area.
This chapter addresses the basics behind sphenoid sinus anatomy and physiology and the
current diagnostic and treatment modalities of this complex sinus.
DEVELOPMENT
Development of the paired sphenoid sinuses begins early in the third month of fetal
development and continues throughout the first decade of life. Initially, the sinus is seen
as an invagination of the nasal mucosa that extends posteriorly through the cartilagenous
nasal capsule. This creates a pouchlike cavity that ossifies during the fifth month of fetal
development and can be well developed by the time of birth. However, remnant cartilage
interpositioned within the fetal sphenoid sinus is generally not obliterated until the third
or fourth year of life. After age 3, the sphenoid undergoes a gradual but progressive
process of pneumatization. The lateral walls and floor thin out by the sixth or seventh
year, and generally by the tenth year of life medial expansion of the paired sinuses thins
the intersinus septum as well (1). During the entire process of development, expansion of
the sphenoid sinus is uniquely altered within each individual based on the delicate
interplay between the sinus, the various ossification centers within the sphenoid bone,
and the vessels and nerves coursing through the sphenoid bone.
ANATOMY
Solid grasp of sphenoid anatomy is important not only for proper diagnosis but for
successful operative intervention as well. Extension of pathology beyond the sphenoid
sinus into neighboring structures carries the potential for grave results but is often subtle
in nature and easily overlooked without forethought. Similarly, operative interventions
either into or through the sphenoid sinus carry the potential for iatrogenic blindness,
arterial hemorrhage, and cranial nerve palsy. Knowledge of the close anatomic
relationships between this distant sinus and its neighbors is essential before dealing with
disease involving the sphenoid sinus.
The sphenoid sinus is the least accessible of the paranasal sinuses and occupies a position
deep within the skull. In addition to its remote location, both the size and shape of this
sinus vary dramatically from patient to patient. Thus, although the sphenoid sinus
averages roughly 2 cm in each of its dimensions, its wide range of anatomic variation
mandates understanding it in terms of a spectrum of normal variants. The various
structural patterns are traditionally classified by the relationship between the sinus and
the tuberculum sellae. In looking at 289 specimens, Cope (2) found that in approximately
25% of cadaveric specimens the posterior limit of the sphenoid sinus was located anterior
to a basosphenoid plane, whereas in 54% of specimens there was extension by the
pneumatized sinus posterior to this plane. In the remaining 21% of cases the posterior
limit of the sinus fell somewhere in between. Elwany et al. (3) reported that sinuses
located anterior to the basosphenoid plane, or presellar sinuses, rarely have extension
into the surrounding bony structures and tend to be smaller and more rudimentary when
compared with the more expansile postsellar sinuses. They noted that up to 40% of the
postsellar sinuses extended into other areas of the sphenoid bone, most commonly into
either the anterior clinoid process, the greater wing of the sphenoid, or the pterygoid
process.
Levine (4) estimated that 13 sensitive structures either rest beside or pass near the walls
of the sphenoid sinus (Table 34.1). Although the tuberculum sellae makes up the roof of
the sphenoid sinus, both the floor of the sinus and anterior wall contact the nasopharynx.
The anterior portion of the sinus also abuts the contents of the superior orbital fissure and
the anterior extension of the optic nerve (4). Posterior to the sinus lay the pons and basilar
artery. The cavernous sinus is lateral to the sphenoid sinus and contains the internal
carotid artery and the oculomotor, trochlear, abducent, ophthalmic, and maxillary nerves
(Fig. 34.1). The walls of the sphenoid sinus reflect the impact of this myriad of
neighboring structures through a variety of depressions and elevations.

TABLE 34.1. NEIGHBORING STRUCTURES OF
THE SPHENOID SINUS



FIGURE 34.1. Cadaveric computed tomography. Note
the optic nerve (large single arrow), the internal carotid
artery within the cavernous sinus (double arrow), the
foramen rotundum filled with the maxillary branch of the
trigeminal nerve (small single arrow), and the extensive
pneumatization of the anterior clinoid processes.



The structure that creates changes most frequently in the sphenoid sinus wall is the
internal carotid artery. Located within the medial aspect of the cavernous sinus, the
internal carotid artery passes directly across the lateral wall of the sphenoid sinus and
commonly produces a medial deflection of the lateral wall into the lumen of the sinus.
This deflection is referred to as the carotid sulcus and is present in 65% to 98% of sinuses
(Fig. 34.2). The carotid sulcus tends to be more pronounced within more pneumatized
sphenoid sinuses. The bone that separates the internal carotid from the sphenoid sinus is
thin, almost always less than 1 mm and frequently less than 0.5 mm. Commonly, the wall
is thinnest directly below the tuberculum sellae, and up to 10% of the time areas of bony
dehiscence (Fig. 34.3) can be identified along the internal carotid's course against the
sphenoid sinus wall (5).

FIGURE 34.2. Endoscopic view of the optic canal
(single arrow) and carotid sulcus (double arrow).



FIGURE 34.3. An example of a de novo carotid canal
dehiscence.



In a cadaveric study, Waridel et al. (6) used dynamometers to measure the stress
resistance of the bony sphenoid sinus walls. On average, the bone overlying the carotid
canal provided only minimal protection, just slightly stronger than the terrifyingly thin
eggshell.
In addition to the internal carotid, the optic canals are also intimately related to the
sphenoid sinus, resting against the superiolateral wall (Fig. 34.2). Multiple studies have
demonstrated that the optic canal projects less commonly into the sphenoid sinus lumen
than the internal carotid artery; however, this projection still occurs roughly 50% of the
time. Interestingly, because the paired sphenoid sinuses are frequently dramatically
asymmetric, it is not unusual for a single sinus to come in contact with both optic canals,
a finding that can be documented on up to 10% of computed tomographies (CTs) (7). As
with the carotid canals, the optic canals are usually covered with only a thin layer of
bone, usually less than 0.5 mm. In many sinuses, the bone overlying the optic canals
becomes increasingly dehiscent with increasing age.
Although the carotid and optic canals commonly alter the shape of the sphenoid air cells,
the effects of other structures can be found as well. Occasionally, the maxillary nerve
indents the lower lateral wall as the nerve enters foramen rotundum. The pterygoid canal,
which carries the vidian nerve, can form a ridge across the sinus floor. In rare cases the
mandibular branch of the fifth cranial nerve leaves a groove across the inferior portion of
the sinus.
The sphenoid ostium is located approximately 1.5 cm above the sinus floor on the
anterior wall of the sinus and can be round but is more frequently oval shaped with the
long axis in a vertical plane. Dixon (8) found that the average diameter of a round ostium
is roughly 3 mm, whereas oval ostia average 2.4 by 4 mm. Because of its position above
the sinus floor, drainage out of the sphenoid sinus is reliant on mucociliary flow to lift
debris against gravity to the ostium. Anecdotal reports suggest that inappropriately
inferior sphenoidotomies may result in mucous recirculation problems similar to those
seen in the maxillary sinus (9). However, the high location of the ostia does provide a
theoretic benefit in that it is tucked up out of the way of the nasal airflow, avoiding most
inhaled pathogens.
INFLAMMATORY DISEASE
In its healthy state, the sphenoid sinus is well ventilated through a patent ostia, mucus is
cleared by an active mucociliary mechanism, and local and systemic immunity prevent
growth of bacteria and fungus. However, disruption of any element in this delicate
balance can quickly lead to the opportunistic growth of microorganisms or the
accumulation of excessive mucoid debris within the sinus. Inflammatory diseases of the
sphenoid sinus occur in conjunction with the other paranasal sinuses (common) or may
occur in an isolated fashion (uncommon). It has been stated that perhaps the most reliable
feature of isolated sphenoid sinus disease is difficulty in its diagnosis (10). Most patients
present with headaches, usually retroorbital in nature. However, aside from headache,
there are essentially no other classically defining symptoms of disease within the
sphenoid sinus. Patients may present with any of a wide array of vague complaints,
including blurred vision, diplopia, hypoesthesia of the maxillary trigeminal nerve, and
dysfunction of other neighboring cranial nerves. Rarely do patients with disease limited
to the sphenoid sinus complain of nasal obstruction, and the incidence of purulent
rhinorrhea is highly variable.
Acute Bacterial Sphenoiditis
The overall incidence of acute bacterial sphenoiditis has decreased significantly with the
advent of antibiotics, although this trend may begin to reverse with the emergence of
increasing numbers of resistant bacteria. Multiple factors have been identified as possible
risk factors for the development of acute sphenoid sinusitis, including diving in
contaminated water, cocaine or steroid use, diabetes, and nasal fractures. With acute
bacterial sphenoiditis, patients tend to be clinically ill with fever, purulent rhinorrhea, and
elevated white blood cell counts, although a normal white blood cell count is by no
means satisfactory evidence against acute sphenoiditis. Bacteriology studies by Lew et al.
(11) demonstrated that for most patients, acute sphenoiditis is the result of gram-positive
infection, usually streptococcal or staphylococcal species. This is different from chronic
sphenoiditis, where cultured organisms tend to be evenly divided between gram-negative
and gram-positive species (11). Broad-spectrum antibiotics, often initially via an
intravenous route, are the treatment for acute bacterial sphenoiditis. In addition, an effort
should be made to maximize mucociliary function in the sphenoethmoidal recess with a
combination of mucolytics, decongestants, and saline irrigations (Fig. 34.4). For patients
who are clinically ill, fail to respond to medical therapy, or show evidence of
complication resulting from spread of infection to neighboring structures, consideration
must be given to decompression of the sphenoid sinus. This may be accomplished via an
endoscopic or an open approach, based on the individual patient characteristics and the
preference of the surgeon.

FIGURE 34.4. Computed tomography of acute sphenoid
sinusitis before (A) and after (B) medical therapy.



Complications resulting from acute sphenoiditis include orbital cellulitis and abscess,
hypopituitarism, sepsis, subdural and epidural abscess, cavernous sinus thrombosis,
meningitis, intracranial abscess, cerebral infarction, and blindness.
Invasive Fungal Sinusitis
Invasive fungal sinusitis is a rare but potentially devastating subset of sinonasal disease
that may involve the sphenoid sinus in immunocompromised patients. However, invasive
fungal sinusitis is rarely encountered isolated to the sphenoid sinus; it typically involves
multiple paranasal sinuses. Invasive fungal infections are most commonly seen in patients
with uncontrolled diabetes mellitus, usually during an episode of diabetic ketoacidosis.
Fungi favoring high-glucose acidic environments include Mucor, Rhizopus, and Absidia.
Neutropenic patients are more susceptible to infection from Aspergillus species.
Diagnosis can be difficult in the early stage of disease and requires a high degree of
suspicion in patients at risk to avoid tragic complications from intracranial spread of
infection along the multiple vascular pathways surrounding the sphenoid sinus. Any
immunocompromised patient with fever, purulent rhinorrhea, facial pain, headache, or
erythema deserves evaluation. Nasal swabs and visualization via endoscopic techniques
can be helpful, but the diagnosis relies on a nasal mucosal biopsy directed toward
identifying fungal elements. Therapy is geared toward reversing the underlying
immunologic insult, excision of all necrotic tissues, and treatment with appropriate
antifungal medications.
Allergic Fungal Sinusitis
Over the past two decades, a separate form of fungal sinusitis has emerged. Allergic
fungal sinusitis (AFS) differs from invasive fungal sinusitis in several key features. AFS
typically presents with polyposis and pansinusitis (including the sphenoid). Afflicted
sinuses are filled with a material referred to as allergic mucin (Fig. 34.5), which is
characterized histologically as eosinophil-laden mucin mixed with Charcot-Leyden
crystals and noninvasive fungal forms. Because of the fundamental lack of tissue
invasion by these fungi, the vascular compromise and frank necrosis of tissue, which is
characteristic of invasive fungal sinusitis, is not observed in AFS. However, AFS is
capable of significant bony erosion and sinus expansion (12). This is frequently noted on
CT, in addition to hypercalcified mucus (Fig. 34.6.)

FIGURE 34.5. Allergic fungal mucin as encountered
endoscopically.



FIGURE 34.6. Allergic fungal sinusitis seen eroding
through the anterior cranial fossa (A) and posteriorly
through the clivus (B).



Although Aspergillus was initially implicated as a primary organism, more recently the
role of dermatiaceous fungi, such as Bipolaris, Curvularia, Alternaria, and
Cladosporium, has been elucidated. The pathophysiology of this disease remains a point
of debate, but data increasingly point toward an allergic rather than infectious etiology,
similar to that seen in brochopulmonary fungal disease. Traditional forms of treatment for
AFS have included adjunctive topical and systemic steroids, endoscopic extirpation, and
systemic and topical antifungal medications. Regardless, recurrence rates have been
unsatisfying, leading to interest in newer forms of therapy.
Over the past decade, a new therapeutic approach to AFS, based on the immunologic
aspects of the disease, is beginning to emerge. Recognizing the role of allergic
hypersensitivity in the pathophysiology of AFS, the disease is treated in a fashion similar
to the way that inhalant allergies are treated. First, the patient's exposure to fungal antigen
is reduced by surgical extirpation of fungal mucin. Care is taken to adhere to the
principles behind endoscopic surgery; only tissue that is obstructing or diseased is
removed, whereas all other tissue is preserved. Next, perioperative use of systemic
corticosteroids, nasal saline irrigations, and dbridement of nasal crusts (as indicated)
helps to assist the healing process and inhibit the early accumulation of fungal debris.
After surgical eradication of most allergic mucin, immunotherapy with fungal antigens
can be initiated without fear of exacerbating a Gell and Coombs type III reaction
(immune complex formation). This protocol has significantly diminished the need for
long-term corticosteroids and decreased the recurrence rate of this frustrating disease
(13).
Mycetomas
Mycetomas, or fungal balls, are another form of fungal disease that affects the sphenoid
sinus. A mycetoma is a ball or nest of fungal elements that grows within the moist warm
sinonasal environment (Fig. 34.7). Fungal balls usually mimic chronic sphenoiditis in
presentation, although they can be asymptomatic for extended periods of time. Although
a wide variety of fungal subtypes have been known to create mycetomas, as a general
rule they occur despite adequate host immunity and are noninvasive. However,
depending on the involved fungi, these infections carry a theoretic risk of converting to
invasive fungal sinusitis if host immunity diminishes.

FIGURE 34.7. Isolated sphenoethmoid mycetoma
(fungal ball).



Chronic Sphenoiditis
In addition to fungal balls and AFS, the sphenoid sinus is subject to other chronic
inflammatory disorders. Chronic bacterial sphenoid sinusitis, often in conjunction with
other paranasal sinuses, may result from obstructive polyposis of the sphenoethmoid
recess. Obstruction of the sphenoethmoid recess disrupts the normal mucociliary outflow
tract, resulting in a self-perpetuating cycle of obstruction, mucin stasis, and chronic
bacterial infection. Patients with chronic sphenoid sinusitis typically present with a long
history of purulent nasal discharge, postnasal drainage, and headaches. Evaluation of the
paranasal sinuses with CT reveals thickening of the lining mucosa and sinus
opacification. Therapy of chronic sphenoid sinusitis, as in chronic sinusitis of all
paranasal sinuses, should be geared toward removal of the obstructing polyps and debris
to return the sinus to its healthy state of effective mucociliary clearance. This is usually
best done through regular saline irrigations, use of nasal steroids, and an extended course
of antibiotics. Those patients who fail to respond to medical management should be
considered for surgical therapy.
Mucoceles
Like other paranasal sinuses, mucosa within the sphenoid sinus can form a mucocele
either as a result of expansion of a mucus retention cyst (primary mucocele) or an
obstructed sphenoid ostium (secondary mucocele). Despite being quite rare, mucoceles
are probably the most common isolated lesions found in the sphenoid sinus after sinusitis
(14,15). Mucoceles are usually clinically silent for years, but as they progressively
enlarge, they begin to exert pressure on surrounding structures and ultimately can result
in resorption of surrounding bone (Fig. 34.8). Ultimately, this process leads to
symptomatic involvement of structures surrounding the sphenoid sinus. Thus, although
these are inflammatory lesions by definition, their clinical course can mimic tumors of
the sellar-parasellar region in presentation. Suspected patients should undergo evaluation
with CT to delineate areas of bony destruction and the extent of disease. Confirmation is
commonly done with magnetic resonance imaging (MRI). With complete obstruction of
the sphenoid sinus, water is progressively reabsorbed from the mucocele, leaving behind
increasing concentrations of protein. When the protein concentration within a mucocele
reaches 25% to 30%, MRI reveals T1 hyperintensity with relatively hypointensity on T2
images (16). Treatment of these patients requires creation of a wide sphenoidotomy with
decompression of the mucocele. This can generally be accomplished with an endoscopic
approach, although extensive disease may require more aggressive open procedures.

FIGURE 34.8. Right sphenoid mucocele eroding through
the skull base. Note the absence of bone along the clivus
and sphenoid sinus roof.



NEOPLASTIC DISEASE
If isolated inflammatory disease of the sphenoid sinus is a relative clinical rarity, then
primary tumors of the sphenoid are an exceedingly rare phenomenon. That said, a wide
spectrum of neoplasms has been documented throughout the literature as either arising
within or involving the sphenoid sinus (Table 34.2). Neoplasms that primarily arise
within the sphenoid sinus are almost always epithelial in origin. This includes benign
lesions such as papillomas and adenomas. These lesions are generally treated with
complete excision, although a wide local excision is probably indicated for inverting
papillomas because these lesions have a known propensity to harbor squamous cell
carcinoma.

TABLE 34.2. TUMORS OF THE SPHENOID BONE



Fibrous Dysplasia
Fibrous dysplasia occurs within the sphenoid sinus as an isolated lesion (17) but is more
frequently found involving the sphenoid sinus in conjunction with surrounding structures.
This is probably due to fibrous dysplasia's predilection for membranous bone, making it
rare within the precartilaginous bone of the sphenoid sinus (18). However, when this
disease does involve the sphenoid sinus, it poses a significant problem because of its
tendency to progressively replace normal bone with metastatic woven bone. On CT, it
appears as a mixture of lytic and sclerotic bone components with obliteration of involved
neuroforamina (16).
Chordoma
Chordomas typically arise from the clivus and extend by direct expansion into the
sphenoid sinus. These lesions derive from notochordal remnants and appear as gray,
gelatinous, multilobulated tumors. They are rarely metastatic but are commonly locally
aggressive and invasive. Both CT and MRI play a role in defining bony destruction and
brain involvement, whereas treatment usually involves surgical removal followed by
radiation therapy (19).
Malignant Tumors of the Sphenoid
Primary malignancies arising of the sphenoid sinus are very rare but are documented to
arise from a wide variety of tissue subtypes. Perhaps the most common tumors are
adenocarcinomas, chondrosarcomas, and lymphoepitheliomas. These tumors present with
the same symptoms as other sphenoid lesions: headaches, visual disturbance, and cranial
nerve dysfunction. However, their location deep within the sphenoid bone makes for a
difficult early diagnosis; thus, many tumors are metastatic or demonstrate advanced stage
at the time of diagnosis. More common than primary malignancy arising within the
sphenoid sinus is either direct invasion by neighboring malignancies or metastatic spread.
For example, meningiomas and tumors of the overlying sellar region are not
uncommonly found invading the sphenoid sinus.
OPERATIVE TECHNIQUES
Operative intervention of the sphenoid sinus involves a delicate balance of goals. On one
hand, the surgeon must achieve adequate exposure of the sphenoid sinus within a
confining confusing operative field to successfully achieve drainage procedures or tumor
resections. On the other hand, proximity of sensitive anatomic structures to the sphenoid
sinus often limit wide exposure. Misguided efforts to improve exposure can result in a
frightening array of operative complications. Therefore, each of the many operative
approaches to the sphenoid sinus should be viewed as a balance between exposure and
operative risk.
Open Approaches
In 1885, Schaffer was the first surgeon to document attempts at sphenoid sinus surgery,
making use of gouges and punches via a transnasal approach to open the anterior wall of
the sinus. Unfortunately, limited visibility led to a high rate of complications. As this
approach was refined through the work of Kocher, Hirsch, Halstead, and Cushing (20),
the incidence of operative complications began to fall.
Today, several techniques for open exposure of the sphenoid sinus remain in use.
Arguably, the most popular open approach is the transseptal approach, which can be
performed via a columellar incision or a sublabial incision (with or without a Le Fort I
osteotomy). Traditionally, there has been concern regarding increased morbidity with the
sublabial approach, citing complications such as lip numbness and oronasal fistulas.
However, Spencer et al. (21) compared the transcolumellar approach with the sublabial
approach and found virtually no difference in complication rates. Alternatives to the
transseptal approach include access to the sphenoid sinus through the ethmoid air cells
(either as a transmaxillary approach or a transorbital approach) or via a transpalatal
approach.
All these techniques share several advantages: they provide wide exposure, they keep the
surgeon consistently oriented to the spatial relationships within the operative field, and
they provide binocular vision, which can be an added advantage in some situations.
However, the open techniques are more invasive than endoscopic procedures, and the
exposure provided is often unnecessarily excessive, especially for small tumors or
masses.
Endoscopic Approaches
Endoscopic approaches to the sphenoid sinus are gaining popularity, especially as
surgeons become more comfortable with endonasal anatomy. These techniques allow for
minimally invasive access to the sphenoid sinus and provide for more physiologic
sphenoid drainage. However, endoscopic approaches require surgical experience and skill
sufficient to identify key landmarks and maintain orientation within an operative field
that can be a confusing mix of polyps, blood, anatomic variations, and previous surgical
changes.
Traditionally, endoscopic localization of the sphenoid sinus has relied on presumed
distances and angles from the anterior nasal spine using direct measurements, commonly
with a calibrated suction (Fig. 34.9). As expected, the individual variability of this region
from patient to patient severely limits such methods. In an effort to standardize
endoscopic sphenoidotomy and prevent operative complications, Bolger et al. (22)
developed a technique to localize the sphenoid sinus based on a set of consistent
landmarks. Their technique relies on entering the superior meatus through the basal
lamella, allowing identification of the anteroinferior aspect of the superior turbinate.
Dissection then proceeds laterally to define the posterior limit of the lamina papyracea.
The resultant ethmoid cavity is referred to as the posterior ethmoid box. The medial limit
of this box consists of the lateral aspect of the superior turbinate; the lateral limit is the
lamina papyracea, with skull base defining the roof and the horizontal portion of the
superior turbinate (attaching to the lateral nasal wall) defining the floor. Once each of
these boundaries is defined, the anterior face of the sphenoid sinus can easily be
identified as the posterior wall of this box. Further, the natural ostium of the sphenoid
sinus can be reliably located by gently removing the inferior portion of the superior
turbinate. Care must be taken with this technique, because overaggressive mobilization of
the superior turbinate can lead to cerebrospinal fluid leaks and/or anosmia. Overall, this
technique provides the surgeon with a set of consistent landmarks for safe and rapid
localization of the sphenoid sinus and its ostium.

FIGURE 34.9. Fluoroscopic image of a calibrated
suction measuring the distance to the skull base.



CONCLUSIONS
Treatment of sphenoid sinus disease is best tailored to the individual needs of each
patient. In many cases, inflammatory sphenoid disease will respond to appropriate
medical therapy with rare need for surgical intervention. However, persistent
inflammatory disease that is nonresponsive to medical therapy, invasive fungal disease,
and neoplastic diseases tend to require surgical intervention. The method of surgical
intervention will be determined by patient factors and the preferences of the surgeon.
Extensive locally invasive disease processes may require more aggressive open
procedures, whereas limited diseases or focal lesions can best be addressed through
endoscopic approaches that minimize morbidity. Regardless, care of the sphenoid sinus
requires that the clinician understands both the development and anatomy of this complex
region. This is especially true when one considers the relative rarity of disease isolated
solely to the sphenoid sinus. Although often a focal point for disease, the sphenoid sinus
cannot be addressed without considering the effects on its neighboring structures and the
patient as a whole.

HIGHLIGHTS
The presenting symptoms of lesions within the sphenoid sinus
tend to be vague, with headache the only reliable finding.
Because of the anatomic proximity of the sphenoid sinus to
important optic and intracranial structures, acute sphenoid
sinusitis is considered a medical emergency.
Left untreated, sphenoid sinus disease can result in grave
complications, including cavernous sinus thrombosis, orbital
infections, hypopituitarism, sepsis, intracranial infections, and
blindness.
A variety of open techniques is used to access the sinus, often
with similar results.
Endoscopic approaches are acceptable alternatives, and the
superior turbinate offers a useful landmark for localization of
the sphenoid natural ostia.
CHAPTER REFERENCES
1. Alyea OE. Sphenoid sinus: anatomic study, with consideration of the clinical significance of the
structural characteristics of the sphenoid sinus. Arch Otolaryngol 1941;34:225253.
2. Cope VZ. Internal structure of the sphenoid sinus. J Anat Phys 1917;51:127132.
3. Elwany S, Yacout YM, Talaat M, et al. Surgical anatomy of the sphenoid sinus. J Laryngol Otol
1983;97:227241.
4. Levine H. The sphenoid sinus, the neglected sinus. Arch Otolaryngol 1978;104:585587.
5. Fuji K, Chambers SM, Rhonton AL. Neurovascular relationships of the sphenoid sinus: a
microsurgical study. J Neurosurg 1979;50:3139.
6. Waridel F, Monnier M, Agrifoglio A. Evaluation of the bone resistance of the sphenoid and
ethmoid sinuses. Laryngoscope 1997;107:16671670.
7. Bansberg SF, Harner SG, Forbes G. Relationship of the optic nerve to the paranasal sinuses as
shown by computed tomography. Otolaryngol Head Neck Surg 1987;96:331335.
8. Dixon FW. Catheterizing the sphenoid sinus. Arch Otolaryngol 1939;30:994.
9. Yanagisawa E, Weaver WM. Endoscopic view of the recirculation phenomenon of sphenoid sinus
drainage. Ear Nose Throat J 1996;75:6870.
10. Hnatuk LA, Macdonald RE, Papsin BC. Isolated sphenoid sinusitis: the Toronto Hospital for Sick
Children experience and review of the literature. J Otolaryngol 1994;23:3641.
11. Lew D, Southwick FS, Montgomery WM, et al. Sphenoid sinusitis: a review of 30 cases. N Engl J
Med 1983;19:11491154.
12. Nussenbaum B, Marple BF, Schwade ND. Characteristics of bony erosion in allergic fungal
sinusitis. Presented at the Meeting of The Southern Section of the American Laryngological,
Rhinological and Otological Society, St. Petersburg, FL, January 14, 2000.
13. Folker RJ, Marple BF, Mabry RL, et al. Treatment of allergic fungal sinusitis: a comparison trial
of postoperative immunotherapy with specific fungal antigens. Laryngoscope 1998;108:1623
1627.
14. Sethi DS. Isolated sphenoid lesions: diagnosis and management. Otolaryngol Head Neck Surg
1999;120:730736.
15. Lawson W, Reino AJ. Isolated sphenoid sinus disease: an analysis of 132 cases. Laryngoscope
1997;107:15901595.
16. Chong VFH, Fan YF, Tng CH. Pictorial review: radiology of the sphenoid bone. Clin Radiol
1998;53:882893.
17. Mladina R, Manojlovic S, Markov-Glavas D, et al. Imaging case of the month: isolated unilateral
fibrous dysplasia of the sphenoid sinus. Ann Otol Rhinol Laryngol 1999;108:11811183.
18. Brunner H. Fibrous dysplasia of the facial bones and paranasal sinuses. Arch Otolaryngol
1952;55:4354.
19. Isaacs RS, Donald PJ. Sphenoid and sellar tumors. Clin Otolaryngol 1995;6:11911229.
20. Ghorayeb BY. Sphenoidotomy. Head Neck 1987;9:244249.
21. Spencer WR, Levine JM, Couldwell WT, et al. Approaches to the sellar and parasellar region: a
retrospective comparison of the endonasal-transsphenoidal and sublabial-transsphenoidal
approaches. Otolaryngol Head Neck Surg 2000;122:367369.
22. Bolger WE, Keyes AS, Lanza DC. Use of the superior meatus and superior turbinate in the
endoscopic approach to the sphenoid sinus. Otolaryngol Head Neck Surg 1999;120:308313.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

35 COMPLICATIONS OF SINUS SURGERY
Head & Neck SurgeryOtolaryngology
35




COMPLICATIONS OF SINUS SURGERY
JAMES A. STANKIEWICZ

J.A. Stankiewicz: Department of Otolaryngology, Loyola University Medical Center, Maywood, Illinois.


Relevant Anatomy
Complications of Specific Procedures
Inferior Meatal Antrostomy
Middle Meatal Antrostomy
Frontal Sinus Surgery with Osteoplastic Flap
Intranasal Ethmoidectomy
Transantral Ethmoidectomy and External Ethmoidectomy
Sphenoidotomy
Caldwell-Luc Procedure
Orbital Complications
Orbital Hematoma
Blindness
Diplopia
Nasolacrimal Duct Injury
Subcutaneous Emphysema
Cerebrospinal Fluid Fistula
Hemorrhage
Synechia
Paresthesia and Hypesthesia
Olfactory Loss
Brain Injury and Major Vessel Injury
Abnormality of Facial Growth and Sinus Development
Chapter References
Although most surgery performed for relief of sinus disorders is uncomplicated,
complications can occur as with any surgical procedure. The problem with complications
resulting from sinus surgery is that the opportunity for truly catastrophic complications,
such as blindness, diplopia, cerebrospinal fluid (CSF) fistula with or without meningitis,
intracranial brain injury, and life-threatening hemorrhage from carotid artery injury, is
ever present, making sinus surgery one of the most dangerous surgical procedures in
otolaryngology. It is important to understand the nature of these complications to increase
awareness and prevention. This chapter reviews relevant anatomy, discusses the
complications of specific sinus procedures, and evaluates specific complications,
pathophysiologic mechanisms, and management.
Despite intense preparation and experience, complications of sinus surgery do occur.
Most of these complications are temporary and minor, and most patients do well. Major
complications often are catastrophic, but fortunately they are extremely rare. With early
recognition, many complications can be controlled and reversed. It is always necessary
for the surgeon to be aware, prepared, and alert when performing operations on the
paranasal sinuses.
RELEVANT ANATOMY
Certain facts about the anatomic features of the sinuses have to be understood to avoid
the danger areas that can be compromised during surgery. The lamina papyracea divides
the orbit from the nose and the paranasal sinuses. Finding the lamina papyracea is
essential to preventing orbital complications. The orbit and the paranasal sinuses are
intimately related on three sides. The lamina papyracea separates the orbit and its
contents from the ethmoidal sinus. The medial wall of the orbit is formed from anterior to
posterior by the frontal process of the maxilla, the lacrimal bone, the lamina papyracea of
the ethmoid, and the sphenoid bone anteriorly only to the optic nerve foramen. The
lacrimal sac rests in the lacrimal groove anteriorly. The anterior and posterior ethmoidal
foramina are located in the frontoethmoidal suture line with the associated vessels and
nerves. Congenital dehiscence sometimes is present in the medial and superior walls of
the orbit, occurring behind the trochlear fossa or supraorbital notch and the middle or
outer thirds of the lamina papyracea or over the ethmoidal cells posteriorly.
The periosteum of the orbit (periorbita) represents the only soft-tissue barrier between the
ethmoidal sinus and the orbital contents. The periorbita is tough and fibrous but can be
elevated easily except at the suture lines, where it passes through to fuse with the
periosteum on the opposite side. The globe of the eye occupies most of the space in the
anterior orbit. The posterior orbit is filled with muscle and loosely vascular areolar tissue
(orbital fat). The orbital septum is the reflection of the periorbita into the tarsal plates.
Separating the anterior and posterior eye chambers, the septum is tough and holds the
orbital contents in place. It also holds orbital effusions such as hemorrhage and infection
in the orbit, preventing these conditions from passing directly to the lids but allowing
increases in orbital pressure.
The blood supply to the retina comes from two sourcesthe choroid choriocapillaris
(outer half) and the central retinal artery and branches. The blood supply is protected by
various compensatory mechanisms so that retinal blood flow is maintained even if the
entire system is under stress. Abundant communicating vessels from all sinuses enter into
the orbital contents and both lids. The inferior ophthalmic vein, in particular, begins as a
venous network along the floor and medial wall of the orbit. It receives tributaries from
the lacrimal sac, eyelids, and muscles of the orbit. There is free flow between these
orbital veins and the ethmoidal sinus, the nasolacrimal duct, and the turbinates. The
arterial supply between the orbit and the ethmoidal sinus consists of the anterior and
posterior ethmoid arteries, which run from the orbit through a bony canal into the septum.
The lamina is curved and gives way superiorly to the supraorbital ethmoidal cells and
inferiorly to the maxillary sinus. It is important to define the lamina surgically when
working in the ethmoidal and maxillary sinuses to avoid entrance into the orbit and
compromise of the periorbita and vascular supply. It is appropriate to stay near the
superior part of the inferior turbinate when making a middle meatal antrostomy and not
opening the antrostomy any more anteriorly than the anterior end of the middle turbinate.
After the antrostomy is made, the lamina papyracea can be identified just laterally and
superiorly to it (1). The operation should not proceed laterally to the antrostomy, or the
orbit will be encountered. This finding of the lamina papyracea in relation to the
antrostomy is essential to locating the orbit.
The nasolacrimal duct is 3 to 6 mm from the natural antrostomy. The anterior ethmoidal
cells encroach on the nasolacrimal sac at the level of the middle turbinate and duct at the
level of the middle meatus in 86% of patients. The nasolacrimal duct ostium enters the
nose within 1 cm from the end of the inferior turbinate in the middle meatus. Inferior
antrostomy should not be placed more anteriorly than 1 cm. In operations on children,
indenting of the canine teeth in the inferior meatus should be sought and avoided. If
antrostomy is necessary, the antrum is opened posteriorly and inferiorly, not anteriorly.
An unobservant surgeon can injure the lacrimal sac or duct if the anatomic details are not
kept in mind.
The structures of the orbit viewed through an endoscope appear different on the right and
left sides (2,3). The actual right nasal and meatal structures lie visually straight back. On
the left, the ethmoid sinuses are actually more medial in location, especially anteriorly
and superiorly. Because of altered perception, a surgeon operating on the left side who
takes the same straight-back approach as on the right, especially during an endoscopic
procedure, contacts lamina papyracea and enters the orbit, particularly in the superior and
lateral orbit area (Fig. 35.1). It is important to stay in the medial aspect against the middle
turbinate.

FIGURE 35.1. Anatomic differences in left side of nasal
cavity that are relevant during endoscopic surgical
procedures. A: To a right-handed surgeon, apparent
anatomic relations on the left side. B: Actual anatomic
relations with orbit pushing into ethmoidal sinus
superiorly and laterally. MT, Middle turbinate; FE, fovea
ethmoidalis; LP, lamina papyracea; IT, inferior turbinate.



Measuring the anatomic structures is important to avoiding complications. The distance
from the nasal spine or nasal opening to the frontal recess is 6 cm, to the base of skull is 7
cm, and to the anterior wall of the sphenoid is 7 cm in adults of normal size. The
nasopharyngeal wall approximates the back wall of the sphenoidal sinus, usually to
within 1 cm. The choanal bridge (just above the choana and below anterior wall
sphenoid) is 7 cm. The basal lamella of the middle turbinate is 6 cm. In children, these
dimensions are variable, and the surgeon needs to exercise caution. However, one can
always find the distance to the sphenoid bone and the base of the skull by measuring the
distance to the choanal bridge just above the choana (Fig. 35.2).

FIGURE 35.2. Beaded probe measurements to various
areas of the nose from the nasal opening (nasal spine).
(From Stankiewicz J. Complication of endoscopic sinus
surgery. Otolaryngol Clin North Am 1989;22:749, with
permission.)



The ostium of the sphenoidal sinus lies adjacent to the septum about 1.5 cm above the
choanal bridge, or about one third of the way up from the choana to the base of the skull.
It is the anatomic key to the base of the skull. This important structure often is obstructed
by posterior ethmoidal disease. However, a probe placed onto the sphenoidal ostium
safely identifies the appropriate area for opening into the sphenoidal sinus. This ostium
can be approached in a position medial to the middle turbinate or approached laterally in
a plane between the superior inferior turbinate and just above the attachment of the
middle turbinate to the choanal bridge. The sphenoidal ostia are just medial to the lower
one third to one half of the superior turbinate. The anterior wall of the sphenoidal sinus is
in a line with the maxillary antrostomy. The anterior aspect of the sphenoid bone usually
is extremely thin. If resistance is felt, the bone should not be penetrated. The posterior
ethmoidal cells can be opened in a medial direction through the posterior middle
turbinate to allow visualization of the sphenoidal ostium, which safely identifies the
lateral aspect of the sphenoidal and posterior ethmoidal cells that can be penetrated.
The surgeon should be aware that the roof of the nose slopes downward toward the
posterior. The anteriorly high fovea ethmoidalis lowers and flattens posteriorly toward
the sphenoid bone; in the posterior aspect, the fovea is at the level of the cribriform plate.
The anterior ethmoidal artery can pierce the cribriform plate and even be intracranial as it
travels medially toward the septum. Kainz and Stammberger (4) stated that the bone at
this point is ten times thinner than in other areas of the cribriform plate and thus can be
easily violated. Surgeons need to beware of a low base of the skull or cribriform plate, as
found at computed tomography (CT).
Despite controversy about nasal dryness and crusting after removal of the middle
turbinate, it is clear that the middle turbinate is an important landmark. It separates the
cribriform plate from the fovea ethmoidalis; its anterior tip marks the limits of anterior
dissection of maxillary antrostomy; the basal lamella identifies the entrance into the
posterior ethmoidal sinuses; and the lower half of the middle turbinate and its insertion
into the choana help to identify the entrance into the sphenoidal sinus. These
characteristics and sinus protection, direction of airflow, and smell relations make the
middle turbinate a structure to preserve if at all possible. However, turbinates that are
mechanically obstructive, such as concha bullosa or those full of polyps, must be partially
or totally removed, depending on the disease (Table 35.1).

TABLE 35.1. SUMMARY OF IMPORTANT
ANATOMIC RELATIONS



COMPLICATIONS OF SPECIFIC PROCEDURES
Specific complications of sinus surgery are numerous. Several can be catastrophic
because of the proximity of the paranasal sinuses to the orbit and brain. All
otolaryngologists should be familiar with Mosher's writings from the early twentieth
century decrying intranasal ethmoidectomy as one of the quickest ways to kill a patient.
Most of the catastrophic complications are related to ethmoidectomy and frontal sinus
surgery. Table 35.2 lists the complications of sinus surgery. Kennedy et al. (5) and May
et al. (6) studied the complications of sinus surgery among large populations of patients.

TABLE 35.2. COMPLICATIONS SINUS
SURGERY



Inferior Meatal Antrostomy
Complications of intranasal antrostomy are profuse bleeding due to injury to the greater
palatine artery, synechiae, osteomyelitis, and tooth numbness, pain, or injury. Barfoed et
al. (7) stated that inferior meatal antrostomy can cause injury to the teeth of children
because of the proximity of the developing canines to the nasal wall of the maxillary
sinus. They recommended looking for the canine impression in the lateral nasal wall
before performing microsurgical antrostomy on children. Muntz and Lusk (8) used a
small-rasp biting forceps to make 92 nasoantral windows in 39 children. No
complications occurred, and there was minimal morbidity. There also were no permanent
injury to the teeth, no numbness, and no bleeding.
Sogg (9) reviewed the results of 174 antrostomies performed on 87 adult patients. The
operations were performed with local anesthesia and rat-tail rasps, Takahashi forceps,
and rongeurs. The antrostomies were 2 to 2.5 cm, and there were no complications.
Sogg's main concern was failure of the procedure to control sinus disease.
It appears that although complications related to development of the teeth, especially
among children, and occasional bleeding can occur during inferior antrostomy, the risk of
permanent injury is low if care is taken during the procedure. The most concern is for
effectiveness of the nasoantral window and prevention of recurrent disease.
Middle Meatal Antrostomy
The complications of middle meatal antrostomy are bleeding, blindness, facial pain,
numbness, nasolacrimal duct injury, and synechiae. Middle meatal antrostomy was
discouraged after work by Hilding (10) in 1943 showed maxillary sinus drainage was
located in the natural ostia and should not be violated. By 1971, Lavelle and Harrison
(11) claimed a 94% success rate in operations on 150 patients without complications.
Davis et al. (12) performed 310 middle meatotomies endoscopically with no serious
surgical complications. Epiphora developed in 1 patient and synechia in 20 patients.
Serdahl et al. (13) described the treatment of 8 patients with nasolacrimal injury during
middle meatal antrostomy. Heermann and Neves's (14) experience over 25 years with
2,500 ethmoidectomies and both middle and inferior antrostomy showed minimal serious
complications. A few anecdotal reports exist of temporary pain and numbness due to
endoscopic middle meatal antrostomy. These complications were most likely caused by
injury to the alveolar nerves lining the meatal wall of the maxillary sinus.
Stammberger and Posavetz (15) reviewed the records of 500 patients with functional
endoscopic sinus surgery and found an 8% incidence of synechiae. In reviewing the
records of more than 4,500 patients, Stammberger and Posavetz (15) found no instance of
blindness, permanent pain, bleeding, or numbness. In 300 antrostomies, Stankiewicz (16)
found two cases of epiphora. Middle meatal antrostomy is a relatively complication-free
procedure with sporadic reports of numbness and pain. Although blindness is possible, it
usually is associated with ethmoidectomy.
Frontal Sinus Surgery with Osteoplastic Flap
Osteoplastic frontal sinus surgery with or without fat obliteration is an extensive
procedure performed most frequently on patients with refractory chronic sinusitis or
mucocele. Bosley (17) reviewed the records of 100 patients and found that 15 patients
had postoperative headache, 7 had an incomplete obliteration, and 3 of 7 had recurrent
disease. Therefore headache can herald recurrent disease. No other complications such as
permanent numbness were discussed. Zonis (18) reviewed 100 osteoplastic operations on
the frontal sinus and found that the most common problem was persistent hypesthesia in
the distribution of the supraorbital nerve.
Montgomery (19) reviewed a series of 250 patients and found that 47 patients (18%) had
early complications. Abdominal wound complicationshematoma, seroma, or abscess
were related to the fat graft. Hematoma, seroma, or abscess also occurred in the frontal
wound. Osteoplastic flap incisions were made outside the frontal sinus with exposed dura
but no brain injury. Four dural exposures were found when the mucous membrane was
stripped. Five dural lacerations occurred, two of which had to be repaired. Other
complications included necrosis of the skin of the dorsum of the nose, anosmia,
temporary ptosis, and temporary dysfunction of the frontalis muscle. After 8 years, 6% of
208 patients had persistent postoperative pain, and 1% had persistent neuralgia. These
complications occurred most often with brow incisions, in which the supraorbital nerves
usually are incised, as opposed to coronal incisions, in which the supraorbital nerves
usually are preserved. Poor appearance of the incision scar occurred among fewer than
1% of patients. Six percent had depression or elevation of the osteoplastic flap. This
complication can be avoided with bevelling of bone cuts and meticulous closure, with a
drill hole and wiring if necessary. Only 6% of patients needed revision surgery (19).
Lawson and Reino (20) found that 10% of 102 patients with osteoplastic flap had
embossment of the frontal bone flap. Six of the 12 patients needed surgery for repair. The
best way to avoid this problem is to wire or manipulate the flap into position to prevent
movement. Hypesthesia and wound infection are the most common complications after
osteoplastic flap surgery. Postoperative pain persists among 6% of patients, and almost
7% have scarring or forehead abnormalities. Although exposure of dura does occur, CSF
leak, meningitis, or brain injury is unusual. After operations on 43 patients, Ulualp,
Carlson, and Toohill (21) found that 6 patient has decreased sensation and 1 had CSF
leak.
Intranasal Ethmoidectomy
Intranasal ethmoidectomy can be performed with a headlight, microscope, or endoscope.
It has been described by Mosher (22) as perhaps the most dangerous of all
otolaryngologic operations. Catastrophic complications such as blindness, permanent
diplopia, CSF fistula with meningitis, brain injury, and major vessel injuries are known.
Synechiae, orbital hematoma, subcutaneous emphysema, loss of smell, and hemorrhage
also can occur. Freedman and Kern (23) and Friedman and Katsantonis (24) reported
overall complication rates less than 4% for traditional ethmoidectomy in more than 1,000
ethmoidectomies. Freedman and Kern (23) analyzed factors that contributed to
complications and implicated repeated procedures, extensive disease, and loss of
landmarks. Friedman and Katsantonis (24) espouse ethmoid marsupialization;
ethmoidectomy is performed in conjunction with sphenoidotomy. In 1,163 procedures,
the overall complication rate was 3%. The most common complications were asthma
attack and hemorrhage. The rate of major complications was low; CSF fistula and
epistaxis were the most common. In 1,000 consecutive intranasal ethmoidectomies
reviewed by Freedman and Kern (23), the most common complications were hemorrhage
and orbital hematoma; the overall complication rate was 2.8%.
Lawson (25) reported the results of 1,077 intranasal ethmoidectomies over a 15-year
period. The overall complication rate was 1.1% but included three CSF fistulae. Included
in this review of ethmoidectomy was an extensive review of complications of all ethmoid
procedures. Complications of endoscopic sinus surgery mirror those of traditional
surgery. Stammberger and Posavetz (15), in a series of 4,500 cases, reported only six
major complications and no blindness, death, or double vision. Only three CSF fistulae
occurred. However, in a series of 500 of these patients who underwent close follow-up
evaluation, 8% had synechiae, and 15% of these patients needed revision procedures.
Surgery was aborted in 2% of patients because of hemorrhage. Other endoscopic
clinicians' results mirror the experience of Stammberger and Posavetz with minimal
major complications. Stankiewicz (16), however, reported a 17% complication rate in
150 ethmoidectomies and indicated that endoscopic ethmoidectomy is extremely difficult
for inexperienced surgeons. Stankiewicz also demonstrated in a second group of 150
ethmoidectomies a decrease in complication rate to less than 2%, indicating that with
experience endoscopic surgery is safe and that complication rates are at a level equivalent
to those of traditional ethmoidectomy and other endoscopic procedures. Stankiewicz
found that CSF fistula specifically and orbital complications in general are more
commonly among patients who are under general anesthesia for endoscopic
ethmoidectomy. No experienced surgeon claims to have had a patient with blindness or
double vision. Cerebrospinal fluid fistula with meningitis also is rare.
In more than 4,000 microscopic ethmoidectomies, Heermann and Neves (14) found no
vision loss, diplopia, or CSF fistula. One patient died of brain abscess and one of
meningitis from a lacrimal sac infection. No mention was made of any other
complications. May et al. (6) found in a metaanalysis of 6,801 patients that the main
serious complication of ethmoidectomy was CSF rhinorrhea. Serious complications
occurred among almost 1% of patients. Orbital penetration was the most common minor
complication. Complication rates were similar for endoscopic and traditional techniques
except for a higher rate of orbital penetration in traditional surgery.
Intranasal ethmoidectomy in the hands of experienced surgeons has an overall
complication rate of 4% or less (6). However, when the middle turbinate is preserved,
complications due to synechiae are more apparent and the complication rate increases.
The complications include revision surgery due to middle turbinate synechiae. Factors
that make ethmoidectomy hazardous include general anesthesia; numerous previous
operations; advanced disease, particularly long-term chronic disease or fungal disease;
intraoperative hemorrhage; operations by a right-handed surgeon on the right side of the
head; endoscopic procedure by a right-handed surgeon on the left side of the head; and
inexperience of the surgeon.
Transantral Ethmoidectomy and External Ethmoidectomy
Complications of transantral ethmoidectomy and external ethmoidectomy are the same as
for intranasal ethmoidectomy. However, because direct vision with or without a
microscope is used, fewer major complications are found. Transantral ethmoidectomy
necessitates a Caldwell-Luc operation and can be difficult. It is also important that the
distance to the ethmoidal and sphenoidal sinuses through a transantral approach is half
that of an intranasal approach.
Because external ethmoidectomy produces an external scar, patients can expect some
deformity, especially if the incision is extended for frontoethmoidectomy. Kimmelman et
al. (26) reported on 47 external ethmoidectomies and found a 55% complication rate.
Most of the complications were minor orbital problems. Common complications were
periorbital edema (16%), supraorbital anesthesia (6%), hemorrhage (9%), and wound
infection (6%), all of which resolved. Lacrimal sac problems and forehead numbness can
be caused by injury to the supraorbital nerves. Almost all patients have ecchymosis from
an injury to the angular vessels and lid edema from the incision.
In 158 transantral ethmoidectomies on 98 patients, Malotte et al. (27) found increased
blood loss (average 384 mL) and an average hospitalization of 3.6 days. A total of 20.4%
of patients had complications. Complications such as intracerebral hemorrhage,
pneumocephalus, and CSF fistula occurred among 3.1% of patients. Minor complications
such as infraorbital nerve numbness, atrophic rhinitis, crusting, epistaxis, diplopia, and
epiphora also were found. Infraorbital nerve injury with numbness was the most common
complication. Friedman and Katsantonis (24) reported the results of 137 transantral
ethmoidectomies on 69 patients. They found two major complicationsCSF fistula and
hemorrhageand eight minor problems, seven with postoperative pain and numbness.
Kimmelman et al. (26) found a 42% rate of complications in 74 transantral procedures.
Temporary facial pain and edema occurred among 14% and 5% of patients, respectively.
Temporary molar and lip anesthesia occurred among 9% of patients. No major
complications were found.
Neal (28) found optic nerve injury, corneal abrasions, exposure keratitis, trochlear and
medial rectus injury, and diplopia from enophthalmos as potential orbital complications
from external ethmoidectomy. Cerebrospinal fluid fistula is possible and does occur. It
can be repaired directly because of the degree of exposure obtained with the external
approach. Neal mentioned the need for possible scar revision, especially if webbing of
the incision occurs. In 41 frontoethmoidectomies Dedo and Broberg (29) had no
complications and a 97% success rate.
Although complications occur frequently in transantral and external ethmoidectomy,
most are minor and resolve. Major complications are rare owing to the excellent exposure
afforded by these procedures but seem to be more common than with intranasal surgery.
It is important to reiterate that the distance to the sphenoidal sinus in an external or
transantral approach is about 4 cm. In the transnasal approach the distance is 7 cm.
Sphenoidotomy
Thirteen important structures are contiguous with the sphenoidal sinus. These structures
include the carotid artery, cavernous sinus, optic nerve, and the brain. Many of these
structures can be injured during sphenoidotomy, whether operation is external,
transantral, intranasal, or transseptal. These injuries are catastrophic but rare. Friedman
and Katsantonis (24) reported no complications related to sphenoidotomy in 1,168
intranasal sphenoethmoidectomies and 137 transantral procedures. Malotte et al. (27)
found no sphenoidotomy-related problems in 158 sphenoidotomies in conjunction with
transantral ethmoidectomy. The sphenoid wall in transantral sphenoidotomy is only 4 to 5
cm from the antral opening compared with 7 cm in transnasal sphenoidotomy.
Stankiewicz (30), in more than 400 endoscopic sphenoidotomy procedures, found one
CSF leak and no minor complications. Cerebrospinal fluid fistula can be repaired with a
number of intrasphenoidal techniques (see later). Vascular injury such as cavernous
sinuscarotid artery fistula or carotid artery injury is rare but can be fatal. Immediate
management can be successful (see later). Sphenoidotomy can cause major
complications, but these are rare.
Caldwell-Luc Procedure
Complications of the traditional Caldwell-Luc operation are facial swelling, cheek
discomfort, fever, hemorrhage, facial asymmetry, facial paresthesia, oroantral fistula,
gingivolabial fistula, dacryocystitis, devitalized teeth, recurrent polyps, and recurrent
sinusitis. The most common immediate complications are facial swelling and cheek
discomfort, which occur after almost 90% and 33% of procedures, respectively (31). The
most common long-term complications are recurrent sinusitis or polyps, facial
paresthesia, and dacryocystitis, which occurred among 12%, 5%, 9.1%, and 3% of
patients, respectively, in 670 Caldwell-Luc procedures (31). Yarington (32) reported on
271 Caldwell-Luc procedures with a 3% overall complication rate. The most common
complications were postoperative hypesthesia, devitalized teeth, and postoperative
ethmoiditis. Blindness can occur with the Caldwell-Luc procedure if the orbit is entered,
but this is a rare complication. Crockett et al. (33) reported on sinus surgery in the care of
40 children with cystic fibrosis and found initial pain and discomfort but no long-term
sequelae.
Major long-term complications of chronic pain and numbness are not as common as one
might believe (31,32). In a study by Yarington (32), because of modifications in
technique, no patient had long-term numbness and pain. The modifications included a
triangular flap in the buccal mucosa and the use of a drill rather than an osteotome,
mallet, and rongeur to open the anterior wall. DeFreitas and Lucente (31) found that
paresthesia, numbness, and other complications such as facial asymmetry, oroantral
fistula, dehiscence, and devitalized teeth persisted for about 1 year and then resolved or
necessitated minor surgical procedures. Murray (34) performed Caldwell-Luc procedures
on patients with chronic sinusitis. Numbness persisted among 8 of 45 patients for more
than 6 months. All patients had numbness and paresthesia, which resolved within 6
months except among the aforementioned 8 patients. Murray performed all the Caldwell-
Luc procedures in the traditional manner, in contrast to Yarington's modifications. Low
(35) reviewed 216 Caldwell-Luc operations and found that facial swelling, facial pain
and numbness, and dental pain and numbness were the most common complications
among 30% to 60% of patients.
The most common complications after Caldwell-Luc procedures are facial numbness,
paresthesia, and facial swelling. In most series, these complications resolve, but they can
persist among as many as 15% to 20% of patients. Modifications such as those mentioned
by Yarington (32) or Low (35) help to decrease these complications to a minimum. Table
35.3 summarizes the complications associated with sinus surgery.

TABLE 35.3. COMPLICATIONS BY
PROCEDURE



ORBITAL COMPLICATIONS
Orbital Hematoma
Orbital hematoma is caused by entrance through the lamina papyracea and can occur
whether or not the periorbita is injured. The risk of orbital hematoma with blood retention
in the retrobulbar space increases greatly with penetration of the periorbita. However,
ecchymosis can occur in either situation. Orbital hematoma is by definition a postseptal
injury. (The septum is defined as the fibrous membrane dividing the eyelid into anterior
and posterior chambers.) Orbital hemorrhage is caused most frequently by trauma to the
orbital veins lining the lamina papyracea and rarely by injury to the anterior and posterior
ethmoidal arteries. The difference between the two is the speed at which the clinical signs
and symptoms of retrobulbar hematoma develop. Hematoma from ethmoidal artery injury
occurs momentarily.
The difference between postseptal and preseptal (such as hematoma from injury to the
angular vessels with a needle injection) ecchymosis is that the preseptal hematoma is
darker and more diffuse and produces more lid edema. Postseptal hematoma, when
clinically significant, is marked by proptosis, conjunctival changes such as chemosis, and
pupillary changes, mydriasis, and a dilated pupil. Anisocoria (dilated pupil) can be
caused by topical or injected local anesthesia and is self-limited. Proptosis is not present,
and the eye is soft, unlike the situation with hematoma. Ecchymosis due to Caldwelll-Luc
external ethmoidectomy with a frontal osteoplastic flap usually is preseptal but can be
postseptal if the orbit is entered. Intranasal ethmoidectomy ecchymosis is postseptal.
Most cases of orbital hematoma do not have associated proptosis and pupillary changes,
but patients have to be observed closely so that these findings do not develop. These
findings signal increased orbital pressure and potential damage to the optic nerve. There
are two types of orbital hematomafast (arterial) hematoma and slow (venous)
hematoma (see later). Ecchymosis usually resolves in about 7 to 10 days. It progresses
from black and blue to yellow before disappearing.
Blindness
Blindness is a catastrophic complication of sinus surgery and can be temporary or
permanent. Temporary blindness is caused by orbital hematoma that has expanded to
such an extent that it increases orbital pressure, consequently compromising vascular
supply to the optic nerve, which is sensitive to ischemia. Studies with laboratory animals
have shown that increased intraocular pressure gradually returns to normal within 2 to 3
hours. However, light perception may not return for several more hours and the pupillary
reflex for 24 to 48 hours (36,37). In blindness caused by retrobulbar or retroorbital
venous hematoma, the retina can tolerate these extreme pressures perhaps for only 60 to
90 minutes. Intervention must take place within this time limit (36). In the case of fast
arterial hematoma usually due to anterior ethmoid artery injury and retraction into the
orbit, immediate high pressure on the optic nerve must be reduced in 15 to 30 minutes to
avoid blindness.
Even though compensatory mechanisms protect retinal blood flow, neural tissue is
vulnerable to ischemic injury. Even transient interruption of the blood supply can cause
neural tissue in the retina to become nonfunctional and unresponsive to light. Venous
outflow obstruction of the vessels supplying the optic nerve induces hypoxia. Prevention
of blindness begins preoperatively with a history and physical examination that exclude
potential problems (previous surgery, complicated surgery, or long-standing disease) and
patients who have bleeding problems or are taking medications such as aspirin that can
affect bleeding. Inquiries should be made regarding pathologic conditions of the eye that
can be related to blindness, such as glaucoma, amblyopia, diabetic retinopathy, and
retinal vascular disease. Scrutiny of radiologic studies, primarily CT scans, for evidence
of dehiscence or other problems is important.
Surgical planning commensurate with the ability and experience of the surgeon is
necessary. Operative prevention involves selection of appropriate anesthesia. General
anesthesia predisposes patients to a higher risk of orbital complication because orbital
pain is a sign that an anatomic barrier has been broached. Surgeons operating on the
ethmoid sinus should keep the eye uncovered and under constant scrutiny to notice
immediately any early proptosis, ecchymosis, or eye movement during the surgical
procedure. Although with an external procedure structures are apparent under direct
vision or binocularly, the use of an endoscope can distort anatomic features and
misrepresent depth of field, allowing entrance into the orbit. In rare instances, local
anesthetics or steroids injected in the area of the orbit can cause temporary or permanent
blindness.
In intranasal procedures, a right-handed surgeon is much more prone to cause injury on
the right side. During endoscopy a right-handed surgeon has to deal with anatomic
illusion on the left side. The superior lateral orbit is where the endoscopic approach to the
ethmoidal sinuses can lead to penetration and entrance into the orbit. The left ethmoidal
sinuses are actually more medial than appreciated by a right-handed surgeon (Fig. 35.1).
A technique helpful for endoscopic ethmoidectomy but also practical for microscopic or
traditional intranasal ethmoidectomy is the intraoperative bulb press test or simultaneous
eye palpation and intranasal examination (36,37) (Fig. 35.3). This simple maneuver
readily identifies movement of the periorbita or orbital contents and prevents entrance
into the orbit. This is also useful for identifying the lacrimal sac when removing agger
nasi cells. Identification of the maxillary sinus ostia and placement of the antrostomy
before proceeding with ethmoidectomy also help to identify the lamina papyracea early in
the procedure. Techniques such as having the nurse observe the eye for movement or
early ecchymosis can be helpful.

FIGURE 35.3. Bulb press test. A: Endoscope is in place
for examining meatus and lateral wall of the ethmoidal
sinus. A hole in the lamina papyracea is visible. B:
Simultaneous eye palpation and endoscopic palpation to
find periorbital or fat exposure as early as possible.
(Redrawn from Stankiewicz JA. Blindness and intranasal
endoscopic ethmoidectomy: prevention and management.
Otolaryngol Head Neck Surg 1989;101:320, with
permission.)



Tissues such as fat float in fluid, whereas others such as those encountered in sinus
disease and polypoid disease do not. The instrument nurse always should place fluid in
the specimen containers and should immediately inform the surgeon whether anything
floats. If orbital fat is found, it should be left alone and not tampered with. In most cases,
ecchymosis forms intraoperatively or postoperatively, and the patient should be watched
closely for orbital hematoma. The nose should not be overly packed. If a dehiscence is
present, the packing itself can press into the periorbita and posterior chamber, increase
pressure, and cause proptosis. Frontal sinus procedures, especially with obliteration, often
encounter the orbit from above. Orbital hematoma can occur with increased pressure if
orbital fat is present. Most eye swelling is otherwise preseptal.
Postoperative prevention revolves around informing the patient, nurse, and family about
what to expect and what to do if vision problems occur. Slow venous hematoma can
accumulate over 24 to 48 hours. Surgical outpatients need rigid guidelines for monitoring
and need inpatient observation if signs of orbital complications develop. When evidence
of orbital changes appears during any sinus-related procedure, especially ethmoidectomy,
immediate action must be taken. Blindness has been reported as a complication of all
forms of sinus surgery. Optic nerve injury is not reversible, but it is sometimes difficult to
separate the signs and symptoms of expanding retrobulbar hematoma, which can be
corrected, from those of optic nerve injury because in almost all cases there is evidence of
orbital hematoma.
A close working relationship between the ophthalmologist and the otolaryngologist is
needed to develop a treatment plan for patients with optic nerve injury. Table 35.4
outlines a protocol for management of these problems. Immediate eye massage to
redistribute orbital blood and decrease orbital pressure is begun (35,36 and 37) (Fig.
35.4). For delayed or slow orbital hematoma, mannitol should be started as an osmotic
diuretic at a dosage of 1 to 2 grams per kilogram of body weight in a 20% infusion. Use
of steroids is controversial in the treatment of patients with optic nerve injury due to
trauma. If glucocorticoids are used, the dosage should be high, such as 1 to 1.5 mg of
dexamethasone per kilogram of body weight divided over 24 hours. No information is
available on use of these agents to manage orbital hematoma, but there is anecdotal
evidence that glucocorticoids work well immediately.

TABLE 35.4. TREATMENT BLINDNESS
MANAGEMENT



FIGURE 35.4. Technique of orbital massage. A:
Appearance of retrobulbar hemorrhage after entrance into
lamina papyracea and injury to periorbita. B:
Redistribution of orbital hemorrhage by means of orbital
massage, which decreases orbital hemorrhage. (Redrawn
from Stankiewicz JA. Blindness and intranasal
endoscopic ethmoidectomy: prevention and management.
Otolaryngol Head Neck Surg 1989;101:320, with
permission.)



These medical measures usually lead to resolution of dangerous orbital pressure that can
jeopardize vision. However, close observation is necessary. If pressure is not reduced and
the eye is still under tension, and the patient is still without vision, surgical
decompression is necessary. Lateral canthotomy can be performed initially. Pressures can
be reduced dramatically and immediately. The wound usually heals well on its own and
does not require suturing. If pressure does not decrease, external medial orbital
decompression is necessary by means of Lynch external ethmoidectomy or endoscopic
decompression. If hemorrhage is from a lacerated anterior ethmoidal artery, the artery has
to be controlled, clipped, or cauterized. The lamina papyracea should be removed. If the
eye is still tense with increased pressure, the periorbita should be incised. The optic nerve
should be decompressed as a last resort, if expertise is available. Close observation of
vision is necessary postoperatively. Eye drops and diuretics are continued or used at the
discretion of the ophthalmologist.
Diplopia
Double vision is caused by injury to the ocular muscles most closely related to the
sinusesthe medial rectus and the superior oblique (2). The medial rectus is just lateral
to the periorbita at approximately the center of the lamina papyracea. The superior
oblique muscle is high in the orbit just lateral to the ethmoidal roof and anatomically is
much more difficult to reach intranasally. However, external ethmoidectomy can cause
injury if the periorbita is violated high in the orbit. The injury can be caused by direct
muscle injury or injury to the nervous or vascular supply to the eye muscle. Indirect
injury theoretically can occur as a result of heat conduction from a cautery or laser
through a dehiscence in the lamina papyracea. No published reports of this type of injury
are known. Unintentional injection of local anesthesia into the orbit can traumatize the
medial rectus muscle and cause temporary diplopia or anisocoria. Persistent diplopia
necessitates ophthalmologic evaluation and possibly surgery, which has a poor prognosis
(38). This is a rare complication.
Nasolacrimal Duct Injury
The lacrimal gland and sac are contiguous with the ethmoidal sinuses in almost 90% of
patients. The agger nasi cells are adjacent to the lacrimal sac, whereas the ethmoidal sinus
and natural antrostomy are associated with the lacrimal duct. To reiterate, the natural
antrostomy lies only 3 to 6 mm from the nasolacrimal duct, and the ostium opens into the
inferior meatus within 1 cm of the anterior end of the inferior turbinate. As a rule, the
ethmoidal sinuses or the natural antrostomy should not be opened anterior to the anterior
end of the middle turbinate or into the hardened bone separating the antrostomy from the
nasolacrimal duct. Inferior antrostomy is 1 cm or more behind the anterior inferior
turbinate in the inferior meatus.
Patients should be observed initially because most cases of epiphora resolve. However,
early epiphora is associated with permanent injury to the nasolacrimal system (13,39).
Both intranasal and external ethmoidectomy and inferior middle meatal antrostomy are
associated with this complication. Dacryocystitis can be associated with the Caldwell-
Luc procedure as well. If recovery does not occur, dacryocystorhinostomy may be
necessary to repair the injury. This repair can be accomplished intranasally,
microscopically, endoscopically, or externally (13,14,40).
Subcutaneous Emphysema
When a fracture or perforation occurs in the lamina papyracea during external or
intranasal ethmoidectomy, subcutaneous emphysema can occur (2,16). This complication
usually is caused by mask anesthesia and too vigorous bagging while the patient is
awakened, coughing, blowing the nose, vomiting, or straining, which allows air to enter
the soft tissue surrounding the eye. Observation for orbital hematoma is necessary,
especially if the periorbita has been violated. In rare instances subcutaneous emphysema
is considerable, even extending into the mediastinum. Treatment in most cases is simple
observation and reassurance. The emphysema usually reabsorbs within 7 to 10 days, but
some puffiness can persist for a few months (2,16).
CEREBROSPINAL FLUID FISTULA
Cerebrospinal fluid fistula occurs with all techniques of ethmoidectomy, frontal sinus
osteoplastic obliteration, and, in rare instances, sphenoidotomy. During ethmoidectomy
the dura can be entered anywhere from the anterior ethmoidal sinus to the sphenoidal
sinus. The changes in anatomic configuration make certain areas more susceptible (see
earlier). In the anterior aspect the cribriform plate is lower than the fovea ethmoidalis. It
is important that the surgeon stay away from the middle turbinate and operate laterally.
The slope of the base of the skull angles downward and becomes more horizontal as the
posterior base of the skull is approached. The base of the skull or cribriform plate can be
lower than usual (visualized on CT scans), increasing the risk of CSF fistula and brain
injury. The medial part of the roof of the base of the skull associated with the medial
portion of the anterior ethmoidal artery is almost ten times thinner than the rest of the
bone and can be easily penetrated (4). The dura is tightly attached, and the base of the
skull usually tears if bone is removed. The bone of the base of the skull is hard laterally
and not easily penetrated above the sphenoidal sinus. In the sphenoidal sinus, removing
disease from the superior wall or roof can cause a CSF fistula. Most reported fistulae
have occurred with the patient under general anesthesia. Some clinicians believe that
general anesthesia eliminates pain sensation in the base of the skull as a warning sign.
Endoscopic surgery is especially dangerous because of mononuclear vision and loss of
depth of field.
Cerebrospinal fluid fistula during frontal sinus obliteration usually occurs when the bone
incision is made outside the frontal sinus. Although a template is made to help delineate
the bone cut, occasionally the cut is too wide. Usually only dura exposure is found, but a
fistula may be present.
Cerebrospinal fluid fistula as a result of ethmoidal or sphenoidal surgery can be repaired
transantrally, externally, or intranasally during the operation if the leak is found
intraoperatively. Almost any type of living tissue membrane can be used to patch a
fistula; examples are fascia temporalis, septal or turbinate mucosa, and fascia lata (41,42
and 43). Local flaps of septal mucosa or middle turbinate also are successful. An
endoscope or microscope provides excellent intranasal visualization. Hemostasis is
absolutely necessary, and sometimes partial middle turbinectomy is performed for
exposure. Cerebrospinal fluid fistula in the frontal sinus is patched directly during the
operation.
Delayed fistula identification and location are important. Computed tomography with a
contrast agent helps to localize an active leak. Diluted fluorescein injected intrathecally
can be located with an endoscope after 20 to 30 minutes to help locate a CSF fistula
(41,42). Endoscopic examination alone may suffice to localize a CSF fistula. Delayed
fistulae can be repaired similarly to acute fistulae. Adjunctive help from a neurologist
with a lumbar tap or drain can be beneficial along with the mandatory bed rest. If an
attempt at external or intranasal closure is unsuccessful (repeated attempts can be made),
craniotomy is necessary. Use of antibiotics is controversial and should be used with
caution so as not to select out resistant organisms. Conservative management often
allows a CSF fistula to heal without surgery. Any leaks persisting for 2 to 3 weeks should
be closed surgically. Sphenoid CSF fistulae are more difficult to close externally because
of exposure but are visualized well endoscopically. Fibrin glue injected into the
sphenoidal sinus with or without a tissue graft may be successful.
HEMORRHAGE
Hemorrhage is one of the most common complications during or after sinus surgery.
Transantral or external procedures have more bleeding associated with them than do
intranasal procedures, although occasionally intranasal ethmoidectomy bleeding can be
profuse. Hemostasis for intranasal surgery has to be controlled before the operation
begins. Appropriate sedation, blood pressure control, anesthesia, administration of topical
and injectable anesthetics, vasoconstriction, and waiting time before the operation is
begun are important to decreasing risk of intraoperative hemorrhage (44,45).
Preoperative sedation and vasoconstriction with a topical spray in the surgical preparation
area improve blood pressure control and decongestion and diminish any systematic
reaction to topical cocaine. Cocaine is still the best topical vasoconstrictor and anesthetic
solution but should be used with caution in operations on patients with cardiac problems
and on children. For older patients, general anesthetic helps to control blood pressure
better than does local anesthesia, especially if the patient has asthma. Among patients
with asthma, medications used to lower elevated pressures can cause bronchoconstriction.
Severe asthma is much better controlled under general anesthesia. Such patients need to
be evaluated and anesthesia has to be tailored to the problem.
Only diseased tissue should be removed rather than widespread mucosal sacrifice (2,16).
Although bleeding from the ethmoidal artery usually is not a problem, the posterior septal
artery running below the sphenoid bone and feeding into the posterior middle turbinate
can cause marked intraoperative and postoperative hemorrhage. Prophylactic
cauterization of this artery may be helpful. Unipolar and bipolar endoscopic or
microscopic cauterization provides good control of this vessel (2,16). If turbinates are
removed, the remnant also should be prophylactically cauterized. Cauterization can be
painful to patients under local anesthesia. Local standby anesthesia with propofol,
ketamine, and midazolam allows excellent bleeding control in addition to cauterization.
Topical sprays such as tetracaine hydrochloridelidocaine with epinephrine or ephedrine
administered intraoperatively can help to control hemorrhage and pain. Visualization is
essential (2,16).
If bleeding is too great for intranasal surgery, especially endoscopic surgery, the
procedure should be terminated on that side or altogether. Often it is safer to come back
another day when bleeding usually is much less of a problem. Packing is placed at the
end of the operation if oozing continues. Use of polyvinyl acetal sponge or perforated
film absorbent dressing causes much less patient discomfort than does a nose full of
petrolatum gauze or iodoform, and both materials are easily removed.
SYNECHIA
The most common complication of endoscopic sinus surgery is synechia formation.
Synechia is especially common in functional or limited endoscopic sinus surgery with
preservation of the middle turbinate. Prevention of synechia involves meticulous surgical
technique with minimal manipulation of the middle turbinate and compulsive
postoperative care. Even so, the slightest abraded surfaces can form synechiae. Most of
these slight synechiae are not troublesome. Stammberger and Posavetz (15) reported that
8% of their patients had synechiae, and 15% of those needed revision. If the sinus
drainage area and middle turbinates are obstructed by a deviated septum, septoplasty
should be performed. The presence of a large symptomatic concha bullosa or polypoid
middle turbinate necessitates reduction.
Severely polypoid or atrophic middle turbinates are part of the disease and often must be
partially removed. Spacers are helpful to separate the middle turbinate from the lateral
wall. The ideal spacer is not yet available, but perforated film absorbent dressing works
well and is fairly nonreactive. Polyvinyl acetal sponge is satisfactory for a few days, but
tissue reaction and granulation occur if the material is left in place for a prolonged period.
Other spacers are anchored in the antrostomy to hold the middle turbinate in a medial
position or are actually fit on the turbinate.
Many surgeons routinely amputate the anterior end of the middle turbinate and find this
avoids synechia without sequelae. It is important to understand that any reduction or
undermining of the middle turbinate can predispose it to weakness, giving it a natural
tendency to lateralize, blocking the anterior or posterior ethmoidal sinus, frontal recess,
or antrostomy and precipitating infection. Patients with turbinate reduction have to be
observed for any evidence of lateralization. Removal of the agger nasi cells, if present,
often opens the meatus, dramatically reducing the chances of middle turbinate
lateralization. Middle turbinates can be attached to the septum by means of light scoring
of opposing tissue to set up a scar adhesion, which can be divided after ethmoidal healing
has occurred.
An antistaphylococcal antibiotic is used to prevent toxic shock syndrome, which can
occur in an acute or delayed manner owing to the presence of packing or retained crust.
Gelatin foam sheets, folded polymeric silicone, or hyaluronic acid gel packing can be
helpful in operations on children. It is important for any foreign material to be
appropriately anchored to avoid aspiration. Children may need follow-up examination
under anesthesia for dbridement of the nose, to take down synechia, and to make sure
the ostium and ethmoid remain open (43).
PARESTHESIA AND HYPESTHESIA
Paresthesia and hypesthesia are two of the most common complications of the Caldwell-
Luc procedure, external ethmoidectomy, and frontal sinus surgery (19,31,32,35). For the
most part, these are temporary complications that resolve 3 to 6 months after surgery.
Obvious nerve severance as in frontal sinus obliteration causes permanent numbness. A
small percentage of patients who undergo Caldwell-Luc procedures continue to have
permanent numbness or paresthesia. This can signal recurrent sinusitis or dental injury,
and medical treatment or revision surgery is needed to alter this problem if it is persistent.
Medical therapy includes antibiotics, systemic and injected steroids, and medications
such as phenytoin or carbamazepine to avoid neurologic problems. Yarington's (32) and
Low's (35) modifications to avoid these complications are discussed earlier.
OLFACTORY LOSS
There have been increasing injuries to the olfactory pathways after intranasal sinus
surgery (47). Jafek et al. (47) categorized injury to olfaction into three types
interference with access of oderant to olfactory nerve; damage to the olfactory nerve; and
damage to the central olfactory pathway. The emphasis must be on prevention of
olfactory injury.
BRAIN INJURY AND MAJOR VESSEL INJURY
Injury to the brain and major blood vessels is rare during sinus surgery. The anterior
communicating artery and its feeding vessels can be injured through the cribriform plate.
These vessels are surprisingly close once the cribriform is penetrated. They can also go
into spasm, resulting in serious central nervous system injury and sometimes death.
Frontal lobe syndrome with loss of memory, forgetfulness, and behavioral change also
can be caused by entrance through the roof of the nose into the brain. Sphenoidal surgery
and injury to the carotid artery can occur (48,49). The carotid artery can be dehiscent in
as many as 20% of sphenoidal sinuses. Carotid cavernous sinus fistulae also can occur.
Prevention of brain and vessel injuries necessitates that the surgeon be aware of anatomic
details, especially during operations on patients with structures compromised by disease
or previous surgery. If appropriate visualization is impossible because of bleeding, the
operation should be terminated. Sometimes radiologic evaluation in the operating room
with a cross-table lateral radiograph, fluoroscopy, or computerized stereotaxis can help to
establish the precise location of the nasal roof, base of the skull, and sphenoidal sinus.
Marked hemorrhage while during superior or posterosuperior approaches can herald
entrance through the nasal roof and brain injury.
All these conditions necessitate neurologic surgical intervention (48,49). Slight injury to
the brain can be managed quickly and with minimal deficit. Serious injury is always life-
threatening. Most patients who survive have a disruption of olfactory fibers with loss of
smell and can have persistent neurologic sequelae. The more quickly intervention takes
place, the better the chances for a good outcome. These types of injuries occur much less
frequently under local anesthesia. Neurologic changes with general anesthesia are not
found until the patient is awakened and even then can be delayed until the patient is wide
awake. In the case of carotid artery injury, action needs to be taken immediately (48,50).
A carotid drill should be established to aid in management of this problem (Table 35.5).
It is possible that with quick action a life can be saved (50,51).

TABLE 35.5. TREATMENT CAROTID DRILL



ABNORMALITY OF FACIAL GROWTH AND SINUS
DEVELOPMENT
Although growth disturbance and retarded sinus development have occurred in animals,
no clinical study has shown growth problems (46).

HIGHLIGHTS
There are no easy sinus operations.
Practical knowledge of anatomy is most important in avoiding
complications.
The lamina papyracea and middle turbinate should be identified
early in intranasal surgical procedures on the ethmoidal sinus.
Knowledge of distance relations aids in finding important
intranasal structures.
All sinus procedures have common minor complications that
resolve in most cases.
Major complications in sinus surgery are rare; however, when
they occur they often are catastrophic.
The complications of paresthesia and hypesthesia from the
Caldwell-Luc procedure can be avoided with alterations in
technique.
Distances to important structures in transantral
sphenoethmoidectomy are less than they are intranasal
procedures.
Blindness related to retroorbital hematoma can be reversed or
prevented if managed immediately.
Cerebrospinal fluid fistula can occur with almost any surgical
procedure on the sinuses and can be corrected during the
operation.
Operative or postoperative hemorrhage, especially during or
after intranasal surgery, can be prevented if a judicious
combination of anesthesia and surgery is used.
Intracranial or major vascular injury, if managed immediately,
can be minimized in some cases.
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15. Stammberger H, Posavetz W. Functional endoscopic sinus surgery. Arch Otorhinolaryngol
1990;247:63.
16. Stankiewicz J. Complications in endoscopic intranasal ethmoidectomy: an update. Laryngoscope
1989;99:686.
17. Bosley W. Osteoplastic obliteration of the frontal sinuses: a review of 100 patients. Laryngoscope
1972;82:1463.
18. Zonis R. Frontal sinus disease: 100 cases treated by osteoplastic operation. Laryngoscope
1966;76:1816.
19. Montgomery W. Surgery of the frontal sinus. In: Surgery of the upper respiratory system, 2nd ed.
Vol 1. Philadelphia: Lea & Febiger, 1979:162.
20. Lawson W, Reino AJ. Management of embossment following the frontal osteoplastic operation.
Laryngoscope 1996;106:1259.
21. Ulualp SO, Carlson TK, Toohill RJ. Osteoplastic flap versus modified endoscopic Lothrop
procedure in patient with frontal sinus disease. Am J Rhinology 2000;14:21.
22. Mosher H. The surgical anatomy of the ethmoid labyrinth. Ann Otol Rhinol Laryngol
1929;38:869.
23. Freedman H, Kern E. Complication of intranasal ethmoidectomy: a review of 1000 consecutive
operations. Laryngoscope 1979;89:421.
24. Friedman W, Katsantonis G. Intranasal and transnasal ethmoidectomy: a 20 year experience.
Laryngoscope 1990;100:343.
25. Lawson W. The intranasal ethmoidectomy. Laryngoscope 1994;104[Suppl]:49.
26. Kimmelman C, Weisman R, Osguthorpe J, et al. The efficacy and safety of transantral
ethmoidectomy. Laryngoscope 1988;98:1178.
27. Malotte M, Pett G, Chonkich G, et al. Transantral sphenoethmoidectomy: a procedure for the
1990's? Otolaryngol Head Neck Surg 1991;104:358.
28. Neal G. External ethmoidectomy. Otolaryngol Clin North Am 1985;18:55.
29. Dedo HH, Broberg TG, Nurr AH. Frontoethmoidectomy with Sewall-Boyden reconstruction: alive
and well, a 25 year experience. Am J Rhinology 1998;12:191.
30. Stankiewicz J. The endoscopic approach to the sphenoid sinus. Laryngoscope 1989;99:218.
31. DeFreitas J, Lucente F. The Caldwell-Luc procedure: institutional review of 620 cases: 1975
1985. Laryngoscope 1988;98:1299.
32. Yarington C. The Caldwell-Luc operation revisited. Ann Otol Rhinol Laryngol 1984;93:380.
33. Crockett D, McGill T, Healy J, et al. Surgery in children with cystic fibrosis. Ann Otol Rhinol
Laryngol 1987;96:367.
34. Murray J. Complications after treatment of chronic maxillary sinus disease with Caldwell-Luc
procedure. Laryngoscope 1983;93:282.
35. Low WK. Complications of the Caldwell-Luc operation and how to avoid them. Aust N Z J Surg
1995;65:582.
36. Stankiewicz JA. Blindness and intranasal endoscopic ethmoidectomy: prevention and
management. Otolaryngol Head Neck Surg 1989;101:320.
37. Stankiewicz JA, Chow JM. The two faces of orbital hematoma in endoscopic sinus surgery.
Otolaryngol Head Neck Surg 1999;120:841.
38. Penne RB, Flanagan JC, Stefanyszyn MA, et al. Ocular motility disorders secondary to sinus
surgery. Ophthal Plast Reconstr Surg 1993;9:53.
39. Bolger WE, Parsons DS, Mair SA, et al. Lacrimal drainage system injury in FEES: incidence,
analysis, and prevention. Arch Otolaryngol Head Neck Surg 1992;118:1179.
40. Metson R. Endoscopic surgery for lacrimal obstruction. Otolaryngol Head Neck Surg
1991;104:473.
41. Stankiewicz J. Cerebrospinal fluid fistula and endoscopic sinus surgery. Laryngoscope
1991;101:250.
42. Lanza DC, O'Brien DA, Kennedy DW. Endoscopic repair cerebrospinal fluid fistula and
encephaloceles. Laryngoscope 1996;106:1119.
43. Burns JA, Dodson EE, Gross CW. Transnasal repair of cranionasal fistulae: a refined technique
with long term follow up. Laryngoscope 1996;106:1080.
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Otol Rhinol Laryngol 1993;102:289.
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a technique to limit blood loss during endoscopic sinus surgery. Am J Otolaryngol 1993;14:262
266.
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1995;113:204.
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1994;73:548.
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exploration. J Laryngol Otol 1994;108:171.
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sinus surgery. Laryngoscope 1999;109:546.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

36 EPISTAXIS
Head & Neck SurgeryOtolaryngology
36




EPISTAXIS
PERRY M. SANTOS
MICHAEL LEO LEPORE

P.M. Santos: Head and Neck Division, Otologic Medical Clinic, Oklahoma City, Oklahoma.
M.L. Lepore: Department of OtolaryngologyHead and Neck Surgery, University of Colorado School of
Medicine; Division of Otolaryngology, Rose Medical Center, Denver, Colorado.


Epidemiology
Anatomy
Physiology and Pathophysiology
Etiology
Local Factors
Systemic Factors
Management
Exsanguinating Epistaxis
Determination of the Epistaxis Bleeding Source
Silver Nitrate Cauterization
Electric Cauterization
Laser Photocoagulation
Nasal Packing
Balloon Packs
Greater Palatine Canal Injection
Endoscopic Management
Septoplasty
Maxillary Artery Ligation
Intraoral Ligation of the Maxillary Artery
Transantral Sphenopalatine Artery Ligation
Endoscopic Ligation of the Sphenopalatine Artery
Ligation of the Anterior and Posterior Ethmoidal Artery
External Carotid Artery Ligation
Surgical Reconstruction
Septodermoplasty
Local and Microvascular Flaps
Embolization
Preventive Measures to Avoid Epistaxis
Chapter References
Epistaxis is an alteration of normal hemostasis within the nose. Hemostasis is
compromised by mucosal abnormalities, vessel pathology, or disorders of coagulation.
Our understanding of the pathophysiology and treatment of epistaxis has increased
dramatically over the last century. Most epistaxis episodes are merely a nuisance to the
patient and are treated at home. Only a small percentage of patients are seen by medical
personnel. Most patients seeking medical assistance are easily treated and released. A
smaller subset of patients with epistaxis will have persistent recurrences, and others may
present with potentially life-threatening hemorrhage or complications. These patients
may require immediate evaluation, recognition of the etiology, and initiation of treatment
to avoid hypotension, hypoxia, anemia, aspiration, or death. Recurrent epistaxis may
represent an occult medical or surgical condition. This chapter presents the topic of
epistaxis from a pragmatic point of view. Evaluation of the patient with epistaxis and
consideration of appropriate differential diagnoses and underlying occult etiologies are
discussed. Methods of traditional and more recent innovative techniques are reviewed
and compared for effectiveness, risk, patient comfort, and expense.
EPIDEMIOLOGY
Epistaxis is the most common bleeding disorder of the head and neck region. Some
excellent older and more recent studies reveal some of the epidemiologic characteristics
and clarify some misconceptions. A U.S. health examination survey from 1972 of 6,672
adults revealed a 7% to 14% incidence of epistaxis (1). A Scandinavian survey from 1974
of 410 people found a 60% incidence of at least one episode of epistaxis during one's
lifetime, a 6% incidence requiring medical attention, and an annual incidence of 15% for
men and 9% for women (2). A Finnish study from 1974 of 1,724 patients with epistaxis
revealed a higher male incidence of 58% versus 42% for women; overall, 71% of the
patients were over 50 years of age (3). In Wales, the male-to-female ratio is 2:1 in
patients aged 20 to 49 years but was close to 1:1 for patients 50 and older (4). In addition,
they noted epistaxis occurred more frequently during the months of September through
April compared with May through August. More recently, a U.S. midwestern study found
posterior epistaxis to be more common during the colder and lower humidity months of
November through March compared with the months of April through October56%
versus 44%, respectively (5). A study within the United Kingdom demonstrated an
admission rate for epistaxis of 0.829 patients per day with outdoor temperatures less than
5C and 0.645 patients per day for temperatures between 5.1 and 10C (6). Contrary to
popular belief, hypertension has not been shown to increase one's risk for epistaxis (1,2).
However, some studies report posterior epistaxis associated with hypertension (5,7).
ANATOMY
A lucid understanding of nasal vascular anatomy is essential to effectively and safely use
newer technologies. Specifically, open surgical procedures, endoscopic evaluation with
treatment, and angiographic techniques all demand an accurate knowledge of endonasal
and maxillary anatomy and the multiple arterial systems supplying the nasal lining and
structures. Understanding and treating nasal bleeding is simplified when considering both
the involved vessels and the zones of arterioarterial anastomoses. The internal and the
external carotid artery systems supply the nose. The external carotid serves as the major
contributor (Fig. 36.1 and Fig. 36.2). The internal carotid artery supplies the anterior and
posterior ethmoid arteries (Fig. 36.3). The larger anterior and smaller posterior ethmoid
arteries branch off the ophthalmic artery within the orbit. Both arteries pass through the
periorbital fascia through the shared wall of the medial orbit and lateral fovea ethmoidalis
bone along the frontoethmoidal suture line at a level coinciding with the cribriform plate
(Fig. 36.3). The posterior ethmoid artery enters the posterior ethmoidal foramen within 4
to 7 mm of the optic nerve more than 80% of the time (8). The anterior ethmoid artery
enters the anterior ethmoidal foramen 14 to 22 mm posterior to the maxillolacrimal suture
more than 80% of the time. The distance between the anterior and posterior ethmoidal
foramina is also variable. The anterior ethmoid artery is absent 7% to 14% of the time
(8). The posterior ethmoid artery is absent 31% of the time (8). The anterior and the
posterior ethmoid vessels pass through ethmoid air cells and give rise to medial and
lateral branches. The medial branches of the ethmoid arteries supply the superior septum
and Little's area (Fig. 36.1). The lateral branches of the ethmoid arteries supply the
superior and middle turbinates (Fig. 36.2).

FIGURE 36.1. A sagittal midsection of the midface
demonstrates arteries branching off the internal carotid
artery supplying the nasal septum via the maxillary artery
and facial artery. Also depicted are the posterior and
anterior ethmoid arteries from the internal carotid artery.
Note the arterioarterial anastomosis of the anterior septal
region demonstrating Little's area and its blood supply
from the anterior ethmoid, sphenopalatine, greater
palatine, and nasal branch of the facial artery.



FIGURE 36.2. A paramedian sagittal section of the
midface demonstrates arteries branching off the internal
carotid artery and the external carotid artery supplying
the lateral nasal wall. Note the significant blood supply
from the posterior nasal artery and secondary blood
supply from the ethmoid artery supplying the middle
turbinate. Woodruff naso-nasopharyngeal plexus, at the
posterior lateral nasal wall, is supplied by the posterior
nasal artery and the pharyngeal branches of the maxillary artery.



FIGURE 36.3. An axial section of the orbital region
demonstrating the internal carotid artery, the ophthalmic
artery, and the anterior and posterior ethmoid arteries.
The orbital roof and cribriform plate have been removed
to allow exposure of the vessels. Note the relationship of
the ethmoid arteries to the globe and the optic nerve.



The external carotid artery provides blood to the nose primarily through the maxillary
artery and secondarily via the facial artery. The facial artery gives rise to the superior
labial artery, which in turn gives nasal arterial branches medially to the septum and
laterally to the ala (Fig. 36.1 and Fig. 36.2). The maxillary artery is the terminal branch of
the external carotid artery. Within the infratemporal fossa, the maxillary artery passes
either between or lateral to the superior and inferior heads of the lateral pterygoid muscle.
The artery then enters the pterygopalatine fossa inferolaterally via the ptergomaxillary
fissure. The pterygopalatine fossa is a space shaped like an inverted and elongated
pyramid. It is limited anteriorly by the posterior aspect of the maxillary sinus and the
orbital process of the palatine bone, posteriorly by the anteroinferior aspect of the greater
wing of the sphenoid bone and the pterygoid process, medially by the vertical portion of
the palatine bone, laterally by the pterygomaxillary fissure, superiorly by the sphenoid
rostrum (medially) and inferior orbital fissure (laterally), and inferiorly by the
pterygopalatine canal. Within the pterygopalatine fossa, the maxillary artery courses in a
serpentine fashion within a pad of fat. The maxillary artery and its branches are generally
more anteroinferior within the pterygopalatine fossa than the maxillary and vidian nerves,
an anatomic point that facilitates maxillary artery ligation for epistaxis. The maxillary
artery gives rise to several branches that do not generally provide blood to the nose,
including the posterior alveolar artery, the infraorbital artery, the lesser palatine artery,
and other unnamed branches. The maxillary artery terminal branches of relevance to the
subject of epistaxis within the pterygopalatine fossa are the descending or greater palatine
artery, the pharyngeal artery, the posterior nasal artery, and the sphenopalatine artery
(Fig. 36.4). The descending palatine artery may have two or three branches, the largest
serving as the greater palatine artery of the greater palatine canal. The lesser palatine
artery passes through the lesser palatine canal and foramen and supplies blood to the soft
palate. The greater palatine artery takes a circuitous course to the nose by first passing
inferiorly through the greater palatine canal and foramen and then traveling within the
lateral hard palatal mucosa. The bilateral paired arteries meet anteriorly in the midline
and pass superiorly through the single midline incisive foramen. The greater palatine
artery supplies the septum and floor of the nose (Fig. 36.1). The maxillary artery
bifurcates into the sphenopalatine and posterior nasal arteries at or distal to the
sphenopalatine foramen but may bifurcate as early as the pterygomaxillary fissure. The
sphenopalatine artery supplies the septal mucosa and in the region of the anteroinferior
septum anastomoses with the greater palatine artery, the anterior ethmoid artery, and the
nasal branches of the facial artery, thus forming Kiesselbach's plexus or Little's area (Fig.
36.1). The posterior nasal artery supplies the lateral nasal wall and the turbinates.
Superiorly it anastomoses with the ethmoid arteries. Inferiorly it anastomoses with the
pharyngeal arterial branches of the maxillary artery, thus forming the Woodruff naso-
nasopharyngeal plexus (Fig. 36.2).

FIGURE 36.4. A coronal section of the right
pterygopalatine fossa exposed after removal of the
posterior maxillary wall and the orbital process of the
palatine bone. The maxillary artery and its terminal
branches responsible for epistaxis are demonstrated
within the pterygopalatine fossa, specifically the
sphenopalatine artery, the posterior nasal artery, the
greater palatine artery, and to a lesser extent the
pharyngeal branch. The bifurcation of the sphenopalatine and posterior nasal artery can
occur proximal to the sphenopalatine foramen. (Note: Other maxillary artery
noncontributing branches are removed from the figure for clarity; see text.)



In summary, nasal cavity vascular anatomy is complex and variable with numerous
arterioarterial anastomotic systems, thus explaining in part why treatment failures and
late recurrences are common. Clearly, a greater understanding of the vascular anatomy
and possible variants will expedite successful treatment, especially in light of increasing
endoscopic evaluation and treatment by the practicing otolaryngologist.
PHYSIOLOGY AND PATHOPHYSIOLOGY
Under ideal circumstances, the design of the internal nose provides a sophisticated
conduit for laminar airflow exchange. During nasal inspiration, particulate matter is
filtered and air is humidified by the pseudostratified ciliated columnar epithelium. The
nasal lining, especially along the inferior and middle turbinates, contains a highly
vascular lamina propria. Turbinate arterioles pass within conchal bone and are
surrounded by a venous plexus. Arteriole dilation blocks venous outflow, resulting in
mucosal congestion. The submucosal plexus of veins, also known as the cavernous nasal
plexus, is similar to erectile tissue and provides rapid engorgement under
parasympathetic control from mechanical, thermal, psychogenic, sexual, or chemical
stimuli (Fig. 36.5). Septal cartilage is without an intrinsic blood supply and wholly
dependent on the overlying mucoperichondrium. Mucous and serous glands are abundant
throughout the nasal lining, especially along the turbinates. The delicate intranasal
environment is easily altered by a host of intrinsic and extrinsic factors. Secretions
provide a protective blanket for the mucosa, protecting against desiccation and loss of
ciliary activity.

FIGURE 36.5. Submucosal arterioles and plexus of
veins, also known as the cavernous nasal plexus. Note the
two- to threefold greater number of venules than
arterioles.



ETIOLOGY
Epistaxis occurs within the anterior nasal region 90% to 95% of the time (5). Most of
these cases are secondary to manipulation, relatively cold temperatures with low
humidity, and/or chronic use of nasal decongestion spray. A single and minor episode of
epistaxis with an otherwise normal history and physical examination does not warrant an
extensive evaluation. In contrast, a severe episode or recurring epistaxis should prompt a
further investigation to rule out some of the etiologies in the following discussion. It is
helpful to divide the etiologies into two broad categories: local and systemic factors
(Table 36.1).

TABLE 36.1. ETIOLOGY OF EPISTAXIS



Local Factors
Trauma is one of the most common causes of epistaxis. Children who suck their thumbs
or adults with habitual digital manipulation have a higher incidence of epistaxis of the
anterior cartilaginous nasal septum. Continuous trauma devitalizes the perichondrium,
with resultant cartilage exposure and perforation. Septal perforation induces turbulence;
impairs laminar airflow; and results in drying, scab formation, and subsequent bleeding.
Nasal skeletal trauma may be an isolated and simple nasal fracture or severe and life-
threatening midface and base of skull fractures with exsanguinating arterial hemorrhage
resulting from a motor vehicle accident. Isolated trauma in adjacent regions such as the
sinuses, orbit, and middle ear may manifest as nasal hemorrhage. Massive epistaxis in a
patient presenting with the classic triad of prior monocular blindness, ipsilateral orbital
fractures, and delayed epistaxis with a recent or distant history of head trauma should
alert the clinician to probable posttraumatic pseudoaneurysm of the internal carotid
artery. Local inflammatory reactions due to acute respiratory tract infections, chronic
sinusitis, allergic rhinitis (9), and environmental irritants, such as tobacco smoke, may
alter the normal mucosal protective blanket and underlying mucosa, allowing for dryness,
crusting, exposure, and hemorrhage. Both decongestant and steroid nasal sprays can
cause dryness and bleeding. Intranasal foreign bodies are usually encountered in children
or mentally retarded individuals. Persistent unilateral nasal symptoms of bleeding,
rhinorrhea, or foul-smelling nasal discharge strongly suggest a foreign body or tumor.
The foreign body may induce an intense inflammatory response with the formation of
friable granulation tissue. Examples of tumors associated with epistaxis in adolescent
males are juvenile angiofibroma and in the adult are nasopharyngeal carcinoma.
Septoplasty and endoscopic sinus surgery can cause epistaxis as a postoperative
complication. Nasal-prong oxygen administration and continuous positive airway
pressure therapy for obstructive sleep apnea have been associated with epistaxis. Newer
continuous positive airway pressure units have humidification available, which should
decrease this risk.
Systemic Factors
A distinct category of patients at great risk of severe and life-long epistaxis are those with
coagulation disorders and vessel pathology. Hereditary hemorrhagic telangiectasia
(HHT), also known as Osler-Weber-Rendu disease, is an autosomal dominant inherited
disorder that is pathognomonic with a positive family history, mucocutaneous
telangiectasias, and epistaxis. The pathology is characterized by thin vessel walls without
smooth muscle, increased angiogenesis resulting in vascular proliferation, arteriovenous
fistulae, and ultimately mucosal fragility. Seemingly insignificant trauma, such as nose
blowing, may lead to epistaxis. It is the most common disease of the vascular structures
leading to recurrent epistaxis. Virtually all patients are symptomatic by 40 years of age
and 62% by 16 years of age. Epistaxis was the presenting symptom of HHT in 90% of 98
patients studied. Conservative, noncauterizing, cartilage-sparing methods of hemostasis
control are recommended as initial therapy (10).
Vessel wall changes associated with aging, specifically fibrosis of the muscular tunica
media of arteries, have been implicated in epistaxis. Atherosclerosis, although commonly
assumed a risk factor, has not been specifically identified as a risk factor. Hypertension is
not considered to be a significant risk factor for anterior epistaxis, based on several
studies (1,2). However, some authors have associated hypertension as increasing the risk
of posterior epistaxis (5) or rebleeding after medical or surgical treatment (7,11).
Patients with hemostasis disorders are usually identified early in life as a result of a
history of large bruises without known trauma or prolonged bleeding after a minor cut.
The most common hereditary bleeding disorder associated with epistaxis is von
Willebrand disease (vWD). This disease is inherited in an autosomal dominant pattern
and manifests clinically with mucocutaneous hemorrhage, excessive bleeding after
trauma/surgery, and epistaxis. Epistaxis is the most common symptom of vWD, affecting
approximately 60% of those with the disorder (12). Under normal conditions, von
Willebrand factor (vWF) induces platelet aggregation when subendothelium is exposed
as in a vessel injury. The increased bleeding time seen in vWD is due to vWF being
functionally aberrant or quantitatively deficient. Although bleeding times are useful as a
screening test, laboratory diagnosis is most commonly made with quantitative
immunoelectrophoresis or enzyme-linked immunoassay. The recommended presurgical
prophylaxis in patients with vWD is desmopressin. Desmopressin has been found to
increase vWF and factor VIII levels and is recommended over cryoprecipitate (13).
Hemophilia A, the most common hemophilia, is due to a functional defect of the
procoagulant portion of factor VIII. Factor VIII is a complex of two molecules: vWF and
procoagulant factor VIII. Hemophilia B, also known as Christmas disease, is less
common and due to a deficiency of factor IX. Both have a prolonged partial
thromboplastin time and are passed on to males only by sex-linked inheritance. Epistaxis
is unusual in mild hemophiliacs but can be problematic in those with more severe forms
of hemophilia A or B. Other less common blood disorders within the differential
diagnosis of patients with hemostasis disorders are leukemia, multiple myeloma,
thrombocytopenia, and hemodialysis. Nutritional abuses or deficiencies may also be seen
with epistaxis. Alcohol has been associated with prolonged bleeding times (14).
Furthermore, alcohol abuse with poor dietary intake can lead to vitamin deficiencies and
decreased synthesis of all the coagulation factors with the exception of vWF (15).
Multiple drugs affect the normal clotting mechanism, including acetylsalicylic acid,
nonsteroidal antiinflammatory agents (16), anticoagulants (warfarin, heparin),
chloramphenicol, carbenicillin, and dipyridamole (11).
MANAGEMENT
Patients with severe uncontrolled bleeding or patients failing to adequately respond to
initial therapy are generally referred to the otolaryngologist. The degree, site, and
etiology of the epistaxis and the clinical state of the patient dictate the expediency and
aggressiveness of the initial treatment (Table 36.2 and Table 36.3).

TABLE 36.2. TREATMENT EPISTAXIS



TABLE 36.3. COMPLICATIONS EPISTAXIS
MANAGEMENT



Exsanguinating Epistaxis
Exsanguinating epistaxis is uncommon, but the condition is life threatening. These
patients frequently have severe midfacial trauma with maxillary artery laceration, often
associated with multisystem trauma. The trauma patient requires immediate evaluation
and control of the airway, followed by control of the bleeding with simultaneous fluid
and possibly blood resuscitation. Hypovolemia is recognized by inadequate tissue
perfusion (cool skin, central nervous system anxiety followed by depression, decreased
urinary output), tachypnea, and tachycardia with a narrowed pulse pressure. If
hypovolemia is suspected, immediate fluid resuscitation is initiated. Guidelines
established by the American College of Surgeons are available to recognize, treat, or
prevent ensuing hypovolemia or hypovolemic shock (17) (Table 36.4). Anterior posterior
nasal packs are placed (discussed subsequently) and if necessary followed by oro- and
nasopharyngeal packs (after the airway has been secured). The unstable midfacial
skeleton may confound the surgeon's ability to tightly pack these areas, resulting in
continued exsanguination. It may be necessary to ligate the external carotid artery, which
can be performed under local anesthesia if necessary. Persistent bleeding despite
aggressive packing may represent disseminated intravascular coagulation, which requires
early recognition and treatment. In certain cases of exsanguinating hemorrhage,
angiography with embolization will provide the optimum care. Patients with massive
epistaxis who have undergone prior sphenoid surgery may have developed a carotid
cavernous sinus fistula. Similarly, recurrent or massive epistaxis in the patient who has
suffered a head injury weeks to years earlier with resultant monocular blindness and an
orbital fracture should be evaluated angiographically to rule out a pseudoaneurysm of the
intracavernous internal carotid artery. In the past, the primary therapeutic intervention
was common or internal carotid ligation with the attendant risk of cerebral ischemia.
Ligation has for the most part been supplanted by emergent angiographic diagnosis and
life-saving embolization, with a much lower morbidity and mortality reported.

TABLE 36.4. ESTIMATED FLUID AND BLOOD
LOSSES BASED ON PATIENT'S INITIAL
PRESENTATION



Determination of the Epistaxis Bleeding Source
In contrast to the rare scenario of exsanguinating epistaxis, most patients seen by the
otolaryngologist will present with anterior or posterior epistaxis and will be
hemodynamically stable. Anterior epistaxis occurs primarily in the region of Little's area
and is more often venous in origin. Posterior epistaxis occurs primarily in the region of
the posterior septum (60% to 65%), followed in frequency by the posterior lateral nasal
wall consistent with the Woodruff naso-nasopharyngeal plexus and is more often arterial
in origin (11,18,19).
Determination of the bleeding site is most readily performed with both the patient and
physician relatively comfortable and with protective clothing and eye protection. The
patient should be in a sitting position. Identification of most anterior bleeding sites can be
accomplished with illumination and exposure from a headlight or mirror, a nasal
speculum, bayonet forceps, a Frazier suction for the nose, and a Yankauer suction for oral
cavity blood clots. If prior packing or balloons have been placed with unsuccessful
control of bleeding, the mucosa may be excoriated, and the initial bleeding site will be
more difficult to determine. Posterior bleeding sites may also be more difficult to
visualize. Identification will be facilitated after topical vasoconstrictive agents are applied
by spray or drops or on pledgets (oxymetazoline hydrochloride 0.05%, phenylephrine
hydrochloride 0.25%, or cocaine 4%). However, the agent may stop the bleeding before
identification. In fact, Krempl and Noorily (20) presented 60 patients evaluated in the
emergency department with epistaxis and treated with oxymetazoline spray only. They
reported a 65% success rate, but no duration of follow-up was discussed. Intranasal
discomfort can be decreased with lidocaine spray or cocaine 4%. If these measures do not
sufficiently control hemostasis and the bleeding site remains occult, then submucosal
injection (1% lidocaine plus 1:100,000 parts epinephrine through a 25-gauge 1.5-inch or
spinal needle) in the general vicinity of suspect bleeding will frequently slow or arrest the
bleeding to allow visualization. If the bleeding is more posterior, a 30-degree endoscope
will enhance identification; otherwise, a standard otoscope with the largest available ear
speculum will provide some magnification and illumination that may not be possible with
a headlight. If no bleeding is identified, one should still make an effort to determine the
responsible offending vessel. Finding the most prominent vessels and/or scabs and
rubbing the area with a cotton-tipped applicator to induce rebleeding facilitate this search.
Why take the effort to identify the specific bleeding site when a blind pack or balloon
could be placed? Specific bleeding site identification, although requiring greater patience
and finesse on the part of the otolaryngologist, will provide the opportunity for localized
therapy. Localized therapy, such as cauterization or a mini absorbable or
nonabsorbable pack, will provide less pain for the patient, have a lower failure rate, and
often allow for outpatient management or a shorter hospitalization. Nasal packings, by
virtue of inducing nasal mucosal edema, decrease normal mucous transport and may lead
to sinusitis. Prophylactic antibiotics are generally used while the packing is in place. A
rare but potentially lethal infectious complication, toxic shock syndrome (TSS), can
occur with various nasal packing materials. TSS is characterized by an abrupt onset of
fever, vomiting, diarrhea, hypotension, shock, rash, and subsequent desquamation.
Staphylococcus aureus frequently colonizes the nasal passage, and a small percentage of
strains may produce TSS toxin 1, the responsible toxin. Most TSS nasal cases follow
mucosal barrier violation, such as with nasal or sinus surgery, but could occur after
packing for epistaxis management. Early recognition and intervention are crucial to avoid
shock and death. Use of prophylactic parenteral antibiotics does not protect against TSS.
Silver Nitrate Cauterization
Silver nitrate is a soluble salt supplied on wooden-tipped applicators. It is extremely
useful in superficial cauterization in the anterior septum. Applying lidocaine on a small
piece of cotton over the bleeding site will obviate burning before cauterization.
Cauterization of the vessel and a 2- to 3-mm circumferential area will effectively
interrupt feeding anastomoses. To prevent further burning of normal tissue, the silver
nitrate can be neutralized with application of sodium chloride, thereby converting the
silver nitrate to silver chloride. Finally, placement of a thin layer of one of the absorbable
materials such as Surgicel, Oxycel (both oxidized regenerated cellulose), or Gelfoam
(gelatin) over the cautery site will act as a temporary scab and prevent desiccation of the
cauterized mucosa. Care should be taken to avoid contact of the silver nitrate applicator
to the nasal skin, which will temporarily discolor the skin.
Electric Cauterization
Bleeding may persist or recur after treatment with silver nitrate. This problem may be
managed with packing or electric cauterization. Local submucosal anesthesia will
decrease the pain of cautery. Electric coagulation induces a deeper penetration and more
tissue destruction than silver nitrate. Monopolar electrocautery units are malleable and
designed with suction, allowing for continuous clearing of blood from the field. Bipolar
bayonet forceps cautery in the anterior nose may allow a more controlled cauterization
with less depth of tissue injury compared with monopolar cautery. The drawback of the
bipolar bayonet forceps cautery compared with the monopolar suction cautery is the
limited access to the posterior nasal region because of the width of the bipolar forceps
handle and tip. Coaxial bipolar cautery units have become available and allow posterior
nasal cavity access but lack suction. For all types of cautery, repetitive cauterization
increases the likelihood of septal perforations. Therefore, precise identification of the
bleeding site is imperative. Light petrolatum gauze packing impregnated with antibiotic
ointment or absorbable packing (e.g., Surgicel) is useful to cover the area, decrease
infection risk, and maintain local moisture.
Laser Photocoagulation
A number of authors have reported series of patients with HHT treated with argon and
neodymium:yttrium aluminum garnet laser. Patients require multiple treatments, and
outcome is associated with the severity of the disease. This method is useful because the
biophysical properties of the neodymium:yttrium aluminum garnet laser are well suited
for this application as the treatment photocoagulates the abnormal subepithelial
arteriovenous reticulum (Fig. 36.5), preserving the overlying mucosa and underlying
cartilage.
Nasal Packing
Anterior
Anterior nasal packing can constitute a traditional ribbon gauze pack, prefabricated
expandable packs, or intranasal balloons applied to an identified or unidentified bleeding
site. Alternatively, an identified bleeding site may be managed with a mini pack applied
directly to the bleeding site, thereby decreasing patient discomfort. Anterior nasal
hemorrhage is usually easy to locate and manage, but if a severe septal deviation exists
and the site cannot be identified, then a traditional anterior pack may provide hemostasis.
A septoplasty, preferably elective, is recommended to the patient, because the associated
turbulence may exacerbate the risk of recurrent epistaxis. The traditional anterior pack of
petrolatum gauze (0.5 72 inch) coated with an antibacterial ointment is firmly packed in
a layered fashion toward the posterior choanae after decongestion and local anesthesia
placement (Fig. 36.6). Local anesthesia, in addition to decreasing discomfort, may
decrease the risk of apnea, bradycardia, and hypotension by blocking the nasal-vagal
reflex. Alternatively, Telfa packing can be coated with antibacterial ointment, rolled, and
placed into the nasal cavity. If technically possible, placing a single layer of absorbable
material such as Surgicel, Oxycel, or Gelfoam over the known bleeding site first followed
by the packing material may prevent rebleeding after pack removal 2 to 4 days later.
Newer nasal packing materials have become available that expand several times in
volume with hydration, making placement easier for the physician and patient. These
hydrophilic and compressed materials are generally made of hydroxylated polyvinyl
acetal (Merocel) and polyvinyl alcohol (Expandacell, Rhino Rocket). A prospective
randomized trial comparing Merocel nasal packing with ribbon gauze impregnated with
bismuth subnitrate and iodoform paste for the control of epistaxis demonstrated no
difference in insertion or removal discomfort, hemostasis, or complications in a
population of 49 patients (21).

FIGURE 36.6. Sagittal section demonstrates technique
for placement of traditional anterior nasal pack.



Patients with chronic mucosal pathology from HHT, coagulation disorders, or leukemia
should be managed without packing, if possible, in light of the chronicity of the
underlying pathology and in anticipation of future multiple treatments. Avitene
(microfibrillar cross-linked bovine topocollagen) use for initially arresting bleeding in
patients with HHT, thrombocytopenia, or septal perforations was successful in 38 of 49
patients with no reported complications (22). Surgicel, Oxycel (oxidized regenerated
cellulose), and Avitene are all effective as minimally invasive packs. An additional
benefit has been obtained with the use of thrombin spray applied to Gelfoam or Surgicel.
Posterior
Posterior nasal packing is indicated for those patients failing anterior nasal packs or who
upon evaluation have known posterior bleeding. Posterior nasal packs require careful
instruction to the patient before beginning the procedure because of discomfort and
airway manipulation. Intravenous access and mild sedation are recommended if not
medically contraindicated. Some patients may need to be taken to the operating room to
place a proper pack. The ideal pack will seat firmly in the posterior nasal cavity against
the septum and floor of the nose. It should not fill the nasopharynx or depress the soft
palate, because this significantly increases discomfort, obstructs the contralateral nasal
airway, and may increase the risk of hypoventilation. The posterior pack is generally used
in conjunction with an anterior pack, because the main purpose of the posterior pack is to
stabilize the anterior packing (Fig. 36.6 and Fig. 36.7). When a patient bleeds around a
well-placed anterior nasal pack, one recommended technique is the greater palatine
foramen block (described subsequently), which provides anesthesia and a tamponading
effect, followed by the posterior pack. All patients with a posterior pack should be
admitted and monitored in an appropriate hospital setting. Pulse oximetry is
recommended to follow oxygen saturation. Patients will experience difficulty in
swallowing, so maintenance of body fluids is important. Deep vein thrombosis in the
bedridden and elderly patient is of particular concern; therefore, elastic stockings may be
used as a preventive measure. The gauze packing should be impregnated with antibiotic
ointment, which will decrease the microbial flora present. The packing is usually left in
position for an average of 3 to 5 days. To remove the packing, the procedure outlined in
Fig. 36.7 is reversed. A tongue blade is used to depress the tongue while the string or
pacing in the posterior pharynx is grasped with a curved clamp and removed. If patients
fail packing, they are candidates for further intervention described subsequently or the
physician may undertake a different initial procedure based on the clinical presentation.

FIGURE 36.7. Sagittal section demonstrates posterior
nasal-packing procedure. A: Pass a red rubber catheter
through the nostril until visible in oropharynx. Grasp the
catheter and tie the two 1-0 silk ties from the posterior
pack to the catheter tip. B: Pull the catheter in the nostril
back out the nose and temporarily secure the strings with
clamps. Place an anterior pack. C: Secure the two 1-0 silk
ties over a dental roll to maintain forward pressure of the
posterior nasal pack. D: Sagittal plane of the final position of the anterior and posterior
packs.



Balloon Packs
Balloon packs for epistaxis have become more available and varied than the first Foley
catheter balloon used. The concept is the same as traditional nasal packing; by placement
of air or saline into the balloon, pressure is applied to the lateral nasal wall and septum.
Newer types of nasal balloon packs include double balloons, a composite of balloon and
Merocel that has an advantage of staying in place after balloon deflation and removal.
Some nasal balloons allow continued respiration through an integrated hollow center. A
potential drawback of balloon packs is the inability to place pressure against the actual
site of bleeding, because it is a blind pack like the anterior and posterior pack. Also,
alar or columellar necrosis can occur if the pack exerts too much pressure laterally or
medially.
Greater Palatine Canal Injection
Greater palatine canal injection is a dental anesthetic injection technique of the greater
palatine foramen/canal that can be used to control posterior nasal hemorrhage involving
the sphenopalatine artery (Fig. 36.2). Bharadwaj (23) studied the greater palatine canal in
cadavers and skulls and reported his recommendations and clinical findings for the
technique of 1% lidocaine or sterile water injection. Of 55 patients receiving the
injection, 90% had initial control, but bleeding recurred in 40% of those initially treated
within 24 hours. These patients were reinjected one to eight more times with ultimate
control. He found no difference in those patients injected with lidocaine versus water.
The high pressures used in the canal to tamponade the bleeding can potentially injure the
greater palatine nerve as well.
Endoscopic Management
The advent of fiberoptic illumination and visualization of the intranasal regions not
readily seen with a headlight or nasal speculum have introduced a new era of managing
epistaxis. Flexible fiberoptic nasopharyngoscope was initially used to direct cauterization
efforts. The flexible scope allowed excellent visualization of the posterior nasal cavity
but was cumbersome when cauterizing the bleeding site. More recently, El-Silimy (18)
reported a series of 27 patients with posterior epistaxis successfully treated using
endoscopes under local anesthesia and meperidine hydrochloride. His technique used the
2.7-mm diameter 0-, 30-, and 70-degree angled endoscopes to identify the bleeding site.
He injected 1% lidocaine with 1:100,000 parts epinephrine submucosally and then
cauterized with a bipolar or monopolar insulated cautery. Two patients required nasal
packing at the time of cauterization, and one patient experienced recurrent epistaxis 3
months later, which was controlled with cauterization. In a prospective study of the
management of posterior epistaxis comparing traditional packing techniques versus
endoscopic hemostasis with cautery, McGarry (19) demonstrated fewer treatment
failures, no complications, and significantly shorter hospitalizations (2.7 vs. 4.5 days; P
.05) for endoscopic management versus packing techniques. Of note, all endoscopic cases
were treated with local anesthesia without going to the operating room. Elwany and
Abdel-Fatah (24) reported endoscopic control of posterior epistaxis in 26 of 38 patients
with monopolar suction cautery. The most severe complication was temporary palatal
numbness in the distribution of the greater palatine nerve in three patients. More studies
comparing the endoscopic management to other modalities of therapy are required to
confirm these preliminary studies indicating good short- and long-term success and cost
effectiveness.
Benefits of posterior epistaxis endoscopic management are precise localization of the
bleeding site and direct visualization of the injection, cauterization, lasering, or packing
compared with other blind packing techniques and ability to manage select patients
with local anesthesia without the need for the operating room. Treatment can be localized
to a smaller area in contrast to balloon or gauze packing. As a result, the patient has less
discomfort. The disadvantages of endoscopic management of epistaxis are the expertise
required compared with that required for nasal packing; the expense and limited
availability of proper instrumentation in emergency departments, where most of these
patients are encountered; and the necessity of taking some of these patients to the
operating room because of instability of the patient or unavailability of proper
instruments in the emergency department.
Septoplasty
A septoplasty may sometimes be necessary as an initial procedure before using nasal
packing if a severe cartilaginous or bony deformity prevents proper insertion of the
packing. Patients with recurrent epistaxis with straight septums may still benefit from
septoplasty, which appears to decrease the rate of future bleeding.
Maxillary Artery Ligation
Maxillary artery ligation causes a decrease in the intravascular pressure gradient,
resulting in hemostasis of the posterior nasal cavity unless anastomoses exist with
continued high pressures. Briefly described, the transantral maxillary artery ligation is
actually a ligation of the maxillary artery and the distal branches: the descending palatine,
the sphenopalatine, and the posterior nasal arteries and to a lesser extent the pharyngeal
branch. The sphenopalatine and the posterior nasal arteries may bifurcate at the
sphenopalatine foramen (most common) or much earlier, requiring identification and
ligation to prevent failures. Through a Caldwell-Luc approach, the posterior maxillary
sinus wall is identified and a laterally based U-shaped mucosal incision created. The
posterior maxillary wall is removed. The area is enlarged with small mastoid curettes. An
operating room microscope or surgical loops provide the magnification required to
remove fat and identify and clip the vessels within the pterygopalatine fossa (Fig. 36.4).
The orbital process of the palatine bone is removed to gain exposure of the
sphenopalatine foramen and the arterial vessel(s) and expose any anastomoses from the
pharyngeal artery. Many authors recommend combining anterior ethmoid artery ligation
with maxillary artery ligation (7,25). However, McDonald and Pearson (26) evaluated
their patients long term and found no additional benefit with anterior ethmoid artery
ligation. A review of several studies using transantral ligation of the maxillary artery
revealed an overall average success rate of 87% (27). In an investigation to evaluate
surgical control, Metson and Lane (7) identified rebleeding after maxillary artery and
concurrent vessel ligation (ethmoid or external carotid) in 15 of 100 patients. The most
common reason for postoperative rebleeding was failure to identify or fully close the clip
on the maxillary artery. They also found that age, anemia, and a history of hypertension
appeared to be predictive of surgical failures.
Various authors have considered at what point surgical intervention should be considered
when treating epistaxis. Wang and Vogel (28) reviewed the management of patients with
epistaxis treated with posterior nasal packing compared with those treated with ligation.
They found a greater failure rate (26% vs. 14%), complication rate (69% vs. 40%), and
length of hospitalization (8 vs. 6 days) in patients managed with packing versus ligation.
Packing complications included hypoxia, sepsis, respiratory obstruction, and arrhythmia-
ischemia. The authors recommended ligation as a first line of therapy for posterior nasal
epistaxis. In contrast, Schaitkin et al. (25) reported different findings and
recommendations. They compared epistaxis patients managed medically (posterior nasal
packing) with those failing treatment and requiring maxillary artery and anterior ethmoid
artery ligation. They reported a higher and more severe complication rate, longer hospital
stay, and greater costs in patients requiring surgery versus those receiving medical
treatment only. Based on their experience, they recommended surgical management if the
patient failed medical management after 72 hours. A study by Shaw et al. (29) comparing
surgical with medical management demonstrated similar findings to the study of
Schaitkin et al. with regard to longer hospitalization in surgical patients and made similar
recommendations of medical management for 72 hours followed by surgery in cases of
failures and in those patients requiring more than three units of blood transfusion. Barlow
et al. (30), in a study group of 44 patients admitted with epistaxis, determined that the
subset with a low hematocrit (less than 38%), posterior site of bleeding, or having had a
blood transfusion were predictive of those most likely to require surgical management.
Intervention included arterial ligation, endoscopic cautery, and embolization, all with
similar rebleed rates (20% to 33%).
Intraoral Ligation of the Maxillary Artery
In 1984, Maceri and Makielski (31) described an intraoral approach to ligate the
infratemporal portion of the maxillary artery. The procedure is useful in children as an
alternative to embolization and external carotid artery ligation for removal of vascular
tumors. It is also useful to control severe bleeding during a maxillectomy where a
Caldwell-Luc procedure is contraindicated to prevent tumor spill. The technique involves
exposing the posterior portion of the maxilla through a posterior gingivobuccal incision.
A finger is inserted into the depths of the wound to palpate the maxillary artery. The
nerve hook is used to deliver the artery for ligation.
Transantral Sphenopalatine Artery Ligation
In 1982, Simpson et al. (32) described a modified Caldwell-Luc approach to ligate the
sphenopalatine artery while avoiding entrance into the pterygopalatine fossa. The medial
posterior inferior maxillary wall is removed, and the sphenopalatine artery and the vidian
nerve are exposed. The vidian nerve is dissected free and the vessel ligated. The reported
advantage of distal sphenopalatine artery ligation is diminished risk of failure due to
collateral circulation.
Endoscopic Ligation of the Sphenopalatine Artery
White (33) reported an endoscopic modification of Simpson's technique of isolation and
ligation of the sphenopalatine artery through a meatal antrostomy and canine fossa
sinuscopy approach in two patients. Other authors reported on larger series with good
results and a low complication rate in patients with refractory epistaxis (34). In the hands
of skilled endoscopic surgeons, this technique may replace transantral approaches as the
surgical treatment of choice.
Ligation of the Anterior and Posterior Ethmoidal Artery
The anterior and posterior ethmoid arteries can be ligated to decrease blood flow to the
upper nasal vault from the internal carotid artery system (Fig. 36.1, Fig. 36.2, Fig. 36.3,
and Fig. 36.8). It is generally performed in conjunction with ligation of the maxillary
artery or the external carotid artery. Anterior and posterior ethmoid artery anatomy and
ligation were first described by Kirchner et al. (8) in 1961. A circumlinear incision is
normally made between the inner canthus and midline of the nose (Lynch incision). The
periosteum is incised and elevated. The frontoethmoidal suture line is followed in a
posterior direction about 14 to 22 mm to the anterior ethmoid artery and its foramen (Fig.
36.8). The artery can be managed by bipolar cautery or neurosurgical clips before
division. The posterior ethmoid artery is further posterior at a highly variable distance.
The optic nerve lies 4 to 7 mm more posterior to the posterior ethmoidal foramen.
Despite newer technologies (e.g., angiography), ethmoid artery ligation remains an
important surgical procedure in that no other procedure can access these branches of the
ophthalmic artery.

FIGURE 36.8. Technique of anterior ethmoid artery
ligation.



External Carotid Artery Ligation
Ligation of the external branch of the carotid artery is a relatively straightforward
approach to decreasing blood flow to the more distal maxillary artery compared with
sphenopalatine artery ligation by one of the aforementioned procedures. Another
advantage is the rapidity with which the procedure can be accomplished under local
anesthesia in patients who are poor anesthetic risks and in patients with exsanguinating
epistaxis. The disadvantage is the lack of control of potential collateral circulation, which
will maintain high maxillary artery blood pressures. The procedure is carried out by
exposing the common carotid artery along the anterior border of the sternocleidomastoid
muscle with identification and preservation of the internal jugular vein and vagus nerve.
The bifurcation of the common carotid artery is identified. The ascending pharyngeal,
thyroid, and lingual arteries are identified to distinguish the external carotid artery from
the internal carotid artery. Suture ligation of the external carotid artery is performed with
heavy silk. In a 10-year follow-up of patients undergoing external carotid artery ligation,
45% of the patients failed treatment (35). However, another study reported a 9-year
follow-up with a 7% failure rate in patients undergoing external carotid artery and
anterior ethmoidal artery ligation without any significant complications (36).
Surgical Reconstruction
Surgical reconstructive procedures are generally reserved for patients with severe and
recalcitrant HHT. These procedures also have applications in patients with chronic septal
ulcers or septal perforations, in patients with vWD, and in patients who have had ablative
tumor surgery, in which case the procedure is used to resurface the nasal cavity after it
was denuded of the mucosal lining.
Septodermoplasty
Septodermoplasty is a grafting technique whereby the telangiectatic mucosal surfaces are
removed with preservation of the perichondrial and periosteal vascular bed. Split-
thickness skin is grafted and antibiotic-impregnated gauze packing applied. Surgical
failure with recurrent epistaxis in septodermoplasty surgery is usually related to
inadequate graft coverage at the initial surgery, shrinkage of the graft with exposed
telangiectatic areas, or ingrowth of the telangiectasia into the skin graft itself.
Local and Microvascular Flaps
Median forehead flaps and nasolabial flaps have been used to resurface the interior lining
of the nasal cavity in the case of recalcitrant extensive HHT. The radial forearm free flap
has also been used to resurface the demucosalized nasal cavity after severe epistaxis in a
patient with HHT. A major advantage of these flaps is their thickness, which can resist
ingrowth of telangiectasias compared with skin grafts. The disadvantages of flaps and
skin grafts relate to the need for a lateral rhinotomy and resultant facial scars and
intranasal chronic desquamation. Patients may complain of a foul-smelling thick nasal
discharge and crusting. Continuous saline douches or irrigations using a water pick are
necessary. Nasal airflow is limited by the thickness of the graft. Another approach to
decreasing epistaxis in patients with HHT is nasal aperture closure in an attempt to
decrease airflow and drying.
Embolization
In 1974, Sokoloff et al. (37) reported percutaneous angiography and selective
embolization of the maxillary artery for localizing and controlling recalcitrant epistaxis.
Most cases of recurrent epistaxis involve the maxillary distal branches; thus, isolated
embolization of these will control most recalcitrant cases. Vitek (38) reported 87%
control of epistaxis with isolated distal branch maxillary artery embolization. Additional
embolization of the facial artery resulted in 97% control. Some of the largest series
reporting angiographic embolization for the treatment of recalcitrant posterior epistaxis
demonstrated control of hemorrhage in 88% of 81 patients treated emergently (39), 96%
of 54 patients (40), and 88% of 107 patients (41). In general, short-term failures due to
internal carotid branches were attributed to dominant anterior and/or posterior ethmoid
arteries requiring external surgical ligation for control. Short-term failures due to external
carotid artery branches were attributed to dominant ipsilateral facial arteries or
contralateral collateral maxillary artery branches. More than half of the long-term failures
were attributed to patients with HHT in the study of Elden et al. (39). These studies
reported the advantages of angiography and embolization as shorter hospitalizations,
local versus general anesthesia, treatment of surgically inaccessible vessels, treatment of
surgical failures due to development of arterioarterial anastomotic collaterals, and
relatively high success rates. The technique is not as useful in cases of ethmoid artery
bleeding, vascular anomalies, or severe atherosclerosis. Also, the technique is not
available at all centers. Numerous embolization materials are used, including polyvinyl
alcohol, Gelfoam particles, and coiled springs. Potential but rare complications include
skin necrosis, blindness, ophthalmoplegia, facial pain or edema, paresthesias or paralysis,
and cerebral embolization with hemiplegia. Groin hematoma is the most common
complication. Two series reported a single case of a cerebrovascular accident (39,41) and
one case of retinal artery occlusion (39). Strong et al. (27) retrospectively compared
transantral maxillary artery ligation with embolization by reviewing multiple factors
between patients failing medical management. The overall success rate, complication
rate, and cost of treatment for both procedures were approximately the same. Strong et al.
recommended individualizing treatments based on patient criteria and embolization for
patients who are an anesthetic risk, such as in patients with cardiovascular instability.
They recommended transantral maxillary ligation for patients with presumed ethmoidal
artery bleeding that could not be treated with embolization, with severe atherosclerosis
limiting angiocatheter access, or in centers where interventional radiography is not
available.
PREVENTIVE MEASURES TO AVOID EPISTAXIS
Patient education will help prevent many episodes of epistaxis. A careful discussion of
the importance of humidification in dry climates; restraining from the practice of digital
manipulation; avoidance of airborne irritants, dander, and smoke; and control of allergies
may avert many episodes of epistaxis. Locally placed petrolatum or antibiotic ointment
may help those with dry intranasal mucosa. Physician precautionary measures include
tapering amount of nasal spray usage (e.g., nasal steroids) to obtain maximal therapeutic
benefit but decrease risk of nasal mucosal dryness and epistaxis, nasal mucosal
vasoconstriction with oxymetazoline before nasal intubation (shown to decrease the
incidence of epistaxis during intubation and extubation), presurgical prophylaxis with
desmopressin in patients with vWD, and intranasal surgical technical refinements
(decreases number of postoperative epistaxis episodes).

HIGHLIGHTS
Exsanguinating epistaxis requires early intervention with
airway and circulatory support and hemorrhage control with
packing, ligation, and/or embolization.
Evaluate the patient with epistaxis considering both local and
systemic underlying etiologies, not just the site of bleeding.
Before examining the nose with epistaxis, have instruments and
packing materials available, an exact treatment plan, and a
backup treatment plan if the initial treatment fails. Attempt to
localize the exact bleeding site: anteriorly with the nasal
speculum and posteriorly with an endoscope or otoscope.
If cautery fails or does not appear to be an option, attempt a
mini pack placement. Keep in mind the complex and variable
nasal artery anatomy with the numerous arterioarterial
anastomotic systems.
Studies to date suggest the optimum therapy in the management
of epistaxis should begin with a conservative approach of
hemorrhage control (cautery or packing), patient comfort, and
outpatient management if possible. If patients fail packing after
approximately 3 days or are requiring transfusions, then
surgical intervention or angiography with embolization should
be considered.
The decision between surgery and embolization should be
based on individual patient criteria. Each procedure has distinct
advantages over the other.
Attempt to manage patients with known coagulation or vessel
disorders conservatively considering their life-long challenge of
future recalcitrant epistaxis. Escalate treatment as dictated by
their lack of response to simpler means.
The placement of posterior nasal packs may predispose patients
toward apnea and bradycardia. Careful monitoring of these
patients is mandatory.
All procedures used to control epistaxis have potential
associated complications that must be considered in the overall
treatment approach.
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37. Sokoloff J, Wickbom I, McDonald D, et al. Therapeutic percutaneous embolization in intractable
epistaxis. Radiology 1974;111:285287.
38. Vitek J. Idiopathic intractable epistaxis: endovascular therapy. Radiology 1991;181:113116.
39. Elden L, Montanera W, Terbrugge K, et al. Angiographic embolization for the treatment of
epistaxis: a review of 108 cases. Otolaryngol Head Neck Surg 1994;111:4450.
40. Elahi MM, Parnes LS, Fox AJ, et al. Therapeutic embolization in the treatment of intractable
epitaxis. Arch Otolaryngol Head Neck Surg 1995;121:6569.
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114 cases. Laryngoscope 1998;108:615619.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

37 ANATOMY AND PHYSIOLOGY OF THE SALIVARY GLANDS
Head & Neck SurgeryOtolaryngology
37




ANATOMY AND PHYSIOLOGY OF THE
SALIVARY GLANDS
THEDA C. KONTIS
MICHAEL E. JOHNS

T.C. Kontis: Department of OtolaryngologyHead and Neck Surgery, Facial Plastic Surgicenter, Johns
Hopkins Medical Institutions, Baltimore, Maryland.
M.E. Johns: The Robert W. Woodruff Health Sciences Center, and Emory Healthcare, Emory University,
Atlanta, Georgia.


Developmental Anatomy
Anatomy of the Salivary Glands
Parotid Gland
Facial Nerve
Great Auricular Nerve
Auriculotemporal Nerve
Arterial Supply
Venous Drainage
Lymphatic Drainage
Submandibular Gland
Sublingual Gland
Minor Salivary Glands
Physiology of the Salivary Glands
Production of Saliva
Autonomic Innervation
Salivary Flow Rates
Radiographic Imaging
Chapter References
The major salivary glands in humans consist of the paired parotid, submandibular, and
sublingual glands. In addition, hundreds of minor salivary glands line the entire oral
cavity. Their main role is the production of saliva, which aids in digestion, protects the
mucosa from desiccation, protects against dental caries, and assists in the maintenance of
homeostasis. The head and neck surgeon should be familiar with the anatomic
relationships of the glands and their innervation and the physiology of secretion. In
addition, an understanding of gland embryology is important in tumor histogenesis.
DEVELOPMENTAL ANATOMY
The major salivary glands develop in the sixth to eighth weeks of embryonic life as
outpouchings of oral ectoderm into the surrounding mesenchyma (Fig. 37.1). The
primordia originate at the sites of the eventual duct orifices, and as they grow they
develop into elaborate tubuloacinar systems. The parotid anlage grows posteriorly as the
facial nerve advances anteriorly and eventually surrounds the nerve with glandular tissue.
As the mesenchymal capsule surrounds the gland, it entraps lymph nodes and sends
projections into the gland itself. The minor salivary glands arise from oral ectoderm and
nasopharyngeal endoderm and form simple tubuloacinar systems.

FIGURE 37.1. Development of the major salivary glands
in 8- and 10-week embryos (axial section). SMa,
submandibular anlage; SLa, sublingual anlage. (From
Meyerhoff WL, Rice DH. Salivary gland anatomy and
physiology. In: Paparella MM, Shumrick DA, Meyerhoff
WL, eds. Otolaryngology-head and neck surgery, 3rd ed.
Philadelphia: W.B. Saunders, 1992, with permission.)



ANATOMY OF THE SALIVARY GLANDS
Parotid Gland
The parotid gland is the largest of the major salivary glands and lies in the preauricular
region deep to skin and subcutaneous tissues (Fig. 37.2). Its acinar cells are mainly of the
serous secreting type. The facial nerve divides the gland, by definition, into a large
supraneural gland and a smaller infraneural component. The parotid compartment is the
triangular space that contains the parotid gland and its associated vessels, nerves, and
lymphatics. The parotid compartment is bounded superiorly by the zygoma; posteriorly
by the external auditory canal; and inferiorly by the styloid process, the styloid muscles,
and the internal carotid and jugular vessels. The anterior margin of the gland forms a
diagonal from the gland's superior to posterior boundaries superficial to the masseter
muscle. In addition, a small tail of parotid tissue extends posteriorly toward the mastoid
process and overlays the sternocleidomastoid muscle.

FIGURE 37.2. The parotid gland and the facial nerve.
Note that the nerve exits the stylomastoid foramen lateral
to the styloid process. Also note the relationship of the
nerve branches to the surrounding structures.



The Stensen duct arises from the anterior border of the gland, 1.5 cm below the zygoma.
The duct, which courses approximately 4 to 6 cm, runs anteriorly across the masseter
muscle, turns medially and pierces the buccinator muscle, and ultimately opens
intraorally just opposite the second upper molar. The buccal branch of the facial nerve
travels with the duct.
The parotid fascia is a continuation of the superficial layer of deep cervical fascia and is
divided into superficial and deep layers. The dense superficial fascia extends from the
surrounding musculature, from the masseter anteriorly and the sternocleidomastoid
posteriorly, and extends superiorly to the zygoma. The fascia sends septa into the
glandular tissue, which prevents separation of a surgical plane between the gland and its
fascia. Because of the presence of this inelastic capsule, a suppurative or other expansive
process in the parotid gland requires surgical drainage.
The deep layer of parotid fascia extends from the fascia of the posterior portion of the
digastric muscle and forms the stylomandibular membrane (Fig. 37.3). The membrane
separates the parotid gland from the submandibular gland and stretches from the
mandible anteriorly, from the stylomandibular ligament inferiorly, and from the styloid
process posteriorly. Occasionally, parotid tissue can herniate through a weakness in the
stylomandibular membrane and lie in the lateral pharyngeal wall. For this reason, tumors
deep in the parotid gland can present as parapharyngeal masses.

FIGURE 37.3. Stylomandibular membrane (deep layer
of parotid fascia). Herniations of parotid tissue through
this membrane can result in a parapharyngeal mass.



Facial Nerve
The facial nerve exits the skull base from the stylomastoid foramen, which lies lateral to
the styloid process and medial to the mastoid tip. The facial nerve gives off three motor
branches as it exits the stylomastoid foramen: to the stylohyoid muscle, to the
postauricular muscle, and to the posterior belly of the digastric muscle. The nerve can be
identified by its relationship to the surrounding structures. The tragal pointer is a
projection of conchal cartilage that points medially toward the stylomastoid foramen. The
nerve lies approximately 6 to 8 mm anteroinferior to the tympanomastoid suture line.
After it exits the stylomastoid foramen, the facial nerve then turns laterally to enter the
parotid gland posteriorly. It branches at the pes anserinus (goose's foot) into an upper
temporofacial and lower cervicofacial division. The pes is usually about 1.3 cm from the
stylomastoid foramen. The two subdivisions then branch to form the five major branches:
temporal, zygomatic, buccal, marginal mandibular, and cervical. There are often small
internerve communications among the buccal, zygomatic, and temporal branches and
normal anatomic variations in the branching patterns (Fig. 37.4).

FIGURE 37.4. Normal variation in branching patterns of
the facial nerve. (From Pogrel M, Schmidt B, Ammar A.
The relationship of the buccal branch of the facial nerve
to the parotid duct. J Oral Maxillofac Surg 1996;54:71,
with permission.)



When the normal anatomy is distorted, as when tumor is present, the facial nerve can be
identified from several constant relationships. The buccal branch of the facial nerve
follows the course of the parotid duct and lies either superior or inferior to the duct (1).
The temporal branch crosses the zygomatic arch parallel with the superficial temporal
vessels. The marginal mandibular branch runs along the inferior border of the gland
superficial to the posterior facial vein (retromandibular vein). Each branch can be
identified distally and then followed proximally through the gland to the main trunk of
the nerve. Occasionally, if the main nerve trunk cannot be identified by the usual
landmarks, a mastoidectomy can be performed to identify the nerve as it exits the
stylomastoid foramen.
Great Auricular Nerve
The great auricular nerve supplies sensation to the posterior surface of the pinna and the
ear lobule. It is the largest branch of the cervical plexus and is often divided during
parotidectomy. It passes around the posterior border of the sternocleidomastoid muscle
and then travels superiorly toward the pinna. This nerve can be harvested and used, if
needed, for facial nerve grafting.
Auriculotemporal Nerve
The auriculotemporal nerve is a branch of the mandibular (third) division of the
trigeminal nerve. It exits by way of the foramen ovale, turns superiorly, anterior to the
external auditory canal, and parallels the superficial temporal vessels to innervate the
scalp. The nerve carries postganglionic parasympathetic fibers from the otic ganglion to
the parotid gland, which stimulates secretion. When injured during parotidectomy,
aberrant innervation to the skin can result in gustatory sweating (Frey syndrome).
Arterial Supply
The external carotid artery provides the major blood supply to the parotid gland. The
artery runs cephalad, parallel with the mandible, and bifurcates into its two terminal
branches (maxillary and superficial temporal arteries) at the level of the mandibular
condyle. The transverse facial artery, a branch of the superficial temporal artery, supplies
the parotid gland, Stensen duct, and the masseter muscle. It is accompanied by the
transverse facial vein and travels anteriorly between the zygomatic arch and the parotid
duct.
Venous Drainage
The superficial temporal vein joins the maxillary vein to form the posterior facial
(retromandibular) vein. The posterior facial vein is the major venous drainage of the
parotid and lies deep to the facial nerve. The vein runs lateral to the carotid artery and
emerges at the lower pole of the gland. It then joins the postauricular vein to form the
external jugular vein. Also, the posterior facial vein joins the anterior facial vein to form
the common facial vein, which ultimately empties into the internal jugular system.
Lymphatic Drainage
The parotid gland is the only salivary gland with two layers of nodes. The superficial
layer, consisting of approximately 3 to 20 nodes, lies between the gland and its capsule.
These nodes drain the parotid gland, external auditory canal, pinna, scalp, eyelids, and
lacrimal glands. The second layer of nodes lies deep in parotid tissue and drains the
parotid gland, external auditory canal, middle ear, nasopharynx, and soft palate. More
lymph nodes are present in the superficial lobe of the parotid as compared with the deep
lobe (7.6 vs. 2.3). The two systems empty into the superficial and deep cervical lymph
systems.
Submandibular Gland
The second largest major salivary gland is the submandibular (submaxillary) gland. It
comprises both mucous and serous cells. The gland lies in the submandibular triangle,
which is formed by the anterior and posterior bellies of the digastric muscle and the
inferior margin of the mandible (Fig. 37.5). The gland lies medial and inferior to the
mandibular ramus and wraps around the mylohyoid muscle in a C-shaped fashion to
produce a superficial and deep lobe (Fig. 37.6).

FIGURE 37.5. The submandibular triangle. Note the
relationship of the marginal mandibular nerve to the
mandible and facial vessels.



FIGURE 37.6. The superficial and deep lobes of
submandibular gland are separated by the mylohyoid
muscle. The sublingual gland has multiple ducts that open
along the plica of the floor of the mouth.



The superficial lobe of the submandibular gland lies in the lateral sublingual space. The
deep lobe of the gland (actually first encountered during a routine submandibular gland
excision) lies inferior to the mylohyoid muscle and constitutes the bulk of the gland. The
superficial layer of deep cervical fascia splits to envelop the gland. Wharton duct exits
from the medial surface of the gland and travels between the mylohyoid and hyoglossus
muscles onto the genioglossus muscle. It then opens intraorally lateral to the lingual
frenulum at the floor of the mouth. The duct is approximately 5 cm in length. As the duct
exits the gland, the hypoglossal nerve lies inferiorly and the lingual nerve superiorly.
The submandibular gland is innervated by the sympathetic nervous system (SNS) and
parasympathetic nervous system (PNS), which stimulate the gland to produce mucoid and
watery saliva, respectively. The parasympathetic supply is from the chorda tympani
nerve, which is a branch of the facial nerve. The chorda carries preganglionic
parasympathetic fibers to the submandibular ganglion by means of the lingual nerve. At
the submandibular ganglion, the fibers synapse onto postganglionic parasympathetic
fibers that stimulate the gland to produce saliva. The sympathetic fibers originate in the
superior cervical ganglion and travel with the lingual artery to the gland.
The facial artery provides the major blood supply to the gland. The artery, which is a
major branch of the external carotid artery, grooves the deep portion of the
submandibular gland as it courses superiorly and anteriorly. At the superior aspect of the
gland, it passes laterally and curves around a notch in the mandible to supply the face.
The anterior facial vein drains the gland. The marginal mandibular branch of the facial
nerve lies superficial to the anterior facial vein. Ligation of the vein and retraction
superiorly are one technique used to protect the nerve during submandibular gland
excision.
Lymph nodes are present between the gland and the capsular fascia but not deep in
glandular tissue. The nodes drain into the deep cervical and jugular chains.
Sublingual Gland
The sublingual gland is the smallest of the major salivary glands and lies just below the
floor of mouth mucosa (Fig. 37.6). It contains primarily mucus-secreting acinar cells. The
gland is bordered by the mandible and genioglossus muscle laterally and the mylohyoid
muscle inferiorly. The submandibular duct and lingual nerve travel between the
sublingual gland and the genioglossus muscle. In contrast to the parotid and
submandibular glands, no true fascial capsule surrounds the sublingual gland.
Approximately 10 small ducts (ducts of Rivinus) exit the superior aspect of the gland and
open intraorally along the sublingual fold or plica of the floor of the mouth. Occasionally,
several of the ducts may join to form a major sublingual (Bartholin) duct, which then
empties into Wharton duct.
Like the other major salivary glands, the sublingual gland is innervated by both the SNS
and PNS. The lingual nerve carries postganglionic parasympathetic fibers to the gland
from the submandibular ganglion. The facial artery carries the sympathetic fibers from
the cervical ganglion. The sublingual branch of the lingual artery and the submental
branch of the facial artery provide the blood supply to the sublingual gland. The venous
drainage is by the corresponding veins. The major lymphatic drainage is to the
submandibular nodes.
Minor Salivary Glands
The minor salivary glands are mucous, serous, or mixed glands that line the entire oral
cavity and number about 600 to 1,000. Each gland has its own simple duct that empties
directly into the oral cavity. The glands are concentrated in the buccal, labial, palatal, and
lingual regions. They can also be found in the superior pole of the tonsils (Weber glands),
tonsillar pillars, and base of the tongue. Minor salivary gland tumors most often arise in
glands located in the palate, upper lip, and cheek.
The blood supply, venous drainage, and lymphatic drainage of the glands correspond to
those of the region of the oral cavity in which the glands are located. Most glands receive
parasympathetic innervation from the lingual nerve; however, the glands located in the
palate receive their supply from the sphenopalatine ganglion by way of the palatine
nerves.
PHYSIOLOGY OF THE SALIVARY GLANDS
The major function of the salivary glands is the production of saliva. Saliva is secreted in
the oral phase of swallowing, where it lubricates and moistens foods to facilitate
mastication. Saliva cools hot foods, buffers chemicals, and continuously lavages the oral
cavity. In addition, salivary mucins concentrate on the mucosal surfaces and protect
against desiccation and chemical irritation. Saliva is important in the prevention of dental
caries and has been shown to play an active role in the enamel formation of maturing
teeth by providing a rich supply of inorganic ions (calcium, fluoride, phosphate,
magnesium).
Saliva also contains antibacterial compounds such as lysozyme, secretory IgA, and
salivary peroxidase (thiocyanate-dependent factor). Lysozyme agglutinates bacteria and
activates autolysins. Secretory IgA, the major immunoglobin found in exocrine
secretions, interferes with microorganism adherence. Salivary peroxidase is involved in
the breakdown of salivary thiocyanate, whose breakdown products interfere with
bacterial cell metabolism by oxidizing the enzymes involved in glycolysis. Tenovuo et al.
suggested that salivary flow rate actually is more important in oral hygiene than any of
the antimicrobial factors identified.
Changes in the body's volemic status are reflected in salivary gland secretion.
Hypovolemia causes glandular dehydration and therefore thirst. In addition, mercury,
lead, sulfa, iodine, morphine, antibiotics, and some viruses are actively excreted in saliva;
however, their excretion does not play an important role in homeostasis. Mercury
poisoning can manifest as stomatitis and lead poisoning by the gingival deposition of
lead. The rabies and poliomyelitis viruses are excreted into saliva and can be transmitted
in this manner. Secretory IgA antibodies to the human immunodeficiency virus have also
been isolated from the saliva of infected persons; however, it is unclear whether the virus
is transmissible by this route.
Production of Saliva
Secretory Unit
The production of saliva is an active process that begins proximally in the acinus and is
modified distally by the ducts. The secretory unit refers to the acinus, secretory tubules,
and collecting duct (Fig. 37.7). The acinar cells and proximal ducts are surrounded by
myoepithelial cells that contract to expel preformed secretions from the glandular cells.
The acini secrete saliva, which travels by the intercalated ducts to intra- and interlobular
ducts, which ultimately empty into larger collecting ducts. The intralobular and
interlobular ducts make up the secretory tubules, which are involved in salt and water
transport. As previously described, the parotid and submandibular glands have elaborate
tubuloacinar systems, whereas the sublingual glands have simple systems in which the
interlobular ducts empty into 10 to 12 separate collecting ducts.

FIGURE 37.7. Salivary gland secretory unit. The initial
secretion is formed proximally by the acinar cells and
modified distally to a hypotonic fluid. (From Regizi J,
Batsakis JG. Histogenesis of salivary gland neoplasms.
Otolaryngol Clin North Am 1977;10:298, with
permission.)



Because the parotid gland has only serous acinar cells, it secretes a thin watery saliva,
devoid of mucins. The sublingual gland has only mucous acinar cells and thus produces a
more viscous saliva. The submandibular gland contains acinar cells of both types and
produces a mixed (serous and mucous) saliva. The minor salivary glands contain acini
that are serous, mucous, or mixed.
Secretory Process
Although once thought to be a passive ultrafiltration process, the production of saliva is
now known to be an active process involving cell synthesis and active transport. The
secretion of saliva involves two interrelated processes: primary secretion and ductal
secretion. The primary secretion is produced by the acinar cells and has an electrolyte
composition and osmolality similar to that of plasma. As the secretion moves distally
through the tubule, modifications on the primary secretion are made, producing a
hypotonic fluid.
Histologic examination of the acinar cells reveals marked similarity with other protein-
secreting cells. The secretory (zymogen) granules contain most of the organic
components of the primary secretion. Serous acinar cells produce secretory granules with
amylase, whereas mucous cell granules contain mucin.
Electrochemical studies of acinar cells reveal that active transport of sodium, potassium,
and chloride ions is also involved in production of the primary secretion. Resting acinar
cells show a membrane potential of 20 to 35 mV. Upon stimulation by the autonomic
nervous system, the cells hyperpolarize (become more negative) as a result of the efflux
of K
+
and the influx of Cl. This hyperpolarization, which occurs contrary to other
excitable cells that depolarize upon stimulation, is known as the secretory potential.
As the fluid moves distally, the ducts alter its composition by the secretion of
electrolytes, water, and organic solutes and by the resorption of water and electrolytes.
The degree of modification of the primary secretion by the ducts depends on the rate of
salivary flow. At rapid flow rates, there is little time for secretion and resorption of water
and ions, so the final fluid produced is much like the primary secretion (but always
hypotonic to plasma). At slower flow rates, there is ample time for modification of the
fluid; therefore, the fluid produced is increasingly hypotonic. The net effect of ductal
transport is a decrease in sodium and an increase in potassium concentrations.
Autonomic Innervation
Parasympathetic Nervous System
Stimulation of salivary gland secretion by the PNS produces an abundant watery saliva.
Preganglionic parasympathetic neurons originate in the salivary nuclei of the brainstem,
synapse in autonomic ganglia, and enter the salivary glands by their sensory nerves (Fig.
37.8). The parotid gland receives its PNS innervation from the glossopharyngeal nerve
(cranial nerve IX). The parasympathetic fibers are carried to the otic ganglion by the
lesser superficial petrosal nerve. The postganglionic fibers are then directed toward the
parotid gland by the auriculotemporal nerve (branch of cranial nerve V3). The
submandibular and sublingual glands receive PNS fibers from the chorda tympani nerve
(branch of cranial nerve VII), which travels with the lingual nerve. The fibers synapse at
the submandibular ganglion. Postganglionic parasympathetic fibers release acetylcholine
in close proximity to the glands, and stimulation occurs by way of passive diffusion of
neurotransmitter; that is, no true synapse exists between the postganglionic nerves and
the glands.

FIGURE 37.8. Parasympathetic innervation of the major
salivary glands.



Acetylcholine is the primary neurotransmitter of the PNS. Acetylcholine receptors can be
nicotinic or muscarinic, although only the latter appear to be involved in salivary gland
stimulation. Anticholinesterases, which block the breakdown of acetylcholine, prolong
the action of acetylcholine at the receptor sites and sustain glandular stimulation.
Alternatively, atropine, which competes with acetylcholine for postganglionic receptor
sites, retards glandular stimulation and has been used as a potent antisialagogue. Because
of the bothersome anticholinergic side effects of atropine, scopolamine and
methscopolamine have similarly been used as antisialagogues.
Sympathetic Nervous System
The sympathetic nerve fibers arise in the superior cervical ganglion and travel with the
arteries that supply the salivary glands. The SNS nerves travel with the external carotid
artery to supply the parotid gland, with the lingual artery to supply the submandibular
gland and with the facial artery to the sublingual gland. Norepinephrine is the major
neurotransmitter of the SNS, and all synapses are adrenergic. Stimulation of the gland by
the SNS produces a scant viscous saliva rich in organic and inorganic solutes. Garrett
showed that stimulation of the salivary glands by the PNS produces acinar fluid, whereas
stimulation of the SNS causes the release of preformed organic components. Historically,
the SNS was believed to antagonize the PNS stimulation of salivary secretion, but
Emmelin proved that SNS stimulation actually augments the PNS-stimulated secretion.
Salivary Flow Rates
When the salivary glands are not being stimulated by the autonomic nervous system, they
produce saliva at a rate of approximately 0.001 to 0.2 mL/min per gland. Flow rates can
rise to 0.18 to 1.7 mL/min per gland when stimulated. The 24-hour volume of salivary
secretion has been estimated to be 1,000 to 1,500 mL, or an average flow of 1 mL/min.
Salivary flow in the unstimulated glands is produced primarily by the submandibular
glands (69%), with the parotid and sublingual glands providing 26% and 5% of the flow,
respectively. Once stimulated, the relative contributions of the parotid and submandibular
glands are reversed, with the parotid gland supplying two thirds of the flow. The minor
salivary glands, independent of stimulation, produce about 7% to 8% of the total flow.
Hypersecretion of saliva can be secondary to excessive salivary flow rates (as high as
twice normal) or caused by flow rates that surpass the patient's ability to swallow.
Bilateral tympanic neurectomies (bilateral parasympathetic denervation) have been used
for patients with ptyalism (drooling), with good initial results. Others, however, advocate
bilateral parotid duct rerouting with or without bilateral submandibular gland excision for
long-term management of drooling.
It has been assumed that salivary glands undergo ultrastructural changes during the aging
process that result in hypofunction and xerostomia. Salivary flow rates are independent of
age. Although the acinar cells do undergo a degenerative process, the rate of saliva
production remains constant (2,3). Xerostomia in the elderly is probably the result of
systemic disease or medication side effects. The submandibular glands, which provide
most salivary volume at rest, have been found to be more sensitive to metabolic and
physiologic alterations than the parotid gland (4).
Radiographic Imaging
Although the disease processes that affect the salivary glands are relatively uncommon,
they present a great diversity of pathology. Acute and chronic infections, calculi,
inflammatory diseases, and neoplasms can be imaged to provide important diagnostic
information about the nature and extent of the disease. Appropriate use of plain films,
sialography, and computed tomography has been reviewed recently (5) and is discussed
in detail in Chapter 38.

HIGHLIGHTS
The parotid (Stensen) duct opens intraorally at a papilla
opposite the second upper molar.
The parotid acinar cells are serous cells, and the sublingual
acinar cells are mucous cells. The submandibular acinar cells
are of both serous and mucous types.
The auriculotemporal nerve, a branch of the mandibular (third)
division of cranial nerve V, carries postganglionic
parasympathetic fibers from the otic ganglion to the parotid
gland. Auriculotemporal nerve injury during a parotidectomy
can result in gustatory sweating (Frey syndrome).
The submandibular gland (Wharton) duct opens intra-orally
lateral to the lingual frenulum on the floor of the mouth.
The sublingual gland has approximately 10 small ducts that exit
through the superior aspect of the gland to open intraorally
along the sublingual fold.
The minor salivary glands are composed of mucous, serous, or
mixed cell types, and they have a simple duct system.
Saliva is formed by the salivary gland acinar cells and modified
by the ductal cells into a hypotonic fluid.
The parotid gland receives its PNS fibers from cranial nerve IX.
The fibers travel with the lesser superficial petrosal nerve,
synapse at the otic ganglion, and travel to the gland by way of
the auriculotemporal nerve.
The PNS fibers to the submandibular and sublingual glands
travel with the chorda tympani branch of cranial nerve VII,
which joins the lingual nerve before synapsing at the
submandibular ganglion just adjacent to the glands.
Sympathetic nerve fibers arise in the superior cervical ganglion
and travel with the gland's arterial supply: external carotid
artery to the parotid, lingual artery to the submandibular gland,
and facial artery to the sublingual gland.
CHAPTER REFERENCES
1. Pogrel M, Schmidt B, Ammar A. The relationship of the buccal branch of the facial nerve to the
parotid duct. J Oral Maxillofac Surg 1996;54:71.
2. Ship JA, Nolan NE, Puckett SA. Longitudinal analysis of parotid and submandibular salivary flow
rates in healthy, different aged adults. J Gerontol A Biol Sci Med Sci 1995;50A:M285.
3. Kim SK, Allen ED. Structural and functional changes in salivary glands during aging. Microsc
Res Tech 1994;28:243.
4. Wu AJ, Ship JA. A characterization of major salivary gland flow rates in the presence of
medications and systemic disease. Oral Surg Oral Med Oral Pathol 1993;76:301.
5. Silvers AR, Som PM. Salivary glands. Radiologic Clin North Am 1998;36:941.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

38 SALIVARY GLAND IMAGING
Head & Neck SurgeryOtolaryngology
38




SALIVARY GLAND IMAGING
TERRY S. BECKER

T.S. Becker: Los Angeles CountyUniversity of Southern California Medical Center, Los Angeles,
California.


Diagnostic Imaging Techniques
Plain-Film Radiography
Sialography
Computed Tomography
Magnetic Resonance Imaging
Ultrasonography
Radionuclide Imaging of the Salivary Glands
Angiography
Normal Anatomy
Parotid Gland
Parapharyngeal Space
Submandibular Glands
Sublingual Glands
Inflammatory Disease of the Salivary Glands
Sjgren Syndrome
Chronic Inflammatory Conditions
Sialolithiasis
Lesions of the Parapharyngeal and Masticator Space
Salivary Gland Cysts
Salivary Gland Neoplasms
Benign Neoplasms
Malignant Neoplasms
Chapter References
DIAGNOSTIC IMAGING TECHNIQUES
Imaging techniques available for assessing the salivary glands include plain-film
radiography, sialography computed tomography (CT), magnetic resonance imaging
(MRI), diagnostic ultrasound, and nuclear scintigraphy (1). Each may play a role in
evaluating a patient with pain, swelling, or other symptoms possibly related to salivary
gland disorders (1,2).
Imaging procedures help to differentiate lesions of salivary gland origin from those of the
parapharyngeal space, masticator space, masseter muscle, subcutaneous and deep soft
tissues, mandible, and the submandibular and submental spaces. After localization of the
lesion to the salivary gland, imaging often enables a specific histologic diagnosis to be
made for benign and malignant neoplasms of the parotid, submandibular, and sublingual
glands (3).
Plain-Film Radiography
Before development of more sophisticated imaging techniques, plain-film radiography
was used to determine salivary gland abnormalities. It is still of some value and may
contribute information beyond the physical examination, as in evaluating sialolithiasis.
Although plain films are less sensitive than CT, they are less expensive and more readily
available. Plain-film radiography may also demonstrate calcific and bony lesions that
may mimic salivary gland disease.
The gland should be imaged by multiple views. It is important to attempt to isolate
calcification and overlying calculi from the bony mandible. In viewing the submandibular
(Wharton) duct, additional specialized views of the mouth and submandibular region,
including occlusal views with dental film or anteroposterior views of the mandible with
the chin tilted forward, are also of value. Plain-film examination is useful in evaluating
calculi (Fig. 38.1) or detecting calcification in hemangiomas, lymph nodes, or
pleomorphic adenoma. Calcification in other tumors of the salivary glands is rare.

FIGURE 38.1. Submandibular gland calculus in a 64-
year-old woman with intermittent submandibular
swelling. A: In the plain film, lateral view, a 1-cm
calculus is evident below the angle of the mandible
(arrow). B: The sialogram shows intraglandular ducts
surrounding the calculus (arrow).



Methods of enhancing plain-film radiography and sialography are infrequently of value.
Equipment for xeroradiography is no longer manufactured, but the process provides
excellent contrast resolution. Tomography offers little more information but with
markedly increased radiation exposure. Magnification and subtraction views offer
negligible additional information but deliver increased radiation. The panoramic Panorex
view has been advocated in sialography. It is easily obtained, provides good resolution
and excellent bone detail, and may be valuable for estimating mandibular erosion.
Sialography
Arcelin introduced sialography in 1913, demonstrating a submandibular stone after the
injection of bismuth. Sialography was once the mainstay in diagnosing inflammatory and
neoplastic processes of the salivary glands. Since the advent of CT and MRI, sialography
has played a diminished role. Because of better sensitivity and resolution, CT and MRI
have replaced sialography in the evaluation of salivary gland or adjacent tumor masses.
Although sialography may give some indication about whether a mass is intrinsic or
extrinsic to the gland, its accuracy is inferior to CT or MRI. Sialography is still the most
useful modality to evaluate the intrinsic structure of the salivary ducts (2).
Indications include the suspicion of chronic, recurrent, and nonspecific sialoadenitis;
Sjgren syndrome, Mikulicz syndrome, and other forms of autoimmune disease;
submandibular or parotid gland sialolithiasis; and posttraumatic or postoperative fistula,
stricture, or cyst. Sialography is contraindicated if there is acute infection of the salivary
gland because it may augment the inflammatory process. If subclinical infection is
aggravated after sialography, antibiotic therapy may be required. Although complications
of sialography, including allergic reaction, are rare, the examination is moderately
painful. There is associated discomfort and swelling of the gland, usually subsiding
within 24 to 48 hours. Sialography is performed by injecting an oil-soluble or water-
soluble iodine-containing contrast solution into the Stensen or Wharton duct. Water-
soluble Sinografin is preferred because of the ease of injection (i.e., low viscosity) and
lack of foreign body reaction. Sialography is rarely used for the sublingual glands
because the ducts are numerous and small, opening directly into the floor of the mouth.
Sublingual sialography is only possible if there is an anatomic variation allowing the
catheter to enter the proximal portion of the separate sublingual duct.
Because 75% to 80% of salivary gland calculi are radiopaque, plain films are indicated
before sialography (4). After preliminary plain-film radiography, the Stensen or Wharton
duct is progressively gently dilated. Local anesthesia is unnecessary. A commercially
available sialographic cannula or variant is connected to a contrast-laden syringe and is
inserted into the duct. With the catheter properly positioned, the contrast material is
slowly injected. Fluoroscopy may be useful in observing this filling phase. Although
ductal visualization should always be obtained, acinar filling is unnecessary. Films have
been used during the emptying phase of the gland, but we do not use this technique
routinely.
Certain sialographic features are useful in differentiating intrinsic from extrinsic disease
but are often unreliable. An extrinsic mass tends to displace the gland, and parotid or
submandibular gland parenchyma surrounds the greater portion of an intrinsic mass.
Other features of intrinsic origin are irregular destruction of the gland, punctate
sialectasis, gross enlargement of the gland, and delayed emptying. Irregular contrast
pooling and ductal obstruction and destruction are considered features of malignancy but
are nonspecific, occurring also in benign lesions and inflammatory disease.
Computed Tomography
CT has revolutionized diagnostic imaging since its clinical introduction in the early
1970s. This is especially true for head and neck imaging. Almost universally available,
CT provides precise anatomic detail and is routinely used for identifying and localizing
salivary gland or adjacent tumors. CT is also useful in evaluating salivary gland calculi
and obstructive or inflammatory disease. However, it is inferior to sialography in
studying the ductal system.
CT uses an x-ray tube rotating in a circular fashion around the area of interest. X-rays
produced are imaged by a series of detectors that rotate opposite the x-ray source (i.e.,
third-generation scanner) or by a circle of as many as 1,200 fixed detectors (i.e., fourth-
generation scanner). The cross-sectional anatomy obtained is reconstructed and displayed
as a group of picture elements (i.e., pixels). Using powerful computers, the Hounsfield
units for each pixel can be computed and an image produced by assigning relative
brightness to each pixel. A Hounsfield unit is a unit of x-ray attenuation (i.e., density)
used for CTs, with each pixel assigned a value on a scale on which air is 1,000, water is
0, and compact bone is +1,000. Parotid gland CT density is variable but tends to be
intermediate in density between fat and muscle (Hounsfield value, 20 to +20). Mild
enhancement (approximately 35 Hounsfield units) of the parotid gland occurs after
intravenous contrast infusion. The submandibular glands have less fat than the parotid
glands and therefore are closer to muscle intensity on CT (approximately 40 Hounsfield
units).
CT of the parotid gland is obtained by using thin-section (i.e., 5 mm) axial or
occasionally coronal images, usually after intravenous injection of contrast solution.
Scans are obtained from the external auditory canal to the hyoid bone. Simultaneous
injection of contrast material (i.e., CT sialography) into the ductal system was frequently
performed in the past, but it is rarely needed now because of the higher resolution of
current CT scanners. Because small calcifications of the parotid or submandibular glands
may be obscured, a preliminary noncontrast scan may be obtained (5). Images are filmed
with conventional soft-tissue windows. Additional bone windows are useful for
evaluating calcification, calculi, or bone mass or erosion.
Magnetic Resonance Imaging
MRI uses radiofrequency waves and a strong magnet, most commonly supraconducting,
although resistive and permanent magnets are also available. MRI appears to be
complementary and may be frequently superior to CT (2,6). Soft-tissue resolution and
sensitivity may exceed CT. MRI depends on the water content (i.e., proton density) of
tissue. When the patient is placed in the strong magnetic field of the MRI gantry, nuclear
hydrogen atoms act as small bar magnets, with most atoms aligning parallel to the
magnetic field. A pulsed radiofrequency wave is applied to the field of magnetization,
energy is absorbed by the magnetized hydrogen nuclei, and an electric current is
generated. When the radiofrequency probe is removed, a signal is detected as protons
return to the lower energy state of their original orientation without the magnetic field.
The parameters of nuclear realignment are measured by T1 (i.e., longitudinal) relaxation
time, representing the time required for the nuclei to realign within the external magnetic
field, and by T2 (i.e., transverse) relaxation time, which expresses the dephasing of the
nuclei in a plane transverse to the magnetic field. T1 and T2 effects are demonstrated by
changing the time between radiofrequency pulses (i.e., TR) and varying the time the
signal is measured after the pulse, echo delay time (i.e., TE).
Many improvements in MRI have occurred since its clinical introduction in 1980. Most
of these are related to more effective acquisition sequences (7). Advances have also been
made in surface or local coils, which are placed directly over areas close to the skin
surface, including the parotid gland. The signal-to-noise ratio is improved, and resolution
of the area is better.
MRI may be better than CT in differentiating parotid from parapharyngeal space masses,
such as paraganglioma, schwannoma, or minor salivary gland masses. MRI also appears
to have greater sensitivity and higher resolution than CT. T2-weighted images are
superior to T1-weighted images for differentiating tumor from normal salivary tissue
because most tumors have very high-intensity signals on T2-weighted images (8). Signal
characteristics of MRI are relatively nonspecific, and the complexity of the signal does
not differentiate benign from malignant neoplasms.
MRI is relatively artifact free and does not use ionizing radiation. Multiple planes are
readily obtained without changing the patient position. MRI is less useful in
demonstrating calcification, which is better imaged with CT. MRI is contraindicated for
patients with pacemakers and intracranial ferromagnetic aneurysm clips.
Gadolinium (gadopentetate dimeglumine) is a paramagnetic element frequently used in
MRI, acting as a contrast agent on T1-weighted images. Its role in evaluating salivary
gland lesions is incompletely defined. Although not recommended for routine parotid
imaging, it may have value in selected cases. After administration of gadolinium, the
normal parotid gland is enhanced. The retromandibular vein and the facial nerve may be
identified as structures of low signal intensity. Benign and malignant neoplasms show
various degrees of enhancement. Extraglandular tumor infiltration may be better defined
with gadolinium. The MRI signal (density) of the parotid gland is intermediate between
fat and muscle on T1-weighted images and closer to the density of fat on T2-weighted
images, remaining hyperintense to muscle. The submandibular glands have less fat and
are closer to muscle on T1- and T2-weighted MR images.
Ultrasonography
High-resolution ultrasonography of the parotid or submandibular salivary glands is
occasionally useful for identifying a mass and determining whether it is solid or cystic. A
high-resolution 7.5- to 10.0-MHz transducer is used. Small focal fluid collections, such as
cysts or abscesses, may be identified. Ultrasound-guided fine-needle aspiration is a
simple and inexpensive aid in evaluating lesions too small to identify clinically (9). The
value of ultrasonography in evaluating neoplasms is not well defined, but it can delineate
the relationship of the carotid artery and internal jugular vein to a parotid mass extending
into the parapharyngeal space. Limitations include failure to visualize the entire parotid
gland, relations with the facial nerve, and false-negative findings for small tumors (10).
An aneurysm, which rarely mimics a parotid gland or parapharyngeal space neoplasm,
can be identified with ultrasound. Color-flow Doppler imaging demonstrates that
malignant tumors of the salivary glands are more vascular than benign neoplasms (11).
Although this appears to be an aid in diagnosis, more specificity is yet to be
demonstrated.
Radionuclide Imaging of the Salivary Glands
Radionuclide scanning (i.e., scintigraphy) is used occasionally to evaluate the salivary
glands. Sodium pertechnetate Tc 99m is the most commonly used radioactive
pharmaceutical. The isotope is concentrated and excreted by the salivary glands, which
allows demonstration of uptake in the salivary glands. Because most salivary gland
tumors do not accumulate the radionuclide, a tumor usually appears as a filling defect on
the radionuclide scan. Salivary gland oncocytes in Warthin tumor and oncocytoma
readily take up pertechnetate, resulting in a hot spot. However, because the resolution
of scintigraphy is inferior to that of CT or MRI, radionuclide imaging is not routinely
used.
Gallium 67 citrate is frequently useful for studying inflammatory or neoplastic disease of
the salivary glands and adjacent areas. Because gallium 67 citrate is taken up by dividing
cells, excessive gallium accumulation is observed in inflammatory or neoplastic
processes, including sarcoidosis, melanoma, and lymphoma. Gallium imaging is limited,
however, because of normal minor salivary and secretory gland uptake in the oral and
pharyngeal mucosa. Recently, thallium 201 has been suggested as a replacement for
gallium (12).
Anticarcinoembryonic antigen imaging has a high negative predictive value (100%) in
malignancy of the salivary glands. Scanning using pertechnetate and the patient's
erythrocytes is occasionally useful in the diagnosis of hemangioma. Bone-scanning
agents, such as technetium 99m methylene diphosphonate, may be used to study
subclinical involvement of the mandible or facial skeleton or may detect primary bony
pathology. Bone scanning is especially useful for early detection of disseminated
metastasis. Positron emission tomography, using positron emitting isotopes such as
18
F,
11
C, and
15
O show promise in the imaging of difficult to visualize head and neck
neoplasms.
Angiography
Carotid angiography is important in diagnosing and determining the extent of
parapharyngeal space masses, especially parapharyngeal paraganglioma and
schwannoma. It has less value in evaluating primary parotid masses. Therapeutic
angiography is useful in the preoperative embolization of highly vascular neoplasms,
such as paraganglioma or arteriovenous malformation. Digitation subtraction
angiography with intravenous or intraarterial injection is frequently used to reduce the
radiation dose.
NORMAL ANATOMY
Axial contrast-enhanced CT images are routinely obtained and are best visualized with
soft-tissue windows, using an approximate width/level of 350/50 Hounsfield units (Fig.
38.2). Coronal CT images are occasionally useful but not routinely used because of the
additional time and patient repositioning required. MRI sequences routinely obtained
include axial multiecho (TR/TE = 2,000/40/80) (Fig. 38.3) and coronal T1 (TR/TE =
100/40). Coronal T2-weighted imaging and sagittal T1-weighted imaging are
occasionally useful. If gadolinium-enhanced MRI is desired, additional postcontrast T1-
weighted axial, coronal, and occasionally sagittal sequences are obtained.

FIGURE 38.2. Computed tomography of the normal
parotid and submandibular glands in the axial plane. A:
Line of the mandibular condyle. The parotid gland is
mildly heterogeneous but predominantly reveals a fatty
density. B: Line of the mandibular ramus. The ramus
divides the parotid gland into deep and superficial lobes.
C: Level of the parotid tail. D: Level of the upper
submandibular gland. E: Level of the lower
submandibular gland and hyoid.



FIGURE 38.3. T1-weighted magnetic resonance image
of the normal parotid and submandibular glands. Shown
is the axial plane of the submandibular glands.



Parotid Gland
Largest of the major salivary glands, the parotid is arbitrarily divided into deep and
superficial lobes by the facial nerve. The superficial lobe is identified lateral to the medial
margin of the ramus of the mandible and abuts the posterior aspect of the masseter
muscle, extending anterior and lateral to the masseter muscle. Posteriorly, the superficial
lobe abuts the sternocleidomastoid muscle at the anterior belly of the digastric muscle,
which is identified anteromedially. The tail of the parotid extends inferiorly from the
superficial lobe for a variable distance. The deep lobe extends behind the ramus of the
mandible, bordered medially by the parapharyngeal space, internal carotid artery, and
internal jugular vein and extending to the parapharyngeal space by the stylomandibular
tunnel between the ramus of the mandible and the styloid process.
The facial nerve leaves the skull at the stylomastoid foramen, traveling through a fat pad
and entering the posterior aspect of the parotid gland between the posterior belly of the
digastric and sternocleidomastoid muscle. The fat pad can be identified on CT or MRI.
The intrinsic portion of the facial nerve lies just posterior and lateral to the
retromandibular vein and external carotid artery and divides into major branches
overlying the ramus of the mandible. The facial nerve runs between the deep and
superficial portion of the parotid gland. The facial nerve is not identified on CT but has
been visualized on thin-section MRI (13).
Parapharyngeal Space
The parapharyngeal (or pharyngomaxillary) space is an inverted pyramid-shaped area.
The base of the pyramid is at the base of the skull and the apex is at the level of the hyoid
bone. The tensor veli palatini fascia and tendon divide this space into the prestyloid and
poststyloid compartments. This division corresponds to a line from the medial aspect of
the medial pterygoid plate to the styloid process. The fascia of the medial pterygoid
muscle (anterior) and the fascia of the buccopharyngeal muscle and pharyngeal
constrictors (medial) along with the tensor veli palatini fascia and tendon delimit the
prestyloid parapharyngeal space. This space contains the deep lobe of the parotid gland,
and masses in this space are generally deep lobe parotid neoplasms. The posterior border
of the poststyloid parapharyngeal space is the prevertebral fascia. Included in this space
are the contents of the carotid sheath. Masses in the poststyloid compartment include
paragangliomas, neuromas, and lymphadenopathy.
The masticator space containing the masseter muscle, temporalis muscle, medial and
lateral pterygoid muscle, ramus, and mandibular nerve is separated from the prestyloid
masticator space by a fascial layer extending to the skull base. Salivary gland tumors do
not occur in the masticator space. Benign tumors remain within the compartment of
origin defined by these fascial planes unless there has been prior surgery. Infection or
malignant lesions also breach the fascial planes.
Submandibular Glands
The submandibular glands are identified in the submandibular space (i.e., triangle)
against the submandibular depression on the inner surface of the body of the mandible
posterior and inferior to the mylohyoid muscle, which is separated from the parotid gland
by the stylomandibular fascia. A portion of the gland extends superiorly over the
posterior margin of the mylohyoid muscle. The submandibular gland ductal system drains
by the Wharton duct, which runs between the mylohyoid and hyoglossus muscles,
opening into the mouth adjacent to a small papilla lateral to the frenulum.
Sublingual Glands
The sublingual glands can be visualized with sialography only if their small ducts
coalesce anteriorly into a larger Bartholin duct, which either drains into the floor of the
mouth near the submandibular papilla or into the Warthin duct. Because of their small
size, the sublingual glands are poorly seen on CT, although they do enhance with contrast
administration (2). On T1-weighted MRI, the signal intensity is less than that of fat but
higher than that of muscle (14). These glands decrease in size with age, but, unlike the
parotid gland, the fat content does not appear to change as the patient ages (14).
INFLAMMATORY DISEASE OF THE SALIVARY GLANDS
Sjgren Syndrome
Sjgren syndrome is an autoimmune inflammatory process involving the salivary glands
(most commonly the parotids) and the lacrimal glands. The characteristic triad consists of
dry eyes (i.e., keratoconjunctivitis sicca), dry mouth (i.e., xerostomia), and associated
autoimmune disease, most commonly rheumatoid arthritis. Sjgren syndrome is 10 times
more frequent in women than men, most often affecting middle-aged or older persons.
Although many imaging modalities have been used, parotid sialography remains the most
effective imaging procedure for diagnosing Sjgren syndrome and determining the extent
of disease. Involvement tends to be bilateral. The parotid gland is mild to markedly
enlarged. In the early stage, multiple punctate contrast collections are observed
throughout the gland (Fig. 38.4). As the disease progresses, the punctate contrast
collections become larger and more globular. Ultimately, the parotid may become
completely replaced by circular contrast collections, resulting in a cavitary mass with
complete destruction of the salivary gland. Areas of tubular sialectasia or strictures may
also occur. Delayed films demonstrate variable retention of contrast material, which often
remains for long periods of time, particularly if oil-based contrast agents are used.

FIGURE 38.4. Sjgren syndrome in a 38-year-old
woman with a nontender parotid swelling. The sialogram
shows multiple small collections of contrast within the
parotid gland, and the punctate nature suggests early
disease.



The CT appearance of Sjgren syndrome is that of bilateral parotid and less frequently
submandibular gland enlargement with multiple areas of low attenuation (Fig. 38.5).
Complications, including cyst formation with lymphoid infiltration (i.e.,
pseudolymphoma), are readily visualized. Multiple cysts as large as 4 mm and
multiseptate cystic masses as large as 3 cm in diameter have been demonstrated in
Sjgren syndrome with ultrasound. As the disease progresses, increased fat in the glands
becomes apparent on both CT and MRI (15). Imaging of enlarged glands in this disease is
important due to the high incidence of non-Hodgkin lymphoma. In such patients, an
intraglandular mass is evident.

FIGURE 38.5. Sjgren syndrome in a 49-year-old
woman. Computed tomography shows that the parotid
glands are bilaterally diffusely enlarged and markedly
heterogeneous in density, with a suggestion of multiple
small lucencies.



Chronic Inflammatory Conditions
Imaging procedures may be useful in cases of chronic, recurrent, or intermittent
sialadenitis in which the infectious agent is unknown. This is particularly true in the
assessment of sialolithiasis. Although usually nonspecific, sialography or CT may
demonstrate inflammatory masses or more specific infections of the salivary glands, such
as tuberculosis, syphilis, actino-mycosis, or animal-scratch fever.
With extensive or recurrent sialadenitis, abnormalities of the ductal system are best
demonstrated by sialography (Fig. 38.6). These abnormalities include sialectasia of the
main or intraglandular ducts, stricture, and filling defects within the ducts related to
debris, fibrosis, or inflammatory infiltrate. Sialography cannot differentiate tubular
sialectasis of recurrent sialadenitis, the punctate to globular contrast collections, or
recurrent parotitis of children with Sjgren syndrome. In these cases, the diagnosis must
be based on clinical history, serologic testing, or lip biopsy.

FIGURE 38.6. Chronic sialadenitis with sialectasia in an
84-year-old woman. The sialogram reveals dilatation of
the major branches of the Stensen duct (arrow). Several
smaller normal ductal branches are also visualized
(arrowheads).



Sialography is contraindicated in acute sialadenitis because inflammatory disease may be
amplified. However, CT or MRI demonstrates the fluctuant, enlarged, variably enhancing
salivary gland and extraparotid inflammation involving the masseter muscle,
subcutaneous soft tissues, and masticator or parapharyngeal spaces. Edema involving the
salivary gland or extraglandular soft tissues increases the T2-weighted signal.
Abscess formation (Fig. 38.7) most commonly occurs within the parotid gland or less
frequently in masticator or parapharyngeal spaces. The abscess cavity is visualized on CT
as a hypointense central region surrounded by a variably enhancing rim. The MRI
appearance is that of a central water-density collection (i.e., low or medium signal
intensity on T1-weighted images, with increased signal intensity on T2-weighted images)
in a bed of edema. Ultrasonography is valuable and cost effective in the diagnosis of
abscess. A focal fluid collection is manifested by a hypoechoic or anechoic mass with
increased through transmission. Ultrasound is also used to localize the abscess for
aspiration drainage.

FIGURE 38.7. Parotid abscess with sialectasia in a 52-
year-old man with intermittent swelling. A: Computed
tomography shows multiple low-density masses in the
swollen superficial lobe. B: Sialogram reveals multiple,
large, globular contrast collections, consistent with
sialectasia. C: Ultrasound shows lucent anechoic masses,
confirming fluid within the gland. Aspiration was
performed under ultrasound guidance.



Sialolithiasis
The search for and evaluation of sialolithiasis is greatly aided by several diagnostic
imaging procedures. Plain-film radiography is useful in the diagnosis of sialolithiasis,
although it is not as sensitive as CT. As many as 20% of calculi in the submandibular and
20% to 40% of calculi in the parotid gland are not visible on plain-film examinations.
Sialography reveals intraductal calculi as ductal filling defects and is superior to plain
films in detecting radiolucent calculi. Sialography best demonstrates associated
sialodochitis and sialectasia. High-resolution MR sialography has been introduced. Using
a heavily T2-weighted, two-dimensional, fast spin-echo technique with a surface coil, the
parotid and submandibular ducts are well visualized. Combined with plain-film
radiography to enhance detection of calculi, this technique may prove to be a noninvasive
replacement for conventional sialography (16).
Lesions of the Parapharyngeal and Masticator Space
CT frequently differentiates parapharyngeal from intrinsic parotid lesions. The
demonstration of a fat plane separating the normal parotid gland from the mass indicates
parapharyngeal location. Lack of the fat plane implies a deep lobe parotid tumor. This
distinction can be difficult if the tumor is pedunculated, having only a small attachment
to the gland.
CT and MRI are useful in differentiating prestyloid and poststyloid lesions (17). The fat
in the parapharyngeal space helps the radiologist distinguish masses arising in the
prestyloid compartment of the parapharyngeal space from masses in the poststyloid
compartment. A poststyloid lesion displaces the parapharyngeal fat anteriolaterally,
whereas a prestyloid lesion pushes the fat medially. A lesion localized in the prestyloid
space is a salivary gland neoplasm and may extend anterior to the styloid passing through
the stylomandibular tunnel. A poststyloid compartment mass is probably a schwannoma
or paraganglioma but may be retropharyngeal lymphadenopathy (e.g., metastatic disease)
or less frequently meningioma, hemangioma, chondrosarcoma, rhabdomyosarcoma, or
perineural metastasis.
Lesions in the masticator space lying lateral to the medial pterygoid fascia are probably
masses arising from the masticator space, such as meningioma, neurolemma, sarcoma,
squamous cell carcinoma, dentigerous cyst, or masseteric hypertrophy. No salivary gland
lesions are found in the masticator space. Four findings indicate masticator space origin:
location anterior and lateral to the parapharyngeal fat, limitation of tumor by boundaries
of the masticator space (i.e., the sphenoid bone, posterior aspect of the mandible, and
zygomatic arch), obliteration of the fat planes within the masticator space, and a tendency
to spread through the foramen ovale.
MRI has been used in the diagnosis of parapharyngeal space lesions, such as glomus
tumors (i.e., paragangliomas), neuromas, and minor salivary gland tumors. Internal artery
displacement helps in differentiating these lesions (18). Primary salivary gland tumors
(most commonly deep lobe pleomorphic adenoma) and minor salivary gland neoplasms
displace the internal carotid artery. Displacement occurs because deep lobe parotid
lesions extend from the stylomandibular tunnel into the parapharyngeal space and minor
salivary gland tumors arise from salivary gland rests in the prestyloid compartment of the
parapharyngeal space or from minor salivary glands of the parapharyngeal mucosa.
Because schwannomas arise from the vagus nerve, which is posterior to the internal
carotid artery, these masses tend to displace the internal carotid artery anteriorly.
Paragangliomas arise from the posterior compartment of the parapharyngeal space, with
anterior displacement of the internal carotid artery. The MRI signal characteristics of
these lesions are similar: a well-circumscribed lesion with intermediate signal on T1
weighting and increasing signal on T2 weighting. Focal areas of necrosis, hemorrhage, or
calcifications may alter this appearance. Paragangliomas may be quite vascular and
demonstrate characteristic signal flow voids, resulting in a salt and pepper appearance.
Salivary Gland Cysts
Cysts of the salivary glands may be classified as congenital or acquired. Congenital forms
include branchial cleft, dermoid, and epidermoid cysts. Type 2 branchial cleft cysts,
which contain a lining of squamous or ciliated epithelium, may occur in the parotid
gland. Dermoid or epidermoid cysts are of congenital origin. Although these may exist at
birth, they are slow growing and generally not identified until adulthood. Acquired cysts
may be posttraumatic (e.g., sialocele), lymphepithelial, or retention cysts (mucocele,
ranula).
The imaging appearance of most cysts is similar. Sialography demonstrates displacement
of the ductal system around the nonspecific mass. Rarely, communication of contrast
occurs within the cyst. CT demonstrates a well-circumscribed low-density mass
(Hounsfield value, 0 to 20) consistent with the water content of the cyst fluid. If there has
been infection, the central density may be higher and an enhancing variable-thickness
wall may be evident on postcontrast infusion scans. The MRI appearance is consistent
with the water content of the cyst, with a lower intensity signal on T1-weighted
sequences, increasing intensity on intermediately weighted scans, and a very bright signal
on T2-weighted sequences. Signal characteristics may be altered if there has been
previous infection or hemorrhage.
Benign lymphoepithelial cysts presenting with painless swelling of the parotid glands
have recently been described in human immunodeficiency virus-positive patients (19,20)
(Fig. 38.8). Patients may or may not have the clinical signs of acquired
immunodeficiency syndrome. CT or MRI demonstrates multiple, bilateral, well-
circumscribed, endoparotid masses. An enhancing rim may be evident on CT. The MRI
appearance resembles water-density cysts of other causes, with a low-intensity signal on
T1-weighted images and an increased signal on T2-weighted images. The patients usually
have associated cervical lymphadenopathy.

FIGURE 38.8. Computed tomography reveals
lymphoepithelial cysts in a 40-year-old man with
acquired immunodeficiency syndrome. A: Multiple low-
density lesions (arrow) are evident in the tail of the left
parotid gland. B: Several small upper jugular chain
lymph nodes (arrowheads) are associated.



The sialocele (Fig. 38.9) is a posttraumatic cyst of the parotid or submandibular glands,
resulting from laceration or stricture with rupture of Stensen or Wharton duct. The
resultant extravasated mucinous or serous fluid accumulates within the gland or extends
around the duct. The sialocele is also called a pseudocyst because no true epithelial lining
exists. Sialocele may result from blunt trauma, faulty dentures, buccal mucosal
ulcerations, surgical sutures, or calculus removal.

FIGURE 38.9. Sialogram of a traumatic sialocele in a
54-year-old man after an altercation. A facial laceration
was sutured. The wound later began to bulge and 10 mL
of saliva was aspirated. A: Tangential view. A large
contrast collection fills from the main Stensen duct
(arrow). B: Oblique view. The contrast collection erupts
from the main Stensen duct near the ampulla. The normal
parotid gland (arrow) is seen posteriorly.



Fistula formation is usually the result of a lacerating injury. The fistula may communicate
with the oral cavity, oropharynx, or hypopharynx or extend through the skin with an
external opening. Fistulae are best demonstrated with sialography. Contrast draining into
the pharynx or onto the skin may be evident. If the fistula opening is adequately
visualized, injected contrast can demonstrate the tract and filling of the salivary gland.
Ranula (retention cyst, mucocele) results from obstruction of a sublingual or minor
salivary gland duct in the floor of the mouth. It may be confined to the floor of the mouth
above the mylohyoid muscle or may extend below the hyoid muscle (plunging, deep, or
diving ranula).
SALIVARY GLAND NEOPLASMS
Although salivary gland neoplasms constitute fewer than 3% of all malignancies, the
diagnosis is readily suspected clinically. The patient usually presents with a progressively
enlarging painless mass in the region of the parotid or submandibular gland. Pain or
facial paralysis may suggest malignancy. Although sialography can indicate the size and
position of the neoplasm, CT and MRI are the procedures of choice for diagnosing and
determining the extent of disease (21).
Benign tumors of the parotid gland usually have well-defined margins; some have
capsules. The appearance of these lesions is similar on CT and MRI. Enhancement varies,
but it is generally not prominent. Low-grade malignant lesions, such as mucoepidermoid
carcinoma, may be difficult to differentiate from benign lesions. Malignant lesions cannot
be differentiated from benign lesions based on the CT density, CT enhancement, MRI
signal, or postgadolinium MRI enhancement. However, infiltration of the soft tissues,
masseter muscle, or parapharyngeal space or tumor extension along the course of the
parapharyngeal or facial nerves (frequently with adenoid cystic carcinoma) suggests
malignancy.
MRI may be superior to CT in demonstrating the well-defined margins and internal
architecture of benign neoplasms of minor salivary glands (22). Positron emission
tomography holds some promise for differentiating between malignant and benign
lesions. Ultrasound and CT have been useful in guiding fine-needle aspiration of salivary
lesions, particularly small lesions and lesions in the parapharyngeal space. The recent
development of open interventional MRI units allows MRI-guided needle aspiration of
many difficult to access lesions, including salivary lesions in the parapharyngeal space
(23).
Benign Neoplasms
Pleomorphic Adenoma
Pleomorphic adenoma (benign mixed tumor) accounts for approximately 60% to 70% of
all benign tumors of the salivary glands. Pleomorphic adenoma occurs most commonly in
the parotid gland and to a lesser extent in the submandibular gland and minor salivary
glands. Sublingual pleomorphic adenoma is rare.
The sialographic appearance of pleomorphic adenoma is identical to other benign
intraparotid neoplasms. There is smooth displacement of the salivary gland ducts and
contrast-laden parenchyma. There is no abrupt truncation, focal irregularity, or
extravasation of contrast material.
The CT appearance of pleomorphic adenoma is that of a well-circumscribed mass with
homogeneous or heterogeneous density (24) (Fig. 38.10). The density is higher than that
of normal serous fluid and fat-containing parotid parenchyma. Because fluid, fat,
hemorrhage, or dystrophic calcification may exist in pleomorphic adenoma, a
heterogeneous appearance is common. Contrast enhancement varies but tends to be mild.
CT sialography demonstrates displacement of the contrast-laden parenchyma by the
filling defect of the tumor. Because of the improved resolution of current CT scanners,
CT sialography is rarely used.

FIGURE 38.10. Pleomorphic adenoma of the right
parotid in a 17-year-old girl with a nontender mass. A:
Computed tomography (CT) shows a well-circumscribed
low-density mass in the superficial lobe. B: The T1-
weighted axial magnetic resonance (MR) image reveals a
low-signal mass that corresponds well with the CT image.
C: The intermediate-weighted MR image demonstrates
the increased signal of the mass. D: T2-weighted coronal
MR image shows the well-circumscribed mass with a bright signal. A high-intensity
signal reflects the high proton content of the mass but is not specific.



MRI demonstrates a predominantly heterogeneous well-circumscribed mass of
intermediate to low signal intensity on T1-weighted images and increased signal on T2-
weighted sequences (Fig. 38.10). Hemorrhage is revealed as areas of high-intensity signal
on T1- and T2-weighted images. Calcification is usually not evident on MRI.
Warthin Tumor and Oncocytoma
Warthin tumor (adenolymphoma or papillary cystadenoma lymphomatosum) accounts for
fewer than 10% of parotid tumors. These tumors are invariably benign and occur only in
the parotid gland. They contain oncocytic, cystic, and lymphatic components and may
represent heterotopic salivary gland epithelial tissue trapped within intraparotid lymph
nodes.
The sialographic appearance of Warthin tumor is identical to pleomorphic adenomas and
other benign tumors of the parotid gland. The CT appearance of Warthin tumor (Fig.
38.11) is that of a homogeneous well-circumscribed mass in the parotid gland, frequently
exhibiting hypodense or cystic areas. Calcification does not occur. The MRI appearance
is that of a homogeneous well-circumscribed mass with intermediate to low signal
intensity on T1-weighted images and increased signal on T2-weighted images. Warthin
tumor is bilateral in approximately 10% of the patients, and differentiation from
lymphadenop-athy, bilateral cysts, or the less frequent bilateral form of pleomorphic
adenoma may be difficult.

FIGURE 38.11. Computed tomography of Warthin
tumor. A: A large well-defined mass involves the
superficial lobe of the left parotid gland. The mass
enhances diffusely. B: At the level of the parotid tail,
areas of lower density (arrowheads) are consistent with
cystic components observed in the posterior aspect of the
mass.



Oncocytoma (Fig. 38.12), a benign tumor related to Warthin tumor but composed entirely
of oncocytes, is a rare lesion, constituting fewer than 1% of all salivary gland tumors.
Both oncocytoma and Warthin tumor are unique in that they accumulate technetium-99m
pertechnetate.

FIGURE 38.12. Magnetic resonance imaging of an
oncocytoma in the right parotid tail. A: Coronal T1-
weighted scan shows a bilobed relatively low-intensity
signal (arrows) describing a mass that attaches to the
inferior aspect of the right parotid gland. An extrinsic
mass can mimic this appearance. B: Axial T2-weighted
scan shows a moderately increased signal of the mass.
Notice the submandibular gland (S). (Courtesy of Dr.
Irving L. White, Long Beach, CA.)



Hemangioma and Lymphangioma
Hemangiomas and lymphangiomas are benign nonepithelial tumors of the salivary
glands, almost always involving the parotid. Hemangiomas and lymphangiomas are
composed of a network of epithelial-lined capillaries or lymphatic spaces, respectively.
Dilated vascular channels may be identified. Hemangiomas are seen as well-
circumscribed benign-appearing lesions that displace the parotid ductal system on
sialography. Plain-film examination or CT may demonstrate the calcification of multiple
phleboliths within the tumor. The CT appearance of hemangioma is that of a well-defined
heterogeneous-density mass. Because the tumor may involve the surrounding
musculature or parapharyngeal space, it may mimic a malignant lesion. Hemangioma has
a heterogeneous signal on T1- and T2-weighted MR images. Areas of signal void may be
caused by blood flow within the tumor.
Lipoma and Liposarcoma
Lipomas are rare lesions of the parotid gland and may be intraparotid or paraparotid. The
characteristic CT appearance is that of low attenuation related to fatty tissue (Hounsfield
value, 50 to 150). Lipoma in the submandibular space or paraparotid region may blend
with the normal fat.
The MRI appearance of lipoma is related to the fat within the tumor. A well-
circumscribed mass with a high-intensity signal on T1-weighted images demonstrates an
intermediate signal on T2-weighted sequences. It is not possible to differentiate a lipoma
from a liposarcoma based on signal characteristics. A heterogeneous signal may be
displayed for a lipoma with fibrosis or for a liposarcoma with hemorrhage and necrosis.
Malignant Neoplasms
Mucoepidermoid Carcinoma
Mucoepidermoid carcinoma is the most common salivary gland malignancy, accounting
for approximately 10% of salivary gland neoplasms. Tumor aggressiveness correlates
with the clinical course. Low-grade mucoepidermoid carcinoma has CT and MRI
characteristics resembling benign lesions, appearing well circumscribed and regularly
marginated without infiltration into the adjacent soft tissues. A homogeneous to
heterogeneous density is demonstrated on CT. Low to intermediate signal intensity is
exhibited on T1-weighted images, and the signal intensity increases on T2-weighted
images.
The more aggressive or cellular mucoepidermoid carcinoma has a more irregular
appearance on CT, with irregular margination and infiltration into the soft tissues.
Heterogeneous CT density may occur but is not a reliable sign of aggressiveness. The
MRI appearance of high-grade mucoepidermoid carcinoma reflects the greater cellularity
and lower water content of the lesion. The signal is intermediate on T1- and T2-weighted
sequences.
Adenoid Cystic Carcinoma
Adenoid cystic carcinoma (Fig. 38.13) accounts for 30% of minor salivary gland tumors,
approximately 15% of submandibular gland tumors, and 2% to 6% of parotid gland
neoplasms. Adenoid cystic carcinoma has a slow but prolonged course with frequent
recurrences. Perineural extension, although seen in squamous cell carcinoma and other
malignancies, is most common in adenoid cystic carcinoma, allowing tumors to spread
through the parapharyngeal space or intracranially. CT signs of perineural extension
include obliteration of the normal fat plane beneath the stylomastoid foramen and tumor
enhancement along the course of the facial nerve, with resultant facial paralysis.

FIGURE 38.13. Computed tomography of a recurrent
adenoid cystic carcinoma in a 49-year-old woman who
had previous right submandibular gland resection. There
is an irregularly infiltrating enhancing mass in the floor of
the mouth and parapharyngeal space. Anterior fatty
infiltration indicates hypoglossal nerve invasion.



Noninfiltrating adenoid cystic carcinoma within the parotid or submandibular glands is
radiographically indistinguishable from other neoplasms. Tumors in the minor salivary
glands demonstrate diffuse vascular enhancement with variable infiltration into the
adjacent soft tissues. Recurrent adenoid cystic carcinoma is disclosed by CT
enhancement and increased signal on T2-weighted images, which may occur along the
course of the facial or parapharyngeal nerves. Intracranial extension may be better
demonstrated on MRI than CT.
Squamous Cell Carcinoma
Squamous cell carcinoma of the salivary gland occurs most commonly in the parotid
gland and is usually the result of metastasis. Primary squamous cell carcinoma may be
quite aggressive, but CTs and MR images are nonspecific. Low-grade tumors resemble
benign or other low-grade malignancies. Characteristic loss of margination, irregularity,
and soft-tissue infiltration may be identified in aggressive tumors.
Malignant Variations of Pleomorphic Adenoma
Both CT and MRI may demonstrate the progressive nature of carcinoma ex pleomorphic
adenoma and malignant mixed tumor if they are infiltrative. However, they are usually
indistinguishable from other neoplasms of the parotid gland. If dystrophic calcification
exists, CT may offer an advantage over MRI, although tumor definition may be better on
MRI. The rare benign metastasizing pleomorphic adenoma must be differentiated from
recurrent pleomorphic adenoma, which may take many years to develop, or multicentric
pleomorphic adenoma, which accounts for approximately 0.5% of tumors.
Metastasis
Most metastases to the parotid or submandibular gland are from continuous spread of
squamous cell carcinoma of the pharynx or neck. Hematogenous metastases have been
described in carcinoma of the breast, neck, lung, and kidney and in metastatic melanoma.
Despite the vascularity of the parotid gland, bloodborne metastasis is rare.
Lymphoma
Salivary gland lymphoma is almost always the result of systemic lymphoma, producing
intraparotid, paraparotid, and submandibular triangle lymphadenopathy that displaces the
submandibular gland. Intrinsic submandibular gland lymph-adenopathy is rare.
The characteristic CT appearance of lymphoma is that of multiple, well-circumscribed,
homogeneous masses within the parotid gland and in the paraparotid region that may
enhance slightly with contrast (1). Lymphadenopathy should also be sought in the
submandibular, submental, and internal jugular spaces. The MRI appearance is that of a
homogeneous intermediate-intensity signal on T1-weighted sequences. A variable but
increased signal is identified on T2-weighted images. The CT and MRI appearances are
altered if there is necrosis.
Inflammatory hyperplastic lymphadenopathy resembles lymphomatous lymphadenopathy
on CTs. Diffuse infiltration of the subcutaneous soft tissues or periparotid region may
give a clue to the inflammatory nature. The T2-weighted images may demonstrate a
brighter signal for inflammatory lymphadenopathy than for lymphoma, but it is usually
impossible to differentiate inflammatory from neoplastic lymphadenopathy on MRI
(Table 38.1).

TABLE 38.1. IMAGING PROCEDURES




HIGHLIGHTS
CT and MRI are the most frequently used imaging techniques
for evaluating salivary gland disease.
Plain-film radiography is of limited value but may demonstrate
salivary gland calculi. However, CT is more sensitive.
Sialography is recommended for primary evaluation of the
ductal system. Sialography is no longer used for evaluating
tumor masses.
Ultrasonography, radionuclide imaging, and angiography have
less important but occasionally useful roles in evaluating
salivary gland disease.
Sjgren syndrome is best imaged by sialography. Punctate to
globular contrast collections progressing to complete
destruction of the parotid gland may be identified.
Chronic inflammatory conditions of the salivary glands that
may lead to sialectasia, stricture, or fistula are best evaluated by
sialography. Fibrosis, edema, and abscess formation are best
visualized by CT or MRI.
CT or MRI is useful in differentiating primary parotid masses
from tumors of the parapharyngeal space and in defining
intrinsic lesions of the salivary glands.
The CT appearance of pleomorphic adenoma is that of a well-
circumscribed mass with variable density. The tumor
demonstrates a heterogeneous, intermediate, or low signal on
T1-weighted images, with an increased signal on the T2-
weighted image. Other benign neoplasms, including Warthin
tumor and oncocytoma, may have a similar appearance.
Mucoepidermoid carcinoma is the most common malignancy of
the salivary glands. If aggressive, irregular margination and
soft-tissue infiltration are radiographically identified. However,
mucoepidermoid carcinoma, adenoid cystic carcinoma,
squamous cell carcinoma, and malignant variations of
pleomorphic adenoma are usually nonspecific and frequently
resemble benign neoplasms.
CHAPTER REFERENCES
1. Silvers AR, Som PM. Salivary glands. Radiol Clin North Am 1998;36:941965.
2. Weissman JL. Imaging of the salivary glands. Semin Ultrasound CT MR 1995;16:546568.
3. Kassel EE. CT sialography, part I: introduction, technique, anatomy and variants. J Otolaryngol
1982;12[Suppl]:110.
4. Rabinov K, Weber A. Radiology of the salivary glands. Boston: GK Hall, 1985.
5. Stone DN, Mancuso AA, Rice D, et al. Parotid CT sialography. Radiology 1981;138:393397.
6. Casselman JW, Mancuso AA. Major salivary gland masses: comparison of MR imaging and CT.
Radiology 1987;165:183189.
7. Chaudhuri R, Bingham JB, Crossman JE, et al. Magnetic resonance imaging of the parotid gland
using the stir sequence. Clin Otolaryngol 1992;17:211217.
8. Rice DH, Becker T. Magnetic resonance imaging of the salivary glands. Arch Otolaryngol Head
Neck Surg 1987;113:7880.
9. Feld R, Nazarian L, Needleman L, et al. Clinical impact of sonographically guided biopsy of
salivary gland masses and surrounding lymph nodes. ENT J 1999;78:905912.
10. Bruneton JN. Ultrasound in salivary gland disease. ORL J Otorhinolaryngol Relat Spec
1993;55:284289.
11. Martinoli C, Derchi LE, Solbiati L, et al. Color Doppler sonography of salivary glands. AJR Am J
Roentgenol 1994;163:933941.
12. Arbab AS, Kolzumi K, Hiraike S, et al. Will thalium-201 replace gallium-67 in salivary gland
scintigraphy? J Nucl Med 1996;37:18191823.
13. Teresi LM, Lufkin RB, Wortham DG, et al. Parotid masses: MR imaging. Radiology
1987;163:405409.
14. Sumi M, Izumi M, Yonetsu K, et al. Sublingual gland: MR features of normal and diseased states.
AJR Am J Roentgenol 1999;172:717722.
15. Izumi M, Eguchi K, Nakamura H, et al. Premature fat deposition in the salivary glands associated
with Sjgren syndrome: MR and CT evidence. AJNR Am J Neuroradiol 1997;18:951958.
16. Varghese JC, Thornton F, Lacy BC, et al. A prospective comparative study of MR sialography and
conventional sialography of salivary duct disease. AJR Am J Roentgenol 1999;173:14971503.
17. Curtin HD. Separation of the masticator space from the parapharyngeal space. Radiology
1987;163:195204.
18. Som PM, Sacher M, Stollman AL, et al. Common tumors of the parapharyngeal space: refined
imaging diagnosis. Radiology 1988;169:8185.
19. Holliday RA, Cohen WA, Schinella RA, et al. Benign lymphoepithelial parotid cysts and
hyperplastic cervical adenopathy in AIDS-risk patients: a new CT appearance. Radiology
1988;168:439441.
20. Kirshenbaum KJ, Nadimpalli SR, Friedman M, et al. Benign lymphoepithelial parotid tumors in
AIDS patients: CT and MR findings in nine cases. AJR Am J Roentgenol 1991;12:271274.
21. Som PM, Biller HF. High-grade malignancies of the parotid gland: identification with MR
imaging. Radiology 1989;173:823.
22. Kaneda T, Minami M, Ozawa K, et al. Imaging tumors of the salivary glands. Oral Surg Oral Med
Oral Pathol 1994;77:385390.
23. Davis SP, Anand VK, Dhillon G. Magnetic resonance navigation for head and neck lesions.
Laryngoscope 1999;109:862867.
24. Som PM, Shugar JMA, Sacher M, et al. Benign and malignant parotid pleomorphic adenomas: CT
and MR studies. J Comput Assist Tomogr 1988;12:6569.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

39 NONNEOPLASTIC DISEASES OF THE SALIVARY GLANDS
Head & Neck SurgeryOtolaryngology
39




NONNEOPLASTIC DISEASES OF THE SALIVARY
GLANDS
DALE H. RICE

D.H. Rice: Department of OtolaryngologyHead and Neck Surgery, University of Southern California,
Los Angeles, California.


Acute Inflammatory Lesions
Mumps
Other Viral Diseases
Acute Suppurative Sialadenitis
Chronic Inflammatory Disorders
Granulomatous Diseases
Primary Tuberculosis of the Salivary Glands
Animal-Scratch Disease
Sarcoidosis
Sjgren Syndrome
Sialolithiasis
Cystic Lesions
Radiation Injury
Trauma
Sialadenosis
Other Disorders
Complications
Chapter References
Nonneoplastic salivary gland disorders encompass a wide variety of different diseases.
These include acute and chronic inflammatory disorders, granulomatous diseases,
Sjgren syndrome, sialolithiasis, and other entities. A more general classification would
divide these disorders into inflammatory and noninflammatory lesions. In either case,
they represent a heterogeneous group of diseases that can afflict the major or minor
salivary glands but are much more common in the major glands. In general, the history
and physical examination allow easy differentiation of the lesions into their appropriate
classification. Additional studies may be needed to make a final specific diagnosis or to
help with treatment, but extensive testing is rarely necessary. The subject should be
approached systematically.
ACUTE INFLAMMATORY LESIONS
Mumps
The most common viral disorder involving the salivary gland is mumps, which is also the
most common cause of parotid swelling. This phenomenon will change with the
increasing use of the mumps vaccine and may largely disappear in industrialized
countries over time. Peak incidence of mumps occurs in children aged 4 to 6 years. The
onset is generally characterized by pain and swelling in one or both parotid glands after
an incubation period of 2 to 3 weeks. Fever, malaise, myalgia, and headache may precede
the onset of parotid swelling. The diagnosis is made by demonstrating antibodies to the
mumps S and V antigens and to the hemagglutination antigen. Studies have shown that
more than 95% of adults have neutralizing antibodies (1). However, many cases are
subclinical. The diagnosis of mumps may also be made by isolating the virus from urine;
this can be done up to 6 days before and 13 days after the salivary gland symptoms
appear. Major complications are uncommon but include sudden deafness, pancreatitis,
meningitis, and orchitis. Islet cell antibodies have been reported, and a recent
epidemiologic study showed a significant association between mumps and the subsequent
rapid onset of childhood diabetes (2). Chronic obstructive sialadenitis may develop many
years after the acute episode of mumps. In addition, the submandibular and sublingual
glands may be involved, but less commonly.
Other Viral Diseases
Cytomegalovirus may also involve the salivary glands (in salivary gland inclusion
disease). It involves newborns and may lead to mental and physical retardation and
hepatosplenomegaly, jaundice, and thrombocytopenic purpura. Other viral agents that
may affect the salivary glands include coxsackievirus A, echoviruses, influenza A, and
the lymphocytic choriomeningitis virus. Treatment for all viral infections is symptomatic.
Acute Suppurative Sialadenitis
Acute suppurative sialadenitis was first reported in 1828 (3). Most cases involve the
parotid gland, but some also occur in the submandibular gland. The increased parotid
susceptibility is due to the lessened bacteriostatic activity of the parotid saliva when
compared with submandibular saliva. The high-molecular-weight glycoprotein and sialic
acid content in the mucinous saliva has a greater bacterial aggregating ability than does
serous saliva (4). In addition, mucoid saliva has a higher concentration of lysozymes and
IgA. Acute suppurative sialadenitis accounts for 0.03% of hospital admissions in the
United States, with 30% to 40% of these occurring in the postoperative patient (5). The
disease typically begins on the third to fifth postoperative day, with the highest incidence
after gastrointestinal procedures. It occurs in approximately 1 in 1,000 to 2,000 operative
procedures. Patients in the sixth and seventh decades of life are most frequently affected,
with an equal sex distribution.
Salivary stasis is believed to be the precipitating event, probably from either obstruction
or decreased production. Predisposing conditions in the outpatient setting include calculi
or duct stricture. Many commonly used classes of medications cause a relative
dehydration. In the postoperative patient, the predisposing conditions most often
implicated are dehydration and poor oral hygiene. These are often combined with
reduced resistance in the patient exposed to hospital flora. Furthermore, if the patient is
not eating, the stimulatory effect of mastication on the salivary glands is lost, as is the
detergent action of food itself.
The classic presentation of acute suppurative sialadenitis is the sudden onset of diffuse
enlargement of the involved gland with associated induration and tenderness. Purulent
saliva can be seen at the duct orifice, particularly with massage of the gland. The saliva
should be cultured for both aerobic and anaerobic bacteria and a specimen for Gram
staining obtained. Organisms usually involved include coagulase-positive Staphylococcus
aureus, with other aerobic organisms occasionally implicated, particularly Streptococcus
pneumoniae, Escherichia coli, and Haemophilus influenzae (6). The most common
anaerobic organisms are Bacteroides melaninogenicus and Streptococcus micros (7).
Twenty percent are bilateral. Histologic examination shows glandular destruction with
abscess formation. There is erosion of the ducts with penetration of the exudate into the
parenchyma.
Initial treatment should include adequate hydration, improved oral hygiene, repeated
massage of the gland, and intravenous antibiotics. Empiric administration of a
penicillinase-resistant antistaphylococcal antibiotic should be started while awaiting
culture results. Quoted mortality rates approach 20% (8). Much of this mortality is
probably secondary to the underlying illness that the patient had before the onset of
parotitis, because the mortality was zero in a report of the disease in the noncritically ill
patient (9). My personal experience does substantiate this. Impressive improvement is
expected within the first 24 to 48 hours. If this does not occur, incision and drainage
should be considered. Ultrasound or computed tomography (CT) evaluation will show if
abscess formation has occurred. This is best done by elevating a standard parotidectomy
flap and then using a hemostat to make multiple openings into the gland, spreading in the
general direction of the facial nerve. A drain is then placed over the gland and the wound
closed. In some cases, it is possible to perform CT-guided or ultrasonography-guided
needle aspiration of parotid abscesses, which may help avoid an open operative
procedure. It is well to bear in mind that fluctuation of the parotid gland does not occur
until very late in the course of the disease because of the multiple investments of fascia
within the gland. Thus, it is impossible to determine the presence of early abscess
formation on the basis of physical examination alone.
CHRONIC INFLAMMATORY DISORDERS
A key etiologic event in chronic sialadenitis is thought to be a lowered secretion rate with
subsequent salivary stasis. Like acute sialadenitis, chronic sialadenitis is more common in
the parotid gland than in other locations. A few patients with chronic recurrent
sialadenitis seem to represent progression from the recurrent parotitis of childhood (10).
Most represent permanent damage to the gland from acute suppurative infection. Over
time, the disease leads to sialectasis, ductal ectasia, and progressive acinar destruction
combined with a lymphocytic infiltrate. Histologically, it is impossible to differentiate the
subtypes of chronic salivary inflammation because the salivary glands have a similar
tissue response in all these cases. The sialographic appearance parallels the degree of
histologic change.
Changes in saliva occur as a result of the chronic inflammatory process. During acute
episodes, the sodium and chloride values approach those in serum (11). Glucose is also
elevated, and phosphate is decreased. Increases also occur in IgA, IgG, IgM, albumin,
and transferrin, which leak from plasma and myeloperoxidase, lactoferrin, and lysozyme
produced by the inflammatory infiltrate or the acini. In this setting, IgG dominates the
immunoglobulins, reflecting the serum pattern rather than the typical salivary pattern in
which IgA dominates. In chronic sialadenitis, between acute episodes, increased salivary
sodium and protein values remain whereas they are normal in noninflammatory
enlargements (12).
In patients with chronic sialadenitis, there is usually a history of mildly painful recurrent
parotid enlargement that is often aggravated by eating. The physical examination
confirms this enlargement, and massage of the gland may produce scanty saliva at the
duct orifice. In fact, a permanent xerostomia develops in 80% of these patients. In the
initial workup, the clinician should look for treatable predisposing factors such as a
calculus or a stricture. If no treatable etiology is found, initial management should be
conservative and includes the use of sialagogues, massage, and antibiotics during acute
exacerbations. Conservative measures usually suffice, but if they fail, more aggressive
treatment options are periodic ductal dilation, ligation of the duct, total gland irradiation,
tympanic neurectomy, and excision of the gland. Only the last option works uniformly
(13).
It may be possible to accomplish atrophy of the parotid gland by occlusion of the ductal
system with a protein solution (14). Recurrent parotitis may also involve children from
infancy to age 12 years, but it is a somewhat different disease. Unlike the adult form, this
disease affects males more than females. The disease usually begins with a sudden onset
of either unilateral or bilateral parotid swelling with no obvious underlying cause.
Clinically, the child is generally not ill, but the salivary chemistries are altered as in the
adult form. Mild pain may be present, but xerostomia is not (15). The disease may
disappear at puberty or continue into adulthood.
Chronic recurrent parotitis may eventually lead to the development of the benign
lymphoepithelial lesion (16). This lesion belongs in the spectrum of diseases
characterized by a lymphoreticular infiltrate combined with acinar atrophy and ductal
metaplasia. The ductal metaplasia ends in the development of the so-called
epimyoepithelial island (17). The benign lymphoepithelial lesion generally affects a
single gland; there is a small female predominance (Fig. 39.1). The lesion is usually first
noticed as an asymptomatic enlargement unless there is associated infection. In the
absence of complications, no active treatment is usually needed. If intermittent infections
occur, each should be treated as acute sialadenitis. If the lesion becomes cosmetically
unacceptable, excision may be necessary.

FIGURE 39.1. Sialogram of patient with benign
lymphoepithelial lesion.



The benign lymphoepithelial lesion should be followed carefully. As of 1985, there had
been significant reports of the evolution of this disease into more aggressive entities,
including 84 cases of a lymphoproliferative disease, 29 cases of carcinoma, and 12 cases
of pseudolymphoma. The lymphoproliferative disorders are usually histiocytic or
lymphocytic lymphomas involving extrasalivary sites. The development of a frank
lymphoma may be heralded by the onset of hypogammaglobulinemia or leukopenia.
Carcinomas have generally been salivary and most commonly undifferentiated. The
possibility that they may develop should be appreciated. Many of the reported cases have
involved patients of Native American or Eskimo extraction, although this may merely
represent reporting artifact (18).
GRANULOMATOUS DISEASES
Primary Tuberculosis of the Salivary Glands
Primary salivary tuberculosis is common. The parotid gland is more frequently involved
than the others, and the disease is usually unilateral. Most cases of primary tuberculosis
of the salivary glands are believed to arise from a focus of infection in the tonsils or teeth.
It occurs in one of two formsan acute inflammatory lesion or a chronic tumorous
lesion. The inflammatory lesion presents a difficult diagnostic problem because it may
mimic the more common acute inflammatory diseases; often the diagnosis is not made
until an acid-fast salivary stain and a purified protein derivative skin test are performed.
A purified protein derivative test may be unreliable, because infections caused by the
atypical mycobacteria are increasing in relation to Mycobacterium tuberculosis and often
produce a negative skin test (19,20). After the diagnosis is correctly made, the treatment
is the same as for any acute tuberculosis infection. With the current increasing use of
fine-needle aspiration cytology, the tumorous lesion can often be diagnosed before
excision, which then may not be necessary. However, if the disease is caused by a
mycobacterium resistant to the usual drugs, excision will be curative. Secondary
tuberculosis may also occur but tends to involve the submandibular or sublingual glands
more frequently than the parotid and is associated with pulmonary tuberculosis.
Animal-Scratch Disease
Animal-scratch disease does not involve the salivary glands directly but frequently
involves periparotid lymph nodes and may involve the parotid by contiguous spread. The
causative agent of this disease has been identified but not classified. It is a gram-negative
bacillus sensitive to gentamycin (21,22). The disease is self-limiting, and treatment is
symptomatic but probably now should include gentamycin. Actinomycosis may also
occur in the salivary glands. Treatment involves incision and drainage combined with
long-term penicillin therapy as with actinomycosis elsewhere in the head and neck.
Introduction of the bacteria is usually from the tonsils or teeth.
Sarcoidosis
Sarcoidosis is a granulomatous disease of unknown etiology; diagnosis is reached by
exclusion. Clinically, manifest salivary gland involvement occurs in only 6% of cases,
but in histologic studies, involvement can be demonstrated in up to 33% of cases (23).
Uveoparotid fever (Heerfordt syndrome) is a particular form of sarcoidosis characterized
by uveitis, parotid enlargement, and facial paralysis. It most frequently occurs in the third
to fourth decades of life. Initial symptoms include a prodrome with fever, malaise,
weakness, nausea, and night sweats lasting several days to several weeks. Uveoparotid
fever may occur with or without the other systemic manifestations of sarcoidosis.
Submandibular, sublingual, and lacrimal involvement may also appear; the swelling lasts
months to years without suppuration and with eventual resolution. Involvement of the
minor salivary glands may occur, and labial or palate biopsy may establish the diagnosis
(24). The treatment is symptomatic, with corticosteroids being most useful in the acute
phase, particularly for facial paralysis. However, even without treatment, facial paralysis
is usually transient. The uveitis should be followed closely, because it can lead to
glaucoma.
SJGREN SYNDROME
Sjgren syndrome is characterized by a lymphocyte-mediated destruction of the exocrine
glands leading to xerostomia and keratoconjunctivitis sicca (Fig. 39.2 and Fig. 39.3). It is
the second most common autoimmune disease after rheumatoid arthritis (25). Ninety
percent of cases occur in adult women, but the disease may occasionally occur in children
(26). The average age at onset is 50 years. The clinical manifestations were first
described by Hadden in 1888 (27). Four years later, Mikulicz published a single case
report of a patient with bilateral lacrimal, parotid, and submandibular gland swelling (28).
In 1925, Gougerot described this as a distinct clinical entity. In 1933, however, Sjgren, a
Swedish ophthalmologist, published a classic monograph on the disease and emphasized
its systemic nature (29). Sjgren syndrome is now classified into two forms. Primary
Sjgren involves the exocrine glands only, whereas secondary Sjgren syndrome is
associated with a definable autoimmune disease, most commonly rheumatoid arthritis
(30). Primary Sjgren may involve up to 3% of the population. The disease usually has
an indolent course, and a variety of nonspecific symptoms may precede the ability to
make the diagnosis by 5 to 10 years. Symptoms of Sjgren syndrome include burning
oral discomfort and a sandy sensation in the eye. The xerostomia increases the risk of
caries. In 80% of primary and 30% to 40% of secondary cases, unilateral or bilateral
salivary gland swelling occurs, usually of the parotid gland. The swelling may be either
intermittent or permanent. Arthritis is the most common complaint in secondary Sjgren
syndrome. There are genetic differences among patients with primary and secondary
Sjgren syndrome. Among the numerous other potential symptoms are interstitial
pneumonitis, dryness of the skin, Raynaud phenomenon, achlorhydria,
hepatosplenomegaly, genital dryness, hyposthenuria, myositis, and pancreatitis.
Neuropsychiatric dysfunction is common. Patients with primary Sjgren syndrome have
a greater incidence of recurrent parotitis, Raynaud phenomenon, purpura,
lymphadenopathy, myositis, and renal involvement than do those with secondary Sjgren
syndrome. In patients with primary Sjgren syndrome, 75% show evidence of respiratory
involvement, usually a diffuse interstitial disease or small airway disease (31).

FIGURE 39.2. Sjgren syndrome in patient with
acquired immunodeficiency syndrome-related complex.



FIGURE 39.3. Computed tomography of a patient with
Sjgren syndrome showing stippled calcification.



A variety of laboratory findings suggests that one of the underlying defects in Sjgren
syndrome is B-cell hyperactivity with or without abnormalities of immunoregulation.
This is manifested by a polyclonal hypergammaglobulinemia, numerous autoimmune
antibodies, and circulating IgG immune complexes (32,33). Between 70% and 90% of
patients demonstrate rheumatoid factor, whereas 55% to 70% demonstrate antinuclear
antibodies. Smaller numbers may demonstrate salivary duct antibody, partial cell
antibody, thyroglobulin antibody, and thyroid microsomal antibody.
Two relatively specific autoantibodies are those to Ro (SSA) and La (SSB). One or the
other of these is detected in 40% to 60% of patients with primary Sjgren syndrome.
Very sensitive techniques such as ELISA will detect them in up to 95% but will also find
them in 10% to 15% of healthy control subjects. Diagnosis often requires a biopsy of
either the labial mucosal glands or of the parotid. One looks for aggregates of 50 or more
lymphocytes and plasma cells.
In 1986, a conference was held in Copenhagen on Sjgren syndrome, where diagnostic
criteria for primary and secondary forms were established. A more recent prospective
multicenter study led to a screening questionnaire and new set of diagnostic criteria with
good discrimination between patients and control subjects (34). Although classified as an
autoimmune disease, to date there are no convincing data demonstrating that autoantigens
participate in the tissue damage. There is probably a genetic predisposition especially
involving histocompatibility complex antigens HLA-DR3, -DRw52, and -DR2 (35).
SIALOLITHIASIS
Eighty percent of salivary calculi occur in the submandibular gland, whereas less than
20% occur in the parotid and approximately 1% in the sublingual gland. Minor salivary
gland calculi are uncommon, with a predilection for the upper lip and buccal mucosa
(36). In 75% of calculi involving the major glands, only one single calculus has been
found. Multiple gland involvement occurs in approximately 3%, and there is a slight male
preponderance, with most occurring in middle age. Calculi commonly occur in patients
with chronic sialadenitis but are otherwise only infrequently associated with other
diseases. Gout is the only systemic disease known to cause salivary gland calculi. Calculi
in gout are composed of uric acid, whereas most calculi otherwise are largely calcium
phosphate with small amounts of magnesium, ammonium, and carbonate. A mixture of
carbohydrates and amino acids form the organic matrix of these calculi. Despite their
similar chemical makeup, 90% of submandibular calculi are radiopaque, whereas 90% of
parotid calculi are radio-lucent with standard facial x-rays. Essentially all are detectable
with CT. Ultrasonography is underutilized in this country. In Europe it is widely
available, relatively inexpensive, and accurate in trained hands. Magnetic resonance
imaging will not detect calculi. However, in time, improvements in magnetic resonance
sialography may allow the detection of stones.
A probable prerequisite for calculus formation is the presence of a nidus of material
allowing the precipitation of salts, almost certainly coupled with salivary stasis. The
submandibular duct is believed to be more susceptible to calculus formation because its
saliva is more alkaline and has a higher concentration of calcium and phosphate and a
higher mucus content. Furthermore, the duct is longer and has an antigravity flow.
Submandibular calculi usually arise within the duct, whereas those in the parotid are at
the hilum or within the parenchyma.
Most patients present with a history of recurrent swelling and pain in the involved glands,
often associated with eating. Infections may or may not occur with repeated episodes of
obstruction and swelling. Occasionally, calculi are discovered incidentally, and
occasionally they appear as acute suppurative sialadenitis. The calculus may be palpable
in the involved duct, and the gland may be diffusely enlarged and mildly tender. Massage
of the gland demonstrates decreased flow of a cloudy or mucopurulent saliva. Plain x-ray
films frequently reveal submandibular calculi but much less so for parotid. Sialography is
essentially 100% effective in making the diagnosis. Ultrasound and CT are also excellent
for detecting calculi (Fig. 39.4 and Fig. 39.5).

FIGURE 39.4. Plain radiograph showing large
submandibular calculus.



FIGURE 39.5. Computed tomography showing parotid
calculus.



Complications of sialolithiasis include acute suppurative sialadenitis, ductal ectasia, and
stricture. Treatment depends on the location of the calculus. Those at or near the orifice
of the duct may be removed transorally, whereas those within the hilum of the gland
often require complete excision of the gland. Newer treatments such as lithotripsy and
transductal removal are on the horizon. With simple removal of the stone, the recurrence
rate is approximately 18%, because the underlying cause, which is probably unknown,
will not have been corrected (37).
Occasionally, a calcified phlebolith may be mistaken radio-graphically for an
asymptomatic salivary calculus. However, several things help to differentiate them.
Phleboliths are generally circular, laminated, and multiple. In addition, on sialography,
they lie outside the ductal system (38).
CYSTIC LESIONS
Most true cysts of salivary tissue occur in the parotid gland, where they account for 2% to
5% of all parotid lesions. Cysts may be acquired or congenital. A type of congenital cyst
is the dermoid cyst, which consists of keratinizing squamous epithelium with associated
skin appendages, and is treated by complete removal with preservation of the facial
nerve. A congenital ductal cyst that is generally manifest in infancy requires sialography
for diagnosis and no therapy unless repeated infections occur (39). The first arch
branchial cleft cysts account for less than 1% of all branchial cleft anomalies (Fig. 39.6
and Fig. 39.7). They are classified as type 1 and type 2 cysts. Type 1 is an ectodermal
lesion of the first arch only. Type 2 is an ectodermal and mesodermal lesion involving the
first and second arches (40). Type 1 cysts are a duplication anomaly of the membranous
external auditory canal, whereas type 2 cysts are a duplication anomaly of the
membranous and cartilaginous external auditory canal. Regardless of the type and
location of the cyst, the tract of the cyst is intimately associated with the facial nerve.
Furthermore, frequent prior infections may obscure the true nature of the lesion, with
many patients having repeated incision and draining before the correct diagnosis being
made. Excision during a quiescent period with preservation of the facial nerve is curative.

FIGURE 39.6. Patient with first branchial cleft cyst.



FIGURE 39.7. Computed tomography of a patient with
first branchial cleft cyst.



Acquired cysts may be associated with neoplasms, the benign lymphoepithelial lesion,
trauma, parotitis, calculi, duct obstruction, mucus extravasation, and human
immunodeficiency virus (HIV) infection (41). The neoplasms most frequently associated
with cysts are pleomorphic adenoma, adenoid cystic carcinoma, mucoepidermoid
carcinoma, and Warthin tumor. Nonneoplastic cysts that are asymptomatic do not need to
be treated, whereas those that become repeatedly infected should be excised.
Mucoceles and mucous cysts almost invariably involve the minor salivary glands, most
commonly on the lips, buccal mucosa, and ventral portion of the tongue. Mucous cysts
are true cysts with epithelial lining and result from duct obstruction. Mucoceles, however,
do not possess an epithelial lining and are not true cysts but represent mucus
extravasation into the surrounding soft tissues. If required, treatment of both is by
excision or marsupialization. The ranula is a retention cyst of the sublingual gland, and
the so-called plunging ranula extends from the floor of the mouth into the neck. The
treatment is excision.
RADIATION INJURY
Low-dose radiation to a salivary gland causes an acute tender and painful swelling. The
serous cells in the acini are exquisitely sensitive and exhibit marked degranulation and
disruption. This causes pools of zymogen granules to appear in the acini. In addition, an
acute inflammatory reaction causes a purulent exudate within the ducts and the
parenchyma. On the other hand, mucous cells and acini and the epithelial cells of the
intercalated and intralobular ducts exhibit little histologic change. The acute
inflammatory reaction subsides without treatment provided that the irradiation is stopped.
Continued irradiation leads to complete destruction of the serous acini and subsequent
atrophy in the gland. Radiation-induced thyroid neoplasms are well documented, and
there is similar evidence that salivary and parathyroid tumors are also induced. Both
pleomorphic adenomas and malignant neoplasms are increased in incidence (42,43). A
recent study has implicated dental x-rays in this country.
TRAUMA
Penetrating injuries to the parotid glands may involve the duct or the facial nerve. Any
penetrating injury posterior to the anterior border of the masseter muscle should be
suspected of causing a ductal injury. Inspection of the wound directly often allows
adequate assessment of the duct. If the duct cannot be identified, a probe may be passed
transorally and located in the wound. This should confirm the status of the duct. If the
duct has been transected, optimum treatment is end-to-end anastomosis over a
polyurethane catheter with 9-0 sutures. The catheter is then sutured in place to the buccal
mucosa to be removed in 2 weeks. If the proximal end of the duct cannot be readily
identified, compression of the gland often produces enough saliva from the cut end to
allow its identification. Alternately, if the primary duct is long enough, it may be sutured
directly into the oral cavity through a puncture wound. If this is not possible, the duct
may be ligated or a new duct may be created from buccal mucosa. In all these situations,
repeated dilation with lacrimal probes may be necessary to achieve a satisfactory final
result.
Laceration of the parenchyma can usually be managed conservatively. Closing the
parenchyma and the capsule with a few interrupted sutures generally suffices. If a
salivary cutaneous fistula develops, healing can generally be ensured by repeated
aspiration and a pressure dressing. Resolution may take 1 to 2 weeks to allow for the
traumatized ductal system to reopen. Persistence of a fistula strongly suggests duct
obstruction rather than parenchymal injury alone (44). In this setting, sialography should
be performed. If duct obstruction is found, repair should be performed, if possible. If
conservative treatment fails, excision of the gland is curative and administration of
enough radiation to destroy the gland. The latter is probably ill advised in the younger
patient.
Injury to the facial nerve may also occur from penetrating wounds. A thorough evaluation
of facial nerve function should be performed on any patient suffering a penetrating injury
to the face. If the patient cannot perform volitional testing, the Hilger nerve stimulator
may be used. If the wound is anterior to a vertical line from the lateral canthus to the
mental foramen, repair is probably unnecessary (even with clear dysfunction) because
recovery is likely.
Injuries posterior to this line should be repaired immediately. Whereas delayed repair has
some possible theoretic advantages, these advantages are overshadowed by the
importance of being able to find both ends of the nerve and the ability to do so through
the open wound itself. Additionally, some believe that delayed repair does not really have
advantages. Repair must be meticulous and with magnification.
Blunt trauma may also injure the gland with resultant contusion, edema, or hemorrhage.
These usually resolve without treatment, although temporary duct obstruction may occur.
A large hematoma should be drained before it becomes organized because subsequent
fibrosis and scarring may lead to duct obstruction and to a cosmetic deformity.
The submandibular and sublingual glands are managed in a similar manner to that of the
parotid gland, but ductal injuries here are much less common because of the protection
afforded by the mandible.
SIALADENOSIS
Sialadenosis is a nonspecific term used to describe a noninflammatory nonneoplastic
enlargement of a salivary gland, usually the parotid. In most cases, the mechanism is
unknown, and there are many associations. The salivary gland enlargement is generally
asymptomatic. Bilateral parotid gland swelling is common in obesity secondary to fatty
hypertrophy. However, a complete endocrinologic and metabolic workup should be
performed before this diagnosis can be made. This is important because obesity is
frequently associated with other disorders such as diabetes mellitus, hypertension,
hyperlipidemia, and menopause.
Malnutrition is also commonly associated with sialadenosis. This can occur in the form of
pellagra, cirrhosis, diabetes mellitus, beriberi, anorexia nervosa, and bulimia.
Sialadenosis has been reported in kwashiorkor and hypovitaminosis A. In these
conditions, the enlargement is secondary to acinar hypertrophy.
Parotid swelling is intimately associated with alcoholic cirrhosis. It is so rare in
nonalcoholic cirrhosis that it can be used as a differential diagnostic feature, occurring in
30% to 80% of cases of alcoholic cirrhosis. Evidence suggests that this enlargement is
based on protein deficiency, and histologic changes are similar to those in general
malnutrition.
Any disease that interferes with the absorption of nutrients may also lead to parotid gland
hypertrophy. Reported diseases include celiac diseases, bacillary dysentery, carcinoma of
the esophagus, Chagas disease, and ancylostomiasis. Sialadenosis may also occur in
uremia, hypothyroidism, myxedema, testicular or ovarian atrophy, pregnancy, lactation,
and chronic relapsing pancreatitis.
The prognosis is generally good if the underlying disease can be corrected. In this setting,
the parotid glands generally return to normal.
OTHER DISORDERS
Pneumoparotitis may occur with any episode of increased intrabuccal pressure. It has
been reported in glass blowers and after intubation and endoscopy. It has also been
reported as an idiopathic event, and I have seen one patient who could inflate the parotid
gland at will. Cheilitis glandularis is an uncommon disease manifested by enlargement of
the labial salivary glands, which then secrete a clear, thick, sticky mucus (45). The
glandular hypertrophy may occur to such a degree that eversion of the lower lip occurs, in
which case vermilionectomy is usually curative. In Kussmaul disease (sialodochitis
fibrinosa), a mucous plug obstructs a collecting duct. This commonly occurs in a
dehydrated patient and is manifested by recurrent swelling with associated pain. The
appearance of a mucous plug at the duct orifice is diagnostic. Treatment consists of
gentle massage and sialagogues to extrude the plug in addition to rehydration when
appropriate. A number of drugs may cause salivary gland enlargement as a side effect.
These include isoproterenol, ethambutol, phenobutazone, phenothiazine, iodine
compounds, and heavy metals.
Necrotizing sialometaplasia is a disease of cryptogenic origin, although some cases
appear to occur as a reaction to injury. It is generally manifested as a mucosal ulceration
most commonly found in the hard palate, but it may occur in any salivary tissue. There is
a male preponderance. Necrotizing sialometaplasia may be mistaken histologically for
squamous cell or mucoepidermoid carcinoma, and this is the importance of this disease.
Mucosal ulceration with pseudoepitheliomatous hyperplasia, ischemic lobular necrosis,
and dissolution of acinar walls with a release of mucus occur. This causes a subsequent
inflammatory granulation tissue response combined with squamous metaplasia of the
acini and ducts. The lesion is always self-healing and requires no treatment. If the
diagnosis is in doubt, a biopsy should be performed (46).
A disease that may be a variant has recently been described. It has been termed subacute
necrotizing sialadenitis, and 15 cases have been reported as of 1995. The lesion presents
as a painful, nonulcerated, erythematous swelling of the posterior hard palate.
Histologically, most of the acinar cells are lost, and there is atrophy or necrosis of the
ductal cells. The lesion is self-healing in 2 to 4 weeks (47).
Aberrant salivary gland tissue may occur in a variety of locations. It is particularly
common within lymph nodes in the parotid area. It has also been reported to occur in the
mandible, lower neck, hypopharynx, middle ear, sternoclavicular joint, thyroglossal duct,
and pituitary gland. In the mandible, the tissue may be on the surface or in a central
location. If on the surface, the lesion appears to be merely ectopic submandibular tissue
and is always benign. Central lesions are uncommon and even less common in the
maxilla. When these tissues become neoplastic, the type of tumor may be a
mucoepidermoid carcinoma, adenoid cystic carcinoma, or adenocarcinoma, in that order
(48).
Finally, parotid gland enlargement may occur in patients with HIV infection. It usually
occurs as a symmetric diffuse enlargement of both parotid glands with or without
involvement of the submandibular glands. This clinical presentation in a young person
should raise suspicion of HIV infection. Table 39.1 summarizes the diagnosis and
management of salivary gland diseases.

TABLE 39.1. DIAGNOSIS AND
MANAGEMENTDISEASES OF THE SALIVARY
GLAND



COMPLICATIONS
Complications of nonneoplastic diseases of the salivary glands may be the result of the
salivary gland process itself or an indirect result of another condition. For example, viral
diseases affecting the salivary glands rarely lead to a complication related to the salivary
glands but may cause serious injury, either temporary or permanent, to other organ
systems. In contrast, acute suppurative sialadenitis may more directly lead to serious
illness. Depending on the bacteria involved and the severity of the illness, the patient is
susceptible to septicemia or spread of the infection locally into the deep neck spaces.
The chronic salivary gland diseases may lead to no sequelae or may severely affect the
salivary tissue, leading to xerostomia. The benign lymphoepithelial lesion is associated
with the development of lymphoma, pseudolymphoma, and anaplastic carcinoma.
Sarcoidosis may be associated with facial paralysis and with severe systemic illness.
Sjgren syndrome may manifest itself only with xerostomia, but it may also be associated
with other more serious collagen vascular diseases such as rheumatoid arthritis and
systemic lupus erythematosus.
Sialolithiasis, which may be due to acute suppurative sialadenitis, may lead to the
development of more severe neck infections and to septicemia. The same may occur with
first branchial cleft cysts. Finally, penetrating injuries may lead to the development of
salivary cutaneous fistulae or to partial or total facial paralysis (Table 39.2).

TABLE 39.2. POSSIBLE COMPLICATIONS
SALIVARY GLAND DISEASES




HIGHLIGHTS
Acute inflammatory lesions can usually be diagnosed on the
basis of the history and physical examination alone.
Chronic inflammatory diseases usually cannot be diagnosed
reliably without further investigation such as x-ray films and
biopsy.
For an exact diagnosis, granulomatous diseases, like chronic
inflammatory diseases, generally require investigation beyond
the history and physical examination.
Depending on the location of the calculus, sialolithiasis may be
managed by transoral excision or resection of the entire gland.
Cysts require a thorough workup to evaluate the cause and to
allow proper management planning.
Penetrating trauma should be carefully evaluated to assess
injury to the ductal system or important adjacent or related
structures.
Sialadenosis should be investigated thoroughly to determine the
underlying cause.
Ulcerating lesions of the palatal mucosa should be carefully
investigated to avoid confusing necrotizing sialo-metaplasia
with carcinoma.
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15. Rankow RM, Polayes IM. Diseases of the salivary glands. Philadelphia: W.B. Saunders, 1976.
16. Batsakis JG, Sylvest V. Pathology of the salivary glands. Chicago: American Society of Clinical
Pathologists, 1977.
17. Batsakis JG, Bernacki EG, Rice DH, et al. Malignancy and the benign epithelial lesion.
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18. Nagao K, Matsuzki O, Siaga H, et al. A histopathologic study of benign and malignant
lymphoepithelial lesion of the parotid gland. Cancer 1983;52:1044.
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20. Long ML, Jafek BW. Cervical mycobacterial disease. Trans Am Acad Ophthalmol Otol
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

40 CONTROVERSIES IN SALIVARY GLAND DISEASE
Head & Neck SurgeryOtolaryngology
40




CONTROVERSIES IN SALIVARY GLAND DISEASE
JOHN M. TRUELSON

J.M. Truelson: Department of Head and Neck Oncology, University of Texas Southwestern Medical
Center at Dallas, Dallas, Texas.


Gustatory Sweating
Diagnosis
Prevention
Treatment
Parotid Cysts
Xerostomia
Parotid Surgery
Preoperative Evaluation
Nerve Dissection
Intraoperative Facial Nerve Monitoring
Benign Mixed Tumors
Imaging
Chapter References
Controversies surrounding the diagnosis and management of salivary gland masses often
involve the limits of our technology. The primary controversy often lies not in how to
treat a given disease but by what means the diagnosis can be established without doubt.
Alternatively, many times new treatments or diagnostic modalities arise that may
supplant the older and more established methods. There may be little difficulty in
accepting the new ideas due to a clear superiority. More often, however there are many
pros and cons to each side of the question.
GUSTATORY SWEATING
Postparotidectomy regrowth of parasympathetic nerves, originally innervating the parotid
gland, frequently causes reinnervation of the interrupted sympathetic fibers of sweat
glands and blood vessels in the facial skin. The resulting facial flushing and gustatory
sweating (GS) is a common occurrence after parotid surgeryso much so that it should
probably be considered a sequela rather than a complication. A recent study showed that
after 1 year 43% of patients were symptomatic and 96% had a positive starch iodide test
over a mean area of 18 cm
2
. Fortunately, only 5% to 10% had severe symptoms (1).
Diagnosis
Minor's starch iodide method has been the traditional evaluation for confirming the
presence of GS (2). Wada and Takagaki (3) described a similar method primarily used for
parts of the body other than the face. Both methods involve the stimulation of sweat after
application of starch powder to the face, but neither is quantitative. Newer methods allow
some degree of quantification by measuring sweat. Eisele (4) described application of
tissue paper to the face, which is wetted only in the affected area after a sialogogue is
administered. Isogai and Kamiishi (5) similarly created a stencil of blotting paper over
the parotid region. The paper is weighed before and after stimulation and sweating for a
quantitative measurement. Another method uses iodine-sublimated office paper, which
changes color when wet, quantitating sweat by digitizing the stencil (6). Infrared
thermography provides indirect measurements of sweat and vascular flushing by
measuring a biphasic skin temperature response after a gustatory stimulus. Initially, the
skin temperature increases due to vascular flushing and later decreases due to sweating.
This method seems to be less cumbersome than the others, because it is a quantitative
measurement of temperature and does not necessitate dealing with templates. It may be
an even better method of measurement, because it is the only method that demonstrates
the physiologic response of vasodilatation. All these tests are useful in the measurement
of sweating, so that the question of controversy raised is not as much which test to use
but rather when to use them. These tests are used in research to quantitate the
effectiveness of new treatments, but a patient that is bothered by the sweating has no
interest in the number of grams of sweat, the temperature measurement, or the make up
of the sweat. In the clinical setting, it may be helpful to document that GS is in fact
present before treatments that may have potential side effects, such as further surgery or
botulinum toxin (described below). If the patient has only minimal symptoms, then there
is no need for testing outside of a study situation.
Prevention
The prevention of Frey syndrome would be far preferable to treating the problem, and
various surgical methods have been described. A limited resection has been advocated as
a method for decreasing the incidence of GS (7,8 and 9). The rational for this method is
that because resection of the parotid causes GS, resection of less parotid may decrease
GS. Two authors describe removing a deep lobe tumor, replacing the retracted superficial
lobe (8,9). This has the added benefit of improved cosmesis but would have a limited
application because few tumors would easily lend themselves to such a technique.
Dulguerov et al. (10) evaluated various implants, placed in the parotid bed at the time of
parotidectomy, in 46 patients, compared with 24 patients without implants. By clinical
evaluation, 11 of 24 patients (53%) with no implant had Frey syndrome, compared with 1
of 46 (2%) with implants. Objective tests were positive in 76% (16/21) without implants
and 20% (8/39) with implants. The implants also may improve cosmesis, although some
had an increased incidence of salivary fistula.
A temporoparietal flap (11) has been transposed immediately after parotidectomy, which
has the advantages of being autologous tissue in the operative field and is cosmetically
acceptable. The superficial temporal artery must be preserved to use this option. A
sternocleidomastoid flap (12) has also been described but may require a lower incision
and has the potential of leaving a defect in the neck.
All these surgical methods have decreased the rates of GS. When limiting the resection,
there is potential for inadequate margins, as discussed in a later section of this chapter.
For neoplasms, especially malignant ones, postoperative tumor surveillance is essential.
Physical examination may be less accurate when flaps or implants are placed, but
magnetic resonance imaging (MRI) and/or computed tomography (CT) combined with
fine-needle aspiration may outweigh the need for palpation. The head and neck surgeon
must balance the need for reconstruction and prevention of GS with the potential effect
on tumor surveillance by physical examination.
Treatment
Although the occurrence is common, the treatment of GS can be difficult. Various
treatments have been used by symptomatic GS patients, such as antiperspirants and
scopolamine. Unfortunately, these have only temporary effects and require repeated
application. Botulinum toxin has recently been shown to be effective (13) because it
binds to presynaptic cholinergic nerve terminals, which prevents release of acetylcholine,
effectively paralyzing the innervated muscle. In this application, the proposed mechanism
of action is blockage of acetylcholine release at the nerve terminals that have mistakenly
reinnervated sweat glands. Laskawi et al. (13) demonstrated complete cessation of GS in
19 patients (22 treated sides) within 2 days, with no side effects noted. GS reappeared in
12 patients, but the mean duration of the effect was 17.3 months. Laccourreye et al. (14)
confirmed control of Frey syndrome in 53% of patients (17/30) with an initial injection of
Botox. Recurrent patients were successfully managed by reinjection. Adverse effects,
such as temporary paresis of the upper lip and upper lids, were partial (15). Botulinum
injection is the first nonoperative treatment that seems to have promise of being a
successful long-term treatment. Although reported results are all less than 2 years, a large
number seem to have lasting results. Even if reinjection is necessary, the long lasting
effect of botulinum makes the treatment tolerable.
PAROTID CYSTS
Cystic lesions of the parotid may be true cysts, lymphoepithelial cyst, mucoceles,
keratomas, or branchial cysts (16). These lesions are indistinguishable from neoplasms on
physical examination, but CT usually shows a fluid-filled mass that is diagnostic for a
cystic structure. Fine-needle aspiration combined with CT will diagnose cystic lesions
with sufficient accuracy that surgical excision is infrequently needed, especially if the
mass is seen to diminish in size after aspiration. Human immunodeficiency virus (HIV)
infection must be ruled out, especially with lymphoepithelial lesions, because of the high
frequency of occurrence in HIV patients. Cysts have not been reported to degenerate into
cancer, but rarely an occult neoplasm may be associated. Asymptomatic masses may be
simply observed. Echavez et al. (17) made an excellent review of various treatments.
Simple aspiration has minimal morbidity but poor results. Radiotherapy may be effective,
but it seems a poor option for benign disease because of the associated morbidity.
Surgical resection is effective, although cysts may recur in residual tissue. They reported
treating patients with tetracycline sclerosis by direct injection of the cysts, without any
complications other than short-term pain and swelling. This method has also been used
successfully at our institution with one patient. In a symptomatic patient with high
likelihood of lymphoepithelial cyst, this is a very useful option with minimal morbidity.
Vargas et al. (18) injected botulinum toxin A subcutaneously near the mass after
diagnostic aspiration of postparotidectomy sialoceles in four patients. Sialoceles had been
present for 1.5 to 6 months, despite other treatments, and one had a chronic salivary-
cutaneous fistula. Total resolution occurred with one treatment in all four patients with 7-
to 13-month follow-up, and there was no facial nerve weakness in any case.
Both tetracycline and botulinum appear to be effective in treatment of these cysts.
Although tetracycline may be associated with local irritation, and therefore more
immediate local pain, it is well tolerated by patients. The only draw back to botulinum
toxin is the potential for facial nerve dysfunction.
XEROSTOMIA
Xerostomia is familiar to all otolaryngologists, especially after upper aerodigestive tract
(UADT) radiation, which is one of the most severe and difficult forms of xerostomia to
treat. Rather than decrease the number of cells, radiation may initially damage the cell
membrane receptor G protein, whereas later damaging a second-messenger downstream
to the G protein (19). Patients may often swallow well after UADT surgery but have great
difficulty after their succeeding radiation therapy. Although other factors, such as
radiation effect to pharyngeal muscles may be involved, xerostomia no doubt plays a
role. There is a wide range in the degree of xerostomia and associated disability after
radiation. Patients may have little problem, may take a limited solid diet or oral liquids
only, or may even be gastrostomy dependent. In addition, speech may be affected by
salivary output to some degree. Because many thousands of patients have xerostomia as a
result of UADT radiation or other diseases such as graft-versus-host disease or Sjgren
syndrome, treatment of the symptoms is a significant issue.
Because pilocarpine is a muscarinic receptor agonist, it has been used to prevent and/or
ameliorate xerostomia. Treatment after radiation may increase salivary flow, but
generally the patients are dependent on it for life, because it affords no reparative action.
Treatment with pilocarpine during radiation has been shown to have some protective
effect, although the mechanism has not been entirely clear. A recent study (20) indicated
a radioprotective effect due to stimulation of nondamaged cells. The protective effect
was present in rats up to a single radiation dose of 30 Gy, but the protection
disappeared at higher levels. The study showed that the continual salivary output is due to
hyperstimulation of the undamaged cells and that high preradiation flow rates alone do
not seem to correlate with parotid flow rates after radiation (21). Pilocarpine is therefore
not a true radioprotective agent that decreases radiation damage to the cells. The benefit
from pilocarpine lies in its ability to stimulate undamaged cells rather than protect cells
from radiation damage. On the other hand, there is histologic evidence of increased
numbers of secretory cells in irradiated glands of pilocarpine-treated animals.
Interestingly, mucus-producing glands, such as those on the hard palate, seem to have
less damage after equivalent doses of radiation and therefore respond better to pilocarpine
than the serous-producing parotid glands (22).
Amifostine has recently been used as a chemoprotectant against cisplatinum toxicity, but
it also seems to diminish mucositis and xerostomia. Amifostine is a prodrug that is
dephosphorylated to become the active free thiol metabolite in tissues. It binds and
detoxifies reactive metabolites of cisplatinum and acts as a scavenger of free radicals.
Normal tissues have a higher concentration and more effective action of the drug due to a
more favorable local interstitial milieu. This allows for normal tissue sparing without
decreasing tumor cytotoxicity. Amifostine has also been demonstrated to be effective in
decreasing incidence and severity of xerostomia due to radiation, when given during
radiation treatments (23). Amifostine has been associated with side effects such as
significant hypotension, making it less appealing for use with a several week course of
radiation. Lower doses decrease the hypotensive effect, but this leaves open the question
of efficacy with a lower dose. As a true radioprotectant, it would seem to be a better
choice during radiation than pilocarpine, which affords no actual protection from
radiation-induced cellular damage. The effects of either drug must be taken into account
and the use weighed accordingly. Becuase there is no contraindication to taking the drugs
together, concurrent use during radiation may be an additional avenue of prevention of
xerostomia.
PAROTID SURGERY
Preoperative Evaluation
Preoperative evaluation of the facial nerve in patients with parotid tumors has
traditionally been performed by observation of facial movement or tone, typically
applying the House-Brackman scale for uniformity. Facial electroneuronography (EnoG)
elicits an objective reproducible response that is not measurable by inspection alone.
Although neurotologists have long used ENoG for facial nerve evaluation, EnoG use in
parotid surgery is uncommon. Bendet et al. (24) found that a significant decrease in
preoperative EnoG response indicated nerve involvement that was not evident on clinical
examination. The lowered response also correlated with postoperative facial dysfunction.
When the preoperative EnoG was reduced by more than 80%, all patients were found to
have facial nerve involvement. EnoG did not correlate with facial nerve function for
benign tumors. This method would seem to be a more objective evaluation of facial nerve
function than physical examination. It may give preoperative insight to the surgeon and
may be helpful in preoperative counseling. The only drawback is the lack of equipment
by head and neck surgeons and whether such detail is needed. Although knowing the
EnoG will not change the course of the facial nerve function, it may be helpful in
assessing prognosis.
Nerve Dissection
Dissection of the facial nerve is universally performed with parotidectomy, but
techniques may vary widely. The facial nerve may be found by three standard methods,
each of which has its own use. The first is to find the main trunk as it exits the
stylomastoid foramen. The advantage of this method is that it affords direct access to the
pes anserinus, which is found inferior and deep to the tip of the tragal pointer. At the
nerve's exit from the skull, the styloid process is anterior to the nerve, but the nerve soon
crosses the styloid. The white color of the styloid and the nerve may be occasionally
confused if the area is not dissected open widely enough. The second method for finding
the nerve is to find a peripheral branch dissect and dissect it proximally. The marginal
mandibular branch is usually identified where it crosses the facial vein, but any branch
may be used. This method is most often used when an overlying mass prevents dissection
of the main trunk, although some surgeons prefer it routinely. The advantage of this
method is that it lessens the risk to the main trunk, because the peripheral branch is used
as a road map to the pes anserinus. The last method is to find the nerve via
mastoidectomy. This method is useful when the nerve trunk must be sacrificed
peripherally when a tumor has so enmeshed the nerve that the two former approaches to
it cannot be used.
Regardless of the approach, care must always be taken not to unnecessarily traumatize
the facial nerve. Using electrocautery during parotid dissection has the disadvantage of
electrical current transmission through the tissue, potentially causing nerve damage.
Using a bipolar instrument whenever cautery is needed decreases this risk. One
advantage of using electrocautery with this method is that immediate feedback occurs in
the form of facial movement, which may prevent more severe damage by alerting the
surgeon to the proximity of the nerve. (Of course, one could always make the argument
that the surgeon should always know the exact location of the nerve.) The Shaw scalpel
generates heat without spreading an electrical current that could damage the nerve.
Theoretically, it may have less likelihood of facial nerve damage because an electrical
current is not propagated with potential damage to the nerve. However, a recent study
(25) showed that 54% of patients dissected with the Shaw scalpel had postoperative facial
weakness, compared with 14% of those with the cold knife technique (P = .002). This
indicates that the heat may do damage with no facial nerve motion giving early enough
feedback. Possibly intraoperative monitoring may obviate the difference, but it may be
that damage is more likely with the Shaw knife due to the heat generated.
Intraoperative Facial Nerve Monitoring
Facial nerve monitoring itself is a controversial subject for parotid surgery. This
technique also has been used in neurotologic surgery, where the face cannot be monitored
directly and the nerve is often obscured by tumor and bone. Witt (26) found no statistical
difference in facial nerve function in 33 monitored patients compared with 20
unmonitored patients, and no permanent paralysis occurred. He concluded that
monitoring is optional. Dulguerov et al. (27) had similar findings with monitored patients
but had no unmonitored group for comparison. In parotid surgery, frequent false alarms
make the device less useful. When an alarm continues to cry wolf, it also becomes a
potential hazard because it cannot be believed. As with any technique, it must be used
consistently to be useful. In a case of postoperative facial nerve paralysis, there may be a
medical-legal question of whether the monitor was used and whether an ordinarily
prudent head and neck surgeon would have used one. However, to use a facial nerve
monitoring device simply for this concern would in itself be imprudent. There is no study
indicating the monitor has a significant utility in protecting the facial nerve, so the
surgeon must decide what works best in his or her hands.
Benign Mixed Tumors
Extent of Resection
When resecting benign tumors of the parotid, adequate margins are essential, but what
constitutes adequate margins is in question. Classically, we are taught that a complete
superficial parotidectomy is the minimal operation for a parotid tumor and that
lumpectomy is inadequate. This philosophy arose before the advent of CT, MRI, fine-
needle aspiration, and immunohistochemistry. Although these modalities are imperfect,
they can differentiate between benign and malignant tumors with a high degree of
accuracy, which may be very useful in planning surgery. A limited resection is the middle
ground between a complete superficial lobectomy and a lumpectomy, and it may be
appropriate in many cases of benign tumors. For example, it makes little sense to remove
normal parotid tissue near the zygoma for a Warthin tumor inferior to the lobule, simply
for the sake of blindly following a textbook dictum. On the other hand, when the
pathology is unknown or facial nerve anatomy is difficult, then a complete superficial
lobectomy may be needed. Arguments in favor of a limited resection include a potentially
smaller incision, less postoperative facial distortion, shorter operative time, and lower
incidence of Frey syndrome because less of the parotid is removed (7,8,9 and 10). If a
benign lesion is found to be splaying branches of the facial nerve but is easily excised
with the capsule abutting deep parotid tissue or even the masseter muscle, a complete
parotidectomy is generally not needed and resection of the masseter is not appropriate, as
long as adequate margins are obtained. Because resection of the deep lobe is not
necessary in such a scenario and there is no true lobular structure, it is difficult to demand
complete superficial lobectomy when the nerve and margins are otherwise clear.
Resection of deep lobe tumors with preservation of the superficial lobe has even been
reported (10). For malignant tumors, usually a total parotidectomy is performed, because
of the possibility of direct extension or even intraparotid nodal metastases.
Metastasizing Tumors
Pleomorphic adenomas have been reported to metastasize to cervical lymph nodes and
distant sitesthe so-called metastasizing benign mixed tumor. These tumors are
histologically indistinguishable from nonmetastasizing lesions but may be lethal despite
surgical resection and radiation (28). Metastasizing benign mixed tumors are very rare
and must be differentiated from implant metastases and second primary lesions. Early
descriptions (29) were controversial and often found to actually be other tumor cell types.
Foote and Frazell (30) presented the first confirmed report of a histologically benign
pleomorphic adenoma metastasizing to cervical lymph nodes and bone. It has been
suggested that cervical lymph node metastases should be excluded as true metastases
because they may be local extension or a second tumor (31). Chen and Tu (32) presented
a case in which the primary and cervical metastasis were histologically identical. The
authors argue that a true metastasis had occurred because there was no continuity
between the primary and the lymph nodes, no ectopic salivary tissue, and benign tumor in
the subcapsular sinus of the lymph node. Surgical excision of metastatic lesions is the
treatment of choice, and radiation may be needed, although it is unclear whether radiation
is useful (28).
Management of Recurrences
Although recurrent rates after the initial excision of pleomorphic adenomas are low,
treatment of recurrences is more difficult and less likely to be successful. The histologic
variant of the primary does not correlate with the subsequent aggressiveness of the lesion,
regardless of the apparent aggressive appearance. Carew et al. (33) reported a series of
recurrent pleomorphic adenomas. The initial procedures performed were local excision
(15), superficial or subtotal parotidectomy (13), total parotidectomy (2), and 4 could not
be determined. Four cases were originally performed at the study institution. The
recurrences were deep to the facial nerve (10), lateral to the facial nerve (15), or not
specified (6). Multifocal recurrence occurred in 17 (53%) patients. More than one prior
procedure had been done in 15 of 31 patients. Radiation was given for close or positive
margins or for multiple previous operations. In two patients, the trunk of the facial nerve
was excised because it was encased by tumor; both patients had abnormal facial nerve
function preoperatively. Single branches were sacrificed in two other patients. There was
a 67% (16/24) incidence of facial nerve dysfunction after resection in those patients who
had normal preoperative function and no nerve sacrifice, but only 2 of 16 patients had
persistent weakness. The only factor that correlated statistically with tumor control was
the extent of the original surgery. For those initially treated with local excision, 100% had
local control after salvage treatment. For those treated initially with conventional
parotidectomy and facial nerve dissection, salvage rate dropped to 63%. Control was
better after 7 years in those receiving postoperative radiation (100%) compared with no
radiation (71%), but this was not statistically significant (P < .28). Similarly, there was a
nonsignificant improved control rate when the tumor was lateral to the nerve compared
with those deep to the facial nerve (89% vs. 67%, P < .11). The question might be raised
whether these tumors are inherently more aggressive, and possibly a forme fruste of the
so-called metastasizing benign mixed tumor or whether these represent tumor implants or
even residual disease due to inadequate resection.
Tumor spill at the original operation could have increased recurrence rates, although
Buchman et al. (34) did not find an increased recurrence rate in such cases. On the other
hand, it seems likely that multifocal recurrences found outside of parotid tissue are
implant metastases. Some tumors are simply more aggressive and seem more able to
implant than others, despite the similar histologic appearance. In multifocal and multiply
recurrent lesions it may be appropriate to perform a selective neck dissection to
encompass the implants that may be present in the investing fascia but have yet become
clinically evident. There will always be a controversy regarding radiation with benign
tumors. In this relatively large series there was no statistically significant increase in
control rate, and Klijanienko et al. (28) reported two cases that were not controlled,
despite surgery and radiation. However, when a tumor recurs multiple times, radiation
always has the potential for cure or retardation of tumor growth. Because this has been
found to be the case with juvenile nasopharyngeal angiofibromas and glomus tumors, it
may also be true with pleomorphic adenomas. Because of the rarity of multiply recurrent
and metastasizing pleomorphic adenomas, this question may not ever be adequately
resolved. The last issue brought to light is when it is appropriate to sacrifice the facial
nerve in the face of a benign tumor. The study by Carew et al. (33) highlights the fact that
reoperation alone may result in permanent facial nerve palsy, despite facial nerve
preservation. Sacrifice of the nerve was especially warranted in the two cases with
preoperative facial nerve weakness. Friedman et al. (35) based the decision of whether to
sacrifice the nerve on clinical findings rather than histology: Facial nerve preservation is
ill-advised when a parotid tumor has to be transected to spare the nerve. This rule applies
even when the tumor is benign.
IMAGING
The imaging technique of choice in parotid diagnosis depends on the presumed
pathology. Plain films, either lateral neck or dental x-rays, demonstrate radiopaque
submandibular stones but are not useful for any other salivary gland problem.
Sialography has been used to diagnose stones, intraparenchymal masses, parotitis,
ectasia, or pseudoectasia and may help distinguish autoimmune disease (e.g., sicca
syndrome) from infection. However, this tends to be an academic exercise, because
therapy is generally based on symptomatology. Radiosialography offers no advantage
over CT and produces frequent false-negative results (36). CT sialography gives little
additional information that is not seen on a contrasted CT and carries the added morbidity
of occasional sialadenitis (37). The best use of CT or standard sialography is probably for
the preoperative demonstration of lacerations of the Stensen duct. MR sialography has
been shown to be useful because it requires no contrast. Salivary flow is stimulated with
ascorbic acid, allowing MRI to demonstrate the increased fluid, and this method may be
useful in recurrent parotitis (38). Sialography using intraductal gadolinium with MRI may
show some masses better than other sialographic methods. It has also been used to
demonstrate Stensen duct as a marker delineating deep and superficial lobes, but it is only
69% effective in this regard (38). Ariyoshi and Shimahara (39) used two other landmarks
to distinguish deep from superficial lobes. The first used a line connecting the lateral
surface of the posterior belly of the digastric with the lateral cortex of the ascending
mandibular ramus, the so-called facial nerve line. This method was confirmed to be
correct in seven of eight cases. Using the retromandibular vein as a dividing line was
successful in five of eight cases. Although this may have some academic interest and may
help in preoperative counseling, the surgeon should always be ready to resect the deep
lobe. It is far more important to know the proximity of the tumor to structures in the
parapharyngeal space, mandible, and skull than whether it is in the deep lobe.
A hot technetium scan is useful in diagnosing Warthin tumor in a patient who is poor
risk for surgery. Although irregular margins and cold lesions are typical of malignant
neoplasm, they may also represent inflammation. With the exception of a clinically
benign hot lesion in a patient who is a poor surgical risk, radiosialography is of little help
in guiding therapy. Sonography may image parotid abscesses and stones, but like
sialography, it has been replaced by CT. The entire parotid, parapharyngeal space,
mandible, base of skull base, and mastoid are well visualized with CT. It is especially
useful in differentiating intrinsic from extrinsic salivary gland masses. Although
sialography may show the ducts better, a contrasted CT displays ductal architecture
adequately and gives so much additional information that no other procedure should be
needed for most problems involving the salivary gland. Alternatively, MRI is superior in
distinguishing soft tissue masses and is very useful in postoperative surveillance,
especially when preoperative tumor MRI characteristics are known. In cooperative
patients MRI is useful, but motion artifacts due to swallowing, breathing, and mandibular
motion may be significant. Additionally, MRI gives little useful information about the
bony involvement of the mandible, mastoid, and skull base. Because the strengths and
weaknesses of the two modalities are somewhat complementary, complex cases may
require both MRI and CT to sort out the clinical picture.

HIGHLIGHTS
The diagnosis and the extent of resection of salivary gland
masses must be based on permanent tissue pathology from a
surgical specimen.
Although there is a role for fine-needle aspiration, frozen
section, and radiography in selected cases, sacrifice of major
structures should be based on final permanent sections or tumor
behavior.
Postoperative radiation therapy improves local control of
malignant salivary gland tumors when all gross disease and
involved structures are resected.
Although benign tumors are best treated with conservative
surgery, an aggressive recurrent tumor may rarely necessitate
radiation therapy or sacrifice of the facial nerve.
CT is the single best study for salivary gland masses.
Prophylactic neck dissection is indicated in patients with
biologically aggressive or advanced tumors of all cell types.
The stage N0 neck also should be treated in early-stage high-
grade mucoepidermoid carcinoma, squamous cell carcinoma,
high-grade adenocarcinomas, and malignant mixed tumors.
Adenoid cystic carcinoma, intermediate-grade mucoepidermoid
carcinoma, and acinic cell carcinomas may have varying
degrees of innate biologic aggressiveness, depending on
histologic description and as yet uncharacterized differences in
grade.
For patients with cystic lesions of the parotid, HIV infection
and neoplasm must be ruled out. Tetracycline sclerosis offers
the best and least morbid treatment for symp-tomatic
lymphoepithelial cysts.
Extracorporeal electromagnetic lithotripsy for salivary stones is
a new treatment that is effective and without major
complication.
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28. Klijanienko J, El-Naggar AK, Servois V, et al. Clinically aggressive metastasizing pleomorphic
adenoma: report of two cases. Head Neck 1997;19:629633.
29. Mulligan RM. Metastasis of mixed tumors of the salivary glands. Arch Pathol 1943;35:357365.
30. Foote FW, Frazell EL. Tumors of the major salivary glands. Cancer 1953;6:10651133.
31. Qureshi AA, Gitelis S, Templeton AA, et al. Benign metastasizing pleomorphic adenoma. A
case report and review of literature. Clin Orthop Relat Res 1994;308:192198.
32. Chen IH, Tu HY. Pleomorphic adenoma of the parotid gland metastasizing to the cervical lymph
node. Otolaryngol Head Neck Surg 2000;122:455457.
33. Carew JF, Spiro RH, Singh B, et al. Treatment of recurrent pleomorphic adenomas of the parotid
gland. Otolaryngol Head Neck Surg 1999;121:539542.
34. Buchman C, Stringer SP, Mendenhall WM, et al. Pleomorphic adenoma: effect of tumor spill and
inadequate resection on tumor recurrence. Laryngoscope 1994;104:12311234.
35. Friedman M, Rice DH, Spiro RH. Difficult decisions in parotid surgery. Otolaryngol Clin North
Am 1986;19:637.
36. Gates GA. Radiosialographic aspects of salivary gland disorders. Laryngoscope 1972;82:115.
37. Mancuso A, Rice D, Hanafee W. Computed tomography of the parotid gland during contrast
sialography. Radiology 1979;132:211.
38. Eracleous E, Kallis S, Tziakouri C, et al. Sonography, CT scan and CT scan sialography, MRI and
MRI sialography in investigation of the facial nerve and the differentiation between deep and
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

41 UPPER DIGESTIVE TRACT ANATOMY AND PHYSIOLOGY
Head & Neck SurgeryOtolaryngology
41




UPPER DIGESTIVE TRACT ANATOMY AND
PHYSIOLOGY
JERI A. LOGEMANN

J.A. Logemann: Departments of Communication Sciences and Disorders, Northwestern University and
Departments of Neurology and OtolaryngologyHead and Neck Surgery, Northwestern University
Medical School, Evanston, Illinois.

Valve Function for Deglutition
Pressure Generation
Coordination of Oropharyngeal Swallow Events
Effects of Bolus Characteristics on the Oropharyngeal Swallow
Effects of Voluntary Control
Effects of Posture
Effects of Development and Aging
Types of Swallows
Respiratory-Swallow Coordination
Chapter References
The upper digestive tract, made up of the oral cavity, pharynx, and larynx, supports the
physiology of deglutition in addition to respiration, phonation, and articulation. To
accomplish each of these functions and the rapid transitions between them, the upper
aerodigestive tract contains a series of valves that are adjusted differently for each
function. During deglutition, the valves in the oral cavity and pharynx are adjusted to
direct the flow of food safely and efficiently from the mouth through the pharynx and
into the esophagus. At the same time, pressure is exerted on the food or liquid to move it
rapidly and cleanly, leaving minimal residue in the mouth or pharynx when the swallow
is completed. Thus, valve operation and pressure generation are the critical components
of normal, efficient, and safe operation of the upper aerodigestive tract during deglutition.
VALVE FUNCTION FOR DEGLUTITION
There are six valves that operate during swallow within the upper digestive tract: lips,
tongue, velum to back of tongue (the glossopalatal valve), velopharynx, larynx, and upper
esophageal (cricopharyngeal) sphincter (Fig. 41.1).

FIGURE 41.1. Lateral schematic view of the oral cavity
and pharynx with the six valves identified: 1, lips; 2,
tongue; 3, soft palate to tongue; 4, velopharynx; 5, larynx,
including the true vocal folds (c), the false vocal folds
and the arytenoid to epiglottic base (b), and the epiglottis
(a); and 6, the cricopharyngeal (upper esophageal)
sphincter.



The lips (orbicularis oris muscle) form the first and most anterior valve, closing around a
spoon, fork, cup, or straw to capture food and liquid in the oral cavity, preventing
drooling. Lip closure is maintained throughout the oropharyngeal stages of swallow. Lip
closure permits the generation of pressure in the oral cavity to propel the bolus
posteriorly during the oral stage of swallow. Reduction in lip closure results in loss of
food or saliva from the mouth anteriorly.
The tongue is the second and most mobile valve within the upper digestive tract and is
involved in very different ways in oral preparation and the oral and pharyngeal phases of
deglutition. The tongue is composed almost entirely of muscle fibers going in all
directions. The oral portion of the tongue is under volitional cortical control and is largely
responsible for movement of the food during chewing and oral preparation. During
mastication, the tongue positions food on the teeth, picks it up as it is crushed by the
teeth, mixes the food with saliva, and replaces it onto the teeth in a rotary lateral action.
Facial tone prevents food from falling into the lateral sulci during chewing. At the end of
oral preparation, the tongue rapidly brings the food particles together into a cohesive ball
or bolus, in preparation for initiation of the oral stage of swallow. If a large amount of
food is placed in the mouth, the tongue subdivides the material, forming a bolus that is
the right volume in relation to the food's viscosity. The thicker the food viscosity, the
smaller the bolus. Excess food is put to the side by the tongue for later swallowing.
The tongue then begins the oral stage by making lateral contact with the anterior and
lateral alveolar ridge. Vertical midline tongue-to-palate contact progresses posteriorly,
propelling the bolus ahead of it toward the pharynx (1). The pressure of the tongue
against the palate increases as bolus viscosity increases. All this lingual control during
oral preparation and the oral stage of swallow is thought to be under voluntary cortical
control. When there is no peripheral seal of the sides of the tongue to the alveolar ridge or
reduced range of tongue motion or damage to fine motor control of the tongue, the person
may experience difficulty chewing, controlling food in the mouth, forming a bolus, or
propelling the bolus posteriorly.
As the bolus passes the back of the tongue, the pharyngeal swallow should trigger. This is
accomplished by peripheral afferent input to the cortex and the brainstem swallowing
centers (the nucleus solitarius and the nucleus ambiguus) and a motor program output.
When the pharyngeal swallow triggers, a number of physiologic events occur in the
pharynx. When the bolus tail reaches the valleculae during the pharyngeal swallow, the
base or pharyngeal portion of the tongue moves rapidly backward to contact the inward
moving posterior and lateral pharyngeal walls. This base of tongue action applies
pressure to the tail of the bolus, propelling it cleanly through the pharynx. Neurologically,
this base of tongue retraction during the pharyngeal swallow is under brainstem
(medullary) control. If there is reduced base of tongue retraction, such that the tongue
base does not contact the pharyngeal walls, there will be residue in the valleculae after
the swallow.
The soft palate contact to the back of the tongue makes up the third or glossopalatal
valve, which is operative while holding a bolus before beginning the oral stage of
swallow (1). As food is held in the mouth or gently manipulated before swallow, the soft
palate is actively pulled down and forward by the palatoglossus muscle to contact the
back of the tongue, which is elevated slightly. Closure of this posterior oropharyngeal
valve prevents premature loss of food or liquid into the pharynx and widens the nasal
airway to ensure easy nasal breathing during chewing and oral manipulation of food.
During active chewing, this valve does not operate so that premature spillage of food into
the pharynx while chewing is quite normal in individuals of all ages. While sucking
liquid into the mouth from a straw, the soft palate is also normally pulled down in contact
with the back of the tongue so that suction is created intraorally. After the liquid bolus is
drawn into the mouth through the straw, the oral swallow is initiated, and the soft palate
elevates sway from the back of the tongue. It is also possible to suck liquid from a straw
using an inhalation with an open airway and an elevated and retracted palate. Sucking in
this manner can increase the risk of inhaling food into the airway.
The fourth valve, the velopharyngeal port, closes during the pharyngeal phase of swallow
to prevent the entry of food or liquid into the nasal cavity. Velopharyngeal closure may
be accomplished using velar elevation (levator muscle) and retraction (palatopharyngeal
muscle) alone or in combination with anterior movement of the posterior pharyngeal wall
(superior pharyngeal constrictorPassavant pad) or mesial movement of the lateral
pharyngeal walls (superior constrictor). The adenoid pad may also contribute to
velopharyngeal closure. If complete velopharyngeal closure is not attained during
swallow, nasal regurgitation may occur.
The fifth valve, the larynx, closes at three different levels during swallow to prevent the
entry of food into the airway. The true vocal folds close first, followed by the false vocal
folds with anterior tilting of the arytenoid cartilage to contact the base of the epiglottis
and close the laryngeal entrance. Finally, the epiglottis is folded over the top of the
airway biomechanically. The larynx, including the cricoid cartilage, is suspended in the
neck by muscles (thyrohyoid) and ligaments attached to the hyoid bone. The hyoid, in
turn, is suspended in the neck by the suprahyoid muscles (anterior digastric, mylohyoid,
and geniohyoid anteriorly and the stylohyoid and posterior digastric posteriorly).
Contraction of these muscles can move the hyoid in various directions depending on the
function underway.
During the pharyngeal swallow, the hyoid and larynx elevate and move forward. As the
larynx and hyoid elevate, the epiglottis is folded to a horizontal position. Tongue base
retraction brings the tip of the epiglottis backward and in contact with the posterior
pharyngeal wall and continues to squeeze the epiglottis down against the posterior
pharyngeal wall, bringing the epiglottis to its most inferior position. As the bolus
envelops the epiglottis, the downward pressure of the bolus contributes to this epiglottal
descent. As the bolus passes through the pharynx and the tongue base moves anteriorly
toward its rest position, the epiglottis elevates and moves anteriorly with the tongue base.
When the tip of the epiglottis is no longer in contact with the posterior pharyngeal wall,
the elasticity in the cartilage causes it to spring back to its vertical position within 0.03 to
0.06 seconds.
If the airway fails to lift well during the swallow, part of the bolus is usually captured at
the entrance to the airway as it passes through the pharynx. This residual food at the top
of the airway may be aspirated after the swallow. If the laryngeal entrance (arytenoid
tilting anteriorly to contact the epiglottic base and contracted false vocal folds) fails to
close, food can penetrate into the airway entrance and may be aspirated after the swallow.
If the entire larynx fails to close, food or liquid passes through the larynx into the trachea
during the pharyngeal swallow.
The cricopharyngeal valve or upper esophageal sphincter (UES) is the sixth valve and
serves to prevent the entry of air into the esophagus during respiration. During swallow,
the UES opens to allow bolus passage into the esophagus. The anatomy and physiology
of this valve are complex. Figure 41.2 presents the anatomy of this sphincter. The
cricopharyngeal muscle is attached to the lateral aspects of the cricoid cartilage.
Therefore, the cricopharyngeal muscle is comprised of the posterior and lateral walls of
the UES. The anterior wall of the sphincter is the cricoid lamina. The cricopharyngeal
sphincter, then, is a musculoskeletal sphincter, that is, the cricopharyngeal muscle and the
cricoid cartilage.

FIGURE 41.2. Lateral view diagram of the hyolaryngeal
suspension system and its relationship to the
cricopharyngeal sphincter.



The cricopharyngeal muscle varies in its degree of contraction at rest. When stressed
(such as when a nasogastric or manometric tube passes through the UES), the degree of
muscle contraction is greater. At other times, the level of contraction may be minimal. In
sleep, the cricopharyngeal muscle is completely relaxed. During the pharyngeal swallow,
as the bolus head (leading edge) leaves the valleculae, the UES opens.
Opening of the UES is a complex event. First, the cricopharyngeal muscle relaxes.
However, this muscle relaxation does not open the sphincter. Rather, muscle relaxation is
considered to be an enabling event, allowing the larynx to move up and forward. One
tenth of a second after the cricopharyngeal muscle relaxes, opening of the UES is
observed radiographically (2,3). Opening occurs as the larynx and hyoid move anteriorly
and the cricoid lamina is jerked anteriorly away from the posterior pharyngeal wall. Thus,
the UES is opened by anterior movement of the hyolaryngeal complex. As the bolus
passes through the sphincter, the pressure of the bolus increases the width of UES
opening (2,3). If the cricopharyngeal sphincter (UES) fails to open long or wide enough,
there will be residue remaining in the piriform sinus after the swallow. Most often, failure
of the UES to open long or wide enough is caused by disorders of hyolaryngeal elevation
and anterior movement or bolus pressure.
PRESSURE GENERATION
The second major component of deglutition is the generation of pressure on the bolus to
drive it from the mouth, through the pharynx, and into the esophagus. Figure 41.3 and
Figure 41.4 present the major sources of pressure generation during the oral and
pharyngeal phases of swallow. The oral portion of the tongue propels the bolus
posteriorly during the oral phase of swallow, lifting the bolus and exerting pressure
against the palate as it rolls the bolus toward the oropharynx.

FIGURE 41.3. Lateral schematic view of the pressure
generators in the oral cavity and pharynx, including the
oral tongue, the base of the tongue, and the pharyngeal
constrictors.



FIGURE 41.4. Anterior view of the pharyngeal elevators
and the directions of pharyngeal contraction during
swallow.



As the bolus passes from the mouth and the pharyngeal swallow is triggered, the
pharyngeal pressure generators are activated. The pharynx lifts with the larynx as it
elevates. The larynx elevates approximately 2 cm and the pharynx is shortened by
approximately 2 cm, or one third of its total length during the pharyngeal swallow in
younger adults (under age 65). In older adults, this movement may be reduced by 0.5 cm.
The pharyngeal constrictors contract, moving the posterior pharyngeal wall anteriorly and
the lateral pharyngeal walls medially and narrowing the pharyngeal diameter sequentially
from top to bottom. As the pharynx becomes physically smaller in length and width, the
bolus tail has reached the valleculae at the base of the tongue. The tongue base then
retracts over the bolus to contact the posterior pharyngeal wall as it contracts and bulges
anteriorly. Tongue base retraction acts like a piston during the swallow, moving the bolus
through a chamber (the pharynx) of decreasing size and into the esophagus. If the tongue
base fails to retract sufficiently to make complete contact to the inward moving
pharyngeal walls, residual food or liquid will remain in the valleculae after the swallow.
If there is a unilateral pharyngeal weakness, food will remain in the piriform sinus on the
damaged side of the pharynx after the swallow. If both sides of the pharynx fail to
contract, food will be left on both sides of the pharynx in the piriform sinuses.
COORDINATION OF OROPHARYNGEAL SWALLOW EVENTS
A normal oropharyngeal swallow requires that all valves and pressure generators operate
normally and that these physiologic elements occur in the correct sequence. Oral
preparation precedes the oral stage of swallow. Oral preparation involves lip closure and
lingual manipulation of the bolus to break it down to a consistency ready for swallow.
During mastication, the mandible moves in a lateral rotary motion in coordination with
lateral rolling tongue movements that bring the bolus onto the biting surfaces of the teeth.
During the act of chewing, the velopharynx is open to facilitate nasal breathing, the
larynx is open, and the cricopharyngeal region is closed. At the termination of oral
preparation, the food or liquid is brought together into a cohesive bolus by rapid and
finely coordinated tongue movements. All the pleasure of eating occurs during oral
preparation.
Before the onset of the oral stage of deglutition, the bolus is held on the floor of the
mouth or between the tongue and the palate. If the bolus is held on the floor of the mouth,
the front tongue lifts the bolus into the superior position at the onset of the oral swallow.
At the initiation of the oral phase, the tongue elevates the bolus against the palate, rolling
and squeezing it posteriorly toward the oropharynx. As the bolus passes the faucial arches
and the back of the tongue and enters the pharynx, the pharyngeal stage of swallow is
triggered. The exact sensory stimulus needed to elicit the onset of pharyngeal swallow
events has not been clearly identified. Both the bolus and tongue movement appear to be
important components of the sensory stimulus. The region stimulated by the bolus and
tongue movement is innervated by the glossopharyngeal cranial nerve (IX), which sends
afferent input to the medullary swallow center. As the leading edge of the bolus reaches
the pit of the valleculae and the oropharynx, sensory input is carried to the swallow center
by the vagus nerve (cranial nerve X). In normal swallowing, the pharyngeal swallow is
triggered as the head of the bolus passes the back of the tongue. If the bolus head (leading
edge) passes into the valleculae and the pharyngeal swallow has not been elicited, the
pharyngeal swallow is described as delayed. As long as the pharyngeal swallow is
delayed, the airway is open. The patient is at risk for aspirating the bolus before the
pharyngeal swallow is triggered, especially with liquids, which move quickly by gravity.
When the pharyngeal swallow triggers, the hyoid and larynx begin to elevate and move
anteriorly, the pharynx shortens, and the velopharyngeal valve closes. The airway closes
as the larynx achieves approximately 50% of its elevation. The bolus is propelled by oral
tongue movement into the pharynx. When the tail of the bolus reaches the valleculae, the
tongue base retracts and the pharyngeal walls contract, applying pressure to the bolus in
the pharynx. The cricopharyngeal valve opens as the bolus is moving under pressure from
the valleculae to the piriform sinuses. Airway closure and cricopharyngeal opening
always occur within 0.03 seconds of each other unless the airway is closed voluntarily at
an earlier time. Thus, the airway is closed and protected as the esophagus is opened to
receive the bolus that is being driven through the pharynx under pressure. This entire
sequence of pharyngeal events takes place in less than 1 second.
EFFECTS OF BOLUS CHARACTERISTICS ON THE
OROPHARYNGEAL SWALLOW
Until recently, the oropharyngeal swallow was considered a relatively unvarying event.
Recent investigations of swallow physiology with calibrated boluses of various volumes
and viscosities have revealed systematic changes in duration of pharyngeal swallow
events and their temporal relationships as these bolus variables are changed (4). Airway
closure duration and cricopharyngeal opening duration increase systematically as bolus
volume increases and as bolus viscosity increases. However, these two events generally
occur within 0.03 seconds of each other, regardless of bolus volume. Lingual palatal
pressures, electromyographic activity, and intrabolus pressures in the pharynx increase as
bolus viscosity increases. Oral and pharyngeal transit times of the bolus increase as bolus
volume increases and viscosity increases. The temporal relationship of the oral and
pharyngeal stages of swallow also changes systematically with bolus volume. On
swallows of small volumes (1 to 5 mL), the oral stage proceeds first, followed by the
pharyngeal stage. On swallows of larger volumes (10 to 20 mL), the oral and pharyngeal
stages occur essentially simultaneously. The neural control underlying these systematic
changes in the oropharyngeal swallow has not been clearly defined. It has been
hypothesized that afferent input from the oral cavity, particularly from the tongue as it
manipulates the food or liquid and shapes around it to initiate the oral stage of swallow,
to the cortex and medullary swallow center modulates these physiologic changes, because
many of these systematic changes in the swallow begin while the bolus is still in the oral
cavity. Understanding these systematic changes in normal pharyngeal swallow
physiology with various bolus types helps to explain the difficulties of dysphagic patients
with various types of boluses.
EFFECTS OF VOLUNTARY CONTROL
Voluntary control can be exerted over many components of the pharyngeal swallow (5).
The airway can be closed voluntarily at the vocal folds (supraglottic swallow) or at the
entrance to the airway (super-supraglottic swallow) (5). The duration of laryngeal
elevation can be prolonged voluntarily, thereby prolonging the duration of
cricopharyngeal opening (Mendelsohn maneuver). The muscle effort used during the oral
and pharyngeal phases of swallow can be modified (the effortful swallow). These
voluntary modifications are used as therapy strategies for specific pharyngeal swallowing
disorders and are sometimes used spontaneously in the course of normal swallows. For
example, before taking a large swallow of liquid from a glass or cup, many normal
individuals inhale and hold their breath, thus closing their airway before swallowing as an
added protection. This action is essentially the supraglottic swallow.
EFFECTS OF POSTURE
Changing head position changes pharyngeal dimensions and the direction of food flow.
With the chin tucked, the entire anterior wall of the pharynx (the tongue base and
epiglottis) is pushed posteriorly and the airway entrance is narrowed. With the head
rotated, one side of the pharynx (the side rotated toward) is closed off from the passage of
the bolus. Tilting the head to one side directs food down that side of the oral cavity and
pharynx. Lifting the chin decreases oral transit time by using gravity to empty food from
the mouth. Lying the patient down changes the direction of gravity on any residual food
left after the swallow. When the patient is lying down, any residual food simply adheres
to the pharyngeal walls rather than falling down the airway after the swallow when the
patient returns to breathing. Postural changes are often used as compensatory strategies in
the management of swallowing disorders (6).
EFFECTS OF DEVELOPMENT AND AGING
During infancy, suckle feeding is used. Suck swallow involves multiple tongue pumping
of small amounts of liquid from the nipple, which are collected in the posterior oral
cavity or valleculae. When an adequate amount has collected, the pharyngeal swallow
triggers. Then the pharyngeal swallow proceeds as in adults. Most normal infants utilize a
particular pattern or number of tongue pumps with some variation. Usually one to four
tongue pumps are used to generate a bolus. More than eight pumps before a swallow is
considered abnormal. When infants take discrete amounts of liquid, the oral swallow is
similar to that of adults, with a single well-coordinated tongue action propelling the bolus
backward.
In adults over age 60, there is a slight increase (approximately 0.4 seconds) in the time
required to trigger the pharyngeal phase of swallow. There is also a slight prolongation of
oral transit time of the bolus and duration of cricopharyngeal opening. Adults over age 60
also tend to hold the bolus on the floor of the mouth before the swallow, requiring them
to pick up the bolus and bring it onto the surface of the tongue as they initiate the
swallow. This added action may be the cause of the prolonged oral transit time. There is
no documented increase in frequency of aspiration or in the amount of residue in the
mouth or pharynx with aging. There is, however, an increase in frequency of penetration
in older individuals, that is, the entry of food or liquid into the airway entrance during the
swallow with the complete clearance of material from the airway before the swallow is
complete. In normal men over the age of 80, there is early evidence that the extent of
hyoid and laryngeal movement is reduced. This may relate to the frequency of
penetration, because reduced elevation may allow the penetration to occur.
Unfortunately, there are no studies of development of oropharyngeal swallow physiology
from infancy to adulthood and few studies of swallowing in normal healthy adults over
the age of 80.
Further insight into the association between aging and progressively increasing
swallowing difficulty is provided in a report that documents reduced anteroposterior
opening of the UES and a decrease in the anterior excursion of the hyoid bone and the
thyroid cartilage in normal elderly subjects (7). These changes are associated with an
increased bolus pressure and suggest higher outflow resistance in the elderly than in the
young.
TYPES OF SWALLOWS
There are many different swallow types, that is, systematic variations in the
oropharyngeal physiology used to move food from the mouth to the esophagus in
addition to the variations described previously. This range of swallow types results from
changes in bolus volume, viscosity, voluntary control, and age. During saliva swallowing,
the pharyngeal phase may be elicited without any oral activity. If liquid is chugged
down in large amounts, the airway is voluntarily closed, the cricopharyngeal valve is
voluntarily opened, and the liquid is literally dropped from the mouth into the pharynx
and esophagus in a steady flow. It is likely that there are other normal swallow variations
that have not been documented. Understanding the normal systematic variations in
swallow physiology is important in understanding patient complaints of swallow
problems.
A recent report describes the use of functional magnetic resonance imaging to map the
patterns of cortical activation associated with different types of dry and bolus swallows.
The investigators found that activation of the primary motor and somatosensory cortices
and other sensory-motor areas could be documented. They concluded that the differential
distribution of cortical activity with different swallowing tasks suggests differential
functional organization within the brain. A better understanding of these normal
mechanisms may facilitate improvements in our therapeutic interventions for neurogenic
and postsurgical dysphagia (8).
RESPIRATORY-SWALLOW COORDINATION
In the last several years, there has been increased interest in the temporal and
biomechanical shifts accomplished by the upper aerodigestive tract between respiration
and swallowing. Studies of normal individuals have reported that most frequent normal
coordination involves interrupting the exhalatory phase of respiration with the swallow
and briefly returning to exhalation after the swallow (9). The return to exhalation after the
swallow is thought to increase safety, because the exhalatory airflow may assist in
clearing any residual food or liquid from around the airway entrance. In contrast,
interrupting the inhalatory phase of respiration with a swallow is thought to be less safe
because the risk of inhaling residual food may be increased. Some preliminary data
indicate that older normal individuals (over age 60) and dysphagic patients swallow more
often by interrupting the inhalatory phase of the respiratory cycle.
The complex coordinations of the upper digestive tract during normal swallow needs to
have further study to identify all systematic and voluntary modifications that occur.
Increasing the understanding of normal swallow physiology and its coordination with
respiration and vocalization throughout the age range will improve the understanding of
dysphagic patient complaints and behaviors and increase the efficiency of treatment of
patients with swallow abnormalities. Further definition of the physiologic transitions
between swallow, respiration, and speech production should expand the knowledge of
normal neural control of the upper aerodigestive tract and should also assist in the
diagnosis of patients with early neurogenic disease.

HIGHLIGHTS
The oropharyngeal swallow comprises a series of valves that
are adjusted to direct the flow of food safely and efficiently
from the oral cavity through the pharynx and into the esophagus
at the same time that pressure is actively exerted against the
bolus by the oral tongue, tongue base, and pharyngeal walls.
Airway closure at the vocal folds and at the airway entrance,
that is, the false vocal folds and arytenoid tilting to epiglottic
base, is neurologically controlled.
Movement of the epiglottis is the biomechanical result of
hyolaryngeal vertical and anterior movement, bolus pressure,
and tongue base retraction.
Opening of the UES is controlled biomechanically and involves
a complex series of muscular actions, beginning with relaxation
of the cricopharyngeal muscle, followed by anterior movement
of the hyolaryngeal complex and pressure of the bolus.
Airway closure and cricopharyngeal opening are time locked so
that they always occur within 0.03 seconds of each other as the
bolus is driven into the pharynx under pressure. This
relationship remains the same at all bolus volumes.
Pressure on the bolus tail is generated by the oral tongue, the
tongue base, and the pharyngeal walls.
Many aspects of oropharyngeal swallow physiology change
systematically with increases in bolus volume, bolus viscosity,
and the voluntary control exerted over selected physiologic
components of the swallow.
Normal swallow physiology also differs in infants, young
adults, older adults (over age 60), and the oldest old (80+ years
of age).
Head posture affects the dimensions of the pharynx and the
direction of food flow.
As future research elucidates other systematic changes in
normal swallow physiology, the understanding of dysphagic
patient complaints and disorders will im-prove, as will the
efficacy of treatment strategies. The oropharyngeal swallow
comprises a series of valves that are adjusted to direct the flow
of food safely and efficiently from the oral cavity through the
pharynx and into the esophagus at the same time that pressure is
actively exerted against the bolus by the oral tongue, tongue
base, and pharyngeal walls.
Airway closure at the vocal folds and at the airway entrance,
that is, the false vocal folds and arytenoid tilting to epiglottic
base, is neurologically controlled.
Movement of the epiglottis is the biomechanical result of
hyolaryngeal vertical and anterior movement, bolus pressure,
and tongue base retraction.
Opening of the UES is controlled biomechanically and involves
a complex series of muscular actions, beginning with relaxation
of the cricopharyngeal muscle, followed by anterior movement
of the hyolaryngeal complex and pressure of the bolus.
Airway closure and cricopharyngeal opening are time locked so
that they always occur within 0.03 seconds of each other as the
bolus is driven into the pharynx under pressure. This
relationship remains the same at all bolus volumes.
Pressure on the bolus tail is generated by the oral tongue, the
tongue base, and the pharyngeal walls.
Many aspects of oropharyngeal swallow physiology change
systematically with increases in bolus volume, bolus viscosity,
and the voluntary control exerted over selected physiologic
components of the swallow.
Normal swallow physiology also differs in infants, young
adults, older adults (over age 60), and the oldest old (80+ years
of age).
Head posture affects the dimensions of the pharynx and the
direction of food flow.
As future research elucidates other systematic changes in
normal swallow physiology, the understanding of dysphagic
patient complaints and disorders will im-prove, as will the
efficacy of treatment strategies.
CHAPTER REFERENCES
1. Kahrilas PJ, Lin S, Logemann JA, et al. Deglutitive tongue action: volume accommodation and
bolus propulsion. Gastroenterology 1993;104:152.
2. Dantas RO, Dodds WJ, Massey BT, et al. Manometric characteristics of the glossopalatal
sphincter. Dig Dis Sci 1990;35:161.
3. Kahrilas PJ, Lin S, Chen J, et al. Oropharyngeal accommodation to swallow volume.
Gastroenterology 1996;111:297.
4. Bisch EM, Logemann JA, Rademaker AW, et al. Pharyngeal effects of bolus volume, viscosity
and temperature in patients with dysphagia resulting from neurologic impairment and in normal
subjects. JSHR 1994;37:1041.
5. Ohmae Y, Logemann JA, Kaiser P, et al. Effects of two-breath holding maneuvers on
oropharyngeal swallow. Ann Otol Rhinol Laryngol 1996;105:123.
6. Logemann JA, Rademaker AW, Pauloski BR, et al. Effects of postural change on aspiration in
head and neck surgical patients. Otolaryngol Head Neck Surg 1994;110:222.
7. Kern M, Bardan E, Arndorfer R, et al. Comparison of upper esophageal sphincter opening in
healthy asymptomatic young and elderly volunteers. Ann Otol Rhinol Laryngol 1999;108:982.
8. Mosier K, Patel R, Liu WC, et al. Cortical representation of swallowing in normal adults:
functional implications. Laryngoscope 1999;109:1417.
9. Martin BJW, Logemann JA, Shaker R, et al. Coordination between respiration and swallowing:
Respiratory phase relationships and temporal integration. J Appl Physiol 1994;76:714.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

42 UPPER AIRWAY ANATOMY AND FUNCTION
Head & Neck SurgeryOtolaryngology
42




UPPER AIRWAY ANATOMY AND FUNCTION
GAYLE E. WOODSON

G.E. Woodson: Department of OtolaryngologyHead and Neck Surgery, University of Florida,
Gainesville, Florida.


Pharyngeal Anatomy
Laryngeal Anatomy
Skeleton
Muscles
Nerve Supply
Mucosal Cover
Respiratory Physiology
Cough
Valsalva Maneuver
Regulation of Airflow
Sensory Input to Respiratory Control
Circulatory Reflexes
Speech
Phonation
Resonance
Articulation
Sensory Input to Speech Control
Chapter References
The upper airway includes the nasal and oral cavities, the pharynx, and the larynx. The
functional design is far from ideal because ingested food and water must traverse the
upper airway to reach the alimentary tract. The pharynx must serve two conflicting
functions. It must rapidly constrict during swallowing, yet maintain patency during the
negative pressure generated by inspiration. Breathing and speech must be interrupted
during a swallow. The precarious arrangement of the airway is a product of its evolution
and embryology. The trachea and lungs evolved as an offshoot of the digestive tract, and
this origin is reflected in the development of human embryos. The lung buds arise from
the lower pharynx.
In all nonhuman mammals, the common upper chamber for eating and breathing poses
little problem, because there are functionally separate channels for breathing and eating,
formed by the interdigitation of the epiglottis and the soft palate. The central channel,
leading from the nose to the larynx, is for breathing, with a pathway for swallowing on
either side, leading from the mouth to the esophagus. This configuration persists in
human infants and explains obligate nasal breathing in neonates. In the second year of
life, however, descent of the larynx results in elongation of the pharynx and separation of
the soft palate and larynx. This results in greater vocal power and diversity in articulation,
but it also makes the process of swallowing considerably more complex. The purpose of
this chapter is to provide a basis for understanding the processes of breathing and speech.
Because nasal and oral anatomy are covered in other parts of this text, the following
section focuses primarily on the larynx and pharynx.
PHARYNGEAL ANATOMY
The pharynx is an irregularly tubular structure, extending from the base of the skull to the
esophageal inlet (Fig. 42.1). The posterior and lateral walls of the pharynx are composed
of three pharyngeal constrictor muscles attached to the cervical vertebrae posteriorly. The
pharynx has anterior openings into the nasal and oral cavities, and inferiorly it opens into
the larynx and esophagus. There are three segments: the nasopharynx, the oropharynx,
and the hypopharynx. The nasopharynx can be sealed off from the oropharynx by
simultaneous elevation of the soft palate and formation of a fold in the pharyngeal walls,
known as Passavant ridge. Complete physical examination of the pharynx requires a
mirror or endoscope, because only the posterior wall of the oropharynx is visible by
transoral inspection.

FIGURE 42.1. Sagittal view of upper airway.



The superior constrictor is suspended from the base of the skull, the medial pterygoid
plate, the pterygomandibular raphe, the mylohyoid line of the mandible, and the lateral
tongue. The anterior attachments of the middle constrictor are the hyoid bone and the
stylohyoid ligament. The inferior constrictor attaches to the thyroid and cricoid cartilages.
Activation of these muscles constricts the pharynx; there is no evidence to support the
concept that they contribute to stability of the airway. Pharyngeal patency during the
negative pressure generated with inspiration is maintained by muscles that dilate the
lumen by pulling the base of the tongue or hyoid bone anteriorly. These muscles include
the genioglossus, the geniohyoid, and the anterior belly of the digastric muscle.
LARYNGEAL ANATOMY
The most superior portion of the larynx is the epiglottis, which projects posteriorly into
the pharynx. The vallecula is the pouch between the base of the tongue and the epiglottis.
Interiorly, the glottis is seen as a roughly triangular opening during inspiration and a
narrow slit during phonation. The true vocal folds comprise the anterior edges of the
glottis. Superior and lateral to the true vocal folds are the false vocal folds. The ventricle
is a narrow space between the true and false folds. The posterior glottis is formed by the
two arytenoid cartilages and the intervening mucosa. The arytenoids are the posterior
attachments of both the true and false vocal folds. Opening and closing of the glottis is
affected by movement of the arytenoids. Laterally, each arytenoid connects to the
epiglottis by an aryepiglottic fold. These folds separate the airway to the glottis from the
lateral pathways to the esophagus. These pathways are the piriform fossae, mucosal-lined
spaces lateral to the aryepiglottic folds but medial to the laryngeal skeleton (Fig. 42.2,
Fig. 42.3 and Fig. 42.4).

FIGURE 42.2. Posterior view of anterior airway.



FIGURE 42.3. Endoscopic view of the larynx.



FIGURE 42.4. Vertical section through the larynx.



Skeleton
The laryngeal skeleton is made up of several cartilages and one bone strung together in
series and suspended from the skull base and mandible (Fig. 42.5). Laryngeal motion can
be caused by both intrinsic muscles, which arise and insert on laryngeal cartilages, and
extrinsic muscles, which connect the larynx to other structures. Also, because of the
interconnections of the trachea and the laryngeal cartilages, descent of the trachea during
inspiration produces widening of the glottis.

FIGURE 42.5. Laryngeal skeleton.



The hyoid, which supports the larynx and stabilizes the hypopharynx, is roughly U
shaped, with the two free ends projecting posteriorly as the greater cornua. The lesser
cornua are two small bumps on the superior anterior surface. The hyoid is connected to
the thyroid cartilage by the broad thyrohyoid membrane. A bursa in this membrane
enhances vertical mobility of the larynx. Laterally, the edges of the membrane thicken to
form the thyrohyoid ligaments.
The thyroid cartilage is composed of two halves fused anteriorly at a sharp angle (90
degrees in males and 120 degrees in females). The posterior border has superior and
inferior cornua. The superior cornu attaches to the thyrohyoid ligament, whereas the
inferior articulates with the cricoid cartilage. The thyroid cartilage begins to gradually
ossify after the age of 20. This process accounts for many age-related changes in pitch
and resonance of the voice.
The epiglottis is a fibroelastic cartilage, attached anteriorly in the midline to the inner
surface of the thyroid cartilage and supported by the hyoepiglottic ligament. The free end
of the epiglottis projects into the hypopharynx.
The cricoid cartilage is the skeletal support of the subglottis, which is the portion of the
larynx below the vocal folds. The subglottis is the only point in the airway with a
completely rigid diameter. It has a smaller cross-sectional area than the trachea, so that a
single foreign body that is small enough to pass through the subglottis does not cause
total airway obstruction. Anteriorly, the cricoid is about 1 cm high, with a smooth curved
surface. Posteriorly, it is 2 to 3 cm high, and the superior surface is flattened centrally to
provide an area of articulation for the arytenoid cartilages. Posterolaterally, on each side,
the cricoid articulates with the inferior cornu of the thyroid cartilage to form a visorlike
apparatus, allowing rotation in a sagittal plane, which opens or closes the anterior
cricothyroid space.
Each arytenoid cartilage is a somewhat pear-shaped mass. The broad base articulates with
the cricoid in a complex synovial joint, which is essentially a shallow ball and socket,
allowing multiaxial rotation but minimal translation (1). The vocal process, an anterior
and medial projection of the arytenoid, is the posterior segment off the vocal fold (Fig.
42.6). Two other small sesamoid cartilages, the corniculate and the cuneiform, are located
superior to the arytenoid and support the aryepiglottic fold.

FIGURE 42.6. Laryngeal muscles.



Two fibroelastic membranes are important components of the larynx. The conus elasticus
provides support to the vocal fold. From its lateral attachment to the cricoid, it extends
anteriorly to the midline lower edge of the thyroid cartilage and posteriorly to the vocal
process of the arytenoid. Its free edge forms the vocal ligament. The quadrangular
membrane supports the supraglottis. It connects the epiglottis with the arytenoid and the
corniculate cartilages. The superior free edge is draped in mucosa to form the
aryepiglottic fold, whereas the inferior edge is a part of the false vocal fold (Fig. 42.7).

FIGURE 42.7. Fibroelastic membranes.



Muscles
Motion of the vocal folds is affected primarily by the intrinsic laryngeal muscles. The
posterior cricoarytenoid muscle, the only abductor of the glottis, originates from the
posterior surface of the cricoid and inserts onto the muscular process of the arytenoid.
Contraction of this muscle externally rotates the arytenoid, displacing the vocal process
superiorly and laterally, resulting in abduction of the glottis (1). The lateral
cricoarytenoid muscle is an adductor with origin on the lateral aspect of the cricoid and
insertion on the muscular process of the arytenoid. This muscle pulls the muscular
process forward, rotating the vocal process medially. The thyroarytenoid muscle arises
from the anterior inner aspect of the thyroid cartilage to insert on the vocal process of the
arytenoid. It exerts anterior traction on the vocal process, increasing vocal fold tension,
thickness, and stiffness. In the absence of cricothyroid muscle contraction, it also reduces
tension in the mucosal cover. The thyroarytenoid muscle is often considered to be divided
into two separate muscles: the medial thyroarytenoid (vocalis) and the lateral
thyroarytenoid. The cricothyroid muscle pulls the cricoid and thyroid cartilages together
anteriorly to increase the length and tension of the vocal folds. The interarytenoid muscle,
the only unpaired laryngeal muscle, adducts the vocal folds (Fig. 42.6). The smallest
laryngeal muscle, a very small band of muscle fibers between the epiglottis and
arytenoid, constricts the supraglottic inlet.
Recent evidence suggests that the control of laryngeal muscles is more complex than
previously recognized. The posterior cricoarytenoid, cricothyroid, and thyroarytenoid
muscles all appear to be composed of functionally distinct compartments with separate
nerve branches (2,3 and 4). In particular, the medial portion of the thyroarytenoid muscle
has an extremely complex nerve supply.
Extrinsic laryngeal muscles include the mylohyoid, digastric, and stylohyoid muscles,
which suspend the larynx superiorly, and the cervical strap muscles: the omohyoid,
sternohyoid, sternothyroid, and thyrohyoid. Extrinsic muscles elevate or depress the
larynx or move it anteriorly or posteriorly. Extrinsic muscle activity can indirectly
adduct, abduct, or tense the vocal folds or constrict the supraglottis.
Nerve Supply
The vagus nerve supplies the larynx through two branches, the superior laryngeal nerve
and the recurrent laryngeal nerve. The superior laryngeal nerve exits the vagus below the
nodose ganglion and branches into two divisions. The internal branch is purely sensory,
carries afferent fibers from supraglottis and vocal folds, and enters the larynx laterally
through the thyrohyoid membrane. The external branch supplies motor fibers to the
cricothyroid muscle. The recurrent laryngeal nerve supplies all other intrinsic muscles of
the larynx and mediates sensation from the subglottis and trachea. The recurrent
laryngeal nerve does not travel straight from the vagus to the larynx but first descends
into the upper mediastinum. The right recurrent laryngeal nerve curves back upward
around the subclavian artery, whereas the left descends to the ligamentum arteriosum, a
fibrous band connecting the aortic arch to the pulmonary artery. The nerves then ascend
in or near the tracheoesophageal groove to enter the larynx. The development of the
branchial arterial arch and nerve system during embryogenesis is responsible for the
circuitous route of these nerves.
Mucosal Cover
The mucosal cover of most of the upper airway is respiratory epithelium, with numerous
mucous glands (Fig. 42.8). Over the free edge of the vocal fold, however, mucosa is
adapted for periodic vibration with squamous epithelium and no mucous glands. A highly
specialized lamina propria separates the epithelium from underlying muscle (5). The
lamina propria serves as a shock absorber, so that the epithelium can vibrate freely,
without restriction by the bulky underlying muscle. It contains three layers: superficial,
intermediate, and deep. Each has unique mechanical properties because of varying
densities of elastic and collagenous fibers. The deep layer, or vocal ligament, is the
stiffest, due to a high concentration of collagen fibers. Elastic fibers are most numerous in
the intermediate layer and gradually decrease toward the epithelium and muscle (6). The
superficial layer of the lamina propria is often referred to as Reinke's space, although it is
not actually a potential space. This layer has the lowest concentration of both elastic and
collagenous fibers and offers the least impedance to vibration.

FIGURE 42.8. Vocal fold mucosa.



RESPIRATORY PHYSIOLOGY
The most primitive function of the larynx is that of a sphincter, preventing the ingress of
anything other than air into the lungs. Other functions include coughing, Valsalva
maneuver, and the regulation of airflow in and out of the lungs. The larynx also serves as
a sensory organ and contains receptors that influence the control of breathing and even
affect cardiovascular function.
Cough
Cough ejects mucus and foreign matter from the lungs and helps to maintain patency of
the pulmonary alveoli. Cough may be voluntary but more often occurs in response to
stimulation of receptors in the larynx or lower respiratory tract. A greater stimulus is
required to produce a cough during sleep, and in deep sleep a stimulus must first result in
arousal to a lighter level of sleep before cough occurs.
A cough has three phases: inspiratory, compressive, and expulsive. First, the larynx opens
very widely to permit rapid and deep inspiration. If the cough is voluntary, the degree of
glottal abduction and inspiratory effort is proportional to the intended strength of the
cough. The compressive phase is produced by tight closure of the glottis and strong
activation of expiratory muscles. During the expulsive phase, the larynx suddenly opens
widely, with a sudden outflow of air in the range of 6 to 10 L/s.
Valsalva Maneuver
The true vocal folds offer more resistance to inspiratory than expiratory airflow.
However, very tight closure of both true and false vocal folds enables the larynx to resist
very strong expiratory forces. Forced expiration against a tightly closed glottis is known
as the Valsalva maneuver. It is important in defecation because the pressure is transmitted
to the abdominal cavity and also serves to stabilize the thorax during heavy lifting by the
arms.
Regulation of Airflow
The larynx is ideally located to regulate the flow of air in and out of the lungs and is
better adapted than any other portion of the respiratory tract for producing sudden
alterations in resistance to airflow. Observations of laryngeal movement demonstrate that
the glottis widens during inspiration and narrows during expiration, and this movement
with breathing varies with respiratory demand. Opening, or abduction of the larynx,
facilitates breathing by decreasing resistance to airflow. Two forces contribute to
inspiratory opening of the larynx: longitudinal tension on the laryngeal skeleton, caused
by the descent of the trachea, and contraction of the posterior cricoarytenoid muscle.
Both these forces increase during hyperpnea. Active laryngeal abduction is a primary
action of breathing, because the posterior cricoarytenoid muscle consistently begins to
contract before the diaphragm with each inspiration. The larynx opens more widely
during inspiration with increasing effort of breathing and in response to negative upper
airway pressure.
Expiratory adduction of the larynx is sometimes a passive phenomenon, but laryngeal
abductor activity can decrease the rate of breathing by prolonging expiratory duration.
With very strong respiratory demand, the posterior cricoarytenoid muscle continues
contracting during expiration, after the diaphragm has relaxed. This results in decreased
resistance and faster outflow of air, which shortens the duration of expiration and
increases the rate of breathing. During most conditions of breathing, respiratory rate is
primarily controlled by varying the rate of exhalation.
In addition to dynamic control of airflow, the static larynx exerts mechanical influences
on airflow. At any given glottic aperture, resistance to airflow in the inspiratory direction
is much greater than resistance to expiratory flow. Because of this, conditions that cause
laryngeal obstruction, such as edema, papillomas, or laryngeal paralysis, usually produce
inspiratory stridor before expiration is impaired.
Sensory Input to Respiratory Control
The larynx is not only an effector organ; it is also richly supplied with a variety of
sensory receptors that exert influences on breathing and cardiovascular function. There
are several times more sensory fibers from the larynx than from the lungs, which have
internal surface areas of several square meters. Some responses to laryngeal stimulation
are appropriate and beneficial; however, some responses such as laryngospasm and
cardiovascular collapse appear maladaptive. These reflexes can be produced
experimentally by electrical stimulation of the superior laryngeal nerve. Such extreme
responses probably represent an oversaturation of pathways that serve a useful function at
lower levels of input. Three major types of laryngeal receptors are activated by the
process of breathing and have an influence on the central control of breathing: negative
pressure receptors, airflow (cold) receptors, and drive receptors, which are probably
proprioceptors that respond to respiratory motion of the larynx (7). Laryngeal receptors
also respond to touch and chemical stimuli.
Negative upper airway pressure increases the inspiratory activation of upper airway
dilating muscles, including the genioglossus, the geniohyoid, the ala nasi, and the
posterior cricoarytenoid muscle (8). Negative pressure sensation is primarily mediated by
the superior laryngeal nerve and is believed to be an important stimulus for maintaining
upper airway patency.
Airflow receptors have been identified in the nose and the larynx and appear to modulate
central respiratory drive. Stimulation can decrease respiratory rate or even cause apnea.
Airflow receptors behave as thermistors, responding to the temperature drop induced by
air flowing through. Thus, laryngeal flow receptors do not respond to air that has been
warmed and humidified by the nose but are activated by air that comes in through the
mouth, particularly in cold and dry weather.
A number of responses can be elicited by mechanical stimulation of the larynx, including
apnea, laryngospasm, and cardiovascular collapse. Because the larynx is in a very
protected position, such responses do not usually occur naturally. Laryngospasm, the
forceful and prolonged closure of the larynx, is most often seen in the operating room in
response to endotracheal intubation. It is most likely to occur when the patient is well
oxygenated and under light anesthesia. It occurs in the conscious state under certain
pathologic conditions such as upper respiratory infection. Sometimes a decreased
threshold for laryngospasm can persist for many months after an infection, resulting in
frequent episodes of frightening total airway obstruction. Mechanical or chemical
stimulation of the larynx can produce prolonged bronchoconstriction.
The laryngeal adductor reflex is a rapid brief closure of the true vocal folds in response to
appropriate stimulation of the mucosa innervated by the superior laryngeal nerve.
Sensory deficits in the laryngopharyngeal region can result in dysphagia and aspiration.
Recent studies have shown the importance of sensory testing in this region, especially in
predicting aspiration pneumonia risk in stroke patients (9).
Apnea in response to laryngeal stimulation probably evolved because it prevents the
aspiration of the stimulating material into the lower airway. Apnea may occur in response
to such diverse chemical agents as ammonia, phenyl diguanide, and cigarette smoke.
Water in the larynx can also inhibit inspiration under certain conditions, such as general
anesthesia, and during upper re-spiratory infections. In infants, water in the larynx can
produce prolonged apnea. The typical response to water, however, in the normal
conscious adult is vigorous coughing. It has been suggested that laryngeal reflexes may
be implicated in the pathogenesis of sudden infant death syndrome, because respiratory
reflex pathways go through a process of maturation in infancy that make laryngospasm
and reflex apnea much more likely to occur during the interval of peak incidence of
sudden infant death syndrome.
CIRCULATORY REFLEXES
Stimulation of the larynx can produce changes in heart rate and blood pressure. This
effect is most noticeable during induction of general anesthesia in response to
endotracheal intubation. It may also occur in natural circumstances such as obstructive
sleep apnea. When upper airway patency is not maintained during sleep, the resulting
increase in negative airway pressure can stimulate receptors in the larynx so strongly that
cardiac arrhythmias occur. The direct result of laryngeal stimulation on blood pressure is
hypertension. However, if laryngeal stimulation produces significant bradycardia or
ectopy, the indirect result can be hypotension.
The pathways responsible for mediating cardiovascular responses to laryngeal
stimulation are not clearly understood. The afferent limb is the superior laryngeal nerve.
Transection of the superior laryngeal nerve abolishes cardiovascular responses to
laryngeal stimulation, and electrical stimulation of this nerve affects heart rate and blood
pressure. The efferent limb for bradycardia is clearly the vagus nerve, but the efferent
limb for blood pressure elevation is not known. Intervening central connections have yet
to be identified, but there is evidence that sympathetic response to laryngeal stimulation
may be mediated through central respiratory control mechanisms. Recordings from
cervical sympathetic roots in the neck have documented phasic activity with breathing,
and this activity is suppressed by electrical stimulation of the superior laryngeal nerve.
SPEECH
The human voice results from the coordinated interaction of the larynx, lungs,
diaphragm, abdominal muscles, throat, neck muscles, lips, tongue, buccinators, and soft
palate. Speech consists of three component processes: phonation, resonance, and
articulation. Phonation is the generation of sound by vibration of the vocal folds.
Resonance is the induction of vibration of the rest of the vocal tract to modulate and
amplify laryngeal output. Articulation is the shaping of the voice into the words that
characterize human speech.
Phonation
Sound is produced by the larynx when expiratory airflow induces vibration of free edges
of the vocal folds as a result of the interaction of aerodynamic and myoelastic forces.
Five conditions must be met to support normal phonation: appropriate vocal fold
approximation, adequate expiratory force, sufficient vibratory capacity of the vocal folds,
favorable vocal fold contour, and volitional control of vocal fold length and tension. Just
before phonation, the vocal folds are approximated in the midline. Exhalation then causes
subglottic pressure to rise until the vocal folds are pushed apart. This separation produces
a rapid decrease in subglottic pressure. The vocal folds then return to the midline as a
result of sudden decrease in pressure, elastic forces in the vocal fold, and the Bernoulli
effect. Pressure in the trachea builds once more, and the cycle is repeated. During modal
phonation, the vocal fold essentially vibrates as two masses, with the upper edge lagging
behind the lower edge. This results in a traveling wave, from caudal to rostral, known as
the mucosal wave. In falsetto mode, the vocal fold is thinner and vibrates as a single
mass; therefore the mucosal wave is absent.
Vocal fold position is a critical factor in phonation. When the vocal folds are loosely
approximated, the mucosa can easily swing open to produce wide fluctuations in
pressure. If the vocal folds are tightly compressed, more expiratory effort is required to
initiate and sustain phonation. If a gap exists between the vocal folds, efficiency is
markedly reduced and a higher airflow is required to induce vibration. The resulting
voice is breathy, and duration of phonation is shortened. With a wide gap, the airflow
requirement exceeds the expiratory capacity, and the voice may dwindle to a whisper.
In normal conversational speech, the driving force for phonation is passive exhalation,
the release of energy stored in the rib cage and diaphragm. Deeper inspiration stores more
energy and therefore permits louder and longer phonation. Contraction of abdominal and
intercostal muscles provides additional expiratory force during greater phonatory efforts
such as singing or shouting. An increase in perceived loudness of phonation during
singing can be achieved by a technique known as vibrato: Expiratory effort is usually
cyclically varied to superimpose slower frequency pressure changes in the vocal output.
The capacity of the vocal folds to vibrate periodically depends on the homogeneity and
flexibility of the mucosa and on the integrity of the lamina propria. Edema, which
increases the impedance of the submucosa, impairs vibration. Trauma, infection, or
surgery can produce scars that tether the epithelium to the underlying muscle and block
the normal propagation of mucosal waves.
The surface contour of the vocal folds determines the shape of the glottal tract. To
support normal phonation, the medial surfaces of the vibratory portions of the vocal folds
must be roughly parallel. If the vocal muscle is atrophic, then the medial surface is
concave rather than convex, resulting in a convergent glottis, which is unfavorable for
phonation.
Changes in vocal fold length and tension influence the fundamental frequency of
vibration of the vocal folds to produce dynamic inflections of the voice. Frequency can
also be controlled by changing the thickness of the fold or by limiting the length of the
vocal fold segment that participates in vibration. The physical properties of a larynx
determine the range of pitches it can produce. The small larynx of a child has a higher
pitch range than the larger larynx of an adult. Young adult males, with longer and heavier
vocal folds and a deeper supraglottis, produce the lowest human pitches. In males during
puberty, the rapid increase in the size of the larynx often outstrips the capacity for
adaptation, resulting in frequent sudden pitch changes. Size is not the only determinant of
pitch range, however, because ossification of the thyroid cartilage with increasing age
contributes to elevation of pitch.
Many attempts have been made to model how vocal cord vibratory movements relate to
global air flow and pressure changes. Recently, a system has been reported that uses
simultaneous aerodynamic and calibrated videostroboscopic measures that allow these
phenomena to be studied in human subjects during phonation (10). Early reports indicate
that this technique has sufficient utility to enhance our understanding of normal and
abnormal vocal fold vibratory patterns.
Another new technique that shows great promise is videokymography (11). Although
stroboscopy is useful in observing stable and regular vocal fold vibration, it does not
allow study and reliable description of irregular vibrations. Videokymography provides
50 to 60 images per second in the standard mode and 8,000 images per second in the
high-speed mode. Vocal fold vibrations in pathologic conditions can be assessed for left-
right asymmetries, open quotient differences along the glottis, and abnormal waves and
movements of the fold mucosa (12).
Resonance
The sound output of the isolated larynx in no way resembles the human voice. Phonatory
output is modulated by resonance, the induction of vibration in the chest, pharynx, and
head with selective amplification of certain component frequencies. Resonance not only
gives the voice its characteristic acoustic pattern but can also amplify the voice. Vocal
training, for singing and acting or public speaking, concentrates heavily on refining and
maximizing resonance, so that the loudest and most pleasing sound can be produced with
the least amount of strain or pressure on the larynx. Resonance is controlled by altering
the shape and volume of the pharynx, by raising or lowering the larynx, by moving
tongue or jaw position, or by varying the amount of sound transmission through the
nasopharynx and nose.
Articulation
The formation of consonants and vowels is largely controlled by the lips, tongue, palate,
and pharynx. The larynx also participates in articulation, by coordinating the beginnings
and endings of phonation to coordinate with upper articulators, producing voiced and
unvoiced sounds.
Sensory Input to Speech Control
One of the primary mechanisms for controlling phonatory output during speech is
auditory feedback. However, when we speak or sing, we do not simply make a random
sound and then adjust the pitch and quality; we preset the vocal tract for the intended
sound. This skill, learned very early in life, uses cues that are largely unconscious. Other
evidence for the involvement of nonauditory cues in voice control is the ability of deaf
patients to maintain fairly normal speech patterns. Well-trained singers are able to
perform with good control of pitch and loudness even when they cannot hear their own
voices. Tactile sensation of induced vibration in the face, throat, and chest is important to
the trained singer. The degree to which receptors in the larynx influence vocal control is
not known. Stimuli such as contact of mucosal surfaces, air pressure, stretch of joint
capsules, and tension in muscles are indicators of laryngeal posture and expiratory effort
and can be important in speech control.

HIGHLIGHTS
The human upper airway is distinguished from that of all other
mammals by the descent of the larynx in early development,
which abolishes the separation of channels for respiration and
deglutition.
Patency of the upper airway during breathing depends on active
contraction of muscles that dilate the pharynx and open the
larynx.
Vocal fold motion is controlled by muscles that act on the
arytenoid.
Tight laryngeal closure is required for the production of an
effective cough.
The larynx plays a role in controlling the rate of breathing by
controlling the rate of airflow into and out of the lungs.
Stimulation of the larynx can result in laryngospasm, breathing
changes, bradycardia, or hypotension.
Human speech has three components: phonation (sound
production), resonance (amplification and filtering of sound),
and articulation (formation of words).
The mucosal cover of the vocal fold is highly specialized for
phonatory vibration.
The pitch of the voice is controlled by changes in length and
tension of the vocal folds.
The sound of the human voice is greatly determined by the
resonance of the upper vocal tract.
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5. Hirano M. Structure and vibratory behavior of the vocal folds. In: Sawashima M, Cooper FS, eds.
Dynamic aspects of speech production. Tokyo: University of Tokyo Press, 1977:13.
6. Sato K. Reticular fibers in the vocal fold mucosa. Ann Otol Rhinol Laryngol 1998;107:10231028.
7. Sant'Ambrogio G, Mathew OP, Fisher JT, et al. Laryngeal receptors responding to transmural
pressure, airflow and local muscle activity. Respir Physiol 1983;54:317.
8. Sant'Ambrogio FB, Mathew O, Clark WD, et al. Laryngeal influences on breathing pattern and
posterior cricoarytenoid muscle activity. J Appl Physiol 1985;58:12981304.
9. Aviv JE, Martin JH, Kim T, et al. Laryngopharyngeal sensory discriminating testing and the
laryngeal adductor reflex. Ann Otol Rhinol Laryngol 1999;108:725730.
10. Kobler JB, Hillman RE, Zeitels SM, et al. Assessment of vocal function using simultaneous
aerodynamic and calibrated videostroboscopic measures. Ann Otol Rhinol Laryngol
1998;107:477485.
11. Schutte HK, Svec JG, Sram F. First results of clinical appli-cation of videokymography.
Laryngoscope 1998;108[8 Pt 1]:12061210.
12. Sung MW, Kim KH, Koh TY, et al. Videostrobokymography: a new method for the quantitative
analysis of vocal fold vibration. Laryngoscope 1999;109:18591863.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

43 UPPER DIGESTIVE TRACT EVALUATION AND IMAGING
Head & Neck SurgeryOtolaryngology
43




UPPER DIGESTIVE TRACT EVALUATION AND
IMAGING
HASKINS K. KASHIMA
ROBERT W. GAYLER

H.K. Kashima: Departments of OtolaryngologyHead and Neck Surgery and Oncology, The Johns
Hopkins Medical Institutions, Baltimore, Maryland.
R.W. Gayler: Department of Radiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland.

Clinical Examination
Radiologic Examination
Common Diseases
Conclusion
Chapter References
The objectives in evaluation and management of dysphagia are a recognition of the
clinical problem, the assessment of the components of normal swallowing function (the
inventory), and development and execution of the management plan.
Safe and effective swallowing is one of three important functions performed by the
competent throat. The competent throat concept recognizes that respiration, deglutition,
and phonation are the three essential primary functions that are performed to perfection in
the healthy throat. Dysfunction of any single function usually is accompanied by adjusted
performance of the remaining functions. Hence, defective performance of any single
function signals the need to investigate the remaining functions and recognize an occult
disorder. It also follows that restoration or correction of any single dysfunction is
achieved at some expense to the remaining throat functions. For example, bilateral vocal
fold paralysis results in inspiratory flow rate limitation, manifested by stridor and cough,
the latter resulting from laryngeal penetration by the liquid bolus. Restoration of airway
by repositioning one of the nonmoving vocal folds will improve the airway at the expense
of the voice, which becomes hoarse.
Three phases are recognized in normal swallow function: oral, pharyngeal, and
esophageal. During the oral phase, the selected bolus is ingested, prepared (mastication),
and modified (lubrication) for delivery from the oral cavity into the pharynx; the first
phase of swallow is under voluntary control and is initiated, paused, and restarted at will.
In the pharyngeal phase, the bolus is delivered through the oropharynx and hypopharynx
in a compacted manner and presented to and through the pharyngoesophageal junction
into the esophagus. The pharyngeal phase comprises at least five distinct tasks that are
performed swiftly in a synchronized manner such that (a) the bolus is prevented from
entering the nasopharynx (by the combined actions of palatal elevation and superior
pharyngeal constrictor contraction); (b) the larynx rises, simultaneously with (c)
retroflexion of the epiglottis and vocal fold closure, which prohibit bolus entry into the
larynx or airway; (d) synchronized contraction of the middle and inferior pharyngeal
constrictors assist in bolus movement; and (e) synchronized relaxation of the
cricopharyngeal muscle facilitates passage of the bolus from the pharynx into the
esophagus. The oropharyngeal phase of swallow is totally involuntary and cannot be
interrupted and restarted once initiated. The esophageal phase of swallowing is
involuntary and begins with relaxation of the cricopharyngeal muscle and coincident
elevation of the larynx, which permit the bolus to enter the esophagus and to be carried
distally to and through the lower esophageal sphincter by peristaltic contraction of the
esophageal smooth muscles.
The task for the otolaryngologist is first to recognize that disordered swallowing is
present and to identify the components and severity of the dysfunction. The dysphagia
may be constant or episodic, stable, progressive, or relapsing and may have variable
severity depending on the nature of the boluswhether solid, liquid, or particulate (such
as with medications). Pain and psychotropic medications may adversely and significantly
alter swallow function (1).
CLINICAL EXAMINATION
The physical examination is a singularly important opportunity to evaluate swallowing
function and to identify the specific defective components. The mental status, body
posture, and voice quality are noted. The wet voice is due to failure to clear the
hypopharynx of retained or entrapped secretions, which may penetrate the larynx and
induce a coughing spasm and interrupt swallow effort. Drooling indicates failure to
manage oral secretions due to either labial incompetence or tongue weakness. Slurred
speech or articulation errors suggest the possibility of tongue palsy, unilateral or bilateral.
Wheezing respiration and accompanying dyspnea accompany dysphagia that may be
subclinical and overlooked.
Inspection and palpation of the tongue test its strength against the examiner's finger and
often unmask fibrillation and fasciculation of one or both sides of the tongue, identifying
hypoglossal paresis or paralysis. Palatal elevation and sensation and inspection of the
posterior oropharyngeal mucosa on phonation should reveal a bilaterally balanced and
brisk movement of these parts. Consistent lateral movement of the posterior
oropharyngeal mucosa indicates motor weakness opposite to the direction of the mucous
membrane movement. During nasopharyngoscopy and hypopharyngoscopy, high-pitched
phonation produces contraction of the superior pharyngeal constrictor muscles; unilateral
constrictor muscle weakness and/or lateral movement of the posterior pharyngeal mucosa
is a clue that sensorimotor dysfunction of the ninth and tenth cranial nerves may be
present.
Laryngeal examination may be particularly difficult in individuals with entrapped
secretions filling the hypopharynx and laryngeal vestibule. Motor function of the vocal
folds is often difficult to evaluate; it is helpful to examine the vocal folds during variable-
pitch phonation and during whispering, loud voicing, and inspiratory phonation.
Inspection of the arytenoids will disclose unilateral motion impairment in either the
gliding or rotating movement; frank joint fixation must not be overlooked. Appearance of
the posterior laryngeal mucosa is abnormal in certain patients with active
gastroesophageal reflux. Heightened erythema surrounding and overlying the arytenoids
may be accompanied by edema, loss of corrugation of the interarytenoid mucosa, and
inability to visualize the blanched transverse mucosal fold, which are additional clues
suggestive of gastroesophageal reflux. The severity of the erythema, edema, and the
prominence of the vessel patterns can be used to grade severity of reflux.
Hypopharyngeal examination provides important insight about pharyngoesophageal
dysfunction. Thick mucoid secretions indicate standing accumulations, often due to
paralysis or adynamic muscle function. Foamy secretion in the piriform sinuses and
laryngeal vestibule indicates turbulence due to anatomic obstruction such as that
attributable to a nonrelaxing cricopharyngeal muscle, stricture due to scarring, or a
nonyielding tumor or impacted foreign body.
In the nonanesthetized throat, a 5-mL sip of mint-flavored methylene blue solution will
confirm the presence of obstruction or retention of secretions and discriminate functional
from structural obstruction; staining of the laryngeal vestibule, vocal folds, and trachea
without inducing cough response suggests that dysfunction may be of long standing.
The cricopharyngeus (upper esophageal sphincter) has a normal resting tone, which is
increased during inspiration and relaxed during bolus passage. This cyclic pattern is
disturbed when there is intrinsic neuromuscular dysfunction causing spasm or when
dyskinesia or reactive hypertonicity is due to inflammation, fibrosis, or certain connective
tissue or neurologic disorders. A hypertonic and imperfectly relaxing cricopharyngeus
may also be observed in response to acid reflux. Status of the pharyngoesophageal
segment is conveniently evaluated by noting the presence of retained secretions.
Secretions that fail to clear after swallow effort is attributable to a neurologic disorder
when thickened and mucoid and to a structural disorder, stenosis or pouch, when the
secretions are frothy or foamy.
In the esophagus, normal function is manifested by antegrade peristalsis; this may be
disrupted due to spasm, aperistalsis, or other dyskinetic contractions. Abnormal function
may be asymptomatic, although inflammation and muscular spasms are often recognized
by sensation of substernal pressure or discomfort. The esophagogastric (lower)
esophageal sphincter has a normal resting tone with relaxation coincident with bolus
arrival to facilitate its passage. Dysfunction is characterized by excessive tone, spasm, or
stenosis due to an intramural lesion or fibrosis. A hypotonic lower esophageal sphincter is
at risk for permitting acid reflux into the esophagus. The symptoms are substernal
discomfort, pain, and heartburn.
Palpation of the neck should include an evaluation of passive mobility of the
laryngotrachea, presence of cricovertebral crepitus (absent in postcricoid mass lesions),
and comparative muscle tone of the sternomastoid and trapezius muscles (eleventh
cranial nerve). The examining finger on the thyroid notch during swallow will indicate
whether the larynx rises with deglutition. Absence of an upward movement indicates
fixation of the larynx due to inflammation, tumor, or paralysis.
The report of gurgling or other extraneous noise in the neck or palpable crepitus in the
same zone alerts to the possibility of a Zenker diverticulum or other pouch. The anterior
face of the cervical vertebrae can be palpated by gently displacing the larynx and trachea
to the side, and in certain patients, the lateral displacement and rotation of the larynx
permit gentle palpation of the cricoarytenoid joint and can corroborate the clinical
suspicion of a cricoarytenoid inflammation or arthrodesis.
This detailed sensorimotor inventory of the oropharyngeal parts is integrated with other
findings from the standard otolaryngologic examination of the head and neck. Thyroid
gland or other abnormal neck mass and other cranial neuropathies, including facial
sensation, Horner syndrome, or other unexpected findings, help to focus and expand the
etiologic possibilities that should be included in the comprehensive dysphagia evaluation.
On the basis of the medical history and physical examination findings, dynamic
radiographic imaging studies (e.g., cine or video swallowing examinations) (2), computed
tomography, and magnetic resonance imaging examinations are requested with specific
questions to be answered. When appropriate, endoscopic examination is performed to
complete the evaluation and plan the management (3).
Recently, the concept of combining flexible endoscopic evaluation of swallowing with
sensory testing (FEESST) has been described by Aviv et al. (4). This approach allows the
traditional visual evaluation of swallowing plus delivering air pulse stimuli to the mucosa
innervated by the superior laryngeal nerve. Specific abnormalities of deglutition can be
assessed safely in patients with chronic neurologic disease or strokes using this
technique. It is also useful in overcoming the problems of interobserver variability
encountered when videoendoscopy is used above (5).
RADIOLOGIC EXAMINATION
The radiologic examination of the patient with impaired swallowing is guided by the
medical history and physical findings, which are communicated by the clinician to the
radiologist. The first radiologic decision relates to selection of the imaging examination,
whether to select fluoroscopy with still (spot) radiographs, fluoroscopy with dynamic
recording (usually videotape), computed tomography, or nuclear medicine imaging.
Dynamic fluoroscopic recording is the most useful overview examination (6).
The second decision is selection of the contrast to be used. There are various contrast
agents in first look options, depending on the most likely diagnostic choices. The
choice of small volumes of contrast media or free swallow is influenced by the history.
The details of these decisions will not be reviewed here but are noted to reinforce the
importance of communication, either written or verbal, between the referring clinician
and the radiologist.
Examination of the usual patient is done first in the upright position. Preliminary films
of the neck and chest provide important background information, such as prior surgery,
airway narrowing, soft-tissue air, air in the esophagus, pneumonia, or mediastinal
adenopathy, to list some of the important findings.
When there is concern about esophageal obstruction, a small volume (5 mL) of barium
can be followed fluoroscopically from the mouth into the stomach or to the point of
obstruction. If there is obstruction, its location, anatomic dimensions, and deviations are
documented and characterized with or without additional barium, as needed. If there is no
or minimal obstruction, the examination can be continued in a more logical top to bottom
way.
When there is concern about aspiration, a small amount (3 mL) of thin barium may be
given with the patient in the lateral position and observation of the pharynx and larynx
done. Thin barium does not coat well but is easily coughed up if aspirated. Small
quantities of aspiration are more easily seen in the lateral than in the frontal position. If
there is concern about extravasation from a fistula or surgical anastomoses, barium may
not be the first choice of contrast agents, because it is not absorbed from soft tissues and
may form a nidus for infection. Water-soluble contrast is safe in the tissues but is usually
in a hyperosmolar concentration and can cause pulmonary edema if it reaches the
peripheral airway. The details of these special situations are mentioned to emphasize the
importance of good physician dialogue to ensure maximum yield from each examination.
Simulated foods, such as applesauce mixed with barium, graham cracker with barium, or
barium tablets, may be used as the clinical condition warrants. A portion of the
examination is typically done with the patient horizontal, so that the quality of esophageal
peristalsis can be observed rather than simply the effects of gravity. A pad may be placed
under the abdomen with the patient prone to increase intraabdominal pressure. Rapid
multiple swallowing can be useful to stress the pharynx or esophagus. These examination
alternatives are carefully selected to minimize the amount of radiation exposure
particularly for patients who require repeated examinations.
It is generally believed that the modified barium swallow test and endoscopic evaluations
of swallowing are the most comprehensive studies for evaluating and managing patients
with severe dysphagia and aspiration. A recent report compares these studies with
FEESST in terms of preventing pneumonia. In this study, FEESST appeared to be a
slightly better technique for managing these patients in terms of preventing pneumonia
and had the additional advantages of lower cost plus the portability of the FEESST
equipment (7).
COMMON DISEASES
Reflux esophagitis and its associated side effects and complications are common causes
of dysphagia (Fig. 43.1 and Fig. 43.2). These patients are examined for atypical
symptoms or to assess and treat complications of reflux. Reflux occurs episodically but
becomes a problem when it occurs on a frequent basis. It occurs when the lower
esophageal sphincter is incompetent for any reason; hiatal hernia is not required for
reflux to occur (Fig. 43.3 and Fig. 43.4). The mild manifestations of reflux are pain;
spasm, ulcer, and stricture are more serious consequences of esophagitis and may result
in delayed transit of food. Dynamic imaging is very helpful in initial diagnosis and in
evaluating the effect of treatment. Symptoms of food holdup may be accurately
localized by the patient, but it is common for the patient to have sensation of food holdup
in the throat when there is, in fact, holdup of material in the lower esophagus. Therefore,
the symptoms of delayed passage of food through the throat requires a careful
radiographic examination of the pharynx and entire esophagus.

FIGURE 43.1. Reflux esophagitis with stricture at
gastroesophageal junction. The left image shows a small
hiatal hernia (triangle), narrow gastroesophageal junction
(arrow), and nonpropulsive waves in the esophagus.



FIGURE 43.2. Chronic reflux with small ulcerations and
mucosal distortion. The open arrows point to a row of
small ulcers.



FIGURE 43.3. Scleroderma. Decreased motility, chronic
reflux due to incompetent lower esophageal sphincter,
and stricture of the distal esophagus. Arrowhead points to
stricture in middle image.



FIGURE 43.4. Achalasia. The lower esophageal
sphincter is narrowed, the esophagus is dilated to 6 to 7
cm wide, and there is an air-fluid level 16 cm above the
sphincter. Arrow points to narrowed sphincter.



Hypertrophy of the cricopharyngeal muscle is commonly seen in patients with long-
standing reflux. Cricopharyngeal hypertrophy narrows the lumen and causes solid-food
dysphagia. A diverticulum may form from the area of muscle thinning just superior to the
cricopharyngeal muscle (Zenker diverticulum). Such diverticula typically retain fluid and
food particles (often medications), which may reenter the pharynx and may be aspirated,
in as much as the fluid is entrapped just above the laryngeal inlet and out of synchrony
with swallowing. Cricopharyngeal hypertrophy may be seen in neurologic or
neuromuscular disorders, but in our experience it is more often observed in conjunction
with gastroesophageal reflux.
Esophagitis from causes other than reflux include opportunistic infection (e.g., Candida,
herpes, cytomegalovirus) and chemical injury, including some medications (Fig. 43.5).
Strictures may occur from chemical (e.g., lye) or traumatic injury.

FIGURE 43.5. Candidiasis. Multiple ulcerations and
nodularity over a long segment. The patient was
immunocompromised.



Cerebrovascular accidents are a common cause of dysphagia. These patients are usually
seen in an acute, semiacute, or chronic phase to assess the need for tube alimentation or
intravascular support and to assess progress and prognosis. The principal questions in this
setting relate to oral and pharyngeal phases of swallowing. The examination is typically
done in the supine or semiupright position, whichever the patient's condition permits.
Small quantities of thin barium or soft mixture (barium with applesauce) can be given
with care. Availability of suction is essential when examining these patients. Dynamic
recording is very important, because the entire examination may be limited to one or two
swallows if the patient aspirates significantly (Fig. 43.6).

FIGURE 43.6. Familial dystonia. The upper portion of
the cervical spine has a lordotic curve; the lower portion
is straight. There is disk narrowing at C5-6 and C6-7 with
spurring. The soft palate is weak, and there is
nasopharyngeal escape (arrowhead) during swallowing.
The pharyngeal discoordination permits aspiration, with
barium coating. The vocal folds (arrow) are coated with
aspirated barium.



In preoperative assessment of patients with laryngopharyngeal tumors, assessment of
mobility of involved structures and screening for synchronous tumors of the esophagus is
done. In this setting, maneuvers to distend the pharynx are informative.
In suspected or known cancer of the esophagus, contrast examination documents the
location and size of the lesion and the presence of fistulae. Computed tomography is
typically done in these patients to assess deep tissue invasion and to look for a
mediastinal adenopathy (Fig. 43.7 and Fig. 43.8).

FIGURE 43.7. A: Cancer of mid-esophagus. There is a
shelf at the upper and lower extent, with extensive
irregularities in the tumor mass. B: Computed
tomography through the cancer shows thickening of the
esophageal wall. Intravenous contrast media was used,
with vascular opacification.



FIGURE 43.8. Piriform sinus squamous cancer. In the
frontal view, the arrow indicates the upper portion of the
mass. In the lateral view, the arrow indicates the lower
portion of the mass.



Postoperative assessments may be done after oral, laryngeal or pharyngeal, and
esophageal surgeries to look for any extravasation and to determine the patency of the
food passageway. The details of these examinations vary according to the purpose of the
examination (Fig. 43.9).

FIGURE 43.9. Postlaryngectomy. There is tapered
narrowing anterior to C-5.



In summary, radiologic examination provides both anatomic and functional information
about the oral, pharyngeal, and esophageal phases of swallowing. Examination may be
done during an initial phase of evaluation, preoperatively, or in follow-up. To provide the
most information with minimal patient risk, the examination must be tailored to the
individual patient's circumstances, and communication between the clinician and
radiologist should precede the examination. Joint review of the images ensures maximum
benefit and utilization of the radiologic findings.
CONCLUSION
Among the steadily increasing geriatric population (i.e., 75 years and older), swallowing-
related disorders constitute a significant impairment that often requires adjustment in
living arrangements and the activities of daily living (8). Among hospitalized patients
recovering from a wide variety of medical and surgical disorders, the inability to maintain
nutritional needs by oral feeding can prolong hospitalization or require other adjustments
in postdischarge placements. The increasing use of gastrostomy and jejunostomy
feedings has been a workable and necessary solution but could often be avoided by
identification and correction of occult dysphagia.
The challenge to the otolaryngologist and other physicians is to identify patients with
dysphagia due to selective neurologic deficits among whom improvement in quality of
life can be achieved by targeted therapies or imaginative and novel interventions. The
objective of a comprehensive clinical and ra-diographic evaluation such as described
intends, in part, toidentify and correct critical deficiencies in components of swallowing.
For example, cricopharyngeal myotomy has had an irregular track record. The
recognition of defective laryngeal elevation led to the development of a technique to
combine restoration of dynamic suspension-elevation of the larynx to cricopharyngeal
myotomy that has restored effective swallowing in several patients. Dysphagia evaluation
with detailed analysis of the individual components in the swallowing act is one manner
by which to recognize certain motor deficiencies for which rehabilitative therapy or a
surgical option can be fruitful.
Swallowing impairment may be the earliest symptom of a chronically debilitating
neurologic disease, malignant neoplasm, connective tissue disorders, or other morbidities.
Such secondary dysphagia attributable to neurologic, neoplastic, or paraneoplastic
syndromes requires careful characterization so that optimum management alternatives
can be identified.
The goal of the detailed dysphagia evaluation is to determine the underlying or major
contributing factor whose correction could improve the management and correct certain
forms of dysphagia. With the increasing utilization of microinvasive technologies and
imaginative application of assistive devices, the dysphagic patient benefits.

HIGHLIGHTS
The competent throat concept recognizes the interdependence
of the three essential functions: respiration, deglutition, and
phonation.
Impaired performance in any function is accompanied by
altered performance in the second and third functions.
Surgical restoration of any function is achieved at the expense
of altering performance in the second and third functions.
The bolus is organized, lubricated, and prepared for delivery in
the oral phase.
The pharyngeal phase is involuntary and swift and is composed
of at least five recognizable actions that guide the bolus from
the faucial arch to and through the pharyngoesophageal
segment.
Impaired swallow can be attributed to one of three
dysfunctions: obstruction, bolus misdirection, or fragmentation.
The medical history is focused to detect symptoms resulting
from obstruction, misdirection, or fragmentation of a bolus.
The pharyngeal examination is directed to evaluating each of
the five component actions in the pharyngeal phase of
swallowing.
The radiographic examination, particularly the cine or video
pharyngoesophagogram, is an individualized diagnostic
examination that corroborates and elaborates abnormalities
identified in the history and physical examination.
Optimal dysphagia management depends on an individualized
plan derived from analysis of the detailed history, targeted
physical examination, and focused collaborative examinations.
The patience and determination of the patient must be matched
by that of the physician and therapist to achieve maximal
benefit.
CHAPTER REFERENCES
1. Logemann JA. Swallowing physiology and pathophysiology. Otolaryngol Clin North Am
1988;21:613.
2. Bastian RW. Videoendoscopic evaluation of dysphagia in an office setting. In: Clinical geriatric
otorhinolaryngology, 2nd ed. Philadelphia: B.C. Decker, 1992:1320.
3. Broniatowski M, Sonies BC, Rubin JS, et al. Current evaluation and treatment of patients with
swallowing disorders. Otolaryngol Head Neck Surg 1999;120:464473.
4. Aviv JE, Kaplan ST, Thomson JE, et al. The safety of flexible endoscopic evaluation of
swallowing with sensory testing (FEESST): an analysis of 500 consecutive evaluations.
Dysphagia 2000;15:3944.
5. Logemann JA, Rademaker AW, Pauloski BR, et al. Interobserver agreement on normal
swallowing physiology as viewed by videoendoscopy. Folia Phoniatr Logoped 1999;51:9198.
6. Robbins J, Coyle J, Rosenbek J, et al. Differentiation of normal and abnormal airway protection
during swallowing using the penetration-aspiration scale. Dysphagia 1999;14:228232.
7. Aviv JE. Prospective, randomized outcome study of endoscopy versus modified barium swallow
in patients with dysphagia. Laryngoscope 2000;110:563574.
8. Yokoyama M, Mitomi N, Tetsuka K, et al. Role of laryngeal movement and effect of aging on
swallowing pressure in the pharynx and upper esophageal sphincter. Laryngoscope 2000;110:434
439.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

44 AIRWAY EVALUATION AND IMAGING
Head & Neck SurgeryOtolaryngology
44




AIRWAY EVALUATION AND IMAGING
ROBERT H. MILLER
ROBERT C. WANG
ANDREW J. NEMECHEK

R.H. Miller: Office of the Dean of Medicine, University of Nevada School of Medicine, Las Vegas,
Nevada.
R.C. Wang: Division of Otolaryngology, Department of Surgery, University of Nevada Medical School,
Las Vegas, Nevada.
A.J. Nemechek: Department of OtolaryngologyHead and Neck Surgery, Tulane University School of
Medicine, New Orleans, Louisiana.


History
Physical Examination
Differential Diagnosis
Physiologic Testing
Imaging
Plain-Film Radiography
Fluoroscopy
Contrast Radiography
Polytomography
Ultrasonography
Arteriography
Computed Tomography
Magnetic Resonance Imaging
Endoscopic Assessment
Diagnostic Endoscopy
Flexible Laryngoscopy and Bronchoscopy
Rigid Laryngoscopy and Bronchoscopy
Complications
The Future
Chapter References
Head and neck surgeons often evaluate patients with upper airway dysfunction. Detecting
upper airway dysfunction in cases of acute fulminant processes such as epiglottitis may
be obvious on simple inspection of the patient, but more subtle or chronic forms of
airway dysfunction may be very difficult to diagnose. Complete evaluation of the airway
demands a thorough knowledge of the complex anatomy and physiology of the upper and
lower respiratory tract. Combining this knowledge with the history, physical
examination, radiographic imaging, endoscopy, and laboratory and physiologic testing,
the head and neck surgeon can generate a comprehensive differential diagnosis and
formulate an appropriate treatment strategy.
Any upper airway assessment must include evaluation of its three major functions:
protection, respiration, and phonation. Deglutition, a very closely associated function of
the upper aerodigestive tract, is also evaluated. Respiration is a coordinated muscular
effort to enlarge the airway and expand the thoracic cavity, thus promoting air entrance
for gaseous exchange at the alveolar level. Protection of the airway occurs at multiple
levels and includes a series of sphincteric mechanisms (oral, pharyngeal, and laryngeal),
a cough reflex for expulsion of secretions and foreign bodies, and the cessation of
respiration. Phonation requires normal laryngeal function, allowing freely mobile vocal
cords that approximate and vibrate unimpeded. The oral cavity and pharynx must also
function normally to attenuate and resonate sound energy produced by the larynx.
Deglutition involves the action of oral, pharyngeal, laryngeal, and esophageal
musculature to coordinate cessation of respiration, propulsion of the food bolus, and
closure of the laryngeal inlet.
HISTORY
A thorough history will direct the diagnostic workup that follows, which may be
invasive, extensive, and expensive. Questions about symptomatology, especially as it
pertains to respiration, protection of airway, phonation, and deglutition, should include
assessment of the timing, frequency, severity, and characterization of these symptoms
and their association with other symptoms.
The predominant symptoms of airway dysfunction are dyspnea, cough, hoarseness,
dysphagia, and odynophagia. The common signs of airway dysfunction include stridor,
respiratory distress, and possibly aspiration.
Stridor is the harsh sound produced by turbulent airflow through the upper airway. This
turbulence is caused by a narrowing of the airway. The character of stridor should be
described in terms of the respiratory cycle, to aid in the identification of the site of
obstruction. Typically, inspiratory stridor is characteristic of an extrathoracic airway
lesion (usually supraglottic), whereas expiratory stridor is heard with an intrathoracic
lesion. Biphasic stridor, heard during inspiration and expiration, is present with more
critical lesions that may exist at any region of the upper airway, although they are very
common in the subglottic and cervical trachea. The time at onset of stridor should be
noted and its frequency and duration and the presence of cyanosis. Associations with
feeding, agitation, exercise, sleep, and position changes should also be elicited. The
degree of dysp-nea and anxiety of the patient may help determine the rapidity of onset of
the obstruction, because slowly progressive obstructions are compensated for much more
easily than rapidly progressive ones.
Cough is one of the normal protective mechanisms of the respiratory tract and is
considered a symptom of a pathologic process when it is persistent, occurs with increased
frequency, or is associated with productive secretions. Cough consistently associated with
deglutition may indicate aspiration. Occasional minor aspiration can be seen in normal
individuals, but it is usually a sign of a lesion (neurologic or mechanical) that prevents
closure of the larynx or obstructs the upper digestive tract with subsequent soilage of the
airway. In children, the primary causes of cough change as the patient gets older. These
include aberrant great vessels, cough variant asthma, gastroesophageal reflux, sinusitis,
and psychogenic causes (1).
Hoarseness may be the first sign of airway dysfunction, because even the smallest true
vocal cord lesion can produce alterations in voice. An important distinction is whether the
hoarseness is constant or intermittent. Constant progressive hoarseness often indicates a
more serious disease process, such as laryngeal carcinoma or recurrent respiratory
papillomatosis. Intermittent hoarseness is usually associated with more benign processes
such as vocal abuse, reflux laryngitis, or laryngitis secondary to postnasal drip.
Dysphagia is difficulty in swallowing, and odynophagia is pain on swallowing. Because
of the anatomic proximity and numerous neurologic interrelations with the upper
digestive tract, dysphagia and odynophagia are common features of upper airway
dysfunction. A history of vomiting and nasopharyngeal reflux may also be elicited. Other
symptoms commonly elicited from the patient with airway dysfunction include nasal
obstruction, mouth breathing, hemoptysis, referred otalgia, and the globus phenomenon
(sensation of a lump in the throat). Symptoms of obstructive sleep apnea (daytime
somnolence, snoring, restless sleep, morning headaches) may also be encountered.
A complete medical history is also important, with specific attention directed toward a
history of previous airway inter-ventions (i.e., intubation or tracheotomy), head and neck
or thoracic surgery, trauma, foreign body ingestion/aspiration, hospitalizations for
respiratory distress, dental manipulation, autoimmune disorders, asthma or chronic
obstructive pulmonary disease, granulomatous diseases, neurologic disorders, and
malignancy. A history of tobacco and alcohol abuse and a list of allergies and current
medications (e.g., angiotensin-converting enzyme inhibitors may produce a
nonproductive cough) should also be elicited. Family history, the presence of congenital
anomalies, birth history, growth, and developmental history should be obtained in
pediatric patients.
PHYSICAL EXAMINATION
The upper airway includes the nose, oral cavity, pharynx, larynx, trachea, and bronchi.
All these structures except the trachea and bronchi can be inspected directly by the head
and neck surgeon in the clinic. The patient with suspected upper airway dysfunction
should undergo a complete head and neck examination, including chest auscultation and
neurologic evaluation.
General observation of the patient is the initial component of the physical examination.
The patient should be assessed for the degree of dyspnea, anxiety, and agitation. When
approaching a patient in acute airway distress, particularly a child, the physician must be
cautious: Respiratory arrest may be precipitated by further agitating the patient.
Chest auscultation in the patient with respiratory symptoms may reveal signs of lower
airway disease. Indeed, patients with upper airway dysfunction often also have lower
respiratory tract disease. The differentiation between upper and lower airway disease as
the etiology for respiratory distress may be difficult.
The nasal examination should include evaluation for nasal septal deviation, turbinate
hypertrophy, polyps, signs of infection or inflammation, and mass lesions. The oral cavity
and oropharynx should also be examined for mass lesions, inflammation, and edema
while paying attention to dental hygiene; tenderness of the teeth and gums; symmetry of
the palate, tonsils, and pharynx; and palate and tongue mobility. Bimanual palpation of
the floor of the mouth and the tongue is an invaluable aid for detecting neoplastic and
infectious processes. Inspection and palpation of the neck are performed to search for
thyromegaly, adenopathy, masses, and the symmetry and position of laryngeal and
tracheal cartilages. Neck masses and lymph nodes are described by size, consistency,
location, and fixation in addition to associated signs of erythema, edema, tenderness, and
pulsations. Auscultation of neck masses may reveal the vascular nature of certain lesions
if a bruit is detected.
The larynx, hypopharynx, and nasopharynx are evaluated by indirect mirror examination
in most cases. The rigid 90-degree telescope, an alternative tool for office laryngoscopy,
gives excellent visualization of the larynx and is tolerated better than indirect
laryngoscopy. The rigid laryngeal telescope has a very bright external light source and
excellent optics, making it an ideal instrument for videolaryngoscopy. Flexible
nasolaryngoscopy may be used in patients with a very sensitive gag reflex or for
prolonged visualization of the larynx. It is also the method of choice when evaluating
patients with neurologic diseases of the larynx because it does not interfere with
laryngeal and pharyngeal function.
The nasopharynx is evaluated for patency, the presence of mass lesions, and signs of
inflammation or infection. The larynx and hypopharynx are examined for mucosal
abnormalities, inflammation, edema, or mass lesions along all surfaces, including the
base of the tongue, epiglottis, glottis, and the base of the piriform sinuses. The apices of
the piriform sinuses and the postcricoid area are poorly demonstrated by office
examination, but pooling of secretions and swelling near these areas may be clues to the
presence of disease and the need for further evaluation by direct laryngoscopy. The
larynx is also evaluated for neurologic competence by asking the patient to perform
phonatory maneuvers and coughing. The side and position of an immobile cord and any
rotation of the posterior commissure should be recorded.
The neurologic examination consists of a thorough cranial nerve assessment, a cursory
mental status evaluation (if not already obvious), and determination of cerebellar and
coordination abilities.
DIFFERENTIAL DIAGNOSIS
An accurate differential diagnosis helps direct the workup. A thorough differential
diagnosis is important in diagnosing unusual pathologic processes that otherwise may not
even be considered. A list of diagnoses of upper airway lesions is presented in Table
44.1. This is not a list of all possible diagnoses of upper airway lesions but is intended as
a stimulus for the clinician to consider the differential diagnoses in an ordered format,
namely by anatomic site and pathologic process.

TABLE 44.1. DIAGNOSIS UPPER AIRWAY
OBSTRUCTION



PHYSIOLOGIC TESTING
Common physiologic tests used to assess airway function include polysomnography,
pulmonary function tests with flow-volume loops, laryngeal and pharyngeal
electromyography (EMG), and a host of phonatory tests. Polysomnography is used to
determine the presence and physiologic significance of airway pathology that results in
obstructive sleep apnea syndrome. The site (intrathoracic or extrathoracic) and character
(fixed or variable) of obstructive airway lesions may be determined by pulmonary
function tests with flow-volume loops. Both poly-somnography and flow-volume loops
may be used serially to determine the success of therapeutic endeavors and to observe for
recurrence of pathology. EMG of the laryngeal and pharyngeal musculature may help
locate neural or muscular dysfunction of the upper airway. Numerous tests of phonation
have been devised, and in-depth descriptions of them may be found in speech pathology
texts.
In polysomnography, commonly called a sleep study, multiple physiologic parameters
(EMG, electroencephalography, electrocardiography, electrooculography, nasal and oral
airflow, re-spiratory movements and effort, oxygen saturation levels, sleep position, and
acoustic monitoring) are measured while the subject sleeps to detect airway obstruction
that occurs during sleep, resulting in the sleep apnea syndrome. From these
measurements, the duration and severity of apneic episodes may be determined, as well
as its effects on oxygen desaturation, cardiac rhythm, and ectopy. Chapter 50 offers a
more detailed discussion on obstructive sleep apnea.
In the pulmonary function laboratory, patients breathe into a spirometer to measure the
movement of air through the respiratory tract during the respiratory cycle. These volumes
include the following:
Tidal volume: the volume of air expired or inspired throughout each respiratory
cycle;
Residual volume: the quantity of air that remains in the lungs at the end of a
maximal expiratory effort;
Total lung capacity (TLC): the amount of air contained in the lungs after a
maximal inspiratory effort;
Forced vital capacity: the volume of air that can be forcefully expired after
inspiration to TLC;
Functional residual capacity: the volume of air that remains in the lungs after
quiet expiration;
Forced expiratory volume at 1 second: the volume of air forcefully expired in 1
second after maximal inspiration;
The ratio of forced expiratory volume at 1 second to forced vital capacity (Table
44.2).

TABLE 44.2. SPIROMETRY
MEASUREMENTS



The flow-volume loop is measured during one cycle of forced expiration and forced
inspiration beginning at TLC, exhaling to residual volume, and inhaling back to TLC.
The airflow rate is measured continuously throughout the respiratory cycle and plotted
against the lung volumes, thus obtaining a loop configuration (Fig. 44.1).

FIGURE 44.1. Flow-volume loops. A: Normal. B:
Variable extrathoracic obstruction. C: Variable
intrathoracic obstruction. D: Fixed obstruction.



Flow-volume loops display three characteristic patterns for upper airway obstruction:
variable extrathoracic obstruction, variable intrathoracic obstruction, and fixed
obstruction (may be intrathoracic or extrathoracic). These three patterns can help the
physician assess the site, severity, and characteristic (variable or fixed) of upper airway
obstruction.
Variable extrathoracic obstruction refers to a lesion above the thoracic inlet that
preferentially obstructs the airway during inspiration. This is due to the Venturi principle,
in which gas flowing through a pipe travels faster with less outward pressure, thereby
causing a partial collapse of the narrowed area. This tends to narrow the extrathoracic
airway during inspiration, thus allowing any obstructive lesion to become more
pronounced. This effect is reversed during expiration, which tends to dilate the
extrathoracic airway. Consequently, the flow-volume loop demonstrates a flattening of
the curve's inspiratory component as a result of selective limitation of flow during
inspiration, whereas the curve's expiratory component is unaffected. A typical lesion
demonstrating this characteristic is laryngomalacia.
Variable intrathoracic obstruction refers to a lesion below the thoracic inlet that
selectively obstructs the airway during expiration. During expiration, the pressure in the
thoracic cavity increases, resulting in expulsion of air but also narrowing of the
intrathoracic airways (particularly those that are malacic) and consequently amplifying
the obstructive effects of the lesion. As a result of expansion of the thoracic cavity during
inspiration, the intrathoracic airways are dilated, thus negating the effects of the
obstructing lesion. The flow-volume curve typically demonstrates flattening during the
expiratory phase as a result of diminished expiratory flow rates, whereas the inspiratory
curve is unaffected. Intrathoracic lesions include tracheomalacia, tracheal foreign bodies,
and certain intrinsic or extrinsic mass lesions.
Fixed obstruction refers to any lesion that results in a limitation of flow rates during both
inspiration and expiration. These lesions may be intrathoracic or extrathoracic. This
situation typically occurs with lesions that are either very severe or do not yield to the
pressure changes during inspiration or expiration. The flow-volume loop demonstrates
flattening of both the inspiratory and expiratory phases. This commonly occurs with
infiltrative processes such as malignant neoplasms, sarcoidosis, and tracheal stenosis.
Flow-volume loops may be used to determine if a pathologic respiratory process is of
upper airway origin or of parenchymal origin. They can also be used to determine the
significance of an obstructing lesion. Finally, flow-volume loops are useful to document
responses to therapy directed at supraglottic, glottic, and infraglottic sources of airway
obstruction (2).
Laryngeal and pharyngeal EMG provides information on the status of the motor units of
these areas. A motor unit consists of a muscle and its innervating lower motor neuron.
Techniques have been developed for EMG of all the intrinsic laryngeal muscles and
many of the pharyngeal muscles. Clinically, EMG is useful in the differentiation of
laryngeal paralysis from mechanical fixation of the cricoarytenoid joint and establishment
of the diagnosis of superior laryngeal nerve paralysis. EMG has also been found to be
valuable in differentiating laryngeal joint injuries from neuropathy or myopathy (3).
EMG is useful for estimating the degree of paralysis and prognosis for recovery.
Laryngeal EMG is limited by operator experience, and technical difficulties include
problems with verification of electrode placement, especially in pediatric patients.
Chapter 52 gives a more detailed discussion of laryngeal EMG.
IMAGING
Plain-Film Radiography
Anteroposterior and lateral radiographs of the upper airway obtained using a soft-tissue
protocol are often used as screening examinations for the patient with suspected airway
compromise. Air, a natural agent against the surrounding soft tissues, makes many
important structures easily identifiable, such as the epiglottis, aryepiglottic folds, base of
tongue, glottis, retropharyngeal soft tissues, and the nasopharynx, pharynx, larynx, and
tracheal airways (Fig. 44.2). Radiographs are useful in evaluating pathologic processes
that produce deviation of the airway, such as extrinsic neck masses, processes that
produce circumferential narrowing, and lesions that make an impression on the column of
air within the airway. Lateral neck films should be taken in both inspiration and
expiration.

FIGURE 44.2. Normal soft-tissue lateral x-ray showing
epiglottis (E) and ventricle (V).



Retropharyngeal space processes (infection, abscess, mass) may be detected by these
plain films. Caution must be used in evaluating the retropharyngeal tissues in children,
because films taken during expiration may simulate a mass or abscess. Airway films
should be taken with the head and neck extended and during inspiration. Soft-tissue
thickening greater than one half of the width of the vertebral body at C-3 is considered
pathologic in children, as is greater than 14 mm thickening of prevertebral tissues at C-6.
Narrowing of the airway may be seen in subglottic stenosis, croup, or tracheal stenosis.
Swelling and enlargement of the supraglottic larynx are commonly seen on the lateral
view in cases of acute supraglottitis (epiglottitis). Plain films may be very useful in
identifying and locating radiopaque foreign bodies. Also, plain films have been used
extensively for cephalometric analysis to aid in the treatment of obstructive sleep apnea.
The lateral and anteroposterior chest x-ray film is also a valuable test for the patient with
airway compromise. The chest x-ray film is a good screen for mediastinal and
parenchymal masses. Radiopaque foreign bodies of sufficient size may be seen on plain
chest x-ray films. The presence of nonradiopaque bronchial foreign bodies may be
deduced by other findings on the chest x-ray film. Again, it is imperative to obtain
inspiratory and expiratory chest films. If a bronchial foreign body produces a variable or
ball-valve obstruction, inspiratory and expiratory anteroposterior chest x-ray films will
show a relative shift of the mediastinum to the unaffected side during expiration. With
time, the affected side will display hyperaeration (Fig. 44.3).

FIGURE 44.3. Inspiration(left) and expiration (right)
chest x-rays. Notice the hyperaeration of the right lung
(seen best on the expiration film) as a result of a right
mainstem bronchus foreign body.



Fluoroscopy
Fluoroscopy is a dynamic study useful for confirmation of findings of plain radiography.
The presence of a retropharyngeal mass is seen on a lateral fluoroscopic examination of
the neck. Caution is exercised, because young children may have a pseudomass, the
normal variation in the prevertebral soft tissue associated with respiration. The ball-valve
effects of a bronchial foreign body can be similarly demonstrated. Other dynamic airway
lesions, such as laryngomalacia, can be revealed with fluoroscopy. Fluoroscopy and
polysomnography have been used together in a technique known as somnofluoroscopy to
demonstrate airway occlusion and its physiologic significance during sleep. Motion
defects of each hemidiaphragm are also revealed by fluoroscopy.
Contrast Radiography
Before the advent of magnetic resonance imaging (MRI) and computed tomography
(CT), barium swallow was often used to assess children with airway compromise, to help
rule out a vascular ring, or to help localize an extrinsic compressive mass. Although still
occasionally used as an inexpensive imaging technique, MRI and CT have nearly
replaced barium swallow for these purposes. Barium swallow is useful for demonstrating
gastroesophageal reflux, aspiration, and tracheoesophageal fistula. Newer techniques
with the modified barium swallow may demonstrate pathologic deglutition that would
otherwise be difficult to diagnose.
Polytomography
Polytomography is included for historical purposes. It has been useful for the evaluation
of intrinsic laryngeal and tracheal lesions. Because polytomes can be obtained in sagittal
and coronal planes, polytomography historically has been superior to CT, which is
restricted to axial planes. However, the development of spiral computed data acquisition
techniques has all but replaced polytomography for the evaluation of the airway.
Ultrasonography
The use of ultrasonography is limited in the evaluation of the airway because of the
sonographic barrier that air produces. It is most useful in the evaluation of the solid or
cystic nature of extrinsic cervical airway masses. These include thyroid masses,
thyroglossal duct cysts, branchial apparatus abnormalities, hemangioma, and
lymphangioma. Laryngoceles are intrinsic airway masses that may extend to more lateral
cervical regions and may be evaluated effectively by ultrasound. Ultrasonography has
successfully detected cervical masses that may cause airway obstruction in the fetus,
allowing preparation for airway intervention at parturition.
In recent years, new high-frequency ultrasound equipment has been developed that has
improved the use and the resolution of endoluminal ultrasound. This technique provides
useful supplemental information that allows more accurate assessment of the size and
degree of infiltration of laryngeal neoplasms (4).
Arteriography
The use of arteriography in the evaluation of the airway is limited to the study of
anomalies of the great vessels and vascular masses. Vascular masses that may jeopardize
the airway include juvenile nasopharyngeal angiofibromas and glomus tumors.
Arteriography with or without embolization is used to evaluate these lesions. CT with
intravenous contrast and MRI are used with increasing frequency as noninvasive
alternatives to arteriography.
Computed Tomography
Over the past two decades, CT has become an invaluable aid in the evaluation of head
and neck lesions. Advances in technology have allowed for high-resolution CT to
delineate even the most intricate structures in the head and neck. CT can provide cross-
sectional images in the axial plane for neck scanning and in the axial and coronal planes
for head and face scanning. Spatial delineation is excellent, and bony definition is
superior to all other imaging modalities.
CT has become the imaging modality of choice in trauma of the facial skeleton and
larynx and in bony abnormalities of the head and neck, such as choanal atresia or
stenosis, and bone-eroding lesions of the nose and nasopharynx (Fig. 44.4). CT is also
helpful to delineate the extent and differentiation of extrinsic and intrinsic airway masses.
CT with contrast may aid in the diagnosis of vascular lesions and deep neck abscesses.

FIGURE 44.4. Computed tomographies of the larynx. A:
At level of vallecula. E, epiglottis. B: At level of glottis.
C, top of cricoid cartilage; P, piriform sinus; T, thyroid
cartilage. C: At subglottic level. I, inferior cornu of
thyroid cartilage; C, cricoid cartilage.



Disadvantages of CT include its greater cost, higher radiation exposure, and limitation to
axial scans for the larynx and trachea. CT provides a static image. Ultrafast or cine CT
provides a dynamic evaluation of the airway and produces up to 17 axial scans per
second. This technique has been used to define the site of narrowing in a dynamic airway
lesion, as in obstructive sleep apnea. Recent work has described the use of helical (spiral)
CT (5). Ultrafine three-dimensional images are possible, as data are collected during a
continuous helical x-ray exposure. Overlapping volumetric data are reconstructed,
providing finely detailed views of the extrinsic and intrinsic airway (6).
In a recent comparative study of laryngeal cancer staging by laryngoscopy versus CT, the
staging accuracy was 51% for laryngoscopy alone and 70% for CT alone. When staging
was based on both modalities, staging accuracy was 80%. Laryngoscopy alone tended to
understage larger tumors (T3 and T4) and CT underestimated smaller tumors (T1 and
T2), leading to the recommendation that both modalities should be used (7).
Magnetic Resonance Imaging
MRI enjoys some of the same advantages as CT for evaluation of the upper airway, such
as cross-sectional images and excellent spatial resolution (Fig. 44.5). However, MRI does
not rely on ionizing radiation and can demonstrate the anatomic site in question in
multiple planes. This is very useful for tracheal and laryngeal airway imaging, which is
best performed in the coronal or sagittal planes. Bone is not seen on MR images; thus CT
is superior for imaging bony structures.

FIGURE 44.5. Magnetic resonance imaging, lateral view
of upper airway. Patient has a tracheotomy for subglottic
stenosis. S, stenosis; T, tracheotomy site.



MRI is rapidly becoming the imaging procedure of choice for many head and neck
lesions. It offers excellent tissue differentiation of mass lesions. MRI is useful to evaluate
and define the extent of nasal encephaloceles, gliomas, head and neck malignancies,
parapharyngeal space lesions, and other extrinsic and intrinsic lesions of the airway.
Vascular pathology lends itself to MRI because of the natural difference in signal
intensity of the surrounding tissues and blood moving through vessels. MR angiography
serves an adjunctive role in the evaluation of vascular lesions in the head and neck.
ENDOSCOPIC ASSESSMENT
Diagnostic Endoscopy
Endoscopy of the upper airway has improved in recent years as a result of technologic
advances in optical imaging systems. Sophisticated technology now offers excellent
visualization of the airways with both rigid and flexible endoscopic equipment. Flexible
systems offer greater diagnostic capabilities because they can be used to visualize
subsegmental bronchi and the upper lobe bronchi, which are beyond the reach of rigid
scopes. In general, flexible scopes can be used under topical anesthesia with greater
patient comfort than their rigid counterparts. They also provide a more physiologic
examination because they do not interfere with function. However, rigid endoscopes are
far superior in their use for biopsies, obtaining cultures, retrieval of foreign bodies, and
surgical intervention. The head and neck surgeon should be experienced in the use of
both rigid and flexible endoscopes for the evaluation and treatment of upper airway
disorders (8).
Upper airway endoscopy may be used for both diagnostic and therapeutic purposes, but
for the purposes of this chapter we stress diagnostic endoscopy. Typically, diagnostic
endoscopy is performed for one of the following reasons: airway obstruction, stridor,
laryngeal mass, atypical asthma, tracheotomy decannulation, persistent cough,
hemoptysis, hoarseness, abnormal chest x-ray film, persistent atelectasis, foreign body,
recurrent respiratory symptoms, neck mass, or the workup of head and neck neoplasms.
Contraindications to upper airway endoscopy are few. Cervical spine disorders that
preclude adequate extension and flexion of the head and neck would be relative
contraindications to the use of rigid endoscopy but would not interfere with flexible
endoscopy. Obviously, coagulopathy is a relative contraindication to any sort of
instrumentation. Seriously debilitated patients may not be candidates for endoscopy for a
variety of medical reasons. Patients who have significant airway compromise should not
undergo flexible endoscopy unless rigid equipment is readily available to establish an
airway if the patient's airway deteriorates.
Flexible Laryngoscopy and Bronchoscopy
Flexible endoscopy may be performed under general or topical anesthesia. Topical
anesthesia can be achieved successfully with tetracaine, cocaine, or lidocaine applied by
atomizer to the oral cavity, pharynx, and base of tongue. If the endoscope is to be
introduced through the nose, then anesthetic and decongestant agents may be applied by
placement of cotton or gauze pledgets. Curved laryngeal forceps with gauze soaked with
the anesthetic agent placed in the pyriform sinuses and a curved cannula can be used for
application to the larynx. If cocaine is the topical anesthetic agent, care should be taken
not to exceed 2 mg total dosage. Topical anesthesia can be supplemented by a
percutaneous superior laryngeal nerve block and intravenous sedation. The
glossopharyngeal nerve is blocked by injecting lidocaine laterally at the junction of the
base of the tongue and the posterior tonsillar pillar.
After adequate sedation and anesthesia have been obtained, the flexible scope is
introduced through the nose or mouth. If introduced through the mouth, a bite block is
placed to protect the endoscope from damage. Flexible bronchoscopy can also be
performed under general anesthesia, and the instrument can be advanced through an
endotracheal tube or tracheostomy; unfortunately, this precludes examination of the
laryngeal inlet. Scope movement is usually controlled by a lever for motion along one
axis and by rotation of the scope for movement into other axes. Many flexible
bronchoscopes also provide ports for irrigation and suction and an instrument port;
washings, cultures, and biopsies may be obtained through these ports. Fluoroscopy can be
combined with endoscopy to direct biopsies of peripheral lung lesions.
Large flexible bronchoscopes are limited to use in nonpediatric patients, because
ventilation occurs around the scope, thus limiting ventilation in smaller airways.
However, appropriate size scopes are available for all but the smallest of children. Some
of the newer instruments may include a ventilation port to circumvent this problem.
However, if there is a concern regarding the patient's airway, rigid endoscopy allows
ventilation during the examination. Flexible bronchoscopes have been used very
effectively to direct the endotracheal tube in the patient who is difficult to intubate. In this
technique, the bronchoscope is placed through the endotracheal tube before insertion into
the patient's mouth or nose. After the flexible scope is introduced through the glottis
under direct visualization, the endotracheal tube is advanced, using the scope as a stylet.
This technique may be used to secure the airway in any patient undergoing flexible
bronchoscopy.
Rigid Laryngoscopy and Bronchoscopy
Local anesthesia may be used, but for patient comfort we usually perform rigid
endoscopy under general anesthesia. In every endoscopic procedure, planning of airway
management must be coordinated with the anesthesiologist. A team approach with good
communication preoperatively averts many obstacles and provides the best patient care.
Rigid bronchoscopes of varying sizes and other instruments, including a variety of
foreign body forceps and suction catheters, should be assembled and ready to use before
anesthetic induction of any patient with a marginal airway. A tracheotomy set should also
be available.
Many laryngoscopes are available (Fig. 44.6). The head and neck surgeon should be
familiar with the intubating laryngoscope (and all of its blades), the Jackson
laryngoscope, the anterior commissure laryngoscope, operating laryngoscopes, and the
subglottiscope. Laryngoscopy in the neonate is performed without anesthesia using the
laryngoscope with the tip placed in the vallecula and the 30-degree rigid telescope
inserted into the laryngeal introitus. This provides a clear view of the larynx without
interfering with vocal cord movement. The Jackson laryngoscope may be used as an aid
in intubation. Once the vocal cords are visualized, the endotracheal tube or bronchoscope
is passed through the Jackson scope, which has a removable piece that allows removal of
the laryngoscope after intubation of the airway. The anterior commissure scope offers
excellent visualization of the anterior commissure, and biopsies can be performed with
ease. However, laser surgery is performed through an operating laryngoscope such as the
Jako or Dedo. Surgery of the subglottic area is best performed using the subglottiscope.
Some laryngoscopes have side ports that allow jet ventilation and suction, which offer
distinct advantages when using lasers. Most standard laryngoscopes also have the
capacity for suspension, allowing hands-free laryngoscopy mandatory for microscopic
or laser procedures.

FIGURE 44.6. Various laryngoscopes. A: Jackson. B:
Holinger anterior commissure. C: Jako. D: Dedo. E:
Holinger slotted laryngoscope, used for ease of
instrument manipulation such as injecting Teflon.



Contemporary rigid bronchoscopes are available in multiple sizes and incorporate a rigid
telescope with distal illumination (Fig. 44.7). Additional ports are available for
ventilation, instrumentation, and suctioning. Telescopes have also been adapted to
forceps, ensuring precise retrieval of foreign bodies or biopsy specimens. Camera and
video systems are also used to aid in instruction of training surgeons. The safety of
telescopic endoscopy is well documented.

FIGURE 44.7. Karl Storz bronchoscope. A, ventilation
port; B, instrument port; C, attachment site for distal
illumination.



Head and neck position is crucial during rigid endoscopy. Typically, the neck is flexed
forward on the chest, and the head is extended on the neck in the sniff position. A
doughnut headrest may aid in correct positioning of the patient by elevating the head 10
to 15 cm above the table. Having an assistant support the head can aid in maintaining the
proper position. Once the patient is in position, a guard is placed to protect the teeth and
gums. The laryngoscope is introduced on the side of the mouth in an attempt to sweep the
tongue to the opposite side of the oral cavity. The scope rests on the left thumb and
forefinger like a pool cue, which helps protect the teeth and gums. The scope is advanced
slowly, using the right hand to stabilize it. The laryngoscope is used to examine all parts
of the supraglottis, glottis, and hypopharynx.
The bronchoscope is introduced in a manner similar to the laryngoscope, but when the
vocal cords are visualized, it is turned so that the leading edge is directed in the anterior-
posterior direction before entry. This allows a nontraumatic passage between the vocal
folds. The trachea and bronchi are then completely examined in an orderly sequence. If
there is a question of tracheomalacia or bronchomalacia, the patient should be allowed to
ventilate spontaneously (if under general anesthesia). The trachea may be compressed by
either an extrinsic mass or an abnormally placed vascular structure. Perhaps the most
common offending vessel is a premature takeoff of the innominate artery, which
produces a characteristic 11 to 4 o'clock slanting compression of the anterior wall of the
trachea. This can be confirmed by passing the tip of the bronchoscope past the
indentation and then lifting the bronchoscope anteriorly, compressing the innominate
artery. An assistant palpating the pulse in the right arm should notice a reduction of loss
of the pulse.
Varying the angle of the telescope (0, 30, 75, and 90 degrees) enhances visualization of
segmental bronchi. Any suspicious lesions may be cultured or biopsied, but the
endoscopic examination should be completed before biopsy. This will prevent any
confusion as to the pathology and provide a blood-free field for better visualization.
COMPLICATIONS
Complications are unusual in endoscopy. Nonetheless, the inexperienced endoscopist can
turn what is usually an uncomplicated procedure into a potentially fatal one. Perhaps the
most common complication is damage to the teeth, particularly the upper incisors.
Carefully padding the teeth and supporting the bronchoscope with the thumb will avoid
this problem. Perforation can be a deadly complication. The endoscopist can avoid
perforation by maintaining a view of the lumen. If it occurs, corrective steps should be
taken immediately. These may include primary repair and chest tube drainage as
appropriate. Pneumothorax can result from perforation by the bronchoscope or a vigorous
biopsy. Another cause of pneumothorax is jet ventilation at high pressures or if the
patient is not permitted to exhale completely before insufflating again. This may occur
when ventilating past obstructing lesions such as carcinoma or papilloma.
Laryngospasm can occur during any manipulation of the airway. Some endoscopists
believe that applying a topical anesthetic to the vocal folds at the end of the procedure
may reduce the incidence of laryngospasm. If laryngospasm occurs, positive pressure by
mask will usually correct the problem. However, if the laryngospasm persists and the
patient attempts to inspire vigorously against the closed glottis, negative pressure
pulmonary edema may result. Rapidly decreasing oxygen saturation, elevated airway
pressures, and pink-tinged frothy sputum suggest the diagnosis. Chest x-ray film is
confirmatory. Proper management includes oxygen supplementation, positive end-
expiratory pressure, and possibly diuretic therapy.
THE FUTURE
The optics of flexible endoscopic equipment continue to improve, although they remain
inferior to those of the rigid equipment. Laryngoscopes that incorporate a small telescope
and television camera have been developed that provide excellent visualization of the
larynx and photodocumentation. Modifications are being made in both rigid and flexible
bronchoscopes that continue to make the use of lasers easier.

HIGHLIGHTS
Information from the history will often permit the physician to
make a diagnosis or at least narrow the differential diagnosis
significantly.
Modern endoscopic equipment permits the endoscopist to
evaluate virtually all areas of the supraglottic airway in the
office.
Pulmonary function tests may localize the lesion and offer a
means of determining the effectiveness of therapy.
In many cases, a high-voltage soft-tissue lateral x-ray film of
the neck is the only radiographic evaluation necessary.
However, CT and MRI now provide the physician with images
of the airway in a variety of orientations.
Both rigid and flexible endoscopy can be performed under local
anesthesia. Flexible endoscopy is better tolerated under local
anesthesia and permits examination of the distal
tracheobronchial tree. Rigid endoscopy has the advantage of
controlling the airway and is the only safe technique for foreign
body removal. Both types of endoscopy have low complication
rates.
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2. Sataloff RT. Office evaluation of dysphonia. Otolaryngol Clin North Am 1992;25:843855.
3. Yin SS, Oiu WW, Stucker FJ, et al. Value of electromyography in differential diagnosis of
laryngeal joint injuries after intubation. Ann Otol Rhinol Laryngol 1996;105:446451.
4. Arens C, Glanz H. Endoscopic high-frequency ultrasound of the larynx. Eur Arch
Otorhinolaryngol 1999;256:316322.
5. Zelberg AS, Silverman PM, Sessions RB, et al. Helical (spiral) CT of the upper airway with three-
dimensional imaging: technique and clinical assessment. AJR Am J Roentgenol 1996;166:293
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6. Silverman PM, Zeiberg AS, Troost TR, et al. Three-dimensional imaging of the hypopharynx and
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7. Ferri T, De Thomasis G, Quaranta N, et al. The value of CT scans in improving laryngoscopy in
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

45 TASTE
Head & Neck SurgeryOtolaryngology
45




TASTE
JOHN F. KVETON
LINDA M. BARTOSHUK

J.F. Kveton and L.H. Bartoshuk: Department of Surgery, Section of Otolaryngology, Yale University
School of Medicine, New Haven, Connecticut.


Distinctions Between Taste and Olfaction
Qualities
Mixtures: Analytic or Synthetic?
Flavor
Anatomy of the Taste System
Tongue
Peripheral Nerves
Central Connections
Interactions Within the Nervous System
Genetic Variation in Taste
Evaluation of the Taste Sense
Taste Loss or Intensification
Thresholds
Taste Phantoms or Dysgeusia
Dysgeusia Resulting from a Genuine Stimulus
Taste Phantoms
Taste Loss or Alteration Produced at Vulnerable Loci in the Taste System
Tongue
Venous Taste
Peripheral Nerves
Nervus Intermedius
Glossopharyngeal Nerve
Central Nervous System
Cumulative Taste Loss
Phantoms From Damage to Peripheral Structures
Peripheral Nerves
Epilepsy
Capsaicin: A Novel Way to Treat Oral Pain
Effects of Age on the Sense of Taste
Effects of Cancer and Cancer Therapies on the Sense of Taste
Effects of Medications on the Sense of Taste
Taste Changes With Disease
Coping With Taste Disorders
Acknowledgments
Chapter References
There are two kinds of taste disorders: losses (hypogeusia refers to a partial loss that can
be differential with regard to quality or location and ageusia refers to a total loss) and
chronic taste sensations that occur in the absence of obvious stimulation (dysgeusia).
Some dysgeusias arise within the nervous system and are akin to phantoms in other
sensory systems (e.g., phantom limb, tinnitus); we call these taste phantoms. Others
reflect the presence of some abnormal substance in the mouth that is perceived by a
completely normal taste system.
In the sections that follow, we distinguish between taste and smell (a distinction often not
made correctly by the patient) and describe the anatomy and physiology of the taste
system, including interactions within the nervous system and the consequences for
clinical problems. We then discuss the principles important to a clinical evaluation of the
sense of taste, including ways to distinguish between true taste phantoms and the
perception of abnormal stimuli in the mouth. Finally, we relate taste disorders to the
vulnerable points in the taste system, and we consider the effects of genetic variation,
aging, medications, and disease on taste.
DISTINCTIONS BETWEEN TASTE AND OLFACTION
Qualities
Taste and olfaction are often confused in the minds of patients because taste is used as a
synonym for flavor in ordinary conversation. Taste refers to sensations arising from the
taste buds embedded in the tissues of the tongue, palate, and throat. The taste sensations
are generally believed to be salty, sweet, sour, and bitter. Olfactory qualities are much
more numerous than those of taste, but just how much more numerous remains open to
argument. The claim is commonly made that humans can recognize more than 10,000
odors (1). Unfortunately, there is no empiric evidence on this point. Engen (2) noted that
such claims seem to be referring to the ability to discriminate between odorants presented
simultaneously rather than to the ability to recognize and identify odorants presented one
at a time. The ability to recognize and identify a particular odorant obviously depends on
experience with the odorant. However, even considerable experience does not guarantee
successful identification. Cognitive factors play important roles in odor identification. For
example, patients may be unable to name an odorant initially when tested, but if told the
correct name, they will be able to correctly name it on a later presentation. Cain et al. (3)
developed a very successful clinical olfactory test based on providing this feedback to
ensure optimal performance.
Mixtures: Analytic or Synthetic?
The way in which mixtures are perceived is a very important attribute of any sensory
modality. In a synthetic mixture, the qualities of the components cannot be recognized in
the mixture. For example, when red and green lights are mixed (as on a color wheel), the
result is yellow, which is a new quality. On the other hand, in an analytic mixture, the
qualities of the components are recognizable. For example, when you play a high note
and a low note on the piano, both can be recognized, and there is no new tone.
Most investigators consider taste mixtures to be analytic. The analytic nature of taste
permits us to identify substances with important nutritional consequences when they are
present in complex mixtures. For example, we can recognize sodium chloride, sucrose,
and bitter poisons mixed in foods when their sensations must be differentiated from those
produced by many other substances. On the other hand, olfaction may show both kinds of
mixing. There are many examples of analytic mixing in ordinary experience (e.g., one
can smell the flowers on a dinner table and the roast turkey without confusion), but there
are also cases where a mixture does not smell like its components. Cain (4,5) suggested
that we usually code olfactory mixtures holistically but that we have the ability to learn to
analyze them as well. For example, we can recognize pizza as a unitary smell, but we can
also recognize at least some of the component smells in it. The ability to process odor
mixtures holistically allows us to recognize a food by its characteristic odor. That odor
can then be associated with the effects of nutrients. For example, starch and fat, both
important sources of calories, do not have tastes or odors to humans (although they do
produce characteristic touch sensations in the mouth). We learn to associate the effects of
the calories with the sensory characteristics (especially the smell) of the food that
contains them (6).
Flavor
Flavor is the combination of taste and smell. When substances are sniffed, odorants pass
though the nostrils and rise in the nasal cavity (orthonasal olfaction). When food is
chewed and swallowed, tastants contact the taste buds on the tongue, throat, and palate
while odorants are pumped behind the palate into the nasal cavity (retronasal olfaction).
By either route, odorants eventually reach the olfactory cleft at the top of the nasal cavity.
If the cleft is blocked (e.g., with polyps) or the olfactory neurons are damaged (e.g., by
head trauma or viral invasion), then the olfactory component of flavor will be absent.
Because taste and flavor are synonyms in common speech, patients who cannot smell
may say that they cannot taste as well. A few simple questions can clarify the taste-smell
distinction for the patient. Ask if the patient can taste salt crystals, sugar crystals, the sour
taste of vinegar or lemon juice, or the bitter taste of dark chocolate or coffee. The typical
patient says, in effect, yes I can taste those, but I cannot taste anything else. There is
nothing else as far as taste is concerned. Such a patient is experiencing an olfactory loss,
not a true taste loss.
ANATOMY OF THE TASTE SYSTEM
Tongue
Taste Buds
The taste bud is a globular cluster of cells arranged something like the segments of an
orange. The tips of some of the cells taper to thin extensions of the cell membrane,
microvilli, that project above the taste bud into an area called the taste pore. The taste
pore is sealed with a dense substance that prevents tastants from contacting any other
parts of the cells.
The cells in the taste bud are not all alike. Some appear darker than others by electron
microscopy, leading to a dark-light distinction, but morphologic characteristics have also
been used to differentiate the cells. At an earlier time, it was uncertain whether there were
various cell types or whether there was one cell type with various developmental stages,
but current opinion favors distinct cell types (7). Taste receptor cells have a limited
lifespan measured in days. They are continually replaced from basal cells. This suggests a
point in the system that is vulnerable to nutritional state, to drugs that might interact with
cell turnover, and to radiation (8).
Receptor Sites and Taste Stimuli
The membrane on the microvilli that project into the taste pore contains the sites at which
stimuli first interact with the taste system. Salts and acids (ionic stimuli) interact with ion
channels in the membrane; sweet and bitter substances (usually organic compounds)
interact with receptors in the membrane (9). For many years, the source of saltiness was
believed to be the cation of a salt. In fact, some species have neurons in their taste
systems that are sodium specialists. However, recent work suggests the possibility that in
humans the salty taste is produced by the chloride anion (10). This is very important
theoretically and practically (e.g., the development of sodium substitutes).
Through the years, there have been many attempts to find the structure(s) responsible for
sweetness. These were generally unsuccessful until Shallenberger and Acree (11) noted
that most sweeteners provided two sites that could hydrogen bind to the receptor
membrane. Later a third site was added. Psychophysical work suggests more than one
type of receptor mechanism for sweetness. For example, relatives of diabetics show a
disorder for the taste of glucose but not for fructose (12).
For bitterness, the evidence is even more clear that there is more than one kind of
receptor mechanism. For example, the tongue can be adapted to one bitter substance and
remain completely unadapted to others.
Taste Quality Coding
Early neurophysiologic studies failed to find taste neurons specific to the four basic
tastes, and this led to the theory that taste quality was coded by the pattern of activity
generated by a stimulus across a population of taste neurons. However, later work with
more species and larger numbers of neurons suggested that there were, in fact, fiber types
specific to each of the four basic tastes (see the work of Frank [13]) and that these types
act as labeled lines for the four basic tastes.
Taste Papillae
The tongue gets its bumpy appearance from four types of papillae. The most numerous of
these, filiform papillae, have no role in taste. However, in species like the cat, filiform
papillae are shaped like the rasps on a file and assist in licking. The fungiform papillae
are visible as small red structures and are most densely distributed on the tip and the
edges of the anterior two thirds of the tongue. The density diminishes toward the center
of the tongue, leaving this area virtually devoid of fungiform papillae in many
individuals. The fungiform papillae are easy to see on the human tongue using a
procedure developed by Miller and Reedy (14). The tongue is stained with blue food
coloring. The fungiform papillae do not stain well and so can be seen as pink circles
against the blue background. High magnification reveals blue spots (from 0 to about 15)
on the fungiform papillae; the blue spots are taste pores, the conduits to the taste buds.
Incidentally, in early experiments, the tongue was stained with methylene blue. However,
there have been suggestions (15) that methylene blue plus light may cause DNA to
mutate. Although there is no reason to conclude that methylene blue is dangerous when
used with videomicroscopy, we note that food colorings can also be used for the same
purpose.
The foliate papillae are located between adjacent folds on the edges of the base of the
tongue. They are easy to visualize with the mouth wide open and the tongue pulled to one
side. The foliate papillae are a deeper red than the surrounding tissue because the mucosa
is thinner. Anterior to the foliate papillae, there are ridges and furrows that can be seen as
a series of parallel lines on the edges of the tongue; these are the lateral rugae. They
contain some fungiform papillae.
The circumvallate papillae are raised circular structures on the rear of the tongue. The
largest circumvallate papilla is usually in the middle, with three or four smaller papillae
on either side forming an inverted V.
Tongue Map
One of the myths in the taste field that has been very resistant to correction is that of the
tongue map. Many texts show a picture of the tongue showing that sweet is perceived on
the tip of the tongue, sour along the edges, bitter in the back, and salty about equally on
all locations. The historical accident that led to this map was first discovered by Collings
(16). The map has its origins in the thesis of Honig done in the laboratory of Wilhelm
Wundt in Leipzig in 1901. Honig measured thresholds for the four basic tastes on various
loci. He did find differences. Thresholds for sweet were the lowest on the front of the
tongue, whereas those for bitter were the lowest on the back of the tongue, and so on.
However, the differences were very small. When his work was summarized in English,
the thresholds were converted to sensitivity by taking the reciprocals. The lower
threshold for sweet on the tip thus became a higher sensitivity score. The size of the
differences was completely lost, leading later readers to infer that sweetness not only was
the greatest for the tip of the tongue but also was absent on other loci. In fact, as any
observer with cotton-tipped swabs and a few taste stimuli can ascertain, the four taste
qualities can be perceived on all loci where there are taste buds (17).
Peripheral Nerves
Taste is mediated by three cranial nerves: VII, IX, and X. The two most important nerves
are the glossopharyngeal (IX) and the facial nerve (VII). The components of the facial
nerve include the chorda tympani and the greater superficial petrosal nerve, which arise
from the smaller afferent portion of the facial nerve known as the nervus intermedius.
The glossopharyngeal nerve (IX) provides complex motor and sensory innervation to the
pharynx and base of the tongue. Taste sensations from the circumvallate papillae at the
junction of the posterior third and anterior two thirds of the tongue and the foliate
papillae at the rear edge of the tongue are mediated by the lingual branches of cranial
nerve IX. These nerves also provide the general afferent neurons to the mucous
membrane of the base of the tongue. These branches course along the margin of the
styloglossus muscle, running deep in the tonsillar bed. In this region, the tonsillar
branches are incorporated into the nerve deep to the hyoglossus muscle. The nerve then
continues cephalad over the lateral aspect of the stylopharyngeus muscle and continues
along its posterior border. The stylopharyngeus is the only muscle that derives motor
innervation from cranial nerve IX. The nerve continues medial to the external carotid
artery and anteromedial to the internal carotid artery where the afferent cell bodies are
contained in the inferior petrosal ganglion. This ganglion is just anterior to the superior
cervical sympathetic ganglion and communicates with it and the superior ganglion of the
vagus nerve. The glossopharyngeal nerve then courses along a groove on the inferior
aspect of the petrous bone and enters the jugular foramen. The smaller superior petrosal
ganglion, also containing unipolar cell bodies, is usually found within the jugular canal.
The glossopharyngeal nerve lies anteriorly in the jugular foramen, bordering the orifice
of the inferior petrosal sinus. The nerve then exits the foramen most anteriorly, running
10 to 20 mm through the cerebellopontine angle to enter the retroolivary area of the
medulla. Fibers proceed into the upper portion of the fasciculus solitarius, terminating in
the nucleus solitarius (the gustatory nucleus).
The chorda tympani receives taste information from the fungiform papillae on the
anterior two thirds of the tongue and may also receive information from the foliate
papillae as well. The chorda tympani runs along with the lingual nerve, which provides
sensation to the same region of the tongue. These nerves leave the undersurface of the
tongue, turn downward medial to the duct of the submandibular gland, and then ascend
across the duct lateral to the surface of the hyoglossus and styloglossus muscles. The
chorda tympani also supplies preganglionic parasympathetic fibers to the submandibular
ganglion, which is located on the hyoglossus muscle near the posterior border of the
mylohyoid muscle. This ganglion supplies parasympathetic innervation to the
submandibular and sublingual glands. The nerves then cross the mandibular attachment
of the superior constrictor muscle and enter the infratemporal fossa between the medial
pterygoid muscle and the mandible. High in the infratemporal fossa, the chorda tympani
nerve leaves the lingual nerve and crosses the medial surface of the spine of the sphenoid.
It proceeds into the petrous portion of the temporal bone through the petrotympanic
fissure (Huguier canal). The chorda tympani exits into the superolateral aspect of the
middle ear. The nerve is then suspended in the middle ear space, running medial to the
neck of the malleus and lateral to the long process of the incus before entering a bony
canaliculus in the posterior tympanum just medial to the fibrous annulus. The chorda
tympani traverses this canal, which runs medially until it joins the fallo-pian canal in the
mastoid. This juncture usually occurs about 5 mm proximal to the stylomastoid foramen.
The chorda tympani then travels within the facial nerve throughout the mastoid and
horizontal segment of the facial nerve to the geniculate ganglion. The afferent and
visceral efferent fibers leaving the geniculate ganglion with the facial nerve are known as
the nervus intermedius (Wrisberg nerve). This nerve exits the labyrinthine segment of the
facial nerve separate from the motor division of the facial nerve. Once in the internal
auditory canal, the nervus intermedius separates into a thin nerve of one to several fiber
bundles and exits into the cerebellopontine angle between the facial nerve and the
vestibulocochlear nerve. Its course in the posterior fossa is often closer to the eighth
nerve than the seventh until it enters the pons between the fibers of the motor root of
cranial nerve VII and the vestibular root of cranial nerve VIII. These fibers enter the
solitary fasciculus, terminating in the upper portion of the nucleus solitarius.
The greater superficial petrosal nerve contributes to taste through its innervation of the
palate. The palatal taste buds are located on the margin between the hard and soft palates.
The palatal fibers course indistinguishably with the lesser palatine nerve (V2), enter the
lesser palatine foramina, and ascend as the greater palatine canal into the pterygopalatine
fossa. At the pterygopalatine ganglion, these fibers synapse and join with the deep
petrosal nerve to traverse the pterygoid canal as the nerve of the pterygoid canal. As it
exits the pterygoid canal, the fibers become the greater superficial petrosal nerve, which
crosses the foramen lacerum lateral to the internal carotid artery. The nerve proceeds
deep to the semilunar ganglion, traversing the petrous portion of the temporal bone
extradurally until it exits the middle cranial fossa at the facial hiatus to join the anterior
margin of the geniculate ganglion. From the geniculate ganglion, fibers run with the
nervus intermedius in a similar fashion to those of the chorda tympani.
The superior laryngeal nerve, a branch of the vagus (tenth) cranial nerve, innervates taste
buds on the laryngeal surface of the epiglottis. Its role in everyday taste perception is
unknown.
Central Connections
Taste fibers from cranial nerves VII, IX, and X compose part of the solitary fasciculus
and terminate on second-order gustatory neurons in the rostral half of the nucleus
solitarius in the medulla. The taste projections from the medulla terminate in the most
medial small-celled division of the thalamic ventroposteromedial nucleus adjacent to
neurons that respond to somatosensory stimulation of the tongue and oral cavity. Recent
anatomic and electrophysiologic studies in primates and clinical studies in humans
support an ipsilateral gustatory system that ascends to the thalamus via the central
tegmental tract (18).
On cortex, the weight of the current evidence is that the central gustatory system in
humans is largely ipsilateral and nonlemniscal with the primary cortical representation
straddling the circular sulcus that separates the frontal operculum from the insula (18)
(Fig. 45.1).

FIGURE 45.1. Peripheral and central nervous system
structures for taste.



Interactions Within the Nervous System
Interactions Among Taste Nerves
One of the most remarkable clinical observations that can be made about taste is how rare
taste loss seems to be. Even when the taste system is known to have been damaged, there
are few complaints of taste loss. Nature has provided some compensation mechanisms
that make taste very robust, and these depend on the fact that taste nerves inhibit one
another (19). The release of inhibition phenomenon helps explain why patients fail to
notice changes in everyday taste experience even when they are known to have had
significant damage to the taste system. However, why do patients not notice the change in
the location of taste sensations in their mouths? The answer is that taste is poorly
localized even in a normal mouth. For example, the taste papillae on the tongue
essentially form an oval on the tongue with the fungiform papillae on the front and
anterior edges, the foliate papillae on the posterior edges, and the circumvallate papillae,
completing the oval, across the rear of the tongue. In addition, the palatal taste buds are
sensations as originating from these loci. Rather, taste sensations seem to come from the
whole mouth. We believe that the localization of taste sensations is actually mediated by
the sense of touch (20,21), as is known to be the case with thermal sensations. Thermal
stimulation of different areas of the tongue have been demonstrated to elicit specific
tastes.
GENETIC VARIATION IN TASTE
Genetic variation to taste has been noted since the 1930s and has had a considerable
impact on everyday oral perception and nutritional health (22,23,24 and 25). Three
phenotypic groups have been identified based on their ability to perceive bitterness in 6-
n-propylthiouracil (PROP). Nontasters perceive no bitterness to PROP, whereas medium
tasters perceive saturated PROP to be moderately bitter, and supertasters perceive it to be
extremely bitter. Supertasters may carry two dominant alleles (TT) and medium tasters,
one dominant and one recessive allele, but this has yet to be proved. Women are more
likely to be supertasters than men, and supertasters are more common in certain races
(e.g., Asian vs. white).
Anatomically, supertasters have larger numbers of fungiform papillae than nontasters.
Supertasters perceive more intense taste sensations for most of the taste substances tested
so far. Taste buds in fungiform papillae are innervated by two cranial nerves, VII and V.
Neurons from cranial nerve VII synapse with taste receptor cells, whereas those from
cranial nerve V do not contact receptor cells but rather form a basket of nerve endings
around the taste buds. Because supertasters of PROP have many more taste buds than
nontasters, it is not surprising that they perceive more intense oral burn from irritants like
chili pepper, black pepper, and ethanol (22) and they have lower two-point thresholds,
showing greater touch sensitivity (Prutkin, unpublished data). On the back of the tongue,
taste, touch, and thermal sensations are all mediated by cranial nerve IX. Supertasters
perceive greater oral burn on this locus as well (Cunningham, unpublished data).
Incidentally, these data suggest that supertasting is of special interest for women's health;
postmenopausal women who are supertasters experience much greater oral pain from
capsaicin (chili peppers) than nontasters (26). There is evidence that PROP taste is
dependent on hormones throughout a woman's lifespan. We are interested in the
possibility that loss of PROP receptors at menopause may result in release of inhibition in
cranial nerve V, thereby producing greater perceived intensities from oral irritants and, in
some women, pain phantoms (e.g., burning mouth syndrome in postmenopausal women
may be a pain phantom). Supertasters, with their much more abundant pain innervation,
might be expected to be at greatest risk for this (27).
EVALUATION OF THE TASTE SENSE
Taste Loss or Intensification
An evaluation for taste alteration (we note that losses are much more common than
intensifications) should assess the attributes of taste that can change with damage.
Damage can affect taste quality or intensity and can also affect localized parts of the taste
system (e.g., one nerve can be damaged and the others remain intact).
Because the taste qualities can be affected differentially, the assessment should use
stimuli of each of the four qualities: salty, sweet, sour, and bitter. Typical stimuli used are
NaCl, sucrose, citric acid, and quinine hydrochloride or quinine sulfate. These
compounds are available in a variety of purities. Reagent-grade chemicals are chemically
pure but cannot be considered biologically safe and so if tasted should not be ingested.
Commercial kosher salt (which lacks additives) and commercial sugar are pure enough to
use for taste tests. NF (National Formulary) or USP (United States Pharmacopeia) citric
acid and quinine are certified biologically safe for prescription formulation and so are
safe for taste tests.
To assess taste intensities in patients, we can use patients as their own control and look
for discrepancies between the right and left sides of the mouth. However, alterations may
not fall into such a convenient pattern. Thus, a clinical evaluation must compare the taste
intensities experienced by patients with those of normal individuals. Unfortunately, this is
the hardest problem to solve in sensory measurement.
Thresholds
The measurement of thresholds seems, at first glance, to offer a simple way to assess
taste. The clinician only needs to determine the lowest concentration of a tastant that can
be discriminated from water. A patient's threshold could then be compared with a
distribution of thresholds from normal control subjects. Unfortunately, using thresholds
to evaluate taste can lead to some serious errors. Figure 45.2 shows the psychophysical
functions for the taste of NaCl obtained in four studies. Panel 1 shows a reduction in
saltiness produced by exposure of the tongue to sodium laurel sulfate, the detergent in
toothpaste (27). Note that the saltiness was reduced proportionately at each concentration.
Panel 2 shows the effects of adaptation to the NaCl in saliva (28). Adaptation to the
sodium in saliva raised the threshold, but the function became very steep just above
threshold so that it caught up to the normal function. Moderate and high concentrations of
NaCl were unaffected by the adaptation. Panel 3 shows the ability of a patient to taste salt
before and 2 months after radiation therapy to the neck (28). After 2 months, the
threshold was normal, but the function did not climb normally as concentration was
raised. The patient was able to detect NaCl but nonetheless lived in a pastel taste world.
Panel 4 shows the average functions for groups of elderly and young subjects (29). For
the elderly subjects, the functions were elevated at the weak concentrations, and the
thresholds were elevated. This suggests that a mild chronic taste (dysgeusia) might have
been present. The addition of that dysgeusia elevated the lower part of the psychophysical
function and made discrimination between water and the dilute concentrations more
difficult, thus raising the threshold.

FIGURE 45.2. Log-log plots of saltiness (in arbitrary
units) versus concentration. Panel 1: Reduction in
saltiness produced by exposure of the tongue to sodium
laurel sulfate, the detergent in toothpaste. The saltiness
was reduced proportionately at each concentration. Panel
2: Effects of adaptation to the NaCl in saliva. This
adaptation raised the threshold, but the function became
very steep just above threshold so that it caught up to the
normal function. Moderate and high concentrations of NaCl were unaffected by the
adaptation. Panel 3: Ability of a patient to taste salt before and 2 months after radiation
therapy to the neck. After 2 months, the threshold was normal, but the function did not
climb normally as concentration was raised. The patient was able to detect NaCl but
nonetheless lived in a pastel taste world. Panel 4: Average functions for groups of elderly
and young subjects.



As Fig. 45.2 shows, changes in threshold often fail to predict changes in suprathreshold
tastes, that is, threshold and suprathreshold perception are dissociated. Because patients
tend to care more about their everyday (i.e., suprathreshold) experience than about their
thresholds, a clinical evaluation must assess suprathreshold experience.
Unfortunately, any attempt to compare suprathreshold taste experiences between patients
and control subjects runs into a classic philosophic problem: We cannot share one
another's experiences. However, the fact that we cannot make absolute comparisons
across people does not prevent us from making relative comparisons. That is, we can
select a standard and ask both the patient and the control subject to compare a stimulus of
interest to that standard. If we are clever enough to select a standard that is perceived the
same by patients and control subjects, we can detect differences in the perception of the
stimulus of interest. Historically, there has been a variety of approaches to the selection
of a standard; the virtues and limitations of these approaches are still a source of lively
debate among psychophysicists (30).
The simplest standard is the use of descriptive adjectives. For example, one can ask
patients and control subjects to assign a number from 0 to 9 to the intensity of tastants
where 0 = no taste, 5 = medium taste, and 9 = very strong taste. This simple method will
detect relatively severe taste losses (31). However, in many cases we have reason to
suspect that intensity adjectives do not reflect the same intensity to all. Concern about
this led Marks et al. (32) to devise a method they call magnitude matching. With this
method, the clinician selects a stimulus from a modality different from the one under
evaluation. For example, when we study genetic variation in taste, we use sound as a
standard. Supertasters of PROP match PROP to loud sounds, and nontasters match it to
soft sounds.
Because adjective-labeled scales are easier for patients and experimenters to use, there is
interest in developing such a scale that can provide valid across-subject comparisons.
Green et al. (33) devised a line with adjective labels spaced so that ratings on the line
have ratio properties (i.e., one rating that is twice as far along the line as another rating
reflects a sensation that is twice as strong). Of special importance, labeling the top of the
scale strongest imaginable sensation of any kind produced results very similar to those
obtained with magnitude matching. That is, both methods appear to act much as universal
sensory rulers that can be used to compare patients with control subjects.
Incidentally, stimuli from more than one modality can be assessed in the same session
with a scale like the modified Green scale. This provides the advantages of a good
adjective-labeled scale with those of magnitude matching (22).
Because taste can be lost on one locus but remain intact on others, taste function should
be determined on various loci. One easy way to do this is with a gustometer. This
technique is based on the fact that a weak electrical stimulus produces a sour taste when
applied to taste receptors. However, the mechanism by which the sour taste is produced is
uncertain. Despite its convenience, this method is inappropriate for the evaluation of taste
qualities other than sour. In addition, great care must be taken to ensure that the metal
stimulator is properly disinfected between patients. More comprehensive spatial taste
tests are done by simply placing taste stimuli on various loci (31,23).
Taste Phantoms or Dysgeusia
The first step in the evaluation of any chronic taste is to ask the patient to describe the
quality of the taste. A chronic taste sensation will be described by a taste quality name,
that is, the patient will state that the taste is bitter, sweet, and so on. Patients often find
chronic olfactory sensations particularly difficult to describe qualitatively and may
simply use a hedonic description, such as unpleasant. Thus, if the patient cannot
describe the sensation, it may actually be an olfactory sensation.
Dysgeusia Resulting from a Genuine Stimulus
If the patient is tasting a real stimulus, then the clinical task is to determine what the
stimulus is, how it is gaining entrance to the mouth, and whether the underlying cause
reflects a medical problem. If the stimulus is a tastant, then it should be possible to rinse
it out of the mouth with water. Even if the taste reappears quickly, the fact that it could be
rinsed away is significant. If an evaluation of the patient's taste system with a spatial test
designed to test each cranial nerve (32) shows no losses, this is further evidence for a
normal taste system perceiving a genuine tastant. Finally, topical anesthesia of the mouth
should abolish a chronic taste due to the presence of a genuine tastant.
Several possible sources for a genuine tastant are saliva (many medications make their
way into saliva), gingival fluid, reflux, postnasal drip, and microorganisms that are
present in the mouth. When the taste is gaining entrance to the mouth via saliva, it can
sometimes be exhausted temporarily by chewing gum (chewing increases the rate of
salivary flow).
The quality associated with the tastant can be a clue as to how that tastant gained entrance
to the mouth. For example, salty or metallic dysgeusia sensations suggest the possibility
that blood is the source of the taste. Blood tastes salty because its NaCl concentration
(approximately 0.15 M) is much higher than that of saliva (approximately 0.015 M
NaCl). A bitter dysgeusia suggests the presence of small amounts of medication in saliva
or gingival fluid.
Taste Phantoms
Taste phantoms are associated with damage to the taste system. Thus, a patient
complaining of a chronic taste should be evaluated to see if any localized areas of the
mouth show taste loss. In some cases, a taste is perceived to arise from an area that is
actually devoid of taste. Obviously, such a taste phantom cannot be due to the presence of
a genuine tastant.
Topical anesthetics can be used to verify that such a taste phantom originates within the
nervous system (34). The patient is asked to rate the intensity of the phantom, and then
the mouth is anesthetized by swishing a topical anesthetic in the mouth for 60 seconds
(e.g., 0.5% dyclonine). We recommend that the patient not gargle with the anesthetic,
because anesthesia of the gag reflex is uncomfortable and unnecessary. After
expectoration of the anesthetic, we ask patients to wait for an additional 60 seconds and
then to rinse thoroughly. We then test with a tastant to ensure that anesthesia is complete
and ask the patient to rate the taste phantom at time intervals (1- to 2-minute intervals are
adequate to reveal changes). If the patient's phantom fails to be abolished or actually
increases, then the dysgeusia obviously must originate from a location central to the taste
receptors. In fact, we typically see intensification of nerve-stimulation phantoms when
the mouth is topically anesthetized. We interpret this as a release-of-inhibition
phenomenon. For example, a salty phantom induced by a mastoidectomy doubled when
the mouth was anesthetized (35). We conclude that the glossopharyngeal nerve (IX)
normally inhibits input from the chorda tympani (VII). Anesthesia of cranial nerve IX
released inhibition on VII, and because the phantom originated from VII, it intensified.
Previously we discussed the phantoms that resulted from anesthesia of the chorda
tympani. These phantoms were localized to a normal area that was not anesthetized.
There may be an analogue to this in patients. Localized damage to the taste system might
produce phantoms that appear to arise from normal areas.
In some cases, patients do not complain of a chronic taste but rather complain that the
taste of certain foods has been altered. If the complaint genuinely involves taste, consider
the possibility that differential losses among qualities may be involved. For example,
some foods and beverages that are sweetened taste unpleasantly bitter when the sweet
taste is removed. Thus, it is not surprising that a patient with a specific loss of the ability
to taste sweet describes these as bitter.
TASTE LOSS OR ALTERATION PRODUCED AT VULNERABLE
LOCI IN THE TASTE SYSTEM
In the following section, we relate vulnerable loci in the taste system to some of the
known pathologies of taste. When the taste system is damaged, the result may be either a
taste alteration (usually a loss) or a taste phantom.
Tongue
Substances that alter taste are thought to do so because they have effects on the taste
membrane. These include foods, beverages, toothpaste, mouthwashes, and medications.
A predominant mechanism is adaptation, when any of a variety of substances remains on
the tongue for an extended time. At this point, if the substance is reapplied it will have no
taste. In other cases, taste changes occur due to direct interaction of a glycoprotein
contained in certain food. In such cases tastes of known substances are altered. After
exposing the tongue to a berry, known as the miracle fruit, acids taste as if they have been
sweetened. Such effects are of interest in any study of taste receptor mechanisms and are
generally temporary.
Venous Taste
Venous taste is a phenomenon that occurs as the result of stimulation of receptor sites
that are on the bottom of the taste cell (i.e., below the microvilli). A sweet taste is
perceived in about 13.5 seconds after saccharin is injected into a vein. Similarly,
dehydrocholic acid will produce a bitter taste. This may be the origin of taste sensations
reported during chemotherapy.
Peripheral Nerves
Chorda Tympani
The chorda tympani nerve is most commonly involved in taste disorders and is identified
by taste loss on the anterior two thirds of the tongue. Acute or chronic otitis media is the
most common pathology of the middle ear. Although this source of taste damage was
well known in the nineteenth century, it has only recently been recognized as a modern
source of damage to the taste system. Paradoxically, most adults with histories of otitis
media as children do not suffer taste loss as a result of this damage. Rather, they
experience enhanced tastes from some stimuli (23). This may be due, in part, to increases
in the number of taste buds per fungiform papilla and release of inhibition as the result of
chorda tympani damage.
The viral involvement of the facial nerve that can occur in such disorders as Bell palsy or
Ramsay Hunt syndrome is associated with taste dysfunction and unilateral facial
paralysis. In most cases taste dysfunction is noted before the development of the facial
paralysis. Facial paralysis occurs in about 10% of patients with Lyme disease, so
observations of taste loss in this population are expected (36).
Middle ear or mastoid surgery, especially with facial recess exposure, can produce either
temporary or permanent taste loss. Bull (37) evaluated 126 cases in which the chorda
tympani nerve was cut in the course of stapedectomy. Cutting the nerve rendered the
ipsilateral anterior tongue completely devoid of taste.
When the chorda tympani is severed peripheral to the cell bodies in the geniculate
ganglion, Wallerian degeneration would be expected to move from the site of damage
toward the periphery. However, the effects on taste buds vary by species. In humans, the
lingual nerve appears to sustain fungiform papillae so the tongues of individuals in whom
the chorda tympani has been severed do not look abnormal (Janjua and Schwartz,
unpublished observations).
Infectious processes in the oral cavity rarely produce taste loss, but neoplastic
involvement of the floor of the mouth, submandibular space, or an infratemporal fossa
lesion may produce such symptoms. A more noticeable symptom of disease in these
regions would be tongue numbness, because the lingual nerve would also be involved.
Isolated unilateral tongue numbness in the absence of taste loss indicates a trigeminal
nerve lesion. In the absence of oral cavity pathology and tongue numbness, involvement
of the chorda tympani in the temporal bone or the nervus intermedius in the
cerebellopontine angle must be considered.
Nervus Intermedius
The nervus intermedius is central to the cell bodies in the geniculate ganglion. Thus, if
this nerve is cut, Wallerian degeneration would be expected to move from the cut toward
the central nervous system, not transganglionically toward the periphery. Neoplastic
processess such as acoustic neuroma, meningioma, or facial nerve neuroma are the most
common causes of nervus intermedius dysfunction. This is supported by examining
patients after unilateral acoustic tumor surgery in which there were no differences in
number of fungiform papillae or number of taste pores per fungiform papillae between
the operated and unoperated sides.
Glossopharyngeal Nerve
Trauma to the lingual or pharyngeal branches of cranial nerve IX can occur after
tonsillectomy, uvulopalatopharyngoplasty, or any insertion of a deep mouth gag where
the base of tongue is compressed and the lateral pharyngeal wall is manipulated or
stretched. Neck masses in the high jugular space (carotid body tumors, squamous cell
carcinoma, deep neck abscess) may alter ninth-nerve function. Following the IX nerve
more cephalad, lesions directly involving the skull base at the jugular foramen (e.g.,
glomus jugulare, schwannoma, squamous cell carcinoma) will compromise taste function
and will be associated with other cranial nerve neuropathies. Vernet syndrome occurs
when jugular foramen lesions paralyze all nerves that traverse the jugular foramen (IX,
X, and XI). Along with taste disturbance, there is the loss of sensation in the distribution
of cranial nerves IX and X, paralyzed ipsilateral pharyngeal wall and vocal cord, and
ipsilateral shoulder drop. When tumor extends below the skull base or deeper into the
foramen magnum, cranial nerve XII may also be involved, causing ipsilateral tongue
paralysis and occasional fasciculations. This is termed Collet syndrome. Villaret
syndrome involves a lesion extending out of the jugular foramen, which causes
sympathetic trunk compromise and ninth to twelfth nerve paralysis. Such patients exhibit
ptosis, miosis, and occasionally enophthalmos. Schwannomas especially can begin
intracranially in the cerebellopontine angle to produce similar symptoms and nerve
dysfunction.
Central Nervous System
Unilateral pontine hemorrhage and unilateral damage to the rostral insular cortex (38)
give rise to unilateral taste loss on the same side as the injury. These data played an
important role in the conclusion noted previously that taste projects ipsilaterally. The
incidence of taste loss in head trauma is reported to be 0.4% to 0.5% (39). However, the
incidence may be much higher than this, because head trauma can produce spatially
discrete taste losses that go unnoticed for the reasons discussed previously. These taste
losses are probably the result of a variety of types of damage, but little is known at this
time.
Cumulative Taste Loss
It is important to note that damage to a localized part of the taste system may
occasionally lead to taste loss that is much more severe than the damage would seem to
warrant. This would be expected as a result of the fact that a considerable amount of
damage can occur without any changes in the everyday taste experience of the patient
(see Interactions Within the Nervous System, above). For example, on rare occasions,
tonsillectomy produces a virtually total taste loss even though only the glossopharyngeal
nerve is especially vulnerable during surgery. In such cases, the patient might have had
severe seventh-nerve damage (e.g., as a result of chronic otitis media) before surgery but
not have noticed it because of the release-of-inhibition phenomenon discussed
previously. Damage to cranial nerve IX during surgery would then leave the patient with
no reserves, and the taste loss experienced would be much more extensive than would
seem to be accounted for by the surgery alone.
PHANTOMS FROM DAMAGE TO PERIPHERAL STRUCTURES
The mechanisms by which damage to a structure produces phantoms are not fully
understood. We present here an overview about taste phantoms that we have developed
as a result of experiments with anesthesia and observations of patients. We note that
phantoms associated with damage to sensory nerves provide a paradox. Marbach (40)
expressed this well in an article on phantom tooth pain: Many of these pain conditions are
puzzling because injury to a sensory nerve is expected to result in some degree of
anesthesia or paresthesia, not chronic pain. The paradox is intriguing. Why would nerve
injury that blocks conduction increase rather than decrease sensation? If we substitute
taste for pain, we find ourselves in complete agreement. We cannot explain this paradox,
but we will document its consequences for patients.
Peripheral Nerves
Chorda Tympani
As we noted previously, despite the fact that Bull's (37) patients lost taste in the area
innervated by the cut chorda tympani, their most common complaint was a metallic taste,
less frequently described as a bitter or salty taste. Over half of these phantoms were not
localized to the area innervated by the severed chorda tympani but rather were felt all
over the mouth or just on the tip of the tongue. The remaining phantoms were localized to
the side of the mouth on which the chorda tympani was cut. Bull (37) noted that in 100
patients in whom the nerve had been stretched rather than cut, the symptoms were less
noteworthy, but metallic phantoms still occurred. Bitter and metallic phantom tastes have
been reported when the chorda tympani nerve was stretched as a result of dislodgement
of ossicular replacement prostheses. Washing the ear canal has been reported to produce
a metallic taste phantom and touch sensations in some subjects.
Nervus Intermedius
The nervus intermedius often must be sacrificed to permit the removal of an acoustic
neuroma. Phantoms (usually salty) have been reported by 13 of 26 patients we
interviewed after acoustic neuroma surgery. In patients available for tests, the phantoms
could not be rinsed away with water and intensified after anesthesia of the mouth.
One of the most interesting features of the taste phantoms associated with surgery for
acoustic neuromas is their duration. Patients reported that the phantoms lasted about 6
months and then faded. This is in contrast to the persistence of phantoms noted by some
patients whose chorda tympani nerves were cut.
Glossopharyngeal Nerve
Loss of function of the circumvallate papillae (cranial nerve IX) is rare but can occur
after tonsillectomy or surgery to the hypopharynx. Patients report a bitter taste phantom
that increases with topical anesthesia. This finding supports the idea that cranial nerve
VII normally inhibits cranial nerve IX.
Epilepsy
Taste auras in temporal lobe epilepsy are rare but do occur. Hughlings Jackson described
a patient who experienced a metallic taste before a seizure. In a remarkable series of 718
patients, Hausser-Hauw and Bancaud (41) found 30 patients with taste hallucinations. In
addition, brief taste hallucinations were produced in seven patients with electrical
stimulation. The most common quality reported was bitter. In a number of cases, the
quality described may reflect olfactory rather than taste phantoms.
CAPSAICIN: A NOVEL WAY TO TREAT ORAL PAIN
Capsaicin stimulates oral pain, as all chili pepper aficionados know. However, capsaicin
also has the unique property of desensitizing pain receptors and has been utilized as an
analgesic for a variety of sources of dermal pain, albeit with mixed success. Study of the
properties of capsaicin desensitization in the mouth led to the insight that capsaicin would
act as an analgesic on oral mucosal tissue far better than on nonmucosal tissue. This has
been supported in clinical settings (42).
EFFECTS OF AGE ON THE SENSE OF TASTE
The belief that taste dims with age is common but not supported by a careful review of
the psychophysical literature. One of the reasons that this belief survives is because some
of the suprathreshold scaling studies have been conducted with methodologies (see
Evaluation of the Taste Sense, above) that are open to criticism. In our view, the most
conservative summary of this work is as follows (30): Taste is much less affected by age
than is olfaction. Across the standard stimuli, sucrose is the most robust, and citric acid
and quinine are the most likely to show loss, but that loss is not great.
EFFECTS OF CANCER AND CANCER THERAPIES ON THE SENSE
OF TASTE
In 1975, DeWys and Walters (43) reported that a subset of cancer patients had
abnormally low taste thresholds for the bitter compound urea. This was invoked to
explain meat aversion on the grounds that meat contains bitter compounds that would
cause aversions in the supersensitive patient. This result was widely cited but was wrong
due to a serious statistical error. Subsequent research focused on the effects of
chemotherapy and radiation therapy on taste showed that some patients lost taste (often
temporarily) and other patients experienced taste phantoms as the result of these therapies
(44).
EFFECTS OF MEDICATIONS ON THE SENSE OF TASTE
Many medications have been associated anecdotally with loss of taste or with taste
phantoms (45); however, few have been evaluated with careful clinical studies. More
work in this area would be valuable, because these effects may have important
implications for taste physiology and for patient care. Anecdotal observations are very
valuable as an indication of where taste investigators should focus study but rarely
provide insights into mechanism.
When medications are associated with phantom tastes, the clinician should first evaluate
the possibility that the medication itself is the source of the taste. Medications taken
orally enter the blood and from there may enter crevicular fluid and saliva. In addition,
they may be tasted from blood directly (see Venous Taste, above). Medications used in
chemotherapy provide excellent examples (46). When drugs are tasted in this way, the
taste sensitivities of the patient may play a role in the detection of the drug. For example,
those most genetically sensitive to bitter taste would be expected to taste more bitterness
in medications.
TASTE CHANGES WITH DISEASE
Some diseases are believed to affect the sense of taste (47). The clearest cases for effects
on taste occur with renal disease, diabetes, and depression.
Renal disease has been associated with both taste loss and taste phantoms (metallic,
bitter). Improvement occurs with dialysis, which suggests a role for the uremic toxins that
accumulate with kidney dysfunction (48). The metallic/bitter phantoms may reflect the
presence of these toxins in the mouth and/or blood.
Diabetes causes neuropathies that involve the taste nerves and other nerves. However,
work with subjects with a family history of diabetes suggests a deficit specific to glucose
in addition to the general taste neuropathy (12). This work may provide a genetic marker
for a predisposition to diabetes. However, it is also of considerable significance for our
understanding of sweet receptors. A specific deficit for glucose suggests that the receptor
mechanism for glucose must be different from those of other sugars.
There is some evidence of reduced taste function in some depressed patients. In addition,
there is also some evidence of an association between depression and PTC/PROP tasting
(49).
The literature on taste disorders and disease is complicated by the use of psychophysical
procedures that have come to be viewed with some concern. The older literature used
threshold measures almost exclusively, which limits the value of those studies in the
modern era.
COPING WITH TASTE DISORDERS
Unfortunately, in most cases even if the cause for the taste disorder is known, there are
few effective therapies. Thus, the primary aim of the clinician may often be to help
patients cope with these disorders (50). Patients with taste disorders cope via cognitive
adaptations just as those experiencing other chronic disorders. They find meaning in the
disorder, find benefits in it, and make comparisons with others who are less fortunate.
Patient's attempts to find the cause of the disorder play a role in coping. Blaming oneself
for the disorder is associated with better adjustment.
Some types of support for patients are clearly not helpful. The disorder should not be
trivialized, nor should it be attributed to psychological causes. Psychological support,
however, may be of value to help the patient deal with the stress produced by the
symptoms.
ACKNOWLEDGMENTS
Supported in part by National Institutes of Health grants DC00283 and DC03003. We
thank Ralph Norgren and Thomas Pritchard for their contributions to Figure 45.1 and to
the discussion of the central nervous system anatomy of taste.

HIGHLIGHTS
There are four genuine taste qualities: salty, sweet, sour, and
bitter. Flavor, which is often mistakenly called taste, is the
combination of taste and smell
The pleasure or displeasure associated with taste appears to be
hard wired into the brain and is present at birth.
There are genetic differences in the abilities of segments of the
population to taste certain bitter or sweet substances.
There are two kinds of taste disorders: taste loss, which can be
partial (i.e., hypogeusia) or total (i.e., ageusia), and taste
phantoms, which are tastes experienced in the absence of overt
stimulation (i.e., dysgeusia).
Taste remains robust over the lifespan, but it is affected by
many diseases and injuries. Elderly persons have an increased
probability of having had one or more of these diseases and
injuries simply because they have been alive for more years.
Many of the elderly have intact taste senses, but there are also
more taste disorders among them than the young.
Changes in taste threshold do not necessarily predict changes in
suprathreshold measures. Because the more important symptom
in patients is alterations in suprathreshold taste abilities, clinical
evaluation should rely on suprathreshold measures.
Taste receptor cells undergo continual turnover and are
replaced from basal cells.
Taste buds on the tongue are found on the fungiform papillae,
which are innervated by the chorda tympani nerve (VII); the
circumvallate and foliate papillae, which are innervated by the
glossopharyngeal nerve (IX); the margin between the hard and
soft palate, innervated by greater superficial petrosal nerve
(VII); and the laryngeal surface of the epiglottis, innervated by
the vagus nerve (X).
Taste fibers from cranial nerves VII, IX, and X terminate in the
rostral nucleus solitarius in the medulla. From there, the taste
pathway travels ipsilaterally to the ventroposteromedial nucleus
in the thalamus and to the cortex.
The taste system functions by a balance of excitatory and
inhibitory neural messages. This circuitry keeps taste
perception relatively normal, even if large parts of the taste
system are damaged.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

46 STOMATITIS
Head & Neck SurgeryOtolaryngology
46




STOMATITIS
STEVEN B. ARAGON
BRUCE W. JAFEK
STEVE JOHNSON

S.B. Aragon and B.W. Jafek: Department of Otolaryngology, University of Colorado School of Medicine,
Denver, Colorado.
S. Johnson: University of Colorado Health Sciences Center, Denver, Colorado.


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Differential Diagnosis
Treatment
Pemphigus Vulgaris
Etiology
Clinical Features
Histopathology
Treatment
Erythema Multiforme
Etiology
Clinical Features
Stevens-Johnson Syndrome
Toxic Epidermal Necrolysis
Histopathology
Differential Diagnosis
Treatment
Lichen Planus
Etiology
Clinical Features
Histopathology
Differential Diagnosis
Treatment
Candidiasis
Etiology
Clinical Presentation
Histopathology
Treatment
Recurrent Aphthous Stomatitis
Etiology
Clinical Features
Histopathology
Differential Diagnosis
Treatment
Mucositis
Etiology
Acquired Immunodeficiency Syndrome
Chapter References
Stomatitis is inflammation of the oral mucosa. The inflammation may involve the buccal
mucosa, attached or unattached gingiva, labial mucosa, palate, tongue, and floor of the
mouth. This chapter reviews the common viral and fungal causes of stomatitis and
delineates the immunologic patterns and types of vesiculobullous lesions a physician may
encounter. The impact of the human immunodeficiency virus (HIV) on patient illness and
care has been dramatic, and the oral manifestations of HIV and acquired
immunodeficiency syndrome (AIDS) are important for proper identification and
treatment of the disease. The most common oral manifestations of HIV and AIDS are
reviewed in this chapter.
HERPES
The herpes simplex virus (HSV) is a large enveloped icosahedral virus that contains
linear double-stranded DNA. More than 50 herpesviruses have been described; however,
most oral lesions are the result of type I (HSV-I) and occasionally type II (HSV-II).
Etiology
HSV-I is more commonly associated with oral lesions, and genital lesions are usually
associated with HSV-II. However, HSV-II also may cause oral lesions, and as many as
15% to 30% of primary genital HSV infections may be due to HSV-I. Concurrent oral
and genital infections may occur with HSV-I or HSV-II. From 0.75% to 10% of adults
periodically shed infectious HSV in saliva, and asymptomatic genital shedding
commonly occurs. HSV infection of fingers (herpetic whitlow) may lead to covert spread
of infection from health care workers to seronegative patients. The lipid envelope of HSV
is necessary for infectivity and is acutely susceptible to drying, disinfectants, and
solvents. Nevertheless, HSV can survive for several hours on nonmucosal surfaces and in
fluids. HSV transmission is almost always through intimate contact with infected body
fluids (1). Primary infection typically occurs through penetration of the oral mucosa, and
only a small percentage of persons will show signs and symptoms of systemic disease at
this time. The usual incubation time is 7 days, but the range is 1 to 26 days. The virus
migrates along the periaxonal sheath of the trigeminal nerve to the trigeminal ganglion,
where it lies dormant until reactivation. Reactivation of the virus in the latent phase has
been attributed to a variety of stimuli, including sun exposure, emotional stress, and
trauma.
Clinical Features
The two main clinical manifestations of HSV infections are primary herpetic
gingivostomatitis and recurrent or secondary HSV infections. Primary herpetic
gingivostomatitis usually is seen in seronegative children and occasionally in adults with
no prior HSV exposure. About 1% of the population manifests the full clinical picture of
herpetic gingivostomatitis. Stomatitis and pharyngitis are the most frequent clinical
manifestations of primary HSV-I infections and occasionally of HSV-II infections.
Infection may be accompanied by fever, arthralgia, malaise, headache, cervical
lymphadenopathy, oral ulcers, and gingivitis. Adults with primary gingivostomatitis are
generally much more symptomatic than children. Crops of small vesicles can occur on
any mucosal surface (e.g., tongue, lips, palate, buccal mucosa, pharynx), as opposed to
the recurrent form of the disease, in which lesions are confined to the hard palate and
gingiva. The small vesicles usually rupture within 24 hours, leaving an erythematous
border with a gray covering membrane. New lesions continue to appear for 7 days and
heal in 7 to 14 days without scarring. The gingiva may appear extremely red and swollen
without necrosis of the interdental papilla. After 7 to 14 days, the primary infection has
run its course and the virus has invaded the trigeminal nerve ganglia, where it remains
latent until reactivation.
In the United States, serologic studies have shown that up to 60% of children under the
age of 10 years have been exposed to the virus; by the age of 50 years, the incidence
increases to as high as 90%. Recurrence rates for oral HSV infection range from 16% to
45%. Most persons with recurrent infections have experienced prior subclinical primary
infections. Reactivation of the virus in its dormant state may be triggered by ultraviolet
light, stress, fever, cold, fatigue, immunosuppression, trauma, menses, and chapped lips.
The lesions usually are localized to the mucocutaneous junction of the lips (i.e., herpes
labialis) and occasionally intraorally or the fixed keratinized mucosa (i.e., hard palate and
attached gingiva). The size of the lesion corresponds to the sensory field of the infected
neuron. In up to 60% of cases, prodromal symptoms at the site of the lesion precede
development of lesions. Prodromal symptoms include burning, itching, tingling, and pain
at the site where the lesion will occur. Classically, crops of painful ulcers appear,
ulcerate, and coalesce to form superficial ulcers (Fig. 46.1; see also Color Plate 5
following p. 370). These lesions usually heal in 1 to 2 weeks without scarring. Other
types of lesions associated with reactivation of HSV-I include aborted lesions, which may
consist only of prodromal symptoms and erythema, or prodromal symptoms with
development of a papule that does not ulcerate and crust over. The time of greatest
infectivity and pain is when the lesion first ulcerates; the shedding of infectious virus
particles and the pain decline rapidly as the lesion develops a crust.

FIGURE 46.1. Oral herpes simplex virus ulceration with
erythematous border. (Courtesy of Dr. Robert O. Greer.)
(See also Color Plate 5 following p. 370.)



Histopathology
Herpetic vesicles are located intraepidermally and are formed by ballooning
degeneration of epithelial cells. The infected epithelial cells may contain a single
nucleus, or infected cells may fuse to form multinucleated giant cells. Cytologic smears
obtained early in the infection show a nucleus that is homogeneous and glassy with the
nuclear material pushed out to the perimeter of the cell. The cytologic characteristics are
lost shortly after the vesicles have ruptured. HSV infections elicit a humoral and cellular
immune response. Cellular immunity is more important in restricting viral replication and
spread but is unable to eliminate the virus from the trigeminal ganglia. Based on the
importance of the cellular immune response, it has been postulated that recurrent
infection may be due to transient immunodepression.
Differential Diagnosis
The diagnosis of primary herpetic gingivostomatitis is usually clearly evident from the
clinical features. The clinical suspicion can be confirmed by viral cultures (2 to 4 days are
required for positive identification). Species identification can be accomplished by the
use of monoclonal antibodies or by DNA hybridization techniques. Primary
gingivostomatitis can be confused with minor aphthous ulcers, erythema multiforme, or
acute necrotizing ulcerative gingivitis (Vincent infection). Aphthous ulcers do not go
through a vesicular stage and usually are composed of a single oval ulcer located on
unattached gingiva. The oral ulcers of erythema multiforme are much larger, do not have
a vesicular stage, and less commonly affect the gingiva. Vincent infection does not have a
vesicular stage; its lesions are limited to the gingiva, and it involves necrosis of the
papillary and marginal gingiva.
Treatment
In immunocompetent hosts, oral HSV lesions usually are managed with supportive care
with proper hydration, analgesics, and antipyretics. Antibiotics may be used to prevent or
treat secondary bacterial infections. Antiviral medications active against HSV are
available but generally are reserved for immunocompromised patients. Acyclovir has
been established as the gold standard for anti-HSV drugs. It is a potent acyclic guanosine
derivative that is a highly selective viral DNA polymerase and therefore has no effect on
normal host epithelium. Acyclovir is well tolerated and has no serious side effects (2). In
the immunocompetent patient with primary herpetic gingivostomatitis, 100 to 200 mg of
acyclovir is given five times a day. Recurrent herpes (i.e., herpes labialis) may be treated
topically with a 5% acyclovir cream applied five times per day. If used early in the
prodromal phase, topical acyclovir may shorten or abort the herpes labialis recurrence.
Long-term use of oral acyclovir, 400 mg twice daily or 200 mg four times daily,
significantly suppresses recurrent herpes labialis and does not have significant side
effects. Other anti-HSV medications are also available. Famcyclovir has antiviral activity
similar to acyclovir, but it has not been shown to be clinically superior to acyclovir.
Valacyclovir is the 1-valyl ester of acyclovir that breaks down in the body to acyclovir
and the natural amino acid lvaline; its greatest benefit is that its oral availability is much
greater than the poorly absorbed oral acyclovir. Oral dosing of valacyclovir produces
plasma levels of acyclovir that are similar to those of intravenous acyclovir. Foscarnet
can be used to treat acyclovir-resistant strains of HSV.
Recurrent HSV infections in immunocompromised patients are more severe and last
longer than in the general population. Treatment of this population is addressed at the end
of this chapter.
VARICELLA ZOSTER
Varicella-zoster virus (VZV) is a member of the herpesvirus family. The primary
infection caused by VZV in seronegative persons is varicella (chickenpox). The
secondary disease is known as herpes zoster (shingles) and is the result of reactivation of
latent VZV.
Varicella
Etiology
Varicella transmission is believed to be predominantly by inspiration of contaminated
respiratory droplets and less commonly by direct contact. The incubation period is about
2 weeks, during which time the virus proliferates. The resulting viremia and
dissemination to the skin and other organs produce the manifestations of the disease.
Clinical Features
Headache, fever, chills, and malaise may accompany the rash, which involves the trunk,
head, and neck. The rash develops into a vesicular eruption that becomes pustular and
eventually forms a superficial crust. The limited infection lasts 7 to 10 days. Repeated
waves of viremia may lead to successive crops of vesicles. The oral mucosa, most
commonly the buccal mucosa, palate, and pharynx, may demonstrate small vesicles,
which quickly lead to ulcers with an erythematous margin. These ulcers may resemble
aphthous ulcers, but they are less painful.
Treatment
Treatment is generally supportive in immunocompetent pat-ients. Immunocompromised
patients may require the use of virus-specific drugs, such as systemically administered
acyclovir and vidarabine. A vaccine is now available to prevent infection with VZV, but
it remains controversial. In all patients with varicella, corticosteroids are generally
contraindicated.
Zoster
Etiology
VZV may travel along sensory nerves to the sensory ganglion during the primary
infection. Reactivation of latent VZV is uncommon, but the incidence is increased in
immunosuppressive states such as malignancy, trauma, drug therapy, radiation therapy,
or high-dose steroid treatment.
Clinical Features
Disease occurs primarily in adults and immunocompromised persons and tends to cause
postherpetic neuralgia. The sensory nerves of the head, neck, and trunk are most
commonly affected.
Fever and malaise accompany the pain and tenderness along the course of the involved
nerve, usually unilaterally in a dermatomal pattern. Several days after the prodromal
symptoms, a fine maculopapular rash develops along the involved dermatome. The rash
quickly becomes vesicular, pustular, and then ulcerative. Remission usually follows in
several weeks. Involvement of the mucous membranes usually occurs after the skin
lesions, but oral lesions occasionally may occur without skin involvement. The branches
of the trigeminal nerve (most commonly ophthalmic) often are affected. Involvement of
the facial and auditory nerves results in the Ramsey Hunt syndrome, where there is facial
paralysis, tinnitus, vertigo, and deafness with vesicles to the external ear. By far the most
common complication of herpes zoster is postherpetic neuralgia, which is experienced as
intractable pain.
Treatment
Therapy for immunologically intact patients has generally been supportive; however,
recently it was shown that acyclovir, 800 mg five times a day for 7 days, or famcyclovir,
500 to 700 mg three times per day for 7 days, significantly reduces the duration of
postherpetic neuralgia. Topical antiviral drugs may be helpful if used early in the course
of the disease. Topical capsaicin may provide some pain relief by interfering with
substance P-mediated pain transmission. Immunocompromised patients may require
systemically administered famcyclovir, vidarabine, or interferon.
DESQUAMATIVE GINGIVITIS
Desquamative gingivitis is a clinical entity characterized by diffuse erythematous
desquamation, ulceration, and possible bullae formation affecting the free and attached
gingiva (Fig. 46.2; see also Color Plate 6 following p. 370). There is a female
predilection, usually occurring after the age of 30 and most commonly in the sixth or
seventh decades. The extent of gingival involvement varies. Occasionally, the erythema
predominates with minimal desquamation, and in other cases, the epithelium can be
easily peeled away from nonulcerated areas. Desquamative gingivitis is a manifestation
of several diseases (Table 46.1). Erosive lichen planus, cicatricial pemphigoid, and
pemphigus vulgaris are the diseases underlying most of the cases. Also implicated are
psoriasis, bullous pemphigoid, dermatitis herpetiform, and drug reactions. Because these
diseases can present with the common picture of desquamative gingivitis, an incisional
biopsy usually is required to make the definitive diagnosis.

FIGURE 46.2. Desquamative gingivitis showing diffuse
erythematous desquamation and ulceration of the gingiva.
(See also Color Plate 6 following p. 370.)



TABLE 46.1. DISORDERS CAUSING
DESQUAMATIVE GINGIVITIS



Direct and indirect immunofluorescence tests are helpful in differentiating many of the
clinically similar vesiculobullous lesions. Direct immunofluorescence is used to detect
the presence of antibody or complement bound to tissue samples. Fluorescein-labeled
antibodies to human immunoglobulins and complement are added to the tissue sample,
where they bind to IgG, IgA, IgM, and complement. The immunofluorescence patterns
may further define the different entities (Fig. 46.3 and Fig. 46.4) and may be limited to
the epithelial intercellular substance, as in pemphigus vulgaris, or to the basement
membrane, as in cicatricial pemphigoid. The fresh biopsy specimen must be placed in a
holding solution (e.g., Michel solution) for transportation, allowing the fluorescein-
labeled antibodies to incubate with the biopsy tissue. Indirect immunofluorescence
measures the circulating antibodies in a patient's serum. Antibodies in the patient's serum
react with normal control tissue, which then is labeled with fluorescein-labeled antibodies
to serum antibodies bound to the control tissue. Examples of positive indirect
immunofluorescence identification include pemphigus and bullous pemphigoid.

FIGURE 46.3. Direct immunofluorescence limited
primarily to the basement membrane in cicatricial
pemphigoid.



FIGURE 46.4. Direct immunofluorescence limited to the
epithelial intercellular substance as seen in pemphigus
vulgaris.



LUPUS ERYTHEMATOSUS
Etiology
Lupus is considered the result of an autoimmune process in which the humoral and cell-
mediated mechanisms of the immune system are affected. This autoimmune process is
thought possibly to be influenced by genetic or viral factors. A large number of
autoantibodies against various cellular antigens in the nucleus and cytoplasm of cells
have been identified in serum and in tissue bound to antigens. Antigen-antibody
complexes found in serum are responsible for the multiple organ manifestations. The
immune complexes are not removed entirely by the reticuloendothelial system and persist
to become deposited in the subepithelial layer, initiating an inflammatory reaction.
Clinical Features
Lupus erythematosus can be divided into three subsets: acute systemic lupus
erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE), and chronic
discoid lupus erythematosus (DLE). Any of these may involve the oral mucosa.
DLE most often affects women in their third to fifth decades of life. It is the least
aggressive form of lupus, and patients are usually asymptomatic. The cutaneous and
mucosal surfaces (e.g., face, oral mucosa, back, and extremities) are affected without
visceral involvement. The skin lesions appear as elevated erythematous plaques with
hyperpigmented margins. The lesions grow peripherally with central healing and scar
formation, leaving hypopigmented areas or areas of permanent alopecia in hair-bearing
areas. Oral manifestations are found in about 25% of the patients with DLE. The buccal
mucosa, gingiva, labial mucosa, and vermilion borders are the most commonly involved
areas. Erythematous plaques or erosions may develop into superficial painful ulcerations.
Delicate white keratotic striae are often seen radiating from the margin of the lesion.
Keratotic papules also may be seen in the lesions. Diagnosis of oral lesions may not be
obvious based on their clinical appearance but are suspect in the presence of cutaneous
lesions. Ocular manifestations in the form of erythematous plaques may involve the
lower lid, which may result in erosion of the lid margin and development or ectropion
and symblepharon. Although unlikely, a small possibility exists for the progression of
DLE into SLE, or DLE may be the initial presentation of SLE.
In SCLE, the cutaneous lesions appear as annular or papulosquamous lesions, which
persist for weeks or months and heal without scarring. Lesions most commonly occur in
sun-exposed areas. Oral manifestations are similar to those seen in DLE. Mild systemic
symptoms also may exist. Several antibodies to cytoplasmic components may be found in
the serum. Anti-Ro Sjgren syndrome A antibody (SS-A) may be found in SCLE and
Sjgren syndrome. Anti-La (SS-B) is another such antibody, which is found less
commonly in both diseases. Antinuclear antibody (ANA) occasionally may test positive
if an extremely sensitive testing system is used. In general, SCLE is considered
intermediate between DLE and SLE in severity, with little chance of progression to SLE.
SLE is characterized by multiorgan system involvement with mild skin and oral lesions.
Oral lesions are estimated to occur in about 40% of patients with SLE. Multiple
antibodies against nuclear and cytoplasmic antigens (ANA, SS-A, SS-B) produce
antigen-antibody complexes in serum or target tissues, resulting in the systemic
manifestations. Skin involvement produces the classic butterfly rash on the malar
processes and bridge of the nose. The face, hands, and trunk may be involved, usually
without scarring. The initial symptoms of fever, weight loss, and malaise are followed by
joint, kidney, heart, and lung involvement. Renal involvement may result in
glomerulonephritis, which is the most common cause of death in SLE patients. The oral
lesions are similar to those seen in DLE. Nonkeratinized mucosa, which covers the soft
palate, lips, cheeks, and alveolar process as far as the gingiva, is predominantly involved
by chronic discoid lesions, and the keratinized mucosa on the hard palate and gingiva is
involved by acute lesions. The oral lesions found in SLE appear to be the result of
vacuolar degeneration of basal keratinocytes, not due to vasculitis as are many of the
effects of lupus erythematosus.
The screening test for SLE is the fluorescent test for ANAs; the test is positive in more
than 98% of SLE patients. ANAs against single-stranded or double-stranded DNA, RNA,
nuclear proteins, and protein-nucleic acid complexes may result in a positive ANA test.
Histopathology
Consistent microscopic features of DLE include areas of hyperparakeratosis alternating
with areas of epithelial atrophy, liquefactive degeneration of the basal cell layer,
lymphocytic infiltration in superficial and deep connective tissue with perivascular
cuffing, follicular plugging and dilatation, and submucosal edema with vascular
dilatation. Diagnostically, the most important microscopic finding is the change in the
interface; basal cells appear to be the major target in skin and mucous membrane disease.
Although the histologic findings in SLE are similar to those in DLE, the lesions in SLE
reveal more severe degenerative disease and less evident inflammatory cell infiltrate. The
reaction in an older test, called the lupus erythematosus cell phenomenon, occurs when
the serum of an affected SLE patient is added to the buffy coat of normal blood. The
reaction consists of a rosette of neutrophils surrounding a pale nuclear lymphocytic mass.
The predilection for basement membrane immu-noglobulin and complement deposition
(i.e., lupus band) is present in cutaneous and mucosal lesions in DLE and SLE. The lupus
band test has a negative predictive value of 98%, sensitivity of 93%, specificity of 87%,
and a positive predictive value of 64% for SLE. For DLE, the negative predictive value is
32%, sensitivity 58%, specificity 87%, and positive predictive value 95%. This suggests
that the lupus band test is highly effective in ruling out non-SLE disease. Although the
lupus band test has a high positive predictive value for DLE, the clinical features and
histopathology are thought to be better in establishing disease. Direct
immunofluorescence for the basement membrane in nonclinically involved mucosal
tissue is positive in 24% and 3% of SLE and DLE cases, respectively. The direct
immunofluorescence assay for the basement membrane zone is positive in 42% and 50%
of SLE and DLE cases, respectively, for noninvolved conjunctiva. In SCLE, the
microscopic findings are similar to DLE but with less follicular plugging and dilatation,
hyperkeratosis, fewer mononuclear cells, and more epidermal atrophy. SCLE also has a
unique pattern of immunofluorescence of dustlike particles of IgG deposited in the
epidermis, subdermal region, and dermal cellular infiltrate in 32% of SCLE patients
biopsied.
Differential Diagnosis
Although lupus and lichen planus may exhibit striae, the striae of lupus erythematosus is
more subtle. Furthermore, lichen planus usually does not involve the anterior part of the
buccal mucosa without also involving the posterior surface or the mucosa of the palate
unless it presents extensively in the mouth. The ulcerations of lupus erythematosus may
resemble those of pemphigus vulgaris, cicatricial pemphigoid, erythema multiforme, and
adverse drug reactions. Clinical presentation and biopsy are usually sufficient to
differentiate lupus erythematosus from these entities. Furthermore, serologic testing for
ANA can establish or dismiss SLE, and the lupus band test can rule out non-SLE
conditions (Table 46.2).

TABLE 46.2. DIAGNOSIS



Treatment
Topical steroids usually are used for the treatment of DLE, and early treatment is
advisable before atrophy is permanent. Exposure to sunlight should be minimized in all
types of lupus erythematosus, and sunscreens that block both UV-A and UV-B should be
used. Intralesional steroid injections can be helpful. Antiinflammatory medications like
salicylates (2.4 to 3.6 g/day) are often used to treat the symptoms of fatigue, fever, and
arthralgias in SLE. Nonsteroidal antiinflammatory drugs (NSAIDs) such as
indomethacin, ibuprofen, naproxen, and tolmetin (Tolectin) also have been used to
suppress these symptoms but have not been shown to be superior to aspirin, and NSAIDs
may also complicate renal impairment due to SLE (2). Systemic steroids are indicated for
severe inflammatory states. Prednisone in daily doses of 10 to 20 mg or as high as 200
mg may be required and should be tapered to a minimal dose as soon as possible to
prevent the adverse side effects of steroids. Antimalarials (e.g., chloroquine,
hydroxychloroquine) are also effective in controlling SLE. Hydroxychloroquine, 200 to
400 mg/day, or chloroquine, 250 to 500 mg/day, is effective in controlling the cutaneous
manifestations of lupus erythematosus and also has a steroid-sparing effect. Ocular
toxicity is the main side effect of the antimalarials, and ophthalmologic examinations
should be performed every 6 months while the patient is taking these medications to
prevent ocular complications. Cytotoxic agents (e.g., azathioprine, cyclophosphamide)
are used in treatment of severe SLE with nephritis. Isotretinoin 1 mg/kg/day produces
dramatic results, but recurrence is rapid after withdrawal of medication. Methotrexate in
the dose of 7.5 mg/day is effective in the treatment of patients with SLE who are resistant
to corticosteroid (3) (Table 46.3).

TABLE 46.3. TREATMENT



CICATRICIAL PEMPHIGOID
Etiology
Cicatricial pemphigoid is a chronic blistering disease of the mucous membranes and
occasionally the skin. It also has been known as ocular pemphigus, benign mucous
membrane pemphigoid, mucosal pemphigoid, and childhood pemphigoid. It is an
autoimmune disease with antibodies to the lamina lucida and occasionally to the lamina
densa of the basement membrane zone. It is thought that antibodies bind to antigen in the
lamina lucida, and complement gets activated. Complement components are chemotactic
that then attract inflammatory cells that release enzymes that degrade the lamina lucida.
The end result is separation at the lamina lucida between the basal lamina and the
overlying epithelium forming subepidermal blisters.
Clinical Features
Cicatricial pemphigoid is a disease that mostly affects middle-aged and elderly persons
with a mean age at onset of 66 years. Females are affected twice as often as men.
Cicatricial pemphigoid may present as a bulla that ruptures, forming an ulceration or
erosion that heals slowly and may result in scarring. The oral mucosa is almost always
involved and may be the only site affected for years. It most commonly affects the
attached gingiva, presenting as desquamative gingivitis with a diffuse or patchy
erythematous appearance (Fig. 46.5; see also Color Plate 7 following p. 370). The buccal
mucosa, palate, alveolar ridge, tongue, and lips may also be involved. A gentle rubbing of
the uninvolved mucosa denudes the surface epithelium, producing a vesicle or ulcer
(positive Nikolsky sign). The conjunctiva is the next most commonly affected site (50%
to 70% of patients). Conjunctival lesions usually begin as chronic intractable
conjunctivitis with fibrosis beneath the conjunctival epithelium. The fibrosis can lead to
fusion of the palpebral and scleral conjunctiva (symblepharon), fusion of the inferior and
superior palpebral conjunctiva (ankyloblepharon), inversion of the eyelid margins
(entropion), inversion of lashes onto the corneal surface (trichiasis), decreased tear
formation, and blindness. Less commonly affected mucosal surfaces include esophageal,
nasal, laryngeal, pharyngeal, rectal, and genital mucosa. Cutaneous surfaces are rarely
involved. The most frequent sites include the face, neck, and scalp. These cutaneous
lesions may occur as bullae that heal with minimal scarring or as areas of erythema with
recurring blisters that often heal with scarring.

FIGURE 46.5. Cicatricial pemphigoid showing diffuse
and patchy erythematous lesions of the attached gingiva.
(Courtesy of Dr. Robert O. Greer.) (See also Color Plate
7 following p. 370.)



Histopathology
Biopsy of these lesions reveals subepithelial clefting from dissolution of the lamina
lucida of the basement membrane zone, with no evidence of acantholysis or degenerative
epithelial changes (Fig. 46.6). The lamina propria is variably infiltrated with lymphocytes
and plasma cells. Direct immunofluorescence demonstrates a linear pattern of IgG
fluorescence at the basement membrane in lesional and normal-appearing perilesional
tissue. IgA also may be detected in a similar pattern; however, if only IgA is detected,
some investigators believe this is a separate disease, termed linear IgA disease. Various
complement components also may be detected in a similar pattern, including C3, C4, and
C1q. Direct immunofluorescence has been positive in 96% and 48% of oral and
cutaneous lesions, respectively. Indirect immunofluorescence is usually negative for
circulating and basement membrane antibodies, but IgG and IgA assays are occasionally
(20% to 25%) positive. It has been suggested that because cicatricial pemphigoid is a
relatively localized disease, unlike bullous pemphigoid, only a small quantity of antibody
is produced, and all of it binds to the basement membrane zone and is therefore not
detected in the serum. When indirect immunofluorescence is performed using salt-split
skin specimens, many more patients test positive for circulating antibodies (11/11 in one
study). Immunoblotting assays have revealed that some patients with cicatricial
pemphigoid have antibodies to the anchoring filament protein called epiligrin.

FIGURE 46.6. Subepithelial clefting seen in cicatricial
pemphigoid.



Differential Diagnosis
Cicatricial pemphigoid is clinically similar to several of the other vesiculobullous
diseases, including erosive lichen planus, pemphigus vulgaris, bullous pemphigoid, and
erythema multiforme. Diagnosis is therefore based on the histologic and
immunofluorescence studies and clinical presentation. Some researchers believe
cicatricial pemphigoid and bullous pemphigoid may be variants of the same disorder
(Table 46.2).
Treatment
Cicatricial pemphigoid is difficult to control if multiple mucous membranes are involved
or if it is associated with concomitant medical problems. Potent topical steroids
(betamethasone, fluocinonide) may be used for mild and localized oral lesions. Occlusion
of the topical steroids may enhance the response. For gingival disease, occlusion can be
accomplished by using a flexible custom-made mouth guard. Intralesional steroids
(triamcinolone) have been used effectively in oral and conjunctival lesions. Systemic
steroids are used for severe oral and cutaneous cases or for ocular involvement. A daily
dose of 20 to 60 mg usually provides control and is tapered gradually to keep the disease
under control. A combination of tetracycline 500 mg and niacin 500 mg four times a day
or minocycline alone, 50 to 100 mg daily, can be useful adjuncts to treatment. Steroids in
conjunction with immunosuppressants (azathioprine, cyclophosphamide, methotrexate)
may be needed in advanced cases of recalcitrant disease or in patients with extensive
cutaneous and mucous membrane involvement. Excellent response with prolonged
remission has been obtained with combination of prednisone 1 mg/kg/day and
cyclophosphamide 1 to 2 mg/kg/day. Dapsone alone and in combination with steroids has
been shown to be an effective treatment. Sulfapyridine in combination with steroids also
has been used successfully. Generally, cutaneous lesions respond to treatment better than
mucosal lesions, and oral lesions respond better to treatment than conjunctival lesions
(Table 46.3).
BULLOUS PEMPHIGOID
Etiology
Bullous pemphigus is similar to cicatricial pemphigoid in that antibodies are directed at
the basement membrane, specifically the lamina lucida, resulting in subepithelial bullae.
Clinical Features
The disease most commonly affects persons in their seventh and eighth decades; males
and females are affected equally. The lesions are primarily cutaneous, with particular
affinity for the flexor surfaces of extremities, the inner thighs, the groin, and the trunk.
Oral lesions have been reported in up to 40% of patients; however, oral lesions are rarely
the presenting symptom. Oral lesions, when they occur, cannot be discriminated from
cicatricial pemphigoid, which rarely involves the cutaneous surfaces.
Histopathology
The subepithelial clefting and direct immunofluorescence of bullous pemphigoid are
similar to cicatricial pemphigoid with linear fluorescence of IgG and C3 along the
basement membrane zone. In bullous pemphigoid, however, indirect
immunofluorescence is positive for circulating antibodies in 70% of the cases. These
titers do not correspond to the severity of the disease as they do in pemphigus vulgaris.
Additionally, it was found recently that bullous pemphigoid antibodies bind to an area of
the lamina lucida that is superficial to where the cicatricial pemphigoid antibodies bind.
Differential Diagnosis
The presentation of bullous pemphigoid may be similar to many of the other
vesiculobullous lesions and bears great similarity to cicatricial pemphigoid. As stated
earlier, one hypothesis is that they actually represent slightly different forms of the same
disease. They both affect the elderly, although bullous pemphigoid may affect a slightly
older population. Cicatricial pemphigoid tends to affect twice as many female patients as
male patients, but the sex distribution in bullous pemphigoid is equal. Clinically, bullous
pemphigoid most commonly involves the cutaneous surfaces and much less commonly
the oral mucosa, and cicatricial pemphigoid almost always in-volves the oral mucosa and
rarely the skin. In most cases, both produce positive direct immunofluorescence for IgG
and C3; however, some investigators found that cicatricial antibodies bind to the lamina
lucida deep to the area of the lamina lucida that bullous pemphigoid antibodies bind.
Bullous pemphigoid is positive for indirect immunofluorescence for anti-basement
membrane antibodies in most cases, but cicatricial pemphigoid is only occasionally
positive for the same antibodies in most studies. Indirect immunofluorescence is more
often positive in cicatricial pemphigoid when salt-split skin is used as the control tissue
(Table 46.2).
Treatment
Bullous pemphigoid is often self-limited and may go through periods of clinical
remission; in cicatricial pemphigoid, such a remission is unlikely. Systemic steroids are
usually effective in controlling this problem. Prednisone, starting at 50 to 100 mg/day
(0.6 to 1.2 mg/kg/day) usually will suppress the formation of new blisters. Topical
steroids or intralesional steroids may be effective in controlling localized disease.
Immunosuppressive agents (azathioprine) are used in maintenance therapy, often in
combination with alternate-day steroids, which may also reduce the dose and side effects
of steroids. Other agents, such as sulfapyridine, dapsone, and tetracycline or
erythromycin with niacinamide, also have been used successfully. Recently, high-dose
intravenous gamma globulin has been used successfully when immunosuppressive agents
have failed to provide a steroid-sparing effect. This treatment is expensive and should be
reserved for patients with severe disease requiring high-dose steroids (Table 46.3).
PEMPHIGUS VULGARIS
Etiology
Pemphigus represents a group of mucocutaneous diseases characterized by intraepithelial
(i.e., suprabasilar) vesicle formation. It is an autoimmune disease of unknown etiology
that causes production of autoantibodies against a Ca
2+
-dependent cell adhesion molecule
(i.e., a cadherin) that is involved in the maintenance of epithelial integrity. This results in
the loss of epithelial cell cohesiveness, causing epithelial cell separation (i.e.,
acantholysis), with the formation of intraepithelial blisters. The autoantibodies producing
the intraepithelial disruption are predominately IgG. Activation of the complement
system may enhance the process, but studies show that blister formation can occur
without complement activation (4).
Clinical Features
Most patients are aged 40 to 50 years of age, and there is an equal sex distribution. There
is an increased incidence in Jews and other populations with Mediterranean origins, with
the highest incidence among the Ashkenazic Jews. Most patients develop oral lesions
before cutaneous manifestations. Oral lesions eventually develop in more than 90% of
patients who have skin lesions. Lesions are fragile painful blisters that may occur
anywhere on the oral mucosa or pharynx, but they more commonly occur on the buccal
mucosa, palate, and gingiva (Fig. 46.7; see also Color Plate 8 following p. 370). It is
uncommon to find intact bullae in the mouth; the fluid-filled vesicles rapidly rupture,
producing an ulcer with a gray membrane, which is the usual finding. Gentle scraping or
rubbing of adjacent normal-appearing mucosa strips the mucosa, which is a positive
Nikolsky sign. Also commonly seen is the Asboe-Hansen sign, which is direct pressure
over an intact bullae causing extension of the bullae. Gingival involvement may manifest
as desquamative gingivitis. Cutaneous involvement in pemphigus vulgaris has a
predilection for the face, scalp, axilla, and areas of pressure (i.e., feet, back, hands). The
lesions heal without scarring, but postinflammatory hyperpigmentation may be pres-ent.
Pemphigus vulgaris may occur with other autoimmune diseases, such as rheumatoid
arthritis, Sjgren syndrome, lupus erythematosus, Hashimoto thyroiditis, Graves disease,
myasthenia gravis, and thymoma. It also has been associated with internal malignancies,
referred to by some as paraneoplastic pemphigus (5). Pemphigus also has been induced
by drugs, classically penicillamine, but other drugs, such as captopril, penicillin,
interferon-, and interleukin-2, also have been implicated.

FIGURE 46.7. Pemphigus vulgaris, resulting in severe
desquamation of the palatal (A) and buccal (B) mucosa.
(See also Color Plate 8 following p. 370.)



Histopathology
Dissolution of the intracellular attachments creates an intraepithelial split. The basal cell
layer usually remains attached to the underlying lamina propria, reverting to a cuboidal
shape, producing the so-called row of tombstones (Fig. 46.8). Acantholytic lesions are
pathognomonic for pemphigus vulgaris; they feature free squamous epithelial cells lying
free within the bullae. These free squamous cells assume a more spheric form (i.e.,
Tzanck cells). These cells are also pathognomonic for pemphigus vulgaris. On biopsy the
bullae reveal an inflammatory infiltrate consisting mostly of neutrophils. Direct
immunofluorescence reveals antibodies (usually IgG) directed against desmoglein 3, a
member of the cadherin family (6). The intercellular fluorescence pattern is homogeneous
in lesional and perilesional skin. The pattern is strongest at the parabasilar region, and its
intensity decreases at it approaches the surface. C3, and less commonly IgA and IgM,
also may be deposited in this same pattern. Indirect immunofluorescence is used to
measure the patient's circulating serum antibodies. The titer is associated with the
severity of the disease, and this may be useful in adjusting the therapeutic regimens.
Indirect immunofluorescence is positive in up to 90% of patients; however, circulating
antibodies may be difficult to detect during early phases in patients with lesions limited to
the oral mucosa (5). Recently, genetic studies revealed an increased incidence in persons
with certain class II major histocompatibility complex genes, especially human leukocyte
antigen (HLA) locus DRw4 and DRw6 (4).

FIGURE 46.8. Suprabasilar clefting of pemphigus
vulgaris with the basal cell layer remaining attached to
the lamina propria.



Treatment
Corticosteroid treatment has greatly reduced the mortality and morbidity of this disease;
however, high doses of steroids, often required over a long duration, can produce many
side effects. It has been reported that an 8% to 10% steroid mortality rate exists for these
patients because of the high doses often required. Therefore, it is important to reduce the
steroid to as low a maintenance level as possible. Initially, 60 to 120 mg/day of
prednisone or prednisolone may be required to achieve control of severe disease, with
titration of the dose based on clinical response.
Once control is achieved, the dose is adjusted to heal 80% of lesions. This consolidation
phase of therapy lasts 1 to 4 weeks. After consolidation, patients are withdrawn from
corticosteroids at a rate of 50% every 2 weeks. Alternate-day therapy can be initiated
when the dose is reduced below 80 mg/day while continuing to reduce the average daily
dose by the same amount. For the 2 to 3 weeks before ceasing therapy, the dose is held at
5 mg every other day (6). More refractory patients usually are treated with prednisone
and immunosuppressive agents, such as azathioprine 50 mg/day with weekly increments
of 50 mg/day, cyclophosphamide 50 to 150 mg/day, and cyclosporine 5 mg/kg/day
(cyclosporine is reported to have a much more rapid effect than azathioprine). Occasional
cases of pemphigus vulgaris will respond well to dapsone, either alone or as an adjuvant
to corticosteroid therapy. Intramuscular gold, with or without corticosteroids, has been
used successfully; however, it also can produce serious side effects, such as bone marrow
suppression and renal toxicity. Tetracycline 500 mg and niacinamide 500 mg three times
daily have been used successfully. Plasmapheresis, in combination with agents to
suppress rebound increased antibody production (i.e., immunosuppressive agents), has
been used successfully in treatment of therapy-resistant cases of pemphigus vulgaris.
Photophoresis and photochemotherapy have been used effectively in pemphigus vulgaris.
The use of gamma globulin and proteinase inhibitors in pemphigus are being investigated
(6) (Table 46.3).
ERYTHEMA MULTIFORME
Etiology
Erythema multiforme is an inflammatory eruption characterized by symmetric
erythematous, edematous, or bullous lesions of the skin and mucous membranes.
Although the mechanism causing erythema multiforme is unknown, a hypersensitivity
reaction has been implicated. Deposition of antigen-antibody complex in the small
vessels of the dermis or submucosa has been implicated; however, the histopathology
does not show the vascular damage typical of this type of immunopathology.
Furthermore, autoantibodies have not been found in patients with erythema multiforme.
The most common cause of erythema multiforme has been from secondary HSV (types I
and II) infection, accounting for more than half of all cases. HSV is associated with
nearly 100% of cases of recurrent erythema multiforme; however, histology of erythema
multiforme is not consistent with an active HSV infection, and viral cultures are typically
negative. Immunofluorescence has been shown to be positive for HSV-specific antigens
in epidermis of affected patients. Because autoantibodies are not found in these patients,
these findings suggest that the pathogenesis may be HSV-specific cell-mediated
immunity. Other infectious triggers have been implicated, including tuberculosis,
bacterial, and fungal infections. Multiple medications also have been implicated,
including barbiturates and sulfonamides. Other factors are malignancy, vaccines,
radiation therapy, autoimmune hypersensitivity, and stress.
Clinical Features
The disease is usually a self-limited process that most commonly afflicts young adults.
Onset is usually explosive, involving the skin, mucous membranes, or both, although
both persistent and recurrent forms of the disease have been described. The persistent
form of the disease is rare and presents with uninterrupted occurrence of typical and
atypical lesions (7). Prodromal symptoms of itching and burning are often present,
especially in areas where lesions ultimately develop. In most cases, recurrent herpes
labialis precedes the development of erythema multiforme by about 10 days. The
cutaneous lesions are characterized as rap-idly evolving symmetric eruptions of
erythematous macules, papules, vesicles, bullae, or urticarial plaques over the hands, feet,
arms, legs, face, and neck. Target lesions (i.e., iris lesions) consisting of concentric
erythematous rings separated by rings of near-normal color are considered
pathognomonic. Oral lesions occur in 25% to 50% of the patients with cutaneous lesions.
They may occur anywhere orally, but the lips, buccal mucosa, palate, and the tongue are
most commonly involved. The lips may become encrusted, and the entire perimeter of the
tongue is usually involved. Signs and symptoms range from mild discomfort to severe
pain, headache, and lymphadenopathy.
Stevens-Johnson Syndrome
Stevens-Johnson syndrome is a severe form of erythema multiforme; lesions affect the
mouth, eyes, skin, genitalia, and occasionally the esophagus and respiratory tract. They
are often accompanied by high fever, malaise, and photophobia. Ocular inflammation
(i.e., conjunctivitis, uveitis) can lead to blindness. Stevens-Johnson syndrome does not
appear to be closely associated with HSV, as is erythema multiforme; rather, most cases
appear to be drug induced.
Toxic Epidermal Necrolysis
Toxic epidermal necrolysis is also a severe form of erythema multiforme with painful
cutaneous and mucous membrane lesions. Oral lesions are the most common site of
mucous membrane involvement and may extend back to the pharynx. The hallmark of
toxic epidermal necrolysis is widespread detachment of the full thickness of the
epidermis with total or partial necrosis. Most, if not all, cases are thought to be drug
induced. More than 80% of all cases can be linked to a specific drug. The most common
drugs involved include sulfonamides, barbiturates, phenytoin, and allopurinol (8).
Histopathology
Erythema multiforme is generally considered to have no specific histologic appearance.
HSV-associated lesions show hydropic degeneration along the basal cell layer,
keratinocyte necrosis, and a mononuclear cell infiltrate. The vesicle of erythema
multiforme usually is considered to be subepithelial, occurring at the interface of
epithelial and connective tissue, but intraepithelial vesicles also have been described. A
perivascular infiltrate of lymphocytes and macrophages appears with edema in the lamina
propria or papillary dermis. Direct and indirect immunofluorescence are nonspecific for
erythema multiforme.
Differential Diagnosis
Erythema multiforme must be differentiated from other vesiculobullous diseases, such as
cicatricial pemphigoid, pemphigus vulgaris, herpetic stomatitis, and erosive lichen
planus. Al-though the histopathologic features of erythema multiforme are nonspecific,
biopsies and immunofluorescence are useful for ruling out these other entities. Erythema
multiforme presents with an explosive presentation, often after recurrent herpes labialis,
other infectious causes, or exposure to certain medications. Erythema multiforme can be
differentiated from primary herpes by its relative lack of vesicles, location on the
unattached tissues intraorally (e.g., lips, buccal mucosa, palate, tongue), and cytologic
findings with early herpetic lesions. Aphthous ulcers usually can be differentiated by
their unique history and clinical presentation.
Treatment
Mild cases may be treated with supportive care (e.g., fluids and analgesics) and
antibiotics for secondary bacterial infections. The disease usually runs its course within 2
to 3 weeks and then subsides. Topical application of steroids (e.g., fluocinonide,
betamethasone) may be required for mild to moderate cases. Severe cases (i.e., Stevens-
Johnson syndrome, toxic epidermal necrolysis) should be treated with systemic steroids.
A short course of 40 to 80 mg daily of prednisone, followed by a tapered dose over
several weeks, is usually successful in controlling the disease. Recurrent erythema
multiforme may require intermittent steroid use; however, systemic steroid therapy could
lower the patient's resistance to HSV, which could precipitate recurrent herpes, followed
by another bout of erythema multiforme. When patients with recurrent erythema
multiforme are given acyclovir 600 to 800 mg/day to prevent recurrent herpes labialis,
erythema multiforme seems to be prevented. Patients with multiple recurrences may be
controlled with high doses of tetracycline and niacinamide.
LICHEN PLANUS
Etiology
Lichen planus is an inflammatory disease in which the basal cell layer is destroyed by
activated lymphocytes. The cell-mediated immune process activates lymphocytes that
become cytotoxic for basal keratinocytes.
Clinical Features
Lichen planus affects women more often than men, and 80% of the patients are over 40
years of age. Children are rarely affected. The prevalence in the general population has
been estimated at 0.02% to 2%. The skin lesions appear as small violaceous pruritic
papules over the flexor surfaces of the extremities and do not last as long as oral lesions.
Sixty percent to 70% of patients with skin lesions have oral lesions, which may appear
without any cutaneous lesions. Cutaneous lesions occur in 20% to 60% of patients with
oral lichen planus. Several types of lichen planus in the oral cavity have been described:
reticular, plaque, atrophic, erosive, and bullous. The reticular form has interlacing white
keratotic striae (Wickham striae), producing an annular or reticular pattern (Fig. 46.9; see
also Color Plate 9 following p. 370). The buccal mucosa most commonly is affected, but
the tongue, gingiva, or lips also may be involved. The reticular form is the most common
and is usually asymptomatic or has minimal symptoms. The plaque form resembles
leukoplakia and is found on the dorsum of the tongue and the buccal mucosa. The plaque
form is also usually asymptomatic. The atrophic form may be seen with the reticular or
erosive forms and frequently involves the attached gingiva, producing desquamative
gingivitis. The atrophic form typically is accompanied by pain or burning. The erosive
form has a changing pattern of involvement, with an erythematous erosion covered with a
fibrinous layer. Erosive lichen planus is typically very painful (Fig. 46.10; see also Color
Plate 10 following p. 370). The bullous form is rare and may range from a few
millimeters to several centimeters. The bullae rapidly rupture, leaving a raw, painful,
ulcerated bed. The lesions most commonly affect the buccal mucosa and the lateral
border of the tongue. The clinical course is usually long, with numerous remissions and
exacerbations. Emotional stress may precede the oral manifestations of the disease.

FIGURE 46.9. Asymptomatic interlacing white keratotic
striae (Wickham striae) of reticular lichen planus. (See
also Color Plate 9 following p. 370.)



FIGURE 46.10. Painful erosive lichen planus of the
palate. (See also Color Plate 10 following p. 370.)



Oral lichen planus, especially the erosive and atrophic forms, are believed to have a
slightly higher risk of malignant degen-eration than cutaneous lesions. Controversy
continues over whether oral lichen planus is a precancerous condition. The rate of
malignant transformation has been estimated at 1% to 5%, which is a greater than 20-fold
increase over the general population (9). It is not known whether erosive lichen planus
actually undergoes malignant transformation or whether the lesions may be more
predisposed to malignant transformation by carcinogens.
A new entity, lichenoid dysplasia, was introduced in 1985 to describe dysplastic lesions
that had been erroneously described in the literature as lichen planus. Lichenoid dysplasia
is considered to be a precancerous condition (9).
Histopathology
Microscopically, lichen planus appears as hyperkeratosis (e.g., hyperparakeratosis,
hyperorthokeratosis), liquefactive degeneration of the basal cell layer, a saw-toothed
rete peg formation, and a bandlike lymphocytic infiltration immediately below the
epithelium in the lamina propria parallel to the epithelial surface. Additionally, variable
degrees of acantholysis can be seen (Fig. 46.11). Discrete eosinophilic ovoid bodies (i.e.,
necrotic keratinocytes) called civatte bodies occasionally are observed in the basal cell
layer. Civatte bodies are considered suggestive of but not pathognomonic for the disease.
Direct immunofluorescence detects fibrinogen along the basement membrane zone in
90% to 100% of cases. Although less common, assays for complement and
immunoglobulins also may be positive. These findings are of limited value because they
are not specific for lichen planus; they also are found in lupus erythematosus and
erythema multiforme. Indirect immunofluorescence provides no further diagnostic
information. Recent immunohistochemical and two-dimensional gel electrophoresis
studies showed alterations in the normal pattern of cytokeratin expression in oral lichen
planus. In particular, cytokeratin 19 is increased in oral lichen planus and is thought
possibly to be a marker of transformation in precancerous lesions.

FIGURE 46.11. Histologic view of lichen planus with
liquefactive degeneration of the basal cell layer and
bandlike lymphocytic infiltration of the lamina propria.



Differential Diagnosis
The reticular or plaque forms of lichen planus must be differentiated from other white
lesions, such as atrophic candidiasis, DLE, and lichenoid dysplasia. Biopsy is usually
sufficient. Erosive and atrophic lichen planus must be differentiated from other
vesiculobullous lesions that may present as desquamative gingivitis, such as pemphigus
vulgaris, cicatricial pemphigoid, bullous pemphigoid, and erythema multiforme. The
distinctive histologic features of lichen planus are usually sufficient to make the
appropriate diagnosis (Table 46.2).
Treatment
Improvement of the signs and symptoms of atrophic and ulcerative gingival lichen planus
may occur with improvement of oral hygiene with tooth brushing, toothpicks, flossing,
and 0.02% chlorhexidine rinses. More severe or symptomatic cases usually are treated
with agents that modify the immune system. Topical steroids or injections may be useful
in controlling the disease locally. Cyclosporine, 500 mg/day for 4 to 8 weeks, in the form
of mouth rinse has been shown to improve healing of lesions significantly and reduce
pain (10). Systemic steroids are generally reserved for the painful erosive variety (11).
Systemic and topical retinoids have been used for reticular and plaque forms. The
retinoids are believed to have antikeratinizing and immunomodulating functions.
Dapsone has been used to control the severe forms of lichen planus. Local long-wave
ultraviolet light exposure of oral lichen planus lesions in patients pretreated with
psoralens has also proved effective. However, for cutaneous lesions, this treatment has
shown a significant dose-dependent increased risk of squamous cell cancer of the skin
(Table 46.3).
CANDIDIASIS
Etiology
Mucositis and pharyngitis are commonly due to fungal infections. Candidiasis is a term
applied to infection secondary to the Candida fungal genus. Candida species are
commonly present in the normal oral flora in 40% to 60% of the normal population.
Genus Candida has about 150 different fungal species, seven of which (C. albicans, C.
tropicalis, C. parapsilosis, C. krusei, C. keyyr, C. glabrata, and C. guilliermondii) are
important pathogens. C. albicans is the most common fungal species isolated from the
human body as either a commensal or as an opportunistic pathogen (12). The relationship
between the commensal state and that of pathogenicity may be difficult to interpret.
Many local and systemic factors may predispose a person to candidal infections. Local
factors, such as physical irritation, preexisting infection, nutritional deficits, poor oral
hygiene, denture wearing, smoking, and individual sensitivity, can lead to mucosal
breakdown and loss of the epithelial barrier. This tissue breakdown may expose
extracellular matrix proteins (e.g., laminin, collagen, fibronectin), to which Candida ex-
presses adhesions, thus facilitating adhesion that is essential to colonization. Systemic
predisposing factors include endocrine alterations (e.g., diabetes, pregnancy,
hypoadrenalism), AIDS, malignancy (especially leukemia and lymphoma), systemic
broad-spectrum antibiotic therapy, systemic and inhaled steroid therapy, immature
immunologic states of infancy, radiation or chemotherapy, altered phagocytosis,
pregnancy, and old age. The tissue damage seen secondary to candidiasis is mostly the
result of the host inflammatory response.
Clinical Presentation
The oral presentation of candidiasis varies, and several clinical varieties have been
described. Pseudomembranous candidiasis (i.e., thrush) is the classic form. It presents as
adherent, white, confluent, soft plaques that can be wiped off the epithelial surface with
gauze or a cotton applicator, leaving an eroded or ulcerated erythematous surface that is
tender (Fig. 46.12; see also Color Plate 11 following p. 370). The plaques are com-posed
of fungal organisms, keratotic debris, inflammatory cells, desquamated epithelial cells,
bacteria, and fibrin. Although thrush may appear anywhere in the oral cavity, the buccal
mucosa, mucobuccal folds, oropharynx, and lateral aspects of the dorsal tongue are the
most commonly involved. This clinical infection is seldom painful, but severe cases with
erosion of the mucosa can produce a burning sensation. Direct spread to the pharynx,
larynx, and esophagus may lead to dysphagia. Thrush is found in neonates (5%),
debilitated elderly patients (10% to 15%), patients undergoing chemotherapy and
radiation therapy (5%), and HIV-seropositive patients (12).

FIGURE 46.12. Soft white plaques of
pseudomembranous candidiasis (thrush). (Courtesy of Dr.
Robert O. Greer.) (See also Color Plate 11 following p.
370.)



Acute atrophic candidiasis presents as an erythematous patch or as a diffuse erythematous
lesion. Patches of depapillation and dekeratinization may occur along the dorsum of the
tongue, resulting in a red, edematous, painful tongue. Because it may follow acute
pseudomembranous candidiasis or follow the administration of antibiotics, it has been
called antibiotic sto-matitis or antibiotic glossitis. The single use of broad-spectrum or
multiple use of narrow-spectrum antibiotics may produce this candidal infection. Acute
atrophic candidiasis usually produces oral symptoms of burning or pain. Diagnosis can be
made by smear and culture. Improvement usually follows the withdrawal of the inciting
antibiotic(s) and initiation of good oral hygiene. Antifungals in the form of gels, oral
suspensions, or pastilles are usually better tolerated than tablets because of the underlying
discomfort. Chronic atrophic candidiasis (formerly called denture candidiasis) is the most
common form of oral candidiasis, found in up to 60% of denture-wearing patients. It is
caused by chronic low-grade trauma from poor-fitting partial or full dentures. Poor
occlusion and failure to remove dentures at night are also predisposing factors. It presents
as a diffuse erythema with a pebbly to velvety surface and is limited exclusively to the
denture-bearing mucosa, sometimes mixed with pseudomembranous areas. Angular
cheilitis is another form of chronic atrophic candidiasis that may be related to poor
denture construction. If the vertical dimension of the dentures is less than ideal,
overclosure may result in prominent folds at the commissures (Fig. 46.13; see also Color
Plate 12 following p. 370). Salivary accumulation in these folds encourages candida
colonization, and the folds become moderately painful, eroded, or macerated. This may
also be seen in dentulous patients who habitually lick their lips.

FIGURE 46.13. Angular cheilitis. Candidal colonization
of the oral commissures led to moderately painful
macerated folds. (See also Color Plate 12 following p.
370.)



Hyperplastic candidiasis, or candidal leukoplakia, is a hyperplastic response to chronic
candidal infection. It resembles leukoplakia in that it cannot be rubbed off with a gauze or
cotton swab. The lesions are most commonly found on the buccal mucosa but also may
be seen on the palate or tongue. This condition also may occur immediately posterior to
the commissural fold and retrocommissural folds, especially in smokers. This form of
candidiasis has a significant increase in epithelial atypia and malignant transformation.
Median rhomboid glossitis, once thought to be secondary to a developmental
abnormality, is now thought to be a variant of candidiasis. The lesion appears as an
asymptomatic diamond-shaped area of depapillation found anterior to the circumvallate
papillae.
Mucocutaneous candidiasis also has several forms. The local variety is confined to the
oral mucosa, skin, nails, and vaginal mucosa. It may show up early in life and is often
resistant to standard therapies, which may secure only a temporary remission. This form
usually manifests as a pseudomembranous candidiasis that evolves with nail and skin
involvement. About 20% of the mucocutaneous patients represent a familial form of
candidiasis. Transmission is considered to be autosomal recessive. About half of the
familial cases also express an endocrinopathy, which may include hypothyroidism,
Addison disease, or diabetes mellitus.
Histopathology
A cytologic smear can identify Candida. Plaque removed from the epithelial surface in
the pseudomembranous form can be smeared on a microscope slide, stained with 20%
KOH, and evaluated for the presence of hyphae. Because fungal cultures can be isolated
from 40% of the normal dentulous population, they are of little use. Pseudomembranous
lesions show a localized superficial inflammatory reaction with erosion or ulceration of
the epithelial surface. In most cases, fungal cells invade the stratum corneum but do not
invade beyond the stratum spi-nosum, and subepithelial infections with Candida are
considered an ominous indicator of immune deficiency (12).
Yeast hyphae with fibrin and inflammation are found in large numbers. Periodic acid-
Schiff or methenamine silver may en-hance the fungi within the specimen. Epithelial
hyperplasia is commonly associated with the chronic varieties.
Treatment
Topical or systemic antifungals may be used for the treatment of candidiasis. Topical
agents are available as oral rinses, oral or vaginal tablets, and creams. The tablets are
dissolved slowly in the mouth and therefore have the advantage over oral rinses of
prolonged contact with the infected site. The vaginal tablets usually dissolve a little more
slowly than the oral tablets. Patients with dry mouth may have difficulty dissolving the
tablets, producing mucosal irritations of friable mucosa. Oral rinses may provide
antifungal coverage in these patients, even though they allow less medicinal contact time
with the lesion. The creams are useful for application to the corners of the mouth or
placed in dentures to provide prolonged contact to the palatal mucosa during denture use.
If topical agents fail, systemic agents are used to control the infection. Although oral
treatment may be effective, intravenous antifungals are usually required for systemic
candidiasis in immunosuppressed patients.
Nystatin and amphotericin B are membrane-active fungicidal antibiotics from the
Streptomyces species (12). Nystatin is a topical medication for oral and pharyngeal
candidiasis. It is available as oral and vaginal tablets, lozenges, suspension rinse, and
cream. For therapeutic effects, nystatin should be given five times each day for at least 2
weeks in the nonimmunocompromised host to allow a shift in the oral flora. A shorter
treatment regimen may result in reinfection. Therapy may be continued 2 to 3 weeks after
resolution of signs and symptoms in difficult cases. Amphotericin B is a toxic drug that
can be administered intravenously or orally. Orally, it is not absorbed, and actions are
limited to the intestines. Intravenous administration may produce fever, chills, myalgia,
and nausea. Amphotericin B also causes serious side effects, including nephrotoxicity,
bone marrow toxicity, and cardiovascular toxicity. Amphotericin B may be given with
flucytosine for synergistic effects.
Flucytosine is a fluorinated pyrimidine that acts by inhibition of thymidylate synthase,
interrupting fungal DNA synthesis. Because resistance may become a problem if it is
used as a single agent, flucytosine is often used in combination therapy with amphotericin
B. Toxic effects include leukopenia or thrombocytopenia, elevation of hepatic enzymes,
nausea, and vomiting. Although flucytosine is not nephrotoxic, it is eliminated through
the kidneys, and levels should be monitored closely in patients with renal dysfunction.
Additionally, it potentiates the nephrotoxicity of amphotericin B. The usual dose is 50 to
150 mg/kg orally four times daily.
The imidazoles (e.g., ketoconazole, clotrimazole, miconazole) are synthetic fungistatics
or fungicidals, depending on the dose, that inhibit the synthesis of ergosterol, which alters
membrane permeability and interferes with purine transport. Ketoconazole has become
the drug of choice for chronic mucocutaneous candidiasis and esophagitis. Ketoconazole
is often used in HIV patients and prophylactically in neutropenic patients. The usual
dosage of ketoconazole is 200 mg/day orally and 400 mg/day orally for patients who do
not respond to the lower dose. It depends on gastric acidity for absorption, and patients
receiving antacids, H2 blockers, or other medications affecting gastric secretion should
receive these medications 2 hours after ketoconazole administration. Side effects include
nausea, vomiting, abdominal pain, pruritus, headache, dizziness, hepatotoxicity,
somnolence, gynecomastia, and impotence; it has been shown to be teratogenic in
animals.
Clotrimazole is the most potent topical imidazole antifungal. It is indicated in
oropharyngeal candidiasis and is administered orally as 10-mg lozenges (troches) given
five times a day. It is also available in topical solutions, in cream form, and as vaginal
tablets. Adverse reactions include abnormal liver function, nausea, vomiting, pruritus,
and urticaria.
Fluconazole is a synthetic triazole antifungal agent that may be used for oropharyngeal,
esophageal, or systemic candidiasis. Side effects include nausea, vomiting, headache,
urticaria, abdominal pain, diarrhea, thrombocytopenia, and hypokalemia. Because the
oral absorption is extremely rapid, the oral and intravenous daily doses are equal. The
usual oropharyngeal or esophageal dose is 200 mg orally or intravenous on the first day,
followed by 100 mg daily for at least 14 days after resolution of the symptoms. Doses of
up to 400 mg daily may be used, depending on the patient's response to therapy. Systemic
candidiasis is treated with 400 mg on the first day, followed by 200 mg daily for at least 2
weeks after resolution of symptoms. Fluconazole is primarily excreted unchanged in the
urine, and therefore the administered dose must be adjusted for patients with renal
impairment.
Chlorhexidine gluconate (0.1%) is a topical agent with microbicidal characteristics. Ten
milliliters used as a mouth rinse three to four times each day may be helpful in
oropharyngeal candidiasis. Dentures can be soaked in chlorhexidine or a hypochlorite
solution overnight for chronic atrophic candidiasis (Table 46.3).
RECURRENT APHTHOUS STOMATITIS
Etiology
Aphthous ulcers are the most common type of nontraumatic ulcer. The incidence ranges
from 10% to 20% in the general population and as high as 50% in selected groups
(13,14). Prevalence tends to be more common in upper socioeconomic groups and
professional persons. The cause is unknown, but several agents have been implicated:
viral (e.g., HSV, cytomegalovirus, VZV, Epstein Barr virus) infections, bacterial (e.g.,
Streptococcus sanguis) infections, nutritional deficiencies (e.g., vitamin B
12
, folic acid,
iron), hormonal alterations, stress, trauma, food allergies (e.g., nuts, chocolate, glutens),
and immunologic abnormalities. The best evidence points to an immunologic mechanism.
Autoantibodies to oral mucosal membranes have been found that react to the prickle cell
layer rather than the basal cell layer as would be expected; however, these antibodies
cross-react with other tissues where aphthous ulcers are not found. The autoimmune
response has also been associated with an antibody response to the tissue's muco-
polysaccharide encapsulation of the L form of -hemolytic Streptococcus. There may
also be a defect in cell-mediated immunity, evidenced by an increased number of helper
T cells, a decreased number of suppressor T cells, and basal cells displaying HLA-DR
antigens that are required for antigen presentation to helper T cells. Additionally, T cells
from affected patients have been shown to be cytotoxic to cultured gingival epithelia but
not to other epithelia. A recent study supported the possibility of aphthous ulcers being
related to reactivation of VZV or cytomegalovirus. It was found that most patients with
recent aphthous ulcers had elevated IgM titers to VZV or cyto-megalovirus, which was
not observed in the control group.
Clinical Features
There are three basic manifestations: minor aphthous ulcers, major aphthous ulcers, and
herpetiform ulcers. It is believed that they have a common cause and are different forms
of the same disease.
Minor aphthous ulcers usually measure less than 1.0 cm and are located on the
keratinized freely movable gingiva. The lesions appear as well-delineated white ulcers
with erythematous halos (Fig. 46.14; see also Color Plate 13 following p. 370). They
usually last 7 to 10 days without scarring. The lesions often are heralded by a tingling or
burning sensation before development of ulcers. Recurrence is variable, and long lesion-
free periods are common. Treatment is often necessary to abate the pain, which appears
greater than expected for this lesion.

FIGURE 46.14. Recurrent aphthous stomatitis. A minor
aphthous ulcer with a central white ulceration is
surrounded by an erythematous halo on the buccal
mucosa. (See also Color Plate 13 following p. 370.)



Major aphthous ulcers have been known as Sutton disease or periadenitis mucosa
necrotica recurrens. The lesions are much less common than minor aphthae but much
more severe. They range from 1 to 3 cm in diameter and may persist from 6 weeks to
several months. In contrast to minor aphthae, they heal by scarring. Major aphthous
ulcers also involve the keratinized movable mucosa and frequently involve the tongue,
palate, and anterior faucial pillar. The lesions are often multiple, with new ulcer
formation beginning as an older lesion heals.
Herpetiform ulcers represent an extremely painful crop of 20 to 200 small ulcers that are
1 to 3 mm in diameter. These ulcers may occur on movable and attached gingiva or on
the tongue and palate. Healing occurs in 1 to 2 weeks. Although they appear similar to
herpetic lesions, they differ from them in that they lack a vesicular stage. Herpetiform
ulcers are not caused by HSV; no herpes virus can be cultured from the lesion, and
antibodies to HSV in the oral mucosa cannot be identified.
Histopathology
There are no microscopic features diagnostic of aphthous ulcers. Mononuclear cells,
predominantly helper T cells, often are found in the submucosa before the ulcerative
stage. Mac-rophages and mast cells are commonly found in the ulcer base. Extravasated
red blood cells and neutrophils are often present in the early stages of lesions. No virus
has been cultured from infected cells.
Differential Diagnosis
Aphthous ulcers can be differentiated from herpetic lesions clinically. The aphthous
ulcers usually occur on the free keratinized tissue and are not preceded by vesicles;
herpetic lesions are preceded by vesicles on firmly attached gingival and palatal tissue.
Traumatic ulcers have a history of preceding trauma, and vesiculobullous lesions have a
different clinical picture and unique histology and immunofluorescent findings (Table
46.2).
Treatment
Many different treatments have been used for aphthous ulcers, ranging from chemical or
electrocautery to medical therapy. Medical treatment has included the use of antibiotics;
antiinflammatories; immunosuppressants; and the oral intake of yogurt, cultured
buttermilk, and lactobacillus capsules. An oral suspension (200 mg per 5 mL) of
tetracycline taken every 6 hours for 5 to 7 days has been used with good results.
Chlorhexidine 0.12% rinse also has been used with some success. Topical steroid
ointments such as 0.05% fluocinonide (Lidex) or topical steroid rinses with
betamethasone (Celestone) may shorten the duration significantly, especially if used
during the prodromal stage of the minor aphthae. Because topical steroids augment the
overgrowth of C. albicans, it is recommended that an antifungal should be used in
conjunction with the topical steroid. Orabase may be used as a steroid carrier for
application to the oral mucosa. An equal mixture of 15 g of Orabase and 15 g of 0.05%
fluocinonide may be applied to the lesions 6 to 8 times each day. Systemic steroids are
reserved for the severe aphthae. Twenty to 40 mg of prednisone daily for 1 week
followed by another week at half the initial dose may be needed to control major aphthae.
Other antiinflammatory agents, such as sulfones and sulfonamides, that work by altering
neutrophil function, may be useful. Retinoids have been used empirically, but clinical
testing has not been done. Zilactin is a medicated gel that produces a protective film over
the ulcer for several hours. Sucralfate suspension, when taken orally, forms a pastelike
coating that attaches ionically to damaged mucosa and has been shown to reduce pain and
healing time and to increase the remission time. Immunosuppressants (e.g., azathioprine)
also have been used effectively for major aphthae. Colchicine 1.5 mg/day has been found
to prevent or significantly reduce the severity of all types of recurrent aphthous ulcers.
How colchicine exerts its effect is not known; however, it is known that colchicine
inhibits neutrophil recruitment, which may be its mechanism of action. Prostaglandins are
biologically active lipids produced by the body that have multiple effects, including
modulation of the inflammatory response. Prostaglandin E
2
recently was used
successfully as a prophylactic agent for recurrent aphthous ulcers (Table 46.3).
MUCOSITIS
Etiology
Mucositis may develop in patients receiving chemotherapy, radiation therapy, or
immunosuppression for bone marrow transplantation. The changes in the oral mucosa
may present as generalized erythema or progress to large ulcers with or without
hemorrhage. The mucosa initially becomes reddened and swollen, followed by
ulceration, which may become covered with a fibrinous exudate (Fig. 46.15; see also
Color Plate 14 following p. 370). Pain or a burning sensation is often present during rest
and is greatly exacerbated by hot or spicy foods. This condition can result in pain,
decreased food intake, systemic or local infections, and an interruption in the needed
therapy. The onset and intensity depend on the fractionation and duration of radiation
therapy, location of the lesion, and degree of oral hygiene. Radiation-induced mucositis
often appears by the second week of therapy and may persist for 2 to 3 weeks after
completion of radiation therapy (15).

FIGURE 46.15. Erythematous and ulcerative changes of
oral epithelium secondary to radiation-induced mucositis.
(Courtesy of Dr. Robert O. Greer.) (See also Color Plate
14 following p. 370.)



Once mucositis has occurred, treatment is mostly to palliate symptoms. The National
Cancer Institute recommends several components of care, including cleansing of the oral
mucosa, maintenance of moisture, and the relief of pain and inflammation. Hydrogen
peroxide and water (4:1 solution) and saline and sodium bicarbonate solutions have been
advocated to enhance cleansing of the oral mucosa. A soft toothbrush, toothettes, and
unwaxed dental floss also should be used as part of this regimen. Lemon glycerine swabs
have been ineffective for cleansing the oral mucosa.
K-Y jelly, petroleum jelly, and mineral oil have been used to keep the lips clean, moist,
and intact. Numerous anesthetic or analgesic mucosal coating agents have been used to
provide symptomatic relief. Many of the mixtures have included combinations of
diphenhydramine (Benadryl), attapulgite (Kaopectate), milk of magnesia, viscous
lidocaine, Orabase, and dyclonine hydrochloride (Dyclone). Routine oral care (e.g., soft
toothbrush, fluoride toothpaste, dental floss, and lip lubricant) should be done four times
a day. For mild stomatitis, a bland diet can be combined with oral hygiene care as often
as every 2 hours. Mucosal coating agents (e.g., anesthetics, analgesics) also may be
required because mucositis worsens during radiation treatments.
Although no prophylactic protocol has proved 100% effective in preventing mucositis
after chemoradiotherapy and immunosuppression before bone marrow transplantation,
some have shown promise. Prostaglandin E
2
is an endogenously produced cytoprotectant
that some studies have shown reduces the occurrence and severity of mucositis.
Sucralfate is an aluminum salt of sucrose sulfate that forms an ionic bond with proteins
found in the ulcer site, creating a protective barrier. It is of some benefit as a prophylactic
agent for mucositis. Painting the oral mucosal surface with 2% silver nitrate solution
three times daily for 5 days before radiotherapy has been used successfully to decrease
the severity and duration of mucositis. Pretreatment with pentoxifylline decreases the
production of tumor necrosis factor, which decreases the inflammatory response. This
pretreatment also has been used with some success to decrease the severity of mucositis.
Azelastine hydrochloride is an antioxidant that has been an effective prophylactic agent
when administered at 2 mg/day. Chlorhexidine 0.12% rinses three times a day have been
shown in some studies to be a successful prophylactic agent, whereas other studies have
shown no benefit. Benzyd-amine, an NSAID/antimicrobial drug used as a 0.15% rinse six
times a day, can delay the onset and reduce the severity of mucositis. A 30-minute oral
rinse with ice chips (oral cryotherapy) before chemotherapy also can reduce the severity
of mucositis.
ACQUIRED IMMUNODEFICIENCY SYNDROME
AIDS-related diseases caused by the HIV infection have many oral manifestations, some
of which were discussed earlier in this chapter. Many of the oral manifestations are the
results of opportunistic infections. It is important that the otolaryngologist-head and neck
surgeon is familiar with the oral manifestations associated with HIV and AIDS so that
proper treatment can be initiated and the patient can be referred to an infectious disease
specialist for treatment of the systemic disease (see Chapter 21).

HIGHLIGHTS
Primary herpetic gingivostomatitis generally affects children
with crops of small vesicles, which quickly rupture into ulcers
and heal in 7 to 14 days without scarring. Recurrent herpes
(herpes labialis) often is precipitated by trigger factors resulting
in ulcers at the mucocutaneous junction of the lips.
Herpes zoster is the reactivation of the VZV causing
chickenpox. Zoster travels along dermatomes and most
commonly affects the ophthalmic branch of the trigeminal
nerve.
The three major clinical manifestations of lupus erythematosis
(i.e., DLE, SCLE, SLE) may have similar oral presentations,
but SLE affects the visceral organs with increased morbidity
and mortality. Renal involvement may lead to
glomerulonephritis, the most common cause of death in the
SLE patient.
Cicatricial pemphigoid most commonly afflicts the
oropharyngeal mucosa, followed by the conjunctiva, and
infrequently the cutaneous surfaces. Direct
immunofluorescence is strongly positive for the basement
membrane; however, indirect immunofluorescence is usually
negative. Involvement of the conjunctiva or oropharyngeal-
laryngeal mucosa can lead to blindness or great problems with
deglutition and respiration.
Bullous pemphigoid is primarily a cutaneous disease that
closely resembles cicatricial pemphigoid when it affects the
oral mucosa. Both direct and indirect immunofluorescence is
usually positive, although titer level does not correspond with
severity of disease.
Pemphigus vulgaris is a mucocutaneous disease with
intraepithelial vesicle formation and often is associated with
other autoimmune diseases (i.e., rheumatoid arthritis, Sjgren
syndrome, lupus erythematosus, Hashimoto thyroiditis, Graves
disease, myasthenia gravis). Direct and indirect
immunofluorescence are positive, with titers corresponding to
severity of disease.
Erythema multiforme has an explosive onset and affects oral
and cutaneous sites, often after a herpetic infection. More
severe forms (Stevens-Johnson syndrome, toxic epidermal
necrolysis) usually are associated with drug reactions and may
require steroid therapy.
Lichen planus has a variety of presentations in the oral cavity
(reticular, plaque, atrophic, erosive bullous). The reticular is the
most common presentation and is usually asymptomatic. The
distinctive histologic features usually allow differentiation from
other mucosal lesions.
Pseudomembranous candidiasis (thrush) is the most common
oral presentation of candidiasis. Other forms include acute
atrophic, chronic atrophic, hyperplastic, and mucocutaneous
candidiasis. Diagnosis may be accomplished by smears or
biopsy, and oral or topical antifungal treatment is usually
successful.
HIV-related oral diseases include fungal (candidiasis,
cryptococcoses, histoplasmosis) infections, viral (herpes,
varicella zoster, human papillomavirus) infections, bacterial
(gingivitis, periodontitis) infections, and neoplastic (Kaposi
sarcoma, non-Hodgkin lymphoma) manifestations.
CHAPTER REFERENCES
1. Gately LE, Nesbitt LT. Update on immunofluorescent testing in bullous diseases and lupus
erythematosus. Dermatol Clin 1994;12:133.
2. Amir J, Harel L, Smetana Z, et al. Tretament of herpes simplex gingivostomatitis with aciclovir in
children: a randomised double blind placebo controlled study. BMJ 1997;314:18001803.
3. Redford TW, Small RE. Update on pharmacotherapy of systemic lupus erythematosus. Am J
Health Syst Pharm 1995;52:2686.
4. Becker BA, Gaspari AA. Pemphigus vulgaris and vegetans. Dermatol Clin 1993;11:429.
5. Thivolet J. Pemphigus: past, present and future. Dermatology 1994;189:26.
6. Huilgol SC, Black MM. Management of the immunobullous disorders, II: pemphigus. Clin Exp
Dermatol 1995;20:283.
7. Drago F, Parodi A, Rebora A. Persistent erythema multiforme: report of two new cases and review
of literature. J Am Acad Dermatol 1995;33:366.
8. Roujeau JC. The spectrum of Stevens-Johnson syndrome and toxic epidermal necrolysis: a clinical
classification. J Invest Dermatol 1994;102:28s.
9. Cleary KR, Batsakes JG, Cho KJ. Lichen planus and lichenoid lesions of the oral cavity. Ann Otol
Rhinol Laryngol 1994;103:495.
10. Harpenau LA, Plemons JM, Rees TD. Effectiveness of a low dose of cyclosporine in the
management of patients with oral erosive lichen planus. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 1995;80:161.
11. Kyrmizakis DE, Papadakis CE. Erosive form of lichen planus. Otolaryngol Head Neck Surg
1999;121:844.
12. Cannon RD, Holmes AR, Mason AB, et al. Oral Candida: clearance, colonization, or candidiasis?
J Dent Res 1995;74:1152.
13. Porter SR, Scully C, Pedersen A. Recurrent aphthous stomatitis. Crit Rev Oral Biol Med
1998;9:306321.
14. Murray LN, Amedee RG. Recurrent aphthous stomatitis. J La State Med Soc 2000;152:1014.
15. Plevova P. Prevention and treatment of chemotherapy- and radiotherapy-induced oral mucositis: a
review. Oral Oncol 1999;35:453470.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

47 PHARYNGITIS
Head & Neck SurgeryOtolaryngology
47




PHARYNGITIS
LESTER D. R. THOMPSON
BRUCE M. WENIG
ALAN D. KORNBLUT

L.D. R. Thompson: Division of OtorhinolaryngicHead and Neck Pathology, Armed Forces Institute of
Pathology, Washington, D.C.
B.M. Wenig: Montefiore Medical Center, Bronx, New York.
A.D. Kornblut: Department of Otolaryngology, Georgetown University School of Medicine, Washington,
DC.


Anatomy
Infectious Causes of Pharyngitis
Bacterial Infections
Viral Infections
Fungal Infections
Granulomatous Diseases Causing Pharyngitis
Other Causes of Pharyngitis
Radiation Pharyngitis
Integumental Disorders
Reflux Pharyngitis
PFAPA
Idiopathic Pharyngitis
Acknowledgment
Chapter References
Pharyngitis is an inflammatory disease of the mucosal and submucosal structures of the
throat. Infection may or may not be a component of the disease. Affected tissues include
the oropharynx, nasopharynx, hypopharynx, tonsils, and adenoids. Because of their high
concentrations of lymphoid tissue, these sites are prone to reactive changes, especially in
response to pathogenic organisms. Respiratory tract infections are the most common
infectious diseases treated by primary care physicians and represent up to 80% of all
infectious disease episodes. Pharyngitis, including tonsillitis, constitutes 15% of all office
visits.
Most pharyngitides are diagnosed by clinical evaluation and usually respond to treatment
with antibiotics or symptomatic medications, or they resolve with time. Exceptions occur,
especially with infections caused by opportunistic organisms and in cases of neoplastic
growths mimicking the clinical presentations of infections. Suspected malignancies
require tissue sampling to establish a definitive diagnosis and guide appropriate therapy.
In these cases, the surgical pathologist becomes an integral member of the clinical team.
This chapter discusses the infectious and inflammatory processes of the pharynx.
Discussion about processes affecting the tonsils and adenoids is minimized, even though
their clinical presentations invariably overlap with the diagnosis and treatment of
pharyngeal disorders. Similarly, problems related to pharyngeal, parapharyngeal, and
retropharyngeal abscess formation are discussed elsewhere in this text.
ANATOMY
The pharynx is the common chamber of the respiratory and digestive tracts. It forms from
the endodermal primitive foregut and is a 12- to 14-cm musculomembranous tube that
extends from the base of the skull and the back of the nose and mouth to the level of the
sixth cervical vertebra, where it becomes continuous with the esophagus. The mucosa
that lines its upper part is covered with a pseudostratified ciliated (i.e., respiratory)
epithelium, and the mucosa in its lower part is covered with stratified squamous
epithelium.
As shown in Fig. 47.1, the pharynx has three parts: the epipharynx or nasopharynx, the
middle or oropharynx, and the hypopharynx or laryngopharynx. The upper or nasal part
of the pharynx communicates with the nose through the posterior nasal choanae. The
eustachian tube orifices are located in the superior posterolateral walls behind and
slightly below the choanae. The level of the soft palate separates the nasopharynx from
the oropharynx. The hypopharynx begins at the base of the tongue and extends inferiorly
to the inferior border of the cricoid cartilage. The larynx is positioned anteriorly, with the
epiglottis attached to the base of the tongue through the median and paired lateral
glossoepiglottic folds.

FIGURE 47.1. Clinical anatomic relationships of the
pharynx. (Adapted from Netter FH. The CIBA collection
of medical illustrations, 2nd ed. Vol. 7. Respiratory
system. Summit, NY: CIBA Medical Education, 1980;
with permission.)



The principal muscles of the pharynx are the overlapping superior, middle, and inferior
constrictor muscles. Each of these muscles inserts with its corresponding opposite muscle
in the pharyngeal raphe of the posterior midline. The quadrilateral superior pharyngeal
constrictor originates from the caudal medial pterygoid process, the pterygomandibular
raphe, the posterior part of the mandibular mylohyoid line, and the side of the base of the
tongue. These fibers give rise to the pterygopharyngeal, buccopharyngeal,
mylopharyngeal, and glossopharyngeal parts of the muscle. The pharyngeal recess (i.e.,
Rosenmller fossa) is located above the muscle's concave upper border, adjacent to the
medial part of the eustachian tube's orifice in the nasopharynx. The fan-shaped middle
constrictor muscles originate from the cornua of the hyoid bone and the lower part of the
stylohyoid ligament. The inferior constrictor muscles originate from the lateral surfaces
of the thyroid and cricoid cartilages and from a tendinous arch between both cartilages.
The fibers from the thyroid cartilage to the posterior pharyngeal wall form the
thyropharyngeus muscle, and those from the cricoid to the pharyngeal wall become the
cricopharyngeus muscle, which demarcates the pharynx from the cervical esophagus. The
upper fibers of the inferior constrictor muscle posteriorly overlap the lower fibers of the
middle constrictor muscle. The upper fibers of the middle constrictor muscle overlap the
lower fibers of the superior constrictor.
Three additional sets of longitudinal muscles pass obliquely from their origins into the
pharyngeal wall. These are the palatopharyngeus (i.e., from the anteroinferior surface of
the palate to the posterolateral oropharyngeal wall), the small sal-pingopharyngeus (i.e.,
from the nasopharyngeal orifice of the eustachian tube to blend with the palatopharyngeal
muscles in the lateral pharyngeal wall), and the stylopharyngeus (i.e., from the medial
base of the styloid process to the posterolateral pharyngeal wall, between the superior and
middle constrictor muscles).
Certain planes exist between, behind, and lateral to the pharyngeal muscles. The
buccopharyngeal fascia is the deep epimysial covering of the pharyngeal muscles. The
pharyngeal muscles are separated from the prevertebral fascia by loose connective tissue,
forming the clinical retropharyngeal space. This space is closed laterally by the carotid
sheaths. Loose connective tissue lies lateral to the pharyngeal walls and is bound laterally
by the pterygoid muscles and the thick parotid sheath. This lateral pharyngeal connective
tissue forms the lateral pharyngeal (parapharyngeal) space, which extends superiorly to
the base of the skull and is limited inferiorly at the level of the hyoid bone by the
submandibular gland's sheath and fascial attachments to the stylohyoid and posterior
digastric muscles. Although the lateral pharyngeal space is crossed by the styloglossus
and pharyngeus muscles, its connective tissue above and below these muscles is
continuous with the retropharyngeal connective tissue and the retropharyngeal space.
The principal arteries of the pharynx are derived from major branches of the external
carotid artery. These include the ascending pharyngeal artery, dorsal branches from the
lingual artery, tonsillar branches from the facial artery, and palatine branches from the
maxillary artery. The pharyngeal veins communicate superiorly with the pterygoid plexus
of veins (and the vertebral plexus) and drain inferiorly into the internal jugular vein.
Except for the stylopharyngeus muscle, which is innervated by the glossopharyngeal
nerve, the pharyngeal muscles are innervated by the vagus nerve through the pharyngeal
plexus.
The pharynx has an abundant accumulation of lymphoid and lymphonodular tissues,
especially in the mucosa of the nasopharynx and the oropharynx. The Waldeyer throat
ring of lymphoid tissue is formed by the pharyngeal, lingual, and palatine tonsils and by
lymphoid tissue on the lateral pharyngeal wall. The anatomy and function of these tissues
are discussed elsewhere.
Lymphatic drainage from the nasopharynx empties to the retropharyngeal lymph nodes
and then to the lateral pharyngeal and deep jugular nodal chains. Drainage from the
oropharynx involves the retropharyngeal nodes and the superior deep cervical and jugular
nodes. Drainage from the hypopharynx involves the retropharyngeal, lateral pharyngeal,
deep cervical, and jugular nodes.
INFECTIOUS CAUSES OF PHARYNGITIS
Bacterial Infections
The normal bacterial flora of the upper respiratory tract and oral cavity consists primarily
of gram-positive aerobic organisms, including - and -hemolytic streptococci and
several anaerobic organisms, such as Peptostreptococcus, Fusobacterium, and var-ious
Bacteroides species. These organisms and gram-positive pathogens can predominate in
clinical infections of the pharynx, although mixed infections with gram-positive and
gram-negative aerobic and anaerobic organisms are now relatively common in clinical
practice. Important pathogens include Streptococcus pyogenes, Staphylococcus aureus,
Diplococcus pneumoniae, Cory-nebacterium diphtheriae, Bordetella pertussis,
Haemophilus in-fluenzae, and Neisseria species.
Streptococcal Infection
The most frequent bacteria, implicated with pharyngitis, especially in children, is group
A -hemolytic streptococcus (Streptococcus pyogenes). Streptococcus pneumoniae,
group C streptococci, and other streptococci can cause pharyngitis. Group C and G
streptococci have been linked to severe pharyngitis and complications such as reactive
arthritis, although no causative connection has been discovered. However, these
organisms have commonly been isolated from asymptomatic patients, and it is still a
controversial issue whether patients with symptomatic pharyngitis should be treated when
these bacteria are cultured.
The incubation period for group A -hemolytic streptococcus (GABHS) lasts from 12
hours to 4 days. Patients present clinically with sore throat, difficulty swallowing, and
fever. Affected tissues are inflamed, and there is commonly an exudate. Rhinorrhea or
cough does not usually accompany this infection. Cervical lymphadenopathy is seen in as
many as 60% of patients. Streptococcal pharyngotonsillitis is less common in infants than
in older children, due to maternal immunoglobulin G (IgG) antibodies and a lack of
pharyngeal receptors for streptococcal binding. The peak incidence is from ages 5 to 15
years.
Clinical diagnosis is unreliable, although patients without fever, pharyngeal erythema and
exudate, or cervical adenitis who exhibit rhinorrhea, cough, and hoarseness can be
assumed not to have bacterial infection. In children where group A -hemolytic
streptococcus pharyngitis is suspected, diagnosis must be made to avoid the serious
complication of rheumatic fever by timely initiation of antibiotic therapy. Traditionally,
diagnosis of GABHS has been based on swab culture of the oral pharynx. Bacterial
cultures are conventionally done using regular blood agar plates. A preliminary report
including the serogroup result is usually available the next day. Serogrouping is always
preferred in the identification of -hemolytic streptococci. Two newer, rapid tests are
now on the market: the enzyme immunoassay rapid antigen test and the optical
immunoassay rapid antigen test. Both of these tests have good sensitivities (79% to 88%),
good specificities (90% to 96%), and are cheaper than culture. Results are immediately
available. Because of the risk of rheumatic fever with undertreatment of GABHS, many
recommend culture if the rapid antigen test is negative (1). In this paradigm, rapid antigen
tests are only effective in situations where the prevalence of GABHS is high; this
screening test obviates the need for culture in only about 95% of the GABHS-positive
patients and none of the GABHS-negative patients. Other evidence suggests that when
done properly, the optical immunoassay test may be more sensitive than culture for
GABHS (2). Negative optical immunoassay test results may not always need to be
confirmed by culture. A positive rapid antigen test result allows faster initiation of
antibiotics (saving 1 to 2 days of waiting) and reduces the duration of symptoms and may
reduce the spread of the disease in day care, school, and the home. However, evidence
suggests that delay in antibiotic therapy may actually reduce the likelihood of recurrent
infection in the next 4 months and increase the likelihood of GABHS eradication (3,4).
Taking into consideration the costs of the rapid antigen tests and the cost of missing or
overtreating the infection, culture of all patients has been suggested to be the safest and
most cost-effective treatment strategy (1,5). Clearly, as rapid antigen tests become more
sensitive, they will become the test of choice once the false-positive rate can be reduced
to the point where practitioners are comfortable that back-up cultures are unnecessary
following negative tests.
An alternative strategy is to treat all patients suspected of having GABHS with penicillin
or amoxicillin, which results in unnecessary antibiotic therapy in all of the patients who
do not have a bacterial infection (roughly 80% to 90% of suspected cases). Many studies
have shown that the use of antibiotics in pharyngitis patients with negative throat cultures
for GABHS or other known bacterial pathogens has little or no efficacy. This approach
risks development of antibiotic-resistant bacterial strains and may lead to side effects
from the medication and thus is discouraged as poor medical practice.
Treatment of streptococcal pharyngitis is by oral or intravenous administration of
penicillin, and patients allergic to penicillin can be treated with erythromycin or a variety
of cephalosporins. Oral penicillin is effective in both twice and thrice daily dosing (1,4).
Failure of penicillin therapy in GABHS pharyngitis is felt to be due to elimination of
normal flora, especially -hemolytic streptococci, which compete with the GABHS, or -
lactamaseproducing organisms, which protect the GABHS by breaking down the
penicillin (6). Failure to eradicate the GABHS, however, does not equate with failure to
prevent rheumatic fever; therefore, broader spectrum antibiotics are not indicated in this
disease. First-generation cephalosporins are recommended for treatment failures.
Complications of streptococcal infections include rheumatic fever, rheumatic heart
disease, and acute, poststreptococcal glomerulonephritis (i.e., Bright disease). Grisel
syndrome, subluxation of the atlantoaxial joint due to an infectious inflammatory process
of the head and neck, can also infrequently result from streptococcal pharyngitis. These
patients present with atraumatic torticollis and a history of recent head and neck infection
or surgical procedure. The incidence of the disease varies with the age of the patient,
season, climate, and living conditions.
Rheumatic fever is diagnosed based on the presence of two major (or one major and two
minor) criteria with evidence of preceding GABHS infection (Table 47.1) (7). Evidence
of antecedent group A streptococcal infection may be from throat culture, rapid antigen
tests, or an elevated or increasing streptococcal antibody titer. Patients with acute
rheumatic fever are at high risk for recurrent attacks, even with subclinical GABHS
infections, and therefore should be given antibiotic prophylaxis (8). The introduction of
antibiotics has reduced the mortality rate from rheumatic fever by over fivefold, despite
the fact that 80% to 90% of patients with pharyngitis do not seek medical care. The risk
of developing rheumatic fever during an epidemic is estimated to be 3% of patients with
GABHS who do not receive antibiotics, whereas only 0.3% of patients with endemic
untreated GABHS develop this complication. The risk of developing glomerulonephritis
is not reduced by the use of antibiotics.

TABLE 47.1. DIAGNOSIS MODIFIED JONES
CRITERIA FOR THE DIAGNOSIS OF INITIAL
ATTACK OF RHEUMATIC FEVER



Scarlet fever is an acute streptococcal pharyngotonsillitis accompanied by a rash and
production of an erythrogenic toxin. Toxin production depends on lysogeny of the
infecting organism by a temperate bacteriophage. The characteristic rash usually appears
on the second day of illness and is red and punctate. This rash initially appears on the
chest and trunk and subsequently spreads to cover virtually the entire body within several
hours. The face, palms, and soles are spared. The rash blanches under pressure and fades
over the course of a week, although desquamation can occur in some cases. Another
characteristic finding is the strawberry tongue. The tongue is swollen, red, and mottled.
Diagnosis is based on culture results.
Scarlet fever rarely affects infants because of placental transfer of maternal antibodies to
the erythrogenic toxins or because of prior hypersensitization to the erythrogenic toxins.
Severe forms of scarlet fever characterized by systemic toxicity resulted in a 5% death
rate 100 years ago, but this rarely occurs since the advent of antibiotic therapy. Eventual
elimination of this disease may result from development of a vaccination.
Staphylococcal Infection
Pharyngitis due to S. aureus (or S. salivarius) may be associated with mucopurulent
drainage, mucosal erythema and edema, and localized pustules, especially in the tonsils.
Erythema and edema are also common findings. Staphylococcus can be treated with anti-
staphylococcal penicillins, erythromycin, or cephalosporin antibiotics based on culture
and sensitivity results.
Diphtheroid Infection
In the past, Corynebacterium species have been common causes of pharyngitis. Most
species are rarely pathogenic in humans, with the notable exception of C. diphtheriae.
This organism is uncommonly seen in developed countries and where routine
vaccinations are used. Diphtheria is more common in children under 10 years of age (9).
The diphtheroid organisms are gram-positive, nonfilamentous rods that gain access to the
host by the nose and mouth and then remain localized in the mucosal surfaces of the
upper re-spiratory tract. After a short incubation period of 2 to 4 days, exotoxins may be
produced that cause localized tissue necrosis and inflammation. The combination of these
responses produces a gray-black membrane that is firmly adherent to the underlying
tissue and may widen with continued toxin production to extend to the mucous
membranes of other upper aerodigestive tract sites. Extension of the membrane to the
nasopharynx or the larynx and hypopharynx may be severe, leading to an inability to
clear secretions and to respiratory obstruction. Moreover, toxin may enter the
bloodstream and lymphatic vessels, especially if the pharynx and tonsils are infected.
Because of the potential for respiratory and circulatory collapse (myocardial
insufficiency), prompt diagnosis and treatment must be established. Antitoxin remains the
only specific method of treatment. Antibiotics (e.g., penicillin, erythromycin) are useful
as adjuvant therapy in infected patients and in asymptomatic carriers.
Pertussis
Bordetella pertussis causes an acute, highly communicable childhood disease that is
characterized by violent paroxysms of coughing accompanied by a loud inspiratory
sound. This latter sound accounts for the term whooping cough. B. pertussis is a
nonmotile, pleomorphic, gram-negative coccobacillus that infects the host after inhalation
and multiplies only in association with ciliated epithelium (10).
The incubation period is approximately 1 week and is followed by three clinical stages.
The first is the catarrhal stage, which lasts from 1 to 2 weeks and is marked by a low-
grade fever and upper respiratory symptoms. It is followed rapidly by the paroxysmal
stage, in which the characteristic cough occurs. There is no fever during this stage. The
organism produces endotoxins and agglutinogens and has a strong affinity for the brush
border of ciliated columnar epithelium, where it proliferates and from whence its toxin
diffuses. The organism remains superficially located on the surface epithelium, with
epithelial necrosis becoming evident in the paroxysmal stage of infection, which is
characterized by a mucopurulent exudate. The paroxysmal stage lasts 2 to 4 weeks or
longer and is followed by a 1- to 2-week convalescent stage.
The disease can be prolonged in its clinical course but is generally self-limiting, and
death rarely occurs. Antibiotics do not alter the course of the disease. Immunization has
nearly eradicated whooping cough in developed countries, so infection is now associated
with underdeveloped countries.
Gonorrhea
Neisseria gonorrhoeae, a pyogenic gram-negative diplococcus, is an important cause of
pharyngitis among the diseases transmitted by sexual contact. Gonococcal pharyngitis
generally is asymptomatic but may present with sore throat, tonsillar hypertrophy, or
cervical adenopathy. Gram stain for smears from the pharynx is unreliable because of the
presence of other organisms; samples must be cultured on appropriate media (e.g.,
chocolate agar) for identification. The organism infects mucosal and glandular structures,
where it causes ulcerations of the epithelium and a polymorphonuclear leukocyte
infiltrate. The organisms are difficult to identify in tissue sections but can be
demonstrated in leukocytes after Gram or methylene blue staining. Gonococcal
pharyngitis may be the source of continued transmission or may lead to disseminated
disease. Effective treatment with penicillin, tetracycline, cephalosporins, or quinolones is
dictated by the culture sensitivities and patient compliance.
Syphilis
Syphilis is a systemic venereal disease whose protean clinical manifestations include
involvement in the head and neck. Syphilis is caused by Treponema pallidum, a member
of the family Spirochaetaceae, which includes T. pertenue (yaws) and T. carateum
(pinta). The clinical stages of syphilis are primary, secondary, tertiary, and congenital,
any of which can affect the head and neck. After an incubation period that varies from 3
to 90 days (median 3 weeks), a painless solitary chancre appears at the site of inoculation.
This is the primary stage, and the tonsils may be among the various head and neck sites
affected. The chancre initially appears as a papule, which then ulcerates and is
surrounded by raised, indurated margins. Microscopically, an inflammatory infiltrate is
predominantly composed of plasma cells with scattered histiocytes, lymphocytes, and
polymorphonuclear leukocytes. This infiltrate has a tendency to involve small blood
vessels, which display endothelial cell proliferation. Concentric layers are produced that
markedly narrow affected vessel lumina. Obliterative endarteritis, coupled with the in-
flammatory infiltrate produced by the spirochetes, represents the histologic hallmarks of
the disease. Organisms can be demonstrated from the chancre by a variety of techniques,
including dark-field examination of smears, immunocytochemistry, or tissue sections
with Warthin-Starry staining. The chancre usually heals spontaneously in 3 to 6 weeks.
From 2 to 8 weeks after the development of the chancre, the secondary or disseminated
stage of syphilis occurs. Evolution into the secondary stage also may occur while the
chancre is still present. During this secondary stage of infection, the spirochetes multiply
and disseminate from the primary lesion to all organ systems. Skin lesions and
lymphadenopathy are seen in 90% of patients in this stage. Pharyngotonsillitis may be a
presenting symptom in secondary syphilis, and mucosal involvement produces mucous
patches. These patches are characterized by painless, superficial erosions with a silver-
gray appearance and are surrounded by raised, red peripheral margins. These lesions are
highly contagious. Microscopically, they resemble lesions of the primary chancre but
with a less intense plasma cell infiltrate, which is usually confined around vascular
spaces. Among untreated, second-stage patients, one third experience inactivation of
disease with spontaneous remission, one third continue with latent disease, and one third
progress to tertiary syphilis.
Tertiary syphilis may develop years after the initial infection and is slowly progressive,
usually involving the central nervous system or the aorta. Localized, nonprogressive
lesions also may develop. These gummas histologically represent a granulomatous
process consisting of central coagulative necrosis surrounded by palisading macrophages
and fibroblasts. Treponemes are scant and extremely difficult to identify. The gummatous
reaction represents a pronounced immunologic reaction of the host.
There are two types of serologic tests for syphilis: the nonspecific nontreponemal
antibody tests and the specific treponemal antibody tests. The nontreponemal antibody
tests (which are inexpensive, rapid, and indicate disease activity) include the Venereal
Disease Research Laboratory (VDRL) test and a modification of this test called the rapid
plasma reagin test. These tests are most reactive in the secondary stage of disease, with
99% of syphilitic patients eliciting positive reactions. The principal treponemal antibody
test (which is time consuming and expensive) is the fluorescent treponemal antibody
absorption test (FTA-ABS). This test is sensitive and reliable, with positive reactions in
85% of patients with primary disease, 100% of patients with secondary disease, and 98%
of patients with tertiary disease. The VDRL and rapid plasma reagin test should be used
as screening tests, with the FTA-ABS reserved for confirmation and for diagnosis in the
late stages of disease. False-positive serologic tests are caused by an array of infectious
and noninfectious diseases, usually with the nontreponemal tests. Treatment of syphilis
remains penicillin. For patients allergic to penicillin, tetracycline or erythromycin are
effective alternatives.
Other Bacterial Infections
Other pathogenic organisms producing reported cases of bacterial pharyngitis include
Salmonella typhimurium, Fusobacterium necrophorum, and F. nucleatum (occasionally
causing Lemierre syndrome: pharyngitis followed by sepsis and jugular
thrombophlebitis), Yersinia enterocolitica, Arcanobacterium haemolyticum (which may
manifest as an extensive exanthematous eruption of the skin that mimics scarlet fever),
Moraxella catarrhalis, Francisella tularensis, Mycoplasma species, Neisseria
meningitidis, and Chlamydia species. Coxiella burnetii (a rickettsial organism), the
causative agent of Q fever, may cause pharyngitis. The organisms can be identified by
culture, immunoassay, latex agglutination, in situ hybridization, or polymerase chain
reaction (PCR). Rhinoscleroma is a rare chronic granulomatous disease that primarily
involves the nasal cavity. Infrequently, infection occurs in the pharyngeal region.
Viral Infections
Viruses are the most common cause of pharyngitis and may closely mimic the clinical
presentation of bacterial pharyngitis. In such cases, mucosal edema and erythema are
common, but mucopurulent drainage generally implies primary or secondary bacterial
infections. The absence of a positive bacterial culture and failure to resolve with
antibiotic treatment also can aid in differentiating the cause of the infection. If indicated
clinically, viral cultures or acute and convalescent sera for viral titers can be performed,
but these usually are unnecessary and costly, especially because management is usually
symptomatic.
Herpes Simplex Virus
Herpes simplex virus (HSV) has two serologically distinct subtypes: type 1 (usually oral)
and type 2 (usually genital). However, the virus type is not necessarily a reliable indicator
of the anatomic site affected. Herpes simplex virus infection of the upper aerodigestive
tract occurs in both primary and recurrent forms.
Primary HSV infection most frequently presents as a gingivostomatitis but may present
as an acute pharyngitis. Only 25% to 35% of patients presenting with HSV pharyngitis
had concomitant gingivostomatitis. HSV has a tendency to infect cells of ectodermal
origin, usually in skin or mucous membranes. Primary HSV-induced infection occurs
most frequently in children 10 months to 3 years of age. Before the age of 10 months,
residual maternal antibodies probably play a role in preventing recognizable symptoms
related to primary HSV infection. In adolescents, primary HSV infection can present as
an acute posterior exudative pharyngitis. In college-age individuals, HSV pharyngitis is
seen more commonly than streptococcal pharyngitis or influenza.
The virus may be transmitted by mucus or saliva or acquired from infected paronychial
sites by nail biting or thumb sucking. The incubation period is relatively short, lasting
from 2 to 12 days, after which appear the clinical manifestations of malaise, fretful
behavior, fever, and pharyngitis. Infection of the pharynx may appear as vesicular lesions
that bleed easily and are covered with a black crust or as shallow tonsillar ulcers covered
with a gray exudate. Cervical lymph node enlargement and tenderness also may be
observed. The acute illness evolves over 7 to 10 days, followed by rapid regression of
symptoms and resolution of lesions, correlated with the development of neutralizing
antibodies, detectable after the first week. Although primary HSV infection is usually
self-limiting, disseminated infection also may develop, including central nervous system
involvement. Conditions contributing to severe HSV infection or disseminated disease
include neonatal infection, malnutrition, primary immunodeficiency disorders,
immunosuppressive therapy, pregnancy, burns, trauma, skin abnormalities (such as atopic
eczema, bullous impetigo, and pemphigus), concurrent bacterial infections, sarcoidosis,
and malignancy. Viral dissemination is associated with mortality rates as high as 80%.
After primary HSV infection, the virus can remain latent in infected tissues and can be
reactivated under a variety of stimuli, including fatigue, stress, physical trauma, and
fever. It is thought that HSV resides latent in sensory neural ganglia innervating the
originally involved sites, and reactivation results in disease occurring at or near the
original site of infection. Recurrence in immunocompetent persons is usually less severe
than the primary infection. The immune response to primary HSV infection consists of an
early nonspecific response followed by a specific immunologic response, including
antiviral neutralizing antibodies, complement-fixing antibodies, and antibodies to specific
viral glycoproteins.
Histopathologic findings include ulceration of affected mucosal surfaces associated with
a mixed acute and chronic inflammatory infiltrate, including multinucleated giant cells
and intranuclear inclusions. Identification of the virus can be accomplished by
immunocytochemistry.
The diagnosis of HSV infection can be made by several methods. Tissue culture is
specific but requires 12 to 48 hours to generate typical cytopathic effects. A more rapid
but less specific method is cytologic examination and, rarely, electron microscopy. The
rapid and specific methods for detecting HSV include fluorescent antibody assays,
enzyme-linked immunosorbent assays (ELISAs), radiometric tests, and
immunoperoxidase-tagged antibody in ELISAs or tissue sections. Newer molecular
biologic techniques include in situ hybridization and PCR, which offer the potential for
rapid, specific, and sensitive means of detecting active and latent infections. Management
is essentially symptomatic. Inhibitors of viral nucleic acid replication (acyclovir) have
been prescribed but are best reserved for immunocompromised patients.
Measles
Rubeola (i.e., measles) is a morbillivirus that is highly contagious, causing an acute
febrile, systemic infection. Clinical symptoms usually begin with coryza and
conjunctivitis, followed by the typical spotty exanthematous lesions on the buccal
mucosa (i.e., Koplik spots), lymphoreticular hyperplasia, and a generalized cutaneous
erythematous rash. In the pharyngeal area, measles causes a marked follicular hyperplasia
of all lymphoid tissue that is associated with multinucleated giant cells. Treatment of
measles is symptomatic, and the disease course is usually benign and self-limiting.
However, in the very young, very old, or immunosuppressed patient, high mortality rates
result from the consequences of neural, cerebral, or visceral involvement or as a result of
bacterial superinfections.
Epstein-Barr Virus
Epstein-Barr virus (EBV), also a member of the family Herpesviridae, selectively infects
B-lymphocyte populations. Naso-pharyngeal undifferentiated carcinoma and African
Burkitt lymphoma have been strongly associated with EBV, but there is only indirect
evidence suggesting EBV as the causative agent. In contrast, EBV has been demonstrated
conclusively to be the cause of infectious mononucleosis (IM), a systemic infection
primarily occurring in adolescents and young adults. EBV has been estimated to cause
80% to 95% of mononucleosis cases. Other microorganisms associated with
mononucleosis-like syndromes include cytomegalovirus (CMV), Toxoplasma gondii,
rubella, hepatitis A virus, human immunodeficiency virus (HIV) type 1, and
adenoviruses.
EBV-associated infectious mononucleosis may resemble acute pharyngotonsillitis, with
patients experiencing sore throat, fever, and malaise. Lymphadenopathy, splenomegaly
(50%), and hepatomegaly (10%) with chemical evidence of hepatitis may represent the
systemic manifestations of the disease. Rupture of an enlarged spleen is a serious
complication of the disease. Hepatosplenomegaly is most prominent during the second to
fourth weeks of illness. A prodromal period of malaise and fatigue for 2 to 5 days usually
precedes the onset of the full syndrome. The pharyngotonsillitis incurred is often severe
and may be exudative. Lymphadenopathy, most commonly of the posterior cervical
lymph nodes, but of any lymph nodes, can be found.
The diagnosis of infectious mononucleosis is routinely based on clinical manifestations
and appropriate laboratory findings, usually without tissue confirmation. Patients with
infectious mononucleosis typically demonstrate an absolute lymphocytosis, with more
than 50% lymphocytes in a total leukocyte population of more than 5,000/mm
3
and
prominent atypical lymphocytes that are often more than 10% of the total leukocyte
count. Mild to moderate elevations of liver enzymes commonly occur. Diagnosis can be
confirmed by the demonstration of serum heterophile antibodies to either horse or sheep
erythrocytes (usually a positive Mono-Spot test); however, children under 10 years of age
with EBV-associated infectious mononucleosis often will not have a positive heterophile
antibody test result, and serologies may need to be repeated, especially during the first
month of infection, before a diagnosis is made. Negative heterophile antibody testing also
can occur in IM as a result of infectious agents other than EBV (i.e., CMV).
After the incubation period, patients developing infectious mononucleosis typically have
about 1% of their circulating B-lymphocytes infected with EBV, but this incidence may
reach as high as 20%. The atypical lymphocytes in the peripheral blood are thought to
represent mostly activated T-lymphocyte populations in response to B-cell infection.
Agents other than EBV implicated in infectious mononucleosis are not associated with a
positive heterophile antibody test.
In the atypical cases of IM, in which the patient presents with adenotonsillar or lymph
node enlargement without fever, sore throat, or splenomegaly, a biopsy may be needed to
establish a diagnosis and rule out malignancy (e.g., lymphoma). Microscopically, the
lymphoid tissue displays reactive follicular hyperplasia with marked mitotic activity,
phagocytosis, and expansion of the interfollicular areas that may result in distortion or
effacement of the parenchymal architecture. There is a proliferation of immunoblasts,
plasma cells, Reed-Sternberglike cells, and lymphocytes. Necrosis is usually focal but
occasionally may be extensive. The cellular proliferation may display marked cytologic
atypia and may lead to erroneous interpretations of non-Hodgkin malignant lymphomas
or to Hodgkin lymphomas. Microscopic differentiation may prove difficult; in such cases,
the clinical presentation and laboratory findings become critical. Furthermore, molecular
biologic analysis evaluating for the presence of gene rearrangements and monoclonality,
features that are usually indicative of a malignant lymphoproliferative disorder, may
prove invaluable in the differentiation of IM from malignant lymphoma.
In patients who consistently prove to be heterophile antibody (Mono-Spot) negative,
serodiagnosis is invaluable. At the time of clinical presentation, there is an appreciable
serum response to EBV viral capsid antigen (VCA) with IgM and IgG antibodies. At the
same time or shortly thereafter, many infected patients develop antibodies to early
antigen complex. During the early phase of primary infection, antibodies to EBV nuclear
antigens (EBNA) are usually not demonstrable. IgM antibodies to VCA disappear within
2 to 3 months after infection, antibodies to early antigen complex disappear within 2 to 6
months after infection, and IgG antibodies to VCA and anti-EBNA antibodies persist for
life and indicate a chronic carrier state. Recent advances in molecular biologic techniques
permit the generation of proteins containing EBV-encoded polypeptide sequences and
represent a more reliable and sensitive means for detecting the virus than serodiagnosis.
The clinical course for patients with infectious mononucleosis is usually favorable, with
resolution of symptoms within several months. Therapy is supportive, including rest and
fluids.
Cytomegalovirus
Cytomegalovirus is a member of the family Herpesviridae and has several antigenically
distinct strains. Since its isolation, CMV has been identified as the cause of congenital
and acquired infections. Most infections caused by CMV are asymptomatic, except in
immunocompromised patients. Transmission of the virus can occur by ingestion of
human milk; by contact with saliva, semen, or cervical secretions; and by infusion of
peripheral blood leukocytes. The cells have a characteristic intranuclear or cytoplasmic
inclusion associated with cellular and nuclear enlargement. The virus can be detected
through viral isolation, serology, or PCR (11). A CMV infection should be distinguished
from an EBV infection. Unlike EBV mononucleosis, patients with CMV-associated
infectious mononucleosis usually do not present with pharyngitis and are heterophile
antibody negative. The most effective and sensitive method to detect active CMV
infection is urine culture with inoculation of human diploid cell culture (11).
Serodiagnosis also can be used and includes complement fixation testing.
Human Immunodeficiency Virus Type 1
There has been a recent increase in the number of patients affected with HIV type 1,
especially in association with acquired immunodeficiency syndrome (AIDS). In these
patients, the changes of pharyngitis can be seen, in addition to abnormalities in the
tonsils. Viral particles have been documented in the pharyngeal epithelium and tonsils,
especially with PCR and immunohistochemical analysis. As the pharynx is covered with
a lymphoepithelium, one can expect to find the changes associated with HIV if sought in
the appropriate clinical setting (12).
Acute retroviral syndrome occurs in some patients during primary infection of HIV. Sore
throat is part of a constellation of signs mimicking EBV that lasts from a few days to
weeks. Other features include fever, malaise, myalgia, arthralgia, photophobia,
lymphadenopathy, and maculopapular rash.
Fungal Infections
Fungal and parasitic infections generally are not implicated in causing pharyngitis, except
in immunosuppressed patients or patients who are chronically debilitated. In these
patients, the organisms represent opportunistic agents and may produce systemic disease
with lethal consequences. This patient population includes those with cancer, transplant
patients undergoing treatment with immunosuppressive agents, and those with AIDS.
Patients receiving treatment with antimicrobial agents may have their host defenses
altered by antibiotics, impairing the capacity for phagocytizing microorganisms, and may
develop a change in normal flora, leading to colonization and infection by normally
saprophytic organisms.
Candidal Infections
Of the fungal infections potentially infecting the pharynx, Candida albicans is the most
frequent offender. In the upper aerodigestive tract, Candida species normally reside in the
mouth, but if the immune system is compromised, invasion of the mucosal surfaces can
occur, causing pain or dysphagia. This disease is most typically seen in HIV-positive
patients and after radiotherapy for head and neck cancer. Typical lesions appear as cheesy
or creamy mucosal plaques. Identification of the organism is accomplished easily by
Gram stain or periodic acid-Schiff stain of a smear or by culture on Sabouraud agar.
Histologically, budding yeasts and pseudohyphae with an associated inflammatory
infiltrate are seen after staining with periodic acid-Schiff or silver stains. Treatment of
candidiasis limited to the oral cavity or the pharynx is with topical nystatin or oral
ketoconazole or fluconazole. Prophylaxis with oral fluconazole is effective in HIV-
positive patients to reduce the incidence of infection (13). If oral or pharyngeal infection
represents part of systemic involvement, amphotericin B may be necessary.
Deep-seated Mycoses
Other fungi can infect a variety of head and neck sites, although specific involvement of
the pharyngeal region by these organisms is rare. Such organisms include Cryptococcus
neoformans, Rhinosporidiosis seeberi, Histoplasma capsulatum, Blastomyces
dermatitidis, and Paracoccidioides brasiliensis.
GRANULOMATOUS DISEASES CAUSING PHARYNGITIS
A granuloma is a chronic inflammatory process that is defined by the presence of
modified macrophages (or epithelioid histiocytes), usually surrounded by other
inflammatory cells, with giant cells and fibroblasts. Granulomatous inflammation can be
seen associated with bacteria, mycobacteria, fungi, syphilis, parasites, sarcoid, Wegener
granulomatosis, Crohn disease, and neoplasms. If confronted with a presumed infectious
process that is unresponsive to empirical antibiotic therapy, appropriate cultures and
biopsy sampling of affected tissues are necessary. Wegener granulomatosis and
sarcoidosis are discussed elsewhere in the text and rarely involve the pharynx.
In the United States, infection caused by Mycobacterium tuberculosis is relatively
uncommon in the head and neck, and involvement of the pharynx is rare. Nevertheless,
mycobacterial pharyngotonsillitis still can occur as a result of expectoration of infected
sputum from pulmonary involvement or as an isolated occurrence, especially in patients
from poor socioeconomic regions (14). Clinical presentation can include sore throat, with
nasal obstruction, cervical adenopathy, and pulmonary symptoms. Both M. tuberculosis
and M. bovis have been implicated in mycobacterial pharyngotonsillitis (14).
Leprosy (i.e., Hansen disease) is a chronic infectious disease caused by Mycobacterium
leprae. Involvement of the pharynx occurs only after the nasal cavity is affected (15). M.
leprae is an acid-fast bacillus, but this quality is weaker than in other mycobacteria. The
mode of transmission of M. leprae has not been definitively established. Although skin-
to-skin contact has been considered the most important means of transmission, this
concept has been challenged in recent years. Because the sinonasal mucosa in an infected
person is a site harboring massive numbers of bacilli, the upper respiratory tract could
represent a source of infecting bacilli.
Leprosy has been classified as lepromatous or tuberculoid. These forms represent the
patient's immunologic response after an intradermal injection of a suspension of killed M.
leprae prepared from lepromatous tissue. This lepromin reaction appears as an area of
induration and exhibits an early response at 48 hours and a late response at 3 to 4 weeks
(Mitsuda reaction). The Mitsuda reaction is considered the most consistent and is used as
an aid for classifying the clinical forms of leprosy. Although not useful in the general
population as a diagnostic tool, because it is frequently positive, it is useful as a
prognostic tool because it directly measures the cell-mediated immunity potential of the
host to M. leprae infection. In patients with tuberculoid leprosy, the Mitsuda reaction is
strongly positive (>5 mm in diameter); in lepromatous leprosy, this reaction is weak or
negative (0 to 2 mm); and in borderline patients, the response is intermediate (3 to 5 mm).
The histopathologic appearance of affected tissues depends on the type of leprosy. A
noncaseating granulomatous process with or without giant cells characterizes tuberculoid
leprosy. Nerve damage is distinctive, with rare bacilli identified within the nerve. In
lepromatous leprosy, there is a proliferation of foamy macrophages (lepra cells)
containing large numbers of bacilli, but no granulomas are formed, reflecting the anergic
response of the patient to the organisms. Bacilli can be seen in nerves and endothelial
cells. Biopsy specimens should be taken from the active border of the lesion (15).
Treatment consists of chemotherapy, including dapsone, clofazimine, and rifampin. With
adequate treatment, prognosis is good for most patients. The initiation of early therapy
also helps to prevent subsequent deformities or mutilation.
Granulomas due to parasitic infections of the pharyngeal region are rare. Among the
parasites that may infect the pharynx are Leishmania braziliensis, Toxoplasma gondii,
Clinostomum complanatum, and Mammomonogamus laryngeus, but these infections
usually occur only in endemic regions in the world.
Noninfectious granulomatous pharyngotonsillitis may result from foreign bodies or
pharyngeal involvement by systemic disease. Foreign-body granulomas result as a
response to exogenous materials introduced into the body by trauma, iatrogenically, or by
abnormal deposition of materials such as keratin or hair. The body's reaction is to wall off
these substances by the development of a granuloma, within which the causative agent
can generally be identified. Although uncommon in the pharynx or tonsillar region,
foreign body granulomas can simulate an infectious process.
Crohn disease is a granulomatous, inflammatory process of unknown etiology that
primarily affects the small and large intestines. Pharyngeal involvement by Crohn disease
may be seen in 9% of patients during the course of their disease and usually follows
intestinal manifestations. Infrequently, pharyngeal Crohn disease precedes intestinal
disease and is rarely the sole manifestation of disease. Activity correlates with intestinal
disease, and resolution may follow treatment of the intestinal disorder.
Systemic or discoid lupus erythematosus frequently manifests with oral and pharyngeal
ulcers.
OTHER CAUSES OF PHARYNGITIS
Radiation Pharyngitis
Oral and pharyngeal mucosa has a very high cell turnover rate and goes into atrophic
changes due to inhibition of cellular division by radiation therapy at doses of 16 to 22
cGy. Prevention is impossible; this is an inevitable side effect of head and neck radiation.
Saliva is reduced due to effects on the major and minor salivary glands, which
predisposes the pharynx to superinfection by bacterial or fungal organisms. Treatment for
radiation pharyngitis is symptomatic. Oral concoctions including sucralfate,
diphenhydramine, antibacterial agents, and topical steroids are frequently used to treat the
acute radiation damage. Pilocarpine is used both during and following radiation to
increase salivary flow. Specific treatment for superinfection includes topical antifungals
(nystatin) or systemic antifungals or antibiotics.
Integumental Disorders
Stevens-Johnson Syndrome
Stevens-Johnson syndrome (also known as exudative erythema multiforme) occurs in
children and young adults, with males affected more frequently than females. The cause
is unknown, but onset may follow an upper respiratory infection or the use of certain
drugs, especially sulfonamides, anticonvulsants, and barbiturates. The syndrome is
characterized by an angiitis producing an erythematous vesicular skin lesion, which may
become bullous. In the acute phase, fever and prostration are common; up to 10% of
patients die, especially those with pulmonary involvement (16). Painful vesiculobullous
lesions can be found in the mucosa of the mouth, pharynx, and larynx, with the lesions
commonly ulcerating, bleeding, and crusting. Mucosal lesions can precede skin lesions.
Histologically, a zone of liquefaction degeneration can be seen in upper epithelial layers,
with basement membranes frequently absent and with intraepithelial vesicles and
subepidermal bullae occurring.
The syndrome is usually self-limited, with the skin lesions resolving in approximately 4
weeks, slightly longer for the mucosal lesions. Twenty percent of patients may
experience recurrences, especially with reexposure to causative drugs. Treatment is
generally symptomatic, with maintenance of fluid and electrolyte balance during the
disorder's acute phase and treatment of secondary infections. Withdrawal of the offending
agent (whether drug or other sensitivity) is essential (16).
Pemphigus
Pemphigus is an important but uncommon disease of skin and mucous membranes.
Vesicles and bullae appear in cycles on affected sites. There is no gender predilection,
and the disease usually appears in patients over 30 years of age. An autoimmune
mechanism is thought to be responsible because intercellular antibodies have been
demonstrated in involved tissues and circulating intercellular antibodies have been
detected in patients' sera (17).
The disease has been separated into many types, a number of which can appear in the
pharynx: pemphigus vulgaris, pemphigus vegetans, pemphigus foliaceus, pemphigus
erythematosus, pemphigus herpetiformis, drug-induced pemphigus, IgA pemphigus, and
paraneoplastic pemphigus (18). Pemphigus vulgaris is characterized by the rapid
appearance of various-sized vesicles and bullae, often involving large surface areas.
Rupture of the bullae leaves raw, eroded defects. Lesions bleed easily and can be painful
enough to prevent eating or swallowing. Profuse salivation can occur, and poor oral
hygiene results in secondary infections. The oral lesions of pemphigus vegetans tend to
have vegetations similar to condyloma with a serpiginous pattern, the surfaces resembling
pus. Removal of the lesions' surface leaves a nonbleeding, moist, red base, which is
usually not painful (18). The Nikolsky sign (rubbing unaffected areas resulting in
sloughing) usually is not seen in the mucosal sites. The clinical course of any pemphigus
is variable, with periods of remissions and exacerbations, often resulting in early patient
death.
Histologically, affected tissues contain intraepithelial vesicles or bullae that produce a
distinctive suprabasilar split. Prevesicular edema is common, and intercellular bridges
between epithelial cells disappear to produce acantholysis. These changes result in
clumps of epithelial cells (i.e., Tzanck cells) lying free within vesicular spaces. Cells
show degenerative changes, with nuclear swelling and hyperchromasia. Fluid fills most
of the vesicles or bullae, which may contain scant numbers of polymorphonuclear
leukocytes and lymphocytes. Treatment includes steroids, immunosuppressive agents,
and antibiotics for secondary infections (18).
Familial benign chronic pemphigus is an uncommon disorder that is transmitted by an
irregularly dominant gene. Patients may not know of any family history of the disease,
and several generations may be spared. It is believed that the disease represents a flawed
synthesis or maturation of the tonofilament and desmosome complex. Histologically,
features are similar to those found in pemphigus vulgaris but with more extensive
acantholysis and usually less damage to acantholytic cells. Persistence of occasional
intercellular bridges allows adjacent epithelial cells to adhere to each other and produce
the appearance of a dilapidated brick wall. Benign-appearing dyskeratotic cells also may
be present. Treatment is symptomatic, with antibiotics given for secondary bacterial
infections. Long remissions are common, and the disease often becomes less severe as
the patient ages.
Cicatricial Pemphigoid
Cicatricial pemphigoid (benign mucous membrane pemphigoid) is a vesiculobullous,
probably autoimmune disease (19). Women are frequently affected, with the peak
involvement during middle age. Vesiculobullous lesions typically occur on the
conjunctiva and upper airway mucosa, and there is occasional skin involvement (19). The
oral mucosal lesions can persist 24 to 48 hours before desquamation leaves eroded,
bleeding tissue surfaces; scarring is infrequent. Histologic features are nonspecific,
showing subepidermal vesicles and bullae without acantholysis. A chronic nonspecific
inflammatory infiltrate also can be present. Treatment is supportive, with steroids and
cyclophosphamide or other immunosuppressants used for severe disease (19).
Bullous Pemphigoid
Bullous pemphigoid (or parapemphigus) is a disease of the elderly: most patients are over
60 years of age. There is no sex predilection. Cutaneous lesions begin as a generalized
nonspecific rash that persists for varying periods of time before vesiculobullous lesions
appear. If these lesions rupture, they leave raw, eroded surfaces that usually heal rapidly.
The disorder is similar to cicatricial pemphigoid, although oral mucosal lesions occur less
frequently (20,21).
Histologically, the subepidermal vesicles and bullae tend to be nonspecific. The vesicles
contain a fibrinous exudate with some inflammatory cells. Electron microscopy of
affected tissues has demonstrated that the epithelial basement membrane remains
attached to underlying connective tissue and that there are alterations of blood vessels.
The basement membrane shows thickening and interrupted continuity. In affected
patients, circulating basement membrane zone antibodies and tissue-bound, anti
basement membrane antibodies have been demonstrated (20,21). Spontaneous remissions
have occurred, and cortico-steroids have been useful in treatment.
Epidermolysis Bullosa
Epidermolysis bullosa is an unusual group of congenital and acquired dermatologic
diseases in which bullae or vesicles affect skin and mucous membranes with various
degrees of severity. Onset can follow trauma or occur spontaneously. The recessive form
is the classic form of the disease, occurring at birth or in early childhood. Oral lesions can
be preceded by the appearance of white spots or patches or the development of localized
areas of inflammation. Ruptures of bullae leave raw, painful surfaces that heal by
scarring. In the oral cavity, scarring can obliterate normal sulci and restrict tongue
movements. Hoarseness and dysphagia can result from laryngeal or pharyngeal
involvement, and strictures can occur in the esophagus. These changes are extensive in
the lethal form of the disease, and affected patients usually die in early infancy (22).
Histologically, epithelial separation and bulla formation occur immediately beneath a
poorly defined basement membrane that remains attached to the roof of the bulla.
Fragments of basement membrane also can be found adhering to dermis. Because there is
no known cure for any form of this disease, treatment is symptomatic, with antibiotics
used for secondary infections. Steroids have been used in some patients, but results have
been inconsistent (22).
Reflux Pharyngitis
Gastroesophageal reflux disease (GERD) has become a frequently recognized source of
pharyngeal and laryngeal pathology caused by irritation of pharyngeal structures by
gastric contents. It has been associated with hoarseness, sore throat, chronic cough,
globus pharyngeus, halitosis, cervical dysphagia, and esophageal and laryngeal
carcinoma. Mild pharyngeal erythema and posterior pharyngeal cobblestoning may be
pres-ent, but the most reliable sign of this disease on head and neck examination is
arytenoid erythema. The patient will often complain of excessive phlegm but often will
not complain of heartburn (23). The most accurate diagnostic test is 24-hour esophageal
pH monitoring with both proximal and distal sensors. However, this test is expensive and
invasive. Because GERD is so pervasive in the adult population with globus pharyngeus
and chronic pharyngitis and otherwise normal head and neck examinations, empiric
therapy for GERD with dietary and life-style modification (reflux precautions) and
pharmacotherapy with either histamine-2 receptor blockers or proton pump inhibitors is
acceptable. Clinical improvement occurs with this treatment in most instances (23).
PFAPA
A recently described syndrome of periodic fever (up to 40.5C), aphthous stomatitis,
pharyngitis, and cervical adenitis (PFAPA) has been described. These patients are
children around the age of 3 years who present with 5-day long episodes of the defining
symptoms occurring about every 28 days. The cause of PFAPA is unknown, and the
disease has no long-term sequelae. Glucocorticoids effectively control symptoms, and
tonsillectomy and cimetidine may lead to remission. The patients are asymptomatic
between episodes. Cyclic neutropenia must be excluded (24).
Idiopathic Pharyngitis
The clinician usually can determine most causes of pharyngitis, especially if proper
histories and careful physical examinations are done, with cultures and biopsies
performed when indicated; however, some patients present with pharyngeal pain without
an obvious explanation. Clinicians then must look closely at possible predisposing
factors, such as postnasal drainage affecting the pharynx (e.g., subclinical
rhinopharyngitis) or reflux of gastric juices causing a peptic esophagitis, laryngitis, or
pharyngitis (23). Dietary and personal habits also may play a role, especially because
tobacco or alcohol abuse can cause persistent symptoms, and acidic liquids, or hot, spicy,
or scratchy foods can prolong or worsen symptoms. Hot soups or tea may be useful
psychologically in patients with pharyngitis, but they can cause thermal burns of already
inflamed tissues.
Certain medications also can irritate the throat, including commercial mouth washes and
throat sprays containing astringents and disinfectants. Some of these preparations contain
phenol, alcohol, or acids that can chemically burn a sensitive throat. Even saline solutions
can irritate an inflamed throat if the solution is too hypertonic. Thermal injury to the
pharynx also may result from the use of crack or free-base cocaine (25). Factitious or
self-induced causes of pharyngitis (i.e., Munchausen syndrome) also must be considered,
especially in persons with known emotional or psychiatric disturbances. These cases can
be difficult to diagnose and treat, and they mandate the careful dispensing of empiric or
symptomatic medications. Appropriate consultations can help minimize errors in clinical
judgment.
ACKNOWLEDGMENT
We thank Pamela A. Thompson for her conscientious research assistance.

HIGHLIGHTS
Pharyngitis is one of the most common disorders affecting the
head and neck.
Causes of pharyngitis include infection, inflammation,
congenital disorders, and neoplasms.
Diagnosis of pharyngitis is based on a careful history and
physical examination.
Aerobic and anaerobic bacterial cultures may be required to
establish a diagnosis of bacterial infection.
Viral cultures are uncommonly justified in managing patients
with pharyngitis.
Mycoses are uncommon causes of pharyngitis and require
special stains and cultures for diagnosis.
Granulomatous inflammation may result from infectious agents,
systemic diseases (Wegener granulomatosis), foreign material,
or neoplasms. All etiologies should be constructively excluded.
Persistent symptoms of pharyngitis may result from postnasal
drainage or reflux esophagitis.
Effective treatment of any pharyngeal lesion requires
establishing a correct diagnosis.
Failure of a pharyngeal lesion to resolve with empiric therapies
requires appropriate cultures or biopsy.
Major complications of pharyngitis include uncontrolled sepsis,
hemorrhage, or airway obstruction.
CHAPTER REFERENCES
1. Bisno AL, Gerber MA, Gwaltney JM, et al. Diagnosis and management of group A streptococcal
pharyngitis: a practice guideline. Clin Infect Dis 1997;25:574583.
2. Gerber MA, Tanz RR, Kabat W, et al. Optical immunoassay test for group A -hemolytic
streptococcal pharyngitis. An office based, multicenter investigation. JAMA 1997;277:899903.
3. El-Dahar NT, Hajazi SS, Rawashdeh NM, et al. Immediate vs delayed treatment of group A beta-
hemolytic streptococcal pharyngitis with penicillin V. Pediatr Infect Dis J 1991;10:126130.
4. Pichichero ME, Hoeger W, Marsocci SM, et al. Variables influencing penicillin treatment
outcome in streptococcal tonsillopharyngitis. Arch Pediatr Adolesc Med 1999;153:565570.
5. Tsevat J, Kotagal UR. Management of sore throats in children. A cost-effectiveness analysis. Arch
Pediatr Adolesc Med 1999;153:681688.
6. Brook I, Gober AE. Role of bacterial interference and beta-lactamaseproducing bacteria in the
failure of penicillin to eradicate group A streptococcal pharyngotonsillitis. Arch Otolaryngol Head
Neck Surg 1995;121:14051409.
7. Dajani AS, Ayoub E, Bierman FZ, et al. Guidelines for the diagnosis of rheumatic fever: Jones
criteria updated 1992. JAMA 1991;268:20692073.
8. Dajani AS, Taubert K, Ferrieri P, et al. Treatment of acute streptococcal pharyngitis and
prevention of rheumatic fever: a statement for health professionals. Pediatrics 1995;96:758764.
9. Galazka AM, Robertson SE. Diphtheria: changing patterns in the developing world and the
industrialized world. Eur J Epidemiol 1995;11:107.
10. Feigin RD, Cherry JD. Pertussis. In: Feigin RD, Cherry JD, eds. Textbook of pediatric infectious
diseases. Philadelphia: WB Saunders, 1992:1208.
11. Xu W, Sundqvist VA, Brytting M, et al. Diagnosis of cytomegalovirus infections using
polymerase chain reaction, virus isolation and serology. Scand J Infect Dis 1993;25:311.
12. Wenig BM, Thompson LDR, Frankel SS, et al. Lymphoid changes of the nasopharyngeal and
palatine tonsils that are indicative of human immunodeficiency virus infection: a clinicopathologic
study of 12 cases. Am J Surg Pathol 1996;20:572.
13. Schuma P, Capps L, Peng G, et al. Weekly fluconazole for the prevention of mucosal candidiasis
in women with HIV infection. A randomized, double-blind, placebo-controlled trial. Ann Intern
Med 1997;126:689696.
14. Waldman RH. Tuberculosis and the atypical mycobacteria. Otolaryngol Clin North Am
1982;15:581.
15. Brazin SA. Leprosy (Hansen's disease). Otolaryngol Clin North Am 1982;15:597.
16. Wolkenstein P, Revuz J. Drug-induced severe skin reactions. Incidence, management and
prevention. Drug Saf 1995;13:56.
17. Amagai M. Pemphigus autoimmunity to epidermal cell adhesion molecules. Adv Dermatol
1996;11:319.
18. Huilgol SC, Black MM. Management of the immunobullous disorders II. Pemphigus. Clin Exp
Dermatol 1995;20:283293.
19. Axt M, Wever S, Baier G, et al. Cicatricial pemphigoid: a therapeutic problem. Hautarzt
1995;46:620.
20. Lilly JP, Spivey JD, Fotos PG. Benign mucous membrane pemphigoid with advanced periodontal
involvement: diagnosis and therapy. J Periodontol 1995;66:737.
21. Eversole LR. Inflammatory diseases of the mucous membranes. Part 2. Immunopathologic
ulcerative and desquamative diseases. J Calif Dent Assoc 1994;22:59.
22. Lin AN. Management of patients with epidermolysis bullosa. Dermatol Clin 1996;14:381.
23. Rival R, Wong R, Mendelsohn M, et al. Role of gastroesophageal reflux disease in patients with
cervical symptoms. Otolaryngol Head Neck Surg 1995;113:335.
24. Thomas KT, Feder HM, Lawton AR, et al. Periodic fever syndrome in children. J Pediatr
1999;135:1521.
25. Meleca RJ, Burgio DL, Carr RM, et al. Mucosal injuries of the upper aerodigestive tract after
smoking crack or freebase cocaine. Laryngoscope 1997;107:620625.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

48 ODONTOGENIC INFECTIONS
Head & Neck SurgeryOtolaryngology
48




ODONTOGENIC INFECTIONS
WILLIAM LAWSON
ANTHONY J. REINO

W. Lawson and A.J. Reino: Department of OtolaryngologyHead and Neck
Surgery, Mount Sinai Medical Center, New York, New York.


Localized Infections
Regional (Fascial Space) Infections
Canine Space
Buccal Space
Sublingual Space
Submandibular Space
Submental Space
Ludwig Angina
Masticator Space
Parapharyngeal Space
Retropharyngeal Space
Treatment of Dental Infections
Other Infections
Dental-Sinus-Orbital Infections
Osteomyelitis
Actinomycosis
Septicemia
Chapter References
Dental infections arise from pulpal and periodontally involved teeth. The former tend to
be more aggressive, with the necrotic contents of a nonvital tooth extending through the
apical foramen of the root into the surrounding alveolar bone. The fate of the infection
then depends on the virulence of the bacteria, host-resistant factors, and regional
anatomy. Odontogenic infections may arise from an in situ infected tooth or after
extraction of a tooth. In the latter instance, infection may occur despite the oral
administration of antibiotics. The interval for the development of the infection may be
less than 1 day to as long as 1 to 3 weeks.
The resultant infectious processes can be broadly divided by location into those localized
to the dentoalveolar process; those that extend along fascial planes to various regions of
the face, neck, and beyond; and those with systemic dissemination by the development of
a bacteremia. Other subgroupings are by clinical features (e.g., necrotizing and gas-
forming infections), bone involvement (e.g., osteomyelitis), and unusual organisms (e.g.,
actinomycosis).
LOCALIZED INFECTIONS
Pulpally involved teeth clinically demonstrate percussion tenderness, increased pain to
heat, and a diminished or absent response to electrical vitality testing. Initially, there may
be no evidence of osseous change on radiographic examination. Later, widening of the
periodontal membrane space surrounding the tooth may develop as well as rarefaction of
the periapical bone. With an indolent infection, a condensing osteitis in the bone about
the root apex may occur. A radicular cyst may form gradually after months or years as a
result of inflammation-induced proliferation of epithelial rests present in the periodontal
membrane or suspensory ligament of the tooth (Fig. 48.1). It should be noted that the
severity of the infection, that is, whether it remains localized to the alveolus, forms a deep
space infection, or becomes disseminated, does not correlate with the extent of the
radiographic findings.

FIGURE 48.1. Surgical exposure of a radicular cyst
arising from carious maxillary incisor teeth.



The infection may remain localized within the medullary space of the mandible or
maxilla, or it may perforate the cortical plates to become extraosseous. After the infection
is in the soft tissues, it may take the form of a diffuse cellulitis or a walled-off abscess
cavity involving the labial or buccal gingiva parulis and alveolar mucosa to form a
vestibular space infection (Fig. 48.2). Anteriorly, it may cause enlargement of the lip
(macrocheilia), which may be mistaken for angioneurotic edema if the infectious nature
of the process is not recognized (Fig. 48.3). Localized dental pain and referred pain are
present when the pulpal necrotic contents are under pressure and when the periosteum
over the bone is being elevated or perforated; however, it may subside or completely
disappear when the soft tissue component of the infection occurs.

FIGURE 48.2. Vestibular abscess (arrows) developing
from carious maxillary anterior teeth.



FIGURE 48.3. Lip cellulitis in a child secondary to a
fractured maxillary incisor tooth with pulpal exposure.



In the maxilla, the root ends are close to the labial and buccal plates. This positioning,
combined with a thick block of alveolar bone interposed between the root ends and the
hard palate, almost always produces extension buccally. Moreover, the dense attachment
of the palatal mucosa to the underlying bone limits the spread of infection in cases that
burrow medially, producing a localized, tender, unilateral palatal mass. Occasionally, the
abscess is nontender and simulates a neoplasm. In the mandible, the dental roots are
closer to the lingual cortex posteriorly, and extraosseous spread may involve the floor of
the mouth; however, in most cases, infections of both anterior and posterior mandibular
teeth tend to spread buccally.
In some cases, the infectious process perforates the overlying mucosa to form a fistula,
generally intraoral at the apex of the root of the affected tooth. Infrequently, it may drain
through the facial skin to produce a dentocutaneous fistula (Fig. 48.4). Failure to
recognize the dental etiology of this lesion may lead to the misdiagnosis of an infected
sebaceous cyst. Resection of the fistulous tract usually leads to its prompt reformation.
Rarely, an infected maxillary incisor undergoes fistulization into the floor of the nasal
cavity, producing a lesion mistaken for a nasal vestibular abscess or infected cyst.

FIGURE 48.4. Dentocutaneous fistula
extending from the roots of a nonvital
mandibular molar tooth to the facial
skin.



Periodontal infections generally remain localized to the alveolus. The abscess cavity that
forms tends to involve the gingiva of the affected tooth, which becomes loose and tender
and is bathed by purulent secretions. In children, pulpally infected teeth with partially
resorbed roots may present similarly. Infection of the gingival covering of a partial
erupted third molar operculum produces the condition termed pericoronitis. In addition to
local pain, trismus is often present. Virulent, neglected, or inadequately treated infections
at this site may lead to involvement of the masticator, peritonsillar, and deep pharyngeal
spaces. Chronic indolent infections may manifest themselves by producing upper cervical
lymphadenopathy, which may be mistaken for a neoplastic process.
REGIONAL (FASCIAL SPACE) INFECTIONS
The fascial layers of the head and neck represent condensed sheaths of connective tissue
that surround muscles and produce planes that present potential spaces for the spread of
infections.
The superficial cervical fascia is an indistinct connective tissue layer between the skin
and deep fascia that contains fat, lymphatic vessels and nodes, blood vessels, and nerves.
In the neck, it contains the platysma muscle. Only posteriorly in the neck is it attached by
an aponeurosis to the sternomastoid and trape-zius muscles and the superior nuchal line.
The deep cervical fascia consists of three parts. The superficial layer of the deep
investing fascia envelops the trapezius, sternocleidomastoid, and strap muscles as well as
the parotid and submandibular glands. In the upper neck, it extends from the hyoid bone
superiorly to the anterior border of the sternomastoid muscle and then over the mandible
to the zygomatic arch. It divides to attach to the outer and inner aspects of the mandible,
to encapsulate the submaxillary gland, to invest the muscles of mastication, and then to
enclose the parotid gland. The middle layer invests the visceral organs (e.g., trachea,
larynx, esophagus, thyroid gland), and the deep layer envelops the cervical vertebrae. The
carotid sheath sits between all three layers.
Canine Space
The levator of the upper lip (quadratus labii superioris) originates from the face of the
maxilla by several heads to insert into the angle of the mouth. Medially, a potential space
exists between the infraorbital and zygomatic heads as well as between it and the caninus
muscle arising from the bone above the canine fossa. This represents a plane along which
an infection from the cuspid tooth can track superiorly. Clinically, a firm or fluctuant
mass appears along the lateral border of the nose adjacent to the medial canthus of the
eye. Treatment is by dependent drainage intraorally or percutaneously if the abscess is
pointing there. As with all infections from pulpally involved teeth, extraction or root
canal therapy is also necessary.
Buccal Space
This space is bounded by the buccinator muscle and
buccopharyngeal fascia medially, the cheek skin laterally,
the lip muscles anteriorly, the pterygomandibular raphe
posteriorly, the zygomatic arch superiorly, and the lower
aspect of the mandible inferiorly. Infections of maxillary
and mandibular bicuspid and molar teeth have access to this
space when their necrotic pulpal contents extend through
the buccal cortical plates above or below the attachments
of the buccinator muscle on the alveolar processes,
respectively (Fig. 48.5). Extension of the dental infection
beneath the buccinator origin insertion leads to the intra-
oral formation of a vestibular abscess.

FIGURE 48.5. Buccal space infection
with periorbital extension developing
from a nonvital maxillary molar tooth.



Clinically, the buccal space infection produces a tender swelling of the cheek, which
extends medially to the middle of the upper lip, where it is stopped by the fibers of the
orbicularis oris muscle that form the philtrum and involves one third of the lower lip to
where the fibers of the depressor anguli oris run from the skin to the oral mucosa.
Posteriorly, it extends over the ramus of the mandible to the border of the parotid gland.
Superiorly, it may close the eye entirely by producing circumferential eyelid edema;
however, the orbital contents are protected because the infection remains superficial to
the orbital septum and tarsal plates of the eyelids.
In all cases of periorbital infection producing eye closure, the eyelids must be forced
open to determine whether a postseptal component is present that is placing the orbital
contents at risk. Generally, no intraoral component to this infection is present. Treatment
is by percutaneous drainage because the plane of the infection is beneath the skin.
In the preantibiotic era, mid-facial infections were considered potentially life threatening
because septic thrombophlebitis of the angular blood vessels represented a pathway of
intracranial extension into the cavernous sinus. Cavernous sinus thrombo-sis from
infections of dental origin is essentially a curiosity at present.
Sublingual Space
The sublingual space is bounded anteriorly and laterally by the mandible, superiorly by
the floor of mouth and tongue, inferiorly by the mylohyoid muscle, posteriorly by the
hyoid bone, and medially by the genioglossus, geniohyoid, and styloglossus muscles.
This lingual space communicates freely with that of the opposite side because there is no
true fascial separation between them. The sublingual space also communicates anteriorly
with the submental space below through dehiscences in the mylohyoid muscle and raphe.
The mylohyoid ridge to which the muscle attaches to the inner aspect of the mandible
slopes downward anteriorly; consequently, infections from the anterior teeth as well as
the bicuspids and first molar tooth remain above the mylohyoid shelf into the sublingual
space. Early infections produce unilateral elevation of the floor of the mouth adjacent to
the offending tooth. Advanced infections spread anteriorly beyond the midline to the
opposite side and posteriorly to produce elevation of the base of the tongue. Treatment is
by intraoral drainage.
Submandibular Space
The submandibular space is separated superiorly from the sublingual space by the
mylohyoid, hyoglossus, and styloglossus muscles medially and by the body of the
mandible laterally. The lateral border is the overlying skin, superficial fascia, platysma
muscle, and the superficial layer of the deep cervical fascia. Its inferior boundary is
formed by the anterior and posterior bellies of the digastric muscle. Anteriorly, the space
communicates freely with the submental space and posteriorly with the pharyngeal space.
The contents of this space are the submaxillary gland, Wharton duct, the lingual and
hypoglossal nerves, the facial artery, and some lymph nodes and fat.
Involvement of the submandibular space is produced
principally by infections of the second and third
mandibular molar teeth because of the higher position of
the mylohyoid ridge on the mandible posteriorly, which
places their root apices beneath the mylohyoid muscle.
Clinically, a tense, ill-defined swelling is generally
present below the mandible, which makes palpation of its
inferior border difficult (Fig. 48.6). Management is by an
external cervical incision placed beneath the mandibular
nerve to avoid injury to it and to provide adequate
dependent drainage.

FIGURE 48.6. Submandibular space
abscess from a pulpally involved
mandibular molar tooth. The swelling
over the mandible is ill defined and
prevents palpation of its inferior
border.



Submental Space
The submental space is a triangular space positioned in the midline beneath the mandible
with the symphysis as its superior border and its lateral margins the anterior bellies of the
digastric muscle. The floor of the space is the mylohyoid muscles, and the roof is the
overlying skin, superficial fascia, and platysma muscle. Its contents are a few scattered
lymph nodes and fibrofatty tissue. Its source of infection is by drainage from the
mandibular incisor teeth as well as their gingiva and the central portion of the lower lip.
Entry into the space also can occur from an infection in the adjacent sublingual and
submandibular spaces. Infrequently, a posterior mandibular tooth may produce infection
in the space without involvement of the adjacent submandibular space. Clinically, a firm,
tense swelling is present beneath the chin. Management is by a small upper cervical
incision placed in the midline to gain dependent drainage of the contents of the space.
Ludwig Angina
The term Ludwig angina refers to the collective involvement of the submandibular and
sublingual spaces bilaterally and the submental space (1). Cases of dental origin arise
from infections of the mandibular molar teeth, with the bicuspids rarely the source. The
rapid spread of infection from one space to another demonstrates the facility with which
virulent organisms can move through the compartments of the head and neck.
Clinically, a collar of brawny edema extends across the
entire upper anterolateral neck with elevation of the floor
of the mouth (Fig. 48.7). As the sublingual spaces become
progressively more involved, the tongue becomes posteriorly
displaced with kinking of the supraglottic area producing
airway obstruction. The causative organisms include a
variety of aerobic and anaerobic gram-positive cocci and
gram-negative rods. Not infrequently, a mixed microbial
flora is isolated.

FIGURE 48.7. Ludwig angina. Note cuff
of bilateral submandibular and
submental swelling enveloping upper
neck and elevation of the floor of the
mouth, causing protrusion of the
tongue.



After the diagnosis of Ludwig angina is made, the first priority is maintenance of the
airway through an elective tracheotomy with the patient under local anesthesia. One
should not wait for dyspnea or cyanosis to develop because these are later signs and
signal impending airway closure. Attempts at oral and blind nasal intubation are fraught
with difficulty because of the anatomic distortion of the supraglottis and may precipitate
sudden total airway obstruction.
In recent years, a strong case has been made for observation of these patients in an
intensive care unit setting with a pulse oximeter (1). Another option to be considered is
nasotracheal fiberoptic intubation as an alternative to tracheotomy (2). Blind nasotracheal
intubation is not advisable, and routine orotracheal intubation is rarely applicable (3). The
bottom line is that the airway must be protected by the most appropriate method in each
circumstance, and if the setting for observation or the skill and experience of the
intubating physician is not optimal, there should be no reluctance to proceed to
tracheotomy.
Although this infection is characterized as a brawny cellulitis, in some cases pockets of
suppuration develop that require drainage through an external cervical approach. Intraoral
drainage carries the risk of aspiration in patients with severe edema of the oral cavity and
oropharynx. Systemic antibiotic therapy is not a substitute for tracheostomy except in
early cases with minimal floor of the mouth swelling, which can be continuously
observed. After massive edema has developed, it may take 1 week or more for it to
subside with antibiotic therapy; therefore, control of the airway by tracheostomy is
essential.
Masticator Space
Whereas the anterior layer of deep cervical fascia invests the muscles of mastication,
connective tissue subdivisions create separate masseteric, temporal, and pterygoid spaces,
all of which freely intercommunicate. The masseteric compartment is bound by the
masseter muscle laterally and the ramus of the mandible medially. The pterygoid
compartment has the pterygoid muscles medially and the mandibular ramus laterally as
its borders. The temporal compartment itself is subdivided into two portions. The
superficial portion is between the superficial temporal fascia and the temporalis muscle;
and the deep portion is between this muscle and the periosteum of the temporal bone. The
greatest space is present between the pterygoid and temporal compartments. Anteriorly,
the space is bound by the pterygomandibular raphe and posteriorly its connective tissue
envelops the parotid gland to form the combined parotidomasseteric fascia. In addition to
the muscles of mastication, the masticator space contains fibrofatty tissue, the internal
maxillary artery, and the mandibular nerve.
Infections of the masticator space tend to involve all the muscles. The hallmark is severe
trismus with minimal external swelling. Fullness over the ramus of the mandible may be
pres-ent from external displacement of the masseter muscle, or swelling may be present
about the zygomatic arch from extension into the infratemporal space. More prominent
facial swelling is seen with involvement of the temporal space. Intra-oral palpation along
the ramus of the mandible or behind the maxillary tuberosity may elicit fullness,
tenderness, and fluctuance. The source of infection of this space is from maxillary and
mandibular molar teeth. Confirmation of the diagnosis is by computed tomography (CT),
which delineates the muscles and fascial planes exceedingly well. Management is by
surgical drainage intraorally. With large abscesses that extend toward the lateral
pharyngeal space, external drainage is necessary. The major difficulty in treating these
cases is in establishing the airway for the induction of general anesthesia, which may be
accomplished by awake nasoendotracheal intubation but often requires preliminary
tracheotomy under local anesthesia.
Parapharyngeal Space
The parapharyngeal (also called pharyngomaxillary or lateral pharyngeal) space is cone
shaped, with its apex below at the lesser cornua of the hyoid bone. It is bound medially
by the pharynx and laterally by the ascending ramus of the mandible, the pterygoid
muscles, and the capsule of the parotid gland. Superiorly, it extends to the skull base.
Inferiorly, it extends to about the level of the hyoid bone, where it is interrupted by the
fascia of the submandibular gland, the stylohyoid muscle, and the posterior belly of the
digastric muscle. The space is divided into prestyloid and poststyloid compartments. The
prestyloid compartment contains the internal maxillary artery and the inferior alveolar,
lingual, and auriculotemporal nerves. The posterior wall is the carotid sheath. The
poststyloid compartment is traversed by the internal jugular vein, the carotid artery,
cranial nerves IX, X, and XI, and cervical sympathetic nerves.
Clinically, the patient with a parapharyngeal space abscess
presents with an intraoral bulge of the tonsil and lateral
pharyngeal wall and external swelling of the soft tissues
over the mandible and the parotid region (Fig. 48.8).
Symptoms include pharyngeal pain, dysphagic muffled voice,
trismus, and fever. Purulence in the posterior compartment
produces fewer and less focal findings. CT scanning can
demonstrate whether cellulitis, an abscess cavity, or
enlarged lymph nodes are present (Fig. 48.9).

FIGURE 48.8. Intraoral view of a
parapharyngeal space infection
revealing massive pharyngeal edema
with displacement of the tonsil toward
the midline.



FIGURE 48.9. Axial computed tomography
scan of a parapharyngeal space
infection. The upper airway is
encroached upon by swelling of the
lateral pharyngeal soft tissues, with
a central lucency (arrows)
representing the abscess cavity.



Patients with deep neck infections are hospitalized for observation of the airway, the
administration of intravenous antibiotics, and fluid replacement. Only a few patients with
cellulitis resolve on conservative therapy, with most requiring surgical drainage.
Tracheostomy may be necessary when signs of airway obstruction develop and when
trismus makes oral intubation impossible. Surgical exploration and drainage should be
performed when a patient does not improve within 24 hours or deteriorates while under
observation. The parapharyngeal space is drained by a lateral cervical incision, following
the posterior belly of the digastric and stylohyoid muscles into its center.
The complications of parapharyngeal space infections are associated with the structures
that run through or adjacent to it. These include hoarseness or aspiration related to vagal
injury, Horner syndrome related to sympathetic nerve injury, ster-nocleidomastoid or
trapezius weakness from accessory nerve injury, decreased pharyngeal sensation related
to glossopharyngeal nerve injury, and tongue paresis from hypoglossal nerve injury.
Infrequently, direct injury to the cervical spine, including erosion and atlantoaxial
subluxation, develops.
Infection adjacent to the internal jugular vein may induce
septic thrombophlebitis with spiking fevers, engorged optic
disks, and possibly elevated cerebrospinal fluid (CSF)
pressure. In these cases, not only should the
parapharyngeal space be drained, but the thrombophlebitis
section of the internal jugular should be ligated and the
infected part excised. One of the most dreaded
complications is the development of a mycotic aneurysm of
the carotid artery from erosion of its wall by the purulent
material present within its sheath (Fig. 48.10).
Unfortunately, in about 75% of cases, the aneurysm involves
the common or internal carotid artery. If time allows,
arteriography will identify which segment is involved, and
balloon occlusion helps to determine the risk of stroke.
The eroded segment of artery requires ligation to prevent a
catastrophic event.

FIGURE 48.10. Angiogram of a patient
with a neglected parapharyngeal space
abscess revealing a mycotic aneurysm
of the carotid artery.



Retropharyngeal Space
The retropharyngeal space is sandwiched between the pharyngeal constrictor muscles and
the alar layer of the prevertebral fascia. It extends from the skull base at the pharyngeal
tubercle downward behind the pharynx and esophagus, communicates with the
pretracheal space, and ends in the mediastinum at about the level of the carina.
Consequently, suppuration in this space may drain into either the anterior or posterior
mediastinal compartments. This space has been thought of as the highway to the
mediastinum. The space contains the retropharyngeal lymphatics, which drain the
posterior two thirds of the nose, the nasopharynx, the paranasal sinuses, the soft palate,
and the eustachian tube.
Directly behind the retropharyngeal space is the danger space, which leads into the
posterior mediastinum, and behind it the prevertebral space, which extends to the sacrum.
These spaces all intercommunicate (including the parapharyngeal and paramandibular)
and carry the potential for distant spread of an infection.
As with infections of the lateral pharyngeal space, the
most common dental source is carious or periodontal
(pericoronitis) involvement of the mandibular third molar.
The spread of infection into the deep neck spaces often
causes pain and limitation of jaw or neck motion. Diffuse
swelling with pitting edema of the neck may be present;
however, fluctuance is a rare physical finding. Infection
of the retropharyngeal space may cause dysphagia,
odynophagia, drooling, and aspiration. Patients also may
have dyspnea and stridor, with a hot potato voice.
Examination of the pharynx usually shows fullness and
erythema of the posterior pharyngeal wall, often with a
central furrow produced by the midline raphe (4). Patients
with deep neck infections are usually toxic with spiking
fevers. A lateral radiograph of the neck reveals marked
thickening of the prevertebral soft tissues in the involved
segment (Fig. 48.11). The CT scan reveals the position and
dimensions of the abscess cavity (Fig. 48.12).

FIGURE 48.11. Lateral neck radiograph
of a retropharyngeal space abscess.
Massive prevertebral soft tissue
swelling is present from the skull
base to the superior mediastinum, with
displacement of the trachea forward.
Note straightening of the cervical
spine.



FIGURE 48.12. Axial computed
tomography scan of a retropharyngeal
space abscess (arrows) that has
remained paramedian because of the
midline raphe.



The retropharyngeal space is best drained from an external approach. Intraoral drainage
carries the risk of pulmonary complications from aspiration. The use of intravenous
antibiotics is mandatory.
The retropharyngeal abscess may be complicated by
spontaneous rupture into the pharynx, with the aspiration
of pus producing pneumonia and possibly a lung abscess. The
abscess also may dissect into the mediastinum, with the
patient developing relief of throat pain and onset of
shortness of breath, chest pain, and tachycardia.
Mediastinitis carries a 30% to 50% mortality rate and
requires immediate drainage of the mediastinum (Table
48.1). Delayed diagnosis and inadequate surgical drainage
are the primary causes of lethal descending mediastinitis.
CT of the chest is a valuable tool for early diagnosis, and
its routine use in all patients with deep neck abscesses
has been advocated.

TABLE 48.1. DIAGNOSIS ODONTOGENIC
INFECTIONS



TREATMENT OF DENTAL INFECTIONS
The initial treatment of dental infections includes appropriate antibiotic therapy and
surgical drainage of abscesses. After the offending tooth is identified, it may be extracted
or root canal therapy may be performed, depending on its salvageability.
The choice of antibiotic therapy is related to several factors, including the nature of the
oral flora, the state of the host (e.g., debilitated, chronic systemic disease,
immunocompromised), and the clinical features of the infection (e.g., localized, deep
space, presence of gas, necrotizing fasciitis).
Most dental infections contain a mixed flora of aerobic and anaerobic bacteria. Common
organisms against which antibiotic coverage must be directed are aerobic streptococci
and anaerobes such as Bacteroides (especially B. melaninogenicus). Occasionally, lower
intestinal flora such as B. fragilis and gram-negative rods are isolated.
Penicillin has traditionally been the antibiotic used to
treat dental infections because it is effective against
both aerobic and anaerobic bacteria indigenous to the oral
cavity; however, the increasing role of -lactamase
producing organisms, as well as gram-negative rods in head
and neck infections, led to the use of agents providing a
broader range of antimicrobial coverage. In cases in which
oral administration is deemed adequate, clavulanic
acid/amoxicillin (Augmentin) is used in penicillin-non-
allergic patients and clindamycin or ciprofloxacin in those
with penicillin sensitivity. If parenteral use is required,
ampicillin/sulbactam (Unasyn) can be given intravenously to
penicillin-nonallergic patients, with clindamycin and
ciprofloxacin used in penicillin-allergic patients (Table
48.2).

TABLE 48.2. TREATMENT ODONTOGENIC
INFECTIONS



OTHER INFECTIONS
Bacterial soft tissue infections may be classified into (a) clostridial anaerobic cellulitis,
(b) nonclostridial anaerobic cellulitis, (c) necrotizing fasciitis, and (d) synergistic
necrotizing cellulitis (5). In clostridial and nonclostridial anaerobic cellulitis, superficial
necrosis and gas formation occur from anaerobic spore-forming and nonspore-forming
organisms, respectively. In necrotizing fasciitis, severe gangrene of the skin and
superficial and deep fascia occur, occasionally with the production of gas, by
staphylococci, hemolytic streptococci, and gram-negative rods. Synergistic necrotizing
cellulitis is a variant in which myonecrosis also develops, which is produced by the
interaction of anaerobic and gram-negative bacteria.
Most necrotizing infections follow massive trauma associated with fracture of the
mandible, but may arise from an isolated dental infection. A case of synergistic
necrotizing fasciitis developing 3 weeks after dental extraction in a normal host was
described by Krespi and colleagues (5).
Patients with severe necrotizing and gas-forming infections
of the head and neck are generally critically ill, with
extensive involvement of multiple spaces. The disease
process progresses rapidly, with the overlying skin
changing from discolored to frankly gangrenous and with
liquefaction and crepitation of the subcutaneous tissues
(Fig. 48.13). Extension into the mediastinum is not
unusual. In these severe necrotizing infections, systemic
symptoms are common, with fever, toxicity, malaise,
confusion, weakness, hypotension, and tachycardia
prevalent.

FIGURE 48.13. Synergistic necrotizing
fasciitis of the posterolateral neck
developing after extraction of a
mandibular molar tooth.



Radiographic studies often reveal subcutaneous emphysema as
well as the presence of gas and pockets of suppuration in
the deep tissues and visceral spaces (Fig. 48.14). CT scans
also reveal obliteration of the soft tissue planes of the
involved segments of the neck.

FIGURE 48.14. Gas-forming odontogenic
infection. Axial computed tomography
scan reveals the presence of
subcutaneous air (arrows) and
effacement of the soft tissue planes
of the neck.



Clinically, it is impossible to differentiate clostridial from nonclostridial infections. Also,
these infections tend to be polymicrobial, with a destructive synergistic interplay between
the causative organisms. Consequently, Gram stains should be made from the necrotic
tissues, or aspirates, to determine the nature of the infection. The presence of gram-
positive, spore-forming rods signifies the presence of Clostridium, whereas gram-positive
cocci and gram-negative rods suggest a synergistic necrotizing infection. Aerobic and
anaerobic cultures are necessary for the correct identification of the causative organisms.
A variety of organisms have been identified as causative agents of necrotizing and gas-
forming infections. Among the anaerobes isolated are Bacteroides, Fusobacterium,
Propionibacterium, Peptostreptococcus, and Eubacterium. The gram-negative bacteria
implicated involve most of the coliform bacilli, including Proteus, Klebsiella,
Enterobacter, and Pseudomonas. Therapy must be aggressive, with fasciotomy and
radical debridement necessary, in addition to intravenous antibiotics. Antimicrobial
therapy must cover both gram-positive and gram-negative aerobic and anaerobic bacteria.
We favor management with intravenous clindamycin and a later-generation cephalo-
sporin such as ceftazidime (or Aztreonam).
Recently, Langford et al. (6) reported their experience with the use of adjunctive
hyperbaric oxygen therapy in six patients with cervical necrotizing fasciitis. In this study,
there were no mortalities, and the authors' conclusion was that hyperbaric oxygen therapy
should be considered in the treatment regimen of cervical necrotizing fasciitis after
initiation of intravenous antibiotic and surgical debridement.
DENTAL-SINUS-ORBITAL INFECTIONS
Both superficial, or preseptal (periorbital cellulitis), and deep, or postseptal (orbital
cellulitis, subperiosteal abscess, orbital abscess, retrobulbar abscess), infections can occur
from a dental focus of infection. Odontogenic infections can spread to the orbit via
several routes. Infection from the maxillary premolar and molar teeth may perforate the
maxillary buccal plate and spread posteriorly into the pterygopalatine and infratemporal
fossas. They then may gain orbital access through the infraorbital fissure or perforate the
posterior maxillary wall to enter the maxillary sinus. Orbital involvement also may occur
indirectly by lymphatic invasion. The anterior teeth of the maxillary alveolus may
produce orbital cellulitis by retrograde spread through the valveless anterior facial,
angular, and ophthalmic veins. Other potential pathways from the dentition to the orbit
include traumatic and congenital dehiscences of the orbital floor.
The sequence of events in these cases is that a pulpally involved maxillary premolar or
molar tooth drains its necrotic contents into the maxillary sinus. From the antrum, the
infection extends superiorly and medially into the ethmoid labyrinth and enters the orbit
through the lamina papyracea. Preseptal infections are characterized by periorbital
edema, without evidence of ocular involvement. Management is by systemic antibiotic
therapy. Postseptal infections produce proptosis, chemosis, and ophthalmoplegia
(superior orbital fissure syndrome). This condition carries the risk of blindness from
increased intraocular pressure, which causes thrombosis of the retinal artery, and of
regional sepsis producing optic neuritis. Surgery is performed on an emergency basis,
both for drainage of the infection and for preservation of vision, and entails an external
ethmoidectomy and orbital decompression in conjunction with an antrostomy of the
involved maxillary sinus. Whenever a sinogenic orbital infection develops, the patient
should be carefully questioned about antecedent toothache or dental instrumentation.
Intravenous antibiotic therapy is administered for 5 to 7 days, depending on the clinical
course, followed by 2 weeks of oral antibiotics to minimize the incidence of relapse.
Osteomyelitis
Osteomyelitis is an infection within the medullary portion of the bone and may result
from an acute or chronic odontogenic infection. The mandible is involved more often
than the maxilla. Predisposing factors to the formation of osteomyelitis are regional
radiotherapy, trauma (mechanical or electrical), systemic disease (diabetes),
osteodystrophies (Paget disease, osteopetrosis), endosteal lesions (cementomas), the
insertion of dental implants, and the immunocompromised state (leukemia, chronic
steroid therapy, chemotherapy, acquired immunodeficiency syndrome). A knowledge of
the presence of one of these conditions may facilitate the diagnosis of osteomyelitis in a
patient with a chronic facial pain syndrome.
Establishing the diagnosis of osteomyelitis by imaging techniques involves the use of CT
scanning and radionuclide studies. The demonstration of bone destruction by CT
scanning is highly diagnostic. Bone scanning may reveal increased activity at the
suspected site earlier, but it is less specific because soft tissue inflammation and recent
surgery may give a false-positive test result. More recently, positron emission
tomography using radioisotopes of physiologically active compounds such as glucose,
ammonia, and fluoride has shown greater promise in mapping out varying margins of
metabolic activity (Hudson).
Acute suppurative osteomyelitis may follow a periapical infection, but is rare except in
immunocompromised persons. Clinically, pain, fever, and often cervical
lymphadenopathy generally are present. Radiographically, rarefaction may not develop
for 1 to several weeks. In chronic osteomyelitis resulting from an indolent or
inadequately treated dental infection, the primary complaint is pain. Radiographically, an
irregular lytic lesion is present, occasionally in association with a sequestrum of
nonviable bone.
The organisms most commonly isolated in cases of osteomyelitis of the maxilla and
mandible are Staphylococcus aureus and hemolytic streptococci; however, cases
produced by gram-negative bacteria have been reported. Even rarer causes are
tuberculosis, syphilis, Coccidioides, and Klebsiella.
The guidelines for the treatment of acute or chronic osteomyelitis are as follows: (a)
beginning appropriate antibiotics based on culture and sensitivity (we favor the use of
clindamycin and ceftazidime initially for 3 weeks intravenously, followed by 6 weeks of
oral administration); (b) disrupting the infectious foci by debridement of foreign bodies,
sequestra, or necrotic tissue; (c) considering adjunctive treatments to enhance
microvascular reperfusion (trephination, decortication, vascular flaps, hyperbaric oxygen
therapy); and (d) reconstruction as necessary following the resolution of infection.
Actinomycosis
The causative agent, the anaerobic branching gram-positive filamentous organism
Actinomyces israelii, is present on the surface of normal and within carious teeth. The
pathogenesis of this infection is believed to be the entry of this normal oral saprophyte
through the extraction site of a host with poor dental hygiene. The infection initially
produces a lytic lesion in the bone (generally the mandible) and then extends into the soft
tissues. The full clinical picture of cervicofacial actinomycosis is one of a painful
indurated swelling with areas of suppuration that have fistulous tracts through the skin.
From these tracts, colonies of twisted myocele filaments, termed sulfur granules, may be
found in the exudate. The final diagnosis depends on isolation of the organism in culture.
Radiography reveals a nonspecific pattern of bone erosion.
The key to controlling actinomycotic infections is to prevent relapses by prolonged
antimicrobial therapy. Penicillin is administered for 1 year. Tetracycline is substituted in
penicillin-allergic patients (7).
Septicemia
The bacteremia resulting from oral cavity instrumentation
(both periodontal and surgical) and its potential for
producing sub-acute bacterial endocarditis are well
recognized. The offending organism predominantly
encountered is the normal oral saprophyte Streptococcus
viridans; however, endocarditis of dental origin also has
been reported with gram-negative bacteria. We have seen
septicemia produced by the anaerobe Fusobacterium,
resulting in multiple metastatic abscesses (liver, femur)
in a healthy child with a pulpally injured tooth. In
another patient, an immunocompetent young woman, a
bacteremia with Streptococcus pneumoniae developed
following gingival curettage, which produced an adult
respiratory distress syndrome and disseminated
intravascular coagulation with a fatal outcome (Table 48.3
and Table 48.4).

TABLE 48.3. COMPLICATIONS
ODONTOGENIC INFECTIONS



TABLE 48.4. EMERGENCIES ODONTOGENIC
INFECTIONS



Before any operative procedures are performed in the oral cavity, the patient should be
questioned regarding a history of congenital or rheumatic heart disease and the placement
of an artificial heart valve. Presently, mitral valve prolapse is one of the most common
indications for antibiotic prophylaxis for dental surgery. Prophylaxis consists of the oral
administration of 3 g of ampicillin.
Disseminated sepsis secondary to infections of the oral cavity is not a curiosity. Navazesh
et al. (8) reported a case of toxic shock syndrome with multisystem failure requiring life
support in a man following extraction of a carious mandibular molar tooth.

HIGHLIGHTS
Carious and periodontally involved teeth may be
the source of life-threatening infections.
The extent and severity of the infection do not
correlate with the clinical state of the tooth
or the dental radiographic findings.
Although penicillin covers most infections
produced by the oral flora, it is inadequate
for deep-space infections where gram-negative
rods and -lactamaseproducing and anaerobic
organisms may be involved.
Serious dental infections (deep-space
infections, necrotizing and gas-forming
infections, septicemia) can arise in
immunocompetent hosts.
With Ludwig angina, the immediate therapeutic
goal is to secure the airway by tracheostomy.
Deep fascial space infections require surgical
drainage in addition to antibiotic therapy to
prevent serious complications (e.g., carotid
rupture, mediastinitis).
Antibiotic prophylaxis is essential to prevent
subacute bacterial endocarditis following even
minor dental operative procedure in patients
with cardiac valvular disease or prosthetic
heart valves.
CHAPTER REFERENCES
1. Marple BF. Ludwig angina. Arch Otolaryngol Head Neck Surg
1999;125:596598.
2. Quinn FB Jr. Ludwig angina. Arch Otolaryngol Head Neck Surg
1999;125:599.
3. Shockley WW. Ludwig angina. Arch Otolaryngol Head Neck Surg
1999;125:600.
4. Bradon JD, Lutwick LI. Retropharyngeal space infections in a
community hospital. Am J Emerg Med 1991;9:77.
5. Krespi YP, Lawson W, Blaugrund SM, et al. Massive necrotizing
infections of the neck. Head Neck Surg 1981;3:475.
6. Langford FP, Moon RE, Stolp BW, et al. Treatment of cervical
necrotizing fasciitis with hyperbaric oxygen therapy. Otolaryngol
Head Neck Surg 1995;112:274278.
7. Belmont MJ, Behar PM, Wax MK. Atypical presentations of
actinomycosis. Head Neck Surg 1999;21:264268.
8. Navazesh M, Mulligan R, Sobel S. Toxic shock and Down syndromes
in a dental patient. Spec Care Dentist 1994;14:246251.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

49 TEMPOROMANDIBULAR JOINT DISORDERS
Head & Neck SurgeryOtolaryngology
49




TEMPOROMANDIBULAR JOINT DISORDERS
WILLIAM C. DONLON

W.C. Donlon: Department of Surgery, Mills-Peninsula Hospitals,
Burlingame and San Mateo, California; Department of Surgery, Sequoia
Hospital, Redwood City, California.


Controversies about various sources of chronic pain have smoldered for decades, and the
temporomandibular joint (TMJ) must rank near the top of the list of these disputes.
Unsubstantiated theories and unscrupulous clinicians have confounded the debate.
Fortunately, the last 20 years have brought great advances in diagnosis and therapy, and
although a consensus will not be reached soon, medical and dental experts now agree on
some core concepts about the cause and treatment of TMJ and related disorders.
Medical, dental, and surgical concepts are now melding into a new synthesis, and the
time for nonspecific diagnosessuch as Costen syndrome, TMJ syndrome, or myofascial
pain dysfunction syndromehas passed. The astute clinician must be able to differentiate
true articular diseases from muscular disorders, and generic treatments or referrals are no
longer appropriate.
The TMJ is susceptible to all the afflictions of other joints. Conversely, there are no
articular conditions unique to the jaw joint. The same rules apply to the masticatory
muscles. This chapter covers a range of organic and functional afflictions of the
stomatognathic system.
The central presenting symptom of most conditions in the constellation of TMJ disorders
is acute or chronic pain. The International Association for the Study of Pain defines pain
as an unpleasant sensory and emotional experience associated with actual or potential
tissue damage or described in terms of such damage. Pain is always subjective. It is
unquestionably a sensation in a body part, but it is always unpleasant and therefore an
emotional experience.
It is important for the clinician to acknowledge that all pain has both physical and
emotional components and that these are inextricable. All pain is real, and the patient's
description and quantization must be accepted as accurate. Pain is always described in
terms of organic lesions, whether or not such lesions exist.
ANATOMY
Applied Neuroanatomy
Muscular Disorders
Most patients with myogenic pain have normal TMJs (Fig. 49.1). By reason of history
and anatomic coincidence, they have been included in this chapter.

FIGURE 49.1. Components of the temporomandibular
joint. AE, articular eminence and disk attachment; APF,
attachment to the pterotympanic fissure; CPW, capsule,
posterior wall; D, disk; F, fascia; ILT, inferior head of the
lateral pterygoid muscle; LPP, lateral pterygoid plate;
PCA, posterior condylar attachment; SLT, superior head
of the lateral pterygoid muscle.



Abnormalities of the masticatory muscles can be divided into organic and functional
conditions. Because organic diseases such as hemifacial hypertrophy or atrophy rarely
cause pain or require comprehensive craniomaxillofacial evaluation and treatment, they
are not considered here. True spasms, involuntary convulsive muscular contractions, of
the masticatory muscles are also rare. When they occur, central neurologic pathology
must be ruled out.
Most painful disorders of the chewing muscles are functional in nature and lack discrete
organic pathology. Studies aimed at revealing physiologic abnormalities of affected
muscles [i.e., invasive electromyography (EMG)] have revealed some alterations, but
these have proved neither consistent nor diagnostic. Pain of the masticatory muscles must
be considered to be the result of hyperactivity or hyperfunction. As such, these conditions
should be classified as strains, injury by overuse or improper use.
Many patients presenting for treatment of muscle pain give a history of nocturnal or
diurnal bruxism (i.e., jaw clenching). Some patients may have clinical evidence of such
behavior (i.e., attrition of the dental occlusion) but are unaware of its occurrence. A third
group may have myogenic pain without a history or signs of masticatory strain. Surface
EMG of symptomatic patients yields a wide range of results and cannot be used as a
diagnostic tool. EMG is thought to be useful as a baseline for biofeedback training.
Until recently, myofascial pain dysfunction and related terms were used to classify
masticatory muscle pain conditions. These terms are 30 years old and are based on
outdated assumptions, and there are multiple definitions for myofascial pain dysfunction
syndrome. The astute clinician should abandon this terminology.
During the 1980s, the term fibromyalgia came to the forefront in rheumatology and
orthopedics. A condition found predominantly in women, fibromyalgia is defined as a
chronic, diffuse, musculoskeletal pain and a sleep disorder, without evidence of arthritis
or myositis. The literature initially focused on the extremities and trunk, but the head and
neck are now included in the condition. Many patients presenting for treatment of
masticatory muscle pain report other areas of rheumatic pain in anamnestic
questionnaires, and they commonly have disturbed sleep, including bruxism. Currently,
we diagnose myogenic pain as masticatory or head and neck fibromyalgia (1). This is
often one component of generalized fibromyalgia involving the back, abdomen, or
extremities. We apply the same treatment concepts to the head and neck as those
advocated for fibromyalgia of the lower quadrants.
For decades, the dental occlusion has been a central theme in the debates about TMJ
disorders. These disorders were often attributed to malocclusions, and treatment focused
on altering the occlusal form and function. The assumption that the teeth must be
responsible for some head pains was probably a natural one because of the unique
anatomy. The maxilla and mandible are the only bones with their own adnexa, the teeth.
The TMJ is the only synovial joint with a fixed end point of closure (i.e., when the teeth
occlude). The fact that no one has an ideal occlusion added fuel to the fire because some
malocclusion could be identified in every patient with head and neck pain. The
simultaneous occurrence of pain and malocclusion was assumed to be a cause-and-effect
relationship, but this did not explain the majority of malocclusions that were not
associated with any pain disorder.
Occlusal considerations are a peripheral issue in most musculoskeletal pain disorders.
The teeth are innocent victims rather than wanton malefactors. Treatment of the
occlusion is usually geared toward protecting the dentition and periodontium from the
effects of misuse, such as bruxism.
Temporomandibular Joint Disorders
Internal derangements include all the abnormal processes that occur within the confines
of a joint capsule. The internal derangements of the TMJ are the same as for any other
joint: disk displacements, osteoarthrosis (e.g., degenerative joint disease), inflammatory
arthritides (e.g., rheumatoid diseases), congenital deformities (e.g., condylar aplasia),
developmental deformities (e.g., condylar hyperplasia), ankylosis, fractures, and
neoplasms.
Common usage equates the term internal derangement with disk displacement. This
chapter follows this convention rather than the stricter orthopedic usage.
Disk displacements are caused by disruption of the ligamentous attachment of the disk to
the condyle and the subsequent pull of the lateral pterygoid muscle. The mechanism of
ligament stretch or tear may be as obvious as acute blunt trauma to the mandible or may
be as subtle as systemic joint hypermobility. Causes of ligament disruption include purely
structural weakness, blunt facial trauma, and mandibular hyperextension. Hyperextension
may be caused by prolonged dental appointments, forceful third molar removal, difficult
intubation, and subluxation during tonsillectomy.
Autoradiographic studies have demonstrated estrogen receptors in the ligaments of the
primate TMJ and confirmed sexual dimorphism in the concentration of these sex
hormone receptors. This dovetails nicely with the high female-to-male ratio of TMJ disk
derangements. Clinical studies have confirmed an increased frequency of generalized
joint hypermobility in the population of patients with TMJ internal derangements (2).
Hypermobilities are more common in women than in men.
By far, the most common vector of displacement of the temporomandibular disk is in the
anteromedial direction because of the orientation of the lateral pterygoid muscle. The
degree of displacement correlates with clinical symptoms. Several investigators have
proposed classifications for these anterior disk displacements. The one developed at our
institution divides disk displacements into three types. The type Ia internal derangement
presents with a nonpainful click during the opening or closing movements of the
mandible. The noise occurs as the condyle moves under the anteriorly displaced disk
during opening and again as the disk is held anteriorly while the condyle moves
posteriorly during closure. A type Ib derangement is the same as type Ia but has pain as
part of the condition.
The exact cause of the pain component is thought to be part mechanical and part
chemical. With the disk displaced anteriorly, the meniscotemporomandibular frenum
(i.e., retrodiskal pad) is stretched over the condyle and compressed between the bony
components. The chronic irritation causes inflammation of the synovium and release of
noxious peptides (e.g., substance P) into the synovial fluid.
The patient with a type II displacement has the same clinical presentation as the type Ib
patient. The maximal oral opening is the normal interincisal distance of 40 to 50 mm, and
there are clicking sounds during opening or closing. Unlike the type I patient, the type II
patient gives a history of locking (i.e., inability to open the mouth fully). The closed lock
is caused by the inability of the condyle to translate under the disk. The disk therefore
becomes a mechanical obstacle to normal condylar movements. This may occur
intermittently due to changes in disk position, distortion of the normal disk morphology,
or changes in the normal synovial lubrication of the joint.
A type III internal derangement is a persistent closed lock. In this patient, there is no
translation of the condyle under the displaced disk. Hence, there are no joint clicks, and
the maximal opening is reduced.
These types represent the clinical progression of the stages in chronic disk derangement.
A patient with a type II derangement often gives a history of having passed through the
phases of type Ia and Ib, and many type III patients present with a history that
recapitulates the type I and type II signs and symptoms.
Outcome predictors correlate well with the stage of derangement. The best prognosis is
for a nonpainful click that occurs early in the opening motion. (The earlier the click, the
less displaced is the disk.) A painful, late click is less likely to respond to primary
intervention, and a type III derangement almost always requires surgical treatment for
clinical improvement to take place within a reasonable period. Because duration of
symptoms is highly weighted in the prognosis equation, early treatment or referral is
imperative for disk derangements. A surgeon should be included in the early phase of
treatment planning to ensure proper sequencing of nonsurgical and surgical modalities.
Degenerative joint disease is the loss of articular tissues. This usually means destruction
of the articular fibrocartilage of the condyle and fossa, in part or whole, and metaplastic
or destructive changes in the disk and its attachments. This has usually been thought of as
a noninflammatory, mechanical process (i.e., wear and tear) and is most properly referred
to by the synonymous term osteoarthrosis. The American literature has favored the term
osteoarthritis. Inflammation in the TMJ is primarily seen in the form of synovitis. This
condition is thought to be the result of particulate debris buildup following
microfibrillation with resultant microtrauma and the production of inflammation
mediators via the arachidonic acid cascade.
Temporomandibular joint surgeons often describe findings consistent with inflammation
(e.g., synovial hyperplasia, hypervascularity, or chondromalacia) during direct
examination of traumatized TMJs without systemic inflammatory disease. Arthritis may
be part of the continuum of degenerative joint disease for the TMJ and is actually
secondary to the osteoarthrotic process.
The patient with temporomandibular degenerative joint disease may present with
preauricular pain, otalgia, lateral and endaural palpation tenderness, or crepitant joint
sounds on auscultation. Radiographs can confirm the diagnosis (3).
Degenerative joint changes probably represent the end of a series of soft tissue internal
derangements. For years, the debate raged over whether the bone spur caused the
retrodiskal perforation or the spur grew in response to the perforation. Experimental and
clinical evidence points to the disk and ligament changes preceding the bony
deterioration. Radiographic evidence of bony degeneration of remodeling therefore
indicates long-standing disk and capsular disorders. Nonetheless, clinical internal
derangement disease is usually a condition of young adult women. If degenerative joint
disease is the end stage of disk disease, why are there not more elderly patients with
related complaints? The most logical explanations are that the pain component of this
condition is self-limiting (i.e., nociceptive nerve vascularity and viability decrease with
chronicity) and that elderly patients exert less masticatory load due to compromised
dental status. These speculative explanations are consistent with histopathologic and
biophysical findings.
Congenital and developmental internal derangements in-clude branchial arch syndromes,
hemifacial microsomia, isolated condylar aplasia or hypoplasia, and condylar
hyperplasia. These usually manifest as facial asymmetries and dental malocclusions.
Correction requires repair of the joint and reconstruction of the teeth, jaws, and face by
means of orthodontics, orthognathic surgery, and soft-tissue augmentation. In the
growing patient, growth center transplantation by costochondral grafting is the accepted
approach, although growth is unpredictable. In the adult, autogenous or alloplastic
reconstructive approaches have been advocated. Each case must be evaluated
individually.
Ankylosis is divided into fibrous and bony types. Fibrous ankylosis may be the result of
chronic inflammation or disuse. Various degrees of fibrosis are seen with disk
displacements. Bony ankylosis may reflect partial ossification of the joint complex or
complete fusion of the mandible to the temporal bone.
The partial form is the end stage of chronic capsulitis and presents at surgery as a bony
bridge between the lateral fossazygomatic process and the lateral condyloid process.
After this bone bridge is removed, a normal or near-normal joint may be encountered
more medially (Fig. 49.2).

FIGURE 49.2. Artist's representation of partial or
juvenile ankylosis.



Complete ankylosis or fusion may result from untreated or ill-treated condylar trauma or
from chronic arthritis without proper physiotherapy. Before the antibiotic era, ankylosis
or other forms of condylar dysplasia were well-known sequelae of mastoiditis and
chronic otitis media. Today this complication is rare in Western societies other than
emerging countries.
IMAGING
The first radiographic images of the TMJ were published in the 1930s. Tomography was
applied in the 1940s, and little changed until the 1970s. Nrgard described TMJ
arthrography in the 1940s, but his work was overlooked for 30 years. In the late 1970s,
arthrographic techniques were used for arthrography in several centers. This quickly
became the gold standard for evaluating disk displacements. Videofluoroscopy was used
for dynamic imaging, and arthrotomography provided a static hard copy. The early 1980s
saw the application of computed tomographic (CT) technology to the diagnosis of
internal derangement and maxillofacial bone deformities. The first reports in the United
States of the use of magnetic resonance imaging (MRI) in TMJ imaging were in 1984 and
1985. These modalities have been compared in the literature.
Magnetic resonance imaging is noninvasive and does not use ionizing radiation. It is the
best technique for evaluating disk morphology and position and is the most sensitive
indicator of early degenerative bone changes (Fig. 49.3). It lacks dynamic viewing for
most applications, fine resolution to disclose perforations, three-dimensional formatting,
and CAD-CAM capabilities. The cost has limited its availability, but this is improving
dramatically in many areas. Our recommendations for diagnostic imaging are listed in
Table 49.1.

FIGURE 49.3. Sagittal magnetic resonance imaging of
the temporomandibular joint shows anterior disk
displacement with normal disk morphology.



TABLE 49.1. DIAGNOSIS AND
RECOMMENDATIONS FOR IMAGING



TREATMENT
Table 49.2 summarizes the medical and surgical treatment available for muscle, disk, and
joint disorders.

TABLE 49.2. TREATMENT
TEMPOROMANDIBULAR JOINT DISORDERS



Muscular Disorders
The treatment of fibromyalgia (Table 49.3) includes a broad range of
pharmacotherapeutic agents and ancillary therapies. Drug regimens include nonsteroidal
antiinflammatory medications drugs (NSAIDs), muscle relaxants, antispasmodics,
narcotic compounds, hypnotics, tranquilizers, and antidepressants. In treating head and
neck manifestations of muscle pain, all of these compounds are used (only rarely the
benzodiazepines or tricyclic compounds).

TABLE 49.3. TREATMENT MUSCULAR AND
JOINT DISORDERS



Almost all patients receive initial treatment with NSAIDs and muscle relaxants (Table
49.4).

TABLE 49.4. MEDICATIONS FOR MUSCULAR
DISORDERS



Medications with the longest half-lives are preferred to maximize patient compliance.
However, minimizing adverse side effects (e.g., gastritis) often dictates the prescribed
medication. The use of histamine (H
2
)-antihistamines or prostaglandin inhibitors (e.g.,
misoprostol) can minimize side effects and permit the use of the NSAIDs where
previously not possible.
With muscle relaxants and antispasmodics, the starting medication should be chosen with
an eye toward maximizing patient acceptance and compliance. Patients are often allowed
to increase the daily dose at their own pace until the recommended dosage is reached.
Some of the antispasmodics, such as baclofen and clonazepam, have been shown to have
central analgesic properties. Most of the commonly known muscle relaxants do not relax
skeletal muscle but are thought to act as minor tranquilizers.
Orthotic therapy is often recommended for this patient population after initial drug
therapy. The basic concept in splint design for muscle disorders is to prevent tight
intercuspation of the teeth and excessive muscle contraction. Our dentists use full-
coverage flat-plane splints for this purpose (Fig. 49.4). The orthotic is worn full time for
several weeks. NSAIDs and muscle relaxants are continued during this period.

FIGURE 49.4. Muscle-neutralizing (flat plane) orthotic
appliance.



Behavioral therapy, including biofeedback methods, relaxation techniques, muscle
retraining, and exercise, is frequently recommended to complement the splint and
medication. Physical therapy may play a supportive role in the care of some fibromyalgia
patients.
It is important for splint wear to be monitored by the dentist. Ideally, the total hours of
use is reduced gradually after the initial treatment period. If patients are nocturnal
bruxists who awake with symptoms of muscle sprain, nighttime use only is continued for
several more weeks. If daytime clenching or grinding is the problem, splints are inserted
only during painful periods.
Long-term splint wear is avoided, except to protect the dentition in cases of severe
bruxism. No cure is known for bruxism, and irreversible dental treatments are
contraindicated. Some appliances, such as soft splints or mouth guards, can induce excess
jaw movement and are to be avoided in this patient population.
Muscle relaxants, antispasmodics, and hypnotics may have to be discontinued gradually
if they have been used on a chronic basis. Medication holidays may be helpful in
avoiding withdrawal phenomena and in determining the need to continue active therapy.
These nonorganic muscle disorders are thought to be self-limiting, and patients need to be
reassured that they will ultimately feel well without the need for prolonged use of
medications or splints.
Joint Disorders
Early diagnosis and treatment of joint disease are the key to success (Table 49.3). If
referral is contemplated, a TMJ surgeon will know whether to recommend nonsurgical
therapy or to proceed with early surgical repair. Prolonged dental or occlusal therapy for
internal derangements of the joint are contraindicated, and these treatments inevitably
decrease surgical success rates.
Nonpainful clicking joints do not require treatment unless the joint noise is socially
unacceptable. Longitudinal studies suggest that most clicks do not progress to painful
disorders or limited range of motion, nor can current diagnostic techniques disclose
which patients with nonpainful clicking jaw joints will become symptomatic.
The painful clicking joint requires intervention. Painful early clicks (i.e., 2 to 3 mm after
disocclusion of the teeth) can often be managed with nonsteroidal analgesics and soft diet
and can resolve with definitive intervention.
Patients with painful late clicks (i.e., occurring closer to the end of jaw movement) or
painful clicks with locking are less likely to respond to nonsurgical therapy. In addition to
repositioning splints, jaw mobilization by conventional active and passive physical
therapy or under anesthesia can provide temporary disk reduction. Acute mobilization
procedures often require intravenous sedation or general anesthesia for the best patient
relaxation and maximal benefit. If these patients do not respond to mobilization, surgical
joint reconstruction is required.
Manual mobilization under anesthesia combined with ar-throcentesis (i.e., hydraulic
pumping) may improve the range of motion for a type II displacement, permitting
conventional physical therapy and home care to proceed. Most of the literature on this
procedure is limited to the treatment of acute closed locks, that is, nonreducing disk
dislocations or type III displacement. In this patient group, success rates exceed 90% in
anamnestic retrospective studies (4).
Arthroscopic lavage and lysis of adhesions are required in some cases and yield the best
results in acute nonreducing disk displacements. Restoration of diskcondyle
relationships is not the goal of either arthrocentesis or arthroscopy. These procedures are
thought to restore the mobility of the joint by reestablishing joint lubrication and fluidity.
Release of a partial vacuum between the displaced disk and the fossa also has been
postulated as a reason for their success. Physical therapy and jaw exercises should follow
all closed mobilizations, arthrocenteses, and arthroscopies.
Surgical Techniques
Temporomandibular joint surgery can be divided into closed (i.e., arthroscopy) and open
(i.e., arthrotomy) categories (5). Anesthesia for either technique is usually by means of
nasoendotracheal intubation to allow duplication of all mandibular positions during
anesthesia without interference from the airway. Arthroscopy can be performed
successfully with auriculotemporal nerve block and sedation.
During arthroscopy, a cannula of approximately 2 mm in diameter is passed into the
upper joint compartment by a lateral percutaneous or endaural approach. A miniaturized
video camera is attached to the lens, as is a fiberoptic light cable. The image is viewed on
a video monitor and can be videotaped or photographed (Fig. 49.5).

FIGURE 49.5. Arthroscopic view of the
temporomandibular joint shows the glenoid fossa,
perforation of the retrodiskal area, and posterior condylar
articular surface.



Arthroscopy has a role as a diagnostic tool and may replace or supplement radiographic
images. Secondary ports can be established from a lateral percutaneous approach to allow
introduction of hand instruments for synovial biopsy, disk remodeling, and lysis of
adhesions. Miniaturized rotary instruments are available for removing irregular cartilage
or bone, fibrous adhesions, or synovial enlargements (e.g., pannus formation). The
wounds created by inflow and outflow portals may require a single fine suture for closure
or may be covered with a liquid wound dressing, such as benzoin or collodion, without
suturing. Adhesive bandages are applied as the only dressing.
There are many approaches to open joint surgery (Fig. 49.6). The most commonly used
skin incision is the preauricular type. We prefer endaural or postauricular incisions for
reasons of cosmesis and protection of the upper branches of the facial nerve. The
endaural incision follows the curvature of the anterior helix from the hair line, continues
behind and transects the tragus, and ends at the insertion of the lobule. The incision is
deepened to the level of the temporalis fascia and lateral ligament. The postauricular
incision reaches this plane by making a curvilinear incision along the length of the
insertion of the ear skin through the postauricular muscle to the mastoid fascia.
Dissection proceeds anteriorly to isolate the external auditory canal. A no. 10 Bard-
Parker blade is used to transect the canal as superficially as possible. The pinna is
retracted anteriorly. Both the endaural and postauricular incisions can be extended
anterosuperiorly into the temple if additional exposure is needed.

FIGURE 49.6. Surgical approaches to the
temporomandibular joint. A, preauricular; B, endaural; C,
postauricular or transmeatal; A8, temporal extension; B8,
temporal extension; B, perimeatal extension; C8,
temporal extension.



An inverted hockey stick incision is made through the superficial temporalis fascia and
posterior lateral ligament. The deepest part of this incision is the zygomatic periosteum.
The Freer is used to reflect all tissues anteriorly until the articular eminence is exposed. A
Weitlander-type self-retaining retractor can then be used. At this point, the intact lateral
capsule is in the surgeon's view. It is incised in a manner paralleling the lateral glenoid
fossa, allowing access to the superior joint space. A second horizontal incision is made
along the posterolateral condylar neck. The periosteum is elevated superiorly to enter the
lower joint space and condylar articulating surface.
The surgical options at this point depend on the intracapsular findings. If the disk is
sound, it can be repositioned over the condyle with plication of the retrodiskal tissue and
reattachments of the ligaments.
If the disk is not salvageable, it can be excised. If articular cartilage is damaged,
reconstruction by autogenous auricular cartilage graft (Fig. 49.7) is desirable (6). The
conchal cartilage is an excellent donor source. The cavum conchae recapitulates the
three-dimensional topography and dimensions of the glenoid fossa. It can be harvested
from anterior or posterior approaches. The author distinctly prefers the posterior approach
when harvesting conchal cartilage for glenoid fossa augmentation (Fig. 49.8). When
appropriate, a modified single incision for postauricular approach to the TMJ will allow
harvesting the graft without a separate donor site. The perichondrium is left attached to
the concave (posterior) surface, whereas the dissection of the anterior (convex) surface is
subperichondrial. The perichondrium is placed against the fossa to allow for biologic
fixation. Immediate fixation is accomplished by drilling three bone holes and suturing the
disk to the lateral fossa with 4-0 stainless-steel tendon sutures. The condyle then
functions against the neofossa.

FIGURE 49.7. Conchal cartilage can be fixed to the
glenoid fossa as an autogenous replacement of the disk or
articular cartilage. (Courtesy of Dr. Ralph Merrill.)



FIGURE 49.8. Harvesting conchal cartilage.



Another means of interposing tissue between the bony surfaces is by rotation of a
pedicled temporalis fascia or pericranial temporalis flap (Fig. 49.9). Closure is obtained
in a standard layered fashion, and mastoid-type pressure dressings are applied.

FIGURE 49.9. Axial temporalis flap rotated into the
temporomandibular joint as an interpositional graft.



For reconstruction of the condyle, a submandibular incision is added for access to the
lower vertical ramus. Costochondral grafts can be inserted with or without auricular
cartilage or temporalis flap interposition. Typically, the fifth, sixth, or seventh rib is
harvested via an inframammary approach. After the rectus abdominis and pectoralis
major muscles are identified, dissection continues between them to expose the lateral
periosteum of the rib or ribs. The periosteum is incised and reflected superiorly and
inferiorly. In children, the lateral perichondrium is left intact to prevent avulsion of the
cartilage component. This maneuver is not necessary in adults. A Doyen elevator is
designed to elevate the medial periosteum. After this is completed to the desired length
(typically 60 to 80 mm), the medial surface of the sternal insertion is protected with a
malleable retractor, and a 1-cm cap of cartilage is created with a full-thickness incision
using a no. 10 scalpel blade. The rib is then elevated, a rib cutter is inserted, and the graft
is separated. The surgical site should be filled with saline and the lungs hyperinflated by
the anesthesiologist to check for pleural tears. If no bubbles appear, the periosteum is
reapproximated, and the wound is closed. If there are small tears with normal lung
insufflation, they can be repaired. A large tear or frank pneumothorax requires standard
chest tube insertion. A postoperative chest radiograph should be obtained in the recovery
room.
During condylar replacement surgery, it is necessary to establish maxillomandibular
fixation to maintain the proper dental occlusion postoperatively. Many protocols
recommend coronoidectomy for prosthetic joint replacement. This is accomplished from
a posterior mandibular vestibule incision and stripping the temporalis insertion from the
anterior vertical ramus and coronoid. The coronoid process is incised with a drill or saw
and delivered into the oral cavity. The best method for fixation of the graft to the
recipient site is by placement of a miniplate with monocortical screws. Screw holes are
left open to allow for lag screw fixation to the vertical ramus. In addition, several screw
holes should extend past the rib's edge. This lollipop effect allows for easy handling and
manual stabilization of the graft. After fixation, the protruding portion of the plate is
removed with a drill or plate cutter (7) (Fig. 49.10; see also Color Plate 15 following p.
370).

FIGURE 49.10. Miniplate secured extracorporally to
distal aspect of rib in lollipop fashion with two bicortical
screws. After ensuring proper positioning, the graft is
secured with two or more additional screws placed
bicortically through the ramus. The excess plate length is
then trimmed. (See also Color Plate 15 following p. 370.)



For extended resection of the TMJ and lateral access to the infratemporal fossa and skull
base, the condylectomy procedure is modified by storing the condylar neck in culture
medium or physiologic electrolyte solution. The zygomatic arch is then osteotomized and
retracted laterally while pedicled to the origin of the masseter muscle. The coronoid
process is osteotomized, and the temporalis muscle is then retracted superiorly to allow
complete access to all joint components, masticatory muscles, and retromaxillary and
skull base structures (Fig. 49.11). Postresection, the condyle is replaced as described for
costochondral grafts, and the zygoma is returned to its normal position. If the arch is not
stable, a miniplate is used to complete fixation (Fig. 49.12; see also Color Plate 16
following p. 370).

FIGURE 49.11. AD: Lateral approach to associated
joint structures, infratemporal and retromaxillary spaces,
and the lateral skull base.



FIGURE 49.12. After resection, the osteotomized
condyle is repositioned and fixated with a miniplate. The
osteotomized zygoma has been reduced and fixated with
a microplate. (See also Color Plate 16 following p. 370.)



Temporomandibular joint surgery can be performed simultaneously with orthognathic
procedures necessary to restore or improve maxillomandibular relationships (Fig. 49.13).
After condyle replacement surgery, maxillomandibular fixation is usually maintained for
several days. After releasing the fixation, intermaxillary guiding elastics should be used
for several weeks. Soft diets are usually enforced during this period.

FIGURE 49.13. Postoperative cephalogram of
simultaneous temporomandibular meniscorrhaphy and Le
Fort I osteotomy. The maxillary surgery was performed
because an anterior open bite developed after prolonged
splint therapy.



Aggressive postoperative physical therapy and home exercises begin as soon as possible.
Stretching exercises are often begun the day of surgery for procedures without
maxillomandibular fixation. Active and passive mobilization, ultrasonography,
phonophoresis, and other physical therapy modalities are usually begun in 1 to 2 weeks.
Some passive motion machines are available for the jaw, and these may augment
traditional therapy and home exercise. Patients are instructed to keep food consistency to
a comfortable level and to advance to a regular diet as quickly as tolerated. Other
surgeons believe soft or nonchewing diets are advisable for weeks or months after
surgery. No studies have demonstrated the benefit of one approach over another.
A recent analysis of four randomized, controlled trials of acupuncture versus sham
acupuncture, standard therapy, or no treatment favored acupuncture as a symptomatic
treatment for TMJ disease (8). However, these results should be interpreted cautiously
because none of the trials were performed with blinded evaluators.
Patients undergoing any TMJ surgery should be advised of the potential for persistent
crepitus, occasional pain, and masticatory disorders. The preoperative consultation should
include the risks of facial paresis, dysesthesias, occlusal changes, scars, auditory canal
stenosis, implant failure, and the associated risks of any autogenous grafts (e.g.,
pneumothorax).
CONCLUSION
The ability to diagnose and treat diseases and disorders of the TMJ and stomatognathic
complex has never been more thorough or accurate. Predictable treatment regimens are
available, and appropriate therapies can be instituted without delay. Surgery is no longer
considered a treatment of last resort. In some cases, surgery should be considered the
primary, conservative intervention.
The importance of working with a well-trained team or referral group cannot be
overemphasized. Generic referral to the patient's dentist is no longer appropriate after ear
disease has been ruled out as a cause of preauricular or panfacial pain. All the
components of multimodal treatment are necessary for the most reliable outcome and the
quickest success.

HIGHLIGHTS
Temporomandibular joint syndrome is an outdated
concept.
Most TMJ pain is muscular rather than joint
pain.
Early intervention for disk displacements is
the key to success.
Imaging is indicated for confirmation of disk
pathology and bone status before surgery or to
establish a treatment baseline.
Early surgery is conservative therapy for
painful disk disease.
Disk repair surgery is the mainstay for disk
displacement.
Arthrocentesis and arthroscopy are effective
for early nonreducing disk displacement.
Conchal cartilage is an excellent donor source
for replacement of articular cartilage and
interpositional tissue mass.
Ankylosis and secondary arthritic deformities
can be successfully treated with autogenous
reconstruction.
Reconstructive procedures can be combined to
satisfactorily restore form and function in
lieu of a U.S. Food and Drug Administration
(FDA)-approved joint prosthesis.
Orthognathic surgery may be necessary to
restore the occlusion after prolonged disease
or occlusal-oriented therapy.
CHAPTER REFERENCES
1. Truta MP, Santucci ET, Donlon WC, et al. Head and neck
fibromyalgia and temporomandibular arthralgia. In: Jacobson AL,
Donlon WC, eds. Headache and facial pain. New York: Raven,
1990:141.
2. Westling L, Carlsson GE, Helkimo M. Background factors in cranio-
mandibular disorders with special reference to general joint
hypermobility, parafunction, and trauma. Craniomandib Disorders
Facial Oral Pain 1990;4:89.
3. Bush FM, Harkins SW, Harrington WG. Otalgia and aversive symptoms
in temporomandibular disorders. Ann Otol Rhinol Laryngol
1999;108:884892.
4. Kendall BD, Frost DE. Arthrocentesis. Atlas Oral Maxillofac Surg
Clin North Am 1996;4:1.
5. Frost DE. Joint preservation procedures. Atlas Oral Maxillofac
Surg Clin North Am 1996;4:1.
6. Waite PD, Matukas, VJ. Use of auricular cartilage as a disc
replacement. Oral Maxillofac Surg Clin North Am 1994;2:349.
7. Donlon WC. Associated bony procedures for preservation. Atlas
Oral Maxillofac Surg Clin North Am 1996;4:107.
8. Ernst E, White AR. Acupuncture as a treatment for
temporomandibular joint dysfunction. Arch Otolarygnol Head Neck
Surg 1999;125:269272.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

50 SNORING AND OBSTRUCTIVE SLEEP APNEA
Head & Neck SurgeryOtolaryngology
50




SNORING AND OBSTRUCTIVE SLEEP APNEA
REGINA PALOYAN WALKER

R.P. Walker: Department of Otolaryngology, Loyola University, Maywood, Illinois.


Epidemiology
Snoring
Obstructive Sleep Apnea
Sleep Physiology
Normal Sleep
Sleep-Disordered Breathing
Sleep Disorders
Snoring
Upper Airway Resistance Syndrome
Obstructive Sleep Hypopnea Syndrome
Obstructive Sleep Apnea Syndrome
Physiology of Upper Airway Obstruction
Clinical Evaluation of the Suspected Sleep Apnea Patient
History
Physical Examination
Radiographic Evaluation
Cephalometric Roentgenograms
Computed Tomography and Magnetic Resonance Imaging
Diagnostic Studies
Oximetry
Acoustic Recording Devices
Portable Polysomnography
Polysomnography
Multiple Sleep Latency Test
Preoperative Medical Evaluation of Patients with Obstructive Sleep Apnea Syndrome
Cardiopulmonary Disease
Hypothyroidism and Acromegaly
Obesity
Other Disorders Associated with Obstructive Sleep Apnea Syndrome
Approach to Treating Snoring and Obstructive Sleep Apnea Syndrome
Indications for Treatment
Behavioral Treatment for Snoring and Obstructive Sleep Apnea Syndrome
Nonsurgical Treatment of Snoring and Obstructive Sleep Apnea Syndrome
Surgical Treatment for Snoring
Surgical Treatment of Obstructive Sleep Apnea Syndrome
Anesthetic Management of Patients with Obstructive Sleep Apnea Syndrome
Nasal Surgery
Palatal Surgery
Tongue-Base Reduction Procedures
Maxillomandibular Procedures
Mandibular Osteotomy with Genioglossus Advancement
Hyoid Myotomy and Suspension
Maxillomandibular Osteotomy and Advancement
Tracheotomy
Chapter References
EPIDEMIOLOGY
Snoring
Snoring is a common problem that has plagued bed partners for centuries. In the 1970s,
research demonstrated that 40% of men and 28% of women snored and that the
prevalence of snoring increases with age. More recent data from the Wisconsin Sleep
Cohort Study found that in men and women 30 to 60 years of age, 28% of women and
44% of men reported habitual snoring. Researchers studied snoring in more than 2,000
Canadians and found that 42% of all these people reported snoring. This report also noted
that the prevalence of snoring increased up to the seventh decade of life, with 84% of
men and 73% of women reporting snoring in this age group.
Unfortunately most epidemiologic data on snoring comes from self-report questionnaires.
The information obtained from these questionnaires is often inaccurate because the
patient is usually the least aware of his or her own snoring habits. Even if the snoring
information is from a bed partner, the information remains subjective. A bed partner who
is a light sleeper may be disrupted by the occasional snore, whereas other bed partners
adjust to the snoring and are disrupted only by very loud crescendo snoring.
Although objective testing is essential, at this time there is no standardization of what
spectral characteristics make up the snoring sound. Studies have been performed in which
objective testing of snoring was done before and after uvulopalatopharyngoplasty
(UPPP). Although the objective results demonstrated minimal improvements following
surgery, this finding did not correlate with the marked subjective improvement reported
by bed partners. In the past, objective testing lacked the ability to identify which
components of the snoring noise were most annoying to the human ear. Recently, new
devices have become available that appear to correlate more closely with subjective
reports. In a study that compared snoring before and after laser-assisted uvulopalatoplasty
(LAUP), a recording device was used to obtain objective data. The objective results with
this device compared favorably with the subjective responses of patients and bed partners
(1). As new procedures become available for the treatment of snoring, accurate objective
data will be essential in both assessing outcome and comparing results with more
standard treatments for snoring as well as documenting the significant improvement in
the quality of life in both patients and their partners that has been reported (2,3).
Obstructive Sleep Apnea
In the 1993 report of the National Commission of Sleep Disorders Research, it was
estimated that 20 million Americans experience excessive daytime sleepiness due to
sleep apnea. Certainly, subgroups such as commercial truck drivers have a much higher
prevalence of obstructive sleep apnea (OSA). In a recent study, 87% of a group of 156
truck drivers were found to have OSA. The most recent well-designed prevalence study is
the Wisconsin Sleep Cohort Study. After completing a questionnaire, a random sample of
602 employed men and women 30 to 60 years of age underwent a full polysomnogram in
a sleep laboratory. This study demonstrated that 24% of men and 9% of women had a
respiratory disturbance index (RDI) of 5 or more and 4% of men and 2% of women had
clinical symptoms as well as polysomnographic findings of OSA. This translates into
approximately 12 million Americans who have OSA, of which nearly one fourth
experience this disease at a moderate or severe level.
SLEEP PHYSIOLOGY
Normal Sleep
Familiarity with normal sleep physiology is essential to the surgeon who treats snoring
and OSA disorders. Without this basic knowledge, the results of a surgical procedure
cannot be evaluated. According to Carskadon and Dement (4), sleep can be defined as a
reversible behavioral state of perceptual disengagement from and unresponsiveness to the
environment. Another definition of normal sleep is the amount and quality of sleep
needed to maintain alertness throughout the day. Daytime fatigue may result from
volitional sleep deprivation, poor sleep quality, or a combination of these factors. One of
the most debated issues in sleep medicine today is whether our modern society as a whole
is sleep deprived.
An ideal night of sleep in a young adult averages between 7.5 and 8.5 hours. The
variation in the length of sleep varies from day to day and from person to person. Sleep
length is determined by genetic factors, circadian rhythms, and voluntary control. The
most significant determining factor of length of sleep in our society today is the alarm
clock.
Sleep has been divided into two distinct states: nonrapid eye movement (NREM) and
rapid eye movement (REM). These two states differ based on a constellation of
physiologic parameters associated with each state. NREM sleep is characterized by a
steady, slow heart rate and respiratory rate as well as low blood pressure. NREM is the
quiet stage of sleep. REM sleep, in contrast, is characterized by bursts of rapid
conjugate eye movement, increased autonomic activity, and dreaming. During REM
sleep, there are large fluctuations in the blood pressure, heart rate, and respiratory rate.
This stimulated state is combined with a decrease in muscular activity. REM can be
defined as a highly activated brain in a paralyzed body.
The pattern of sleep in the young, healthy adult remains fairly constant from night to
night. There appear to be minimal differences between the sleep of men and women in
this age group. Sleep onset begins in stage 1 NREM, a short stage that lasts only a few
minutes. The arousal threshold for this stage is very low; that is, a small noise can arouse
someone from this stage. Stage 2 NREM occurs next. This stage is characterized by sleep
spindles or K complexes on the electroencephalogram (EEG). This stage lasts anywhere
from 10 to 25 minutes and is considered a deeper stage of sleep compared with stage 1.
Stage 3 NREM sleep begins with high-voltage slow-wave activity being seen on the
EEG. This is a short stage, lasting only a few minutes, and then stage 4 NREM sleep
begins and usually lasts 20 to 40 minutes. The combination of stage 3 and 4 NREM sleep,
which have similar EEG activity, make up deep sleep, or delta sleep. Finally, sleep begins
to lighten, and stage 2 is entered, followed by either stage 1 or REM sleep. The initial
REM sleep period is short, often only a few minutes, but as the night progresses, REM
sleep time increases. In the young adult, NREM sleep occupies about 80% of the night,
and REM occupies the other 20% (Table 50.1).

TABLE 50.1. YOUNG ADULT NORMAL SLEEP
ARCHITECTURE



Throughout life, there is an evolution of sleep stage distribution. Young infants and
children have a higher percentage of REM sleep and stage 4 NREM sleep compared with
older children and adults. When children reach the age of 10, adult sleep patterns begin to
be observed. The elderly continue to have the same percentage of REM sleep as younger
adults, but the stage 4 NREM sleep diminishes dramatically. By the age of 60, stage 3/4
NREM sleep may no longer be present, especially in men. With the aging process,
women maintain slow-wave sleep longer than men.
Sleep-Disordered Breathing
Sleep disturbances range from self-limited sleep deprivation, which causes fatigue, to
OSA, which can result in fatal pulmonary and cardiovascular complications. In 1990,
these sleep disorders were organized in the International Classification of Sleep Disorders
(ICSD) by the American Sleep Disorders Association (ASDA). This replaced the
Diagnostic Classification of Sleep and Arousal Disorders, published in 1979. At present
there are 84 distinct sleep disorders listed in the ICSD manual. The 84 disorders are
divided into four major categories of sleep disorders: dyssomnias, parasomnias, medical
psychiatric sleep disorders, and proposed sleep disorders.
Snoring is classified as a parasomnia. Parasomnias are physical phenomena that occur
predominantly while sleeping and are considered undesirable. Parasomnias are
subclassified into four categories: arousal disorders, sleepwake transition disorders,
parasomnias associated with REM sleep, and other parasomnias. Snoring is categorized
as a parasomnia in the other category.
Obstructive sleep apnea syndrome (OSAS) is classified as a dyssomnia. Dyssomnias are
sleep disorders that produce excessive sleepiness. The dyssomnias are further divided
into three subcategories: intrinsic, extrinsic, and circadian rhythm sleep disorders.
Obstructive sleep apnea syndrome is classified as an intrinsic dyssomnia.
SLEEP DISORDERS
Our understanding of upper airway obstruction has evolved considerably over the past
three decades, and during this period clinical sleep research has progressed tremendously.
In the 1960s, the only upper airway closure syndrome described was OSA, in addition to
the sleep disorder of snoring. Three distinct syndromes now have been described: (a)
upper airway resistance syndrome (UARS), (b) obstructive sleep hypopnea syndrome
(OSHS), and (c) OSAS (Table 50.2). Each of these syndromes has a distinct definition,
yet all three have in common the symptom of excessive daytime sleepiness resulting from
repeated upper airway obstruction. These three disorders belong to a continuum of a
disease process that is based on the severity of the airway obstruction. Partial airway
obstruction initially presents as snoring, which then may progress to UARS, to OSHS,
and finally to OSAS. Yet the individual patient may not pass steadily through this
continuum; that is, a patient may snore for years and then go straight on to having OSAS,
depending on the severity of the upper airway obstruction. Each of these disorders
requires a polysomnogram to make the diagnosis.

TABLE 50.2. UPPER AIRWAY CLOSURE
SYNDROMES



A few basic definitions must be reviewed before each upper airway closure syndrome is
described. An apneic event is defined as cessation of ventilation for 10 seconds or longer,
which leads to an arousal. The definition of a hypopneic event varies from laboratory to
laboratory, but it usually is defined as a decrease in airflow in association with
oxyhemoglobin desaturation, which leads to an arousal from sleep. There are three
patterns of apnea: (a) obstructive, (b) central, and (c) mixed. An obstructive apneic event
is defined by lack of airflow despite ventilatory efforts. A central apneic event is defined
as the lack of airflow resulting from an absence of ventilatory effort. Finally, a mixed
apneic event is partially central and obstructive in nature. A mixed apnea usually begins
as a central apneic event and ends as an obstructive event (Fig. 50.1).

FIGURE 50.1. Polysomnographic tracing demonstrating
obstructive apnea, mixed apnea, central apnea, and
hypopnea.



Snoring
Snoring, an undesirable sound that occurs predominantly during sleep, is classified as a
parasomnia in the ICSD manual. Snoring is a disorder itself, but it is also a sign of
incomplete pharyngeal obstruction. Snoring is caused by changes in the configuration of
the upper airway during sleep. The snoring sound is believed to originate from the
collapsible portion of the upper airway. Although the uvula is often labeled as the
villain by bed partners of snorers, snoring may originate from the vibration of the soft
palate, tonsillar pillars, or even the base of the tongue. Patients who have undergone a
uvulectomy can still snore.
Snoring, usually described as a low-frequency noise that originates somewhere in the
upper airway, fluctuates in volume throughout the night as well as from night to night.
The site of snoring sound generation varies not only between patients but also within the
same patient. This heterogeneity of the airway makes snoring treatment complex.
Woodson et al. (5) examined the palatal specimens of severe apneics, snorers, and
nonsnorers and noted similar histopathologic changes in the snorers and apneic patients.
Both snorers and apneics had mucous gland hypertrophy, muscle bundle disruption,
atrophy of muscle fibers, and edema of the lamina propria with vascular dilation (5).
These changes lend support to the speculation that vibratory trauma to pharyngeal tissue
is an etiologic factor in both apnea and snoring.
Upper Airway Resistance Syndrome
In the sleep community, there is general consensus that there is a pathophysiologic
continuum in sleep-related upper airway closure syndromes. The mildest of these
syndromes is upper airway resistance syndrome, which was described by Guilleminault et
al. in 1993. A group of patients who reported excessive daytime somnolence but had
normal sleep studies was investigated. Initially, this group of patients was given a
diagnosis of idiopathic hypersomnolence. On further evaluation, the investigators noted
that these patients had repetitive alpha EEG arousals, which led to sleep fragmentation.
Esophageal pressure monitoring also was performed on these patients. This monitoring
demonstrated that patients with UARS had abnormally high negative intrathoracic
pressures. In patients with UARS, the increased effort required to generate the more
negative pressures results in an increase in the work of breathing and sleep arousals.
Repetitive sleep arousals, independent of etiology, have been demonstrated to cause
daytime fatigue even if the patient is not sleep deprived. UARS is associated with
crescendo snoring, although snoring does not occur in all patients. In contrast to patients
with OSAS, UARS is seen as frequently in women as in men, in nonobese patients, and is
more common in young adults than in elderly patients.
Obstructive Sleep Hypopnea Syndrome
Obstructive sleep hypopnea syndrome is associated with increased ventilatory effort and
excessive daytime sleepiness. In years past, a hypopnea was considered a less disruptive
respiratory event than an apneic event. Now most sleep laboratories consider apneas and
hypopneas to be physiologically equivalent in their ability to disrupt sleep. Thus, these
events are combined in a single value called the apnea hypopnea index (AHI) or the RDI.
The AHI or RDI includes the number of apneas plus hypopneas per hour of sleep. A
standard definition for a hyponeic event has not been established; thus, each sleep
laboratory may define a hyponeic event differently. The more common definitions
include a decrease in oronasal airflow of 30% to 50% for 10 seconds or longer
accompanied by a 3% to 4% decrease in blood oxygen saturation; the event is terminated
by an arousal. OSHS has been defined as having 15 or more hypopneas per hour and
associated with daytime sleepiness.
Obstructive Sleep Apnea Syndrome
Obstructive sleep apnea syndrome is a sleep disorder in which repeated events of
cessation of airflow or a reduction in airflow are accompanied by many symptoms,
including excessive daytime fatigue. Although there is no universally accepted definition
of OSAS, it is usually defined as an apnea index (AI) of 5 or more or an RDI of more
than 10. These criteria are based on a young adult population, and in recent years it has
been recognized that a healthy elderly person may have more than five apneic events per
hour without any clinical consequences. Thus, where normal sleep ends and mild OSA
begins varies depending on the patient's age and the definition of the individual sleep
laboratory.
Obstructive sleep apnea has been divided into three severity levels based on the RDI. In
addition to the RDI, the level of hypoxemia associated with the sleep-disordered
breathing events also is categorized into three distinct levels (Table 50.3). The amount of
desaturation accompanying a specific sleep-disordered breathing event is influenced by
the patient's functional residual capacity, oxygen stores, length of the sleep-disordered
breathing event, and the baseline awake saturation level.

TABLE 50.3. CLASSIFICATION OF SLEEP
APNEA AND HYPOXEMIA SEVERITY



PHYSIOLOGY OF UPPER AIRWAY OBSTRUCTION
The pathogenesis of obstructive sleep apnea and hypopnea syndromes has received
considerable attention. Despite this interest, only fragmentary knowledge of the
abnormalities that underlie closure of the upper airway is available. There are three
fundamental features that appear generally accepted: (a) upper airway obstruction occurs
in the pharynx; (b) the pharyngeal lumen size is determined by a balance of forces
between the constricting forces of the negative intrathoracic pressure generated by the
diaphragm and the dilating forces of the pharyngeal dilating muscles; and (c) anatomic
abnormalities that contribute to pharyngeal narrowing are present in many patients with
OSAS. In the 64 OSAS patients studied during sleep, 81% had collapse at the level of the
nasopharynx, with 75% having more than one site of obstruction in the airway. This
finding of collapse at multiple levels is significant and helps explain why correction of an
obstruction at one level is usually not adequate in the treatment of apnea.
Abnormal neuromuscular control of the pharyngeal dilators is thought to contribute to the
collapse of the airway. The medial pterygoid, tensor veli palatini, genioglossus,
geniohyoid, and sternohyoid muscles are all considered pharyngeal dilator muscles. The
reflex activation of the dilator muscles in response to airway obstruction often fails in
patients with OSAS. This failure of the reflex to activate has been attributed to defects in
the ventilatory control in apneic patients, delay in the activation of the reflex, and defects
in the arousal mechanisms. Thus, there appears to be a failure to dilate the airway in
many OSAS patients during sleep, which leads to upper airway instability and collapse.
Anatomic narrowing of the pharynx at any level contributes to collapse of the airway.
Because greater inspiratory pressures are needed to generate airflow the smaller the
diameter of the airway, an anatomically narrowed pharynx is more vulnerable to collapse
than a wider pharynx. The anatomic abnormalities commonly seen on physical
examination in patients with OSAS include soft palate elongation, retrognathia, tonsillar
or adenoidal hypertrophy, macroglossia, and micrognathia (Fig. 50.2). Cephalometric
data and acoustic reflection studies both demonstrate objective evidence of skeletal and
soft-tissue airway narrowing in patients with OSAS.

FIGURE 50.2. Levels and sites of possible airway
obstruction in patients with sleep disorders.



CLINICAL EVALUATION OF THE SUSPECTED SLEEP APNEA
PATIENT
History
The initial evaluation of a patient who is suspected to have sleep apnea should include
input from the bed partner or family. The patients are often unaware of their nocturnal
symptoms of apnea and usually are made aware of the problem by their bed partner or
when symptoms begin to affect their daytime performance. This impairment of daytime
functioning usually manifests itself over a prolonged period; therefore, patients adjust
their life-styles to accommodate their fatigue. It is often the family or employer who first
comments on the daytime sleepiness. In reality, it is the bed partner who, in most cases,
insists that the patient seek medical care despite protests by the patient.
The initial evaluation process should include a detailed sleep history, a directed physical
examination, and education of the patient and the patient's family. At the initial visit, a
patient-friendly educational video or pamphlet should be reviewed before the patient is
evaluated by the physician. This sequence allows the patient and family some time to
reflect on the disease process and to compare it with the sample patient used for
educational purposes. Following the educational process, a sleep questionnaire is
completed. The sleep history should review (a) bedtimes, (b) arousal times, (c)
awakening times, (d) body position during sleep, (e) restless sleep, (f) alcohol or sedative
use, (g) caffeine intake, and (h) mouth breathing at night.
The most common presenting signs and symptoms of sleep apnea are snoring and
daytime sleepiness. Sleepiness is a subjective complaint and may be influenced by a
number of factors. Sleepiness can be evaluated more objectively by the Epworth
Sleepiness Scale or the Standford Sleepiness Scale. Both of these commonly used scales
ask patients to rate their level of fatigue in various situations and then give a total score
for sleepiness. These scales can be incorporated into the initial questionnaire. Other signs
and symptoms can be divided into nocturnal and daytime events.
In addition to signs and symptoms, there are patient characteristics that are associated
with sleep apnea. The more common characteristics include male sex, advancing age,
truncal obesity, large neck circumference, and hypertension (Fig. 50.3). Al-though all
these characteristics are associated with sleep apnea, the predictive value of each
individual or a group of characteristics remains suggestive at best (Table 50.4).

FIGURE 50.3. A patient with obstructive sleep apnea.



TABLE 50.4. DIAGNOSIS OBSTRUCTIVE
SLEEP APNEA



Physical Examination
The physical examination of the snoring or sleep apnea patient should include a complete
examination of the head and neck, including flexible endoscopic examination. An
examination looking for possible medical sequelae of apnea, such as hypertension and
congestive heart failure, are also mandatory. All patients should have a complete set of
vital signs taken, a body mass index calculated (the weight in kilograms divided by the
square of the height in meters), and neck circumference (measured at the cricothyroid
membrane) or shirt-collar size recorded at the initial visit. If obesity exists, the pattern of
obesity should be noted. Truncal or central obesity is known to be associated with
nocturnal breathing disorders. Vital signs and weight are checked at each visit. Patients
suspected of having severe apnea should also be checked for pedal edema.
A complete head and neck examination is performed. The airway must be examined
closely for areas of obstruction or disproportionate anatomy. The examination of the
airway can be divided into an examination of the skeletal and soft tissue abnormalities. In
the vast majority of patients with known sleep apnea, one specific anatomic focus of
pathology will rarely be identified. Often an underlying skeletal narrowing combined
with pharyngeal soft-tissue excess or neuromuscular compromise result in a
dysfunctional airway at night. It is important to recognize that there are no stereotypical
physical traits that guarantee airway collapse. In general, an overweight 50-year-old man
is much more likely to have sleep apnea than a thin 20-year-old woman. Yet, a physical
examination of the airway of each patient is essential before ordering a polysomnogram.
A young woman who is retrognathic and has tonsillar hypertrophy may be more likely to
have sleep apnea than a man whose cra-niofacial skeletal structure is normal and his
tonsils absent.
The head and neck examination can be performed in any order, but a routine is
recommended. Initially, the nasal cavity can be examined anteriorly with a speculum,
followed by a more complete examination with a flexible endoscope. The nasal
examination should be performed with and without decongestants. A nasal septal
deviation, nasal polyps, turbinate hypertrophy, and nasal valve collapse are among the
common causes for nasal obstruction. The oral cavity should be examined using a tongue
blade and looking at the overall size, shape, and length of the hard and soft palates,
evaluating the position and size of the tongue, and noting the size of the tonsils, if
present. Tongue size, tonsil size and the body mass index (BMI) have been shown to be
significant predictors of OSA (6). The neck should be assessed for overall size and shape,
lymphadenopathy, and thyroid abnormalities. Often the neck is quite obese in patients
with sleep apnea and therefore palpation may not disclose any pathology. Diagnostic
imaging such as ultrasonography or computed tomography (CT) scan may be essential in
the obese neck.
Flexible endoscopic examination of the entire airway should be performed in every
patient. Laryngeal, nasopharyngeal, and base-of-tongue tumors can present as new-onset
snoring in a patient who never snored. This examination can be performed while the
patient is seated or supine. Often a small amount of local anesthesia is used before the
introduction of the scope to make the procedure more tolerable. First, a general
examination of the larynx, hypopharynx, oropharynx, nasopharynx, and posterior nasal
cavities is performed. Next, the velopharyngeal valve should be examined for its closure
pattern. Two different patterns of closure may be observed: a coronal pattern, in which
there is anteroposterior movement of the velum, as opposed to a circular pattern, in which
there is medial movement of the pharyngeal walls. A Mller maneuver then is performed
at the level of the base of the tongue and just above the velopharyngeal valve by asking
the patient to inspire with a closed oral and nasal cavity while the flexible scope is in
place. The pattern and degree of collapse are evaluated at each level. Because the Mller
maneuver is dependent on the patient's effort, it should be repeated a few times at each
level. Many grading systems exist that give a score or category to describe the degree of
collapse of the airway. No standardization exists for these grading systems; so it may be
preferable simply to describe the amount of the collapse at each level of the pharynx.
RADIOGRAPHIC EVALUATION
A variety of imaging techniques have been used to evaluate the structural and functional
properties of the upper airway in patients with suspected or known sleep apnea. These
techniques include (a) cephalometric roentgenograms, (b) CT, (c) magnetic resonance
imaging (MRI), and (d) somnofluoroscopy. These modalities have been used as
investigational tools to increase our understanding of the physiologic behavior of the
upper airway as well as to give clinical information in the individual patient. Other
techniques such as manometry and acoustic reflection are used primarily for research
studies at this time.
Cephalometric Roentgenograms
Cephalometric roentgenograms are inexpensive, readily obtainable, two-dimensional
static images of the upper airway taken with the patient awake and in an upright position.
Whether cephalometric roentgenography should be a routine preoperative study is highly
debated. Specific landmarks are identified and used to measure certain airway spaces and
relationships of skeletal structures. The soft tissue anatomy is also examined, although
cephalometry is used primarily to evaluate the bony anatomy. Numerous investigators
have demonstrated that certain craniofacial patterns are commonly seen in association
with OSAS. Among the more commonly identified abnormalities in the OSAS patient are
(a) retrognathia, (b) a narrowed posterior airway space, (c) an increased mandibular plane
to hyoid bone distance, (d) a shortening of the anterior cranial base, and (e) an enlarged
soft palate. Analysis of the upper airway bony structure has given rise to the theory that
certain persons have favorable craniofacial structure and tolerate obesity without
developing sleep apnea, whereas patients with unfavorable craniofacial structure can
have sleep apnea in the absence of obesity. Patients with normal dental occlusion may
tolerate obesity better than patients with retrognathia or a small posterior airway space.
Computed Tomography and Magnetic Resonance Imaging
Computed tomography is an excellent method for evaluating the upper airway because it
provides detailed anatomic viewing and is noninvasive. It allows for quantitative
measurement of upper airway cross-sectional area, tongue size, and palate size. Recently,
fast-CT scanning, which requires a shorter scanning time and therefore a lower radiation
dosage than conventional scanning, has been used to examine the airway in the awake
and sleeping patient. The disadvantages of CT scanning are the radiation exposure,
expense, and relevance of the information obtained in the clinical practice of sleep apnea
medicine.
Magnetic resonance imaging also offers detailed anatomic information in a noninvasive
manner without exposure to ionizing radiation. One of the advantages of MRI over CT is
the ability of MRI to image directly in multiple planes. With computer-based imaging,
three-dimensional displays of the airway can be obtained. The drawbacks to MRI are the
long time required to obtain an image and the high cost. MRI is presently being used as a
research technique but is not commonly part of the clinical evaluation of a patient with
sleep apnea.
DIAGNOSTIC STUDIES
Various sleep scales rate the amount of daytime sleepiness and are used to determine
which patients should proceed to polysomnography. The two most commonly used scales
are the Epworth Sleepiness Scale and the Standford Sleepiness Scale. Both are useful
adjuncts to an initial evaluation of a patient and can be used to monitor patient symptoms
while they are receiving treatment, but neither can predict apnea with great certainty. The
combination of symptoms and patient characteristics that could predict who needs a
polysomnography have been evaluated by many investigators. The combination of
daytime sleepiness, habitual snoring, observed apnea, and nocturnal gasping is a strong
predictor of clinically significant sleep apnea. In a group of patients who presented for
LAUP, 850 patients were evaluated to determine whether clinical signs and symptoms
could predict apnea, thereby allowing a physician to reduce the number of patients
referred for polysomnography before this outpatient procedure. The results from two
models of regression analysis selected an increased BMI, observed apnea, falling asleep
while driving, male gender, and increasing age as significant predictors of sleep apnea.
Although all these factors are associated with OSAS, there remains no set group of
symptoms or patient characteristics that can rule in or rule out sleep apnea with certainty
(7).
Diagnostic testing for OSA ranges from the gold standard of attended polysomnography
in a sleep laboratory to tape recordings of nocturnal breathing performed at home by the
patient. Polysomnography is a comprehensive study used to diagnose a wide spectrum of
sleep disorders. Both sleep and cardiopulmonary variables are evaluated extensively
during polysomnography. Because of current economic imperatives, less costly but
efficacious alternatives have been pursued avidly. Some of these alternatives are being
used as screening devices to target which patients need an in-depth evaluation; others are
being used to replace conventional sleep laboratory testing.
Oximetry
Nocturnal oximetry has been used as a screening device for sleep apnea. Although
oximetry alone has significant limitations, it can be used in conjunction with other testing
to screen patients for less invasive operative procedures such as LAUP.
Several studies have looked at nocturnal oximetry and, depending on the parameters
chosen, oximetry can have a sensitivity as high as 100% and a specificity as high as 98%.
Gyulay et al. (8) suggest that if the percentage of time spent with a Sao
2
below 90% was
less than 1% of the sleep time, clinically significant apnea is practically excluded.
Acoustic Recording Devices
In the pediatric population, the parents of patients with tonsillar or adenoidal hypertrophy
are often asked to record the respiratory sounds of their child while the child is asleep.
This recording is given to the physician, who listens for a few minutes for apneic periods.
The accuracy of these recordings in the prediction of apnea depends on many factors and
remains questionable. More sophisticated devices are now available that record oronasal
respiratory sounds at a fixed distance for the oral cavity and nose.
Portable Polysomnography
Home sleep studies, also known as portable studies, recently became available as an
alternative to studies performed in a sleep laboratory. The cost of portable studies, the
convenience, and the familiar atmosphere for the patient are all advantages over
traditional testing. In 1994, the ASDA published specific recommendations in a practice
parameters paper on the use of portable polysomnography. This review clearly states that
a standard overnight polysomnogram in a sleep laboratory is the accepted diagnostic
method for the diagnosis of OSA. Portable studies can be used when standard studies are
not readily available, for patients who need to be studied at home, and to evaluate the
result of therapy.
Polysomnography
A standard polysomnogram records (a) an EEG, (b) an electrooculogram, (c) an
electrocardiogram (ECG), (d) an electromyogram (EMG), both submental and anterior
tibialis, (e) oxyhemoglobin saturation, (f) nasal or oral airflow, (g) thoracic/abdominal
movement, (h) sleep position, and (i) blood pressure. Some laboratories also record
esophageal pressure to assess breathing efforts. All this information is reviewed and
reported in a sleep study report. The report should address the (a) sleep latency (length of
time to fall asleep); (b) sleep efficiency (total sleep time/time in bed); (c) RDI; (d) types
of respiratory disturbances as well as the average and maximum length of each event
type; (e) sleep architecture; (f) volume and presence of snoring; (g) effect of position on
the respiratory disturbances; (h) whether the respiratory disturbances occur more often in
particular sleep stages; and (i) number and severity of the oxygen desaturation events as
well as the total amount of time with an abnormal oxygen saturation level.
Often it is difficult to sort out what information is important when evaluating a patient for
a surgical procedure. The most important factors frequently cited in surgical publications
are the RDI, the lowest Sao
2
for the night as well as the length of time with an oxygen
saturation below 88%, and the ECG findings. These three parameters give the surgeon a
good picture of the severity of the apnea when determining treatment options.
It is also important to be aware that two types of studies can be performed: full-night
versus split-night. A full-night study is a baseline recording for the entire night; no
treatment is instituted. Often cited as an advantage of a full-night study as opposed to a
split-night study, the length of the recording without intervention in a full-night study
allows for a more accurate reflection of the severity of the apnea. Sleep apnea is often
worse during the second half of the night. Thus, a split-night study may not accurately
assess the severity of the apnea because only 1 or 2 hours at the beginning of the night are
recorded before nasal continuous positive airway pressure (CPAP) is begun. In addition,
during a full-night study, all positions may be assessed adequately. Data supporting split-
night studies have demonstrated that the RDI in the first part of the night is predictive of
the second half of the night in most patients and that the majority of patients could be
adequately titrated in the first night. Data against a split-night study show that compliance
with nasal CPAP is less and as many as one quarter of patients require readjustment of
their nasal CPAP pressures after a split-night study.
Multiple Sleep Latency Test
A multiple sleep latency test (MSLT), also referred to as a nap study, is used to measure
daytime sleepiness objectively. The patient is given four or more opportunities to nap
throughout a day at 2-hour intervals, and the latency to sleep onset and REM sleep is
evaluated. An MSLT is not necessary to diagnose OSAS. This test is more commonly
used to document sleepiness in a patient with a normal polysomnogram. It also has been
used by certain industries, such as the trucking or aviation industries, to document an
individual's daytime sleepiness.
PREOPERATIVE MEDICAL EVALUATION OF PATIENTS WITH
OBSTRUCTIVE SLEEP APNEA SYNDROME
Once a diagnosis of OSAS is established, a medical evaluation of the patient is
mandatory prior to planning a surgical intervention. All factors that may predispose or
exacerbate upper airway obstruction that are correctable should be addressed in the
preoperative period. An example would be weight loss; even a moderate loss of 10 to 15
pounds may improve the severity of the apnea significantly. Thus, comorbid factors,
including cardiac arrhythmias, congestive heart failure, systemic hypertension,
hypothyroidism, obesity, and esophageal reflux require attention whether a surgical
treatment or medical treatment plan is chosen.
Cardiopulmonary Disease
Cardiopulmonary disease can be exacerbated by OSAS, result from OSAS, and increase
the severity of OSAS. Often the initiation of nasal CPAP will bring improvement in
hypertension control, congestive heart failure, and pulmonary hypertension. Long-term
studies have demonstrated that hypertensive patients show a decrease in mean blood
pressure with CPAP treatment that was not seen in normotensive patients; however, some
of the benefit may relate to other interventions, such as weight loss.
Cardiopulmonary disease is so prevalent in patients with moderate or severe apnea that a
complete evaluation is necessary in most patients, especially if a surgical procedure is
contemplated. Systemic hypertension has been found in about 50% of OSAS patients,
pulmonary hypertension has been found in 10% to 20%, and cardiac arrhythmias also are
frequently noted in this population. A preoperative evaluation by the primary care
physician is essential in many of these patients, and routine postoperative follow-up is
also needed. If the apnea is successfully resolved following surgical intervention, patients
often need their antihypertensive medications readjusted in the postoperative period.
Hypothyroidism and Acromegaly
All newly diagnosed patients should be routinely evaluated for hypothyroidism. Although
the incidence of hypothyroidism in patients with sleep apnea is not well established, a
screening for thyroid-stimulating hormone (TSH) is inexpensive. Several studies indicate
that thyroxine replacement reverses the apnea frequency independent of changes in
weight and pulmonary function. Thyroid hormone replacement must be performed
gradually and in combination with treatment of the apnea to avoid cardiovascular
complications. Another endocrine disorder that has been associated with sleep apnea is
acromegaly. Acromegaly is much less common than hypothyroidism, so routine
screening is not recommended. If the patient has noted an increase in the size of his or her
hands or feet, changes in facial appearance, or other signs or symptoms of acromegaly, an
evaluation is warranted. Following treatment for acromegaly, the severity of the OSA
often improves. Thus, most patients with acromegaly should be started on nasal CPAP.
After the acromegaly has been treated, a repeat polysomnogram is warranted.
Obesity
Obesity is not a prerequisite for OSAS, but there is a high prevalence of obesity in this
patient population. About one third of the U.S. adult population is overweight. Obesity is
defined as a weight at least 20% more than ideal body weight. Above a BMI (the
weight in kilograms divided by the square of the height in meters) of 27, mortality
sharply increases. The male distribution of weight gain is different from that seen in
females. Men often gain most of their weight in the truncal region. This pattern of obesity
is more closely associated with OSAS and other respiratory diseases than weight gain in
the lower extremities.
Weight loss is associated with an improvement in apnea in most patients. Most patients
have a trigger weight above which apnea occurs or becomes clinically symptomatic. It
is well established that a large weight loss improves apnea severity and even a moderate
weight loss is associated with an improvement. Weight loss methods include behavior
modification with low-calorie diets combined with exercise programs, medications, and
bariatric surgery. It appears that regardless of the means to reduce body weight,
recidivism is high in patients who do lose weight. A complete life-style change, which
includes the introduction of exercise, is needed to maintain weight loss over time. Thus,
long-term follow-up of these patients is necessary to help motivate the patient and to
begin further treatment if there is an exacerbation in the apnea due to weight gain.
Other Disorders Associated with Obstructive Sleep Apnea Syndrome
Other diagnostic studies may be helpful if clinically warranted. Some of the more
commonly associated disorders seen in apneic patients include pulmonary dysfunction
and gastro-esophageal reflux. Evaluation of these disorders and subsequent treatment
may be of value in the treatment of the individual patient's apnea. It is essential that
apneic patients quit smoking for many reasons. Another treatable disease entity,
esophageal reflux, may cause significant mucosal irritation and can exacerbate apnea.
Reflux precautions, such as elevation of the head of the bed, antacids, and H
2
blockers or
proton pump inhibitors may be of great benefit to an apneic patient. In addition,
lengthening one's bedtime and a regular sleep pattern will benefit OSA patients. Finally,
it is important to stress to patients that decreasing or eliminating caffeine, tobacco, and
alcohol is necessary, and apnea should improve if these factors are controlled.
APPROACH TO TREATING SNORING AND OBSTRUCTIVE SLEEP
APNEA SYNDROME
Indications for Treatment
Although clinicians generally agree on the definition of OSAS, the actual decision to treat
must be individualized. Factors that need to be taken into account include severity of the
signs and symptoms, the patient's underlying cardiopulmonary function, and results of
polysomnography. Asymptomatic patients are often less enthusiastic and less compliant
than patients with daytime complaints. Whether asymptomatic patients with mild apnea
should be treated is debatable. According to outcome data, an AI score greater than 20 is
associated with increased mortality; thus, most physicians recommend that even
asymptomatic patients with these findings should be treated. In addition, in the presence
of risk factors for cardiac disease, such as cigarette smoking, hypertension, or an elevated
cholesterol level, patients with even mild apnea can benefit from treatment. Thus, the
decision to treat mild apnea must be based on the effect of the OSAS on daytime
functioning and baseline cardiopulmonary function rather than on the actual number of
abnormal respiratory events found on polysomnography. All patients with moderate or
severe apnea should be treated regardless of their symptoms.
Of course, the decision to treat also must take into account the available options and risks
involved with treatment. If the treatment option is associated with a minimal
complication rate, it may be reasonable to perform in even mildly apneic patients or
patients with nonapneic snoring, for example, in a patient who presents for treatment of
snoring and is found on evaluation to have mild OSA. This patient is asymptomatic with
regard to apnea. In this patient, no treatment or only treatment for the snoring, which may
or may not alter the apnea, may be reasonable. If the patient's presenting complaint is
daytime fatigue or if he or she has risk factors for cardiac disease, treatment of the apnea
is necessary.
Behavioral Treatment for Snoring and Obstructive Sleep Apnea Syndrome
Behavioral treatment options for snoring and OSAS patients are reasonable to consider in
most patients. Weight loss, avoidance of alcohol and medications that cause sedation, and
elimination of tobacco and caffeine from one's daily routine are all known to be of benefit
to the treatment of these disorders. Despite the short-term efficacy of weight loss, it is
commonly recognized that long-term maintenance of weight loss is poor. For this reason,
behavioral treatment should be considered adjuvant treatment while more immediate
effective treatment options are begun. Many patients benefit from a 1- to 3-month period
of nasal CPAP therapy combined with weight loss or elimination of exacerbating habits
or both in preparation for a surgical procedure.
This scenario allows the patient a chance to begin changing habits while being treated. In
addition, the patient is often quite motivated in the preoperative period and will accept
the nasal CPAP mask more readily if it may be a temporary intervention that helps to
prepare for surgery.
Nonsurgical Treatment of Snoring and Obstructive Sleep Apnea Syndrome
Nonsurgical treatment includes nasal CPAP therapy (Fig. 50.4) and various appliances.
Nasal CPAP therapy is almost never used for nonapneic snoring, but it may be a more
cost-effective alternative than separate bedrooms or divorce in patients who have failed
all other types of treatment. Alternatively, numerous oral appliances, nasal splints, and
positioning devices have been demonstrated to be effective in the treatment of snoring
and OSAS.

FIGURE 50.4. Continuous positive airway pressure
(CPAP) by nasal mask. A: The negative pressure
associated with inspiratory effort results in collapse at the
level of the soft palate and base of the tongue (arrow). B:
With application of a critical amount of CPAP, the
airway remains stented open.



An oral appliance is the generic term for any device inserted into the mouth at night for
the purpose of altering the position of the mandible or tongue to relieve snoring or sleep
apnea. There are essentially two categories of oral appliances. One is designed to advance
the mandible, known as a mandible (or jaw) advancement device (MAD). The other
device keeps the tongue in an anterior position during sleep by means of negative
pressure in a plastic bulb and is known as a tongue-retaining device (TRD). In the review
article and practice parameters paper issued by the ASDA on dental appliances, snoring
was found to be improved in almost all patients and eliminated in as many as 50% of
patients using oral devices. Although most studies obtained subjective data from patients
or bed partners, one study objectively documented improvement in snoring with a MAD.
The data on long-term compliance are limited, but in three papers in which compliance
was addressed, the range was 100% to 52%, and some patients had follow-up for more
than 3 years. This review by the ASDA concludes that oral appliances are a useful
treatment option in patients who snore.
Other nonsurgical treatment options for snoring and OSAS can include positioning
devices or nasal splints. It is well established that snoring is often less severe if the
patient sleeps in any position other than supine. There are many different types of
positional devices; the most popular is a T-shirt with tennis balls sewn into a pocket on
the back, which keeps the patient from sleeping on his or her back. In addition, there are
many forms of nasal splints, such as dilating nasal Band-Aids or internally placed coils,
that dilate the nasal vestibule. The efficacy for snoring of each of these devices is not
well documented, but certainly these devices are minimally invasive and may benefit
certain patients and thus are reasonable to investigate.
Surgical Treatment for Snoring
Surgical options presently include palatal surgery, tonsillectomy, adenoidectomy, and
nasal surgery. The more commonly performed surgical procedures for snoring are UPPP,
LAUP, and functional nasal surgery. Tonsillectomy and adenoidectomy may be
performed in a young adult, especially if tonsillar or adenoidal hypertrophy are present
and the patient snores habitually. Many of these young adults also have apnea associated
with their snoring.
Palatal surgery is the most commonly performed surgery for nonapneic snoring in the
adult. The UPPP operation was originally described by Dr. Ikematsu in the 1950s. Dr.
Ikematsu's first patient was a young woman who snored. Only in the 1980s was this
procedure introduced by Dr. Fujita in the United States as a treatment option for apnea.
Thus, the UPPP, originally a procedure for snoring, has been the mainstay of surgical
treatment for snoring. In 1993, LAUP was introduced in France by Dr. Kamami as an
alternative palatal procedure for the treatment of snoring. Initially, this procedure
generated great controversy in the sleep community. Thousands of patients who snored
presented to otolaryngologists, not sleep clinics, for this promising procedure to treat
their snoring. The evaluation prior to performing this office-based procedure was not
uniform. Only limited outcome data by Dr. Kamami were available when the procedure
was popularized. Thus, the ASDA committee felt strongly that practice parameters for
LAUP needed to be published. This publication, published in 1994, should be reviewed
before performing LAUP (9). At this time, office-based palatal surgery (either LAUP or
the many other nonlaser forms of this surgery, including the recently developed
radiofrequency tissue ablation technique) is the preferred treatment by most surgeons for
nonapneic snoring (10).
Descriptions of tonsillectomy, adenoidectomy, septoplasty, and turbinate cautery can be
found in many standard surgical textbooks. A brief description of UPPP and LAUP is
reviewed. Numerous techniques and modifications have been described for the UPPP,
which is performed with the patient under general anesthesia. If tonsils are present, they
are excised. Next, the uvula and inferior portion of the soft palate are excised, and the
tonsillar pillars are reoriented to enlarge the retropalatal airway. UPPP is performed in
one session (Fig. 50.5); LAUP is usually performed in the doctor's office with only local
anesthesia. Lidocaine with epinephrine is injected above the base of the uvula and 1 cm
lateral to the midline in the inferior portion of the soft palate. Bilateral vertical incisions
are made in the soft palate, followed by partial vaporization of the uvula with a CO
2
laser
(Fig. 50.6). There are numerous techniques and modifications of this procedure. Each
patient requires between one and five laser procedures, spaced approximately a month
apart, to complete treatment. Dr. Kamami and others also have performed LAUP in one
step.

FIGURE 50.5. Uvulopalatopharyngoplasty. Resection of
the palate is usually distal to the natural dimple or crease
that marks where the soft palate approximates the
posterior pharyngeal wall. A box-shaped palatal excision,
with removal of tissue above the superior pole of the
tonsil, results in a greater tendency to enlarge the
oropharyngeal airway by anterior displacement of the
sutured soft palate.



FIGURE 50.6. Laser-assisted uvulopalatoplasty. A:
Preoperative examination. B: Vertical trenches are
created. C: Uvula ablation. D: Postoperative examination
following one LAUP session.



Response rates, cost, and associated complication rates are important in determining
which procedures are performed for snoring. The short-term success rates of UPPP to
relieve or eliminate snoring range from 76% to 95%; however, in a landmark publication,
Levin and Becker (11) demonstrated that even if the initial results of UPPP for the
treatment of snoring are good (in their series the short-term success rate was 87%), after
12 months the success rate decreased to 46% (11). LAUP has had short-term success
rates similar to those obtained from UPPP (i.e., 77% to 89%). Long-term subjective
results are reported in one patient series that indicate that 75% of OSAS patients had
resolution of their presenting complaints and 52% had no snoring (12). The cost of LAUP
is at least one third to one half the cost of UPPP. The overall complication rate for LAUP
was 3.5% in a series of 275 patients who underwent 754 LAUP procedures. All these
complications were minor and resolved without treatment, except for bleeding that
required medical attention in 1.3% of the procedures. These complications compare
favorably with those of UPPP (13).
Nasal surgery is also performed in patients who snore and have significant nasal
obstruction. Patients whose snoring is mainly nasal in origin may have a severe septal
deviation, nasal turbinate hypertrophy, or nasal polyps.
Often patients who snore have multiple levels of partial obstruction contributing to the
snoring noise. In what order procedures should be performed is a question that always
arises. Generally, it makes sense to perform the least invasive procedure with the best
outcome first, followed by more involved procedures; however, each case must be
individualized based on the patient's presenting complaints and physical examination. Of
course, cost issues, patient convenience, and time off from work all factor into a practical
treatment plan. In patients with a severe nasal obstruction, it is best to take care of the
nasal obstruction first. If the patient continues to snore, LAUP or UPPP may be
considered in the future. In general, a waiting period of at least 3 months is necessary to
assess the outcome of one procedure before initiating another procedure. Finally, if the
patient needs nasal surgery, which is performed under general anesthesia or with
intravenous sedation, and requests a timely resolution to the snoring problem, a
simultaneous palatal procedure may be a reasonable option. The patient then would
require only one postoperative healing period. Many patients prefer to have surgery under
general anesthesia as opposed to being awake in the doctor's office (Table 50.5).

TABLE 50.5. TREATMENT NONAPNEIC
SNORING



SURGICAL TREATMENT OF OBSTRUCTIVE SLEEP APNEA
SYNDROME
Surgical treatment is an important option, and in many cases the best option, for patients
with OSAS. Certainly, nasal CPAP or BiPAP are effective; however, the concern remains
that long-term compliance is not obtained in as many as 75% of patients who use this
device. Compliance is not an issue in surgically treated patients. Young patients and
patients with mild or moderate apnea are much more likely to refuse nasal CPAP or
BiPAP and prefer surgical treatment.
When considering surgical treatment for a patient with OSAS, it is important to
remember that few of these patients have a specific space-occupying mass. On occasion,
a patient will present with only massive tonsillar hypertrophy and will be cured by a
tonsillectomy. More commonly, patients with OSAS have disproportionate anatomy.
Thus, surgery is performed to alter the anatomy in a favorable fashion. In general,
enlargement of the retropalatal, retrolingual, or both airway spaces will improve airflow.
Certain procedures modify soft tissue structures, and others alter skeletal anatomy. These
procedures can be performed individually, synchronously, or sequentially, depending on
many factors.
Presently five categories of procedures can be performed to enlarge the upper airway in
apneic patients: (a) nasal surgery, (b) palatal surgery with or without tonsillectomy, (c)
tongue base reduction surgery, (d) maxillomandibular surgery, and (e) tracheotomy. Each
of these categories of surgical procedures can be used, depending on the individual
patient's anatomic findings, to relieve partially or completely the obstruction of airflow.
Fractional improvement can offer significant health benefits to patients. For example, a
septoplasty or nasal polypectomy may allow a patient to tolerate nasal CPAP or reduce
the level of apnea to the point that a dental device or positional device may be all that is
necessary to rid the patient of apnea (Table 50.6).

TABLE 50.6. TREATMENT OBSTRUCTIVE
SLEEP APNEA



Anesthetic Management of Patients with Obstructive Sleep Apnea Syndrome
Patients with OSAS present a significant challenge for the anesthesiologist. Management
of this type of patient begins when a surgical procedure is elected. Many apneic patients
with moderate or severe apnea require a presurgical cardiac evaluation. Patients should
be asked to remain on nasal CPAP until the day of surgery. If a patient has severe apnea
and has refused nasal CPAP in the past, convincing the patient to use this device for 1
month before surgery would be of great benefit. Severe apneics who are not wearing
nasal CPAP have more airway edema, may have mild congestive heart failure with fluid
retention, and have a greater tendency to develop postobstructive pulmonary edema
because of the acute relief of the obstruction. The patient also should be asked to quit
smoking and give weight loss one final attempt in the month or two before surgery.
Patients with OSAS are considered difficult airway cases because many of them have
retrognathia, a small oral cavity, marked pharyngeal soft-tissue redundancy, and relative
macroglossia and are obese. When a patient's airway is deemed difficult and an awake
intubation is anticipated, explaining this procedure to the patient in advance helps to
prepare the patient mentally. Finally, before surgery, absolutely everyone, including the
patient, must be aware that no preoperative sedation is allowed. The patient must be in an
operating room, which is prepared for an airway emergency, and an anesthesiologist and
surgeon should be present before sedation is begun. Jet ventilation, a tracheotomy tray,
and oral/nasal airways all should be readily available in the operating room.
The advent of fiberoptic laryngoscopy has improved airway management in patients with
OSAS dramatically. In addition, transtracheal high-frequency jet ventilation is a valuable
device that can be used to manage the airway when necessary. Of course, the most
important factor is a skilled anesthesiologist who is willing to work with the surgical
team. The surgeon must be educated as to which anesthetic choices are preferable in
apneic patients, the technique of fiberoptic intubation with transtracheal placement of
local anesthesia, as well as emergence stages from anesthesia so that the patient is not
extubated prematurely. Most apneic patients are obese and have slowed gastric emptying
as well as reflux; thus, the stomach should be emptied before extubation. Ultimately, if
the airway is lost, an emergent cricothyrotomy or tracheotomy would need to be
performed. This is not a minor task in a patient with no pulmonary reserve and an obese
neck. Thus, tremendous emphasis should be placed on a safe, secure intubation. Most
airway emergencies occur postoperatively and can be fatal. Intraoperative avoidance of
opiates, use of high-dose perioperative steroids, extubating only when the patient is wide
awake with good muscle tone, and performing a temporary tracheotomy before
extubation when the airway is judged to be unstable or intubation was difficult are all
methods that will help make extubation safer.
Finally, the patient must be closely observed in the recovery room for a minimum of 1 to
2 hours. The patient should have the head of the bed elevated 60 degrees or more and
have continuous pulse oximetry; a nasal airway can be of great benefit following surgery.
Opiates and high concentrations of oxygen should be kept to a minimum to avoid
reduction of the respiratory drive. The patient also should be watched carefully for the
development of postoperative pulmonary edema in the first few hours following surgery.
Most patients need close monitoring in an intensive care unit or monitored bed for at least
24 hours. The level of observation depends on the patient's preoperative medical
condition and apnea severity, the surgical procedures performed, and the level of nursing
supervision in the area where the patient recovers (Table 50.7). Postoperatively, nasal
CPAP can be helpful if nasal packing is not needed. The use of nasal CPAP in the
immediate postoperative period may help to reduce upper airway edema, but it is very
irritating and drying and its use should be individualized.

TABLE 50.7. EMERGENCIES SURGICAL
TREATMENT OF SLEEP APNEA



Nasal Surgery
The relationship between nasal obstruction and sleep-disordered breathing remains
unclear. As a general principle, increased nasal resistance is known to increase the
collapsibility of the pharynx. Normal patients can develop significant sleep disordered
breathing by occluding their noses with petrolatum-coated cotton balls. In addition,
several studies noted that nasal packing is associated with hypoxemia. Deaths have been
reported in patients who have had nasal packing. A common theme in these publications
is that there is also considerable variability in the response to nasal occlusion. Thus, it
appears that induced nasal obstruction is associated with sleep fragmentation, sleep
deprivation, increased respiratory effort, and obstructive hypopneas and apnea in certain
patients (Table 50.8).

TABLE 50.8. COMPLICATIONS SURGICAL
PROCEDURES FOR SLEEP APNEA



Palatal Surgery
Three types of palatal surgery are performed for OSAS: UPPP, uvulopalatoplasty, and
transpalatal advancement pharyngoplasty. UPPP is the most commonly performed
surgical pro-cedure for OSAS. The ideal UPPP candidate has isolated retropalatal
collapse, and patients with less severe apnea respond more favorably to UPPP than
patients with severe apnea.
Contraindications to performing UPPP include velopharyngeal insufficiency, a
submucous cleft palate, and patients who have special voice or swallowing
considerations. The complications associated with UPPP include bleeding,
velopharyngeal insufficiency, voice change, pharyngeal foreign body sensation,
nasopharyngeal stenosis, respiratory distress, and death. Finally, because UPPP is
performed in the operating room and patients require hospitalization, the cost is
significantly higher than uvulopalatoplasty procedures. Although UPPP has a similar
efficacy rate, costs significantly more, and is associated with more significant
complications than uvulopalatoplasty procedures, UPPP is still preferable or necessary in
many patients. Uvulopalatoplasty procedures can be performed only in patients who have
nearly normal oxygen levels documented by polysomnography. Thus, many patients are
excluded from uvulopalatoplasty outpatient procedures on this basis. Also, patients with
marked tonsillar hypertrophy or prominent posterior pharyngeal wall vertical rugae
should undergo UPPP. Finally, patients with a strong gag reflex usually require UPPP.
Uvulopalatoplasty is an outpatient procedure that is performed most commonly with a
laser (LAUP). Other methods include use of electrocautery, snare (10), or cold-knife.
LAUP usually requires multiple sessions, whereas other uvulopalatoplasty procedures
can be performed in a single stage. Uvulopalatoplasty addresses only redundant tissue of
the soft palate and uvula, whereas UPPP addresses these structures as well as the lateral
pharyngeal walls and tonsils. Initially, uvulopalatoplasty was introduced for the treatment
of snoring and now is beginning to be used in patients who have OSAS. Mickelson (14)
reported on 13 LAUP-treated OSAS patients; the response rate was 53.8%. Walker et al.
evaluated 38 LAUP-treated OSAS patients and reported a 47.4% response rate. A
response was defined as a greater than 50% reduction in the postoperative RDI in all
three studies. If the definition of a successful surgical outcome is an RDI of fewer than 20
events per hour, then in Walker's study, the response rate to LAUP was 65.8%. Most
patients who undergo LAUP have mild apnea; thus, their pretreatment RDI is often lower
than 20 events per hour, the same number used to define success. Using the strictest
criteria for success, postoperative RDI below 20 and a greater than 50% reduction in the
postoperative RDI, the response rate for LAUP-treated OSAS patients was 44.7% in
Walker's study (15). LAUP outcome data reported by Walker compared favorably with
the UPPP data (44.7% response rate for LAUP versus 40.7% response rate for UPPP). A
recent report indicates that the response to UPPP for OSA decreases progressively over
the years. It was also observed that UPPP in combination with tonsillectomy was more
effective than UPPP alone (16).
Patient evaluation and selection are critical for a successful outcome and safety in
patients undergoing LAUP. The LAUP Practice Parameters (9) suggest that all patients
have objective testing before treatment; a postoperative study is also necessary. LAUP
may be offered as an alternative to UPPP if polysomnography demonstrates an RDI of
fewer than 20 events per hour of sleep and if the lowest oxygen saturation did not go
below 85%. If the apnea is more severe and the patient prefers LAUP to UPPP treatment,
then the patient must be a regular nasal CPAP user with a recent polysomnographic
titration. LAUP is contraindicated in patients who have a hyperactive gag reflex,
mandibular retrognathia with relative macroglossia, velopharyngeal insufficiency, a
bleeding disorder, or a submucous cleft palate. Complications include minor bleeding,
oral candidiasis, and temporary velopharyngeal insufficiency. The bleeding rates are low
(1% to 3%), and no cases of permanent velopharyngeal insufficiency, nasopharyngeal
stenosis, airway compromise, or death have been reported to date (13).
A transpalatal advancement pharyngoplasty is a palatal advancement procedure that can
be performed after UPPP failure or in conjunction with UPPP. This approach combines a
conservative UPPP with advancement of the soft palate at the junction of the hard and
soft palates. The advancement is performed by removing a portion of the posterior hard
palate and suspending the soft palate anteriorly. These investigators reported on a total of
11 patients, six of whom had only a transpalatal advancement. The response rate, defined
as an RDI of fewer than 20 events per hour, is 67% in the patients who underwent only
this procedure. Complications included an oronasal fistula, flap necrosis, and wound
dehiscence. The investigators noted that patients who may need to go on to a bimaxillary
advancement should not undergo this procedure because of concerns about the blood
supply to the palate. The role of this procedure in the care of OSAS patients requires
further study.
Tongue-Base Reduction Procedures
A variety of procedures address obstruction at the level of the base of tongue (retrolingual
space): lingual tonsillectomy, laser midline glossectomy (LMG), lingualplasty, and
radiofrequency tissue ablation of the tongue base. A lingual tonsillectomy is usually
performed with a laser. In an LMG procedure, a CO
2
laser is used to extirpate a
rectangular strip of the posterior portion of the tongue. A lingualplasty is a modification
of the LMG procedure; the lingualplasty involves the additional excision of lateral tongue
tissue, which has been shown to have response rates superior to the LMG procedure
alone. Radiofrequency tissue ablation of the tongue base is a less invasive procedure that
can be used to reduce the size of the base of the tongue. This procedure can be performed
in the operating room and has been done in the office as well. A needle electrode is
placed into the tongue below the mucosa and energy is applied to multiple areas. Most
patients require multiple staged treatment sessions. The effectiveness of this procedure is
still being studied (17). Patients undergoing these procedures usually require a temporary
tracheotomy to support the airway in the postoperative period.
The outcome following LMG was evaluated in 12 patients, 11 of whom failed previous
UPPP. The response rate, defined as at least a 50% reduction in postoperative RDI, was
41.7%. In a second study, 22 patients underwent LMG with the lingualplasty
modifications, 14 of whom had UPPP failures; the remaining eight patients had a UPPP
performed in conjunction with the LMG procedure. The response rate in this series was
77%, with a response rate defined as an RDI of fewer than 20 events per hour and at least
a 50% reduction from the preoperative RDI. Complication rates are almost 25% and
include bleeding, taste change, odynophagia and dysphagia, and tongue edema. To date,
few physicians are trained to perform these procedures, and the complication rates are
significant, precluding widespread application at this time (18).
Maxillomandibular Procedures
The principle of maxillomandibular surgery in OSAS is to advance the skeletal support of
the soft tissues that collapse during sleep. The lack of success following UPPP is often
attributed to persistent obstruction at the level of the base of the tongue. To correct the
obstruction at multiple sites in the airway, Riley et al. explored the use of
maxillomandibular surgery in combination with UPPP and proposed a two-phase surgical
protocol to reconstruct the upper airway in patients with OSAS. Patients who completed
this surgical protocol had a 97% success rate, higher than the success achieved with nasal
CPAP. This landmark paper, published in 1992, demonstrated that the use of a logical
surgical protocol in the management of patients with OSAS resulted in long-term
success.
Maxillomandibular surgery consists of many different techniques to advance the skeletal
support of the tongue and pharynx. These procedures most commonly are performed after
other more conservative procedures have failed. In patients who have severe OSAS and
maxillomandibular deficiency, the maxillofacial surgery may be performed in
combination with soft tissue procedures as the initial treatment. Maxillomandibular
surgery includes mandibular advancement with genioglossus advancement, hyoid
myotomy and suspension, and maxillomandibular osteotomy and advancement (MMO).
The combined procedure of inferior sagittal mandibular osteotomy and genioglossal
advancement with hyoid my-otomy and suspension (GAHM) with or without UPPP was
classified as phase I surgery. If phase I fails, it is followed by phase II surgery 6 months
or longer after completing phase I. Phase II surgery consists of an MMO, also known as
bimaxillary advancement.
Mandibular Osteotomy with Genioglossus Advancement
A number of techniques have been described to advance the mandible. The goal of these
procedures is to enlarge and stabilize the retrolingual airway by advancing the insertion
of the genioglossus or geniohyoid muscles without moving the entire mandible or teeth.
Limited mandibular osteotomies with genioglossus advancement has proved efficacious
and is associated with minimal morbidity. This technique is performed by creating a
bicortical rectangular osteotomy in the mandible at the geniotubercle. This rectangular
piece of bone, which includes the geniotubercle, is advanced anteriorly and rotated 90
degrees. This procedure anteriorly advances the insertion of the genioglossus muscle 10
to 14 mm and increases the tension placed on the tongue. The anterior mandibular
osteotomy (AMO) is presently the preferred genioglossus advancement procedure.
Multiple other techniques were abandoned, mainly as a result of weakening of the
anterior mandible with mandibular fracture being a concern as well as unsightly cosmetic
changes due to protrusion of the chin.
Hyoid Myotomy and Suspension
Hyoid myotomy and suspension have been used in conjunction with mandibular
advancement techniques to enlarge the posterior airway space. This procedure advances
the hyoid bone anteriorly, which advances the epiglottis as well as the base of tongue.
Initially, this procedure was performed by suspending the hyoid upward and anterior to
the inferior aspect of the mandible. Various techniques were used to stabilize the hyoid
bone, such as permanent sutures, fascia lata, or stainless-steel wire. In 1992 a modified
technique in which the hyoid is suspended to the thyroid cartilage was adopted, and
results appear promising (19).
Riley et al. reported their results in 55 patients who underwent inferior sagittal
mandibular osteotomy and GAHM. Of these 55 patients, 49 had UPPP and GAHM, and
six were considered to have obstruction only at the retrolingual level and therefore
underwent GAHM alone. This study demonstrated that 65.3% of the patients responded
to surgical intervention. The definition of response was an RDI below 20, a 50% or more
reduction from the preoperative RDI, and minimal oxygen desaturation. Lack of response
to this procedure was thought to relate to the degree of obesity as well as the degree of
mandibular deficiency. Complications included one mandibular fracture associated with a
wound infection, transient anesthesia of the incisors, and two cases of permanent injury
to the incisors.
Maxillomandibular Osteotomy and Advancement
Maxillomandibular osteotomy and advancement (MMO), also referred to as bimaxillary
surgery, is an alternative to a permanent tracheostomy in patients who have otherwise
failed more conservative surgical alternatives. In general, patients who undergo this
procedure have severe OSAS, are morbidly obese, and are otherwise reasonably healthy
patients (19). The goal of this procedure is to advance the maxilla and mandible as far
anteriorly as possible. This procedure is limited by the ability to stabilize the segments
and the aesthetic facial changes associated with this procedure. This procedure is phase II
of the surgical protocol described by Riley et al. to correct OSAS.
In a series of 306 operations, 91 patients underwent MMO primarily after an unsuccessful
outcome following phase I treatment. The overall response rate was 97.8% for the MMO
procedure with a mean follow-up of 9 months; the mean RDI decreased from 68.3 to 8.4.
The lowest oxygen saturation increased, and the mean percentage of stage 3 and stage 4
sleep as well as REM sleep also increased. Other reports confirm that MMO, performed
after other surgical procedures have failed or in combination with UPPP, produces
excellent outcomes in patients with severe OSAS. Transient anesthesia of the face and
cardiac arrhythmias were reported as complications associated with this procedure.
Tracheotomy
A permanent tracheotomy most commonly is performed in a patient with severe OSAS
who cannot tolerate nasal CPAP and has failed other surgical procedures. A temporary
tracheotomy is performed to secure the airway in the postoperative period, usually until
the risk of a postoperative hemorrhage is no longer present and edema has resolved.
Temporary tracheotomies usually are performed using standard techniques, whereas
permanent tracheotomies often are performed with cervical skin flaps sutured to the
tracheal fenestration. Closure of this type of tracheotomy requires a surgical procedure. In
either case, a tracheotomy in an OSAS patient is quite challenging because these patients
often have significant cervical obesity, short necks, and a low-lying larynx and trachea.
Indications for a permanent tracheotomy usually include morbid obesity, significant
cardiac arrhythmias associated with apneic events, severe apnea with oxygen desaturation
below 40% to 50% documented on polysomnography, cor pulmonale, and disabling
somnolence. Certainly, nasal CPAP failure is a prerequisite in all patients for which this
procedure is recommended. Tracheotomy reduces the morbidity and mortality associated
with OSAS. Surgeons reviewed three series of patients who underwent a tracheotomy; a
total of 99 patients were reviewed. Most patients were noted to have almost complete or
complete relief of their disabling somnolence, cardiac arrhythmias, and cor pulmonale.
Hypertension improved or resolved in many of these patients, sleep architecture
improved or normalized, and many patients were able to return to work. Almost all
attempts at closure of the tracheostomy resulted in recurrence of the OSAS.
Complications included stomal granulation tissue, infections, and psychosocial problems
associated with a permanent tracheotomy. Recent advancements in the options of
tracheotomy cannulae for patients with permanent tracheotomies have allowed patients
more comfort and have decreased the high maintenance care required by patients with a
tracheotomy. A tracheotomy remains a life-saving procedure and is necessary in certain
patients who have severe apnea.

HIGHLIGHTS
Obstructive sleep apnea syndrome is a laboratory diagnosis of a
minimum number of obstructive apneas and hypopneas per
hour of sleep combined with clinically evident signs and
symptoms.
The prevalence of OSAS in American middle-aged adults is 4%
of men and 2% of women. The prevalence is higher in the
elderly population. In the United States, current projections of
the prevlence of OSAS range from 7 to 18 million people.
Obstructive sleep apnea syndrome is associated with the
following diseases: (a) hypertension, (b) congestive heart
failure, (c) myocardial infarction, (d) cerebrovascular accidents,
(e) depression, and (f) injuries resulting from excessive daytime
sleepiness.
The definitive diagnosis of OSAS is made by nocturnal
polysomnography performed in a sleep laboratory. The role of
portable studies for the diagnosis of OSAS is rapidly evolving.
Obstructive sleep apnea syndrome is a disorder characterized
by recurrent collapse of the pharyngeal airway during sleep.
Most OSAS patients do not have a specific space-occupying
mass; more commonly, they have disproportionate anatomy.
Nonsurgical treatment options for OSAS include weight loss,
elimination of alcohol, oral and nasal appliances, positional
devices, and nasal CPAP.
Nasal CPAP is still considered the first-line therapy in OSAS.
Nasal CPAP corrects obstructive respiratory events and
improves morbidity associated with OSAS. Compliance with
treatment remains a serious problem in patients using nasal
CPAP.
The most commonly performed surgical procedure for OSAS is
the UPPP. Laser-assisted uvulopalatoplasty and other outpatient
palatal procedures are effective in the treatment of snoring and
in the treatment of OSAS in well-selected patients.
Awake fiberoptic intubation, judicious use of perioperative
narcotics, postoperative monitoring with pulse oximetry, and
postoperative use of steroids or nasal CPAP have all
contributed to the improved perioperative management of the
patient with OSAS.
Following a surgical procedure in a patient with OSAS, a
follow-up polysomnogram is necessary to assess outcome.

This chapter is dedicated to the author's mother, Geraldine Paloyan.
CHAPTER REFERENCES
1. Walker RP, Gatti WM, Poirier N, et al. Objective assessment of snoring before and after laser-
assisted uvulopalatoplasty. Laryngoscope 1996;106:13721377.
2. Armstrong MW, Wallace CL, Marais J. The effect of surgery upon the quality of life in snoring
patients and their partners: a between-subjects case-controlled trial. Clin Otolaryngol Allied Sci
1999;24:510522.
3. Loth S, Petruson B, Wiren L, et al. Better quality of life when nasal breathing of snoring men is
improved at night. Arch Otolaryngol Head Neck Surg 1999;125:6467.
4. Carskadon MA, Dement WC. Normal human sleep: an overview. In: Kryer MH, Roth T, Dement
WC, eds. Principles and practice of sleep medicine. Philadelphia: WB Saunders, 1994:1625.
5. Woodson BT, Garancis JC, Toohill RJ. Histopathologic changes in snoring and obstructive sleep
apnea syndrome. Laryngoscope 1991;101:13181322.
6. Friedman M, Tanyeri H, La Rosa M, et al. Clinical predictors of obstructive sleep apnea.
Laryngoscope 1999;109:19011907.
7. Vaidya AM, Petruzzelli GJ, Walker RP, et al. Identifying obstructive sleep apnea in patients
presenting for laser-assisted uvulopalatoplasty. Laryngoscope 1996;106:431437.
8. Gyulay S, Olson LG, Hensley MJ, et al. A comparison of clinical assessment and home oximetry
in the diagnosis of obstructive sleep apnea. Am Rev Respir Dis 1993;147:5053.
9. Standards of Practice Committee of the American Sleep Disorders Association. Practice
parameters for the use of laser-assisted uvulopalatoplasty. Sleep 1994;17:744748.
10. Weingarten C. Snare uvulopalatoplasty. Laryngoscope 1995;105:10331036.
11. Levin BC, Becker GD. Uvulopalatopharyngoplasty for snoring: long-term results. Laryngoscope
1994;104:11501152.
12. Walker RP, Garrity T, Gopalsami C. Early polysomnographic findings and long-term subjective
results in sleep apnea patients treated with laser-assisted uvulopalatoplasty. Laryngoscope
1999;109:14381441.
13. Walker RP, Gopalsami C. Laser-assisted uvulopalatoplasty: postoperative complications.
Laryngoscope 1996;106:834838.
14. Mickelson SA. Laser-assisted uvulopalatoplasty for obstructive sleep apnea. Laryngoscope
1996;106:1013.
15. Walker RP, Grigg-Damberger MM, Gopalsami C. Uvulopal-atopharyngoplasty versus laser-
assisted uvulopalatoplasty for the treatment of obstructive sleep apnea. Laryngoscope
1997;107:7682.
16. Boot H, van Wegen R, Poublon ML, et al. Long-term results of uvulopalatopharyngoplasty for
obstructive sleep apnea syndrome. Laryngoscope 2000;110:469475.
17. Powell NB, Riley RW, Guilleminault C. Radiofrequency tongue base reduction in sleep-
disordered breathing: a pilot study. Otolaryngol Head Neck Surg 1999;120:656664.
18. Chabolle F, Wagner I, Blumen MB, et al. Tongue base reduction with hyoepiglottoplasty: a
treatment for severe obstructive sleep apnea. Laryngoscope 1999;109:12731280.
19. Li KK, Riley RW, Powell NB, et al. Postoperative airway findings after maxillomandibular
advancement for obstructive sleep apnea syndrome. Laryngoscope 2000;110:325327.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

51 LARYNGITIS
Head & Neck SurgeryOtolaryngology
51




LARYNGITIS
GREGORY N. POSTMA
MILAN R. AMIN
JAMES A. KOUFMAN

G.N. Postma and J.A. Koufman: Center for Voice Disorders, Department of Otolaryngology, Wake
Forest University School of Medicine, Winston-Salem, North Carolina.
M.R. Amin: Center for Voice and Swallowing, Hahnemann University Hospital, Philadelphia,
Pennsylvania.


Childhood Laryngitis
Viral Laryngitis
Acute Laryngotracheitis (Croup)
Secondary Bacterial Laryngitis
Acute Supraglottitis
Laryngeal Diphtheria
Laryngopharyngeal Reflux
Spasmodic Croup
Adult Laryngitis
Viral Laryngitis
Bacterial Laryngitis
Noninfectious Laryngitis in Adults
Laryngopharyngeal Reflux
Traumatic Laryngitis
Thermal Injury
Angioedema
Allergic Laryngitis
Relapsing Polychondritis
Systemic Lupus Erythematosus
Epidermolysis Bullosa and Cicatricial Pemphigoid
Amyloidosis
Chronic Granulomatous Laryngitis
Tuberculosis
Syphilis
Leprosy
Histoplasmosis
Blastomycosis
Scleroma
Sarcoidosis
Wegener Granulomatosis
Immunocompromised Host
Radiation Laryngitis
Chapter References
Laryngitis, frequently misused as a synonym for hoarseness, refers to any acute or
chronic, infectious or noninfectious, localized or systemic inflammatory process
involving the larynx. The clinical presentation of laryngitis depends on its cause, the
amount of tissue edema, the region of the larynx primarily involved, and the patient's age.
Patients with laryngitis may present with one or more symptoms: dysphonia,
odynophonia, dysphagia, odynophagia, cough, dyspnea, or stridor. The diagnosis is based
on the history and the laryngeal examination, but it sometimes requires special diagnostic
tests, such as cultures, blood tests, skin tests, pH monitoring, or radiographs (Table 51.1).

TABLE 51.1. DIAGNOSIS LARYNGITIS



CHILDHOOD LARYNGITIS
The smaller pediatric airway is much more susceptible than the adult airway to
obstruction from edema. Equivalent amounts of mucosal edema produce critical
narrowing in children but cause minimal or no symptoms in adults. Laryngitis is therefore
more often a life-threatening illness requiring airway management in infants and children.
Viral Laryngitis
The most common cause of laryngitis is viral infection. This type of nonobstructive
laryngitis is clinically mild and often is associated with an upper respiratory infection
(URI). Patients may present with low-grade fever, mild dysphonia, cough, or rhinitis.
Rhinovirus, parainfluenza, respiratory syncytial virus (RSV), and adenovirus have been
implicated. Other viral illnesses causing laryngitis include influenza, measles, mumps,
pertussis, and chickenpox.
The diagnosis is based on the history and symptoms, and examination of the larynx does
not always need to be performed. When examined, the laryngeal mucosa is erythematous
and edematous, with normal vocal fold mobility. Common viral laryngitis is usually self-
limited, and treatment is aimed at hydration and humidification, but antipyretics and
decongestants also are prescribed frequently.
Acute Laryngotracheitis (Croup)
Acute laryngotracheitis (croup) is a common viral infection that generally affects children
under 5 years of age (1). Typically, this illness lasts 3 to 7 days and is common in the
autumn and winter.
Parainfluenza I is the most commonly implicated virus, but parainfluenza II, influenza A,
rhinovirus, and RSV also may be causative. The child first develops a febrile URI,
followed days later by the classic barky or croupy cough; the cough is usually
nonproductive and worsens at night. Diagnosis is based on the history and on lateral neck
radiographs, which usually reveal the classic steeple sign, caused by subglottic
narrowing due to edema.
Usually, croup is self-limited, but if significant edema develops, airway difficulty may
ensue. Stridor with intercostal and supraclavicular retractions becomes prominent as the
child struggles for air. In severe cases, airway edema may progress, exhaustion may
ensue, and complete airway obstruction may occur.
In laryngotracheitis, the subglottic larynx is the primary site of inflammation and edema
formation, although the trachea also may be involved. In severe cases, epithelial
sloughing associated with tenacious mucoid secretions may accompany the inflammation
and further compromise the airway. It should be noted that the supraglottic larynx is
usually unaffected in laryngotracheitis; this helps to differentiate it from other causes of
airway obstruction.
Treatment is directed at reducing the edema, thinning the secretions, and, in severe cases,
establishing an airway. Humidification and hydration help thin the secretions and soften
the crusts in the airway. Aerosolized epinephrine and high-dose corticosteroids are often
used to prevent further progression of the edema (2,3 and 4). If impending airway
obstruction develops, in-tubation or tracheotomy is required to secure the airway and
permit adequate pulmonary toilet. Antibiotics are indicated for secondary bacterial
infection, which may be caused by staphylococci or pneumococci.
Secondary Bacterial Laryngitis
Some patients with laryngotracheitis progress to develop secondary bacterial infection of
the airway. These patients present with various degrees of airway obstruction, stridor,
tachypnea, tachycardia, cough, fever, and drooling. This condition is more serious and
usually is attended by high fever and purulent drainage. This condition has the potential
to obstruct the airway and requires prompt diagnosis and treatment (5).
The organisms usually responsible are Haemophilus influenzae, pneumococcus, and
hemolytic streptococci. Antibiotic therapy should be directed at these organisms. When
possible, culture and Gram stain of the exudate should be obtained. Airway support is
often needed in these patients.
Acute Supraglottitis
Acute supraglottitis, also called epiglottitis, is a life-threatening infection, most often
caused by H. influenzae type B (6,7). Children 2 to 4 years of age are most often affected,
and most cases of supraglottitis occur in the winter and spring. This condition is an
emergency because airway obstruction and death can develop rapidly.
Typically, the illness progresses rapidly over 2 to 6 hours, with the onset of fever, sore
throat, and inspiratory stridor. The child's voice tends to be muffled, but a croupy cough
is unusual. As the supraglottis becomes increasingly edematous, airway obstruction may
develop. Affected children are frightened and ill appearing, often stridulous and sitting
upright in the sniffing position. They often drool because swallowing is painful.
A presumptive diagnosis of supraglottitis is based on the history and clinical findings, but
because laryngeal examination in the emergency department may precipitate airway
obstruction, it is not recommended. Additionally, drawing blood, starting intravenous
lines, and other necessary procedures are performed after the airway is established.
Lateral soft tissue radiographs typically reveal the classic thumb sign of the edematous
epiglottis. In addition, the entire supraglottis may be hazy and indistinct with a dilated
hypopharynx (6). When airway obstruction is severe, treatment should not be delayed to
obtain radiographs. If radiographs are deemed necessary, the child should be attended
constantly by personnel capable of immediate intubation if airway obstruction occurs.
Children with suspected supraglottitis should be taken to the operating room immediately
to establish the diagnosis and control the airway. Instruments necessary for rigid
bronchoscopy and tracheotomy must be ready in case the airway is lost before intubation.
At the time of direct laryngoscopy, the epiglot-tis usually appears very swollen and
cherry red, as do the aryepiglottic folds and false vocal cords. The true vocal folds and
subglottis usually appear normal.
After diagnosis, the patient should be orally intubated. The oral endotracheal tube then
can be converted to a nasotracheal tube or a tracheotomy may be performed. In some
settings, such as institutions without skilled pediatric intensive care staff available around
the clock, tracheotomy may be preferred to endotracheal intubation because it is easier to
secure and maintain in the small patient with a tenuous airway.
Antimicrobial therapy is initiated against H. influenzae. Extubation is usually possible
after 48 to 72 hours, at which time the edema has subsided sufficiently to allow an air
leak around the endotracheal tube. Direct laryngoscopy is the most reliable technique to
ensure resolution of the inflammation before extubation.
H. influenzae type B polysaccharide vaccine has been available since 1985 for children
over 18 months of age. Since 1988, conjugate vaccines have made possible the
immunization of children beginning at 2 months of age. Immunization has resulted in a
dramatic decrease in the incidence of supraglottitis (7). Although H. influenzae remains
the leading cause of supraglottitis, -hemolytic streptococci and staphylococcus also may
cause supraglottitis.
Unfortunately, the mortality rate for supraglottitis today remains significant despite
advances in airway management because the diagnosis may be missed in the early stages
of the illness, with rapid progression to airway obstruction. Differentiating acute
supraglottitis from laryngotracheitis is not always easy, but this differentiation is
essential.
Laryngeal Diphtheria
Laryngeal diphtheria is uncommon; however, outbreaks of diphtheria have been reported
in Eastern Europe, probably due to low immunization rates (8). This disease is caused by
Corynebacterium diphtheriae and generally affects people over 6 years of age. A febrile
illness of slow onset associated with sore throat and dysphonia is followed by progressive
airway obstruction.
The organism causes an exudative inflammatory response of the mucous membranes,
which results in a thick, gray-green, plaquelike membranous exudate over the tonsils,
pharynx, and larynx. Characteristically, the exudate is difficult to dislodge and bleeds
when removed. Cultures and smears are obtained for confirmation of the diagnosis.
Treatment consists of establishing a safe airway, administration of diphtheria antitoxin,
and erythromycin or penicillin to eradicate the organism. Intubation is contraindicated
because it may dislodge a plaque and cause airway obstruction; thus, tracheotomy often is
performed. If the patient has been previously immunized against diphtheria, the disease
still may occur but tends to be mild.
Laryngopharyngeal Reflux
Laryngopharyngeal reflux (LPR), the reflux of gastric contents into the laryngopharynx,
is ubiquitous in children, yet the diagnosis may be difficult to make. Laryngopharyngeal
reflux is associated with laryngomalacia, vocal nodules, polyps, granulomas, laryngeal
and tracheal stenosis, and laryngospasm. Laryngopharyngeal reflux also may play a
causal role in asthma, sudden infant death syndrome, and aspiration pneumonia (9,10).
A high index of suspicion is necessary for LPR to be considered in cases of laryngitis;
unfortunately, the only reasonably sensitive test for this condition is ambulatory 24-hour
double-probe pH monitoring (9). Other tests, such as barium esophagography,
radionuclide scanning, and the lipid-laden mac-rophage test, lack diagnostic sensitivity to
be of value in most cases.
Spasmodic Croup
Spasmodic or false croup is a noninfectious form of laryngeal inflammation, possibly
related to allergy or LPR. It generally affects children 1 to 3 years of age. Occasionally it
is associated with a URI but not with a significant fever. The child usually wakes at night
with a barky cough, stridor, and mild dyspnea. The coughing paroxysms may be followed
by vomiting, which may terminate the attack. These episodes may occur as an isolated
event or recur over 2 to 3 nights. The child is usually asymptomatic during the day.
Examination shows mildly erythematous laryngeal mucosa, with subglottic edema.
Humidification is usually all that is required to alleviate the symptoms. Spasmodic croup
may be confused with laryngotracheitis and with laryngospasm.
ADULT LARYNGITIS
Laryngitis in adults is usually less serious than in children because the larger adult larynx
can accommodate swelling without obstructing as readily. Most commonly, adult
laryngitis is caused by a viral URI, smoking, or LPR. Unlike children, adults can have
chronic laryngitis that may go unrecognized for many years.
Viral Laryngitis
Infectious laryngitis in adults is most commonly associated with a viral URI. Patients
present with a generalized viral syndrome and dysphonia that is characterized by voice
breaks, episodic aphonia, hoarse cough, and a lowering of the vocal pitch. Rhinoviruses
are the most common causative agents.
Characteristically, the vocal fold mucosa is erythematous and edematous. The disease is
self-limited and is treated with humidification, voice rest, hydration, smoking cessation,
cough suppressants, and expectorants. Antibiotics are indicated only for secondary
bacterial infection.
Bacterial Laryngitis
Supraglottitis is manifested by fever, sore throat, a muffled voice, odynophagia, and
dyspnea. The diagnosis is made by observing the swollen, red supraglottic structures by
fiberoptic laryngoscopy or by detecting the swollen supraglottis on a lateral neck
radiograph.
Haemophilus influenzae is the most common organism, but Streptococcus pneumoniae,
Staphylococcus aureus, and -hemolytic streptococci also are found. Close observation
with serial fiberoptic examinations is appropriate, with intubation or tracheotomy
reserved for progressive airway obstruction. Patients whose symptoms progress rapidly
over less than 24 hours are at high risk for airway compromise (11,12). Treatment
includes humidification, hydration, corticosteroids, and intravenous antibiotics.
Epiglottic abscess is an uncommon complication of bacterial laryngitis, and it occurs
more commonly in adults than in children. Tracheotomy followed by drainage is the
treatment of choice.
NONINFECTIOUS LARYNGITIS IN ADULTS
Laryngopharyngeal Reflux
Of all the causes of noninfectious laryngitis in adults, LPR is probably the most common.
It has been estimated that reflux affects 50 million Americans and that as many as 50% of
patients with laryngeal complaints have reflux-related causes (13,14).
Laryngopharyngeal reflux may be associated with an acute, chronic, or intermittent
pattern of laryngitis. Laryngopharyngeal reflux has been implicated in the development
of granulomas, stenosis, recurrent laryngospasm, globus pharyngeus, cervical dysphagia,
asthma, laryngeal carcinoma, and chronic cough (15,16). The highest reported association
(92%) is with subglottic stenosis (13).
Gastroenterologists consider reflux patients who deny gastrointestinal symptoms to be
atypical refluxers, but they are quite typical of the patients encountered in an
otolaryngology practice. Laryngopharyngeal reflux is underdiagnosed and un-dertreated
because the signs, symptoms, and mechanisms of LPR are quite different from those seen
in gastroenterology patients, who characteristically have heartburn, regurgitation, and
esophagitis. When compared with esophagitis patients, LPR patients have upright reflux,
normal esophageal acid clearance, and normal esophagography. Consequently, LPR
patients usually present with symptoms of dysphonia, cough, and frequent throat clearing
but often deny having heartburn (Table 51.2).

TABLE 51.2. COMPARISON OF
OTOLARYNGOLOGY PATIENTS WITH
LARYNGOPHARYNGEAL REFLUX (LPR) AND
GASTROENTEROLOGY PATIENTS WITH
GASTROESOPHAGEAL REFLUX (GER)



Examination of the larynx may reveal a variety of findings. Posterior laryngitis
demonstrating red arytenoids with interarytenoid mucosal hypertrophy is commonly seen
with LPR. Subglottic edema forming a pseudosulcus vocalis also is seen frequently.
The larynx may show diffuse edema, Reinke edema, or mucosal thickening without
significant erythema, which may cause ventricular effacement. Diffuse erythema with
granular, friable mucosa, and vocal process granulomas, with or without associated
laryngeal edema and erythema, also are seen. Although granulomas of the vocal process
may be caused by vocal abuse and endotracheal intubation, available data indicate that
LPR plays a role in many cases.
Ambulatory 24-hour double-probe pH monitoring is the current gold standard for the
diagnosis of LPR. (The second probe is placed in the hypopharynx, behind the laryngeal
inlet.) This technique is highly sensitive and specific for LPR and also delineates each
patient's reflux pattern, allowing individualized treatment (17).
Treatment of LPR includes dietary and life-style modifications and antireflux medication,
such as a histamine (H
2
) blocker or proton pump inhibitor (PPI). PPIs are the most
effective antireflux medicine available because, unlike the H
2
blockers, they can achieve
total suppression of gastric acid production. With H
2
blockers, treatment fails in about a
third of LPR patients, although these medicines are considerably less effective in severe
disease (13). Failures on PPIs occur less commonly and are often due to inadequate
dosing. Often, dosing is adjusted by performing ambulatory pH monitoring while the
patient is on medication (so-called drug efficacy tests). Patients who fail medical
antireflux therapy may require fundoplication.
Traumatic Laryngitis
Traumatic laryngitis is commonly caused by vocal abuse, but can also result from
persistent coughing, muscle tension dysphonia, or direct endolaryngeal injury. Such
patients present with various degrees of dysphonia and odynophonia. The mucosa of the
true vocal folds is hyperemic from dilated vessels on the vocal fold surface. Edema
within the Reinke space develops, and submucosal hemorrhage may occur. This form of
laryngitis is self-limited and subsides within a few days when treated with voice
conservation and humidification.
Thermal Injury
Laryngitis due to thermal damage to the larynx is well recognized. Patients complain of
dysphonia, odynophagia, and odynophonia. Exposure of the larynx to steam, smoke, or
very hot liquids or food (particularly if microwaved) leads to supraglottic edema and
erythema. It is more common in children. Laryngeal edema due to exposure to free-base
cocaine also may present a diagnostic dilemma. Treatment of such injuries is with
humidification, corticosteroids, and airway observation or intubation if the larynx is
severely edematous.
Angioedema
Acquired angioedema is an inflammatory reaction characterized by vascular dilation and
increased vascular permeability (18,19). It can be caused by a variety of substances and is
potentially life threatening if the larynx is involved. Etiologic agents include certain
medications [particularly angiotensin-converting enzyme (ACE) inhibitors], foods, insect
bites, transfusions, and infections.
Hereditary angioedema is an autosomally dominant deficiency of C1 esterase inhibitor
that leads to recurrent attacks of mucocutaneous edema. Diagnosis is based primarily on
the history, although the offending agent may not be readily apparent. Patients present
with rapid-onset edema that may involve the face, oral cavity, oropharynx, or larynx.
Treatment must be aggressive. Supplemental oxygen, epinephrine, corticosteroids,
antihistamines, and aminophylline are the mainstays of therapy; however, ACE inhibitor
related angioedema is not believed to be immunoglobulin E mediated, and such patients
therefore may be refractory to this therapy. If airway obstruction develops, intubation or
tracheotomy may be required. Chronic pretreatment of hereditary angioedema with
danazol appears to elevate levels of functional C1 esterase inhibitor and may help to
prevent recurrent episodes.
Allergic Laryngitis
Allergy-mediated inflammation involving the larynx is controversial. It may be
responsible for symptoms of chronic and recurrent dysphonia in some patients (20,21).
Evaluation for allergic laryngitis begins with a careful history, noting specific or chronic
environmental exposures, or association of symptoms with certain foods.
Examination may reveal laryngeal edema and polypoid mucosa as well as muscular
tension dysphonia. Associated findings of allergic shiners, a supratip nasal crease,
boggy nasal mucosa, or nasal polyps also may suggest an atopic etiology. The most
common triggering substances are insecticides, phenol, petroleum-based compounds, and
a variety of common environmental allergens. Diagnostic testing may include a standard
allergy evaluation (skin or RAST testing), and challenge testing with the suspected
triggering agent. Caution must be exercised with the latter, because there is a risk of
anaphylaxis with such methods. More common causes of laryngitis, such as LPR, should
be ruled out prior to proceeding to a diagnosis of primary allergic laryngitis.
Treatment primarily involves the avoidance of the inciting agent and the judicious use of
antihistamines, steroids, and immunotherapy. Adjunctive treatment measures may
include optimizing vocal hygiene with hydration and speech therapy to avoid pathologic
compensatory behaviors.
Relapsing Polychondritis
Relapsing polychondritis is characterized by episodes of inflammation and fibrosis with
destruction of the cartilage of the ears, nose, larynx, and tracheobronchial tree. Laryngeal
disease occurs in more than half the cases and is manifested by dysphonia, dysphagia,
and throat pain. Airway involvement leads to the high mortality seen with this disease.
Treatment includes dapsone, corticosteroids, and other immunosuppressive drugs.
Tracheotomy may be necessary.
Systemic Lupus Erythematosus
Systemic lupus erythematosus may produce laryngeal inflammation in up to a third of
patients. Symptoms range from intermittent dysphonia to airway obstruction, but
dysphonia and dyspnea are the most common symptoms. Examination may reveal edema
(particularly of the supraglottis), ulceration, or even vocal fold paralysis. Most patients
readily respond to systemic corticosteroid therapy (22).
Epidermolysis Bullosa and Cicatricial Pemphigoid
Epidermolysis bullosa and cicatricial pemphigoid represent autoimmune disorders
manifested by mucosal blister formation (23,24). Bullae or ulcerations heal by scar tissue
formation. Involvement of the larynx is relatively uncommon, but may result in
dysphonia and airway obstruction. Laryngeal findings include edema, raw mucosa,
bullae, ulcers, webs, and areas of stenosis in the larynx and trachea. Intubation should be
avoided if possible because the larynx appears to be particularly sensitive to trauma.
Patients may require a tracheotomy despite cortico-steroid and immunosuppressive
therapy. Stenosis may be treated by usual endoscopic techniques, once the primary
disease is under control.
Amyloidosis
Amyloidosis may involve the larynx alone or may be a component of systemic
amyloidosis (25). Laryngeal amyloidosis occurs as diffuse mucosal thickening,
submucosal nodules, or less commonly as polypoid lesions. Disease usually involves the
supraglottis. Patients are usually asymptomatic until the deposits involve the vocal folds
causing dysphonia or critically narrow the airway. Biopsy reveals an amorphous Congo
redstaining material. Symptomatic cases are treated by endoscopic removal of lesions.
Systemic disease is evaluated with appropriate immunoelectrophoretic studies. Life-long
follow-up is important with this condition because of its chronic nature.
CHRONIC GRANULOMATOUS LARYNGITIS
Chronic granulomatous diseases involving the larynx may be caused by a variety of
uncommon organisms and disease processes, some of which may mimic laryngeal
carcinoma. When granulomatous diseases are suspected, the clinician should elicit the
patient's past medical and travel history carefully.
Tuberculosis
Tuberculous laryngitis is the most common granulomatous disease of the larynx and
usually is associated with active pulmonary tuberculosis. Today, tuberculosis is seen
more frequently as a result of the human immunodeficiency virus epidemic and increased
immigration from endemic areas (26). Patients present with symptoms of dysphonia,
odynophagia, dyspnea, and odynophonia. Respiratory obstruction may develop in the
advanced stages of the disease. Systemic complaints of fever, night sweats, and weight
loss are common.
Laryngeal examination may reveal diffusely edematous and hyperemic mucosa involving
the posterior third of the larynx or granular exophytic lesions, which may resemble
carcinoma. The diagnosis is made by demonstrating the organisms by smear and culture.
Cultures are critical in guiding therapy because of increasing rates of mycobacterial drug
resistance (27). If tuberculous laryngitis is left untreated, stenosis may develop,
necessitating tracheotomy.
Syphilis
The larynx may become involved during the later stages of syphilis. Diffuse
erythematous papules, edema, and ulcers that mimic carcinoma along with cervical
lymphadenopathy are seen during the secondary stage. These may clear spontaneously
within several weeks. Gumma formation during the tertiary stage leads to fibrosis,
chondritis, and stenosis. Serologic tests for syphilis are diagnostic. Penicillin is the
treatment of choice.
Leprosy
Laryngitis caused by Mycobacterium leprae is rare in the United States. It most
commonly involves the supraglottic larynx, and the patient presents with a muffled voice,
odynophagia, and cough. Laryngoscopy reveals a nodular, edematous supraglottis with
ulceration. Diagnosis is made by biopsy, which reveals a chronic inflammatory cell
infiltrate with foamy cells that contain the M. leprae bacillus (28). Nasal smears for the
intracellular organisms may be diagnostic. Long-term combination treatment with
rifampin and dapsone is indicated. Tracheotomy may be required if stenosis develops.
Histoplasmosis
Histoplasmosis is a systemic mycotic disease caused by Histoplasma capsulatum, and it
may involve the larynx with nodular superficial granulomas that can ulcerate and become
painful. Histologic examination reveals granulation tissue composed of plasma cells,
macrophages containing the organisms, and giant cells, which may be confused with
carcinoma or tuberculosis. Diagnosis is made by the complement fixation test and by
culturing the organism.
Amphotericin B is the treatment of choice. Laryngeal stenosis may develop if extensive
ulceration leads to chondritis. In this instance, laser excision or tracheotomy may be
required to provide an adequate airway.
Blastomycosis
North American blastomycosis is a chronic pulmonary infection common in the
southeastern United States and is caused by the fungus Blastomyces dermatitidis. Patients
typically present with multiorgan involvement and, when the larynx is involved, with
severe dysphonia and cough.
The organism produces small, red, granular lesions of the laryngeal mucosa, which may
progress to painful abscesses and ulcerations. On histologic examination, caseous
necrosis with an acute inflammatory infiltrate, microabscesses, pseudoepitheliomatous
hyperplasia, and giant cells are seen. The periodic acid-Schiff (PAS)-positive yeast form
may be seen in the region of the microabscesses. Treatment is with long-term
amphotericin B, ketoconazole, or itraconazole. Without treatment, progressive fibrosis
with vocal cord fixation and pharyngocutaneous fistulas develop.
Scleroma
Scleroma is a chronic progressive infection caused by Klebsiella rhinoscleromatis. It
primarily involves the nasal cavity, but it may involve the laryngopharynx. The disease
has three overlapping clinical stages. The catarrhal stage is characterized by purulent
rhinorrhea, with nasal crusting and obstruction, followed by the granulomatous stage, in
which nodular granulomas form within the upper respiratory tract. The subglottis is most
commonly involved. The final, sclerotic stage is manifested as fibrosis and scar
formation. Dysphonia and respiratory obstruction may develop during the sclerotic stage,
but this usually takes many years.
The diagnosis is made by isolating the organism from the tissues or via
immunohistochemical studies. Histologically, foamy vacuolated histiocytes (Mikulicz
cells) and degenerated plasma cells (Russell bodies) are seen. Treatment is with
tetracycline, fluoroquinolones, or clofazimine. Endoscopic laser resection and
tracheotomy may be required.
Sarcoidosis
Sarcoidosis is a multisystem granulomatous disease of unknown etiology. The diagnosis
is based on finding noncaseating granulomas and pale diffuse edema of the supraglottis
and on excluding tuberculosis, Wegener granulomatosis, and fungal disease (29). Patients
present with dysphonia and various degrees of airway obstruction. Lesions usually
resolve with systemic and intralesional corticosteroids. Endoscopic surgery and trache-
otomy are rarely necessary.
Wegener Granulomatosis
Wegener granulomatosis is a systemic disease characterized by necrotizing granulomas
with vasculitis involving the respiratory tract and kidneys. Laryngeal involvement may
resemble acute laryngitis, but the eventual development of granulomatous ulcers
throughout the larynx provides the diagnosis. Subglottic involvement can lead to airway
obstruction, requiring tracheotomy and eventual laryngotracheoplasty. Diagnosis is based
on the histologic findings of necrotizing granulomas and vasculitis. The antinuclear
anticytoplasmic autoantibody test is highly specific for Wegener granulomatosis.
Treatment includes cyclophosphamide, corticosteroids, and optional trimethoprim-
sulfamethoxazole.
Immunocompromised Host
Patients with immune systems compromised by acquired immunodeficiency syndrome,
by immunosuppression for transplantation, or by chemotherapy or chronic corticosteroid
therapy are at risk for developing a variety of laryngeal opportunistic infections (Table
51.3) and malignancies, including Kaposi sarcoma, non-Hodgkin lymphoma, and
squamous cell carcinoma.

TABLE 51.3. LARYNGEAL OPPORTUNISTIC
INFECTIONS



Immunosuppressed patients may present with symptoms and physical findings consistent
with acute or chronic laryngitis. Opportunistic infections often mimic nonspecific
laryngitis and carcinoma (30). Failure to improve rapidly with empiric therapy should
lead to early direct laryngoscopy and biopsy. A high index of suspicion for laryngeal
opportunistic infections and malignancies must be maintained when caring for the
immunocompromised patient.
Radiation Laryngitis
Radiation therapy for laryngeal malignancies can result in a patient with dysphonia,
dysphagia, pain, or globus pharyngeus. Examination may reveal an erythematous,
swollen larynx with exudate and crusting. Treatment involves hydration, humidification,
and acid suppression, with steroids and antibiotics occasionally. The symptoms gradually
resolve following treatment. The differential diagnosis must include recurrent cancer,
LPR, radionecrosis, and hypothyroidism.

HIGHLIGHTS
Laryngitis is not a synonym for hoarseness but rather refers to
an inflammatory condition of the larynx.
Laryngitis is more serious in infants and small children because
the airway is smaller and more easily compromised by swelling
and edema.
Differentiation between severe laryngotracheitis and
supraglottitis must be made in the operating room with an
expert airway management team available to establish an
airway.
In adults, the most common causes of laryngitis are viral upper
respiratory infection and laryngopharyngeal reflux.
Laryngopharyngeal reflux may cause dysphonia, cough,
frequent throat clearing, or a globus sensation in children and
adults; however, patients with reflux laryngitis often deny
having heartburn or regurgitation.
Traumatic laryngitis is usually self-limited and is best managed
conservatively with voice rest, hydration, and humidification.
Angioedema involving the larynx requires aggressive treatment
aimed at suppressing the inflammatory response.
The incidence of laryngeal tuberculosis is increasing, and it
should be strongly considered in patients with laryngitis and
systemic symptoms, in immunosuppressed patients, or in
patients who immigrated from endemic areas.
The granulomatous disorders are diagnosed best by using
biopsy and special staining and culture techniques.
Immunocompromised patients with laryngitis must have close
follow-up. Failure of empiric treatment requires biopsy and
appropriate cultures.
Radiation laryngitis must be differentiated from recurrent
cancer, laryngopharyngeal reflux, radionecrosis, and
hypothyroidism.
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clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an
experimental investigation of the role of acid and pepsin in the development of laryngeal injury.
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laryngitis. Ann Otol Rhinol Laryngol 1995;104:550555.
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17. Koufman JA, Wiener GJ, Wu WC, et al. Reflux laryngitis and its sequelae: the diagnostic role of
ambulatory 24-hour pH monitoring. J Voice 1988;2:7889.
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disorder's presentation and treatment. Laryngoscope 1992;102:256260.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

52 HOARSENESS AND VOCAL CORD PARALYSIS
Head & Neck SurgeryOtolaryngology
52




HOARSENESS AND VOCAL CORD PARALYSIS
ROBERT C. WANG
ROBERT H. MILLER

R.C. Wang and R.H. Miller: Department of Surgery, University of Nevada School of Medicine, Las
Vegas, Nevada.


Anatomy
Vocal Cord and Cricoarytenoid Joint Motion
Voice Generation
Evaluation and Initial Assessment
Patient History
Physical Examination
Ancillary Tests
Vocal Cord Position and Synkinesis
Vocal Cord Paralysis in Children
Etiology
Management
Vocal Cord Paralysis in Adults
Evaluation and Diagnostic Tests
Management
Chapter References
Hoarseness is the perceived breathiness quality of the voice. There is increased airflow
required to produce the desired loudness of voice. Decreased maximal phonation
loudness and duration are often present. Dyspnea during phonation can occur. Aspiration,
particularly of thin liquids, may be an associated symptom. Hoarseness can be caused by
mucosal, submucosal, neuromuscular, cricoarytenoid joint, and functional abnormalities
of the larynx. Therefore, consideration should be given to the functional and anatomic
integrity of the larynx when evaluating for hoarseness.
ANATOMY
Hirano (1) reviewed the anatomy of the larynx in 1974 and demonstrated the vocal folds
to be multilayered. The outermost or mucosal layer consists of pseudostratified squamous
epithelium superior and inferior to the contact surface of the cord. The contact surface at
medial cord borders is covered with nonkeratinizing squamous epithelium.
The subepithelial tissues consist of a three-layered lamina propria overlying the vocalis
muscle, which is classified as a component of the thyroarytenoid muscle.
The superficial layer of the lamina propria, the Reinke space, contains a scant amount of
fibroblasts and elastic and collagenous fibers, and allows vibration of the overlying
mucosal cover layer over the underlying ligamentous and muscular base. The
intermediate layer is composed of mainly elastic fibers and a moderate number of
fibroblasts. It forms a portion of the vocal ligament. These fibroblasts are responsible for
much of the scar formation following surgical manipulation. The deep layer is made of
collagenous fibers and forms the remainder of the vocal ligament.
There are three groups of laryngeal musculature: adductors, abductors, and tensors. The
adductor group consists of the thyroarytenoid, lateral cricoarytenoid, and interarytenoid
muscles. The substantial thyroarytenoid muscle is the primary adductor of the larynx (2).
Innervation is supplied by the adductor branch of the recurrent laryngeal nerve. The
tensor group is composed primarily of the cricothyroid muscle, with contribution from
the thyroarytenoid muscle. The cricothyroid muscle is innervated by the external branch
of the superior laryngeal nerve. The sole abductor of the larynx is the posterior
cricoarytenoid muscle, innervated by the abductor branch of the recurrent laryngeal
nerve. The interarytenoid muscles receive bilateral innervation from the recurrent nerves.
Motor fibers of the vagus nerve originate in the nucleus ambiguus of the medulla,
coalesce to exit the jugular foramen, and then branch to supply specific muscle groups.
The superior laryngeal nerve branches from the main trunk of the vagus nerve near the
jugular foramen just below the nodose ganglion. Combined recurrent and superior
laryngeal nerve lesions usually indicate a lesion at the skull base or above.
VOCAL CORD AND CRICOARYTENOID JOINT MOTION
Vocal cord motion is produced primarily by the motion of the arytenoid cartilages
through their articulation with the cricoid cartilage facets within the diarthrodial
cricoarytenoid joints. Ligamentous and muscular attachments to the cricoarytenoid joints
act in concert to produce a hidden complex movement of the arytenoid (Fig. 52.1) (2).
This movement produces the motion of the membranous true vocal cords bounded by the
relatively stationary anterior commissure and the mobile vocal processes, which can be
examined in a patient. Is what appears to be a simple, linear two-dimensional medial-to-
lateral motion of the vocal processes in adductionabduction by routine examination
methods looking from above the larynx actually a much more complex movement when
analyzed in three dimensions? In experiments using cadaver larynges, it is apparent that
the movement of the arytenoid muscular process and arytenoid apex are quite complex,
and variable between larynges. It is important to realize that arytenoid motion can be
normally quite asymmetric from side to side (2). Therefore, differences in the degree of
vocal cord abduction is not necessarily an indication of disease, particularly if motion is
otherwise intact, and accurate adduction is present to provide good phonation and airway
protection.

FIGURE 52.1. Ligamentous attachments of the medial
cricoarytenoid joint. [Adapted from Wang RC. Three-
dimensional analysis of cri-coarytenoid joint motion.
Laryngoscope 1998;108(suppl):117; with permission.]



The end result of this complex motion yields vocal processes that meet accurately in the
midline, and translate laterally in a roughly two-dimensional linear fashion, much as one
sees with routine laryngeal examination, with a slight superior movement during
abduction (Fig. 52.2) (2). The vocalis ligament, cricoarytenoid ligament, and conus
elasticus are most important in controlling abduction, whereas the posterior
cricoarytenoid muscle and conus elasticus are crucial in limiting adduction. The vocalis
ligament prevents posterior displacement of the vocal process, whereas the cricoarytenoid
ligament and the posterior capsular ligament restricts anterior vocal process migration.
The anterior capsular ligament limits backward arytenoid cartilage tilting and lateral
movement of the arytenoid cartilage on the cricoid cartilage facet.

FIGURE 52.2. Three-dimensional arytenoid motion. A:
Top view. B: Front view. C: Side view. [Adapted from
Wang RC. Three-dimensional analysis of cricoarytenoid
joint motion. Laryngoscope 1998;108(suppl):117; with
permission.]



Additional motion is created by the visor effect of the cricothyroid joint, which is
controlled by the cricothyroid muscle. As the cricothyroid muscle contracts, it closes the
space between the anterior thyroid and cricoid cartilages, tensing the vocal cords and
adducting the cords by applying force to the medial anterior portion of the arytenoid,
similar to what the medial thyroarytenoid muscle does. Unilateral paralysis of the
cricothyroid muscle due to injury to the external branch of the superior laryngeal nerve
may create asymmetric vocal cord tension (greater on the normal side), inaccurate vocal
cord apposition (due to the cord on the side of paralysis being higher than the other), and
rotation of the anterior to posterior axis of the vocal cords (the posterior commissure
deviating to the side of paralysis) (3).
The posterior commissure is closed to prevent air escape during phonation and protect
against aspiration. It requires more than vocal process approximation by the
thyroarytenoid muscles to accomplish this. The medial surfaces of the arytenoid
cartilages between the vocal processes and the apex of the arytenoids appose together
tightly by the contracture of the interarytenoid muscles, which connect the arytenoids
along their posterior borders up to the apices. Posterior commissure defects causing
aspiration, air leakage, and hoarseness are commonly seen after prolonged indwelling
endotracheal tube injuries to the area. More significant injuries to the posterior
commissure, usually from endotracheal tube pressure, result in fibrosis of submucosal
tissues adjacent to and of the medial-posterior cricoarytenoid joint. This is termed
posterior glottic or commissure stenosis and can be manifested by medialized, immobile
cords with airway compromise. Laryngeal EMG and intraoperative palpation of the
arytenoids to assess passive mobility may be necessary to establish this diagnosis, and
distinguish it from bilateral vocal cord paralysis. Treatment is often difficult and unable
to restore full function. Prevention is accomplished by timely trache-ostomy in those
patients requiring long-term artificial ventilation. Diabetics may sustain posterior
commissure injuries sooner, and should be considered for earlier tracheostomy (4).
VOICE GENERATION
The larynx is a sound generator producing successive condensation and rarefaction of air
pressure. At the beginning of each phonatory cycle, the vocal cords are approximated,
allowing subglottic pressure to increase. This pressure progressively opens the glottis to
emit pulses of air producing condensation, alternating with rarefaction created by the
Bernoulli effect of airflow between the folds causing glottal closure, with a regular
periodicity (5). This process requires coordination between the laryngeal and chest
musculature. The folds vibrate at the fundamental frequency (lowest frequency, highest
amplitude) and multiple overtones at higher frequencies demonstrated on frequency-to-
amplitude plots using fast Fourier transformation. The folds vibrate in a horizontal plane,
and there is vertical undulation of the mucosa as the air passes through the glottis, seen as
waves on laryngeal stroboscopy. A change in the vibratory quality of the glottic mucosa
(e.g., decreased compliance), or inadequate apposition of the true vocal cords, interferes
with the generation of proper glottic mucosal waves, producing hoarseness.
EVALUATION AND INITIAL ASSESSMENT
Patient History
The patient with a change in voice may fear cancer of the larynx, although most lesions
causing hoarseness are due to benign changes of the mucosa or superficial submucosa.
The history should document alcohol and tobacco usage. Voice abuse, an antecedent or
ongoing respiratory tract infection, postnasal drainage from sinusitis, gastroesophageal
reflux, neurologic disorders, or a history of trauma or surgery may be elicited. It is
important to ascertain the duration and character of the voice change. A rough or breathy
voice indicates a glottic abnormality. A muffled or hot potato voice may be caused by
lesions of the oropharynx, hypopharynx, or tongue. A history of systemic and connective
tissue diseases should be investigated. Hypothyroidism results in laryngeal myxedema
and should be considered. Some medications (i.e., angiotensin-converting enzyme
inhibitors) have been implicated in chronic coughinduced voice changes. Patients with
chronic hoarseness with recalcitrance to medical treatment and a history of normal vocal
cord gross findings are found to have subtle abnormalities affecting vocal cord vibration,
functional disorders, or the initial stages of a neuromuscular disease such as spasmodic
dysphonia.
Physical Examination
Fiberoptic instrumentation has enhanced the ability of the otolaryngologist to view the
larynx. Before using these instruments, an attempt is made to examine the larynx with a
laryngeal mirror. A few patients, because of a hyperactive gag reflex or phobic response,
find it difficult to tolerate mirror examination.
It also may not be possible to see the glottis with a mirror in patients with a posteriorly
displaced epiglottis, or anteriorly situated glottis. In these cases, the rigid 70 or 90 degree
Hopkins rod-lens telescope may provide a more accurate and detailed inspection of the
larynx and hypopharynx. The major advantage of this technique is excellent resolution
(as with a mirror) and the ability to photodocument particular findings of the
examination. The disadvantage is that both the mirror and telescope examinations
interfere with normal speech and swallowing.
The flexible endoscope can easily be passed through the nasal passage of almost any
patient, and it is usually the best tolerated of all laryngeal examinations, especially in
children. It also provides a view of the nasal cavities, nasopharynx, oropharynx, and
hypopharynx, and allows prolonged dynamic visualization of laryngeal function, as may
be important in paradoxical vocal cord motion producing inspiratory stridor. Video or
single-frame photodocumentation is possible, although resolution is poorer than that with
telescopes.
Ancillary Tests
Videostroboscopy is an important adjunct in the workup of laryngeal disorders. Its value
resides in its ability to demonstrate subtle mucosal motion abnormalities, frequently when
gross pathology is not apparent during conventional laryngoscopic examination (6).
Electromyography (EMG) analyzes the electrical activity generated by muscle motor
units. In the past, muscle function in other parts of the body was studied by using this
technique, primarily by neurologists. Expertise in laryngeal anatomy is required to
evaluate phonatory musculature, and otolaryngologists often collaborate with
neurologists to perform laryngeal EMGs. Laryngeal EMG has become increasingly
useful in diagnosing the paralyzed larynx (7), and differentiating between vocal cord
fixation due to cricoarytenoid joint disorders ver-sus neuromuscular disease. Because the
thyroarytenoid and cricothyroid are easiest to access using an EMG needle, they are the
primary muscles studied. Information about recurrent and external branches of superior
laryngeal nerve function can be obtained by testing these two muscles. Evaluation of the
cricothyroid muscle can be accomplished by placing a needle electrode through the
overlying skin at the level of the cricoid cartilage. After the cartilage is encountered, the
needle is withdrawn slightly, and then it is directed superiorly and laterally, which places
the needle in the cricothyroid muscle. The thyroarytenoid muscle is examined by placing
the needle midline in the superior margin of the cricoid cartilage and then advancing it
superiorly and laterally to a position deep to the thyroid cartilage while still submucosal.
Phonation recruits diphasic or triphasic motor unit potentials in laryngeal muscles of 100
to 300 V amplitude, short duration (3 to 6 msec), and sharp-rising (< 200 V rise). Strap
muscles also may recruit with phonation but are generally of larger amplitude and longer
durations.
Evaluation of EMG tracings can reveal one of several patterns (Fig. 52.3). A loss of
muscle function (i.e., myopathy) produces a normal frequency of firing but a decrease in
the amplitude of the muscle action potential. A loss of nerve function demonstrates a
decrease in the frequency of firing but a normal amplitude if some fibers remain.
Fibrillation potentials, which are small with 0.5- to 2-msec durations, indicate loss of
neural innervation and are observed 3 weeks following an injury. Polyphasic potentials
are prolonged motor unit potentials, with four or more phases indicating that
reinnervation has begun. The timing and extent of functional recovery cannot be
determined by the presence of reinnervation potentials, due to syn-kinesis, which is
discussed below.

FIGURE 52.3. Laryngeal EMG patterns. A: Normal. B:
Fibrillation. C: Reinnervation.



Possible etiologies of hoarseness are shown in Table 52.1. The rest of the chapter focuses
on vocal cord paralysis.

TABLE 52.1. ETIOLOGY OF HOARSENESS



VOCAL CORD POSITION AND SYNKINESIS
The ultimate position of the vocal cord in laryngeal paralysis has long been attributed to
the activity of the cricothyroid muscle, which partially adducts the vocal cord by its
contraction. Thus, lesions involving both superior and recurrent laryngeal nerves are
expected to produce a lateral (also called intermediate or cadaveric) position, whereas
isolated recurrent nerve injuries would result in paramedian cord positions.
Unfortunately, no correlation is found between vocal cord position by transnasal
fiberoptic endoscopy, site of lesion, and cricothyroid and thyroarytenoid EMG
measurements (8).
Many immobile vocal cords (presumably due to paralysis and without cricoarytenoid
joint fixation) display muscle action potential activity by EMG. These vocal cords do not
undergo the expected atrophy of a denervated muscle. Twitching, spasms, and other
nonpurposeful movements may be appreciated, due to synkinetic reinnervation (9).
Antagonistic muscles are simultaneously stimulated, resulting in aberrant, or little to no
motion. Although hyperadduction in a paralyzed larynx has been reported to be treated
successfully with botulinum toxin injection to the thyroarytenoid and lateral
cricoarytenoid muscles (9), there are no reports of routinely producing abduction to
relieve airway obstruction due to bilateral vocal cord paralysis with paramedian
positioning. On the other hand, the sometimes adequate airways in children with
idiopathic bilateral cord paralysis can be explained by synkinesis with a balance favoring
more abduction. These patients are known to recover laryngeal motion after many years
of immobility. There appears to be a complex interplay between synkinetic reinnervation,
denervation, and forces exerted through connective tissue attachments of the larynx that
determines vocal cord position in the patient with a paralyzed, immobile larynx.
VOCAL CORD PARALYSIS IN CHILDREN
In children, differentiation should be made between congenital versus acquired vocal
cord paralysis. Laryngomalacia is the most common congenital laryngeal anomaly
causing stridor, and it must be differentiated from bilateral abductor vocal cord paralysis.
Symptoms usually develop within the first few weeks of life and persist thereafter as a
variable inspiratory stridor. The stridor of laryngomalacia is usually lower pitched and
more pronounced if the patient is supine. The diagnosis is made by flexible laryngoscopy,
which reveals collapse of the epiglottis, the aryepiglottic fold, or the mucosa overlying
the arytenoid, inward toward the glottis. Gastric reflux findings such as edematous
mucosa are commonly found.
Vocal cord paralysis is the second most common cause of stridor in children (Table 52.2)
(10,11). Stridor is the most common presenting symptom of bilateral, and often
unilateral, vocal cord paralysis in children (10). Cyanosis, apneas, feeding difficulties,
cough, and aspiration are other symptoms of vocal cord paralysis. Unilateral cord palsy is
suspected in a child with mild stridor, hoarseness, and a weak, low-pitched cry,
particularly after surgery for patent ductus arteriosus or tracheoesophageal fistula.

TABLE 52.2. SIGNS AND SYMPTOMS OF VOCAL
CORD PARALYSIS



An initial examination may be performed at the bedside or in the clinic with a flexible
nasopharyngoscope after the nose is decongested and anesthetized, without sedation.
After vocal cord paralysis is diagnosed, the patient undergoes direct laryngoscopy and
bronchoscopy under general anesthesia to evaluate the larynx in more detail and to assess
the subglottic and tracheal airway, because subglottic stenosis is the third most common
form of congenital laryngeal malformation. Additional tests should be performed to
determine the cause of the vocal cord paralysis, including magnetic resonance imaging
(MRI) of the central nervous system and computed tomographic (CT) scans of the neck
and chest. Serologic studies are performed to investigate for systemic diseases such as
syphilis.
Etiology
Neurologic disorders are responsible for many cases of vocal cord paralysis in children
(Table 52.3) (10,12,13), the most common being the Arnold-Chiari malformation.
Bilateral abductor cord paralysis with Arnold-Chiari malformation was first recognized in
1961 (14) in two infants with associated meningomyeloceles presenting with stridor.
Arnold-Chiari malformation is characterized by herniation of posterior fossa contents
below the foramen magnum, and is classified into three types based on the degree of
herniation. Hydrocephalus in this condition develops from compression of the brainstem
at the level of the fourth ventricle, preventing egress of cerebrospinal fluid (CSF) from
the fourth ventricle and reabsorption by the arachnoid villi, leading to further brainstem
compression. Herniation due to increased intracranial pressure (ICP) may cause traction
on the vagal rootlets, producing neuropraxia or axonotmesis, which might explain the
occasional reversibility of the vocal cord paralysis. In children who underwent posterior
fossa decompression to correct the internal hydrocephalus, and in those who developed or
were born with a CSF leak associated with meningomyelocele, vocal cord paralysis failed
to develop or improved as ICP decreased. These observations have led to treatment
directed at stabilizing the airway and decreasing ICP. Bluestone et al. (15) found that one
third of patients with vocal cord paralysis, hydrocephalus, and meningomyeloceles had
unilateral cord palsy and required no surgical intervention. In the same series, all cases
with bilateral vocal cord paralysis required tracheotomy. Gentile et al. (10) reported that
tracheotomy was necessary for 11 of 12 patients who had bilateral vocal cord paralysis.

TABLE 52.3. CAUSES OF VOCAL CORD
PARALYSIS IN CHILDREN



The timing of decompression affects the recovery of vocal cord function (Table 52.4)
(15). Six of seven children who underwent surgical correction of the increased
intracranial pressure within 24 hours of onset of airway symptoms recovered vocal cord
function within 2 weeks. In the group who received treatment 1 to 14 days after airway
obstruction, vocal cord paralysis persisted for a period of 4 weeks to 1.5 years.
Tracheotomy may be avoided by early decompression and CSF shunting after intubation.
Even earlier decompression in symptomatic Chiari II malformation patients may prevent
bilateral vocal cord paralysis and severe central hypoventilation, which are associated
with grave prognoses (16).

TABLE 52.4. PERSISTENCE OF VOCAL CORD
PARALYSIS COMPARED WITH THE TIMING OF
SURGICAL CORRECTION OF INCREASED
INTRACRANIAL PRESSURE AND RETURN OF
VOCAL CORD FUNCTION



Congenital idiopathic vocal cord paralysis is frequently reported. The onset of symptoms
and signs in these patients may range from birth up to 8 weeks. Unilateral paralysis is
slightly more common than bilateral paralysis. Recovery can be expected in about 20% of
cases, although it may take several years.
Birth trauma accounts for about 20% of all cases of vocal cord paralysis. Complicated
deliveries requiring cesarean section or forceps delivery account for most injuries. In
either case, traction and stretching of the laryngeal nerves are the proposed mechanism of
injury. The most common reason for an alternative method of delivery is abnormal
presentation of the fetus.
Surgical trauma is a significant cause of vocal cord paralysis in children. It occurs after
cardiac procedures (particularly patent ductus arteriosus repair), tracheoesophageal fistula
repair, mediastinal, and neck surgeries. Onset of paralysis usually occurs immediately
after surgery, and recovery is less frequent than from other causes.
Congenital infections are a rare cause of vocal cord paralysis. Gentile et al. (10) reported
that syphilis was the cause of paralysis in a child who did not regain vocal cord function
despite adequate treatment. There are sporadic reports of possible hereditary patterns of
congenital or childhood vocal cord paralysis (17).
Management
Management of vocal cord paralysis in children should be directed toward the
establishment of a secure airway with minimal detriment to functional integrity.
Recovery can be expected in 48% to 63% of patients (10). Spontaneous recovery has
been reported in idiopathic bilateral cord paralysis after 11 years in a child. Associated
problems such as gastroesophageal reflux should be addressed.
Unilateral Paralysis
Most children with unilateral paralysis have adequate airways. Initially, they may
demonstrate minimal aspiration or weak voices, but most compensate and rarely require
airway intervention. The decision to intervene in the child with unilateral paralysis must
be based on the identification of the cause and the projected outcome. Gentile et al. (10)
reported that no child with unilateral paralysis required tracheotomy and that expectant
management was satisfactory in all cases. Gelfoam injection was performed for two
children with poor cough and aspiration. Type I thyroplasty in which a silastic implant is
placed inside the thyroid cartilage lamina to medialize the paralyzed cord is an evolving
procedure in children, with questions regarding anatomic differences from adults,
efficacy, and long-term results with laryngeal growth. Although an active role in
managing unilateral vocal cord paralysis may be necessary in some children, surgery
should be reserved for those with a laterally positioned paralyzed cord and poor
compensation by the mobile cord. Management usually consists of observation when the
paralyzed cord is found in the paramedian position, or when there is good mobile cord
compensation opposite a lateralized, paralyzed cord.
Bilateral Vocal Cord Paralysis
Bilateral abductor vocal cord paralysis can be an airway emergency, due to the cords
being in the median or paramedian position. The incidence of bilateral cord paralysis is
much higher in injuries related to birth trauma, neurologic abnormalities, and the Arnold-
Chiari malformation compared with other conditions. Tracheotomy is required as an
initial step to stabilize the compromised airway. Bilateral paralysis from surgery or
neurologic disease is more apt to require tracheotomy compared with idiopathic paralysis
(12). More permanent methods of treatment, including arytenoidectomy and lateralization
procedures, usually are postponed for a minimum of 6 months to await functional
recovery.
Lateralization procedures provide an improved airway at the expense of the patient's
voice and airway protection. Arytenoidectomy and arytenoidopexy are irreversible, so the
risks and benefits should be carefully weighed before proceeding with these
interventions.
Narcy and colleagues (18) recommended early lateralization within 6 to 9 months after
diagnosis. Triglia et al. (19) also reported the efficacy of arytenoidopexy for pediatric
patients. By performing arytenoidectomy or arytenoidopexy, they were able to
decannulate 68% of patients.
VOCAL CORD PARALYSIS IN ADULTS
Although the causes of cord paralysis in adults differ from those in infants and children,
many of the diagnostic and management considerations are similar. The left side is
paralyzed more frequently because of the longer and intrathoracic course of the left
recurrent laryngeal nerve. The exception is with anterior approaches to the cervical spine,
in which the right recurrent nerve is far more likely to be injured due to anatomic factors.
Surgical trauma has long been recognized as the most common cause of unilateral and
bilateral vocal cord paralysis (Table 52.5) (20,21 and 22). Neoplastic causes include
bronchogenic carcinoma, other forms of lung cancer, carcinoma of the thyroid gland, and
carcinoma arising in the upper esophagus and larynx. Neurologic diseases causing
laryngeal paralysis include po-liomyelitis, pseudobulbar palsy, amyotrophic lateral
sclerosis, bulbar palsy, and tumors of the central nervous system. Nonsurgical trauma
(including blunt injury such as strangling), thoracic aortic aneurysm, and cardiomegaly
are other causes of cord paralysis. Idiopathic unilateral and bilateral vocal cord paralyses
are consistently reported. Rare incidences of paralysis due to infection (e.g.,
tuberculosis), drug (e.g., cisplatin, organophosphate insecticide), and nasogastric tube or
esophageal stethoscope placement (which may be due to postcricoid inflammation
affecting posterior cricoarytenoid muscle action rather than neural injury), have been
acknowledged. Nonlaryngeal malignancy, surgery-related injuries other than from
thyroidectomy such as thoracic and spine surgery, and intubation injuries are playing an
increasing role in laryngeal paralysis. Unilateral and bilateral vocal fold paralysis from
intubation injuries are likely due to compression of the recurrent nerve as it passes
between the arytenoid cartilage and posterior thyroid cartilage lamina, and may be
prevented by avoiding proximal inflation of the endotracheal tube cuff. A similar
mechanism may explain laryngeal mask airway-induced cord paralysis.

TABLE 52.5. CAUSES OF VOCAL CORD
PARALYSIS IN ADULTS



Evaluation and Diagnostic Tests
Cortical lesions are more difficult to identify because the findings may be subtle and
variable. Lesions of the cortex may result in either spasticity or aphonia. This is not
always reliable, and different findings have been observed. The spasticity found in
cortical lesions is similar to that of upper motor neuron lesions affecting other muscle
groups. Although the cord may be motionless, laryngeal EMG would not demonstrate
denervation.
Lower motor neuron lesions are caused by injuries that directly affect the nerve and
degeneration at the nuclear level. Both abnormalities produce muscle wasting and
atrophy. EMG findings consist of fibrillation potentials and a decreased frequency of
firing in muscle action potentials. Diseases affecting the brainstem include bulbar polio,
amyotrophic lateral sclerosis, syringomyelia, multiple sclerosis, and encephalitis.
Vascular injuries also can affect the vagal nuclei, causing paralysis, although isolated
infarct of the nucleus ambiguus is unusual. Wallenberg syndrome, which is caused by an
infarct produced by occlusion of the posteroinferior cerebellar artery, affects several
brainstem nuclei, including the vagal nuclei. Other signs of brainstem injury include
aspiration, dysarthria, and dysphagia.
Peripheral nerve lesions usually are diagnosed on the basis of patient history and physical
examination. Lesions near the skull base at the level of the nodose ganglion affect both
superior and recurrent branches of the vagus nerve, and patients demonstrate sensory as
well as motor deficits. Chronic aspiration is worsened due to loss of supraglottic
sensation and the afferent contribution to laryngeal reflexes, in addition to vocal cord
paralysis.
Lesions that occur below the nodose ganglion spare the superior laryngeal nerve and
result in cord paralysis caused by recurrent nerve involvement only. There may be only
mild to moderate symptoms of voice change or aspiration with unilateral lesions.
Sensation of the larynx remains intact, and most patients compensate over time, requiring
no treatment. Bilateral recurrent nerve paralysis typically produces a good voice but a
poor airway is manifested inevitably, either progressively or acutely.
Isolated superior laryngeal nerve lesions are uncommon and difficult to diagnose on
physical examination. They may occur after thyroidectomy or occasionally after carotid
endarterectomy. A change in, or decreased range of, pitch may occur due to cricothyroid
muscle weakness from injury to the external branch of the superior laryngeal nerve.
Laryngoscopy reveals a tilting of the larynx with a rotation of the posterior glottis toward
the paralyzed side. The most accurate diagnostic technique is EMG of the cricothyroid
muscle.
In many cases, the cause of vocal cord paralysis is obvious based on the history (e.g.,
recent history of thyroid surgery). If the diagnosis is not obvious, an organized workup
frequently reveals the cause. Computed tomography scans of the base of the skull, neck,
and upper chest that trace the course of the vagus and recurrent laryngeal nerves are
performed. Magnetic resonance imaging of the central nervous system may reveal
responsible lesions. If a thyroid scan is desired for thyroid mass evaluation, it should be
performed before the CT scan because the iodinated contrast agent saturates the thyroid
and prevents adequate radioactive iodine uptake for 4 to 6 weeks. Laryngeal EMG,
panendoscopy, and palpation of the arytenoids are indicated if preliminary tests fail to
elucidate the cause.
Management
Unilateral Vocal Cord Paralysis
Treatment of unilateral paralysis depends on the position of the cord. If the cord is
paramedian, it is likely that no treatment other than observation is necessary.
Compensation by means of a natural tendency for the cord to medialize and through
compensatory activity of the unaffected cord frequently produces a satisfactory voice
without serious aspiration. If functional deficits are tolerable, and it cannot be determined
whether paralysis will be permanent, definitive treatment should be avoided for 6 to 12
months. If function returns, it will occur within this time (21). Electromyographic
findings may mirror functional recovery.
Medialization procedures are indicated for patients in whom the paralyzed cord is widely
abducted, with associated hoarseness or aspiration (20). Irreversible procedures should be
reserved for injuries known to be permanent (e.g., vagus nerve transection during skull
base surgery) or after sufficient time has elapsed to allow for spontaneous resolution.
Electromyographic studies demonstrating fibrillations without voluntary or reinnervation
potentials help to predict lack of functional recovery.
Thyroplasty Type I
Isshiki et al. (23) popularized the type I thyroplasty operation, which places a silicone
block to push a thyroid cartilage window inward against the paraglottic tissues,
medializing the membranous true vocal cord. The procedure is performed with the patient
under local anesthesia, to monitor voice quality, vocal fold position, and avoid airway
obstruction. The airway can be observed during the procedure using a flexible
nasopharyngoscope and video monitor. Variations of the procedure include removing the
window of cartilage and placing the silicone implant in a pocket between the inner
thyroid lamina and perichondrium (Fig. 52.4), and incising the perichondrium to place
the implant just lateral to the paraglottic muscles and arytenoid cartilage. Thyroplasty
systems with sizing tools and prefabricated removable implants are commercially
available, obviating the need for the surgeon to sculpt each implant. This procedure is
reversible at least in the short term, because it is necessary to remove the implant on a
rare occasion because of exertional dyspnea in a patient with chronic lung disease or
partial pneumonectomy.

FIGURE 52.4. Thyroplasty type I. The silastic implant is
placed in a subperichondrial pocket to medialize the cord.
A: The cartilaginous widow has been removed. B:
Dissection of the subperichondrial pocket. C: Implant in
place.



Arytenoid Adduction
Arytenoid adduction uses permanent sutures to anchor the muscular process of the
arytenoid in an adducted position to medialize the vocal cord and close the posterior
commissure. It is comparable with type I thyroplasty by selected objective acoustic and
aerodynamic parameters (24). Type I thyroplasty has been used to augment arytenoid
adduction in cases of atrophic, bowed vocal folds, and arytenoid adduction may
complement type I thyroplasty in those patients with large posterior glottic gaps (25).
Thyroplasty type I implants with posterior projections to displace the vocal process may
achieve satisfactory arytenoid adduction. Variations include adduction arytenopexy,
which requires opening the cricoarytenoid joint and securing the arytenoid to adduct the
vocal cord as well as medialize the posteromedial arytenoid surface to better close the
posterior commissure.
Laryngeal Reinnervation
Crumley has advocated laryngeal reinnervation for restoring voice and glottic
competence using ansa hypoglossi to recurrent nerve anastomosis (26). No laryngeal
motion was appreciated due to synkinesis of reinnervation, but excellent voice quality
was achieved, albeit in a delayed fashion compared with thyroplasty or arytenoid
adduction. When recurrent laryngeal nerve transection is recognized at surgery,
reanastomosis of the cut ends may be expected to yield similar results. Objective voice
measurements have not shown any significant advantage after performing ansa to
recurrent nerve reinnervation plus arytenoid adduction, compared with the results after
the adduction procedure alone (53).
Gelfoam Injection
Gelfoam paste (Pharmacia & Upjohn Co., Kalamazoo, MI) is an excellent augmentation
material for patients in whom recovery is expected but who require immediate
improvement. Injection usually is performed under local anesthesia directly into the
lateral thyroarytenoid muscle to medialize the membranous vocal cord. Resorption occurs
in 6 to 8 weeks and can be repeated until recovery or more permanent procedures are
performed. Other materials that have been successfully used to medialize a paralyzed
vocal fold include autologous fat and autologous collagen.
Teflon Injection
Teflon (Mentor Division, Cudman & Shurtleff, Randolph, MA) paste has been used in
the past as a permanent, injectable material applied as described for Gelfoam but with
significant and irreversible complications such as interference with vocal cord vibration
and destructive Teflon granulomas. It has been supplanted by safer, more efficacious
treatments.
Bilateral Paralysis
In contrast to unilateral vocal cord paralysis, the treatment of bilateral vocal cord
paralysis is directed toward lateralizing one or both cords to improve the airway at the
expense of aspiration and voice quality.
Tracheotomy
Most adults with bilateral vocal fold paralysis require tracheotomies, at times emergently,
to maintain adequate airways. Although there are many potential problems with long-
term tracheotomy, it remains the only treatment for selected patients who may be poor
surgical risks for more definitive procedures. One-way valves allow inspiration through
the tracheotomy tube and expiration past the glottis to produce voice and light cough.
Laryngeal elevation may be hampered and cause dysphagia and aspiration. Permanent
tracheotomy creation by securing skin to the trachea may reduce complications (28).
Laser Cordectomy
Endoscopic removal of one of the vocal cords opens the airway but may result in a
variable quality voice. The results of laser cordectomy may be excellent initially, but as
scarring develops, the airway may become unsatisfactory (29).
Laser Cordotomy
Kashima et al. (30) reported the effectiveness of cordotomy for patients with bilateral
vocal cord paralysis. A posterior gap is created as the posterior portion of the vocal cord
is released from the vocal process and resected with the laser. Obviously, a stable airway
is obtained while maintaining voice quality. Repeat or bilateral procedures may be
performed. The risk of aspiration must be considered as more extensive procedures are
undertaken to improve the patient's airway.
Arytenoidectomy
The Woodman arytenoidectomy is a well-established treatment. In this external
procedure, the larynx is rotated, and the arytenoid on one side of the larynx is identified.
The arytenoid is excised, with the exception of the vocal process, which is left attached to
the vocal ligament. A suture is passed through the vocal process and the thyroid ala and
tightened to provide an adequate airway and a usable voice.
Endoscopic arytenoidectomy is commonly performed using a carbon dioxide laser and
microlaryngeal instruments. Removal of the arytenoid opens the posterior glottis and
frequently provides an adequate airway. Variants of the procedure, by removing lesser
amounts of arytenoid cartilage and displacing the arytenoid by detaching its muscular
attachments, have been proposed to improve voice, decrease posterior glottic scarring,
and prevent redundant mucosa from prolapsing into the airway (31).
Arytenoidopexy
Arytenoidopexy is a technique in which a suture is passed around the vocal process of
arytenoid cartilage and positioned laterally without removing the arytenoid cartilage. This
approach has been used in patients for whom the bilateral paralysis may not be
permanent. Because the procedure is reversible, it may be used in place of tracheotomy,
but gradual long-term medial migration of the vocal cord may occur.
Electrical Pacing
Electrically pacing the posterior cricoarytenoid muscle to coincide with inspiration in
animal and human subjects has been reported to be successful (32). The efficacy and
reliability of long-term pacing remains to be proven, because chronic pacing tends to
produce fibrosis around the active electrodes, progressively increasing resistance to
stimulation.

HIGHLIGHTS
An understanding of neurologic anatomy and possible causes is
essential in evaluating the patient with vocal cord paralysis.
A careful history usually delineates the cause of the hoarseness.
A thorough physical examination is accomplished using a
variety of laryngeal examining devices, including mirrors,
telescopes, and flexible endoscopes. Video documentation can
help in evaluating the response to treatment.
Laryngeal EMG can be performed easily, and in selected
patients it may provide useful information.
Pediatric and adult vocal cord paralysis are different. Children's
paralyses are more frequently neurologic in origin, bilateral,
and predominantly seen in males. The prognosis is generally
better in children than adults.
In most cases of unilateral vocal fold paralysis, no therapy is
needed. When indicated, medialization of the cord is the goal.
Thyroplasty type I or arytenoid adduction are the procedures of
choice.
Most patients with bilateral paralysis require tracheotomies to
have adequate airways. The goal in surgical treatment of
bilateral paralysis is lateralization of one of the cords while
maintaining a serviceable voice.
CHAPTER REFERENCES
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Phoniatr Logop 1974;26:89.
2. Wang RC. Three-dimensional analysis of cricoarytenoid joint motion. Laryngoscope
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3. Ward PH, Berci G, Calcaterra TC. Superior laryngeal nerve paralysis an often overlooked entity.
Trans Am Acad Ophthalmol Otolaryngol 1977;84:7889.
4. Volpi D, et al. Risk factors for intubation injury of the larynx. Ann Otol Rhinol Laryngol
1987;96:684686.
5. Isshiki N. Mechanical and dynamic aspects of voice production as related voice therapy and
phonosurgery. Otolaryngol Head Neck Surg 2000;122:782793.
6. Woo P, Colton R, Casper J, et al. Diagnostic value of stroboscopic examination in hoarse patients.
J Voice 1991;5:231238.
7. Miller RH, Rosenfield DB. The role of electromyography in clinical laryngology. Otolaryngol
Head Neck Surg 1984;92:287.
8. Koufman JA, Walker FO, Joharji GM. The cricothyroid muscle does not influence vocal fold
position in laryngeal paralysis. Laryngoscope 1995;105:368372.
9. Crumley RL. Laryngeal synkinesis revisited. Ann Otol Rhinol Laryngol 2000;109:365371.
10. Gentile RD, Miller RH, Woodson GE. Vocal cord paralysis in children 1 year of age and younger.
Ann Otol Rhinol Laryngol 1986;95:622.
11. Narcy P, Contencim P, Viala P. Surgical treatment for laryngeal paralysis in infants and children.
Ann Otol Laryngol 1990;99:124.
12. Daya H, Hosni A, Bejar-Solar I, et al. Pediatric vocal fold paralysis: a long-term retrospective
study. Arch Otolaryngol Head Neck Surg 2000;126:2125.
13. Cohen SR, Birns JW, Steller KA, et al. Laryngeal paralysis in children: a long-term retrospective
study. Ann Otol Rhinol Laryngol 1982;91:417.
14. Graham MD. Bilateral vocal cord paralysis associated with meningomyelocele and the Arnold-
Chiari malformation. Laryngoscope 1963;73:85.
15. Bluestone CD, Delerme AN, Samuelson GH. Airway obstruction due to vocal cord paralysis in
infants with hydrocephalus and meningomyelocele. Ann Otol 1972;81:778.
16. Pollack IF, Kinnunen D, Albright AL. The effect of early craniocervical decompression on
functional outcome in neonates and young infants with myelodysplasia and symptomatic Chiari II
malformations: results from a prospective series. Neurosurgery 1996;38:703710.
17. Grundfast KM, Milmoe CT. Congenital hereditary bilateral abductor vocal cord paralysis. Ann
Otol Rhinol Laryngol 1982;91:564.
18. Narcy P. Arytenoidopexy for laryngeal paralysis in children. Int J Pediatr Otorhinolaryngol
1995;32(suppl):101102.
19. Triglia JM, Belus JF, Nicollas R. Arytenoidopexy for bilateral vocal fold paralysis in young
children. J Laryngol Otol 1996;110:10271030.
20. Benninger MS, Crumley RL, Ford CN, et al. Evaluation and treatment of the unilateral paralyzed
vocal fold. Otolaryngol Head Neck Surg 1994;111:497508.
21. Woodson GE, Miller RH. The timing of surgical intervention in vocal cord paralysis. Otolaryngol
Head Neck Surg 1981;89:264.
22. Holinger LD, Holinger PC, Holinger PH. Etiology of bilateral abductor vocal cord paralysis. Ann
Otol 1976;85:428.
23. Isshiki N, Morita H, Okamura H, et al. Thyroplasty as a new phonosurgical technique. Acta
Otolaryngol (Stockh) 1974;78:451.
24. Bielamowicz S, Berke GS, Gerratt BR. A comparison of type I thyroplasty and arytenoid
adduction. J Voice 1995;9:466472.
25. Netterville JL, Stone RE, Civantos FJ, et al. Silastic medialization and arytenoid adduction: the
Vanderbilt experience. Ann Otol Rhinol Laryngol 1993;102:413424.
26. Crumley RL, Izdebski K. Voice quality following laryngeal reinnervation by ansa hypoglossi
transfer. Laryngoscope 1986;96:611616.
27. Chhetri DK, Gerratt BR, Kreiman J, et al. Combined arytenoid adduction and laryngeal
reinnervation in the treatment of vocal fold paralysis. Laryngoscope 1999;109:19281936.
28. Wang RC, Perlman PW, Parnes SM. Near-fatal complications of tracheotomy and their
prevention. Head Neck Surg 1989;12:528533.
29. Dennis DPO, Kashima H. Carbon dioxide laser posterior cordectomy for treatment of bilateral
vocal cord paralysis. Ann Otol Rhinol Laryngol 1989;98:930.
30. Kashima HS. Bilateral vocal fold motion impairment: pathophysiology and management by
transverse cordotomy. Ann Otol Rhinol Laryngol 1991;100:717721.
31. Remacle M, Lawson G, Mayne A, et al. Subtotal carbon dioxide laser arytenoidectomy by
endoscopic approach for treatment of bilateral cord immobility in adduction. Ann Otol Rhinol
Laryngol 1996;105:438445.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

53 BENIGN LESIONS OF THE LARYNX
Head & Neck SurgeryOtolaryngology
53




BENIGN LESIONS OF THE LARYNX
ELIE E. REBEIZ
STANLEY M. SHAPSHAY

E.E. Rebeiz and S.M. Shapshay: Department of OtolaryngologyHead and Neck Surgery, Tufts
University School of Medicine, Boston, Massachusetts.

Nodules
Polyps
Cysts
Granuloma
Laryngeal Papillomatosis
Lymphatic and Venous Malformations
Granular Cell Tumor
Chondroma
Neurogenic Tumors
Amyloidosis
Sarcoidosis
Surgical Technique
Chapter References
Proper evaluation of the larynx begins in the office, with a thorough history taking, and a
proper examination. The physician should look for risk factors in the patient's life-style,
as well as vocal use and abuse. Indirect mirror examination, which we routinely perform,
remains an important part of the overall examination. It gives the examiner an excellent
perspective of structure and function of the base of the tongue, hypopharynx, supraglottic
larynx, and true vocal folds. Fiberoptic laryngoscopy and videostroboscopy are essential,
and in special instances, such as with small children, examination under general
anesthesia may be required.
Lesions arising on the true vocal folds result in hoarseness and occasional involvement of
the respiratory symptom. It is important to differentiate neoplastic from non-neoplastic
le-sions of the vocal folds, because non-neoplastic lesions should be treated as
conservatively as possible to preserve vocal function.
Videostroboscopy has become routine and is an essential part of evaluating patients with
laryngeal pathology. Direct telescopic rigid or flexible fiberoptic examination with
videorecording equipment is important for documentation of pathology, as well as for
teaching and research. Endoscopic photography has become easier with the advent of
fiberoptic telescopes with extra fiberoptic bundles designed specifically for photography.
Video documentation is achieved with the camera attached to the beam splitter on the
operating microscope, or on a telescope.
Voice recording is valuable preoperatively and postoperatively both, for following the
patient's progress after treatment and for medicolegal purposes.
NODULES
Vocal fold nodules are usually bilateral and occur most commonly in children and young
adults. There is usually no sex predilection. These nodules most often result from trauma
inflicted on the vocal fold mucosa during excessively forceful vibration presenting as
areas of thickened mucosa overlying the vocal folds. They are usually bilateral and
involve the anterior or middle third of the true vocal fold. The process of nodule
formation usually starts as edema in the submucosa or Reinke space and later becomes
organized fibrous tissue.
On laryngeal examination, the lesion appears shiny, with a wide base (Fig. 53.1 and Fig.
53.2). They usually present on the junction between the anterior and middle third of the
vocal fold. The initial, preferred treatment is voice therapy and a period of voice rest.
Surgery is required when the lesion is well organized or fibrotic or if there is any
suspicion about a malignancy. In general, however, 6 months of voice therapy is
recommended before surgery is considered. Photo documentation by videolaryngoscopy
or by still photography is helpful so that an accurate comparison can be made during
subsequent examinations. Unilateral nodules or asymmetric nodules are usually
intracordal cysts and can be recognized easily by video laryngoscopy and stroboscopy.
The contralateral vocal fold usually has some degree of contact injury and some fibrosis.

FIGURE 53.1. A: Left true vocal fold nodule.B:
Immediately following excision using micro-scissors. C:
Four weeks after surgery.



FIGURE 53.2. Endoscopic view of intracordal cyst of
the true vocal fold, being removed submucosally.



In children, the larynx should be visualized by indirect or direct fiberoptic laryngoscopy
to rule out other lesions, such as recurrent respiratory papillomatosis. Nodules in children
are usually poorly demarcated and will resolve spontaneously as vocal habits change;
however, removal is warranted only when they become large and thickened with marked
deterioration in voice quality and impaired communicative ability.
POLYPS
Laryngeal polyps usually present as pedunculated or sessile lesions involving the middle
half, anterior half, or entire vocal fold. They are usually unilateral and appear at the free
edge of the vocal fold, usually between the anterior and middle thirds of the true vocal
fold. There is no sex predilection, and these polyps can occur in any age group. They are
the most common benign lesions of the adult larynx. There are two types of laryngeal
polyps: mucoid and angiomatous. The mucoid type is usually a reflection of an
inflammatory process arising in the subepithelial layer of loose connective tissue,
commonly referred to as the Reinke space. This subepithelial space ends abruptly at the
junction of the squamous and respiratory epithelium on the upper surface of the vocal
fold and in the immediate subglottic area, thereby dictating the location of nodules and
polyps on the free edge of the vocal fold. This process of chronic edema may be
localized, as in a pedunculated polyp, or it may be diffuse, as in polypoid changes or
Reinke space edema. Localized polyps may have varying degrees of vascularity,
suggesting an angioma; some, as a result of their chronicity, may have areas of hyaline
degeneration, suggesting amyloid deposits. Women are most commonly affected with
bilateral vocal fold polyps or polypoid change. They are usually heavy smokers and vocal
abusers. Hypothyroidism is associated with development of vocal fold edema and should
be suspected, particularly if other signs and symptoms are present.
Mucoid polyps are translucent, grayish lesions, with little vascularity, whereas
angiomatous polyps are dark red, protuberant, and multinodular. Transitional forms exist
and depend on the extent of the inflammatory response and fibrosis. The localized
unilateral pedunculated polyp usually arises as a result of acute vascular disruption, in
most cases a result of severe vocal abuse. This possibly causes acute submucosal
bleeding followed by formation of a local organized hematoma. In the acute setting, most
of these patients present with aphonia for a few days, then the hematoma gradually
resolves with voice rest. Continued chronic irritation secondary to vocal abuse leads to
inflammatory changes and fibrosis.
Surgical removal of vocal fold polyps by microlaryngoscopic techniques is considered
standard treatment and should be recommended in most cases, particularly if the patient
has a history of smoking. Although it is unlikely that polyps represent a malignancy,
there can be areas of dysplastic epithelium, particularly on the undersurface of large
floppy polyps. Precise removal with preservation of underlying submucosa and muscle
can be accomplished with microlaryngeal instruments.
An incision is made on the superior lateral aspect of the vocal fold, carefully avoiding the
vibrating edge. The microspot (250 m spot size) CO
2
laser is used to make an incision at
power settings of 2 to 3 W, with intermittent pulses of 1/10 second, encountering the
polypoid material in the submucosa. The gelatinous fluid is removed with microsuction,
carefully avoiding trauma to the mucosa. A microflap then is developed using 1-mm cup
forceps and a microlaryngeal probe or elevator to free loculi of the thick myxomatous
material present within the lesion. This step should be performed without traumatizing
the healthy mucosa. The plane of dissection is superficial and should not involve the
vocal ligament. A small amount of gelatinous material can be left over the vocal ligament
to provide a gliding surface or a new submucosal layer for the mucosal cover. The excess
mucosa of the microflap is trimmed conservatively using up-cutting microlaryngeal
scissors. The mucosal edges are reapproximated using fibrin glue adhesive. As in any
laryngeal surgery, mucosal preservation is the key to good vocal results regardless of the
technique used. Postoperatively, the patient should abstain from smoking and avoid vocal
abuse. Postoperative care is similar to patients who have more localized polyps removed.
With this technique both vocal folds are treated at one sitting; good return of voice occurs
in 3 to 4 weeks. Video stroboscopy documentation is an essential part of postoperative
evaluation and follow-up in many of these patients. Treatment of coexisting
gastroesophageal reflux disease is very important to prevent irritation, inflammatory
changes, and poor healing.
CYSTS
The supraglottic larynx is the most common site of laryngeal cysts, occurring most
frequently where mucus-secreting glands are abundant. Although mucous retention cysts
are the most common type of cysts affecting the larynx, embryonal cysts are possible.
These are congenital cysts that usually arise in the aryepiglottic fold or lateral pharyngeal
wall, possibly related to branchial arch remnants of the third cleft. These cysts may
become quite large, presenting as airway obstruction in the newborn or as a laryngeal
mass in the adult.
It is relatively common to find small asymptomatic mucous retention cysts in the
valleculae, base of tongue epiglottis, or aryepiglottic folds. On occasion, large retention
cysts originating in the supraglottic larynx may cause airway obstruction, particularly in
the pediatric larynx. They also may be found in the true and false vocal folds and are
thought to originate from minor salivary glands within the larynx. Cysts arising in the
ventricle and in the false and true vocal folds are usually not large or obstructive and
usually present with hoarseness as their presenting symptom.
Cysts in the supraglottic larynx or valleculae can be easily excised if small, or unroofed
and marsupialized if large, using the CO
2
laser. Healing is usually excellent, and
reepithelialization is complete with no scarring. Cysts of the true vocal folds are usually
intracordal and should be dissected carefully by using microsurgical techniques and
excised completely, preserving overlying mucosa. If excision is incomplete, the
recurrence rate is high. Imprecise removal of small vocal fold cysts may cause permanent
vocal dysphonia as a result of scarring and stiffness of the normal mucosal wave.
The incision should be made on the superior lateral surface of the fold, not to interfere
with the vibrating medial edge. The cyst can be dissected submucosally using blunt
probes and elevators and spreading with alligator microforceps (Fig. 53.2). The mucosal
flap is returned in position and usually adheres in place. Mucosal thickening of the
opposite vocal fold resolves spontaneously after the cyst is removed.
GRANULOMA
Vocal fold granulomas usually arise in the region of the vocal process or body of the
arytenoid (Fig. 53.3). The patient frequently has a history of gastric reflux or previous
traumatic or prolonged endotracheal intubation. Contact ulceration often precedes
granulation formation and is associated with vocal abuse. Patients with high-risk
occupations include auctioneers and factory workers, who must communicate in a noisy
environment. The most common symptom is hoarseness; however, irritative symptoms
such as frequent throat clearing, deep-seated sore throat, and a foreign body sensation are
common as well, depending on the location of the granuloma. If the granuloma is on a
narrow pedicled base, a ball-valving phenomenon may occur with occasional aphonia and
coughing spells. Granulomas may be bilateral, particularly if intubation trauma is the
cause, but they are usually unilateral with a corresponding contact irritation on the
opposite vocal process. Rarely, airway distress can occur with large lesions; however,
this is more likely with subglottic granulomas from traumatic endotracheal intubation in
patients on ventilator support.

FIGURE 53.3. Large granuloma involving the vocal
process of the left arytenoid.



The best approach in treating laryngeal granulomas is to eliminate the cause for the
chronic irritation. Patients usually require voice therapy and should be treated for
gastroesophageal reflux, even if clinical symptoms and radiologic studies are negative.
Testing with the pH probe should be part of the workup of vocal fold granulomas. Most
patients can be cured with voice therapy if the etiology is hyperkinetic speech. If
gastroesophageal reflux disease is present and treated aggressively, complete resolution is
possible. Medical treatment of idiopathic granuloma formation or chronic traumatic
granuloma using antibiotics or short courses of inhalational or systemic steroids is usually
not successful but should be tried. The patient should be counseled about possible
spontaneous resolution or coughing the granuloma out, with some hemoptysis. In cases of
chronic granuloma with hoarseness, the patient is often concerned about the possibility of
cancer and must be reassured.
If surgical treatment is required, the CO
2
laser is ideal for excision. Coupled to an
operating microscope, the laser can be used to excise the granuloma precisely, followed
by vaporization of any remaining granulation tissue. Care should be taken not to expose
the underlying arytenoid cartilage to prevent chondritis. Consideration should be given to
injecting depot steroids at the base of the resected granuloma. In general, granuloma
formation should be viewed as a medical problem rather than a surgical problem, with
chronic inflammation as the pathologic process. Postoperative medical management is
important and consists of voice rest for a week, followed by modified voice use and
systemic broad-spectrum antibiotics for a period of 3 to 4 weeks. Systemic steroids are
administered until healing of the surgical site is complete. Variable success has been
obtained with inhalational steroids and is not routinely recommended.
In recent years, localized injections of botulinum toxin type A have been reported in a
number of patients. Laryngeal granulomas were successfully treated in six patients who
underwent injection of the affected vocal folds. Botulinum toxin type A is believed to
prevent forceful closure of the arytenoids during phonation and coughing. Localized
injection of the neurotoxin can be performed as an initial treatment, and as an alternative
treatment in patients who do not respond to standard therapy or who are poor surgical
candidates (1).
LARYNGEAL PAPILLOMATOSIS
Recurrent respiratory papillomatosis is a condition that affects mucous membranes of the
respiratory tract. It is characterized by multiple and recurrent squamous papillomata,
most commonly involving the larynx, but other areas of the upper and lower respiratory
tract may be involved, causing hoarseness and some degree of respiratory obstruction,
particularly in children.
These lesions are thought to be of viral etiology (2), and are the most common benign
laryngeal tumors (3). This condition may develop in all age groups, but is more prevalent
in children and less common in individuals over 30 years of age. It is believed that
transmission of human papillomavirus (HPV) to the child occurs in the birth canal. Shah
and Kashima (4) found only one case of juvenile-onset respiratory papillomas in a child
born by cesarean section in their review of 109 cases. The risk of transmission of HPV
infection from mother to child was estimated to be in the range of 1:80 to 1:500. Total
remission may sometimes take place at puberty; however, this is not always the case.
On gross inspection, the papillomas appear in a multinodular pattern and may be sessile
or exophytic (Fig. 53.4). Histologically, the lesions are made of papillary projections and
hy-pervascular fibroconnective tissue covered by hyperplastic squamous epithelium that
shows maturation. Cellular atypia is the rule rather than the exception, possibly leading to
misdiagnosis of carcinoma in situ or invasive squamous cell carcinoma. Histologic
differentiation from early carcinoma may sometimes be difficult. The presence of atypia
is believed to be associated with malignant transformation (5). Ultrastructural and im-
munohistochemical studies implicate HPV in the etiology of this disease. Light and
electron microscopic evidence of viral etiology has been documented, and HPV was
identified in respiratory papilloma (2). Specific subtypes of HPV-6 have been correlated
with the extent and the severity of the disease, such as spread of the papillomas into the
trachea and lungs.

FIGURE 53.4. Laryngeal papillomas involving the right
and left posterior glottis and arytenoids.



Papillomatosis of the larynx, the most common site of these tumors, is a serious and
difficult problem in the pediatric population. Hoarseness is the most common early
symptom, followed by airway obstruction and respiratory difficulty. The vocal folds and
the subglottic larynx are the most common laryngeal sites. Nasopharyngeal, subglottic,
tracheal, and bronchial papillomas are thought to be due to contamination from glottic
and supraglottic lesions. Lower airway contamination is seen commonly after a
tracheotomy, which therefore should be avoided if possible. Pulmonary papillomas are
rare, but if they are present they can cause severe complications such as hemorrhage and
abscess formation (Table 53.1). Laryngeal papillomas presenting in adults seem to be less
aggressive than the juvenile form, but the remission rate is unpredictable. Papilloma
growth may be rapid and dangerous to airway patency during periods of hormone change,
such as during pregnancy. Malignant degeneration of laryngeal papillomas is rare and
usually is associated with a history of radiotherapy, tobacco abuse, or both.

TABLE 53.1. BENIGN LESIONS LIKELY TO
PRESENT AS AN EMERGENCY



No therapy has been satisfactory in treating this disease. However, spontaneous
remissions can occur. Frequent excisions are recommended as required to avoid a
tracheotomy and to allow the child to develop good phonation, preserving vocal fold
structure and function. The CO
2
laser, however, has been helpful in the palliation of
lesions present in the larynx, pharynx, upper trachea, and nasal and oral cavities, allowing
long periods of disease-free intervals in many cases. A tracheotomy should be avoided
whenever possible to allow the child to develop normal speech and to avoid spread to the
lower airway.
Laser excision of laryngeal papillomas is performed at a power setting of 2 to 8 W (using
impact spot sizes of 0.3 to 0.8 mm) in an intermittent mode (0.1- to 0.5-second
exposures). The lesions are vaporized until healthy mucosa is reached, without violating
the Reinke space or vocal ligament. Lesions over the anterior commissure are vaporized
carefully, leaving 1 to 2 mm of mucosa to prevent the formation of a web. The laser char
should be carefully removed with suction or a wet sponge.
It is difficult to compare the effectiveness of the different therapeutic modalities because
of the unpredictable and variable behavior of the disease. Microlaryngeal techniques
using forceps, cryosurgery, microcauterization, and the CO
2
laser all have been
successfully used for the control of papillomas. Other forms of therapy, such as vaccines,
chemotherapy, and hormonal therapy, have been unsuccessful thus far. Trials of therapy
with interferon (6) and photodynamic therapy (7) have been successful in achieving some
degree of disease regression, but have not been curative. New advances in the treatment
of laryngeal papillomatosis include the use of cidofovir (Vistide) and indole-3-carbinol.
Pransky and colleagues reported on the use of cidofovir, an acyclic nucleoside
phosphonate analogue, for the treatment of laryngeal papillomatosis. Intralesional
injections seem to benefit patients with severe respiratory papillomatosis, requiring
frequent laryngoscopy treatments with CO
2
laser therapy. Microsuspension laryngoscopy
was performed with intralesional injection of cidofovir in conjunction with mechanical
debulking of papillomas, and a dramatic response was reported at follow-up (8).
Moreover, indole-3-carbinol was used by Rosen and colleagues to treat 18 patients with
laryngeal papillomas, without major complications. They reported encouraging results.
Thirty-three percent (6 of 18) of the patients had a cessation of their papilloma growth
and have not required surgery (9).
LYMPHATIC AND VENOUS MALFORMATIONS
Venous and lymphatic malformations in children are uncommon tumors that most
frequently occur in the head and neck. Symptoms associated with malformations of the
larynx include hoarseness and dyspnea, which may worsen as a result of enlargement of
the mass after infection, hemorrhage, or trauma.
Mulliken and Glowacki (10) divided vascular lesions into two groups. Hemangiomas
refer to lesions with increased mitotic activity that are characterized by rapid postnatal
growth, followed by very slow involution; malformations refer to lesions that are inborn
errors of vascular morphogenesis and grow proportionately with the child.
Histologic examination of lymphatic malformations reveals endothelial cell hyperplasia
and an increased number of mast cells during the proliferative phase and a normal mast
cell count in the involutional phase. In contrast, venous malformations grow in proportion
to the child, fail to regress, may fluctuate in size, and are associated with normal
endothelial cell turnover and mast cell count.
There are many therapeutic options, including lasers, corticosteroids administered
systemically and into the lesion, -interferon, and the prospect of new inhibitors of
angiogenesis. The role of laser therapy in the management of patients with lymphatic
malformations has been reported by many, and different laser wavelengths have been
used, including the CO
2
la-ser (11), the argon laser (12), and the neodymium:yttrium-
aluminum-garnet (Nd:YAG) laser (13,14).
Venous malformations of the head and neck rarely involve the larynx. In a review of 32
patients, only five had laryngeal involvement (13) (Fig. 53.5). The lesions are low flow
and can either be solitary or associated with other pharyngeal or oral lesions. A
tracheotomy alone is a good choice for airway maintenance when other treatment options
are not available. Other therapies include resection, embolization, cryotherapy,
electrodesiccation, corticosteroid administration, -interferon injection, and the injection
of sclerosing agents. All these options, however, are associated with the potential for
major morbidity and are not particularly successful in controlling the malformation while
protecting the airway.

FIGURE 53.5. Low-flow venous malformation of the
larynx involving the posterior commissure. Observation
of a lesion in this location is advisable if the patient is
asymptomatic because of the potential scarring following
attempt at excision or laser photocoagulation.



The Nd:YAG laser treatment of venous malformations of the larynx should be planned
and performed in several stages, depending on the location and size of the lesion and the
age of the patient. The laser is set at 30 W and 1-second exposure in a defocused
noncontact mode. The risk of necrosis of surrounding normal tissue and scarring is higher
when the total laser energy used is excessive. It is preferable to undertreat a benign
lesion, with the intent of achieving regression in several stages, rather than damaging
healthy mucosa. When the Nd:YAG laser is used for coagulation of these lesions, pain is
minimal, even if swelling and necrosis occur. Systemic steroids are generally
administered unless a tracheotomy is performed for airway protection. Other surgical
procedures include laryngofissure and excision, but these procedures carry the risk of
bleeding, prolonged postoperative edema with airway obstruction, and voice change.
Clinical evaluation of the interstitial Nd:YAG laser therapy of hemangiomas and vascular
malformations showed a high effectiveness (15). Patients with large hemangiomas and
vascular malformations were treated with interstitial Nd:YAG laser therapy (power
density, 1,300 to 3,300 W/cm
2
), partly complemented by a noncontact mode Nd:YAG
laser light application (energy density, 1,000 to 2,500 J/cm
2
), under ultrasonographic and
manual control. Nearly 60% of the patients showed a complete clinical regression,
whereas 33 (35.8%) had a partial regression, and 4 patients had an unsuccessful treatment
with the laser.
Capillary type hemangiomas involute spontaneously by the time the patient reaches 7
years of age, and treatment may not be necessary. Complications such as bleeding,
compression symptoms, and pain warrant intervention. Histopathologic examination
should be performed only when the diagnosis is uncertain because hemorrhage is a major
concern, particularly in the airway. Subglottic hemangiomas in children are sessile
lesions and may be associated with cutaneous hemangiomas. They are red or dark blue,
compressible, and unilateral. The presenting symptom is airway distress or stridor, and
treatment is chosen according to the severity of symptoms. Treatment options include
systemic steroids and tracheotomy. If spontaneous involution (usually at age 1) does not
occur, endoscopic resection with the CO
2
laser can be done. Excellent results and low
morbidity have been reported when using the CO
2
laser. Ablation with a CO
2
laser,
although useful for small, solitary mucosal lesions, may result in scarring and laryngeal
stenosis, particularly in cases of large, circumferential lesions of the subglottic space
(11). The Nd:YAG laser, although ideal for vascular tumors, is not recommended for
subglottic hemangiomas, because these lesions are not vascular. The depth of penetration
of the Nd:YAG laser presents a serious risk to the infant's larynx and trachea, with
potential stricture formation and tracheal perforation.
New advances in the treatment of hemangiomas include ci-dofovir, which was found to
elicit a marked protection against hemangioma growth in newborn rats (16). Treatment
with ci-dofovir at 25 mg/kg once a week resulted in a complete suppression of
hemangioma development, which is believed to be due to an antitumor or antiangiogenic
effect. Cidofovir may be further explored for the treatment of vascular tumors,
particularly life-threatening juvenile hemangiomas.
GRANULAR CELL TUMOR
Granular cell tumors are relatively uncommon benign laryngeal lesions thought to
originate from Schwann cells. They are primarily identified in the skin and mucous
membranes of the head and neck area. There are two types of granular cell tumors:
mucosal granular cell tumor and congenital epulis or gingival giant cell tumor.
Granular cell tumors are characterized by slow, painless growth. The tongue is the most
common site of origin (17). The larynx is an uncommon location for these tumors,
accounting for approximately 3% of cases.
The gross appearance of the granular cell tumor is that of a well-circumscribed, firm,
grayish yellow mass. The mass is solitary, polypoid, sessile, papillary, or cystic. It
appears either as a yellowish mass deep within the musculature of the larynx, or a
granular protuberant tumor on the surface of the vocal fold, located most commonly on
the posterior two thirds of the true vocal fold or arytenoid. The tumors are usually 1 cm
or smaller in diameter, and hoarseness is the presenting symptom.
Histologic examination demonstrates large polygonal cells with distinct borders arranged
in nests, strands, or sheets within bands of fibrous tissue. The tumor typically infiltrates
into the surrounding structures, and there is no distinct capsule. Nuclei are typically
hyperchromatic and bland, although a mild degree of nuclear pleomorphism may be
present. Mitotic figures are rare. The abundant, eosinophilic cytoplasm is filled with
granules of varying sizes. These granules are the defining characteristic of the granular
cell tumors and are believed to represent lysosomes in varying stages of fragmentation. In
some cases, formation of keratin pearls may occur, a condition referred to as pseudo-
epitheliomatous hyperplasia. This feature is most apparent in the larynx and may be
confused with a squamous cell carcinoma if the underlying granular cell tumor is not
appreciated. A biopsy of sufficient depth can demonstrate the underlying granular cell
tumor and is therefore essential in obtaining the proper diagnosis.
Treatment of granular cell tumors is complete excision. Endoscopic removal, most often
with the use of a laser, is an acceptable approach for small tumors. However, larger
tumors may require laryngofissure or conservative resection. The recurrence rate in a
large series was 8% (17), and all the recurrences followed resection with positive
margins, but the majority of tumors with positive margins did not recur. Radiation
therapy is not considered appropriate treatment for these lesions.
CHONDROMA
Tumors of the laryngeal cartilage are rare. Affected patients are usually 40 to 60 years of
age, and men are affected four times as often as women. Histologically, some tumors
may simulate chondrosarcoma, showing cellular atypia with irregular and hyperchromatic
nuclei (18).
In the larynx, chondromas originate from the epiglottis, cricoid, arytenoid, or thyroid
cartilages. The main symptoms are hoarseness, dyspnea, and dysphagia in that order, and
chondromas may be insidious because of their slow growth rate. A sensation of pressure
or fullness and frequent throat clearing also may be present.
Chondromas are composed mostly of hyaline cartilage and are seen most commonly as a
smooth, firm, round submucosal or nodular mass arising from the subglottic larynx or
from the internal or external aspect of any of the laryngeal cartilages. Occasionally,
chondromas of the cricoid, thyroid, or tracheal cartilages may present as a hard neck mass
attached to these cartilages. Plain soft-tissue radiographs, laryngeal tomograms, and
computed tomography (CT) scans clearly delineate the tumors and define their extent.
Diagnosis can be made with a relatively small biopsy specimen by identifying normal
cartilage cells in clusters and with a normal-appearing nucleus. Because these masses are
hard, biopsy may be difficult. The CO
2
laser can be used to obtain a wedge biopsy
through the tumor.
The treatment is complete surgical excision through either a thyrotomy or lateral
pharyngotomy approach, depending on the site of the tumor. Subglottic chondromas are
best exposed with a laryngofissure while the chondromas of the posterior aspect of the
cricoid, arytenoid, or thyroid cartilages are best approached by an external approach with
or without a pharyngotomy. Endoscopic removal of chondromas is not indicated unless
the tumor is extremely small. Total laryngectomy should be reserved for extremely large
tumors or recurrent poorly defined growths. It may be difficult for the pathologist to
determine the difference between chondroma and chondrosarcoma; however, in general,
conservative operations are indicated because the growth rate is extremely slow. If a
malignant diagnosis is made, total laryngectomy is indicated.
NEUROGENIC TUMORS
Neurogenic tumors of the larynx are extremely rare (19). They can affect all age groups
and are slightly more common in women, and they account for 0.1% of benign laryngeal
lesions. Schwannomas, also called neurilemmomas, originate in Schwann cells, which
cover the nerve fibers outside the central nervous system. They are usually solitary and
well capsulated. They are benign and slowly growing. Malignant sarcomatous
degeneration rarely occurs. Neurofibromas associated with von Recklinghausen disease
are often multiple and part of neurofibromatosis, and they are characterized by
proliferation of sheath cells and nerve fibers, as well as caf au lait spots. They are not
capsulated and are usually nodular and diffuse. If the diagnosis of neurofibromatosis is
made, a complete workup should be done to look for other lesions.
These tumors are usually submucosal and smooth in consistency, located in the
aryepiglottic folds, extending into the supraglottic space. They also can involve the
arytenoids or the ventricular fold. The most common nerve of origin is the internal
branch of the superior laryngeal nerve, after it enters through the thyrohyoid membrane.
They can be seen by direct or indirect laryngoscopy. CT scan of the larynx will delineate
the lesion accurately.
The presenting symptoms of neurogenic tumors are those of a slow-growing lesion.
There is usually a sensation of fullness, accompanied by voice changes, frequent throat
clearing, and a sensation of a lump in the throat. Cough and respiratory distress will
follow, characterized by an inspiratory stridor. Imaging of these lesions is best done via
CT or MRI scan.
Biopsy of these tumors should be performed endoscop-ically by incising the mucosa and
taking a deep submucosal specimen. If difficulty is encountered, however, an exter-nal
approach is necessary. Schwannomas are radioresistant, and surgery is the treatment of
choice. Different external approaches are available, such as external thyrotomy and
lateral pharyngotomy. Small tumors may be removed through an endoscopic approach.
AMYLOIDOSIS
Amyloid is an uncommon problem, and its occurrence in the head and neck region has
ranged from 12% to 90% in several large series. The larynx is the most common site of
localized amyloid deposition in the respiratory tract, followed by the trachea, bronchus,
and tongue (20). Amyloid can be either local or systemic, primary or secondary. Local
disease involves one site (i.e., the larynx) or an organ system (i.e., the respiratory tract);
systemic disease includes more than one organ system. Patients with systemic amyloid
tend to have diffuse organ system involvement and a higher percentage of head and neck
involvement (up to 90%); they may be relatively asymptomatic until involved tissue
enlarges considerably. The larynx and trachea are frequently the targets of local
amyloidosis. Other common sites in the head and neck include the tongue and thyroid
gland, salivary glands, and pharynx.
Laryngeal amyloid is an uncommon finding, accounting for fewer than 1% of all benign
laryngeal lesions, despite the fact that the larynx is the most common symptomatic site
for amyloid in the head and neck. It is important to differentiate true amyloid from the
pseudoamyloid of the vocal folds seen in the common vocal nodule. Pseudoamyloid
contains no fibrils and is composed of hyaline degeneration of ground substance.
Presenting symptoms include hoarseness, stridor, globus, and dysphagia. Because
amyloid rarely breaks through the mucosa, hemoptysis is an uncommon finding. The
supraglottis is involved most frequently (vestibule, false vocal folds, aryepiglottic folds),
followed by the glottis (true vocal folds), and subglottis (20). Up to one third of amyloid
with laryngeal involvement may involve the trachea. Laryngeal amyloid is almost always
localized and of the AL type; it is rarely systemic. Although localized to the respiratory
tract, the submucosal nodules tend to be diffuse and infiltrative. It is less common to have
a discrete nodule. The clinical course is often benign, with higher morbidity associated
with multiple site involvement.
On gross appearance, amyloid has a characteristic waxy gray to yellow-orange
appearance, with a rubbery or firm texture. Definitive diagnosis, however, is made
histologically. Hematoxylin and eosin staining shows an extracellular, amorphous pink
material. The classic apple-green birefringence is seen with Congo red stain under
polarized light. Electron microscopy reveals characteristic linear, nonbranching fibrils in
-pleated sheets.
Treatment of amyloid deposits is by conservative removal, and prognosis is usually good.
Steroids and antimetabolites have not been helpful. Recurrence of the amyloid deposits is
possible, particularly in the patients with diffuse submucosal involvement (20).
Surgical removal of the lesions is generally effective, either endoscopically or through a
laryngofissure. Use of the CO
2
laser has been quite effective. Repeated surgical excision
is often needed in patients with multiple airway site involvement. Mitrani and Biller (21)
reported a case of supraglottic involvement that required a supraglottic laryngectomy.
SARCOIDOSIS
The larynx may be involved in 1% to 5% of patients with sarcoidosis (22). The epiglottis
is the most common site of laryngeal involvement, followed by the aryepiglottic folds,
arytenoids, false vocal folds, and subglottis (Fig. 53.6). The true vocal folds are rarely
involved. Mucosal ulceration is rare, with the lesion presenting submucosally as a diffuse
or localized growth.

FIGURE 53.6. Sarcoid lesion involving the supraglottic
larynx.



Laboratory studies may be helpful in the diagnosis. Liver enzymes may be elevated,
especially aspartate aminotransferase and alkaline phosphatase levels. Other findings
include elevated angiotensin-converting enzyme levels, cutaneous anergy, elevated
sedimentation rate, eosinophilia, hypercalcemia, hypercalciuria, and
hypergammaglobulinemia.
Small noncaseating granulomas are seen on histologic examination and are characteristic
but not diagnostic of this con-dition. Other conditions must be ruled out, such as fungal
or mycobacterial infection and a nonspecific granulomatous process.
The differential diagnosis of laryngeal sarcoidosis includes other granulomatous
processes of unknown pathogenesis, infectious granulomatous diseases, inhalant
granulomatous processes, hypothyroidism, and malignant processes. Squamous cell
carcinoma should be included in the differential diagnosis because patients can have
similar findings on examination.
Treatment should be aimed at maintaining an airway, and the disease process tends to
regress spontaneously. Excision of obstructing lesions endoscopically is indicated.
Steroids may help in relieving the edema and can be effective in obtaining resolution.
SURGICAL TECHNIQUE
Good exposure is essential for proper excision of benign laryngeal lesions. It is preferable
that the entire length of both vocal folds be visualized and evaluated. Jako (23) and
Kleinsasser (24), in the late 1960s, introduced large-bore fiberoptic laryngoscopes, used
with the operating microscope with a 400-mm lens. Operative microlaryngoscopy is
presently the method of choice in the evaluation and treatment of benign laryngeal
disorders (Table 53.2 and Table 53.3). Microlaryngeal scissors, cup and alligator forceps,
and probes are used. As a general rule, the largest fiberoptic laryngoscope to fit the
patient's larynx should be used for both diagnostic and therapeutic laryngoscopy. For
exposure of the anterior commissure, a more triangular tip is preferable to an oval one.

TABLE 53.2. DIAGNOSIS BENIGN
LARYNGEAL LESIONS



TABLE 53.3. COMPLICATIONS
MICROLARYNGOSCOPY



The operating microscope allows excellent depth perception and good magnification, and
it permits accurate assessment of the level of resection. The usual magnification setting
on the microscope is 16 times. For smaller lesions, however, magnification of 25 times
may be necessary. Working at the higher magnification, however, presents a technical
problem because the slightest hand tremor is magnified and the overall perspective for
the operating field may be distorted, leading to an uneven plane of dissection.
The surgical excision of vocal fold lesions with the CO
2
laser is somewhat controversial.
It is debatable whether to use the cold technique with microscissors and forceps or laser
removal. Although laser excision of benign laryngeal lesions is bloodless and precise, if
excessive heat is used, scarring may occur. In order to minimize heat transmission,
wattage is reduced to 2 to 3 W (250 m spot size), and the laser is fired intermittently.
Irrigation with cold saline is frequently done, and the microlaryngeal suction is kept close
to the vaporization site, removing the hot steam of vaporization to minimize collateral
damage.
In order to determine the potential harmful effect of the CO
2
laser, Benninger compared
the use of the cold microdissection to the CO
2
laser for excision of benign lesions of the
vocal folds (25). He assigned 37 patients with benign laryngeal lesions to two groups, and
randomly selected them to undergo excision of benign lesions of the true vocal fold,
using microdissection in one group and CO
2
laser in the other. He evaluated the voice
after surgery with perceptual analysis, videostroboscopy, and acoustic and aerodynamic
measures, and found no statistical difference in voice quality after surgery.
An alternative to laser excision or vaporization is a completely cold technique using
microscissors and forceps. It is mandatory that the finest 1-mm cup forceps and scissors
be used for this technique because delicacy and precision are necessary for successful
outcome. Either the entire nodule with overlying mucosa is excised or an attempt is made
to raise the overlying epithelium as a flap before the fibrous nodule is removed. A
shortcoming with any cold technique is bleeding that, although slight, obscures the
operative site as soon as the first cut is made. This problem is not as significant with well-
defined, exophytic nodules, which can be removed with one cut, without the microflap or
dissection technique.
Voice care after surgery is essential. The patient should abide by strict voice rest for the
first week, soft vocalization on the second week, and gradual resumption toward normal
speech in the third postoperative week. Postsurgical care includes inhalation of cool mist
during the first week to prevent drying of the mucosa, permitting better healing. Voice
therapy is encouraged to maximize good voice results. In general, a mild diet is
recommended the first week, avoiding spicy food. Proton pump inhibitors are advisable
after surgery, especially if gastro-esophageal reflux is present. Hydration is stressed, and
drying agents such as antihistamines are avoided. Antibiotics are not routinely
administered.

HIGHLIGHTS
Microlaryngoscopy is the best method for detection and
treatment of benign lesions.
A large laryngoscope should be used. A laser should be used
only if optimal exposure is possible.
Videostroboscopy and photo documentation are important for
records, research, and teaching.
Nodules are usually bilateral, and they are most common in
children and young adults.
Polyps are pedunculated or sessile lesions found on the anterior
and middle thirds of the true vocal fold. The two types are
mucoid and angiomatous.
The most common site for cysts is the supraglottis. Treatment is
via CO
2
laser marsupialization or excision.
The most common site for granulomas is the vocal process. The
patient should be treated for gastric reflux and receive
endotracheal intubation during surgery.
Laryngeal papillomatosis affects the mucous membranes of the
respiratory tract, and can be multiple and recurrent. The upper
and lower respiratory tract may be involved. HPV is a possible
cause.
Lymphatic and venous malformations rarely present in the
larynx. Treatment options include resection, embolization,
cryotherapy, electrodesiccation, cortico-steroid administration,
and the injection of sclerosing agents. Satisfactory results have
been achieved with the Nd:YAG laser.
Granular cell tumors are uncommon benign laryngeal lesions.
The most common sites of occurrence in the head and neck
region include the tongue and soft tissues, and posterior two
thirds of the true vocal fold or arytenoid.
Chondromas are rare lesions that may simulate
chondrosarcoma. Composed mostly of hyaline cartilage, they
are smooth, firm, submucosal round or nodular masses.
Neurogenic tumors are extremely rare but may occur in all age
groups. The two types are schwannomas and neurofibromas.
The larynx is the most common site of localized amyloid
deposition in the respiratory tract. An amyloid is a submucosal
mass of the vocal folds or the vestibular fold. Systemic
involvement should be ruled out.
The larynx is involved in 1% to 5% of patients with sarcoidosis.
The epiglottis is the most common site of laryngeal
involvement.
CHAPTER REFERENCES
1. Nasri S, Sercarz JA, McAlpin T, et al. Treatment of vocal fold granuloma using botulinum toxin
type A. Laryngoscope 1995;105:585588.
2. Mounts P, Kashima H. Association of human papilloma virus subtype and clinical course in
respiratory papillomatosis. Laryngoscope 1984;94:2844.
3. Cohen SR, Geller KA, Seltzer S, et al. Papilloma of the larynx and tracheobronchial tree in
children: a retrospective study. Ann Otol Rhinol Laryngologol 1980;89:497503.
4. Shah K, Kashima H. Rarity of cesarean delivery in cases of juvenile onset respiratory
papillomatosis. Obstet Gynecol 1986;68:795799.
5. Quick CA, Foucar E, Dehner LP. Frequency and significance of epithelial atypia in laryngeal
papillomatosis. Laryngoscope 1979;89:550560.
6. Haglund S, Lundquist PG, Cantell K, et al. Interferon treatment in juvenile laryngeal
papillomatosis. Arch Otolaryngol 1981;107:327332.
7. Shikowitz MJ, Abramson AL, Freeman K, et al. Efficacy of DHE photodynamic therapy for
respiratory papillomatosis: immediate and long-term results. Laryngoscope 1998;108:962967.
8. Pransky SM, Magit AE, Kearns DB, et al. Intralesional cidofovir for recurrent respiratory
papillomatosis in children. Arch Otolaryngol Head Neck Surg 1999;125:11431148.
9. Rosen CA, Woodson GE, Thompson JW, et al. Preliminary results of the use of indole-3-carbinol
for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg 1998;118:810815.
10. Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: a
classification based on endothelial characteristics. Plast Reconstr Surg 1982;69:412422.
11. Sie KC, McGill T, Healy GB. Subglottic hemangioma: ten years' experience with the carbon
dioxide laser. Ann Otol Rhinol Laryngol 1994;103:167172.
12. Dixon JA, Davis RK, Gilbertson JJ. Laser photocoagulation of hemangiomas of the head and
neck. Laryngoscope 1986;96:537541.
13. Rebeiz EE, April M, Bohigian RK, et al. Nd:YAG laser treatment of vascular malformation of the
head and neck: an update. Otolaryngol Head Neck Surg 1991;105:655661.
14. Yellin SA, LaBruna A, Anand VK. Nd:YAG laser treatment for laryngeal and hypopharyngeal
hemangiomas: a new technique. Ann Otol Rhinol Laryngol 1996;105:510515.
15. Werner JA, Lippert BM, Gottschlich S, et al. Ultrasound-guided interstitial Nd:YAG laser
treatment of voluminous hemangiomas and vascular malformations in 92 patients. Laryngoscope
1998;108:463470.
16. Liekens S, Andrei G, Vandeputte M, et al. Potent inhibition of hemangioma formation in rats by
the acyclic nucleoside phosphonate analogue cidofovir. Cancer Res 1998;58:25622567.
17. Lack E, Worsham G, Callihan M, et al. Granular cell tumor: a clinicopathologic study of 110
patients. J Surg Oncol 1980;13:301316.
18. Devaney KO, Ferlito A, Silver CE, et al. Cartilaginous tumors of the larynx. Ann Otol Rhinol
Laryngol 1995;104:251255.
19. Schaeffer BT, Som PM, Biller HF, et al. Schwannomas of the larynx: review and computed
tomographic scan analysis. Head Neck Surg 1986;8:469472.
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11 cases. Mod Pathol 2000;13:528535.
21. Mitrani M, Biller HF. Laryngeal amyloidosis. Laryngoscope 1985;95:13461347.
22. Benjamin B, Dalton C, Croxson G. Laryngoscopic diagnosis of laryngeal sarcoid. Ann Otol Rhinol
Laryngology 1995;104:529531.
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of an instrument. Arch Otolaryngol 1970;91:196199.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

54 VOICE DISORDERS AND PHONOSURGERY
Head & Neck SurgeryOtolaryngology
54




VOICE DISORDERS AND PHONOSURGERY
GERALD S. BERKE

G.S. Berke: Division of OtolaryngologyHead and Neck Surgery, University of CaliforniaLos
Angeles, Los Angeles, California.


Voice Disorders Affecting the Traveling Wave
Vocal Fold Inflammation and Masses
Asymmetric Stiffness Disorders
Symmetric Laryngeal Disorders
Objective Measures of Voice Disorders
Glottography
Imaging
Airflow Measures
Acoustic Measures
Multidimensional Approach to Voice Disorders
Phonosurgery for Voice Disorders
Mucosal Lesions
Vocal Fold Inflammation
Asymmetric Stiffness Disorders
Surgery for Asymmetric Stiffness Disorders
Symmetric Stiffness Disorders
Cricothyroid Subluxation for Voice Enhancement
Complications
Controversies
Chapter References
Although the concept of manipulating laryngeal biomechanics to improve vocal function
is not new, there has been a recent proliferation of surgical techniques to affect laryngeal
function. These include methods that increase the stiffness of the vocal folds, medialize
the vocal folds, alter the pitch by changing the tension of the vocal folds, and augment the
tissues using injection of alloplastic materials. As additional knowledge concerning the
essential elements needed for oscillation is accumulated, it is not inconceivable that in the
future a biologically fabricated neolarynx preserving both respiratory function and
phonation could be offered to selected patients. If these recommendations seem at first
implausible, the reader is reminded that physiologic vibration of the airstream is not
unique to the larynx. Examples can be found from the Bronx cheer to esophageal speech.
Engineering of a neolarynx requires a detailed understanding of the viscoelastic
properties of the human vocal folds. This is currently the subject of ongoing
investigation. Relevant basic science laryngologists, phoneticians, speech therapists, and
vocal pedagogists use a number of terms synonymously to describe the perception of
abnormal voice. These include harshness, hoarseness, roughness, harsh breathy quality,
laryngealized creaky voice, and diplophonia. Although a full understanding of the factors
that characterize abnormal voice are just beginning to emerge, the biomechanics
underlying normal voice production are starting to come together in a more unified way.
A little over 20 years ago, Baer quantitatively described for the first time the wave nature
that had been described by Timcke, von Leden, and Moore based on high-speed film of
the vibrating larynx. Baer's study showed that the vocal fold vibration occurs in both
lateral and vertical planes. Functionally, he defined an upper margin and a lower margin
to the vocal fold. During phonation, air passes through the glottis, producing vocal fold
vibration. The lower margins separate first, and before the upper margins separate, an
elliptical volume of air is formed in the subglottal vault confined by the upper margins
superiorly and the lower margins laterally. As the upper margins move laterally, the puff
of air is released, that is, the glottal puff. The lower margins then return to midline to
effect closure of the glottis; this is followed by the return to the midline of the upper
margins as a new glottic vibratory cycle begins. A delay between the opening of the
lower and upper margins of the vocal fold occurs and is referred to as phase delay.
Viewed on high-speed film or by stroboscopy, this fluidlike horizontal and vertical
movement of the vibrating vocal folds appears as a traveling mucosal wave. This wave
motion is the primary influence on the rise and fall in the amount of air flowing through
the glottis. The modulated airflow emanating from the larynx moves through the vocal
tract, producing a pressure wave that is transmitted through the air and interpreted
perceptually as a voice with a fundamental frequency and associated harmonics of
varying amplitudes. Thus, the traveling wave of the vocal folds affects the sound
produced by the larynx.
What factors are pertinent to the characteristics of the traveling wave? Fujimura proposed
the body-cover theory of vocal fold vibration. It suggests that the layer structure of the
vocal fold divides into two groups that have different rheologic properties. The cover is
composed of squamous epithelium and the superficial and intermediate layers of loose
connective tissue or lamina propria. The cover is pliable but has no intrinsic contractile
properties. The body is made up of the deep layer of lamina propria and the
thyroarytenoid muscle. Cricothyroid muscle contraction produces a stretching of the
cover, and thyroarytenoid muscle contraction produces a stiffening of the body. Thus, the
combined stiffness of the entire vocal fold is determined by the extrinsic longitudinal
tension on the cover and the internal stiffening of the body. Evidence suggests that the
vocal fold's traveling wave motion occurs primarily in the cover. Changes in the stiffness
or tension of the vocal folds may affect the motion of the wave. This is because the
velocity of a wave in an elastic medium, such as the vocal folds, is directly related to the
stiffness of the medium and inversely related to the density of the medium. Thus, as the
stiffness in the vocal folds increases, due to muscular contraction, the traveling wave
velocity also increases and the pitch rises (1).
VOICE DISORDERS AFFECTING THE TRAVELING WAVE
Any laryngeal lesion that can affect traveling wave motion can produce aberrant
modulation of the air flowing through the glottis. These include vocal fold edema, mass
lesions, and asymmetric and symmetric stiffness disorders.
Vocal Fold Inflammation and Masses
Inflammation associated with edema of the vocal folds would restrict the motion of the
traveling wave and thus diminish the ability of the vocal folds to modulate the airflow.
Mass lesions or vocal fold scarring may produce irregular vibration of the vocal folds as a
result of differences in mass between the folds. These lesions have been associated with
the appearance of energy at inharmonic frequencies, such as noise in the source spectrum.
Mass lesions also may affect vibration by preventing the vocal folds from touching. This
results in the escape of unmodulated airflow through the glottis. Furthermore, mass
lesions can alter the viscoelastic characteristics of the vocal folds. For example, patients
with microinvasive carcinoma involving the epithelium and lamina propria often exhibit
loss of traveling wave motion because of the increased stiffness imparted by the cellular
density of the neoplasia.
Asymmetric Stiffness Disorders
Asymmetric stiffness occurs in vocal fold paresis/paralysis states. Stroboscopic
examination of patients with asymmetric stiffnesses usually shows changes in the
amplitude or velocity of the traveling wave. These amplitude/velocity changes are
significant because the more forceful the vocal cords close during vibration, the more
energy is imparted to the higher frequencies with the result that the voice sounds loud and
bright. Conversely, in paresis/paralysis states, because the vocal folds close more slowly
and with less force, less energy is imparted to the higher harmonics, and the voice sounds
soft or breathy. Furthermore, because asymmetric stiffnesses are often associated with
large leaks of unmodulated airflow, the perception of breathiness is commonly associated
with a perception of hoarseness because of the white noise produced by the unmodulated
leaky air.
Typically, entrainment (simultaneous opening and closing of the left and right vocal
folds) occurs through tissue proximity and airflow. However, when wide glottal gaps are
associated with asymmetric stiffness, the left and right traveling wave velocities may
diverge as a result of a loss of entrainment. When this occurs, both vocal cords may
actually vibrate at different frequencies, resulting in the acoustic perception of
diplophonia (phonation with two simultaneous fundamental frequencies). Subharmonic
frequencies (below the fundamental frequency) also may be generated. Both diplophonia
and subharmonic frequencies often sound harsh to the listener.
Symmetric Laryngeal Disorders
In contrast to asymmetric laryngeal states, another group of patients show symmetric
hyperfunctional or hypofunctional voice disorders. An example is spasmodic dysphonia,
which is a symmetric hyperfunctional disorder in which the normal neuromuscular reflex
loops controlling intralaryngeal medial adductory compression are disturbed, resulting in
a mismatch between the glottal resistance, which must be overcome to initiate phonation,
and the pulmonary driving pressure. When this occurs, it is difficult to sustain uniform
vibration because the glottal resistance is too high for the pulmonary pressure that is
generated. Hyperfunctional voice disorders often sound harsh with a strained quality.
Another group of patients may demonstrate symmetric weakened closure. For example,
elderly patients frequently lose muscular tone in the thyroarytenoid muscle; this results in
vocal fold bowing or the appearance of a sulcus in the mucosal cover. These forms of
glottal insufficiency produce soft and harsh voices.
OBJECTIVE MEASURES OF VOICE DISORDERS
Objective measurement systems have been developed to permit evaluation of laryngeal
function for the purposes of documentation and quantification. This is important because
untrained listeners often judge the same patient's degree of hoarseness differently. The
most frequently used objective measures are glottographic, stroboscopic imaging,
aerodynamic, and acoustic.
Glottography
Glottography uses physiologic sensors to record the amount of light transilluminated by
the larynx during vibration, termed photoglottography (PGG), or the degree of vocal fold
contact, termed electroglottography (EGG). EGG and PGG signals are complementary in
that PGG measures the degree of vocal fold opening and EGG measures the degree of
vocal fold closure. Changes in glottographic waveforms have been observed to reflect
changes in laryngeal vibration associated with mass lesions or asymmetric stiffness
states. Three measures that provide information about glottal vibration are open quotient,
speed quotient, and shift quotient. Open quotient is the duration that the folds are open
over the length of the glottic cycle. Speed quotient is the duration of glottal opening over
the duration of glottal closing. Shift quotient is the time that peak opening occurs in
relation to the duration of glottal opening. Glottography is a noninvasive test, and the
analyses of the signals can be automated through computed programs. Unfortunately, the
output is the sum total of the vibration of both the left and right vocal cords. Thus, the
precise nature of an anatomic lesion cannot be discerned based on EGG and PGG signals
alone.
Imaging
Cinelaryngoscopy or videolaryngoscopy has proved to be helpful in documenting and
clarifying a variety of laryngeal lesions. Indirect laryngoscopy examines only the static
position and gross adductory/abductory movements of the vocal cords. In contrast,
laryngeal stroboscopy can be used to examine the detailed vibratory nature of the vocal
folds during phonation. The principles of stroboscopy have been known since about
1930, and Oertel was the first to apply stroboscopy to the study of the larynx (2). Modern
laryngostroboscopes use flashes of light to create a montage of the vibrating folds. The
pitch of phonation or a frequency generator are used to control the strobe flashes to create
the impression that the vocal folds are vibrating in slow motion. Stroboscopy has been
shown to be useful in the diagnosis of phonatory disorders and the early detection of
invasive glottic cancer. Because stroboscopy samples images throughout many vibratory
cycles, very irregular vibratory modes cannot be accurately represented. However, quasi-
stable vibratory patterns that occur in vocal fold paralysis can usually be adequately
evaluated stroboscopically. With the advent of personal computed analysis of digitalized
images, subjective evaluation of stroboscopic images will be replaced by quantitative
evaluation in the future (3).
Airflow Measures
Aerodynamic instrumentation can be used to measure the airflow through the glottis and
the pressure beneath the glottis. The quotient of estimated subglottic pressure and mean
translaryngeal airflow can be used to calculate glottal resistance. Patients with paralysis
usually demonstrate low glottal resistance. Patients with hoarseness and lesions produced
by increased vocal fold stiffness usually present with elevated glottal resistance. Another
measure, the ratio of the acoustic power to the subglottic power or vocal efficiency also
can be calculated and may be useful in specifying a variety of laryngeal problems. A
sophisticated aerodynamic technique uses a special type of acoustic filter (inverse filter)
to remove the effects of the vocal tract on the airflow pulse, permitting evaluation of the
glottal flow waveform shape. This measure is useful because the acoustics of phonation
are determined in great part by the shape of the airflow pulse emanating from the larynx.
For example, patients with breathy voices exhibit more sinusoidal-appearing flow
waveforms than patients with normal voices. Sinusoidal-appearing flow waveforms
typically occur when the vocal folds close more slowly and with less force as a result of
paresis or paralysis states. In contrast, flow waveform rise and fall times are more abrupt
in persons with normal voices because of forceful and rapid vocal fold closure.
Aerodynamic measures are noninvasive, but because they are far field measurements,
they seldom indicate the exact nature of the laryngeal disorder.
Acoustic Measures
Acoustic measures are useful in that they have the potential to quantitate the degree of
vocal roughness. Patients with harsh voices demonstrate higher perturbation than normal
in the peak-to-peak timing of each glottal pulse. This frequency perturbation has been
termed jitter. Another measure is of the cycle-to-cycle variation in the amplitude of the
pulse and is termed shimmer. Generally, analysis can be made of timing relationships in
the acoustic signal (time domain measures) or amplitude measurements of the
frequencies in the acoustic signal (frequency domain measures). Jitter and shimmer are
both time domain measures. A frequency domain measure F to H1 difference (F0-H1)
compares the amount of energy present in the fundamental frequency (F0) with the
amount of energy present in the first harmonic (H1). Soft, breathy voices tend to have
less energy in the harmonics and more energy in the fundamental frequency and thus
would demonstrate a larger F0-H1 difference. Although trained human ears are probably
as sensitive as any acoustic analysis system, acoustic analyses have the advantage of
being able to provide quantitative documentation of the degree of deviation from
normality.
MULTIDIMENSIONAL APPROACH TO VOICE DISORDERS
Whereas each one of the aforementioned measuresglottographic, imaging,
aerodynamic, and acousticprovides some aspect of a patient's problem, a more
complete picture of vocal function can be obtained by taking into consideration a number
of objective measures on the same patient. An example of this is illustrated for patient
B.M., who presented after a cervical fusion with a complaint of a very weak, harsh voice.
Indirect laryngoscopic examination demonstrated that both cords were mobile and
appeared grossly normal. Table 54.1 demonstrates phonatory instrumental values
obtained for this patient. The normal 95% confidence interval for the measures is also
shown for comparison. Of note is that the patient's acoustic measures in both the time
domain (jitter, shimmer) and frequency domain (number of harmonics, F0-H1) are
abnormal, indicating that the problem is producing an irregular and diminished
modulation of the airstream. B.M.'s glottographic measures (speed quotient, shift
quotient) indicate that the vibrations of the vocal folds are asymmetric. Furthermore,
B.M.'s aerodynamic evaluation shows that the voice is weak because of low glottal
resistance.

TABLE 54.1. VOICE MEASURES IN
ILLUSTRATIVE PATIENT



Figure 54.1 shows videostroboscopic images taken from the most open and most closed
portions of B.M.'s videostroboscopy, respectively. The images have been digitalized and
stored in a computer to allow for objective measurement using image processing
software. The most-closed to most-open area ratio is 989 pixels to 8,131 pixels, or 12%,
indicating that vocal fold closure is within normal limits. In contrast, the area pixel ratio
would be greater than 20% in patients with poor glottal closure. Furthermore, a symmetry
ratio comparing right with left vocal fold excursion can be measured from the digitalized
images. For patient B.M., the excursion of the right vocal fold is calculated as a minus c
in Fig. 55-1A and Fig. 55-1B. The right vocal fold excursion is 8.7 pixels. Similarly, the
excursion of the left vocal fold is 1.2 pixels (b minus d). The symmetry ratio is (1.2/8.7)
= 0.14, indicating that the left vocal fold moves only 14% of the right vocal fold during
the cycle. The discrepancy in the left and right vocal fold excursion is related to less
vocal fold stiffness on the left side and its resulting affect on slowing the traveling wave
motion. Considered together, these acoustic, glottographic, aerodynamic, and imaging
measures indicate that B.M. is suffering from an asymmetric stiffness disorder due to a
weakening of his left vocal fold from injury to his laryngeal nerve during his cervical
fusion.

FIGURE 54.1. Videostroboscopic images from the most
open (A) and most closed (B) portions of a vibratory
cycle.



Multidimensional evaluation can also be useful in comparing the effects of different
treatment strategies on laryngeal function.
PHONOSURGERY FOR VOICE DISORDERS
Phonosurgery is designed to alter phonation and has seen increasing interest by
practitioners within recent years. However, some have suggested that it may be
phonyjust surgery masquerading as new and advantageous surgical methods.
The truth is that surgery on the vocal apparatus when successfully accomplished can have
a positive impact on a person's self-image, social interaction, and job performance. To
accomplish this, a few major tenets have to be carefully considered. Computerized
modeling for the most part has emphasized two parameters that are essential to normal
vocal fold vibration and voicing. These are the glottal gap and normal symmetric vocal
fold stiffness. The functional characteristics of normal phonatory posture are (a) posterior
commissure closure, (b) symmetric thyroarytenoid stiffness, and (c) equal vertical
position (Table 54.2).

TABLE 54.2. FUNCTIONAL CHARACTERISTICS
OF NORMAL PHONATORY POSTURE



For example, one can closely simulate on the computer the effects of recurrent laryngeal
nerve paralysis on glottal vibration by just increasing the glottal gap while decreasing the
stiffness of the lower margin in one vocal fold. During phonation, the interarytenoids and
lateral cricoarytenoid muscles contract to provide forceful closure and apposition of the
vocal folds. This has a net effect of forcing the airstream to flow between the vocal folds,
thus exciting vibration. Without closure, the airstream exits the glottis unmodulated, and
very little of the subglottic air power is converted into sound energy.
One might then ask, if the lateral cricoarytenoid and interarytenoid muscles control
glottal closure, what is the role of the thyroarytenoid muscle and cricothyroid muscle?
Once the vocal folds are in apposition, the thyroarytenoid muscles (originating at the
vocal processes and inserting into the anterior commissure of the thyroid cartilage) have a
profound effect on vibration. The thyroarytenoid muscle controls the stiffness of the
vocal fold and, in so doing, the vocal pitch (along with the cricothyroid muscle) and
glottic resistance (primary factor influencing vocal intensity). The cricothyroid muscle is
the antagonist to the action of the thyroarytenoid muscle. Although thyroarytenoid
muscular activity would be expected to decrease or shorten the vocal folds, creating a
thicker fold with more contact area, cricothyroid activity would have a tendency to thin
and lengthen the vocal fold with less of an area of contact.
Cricothyroid muscular contraction actively raises the pitch by increasing vocal fold
tension while decreasing the effective vibratory mass per unit area. Furthermore,
cricothyroid activity has less of an effect on glottic resistance than the thyroarytenoid
(Fig. 54.2). Surprisingly, although the laryngeal muscles control laryngeal stiffness, the
actual vibration (tissue wave) occurs in the loose connective tissue layer of the lamina
propria. Without the lamina propria, there would be no traveling wave and no modulation
of the airstream. Understanding the biomechanics of the larynx is important because, to
determine which phonosurgical procedure is most appropriate for a given patient, the
laryngologist must first have a good idea of which factors are adversely affected. The
laryngologist has to determine whether a patient's voice disorder is related to lesions
affecting the vocal fold mucosa, vocal fold stiffness, or vocal fold closure. Frequently,
more than one of these may be affected at the same time. Often a multidimensional
analysis of voice is required. For example, patients with vocal fold paresis or paralysis
usually demonstrate problems with glottic closure and asymmetric stiffness. Patients with
excessively forceful closure or hyperadduction states also may exhibit vocal process
contact ulcers or granulomas. Surgical, medical, and behavioral intervention should be
aimed at reversing abnormalities observed in closure, stiffness, and mucosal lesions.

FIGURE 54.2. Cutaway posterior view of larynx
depicting intralaryngeal course of the recurrent laryngeal
nerve, muscular process of arytenoid with posterior
cricoarytenoid muscle (controlling dilation), lateral
cricoarytenoid and interarytenoid muscles (controlling
vocal fold closure), and vocalis/cricothyroid muscle
(controlling vocal fold stiffness).



The decision to use a particular surgical intervention should be guided by a number of
factors; foremost is the experience of the laryngologist in using a particular technique.
Other important considerations include whether the patient exhibits a paresis or paralysis,
the patient's age and physical status, and to what degree normal voicing is required.
MUCOSAL LESIONS
Masses in the form of leukoplakia, carcinoma, nodules, polyps, or contact ulcers and
granulomas are easily diagnosed visually. Mass lesions are frequently successfully
treated by just getting patients to stop the inciting factor, tempered with a small amount
of patience on the part of the physician and the patient. Surgery should be reserved for
lesions resistant to conservative therapy or the slightest suspicion of carcinoma. Laser
surgery should be reserved for patients with mass lesions that have a propensity to bleed
easily (such as papillomas) and patients in whom a large amount of tissue needs to be
removed (such as with severely dysplastic pachylaryngis). Laser surgery of small vocal
fold lesions is frequently complicated by inadvertent injury to the normal surrounding
lamina propria and secondary protracted healing time with hoarseness. Surgical therapy
of small vocal fold masses is best handled with a cold knife or laryngeal scissors. I have
found that optimum results are achieved when, after removal of the lesion, the edge of the
vocal fold is as straight as possible and the lamina propria is left intact.
Benign vocal fold masses usually are the result of multiple factors acting concomitantly.
For example, granulomas frequently are associated with constant throat clearing and
posterior commissure inflammation from gastroesophageal reflux disease. Similarly,
vocal nodules occur in patients who have voice abuse and chronic laryngeal
inflammation, often due to smoking. Surgical removal of these masses has proved to be
of little benefit if the underlying etiologies are not corrected. Patients with granulomas
and contact ulcers are now most effectively treated with botulinum toxin injections to put
the vocal fold at rest and allow the granuloma/ulcer to heal. Usually a paralyzing dose, 12
U, is given to the side of the lesion and a smaller dose, 3 to 5 U, is given to the
contralateral side to prevent overcompensation during the healing phase. I have found
this technique to be of greatest use in the treatment of granulomas, but good results also
have been achieved for patients with polyps and nodules.
Defects in the vocal fold medial edge produce hoarse voices, as does loss of the loose
connective tissue that is necessary for vibration. Vocal fold mucosal defects and scarring
are usually the result of trauma, frequently iatrogenic. A variety of treatments are
available, none of which is entirely successful. Polytef injection near the free edge of the
vocal fold is contraindicated because of migration and granuloma formation. Recently,
cross-linked collagen and autogenous fat injections have been used. Both have
advantages and disadvantages. Collagen is expensive, and its long-term presence is
controversial. It is not known whether collagen has similar viscoelastic attributes to loose
connective tissue. One advantage is that it can be injected with a small 25-gauge needle,
so that precise placement is possible. New products for augmentation are now on the
market. These include injection of autogenous collagen harvested from a small 2-inch-
square piece of skin and synthesized collagen. In the near future, it may be possible for
laboratories to grow lamina propria, which would be an ideal agent to replace the loose
connective tissue of the vocal fold. Fat can be liposuctioned using an 18-gauge needle
and a 10-mL syringe. A Teflon (3-M Corporation) injector can then be used to augment
defects. Long-term stability is also unknown, and precise placement is difficult. Patients
who undergo removal of bilateral vocal fold anterior masses may end up with webbing of
the anterior commissure, resulting in abnormal acoustics. This complication may be
avoided by not permitting raw vocal fold mucosa to come into contact for extended
periods of time and to heal with a synechia. Removal of bilateral anterior masses may
need to be staged.
VOCAL FOLD INFLAMMATION
Patients with laryngeal inflammation usually exhibit swollen injected vocal folds and
erythema of the surrounding mucous membranes. Not infrequently, one of the cords may
show frank hemorrhage into it. A variety of etiologies can produce similar inflammatory
appearances, and patients may have more than one cause producing the irritation. The
physician needs to be cognizant of vocal abuse, smoking, and common and rare
pathogens. An important factor is reflux laryngitis/esophagitis and its associated constant
throat clearing and hypopharyngeal and gastric acidity. The mainstay of therapy for
inflammatory lesions involves eliminating the inciting agent. The maintenance of proper
hydration and avoidance of chronic mouth breathing during sleep are important factors.
In selected patients, a short course of systemic steroids can often be useful. Aerosolized
steroid sprays, although effective in reducing vocal fold inflammation, should not be used
because of the infrequent but serious complication of developing oral and
hypopharyngeal fungal superinfections. Seldom is surgery indicated unless biopsy for
culture or for ruling out neoplasia is unavoidable.
ASYMMETRIC STIFFNESS DISORDERS
Asymmetric stiffness disorders include a variety of paralysis and paresis lesions. Gross
indirect laryngoscopic examination of the hypopharynx may appear entirely normal so
that dynamic functioning during phonation may be the only clues available in making the
correct diagnosis. Patients almost never demonstrate the classic paramedian or
intermediate vocal fold positions associated with recurrent laryngeal or combined
recurrent and superior laryngeal nerve paralysis, respectively. Instead, a broad diversity
exists in which patients exhibit varying degrees of paresis/paralysis involving either the
recurrent or superior laryngeal nerves and a spectrum of vocal fold closure and stiffness
(Table 54.3). In addition, with time, atrophy and fibrosis of the affected vocal fold ensue,
and compensatory laryngeal postures mask many of the more classic descriptions.
Because of these difficulties, a number of laryngologists have begun to classify laryngeal
asymmetric stiffness disorders functionally rather than anatomically. This requires a
multidimensional analysis of vocal function. Electromyography has been applied to the
diagnosis of laryngeal neuromuscular disorders. However, electromyographic evidence
for neuromuscular innervation often does not correlate with clinically observable
laryngeal dysfunction. Not infrequently, modern diagnostic tools fail to provide a
definitive diagnosis, so the laryngologist must fall back on his or her experience. A
patient who presents with a new undiagnosed voice disorder resulting from asymmetric
stiffness of the vocal folds needs a thorough workup to rule out treatable underlying
causes. Patients with asymmetric laryngeal stiffness disorders should be advised to
undergo voice therapy to maximize their vocal function; they may be candidates for a
variety of surgical interventions to improve their voice.

TABLE 54.3. PATTERNS OF GLOTTAL
INSUFFICIENCY



Surgery for Asymmetric Stiffness Disorders
Teflon Injection
Vocal fold augmentation by Teflon injection has been widely viewed as improving voices
and reducing aspirations since its introduction in 1962. High-speed cinematography
shows improved vibration and medial placement of the paralyzed cord after injection, and
acoustic analyses and laryngeal function studies also show improvements after injection.
The following protocol is my technique, which has been modified from the methods of
Arnold, Lewy, and Hirano. After intubation and suspension microlaryngoscopy, the
Bruening syringe is introduced until the needle tip pushes the ipsilateral ventricular fold
as far laterally as possible. Pointing the needle in an oblique direction, the surgeon
advances the needle through the floor of Morgagni's ventricle to a depth of 3 mm (to the
hub of the injector needle) in the space between the thyroarytenoid muscle and the
thyroid cartilage. The target in the anteroposterior dimension is usually a point one fourth
of the distance along an imaginary mid-sagittal line extending from the tips of the vocal
processes to the anterior commissure as depicted (Fig. 54.3). Teflon is injected in 1-mL
aliquots until the vocal cord approximates the mid-sagittal line.

FIGURE 54.3. Target for Teflon injection.



There is no doubt that Teflon augmentation will continue to be the primary method for
correcting glottal insufficiency. However, a number of concerns regarding Teflon
injection have arisen. Proponents admit Teflon fails to improve voice quality in at least
10% of cases, and the long-term failure rate is unknown. The degree of improvement
following injection is apparently affected by the amount and position of injection. Teflon-
injected vocal cords in humans may lack a mucosal wave, thus interfering with a normal-
sounding voice. Injection close to the free margin of the cord increases its stiffness and
alters its vibratory characteristics. Other complications of this procedure include
granuloma formation, migration of the Teflon, imprecise placement, and overinjection
with possible airway obstruction.
Thyroplasty
As an alternative to Teflon injection, a number of surgeons have begun to treat
asymmetric stiffness states by laryngeal framework surgery or thyroplasty (Fig. 54.4).
Isshiki and colleagues categorized four types of thyroplastic surgeries. Type 1 provides
lateral compression to the paralyzed cord, narrowing the glottic chink; type 2 creates a
lateral expansion of the glottis; type 3 shortens and relaxes the cords bilaterally; and type
4 lengthens and stretches the cords. Based on a comparison of these surgeries in treating
unilateral vocal fold paralysis in canines, Isshiki recommends using type 1 thyroplasty for
unilateral recurrent paralysis, and type 1 and type 4 together for combined unilateral
superior and recurrent laryngeal nerve paralysis. In this study, the degree of voice
improvement was evaluated subjectively as improved or rough, and the mechanical effect
of the larynx was studied only with laryngoscopy.

FIGURE 54.4. Isshiki has outlined four types of
laryngeal framework surgery.



Subsequent studies have reported good results using thyroplasty to treat unilateral
paralysis in humans. Advantages of thyroplasty over Teflon injection also have been
reported (4); however, objective evidence supporting clinicians' claims is lacking. The
procedure for thyroplasty type 1 has been well described in the literature by Isshiki. The
procedure involves cutting a window in the thyroid cartilage, which is then pushed
medially and held in place with a Silastic wedge. Cartilage window dimensions usually
fall within the following rectangle (Fig. 54.5): (a) upper rectangle side, half the distance
from the anterior thyroid notch to the insertion of the cricothyroid muscle; (b) lower
rectangle side, half the distance from the superior rectangle line to the insertion of the
cricothyroid muscle; (c) posterior rectangle side, one third to one half the distance from
the midline of the thyroid cartilage to the insertion of the inferior constrictor muscle; and
(d) anterior rectangle side, within 5 to 7 mm lateral to the midline of the thyroid cartilage.

FIGURE 54.5. Positioning of the window on thyroid
cartilage in Isshiki type 1 thyroplasty.



Silastic wedges usually fall within the following dimensions: 4 to 6 mm high, 8 to 12 mm
wide, anterior depth 2 to 3 mm, and posterior depth 4 to 5 mm. My technique is similar to
Isshiki's, except that a three-sided anteriorly hinged rectangular cartilage window is used
(Fig. 54.6). The upper and lower rectangular sides run from the anterior midline of the
thyroid cartilage to approximately half the distance from the posterior border of the
thyroid lamina. After carefully elevating the inner perichondrium, the cartilage window,
which is hinged anteriorly, is then pushed medially and held in place using either a
Silastic wedge or an additional piece of cartilage harvested from the superior border of
the thyroid cartilage. The harvested cartilage is placed under the posterior edge of the
window to medialize the hinged thyroid lamina.

FIGURE 54.6. Author's technique for medialization
laryngoplasty.



The advantage of the author's technique is that it ensures a straight edge to the medialized
vocal fold from the anterior commissure to the vocal process (5). The main disadvantage
of all medialization laryngoplasty procedures is that posteriorly the thyroid lamina cannot
medialize the vocal process. This is because anatomically the thyroid cartilage window
hits up against the signet ring of the cricoid cartilage. This means that patients with large
posterior glottic chinks continue to demonstrate low glottal resistance and less than
normal vocal efficiency levels. Medialization laryngoplasty can be reversed, but not
without considerable difficulty. Complications of type 1 thyroplasty include extrusion of
Silastic wedges into the laryngeal lumen, persistent inflammation of the vocal fold, and
anterior chinks in the vocal fold mucosa due to an improperly placed Silastic wedge.
Adduction of the arytenoid cartilage also has been used to reduce glottal incompetence.
Isshiki performed an arytenoid adduction on five patients with a large glottal chink. In
this procedure, a suture was placed around the muscular process of the arytenoid through
the anterior thyroid cartilage and tied with enough tension to adduct the arytenoid to the
midline. Postoperatively, all five patients had improved voices as demonstrated on
spectrograms. Although this procedure has been performed for many years, it has seldom
been used to treat asymmetric stiffness disorders, and very little has been published
regarding its usefulness. An advantage of Isshiki's technique over other methods that pin
the arytenoid cartilage is that it reproduces the biomechanical effect of lateral
cricoarytenoid muscular contraction. Thus, the problem of interpatient anatomic
variability is minimized because the arytenoid is adducted to its normal position in each
patient.
In performing an arytenoid adduction, the thyroid cartilage is first exposed down to the
posterior margin. The constrictor muscles are elevated and sectioned off. Dissection
proceeds on the inner surface of the thyroid cartilage. The mucosa of the piriform recess
is reflected laterally, and the muscular process of the arytenoid cartilage is then
identified. The muscular process is palpated as a movable knuckle to which the
cricoarytenoid muscles are attached. A 4-0 proline suture is placed around the muscular
process of the arytenoid and then passed just deep to the thyroid ala, brought out
anteriorly, and tied over a bolster. I have found that a two-hole microplate serves as a
good bolster over which to secure the suture (Fig. 54.7). It has been our experience that a
4-0 proline suture ties with approximately the correct amount of force before breaking.
The suture should be brought out through the thyroid cartilage within the following
perimeter: (a) superior perimeter, three fourths of the distance from the thyroid notch to
the insertion of the cricothyroid muscle; (b) inferior perimeter, insertion of the
cricothyroid muscle; (c) anterior perimeter, one third of the distance from the midline of
the thyroid cartilage to the insertion of the inferior constrictor muscle; and (d) posterior
perimeter, two thirds of the distance from the midline of the thyroid cartilage to the
insertion of the inferior constrictor muscle.

FIGURE 54.7. Author's technique for arytenoid
adduction.



Although Isshiki reports performing arytenoid adduction using local anesthesia, I prefer
to use general anesthesia with a small microlaryngoscopy endotracheal tube. After the
stitch is brought out through the thyroid cartilage and before it is tied over the bolster,
direct laryngoscopy is used to verify correct suture placement and adduction of the vocal
process on anterior traction of the suture. It has not been found necessary to disarticulate
the cricothyroid joint to identify the muscular process of the arytenoid cartilage. Because
of significant laryngeal manipulation, arytenoid adduction is best suited for young
patients with long-standing paralysis who exhibit poor closure and wide glottal gaps.
Complications of arytenoid adduction include laryngospasm requiring tracheostomy and
inadvertent entrance into the laryngeal lumen during dissection of the piriform sinus.
Patients who undergo successful arytenoid adduction continue to demonstrate small
asymmetries in vocal fold vibratory excursion during phonation; this is related to lack of
thyroarytenoid muscular innervation. However, perceptually the postadduction voice
sounds normal with normal vocal efficiency measures (6). Table 54.4 and Table 54.5
summarize the effects of the various procedures for asymmetric stiffness disorders.

TABLE 54.4. TREATMENT ASYMMETRIC
STIFFNESS DISORDERS



TABLE 54.5. COMPARATIVE EFFECTS OF
TREATMENT



Combination Techniques
Investigators recently described combinations of procedures to treat glottal insufficiency
(Fig. 54.8). Isshiki proposed adduction and type 1 thyroplasty (7). Tucker described a
technique combining his nerve muscle pedicle reinnervation with type 1 thyroplasty
medialization. In my opinion, the most logical combination would include an arytenoid
adduction combined with an ansa cervicalis to distal recurrent laryngeal nerve
reinnervation. This would have the advantage of simulating lateral cricoarytenoid and
interarytenoid muscular contraction for forceful apposition while at the same time
reinnervating the vocalis muscle to provide additional stiffness to the vocal fold. (For
additional information on thyroplasty, the reader is referred to procedures described by
Richard Stasney and Charles Ford in the Atlas of Head and Neck Surgery-
Otolaryngology.)

FIGURE 54.8. Combination procedures to correct
asymmetric stiffness disorders. A: Adduction plus type 1
thyroplasty. B: Type 1 thyroplasty plus nerve muscle
pedicle reinnervation. C: Arytenoid adduction plus ansa
cervicalis to recurrent laryngeal nerve (RLN)
reinnervation.



SYMMETRIC STIFFNESS DISORDERS
In contrast to asymmetric stiffness disorders in which one side predominates, some
patients exhibit symmetric hypo- or hyperfunctional states. Not infrequently, this group
of disorders is associated with neurologic lesions such as myasthenia gravis or Shy-
Drager syndrome, Parkinson disease, or multiple sclerosis. Vocal tremor usually has
accompanying bulbar and pyramidal tremors. Spastic dysphonia is said to be a focal
dystonia but frequently shows other cranial nerve spasms. Presbylarynges resulting from
a bowing or sulcus vocalis of the vocal folds can produce a harsh, breathy voice.
Muscular tension dysphonia is a disorder resulting from disproportionate and
uncoordinated contraction of the laryngeal abductors and adductors during phonation.
Patients with this problem may show incomplete closure of the vocal processes, whereas
the vocalis muscle appears to be contracting excessively. A dysphonia termed mutational
voice disorder is a condition in which a person has unusually high or low vocal pitch.
Investigators have reported correcting mutational voice disorders with type 3 and type 4
thyroplasties. Other investigators have reported correction of mutational voice disorders
within 5 to 10 minutes using only biofeedback. My experience is that thyroplasty can be
used to alter pitch, but only to a limited degree because of postoperative vocal fold stress
relaxation and strain creep.
Until recently there has been no long-term effective therapy for presbylarynges or
muscular tension dysphonia, other than vocal rehabilitation. I recently found that
percutaneous injection of collagen can significantly improve the vocal function of these
patients. This is usually performed under videofiberscopic guidance using a lidocaine
spray to anesthetize the nose and a small 27-gauge needle to inject the collagen directly
into the vocal fold via either the transcartilaginous technique or transcricothyroid
membrane injection (8). Collagen usually persists for 1 to 3 months, but can be repeated
several times, and permanent augmentation usually occurs after two or three injections.
Recent reports in the literature indicate that autogenous collagen injection may last
considerably longer.
There is no long-term effective therapy for presbylarynges or muscular tension dysphonia
other than vocal rehabilitation. Finally, it should be remembered that almost anyone can
simulate an abnormal vocal condition. Therefore, it is difficult to separate imitation from
real pathology. Considerable work still needs to be done in this area.
Cricothyroid Subluxation for Voice Enhancement
As laryngoplastic phonosurgery has moved to the forefront as the dominant treatment for
paralytic dysphonia, limitations of dynamic range and vocal flexibility have been
observed. A new procedure, cricothyroid subluxation, has been proposed to enhance
vocal quality after repositioning of the vocal fold edge. Cricothyroid subluxation
increases the distance between the cricoarytenoid joint and the insertion of the anterior
commissure ligament. Zeitels has reported successful outcomes in a small series of
patients in whom he describes increasing the length and the viscoelastic tension in the
denervated vocal fold (9).
COMPLICATIONS
A recent survey of 7,364 otolaryngologists (2,436 responses) indicated that 43% of
otolaryngologists perform medialization laryngoplasty (ML) or arytenoid reduction (AR)
procedures (10). The survey describes 14,621 cases of ML, with the average respondent
performing 12 of these procedures in the past 5 years. The most common major
complications were implant migration and failure to improve voice quality. The implant
extrusion rate was 1%, with most of the extrusions into the airway. The complication rate
was significantly higher among those surgeons who perform fewer than 2 MLs per year
and among surgeons who had performed fewer than a total of 10 MLs.
CONTROVERSIES
Because laryngology is a rapidly advancing field, a number of issues are unsettled. These
span the spectrum from basic research to clinical patient care. For example, a basic
dilemma is why the vocal folds sustain vibration. After all, there is no reason to expect
that the system would oscillate. Two schools of thought have emerged addressing this
question: the myoelastic aerodynamic theory and the collapsible tube theory. van den
Berg's myoelastic aerodynamic theory basically states that vibration occurs through the
reciprocal interplay of the myoelastic forces tending to produce glottal closure and the
aerodynamic forces producing vocal fold opening (11). Collapsible tube theorists believe
that instability (vibration) occurs when the velocity of the transported medium (airflow)
exceeds the tissue wave velocity of the collapsible tube (vocal fold). When this occurs,
the system is constantly collapsing on itself and then resetting, the net effect of which is
oscillation.
Another topic that is clinically relevant involves reinnervation of the larynx for both
respiratory abductor (posterior cricoarytenoid) and phonatory adductor (lateral
cricoarytenoid and thyroarytenoid) function. Reinnervation procedures are abundant in
the literature. Regarding abductory movements, some investigators have tried to
reinnervate the posterior cricoarytenoid muscle with nerve-muscle pedicles or electrically
paced nerve-muscle pedicles. Others have tried selective reinnervation with the phrenic
nerve, external branch of the superior laryngeal nerve, and even cross posterior division
recurrent laryngeal nerve branches. Unfortunately, most animal studies have used
subjective criteria to evaluate the results, and most human studies are anecdotal.
Similarly, a number of techniques for reinnervating the adductory phonatory function
have been described. The simplest involves reanastomosis of an inadvertently divided
recurrent laryngeal nerve. However, unless the reanastomosis is created distal to the
intralaryngeal division of the recurrent laryngeal nerve into its anterior and posterior
divisions, laryngeal synkinesis and lack of physiologic motion ensue. Phonatory
adductive function using nonspecific nerves such as the ansa cervicalis have been
described with good functional results. However, physiologic motion resulting from ansa
cervicalis to recurrent laryngeal nerve anastomoses has not been reported. Nerve-muscle
pedicles also have been reported to reinnervate the thyroarytenoid and lateral
cricoarytenoid muscles. However, objective evidence with good physiologic function
following surgery is lacking. Although not yet achieved, the ideal result will reproduce
the normal physiologic motion of vocal fold abduction during respiration and adduction
and thyroarytenoid muscular contraction during phonation.
Significant advances and refinements in phonosurgery have been based on important
scientific discoveries and technological improvements. Outcome studies have
documented the voice improvement that surgeons have achieved in the areas of
phonomicrosurgery, laryngeal framework surgery, and the use of implantable materials in
the vocal folds. In a recent state-of-the-art review, Ford (12) emphasized that the
innovative use of the rigid endoscopic telescope and intraoperative videostroboscopy
have enhanced the precision of surgical procedures and that alloplastic injections with
materials such as Teflon have been largely supplanted by bioimplantables such as fat,
collagen, and fascia.

HIGHLIGHTS
Laryngeal vibration occurs through a traveling mucosal tissue
wave, which modulates the airstream, producing voice.
Traveling wave motion is pathologically altered by lesions
involving vocal fold inflammation and masses, asymmetric
stiffness disorders, and symmetric stiffness disorders.
Objective measurement systems include glottographic imaging,
airflow, and acoustic measures that can be multidimensionally
applied to the diagnosis of voice disorders.
The two most important characteristics required for normal
laryngeal vibration are adequate laryngeal closure and
symmetric vocal fold stiffness.
Maintenance of an intact lamina propria is essential for normal
vocal fold vibration.
Patients with asymmetric stiffness disorders demonstrate a
broad diversity of paresis/paralysis states due to progressive
atrophy and fibrosis of the affected fold and the appearance of
compensatory laryngeal postures.
Alloplastic materials, laryngeal framework surgery, and
reinnervation may be used to correct asymmetric stiffness
disorders.
Symmetric stiffness disorders usually occur in neurologically
impaired patients and may either be hypofunctional
(presbylarynges) or hyperfunctional (spasmodic dysphonia).
Controversy surrounds the reinnervation of laryngeal function
for both respiration and phonation.
As knowledge of laryngeal biomechanics is implemented,
newer techniques will emerge, permitting modification of the
individual elements making up laryngeal function and the
possibility of physiologically fabricating a neolarynx.
CHAPTER REFERENCES
1. Berke GS, Gerratt BR. Laryngeal biomechanics 1: an overview of mucosal wave mechanics. J
Voice 1993;7:123128.
2. Berke GS, Moore D, Hantke D, et al. Laryngeal modelling: theoretical, in vitro, in vivo.
Laryngoscope 1987;97:871.
3. Sercarz JA, Berke GS, Ye M, et al. Vibratory characteristics of induced and acquired laryngeal
paralyses. Ann Otolaryngol 1991.
4. Koufman JA. Laryngoplasty for vocal cord medialization: an alternative to Teflon. Laryngoscope
1986;96:726.
5. Bielamowicz S, Berke GS. An improved model of medialization laryngoplasty using a three-sided
thyroplasty window. Laryngoscope 1995;105:13.
6. Bielamowicz S, Berke GS, Gerratt BR. A comparison of type I thyroplasty and arytenoid
adduction. J Voice 1995;9:466472.
7. Isshiki N. Vocal mechanics as the basis for phonosurgery. Laryngoscope 1998;108:17611766.
8. Green DC, Berke GS, Ward PH, et al. Point touch technique of botulinum toxin injection for the
treatment of spastic dysphonia. Ann Otol Rhinol Laryngol 1992;101:883887.
9. Zeitels SM, Hillman RE, Desloge RB, et al. Cricothyroid subluxation: a new innovation for
enhancing the voice with laryngoplastic phonosurgery. Ann Otol Rhinol Laryngol 1999;108:1126
1131.
10. Rosen CA. Complications of phonosurgery: results of a national survey. Laryngoscope
1998;108:16971703.
11. Berke GS, Green DC, Smith MC, et al. Experimental evidence in the in vivo canine for the
collapsible tube model of phonation. J Acoust Soc Am 1991;89:13581363.
12. Ford CN. Advances and refinements in phonosurgery. Laryngoscope 1999;109:18911900.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

55 CONTROVERSIES IN LARYNGOLOGY
Head & Neck SurgeryOtolaryngology
55




CONTROVERSIES IN LARYNGOLOGY
JAMES A. KOUFMAN
MILAN R. AMIN
GREGORY N. POSTMA

J.A. Koufman and G.N. Postma: Center for Voice Disorders, Department of Otolaryngology, Wake
Forest University School of Medicine, Winston-Salem, North Carolina.
M.R. Amin: Department of OtolaryngologyHead and Neck Surgery, Hahnemann University Hospital,
Philadelphia, Pennsylvania.


Controversies in Diagnosis
Telescopic versus Fiberoptic Laryngeal Examination
Stroboscopy
Laryngeal Electromyography
Laryngopharyngeal Reflux
Flexible Endoscopic Evaluation of Swallowing versus Modified Barium Swallow
Surgical Controversies
Vocal Process Granulomas
Treatment of Early Carcinoma of the Vocal Fold
Use of Polytef (Teflon) in Laryngology
Laryngoplastic Phonosurgery
Microlaryngeal Surgery
Lipoinjection
Surgery for Spasmodic Dysphonia
Office-Based Laryngeal Surgery
Chapter References
During the past 25 years, the specialty of laryngology and the voice has experienced a
renaissance, primarily because of advancements in diagnostic and therapeutic technology.
The specialty has evolved rapidly, resulting in a proliferation of transition technologies,
that is, advances that are quickly replaced by superior instruments or methods. The
problem of evaluating new diagnostic technology and treatment methods is confounded
by the lack of accepted standards. There is disparity in methods for voice evaluation and
therapy, surgical treatment, and in reporting the outcome of clinical interventions. The
fragmentation of the specialty is due to its newness, and a consensus has not been reached
in many areas. In this chapter we present our views on some of the important
developments and controversies in the field.
CONTROVERSIES IN DIAGNOSIS
Telescopic versus Fiberoptic Laryngeal Examination
Within the past few decades, instrumentation for laryngeal examination has improved
greatly. Because of its superior optics, the first instrument to be popularized was the rigid
telescope. This was often linked to a videostroboscopic system. The clear magnified
images were an advance over mirror examination for viewing the larynx. Unfortunately,
despite the high-quality images obtained, oral examination techniques do not allow
assessment of laryngeal biomechanics. Laryngeal biomechanics are dramatically altered
when one pulls on the tongue and introduces a telescope. At our voice center, the only
indications for oral telescopic laryngoscopy are for stroboscopy when optimal
magnification is needed and for photography of laryngeal pathology. In our practice, the
telescopic examination method is used in approximately 10% of cases, and then only
after transnasal fiberoptic laryngoscopy (TFL) has been performed.
Although TFL was introduced in the 1970s, it was slow to gain popularity because the
images were inferior to those obtained with rigid telescopes. Fortunately, the optical gap
has been narrowed so that the images obtained by TFL (with or without stroboscopy) are
now comparable with those obtained by telescopic laryngoscopy. Transnasal fiberoptic
laryngoscopy allows assessment of laryngeal biomechanics using a variety of vocal tasks,
across the entire vocal pitch range for singing and speaking, as well as for sustained
phonation and connected speech. Telescopic laryngoscopy is an inferior examination
method for assessing many common movement disorders such as vocal cord paresis and
paralysis, spasmodic dysphonia (SD), tremor, and (functional) muscle tension dysphonia.
Because the images are so impressive, many clinicians continue to rely exclusively on
telescopic laryngoscopy for the evaluation of laryngeal and voice disorder patients. Thus,
they mistakenly focus on abnormalities of the vibrating free edge. Using TFL, the
clinician can gain a better understanding of the biomechanical contributions to the
development of free edge pathology. Most importantly, TFL allows the clinician to
differentiate compensatory from underlying laryngeal behaviors. We conclude that TFL
is superior to telescopic laryngoscopy in the evaluation and diagnosis of most functional
and neuromuscular disorders of the larynx.
Stroboscopy
Videostroboscopy is actually two separate functions: videoendoscopy and stroboscopy.
Whereas videoendoscopy is essential in the diagnosis and documentation of virtually all
laryngeal and voice disorders, stroboscopy is important in a limited number of cases.
Stroboscopy allows the clinician to evaluate the mucosal waves of the vocal folds during
telescopic or fiberoptic laryngoscopy. Stroboscopy is not useful in differentiating
functional from organic voice disorders or in diagnosing most neuromuscular diseases. It
is not useful in evaluating neoplastic lesions that involve the anterior commissure, the
vocal processes, or the posterior larynx.
The principal indications and uses of stroboscopy are (a) to differentiate intracordal cysts
from vocal nodules; (b) to evaluate for vocal fold fibrosis/scarring, that is, adynamic
segments after trauma, surgery, or inflammatory disease; (c) to demonstrate recovery of
vocal fold function after vocal fold surgery or laryngoplastic phonosurgery; (d) to
determine the functional significance of vocal fold vascular lesions; and (e) to evaluate
the thickness of some free edge neoplastic lesions, such as leukoplakia or early
carcinoma. In other words, the uses of stroboscopy are limited. The indications for
stroboscopy are summarized in Table 55.1.

TABLE 55.1. STROBOSCOPY



Another important contemporary controversy is the question of who should perform
videostroboscopy. In some clinic settings a speech-language pathologist rather than a
physician performs the examination. This option may be selected because of special
expertise, as a time-saving practice, or because of availability of equipment. At the very
least, an otolaryngologist should review the videotaped examination. Although we have
no doubt that many speech-language pathologists are capable of performing adequate oral
examinations, most do not perform TFL. We feel that TFL is essential to evaluate most
patients, and that it should be performed by the examining physician. Having direct
patient feedback during the examination, with the ability to adjust vocal tasks depending
on the initial findings and to focus the evaluation as determined by the clinical setting, is
essential to accurate diagnosis. We believe that it is especially important for the
otolaryngologist to perform his or her own examinations in surgical cases.
Laryngeal Electromyography
Laryngeal electromyography (LEMG) is an important diagnostic test that provides
essential information about the neuromuscular status of the larynx that no other test can
provide (1,2). Laryngeal electromyography can be performed quickly and accurately in
most cases. At our voice center, we use a team approach. The laryngologist places the
needle electrodes, the neurologist operates the EMG machine, and both interpret the
findings. We routinely test both the cricothyroid muscles (supplied by the superior
laryngeal nerves) and the thyroarytenoid muscles (supplied by the recurrent laryngeal
nerves). If indicated, other muscles can be tested. In performing LEMG, for each muscle
there are three parameters that are routinely evaluated: (a) recruitment, (b) waveform
morphology, and (c) the presence of spontaneous activity. The finding of spontaneous
activity is important, because it indicates ongoing neural degeneration. When it is
present, a concerted effort to find the cause of the paresis/paralysis is necessary. In the
absence of spontaneous activity, it can be presumed that the neural insult occurred in the
remote past. Management strategies and specific treatment recommendations are often
modified on the basis of such information. In particular, we use site-of-lesion information
gained from testing of the cricothyroid and thyroarytenoid muscles to direct the
subsequent radiographic evaluation. If the superior laryngeal nerves are affected, we
obtain a magnetic resonance image of the brain and skull base; if not involved, we obtain
a computed tomography scan (skull base through superior mediastinum).
In addition to determining site of lesion, LEMG also may indicate the prognosis in
paresis/paralysis, and it reliably differentiates paralysis from fixation. The finding of
plentiful, low-amplitude, polyphasic (nascent) motor units, for example, indicates
ongoing neural recovery and a good prognosis. On the other hand, markedly reduced
recruitment and large-amplitude motor units indicate a poor prognosis for full recovery.
In patients with vocal fold immobility/hypomobility, LEMG should be considered one of
the first and most important diagnostic tests. Other clinical findings and tests do not
answer a crucial question: is the hypomobility due to neural disease (paresis/paralysis) or
inflammation/scar (i.e., dislocation or fixation) of the arytenoid? Following endotracheal
intubation injuries, for example, LEMG differentiates between arytenoid dislocation and
paresis or paralysis.
A significant, new application for LEMG is in the diagnosis of vocal fold paresis.
Currently, this is the most common indication for obtaining LEMG in our practice.
Patients presenting with voice complaints such as vocal fatigue and decreased vocal
range that have subtle abnormalities on laryngeal (TFL) examination, or that have
hyperkinetic laryngeal conditions that defy voice therapy, commonly demonstrate
abnormal LEMG results. These findings indicate a primary neuromuscular etiology for
the voice problem. Without such testing, many such patients are dismissed as having
functional (behavioral) voice disorders.
Despite the ease and usefulness of LEMG, there is some resistance to its routine use in
clinical practice. We suspect that as experience with this diagnostic tool grows, it will
become an indispensable part of the practice of laryngology.
Laryngopharyngeal Reflux
There are few areas in otolaryngology that are as controversial as laryngopharyngeal
reflux (LPR). The controversy surrounds not only the diagnosis and treatment of LPR,
but also its role in causing or exacerbating laryngeal diseases. Koufman et al. (3)
prospectively studied 113 patients with laryngeal and voice disorders and found that 50%
had LPR documented by ambulatory double-probe (simultaneous esophageal and
pharyngeal) pH monitoring. The most striking finding in their study was that 88% of
patients with benign or malignant vocal cord lesions had pH-documented LPR.
There appear to be several reasons why patients with LPR remain underdiagnosed and
undertreated. It is becoming increasingly clear that the mechanisms of reflux in
otolaryngology patients with LPR are quite different from those seen in patients with
typical gastroesophageal reflux disease (GERD) (4). Traditionally, esophagitis and its
primary symptom heartburn were considered prerequisites for the diagnosis of reflux
disease. Most otolaryngology patients with LPR do not have esophagitis or heartburn
because they have upright (daytime) reflux with normal or near-normal esophageal acid
clearance. By comparison, traditional GERD patients with esophagitis have supine
(nocturnal) reflux with long esophageal exposure times to acid and pepsin (3).
The second reason that LPR is often underdiagnosed is that traditional diagnostic tests for
reflux are essentially tests for esophagitis. In a series of patients with LPR, Wiener et al.
(5) demonstrated that only 27% of dysphonic otolaryngology patients had abnormal
esophagoscopy and biopsy, but 77% had pH-documented LPR. Ambulatory double-probe
pH monitoring has become the gold standard for the diagnosis of LPR. Reflux events
outside the esophagus can be documented with the second probe placed in the
hypopharynx. Although this does not prove that LPR is the cause of any particular
laryngeal condition, the association between many conditions and LPR can be
demonstrated.
The third reason that LPR is underdiagnosed is that therapeutic trials with histamine (H
2
)
antagonists and low-dose proton pump inhibitors (PPIs) are often ineffective for LPR
patients. This is because most trials are only given for short periods of time, whereas LPR
often takes several months to treat. Additionally, traditional doses of these medications
are only partially effective in suppressing acid production (6). Since the introduction of
PPIs in the United States, several clinicians have reported their superiority to H
2

antagonists (7). PPIs have a different mechanism of action compared with H
2
antagonists.
PPIs inhibit the last stage of acid production to theoretically achieve near-total acid
suppression. Nevertheless, we have found that a significant proportion of patients fail
even high-dose PPI therapy (6). In such patients, surgical antireflux treatment
(fundoplication) remains the best viable option.
Clinicians have for years looked for posterior laryngitis (hypertrophic interarytenoid
mucosa and erythematous arytenoids) as the principal finding in LPR; however, edema
(and not erythema) is the principal finding of LPR. The most common findings of LPR
are effacement of the ventricles by the swollen false and true vocal cords, so-called
ventricular obliteration, and pseudosulcus vocalis (subglottic edema). Thus, clinicians
have underdiagnosed LPR because these findings were not recognized.
Reflux remains a controversial area. Double-probe pH testing, although it is the current
standard for diagnosis, will not positively identify LPR in every case. Patients with LPR
often have life-stylerelated or intermittent reflux events. LPR also has been implicated
in the pathogenesis of many pediatric diseases, including laryngomalacia, subglottic
stenosis, laryngospasm, and sudden infant death syndrome (8,9). These areas require
further investigation.
Flexible Endoscopic Evaluation of Swallowing versus Modified Barium Swallow
Traditional swallowing evaluations have relied on radiologic examinations because
accurate examination of the swallowing mechanism was not possible by other means.
Recent advances have allowed fiberoptic scopes to become smaller, and this led to the
development of flexible endoscopic evaluation of swallowing (FEES), direct endoscopic
visualization of the swallowing mechanism. FEES is typically performed by an
otolaryngologist or a speech-language pathologist, whereas the modified barium swallow
(MBS) usually is performed by a speech pathologist in conjunction with a radiologist.
Flexible endoscopic evaluation of swallowing is an excellent way of evaluating
swallowing, and it is significantly less expensive than MBS.
Although there is a concern about the amount of information that can be obtained from
the endoscopic approach (because the pharynx collapses on swallowing), one excellent
study has confirmed its accuracy and reliability (10). In addition, using a specially
designed laryngoscope, reproducible laryngopharyngeal sensory thresholds can be
determined. This is done by directing calibrated puffs of air to various locations in the
laryngopharynx. Laryngopharyngeal sensory discrimination testing, when combined with
the endoscopic swallowing evaluation, is commonly termed FEESST (flexible
endoscopic evaluation of swallowing with sensory testing). This technology may have
significant applicability for patients with dysphagia due to various causes and for the
evaluation of patients at potential risk for aspiration (e.g., following cerebrovascular
accidents) (10).
SURGICAL CONTROVERSIES
Vocal Process Granulomas
Vocal process granulomas may be unilateral or bilateral. Their etiology is multifactorial.
Because the vocal processes contact one another during phonation, the thin epithelium
overlying thin perichondrium may be traumatically injured by hyperkinetic laryngeal
behaviors. Likewise endotracheal tubes may abrade this mucosa, or LPR may lead to its
ulceration. LPR, endotracheal intubation, hyperfunctional compensation secondary to
vocal fold paresis, and vocal abuse have all been implicated, alone or in combination, as
causes for granulomas. It has become increasingly clear that the underlying causes of
granulomas must be identified and effectively treated for resolution to occur. Repeated
surgical removal is a fruitless surgical endeavor.
Surgery should be considered for vocal process granulomas under four conditions: (a) for
biopsy, when the possibility of carcinoma exists; (b) for airway obstruction, if the
granulomas are quite large; (c) if the granuloma matures and becomes a fibroepithelial
polyp; and uncommonly (d) to restore the voice in selected cases (when the granuloma
prevents vocal fold contact). Otherwise, treatment should focus on acid suppression with
PPIs and voice therapy. Even with effective treatment, granulomas may require 8 months
or longer to resolve.
Some investigators have suggested the use of botulinum toxin injection to prevent glottal
hyperfunction in recalcitrant cases wherein continued vocal trauma is implicated as the
primary cause of the persistent granuloma (11). We believe that it is important to rule out
other causes before this treatment to avert recurrence. Finally, some patients with
recalcitrant granulomas have unilateral vocal fold paresis, resulting in compensatory
hyperfunction. This diagnosis requires LEMG, and surgical treatment may be directed at
improving glottal closure.
Treatment of Early Carcinoma of the Vocal Fold
Radiation therapy remains the most commonly used treatment for T1 glottic carcinoma,
and in most cases it offers high cure rates with preservation of vocal function. However,
since the advent of the CO
2
surgical laser, the indications for laser surgery to treat vocal
fold carcinoma have expanded. Some surgeons prefer use of the laser for primary
excision of early carcinoma. These proponents suggest that laser resection offers several
advantages over irradiation and that the cure rates and voice results are comparable
(12,13). The reported advantages are surgical exploration of the lesion to reveal the true
extent of disease, simultaneous diagnosis (biopsy) and definitive treatment,
comparatively low cost, and outpatient treatment with the patient usually able to return to
work within days of surgery. Cost analysis studies suggest that laser surgery may be as
little as one tenth the cost of radiation therapy. In addition, fewer long-term
complications are reported with endoscopic resection, as compared with radiation
therapy. Finally, irradiation is retained as a future therapeutic option. McGuirt and
colleagues (13) compared the vocal results of patients treated by laser resection with a
comparable radiation therapytreated group. Although resection of half or more of the
vocalis muscle was associated with postoperative dysphonia, the overall voice results
were comparable or superior for the surgical group.
Contemporary diagnostic technology allows the laryngologist to select the most
appropriate surgical candidates. Preoperative videostroboscopy is essential in assessing
the feasibility of achieving a good postoperative voice. When the lesion is superficial, a
normal postoperative voice can be achieved if dissection can be confined to the Reinke
space. With more invasive lesions, resection may result in permanent dysphonia, but the
same is often true with radiation therapy. Although it is important to achieve clear
margins, wide excision of small lesions is unnecessary, and it can compromise the
postoperative voice. With endoscopic resection, it is imperative that the surgeon excise
and not ablate the lesion. Surgeons experienced with endoscopic techniques are more
likely to properly select patients for surgery. Patients also should participate in their
treatment selection.
Use of Polytef (Teflon) in Laryngology
After its introduction in 1962 by Arnold (14) Polytef or Teflon became popular for
injection augmentation of the paralyzed vocal fold. Unfortunately, such injections have
many drawbacks, including (a) Teflon granuloma formation (sometimes with airway
obstruction); (b) subsequent fixation of the arytenoid due to the inflammatory process; (c)
inability to close the posterior glottis; and (d) when endoscopic removal is attempted,
complete removal is not possible. Some clinicians believe all patients with Polytef
injections will develop Teflon granulomas eventually. In addition, most laryngologists
agree that Polytef should never be injected into a mobile vocal fold. Polytef injection
augmentation should not be considered a treatment for bowing or paresis of the vocal
folds. When Polytef is injected into a mobile fold, it appears to diffuse throughout all
layers and produce a stony hard vocal fold with gradual, progressive worsening of the
voice over time (15).
There are now two approaches for removing Polytef. Until recently an endoscopic
approach to the removal of Teflon granulomas was used. The goal of surgery was to
debulk the granuloma in order to improve the airway (when compromised) and to create a
straight edge for the contralateral vocal fold contact. Because Teflon usually remained
after the endoscopic procedure, recurrence of granuloma formation was common. A new
approach has been advocated that appears to be more successful. A laryngoplastic
approach to the paraglottic space allows complete removal of Teflon as well as
reconstruction of the vocal fold using a strap muscle flap (16). Some surgeons also use an
arytenoid adduction (AA) procedure at the same time. The results of this approach appear
to be excellent (16).
For paralytic dysphonia, medialization laryngoplasty (ML), with or without AA, has
become the preferred technique. When performed in conjunction with an AA, the
posterior larynx can be effectively closed. At present, we recommend Polytef injection
only for patients with limited life expectancy, such as those with terminal cancer.
Generally, laryngoplasty is considered the superior treatment for vocal fold paralysis.
Laryngoplastic Phonosurgery
Laryngoplastic phonosurgery is the term used to describe all forms of laryngeal
framework surgery to improve the voice (17). The concept of altering the voice by
surgical alteration of the laryngeal framework is not new, but this type of surgery has
received considerable attention in recent years because of renewed clinical interest in
voice disorders (18). Medialization laryngoplasty, unilateral or bilateral, offers new
options for patients with vocal fold bowing or deficient soft tissue with mobile folds (19).
These procedures are highly successful, but their place in the average otolaryngologist's
practice remains to be established.
Techniques of Medialization Laryngoplasty
Appropriately, implants for ML have not been standardized. We still use firm Silastic
block. Silastic is easy to custom carve, implant, modify, stabilize, and remove. In
addition, it is neither antigenic nor likely to migrate. In our opinion, materials such as
autologous cartilage and hydroxylapatite are not really suitable for ML surgery. These
implants are rigid and difficult to customize, and the ability to reverse or revise an ML
performed with hydroxylapatite is highly questionable. In addition, although preformed
implants are commercially available, we believe that good surgical results require that the
surgeon customize each implant for each patient. Gore-Tex has recently become a
popular implant material. The advantage of this material is that it can be adjusted in situ
without causing significant edema and that it requires less skill than carving a Silastic
implant. Although we have been pleased with our early results with Gore-Tex
laryngoplasty, it still does not seem to offer sufficient precision for some cases of vocal
fold bowing.
Among experienced laryngoplastic surgeons, there is no consensus on the technique of
ML window formation, implant formation (shape and size), and implant material. This
lack of consensus seems appropriate, because ML requires the same surgical judgment
and precision in addressing the anatomic problem as reconstructive facial plastic surgery.
Laryngoplasty is still a relatively new part of operative laryngology, so it is likely that
ML technique will continue to evolve. It is important to realize that, despite the implant
design, it is impossible to close the posterior glottis with ML alone. When the posterior
larynx is open, AA, a unique procedure that also restores vocal fold length and height, is
indicated (20). Like ML, there is also no single well-accepted technique for the
performance of this procedure.
In the hands of some surgeons, the cricoarytenoid joint is routinely opened, whereas
others discourage this practice. Those who open the joint claim that this releases the
arytenoid's lateral attachments so that the medial and posterior muscular attachments can
help reestablish appropriate arytenoid positioning. This issue is not likely to be resolved
in the near future. More important is the question of whether the AA procedure should be
performed. Most experienced laryngologists who use this procedure believe it is not
reversible and thus should not be performed unless the cause of the paralysis is believed
to be permanent.
There is also controversy as to the timing of laryngoplasty after skull base resection.
Some clinicians prefer performing an ML at the end of the oncologic procedure (21),
whereas others prefer to wait a few days or weeks until the patient can tolerate a
local/stand-by (combined ML and AA) procedure. We favor the latter approach for
several reasons. First, ML and AA add time to an already lengthy procedure. Second, it is
preferable to do the ML/AA with the patient awake and able to phonate. And third, the
AA cannot be performed as well with an endotracheal tube in place. We recommend
placing a feeding tube, but not a tracheotomy, in the patient with aspiration, and
performing the ML/AA procedure when the patient can first tolerate a local/stand-by
procedure, usually within 2 weeks of the major resection. We believe that the results of
this approach are superior.
Microlaryngeal Surgery
The linkage of the CO
2
laser with the operating microscope revolutionized
microlaryngeal surgery, rendering many open surgical procedures obsolete. However,
until introduction of the microspot, there was debate among laryngologists about whether
the CO
2
laser should be used in delicate phonosurgical vocal fold procedures or in
professional voice users. It is important to recognize, however, that the precision of the
surgical technique depends only partially on the technology of the instrumentation.
Clearly, there are lesions for which the CO
2
laser is the surgical instrument of choice,
including recurrent laryngeal papillomas, vascular lesions, false vocal cord cysts, and
early vocal cord carcinoma. For other lesions, use of the laser depends mainly on the
surgeon's training and preferences.
Removal of a submucosal vocal cord cyst or decortication of Reinke edema can be
accomplished with or without the use of the laser. Some surgeons prefer to use the laser
for only a part of these procedures (e.g., to make incisions, coagulate vessels). Currently,
the CO
2
laser should be viewed as a surgical instrument that has specific properties, and
selection of technique should be on a case-by-case basis. The use of surgical lasers
(particularly the CO
2
laser) in the phonosurgical treatment of benign lesions remains
controversial. Some surgeons claim that the thermal damage created by the laser impairs
the surgical result, whereas others claim that the use of the laser in the hands of judicious
surgeons is like any other tool. In a recent study, Benninger (22) found that the surgical
result was no different when using either cold microdissection or the laser for removal of
a variety of lesions. This report suggests that differences in outcome may be related more
to surgical technique and experience than to instrumentation.
There is little controversy about which type of laser to use in the larynx for vocal fold
surgery. CO
2
laser energy is absorbed by water. It is preferred to shorter wavelength
lasers such as the KTP/532 or neodymium:yttrium-aluminum-garnet (Nd:YAG) laser.
This property gives the CO
2
laser a special advantage because the Reinke space contains
watery, gelatinous material, which provides a natural barrier (heat sink) to thermal injury
of the underlying vocal ligament and muscle. Thus, the CO
2
laser remains the laser of
choice, with the admonition that a relatively low-power density should be used when
operating on the vocal folds.
Lipoinjection
The use of autologous fat for injection augmentation of the vocal fold has become an
accepted tool in the laryngologist's surgical armamentarium. There are several areas of
concern, however, including the optimal technique for graft harvest and injection; the
relatively poor long-term yield (graft take); and the inability to control fat cell graft
distribution in injected tissue. Nevertheless, lipoinjection is currently being used to
augment the paralyzed vocal fold, particularly in children (23), for paretic or bowed vocal
folds, and for scarred vocal folds.
The reported techniques of fat graft harvest and preparation differ greatly. Mikus et al.
(24) compared liposuction versus purification by fat homogenization and centrifugation
in a buffer and found liposuction to be superior. Others use various combinations of
manual or machine liposuction, gentle separation and morselization, and washing away
free fat, blood, and cellular debris prior to injection. It is clear, however, that broken
adipocytes release fatty acids and triglycerides, which engender an intense inflammatory
response in normal tissue. The optimal technique should retain clumps of viable
adipocytes and remove as much of the free fat as possible. We recommend the following:
(a) adipose tissue is removed from the abdomen by liposuction; (b) the graft then is
combined in equal amounts with previously obtained autologous serum (containing
albumen, which buffers and binds free fatty acids and triglycerides); (c) the graft/serum
mix is centrifuged for 10 minutes; and (d) the middle layer, which contains the intact fat
cells, is used for injection. Using this technique, the mean long-term yield is 35% (range
10% to 60% by volume.) Other reports also suggest that injection yields are less than
50%; so overinjection is always recommended. Also reported is a technique of
implantation of adipose tissue into a pocket developed in the superficial layer of the vocal
cord (25). Adipose tissue appears to be an excellent graft material; however, additional
research needs to be carried out in this area.
Surgery for Spasmodic Dysphonia
Treatment of SD has relied on botulinum toxin injection into various laryngeal muscles.
Although results have been good with such treatments, patients were required to have
injections every few months. Some laryngologists have developed surgical procedures for
the treatment of adductor-type SD. Although some of these procedures are now obsolete
[i.e., recurrent laryngeal nerve (RLN) section], others are only beginning to be explored.
A modification of the RLN section procedure has been described (26) that involves
sectioning selected branches of the nerve to the thyroarytenoid muscle. In theory, this
procedure affects only those branches of the nerve that are responsible for the patient's
symptoms. The results of this procedure are still preliminary, and there is concern that
these patients may have a recurrence of symptoms, as did most of the patients who
underwent total RLN sections.
Surgical procedures also have been developed for abductor-type SD. Both bilateral ML
and lipoinjection have been used to better approximate the vocal folds to prevent the
flying abductions that occur in abductor-type SD. We also have reported an endoscopic
procedure [endoscopic partial posterior cricoarytenoid (PCA) myectomy] to surgically
weaken the PCA muscle in such patients (27). Similar myectomy procedures have been
described for the thyroarytenoid muscle in the treatment of adductor-type SD patients
(28).
These procedures are new and not widely used, in part because botulinum toxin injections
are so effective in treating the majority of patients, and because the results of such
surgical procedures for SD are somewhat variable. Their use remains controversial.
Office-Based Laryngeal Surgery
With advancements in instrumentation, it has become increasingly possible to perform
endolaryngeal surgery in the office setting. As experience grows in such techniques,
surgeons are continuing to push forward. More aggressive procedures are being
performed outside of the operating room, including removal of vocal process granulomas;
vocal fold polyps; injection augmentation; and surgery for Reinke edema. Obvious
concerns have been raised as to the safety of such procedures, specifically with regard to
the risk of airway obstruction. Additionally, the ability to perform careful dissection with
the preservation of normal mucosa is limited when performing awake peroral lesion
removal. This may lead to scarring and poor voice outcome. We recommend the
judicious use of such office-based procedures.

HIGHLIGHTS
Transnasal fiberoptic laryngoscopy allows evaluation of
laryngeal biomechanics, which is not possible with oral
examination using rigid telescopes.
Advances in videostroboscopy, acoustic voice analysis, and
LEMG have refined the clinician's ability to diagnose and treat
patients with voice disorders.
Laryngeal electromyography provides information regarding
the neuromuscular integrity of the larynx and is important for
the evaluation of vocal fold immobility and paresis.
Laryngopharyngeal reflux is commonly associated with
laryngeal dysfunction. In otolaryngology patients, it is often
occult and may produce extraesophageal symptoms without
producing typical gastrointestinal symptoms, such as heartburn.
Flexible endoscopic evaluation of swallowing and FEESST are
new tests that allow the clinician to evaluate patients with
swallowing disorders. Eventually, these tests may obviate the
need for the MBS.
Vocal process granulomas are the result of LPR, vocal abuse,
endolaryngeal trauma, and compensatory behaviors for
underlying glottal hypofunction. They usually resolve with
conservative nonsurgical therapy.
Endoscopic laser surgery is recommended for early vocal cord
carcinoma as an efficient and inexpensive alternative to
radiation therapy.
The recommended surgical approach for rehabilitation of
patients with vocal cord paralysis is ML, which is a reversible
procedure.
CHAPTER REFERENCES
1. Postma GN, Koufman JA. Laryngeal electromyography. Curr Opin Otolaryngol Head Neck Surg
1998;6:411415.
2. Koufman JA, Walker FO. Laryngeal electromyography in clinical practice: indications,
techniques, and interpretation. Phonoscope 1998;1:5770.
3. Koufman JA, Amin MR, Panetti M. Prevalence of reflux in 113 consecutive patients with
laryngeal and voice disorders. Otolaryngol Head Neck Surg 2000;123:385388.
4. Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a
clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an
experimental investigation of the role of acid and pepsin in the development of laryngeal injury.
Laryngoscope 1991;101:178.
5. Weiner GJ, Koufman JA, Wu WC, et al. Chronic hoarseness secondary to gastroesophageal reflux
disease: documentation with 24-H ambulatory pH monitoring. Am J Gastroenterol 1989;84:12.
6. Amin MR, Postma GN, Johnson PE, et al. Proton pump inhibitor resistance in the treatment of
reflux. Otolaryngol Head Neck Surg (submitted for publication).
7. Jansen JB, Van Oene JC. Standard-dose lansoprazole is more effective than high-dose ranitidine in
achieving endoscopic healing and symptom relief in patients with moderately severe reflux
oesophagitis. The Dutch Lansoprazole Study Group. Aliment Pharmacol Ther 1999;13:1611
1620.
8. Little JP, Matthews BL, Glock M, et al. Extraesophageal manifestations of pediatric reflux: a 24-
hour double-probe pH study of 222 children. Ann Otol Rhinol Laryngol 1997;169:116.
9. Loughlin CJ, Koufman JA, Averill DB, et al. Acid-induced laryngospasm in a canine model.
Laryngoscope 1996;106:15061509.
10. Aviv JE. Prospective, randomized outcome study of endoscopy versus modified barium swallow
in patients with dysphagia. Laryngoscope 2000;110:563574.
11. Nasri S, Sercarz JA, McAlpin T, et al. Treatment of vocal fold granuloma using botulinum toxin
type A. Laryngoscope 1995;105:585588.
12. Simpson CB, Postma GN, Stone RE, et al. Speech outcomes after laryngeal cancer management.
Otolaryngol Clin North Am 1997;30:189205.
13. McGuirt WF, Blalock D, Koufman JA, et al. Comparative voice results after laser resection or
irradiation of T1 vocal cord carcinoma. Arch Otolaryngol Head Neck Surg 1994;120:951955.
14. Arnold GE. Vocal rehabilitation of paralytic dysphonia. Arch Otolaryngol 1962;76:358368.
15. Nakayama M, Ford CN, Bless DM. Teflon vocal fold augmentation: failures and management in
28 cases. Otolaryngol Head Neck Surg 1993;109:493498.
16. Netterville JL, Rainey CL, Coleman JR, et al. Lateral laryngotomy for the removal of Teflon
granuloma. Ann Otol Rhinol Laryngol 1998;107:735744.
17. Koufman JA, Isaacson G. Laryngoplastic phonosurgery. Otolaryngol Clin North Am
1991;24:11511177.
18. Netterville JL, Stone RE, Luken ES, et al. Silastic medialization and arytenoid adduction: the
Vanderbilt experience, a review of 116 phonosurgical procedures. Ann Otol Rhinol Laryngol
1993;102:413424.
19. Postma GN, Blalock PD, Koufman JA. Bilateral medialization laryngoplasty. Laryngoscope
1998;108:14291434.
20. Isshiki N, Tanabe M, Sawada M. Arytenoid adduction for unilateral vocal cord paralysis. Arch
Otolaryngol 1978;104:555558.
21. Netterville JL, Jackson CG, Civantos F. Thyroplasty in the functional rehabilitation of neuro-
otologic skull base surgery patients. Am J Otol 1993;14:460464.
22. Benninger MS. Microdissection or microspot CO
2
laser for limited vocal fold benign lesions: a
prospective randomized trial. Laryngoscope 2000;110 [erratum 2000;110:696].
23. McGuirt WF Jr, Jacob SL, Puri SK, et al. Autologous fat injection in the pediatric larynx:
indications and technique. Arch Otolaryngol (in press).
24. Mikus JL, Koufman JA, Kilpatrick SE. Fate of liposuctioned and purified autologous fat injections
in the canine vocal fold. Laryngoscope 1995;105:1722.
25. Sataloff RT, Spiegel JR, Hawkshaw M, et al. Autologous fat implantation for vocal fold scar: a
preliminary report. J Voice 1997;11:238246.
26. Berke GS, Blackwell KE, Gerratt BR, et al. Selective laryngeal adductor denervation
reinnervation: a new surgical treatment for adductor spasmodic dysphonia. Ann Otol Rhinol
Laryngol 1999;108:227231.
27. Koufman JA. Preliminary report: management of abductor spasmodic dysphonia by endoscopic
partial posterior cricoarytenoid (PCA) myectomy. Phonoscope 1999;2:159164.
28. Genack SH, Woo P, Colton RH, et al. Partial thyroarytenoid myectomy: an animal study
investigating a proposed new treatment for adductor spasmodic dysphonia. Otolaryngol Head
Neck Surg 1993;108:256264.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

56 ESOPHAGEAL DISORDERS
Head & Neck SurgeryOtolaryngology
56




ESOPHAGEAL DISORDERS
WILLIAM W. SHOCKLEY
AUSTIN S. ROSE

W.W. Shockley and A.S. Rose: Division of OtolaryngologyHead and Neck Surgery, University of North
Carolina Medical Center, Chapel Hill, North Carolina.


Esophageal Form and Function
Anatomy
Physiology
Upper Esophageal Sphincter
Lower Esophageal Sphincter
Evaluation and Diagnosis
Symptoms
Physical Examination
Laboratory Tests
Radiologic Studies
Esophageal Manometry
pH Monitoring
Endoscopic Examination
Gastroesophageal Reflux Disease
Evaluation
Treatment
Complications of Reflux
Esophageal Motility Disorders
Achalasia
Diffuse Esophageal Spasm
Scleroderma
Cricopharyngeal Dysfunction
Esophageal Webs and Rings
Diverticula
Infectious and Inflammatory Conditions
Benign Neoplasms and Cysts
Esophageal Carcinoma
Complications and Emergencies
Perforation and Rupture
Hemorrhage
Mediastinitis
Obstruction
Chapter References
The purpose of this chapter is to briefly review the anatomy and physiology of the
esophagus, and to discuss the evaluation, diagnosis, and treatment of the remarkable
array of esophageal diseases.
ESOPHAGEAL FORM AND FUNCTION
Anatomy
The esophagus is a mucosally lined neuromuscular tube that provides transportation of
food from the mouth and pharynx to the stomach. It is often considered in segments: the
upper third, middle third, and lower third. Beginning in the lower neck, the esophagus
traverses the posterior mediastinum and enters the abdominal cavity through the
esophageal hiatus of the diaphragm. There are three regions of natural constriction: the
cricopharyngeus, the point at which the aorta and left mainstem bronchus cross
anteriorly, and the lower esophageal sphincter (LES). The cricopharyngeus is the
narrowest point in the entire gastrointestinal tract.
The esophagus is composed of an outer muscular layer, a middle layer of submucosa, and
an inner mucosal layer. The upper third of the muscular layer is striated, whereas the
lower two thirds are composed of smooth muscle. The muscular layer can be further
divided into outer, longitudinal and inner, circular fibers. The mucosa is also a three-
layered system, including the muscularis mucosae, lamina propria, and epithelium.
Stratified squamous epithelium lines the majority of the esophagus, with only the distal 1
to 3 cm lined by columnar epithelium. An important feature of esophageal anatomy is the
absence of a serosal liningan important anatomic barrier to the spread of infection and
neoplastic disease that exists in the remainder of the abdominal-pelvic portion of the
gastrointestinal tract. Without a serosal layer, the esophagus is more susceptible to
perforation during instrumentation and has less structural integrity to aid in surgical
repair or anastomoses.
The blood supply of the esophagus follows a segmental organization (Table 56.1),
although there is great individual variation in the pattern. The nature of this blood supply
can be associated with significant ischemia if extensive surgical mobilization is
undertaken. The lymphatic drainage does not follow this segmental pattern. The cervical
esophagus tends to drain to the paraesophageal cervical nodes and then to the lower
jugular nodes. The lymphatic channels from the thoracic esophagus drain to superior
mediastinal, peribronchial, hilar, or paraesophageal nodes. The abdominal esophagus
drains into the left gastric nodes and the celiac nodes.

TABLE 56.1. BLOOD SUPPLY TO THE
ESOPHAGUS



The esophagus is innervated by the vagus nerve (parasympathetic) and sympathetic
chain. The cervical esophagus receives innervation from the recurrent laryngeal nerves.
In the superior mediastinum, the vagus nerves arborize to form an esophageal plexus.
These fibers then coalesce, forming two vagal trunks: the left anterior vagus and the right
posterior vagus. Motor function is thought to be under vagal control, although the role of
the sympathetic nerves is not well understood.
Physiology
In addition to the prevention of regurgitation and ventilation of excess gaseous materials
from the stomach, the primary function of the esophagus is the transportation of nutrients
during the esophageal phase of swallowing. As the pharyngeal constrictors contract, the
upper esophageal sphincter (UES) relaxes, propelling food into the esophagus and
initiating a peristaltic wave. This is known as primary peristalsis, and the contraction
proceeds distally along the length of the esophagus at a rate of approximately 5 to 10 cm
per second. Secondary peristalsis clears any remaining food and is initiated by
esophageal distention or by gastroesophageal reflux. Tertiary contractions are
nonperistaltic and can occur spontaneously or after swallowing. The normal swallow is a
highly coordinated sequence of events orchestrated through the swallowing center in the
medulla, and requires input from cranial nerves V, VII, IX, X, and XII. Lesser roles are
played by both gravity and the relative negative pressure in the lower esophagus.
Upper Esophageal Sphincter
Understanding the physiology of the UES and LES is essential to comprehending the
reflux and motility disorders that affect the esophagus. The cricopharyngeus muscle
originates from the posterolateral aspects of the cricoid cartilage, forming the UES.
Coordinated relaxation and contraction of the cricopharyngeus occur with normal
deglutition, allowing passage of food from the pharynx into the upper esophagus. The
UES is maintained in a constant state of contraction. Manometry has confirmed the
radial asymmetry of the UES; resting pressures in the anteroposterior orientation
average 100 mm Hg, whereas laterally oriented pressures are less than 50 mm Hg (1).
The high resting pressure of the UES is important because the body of the esophagus
maintains a resting pressure of -5 mm Hg due to its intrathoracic location. The resting
state of contraction of the UES prevents air influx during the normal respiratory cycle. If
the body of the esophagus is exposed to acid or if volume changes occur (e.g., fluid bolus
or balloon distention), the UES pressure increases significantly. These reflexes prevent
regurgitation and possible aspiration.
Lower Esophageal Sphincter
The LES is the most studied segment of the esophagus. It functions through a
combination of anatomic and physiologic factors, preventing the reflux of gastric
contents into the lower esophagus. During swallowing, the LES relaxes, allowing
ingested material to reach the stomach. The LES is a zone of increased pressure that is 2
to 4 cm long. The normal resting pressures range from 10 to 40 mm Hg. Incompetency of
the LES can lead to gastroesophageal reflux disease (GERD) and its associated
complications. If the LES fails to relax properly, dysphagia results and esophageal
motility is adversely affected.
There is significant debate about whether a discrete anatomic sphincter exists at the LES.
The anatomic features thought to play a role in competence of the LES include the
phrenoesophageal membrane, the gastric sling fibers, the right diaphragmatic crus, the
length of intraabdominal esophagus, and the mucosal folds at the gastroesophageal
junction. Many researchers think maintenance of the LES below the diaphragm may be
the single most important factor in preventing reflux. Up to 80% of patients with
symptomatic reflux have a hiatal hernia, primarily a type I or sliding hiatal hernia in
which the gastroesophageal junction and a portion of the stomach are allowed to slide
into the mediastinum.
Muscular, neural, and hormonal factors all contribute to the physiologic regulation of
LES pressure. Although it does not play a major role, there is intrinsic myotonic activity
of the smooth muscle. Neural control is regulated through inhibitory and excitatory
autonomic nerves. Alpha-adrenergic neurotransmitters increase LES pressure and -
adrenergic blockers decrease it; -adrenergic stimulation decreases LES pressure and -
adrenergic blockers increase it. Cholinergic mechanisms also exert control over resting
LES pressure. Hormonal regulation has been studied extensively, and dozens of
hormones and peptides have been found to influence LES pressure. Protein meals and
antacids tend to increase LES pressure, whereas fatty meals, chocolate, ethanol, smoking,
and caffeine are known to decrease LES pressure.
EVALUATION AND DIAGNOSIS
Symptoms
The most common symptoms associated with esophageal disorders are dysphagia and
heartburn. Patients with motility problems or obstructive lesions typically complain of
difficulty in swallowing. Odynophagia, or pain with swallowing, denotes inflammatory
changes of the esophageal mucosa. Those with significant GERD notice heartburn,
characterized as retrosternal burning pain and typically occurring within 30 to 45 minutes
of the end of a meal. The pain usually begins in the epigastric region, but may radiate into
the chest, throat, and arm. Regurgitation, another symptom of GERD, refers to the
spontaneous and retrograde passage of esophageal or gastric contents into the pharynx or
mouth, producing a bitter or sour taste. Patients with GERD or esophageal spasm also
may experience chest pain. Although uncommon, hematemesis and melena indicate a
serious esophageal disorder. Some esophageal diseases may be asymptomatic until they
reach an advanced stage; therefore, even trivial complaints of recent onset should be
taken seriously.
Physical Examination
Physical examination should include a complete examination of the head, neck, chest,
and abdomen. Indirect or flexible laryngoscopy can confirm proper vocal cord function;
paralysis may indicate compression or invasion of the recurrent laryngeal nerves.
Obstructive esophageal lesions may manifest as pooling of secretions in the
hypopharynx. Lower cervical and paratracheal adenopathy can be associated with a
cervical esophageal neoplasm.
Laboratory Tests
Laboratory studies are generally of limited value in the evaluation of dysphagia.
However, a complete blood count can demonstrate the anemia associated with
malignancy or Plummer-Vinson syndrome. Appropriate immunologic studies are
indicated if collagen-vascular disease is suspected.
Radiologic Studies
Barium swallow (i.e., full-column esophagography) remains one of the most useful tools
in screening for esophageal problems. This examination provides information about
esophageal motility, integrity of the lumen, and aspiration. Strictures, webs, tumors,
ulcers, diverticula, and extrinsic masses are readily visualized using this technique. For
subtle disorders of swallowing, a modified barium swallow can be performed, using
barium paste, cookies, or pellets of various sizes. Air-contrast barium studies can
demonstrate small esophageal lesions and subtle mucosal irregularities, such as those
seen in esophagitis. Mucosal relief radiography is performed by coating the esophagus
with a dense barium suspension or paste, and films are taken with the esophagus
collapsed. This technique is most useful for esophageal varices. Video recording of the
barium studies greatly enhances their capabilities and is particularly helpful in studying
motility disorders. The oral and pharyngeal phases of swallowing also can be studied,
providing a useful tool in the evaluation of dysphagia.
Computed tomography (CT) scanning is useful in the detection of neoplasms affecting
the esophagus. CT of the chest and abdomen can be used to determine the extent of an
esophageal carcinoma and to evaluate associated adenopathy. CT also can be used for
further evaluation of extrinsic compression of the esophagus detected by barium swallow.
The role of magnetic resonance imaging (MRI) in esophageal disease has been the
subject of ongoing research. MRI may offer greater accuracy in determining the depth of
cancer invasion. This was supported by a recent study in which accuracy was improved
using contrast particles coated with monoclonal antibodies directed against epidermal
growth factor receptors, which are overexpressed in esophageal squamous cell carcinoma
(2).
Esophageal Manometry
Manometric studies are useful in evaluating esophageal motility disorders. A narrow
catheter is introduced into the esophagus that can be used to take pressure measurements
at various points along its length. A manometric tracing can then be recorded that
demonstrates the amplitude and velocity of the peristaltic wave as well as the constriction
and relaxation of the UES and LES.
pH Monitoring
Twenty-four hour pH monitoring can provide significant information about a patient in
whom reflux is suspected. A pH electrode is introduced through the nose and placed
exactly 5 cm above the LES. In this technique, reflux is defined as lowering the pH to 4.1
at a level 5 cm above the LES. A normal total reflux time is less than 1 hour during a 24-
hour period. Although 24-hour pH monitoring provides the standard in the diagnosis of
reflux, 12-hour and postprandial modifications also have been developed. Monitors with
multiple pH sensors also have been used to demonstrate pH changes due to reflux in the
pharynx, characteristic of laryngopharyngeal reflux (LPR) (3).
Endoscopic Examination
The esophagus can be examined directly by esophagoscopy. Both rigid and flexible
instrumentation is available, each with inherent capabilities. The relative advantages and
disadvantages of the two techniques are outlined in Table 56.2. Rigid esophagoscopy
provides a portal for larger, deeper, and sometimes more informative biopsies, and allows
easier removal of most foreign bodies. The endoscope itself is more durable, cheaper, and
easier to maintain. Flexible endoscopes are slightly safer to insert, better tolerated under
topical anesthesia, and capable of passing through more tortuous anatomy, allowing
evaluation of the esophagus, stomach, and duodenum. The optical system provides a
more detailed view of mucosal abnormalities and easy documentation with endoscopic
photography. A summary of the diagnosis and treatment of various esophageal disorders
is provided in Table 56.3 and Table 56.4, respectively.

TABLE 56.2. ADVANTAGES OF RIGID AND
FLEXIBLE ESOPHAGOSCOPY



TABLE 56.3. DIAGNOSIS ESOPHAGEAL
DISORDERS



TABLE 56.4. TREATMENT ESOPHAGEAL
DISORDERS



GASTROESOPHAGEAL REFLUX DISEASE
Evaluation
Gastroesophageal reflux disease refers to the symptoms or pathologic findings caused by
the reflux of gastric contents into the esophagus. It is relatively common, with one third
of adults reporting occasional symptoms and 10% with daily symptoms. Understanding
this problem is possible only with familiarity of the LES, its functions, and the factors
contributing to its competence.
The most common symptom of reflux is heartburn. Sixty-one million Americans, or 44%
of the adult U.S. population, experience heartburn at least once a month (4). Typically,
the pain is epigastric, although retrosternal symptoms are common and may mimic
cardiac symptoms. Patients also may complain of pain referred to the back, arm, fingers,
and ear. Symptoms usually occur after meals and may last 20 minutes to 2 hours. Fatty
and spicy foods or a large meal are common precipitating factors. Postural changes also
may induce symptoms. As the disease progresses, dysphagia may become a dominant
clinical feature. Slowly progressive dysphagia for solids suggests the development of a
peptic stricture, whereas dysphagia for both liquids and solids suggests a GERD-related
motility disorder.
Incompetence of the LES was discussed previously and is the single most important
factor in GERD. Prompt esophageal clearance diminishes contact time with the mucosa
and minimizes deleterious effects. The rate of clearance depends on gravity, esophageal
peristalsis, and salivation. Because reflux depends on a reservoir of gastric fluid, the
volume of fluid and the rate of gastric emptying are other determining factors in the
frequency and severity of GERD. The symptoms of delayed gastric emptying include
early satiety, bloating, fullness, and epigastric discomfort. Smoking and high-fat meals
may further delay gastric emptying, increasing the potential for reflux.
Tissue resistance of the esophageal epithelium is a factor in the development of reflux
esophagitis. Normal squamous epithelium provides a protective barrier, but with reflux of
acid, bile, and pepsin, both inflammation and denaturization of proteins can occur. This
leads to a breakdown of the epithelium. The capacity of normal epithelium to withstand
this injury and its capability to regenerate are affected by multiple constitutional factors
and dietary habits.
Initiation of empiric therapy is justified in the patient with classic GERD symptoms.
Diagnostic tests should be limited to patients with atypical or recurrent symptoms as well
as patients with associated complications. Indications for diagnostic testing are listed in
Table 56.5. Ambulatory 24-hour pH monitoring, the gold standard diagnostic test for
GERD, allows quantification of reflux and correlation with symptoms. Barium swallow
is the best initial diagnostic study for patients who have dysphagia and reflux symptoms,
and is particularly helpful in identifying anatomic lesions, such as a hiatal hernia or
strictures. Esophagoscopy is helpful in evaluating mucosal injury and is the preferred
method for identifying esophagitis or Barrett's esophagus. Esophagoscopy reveals
evidence of reflux esophagitis in 50% to 65% of patients with GERD. In one study, 100
patients referred to a surgical clinic with symptoms of GERD were prospectively
evaluated with esophagoscopy. According to the Savary Miller classification, grade I
esophagitis (erythema) was seen in 26%, grade II (< 10% erosion) in 8%, grade III
(>10% erosion) in 7%, and grade IV (ulcer or stricture) in 10%. Barrett's esophagus was
noted in 8% of the patients with advanced grades of esophagitis (5).

TABLE 56.5. GERD: INDICATIONS FOR
DIAGNOSTIC TESTS



Treatment
Several life-style modifications are commonly recommended to patients with symptoms
of GERD. Patients with reflux should avoid lying down soon after meals and should keep
the head of their bed elevated 15 to 20 cm. Weight reduction and avoidance of fatty foods
are helpful, as are smaller meals. Other measures include avoidance of substances that
decrease LES pressure, such as chocolate, peppermint, cigarettes, and caffeine.
Potentially harmful medications include nitrates, theophylline, and calcium channel
blockers, which may decrease LES pressure, as well as doxycycline, quinidine, and
nonsteroidal antiinflammatory drugs (NSAIDs), which may induce mucosal injury (6,7).
The medical treatment of GERD includes the use of histamine receptor (H
2
) antagonists
and proton pump inhibitors. Histamine receptor antagonists, such as ranitidine, suppress
acid production, reducing reflux symptoms and the risk of esophagitis. The ability of
existent esophagitis to heal also parallels the degree of acid suppression. Further
reduction in intraesophageal pH is noted with divided doses of H
2
receptor blockers.
Proton pump inhibitors, such as omeprazole, offer the best control of esophageal acid
exposure. Studies have demonstrated 95% healing of esophagitis compared with 35% to
65% in patients treated with ranitidine 150 mg twice daily (8,9). Proton pump inhibitors
are often used as a first-line medical treatment for complicated GERD. Both increased
and divided doses are commonly used to treat the extraesophageal manifestations of
GERD, such as reflux laryngitis. Cisapride is a gastrointestinal prokinetic used
extensively in the past, primarily in pediatric patients, to treat GERD through its effect on
delayed gastric emptying. More recently, however, the use of cisapride has fallen out of
favor due to concerns about its safety, especially in patients with a history of cardiac
dysrhythmias, and its interactions with other drugs (10). Because GERD is potentially a
life-long disease, it seems prudent to treat relapses intensively, while encouraging long-
term changes in life-style and eating habits in an attempt to keep ongoing drug therapy to
a minimum.
Surgery is reserved for patients who fail medical therapy or who have complications of
GERD. Patients committed to a life-long course of medical therapy are often considered
for antireflux surgery. Diagnostic workup, including esophageal manometry, should
always be performed prior to antireflux surgery to exclude any concomitant motility
disorders. In the United States, the most commonly performed antireflux surgery is the
Nissen fundoplication. A randomized, prospective Veterans Administration cooperative
study demonstrated that surgery provided more effective remission of heartburn than
continuous medical therapy in patients with severe esophagitis over a 2-year period (11).
A retrospective review of 88 patients who underwent laparoscopic fundoplication
demonstrated that 77 patients (88%) remained asymptomatic and off all medication up to
3 years following surgery. The complication rate in this series was 2.3% (12). Treatment
options are summarized in Table 56.6.

TABLE 56.6. ANTIREFLUX THERAPY



Complications of Reflux
Complications in patients with GERD are fortunately uncommon, but those that do occur
may be serious. Long-standing reflux esophagitis can lead to esophageal stricture, which
may require periodic dilation and possibly surgical intervention. Esophageal ulceration
may result in pain that is constant and severe and unrelieved by antacids, as well as
esophageal hemorrhage. Many respiratory conditions are associated with aspiration
secondary to GERD, including chronic cough, bronchitis, aspiration pneumonia,
bronchiectasis, nocturnal dyspnea and asthma. A serious complication of Barrett's
esophagus is esophageal adenocarcinoma, which may develop in up to 10% of patients.
Patients with Barrett's esophagus should undergo routine endoscopy with biopsies to rule
out adenocarcinoma, as well as medical treatment to prevent progressive metaplasia.
Surgical fundoplication may be indicated in certain patients.
Koufman provided an exhaustive study of the laryngeal symptoms associated with reflux,
commonly referred to as LPR (6). Posterior laryngitis is a manifestation of the irritation
caused by refluxed material on the posterior structures of the larynx. Hoarseness, frequent
throat clearing, and cough are common complaints and are usually worse in the morning.
There also may be a vague throat discomfort or intermittent choking sensation. Early
physical findings include posterior laryngeal edema and erythema. Later signs include
ulceration and hyperkeratosis, particularly in the interarytenoid area. Contact ulcers,
Reinke edema, and laryngeal granulomas are all conditions associated with GERD. Also
associated with reflux are cricopharyngeal dysfunction, paroxysmal laryngospasm, and
pharyngoesophageal diverticula. There is some evidence that LPR also may be a risk
factor for laryngeal cancer (13). Proton pump inhibitors have been shown to be effective
in treating the symptoms of LPR in addition to GERD (14).
ESOPHAGEAL MOTILITY DISORDERS
Achalasia
Achalasia is a neuromuscular disorder associated with degeneration of the ganglion cells
of the Auerbach plexus. The exact pathophysiology leading to this condition is poorly
understood, but the hallmarks include aperistalsis, esophageal dilatation, and failure of
the LES to relax. This results in slowly progressive, intermittent dysphagia associated
with chest or epigastric pain. Eventually, regurgitation occurs, leading to cough,
aspiration, pneumonitis, and lung abscess. Achalasia tends to affect men and women
equally and is most common between the ages of 30 and 70. Late symptoms also may
include anemia, bleeding, weight loss, and psychological changes related to chronic
dysphagia.
The primary pathologic problem in achalasia is the functional obstruction caused by
nonrelaxation of the LES and hypertrophy of the smooth muscle fibers in the outer
circular layer of the lower two thirds of the esophagus. As the disease progresses,
contractions become asynchronous and nonperistaltic. In advanced stages, the muscle
becomes fibrotic and atrophic. This combination of factors leads to chronic food retention
and stagnation. The result is retention esophagitis, characterized by the endoscopic
findings of mucosal hyperemia, thickening, and nodularity.
The radiographic findings of achalasia include esophageal distention, an esophageal air-
fluid level, aperistalsis, failure of LES relaxation, and retention of barium (Fig. 56.1). The
bird's beak finding is indicative of the narrowing at the gastroesophageal junction.
Administration of a smooth muscle relaxant (e.g., methacholine or nitroglycerin) may
allow the LES to relax and help differentiate between distal esophageal stricture and a
contracted LES. Manometric studies also may be used to confirm the diagnosis in this
complex motility disorder.

FIGURE 56.1. Contrast esophagram demonstrates a
massive dilation associated with achalasia.



Early medical treatment is purely symptomatic and involves encouraging small meals and
using liquids liberally to wash down ingested food. Patients with mild to moderate
dysphagia can be treated with pharmacologic agents designed to decrease LES pressure.
Both calcium channel blockers (e.g., nifedipine) and long-acting nitrates (e.g., isosorbide)
have been used to relieve symptoms and decrease LES pressure (15,16).
Esophagoscopy is recommended for all achalasia patients to determine the presence and
severity of retention esophagitis, to document the functional nature of the obstruction and
to exclude any evidence of malignancy. Achalasia is treated in the early phases with
pneumatic dilation of the LES. Most patients will experience immediate relief from
dysphagia, although symptoms recur in up to 50% over time. The most serious
complication is perforation, which occurs in 1% to 3% of dilations, and appears to be
more likely in patients undergoing their first dilation (17).
Surgery is reserved for patients in whom repeated pneumatic dilations have failed, or if
dilation is deemed to carry increased risk. Contraindications to dilation include a prior
history of esophageal perforation, epiphrenic diverticulum, and adjacent aortic aneurysm.
About 10% to 15% of patients eventually require surgical therapy. The procedure
involves a surgical incision through the muscular layer of the lower esophagus (Heller
myotomy), and can be performed through either open or endoscopic, transabdominal or
transthoracic approaches. The development of reflux is a risk of the procedure, and many
surgeons recommend performing a simultaneous modified fundoplication. A recent study
of 168 patients reported good to excellent relief of dysphagia in 85% of patients
undergoing thoracoscopic myotomy and 93% of patients who underwent laparoscopic
myotomy plus partial fundoplication. The researchers concluded that minimally invasive
surgery, specifically laparoscopic Heller myotomy with partial fundoplication, should be
considered the primary treatment for achalasia (15).
Diffuse Esophageal Spasm
Diffuse esophageal spasm is characterized by dysphagia and pain, although these
symptoms are intermittent and vary in severity. Unlike the symptoms of obstructive
lesions, the dysphagia of diffuse esophageal spasm may be as severe for liquids as for
solids. Exacerbation of symptoms by emotional stress is also common. Diffuse
esophageal spasm is often diagnosed incidentally during routine contrast radiography in a
patient with no esophageal symptoms. Unlike achalasia, there is normal relaxation of the
LES during swallowing.
Barium swallow typically displays a corkscrew-type pattern, although findings vary (Fig.
56.2). These rings of contraction usually affect the lower esophagus but may extend into
the supraaortic region. If the study is performed during a quiescent period, it may appear
normal. If diffuse esophageal spasm is suspected, sequential studies may be necessary to
confirm the diagnosis. One complication of diffuse esophageal spasm is diverticula
formation. These pulsion-type diverticula arise in weak areas of the esophageal muscular
wall.

FIGURE 56.2. Barium esophagram in a patient with
diffuse esophageal spasm.



Endoscopy helps to confirm the diagnosis by documenting nonpropulsive muscular
contractions and should detect evidence of reflux esophagitis and stricture. Manometry
demonstrates the characteristic features of diffuse esophageal spasm: repetitive,
synchronous contractions of relatively high amplitude. These findings are generally seen
in the infraaortic esophagus. High intraluminal pressures are characteristic and are
responsible for the development of diverticula, although normal relaxation of the LES is
usually observed.
The muscular spasms are treated medically with nitroglycerin, calcium channel blockers,
or diazepam, although total elimination of symptoms is seldom achieved. Surgery is
reserved for those with severe, recurrent chest pain, disabling dysphagia or secondary
pulsion diverticula. Transthoracic myotomy is generally regarded as the procedure of
choice for this group of patients, and intraoperative manometry may serve as a useful
adjunct. Debate exists over the necessity of antireflux procedures.
Scleroderma
Scleroderma is a generalized collagen vascular disease in which 80% of patients
eventually develop esophageal symptoms. Typically, scleroderma results in a motility
disorder that causes progressive dysphagia for solids. There appears to be an increased
incidence in those who also manifest the Raynaud phenomenon.
Pathologically, the smooth muscle in the gastrointestinal tract becomes atrophied.
Manometric studies demonstrate diminished contractions in the LES and distal two thirds
of the esophagus. Because the UES is composed of striated muscle, contraction pressures
are usually normal. Although dysphagia occurs, heartburn is the more prominent
symptom because LES tone is attenuated. With compromise of the LES, reflux
esophagitis and its associated complications may develop.
Radiographically, the patient with scleroderma usually has a dilated esophagus with
decreased motility. Unlike achalasia, there is a persistently patent gastroesophageal
junction and no air-fluid level. The radiographic findings of reflux esophagitis are also
commonly observed. Unfortunately, there is little that can be done to treat the disease
process of scleroderma. Therapy is therefore directed toward the resulting GERD.
CRICOPHARYNGEAL DYSFUNCTION
Various terms have been used to describe dysphagia related to dysfunction of the UES,
including cricopharyngeal dysphagia, cricopharyngeal spasm, cricopharyngeal achalasia,
and cricopharyngeal incoordination. Skinner and Belsey offered three categories of
incoordination problems: idiopathic, neurologic, and reflux-induced (18). Whereas the
idiopathic variety is not well understood, neurogenic cricopharyngeal dysfunction may be
secondary to a stroke, cranial nerve palsy (e.g., vagal or glossopharyngeal),
parkinsonism, or other neurologic disease. The most common is cricopharyngeal
incoordination related to GERD.
The patient with cricopharyngeal dysfunction presents with dysphagia that can usually be
localized to the lower neck region. There also may be intermittent symptoms of choking.
Between episodes, the patient may be asymptomatic or may notice a vague throat
discomfort. This condition is often aggravated by stress and may underlie the symptom
complex known as globus sensation. Barium swallow may demonstrate the classic
cricopharyngeal bar with transient partial obstruction (Fig. 56.3), although this finding is
not specific. The underlying problem is usually a lack of coordination between
pharyngeal contraction and cricopharyngeal relaxation, which may be difficult to see on
routine contrast studies.

FIGURE 56.3. Esophagram shows a typical indentation
in the contrast column, indicating a cricopharyngeal bar.



Because the motility problem may be subtle, manometric pressure recordings are the
preferred method of diagnosis. Abnormalities that may be documented with manometry
include weak pressures generated with pharyngeal contraction, a delay in sphincter
relaxation, high resting pressures of the cricopharyngeus (i.e., >50 mm Hg), incomplete
relaxation of the cricopharyngeus, and premature cricopharyngeal contraction (18).
Cricopharyngeal myotomy may be indicated in selected cases of cricopharyngeal
dysfunction, but any associated reflux should be addressed prior to this procedure.
Myotomy is reserved for patients with severe or disabling dysphagia or for those with
aspiration and associated pulmonary problems. Early evidence of diverticular formation
is another indication for cricopharyngeal myotomy. Results vary for myotomy performed
for UES dysfunction related to neurologic abnormalities. If pharyngeal contraction is
impaired, cricopharyngeal myotomy will likely fail to improve swallowing. The efficacy
of botulinum toxin (Botox) in treating this disorder is currently under investigation.
Ahsan et al. described an improvement in swallowing lasting 2 to 14 months in patients
that underwent Botox injection of the cricopharyngeus muscle. Other benefits included a
decrease in aspiration symptoms, removal of tracheotomy, ability to eat solid foods, and
weight gain (19).
ESOPHAGEAL WEBS AND RINGS
Whereas webs are thin membranes consisting of mucosa and submucosa, esophageal
rings are thicker and are composed of mucosa, submucosa, and muscularis. Rings and
webs must be differentiated from benign peptic esophageal strictures, malignant annular
tumors, and muscular contractions. The margins of webs and rings are usually sharp and
thin compared with the longer, tapered margins of benign strictures or the axial
asymmetry and shouldering seen in malignant strictures.
An association of cervical esophageal webs with iron deficiency anemia and glossitis
(Plummer-Vinson syndrome) has been noted, but is extremely rare. Other features
include cheilosis, koilonychia, and splenomegaly. There is also an increased incidence of
carcinoma in the postcricoid and upper esophageal region. Videoradiography is the most
sensitive method available for detection; the web may be missed with conventional
radiography. Treatment consists of endoscopic rupture of the web and iron replacement
for anemia, and typically affords excellent relief of symptoms.
Mid-esophageal and lower esophageal webs may be single or multiple and are treated
with dilation. Lower esophageal webs may be difficult to differentiate from lower
esophageal rings, such as Schatzki's ring, which occurs at the squamocolumnar junction.
It may be asymptomatic or associated with intermittent dysphagia, especially for large or
poorly chewed food boluses. The radiographic picture is typical, with a thin, symmetric,
distal esophageal ring (Fig. 56.4). Asymptomatic rings are identified in 6% to 14% of
barium studies (20). The cause of Schatzki's ring remains unclear, although congenital,
developmental and inflammatory origins have been postulated. Most presenting patients
are over the age of 50. Asymptomatic patients require no treatment, whereas those with
mild dysphagia may benefit from taking care to chew food completely. Patients with
severe or recurrent dysphagia can be treated with dilation, which is generally safe and
highly effective. Rarely, repeat dilations or surgical intervention may be necessary for
refractory symptoms.

FIGURE 56.4. Contrast study shows a smooth, thin shelf
in the lower esophagus (Schatzki's ring).



DIVERTICULA
An esophageal diverticulum is a pouch or sac created by herniation of the lining mucous
membrane through the muscular wall. A true diverticulum exists if all layers of the
esophageal wall are represented within the diverticulum. A false or pseudodiverticulum
consists only of mucosa and submucosa. Typically, diverticula are classified by anatomic
location: pharyngoesophageal, mid-esophageal or mid-thoracic, and epiphrenic. In
addition, they may be categorized by their pathophysiology as pulsion or traction types of
diverticula. Pulsion diverticula are associated with elevated intraluminal pressure,
whereas traction diverticula arise from extraluminal tugging by adjacent sites of
inflammation and fibrosis.
A Zenker diverticulum is a pharyngoesophageal pseudodiverticulum of the pulsion type.
It represents a herniation through a weak area between the inferior pharyngeal constrictor
fibers and the cricopharyngeus muscle. The region of this muscular weakness is known as
a Killian dehiscence or triangle. The mechanism of development for this diverticulum has
been the subject of considerable debate. Hypotheses include increased intraluminal
pressure, increased cricopharyngeal tone, and incoordination of UES contraction and
relaxation.
Zenker diverticula are most often seen in the sixth through ninth decades of life. Men are
affected two to three times more often than women. A history of long-standing dysphagia
with an insidious onset is typical. Retention in the diverticulum may lead to spontaneous
regurgitation and can be accompanied by symptoms of aspiration. With progressive
enlargement, the diverticulum may eventually compress the normal esophageal lumen,
increasing dysphagia and producing symptoms of obstruction. The physical examination
is usually unremarkable, although manual compression of the neck may elicit a gurgling
sensation or crepitus in some patients.
The diagnosis is easily confirmed on barium swallow. Generally, as a Zenker
diverticulum enlarges, it extends inferiorly between the esophagus and vertebral column,
usually on the left (Fig. 56.5). Radiographic defects within the pouch usually represent
retained food material, although tumor is a rarely encountered phenomenon.

FIGURE 56.5. Large, contrast-filled Zenker
diverticulum.



Small, asymptomatic diverticula require no intervention. Numerous surgical options
exist, however, for those requiring treatment due to symptomatic disease. Endoscopic
management of Zenker diverticula has become increasingly popular. The original
technique, known as the Dohlman procedure, required diathermy and a bivalved
esophageal speculum. With one blade in the esophagus and the other in the pouch, the
common wall (which includes the cricopharyngeal muscle) was removed sequentially
with diathermy instruments. A modification of this technique using the microscope and
CO
2
laser was introduced by Van Overbeek, who reported on 544 patients treated
endoscopically with a minimum follow-up of 10 months. There were few complications,
and 99.2% of the patients were highly or fairly satisfied with the results (21). Van
Overbeek found that patients treated with CO
2
laser excision of the diverticulum
experienced less pain and less tendency toward stenosis than patients treated with
electrocoagulation. Other modifications of the Dohlman procedure include flexible
endoscopic techniques and endoscopic staple-assisted diverticulectomy.
Many head and neck surgeons prefer an open, transcervical approach for the treatment of
Zenker diverticula (Fig. 56.6). Packing the diverticulum endoscopically with gauze is
beneficial in identifying the pouch at surgery. Small diverticula (< 2 cm) can be managed
adequately with cricopharyngeal myotomy alone, minimizing postoperative
complications and morbidity. The muscular incision should be placed in the posterior
midline to avoid recurrent laryngeal nerve injury. Larger diverticula require removal in
combination with myotomy. Complications of surgery include hematoma, wound
infection, leakage, fistula, mediastinitis and recurrent laryngeal nerve injury. Stenosis and
recurrent diverticula also may occur. Diverticulopexy may be preferable in elderly
patients for whom a more extensive procedure would significantly increase operative
risk. With the patient under local anesthesia, the sac can be identified and tacked up to
the prevertebral fascia, preventing retention of food products and the associated sequelae.

FIGURE 56.6. Transcervical diverticulectomy. A: Skin
incision. B,C: Exposure of the pharynx and cervical
esophagus. D,E: Dissection of the diverticulum with
myotomy. F: Excision. G: Closure of the cervical
esophagus. H: In selected cases, the diverticulum may be
inverted and sutured to the prevertebral fascia
(diverticulopexy).



Mid-esophageal diverticula are traction diverticula associated with inflammatory
processes in the parabronchial region. These are true diverticula and typically are small
and asymptomatic. Associated complications include diverticulitis, perforation, bleeding,
and fistula formation. Barium swallow demonstrates a wide-mouthed diverticulum in the
mid-portion of the esophagus. Surgery is reserved for patients with complications and
consists of a right thoracotomy with excision of the diverticulum.
Epiphrenic diverticula represent an uncommon type of pulsion diverticula that arise from
the lower esophagus, usually in the most distal 5- to 10-cm segment. They usually arise
proximal to a mechanical or functional obstruction. They range in size from less than 1
cm to greater than 10 cm. There is a frequent association with other conditions, including
hiatal hernia with reflux esophagitis, diffuse esophageal spasm, achalasia, and carcinoma
of the esophagus. Some researchers suggest that an area of congenital weakness exists in
the wall of the distal esophagus, which produces outpouching in response to prolonged
increases in intraluminal pressure. The predominant symptoms are dysphagia and
regurgitation, although obstruction may occur with large diverticula. Endoscopy may be
helpful in evaluating associated conditions, but must be performed with extreme caution
to prevent perforation of the thin-walled diverticulum. In symptomatic patients, surgery
consists of diverticulectomy and correction of any underlying esophageal disorder.
INFECTIOUS AND INFLAMMATORY CONDITIONS
Esophagitis can be caused by many physical, chemical, and infectious agents. The most
common cause of esophagitis, as previously discussed, is GERD. In patients with
immunosuppression from disease or medications, opportunistic infection may occur.
Candida albicans is the most common organism infecting the esophagus. In the early
stages, small plaquelike filling defects in the mucosa are seen on contrast radiography. In
more advanced cases, a shaggy, cobblestone appearance is seen. The most common
symptoms are odynophagia and dysphagia, and oral thrush is present in approximately
75% of cases. When candidal esophagitis is encountered, the possibility of human
immunodeficiency virus (HIV) infection must be considered. Although topical (nystatin)
and oral agents (fluconazole, ketoconazole) are generally successful in immunocompetent
patients, systemic antifungal agents such as intravenous fluconazole or amphotericin B
may be necessary to eradicate the disease in the immunocompromised. Herpes
esophagitis is seen less commonly, but also occurs in immunosuppressed patients.
Clinical symptoms and radiologic findings are similar to candidiasis. Multiple, discrete
mucosal ulcers on air-contrast esophagrams are characteristic of viral esophagitis.
Cytologic examination of endoscopic brush or biopsy specimens demonstrates
multinucleated cells containing intranuclear inclusion bodies.
Radiation esophagitis occurs rarely in patients undergoing cervical or mediastinal
irradiation. Typically, motor dysfunction exists without mucosal abnormalities, but
diffuse ulceration can be seen in some patients acutely. Smooth tapered strictures may
develop as a late complication.
Medications can cause a localized esophagitis if the contact time with esophageal mucosa
is sufficient. Drug-induced esophagitis is seen more commonly in patients ingesting
tablets at bedtime. Any underlying problems causing a functional obstruction may further
prolong drug-mucosal contact. The medications most often responsible are tetracycline,
doxycycline, quinidine, and potassium. A localized ulceration in the mid-esophagus is the
most common finding in these cases.
Bullous dermatoses may affect the esophagus. This group of diseases includes
pemphigoid, epidermolysis bullosa, toxic epidermal necrolysis, and Stevens-Johnson
syndrome. Pemphigoid is a chronic blistering disease involving mucosal epithelium,
which affects the esophagus in 5% of patients. Patients who have this disease and
complain of dysphagia should be further studied radiologically. Radiologic findings vary
with the stage of disease and may include mucosal edema, spasm, adhesions, webs, and
strictures usually involving the cervical esophagus. Even total occlusion has been
reported from these ruptured blebs and resultant adhesions. Histologically, pemphigoid is
characterized by subepithelial clefting and a linear pattern of direct immunoglobulin G
immunofluorescence at the basement membrane. Epidermolysis bullosa comprises a
group of hereditary skin disorders in which there is a loss of cohesion between the
epidermis and dermis. This results in blister formation, ulceration and scarring of the skin
and mucosal surfaces. Esophageal involvement is seen in patients with epidermolysis
bullosa dystrophica. The radiographic findings include small nodular filling defects (i.e.,
bullae), ulcerations, spasm, dysfunctional motility, webs, and strictures. Esophagoscopy
and bougienage should be withheld unless absolutely necessary because the instruments
may further aggravate or initiate bullae and ulcerations.
BENIGN NEOPLASMS AND CYSTS
Benign tumors and cysts of the esophagus are relatively rare, occurring less frequently
than malignant tumors. Esophageal lesions can be classified as intraluminal, intramural,
or extramural. Intramural tumors are usually asymptomatic until they become
significantly enlarged. Because they are mucosally covered, it is uncommon for these
tumors to be associated with ulceration and bleeding. Leiomyoma is the most common
benign tumor of the esophagus, representing an intramural tumor arising from the
muscularis mucosa (Fig. 56.7). In 90% of patients, it occurs in the middle or lower third
of the esophagus. Patients usually present with dysphagia, although many leiomyomas
are found radiographically in asymptomatic patients. These tumors are usually single but
may be multiple. Generally benign, they may be confused histologically with
leiomyosarcoma. Surgical excision is reserved for symptomatic patients or those in whom
histologic confirmation is advisable. The tumors are well encapsulated and have a low
rate of recurrence after thoracotomy and enucleation. Less frequent intramural tumors
include myomas, fibromas, lipomas, neurofibromas, and granular cell tumors. Benign
cysts of the esophagus may be intramural or extramural.

FIGURE 56.7. This smooth, well-demarcated, intramural
mass of the esophagus is a leiomyoma.



Polyps are the most common intraluminal lesions, although papillomas, adenomas, and
hemangiomas may occur. Fibrovascular polyps can grow to an enormous size and have
been reported to prolapse into the hypopharynx, causing asphyxiation and death. Most
polyps occur in the cervical esophagus, causing dysphagia and regurgitation. Barium
swallow demonstrates an intraluminal, pedunculated mass. Most can be excised
endoscopically by snaring the base of the polyp.
ESOPHAGEAL CARCINOMA
Esophageal carcinoma accounts for approximately 1% of all new cancers. Epidemiologic
studies have shown an increased incidence among patients with a history of heavy
tobacco and alcohol consumption. Other risk factors include caustic injury or esophageal
stasis, as seen in patients with Plummer-Vinson disease or esophageal webs. Some
investigators report a dramatic increase in esophageal cancer among patients with
achalasia, although others have failed to find an association. Adenocarcinoma is known
to develop in as many as 15% of patients with Barrett's esophagus. The most common
symptoms in patients with an esophageal malignancy are painless dysphagia and weight
loss. Other symptoms or findings may include odynophagia, dysphagia, anemia,
hemorrhage, aspiration pneumonia, vocal cord paralysis or cervical adenopathy.
Unfortunately, esophageal cancers may be relatively advanced by the time symptoms
occur, contributing to an overall 3-year survival rate of only 11% (22).
The predominant neoplasm of the esophagus is squamous cell carcinoma. In a review of
7,000 cases, tumors originated in the upper third of the esophagus in 17%, middle third in
47%, and lower third in 36% (23). Endoscopically, a squamous cell carcinoma of the
esophagus may appear ulcerative, exophytic, or superficial and plaquelike. Tumor spread
may occur directly or via intraluminal, lymphatic, or hematogenous routes. Because the
esophagus lacks an outer serosal barrier, early transmural extension into adjacent
structures can occur.
Adenocarcinoma is found far less frequently than squamous cell carcinoma, occurring
primarily in the distal esophagus. If the lower third is excluded, adenocarcinoma accounts
for fewer than 5% of esophageal malignancies (23). Three histologic sites of origin have
been suggested, including the esophageal mucosal or submucosal glands, heterotopic
gastric mucosa, and metaplastic gastric mucosa of Barrett's esophagus.
Barrett's esophagus is the primary recognized risk factor for adenocarcinoma of the
esophagus. Most centers recommend regular endoscopic surveillance, with mucosal
biopsies, for dysplasia and aggressive treatment of any accompanying GERD. The
associated dysplastic changes are classified as low grade or high grade based on nuclear
morphology and glandular architecture. Low-grade lesions are treated with antireflux
therapy and routine endoscopic examination to detect any progression of disease. For
high-grade lesions, felt to represent early adenocarcinoma, surgery is advised to resect
that portion of the esophagus lined by columnar epithelium (24).
The diagnostic evaluation of esophageal cancer includes chest radiography,
esophagography, esophagoscopy with brush cytology or biopsy, endoscopic
ultrasonography, and CT scans of the chest and abdomen. Esophagograms are highly
sensitive in detecting and defining esophageal malignancies but still have a false-negative
rate of about 5%. Esophagoscopy can be used to identify the site and extent of a lesion
and to obtain tissue for histologic diagnosis.
Accurate preoperative assessment of local tumor infiltration is essential because tumors
limited to the epithelium and lamina propria of the mucosa have not been associated with
lymph node metastasis, whereas spread to regional lymph nodes is seen in 50% of
patients with infiltration of the submucosa (25). CT scanning can provide information
about extraesophageal infiltration and metastasis. Some centers also advocate
laparoscopy for preoperative staging.
The treatment of esophageal carcinoma continues to evolve. Most studies recommend a
stage-related concept of surgical treatment, often combined with radiotherapy or
chemotherapy. There is increasing interest in the combined use of chemotherapy and
irradiation. In one series, 1- and 2-year cumulative survival rates were doubled, and better
palliation achieved, using chemoradiation instead of irradiation alone (26). Other studies
have found that, compared with surgery, chemoradiation results in comparable survival
for T1 (tumor invasion of the lamina propria or submucosa) and T2 (tumor invasion of
the muscularis propria) esophageal carcinomas (27).
Surgery remains the treatment of choice, however, for tumors deemed resectable,
depending on the patient's risk for perioperative morbidity or mortality. Tumors limited
to the epithelium and lamina propria may be treated with minimally invasive techniques
such as endoscopic resection, endoscopic laser photocoagulation, or thoracoscopic
resection. Surgical approaches to more advanced disease involve transthoracic
esophagectomy with gastric pull-up or esophagogastrectomy, depending on the location
and extent of the tumor. Preoperative, neoadjuvant treatment with chemoradiation is also
under investigation and, in some series, has appeared to enhance survival (28).
COMPLICATIONS AND EMERGENCIES
The complications and emergencies associated with esophageal disease are presented in
Table 56.7 and Table 56.8, respectively. Several of the complications described are risks
of the various endoscopic and surgical treatments of these disorders.

TABLE 56.7. COMPLICATIONS
ESOPHAGEAL DISORDERS



TABLE 56.8. EMERGENCIES ESOPHAGEAL
DISORDERS



Perforation and Rupture
Esophageal tears and perforations can result from blunt or penetrating trauma, from
neoplastic or long-standing inflammatory disease, or from injury during rigid or flexible
esophagoscopy, or they may arise spontaneously. The clinical presentation of a patient
with esophageal perforation depends on the site and cause of the injury and the length of
time from perforation to diagnosis. Leakage of saliva, gastric acid, and bile initially
creates a chemical inflammation, usually in the mediastinum or pleura. As bacterial
contamination occurs, these events may lead to the rapid development of mediastinitis
and sepsis. In patients at risk for esophageal perforation, complaints of chest or
abdominal pain, dysphagia, odynophagia, or shortness of breath should be further
evaluated. Subcutaneous emphysema may be present in the neck, and mediastinal
emphysema may manifest as a crunching sound on auscultation (i.e., the Hamman sign).
Other physical findings include fever, tachypnea, and tachycardia. A chest radiograph or
CT scan may demonstrate pneumomediastinum or pneumothorax, or an inflammatory
process or abscess.
The most common cause of esophageal perforation is surgical instrumentation.
Endoscopic procedures are the leading causes of these injuries, with an incidence of
iatrogenic perforation of 0.1% to 1.5% (29). The most common site of perforation during
endoscopy is through the posterior wall of the cervical esophagus. Other common sites
include the narrowing at the level of the aortic arch and the gastroesophageal junction.
Spontaneous esophageal injuries occur in Mallory-Weiss syndrome and Boerhaave
syndrome. In Mallory-Weiss syndrome, the patient usually presents with upper
gastrointestinal bleeding after vomiting, retching, or coughing. Increased intraabdominal
pressure causes a nonpenetrating mucosal tear in the lower esophagus or cardia of the
stomach. This tear is associated with a laceration of the submucosal arteries and may
result in intermittent bleeding or massive hemorrhage. In 50% of cases, hypovolemic
shock occurs and the first step in treatment is adequate fluid resuscitation and transfusion
if necessary. In most patients, spontaneous cessation of bleeding occurs. The diagnosis is
confirmed endoscopically, revealing a linear, mucosal laceration of the distal esophagus
or just below the gastroesophageal junction. In patients with persistent bleeding,
endoscopic treatment with epinephrine injection (1:10,000) or electrocoagulation of the
bleeding site is generally effective. Operative intervention may be required for massive
bleeding and consists of gastrotomy with oversewing of the tear.
Boerhaave syndrome is characterized by a spontaneous rupture of the esophagus.
Precipitating events include vomiting, vigorous coughing, weight lifting, and straining.
Esophageal rupture also has been reported in the setting of esophagitis and distal
esophageal obstruction. Boerhaave syndrome is usually associated with a left-sided,
transmural rupture of the distal esophagus. Chest radiography will demonstrate
mediastinal widening and pneumomediastinum. A pneumothorax or pleural effusion also
may be seen. Symptoms include severe substernal or epigastric pain, pleuritic chest pain,
dyspnea, fever, and cervical crepitus. A water-soluble contrast esophagogram confirms
the diagnosis (Fig. 56.8).

FIGURE 56.8. Findings in a patient with Boerhaave
syndrome, demonstrating a perforation and leak in the
lower esophagus.



The differential diagnosis for esophageal perforation should include perforated peptic
ulcer and acute myocardial infarction due to their similarities in presentation. Although
difficult, prompt diagnosis of an esophageal perforation is crucial because operative risks
increase significantly after the first 24 hours. In one series, the correct diagnosis was
reached within the first 12 hours in only 21% of patients. Surgical therapy includes
drainage of the mediastinum and pleura, elimination of the source of contamination, and
appropriate nutritional support. Thoracotomy or transcervical exploration may be
indicated for adequate surgical drainage, and in many cases the esophageal tear can be
identified and repaired during the operation.
Hemorrhage
Esophageal hemorrhage may arise from different disease states. An esophageal
diverticulum can become inflamed and ulcerate or perforate, causing hemorrhage. Long-
standing peptic strictures can ulcerate and may result in significant bleeding. Malignant
disease may cause bleeding from erosion into major vessels, leading to massive or lethal
hemorrhage. A Mallory-Weiss tear may result in spontaneous hemorrhage as described
above. Iatrogenic hemorrhage is a rare, but possible, complication of endoscopy or
endoscopic therapies. Esophageal varices may develop in patients with underlying portal
hypertension and are also associated with massive, sometimes uncontrollable,
hemorrhage. Appropriate candidates can be treated with endoscopic sclerotherapy or
banding or the varices. In difficult cases, a Sengstaken-Blakemore tube is sometimes used
to tamponade the bleeding.
Mediastinitis
Mediastinitis results after contamination of the mediastinal tissue by means of esophageal
perforation and leakage. Minor tears often seal spontaneously without significant
mediastinal infection. More serious perforations, however, are associated with continued
leakage, resulting in a mediastinal inflammatory response and infection. Unfortunately,
the early diagnosis of esophageal perforation is difficult due to delay in the development
of associated symptoms.
Obstruction
Esophageal obstruction is often preceded by a long history of dysphagia. Acute
obstruction without prior history of dysphagia suggests the presence of a foreign body. A
foreign body may be radiopaque or radiolucent, depending on its makeup, and the
diagnosis may depend heavily on the patient's history. After removal of a foreign body,
careful endoscopic examination is necessary to rule out an underlying web, stricture, or
neoplasm.
Obstruction can occur as an exacerbation of achalasia or may represent luminal
obstruction by intrinsic or extrinsic neoplastic disease. Chronic reflux esophagitis can
lead to peptic stricture formation, ultimately producing an obstruction.
The treatment of esophageal obstruction depends on its cause. Benign tumors, polyps, or
diverticula can be removed surgically. Bougienage or pneumatic dilatation can be used
for webs, rings, strictures, or severe achalasia. Even benign disease processes such as
peptic stricture can be recalcitrant, however, and may eventually require esophagectomy
and reconstruction with gastric pull-up, colon interposition, or microvascular free tissue
transfer. In some circumstances, a gastrostomy or jejunostomy for long-term nutrition
may be appropriate. Esophageal malignancies are treated as described above with
appropriate combinations of surgery, radiation therapy, and chemotherapy.
The major emergencies related to the esophagus include hemorrhage, perforation,
obstruction, and caustic ingestion. Table 56.8 summarizes the management of these
emergencies. The diagnosis and treatment of caustic ingestion is covered in greater detail
in Chapter 76.

HIGHLIGHTS
The most common esophageal problem is gastroesophageal
reflux. The major mechanisms involved include competence of
the LES, esophageal clearance, gastric volume and emptying,
and tissue resistance.
Gastroesophageal reflux disease is treated with life-style and
dietary modification, H
2
receptor antagonists, proton pump
inhibitors, and surgical antireflux procedures.
Gastroesophageal reflux disease may be complicated by
extraesophageal manifestations including LPR. Patients may
present with chronic cough, throat irritation, laryngeal contact
ulcers, symptoms of aspiration, and other complaints. Flexible
fiberoptic laryngoscopy and 24-hour pH monitoring can be
helpful in making the diagnosis.
The hallmarks of achalasia are aperistalsis, esophageal
dilatation, and failure of the LES to relax.
Esophageal webs and rings usually appear as areas of
narrowing on contrast studies, typically with sharp, thin
contours. They are usually successfully treated with esophageal
dilation.
Cricopharyngeal dysfunction may be linked to an underlying
disorder or may be idiopathic. Manometric findings at the UES
include delay in relaxation, high resting pressures, incomplete
relaxation, or premature contraction.
Zenker diverticulum is generally associated with
cricopharyngeal dysfunction. Treatment options include
observation, endoscopic treatment, open diverticulectomy with
cricopharyngeal myotomy, cricopharyngeal myotomy alone, or
diverticulopexy.
Esophageal carcinoma remains a lethal malignancy, partly due
to its typically advanced stage at the time of presentation.
Awareness of the signs and symptoms associated with
esophageal perforation is important, because prompt treatment
is indicated.
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6. Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a
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9. Zeitoun P, Rampal P, Barbier P, et al. Omeprazole versus ranitidine in the treatment of reflux
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gastroesophageal reflux. J Pediatr Gastroenterol Nutr 1999;28:518528.
11. Spechler SJ. Comparison of medical and surgical therapy for complicated gastroesophageal reflux
disease in veterans. N Engl J Med 1992;326:786792.
12. Jones R, Canal D, Inman M, et al. Laparoscopic fundoplication: a three-year review. Am Surg
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13. Harrill WC, Stasney CR, Donovan DT. Laryngopharyngeal reflux: a possible risk factor in
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15. Patti MG, Pellegrini CA, Horgan S, et al. Minimally invasive surgery for achalasia: an 8-year
experience with 168 patients. Ann Surg 1999;230:587594.
16. Traube M, Dubovik S, Lange RC, et al. The role of nifedipine therapy in achalasia: results of a
randomized, double-blind, placebo-controlled study. Am J Gastroenterol 1989;84:1259.
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Management of esophageal disease. Philadelphia: WB Saunders, 1988:431.
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20. Hill LD, Mercer CD. Rings, webs, and diverticula. In: Hill L, Kozarek R, McCallum R, et al., eds.
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21. Van Overbeek JJ. Meditation on the pathogenesis of hypopharyngeal (Zenker's) diverticulum and
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26. Madhu JJ, Flam MS, Mowry PA, et al. Radiotherapy alone and chemoradiation for nonmetastatic
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

57 COMPLEX UPPER AIRWAY PROBLEMS
Head & Neck SurgeryOtolaryngology
57




COMPLEX UPPER AIRWAY PROBLEMS
ROBERT A. SOFFERMAN

R.A. Sofferman: Division of OtolaryngologyHead and Neck Surgery, University of Vermont School of
Medicine, and Fletcher Allen Health Care, Burlington, Vermont.

Methods
Case Report
Results
Summary
Chapter References
Assessment and management of a tenuous airway must be performed with general
anesthesia regardless of the age of the patient. The usual orderly procession from mask
preoxygenation through parenteral sedation and final endotracheal intubation is altered in
many ways. The patient may arrive in the operating suite in an acute airway emergency
or in an elective circumstance with potential evolving pitfalls and dangers. Lowering
patient risks to the absolute minimum necessitates standardization of basic maneuvers
and a team approach with open dialogue among surgeon, anesthesiologist, and nursing
staff.
Each airway problem has its own special causes and nuances. The following general
considerations are critical to proper direction of care: (a) whether the patient has an
empty or full stomach, (b) whether the patient is an adult, a child, or an infant, (c)
underlying cardiorespiratory status and time or margin of relative hypoxia, (d) tolerance
of the supine position, (e) status of the cervical spine, (f) stability of the mandible, (g)
oropharyngeal patency, (h) presence of oropharyngeal bleeding, (i) level of patient
anxiety, and (j) severity of obstruction. The locus of airway obstruction and the cause of
the obstruction may necessitate vastly different intubation considerations. Each of these
conditions can alter the basic path toward securing the airway. The availability of several
technologic options within a reasonably practical limit should maximize patient safety.
Many patients with a marginal airway arrive in the operating room with an augmented
level of apprehension. During the securing of monitoring devices, discussions with staff
such as residents and surgeon, and placement of the face mask, the anesthesiologist may
notice a high level of anxiety. Sometimes a limited infusion of sedative improves the
situation, but often these agents are withheld or contraindicated. The all too familiar
progressive upper airway obstruction amplified by a semirecumbent or supine position
can cause a rapid sequence of emergency events. Numerous attempts at intubation in a
setting with suboptimal visualization or emergency tracheotomy or cricothyrotomy may
be the only possible maneuver.
METHODS
Several technologic advances allow airway management teams to avoid desperate
conditions or at least provide more alternatives. As with any dangerous situation,
prevention must be the first axiom. The anesthesiologist can reduce the likelihood of
precipitating airway decompensation through the technique of awake intubation over a
flexible bronchoscope (1). This is the most common nonsurgical method of gaining entry
to the airway when mandibular excursion is limited or there is uncertainty concerning the
anatomic features of the larynx and access. Despite the assumed safety of this method,
airway decompensation can evolve. The flexible bronchoscope is vulnerable to visual
occlusion from saliva or blood, and manipulation techniques require expertise even in the
simpler elective setting. Alternatives to flexible endoscopy other than surgical entrance to
the airway increase the safety margin.
The purpose of this chapter is to introduce three devices that can be used in secondary
measures in the management of a problem airway. The gum elastic bougie introducer,
laryngeal mask airway (LMA), and esophagotracheal combination tube (ETC) may not
be familiar to otolaryngologisthead and neck surgeons. Anesthesiologists and critical
care specialists have a working knowledge of one, two, or all of the devices, and it may
seem that the surgeon should be excluded from use of these systems. However, the lost
airway becomes a shared problem that necessitates the cooperation and trust between the
anesthesiologist and the surgeon. If the surgeon understands the technology, observes its
practical application, and trusts it to preserve the airway with speed and efficiency,
emergency tracheotomy or cricothyrotomy may not be the first thought in desperate
circumstances. The stylet systems often require the active participation of the surgeon
and use of endoscopic techniques familiar only to surgeons.
The gum bougie introducer (2) is an excellent first line of emergency management of a
lost airway (Fig. 57.1). It is the essence of simplicity and functions best in conjunction
with a closed anterior commissure laryngoscope commonly used for direct laryngoscopy
(Fig. 57.2). In many circumstances, even the most experienced anesthesiologist cannot
visualize a compromised larynx while using a blade laryngoscope. An experienced
surgeon usually can advance a Holinger anterior commissure laryngoscope at least to the
posterior glottis and use it as a guide to orotracheal intubation. This laryngoscope has
better leverage capabilities than a blade laryngoscope. Adequate length, recessed lighting,
anterior flare at the distal oval end, and option for concurrent rigid microsuction during
laryngoscopy make this instrument a superior adaptation for bypassing friable obstructing
tumors (Fig. 57.3). Perhaps the greatest advantage of the anterior commissure
laryngoscope over the Miller or Macintosh blade of an anesthesiologist's laryngoscope is
the opportunity to approach the endolarynx from a low profile. When mandibular
excursion is limited, the upper dentition unusually long and difficult to negotiate, or the
larynx in an exaggerated anterior position, an anterior commissure laryngoscope can be
inserted and advanced from an extreme posterior direction. It is possible to insert the
laryngoscope in a position posterior to the last mandibular and maxillary molars and gain
a more direct approach to the difficult larynx.

FIGURE 57.1. Gum elastic bougie introducer compared
with endotracheal tube advanced over a guide.



FIGURE 57.2. Gum elastic bougie introducer inserted
into the larynx and trachea through a Holinger
laryngoscope. (From Sofferman RA, Johnson DL,
Spencer RF. Lost airway during anesthesia induction:
alternatives for management. Laryngoscope
1997;107:14761482, with permission.)



FIGURE 57.3. A: Anterior commissure laryngoscope
with anterior flare or tip. B: Narrow oval distal aperture
with recessed light channel. (From Sofferman RA,
Johnson DL, Spencer RF. Lost airway during anesthesia
induction: alternatives for management. Laryngoscope
1997;107:14761482, with permission.)



The gum bougie must be long and be well outside the oral cavity so that an endotracheal
tube can be passed over it while the external tip is held in the fingers. The bougie must be
semirigid to hold its shape and large enough in diameter to prevent buckling. The bougies
are refrigerated until used to prevent them from becoming too flexible during insertion,
but the cold rigidity usually lasts for a sufficient time. The ends are rounded and smooth,
but the device must be lubricated for ease of slide of the endotracheal tube. A small
polyvinyl chloride endotracheal tube can pass over an average bougie (Fig. 57.4). A
variety of bougie sizes are available. The most critical requirement for use of this
intubation technique is careful planning between anesthesiologist and surgeon before the
airway is manipulated in any way. As with all of these methods, every critical piece of
equipment must be in the operating room, operational, and at arm's length. The method of
intubation must be ego-exclusive with a planned preintubation arrangement concerning
when the bougie technique is to be used. In essence, this technique becomes the
otolaryngologisthead and neck surgeon's substitute for a surgical airway.

FIGURE 57.4. Endotracheal tube advanced over bougie
guide. The mandible is pulled forward manually or with a
Macintosh blade laryngoscope. (From Sofferman RA,
Johnson DL, Spencer RF. Lost airway during anesthesia
induction: alternatives for management. Laryngoscope
1997;107:14761482, with permission.)



A hollow jet stylet introducer (3) with capnography has been tested and used clinically in
40 intubations at the University of Vermont (4). It represents a marriage of the technique
of gum bougieguided intubation and capnography. Instead of a solid guide, a hollow
tube with stylet is inserted into the trachea, and segmental end tidal carbon dioxide
measurements are rapidly obtained. Esophageal placement is confirmed with the presence
of flat-line carbon dioxide waveforms. Proper tracheal insertion is confirmed with the
presence of ventilatory (sinusoidal) carbon dioxide waveforms of greater than 20 mm Hg
on a capnograph. With confidence that the introducer is properly situated in the airway,
intubation over the guide can take place. The principal advantage of this technique is the
ability to use jet ventilation through the introducer once carbon dioxide waveforms have
been found. In truly marginal circumstances in which hypoxia has been extended to the
absolute limits of safety, initiating oxygenation with jet before tube insertion can be an
important option. Exchange catheters can afford ventilation options, but the extreme
flexibility and tendency to buckle make them less suitable for use in desperate airway
circumstances. A helpful modification allows ideal initial ventilation options and a rigid
guide over which the endotracheal tube can be advanced into the larynx and trachea (Fig.
57.5). The brass insert into the lumen of the exchange catheter allows configuration of a
rigid but semimalleable stylet. This modification has all of the advantages of the gum
bougie introducer and adds the capability of jet ventilation and oxygenation.

FIGURE 57.5. The jet ventilation stylet is a modified
exchange catheter with a brass insert. The sequence
shows that the catheter has calibration marks to monitor
depth of insertion. Oxygenation can be maintained during
preparation for advancement of the endotracheal tube.



The LMA and the ETC represent two ends of a spectrum of extratracheal ventilation. The
LMA was first tested in England in 1983, became commercially available there in 1988,
and currently is used as the preferred ventilation technique in one half of surgical
procedures requiring general anesthesia (5,6). It was approved for use in the United
States in 1991. The LMA is used principally by anesthesiologists in the operating room
for both elective surgery and as a means of managing a problem airway. The ETC is an
emergency tool used most often during resuscitation (7). It can be inserted by a critical
care specialist, skilled nurse, or emergency care physician in a blind ventilation
technique.
The LMA (8) is a clever hybrid of the characteristics of an endotracheal tube and silicone
face mask (Fig. 57.6). The mask portion is triangular (Fig. 57.7) and can easily be
inserted blindly into the hypopharynx. It is constructed so that as the mask is inflated it
gently distends to fill the hypopharynx and cover the laryngeal introitus (Fig. 57.8). The
tip rests in the esophageal inlet, and the unit does not pass into the esophagus because of
its size. Insertion is simple and does not require direct airway visualization. Correct
placement of the mask is accomplished for nearly 90% of patients on the first attempt
(9,10). The open slit aperture within the mask allows direct inspection of the internal
larynx with a flexible bronchoscope or passage of a hollow jet introducer. The
endotracheal tube can be inserted through the mask or over a guide (Fig. 57.9). The LMA
may not perform well when a bulky obstructing tumor limits the patient's ability to
breathe or when secretions are so profuse that the larynx must be bypassed. Nevertheless,
an LMA is a fast and simple option when all else is failing.

FIGURE 57.6. Laryngeal mask airway with inflatable
laryngeal cover mask.



FIGURE 57.7. Internal view of the laryngeal mask
airway. (From Sofferman RA, Johnson DL, Spencer RF.
Lost airway during anesthesia induction: alternatives for
management. Laryngoscope 1997;107:14761482, with
permission.)



FIGURE 57.8. Laryngeal mask airway in position in a
sagittal model. (From Sofferman RA, Johnson DL,
Spencer RF. Lost airway during anesthesia induction:
alternatives for management. Laryngoscope
1997;107:14761482, with permission.)



FIGURE 57.9. Endotracheal tube intubated through a
laryngeal mask airway but over the bougie guide.



The ETC is a twin-lumen tube with an open tracheal cannula and a blocked distal
esophageal end (Fig. 57.10). The device is inserted blindly, and the upper and lower
elastic balloons are inflated (11). The esophagus and oropharynx are completely
obliterated to allow ventilation perforations between the two obturator balloons to
ventilate the trachea. With blind insertion, the tip of the ETC usually finds its way into
the esophagus, and ventilation is accomplished through the esophageal port. If the trachea
has been intubated during blind insertion, ventilation is accomplished conventionally
through the tracheal port. The esophageal port is then ignored. The predecessor of the
ETC, the esophageal obturator airway, is considerably longer. The disadvantages of the
esophageal obturator airway are its length, requirement for a face-mask seal, association
with esophageal and gastric rupture, and risk of airway obstruction in accidental tracheal
intubation (7). The ETC is mentioned in the guidelines for advanced cardiac life support
of the American Heart Association (12) and practice parameter on guidelines for
management of the difficult airway of the American Society of Anesthesiologists (13).
Use of an ETC is recommended in the care of patients with expanding hematoma (14),
bull neck syndrome and failed intubation (15), impalement neck trauma (16), and
oropharyngeal bleeding during thrombolytic therapy (17), all of which obscure laryngeal
visualization.

FIGURE 57.10. Esophagotracheal combination tube in
the esophageal position. The esophageal channel (no. 1)
and tracheal cannula (no. 2) are color coded. Each
balloon has printed on its external syringe adapter a
recommended volume of air to be instilled (15-cc distal
balloon, 100-cc proximal pharyngeal balloon). (From
Sofferman RA, Johnson DL, Spencer RF. Lost airway
during anesthesia induction: alternatives for management.
Laryngoscope 1997;107:14761482, with permission.)



In a controlled study involving 37 patients, investigators compared the time of insertion
and establishment of proper airway ventilation between intensive care unit nurses using
the ETC and trained emergency physicians using conventional orotracheal intubation
(18). The average time for ETC insertion was shorter than endotracheal intubation (18.5
versus 27.2 seconds), and the difference was statistically significant. The ETC should not
be used in the treatment of patients with an intact gag reflex, children and patients
younger than 16 years, or patients with proximal esophageal disease (14). An additional
theoretic problem is obstructing laryngeal or hypopharyngeal tumor when ventilation
through the obstructed glottis has not been accomplished even though the problem of
poor visualization has been circumvented. The ETC still is used principally in emergency
departments and intensive care units and thus remains foreign to both anesthesiologists
and otolaryngologisthead and neck surgeons. A 1994 report from Austria (19)
introduced the ETC to the otolaryngologic literature for use in elective tracheotomy. Six
patients in an intensive care unit with respiratory insufficiency and prolonged intubation
underwent tracheotomy over an ETC. In those authors' experience, no cases of
esophageal or gastric rupture occurred in more than 500 insertions.
CASE REPORT
An instructive review of management of an actual complex airway shows the efficacy of
the LMA as a life-saving last resort after trial and failure of several conventional
methods. The patient, a 33-year-old woman, needed surgical treatment of upper and
lower airway obstruction from proliferative tongue-based lymphoid hyperplasia and
massive substernal goiter. Symptoms of episodic choking, obstructive sleep apnea, stridor
at rest, and inability to lie supine demanded corrective surgery. Carefully planned
thyroidectomy and laser ablation of lymphoid tissue were discussed with the anesthesia
staff. The patient was judged a poor anesthesia risk because of exogenous obesity, a short
bull neck, and the aforementioned clinical circumstances. Awake flexible bronchoscopic
intubation was planned with the knowledge that a surgical airway would not be a reliable
primary or secondary option because of the obstructing goiter (Fig. 57.11).

FIGURE 57.11. A (axial CT scan, lower cervical
region), B(axial CT scan, anterior mediastinum): Large
goiter over trachea and filling upper mediastinum
precludes tracheotomy or cricothyrotomy. (From
Sofferman RA, Johnson DL, Spencer RF. Lost airway
during anesthesia induction: alternatives for management.
Laryngoscope 1997;107:14761482, with permission.)



During methodical bronchoscopy the airway became obstructed, ventilation could not be
performed, and several vain attempts at intubation were made. As cyanosis and
bradycardia developed, one attempt at rigid bronchoscopy with a Miller blade
laryngoscope also failed to visualize the larynx and secure the airway. In desperation, a
no. 4 LMA was inserted by the anesthesiologist and effectively produced ventilation and
good oxygen saturation. A 6.5-mm cuffed endotracheal tube was inserted through the
LMA, and proper insertion was confirmed with flexible bronchoscopy and end tidal
carbon dioxide measurement. The LMAendotracheal tube unit was left in place
throughout the operation. Subtotal thyroidectomy and tracheotomy were performed, and a
secondary procedure planned for 4 weeks later to address the lymphoid hyperplasia.
Results of a histopathologic examination confirmed a mixture of lymphoid hyperplasia
and squamous papillomatosis. During subsequent laser oblation, 3 hours of meticulous
laser vaporization of the obstructing tissue were needed before the endolarynx could be
visualized. The patient maintained the tracheotomy tube and needed several
endobronchial laser treatments of newly developed subglottic and tracheal
papillomatosis.
RESULTS
Several patients with difficult airway visualization or decompensation during induction
have been treated preferentially with a jet ventilation stylet inserted through a Holinger
anterior commissure laryngoscope and subsequent intubation over the stylet. In these
cases, tracheotomy under local anesthesia would have been the preferred option of the
anesthesia staff, but in each circumstance the patient's stridor and anxiety in the supine
position virtually guaranteed airway decompensation during the procedure. Mask
ventilation, parenteral sedation, and one failed attempt at conventional orotracheal
intubation by the anesthesiologist were followed rapidly by the anterior commissure
laryngoscopy and gum bougie technique. In each circumstance bougie intubation with a
change to endotracheal intubation were accomplished smoothly and without
complication.
Transportation of an endotracheal tube over a stylet may necessitate special maneuvering.
The stylet should be lubricated with water-soluble gel and the mandible pulled forward
during insertion. This can be performed manually or more reliably with the aid of a
Macintosh blade laryngoscope, which pulls the tongue and larynx forward during blind
insertion. It can also be helpful to rotate or screw the tube over the stylet if passage
becomes difficult.
Some situations are so unique and dangerous that any elective manipulation of the airway
can produce a sequence of events in which there is no fall-back position. The
aforementioned case history might be considered in this category. It is possible to
perform cardiopulmonary bypass by means of femoral-femoral cannulation under local
anesthesia followed by intravenous anesthesia and progression through the steps of
airway control outlined herein (20). Although this process usually requires structured and
time-consuming preparation, portable bypass units can be used. Experienced surgeons
can perform femoral-femoral cannulation by means of extracorporeal membrane
oxygenation (21). This can be maintained for several days but necessitates heparinization,
which carries the risk of bleeding complications, especially with manipulation of the
airway and blood cast formation.
A fascinating technique has evolved for the management of antenatally detected head and
neck anomalies (22). Advances in ultrasonography have allowed neonatologists to
identify anomalies in utero that are incompatible with intubation of the neonate after
delivery. Epignathic tumors are organized teratomas that attach to the mandible, dorsum
of the palate, or basisphenoid portion of the nasopharynx and protrude from the mouth.
Polyhydramnios and calcifications on ultrasound are indicators of the tumor. Obstructing
lesions also are anticipated when the fetal head is held in a position of hyperextension.
Cesarean section is performed at 35 weeks. After 20 minutes of general anesthesia the
fetus is delivered up to the axilla. In the 3 to 10 minutes before maternal-fetal circulation
ceases with closure of the patent ductus arteriosus, tracheotomy can be performed. Other
obstructing conditions such as massive hemangioma of the head and neck, suspected at
color Doppler sonography, and large cystic hygroma have similarly been managed with
maternal-fetal circulation with intubation, rigid bronchoscopy, tracheotomy, cyst
aspiration, or extracorporeal membrane oxygen.
SUMMARY
The otolaryngologisthead and neck surgeon is an important participant in securing the
airway in a host of obstructive situations. Although an experienced surgeon can
confidently develop open tracheal access in most situations, a simple mechanical
alternative with high reliability must receive equal consideration. In some instances of
obstructing neck tumor or anatomic abnormalities such as severe cervical flexion,
surgical access through the neck may not be possible. Although the American Society of
Anesthesiologists has an algorithm for difficult airway, and a full textbook has been
devoted to the problem (23), the special circumstances of patients who need
otolaryngologic surgery and the unique skills and equipment peculiar to otolaryngology
provide an excellent opportunity for a sophisticated approach to airway management. A
working algorithm for the otolaryngology-anesthesiology team in the face of a lost
airway is presented in Fig 57.12 and Fig 57.13. In unanticipated airway obstruction (Fig.
57.12), the full complement of laryngoscopic equipment needed may not be immediately
available. An LMA is the most likely resource when the endolarynx cannot be visualized.
When a difficult airway is anticipated (Fig. 57.13), an anterior commissure
laryngoscopegum elastic bougie or jet ventilation stylet is preferred when the
conventional tools of the anesthesiologist do not achieve glottic visualization and
ventilation. An ETC is a clever option that has not yet been included in the lost airway
algorithm but may find its place as clinical experience progresses. Elective use of an
LMA, gum bougie and jet stylet intubation, and ETC should be subjected to trials in a
reasonable cross-section of routine surgical procedures so that a practical understanding
and confidence in their use can evolve.

FIGURE 57.12. Lost airway during anesthesia induction.
Unanticipated obstruction.



FIGURE 57.13. Lost airway during anesthesia induction.
Anticipated obstruction.




HIGHLIGHTS
Children and adults with upper airway obstruction pose several
challenges to anesthesiologists and otolaryngologisthead and
neck surgeons.
The initiation of general anesthesia and endotracheal intubation
can progress to complete life-threatening respiratory
decompensation with failure to achieve endotracheal intubation
or mask ventilation.
Hurried invasive maneuvers such as entrance to the trachea
with a large-bore needle and cricothyrotomy are recognized
salvage techniques, but other modes of extratracheal
ventilation, such as use of an LMA or ETC, are possible before
surgical airway procedures are performed.
The combined technique of anterior commissure laryngoscopy
and intubation with a gum elastic bougie or jet ventilation stylet
is preferred for achieving entrance to the trachea when
extratracheal ventilation cannot be accomplished.
An algorithm has been developed for joint management of a
problem airway by an anesthesiologist and an otolaryngologist
head and neck surgeon.
CHAPTER REFERENCES
1. Benumof JL. Management of the difficult adult airway. Anesthesiology 1991;75:10871110.
2. McCarroll SM, Lamont BJ, Buckland MR, et al. The gum-elastic bougie: old but still useful.
Anesthesiology 1988;68:643644.
3. Bedger RC, Chang JL. A jet stylet catheter for difficult airway management. Anesthesiology
1987;66:221223.
4. Spencer RF, Rathmell JP, Viscomi CM. A new method for difficult endotracheal intubation: use
of a jet stylet introducer and capnography. Anesth Analg 1995;81:10791083.
5. Brain AIJ. The laryngeal mask: a new concept in airway management. Br J Anaesth 1983;55:801
804.
6. Leach AB, Alexander CA. The laryngeal mask: an overview. Eur J Anesthesiol Suppl 1991;4:19
31.
7. Pepe PE, Zachariah BS, Chandra NC, et al. Invasive airway techniques in resuscitation. Ann Intern
Med 1993;22:393403.
8. Sofferman RA, Johnson DL, Krag DN. Laryngeal mask airway. Otolaryngol Head Neck Surg
1995;113:502507.
9. Brodrick PM, Webster NR, Nunn JF. The laryngeal mask airway: a study of 100 patients during
spontaneous breathing. Anaesthesia 1989;44:238241.
10. Sarma VJ. The use of a laryngeal mask airway in spontaneously breathing patients. Acta
Anaesthesiol Scand 1990;34:669672.
11. Wafai Y, Salem MR, Barraka A, et al. Effectiveness of the self-inflating bulb for verification of
the proper placement of the esophageal tracheal Combitube. Anesth Analg 1995;80:122126.
12. Cardiopulmonary resuscitation and emergency cardiac care: recommendations of the 1992
National Conference of the American Heart Associationcombination esophageal-tracheal tube.
JAMA 1992;268:2203.
13. Practice parameter in guidelines for management of the difficult airway. New Orleans: American
Society of Anesthesiologists, 1992.
14. Bigenzahn W, Pesan B, Frass M. Emergency ventilation using the Combitube in cases of difficult
intubation. Eur Arch Otorhinolaryngol 1991;248:129131.
15. Banyui M, Falger S, Roggla M, et al. Emergency intubation with the Combitube in a grossly obese
patient with bull neck. Resuscitation 1993;26:271276.
16. Eichinger S, Schreiber W, Heine T, et al. Airway management in a case of neck impalement: use
of the esophageal tracheal Combitube airway. Br J Anaesth 1992;68:534535.
17. Klauser R, Roggla G, Pidlich J, et al. Massive upper airway bleeding after thrombolytic therapy:
successful airway management with the Combitube. Ann Intern Med 1992;21:431433.
18. Staudinger T, Brugger S, Watschinger B, et al. Emergency intubation with the Combitube:
comparison with the endotracheal airway. Ann Intern Med 1993;322:15731575.
19. Wiltschke C, Kment G, Swoboda H, et al. Ventilation with the Combitube during tracheotomy.
Laryngoscope 1994;104:763765.
20. Rosa P, Johnson EA, Barcia PJ. The impossible airway: a plan. Chest 1996;109:16491650.
21. Duff B, Gruber B. Total tracheobronchial thrombosis due to extracorporeal membrane
oxygenation. Ann Otol Rhinol Laryngol 1996;105:259261.
22. Stocks RMS, Egerman RS, Woodson GE, et al. Airway management of neonates with antenatally
detected head and neck anomalies. Arch Otolaryngol Head Neck Surg 1997;123:641645.
23. Benumof JL. Airway management: principles and practice. St. Louis: Mosby, 1996.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

58 TRACHEOTOMY AND INTUBATION
Head & Neck SurgeryOtolaryngology
58




TRACHEOTOMY AND INTUBATION
MARK C. WEISSLER

M.C. Weissler: Department of OtolaryngologyHead and Neck Surgery, University of North Carolina
Chapel Hill, Chapel Hill, North Carolina.


Tracheotomy
History of Tracheotomy
Indications for Tracheotomy
Techniques of Tracheotomy
Complications of Tracheotomy
Complications of Percutaneous Dilational Tracheotomy
Endotracheal Intubation
History of Endotracheal Intubation
Indications for Intubation
Techniques of Intubation
Complications of Intubation
Emergency Management of the Airway
Areas for Future Study
Chapter References
Tracheotomy is the establishment of a surgical opening in the trachea for ventilation.
Tracheostomy is the opening itself, the stoma. The tube placed through the tracheal
opening is a tracheostomy tube.
TRACHEOTOMY
History of Tracheotomy
Tracheotomy, is a much older procedure than transoral or transnasal cannulation of the
trachea with a tube. The history of tracheotomy and intubation is outlined in Table 58.1
(1,2).

TABLE 58.1. HISTORY OF TRACHEOTOMY



Indications for Tracheotomy
The four basic indications for tracheotomy are to bypass upper airway obstruction, to
assist respiration over prolonged periods, to assist with the clearance of lower respiratory
tract secretions, and to prevent aspiration of oral or gastric secretions. Perhaps more
controversial are the comparative indications for tracheotomy versus intubation. Certainly
when there is mechanical or anatomic obstruction of the upper airway as by carcinoma,
translaryngeal intubation may be impossible or may carry great risk of causing further
immediate deterioration of the airway. In most cases in which there is no mechanical or
anatomic abnormality of the airway and in which the need for respiratory support is
considered of short duration, translaryngeal intubation is preferable to tracheotomy. In
cases of trauma to the larynx, attempted intubation may cause further injury or acute
deterioration of the airway.
In emergencies, the skill and knowledge of those in attendance also play a role in
deciding the best way to proceed. For example, although it may be superior to attempts at
translaryngeal intubation for a patient with laryngeal trauma and a deteriorating airway,
emergency tracheotomy is predicated on the availability of a surgeon skilled in
emergency tracheotomy in such a setting. Establishment of an airway is the most basic
tenet in the support of life; therefore, it is difficult to find fault with its attainment by
almost any means. Nonetheless, there are more or less safe and correct ways of obtaining
an airway with the least chance of causing iatrogenic harm to the patient, given an ideal
scenario and the availability of knowledgeable and skilled personnel.
Techniques of Tracheotomy
Elective Tracheotomy
Elective tracheotomy is best performed in an operating room with adequate equipment
and assistance. The patient is positioned supine with a roll between the shoulder blades to
hyperextend the neck and bring the trachea up out of the chest. A horizontal incision is
made midway between the sternal notch and the cricoid cartilage. The incision is carried
down through skin, subcutaneous tissue, and platysma muscle to reveal the strap muscles.
At the level of the strap muscles, the dissection is changed to the vertical plane. The pairs
of sternohyoid and sternothyroid muscles are separated from each other in the midline by
means of vertical incision of the fascia that connects the muscles on the two sides.
Retractors are used to pull the strap muscles to each side to reveal the thyroid isthmus.
The cricoid cartilage is identified by means of palpation through the wound, and the
overlying fascia is sectioned near its inferior border. At this level, a bloodless plane just
anterior to the trachea is identified, and the thyroid isthmus is transected and each side
suture ligated. A cricoid hook is used to pull the trachea superiorly by means of placing it
between the cricoid cartilage and the first tracheal ring. A Kittner sponge dissector is
used to push the fine fascia away from the anterior tracheal wall.

Controversy surrounds the best incision to use in the trachea. The safest incision is an
inferiorly based (Bjork) flap consisting of the second or third tracheal ring anteriorly.
This tracheal flap is sewn to the inferior skin margin and greatly reduces the risk of
accidental postoperative extubation and makes reintubation much safer should this occur.
Because of the risk of tracheocutaneous fistula with the Bjork flap, if the tracheostomy is
to be in place for only a short time, a horizontal H incision based on the second or third
tracheal ring is preferred. An alternative is to resect the anterior section of a single
tracheal ring; this procedure carries little risk of tracheal stenosis when performed on
adults (Fig. 58.1).

FIGURE 58.1. Elective tracheotomy: horizontal skin
incision, cricoid hook, and division of thyroid isthmus.



Bjork Flap
In 1960 Bjork introduced the concept of suturing an inferiorly based flap consisting of the
anterior portion of a single tracheal ring to the inferior skin margin. Use of this flap
greatly reduced the incidence of accidental decannulation and eased reinsertion of the
tracheostomy tube if accidental decannulation were to occur. The technique is
contraindicated in operations on children, among whom it can cause an unacceptable rate
of tracheal stenosis and persistent tracheocutaneous fistulae. A Bjork flap also may be
less desirable in a temporary tracheostomy, which is planned to be maintained for only
several days, such as after maxillofacial trauma or extensive surgery on the oral cavity. In
these cases, use of a Bjork flap may predispose the patient to a tracheocutaneous fistula.
This risk can be largely ameliorated if the suture securing the trachea to the skin surface
is cut at the first tracheostomy tube change. During the surgical procedure, a reinforced
tube is left in the tracheostomy, which aids in ease of positioning the patient and keeps
the bulky tracheostomy tube out of the surgeon's way. Accidental intraoperative
decannulation is prevented (Fig. 58.2).

FIGURE 58.2. Bjork flap.



When the tracheostomy is to be permanent or of long duration, the Bjork procedure can
be modified by means of defatting the surrounding skin and suturing the tracheostoma to
the skin circumferentially. This procedure is especially useful in operations on obese
patients undergoing tracheotomy because of intractable obstructive sleep apnea. A
semipermanent tracheostoma can be made that is less susceptible to maceration because it
is immediately matured by means of apposing skin to respiratory mucosa. It also allows
the tracheostomy tube to sit better and makes removal and reinsertion easier by means of
decreasing the length of the track (3). A tracheotomy wound never should be closed
tightly around the tube, and in general no suturing should be done. Suturing the wound
can lead to subcutaneous emphysema, pneumomediastinum, pneumothorax, and
infection.
Timely Tracheotomy
A timely tracheotomy is one that must be performed in 5 to 10 minutes. In such a
situation, proper lighting, some assistance, and proper equipment are usually available.
Tracheotomy in this situation is best performed through a vertical incision that extends
from the cricoid cartilage about 1.5 inches (3.75 cm) inferiorly. The incision is made
through the skin, subcutaneous tissue, platysma muscle, and pretracheal fascia. The strap
muscles are identified. The strap muscles are separated in the midline by means of rapid
sharp and blunt dissection to expose the thyroid isthmus. The cricoid cartilage is the
central landmark in any tracheotomy. A cricoid hook is inserted into the space between
the cricoid cartilage and the first tracheal ring. Superior traction on the cricoid cartilage
pulls the trachea up into the wound. The fascia on the cricoid surface near its inferior
edge is sectioned, and access is gained to a bloodless plane immediately anterior to the
trachea. Hemostats are inserted into this plane, and the thyroid isthmus is clamped and
sectioned. Blunt dissection with a sponge exposes the tracheal rings. An inferiorly based
U-shaped (Bjork) flap consisting of the second or third tracheal ring is made, and a
tracheostomy tube or endotracheal tube is inserted.
Emergency Tracheotomy
Anoxia causes death in about 4 to 5 minutes. Emergency tracheotomy, therefore, must be
performed within 2 or 3 minutes. In general, emergency tracheotomy is to be avoided. It
is too often needed because of ill-advised management of a tenuous but adequate airway.
For example, an unskilled attempt at translaryngeal intubation of a patient with bulky
glottic cancer in an improper level of anesthesia may precipitate an acute airway
emergency that can be managed with few other options. It is much better to perform
elective tracheotomy under local anesthesia than to induce such a situation. There are
good arguments for this approach in the care of a patient with laryngeal trauma and a
deteriorating airway or an infant or child who cannot undergo transoral intubation,
although this assumes a degree of sophistication, knowledge, and skill on the part of the
surgeon.
Emergency tracheotomy is best performed through a vertical incision, which begins at the
level of the cricoid cartilage and extends inferiorly about 1 to 1.5 inches (2.5 to 3.75 cm).
A right-handed surgeon uses the left hand to palpate and stabilize the larynx and to
extend the neck if there are no contraindications, such as possible cervical spine trauma,
to this maneuver. A shoulder roll also is helpful, but it usually is not germane to the
situation. The surgeon's right hand wields the blade and makes a vertical incision through
skin, platysma, and subcutaneous tissues. Structures such as the strap muscles and thyroid
isthmus rarely are identified in such a maneuver. The index finger of the left hand can be
used as a dissector to attempt to push the thyroid isthmus inferiorly and to palpate the
trachea. It is possible to avoid incising the cricoid cartilage and to position the actual
vertical tracheal incision at about the second or third tracheal ring by means of palpating
the cricoid arch with the index finger of the left hand. The vertical skin incision is crucial
to the speed of the procedure and to avoiding damage to adjacent neck structures. As long
as dissection stays in the midline in an anatomically normal neck, little irreversible
damage is done. After the incision is made in the trachea, a tracheal dilator is helpful but
not necessary to aid in the introduction of an endotracheal tube, which then is sewn to the
adjacent skin. A reinforced endotracheal tube is preferable, if available, because it resists
kinking. Bleeding in the wound is controlled after the tracheotomy is complete. If the
situation allows, the tracheotomy is carefully assessed to determine the actual location of
the tracheal incision. Revision, if necessary, is undertaken as soon as the patient's
condition allows (Fig. 58.3).

FIGURE 58.3. Emergency tracheotomy performed
through vertical skin incision.



Cricothyrotomy
In most instances, cricothyrotomy is far preferable to emergency tracheotomy. The main
advantage is that the cricothyroid membrane is near the skin surface, and much less
dissection is necessary. The procedure is easily standardized and taught to residents and
emergency department personnel. The main limitation is the risk of damage to the
subglottic larynx, but this is mostly associated with leaving the cricothyrotomy tube in
too long. Cricothyrotomy is relatively contraindicated in the care of children younger
than 12 years, patients with infection in the larynx, and patients who have sustained
laryngeal trauma and when it risks transecting a tumor.
Cricothyrotomy is performed best through a transverse incision directly over the
cricothyroid membrane. It is best for a right-handed surgeon to stand on the patient's right
side, grasp the thyroid cartilage with his or her left hand, and palpate the cricothyroid
space with the index finger of the left hand. A short stabbing incision is made with the
right hand directly through the cricothyroid membrane. Hugging the cricoid cartilage may
avoid injury to the cricothyroid artery. Once the subglottic space is entered, the handle of
the knife is inserted into the wound and twisted vertically to open the wound. An
endotracheal tube is inserted and secured (Fig. 58.4).

FIGURE 58.4. Cricothyrotomy.



Much controversy has surrounded the use of cricothyrotomy as a definitive long-term
airway. If respiratory support through a surgical airway is needed for longer than 3 to 5
days, a cricothyrotomy is converted to a tracheotomy in an elective procedure in the
operating room to avoid the long-term sequelae of subglottic stenosis, which may result
from cricothyrotomy. Esses and Jafek (2) succinctly elucidated the various arguments on
each side of this controversy.
Maneuvers to Buy Time
Several techniques have been described to ventilate a patient for a short time before more
definitive airway management can be undertaken. Transcricothyroid puncture with a 14-
gauge catheter has been described. In the care of adults, there seems to be little to
recommend this procedure over cricothyrotomy unless the physicians in attendance are
untrained in the technique. An adult cannot breathe through such a catheter, so a method
to supply oxygen under pressure, such as with an anesthesia machine or pressurized tank
or wall circuit, is necessary. A means of intermittent inflation of the lungs and control of
peak pressures also is desirable. If the oxygen is delivered under high pressure, risk of
pneumothorax is attendant. Oxygen also must have a route of egress from the lungs. If
there is obstruction at the level of the glottis, a second catheter may have to be placed
through the cricothyroid membrane to allow a route for oxygen escape; otherwise,
overinflation of the lungs with pneumothorax ensues. A variety of small pocket devices
are manufactured for use at the scene or at the roadside. I know of no controlled study of
such devices. The usefulness of these devices by untrained persons remains questionable.
Transcricothyroid puncture is perhaps more useful to children, in the treatment of whom
cricothyrotomy is best avoided if possible. Emergency tracheotomy also is best avoided.
When transoral intubation is impossible, cannulation of a child's cricothyroid membrane
with a large-bore catheter may buy enough time to allow a more orderly tracheotomy.
The same admonishments apply concerning a site of egress for delivered oxygen.
Tracheotomy in the Pediatric Patient
Vertical Incision
Performance of tracheotomy on a child is similar to the procedure on an adult. For
children, however, a simple vertical incision in the trachea is best, as shown in an animal
model (4). The incision is made in the second and third tracheal rings. Excision of any
anterior tracheal wall or the use of a Bjork flap is avoided in operations on children. If at
all possible, tracheotomy on children is performed only with a secured airway either from
intubation with an endotracheal tube or over a ventilating bronchoscope. As in the
treatment of adults, but to a greater extent, emergency tracheotomy is avoided if possible.
The smaller diameter, shorter length, and limited stability of the infantile trachea and the
greater mobility of the soft tissues of the neck and greater deformability of the tracheal
cartilage in a child call for special techniques.
Guide Sutures
During tracheotomy on a child, it is wdise to place two sutures, one on either side of the
vertical incision in the trachea, to serve as guides if the tracheostomy tube accidentally
comes out of the trachea. If such a technique is used, it is essential that the personnel
taking care of the child in the hospital be trained in the proper use of these guide sutures.
In a panic, it is easy to pull the sutures out. With gentle pulling on the sutures, the trachea
can be elevated into the wound and the incision in the trachea slightly opened to assist
reinsertion of the tube. A small 4-0 or 5-0 nonabsorbable monofilament suture usually is
used. It is removed at the first tracheostomy tube change 3 or 4 days after tracheotomy
(Fig. 58.5).

FIGURE 58.5. Pediatric tracheotomy. The vertical
incision in the trachea and guide sutures allow ease of
reintubation in the event of accidental decannulation.



Pediatric Tracheostomy Tubes
Polyvinyl chloride or polymeric silicone tubes tend to collect fewer secretions than do
metal tubes. The plastic tubes, however, have no inner cannula and are prone to
accidental decannulation owing to intrinsic malleability, which allows the tip to come out
of the trachea while the body of the tube remains in the neck wound. Pediatric
tracheostomy tubes usually have no cuff.
Percutaneous Dilational Tracheotomy
Interest in percutaneous tracheotomy has increased. This procedure began as
minitracheotomy, which was percutaneous cricothyrotomy for evacuation of bronchial
secretions in the care of critically ill postoperative patients who otherwise might simply
have remained intubated for an extended period. Most of the initial reports were by
critical care specialists and general surgeons rather than by otolaryngologists or head and
neck surgeons, for whom conventional perioperative tracheotomy has long been an
accepted method of short-term airway control. Percutaneous tracheotomy through the
first or second tracheal ring has developed into a standard technique, especially for
bedside tracheotomy of critically ill patients who need long-term ventilation in intensive
care units. It is now most appropriately called percutaneous dilational tracheotomy.
Percutaneous tracheotomy has never been safer or more effective than conventional
elective tracheotomy. The proponents of this technique emphasize as advantages a shorter
operating time, ease of performance, ability to perform the technique at the bedside, ease
with which the technique can be taught, lower expense, and lack of need to transport the
patient to the operating room with the attendant dangers associated with the transport
itself, such as dislodgment of catheters (5) (Fig. 58.6). The two procedures that most need
to be compared are bedside standard tracheotomy and bedside bronchoscopically
monitored percutaneous dilational tracheotomy. No such comparison has yet been made.
Both require sedation, special equipment, and assistance.

FIGURE 58.6. Percutaneous dilational tracheotomy with
bronchoscopic monitoring. The endotracheal tube is
pulled back into the glottis so that the puncture site can be
seen with a bronchoscope.



Complications of Tracheotomy
In the most general sense, complications can be divided into those occurring
intraoperatively, during the early postoperative period, and during the late postoperative
period (Table 58.2). During the operation, damage can be done to the great vessels or the
wall between the trachea and the esophagus. The cupula of the lung enters the low neck
and can be damaged, resulting in pneumothorax or pneumomediastinum. Although chest
radiography traditionally has been mandatory after tracheotomy, this practice after
routine noncomplicated procedures with normal results of postoperative physical
examination of the heart and lungs has been questioned (6,7).

TABLE 58.2. COMPLICATIONS
TRACHEOTOMY




Obstruction by dried mucus can be largely prevented by means of meticulous
tracheostomy care. A humidifier is used postoperatively, and the tube is suctioned
frequently after instillation of 1 to 2 mL sterile saline solution. Postobstructive pulmonary
edema is managed with mechanical ventilation with positive end-expiratory pressure and
possibly diuretics.
Cuff pressure is checked regularly and kept less than 25 cm water, the pressure at which
submucosal capillaries are occluded. For children, in the care of whom cuffed tubes
generally are not used, a slight air leak around the tube is desirable. Some patients with
severe anatomic distortion of the neck may need special tracheostomy tubes, such as a
Rusch tube. The Rusch tube is essentially a soft endotracheal tube that can be variably
advanced through the neck plate to accommodate a variety of anatomic situations.
Granulation tissue commonly forms at the level of the tracheostoma and can be present
more distally because of too vigorous tracheal suctioning.
One of the most feared complications of tracheotomy is tracheainnominate artery fistula,
which commonly occurs at the level of the tip of the tracheostomy tube and has been
ascribed to too low tracheotomy (below the level of the third tracheal ring), erosion from
a high pressure cuff, tube torsion and movement from a ventilator, and local infection.
Sixty percent of cases of fistula occur within 2 weeks of the tracheotomy, and the
complication carries a 73% mortality. Tracheainnominate artery fistula may be heralded
by a small amount of sentinel bleeding. The best initial management is to attempt to
control the hemorrhage by means of overinflating the tracheostomy tube cuff or inserting
an endotracheal tube below the level of the bleeding while attempting to compress the
innominate artery anteriorly against the sternum with a finger inserted through the
tracheotomy wound anterior to the trachea. Definitive treatment involves dividing and
suture ligating the two ends of the innominate artery (8) (Fig. 58.7).

FIGURE 58.7. Low tracheotomy resulting in trachea
innominate artery fistula.



The incidence of complications of pediatric tracheotomy is generally considered higher
than that among adults. Gianoli et al. (9) reported a 3.3% incidence of intraoperative
complications, a 13.3% incidence of early postoperative complications, and a 38.3%
incidence of late complications among children younger than 1 year. Tube obstruction
was the most common early postoperative complication, and granulation tissue was the
most common late complication (9). The mortality for the procedure itself was 1.6%, but
the overall mortality in the group of patients was 42%, reflecting the degree of underlying
illness. Duration of tracheostomy was the most important factor influencing the rate of
late complications. Higher complication rates occurred among preterm infants as opposed
to term infants, and infants undergoing tracheotomy for upper airway obstruction had
more complications than those undergoing tracheotomy for ventilator dependency. This
correlation, however, seemed to be explained by the longer survival of patients
undergoing tracheotomy for upper airway obstruction than that of those undergoing the
procedure for ventilator dependency and the subsequently greater period over which
complications had a chance to develop (8).
Complications of Percutaneous Dilational Tracheotomy
Many studies have documented the relative safety of percutaneous dilational tracheotomy
when performed by well-trained persons (10,11,12,13,14,15 and 16). Several authors
(17,18) also found an increased complication rate. The most important immedi-ate
complications include misplacement of the dilator tracheotomy tube in a paratracheal
position within the soft tissues of the neck or laryngeal structures, hemorrhage,
subcutaneous emphysema, damage to the posterior tracheal wall, and death. Long-term
complications parallel those of conventional tracheotomy, although some authors are
concerned about the possibility of a higher incidence of long-term tracheal stenosis with
this technique. Although the dilation process theoretically causes symmetric dilatation of
a hole in the anterior tracheal wall, more likely there is tearing of tracheal cartilage and
soft tissue and displacement of the wall of the trachea directly above the tracheostomy
into the tracheal lumen. Several articles imply that bronchoscopic monitoring of the
technique can add to its safety and decrease the incidence of complications (19,20 and
21). The lack of the Bjork flap increases the possibility of dislodgment of a tracheostomy
tube and makes it less likely that once the tube is displaced it can be replaced easily.
During percutaneous dilational tracheotomy on a patient who has an endotracheal tube in
place, the tube must be withdrawn to near the level of the vocal cords to afford space for
the needle and dilators. During this procedure, it is possible for the endotracheal tube to
become displaced, and unless personnel skilled at reintubation are available, acute, life-
threatening loss of airway can occur.
ENDOTRACHEAL INTUBATION
History of Endotracheal Intubation
The history of endotracheal intubation and endotracheal tubes is shown in Table 58.3.
Polyvinyl chloride tubes are probably the most commonly used tubes in the United
States. Polyvinyl chloride tubes have the unique property of softening slightly at body
temperature. Rubber tubes stiffen slightly when warmed to body temperature. Cuff
pressures greater than 25 cm water cause the submucosal capillaries to close and
eventually cause necrosis. For this reason, it is important to measure cuff pressure
periodically. Nitrous oxide can diffuse through the polyvinyl chloride of the endotracheal
tube cuff and increase cuff pressure. Special polymeric silicone, laser-safe, and reinforced
tubes are now available.

TABLE 58.3. HISTORY OF INTUBATION



Indications for Intubation
Endotracheal intubation is indicated to assist ventilation, to relieve obstruction, to
improve respiratory toilet, and to prevent aspiration. Except in the care of neonates and
possibly extensively burned patients, who usually do not undergo prolonged intubation,
endotracheal intubation is a short-term solution for 10 days to 2 weeks. If the indications
for respiratory support are expected to exceed this period, tracheotomy is performed as
soon as possible to prevent damage to the larynx and trachea caused by prolonged
intubation. Much controversy surrounds the question of prolonged intubation as opposed
to tracheotomy, but most physicians prefer tracheotomy except in the care of neonates
and patients with extensive burns, for whom the tracheostomy can be a source of
continual contamination of the burn wounds. If control of the airway is necessary because
of a planned surgical procedure on the upper aerodigestive tract, which precludes use of
endotracheal intubation, tracheotomy is preferred. The choice of intubation or
tracheotomy also depends in part on the facilities available. For example, children with
supraglottitis often are treated with short-term intubation. This approach mandates the
availability of trained personnel around the clock who can reinsert a tube that becomes
dislodged.
Techniques of Intubation
Anesthesia for Intubation
A patient undergoing intubation ideally has an empty stomach and is adequately
anesthetized and relaxed. Although this usually is the case for elective intubation in the
operating room, it rarely is the case in emergencies. In the treatment of patients who can
be adequately ventilated with a bag and mask if intubation fails, there is little danger in
giving adequate anesthesia and muscle relaxants to aid intubation. In the treatment of
patients with difficult anatomy or partial upper airway obstruction, however,
administration of such agents can cause sudden and complete loss of the airway and
necessitate emergency surgical establishment of an airway. This situation must be
avoided. When intubation is expected to be difficult, the tube is inserted while the patient
is awake. Elective awake intubation can be accomplished with standard techniques with
adequate topical and local anesthesia or over a transnasally introduced fiberoptic scope.
In some instances, such as increased intracranial pressure or certain eye trauma, the
straining and gagging that can occur with attempts at intubation on a combative or less
than fully anesthetized patient can make short-acting paralysis the procedure of choice.
Orotracheal Intubation
Orotracheal intubation is undertaken ideally with the patient in the sniffing position, the
patient's neck flexed slightly on the chest, and the head extended slightly on the neck. A
right-handed operator directs a laryngoscope into the right aspect of the mouth with the
left hand holding the scope and pushing the tongue to the left. A Macintosh laryngoscope
with a curved blade is directed into the vallecula, and the entire larynx is lifted anteriorly
or ventrally to expose the glottis. A Miller laryngoscope with a straight blade is
introduced under the epiglottis. It fixes the larynx at the petiole of the epiglottis and lifts
the larynx anteriorly to expose the glottis. Other varieties of laryngoscopes now exist, but
the Macintosh and the Miller are the most likely to be found on an emergency cart. The
right hand is used to insert the endotracheal tube, which should not be overly tight in the
glottis. In children, an air leak around the tube is desirable. Slight pressure on the cricoid
cartilage by an assistant sometimes helps to visualize the larynx. This maneuver also can
help to prevent aspiration of gastric contents by pressing the cricoid cartilage backward
against the vertebral column to close the esophagus and help prevent regurgitation. This
technique is desirable when a patient has a full stomach.
Nasotracheal Intubation
Nasotracheal intubation is used when it is important to leave the oral cavity clear of
obstruction for operative procedures, when elective intubation is performed on a patient
in whom orotracheal intubation is impossible, when endotracheal intubation is expected
to be prolonged, and in emergencies when patients are breathing spontaneously and there
is a relative contraindication to orotracheal intubation.
In elective procedures in which the patient is under general anesthesia, the nasal cavity is
topically anesthetized and decongested. It then is dilated with progressively larger nasal
airways that are copiously lubricated with viscous lidocaine or a water-soluble lubricant.
The nasotracheal tube is introduced transnasally into the pharynx, at which point a
laryngoscope is introduced through the mouth, the tube is grasped with a Magill forceps,
and the tube is introduced through the glottis.
Transnasal intubation over a fiberoptic bronchoscope can be undertaken when difficult
intubation problems are expected. In this case, the patient usually is awake, and the nose
is prepared as described earlier. Topical anesthesia to the larynx and pharynx with either
orally introduced topical agents or a superior laryngeal nerve block greatly increases
patient comfort. The surgeon stands at the patient's side or head. The otolaryngologist
may find it easier to stand at the patient's side because this is the position in which
fiberoptic laryngoscopy is undertaken in the outpatient clinic. The patient is sitting
because this prevents the larynx from falling posteriorly as it does in the supine position.
This is the position with which the otolaryngologist is familiar in the clinic. The
bronchoscope is introduced through the endotracheal tube, nose, and larynx into the
cervical trachea. The endotracheal tube is advanced over the bronchoscope and into the
trachea, and the bronchoscope is withdrawn. Most bronchoscopes used for adults cannot
be accommodated through an endotracheal tube smaller than 7F. A single bronchoscope
is used if possible because the procedure can be damaging to the bronchoscope. This
technique can sometimes also be helpful in difficult emergency situations. Mlinek et al.
(22) reported on the use of fiberoptic intubation in the emergency department. Their
success rate was 81% among the 31 patients so treated. The presence of secretions, blood,
or vomitus was the most usual cause of failure.
Blind nasotracheal intubation is indicated in the treatment of patients awake enough not
to tolerate orotracheal intubation with a laryngoscope but when there is no time to await
anesthesia or it is unavailable. Patients must be breathing spontaneously if this technique
is to be attempted. The endotracheal tube is introduced through the nose and into the
pharynx. The operator places his or her ear over the proximal end of the tube as it is
slowly advanced. When the tube is just above the glottis, the operator feels and hears the
respirations and waits for the end of an expiration to advance the tube concomitantly with
the next inspiration. Iserson (23) reported a 92% success rate using this technique on 150
patients. A variety of Ray tubes are available with an inherent bend superiorly at the level
of the lips or nares. Although these tubes can make draping easier, they also fix the
distance between the lips or nares and the tip of the endotracheal tube. These tubes can be
displaced from the glottis if the neck is extended during the operative procedure.
Intubation in Head Trauma
Head trauma raises a number of important issues for endotracheal intubation. First is the
possibility of exacerbating cervical spinal trauma with intubation. All patients with severe
head trauma are assumed to have a cervical spinal fracture until this is excluded
radiologically with radiographs of the cervical spine or other radiologic assessment.
Midfacial trauma and concern about possible fracture through the cribriform plate or
fovea ethmoidalis usually are contraindications to nasotracheal intubation for fear of
intracranial placement of the tube. Nasogastric intubation likewise is contraindicated.
Although intracranial placement of a nasogastric tube has been reported, such placement
of a nasotracheal tube has not been documented. In the treatment of patients with
suspected cervical spine fracture who need an airway secured, options include blind
nasotracheal intubation if the patient is breathing and there are no midfacial fractures,
cricothyrotomy, and orotracheal intubation with manual inline axial traction of the
cervical spine, which is the technique recommended by the American College of
Surgeons.
Patients with increased intracranial pressure or rupture of the eye can be harmed further
by the increase in intracranial pressure that accompanies difficult, struggling intubation of
a combative patient. For these patients, some authors (24) recommend use of priming
doses of pancuronium, topical lidocaine, sodium thiopental, and succinylcholine to try to
avoid increases in intracranial pressure.
Difficult Intubation with Large-bore Laryngoscope
If one performs laryngoscopy often, the situation eventually arises in which what was
expected to be a simple intubation suddenly proves difficult. One technique that can be
helpful in this situation is use of a large-bore operating laryngoscope, such as the Dedo or
Jako scope, to assist intubation. The laryngoscope usually is immediately available. The
rigid nature and wide bore of the laryngoscope allow an experienced operator to fix the
larynx and expose the glottis. An endotracheal tube with the anesthesia adapter removed
from the proximal end can be inserted through the closed tube of the laryngoscope. The
proximal end of the tube is grasped with a cup forceps to stabilize it, and the
laryngoscope is removed from around the endotracheal tube. The anesthesia adapter is
reattached, and ventilation is begun.
Use of Bronchoscope for Intubation
A rigid bronchoscope is a time-tested tool for securing an airway. An experienced
operator can secure an airway in this manner, even if attempts with other methods have
failed. Because it is rigid, the bronchoscope sometimes can be forced through a partially
obstructed glottis. The rigid bronchoscope also allows controlled suction of secretions or
blood and concomitant ventilation. Tracheotomy can be undertaken, if indicated, over a
controlled airway.
New Types of Tubes
One of several new types of airway tubes can be used, although the exact place in airway
management remains uncertain. The laryngeal mask airway and esophagotracheal
combination tube (see Chapter 57) are the most widely used. The laryngeal mask airway
has probably gained the widest acceptance for use in otherwise uncomplicated outpatient
surgery. It does not protect the airway from aspiration, but it has been used in emergency
management of the airway to buy time or when endotracheal intubation has failed. A
flexible bronchoscope can be inserted through this device, and intubation can be
performed over the bronchoscope. A laryngeal mask airway can be used as an adjunct to
flexible bronchoscopy, to assist with percutaneous tracheotomy, and during
cardiopulmonary resuscitation. The main advantages are increased speed and ease of
placement by inexperienced personnel, improved hemodynamic stability during induction
of and emergence from anesthesia, minimal increase in intraocular pressure after
insertion, reduced anesthetic requirements for airway tolerance, and lower frequency of
coughing during emergence (25). The other devices mentioned are used mostly for the
emergency control of the airway by personnel untrained in endotracheal intubation.
Several other new adjuncts to intubation include the light wand, Bullard laryngoscope,
and retrograde intubation (26).
Complications of Intubation
The complications of intubation are listed in Table 58.4.

TABLE 58.4. COMPLICATIONS INTUBATION



Acute Pulmonary Edema
Some patients who have labored under partial airway obstruction for some time can have
a rapid onset of pulmonary edema when the obstruction is suddenly relieved. This so-
called postobstructive pulmonary edema is believed to be caused by the sudden loss of
highly negative intrathoracic pressure during inspiration and positive pressure during
expiration. The result is a rapid increase in systemic venous return and subsequently in
pulmonary hydrostatic pressure with an imbalance in the pressure gradients across the
alveolar membrane. This edema can occur in the operating room or, more commonly, in
the recovery room after extubation. Frothy fluid is present in the endotracheal tube, or the
patient has hypoxia and inadequate ventilation in the recovery room. Chest radiographs
show pulmonary edema. It is managed with institution of mechanical ventilation with
continuous positive airway pressure and positive end-expiratory pressure. Diuretics also
can be helpful (27).
Improper Tube Placement
An endotracheal tube can be passed through the mucosa of the pyriform sinus into the
soft tissues of the neck. This usually occurs during difficult emergency intubations in
which excessive force has been used and can be acute with subcutaneous emphysema or
occur later with deep neck infection. The endotracheal tube can be passed into the
esophagus unwittingly. Ventilation causes gastric distention, and hypoxia occurs. Modern
carbon dioxide monitors often can detect the absence of returned carbon dioxide. The
endotracheal tube can be advanced too far, usually into the right mainstem bronchus,
which can cause atelectasis of the left lung. After intubation, the chest always is
examined by means of auscultation for equal and bilateral breath sounds. In cases of
laryngeal trauma, attempts at translaryngeal endotracheal intubation can cause further
damage to the larynx and even convert a partial injury to complete laryngotracheal
separation. For this reason, translaryngeal intubation is contraindicated in cases of
significant laryngeal trauma, unless no other means of securing the airway is available.
(Fig. 58.8).

FIGURE 58.8. Laryngotracheal separation. The tip of the
endotracheal tube is visible in the soft tissues of the right
neck (arrow). There is massive subcutaneous
emphysema.



Long-term Intubation
Laryngeal Stenosis
Long-term endotracheal intubation can damage the larynx. Largely for this reason, long-
term intubation has given way to timely tracheotomy. The injury usually occurs at the
narrowest portion of the airway. In infants and children, this is the subglottic larynx. In
adults, the glottis is the narrowest portion, and it may bear the brunt of the injury. Tube
motion, infection, and high cuff pressure add to the injury.
Tube motion can be minimized with adequate stabilization of the tube. Some authors
believe a nasotracheal tube is better stabilized by the tissues of the nasopharynx and nose
than is an orotracheal tube. Tubes of the proper size must be used. The smallest tube that
allows adequate ventilation of the patient usually is used. For children, an air leak around
the uncuffed tube is desirable. The pumping action of a ventilator adds to tube motion, as
does the thrashing of an inadequately sedated patient. Cuffs are inflated only to the
minimally occlusive volume, and cuff pressures should be monitored several times a day.
Pressures less than 25 cm water are maintained whenever possible. Neonates who have
needed long-term intubation not infrequently have subglottic stenosis, whereas adults
have ulceration of the posterior larynx, where the tube tends to sit. This can cause
intubation granuloma over the vocal processes of the arytenoids or frank glottic stenosis,
frequently posteriorly.
Tracheoesophageal Fistula
Tracheoesophageal fistula can be caused by chronic intubation. The incidence likely
increases with the concomitant presence of an endotracheal and a nasogastric tube. This
is a rare complication that often manifests as severe aspiration.
Recurrent Laryngeal Nerve Injury
The recurrent laryngeal nerve enters the larynx between the cricoid and thyroid cartilages
near their articulation and can be pinched in this position by an endotracheal tube.
Patients have recurrent laryngeal nerve paralysis.
Sinusitis
Most patients who have a nasotracheal tube in place for more than several days have
obstruction of drainage from the paranasal sinuses, which predisposes to the development
of purulent sinusitis.
EMERGENCY MANAGEMENT OF THE AIRWAY
The best technique for managing the airway in an emergency depends on the clinical
situation. In cases associated with trauma, the cervical spine must be considered unstable
until proven otherwise, and techniques aimed at protecting the spine from further
iatrogenic harm must be used. If the midface is traumatized, one must be cognizant of the
possibility of skull-base fracture, and a transnasal approach is used with great care, if at
all. The patient's level of consciousness also must be considered. Awake and alert
patients usually do not tolerate oral intubation with a laryngoscope. An algorithm for the
emergency management of the airway is shown in Fig. 58.9.

FIGURE 58.9. Algorithm for emergency management of
the airway.



AREAS FOR FUTURE STUDY
There is room for improvement in the design of endotracheal and tracheostomy tubes.
The field of biomaterials is likely to produce materials that are less traumatic to the
laryngeal and tracheal tissues. Changes in design, such as the shape of tube cuffs, are
likely to result in improved tubes in the future. New laser-safe tubes are in a state of rapid
development. New anesthetic techniques, such as the use of helium and oxygen mixtures,
may improve ventilation and decrease the risk of fire when a laser is used. This can be
especially useful in the management of partially obstructed airways.

HIGHLIGHTS
The development of tracheotomy preceded that of endotracheal
intubation by several centuries.
The four basic indications for tracheotomy and intubation are to
bypass upper airway obstruction, to assist respiration for
prolonged periods, to assist with the clearance of lower
respiratory tract secretions, and to prevent aspiration of oral or
gastric secretions.
Techniques used for tracheotomy vary with the clinical setting
and generally can be divided into emergencies, timely
procedures, and elective procedures. Emergency tracheotomy is
to be avoided whenever possible.
Cricothyrotomy is best in the emergency treatment of adults
when endotracheal intubation is contraindicated and there is no
intrinsic trauma or infection of the larynx.
Techniques such as transcricothyroid needle puncture can be
used to buy time until someone more skilled in definitive
management of the airway is available.
Pediatric tracheotomy carries risk and morbidity peculiar to it
and requires special care and knowledge.
Complications of tracheotomy can be divided into early and
late. The most common early complications are tube
obstruction and displacement. Late complications include
laryngeal and tracheal stenosis. Complications occur more
frequently among pediatric patients than among adults.
Endotracheal tubes have been developed rapidly. High-volume,
low-pressure tube cuffs are extremely useful in preventing
some of the more devastating complications of prolonged
intubation. The technique and route of endotracheal intubation
vary with the clinical situation. Orotracheal and nasotracheal
routes can be used. Blind nasotracheal intubation and intubation
over a fiberoptic bronchoscope are useful techniques in some
clinical situations.
A patient with head trauma poses special problems to the
physician concerned with securing an airway. The possibility of
cervical spinal trauma must be considered in every case.
Otolaryngologisthead and neck surgeons must be intimately
familiar with management of a critical airway. These clinicians
are uniquely qualified to deal with this difficult, life-threatening
situation.
CHAPTER REFERENCES
1. McClelland RM. Tracheostomy: its management and alternatives. Proc R Soc Med 1972;65:401
404.
2. Esses BA, Jafek BW. Cricothyroidotomy: a decade of experience in Denver. Ann Otol Rhinol
Laryngol 1987;96:519524.
3. Fee WE, Ward PH. Permanent tracheostomy: a new surgical technique. Ann Otol Rhinol Laryngol
1977;86:635638.
4. Fry TL, Fischer ND, Jones RO, et al. Comparisons of tracheostomy incisions in a pediatric model.
Ann Otol Rhinol Laryngol 1985;94:450453.
5. Leinhardt DJ, Mughal M, Bowles B, et al. Appraisal of percutaneous tracheostomy. Br J Surg
1992;79:255258.
6. Smith DK, Grillone GA, Fuleihan N. Use of postoperative chest x-ray after elective adult
tracheotomy. Otolaryngol Head Neck Surg 1999;120:848851.
7. Park SY, Smith RV. Comparison of postoperative cardiopulmonary examinations and chest
radiographs to detect pulmonary complications after adult tracheotomy. Otolaryngol Head Neck
Surg 1999;121:274276.
8. Yang YY, Criado E, Schwartz JA, et al. Trachea-innominate artery fistula: retrospective
comparison of treatment methods. South Med J 1988;81:701706.
9. Gianoli GJ, Miller RH, Guarisco JL. Tracheotomy in the first year of life. Ann Otol Rhinol
Laryngol 1990;99:896901.
10. Fischler MP, Kuhn M, Cantieni R, et al. Late outcome of percutaneous dilational tracheostomy in
intensive care patients. Intensive Care Med 1995;21:475481.
11. Caldicott LD, Oldroyd GJ, Bodenham AR. An evaluation of a new percutaneous tracheostomy kit.
Anesthesia 1995;50:4951.
12. Walz MK, Thurauf N, Eigler FW. Puncture tracheostomy in intensive care patients: technique and
results of a minimally invasive method. Zentralbl Chir 1993;118:406411.
13. Friedman Y, Mayer AD. Bedside percutaneous tracheostomy in critically ill patients. Chest
1993;104:532535.
14. Ivatury R, Siegel JH, Stahl WM, et al. Percutaneous tracheostomy after trauma and critical illness.
J Trauma 1992;32:133140.
15. Manara AR. Experience with percutaneous tracheostomy in intensive care: the technique of
choice? Br J Oral Maxillofac Surg 1994;32:155160.
16. Toursarkissian B, Zweng TN, Kearney PA, et al. Percutaneous dilational tracheostomy: report of
141 cases. Ann Thorac Surg 1994;57:862867.
17. McFarlane C, Denholm SW, Sudlow CL, et al. Laryngotracheal stenosis: a serious complication of
percutaneous tracheostomy. Anaesthesia 1994;49:3840.
18. Wang MB, Berke GS, Ward PH, et al. Early experience with percutaneous tracheotomy.
Laryngoscope 1992;102:157162.
19. Barba CA, Angood PB, Kauder DR, et al. Bronchoscopic guidance makes percutaneous
tracheostomy a safe, cost-effective, and easy-to-teach procedure. Surgery 1995;118:879883.
20. Winkler WB, Karnik R, Seelmann O, et al. Bedside percutaneous dilational tracheostomy with
endoscopic guidance: experience with 71 ICU patients. Intensive Care Med 1994;20:476479.
21. Cole IE. Elective percutaneous (Rapitrac) tracheotomy: results of a prospective trial.
Laryngoscope 1994;104:12711275.
22. Mlinek EJ, Clinton JE, Plummer D, et al. Fiberoptic intubation in the emergency department. Ann
Emerg Med 1990;19:359362.
23. Iserson KV: Blind nasotracheal intubation. Ann Emerg Med 1981;10:468471.
24. Ampel L, Hott KA, Sielaff GW, et al. An approach to airway management in the acutely head-
injured patient. J Emerg Med 1988;6:17.
25. Asai T, Morris S. The laryngeal mask airway. Can J Anesth 1994;41:930960.
26. Gonzales RM, Herlich A, Krohner R, et al. Recent advances in airway management in
anesthesiology: an update for otolaryngologists. Am J Otolaryngol 1996;17:145160.
27. Feinberg AN, Shabino CI. Acute pulmonary edema complicating tonsillectomy and
adenoidectomy. Pediatrics 1985;75:112114.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

59 CONTROVERSIES IN UPPER AIRWAY OBSTRUCTION
Head & Neck SurgeryOtolaryngology
59




CONTROVERSIES IN UPPER AIRWAY
OBSTRUCTION
AMELIA F. DRAKE
MICHAEL O. FERGUSON

A.F. Drake and M.O. Ferguson: Department of OtolaryngologyHead and Neck Surgery, University of
North CarolinaChapel Hill, Chapel Hill, North Carolina.


Evaluation of Upper Airway Obstruction
Signs and Symptoms
Diagnosis
Causes of Upper Airway Obstruction
Management of Airway Obstruction
Nonsurgical Management
Surgical Management
Controversial Topics in Upper Airway Obstruction
Effect of Nasal Obstruction on Orofacial Development
Management of Bilateral Choanal Atresia in Newborn Infants
Tracheotomy versus Cricothyroidotomy
The Technique of Tracheostomy: Open versus Percutaneous
Timing of Tracheotomy
Decannulation
Management of Subglottic Stenosis
Use of Airway Stents
Chapter References
EVALUATION OF UPPER AIRWAY OBSTRUCTION
Signs and Symptoms
Even before a history is obtained, a physical examination is essential in assessing the
severity of upper airway obstruction. The patient may use accessory respiratory muscles,
such as the sternocleidomastoid muscles, in all forms of airway obstruction. The sternal
notch and midline neck are examined for evidence of retraction. Obstruction below the
thoracic inlet does not cause suprasternal retraction, although intercostal or subxyphoid
retraction or epigastric indrawing may be present. Through observation for these features,
upper airway obstruction can be differentiated from respiratory difficulty that originates
in the lower airways.
Stridor, or noisy respiration due to obstructed airflow, is the hallmark symptom of upper
airway obstruction. Inspiratory airway noise normally is caused by obstruction at the
larynx or above. Expiratory noise can be caused by distal obstruction. Subglottic
midtracheal obstruction can manifest as biphasic stridor, that is, it is present throughout
inspiration and expiration.
In other instances of airway obstruction, the voice may be abnormal. A hoarse voice or
cry suggests laryngeal involvement. A muffled voice suggests supraglottic obstruction. A
weak cry or the lack of a glottic stop suggests vocal cord paralysis. Concomitant
symptoms such as coughing or choking suggest a specific pathologic condition, such as
unilateral vocal cord paralysis, aspiration, gastroesophageal reflux, or an anatomic defect
such as cleft of the larynx or tracheoesophageal fistula.
An accurate history is paramount. When a child has an inhaled foreign body, it is critical
to obtain the history of the choking episode. It allows the clinician to differentiate viral
croup and epiglottitis. Laryngotracheobronchitis, or croup, typically manifests with the
prodrome of antecedent upper respiratory infection and low-grade fever. It is viral in
origin and normally is caused by the parainfluenza and influenza viruses. Children 1 to 3
years of age are most commonly affected during the fall and spring. In addition to the
classic barking cough and low-grade fever, inspiratory stridor and expiratory rhonchi can
occur. Treatment relies on hydration and cool humidification, with the possible addition
of racemic epinephrine, steroids, or antibiotics, if a bacterial superinfection is suspected.
Increasing airway distress may necessitate endotracheal intubation. If so, intubation for 3
to 5 days usually is necessary. Croup usually has a slower onset than does epiglottitis, the
presentation of which is fulminant. The history includes time of onset, duration of
symptoms, severity, preexisting features, and exaggerating circumstances.
Epiglottitis is rare because of routine immunization for Haemophilus influenzae type B
infection. However, if epiglottitis is suspected, it is a medical emergency. The
symptomsdrooling, odynophagia, high fever, and stridorprogress rapidly. If the
diagnosis of epiglottitis is suspected, a team approach is initiated that relies on
otolaryngologic and anesthetic support as well as emergency department personnel.
Manipulation of the pharynx or drawing blood is deferred until the airway is stabilized in
a controlled manner. After intubation, a swab of the epiglottis and blood cultures can be
obtained while combined antibiotic therapy with ampicillin (20 to 40 mg per kilogram)
and chloramphenicol (50 to 100 mg per kilogram daily) or with one of the cephalosporins
that covers H. influenzae is initiated. Once the sensitivity of the organism is determined,
chloramphenicol can be discontinued if appropriate. Extubation can be performed within
24 hours of resolution of the fever or when a leak occurs around the endotracheal tube.
Supraglottitis also occurs among adults, but the larger adult airway can be visualized with
indirect or flexible endoscopy with less concern about laryngospasm than there is in the
care of children. Intubation may be unnecessary. Close observation, intravenous
administration of antibiotics, and hydration often are adequate.
Diagnosis
Plain radiography can be useful in certain clinical scenarios, although the sensitivity can
be low in many airway diagnoses, such as laryngomalacia (1). The lateral plain
radiographic view is preferable for delineating supraglottic airway lesions, and the
posteroanterior view is better for depiction of subglottic abnormalities. In the lateral
view, the neck is extended and the radiograph obtained during inspiration. Radiopaque
foreign bodies can be identified and located (Fig. 59.1). Fluoroscopy outlines the
relations of mobile structures such as the pharynx and shows structural and dynamic
characteristics, which can help in assessment of the probability of a retropharyngeal
abscess, for example. The site of an aspirated foreign body can be localized as the
mediastinum moves to the side of the foreign body during inspiration.

FIGURE 59.1. Radiopaque foreign body (coin) at level
of cricopharyngeus muscle.



Endoscopy is the definitive diagnostic examination of the upper airway (Table 59.1). The
examination includes nasopharyngoscopy with a flexible fiberoptic nasopharyngoscope,
which is used to assess the airway from the nasal alae to the level of the vocal cords or
subglottic larynx. Bronchoscopy also can be performed when the trachea and bronchi
must be evaluated. A flexible bronchoscope is useful for assessing the dynamic aspects of
the upper airway without the distorting mechanical forces necessary for rigid
bronchoscopy. Some anatomic structures, however, cannot be appreciated because of the
collapse of surrounding structures. Insufflated oxygen sometimes can be used to distend
these structures to allow visualization. Rigid bronchoscopy is the time-honored tool of
otolaryngologists because it allows active intervention, as in cases of aspiration of a
foreign body. Flexible nasopharyngoscopy combined with rigid bronchoscopy, or flexible
bronchoscopy alone, can be used for accurate assessment of abnormalities of the entire
upper airway.

TABLE 59.1. DIAGNOSIS



A sleep study or overnight polysomnographic recording is the standard mechanism for
evaluating a sleep disorder. It includes assessment of airflow, respiratory movement, and
periodic movements during sleep, as well as oxygen saturation monitoring and heart rate
determination. Electroencephalography, left and right electrooculography, and submental
electromyography are used to assess the presence and stage of sleep. Sleep apnea by
definition is cessation of respiratory airflow during sleep. It lasts at least 10 seconds at a
time among adults. Standard polysomnography provides several apnea measurements,
including the apnea index (number of apneic episodes per hour), hypopnea index
(number of hypopneic episodes per hour), and respiratory distress index (apnea index +
hypopnea index) (2). During inspiration, phasic contractions of the pharynx, larynx, and
tongue, especially the genioglossus muscle, help maintain normal patency of the upper
airway. During rapid eye movement sleep, however, skeletal muscle tone is inhibited,
except in the diaphragm. Any structural narrowing of the upper airway can increase
inspiratory intrapharyngeal negative pressure, which can cause partial or complete
obstruction of the pharynx.
Symptoms of obstructive sleep apnea include snoring, episodes of stopping breathing,
mouth breathing, restless sleep, daytime somnolence, and among children enuresis and
poor school performance. Tonsillar and adenoidal hypertrophy has been associated with
obstructive sleep apnea among children, and studies have shown improvement with
adenotonsillectomy. School performance also improves when sleep-associated gas
exchange abnormalities are recognized and corrected (3). Another study has shown that
adenotonsillectomy results in substantial clinical improvement even if the adenoids or
tonsils are of normal size (4).
CAUSES OF UPPER AIRWAY OBSTRUCTION
The causes of upper airway obstruction are many and varied. A practical means of
separating them is according to acute (many times over a few hours) as opposed to
chronic (over days or longer) onset. The patient's age also is important in differentiating
the cause of obstruction. Congenital airway anomalies predominate among young
children, but tumor is a much more common cause of airway obstruction among adults,
particularly a patient with the risk factors of tobacco and alcohol use. The site of
obstruction also differentiates the diagnosis. Table 59.2 lists some of the more common
causes of airway obstruction.

TABLE 59.2. CAUSES OF AIRWAY
OBSTRUCTION



MANAGEMENT OF AIRWAY OBSTRUCTION
Nonsurgical Management
The first and most important step in nonsurgical management of airway obstruction is
oxygen administration to relieve hypoxia. Patients with chronic upper airway obstruction
may need hypoxia to drive respiration; they are observed carefully for apnea, but oxygen
is not withheld. A helium-oxygen mixture of 80% helium to 20% oxygen can be used in
some cases to temporize obtaining an airway. This mixture, known as heliox, relies on the
low density of helium to transport oxygen past obstructing lesions of the larynx, trachea,
or bronchi. Use of 40% helium has been associated with the greatest increase in gas flow
through a narrowed airway, so oxygen can be added to the mixture in cases of hypoxia.
Although the cost and confusion regarding administration have limited its clinical
popularity, heliox therapy can improve ventilation temporarily until definitive control of
the airway can be obtained. In transient instances of airway obstruction, heliox treatment
can eliminate the need for intubation or tracheotomy. The most important limitation is the
need for additional oxygen in cases of severe hypoxia (5).
Epinephrine aerosols can be useful in acute airway obstruction with an element of soft-
tissue edema, such as croup. They act as topical decongestants. In hypoxia, the nebulizer
is driven with oxygen. Racemic epinephrine given with intermittent positive-pressure
breathing has been most effective in relieving upper airway obstruction; however, the
effect is of short duration, and there can be a rebound effect once the initial effect
subsides. For this reason, inpatient observation is advocated for any patient who receives
nebulized racemic epinephrine in the emergency department.
The use and dosing of steroids, with or without topical vasoconstrictors, in the
management of airway obstruction have been controversial in the past. The last few years
have witnessed an increase in the clinical use of systemic and topical glucocorticoids.
Studies of animals showed that large doses of dexamethasone sodium phosphate (about 1
mg per kilogram) were effective in a ferret model of postintubation croup (6). Large
doses of dexamethasone have been helpful in the hospital treatment of patients with
severe croup.
Adjuncts in airway support (oropharyngeal and nasopharyngeal airways) have a distinct
place in the care of patients emerging from anesthesia or with an altered mental status
from another cause. The oropharyngeal airway prevents ventilatory obstruction due to
relaxation of tongue. It also helps avoid obstruction from biting an endotracheal tube
already in place. If incorrectly placed, an oropharyngeal airway can cause airway
obstruction by pushing the tongue posteriorly into the hypopharynx. If the device is
positioned when the patient is in a light plane of anesthesia, coughing and laryngospasm
can occur. The nasopharyngeal airway is an alternative means of adjunctive airway
support. Nasal or nasopharyngeal trauma can cause bleeding during insertion.
Transtracheal positive-pressure ventilation can be given through a large-bore (16-gauge)
angiocatheter to manage upper airway obstruction. It offers rapid access to the airway in
acute life-threatening upper airway obstruction and provides control of the airway when
the anatomic features, as a result of trauma or tumor, make conventional airway
management difficult. Complications include subcutaneous emphysema, pneumothorax,
and catheter displacement. Successful, safe use of the technique necessitates
understanding the limitations and risks. Percutaneous transtracheal jet ventilation is
considered in acute upper airway obstruction but is not a substitute for intubation or
tracheotomy (7).
For adults with chronic upper airway obstruction, medical management is the initial
treatment route and includes diet modification, avoidance of alcohol and sedatives, and
alteration of sleep habits. Because these behavioral modifications are not typically
successful, mechanical devices designed to improve oropharyngeal mechanics are the
next step in the treatment algorithm. Most adults with obstructive sleep apnea (OSA)
need nasal continuous positive airway pressure (CPAP). If used consistently and
correctly, this nonsurgical treatment is effective in the management of OSA and has been
shown to reduce mortality among patients with OSA. Nasal CPAP, however, often is
poorly tolerated. The result is decreased patient compliance and decreased overall
effectiveness of nasal CPAP. For these patients, surgical treatment is the only remaining
option (8,9).
Surgical Management
Surgical management of upper airway obstruction depends on the suspected cause, the
degree of obstruction, and the clinical presentation (Table 59.3). After direct trauma to
the neck with progressive breathing difficulty, intubation is contraindicated because of
the possibility of laryngotracheal separation. More often, however, these patients have
minimal symptoms despite serious injury. Hoarseness, pain, or dyspnea may be present,
as may dysphagia if the cervical esophagus has been traumatized. Neck palpation can
show crepitus, edema, or instability of the external laryngeal framework. The possibility
of a concomitant cervical spinal injury always is kept in mind. In such cases, expeditious
laryngoscopy can be used to assess the integrity of the larynx and proximal trachea.
Temporary tracheotomy is the safest access procedure if a separation is suspected.
Immediate surgical correction of the laryngeal or tracheal abnormality is undertaken
because permanent scarring and stenosis are the sequelae of delayed diagnosis and
treatment. Table 59.4 lists indications for surgical exploration of the larynx in the
treatment of patients with suspected laryngotracheal trauma.

TABLE 59.3. TREATMENT



TABLE 59.4. INDICATIONS FOR SURGICAL
EXPLORATION IN LARYNGOTRACHEAL
TRAUMA



The most common cause of chronic upper airway obstruction among children is
adenotonsillar hypertrophy. The most common surgical treatment is adenotonsillectomy.
The symptoms of chronic upper airway obstruction among children include mouth
breathing, snoring, nocturnal apnea, daytime somnolence, and enuresis. Behavioral
sequelae include daytime sleepiness and poor school performance (3). In more severe
cases, cor pulmonale or systemic hypertension occurs.
Much misinformation exists among the general public about adenotonsillectomy, largely
because of the frequency with which it was performed in the 1960s and 1970s.
Indications are clearer and more specific today, They address two components of the
Waldeyer throat ring, the adenoids and the tonsils, independently. One common
misconception is that removing this lymphatic barrier heightens the incidence of
infectious illness. Unlike splenectomy, however, which results in an increased incidence
of pneumococcal sepsis, adenotonsillectomy does not increase the likelihood of
overwhelming infection. Results of studies indicating a possible increase in Hodgkin
disease among these patients have not been substantiated.
Adenotonsillectomy continues to be associated with the unlikely but serious complication
of severe hemorrhage. Electrocauterization has decreased the frequency of immediate
hemorrhage, but delayed bleeding continues to have a high morbidity and may cause
death. Velopharyngeal inadequacy can occur after adenoidectomy. If there is no
submucous cleft of the palate, this complication usually is short-lived and resolves
spontaneously in a few weeks. The rare complication of nasopharyngeal stenosis can be
corrected surgically with laterally based pharyngeal rotation flaps (10).
Among adults, chronic upper airway obstruction manifests as snoring or noisy
respiration, nocturnal apnea, and daytime somnolence. There are many surgical options,
although none has shown evidence of consistent long-term success. The first surgical
treatment commonly made available to the public is uvulopalatopharyngoplasty (UPPP),
introduced by Fujita in 1981 (11). Although its use is widespread, UPPP is effective for
fewer than 50% of patients with OSA. It is, however, highly effective in the management
of snoring. Most investigators report success rates greater than 90%. The limitation of
UPPP is its high morbidity. It necessitates general anesthesia and causes substantial
postoperative pain. Postoperative complications include airway obstruction, hemorrhage,
and velopharyngeal insufficiency (11).
To combat the high morbidity, newer procedures have been developed for snoring to
attempt to equal the effectiveness of UPPP while eliminating the more bothersome side
effects. Laser-assisted uvuloplasty (LAUP), introduced in 1993, is an office-based
procedure that has advantages of no general anesthesia, increased safety, and decreased
time in the hospital. However, LAUP can be equally as painful as UPPP, the cost is
equivalent to that of UPPP, and in most cases, several procedures are needed for success
(12).
The most recent advance in the management of upper airway obstruction is the use of
radiofrequency tissue volume reduction, known commonly as somnoplasty.
Radiofrequency ablates submucosal tissue through liquefaction necrosis. The result is
scarring and contraction of the soft tissue and resolution of upper airway obstruction. It is
most commonly used on the soft palate to control snoring, although use on the tongue
base to manage of OSA is being investigated. Somnoplasty is advantageous because it is
a relatively painless outpatient procedure with short-term results equal to those of both
the UPPP and LAUP procedures (13). The disadvantages include the cost, the need for
several procedures, and the lack of long-term data regarding effectiveness.
Other surgical procedures are specifically designed to correct the anatomic cause. For
mandibular retrognathism with class II malocclusion associated with obstructive sleep
apnea, mandibular advancement by means of sagittal split osteotomy can correct the
abnormality. Geniotubercle advancement and hyoid suspension also have been used to
increase pharyngeal airway space. If a large tongue is the cause, base-of-tongue resection
has been performed, although concomitant tracheotomy is performed. Newer techniques,
such as distraction osteogenesis of the mandible, have met with preliminary success in
the form of early decannulation or avoidance of tracheostomy by some patients with
severe mandibular hypoplasia.
CONTROVERSIAL TOPICS IN UPPER AIRWAY OBSTRUCTION
Effect of Nasal Obstruction on Orofacial Development
A hotly debated topic is the effect of nasal obstruction on orofacial development. The
only consensus appears to be that continuing longitudinal research is needed to establish
causality. In the middle of the nineteenth century, a relation was described between
enlarged tonsils, mouth breathing, and certain dental anomalies such as a narrow
maxillary arch. The adenoid face, or long-faced, syndrome was thought to represent the
facial features of low tongue posture and the unbalanced compressive forces of buccal
musculature on the posterior maxillary teeth. The opposing camp argues that many of
these orofacial anomalies are genetic in origin.
In the most widely cited animal study, performed by Harvold et al. (14), total nasal
obstruction was produced in rhesus monkeys by means of placing plastic plugs in the
nose. Oral respiration developed. The malocclusion and skeletal changes were not
uniform among the animals. These adaptive changes could not be reversed in all the
animals when the obstructing plugs were removed. The suggestion was that some
patterns may not be reversible when the obstruction is relieved.
Research is needed to answer the question of cause and effect. Much of the literature
includes evaluation of nasal obstruction through visual observation of mouth breathing,
radiologic examination, or rhinometry. Another respirometric technique for assessing
airway impairment is estimating the smallest cross-sectional area in an airway.
Modification of the theoretic hydraulic principle allows assessment of airway size (15).
Other techniques entail respiratory induction plethysmography. Although predominantly
used as research tools, these techniques have added to our understanding of what
constitutes nasal airway impairment.
Management of Bilateral Choanal Atresia in Newborn Infants
One case of choanal atresia occurs in every 5,000 to 8,000 livebirths with a 2:1 female-
to-male preponderance. Other congenital anomalies often are present. Cyclic cyanosis is
a hallmark of the clinical presentation. The infant is an obligate nose breather because the
posterior soft palate covers the oropharynx. When the mouth is closed, the infant cannot
inspire and becomes cyanotic. When the infant cries, airflow occurs through the mouth,
and the cyanosis is relieved. With increasing facial growth, mouth breathing is possible,
usually by 8 to 12 weeks of age. The diagnosis of choanal atresia is made when a catheter
cannot be passed more than 32 mm past the anterior nares.
There is immediate concern for the airway of a newborn with total nasal obstruction such
as that resulting from bilateral choanal atresia. The obstruction can be managed with
orotracheal intubation or an oral airway that opens the mouth. An endotracheal tube
placed transorally into the esophagus opens the mouth and can be used for feeding. A
McGovern nipple (a large nipple with the end cut off) makes it possible for an infant to
mouth breathe between swallows while feeding. Ties or tape can secure the nipple to the
infant as an oropharyngeal airway.
Computed tomography helps in preoperative planning by delineating the anatomic
relations (Fig. 59.2). The atretic plate can be membranous or bony. Surgical repair can be
transnasal or transpalatal. The transnasal route is simpler. Repair by this route is easier to
perform and can be done on very young infants but is more likely to result in restenosis.
Endoscopic telescopes have simplified the transnasal approach. Therefore, this approach
usually is recommended initially. The transpalatal route allows better visualization and is
associated with a decreased incidence of restenosis. An infant with CHARGE association
(coloboma, heart defects, atresia of the choanae, retardation, genital hypoplasia, and ear
anomalies) offers additional management challenges.

FIGURE 59.2. Computed tomographic scan shows
bilateral choanal atresia and medial displacement of the
lateral walls of the nasopharynx.



Tracheotomy versus Cricothyroidotomy
Cricothyroidotomy is the surgical procedure of making an incision through the skin and
cricothyroid membrane (Fig. 59.3). This simple, quick procedure has been advocated as
preferable to tracheotomy in the treatment of patients who need emergency surgical
airway intervention. The roles of cricothyroidotomy and traditional tracheotomy have
been debated before and since Jackson's landmark 1921 paper, in which he condemned
high tracheotomy as the most common cause of chronic laryngeal and subglottic stenosis
(16). The diseases that cause acute laryngeal edema included tuberculosis and syphilis
and are uncommon today. Proponents and opponents of the procedure would agree with
Jackson's original contention that cricothyroidotomy is not to be performed on patients
with acute laryngeal disease. Most also would agree that in cases of urgent airway
compromise, the faster, simpler procedure is used. There are fewer acute complications
such as bleeding or pneumothorax with cricothyroidotomy than with tracheotomy. The
procedure can be taught to those with little surgical training, such as military corpsmen,
and can be performed with few instruments, such as a pocketknife and a straw or barrel
of a pen for a tube. More than half of the complications in emergency tracheotomy
reportedly are caused by a delay in performing the procedure. Thus cricothyroidotomy
compares favorably with tracheotomy in situations demanding emergency airway access.

FIGURE 59.3. Cricothyroidotomy versus traditional
tracheotomy.



The greater debate lies in evaluating elective cricothyroidotomy as a safe alternative to
tracheotomy. This issue has been examined in particular for patients undergoing median
sternotomy in whom a tracheotomy site might contaminate a larger chest-wall wound.
The most impressive series was that of Brantigan and Grow (17). On 655 patients who
needed sternotomy these investigators performed elective cricothyroidotomy for
anticipated lengths of mechanical ventilation greater than 48 hours. The reported
complication rate was 6.1%, although personal follow-up evaluation was not conducted
with all the patients. No patient had chronic subglottic stenosis. The chief disadvantage in
this series, as in others, appears to be the development of voice changes after
decannulation15% in one study (18) compared with 8% after oral intubation alone.
One of the several theoretic causes of voice problems after cricothyroidotomy is that
distending the cricothyroid muscles reduces tension on the vocal cords. The result is a
clinical scenario similar to that of paralysis of the superior laryngeal nerve.
Immobilization and arthritis of the cricothyroid joint have also been theorized to occur
(18).
The recommendation is that any anticipated long-term cricothyroidotomy be converted to
a tracheotomy as soon as possible. This was not done in the series described by Brantigan
and Grow (17), but there was no reported adverse effect. It is uncertain whether this step
diminishes the risk of subglottic stenosis, but it certainly removes an ongoing nidus for
the development of granulation, chondritis, and scar formation.
Otolaryngologists, unlike general surgeons, continue to oppose the elective use of
cricothyroidotomy, primarily because of concern about development of subglottic
stenosis. Otolaryngologists deal more intimately with trying to correct subglottic stenosis
and favor any preventive action to avoid this complication. This complication also can be
caused by intubation that may exist before the procedure (Table 59.5). The literature is
controversial. Reported complication rates differ for both procedures. Tracheotomy is
routinely, rapidly performed by otolaryngologists before many other head and neck
procedures, but trauma surgeons may favor cricothyroidotomy for speed and control.
This procedure also is more appropriate in emergencies. Few topics in airway obstruction
are more controversial than the choice between tracheotomy and cricothyroidotomy. For
this reason, and because each procedure has distinct advantages and disadvantages, both
techniques probably will continue to exist for a long time.

TABLE 59.5. COMPLICATIONS INTUBATION



The Technique of Tracheostomy: Open versus Percutaneous
Since the mid 1980s, surgeons have performed bedside percutaneous tracheotomy,
advocating this procedure as more efficient and cost effective than traditional surgical
tracheotomy (19,20). The percutaneous method consists of passing a needle into the
trachea, placing a J-tipped guidewire, progressively dilating the tracheostomy, and
placing the tracheotomy tube (21). Reduced cost, decreased operative time, less bleeding,
smaller scar, ease of learning, fewer personnel, reduced infection, and less tracheal
erosion are all proposed benefits of this technique (19). Adverse events associated with
the percutaneous method include pneumothorax, hemorrhage, aborted procedure,
laryngotracheal injury, and death (22,23). In a study of the issue of transportation of the
intensive care unit patients to the operating room, the investigators found no increase in
risk of complications during tracheotomy during transportation (24). At this time,
conventional surgical tracheotomy performed in a controlled setting by experienced
personnel remains the standard by which newer procedures are evaluated. Table 59.6
describes other emergencies in the upper airway and possible complications.

TABLE 59.6. EMERGENCIES



Timing of Tracheotomy
The optimal timing of tracheotomy is debatable. The procedure is delayed long enough to
allow extubation if possible, but it is performed early enough to avoid complications
related to long-term intubation, such as intubation granuloma, posterior commissure
stenosis, edema, and subglottic stenosis (Fig. 59.4; see also Color Plate 17 following p.
370). The low-pressure cuffs on endotracheal tubes can cause localized tracheomalacia,
which differs from the firm cicatrix that occurs when a high-pressure balloon causes
localized ischemia, mucosal injury, and chondritis (Fig. 59.5).

FIGURE 59.4. Acquired subglottic stenosis due to
intubation. (See also Color Plate 17 following p. 370.)



FIGURE 59.5. Localized tracheomalacia (left) and rigid
cicatrix (right), both complications of cuff trauma.



Endotracheal intubation is associated with an increased incidence of laryngeal injury,
most notably posterior commissure stenosis, but tracheotomy can cause more immediate
and severe complications, including bleeding and pneumothorax (0% to 5% incidence
among adults and as high as 20% reported incidence among children). The benefits of
tracheotomy include increased efficiency of suctioning, increased mobility and comfort
for the patient, decreased incidence of accidental extubation, and avoidance of laryngeal
injury. Risks, in addition to the immediate surgical ones, include bacterial contamination,
increased risk of lower airway infection, and the possibility of tracheal injury and
stenosis.
The risk of damage from an endotracheal tube appears to be related to the length of
intubation (Table 59.5). It is theorized that injury occurs from movement of the tube and
pressure necrosis. A prospective study of intubated patients revealed a 6% incidence of
transient injury among patients with a tube in place 2 to 5 days, a 5% incidence of
irreversible injury among patients with a tube 6 to 10 days, and a 12% incidence of
extensive translaryngeal injury among patients with a tube 11 to 24 days (25). Therefore
evaluation is warranted 7 to 10 days after intubation to check for the likelihood of
extubation. If long-term intubation is probable, tracheotomy is justified. For some
patients, notably those with neuromuscular disorders such as Guillain-Barr syndrome,
for whom long-term ventilatory support can be predicted, early tracheotomy is more
humane.
No ideal prospective, randomized study has been performed to compare prolonged
translaryngeal intubation with tracheotomy in the care of patients undergoing mechanical
ventilation. Therefore the patient's need for airway support is individualized, and the
potential risks and benefits are weighed when this decision is made.
Decannulation
Decannulation protocols vary widely. The most important consideration is safe, accurate
assessment of airway patency before decannulation is initiated. Among adults with
tracheostomies, the proximal airway usually can be visualized with a flexible
laryngoscope inserted through the nose to examine the larynx and retrograde through the
tracheostoma to evaluate the upper trachea. If there is vocal cord impairment, evidence of
residual edema, or suprastomal granulation, decannulation is postponed until the
pathologic condition is controlled or resolves spontaneously. When the airway is
adequate, the tracheostomy tube can be made smaller and plugged. If this is tolerated, the
tracheostomy tube can be removed and the tracheostoma covered with an occlusive
dressing.
Tracheostomy decannulation of children is more controversial. Decreasing the size of the
tube and plugging it are advocated for older children. Bronchoscopy often is performed
before decannulation is attempted because tracheal granulation can be prominent. For
infants and young children, the tracheostomy tube itself can cause enough obstruction to
interfere with adequate respiration. Mucous plugging and additional turbulence can
exacerbate the problem. In the care of these patients, decannulation and close observation
can be accomplished during the same hospitalization as the bronchoscopy if the
evaluation confirms a good airway. After removal of the cannula, the child is observed in
the hospital with an occlusive dressing over the tracheostoma. In most instances, the child
can be discharged 48 hours after decannulation and undergo follow-up evaluation as an
outpatient. If the stoma does not close spontaneously, follow-up bronchoscopy 3 to 6
months later is recommended to ensure an adequate airway. At that time, the skin-lined
track can be excised and closed in three layers with a rubber band drain.
Management of Subglottic Stenosis
Subglottic stenosis is congenital or acquired, usually through endotracheal intubation but
occasionally by means of external trauma, tumor, thermal injury, or high tracheotomy.
Congenital subglottic stenosis is soft tissue or cartilaginous in nature. Cartilaginous
subglottic stenosis can be defined at histopathologic examination as an abnormally
shaped cricoid, a congenitally small cricoid of normal shape, or a trapped first tracheal
ringan unusual condition in which the first tracheal ring is found embryologically
inside the cricoid (26). Sometimes the true cause of subglottic stenosis is difficult to
determine. A congenitally small cricoid cartilage can be more at risk of acquired stenosis.
Traditional management of acquired subglottic stenosis among children in whom a lumen
remains has been serial dilation (also known as bougienage) while awaiting growth.
Resecting the area of stenosis can be difficult because of its proximity to and frequent
involvement with the larynx. Concern over the small size of the larynx and possible
interference in its subsequent growth had precluded other aggressive surgical procedures.
However, sine the early 1980s, open repair of the stenotic area has been performed by
means of anterior cricoid split and laryngotracheal reconstruction. These procedures
compare favorably with the traditional methods in terms of number of patients who can
undergo decannulation, time to decannulation, and voicemore patients treated with
dilation were aphonic (27). Open reconstructive procedures, such as costal cartilage
grafting and cricotracheal resection, add another dimension to the care the
otolaryngologist can offer a patient with subglottic stenosis (28).
Use of Airway Stents
The use of stents in the airway is one of the most controversial topics in airway
obstruction. The main purpose of airway stenting is to counteract scar contracture and to
provide support for healing, either from acute traumatic injuries or from reconstruction of
laryngeal or tracheal stenosis. Even whether to use a stent is controversial. Some authors
argue that stents cause additional trauma to an already traumatized airway.
Types of stents include endotracheal tubes, polymeric silicone sheet rolls, Montgomery T
tubes, and laryngeal stents. Montgomery T tubes and laryngeal stents have been used
widely with good results. Polymeric silicone sheeting in a roll, as reported by Ochi et al.
in 1992 (29), has a tendency to unroll, putting constant pressure on the mucosa. Aboulker
introduced a hollow cylindrical stent of polished polytetrafluoroethylene (PTFE), which
is fairly inert and offers excellent support (30). Less granulation tissue is produced with
this stent than with the Montgomery T tube or polymeric silicone Montgomery stent.
Indications for the use of a stent in the airway are moderate or severe stenosis in the
supraglottic, glottic, or subglottic larynx or trachea, including situations in which a
cartilage graft is used. The duration of the stent depends on the anatomic features, such as
total stenosis with complete obstruction, the consistency of the stenosis, the stability of
the graft, and the tendency to scar, evidenced by keloids elsewhere. The duration of
stenting also varies depending on the surgeon, patient, stent used, and surgical
reconstruction. Different authors recommend different lengths of time for stenting that
range from 1 to 13 months (30).

HIGHLIGHTS
Transtracheal positive-pressure ventilation can be life saving in
the management of acute upper airway obstruction.
Tracheotomy is the safest access procedure if laryngotracheal
separation is suspected.
Cricothyroidotomy is an excellent choice for emergency
surgical airway access, but it is contraindicated if the patient
has acute laryngeal disease.
The risk of damage from an endotracheal tube is related to the
length of intubation.
The anterior cricoid split procedure is considered before
tracheostomy in the care of infants with adequate pulmonary
reserve when extubation fails because of edema.
Bronchoscopy is considered before tracheostomy decannulation
in the care of children to rule out obstructing tracheal
granulation.
Severe subglottic stenosis in children is more efficaciously
managed with open surgical techniques than with serial
dilation.
Indications for the use of a stent in the airway are moderate or
severe stenosis in the supraglottic, glottic, or subglottic larynx
or trachea, including situations in which a cartilage graft is
used.
Tonsillectomy and adenoidectomy can improve school
performance among children with sleep-disordered breathing.
CHAPTER REFERENCES
1. Walner DL, Donnelly LF, Ouanounou S, et al. Utility of radiographs in the evaluation of pediatric
upper airway obstruction. Ann Otol Rhinol Laryngol 1999;108:378383.
2. Rundell OH, Jones RH. Polysomnography methods and interpretation. Otol Clin North Am
1990;23:583.
3. Gozel D. Sleep-disordered breathing and school performance in children. Pediatrics
1998;102:616620.
4. Butt W, Robertson CF, Phelan PD. Snoring in childhood: is it pathological? Med J Aust
1985;143:335.
5. Orr JB. Helium:oxygen gas mixtures in the management of patients with airway obstruction. Ear
Nose Throat J 1988;67:867.
6. Woods CI, Postma DS, Prazma J, et al. Effects of dexamethasone and oxymetazoline on
postintubation croup: a ferret model. Otolaryngol Head Neck Surg 1987;96:554.
7. Weymuller EA Jr, Pavlin EG, Paugh D, et al. Management of difficult airway problems with
percutaneous transtracheal ventilation. Ann Otol Rhinol Laryngol 1987;96:34.
8. He J, Kryger MH, Zorick FG, et al. Mortality and apnea index in obstructive sleep apnea. Chest
1988;94:914.
9. Anand VK, Ferguson PW, Schoen LS. Obstructive sleep apnea: a comparison of continuous
positive airway pressure and surgical treatment. Otolaryngol Head Neck Surg 1991;105:382390.
10. Cotton RT. Nasopharyngeal stenosis. Arch Otolaryngol 1985;111:146.
11. Fujita S, Conway W, Zorick F, et al. Surgical correction of anatomic abnormalities in obstructive
sleep apnea syndrome: uvulopalatopharyngoplasty. Otolaryngol Head Neck Surg 1981;89:923
934.
12. Kamami YV. Outpatient treatment of sleep apnea syndrome with CO
2
laser: laser assisted UPPP. J
Otolaryngol 1992;23:395398.
13. Coleman SC, Smith TL. Midline radiofrequency tissue reduction of the palate for bothersome
snoring and sleep disordered breathing: a clinical trial. Otolaryngol Head Neck Surg
2000;122:387394.
14. Harvold EP, Chierici G, Vargervik K. Experiments on the development of dental malocclusions.
Am J Orthod Dentofacial Orthop 1972;61:38.
15. Warren DW. Effect of airway obstruction upon facial growth. Otol Clin North Am 1990;23:699.
16. Jackson C. High tracheotomy and other errors the chief cause of chronic laryngeal stenosis. Surg
Gynecol Obstet 1921;32:392.
17. Brantigan CO, Grow JB. Cricothyroidotomy revisited again. Ear Nose Throat J 1980;59:289.
18. Mitchell SA. Cricothyroidotomy revisited. Ear Nose Throat J 1979;58:54.
19. Toye FJ, Weinstein JD. Clinical experience with percutaneous tracheostomy and
circothyroidotomy in 100 patients. J Trauma 1986;26:10341040.
20. Griggs WM, Myburgh JA, Worthley LIG. A prospective comparison of a percutaneous
tracheostomy technique with standard surgical tracheostomy. Intensive Care Med 1991;17:261
263.
21. Ciaglia P, Graniero KD. Percutaneous dilational tracheostomy results and long term follow-up.
Chest 1992;101:464467.
22. Wang MB, Berke GS, Ward PH, et al. Early experience with percutaneous tracheotomy.
Laryngoscope 1992;102:157161.
23. McFarlane C, Denholm SW, Sudlow CLM, et al. Laryngotracheal stenosis: a serious complication
of percutaneous tracheostomy. Anaesthesia 1994;49:3840.
24. Henrich DE, Blythe WR, Weissler MC, et al. Tracheotomy and the intensive care unit patient.
Laryngoscope 1997;107:844847.
25. Whited RE. A prospective study of laryngotracheal sequelae in long-term intubation.
Laryngoscope 1984;94:367.
26. Tucker GF, Ossoff RH, Newman AN, et al. Histopathology of congenital subglottic stenosis.
Laryngoscope 1979;89:866.
27. Pashley NRT. Serial dilation compared to elective laryngotracheoplasty in the treatment of
acquired subglottic stenosis in children. Int J Pediatr Otorhinolaryngol 1983;5:59.
28. Monnier P, Lang F, Savary M. Cricotracheal resection for pediatric subglottic stenosis. Int J
Pediatr Otorhinolaryngol 1999;49[Suppl 1]:S283S286.
29. Ochi JW, Evans JN, Bailey CM. Pediatric airway reconstruction at Great Ormond Street: a ten-
year review, I: laryngotracheoplasty and laryngotracheal reconstruction. Ann Otol Rhinol Laryngol
1992;101:465468.
30. Zalzal GH. Use of stents in laryngotracheal reconstruction in children: indications, technical
considerations, and complications. Laryngoscope 1988;98:849.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

60 INFECTIONS OF THE DEEP SPACES OF THE NECK
Head & Neck SurgeryOtolaryngology
60




INFECTIONS OF THE DEEP SPACES OF THE
NECK
BRUCE A. SCOTT
CHARLES M. STIERNBERG
BRIAN P. DRISCOLL

B.A. Scott: Department of Surgery, Division of Otolaryngology, University of Louisville School of
Medicine, Louisville, Kentucky.
C.M. Stiernberg: University of Texas Health Science Center at Houston, Houston, Texas.
B.P. Driscoll: Department of Otolaryngology, University of Texas Medical Branch at Galveston,
Galveston, Texas.


Etiology
Anatomy of the Cervical Fascia
Anatomy of Deep Neck Spaces
Spaces Involving Entire Length of Neck
Spaces Limited to Above the Hyoid Bone
Space Limited to Below the Hyoid Bone: Anterior Visceral Space
Bacteriology
Diagnosis
Management
Complications
Emergencies
Specific Deep Neck Infections
Retropharyngeal Space Infections
Danger Space Infections
Prevertebral Space Infections
Visceral Vascular Space Infections
Pharyngomaxillary Space Infection
Submandibular Space Infection
Masticator Space Infections
Peritonsillar Space Infections
Temporal Space Infection
Anterior Visceral Space Infection
Chapter References
The advent of antibiotics decreased the incidence and mortality of infection of the deep
spaces of the neck (1). Antibiotics also have altered the causation and management of this
disease. Although still considered surgical diseases, some early infections respond to
antibiotics alone. Despite these gains, infections of the deep spaces of the neck remain
life threatening. A delay in diagnosis or inadequate or inappropriate treatment can lead to
dire complications, such as mediastinitis, which has a mortality rate as high as 40% (2).
Head and neck surgeons must have a precise knowledge of the cervical fasciae and the
potential spaces they define to understand the management and complications of this
disease.
ETIOLOGY
In the era before antibiotics, 70% of deep neck infections were caused by spread from
pharyngeal and tonsillar infections. As a consequence, the parapharyngeal space was
most commonly involved (1). An increasing percentage of infections are caused by dental
and salivary gland infections, which often involve the submaxillary space. Odontogenic
sources are the most common origin of deep neck infections among adults (3,4). Other
causes include salivary gland infection, upper respiratory tract infection, trauma, presence
of a foreign body, instrumentation, and spread of localized or superficial infection.
Among as many as 20% of patients, the origin remains unknown (5). Previously
undiagnosed congenital deformities, such as branchial cleft sinus, explain a portion of
these cases (6). In the pediatric population, tonsillar and upper respiratory infections are
the most common causes of deep neck infection.
In addition to the classic origins of infection, the head and neck surgeon may see
infection of the deep spaces of the neck among persons who abuse intravenous drugs.
There is evidence that intravenous drug abuse is the most common cause of deep neck
infections in inner city areas (4,5). Drug addicts, who frequently use contaminated
needles, often inject drugs into the major vessels of the neck, violating the protective
cervical fascia, contaminating the deep neck spaces, and placing themselves at risk of
severe infection. The vascular space, which contains the carotid artery, is especially
prone to infection, and the diluents that often are found in illegal drugs, such as talcum
powder, lactate, and quinine, may contribute to the patient's morbidity (6).
ANATOMY OF THE CERVICAL FASCIA
The presentation, spread, and management of infection of the deep spaces of the neck are
based on the anatomic configuration of the cervical fascia (3,7,8). The cervical fascia is
composed of fibrous connective tissue layers that enclose organs, muscles, nerves, and
vessels and separate the neck into a series of planes and potential spaces (Fig. 60.1, Fig.
60.2). The fascia is divided into a superficial cervical fascia and a deep cervical fascia;
the latter is subdivided into superficial, middle, and deep layers (Table 60.1).

FIGURE 60.1. Midsagittal section of the neck shows the
fascia and spaces of the neck.



FIGURE 60.2. Cross-section of the neck at the thyroid
level.



TABLE 60.1. CERVICAL FASCIA



The superficial cervical fascia extends from its superior attachment on the zygomatic
process down to the thorax and axilla. It is composed of a continuous sheath of fatty
subcutaneous tissue similar to subcutaneous tissue elsewhere in the body except that it
ensheathes the platysma muscle and voluntary muscles of expression in the face. The
space between the superficial cervical fascia and deep cervical fascia contains superficial
lymph nodes, nerves, and vessels, including the external jugular vein. The superficial
cervical fascia is of minor importance in deep neck infections, and involvement of the
superficial space usually is managed successfully with local incision and drainage
combined with oral antibiotics (9).
Although the three layers of the deep cervical fascia are not histologically separate, these
classic anatomic divisions aid in understanding clinical patterns. The variable
terminology and descriptions in the literature have caused confusion. The superficial
layer of the deep cervical fascia, the middle layer of the deep cervical fascia, and the
deep layer of the deep cervical fascia are the preferred names for each layer (8). The
following descriptions of the fascial layers and spaces are based on the excellent
summaries by Levitt (3,7,8).
The superficial layer of the deep cervical fascia, also known as the enveloping or
investing layer, completely surrounds the neck. It extends from its insertion at the nuchal
line of the skull to the chest and axillary region. It spreads anteriorly to the face and
attaches to the clavicles. This continuous fibrous tissue sheath envelops the
sternocleidomastoid and trapezius muscles and the parotid and submandibular glands
(3,7,8).
The middle layer of the deep cervical fascia is best understood as two divisionsthe
muscular division and the visceral division. The muscular division forms a continuous
sheath below the superficial layer of the deep cervical fascia and surrounds the strap
muscles. It attaches superiorly to the hyoid bone and thyroid cartilage and inferiorly to
the sternum, clavicle, and scapula. The visceral division is so named because it surrounds
the anterior viscera of the neckthyroid gland, trachea, and esophagus. The
posterosuperior origin is the base of the skull posterior to the esophagus, and its
anterosuperior attachment is at the thyroid cartilage and hyoid bone. It continues
inferiorly into the thorax, covers the trachea and esophagus, and blends with the fibrous
pericardium. The buccopharyngeal fascia is a portion of the visceral division posterior to
the pharynx that covers the constrictor muscles and buccinator muscles (3,7,8).
The deep layer of the deep cervical fascia forms a complete ring with the great vessels
outside the ring and the phrenic nerve inside the ring. The deep layer is divided into the
prevertebral and alar divisions. The prevertebral division begins immediately anterior to
the vertebral bodies, spreads laterally to fuse with the transverse processes, and extends
posteriorly to enclose the deep muscles of the neck. It sends septa out between these
muscles and attaches to the vertebral spines posteriorly. Extending from the base of the
skull to the coccyx, the prevertebral division forms the posterior wall of the danger space
and the anterior wall of the prevertebral space. The alar division lies between the
prevertebral division and the middle layer of the deep cervical fascia. It courses from
transverse spinous processes on one side to the contralateral transverse processes and
extends from the base of the skull to the second thoracic vertebra, where it fuses with the
visceral fascia of the middle layer of the deep cervical fascia. The alar division completes
the posterolateral portion of the retropharyngeal space and contributes to the anterior wall
of the danger space (3,7,8). All three layers of the deep cervical fascia are involved in
formation of the carotid sheath, which runs from the base of the skull through the
pharyngomaxillary space and along the deep layer of the deep cervical fascia into the
chest.
ANATOMY OF DEEP NECK SPACES
The deep cervical fascia separates the neck into a series of potential spaces (Fig. 60.3,
Fig. 60.4). Although this division is clinically important, the spaces communicate with
one another. Because the spread of infection follows the route of least resistance,
predictable patterns of extension have been described (Fig. 60.5) (9). The potential spaces
of the neck are classified according to their relation with the hyoid bone, as shown in
Table 60.2 (8). Great confusion can arise concerning the multiple synonymous terms
given to the neck spaces. To avoid this, the common names for each space are provided.

FIGURE 60.3. Cross-section of the neck at the level of
the oropharynx shows the anatomic relations of the deep
neck spaces. 1, Pharyngomaxillary space; 2, visceral
vascular space; 3, retropharyngeal space; 4, danger space;
5, prevertebral space; AD, alar division of deep layer; PD,
prevertebral division of deep layer.



FIGURE 60.4. Oblique section through the neck shows
the anatomic relations of the spaces limited to above the
hyoid bone to the spaces that traverse the entire neck. The
important relation between the parapharyngeal
(pharyngomaxillary) space and the other spaces is
evident. (Modified from ref. 8, with permission.)



FIGURE 60.5. Network of patterns of infectious
extension within the potential spaces of the neck. PMS,
Pharyngomaxillary space; VVS, visceral vascular space.



TABLE 60.2. DEEP NECK SPACES



Spaces Involving Entire Length of Neck
Retropharyngeal Space
The retropharyngeal space is the potential space between the visceral division of the
middle layer of the deep cervical fascia, which surrounds the pharynx and esophagus
anteriorly, and the alar division of the deep layer of the deep cervical fascia posteriorly.
Also known as the retrovisceral, retroesophageal, and posterior visceral space, it
extends from the base of the skull inferiorly to the level of the first or second thoracic
vertebra, where the visceral and alar layers fuse. The retropharyngeal nodes are contained
within this space and separated into two lateral chains by the midline raphe. The raphe
forms where the superior constrictor muscle adheres to the prevertebral division of the
deep layer of the deep cervical fascia (3,7,8).
Danger Space
The danger space is a potential space between the alar and prevertebral divisions of the
deep layer of the deep cervical fascia. It is posterior to the retropharyngeal space and
anterior to the prevertebral space. It has earned this name because it extends from the
base of the skull into the posterior mediastinum to the level of the diaphragm and offers
little resistance to the spread of infection. The alar and prevertebral divisions of the fascia
fuse with the vertebral transverse processes to limit the space laterally (3,7,8).
Prevertebral Space
The prevertebral space is the compact potential space anterior to the vertebral bodies and
posterior to the prevertebral division of the deep cervical fascia. It extends from the base
of the skull to the coccyx. Lying just posterior to the danger space, it is limited laterally
by the fusion of the prevertebral division of the deep cervical fascia with the transverse
processes of the vertebra (3,7,8).
Visceral Vascular Space
The visceral vascular space is the potential space within the carotid sheath. It contains the
carotid artery, the internal jugular vein, and the vagus nerve (cranial nerve X). Because
this compact space contains little areolar connective tissue, infection remains relatively
localized. The lymphatic vessels within this space receive secondary drainage from most
of the lymphatic vessels of the head and neck. Because all three layers of the deep
cervical fascia contribute to the carotid sheath, Mosher in 1929 called this fascia the
Lincoln Highway of the neck (3,7,8). (The Lincoln Highway was the first paved
transcontinental highway in the United States.)
Spaces Limited to Above the Hyoid Bone
Pharyngomaxillary Space
The pharyngomaxillary space, also known as the lateral pharyngeal, parapharyngeal, or
peripharyngeal space, is analogous to an inverted cone lying in the lateral aspect of the
neck. The base is situated superiorly at the base of the skull, and the apex inferiorly at the
hyoid bone. The medial border is the lateral pharyngeal wall, and the lateral border is the
superficial layer of the deep cervical fascia over the mandible, internal pterygoid muscle,
and parotid gland. The pterygomandibular raphe and prevertebral fascia, respectively,
form the anterior and posterior limits (3,7,8).
Submandibular Space
The submandibular space is composed of the sublingual space superiorly and the
submaxillary space inferiorly, divided by the mylohyoid muscle. The entire compartment
lies between the mucosa of the floor of the mouth above and the superficial layer of the
deep cervical fascia below. The mandible forms an inflexible anterior and lateral
boundary, the hyoid bone limits the inferior aspect, and the intrinsic muscles of the base
of the tongue compose the posterior border. The sublingual space contains the sublingual
gland, the hypoglossal nerve, and the Wharton duct. The submaxillary space is
subdivided by the anterior bellies of the digastric muscles into a central compartment, the
submental compartment, and two lateral compartments, the submaxillary compartments.
All these divisions freely communicate because the submaxillary (submandibular) gland
extends from the submaxillary space around the posterior border of the mylohyoid
muscle into the sublingual space to provide a direct communication for spread of
infection. Infection spreads freely beyond the limiting belly of the digastric muscle from
the submental to the submaxillary compartments (3,7,8).
Parotid Space
The superficial layer of the deep cervical fascia splits around the parotid gland and its
associated lymph nodes to form the parotid space. The fascia is an incomplete enclosure
that does not cover the upper inner surface of the gland, resulting in direct
communication with the pharyngomaxillary space. The external carotid artery, posterior
facial vein, and facial nerve transverse this space (3,7,8).
Masticator Space
The masticator space contains the masseter and pterygoid muscles, ramus and body of the
mandible, temporalis tendon, inferior alveolar vessels, and nerves. It is anterior and
lateral to the pharyngomaxillary space and inferior to the temporal space. The superficial
layer of the deep cervical fascia splits around the mandible to form this potential space
and encase the muscles of mastication (3,7,8).
Peritonsillar Space
The palatal tonsil forms the medial border of the peritonsillar space and the superior
constrictor muscle is the lateral margin. The anterior and posterior tonsillar pillars form
the superior, inferior, anterior, and posterior limits.
Temporal Space
The temporal space is between the temporalis fascia laterally and the periosteum of the
temporal bone medially. The temporalis muscle divides the space into superficial and
deep compartments. The internal maxillary artery is contained within this space (3,7,8).
Space Limited to Below the Hyoid Bone: Anterior Visceral Space
The anterior visceral space, often called the pretracheal space, lies in the anterior aspect
of the neck from the thyroid cartilage down to the superior mediastinum at the level of
the fourth thoracic vertebra, near the arch of the aorta. Enclosed by the visceral division
of the middle layer of the deep cervical fascia, the anterior visceral space begins just deep
to the strap muscles, completely surrounds the trachea, and reaches the anterior wall of
the esophagus (3,7,8).
BACTERIOLOGY
A wide array of organisms are found in abscesses of the deep neck spaces (Table 60.3).
Most abscesses contain mixed bacterial flora; in one study, an average of more than five
species were isolated in each case (10). Because the portal of entry and the likely
causative organism differ for each potential space, the findings of these studies may
reflect the distribution of spaces involved with infection in the particular survey rather
than of the true bacteriologic composition of generalized deep neck infections.
Streptococcus organisms, predominantly S. viridans and -hemolytic streptococci, and
staphylococci are frequent aerobic pathogens, particularly in abscesses among persons
who abuse intravenous drugs. Other aerobic isolates include diphtheroid bacteria and
Neisseria, Klebsiella, and Haemophilus organisms (5,10).

TABLE 60.3. BACTERIOLOGY



The presence of anaerobic organisms is likely to be underestimated during bacteriologic
studies because of the difficulty of culturing them. Most abscesses of odontogenic origin
involve anaerobic pathogens, and species of Bacteroides, predominantly B.
melaninogenicus, and Peptostreptococcus are common isolates (1,4). Eikenella
corrodens, which is often resistant to clindamycin, and Fusobacterium organisms are less
common, and B. fragilis is a rare isolate (5). The presence of a foul-smelling drainage
strongly suggests anaerobic involvement, but the absence of such as discharge does not
exclude the presence of anaerobic organisms (10). The percentage of -lactamase
producing aerobic and anaerobic organisms isolated from these infections is increasing,
which may have important consequences for antibiotic coverage.
DIAGNOSIS
The diagnosis of infection of the deep spaces of the neck has become more complex since
the introduction of antibiotics. Studies have shown that one half of patients have received
some form of antibiotic as an outpatient before returning with a deep neck abscess (11).
Local signs, such as edema, fluctuation, and pointing of an abscess, can be reduced.
Systemic symptoms often are masked (1), which can result in a missed or delayed
diagnosis and otherwise avoidable complications. Presentation, such as localized
symptoms, septic shock, or mediastinitis, depends on the degree of progression of the
disease (5). Fever, pain, and swelling are the most common presenting symptoms (Table
60.4). In one series the duration of these symptoms ranged from 12 hours to 28 days
(average, 5 days) (11).

TABLE 60.4. DIAGNOSIS SYMPTOMS AND
PHYSICAL FINDINGS OF DEEP NECK
INFECTIONS



Physical examination confirms the presence of swelling and elevated temperature among
most patients (Table 60.4). Thorough evaluation typically shows dehydration and other
findings related to compromise of the upper aerodigestive tract, such as odynophagia,
dysphagia, or trismus (5,11). Because of the growing incidence of infection of the deep
spaces of the neck caused by intravenous drug abuse, physical examination should
include a survey of the extremities and groin area for scarring from previous injections
(4). Horner syndrome, consisting of ipsilateral ptosis, miosis, and facial anhidrosis, can
be caused by infection in proximity to the sympathetic chain.
Plain lateral and anteroposterior radiographs of the neck are useful in the diagnosis of
infection of the deep spaces of the neck. Radiographic findings, such as foreign bodies,
tracheal deviation, subcutaneous air, fluid within the soft tissues or soft-tissue edema,
suggest infection or an abscess (Fig. 60.6, Fig. 60.7). Equally important are radiographs
of the chest, which may show pulmonary edema, pneumothorax, pneumomediastinum, or
hilar adenopathy.

FIGURE 60.6. Frontal plain radiograph of a patient with
early neck infection and a history of intravenous drug
abuse. Needle fragment (arrow) is evident.



FIGURE 60.7. Lateral plain radiograph of a child with a
retropharyngeal abscess shows thickening of the
retropharyngeal soft tissue, loss of normal curvature of
the cervical spine, and air (arrow) in the retropharyngeal
space.



If the clinical presentation or plain radiographs suggest the diagnosis of deep neck
infection, computed tomography (CT) is indicated. It provides better resolution, helps to
differentiate cellulitis from abscess, and clearly depicts the spaces involved and the
inferior extent of the process. The CT characteristics of an abscess in the deep neck
spaces include low attenuation (low Hounsfield units), contrast enhancement of the
abscess wall, tissue edema surrounding the abscess, and a cystic or multiloculated
appearance (Fig. 60.8) (12). Although it is the best study, CT does not always accurately
differentiate abscess from cellulitis. Definitive differentiation between cellulitis and
abscess often necessitates needle aspiration or surgical drainage. Magnetic resonance
imaging is not routinely indicated. Ultrasound is noninvasive and is less expensive than
CT. It may be useful for supplementing clinical examination for patients with soft-tissue
inflammation and can guide needle aspiration.

FIGURE 60.8. Computed tomographic scan of a patient
with an extensive abscess of the pharyngomaxillary
space. Air-fluid interphase, low-attenuation abscess
center, contrast enhancement of the abscess wall,
loculated appearance, and surrounding tissue edema are
evident.



MANAGEMENT
Securing and maintaining an adequate airway must be the first objectives of the physician
caring for a patient with infection of the deep spaces of the neck. Most patients need only
humidified oxygen and close observation. If an artificial airway is necessary,
endotracheal intubation can be difficult because the abscess distorts or obstructs the upper
airway. If intubation is not possible, tracheotomy or cricothyrotomy is performed. The
physician needs to remember that the surgical planes can be distorted and the trachea
deviated. After the airway is secure, therapy is aimed at controlling the infection and
preventing complications. Hospitalization is almost always indicated. Hospital stays
average more than 11 days for adults but are shorter for children (11).
Specimens for blood culture are obtained, needle aspiration of the abscess for culture is
performed, and parenteral antibiotics are administered. The antibiotic chosen should
cover the common pathogens. These infections usually are polymicrobial (gram negative,
gram positive, aerobic, and anaerobic), and both aerobic and anaerobic bacteria have
increased -lactamase production. Thus therapy with ampicillin-sulbactam or
clindamycin with a third-generation cephalosporin such as ceftazidime is begun pending
culture results (13). Empiric use of an antistaphylococcal penicillin is indicated when an
abscesses is thought to be of salivary gland origin. Fluid resuscitation often is indicated.
For most patients, medical therapy alone is inadequate, and surgical drainage is necessary
(3).
Surgical drainage is indicated for patients with abscesses or impending complications and
those whose condition does not improve after 48 hours of therapy with parenteral
antibiotics. The primary space involved and any additional spaces to which the abscess
has spread must be opened and drained. Because the surgical anatomic relations often are
distorted by inflammation and edema, the bony and muscular landmarks described by
Mosher in 1929 are useful guides for the surgeon (14). These landmarks include the tip of
the great horn of the hyoid bone in the lateral aspect, the cricoid cartilage in the midline,
and the styloid process at the base of the skull. The anterior border of the
sternocleidomastoid muscle and the posterior belly of the digastric muscle are valuable
muscular landmarks. Successful surgical therapy depends on good visualization, adequate
vascular control, wide incision, and open drainage.
Needle aspiration is an accepted method for obtaining material for culture. Herzon (15)
described the therapeutic use of needle aspiration of abscesses of the deep neck spaces.
One aspiration procedure on small abscesses or placement of indwelling catheters to
allow repeated aspiration of larger abscesses are alternatives to surgical incision and
drainage (15,16). Figure 60.9 is an algorithm for management of deep neck infection.

FIGURE 60.9. Algorithm for management of deep neck
infection. Antibiotics should be changed, if necessary,
according to culture results.



COMPLICATIONS
Complications attributable to deep neck infections continue to occur despite effective
diagnostic techniques, widespread availability of potent antibiotics, and accepted surgical
intervention (Table 60.5). These unfortunate and often avoidable occurrences most
commonly are caused by a delay in diagnosis and extension of the infection beyond the
primary space involved. Within the interconnected network of the cervical fascia lie
important neurovascular structures, including the carotid arteries, internal jugular veins,
sympathetic chain, and cranial nerves IX through XII. Spread of infection to the carotid
sheath can erode the carotid or cause thrombosis of the internal jugular vein. Hemorrhage
can be heralded by bleeding from the external auditory canal. This ominous sign
mandates immediate surgical intervention. Angiography can be used to identify the
involved artery. Thrombosis of the internal jugular vein associated with oropharyngeal
infection has been given the eponym Lemierre syndrome. This disorder usually is caused
by the anaerobe Fusobacterium necrophorum and is heralded by spiking fevers,
tenderness of the sternocleidomastoid muscle, neck stiffness, and metastatic abscesses
typically to the lung, but septic arthritis also is common. Retrograde thrombophlebitis can
lead to cavernous sinus thrombosis. The diagnosis is confirmed with the CT finding of
ring enhancement with central lucency in the internal jugular vein (Fig. 60.10). Treatment
is centered on antibiotics and surgical drainage of the abscess. Use of anticoagulants is
controversial. Lustig et al. (17) recommend ligation or excision of the vein for persistent
sepsis with embolism and anticoagulation for retrograde cavernous sinus thrombosis.

TABLE 60.5. COMPLICATIONS DEEP NECK
INFECTIONS



FIGURE 60.10. Computed tomographic scan of a patient
with Lemierre syndrome shows internal jugular vein
thrombosis (arrow) and ring enhancement of the internal
jugular vein with central lucency.



Patients with involvement of the sympathetic chain or cranial nerves may have Horner
syndrome or other neurologic deficits. Osteomyelitis of the mandible or cervical spine
can occur with infection of the associated deep neck spaces. Delay in treatment can cause
local complications or spread of infection beyond the neck.
One of the most dreaded complications of infection of the deep spaces of the neck is
mediastinitis. All patients with infection of the deep spaces of the neck are at risk of
mediastinitis. Chest radiographs are obtained to rule out a widened mediastinum,
pneumothorax, pneumomediastinum, or pulmonary edema. This descending necrotizing
mediastinitis must be differentiated from the less lethal form caused by esophageal
perforation. In a review of the literature from 1960 to 1980, Estrera et al. (2) found a
42.8% mortality rate, indicating that even the addition of antibiotics has not greatly
lowered mortality. The most important aspect of successful management of this disease is
early diagnosis and adequate drainage. Patients with mediastinal complications usually
have dyspnea, hypoxia, and increasing infectious symptoms. Computed tomography
typically shows the disease process clearly and facilitates rapid diagnosis (Fig. 60.11).
The initial neck scan is extended to include the chest if there is any evidence of possible
descending infection. In a review of the literature from 1960 to 1990, Wheatley et al. (18)
found transcervical mediastinal drainage to be inadequate in 79% of cases. Marty-Ane et
al. (19) recommended that all patients with mediastinitis undergo thoracotomy with
placement of several drainage tubes that can be irrigated with 0.5% povidone-iodine
solution.

FIGURE 60.11. Computed tomographic scans of a
patient with descending necrotizing mediastinitis. A:
Infection started in the submandibular spaces and spread
to the parapharyngeal and visceral vascular space. B: The
infection descended in the visceral vascular space and
invaded the anterior visceral (pretracheal) space. The
process reached the mediastinum through both the
anterior visceral (C) and visceral vascular (D) spaces.



Complications can occur during operations on patients with obscured surgical planes and
inflamed soft tissues. The surgeon must rely on fixed landmarks to minimize damage to
the neurovascular structures coursing in the deep neck spaces. Preoperative
administration of antibiotics and gentle manipulation of soft tissues decrease the
incidence of septicemia and wound infection. Undesirable scarring can be caused by
traditional placement of incisions for exposure rather than for cosmesis, leaving the
wound open for drainage, and diminished wound healing. When exposure is not
compromised, incisions can be placed along relaxed skin tension lines. Partial closure of
the incision is possible after adequate breakdown of loculation, irrigation, and drainage.
Scar revision techniques can be used after full recovery to augment appearance.
EMERGENCIES
All deep neck infections are managed as airway emergencies (Table 60.6). The expansion
of abscesses within the deep spaces of the neck can restrict air passage. Common
sequelae of deep neck infections include trismus, cervical rigidity, upper airway edema,
laryngotracheal deviation, and pain, all of which complicate intubation. Attempts at
intubation can perforate an abscess and cause aspiration of the purulent contents, damage
to the aerodigestive tract, or loss of the airway. Tracheotomy becomes more complex
when the anatomic planes are obscured and landmarks distorted. The appropriate
management of the airway differs with the individual deep neck spaces involved. Airway
emergencies often can be avoided if the physician recognizes the risk of airway
compromise. Patients with deep neck infections may have systemic infections and
symptoms ranging from mild fever to septic shock. Management of severe sepsis
includes timely institution of antibiotic therapy, fluid resuscitation, appropriate surgical
intervention, and administration of vasopressors. Involvement of the major vascular
structures that course in the deep neck spaces can cause hemorrhage or septic emboli,
which necessitate emergency intervention.

TABLE 60.6. EMERGENCIES DEEP NECK
INFECTIONS



SPECIFIC DEEP NECK INFECTIONS
Retropharyngeal Space Infections
The most common sources of infection of the retropharyngeal space are infections of the
nose, adenoids, nasopharynx, and paranasal sinuses that drain to the retropharyngeal
nodes. Because these nodes regress by the age of 4 or 5 years, most abscesses in the
retropharyngeal space occur among children. There often is a history of preceding acute
upper respiratory tract infection. Children may have fever, cervical adenopathy,
dysphagia, odynophagia, nuchal rigidity, and occasionally airway compromise. Because
of the distribution of the retropharyngeal nodes on either side of the midline fascial raphe,
bulging of the posterior pharyngeal wall to one side may be noticed. Among adults, pain,
dysphagia, snoring, noisy breathing, and limitations of cervical motion point to a
pharyngeal condition. Retropharyngeal abscesses in these patients can be caused by
instrumentation, a foreign body, or other trauma. Spread of tuberculosis or syphilis from
the cervical vertebrae has become rare but must be excluded.
The findings on lateral soft-tissue radiographs of the neck confirm the diagnosis.
Characteristic radiographic findings include abnormal thickening of the prevertebral soft
tissue, reversal of the normal cervical spine curvature, air in the prevertebral soft tissue,
and erosion of the associated vertebral body (Fig. 60.7). At the second cervical vertebra,
posterior pharyngeal soft tissue thicker than 7 mm is abnormal. At the sixth cervical
vertebra, tissue thicker than 22 mm in adults or 14 mm in children is abnormal. Soft-
tissue swelling in the posterior pharyngeal region greater than 50% of the width of the
vertebral body necessitates complete evaluation. True lateral neck radiographs must be
taken in extension and inspiration. False-positive radiographic findings may appear on
oblique radiographs whereby trapped pharyngeal air can be mistaken for retropharyngeal
gas. During flexion, the retropharyngeal soft tissues bow into the airway. Crying,
swallowing, or expiration can cause transient rostral displacement of mediastinal
structures and temporarily thicken the retropharyngeal space. Computed tomography can
aid in diagnosis in questionable cases and delineate the extent of the abscess.
Surgical drainage is considered the mainstay of therapy, but as diagnostic and culture
techniques improve and antibiotics become more sophisticated, many patients can be
treated successfully without surgical intervention. The physician must secure an adequate
airway. If emergency airway control becomes necessary, tracheotomy is considered
because intubation risks perforation of the abscess and subsequent aspiration.
Tracheostomy rarely is needed. Abscesses localized to the parapharyngeal space usually
are drained through a transoral approach to avoid visible scarring and contamination of
the tissue planes in the neck. A surgeon using this approach must protect the airway from
aspiration by placing the patient in the Rose position with the neck in extreme extension
and the vertex of the head dependent. External approaches are used to manage abscesses
involving other deep neck spaces (20).
Infection in the retropharyngeal space can extend into the anterior or posterior
mediastinum and necessitate drainage by means of external thoracotomy. Such extension,
characterized by severe dyspnea, chest pain, persistent fever, and a widened mediastinum
on a chest radiograph, is a serious complication that has a high mortality. Adjacent spaces
susceptible to infectious spread from the retropharyngeal space include the danger space
and the pharyngomaxillary space.
Danger Space Infections
Involvement of the danger space is caused by infectious spread from the retropharyngeal,
pharyngomaxillary, and prevertebral spaces or, more rarely, by lymphatic extension from
the nose and throat. The infection spreads rapidly through the loose areolar tissue within
this space to the posterior mediastinum and thorax. At first, patients have only signs and
symptoms of the primary space involved. Later, their condition becomes toxic, and the
findings are those of mediastinitis or empyema. Treatment consists of drainage as
described for infections of the retropharyngeal space and intravenous antibiotics with
thoracotomy for mediastinal spread.
Prevertebral Space Infections
Before antibiotics were available, infection of the prevertebral space commonly was
caused by pyogenic or tuberculous involvement of the vertebral bodies. Penetrating
trauma, including iatrogenic trauma, now is the most common cause. The resurgence of
tuberculosis, including aggressive manifestations among persons with acquired
immunodeficiency syndrome, can increase this relatively rare diagnosis. Infection of this
space can cause vertebral osteomyelitis and spinal instability. The presentation is similar
to that of infections of other posterior spaces involving the entire length of the neck.
Therapy includes antibiotics, stabilization of the spine, and surgical drainage through an
external approach.
Visceral Vascular Space Infections
Infections of the visceral vascular space can complicate many infections of the head and
neck. Infections of the pharyngomaxillary space are the most common infection of the
deep spaces of the neck to spread to the visceral vascular space, but the risk exists for
spread from any deep neck space. Complications of involvement of this space, such as
thrombosis of the internal jugular vein or carotid rupture, are discussed earlier.
Pharyngomaxillary Space Infection
The pharyngomaxillary or parapharyngeal space connects to every other major fascial
space and thus occupies an important position in the neck. Infections originating in the
parotid, masticator, peritonsillar, or submandibular spaces can reach this space and move
to the retropharyngeal space and into the chest. Infections originating in this space
usually are caused by spread from the tonsils and pharynx, although occasionally the
primary infection has resolved by the time the parapharyngeal infection manifests itself.
Local invasion from other portals of entry include odontogenic sources and the lymph
nodes that drain infections of the nose and throat (16). Mastoiditis with bony destruction
in the mastoid tip can extend to this space (Bezold abscess).
The pharyngomaxillary space is divided into the anterior and posterior compartments by
the styloid process and its muscles. The prestyloid or anterior compartment, also known
as the muscular compartment, contains no vital structures, but it is closely related to the
tonsillar fossa medially and the internal pterygoid muscle laterally. Infection in the
anterior compartment typically manifests as displacement of the lateral pharyngeal wall
in the tonsillar area and early trismus. The retrostyloid or posterior compartment is
traversed by the carotid sheath, cervical sympathetic chain, and cranial nerves IX through
XII and is known as the neurovascular compartment. Posterior space involvement, which
can cause serious neurovascular complications, typically manifests late in the course with
swelling of the posterior tonsillar pillar area and minimal trismus. If the infection
involves both compartments, a combination of symptoms occurs.
Most patients have edema, sore throat, and odynophagia. Swelling in the neck can be
caused by inferior extension to the lower limit of the hyoid bone. Successful therapy
includes airway maintenance, parenteral antibiotics, and surgical drainage. External
drainage is through the submaxillary fossa as described by Mosher (14) in 1929. A T-
shaped incision is made with the horizontal limb parallel to and below the body of the
mandible and the vertical limb along the anterior border of the sternocleidomastoid
muscle. An alternative is to make the more cosmetic horizontal incision alone. The
surgeon follows the carotid sheath to find the abscess cavity within the
pharyngomaxillary space. The surgeon's finger is inserted below the submandibular gland
and used to dissect bluntly along the posterior belly of the digastric muscle deep to the
mastoid tip toward the styloid process, which lies within the pharyngomaxillary space.
Separate drains are placed in the superior and inferior portions of the opened space. The
tip of the greater cornu of the hyoid bone is an important fixed inferior landmark.
Because of the important neurovascular structures that traverse the pharyngomaxillary
space, serious complications of abscesses can occur in this area, including thrombosis of
the internal jugular vein (Lemierre syndrome) and carotid rupture. Neurologic sequelae
can be caused by involvement of cranial nerves IX through XII or the sympathetic chain.
Submandibular Space Infection
In 1836 Wilhelm von Ludwig (21), a German surgeon, described repeated recent
occurrences of a certain type of inflammation of the throat, which, despite the most
skillful treatment, is almost always fatal. He was referring to the rapidly spreading,
potentially fatal infections involving the submandibular space that now bear his name.
The mortality rate for Ludwig angina historically was more than 50%, but with
widespread use of antibiotics and timely surgical intervention, the mortality has fallen to
less than 5% (22).
Since the use of antibiotics became widespread, an increasing percentage of infections of
the submandibular space is caused by infections of the submandibular gland or
submandibular nodes, but about 70% continue to be caused by dental or periodontal
disease (22). Infections originating in a position anterior to the second molar drain
initially through the inner cortex of the mandible into the sublingual space. Infections of
the last two molars can drain into the submandibular space because the mylohyoid
muscle inserts more rostrally on the posterior aspect of the mandible. Early
manifestations include involvement of the oral tissue near the dental origin and tender
swelling of the sublingual and submental area. If the patient is not treated, the process
progresses to severe cellulitis with a board-like firmness of the floor of the mouth and
brawny induration of the suprahyoid soft tissue characteristic of Ludwig angina. In true
Ludwig angina, all the sublingual and bilateral submaxillary spaces are involved. Patients
may have swelling in the submaxillary area associated with severe pain, drooling,
trismus, dysphagia, and difficulty breathing. The tongue is displaced posteriorly and
superiorly against the palate, ultimately with respiratory embarrassment.
Therapy with intravenous antibiotics can be curative if begun early in the disease.
Because of the likelihood of odontogenic origin, anaerobic coverage is provided. Rapid
surgical intervention is imperative if there is increasing airway obstruction, localized
abscess with fluctuation, or failure to improve with antibiotics. A horizontal submental
incision just above the hyoid bone is carried down through the platysma. The deep
cervical fascia and mylohyoid muscle are incised vertically from symphysis to hyoid
bone. If the patient has Ludwig angina, a straw-colored, weeping exudate, rather than true
abscess fluid, is released.
Drains are placed in a position deep to the mylohyoid muscle well within the sublingual
space. Prevention of airway obstruction must be the primary concern of physicians caring
for patients with infections of the submandibular space. Patients with trismus, an
indurated neck, displaced tongue, glottic edema, or pharyngeal edema have formidable
airway problems. Orotracheal intubation often is difficult for these patients because
swelling of the floor of the mouth and trismus limit visualization. Awake blind nasal
intubation can precipitate obstruction among patients with a vulnerable airway and can
cause laryngeal trauma. Infection that has spread to the pharyngomaxillary or
retropharyngeal space can cause rupture with aspiration of pus.
Fiberoptic intubation is performed only by experienced, skilled anesthesiologists when
the patient is atypically cooperative and in stable condition. If establishment of an
artificial airway is indicated, the patient is taken to the operating room, and sterile
preparation for tracheotomy is begun with the surgeons scrubbed and a tracheostomy set
available before any attempts at intubation are made. No narcotics are given because they
can exacerbate respiratory difficulty. Some physicians advocate inhalation anesthesia to
relieve pain and muscle spasms and allow the patient's mouth to be open and the larynx
visualized for intubation (22). Elective tracheotomy under local anesthesia is acceptable
to secure the airway; however, the surgeon must remember that the infection might have
spread to the lower neck, making tracheotomy technically difficult. A nasal airway
occasionally can be passed beyond the posterior pharyngeal edema to temporarily secure
the airway. Ludwig angina is more likely to necessitate tracheotomy than other infection
of the deep spaces of the neck (4).
Masticator Space Infections
Most infections of the masticator space have a dental origin, typically from the molars.
Extreme trismus is caused by irritation and spasm of the encased muscles of mastication.
There may be swelling over the ramus of the mandible and posterior floor of mouth.
Spread to other spaces and the associated symptoms can occur. Treatment includes
judicious airway management, intravenous antibiotics, and usually surgical drainage.
Drainage is performed through an incision below the mandible and carried down to the
periosteum. Blunt dissection is performed in a plane superficial and deep to the mandible.
Delay in diagnosis can cause osteomyelitis of the mandible.
Peritonsillar Space Infections
Infections of the peritonsillar space are the most common suppurative infections
involving the juxtapharyngeal spaces. Involvement of this space is caused by extension of
infection in the tonsillar fossa and typically occurs among adolescents and young adults.
Trismus, painful swelling in the throat, swallowing difficulties, fever, and otalgia are
common symptoms. Physical examination shows that the patient's condition appears
toxic and that the patient has a hot potato voice and drooling. Unilateral swelling of the
peritonsillar area with bulging of the soft palate and deviation of the midline of the palate
and uvula to the contralateral side are classic findings. Tonsillar erythema and exudate
can be severe or surprisingly mild. The diagnosis often is made on clinical grounds and
confirmed with needle aspiration of the suspected abscess. Ultrasonography and CT are
more specific and sensitive than clinical examination alone in the detection of
peritonsillar abscess (23). Abscesses of the pharyngomaxillary space can mimic
peritonsillar abscesses. Because abscesses of the pharyngomaxillary space are drained
externally, CT is performed to differentiate these diseases when the diagnosis is unclear.
Management of peritonsillar abscess (quinsy) is controversial. Options include needle
aspiration, incision and drainage, or immediate tonsillectomy (quinsy tonsillectomy).
Needle aspiration and incision and drainage are effective more than 90% of the time and
have the same efficacy for some but not all practitioners. Both procedures place the
patient at risk of recurrent peritonsillar abscess. The overall risk of recurrent abscess is
approximately 10% to 15%; however, patients younger than 40 years with a history of
recurrent tonsillitis are at the greatest risk (24). Schechter et al. (25) believe that only
patients with a history of previous peritonsillar abscess or chronic tonsillitis should be
considered for interval tonsillectomy.
Incision and drainage or aspiration can be accomplished after application of topical and
infiltrative anesthesia. The area of maximum fluctuance, usually the superior pole, is
incised or aspirated with an 18-gauge spinal needle. Whereas most abscesses are located
in the superior pole, some are midtonsillar or at the inferior pole. After incision, the
abscess cavity is opened widely with a long hemostat. Normal findings at exploration
precipitate an inferior search. Incision and drainage of a peritonsillar abscess often is
poorly tolerated by adults and children alike and occasionally necessitates general
anesthesia. The choice of antibiotics is controversial, but penicillin or clindamycin are
routinely used after abscess drainage. After intraoral drainage, many patients can be
treated as outpatients. Those with dehydration, debility, immunosuppression, or sepsis or
who have potentially unstable airways are admitted for therapy with intravenous fluids,
parenteral antibiotics. and close observation. For the rare case that fails to resolve with
drainage and antibiotics, some surgeons advocate tonsillectomy. An inadequate or
misplaced incision is the most likely reason for failed resolution with drainage and
antibiotics, and tonsillectomy certainly ensures adequate drainage. Extension to the
pharyngomaxillary space must be excluded. If present, this space must be drained
externally (Fig. 60.12).

FIGURE 60.12. Computed tomographic scan of a patient
with a peritonsillar abscess (triangle) shows cellulitis of
the parapharyngeal space (arrow). Every peritonsillar
abscess is a potential parapharyngeal abscess that can
lead to mediastinitis.



Temporal Space Infection
Patients with infections of the temporal space have pain in the area of the temporalis
muscle with associated trismus and occasionally deviation of the jaw to the affected side.
They are treated with external drainage through an incision approximately 3 cm posterior
to the lateral canthus or a horizontal brow incision. The superficial and deep
compartments must be drained. Most patients can be treated as outpatients with oral
antibiotics after incision.
Anterior Visceral Space Infection
Most infections in the anterior visceral space are caused by perforations of the anterior
esophageal wall during instrumentation, a foreign body, or external trauma. Infections
rarely spread from the thyroid gland or other deep neck spaces. Patients with anterior
visceral space infections initially report swallowing difficulties. As the infection
progresses, it can cause hoarseness, dyspnea, and airway obstruction. Laryngoscopy may
show swelling and erythema of the hypopharyngeal wall, and palpation of the neck may
show crepitus from subcutaneous emphysema. Therapy consists of intravenous
antibiotics, nasogastric suction, and external drainage. If the abscess is well localized, an
incision over the area of pointing may suffice. If the abscess is not localized, a wider
incision is necessary. These patients are treated aggressively and observed closely
because of the high risk of airway compromise and mediastinitis.

HIGHLIGHTS
Odontogenic sources are the most common origin of deep neck
infections and typically involve anaerobic pathogens.
Staphylococcal infections of the salivary gland also are frequent
sources.
Intravenous drug abuse has become an increasingly common
cause of deep neck infection. The vascular space containing the
carotid artery is especially vulnerable.
Commonly sequelae of deep neck infections, including trismus,
cervical rigidity, upper airway edema, laryngotracheal
deviation, and pain, make intubation difficult. If an artificial
airway becomes necessary, tracheotomy or cricothyroidotomy
is considered. It is important to remember that the surgical
planes can be distorted and the trachea deviated.
Surgical drainage is indicated for abscesses of the deep neck
space, for impending complications, and for lack of
improvement after 48 hours of parenteral antibiotic therapy.
Successful surgical therapy depends on good visualization,
adequate vascular control, wide incision, and open drainage.
The primary abscess space and secondarily involved spaces
must be opened and drained.
Mediastinitis, characterized by severe dyspnea, chest pain,
persistent fever, and evidence of a widened mediastinum on a
chest radiograph, can occur by means of extension of deep neck
infections.
Ludwig angina is infection of the submandibular space
characterized by a boardlike firmness of the floor of mouth,
posterosuperior displacement of the tongue, drooling, and rapid
airway compromise. Patients need immediate surgical
intervention with wide incision of the submental deep cervical
fascia and insertion of drains deep to the mylohyoid muscle.
Because the anatomic relations are distorted by inflammation
and edema, safe surgical intervention must rely on fixed
surgical landmarks, including the tip of the great horn of the
hyoid bone, the cricoid cartilage, and the styloid process.
Surgical approaches to external drainage are based on
identification of the carotid sheath, which is followed to the
abscesses, opening potential spaces along the path.
Local signs of deep neck infection, such as edema, fluctuation,
and pointing of an abscess, can be reduced and systemic
symptoms masked by antibiotics, causing the diagnosis to be
missed or delayed and otherwise avoidable complications.
Signs and symptoms of peritonsillar abscess include trismus,
dysphagia, drooling, fever, a hot potato voice, deviation of
the midline palate and uvula, and bulging of the posterolateral
soft palate.
CHAPTER REFERENCES
1. Blomquist IK, Bayer AS. Life-threatening deep fascial space infections of the head and neck.
Infect Dis Clin North Am 1988;2:237264.
2. Estrera AS, Landay MJ, Grisham MJ, et al. Descending necrotizing mediastinitis. Surg Gynecol
Obstet 1983;157:545552.
3. Levitt GW. The surgical treatment of deep neck infections. Laryngoscope 1971;81:403411.
4. Har-El G, Aroesty JH, Shaha A, et al. Changing trends in deep neck abscesses: a retrospective
study of 110 patients. Oral Surg Oral Med Oral Pathol 1994;77:446450.
5. Tom MB, Rice DH. Presentation and management of neck abscess: a retrospective study.
Laryngoscope 1988;98:877880.
6. Schloss MD, Taibah K, Nogrady MB. Third branchial cleft sinus route of infection in deep neck
abscesses. J Otolaryngol 1986;15:5658.
7. Levitt GW. Cervical fascia and deep neck infections. Laryngoscope 1970;80:409435.
8. Levitt GW. Cervical fascia and deep neck infections. Otolaryngol Clin North Am 1976;9:703716.
9. Paonessa DF, Goldstein JC. Anatomy and physiology of head and neck infections (with emphasis
on the fascia of the face and neck). Otolaryngol Clin North Am 1976;9:561580.
10. Bartlett JG, Gorbach SL. Anaerobic infections of the head and neck. Otolaryngol Clin North Am
1976;9:655678.
11. Gidley PW, Ghorayeb BY, Stiernberg CM. Contemporary management of deep neck space
infections. Otolaryngol Head Neck Surg 1997;116:1622.
12. Holt GR, McManus K, Newman RK, et al. Computed tomography in the diagnosis of deep neck
infections. Arch Otolaryngol 1982;108:693696.
13. Fairbanks DNF. Drugs of choice. In: Fairbanks DNF, ed. Pocket guide to antimicrobial therapy in
otolaryngology head and neck surgery, 8th ed. Alexandria, VA: AAO-HNS, 1996:68.
14. Mosher HP. The submaxillary fossa approach to deep pus in the neck. Trans Am Acad Ophthalmol
Otolaryngol 1929;34:1936.
15. Herzon FS. Needle aspiration of nonperitonsillar head and neck abscesses. Arch Otolaryngol Head
Neck Surg 1988;114:13121314.
16. de Marie S, Tham RT, van der Mey AGL, et al. Clinical infections and nonsurgical treatment of
parapharyngeal space infections complicating throat infections. Rev Infect Dis 1989;11:975982.
17. Lustig LR, Cusick BC, Cheung SW, et al. Lemierre's syndrome: two cases of postanginal sepsis.
Otolaryngol Head Neck Surg 1995;112:767772.
18. Wheatley MJ, Stiriling MC, Kirsch MM, et al. Descending necrotizing mediastinitis: transcervical
drainage is not enough. Ann Thorac Surg 1990;49:780784.
19. Marty-Ane CH, Alauzen M, Alric P, et al. Descending mediastinitis. J Thorac Cardiovasc Surg
1994;197:5561.
20. Choi SS, Vezina LG, Grundfast KM. Relative incidence and alternative approaches for surgical
drainage of different types of deep neck abscesses in children. Arch Otol Head Neck Surg
1997;123:12711275.
21. Ludwig WF, quoted in Burke J. Angina ludovic: a translation together with a biography of
Wilhelm F. von Ludwig. Bull Hist Med 1939;7:11151126.
22. Allen D, Loughnan TE, Ord RA. A re-evaluation of the role of tracheostomy in Ludwig's angina. J
Oral Maxillofac Surg 1985;43:436439.
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232.
24. Herzon FS. Peritonsillar abscess: incidence, current management practices, and a proposal for
treatment guidelines. Laryngoscope 1995;105[Suppl 74]:117.
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1982;92:657659.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

61 PRINCIPLES OF TRAUMA
Head & Neck SurgeryOtolaryngology
61




PRINCIPLES OF TRAUMA
PETER J. KOLTAI
PAUL H. KISPERT

P.J. Koltai: Section of Pediatric Otolaryngology, Cleveland Clinic Foundation, Cleveland, Ohio.
P.H. Kispert: Department of Surgery, Dartmouth Medical School, Lebanon, New Hampshire.


Neuroendocrine Response
Metabolic Response
Treatment of a Patient who has Sustained Trauma
Primary Survey
Secondary Survey
Definitive Management
Role of the Otolaryngologist
Chapter References
Trauma is a blight on our society. It is the leading cause of death and disability of
Americans younger than 40 years. In the United States, more than 150,000 violent deaths
occur each year, and more than 500,000 trauma victims are left with permanent
disabilities. Although it is difficult to know the total cost to society of this epidemic, it is
estimated that the annual cost of dealing with this national tragedy is more than $100
billion. In a 1999 study it was found that the average personal injury in the workplace
costs more than $8,000 in lost earnings (1). Trauma patients consume more health care
resources than heart and cancer patients combined, and whereas mortality from heart
disease and cancer is declining, the incidence of trauma is increasing (2,3).
Deaths from trauma fall into three categoriesimmediate, early, and late. Immediate
death occurs within minutes of the injury and is caused by acute airway obstruction and
major vessel disruptions of the brain, heart, and great vessels. Early death occurs in the
first few hours after injury and is associated with excessive hemorrhage, accumulation of
blood around the brain, and respiratory failure. Late death occurs days to weeks after
trauma and is caused by sepsis and multiple organ failure.
More than half the deaths due to trauma occur within several minutes of the accident.
Because on-the-spot therapy rarely is available, accident prevention is the most logical
way to decrease this number. Use of airbags, seat belts, and bicycle helmets have greatly
contributed toward this goal. Early deaths account for about one third of all trauma
deaths. Although not all of these patients can be saved, treatment of many can effective if
it is rapid and definitive. This requires a parallel system of prehospital care and hospital
care.
Among patients with head injury, death at the scene of the accident usually is caused by
hypoventilation due to loss of consciousness. Intubation in the field can thus be
lifesaving. Another common cause of prehospital death is massive hemorrhage. When
intravenous catheters are inserted at the scene, circulatory volume can be maintained until
the hemorrhage can be controlled surgically. Rapid transport to a hospital with an
organized team of surgeons, anesthesiologists, and trauma professionals is vital for the
effective treatment of trauma patients. In urban areas, ambulances usually provide
efficient transportation to the hospital. In rural areas, distance becomes a critical factor;
thus use of helicopters and airplanes can be lifesaving (1,2,3,4,5,6 and 7).
Trauma patients undergo rapid and severe changes in normal body function, including
hemorrhage, tissue hypoxia, cellular damage, and disrupted function of vital organs. The
physiologic response to massive injury is dramatic and occurs both systematically and
locally. Systemic responses include activation of the clotting sequence, shifts of
extravascular fluid into the circulatory system, redistribution of blood flow to the heart
and brain, and alterations in renal and pulmonary function to maintain acid-base balance.
Metabolic changes include the breakdown of skeletal muscle and fat to provide substrate
for the body's fuel-intensive response to trauma. Local responses include immunologic
activation with mobilization of leukocytes, synthesis of acute-phase proteins, migration
of inflammatory cells into the injured area, and the onset of fibroblast proliferation and
blood vessel ingrowth to begin the process of wound repair. Understanding of the
restorative mechanisms that occur in an acutely injured patient is necessary for the
complex task of treating these patients with regard to fluid maintenance, nutritional
requirements, wound healing, and susceptibility to infection (8,9).
NEUROENDOCRINE RESPONSE
Hemostatic adjustments to trauma are mediated by the neuroendocrine system. Stimuli
such as hemorrhage, hypoxia, and tissue damage stimulate a graded response that
increases to a peak level, after which additional response is no longer possible. Pain is the
first signal of the central nervous system (CNS) for the initiation of homeostasis. The
hypothalamic response to pain stimulates the pituitary gland to release corticotropin,
which stimulates adrenal secretion of cortisol. Pain causes elaboration of antidiuretic
hormone for conservation of fluid. Pain activates the sympathetic nervous system and
stimulates direct adrenal secretion of epinephrine.
Blood loss stimulates vascular pressure and volume receptors and precipitates a CNS-
mediated decrease in cardiac output, an increase in peripheral vascular resistance, and
redistribution of blood flow to the vital organs. Hypoxia and hypercapnia cause
chemoreceptor stimulation, vasomotor activation, and increased respiratory drive. At later
stages, stimulation of the hypothalamus by interleukin 1 initiates the hypermetabolic
response to injury manifested by the elevated temperatures experienced by injured
patients (6,7).
The hormonal response to trauma is marked by a rise in the catabolic hormones,
corticotropin, cortisol, growth hormone, glucagon, epinephrine, and norepinephrine. In
contrast, plasma concentrations of the primary anabolic hormone, insulin, are decreased
owing to CNS-mediated sympathetic inhibition of the pancreas. Posttraumatic
hyperglycemia provides non-insulin-mediated tissues such as the brain with a preferential
supply of glucose.
Glucagon, cortisol, and catecholamines maintain blood glucose levels and prevent
hypoglycemia. The primary function of glucagon, which is produced in the pancreas, is to
promote gluconeogenesis in the liver. After trauma, direct sympathetic stimulation of the
pancreas enhances secretion of glucagon. Release of corticotropin by the anterior
pituitary gland causes adrenal elaboration of cortisol, which promotes the breakdown of
skeletal muscle into amino acids and facilitates gluconeogenesis in the liver. The
hypoglycemic effect of cortisol counteracts insulin.
The hormonal reaction most fundamental to trauma is the release of catecholamines.
Epinephrine, released by the adrenal medulla in response to direct neurostimulation, is a
potent regulator of the circulatory system and systemic metabolism. The hemodynamic
effects of epinephrine include vasoconstriction, increased cardiac rate, and increased
myocardial contractility and conductivity. Epinephrine also promotes the production of
glucose by enhancing hepatic gluconeogenesis and inhibiting the release of insulin.
Norepinephrine, the primary neurotransmitter of the sympathetic nervous system, exerts a
direct effect on the circulatory system and vital organs. With massive and prolonged
sympathetic discharge, norepinephrine can enter the bloodstream and exert a direct
vasoconstrictive effect on the vascular system similar to that of epinephrine (8,9).
METABOLIC RESPONSE
The postinjury period is characterized by catabolism. Negative nitrogen balance,
hyperglycemia, and heat production reflect the increased energy requirements for
ongoing reparative and inflammatory processes. Increased energy expenditure is due to
sustained release of circulating catecholamines and increased activity of the sympathetic
nervous system. The primary source of energy during this period comes from oxidation
of lipids promoted by the elaboration of the catabolic hormones (8,9).
Although fat is the primary energy source after injury, protein also is broken down to
produce energy. In a fasting catabolic patient, glucose can be generated only from the
breakdown of protein. Lipid breakdown to triglycerides and glycerol contributes
minimally to form precursors for the synthesis for new glucose. As a result, protein is
rapidly broken down to form precursors for new glucose synthesis in a trauma patient in
the catabolic state. The result is rapid loss of muscle mass. The depth and the length of
the catabolic state are related to the severity of the trauma. Although it represents an
adaptive mechanism, a persistently prolonged and severe catabolic state leads to severe
malnutrition, multiple organ failure, and death (8,9,10,11 and 12).
TREATMENT OF A PATIENT WHO HAS SUSTAINED TRAUMA
The most important factors in the successful care of a trauma patient are the initial
evaluation and resuscitation performed in the emergency department. To facilitate a
rational approach to decision making in these difficult circumstances, the American
College of Surgeons has developed a protocol taught in advanced trauma life support
courses. It is based on a primary and secondary survey approach that allows physicians to
handle the complex, multisystem problems of trauma patients. This treatment algorithm
can be divided into four categoriesprimary survey, resuscitation, secondary survey, and
definitive care.
The primary survey involves hierarchical assessment of airway, breathing, and
circulation. The purpose is to identify extreme, life-threatening injuries and institute
immediate life-sustaining maneuvers. Resuscitation is performed simultaneously with the
primary survey. The secondary survey consists of a rapid but systematic head-to-toe
physical examination with the patient completely disrobed. This global assessment is
done to identify all potentially life-threatening and occult injures. An important part of
the secondary survey is radiographic assessment of the neck, chest, and pelvis. Samples
are drawn for baseline blood studies, typing, and cross-matching. Once these priorities
have been addressed, vital signs are rechecked. When the patient's condition is stable, a
detailed management plan is established.
Primary Survey
Airway
The foremost emergency measure is establishment of the airway, which may be lost to a
variety of causes. The oropharynx, larynx, and trachea can be obstructed by secretions,
blood, and foreign bodies. Collapse of the oropharyngeal airway can occur with loss of
consciousness and from facial fractures. Direct trauma to the larynx and trachea may
cause airway obstruction below the oropharynx. Maneuvers to secure an adequate airway
range from the simple to the complex and begins with manual cleaning of the oropharynx
followed by suctioning of secretions.
The primary risk during early management of the airway is movement of the neck when
there is an occult cervical spinal fracture. The airway must be controlled with the
assumption that such a fracture exists. The neck must be completely immobilized in a
neutral position. One member of the trauma team must be assigned to kneel at the head of
the stretcher to maintain inline manual stabilization of the head and avoid hyperextension
by holding the cervical spine with the hands while immobilizing the head with the
forearms (Fig. 61.1). Traction on the head is avoided, because distraction with further
injury to the spinal cord can occur if the patient has an unstable cervical spinal injury.
Once the neck of an unconscious patient has been secured, forward traction of the
mandible is performed to overcome pharyngeal collapse (Fig. 61.2). The next step is
placement of an oropharyngeal airway in the unconscious patient. If the patient is
conscious, a nasopharyngeal airway is used. Once the airway has been established and
the patient is spontaneously breathing, supplemental oxygen can be provided through
nasal prongs or a face mask.

FIGURE 61.1. Stabilization of the cervical spine during
primary survey of an injured patient.



FIGURE 61.2. Once the neck of an unconscious patient
has been secured, forward traction of the tongue and
mandible is performed.



When these simple measures are unsuccessful, more aggressive airway management is
needed. Nasotracheal intubation is the preferred technique for establishing an airway in a
conscious patient who may have a cervical spinal injury because it can be done without
excessive mobility of the neck. Nasotracheal intubation is better tolerated by an awake
patient than is orotracheal intubation and does not necessitate sedation or muscle
relaxation. Nasotracheal intubation is precluded if the patient has extensive maxillofacial
injuries.
If the nasotracheal route cannot be used, orotracheal intubation is the next step. In ideal
circumstances, a cross-table lateral cervical spine radiograph is obtained before
orotracheal intubation to evaluate for a possible cervical spinal fracture. It is nevertheless
important to remember that even a normal cross-table lateral radiograph of the cervical
spine does not definitively exclude the presence of cervical spinal fracture or instability.
When emergency airway control with orotracheal intubation is indicated, intubation
proceeds with inline stabilization whether or not radiographs have been obtained. Bag-
mask intubation can be an effective method of maintaining the airway until radiographs
are obtained. If the patient is unconscious and cervical spinal injury has been ruled out,
orotracheal intubation can be readily accomplished. A patient who is awake must be
paralyzed with succinylcholine for successful orotracheal intubation. Even normal initial
cervical spinal radiographs do not exclude the existence of an unstable cervical spinal
injury (13).
After intubation, the chest is auscultated to ensure that the tube is in the trachea and not in
the esophagus or in one of the mainstem bronchi. Correct positioning of the endotracheal
tube can be confirmed reliably by the presence of end-tidal carbon dioxide. Carbon
dioxide from the lungs can be detected rapidly by means of observation of a change in
color on a disk that can be connected rapidly to the endotracheal tube. If no carbon
dioxide is detected, the endotracheal tube is in the esophagus, and a new airway is
attempted. If the patient is in cardiac arrest, end-tidal carbon dioxide is unreliable in
confirming the positioning of an endotracheal tube. A follow-up chest radiograph to
confirm the position of the tube must be obtained expeditiously.
If an endotracheal tube cannot be inserted, as when a patient has major facial fractures or
has sustained laryngotracheal trauma, surgical airway intervention may be needed. There
are four surgical methods of obtaining an airwayneedle cricothyrotomy, conventional
cricothyrotomy, tracheotomy, and percutaneous transtracheal ventilation.
For children, needle cricothyrotomy is the best procedure. The procedure is performed by
means of placing a no. 12 or no. 14 intravenous cannula with a plastic sheath through the
cricothyroid membrane into the tracheal lumen. Once in the airway, the needle is
withdrawn and the plastic sheath is advanced. When properly positioned, the sheath is
connected with intravenous tubing to wall or bottled oxygen at 50 pounds per inch of
pressure (about 15 L oxygen per minute). Ventilation is accomplished by means of 1-
second intermittent injections of oxygen followed by 4-second exhalations. Patients can
be maintained for up to 30 minutes with this technique, after which hypercapnia becomes
a problem.
Surgical cricothyrotomy is the preferred approach for adult patients who need surgical
airway intervention (Fig. 61.3). It consists of a small vertical skin incision over the area
of the cricothyroid membrane followed by a horizontal incision through the cricothyroid
membrane itself. The blunt end of the scalpel is inserted between the cricoid and the
thyroid cartilages and rotated 90 degrees to make an opening through which an
endotracheal tube or tracheostomy tube can be inserted.

FIGURE 61.3. Cricothyrotomy.



For patients with laryngeal trauma, tracheal trauma, or tracheal disruption,
cricothyrotomy is inadvisable, and emergency tracheotomy is performed. Percutaneous
transtracheal ventilation, a technique similar to needle cricothyrotomy, is an acceptable
alternative in the treatment of these patients. Continuous monitoring of oxygenation with
pulse oximetry is extremely helpful in determining the adequacy of oxygenation of a
trauma patient and is used in the care of all critically injured patients to allow early
detection of arterial oxygen desaturation.
Breathing
Loss of respiratory drive among trauma patients is most commonly caused by severe
head trauma. Ventilation is provided with a bag mask until cervical spinal injury is ruled
out. An endotracheal tube then is inserted, and mechanical ventilation is begun. As part
of the primary survey, injuries to the chest wall and structures within the thoracic cavity
that can cause hypoventilation must be recognized and rapidly managed. These injuries
include sucking pneumothorax, massive pneumothorax, and tension pneumothorax.
Sucking pneumothorax occurs when there is a defect in the chest wall larger than the
tracheal diameter. Because of reduced resistance through this opening, inspiratory and
expiratory efforts result in movement of air through the opening in the chest wall into the
pleural space rather than through the trachea. Occlusion of the chest wall defect and chest
tube placement followed by intubation with positive pressure ventilation is the best
management of this injury.
Massive hemothorax is vented promptly. Although blood loss of 1,000 to 1,500 mL into
the thoracic cavity almost always necessitates emergency thoracotomy, initial
management is aimed at decompressing the chest cavity so that adequate ventilation can
proceed. Tube thoracotomy is performed by means of making an incision at the fourth or
fifth intercostal space in the midaxillary line (Fig. 61.4). A short subcutaneous tunnel is
developed by means of finger dissection, and the tube is passed posterosuperiorly along
an intrapleural tract toward the pleural apex. Continued hemorrhage at a rate of greater
than 200 mL per hour is an indication for thoracotomy.

FIGURE 61.4. Tube thoracostomy. An incision is made
in the fourth or fifth intercostal space in the midaxillary
line. A: A short subcutaneous intrapleural track is
developed by means of finger dissection. B: The tube is
passed posteriorly and superiorly toward the pleural apex.



Tension pneumothorax develops when a pleural, bronchial, or tracheal tear allows air to
be forced into the pleural space without a means of egress. The result is collapse of the
ipsilateral lung. As pleural pressure increases, the mediastinum and trachea shift to the
opposite side, compress the contralateral lung, and compromise oxygenation. The
mediastinal shift kinks the inferior and the superior vena cava; the kink impairs venous
return, and hypotension develops. Signs and symptoms of tension pneumothorax are
acute shortness of breath, tracheal deviation away from the injury, increased resonance to
percussion, distention of the neck veins, and decreased breath sounds over the injured
hemithorax. Tension pneumothorax is a clinical diagnosis made on these clinical
grounds. Delay to obtain and interpret a chest radiograph before decompression of the
chest may lead to the patient's death. Tension pneumothorax is managed by means of
allowing air to escape through needle thoracocentesis with a large-bore, 12-gauge
intravenous cannula inserted into the second intercostal space in the midclavicular line
(Fig. 61.5), followed by definitive treatment with insertion of a chest tube. Pneumothorax
also can cause hypotension owing to its effect on myocardial performance. Any patient
who remains in shock after chest trauma needs empirical ventilation of the chest.

FIGURE 61.5. Needle thoracentesis for management of
pneumothorax. The needle is inserted into the second
intercostal space in the clavicular line.



Circulation and Shock
Once the airway and breathing have been reestablished, the next step is to assess the
adequacy of the circulatory system. Shock is the clinical manifestation of the inability of
the heart to maintain adequate circulation to vital organs. This low-flow state can be
caused by dysfunction of the heart, loss of blood volume, loss of vascular resistance, and
an increase in venous capacity (10). The cellular response to shock is a shift from aerobic
to anaerobic metabolism in nonvital organ systems. The result is lactic acidosis. If
hypoperfusion persists, oxygen delivery to vital organs becomes inadequate, and acidosis
deepens. Unless oxygenation and perfusion are restored, organ failure progresses, and the
patient dies.
The clinical presentation of shock depends on the severity. A patient with mild shock
may be anxious and restless; if shock is severe, the patient looks apathetic or exhausted.
The skin is cool and sallow with evidence of decreased capillary filling, particularly in
the nail beds. Thirst, nausea, and vomiting are common. Blood pressure is low, and the
pulse is fast and weak. Poor filling of peripheral veins makes it difficult to place
intravenous catheters. There are four categories of shockhypovolemic shock,
neurogenic shock, cardiogenic shock, and septic shock. The first three are associated with
the acute phase of trauma.
Hypovolemic Shock
Hypovolemia is the most common cause of shock after trauma.
Hemorrhage is assumed to be the cause unless proved otherwise.
Attempts have been made to classify the severity of hemorrhagic shock as follows to give
better guidelines for resuscitation:
Class I hemorrhage is the loss of about 15% of blood volume. The primary manifestation
is mild anxiety.
Class II hemorrhage is the loss of 15% to 30% of blood volume. The result is tachycardia
and tachypnea, anxiety, decreased capillary refill, and decreased urine output. Supine
blood pressure remains normal.
Class III hemorrhage is the loss of 30% to 40% of blood volume. Patients often are
extremely anxious or combative and have marked tachycardia and tachypnea, prolonged
capillary refill time, and a marked decrease in urine output. Only at this stage of severe
hypovolemia does supine hypotension occur.
Class IV hemorrhage is the loss of more than 40% of blood volume. The result is marked
hypotension and tachycardia. Urine output is almost completely shut off, and mental
status can range from anxiety to coma. Losses of this magnitude often are lethal.
The management of hypovolemia is rapid volume replacement. The patients most
needing acute fluid resuscitation are those in whom venous access usually is the most
difficult. For most patients, 14-gauge intravenous catheters can be inserted into the
antecubital veins with little difficulty. If the systolic blood pressure is so low that
percutaneous access in the antecubital spaces is precluded, cutdown of the greater
saphenous vein can be performed. Percutaneous femoral vein or subclavian
catheterization is another alternative, but the surgeon must be familiar with the anatomic
features of the area (1,2,3,4,5,6 and 7,10,12).
Crystalloids, such as lactated Ringer solution or normal saline solution, are the preferred
fluids for resuscitation. In adults, blood volume is about 7% of total body weight (about 5
L for a normal-sized man). In children, blood volume is 8% or 9% of total body weight;
in infants, 10%. The requirements for crystalloid resuscitation can be based on the results
of clinical assessment of the percentage of blood loss and the knowledge of the
approximate blood volume of the patient. Circulating volume can be restored by means of
infusing 3 mL crystalloid solution for each milliliter of estimated blood loss. This ratio
can be much greater in massive hemorrhage. The crystalloid solution is infused as rapidly
as possible until blood pressure and heart rate return to acceptable levels. Further fluid
replacement can be monitored according to the adequacy of the urine output (1,2,3,4,5,6
and 7,10,12).
There is a degree of blood loss beyond which crystalloid replacement is inadequate, and
blood replacement is necessary. As a rule, trauma patients who arrive in the emergency
department with supine hypotension likely need transfusion. Blood is added to
resuscitation when the crystalloid infusion exceeds 50 mL per kilogram. Cross-matched,
type-specific blood rarely is available to acutely injured patients, but un-cross-matched
type-specific whole blood can be obtained rapidly in most hospitals and rarely causes
serious complications. If type-specific blood is unavailable, type O-negative (universal
donor) blood can be given safely to a trauma patient in need of emergency blood
transfusion. The risk of transfusion reactions with O-negative blood in this situation is
minimal.
Substantial clotting problems can occur with massive crystalloid and blood replacement
therapy for hemorrhagic shock. Although blood components are not used in early
resuscitation, dilutional coagulopathy can develop after substantial transfusion. This
dilutional coagulopathy is managed with fresh-frozen plasma and platelet transfusion,
depending on the degree of ongoing bleeding. Platelets and fresh-frozen plasma are
administered according to the degree of coagulopathy, not the specific number of units of
blood administered. As a rule, use of fresh-frozen plasma can be considered after the
tenth unit of banked blood and then after every fourth unit. Use of platelets can be
considered after the fifteenth unit of blood, and then after every fifth unit. Coagulation
profiles can be monitored.
Adjunctive steps can be helpful in the care of patients sustaining hemorrhagic trauma. In
cases of external hemorrhage, the bleeding often can be controlled with minimal pressure.
Tourniquets usually are not helpful, because compression usually controls the blood loss.
Blind clamping must be avoided to prevent injury to adjacent nerves. The scalp may be
the source of profuse bleeding, and rapid temporary suturing may be needed.
Military antishock trousers (MAST), which are inflatable pants, can be placed around the
patient's legs and pelvis to decrease circulation to the extremities and thereby improve
central circulation. They are not meant to replace adequate fluid therapy but can be useful
in the prehospital phase of the trauma delivery system. Caution must be exercised in the
use of MAST because inflation of the abdominal compartment can impair respiration,
and overinflation of the leg compartments for long periods can cause compartment
syndrome.
Neurogenic Shock
The purpose of fluid restoration is to reestablish adequate perfusion to vital organs.
Measurements such as blood pressure, heart rate, urinary output, and level of
consciousness help measure the success of fluid resuscitation. When these signs do not
change in response to adequate resuscitation, other causes must be suspected. One such
cause can be neurogenic shock, which is caused by brainstem dysfunction or spinal cord
injury that denervates the sympathetic nervous system. The result is vasodilatation and
decreased peripheral vascular resistance and consequent loss of blood pressure. The
characteristics of neurogenic shock are the absence of tachycardia, warm extremities, and
lack of anxiety in the presence of hypotension. No patient should be presumed to have
neurogenic shock, despite evidence of neurologic injury, until all other causes of shock
have been systematically evaluated and eliminated. Once this has been done,
management of neurogenic shock is fluid resuscitation to replete intravascular volume,
vasopressors to restore lost vascular tone, and appropriate neurosurgical intervention
(10).
Cardiogenic Shock
Cardiogenic shock is loss of circulatory perfusion because the myocardium cannot
produce sufficient flow to maintain tissue oxygenation. Among trauma patients,
cardiogenic shock is generally associated with three injuries: tension pneumothorax,
cardiac tamponade, and myocardial contusion. Cardiogenic shock is suspected when
hypotension persists despite appropriate resuscitation. The most common features of
cardiogenic shock are distended jugular veins and elevated central venous pressure in the
presence of hypotension. These signs may not occur until the patient has undergone
adequate fluid replacement. Cardiogenic shock may coexist with hypovolemic shock.
A common feature of tension pneumothorax is impaired myocardial function due to
decreased venous return. Increasing intrathoracic pressure distends the jugular veins and
causes hypotension. In an emergency, tension pneumothorax can be confused with
cardiac tamponade because both conditions are associated with hypotension and
distention of the neck veins. In some instances, it is impossible to differentiate these two
conditions, and empiric thoracocentesis is necessary on the side most likely to be
affected. If there is a rush of air with restoration of hemodynamic status, the diagnosis of
tension pneumothorax is confirmed. If not, the procedure is repeated on the opposite side
of the chest. If the patient's condition does not improve, cardiac tamponade is considered,
and the patient is empirically treated.
Cardiac tamponade in a trauma patient is caused by accumulation of blood between the
myocardium and its pericardial covering. When this is acute because the pericardium is
nondistensible, small volumes of blood can accumulate if the patient has marked
myocardial impairment. The pathophysiologic changes leading to cardiogenic shock are
caused by a decrease in ventricular filling during diastole and impairment of myocardial
contractility due to ischemia from impairment of the coronary circulation. The classic
signs of cardiac tamponade are hypotension, jugular venous distention, and distant heart
sounds. The jugular veins may not become distended if the patient has hypovolemia; thus
diagnosis often is made as the result of suspicion based on an injury such as a penetrating
chest wound.
Emergency department treatment of a patient with cardiac tamponade is
pericardiocentesis (Fig. 61.6). The procedure is performed by means of insertion of a 14-
or a 16-gauge catheter in the left subxyphoid position with the needle aimed toward the
posterior portion of the left shoulder. Aspiration of as little as 10 to 20 mL of blood can
bring about dramatic improvement in myocardial function; however, the high frequency
of false-negative and false-positive results under extreme circumstances may prompt a
left anterior thoracotomy with direct pericardial decompression.

FIGURE 61.6. Pericardiocentesis for acute cardiac
tamponade performed through the left subxyphoid
approach.



Emergency thoracotomy is an option when a trauma patient does not respond to
resuscitation and is in cardiac arrest. Other considerations for emergency thoracotomy
include initiation of direct cardiac massage and control of massive hemothorax due to
cardiac puncture or tears in the thoracic aorta.
Myocardial contusion, another cause of cardiogenic shock after trauma, is caused by
blunt injury, typically when the chest hits a steering wheel. Physical signs include
ecchymotic discoloration of the anterior chest wall and flail chest. Severe myocardial
contusion is unusual, whereas blunt chest trauma is common. The existence of marked
myocardial contusion can be confirmed with transthoracic or transesophageal
electrocardiography. Wall motion, valvular dysfunction, and the presence of pericardial
fluid or tamponade can be seen with echocardiography. Management is aimed at
preventing fluid overload while maintaining cardiac output and medically suppressing
ventricular arrhythmia. With the increasing frequency of trauma among elderly patients,
the possibility of an acute myocardial infarction, arrhythmia, or congestive heart failure
precipitating an accident must be strongly considered (10).
Secondary Survey
The secondary survey consists of a detailed physical examination with the patient fully
exposed. It is undertaken once the lifesaving priorities of the primary survey have been
addressed. The breadth and speed of this examination depend in large measure on the
patient's injuries and the need for definitive surgical intervention. Valuable information
regarding the patient's history must be collected, including the mechanism of injury,
preexisting medical problems, current medications, known drug allergies, and when the
patient last ate. Routine objective studies also can be performed at this time, including a
complete blood cell count, chest radiography, and urinalysis. If drug overdose or alcohol
consumption is suspected, appropriate toxicologic studies can be performed. Hypotension
warrants blood typing and cross-matching.
Head and Spine Injuries
Alterations in mentation are the most frequent signs of injury to the CNS. Although it can
be caused by intoxication, altered consciousness of a trauma patient is presumed to be
caused by injury until proved otherwise. Cervical spinal and spinal cord injuries are
common among patients with multiple injuries, and the greatest concern is to avoid
further injury to vital neurologic structures. Rigid immobilization of the cervical spine is
imperative until a complete set of spinal radiographs, including cervical, thoracic, and
lumbar spine radiographs, has been obtained. The entire spine is palpated for tenderness
and altered contour. For patients with definitive cervical spinal injuries, use of a rigid
collar reinforced with sandbags on either side and wide tape across the forehead is
mandatory (Fig. 61.7).

FIGURE 61.7. For patients with definitive cervical
spinal injuries, use of a rigid collar reinforced with
sandbags on either side and wide tape across the forehead
is mandatory.



Alterations in mental status can be caused by direct injury to the cortex and brainstem
and by increased intracranial pressure (ICP) and decreased cerebral perfusion. Whereas
the first two conditions necessitate formal neurosurgical intervention, the changes in
pressure and perfusion can be managed in the emergency department. The tool used to
assess mental status is an abbreviated neurologic examination to define the Glasgow
Coma Scale score (Table 61.1). This graded evaluation is performed to assess the
functions of eye opening, verbal response, and motor response. A Glasgow score less
than 8 indicates serious head injury, although the score can be artificially low if an
endotracheal tube is in place. Further neurologic assessment includes evaluation of
pupillary reflexes, deep tendon reflexes, and rectal sphincter tone. A serious head injury
can have nonneurologic signs such as hypoventilation and hypertension.

TABLE 61.1. GLASGOW COMA SCALE



Emergency department treatment of a patient with a head injury is aimed at minimizing
cerebral edema and reducing ICP. These goals are met by means of controlling the
airway to maintain acceptable oxygenation. The old recommendation for hyperventilation
to reduce serum carbon dioxide levels to less than 30 mm Hg has been abandoned.
Excessive hyperventilation causes cerebral vasoconstriction and a marked reduction in
cerebral blood flow. Ventilation is adjusted to maintain a carbon dioxide level of about
35 mm Hg. Patients with suspected cerebral trauma and a Glasgow Coma Scale score less
than 8 need continuous monitoring of ICP. Intracranial pressure is maintained at less than
20 mm Hg. Elevations in ICP are managed by means of administration of the osmotic
diuretic, mannitol, to reduce the amount of intracellular water in the brain.
Ventriculostomy can be used to monitor ICP and can be therapeutic in that it allows
removal of cerebrospinal fluid to control ICP. Maintenance of cerebral blood flow,
measured as a cerebral perfusion pressure (mean arterial pressure minus ICP) of 70 mm
Hg with the use of fluids and vasopressors, is gaining increasing acceptance. There is no
role for the administration of steroids for the control of cerebral trauma. Any patient who
has changes in mental status after injury needs cranial computed tomography (CT) as part
of the secondary survey (14).
The management of spinal cord injury with distal deficits has changed over the last
several years. Emphasis remains on maintaining spinal immobilization to prevent
additional spinal cord injury. Recent research (15) has found that administration of
steroids can play a role in minimizing neurologic deficits for patients with spinal cord
injuries. Administration of methylprednisolone as a bolus of 30 mg/kg followed by a drip
at 5.4 mg/kg each hour for 23 hours led to small improvement in neurologic function
among these patients when administered within 8 hours of the injury.
Once the neurologic system has been evaluated, the secondary survey continues with
assessment of the rest of the head. The scalp can be a source of considerable blood loss,
and immediate suturing may be needed. Basilar skull fractures can manifest as mobility
of the facial bones, hemotympanum, cerebral spinal fluid otorrhea and rhinorrhea, and
periorbital and mastoid ecchymosis.
Neck Injuries
All injuries to the neck are potentially life threatening because numerous vital structures
traverse this area. Neck injuries are classified as blunt or penetrating. Blunt trauma to the
neck can cause cervical spinal injury, pharyngeal and tracheal injuries, and carotid artery
injury. Penetrating neck wounds are classified according to location. Zone I injuries are
below the level of the clavicles, zone II injuries are between the clavicles and the angle of
the jaw, and zone III injuries are above the angle of the jaw (Fig. 61.8). Posterior injuries
can damage the cervical spine. Anterior and lateral wounds can injure the great vessels of
the neck, the larynx, the trachea, and the esophagus as well as important nerves such as
the vagus, phrenic, hypoglossal, spinal accessory, and branchial plexus. High penetrating
injuries (zone III) threaten the great vessels and cranial nerves at the base of the skull;
penetrating injuries at the base of the neck (zone I) threaten the great vessels exiting the
thorax.

FIGURE 61.8. Penetrating neck wounds are classified
according to location. Zone I injures are below the level
of the clavicles. Zone II injures are between the clavicles
and the angle of the jaw. Zone III injures are above the
angle of the jaw.



Clinical examination of an injured neck involves careful assessment of the airway,
including evaluation for hoarseness, stridor, dyspnea, and hemoptysis. Subcutaneous
emphysema, crepitus, and distorted laryngeal landmarks indicate laryngotracheal injury.
Dysphagia and chest pain are characteristic of esophageal injuries. Fiberoptic
laryngoscopy is an excellent tool for examining the hypopharynx and larynx after neck
injuries. It is rapid and easy to use and provides an excellent way to evaluate the patency
of the airway and the function of the larynx. Fiberoptic laryngoscopy also can aid in the
diagnosis of laryngeal fractures and vagal injuries. Computed tomography of the neck
also can help to delineate laryngeal fractures.
When laryngeal or tracheal injury is apparent and airway compromise is imminent,
tracheotomy is performed. Cricothyrotomy is not used under such circumstances because
of the risk of further injury to the larynx and upper trachea. Although it may be necessary
to perform tracheotomy in the emergency department, this procedure is best done in the
operating room, where proper instrumentation, optimal lighting, and appropriate
personnel are available, especially when the patient has sustained blunt laryngotracheal
disruption. This injury usually is caused by severe compression of the laryngotracheal
complex between the steering wheel and the vertebral column or from clothesline
injury, such as catching the neck on a string of fence while riding a snowmobile or a
motorcycle. Under these circumstances, active airway management can be fraught with
danger. Intubation may not be feasible, and tracheotomy can cause retraction of the distal
trachea into the mediastinum.
Patents with penetrating neck injuries are at risk of airway obstruction, hemorrhage, and
injury to the cervical spine. Important clinical signs include stridor, hoarseness,
subcutaneous emphysema, expanding hematoma, external hemorrhage, hemoptysis,
dysphagia, cranial nerve dysfunction, and branchial plexus injury. Active airway
intervention is important when there is evidence of airway distress. It is best
accomplished with nasotracheal or orotracheal intubation. Bleeding in the oropharyngeal
area may preclude intubation and necessitate emergency surgical airway intervention,
which can cause great difficulty if there is bleeding in the deeper layers of the neck.
External hemorrhage is controlled with compression, and no effort is made to gain
hemostasis by means of blind clamping.
There has been much controversy with regard to routine exploration of penetrating neck
injuries, not only as definitive treatment but also as a diagnostic technique. Some authors
advocate routine exploration of all injuries penetrating the platysma. Others advocate
selective exploration and observation based on preoperative arteriographic findings and
on the presence or absence of symptoms that suggest vascular, airway, and neurologic
injury.
Most patients in stable condition with penetrating injuries to the base of the neck (zone I)
are best examined by means of arteriography, laryngoscopy, and esophagoscopy or a
barium swallow radiographic study. Patients in stable condition with penetrating injuries
above the angle of the mandible (zone III) are best examined with arteriography to
exclude carotid or vertebral artery injury. Patients with injuries between the angle of the
mandible and the base of the neck (zone II) can be examined by means of routine
exploration or combinations of arteriography, laryngoscopy, and esophageal evaluation if
the injury has penetrated the platysma. Patients in unstable condition with active
hemorrhage need surgical exploration.
When a patient has marked neurologic deficits after blunt neck trauma and the findings of
CT of the head are normal, the possibility of blunt carotid injury with carotid occlusion or
dissection is considered and excluded, but with arteriography. Management of these
injuries involves anticoagulation with heparin or reconstruction, depending on the nature
of the injury.
Thoracic Injuries
Thoracic injuries are classified as blunt or penetrating. Most blunt injuries are caused by
motor vehicle accidents. Penetrating injuries typically are from violence with knives or
guns. The principal forms of life-threatening blunt chest trauma are flail chest, pulmonary
contusion, tracheobronchial disruption, and torn thoracic aorta.
Flail chest occurs when part of the chest wall becomes isolated owing to multiple
fractures of the ribs or sternum (Fig. 61.9). The severity is determined by the size of the
flail segment, which moves paradoxically with inspiration and thus reduces ventilatory
efficiency. Ventilation is further compromised by the size of the underlying pulmonary
contusion that invariably accompanies a severe flail chest. If ventilation becomes
inadequate, hypoxia and hypercapnia occur and the patient needs intubation and
ventilatory assistance.

FIGURE 61.9. Flail chest.



Pulmonary contusion is a common finding in blunt chest trauma. It often is associated
with flail chest and hemopneumothorax and is common in multisystem trauma.
Pulmonary contusion causes alveolar edema and impairs gas exchange. The primary sign
of pulmonary contusion is hypoxia. Initial management is adequate oxygenation and
avoidance of fluid overload, which can promote pulmonary edema. If a patient has
hypovolemia and pulmonary contusion, aggressive fluid resuscitation is indicated,
regardless of the presence of the lung injury. Intubation and mechanical ventilation often
are needed to support respiration.
Most intrathoracic blunt tracheobronchial injuries are caused by compression of the
trachea and bronchi between the sternum and the vertebral column in motor vehicle
accidents. The areas most commonly involved are the proximal mainstem bronchi and the
distal trachea. Common features of this injury include pneumothorax, subcutaneous
emphysema, and hemoptysis. Initial therapy often entails venting the pneumothorax.
Bronchoscopy is indicated for diagnosis.
Traumatic rupture of the thoracic aorta is the most common cause of immediate death
after motor vehicle accidents. In 90% of cases, the aortic injury occurs beyond the origin
of the left subclavian artery at the level of the ligamentum arteriosum, where the
descending aorta is relatively fixed. Motion between the more mobile aortic arch and
fixed descending aorta can cause aortic injury when rapid deceleration is the mechanism
of injury. In about 10% to 20% of cases, rupture of the thoracic aorta does not cause
immediate death because intrathoracic hemorrhage is contained by the aortic adventitia,
and the patients can be saved if the injury is rapidly recognized. Although arteriography
is the only definitive study for the diagnosis of this injury, the first indication of an aortic
tear usually is evidence of superior mediastinal widening on routine chest radiographs.
Clinical features, such as retrosternal or interscapular pain from mediastinal blood
dissection and hypertension from sympathetic stimulation of the nerves around the aorta,
can provide clues to the presence of rupture of the aorta. Early recognition and definitive
surgical repair are crucial because the rupture becomes complete in a high percentage of
patients within the first 24 to 48 hours after injury. The decision to perform thoracic
arteriography to exclude aortic disruption is made early in the resuscitation and is based
on findings of mediastinal widening on the initial supine chest radiograph obtained in the
emergency department.
The injuries associated with penetrating thoracic traumahemopneumothorax, tension
pneumothorax, and cardiac tamponadeare discussed earlier. After immediate
management, a decision must be made regarding surgical thoracotomy when there is
persistent bleeding from a chest wound. Considerations include the volume of the initial
chest tube drainage, the rate of ongoing hemorrhage once the lung has been reexpanded,
and the patient's hemodynamic status.
Abdominal Injuries
Abdominal injuries are life threatening because of the capacity of the peritoneal cavity
for occult blood loss and the risk of fecal contamination. Unrecognized abdominal injury
is a common cause of death after trauma, and prompt recognition is of primary
importance in its prevention. Diagnosis can be delayed by the silent nature of the injury,
other life-threatening problems, or an altered state of consciousness.
Examination of the abdomen begins at the level of the nipples and extends to the pubic
symphysis. The examination includes inspection, auscultation, percussion, and palpation.
Rectal examination is mandatory for assessment of sphincter tone, pelvic crepitus,
position of the prostate, and hemorrhage. Although the absence or presence of bowel
sounds may not correlate well with the presence of injury, other signs, such as abdominal
tenderness, are highly suggestive of peritoneal inflammation and can indicate the need for
laparotomy.
Abdominal injuries are classified as blunt or penetrating. Blunt abdominal injuries
usually are associated with injury to solid organs, such as the liver, spleen, pancreas, and
kidneys. The most common finding among patients with blunt abdominal trauma and
solid organ injuries is hemoperitoneum with shock. Peritoneal lavage is the preferred
triage tool in the initial treatment of patients in hemodynamically unstable condition or of
patients who need emergency surgery for other reasons. Specific indications include
equivocal physical findings in a patient with a suspicious injury or unexplained
hypovolemic shock when the chest radiographic findings are normal. Initial peritoneal
aspiration of more than 10 mL of blood is an indication for laparotomy.
Lavage is performed by means of instilling 15 mg/kg normal saline solution into the
peritoneal cavity and letting the fluid drain out by means of gravity. When the total
erythrocyte count in the lavage effluent exceeds 100,000 per milliliter, most patients have
abnormal findings at laparotomy. Abdominal CT is an excellent diagnostic study to
exclude intraperitoneal or retroperitoneal injury if the patient is in hemodynamically
stable condition. As experience with abdominal CT has increased, it has become clear
that many patients with minor liver and spleen injuries with hemoperitoneum stop
bleeding spontaneously and never need abdominal exploration. Abdominal
ultrasonography in the emergency department has been used to exclude hemoperitoneum
among trauma patients. Ultrasonography can depict the presence of intraperitoneal blood
with a high degree of specificity. The absence of fluid in the abdomen also reliably
excludes hemoperitoneum and strongly suggests that no intraabdominal injury is present.
The advantage of ultrasonography is that the equipment is portable and that the study can
be performed in about 5 minutes in the trauma room while resuscitation continues (16).
Patients with penetrating abdominal trauma and overt signs of peritonitis or hypovolemia
need surgical exploration; however, therapy is less clear-cut when the patient's condition
is hemodynamically stable or when signs of peritonitis have yet to evolve. The common
mechanisms of penetrating trauma are gunshot wounds and stab wounds. With gunshot
wounds, laparotomy is indicated when the missile penetrates the peritoneum. Plain
abdominal radiographs are obtained to outline the missile trajectory. Broad-spectrum
antibiotics are administered in anticipation of definitive surgical therapy.
Stab wounds of the abdomen can be managed selectively because the likelihood of
visceral injury, even with peritoneal violation, is inconsistent. The first diagnostic steps
are to ascertain the depth of the injury and to assess the integrity of the peritoneum. These
steps are best done by means of exploring the wound in the emergency department with
the patient under local anesthesia. Peritoneal lavage follows local exploration if there is in
an indication that the anterior muscular fascia has been penetrated. Criteria for a positive
peritoneal lavage result differ in blunt injuries from stab wounds. Although 100,000
erythrocytes per milliliter is the accepted positive result for blunt injuries, an erythrocyte
count of 5,000 to 10,000 per milliliter is accepted as a positive result in a stab wound and
indicates that laparotomy is needed. Patients with positive peritoneal lavage results need
exploratory laparotomy. Those with negative peritoneal lavage results can be admitted for
observation.
Extremity Injuries
During the secondary survey, the arms and legs are examined carefully to assess
perfusion, neurologic function, deformity, and range of motion. Serious injuries include
fractures, dislocations, amputations, and compartment syndromes. Life-threatening
injuries involve massive blood loss due to pelvic fractures, traumatic amputations, and
open femoral fractures. Pelvic fractures associated with hypovolemia are stabilized with
application of MAST. An expanding hematoma or pulsatile, bright red bleeding indicates
acute arterial injury and is controlled with manual pressure.
Before it is assumed that bleeding is coming from a pelvic fracture when the patient's
condition is unstable, it is necessary to exclude ongoing intrathoracic or intra-abdominal
hemorrhage. Supraumbilical diagnostic peritoneal lavage may be indicated to exclude an
intra-abdominal source of hemorrhage in these patients. In the care of patients with
persistent pelvic hemorrhage, angiography is indicated for diagnosis and definitive
management by means of embolization of the bleeding vessels by vascular radiologists.
A direct surgical approach to the bleeding pelvis rarely is indicated.
Rectal and vaginal examinations are an important part of the management of pelvic
fractures. Patients with severe pelvic fractures may have associated injuries to the vagina,
rectum, and urethra. A high-riding prostate or a positive result of a heme test of stool can
alert the clinician to this possibility. Bladder rupture also is considered if a patient has a
pelvic fracture and hematuria. An abnormal result of a prostate examination or blood at
the urethral meatus indicates urethral injury and is a contraindication to insertion of a
Foley catheter. Under this circumstance, retrograde urethrography is performed before a
Foley catheter is placed.
Vascular injuries can be associated with penetrating wounds, fractures, and joint
dislocation. Signs are typically those of ischemia, and the patient has pain, pallor,
paralysis, paresthesia, and pulselessness. Recognition is important to preserve the
extremity, and the diagnosis is confirmed with arteriography. Dislocation of the knee
often is associated with popliteal artery injury and distal ischemia. Angiography of the
popliteal artery usually is recommended to exclude injury if a patient has a knee
dislocation.
Crush injuries to the lower leg and forearm can cause compartment syndrome due to
hemorrhage and edema within recognized fascial planes. The patient typically has a
painful, pale extremity with decreased sensation and pulse. The earliest sign of
compartment syndrome is the patient's report of paresthesia or sensory deficit in the limb.
Loss of peripheral pulses is a relatively late finding and often implies irreversible damage
to the limb. Compartment syndrome occurs most often with closed fractures of the tibia
and fibula. Emergency fasciotomy is the appropriate therapy.
Traumatic amputation necessitates microsurgical reimplantation when possible. Bleeding
from the proximal limb is controlled with manual pressure. The amputated parts must be
kept in a moistened sterile towel and placed in crushed ice until definitive therapy can be
provided (4,5,6 and 7).
Inhalation Injuries
Thermal injuries must be managed in an orderly way, similar to that of all serious
traumatic injuries. Most inhalation injuries are caused by fires in closed spaces, but the
possibility of blunt injuries to the throat or abdomen, as in blast injures or car accidents
with fires, must be considered. An otolaryngologist may be asked to facilitate airway
management for patients with inhalation injuries.
Although all types of trauma are suspect, specific types, such as explosive burns and
burns sustained in a confined building, are associated with inhalation injury. Physical
signs of inhalation include a decreased level of consciousness, singed nasal hairs, carbon
deposits in the oral cavity, carbonaceous sputum, and the finding of inflammatory
changes in the supraglottic larynx at fiberoptic laryngoscopy.
The subglottic airway often is protected from burns unless the patient is exposed to
superheated gas or steam. The glottic and supraglottic airway can sustain marked edema
from routine thermal trauma. The result is immediate or delayed airway obstruction.
Patients with clear signs of supraglottic inhalation injuries need early endotracheal
intubation with mechanical ventilation. Carbon monoxide levels in the blood should be
measured. Hyperbaric oxygen therapy is considered when a patient has marked carbon
monoxide poisoning (7).
Definitive Management
Once the primary and secondary surveys have been completed, the patient has been
adequately resuscitated, and the patient's condition is judged to be stable, a plan for
definitive care is formulated. This plan begins with a ranking of the injuries in the order
in which they are to be managed. If at any point the vital signs become unstable, the
primary and secondary surveys are repeated. If the instability is from an injury that
warrants definitive surgical intervention, the patient is transferred to the operating room.
Patients who do not need further surgical intervention are transferred to the intensive care
unit or to a surgical floor for further observation. Transfer errors include inadequate
management of the airway, poorly secured intravenous lines and drainage tubes, and
inadequate patient monitoring. It is a tragedy to resuscitate a patient in the emergency
department successfully only to lose the patient on transfer to the operating room.
ROLE OF THE OTOLARYNGOLOGIST
Since the early 1970s, the responsibility of otolaryngologists as members of the trauma
team has continued to expand. In most institutions, otolaryngologists are viewed as
experts in managing the airway and are expected to perform difficult intubations and
provide emergency surgical airways. They are also being recognized for expertise in the
management of maxillofacial trauma and penetrating injuries to the neck.
Otolaryngologists often are called on to assist in the immediate care of trauma victims in
the emergency department.
As valued members of the trauma team, otolaryngologists must continue to refine
management skills for injuries associated with the specialty but also need to be
knowledgeable about the general care of trauma patients. Otolaryngologists need to
understand the concepts of the primary and secondary survey and be capable of
stabilizing the neck, securing the airway, placing chest tubes, and starting intravenous
lines. They also should be able to perform the complete examinations needed in the
secondary survey and know how to interpret the diagnostic procedures that must be
performed as part of the survey. To be fully integrated and recognized as responsible
members of the trauma team, otolaryngologists involved in the care of trauma patients
should be certified by the American College of Surgeons advanced trauma life support
course.

HIGHLIGHTS
The most fundamental neuroendocrine reaction to trauma is the
release of catecholamines, which cause vasoconstriction,
increase cardiac rate, increase myocardial contractility and
conductivity, and stimulate gluconeogenesis.
The postinjury period is characterized by catabolism with
negative nitrogen balance, hyperglycemia, and heat production,
all of which reflect the reparative processes.
The most important factor in the successful care of trauma
patients is the initial evaluation and resuscitation performed
partly in the field and in the emergency department. Primary
and secondary surveys allow physicians to manage complex
multisystem problems. This treatment algorithm has four
stepsprimary survey, resuscitation, secondary survey, and
definitive care.
The foremost emergency measure after trauma is establishment
of an airway. The primary risk during early airway management
is movement of the neck when there is an occult cervical spinal
fracture. When the airway is being controlled, it must be
assumed that such a fracture exists.
Correct positioning of the endotracheal tube can be confirmed
reliably by the presence of end-tidal carbon dioxide. If no
carbon dioxide is detected, the endotracheal tube is in the
esophagus, and a new attempt at intubation is made
immediately.
Continuous monitoring of oxygenation with pulse oximetry is
extremely helpful in determining the adequacy of oxygenation
of a trauma patient and is used in the care of all critically
injured patients.
Techniques of surgical airway management include needle
cricothyrotomy, standard cricothyrotomy, tracheotomy, and
percutaneous tracheal ventilation. Needle cricothyrotomy is the
best procedure for children; surgical cricothyrotomy is
preferred for adults.
Loss of respiratory drive among trauma patients most
commonly is caused by severe head trauma; however, injuries
to the chest wall and thoracic structures can cause
hypoventilation, which must be recognized and rapidly treated.
Shock is the clinical manifestation of the inability of the heart
to maintain adequate circulation to vital organs. The patient
dies unless oxygenation and perfusion are restored. The most
common cause of shock after trauma and hemorrhage is
hypovolemia. Treatment is rapid volume replacement with
crystalloids, such as lactated Ringer solution or normal saline
solution through two 14-gauge catheters in the antecubital
fossa.
Cardiogenic shock is loss of circulatory perfusion that occurs
when the myocardium does not generate sufficient blood flow
for tissue oxygenation. Among trauma patients, cardiogenic
shock usually is precipitated by tension pneumothorax, cardiac
tamponade, or myocardial contusion. The presence of
myocardial contusion is best confirmed with echocardiography.
Among elderly trauma patients, the possibility that acute
myocardial infarction or arrhythmia has precipitated an accident
must be considered.
In the care of patients with head trauma, ventilation is adjusted
to maintain a carbon dioxide level of about 35 mm Hg. Patients
with cerebral edema or coma need continuous monitoring of
ICP. Intracranial pressure must be maintained at less than 20
mm Hg. Elevation in ICP is managed with mannitol.
Maintenance of cerebral blood flow as measured by cerebral
perfusion pressure is best accomplished with the use of fluids
and vasopressors.
In the care of patients with spinal cord injury, administration of
methylprednisolone as a bolus of 30 mg/kg followed by a drip
at 5.4 mg/kg each hour for 23 hours has been shown to lead to
small but important improvements in neurologic function if
administered within 8 hours of injury.
The decision to perform thoracic arteriography to exclude aortic
disruption must be made early in resuscitation. The decision is
based on findings of mediastinal widening on the initial supine
chest radiograph obtained in the emergency department.
Unrecognized abdominal injury is a common cause of death
after trauma. Peritoneal lavage is the preferred step in the initial
phase of assessment and management. A total erythrocyte count
of 100,000 per milliliter correlates with positive findings at
laparotomy after blunt abdominal trauma. For patients with
penetrating abdominal trauma, a total erythrocyte count of
5,000 to 10,000 per milliliter correlates with positive findings at
laparotomy.
Abdominal CT is an excellent diagnostic study to exclude
intraperineal and retroperineal injury if the patient is in
hemodynamically stable condition.
Abdominal ultrasonography can be used in the emergency
department to exclude hemoperitoneum in trauma patients and
can be performed in the trauma room of the emergency
department during resuscitation.
The extremity injury that poses the greatest risk to life is a
pelvic fracture that causes resulting in massive blood loss. The
best initial management is application of MAST followed by
angiography.
The earliest sign of compartment syndrome is the patient's
report of paresthesia or sensory deficit in the limb. Loss of
peripheral pulse is a relatively late finding and often implies
irreversible damage to the limb. Compartment syndrome occurs
most often with closed fractures of the tibia and fibula.
Amputated body parts must be kept in a moist and sterile towel
and placed in crushed ice until definitive reimplantation can be
provided.
The physical signs of inhalation injury include a decreased level
of consciousness, burned nasal hairs, carbon deposits in the oral
cavity, and inflammation of the supraglottic structures. Signs of
this type of injury are indications for early endotracheal
intubation and mechanical ventilation.
Definitive management follows the primary and secondary
surveys and begins with ranking of the injuries in the order in
which they are to be managed. If at any point the vital signs
become unstable once again, the primary and secondary surveys
are repeated. Transfer out of the emergency department for
definitive management can be a period of risk. Transfer errors
include inadequate management of the airway, poorly secured
intravenous lines and drainage tubes, and inadequate patient
monitoring.
To be fully integrated and recognized as responsible members
of the trauma team, otolaryngologists involved in the care of
trauma patients should be certified by the American College of
Surgeons advanced trauma life support course.
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11. Hill AG, Hill GL. Metabolic response to severe injury. Br J Surg 1998;85:884890.
12. Boldt J, Muller M, Mentges D, et al. Volume therapy in the critically ill: is there a difference?
Intensive Care Med 1998;24:2836.
13. Hastings RH, Marks JD. Airway management in patients with potential cervical spine injuries.
Anesth Analg 1991;73:471482.
14. Bullock R, et al. Guidelines for the management of severe head injury. Brain Trauma Foundation,
1995.
15. Bracken MB, Shepard MJ, Collins WR, et al. A randomized controlled trial of methylprednisolone
or naloxone in the treatment of acute spinal cord injury: results of the Second National Acute
Spinal Cord Injury Study. N Engl J Med 1990;322:14051411.
16. Shackford SR. Focused ultrasound examinations by surgeons: the time is now. J Trauma
1993;35:181182.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

62 AURICULAR TRAUMA
Head & Neck SurgeryOtolaryngology
62




AURICULAR TRAUMA
KAREN H. CALHOUN

K.H. Calhoun: Department of Otolaryngology, University of Texas Medical Branch at Galveston,
Galveston, Texas.


Hematoma
Lacerations and Abrasions
Total and Subtotal Avulsion
General Concepts
Total Avulsion
Partial Avulsion
Frostbite
Burns
Keloids
Chapter References
The main function of the auricle is aesthetic; it has a minor role in hearing in that it helps
to gather sound. The aim of reconstruction of a traumatized auricle is to produce a
normal-looking ear. This is accomplished with a thorough understanding of the anatomy
and normal architecture of the auricle. The auricle is highly contoured elastic cartilage.
The contour depends on a highly adherent skin envelope, which is thin in the
anterolateral aspect and thicker and looser in the posteromedial aspect.
The two-dimensional outline of the ear is the most important feature in identifying it as
normal. A normal outline of the helical rim and root is the first feature the beholder's eye
identifies. Next is the outline of the concha and then the triangular fossa (1) (Fig. 62.1).
The next most important feature is the position of the auricle. The auricle should begin
one ear length posterior to the lateral orbital rim and extend from the level of the lateral
brow superiorly to the level of the nasal ala or upper lip inferiorly 5.5 to 6.5 cm. It should
incline 20 degrees posteriorly and protrude 1.5 to 2.0 cm from the mastoid process.

FIGURE 62.1. The ear with its parts and critical
proportions. (Modified from Tolleth H. A hierarchy of
values in the design and construction of the ear. Clin
Plast Surg 1990;17:193207, with permission.)



The third important feature is contour (Fig. 62.1). The helix starts in the upper third of the
concha at the midpoint of the ear, curves around opposite the intertragal notch (radius,
1.5 to 1.75 cm). From behind, the helix is relatively straight. The antihelix occupies about
20% of the width of the auricle at the helical root. The antihelix widens as it ascends to
form the anterior and posterior crura. The anterior crus is a tightly folded edge, and the
posterior crus is a wider, gentler curve. The concha forms 35% to 40% of auricular height
and 55% to 60% of the width. The outline of the concha (formed by the antihelix, anterior
crus, and tragus) provides a sense of depth. The tragus is about 3.0 cm high, protrudes
anteriorly, and adds a sense of depth to the meatus. The antitragus is expendable. The
lobule is 20% to 25% of the height of the auricle (1.3 to 1.5 cm) and has a variety of
shapes and sizes.
HEMATOMA
Hematoma (Fig. 62.2) is caused by blunt traumatic shearing forces, commonly from
wrestling and boxing. The shear force separates perichondrium from auricular cartilage,
tears blood vessels, and allows accumulation of blood between the skin-perichondrial
layer and the cartilage (2). The collected blood distorts the normal contour of the lateral
auricle, making a cauliflower ear. There is a history of recent trauma, possibly with pain,
paresthesia, and ecchymosis. Depending on the mechanism of injury, hearing loss or
temporal bone fracture is possible (2).

FIGURE 62.2. A: Auricular hematoma present for 1
month when the patient came to medical attention. B:
Incision in helical sulcus and raised flap show fibrosis
and neocartilage formation. C: Appearance after excision
of fibrous tissue and neocartilage. D: Stitch dressing.
Horizontal mattress through the ear sandwiched between
two dental rolls.



The aim of management of hematoma is to evacuate the hematoma, prevent
reaccumulation, and avoid complications. Cauliflower ear occurs when accumulated
subperichondrial blood causes formation of neocartilage (3,4). To avoid this, the
hematoma is drained through an incision in the helical sulcus (scaphoid hematoma) or
antihelical fold (conchal hematoma). Elevation of skin and perichondrium over the
hematoma allows evacuation and excision of any fibrocartilage along with excision of the
perichondrium (Fig. 62.2B,Fig. 62.2C). Removal of the perichondrium prevents
formation of neocartilage and cauliflower ear. A pressure dressing is applied for 7 to 10
days.
A variation allows wrestlers to continue training (5). A 5-mm incision is made directly
over the hematoma, and fluid is evacuated (Fig. 62.2D). A 3-0 silk suture sandwiches the
ear between two dental rolls, and is tied as a horizontal mattress. A mastoid dressing is
applied for 24 hours. The patient returns to wrestling with proper head gear augmented
with cotton on the involved side. The stitch dressing is removed in 10 to 14 days. This
approach works well for acute trauma. If there is neocartilage or dense fibrous clot, wide
exposure and complete removal is more efficacious.
LACERATIONS AND ABRASIONS
The aims of management of auricular lacerations and abrasions are to realign auricular
elements and prevent complications, such as infection, notching, and tattooing. After
induction of local anesthesia, abrasions and lacerations are antiseptically cleaned (2). For
road burn abrasions, vigorous scrubbing or jet irrigation is used to remove foreign
material and avoid tattooing. The ear is covered with an antibiotic ointment until
reepithelialized.
For simple lacerations, skin sutures are sufficient if cartilage is well aligned and there is
minimal tension on the skin sutures. The puzzle pieces of complex lacerations are pieced
together from known to unknown (6). Sutures at the helix, antihelix, and other known
structures generally align the unknown and make identification of missing parts obvious.
Reconstructing a normal helical shape is the priority. To avoid notching, everting rim
sutures are supported by underlying cartilage. Cartilage sutures align the edges without
overlap of the cartilage (6). They can be absorbable (6) or nonabsorbable (7), simple or
figure-of-eight sutures.
Wounds that are contaminated or more than 24 hours old are left open. Local wound care
and intravenous antibiotics are used to prevent chondritis. Stucker et al. (8) developed a
protocol for management of bite lacerations in the head and neck. All wounds are cleaned
with saline jet lavage. Animal bites less than 5 hours old are closed primarily. Animal
bites more than 5 hours old and human bites are closed with delayed primary closure
after several days of therapy with intravenous antibiotics and wound care. For human
bites, Stucker et al. use ticarcillin-clavulanate and continuous povidone-iodine soaks of
the wound. All patients with bite lacerations receive 10 days of antibiotics of ticarcillin-
clavulanate as an inpatient and amoxicillin and clavulanate mix as an outpatient.
Lacerations that traverse the external auditory canal can be difficult or impossible to
close. If circumferential, they carry a high risk of stenosis. Treatment entails canal
stenting with antibiotic-impregnated gauze and possible long-term (months) stenting with
a custom mold (2,6).
TOTAL AND SUBTOTAL AVULSION
General Concepts
Management considerations in avulsion injuries include (a) the usefulness of the avulsed
segment, (b) the condition of surrounding tissues, (c) the timing of surgery, (d) the best
use of remaining tissues, and (e) careful planning of reconstruction with a primary and a
secondary plan (Fig. 62.3). Whether to use the avulsed segment is a difficult decision.
The segment may be too mangled or too contaminated to be used safely. When the
segment is small, a better result can be obtained with nontraumatized auricular cartilage
graft or primary closure. Stucker et al. (8) showed that the avulsed segment bites should
not be reused as a simple composite graft, because there is a high failure rate. If the
segment is used for reconstruction, the cartilage is covered with vascularized tissue
without delay. Trauma to the surrounding structures can limit reconstructive possibilities.
If surrounding trauma is severe, it is better to allow initial healing before definitive
reconstruction.

FIGURE 62.3. Total avulsion of the auricle.



Tissue contamination and risk of infection can affect the timing of surgical intervention.
Surgical planning starts with identification of what is missing and what is available to
replace it. The previously discussed aesthetic hierarchy guides reconstructive priorities. A
backup plan is important for the first operation. This helps the surgeon to avoid burning
bridges that may have to be crossed later. Subtotal avulsion with even a minimal skin
attachment can survive with meticulous suturing of the ear to its normal position (9).
Venous congestion is common and must be aggressively controlled. Intravenous
antibiotics are administered (8).
Total Avulsion
The thin skin and contoured supple elastic cartilage of the auricle cannot be duplicated.
When total avulsion has occurred, successful microvascular reimplantation yields the best
results. Timing of presentation, presence of small vessels, and the need for vein grafts can
preclude this option (10). Postoperative care is likely to include anticoagulation and
lengthy hospitalization. Despite this, such a patient can consume fewer medical resources
than a patient whose initial care is less intensive but who needs revisions or staged
procedures (11).
If reimplantation is not possible, existing cartilage is used as a subsurface framework and
is covered by vascularized tissue. One of the following approaches can be used: (a) The
denuded cartilage is attached to the ear remnant and covered with a temporoparietal
fascial flap. Skin grafting of the lateral surface of the flap is performed later (12). (b) The
denuded cartilage attached to the remnant ear is covered with a postauricular
advancement flap. Three weeks later, the flap is detached, and skin grafting is performed
on the postauricular defect. (c) Posteromedial skin is removed, the cartilage is
fenestrated, the segment is reattached, and the posteromedial portion is placed against a
raw postauricular surface established by means of raising a postauricular flap (9) (Fig.
62.4). (d) Use the pocket principle (13). Dermabrasion is performed on the avulsed
segment, and the segment is attached to the remnant ear. This area is covered with a
postauricular skin advancement flap. The helical rim is unfurled with a traction stitch
from the rim through the postauricular skin. After 2 weeks, the anterolateral segment and
helical rim are removed from the pocket and allowed to epithelialize. The following
week, the posteromedial segment is removed and the skin is resutured at the postauricular
sulcus to allow this segment to epithelialize. Brent (9) recommends not detaching the
posteromedial segment for several months to allow better vascularization. After
detachment, skin grafting can be performed.

FIGURE 62.4. A: Posteromedial portion of avulsed
segment after posterior skin has been removed and
cartilage fenestrated. B: Avulsed segment reattached and
sutured to a raw postauricular area made by means of
elevation of mastoid flap. (Modified from Brent B.
Reconstruction of the auricle. In: McCarthy JG, ed.
Plastic surgery. Philadelphia: WB Saunders, 1990:2119
2152, with permission.)



If successful, the last two methods have the advantage of restoring normal contour to the
ear because both the tightly adherent skin and cartilage are replaced. Methods that cover
normal cartilage with thick postauricular skin or a temporoparietal fascial flap do not
obtain the same normal contour. All these methods can suffer from some degree of
cartilage necrosis (shrinkage).
A controversial option for total or near-total avulsion is replacement of the avulsed
segment as a composite graft. This entails aggressive postoperative care, including
cooling the auricle, administration of dextran, heparin, and antibiotics, along with stab
incisions over the edematous and cyanotic areas (14). Most surgeons find that a large
composite graft is unlikely to succeed (2,9), particularly for a human bite, because of
poor blood supply to the contaminated area (8).
Partial Avulsion
Helical Rim
The helical rim is an important structure for conferring a visual impression of a normal
ear (1). Defects less than 2 cm in area are best managed by means of helical rim
advancement (Fig. 62.5) (15). In one technique an incision is made in the helical sulcus
and is carried through the anterolateral skin and cartilage but not the posteromedial skin
(15). An alternative is to include include cartilage and both layers of skin in the incision
(16). The incision is carried into the lobule to allow use of this skin in the advancement
(16). If posterior skin is left intact, it is widely dissected from the rest of the
perichondrium. Additional length can be gained by means of V-to-Y advancement of the
helical root with an anterior skin attachment. To avoid cupping, a small Burow triangle
may have to be removed. Although this technique leaves the ear slightly smaller, the
contour is normal, and the size discrepancy generally is not a problem because both ears
seldom are seen at the same time.

FIGURE 62.5. Antihelical rim advancement. A: Failed
composite graft. B: Defect after dbridement of
composite graft with rim advancement design. Extension
into lobule is evident. C: Elevation of postauricular skin
from cartilage. Wide elevation is performed to allow flap
movement. D: Final result.



For a larger helical defect, a tube flap can be made from postauricular skin and
transferred to the auricle in a multistage procedure (17). Other strategies include
harvesting ipsilateral or contralateral auricular cartilage and covering the area with a
preauricular transposition flap (7) (superior defects) or postauricular skin in a two-stage
reconstruction (Fig. 62.6) (17).

FIGURE 62.6. Defects limited to helical rim.



Defects of the Upper Third of the Ear
Small defects of the helical rim are best repaired by means of helical rim advancement.
For larger defects, if the avulsed segment can be used, it can be sewn as a composite graft
with or without one of the techniques described earlier to increase viability. Variables
such as graft condition, surrounding tissues, and time between avulsion and
reimplantation affect graft survival. In general, a successful composite graft is less than
1.5 to 2.0 cm in area (2,9). Even with these smaller grafts, vascular augmentation
techniques, such as the pocket principle (13) or the technique of Baudet (9), should be
considered. Because of poor vascularity, highly contaminated grafts should not be simply
sutured on (8), but one of the vascular augmentation techniques should be performed.
Defects without a usable avulsed segment are reconstructed by means of replacement of
the missing components with contralateral conchal cartilage or rib cartilage covered by a
vascularized skin flap. Vascularized skin is obtained with a superiorly based preauricular
transposition flap or postauricular tunneled flap (18) (Fig. 62.7). Brent (17) recommends
repairing major losses with a technique described by Adam. Contralateral conchal
cartilage is buried in a postauricular skin pocket. It is later elevated, and the medial
surface is skin grafted. The conchal outline is made with construction of an inferior crus.
Parallel incisions superior and inferior to the intended inferior crus are made into a
bipedicled tubed flap. The tubed flap is sutured together as a valise handle, and skin
grafts are applied to the raw areas.

FIGURE 62.7. Repair of superior defect with the
Converse tunnel method. A: Ear held against
retroauricular skin. The superior border of defect is
marked as a proposed incision. The incision is made, and
posteromedial auricle skin is sewn to the anterior
retromastoid incision to make a tunnel. B: Cartilage graft
inserted after undermining of postauricular flap. Lateral
incision is closed. C: Second stage. After 4 weeks the
auricle is released, and skin grafts are applied to the raw surfaces. (Modified from
Converse JM. Reconstruction of the auricle. Plast Reconstr Surg 1958;22:154, with
permission.)



Defects of the Middle Third of the Ear
Small defects of the middle third of the ear can be closed primarily with a wedge or star
excision. A small amount of height is sacrificed to maintain normal contour. If the
avulsed segment cannot be used, cartilage graft is covered by vascularized tissue (Fig.
62.8). Cartilage from the contralateral ear usually is used. Vascularized tissue from a
postauricular skin flap is used either as a pocket (advancement) or transposition flap
(7,17) (Fig. 62.9).

FIGURE 62.8. Middle-third defect without usable
segment. A: Original defect. B: The first stage is suture
of a retroauricular flap to the anterolateral skin. C: In the
second stage, the flap is released from the mastoid
process and wrapped around the contralateral conchal
cartilage graft. D: Final results. Normal contour is
difficult to attain.



FIGURE 62.9. Defects limited to the middle and upper
third of the ear.



Defects of the Lower Third of the Ear
For extensive lower-third defects Brent (17) begins with insertion of a contralateral
subcutaneous cartilage graft in the proposed site of the neolobule. Six weeks later
elevation and skin grafting are performed on the posteromedial segment. Other
reconstructive methods (19) involve a local skin flap folded on itself or with skin grafting
of the posteromedial side. Subtotal lobular defects usually are partial avulsion or an
earring clefting injury. Partial avulsion can be managed with rotation of the available
tissues and closure of the wound as a wedge defect. Brent (17) describes using the
concept of antihelical rim advancement to rotate the rim and lobule inferiorly to make
primary wedge closure possible.
Earring clefting injuries are common. If the patient desires to keep the ear pierced, the
adjacent flap technique described by Pardue (20) (Fig. 62.10) is a good option.
Otherwise, wedge excision with or without a means to break up the suture line, such as Z-
plasty (7), should be chosen (Fig. 62.11).

FIGURE 62.10. Pardue adjacent flap technique to
maintain an epithelialized track. A: Incision adjacent to
one side of cleft while other side is freshened. B:
Adjacent flap rolled to maintain epithelialized tract. C:
Cleft closed with small Z-plasty. (Modified from Pardue
AM. Repair of torn earlobe with preservation of the
perforation for an earring. Plast Reconstr Surg
1973;51:472, with permission.)



FIGURE 62.11. Defects of the lower third of the ear.



FROSTBITE
Frostbite is a localized tissue injury caused by continued exposure to subzero
temperatures. Injury is increased by factors that decrease local blood flow, such as
nicotine consumption and peripheral vascular disease, as well as environmental factors,
such as wind (wind chill factor), lack of protective clothing, and dampness of the body
tissue (21). Although the pathophysiologic mechanism of frostbite is incompletely
understood, injury to the blood vessels is more extensive than is parenchymal injury. The
early tissue response is separation of the endothelial cells from one another and from the
internal elastic lamina. This mechanism leads to aggregation of platelets and leukocytes
and to extravasation of erythrocytes and sludging (22). Pharmacotherapy aimed at
decreasing microvascular injury is under investigation (23). Initial symptoms are tingling,
pain, and burning, which are replaced by numbness and hardening of the tissue. Initial
damage is classified as superficial or deep. In superficial frostbite, the surface is frozen,
but the deeper structures are pliable. In deep frostbite, the entire ear is hard.
After therapy for hypothermia, treatment centers on rapid rewarming, avoidance of
mechanical trauma, and delayed dbridement. Pharmacotherapy for the microvasculature
and antibiotics and tetanus prophylaxis are administered. Rapid rewarming is
accomplished by means of immersing the affected part in a warm-water bath at 40C to
42C (104F to 108F) until the most distal part is flushed (about 15 to 30 minutes). For
the ear, Sessions et al. (24) recommend surrounding the ear with wet sterile pledgets
maintained at a temperature of 38C to 42C. This is painful, and appropriate analgesics
are administered. After rewarming, swelling and blister formation occur, and care is mild
cleaning and avoidance of dependency and further mechanical trauma. This can be
followed by mummification and autoamputation of deep frostbite. Heggers et al. (25)
advocate the use of topical aloe vera (thromboxane synthetase inhibitor), systemic
ibuprofen (cyclooxygenase inhibitor), and penicillin along with dbridement of white
blisters (containing thromboxane A
2
and prostaglandin F
2
) but not hemorrhagic blisters.
Most authors do not advocate blister dbridement.
BURNS
Burns of the auricle usually are part of more extensive facial burns and are managed by a
burn team. The otolaryngologist considers possible airway involvement in the burn
mechanism. Burns are divided into first-, second- (superficial or deep), and third-degree
burns. Burn depth determines healing. Reepithelialization is outgrowth of epidermal cells
from dermal skin appendages. The more appendages that remain, the more rapid is
reepithelialization and the less is the scarring that occurs.
First-degree burns involve epithelium. Superficial second-degree burns involve the
epithelium and superficial dermis and spare epidermal appendages. These burns are red
with capillary refill and pinprick sensation is intact. Second-degree burns can blister.
These burns heal without scarring. The aim of treatment is pain control and avoidance of
infection. Deep second-degree (may involve entire dermis) and third-degree (into
subcutaneous fat) burns can be difficult to differentiate. The ear may be white in a deep
second-degree burn and white to black in a third-degree burn. Pinprick and capillary refill
always are absent in third-degree burns and are variable in deep second-degree burns.
Avoiding further tissue damage and chondritis is the goal of management of second- and
third-degree burns. The ear is washed twice a day with antibacterial soap, and mafenide is
applied to penetrate eschar. Mechanical trauma is avoided by use of a doughnut.
Exposed cartilage is covered with vascularized tissue (26).
KELOIDS
Keloids are an abnormal tissue response to trauma. These fibrous tumors have excessive
collagen deposition. They extend beyond the original wound (hypertrophic scars do not).
Keloids usually occur among dark-skinned persons 10 to 30 years of age. The prevalence
among blacks and Hispanics may be as high as 16%. There is a familial tendency (27,28).
The pathophysiologic mechanism of keloids is being elucidated. Fibroblasts or
myofibroblasts appear to be essential (29). Most of the keloid is overabundant
extracellular matrix (mostly glycoproteins and water). Scanning electron microscopic
examination shows randomly aligned collagen bundles (27).
Common treatments involve combinations of steroid injections, surgery, radiation,
pressure, cryotherapy, interferon injection, and application of silicone gel sheeting.
Antihistamines can decrease pruritus (27,28). Intralesional steroid injection
(triamcinolone, 10 to 20 mg/mL) is variably successful. The injections can be started
preoperatively, intraoperatively, or postoperatively, usually every 3 to 4 weeks. Side
effects include skin or subcutaneous fat atrophy, hypopigmentation, telangiectasia, and
ulceration. Although irradiation can be effective, most physicians are reluctant to use this
treatment on young patients (27,28).
Ear keloids usually follow ear piercing. They occur typically on the posteromedial
surface of the ear (27). Management of earlobe keloids is surgical removal followed by
steroid injection. Surgery alone has a high recurrence rate. The following methods have a
recurrence rate less than 5%: (a) The keloid is surgically removed, and the skin is sutured
with 6-0 nylon; no deep stitches are made. Three weeks postoperatively, the site is
injected with 0.1 to 0.2 mL of 20 mg/mL triamcinolone. Injection is repeated twice at 4-
week intervals. The only complication among 31 patients was one case of depigmentation
(30). (b) After surgical excision, skin is approximated with 6-0 nylon. A large clip-on
earring is applied to the incision for 8 hours a day for 3 months along with
flurandrenolide tape. The sutures are removed 14 days after the surgical procedure. (c)
The keloid is excised with a carbon dioxide laser, and steroid injections are used
intraoperatively and postoperatively. Wound healing is by secondary intention. There
were no recurrences among 16 patients. Regardless of treatment method, postoperative
monitoring and treatment are needed for a successful outcome.

HIGHLIGHTS
Thorough understanding of the normal anatomy and aesthetics
of the auricle precedes reconstruction.
Management of hematoma involves drainage of the blood
between perichondrium and cartilage and use of pressure
dressings to prevent reaccumulation. Inadequate or delayed
treatment can cause neocartilage formation and cauliflower ear.
Closure of complex lacerations begins with identification and
reapproximation of known landmarks.
Management of avulsion begins with assessment of the
usefulness of the severed part. If the part is to be used as a graft,
revascularization must proceed without delay with vascular
augmentation techniques to increase graft survival.
When the avulsed segment is not useful, the defect is
reconstructed with contralateral conchal cartilage covered by a
retromastoid flap.
Total avulsion is best managed by means of microvascular
anastomosis.
Tissue affected by human bite avulsion must not be reattached
in simple composite grafts.
Management of frostbite is rapid rewarming with warm soaks
(38 to 42C) until the ear is flushed.
Management of a burned auricle is directed at prevention of
chondritis and further tissue loss.
Earlobe keloids are managed by means of excision followed by
steroid injection or use of a pressure earring.
CHAPTER REFERENCES
1. Tolleth H. A hierarchy of values in the design and construction of the ear. Clin Plast Surg
1990;17:193207.
2. Lawson W. Management of acute trauma. In: Lucente FE, Lawson W, Novick NL, eds. The
external ear. Philadelphia: WB Saunders, 1995:174187.
3. Ohlsen L, Skoog T, Sohn SA. The pathogenesis of cauliflower ear. Scand J Plast Reconstr Surg
1975;9:3439.
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1985;111:161.
5. Schuller DE, Dankle SD, Strauss RH. A technique to treat wrestlers' auricular hematoma without
interrupting training or competition. Arch Otolaryngol Head Neck Surg 1989;115:202.
6. Templer J, Renner GJ. Injuries of the external ear. Otolaryngol Clin North Am 1990;23:1003
1018.
7. Lacher AB, Blitzer A. The traumatized auricle: care, salvage and reconstruction. Otolaryngol Clin
North Am 1982;15:225239.
8. Stucker FJ, Shaw GY, Boyd S, et al. Management of animal and human bites in the head and
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9. Brent B. Reconstruction of the auricle. In: McCarthy JG, ed. Plastic surgery. Philadelphia: WB
Saunders, 1990:21192152.
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11. Cho BH, Ahn HB. Microsurgical replantation of a partial ear, with leech therapy. Ann Plast Surg
1999;43:427429.
12. Jenkins AM, Finucan T. Primary nonmicrosurgical reconstruction following ear avulsion using the
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14. Bernstein L, Nelson RH. Replanting the severed auricle: an update. Arch Otolaryngol
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15. Antia NH, Buch VI. Chondrocutaneous advancement flap for the marginal defect of the ear. Plast
Reconstr Surg 1967;39:472.
16. Calhoun KH, Slaughter D, Kassir R, et al. Biomechanics of the helical rim advancement flap.
Arch Otolaryngol Head Neck Surg 1996;122:11191123.
17. Brent B. The acquired auricular deformity: a systemic approach to its analysis and reconstruction.
Plast Reconstr Surg 1977;59:475485.
18. Converse JM. Reconstruction of the auricle. Plast Reconstr Surg 1958;22:154.
19. Brent B. Earlobe construction with an auriculo-mastoid flap. Plast Reconstr Surg 1976;57:389
391.
20. Pardue AM. Repair of torn earlobe with preservation of the perforation for an earring. Plast
Reconstr Surg 1973;51:472.
21. Coffman JD. Cutaneous changes in peripheral vascular disease. In: Fitzpatrick TB, ed.
Dermatology in general medicine, 4th ed. New York: McGraw-Hill, 1993:20922093.
22. Marzella L, Jesudass RR, Manson PN, et al. Morphologic characterization of acute injury to
vascular endothelium of skin after frostbite. Plast Reconstr Surg 1989;83:67.
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2000;48:171178.
24. Sessions DG, Stallings JO, Mills WJ, et al. Frostbite of the ear. Laryngoscope 1971;81:1223.
25. Heggers JP, Robson MC, Manavalen K, et al. Experimental and clinical observations on frostbite.
Ann Emerg Med 1987;16:1056.
26. Bhandari PS. Total ear reconstruction in post burn deformity. Burns 1998;24:661670.
27. Murray JC. Scars and keloids. Dermatol Clin 1993;11:697707.
28. Berman B, Bieley HC. Adjunct therapies to surgical management of keloids. Dermatol Surg
1996;22:126130.
29. Sherris DA, Larrabee WB, Murakami GS. Management of scar contractures, hypertrophic scars,
and keloids. Otolaryngol Clin North Am 1995;28:10571067.
30. Shons AR, Press BH. The treatment of earlobe keloids by surgical excision and postoperative
triamcinolone injection. Ann Plast Surg 1983;10:480.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

63 LARYNGEAL TRAUMA
Head & Neck SurgeryOtolaryngology
63




LARYNGEAL TRAUMA
STEVEN D. SCHAEFER
SCOTT P. STRINGER

S.D. Schaefer: Department of Otolaryngology, New York Eye and Ear Infirmary, New York, New York.
S.P. Stringer: Department of Otolaryngology, University of Florida College of Medicine, Gainesville,
Florida.


Pathophysiology of Laryngeal Injuries
Blunt Trauma
Penetrating Trauma
Diagnosis and Evaluation
History
Physical Examination
Radiologic Evaluation
Management
Emergency Care
Treatment Decision Making
Medical Treatment
Surgical Treatment
Grafting
Stents
Cricotracheal Separation
Severed Recurrent Laryngeal Nerve
Complications
conclusion
Chapter References
Timely, proper management of injury to the larynx is essential to preserve the patient's
life, airway, and voice. Each case of external laryngeal trauma presents a unique set of
problems, but despite the diversity of injuries, specific management guidelines can be
applied to each situation. Adhering to such an approach ensures the best possible
outcome after blunt or penetrating external laryngeal trauma.
PATHOPHYSIOLOGY OF LARYNGEAL INJURIES
Blunt Trauma
Blunt trauma to the larynx is caused mainly by motor vehicle accidents, personal assaults,
or sports injuries. Although the mandible and sternum normally protect the larynx, the
neck can be hyperextended during the trauma, which allows the laryngeal skeleton to be
crushed between the impinging object and the cervical vertebral column. With a
moderate blow to the larynx, the momentum of the vocal folds causes a shearing effect
between the vocalis muscle and the internal perichondrium. The result is injuries such as
endolaryngeal mucosal tears, edema, or hematoma. More severe trauma produces
fractures of the laryngeal cartilages and disruption of the laryngeal ligaments.
Subluxation or dislocation of the arytenoid cartilage can produce a fixed vocal fold.
Unilateral injury to the recurrent laryngeal nerve often is associated with cricoarytenoid
joint injuries owing to the proximity of the recurrent laryngeal nerve to the cricoid
cartilage. Fractures of the cricoid cartilage can occur alone or with other injuries,
especially after lower cervical trauma. As the only complete ring of the airway, the
cricoid cartilage is essential in airway maintenance. Loss of its structural integrity can
cause airway obstruction.
The so-called clothesline injury that occurs in association with blunt laryngeal trauma
deserves special attention because of its severity. This injury typically occurs when the
neck of someone riding a motorcycle or snowmobile strikes a stationary object such as a
wire fence or tree limb. The transfer of such a large amount of force to the neck crushes
the laryngeal cartilages and can cause cricotracheal separation. The airway is held
together precariously by the intervening mucous membrane. Bilateral injury to the
recurrent laryngeal nerve often is associated with cricotracheal separation.
Associated structures also can be injured during blunt cervical trauma. Fractures of the
hyoid bone and associated epiglottic injuries can cause airway obstruction. The greater or
lesser cornu of the thyroid cartilage can lacerate the pharyngeal mucosa as it is pressed
against the cervical vertebrae. Sex and age differences among adults have been
hypothesized as leading to different types of injuries after blunt trauma. Women are
considered more likely to incur supraglottic injuries than are men because they have long,
thin necks. Elderly persons have been described as being at higher risk of sustaining
comminuted laryngeal fractures than are younger adults because older persons have more
calcification of the larynx. Neither of these hypotheses have been verified with clinical
observation (1).
Blunt trauma tends to affect the larynx of a child differently from that of an adult. The
larynx in children is situated higher in the neck and is better protected by the mandible
than it is in adults. Laryngeal fractures are less common because of the elasticity of the
pediatric cartilaginous skeleton; however, the lack of extensive fibrous tissue support and
the relatively loose attachments of the mucous membranes increase the likelihood of soft-
tissue damage in children. The cricothyroid membrane is narrow in children, and this
feature decreases the likelihood of laryngotracheal separation (2). Manual strangulation
produces different laryngeal injuries because the applied force is fairly static and of low
velocity. This can cause multiple cartilaginous fractures without immediate mucosal
laceration, submucosal hematoma, or marked displacement of the fractures (3).
Penetrating Trauma
Knife and gunshot wounds are primarily responsible for penetrating trauma. Injuries vary
from minor lacerations to severe disruption of the cartilage, mucosa, soft tissue, nerves,
and adjacent structures. The amount of energy absorbed by the cervical tissues in a
gunshot wound, and therefore the degree of injury, is directly related to the velocity and
mass of the wounding missile (4). Gunshot wounds are more likely than knife wounds to
be associated with severe tissue damage. Wounds from high-velocity military weapons or
hunting rifles are especially severe. Death is caused by complete disruption of the larynx,
massive soft-tissue edema, or associated neurovascular injuries. Most injuries to civilians
from penetrating trauma tend to be limited to the path of the missile because they are
caused by lower-velocity bullets or stabbing. Knife wounds cause less peripheral soft-
tissue damage than gunshot wounds and are cleaner, but it is difficult to determine depth
of penetration. Injuries to deep structures, such as the thoracic duct, cervical nerves, great
vessels, and viscera, can occur well away from the entrance wound.
DIAGNOSIS AND EVALUATION
History
Any patient with anterior neck trauma is considered to have an upper airway injury. The
classic symptoms of laryngeal trauma include hoarseness, laryngeal pain, dyspnea, and
dysphagia (Table 63.1). It is surprising that no single symptom seems to correlate well
with the severity of injury (1). When the laryngeal lumen is severely compromised,
aphonia and apnea occur, signifying the need for immediate establishment of an
alternative airway.

TABLE 63.1. DIAGNOSIS LARYNGEAL
TRAUMA



Physical Examination
After trauma, a thorough physical examination of the neck is needed to identify
associated neurovascular injuries. Cervical spinal injuries must be ruled out for all
patients with neck trauma. Active bleeding, expanding hematoma, bruits, and the loss of
pulses are signs of vascular injury. The usual signs of laryngeal trauma include stridor,
hemoptysis, subcutaneous emphysema, and tenderness or deformity of the laryngeal
skeleton. The presence of tenderness to palpation helps to differentiate an acute laryngeal
fracture from an old deformity. The type of stridor can suggest the location of the lesion.
Inspiratory stridor typically indicates partial supraglottic airway obstruction, as might
occur from edema, hematoma, foreign body, soft-tissue injury, or cartilaginous fractures.
Expiratory stridor may portend a lower airway abnormality caused by a tracheal injury.
Combined inspiratory and expiratory stridor suggests partial obstruction at the level of
the glottis.
Cervical subcutaneous emphysema is associated with loss of the integrity of the upper
aerodigestive tract. The amount of air can range from slight soft-tissue emphysema to
massive pneumomediastinum. Associated soft-tissue derangements of the larynx can
produce in a ball-valve effect that forces massive amounts of air into the neck and chest
as well. Further compromise of the airway can be caused by tracheal displacement or
tension pneumothorax.
Although a patient who has sustained cervical and multisystem trauma often cannot be
moved into position for indirect laryngoscopy, direct fiberoptic laryngoscopy usually
allows adequate laryngeal examination. The larynx is examined for mobility of the vocal
folds, hematoma, lacerations, and airway patency. Rigid esophagoscopy is the best way
to examine the hypopharynx and esophagus when indicated (5).
Radiologic Evaluation
Computed tomography (CT) has replaced soft-tissue radiography, xerography,
polytomography, and laryngography as the best examination for evaluating laryngeal
trauma (6,7). Laryngography is contraindicated when the airway is unstable, because
acute obstruction can occur. Computed tomography is most useful when the results
influence treatment, as opposed to documentation of an obvious injury when management
will not be changed. Two groups of patients do not need CT for diagnostic evaluation: (a)
Patients with obvious fractures, large endolaryngeal lacerations, or severe penetrating
trauma most often need tracheotomy, direct laryngoscopy, and open exploration. For a
small select group of these patients, CT can be of benefit in planning structural repair. (b)
Patients with minimal anterior neck trauma and normal physical findings do not benefit
from CT. All patients in the intermediate group undergo CT to assess the extent of
laryngeal injury. When used, CT helps to confirm indirect or flexible fiberoptic
laryngoscopic findings, to detect cartilage fractures that are not clinically apparent, to
assess poorly visualized areas, such as the subglottic and anterior commissure regions,
and to identify associated cervical injuries (6).
Special radiographic studies can be useful in identifying injuries associated with
laryngeal trauma, especially with penetrating trauma. Cervical arteriography shows
vascular injury, and pharyngeal and esophageal tears can be identified with the use of a
barium swallow examination. Radiographs of the cervical spine are needed to rule out
vertebral injury. Particular care is taken to visualize the entire cervical spine to avoid
missing injuries of the lower cervical vertebrae.
MANAGEMENT
Figure 63.1 shows a management protocol for acute injuries to the larynx. There are two
primary goals in the management of acute laryngeal traumapreserving life by
maintaining the airway and restoring function as judged by lack of dependence on a
tracheostomy and by voice quality. These goals are universally accepted, but the most
appropriate methods to achieve them are controversial (8).

FIGURE 63.1. Management protocol for management of
acute injury to the larynx. (From Schaefer SD. The
treatment of acute external laryngeal injuries. Arch
Otolaryngol Head Neck Surg 1991;117:35, with
permission.)



Emergency Care
The initial evaluation and treatment of a trauma patient consist of airway preservation,
cardiac resuscitation, control of hemorrhage, stabilization of neural and spinal injuries,
and a systematic investigation for injuries to other organ systems (Table 63.2).
Controversy exists regarding the best way to establish an alternative airway in the
presence of laryngeal trauma. Intubation in this setting is hazardous. The attempted
endotracheal intubation of a traumatized larynx can cause iatrogenic injury or the loss of
an already precarious airway (7). If orotracheal intubation is performed in this setting, it
must be done under direct visualization by experienced personnel using a small
endotracheal tube (9). These requirements cannot always be met when laryngeal trauma
is present. Whereas orotracheal intubation can be used to treat many patients without
adverse outcome, tracheotomy is more effective in completely preventing the loss of or
damage to the airway. For these reasons, many authors strongly recommend tracheotomy
with local anesthesia rather than endotracheal intubation for persons who have sustained
laryngeal trauma and need an alternative airway (1,10,11). Patients with minimal
laryngeal injury, documented with fiberoptic laryngoscopy and CT, can safely undergo
careful endotracheal intubation if it is needed to manage other injuries. Such intubation is
performed by a highly experienced physician to avoid further injury to the larynx.

TABLE 63.2. EMERGENCY
CARELARYNGEAL TRAUMA



A child with a traumatized larynx presents a special case because it usually is difficult to
perform tracheotomy under local anesthesia in this situation. Inhaled anesthesia with
spontaneous respirations is used to achieve bronchoscopic intubation, which allows direct
visualization of laryngeal injuries and prevents additional iatrogenic injury. After
successful bronchoscopy, tracheotomy can be performed as needed (2).
Treatment Decision Making
Management is divided into medical and surgical treatment according to the extent of
injury as determined at physical examination and CT (Table 63.3). The decision to treat a
patient medically or surgically is determined by the likelihood that the injury will resolve
without surgical intervention. The following conditions are likely to resolve
spontaneously without serious sequelae (6,8,12): edema, small hematoma with intact
mucosal coverage, small glottic or supraglottic lacerations without exposed cartilage,
single nondisplaced thyroid cartilage fractures in a stable larynx. Some evidence,
however, suggests that the repair of even single nondisplaced angulated fractures can
prevent subtle vocal changes, as shown by acoustic impedance (13). Injuries likely to
necessitate open laryngeal exploration and repair include lacerations involving the free
margin of the vocal fold, large mucosal lacerations, exposed cartilage, multiple and
displaced cartilage fractures, avulsed or dislocated arytenoid cartilages, and vocal fold
immobility (1,14,15,16 and 17).

TABLE 63.3. TREATMENT LARYNGEAL
TRAUMA



Injuries likely to necessitate open exploration, primary repair, and endolaryngeal stenting
include disruption of the anterior commissure, multiple and displaced cartilage fractures,
and multiple and severe endolaryngeal lacerations. Stenting is indicated in the
management of these injuries to prevent loss of the normal scaphoid shape of the anterior
commissure, to stabilize severely comminuted fractures or lacerations, and to prevent
endolaryngeal stenosis. Penetrating trauma is more likely to necessitate open exploration
than is blunt trauma.
Medical Treatment
The goals of adjuvant therapy are to eliminate further injury and to promote rapid
healing. The clinical course after blunt trauma to the neck is uncertain; therefore
hospitalization for at least 24 hours is recommended to observe for signs of progressive
airway compromise. Preparations are made for possible emergency tracheotomy.
Bed rest with elevation of the head of the bed for several days helps resolve laryngeal
edema. A period of voice rest can minimize further edema or reduce the progression of a
hematoma or subcutaneous emphysema. The use of cool, humidified room air helps
prevent crust formation in the presence of mucosal damage and transient ciliary paralysis.
Additional oxygen is not needed unless indicated by arterial blood gas values and can
even be harmful, especially in the care of older patients who are susceptible to carbon
dioxide retention.
Systemic corticosteroids have been used sporadically in the management of laryngeal
trauma in an effort to reduce edema and subsequent fibrosis, but no convincing clinical or
experimental evidence supports use of this therapy. If used, corticosteroids are most
likely to be of benefit in the first few hours after injury. If there is evidence of a mucosal
tear or laceration, antibiotics can be useful as prophylaxis against infection.
A patient with a laryngeal injury is restricted at first to a clear liquid diet with intravenous
supplementation as necessitated by other injuries. Nasogastric feedings usually are
unnecessary, and passage of a nasogastric tube can worsen the injury. Prolonged use of a
nasogastric tube can traumatize the posterior larynx and promote gastric acid reflux. The
use of antacids and H2 histamine blocking agents can prevent the development of reflux
laryngitis among patients in the hospital and possibly among those who have undergone
tracheotomy. Patients with hypopharyngeal tears are given nothing by mouth initially.
Surgical Treatment
The optimal timing of endoscopic evaluation and surgical management of laryngeal
trauma is controversial (1,8,14,15,16 and 17). Some experts assume that waiting several
days after trauma allows the edema to resolve so that endolaryngeal lacerations can be
better identified and approximated (11,14,18). Conversely, early exploration offers the
opportunity for complete assessment of the injury and may result in a lower postoperative
infection rate, quicker healing, less granulation tissue, and less scarring. Results of
several large series of cases of laryngeal trauma suggest that early surgical intervention is
more effective in allowing accurate identification of mucous membrane, muscle, and
cartilage injuries, which can be repaired primarily, than is relying on healing by
secondary intention or grafting (1,8,10,15).
Endoscopy is used to ascertain the extent of injury to the larynx and adjacent
aerodigestive tract when further surgical management is being considered. A thorough
direct laryngoscopic examination is performed in which the entire larynx and
hypopharynx are visualized. If dislocated arytenoid cartilage is found, endoscopic
attempts at relocation are attempted. Bronchoscopy also is used to evaluate the subglottis
and trachea. Esophagoscopy is performed to rule out unsuspected esophageal perforation.
When injuries that clearly necessitate surgical management are identified at endoscopy,
open exploration is performed immediately.
The extent of injury found at endoscopy or open exploration determines the extent of
surgical therapy. It may be as limited as tracheotomy to establish an airway or as
extensive as open reduction and internal fixation with stenting. Endoscopic or CT
evidence of laceration of the mucous membrane, exposed cartilage, immobility of the
vocal folds, or displaced or comminuted fractures of cartilage are indications for open
exploration. Open reduction and fixation of cartilage fractures is definitely preferable to
closed reduction over a bronchoscope and subsequent placement of a stent because of the
difficulty of obtaining an adequate reduction in a closed manner and because the dynamic
nature of the stresses on the larynx necessitate continued fixation to provide stability (8).
In the management of severe injuries, such as large mucosal lacerations involving the
anterior commissure, comminuted cartilage fractures, and avulsion of the arytenoid
cartilage, open exploration through a laryngofissure or thyrotomy with stenting is
indicated.
Exploration is performed through a horizontal skin incision in a skin crease at the level of
the cricothyroid membrane. Subplatysmal flaps are elevated superiorly to the level of the
hyoid bone and inferiorly to just below the cricoid cartilage. The incision can be extended
to explore and repair associated neural, vascular, or visceral injuries. The infrahyoid strap
muscles are separated in the midline and retracted laterally to expose the laryngeal
skeleton and fractures. The thyroid cartilage is incised at the midline, and the endolarynx
is entered through the cricothyroid membrane. Under direct vision, the incision is
extended superiorly through the anterior commissure to the thyroid membrane. The entire
endolarynx is examined to identify the extent of the injury (Fig. 63.2, Fig. 63.3). The
arytenoid cartilages are palpated to assess their position and mobility.

FIGURE 63.2. Fracture of thyroid cartilage.



FIGURE 63.3. Laceration of true vocal fold and
hematoma of false vocal fold.



All mucous membrane, muscle, and cartilage with a viable blood supply are preserved
and restored to their original position. Because it is the primary factor responsible for
formation of granulation tissue and fibrosis, exposed cartilage must be covered primarily.
Failure to do so necessitates grafting and healing by secondary intention. Lacerations are
meticulously approximated with 5-0 or 6-0 absorbable suture material (Fig. 63.4).
Mucosal advancement flaps may be needed to relieve tension on suture lines and to
achieve complete cartilage coverage.

FIGURE 63.4. Repair of lacerations.



Cartilaginous fractures are fixed with wire, nonabsorbable suture, or miniplates.
Miniplates are used only when all screws can be securely threaded into cartilage, or they
can become dislodged. Small fragments of cartilage with no intact perichondrium are
removed to prevent chondritis. The anterior margin of each true vocal fold is sutured to
the thyroid cartilage or its external perichondrium at the thyrotomy site to reconstitute the
anterior commissure (Fig. 63.4). If the anterior commissure is devoid of epithelium, a
preformed keel or reinforced polymeric silicone sheeting can be placed to prevent web
formation. The thyrotomy is closed with wire (Fig. 63.5), nonabsorbable suture, or
miniplates. If part of the anterior cricoid ring is lost, suturing the infrahyoid strap muscles
into the defect can help maintain the airway and voice.

FIGURE 63.5. Wire closure of fractured thyroid
cartilage. Nonabsorbable synthetic sutures can be used as
a substitute for wire in lesser injuries.



Grafting
Adhering to the principles of conservation of normal anatomic relations and immediate
surgical management makes the need for a graft rare. Mucous membrane or skin grafts
have been used to cover areas of exposed cartilage that cannot be closed primarily;
however, these wounds must heal by secondary intention, which causes greater scar
formation than with primary closure. In the rare situation in which a graft is needed,
mucous membrane, dermis, and split-thickness skin are suitable. Mucous membrane most
closely resembles the normal endolaryngeal epithelium, but use of this tissue carries high
donor-site morbidity and necessitates entering the oral cavity. Grafting never is a
substitute for careful closure of laryngeal lacerations.
Stents
Laryngeal stents can be used initially for internal fixation devices and thereafter prevent
endolaryngeal scarring and maintain the internal configuration of the larynx. Although
the presence of a stent can increase the risk of infection and formation of granulation
tissue, the clinical findings sometimes dictate stenting (19). Multiple cartilaginous
fractures that cannot be stabilized adequately with open reduction and internal fixation
and extensive lacerations involving the anterior commissure are specific indications for
the use of stents. In the presence of a stable laryngeal skeleton with an intact anterior
commissure before thyrotomy, stenting is not needed. Massive mucosal injuries may
necessitate stenting to prevent mucosal adhesions (Fig. 63.6). Stents alone, however, are
not a substitute for primary closure of mucosal lacerations and careful reduction and
internal fixation of fractures (1,8).

FIGURE 63.6. Fixation of endolaryngeal stent using
nonabsorbable sutures.



The stent is fixed in the larynx in such a way that it moves with the larynx during
swallowing. The stent can be consistently and easily recovered by means of endoscopy
alone. A useful method is to pass a heavy, nonabsorbable suture through the stent and the
larynx at the level of the laryngeal ventricle and another at the cricothyroid membrane.
These are tied over buttons outside the skin. There is some controversy about how long to
leave a stent in place. The desired laryngeal stabilization must be achieved and scar
formation prevented, but the risk of infection and wound necrosis associated with
prolonged stenting must be considered. If all wounds have been closed carefully and the
fractures effectively stabilized, clinical experience suggests that 14 days is a reasonable
compromise and yields good results (8). The stent is removed by means of direct
laryngoscopy, and the operative result is assessed. Granulation tissue can be removed
with conservative use of a carbon dioxide laser. The need for additional endoscopic
manipulation is determined with serial fiberoptic laryngeal examinations. Decannulation
is best deferred until the patient can tolerate prolonged plugging of the tracheotomy tube.
Cricotracheal Separation
In the management of cricotracheal separation, several factors unique to this injury must
be considered. These include a precarious airway, loss of cricoid support, high risk of
injury to the recurrent laryngeal nerve, and late development of subglottic stenosis. When
a patient sustains lower cervical trauma, this injury must be considered and recognized so
that the tenuous airway can be preserved. This injury often is associated with
asphyxiation at the time of trauma. The airway is best controlled by means of
tracheotomy with the patient under local anesthesia. When this is impossible,
tracheotomy is performed after careful passage of a ventilating bronchoscope.
If the cricoid cartilage is intact, the mucous membrane is repaired directly with
absorbable suture. To distribute the tension on the wound away from the cricotracheal
anastomosis, nonabsorbable sutures are placed from the superior aspect of the cricoid
cartilage to the inferior aspect of the second tracheal ring. If the cricoid is fractured, the
effectiveness of repair is limited by the stability of the cricoid cartilage after internal
fixation. Reconstitution of the severely injured cricoid cartilage, with the assistance of
internal fixation and stenting, is preferable to extensive resection of the cricoid and
thyrotracheal anastomosis.
Severed Recurrent Laryngeal Nerve
Management of a severed recurrent laryngeal nerve continues to be a surgical dilemma.
Even with careful microscopic repair of the transected nerve, vocal fold mobility is not
regained owing to the mixture of abductor and adductor fibers in the nerve (20). Nerve
regeneration can prevent muscle atrophy, however, and help maintain some strength of
voice. Acute anastomosis of the phrenic nerve to the distal stump of the recurrent
laryngeal nerve and direct implantation of the phrenic nerve into the posterior
cricoarytenoid muscle have not proved more efficacious than simple anastomosis of the
severed nerve (21). Therefore it appears that the best acute-phase management is
immediate reapproximation of the nerve under an operating microscope.
COMPLICATIONS
Early recognition of laryngeal injuries and the application of consistent management
principles have decreased the morbidity and mortality from laryngeal trauma (Table
63.4). Success is measured in terms of restoration of the voice and the airway. Among
patients with edema, hematoma, or minor lacerations, excellent recovery of both voice
and airway usually can be achieved without surgery or with minimal surgical
intervention, such as tracheotomy or endoscopy. With severe lacerations and
cartilaginous fractures, good results can be achieved with early primary repair of
lacerations and internal fixation of fractures. In a series of 139 patients with laryngeal
trauma treated this way at the University of Texas Southwestern Medical Center at
Dallas, only two patients were left with a poor airway, as defined by the inability to
decannulate (Table 63.5). Time to decannulation among patients undergoing tracheotomy
and exploration ranged from 14 to 35 days. Patients with stents (usually reserved for
severe injuries) needed 35 to 100 days to decannulation (11). All but 13 of the 115
patients who could be evaluated achieved a good voice; the 13 were classified as having a
fair voice (22). Similar results have been obtained by other investigators who use these
management principles in the early primary management of laryngeal trauma (8,23).

TABLE 63.4. COMPLICATIONS LARYNGEAL
TRAUMA
a




TABLE 63.5. VOICE AND AIRWAY RESULTS



The most common problem in the immediately postoperative period is development of
granulation tissue, which most often happens in the presence of bare cartilage. This
problem often is the precursor to fibrosis and stenosis. Many techniques have been used
in attempts to arrest formation of granulation tissue, including the use of systemic and
intralesional corticosteroids, long-term splinting, and low-dose irradiation, but these
methods have had little success. Probably the most effective technique is to minimize the
initial formation of granulation tissue by attempting to cover all exposed cartilage
meticulously in primary closure of laryngeal lacerations. Using intraluminal stents only in
highly selected cases, as described earlier, and keeping the stents in place for the
minimum amount of time needed decreases the amount of granulation tissue that forms.
Despite strict adherence to proper principles of management of laryngeal trauma, fibrosis
and stenosis can occur. Therapeutic measures depend to some extent on the level of
stenosis. Supraglottic stenosis often can be corrected with simple excision of the scar
tissue and local advancement flaps for wound coverage. Sometimes this necessitates
removal of a large portion of the epiglottis or aryepiglottic fold. In rare instances,
supraglottic laryngectomy is needed. A keel or stent can be used as needed to maintain
the repair.
Rehabilitation from glottic stenosis depends on the extent of the lesion. Thin anterior
glottic webs can be simply lysed and a keel placed to prevent recurrence. Posterior glottic
webs or interarytenoid scarring can be excised during arytenoidectomy and resurfaced
with local mucosal advancement flaps. Extensive glottic stenosis often necessitates a
laryngeal fissure with direct excision of the stenotic area followed by placement of a
tissue graft with a stent to promote reepithelialization.
Subglottic stenosis continues to be difficult to manage, no matter what the cause. Less
extensive lesions can be managed with repeated dilation or conservative
noncircumferential laser excision of the scar tissue. More serious stenosis may necessitate
anterior or posterior cricoid splits with cartilage grafting to increase the size of the
subglottic lumen. Stenting usually is needed as are numerous endoscopic procedures to
excise granulation tissue after removal of the stent. Marked tracheal stenosis in a short
segment is managed by means of resecting the stenotic area and performing end-to-end
tracheal anastomosis (24). Lesions up to 4 cm in length can be resected with laryngeal
release techniques; however, the results with many of these techniques are disappointing,
and prevention of these complications continues to be the optimal treatment.
After blunt trauma, persistent immobility of the vocal fold may be caused by recurrent
laryngeal nerve injury or by cricoarytenoid joint fixation. Differentiating these causes is
essential in selecting the proper form of therapy, best accomplished by means of
observing the vocal fold for signs of movement with fiberoptic laryngoscopy or with
direct laryngoscopy under light anesthesia followed by direct palpation of the arytenoid
to assess its mobility. If the arytenoid cartilage is mobile, the vocal fold is observed for as
long as 1 year to await the possible spontaneous return of recurrent laryngeal nerve
function. If aspiration or dysphonia is severe, injecting the vocal fold with gelatin foam
paste can be a temporizing measure. Persistent paralysis resulting in an inadequate voice
can be rehabilitated with injection of polytetrafluoroethylene into the vocal fold or
thyroplasty-type vocal fold medialization procedures. In the case of unilateral fixation of
the arytenoid cartilage with adequate voice and airway, no treatment is needed. Bilateral
arytenoid fixation or recurrent laryngeal paralysis with a compromised airway often is
managed with arytenoidectomy and vocal fold lateralization, but the result is a weak
voice.
CONCLUSION
Although each instance of laryngeal trauma presents a unique therapeutic challenge,
using basic primary treatment principles greatly simplifies the management plan. Using
CT in some cases of laryngeal trauma obviates direct laryngoscopy and open exploration.
Tracheotomy rather than endotracheal intubation often is the best method for establishing
an alternative airway. Immediate open exploration for serious injuries allows primary
closure of all mucosal lacerations and preventing some long-term complications of
laryngeal trauma. Stenting is not needed when the cartilaginous skeleton is stable after
internal fixation and when mucosal coverage of the anterior commissure can be
reconstituted. Use of an early primary management protocol to manage laryngeal trauma
should predictably maintain successful laryngeal function.

HIGHLIGHTS
Computed tomography is the most useful radiologic
examination in the evaluation of laryngeal injury.
Management is determined by the findings at flexible
laryngoscopy and CT.
Hematoma, small lacerations, and edema are likely to resolve
with medical therapy alone.
Cartilage fractures, large lacerations with exposed cartilage,
disruption of the anterior commissure, and arytenoid injuries
necessitate surgical repair.
Tracheotomy is the preferred method for establishing an airway
with an injured larynx.
Mucosal repair is best accomplished immediately.
Primary mucosal coverage of exposed cartilage most effectively
prevents development of granulation tissue.
Grafts are used for coverage of exposed cartilage only when
primary mucosal coverage is impossible.
Stents are used only in the presence of anterior commissure
injuries or severely comminuted cartilage fractures.
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12. Schaefer SD. The treatment of acute external laryngeal injuries. Arch Otolaryngol Head Neck
Surg 1991;117:35.
13. Stanley RB, Cooper DS, Florman SH. Phonatory effects of thyroid cartilage fractures. Ann Otol
Rhinol Laryngol 1987;96:493.
14. Olson NR. Surgical treatment of acute blunt laryngeal injuries. Ann Otol Rhinol Laryngol
1978;87:716.
15. Harris HH, Tobin HA. Acute injuries of the larynx and trachea in 49 patients. Laryngoscope
1970;80:1376.
16. Downey WL, Owen RC, Ward PH. Traumatic laryngeal injury: its management and sequelae.
South Med J 1967;60:756.
17. Cohn AM, Larson DL. Laryngeal injury: a critical review. Arch Otolaryngol Head Neck Surg
1976;102:166.
18. Nahum AM. Immediate care of acute blunt laryngeal trauma. J Trauma 1969;92:112.
19. Thomas GK, Stevens MH. Stenting in experimental laryngeal injuries. Arch Otolaryngol Head
Neck Surg 1975;101:217.
20. Gordon JH, McCabe BF. The effect of accurate neurorrhaphy on reinnervation and return of
laryngeal function. Laryngoscope 1968;78:236.
21. Crumley RL. Phrenic nerve graft for bilateral vocal cord paralysis. Laryngoscope 1983;93:425.
22. Schaefer SD. The acute management of external laryngeal trauma: a 27 year experience. Arch
Otolaryngol Head Neck Surg 1992;118:598604.
23. Leopold DA. Laryngeal trauma. Arch Otolaryngol Head Neck Surg 1983;109:106.
24. Miller RH, Lipkin AF, McCollum CH, et al. Experience with tracheal resection for traumatic
tracheal stenosis. Otolaryngol Head Neck Surg 1986;94:444.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

64 MANAGEMENT OF SOFT-TISSUE TRAUMA
Head & Neck SurgeryOtolaryngology
64




MANAGEMENT OF SOFT-TISSUE TRAUMA
F. BRIAN GIBSON

F.B. Gibson: Department of Otolaryngology, Vanderbilt University, and Randolf ENT Associates,
Charlotte, North Carolina.


Etiology
Evaluation
Wound Management
Specific Types of Wounds
Scalp Wounds
Facial Nerve Injuries
Parotid Duct Injuries
Eyelid and Lacrimal System Injuries
Auricular Injuries
Nasal Injuries
Special Considerations in Children
Postoperative Care
Animal and Human Bites
Burns
Types of Burns
Inhalation Injury
Evaluation and Treatment
Special Types of Burns
Chapter References
Soft-tissue facial injuries are the cause of a huge number of emergency department visits.
These injuries can cause serious functional problems due to airway compromise or
hemorrhage or because of effects on structures such as the eyes or facial nerve branches.
The aesthetic effect of these wounds can be profound and is of great concern to both
patients and their families. Physicians who treat these patients must be technically skilled
in the repair and management of facial wounds. They must also establish rapport with the
patient and the family while building confidence for the continued care these patients
frequently need. Careful and skilled management is needed to minimize aesthetic
deformity and mitigate functional losses.
ETIOLOGY
The chief causes of facial soft-tissue injuries are motor vehicle accidents, violent acts,
work-related injuries, other accidental injuries, animal and human bites, and burns. About
50% to 70% of survivors of motor vehicle accident have facial injuries, despite laws in
many states requiring seat belt use (1). One report provides clear documentation of the
value of airbags and restraining devices in preventing facial fractures and lacerations (2).
Blunt trauma is frequently characteristic of injuries from altercations and athletic injuries.
Other common athletic injuries are lacerations, particularly of the eyelids and nose, facial
contusions, and auricular hematoma, especially among wrestlers. Work-related accidents
are less common than in the past but can manifest as simple lacerations, blast injuries,
burns, or penetrating trauma.
EVALUATION
When confronted with a trauma patient, a physician follows an orderly approach
addressing each problem according to priority: airway evaluation and protection, control
of hemorrhage, and management of shock, followed by management of serious
associated injuries and evaluation of facial trauma (Table 64.1). Airway treatment of
trauma patients is discussed in Chapter 58. Bleeding from facial wounds typically
manifests as oozing from the wound margins. If severe hemorrhage is found, it probably
arises from larger branches of the facial or superficial temporal arteries. These can be
controlled by means of direct pressure followed by ligation through the wound. During
urgent treatment of associated injuries such as chest or abdominal trauma, facial wounds
can be protected with saline-soaked gauze until more complete evaluation is possible.

TABLE 64.1. EMERGENCIES FACIAL SOFT-
TISSUE TRAUMA



Evaluation of facial trauma proceeds in a systematic manner. A careful examination is
conducted to find injuries to the facial skeleton, eyes, salivary structures, facial nerve,
and other soft-tissue components. Observation of the entire face and its subunits can
disclose asymmetries that suggest underlying fractures and reveal facial nerve injuries.
Palpation of the facial bones is the single most sensitive and reliable way to detect facial
fractures. Radiographic studies serve as adjuncts to this examination. Useful views
include the Waters and the Towne projections, anteroposterior, oblique, and
submentovertex views. Panoramic tomography and computed tomography (CT) also can
be helpful. Some injuries must be approached with suspicion of trauma to contiguous or
deeper structures. Deep lacerations to the cheek suggest injury to the facial nerve or
parotid duct. Medial eyelid injuries can be accompanied by damage to the canthal tendon
or the lacrimal apparatus. Periorbital injuries most commonly necessitate ophthalmologic
evaluation that includes visual acuity testing and examination with a slit lamp.
Documentation of the injuries with photographs and a complete description in the
medical record is essential.
WOUND MANAGEMENT
Soft-tissue trauma to the face ranges from superficial abrasions to massive tissue loss
associated with blast injuries. It includes contusions, lacerations, avulsion injuries, burns,
and cold injuries. Many facial injuries can be repaired in the emergency department, but
complex wounds, those associated with facial fractures, lacrimal, nerve, or ductal injury,
or those in small children frequently must be repaired with the patient under general
anesthesia. If other injuries necessitate urgent surgical intervention, the facial trauma can
often be repaired at the same time. When repair must be postponed, simple
reapproximation of the tissue, often with a few sutures, improves the result.
Before repair is begun, adequate anesthesia must be obtained to relieve discomfort and to
allow the surgeon freedom to proceed with tissue manipulation. Most facial wounds are
managed under local anesthesia, usually 0.5% to 1% lidocaine with 1:100,000
epinephrine, either through regional blocks of the trigeminal divisions or through direct
infiltration. Buffering the lidocaine solution with a small amount of bicarbonate to
achieve a 10:1 mixture and using small-gauge needles and slow rates of injection lessen
discomfort while anesthesia is obtained. Topical preparations such as the combinations of
tetracaine, epinephrine, and cocaine or tetracaine, adrenaline, and lidocaine can be
effective in the preparation of children for full anesthesia or to reduce the discomfort of
injection with anesthetic medications. Oral sedation with midazolam, 0.3 to 0.5 mg per
kilogram, has been proved to reduce anxiety among children (3).
After anesthesia is obtained, the skin surrounding the wound can be washed with an
antiseptic preparation such as povidone-iodine or chlorhexidine. The wound itself is not
exposed to these agents because they impair healing (4). Copious saline irrigation with a
bulb syringe, intravenous catheter on a syringe, or pulsatile irrigator removes foreign
material and bacteria. All dirt, glass, and other foreign material must be removed for
primary repair to avoid traumatic tattoos and decrease the risk of infection or granuloma
formation. If irrigation does not remove all debris, the wound can be scrubbed with a
brush, but care must be taken to avoid further tissue injury from too-vigorous scrubbing.
Solvents such as ether or acetone can be used to dissolve contaminating tar and other
petroleum products. Small foreign bodies are extracted with a no. 11 scalpel blade, but
wound exploration may be needed to remove larger pieces.
Prophylactic antibiotics are not essential for clean facial wounds, but depending on the
degree of contamination, many surgeons prescribe several days' coverage with oral
cephalosporin or a similar agent. Several factors contribute to increased microbial
contamination; the most important of these is the time elapsed since the injury occurred.
Skin flora such as streptococci or staphylococci usually are found in facial wounds.
Mucosal or through-and-through lacerations into the oropharynx expose the wound to
mixed flora. Bite injuries often carry animal or human saliva deep into the tissues. The
presence of dirt and other foreign materials increases the risk of infection. Inadequate
perfusion and wound desiccation can retard antibiotic penetration into the wound.
Tetanus prophylaxis is administered to patients with contaminated wounds if they have
not been immunized in the last 5 years.
Specific Types of Wounds
Abrasions
Abrasions are a special class of superficial wound in which contact with a rough surface
denudes the skin. These wounds are frequently found to have embedded dirt and debris
and must be cleaned thoroughly. They can then be covered with topical antibacterial
ointment and a dressing. Maintaining a moist surface with the ointment enhances
reepithelialization. Pigmentation abnormalities can develop during healing but usually are
temporary.
Contusions
Contusions are bruising injuries caused by blunt trauma to facial capillaries and small
vessels. In almost all cases, they necessitate no specific treatment and usually resolve if
the head is kept elevated above the level of the heart and ice is applied. More forceful
blows can cause diffuse or localized soft-tissue hematoma. Diffuse hematomas gradually
resolve without treatment. If localized hematomas are large, they can cause pressure
necrosis of subcutaneous tissues, and the result is scar contracture. To prevent these
complications, large hematomas can be drained through small, cosmetically acceptable
incisions during the first 7 to 10 days after injury. Hematomas can be aspirated
successfully after 10 to 14 days.
Lacerations
Lacerations can be linear, tangential, stellate, or combined with avulsion. Simple
lacerations are best managed with minimal dbridement and primary closure in the
emergency department. Facial wounds usually necessitate little dbridement because the
excellent blood supply allows greater tissue survival than in other parts of the body and
provides much greater resistance to infection (Fig. 64.1). For this reason, facial wounds
can be closed primarily up to 48 or even 72 hours after injury. Atraumatic technique with
fine instruments and fine suture material is vital. Facial lacerations are closed in layers
with enough sutures to achieve a tension-free closure. The surgeon avoids handling the
skin edges with a forceps, because doing so crushes the microvasculature and causes
necrosis. Skin hooks are preferred because they allow atraumatic tissue manipulation.
Judicious undermining of the wound margin lessens tension across the suture line and
facilitates placement of deep sutures. Care is taken, however, not to compromise the
viability of partially avulsed flaps or to distort contiguous structures with excessive
undermining.

FIGURE 64.1. Dbridement and undermining of
lacerations. A: Minimal dbridement preserves vital
tissue. Beveling the wound edge outward promotes
eversion during closure. B: Undermining reduces tension
and eases placement of deep sutures.



The choice of suture material is based on the nature of the wound and the surgeon's
preference (5). Deep sutures usually are of absorbable material such as polyglactin 910 or
polydioxanone to reduce the risk of future foreign-body reactions. These sutures are
placed in an inverted manner with enough stitches to take all tension off the wound
edges. The aim of suture techniques in facial injuries is to achieve accurate tissue
approximation without strangulation or excessive tension (Fig. 64.2). The superficial skin
layers can be closed in a number of different ways (Fig. 64.3). Cutaneous sutures are used
only to reapproximate the epithelium while the skin edges are everted. Eversion allows
wound contraction without formation of a depressed scar. Monofilament nonabsorbable
suture material or fast-dissolving catgut is commonly used for the epidermal closure.

FIGURE 64.2. Suturing principles for facial wounds. A:
Inverted deep sutures reapproximate the wound edges,
eliminate dead space, and juxtapose similar tissue layers.
B: Eversion of surface by well-placed sutures.



FIGURE 64.3. Suturing techniques. A: Simple
interrupted. B: Subcuticular running. C: Vertical
mattress. D: Simple running. E: Running locked.



Tissue adhesives have become popular in recent years because of their greater
convenience, patient comfort, and speed compared with suturing. A study comparing use
of octylcyanoacrylate tissue adhesive with suturing concluded that the adhesive was
equally effective, provided equivalent cosmesis, and was much faster (6). In another
study, investigators concluded that a superior cosmetic result was achieved with N-butyl-
2-cyanoacrylate glue as opposed to suturing of facial lacerations oriented against the
Langer lines (7).
Complex lacerations include stellate, irregular, and trapdoor wounds. Small stellate
wounds often can be excised and converted into simple lacerations, which are then closed
primarily (Fig. 64.4). Larger, more complex wounds must be closed meticulously; scar
revision can be performed later. Trapdoor lacerations are caused by tangential partial
avulsion injury that leaves a U-shaped flap of tissue on a thin pedicle. If this flap is small,
it can be excised and the surrounding tissue closed primarily. Larger flaps must be
replaced and closed; care is taken to avoid a pincushion deformity (Fig. 64.5). This
deformity arises when tissue edema and wound contraction raise the central part of the
flap. To prevent this, the thin beveled portion of the flap is dbrided to a straight edge and
surrounding tissue undermined so that corresponding levels in the tissue can be
reapproximated.

FIGURE 69.4. Management of small stellate wounds. A:
Small stellate laceration. B: Excision of the wound along
relaxed skin tension lines produces a fusiform defect. C:
Primary closure of the wound.



FIGURE 64.5. Avulsion injury that has caused trapdoor
laceration. A: The wound has a U-shaped flap. B:
Pincushion deformity after improperly performed primary
closure. C: Proper reapproximation of similar tissue
layers to help prevent pincushion deformity.



Avulsion
Avulsion injuries cause full-thickness tissue loss and can cause severe cosmetic
deformity. Small partially avulsed defects with a viable pedicle can be repaired primarily.
The defect also can be excised and the wound converted into a laceration-type defect that
is closed primarily in a more aesthetic manner. Larger full-thickness defects may
necessitate a graft or local flap. Skin grafts may be preferable during primary wound
management; after the defect begins to heal, the graft can be excised, if desired, and
replaced with a local flap. An alternative is to leave the wound open to heal by secondary
intention. Massive tissue loss can necessitate open management to allow granulation to
begin, particularly if there is exposed bone, before placement of an appropriate graft.
Burring of the cortex to expose the medullary compartment encourages granulation. Both
partial-thickness and full-thickness skin grafts can be used to repair facial injuries.
Partial-thickness grafts have the disadvantages of contracture and poor color match in
most cases but survive much more readily than full-thickness grafts. Full-thickness grafts
have superior color and texture characteristics and do not undergo marked contracture.
Scalp Wounds
Lacerations and avulsions of the scalp are a special class of wounds because of the
anatomic peculiarities of this area. The scalp is made up of five layers (Fig. 64.6),
including a thick dermal layer (3 to 8 mm deep) and the galea, a fibrous layer continuous
with the frontal muscle anteriorly and the temporoparietal fascia laterally. The rich blood
supply to the scalp arises in the galea before passing into the subcutaneous tissues, where
the large plexus of vessels contributes to the profuse bleeding that often occurs from
fairly small wounds. Lacerations of the scalp are treated by means of undermining the
subaponeurotic plane above the pericranium and performing a layered closure.

FIGURE 64.6. Five layers of the scalp: A, skin; B,
subcutaneous tissue; C, muscle and aponeurosis; D, loose
connective tissue; E, pericranium.



When tissue loss has occurred, the relative inelasticity of the scalp makes advancing
tissue for closure difficult. Primary closure often can be performed for defects up to 3 cm
in size by means of wide undermining in the loose subgaleal plane. Dividing the galea
with relaxing incisions 12 to 15 mm apart provides about 3 mm of additional mobility for
each incision made. If the defect is too large to close primarily and the pericranium is
intact, a split-thickness skin graft can be placed with good results. Secondary tissue
expansion and flap reconstruction can be used to resurface as much as 50% of the scalp.
If the pericranium is not intact but the surrounding scalp is viable, rotation or other scalp
flaps can be used to fill the deficit. The donor site defect is closed either primarily or with
a skin graft that can later be removed during secondary reconstruction. Local flaps,
however, are not useful for defects larger than 5 cm in greatest dimension. These defects
must commonly be managed with skin grafts, distant pedicle flaps, or free-tissue transfer,
such as a latissimus dorsi flap. Total or near-total avulsions are best managed by means
of microvascular reanastomosis and replantation if scalp tissue is available. If not, free-
tissue transfer is the best option.
Facial Nerve Injuries
Facial nerve injuries can occur with penetrating or laceration wounds to the lateral face,
facial fractures, and avulsion injuries. Nonpenetrating injuries also can cause facial palsy
but usually are managed expectantly (8). Injuries anterior to a vertical line through the
lateral canthus rarely cause permanent problems because of anastomotic branching and
reinnervation from other peripheral branches. Injuries posterior to this line or those
involving major branches necessitate repair. Distal injuries to the frontal and marginal
mandibular nerves, which are solitary terminal branches, often lead to poor recovery of
function, and the physician needs to consider repairing them.
Facial nerve injuries are repaired during initial wound management if possible, and
wounds associated with paralysis are explored to locate the cut branches. Because
excitability is lost after about 72 hours, repair is much easier during this time frame. The
distal branches can be found with a nerve stimulator; the proximal branches often can be
found by means of tracing a buccal branch back to the main trunk. If this is not possible,
the nerve can be found at its exit from the stylomastoid foramen and traced through the
parotid gland. If primary repair cannot be done, the nerve branches are tagged with
permanent sutures or clips for later reanastomosis. Reapproximation is performed under
an operating microscope with 8-0 to 10-0 monofilament suture material. Epineural repair
often is recommended, because perineural or fascicular repair has not produced greater
functional recovery. Some authors have expressed concern that epineurium can
proliferate at the site of repair and obstruct axonal regeneration. They recommend
perineural repair after the distal 5 mm of epineurium is trimmed (8). If there is not
enough residual nerve tissue to provide a tension-free anastomosis, a cable graft of
greater auricular or other peripheral nerve can be used. A greater auricular graft can
provide up to 7 cm of nerve tissue; sural grafts can be as long as 30 cm. Rerouting the
nerve within the mastoid process can provide 1 cm of additional length if needed.
Parotid Duct Injuries
Vertical lacerations below the anterior border of the masseter muscle are likely to injure
the parotid duct. This duct is on a line drawn from the tragus to the midportion of the
upper lip. The buccal branch of the facial nerve travels alongside the duct and often is
damaged as well. Examination of patients with injuries to both structures discloses
paralysis of the upper lip levators and saliva in the wound. These injuries are best
managed by means of repair of the nerve as described previously and stent repair of the
duct.
A soft polymeric silicone or polyethylene 22-gauge catheter is introduced into the papilla
of the Stensen duct and passed retrograde. The cut proximal end of the duct is identified,
either by its appearance or by the flow of saliva produced by pressure on the parotid
gland. The catheter is passed to the gland through the proximal duct. The duct is repaired
over the stent with interrupted 6-0 or 7-0 monofilament suture under an operating
microscope (Fig. 64.7). The catheter can be secured to the buccal mucosa with a suture
for 10 to 14 days. Less desirable management options include tying off the duct, which
results in gland atrophy after a period of parotid swelling, pain, and occasionally
infection. The duct can be rerouted more proximally into the oral cavity, but the
procedure is technically difficult, and keeping the stoma open is frequently a problem.
Complications of parotid injuries include sialocele and fistula. Management of these
problems usually is nonsurgical and includes pressure dressings, anticholinergic
medications, and aspiration of cysts as needed. Antibiotics can be given if signs of
infection develop. Parenteral nutrition sometimes is needed to decrease salivary flow
enough to allow healing. These sialoceles and fistulae usually resolve within 1 to 3
weeks.

FIGURE 64.7. Repair of parotid duct (after Manson).



Eyelid and Lacrimal System Injuries
The eyelid requires special attention to reconstitute its protective and aesthetic functions.
Because eyelid injuries can indicate underlying globe injury, the eyes are thoroughly
evaluated for abrasions or lacerations of the cornea, disruption of the globe, and
hyphema. Consultation with an ophthalmologist is mandatory for patients with suspected
ocular injuries. These patients need testing of visual acuity, assessment of extraocular
motion, exclusion of diplopia, and a funduscopic examination; these assessments are
done before treatment. Several important anatomic points must be remembered. The
orbicularis muscle in both upper and lower eyelids, particularly its pretarsal segment, is
primarily responsible for blinking and must be preserved or repaired if injured. Two
muscles are active in upper lid elevation, the levator palpebrae superioris, which is
innervated by the oculomotor nerve, and the Mller's muscle, which is under sympathetic
control.
Simple lacerations of the eyelid skin are repaired with 5-0 or 6-0 monofilament sutures,
which usually are removed about 5 days after repair. Through-and-through lacerations of
the lid are closed in two or three layers. If the conjunctival portion is not too severe, it can
be left open; otherwise it is closed with a 5-0 or 6-0 buried absorbable suture such as
chromic catgut. The tarsus and the orbicularis muscle are reapproximated with absorbable
suture material such as 5-0 polyglycolic acid. The gray line at the lash margin is repaired
first then the anterior and posterior lid margins with 5-0 or 6-0 monofilament material
(Fig. 64.8). Injuries to the orbicularis or levator muscles are suspected in these cases and,
if found, must be repaired with absorbable sutures.

FIGURE 64.8. Repair of eyelid lacerations. A:
Reapproximation of gray line. B: Conjunctival repair
with inverted absorbable sutures. C: Orbicularis
reapproximation. D: Skin closure.



Canalicular injuries also are suspected in medial eyelid lacerations, and the ducts are
probed or a Jones test is done. If the canaliculi are injured, exploration is performed
under magnification, and silicone stents are passed into the nasolacrimal ducts and out
into the nose. These are left in place for several weeks until healing has occurred (Fig.
64.9). The canaliculi can be repaired with 10-0 suture material under an operating
microscope once the stents are passed. Medial canthal injuries are repaired with
permanent suture to avoid traumatic telecanthus. If there is not enough proximal tendon
left for repair, transnasal wiring can reestablish continuity of the tendon.

FIGURE 64.9. Approach to canalicular injuries. A:
Probing the canaliculus to test patency. B: Stent
placement.



Injuries that cause tissue loss from the eyelid can be difficult to repair. Loss of up to one-
fourth of the lid can be repaired primarily, but if more tissue is lost, primary repair causes
entropion. Closure can sometimes be effected by means of lateral canthotomy, which
provides an additional 5 to 10 mm of length. If lateral canthotomy is not sufficient, grafts
must be placed and can frequently be obtained from the contralateral eyelids or from the
supraclavicular or postauricular areas. Reconstruction of full-thickness loss is quite
complex and can involve septal cartilage grafts, mucosa, and skin grafts. Care must be
taken with eyebrow repair, because reconstruction is quite difficult. To avoid
irregularities in reapproximating the hairline, the eyebrows never are shaved during
wound closure; also, the hair may not regrow. Dbridement is done parallel to the hair
shafts to avoid injuring the hair follicles.
Auricular Injuries
Injuries to the complex cartilaginous structure of the ear are a challenge because skillful
initial repair can eliminate the need for potentially difficult secondary reconstruction. To
an even greater extent than with other structures, the tissues that make up the pinna are
difficult to replace and must be preserved if at all possible. Auricular lacerations are
repaired with absorbable sutures through perichondrium and fine sutures for skin closure.
Sutures are not placed through the cartilage because they increase the risk of chondritis.
Most auricular lacerations are closed primarily, except for human bites, which are
extensively contaminated and can benefit from 3 to 4 days of open treatment before
delayed closure. Notching of the helix can occur as wound contraction occurs, but this
can be revised with a Z-plasty.
Avulsion of the skin with exposure of intact perichondrium can be managed with full-
thickness skin grafts. Denuded areas of cartilage require wedge excision, burial in a
pocket, or coverage with local pedicle flaps. Cutaneous blood flow to the ear is excellent,
so partial avulsions survive on a small pedicle. A 1-mm to 2-mm pedicle often ensures
successful replantation of the partially avulsed auricle. Full-thickness defects up to 5 mm
can be closed primarily. If it is available, the amputated segment often can be replaced as
a composite graft. There is a good chance of success if none of the graft is more than 1
cm from a blood supply. If the avulsed fragment is unusable, a composite graft from the
other ear restores symmetry.
Large-segment avulsion can be managed in a number of ways. One technique is
replantation of the avulsed ear after removal of the medial skin and fenestration of the
cartilage at 1-cm intervals. A mastoid skin flap is developed and sutured to the medial
surface of the ear to provide nourishment (Fig. 64.10). After 2 to 3 months, the flap can
be taken down and the auricle covered with a skin graft. The pocket principle is another
approach. The auricular epithelium is removed by means of dermabrasion followed by
replantation of the segment. The replanted ear is covered in a postauricular pocket for 10
to 14 days, and the lateral surface is released. The final stage is release of the medial
surface 1 week later. The epithelium regenerates from the remaining dermis. The
temporoparietal flap used by Brent and others for reconstruction of congenital atresia can
aid in replanting a severed ear. Although this flap is quite thin and can be covered with a
skin graft, distortion of the finer topographic features of the auricle is inevitable.

FIGURE 64.10. Approach to auricular avulsions. A: The
Baudet technique includes reattachment of the segment
after fenestration of the cartilage. B: Pocket principle
with dermabrasion of the epithelium and placement of the
segment into a postauricular pocket.



When suitable vessels are present, microvascular techniques provide the best long-term
cosmetic results for the amputated auricle. This approach avoids the distortion of the
auricle common in other techniques; however, failure of replantation usually results in
total loss of the auricular cartilage. Reanastomosis can be performed with small branches
from the superficial temporal and posterior auricular vessels. Heparin, dextran, and other
agents are used postoperatively to promote blood flow and retard thrombosis (9).
Hyperbaric oxygen improves survival of replanted facial tissues. The increased partial
pressure of oxygen delivered during hyperbaric therapy allows a greater amount of
oxygen to be transported in solution in the blood (up to 6 mg/dL). Hyperbaric therapy
increases the diffusion distance from intact capillaries because of a greater concentration
gradient. The rate of neovascularization is increased with hyperbaric oxygenation, and
edema is decreased.
Auricular hematoma is characteristic of contact sports such as boxing and amateur
wrestling. The injury occurs when shearing force is applied to the anterior perichondrium
and skin, causing microvascular disruption (Fig. 64.11). Blood accumulates in the
subperichondrial space. Treatment consists of either needle aspiration or incision and
drainage. After the blood is evacuated, compression dressings of cotton or dental rolls
soaked in saline solution or mineral oil and shaped into a conforming mass are applied to
prevent reaccumulation. The sequela of untreated auricular hematoma is the thickened,
fibrotic cauliflower ear.

FIGURE 64.11. Auricular hematoma. A: Blood usually
accumulates in the anterior perichondrial space. B:
Evacuation of the hematoma is followed by placement of
a bolster dressing with through-and-through sutures.



Nasal Injuries
Injuries to the nose are a special situation because of the complex anatomic structures
affected and the need to restore near-perfect symmetry to avoid a cosmetically poor
result. Through-and-through lacerations are repaired in the same way as injuries that
penetrate into the mouth. Each layer is closed in turn. When tissue loss has occurred,
concern focuses on three major componentsintranasal lining or mucosa, cartilaginous
and bony framework, and external cover or skin losses. Each of these must be replaced to
return the nose to good functional and aesthetic condition.
Tissue loss of less than 5 mm
2
usually can be repaired primarily by means of mobilizing
surrounding tissues and performing a layered closure. Complete amputation is managed
with microvascular replantation whenever possible. For other defects, a number of
techniques are possible. If the avulsed segment is available and less than 1 cm in area, it
can be replaced and sutured back into position with a good chance of full survival. Losses
of skin greater than 5 mm
2
are best managed with local flaps or skin grafts. Rhomboid,
bilobed, nasolabial, and other flaps all play a role in nasal surface reconstruction. Defects
greater than 1.5 cm
2
usually are managed with tissue derived from surrounding areas such
as a forehead or nasolabial flap. The nose usually does not supply enough excess skin to
cover such a defect and allow primary closure of the donor site. Composite defects can be
repaired with a combination of local flaps, cartilage grafts, and skin-mucosa grafts.
Special Considerations in Children
Physicians treating injured children face additional challenges. The history of the
accident can be difficult to obtain, so a more vigorous search for occult injuries is needed.
Airway and circulatory management is critical in the care of children because the
smaller-caliber airway and lower circulating blood volume make children more
vulnerable to airway obstruction and shock. Because children are more likely than adults
to have hypertrophic scars, reducing tension on wound margins is even more important.
Suture removal, often a problem for children, can be avoided by means of placement of
absorbable 6-0 catgut or subcuticular sutures with reinforcing adhesive wound closure
tape.
Postoperative Care
Once they are closed, all wounds are dressed with a layer of antibiotic ointment and kept
meticulously clean. Effective topical antibiotic preparations include bacitracin ointment
and bacitracin-polymyxin B and mupirocin. All of these agents reduce the risk of wound
infection and provide a moist environment that enhances healing. Some patients have
superinfection with Candida organisms, which must be recognized and managed
appropriately. Neomycin-containing agents usually are avoided because of the relatively
high incidence of chemosensitivity. After initial treatment, the wound is cleaned three to
four times a day and additional ointment applied. Nonadherent occlusive dressings such
as perforated nonadherent dressing, semipermeable film dressing, hydrocolloid
semipermeable dressing, or a number of other products can be used and have been shown
to speed healing and decrease the risk of infection. Sutures can be removed beginning the
third or fourth day and sterile adhesive strips applied to the wound. The surgeon must
watch for development of infection, early hypertrophic scarring, or other complications
(Table 64.2).

TABLE 64.2. COMPLICATIONS FACIAL
SOFT-TISSUE TRAUMA



Animal and Human Bites
Most animal bite injuries occur among children younger than 10 years. The annual
incidence in the United States is about 150 cases per 100,000 for children younger than 4
years. It decreases to 60 cases per 100,000 for 10- to 14-year-olds. The most common
animal bites are from dogs (86%), followed by cats (8%), rodents (4%), and wild animals
(1%). Bites can take the form of lacerations, avulsions, or puncture wounds. About one
half of patients have more than one bite. The most common injury is a crescent-shaped
laceration of the lateral face, lip, or nose. The factors contributing to animal bites are
difficult to determine, but in one study it was found that only 6% of injuries occurred
when a dog was being teased or abused (10). Mongrels and strays account for 28% of dog
bites, and German shepherds are the most commonly involved purebred dogs (18%).
Male dogs and younger dogs have been found to bite more frequently than female and
older dogs. Many bite injuries occur in the owner's home or yard when the animal bites
owing to its territorial instincts.
Management of relatively recent wounds consists of thorough cleansing and antisepsis,
minimal dbridement of contaminated tissue, and primary closure. Prophylactic
antibiotics are effective against both gram-negative and gram-positive organisms.
Tetanus prophylaxis is brought up to date for patients who need a booster. Rabies is the
most feared sequela of a bite. Only one or two cases occur in the United States each year,
most commonly from wild animal bites. Skunks, bats, foxes, and raccoons are the main
sources of human rabies. If the animal cannot be captured and if rabies is endemic for the
species, rabies prophylaxis with hyperimmune globulin and vaccination is instituted.
Appropriate management of human bites is controversial. Because these injuries are
contaminated by a large and varied number of organisms, some surgeons advocate
delayed primary or secondary closure. Others propose that with adequate antibacterial
prophylaxis, early primary closure yields superior aesthetic and functional results.
BURNS
Types of Burns
Although the head and neck occupy only 9% of the total body surface area (TBSA), they
are the most common sites of thermal injury. The most common causes of head and neck
burns are hot water, flames, industrial accidents, and flammable liquids. Electrical
injuries and frostbite also can affect the head and neck. Burn injuries can be divided into
full thickness and partial thickness. First-degree burns are superficial and involve the
epidermis, causing pain, mild redness, and little tissue damage. They typically heal within
5 to 10 days. Second-degree or deep partial-thickness burns penetrate into the dermis and
damage the adnexa and nerve endings. They cause severe pain and blistering, but they
retain the possibility of epithelial regeneration. Healing can take 10 to 30 days, depending
on the depth of dermal injury. Full-thickness or third-degree burns cause irreversible
destruction of the deep dermis. Epithelium does not regenerate, and the nerve endings are
destroyed. These wounds can be divided into three areasa central zone of coagulation,
where thermal coagulation and microvascular occlusion are complete; a surrounding zone
of stasis, where vascular sludging is caused by accumulation of slowly flowing blood
elements and waste products; and a peripheral zone of hyperemia (11,12).
Inhalation Injury
Injury to the airway, which occurs among 25% to 35% of patients admitted to large burn
centers, is the leading cause of death among burn patients (13). The incidence of
inhalation injury varies from less than 10% among patients with a 5% TBSA burn to
more than 80% among patients with a burn covering more than 75% TBSA. Serious
inhalation injury can increase the mortality rate as much as 20%.
If a burn occurs in a confined space such as an automobile or is caused by steam or other
superheated gases, inhalation injury is likely. Signs of inhalation injury include singeing
of the nasal hairs, facial burns, soot in the sputum, hoarseness, tachypnea, wheezing, or
rhonchi. The presence of burns on the head and neck is not a prerequisite for inhalation
injury; three fourths of patients with airway injuries do not have associated facial burns.
Airway injuries can occur in several different ways. Flames or hot gases can injure the
upper airway directly, causing edema and obstruction within 8 to 24 hours after injury.
Direct thermal injury to the infralaryngeal airway is rare because the glottis closes
reflexively to protect the distal airway. Steam, however, can cause injury down to the
bronchioles because of its high heat-carrying capacity (4,000 times that of air). Toxic
compounds in smoke can include phosgene, ammonia, sulfur dioxide, and chlorine from
plastics and various oxides and aldehydes from burning wood. These compounds directly
injure airway epithelial cells and cause an intense inflammatory response with substantial
edema. Respiratory distress, which may not develop until 12 to 48 hours after the injury,
is caused by chemical tracheobronchitis. Sloughing of the mucosa and failure of ciliary
function allow epithelial debris to accumulate and cause atelectasis and hypoventilation.
Carbon monoxide toxicity is the other major cause of airway injury. This molecule has an
affinity for hemoglobin 200 times higher than does oxygen and causes tissue hypoxia by
changing the oxygen-hemoglobin dissociation curve. Blood carboxyhemoglobin levels
greater than 1.5% among nonsmokers and 5% among smokers suggest severe carbon
monoxide exposure. Treatment with 100% oxygen decreases the half-life of
carboxyhemoglobin from 4 hours to 30 minutes and ameliorates hypoxia.
Evaluation and Treatment
Initial assessment and treatment of a patient with head and neck burns include control of
the airway and circulation and determination of the extent and depth of the burn injury.
Indications for intubation include obtundation, edema, and mucosal injury causing
mechanical obstruction of the airway, inhalation injury, and severe cervicofacial burns.
About 60% of patients with both burns and inhalation injury need intubation; only 12% to
15% with inhalation injury alone need airway management (13). High-frequency
ventilation provides adequate oxygenation with a lower fraction of inspired oxygen and
airway pressures and markedly decreases atelectasis. Early tracheotomy results in an
increased risk of pulmonary sepsis caused by contamination from wound flora. Most
treatment centers reserve tracheotomy for patients who cannot be intubated and those
who have needed intubation for more than 14 to 21 days. Additional airway therapy
includes bronchodilators, but steroids are avoided because of the increased mortality risk
among patients with airway injuries and cutaneous burns.
Evaluation of patients believed to have inhalation injury includes chest radiographs,
arterial blood gas sampling, and direct examination of the airway with a fiberoptic
bronchoscope. Radiographic findings often are normal immediately after the burn injury
but serve as a baseline for serial examinations. Bronchoscopy allows visualization of
pharyngeal or laryngeal edema, erythema, or charring. The lower airways can be
visualized, and soot, inspissated mucus, or debris can be removed by means of lavage.
Pulmonary function tests and xenon lung scanning also can be useful.
Management of burn injuries includes fluid resuscitation following the Parkland Hospital
protocol or another formula, tetanus prophylaxis, and vigilant wound care and
observation. Meticulous wound care must be performed to prevent infection, contracture,
and other devastating sequelae of burn injuries. Sepsis is still a major cause of death
among patients with severe burns. Antibiotics often are given prophylactically at the time
of eschar excision, when autografts are placed, and when evidence of infection appears.
Routine use of systemic antibiotics is avoided because of the tendency for development
of bacterial resistance and selection of virulent organisms. Penetration of circulating
antibiotics into the more central portions of the burn wound often is poor. For these
reasons, topical antibiotic ointments such as mafenide acetate, bacitracin, and
sulfadiazine silver are more commonly used for head and neck burns.
Management of head and neck burns begins with thorough cleaning and dbridement of
necrotic tissue. Early excision of burned areas and autografting are gaining favor. Ten to
14 days after injury, burned areas that do not show signs of healing are excised. A two-
stage process is followed: Tangential excision of the burn eschar allows preservation of
the maximum amount of viable tissue. One or two days later, the patient is returned to the
operating room for placement of split-skin grafts and a pressure splint. This approach
reduces the scarring caused by development of granulation tissue. In planning grafts to
the face, the concept of aesthetic units is used as a guide to optimize the cosmetic results
(Fig. 64.12). Grafts cover an entire aesthetic unit to minimize the conspicuousness of
scarring. Thick grafts (0.015 to 0.035 inch [0.38 to 0.89 mm]) provide superior texture
and reduce contracture. If a tracheotomy is planned, early excision and grafting of the
neck allow placement of the tube through healed autograft.

FIGURE 64.12. Aesthetic units of the face.



Treatment must also include vigorous physical and occupational therapy. Scar
contracture can be minimized with daily repetition of active and passive range-of-motion
exercises, early return to self-care, and use of conforming splints when indicated.
Particular attention must be directed at preserving neck and jaw motion. Hypertrophic
scarring is reduced by means of continuous pressure therapy that begins as soon as the
grafts have healed and continues for 12 to 18 months. Pressure can be applied with elastic
garments or clear safety masks, custom-fitted to each patient.
Special Types of Burns
Ears
Certain areas of the head and neck have unique therapeutic considerations. The ears are
covered with thin skin and are injured in more than 90% of head and neck burns. They
must be treated gently with local cleaning and application of topical antibiotics. No
pressure is applied to the ears, and pillows are not used. The ears are prone to the
development of suppurative chondritis, a complication that can cause loss of or severe
deformity of the pinna. Signs of suppurative chondritis include redness, swelling, and
deep pain. Suppurative chondritis is managed with incision, drainage, and dbridement.
Prevention centers on vigorous local care, which can include antibiotic iontophoresis and
early dbridement and grafting. Exposed cartilage may have to be resected, or it can be
covered with a postauricular flap. If the cutaneous covering of the ear is nonviable, the
ear can be buried in a postauricular pocket. An alternative is to excise the entire ear,
deepithelialize it, and place it in an abdominal pocket for later reconstruction.
Mouth
Burns of the mouth often are electrical in nature and occur when children bite appliance
power cords. The initial appearance of these burns is deceptive. There usually is more
tissue damage than is immediately apparent. Opinions are mixed on the virtues of
conservative treatment versus early excision and grafting. Conservative treatment, which
allows eschar separation, can be complicated by hemorrhage from the labial arteries.
Surgical treatment can be delayed 10 to 14 days to allow demarcation of the involved
area. The long-term complication of these injuries is contracture resulting in microstomia.
This scarring can be prevented by means of fitting the patient with an appliance, typically
during the third week after injury. Use of this appliance often eliminates the need for
surgical treatment.
Eyelids
As with lacerations, burn injuries to the eyelids lead the physician to suspect underlying
ocular injury, and a thorough ophthalmologic examination is needed. During healing, the
corneas must be protected and prevented from drying. Moisture chambers, lubricants, and
antibiotics all have a role in therapy for eyelid burns. These burns can heal spontaneously
but often contract, causing ectropion that must be reconstructed later. Full-thickness
grafts to the lower lids and split-skin grafts to the upper lids may be needed to protect the
globe.
Frostbite
Frostbite injuries commonly occur on the head and neck, most often involving the ears,
cheeks, and nose. These exposed areas are at risk of cold injury because of the body's
response to exposure. Sympathetic excitation causes peripheral vasoconstriction, shunts
blood away from the skin, and reduces heat loss. Local hypothermia occurs as the skin
temperature drops toward that of the ambient air. No serious damage occurs until tissue
freezes. Large ice crystals form and draw water out of the cells. Cell death is caused by
temperature injury or from the intracellular hyperosmolar state. Tissue freezing also
causes vascular sludging and stasis.
Management of frostbite is based on several principles. The patient is brought into a
warm environment as soon as possible. Local rewarming is done by immersing the
involved part in a bath maintained at 100F to 108F (37.8C to 42.3C). Rewarming can
be painful, and narcotic analgesia may be needed. The vascular reaction to frostbite can
be reversed with antiprostaglandin agents and vasodilators. Applying antithromboxane
agents such as aloe vera can help reduce ischemia. Surgical dbridement is delayed until
the extent of injury can be assessed.

HIGHLIGHTS
Accurate, careful technique, gentle tissue handling, and
meticulous cleaning are essential.
Reapproximating landmarks such as the vermilion border with
a key stitch avoids unsightly stepoffs.
Judicious undermining and appropriate use of subcutaneous
sutures reduce tension on the wound.
Placing many small sutures close to the wound margin and to
each other minimizes scarring.
Liberal use of the headlight or microscope improves
visualization and results.
Antibacterial ointments are applied daily to reduce crusting,
itching, and the risk of infection.
Facial nerve injuries posterior to the lateral canthus must be
explored and repaired within 72 hours.
Eyelid injuries suggest underlying globe or lacrimal damage.
Ophthalmologic consultation is obtained.
Microvascular replantation provides the best results in the
management of auricular avulsion but can be technically
difficult and uncertain.
Most animal bites occur among children younger than 10 years
and are inflicted by dogs.
The head and neck are most commonly injured by burns,
although airway injuries are the leading cause of death at burn
centers.
Early excision and grafting of head and neck burns provide
superior aesthetic and functional results.
CHAPTER REFERENCES
1. Nakhgevany KB, LiBassi M, Esposito B. Facial trauma in motor vehicle accidents: etiological
factors. Am J Emerg Med 1994;12:160163.
2. Murphy RX Jr, Birmingham KL, Okunski WJ, et al. The influence of airbag and restraining
devices on the patterns of facial trauma in motor vehicle collisions. Plastic Reconstr Surg
2000;105:516520.
3. Fatovich DM, Jacobs IG. A randomized controlled trial of oral midazolam and buffered lidocaine
for suturing lacerations in children. Ann Emerg Med 1995;25:209214.
4. Brown CD, Zitelli JA. Choice of wound dressings and ointments. Otolaryngol Clin North Am
1995;28:10811091.
5. Reiter D. Methods and materials for wound management. Otolaryngol Head Neck Surg
1994;110:550556.
6. Quinn J, Wells G, Sutcliffe T, et al. A randomized trial comparing octylcyanoacrylate tissue
adhesive and sutures in the management of lacerations. JAMA 1997;277:15271530.
7. Simon HK, Zempsky WT, Bruns TB, et al. Lacerations against Langer's lines: to glue or suture? J
Emerg Med 1998;16:185189.
8. Coker NJ. Management of traumatic injuries to the facial nerve. Otolaryngol Clin North Am
1991;24:215.
9. Turpin IM. Microsurgical replantation of the external ear. Clin Plast Surg 1990;17:397.
10.
11. Nguyen TT, Gilpin DA, Meyer NA, et al. Current treatment of severely burned patients. Ann Surg
1996;223:1425.
12. MacAfee KA, Zeitler DL, Mayo K. Burns of the head and neck. In: Fonseca RJ, Walker RV, eds.
Oral and maxillofacial trauma. Philadelphia: WB Saunders, 1991:702.
13. Pruitt BA, Cioffi WG, Shimazu T, et al. Evaluation and management of patients with inhalation
injury. J Trauma 1990;30:S63.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

65 MANDIBULAR FRACTURES
Head & Neck SurgeryOtolaryngology
65




MANDIBULAR FRACTURES
JOSEPH L. LEACH
MARK T. NEWCOMER

J.L. Leach: Department of Facial Plastic and Reconstructive Surgery, University of Texas Southwestern
Medical Center, Dallas, Texas.
M.T. Newcomer: Department of OtolaryngologyHead and Neck Surgery, University of Texas
Southwestern Medical Center, Dallas, Texas.


Anatomy
Biomechanics of the Mandible
Evaluation and Diagnosis
History
Physical Examination
Radiographic Evaluation
Management
General
Closed Reduction
Open Reduction
Symphysis-Parasymphysis Area
Body
Angle
Ramus
Condyle and Condylar Neck
Special Considerations
Edentulous Fractures
Treatment by Means of Observation Only
Pediatric Fractures
Management of Teeth in the Line of Fracture
External Fixation
Removal of Hardware
Complications
Emergencies
Future Considerations
Chapter References
After the nose, the mandible is the second most commonly fractured facial bone.
Mandibular fractures are probably the most common facial fracture necessitating
treatment. Because of its position surrounding the salivary pool in the floor of the mouth
and its intimate supporting function for half of the dentition, the complication and
infection rates for mandibular fractures far exceed those of fractures of other facial bones
(1).
ANATOMY
The mandible articulates with the skull base at the paired temporomandibular joints and
is suspended by a complex masticatory neuromuscular apparatus. A complete bony ring
is thus formed by the skull and mandible. This ringlike structure contributes to the
tendency for fractures to occur at two separate sites as the result of trauma. Anatomic
components of the mandible include the symphysis, parasymphysis, body, angle, ramus,
coronoid process, condyle, and alveolus. Inherent sites of weakness include the third
molar area (especially if the third molar is impacted), the socket of the canine tooth, and
the condylar neck.
Knowledge of the occlusion is integral to the diagnosis and management of all facial
fractures. In the Angle classification of occlusion the mesiobuccal cusp of the maxillary
first molar is used as a reference (Fig. 65.1). Class I occlusion is the norm. Class II
represents retrognathism, and Class III represents prognathism. Cognizance of the three
classes of occlusion and careful examination of the teeth for wear facets and cuspal
interdigitation allow accurate restoration of the patient's preinjury bite. The universal
dental numbering system is useful in describing the location of mandibular fractures and
reporting associated dental injuries (Fig. 65.2).

FIGURE 65.1. The Angle classification of occlusion is
based on the relation of the mesiobuccal cusp of the
maxillary first molar to the buccal groove of the
mandibular first molar.



FIGURE 65.2. The universal numbering system for the
permanent dentition begins with the maxillary right third
molar. Similarly, the 20 teeth of the deciduous dentition
are lettered from A to T, beginning with the maxillary
right second deciduous molar.



Biomechanics of the Mandible
Mandibular fractures are described as favorable when muscles tend to draw the fragments
toward each other and reduce the fracture and as unfavorable when the fragments tend to
be distracted. Fractures can be vertically or horizontally favorable or unfavorable (Fig.
65.3). Almost all fractures of the angle are horizontally unfavorable. The masseter,
medial pterygoid, and temporalis muscles contribute to displacement of the posterior
segment. Vertically unfavorable fractures most often involve the body and symphysis-
parasymphysis areas and are primarily distracted by the mylohyoid muscle. Closed
reduction usually is limited to favorable fractures, but open reduction with rigid fixation
techniques can be applied in either situation.

FIGURE 65.3. Horizontally unfavorable fracture of the
angle shows displacement in a vertical direction owing to
the action of the masticatory muscles. A vertically
unfavorable body fracture is distracted horizontally by the
mylohyoid bone.



Biomechanically the mandible can be considered a cantilever beam. The beam is
suspended at two points, which represent the temporomandibular joint (TMJ) attachment.
The muscles of mastication produce forces that act on this beam, and the teeth act as
fulcrums. In the mandibular body and angle, forces produce zones of relative tension or
distraction along the inferior border and compression along the superior border (2). In the
symphyseal area, however, the situation is more complicated. Compression is produced at
the upper border, and tension and torsional forces exist along the lower border (2).
Tension and compression forces dictate the type of fixation applicable to a particular
fracture.
EVALUATION AND DIAGNOSIS
History
Pain and malocclusion after a blow to the lower face strongly suggest mandibular fracture
(Table 65.1). Additional symptoms include anesthesia of the lower lip and chin caused by
trauma to the inferior alveolar nerve in its course through the mandibular canal.

TABLE 65.1. DIAGNOSIS MANDIBULAR
FRACTURE



Physical Examination
Fractures of the symphysis-parasymphysis and body can be accompanied by hematoma
in the floor of the mouth or laceration of the attached gingiva adjacent to the teeth.
Mobility of fractures in these locations often can be identified by means of palpation.
Trismus is a relatively constant finding with mandibular fractures, but it also occurs after
facial contusions without fracture. The interincisal opening of a patient with a mandibular
fracture usually measures 35 mm or less because of muscle splinting; the lower limit of
normal is 40 mm.
Fractures of the condyle and condylar neck are associated with impaired translational
movement of the condyle along the articular eminence. Although limited rotation can
occur, this lack of translation produces a characteristic deviation of the chin on opening
toward the side of such a fracture (Fig. 65.4). Fractures of the neck of the condyle tend to
be displaced anteromedially in response to the action of the lateral pterygoid muscle. This
displacement produces a loss in the functional height of the ramus, which allows
premature contact of the ipsilateral molar teeth. The point of contact acts as a fulcrum and
produces a characteristic open bite on the side opposite the fracture (Fig. 65.5).
Bilaterally displaced fractures of the necks of the condyles produce a symmetric anterior
open bite.

FIGURE 65.4. A fractured condyle does not translate
down the articular eminence on jaw opening. The
unopposed translational movement of the opposite
condyle deviates the chin toward the side of the fractured
condyle.



FIGURE 65.5. A fractured condyle usually is distracted
anteromedially by the lateral pterygoid muscle. This
produces a shortened functional height of the ramus as
the masseter, medial pterygoid, and temporalis muscles
draw the ramus closer to the skull base. The ipsilateral
molar teeth act as a fulcrum to produce a slight
contralateral anterior open bite.



Radiographic Evaluation
The single best radiograph for evaluation of mandibular fractures is the panoramic view
(Fig. 65.6). A mandibular series of plain radiographs often provides additional
information, especially about the neck of the condyle, ramus, and symphysis. Computed
tomography is less reliable than radiography for identifying minimally displaced
mandibular fractures.

FIGURE 65.6. Panoramic radiograph of an avulsive
mandibular fracture from a shotgun blast. Screws from
the external fixation system are present.



MANAGEMENT
General
Table 65.2 summarizes treatment options for adult patients. All fractures involving the
tooth-bearing part of the mandible should be considered compounded into the mouth.
These fractures necessitate antibiotic prophylaxis starting as soon as possible after the
injury and ending when a watertight mucosal seal has been reestablished. Depending on
the severity of the fracture, this can range from 24 hours to several weeks after reduction.
Topical oral antiseptics also help minimize the bacterial inoculum of the fracture site.
Although delay of fracture repair for several days does not seem to increase the
complication rate, consideration of patient comfort warrants intervention as soon as
possible. Marked displacement of the jaw fragments is uncomfortable for the patient,
impairs oral hygiene and alimentation, and grossly soils the exposed bone with bacteria-
laden saliva.

TABLE 65.2. TREATMENT OPTIONS FOR
DENTATE ADULT PATIENTS



Closed Reduction
Most favorable fractures in adult patients can be managed by means of closed reduction
with arch bars or another means of interdental wiring. More than half of all mandibular
fractures are amenable to closed reduction (3). Six weeks of intermaxillary fixation (IMF)
usually is considered appropriate, although 4 weeks has been advocated (4).
Open Reduction
The classic indication for open reduction and internal fixation has been anticipated
fragment displacement despite closed reduction. Many fractures can be approached
transorally to avoid an external scar. Internal fixation can be classified as being rigid
(reconstruction plates, compression plates, lag screws), semirigid (miniplates), or
nonrigid (interosseous wires). Most rigid and some semirigid techniques obviate
prolonged IMF. This is an especially important consideration among patients with
epilepsy, diabetes, alcoholism, psychiatric disorders, or severe debility, who may not
tolerate IMF. Rigid and semirigid internal fixation requires more hardware and greater
cost. More extensive periosteal stripping and more manipulation of soft tissues are
required. Because more holes have to be drilled, there is a higher incidence of nerve
injury (5).
Compression plates and lag screws produce interfragmentary compression of bone,
whereas the other techniques do not. The large dynamic compression or eccentric
dynamic compression plates usually require an external approach. Damage to the facial
nerve and soft-tissue scarring can result (6). Bending of plates is difficult with the system,
and malocclusion rates up to 23% have been reported (6). Fractures that follow a fairly
straight course from buccal to lingual cortices lend themselves easily to compression
plate osteosynthesis, but sagittal or oblique fractures should not be subjected to axial
compression (7). Sagittal and oblique fractures may be more amenable to repair with lag
screw techniques. To achieve optimal compression without displacement, a lag screw
hole is drilled along a line as close to perpendicular to the fracture line as possible.
Compression is not used in cases of infection or comminution (8). In such instances, large
reconstruction plates and 2.7-mm or 2.4-mm screws are considered. These plates ideally
require placement of at least three screws in the peripheral fracture segments. Although
reconstruction plates do not produce compression of the fracture segments, they do
produce rigid fixation.
Symphysis-Parasymphysis Area
The lack of occlusal stops and locks in the anterior teeth produces special problems in the
symphyseal and parasymphyseal region. Closed reduction is difficult in this area.
Vertically unfavorable symphyseal fractures tend to collapse the mandibular arch in
response to the mylohyoid muscle. To resist this scissors-like collapse, closed reduction
techniques often include application of a custom acrylic lingual splint in addition to IMF.
Open reduction with rigid internal fixation avoids both the splint and the need for IMF.
The use of a rigid technique necessitates application of an arch bar and temporary
intraoperative interdental wiring. The mandibular arch bar provides initial tension at the
superior mandibular border. Compression at the inferior border can be provided with a
contoured reconstruction plate or several lag screws (9) (Fig. 65.7). Because vertically
unfavorable fracture segments tend to telescope, use of bicortical compression plates to
establish normal occlusion is particularly difficult in this region (10).

FIGURE 65.7. Initial tension compression at the superior
mandibular border provided by the arch bar. The
compression plate is slightly overbent and is applied with
bicortical screws. Alignment of one screw through the
fracture site can add lag screw compression.



Body
Transoral application of a compression plate to fractures posterior to the mental foramen
is difficult, although semirigid techniques can be applied transorally in this area with
greater ease. An eccentric dynamic compression plate can be applied through a large
external incision with precompression of the fracture with a special pliers and the arch
bar as a tension band. If the fracture is oblique or comminuted, use of a large
reconstruction plate is an option, but a large external incision is necessary. Multiple lag
screw fixation is a third alternative. Anterior body fractures coursing through the mental
foramen can be managed by means of placing an inferior lag screw through a cutaneous
stab incision and a monocortical miniplate tension band transorally above the mental
foramen (Fig. 65.8). Either of the lag screw options offers enough rigidity to obviate IMF
and avoid the large cervical scar associated with the external technique.

FIGURE 65.8. A, B: Double lag screws are placed in a
fracture of the symphysis, and a single oblique lag screw
is placed in the angle fracture. C: Body fracture through
the mental foramen is managed with a miniplate and
monocortical screws above the foramen and a single lag
screw below.



Angle
Fractures of the angle are associated with the highest incidence of infection (11). The
relatively small cross-section of bone in this region and the oblique and irregular fracture
configurations make compression osteosynthesis particularly unfavorable (11). Transoral
placement of a single tension-band miniplate (noncompression with monocortical screws
2.0 mm in diameter) near the superior border has been used as an alternative to
interosseous wiring, although inferior border displacement with masticatory loading has
been described (12). Applying a second miniplate to the buccal cortex has been shown to
decrease the complication rate, even without the use of IMF (13). The external approach,
with application of either a large eccentric dynamic compression plate or both a dynamic
compression plate and a tension band miniplate, provides rigid fixation but requires a
large external incision. The single oblique lag screw technique (14) provides solid
fixation and avoids both IMF and a large external incision. Each of these techniques is
effective; selection is based on the suitability of overlying lacerations, availability of
equipment, and physician experience.
Ramus
Fractures of the ascending ramus are naturally splinted by the pterygomasseteric sling
and are amenable to closed reduction. This splinting effect allows early release of IMF
for nondisplaced fractures (3 to 4 weeks). Access to this area for plating, either
transorally or extraorally, is somewhat difficult unless overlying lacerations are present.
Condyle and Condylar Neck
The indications for open reduction of condylar fractures remain debatable and have been
summarized by Zide and Kent (15) (Table 65.3). Fractures in this area usually are
managed by means of closed reduction, although an overlying laceration can facilitate
application of a miniplate to the condylar neck. Fractures within the capsule of the TMJ
are not opened and are managed by means of closed reduction.

TABLE 65.3. INDICATIONS FOR OPEN
REDUCTION OF MANDIBULAR CONDYLE
FRACTURES



Exercise sessions every 2 weeks allow a brief release from IMF to avoid intra- and
periarticular fibrosis and ankylosis. The duration of IMF varies with the severity of the
condylar fracture. Nondisplaced fractures can be managed with 3 weeks of IMF followed
by 2 weeks of night elastic-band fixation. Displaced fractures require 6 weeks of IMF,
followed by several more weeks of night elastic fixation if a contralateral anterior open
bite develops after release of fixation. Techniques with endoscopic approaches and
instrumentation for fracture reduction and fixation have been described (16).
SPECIAL CONSIDERATIONS
Edentulous Fractures
The classic management of an edentulous mandibular fracture has been closed reduction
in which arch bars are applied to the patient's dentures to allow IMF. If dentures are not
available, Gunning splints can be fabricated. The dentures or Gunning splints are secured
to the maxilla with circumzygomatic and anterior nasal spine wiring, Kirschner pinning
through the alveolus, or screws into the palate. Fixation to the mandible is achieved with
three circummandibular wires. The inherently poor hygiene of dentures or splints makes
IMF extremely onerous for an edentulous patient, and rigid techniques often are used to
manage edentulous fractures without advanced mandibular atrophy. Markedly atrophic
mandibles tend to fracture at the weakest point in the midbody, where the diameter of the
jaw can be that of a pencil (Fig. 65.9). Inadequate bone is present for rigid fixation, and
nonunion is a frequent complication. Aggressive surgical management (sandwiching the
fracture between split ribs and packing the site with autogenous iliac marrow) often is
successful (17). However, many patients are elderly or debilitated, and the need for this
major surgery must be balanced against the patient's medical condition.

FIGURE 65.9. The atrophic, edentulous mandible often
fractures at the midbody, where the atrophy is most
advanced.



Treatment by Means of Observation Only
Some patients can be treated with a liquid to soft diet and careful follow-up evaluation.
Such situations include a unilateral nondisplaced fracture of the condylar area in which
patients can easily bite to their normal occlusion. If malocclusion is present after
periarticular edema resolves, closed reduction is performed. Nonoperative management
of condylar fractures can be used more liberally for edentulous patients, who can tolerate
moderate degrees of condylar displacement. New dentures can compensate for the change
in jaw relations.
Pediatric Fractures
Almost all fractures involving the deciduous dentition can be managed by means of
closed reduction for 2 to 3 weeks. Rigid techniques place the developing tooth buds at
risk and usually are avoided. The most dreaded complication of pediatric jaw fractures is
the development of ankylosis of the TMJ, which can alter jaw growth and produce a
severe facial deformity. Ankylosis is best avoided in the management of pediatric
condylar fractures by allowing weekly mobilization of the jaw with a rapid return to
normal jaw function.
The crest of the curvature of the crown of a deciduous tooth is closer to the gingival
margin than is the crown of a permanent tooth, making placement of periodontal wire
ligatures difficult but not impossible. Intermaxillary fixation can be established easily by
means of direct skeletal wiring with 24-gauge wires passed through holes drilled in the
inferolateral margin of the piriform rim and wired directly to circummandibular wires
(Fig. 65.10). Such skeletal wiring also helps reinforce arch bar fixation for adults whose
anterior dentition is partially missing or unstable.

FIGURE 65.10. Arch bar application can be avoided in
deciduous or mixed dentition by means of direct skeletal
wiring from the piriform rims to circummandibular wires.



Management of Teeth in the Line of Fracture
It is generally agreed that teeth with fractured roots must be removed. Much controversy
has arisen, however, regarding the retention of uninjured, stable teeth in the line of a
mandibular fracture. Although each situation must be evaluated individually, most such
teeth can be and are retained (18).
External Fixation
Stabilizing mandibular defects and fractures by means of external fixation is particularly
applicable in contaminated gunshot wounds resulting in loss of part of the mandible (19)
(Fig. 65.11). Although rigid fixation with implantation of a three-dimensional
reconstruction plate can be used in this instance, external fixation provides the advantage
of fragment stability with neither IMF nor a foreign body in the wound and allows access
to the wound for subsequent dbridement and hygiene.

FIGURE 65.11. A: Percutaneous bicortical placement of
the external fixator screw. B: Application of the primary-
phase hardware allows precise alignment of the fracture
or defect. C: The acrylic bar is applied and cured in the
second phase, and the primary-phase hardware is
removed.



Removal of Hardware
The need for hardware removal is controversial. Titanium, unlike the stainless steel used
in older plates, forms an intimate association with bone that makes miniplate removal
technically difficult and probably unnecessary.
COMPLICATIONS
Table 65.4 lists complications of mandibular fractures. The infection rate for mandibular
fractures is about 10%, and the incidence of osteomyelitis is approximately 3% (20,21).
Osteomyelitis can lead to nonunion, and subsequent bone grafting can be done after
adequate resolution of infection. Infection does not seem to be consistently linked to
transoral open reduction or retention of a tooth in the line of fracture (22,23).

TABLE 65.4. COMPLICATIONS
MANDIBULAR FRACTURES



In one study, a 1.1% rate of malocclusion was found among patients treated with rigid
techniques (24). Marked malocclusion immediately after rigid fixation is probably caused
by an error in fragment alignment and is permanent unless corrected by means of prompt
revision surgery. Standard orthognathic surgical techniques can be used to correct
malocclusion due to malunion of jaw fractures. Although posttraumatic TMJ ankylosis is
rare, the true incidence of TMJ dysfunction after mandibular fracture is difficult to
establish because of the subjective nature of the assessment and the prolonged time that
often elapses before an internal joint injury manifests itself. Sensory disturbances of the
inferior alveolar nerve are common after mandibular fracture, but traumatic neuroma
formation is rare.
EMERGENCIES
Emergencies related to mandibular fractures are listed in Table 65.5. Bilateral fractures of
the mandibular body can cause posterior displacement of the anterior mandibular arch
owing to the presence of the suprahyoid musculature. This can necessitate precipitous
airway impairment, especially when the patient is in the supine position. Immediate
intervention is needed by placing the patient in the lateral decubitus position and
temporarily wiring the teeth together or by means of establishing an airway by means of
intubation or tracheotomy. Cerebrospinal otorrhea can herald displacement of a condylar
head into the middle cranial fossa. Such an injury can be associated with a dural tear;
neurosurgical consultation and prompt open reduction are appropriate. Concomitant
injury to the adjacent internal carotid artery occasionally occurs in conjunction with
fractures of the condylar neck. The presence of a severely displaced fracture can prompt
further investigation into the integrity of the adjacent carotid artery. Gross hemorrhage
rarely accompanies mandibular fracture, but troublesome bleeding occasionally arises
from the inferior alveolar artery within the mandibular canal. Ligation of this vessel is
difficult, and temporary reduction of the fracture effectively tamponades the bleeding
site.

TABLE 65.5. EMERGENCIES MANDIBULAR
FRACTURES



FUTURE CONSIDERATIONS
The surging popularity of rigid fixation to manage mandibular fractures has left
unanswered questions about the advisability and timing of the removal of fixation
hardware. Concerns over stress shielding and possible delayed infection in the mandible
cannot be addressed by inference from orthopedic data. Endoscopic approaches can
reduce the morbidity associated with repair of mandibular fractures. Results of research
on the efficacy of resorbable rigid fixation materials may provide head and neck surgeons
with the ideal mandibular fracture fixation device.

HIGHLIGHTS
The chin deviates when opened toward the side of a fractured
condyle.
Almost all condylar fractures are managed by means of closed
reduction.
Fractures of the condylar neck are associated with anteromedial
displacement of the condyle owing to the action of the lateral
pterygoid muscle.
Almost all fractures of the mandibular angle are unfavorable
and necessitate open reduction.
When evaluating a mandibular or TMJ injury, it is helpful to
measure the maximum interincisal opening; the lower limit of
normal is 40 mm.
Bilaterally displaced fractures of the condyles are associated
with a symmetric anterior open bite.
In almost all cases, teeth in the line of a mandibular fracture are
preserved.
Among children, posttraumatic ankylosis of condylar fractures
produces severe developmental facial asymmetry.
Bilateral fractures of the mandibular body, especially in
edentulous patients, can allow the anterior arch of the mandible
to fall posteriorly and obstruct the airway.
When malocclusion is detected immediately after open
reduction with rigid fixation, revision surgery usually is needed
to correct the error in fragment alignment.
CHAPTER REFERENCES
1. Chole RA, Yee J. Antibiotic prophylaxis for facial fractures. Arch Otolaryngol Head Neck Surg
1987;113:10551057.
2. Rudderman RH, Mullen RL. Biomechanics of the facial skeleton. Clin Plast Surg 1992;19:1121.
3. James RB, Fredrickson C, Kent JN. Prospective study of mandibular fractures. J Oral Surg
1981;39:275.
4. Chuong R, Donoff RB, Guralnick WC. A retrospective analysis of 327 mandibular fractures. J
Oral Maxillofac Surg 1983;41:305.
5. Leach J, Truelson J. Traditional methods vs rigid internal fixation of mandible fractures. Arch
Otolaryngol Head Neck Surg 1995;121:752.
6. Tuovinen V, Norholt SE, Sindet-Pedersen S, et al. A retrospective analysis of 279 patients with
isolated mandibular fractures treated with titanium miniplates. J Oral Maxillofac Surg
1994;52:931935.
7. Ellis E. Complications of rigid internal fixation for mandible fractures. J Craniomaxillofac
Trauma 1996;2:3239.
8. Kearns GJ, Perrott DH, Kaban LB. Rigid fixation of mandible fractures: does operator experience
reduce complications? J Oral Maxillofac Surg 1994;52:226231.
9. Ellis E, Ghali G. Lag screw fixation of anterior mandibular fractures. J Oral Maxillofac Surg
1991;49:13.
10. Busch RF. Mandibular osteosynthesis with intraoral miniplates and cortical bone screws. Ear
Nose Throat J 1995;74:815.
11. Zacharaides N, Papademetriou I. Complications of treatment of mandible fractures with
compression plates. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;79:150153.
12. Kroon FHM, Mathisson M, Lordley JR, et al. The use of miniplates in mandibular fractures. J
Craniomaxillofac Surg 1991;19:199.
13. Levy FE, Smith RW, Odland RM, et al. Monocortical miniplate fixation of mandibular angle
fractures. Arch Otolaryngol Head Neck Surg 1991;117:149.
14. Niederdellmann H, Shetty V. Solitary lag screw osteosynthesis in the treatment of fractures of the
angle of the mandible: a retrospective study. Plast Reconstr Surg 1987;80:68.
15. Zide MF, Kent JN. Indications for open reduction of mandibular condyle fractures. J Oral
Maxillofac Surg 1983;41:8998.
16. Lauer G, Schmeizeisen R. Endoscope assisted fixation of mandibular condylar process fractures. J
Oral Maxillofac Surg 1999;57:3639.
17. Obwegeser HL, Sailer HF. Another way of treating fractures of the atrophic edentulous mandible.
J Maxillofac Surg 1973;1:213.
18. Shetty V, Freymiller E. Teeth in the line of fracture: a review. J Oral Maxillofac Surg
1989;47:1303.
19. Wessberg GA, Schendel SA, Epker BN. Monophase extraskeletal fixation. J Oral Surg
1979;37:892.
20. Andersson L, Hultin M, Nordenram A, et al. Jaw fractures in Stockholm (19781980). Int J Oral
Surg 1984;13:194.
21. Busuito MJ, Smith DJ, Robson MC. Mandibular fractures in an urban trauma center. J Trauma
1986;26:826.
22. Dierks E. Transoral approach to fractures of the mandible. Laryngoscope 1987;97:4.
23. De Amaratunga NA. The effect of teeth in the line of mandibular fractures on healing. J Oral
Maxillofac Surg 1987;45:312.
24. Raveh J, Vuillemin T, Ladrach K, et al. Plate osteosynthesis of 367 mandibular fractures. J
Craniomaxillofac Surg 1987;15:244.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

66 MAXILLARY AND PERIORBITAL FRACTURES
Head & Neck SurgeryOtolaryngology
66




MAXILLARY AND PERIORBITAL FRACTURES
ROBERT B. STANLEY, JR.

R.B. Stanley, Jr.: Department of OtolaryngologyHead and Neck Surgery, Harborview Medical Center,
University of Washington School of Medicine, Seattle, Washington.


Anatomy
Buttress System
Zygoma
Orbit
Pathophysiology
Buttress System Loading
Anterior Impact Forces
Lateral Impact Forces
Orbital Forces
Patient Evaluation
Computed Tomography
Ophthalmologic Evaluation
Management Philosophy
Immediate Reconstruction
Extended Access Approaches
Stable Internal Fixation
Surgical Techniques
Zygoma
Maxilla
Orbital Walls
Complications
Lid Damage
Lip Distortion
Vision Loss
Implant Visibility
Malocclusion
Bioresorbable Implants
Three-Dimensional Computed Tomographic Reconstructions
Intraoperative Computed Tomographic Scanning
Chapter References
Maxillofacial trauma is a serious medical and socioeconomic problem that continues to
increase with each decade (1). Fractures of the facial skeleton were traditionally
evaluated and managed in a segmental manner, even if complex injuries were obvious
during the initial evaluation. This approach usually produced acceptable results if the
fractures were because of low-velocity impact and displacement was minimal. However,
similar successes in managing injuries due to high-velocity impact often were not
achieved. Experienced maxillofacial trauma surgeons have recognized that the
suboptimal results could not always be attributed to the severity of the injury itself but
were instead caused by the segmental approach. Therefore all fractures of the middle
third of the face must be evaluated as possible orbitozygomaticomaxillary injuries and
not as blow-out, malar, or Le Fort fractures. The goal of treatment must be the exact
anatomic restoration of the midfacial skeletal unit rather than random repositioning of
component parts.
ANATOMY
Buttress System
The skeleton of the middle third of the face consists of a system of horizontal and vertical
buttresses that combine to form an intricate latticelike structure that maintains horizontal
and vertical dimensions and that surrounds and protects the orbits, oral cavity, nasal
cavity, and paranasal sinuses. The vertical buttresses include the well-defined paired
nasomaxillary, zygomaticomaxillary, and pterygomaxillary buttresses, which arise in the
maxillary alveolar process and project superiorly to the skull base (Fig. 66.1). All of these
struts have developed as a mechanical adaptation of the skull to masticatory forces. The
greatest occlusal load appears to be borne by the zygomaticomaxillary buttresses, which
originate in the lateral antral wall immediately above the maxillary first molars. Although
the bone of the maxilla is quite thin overall, its lateral wall is formed by a V-shaped
thickened area of compact bone that provides strength for the lower end of this buttress.
The upper two thirds of the zygomaticomaxillary buttress is formed by the zygoma, a
relatively sturdy block of bone.

FIGURE 66.1. The nasomaxillary and
zygomaticomaxillary buttresses of the midfacial lattice
are suspended from the frontal bar.



The vertical buttresses are mostly curved structures and must therefore be reinforced with
horizontal struts. The superior orbital rims and thick bone of the glabellar area form the
frontal bar from which the nasomaxillary and zygomaticomaxillary buttresses are
suspended (Fig. 66.1). In the inferior aspect, the reinforcing connections include the
inferior orbital rims, the maxillary alveolus and palate, the zygomatic processes of the
temporal bones, and the serrated edges of the greater wings of the sphenoid bone.
Zygoma
The zygoma, which forms the cornerstone of the buttress system and provides the
aesthetically important malar prominence, is related to the surrounding craniofacial
skeleton through four superficial and two deep projections. The superficial projections
contribute to two critical external arcs of contour (Fig. 66.2). The vertical arc defines the
course of the zygomaticomaxillary buttress; it runs from the zygomatic process of the
frontal bone over the zygoma to the lateral antral wall. The longer horizontal arc runs
from the maxilla in the area of the lacrimal fossa around the zygoma to the zygomatic
process of the temporal bone. It is parallel to but slightly below the Frankfort horizontal
plane. Because the height of contour of the malar prominence is at or slightly inferior to
the Frankfort plane, the point of intersection of these arcs of contour defines the position
of the malar prominence. The deep projections are the sphenoid projection that articulates
along the lateral orbital wall with the orbital plate of the sphenoid bone and the orbital
floor projection that articulates with the orbital surface of the maxilla in the extreme
lateral aspect of the orbital floor. The sphenoid and orbital floor projections lie beneath
and perpendicular to the external arcs of contour in the area of the inferolateral orbital
rim, greatly strengthening this portion of the rim.

FIGURE 66.2. Vertical and horizontal external arcs of
contour (zygomatic complex). Intersection at X (dashed
lines) marks the position of the malar prominence.



Orbit
The bony prominences that form the superior, lateral, and inferior portions of the orbital
rim usually are palpable and often are visible through the soft-tissue covering. No true
medial rim exists in the area of confluence of the orbit, lacrimal fossa, glabella, and nasal
dorsum. The greatest diameter of the orbit is approximately 1.5 cm posterior to the
inferior orbital rim, where the orbital roof has an upward convexity that places it
approximately 5 mm above the superior orbital rim. The orbital floor is concave with a
depth of approximately 3 mm in relation to the inferior orbital rim. The globe itself rests
within this concavity (Fig. 66.3). In the posterior aspect, the floor is convex. In the
posteromedial aspect it slopes upward into the medial orbital wall without a sharp
demarcation (Fig. 66.4). Laterally and posteriorly the floor is separated from the greater
wing of the sphenoid bone by the inferior orbital fissure. The optic foramen lies
posteriorly in the plane of the medial orbital wall; it thus is medial and superior to the
true orbital apex (Fig. 66.4).

FIGURE 66.3. Longitudinal section of the orbit. The
globe lies in the area of the concave portion of the orbital
floor, and the retrobulbar soft tissues are supported by the
convex posterior floor. The millimeter scale identifies the
position of the two areas of opposite floor contour
relative to the inferior orbital rim and orbital apex.



FIGURE 66.4. The convex posterior orbital floor (large
arrow) slopes gradually into the medial wall. A dissection
40 mm into the orbit from the inferior rim (Fig. 66.3) may
be needed for repair of this area. The optic foramen
(small arrow) is immediately medial and superior to this
posterior limit of dissection.



PATHOPHYSIOLOGY
Buttress System Loading
The honeycomb construction of the middle third of the face provides excellent stability as
long as it is loaded in the application for which it was intendedto resist predominantly
vertical masticatory forcesand as long as the lattice remains intact. Although the fairly
strong vertical buttresses bear the load of mastication, the weaker horizontal reinforcing
buttresses must absorb external impact directed at the middle third of the face. The
disruption of a single buttress can weaken the entire lattice and cause its collapse.
However, random collapse under anterior or lateral impact usually is prevented by the
strength of the horizontal buttresses combined with their relation to the base of the skull.
Anterior Impact Forces
Anterior impact causes recurring fracture patterns that tend to follow the three weak lines
of the midfacial skeleton, as described by Le Fort (Fig. 66.5). Because anterior impact
usually is not perfectly centered, Le Fort fractures usually occur in unpredictable
combinations. Most often, the patterns are asymmetric with the level of injury higher on
one side than the other. The injuries range from isolated, minimally displaced Le Fort I,
II, or III fractures to multiple, widely displaced fracture dislocations that cause gross
malalignment of the buttresses. This malalignment is evident clinically as a combination
of maxillary retrusion or rotation, midfacial elongation, and malocclusion. An actual
reduction in midfacial height is a rare occurrence caused by severe impact that drives the
mandible superiorly into the maxilla to shatter the vertical struts and shorten midfacial
vertical dimension.

FIGURE 66.5. Le Fort fracture levels. Although these
levels usually do not describe the extent or exact nature
of midfacial fractures, they are still appropriately used for
a general description of the injuries.



Lateral Impact Forces
Unlike anterior impact, lateral forces do tend to be centered on a convenient target, the
prominent convex outer surface of the zygoma. These forces usually are absorbed
through fragmentation of the weaker bones with which the zygoma articulates (Fig. 66.6),
with two exceptions. The stout zygomatic process of the frontal bone is almost always
spared by the typical clean separation of the zygomaticofrontal suture. The zygomatic
arch sustains a single fracture near its midpoint or a double fracture that produces a
displaced and possibly rotated large central fragment. The degree of fragmentation at the
other projections of the zygoma depends on the velocity of the impact, and even
comminuted Le Fort fractures are caused by cross-facial transmission of high-velocity
lateral forces.

FIGURE 66.6. External arcs of contour of the zygoma
disrupted (dotted lines) with comminution of the inferior
orbital rim and lateral antral wall. Totally accurate three-
point reduction of the lower end of the vertical arc and
the anterior end of the horizontal arc may not be possible.
Open reduction of the zygomatic arch may be needed.



Orbital Forces
Within the orbit, impact is transmitted through the zygoma and the sphenoidal and orbital
processes to the deeper structures. The floor of the orbit almost always sustains
comminuted injury to the concave central portion of the floor, the severity of which
varies with the strength of the impact. High-velocity periorbital impact can be transmitted
to the convex posterior floor and even to the medial wall and cause serious displacement
of the bone in these areas. The force sometimes is centered slightly higher over the lateral
orbital rim, and it must be absorbed by a fairly weak sphenotemporal buttress formed by
the zygoma, orbital plate of the greater wing of the sphenoid bone, and the squamous
portion of the temporal bone. If the ability of this buttress to absorb impact is exceeded,
fracture dislocations of the lateral orbital wall occur, and the orbital plate of the sphenoid
bone can be forced into the orbital apex or into the middle cranial fossa.
The position of the globe is determined by the integrity of the orbital walls and the
extensive network of ligaments that suspend it. Recession or depression of the globe
within the orbit is caused by any injury that pushes one or more orbital walls outward and
damages the network of suspensory ligaments. The orbital soft tissues are displaced by
gravitational forces and the remodeling forces of fibrous scar contracture. This usually
changes the shape of the orbital soft tissues from a modified cone to a sphere, and the
globe sinks backward and downward.
PATIENT EVALUATION
Computed Tomography
Evaluation of a patient with maxillary and periorbital trauma has been greatly improved
by the use of high-resolution computed tomography (CT). Axial and coronal scans can be
used to show the fracture lines through the entire facial skeleton (Table 66.1). The
expense of CT evaluation of patients with facial fractures other than simple nasal and
mandibular fractures appears justified.

TABLE 66.1. DIAGNOSIS CRITICAL AREAS
IN CT EVALUATION OF
ORBITOZYGOMATICOMAXILLARY
FRACTURES



The buttress system, particularly the vertical struts, must be systematically inspected
preoperatively to document the degree of malalignment because of fracture fragment
displacement. Fracture lines themselves through the buttresses do not mandate open
reduction, but comminution and gross malalignment strongly suggest the need for
reduction of the fractures under direct visualization to restore facial length and projection
(Fig. 66.7A, Fig. 66.7B). Computed tomographic scans can show fractures of the
condylar head, condylar neck, and vertical ramus of the mandible (Fig. 66.7C). The status
of these structures must be known before fracture dislocations of the maxilla are placed
into occlusion with the mandible.

FIGURE 66.7. A: Fracture patterns thought to be present
at clinical examination of a patient who sustained a high-
velocity impact to the lower midfacial level and
mandible. Axial CT scans show (B) a displaced para
sagittal fracture (arrow) of the palate and (C) bilateral
displaced condylar head fractures (arrows). Accurate
restoration of the position of the maxilla could not be
achieved simply by placing this patient into
maxillomandibular fixation.



The arcs of contour of the zygoma and the walls of the orbit are evaluated for decisions
about the need for surgery and the appropriate operative approach. The CT finding of
comminution and dislocation of both ends of the horizontal arc of contour indicates that
exact reconstruction of the orbitozygomatic complex can be achieved only if the
zygomatic arch is exposed and repaired (Fig. 66.8). Within the orbit itself, evaluation of
the floor and medial wall is critical, especially in the areas of the convex posterior floor
and the gentle slope of the floor into the medial wall. This evaluation requires a true
coronal CT scan (Fig. 66.9) or a three-dimensional reconstruction from an axial scan.
High-resolution studies allow accurate calculation of orbital volume changes related to
specific defects of the orbital walls. Orbital injuries likely to produce enophthalmos are
those in which disruption of the orbital floor exceeds a total area of 2 cm
2
, the bone
volume changes exceed 1.5 cm
3
(5% of orbital volume), or considerable fat and soft-
tissue displacement occur (2). Three-millimeter displacement of the inferior or medial
wall causes an orbital volume change of 7% to 12%. These changes can produce 2.5 to
4.0 mm of globe displacement if no change in orbital contents occurs (3).

FIGURE 66.8. A: Axial CT scan shows severe fracture
dislocation of the right zygoma that resembles the
schematic injury depicted in Fig. 66.6. The amount of
movement needed to reposition the malar prominence
correctly is shown by the arrow. The dotted white line
along the left zygomatic arch indicates the straight central
segment that must be reconstructed on the right. B:
Coronal scan of the same patient. The true extent of the
comminuted, displaced orbital floor fracture (arrow) would not be appreciated clinically
because of the impaction of the zygoma.



FIGURE 66.9. True coronal CT scan shows
displacement of the convex posterior orbital floor and the
entire medial orbital wall. The increase in posterior
orbital volume on the right side is made obvious when the
correct position of these structures is shown (dotted line).



It is no longer acceptable to adopt a wait-and-see attitude about possible delayed
sequelae, such as enophthalmos, and it is no longer acceptable to perform orbital
exploration through an incision that violates the lower eyelid just to evaluate the status of
the orbital floor. Doing so places the patient at risk of the iatrogenic complications of lid
retraction or eversion. Enophthalmos may not be detected immediately, even after severe
orbitozygomatic fractures. If the body of the zygoma has remained intact, it can be
impacted medially to compensate for the increased orbital volume caused by blow-out
injuries to other walls (Fig. 66.8B), and the globe can appear to have normal anterior
projection and vertical position. However, reduction of the zygomatic component of the
injury to restore the malar prominence unmasks the traumatic increase in orbital volume
and leads to delayed-onset enophthalmos if the other fractures are not managed. Careful
review of axial and coronal CT scans can prevent this error.
Ophthalmologic Evaluation
Complete preoperative ophthalmologic evaluation of every patient who has sustained an
orbitozygomatic fracture is an unrealistic expectation. However, reconstructive surgeons
must be sensitive to the possibility of direct ocular trauma and obtain proper consultation
if indicated. A minimal preoperative examination includes testing of visual acuity
(subjective and objective in both eyes), pupillary function, and ocular motility; inspection
of the anterior chamber for hyphema; and visualization of the fundus for gross disruption.
A decrease in visual acuity or any abnormality observed on the other phases of this
screening examination warrants detailed examination by an ophthalmologist before
reconstruction of the bony injuries is undertaken. The value of forced duction testing for
muscle entrapment has diminished with the increased use of CT to document the status of
the orbital walls.
MANAGEMENT PHILOSOPHY
Immediate Reconstruction
The goal of modern fracture management is near-total or total initial reconstruction of the
bony architecture of the injured facial skeleton. Immediate reconstruction usually is less
difficult and more successful than delayed reconstruction, mainly because the latter can
be complicated by cicatricial contraction of the facial soft tissues if the underlying
skeletal support collapses or is lost. During the acute phase of injury, the soft tissues are
pliable enough to allow restoration of the underlying bony configurations with local bone
fragments or autogenous bone grafts. If the soft tissues are allowed to contract into a bone
defect, restoration of the soft tissue to a normal position by delayed restoration of the
supporting bone invariably produces a less desirable result. If revision surgery for minor
residual bone defects or lacerations is required, it is greatly facilitated if the overall soft-
tissue envelope has been maintained in a normal position.
Extended Access Approaches
Paralleling advances in radiographic evaluation of facial fractures has been the
development of extended access approaches that allow more accurate reduction of
fracture displacements. The zygoma and all of its projections, including the zygomatic
arch, and all walls of the orbit can be safely and almost totally exposed through a
combination of coronal, sublabial, and transconjunctival incisions. Dissection of the
orbital floor often cannot be limited to the concave area immediately behind the orbital
rim but must be extended deeply into the orbit to repair the convex posteromedial floor.
Deep dissection to within 5 to 10 mm of the orbital apex may be needed to return the
orbital soft tissues as completely as possible to their normal location and for placing
grafts for restoration of the normal shape and volume of the orbit (Fig. 66.3). The lower
ends of the vertical buttresses can be exposed through extended sublabial incisions that
essentially deglove the maxilla. Although this frequently removes all residual external
periosteal attachments to displaced maxillary fracture fragments, bony union should
proceed in a timely manner if the fragments are adequately stabilized and the periosteum
is redraped over them.
A surgeon may be hesitant to perform these extended access approaches in favor of more
limited approaches in the hope that any facial asymmetry resulting from incomplete
fracture reduction will be imperceptible. However, the range of imperceptible asymmetry
is small, and the surgeon cannot rely on it to hide suboptimal results that might have been
improved with more extensive reconstruction.
Management of fractures of the tooth-bearing segments of the midfacial skeleton has
evolved a great deal from the traditional triad of closed reduction, maxillomandibular
fixation, and craniofacial or circumzygomatic suspension. Closed manipulation of the
maxilla to obtain maximal interdigitation of the teeth before application of
maxillomandibular fixation restores the position of the maxilla in the horizontal plane if
the mandible is correctly related to the skull base. However, it does not automatically
reestablish midfacial height if the vertical buttresses have been disrupted by fracture
dislocations. Closed reduction and maxillomandibular fixation are adequate management
of less complex, minimally displaced maxillary fractures. Maxillomandibular fixation
puts the jaws at rest for the 4 to 6 weeks needed for fracture healing. Maxillary fractures
found to be displaced on CT scans are best managed by means of extended access
approaches that allow direct visualization and by means of anatomic reconstruction of the
buttress system. Maxillomandibular fixation can be accomplished with directly bonded
orthodontic brackets applied before open reduction and fracture-line plating. This method
reduces the risk of arch bar wiring and can reduce operative time (4).
Stable Internal Fixation
Adequate stabilization of fractures through the vertical buttresses can be obtained with
multiple interosseous wires if maxillomandibular fixation is maintained for 4 to 6 weeks.
However, this prolonged period of jaw immobilization can be eliminated if rigid internal
fixation devices (plates and screws) are used to stabilize the maxillary fracture fragments.
Although the term rigid is used to describe the fixation achieved with these implants, it is
somewhat inaccurate when applied to maxillary fractures. Rigidity sufficient to allow
removal of maxillomandibular fixation can be obtained, but it is not sufficient to allow
the patient to return immediately to a normal diet. Fixation devices maintain the position
of the maxillary dentoalveolar complex under the stresses of forces generated by
mastication of very soft foods and deglutition. Internal suspension wires have no useful
role in the stabilization of maxillary fractures and can introduce iatrogenic shortening of
the midfacial vertical dimension. Pediatric facial fractures present unique challenges in
management. A review highlights the relevant points of clinical presentation, treatment,
and the effects of trauma on craniofacial growth (5).
SURGICAL TECHNIQUES
Zygoma
Precise relocation of the displaced zygoma can be greatly simplified if the surgeon
concentrates on reconstruction of the two main external arcs of contour. Restoration of
the horizontal arc reestablishes anterior and lateral projections of the cheek, and
restoration of the vertical arc reestablishes height of malar prominence in relation to the
middle third of the face (Fig. 66.2). The repositioned zygoma can be used as a framework
for repair of associated fractures of the orbital wall. Any form of orbitozygomatic repair
relies heavily on palpation and external visualization of the position of the zygoma and
direct visualization of deep structures through a small incision. Therefore these
procedures are delayed for 5 to 7 days to allow resolution of edema. Preoperative and
intraoperative administration of steroids can reduce the progression of swelling during
surgery and facilitate evaluation of reduction and application of fixation. The repair is not
delayed more than 10 days because the masseter muscle begins to shorten after this time,
making elevation of the zygoma more difficult.
Treatment to attain the multidimensional restoration of the position of the zygoma
becomes increasingly complex as the injury to each arc of contour worsens (Fig. 66.10).
Only patients with absolutely no comminution of any of the projections of the arcs of
contour are treated with limited-exposure reduction techniques, such as the Gillies
operation with or without transzygomatic Steinmann pin fixation. The lateral wall of the
maxillary antrum often is comminuted, even if the other projections of the arcs of contour
sustain simple fractures or separation of a suture line. In these cases, exposure through a
sublabial incision is needed to allow assessment of reduction. Subperiosteal dissection
around the infraorbital nerve to the inferior orbital rim allows evaluation of alignment of
the rim and the anterior wall of the antrum. Displaced fragments of the lateral antral wall
can be repositioned to confirm alignment and bridged with a miniadaptation plate to
stabilize the reconstruction against the downward pull of the masseter muscle (Fig.
66.11). Because the fixation device does not resist heavy occlusal forces, as in a Le Fort
fracture, only two screws into the body of the zygoma above and two screws into the
maxilla below are needed for stability.

FIGURE 66.10. Algorithm for restoration and
stabilization of the position of the malar prominence. OR,
Open reduction; RIF, rigid internal fixation.



FIGURE 66.11. Single-point fixation of an
orbitozygomatic fracture with a miniadaptation plate on
the comminuted lateral antral wall.



An alternative site for placement of a single rigid fixation device for less severe
zygomatic injuries is the reduced zygomaticofrontal suture line. The thickness of the
bone above and below the suture lines makes screw placement easy and gives even
greater stability to the reduction. However, this greater stability is unnecessary in most
cases, and direct visualization of the suture line reduction gives little more information
about the overall position of the zygoma than does direct visualization of the lateral antral
wall. The lateral brow incision needed to expose the suture line can leave a noticeable
scar.
The progression to more complex fractures usually involves comminution of the lateral
antral wall and the medial aspect of the inferior orbital rim as well as displacement at the
zygomaticofrontal suture line. In these cases, accurate realignment necessitates exposure
of the inferior rim through a transconjunctival incision and exposure of the suture line
through either the same incision after detachment of the lateral canthal ligament or
through a separate lateral brow incision. Initial reduction of the zygoma is performed at
the zygomaticofrontal suture line. This reduction is temporarily held in place with a
single wire passed through holes made well away from the thick portion of the rim that
later is used for a rigid fixation implant. Because this temporary wire allows rotational
movement of the zygoma, the position of the malar prominence can be appropriately
adjusted in the lateral and anterior dimensions. This adjustment is accomplished by
means of realigning the orbital rim and lateral antral wall fragments. Resistance to the
pull of the masseter muscle is accomplished with a miniadaptation plate positioned over
the lower end of the zygomaticomaxillary buttress. Additional stability can be obtained
with microadaptation (very low profile) plates placed on the inferior rim and across the
zygomaticofrontal suture line. Thicker plates at these sites can become visible with time
through the thin overlying skin.
If the inferior rim and lateral wall fragments are too small to manipulate or are missing,
traditional three-point reduction usually is inadequate for accurate restoration of the
position of the malar prominence. The prominence typically is displaced posteriorly and
laterally to its normal location. Failure to recognize the amount and direction of
displacement at the time of reduction can leave a flattened cheek and widened face. In
these situations, the fourth point of alignment, the zygomatic arch, must be used to
reposition the point of intersection of the arcs of contour.
If CT scans show that the arch has a single displaced fracture or two greenstick fractures
with bending of the arch, dissection can be carried out over the malar eminence through
the transconjunctival incision to expose the fractures. The fractures are elevated and
realigned. In this step the surgeon must remember that the bone of the middle portion of
the arch is straight and must be reconstructed as such to reestablish both anterior and
lateral projections of the malar prominence (Fig. 66.8A). Although the bone of the arch is
thin, accurate end-to-end realignment usually can be obtained to reconstruct the true
length and contour of the arch. Fixation is applied at the other three points of reduction.
If the arch has a displaced central segment, access to the full length of the horizontal arc
is needed, and a coronal, hemicoronal, or extended pretragal incision is necessary in
addition to the transconjunctival incision. Dissection toward the lateral orbital rim and the
zygomatic arch is in a plane deep to the superficial layer of the deep temporal fascia,
allowing the frontal and orbital branches of the facial nerve to be elevated automatically
with the flap (Fig. 66.12). The periosteum is incised along the orbital rim and along the
arch fragments deep to the attachment of the superficial layer of this fascia. A
subperiosteal dissection is carried over the body of the zygoma to connect with the
subciliary dissection, and all of the components of the zygomatic arch are exposed and
realigned. Fixation with microadaptation plates must be applied to the arch in these cases
in addition to fixation as previously described at the other three points of reduction.

FIGURE 66.12. Completed unilateral frontotemporal
flap needed for the approach to the lateral orbital rim and
entire length of the zygomatic arch. Elevation of the flap
in the correct plane protects all branches of the facial
nerve. In some cases, a full coronal flap offers greater
tissue relaxation and improved exposure of the body of
the zygoma and the zygomatic arch.



If extreme difficulty is encountered in mobilizing the zygoma to its correct position, even
with the extended access approaches, the masseter muscle can be detached from the
zygoma and the arch. This step often is necessary in operations on patients not treated
within the recommended 7 to 10 days. This maneuver does not have long-term effects on
jaw mobility or masticatory function, but the additional soft-tissue trauma and subsequent
scarring can accentuate the prominence of the reconstructed arch, especially if a plate
spans the length of the arch. Accurate draping of the soft tissues over the reconstructed
arch helps to prevent this. Simultaneous upward traction on the skin flap and incised
temporal fascia allows a tight closure that holds the periosteum in correct position over
the arch and zygoma.
Maxilla
Restoration of the pretrauma relations of the tooth-bearing segments of the maxilla to the
mandible and skull base necessitates reestablishment of the proper occlusal relation of the
maxillary and mandibular teeth and stabilization of the midfacial buttress system (Fig.
66.13). If the mandible also is fractured, the lower dental arch must first be stabilized and
accurately related to the skull base; proper alignment of the mandibular condyles in the
glenoid fossae is an absolute requirement. The anteroposterior position of the maxilla can
be set by means of occluding the teeth in stable maxillomandibular fixation. The
midfacial vertical dimension is stabilized by means of reduction and fixation of any
fracture line between the palatoalveolar complex and the base of the skull. When
subcondylar fractures or fractures of the condylar head cannot or should not be managed
with open reduction (Fig. 66.7C), the midfacial buttress system can be reconstructed first
to establish vertical and horizontal positioning of the occlusal plane. Although it may not
restore the relation of the maxilla to the base of the skull with the same accuracy that can
be achieved if it is first related to an intact or totally reconstructed lower arch, this
sequence is the preferred sequence if mandibular vertical ramus height cannot be
accurately restored because of the presence of a condylar injury.

FIGURE 66.13. Management of fractures of the vertical
buttresses.



Although not a part of the maxilla, each zygoma must be accurately repositioned and
stabilized before reattachment of the maxilla to the upper ends of vertical buttresses.
Zygomatic fractures associated with Le Fort fractures of the middle third of the facial
skeleton often necessitate open reduction and internal fixation of the zygomatic arch to
position the zygoma correctly before reattachment of the maxilla. This is particularly
critical if mandibular condylar fractures necessitate reconstruction of the upper jaw first.
Failure to recognize and correct the amount and direction of displacement at the time of
reduction leaves a flattened cheek and widened face and can produce a rotation and
possibly tilting of the maxilla when it is reattached to the malpositioned zygoma.
The integrity of a fractured palate must be reestablished. Palatal fractures, most
commonly parasagittal splits, must be reduced anteriorly at the inferior rim of the
piriform aperture and posteriorly to allow a solid, structurally accurate dentoalveolar
complex to be related to the mandibular teeth. Open reduction and internal fixation of the
anterior extent of a palatal fracture can be accomplished through the same extended
gingivobuccal incision used to expose and repair the vertical buttresses (Fig. 66.14). The
bone above the anterior teeth is more than adequate for placement of a miniadaptation
plate with multiple screws. In some instances, a small amount of bone can be removed
immediately below the anterior nasal spine to facilitate placement of a plate with a flat
contour under the upper lip and base of the columella.

FIGURE 66.14. Exposure of the maxilla through a
midfacial degloving approach. Plate 1 provides fixation
for the anterior aspect of a parasagittal palatal fracture.
Plates marked 2 provide fixation across the fractured
zygomaticomaxillary buttresses and complete triangular
fixation of the palatal fracture. Plates marked 3 were
placed across the frac-tured nasomaxillary buttresses for
inferior repair of a nasoorbitoethmoidal fracture. (From
Stanley RB. Rigid fixation of fractures of the maxillary complex. Facial Plast Surg
1990;7:176, with permission.)



The posterior extent of a palatal fracture usually can be reduced in a closed manner if the
overlying palatal mucoperiosteum is intact. Difficulty manifests as inability to align the
lower end of the zygomaticomaxillary buttress with an accurately reconstructed zygoma
above or the need to overtighten the maxillomandibular fixation wires to pull the lingual
cusp tips of the maxillary molars and premolars into the central fossae of the mandibular
teeth. In these cases, an incision can be made over the posterior extent of the palatal
fracture, and a transosseous wire can be placed across the fracture. This wire does not
serve as a point of rigid fixation of the palatal fracture, but it reduces the fracture gap
posteriorly after it is tightened. Stable fixation is obtained with superficial triangulation
of the palate with plates and screws placed across the anterior extent of the palatal
fracture and across both zygomaticomaxillary buttress areas (Fig. 66.15). Posterior
displacement of a parasagittal palatal fracture can be overlooked easily if parasymphyseal
mandibular fracture is present that has been incompletely reduced at the lingual cortex.
Both dental arches are widened posteriorly, and the maxillary and mandibular teeth can
appear to interdigitate correctly. However, when facial edema resolves, the patient may
notice widening of the intergonial distance.

FIGURE 66.15. Reduction of the posterior gap of a
displaced parasagittal fracture of the palate with a
transosseous wire. Arrows indicate points of triangular
fixation that hold the palatal fracture in reduction (Fig.
66.14).



Palatal fractures exposed by means of laceration of the mucoperiosteum usually are
widely separated and impossible to reduce without a transosseous wire to pull the palatal
shelves together posteriorly. If this method of reduction is not used, but tightening of the
maxillomandibular fixation wires is used to pull the teeth into occlusion, the maxillary
teeth probably are lingually tipped or left in some degree of unilateral or bilateral
posterior crossbite deformity. The exposure through the laceration may be adequate to
allow placement of a plate across the split palate; however, this procedure can be
technically difficult, and these plates frequently become exposed in the mouth and must
be removed.
Acrylic palatal splints are essential adjuncts for stabilization of teeth in a segment of
maxillary bone separated from the palate by an alveolar fracture. Even if a rigid fixation
device cannot be used to attach the isolated alveolar segment to the surrounding
maxillary bone, the combination of a sturdy buccal arch bar, a palatal splint, and
circumdental wires to cinch the involved teeth between the bar and the splint usually
provides enough stability to allow removal of the maxillomandibular fixation.
Only after the zygomatic and palatal fractures have been repaired can the maxillary
complex be reattached superiorly. Reattachment begins with the zygomaticomaxillary
buttress that has the less severe injury. Unlike the anterior wall of the maxilla, which
often is severely comminuted, the zygomaticomaxillary buttress often is traversed by a
single fracture line that can be easily reduced, or it has a single free-floating fragment that
can be accurately related to the zygoma above and the lower maxilla below. At least one
zygomaticomaxillary buttress usually can be reduced in this way to set the correct
vertical dimension of the middle third of the face. After stabilization of this buttress,
reduction and fixation of the other zygomaticomaxillary buttress and the nasomaxillary
buttresses can proceed. If both zygomaticomaxillary buttresses are severely comminuted,
reconstruction of the nasomaxillary buttresses can facilitate reestablishment of the
vertical dimension. In most cases of comminution of the zygomaticomaxillary struts,
however, the nasomaxillary buttresses are even more fragmented and difficult to realign.
Stability of the reattachment of the maxillary complex is gained mainly through
reconstruction of the zygomaticomaxillary buttresses. Reconstruction of the
nasomaxillary buttresses can provide some supplementary vertical stability to the overall
reconstruction, but only if the upper confluence of these struts (nasoorbitoethmoidal
complex) is intact. If plates and screws are used for fixation and the patient is allowed to
function early, a delicate nasoorbitoethmoidal repair cannot be relied on to transmit
occlusal forces to the base of the skull. Instead, zygomaticomaxillary buttress
reconstruction must be used to hold the repositioned maxilla in place during healing.
Plates must be positioned to overlie the zygomaticomaxillary buttresses as closely as
possible, and three screws are used to anchor the plate to the zygoma above and the
maxilla below. Placement of screws into the lower end of a plate or a bone graft can be
difficult if the fracture line closely parallels the apices of the molar and premolar teeth.
This problem usually can be overcome with L-shaped plates that allow placement of
more screws close to but not through the root tips (Fig. 66.14).
Comminution of the lower ends of the vertical buttresses severe enough to mandate bone
grafting for adequate stabilization is uncommon, although occasional cases occur in
which gaps of 1 to 2 cm of severely comminuted or absent bone exist in one or both
lateral antral walls. Onlay split cranial bone grafts are attached across these gaps. The
grafts can be contoured and positioned to allow placement of lag screws that do not
damage the root tips. Reconstruction of the vertical dimension cannot be done with the
same precision for these patients as for those who undergo successful edge-to-edge
approximation of in situ fracture fragments.
Orbital Walls
Reconstruction of the orbital walls can begin only after total reconstruction of the
zygoma and any other injuries of the horizontal and vertical buttress system. This
includes an accurate anatomic reconstruction of the frontal bar, to the lateral ends of
which the orbitozygomatic complexes are reattached. During repair of fractures of the
roof of the orbit, the surgeon must be aware of an essential difference in positioning of
bone fragments or bone grafts during the repair. Although the goal of reconstruction of
the lateral, inferior, and medial walls of the orbit is an exact reconstruction of contour and
position, the goal of reconstruction of the roof is to position it higher than its pretrauma
level. The normal upward convexity of the roof is difficult to duplicate. A reconstructed
roof that appears to be at the correct level often is too flat and pushes the globe inferiorly.
This problem is avoided if the rebuilt roof is attached to the frontal bar at a level
approximating the normal height of convexity of the roof and not the level of its normal
junction with the frontal bar (Fig. 66.16).

FIGURE 66.16. A: Upwardly convex configuration of
the orbital roof above a normally positioned globe. B:
Flat bone graft attached to the lower edge of the superior
orbital rim has displaced the globe inferiorly. C: Similar
graft attached at a higher point on the frontal bar has not
displaced the globe.



The zygomatic contribution to the lateral orbital wall most often remains attached to the
body of the zygoma and is correctly rearticulated to the greater wing of the sphenoid
bone with reconstruction of the zygoma. In some cases, reduction of this suture line can
be used as an indicator of adequacy of the overall realignment of a displaced zygoma.
However, the serrated edge of this projection of the zygoma frequently is comminuted,
and realignment of the suture line cannot be relied on as a main indicator. In the unlikely
event of a displaced sphenoid wing fracture, the lateral wall component of the zygoma
can be used as a landmark for repositioning the orbital plate of the sphenoid bone. Only
rarely is an alloplastic or autogenous graft needed to reconstruct a lateral wall defect to
correct herniation of orbital soft tissues into the temporal and infratemporal fossae.
However, if a high-impact injury does produce comminution and displacement of the
lateral orbital wall, a split calvarial graft is the ideal choice of graft material. Because a
lateral approach must be used to expose these retrobulbar bone injuries safely, the
calvarial donor site is already in the surgical field. A fairly flat area of skull usually can
produce a graft that closely matches the contour of the lateral orbital wall. The inserted
graft can be stabilized to the frontal bone or the zygoma with a microplate and screws.
The orbital floor projection of the zygoma usually also remains intact and is restored to a
normal position after the zygoma is repositioned. The medial floor (orbital plate of the
maxilla) can be reconstructed with the intact lateral floor as a stable landmark.
Reconstruction of a defect involving only the concave anterior aspect of the floor usually
can be accomplished with an alloplastic implant. Dissection of the floor must expose the
entire circumference of the defect so that an almost 360-degree ledge is formed to support
the implant. Of the various alloplasts available, polypropylene mesh has many properties
that make it an ideal choice. It is readily available, is easily trimmed, and can be layered
to strengthen the reconstruction. Clotted blood and fibrous tissue eventually fill the mesh
to prevent implant migration, obviating fixation of the implant to the orbital rim or
residual floor.
Reconstruction of defects of the concave anterior and convex posterior floor requires an
implant with rigidity greater than that of polypropylene because there often is no ledge of
residual floor to stabilize the implant posteriorly or medially, even when the orbital floor
dissection is carried well into the posterior third of the orbit. A stiffer alloplastic material
that is well suited for larger defects that have medial and lateral ledges for support is
porous high-density polyethylene. This material, which has the same favorable properties
as polypropylene mesh, does not require full 360-degree support to remain in place. For
defects that extend to the junction of the floor and lamina papyracea, a graft with even
more rigidity is needed to overcome the lack of posterior and medial support of the
implant. Outer-table calvarial bone is ideally suited for reconstruction of these larger
defects. This bone is easily harvested and contoured to match most large defects in the
floor, and its rigidity eliminates the need for medial and posterior support. The graft can
be stabilized by means of attaching it to the orbital floor projection of the zygoma with
one or two lag screws or to the reconstructed orbital rim with miniplates and screws in a
cantilevered manner (Fig. 66.17A). The calvarial bone graft cannot restore an accurate
position of the globe if the surgeon is hesitant in floor dissection and does not venture the
sometimes necessary 35 to 40 mm into the posterior third of the orbit to allow maximal
reconstruction of the convex posterior floor (Fig. 66.3).

FIGURE 66.17. A: Reconstruction of a large defect of
the entire orbital floor medial to the infraorbital nerve. An
outer-table cranial bone graft is cantilevered from the
inferior rim with a miniadaptation plate. B: A second
graft is attached to the floor graft with microplates to
reconstruct a defect that involves the floor and medial
wall of the orbit. The preassembled bone grafts are
inserted through the transconjunctival incision and
manipulated into position through a medial orbital or coronal incision.



Reconstruction of defects that involve the concave anterior floor, convex posterior floor,
and medial orbital wall (lamina papyracea) offers the greatest challenge. Although these
severe orbital injuries usually are part of a panfacial fracture, they can occur with isolated
orbitozygomatic injuries. Complete exposure of the medial wall of the orbit is mandatory
and is best accomplished through a coronal incision.
Reconstruction is made difficult by the need to restore the integrity of walls themselves
and the exact relation of the medial wall to the floor. Cranial bone grafts cannot be bent
without fracturing, but they can be joined together with microplates to reproduce a
correct medial wall-to-floor relation (Fig. 66.17B). An alternative is to use prefabricated
titanium orbital floor plates with medial and lateral wings that act as a cradle for bone
implants and greatly facilitate placement and stabilization. However, insertion of these
plates puts a large amount of metal in contact with the maxillary and ethmoidal sinuses,
and problems with chronic infection become a consideration.
COMPLICATIONS
The complications of malocclusion and facial asymmetry that can be caused by lack of
recognition and management of midfacial skeletal injures have been discussed. Other
serious occurrences include various iatrogenic complications introduced by the surgical
intervention itself.
Lid Damage
Even the most experienced surgeon occasionally notices increased scleral show or even
gross ectropion after any incision that violates the lower eyelid to approach the orbit. A
transconjunctival incision greatly reduces this risk, and with the addition of lateral
cantholysis approximately 2 mm medial to the lateral canthus, even the medialmost
aspect of the inferior rim and medial wall of the orbit can be exposed. The cornea can be
adequately protected during dissection of the deep orbit and placement of large alloplastic
or autogenous grafts with traction sutures that pull the bulbar conjunctiva over the globe
(Fig. 66.18).

FIGURE 66.18. Transconjunctival incision with
cantholysis of lower tarsal plate attachment to lateral
canthal ligament. Traction sutures are used to pull the
conjunctiva superiorly to protect the cornea. The orbital
rim is exposed through an incision 2 to 3 mm below the
junction of the orbital septum and rim periosteum.



Iatrogenic lid damage can be lessened with careful dissection that adds no injury to the
orbicularis muscle or the orbital septum. The periosteum overlying the inferior orbital rim
is not incised immediately over the crest of the rim but on the downward slope of the rim
2 to 3 mm anterior to the crest. If the rim is comminuted and the fragments are depressed,
correct placement of the periosteal incision is difficult and the risk of damage to the
orbital septum increases. Reduction of the fragments to a more anatomic position through
a sublabial incision before incision of the rim periosteum reduces the risk. The rim
incision is not sutured during closure of the lid to reduce the risk of tethering the orbital
septum to the reconstructed rim. The conjunctival incision is closed with continuous 6-0
fast-absorbing catgut suture, and the tarsal plate is reattached to the inferior limb of the
lateral canthal ligament with buried 4-0 polyglactin 910 suture. The lid margin is
precisely approximated with 6-0 silk suture, which remains in place for 7 days. A Frost
suture between the upper and lower eyelids offers no additional protection against lower
lid retraction if the transconjunctival opening and closure are correctly performed. If the
soft tissues over the inferior orbital rim, malar prominence, and anterior maxillary wall
have been completely elevated during reconstruction, absorbable suspension sutures can
be placed from the periosteum of the cheek tissues to the reconstructed rim. This
maneuver helps to maintain the length of the lower lid as the infraorbital soft tissues
redrape over the reconstructed inferior orbital rim.
Lip Distortion
A subtle but disturbing deformity can be caused by use of the sublabial approach to
maxillary fractures. This deformity includes hollowing of the soft-tissue contours over
the canine fossa area and superior deviation of the corner of the mouth and lateral aspect
of the upper lip. It is caused by collapse and contraction of the buccal soft tissues into
large anterior and anterolateral antral wall defects. Although the exact size of the defect
necessary to cause this is unknown, defects of greater than 1.0 cm
2
are considered for
overlay bone grafting.
Vision Loss
Damage to the globe or the optic nerve with resultant loss of vision is a risk of any
surgical procedure within the orbit. In some instances ocular injury from the trauma itself
can prevent management of the fractures if manipulation of the globe is likely to worsen
the ocular injury and precipitate total loss of vision in the eye. If the fractured orbit
houses the patient's only seeing eye, reconstruction is limited to returning the globe to
functional position if the orbit is severely disrupted and marked displacement of the globe
has occurred. Bone grafting is directed at providing basic support for the globe and not at
total reconstruction of the orbital volume and shape. Intraoperative tonometry and
funduscopic examination are considered in these and all other cases in which large
implants are placed into the posterior orbit. Forward positioning of the globe by an
oversized implant occasionally causes an acute increase in intraocular pressure, and the
implant must be removed and reduced in size.
Implant Visibility
Miniplates and screws along the lateral orbital rim and zygomatic arch usually are
visually undetectable if low-profile titanium or cobalt-chromium alloy plates with screws
1.3 mm or less diameter are used. These fixation devices can be left in place permanently.
Because a plate positioned on the inferior rim can produce an irregular contour visible
through the thin skin of the lower eyelid, it is preferable not to use rigid fixation devices
on the inferior orbital rim unless absolutely necessary for stability of the reconstruction.
If such a plate is placed and is visible after healing is complete, a second surgical
violation of this lower lid to remove the plate does expose the patient to a higher risk for
lid complication.
Malocclusion
Rigid fixation is an unforgiving technique that produces serious occlusal disturbances if
used inappropriately to manage fractures of tooth-bearing segments. If the plates are not
correctly adapted to the bone, tightening of the screws can produce torque in the system,
and the fragments can move so that malocclusion is produced when the
maxillomandibular fixation is removed. This is less likely to occur now that thinner, more
malleable titanium or cobalt-chromium alloy plates are being used rather than the stiffer,
harder to bend stainless steel plates.
The surgeon must consider the risk of inaccurate condylar seating in the glenoid fossae in
all cases involving tooth-bearing segments of bone. Patients with complex maxillary
injuries can have a deranged occlusal relation that is difficult to correct and prevents the
teeth from interdigitating in a passive manner before application of maxillomandibular
fixation. One or both mandibular condylar heads invariably are displaced from their
normal centric occlusion position in the glenoid fossae if the maxillomandibular fixation
is used to pull the patient into occlusion. Even if the plates are subsequently accurately
adapted to the repositioned maxillary fragments, malocclusion develops after
maxillomandibular fixation is removed and the patient's normal muscle balances return
the mandible to its correct position. If gross malocclusion does not result and the patient
learns to function in this altered position, chronic joint discomfort is likely to develop.
An altered relation within the temporomandibular joint can be a problem for patients who
have associated mandibular injuries. Edema, effusion, or hematoma can exist within the
joint structures and displace the condylar head to an abnormal position. This produces a
risky situation for rigid fixation on the maxillary fractures. If there is doubt about the
position of the condylar heads within the glenoid fossae, plates and screws can be used
for rigid fixation of any associated Le Fort III or zygomatic fractures, and wire
osteosynthesis can be used for the Le Fort I and II components. Although the patient must
endure maxillomandibular fixation for 4 to 6 weeks, the semirigid wire fixation at the
maxillary level of the buttresses allows the patient to adjust the relation of the
maxillomandibular complex to the base of the skull during the early postsurgical period.
If rigid fixation is used and an error in postoperative occlusion is discovered, the patient
must be returned to the operating room for revision surgery. Reapplication of
maxillomandibular fixation to allow the patient's muscles or orthodontic traction bands to
pull on misaligned fragments is uniformly unsuccessful because of the rigidity of the
fixation devices.
BIORESORBABLE IMPLANTS
Fixation implants ultimately are fabricated from bioresorbable materials that can be
contoured, remain rigid during fracture healing, resorb in a reasonable time (6), and leave
no permanent evidence of their presence. Polyglycolic acid implants have been used to
treat humans, but the rate of resorption has been erratic. In some cases, implant
breakdown products have initiated an intense inflammatory response with subsequent
fibrosis. For the immediate future, metallic implants remain the best rigid fixation devices
for the management of orbitozygomaticomaxillary fractures.
THREE-DIMENSIONAL COMPUTED TOMOGRAPHIC
RECONSTRUCTIONS
Although most information necessary to evaluate orbitozygomaticomaxillary fractures
can be seen on standard axial and coronal CT scans, three-dimensional reconstructions
can help surgeons better conceptualize the overall injury. Precise calculation of changes
in orbital volume and the amount of displacement of superficial bony landmarks is
possible with three-dimensional images. This is particularly valuable for patients who
cannot be positioned for true coronal CT for optimal evaluation of the orbital walls.
However, coronal reformations generated from fine-cut axial CT scans are less expensive
and more readily obtained than three-dimensional reconstructions. Although they do not
supply the same detail in equal clarity, the coronal reformations usually supply adequate
information for orbital wall evaluation. Perhaps more important, technical limitations
placed on surgery on the craniofacial skeleton by surrounding soft-tissue structures
probably always prevent the surgeon from full use of the additional information gained
from multidimensional imaging. Stereoscopic three-dimensional CT images are useful in
evaluating facial fractures. These are made when an image in a pair is different from its
mate by a 6-degree shift of the z-axis (7).
INTRAOPERATIVE COMPUTED TOMOGRAPHIC SCANNING
Portable CT scanners allow immediate evaluation of fracture reduction in the operating
room. The quality of these scans appears sufficient to allow evaluation of relocation of
the malar prominence on axial scans and realignment of the orbital walls on coronal
reformations. The expense of the scanner and technologist time can be offset by
elimination of the need for extended access approaches to evaluate reduction of each
fracture line, thus decreasing operating room time and expense. Intraoperative CT to
confirm alignment of unexposed fractures can increase the feasibility of endoscopic
management of selected orbitozygomaticomaxillary fractures.

HIGHLIGHTS
Fractures involving the skeleton of the middle third of the face
cannot be evaluated and managed in a segmental manner. They
are approached as orbitozygomaticomaxillary fractures.
Return to normal masticatory function and facial appearance
after orbitozygomaticomaxillary fractures necessitates total
anatomic restoration of the skeletal unit that maintains the
position of the tooth-bearing segments of alveolar bone and the
critical soft-tissue structures occupying the middle third of the
face.
Posttraumatic evaluation of midfacial injuries must include CT
evaluation of the horizontal and vertical buttress system, the
external arcs of contour of the zygoma, the orbital walls, and
the mandibular condyles.
Visual acuity must be documented in both eyes before
reconstructive orbital surgery. Ocular injuries can delay or
contraindicate reconstruction of the involved orbit. If the patient
has only one seeing eye, reconstruction of the orbit housing this
eye is directed at returning the eye to a functional position.
Total construction of the orbit is contraindicated if extensive
posterior orbital dissection or forceful retraction of the globe is
necessary for placement of large alloplastic or autogenous
grafts.
The zygomatic arch can be used as a fourth point of reduction
during repair of orbitozygomatic fractures due to high-velocity
impacts that have caused severe comminution of the inferior
orbital rim and lateral antral wall. Total reconstruction of the
arch, in particular its straight central portion, gives the most
accurate anterior repositioning of the malar prominence.
Orbital reconstruction must return the lateral wall, floor, and
medial wall to their normal positions. Because its normal
upward convexity is difficult to recreate, a reconstructed orbital
roof is reattached to the frontal bar of the cranium at a level
approximating the highest convexity of the orbital roof, not at
the level of the orbital rim. If this is not done, the globe usually
is depressed by the flat reconstruction.
The most common error in orbital reconstruction is failure to
repair the convex posterior orbital floor and its gradual slope
into the medial orbital wall. This area is behind the globe, and
the dissection needed for reconstruction can extend 35 to 40
mm posterior to the orbital rim.
The most accurate reconstruction of the vertical dimension of
the middle third of the face is achieved with open reduction of
the vertical buttresses if fracture dislocations are seen on CT
scans. Loss of vertical dimension is more likely to be caused by
use of internal suspension (circumzygomatic or craniofacial)
than by Le Fort fractures themselves.
The occlusal relation of the maxillary and mandibular teeth
must be reestablished in treating patients with fractures of the
tooth-bearing segments of the maxilla. Maxillomandibular
fixation, however, does not automatically restore the correct
relation of the palatoalveolar complex to the base of the skull if
one or both mandibular condyles are incorrectly seated in the
glenoid fossae. Displacement of a condyle from the centric
occlusion position that it normally occupies during maximal
interdigitation of the teeth can be caused by trauma to the joint
structures themselves or by overzealous use of the fixation
wires to pull the patient into occlusion.
Rigid (plate and screw) fixation is an acceptable alternative
therapy for fractures that separate the maxillary complex from
the midfacial skeleton. Rigid fixation allows immediate
removal of maxillomandibular fixation and early, limited
function. However, the procedure is much more technique
sensitive than is closed or open reduction with interosseous
wire fixation. Errors produce an unacceptably high rate of
iatrogenic complications that necessitate revision surgery.
Malocclusion is the most common complication and usually is
related to problems with condylar positioning. In these cases,
the maxilla is left in an abnormal position when the
maxillomandibular fixation is removed and the displaced
condyle or condyles return to a position that is closer to normal.
CHAPTER REFERENCES
1. Touma BJ, Ramadan HH, Bringman JJ, et al. Maxillofacial injuries caused by all-terrain vehicle
accidents. Otolaryngol Head Neck Surg 1999;121:736739.
2. Manson PN, Grivas A, Rosenbaum A, et al. Studies on enophthalmos, II: the measurement of
orbital injuries and their treatment by quantitative computed tomography. Plast Reconstr Surg
1986;72:203214.
3. Parsons GS, Mathog RH. Orbital wall and volume relationships. Arch Otolaryngol Head Neck
Surg 1988;114:743747.
4. Utley DS, Utley JD, Koch J, et al. Direct bonded orthodontic brackets for maxillomandibular
fixation. Laryngoscope 1998;108:13381345.
5. Winzenberg SM, Imola MJ. Internal fixation in pediatric maxillofacial fractures. Facial Plast Surg
1998;14:4558.
6. Eppley BL. Use of a resorbable fixation technique for maxillary fractures. J Craniofac Surg
1998;9:317321.
7. Seno H, Mizunuma M, Nishida M, et al. 3D-CT stereoscopic imaging in maxillofacial surgery. J
Comput Assist Tomogr 1999;23:276279.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

67 FRACTURES OF THE NASAL AND FRONTAL SINUSES
Head & Neck SurgeryOtolaryngology
67




FRACTURES OF THE NASAL AND FRONTAL
SINUSES
BYRON J. BAILEY
LUKE K. S. TAN

B.J. Bailey and L.K. S. Tan: Department of OtolaryngologyHead and Neck Surgery, University of Texas
Medical Branch at Galveston, Galveston, Texas.


Nasal Fractures
Basic Anatomy
Pathophysiology
Diagnostic Assessment
Treatment
Nasal Fractures in Children
Nasofrontal-Ethmoidal Fractures
Nasoethmoidal Orbital Fractures
Emergencies
Frontiers of Knowledge
Fractures of the Frontal Sinus
Epidemiology and Etiology
Anatomy
Biomechanics of Frontal Sinus Fracture
Evaluation
Radiologic Evaluation
Antibiotic Prophylaxis
Historical Overview of Frontal Sinus Surgery
Treatment
Frontonasal Drainage
Complications
Chapter References
NASAL FRACTURES
Because of its prominent position and protruding, delicate skeleton, the nose is
predisposed to soft-tissue injury and fracture. Nasal fractures rank third in incidence,
behind fractures of the clavicle and the wrist. Many fractures of the nasal bones and
septal skeleton go unrecognized and unmanaged at the time of the initial injury, but they
account for a high percentage of the septoplasty procedures performed later for nasal
obstruction or deviation.
With proper assessment and management, most nasal fractures can be restored to proper
alignment, and complications such as cosmetic deformity, nasal valve dysfunction, and
airway obstruction can be prevented. Closed or open reduction is easier within 2 weeks of
the fracture than it is later, when more complex and less reliable reconstructive
techniques must be used.
All severe blows to the nose should be expected to have caused nasal fracture. If there is
a history of epistaxis with the injury, the index of suspicion must be very high. The
burden of proof is on the examining physician to rule out serious bony or cartilaginous
fractures. This chapter explains the rationale for early closed reduction for simple
depressed fractures of the nasal bones, fracture-dislocation of the septum, and fractures of
the nasal pyramid with bridge deviation that is less than one half the width of the nasal
bridge. Open reduction is indicated for fractures with nasal deviation greater than one
half the width of the nasal bridge, for fractures with extensive fracture-dislocation of the
septum, and in instances in which it is impossible to achieve optimal reduction with
closed reduction.
Basic Anatomy
Nasal anatomy underlies the types of injury. Nasal skin is thin and loosely adherent over
the upper two thirds of the nose. It is thicker and tightly adherent over the lower third,
where sebaceous glands are abundant. The skin is thinner among women and girls and
among the young. Nasal skin has an excellent blood supply and usually heals rapidly with
minimal scarring. The sensory innervation of the nose and adjacent face is supplied by
the supratrochlear, infratrochlear, anterior ethmoidal, and infraorbital nerves Fig. 67.1.

FIGURE 67.1. A: Nasal arterial blood supply. B: Nasal
innervation and skin.



The bone structure of the nasal pyramid comprises the two rectangular nasal bones and
the frontal process of the maxilla. The nasal bones are thick and rigid at their superior
articulation with the frontal bone and thin at their inferior articulation with the upper
lateral cartilage. Most fractures occur in the lower half of the nasal bones.
The cartilages of the external nose are complex and more important than is the bony
skeleton in terms of appearance, function, and injury. The upper lateral cartilages are
curved, triangular structures with bases that articulate in the midline. The upper lateral
cartilages also articulate with the undersurface of the nasal bones superiorly, at which
point they are particularly vulnerable to dislocation from the nasal bones. The upper
cartilages are critical in defining nasal appearance according to size, shape, position, and
symmetry. The upper lateral cartilages also have important articulations with the
quadrangular cartilages of the septum and with the lower lateral or alar cartilages. This
articulation between the upper and lower lateral cartilages is a complex fibrous joint that
also functions as the nasal valve, a critical region that modulates the flow of inspired air.
The paired lower lateral cartilages are gull-shaped with lateral segments that expand as
they curve superiorly and laterally. The medial crus of each lower cartilage has a fibrous
articulation with the caudal margin of the quadrangular cartilage of the septum. The
lower cartilage supports the tip and defines tip contour and the shape and size of the
nostrils. The sesamoid cartilages lie in the fat pad between the lower cartilages and the
margin of the piriform aperture of the maxilla. They vary in size, shape, and number and
are less important than the cartilages described previously. Figure 67.2 shows the external
nasal skeleton.

FIGURE 67.2. External nasal skeleton. A: Frontal view.
B: Oblique view.



The nasal septum comprises the vomer bone inferiorly, the perpendicular plate of the
ethmoid bone posteriorly, and the quadrangular cartilage anteriorly. The septum is lined
with mucoperiosteal and mucoperichondrial soft tissue that is easily torn when septal
fracture-dislocation occurs.
Two regions of the quadrangular cartilage are important in nasal injury. In the inferior
aspect, the fibrous articulation of the caudal margin of the quadrangular cartilage can be
disrupted and displaced, the cartilaginous margin being displaced to one side. In the
superior aspect, a C-shaped fracture can occur and involve the bony and cartilaginous
septum. The edges of this fracture can become interlocked and hold the displaced nasal
bone fragments in a laterally displaced position.
Because of the anatomic architecture of the nose, the upper third is rigid and static, and
the lower two thirds are dynamic and mobile. Lateral force can fracture the nasal spine of
the maxilla, an anterior projection that articulates with the quadrangular cartilage and the
medial crura of the alar cartilages. If the nasal spine heals in a laterally displaced
position, considerable deformity can occur.
Pathophysiology
An inadequate understanding of the pathophysiologic mechanism of nasal trauma is
responsible for the high failure rate of management. The injury caused by a blow to the
nose varies with the following factors (1): (a) the patient's age (tissue flexibility), (b) the
amount of force applied, (c) the direction of the force, and (d) the nature of the striking
object. Common soft-tissue injuries include lacerations, ecchymosis, and hematoma of
the external or internal nose. Skeletal injuries comprise fractures (comminution is more
common among older patients), dislocations (more common among children), and
fracture-dislocations. Dislocation injuries can involve any articulation of the external
nasal skeleton or the septum Fig. 67.3. One epidemiologic study indicates that the nasal
bones are more vulnerable to fracture after rhinoplasty. This is an especially important
issue for athletes who are considering rhinoplasty (2).

FIGURE 67.3. A: Septal dislocation. B: Septal fracture
patterns.



Nasal fractures can be open, closed, or both. Nasal fractures sustained in urban areas
usually occur in fights, auto accidents, or sports. In rural areas, nasal fractures occur in
farm or work accidents, sports, or leisure activities. Injuries incurred in automobile
accidents usually are the most serious. Although lap belts save lives, they often set the
stage for severe nasal fractures (extreme comminution or nasoethmoidal complex
injuries).
The pattern of nasal fractures varies with the direction of applied forces; there is a distinct
difference between frontal and lateral forces (3). A force of 25 to 75 pounds per square
inch is needed to produce a nasal fracture. If the force is applied from a frontal direction,
the injury varies from minor (lower margin of nasal bones) to marked (flattening of the
external skeleton). These injuries are classified according to depth as frontal planes 1, 2,
or 3 Fig. 67.4. Plane 2 and 3 fractures also can involve the septum.

FIGURE 67.4. Nasal fractures according to frontal plane
depth. A: Normal. B: Plane 1. C: Plane 2. D: Plane 3.



Lateral forces can cause only a depressed fracture of the ipsilateral nasal bone or can be
strong enough to outfracture the contralateral nasal bone as well. Septal fractures that
twist or buckle the nose can produce interlocked fragments that cannot be reduced with
closed techniques. Cartilaginous attachments to the nasal bones or maxilla can be
separated. The result is marked instability of the external framework and deformity that
obstructs the nasal airway. The concept of lateral planes is shown in Fig. 67.5. Septal
fracture lines usually are vertical when they are located anteriorly and horizontal when
located posteriorly. Septal fractures are said to activate interlocked stresses, and during
the process of healing by fibrosis, they can produce septal twisting of various
configurations (C-shaped, S-shaped, or spurs). Examples of the most common types of
nasal bone fractures are illustrated in Fig. 67.6.

FIGURE 67.5. Lateral force injuries with displacement.
A: Normal. B: Mild. C: Moderate. D: Severe.



FIGURE 67.6. Nasal fractures. A: Unilateral. B:
Bilateral. C: Open book. D: Comminuted. E: Posterior-
inferior impaction. F: Medial canthal ligament avulsion.



Colton and Beekhuis (1) described a third class of fractures, those produced by force
applied from below. They emphasized that these forces are most likely to produce septal
fractures and dislocations, particularly dislocation of the quadrangular cartilage from the
crest of the maxilla Fig. 67.7. This injury can cause telescoping of fragments and
shortening of the nose or blockage of one side of the nasal airway. Colton and Beekhuis
(1) conducted a careful analysis of fracture patterns after application of frontal or lateral
forces of 8 to 350 kPa. Fractures were made in fresh cadavers with frontal and lateral
forces, and three typical fracture patterns were produced Fig. 67.8. These findings of
cadaver studies correlated closely with observations of a large series of patients who
underwent open reduction procedures. The authors concluded that open reduction is
indicated whenever deviation of the nasal pyramid exceeds one half the width of the nasal
bridge.

FIGURE 67.7. A: Fracture patterns with force applied
from below. B: Dislocation of septum with fracturing
lateral force.



FIGURE 67.8. Patterns of frontal and lateral force
fractures. A: Greater frontal force. B: Intermediate frontal
force. C: Lesser frontal force.



Diagnostic Assessment
A history of substantial trauma to the nose suggests the possibility of a nasal fracture, and
further evaluation is mandated Table 67.1. When epistaxis has occurred, the probability
of open fracture is high. When the patient also reports a change in nasal appearance or the
onset of nasal airway obstruction, nasal fracture is almost certainly present. The history
interview includes questions about the force, direction, and nature of the impact.

TABLE 67.1. DIAGNOSIS NASAL
FRACTURES



Physical examination is the most important part of diagnosis. Many patients
underestimate the seriousness of the injury and do not seek medical attention. Surveys
have shown that about one half of patients examined in local general medical clinics and
emergency departments do not undergo intranasal assessment. Edema can obscure
injuries of the nasal pyramid.
The nose must be inspected externally and internally to rule out deformity, deviation, or
abnormal contour. Lacerations, mucosal tears, ecchymosis, and hematoma strongly
suggest a fracture. Other signs of nasal fracture include lid edema, scleral chemosis,
periorbital ecchymosis, and subconjunctival hemorrhage. Subcutaneous emphysema can
be present owing to attempts by the patient to blow clots from the nose. Intranasal
examination is preceded by mucosal decongestion and careful removal of clotted blood.
Palpation is performed systematically to assess tenderness and stability. Evidence of
nasal bone depression, displacement, or mobility confirms the diagnosis of fracture in
most instances. It can be helpful to place a nasal fracture elevator inside the nose and a
fingertip on the outside to check for nasal bone mobility. Results of a too-gentle
examination can be misleading in the presence of edema and tenderness. Nasal and septal
cartilages are checked for possible dislocation from the fibrous attachments. Special
attention is paid to the lateral cartilages, the nasal valve, and the quadrangular cartilage.
The tip of the nose is pushed toward the occiput to check for integrity of septal support.
Tenderness with bidigital palpation and lateral force on the maxillary spine strongly
suggests serious septal injury. False motion, mobility, crepitus, and bony angulation are
the hallmarks of fracture.
Radiographic studies can be either helpful or confusing. They can reveal details of the
fracture Fig. 67.9. They also can be misleading because of suture lines, vascular
markings, or previous fractures. They are normal for 47% of patients with fractures.
Some authors recommend the use of dental radiographic film held at the side of the nose
and parallel to the sagittal plane with exposure of the film from the side. The bony
septum, dorsal pyramid, and lateral nasal walls can be evaluated on the Waters view. For
some patients, the nasal bones can be seen with an occlusal view or with the use of a soft-
technique lateral radiograph. Results of clinical studies have shown that nasal radiographs
are not helpful in diagnosing or managing nasal fractures. Many surgeons have concluded
that the time and expense of radiographic studies cannot be justified on the basis of
clinical necessity (4). Photographic documentation is recommended and can serve as an
important part of the record along with the radiographs. Clinicians need to obtain
preinjury photographs for their records when possible, because 30% of patients have
previous nasal deformities.

FIGURE 67.9. Radiograph shows nasal fracture.



The physician looks for common associated injuries such as dental fractures, ocular
trauma, involvement of the lacrimal system, and cerebrospinal fluid (CSF) fistula.
Cerebrospinal fluid leaks may not appear for several days after injury, but suspicion runs
quite high if the patient has anosmia. This finding strongly suggests the possibility of
fracture of the cribriform plate (1).
An important ongoing task is education of the emergency department staff and local
primary care physicians. Awareness of the signs, symptoms, and importance of nasal
fractures is essential to early diagnosis, early treatment, and avoidance of late
complications. Because of the present medicolegal climate, the policy of management of
nasal fractures by nonspecialists is being discouraged. There is a relatively high incidence
of patient dissatisfaction with the outcome of treatment in terms of the appearance and
function of the nose.
Treatment
General
The treatment options are closed or open reduction of the fractured external pyramid or
septum. The best opportunity for successful management is during the first 3 hours after
injury (1). If this is impossible, most authors agree that reduction is performed within 3 to
7 days. Colton and Beekhuis (1) stated that there is no harm in waiting until swelling has
diminished and surgery is convenient for the patient and surgeon.
The indications for closed reduction are (a) unilateral or bilateral fracture of the nasal
bones and (b) fracture of the nasal-septal complex with nasal deviation less than one half
the width of the nasal bridge. Open reduction is generally recommended for (a) extensive
fracture-dislocation of the nasal bones and septum, (b) nasal pyramid deviation exceeding
one half the width of the bridge of the nose, (c) fracture-dislocation of the caudal septum,
(d) open septal fractures, and (e) persistent deformity after closed reduction. Other
indications for open reduction include septal hematoma, inadequate bony reduction due
to septal deformity, combined deformities of septal and alar cartilages, displaced
fractures of the anterior nasal spine, and history of recent intranasal surgery.
Essential ingredients for proper management include adequate anesthesia, proper light
and suction, appropriate instruments, and suitable splinting material. Informed consent
must include a discussion of optional management strategies, explanation of operative
risks, including the possibility of persistent deformity, and for children the risk that the
injury or surgery will disturb normal nasal growth and development Table 67.2.

TABLE 67.2. TREATMENT GOALS



Closed Reduction
Anesthesia
The nose is anesthetized with 2% lidocaine with epinephrine as an intranasal spray. Four
cotton pledgets are placed inside the nose Fig. 67.10. Mathog recommends using 0.25%
phenylephrine and Cetacaine as the first application and adding five drops of 1:10,000
epinephrine to the 4% cocaine used on the cotton pledgets. He reminds us that no more
than 8 mL of 4% cocaine is used. Topical anesthesia is supplemented with injection of
2% lidocaine with 1:100,000 epinephrine along the dorsum of the nose lateral to the nasal
pyramid and at the base of the anterior septum Fig. 67.11. These injections block the pain
fibers in the infratrochlear, infraorbital, greater palatine, and superior alveolar nerves.
The physician allows 15 to 20 minutes for anesthesia to become effective. Giving 5 to 10
mg of diazepam about 30 minutes before surgery helps sedation. For more extensive
procedures, intravenous sedation provides adequate anesthesia in most instances (5).

FIGURE 67.10. Cotton pledgets placed in nose for
anesthesia (multiple views). 1, Roof of nose; 2,
midportion, lateral nasal wall; 3, floor of nose; 4,
midportion, septal mucosa.



FIGURE 67.11. Lidocaine injection for anesthesia.



Some authors have proposed an alternative form of anesthesia for reduction of simple
nasal fractures. An eutectic mixture of local anesthetics (EMLA cream) is prepared. Each
gram contains 25 mg prilocaine and 25 mg lignocaine in an emulsifier. When the cream
is applied to the skin of the nose and cocaine is applied to the nasal mucosa, these
fractures can be reduced without additional anesthesia.
Some surgeons prefer to use general anesthesia in the treatment of most patients, but
other authors have observed that nasal fractures can be managed as well with local
anesthesia as they can with general anesthesia, if the injuries are similar. One evaluation
of results 3 months after reduction showed the rates of postreduction nasal obstruction or
external deformity were equivalent whether general or local anesthesia had been used.
Operative Technique
Even simple depressed fractures of the nasal bones are best managed in the operating
room. Preferred instruments for closed reduction are Boies or Ballenger elevators, Asch
or Walsham forceps, or a large Kelly forceps with rubber tubing on each of the blades
Fig. 67.12. The distance from the nostril rim to the nasofrontal angle is measured, and the
instrument is inserted to a point about 1 cm less than the measured distance. The
depressed fragment is elevated by means of force in the direction opposite the fracturing
force, usually anterolaterally. If the opposite nasal bone is displaced laterally, that bone is
moved medially to its normal position. The Asch or Walsham forceps can be inserted one
blade in each nostril or one blade inserted in the nose under the nasal bone and the other
placed on the overlying skin. Pressure must not be exerted too high in the nose (under the
thick nasal bone near the nasofrontal suture), because this area rarely is fractured and
mucosal tears and bleeding can be produced. Reduction usually can be accomplished
with the fragments in position, but digital molding may be necessary for some patients.
Inadequate reduction of the nasal septum prevents satisfactory repositioning of the
external nose in the case of bilateral pyramidal fracture-dislocation. Reducing the
fragments of nasal bone first often reduces the septum simultaneously; if not, the nasal
pyramid usually can be gently elevated with an Asch or a Walsham forceps while
pressure is applied over the displaced septal region.

FIGURE 67.12. Fracture reduction instruments. From
left, Asch septum-straightening forceps, Walsham
septum-straightening forceps, Boies nasal fracture
elevator, Mayo hemostat with rubber tubing, and Killian
nasal septum speculum.



A few difficult cases of septal fracture-dislocation do not respond to closed reduction. In
these instances, elevating the mucoperichondrium on one side often exposes an
overriding or interlocked cartilage fracture that necessitates segmental resection. Open
nasal fractures are managed by means of fracture reduction before repair of the soft-tissue
lacerations.
Any loose or devitalized fragments of bone or cartilage are removed. Although most
nasal and septal fractures can be managed by closed reduction, some remain suboptimally
reduced despite the surgeon's best efforts. It is important to have a plan for progressing to
open reduction in these instances. The first opportunity for reduction provides the best
chance for a good result.
The septum can be stabilized with polymeric silicone splints sutured in place, and gauze
packing is placed in each nasal passage. An external dressing of paper tape, 2-inch-wide
(5 cm) orthopedic plaster, and an external layer of tape is applied. The use of an
intranasal dressing is controversial. Some authors advise routine use of antibiotic-
impregnated gauze for 2 or 3 days, whereas others caution against this practice because
of the danger of toxic shock syndrome. The splints are removed 10 days after the
operation. Decongestants and steroid nasal sprays are useful during the recovery period.
Various nasal splints are available, including several made of heat-sensitive,
thermoplastic materials. After closed reduction and application of paper tape strips, a
thermoplastic splint is placed in hot water and applied over the paper tape. It hardens in a
few seconds and adheres tightly to the underlying tape (6).
One prospective study of patients with nasal fractures showed clearly the correlation
between marked traumatic deformity and poor results after closed reduction. When there
was marked septal deformity, the likelihood of a poor result after closed reduction was
unacceptably high. This emphasized the need for precise diagnosis and frequent use of
open reduction.
Open Reduction
Open reduction usually is mandated when there is concern about the ability to reduce the
nasal pyramid because of an interlocked fracture of the septal cartilage and bones. The
septum is approached through a hemitransfixion incision on the side of dislocation
(complete transfixion incisions predispose to lower tip height and introduce additional
structural instability). Further access to the fracture lines is gained through bilateral
intercartilaginous incisions. The dorsal skin is elevated off the upper lateral cartilages,
and the periosteum is elevated from the nasal bones. Incisions in the piriform aperture
provide access to the lateral fracture lines. Common findings are dislocation of the
quadrangular cartilage off the maxillary crest or C-shaped fracture of septal cartilage and
bone.
The cartilaginous segments are exposed and reduced. Sometimes a segment of cartilage
must be resected adjacent to the fracture. A Cottle elevator or Ballenger swivel knife is
used to excise small strips of cartilage. Radical resection of cartilage or bone is avoided
to preserve support and limit fibrosis and contracture. After septal surgery of this type,
satisfactory reduction almost always can be accomplished. In view of the trend toward
open procedures, a note of caution is added regarding periosteal elevation over nasal bone
fragments, lest they be displaced, devitalized, or lost. Rasping is not attempted near
fracture fragments, and efforts to improve preinjury appearance are minimized. Packing
and splinting are as for closed reduction. Antibiotic coverage is routine. Cold compresses
are recommended for 24 to 48 hours to reduce existing edema and prevent additional
edema. Some authors recommend injecting hyaluronidase to decrease edema Fig. 67.13.

FIGURE 67.13. Algorithm for management of fractures
of the nasal sinuses.



Delayed Management
Delayed management of traumatic nasal deformities is challenging. Bone, cartilage, and
mucosal lining all can be involved. Careful analysis and planning precede the decision to
undertake reconstructive nasal surgery. The more common procedures are variations of
traditional rhinoplasty, septorhinoplasty, or open septorhinoplasty. Surgery usually is
delayed 6 months or more from the initial closed or open fracture reduction to allow
fracture lines to stabilize and fibrosis to mature. Some surgeons recommend a complete
transfixion incision to approach septal deformities. The maxillary crest, anterior spine,
and caudal septum can be visualized through this approach, and appropriate
reconstructive steps (excision, resection, cartilage struts) can be accomplished Fig. 67.14.
A second common problem is the presence of an asymmetric dorsal nasal hump. In these
patients, the nasal bone and the upper lateral and septal cartilages are higher on one side.
The two sides can be evened with removal of this hump Fig. 67.15.

FIGURE 67.14. Open reduction. A: Transfixion incision.
B: Subperichondrial tunnel. C: Subperiosteal tunnel and
vomer osteotomy. D: Removal of deviated or displaced
bone and cartilage. E: Midline repositioning of
quadrangular cartilage and vomer.



FIGURE 67.15. Removal of asymmetric hump.



Deviation of the caudal septum can be managed through a transfixion incision. The
mucoperichondrium is elevated, and limited resection of the caudal septum is performed.
This eliminates some of the deflected cartilage and allows correction of tip depression
along with limited shortening of the nose. Open rhinoplasty is useful in dealing with
severe, complex nasal-septal deformity. Exposure of the critical areas allows direct
visualization and correction of asymmetry of the external nose and septum. A technique
has been described for correcting traumatic nasal asymmetry while leaving the
osteocartilaginous dorsal support intact. The dorsum is resected to a point near the
midline, septoplasty is performed, and augmentation of dorsal, columellar, and tip defects
is accomplished.
Nasal Fractures in Children
A child's nose is more cartilaginous and hence more flexible and resilient than an adult's.
Because of this difference, injury patterns vary from those among adults. There are more
associated injuries, and edema tends to obscure the extent of nasal involvement. Falls are
a more common cause of fractures among children. The possibility of child abuse is
considered if there are unexplained associated injuries or a history of repeated trauma.
Radiographs are less helpful than in the care of adults. Palpation and internal nasal
evaluation are more difficult because children can be apprehensive, uncooperative, and
less able to communicate their responses. The cartilaginous structures are more likely to
be dislocated from adjacent bony structures and to buckle rather than fracture. Greenstick
fractures of nasal and septal bones are more common. Septal hematoma is more common
and more difficult to diagnose and carries more serious implications. In order of
frequency, the signs and symptoms of nasal injury among children are as follows:
1. Epistaxis
2. Nasal dorsum edema
3. Periorbital ecchymosis
4. Tenderness of the dorsum of the nose
5. Abnormal radiographic findings
6. Visible nasal deformity
7. Crepitus of the nasal bones
Other differences are as follows. The fractures begin to heal and become immobile within
2 to 4 days. General anesthesia is nearly always necessary for reduction. Traumatic
damage of growth centers can be caused by injury or surgical management. Conservatism
is the watchword in managing pediatric nasal injuries. Radical procedures are
contraindicated, but septal surgery can be performed safely when it is clearly needed and
when the long-term outcome without surgery is likely to be worse in terms of external
deformity or nasal obstruction. Loss of support, telescoping of fracture fragments, and
nasal deviation are common sequelae of severe nasal injuries among children. Some
surgeons have proposed using an aggressive approach to pediatric injuries in an effort to
deal with the immediate problems (airway and appearance) and to avoid the
consequences of abnormal further growth and development. On the favorable side,
childhood fractures respond more often to closed reduction techniques. If open reduction
is necessary, dissection and excision of tissue are kept to a minimum.
Nasofrontal-Ethmoidal Fractures
When great force is directed from the inferior aspect to the external nose, the nasal bones
can be driven into the frontal and ethmoidal skeleton at the anterior base of the skull. This
type of injury produces comminution and displacement of the nasal, frontal, and ethmoid
bones with telescoping and splaying of these structures. Injury to the nasofrontal duct or
cribriform plate can be associated with these complex fractures. One or both medial
canthal ligaments can attach to fragments that become loosened, causing
pseudohypertelorism. The Horner muscle inserts on the medial ligament and is partially
responsible for this deformity. The medial canthus comprises the medial canthal tendon
and the nasolacrimal sac and canaliculi. The intercanthal distance usually is equivalent to
the interpalpebral distance or half of the interpupillary distance. Associated injuries
include CSF rhinorrhea, anosmia, ocular injury, interruption of the lacrimal system, and
cerebral contusion.
Management consists of open reduction and stabilization of the bone fragments. The
fracture area can be approached with bilateral Lynch incisions connected by a transverse
incision just below the glabella (open sky incision). For some patients this can be
modified to incorporate existing lacerations. The fracture site is disimpacted, and the
bony fragments are reduced and immobilized with wiring. If there is severe comminution,
the fragments must be stabilized with two small lead plates over a soft sponge on each
side of the nasal pyramid. The plates are held in place with a wire suture through both
plates and the interposed nasal pyramid. Better outcomes can be achieved by means of
managing severely comminuted nasoethmoidal orbital fractures with primary structural
reconstruction. Calvarial bone grafts have good resistance to resorption and are well
tolerated in the nasal region. Primary reconstruction can prevent the marked shortening
and deformity often associated with this injury. Split calvarial bone is recommended for
dorsonasal reconstruction because there are fewer long-term complications, excellent
postoperative contour, and a natural feel to the nasal complex (7).
Nasoethmoidal Orbital Fractures
Nasoethmoidal orbital fractures are challenging to diagnose and manage (8). They
usually involve the lateral aspect of the nose, inferior orbital rim, medial orbital ethmoid
wall, nasal maxillary buttress, and frontal process of the maxilla Fig. 67.16.
Nasoethmoidal orbital fractures usually necessitate open reduction with rigid fixation.
Bone grafting sometimes is needed (9).

FIGURE 67.16. The nasoethmoidal orbital region.



Complications
Early
Early, temporary complications include edema, ecchymosis, and hematoma Table 67.3.
They usually resolve spontaneously, but hematoma can be serious enough to necessitate
drainage. The physician searches for septal hematoma in every case of septal injury
because it can become infected and cause loss of septal cartilage and saddle deformity.
Septal hematoma is suspected when any patient has persistent swelling and pain. It is an
especially threatening complication for children. Polymeric silicone splints can be useful
in preventing reaccumulation of blood at the hematoma site.

TABLE 67.3. COMPLICATIONS NASAL
FRACTURES



Epistaxis usually ceases spontaneously, but if recurrent it necessitates control by means
of cauterization, nasal packing, or vessel ligation. Profuse anterior bleeding usually is
caused by laceration of the anterior ethmoidal artery, a branch of the ophthalmic artery
(internal carotid system). Posterior bleeding usually originates from the posterior
ethmoidal artery or the lateral nasal branch of the sphenopalatine artery, and internal
maxillary artery ligation may be needed to achieve hemostasis. If nasal packing is used,
care must be taken not to overpack, because this can impede the vascular supply of a
damaged septum sufficiently to cause necrosis.
Infection is an uncommon complication, but antibiotic prophylaxis is important in the
care of patients who have chronic debilitating diseases, are immunosuppressed, or have
septal or dorsal hematoma.
Cerebrospinal fluid rhinorrhea is rare and is associated with fracture of the cribriform
plate or posterior wall of the frontal sinus. Detection of -transferrin in the nasal
discharge is the most reliable method for diagnosing CSF rhinorrhea. Small leaks often
can be found for 4 to 6 weeks in anticipation of spontaneous closure. Neurosurgical
consultation is standard practice.
Late
Late or delayed complications include airway obstruction, fibrosis or scar contracture,
secondary nasal deformity, synechiae, saddle-nose deformity, and septal perforation
Table 67.4. These complications are best managed with prevention. Following the steps
discussed earlier should help the physician to be aware of the extent of the initial injury.
This awareness is essential in management decision making. There is a long history of
failure to diagnose and adequately manage nasal fractures, but advances in therapy are
reducing these problems.

TABLE 67.4. EMERGENCY CARENASAL
FRACTURES



In one study, nasal fracture was associated with nasofacial disproportion, especially a
long nose, among 21% of patients who were observed long term. Long-nose deformity
developed during puberty, normally a time of rapid growth of the nose. These findings
correlated closely with the observations of other authors, who described three periods of
nasal development: 1 to 6 years of age (rapid growth), 6 to 11 years (slow growth), and
12 to 16 years (rapid growth). The authors recommended that nasal surgery be performed
between the ages of 6 and 11 years when practical.
Emergencies
Emergencies associated with nasal fractures are severe bleeding, nasal airway obstruction
in a neonate, septal hematoma in a child, CSF rhinorrhea, and vision impairment.
Management steps for each emergency are summarized in Table 67.3.
Frontiers of Knowledge
Our ability to evaluate and manage nasal fractures would be improved if clinical trials
were conducted to address several topics. The following are necessary:
1. A prospective, randomized, multicenter clinical trial comparing closed and open
surgical management
2. Clarification of the role of delay in treatment as a factor influencing the outcome
of therapy
3. Clarification of the need for antibiotics (and which specific antibiotic is optimal)
as prophylaxis to prevent infection in certain instances (and which instances)
FRACTURES OF THE FRONTAL SINUS
Fractures of the frontal sinus can be complicated by meningitis and brain abscess. The
management of fractures of the frontal sinus has undergone great change, and several
aspects remain controversial. A variety of surgical procedures exist Fig. 67.17.

FIGURE 67.17. Algorithm for management of fractures
of the frontal sinus.



Epidemiology and Etiology
Twelve percent of facial fractures, excluding mandibular and nasal fractures, are fractures
of the frontal sinus. Frontal and ethmoidal involvement occur among 15% of patients
with head injuries. Men and boys are injured more frequently than women and girls (8:1).
The incidence of fractures of the frontal sinus is greatest in the third decade of life,
although the fractures occur at any age. Motor vehicle accidents are the most common
cause. Other causes include gunshot wounds, physical altercations, sports, industrial
accidents, and falls. The severity of the injury to underlying bone, sinus, dura, and brain
cannot be ascertained from the external appearance of the area. In particular, injuries
penetrating the anterior table are evaluated carefully for possible injuries to the
underlying and surrounding structures.
Anatomy
The two frontal sinuses develop separately and are frequently asymmetric. The sinus has
three sidesanterior, posterior, and floor. The floor of the frontal sinus is the thinnest of
the three and is most convenient for trephination of the sinus. The frontal sinus drains
through the frontonasal opening, usually located in the posterior-medial aspect of the
floor. The course of the frontonasal duct is posterior and caudal. The other relations of
the frontal sinus include the orbit inferolaterally and the cribriform plate, dura, and
frontal lobes posteriorly. The proximity of these vital structures makes them vulnerable to
damage in trauma to the frontal sinus.
Biomechanics of Frontal Sinus Fracture
Of all facial bones, the frontal bone has the highest tolerance of direct trauma. The
anterior wall is thicker than the posterior wall and can withstand 800 to 2,200 (360 to 990
kg) pounds of force. The skulls of women and girls are more fragile and can withstand
less of an impact. High-velocity penetrating injuries to the anterior wall can severely
damage the posterior wall and underlying dura and brain. Damage to the posterior wall
must be suspected in all cases of frontal sinus fracture.
Evaluation
Patients with frontal sinus injuries usually come to medical attention in an emergency and
often have other serious injuries. Initial management is directed at life-threatening
conditions and stabilizing the patient's condition. Patients with severe, compound,
comminuted fractures usually are in a coma. A laceration over the forehead skin can
reveal the interior of the sinus, and foreign material can be found, often a piece of glass.
Cerebrospinal fluid can drain through the wound or nose. Profuse, deep bleeding suggests
a laceration of the superior sagittal sinus or other vessels of the dura and brain. A fracture
of the superior orbital rim can be present, and the globe can be displaced or trapped.
Fracture of the nasoethmoidal complex can manifest as flattening of the pyramid and
telescoping of the nose.
Initial assessment by the trauma team rules out injury to the cervical spine. Radiography
of the cervical spine is the rule if the patient's condition is sufficiently stable. If computed
tomography (CT) is performed, it includes the face and skull. It is optimal that a
neurosurgeon and otolaryngologisthead and neck surgeon work together to manage
severe compound comminuted fractures with intracranial damage. Antibiotics are given
to all patients. The patient is taken to the operating room when his or her condition is
stable enough for general anesthesia. Surgical access is best from a bicoronal flap
approach or an extension of the laceration. The neurosurgeon undertakes dbridement of
the wound, macerated dura, and brain and repairs the damaged dura. The walls and floor
of the frontal sinus and the frontonasal duct are evaluated. Surgical approaches include
obliteration of the frontonasal ductal, obliteration of the frontal sinus, or cranialization.
Closed fractures are not immediately life threatening but can cause intracranial infection.
These patients need head and neck and neurologic examinations, including exclusion of
cervical spinal injury. Palpation can reveal a depressed, mobile anterior table fracture.
Vision status and the possibility of CSF rhinorrhea are assessed. Although the most
common fracture of the frontal sinus is a closed anterior table fracture, the depth of injury
often is difficult to assess. Computed tomography to identify the site of fracture and
surrounding soft-tissue damage is appropriate. Treatment depends on the clinical findings
and radiologic assessment.
Radiologic Evaluation
Before use of CT became widespread, an imaging examination of the skull included plain
radiographs with different views, such as Caldwell, Waters, base, and hyperextended
views. These are useful as initial screening procedures but lack the definition that is
helpful preoperatively. Computed tomography helps identify complex fractures and also
helps to evaluate the soft tissues. Fine axial sections are useful for evaluating anterior and
posterior table fractures of the frontal sinus and intracranial injuries. Coronal scans
provide good definition of the floor of the frontal sinus, frontonasal duct, and cribriform
plate.
Preoperative diagnosis of injury to the frontonasal duct has been difficult even with CT.
In a retrospective review of 19 cases of frontal sinus trauma, the presence of frontonasal
duct injury found at operation was correlated with the findings at preoperative CT. Injury
to the frontonasal duct has occurred among 83% of patients with fractures through the
floor of the frontal sinus and 67% of patients with anterior ethmoidal fractures. Thus the
presence of either of these fractures suggests injury to the frontonasal duct.
Antibiotic Prophylaxis
The aim of antimicrobial prophylaxis is prevention of sinusitis and intracranial sepsis.
Antibiotics with high CSF penetration, such as ceftriaxone or ceftazidine, and
metronidazole for anaerobic cover are good choices when there is risk of intracranial
sepsis. When gram-positive antimicrobial activity is desired, such as skin contamination,
cefazolin can be added. In the management of compound fractures, antibiotic therapy is
maintained for at least 2 weeks. For closed fractures and isolated nondisplaced anterior
table fractures, antimicrobial prophylaxis can be omitted, but some authors recommend
antibiotics in all cases of fractures of the frontal sinus. The foramina of Breschet are a
potential intracranial source of drainage of the frontal sinus mucosa and justify routine
use of antibiotic prophylaxis.
Historical Overview of Frontal Sinus Surgery
Reidel in 1898 performed total ablation of the anterior table of the frontal sinus and
mucosa for a patient with frontal sinus fracture. This allowed the skin to collapse over the
posterior table and obliterate the sinus cavity but also left a cosmetically undesirable
outcome. Lynch (1921) described the external radical frontal sinus operation, which was
successfully used to treat 15 patients with chronic sinusitis; it is now commonly called
external frontoethmoidectomy. In 1951 Bergara and Bergara (10) described an approach
to the frontal sinus whereby the anterior table was hinged on the inferior pedicle of the
pericranium to provide adequate access to the frontal sinus. The bone flap was replaced at
the end of the procedures, and good aesthetic results were obtained. In 1958 Goodale and
Montgomery (11) added total removal of the sinus mucosa and fat obliteration to this
procedure. Other surgeons described a method of reconstituting the anterior table with
free contaminated fragments (after soaking in povidone-iodine) and simultaneous
removal of the posterior table. In cranialization procedures, the anterior sinus wall is in
direct contact with the anterior cranial contents, and the frontal sinus cavity is eliminated.
Either osteoplastic frontal sinus obliteration or cranialization can be used. The condition
of the posterior table is used as a criterion for selection of the approach.
Treatment
The important concepts in the management of fractures of the frontal sinus are (a)
prevention of intracranial sepsis, (b) prevention of frontal sinus disease, such as sinusitis
and mucocele, and (c) a cosmetically acceptable outcome. A management algorithm Fig.
67.16 is a guide to the treatment of patients with fractures of the frontal sinus. Although
most patients fall within this algorithm, it does not replace experienced clinical judgment.
Anterior Table Fracture
Nondisplaced Anterior Table Fractures
Linear nondisplaced or minimally displaced anterior table fractures with no cosmetic
deformity can be managed conservatively. Persistent opacification of the frontal sinus
cavity raises the possibility of injury to the frontonasal duct or even CSF leakage and is
an argument for exploration. Anterior table fractures, however, do not produce injury to
the frontonasal duct unless they are associated with a fracture of the supraorbital rim or
nasoethmoidal complex. Frontal sinus trephination and endoscopic examination may be
worthwhile with a view to possible exploration.
Displaced Anterior Table Fractures
The objective with displaced anterior table fractures is aesthetically acceptable
reconstruction of the anterior table. Surgical access can be gained with a bicoronal or
supraorbital brow incision or extension of an overlying laceration. In nonfragmented or
minimally fragmented cases, reduction of the fractures and stabilization with wires or
microplates is sufficient (Fig. 67.18, Fig. 67.19). In the management of severely
comminuted fractures with bone loss, an effort is made to achieve maximal bone
preservation. The painstaking process of replacing the jigsaw puzzle is used to avoid
cosmetic deformities in the frontal region. Wires or microplates are needed to retain the
fracture fragments in proper position.

FIGURE 67.18. Computed tomographic scan shows
displaced anterior wall fracture of the frontal sinus.



FIGURE 67.19. Frontal sinus anterior wall fracture
reconstruction with miniplate fixation.



Posterior Table Fractures
Nondisplaced Posterior Table Fractures
Asymptomatic linear nondisplaced fractures of the posterior table without CSF leakage
can be observed safely with prophylactic antibiotic treatment. In cases in which persistent
soft-tissue opacification is present at the fracture site, frontal sinus trephination with
endoscopic examination is helpful to prevent cerebral herniation.
Displaced Posterior Table Fractures
Displaced fractures of the posterior table are by definition compound fractures of the
cranial vault Fig. 67.20. In general, all displaced fractures of the posterior wall
necessitate exploration. A large number of these patients have CSF leakage. Which is the
best operation remains to be settled. If there is no posterior wall bone loss, reduction of
the displaced fragment is recommended, and no obliteration is necessary in the absence
of injury to the frontonasal duct. Results of studies conducted with animals indicate that
posterior wall fractures heal if drainage into the nose is maintained. Accurately reduced
fragments heal by means of bony union with mucosal and dural integrity.

FIGURE 67.20. Computed tomographic scan shows
displaced anterior and posterior wall fracture of frontal
sinus with pneumocephalus.



Obliterative procedures on the frontal sinus are recommended to manage posterior wall
fractures without a great deal of bone loss but with injury to the frontonasal duct Fig.
67.21. The operation is designed to prevent retrograde intracranial spread of infection. It
involves obliteration of the frontonasal duct and the frontal sinus cavity. The safety of
obliterative procedures when there is substantial posterior table bone loss has been
questioned, especially when a free fat graft is used in an incomplete cavity. Others have
found obliteration with fat to be a satisfactory procedure.

FIGURE 67.21. Obliteration of frontal sinus with fat
(sagittal view).



Cranialization of the frontal sinus involves excision of the posterior wall. The dura is
allowed to come forward to the anterior table of the frontal sinus Fig. 67.22. The
frontonasal duct orifices are obliterated with bone to prevent retrograde spread of
infection into the cranium and to decrease the risk of formation of encephalocele.
Intracranial complications (CSF leakage, meningitis, and cerebral abscess) have occurred
with both frontal sinus obliteration and cranialization. Unlike cranialization, frontal sinus
obliteration carries the risk of a mucocele. Further studies are needed to determine
optimal surgical management.

FIGURE 67.22. Cranialization of frontal sinus. Anterior
wall reconstructed with fragments from anterior and
posterior walls.



Frontonasal Drainage
The relation between obstruction of the frontonasal duct and formation of frontal
mucoceles has been established. Experiments with animals have shown that mucocele of
the frontal sinus forms if the frontonasal duct is obstructed or when there is inadequate
removal of the mucosa. The frontonasal duct is small and cannot be evaluated confidently
before surgery, even with the help of CT. The best evaluation of frontonasal duct
integrity and patency is made intraoperatively. Frontal sinus exploration is recommended
if injury to the frontonasal duct is suspected.
Patency of the frontonasal duct can be evaluated with fluorescin, benzylpenicillin
solution (white) or methylene blue dye. Intranasal presence of the substance when it is
introduced into the frontonasal duct superiorly indicates the frontonasal duct is patent.
Interpretation of this test result is difficult in the presence of anterior ethmoidal fractures
and swelling of the nasal mucosa.
In the presence of an obstructed frontonasal duct, obliteration of the frontonasal duct
region is recommended. Removal of all mucosa of the frontal sinus is undertaken with a
curet or bur. Obliteration of the frontal sinus cavity is carried out. Free grafts that include
fat, fascia, muscle, pericranium, and cancellous bone have been used. The use of
exogenous materials such as methyl methacrylate and oxidized regenerated cellulose
hemostat has been associated with postoperative abscess formation. A vascularized
transverse glabellar flap for obliteration of the frontonasal duct has been described (12).
This consists of the corrugator supercilii and procerus muscles inserted to the frontal
sinus through a surgically produced window in the superomedial orbital wall (12). The
safety of fat obliteration has been questioned in cases in which a large portion of the
posterior wall is missing. Results of studies with animals have shown high rates of
epithelial regrowth (39%) and infection (44%) with fat obliteration in large posterior
table defects. Fat absorption also can occur. The use of cancellous bone for obliteration
has been advocated, and sinus obliteration by spontaneous osteogenesis from the burred-
down cortex has been recommended.
Complications
Although it is true that more complications are seen with longer follow-up periods,
difficulty often is encountered with sustained follow-up evaluation. The complications
are listed in Table 67.5. Headache and frontal sinus pain are the most common minor
complications after frontal sinus trauma. Meningitis is the most common intracranial
complication. The average time lapse from frontal sinus injury to surgical confirmation of
mucocele is 7.5 years. However, mucoceles have been reported to form after as short a
time as 2 months or as long a time as 42 years, which emphasizes the importance of long-
term follow-up care.

TABLE 67.5. COMPLICATIONS FRONTAL
SINUS FRACTURES




HIGHLIGHTS
The key signs and symptoms of nasal fracture are deformity,
bleeding, swelling, tenderness, false motion, and nasal
obstruction.
A high index of suspicion and early assessment are vital to
detect and manage serious nasal injuries.
Early detection and drainage of septal hematoma are essential
in preventing saddle-nose deformity.
Patients with deviation of the nasal pyramid have serious septal
fractures.
Most nasal fractures can be managed by means of closed
reduction, but complex fractures and those with nasal deviation
greater than one half the width of the bridge necessitate open
reduction.
Open reduction and late nasal reconstruction are difficult
procedures that are performed only by experienced nasal
surgeons.
Motor vehicle accidents are the most common cause of
fractures of the frontal sinus. These fractures commonly occur
among 12% of facial injuries, and the patient usually is a man
or boy in the first three decades of life.
The important concepts in the management of fractures of the
frontal sinus are prevention of intracranial sepsis, prevention of
frontal sinus disease, such as sinusitis and mucocele, and
cosmetically acceptable outcome.
Antibiotic prophylaxis is to be encouraged in all cases of
fractures of the frontal sinus.
Computed tomography is useful for evaluation of fractures of
the frontal sinus both for bony and soft-tissue injury.
Frontonasal duct obstruction can lead to mucocele or
mucopyocele.
Fractures of the frontal sinus involving the supraorbital rim or
nasoethmoidal complex or floor and posterior wall of the
frontal sinus suggest the possibility of injury to the frontonasal
duct.
Frontal sinus trephination with endoscopic examination can be
helpful in ill-defined cases.
Posterior wall fractures usually necessitate exploration; if there
is doubt, exploration is performed.
Frontal sinus obliteration involves removal of all sinus mucosa
and obliteration of the frontonasal duct and frontal sinus.
Frontal sinus obliteration can be complicated by meningitis,
cerebral abscess, and mucocele formation.
Cranialization implies removal of the posterior table and
apposition of the dura to the anterior wall of the frontal sinus. It
can be complicated by meningitis and CSF leakage.
The most common complications of fractures of the frontal
sinus after treatment are headache, sinusitis, and cosmetic
deformity.
CHAPTER REFERENCES
1. Colton JJ, Beekhuis GJ. Management of nasal fractures. Otolaryngol Clin North Am 1986;19:73.
2. Guyuron B, Zarandy S. Does rhinoplasty make the nose more susceptible to fracture? Plast
Reconstr Surg 1994;93:313.
3. Holt GR. Biomechanics of nasal septal trauma. Otolaryngol Clin North Am 1999;32:615619.
4. Sharp JF, Denholm S. Routine x-rays in nasal trauma: the influence of audit on clinical practice. J
R Soc Med 1994;87:153.
5. Newton CR, White PSA. Nasal manipulation with intravenous sedation: is it an acceptable and
effective treatment? Rhinology 1998;38:114116.
6. Drezner DA. Thermoplastic splint for use after nasal fracture. Otolaryngol Head Neck Surg
1994;111:146.
7. Frodel JL Jr. Management of the nasal dorsum in center facial injuries. Arch Otolaryngol Head
Neck Surg 1995;121:307.
8. Hoffman JF. Naso-orbital-ethmoid complex fracture management. Facial Plast Surg 1998;14:67
76.
9. Cheney ML, Gliklich RE. The use of calvarial bone in nasal reconstruction. Arch Otolaryngol
Head Neck Surg 1995;121:643.
10. Bergara AR, Bergara C. Chronic frontoethmoidal sinusitis: osteoplastic method according to
author's technique. Ann Otorhinolaryngol 1955;5:192200.
11. Goodale RL, Montgomery WW. Experiences with osteoplastic anterior wall approach to the
frontal sinus. Arch Otolaryngol 1958;68:271283.
12. Disa JJ, Robertson BC, Metzinger SE, et al. Transverse glabellar flap for obliteration/isolation of
the nasofrontal duct from the anterior cranial base. Ann Plast Surg 1996;36:453457.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

68 PENETRATING FACE AND NECK TRAUMA
Head & Neck SurgeryOtolaryngology
68




PENETRATING FACE AND NECK TRAUMA
MICHAEL G. STEWART

M.G. Stewart: Department of Otolaryngology, Baylor College of Medicine, Houston, Texas.


General Trauma Principles
Penetrating Facial Injuries
Shotgun Injuries
Stab Wounds
Gunshot Wounds
Management of Specific Injuries
Complications
Penetrating Neck Injuries
Zone I Injuries
Zone II Injuries
Zone III Injuries
Management of Specific Injuries
Complications
Chapter References
Head and neck surgeons often manage penetrating trauma to the face and neck.
Knowledge of ballistics, injury patterns, and pertinent anatomy is essential to the
assessment and management of these potentially serious injuries.
The energy imparted into tissue by a penetrating projectile is determined by its kinetic
energy (KE): KE = 1/2MV2, where M is the mass and V the velocity. Because the
velocity term is squared in the equation, high-velocity projectiles impart significantly
larger amounts of energy into the tissue impacted. In other words, a projectile with twice
the velocity will have four times the kinetic energy of a lower velocity projectile.
Typically, firearms are divided into two groups by their muzzle velocity: low velocity
(less than 1,000 feet per second) and high velocity (more than 1,000 feet per second).
Most handguns are low-velocity weapons, with muzzle velocities between 300 and 800
feet per second. A typical shotgun has a muzzle velocity of 1,200 feet per second, and a
30-30 rifle has a muzzle velocity of 2,200 feet per second.
Gunshot wounds cause tissue injury by three mechanisms: direct tissue injury, temporary
cavitation, and transmission of shock waves. Cavitation refers to the creation of a
pulsating temporary cavity surrounding the actual bullet path (Fig. 68.1). This temporary
cavity results in tissue damage and tissue loss adjacent to the missile path. This is an
important concept for the treating physician to understand: Anatomic structures may be
significantly damaged by a gunshot wound without actually being penetrated by the
projectile. In addition to the formation of a temporary cavity, distant shock waves may
also be transmitted from the bullet's path to adjacent tissue and may result in adjacent or
distant tissue damage. Because of their high kinetic energy, high-velocity weapon injuries
tend to have greater cavitation and transmission effects than low-velocity injuries.
Clinically, low-velocity injuries are characterized by tissue damage, whereas high-
velocity injuries are characterized by tissue loss.

FIGURE 68.1. Cavitation effects of a bullet wound to
soft tissue.



In addition, bullets or pellets in flight have several components to their rotation (Fig.
68.2). These rotational characteristics increase the potential that a bullet may take an
erratic course after impact and also may increase the amount of direct tissue injury.
Bullets from high-velocity weapons often have exaggerated amounts of yaw, precession,
and rotation, with the resultant potential for more severe injury. Further, projectiles may
shatter on tissue impact, resulting in secondary projectiles with the potential for
additional injury. Similarly, impacted bone may also shatter, and secondary bone
fragments may cause further tissue damage.

FIGURE 68.2. The rotational ballistics of a missile,
demonstrating yaw, precession, and nutation.



The type of tissue penetrated also influences the effects of a penetrating projectile injury.
Tissues with low elasticity (e.g., bone) tend to shatter or fragment and undergo greater
damage than more elastic tissues (e.g., muscle). Similarly, tissues with high density or
specific gravity (e.g., brain) tend to undergo greater damage than less-dense tissue (e.g.,
lung parenchyma).
GENERAL TRAUMA PRINCIPLES
The basic principles of trauma management apply to all patients with penetrating face
and neck trauma. These trauma principles may be committed to memory using the
mnemonic ABCDE:
A. Assessment of Airway and cervical spine
B. Assessment of Breathing
C. Assessment of Circulation
D. Assessment of Disability and neurologic status
E. Exposure and overall Evaluation of the patient for other injuries.
A useful tool for assessing disability is the AVPU system: A = alert, V = responds to
voice, P = responds to pain, and U = unresponsive (1). The overall prevalence of cervical
spine fracture in patients with facial trauma is 1% to 2%, but all patients should be
considered to have a cervical spine injury until proved otherwise.
In the emergency center, in addition to cervical spine x-ray films, all patients with
penetrating face trauma should have an anteroposterior (AP) and lateral skull and face
roentgenograms, and patients with penetrating neck trauma should have AP and lateral
soft-tissue neck roentgenograms. These films can identify remaining bullets, pellets,
bullet fragments, and bony fragments and may help define the path of the projectile. In
stab wounds where the weapon is still present, the depth of penetration may be identified.
Further, these roentgenograms may reveal the presence of subcutaneous air or tracheal
deviation.
Evaluation of the airway should be the first priority in the emergency center for all
patients with penetrating face or neck trauma. The techniques of airway establishment are
beyond the scope of this chapter, but most patients can be carefully intubated transorally;
if a cervical spine injury is suspected, the patient may be intubated while continuous in-
line neck stabilization is applied. If the airway is unstable and there is significant
bleeding or edema in the oral cavity or pharynx, the patient should undergo
cricothyroidotomy or urgent tracheotomy in the emergency center. Blind nasotracheal
intubation should be avoided, although in the stable patient a fiberoptic-guided transnasal
approach may be appropriate. In penetrating injuries to the neck with obvious tracheal
injury (e.g., sucking wound, significant subcutaneous emphysema), the trachea may be
carefully intubated through the entry wound itself using an armored or reinforced
endotracheal tube.
Once the airway has been stabilized, the remainder of the examination may be completed,
including a careful assessment of entry and exit wounds. When possible, information on
the number of stab or gunshot wounds, the type of weapon, distance from assailant, and
so on may be helpful in wound assessment. The physician should be aware that
projectiles and bones may fragment or shatter, and projectiles may ricochet and change
directions through the tissueboth of which may lead to secondary injuries. Probing
entry and exit wounds or removing blood clots in the emergency center should be
avoided because this may precipitate significant bleeding. In addition, all patients with
penetrating face or neck trauma should be considered for tetanus prophylaxis.
PENETRATING FACIAL INJURIES
Although much attention has been focused on injury patterns and treatment algorithms
for patients with penetrating trauma to the neck, chest, and abdomen, there is a relative
paucity of literature on penetrating injuries to the face. The first attempt to create a
staging system for penetrating facial trauma was created in 1979. The system divided the
face into entry zones I, II, and III, which was confusing, because neck entry zones used
the same nomenclature. Further, zone I was superior to the supraorbital rimswhich
actually could be considered a penetrating intracranial (rather than facial) injury. The
system was modified into entry zones A, B, and C, but the demarcation points between
zones were unclear, and two zones (A and B) actually had similar patterns of injury.
Subsequently, Cole et al. (2) and Chen et al. (3) attempted to simplify facial zoning by
designating two entry zones: midface and mandible (Fig. 68.3). Injury patterns to these
zones are distinct, and the system is easy to remember. An algorithm for the care of
patients with penetrating facial trauma is depicted in Fig. 68.4.

FIGURE 68.3. Midface and mandible zones for
penetrating injuries to the face. (From Chen AY, Stewart
MG, Raup G. Penetrating injuries of the face.
Otolaryngol Head Neck Surg 1996;115:464470, with
permission.)



FIGURE 68.4. Algorithm for the initial management of
patients with penetrating injuries to the face. (From Chen
AY, Stewart MG, Raup G. Penetrating injuries of the
face. Otolaryngol Head Neck Surg 1996;115:464470,
with permission.)



Shotgun Injuries
It is important to remember that shotguns have fairly high muzzle velocity, and close-
range shotgun injuries may impart significant kinetic energy to facial tissue. Recognizing
that the distance from weapon to victim was a key point in shotgun injuries, surgeons
classified shotgun injuries into three groups. Long-range injuries (type 1, more than 7
yards distance between weapon and victim) were characterized by subcutaneous or deep
fascia injuries only, medium-range injuries (type II, 3 to 7 yards distance) were
characterized by injuries to structures deep to the deep fascia, and close-range injuries
(type III, under 3 yards distance) typically created massive tissue destruction. In addition,
in close-range shotgun injuries, the wadding material from the shotgun shell may
become imbedded into the soft tissue and must be thoroughly removed to avoid
subsequent problems with infection.
In one series (3), all patients with shotgun wounds to the face invariably had pellet
penetration of both midface and mandible entry zones, so the zoning system was not
helpful in predicting injury pattern. Therefore, shotgun wounds should be considered as a
separate group. Shotgun wounds to the face have a relatively high prevalence of globe
injury (3), so careful ophthalmologic assessment is important. Although rare, shotgun
wounds to the face may achieve intracranial penetration, so careful evaluation of AP and
lateral skull roentgenograms is mandatory. Similarly, vascular injuries and facial
fractures are rare but potentially possible in shotgun injuries to the face, especially in
close-range injuries.
Stab Wounds
Stab wounds to the face may result in globe injury, vascular injury, and even intracranial
penetration. If the weapon is still in place, AP and lateral skull x-ray films can help
predict the depth of penetration and direct further evaluation. Many authors have noted
that in cases where the knife or weapon is still in place, it is important not to remove or
dislodge it because it may be providing tamponade of injured vascular structures. Rather,
the patient should be taken for angiography with the protruding weapon in place. If major
vascular injury is identified, intravascular balloons may be placed by the interventional
radiologist (or proximal vessels may be isolated by the surgeon), and the weapon may
then be removed under controlled circumstances in the operating room.
Gunshot Wounds
The midface/mandible zoning system is particularly applicable for gunshot injuries to the
face, because the two entry zones have distinct patterns of injury. Gunshot wounds to the
midface have a high prevalence of vascular injury (20%), globe injury (20%), intracranial
penetration (20%), and facial fracture requiring open reduction and internal fixation
(35%) (2,3).
The indications for angiogram in penetrating wounds to the face can be remembered as
the two Ps:
1. Proximity to a major vascular structure, or
2. Penetration posterior to the mandibular angle plane.
If the path of a penetrating projectile traverses near a major vascular structure, angiogram
is indicated. This may be difficult to assess because the path of a projectile after tissue
penetration is not always predictable and secondary (fragmented) projectiles may be
created that take different paths. In addition, because of cavitation and distal shock wave
effects, the bullet may be somewhat distant from the vessel and still cause a significant
injury. A useful anatomic landmark is the mandibular angle plane. The mandibular angle
plane is an imaginary vertical coronal plane at the level of the angle of the mandible (Fig.
68.5), and penetration of a projectile or weapon posterior to this plane is an indication for
angiography.

FIGURE 68.5. Lateral view of the face demonstrating
the mandibular angle plane (MAP).



Gunshot injuries to the mandible entry zone often require emergency establishment of an
airway because of bleeding, edema, or hematoma formation in the oral cavity or pharynx
(3). These patients may appear initially to have a stable airway and then quickly
decompensate and require an emergency airway. Although more common with mandible
entry (about 50% of patients), 25% to 35% of patients with midface gunshot wounds may
require an emergency airway (3). Therefore, a high index of suspicion and early elective
airway establishment, when indicated, are important for airway management of patients
with gunshot wounds to the face. The relatively thick bone of the mandible may also
deflect the path of bullets into the neck, into major vascular structures, or into the
intracranial cavity.
Computed tomography, with its multiplanar images, has significantly changed the
management of penetrating facial injuries. Although airway establishment, hemodynamic
stabilization, treatment of other serious injuries, and angiography should take precedence,
axial and coronal computed tomography of the face often significantly aids the head and
neck surgeon in the assessment of damage and improves treatment planning. Figure 68.6
shows an example of the type of injury for which computed tomography is a valuable
diagnostic tool for identifying the extent of injuries and the location of bullet fragments
and secondary projectiles.

FIGURE 68.6. Computed tomography of the face in a
patient with a gunshot wound to the maxilla,
demonstrating fragmentation of both bone and the bullet,
with secondary fragments distributed over a large area.



Management of Specific Injuries
Facial Nerve Injury
Patients with penetrating facial trauma and immediate paralysis of one or more branches
of the facial nerve are likely to have transection of the nerve. If their medical condition
permits, these patients should undergo local exploration with primary nerve repair or
nerve grafting if the wound is lateral to the lateral canthus. Nerve injuries medial to the
lateral canthus are typically not explored because nerve regeneration is usually adequate.
Branches to the forehead and ramus mandibulae should be repaired because cross-
innervation to these areas is poor; branches to the midface may recover function through
cross-innervation even if completely transected (4). Severed distal branches retain
electrical excitability for about 48 hours, and a nerve stimulator may be used
intraoperatively. The preferred neurorrhaphy technique is to trim back the perineurium
away from the anastomosis and perform epineurial repair with 9-0 or 10-0 monofilament
suture (4). Facial nerve injuries that progress from partial to total paralysis after injury or
injuries that only present several hours after injury are usually secondary to edema and
may be treated expectantly.
Parotid Duct Injury
Wounds to the cheek below the zygomatic arch that injure the buccal branch of the facial
nerve are also likely to injure the parotid duct. If parotid duct injury is suspected (e.g.,
clear saliva draining from a penetrating cheek wound or sialocele formation), the wound
should be explored and the duct primarily repaired over a stent.
Complications
Even without intracranial penetration or major vascular injury, penetrating wounds to the
face have the potential for early and late complications in 15% to 35% of patients (2,3).
Potential complications are listed in Table 68.1. Although some are directly attributable
to the injurysuch as blindness or facial nerve injurysome complications are
potentially preventable with early recognition and aggressive management. In particular,
nasal obstruction and stenosis, sinusitis, and choanal stenosis may be prevented with
intranasal dbridement, placement of nasal stents, and the techniques of functional
endoscopic sinus surgery to restore adequate sinus drainage. In addition, diplopia and
orbital or periorbital infections may be prevented with careful reconstruction of the
orbital floor to restore orbital anatomy and isolate the maxillary sinus from the orbital
contents. Further, trismus and malocclusion may be prevented with adequate
maxillomandibular fixation and early mobilization and stretching of the
temporomandibular joint.

TABLE 68.1. COMPLICATIONS
PENETRATING FACE AND NECK INJURIES



PENETRATING NECK INJURIES
The complex anatomy of the neck requires careful assessment of missile trajectory and
site of entry. The neck can be divided into two triangles using the sternocleidomastoid
muscle (Fig. 68.7). The anterior triangle contains most of the major anatomic structures
of the neck: the larynx, trachea, pharynx, esophagus, and major vascular structures. The
major structures of the posterior triangle are muscles, the spinal accessory nerve, and the
spinal column. The platysma muscle lies just deep to the skin of the neck only in the
anterior triangle. Wounds that penetrate the platysma have the potential for serious
injury; wounds that do not penetrate the platysma are superficial by definition and do not
require further evaluation.

FIGURE 68.7. Anatomic triangles of the neck. The neck
is divided into anterior and posterior triangles by the
sternocleidomastoid muscle.



The neck has been divided into three horizontal entry zones to help predict injury patterns
and guide diagnostic evaluation and treatment (Fig. 68.8). Zone I comprises the root of
the neck inferior to the inferior border of the cricoid cartilages, zone II consists of the
neck between the angle of the mandible and the inferior border of the cricoid cartilage,
and zone III comprises the neck superior to the angle of the mandible up to the skull base.
Zone II is the largest zone and the most common site of entry in penetrating neck trauma
(1). McConnell and Trunkey (1) combined the results of 16 large series and found that
the most commonly injured structures in the neck were the larynx and trachea
(considered as a group, 10% of patients) and the pharynx and esophagus (considered as a
group, 10% of patients). The most common vascular structures injured were the internal
jugular vein (9%), the internal and common carotid arteries (7%), the subclavian artery
(2%), and the external carotid artery (2%). The vertebral artery was injured in only 1% of
patients in the combined review.

FIGURE 68.8. Horizontal entry zones of the neck for
penetrating injuries to the neck. (Modified from
Jurkovich GJ. The neck. In: Moore EE, ed. Early care of
the injured patient. Toronto: B.C. Becker, 1990:126, with
permission.)



The overall mortality rate for penetrating neck trauma at most major centers is 3% to 6%
(1). The major cause of death in patients with penetrating neck trauma is exsanguinating
hemorrhage from a vascular injury. Other causes include spinal cord injury, cerebral
ischemia, airway obstruction, air embolism, and pulmonary embolism. Most series report
at least some mortality from missed esophageal injuries, which usually manifest as sepsis.
A careful clinical examination with knowledge of the pertinent anatomy is an accurate
predictor of the extent of injury in penetrating neck trauma. The clinical signs and
symptoms of significant neck injury are listed in Table 68.2. Of course, patients with
refractory shock, uncontrollable hemorrhage, or evolving neurologic deficit should
undergo immediate neck exploration. The surgeon should be prepared to control and
repair major injuries to the carotid artery or jugular vein. Patients who are clinically
stable but have signs or symptoms of injury to a major neck structure should undergo
directed evaluation with subsequent repair of injured structures. The management of the
asymptomatic patient with penetrating neck trauma is controversial, however.

TABLE 68.2. DIAGNOSIS PENETRATING
NECK TRAUMA



Traditionally, all patients with penetrating neck wounds that penetrated the platysma
whether symptomatic or notunderwent neck exploration. The rationale was that the
sensitivity of neck exploration was high and the morbidity of the surgery itself was low,
whereas the morbidity of a missed injury was potentially fairly high. If mandatory neck
exploration was used, negative exploration rates of 30% to 50% could be expected. Over
time, however, trauma surgeons have begun using the angiogram as a diagnostic tool in
selected neck injuries. Further, as the techniques and skills of interventional radiology
have developed, some vascular injuries are now amenable to embolization and definitive
treatment by the interventional radiologist. In addition, there is evidence that directed
examination with observation and serial examinations may be as effective as mandatory
exploration in selected patients (5). These issues are discussed further subsequently. A
simplified protocol for penetrating neck trauma is depicted in Fig. 68.9.

FIGURE 68.9. Algorithm for the initial management of
patients with penetrating injuries to the neck. (Modified
from Mansour MA, Moore EE, Moore FA, et al.
Validating the selective management of penetrating neck
wounds. Am J Surg 1991;162:517521, with permission.)



As in penetrating injuries to the face, the mechanism of injury is important for the
treating physician to consider. Although the depth of penetration of stab wounds may be
difficult to assess, stab wounds tend to injure only the tissue directly penetrated. Gunshot
wounds, however, may cause significant tissue loss and damage to adjacent structures
because of cavitation and shock wave effects.
Zone I Injuries
Penetrating injuries that enter zone I of the neck are potentially lethal because of the
potential for injury to the great vessels of the neck and mediastinum and to the cervical
and thoracic esophagus. Most trauma centers advocate routine angiography of the aortic
arch and great vessels, along with an esophageal evaluationwhether or not the patient is
symptomatic (1). Up to one third of patients with a clinically significant zone I injury
may be asymptomatic at presentation (5). Angiography of the great vessels can identify
those patients who need a midline sternotomy or thoracotomy for vascular control.
Further, mandatory esophageal evaluation is recommended because a missed zone I
esophageal injury is potentially different from a missed zone II injury. An esophageal or
pharyngeal injury in zone II will usually develop clinical signs or symptoms (such as
subcutaneous emphysema) within a few hours, and overall morbidity and mortality may
not be affected. A missed esophageal injury in zone I, however, may be clinically silent
until sepsis and mediastinitis develop. Opinions on the best diagnostic test for esophageal
injury differ, but the sensitivity of both esophagoscopy and contrast esophagography are
about 80% to 90%. Using both esophagoscopy and esophagography together probably
increases sensitivity and specificity to near 100%.
In a recent study of 138 patients with penetrating zone I injuries, 36 patients had normal
findings on physical examination and chest radiographs. The authors concluded that in
view of this negative predictive value of 100%, arteriography is not necessary in this
situation (6). Similarly, analysis of another recent large series of patients with penetrating
neck injuries of zones II and III supports the concept that thorough physical examination
and observation of these patients is appropriate in asymptomatic patients and that neither
routine arteriography nor surgical exploration is mandated (7).
Zone II Injuries
Patients with penetrating zone II injuries who are symptomatic should undergo neck
exploration. Asymptomatic patients with penetrating zone II injuries may be treated with
either mandatory exploration or directed evaluation and serial examinations. Mansour et
al. (5) treated 188 patients with neck injuries to the anterior triangle that penetrated the
platysma using the following protocol. All symptomatic patients were explored, although
those with zone I and zone III injuries first underwent angiography. Asymptomatic zone I
patients also underwent angiography and esophageal evaluation, but asymptomatic zone
II and III patients were admitted and underwent ancillary testing (such as angiography)
based on missile trajectory, followed by serial examinations by a physician every 6 hours.
The authors noted that the observed patients did very well as a group, with virtually no
missed injuries, morbidity, or mortality and a shorter average length of stay than the
patients who underwent exploration.
In another study, surgeons treated 120 consecutive patients with penetrating zone II
injuries using the following protocol. All unstable patients underwent immediate neck
exploration. All other patients (whether symptomatic or not) underwent clinical
assessment, arteriography, laryngotracheoscopy, flexible esophagoscopy, and barium
swallow, and then all patients underwent neck exploration. The authors reported that five
patients had six injuries that had been missed by the diagnostic evaluation. They
concluded that even a thorough clinical assessment was inadequate for detecting injuries
to vital structures and recommended mandatory neck exploration for all zone II injuries.
Others, however, noted that some of the missed injuries (two internal jugular vein
injuries, two carotid artery injuries) may have been clinically insignificant and that others
(two esophagus injuries) would have been detected within hours using serial
examinations. Therefore, some trauma surgeons have used these data to support directed
evaluation with serial examinations for asymptomatic patients with zone II injuries,
which is the opposite conclusion of the authors of the paper. The data from this series
also allow the calculation of positive and negative predictive values of the diagnostic
tests used. Using neck exploration as the gold standard for identifying injuries, clinical
assessment alone had a positive predictive value of only 47% and a negative predictive
value of 86%. Flexible esophagoscopy had a positive predictive value of 88% and a
negative predictive value of 94%; barium swallow had similar values, with a positive
predictive value of 83% and a negative predictive value of 95%.
In summary, asymptomatic patients with penetrating zone II injuries may be treated with
either mandatory neck exploration or directed evaluation and serial examinations.
However, a treatment protocol using observation with serial examinations requires
adequate physician staff and a 24-hour facility prepared for emergency testing and
surgery at any time. Early neck exploration with prompt discharge home for negative
explorations is an efficient and time-tested method of managing penetrating zone II
injuries and, in some settings, may be more cost-effective than multiple tests and
observation.
Zone III Injuries
Penetrating injuries to zone III have the potential for injury to major blood vessels and
the cranial nerves at or near the skull base. Up to one fourth of patients with arterial
injuries may be asymptomatic at presentation (8). In addition, surgical exposure and
control of bleeding in this location may be quite difficult. Further, some of these injuries
are amenable to definitive treatment by an interventional radiologist, particularly injuries
to the internal carotid artery at the skull base, branches of the external carotid artery, and
the vertebral artery (1). Therefore, the injury may be treated under local anesthesia in the
same setting as the diagnostic angiogram. Although vertebral artery injury appears to be
relatively rare, this may be the result of infrequent use of four-vessel angiography in
many series. Therefore, the benefit of routine four-vessel angiography is not clear.
Certainly, however, if the bullet path is near the vertebral column, the vertebral arteries
should be imaged.
Management of Specific Injuries
Vascular Injuries
As noted earlier, blood vessels are commonly injured in penetrating neck trauma.
Whenever possible, primary repair of the injured vessel is ideal. The value of arterial
repair in the face of focal neurologic deficit or coma is controversial, but most vascular
surgeons tend to favor revascularization in cases of traumatic vascular injury (1). In some
cases of carotid artery injury, use of a shunt may improve outcome. In any event, the
assistance of an experienced vascular surgeon is strongly recommended in these cases.
Laryngotracheal Injuries
The management of penetrating injuries to the larynx has been well described and is
described in detail in Chapter 63. If the thyroid or cricoid cartilage has been damaged,
open repair with internal fixation is recommended. If the cartilage is calcified, 1.0- or 1.3-
mm bone plates and screws may be used; if the cartilage is not fully calcified, the
technique of Austin et al. (9) for open reduction and internal fixation is recommended. If
the endolaryngeal mucosa has been disrupted, tracheotomy with midline thyrotomy and
direct repair of mucosal injuries with small absorbable sutures is used. Endolaryngeal
stents are seldom used in penetrating trauma because the structural framework of the
larynx is usually intact (unlike in blunt trauma), although stents may be used if the
anterior commissure has been injured.
Tracheal injuries usually can be closed primarily in two layers: an inner layer of
absorbable suture incorporating the mucosa (with the knots on the outside of the lumen)
and an outer layer of permanent suture securing cartilage ring to cartilage ring in a
submucosal plane. Patients are usually kept intubated for 2 to 3 days and then extubated
under controlled circumstances. Gunshot wounds to the trachea may result in tissue loss,
which may compromise the safety of primary closure, because minimal tension at the
suture line is a key component of successful tracheal repair. Once the wound edges have
been dbrided, superior or inferior tracheal release techniques may be necessary to
achieve a tension-free closure (Table 68.3).

TABLE 68.3. EMERGENCIES PENETRATING
FACE AND NECK INJURIES



Pharyngeal and Esophageal Injuries
Missed injuries to the pharynx and esophagus are a significant source of morbidity and
mortality in penetrating neck trauma. All patients with clinical signs or symptoms of
pharyngeal or esophageal injury (e.g., subcutaneous emphysema, hematemesis,
hypopharyngeal blood) should undergo neck exploration. Intraoperative esophagoscopy
with methylene blue or air insufflation may be helpful in identifying the location of
pharyngeal or esophageal penetration, especially in stab injuries. Up to 50% of patients
with pharyngeal and esophageal injury, however, may be asymptomatic at presentation.
In an asymptomatic patient, if injury is suspected based on missile trajectory, the
combination of esophagoscopy and contrast esophagography is probably most sensitive at
detecting injury.
Penetrating injuries to the hypopharynx that are superior to the level of the arytenoid
cartilage may be treated somewhat differently from hypopharyngeal injuries inferior to
the level of the arytenoid (10). Primary closure is not always necessary in penetrating
injuries to the upper hypopharynx (10); in other words, patients may be treated with
parenteral antibiotics and kept without oral intake for 5 to 7 days. Injuries to the
hypopharynx inferior to the level of the arytenoid cartilage (e.g., in the dependent portion
of the hypopharynx, where saliva and secretions tend to pool) should be treated with
primary watertight closure using absorbable suture with drainage of the adjacent neck
space (10). The patient should be kept without oral intake while the repair heals
typically 5 to 7 days. Injuries to the cervical esophagus may be treated similarly to those
of the inferior hypopharynx, with watertight closure and drainage (11). External drainage
and bypass procedures (e.g., cervical pharyngostomy) should be avoided whenever
possible.
If the cervical spine has been violated by a transpharyngeal bullet, the patient is at risk for
cervical osteomyelitis. Careful wound debridement with removal of all bullet fragments
and devitalized tissue along with parenteral antibiotics should be considered, along with
consultation from neurosurgical or orthopedic colleagues.
Complications
The complications of penetrating neck injuries are listed in Table 68.1. Most
complications are directly attributable to the injury itself, but some are potentially
preventable. The potentially preventable injuries (e.g., neck abscess, pharyngocutaneous
fistula) are usually due to missed or delayed diagnoses, so the best way to avoid these
complications is to be thorough and vigilant in the initial evaluation for injuries and the
immediate follow-up period after treatment. Although less common than 50 years ago,
the mortality of penetrating neck trauma remains 3% to 6%.
In some hospitals, percutaneous dilational tracheotomy has been introduced for the
management of airway problems in the emergency room and the intensive care unit. A
recent review of the experience at one major center reported a high complication rate and
emphasized the risk of posterior tracheal wall perforation and pneumothorax in 29% of
the patients (12).

HIGHLIGHTS
Patients with penetrating trauma to the face and neck should
undergo systematic evaluation using the advanced trauma life
support protocol (ABCDE). Airway establishment is the first
priority, particularly in gunshot wounds to the mandible and
midface zones.
High-velocity gunshot wounds have high kinetic energy and
tend to cause tissue loss and secondary injuries.
Close-range shotgun wounds have high kinetic energy and may
cause massive tissue destruction. Always remove the
wadding material from soft tissues in close-range shotgun
wounds.
Shotgun wounds to the face have a high prevalence of globe
injury. Gunshot wounds to the midface may cause injury to the
globe, may injure major vascular structures, or may achieve
intracranial penetration.
The indications for arteriogram in penetrating facial wounds are
proximity to a major vascular structure or penetration posterior
to the mandibular angle plane.
Classification of penetrating neck wounds into entry zones I, II,
and III helps to direct management. Injuries that penetrate the
platysma have the potential to damage important neck
structures. Most of the vital structures of the neck are in the
anterior neck.
Bleeding, expanding hematoma, shock, and evolving
neurologic deficit suggest vascular injury.
Subcutaneous emphysema, dyspnea, airway obstruction,
hoarseness, or stridor suggest laryngotracheal injury.
Subcutaneous emphysema and dysphagia suggest
pharyngoesophageal injury, but up to 50% of patients will have
no clinical signs of injury.
Patients with symptoms of injury to important neck structures
should undergo neck exploration, except stable patients with
zone I or zone III injuries; preoperative angiography and
esophageal evaluation may help direct the surgical approach or
may identify vascular lesions amenable to treatment by the
interventional radiologist.
CHAPTER REFERENCES
1. McConnell DB, Trunkey DD. Management of penetrating trauma to the neck. Adv Surg
1994;27:99119.
2. Cole RD, Browne JD, Phipps CD. Gunshot wounds to the mandible and midface: evaluation,
treatment and avoidance of complications. Otolaryngol Head Neck Surg 1994;111:739745.
3. Chen AY, Stewart MG, Raup G. Penetrating injures of the face. Otolaryngol Head Neck Surg
1996;115:464470.
4. Coker NJ. Management of traumatic injuries to the facial nerve. Otolaryngol Clin North Am
1991;24:215227.
5. Mansour MA, Moore EE, Moore FA, et al. Validating the selective management of penetrating
neck wounds. Am J Surg 1991;162:517521.
6. Eddy VA. Is routine arteriography mandatory for penetrating injury to zone 1 of the neck? Zone 1
penetrating neck injury study group. J Trauma Injury Infect Crit Care 2000;48:208213,
discussion 213214.
7. Biffl WL, Moore EE, Rehse DH, et al. Selective management of penetrating neck trauma based on
cervical level of injury. Am J Surg 1997;174:678682.
8. Sclafani SJA, Cavaliere G, Atweh N, et al. The role of angiography in penetrating neck trauma. J
Trauma 1991;31:557563.
9. Austin JR, Stanley RB, Cooper DS. Stable internal fixation of fractures of the partially
mineralized thyroid cartilage. Ann Otol Rhinol Laryngol 1992;101:7680.
10. Fetterman BL, Shindo ML, Stanley RB, et al. Management of traumatic hypopharyngeal injuries.
Laryngoscope 1995;105:813.
11. Armstrong WB, Detar TR, Stanley RB. Diagnosis and management of external penetrating
cervical esophageal injuries. Ann Otol Rhinol Laryngol 1994;103:863871.
12. Trottier SJ, Hazard PB, Sakabu SA, et al. Posterior tracheal wall perforation during percutaneous
dilational tracheostomy: an investigation into its mechanism and prevention. Chest
1999;115:13831389.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

69 COMPLEX FACIAL TRAUMA WITH PLATING
Head & Neck SurgeryOtolaryngology
69




COMPLEX FACIAL TRAUMA WITH PLATING
ROBERT M. KELLMAN
SHERARD A. TATUM

R.M. Kellman and S.A. Tatum: Department of Otolaryngology, State University of New York Upstate
Medical University, Syracuse, New York.

Bone Healing
Fracture Pathophysiology and Classification
Rationale for Rigid Fixation
Basic Principles of Rigid Fixation
Fixation Device Classification and Terminology
Principles of Screw Application
Lag Screw Application
Plate Application
Instrumentation
Fracture Reduction
Occlusion
Incisions and Exposure
Approach to Panfacial Fractures
Soft-Tissue Loss
Complications and Revisions
Chapter References
In this age of rapid transportation and increasing urban violence, massive facial trauma is
an entity that the otolaryngologisthead and neck surgeon is likely to encounter. Complex
facial trauma may refer to blunt and/or penetrating trauma resulting in multiple facial
fractures and varying degrees of soft-tissue injury or loss.
Skeletal facial trauma is frequently subdivided into fractures of the frontal sinus,
nasoethmoid complex, zygomaticomaxillary complex, midface, dentoalveolar structures,
mandible, and other unusual fracture patterns. Complex facial trauma can then refer to
either the multiplicity of areas involved (i.e., panfacial fractures) or the degree of severity
of involvement of a given area. For purposes of this chapter, massive facial trauma refers
to high-energy blunt or penetrating trauma leading to severe bony displacement,
comminution or frank bone loss, and/or involvement of multiple anatomic areas and
reducing the availability of anatomic reference points for fracture reduction. The
aforementioned may or may not be additionally associated with severe soft-tissue
lacerations, avulsions, or globe or central nervous system injuries. Regardless of the
precise definition of massive facial trauma, it is our contention that these injuries can be
successfully managed by adherence to the same basic principles that lead to successful
outcomes from less complex trauma.
BONE HEALING
Bone is a complex tissue made up of a collagen matrix mineralized with calcium
phosphate (hydroxyapatite) crystals. Interspersed within bone are cellular components
that mediate bone resorption, deposition, and metabolism. Thicker areas of bone typically
involve two structural components: an outer cortical or dense bone layer and an inner
cancellous or spongy bone layer. Thinner sections of bone are lamellar and lack
significant cancellous bone or marrow space. Nutrition is supplied to bone through the
outer layer of periosteum and inner open circulation of the marrow space (1).
Fracture results in disruption of the bone matrix, surrounding soft tissue, and, if
applicable, marrow space. This disruption allows blood and inflammatory cells to flood
the area. A hematoma forms, which matures through granulation tissue, fibrous tissue,
cartilage, and then bone or directly from fibrous tissue to bone depending on the
embryologic origin. This callous formation allows indirect healing to occur when the
edges of the bone are not approximated. Mineralization eventually occurs if motion is not
excessive. If not anatomically reduced, segments heal in a new position, which may lead
to deformity and dysfunction (2).
If the distance between bone fragments is reduced by anatomic reduction of the fracture,
then healing will occur with reduced callous formation and diminished alteration of
anatomy. Areas of the fracture that are abutted and compressed will heal by contact
healing or direct osseous formation without callous formation. Direct osseous healing is
not likely to occur along the full length of a fracture even if it is well reduced. Microgaps
heal by callous formation or gap healing in which bone is laid down directly
perpendicular to its normal orientation followed by remodeling to change this orientation.
Regardless, the fragments heal in anatomic position (3).
Problems with the bone-healing mechanism can lead to clinical complications of
fractures. Delayed union refers to reduced or absent mineralization of a fracture line 8 to
12 weeks after immobilization. Malunion occurs when a fracture heals by osseous union
with segments in nonanatomic position. Fibrous union occurs when progression of
indirect healing to ossification does not occur. A nonunion can refer to fibrous union,
although it typically connotes a wider gap with very poor function, whereas fibrous
unions may not result in a functional deficit. Pseudoarthrosis refers to a fibrous union that
is mobile enough to function like a joint. This phenomenon might be a desirable result for
a subcondylar fracture that has resulted in temporomandibular joint ankylosis. Otherwise
the mobility leads to dysfunction and pain. Inadequate stabilization and infection are
major causes of these healing problems (4).
FRACTURE PATHOPHYSIOLOGY AND CLASSIFICATION
Fractures occur when forces are applied that exceed the stress capabilities of bone,
leading to a disruption of the mineralized matrix with additional disruption of the
associated soft tissue. Fractures may be simple, involving a single disruption between two
bone segments, or comminuted, meaning multiple bony fragments exist in the separation
between bone segments. Displacement refers to the alteration in anatomic relationships of
bony segments. This alteration can occur as a result of the energy of the blow itself or
because of unopposed muscle pull. Angulation is the change in angle of the long axis of
the bone across the fracture. Distraction refers to the distance between bone segments
across a fracture, and rotation is the orientation alteration of bone segments along their
long axis. A fracture is considered favorable if it is oriented such that muscle pull vectors
act to compress the fracture. An unfavorable fracture is one oriented such that muscle
pull vectors act to displace the fragments (Fig. 69.1).

FIGURE 69.1. A: Posterior body fracture with
unfavorable angulation. Pull of masseter muscle distracts
fracture. B: Favorable posterior body fracture. Pull of
temporalis muscle compresses fracture. C: Unfavorable
fracture. Pull of hyomandibular musculature distracts
fracture. D: Favorable fracture orientation. Pterygoid
musculature compresses fracture. E: Unfavorable fracture
orientation. Pterygoid musculature distracts fracture.



The concept of open or compound fractures relates to the exposure of fractured bone
outside the soft tissue, leading to bacterial contamination. This idea is a little confusing in
the face because of the oral, nasal, and sinus cavities. Certainly, fractures involving gross
lacerations of facial skin or oral mucosa exposing bone are open fractures. Typically,
fractures involving tooth-bearing bone even without mucosal laceration are considered
open because of exposure to the oral flora through the periodontal tissue. Fractures
through the nasal cavity involving mucosal lacerations are likewise exposed to nasal
flora. Fractures through an uninfected sinus cavity may not initially involve bacterial
contamination; however, a blood-filled sinus is likely to become colonized fairly quickly.
Therefore, few facial fractures would not be considered open. Isolated mandibular ramus
or subcondylar fractures and zygomatic arch fractures are among these.
The amount of energy associated with the injury tends to affect the characteristics of the
injury. Low-energy impacts such as fist blows tend to lead to less comminuted and less
displaced fractures. High-energy impacts are more typically associated with
comminution, greater displacement, and a greater degree of soft-tissue injury. The rate of
energy dissipation into the tissue is the true determinant. A hard object striking the face is
more likely to lead to comminution than a fist striking with the same energy because the
energy of the blow is transferred to the tissue more quickly. The kinetic energy of the
object may be greater as well. Penetrating trauma is similar, with low-energy missiles
creating less injury than high-energy missiles. However, missile design comes into
consideration. A high-energy missile with a hard surface may exit the body fairly
quickly, not dissipating all its energy into the body. A lower energy missile designed to
expand, spiral, or tumble and dissipate most of its energy before exit can be more
damaging. But the amount of shock wave energy from the missile impact determines the
degree of collateral tissue damage. Point-blank gunshot wounds have the added soft-
tissue injury of the expanding propellant gases. This blast injury can lead to poor healing,
infection, and fibrosis. Ballistics information is helpful, but wound evaluation is still the
best guide (5).
RATIONALE FOR RIGID FIXATION
Regardless of the etiology or classification of the fracture, the healing mechanism can be
assisted with reapproximation of the fragments followed by fixation to create stability
and reduce movement of the bone fragments. Decreasing movement of the bone
fragments enhances ossification and the progression to a bony union. Reestablishment of
blood supply to devascularized bone fragments or bone grafts is also enhanced by
immobility. This lack of movement or stability requires overcoming the biomechanical
forces acting on the bone fragments. Varying degrees of stability are imparted by
different fixation techniques. Rigid fixation of fractures with plates and screws is thought
to provide superior stability by overcoming functional forces applied by the
musculoskeletal system across a fracture (6). This concept is not universally accepted,
however. Enhancements in imaging capabilities and surgical exposure techniques and a
greater interest in maxillofacial trauma have paralleled the development of plating
technology. These developments may account for improved trauma outcomes.
Additionally, plates have been criticized for palpability, occasional visibility, causing
temperature sensitivity, inhibiting growth, and weakening bone by stress shielding. Some
of these criticisms are more theoretic than others, but absorbable plating systems promise
to alleviate most of these problems.
BASIC PRINCIPLES OF RIGID FIXATION
The central concept of rigid fixation is to return skeletal fragments to their anatomic
position and rigidly fixate them in that position with an implantable device that provides
sufficient strength across the fracture to maintain the reduction against musculoskeletal
forces. Metallic plates are designed to span a fracture and provide stress shielding and
fracture stability. The plates are fixed to the bone with screws. Each screw placed in the
bone is a fixation point. Larger plates made of stiffer material provide greater stress
shielding and stability. Large screws provide stronger fixation than small screws.
Bicortical screws provide greater stability than monocortical screws, and increasing the
number of screws or fixation points anchoring a plate to a bone segment increases
stability. Compression or loading of the bone across the fracture enhances stability by
increasing the friction between the fracture edges (7). Additionally, plate location relative
to bone thickness and the many complex forces acting on the bone are important. Greater
bone thickness allows for longer screws, providing greater stability. Forces acting to
angulate a fracture distract one end of a fracture and compress the other. A plate placed
closer to the end being distracted is more likely to overcome those forces than a plate
located at the end being compressed because of mechanical advantage related to the lever
principle (Fig. 69.2).

FIGURE 69.2. Muscle pull distracts superior border of
fracture and compresses inferior border of fracture. Plate
placement in A prevents superior distraction. Plate
placement in B does not.



The above statements are true within certain limitations. The more rigid a plate is, the
more precise the bending of the plate has to be to conform to the surface contours of the
bone where it is to be applied. Otherwise, as the screws are tightened, the bone may be
pulled toward the plate, creating distraction (Fig. 69.3). Frequently, monocortical
miniplates are adequate to replace a heavy bicortical plate (8). Additional fixation points
(i.e., screws) provide additional stability; however, the incremental increase in stability
decreases as the number of fixation points increases. The increase in stability must be
weighed against the additional exposure required and higher bulk of the larger implant.
Increasing screw diameter must be weighed against the weakening of the residual bony
buttress created by increasing the screw hole size. Increasing screw length into cancellous
bone adds little additional strength unless a second cortex is engaged. Screw length
beyond the applicable bone thickness certainly adds no strength, and damage to
underlying structures such as tooth roots could occur.

FIGURE 69.3. A: Plate is bent to appropriate contour
with bony cortex so that when screws are tightened,
lingual and buccal cortices are approximated. B: Plate is
underbent, approximating buccal cortex but distracting
lingual cortex. C: Plate is overbent, approximating
lingual cortex but distracting buccal cortex.



FIXATION DEVICE CLASSIFICATION AND TERMINOLOGY
The terminology applied to plating systems is confusing and nonuniform, because it is
applied differently by different manufacturers. Plating systems are usually identified
either by their dimensions or by their application. The term miniplate typically refers to
plates designed for screws in the 1.2- to 2.5-mm range. The term microplate refers to
plates designed for screw diameters around 1 mm. There are several intermediate sizes
and now modular systems with multiple plate and screw dimensions. Larger systems are
designed specifically for the mandible with screw diameters up to 3 mm or more and
greater lengths for bicortical applications, including lengths up to 40 mm for lag screw
applications. Usually, as screw size increases, so does plate thickness. Three-dimensional
plates are available in mini and micro sizes. These plates have added strength due to a
lattice design (9).
Plating systems are sometimes designated as to their proposed function, such as maxillary
miniplates or mandibular miniplates. Although screw dimensions may be the same,
mandibular miniplates are thicker than maxillary miniplates. Mandibular miniplates are
typically 1 mm thick. Mandibular systems are further delineated as trauma sets or
reconstruction sets, with the reconstruction sets offering the thickest (3 mm or more)
stiffest plates in the greatest lengths and with the largest screws. Condylar prostheses may
be included. Specialty plates also exist that are prebent for orthognathic surgery or with
special configurations useful for microvascular reconstruction of the mandible.
Dynamic compression plates are designed to push fracture fragments together as the
screws are driven. The plate holes are ovoid, and the edges of the hole are slanted. When
the screw is tightened, the head slides down the slant, bringing the bone with it. The plate
hole orientation determines the direction of movement and compression. Standard
dynamic compression plates compress parallel to the plate across the fracture. Eccentric
dynamic compression plates have holes on the end that are oriented to provide angular
compression for the superior border of the mandible.
PRINCIPLES OF SCREW APPLICATION
For a screw placed in bone to serve as a stable fixation point, the threads of the screw
must engage or grip the bone around the drill hole. Factors leading to inherent bone
weakness such as osteoporosis or osteitis are beyond the surgeon's control other than by
avoidance. Adherence to good surgical technique, however, will enhance the stability of
the screw in the bone. The drill hole must match the inner screw shaft diameter. If the
hole is too small, excessive friction and stress will result. This excess can lead to shearing
of the screw head or local bone ischemia and resorption. The screw is held by a
functional sleeve of bone around the drill hole that is the thickness of the screw threads
(Fig. 69.4). This thickness varies from screw to screw but is typically on the order of 0.1
to 1.0 mm. Any imprecision in drilling can lead to reduction of this sleeve of bone and a
larger than desired drill hole. High-speed drill chatter, bent drill bits, drill angulation
change (i.e., hand movement), or continued drilling once the hole is complete can lead to
attrition of the bone around the drill hole. Excessive heat leads to delayed attrition from
osteocyte death. Therefore, ideal drilling is achieved with a sharp straight drill bit, a low-
speed drill, a drill guide, a steady hand, and copious irrigation. The diameter of the drill
bit should match the diameter of the screw shaft without threads, not the diameter with
threads. If a drill bit's diameter matches the screw's outer diameter with threads, then the
screw can be pushed or pulled through the drill hole without turning the screw. This
situation is termed gliding and is desirable only in lag screwing.

FIGURE 69.4. Detail of fixation screw in bone. The
diameter of the hole in the bone matches the inner core
diameter of the screw, not the outer thread diameter of the
screw.



Tapping refers to the cutting of screw threads in the drill hole. Most systems have self-
tapping screws now that have flutes beginning at the tip of the screw and extending
several threads up the screw to allow for the cutting of the bone into a thread pattern.
Residual bone dust from the drilling should be irrigated away from the hole before screw
application. The act of tapping itself creates additional bone dust as the threads are cut.
This material can lead to binding and excessive wear of the threads. The bone dust should
be released by intermittent back turns while tapping and irrigated away. Some systems
require or offer as an option tapping as a separate step. The tap thread must match the
screw threads exactly, and the subsequent screw must be placed carefully to avoid cross-
threading. If inadequate bone exists around the drill hole to hold the screw, then it will
fail to tighten as it is screwed into the bone and will begin to slip. Overtightening of the
screw can lead to microfracture or stripping of the bone threads as well. Because this is a
fairly frequent occurrence, most plating systems contain emergency screws, which are
screws with the same shaft diameter but a greater thread diameter to allow for bone
engagement beyond the stripped portion of the hole. If the emergency screw fails to
engage, then another fixation site must be sought. If the plate has extra holes beyond
what is needed for adequate fixation, the stripped screw or spinner may still be useful.
That screw can be left in to anchor the reduction and plate position until the other screws
are placed. Then it should be removed. A recent advance in screw design eliminates the
need for drilling. The tip of the screw is like a drill bit, and the screw is driven directly
into the bone.
LAG SCREW APPLICATION
A lag screw presses two pieces of bone together by compressing the first piece of bone
between the second piece in which the tip of the screw is engaged and the head of the
screw (Fig. 69.5). In this situation, a hole is drilled relatively perpendicular to a fracture
line traversing the fracture. The hole is double drilled such that the part of the hole on the
screw head side of the fracture matches the diameter of the screw with threads, allowing
the screw to glide or to be pushed through the hole to the fracture. On the other side of
the fracture, the hole diameter is drilled to match the screw shaft diameter without
threads. This allows the screw threads to engage the bone on the other side of the
fracture. As the screw is tightened, the top fragment is compressed between the head of
the screw and the second fragment in which the threads are engaging on the other side of
the fracture. A recent enhancement of this technique has occurred through the
development of a tapered drill bit. This bit allows a single drilling motion to provide a
larger gliding hole on the screw-head side of this fracture and a smaller engaging hole on
the other side of the fracture. Because of the often near-tangential angulation of the screw
relative to the cortical surface, a countersink hole is drilled to allow the screw head to
seat better. Sometimes drilling the countersink hole first facilitates drilling for the lag
screw. The countersink hole should not be too deep or the screw head as it is tightened
will pull through the residual cortex into the marrow space and will not be stable.

FIGURE 69.5. A: Drilling gliding hole for lag screw
placement. The diameter matches the outer screw thread
diameter. B: Drilling biting hole for lag screw placement.
The drill bit diameter matches the inner core diameter of
screw. C: Detail of lag screw. Diameter of bone hole
closest to the head of the screw matches the outer
diameter of the threads of the screw, allowing the screw
to be pushed through or glide through the first hole
without being turned. Diameter of the hole closest to the tip of the screw matches the
inner core diameter of the screw. When the screw is tightened, the two pieces of bone are
compressed together.



It is very important to distinguish a lag screw from a positioning screw. A positioning
screw is used in very specific circumstances such as fixation of a mandibular sagittal split
osteotomy. There, lag screw compression may overcompress the mandibular
neurovascular bundle or overtorque the condyle. When a position screw is desired, the
drill holes on either side of the fracture or osteotomy are of the screw shaft diameter
without thread. The screw threads then engage the bone on either side, making
compression across the fracture impossible. The bone segments are fixated into position
relative to each other, but a gap exists between them, and there is no compression.
PLATE APPLICATION
A myriad of plate dimensions and shapes exists that conform to multiple anatomic
applications (10) (Table 69.1). The variety allows the surgeon to maximize the number of
fixation points in solid bone while minimizing potential injury to underlying structures
and working through sometimes difficult exposures. At least two fixation points, one on
either side of a fracture, are required for a plate to function as a tension band (resisting
distraction forces only). However, there is no rotational stability with two points of
fixation. Three points of fixation, two screws on one side of the fracture and one on the
other, will prevent plate rotation. However, the fragment with only one point of fixation
would still have rotational instability. Four points of fixation, two on either side of the
fracture, should be the minimum goal for providing stability of the plate and both
fragments. Additional fixation points up to five or six on either side of the fracture may
be desirable when bony defects are bridged or healing complications are present.
Compression or loading of the bony segments across a fracture, as mentioned before,
increases stability. This compression can be provided before plate application by
compression forceps or by the plate itself.

TABLE 69.1. RECOMMENDED PLATE
APPLICATIONS



INSTRUMENTATION
Application of plates and screws to bone requires specialized instrumentation. Typically,
plating systems are self-contained in that they require all the specialized instrumentation
needed for application of the plates. Standard instrumentation for obtaining exposure of
the fracture site, however, is not included. Scalpels, scissors, clamps, retractors, and
periosteal elevators typically must be supplied in addition to the plating set.
The plating set itself has drill bits that are precisely matched to the screw size. As
previously mentioned, a hole that is too large will prevent the screw from engaging the
bone. A hole that is too small may prevent adequate driving of the screw or, in the case of
microsystems, cause shearing of the head off of the screw shaft as it is being driven.
Typically, there is only one appropriate drill bit diameter for a given screw diameter, and
it is usually the size of the screw shaft (i.e., the screw without its threads). An exception
to this is found in some microplating systems where drill bits of two different diameters
are appropriate for one particular screw diameter. The larger drill bit is used in areas
where the bone is harder and thicker to reduce screw head shearing. A smaller bit is used
where the bone is thinner or softer, particularly in pediatric cases, to increase screw
thread hold. Drill bits with stop collars allow for drilling of a hole to a predetermined
depth. The collar prevents overpenetration of the bit, protecting underlying structures.
Drill guides serve several purposes. They protect the surrounding soft tissue from injury
by the rotating drill bit and allow for percutaneous drilling. The guide also serves to
stabilize the rotating bit, allowing a more precise drill hole. Additionally, guides provide
for more precise placement of a drill hole relative to a plate hole. Concentric drill guides
place the drill hole in the center of the plate hole. Eccentric guides place the drill hole off
center, allowing for compression as the screw head seats in the center of the plate hole. A
recent addition is a guide with a curved extension that points to the drill bit exit site for
through and through drilling. This extension allows more predictable drilling.
Depth gauges allow precise selection of an appropriate screw length for a given
application. When bicortical fixation screws or lag screws are placed, the screw should be
long enough to engage the inner cortex without protruding more than a millimeter or two
beyond the cortex. When monocortical screws are being placed, the surgeon should have
a general idea of the appropriate depth before drilling to avoid damage to underlying
structures before a screw is ever placed. For example, monocortical screws being placed
over tooth roots should not be longer than 3 to 5 mm depending on location, and the drill
hole should not be drilled any deeper than this. Drill bits with collared stops predetermine
the drill hole depth and allow appropriate screw length selection without a depth gauge.
When tapping is a separate step, the depth gauge should be used before tapping to avoid
damage to the threads in the bone.
Some systems contain bone reduction forceps that allow fracture reduction and/or
temporary fixation while plates are being bent and applied. Some of these devices are
designed to apply compression across the fracture. These devices are useful because they
make it possible to avoid having to continually re-reduce the fracture for testing of plate
contour, which may result in a less precise final reduction and fixation. The bulkier
devices require an extraoral approach. Towel, Kelley, or Kocher clamps often will
suffice. Drilling of small holes flanking a fracture will sometimes improve the purchase
of reduction clamps.
Various screwdriver tip and screw head configurations exist, and the interface between
the two is the important factor. Ideally, the interface provides sufficient strength (i.e.,
resistance to stripping) so that appropriate torque can be applied to drive the screw into
the bone. The interface should also allow retention of the screw on the tip of the driver
while it is being brought into position. This retention is achieved in several ways. One is
through friction at the interface. The other is for a clamping mechanism that slides down
the screwdriver shaft and grips the edges of the screw head. This clamp device can be too
bulky for working through percutaneous instrumentation and in other tight locations.
Bone wax on the tip of the screwdriver is a third option when the clamp is too bulky and
interface friction is inadequate for screw retention. Additionally, the interface affects how
quickly the screw can be mounted on the driver, an important factor in dealing with
multiple fractures and long repair procedures. It is also important to know what screw
type is present when removing hardware so the appropriate screwdriver can be available.
Some manufacturers now have screwdriver sets containing all of the common types.
FRACTURE REDUCTION
The structure of the facial skeleton can be viewed as a lattice framework of thick bony
buttresses that impart the three-dimensional strength necessary to withstand the
functional forces of mastication (Fig. 69.6). The intervening thin bone adds little
additional strength but serves as a partition separating various facial components such as
the sinuses, orbits, pharynx, and nasal and cranial cavities. Reestablishment of the
anatomic position and continuity of these buttresses is the key to fracture reduction (11).
Although of secondary importance, anatomic reduction of the intervening thin bone
should be obtained as well, particularly when that bone forms one of the walls of the
orbit. Otherwise, orbital contents will sag through the defect into an adjacent cavity,
resulting in globe malposition.

FIGURE 69.6. A: Facial skeleton showing bony
buttresses with removal of intervening bone. B:
Representation of structural buttressing of the midface.
(Redrawn by Tony Pazos from Chapter 71.)



Anatomic reduction predisposes a frame of reference that guides the replacement of a
malaligned bony fragment into an aligned position. With massive facial trauma, anatomic
reference points may be further away and more difficult to expose. For example, in a
simple zygomaticomaxillary complex fracture, the medial aspect of the infraorbital rim,
the superior aspect of the lateral orbital rim, and the posterior maxillomalar buttress
provide adequate reference points for anatomic reduction. Panfacial fractures resulting in
comminution or mobility of these reference points may necessitate exposure of the root
of the zygomatic arch as another reference point for appropriate placement of the
zygomaticomaxillary complex (12). Intraoperative three-dimensional positioning systems
offer some promise in aiding with this problem.
High-energy injuries may lead to severe comminution or even pulverization of
intervening segments of bone. In this case, bony structure is reduced to its anatomic
position based on existing reference points, and intervening gaps in the buttresses are
bone grafted. Reestablishing bony continuity of the buttresses is imperative because they
must ultimately transmit the forces of mastication to the skull base. Sometimes a bony
fragment from a less crucial area can be borrowed and reoriented to establish buttress
continuity. Frequently, additional bone is required, however, and outer table calvaria is
our preferred source for bone grafting because of its reliability and proximity to the injury
site (Fig. 69.7). Minimal donor site morbidity and frequent preexisting exposure due to
use of the bicoronal approach to the face are benefits. Other relatively popular donor sites
include the ilium and ribs. Hydroxyapatite cement offers promise for dealing with bony
defects without attendant donor site morbidity.

FIGURE 69.7. In situ technique of outer table calvarial
bone harvest. A: Location of donor site on parietal skull.
B: Saucerization of bone around graft. C: Cross-
sectioned view of saucerization. D: Calvarium split with
angled saw. E: Calvarium split with reciprocating saw.



OCCLUSION
For the masticatory apparatus to function properly, stable reproducible occlusion must
exist. For occlusion to occur, the cusps of the maxillary dentition must fit into the
grooves of the mandibular dentition and vice versa (Fig. 69.8). This is termed
intercuspation. Wear facets of opposing teeth should contact each other. The wear
patterns may be the only reference when preinjury occlusion is abnormal. Normal molar
occlusion in the anterior-posterior dimension is defined as intercuspation of the mesial
buccal cusp of the maxillary first molar with the buccal groove of the mandibular first
molar. This description does not address transverse molar relationships or anterior dental
relationships. A normal transverse relationship exists when the buccal cusps of the
mandibular molars are between the buccal and palatal cusps of the maxillary molars.
Normal anterior dental relationship occurs when the maxillary anterior dentition is 1 to 3
mm anterior to the mandibular anterior dentition with central incisal overlap of 1 to 3
mm. Increased distance horizontally between the incisors is overjet. Increased vertical
distance is overbite or deep bite. Anterior crossbite and anterior open bite are the
respective converse conditions.

FIGURE 69.8. A: Various anterior incisal relationships.
1, Normal; 2, overjet and overbite; 3, edge to edge; 4,
anterior crossbite or underbite; 5, anterior open bite. B:
Transverse relationships. 1, Normal; 2, bilateral lingual
crossbite; 3, bilateral buccal crossbite; 4, unilateral
lingual crossbite. C: Sagittal molar class relationships. 1,
Class I; 2, class II, division I; 3, class II, division II; 4,
class III.



Because preinjury occlusion is frequently not normal as defined above, it is useful to
question the patient or family about the preinjury occlusion. Dental records are also quite
helpful. In the absence of this information, wear facets are the main occlusal guide. When
the preinjury occlusion is unclear, then anatomic reduction of the fractures before
interdental fixation may be more accurate. There should be no reluctance to open
interdental fixation if it is preventing anatomic reduction of bone segments. The
interdental fixation and skeletal reduction should correlate. If they do not, a preexisting
malocclusion should be suspected.
INCISIONS AND EXPOSURE
Adequate anatomic reduction requires wide exposure to view fractures from several
angles. Lacerations may provide some exposure, but frequently more is needed. The
entire craniofacial skeleton can be exposed through a combination of hidden or well-
camouflaged incisions (13) (Fig. 69.9). The entire mandible except for the condyles can
be exposed through intraoral vestibular sulcus incisions (14) (Fig. 69.10). Small stab
incisions through the cheek may be necessary for plating posterior fractures; however,
angulated instrumentation promises to reduce the need for even these incisions. Pitfalls
associated with the mandibular vestibular sulcus incision include damaging the mental
nerve, failure to achieve a watertight closure of the incision, and failure to resuspend the
mentalis muscle if the chin is degloved. Intraoral incisions for the mandible are not
recommended with comminuted fractures, severe periodontal disease, or hygiene
problems. Because of the tangential view achieved when approaching posterior fractures
transorally, it can be very difficult to contour a heavy plate to the outer cortex. It is our
recommendation that any situation requiring a heavy plate placed posteriorly on the
mandible should be approached extraorally through a Risdon and/or submandibular neck
incision. Low subcondylar fractures needing repair can be approached transorally, but
this requires specialized equipment. High subcondylar fractures needing repair are best
approached either through a Risdon or a preauricular incision (15).

FIGURE 69.9. A: Cranioorbital exposure through
bicoronal flap. B: Midface exposure through
circumvestibular incision. (Redrawn by Tony Pazos from
Chapter 71.)



FIGURE 69.10. A: Intraoral approach to the anterior
mandible. B: Intraoral approach to the angle of the
mandible.



The inferior maxilla can be exposed through a superior circumvestibular incision. The
superior exposure can be extended by elevating the nasal floor mucosa between the
inferior turbinate root and maxillary crest. Even further superior exposure can be
obtained by incising the nasal mucosa along the cephalic border of the lower lateral
cartilage and piriform aperture in a full midface degloving approach. Pitfalls include
damage to the infraorbital nerve, nostril stenosis, and leaving inadequate oral vestibular
mucosa for wound closure.
Upper facial access can be obtained through a bicoronal incision elevated in the subgaleal
or subperiosteal plane. This incision provides access to the medial, superior, and lateral
walls of the orbit; the zygomatic arch; and the bony pyramid of the nose. It additionally
uncovers donor sites for cranial bone grafting. Pitfalls include damage to the frontalis
innervation and inadequate closure of the galea, both leading to brow ptosis.
Infraorbital rim and orbital floor exposure is still limited, however, and a lower lid
incision is required for that exposure. We prefer either a subciliary incision or a
transconjunctival incision with or without a lateral canthotomy for the increased exposure
when necessary. Inferior lid crease and rim incisions are other options in this area.
Careful closure of these incisions and canthopexy are critical to reduce lid complications
of entropion or ectropion.
If a bicoronal incision is not performed, then access to the frontozygomatic region can be
obtained through a lateral brow incision or a superior lid crease incision. Medial orbital
wall and nasoethmoid exposure can be obtained through a gull-wing or external ethmoid-
type incision. If the nasal dorsal skin between the incisions is sufficiently elevated and
mobilized, then adequate exposure can usually be obtained by retracting the skin without
having to make the transverse incision across the nasal dorsum.
APPROACH TO PANFACIAL FRACTURES
Severe and complex facial disruptions represent difficult challenges for the
craniomaxillofacial surgeon, because usually few reference points are available to help
the surgeon determine how to reposition the multiply fractured fragments. Nonetheless,
the principles of repair remain the same, and careful attention to the procedures described
previously will lead to the best possible outcomes.
Emergencies related to massive facial trauma must be attended to first (Table 69.2). The
airway can be threatened by anatomic obstruction, blood, or both and must be secured.
Gross hemorrhage must be controlled, preferably with direct pressure. Definitive control
should be obtained in the operating room to prevent damage to important nonvascular
structures. Occasionally, partial reduction of severely displaced fractures is necessary to
aid in the control of hemorrhage. A few interdental wires can be placed emergently to
stabilize this gross reduction and alleviate some of the pain associated with mobility of
the fractures. Soft-tissue injuries should be irrigated and repaired if the patient is not
planned for immediate fracture repair in the operating room. Dental avulsions and
fractures through the pulp cavity should be treated urgently if the damaged teeth are to be
salvaged. Preoperative antibiotics have been shown to reduce infectious complications
(16).

TABLE 69.2. EMERGENCIES FACIAL
TRAUMA



History and physical examination can provide some initial indication of the extent of
facial injuries. Historical information such as mechanism of injury and energy of impact
is useful in assessing the extent of the injury. Ecchymosis patterns including raccoon eyes
and Battles sign can be indicative of skull base fractures. Other soft-tissue findings such
as the bowstring lid test can indicate canthal detachments. Palpation of bone surfaces will
allow detection of step-offs and mobility. Documentation of cranial nerve function is
critical to distinguish injury-associated deficits from iatrogenic deficits occurring after
fracture repair. Other factors such as neurologic and visual function are frequently
impaired with panfacial fractures. Neurologic and ophthalmologic assessment are
necessary (17).
Radiologic evaluation is key to the full assessment of massive facial trauma (18). In our
institution, axial computed tomography is obtained as part of the initial trauma protocol
when head and facial injuries are present. Because of cervical spine clearance issues,
acute direct coronal computed tomographies are rarely obtained. If complex periorbital
fractures are present, then when the patient's condition permits, direct coronal computed
tomography is obtained. The mandible is separately evaluated with plain radiographs and
panoramic radiography if the patient's condition permits. Rarely, with severe injury,
three-dimensional reconstructions are used.
With severe craniofacial injuries, there is a high risk that injuries may involve the eyes,
dura, and neural structures of the skull base and cervical spine. It is essential that the
surgeon is attuned to these possibilities, because failure to recognize these associated
injuries could have dire consequences for the patient. Globe injuries must be evaluated by
ophthalmology. Ruptured globes often require enucleation, though occasionally minor
ruptures may be repaired, and this situation may mandate a postponement of the repair of
the orbital/periorbital fractures. Similarly, a retinal detachment may require a period of
healing before surgical manipulation of the surrounding bones.
It is critically important to identify optic nerve compression, because rapid and
aggressive management of this injury may preserve or even salvage vision. When optic
nerve compression is associated with frontonasal fractures of the anterior skull base, the
subcranial approach as advocated by Raveh et al. (19) provides excellent access to the
optic nerve canal(s) for decompression. In the subcranial approach, the nasal bones and
front wall of the frontal sinus are removed en bloc and saved for later replacement. The
posterior wall is then opened, allowing full visualization of the anterior cranial fossa
without olfactory compromise or significant brain retraction. This approach also allows
for the repair of associated skeletal injuries in the anterior skull base, medial orbits,
frontal area, and nose. Rigid fixation allows for the dependable repositioning of the bone
fragments and thereby makes the subcranial approach possible. Without rigid repair of
the completely removed nasofrontal bone fragments, there would be a high probability of
malposition and/or resorption of the bone. Most authors advocate a trial of very high-dose
steroids before optic nerve decompression is attempted (20). An eye that shows no light
perception from the moment of impact is probably irretrievable, and the value of
decompression in this situation is controversial at best. On the other hand, if a patient has
progressive visual loss or if a seeing eye progresses to no light perception after trauma to
the area of the posterior orbit and/or anterior skull base and if steroids are not effective in
restoring vision within 24 to 48 hours, then most authors would agree that the potential
benefit of optic nerve decompression probably outweighs the risks. If the subcranial
approach is not appropriate (or desired), then the optic canal can be approached
endoscopically through the sinuses or from above via an intracranial approach (21).
When the floor of the anterior fossa is disrupted, then it is convenient to perform the
repair at the time of facial fracture reduction. Here again, the subcranial approach
provides excellent access to this area. It allows for repair of the anterior fossa with a
fascial patch or a pericranial flap, without the need to significantly elevate or retract the
frontal lobes. This is a very desirable feature of the technique. Because in most of these
panfacial fracture cases the brain has been injured and is likely to be swollen, acute repair
should decrease the likelihood of cerebrospinal fluid leakage and thereby decrease the
risk of later development of meningitis.
With regard to timing of repair of fractures, unless a patient's overall condition prevents
it, immediate repair is the best approach (22). Immediate repair allows visualization of
facial structures before the full development of injury edema, which generally occurs 24
to 48 hours after the injury. Neurologic injury in patients may require several days for
stabilization (23). Delaying repair leads to increased bacterial contamination and risks of
infection. With further delay, the soft-tissue envelope around the fractured skeleton
begins to fibrose and contract, increasing resistance to anatomic reduction. Callous
formation and resorption of some of the fine detail of the fracture edges increases the
difficulty of mobilization and reduces the ability to achieve an accurate reduction.
As previously stated, one of the major problems with massive facial trauma is a lack of
reference points for anatomic reduction. Approaches yielding wide exposure are
preferred (24). With maximal exposure of the facial skeleton, repair should begin at the
periphery, including recreating the contours of the skull and the mandible. The ultimate
reference for facial skeletal position is the skull base (Fig. 69.11). For the mandible, this
reference is through the condyles. For the middle and upper face, the reference points are
the lateral and medial orbital rims, the nasal radix, the piriform apertures, and the
posterior maxillary buttresses. Anterior skull fractures can obscure some of these
reference points, but then the next higher point of skeletal stability becomes the new
reference point. Once anterior skull fractures are repaired, facial fracture repair can
proceed. A systematic approach working from areas of stability toward areas of
instability is required. All fractures that are to be repaired should be exposed and reduced
before any final fixation. Vertical, horizontal, and sagittal facial dimensions must be
restored (Fig. 69.12). We often prereduce complex fractures with wires or sutures
initially, withholding more rigid fixation until all fractures have been adequately reduced.
Maxillomandibular interdental fixation should be achieved before skeletal fixation as
well. Release of maxillomandibular fixation may be required to effect anatomic reduction
of bony segments, particularly when preinjury occlusion does not appear to have been
normal. Cutting an arch bar over an area where a fracture proceeds between teeth may
also be required to achieve anatomic bony reduction. The split arch bar is then repaired
once reduction is obtained.

FIGURE 69.11. Skull base detail showing major areas of
attachment of the facial skeleton to the cranial skeleton.
These include the nasal and zygomatic processes of the
frontal bone, the zygomatic process of the temporal bone,
the nasal septum, and the pterygomaxillary junction.



FIGURE 69.12. Important dimensions of the facial
skeleton to be reestablished during reconstructive efforts.



Typically, fracture fixation proceeds centripetally toward the nasal region (Fig. 69.13).
Skull fractures, frontal sinus fractures, and any intracranial injuries are addressed first. A
subcranial approach as previously mentioned through the nasofrontal region is our
preferred method to access the anterior cranial fossa and medial orbits. The mandible
should be repaired, and if necessary defects should be bridged with reconstruction plates.
Whether the mandible is severely comminuted or partially absent, the occlusal
relationship remains the priority concern and the best indication of the premorbid shape.
When the dentition is lost or absent, occlusion becomes less critical and obviously
unusable as a landmark. Mandibular height should be reconstituted, using a
costochondral graft to reestablish the condylar position if the condylar head has been lost.
In the case of bilateral displaced subcondylar fractures and midface fractures, at least one
of the subcondylar fractures will need to be opened and internally fixated to provide a
reference for lower third facial height. If necessary, zygomatic arch fractures are then
fixated to provide an anterior-posterior reference for the malar eminence (25). In rare
cases, this may require bone grafting of one or both malar eminences to reestablish the
proper facial projection. The maxilla and its dentition can then be suspended rigidly from
the zygomas, using plates and/or bone grafts to ensure fixation and bony continuity.
Posterior maxillary buttress, piriform aperture, and lateral orbital rim fractures are then
repaired. Then the orbital rim contours are reconstructed, trying to recreate the natural
shape of the orbits with bone grafts while at the same time making sure that the globes
are returned to their proper position with a 2- to 3-mm overcorrection to allow
retropositioning as swelling decreases. Any buttresses with segmental defects after
appropriate reduction of the skeletal structures are bone grafted. The bone grafts are
stabilized and positioned with bridging plates and/or screws. Once buttress continuity has
been reestablished, thickening lamellar bone defects are addressed as needed. The
bimalar diameter can usually be reestablished based on the posterior buttresses after
occlusal relationships have been reestablished. With severe comminution, however,
repair of the nasoethmoidal complex provides additional reference information for
restoration of the bimalar diameter.

FIGURE 69.13. A: Panfacial fractures. B: Repair of
fractures with rigid fixation. Fractures are typically
repaired centripetally, working from the skull base and
the mandible toward the midface and working from the
lateral midface toward the medial midface.



Orbital floor continuity must be reestablished. We prefer autogenous bone for this repair,
and alloplastic implants are not advocated for this location, though this is clearly a
controversial issue. Perpendicular plate of ethmoid, if not severely fractured, can be used
to replace the orbital floor, walls, or roof. Cranial bone or the nonfractured anterior face
of the maxilla also do well here. Very small defects can be covered with gelatin film or
homograft dura. The superior, medial, and lateral orbital walls need to be repaired if they
are displaced enough to impinge on orbital contents or significantly alter orbital volume.
A defect greater than 2 to 3 cm in diameter of the anterior face of the maxilla itself may
need to be repaired; otherwise, facial soft tissue will collapse into the sinus, creating a
subtle but noticeable deformity of the melolabial region.
Finally, the nasoethmoid complex is addressed. The typical telescoping collapse must be
reduced and reprojected. Frequently, the lamina papyracea needs to be replaced with
bone grafts to support forward projection and prevent the herniation of periorbita into the
ethmoid sinuses. The projection of the nose is reestablished by cantilevering off the
frontal bone and/or fixation of the medial orbital region. If the nasal dorsum is deficient,
a primary bone graft should be placed.
Once complete fracture reduction has been achieved, certain soft-tissue structures that
were detached traumatically or to provide exposure must be resuspended. The medial and
lateral canthi should be suspended from the adjacent bone slightly posterior and superior
to their original insertion sites either with wires or heavy nonabsorbable sutures. For
medial canthal suspension, a permanent suture is placed through the medial canthal
ligament. The suture is passed through the nasal septum, lamina papyracea, and/or drill
holes in the medial orbital wall bone grafts, positioning it so that the ligament is pulled
posteriorly and superiorly. The medial tension is then adjusted using the suture, which is
fixed to opposite frontal bone using a plate hole, a screw, or a hole drilled through the
medial supraorbital rim. The mentalis muscle, as previously mentioned, should be
suspended from drill holes in the menton. The lacrimal ducts should be cannulated if they
do not flow freely when irrigated. Access incisions must be closed meticulously to
prevent complications. Failure to close the galea in the bicoronal incision can lead to
brow ptosis. Failure to obtain watertight closure of intraoral incisions can lead to
dehiscence and plate exposure. Particular attention should be paid to the lower lid
incision closure to prevent entropion or ectropion.
SOFT-TISSUE LOSS
The acute repair of soft-tissue loss remains controversial when dealing with facial
injuries. Of course, whenever it is feasible, it is preferable to repair soft-tissue loss and
bone loss simultaneously. In years past, early attention was directed at restoring the soft
tissues, with the belief that the primary repair of the facial skeleton could not be
successfully performed in the absence of adequate soft-tissue coverage. Unfortunately, in
the absence of proper skeletal support, reconstructed soft tissues often shrank and
retracted, leading to the development of contractures that frequently interfered with the
ultimate hard-tissue reconstruction, and a satisfactory outcome was less likely to result.
The advent of rigid skeletal fixation has allowed for a rethinking of this approach,
because rigidly fixed bony structures will generally survive even in the absence of
adequate soft-tissue coverage. This has proved particularly helpful in shotgun-blast
injuries, which can be very destructive to both skeletal and soft tissues. An example is
shown of the case of a stainless steel mandibular reconstruction plate that was placed
across a shotgun-blast defect of the anterior mandible (Fig. 69.14). The defect extended
from midbody to midbody. Deltopectoral skin was used to incompletely cover the steel
plate. (Note that this approach could not have been considered before the introduction of
rigid fixation techniques, because mobile exposed bone fragments often become infected
and necrosed.) Ultimately, after release of the flap and closure of the soft-tissue defect,
the space (which had been maintained by the reconstruction plate) was reconstructed with
an iliac corticocancellous graft that was fixed to the plate. The graft took completely, and
the plate was later removed, leaving fully recontoured mandible.

FIGURE 69.14. A: Patient with midfacial shotgun-blast
injury after soft-tissue repair. B: Initial maintenance of
mandibular spacing with reconstruction plate. C: Bony
continuity reestablished with graft, and plate is removed.
D: Result after additional soft-tissue surgery.



The same principles have been similarly applied to midfacial defects. The availability of
microvascular free tissue transfer has made it possible to perform immediate soft-tissue
and/or skeletal reconstruction of large defects when the patient's condition is appropriate.
Restoration of the skeletal framework (or its shape) should be accomplished as acutely as
possible. Though the soft-tissue reconstruction is now generally performed acutely when
possible, it can be delayed if necessary due to the needs of the individual patient and/or
the techniques available for repair.
COMPLICATIONS AND REVISIONS
With severe injuries, it is not uncommon to obtain a less than perfect result, though an
excellent reconstruction is often acceptable to patients who appreciate the severity of
their initial injuries. Still, selective revision surgery can enhance an outcome and convert
an acceptable result to an excellent one. The judicious use of bone grafts or alloplastic
implants may be necessary to build up deficient areas or reposition a globe. Occasionally,
a malunion may result, and one of the options available is the remobilization of facial
bones via osteotomy followed by repositioning and refixation with bone grafts as needed.
The techniques for this are beyond the scope of this chapter, but it is important to offer
this option to a patient with a residual deformity.
It is not uncommon for craniomaxillofacial surgeons in tertiary care centers to receive
referrals of patients who have already undergone initial and sometimes subsequent
repairs. Occasionally, patients have not been repaired at all for a variety of reasons. It is
important for the tertiary surgeon to avoid judgmental commentary and focus on what
can be offered to the patient. These are challenging cases both technically and
emotionally, and they should be approached with the utmost skill and diplomacy.
A host of complications may be seen, including ectropion, entropion, facial scarring,
epiphora, numbness, facial nerve injuries, diplopia, malocclusion, facial asymmetry, and
temporomandibular joint dysfunction (Table 69.3). Familiarity with the multiplicity of
problems and outcomes that can result will make it possible for the facial plastic surgeon
to offer the patient the widest variety of options for care.

TABLE 69.3. COMPLICATIONS FACIAL
TRAUMA




HIGHLIGHTS
Management of massive or complex injuries follows the same
principles used for less severe injuries.
Anatomic reduction of fractures offers the best chance of return
to preinjury function and appearance.
Rigid internal fixation stabilizes and shields a reduced fracture
from biomechanical forces that would act to displace the
fracture until bone healing can occur.
Fracture repair is best achieved as early after the injury as
possible with the following being considered: the patient's
overall condition takes priority and maximal soft-tissue
swelling occurs 24 to 48 hours after the injury.
Within limits, the stability of an internal fixation system
increases with the rigidity and thickness of the material, the size
and number of screws, the thickness of the underlying bone,
and compression of the fracture edges.
Application of a screw to be a successful fixation point for a
plate requires maintenance of a healthy cylinder of bone lining
the drill hole that hugs the inner shaft of the screw as it or a
tap cuts threads in the bone.
Plate type and location selection is made to provide adequate
stability to a fracture while minimizing application difficulty,
hardware load, and prominence through the soft tissue.
The three-dimensional skeletal buttress structure and continuity
must be reestablished to restore facial appearance and the
ability to withstand biomechanical forces.
Resuspension of key soft-tissue structures such as the medial
and lateral canthi and the mentalis muscle is necessary to obtain
the best result from treatment of massive trauma.
Minor complications are not uncommon and can usually be
managed with minor revisions. Major complications from tissue
loss or malposition are best prevented, but major reconstructive
procedures with osteotomies and bone grafting can provide
satisfactory final results.
CHAPTER REFERENCES
1. DeLacure MD. Physiology of bone healing and bone grafts. Otolaryngol Clin North Am
1994;27:859874.
2. Manson PN. Facial bone healing and bone grafts: a review of clinical physiology. Clin Plast Surg
1994;21:331348.
3. Phillips JH, Rabin BA. Bone healing. In: Yaremchuk MJ, Gruss JS, Manson PN, eds. Rigid
fixation of the craniomaxillofacial skeleton. Boston: Butterworth-Heinemann, 1992.
4. Alpert B. Complications in mandibular fracture treatment. Probl Plast Reconstr Surg 1991;1:253
289.
5. Kendrick RW. Management of gunshot wounds and other urban war injuries. Oral Maxillofac
Surg Clin North Am 1990;2:5568.
6. David DJ, Simpson DA, eds. Craniomaxillofacial trauma. New York: Churchill Livingstone,
1995.
7. Prein J, Kellman RM. Rigid internal fixation of mandibular fractures: basics of AO technique.
Otolaryngol Clin North Am 1987;20:441456.
8. Valentino J, Levy FE, Marentette LJ. Intraoral monocortical miniplating of mandible fractures.
Arch Otolaryngol Head Neck Surg 1994;120:605612.
9. Kellman RM. Recent advances in facial plating techniques. Facial Plast Surg Clin North Am
1995;3:227239.
10. Kellman RM, Marentette LJ. Atlas of craniomaxillofacial fixation. New York: Raven Press, 1995.
11. Mathog RH. Atlas of craniofacial trauma. Philadelphia: W.B. Saunders, 1992.
12. Stanley RB. Current approaches to LeFort and zygomatic fractures. Facial Plast Surg Clin North
Am 1995;3:97105.
13. Shumrick KA, Kersten RC, Kulwin DR, et al. Extended access/internal approaches for the
management of facial trauma. Arch Otolaryngol Head Neck Surg 1992;118:11051112.
14. Dierks EJ. Transoral approach to fractures of the mandible. Laryngoscope 1987;97:46.
15. Klotch DW, Lundy LB. Condylar neck fractures of the mandible. Otolaryngol Clin North Am
1991;24:181194.
16. Chole RA, Yee J. Antibiotic prophylaxis for facial fractures: a prospective, randomized clinical
trial. Arch Otolaryngol Head Neck Surg 1987;113:10551057.
17. Gupta LY, Levin PS. Ophthalmic consequences of orbital trauma. Oral Maxillofac Surg Clin
North Am 1993;5:443455.
18. Manson PN. Dimensional analysis of the facial skeleton: avoiding complications in the
management of facial fractures by improved organization of treatment based on CT scans. Prob
Plast Reconstr Surg 1991;1:213237.
19. Ladrach K, Annino DJ, Raveh J, et al. Advanced approaches to cranio-orbital injuries. Facial
Plast Surg Clin North Am 1995;3:107130.
20. Anderson RL, Panje WR, Gross CE. Optic nerve blindness following blunt forehead trauma.
Ophthalmology 1982;89:L445L455.
21. Joseph MP, Lessell S, Rizzo J, et al. Extracranial optic nerve decompression for traumatic optic
neuropathy. Arch Ophthalmol 1990;108:10911093.
22. Wenig BL. Management of panfacial fractures. Otolaryngol Clin North Am 1991;24:93101.
23. Derdyn C, Persing JA, Broaddus EC, et al. Craniofacial trauma: an assessment of risk related to
timing of surgery. Plast Reconstr Surg 1990;86:238245.
24. Haug RH, Buchbinder D. Incisions for access to craniomaxillofacial fractures. Atlas Oral
Maxillofac Surg Clin North Am 1993;1:129.
25. Gruss JS, Van Wyck L, Phillips JH, et al. The importance of the zygomatic arch in complex
midfacial fracture repair and correction of posttraumatic orbitozygomatic deformities. Plast
Reconstr Surg 1990;85:878890.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

70 PEDIATRIC OTOLARYNGOLOGY
Head & Neck SurgeryOtolaryngology
70




PEDIATRIC OTOLARYNGOLOGY
MICHAEL J. CUNNINGHAM
LEILA A. MANKARIOUS

M.J. Cunningham and L.A. Mankarious: Department of Otolaryngology, Massachusetts Eye and Ear
Infirmary, Boston, Massachusetts.


Patterns of Growth and Development
Congenital Malformations
Auricular Malformations
Nares Malformations
Midline Malformations
Malformations of the Oral Cavity
Airway Abnormalities
Malformations of the Neck
Sensory Impairments
Infectious Diseases
Otitis Media
Rhinosinusitis
Cystic Fibrosis
Adenotonsillar Surgery
Special Issues
Conclusion
Chapter References
The management of the otolaryngologic disorders of childhood traditionally has been and
remains an integral part of the practice of general otolaryngology. In the past 20 years,
however, a subspecialty interest group oriented toward the comprehensive
otolaryngologic care specifically of children has grown within otolaryngology.
The historical roots of this subspecialty can be traced to developments within the fields of
pediatrics and anesthesia and within otolaryngology itself. The establishment of free-
standing children's hospitals or sections of general hospitals devoted solely to pediatric
care reflected a growing appreciation on the part of the medical community that the
problems of children differ from those of adults and require a different focus of
diagnostic intervention and management. The patient population of these children's
hospitals and pediatric wards changed over the years as the development of vaccines and
newer generations of antibiotics led to improved control of acute infectious diseases. The
focus of pediatric medicine gradually shifted to children with chronic illnesses,
progressive noninfectious disorders, malignancies, and disabling or disfiguring
handicaps. Patients with these much more complex conditions required the coordinated
services of many subspecialty fields, including otolaryngology.
Concurrent technologic advances and a better understanding of the pathophysiologic
characteristics of cardiorespiratory failure ushered in the modern era of anesthesia and
intensive care unit medicine. The establishment of pediatric and neonatal intensive care
units, the latter associated with advanced obstetric care hospitals, allowed the treatment
and survival of younger and sicker infants and children. These children presented a new
array of medical and surgical problems of interest to the otolaryngologist, particularly
regarding airway management.
Scientific advances within the field of otolaryngologyhead and neck surgery further
contributed to pediatric subspecialization. The development of fiberoptic illuminated
rigid endoscopes of appropriate size for use in the infant and pediatric airway allowed
safe operative assessment of congenital and acquired airway lesions. The introduction of
laser therapies, particularly the carbon dioxide laser, provided a precise surgical tool for
use in treating such lesions. Newer laryngoscopes and subglottoscopes were developed to
allow unrestricted visualization of the pediatric airway for instrumentation and laser
applications and to facilitate the delivery of inhalational anesthetic agents through
standard endotracheal, Venturi jet, or spontaneous respiration techniques. Small-diameter
flexible endoscopes facilitated the dynamic examination of the upper airway in awake
infants and children, and ultrathin versions of these scopes allowed lower airway
evaluations even in intubated infants.
Radiologic advances in computed tomography (CT), magnetic resonance imaging (MRI),
and digital subtraction angiography added to the diagnostic acumen available for
evaluating both congenital malformations and mass lesions. The application to children
of angiographic embolization and microvascular surgical techniques, more precise
radiotherapyincluding proton beamprotocols, and newer chemotherapeutic agents
greatly influenced the management of aggressive, benign, and malignant head and neck
neoplasms in this age group.
Polysomnography studies enhanced the physiologic assessment of children with
obstructive lymphoid hypertrophy. Immunologic antibody-antigen detection techniques
facilitated the serologic diagnosis of various infections and the confirmation of inhalant
atopy in young children. Electrodiagnostic techniques such as electroneurography,
electromyography, brainstem auditory-evoked response testing, and otoacoustic
emissions allowed more in-depth assessment of pediatric sensory impairments. Cochlear
implantation for children has opened new avenues of therapeutic intervention, and soon
brainstem implantation may become a viable advance in the treatment of sensorineural
hearing loss.
The application of these technical innovations to the care of children with acute and
chronic otolaryngologic problems stimulated further clinical investigation and bench
research activities, leading to an increasing fund of knowledge and expertise and the
eventual growth of this subspecialty. Pediatric otolaryngology shares with geriatric
otolaryngology a focus on a specific age group rather than in an organ system or category
of disease. This chapter highlights those disorders specific to the pediatric population.
PATTERNS OF GROWTH AND DEVELOPMENT
Pediatric otolaryngology is the study of the disorders and diseases of the ears, nose, and
throat as they relate to the growth and development of the head and neck structures. The
clinical presentation and sequelae of any disease process are greatly influenced by the age
and maturation of the afflicted person. Children not only differ anatomically and
physiologically from adults, but they also change in these respects along a continuum
from the neonatal/infancy period through the toddler, preschool, and later childhood
years and eventually adolescence. Pediatric otolaryngology requires a working
knowledge of the standard patterns of growth and development through these years so
that deviations from normal can be recognized and age-appropriate diagnostic techniques
and methods of management can be applied.
Measurement of the vital characteristics of somatic growth can provide information about
a child's general state of health or illness regardless of the specific organ system of
interest. Height and weight measurements of all children, supplemented by head
circumference measurements during the first year of life, provide an early warning
system for pathologic processes. Charts documenting serial measurements over months to
years construct an accurate record of the child's general pattern of growth (Fig. 70.1 and
Fig. 70.2) with deviations from normal being indicative of an intrinsic or extrinsic insult.

FIGURE 70.1. Physical growth in boys (National Center
for Health Statistics percentiles).



FIGURE 70.2. Physical growth in girls (National Center
for Health Statistics percentiles).



Different organ systems mature at different rates and at different times throughout
infancy, childhood, and adolescence (Fig. 70.3). The rapid rate of neural tissue growth
during fetal life explains the relatively large size of the neurocranium in relation to the
face in the newborn.

FIGURE 70.3. Postnatal growth of different anatomic
systems with age.



The face of the infant or young child is not a small image of the eventual adult (Fig.
70.4). The infant's forehead is prominent and the face comparatively round and
diminutive. Elongation of the face occurs secondary to mandibular and maxillary growth
in association with the eruption first of the primary and later of the permanent teeth. As
this vertical growth continues throughout childhood, the relative proportion of facial to
cranial mass gradually changes, and the more narrow adolescent/adult facies eventually is
achieved (Fig. 70.5). Associated with this progressive increase in facial height is a
gradual change in the child's profile. The child's cheeks and chin are flat, the nose is
diminutive, and the eyes appear comparatively large. With mandibular and maxillary
growth, the chin and cheek bones become more prominent, and the growth of the nose
and supraorbital rims decreases the relative orbital size.

FIGURE 70.4. Changing facial configuration with age.
A: At birth. B: Through 5 years. C: At 15 years. (From
Stool SE, Marasovich W. Postnatal craniofacial growth
and development. In: Bluestone CD, Stool SE, eds.
Pediatric otolaryngology, 2nd ed. Philadelphia: W.B.
Saunders, 1990:18, with permission.)



FIGURE 70.5. Infant and adult skulls for craniofacial
skeletal comparison. A: Lateral views. B:
Anteroposterior views.



The nares are small at birth and retain their roughly circular shape until puberty. The oval
or oblong nares associated with the adult facies develop in association with the marked
increased vertical growth of the nose during adolescence. A major force in the vertical
height and projection of the nose is believed to be the osseous and cartilaginous growth
centers of the nasal septum and lateral nasal wall. Elective surgery on the nose usually is
deferred until the adolescent years when full facial growth has been achieved. Exceptions
to this rule include severe traumatic injuries or congenital anomalies, such as those
associated with cleft lip. Growth may further exaggerate the facial deformity in such
cases.
Despite small anatomic nasal dimensions and increased airway resistance, infants are
predominantly nasal breathers (the anatomic and physiologic explanations for this
preferential nasal breathing pattern are discussed later in this section). Although the
degree and duration of this reliance on the nasal airway for respiration vary with each
child, complete nasal airway obstruction at birth is usually an airway emergency. Even
unilateral obstruction can cause the newborn significant respiratory distress and
secondary feeding difficulties. In older children, chronic nasal and nasopharyngeal
obstruction, most frequently caused by lymphoid hypertrophy, may be associated with
constant mouth breathing, abnormal tongue positioning, and suspected craniofacial
growth changes. This so-called adenoid facies syndrome remains controversial from a
cause and effect standpoint; its description, however, serves to highlight the potential
sequelae of a single disease entity on an actively growing child.
The development of the paranasal sinuses is connected intimately with nasomaxillary and
facial growth (Fig. 70.6). The maxillary and sphenoethmoid sinuses are present at birth,
although their small size typically precludes their radiologic appearance (Table 70.1).
Conspicuous growth in the maxillary sinuses begins by approximately age 3 years, but
inferiorly directed expansion does not occur until eruption of the permanent dentition,
when the child is 7 to 8 years of age. The floor of the maxillary sinus approximates the
inferior meatus at age 8 years and reaches the level of the floor of the nose by 12 years of
age. Adult size is reached by mid-adolescence. This anatomic progression in size has
important implications regarding standard sinus surgical approaches. Inferior transmeatal
antrotomy in children aged under 8 years is difficult, and the transcanine approach risks
injury to the developing tooth buds. When a Caldwell-Luc maxillary antrostomy is
necessary in a child, preoperative radiographs should be used to locate the unerupted
dentition so that the antrostomy cuts can be performed superior and lateral enough to
avoid violating that dentition.

FIGURE 70.6. Paranasal sinus development. A: At birth.
B: At 10 years. C: At 15 years.



TABLE 70.1. PARANASAL SINUS
DEVELOPMENT



The ethmoid sinuses arise as evaginations of the nasal mucosa from the middle, superior,
and supreme nasal meatuses. Although present at birth, significant pneumatization does
not occur until the child is aged between 3 and 7 years. Final adult form typically is
achieved by age 12 to 14 years. The sphenoid sinuses originate within the nasal cupola;
they do not begin to pneumatize the sphenoid bone and become clinically significant until
4 to 5 years of age. Sphenoid development, although complete by mid-adolescence, is
highly variable in terms of the final extent of sphenoid bone pneumatization. The frontal
sinuses originate as outgrowths of the middle meatuses in the frontal recess regions.
Typically not present at birth, growth begins during the third year of life and continues
well into adolescence. Pneumatization is highly variable and is of limited clinical
significance until the early adolescent years. The thin posterior table and floor of the
frontal sinuses have important anatomic relationships to the anterior cranial fossa and
orbital structures, respectively.
A current discussion of paranasal sinus development would not be complete without
mention of the ostiomeatal complex region, which represents the joint location of the
maxillary sinus ostium, anterior ethmoid sinus ostia, and frontal recess in the region of
the middle meatus. The channels into which these ostia open are bound by the ethmoidal
bulla, the uncinate process, and the middle turbinate. Anatomic enlargement or mucosal
hypertrophy of these three structures can significantly narrow these channels and obstruct
maxillary-ethmoid-frontal sinus drainage. The relatively small size of the child's nose
traditionally made intranasal sinus surgery comparatively risky because of the limited
surgical exposure, dictating an external approach. This situation has changed with the
development of instruments and telescopes of appropriate size for the application of
functional endoscopic sinus surgery directed at the ostiomeatal region in the pediatric
population.
At birth, the pinna has an adult configuration and location, although the ears appear to
rise in position as a result of the vertical growth of the lower third of the face. The pinna
reaches near adult size at 4 to 5 years of age and obtains full adult size by age 9 years.
The soft and pliable nature of the young child's ear cartilage also matures during this
same period, which influences the timing of otologic reconstructive procedures,
specifically those requiring cartilage manipulation.
The tympanic membrane is adult sized at birth but, in part because of the incomplete
ossification of the external auditory canal, lies in a nearly horizontal position, impairing
visualization on neonatal ear examinations. The final vertical orientation of the eardrum
is achieved with completion of canal ossification by approximately 2 years of age.
Eustachian tube development plays a prominent role in the predisposition of infants and
young children to middle ear infection (Fig. 70.7). At birth, the eustachian tube is about
50% of its adult length and lies in a fairly horizontal position, entering the nasopharynx at
the level of the hard palate. With growth, the eustachian tube lengthens, widens, and
angles inferiorly, achieving its final nasopharyngeal position at the level of the posterior
aspect of the inferior turbinates by the time the child is age 5 to 7 years.

FIGURE 70.7. Comparison of infant and adult middle
ear and eustachian tube development. M, malleus; I,
incus; S, stapes; ET, eustachian tube; TM, tympanic
membrane; EAC, external auditory canal.



Middle ear ossicular formation is complete at birth. Pneumatization is likewise near
complete, but the mastoid antrum enlarges over the first year of life, and generalized
mastoid pneumatization and development continue into early childhood. Most postnatal
mastoid growth occurs in a lateral and posterior direction, with a fully developed mastoid
and styloid process not appearing until the child is about age 3 (Fig. 70.8). The
extratemporal portion of the facial nerve is relatively unprotected during this period of
development, predisposing it to obstetric injury and potential iatrogenic injury during
tympanomastoid and parotid surgery. The thin mastoid cortex at this young age also
accounts for the frequent subperiosteal postauricular spread of mastoid infection.

FIGURE 70.8. Postnatal temporal bone development.
Note mastoid bony external ear canal and styloid process
growth. BEAC, bony external auditory canal; M; mastoid;
P, petrosa; S, squamosa; SF, stylomastoid foramen; SP,
styloid process; TR, tympanic ring. (From Kenna M.
Embryology and developmental anatomy of the ear. In:
Bluestone CD, Stool SE, eds. Pediatric otolaryngology,
2nd ed. Philadelphia: W.B. Saunders, 1990, with
permission.)



The petrous portion of the temporal bone, including the bony and membranous
labyrinths, is formed completely at birth. The neonate should be fully functional from
both a hearing and a vestibular standpoint. The neonate's oral cavity is small, and the
comparatively large tongue fills it entirely. The relative size of these oropharyngeal
structures contributes significantly to the infant's status as a preferential nasal breather.
The fully formed palatal structures provide the infant with velopharyngeal competence,
and the more superior cervical position of the larynx allows potential overlap of the
epiglottis and the velum, establishing a nasopharyngeal airway during suckle feeding.
The flow of milk or formula is channeled around the dorsum of the tongue and laterally
around the epiglottis, protecting the airway. With mandibular growth, the oral cavity
enlarges and the base of the tongue descends to its final hypopharyngeal position. The
infant's suckle gradually changes to a more mature swallow pattern, which remains
functionally quite complex, consisting of an extremely well-synchronized series of oral,
pharyngeal, and esophageal neuromuscular movements. The larynx serves the infant
immediately as a conduit for breathing. No other head and neck structure is initially so
essential to life. The larynx additionally protects the lower airway by means of two
mechanisms: glottic and supraglottic closure during swallowing and the cough reflex.
The phonatory function of the larynx provides the infant with a means of expressing basic
needs; this communicative function obviously increases in importance later in childhood.
The pediatric larynx has considerable anatomic differences from that of the adult. These
differences involve the specific breathing and airway protection demands of suckle
feeding in the newborn infant. The newborn neck is relatively short, and the infant larynx
is positioned high, approximating the third or fourth cervical vertebra at rest and rising to
the height of the first or second cervical vertebra with swallowing (Fig. 70.9). This high
position allows overlap of the epiglottis with the soft palate, as discussed previously.
With growth of the neck, the larynx gradually descends to its adult position opposite the
fifth cervical vertebra. The still relatively high childhood position of the larynx is
highlighted by the ease with which the epiglottis can be visualized on oropharyngeal
examination in many children.

FIGURE 70.9. Comparative neck positions of the infant
and adult larynx (glottic level).



The predisposition of the infant airway to obstruction is related to its absolute small size,
the pliability of its constituent connective tissues, and some intrinsic anatomic features.
The infantile epiglottis is furled or omega shaped and the arytenoids are relatively large,
covering a significant percentage of the posterior glottis (Fig. 70.10). This anatomic
configuration contributes to the entity of laryngomalacia. In the infant, the cricoid
cartilage is smaller in diameter than the length of the true vocal cords, making the
subglottic region the narrowest portion of the pediatric airway. The resultant funnel-
shaped internal dimension (Fig. 70.11) has important consequences for the young child in
terms of both the sequelae of inflammatory airway edema and the effects of endotracheal
intubation.

FIGURE 70.10. Endoscopic view of infant and adult
demonstrating the comparatively large arytenoids and
rounded thyroid cartilage configuration in the infant
compared with those of the adult larynx.



FIGURE 70.11. Narrowing cone-shaped internal
dimension of the infant larynx is due to the smaller
diameter of the cricoid cartilage compared with that of
the glottis. These glottic-subglottic dimensions
approximate one another in the adult larynx.



The infant larynx grows rapidly in terms of both width and length in the first 3 years of
life, which may obviate the need for airway intervention in certain congenital anomalies.
Laryngeal growth then slows until adolescence, when there is a rapid increase in all
airway dimensions. The adolescent growth spurt of the cricoid and thyroid cartilages also
changes the angulation of the true vocal cords as they insert into the anterior commissure
region. This contributes, in part, to the voice changes associated with puberty.
Of additional anatomic importance is the comparative underdevelopment of the thyroid
cartilage in the infant. The thyroid cartilage is relatively flat without a vertical midline
prominence (Fig. 70.12) and tends to be overlapped by the hyoid bone because of the
high laryngeal position. The cricoid cartilage is also small, and the cricothyroid
membrane is more of a slit than a true palpable space. The standard landmarks for
tracheotomy and cricothyroidotomy are not very demonstrable, making the emergent
performance of either of these procedures difficult in the newborn infant. Endotracheal
intubation is a far preferable choice of airway maintenance in acute emergencies in young
children.

FIGURE 70.12. Anterior view demonstration of the flat
infantile thyroid cartilage and overlap by the hyoid
cartilage above and over the cricoid cartilage below.
These cartilage elements separate with increasing age.



The neck of the infant and young child also differs from that of the adult in the
prominence of the cervical lymphoid tissue. The cervical lymph nodes increase in size
proportionally to the growth curve for the body's lymphoid tissue in general (Fig. 70.2).
The variability of cervical lymphadenopathy palpable on routine pediatric neck
examination can make the decision regarding when to perform a nodal biopsy a
diagnostic challenge. Children at risk for significant pathology include those with
supraclavicular adenopathy, worrisome clinical symptoms such as persistent fever or
weight loss, and local fixation of the node(s) to the overlying skin or underlying deep
tissues. The retropharyngeal lymph nodes make up a nodal group of additional
importance in young children. A suppurative adenitis in this region can result in abscess
formation and aerodigestive tract compromise.
CONGENITAL MALFORMATIONS
Diagnosis and management of congenital malformations of the head and neck structures
are an integral part of the practice of pediatric otolaryngology. Children with these
conditions require a thorough otolaryngologic and general pediatric assessment to ensure
that their head and neck anomaly is not a manifestation of an underlying craniofacial or
systemic syndrome. The discovery of additional syndromic manifestations could be of
prognostic importance, altering surgical or long-term care plans, and also could be of
potential use from a genetics and family planning standpoint. A comprehensive list of all
congenital malformations of the head and neck is beyond the scope of this chapter. A
brief review of several of the more common lesions highlights the diversity of a pediatric
otolaryngology practice.
Auricular Malformations
The complex origin of the middle and external ear from the first two branchial arches
lends itself to varying degrees of sporadic malformation. Minor malformations include
preauricular pits and tags. Although typically an isolated finding in normal-hearing
children, preauricular tags may be associated with ossicular malformations and secondary
conductive hearing loss. Preauricular pits can occur in the presence of renal disease and
sensorineural hearing loss in children with branchial-oto-renal syndrome.
Major auricular malformations are microtia and atresia. These may be isolated entities, or
they may occur in the setting of a generalized craniofacial disorder, such as Goldenhar
syndrome. Intervention in these children is typically dictated by the unilaterality or
bilaterality of the condition, the child's hearing status, and the feasibility or desirability of
cosmetic or hearing restoration. Such children may develop acute otitis media in the
rudimentary ear space of the microtic ear, and they have an increased risk of developing
cholesteatoma in the atretic ear canal. The normal ear in unilateral cases must be
monitored closely for otitis media with effusion and secondary hearing compromise.
Comprehensive care of children with these conditions includes parental counseling,
detailed audiologic assessment, and surgical interaction for costal cartilage harvesting in
auricular reconstruction cases.
Nares Malformations
Choanal atresia is representative of a major malformation in nares development that,
when bilateral, usually causes immediate respiratory compromise in the newborn.
Modified oral airways or endotracheal intubation provide acute airway relief until
definitive surgical management is possible. The preoperative evaluation of these patients
has been enhanced greatly by the use of high-resolution CT. Membranous or thin osseous
atresias may be approached in transnasal or transseptal fashion. The more common thick
bony atresias are treated successfully in most centers by use of the transpalatal approach.
One noteworthy exception is the group of children whose choanal atresia is one systemic
manifestation of the CHARGE association. The propensity for airway instability in these
children suggests that neonatal tracheotomy is the most appropriate initial treatment
measure, with choanal atresia repair deferred until the child is about 2 years of age. The
long-term effects of successful transpalatal repair on midfacial growth and future
velopharyngeal function remain uncertain.
Minor malformations of nares development cause varying degrees of nasal obstruction,
including both piriform aperture stenosis and choanal stenosis. Most affected neonates
can be treated conservatively with artificial airways or topical steroid drop preparations to
decrease nasal mucosal hypertrophy. Such measures often must be continued through the
infant's preferential nasal breathing period. Surgical intervention to enlarge the nasal
passages is required in a small percentage of such patients.
Midline Malformations
Encephaloceles, gliomas, and dermoids are congenital midline nasal masses whose
typical manifestations are signs and symptoms of nasal obstruction; however, they pose a
much greater risk of potential central nervous system infection, either spontaneously or
from inappropriate surgical intervention. MRI has complemented CT in the preoperative
evaluation of such lesions, and anterior craniofacial resection using the combined skills
of both the otolaryngologist and the neurosurgeon provides definitive treatment.
Malformations of the Oral Cavity
Malformations of oral cavity development frequently are associated with mandibular or
maxillary hypoplasia. Such malformations may occur as isolated entities, may be part of
a specific craniofacial disorder as in Treacher Collins syndrome, or may be one of
multiple manifestations of a systemic process as in Stickler syndrome. One of the more
common presentations is the association of retrognathia, glossoptosis, and soft palate
cleft in the so-called Robin sequence. Many children with these malformations have
airway and feeding problems. Intervention varies from special nipples and positional
feeding techniques to tracheostomy and gastrostomy in severe cases. Treatment often
needs to be continued until facial growth and neuromuscular maturation are adequate to
prevent further airway obstruction.
Cleft lip and palate is the most common malformation of the head and neck region. In
some medical centers, the pediatric otolaryngologist has the primary responsibility for the
surgical care of these patients; in other centers, the otolaryngologist functions in a
consultant role as a member of a multidisciplinary team responsible for the care of these
children. Such multidisciplinary teams likewise coordinate the care of children with
extensive craniofacial disorders at many institutions.
Airway Abnormalities
Congenital anomalies of the airway provide a particular diagnostic and therapeutic
challenge. The most common laryngeal anomaly, laryngomalacia, is in some respects one
end of the spectrum of normal neonatal supraglottic development. The clinical
presentation most often is associated with inspiratory stridor, which usually resolves
spontaneously. Infrequently, severe laryngomalacia can cause dyspnea and feeding
difficulties. Such infants historically required temporary tracheotomy. An alternative
procedure, known as an epiglottoplasty or, more appropriately, supraglottoplasty, entails
excision of the obstructive aryepiglottic folds or redundant supraglottic tissues. This
procedure has proved successful, with immediate relief of respiratory distress in these
infants.
Congenital subglottic stenosis also may represent a severe variant of normal airway
development. The time-honored standard of care for infants with this malformation was
tracheotomy pending further airway diameter growth. The anterior cricoid split
procedure, further discussed in the section on acquired airway lesions, offers a more
immediate and potentially efficacious form of therapy in these children today.
Laryngeal cleft is an uncommon and potentially devastating congenital aerodigestive tract
anomaly because of the risk of repeated aspiration. A high index of suspicion warrants a
careful endoscopic examination of the posterior commissure region in the diagnosis of
laryngeal cleft disorders. Surgical treatment of isolated laryngeal clefts includes both
anterior laryngofissure and endoscopic approaches; more extensive
laryngotracheoesophageal clefts often require a lateral cervical and thoracotomy
approach performed by a joint otolaryngology, pediatric surgery, or cardiothoracic
surgical team.
The discussion of congenital airway anomalies also must include external airway
compression by aberrant vascular structures, the most common of which is the
innominate artery. In addition to the standard workup of airway fluoroscopy and
endoscopic evaluation, a dynamic airway assessment of children with congenital airway
anomalies in the form of pulmonary function testing and flow volume loops is useful.
Such studies have expanded the clinical indications for surgical treatment of such
children to include moderate to severe exercise intolerance. MRI has replaced
arteriography as the radiologic study of choice in assessing both the anatomic degree of
airway compression and the vascular structures involved. Innominate artery compression
may be better treated by vessel realignment by means of reimplantation rather than
suspension aortopexy alone. Postoperative pulmonary function studies remain
indispensable for children in whom demonstrable residual tracheobronchomalacia exists.
Surgical options are limited; the development of tissue compatible endobronchial stents
may offer future help in children with extensive tracheomalacia.
Malformations of the Neck
Congenital malformations of the neck are a comparatively rare but interesting group of
childhood neck masses that typically present in the first two decades of life. Such
congenital lesions may present as a noninflammatory cervical mass or may go unnoticed
until secondary infection occurs. Most of these lesions arise from developmental arrest of
the fetal branchial or thyroid descent systems. The former results in an array of branchial
cysts, sinuses, and fistulae. The latter includes both thyroglossal duct cyst and ectopic
thyroid anomalies. Anatomic location on physical examination often suggests the
underlying system of origin. Definitive treatment necessitates complete excision of the
lesion, including any identifiable external tracts to the skin or internal tracts to the
aerodigestive system.
SENSORY IMPAIRMENTS
Of the sensory impairments relevant to the pediatric otolaryngologist, hearing loss is of
the greatest importance. Most hearing loss in children is mild, transient, and conductive
in nature and occurs secondary to acute otitis media or otitis media with effusion. More
severe permanent conductive hearing losses occur in the presence of congenital
anomalies of the external and middle ear. Almost all conductive hearing losses are
potentially amenable to surgical correction.
Inadequate speech and language development is typically the clue to an underlying
hearing impairment in an otherwise healthy child. The otolaryngologist and the primary
care physician must be well versed in the expected developmental milestones of receptive
and expressive language to recognize such delays (Table 70.2). In the face of a normal
otologic and audiologic assessment, alternative etiologies for inadequate language
development such as mental deficiency, dyslexia, dysarthria, or one of the disorders of
the autistic spectrum would need to be sought. Approximately 1 in 1,000 children are
born with a severe to profound sensorineural hearing loss impairment, and an equal
number of children will develop such a significant hearing loss by late adolescence. This
incidence of sensorineural deafness is increased markedly in specific populations.
Protocols have been developed in cooperation with the fields of pediatric medicine and
audiology to detect children with congenital or neonatal-acquired hearing losses in early
infancy. Earlier institution of amplification is the goal of such screening programs.

TABLE 70.2. LANGUAGE MILESTONES FOR
INFANTS AND CHILDREN FROM BIRTH
THROUGH 2 YEARS OF AGE



Early identification screening programs are feasible because of technologic refinements
in brainstem auditory-evoked response testing. Not only can frequency-specific air and
bone conduction testing be performed on infants and otherwise difficult-to-test children,
but portable screeners are now available that allow accurate identification of
handicapping hearing loss within the intensive care unit or nursery setting itself. More
recently, the presence or absence of spontaneous or evoked otoacoustic emissions has
been used in some centers as a screening device. Multichannel cochlear implant devices
have proved of great benefit for children with profound bilateral sensorineural hearing
loss who are unresponsive to conventional amplification. Strategies for assessing auditory
function and aided benefit in such children must involve behavioral testing in addition to
electroacoustic testing to identify properly those within the profoundly impaired
population who are viable candidates for implantation, particularly in the postmeningitic
bilaterally deafened population in whom the potential development of labyrinthitis
ossificans heightens concern about the need for earlier rather than later implantation.
Potential benefits from cochlear implantation include improved auditory and speech
production abilities and enhanced psychological and social integration.
Vertiginous disorders in the pediatric and adolescent age group are unusual. Both
audiologic screening and radiologic imaging of such children are extremely important to
rule out potential central nervous system lesions or temporal bone anomalies associated
with the development of a congenital perilymphatic fistula. Benign paroxysmal vertigo of
childhood and other pediatric migraine equivalents are unusual disorders that may be
variants of a spectrum of vertebrobasilar circulatory dysfunction. The vestibular testing of
children, particularly postural and vestibuloocular responses, is in its infancy. The role of
peripheral vestibular and central sensory organizational deficits in the overall motor
development of children remains undetermined. Facial nerve paralysis in children, in
contrast to that in adults, is less often idiopathic but typically represents any of a diverse
number of identifiable etiologies. A careful physical and laboratory evaluation is
necessary to rule out potential inflammatory, traumatic, neoplastic, or syndromic causes.
Electrodiagnostic testing using electroneurography can be performed accurately in
children. Transtemporal magnetic stimulation of the facial nerve has not yet been applied
widely to the pediatric population.
Vocal cord paralysis is a common cause of stridor and hoarseness in infants and children.
Unilateral pediatric paralysis most often occurs secondary to trauma or cardiac
abnormalities; bilateral paralysis is usually of neurogenic or idiopathic etiology. Any
infant or young child with bilateral cord paralysis requires a detailed neuroradiologic
workup, specifically MRI, to rule out posterior fossa abnormalities.
Bilateral and unilateral vocal cord paralyses present different problems in diagnosis and
management. Bilateral cord involvement typically results in life-threatening compromise,
whereas hoarseness and weakness of voice are the characteristic features of unilateral
paralysis. Tracheotomy is almost always necessary in the management of children with
bilaterally immobile vocal cords. Surgical techniques to permit later decannulation
include arytenoidectomy or cordotomy by endoscopic or external approach; when
performed conservatively, such procedures can improve the airway with minimal
compromise of the voice. Alternative reinnervation techniques using nerve or muscle
pedicle graft implantation into one or both posterior cricoarytenoid muscles hold promise
as a voice-preservation method. Persistent voice change resulting from unilateral
paralysis refractory to speech and language therapy also has various therapeutic options,
including gelfoam or fat injection, surgical medialization techniques, and unilateral
reinnervation. An overall conservative approach to the treatment of vocal cord paralysis
is recommended in children in light of the increased likelihood of spontaneous recovery,
especially in idiopathic and neurogenic cases.
The treatment of a child with multiple sensory impairments is best typified by Mbius
syndrome. Children who have this complex neurologic disorder have bilateral facial
paresis associated with lateral gaze paralysis. Involvement of the glossopharyngeal,
vagal, and hypoglossal nerves is also common. External, middle, and inner ear
abnormalities, including sensorineural hearing loss, may occur in addition to limb,
shoulder, and craniofacial skeletal abnormalities. Protection of eyes against drying from
exposure to air, hearing loss, airway obstruction secondary to laryngeal paralysis,
dysphagia, and secondary aspiration all are issues that may require the otolaryngologist's
intervention. Tracheotomy and feeding gastrostomy are required in most children with
multiple sensory impairments, and laryngeal diversion procedures are necessary in those
with life-threatening aspiration.
Pediatric otolaryngologists also evaluate children who demonstrate severe sialorrhea
secondary to impaired oral-motor control and swallowing. Most of these children have
severe neurologic deficits, particularly cerebral palsy. When behavioral and medical
management techniques fail, several surgical options exist. Destruction of
parasympathetic nerve fibers within the tympanic and chorda tympani nerves, rerouting
of salivary flow by submandibular or parotid duct relocation, and bilateral submandibular
gland excisions combined with parotid duct ligations are offered as definitive means of
removing the major sources of saliva production both at rest (submandibular glands) and
during food stimulation (parotid glands).
INFECTIOUS DISEASES
Otitis Media
Otitis media remains the most common childhood illness. Although there is general
agreement as to the etiology and treatment of recurrent acute otitis media, many questions
remain concerning the clinical sequelae and management of otitis media with effusion.
The suspected long-term ill effects of bilateral and even unilateral middle ear effusion on
eventual speech-language development and cognitive function are just beginning to be
elucidated. Controversy remains concerning the role of steroids and even antibiotic
therapy in the treatment of nonacute middle ear disease, and trials regarding potentially
efficacious drugs, such as mucolytic agents and nonsteroidal antiinflammatory agents,
remain to be undertaken. Prophylactic measures such as the pneumococcal vaccine are
currently being tested. The relative roles of tympanostomy tube placement and
adenoidectomy will be further clarified by outcome studies.
Rhinosinusitis
The diagnosis and treatment of rhinosinusitis in the pediatric population have undergone
revolutionary changes in recent years. Increasing evidence supports the middle meatal-
anterior ethmoid region as the primary site of involvement of most inflammatory sinus
disease. This so-called ostiomeatal complex serves as the area in which mucociliary
clearance from the frontal, ethmoid, and maxillary sinuses may become obstructed.
Systematic nasal endoscopy and high-resolution coronal and axial CT have markedly
increased the ability to diagnose disease in this region. Technologic improvements led to
the use of functional endoscopic sinus surgery in children in whom maximum medical
management of rhinosinusitis has failed. The role of such surgery needs to be elucidated
more fully in selected populations of children, such as those with primary
immunodeficiency disorders, immotile cilia syndromes, and severe atopic disorders,
including allergic fungal sinusitis. Furthermore, the long-term effects of functional
endoscopic sinus surgery on human facial growth have yet to be completely determined.
Cystic Fibrosis
Children and young adults with cystic fibrosis are another special group of patients.
Chronic pansinusitis is an almost universal problem in this population, with a variable
incidence of obstructive nasal polyposis. Medical therapy offers limited benefit in the
treatment of cystic fibrosis polyps. Wide antrotomy of the maxillary, frontal, and
sphenoid sinuses combined with ethmoidectomy using an endoscopic technique has
proved efficacious. Initial treatment success must be judged relative to the likelihood of
postoperative polyp recurrence.
Haemophilus influenzae and Streptococcus pneumoniae Infection
Among the newest infectious disease breakthroughs is the development of the
Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae conjugated
vaccines applicable for administration to infants and young children. The availability and
widespread use of the Hib vaccine has had several beneficial consequences, including a
decreased incidence of Hib meningitis and its secondary hearing loss. Hib is also the
etiologic agent of acute supraglottitis, and the marked reduction in the frequency of this
life-threatening laryngeal infection has been an extremely gratifying result of this
vaccine's general use. The heptavalent pneumococcal conjugate vaccine has only recently
been approved for general pediatric use. Pilot studies indicate that infant immunization
with this vaccine will decrease the incidence of invasive pneumococcal infections like
meningitis by over 90% and noninvasive infections like acute otitis media by
approximately 10%.
Neoplastic disorders (see Chapter 87) and trauma (see Chapter 92) are discussed
elsewhere in this volume.
ADENOTONSILLAR SURGERY
The pediatric otolaryngologist shares with his or her general otolaryngology colleagues
many of the common ear, nose, and throat procedures performed on children, particularly
adenoidectomy, tonsillectomy, and the combination thereof. As a subspecialty field,
pediatric otolaryngology has attempted to better define the clinical indications for these
common operations and to confront the medical-legal issues raised by third-party payor
mandates that such procedures should be performed on an outpatient rather than an
inpatient basis.
Severe recurrent pharyngitis has been and remains the predominant indication for
adenotonsillectomy. This procedure has been effective in treating severely affected
children with repeated throat infections. Obstructive sleep apnea accounts for a
continually increasing percentage of adenotonsillectomy cases. The etiology of
obstructive sleep apnea is multifactorial, with craniofacial airway dimensions, overall
muscle tone, and the rapid increase in pharyngeal and palatine lymphoid tissue size over
the first several years of life playing major contributory roles. The efficacy of
tonsillectomy, with or without adenoidectomy, in the relief of obstructive sleep apnea is
well established by studies incorporating preoperative and postoperative
polysomnography monitoring. The establishment of sleep laboratories run by pediatric
pulmonary and neurology colleagues has aided greatly the understanding of the
pathophysiology of this disorder and enhanced the perioperative care of severely afflicted
persons. Children with craniofacial disorders, such as Down syndrome and
achondroplasia, or those with severe hypotonia as a result of cerebral palsy and other
neuromuscular disorders may have obstruction that cannot be reversed by
adenotonsillectomy alone. Pharyngoplasty and even tracheotomy may be required.
The increasing pressure on otolaryngologists to perform adenotonsillectomy as an
ambulatory procedure has focused attention on surgical techniques, methods of
hemostasis, and perioperative management. Conventional dissection and snare techniques
have been compared increasingly with electrocautery dissection and laser excision
relative to postoperative pain and hemorrhage. The perioperative use of antibiotics or
steroids, the local and systemic administration of narcotics and other analgesics, and the
alteration of anesthesia and hydration practices in an attempt to improve postoperative
pain control and reduce the risk of postoperative sedation all have been subjects of
investigation.
SPECIAL ISSUES
Children are not cared for in isolation. All pediatric otolaryngology encounters are
modified to some degree by the close identification of the parent(s) and other family
members with the child.
The family is the major source of the clinical history of the young child and complements
the history obtained from older children. A family member is often needed to hold the
infant or toddler during the head and neck examination. The vigor with which this is
pursued must balance the need to examine the child adequately with the need to maintain
the confidence and trust of the family.
Treatment recommendations must consider family dynamics and the role of secondary
caretakers in day-care or school settings. This may influence medication dosage
schedules or modes of administration. Deferring to the child's preferences for one
flavored medication over another or for an available liquid or chewable form may greatly
improve compliance.
The ill child who requires frequent office visits, hospitalization, or surgery places
numerous stresses on the family unit. Extended families with grandparents or other
relatives within the home are rare today. Most are nuclear families with two working
parents in which economic and social sacrifices are necessary so that at least one parent is
present with the child throughout the course of treatment. This poses an even greater
burden on single-parent families. In cases of prolonged hospitalization, the intervention
of social services is often of great help. Strong consideration also should be given, when
appropriate, to home nursing care; a need for prolonged administration of intravenous
antibiotics is one such example.
Acquiring surgical consent for children from parents or other primary caretakers typically
requires a great amount of time and counseling. Special problems in this regard include
legally separated families, in which case instructions must be provided individually to
both parents, and foster care families, in which case the social service or judicial system
is the child's guardian.
The administration of anesthesia, especially in the child undergoing a first-time
procedure, is often of equal or greater concern to the family than the operation itself.
These fears can be decreased significantly by the use of preoperative anesthesia
consultations and educational programs coordinated by a hospital-based child life
therapist. Such programs require the family to attend a preoperative hospital session
during which the parent(s) and child are prepared for what will occur on the day of
surgery; one parent then is allowed to enter the operating room and remain at the child's
side during the induction of anesthesia in age-appropriate elective cases.
Preoperative guidelines also have changed in recent years relative to the need for
prolonged fasting. Increased knowledge concerning fluid and electrolyte maintenance in
infants and young children has suggested that only 4 to 6 hours of absolute fasting is
necessary and that clear fluids offered several hours before planned induction do not
increase the child's risk of pulmonary aspiration. This change in practice both avoids the
anesthetic risks of induction in a hypovolemic child and creates a much more humane
preoperative period for the child and family.
The family must be informed of the immediate care needs of the postoperative child,
especially in outpatient surgery cases in which the presence of two caretakers may be
necessary for the trip home afterward. The anesthesia team plays a special role in the
ambulatory surgery setting. The use of sedative, antiemetic, and anesthetic agents can be
varied to result in a more alert, less systemically ill, postoperative child.
CONCLUSION
The subspecialty of pediatric otolaryngology has grown from that of a few individual
otolaryngologists in the 1960s to the degree that most academic centers in this country
now have one or more pediatric otolaryngologists on their full-time staffs. An increasing
percentage of private-practice hospital-affiliated otolaryngologists also devote their
careers principally or solely to pediatric otolaryngology. More than a dozen fellowships
currently exist, and attempts are under way to formalize pediatric otolaryngology
fellowship training from a didactic instruction, clinical responsibility, and research
experience standpoint. These fellowships will continue to produce otolaryngologists
committed to the ear, nose, and throat disorders of children. Their work and
accomplishments will continue to benefit pediatric patients directly and will indirectly
strengthen the comprehensive management of the otolaryngologic manifestations of
disease for our specialty overall.

HIGHLIGHTS
The subspecialty of pediatric otolaryngology focuses on a
specific age group rather than a single organ system or category
of disease. It is the study of the disorders of the ears, nose, and
throat relative to the growth and development of the head and
neck structures.
Marked anatomic, physiologic, and behavioral changes occur
along the continuum from infancy through childhood and
adolescence into adulthood. The clinical presentation of any
otolaryngologic disease process is greatly influenced by the age
and maturation of the afflicted person.
Children with congenital malformations of the head and neck
require a thorough general pediatric assessment to ensure that
their otolaryngologic anomaly is not just one manifestation of a
systemic syndrome. The discovery of additional syndromic
findings could change both acute and chronic treatment plans
significantly.
Refinements in endoscopic instrumentation have influenced
multiple aspects of pediatric otolaryngologic care, particularly
true in the diagnosis and management of congenital and
acquired airway lesions and the surgical treatment of infectious
paranasal sinus disease.
Of the sensory impairments of relevance to pediatric
otolaryngology, none is of greater significance than hearing
loss. Otolaryngologists who care for children must be
knowledgeable about the expected developmental milestones of
receptive and expressive language from both a diagnostic and
rehabilitative standpoint.
High-risk screening programs coupled with auditory brainstem
response testing are designed to allow earlier identification of
hearing-impaired infants and children. The multichannel
cochlear implant device holds great promise for those children
with profound bilateral sensorineural hearing loss who are
unresponsive to conventional amplification.
Refinements in angiographic embolization, microvascular
techniques, and craniofacial approaches have broadened the
definition of resectability without deformity in many children
with benign and malignant head and neck neoplasms.
The maturational changes of the facial skeleton, particularly
those associated with paranasal sinus and dentition
development, significantly alter the clinical presentation of
maxillofacial trauma in the pediatric population.
Acquired airway lesions secondary to endotracheal intubation
are one of the most common otolaryngologic sequelae of
intensive care unit survival. The concept of expansion of the
stenotic airway in preference to stenosis resection in children is
generally well accepted.
Children are not cared for in isolation. All pediatric
otolaryngology encounters are influenced to some degree by the
close identification and vested interest of the parent(s) and other
family members with the ill child.
CHAPTER REFERENCES
1. McMurray JS, Holinger LD. Otolaryngic manifestations in children presenting with apparent life-
threatening events. Otolaryngol Head Neck Surg 1997;116[6 Pt 1]:575579.
2. Pizzuto MP, Volk MS, Kingston LM. Common topics in pediatric otolaryngology. Pediatr Clin
North Am 1998;45:973991.
3. Furman RH, Backer CL, Dunham ME, et al. The use of balloon-expandable metallic stents in the
treatment of pediatric tracheomalacia and bronchomalacia. Arch Otolaryngol Head Neck Surg
1999;125:203207.
4. Armstrong LR, Derkay CS, Reeves WC. Initial results from the national registry for juvenile-onset
recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 1999;125:743748.
5. Van Den Abbeele T, Triglia JM, Lescanne E, et al. Surgical removal of subglottic hemangiomas in
children. Laryngoscope 1999;109:12811286.
6. Brodsky L, Brookhauser P, Chait D, et al. Office-based insertion of pressure equalization tubes:
the role of laser-assisted tympanic membrane fenestration. Laryngoscope 1999;109:20092014.
7. Benjamin BNP. Diagnostic laryngology: adults and children. Sydney, Australia: W.B. Saunders,
1990.
8. Bluestone CD, Stool SE, eds. Pediatric otolaryngology, 3rd ed. Philadelphia: W.B. Saunders,
1996.
9. Healy GB, ed. Common problems in pediatric otolaryngology. Chicago: Mosby Year Book, 1990.
10. Myer CM III, Cotton RT. A practical approach to pediatric otolaryngology. Chicago: Mosby
Year Book, 1988.
11. Werner JA, Lippert BM, Hoffmann P, et al. Nd:YAG laser therapy of voluminous hemangiomas
and vascular malformations. Adv Otorhinolaryngol 1995;49:75.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

71 AIRWAY IMAGING IN CHILDREN
Head & Neck SurgeryOtolaryngology
71




AIRWAY IMAGING IN CHILDREN
SUSAN D. JOHN
LEONARD E. SWISCHUK

S.D. John: Department of Radiology, University of TexasHouston Medical School, Health Science
Center, Houston, Texas.
L.E. Swischuk: Department of Pediatric Radiology, University of Texas Medical Branch Children's
Hospital, Galveston, Texas.


Upper Airway Obstruction
Supraglottic Obstruction
Glottic Obstruction
Subglottic Obstruction
Retropharyngeal Masses and Thickening
Nasal and Nasopharyngeal Obstruction
Chapter References
Decisions about the type of imaging to request for evaluating pediatric airway disorders
have been complicated in recent years by an ever-growing number of available
modalities. Sectional imaging (e.g., computed tomography [CT], magnetic resonance
imaging [MRI], ultrasound) has provided improved anatomic detail and soft-tissue
characterization. However, such procedures are somewhat costly and may require
sedation in young children. Plain radiography and fluoroscopy continue to be the
mainstays of airway imaging in children (1). Air serves as an excellent contrast material,
and with proper attention to technique and positioning, the important anatomic landmarks
in the upper airway and trachea can be easily distinguished on plain radiographs.
Fluoroscopy provides the additional advantage of real-time imaging of the dynamics of
the airway during respiration. Ultrasound, CT, and MRI all have selected uses for airway
imaging, predominantly when evaluating soft-tissue structures that may be secondarily
affecting the airway. This chapter discusses imaging approaches to some of the common
airway disorders in children.
UPPER AIRWAY OBSTRUCTION
The etiology of an acute episode of stridor in an infant or child can often be determined
clinically without the use of imaging. However, in those cases in which clinical
uncertainty exists, plain radiographs are frequently sufficient to define the anatomy and
localize the site of obstruction. Good quality radiographs are essential, and important
technical factors include precise anteroposterior (AP) and lateral positioning, adequate
neck extension, and full degrees of inspiration or expiration. High-kilovoltage techniques
with filtration and magnification are preferred by some radiologists, but we do not find
such techniques necessary in most cases. Airway fluoroscopy permits direct visualization
of the dynamics of the upper airway and trachea during inspiration and expiration.
Fluoroscopy is particularly useful in infants and young children who have rapid and
shallow respiration and cannot cooperate with commands.
A lateral view of the upper airway taken in full inspiration shows a well-distended
hypopharynx, an almost vertical epiglottis, and thin aryepiglottic folds that extend
obliquely to the triangular shadow of the arytenoid cartilage (Fig. 71.1A). The false and
true vocal cords can be visualized as linear bands of soft-tissue density above and below
the laryngeal ventricle. The normal subglottic trachea should be well distended and even
in caliber. With expiration, the supraglottic structures collapse, but the subglottic trachea
remains widely patent (Fig. 71.1B).

FIGURE 71.1. Normal airway. A: Lateral view on
inspiration demonstrates the normal epiglottis (E),
aryepiglottic folds (AE), arytenoid cartilage (A), laryngeal
ventricle (V), true vocal cords (VC), and palatine tonsils
(T). B: On this normal expiratory lateral view, the
supraglottic structures collapse. Note the abrupt cutoff of
the tracheal air column at the glottis (G) and the normal
anterior buckling of the upper trachea (arrow). C:
Normal inspiratory anteroposterior view shows minimal symmetric narrowing at the level
of the glottis (arrows). D: Normal expiratory view (with Valsalva maneuver)
demonstrates closure of the glottis in the midline and a normal-diameter subglottic
trachea. Note the acute angle at the inferior margin of the vocal cords (arrows).



On frontal radiographs with inspiration, minimal narrowing is seen at the glottis due to
the abducted vocal cords (Fig. 71.1C). With expiration (which is often accompanied by a
Valsalva maneuver), the adducted vocal cords meet at the midline, and their inferior
margins make an acute almost 90-degree angle with the walls of the subglottic trachea
(Fig. 71.1D). The upper trachea characteristically buckles anteriorly and to the right on
expiration in infants and young children, possibly due to a plunger effect with the upward
movement of the normal thymus gland into the thoracic inlet. When upper airway
obstruction develops, these normal airway configurations become altered, and the pattern
of alteration helps to localize the site of obstruction.
Supraglottic Obstruction
The most common causes of obstruction at the supraglottic level are inflammation
(epiglottitis), laryngomalacia, masses, and foreign bodies. Masses and foreign bodies are
often clearly visible as radiopaque structures within the air-filled hypopharynx (Fig.
71.2).

FIGURE 71.2. Hypopharyngeal foreign body. Note the
oval-shaped opacity (arrows) adjacent to the normal
palatine tonsils (T). A grass burr was found in the
hypopharynx. (Courtesy of C. Keith Hayden, Jr., MD,
Fort Worth, Texas.)



The diagnosis of acute epiglottitis is usually easily accomplished with plain radiographs.
Because of the risks of rapid progression in this condition leading to complete airway
obstruction, the radiograph should be obtained promptly with minimal manipulation of
the neck. Patients with suspected epiglottitis should never be sent unattended to the
radiology department. The classic radiographic findings include variable degrees of
thickening of both the epiglottis and the aryepiglottic folds (Fig. 71.3). In most cases, the
vocal cords and upper trachea are normal, although occasionally inflammation can extend
into the glottic and subglottic region, causing a steeple or funnel configuration on frontal
view. In some patients, prominence of the lateral folds of the epiglottis cause it to appear
bulky on lateral view (the omega epiglottis). However, in such cases, the aryepiglottic
folds will remain thin, and the posterior wall of the epiglottis remains clearly visible (Fig.
71.4). Care should be taken not to mistake the prominent triangular configuration of the
arytenoid cartilage at the base of the aryepiglottic folds for fold thickening (2). Other rare
causes of epiglottic enlargement include angioneurotic edema, candidal infection
(especially in immunocompromised patients), burns due to corrosive ingestion, laryngeal
sarcoidosis, neoplasms (e.g. hemangioma), lymphatic malformation, allergic reactions,
and aryepiglottic fold cysts.

FIGURE 71.3. In this patient, the epiglottis is difficult to
delineate, but note the thickened aryepiglottic folds
(arrow).



FIGURE 71.4. Normal epiglottis. The epiglottic shadow
appears bulky in this patient because of prominence of
the lateral folds, but the aryepiglottic folds are normal in
thickness (arrow). Prominence at the base of the folds
represents the normal triangular configuration of the
arytenoid cartilage (A).



The most common cause of inspiratory stridor and supraglottic obstruction in neonates
and young infants is laryngomalacia. Stridor in such infants typically develops within the
first few weeks of life because of immaturity of the laryngeal cartilages and muscles,
which allows the larynx and supralaryngeal structures to collapse during inspiration.
Laryngomalacia is one of the few conditions in which stridor improves with agitation or
activity of the infant and worsens at rest. The condition is self-limited and usually
resolves by age 1 year.
Typical radiographic findings of laryngomalacia consist of downward and posterior
bending of the epiglottis and anteroinferior buckling of the aryepiglottic folds during
inspiration. Eventually these structures collapse and obliterate the supraglottic and glottic
airway. This phenomenon can occasionally be captured on plain radiographs, but the
episodes of obstruction are very transient and are usually best seen with fluoroscopy. The
condition is also readily detected with endoscopy.
Glottic Obstruction
Obstruction at the level of the glottis can result from a variety of causes of thickening
and/or fixation of the vocal cords. The radiographic clues to the presence of glottic
obstruction result from the changes in the dynamics of the air flow through the glottis and
the subglottic trachea. When the glottic airway becomes narrowed for any reason, air
passes through the glottis with increased velocity, creating increased pressure in the
forward vector and decreased pressure in the lateral vector. The decline in lateral or
centrifugal pressure causes the subglottic portion of the trachea to collapse and decrease
in diameter (3) (Fig. 71.5A). In addition, the hypopharynx overdistends, and the
aryepiglottic folds are stretched. These findings are dependent on the degree of
inspiration, and if the inspiratory effort is less than maximum, the radiographic findings
will be minimal. The fixed vocal cords, on lateral view, tend to appear less distinct than
usual with such conditions.

FIGURE 71.5. Glottic obstruction in a child with croup.
A: On lateral inspiratory view, note the distention of the
hypopharynx and a diffuse narrowing of the subglottic
trachea (arrows). B: An expiratory lateral view on the
same patient shows collapse of the hypopharynx and re-
expansion of the subglottic trachea to a near-normal
caliber. C: On anteroposterior view, the glottic airway is
narrowed, and the inferior margin of the vocal cords has
lost its acute angle and appears tapered (arrows). This creates a steeple or funnel-shaped
configuration.



The most common cause of glottic obstruction in children is croup
(laryngotracheobronchitis). This condition most commonly is viral in origin and is
usually mild and self-limited. Clinically, croup is characterized by predominantly
inspiratory stridor, often accompanied by fever, hoarseness, and a characteristic
barking cough. A child who presents with typical signs and symptoms usually requires
no imaging, but lateral neck radiographs are often obtained and can quickly confirm the
diagnosis. The typical findings of glottic obstruction are usually demonstrated, including
hyperdistention of the hypopharynx, indistinctness of the vocal cords, and paradoxical
narrowing of the subglottic trachea on inspiration, with return to normal or near-normal
caliber on expiration (Fig. 71.5B). On AP view, the edematous spastic vocal cords cause
a steeple or funnel-shaped configuration at the glottis (Fig. 71.5C). Membranous croup
(bacterial tracheitis) is a more serious form of laryngotracheal inflammation, most often
caused by Staphylococcus aureus. Symptoms are similar to those of viral croup but tend
to be more rapidly progressive and severe. Radiologically, membranous croup can be
suggested when irregularity of the walls of the subglottic trachea due to mucosal edema
and membrane formation is identified. Occasionally, the membranes become detached
from the wall and can be seen as transverse or oblique linear soft-tissue structures in the
upper trachea (Fig. 71.6). Croup also can be seen on an allergic basis.

FIGURE 71.6. Membranous croup (bacterial tracheitis).
Note the oblique soft-tissue band extending across the
subglottic tracheal lumen (arrows).



Vocal cord paralysis is a relatively common cause of glottic obstruction in the neonate
and young infant, most often due to congenital abnormalities of the central nervous
system. In older infants and children, vocal cord paralysis is more often acquired and of
acute onset, frequently due to trauma to the cords or the recurrent laryngeal nerve,
postviral neuropathy, or central nervous system tumors. Airway obstruction is most
commonly caused by bilateral abductor paralysis, and the lateral neck radiographic
findings are identical to those seen with croup. However, the condition can be
distinguished from croup on AP view because the vocal cords will remain apposed and
show little or no movement with inspiration and expiration. Unilateral vocal cord
paralysis causes asymmetry of the glottis on AP view, and again, the abnormal cord will
be that which lacks movement on inspiration and expiration. Real-time demonstration of
abnormal vocal cord motion is most often accomplished with fluoroscopy. More recently,
ultrasound has been used to examine the larynx and seems to be a promising method for
the diagnosis of functional disorders and masses of the larynx (4).
Congenital laryngeal web is an uncommon cause of stridor and glottic obstruction. The
webs are usually located immediately below the vocal cords and cause some degree of
fixation of the cords. Therefore, the radiographic findings on lateral view are the same as
those seen with croup and vocal cord paralysis. On frontal view, fixation of the cords
similar to that seen with vocal cord paralysis occurs. Because the web itself cannot be
visualized radiographically and the secondary findings are nonspecific, the diagnosis
usually is established with endoscopy.
Laryngeal masses are rare in children, except for the laryngeal papilloma. This benign
neoplasm most often involves the true vocal cord, but supraglottic and tracheobronchial
extension is common. Laryngeal papillomas are best seen radiographically on the lateral
view, where they produce nodular thickening of the vocal cords (Fig. 71.7).

FIGURE 71.7. Laryngeal papilloma. Note the well-
defined soft-tissue nodule at the level of the true vocal
cord (arrows).



Subglottic Obstruction
Obstruction in the subglottic portion of the trachea is most commonly the result of
subglottic stenosis. Such stenosis can occur congenitally but is more often acquired due
to prolonged endotracheal intubation. Congenital stenosis usually consists of a short
segment of circumferential narrowing immediately below the vocal cords. The narrowing
in acquired subglottic stenosis may be circumferential but is often asymmetric, and the
length of trachea involved is variable. In either type of stenosis, narrowing persists during
both inspiration and expiration (Fig. 71.8). Plain radiographs and fluoroscopy are usually
sufficient to establish the diagnosis of subglottic stenosis; however, CT or MRI is
sometimes useful for more precise assessment of the exact site and length of the stenosis
(5,6) (Fig. 71.9A and Fig. 71.9B). Three-dimensional CT produces elegant graphic
displays of airway narrowing (7) (Fig. 71.9C).

FIGURE 71.8. Subglottic stenosis. Note the concentric
focal narrowing of the trachea at the level of C-7
(arrows). This narrowing remained fixed on inspiration
and expiration.



FIGURE 71.9. Tracheal and bronchial stenosis. A:
Sagittal T1-weighted magnetic resonance image better
demonstrates the multiple asymmetric areas of stenosis
(arrows). B: Three-dimensional computed tomography
demonstrates focal narrowing of the left bronchus
(arrow), due to congenital stenosis.



Tracheomalacia is an uncommon condition characterized by hypercollapsibility of the
trachea on expiration due to weakness of the supporting cartilage and muscles.
Tracheomalacia is most often focal and occurs as a complication of chronic intubation or
any congenital condition that produces pressure on the trachea prenatally (e.g., vascular
rings, dilated pouch of esophageal atresia). In such cases, some degree of tracheal
narrowing is usually seen on both inspiration and expiration, but the expiratory narrowing
predominates (Fig. 71.10). Rarely, the entire trachea may be involved, usually in
conjunction with conditions that are associated with abnormal cartilage (e.g.,
polychondritis). The trachea in such patients becomes markedly and diffusely narrowed
on expiration. Be aware, however, that occasionally a normal infant will show dramatic
diffuse expiratory tracheal narrowing. Plain radiographs and fluoroscopy are sufficient to
diagnose tracheomalacia in most cases, but the predisposing condition is usually better
characterized by a barium esophagram, CT, or MRI (6,8) (Fig. 71.11).

FIGURE 71.10. Tracheomalacia in an infant with a
history of esophageal atresia. A: Inspiratory radiograph
demonstrates a patent trachea with minimal narrowing
near the carina (arrows). B: The same patient on
expiration shows complete collapse of the distal trachea.



FIGURE 71.11. Tracheomalacia secondary to a vascular
ring. A: Posteroanterior chest radiograph shows focal
narrowing of the trachea (arrow) and a round right
paratracheal mass (arrowheads) that represents a right
aortic arch. B: Bilateral indentations on the barium-filled
esophagus (arrows) represent impressions by the
encircling double aortic arches. C: Axial T1-weighted
magnetic resonance image reveals flow void in the aortic
arches (arrows) as they encircle the narrowed trachea (T).



The most common mass involving the subglottic trachea is the benign hemangioma.
These vascular neoplasms are usually present from birth, but because of their tendency to
enlarge, in some cases the symptoms will not be noted until later in infancy.
Hemangiomas typically occur on the lateral or posterior walls of the subglottic trachea
and thus produce a characteristic eccentric narrowing (Fig. 71.12). Occasionally,
hemangiomas arising outside of the trachea can encircle the subglottic trachea and cause
a more circumferential pattern of narrowing (9). Other less common causes of eccentric
subglottic tracheal narrowing include granulomas due to previous endotracheal
intubation, ectopic thyroid or thymus tissue, subglottic mucoceles, postinflammatory
histiocytoma, and tracheal cysts.

FIGURE 71.12. Subglottic hemangioma. A: The lateral
view shows minimal focal narrowing along the posterior
wall of the subglottic trachea (arrow). B: On
anteroposterior view, asymmetric narrowing is evident
due to a typically eccentric subglottic hemangioma that
lies predominantly along the left lateral tracheal wall
(arrow).



Foreign bodies must always be considered as a potential cause of unexplained stridor in a
young child. Small foreign bodies may be aspirated into the glottis or upper trachea, but it
is rather rare for them to become lodged at this level. On the other hand, esophageal
foreign bodies are quite common and may not be suspected if the caretaker has not
actually witnessed the ingestion. Ingested items, such as coins, frequently become lodged
at the level of the cricopharyngeal muscle or the aortic arch. Such retained foreign bodies,
especially those that are chronically imbedded, produce periesophageal edema that can
lead to tracheal compression and stridor (Fig. 71.13). Coins are easily visible
radiographically, but nonradiopaque foreign bodies often require barium examination for
diagnosis.

FIGURE 71.13. Esophageal foreign body. Note the
quarter that is lodged in a typical location at the level of
the aortic arch. Increased space between the esophagus
and trachea and adjacent focal tracheal narrowing (arrow)
indicate edema.



RETROPHARYNGEAL MASSES AND THICKENING
Conditions that produce marked thickening of the retropharyngeal soft tissues
occasionally encroach sufficiently on the upper airway to produce airway obstruction.
Inflammatory lymphadenopathy and retropharyngeal abscess are the most common
causes of soft-tissue enlargement in this region in children. Bacterial infections in the
paranasal sinuses, nasal cavity, throat, and middle ear drain into the retropharyngeal
lymph nodes in young children, resulting in lymph node enlargement and prevertebral
cellulitis. Retropharyngeal abscesses most often develop when such lymphadenopathy
becomes suppurative and necrotic. In most cases, retropharyngeal infection can be
identified with a lateral neck radiograph. The enlarged lymph nodes and edematous
retropharyngeal tissue produce soft-tissue thickening that causes convex anterior
displacement of the posterior pharyngeal airway, with loss of the normal step-off at the
origin of the esophagus (Fig. 71.14). Be wary of radiographs taken with less than
complete degrees of inspiration (10), which can erroneously suggest retropharyngeal
thickening and even abnormal gas collections (Fig. 71.15). Muscle spasm secondary to
the retropharyngeal inflammation often causes straightening, or hyperflexion, of the
cervical spine.

FIGURE 71.14. Retropharyngeal abscess. A: Lateral
radiograph shows marked thickening of the prevertebral
soft tissues, with loss of the normal step-off at the origin
of the esophagus (arrows). B: Transverse ultrasound
image of the neck reveals an irregular complex fluid
collection within the retropharyngeal soft tissues
(arrows). P, pharynx; M, muscle; A, carotid; V, jugular
vein. C: Multiple nonsuppurative nodes were also seen
more superficially in the neck (arrows).



FIGURE 71.15. Pseudoabscess of the retropharynx. A:
Note the apparent thickening of the retropharyngeal soft
tissues, with a small central collection of gas that
suggests the presence of an abscess (arrow). However,
also note the typical anterior buckling of the subglottic
trachea, indicating that this film was taken on expiration.
B: A repeat film obtained with a better degree of
inspiration shows normal retropharyngeal soft tissues and
subglottic inspiratory tracheal narrowing consistent with croup.



Frequently, the radiographic appearance of the thickened retropharyngeal tissues is
nonspecific and does not permit distinction of simple lymphadenopathy from an abscess.
In a few cases, gas will be noted within the thickened retropharyngeal tissues, which is a
fairly reliable indication of abscess formation. More commonly, some other type of
imaging will be required to make the distinction, and often CT is chosen. An abscess
appears as a focal area of low attenuation within the retropharyngeal soft tissues, often
with a rim of contrast enhancement (Fig. 71.16). The attenuation value of the abscess
may vary somewhat depending on the amount of debris and/or air within the abscess
cavity. Retropharyngeal lymphadenopathy also may demonstrate moderately low
attenuation values even in the absence of abscess formation, but simple adenitis or edema
lacks an enhancing rim. Ultrasound can be helpful to verify the presence or absence of a
drainable fluid collection (11,12) (Fig. 71.14). Retropharyngeal lymphadenopathy and
abscesses are also easily identified with MRI. Both produce focal areas of low signal
intensity on T1-weighted images that increase in signal intensity on the T2-weighted
images. MRI tends to be used less commonly because in young children it is more
difficult to accomplish without heavy sedation.

FIGURE 71.16. Retropharyngeal abscess. Straightening
of the cervical spine is typical, due to muscle spasm. A:
Contrast-enhanced computed tomography reveals an
irregular area of low attenuation with minimal rim
enhancement (arrows), consistent with an abscess. B: T2-
weighted axial magnetic resonance image of another
patient shows a high-intensity fluid collection (abscess) in
the right retropharyngeal space (arrows).



Noninflammatory lymphadenopathy and retropharyngeal extension of tumors of the neck
are moderately common causes of retropharyngeal soft-tissue thickening in children.
Ultrasound is the procedure of choice for screening neck masses in children (13),
particularly those that are clinically soft or fluctuant, such as lymphatic malformation,
hemangioma, lipoma, and a variety of cysts. These masses are among the most common
neck masses in infants and children, and each has a fairly characteristic sonographic
appearance. A lymphatic malformation shows a multiloculated cystic appearance,
sometimes with echogenic material within the loculations due to internal hemorrhage
(Fig. 71.17A). Hemangiomas are usually predominantly solid, often with scattered
anechoic or hyperechoic areas that represent sinusoids (Fig. 71.17B). Color Doppler
imaging is very helpful for identifying the abundant blood flow within some of these
vascular lesions (Fig. 71.17C). Lipomas are homogeneously echogenic, and cysts are
completely anechoic, with well-defined thin-walled rims (Fig. 71.17D).

FIGURE 71.17. Ultrasound of neck masses. A:
Lymphatic malformation is a predominantly cystic mass
(arrows) with multiple septations. B: A hemangioma that
is heterogeneous, solid, and predominantly echogenic,
with small anechoic areas that represent vessels or
sinusoids (arrows). C: Color Doppler image (seen here in
black and white) of this hemangioma reveals the presence
of significant blood flow within the lesion. D: Cysts, such
as this branchial cleft cyst, are characteristically anechoic with thin walls (arrows). SCM,
sternocleidomastoid muscle.



Firm neck masses are most often solid lesions that have a nonspecific ultrasound
appearance, except for lymphadenopathy. Enlarged lymph nodes can be readily identified
as multiple hypoechoic oval nodules, which can sometimes become confluent, irregular,
hypoechoic masses. However, no reliable imaging characteristics permit the distinction
between inflammatory and neoplastic lymphadenopathy. Neck masses that are large or
are suspected of significant airway compromise or invasion of the calvarium, spinal
canal, or chest are better defined with CT or MRI (14) (Fig. 71.18).

FIGURE 71.18. Neck massneurofibromas. T2-
weighted axial magnetic resonance image shows
extensive high-intensity neurofibromas in the right neck,
extending into the retropharynx and compromising the
airway (small arrows) and also extending into the spinal
canal (large arrow).



NASAL AND NASOPHARYNGEAL OBSTRUCTION
In the neonate and young infant, the most common cause of nasal obstruction is
congenital choanal atresia. This developmental anomaly can be bilateral or unilateral, and
the initial diagnosis can be made clinically by the inability to pass a catheter through the
nose into the pharynx. However, imaging can provide valuable information about the
composition and severity of the obstruction, which can range from stenosis with
incomplete obstruction to complete obstruction with either membranous or bony atresia
(15). Radiographs with contrast injected into the nasal cavity can demonstrate the level of
obstruction, but this examination has been essentially replaced by the use of CT. Thin-
section (1.5 mm thick) axial CT images with bone and soft-tissue windows can give
detailed information about the imperforate membranes and bony overgrowth that are
characteristic of this anomaly (Fig. 71.19). Images can also be reconstructed in the
sagittal plane. The nasal passage should be suctioned before performing the CT to
eliminate retained secretions that can obscure the true thickness of the soft-tissue
component of the anomaly.

FIGURE 71.19. Choanal atresia. Note the thickened
vomer (arrowheads) and bony stenosis of the choanal
apertures with persistent soft-tissue membranes causing
obstruction (arrows). The thickness of the membrane is
difficult to determine because secretions were not
suctioned from the nose before imaging.



The choanal orifices normally measure greater than 0.37 cm in children under 2 years of
age, and the vomer does not exceed 0.34 cm in children less than 8 years of age (16,17).
Ninety percent of children with choanal atresia have a bony component. Typically in
children with bony choanal atresia, CT demonstrates medial bowing and thickening of
the lateral walls of the nasal cavity, which are fused with the enlarged vomer. Some
degree of narrowing of the bony nasal passage and vomer thickening is usually also
present with membranous atresia.
Obstruction due to a nasal mass is uncommon in children, but a wide variety of masses
can occur in this region. Many masses can be identified radiographically as increased
soft-tissue opacity within the nasal cavity, but the findings are very nonspecific. CT or
MRI provides more structural detail and can sometimes give specific information about
the tissue composition. Foreign bodies are one of the most common causes of nasal
obstruction in children, and some of these will give the appearance of a soft-tissue mass.
A good history and a high index of suspicion are often more useful than imaging with
nasal foreign bodies.
Nasal polyps are the most common nasal masses seen in children. Cross-sectional
imaging shows a round well-defined mass within the nasal cavity. Such masses are of
low to intermediate attenuation on CT and show high signal intensity on T2-weighted
MRI images due to their high fluid content. A similar appearance can be seen with
nasolacrimal duct mucoceles, caused by the incomplete recanalization of the nasolacrimal
duct. Antrochoanal polyps arise within the maxillary sinuses and extend through the sinus
ostia into the nasal cavity. Such polyps cause opacification and enlargement of the
involved sinus, and their extension into the hypopharynx is readily demonstrable with CT
or MRI (Fig. 71.20).

FIGURE 71.20. Antrochoanal polyp. Computed
tomography reveals the totally opacified right maxillary
sinus, with a large soft-tissue mass (arrows) obstructing
the nasal cavity.



Hypertrophied lymphoid tissue in the adenoids and tonsils is the most common cause of
soft-tissue masses obstructing the nasopharynx and oropharynx. Lateral radiographs of
the nasopharynx are usually sufficient to evaluate the size of the adenoids and tonsils; the
adenoids are seen as a prominent convex soft-tissue mass along the posterior
nasopharyngeal wall, and the palatine tonsils can usually be visualized as an oval-shaped
soft-tissue mass adjacent to the tip of the soft palate (Fig. 71.21). However, be aware that
lymphoid tissue tends to be quite generous in older children, and there are no reliable
radiographic criteria for determining when adenoidal and palatine enlargement becomes
pathologic.

FIGURE 71.21. Adenotonsillar hypertrophy. A: Note the
marked enlargement of the adenoids (A), which obliterate
the nasopharyngeal airway. The palatine tonsils (T) are
also enlarged. B: Normal adenoids and tonsils in a 3-
year-old child.



Although uncommon, both benign and malignant neoplasms occur in the nasopharynx in
children, and often their imaging characteristics are nonspecific. One of the most
common benign neoplasms arising in this region is a teratoma, usually arising from the
soft palate or Rosenmller fossa (18). Teratomas are usually large and visible clinically.
Calcification within the mass is very common and can be identified on plain radiographs,
but CT or MRI can better define the extent of such masses.
Juvenile angiofibroma is a rare benign vascular tumor with very characteristic imaging
findings. Radiographs show a large soft-tissue mass in the nasopharynx, usually
associated with anterior bowing of the posterior wall of the maxillary sinus and
displacement of the nasal septum. CT and MRI give superior delineation of the tumor
margins, which often extend into the nasal cavity and adjacent sinuses. Most
angiofibromas originate in the posterior nasopharynx, and the vast majority involve the
pterygopalatine fossa (19). The highly vascular nature of these masses is evident with
contrast-enhanced CT (Fig. 71.22A). Dynamic images obtained during the injection of
contrast show intense enhancement that decreases rapidly on delayed images. The signal
intensity of angiofibroma on MRI varies but generally is high on T2-weighted images. In
addition, areas of signal void can be detected due to blood flow within the numerous
tumor vessels. Although not necessary for diagnosis, angiography is usually performed
for juvenile angiofibromas to precisely delineate the vascular supply of the lesion and to
embolize the major feeding vessels before surgical removal (Fig. 71.22B). Angiomatous
polyps can mimic the appearance of juvenile angiofibromas, but such polyps are less
likely to demonstrate intense contrast enhancement or to involve the pterygopalatine
fossa (20).

FIGURE 71.22. Juvenile angiofibroma of the
nasopharynx. A: Axial postcontrast computed
tomography shows a homogeneously enhancing mass
extending from the right nasal cavity into the maxillary
sinus (arrows). B: Arteriography shows early filling of a
hypervascular mass that is supplied mainly by branches
of the internal maxillary artery (arrow).



Primary malignant tumors that arise in the nasopharynx of children include
rhabdomyosarcoma, lymphoma, nasopharyngeal carcinoma, neuroblastoma, and
malignant germ cell tumors. Rhabdomyosarcoma is the most common malignant tumor
of the nasopharynx, and 40% of all rhabdomyosarcomas occur in the head and neck.
Lymphoma is also quite common in the nasopharynx, most often arising in the region of
Waldeyer ring. Nasopharyngeal carcinoma (usually lymphoepithelial carcinoma) also
tends to arise in this region and can have an identical appearance (21). All
nasopharyngeal malignancies have a similar appearance on CT and MRI. Extension of a
nasopharyngeal soft-tissue mass into the sinuses, orbit, or pterygopalatine fossa suggests
the malignant nature of the lesion. MRI is the preferred modality for the assessment of
malignant tumor because of the superior soft-tissue discrimination and direct multiplanar
imaging capability (Fig. 71.23). However, CT provides better definition of extent of bone
destruction.

FIGURE 71.23. Rhabdomyosarcoma of the
nasopharynx. A: Contrast-enhanced computed
tomography shows marked displacement of the
pharyngeal airway (P) by an ill-defined irregularly
enhancing mass in the lateral pharyngeal soft tissues
(arrows). B: T2-weighted magnetic resonance images
with fat suppression give improved delineation of the
high-intensity tumor (arrows).



Developmental malformations must always be considered in the differential diagnosis of
nasal and nasopharyngeal masses. Most of these lesions occur in the midline of the
nasofrontal region, and they include encephalocele, dermoids, and cerebral heterotopia
(nasal glioma). Radiographs can often identify the midline bone defects that accompany
encephaloceles, including widening of the nasal septum, hypertelorism, and bony defects
in the cribriform plate and between the frontal and nasal bones. Nasal encephaloceles are
easily diagnosed with MRI because of its superior ability to image the herniating tissue in
the sagittal and coronal planes. Nasal gliomas are embryologically related to nasal
encephaloceles, and therefore many of the imaging findings are the same. However,
persistent connection with intracranial structures remains in only 15% of patients with
nasal glioma. Communication between the mass and the subarachnoid space is not well
seen with MRI, but CT performed after the introduction of intrathecal contrast can be
helpful. The contrast will fill an encephalocele, but the communication is usually absent
with nasal glioma (22). Nasal dermoids are predominantly cystic and may contain fat
(Fig. 71.24A). These contents cause dermoids to contain high signal intensity on both T1-
and T2-weighted MRI images. When nasal dermoids are superficial, ultrasound can be
used to identify the anechoic cystic and echogenic fatty components of a dermoid (Fig.
71.24B).

FIGURE 71.24. Nasal dermoid. A: Note the soft-tissue
mass in the right nasal cavity (arrows), with associated
deformity of the nasal septum and nasal bones. B:
Ultrasound of a superficial nasal dermoid reveals its
characteristic cystic appearance (arrows), with internal
echogenic fat.




HIGHLIGHTS
The cause of supraglottic airway obstruction is usually readily
apparent on plain radiographs, particularly epiglottitis.
Airway obstruction can be localized to the level of the glottis
when characteristic changes in caliber and configuration of the
upper airway are seen on inspiratory/expiratory radiographs or
during fluoroscopy. However, the precise cause of glottic
obstruction often cannot be determined radiologically.
Characteristic patterns of subglottic airway narrowing are
detectable on dynamic radiographic imaging, such as the fixed
concentric narrowing seen with subglottic stenosis, expiratory
narrowing with tracheomalacia, and eccentric posterolateral
tracheal narrowing due to subglottic hemangioma.
Foreign bodies lodged in the upper esophagus are a common
unsuspected cause of partial airway obstruction that can be
identified with plain radiographs or barium esophagram.
Retropharyngeal soft-tissue thickening due to retropharyngeal
abscess can be identified on good quality lateral neck
radiographs, but the appearance is frequently indistinguishable
from thickening due to lymphadenopathy or other masses of the
retropharyngeal space. CT and ultrasound are complementary
examinations that can aid in the diagnosis and drainage of such
abscesses.
Ultrasound is the modality of choice for screening neck masses
in children. Lymphadenopathy, abscess, lymphatic
malformation, hemangioma, lipoma, and cysts all have
distinctive sonographic characteristics.
CT is usually the best modality for the evaluation of nasal
obstruction due to congenital abnormalities or masses. Thin
slice thickness provides fine bone detail that is particularly
useful in characterizing the components of choanal atresia.
Lateral radiographs of the upper airway are usually sufficient
for evaluating adenotonsillar hypertrophy, but other
nasopharyngeal masses are better demonstrated with CT or
MRI. MRI provides the best soft-tissue definition and so is
frequently preferred for determining extent of masses, but CT
gives better information about bone expansion or destruction.
Audio-enhanced video-fluoroscopic evaluation of the structure
and function of the velopharyngeal complex is useful for
evaluating children with cleft palate anomaly, previous
nasopharyngeal surgery, or other causes of velopharyngeal
incompetence or obstruction.
CHAPTER REFERENCES
1. John SJ, Swischuk LE. Stridor and upper airway obstruction in infants and children.
Radiographics 1992;12:625643.
2. John SD, Swischuk LE, Hayden CK Jr, et al. Aryepiglottic fold width in epiglottitis. Radiology
1994;190:123125.
3. Wittenberg WH, Gyepes MR, Crocker D. Tracheal dynamics in infants with respiratory distress,
stridor, and collapsing trachea. Radiology 1967;88:653662.
4. Garel C, Hassan M, Legrand I, et al. Laryngeal ultrasonography in infants and children:
pathological findings. Pediatr Radiol 1991;21:164.
5. Hernandez RJ, Tucker GF. Congenital tracheal stenosis: role of CT and high kV films. Pediatr
Radiol 1987;17:192196.
6. Simoneaux SF, Bank ER, Webber JB, et al. MR imaging of the pediatric airway. Radiographics
1995;15:287298.
7. Manson D, Babyn P, Filler R, et al. Three-dimensional imaging of the pediatric trachea in
congenital tracheal stenosis. Pediatr Radiol 1994;24:175179.
8. Brasch R, Gould R, Gooding CA, et al. Upper airway obstruction in infants and children:
evaluation with ultrafast CT. Radiology 1987;165:459466.
9. Cooper M, Slovis TL, Madgy DN, et al. Congenital subglottic hemangioma: frequency of
symmetric subglottic narrowing on frontal radiographs of the neck. AJR Am J Roentgenol
1992;159:12691271.
10. Currarino G, Williams B. Air collection in the retropharyngeal soft tissues observed in lateral
expiratory films of the neck in 9 infants. Pediatr Radiol 1993;23:186188.
11. Ben-Ami T, Yousefzadeh DK, Aramburo MJ. Pre-suppurative phase of retropharyngeal infection:
contribution of ultrasonography in the diagnosis and treatment. Pediatr Radiol 1990;21:2326.
12. Glasier CM, Stark JE, Jacobs RF, et al. CT and ultrasound imaging of retropharyngeal abscesses
in children. AJNR Am J Neuroradiol 1992;12:1191.
13. Glasier GM, Seibert JJ, Williamson SL, et al. High resolution ultrasound characterization of soft
tissue masses in children. Pediatr Radiol 1987;17:233237.
14. Vazquez E, Enriquez G, Castellote A, et al. US, CT, and MR imaging of neck lesions in children.
Radiographics 1995;15:105122.
15. Tadmor R, Ravid M, Millet D, et al. Computed tomographic demonstration of choanal atresia.
AJNR Am J Neuroradiol 1984;5:743745.
16. Crockett DM, Healy GB, McGill TJ, et al. Computed tomography in the evaluation of choanal
atresia in infants and children. Laryngoscope 1987;97:174183.
17. Chinwuba C, Wallman J, Strand R. Nasal obstruction: CT assessment. Radiology 1986;159:503
506.
18. Alter AD, Cove JK. Congenital nasopharyngeal teratoma: report of a case and review of the
literature. J Pediatr Surg 1987;22:179181.
19. Bryan RN, Sessions RB, Horowitz BL. Radiographic management of juvenile angiofibromas.
AJNR Am J Neuroradiol 1981;2:157166.
20. Som PM, Cohen BA, Sacher M, et al. The angiomatous polyp and the angiofibroma: two different
lesions. Radiology 1982;144:329334.
21. Bass IS, Haller JO, Berdon WE, et al. Nasopharyngeal carcinoma: clinical and radiographic
findings in children. Radiology 1985;156:651654.
22. Barkovich AJ, Vandermarck P, Edwards MSB, et al. Congenital nasal masses: CT and MR
imaging features in 16 cases. AJNR Am J Neuroradiol 1991;12:105116.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

72 PEDIATRIC SLEEP-DISORDERED BREATHING
Head & Neck SurgeryOtolaryngology
72




PEDIATRIC SLEEP-DISORDERED BREATHING
MICHAEL D. POOLE
KEVIN S. PEREIRA

M.D. Poole and K.S. Pereira: Department of OtolaryngologyHead and Neck Surgery, University of
Texas Medical School, Houston, Texas.


Epidemiology
Pathophysiology
Evaluation
History
Physical Examination
Laboratory Evaluations
Treatment
Trends in Pediatric Obstructive Sleep Apnea
Chapter References
Sleep-disordered breathing (SDB) in children, encompassing classic obstructive sleep
apnea syndrome (OSAS) and upper airway resistance syndrome (UARS), has many
similarities to the disorder seen in adults, with important differences. The reader is
referred to the chapter on adult sleep apnea for definitions pertaining to airway
obstruction and for descriptions of polysomnography (PSG). In general, obstructive
apnea in children is more amenable to surgical therapy; and most patients can be
managed by adenotonsillectomy, but several complex and controversial issues
surrounding diagnosis and treatment of pediatric SDB remain.
EPIDEMIOLOGY
The prevalence of SDB has been estimated to be as low as 1% or as high as 11% (1,2).
Simple (primary) snoring is likely to be somewhat more common than SDB. Racial and
genetic differences have been observed in the prevalence of this condition, which is
higher in the African-American population than the white population (1,3). Sleep-related
breathing disorders in children encompass three main conditions: primary snoring,
UARS, and OSAS. The latter two, UARS and OSAS, represent the spectrum of nocturnal
upper airway resistance problems that typically are associated with adverse physiologic
or psychological conditions. Table 72.1 highlights the primary similarities and
differences between these conditions. Primary snoring is relatively common in children,
and studies have shown that most children with primary snoring do not progress to
develop SDB when followed over several years (4,5). Because all three disorders may be
considered on a continuum of sleep-related upper airway obstruction, the absolute
distinction between them, in any given patient, may be somewhat arbitrary and may
change depending on the state of the child's airway (e.g., respiratory infection, atopic
swelling) at the time of evaluation.

TABLE 72.1. SLEEP-DISORDERED BREATHING
IN CHILDREN



PATHOPHYSIOLOGY
The etiology and pathophysiology of OSAS in children typically is said to be
multifactorial, with anatomic and neuromuscular abnormalities playing a major role in
the disorder (6,7,8 and 9). Others, however, downplay the role of neuromuscular factors,
because most children with SDB can be cured by correcting anatomic obstructions. The
narrowing of the airway lumen by hypertrophied lymphoid tissue, compliance and
elasticity of the pharyngeal soft tissue, facial morphology, and the physiologic changes
that occur in the pharyngeal dilators during sleep determine the severity of airway
collapse. Patients with dysmorphic constricted craniofacial development, such as Pierre
Robin sequence; Treacher Collin, Apert, and Crouzon syndromes; and those with
neuromuscular abnormalities as in cerebral palsy and anoxic encephalopathy have a
much higher incidence of severe OSAS. The basic physiologic changes in patients with
OSAS occur cyclically during sleep and are due to airway obstruction causing hypoxia
and hypercapnea, which in turn stimulates the peripheral baroreceptors and
chemoreceptors causing cortical or subcortical arousals with return of pharyngeal tone
and respiration. The sleep fragmentation and decreased rapid-eye-movment (REM) sleep
are thought to be responsible for the daytime symptoms of the disorder. Adenotonsillar
hypertrophy plays a major role in the pathogenesis of OSAS in children. The volume of
lymphoid tissue in the upper airway increases from around 6 months of age up to puberty,
with the maximum proliferation occurring in the preschool years, which coincides with
the peak incidence of OSAS in children. Despite this narrowing of the upper airway by
lymphoid tissue, most children do not develop OSAS. A normal child's airway is less
prone to collapse in sleep than an adult airway.
Virtually all investigators and authors agree that pediatric SDB is typically related to
adenotonsillar hyperplasia, with varying degrees of other skeletal and soft-tissue
anatomic factors playing less common or less important roles. Further, most would agree
that increasing the burden of lymphoid tissue in any given patient would increase the
likelihood of SDB or would worsen existing SDB (10). Likewise, in a child with OSAS
and adenotonsillar enlargement, surgeons would predict a response to surgery that was
proportional to the amount of the lymphoid tissue removed. On the other hand, simple
estimations of lymphoid size alone, either by clinical or radiographic evaluation, have
failed to consistently correlate those findings with the severity of SDB (11).
Skeletal factors have been shown to play a role in the genesis of some proportion of the
cases of pediatric SDB. A study measuring maxillary and mandibular growth and
protusion in normal children and those with OSAS found reduced growth in the latter
group. The hyoid bone position too was lower in this group, which was thought to be due
to inferior displacement of the tongue by the large tonsils (9).
Despite the apparent primacy of anatomic factors as being important in SDB and the
remarkable curative response of anatomic (surgical) corrections, several investigators
continue to assert that underlying neurophysiologic factors play a role. Of these
investigators, Marcus et al. (6,7 and 8) have been among the most prolific and suggest
that adenotonsillar hyperplasia appears to precipitate OSAS in children with abnormal
upper airway function. Abnormalities that have been noted in patients with OSAS
include a blunted arousal response to hypercapnea and reduced compliance of upper
respiratory dilators. Becuase these same changes can be induced in patients by sleep
deprivation, hypercapnea, or hypoxia, it seems more reasonable to conclude that most of
those changes are secondary (and perhaps proportionately progressive) to the OSAS
physiologic conditions that are caused by obstructed anatomy. Otherwise, one would
have to propose that most children with SDB are unfortunate enough to have two
disorders: relative lymphoid hyperplasia and an underlying neuromuscular disorder.
Rather, a more likely scenario is that the complexities in the types of anatomic
obstructions that might be seen in SDB currently exceed our ability to consistently define
them (12).
One of the hallmarks of SDB is fragmentation and disruption of normal sleep
architecture. By definition, deeper levels of sleep, especially REM sleep, are less prone to
arousal from various stimuli, including adverse ventilatory events (13). Oxyhemoglobin
desaturations therefore tend to be more frequent and more severe during REM sleep. The
hypercapnea and hypoxemia and the resulting arousals that are associated with SDB, at
least in part, often result in a reduction in REM sleep (14). Affecting not only the quality
of the sleep, a reduction in REM and slow-wave sleep in SDB is associated with a
reduction in the production of growth hormones, an effect that quickly reverses with
successful therapy (15).
Although SDB and hypertension are commonly associated in adults, few realize that
children with OSAS also tend to have higher diastolic blood pressures. The
cardiovascular changes appear to be the result of an increase in sympathetic tone that
results from the sleep arousals that in turn are related to the obstructive respiratory events
(16).
The clinical presentation of SDB in children has many similarities and important
differences when compared with the disorder in adults (Table 72.2). Snoring is the most
distressing symptom in children, in contrast to daytime hypersomnolence and fatigue in
adults. The reason for this difference may be that children typically have less sleep
fragmentation than adults with OSAS where an apneic episode is usually terminated by
an arousal. Children often exhibit episodes of partial airway obstruction associated with
hypoxemia and hypercapnea during REM sleep manifested by loud snoring and
occasional pauses in breathing. Instead of excessive daytime sleepiness, they may display
hyperactivity, attention deficit, aggression, and other behavioral disorders. Mouth
breathing and a hyponasal speech with articulatory errors are commonly observed in
children with SDB secondary to adenotonsillar hypertrophy. Certain phonemes require
nasal escape that cannot occur in an obstructed nasopharynx.

TABLE 72.2. DIFFERENCES BETWEEN ADULT
AND CHILDHOOD SLEEP-DISORDERED
BREATHING



SDB has been shown to effect school performance in children. A recent study of 297
first-grade children whose performance was in the lowest 10th percentile of their class
identified sleep-associated gas exchange abnormalities in 18% and primary snoring in
22% (17). Therapeutic intervention resulted in significant improvement in school grades.
A high prevalence of allergy has also been demonstrated in children with habitual snoring
(18). The upper airway allergy causes edema of the nasal mucosa with increased
secretions and thereby predisposes children to airway obstruction during sleep.
Nocturnal enuresis is frequently reported in children with OSAS. The exact reason for
this is unclear, although several hypotheses have been postulated. Increased production of
atrial naturetic hormone, decreased activity of the rennin-angiotensin-aldosterone system,
increased production of catecholamines causing altered muscle tone in the bladder, and
higher arousal thresholds have been implicated as being the cause of this symptom (19).
Treatment for the sleep disorder generally results in resolution of enuresis (20). Failure to
thrive that resolves after treatment has been documented in children with OSAS (21,22).
The mechanism for poor height and weight gain is thought to be due to either alone or a
combination of poor appetite, impaired growth hormone secretion, increased energy
utilization by disordered breathing, and the central effects of hypercarbia and acidosis.
Unlike the situation in adults, obesity is not a common factor in pediatric SDB, although
its role increases with the age of the child (23). Abnormal sleep positions with preference
for an upright position and hyperextension of the neck have been noted in children with
sleep-related breathing disorders (22). These positions are thought to be due to a
subconscious effort to maintain an adequate airway during sleep. Excessive sweating may
occur due to increased respiratory effort and as a response to hypercapnea, which causes
vasodilation. Prolonged exposure to hypoxia and hypercarbia results in compensatory
changes in the pulmonary vasculature. Pulmonary vascular resistance increases, causing
increased right ventricular strain. Severe cases may progress to pulmonary hypertension,
arrythmias, and cor pulmonale.
EVALUATION
History
The clinical presentation of OSAS in children has many similarities and important
differences when compared with the disorder in adults (Table 72.2). In children and
adults, a thorough sleep history is appropriate in the evaluation of SDB.
A complete history should exclude any general medical or surgical conditions that may
contribute to the disorder. The sleep history includes the typical bedtime, number of
hours of sleep, abnormal sleep positions, parasomnias (such as sleep walking or sleep
terrors), the character of snoring, observed pauses in respiration and signs of respiratory
distress, problems after waking up such as headaches and fatigue, behavioral disorders,
school performance, and hypersomnolence. Daytime naps and their duration should also
be documented and compared with normal values for age.
Physical Examination
General physical parameters are typically measured: height, weight, and blood pressure.
The child should be observed during the examination, and the pattern and route of
breathing whether oral or nasal should be noted. Craniofacial and neuromuscular
abnormalities should be documented. The oral and oropharyngeal examination should
assess dental malocclusion, pharyngeal soft tissue anatomy, lingual shape and size
relative to the oropharyngeal airway, the shape of the hard and soft palates, the size of the
uvula, velopharyngeal function, and the degree of tonsillar enlargement. Table 72.3 lists
levels and types of upper airway obstruction, and Table 72.4 lists syndromes with
increased rates of SDB.

TABLE 72.3. LEVELS AND TYPES OF
OBSTRUCTION IN PEDIATRIC SLEEP-
DISORDERED BREATHING



TABLE 72.4. SYNDROMES AND CONDITIONS
ASSOCIATED WITH PEDIATRIC SLEEP-
DISORDERED BREATHING



The distances between the medial surfaces of the tonsils, the distance between the lateral
pharyngeal walls, and the relationship of the soft palate to the posterior pharyngeal wall
is observed. A flexible endoscopic examination of the nasal cavity and postnasal space
could reasonably be attempted in most children. Attention is paid to the nasal septum,
mucosa, mid-nasal space, choanal width, and adenoid enlargement. The chest is
examined to rule out chest wall and thoracic spine abnormalities (i.e., pectus excavatum,
scoliosis) that may contribute to or aggravate any sleep-related breathing disorder.
Laboratory Evaluations
PSG remains the gold standard for the diagnosis of OSAS in adults and children. In 1995,
the American Thoracic Society adopted guidelines for performing PSG in children (24).
It was recommended to differentiate primary snoring (that does not require any form of
treatment) from OSAS, which if left untreated can lead to cardiopulmonary dysfunction
and other functional sequelae. In general, studies have shown that history alone does not
have a sufficiently high diagnostic sensitivity or specificity to be the basis for
recommending therapy (25).
A recommendation that PSG be performed on all children being considered for surgery of
SDB is problematic from several standpoints, not the least being the frequency and
costgiven the prevalence of children that might present with either primary snoring or
SDB. There are certain biases intrinsic to the recommendation: The sleep experts are
almost all professional polysommnographers and sleep laboratory directors, with obvious
potential conflicts of interest and unintentional biases. The numerical parameters derived
from sleep studies have been used to define the disease syndromes, when each patient
may have other mitigating findings as part of their clinical picture of airway obstruction
(e.g., recurrent rhinosinusitis, otitis media, pharyngotonsillitis, chronic mouth breathing,
or hyponasal speech). Further, many studies used only patient histories (and not a skilled
examination) in the correlations with PSG. One of the more recent studies showed a 70%
concordance between the referring physician's diagnosis and the sleep study, and no
children with moderate or severe OSAS were missed by clinical examination (which was
not likely as consistently thorough as recommended above). Yet the authors' conclusion
was that PSG still provided useful additional information (26). Another recent study
suggests that clinical parameters, if assessed and weighed correctly can accurately predict
the presence or absence of OSASeven in adults (where the diagnosis may be more
difficult than in children). These investigators fed the data into a trained computerized
neural network that actually made the prediction (27). In reality, it appears that given a
population of patients presenting with SDB, a skilled clinician can accurately predict that
some (with classic and obvious findings) have overt disease, that some patients with
minimal findings do not have SDB, and that a number of patients are difficult to
differentiate between having primary snoring or SDB. Of the latter indeterminate group,
some will benefit from treatment because of coexisting problems. It is therefore our
opinion that skilled and knowledgeable clinicians are given substantial latitude in their
decision as to whether or not to order a PSG in any given patient.
Overnight PSG can be performed at home or in the sleep laboratory. At home, a seven-
channel recording system is typically used. This includes electrocardiography, pulse rate,
oxyhemogoblin saturation, pulse wave form, and calibrated inductive plethysmography.
This compares with 21 channels typically recorded in a sleep laboratory (28). The sleep
laboratory, in addition to the home study channels, includes an electroencephalogram,
electrooculogram, submental electromyogram, oral/nasal airflow, end-tidal CO
2
,
transcutaneous oxygen, and at times intercostal, abdominal, and arm myograms.
However, the architecture of sleep in the laboratory may differ from the normal sleep
pattern with a decrease in total sleep time and reduced REM sleep. The relevance of this
phenomenon (called the first-night effect) in children with OSAS is not known.
Normal values for the various respiratory events have been reported by Marcus et al. (29)
in a study of 50 normal children. The apnea indices were 0.1 0.5, with the minimum
oxygen saturation being 96%, maximal drop in saturation 4%, and a CO
2
of over 55 mm
Hg no more than 0.5% of the total sleep time. Using normative data, the criteria for an
abnormal study were determined: an apnea index of more than 1, oxygen desaturation of
more than 4% more than three times an hour or associated with a greater than 25%
change in heart rate, oxygen desaturation less than 92%, and elevation of end-tidal CO
2
to
more than 50 mm Hg for more than 8% of total sleep time or 45 mm Hg for moe than
60% of sleep time (24,30,31).
A number of abbreviated studies have been examined as possible replacements to PSG.
Daytime nap PSGs and nocturnal oximetry have a fair positive predictive value but
cannot exclude the presence of significant SDB. Audio and/or video recordings and their
analyses are reasonably accurate in identifying obviously overt OSAS or normal patients
but have problems differentiating primary snoring from less severe SDB.
Lateral soft-tissue radiographs are sometimes ordered when adenoid enlargement is
suspected as the cause of nasal obstruction or snoring. This study has limited usefulness,
and flexible endoscopy provides the best assessment of the nasopharynx and its soft
tissues.
Cephalometric studies and computed tomography can provide accurate measurements of
distances between bony landmarks and are useful when evaluating children with
craniofacial abnormalities and syndromes. However, they have a limited role in the
routine evaluation of a child with suspected OSAS. An interesting recent study reported
the use of an orocraniofacial scale to help identify children with similar craniofacial
features that predisposed them to SDB (32). The common features noted were a small
chin, a steep mandibular plane, retrognathia, long face, arched hard palate, and long soft
palate. A scoring system was used wherein the higher scores correlated with more severe
degrees of orofacial dysmorphism. The tonsils were evaluated on a separate scale. The
study found that high scores on both the orocraniofacial and tonsil scales correlated with
OSAS, a high score on only one scale with UARS, and low scores on both scales with no
SDB.
TREATMENT
Medical therapy of pediatric OSAS is not considered to be consistently effective.
Management of allergies and anterior nasal obstruction may result in improvement in
allergic children, but these children are not the ones who are affected most severely and
in need of definitive therapy. Systemic or topical steroids may shrink lymphoid tissue
(33), but the long-term effectiveness is not known, and a short course of systemic
corticosteroids appears to be ineffective (34). Some cases may improve with long-term
use of antibiotics.
Adenotonsillectomy remains the mainstay of treatment for pediatric OSAS (35,36).
Occasionally adenoidectomy alone, particularly in a younger child, or a tonsillectomy
alone, usually in an older child, may relieve the important obstruction. Most practitioners
report a high recurrence rate of obstructive symptoms if either operation is performed
alone in an attempt to limit the scope of the procedure. There may be a compensatory
hyperplasia of the remaining lymphoid tissue.
The optimal age for adenotonsillectomy is probably between 4 and 7 years, yet young
age, even less than 1 year, is not a contraindication for surgery for airway obstruction or
sleep apnea. The maintenance of adequate oral intake postoperatively is more difficult in
the younger patient, and there is a more delayed postoperative bleeding in the older
patient. A complete adenoidectomy in the young child with OSAS can prevent the
adenoidal regrowth that is usually caused by an incomplete procedure. Inspection of the
nasopharynx with an angulated mirror is important in ensuring removal of the adenoid
remnants obstructing the superior nasopharynx and posterior choanae. Removal of
obstructing adenoids in the patient aged over 5 years is usually technically more
challenging than in the young child and infant, despite conventional wisdom and
reimbursement strategies that imply the opposite.
With the increasing use of lasers and other forms of heat delivery to soft tissues, we can
expect great interest in techniques that reduce or ablate lymphoid tissue without the need
for general anesthesia or complete adenotonsillectomy.
Children with Down syndrome deserve further comment because they frequently have
severe OSAS (37). Although there are conflicting data on the usefulness of
adenotonsillectomy in this group, it appears worthwhile if the tonsils or adenoids are
obstructing the airway. If an adenotonsillectomy fails or is not considered appropriate
therapy, uvulopalatopharyngoplasty may be effective (5). Uvulopalatopharyngoplasty is
not indicated for the usual child with OSAS.
Patients who have undergone repair of velopharyngeal incompetence with a pharyngeal
flap are at risk for OSAS because of nasopharyngeal obstruction. In this group, the
nocturnal airway obstruction may be silent, without snoring, because of the fixation of
the palate.
A degree of variation remains in the management of children undergoing
adenotonsillectomy for OSAS. Several studies demonstrated the relative safety of this
procedure performed on an outpatient basis with a suitable period of postoperative
observation and hydration. After a modest number of procedures, surgeons can appreciate
that certain groups of children are at higher risk for postoperative complications
(respiratory, inadequate oral intake) and failure to meet discharge criteria: children of
young age, syndromic children, those with severe sleep apnea, or those with coexisting
medical problems. A number of institutions have used those observations to justify the
routine inpatient postoperative status (even in the intensive care unit) of virtually all
children with sleep apnea undergoing adenotonsillectomy. Alternatively, it appears that if
children meet standard discharge criteria (normal respiratory parameters, no bleeding,
adequate oral intake and pain control, and normal mental status) at 4 to 6 hours after
surgery, they can be safely discharged home regardless of age or preoperative diagnoses.
Data that answered questions concerning the occurrence of respiratory problems in
certain groups were used inappropriately to try to answer the question under what
circumstances can a child with OSAS who underwent adenotonsillectomy be discharged?
The answers are quite different.
Postobstructive pulmonary edema has developed in some children undergoing
adenotonsillectomy for relief of upper airway obstruction. The incidence of this
complication is unknown; it has occurred in less than 1% of our patients. This potentially
life-threatening problem is often manifested immediately on orotracheal intubation and is
obvious within several hours of surgery. We are aware of no patients who would have
been missed by routine postoperative care. It is manifested by increasing respiratory
distress, tachypnea, oxyhemoglobin desaturations, and increased secretions. Like other
forms of pulmonary edema, it is adequately managed with fluid restriction, diuresis
(furosemide), and endotracheal intubation with application of continuous pulmonary
artery pressure in more critically ill patients.
TRENDS IN PEDIATRIC OBSTRUCTIVE SLEEP APNEA
Pediatric SDB is a relatively new clinical diagnosis, existing for less than 20 years, and it
is now the most common reason for adenotonsillectomy in the young child. It may be that
our urban population is faced with a relative epidemic of adenotonsillar enlargement
related to early infection with multiple respiratory pathogens (viral and bacterial) that
induce hyperplasia. Causal factors, the natural history, and less invasive methods for
dealing with the lymphoid disease are all areas ripe for investigation.
Several studies are in progress that will shed light on the optimal methods for
perioperative management of children with OSAS and related problems. Clearly,
outpatient management of selected children is appropriate. Otolaryngologists face an
urgent need to improve our base of sound clinical and epidemiologic data relating to
these common and significant problems.

HIGHLIGHTS
Upper airway obstruction and sleep apnea in children has many
similarities to the syndrome in adults, but there are important
differences.
The history pertinent for airway obstruction in the pediatric
patient may be correspondingly more important than for adults
with suspected obstructed sleep apnea, because the history, in
combination with the anatomic findings on the physical
examination, may be enough to support surgical treatment in
children.
One of the most interesting and important sequelae of pediatric
OSAS, the one that should alert clinicians to the overall
importance of the diagnosis, is the growth (i.e., height and
weight) delay that may be attributed to upper airway
obstruction.
Any craniofacial abnormality resulting in a small
underdeveloped maxilla or mandible is likely to increase the
possibility of significant airway obstruction.
Fiberoptic endoscopy should be considered the gold standard of
diagnostic tests for adenoidal hyperplasia and probably for
obstruction due to tonsillar enlargement.
Medical therapy of pediatric OSAS is not considered to be
consistently effective.
Children with Down syndrome frequently have sleep apnea.
Postobstructive pulmonary edema has developed in some
children undergoing adenotonsillectomy for relief of upper
airway obstruction.
Pediatric OSAS is a relatively new clinical diagnosis that has
existed for fewer than 15 years; it is now the most common
reason for adenotonsillectomy in the young child.
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8. Marcus CL, Moreira GA, Bamford O, et al. Response to inspiratory resistive loading during sleep
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healthy children. Pediatr Pulmonol 1999;27:403409.
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12. Finkelstein Y, Wexler D, Berger G, et al. Anatomical basis of sleep-related breathing
abnormalities in children with nasal obstruction. Arch Otolaryngol Head Neck Surg
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with obstructive sleep apnea. J Appl Physiol 1998;84:19261936.
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night. Am J Respir Crit Care Med 1998;157:A533.
15. Bar A, Tarasiuk A, Segev Y, et al. The effect of adenotonsillectomy on serum insulin-like growth
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Respir Crit Care Med 1998;157:10981103.
17. Gozal D. Sleep-disordered breathing and school performance in children. Pediatrics
1998;102:616620.
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21. Everett AD, Koch WC, Saulsbury FT. Failure to thrive due to obstructive sleep apnea. Clin
Pediatr 1987;26:9092.
22. Lind MG, Lundell BP. Tonsillar hyperplasia in children. A cause of obstructive sleep apneas, CO
2

retention and retarded growth. Arch Otolaryngol 1982;108:650654.
23. Mallory GB, Fiser DH, Jackson R. Sleep associated breathing disorders in morbidly obese
children and adolescents. J Pediatr 1989;115:892897.
24. American Thoracic Society. Standards and indications for cardiopulmonary sleep studies in
children. Am J Respir Crit Care Med 1996;153:866878.
25. Carroll JL, McColley SA, Marcus CL, et al. Inability of clinical history to distinguish primary
snoring from obstructive sleep apnea syndrome in children. Chest 1995;108:610618.
26. van Someren V, Burmester M, Alusi G, et al. Are sleep studies worth doing? Arch Dis Child
2000;83:7681.
27. Kirby SD, Eng P, Danter W, et al. Neural network prediction of obstructive sleep apnea from
clinical criteria. Chest 1999;116:409415.
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syndrome secondary to adenotonsillar hypertrophy. Pediatr Pulmonol 1995;20:241252.
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30. American Thoracic Society. Cardiorespiratory sleep studies in children. Establishment of
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Pediatrics 1996;98:871882.
33. Craig TJ, Teets S, Lehman EB, et al. Nasal congestion secondary to allergic rhinitis as a cause of
sleep disturbance and daytime fatigue and the response to topical nasal corticosteroids. J Allerg
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

73 LARYNGEAL STENOSIS
Head & Neck SurgeryOtolaryngology
73




LARYNGEAL STENOSIS
MICHAEL J. RUTTER
ROBIN T. COTTON

M.J. Rutter and R.T. Cotton: Department of Pediatric Otolaryngology, Children's Hospital Medical
Center, Cincinnati, Ohio.


Pediatric and Adult Anatomy
Laryngeal Size
Laryngeal Location
Laryngeal Stenosis
Congenital Laryngeal Stenosis
Acquired Laryngeal Stenosis
Infectious or Inflammatory Stenosis
Differential Diagnosis
Management
Natural History
Medical Therapy
Preoperative Assessment
Surgical Treatment
Anterior Cricoid Split
Laryngotracheal Reconstruction
Cricotracheal Resection
Stenting Options
Decision Making
Complications
Emergencies
Chapter References
Congenital or acquired laryngeal stenosis can present as a life-threatening situation or
may convert to a life-threatening situation by inappropriate management. To understand
laryngeal stenosis, the physician must first understand the anatomy and embryology of
the region. The clinician must also have an organized differential diagnosis in mind to
make the correct diagnosis and provide appropriate management.
PEDIATRIC AND ADULT ANATOMY
The three portions of the larynx are the supraglottis, glottis, and subglottis. These
laryngeal components are the same in adults and children. However, some age-related
differences play a role in the development of laryngeal stenosis.
Laryngeal Size
The infant larynx is approximately one third the size of the adult larynx, but it is
proportionally larger than the adult larynx compared with the rest of the tracheobronchial
system. The infant vocal cord is approximately 7 to 8 mm long, and the adult vocal cord
is 14 to 23 mm long. In the infant, half of the length of the true vocal cord is composed of
the vocal process of the arytenoid. In the adult, the vocal process occupies only one
fourth to one third of the total length of the true vocal cord. Because of the complete ring
structure of the cricoid, the subglottis is the narrowest part of the airway. In the infant, the
subglottis is approximately 4.5 to 7 mm. In a full-term infant, subglottic stenosis is
present if the cricoid area of the airway measures less than 4 mm.
Laryngeal Location
The position of the larynx in relation to other structures of the neck is different in infants
and adults. In the infant, the superior border of the larynx is located as high as the first
cervical vertebra, with the cricoid cartilage positioned at approximately the level of the
fourth cervical vertebra. This results in the hyoid overriding the superior larynx in an
infant, with the thyroid notch usually being impalpable as a consequence. Because of the
superior positioning of the larynx, the epiglottis approximates the dorsal surface of the
soft palate. This explains obligate nasal breathing in the first months of life (see Chapter
4). As the child grows into adulthood, the larynx gradually descends, and the cricoid
cartilage eventually rests at the level of the sixth cervical vertebra. The infant epiglottis is
the structure that demonstrates the most dramatic change in configuration. At birth, the
epiglottis, which is shaped like the Greek letter omega (), is narrower and softer than
that found in older children and adults. It has a less stable base, and there is a more acute
angle between the epiglottis and glottis, allowing the epiglottis to fall into the laryngeal
inlet. As the child grows, cartilaginous support of the epiglottis becomes more rigid, and
the angle of the thyroid cartilage changes from 110 to 120 degrees to an angle of 90
degrees in the adolescent male. In the adult female, this angulation remains more obtuse,
as in childhood. Because cartilage, muscle, and submucosal tissues are more pliable and
less fibrous in the infant than in the adult and because the airway is so narrow at the
subglottis, any process that produces edema can cause significant airway obstruction.
Circumferential mucosal edema of 1 mm within the larynx of an infant narrows the
subglottic space by more than 60% (1). Within the fixed ring of the cricoid cartilage,
edema will cause a marked diminution in potential airflow (Poiselleure's law stating that
flow is inversely proportional to radius
4
).
LARYNGEAL STENOSIS
Laryngeal stenosis may occur in the supraglottis, glottis, or subglottis. Clinically,
subglottic stenosis is by far the most common problem requiring intervention, followed
by glottic stenosis. Supraglottic stenosis is rare in children and usually is a consequence
of thermal or chemical injury or iatrogenic injury after previous airway reconstructive
surgery. Evaluation of congenital stenosis of the larynx can often be determined by the
signs and symptoms of obstruction. Supraglottic, glottic, and subglottic laryngeal lesions
provide different signs and symptoms (Table 73.1) that help the clinician in the initial
assessment of the patient.

TABLE 73.1. SIGNS AND SYMPTOMS OF
LARYNGEAL STENOSIS



Supraglottic laryngeal obstruction produces a muffled or throaty voice with an inspiratory
fluttering stridor. This patient may present with significant feeding problems but no
cough. Children with supraglottic stenosis are among the most challenging patients to
manage, with their stenosis often further complicated by dynamic supraglottic collapse.
An individualized approach to management is essential in these difficult patients.
Congenital Laryngeal Stenosis
Subglottic Stenosis
Subglottic stenosis in the neonate is defined as a lumen less than 4 mm in diameter at the
level of the cricoid. A relevant reference point is the outer diameter of an endotracheal
tube3.6 mm for a 2.5 (mm inner diameter) endotracheal tube and 4.2 mm for a 3.0
endotracheal tube. It is important to differentiate congenital from acquired subglottic
stenosis. Acquired subglottic stenosis is caused by intubation or other forms of laryngeal
trauma, is a complication of medical therapy, and is generally more severe, requiring
aggressive long-term management. This type of stenosis is covered later in this chapter.
In the absence of trauma, an abnormality of the cartilage or subglottic tissues is usually
considered to be congenital. The cause of congenital subglottic stenosis is thought to be a
failure of the laryngeal lumen to recanalize (2). Congenital subglottic stenosis lies on a
continuum of embryologic failures that includes laryngeal atresia, stenosis, and webs. In
its mildest form, congenital subglottic stenosis merely represents a normal-appearing
cricoid with a smaller than average diameter, usually with an elliptical shape.
A mild case of subglottic stenosis may produce a clinical picture of recurrent upper
respiratory infections, often diagnosed as croup, in which minimal glottic swelling
precipitates airway obstruction. The greatest obstruction is usually 2 to 3 mm below the
true vocal cords.
More severe cases of congenital subglottic stenosis may cause life-threatening situations
at delivery. If endotracheal intubation is successful, the patient may require intervention
before extubation. In more severe cases, if the diagnosis is made in time, tracheotomy can
be life saving at the time of delivery. However, infants with congenital subglottic stenosis
may have surprisingly few symptomseven grade III subglottis stenosis may not present
for weeks or months.
Congenital subglottic stenosis is often associated with other congenital head and neck
lesions and syndromes (e.g., small larynx in Down syndrome). After the initial
management of congenital subglottic stenosis, the larynx will grow with the patient and
may not require further surgical intervention. Holinger et al. (3) reported that most
children with congenital narrowing can be decannulated by 24 to 36 months of age.
Congenital subglottic stenosis can be divided histopathologically into membranous and
cartilaginous types (1) (Table 73.2). The membranous type is usually circumferential and
presents as a fibrous soft-tissue thickening in the subglottis caused by increased fibrous
connective tissue or hyperplastic mucous glands. It usually includes the area 2 to 3 mm
below the true vocal cords, but it may extend upward to include the true cords. The
cartilaginous type commonly presents as a thickening or deformity of the cricoid cartilage
that creates a shelflike plate of cartilage on the inner surface of the cricoid ring, extending
posteriorly as a solid sheet and leaving only a small posterior opening. Stenosis may also
be caused by a trapped first tracheal ring.

TABLE 73.2. HISTOPATHOLOGIC
CLASSIFICATION OF SUBGLOTTIC STENOSIS



Although the histopathologic picture may vary, the diagnosis of subglottic stenosis is
based on endoscopic assessment. The stenosis due to a scar, granulation tissue,
submucosal thickening, or a congenitally abnormal cricoid can be differentiated from
subglottic stenosis with a normal cricoid, but endolaryngic measurement with
endotracheal tubes or bronchoscopes is required for an accurate diagnosis. Many
laryngeal stenoses represent a combination of a congenitally small larynx further
traumatized by endolaryngeal intubation or instrumentation.
Radiologic evaluation of a patient's unintubated airway may give the clinician clues about
the site and length of the stenosis. Useful imaging modalities include inspiratory and
expiratory lateral soft-tissue neck films, fluoroscopy to demonstrate the dynamics of the
trachea and larynx, and a chest x-ray. However, the single most important investigation
remains high-kilovoltage airway films to look for the classic steepling seen with
subglottic stenosis but also to provide warning of tracheal stenosis, usually due to
complete tracheal rings, which may place the child in a life-threatening situation during
rigid endoscopy.
Endoscopy is necessary for the diagnosis of laryngeal stenosis. Flexible fiberoptic
endoscopy provides information on dynamic vocal cord function. Rigid endoscopy with
Hopkins telescopes provides the best possible examination. Precise measurement of the
endolarynx and staging of the laryngeal stenosis can be carried out (Table 73.3), although
no staging system is universally accepted.

TABLE 73.3. GRADING SCALE FOR
LARYNGEAL STENOSIS



Atresia
Supraglottic atresia represents the most severe failure of embryologic formation of the
supraglottic larynx. It is associated with a high frequency of other congenital anomalies,
including esophageal atresia, tracheoesophageal fistula, urinary tract anomalies, and limb
defects, particularly involving the radius. If a tracheoesophageal fistula exists, ventilation
may occur through this communication. Tracheotomy is essential if the patient is to
survive. Many children are not properly diagnosed in time for the appropriate
intervention, and the diagnosis may be made postmortem.
Laryngeal atresia represents complete failure to recanalize the lumen of the larynx and
therefore represents the most severe form of laryngeal stenosis. A concomitant
tracheoesophageal fistula may sustain respiration long enough for tracheotomy to be
performed.
Webs
Supraglottic webs represent fewer than 2% of congenital laryngeal webs (4). These webs
are diaphragmatic outgrowths that usually arise anteriorly. If partial, they provide air
passage posteriorly. The web is customarily thickened anteriorly and thins out toward the
posterior edge. Symptoms, including dyspnea and voice change, depend on the size and
position of the web. Ten percent of children with webs have associated congenital
anomalies.
Glottic webs, representing a failure to completely recanalize the larynx, usually present
with an abnormal cry or respiratory distress at birth. Virtually all glottic webs are
anterior, with varying degrees of compromise of the glottic airway. Ninety percent of
laryngeal webs are located at the level of the glottis. Although some webs are gossamer
thin, most anterior glottic webs are thick and usually associated with a subglottic sail
compromising the subglottic lumen. Thin webs may escape detection because neonatal
intubation for airway distress may lyse the web. Thick webs require open reconstruction
with either reconstruction of the anterior commissure or placement of a laryngeal keel.
Thick membranous webs require tracheotomy in approximately 40% of the patients (4).
There is a strong association between anterior glottic webs and velocardiofacial
syndrome.
A web can also form in the subglottic region, mimicking cricoid cartilage deformities or
subglottic stenosis. Subglottic webs account for approximately 7% of laryngeal webs and
are anteriorly based, with a small posterior opening that may be only the size of a
pinpoint. The superior surface is covered with squamous epithelium, and the inferior
surface is mucous membrane. A slight female predominance has been reported.
Symptoms include aphonia, respiratory distress, and biphasic stridor. Diagnosis must be
made by flexible fiberoptic or rigid endoscopy.
Acquired Laryngeal Stenosis
Postintubation Stenosis
In 1965, McDonald and Stocks (5) advocated long-term nasotracheal intubation in the
management of the unstable neonatal airway. Although this revolutionized neonatal care,
especially for the premature infant, there was a corresponding increase in the incidence of
acquired subglottic stenosis in neonatal intensive care unit graduates. The incidence of
combined congenital and acquired subglottic stenosis also rose as infants with congenital
subglottic stenosis were intubated for airway compromise, often with inappropriately
large endotracheal tubes. Acquired subglottic stenosis resulting from prolonged neonatal
intubation is now more common than congenital stenosis in the pediatric age group.
The pathogenesis of acquired subglottic stenosis is still not understood, although there are
several theories. Autopsy studies demonstrate a period of ulceration and necrosis of
cricoid mucosa in the first hours and days of intubation (5). Quiney and Gould (6) report
healing and reepithelialization in the cricoid region, even while the endotracheal tube
remained in place. However, 1% to 8% of neonates develop stenosis after prolonged
intubation (7,8). The incidence has steadily dropped over the last 3 decades despite the
longer periods of intubation that have become commonplace in increasingly smaller
infants. Although several factors are involved, the two most significant have been the
abandoning of red rubber endotracheal tubes and the realization that the ideal
endotracheal tube size is not the largest that will fit but rather the smallest that can permit
adequate ventilation. Ideally, an endotracheal tube should leak air around it with
subglottic pressures below 25 to 30 cm H
2
O.
Flexible fiberoptic laryngoscopy should be a routine part of the initial evaluation of the
larynx. Vocal cord paralysis may prohibit decannulation, even after successful surgical
reconstruction of a compromised airway. Rigid endoscopy using Hopkins telescopes is
necessary for diagnosis and photodocumentation. Correct sizing of the airway should be
done with appropriately sized endotracheal tubes or rigid bronchoscopes. Before any
form of management, radiological assessment can provide information about the site and
length of the stenosis. In acquired stenosis, a prolonged period of observation after
tracheotomy is inappropriate because of the potential mortality if the tracheotomy tube
becomes obstructed.
Postoperative Stenosis
Sasaki et al. (9) studied dogs that had subglottic mucosal injury followed by tracheotomy,
and they demonstrated significant bacterial contamination of the subglottis from the
tracheotomy site that led to chronic mucosal ulceration and subsequent chondritis. This
same subglottic injury without the influence of tracheotomy healed without infection.
This may partially explain the cause of subglottic stenosis or suprastomal stenosis after
tracheotomy.
Jackson (10) described 158 of 200 children referred to him for chronic laryngeal stenosis,
which he thought was due to the practice of high tracheostomies and improper
tracheotomy care. A high tracheotomy is one that is performed through the thyroid,
cricoid, or first tracheal cartilages, and includes cricothyroidotomy. This procedure is
well known to otolaryngologists and emergency room physicians as a life-saving
procedure. In 1976, Brantigan and Grow (11) presented 655 cases of cricothyroidotomy
with a complication rate of 6.1%, including no cases of chronic subglottic stenosis. Many
reports have followed, including 2 patients with glottic or subglottic stenosis from a
group of 105 survivors of cricothyroidotomy and 5 patients with subglottic stenosis
among 76 patients undergoing cricothyroidotomy (12,13). McGill et al. (14), analyzing
the cricothyroidotomies done in an emergency setting, found a complication rate of 32%,
which was five times the original complication rate reported by Brantigan and Grow (11).
Nevertheless, no cases of chronic subglottic stenosis were reported. In 1987, Esses and
Jafek (15) reported 948 tracheotomies and 78 cricothyroidotomies. Two (2.6%) cases of
subglottic stenosis were reported for the cricothyroidotomies. Based on these findings,
Esses and Jafek (15) did not recommend performing cricothyroidotomy in pediatric
patients if an endotracheal tube had been in place for more than 7 days or if there was
laryngeal inflammation or infection.
Subglottic stenosis may also result after failed laryngotracheoplasty. This is more likely
to occur if the original procedure was not aggressive enough or there is concomitant
bacterial infection, development of granulation tissue, malalignment or improper stent
sizing, or histopathologic changes. Indeed, any form of airway surgery, both endoscopic
and open, has an attendant risk of resultant airway restenosis. This is exacerbated if there
is an active larynx, most commonly associated with gastroesophageal reflux disease.
Infectious or Inflammatory Stenosis
Laryngeal stenosis caused by infectious or inflammatory disorders is usually the result of
end-stage processes of untreated disease.
Granulomatous Disease
Tuberculosis of the larynx is the most common granulomatous disease of the larynx, and
it is usually associated with pulmonary disease. The most common sites for laryngeal
tuberculosis are the interarytenoid space, arytenoid cartilages, posterior surface of the
true vocal cords, and laryngeal surface of the epiglottis. The patient may present in the
early stages of disease with diffuse edema and erythema of the cords, which may mimic
an early stage glottic carcinoma. However, disease progression manifests nodular lesions
and ulceration of the epithelium, which can lead to perichondritis and chondritis. The
patient may also present mimicking vocal cord paralysis due to interarytenoid muscular
involvement or cricoarytenoid joint fixation. Diagnosis is made by demonstration of
Mycobacterium tuberculosis. Successful treatment usually leads to complete healing of
the larynx. If the disease is not treated, chrondritis and necrosis will destroy the larynx
with extensive scarring and stenosis.
Sarcoidosis, rhinoscleroma and Wegener granulomatosis are all rare disorders in children.
Wegener granulomatosis may respond well to steroids, cyclophosphamide, and possibly
co-trimoxazole. Wegener granulomatosis has a predilection for the subglottis and, once
quiescent, may require airway reconstruction with cricotracheal resection being
potentially more efficacious than standard laryngotracheal reconstruction using expansion
cartilage grafting.
Trauma
Laryngeal trauma is covered in Chapter 63, and only brief comments are made here.
Trauma may lead to laryngeal stenosis if mismanaged or undiagnosed. Sources of
internal trauma include foreign bodies and instrumentation during endoscopic procedures.
These forms of trauma usually lead to glottic and subglottic scarring and resultant
stenosis. External forms of laryngeal trauma, such as motor vehicle accidents, sports-
related injuries, and assaults, including blunt and penetrating trauma, can produce
laryngeal stenosis.
Anterior blunt trauma, as sustained in motor vehicle accidents or sports-related injuries,
usually leads to posterior supraglottic and glottic stenosis. An external force at the
hypopharyngeal level may cause scar formation between the epiglottis and posterior
pharyngeal wall. Fracture of the hyoid bone displaces soft tissues posteriorly, narrowing
the laryngeal inlet. These injuries may also cause web formation on the posterior
hypopharyngeal wall and stenosis in the postcricoid area. Blunt and penetrating trauma
may lead to laceration or hematoma formation in the glottis, which will produce laryngeal
stenosis if not treated appropriately.
Systemic Diseases
Laryngeal stenosis due to fixation of the cricoarytenoid joint may be caused by
rheumatoid arthritis or juvenile rheumatoid arthritis (Still disease). About 25% of patients
with rheumatoid arthritis present with limitation of the motion of the cricoarytenoid joint.
Lupus erythematosus and gout may also cause arthritis of this joint, leading to narrowing
of the laryngeal inlet. Hoarseness, stridor, dyspnea, and pain are the signs and symptoms
of arthritic involvement. Erythematous edema of the arytenoid with the vocal cord fixed
in the paramedian or intermediate position may be found during examination. Diagnosis
must include direct laryngoscopy with palpation of the arytenoid to differentiate this from
vocal cord paralysis. Appropriate laboratory studies include erythrocyte sedimentation
rate, C-reactive protein, antinuclear antibodies, and rheumatoid factor.
Thermal Injuries
Thermal injuries of the glottis and subglottis may occur without thermal injury to the
trachea and lung due to the cooling of air by the upper airway and reflex closure of the
cords. Thermal injuries from steam, possessing 4,000 times the heat-carrying capacity of
heated air or gas, may cause significant laryngeal burns. Laser airway fires may be
particularly damaging. The pathophysiology of stenosis in laryngeal thermal injuries is
thought to be governed by three factors: direct thermal injury, toxic effects of combustion
products, and prolonged intubation (16).
Caustic Ingestions
The results of caustic ingestions on oropharyngeal and esophageal mucosa are
extensively reviewed in the literature, and laryngeal stenosis is rare. Supraglottic edema
and airway obstruction requiring tracheotomy may occur. Both acidic and alkaline
ingestions cause these effects. Severe caustic ingestions may lead to fibrosis of the
posterior cricoarytenoid muscle. Hypopharyngeal and supraglottic mucosal injury may
cause supraglottic scarring and stenosis.
Gastric Acid Reflux
Gastric acid reflux has long been thought to be an exacerbating factor in subglottic
stenosis. Subglottic stenosis in canines developed after gastric acid was placed on
preexisting mucosal abrasions. The addition of gastric acid to these lesions led to
perichondritis, chondritis, and subsequent stenosis. Only 5% to 10% of the control
animals with mucosal lesions without application of gastric acid had stenosis. The
severity of stenosis is reduced by H
2
-blocker therapy (17). Gastroesophageal reflux is
common in children and disproportionately prevalent in children with subglottic stenosis.
Although the appearance of the larynx and subglottis may strongly suggest reflux disease,
with edema, erythema, and mucosal cobblestoning, there is no completely reliable test to
confirm gastroesophageal reflux. Similarly, gross reflux may occur with no obvious
clinical signs on endoscopy. Currently, clinical judgment should balance the results from
rigid laryngoscopy, esophagogastroduodenoscopy, esophageal biopsy, and dual-port pH
probe results. In a preoperative setting, significant reflux should be treated with H
2

blockers, proton pump inhibitors, or fundoplication before any reconstructive efforts.
Radiation Effects
The effects of radiation on the adult pharynx and larynx are well established, particularly
in the context of management of laryngeal malignancy (18). Although radiation therapy
in curative doses in children is rarely required, the consequences may be similar or worse
than seen in adults. Pharyngeal or laryngeal edema and stenosis may result, often with
associated aspiration. Reconstructive surgery in these children is fraught with problems.
DIFFERENTIAL DIAGNOSIS
The differential diagnosis in laryngeal stenosis in children and adults must include all
conditions that may cause stridor, dyspnea, and respiratory distress. For patients who do
not present with acute respiratory distress, careful history taking can help the clinician
localize the site of pathology. Because the presentation of laryngeal stenosis may vary
from asymptomatic congenital subglottic stenosis in the infant to acute airway
obstruction with supraglottic injury in the adult, the differential diagnosis is quite
extensive. Table 73.4 outlines the major causes of stridor and respiratory distress that
should be considered in the differential diagnosis of laryngeal stenosis in children and
adults. Endoscopic examination with or without a biopsy provides the best chance for
definitive diagnosis.

TABLE 73.4. COMMON CONDITIONS THAT
MIMIC LARYNGEAL STENOSIS



MANAGEMENT
Natural History
Severe congenital laryngeal stenosis requires immediate airway intervention, but fewer
than half of patients with congenital laryngeal stenosis require tracheotomy, and they
may present only after repeated episodes of childhood laryngotracheal infections or later
with exercise intolerance. A patient with acquired laryngeal stenosis, produced by
internal or external trauma, infectious processes, or iatrogenic causes, has a more severe
form of stenosis that is more likely to require surgical reconstruction or a tracheotomy.
Medical Therapy
Treatment of laryngeal stenosis must include prevention. In children, this consists of
precise airway management, appropriate management of patients who require prolonged
intubation (i.e., sedation, paralysis), intubation by experienced personnel, and careful
instrumentation for diagnostic or therapeutic endoscopy. In adults, careful management
of mucosal injuries after trauma or surgical resection reduces the chance of laryngeal
stenosis. Efficient and appropriate management of infectious or inflammatory disorders,
thermal or chemical injury, and gastroesophageal reflux can diminish the chance of
iatrogenic stenosis. Medical treatment often consists of supportive therapy, including
humidification, antibiotics, or steroid therapy in a monitored and closely supervised
setting if temporary airway compromise is anticipated. Management of gastroesophageal
reflux disease may occasionally lessen the degree of subglottic stenosis without having to
resort to surgery. Similarly, treatment of the underlying disorder in autoimmune
subglottic stenosis may allow nonsurgical resolution of the disease.
Preoperative Assessment
If laryngeal stenosis is of a magnitude to warrant surgical reconstruction, the potential
outcome of surgery should be optimized. Adequate assessment and treatment of
gastroesophageal reflux is prudent preoperatively despite the lack of definitive proof that
reflux influences the outcome of surgery. Antireflux medication should be continued 3
months postoperatively.
Although the most common cause of an active larynx is reflux disease, a proportion of
children will have an active larynx without reflux disease. This may be associated with an
allergic process, an autoimmune process, or may defy explanation. It is better to repair
the larynx after resolution of inflammation, though this may take months or years in some
cases.
An adequate pulmonology workup is required in many children, especially those with a
history of bronchopulmonary dysplasia and an oxygen requirement. Oxygen requirements
over 1 L/min may make removal of a tracheotomy tube inopportune.
Some children will have a history of aspiration or will have a potential for aspiration after
reconstruction that is disguised by a severe stenosis. Turning a child into an aspirator
after airway reconstruction should be avoided if at all possible. Functional endoscopic
evaluation of swallowing and videofluroscopy (or modified barium swallow) may give
valuable information regarding a child's potential to aspirate. If there is a high risk of
aspiration, it is better to delay any reconstructive efforts.
Surgical Treatment
Surgical therapy in laryngeal stenosis begins with securing an airway and endoscopic
evaluation for diagnosis. Endoscopic management of laryngeal stenosis is successful in
most cases involving grade I or II stenosis if there are not factors predisposing to failure
(Table 73.5). Endoscopic techniques include dilatation, division or micro-trapdoor flap,
endoscopic resection with or without stenting, and carbon dioxide laser excision (19). It
is important to understand that most grade I and many grade II lesions will not require
any surgical management.

TABLE 73.5. FACTORS PREDISPOSING TO
FAILURE IN TREATING SUBGLOTTIC
STENOSIS WITH A CO
2
LASER



Endoscopic laser management of laryngeal stenosis has had success rates between 66%
and 80% (20). Careful patient selection is necessary for successful treatment. The factors
listed in Table 73.5 usually lead to failure in endoscopic management. Many grade I and
grade II stenoses will be amenable to endoscopic techniques, whereas grades III and IV
stenoses require some form of open surgical procedure. Advantages of successful
endoscopic management include precise surgical excision, low morbidity in the
procedure, minimal damage to underlying or surrounding tissues, and the ability to vary
the amount of energy delivered (21). Endoscopic management of laryngeal stenosis
allows a successful outcome without a tracheotomy. Endoscopic laser techniques that use
high energy over prolonged periods and damage underlying cartilage may create or
worsen stenosis. Because of bacterial colonization of the aerodigestive tract, prophylactic
antibiotic therapy is recommended.
If endoscopic management is unsuccessful or there are factors predisposing endoscopy to
failure, a wide variety of open surgical techniques are available for managing laryngeal
stenosis. These stenoses usually are advanced acquired stenoses. Endoscopic diagnosis is
imperative in selecting the appropriate surgical technique. The status of vocal cord
mobility, involvement of the posterior commissure, and complete evaluation of the upper
and lower airway are essential to the assessment.
The goal of open surgery for correcting laryngeal stenosis is to maintain voice function
and permit early decannulation. Contraindications to open reconstructive surgery are a
relative contraindication to general anesthetic, the continued need for tracheotomy (even
if successful), or significant gastroesophageal reflux (22). None of these are absolute
contraindications.
The evolution in open surgical management of laryngeal stenosis began in adults with
dissection of the cricoid cartilage to aid in dilatation or to open the airway, which was
subsequently stented (i.e., Rethi procedure) (23). Much of the subsequent work on
laryngeal stenosis was performed in children because a growing patient population was
created by the prolonged intubation of neonates. In 1971, Grahne (24) published a
modification of the Rethi procedure. In 1972, Fearon and Cotton (25) introduced a new
procedure developed in primates that successfully corrected subglottic stenosis in
pediatric patients using grafts to increase the airway lumen.
Open surgical techniques for reconstruction of the airway compromised by laryngeal
stenosis are usually considered in patients who are tracheotomy dependent and in patients
who are not tracheotomied but who have significant exercise intolerance or sleep
disturbance.
Otolaryngologists should have several open surgical techniques in their armamentarium
to enable successful management of a variety of pathologic conditions (Table 73.6). It is
in a patient's best interest that their airway surgery is individualized to their specific
needs, because no single procedure can adequately deal with all manifestations of
laryngeal stenosis.

TABLE 73.6. TREATMENT LARYNGEAL
STENOSIS



Anterior Cricoid Split
The anterior cricoid split procedure can be used instead of tracheotomy in the neonate
who has failed extubation (Fig. 73.1). Table 73.7 outlines suggested criteria for this
procedure. It is important to eliminate other causes of airway obstruction, such as
laryngomalacia, tracheomalacia, choanal atresia, and retrognathia. Management in this
age group requires careful endoscopic examination and management of reversible
conditions (e.g., subglottic edema, laryngeal granulations) by intubation, steroid therapy,
or laser excision (21). More severe laryngeal injury, especially with extensive mucosal
injury, may be treated with an anterior cricoid split, allowing extubation without
tracheotomy (26). Because the level of the anterior commissure in the infant lies at the
junction of the upper two thirds and lower one third of the thyroid cartilage, the anterior
laryngofissure should only extend to the lower one third of the thyroid cartilage. The
infant requires intubation for 10 days after the split, though this time period may be
reduced if an auricular or thyroid alar cartilage cap is placed over the split site.

FIGURE 73.1. Anterior cricoid split. A: Skin incision
(cricoid level). B: Vertical incision through the upper two
tracheal rings, cricoid, and lower thyroid cartilage. C:
Stay sutures. D: Loose skin closure with drain.



TABLE 73.7. CRITERIA FOR PERFORMING AN
ANTERIOR CRICOID SPLIT PROCEDURE



Laryngotracheal Reconstruction
Anterior Cartilage Graft
For grade I or II subglottic stenosis, an anterior autogenous costal cartilage graft is a
highly effective method for reconstruction of the airway (27) (Fig. 73.2). This may also
be effective in selected grade III lesions. A boat-shaped flanged graft is placed between
the divided anterior lamina of the cricoid cartilage and if required may extend inferiorly
across two or three tracheal rings. It should not transgress the anterior commissure. Other
options for graft material include thyroid alar and auricular cartilage, though neither has
the same structural intergrity as costal cartilage (28).

FIGURE 73.2. Anterior laryngofissure with anterior
augmentation. A: Vertical incision (inferior to the cords)
through the thyroid cartilage, cricoid, and upper tracheal
rings. B: Beveled and elliptical cartilage graft. C:
Cartilage graft in place with Prolene sutures.



Posterior Cartilage Graft
Posterior glottic stenosis is a common sequelae of prolonged intubation and is often
misdiagnosed as bilateral cord paralysis. There may be associated fibrosis or ankylosis of
the cricoarytenoid joints. A posterior costal cartilage graft placed after division of the
posterior cricoid lamina may be performed as a single- or two-stage procedure. A narrow
graft (less than 6 mm) is usually adequate, and overaugmentation risks aspiration. The
same technique is used for grade II or III subglottic stenosis with primarily posterior
cricoid scarring. In children younger than 7 to 8 years, it is usually necessary to perform a
complete anterior laryngofissure to adequately access the posterior glottis. Particular care
should be taken to both accurately divide and reconstruct the anterior commissure during
a complete laryngofissure, to ensure perfect cord alignment and to minimize the risk of
long-term vocal dysfunction.
Anterior and Posterior Cartilage Graft
Grades III and IV subglottic stenoses usually require anterior and posterior costal
cartilage grafting. After placement of the posterior cartilage graft, the anterior airway can
then be closed over an appropriately sized endotracheal tube to estimate the size of the
anterior graft required. If the anterior cricoid can be closed without tension, then an
anterior graft may not be required. A variation of this procedure is an anterior graft with a
posterior split of the cricoid lamina. This option is usually limited to younger children.
Grade IV subglottic stenosis will usually require more than one procedure to achieve
decannulation.
Cricotracheal Resection
An alternative to anterior/posterior cartilage grafting is cricotracheal resection (29,30)
(Fig. 73.3). The concept is the removal of the diseased portion of the airway, with the
introduction of healthy tissue into the subglottis. This is a more technically challenging
procedure than anterior/posterior cartilage grafting and is therefore usually reserved for
severe (grade III or IV) subglottic stenosis. It also has particular application in the
reconstruction of the airway that has failed previous laryngotracheal reconstruction.
There is a higher chance of achieving decannulation after a single procedure with
cricotracheal resection than standard cartilage augmentation laryngotracheal
reconstruction. The advantages of the procedure include glottic sparing, avoidance of
donor site morbidity, and a near normal-appearing and mucosalized airway.
Disadvantages include a risk to the recurrent laryngeal nerves and anastomotic
dehiscence. Patient selection is important, and subglottic scarring within 3 mm of the
vocal cords is a relative contraindication.

FIGURE 73.3. Cricotracheal resection. A: Stenotic
segment for resection. B: Anterior cricoid split. C:
Excision anterior cricoid lamina. D: Elevation of trachea
off esophagus. E: Stenotic upper trachea for sacrifice. F:
Removal stenotic upper trachea. G: Telescoping trachea
into posterior cricoid lamina. H: Thyrotracheal
anastomosis.



Stenting Options
The primary decision that needs to be made in terms of stenting is the required duration
of stenting. The more unstable the airway reconstruction (e.g., after an anterior/posterior
graft) or a history of previous failed reconstruction would suggest a longer period of
stenting is prudent. Long-term stenting may be achieved with a T-tube (Montgomery or
Hood) or a wired-in metal tracheotomy tube within a Teflon stent (Aboulker or Cotton
Lorenz) (Fig. 73.4). Generally, in children under 4 years of age T-tubes are best avoided
because T-tubes with less than an 8 mm outer diameter carry a higher risk of mucus
occluding the lumen of the tube. Shorter term stenting may be adequately achieved with a
suprastomal Teflon stent, but these should ideally be removed after several weeks to
prevent stenosis occurring between the distal end of the stent and the tracheotomy tube.

FIGURE 73.4. Anterior laryngofissure with posterior
cricoid lamina split. A: Vertical midline laryngofissure
from the thyroid notch to the proximal trachea or stoma.
B: Division of posterior cricoid. C: Holinger metal
tracheotomy tube wired to Aboulker or Cotton stent. D:
Stent and tracheotomy tube in place. E: Stent and
tracheotomy tube in place with an anterior costal cartilage
graft.



If the period of stenting is under 2 weeks and lung function is adequate, consideration
may be given to a single-stage procedure, using an endotracheal tube as a stent. This
technique is highly dependent on access to a first-class intensive care unit. Paralysis is
best avoided to allow the child some opportunity to maintain their own airway in the
event of an accidental extubation. Most children under the age of 3 will require sedation,
and many children over 3 will not. The period of intubation depends on the surgery
performed, and may vary from a day for selected anterior cartilage grafts to 14 days for
an anterior/posterior cartilage graft.
In some circumstances, no stent may be required for a two-stage reconstruction. An
anterior costal cartilage graft laryngotracheal reconstruction rarely needs a stent, and
selected cricotracheal resections may not need a stent.
DECISION MAKING
Before deciding on an open surgical reconstructive technique, conservative endoscopic
treatment of laryngeal stenosis should be considered. This approach may include
endoscopic dilatation, laser therapy, tissue removal by endoscopic microsurgical
techniques, local and systemic steroid therapy, and antibiotic therapy. If these techniques
are unsuccessful, open reconstruction of the airway can be considered.
Several unique features must be considered in treating children. The patient with acquired
laryngeal stenosis due to long-term intubation frequently has underlying chronic
pulmonary disease. Lung disease, such as bronchopulmonary dysplasia, must be
addressed medically before surgical correction of the airway. In many children with
laryngeal stenosis, other congenital or acquired anomalies require surgical repair.
Reconstruction of the airway can be delayed until the other surgical procedures are
completed because the existing tracheotomy tube allows easy and safe access to the
airway.
In adults and children, any indication of significant gastroesophageal reflux should
undergo correction by medical means (e.g., H
2
blockers, antacids) or surgical methods
(e.g., Nissen fundoplication) before reconstruction of the airway. If gastroesophageal
reflux is not successfully treated before reconstruction, the reconstructed airway may
suffer repeated injury by acidic gastric contents, causing granulation tissue and further
stenosis.
The variety of open surgical procedures available for reconstruction, including some that
are not outlined here, allows the otolaryngologist to manage the stenotic larynx regardless
of etiologic factors. Severe stenosis frequently requires more than one surgical correction
for successful reconstruction. Therefore, early stenotic lesions should be treated
aggressively to maintain some of the airway.
COMPLICATIONS
Complications related to airway reconstruction may occur intraoperatively, early
postoperatively, or late postoperatively. Intraoperative complications include hypoxia,
pneumothorax (usually related to harvesting rib cartilage), and pneumomediastinum.
Similar problems may occur postoperatively, as may wound infections, graft
displacement, stent dislodgement, aspiration, and mucus plugging of the tracheotomy
tube. Single-stage reconstruction carries particular risks, including endotracheal tube
obstruction, unplanned extubation, glottic edema, and narcotic withdrawal.
All patients who are discharged with tracheotomy tubes should be taught tracheotomy
care and given spare tracheotomy tubes, including one a size smaller than resides in the
patient in case of difficulty with re-insertion in an emergency. The family should be
instructed in tracheotomy care, including suctioning and changing the tracheotomy tube.
EMERGENCIES
Emergent complications in the care of laryngeal stenosis include airway obstruction,
aspiration of a wire or stent, hemorrhage or hematoma formation, and pneumothorax with
resulting respiratory distress.
Airway obstruction may be caused by mucous plugs or granulation tissue. Humidified air
should be provided, and changing of the inner cannula or tracheotomy tube should be
performed regularly to prevent plugging. Mucous plugs should be carefully suctioned.
Granulation tissue may be treated with aerosolized or systemic steroids (e.g.,
dexamethasone, 0.5 mg/kg/day to a maximum of 20 mg/day) by mouth or through the
tracheotomy tube, depending on the site of granulation tissue. If granulation tissue is
exuberant, the patient may need to be admitted and closely monitored during therapy.
Solitary pedunculated granulomas may be safely removed with forceps during removal of
the stent or during an interval examination postoperatively. These patients should be
placed on a weaning dose of steroids.
To avoid some of these complications, the surgical technique should include use of drains
and, in open airway procedures, closure of the skin that allows the escape of air. A
radiograph of the chest should always be obtained postoperatively for open reconstructive
procedures. If an anterior costal cartilage graft is harvested, sterile saline should be
placed in the chest wound and a positive pressure breath given to determine the
possibility of an air leak. Good surgical technique with careful hemostasis and education
of ancillary personnel and family can prevent these emergencies (Table 73.8).

TABLE 73.8. EMERGENCIES SURGICAL
TREATMENT OF LARYNGEAL STENOSIS




HIGHLIGHTS
The narrowest part of the airway in the pediatric patient is the
subglottis; in the adult, it is the glottis.
Symptoms of obstruction differ by location. Supraglottic
stenosis presents with inspiratory stridor, glottic and subglottic
stenoses with biphasic stridor, and lower airway obstruction
with expiratory stridor.
Endoscopy is necessary for diagnosing laryngeal stenosis,
although lateral and anteroposterior neck radiographs,
computed tomography, and fluoroscopy may also contribute
information.
Acquired laryngeal stenosis is much more common than
congenital stenosis, and it is usually a more difficult process to
repair.
The most important method of preventing acquired laryngeal
stenosis is proper and experienced airway instrumentation and
prompt medical treatment of infections or inflammatory
disorders.
Dilatation is usually not successful for long-term management
of fixed or firm stenosis.
Successful repair of laryngeal stenosis requires careful
evaluation of the entire airway, including the nasopharynx,
supraglottis, trachea, and lung parenchyma.
Severe stenosis may require more than one procedure for
successful repair.
Gastroesophageal reflux must be controlled before surgical
repair of laryngeal stenosis.
Measurement of airway by endotracheal tubes is a reliable and
objective method in the diagnosis and follow-up of laryngeal
stenosis
CHAPTER REFERENCES
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Laryngoscope 1979;89:866877.
2. Walander A. The mechanism of origin of congenital malformation of the larynx. Acta Otolaryngol
1955;45:426432.
3. Holinger PH, Kutnick SL, Schild JA. Subglottic stenosis in infants and children. Ann Otol Rhinol
Laryngol 1976;85:591599.
4. Cohen SR, Isaacs H. Otolaryngological manifestations of arthrogryposis multiplex congenita. Ann
Otol Rhinol Laryngol 1976;85:484490.
5. McDonald IH, Stocks JG. Prolonged nasotracheal intubation. Br J Anaesth 1965;37:161173.
6. Quiney RE, Gould SJ. Subglottic stenosis: a clinicopathologic study. Clin Otolaryngol
1985;10:315327.
7. Papsidero MJ, Pashley NR. Acquired stenosis of the upper airway in neonates. Ann Otol Rhinol
Laryngol 1980;89:512514.
8. Ratner I, Whitfield J. Acquired subglottic stenosis in the very low-birth-weight infant. Am J Dis
Child 1983;137:4043.
9. Sasaki CT, Horivchi M, Koss N. Tracheotomy-related subglottic stenosis: bacteriologic
pathogenesis. Laryngoscope 1979;6:857865.
10. Jackson C. High tracheotomy and other errors as the chief causes of chronic laryngeal stenosis.
Surg Gynecol Obstet 1921;32:392398.
11. Brantigan CO, Grow JB Sr. Cricothyroidotomy: elective use in respiratory problems requiring
tracheotomy. J Thorac Cardiovasc Surg 1976;71:7281.
12. Boyd AD, Romita MC, Conlan AA, et al. A clinical evaluation of cricothyroidotomy. Surg
Gynecol Obstet 1979;149:365368.
13. Sise MJ, Shacksord SR, Crickshank JC, et al. Cricothyroidotomy for long-term tracheal access.
Ann Surg 1984;200:713.
14. McGill J, Clinton JE, Ruiz E. Cricothyroidotomy in the emergency department. Ann Emerg Med
1982;11:361364.
15. Esses BA, Jafek BW. Cricothyroidotomy: a decade of experience in Denver. Ann Otol Rhinol
Laryngol 1987;96:519524.
16. Flexon PB, Cheney ML, Montgomery WW, et al. Management of patients with glottic and
subglottic stenosis resulting from thermal burns. Ann Otol Rhinol Laryngol 1989;98:2730.
17. Little FB, Koofman JA, Kohut RI, et al. Effect of gastric acid on the pathogenesis of subglottic
stenosis. Ann Otol Rhinol Laryngol 1985;94:516519.
18. Calcaterra TC, Stern FS, Ward PH. Dilemma of delayed radiation injury of the larynx. Ann Otol
1972;81:501507.
19. Dedo HH, Sooy CD. Endoscopic laser repair of posterior glottic, subglottic and tracheal stenosis
by division or micro-trapdoor flap. Laryngoscope 1984;94:445450.
20. Simpson GT, Strong MS, Healy GB, et al. Predictive factors of success or failure in the
endoscopic management of laryngeal and tracheal stenosis. Ann Otol Rhinol Laryngol
1982;91:384388.
21. Holinger LD. Treatment of severe subglottic stenosis without tracheotomya preliminary report.
Ann Otol Rhinol Laryngol 1982;91:407412.
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CD, Stool SE, eds. Pediatric otolaryngology, 2nd ed. Philadelphia: W.B. Saunders, 1990:1194.
23. Rethi A. An operation for cicatricial stenosis of the larynx. J Laryngol Otol 1956;70:283293.
24. Grahne B. Operative treatment of severe chronic traumatic laryngeal stenosis in infants up to three
years old. Acta Otolaryngol 1971;72:134137.
25. Fearon B, Cotton RT. Surgical correction of subglottic stenosis of the larynx. Ann Otol Rhinol
Laryngol 1972;81:508513.
26. Cotton RT, Seid AB. Management of the extubation problem in the premature child. Ann Otol
Rhinol Laryngol 1980;89:508511.
27. Cotton RT, Gray SD, Miller RP. Update of the Cincinnati experience in pediatric laryngotracheal
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

74 STRIDOR, ASPIRATION, AND COUGH
Head & Neck SurgeryOtolaryngology
74




STRIDOR, ASPIRATION, AND COUGH
MARK E. GERBER
MICHAEL E. DUNHAM
LAUREN D. HOLINGER

M.E. Gerber, M. E. Dunham, and L.D. Holinger: Department of Pediatric Otolaryngology, Children's
Memorial Hospital, Chicago, Illinois.


Anatomy, Physiology, and Pathophysiology
Stridor
Cough
Swallowing
Stridor
Evaluation
Differential Diagnosis of Pediatric Stridor
General Principles of Airway Management
Complications
Aspiration
Evaluation and Diagnosis
Evaluation: Radiography and Special Diagnostic Studies
Management
Alimentary Procedures
Laryngeal Incompetence Procedures
Cough
Evaluation
Differential Diagnosis
Management
Chapter References
ANATOMY, PHYSIOLOGY, AND PATHOPHYSIOLOGY
The complex structures of the upper airway allow for the coordination of both respiration
and swallowing. The structural and physiologic relationships between the various
structures change with growth from infancy through adulthood. The infant larynx is
initially located high in the neck, bringing the tip of the epiglottis behind the soft palate.
The pharyngeal structures are closer together than in the adult, and the hyoid bone is
higher. This position creates a separation of the airway from the digestive tract. The air
movement is predominantly transnasal, whereas swallowing occurs through the lateral
channels around the epiglottis, into the pyriform recesses and the cricopharyngeal inlet.
With growth, the larynx descends, separating from the soft palate and creating a larger
pharynx that enhances speech production. However, descent also creates a common
passageway for both food and air, increasing the possibility for food, foreign bodies, or
gastric contents to enter the airway.
Stridor
The signs and symptoms of a child with respiratory distress are usually different
depending on the location and severity of obstruction (Table 74.1) (1). It is essential to
assess and localize the potential site and cause of the obstruction. Airway obstruction at
the level of the nasopharynx or oropharynx produces the inspiratory low-pitched sound
called stertor or snoring and is discussed elsewhere in this section. Dynamic supraglottic
and glottic obstructions tend to produce inspiratory stridor due to collapse of these
structures with negative inspiratory pressure. Intrathoracic airway lesions cause
expiratory obstruction. Stridor caused by fixed subglottic laryngeal and cervical tracheal
lesions is most often biphasic.

TABLE 74.1. SIGNS AND SYMPTOMS OF
AIRWAY OBSTRUCTION BY LOCATION



The infant larynx and trachea are much smaller than those of the adult. In the infant, the
vocal cords are 6 to 8 mm long and the vocal processes of the arytenoids extend one half
the length. The posterior glottis has a transverse length of 4 mm. The subglottis has a
diameter of 5 to 7 mm. The trachea is 4 cm long and has a diameter of 3.6 mm. The ratio
of cartilaginous to membranous trachea is 4.5:1.
Stridor is the audible noise produced by turbulent airflow through a partially obstructed
airway. Obstructing lesions of the airways produce the turbulent airflow. With narrower
columns of air, small partial obstructions are more likely to cause significant turbulence.
This is why the infant with an upper respiratory tract infection may exhibit the signs of
stridor and croup. In other words, the normal infant glottis (approximate cross-sectional
area of 14 mm
2
) is narrowed by 35% due to 1 mm of edema (Fig. 74.1). The smallest part
of the normal larynx, the subglottis (28.3 mm
2
cross-sectional area), is narrowed by 44%
due to 1 mm of edema (Fig. 74.2). In contrast, an adult larynx has a much larger cross-
sectional area and is therefore minimally narrowed by the same 1 mm of edema (2).

FIGURE 74.1. The triangular aperture of the normal
infant larynx is approximately 7 4 mm, an area of 14
mm
2
. When intubation or an upper respiratory tract
infection causes 1 mm of edema, the cross-sectional area
is reduced to 5 mm
2
, only 35% of normal. (From
Holinger LD. Evaluation of stridor and wheezing. In:
Holinger LD, Lusk RP, Green CG, eds. Pediatric
laryngology and bronchoesophagology. Philadelphia:
Lippincott-Raven, 1997:4148, with permission.)



FIGURE 74.2. The normal newborn subglottic larynx
has a diameter of 5 to 7 mm and a cross-sectional area of
approximately 28.3 mm
2
. Only 1 mm of edema reduces
the area to 12.6 mm
2
, 44% of normal. (From Holinger
LD. Evaluation of stridor and wheezing. In: Holinger LD,
Lusk RP, Green CG, eds. Pediatric laryngology and
bronchoesophagology. Philadelphia: Lippincott-Raven,
1997:4148, with permission.)



Cough
Cough is a complex reflex that is initiated by sensory receptors in the respiratory
epithelium. Receptors are concentrated in the larynx and carina and at other airway
bifurcations. There are no receptors beyond the terminal bronchioles. Other receptors are
in the nose, nasopharynx, external auditory canal, tympanic membrane, stomach, pleura,
pericardium, and diaphragm. Afferent pathways in the tenth and, to a lesser extent, the
fifth and ninth cranial nerves carry impulses to the cough center in the medulla. Cough
can also voluntarily be initiated without stimulation from other afferent pathways. The
efferent fibers of the cough reflex carry their signals from the cough center to the
diaphragm and intercostal muscles through the phrenic and spinal motor nerves,
respectively. The abdominal and pelvic muscles also participate in the efferent limb.
The mechanics of a cough involve developing and then sustaining a high velocity column
of air. To do this, the cough begins with an initial inspiratory phase in which there is
maximum abduction of the vocal cords and an increase in the chest dimensions, filling
the lungs with air to a high volume. The second phase follows with rapid closure of the
larynx at the supraglottic and glottic levels. Expiratory muscle contraction forces a rise in
airway pressure during this compressive phase of coughing. It is the closure of the
ventricular bands (false focal folds) that contributes the greatest sphincteric effect in
preventing the flow of air during the compressive phase. The third (expiratory) phase
occurs as the glottis suddenly opens and rapid airflow expectorates mucus and foreign
material. Maintenance of airflow velocity is assisted during expiration by continued
narrowing of the opened supraglottic larynx. Vibrations of the laryngeal mucosa also
assist in secretion clearance during the expiratory phase.
Swallowing
Traditionally, the normal swallow is divided into four stages: preparatory, oral,
pharyngeal, and esophageal. The first two are under voluntary control except in the
newborn period, when the swallowing reflex is regulated at the level of the brainstem.
The second two are reflex actions. The afferent limb consists of sensory and
proprioceptive fibers in the glossopharyngeal, trigeminal, and superior laryngeal nerves
that supply the laryngeal and pharyngeal mucosa. Impulses are transmitted to the
swallowing center in the floor of the fourth ventricle. The efferent limb consists of
general visceral efferent fibers that begin in the nucleus ambiguous and descend through
the vagus nerve to supply the laryngeal and pharyngeal musculature (Fig. 74.3).

FIGURE 74.3. Glottic closure reflex.



In the preparatory phase, food is taken in and prepared into a bolus held between the hard
palate and central anterior two thirds of the tongue. The apposition of the base of tongue
and soft palate prevents food from traveling posterior while chewing. During the oral
phase, the anterior tongue elevates and contacts the hard palate, the soft palate closes off
the nasopharynx, and the food bolus is pushed into the pharynx. Squeezing liquid from
the nipple appears to be part of an infant's oral phase. The pharyngeal phase begins as the
bolus passes the tonsillar pillars. The palatopharyngeal partition, made up of the apposing
pharyngeal constrictors, palate, and palatopharyngeus, directs the food into the
hypopharynx, and the pharynx and larynx elevate. At the onset of the esophageal phase,
respiration stops, the glottis closes, the nasopharynx is occluded by the velum, the
cricopharyngeus relaxes, and esophageal peristalsis begins.
The swallowing reflex in children varies in several ways from that of adults and
undergoes an orderly maturation as they develop. Before the thirty-fourth week of
gestation, the premature infant demonstrates a poorly coordinated and insufficient
suckling response. Beyond the thirty-fourth week, neuromuscular maturation progresses
and oral feeding can usually be maintained, with the full-term infant able to suckle at
birth. The anatomy of the swallowing mechanism also differs from that of an adult (Fig.
74.4). As mentioned above, the hard palate is closer to the skull base and the larynx is
higher in the neck, and the adenoid pad, tonsils, and tongue are relatively larger in
children. Therefore, nasopharyngeal closure requires less angulation of the soft palate,
whereas the tonsils and tongue assist in oropharyngeal propulsion. With age, the oral
cavity and pharynx enlarge, the larynx descends in the neck, the relative size of the
tongue decreases, and teeth erupt.

FIGURE 74.4. The anatomy of the swallowing
mechanism differs between that of children and adults. A:
Child. B: Adult. (Adapted from Paustian G, Holinger LD.
Feeding, swallowing, dysphagia, and aspiration. In:
Holinger LD, Lusk RP, Green CG, eds. Pediatric
laryngology and bronchoesophagology. Philadelphia:
Lippincott-Raven, 1997:305316.)



Airway protection in the normal person is maintained by three interlocking systems. The
first system is the swallow mechanism, mentioned above. The second system is the three-
tiered system of the laryngeal sphincters: the epiglottis, aryepiglottic folds, and
arytenoids (first level); the false vocal folds (second level); and the true vocal folds (third
level). The third system is that of mucociliary clearance and the cough reflex. A
breakdown in any of these systems can result in aspiration.
STRIDOR
Evaluation
History and Physical Examination
The extent and urgency with which the diagnostic evaluation of a stridorous patient is
carried out is determined by the patient's degree of distress. Assessment begins with a
careful history, emphasizing the birth history, the age of stridor onset, severity,
progression, and fluctuation of respiratory symptoms. Posturing and position changes that
either improve or worsen respiratory distress are also noted in addition to related
symptoms, including hoarseness, eating or feeding difficulties, and sleep-disordered
breathing. The mnemonic SPECS-R can be used to organize the history (Table 74.2) (2).

TABLE 74.2. STRIDOR: PERTINENT HISTORY
MNEMONIC



The initial physical examination assesses the severity of respiratory distress and the need
for emergency airway management. Patients with severe respiratory distress, particularly
children, require careful noninvasive inspection to avoid exacerbating airway
compromise. Respiratory rate and level of consciousness are the most important
indicators of severity. Tachypnea is often the first sign of respiratory distress in children.
Relatively quiet shallow breathing characterizes late respiratory failure and exhaustion; a
mental status assessment at this stage reveals confusion or lethargy and suggests
impending respiratory arrest. Increased work of breathing with suprasternal, subcostal,
and intercostal retractions in the stridorous patient indicates significant airway
obstruction but does not necessarily preclude a thorough diagnostic workup before
airway intervention. Auscultation is done by not only listening over the lung fields but
also along the neck, mouth, and nose. This process assists in defining the respiratory
phase (inspiratory, expiratory, biphasic) during which stridor occurs and the stridor
intensity, pitch, and quality.
When a neonate presents with complete or severe obstruction, the child is immediately
suctioned, an oral airway placed, and mask ventilation attempted. If the obstruction
persists, a laryngoscope is used to visualize the larynx. If it appears patent, a small
endotracheal tube is placed into the trachea. If the ventilatory status does not improve, the
etiology is in the lower airway, lungs, or pleural cavity and further investigations ensue.
Cyanosis is a late and inconsistent sign of respiratory failure in the stridorous infant. In
the cyanotic-appearing infant without stridor or increased work of breathing, other
etiologies must be sought (Table 74.3). Cardiovascular and central nervous system causes
of cyanosis are not associated with stridor. Coughing, gagging, aspiration, pneumonia,
and reflex apnea can be prominent findings when a gastrointestinal etiology such as
gastroesophageal reflux or tracheoesophageal fistula is present. In addition to obstruction
of the airway itself, problems with the pleural cavities or the lung must also be assessed
(2).

TABLE 74.3. DIFFERENTIAL DIAGNOSIS OF
CYANOSIS IN THE NEWBORN



Once it has been determined that respiratory failure is not imminent, a more detailed
physical examination can be completed. A general examination, including weight,
percentile growth, and development, is also an important part of stridor assessment. The
nasal and oral cavities and the oropharyngeal airways are inspected for possible
inflammatory lesions, neoplasms, adenotonsillar hypertrophy, and congenital
malformations. Indirect mirror examination of the larynx can occasionally be
accomplished in older cooperative children. Most often, flexible fiberoptic airway
endoscopy in the awake patient is the best way to assess the upper airway dynamics (Fig.
74.5). In children, this must be done carefully, with resuscitation equipment available and
patient monitoring when indicated. Topical anesthesia (lidocaine 2%) with decongestion
(oxymetazoline 0.05%) is applied in children over 1 year of age. The semisitting position
is usually preferable, with adequate restraint an essential element. The flexible endoscope
can be passed through both nares to evaluate bilateral nasal and nasopharyngeal patency
and velopharyngeal function in addition to inspection of the orophyngeal,
hypopharyngeal, and laryngeal airway dynamics.

FIGURE 74.5. Awake flexible fiberoptic laryngoscopy.



Radiology and Special Studies
Radiographic imaging of the airway remains central in the evaluation of the stridorous
child. Chest and airway radiographs are used to evaluate large airway caliber and the lung
parenchyma. To obtain optimal plain films in a pediatric patient, radiology technician
expertise and the use of specially designed restraining devices for positioning the child in
an upright neutral position are essential. High-kilovoltage, filtered, and magnified
radiographs are usually obtained in both the anteroposterior and lateral projections. When
there is suspicion of foreign body, low-kilovoltage films should be done to enhance
visualization of objects that are only slightly radiopaque. Inspiratory and expiratory films
or lateral decubitus films can also supplement posteroanterior and lateral chest
radiographs in evaluating suspected radiolucent foreign bodies. Changing airway
dynamics can alter plain radiographic images. Frequently, films need to be repeated to
clarify findings. Fluoroscopy can also be used to clarify findings and to further assess
dynamic function. Fluoroscopy during sedation-induced sleep can be helpful in complex
children with sleep-disordered breathing that may be due to obstruction at one or more
anatomic sites (3).
Specialized radiographic techniques are used to evaluate stridor in appropriate
circumstances. The barium esophagram is useful for evaluating stridor due to suspected
vascular rings and tracheoesophageal fistulae. Computed tomography with contrast is
currently the most useful technique for confirming suspected choanal atresia or stenosis
and evaluating most vascular compression syndromes and mass lesions affecting the
airway.
There is no gold standard for identification of extraesophageal reflux in children, and the
actual incidence and clinical implications remains controversial. Normative data have not
been collected for extraesophageal reflux in either adults or children. Although dual pH
probe monitoring is currently the best method available for assessment of acid reflux to
the lower or upper esophagus, the definition of significant reflux to the pharynx has not
yet been determined. Some indicate that any reflux to the level of the pharynx is
pathologic and should be treated (4).
Laryngeal findings thought to show significant gastropharyngeal reflux have been
catalogued (5). Posterior glottic edema, hypervascularity, and pseudosulcus are
considered important signs of reflux laryngitis. These laryngeal signs may be present
even when gastroesophageal reflux cannot be demonstrated by pH probe. These findings
have been shown to be reversible, however, through empiric reflux therapy (6).
Histologic evidence of inflammation in biopsy specimens of esophageal mucosa provides
indirect evidence of gastroesophageal reflux disease (GERD). Pertinent findings include
intraepithelial eosinophilia, thickened basal layer, and increased papillary height. These
findings have also been shown to occur within the larynx (5,7,8).
In children with diagnosed upper airway obstruction and stridor, the severity of
respiratory compromise and the need for intervention are often difficult to determine. For
example, a child who has known or suspected laryngomalacia and significantly loud
inspiratory stridor but who does not appear to be in respiratory distress could either
require airway intervention or could be expected to recover spontaneously. Apnea
detectors and continuous pulse oximetry objectively monitor respiratory function and can
be used on an outpatient basis or during a short hospitalization. Similarly, chronic
hypoxemia associated with cor pulmonale can be followed with echocardiography.
Polysomnography can be useful when trying to obtain objective evidence of sleep-
disordered breathing. Although these studies do not provide diagnostic information about
the specific site of the lesion, they can be used to assess the severity of the airway
obstruction and can help the clinician decide if further intervention is needed.
Airway Endoscopy
Direct endoscopy is indicated for undiagnosed stridor and for therapy of certain airway
lesions. The most challenging endoscopic procedures are performed for stridor in
children. The small caliber of the air passages, the complexity of the instrumentation, and
the relative physiologic instability of the young child leave little margin for error.
Because of the shared responsibility for the patient's airway, good communication
between the surgical endoscopist and anesthesiologist is imperative before initiating the
procedure. The surgeon must ensure that adequate personnel and safety equipment are
present before the procedure starts. Generally, rigid bronchoscopes with rod-lens
telescopes are used in the endoscopic assessment of a partially obstructed airway because
ventilation can be maintained through the bronchoscope sheath. Nasal and oral airways,
self-inflating bags with masks, appropriate endotracheal tubes, laryngoscopes, and a
tracheotomy set should be available for airway emergencies.
The child arrives in the operating room without prior sedation. If not already done, the
endoscopist can perform an awake flexible fiberoptic laryngoscopy to assess airway
dynamics, including vocal fold mobility. Before induction of anesthesia, all endoscopy
equipment will need to be evaluated by the endoscopist and will need to be ready for
immediate use in case of emergency. This will include an appropriately sized
laryngoscope, Hopkins rod-lens telescope, and appropriately sized bronchoscope (Table
74.4) with Hopkins rod-lens telescope and light cable, and suctions. The next one or two
smaller bronchoscope(s) should also be available but not necessarily on the working
table. The use of a camera on the telescope with video monitors and a videotape recorder
enables the other operating room team members to follow the progress and improves
teaching capabilities.

TABLE 74.4. GUIDELINES FOR SELECTION OF
APPROPRIATE BRONCHOSCOPE AND
ESOPHAGOSCOPE BY AGE



Anesthesia is usually induced via mask with halothane, which is less irritating and better
tolerated than other inhalational agents. However, other agents such as sevoflurane are
also used on occasion. An intravenous line is usually placed after the initial induction.
Regardless of the mode of induction, spontaneous ventilation is maintained as much as
possible to maximize the ability to assess complete airway dynamics below the vocal
cords. Topical lidocaine (1% for children under 10 kg, 4% for larger children) is sprayed
onto the vocal cords and into the trachea for laryngotracheal anesthesia. The total dose
should be kept to less than 5.0 mg/kg. A second application can be used if the procedure
lasts longer than 15 to 30 minutes.
The child is carefully positioned with the neck extended and the occiput slightly elevated.
The endoscopist then inserts a laryngoscope to allow for visualization of the larynx. The
most common types of handheld laryngoscopes useful for this purpose include the
Jackson side slide, Parson, or an anesthesia-type handle with a Phillips blade.
Microlaryngoscopy and bronchoscopy can be performed using an insufflation technique
(Fig. 74.6) when the patient is breathing spontaneously. This technique provides excellent
visualization using the Hopkins rod-lens telescope without the ventilating bronchoscope
for magnification of the larynx, trachea, and bronchi, minimizing potential trauma.
Pharyngeal insufflation using a high-flow oxygen and halothane mixture assists in
maintaining an adequate depth of anesthesia. This can be done through the side port of
the laryngoscope when one is present or by using a suction catheter or endotracheal tube
passed transnasally into the oropharynx. In neonates and older children, spontaneous
ventilation/insufflation techniques may not always be tolerated within safe parameters. In
these cases, after the safety and security of the airway has been established, brief
paralysis can be used. The Hopkins rod-lens telescope is then sheathed within an age-
appropriate ventilating bronchoscope to maintain the airway during visualization. With
this method, bronchial secretions can be sent for laboratory studies, including
bacteriology, tuberculosis, and fungal cultures, and for evaluation of fat-laden
macrophages (for suspected aspiration), hemosiderin (for hemosiderosis), and eosinophils
(for bronchopulmonary allergy).

FIGURE 74.6. Microlaryngoscopy using insufflation
technique. (From Holinger LD. Diagnostic endoscopy of
the pediatric airway. Laryngoscope 1989;99:346, with
permission).



Sizing of the airway can be accomplished by orotracheal intubation with an endotracheal
tube that has a leak between 10 and 25 cm water pressure. The leak can be assessed
visually, using the Hopkins rod-lens telescope to see airflow or bubbling as the pressure
climbs with the anesthetic pop-off valve in the closed position. By starting out with a
smaller tube and increasing when the leak is at pressures less than 10 cm water pressure,
the development of edema from placing too large of a tube can be avoided. This method
of sizing will allow for comparison with normative data and also for longitudinal
assessment of airway growth. At the conclusion of the procedure, this lets the patient
emerge from the anesthetic with or without the endotracheal tube in place.
Postoperative care includes close monitoring in the recovery room. Keeping children in a
comfortable position, often with the head of bed elevated, minimizes airway distress.
Supplemental oxygen and humidification may be helpful until the child is fully awake.
Some degree of airway swelling is expected after endoscopy. Intravenously administered
dexamethasone, given at the usual dosage of 0.5 to 1.0 mg/kg (up to 12 mg), is often used
as a preventative measure at the beginning of the procedure to limit postoperative edema.
Racemic epinephrine treatments can also help to minimize postoperative morbidity due to
edema.
Differential Diagnosis of Pediatric Stridor
A brief review of some of the more important causes of noisy breathing in children can
be found in Table 74.5. In 85% of children under age 2.5 years presenting with stridor,
the etiology is congenital. Inflammation, trauma, or foreign bodies most often cause the
remaining cases. The age at onset is variable, and onset is usually sudden. Acquired
stridor is more likely than congenital stridor to require airway intervention. Congenital
stridor is often not present at birth but usually presents before the age of 4 months. About
half the cases are due to laryngeal anomalies. Synchronous anomalies occur in 10% to
45% of cases, underscoring the need for a thorough diagnostic workup (9).

TABLE 74.5. DIFFERENTIAL DIAGNOSIS OF
COMMON CAUSES OF NOISY BREATHING IN
CHILDREN



Laryngomalacia
Laryngomalacia is the most common cause of stridor in infancy. The symptoms often do
not present for days to weeks after birth, subsequently peak, and typically resolve by 12
to 18 months of age. The diagnosis is generally suspected on auscultation of the stridor
and confirmed by flexible nasopharyngoscopy. The stridor is usually low in pitch with a
fluttering quality and most prominent with the child in the supine position or with
agitation. Because this is a dynamic process, it is important to examine the larynx while
the child is awake and phonating. The classic finding is a cyclical collapse of the
supraglottic larynx with inspiration (Fig. 74.7 and Fig. 74.8; see also Color Plate 18 and
Color Plate 19 following p. 370).

FIGURE 74.7. Endoscopic view of laryngomalacia
during expiration. (See also Color Plate 18 following p.
370.)



FIGURE 74.8. Endoscopic view of laryngomalacia
during inspiration with folding inward of the epiglottis,
shortened aryepiglottic folds, and collapse of the
cuneiform cartilages completely obstructing the laryngeal
introitus. (See also Color Plate 19 following p. 370.)



Anatomic, neurologic, and inflammatory factors all may contribute to the development of
laryngomalacia. The most common underlying anatomic pathologies are shortening of
the aryepiglottic folds and anterior collapse of the cuneiform cartilages. Immature
neuromuscular control has also been thought to play a role. In addition, gastroesophageal
reflux is frequently associated with laryngomalacia. The increased negative intrathoracic
pressure generated on inspiration with a partially collapsed supraglottic larynx can
increase the retrograde flow of gastric contents into the esophagus. The reverse may also
occur with pharyngoesophageal reflux, inducing posterior supraglottic edema and
secondarily laryngomalacia.
Laryngomalacia rarely requires surgical intervention. However, a few patients will have
symptoms such as inability to feed orally, cor pulmonale, failure to thrive, or life-
threatening episodes of airway obstruction. Before the 1980s, tracheotomy was often
used in this setting. However, it is almost always possible to avoid tracheotomy by
addressing the area of obstruction directly with a supraglottoplasty. Using a laser or
microlaryngeal instruments, the redundant mucosa and/or cuneiform cartilages are
excised and the shortened aryepiglottic folds released. Long-term results with this
approach have been very good (98% to 100% of patients satisfactorily improved) (10).
The occasional severely affected infant may still require a tracheotomy.
Laryngeal Stenosis
Laryngotracheal stenosis may be characterized by etiology, area involved (supraglottic,
glottic, or subglottic larynx), the nature of the stenosis, and the degree of stenosis. Most
subglottic stenosis is acquired. Before the introduction of long-term endotracheal
intubation and ventilation of neonates, the problem of laryngotracheal stenosis was
uncommon, and treatment was based on a fear of disrupting growth centers of the
pediatric larynx. It was assumed that in time the stenotic airway would grow enough to
allow for decannulation. Tracheotomy was therefore used in close to 50% of patients with
laryngotracheal stenosis. The number of patients with secondary acquired laryngotracheal
stenosis markedly increased as very low birth weight infant survival increased. Over the
ensuing years, advances in techniques of endotracheal intubation have decreased the
overall incidence of laryngotracheal stenosis in surviving neonates from almost universal
to close to 1%.
Laryngotracheal stenosis is considered congenital when there is no history of other
potential causes, including intubation. Congenital laryngotracheal stenosis is the second
most common cause of stridor in infants (9). The etiology is believed to be a failure or
incomplete recanalization of the laryngeal lumen that normally occurs by the tenth week
of gestation.
Subglottic stenosis is present in a full-term infant when the subglottic airway measures
less than 4 mm (or 3 mm in a preterm infant). The area of stenosis may often extend to
the trachea or to the glottic and rarely even supraglottic larynx. The nature of the stenosis
can be soft, firm, or a combination. A soft tissue stenosis may be due to submucosal
mucous gland hyperplasia, ductal cysts, fibrous, or granulation tissue. Firm stenosis may
be secondary to an abnormally shaped or thickened cricoid cartilage or mature scar tissue.
Endotracheal tube sizing has become the most widely used means for assessing the
degree of stenosis (Table 74.6) (11).

TABLE 74.6. CLASSIFICATION OF
LARYNGOTRACHEAL STENOSIS BY
ENDOTRACHEAL TUBE SIZING



The treatment of subglottic stenosis must be individualized as each patient presents with
multiple variables that require consideration in addition to the degree of stenosis,
including the amount of extension out of the subglottis, the patient's general medical
condition, swallowing ability, age, and weight. Options for surgical management include
endoscopic techniques, expansion procedures (including splits and cartilage grafting),
and partial cricotracheal resection.
The ultimate goal of laryngotracheal reconstruction is tracheotomy decannulation or
prevention. The rate of decannulation varies with the severity of stenosis and the method
of reconstruction. Patients with 50% to 70% stenosis can dissimulate or avoid
tracheotomy in 81% to 88% with a single reconstructive procedure and in up to 97% after
two procedures (12). Single-procedure success rates in patients with 70% to 99% stenosis
are 78% to 81% and increases up to 91% after revision surgery (13). The results for
surgical repair of 100% stenotic lesions has improved significantly with the more recent
use of partial cricotracheal resection, with decannulation obtained in more than 90% with
a single procedure (14). Earlier reports for 100% lesions using cartilage expansion were
uniformly worse with decannulation rates of 37% to 50% after a single attempt and up to
72% after multiple procedures (15).
Subglottic Hemangioma
Subglottic and tracheal hemangiomas are relatively uncommon and are benign congenital
vascular malformations derived from mesodermal rests. The lesions have a 2:1 female
predominance and account for 1.5% of all congenital laryngeal anomalies (16). Patients
are usually asymptomatic at birth. The onset of stridor occurs within the first 6 months of
life in 85% and 50% have cutaneous hemangiomas present at the time of diagnosis (17).
Anteroposterior soft tissue neck radiographs (high kilovoltage) usually reveal an
asymmetric subglottic narrowing. Biopsy is usually not needed to confirm the diagnosis
because of the typical appearance of a compressible, asymmetric, submucosal mass with
bluish or reddish discoloration most often found in the posterolateral subglottis (Fig.
74.9; see also Color Plate 20 following p. 370).

FIGURE 74.9. Endoscopic view of a posterior subglottic
hemangioma. (See also Color Plate 20 following p. 370.)



The expected natural history of subglottic and tracheal hemangiomas is rapid growth that
slows by 12 months, followed by slow resolution over the subsequent months to years.
Most will completely resolve by 5 years. However, there is an unacceptably high
mortality rate when these lesions are left untreated. The decision of what therapeutic
measures to undertake therefore needs to be directed at maintaining the airway while
minimizing potential long-term sequelae of the treatment itself. Current management
options that have been reported include tracheotomy, laser partial excision, open surgical
resection, systemic or intralesional steroids, and systemic interferon alfa-2A.
Laryngeal Papillomatosis
Infection in the mucosa of the upper aerodigestive tract by human papillomavirus (HPV)
is expressed as recurrent respiratory papillomatosis (RRP). The most common viral
subtypes involved are HPV-6 and HPV-11. The viral particles are known to be widely
present in the mucosa of infected individuals but only expressed at certain locations in the
form of papillomas. These areas have traditionally been thought to be regions of
squamociliary junction (such as the vocal cords) and areas of injury (such as a
tracheotomy site) (18). The papillomas tend to be extensive and recurrent in the juvenile
form, usually presenting as dysphonia and airway obstruction (Fig. 74.10 and Fig. 74.11;
see also Color Plate 21 following p. 370).

FIGURE 74.10. Lateral airway radiograph showing
obstructing lesion at the glottic level in a 4-year-old
patient at the time of presentation with laryngeal
papillomatosis.



FIGURE 74.11. Endoscopic view of the same patient
with obstructing laryngeal papillomatosis. (See also Color
Plate 21 following p. 370.)



HPV is also responsible for genital papilloma, and half of all children with RRP were
born by vaginal delivery to mothers with active disease in the birth canal. This may be an
even greater percentage because of underreporting of active disease or undiagnosed
subclinical infection. However, the rate of transmission in the birth canal seems very low
(1% to 3%) (18,19). In addition, HPV transmission to children born by cesarean section
is unusual but has been reported. The incomplete protection of cesarean section is
potentially due to prenatal viral transmission. The mode of transmission of this disease is
therefore controversial, and cesarean delivery is not routinely recommended to patients
with genital papilloma (20).
The natural course of RRP is extremely variable, with no obvious patient-related risk
factors to aid in prognosis. Many cases have been seen to spontaneously regress in
adolescence, but others go on to extensive disease involving the trachea and pulmonary
parenchyma with a high fatality rate from untreatable airway obstruction. Rarely, the
papilloma may undergo malignant degeneration to squamous cell carcinoma. For this
reason, interval histologic examination of the obstructing tissue is important.
No medical or surgical therapy has been shown to reliably cure RRP, and most patients
spontaneously recover after a variable period of time with clinical disease. Treatment is
therefore aimed at maintaining a patent airway and usable voice and avoiding permanent
injury to the airway. The CO
2
laser has been the most common tool used for debulking of
RRP. More recently, powered laryngeal instruments have been developed that allow for
RRP debulking with microscopic visualization but without the laser-associated risks to
the patient and operating room personnel.
Multiple agents have been suggested as primary or adjuvant therapies for RRP.
Interferon- is the most widely used. Others include indole compounds, antiviral therapy,
and phototherapy with hematoporphyrin dye potentiation.
The role of tracheotomy in the treatment of RRP is controversial. Patients with RRP who
require a tracheotomy have a 50% rate of tracheal spread (21). However, it is not clear
whether these patients have distal spread because of the tracheotomy or if this subgroup
represents patients with very active disease and a high propensity for distal spread.
Regardless, some patients clearly require tracheotomy. In these cases, the clinician should
keep in mind the goal of decannulation as soon as possible.
Vocal Fold Paralysis
Vocal fold paralysis accounts for about 10% of congenital laryngeal lesions. Common
presenting symptoms of bilateral paralysis are a high-pitched inspiratory stridor, an
abnormal cry, and choking spells. The diagnosis is best made with awake flexible
laryngoscopy.
The underlying cause of vocal fold paralysis is often difficult to determine. A variety of
traumatic, neoplastic, inflammatory, and congenital lesions may result in laryngeal
paralysis with the vocal cords resting near the midline. In otherwise healthy neonates, the
paralysis is frequently transient. This may be related to obstetric trauma in the form of a
stretch injury to the recurrent laryngeal nerves. The remainder of congenital bilateral
paralysis is typically of central origin, either associated with the Arnold-Chiari
malformation and caudal displacement of the brainstem, the result of motor nuclear
dysgenesis, or related to an increase in intracranial pressure. If treated early, paralysis
caused by increased intracranial pressure often responds to cerebrospinal shunting or
posterior fossa decompression. Acquired paralysis can be a complication of cervical or
mediastinal (cardiac) surgery.
Vocal fold paralysis in infants usually resolves within 6 to 18 months. However, function
is unlikely to return if there is no sign of improvement within 2 to 3 years; therefore, a
watchful waiting is appropriate management for the initial 2+ years. A temporary
tracheotomy is usually, but not always, necessary to get to that point. A wide variety of
possible surgical approaches to improve the airway in patients with bilateral vocal fold
paralysis suggests that no one procedure is ideal. The goal is to restore the glottic airway
by lateralizing one or both of the paralyzed vocal cords. Reinnervation techniques are of
unclear utility and are currently rarely used.
Surgical lateralization procedures for bilateral vocal fold paralysis are to some degree
injurious to the developing larynx. Excisional procedures, in which tissue is removed
from the posterior glottis, may be done in an open fashion or endoscopically using the
surgical laser. Experience with laser arytenoidectomy or posterior cordotomy has been
good (22), with most patients being decannulated after a single treatment. Because the
tissue excision is primarily within the posterior larynx, long-term voice results are
typically acceptable. Also, if care is taken to avoid overly aggressive resection, aspiration
is rarely a problem. The most common late complication is failure to achieve an adequate
airway. Better results may be obtained using external approaches in children (23).
Possible options include arytenoidectomy, arytenoidopexy, or laryngeal expansion with
costal cartilage augmentation to the posterior cricoid plate.
Vascular Anomalies
Congenital anomalies of the great vessels account for about 5% of cases of stridor in
children. Airway symptoms are due to tracheal or bronchial compression. Vascular
anomalies that cause tracheal compression include vascular rings (double aortic arch) and
pulmonary slings (Fig. 74.12). The aberrant right subclavian artery is the most common
mediastinal vascular anomaly. However, because of its retroesophageal course, affected
patients may have dysphagia but not significant airway compromise. Because the
innominate artery normally passes from its origin on the aortic arch left of midline across
the anterior trachea to the right side, innominate artery compression of the trachea is not
associated with a true vascular anomaly. It has been hypothesized that in patients who are
symptomatic, the innominate artery is more taut than normal, the tracheal cartilages are
unusually compliant and more easily compressed, or that dilatation of other structures
such as the heart, esophagus, or thymus cause mediastinal crowding. The most common
symptomatic true vascular ring is the double aortic arch, which occurs if the fourth
branchial arches and the dorsal aortic root persist on both sides.

FIGURE 74.12. Vascular anomalies causing tracheal
compression.



The right arch is usually larger than the left, and part of the ring may be an atretic fibrous
band. A persistent right aortic arch and left ligamentum arteriosum also can form a
complete ring. The pulmonary artery sling is the most symptomatic of the
noncircumferential vascular anomalies and occurs when the left sixth arch resorbs and the
left pulmonary artery arises as a large collateral artery from the right pulmonary artery
and passes between the esophagus and trachea to perfuse the left lung. This anomaly
commonly results in significant compromise of the right mainstem bronchus and airway
symptoms. In addition, 30% of patients with pulmonary artery slings have associated
complete tracheal rings (Fig. 74.13; see also Color Plate 22 following p. 370) (24).

FIGURE 74.13. Endoscopic view of complete tracheal
rings. (See also Color Plate 22 following p. 370.)



Respiratory compromise from tracheobronchial vascular compression is potentially life
threatening but can present with subtle symptoms. Frequently, a high index of suspicion
is required to make the diagnosis. Patients with significant vascular compression usually
present early, with stridor that is biphasic and frequently associated with expiratory
grunting. Other presenting symptoms include a chronic cough, recurrent bronchitis and
pneumonia, difficulty feeding and failure to thrive, and occasionally reflex apnea. Reflex
apnea has been described as a reflexive respiratory arrest of variable duration that is
secondary to stimulation of vagal afferent nerve fibers during swallowing and other forms
of transient intrathoracic pressure changes.
Chest radiographs may provide some evidence of tracheal compression, and a barium
esophagram can show relatively characteristic filling defects that correspond to the
various types of vascular compression. However, once vascular compression is
suspected, the diagnostic modality of choice is computed tomography or magnetic
resonance imaging, which will clearly demonstrate the mediastinal vascular anatomy and
the size of the lower airway. Although today the diagnosis of vascular compression is
usually known before undergoing endoscopy, bronchoscopy also reveals characteristic
findings of compression depending on the type of vascular ring or sling. Bronchoscopy
also provides an immediate visual assessment of the surgical results on relieving the
compression and the degree of residual tracheomalacia present.
Nonsurgical management may be effective for most innominate artery compression and
loose vascular rings and slings that are mildly symptomatic. In contrast, moderately to
severely symptomatic patients usually require surgical repair. Absolute indications for
surgical treatment include reflex apnea, failure of medical management of severe
respiratory distress after 48 hours, and prolonged intubation. Relative criteria include
repeated episodes of lower respiratory tract infections; exercise intolerance; significant
dysphagia with failure to thrive; or coexisting subglottic stenosis, asthma, cystic fibrosis,
or previous tracheoesophageal repair.
Laryngeal Dyskinesia, Exercise-induced Laryngomalacia, and Paroxysmal Vocal Fold
Motion
This group encompasses a set of disorders resulting from laryngeal neuromuscular
dysfunction. Laryngeal dyskinesia has been described as a cause of stridor in infants. The
disorder is associated with gastroesophageal reflux and is distinct from adductor
paralysis. The stridor usually is not severe and resolves in the first year of life (25).
Exercise-induced laryngomalacia is believed to be an occasional cause for asthmalike
symptoms in older children and adolescents. Increased inspiratory airflow presumably
causes entrainment of the aryepiglottic folds into the glottic portion of the airway,
resulting in subtotal occlusion. The condition is diagnosed endoscopically while the
patient exercises. Paradoxical vocal cord motion (adduction during expiration) usually
presents in patients previously diagnosed with asthma who have not responded to the
usual treatment for reactive airway disease. The condition is often associated with
psychological problems (26).
Gastroesophageal Reflux Disease
Gastroesophageal reflux into the esophagus is a normal phenomenon. As is frequently
seen in infants, during some episodes of gastroesophageal reflux, the refluxate can pass
into the pharynx and expelled out the mouth. The frequency of gastroesophageal reflux is
age dependent. When gastroesophageal reflux results in systemic, gastrointestinal, or
respiratory symptoms, it is considered pathologic and labeled GERD (27). The most
frequent complications of GERD in children are failure to thrive and recurrent pulmonary
symptoms. Many pediatric patients do not have vomiting, dysphagia, or heartburn. This
silent aspect of GERD and respiratory tract symptoms often leads to misdiagnosis (28).
GERD has been implicated in numerous respiratory tract disorders, including otitis
media, sinusitis, laryngitis, laryngotracheal stenosis, recurrent pneumonia, and apnea.
Symptoms are mediated through direct gastric acid-induced mucosal inflammation and
through stimulation of protective airway reflexes. Reflux into the mid or upper esophagus
may induce a reflex laryngospasm causing apnea and/or exacerbate existing reactive
airway disease. An increased incidence of GERD has been observed in premature infants
with bronchopulmonary dysplasia, in neurologically impaired children, and in children
with congenital anomalies of the esophagus.
GERD associated with mild respiratory symptoms will often respond to a conservative
antireflux regimen alone. Children should be fed small frequent feedings. Formula should
be thickened with rice cereal up to 1 tablespoon per ounce of formula. Infants should
remain upright for 1 hour after feedings. Older children and adults should not eat for 3
hours before bedtime. Foods containing caffeine, chocolate, and acidic juices should be
avoided. For more significant symptoms, therapy will often include antireflux medical
therapy. Pharmacologic agents for GERD include H
2
blockers and proton pump inhibitors
that decrease the acid content of the stomach and prokinetic agents that promote gastric
emptying. Patients are then followed at 6-week intervals with management adjusted as
symptoms diminish. With severe symptoms, surgical antireflux treatment
(fundoplication) may need to be considered (4).
Laryngotracheobronchitis
Viral laryngotracheobronchitis, otherwise known as croup, is the most common
infectious cause of stridor, affecting 3% to 5% of all children at least once. Less than 5%
to 10% require hospitalization. Although children of any age can be affected, the peak
incidence appears to be in the second year of life. The most common causative virus is
parainfluenza virus type 1. Other viruses associated with croup include parainfluenza
virus types 2 and 3, respiratory syncytial virus, and influenza virus A.
Croup usually initiates as an upper respiratory tract infection and develops into a barking
cough and varying degrees of respiratory difficulty with an inspiratory high-pitched
stridor. The process develops over the period of 1 to 2 days and may last as long as 1 to 2
weeks before resolving. The child's appearance is usually not toxic.
Radiographic studies are not routinely indicated unless the diagnosis is in doubt. An
anteroposterior soft tissue neck radiograph will reveal the classic steeple sign
symmetric narrowing of the subglottic space. Associated findings on lateral soft tissue
neck radiographs include dilation of the hypopharynx and a normal-appearing
retropharynx and epiglottis.
Treatment of viral laryngotracheobronchitis depends on the clinical findings of the child.
In mild cases, those limited to a barky cough and minimal stridor without increased work
of breathing may be managed in an outpatient setting. Humidification is recommended
but not definitively proven efficacious. When the audible stridor is associated with
significant increased work of breathing and/or anxiety, hospital admission or observation
may be worthwhile. Oxygen in conjunction with water vapor mist given in a monitored
setting is helpful in cases of documented hypoxemia. The use of corticosteroids, once
controversial, is now a routine part of the management using primarily dexamethasone at
a dose of 0.6 to 1.0 mg/kg. Other medical treatment includes the use of nebulized racemic
epinephrine. Racemic epinephrine has a strong vasoconstrictive effect on the subglottic
mucosa but often must be repeated due to its transient effect and rebound edema.
Children who receive a course of racemic epinephrine must be observed for a period of at
least a few hours before considering discharge to home.
Fewer than 5% of hospitalized children develop respiratory failure and require
mechanical airway intervention. In these cases, nasotracheal intubation is preferred and is
usually necessary for 4 or 5 days. Patients who fail extubation or require repeated
hospitalization for croup should undergo direct laryngoscopy and bronchoscopy to search
for subglottic stenosis or other underlying abnormalities.
Acute Supraglottitis (Epiglottitis)
Acute supraglottitis is the result of an infection of the epiglottis and other supraglottic
structures. In the pediatric age group, it most commonly occurs in children between 1 and
5 years of age. Haemophilus influenzae type B is usually the causative agent. In
adolescent and adult cases, gram-positive organisms become more likely. The child with
acute supraglottitis presents with a history of rapid progression from mild upper
respiratory infection to respiratory distress, fever, and severe throat pain within hours.
Characteristically, the child assumes a sitting posture with the chin up and mouth open.
Fifty percent of patients with epiglottitis have extraepiglottic sites of infection at the time
of presentation, including meningitis, otitis media, pneumonia, and cellulitis. The child
with suspected supraglottitis is kept under constant observation. Great care is taken to
avoid agitating the child, and manipulation of the airway is contraindicated. History and
hands-off observation are usually sufficient for the diagnosis. Only when the diagnosis
is in question are portable lateral airway films helpful in delineating epiglottic swelling
(the thumb print sign) and dilation of the pharyngeal airway, confirming the diagnosis.
The child is taken to the operating room to establish an airway. The patient is intubated
orally after a careful halothane and oxygen induction and placement of an intravenous
line. The otolaryngologist can perform a direct laryngoscopy, obtains blood and epiglottis
cultures, and may consider replacing the oral endotracheal tube with a nasotracheal one.
Emergency tracheotomy is rarely needed and is not performed electively after
endotracheal intubation. Once the airway is secure, a search for extraepiglottic sites of
infection can proceed. Antibiotic therapy is started with chloramphenicol and ampicillin,
or ceftriaxone, and is modified as blood cultures become available. Extubation can be
considered when there is an air leak around the endotracheal tube at less than 20 cm H
2
O
pressure, which usually occurs within 48 hours of admission to the intensive care unit.
In 1985, the first vaccine for H. influenzae type B was introduced in the United States.
The initial monovalent vaccine suffered from low immunogenicity and was not effective
in children less than 18 months of age. In 1987, conjugate vaccines were released that
were effective in children greater than 2 months of age. After the introduction of the
conjugate vaccines, distinctive epidemiologic trends in H. influenzae disease have
emerged (29). There has been a dramatic decline in the overall incidence of supraglottitis
in the pediatric age group, whereas the incidence in adolescents and adults has remained
unchanged. Therefore, patients with supraglottitis tend to be older, and other pathogens
such as Candida albicans, staphylococcus, and Haemophilus parainfluenzae are more
likely to be recovered.
Bacterial Tracheitis (Membranous Tracheitis)
Membranous laryngotracheobronchitis has some clinical features of both viral
laryngotracheobronchitis and supraglottitis. The age range of affected children extends
from a few weeks to the early teenage years. The pathogenesis is unclear but is thought to
represent a complication of viral laryngotracheobronchitis. Membranous
laryngotracheobronchitis is often preceded several days by an upper respiratory tract
infection. A sudden change with rapid progression of a harsh, inspiratory, or biphasic
stridor and respiratory distress then occurs over several hours. Like supraglottitis, the
patient appears toxic and high fever is common. However, the patient is not drooling and
is usually able to lie flat. Soft-tissue lateral radiographs may show irregularities of the
airway, suggesting membranous-like debris, and persist on a repeat radiograph after an
effective cough. When a patient with suspected laryngotracheitis does not respond to a
racemic epinephrine trial, the possible diagnosis of membranous
laryngotracheobronchitis should be entertained. When suspected, bronchoscopy is
necessary for the removal of the adherent thick secretions that can obstruct the airway.
Endotracheal intubation is usually maintained postoperatively to assist with aggressive
pulmonary toilet.
Antibiotic therapy is directed toward the most common causative agent, Staphylococcus
aureus. Less commonly implicated agents include H. influenzae, Streptococcus pyogenes,
Streptococcus pneumoniae, and parainfluenza virus. Empirical antibiotic therapy is
directed toward the most common organisms and adjusted after culture results are known.
General Principles of Airway Management
Recognizing respiratory failure is the initial priority during the management of the
stridorous patient (30). Adequate airway resuscitation equipment must be maintained in
any setting where patients with stridor present. When necessary, ventilation is assisted or
controlled by positioning the patient with the head extended and the lower jaw thrust
forward. Secretions are cleared with suction. Placing a ventilating mask with a self-
inflating bag over the nose and mouth and applying positive pressure ventilation with
100% oxygen usually enables the rescuer to stabilize the patient before moving to a
controlled setting or attempting definitive airway management.
If positioning and positive airway pressure is not adequate for ventilation, the clinician
prepares for endotracheal intubation. A laryngoscope with appropriately sized blades,
assorted sizes of endotracheal tubes, and suction are arranged before attempting
intubation. For children older than 2 years, the appropriately sized (internal diameter)
endotracheal tube can be estimated by dividing the child's age (in years) by 4 and then
adding 4.
Rarely, endotracheal intubation with an endotracheal tube or bronchoscope is impossible,
and the rescuer must attempt emergency tracheotomy. Cricothyroidotomy is not
recommended in infants and young children because of the narrow cricothyroid
membrane. Some surgeons recommend needle cricothyroidotomy with a large-bore
intravenous catheter. The risks of emergency tracheotomy include failure to establish an
airway, inadequate gas exchange, esophageal perforation, and uncontrolled bleeding.
Once the airway has been secured, the patient is placed in a controlled setting for further
assessment and management. This usually requires transfer to the operating room for
airway endoscopy and surgery. Stridorous patients who do not appear to be at risk for
respiratory failure can be managed more electively after a complete diagnostic
evaluation.
Basic support measures keep the patient as comfortable as possible with minimal
intervention. Acetaminophen is used for fever control. Cooling blankets and tepid baths
are of little benefit in febrile patients with airway disease. Increased humidity in inspired
air loosens secretions and improves patient comfort. Oxygen therapy is used to manage
hypoxemia and is monitored with pulse oximetry and transcutaneous or arterial blood gas
determinations. Specific medical therapy depends on the diagnosis.
Complications
Otolaryngologists who deal regularly with airway obstruction appreciate the higher than
average risk of serious complications. The incidence of serious complications is unknown
but probably varies considerably depending on the etiology of airway compromise.
Obviously, respiratory arrest with death or anoxic brain injury is the most devastating
complication. Unfortunately, anoxic injury can result from the airway lesion itself and
can go unrecognized until after the physician has intervened. When possible, the
physician should have a frank and thorough discussion with the patient or family
regarding the risks of the disorder and its management.
Postobstructive pulmonary edema can present after the airway has been secured and
obstruction alleviated. The typical findings include hypoxemia, copious pink and frothy
secretions, bilateral end-expiratory wheezing with rales, and radiographic findings on
plain chest films of increased pulmonary vascular markings and fluid overload.
Treatment includes fluid restriction, diuretics, and continuous positive airway pressure.
Other common complications of endotracheal intubation and tracheotomy include
accidental extubation, tracheal plugging with inspissated secretions, laryngeal and
tracheal stenosis, and pneumothorax.
ASPIRATION
Evaluation and Diagnosis
A small amount of aspiration occurs normally, particularly during sleep; cough and
mucosal ciliary action usually clear the aspirate. Therefore, only when bronchopulmonary
complications occur is aspiration considered pathologic. Predisposing factors for
pathologic aspiration include altered mental status, neurologic swallowing disorders, and
local abnormalities of the aerodigestive tract (Table 74.7).

TABLE 74.7. DIFFERENTIAL DIAGNOSIS OF
CHRONIC ASPIRATION



The pulmonary consequences of aspiration vary with the duration of the underlying
disorder and the type of aspirate. The potential airway sequelae of aspiration include
chronic cough and hoarseness, pneumonia, pulmonary abscess, airway obstruction, and
pulmonary fibrosis. Factors that predispose aspiration to cause respiratory disease include
the bacterial load and pH of the material aspirated, the location of the aspiration event
(hospital vs. community), and the host defense mechanisms. Hospital-acquired aspiration
pneumonia is more likely to involve resistant organisms than that which occurs within the
community.
Clinical respiratory findings are not specific for aspiration. These include fever,
tachypnea, wheezing, and pulmonary rales. Radiographic changes tend to occur in the
dependent lung segments, particularly in the lower lobes.
Aspiration resulting from altered mental status occurs during alcohol or sedative
intoxication, head injury, cerebrovascular accident, or anoxic brain injury. These
conditions predispose to aspiration through loss of the cough and laryngeal swallowing
reflexes.
The clinical features of neurogenic aspiration vary between upper motoneuron lesions
and those affecting lower motor neurons, the neuromuscular junction, and the muscle
cell. Diseases that affect upper motor neurons tend to cause a spastic type of dysphagia
and aspiration associated with straining or strangling. These lesions are bilateral and
involve the motor cortex or brainstem. Lower motor neuron disorders produce a flaccid
muscular paralysis. Associated swallowing dysfunction presents with weakness in the
oral and pharyngeal muscles and prominent aspiration, especially when swallowing
liquids. Lower motoneuron swallowing dysfunction also results from diseases of the
neuromuscular junction and the muscle itself. Aspiration due to swallowing disorders is
classified by phase of swallowing. Aspiration during the preparatory and oral phases is
due to altered tongue anatomy or inadequate tongue movement. During the pharyngeal
phase, aspiration occurs because of poor pharyngeal peristalsis or inadequate laryngeal
sphincter function. Aspiration during the esophageal phase results from mechanical
obstruction or abnormal aerodigestive communications.
Three possible sources of aspirated material are orally ingested material, oral cavity and
oropharyngeal secretions, and regurgitated gastric contents. Oropharyngeal secretions are
the most commonly aspirated substances. Clinical sequelae relate directly to the bacterial
content of the secretions. Anaerobic bacteria are the predominant pathogens in
nonhospitalized patients. Oropharyngeal microorganisms, including Bacteroides
melaninogenicus, Fusobacterium, and anaerobic gram-positive cocci, are the dominant
isolates. Gram-negative organisms, including Pseudomonas, are the predominant isolates
in patients experiencing aspiration during hospitalization. The bacterial load of oral
secretions is increased by poor oral hygiene among other things.
Gastric contents are the second most commonly aspirated substances. Solid food particles
can cause upper airway obstruction with asphyxia or lower airway obstruction with
pneumonia and atelectasis. Normally, the gastric contents have a pH less than 4 that when
aspirated may cause a chemical pneumonitis, but the bacterial load will be low because of
suppression by the low pH. When H
2
blockers or proton pump inhibitors raise the pH, the
bacterial load of stomach contents increases. This increases the risk for bacterial
contamination of the airway from gastroesophageal reflux-associated aspiration.
Aspirated gastric contents also contain bacteria.
Gastroesophageal reflux can lead to a more indolent form of chronic aspiration. These
patients often complain of a persistent cough, throat discomfort, and fluctuating
hoarseness. Throat clearing, wheezing, and dyspnea develop in some patients. Routine
laboratory studies and chest radiographs are normal. Laryngoscopy can be diagnostic and
reveals posterior laryngeal erythema, edema, and exudation. Antireflux therapy is usually
curative.
Foreign-body aspiration is primarily a pediatric malady; half of the cases occur in
children younger than 5 years. Proximal airway impaction presents as acute stridor and
may lead to tracheal obstruction with asphyxia before the child reaches a treatment
facility. Foreign bodies lodged in the bronchi cause expiratory wheezing and obstructive
emphysema. Pneumonia and atelectasis are late sequelae.
Evaluation: Radiography and Special Diagnostic Studies
Rehabilitative Swallow Study
The rehabilitative swallow study examines upper aerodigestive function using a modified
barium swallow technique and videofluoroscopy (31). During the study, the patient
assumes a normal upright eating posture and swallows feedings of varying consistency
mixed with a small amount of barium. The swallowing therapist and radiologist perform
the study in the fluoroscopy suite. The image is adjusted to view the lips, soft palate,
posterior pharyngeal wall, and cervical esophagus.
Generally, three feeding consistencies are studied: liquid (dilute barium), paste (thickened
barium, Esophatrast), and solid (shortbread cookie coated with thickened barium). Small
feedings (one third of a teaspoon) are used to outline the aerodigestive structures while
limiting aspiration. Infants are fed formula with a small amount of barium. Syringe
feeding may be needed to complete the study in patients with abnormal preparatory or
oral swallowing phases. During fluoroscopy, the therapist observes the motion and
coordination of the four swallowing phases, noting the effects of positioning and
compensatory posturing. Persistent pharyngeal residue, dry swallowing (a normal
response to pharyngeal residue), and aspiration are also recorded.
Functional Endoscopic Evaluation of Swallowing
The functional endoscopic evaluation of swallowing involves positioning a flexible
nasopharyngoscope just posterior to the soft palate, allowing observation of the
hypopharynx and larynx while the patient is fed various consistencies of food dyed with
coloring to aid visualization. Parameters that can be evaluated include pharyngeal
pooling, premature spillage, laryngeal penetration, aspiration, and residue. The benefits
of this technique over the rehabilitative swallow study include the ability to assess
pharyngeal sensation and the absence of radiation exposure, which allows a longer period
of observation and frequent follow-up examinations during which multiple feeding
strategies can be tested. The disadvantages include that the test is mildly invasive and
evaluation is limited to the events immediately before and immediately after the swallow
event. In addition, the preparatory and oral phases of the swallow can only be indirectly
evaluated. The esophageal phase cannot be evaluated at all with this method of testing.
Imaging Techniques
Plain radiographs have limited application in the evaluation of aspiration. Occasionally,
structural abnormalities, soft-tissue masses, or cervical spine deformities can be
diagnosed. Computed tomography and magnetic resonance imaging can detect
intracranial lesions affecting the brainstem and lower cranial nerves. Magnetic resonance
imaging is especially useful in detecting tumors and anomalies in the posterior fossa (e.g.,
Arnold-Chiari malformation).
Manometry
Manometry measures the pressure changes in a catheter passed through the pharynx into
the esophagus. The clinical application in aspiration is limited to assessment of
cricopharyngeal dysfunction and is most useful when coupled with videofluoroscopy.
Ultrasound
Real-time ultrasonography has been applied recently to swallowing evaluation. The
technique is well suited for studying the oral swallowing phase because it avoids the use
of radiation and allows visualization of the actual tongue surface instead of the
swallowed bolus. Abnormalities of tongue movement, tongue and palate approximation,
and hyoid elevation can be detected.
Radionuclide Scintigraphy
Radionuclide scintigraphy with swallowed technetium complements the rehabilitative
swallow study and can measure the severity of aspiration. The patient swallows a small
amount of water with technetium 99m and lies under the scintillation camera with a
computerized counting device. The radiologist compares the amount of radioactive
material entering the lung to the total radioactive count and calculates the percentage of
aspiration.
Electromyography
Much of our understanding of swallowing physiology is derived from oropharyngeal and
laryngeal electromyography. Increasingly, electromyography contributes to clinical
diagnosis in swallowing disorders. The technique's principal advantage in evaluating
aspiration is that it permits the study of individual muscles during swallowing.
Bipolar surface electrodes are most commonly used to record the myoelectric activity of
the pharyngeal constrictors, the thyroarytenoid and the cricopharyngeal muscles.
Myoelectric patterns occur as tonic, phasic, or absent. Information gained from
electromyography enables the clinician to distinguish between brainstem and spinal
column lesions (upper motoneuron) and peripheral nerve lesions (lower motoneuron).
Management
Medical Management and Swallowing Rehabilitation
Some patients with aspiration pneumonia require hospitalization in an intensive care unit
with respiratory therapy and facilities to manage respiratory failure. Intubation or
bronchoscopy may be needed for adequate pulmonary toilet. Initial antibiotic coverage
for nonhospital-acquired aspiration pneumonia should be effective against anaerobic
organisms. Penicillin, clindamycin, and chloramphenicol are logical empiric choices. An
aminoglycoside is added in cases in which the aspiration occurs during hospitalization.
The treatment of chronic aspiration requires a multidisciplinary approach, with the choice
of intervention determined by the severity and source of aspiration, the underlying
condition of the patient (medical and neurologic status), and the potential for
rehabilitation. Many cases of chronic aspiration secondary to swallowing dysfunction
respond to conservative dietary and rehabilitative treatment. Swallowing therapists can
work with patients by altering their food consistencies, adjusting their posture during
swallowing, and training them to exhale while swallowing. Palatal training appliances
have been used to increase tactile stimulation, providing an extra stimulus to trigger
involuntary swallowing. Medical management of GERD has been discussed earlier in this
chapter. Medical treatment of sialorrhea may include using antihistamines or more
specific anticholinergic agents. However, almost 50% of patients will discontinue
pharmacologic management of sialorrhea because of the high rate of significant side
effects, including constipation, urinary retention, xerostomia, blurred vision, and
restlessness.
Surgical Management
The otolaryngologist often consults for surgical management of life-threatening
aspiration. Surgical procedures for aspiration are appropriate for intractable cases that
cannot be controlled with more conservative measures. Most anatomic changes created
by these procedures are difficult or impossible to reverse. For the surgical management of
aspiration, the surgeon should select the appropriate procedure after carefully considering
the pathophysiologic abnormalities and associated factors such as previous surgery,
neurologic dysfunction, and malnutrition.
Alimentary Procedures
Feeding Gastrostomy and Jejunostomy
Alimentary bypass with a feeding gastrostomy or jejunostomy is indicated for chronic
aspiration associated with malnutrition. Although feeding gastrostomy and jejunostomy
are the most commonly used techniques for managing patients with severe irreversible
swallowing dysfunctions, they do not prevent aspiration of oropharyngeal secretions.
Fundoplication
Gastric fundoplication is indicated for gastroesophageal reflex associated with aspiration
pneumonia that has not responded to conservative antireflux regimens. The surgeon
lengthens the portion of the esophagus in the abdomen and attempts to create a valvelike
mechanism by wrapping the stomach around the lower esophageal sphincter. The Nissen
procedure and the Thal partial fundoplication are effective in relieving aspiration caused
by reflux. Reported complications include wound breakdown, esophageal obstruction,
inability to burp or vomit, and failure to control reflux.
Cricopharyngeal Myotomy
Cricopharyngeal myotomy is performed specifically for cricopharyngeal achalasia, a
condition in which the cricopharyngeal muscle fails to relax during the pharyngeal phase
of swallowing. Cricopharyngeal achalasia is diagnosed using the modified barium
swallow or manometry.
Cricopharyngeal myotomy involves a lateral cervical approach to the cricopharyngeal
muscle, which is divided over an esophageal bougie or cuffed endotracheal tube placed
into the esophagus. Magnification is helpful, and the surgeon must be careful to preserve
the underlying mucosa. Potential complications include wound infection and damage to
cranial nerves X and XI.
Control of Salivary Output and Sialorrhea
Adequate control of salivary output significantly improves the quality of life for those
with chronic aspiration of oropharyngeal secretions. Multiple procedures have been
reported in the literature for the surgical control of salivary output: salivary gland
excision, destruction of parasympathetic control fibers, ductal ligation, ductal rerouting,
or various combinations of the above. There is some controversy because each therapy
has its own advantages and disadvantages. Parasympathetic denervation is often initially
successful in the short term, but drooling usually recurs within 6 months. Ductal
rerouting to a more posterior position is often successful for anterior drooling, but the
increased amount of secretions pooling in the hypopharynx would contraindicate its use
in patients with problems aspirating oropharyngeal secretions.
Bilateral Submandibular Gland Excision with Parotid Duct Ligation
Removal of the submandibular glands eliminates most resting salivary flow. Ligation of
the parotid ducts eliminates the major source of food-stimulated salivary production. This
combination effectively decreases the sequelae from aspiration of oropharyngeal
secretions (32). Occasionally, a mild noninfectious parotitis will occur that usually
resolves spontaneously within 1 to 2 weeks. Rarely, acute parotitis may require
antimicrobial therapy. Xerostomia with its associated increase in dental caries may occur.
However, salivary production from the minor salivary glands continues to produce an
adequate amount of saliva to prevent xerostomia in most patients. Some are now
advocating the ligation of submandibular ducts along with the parotid ducts, thereby
avoiding the external incisions associated with submandibular excision. Early reports
have not shown an increase in submandibular gland infections.
Laryngeal Incompetence Procedures
Tracheotomy
Tracheotomy is indicated as a temporary solution for severe aspiration with pulmonary
complications, particularly in unstable patients. The procedure is readily performed and
provides access for pulmonary toilet. A cuffed tracheotomy tube decreases aspirated
material but increases the risk potential tracheal dilation and ulceration. The tracheotomy
may also increase aspiration by limiting laryngeal elevation. Anticipated chronic
aspiration requires a more definitive procedure.
Laryngectomy
Life-threatening aspiration after massive oropharyngeal cancer resection may require
laryngectomy. Because of its obvious morbidity and the availability of more physiologic
procedures, laryngectomy seldom is performed for this indication.
Laryngeal Suspension
Laryngeal suspension is indicated for aspiration due to lingual, pharyngeal, and
supraglottic laryngeal dysfunction, particularly after tumor resection for oropharyngeal or
supraglottic cancer. Suspension sutures are placed from the anterior or lateral thyroid
cartilage to the mandible, pulling the larynx anteriorly and superiorly to prevent spillage
into the glottis. This also opens the hypopharynx posteriorly, allowing easier passage of
food and secretions through the upper esophageal sphincter. The chief advantage is
maintenance of normal breathing, phonation, and swallowing. However, after massive
tumor resections, it may not adequately relieve aspiration, and further surgical
intervention may be needed.
Partial Cricoid Resection
Posterior cricoid resection is another procedure designed to alleviate aspiration after
extensive oropharyngeal resection. This procedure is performed at the time of primary
tumor surgery. A submucosal segment of posterior cricoid is resected in conjunction with
a cricopharyngeal myotomy. The resection leaves an enlarged hypopharyngeal portal for
food and secretions and narrows the laryngeal inlet. The procedure is irreversible and
requires a permanent tracheotomy.
Vocal Fold Medialization
Vocal fold medialization has been used for aspiration due to failure of glottic closure
during swallowing. The condition is most commonly due to vocal fold paralysis. The
endoscopic approach involves endoscopic or percutaneous injection of a paralyzed vocal
fold with Teflon. Glycerin and Gelfoam have been used for temporary treatment. The
external approach involves unilateral or bilateral thyroplasty. Both require the presence of
a tracheotomy. Most reports using these procedures have a 50% success rate in
controlling aspiration. Complications include poor voice, granulation tissue formation,
and airway obstruction. Teflon injection for vocal fold medialization is not easily
reversible.
Laryngeal Closure
Procedures for laryngeal closure include epiglottic closure or glottic closure. Either can
be done using an endoscopic or external approach. The procedures leave a small posterior
aperture for vocalization. Both require the presence of a tracheotomy and have a 50% to
80% success rate. Dehiscence of the closure is a problem that may be improved by the
injection of botulinum toxin to limit laryngeal movement during the healing process.
Laryngeal Diversion and Separation
The use of laryngotracheal separation or tracheoesophageal diversion in pediatric patients
has been well documented, with a greater than 90% success rate. These procedures allow
complete separation of the airway from the digestive tract, thus eliminating the risk of
aspiration. Several surgeons have described laryngotracheal separation, a modification of
Lindeman's original (1975) diversion procedure (Fig. 74.11). The larynx and proximal
trachea are converted to a blind pouch, and a permanent tracheostomy is created. The
separation procedure is not technically difficult and is not associated with problems
resulting from stasis of food or secretions in the upper pouch. However, the possibility of
voice production is eliminated in addition to the need of a permanent tracheotomy stoma.
The procedure is reversible (33).
COUGH
Cough is a normal physiologic mechanism for clearing a foreign stimulus from the
respiratory tract. Chronic persistent cough is symptomatic of an underlying disorder and
requires further investigation to detect a specific etiology. Adequate treatment is possible
after a precise diagnosis has been established.
Evaluation
History and Physical Examination
Cough is one of the most common symptoms for which patients seek medical attention.
Most illnesses associated with cough are due to self-limited viral upper respiratory
infections. When cough becomes chronic or recurrent or serves no useful function, the
otolaryngologist may be consulted for more extensive evaluation. The initial history
concentrates on the duration and character of cough. Chronic productive cough is
associated with tracheobronchial disease; nonproductive cough is more likely due to an
upper airway lesion or asthma. Postnasal drainage and gastroesophageal reflux cause
cough associated with throat clearing. Active or passive smoking and exposure to
environmental toxins are common causes of chronic cough in adults. The consultant
should look for associated symptoms of allergies, recurrent upper respiratory infections,
or sinusitis.
A complete physical examination includes special attention to the head and neck,
respiratory passages, chest, and cardiovascular system. Indirect and direct fiberoptic
inspection of the nasopharynx, hypopharynx, and larynx is important. The ears should be
examined for cerumen impaction, inflammation, eczema, and irritation of the tympanic
membrane caused by hairs. It is helpful to have the patient cough voluntarily to
characterize the qualities of the cough and the amount of sputum production.
Laboratory Studies and Radiology
The initial workup for chronic cough includes a complete blood count with eosinophils, a
chest radiogram, and sputum examination for cytology, bacteria, tuberculosis, and
fungus. The chest radiogram may reveal pathologic processes that are not apparent on
physical examination. Comparing inspiratory and expiratory views may show
hyperinflation due to a radiolucent foreign body or endobronchial neoplasm.
A screening computed tomography of the paranasal sinuses evaluates possible underlying
sinusitis. These limited studies provide an overview of the sinuses while limiting the cost
and radiation exposure (to approximately the same amount as the traditional four-view
plain radiographic studies used in the past).
The clinician should request pulmonary function testing when there is a history of
chronic obstructive or restrictive lung disease. Methacholine challenge testing can detect
hyperactive airways and diagnose cough variant asthma, the most common cause of
chronic cough. In infants and small children or if the study is unavailable, a therapeutic
trial of albuterol may be used instead.
Endoscopy
If the initial workup, including laboratory and radiologic studies, is not diagnostic, the
otolaryngologist should consider endoscopy. Although endoscopy is not indicated as
often as in the workup for stridor or aspiration, it is useful in difficult diagnostic cases.
Complete airway inspection includes the larynx and the tracheobronchial passages.
Flexible bronchoscopy is most often performed in adults under topical anesthesia; the
rigid bronchoscope and general anesthesia are used in most pediatric cases. Common
endoscopic diagnoses in patients with chronic cough include congenital airway
anomalies, neoplasms, and foreign bodies.
Differential Diagnosis
Patients with acute cough (less than 4 months) have self-evident diagnoses and do not
require extensive evaluation. An approach to the diagnosis of chronic cough is best
considered from the perspective of the various receptor sites and afferent neurons of the
cough reflex (Table 74.8).

TABLE 74.8. DIFFERENTIAL DIAGNOSIS OF
COUGH ORGANIZED BY RECEPTOR SITES



Cough stimulants acting on the laryngeal and tracheobronchial receptors are numerous.
Tobacco smoke, environmental fumes, and allergens are probably the most common
external irritants. The hoarse wet cough associated with tobacco use (smoker's cough)
is caused by chemical irritation of both the upper and lower airways. Allergens are
thought to act on the airways directly and through the production of nasal and pharyngeal
secretions, with cough induced by postnasal drainage.
Cough is often a presenting symptom in chronic sinusitis. Adults usually have facial pain
or headache. Children usually have nasal drainage without pain. The cough due to
chronic sinusitis may be mediated by reflex mechanisms or may be associated with
inflammatory mediators common to the respiratory tract. It is usually wet and
nonproductive and is worse at night. Treatment consists of the appropriate diagnosis and
management of the underlying sinus infection.
Cough variant asthma probably results from bronchoconstriction and direct stimulation of
the bronchial rapidly acting stretch receptors or through mucus irritation of the C-fiber
endings (34). Cough variant asthma presents as nonproductive coughing without
wheezing. Peripheral blood smears for eosinophilia and routine pulmonary function tests
are normal. Bronchoconstrictor challenge testing is diagnostic, and the disorder responds
to bronchodilator therapy.
Reflux, pulmonary aspiration, pulmonary edema, lung infection, or neoplasm involving
the trachea or bronchi may trigger the cough reflex. Bronchogenic carcinoma should be
suspected in any smoking patient who has experienced an increase or change in the
character of cough. In restrictive lung disease, changes in intraluminal airway pressures
may stimulate the lung stretch receptors and result in cough.
Coughing may present as a nonspecific symptom from stimulation of other cough
receptors. Receptors in the pharynx respond to inflammation from pharyngitis, postnasal
drip associated with rhinitis or nasopharyngitis, and gastroesophageal reflux with reflux
laryngitis. Cough can also accompany illnesses that affect the ears, pleura, pericardium,
or stomach. Conditions that directly affect the afferent neurons and produce cough are
uncommon. Cough can occur with vagus neurilemomas and cranial nerve stimulation
from cervical osteophytes.
Management
Chronic cough responds to specific treatment of the underlying cause in over 80% of
cases (35). General therapeutic measures include smoking cessation, avoiding
environmental toxins, and controlling known allergic factors. Other types of specific
therapy for cough include antibiotics for documented infections, bronchodilators for
asthma, and antireflux regimens for gastroesophageal reflux.
When cough cannot be diagnosed and treated definitively or is so severe that it impairs
the patient's lifestyle, symptomatic treatment may be indicated. Many commonly used
cough remedies are known to have limited effectiveness or have simply not been studied
adequately to determine their usefulness. Cough remedies are classified as suppressants,
expectorants, or mucolytics. Many popular cough formulations contain combinations of
ingredients from more than one class.
Antitussives directly suppress the neural elements of the cough reflex. Their action may
be central or peripheral. Among the cough reflex suppressants, only the centrally acting
narcotics have well-documented effectiveness. Codeine phosphate is the most commonly
prescribed drug in this class. Other narcotics have an antitussive effect, but when given in
cough-suppressant doses, they have increased addiction potential and are not as well
tolerated. Dextromethorphan, a nonnarcotic centrally acting suppressant, is used often
and may be effective but has not undergone controlled study.
Peripheral cough suppressants act by anesthetizing the cough receptors. Topical lidocaine
(Xylocaine) is probably effective in controlling pathologic cough but is hampered by its
short duration of action and difficulties in nebulized administration.
Expectorants and mucolytic agents exert their antitussive activity by increasing the
volume of respiratory secretions and by decreasing mucus viscosity. Cough lozenges,
syrups, and humidity are common examples but can be irritants themselves. Glyceryl
guaiacolate and iodide are the most common expectorants found in combination cough
preparations. Both are unproven; moreover, iodides have the potential for significant side
effects, including skin eruptions, thyroid enlargement, and gastrointestinal symptoms.
Most proprietary cough remedies combine cough suppressants, expectorants,
decongestants, and antihistamines. Because their effectiveness has never been
documented, combination preparations should be avoided.

HIGHLIGHTS
Stridor, aspiration, and cough are symptoms of many
aerodigestive disorders. Adequate diagnosis depends on a
careful history and appropriate diagnostic studies.
Within the sphincter mechanism of laryngeal closure, the true
vocal folds form the most effective barrier to aspiration,
whereas the false vocal folds are the most effective in the
production of cough.
Respiratory rate and level of consciousness are the most
important indicators of respiratory distress in the patient with
stridor. Respiratory phase is the most useful physical sign in
delineating a differential diagnosis of stridor.
Awake flexible fiberoptic endoscopy is the most useful
diagnostic technique to assess the upper airway without general
anesthesia.
The most challenging airway problems occur in children.
Assessment of stridor using the SPECS-R mnemonic (severity,
progression, eating difficulties, cyanosis, sleep disturbances,
and radiologic findings) can help the clinician decide if
intervention is needed.
Acute laryngotracheobronchitis is the most common cause of
acute stridor in children, whereas laryngomalacia is the most
common cause of chronic stridor.
Conjugate vaccines for H. influenzae type B have significantly
changed the epidemiology of acute supraglottitis. There are
fewer reported cases, and affected individuals tend to be older
and may have infection due to other organisms.
Recognition of respiratory failure is the initial priority during
the management of the stridorous patient.
Aspiration may occur in patients with altered mental status,
neurologic swallowing disorders, and abnormalities of the
aerodigestive tract. Oropharyngeal secretions and gastric
contents are the most commonly aspirated substances.
Initial antibiotic coverage for nonhospital-acquired aspiration
pneumonia should be effective against anaerobic organisms.
Penicillin, clindamycin, and chloramphenicol are logical
empiric choices; an aminoglycoside is added if the aspiration
occurs during hospitalization. Surgical procedures for aspiration
are appropriate for intractable cases that are not controlled by
more conservative measures.
Most illnesses associated with cough are due to self-limited
viral upper respiratory infections. When cough becomes
chronic or recurrent or serves no useful function, the
otolaryngologist may be consulted for more extensive
evaluation.
CHAPTER REFERENCES
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otolaryngology and head and neck surgery. New York: Elsevier, 1989:658673.
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Pediatric laryngology and bronchoesophagology. Philadelphia: Lippincott-Raven, 1997:4148.
3. Jasin M, Osguthorpe J. The radiographic evaluation of infants with stridor. Otolaryngol Head
Neck Surg 1982;90:736.
4. Barbero G. Gastroesophageal reflux and upper airway disease. Otolaryngol Clin North Am
1996;29:27.
5. Wilson J, White A, Von Haacke NP, et al. Gastroesophageal reflux and posterior laryngitis. Ann
Otol Rhinol Laryngol 1989;98:405.
6. Koufman, J The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a
clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an
experimental investigation of the role of acid and pepsin in the development of laryngeal injury.
Laryngoscope 1991;101:1.
7. Black D, Haggitt RC, Orenstein SR, et al. Esophagitis in infants. Gastroenterology 1990;98:1408.
8. Rudolph CD. Gastroesophageal reflux and airway disorders. Philadelphia: J.B. Lippincott,
1995:327357.
9. Holinger LD. Etiology of stridor in the infant, neonate and child. Ann Otol Rhinol Laryngol
1980;89:397.
10. Zalzal G, Anon J, Cotton RT. Epiglottoplasty for the treatment of laryngomalacia. Ann Otol
Rhinol Laryngol 1987;98:7276.
11. Myer C III, O'Connor D, Cotton RT. Proposed grading system for subglottic stenosis based on
endotreacheal tube sizes. Ann Otol Rhinol Laryngol 1994;103:319.
12. Lusk RP, Kang D, Muntz HR. Auricular cartilage grafts in laryngotracheal reconstruction. Ann
Otol Rhinol Laryngol 1993;102:247254.
13. Ochi J, Evans J, Bailey C. Pediatric airway reconstruction at Great Ormond Street: a ten-year
review, I: Laryngotracheoplasty and laryngotracheal reconstruction. Ann Otol Rhinol Laryngol
1992;101:465468.
14. Stern Y, et al. Partial cricotracheal resection with primary anastomosis in the pediatric age group.
Ann Otol Rhinol Laryngol 1997;106:891896.
15. Cotton R, Gray S, Miller R. Update of the Cincinnati experience in pediatric laryngotracheal
reconstruction. Laryngoscope 1989;99:11111116.
16. Holinger P, Brown W. Congenital webs, cysts, laryngoceles and other anomalies of the larynx.
Ann Otol Rhinol Laryngol 1967;76:744752.
17. Leikensohn J, Benton C, Cotton RT. Subglottic hemangioma. J Otolaryngol 1976;5:487492.
18. Kashima H, Mounts P, Leventhal B, et al. Sites of predilection in recurrent respiratory
papillomatosis. Ann Otol Rhinol Laryngol 1993;102:580583.
19. Smith EM, Johnson SR, Pignatari S, et al. Perinatal vertical transmission of human papillomavirus
and subsequent development of respiratory tract papillomatosis. Ann Otol Rhinol Laryngol
1991;100:479483.
20. Derkay C. Task force on recurrent respiratory papillomas: a preliminary report. Arch Otol Head
Neck Surg 1995;121:13861391.
21. Cole R, Myer C III, Cotton RT. Tracheotomy in children with recurrent respiratory papillomatosis.
Head and Neck 1989;11:226230.
22. Ossoff R, Duncavage JA, Shapshay SM, et al. Endoscopic laser arytenoidectomy revisited. Ann
Otol Rhinol Laryngol 1990;99:764.
23. Bower C, Choi S, Cotton RT. Arytenoidectomy in children. Ann Otol Rhinol Laryngol
1994;103:271.
24. Backer CL, Ilbawi MN, Idriss FS, et al. Vascular anomalies causing tracheoesophageal
compression. J Thorac Cardiovasc Surg 1989;97:725731.
25. Denoyeele F, Garabedian EN, Roger G, et al. Laryngeal dyskinesia as a cause of stridor in infants.
Arch Otol Head Neck Surg 1996;122:612616.
26. Miller DA, Kim JW, Bent JP, et al. Pediatric exercise induced laryngomalacia. Ann Otol Rhinol
Laryngol 1996;105:169175.
27. Burton DM, Pransky SM, Katz RM, et al. Pediatric airway manifestations of gastroesophageal
reflux. Ann Otol Rhinol Laryngol 1992;101:742.
28. Kennedy J. Silent gastroesophageal reflux: an important but little known cause of pulmonary
complications. Dis Chest 1962;42:42.
29. Gonzalez Valdepena H, Wald ER, Rose E, et al. Epiglottitis and Haemophilus influenza
immunization. The Pittsburgh experience: a five year review. Pediatrics 1995;96:424427.
30. Chameides L, ed. Textbook of pediatric advanced life support. Vol. 21. American Heart
Association. St. Louis: Annals Publishing, 1987.
31. Logemann J. Manual for the videofluorographic study of swallowing. San Diego: College Hill
Press, 1986.
32. Gerber M, Gaugler MD, Myer CM, et al. Chronic aspiration in children: when is bilateral
submandibular gland excision and parotid duct ligation indicated? Arch Otol Head Neck Surg
1996;122:13681371.
33. Blitzer A. Evaluation and management of chronic aspiration. N Y State J Med 1987;87:154.
34. Coirao W, Braman S, Irwin R. Chronic cough as the sole presenting manifestiation of bronchial
asthma. N Engl J Med 1979;300:633.
35. Fuller R, Jackson D. Physiology and treatment of cough. Thorax 1990;45:425.
36. Myer C III, Cotton RT. Pediatric airway and laryngeal problems. In: Leek; Textbook of
otolaryngology, head and neck surgery. Elsevier: New York, 1989:658673.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

75 PEDIATRIC TRACHEOTOMY
Head & Neck SurgeryOtolaryngology
75




PEDIATRIC TRACHEOTOMY
RONALD W. DESKIN

R.W. Deskin: Department of Otolaryngology, Baylor College of Medicine, Houston, Texas.


History
Tracheostomy Versus Prolonged Intubation
Technique
Postoperative Care
Hospital
Home
Complications
Tracheostomy Tubes
Decannulation
Communication Concerns
Summary
Chapter References
The management of airway problems in children is sometimes a difficult task and
necessitates thorough evaluation and thoughtful planning. The most important outcome is
a safe airway that can be managed comfortably with the lowest morbidity and mortality
by the team caring for the child.
The decision whether to manage a child with airway problems with endotracheal
intubation or with tracheostomy requires a team usually consisting of the child's
pediatrician, critical care intensivist, anesthesiologist, and otolaryngologist. The most
experienced team is desirable. In addition, in the decision-making time and the ongoing
management period, a team of nurse educators, speech pathologists, respiratory
therapists, social workers, and psychologists is helpful. Consideration of the experience
and availability of care in a given medical facility is also important. The parents are a
vital part of the team. Often it has been noted that when the subject of a tracheostomy
comes up, the initial response of a parent is very negative. After the decision has been
made and the tracheostomy completed, the parents' relief regarding this method of
management of the airway is often demonstrated by the question, Why didn't we do this
earlier? The third predictable response of the typical parent of a child with a
tracheostomy is at the time of consideration for decannulation, when the parent has strong
concerns and reservations about giving up the tracheostomy-managed airway.
Terminology is sometime confusing. Tracheotomy is derived from the Greek word tome,
meaning to cut. Tracheostomy is derived from the Greek word stomoun, meaning to
provide an opening. Specifically, tracheotomy refers to the surgical procedure and the
act of providing an opening into the trachea. Tracheostomy refers to the actual hole in the
trachea, and it is also used to describe the tube that is placed in the hole. The two words
are most often used interchangeably.
HISTORY
The history of tracheostomy includes references to windpipe incisions presented in the
Rigveda, a Hindu medicine book, written in 2000 BC (1). Alexander the Great is reported
to have opened the trachea with a sword in a soldier choking on a lodged bone in the
throat in the fourth century BC (1). The surgical procedure is also mentioned by surgeons
between 100 BC and 200 AD such as Asclepiades, Aretaeus, and Galen (2). From the
sixteenth century to 1830, the procedure seems to have fallen out of favor, and only 28
successful procedures were mentioned over 2,000 years (2). The first pediatric
tracheotomy reference was in a 7-year-old boy who aspirated a bone in 1650. This was
overruled as a risky procedure, and the child died anyway (3). In the early to mid-1800s,
a large number of cases of tracheostomy were reported in diphtheria patients.
Tracheostomy was often a last resort but resulted in a reported 32% survival rate (4).
Jackson published a text in 1907 and set the stage for progressive developments in
laryngology and bronchoesophagology (3). Some of his basic equipment designs and
techniques are still adhered to today, and subsequent discussions have used this as a point
of comparison. When general anesthesia began in the mid-1800s, tracheostomy was used
as a temporary airway. In the early 1900s, endotracheal intubation was introduced, and
tracheostomy became less popular. Immunization for diphtheria and sulfonamides for
other inflammatory airway problems decreased the need for tracheostomy (3).
In the 1930s, the polio epidemic reintroduced the usefulness of the tracheostomy (1). The
polio vaccines in the 1960s decreased this indication. As general anesthesia developed
and endotracheal intubation became worldwide, the comparison of endotracheal
intubation and tracheostomy became a popular controversy (5).
As the specialty of neonatal medicine developed, the desire to provide a safe airway for
sometimes long-term ventilation inspired many thoughtful studies of the advantages and
disadvantages of endotracheal intubation versus tracheostomy. Whereas the treatment of
acute airway inflammation was a frequent indication for tracheostomy before the 1970s,
more frequent indications for tracheostomy now include the management of respiratory
obstruction (e.g., severe subglottic stenosis) developing in the prolonged
intubated/ventilated premature infant, respiratory insufficiency due to neurologic
problems including head injuries, the management of excessive secretions, and
prevention of aspiration (Table 75.1). Children with Down syndrome have multiple
causes of upper airway obstruction (lymphoid tissue, tongue, shape and size of pharynx).
Elective tracheotomy should be considered along with adenotonsillectomy for severe
obstruction (6). A recent survey of 85 pediatric otolaryngologists representing over 2,000
tracheostomies per year indicated 40% were done for ventilator dependency, 30% for
extrathoracic obstruction, 20% for neurologic dysfunction, and 10% for intrathoracic
obstruction (7).

TABLE 75.1. INDICATIONS FOR
TRACHEOSTOMY



TRACHEOSTOMY VERSUS PROLONGED INTUBATION
In many cases, the choice between endotracheal intubation and tracheostomy is difficult.
Usually the nature of the problem, the expected duration of airway bypass or support, and
other medical issues affect the decision (4).
Endotracheal intubation can cause injury to the glottis, subglottic area, and trachea very
quickly. Edema, mucosal necrosis, and cartilage damage progress due to pressure of the
endotracheal tube. Perichondritis with local infection leads to delayed healing and fibrous
scar tissue. In adults, tracheostomy is usually recommended if intubation requirement is
greater than 2 weeks. The absolute time before injury is significant in the pediatric
population is hard to determine. Using an endotracheal tube with no cuff and careful tube
management with restricted movements on the tube add to the time that intubation may
be safe in the pediatric age group. Multiple self-extubations with repeated intubations
also may lead to earlier tracheostomy requirement (4).
Endotracheal tubes may become easily blocked due especially to the small lumen in
infants. With a tracheostomy, a shorter and larger tube can be placed with less dead space
and less damage to laryngeal and subglottic spaces. Intubation can be provided by a
variety of health care providers. Pediatric tracheotomy requires an experienced surgeon.
Tracheostomy is more comfortable for the patient. If the duration of intubation is
relatively short and the child is not moving a lot, intubation may be the choice.
Overall, tracheostomy is easier to manage, causes less damage to the larynx and trachea,
and may allow a child to be discharged from the hospital even if ventilation needs to be
continued, and this is certainly not possible with an endotracheal tube in place. Care for
the tracheostomy, changing of the tube, and replacing the tube in an emergency situation
are much more easily done by caretakers (including family) than is possible with an
endotracheal tube (4).
In special circumstances, the patient may undergo a single-stage laryngeal-tracheal
reconstruction rather than a tracheotomy. When a young child suffers from recurrent
croup or exertional dyspnea without asthma, one needs to be suspicious of a subglottic
lesion. If at endoscopy a noncritical stenosis is present, an alternative management option
for an otherwise healthy child is laryngeal-tracheal reconstruction rather than a
tracheotomy. Another scenario where one should consider an immediate laryngeal-
tracheal reconstruction is patients who are unable to be extubated and are found to have
subglottic stenosis at bronchoscopy. These patients must have good pulmonary function
otherwise a tracheotomy is indicated.
TECHNIQUE
Because of small anatomic structures, a short neck, and significant vital structures in the
immediate vicinity, performance of a tracheotomy in a child requires much more
attention to detail than one would expect in the adult patient. A planned tracheotomy
should be carried out under general anesthesia in the operating room over an endotracheal
tube or, in some cases, a bronchoscope. The child is placed on the table with a shoulder
roll to hyperextend the neck to bring the trachea more anterior and make palpation easier.
The head can be taped in this position, or the anesthesiologist may be able to extend the
head and hold that position during the procedure (Fig. 75.1). Careful palpation of the
neck is important as is marking of landmarks. The most prominent structure in the airway
will usually be the cricoid cartilage. This structure and the superior notch of the thyroid
cartilage and the sternal notch are marked with a marking pen. Esophageal feeding tubes
and stethoscopes should be removed so that inadvertent palpation of these structures is
not confused with the trachea itself. Local anesthesia with a vasoconstrictor, 1% lidocaine
with 1:100,000 epinephrine, is used to infiltrate the anterior neck area. The neck is then
prepared with a disinfectant solution such as povidone-iodine and the area draped out. It
is necessary for the anesthesiologist to have access to the face and the endotracheal tube
during the procedure. This area is best left undraped and careful attention carried out to
ensure a sterile field.

FIGURE 75.1. Positioning of the patient.



The skin incision (Fig. 75.2) may be made in either a transverse or vertical fashion
midway between the cricoid cartilage and the suprasternal notch. We prefer a vertical
incision because retraction is easier, it holds the tracheostomy tube better postoperatively,
and it does not cause sagging of the incision with the weight of the tracheostomy tube
later. Incision is carried through the skin, subcutaneous fat, and platysma muscle.
Hemostasis is obtained with electrocautery, and ligatures are used for larger vessels. The
strap muscles are retracted laterally (Fig. 75.3), and all dissection is performed in a
superior to inferior plane (Fig. 75.4). The assistant lifts the tissue with toothed forceps
and retracts with vein retractors. The thyroid isthmus may be retracted superiorly or
inferiorly as needed or divided if necessary. The isthmus is very small in infants and
usually can be divided with electrocautery. In older children, suture ligatures are carried
out in the usual fashion. When the trachea is identified, the cricoid cartilage is identified,
and the second and third tracheal rings are cleaned of soft tissue, providing good
exposure of the tracheal rings. Traction sutures are placed just lateral to the proposed
vertical tracheal incision before the incision to allow easy access to this area
postoperatively if inadvertent tube displacement occurs (Fig. 75.5). A vertical incision is
made through tracheal rings 2 and 3. At this point, the anesthesiologist will notice a loss
of positive pressure. As the endotracheal tube is withdrawn proximally, the tracheostomy
site is then retracted laterally with the traction sutures to provide easy placement of the
tracheostomy tube (Fig. 75.6). The endotracheal tube remains at the glottic level and
slightly into the subglottic space at this point to allow further ventilation through the
endotracheal tube if there is a problem with placement of the tracheostomy. A soft
suction catheter may be placed through the tracheostomy site before placement of the
tube to provide better visualization and to remove blood and secretions.

FIGURE 75.2. Anatomy of the neck and skin incisions.



FIGURE 75.3. Identification of the strap muscles and the
anterior jugular vein.



FIGURE 75.4. Dissection of the fascia in the midline.



FIGURE 75.5. Placement of a stay suture and incision of
the trachea.



FIGURE 75.6. Position of the tracheal tube.



Once the tube is in position, the area is inspected to be sure hemostasis is complete.
Tracheostomy ties are then secured, and the knot is tied laterally on either side of the
neck. A knot is tied and not a bow. In addition, it is best not to place this knot posteriorly,
because this may be confused sometimes with pajama ties. It is not advised to suture the
tracheostomy tube to the skin because if inadvertent displacement of the tube occurs
postoperatively, this delays the removal of the tube from the neck and immediate
replacement of the tube. The traction sutures are then labeled right and left with a 1-inch
piece of adhesive tape and then taped to the anterior chest wall to provide easy access and
prevent crossover and twisting of the sutures. The anesthesia circuit is connected to the
tracheostomy tube as soon as the tube is placed, and if ventilation is occurring adequately
still at this point, the endotracheal tube can be completely removed.
The choice of the tracheostomy tube depends on the expectant status of the child (8). If
the child is expected to be ventilated with positive pressures, a snug-fitting tube is
allowed at least in the beginning to prevent a leak, and a noncuffed tube is always
preferred. If the child does not require ventilation support, a smaller tube may be placed
to allow less pressure on the trachea and the allowance of air to pass around the trachea
and up to the vocal cords for phonation. The inner diameter of the tracheostomy tube,
however, should be adequate to provide adequate suctioning and air passage.
Laryngoscopy and bronchoscopy may be carried out at this point if the size and the
position of the tracheostomy tube are in question. The tracheostomy wound is not closed
because a complete seal leads to the possibility of subcutaneous emphysema
development. The child is then transferred to the pediatric intensive care unit for very
careful and specific tracheotomy care.
POSTOPERATIVE CARE
Hospital
Ventilator needs are generally ordered by the intensive care staff. Suctioning is carried
out every 1 to 2 hours and then as needed in the first few days as necessary for secretion
control. Necessary sedation and restraint are carried out so that the tracheostomy tube is
not dislodged or displaced during the first 5 to 7 days. A postoperative chest x-ray film is
taken in either the operating room or the intensive care unit to determine position of the
tube and especially the length of the tube with respect to the carina. If the child is not on
the ventilator, the child is generally able to take oral feedings the following day. The
tracheostomy ties are changed during the first week by the physician staff as needed for
cleanliness, and the first tracheostomy tube change is generally performed on
postoperative day 5 to 7. If the child is on a ventilator, the ventilator tubing should be
positioned in the midline of the chest or abdomen so that there is no side torque of the
tracheostomy tube, which would tend to displace the tube or lodge the lumen up against
the tracheal wall. After 5 to 7 days when a good tract is formed, the traction sutures are
removed, and the family or home caretakers begin to learn tracheostomy care,
troubleshooting of tracheostomy problems, and cardiopulmonary resuscitation and
arrange to prepare equipment at home for the eventual discharge from the hospital. In the
hospital, a team of a tracheotomy surgeon, nurse educator, respiratory therapist, speech
therapist, and occupational and physical therapist is frequently involved with the care of
the child.
Home
At home it is very important that a responsible adult is present at all times with a child
with a tracheostomy and able to resuscitate the child if a problem occurs. Tracheostomy
care manuals are available in most hospitals and are commercially available. At least one
tracheostomy manual is available that was written by the parent of a child with a
tracheostomy, making this very helpful for the families. In addition, a videotape about
tracheostomies and teaching with a tracheostomy doll are important techniques. When the
child is at home, it is important that all equipment is functioning, and it is advisable to
notify the electric company, telephone company, emergency teams, and the local police
that there is a child with a tracheostomy in the home. It is very important that the
electricity and telephone service to the house are maintained if an emergency arises. After
the child is discharged, the tracheostomy team usually will follow-up with the child on a
regular visit and also include the child's primary pediatrician for team care.
COMPLICATIONS
Complications of pediatric tracheostomies are typically broken down into intraoperative
complications, early postoperative complications, and late postoperative complications.
In a child less than 1 year of age, these have been reported as 3.3%, 13.3%, and 38.3%,
respectively (9). The overall mortality rate for this age group has been reported at 42%,
mostly reflecting the nature of the underlying disease process (9). The mortality rate for
the procedure itself has been reported at 1.6% (9). As expected, higher complications are
seen in premature infants and infants undergoing tracheotomy for upper airway
obstruction. On the other hand, the subglottic stenosis rate of occurrence has increased
from 2% in the 1970s to 23% in the 1980s, when prolonged endotracheal intubation in
neonates became popular (10).
Hemorrhage is the most common intraoperative complication (4). Careful limited
dissection on the trachea with meticulous control of bleeding will reduce this
complication. Significant persistent bleeding that is not controlled with electrocautery,
ligature ties, and loose packing with Gelfoam may indicate a coagulation abnormality.
Subcutaneous emphysema is a result of air trapping within the soft-tissue planes and can
be reduced by not suturing the skin incision and confining the dissection to the midline of
the trachea. Extensive subcutaneous emphysema is treated by enlarging the neck wound,
and occasionally a drain may need to be placed. Progression to pneumomediastinum and
pneumothorax may occur.
Pneumomediastinum and pneumothorax may occur from injury to the dome of the pleura
during the tracheotomy procedure. These may also occur by rupture of alveoli caused by
increased intrathoracic negative pressure. Excessive coughing may also cause this
problem. Minimal dissection can decrease this complication. A chest x-ray film done in
the recovery room to determine tube position can be used to detect air in these spaces. A
large pneumothorax may require chest tube placement.
Esophageal injury or tracheoesophageal fistula can also be avoided by careful meticulous
midline dissection and avoiding feeding tubes and esophageal stethoscopes during the
tracheotomy procedure. The incision into the anterior trachea wall could be carried too
deep, causing damage to the posterior trachea and the party wall separating the trachea
and esophagus. Injury to the recurrent laryngeal nerve can be avoided by midline
dissection and a midline vertical tracheal incision.
Tracheostomy tube plugging is the most common early postoperative complication and is
generally avoided by adequate suctioning and humidification (9).
Early postoperative complications can include accidental decannulation. Tracheostomy
ties should be carefully secured to avoid this complication. If this occurs in the first few
days before the tract is well formed, the traction sutures will help in replacement of the
tube. All caregivers of the child should be taught how to appropriately extend the neck
and replace the tracheostomy tube if accidental decannulation occurs. It is a good idea to
have an extra tube of the same size and one size smaller at the bedside for emergency
needs. In addition, if the tracheostomy tube cannot be replaced, an appropriately sized
endotracheal tube may be placed through the tracheostomy stoma. A plan of action
posted at the bedside should indicate whether this child can be resuscitated through the
larynx and upper trachea if the tracheostomy tube cannot be replaced. This would
indicate to the caregivers that bag-to-mouth or endotracheal intubation from above is
possible in these patients. Obstructive laryngeal and upper tracheal problems of course
could not be managed in this manner, and that also should be posted at the bedside. The
use of a soft clear suction catheter may assist in locating the tracheal opening and the
tracheostomy tube, or the endotracheal tube may be passed over the suction catheter.
Tracheitis and stoma infections can be treated with local care, careful suctioning as
needed, and adequate humidification. Cultures are usually done only if local routine
measures are not effective.
In neonates especially, the soft tracheostomy tube may work its way up against the
tracheal wall due to position changes and may temporarily obstruct the airway. Therefore,
it is important that the nursing team understand that head position and body position may
affect the patency of the airway. Late complications include accidental decannulation,
tube plugging, tracheitis, and tracheal stoma infections. In addition, some complications
are increased by the absolute duration of the tracheostomy tube requirement. Tracheal
wall erosion can occur from tracheostomy tube pressure on the anterior tracheal wall. The
innominate artery crosses anterior to the trachea at the superior thoracic inlet, and the
tube may erode that area. Cuffed tubes are usually not used in children, but they also can
cause erosion of the trachea wall. A low-lying tracheostomy below the third ring may
predispose to this problem. The tracheostomy tube that is too large may also add to this
problem. If there is any question at the time of the tube placement, laryngoscopy and
bronchoscopy can evaluate the relative size of the trachea lumen and the tube size. Any
bleeding from the tracheostomy may indicate a potential major problem. This usually
represents mild inflammation of the trachea from either drying or suction trauma, but
direct visualization to identify the bleeding source is required. This may be done through
the tracheostomy tube itself or through the stoma with a flexible scope.
Depending on the indication for the tracheostomy and the condition of the child, formal
laryngoscopy/bronchoscopy examination should be performed every 6 to 9 months while
the tracheostomy is in place. This is especially important in children with neurologic and
spinal problems who have abnormal body position.
Delayed tracheoesophageal fistula can occur from posterior wall erosion. An indwelling
nasogastric tube may predispose to this problem.
Tracheal granulomas are very common in the anterior wall on the superior lip of the
tracheal stoma. These can be granulation tissue early on and then become a fibrous mass
and may be pedunculated or sessile. A tube that is too large and poor wound care may
predispose to this problem. If the granuloma is broad based and not causing obstruction,
observation may be adequate. If the granuloma is large or pedunculated, it is wise to
remove it before it obstructs the stoma during tracheostomy tube change. Removal is
usually done under direct vision with a bronchoscope in place, pushing the granuloma
into the stoma, where it can be retrieved and excised through the stoma by sharp
dissection.
Suprastomal collapse and tracheal stenosis at this same site may occur from tracheostomy
tube pressure with local chondritis and weakening of the cartilage rings with a resulting
collapse. A transverse tracheal incision may also add to this problem. Removal of a
cartilage window is ill advised in children, because it may cause this problem. If
suprastomal collapse makes decannulation difficult, reconstructive procedures may be
needed to correct this. Revision of the tracheostomy tract with suture support from the
collapsed anterior wall through the strap muscles may be sufficient or tracheal
reconstruction with cartilage grafts may be necessary. Young infants who require
prolonged tracheostomies are more prone to this problem.
Subglottic stenosis as a result of tracheotomy can be reduced by avoiding high
tracheotomies and meticulous tracheostomy care. Cricothyrotomies are ill advised in
children, because this complication may occur. Tracheostomy in a hypoxic unsedated
child whose condition has been worsening during the observation stage and is unable to
be emergently intubated is best avoided by an earlier planned tracheotomy.
Persistent tracheocutaneous fistulae have been reported as high as 20% to 40% (11,12).
The age at the tracheotomy and the duration of tracheostomy seem to be the significant
factors. As more tracheotomies are done for long-term needs, the need for longer
cannulation has increased, and this complication may be higher. After decannulation, if
the tracheocutaneous fistula persists longer than 6 to 12 months, the treatment consists of
excision of the fistulous tract with multilayer closure and a postoperative drain. This will
reduce the risk of subcutaneous emphysema. Another method that may be used is
reinsertion of a fresh tracheotomy with rapid decannulation over the next few days.
When tracheotomy is performed for obstructive airway papillomatosis, distal disease
often predates the tracheotomy and the adverse effect of the procedure may be overstated
in the literature (13).
TRACHEOSTOMY TUBES
The narrow lumen of a child's trachea and other obvious anatomic differences prompted
the development of plastic tracheostomy tubes for pediatric use rather than a small adult
metal tracheostomy tube. A soft pliable tube more easily conforms to the shape of the
infant's or child's trachea. Multiple lengths with various inner and outer diameters are
important for the age range and the developing child. A pediatric polyvinyl chloride
tracheostomy tube was introduced in 1965 by Aberdeen and was the beginning of the
development of more modern pediatric tracheostomy tubes. Polyvinyl chloride (Shiley
and Portex) and silastic tubes (Argyle and Bivona) are more pliable and tend to collect
less secretions. They do not have an inner cannula and, because of their increased
malleability, may allow easier accidental decannulation. The smaller tracheostomy tubes
generally have no cuff. Both the Shiley and Bivona tubes are available in pediatric
standard sizes and neonatal assorted sizes. The softer silicone tube may be especially
important in a child with spinal abnormalities with an abnormally shaped or deviated
trachea. Holinger and Jackson metal tracheostomy tubes have inner cannulas and may be
important in reconstructive procedures when a stent may be wired to the tracheostomy
tube. The inner cannula provides a method of cleaning the tube lumen with the
tracheostomy that is left in place for long periods of stenting. More conformity and
standardization to standard endotracheal tube size and numbering system have developed,
but further progress is needed.
DECANNULATION
Before decannulation, the original problem requiring the tracheostomy must be evaluated
and determined to be improved to the point that the tracheostomy is no longer necessary
(14). In addition, the airway should be studied endoscopically to be sure that no new
problems created by the tracheostomy itself have developed. Vocal cord function should
also be assessed. Suprastoma granulomas should be resolved. After these criteria have
been met, progressively smaller tracheostomy tubes are placed until the smallest tube for
practical purposes is in place and can be plugged for an adequate length of time to
determine if the child can breathe through the larynx. These pluggings are usually done
only in the daytime if the child is out of the hospital. Nighttime plugging is usually
carried out in a monitored hospital bed just before decannulation. Sleep studies are done
only if the situation indicates evaluation to be necessary. Central respiratory problems
would require this. Prolonged plugging for underlying chronic lung disease with marginal
airways may be necessary to document decannulation criteria. In small infants, even the
smallest tracheostomy tube may completely fill the trachea so that plugging is not
possible. Fenestrated tubes are generally not used even during the decannulation process,
because granulation tissue from the fenestration irritation is a common occurrence in
children. Once the tube is removed, a mild pressure dressing is applied, and the child is
monitored in the hospital 24 to 48 hours.
COMMUNICATION CONCERNS
Many tracheostomies now are long term and are in infants under 1 year of age. There is
generally no problem of speech development if a child can phonate around the tube. The
child's basic disease condition may also affect speech and language development, as may
hearing loss, chronic deprivation states, and developmental delays. Speech pathologists
can evaluate and function even in an intensive care unit setting to help with these
problems. If a child was speaking before tracheostomy, long-term cannulation may lead
to problems, and speech therapy is an important part of ongoing therapy. Use of a smaller
tube allowing air leakage up through the vocal cords is adequate for vocalization. A
fenestrated tube is very irritating to the tracheal wall and usually not recommended. A
one-way speaking valve (Passey-Muir) may be used to allow air to flow up through the
vocal cords with exhalation, and this requires a tube that does not fill the entire tracheal
lumen. Otherwise, the child can be taught to plug the tracheostomy tube opening with a
finger or chin for vocalization. Our experience has been that children will learn this
automatically if they have normal skills, but encouragement and training with the speech
pathologist is vital. Speech training during cannulation will maximize receptive language,
encourage nonvocal behavior, and reduce the frustrations of the child and the parent.
Oromotor functions also are best maintained and developed through speech training. A
child who is decannulated prelinguistically (less than 9 to 12 months) usually will begin
to speak appropriately without help and will have little if any expressive delay but may
have voice and breath support problems. This can be helped with proper speech therapy.
Those decannulated at ages 1 to 4 years may have significant expressive delay and need
specific therapy in addition to voice and breath support therapy (15).
SUMMARY
Even though the placement of the tracheostomy in a child is a very difficult decision
frequently for both the family and the physicians, this life-saving maneuver, with its
ability to avoid further complications in the airway, is well established. Meticulous
surgery, team care postoperatively, and adequate attention to details of care including
speech therapy should lead to a desired outcome. Children can attend school and function
in most situations with other children (except swimming) if the right attitude and team
care are available. Failure to attend to these details may lead to significant frustrations,
complications, and even a fatal outcome.

HIGHLIGHTS
In managing airway problems in children, the desired outcome
is a safe airway that alleviates or improves the problem, can be
managed in the given setting, and produces the lowest
morbidity and mortality.
Because management of the child with a tracheostomy requires
a multidiscipline group, development of a dedicated team is
desirable.
Although the words are frequently used interchangeably,
tracheotomy refers to the surgical procedure and the act of
providing an opening into the trachea, whereas tracheostomy
refers to the actual hole in the trachea and is used to describe
the tube that is placed in the hole.
The history of tracheostomy dates back to 2000 BC, and its
popularity has been influenced by the history of diseases and
their treatment developments (e.g., diphtheria and polio).
Recent surveys show most pediatric tracheostomies are done
for ventilator dependency.
The choice between endotracheal intubation and tracheotomy
may be influenced by a variety of factors, but the duration of
required incubation is usually the determining factor.
After a tracheostomy is in place, the general care of a
tracheostomy tube is easier and can be done by a greater
number of caretakers than is possible with intubation.
With very few emergency exceptions, pediatric tracheotomies
are best carried out in the operating room, under general
anesthesia, and over an endotracheal tube.
The skin incision for a pediatric tracheotomy is the surgeon's
choice. However, a vertical skin incision provides easier access
to the trachea, holds the tracheostomy tube better, and usually
produces an acceptable scar.
Traction sutures through the trachea are important in pediatric
tracheotomy to allow access to this area postoperatively if
inadvertent tube displacement occurs before development of a
satisfactory tract.
Initial postoperative care in an intensive care unit setting,
adequate sedation, and meticulous tube care are especially
important in the first few days postoperatively.
Tracheostomy care should be effectively taught to the parents
and other caretakers to avoid apprehension and morbidity.
Before decannulation considerations, careful assessment of
vocal cord function, satisfaction that the original problem has
resolved, and evaluation for new tracheostomy-related
problems should be carried out.
A very important member of the tracheostomy team is a
qualified speech pathologist who will work with the child on
vocal skills, oromotor functions, and breath support.
CHAPTER REFERENCES
1. Frost EAM. Tracing the tracheostomy. Ann Otol 1976;85:618621.
2. Goodal EW. The story of tracheotomy. Br J Child Dis 1934;31:167170.
3. Myer C, Cotton R, Shott S. The pediatric airway: an interdisciplinary approach. Philadelphia:
J.B. Lippincott, 1995:151169.
4. Myers E, Stool S, Johnson J. Tracheotomy. New York: Churchill Livingstone, 1985:311.
5. Stool S. Tracheotomy and/or intubation. In: Healy G, ed. Common problems in pediatric
otolaryngology. Chicago: Year Book, 1990:423429.
6. Jacobs IN, Gray RF, Todd NW. Upper airway obstruction in children with Down syndrome. Arch
Otol Head Neck Surg 1996;122:945950.
7. Wooley A, Muntz H, Prater D. Physician survey on care of children with tracheotomies. Am J
Otolaryngol 1996;17:5053.
8. Casselbrant M. Tracheostomy. In: Bluestone CD, Stool S, eds. Atlas of pediatric otolaryngology.
Philadelphia: W.B. Saunders, 1995:448454.
9. Gianoli G, Miller R, Guarisco J. Tracheotomy in the first year of life. Ann Otol Rhinol Laryngol
1990;99:896900.
10. Arcand P, Granger J. Pediatric tracheostomies: changing trends. J Otolaryngol 1988;17:121126.
11. Wetmore R, Handler S, Potsic W. Pediatric tracheostomy: experiences during the past decade. Ann
Otol Rhinol Laryngol 1982;91:628631.
12. Joseph H, Jani P, Preece J. Pediatric tracheostomy: persistent tracheocutaneous fistula. Int J
Pediatr Otorhinolaryngol 1991;22:231234.
13. Shapiro AM, Rimmel FL, Shoemaker D, et al. Tracheotomy in children with juvenile-onset
recurrent respiratory papillomatosis: the Children's Hospital of Pittsburgh experience. Ann Rhinol
Laryngol 1996;105:15.
14. Benjamin B, Curley J. Infant tracheotomy: endoscopy and decannulation. Int J Pediatr
Otorhinolaryngol 1990;20:113118.
15. Simon B, Fowler S, Handler S, et al. Communication development in young children with long
term tracheostomies. Int J Pediatr Otorhinolaryngol 1983;6:3741.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

76 CAUSTIC INGESTION AND FOREIGN BODIES IN THE AERODIGESTIVE TRACT
Head & Neck SurgeryOtolaryngology
76




CAUSTIC INGESTION AND FOREIGN BODIES IN
THE AERODIGESTIVE TRACT
ELLEN M. FRIEDMAN

E.M. Friedman: Department of Pediatric Otolaryngology, Texas Children's Hospital, Houston, Texas.


Caustic Esophageal Injuries
Clinical Presentation
Treatment
Complications
Aerodigestive Foreign Bodies
Workup
Chapter References
CAUSTIC ESOPHAGEAL INJURIES
The mortality from caustic esophageal burns has decreased over the last 100 years as the
management of their sequelae has improved. In the last century, chronic esophageal
strictures alone accounted for a mortality rate of more than 40%, and management of the
unvisualized esophageal burns usually centered on crude supportive care (1). In this
century, diagnostic imaging and endoscopy have provided a basis for earlier appropriate
medical intervention, the development of safer stricture dilatation, and esophageal
reconstruction. Current mortality rates are between 0% and 20%, with most deaths caused
by only the most severe transmural burns.
Otolaryngologists have always been in the forefront of the diagnosis and management of
caustic ingestion. In 1927, Dr. Chevalier Jackson was successful in lobbying for special
labeling of caustic agents. His campaign to label dangerous substances resulted in
prominent printing of Poison on caustic agents, heralding an increased awareness in
handling and storing of certain products (2). Other legislative initiatives have also
benefited the public. These rulings have mandated lower concentrations of certain agents
for the retail consumption. The Safe Packaging Act has made bottles more difficult for
children to open (3). These modifications and increased public awareness have
significantly decreased the impact of caustic ingestions. Additionally, the change from
solid lye to liquid lye and liquid detergents has significantly changed patterns of the
epidemiology of caustic ingestions (4). The availability of the fluid form of caustic agents
has increased the amount of mucosa that could be injured with one swallow versus the
previous finding of more localized damage associated with the solid ingestions that
adhered to the mucosa.
The most common agents responsible for caustic ingestions fall into the following three
categories:
1. Caustic agents or alkali (pH greater than 7), for example, lime, laundry detergents,
and Clinitest tablets;
2. Corrosives or acids (pH less than 7), for example, toilet bowl cleaner, battery
fluid, and sulfuric acid;
3. Bleaches (pH approximately 7), for example, sodium hypochlorite.
These categories cause three distinct histologic reactions when they come into contact
with the oral, esophageal, and gastric mucosa. The caustic agents cause liquefaction
necrosis, which causes early disintegration of the mucosa with deep penetration into
tissues. This is reflected in the finding of more oral and upper esophageal involvement
with lye burns. The corrosive agents result in coagulation necrosis, which causes a
coagulum to form on the mucosa, thereby limiting deeper absorption until the agent
reaches the stomach, where the acidic pH can heighten the injury. This explains the
higher incidence of gastric complications such as gastric perforation and gastric stricture
formation associated with acid ingestions (Fig. 76.1). Furthermore, the severely
unpleasant taste of acid agents frequently causes early gagging, choking, and sputtering.
This may result in chemical epiglottitis as the acid agent comes into contact with the
mucosa of the epiglottis (Fig. 76.2). When this occurs, the rapid establishment of an
artificial airway is crucial, although there is no consensus regarding the superiority of
either endotracheal intubation or tracheotomy. This most likely should be determined by
the clinical situation and setting. Bleaches are of essentially neutral pH and are
considered esophageal irritants. Large series of patients with bleach ingestions have
shown no significant morbidity or mortality or associated complications. For this reason,
extensive workup of patients with bleach ingestions is not warranted (5).

FIGURE 76.1. This barium swallow after an acidic
ingestion reveals the enhanced effect of the corrosive
agent in the stomach, before gastric perforation.



FIGURE 76.2. Acidic agents more commonly result in
epiglottic inflammation or chemical epiglottitis.



The increasing appearance of small appliances and instruments in the household that use
disk batteries has resulted in an increase in the number of these aspirations (6). Disk
batteries may cause mucosal damage as early as 1 hour after ingestion. The liquid
contained within the disk battery is of extremely high alkaline pH and has leaked
following ingestion. The leakage can result in severe esophageal injury. Subsequent
esophageal perforations, stricture formation, and death have been associated with these
ingestions. Complications are minimized by rapid removal of the disk battery from the
esophagus. If the battery has passed into the stomach in an asymptomatic patient, most
likely the battery will pass into the stool. If the battery does not pass after 48 hours,
endoscopic removal is suggested.
The amount and type of agent ingested, the presence of other food in the stomach, the
gastrointestinal transient time, and the presence of gastroesophageal reflux will determine
the severity of injury. The initial contact of the agent will produce immediate changes in
the mucosa, which progress during the next 3 days. After the acute phase of the injury, a
latent period begins, during which time stricture formation may occur. The process may
proceed as rapidly as 1 month or during a period of years.
Superficial mucosal burns heal without sequelae. Burns deep enough to disrupt the
submucosa and muscular layer are complicated by a significant loss of mucosa. An
intense inflammatory response develops in the burned area with accompanying
esophageal dysmotility, and granulation tissue with fibroblasts brings a matrix of
collagen fibers to the newly formed connective tissue. The collagen fibers begin to
contract 3 or 4 weeks after the initial insult, and the irregular formation of this collagen
matrix enables adhesive bands to form. Pseudodiverticula form between these adhesions
as the contracting process continues. Stricture formation continues in the esophageal
lumen until a dense fibrous scar replaces the submucosal and muscular layers. In general,
only circumferential burns lead to esophageal strictures severe enough to cause clinically
significant morbidity.
Clinical Presentation
Most childhood ingestions occur in patients less than 5 years of age and frequently during
an unsupervised period. This may severely limit the physician's ability to obtain an
accurate history. Information concerning the quantity and type of agent may be
unavailable; however, if a parent brings a container of the suspected agent to the
emergency department or to the physician's office, it could be most helpful.
Early consultation with the poison control center is useful. Many states have a regional
poison control center hotline, which provides 24-hour-a-day telephone access for help in
the management of these challenging cases. The poison control center may be able to
identify the specific preparation and can make specific treatment recommendations.
The prognostic significance of clinical signs and symptoms has been the topic of many
articles in the literature (7,8). It appears that most signs, symptoms, and laboratory tests,
including complete blood count, sedimentation rate, and temperature, are not consistently
predictive of the gastroesophageal involvement.
Even the physical examination may not be useful in the prediction of esophageal injury.
It is critical to remember that the presence or absence of oral injuries (e.g., lip or buccal
burns) cannot accurately predict the presence or absence of more distal involvement.
Approximately 20% of patients without visible oral lesions have been shown to have
significant esophageal damage (9). Interestingly, 70% of patients in some series have had
oropharyngeal burns without associated esophageal injury (10) (Fig. 76.3). Therefore, the
absence or presence of visible injury on physical examination should not influence
further investigation. In contrast, certain indicators of severe injury, such as
thoracoabdominal pain or tachycardia with hypotension, can be correlated reliably with a
significant injury. Dysphagia, retrosternal pain, or abdominal pain often indicates severe
esophageal injuries. Hoarseness or stridor forewarns of progressive airway obstruction
from supraglottic or glottic edema or tracheal injury.

FIGURE 76.3. The presence or absence of lip burns after
a caustic ingestion cannot reliably predict the possibility
of esophageal involvement.



Treatment
Most caustic agents have instructions for treating the accidental ingestion on the
packaging. Unfortunately, much of this information has been shown to be erroneous. The
use of neutralizing agents such as vinegar for lye ingestion and sodium bicarbonates to
neutralize acid ingestions may cause exothermic chemical reactions that will further
increase the injury to the esophagus. Using an acid (e.g., citrus juices) to neutralize a base
has been condemned, although recent calculation shows that volume and blood flow
dissipate any heat produced by the exothermic reaction (11). Current recommendations
therefore call for the judicious use of diluting agents such as water or milk to remove the
agent from the esophagus. A child who has ingested a hazardous substance should drink
water or have the mouth thoroughly irrigated by water or milk (a neutral buffer) in large
volumes. Fluid intake should be no more than 15 mL/kg of weight, because excessive
fluids may induce vomiting (12). Gastric lavage and induced vomiting with emetics (i.e.,
ipecac) are contraindicated. Vomiting will cause repeated exposure of the agent to the
esophageal mucosa and thereby increase the risk of injury. Other emergency department
interventions such as gastric lavage should be avoided because the blind passage of a
nasal gastric tube increases the risk of iatrogenic esophageal perforation. The role of
antacids has not been fully evaluated but bears further investigation.
Because the history may be inadequate and the physical examination inconclusive, direct
visualization by endoscopy is the most reliable and accurate method to determine the
extent of esophageal injury. The timing of endoscopy is crucial (13,14). If the
examination is performed earlier than 12 hours after the ingestion, adequate time may not
have passed for the injury to fully manifest, and therefore the examination may
underestimate the damage. Delayed examination during the period of structural weakness
of the esophageal wall will increase the risk of iatrogenic injury during the examination.
Therefore, endoscopy should be performed between 24 and 48 hours after the ingestion to
achieve the highest degree of patient safety and to yield the most information.
If patient referral is delayed beyond 48 hours, endoscopy should be avoided. In this case
barium swallow, although not as revealing or reliable as endoscopy, may be used as an
initial assessment. Radiographic techniques using contrast media for studying acute
injuries may be inaccurate, with 30% to 90% false-negative rates reported in patients with
moderate esophageal involvement. However, severe esophageal injury has been
accurately depicted by the radiographic demonstration of atony and poor distensibility as
early as the day of initial injury (15). These conflicting findings highlight the value of
direct endoscopic visualization of the esophagus and stomach as the most valid method of
establishing the degree of injury. The most useful role of the barium swallow is to verify
perforation or evaluate progressive dysphagia due to stricture formation. In children in
whom low suspicion of an actual ingestion exists, hospitalization and conservative
observation can be followed. A barium swallow may also be useful in these cases.
Endoscopy is used to determine the esophageal damage and will establish a precise
diagnosis, allowing for rational therapy. On endoscopy, grade 1 is a superficial injury,
grade 2 is transmucosal, and grade 3 is transmural. Notations should be made concerning
the presence of circumferential lesions as well. The grade of the injury and the degree of
involvement will determine which patients will benefit from pharmacologic intervention
and help the prognosis (Table 76.1).

TABLE 76.1. ENDOSCOPIC APPEARANCE OF
ESOPHAGEAL BURNS



Steroid administration is aimed at decreasing stricture formation and has been shown to
be most effective in the transmucosal (grade 2) injuries. The superficial burns (grade 1)
do not frequently progress to stricture formation or other complications and therefore do
not warrant steroid therapy. The transmural burns (grade 3) will require surgical
intervention and may actually be hampered by steroid treatment. Therefore, steroids are
contraindicated in these severe injuries. The endoscopic findings are crucial to identify
the appropriate patients who will benefit from the early initiation of steroid therapy and
eliminate those in whom steroids are not necessary or are actually harmful.
The appropriate steroid dosage remains controversial. No controlled reports adequately
demonstrate the proper dosage. Reports of the clinical efficacy of steroids have been
conflicting. Different methods of reporting the initial injury, the schedule and dose of
steroids used, and the variability of experience with severe burns have made a consensus
impossible (16,17 and 18). Current recommendations are from 1 to 2 mg/kg/day of
prednisone to a maximum dosage of 60 mg/day. This dosage is continued for a 21-day
period on a tapered regimen.
The use of prophylactic antibiotics is also controversial (19,20). In reviewing the
literature, mounting evidence suggests that antibiotics do not decrease the incidence of
stricture formation or other complications. It is our current recommendation to withhold
antibiotics until the patient develops signs or symptoms of a secondary infection.
Lathyrogenic agents that reduce collagen cross-bonding have also been used to decrease
esophageal strictures. Lathyrogens such as -aminopropionitrile, acetylcysteine, and
penicillamine have decreased the formation of laryngeal strictures from alkali injury (21).
Although systemic toxicity has been a limiting factor in the clinical use of these agents,
continued work with better tolerated drugs (e.g., penicillamine) may prove useful.
Protection of the injured esophageal wall from the effects of gastric acid may prove to be
extremely important in decreasing granulation tissue and subsequent scar formation.
Sucralfate therapy for lye and acid burns has shown promise in the healing of esophageal
ulcers without stricture formation. As with steroid therapy, success with this regimen may
be greatest in the patient with midrange second-degree burns. The sucralfate must be
given orally as a liquid slurry of its tablet form, which may limit its use in the more
severe injuries. Future clinical and laboratory studies with liquid antacids, H
2
blockers,
and omeprazole may yield other important forms of therapy.
Patients who have sustained moderate to severe esophageal injury and survive the acute
phase usually have a varying degree of damage. Stricture formation with possibly long
segments of involvement and esophageal atony may result. Since the 1920s, esophageal
dilatation has been used to improve the esophageal lumen. Strictures may form in
multiple locations or vary in length or severity, requiring antegrade dilatation or periodic
swallowing of mercury-filled dilators. Long-term management involves repeated
hospitalizations for serial dilations with difficulties maintaining adequate nutritional
status and chronic anemia. These sequelae can be debilitating.
Mechanical stenting has been recommended to avoid stricture formation in selected
patients with second- and third-degree esophageal injuries. It is unclear if this technique
has actually improved the long-term outcome of these patients.
A major change in the management in caustic ingestions has been the growing interest in
early surgical resection of the damaged esophagus or stomach with reconstruction
(22,23). Certain centers have aggressively approached this issue and recommend early
surgery. The indications for surgery and a favored surgical approach, however, remain
controversial. Patients with grade 1 burns must never undergo surgical repairs because
such a low risk of complication exists without treatment. Most likely, patients with grade
3 burns do actually benefit from early aggressive surgical intervention. The patient with
grade 2 involvement, however, requires thoughtful consideration before embarking on a
surgical route because only a low percentage appears to proceed to further complications.
Colon interposition is a surgical procedure with significant risk, including the possibility
of long-term postoperative dysmotility. This procedure may not provide any advantage
over the risk of potential stricture formation. These decisions must be made on an
individual basis, considering many factors, including regional experience and available
medical facilities.
Complications
The most common complication after caustic ingestion is stricture formation. Strictures
may be mild and cause only slight alterations of diet or may be severely debilitating (Fig.
76.4) Other complications, including esophageal perforation, tracheoesophageal fistula,
gastric perforation, mediastinitis, peritonitis, pneumonia, sepsis, and death, also occur.
The late development of hiatal hernia, reflux esophagitis, peptic stricture, or esophageal
cancer 25 to 69 years after injury makes esophagectomy and reconstruction a reasonable
alternative to long-term stricture dilatation. The association of esophageal carcinoma in
patients who experienced an earlier caustic ingestion is most interesting. This form of
esophageal carcinoma is unusual in that an equal male-to-female ratio of occurrence
exists and a younger age group than expected is usually affected. In a large series of
esophageal carcinomas, a 1% to 4% incidence of caustic ingestion was found in the
clinical histories (24). Although the exact degree of increased risk for carcinoma is
unknown, it has been estimated to be 1,000-fold. Fortunately, because these carcinomas
typically develop in scar tissue, their tendency for distant metastasis is lower, and
potential cure with resection is higher. For this reason alone, long-term follow-up of
patients with esophageal stricture is warranted, regardless of their symptoms. Any patient
who develops dysphagia years after a caustic injury should undergo radiologic evaluation
and esophagoscopy.

FIGURE 76.4. Esophageal stricture formation after
caustic ingestion may occur slowly over years. This
stricture developed within 1 month of a lye ingestion.



AERODIGESTIVE FOREIGN BODIES
Foreign-body accidents occur in two basic forms: foreign-body aspiration, where the
object is lodged in the laryngotracheobronchial axis, and foreign-body ingestion, where
the object is located in the esophagus. Both forms have many similarities, including
significant associated morbidity and mortality.
In the United States, over the last quarter century the incidence of foreign-body aspiration
has not changed significantly and is unlikely to do so as long as children continue to put
objects in their mouths to explore their surroundings. There has been a dramatic decrease
in childhood deaths from asphyxiation by ingested objects, accounting for approximately
3,000 deaths per year (25). The associated morbidity in survivors of prolonged
asphyxiation is considerable.
The most common age group affected are toddlers between 2 and 4 years of age. Case
series from the last decade reflect that children younger than 5 years of age account for
approximately 84% of cases, and children younger than 3 years of age account for 73%
(26). The high incidence in this age group reflects the oral tendency of these children, and
in addition, children this age do not have a full posterior dentition or mature
neuromuscular mechanisms for appropriate swallowing and airway protection. Boys are
affected more frequently than girls in a ratio of approximately 2:1. The acute episode is
heralded by gagging and choking and is quite obvious. Because toddlers may be out of
parents' view during the acute episode, the period of acute distress may not be witnessed
by an adult, making it more difficult to be sure of the diagnosis. As the foreign body goes
down the tracheobronchial axis, the active distress subsides. When the foreign body lands
in its final resting place, the symptoms may vary in severity depending on the object's
size, the degree of obstruction, and surrounding tissue reactions.
Up to 50% of patients with foreign-body aspirations do not have a contributing history
available. When a patient is seen with nonspecific pulmonary complaints such as
intermittent coughing or wheezing, the differential diagnosis is long. Without a high
degree of suspicion of foreign-body aspiration, physicians may proceed with allergy
testing, initiation of asthma therapy, or treatment for various infections or search for a yet
more exotic diagnosis while overlooking one of the most common etiologies. It is not
uncommon for a patient to be treated for several months, including repeated
hospitalizations for various erroneous ailments, before proceeding with bronchoscopy to
establish a correct diagnosis and the removal of a retained foreign body. Therefore, any
patient with a prolonged nonspecific pulmonary complaint, even without the history of
acute aspiration, should raise the question of a retained foreign body. It is not surprising
that a review by Cohen et al. (27) of 143 cases of foreign-body aspirations in children
indicated that only 41% were seen by a physician on the first day after the initial episode.
Reilly et al. (28) noted that 85% of pediatric aerodigestive foreign-body injuries were
diagnosed on the first physician visit and that foreign-body aspirations were seven times
more likely to have a delay in diagnosis than foreign-body ingestions.
The most common objects aspirated by children are food products. Most are peanuts, but
raisins, seeds, and other nuts are common as well. Beans and seeds absorb water over
time and with subsequent swelling will rapidly result in a complete bronchial obstruction.
Other organic foreign bodies also cause increased surrounding tissue reaction, and this
may result in a condition known as arachidonic bronchitis, which is seen radiographically
as a spidery pattern on chest radiograph. Inert foreign bodies are less reactive and may
remain in one position for a long period without causing increasing obstruction. The most
common inert bronchial foreign bodies are pieces of toys. In the past, plastic toy pieces
have been nonradiopaque and therefore undetectable on plain chest radiographs. Several
companies (e.g., the 3M Company and Mattel Company) have sponsored research and
development that have resulted in the invention of a radiopaque plastic; however, this
plastic has not been put into frequent commercial use. The aspiration of latex balloons
has a high morbidity and mortality and has prompted the move toward Mylar balloons for
children.
McGuirt et al. (29) found that the elderly also had a significant incidence of foreign-body
aspiration, which is perhaps due to their lack of dentition or to suppressed reflexes after
alcohol intake. The foreign body most commonly aspirated by adults includes food
products or portions of dental prosthesis.
Workup
Chest auscultation most commonly will reveal decreased breath signs on the obstructed
side with wheezing and decreased localized air entry. The chest findings are frequently
misinterpreted as asthma or pneumonia. In view of prolonged or unusual symptoms
without clinical response to routine pharmacologic management, bronchoscopy should
not be delayed.
Although the most important noninvasive study investigating foreign bodies is the
radiographic search for signs of obstruction, Strome (30) showed that 25% of plain chest
radiographs of patients with foreign bodies are within normal limits. This may be due to
the fact that the hallmark radiographic signs associated with foreign-body aspiration are
most readily demonstrated by an expiratory plain film or on fluoroscopy. Plain chest
films on inspiration will not demonstrate the classic findings because only on expiration
will one see the mediastinal shift and air trapping (Fig. 76.5). Therefore, use of expiratory
film or fluoroscopy will increase the likelihood of establishing the correct diagnosis
radiographically. When fluoroscopy is not available, right and left lateral decubitus films
may demonstrate the pathology. Physiologically in the normal unobstructed lung on
lateral decubitus chest radiograph, the lung will be deflated in the down position. If the
down lung in the decubitus film remains fully aerated, obstruction exists, indicating the
presence of a foreign body. Although these radiographic techniques are useful in
establishing a diagnosis, approximately 10% of cases with foreign-body aspiration will
have negative fluoroscopy. Therefore, even with negative fluoroscopy, a patient with a
suspicious clinical history should still be considered for bronchoscopic evaluation.

FIGURE 76.5. Foreign-body chest x-ray film.



Bronchoscopy must be performed by an experienced team that includes an
anesthesiologist, endoscopist, and nurse. Retrieval of a foreign body in a child involves
excellent communication among the members of the team to ensure that a bad situation
does not become worse. Partial airway obstruction can rapidly become complete without
an experienced coordinated approach. Care must be exercised to remove the foreign body
smoothly and efficiently without impacting the foreign body more distally or fragmenting
the object.
The major advance in the retrieval of foreign bodies involves improvements in the
delivery and types of agents used for anesthesia and the improvements in instruments
available for the endoscopist. Magnification and the wide variety of available forceps
have enhanced the retrieval of foreign bodies even in the smallest of children.
Bronchoscopy should not be attempted without a full range of age-appropriate sized
instruments available. The endoscopist should personally check the equipment before
beginning the procedure. The endoscopist must remember that complete endoscopy is
necessary to rule out the possibility of multiple foreign bodies, which is not an
uncommon occurrence. After removal of one foreign body, the endoscope is reintroduced
into the trachea to search for additional foreign bodies and to assess any trauma to the
tracheal mucosa. The incidence of a second foreign body in the airway is 5% (29).
The removal of a retained foreign body presents another set of difficulties. The possibility
of granulation tissue and postobstruction infection exists. Removal may be hampered by
poor visualization associated with swelling, granulation, or bleeding. These added
challenges further reinforce the need for an earlier examination, when the removal of a
foreign body will be less difficult. Postinstrumentation edema may result, which will
usually respond to intravenous steroids and inhaled vaponephrine treatments. Postural
drainage should be avoided because it is uncommon for this to result in the successful
removal of a foreign body and more likely may dislodge the foreign body to another
more distal location.
Esophageal foreign bodies deserve special comment. It is estimated that approximately
1,500 people die annually from complications related to foreign-body ingestion, with
children being the most common victims (31). Esophageal foreign bodies frequently
present with a mild to moderate degree of respiratory distress. This finding is secondary
to the extreme compliance of the party wall between the esophagus and the trachea. The
mass effect of an impacted object in the esophagus therefore will have a significant
impact on the airway. Figure 76.6 reveals a patient seen in the emergency department in
severe respiratory distress who underwent an emergency tracheotomy. On postoperative
chest x-ray film, the source of the airway obstruction was found to be an esophageal
foreign body. Interestingly, dysphagia or drooling may be a late symptom associated with
an esophageal foreign body.

FIGURE 76.6. An emergency tracheotomy was
performed in this patient to relieve the severe airway
distress due to an unsuspected esophageal foreign body.



The most common esophageal foreign bodies, coins, are readily seen on radiographic
examination. The most common foreign body resulting in a fatality is a portion of
undigested hot dog lodged in the esophagus that impacts the airway and can cause
complete airway obstruction.
The most common location for an esophageal foreign body to lodge is at the normal
anatomic narrowing of the esophagusmost frequently at C-6 or the level of the
cricopharyngeal muscle. If a foreign body lodges at another area, the possibility of an
abnormal underlying narrowing such as congenital esophageal stricture should be
investigated.
The safest method for the retrieval of an esophageal foreign body is under general
anesthesia with a protected airway. The removal of an esophageal foreign body under
fluoroscopy in the radiology suite with the use of a balloon catheter can be dangerous.
Although dislodging a foreign body from the esophagus into the larynx, resulting in
airway obstruction, is an uncommon occurrence, it does not seem to be a warranted risk
when a safe, tried, and true alternative is readily available.
An interesting finding concerning caustic ingestions and foreign-body aspirations has
emerged. In certain cases, the possibility of intentional child abuse should be investigated
(32,33 and 34). Negligence, or an act of omission, may result in an accident, yet this may
be the sign of a troubled family and a child at risk. Intentional abuse, or an act of
commission, is more worrisome. There have been an increasing number of cases reported
demonstrating child abuse or Munchausen syndrome by proxy with foreign-body or
caustic ingestion. Some cases are obvious; others are more difficult to recognize.
Increased vigilance will aid and protect the children at risk. Most states mandate the
reporting of suspicious episodes.
The best approach to caustic ingestion and foreign-body aspiration or ingestion is
prevention. Prevention can be approached in two ways: legal commercial modifications
and increased public awareness.
Many measures have been undertaken by both the government and the private sector that
have improved public safety. Public education campaigns are to be commended. Early
diagnosis and improved management have resulted in favorable outcomes. Although this
result is encouraging, prevention must remain the goal.

HIGHLIGHTS
Alkali substances (pH greater than 7) cause liquefaction
necrosis with the early disintegration of mucosa and deeper
penetration. Acidic substances (pH less than 7) cause
coagulation necrosis, which limits deeper absorption in the
upper esophagus.
Bleach is only an esophageal irritant and is highly unlikely to
result in a significant injury; therefore, bleach ingestions do not
require a full workup.
There is no reliable relationship among the signs, symptoms,
physical examination, and the degree of injury except when
dysphagia, retrosternal pain, or abdominal pain is present,
indicating severe injury.
Endoscopy is critical to assess esophageal involvement and
should be performed between 24 and 48 hours after injury,
allowing time for the injury to manifest itself and avoiding
instrumentation during the period of esophageal wall weakness.
Endoscopy will help identify the patients with second-degree
esophageal injuries who will benefit from oral steroids.
A foreign body in the aerodigestive tract frequently presents
with an unwitnessed episode; therefore, the diagnosis should be
considered in any patient with prolonged or unusual pulmonary
symptoms.
Expiratory films or chest fluoroscopy is diagnostic in most
cases, revealing hyperaeration of the obstructed lung and shift
of the mediastinum.
An esophageal foreign body in young children frequently
presents with respiratory distress rather than dysphagia, which
is a later symptom.
A foreign body in the aerodigestive tract should be removed
endoscopically; always look for a second foreign body or an
underlying anatomic abnormality.
CHAPTER REFERENCES
1. Thompson JN, Brown JD. Caustic ingestion and foreign bodies in the aerodigestive tract. In:
Bailey BJ, Johnson JT, Pillsbury HC, et al., eds. Head and neck surgery-otolaryngology.
Philadelphia: J.B. Lippincott, 1993:725731.
2. Clerf LH. Historical vignetteChevalier Jackson. Arch Otolaryngol 1966;83:124128.
3. Friedman EM. Caustic ingestion and foreign bodies in the aerodigestive tract. Pediatr Clin North
Am 1989;36:14031410.
4. Ashcroft K, Padula RT. The effect of dilute corrosives on the esophagus. Pediatrics 1974;53:226.
5. Schild JA. Caustic ingestion in adult patients. Laryngoscope 1985;95:11991201.
6. Moore WR. Caustic ingestions: pathophysiology, diagnosis, and treatment. Clin Pediatr
1986;25:192196.
7. Sugawa C, Mullins RJ, Lucas CE, et al. The value of early endoscopy following caustic ingestion.
Surg Gynecol Obstet 1981;153:553.
8. Friedman EM, Lovejoy FH. The emergency management of caustic ingestions. Emerg Med Clin
North Am 1984;2:7786.
9. Gaudreault P, Parent M, McGuigan MA, et al. Predictability of esophageal injury from signs and
symptoms: a study of caustic ingestion in 378 children. Pediatrics 1983;71:767.
10. Hawkins DB, Demeter MJ, Barnett TE. Caustic ingestion: controversies in management. A review
of 214 cases. Laryngoscope 1980;90:98109.
11. Gosselin RE. Clinical toxicology of commercial products. Baltimore: Williams & Wilkins,
1984;3:245.
12. Holinger LD. Esophageal injury and stricture. In: Holinger LD, Lusk RP, Green CG, eds.
Pediatric laryngology and bronchoesophagology. Philadelphia: Lippincott-Raven, 1997.
13. Sugawa C, Mullins RJ, Lucas CE, et al. The value of early endoscopy following caustic ingestion.
Surg Gynecol Obstet 1981;153:553.
14. Kaplan J, Gandhi K, Elsen J, et al. Early esophagoscopy for diagnosis of esophageal burns. Arch
Otolaryngol 1961;73:5253.
15. Chen YM, Ott DJ, Thompson JN, et al. Progressive roentgenographic appearance of caustic
esophagitis. South Med J 1988;81:724.
16. Cardona JC, Daly JF. Current management of corrosive esophagitis: an evaluation of results in
239 cases. Ann Otol Rhinol Laryngol 1971;80:521.
17. Anderson KD, Rouse TM, Randolph JG. A controlled trial of corticosteroids in children with
corrosive injury of the esophagus. N Engl J Med 1990;323:637640.
18. Krey H. On the treatment of corrosive lesions in the esophagus: an experimental study. Acta
Otolaryngol 1952;102[Suppl]:1.
19. Middlekamp JN, Cone AJ, Ogura JH, et al. Endoscopic diagnosis and steroid and antibiotic
therapy of acute lye burns of the esophagus. Laryngoscope 1961;71:13541362.
20. Webb WR, Koutras P, Ecker RR, et al. An evaluation of steroids and antibiotics in caustic burns
of the esophagus. Ann Thorac Surg 1970;9:95101.
21. Thompson JN. Corrosive esophageal injuries, II: An investigation of treatment methods and
histochemical analysis of esophageal strictures in a new animal model. Laryngoscope
1987;97:1191.
22. Reyes HM, Liu CY, Schlunk FF, et al. Experimental treatment of corrosive esophageal burn. J
Pediatr Surg 1974;9:317327.
23. Ritter FN, Gago O, Kirsh M, et al. The rationale of emergent esopharyngogastrectomy in the
treatment of liquid caustic burns of the esophagus and stomach. Arch Otolaryngol 1971;80:513
519.
24. Isolauri J, Markkula H. Lye ingestion and carcinoma of the esophagus. Acta Chir Scand
1989;155:269271.
25. Kramer TA, Reding KH, Salkeld LS. Tracheobronchial and esophageal foreign body in the
pediatric population. J Otolaryngol 1986;15:355.
26. Darrin DH, Holinger LD. Foreign body of the larynx, trachea and bronchi. In: Bluestone CD,
Stool S, Kenna MA, eds. Pediatric otolaryngology, 3rd ed. Philadelphia: W.B. Saunders,
1995:1390.
27. Cohen SR, Herbert WI, Lewis GB Jr, et al. Foreign bodies in the airway: five year retrospective
study with special reference to management. Ann Otol Rhinol Laryngol 1980;89:437445.
28. Reilly JS, Walter MA, Beste D, et al. Size/shape analysis of aerodigestive foreign bodies in
children: a multi-institutional study. Am J Otolaryngol 1995;16.
29. McGuirt WF, Holmes KD, Feehs R, et al. Tracheobronchial foreign bodies. Laryngoscope
1988;98:615.
30. Strome M. Tracheobronchial foreign bodies: an updated approach. Ann Otol Rhinol Laryngol
1977;86:649654.
31. Webb WA. Management of foreign bodies in the upper GI tract. Gastroenterology 1988;94:204.
32. Friedman EM. Caustic ingestion and foreign body aspiration: an overlooked form of child abuse.
Ann Otol Rhinol Laryngol 1987;6:709712.
33. Leavitt EB, Parcus RC, Bulkachevsky R. Otolaryngologic manifestations of child abuse. Arch
Otolaryngol Head Neck Surg 1992;118:629631.
34. Willging JP, Bower CM, Cotton RT. Physical abuse of children: a retrospective review and an
otolaryngology perspective. Arch Otol 1992;118:584590.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

77 CONGENITAL NECK MASSES AND CYSTS
Head & Neck SurgeryOtolaryngology
77




CONGENITAL NECK MASSES AND CYSTS
ROBERT L. PINCUS

R.L. Pincus: Department of Otolaryngology, New York Otolaryngology Group, New York, New York.


Lateral Neck Masses
Branchial Anomalies
Laryngoceles
Pseudotumor of Infancy
Midline Neck Masses
Thyroglossal Duct Cysts
Thymic Cysts
Dermoid Cysts
Plunging Ranulas
Teratomas of the Neck
Masses of Entire Neck
Lymphatic Malformations
Hemangiomas
Chapter References
Congenital masses are the most common noninflammatory neck masses in children.
Although usually present at birth, they can appear at any age. Each type of mass has a
typical presentation and location in the neck (Table 77.1).

TABLE 77.1. NECK MASSES BY LOCATION



LATERAL NECK MASSES
Branchial Anomalies
Branchial anomalies (BA) account for about 17% of pediatric neck masses (1). The
branchial apparatus was first described by Baer in 1827. Although somewhat
controversial, most experts now believe that lateral cervical cysts are branchiogenic in
origin (2). A branchial cyst is a tract with only an internal or external opening. Branchial
fistulae are open from the aerodigestive tract to the skin. Cysts are considered to be
entrapped remnants of branchial clefts or sinuses; sinuses (with or without cyst) are
remnants of clefts or pouches and fistulae results from the persistence of both cleft and
pouch. The course of each BA is caudal to the structures derived from its arch and dorsal
to the structures that develop from the following arch.
Understanding the presentation and course of BA requires knowledge of the embryology
of the branchial apparatus. Proper surgical planning is essential to avoid incomplete
excision of BA. Recurrence can occur in as many as 22% of patients who have had
previous surgery (2). The branchial apparatus begins to develop during the second week
of gestation. By the beginning of the fourth week, there are four well-defined pairs of
branchial arches, separated by branchial clefts. Each arch has an artery, cartilaginous bar,
muscles, and nerve (Table 77.2 and Fig. 77.1; see also Color Plate 23 following p. 370)
(3). First BA probably make up fewer than 1% of all BA. First BA usually appear on the
face or are related to the auricle. Work (4) described type I and type II anomalies. Type I
first BA contain only epidermoid elements without cartilage or adnexal structures. They
present as duplication anomalies of the external canal and may pass close to the facial
nerve. Type II first BA are more common. They contain both ectoderm and mesoderm
and may present in the neck (4). Type II anomalies typically present after infection as an
abscess below the angle of the mandible. These pass upward through the parotid gland,
passing lateral or medial to the facial nerve, and end inferior to the external auditory
canal or into the canal at the bony cartilaginous junction (5).

TABLE 77.2. EMBRYOLOGY OF NECK MASSES



FIGURE 77.1. Definitive structures formed by the
cartilaginous components of the various pharyngeal
arches. (See also Color Plate 23 following p. 370.) (From
Sadler TW. Langman's medical embryology, 8th ed.
Philadelphia: Lippincott Williams & Wilkins, 2000, with
permission.)


Second BA are the most common type. They can present as a cyst, sinus, or fistula. If the
membrane separating the second cleft and pouch breaks down, a complete fistulous tract
may persist. Sinus tracts may otherwise occur, opening internally or externally. Second
BA present anterior to the sternomastoid muscle. The tract passes deep to second arch
structures, including the external carotid artery and the stylohyoid and posterior belly of
gastric muscles, and superficial to structures of the third arch derivation, such as the
internal carotid artery. The tract ends in the tonsillar fossa.
Second branchial cysts present as painless fluctuant masses below the angle of the
mandible and anterior to the anterior border of the sternomastoid muscle (Fig. 77.2).
These can suddenly enlarge after an upper respiratory tract infection. Although
commonly presenting in children and young adults, branchial clefts cysts can first come
to clinical attention at any age. Treatment is by surgical excision.

FIGURE 77.2. Second branchial cyst.



Third branchial defects are rare. They present lower in the neck, also anterior to the
sternomastoid muscle. Third BA are deep to the third arch derivatives, such as the
glossopharyngeal nerve and the internal carotid artery, but superficial to structures of
fourth arch derivation, such as the vagus nerve. They enter the pharynx at the thyrohyoid
membrane or piriform sinus.
An anomaly of the fourth branchial arch was first reported by Sanborn (6) in 1972. Since
that time, more than 40 cases have been reported; all but 3 have been left-sided. Fourth-
arch defects arise from the apex of the piriform sinus and course inferior to the superior
laryngeal nerve. They may present as recurrent thyroiditis or recurrent lower neck
abscesses (7).
Elective surgical excision is the treatment of choice for all BA. Abscesses should first be
treated by incision and drainage. The cyst should then be removed with its tract traced to
its origin in the aerodigestive system. Inspection of the piriform sinus should precede
surgical exploration in third and fourth BA. Rosenfeld and Biller (8) recommended
removal of the posterior portion of the thyroid cartilage to gain adequate exposure to the
piriform sinus in excision of fourth BA. Armed with knowledge of the tract's pathway,
care must be taken to avoid damage to the neighboring neural and vascular structures. An
external approach is used, often with a stepladder incision. Recurrence is uncommon in
the previously unoperated noninfected neck (2).
Laryngoceles
External laryngoceles may present as cystic swellings anterior to the sternomastoid
muscle and are rare causes of respiratory distress in the newborn. A laryngocele is an air-
filled herniation of the saccule of the laryngeal ventricle. They are believed to be caused
by a prolonged increase in intraglottic pressure in patients with a predisposing long
sacculus. The most common symptoms of laryngoceles are cough, hoarseness, and a
foreign-body sensation. Internal laryngoceles are confined within the larynx and present
as cystic swellings of the aryepiglottic fold (Fig. 77.3). External laryngoceles extend
through the thyrohyoid membrane, come to lie lateral to the thyroid cartilage, and present
as lateral neck masses. Secondary infection of a laryngocele may cause a laryngopyocele,
which presents as a neck abscess. Surgery is recommended for symptomatic internal and
external laryngoceles using an external approach. Tracheostomy is not required unless the
airway is entered. Laryngopyoceles require incision and drainage first. Endoscopy is
recommended, because a carcinoma may cause a laryngocele by creating a check valve in
the ventricle.

FIGURE 77.3. Computed tomography of an internal
laryngocele.



Pseudotumor of Infancy
Pseudotumor of infancy affects 0.4% of all newborns. Pseudotumor of infancy typically
presents as a firm rounded mass within the sternomastoid muscle 2 to 3 weeks after birth.
They usually present at the junction of the upper and middle third of the muscle and are
nontender. Differential diagnosis includes congenital lateral neck masses and neoplasia.
Diagnosis can be made by ultrasonography. Treatment is conservative, with between
80% and 100% complete resolution by the first birthday. Between zero and 20% progress
to congenital muscular torticollis (9).
MIDLINE NECK MASSES
Thyroglossal Duct Cysts
Thyroglossal duct cysts develop from remnants of the thyroid anlage that descends from
the foramen cecum on the base of the tongue, beginning at day 17 of gestation. The
thyroid primordium passes anterior, posterior, or through the hyoid bone in its descent in
the midline of the neck. Thyroid remnants may remain at any site along this route and
form cysts or fistulas (10).
Thyroglossal duct cysts present as cystic midline neck masses anywhere along the path of
the thyroid anlage's descent. They usually present in young children, although they may
be found in patients of any age. Thyroglossal duct cysts are usually 2 to 4 cm in diameter
and gradually increase in size. They may enlarge rapidly after an upper respiratory tract
infection. They elevate on protrusion of the tongue. Fistulae are the result of infection
drained surgically or spontaneously to the skin. Thyroglossal duct cysts should be treated
surgically, attempting to remove the cyst and the entire tract to the base of the tongue.
Attempts at local excision lead to a high recurrence rate. If the central portion of the
hyoid bone and a cuff of the tongue base are included in the specimen as described by
Sistrunk (11), the recurrence rate drops to 3% (5). Carcinomas have been reported to arise
from thyroglossal duct cysts. Adjunctive thyroidectomy in these cases remains
controversial.
Thymic Cysts
During the sixth week of fetal life, the third pharyngeal pouch gives rise to the paired
primordia of the thymus gland. By the ninth week, the thymus has descended below the
clavicles, and the superior end of the thymus has regressed. Thymic remnants may persist
as cords of cysts along the path of migration from the angle of the mandible to the
midline of the neck. Two thirds present to the left of midline (12).
Dermoid Cysts
Dermoid cysts are benign teratamatous lesions. They present as midline neck masses,
usually in the submental region (Fig. 77.4). Of head and neck dermoid cysts, 23% are
seen in the floor of mouth. They rarely present laterally. They contain varieties of tissues
of ectodermal and mesodermal origin. The main differential diagnosis is a thyroglossal
duct cyst. Dermoid cysts do not elevate with tongue protrusion as do thyroglossal duct
cysts. If they raise the floor of the mouth, a dermoid cyst may be mistaken for a ranula.
Treatment is by surgical excision.

FIGURE 77.4. Submental dermoid cyst.



Plunging Ranulas
Plunging ranulas are pseudocysts of the floor of the mouth, caused by mucous
extravasation from a blocked sublingual gland. Plunging ranulas may appear as isolated
submental masses or in association with a visible sublingual ranula (Fig. 77.5). They are
usually just off the midline. The main differentiation is from a dermoid. Treatment
includes excision in continuity with the sublingual gland of origin (13).

FIGURE 77.5. A: Plunging ranula. B: Intraoral view of
the same patient.



Teratomas of the Neck
Teratomas of the neck present in newborns, often with acute respiratory symptoms due to
tracheal compression. There may be associated esophageal compression. The lesions are
large, semicystic, and encapsulated. They frequently involve the thyroid gland and cause
symptoms because of their size. The masses are made of mature elements of ectoderm,
mesoderm, endoderm, and immature embryonal tissue. The main differential diagnosis is
lymphatic malformation. Lymphatic malformations are cystic and have ill-defined
borders. Ultrasound shows mixed echogenicity with teratomas rather than a multilocular
pattern seen with lymphatic malformations. Emergent surgical excision is required (14).
MASSES OF ENTIRE NECK
Lymphatic Malformations
Lymphatic malformations are benign, multiloculated, soft, painless, compressive masses
that usually present at or shortly after birth. The incidence has been reported to be 1.2 to
2.8 per thousand (15). Lymphatic malformations arise from the same primordia as do
normal lymph vessels. They are more common in the posterior triangle of the neck but
may extend across the midline.
Cervical lymphatic malformations rarely cause symptoms other than the cosmetic
deformity (Fig. 77.6). Large masses in the anterior neck may produce airway or
pharyngeal compression. This may be heightened by a sudden enlargement after an upper
respiratory tract infection or from hemorrhage into the mass. Mortality rates of 3% to 5%
have been reported. Differential diagnoses include branchial cysts, thyroglossal duct
cysts, and most other cysts and masses of the neck. Diagnosis is based on physical
examination and findings of thin-walled multiloculated cysts on ultrasound and computed
tomography or magnetic resonance imaging. Treatment is individualized and remains
primarily surgical excision, with care not to violate normal structures. Recurrence rates
vary between 20% and 50% (15). Because a lymphatic malformation usually does not
follow natural planes of cleavage, the dissection may be tedious, and recurrences are not
unusual. Sacrifice of normal neural and major vascular structures should be avoided.

FIGURE 77.6. Lymphatic malformation in an infant.



Hemangiomas
Hemangiomas are the most common head and neck neoplasms in children. They are
primarily cutaneous and mucosal but may be located in deep tissues.
Fewer than one third of hemangiomas are present at birth. They usually present in the
first few months of life and progressively enlarge over the next 12 months. In almost 90%
of cases, involution occurs, and therapy may not be necessary (16). Invasive
hemangiomas occur in deep subcutaneous tissues and deep fascial layers and muscles and
are unlikely to regress spontaneously. They most commonly present as a painful localized
rubbery swelling, with distinct margins and a smooth surface. The trapezius, scalene, and
sternomastoid muscles are most frequently involved. Coincident skin involvement is
uncommon (17).
Treatment must be individualized. Most congenital hemangiomas involute spontaneously
and may be treated conservatively and with support for the family. For deep-seated
hemangiomas of the head and neck, wide-field surgical excision remains the treatment of
choice. Care must be taken to avoid damage to vital structures. Steroids and laser may be
useful adjuncts to excision, but irradiation and sclerosing agents are no longer
recommended (16) (Table 77.3, Table 77.4, Table 77.5, Table 77.6 and Fig. 77.7).

TABLE 77.3. DIAGNOSIS CONGENITAL
NECK MASSES



TABLE 77.4. TREATMENT CONGENITAL
NECK MASSES



TABLE 77.5. COMPLICATIONS
CONGENITAL NECK MASSES



TABLE 77.6. EMERGENCIES CONGENITAL
NECK MASSES



FIGURE 77.7. Algorithm for management of congenital
neck masses.





HIGHLIGHTS
Congenital masses are the most common noninflammatory neck
masses in children. They usually present at birth but can appear
at any age.
Each mass has a typical presentation and location in the neck.
BA, laryngoceles, and pseudotumors of infancy present
laterally.
The presentation of BA can be predicted by a knowledge of the
embryology of the branchial apparatus. Second BA are the most
common and present anterior to the sternomastoid muscle in the
neck. External laryngoceles also may present anterior to the
sternomastoid muscle.
Pseudotumors of infancy present at 3 to 4 weeks of age as a
painless mass within the sternomastoid muscle. They can be
diagnosed on ultrasound.
Laryngoceles are air-filled herniations of the saccule of the
laryngeal ventricle.
Thyroglossal duct cysts present as midline neck masses that
move with swallowing. They are formed by a remnant of
thyroid anlage after its descent from the foramen cecum.
Excision requires removal of a core of the hyoid bone as
described by Sistrunk.
Thymic cysts, dermoid cysts, and plunging ranulas are seen in
the midline and present as mass lesions.
Teratomas also present in the midline, but they are usually seen
in newborns, cause acute respiratory symptoms due to tracheal
compression, and require urgent intervention.
Lymphatic malformations and hemangiomas present throughout
the neck and often cross the midline. Unlike cutaneous
hemangiomas, invasive hemangiomas do not regress
spontaneously.
For all nonresolving masses of the head and neck other than
pseudotumors, surgical excision without the sacrifice of normal
neural and vascular structures is the treatment of choice.
Pseudotumors are treated conservatively.
CHAPTER REFERENCES
1. Kenealy JF, Torsiglieri AJ, Tom LW. Branchial cleft anomolies: a five-year retrospective review.
Trans Penn Acad Ophthalmol Otolaryngol 1990;42:10221025.
2. Chandler JR, Mitchell B. Branchial cleft cysts, sinuses and fistulas. Otolaryngol Clin North Am
1981;13:175.
3. Sadler TW. Langman's medical embryology, 8th ed. Philadelphia: Lippincott Williams and
Wilkins, 2000.
4. Work WP. Cysts and congenital lesions of the parotid glands. Otolaryngol Clin North Am
1977;10:339.
5. Telander RL, Deane SA. Thyroglossal and branchial cleft cysts and sinuses. Surg Clin North Am
1977;57:779.
6. Sanborn WD. A branchial cleft of fourth pouch origin. J Pediatr Surg 1972;7:82.
7. Cote DN, Gianoli GJ. Fourth branchial cleft cysts. Otolaryngol Head Neck Surg 1996;114:95.
8. Rosenfeld RM, Biller HF. Fourth branchial pouch sinus: diagnosis and management. Otolaryngol
Head Neck Surg 1991;105:44.
9. Maddalozzo J, Goldenberg JD. Pseudotumor of infancy: the role of ultrasonography. Ear Nose
Throat J 1996;75:248254.
10. Allard RH. The thyroglossal duct cyst. Head Neck Surg 1982;5:134146.
11. Sistrunk WW. The surgical treatment of cysts of the thyroglossal tract. Ann Surg 1920;71:120.
12. Wagner CW, Vinocur CD, Weintraub WH, et al. Respiratory complications in cervical thymic
cysts. J Pediatr Surg 1989;23:657660.
13. Batsakis JG. Non-neoplastic disease of the salivary glands. In: Batsakis JG, ed. Tumors of the
head and neck: clinical and pathological consideration, 2nd ed. Baltimore: Williams & Wilkins,
1979:100120.
14. April MM, Ward RF, Garelick JM. Diagnosis, management, and follow-up of congenital head and
neck teratomas. Laryngoscope 1998;108:13981401.
15. Orvidas LJ, Kasperbauer JL. Pediatric lymphangiomas of the head and neck. Ann Otol Rhinol
Laryngol 2000;109:411421.
16. Stal S, Hamilton S, Spira M. Hemangiomas, lymphangiomas, and vascular malformations of the
head and neck. Otolaryngol Clin North Am 1986;19:769796.
17. Batsakis JG. Vasoformative tumors. In: Batsakis JG, ed. Tumors of the head and neck: clinical
and pathological consideration, 2nd ed. Baltimore: Williams & Wilkins, 1979:291312.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

78 CONGENITAL ANOMALIES OF THE NOSE
Head & Neck SurgeryOtolaryngology
78




CONGENITAL ANOMALIES OF THE NOSE
ROY B. SESSIONS
CATHERINE PICKEN

R.B. Sessions: Department of OtolaryngologyHead and Neck Surgery, Beth Israel Medical Center, New
York, New York.
C. Picken: Department of Otolaryngology, Georgetown University Medical Center, Washington, DC.


Embryology
Nasal Dermoids
Embryology
Clinical Presentation
Evaluation
Treatment
Gliomas and Encephaloceles
Embryology
Clinical Presentation
Evaluation
Treatment
Chapter References
Nasal dermoids, gliomas, and encephaloceles are congenital midline nasal lesions that are
believed to share a similar embryopathogenesis. To varying degrees, these defects are
part of a developmental complex that can involve cranial abnormalities. Although they
are uncommon, they are noteworthy because they present interesting clinical and
developmental problems. These anomalies are especially significant because of their
potential connection to the central nervous system (CNS).
All encephaloceles and many dermoids and gliomas communicate with the CNS.
Consequently, no congenital nasal mass or nasal polyp in a young child should be
manipulated in any way until intracranial communication is ruled out. Computed
tomography (CT) and magnetic resonance imaging (MRI) are the diagnostic studies of
choice, and neurosurgical consultation is considered in all cases. Treatment is surgical.
Adequate exposure and the cosmetic result are factors to consider in choosing the
approach, and microsurgical techniques may be helpful. Dermoids must be completely
excised to prevent recurrence. Table 78.1 summarizes the diagnosis, treatment, and
complications of congenital nasal anomalies.

TABLE 78.1. CONGENITAL ANOMALIES OF THE
NOSE



EMBRYOLOGY
It is impossible to explain clearly the nature, location, or potential complications
associated with these congenital abnormalities without reviewing the normal
development of the anterior cranial base. In this development there are two crucial
processes: the formation of the neural tube from ectoderm and the migration of neural
crest cells into mesenchyma to form the skull base and facial structures.
By the third week of gestation, a midline neural groove develops along the dorsal surface
of the embryo. This plate of ectoderm thickens, deepens, and finally forms a neural tube,
which fuses at the fourth week and goes on to form the nervous system. Neural tube
closure starts in the mid-portion of the embryo and progresses both anteriorly and
posteriorly, leaving neuropores at each end to close last. The anterior neuropore is
believed to be located at the site of the optic recess of the sphenoid; that area just
proximal to the neuropore forms the frontal, nasal, and ethmoidal structures.
Simultaneously, neural crest cells in the lateral portions of the neural tube begin
migrating between that tube and the surface ectoderm into the mesenchyma that is
destined to develop into bone and cartilage. The anterior neuropore area is devoid of
neural crest cells, which must reach this area by migrating from the neural tube more
posteriorly and laterally on the embryo. The anterior neuropore region therefore is
especially vulnerable to developmental errors; it represents the most distal end of the
closed neural tube and the most distal point of neural crest cell migration. The
mesenchyma destined to develop into the cranium and face is supplied by the neural crest
cells; however, the factors that modulate the crucial developmental process of migration
of these cells are poorly understood. Most of the pertinent research has been carried out
in avian or amphibian embryos, and very little is known about mammalian systems (1).
Although much more remains to be learned about the complex cellular and chemical
factors that controls embryonic development, it is clear that certain features of the
extracellular matrix and of the cells themselves play important roles. Work with chick
embryos has shown that changes in cell adhesion properties of neural crest cells alter
their migration and that proteins in the extracellular matrix probably serve a permissive
or inductive role in migration (1).
Whatever the process, once neural crest cells reach their destinations, the mesenchyma
begins organizing and condensing into mesodermal elements at various centers, which
later fuse with one another and ossify. Before closure, there are potential spaces between
forming bone and cartilage in well-recognized areas. The space between the frontal and
nasal bones is called the fonticulus nasofrontalis, and the space between the nasal bones
and nasal capsule (which will form the nasal cartilages and septum and which is
continuous with the ethmoidal labyrinth) is known as the prenasal space. The space
between the frontal and ethmoid bones is called the foramen cecum and is continuous
with the prenasal space (Fig. 78.1). All have been shown to contain firm fibrous tissue
(2). These spaces are normally obliterated during fetal development. It should be clear
that at early stages of development there is intimate contact between neuroectoderm and
surface ectoderm before the mesenchyma thickens and develops into the structures that
separate these layers. This is especially true at these gaps between forming bone.

FIGURE 78.1. A: Normal fetal anatomy. 1, Frontal
cartilage; 2, fonticulus nasofrontalis; 3, nasal bone; 4,
nasal cartilage; 5, prenasal space; 6, nasal capsule; 7,
dura. B: Normal closure of fonticulus, foramen cecum,
and prenasal space. C: Patent foramen cecum with fistula
to nasal dorsum through prenasal space. D: Patent
fonticulus and sinus tract to glabellar skin.



NASAL DERMOIDS
The term nasal dermoid is loosely used to describe a range of nasal anomalies varying
from a short epithelium-lined tract on the nasal dorsum to tracts extending from nasal
dorsal skin through the septum to the dura and, rarely, the cerebral ventricle. Dilations at
various points of the tract are called dermoid cysts; however, the basic pathology is the
skin-lined tract. These cysts histologically can contain epithelium and skin appendages
such as hair, hair follicles, and sweat and sebaceous glands. This diversity of contents is
what distinguishes dermoid cysts from simple epidermal inclusion cysts. Some dermoids
present as isolated masses in the nose, septum, or intracranial cavity without sinus tracts.
Embryology
It is widely agreed that dermoids are congenital abnormalities. Many theories have been
advanced to explain their occurrence and location. The simplest of these theories suggests
that dermoids represent clusters of epithelium that became trapped at the time of fusion of
ectodermal process (3). This would explain some of the simple dermoids that are not
associated with tracts. Another theory proposes that the middle layer of the fetal nasal
septum represents an extension of dura, a structure of ectodermal origin. Normally this
layer is obliterated as the septum fuses and ossifies. Failure to do so traps ectoderm in the
septum and results in a sinus tract or cyst that connects to the dura or the developing
cerebral ventricle (4).
The most widely accepted theory focuses on the prenasal space and fonticulus and on the
proximity of neuroectoderm to skin early in development (2,3,5). If skin maintains its
attachment to the fibrous tissues of the nasal capsule in the prenasal space or at the
fonticulus, epidermal elements can be drawn under the developing bones, forming a tract.
If attachments to dura exist in the same area, a tract could develop between nasal skin and
dura that passes through the prenasal space to the foramen cecum or through the
fonticulus. Bone could then condense around the tract (Fig. 78.2C and Fig. 78.2D). Cysts
may develop at any location along these tracts, including intracranially.

FIGURE 78.2. Pit on nasal dorsum. This child had a
history of recurrent drainage.



Probably no single theory explains all cases of dermoid. Rather, it is more likely that
certain aspects of these various theories apply to different dermal deformities.
Clinical Presentation
Dermoid sinuses and cysts generally occur in the nasal midline. They can present as a pit
(Fig. 78.2), a fistulous tract, or a mass anywhere from the nasal tip to the glabella.
Histologically, typical dermoids are also found in the nasomaxillary groove and nasal tip
but do not have sinus tracts and have different clinical significance. Dermoids are
uncommon, and there does not seem to be an increased incidence of associated congenital
abnormalities. Although there are sporadic reports of familial occurrence, dermoids are
not generally considered to be hereditary (6,7). Hair or sebaceous material may protrude
from the pit, and patients may present with recurrent drainage (Fig. 78.3), infections, and
possibly even meningitis. Dermoids located in the septum may present with swelling
internally in the septum or on the nasal septum.

FIGURE 78.3. Infected dermoid sinus cyst.



The location and appearance of these nasal lesions give no clue to the depth of
penetration of an associated sinus tract. Although dermoids most commonly terminate in
a single subcutaneous tract, these tracts may be multiple. Also, deeper involvement may
occur in up to 45% of patients, and extension intracranially has been noted in 25% to
30% of cases (2,8,9). If a deep tract does exist, it penetrates the nose at the junction area
between the nasal bones and the upper lateral cartilages. The tract is then encased in the
septum and can continue up to the cribriform plate to enter the skull base at the foramen
cecum just anterior to the crista galli. Such a tract may, of course, extend along only part
of this potential course. Some dermoids have a tract that penetrates the skull between the
frontal and nasal bones, and some combine both paths (2). It is believed that because
ectodermal elements accumulate, dermoid cysts expand with time.
When a nasal mass associated with a cutaneous fistula is observed, the diagnosis of
dermoid is obvious. However, the differential diagnoses in patients with only a nasal or
septal mass include hemangioma, epidermoid cyst, glioma, or encephalocele.
Evaluation
Radiologic studies are important in studying the extent of the lesion and most importantly
in judging the likelihood of intracranial involvement before any attempted treatment. CT
and MRI are the imaging studies of choice and yield different information. CT is used to
delineate the bony anatomy of the skull base. The findings on CT that suggest deep but
extracranial involvement by the dermoid include a fusiform swelling or bifidity of the
bony nasal septum, widening of the nasal vault, or glabellar erosion (2,10). A patent
foramen cecum and bifid crista galli suggest intracranial involvement; in such cases, an
anterior fossa mass may be present in the area immediately anterior to the crista galli.
These radiographic findings are not necessarily diagnostic, because deformities of the
crista galli and patency of the foramen cecum may be present without any intracranial
component of the dermoid. With such findings in the area of the crista galli, however,
there is a reasonable possibility of an associated intranial mass (2).
Interpreting radiographic findings in children is especially difficult because a thickened
nasal septum and broad nasal vault are normal. MRI is increasingly used for its superior
ability to image soft-tissue masses. In addition, it also visualizes the entire cyst and tract
in the direct sagittal plane (8,11). One or both of these imaging techniques are necessary
before treatment of a presumed dermoid is undertaken.
Treatment
Dermoids may be complicated by recurrent local infections or even meningitis. Also,
cosmetic deformity may be progressive as a cyst expands. Temporary relief can be
obtained with incision and drainage, but this should be discouraged. The entire tract
should be meticulously excised to prevent recurrence.
The surgeon must remember that nearly half of these lesions may penetrate deep to the
nasal bones and up to one third may connect to dura; the surgical approach should be
planned accordingly. Bartlett et al. (12) and Posnick et al. (13) observed that intracranial
involvement does not occur in masses that present above the nasofrontal suture. In
patients in whom a high suspicion of intracranial extension exists (i.e., suggestive
radiologic findings or a history of meningitis), a craniofacial approach should be planned.
Tracts that traverse the foramen cecum to enter intracranially go on into that potential
space between the two layers of the falx cerebri to lie in a gully just anterior to the crista
galli. If there is a mass in this area, most authors believe that craniotomy should be
performed first, followed by excision of the extracranial portion (2,9,14,15).
Most dermoids do not have an intracranial communication and can be safely approached
externally. We believe that the vertical midline incision on the nasal dorsum is the most
efficient approach to extracranial dermoids (2,16). Cosmetic results are good, and the
incision affords excellent exposure for removal of lesions that extend deep to the nasal
bones. Medial osteotomies and outfracturing of the nasal bones for exposure of these
deep tracts may be necessary and are easily performed and repaired through the vertical
incision. An external rhinoplasty approach, which can be extended with paraoral
incisions, has been offered as an alternative approach for selected dermoids; however, the
excellent cosmetic result must be weighed against the limited exposure this approach
offers (16). The bicoronal flap approach may also be useful for dermoids at the root of
the nose (17). In all cases, the nasal pit is excised with an ellipse of skin in continuity
with the sinus tract (16).
Microsurgical techniques, including the use of high-speed otologic drills, greatly aid the
accurate dissection of deep sinus tracts. Additionally, the magnified binocular
visualization possible with the operating microscope is extremely valuable in certain deep
dissections.
If a tract is found extending to the skull base, the surgeon must determine whether it is a
simple fibrous band that can be safely amputated without risk of recurrence or
cerebrospinal fluid (CSF) leak or whether it is an epithelium-lined stalk. This can be
accomplished with frozen sections of the stalk at the time of surgery. The presence of
epithelium in the stalk at the skull base warrants an intracranial approach to completely
and safely excise the entire tract.
Cosmetic defects caused either by the cyst itself or by its removal may be significant, and
every effort to accurately replace and realign the nasal bones is made. If secondary
reconstruction is required, it should be delayed until nasal growth is complete. The
patients and their parents should be counseled about scars, nasal deformity, and the
potential need for later reconstructive surgery.
The timing of surgery is not critical except in the rare cases complicated by meningitis.
Because cysts tend to expand with time and may cause progressive deformity, surgical
removal in the first 2 or 3 years of life is recommended (2). Dermoids associated with
intracranial masses are worrisome, and their removal is best accomplished early.
GLIOMAS AND ENCEPHALOCELES
Gliomas and encephaloceles are considered together because of their strikingly similar
clinical appearance, histology, and embryogenesis. Gliomas are unencapsulated
collections of glial cells in a connective tissue matrix that may retain attachments to the
dura. They are clearly congenital and are not neoplastic. Encephaloceles are herniations
of the meninges with or without brain tissue through the skull base and by definition
communicate with the CSF-containing subarachnoid space.
Embryology
Various theories have been suggested to explain gliomas (1). Some believe that they are
simply sequestered glial tissues of olfactory bulb origin that were amputated as the
cribriform plate fused and ossified. It has also been suggested that gliomas evolve from
misplaced but predestined cells that subsequently develop into nervous tissue at an
ectopic location (Fig. 78.4). Most probably, gliomas and encephaloceles are
developmentally related, with gliomas representing pinched-off encephaloceles (Fig.
78.4). This speculation is supported by the fact that some gliomas retain a fibrous
attachment to the CNS. They have also been reported in extranasal areas such as the
orbit, palate, and nasopharynx, all of which are well-known locations for encephaloceles.

FIGURE 78.4. A: Normal anatomy. 1, Frontal cartilage;
2, fonticulus nasofrontalis; 3, nasal bone; 4, nasal
cartilage; 5, prenasal space; 6, nasal capsule; 7, dura. B:
Herniation of dura and glial tissue (encephalocele)
through fonticulus. C: Closure of bones to form glioma.
D: Intranasal glioma with connection to the central
nervous system.



There are two principal theories of encephalocele formation (3). The first proposes
incomplete separation of the closed neural tube from surface ectoderm, resulting in a
mechanical barrier to neural crest cell migration and a resultant lack of bone formation in
that area. This does not occur at the neuropore only but anywhere along the line of
closure of the neural tube (i.e., the dorsal axis). The second theory places greater
emphasis on the failure of delay of migration of neural crest cells to their normal
destinations. As we have previously noted, neural crest cells must migrate into the
anterior cranial region, and the midline represents the farthest point of this migration.
Although the nature of the primary disturbance in migration is unknown, it is speculated
that failure of migration would result in an area of mesenchyma devoid of the neural crest
cells necessary for normal bony formation, leading to a defect in the cranium.
Theoretically, if migration were merely delayed, subsequent normal bony formation
could amputate neural tissue and form gliomas.
Clinical Presentation
Gliomas are rare congenital masses that usually present early in life but can on occasion
present in adulthood. They may manifest as an extranasal mass, an intranasal mass, or
both. Unlike dermoids, they do not routinely occur in the midline, nor do they connect to
a sinus tract to the skin. The skin overlying these masses may, however, be adherent to
the mass (18). They are firm noncompressible masses that do not expand with straining
or crying and do not transilluminate. External nasal gliomas are the most common (60%).
They are usually found at the glabella but may present as a lateral nasal mass. Thirty
percent of gliomas present as a unilateral intranasal mass that may prolapse from the
nares, and the remaining 10% combine both external and intranasal components.
Intranasal gliomas attach to the middle turbinate or higher in the lateral nose and can be
confused with polyps. The combined intranasal and extranasal lesions are dumbbell-
shaped, with a connecting band passing through the junction of the upper lateral cartilage
and nasal bone (3).
Overall, 15% of gliomas connect with the dura (15,19). Although this is rarely seen in
extranasal lesions, almost one third of those with an intranasal component does so. Some
of this latter group communicates with the CSF-containing subarachnoid space. There
have been reports of gliomas that secrete CSF without any apparent connection to the
CNS, but in such a circumstance we would question the diagnostic evaluation. When a
central connection exists, it occurs either through the foramen cecum or between the
frontal and nasal bones. Thus, gliomas can present with CSF rhinorrhea or meningitis.
Neither a familial incidence nor an association with other congenital abnormalities has
been demonstrated with nasal gliomas (3,19).
Gliomas must be differentiated from encephaloceles because the treatment and prognosis
are quite different. Encephaloceles are more serious abnormalities that consist of tissues
prolapsed through a defect in the cranium and are in continuity with the CNS. They may
be classified according to the contents of the herniated sac: Meningoceles contain
meninges, and encephaloceles contain meninges and glial tissue. By convention,
however, all are referred to as encephaloceles. They are also commonly classified by the
location of the defect in the skull base; thus, they are either occipital, sincipital, or basal
(20). The occipital variety occurs over the occiput and is beyond the scope of this
discussion. The sincipital or basal varieties occur in or near the nose.
Sincipital encephaloceles are also known as frontoethmoidal encephaloceles because the
skull base defect is always between the frontal and ethmoid bones at the foramen cecum,
which is located just anterior to the cribriform plate. Sincipital encephaloceles may be
further subdivided into the following (21,22):
1. Nasofrontal (Fig. 78.5B): The sac passes directly forward between the frontal and
nasal bones. The nasal bones are normal but displaced downward. The medial
orbital walls may be displaced laterally by mass effect. These lesions are located
at the glabella.
2. Nasoethmoidal (Fig. 78.5C): After leaving the cranium through the foramen
cecum, the sac passes downward below the nasal bones and above the upper
lateral cartilages to present as a mass on the lateral nose. The frontal and nasal
bones and the frontal process of the maxilla are normal and form the roof of the
defect. The floor of the defect is the upper nasal cartilage and the septum, which
are distorted by the mass.

3. FIGURE 78.5. A: Normal anatomy. B:
Nasofrontal encephalocele, with bony
defect above nasal bones. C:
Nasoethmoidal encephalocele, with bony
defect beneath nasal bones. E, ethmoid
bone; M, maxilla; N, nasal bones; NC,
nasal cartilage.
4.


5. Nasoorbital: Through the same skull base defect, the sac extends under the frontal
and nasal bones to protrude through a defect in the medial orbital wall.
There are four types of basal encephaloceles (22):
1. Transethmoidal: The sac herniates through a defect in the cribriform plate into the
superior meatus and extends medial to the middle turbinate.
2. Sphenoethmoidal: The sac extends through a cranial defect between the posterior
ethmoidal cells and sphenoid to present in the nasopharynx.
3. Transsphenoidal: The sac protrudes through a patent craniopharyngeal canal to
present in the nasopharynx.
4. Sphenomaxillary: The encephalocele herniates through the superior orbital fissure
and then through the inferior orbital fissure to present in the sphenomaxillary
fossa.
Occipital encephaloceles are by far the most common (75%), followed by the sincipital
group (15%), of which the nasofrontal variant is the most common (21). Basal types are
rare, with the transethmoidal type being the most common of this group (20).
Most sincipital encephaloceles present as a soft compressible mass over the glabella.
Typically, they are described as pulsatile, and they expand with crying or straining or
with compression of the jugular veins (Furstenberg test). None of these features may be
present, however, and they may appear only as firm masses. There are reports of
congenital scars overlying these masses (21). The basal types usually show little external
evidence of their presence, except perhaps widening of the root of the nose and
hypertelorism. These patients usually present with symptoms related to nasal obstruction
(3). Intranasal encephaloceles may resemble polyps but, unlike polyps, are located medial
to the middle turbinate and are intimately related to the nasal septum rather than to the
lateral nose. This is in contrast to gliomas, which are attached laterally. These features,
plus the fact that polyps are very rare in children, should help prevent confusion.
Intranasal encephaloceles may or may not be compressible. They can also present as a
nasopharyngeal mass and have been mistaken for adenoid tissue.
Although there does not appear to be a familial incidence for encephaloceles, they are
associated with significant congenital abnormalities in 30% to 40% of cases. It has been
observed that encephaloceles that are transmitted through the sphenoid bone have the
highest incidence of serious coexisting anomalies (23). These anomalies include varying
degrees of hydrocephalus, cerebral malformations, optic abnormalities, and median cleft
face features. Depending on the amount and location of herniated brain tissue and also on
associated abnormalities, the prognosis can range from excellent to grave.
Evaluation
Any child presenting with an external or internal nasal mass requires careful radiologic
evaluation. No nasal mass should be dismissed as a simple polyp. Because of the risk of
causing meningitis, aspiration or biopsy of these masses is contraindicated.
CT and MRI are the studies of choice. Patients with gliomas typically have no evidence
of bony dehiscence of the cranium. A mass with such a dehiscence is considered an
encephalocele. Another finding associated with some encephaloceles is the low position
of the roof of the ethmoid relative to the orbit. CT is best for detecting bony
abnormalities, but MRI is superior for accurately showing the interface of the soft-tissue
mass to the CNS.
Treatment
Lesions with any potential for connection with the brain should be managed jointly by the
otolaryngologist and the neurosurgeon. Gliomas should be completely excised whenever
possible to minimize cosmetic deformity and the risk of meningitis. Encephaloceles
expand with time, and this has been shown to cause increasing hydrocephalus and
increasing herniation of brain tissue into the sac and progressive cosmetic deformity. In
addition, a persistent risk of meningitis exists. All these factors dictate an expeditious
assault on the problem.
Extranasal gliomas can be approached through standard external incisions, depending on
the location of the mass. Combined lesions or intranasal masses can be approached
through a lateral rhinotomy. Microsurgical techniques may be useful. Recurrences of
gliomas in the overlying skin have been reported, and it has been suggested that adherent
overlying skin should be excised in continuity with the glioma (18). If a stalk extends to
the skull base, the surgeon must determine if it is merely a fibrous band or if it contains
nervous tissue. If glial tissue is identified in a stalk at the skull base, the mass should be
handled like an encephalocele, as described below.
The management of encephaloceles and those gliomas suspected to have intracranial
communications is primarily neurosurgical, with excision of the extracranial components
performed secondarily. Gliomas not suspected of cranial connections can be approached
externally as the primary procedure, although it is wise to have neurosurgical assistance
available if it becomes necessary.

HIGHLIGHTS
Nasal dermoids, gliomas, and encephaloceles have shared
embryopathogenesis and pose similar management problems
because of communication with the CNS.
Nasal dermoids range from a short epithelium-lined tract on the
nasal dorsum to tracts from the nasal skin through the dura.
Hair or sebaceous material may protrude from the nasal skin
pit.
Radiographic studies are essential to determine the degree of
intracranial extension of a nasal dermoid and the surgical
procedure appropriate for management.
Nasal gliomas are unencapsulated collections of glial cells in a
connective tissue matrix that may retain a dural attachment.
Encephaloceles are herniations of the meninges through the
skull base and may or may not contain brain tissue. They
communicate with the CSF-containing subarachnoid space.
Gliomas usually present early in life and may manifest as
intranasal or extranasal masses. External (usually glabellar)
gliomas are more common (60%); only 15% of the gliomas
connect with the dura.
Sincipital (frontoethmoidal) encephaloceles may present in
three patterns: nasofrontal (glabellar), nasoethmoidal (lateral
nose), or nasoorbital (into orbit).
Encephaloceles are usually soft compressible masses that are
pulsatile or expand with crying or straining. Intranasal
encephaloceles resemble nasal polyps.
CT and MRI are the studies of choice for gliomas and
encephaloceles. Bony dehiscence indicates an encephalocele
rather than a glioma.
Surgical excision is the preferred treatment for dermoids,
gliomas, and encephaloceles.
CHAPTER REFERENCES
1. Bronner-Fraser M. Adhesive interactions in neural crest morphogenesis. In: Maderson P, ed.
Developmental and evolutionary aspects of the neural crest. New York: John Wiley and Sons,
1987:21.
2. Sessions R. Nasal dermoid sinuses: new concepts and explanations. Laryngoscope 1982;[Suppl
92]:29.
3. Hengerer A. Congenital anomalies of the nose: their embryology, diagnosis, and management.
Monograph. Philadelphia: American Academy of Otolaryngology Head and Neck Surgery, 1987.
4. Littlewood A. Congenital nasal dermoid cysts and sinuses. Br J Plast Surg 1961;16:169.
5. Pratt L. Midline cysts of the nasal dorsum: embryologic origin and treatment. Laryngoscope
1965;75:968.
6. Kahn M, Gibb A. Medical dermoid cyst of the nose: familial occurrence. J Laryngol Otol
1970;84:709.
7. Plewes J, Jacobson I. Familial frontonasal dermoid cysts. J Neurosurg 1971;34:683.
8. Fornadley J, Tami T. The use of magnetic resonance imaging in the diagnosis of nasal dermoid
sinus-cyst. Otolaryngol Head Neck Surg 1989;101:397.
9. McQuown S, Smith J, Gallo A. Intracranial extension of nasal dermoids. Neurosurgery
1983;12:531.
10. Johnson G, Weisman P. Radiologic features of dermoid cysts of the nose. Radiology 1983;82:16.
11. Lusk R, Lee P. Magnetic resonance imaging of congenital midline nasal masses. Otolaryngol
Head Neck Surg 1986;95:303.
12. Bartlett SP, Lin KY, Grossman R, et al. The surgical management of orbitofacial dermoids in the
pediatric patient. Plast Reconstr Surg 1993;9:1208.
13. Posnick JC, Bortoluzzi P, Armstrong DC, et al. Intracranial nasal dermoid sinus cysts: computed
tomographic scan findings and surgical results. Plast Reconstr Surg 1994;93:745.
14. Clark W, Bailey R, Stiernberg C. Nasal dermoid with intracranial involvement. Otolaryngol Head
Neck Surg 1985;92:102.
15. Frodel J, Larrabee W, Raisis J. The nasal dermoid. Otolaryngol Head Neck Surg 1989;101:392.
16. Pollock R. Surgical approaches to the nasal dermoid cyst. Ann Plast Surg 1983;10:498.
17. Cauchus R, Laccourreye O, Bremond D, et al. Nasal dermoid cyst. Ann Otol Rhinol Laryngol
1994;103:615.
18. Thompson HG, Al-Qattan MM, Becker LE. Nasal glioma: is dermis involvement significant? Ann
Plast Surg 1995;34:168.
19. Gorenstein A, Kern E, Facer GW, et al. Nasal gliomas. Arch Otolaryngol 1980;106:536.
20. Blumenfeld R, Skolnick E. Intranasal encephaloceles. Arch Otolaryngol 1965;82:527.
21. Charonsmith T, Suwanhela C. Frontoethmoidal encephalomeningocele with special reference to
plastic reconstruction. Clin Plast Surg 1974;1:27.
22. Suwanhela C, Suwenhela N. A morphological classification of sincipital encephaloceles. J
Neurosurg 1972;36:201.
23. Moore MH, Lodge ML, David DJ. Basal encephalocele: imaging and exposing the hernia. Br J
Plast Surg 1993;46:497.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

79 PEDIATRIC RHINOSINUSITIS
Head & Neck SurgeryOtolaryngology
79




PEDIATRIC RHINOSINUSITIS
RODNEY P. LUSK

R.P. Lusk: Department of Pediatric Otolaryngology, St. Louis Children's Hospital, St. Louis, Missouri.


Signs and Symptoms
Physical Examination
Diagnostic Aids
Etiology
Bacteriology
Medical Management
Surgical Management
Adenoidectomy
Antral Lavage
Inferior Meatal Antrostomy or Nasal Antral Windows
Middle Meatal Antrostomy
Ethmoidectomy
Endoscopic Sinus Surgery
Complications and Emergencies
Orbital Complications
Intracranial Complications
Chapter References
The goal of this chapter is to review the diagnosis, etiology, medical and surgical
management of pediatric rhinosinusitis (RS). The diseases compatible with RS are
extensive and difficult to differentiate (Table 79.1). Family practitioners, pediatricians,
and otolaryngologists are increasingly aware of sinus disease in children. Purulent
rhinorrhea is not the norm, and society as a whole appears to be less tolerant of it. The
day-care setting magnifies the problem of purulent rhinorrhea, especially if the parents
are forced to find alternative care when the child is ill. Day-care children have a greater
exposure to upper respiratory tract infections, which may progress to RS. Because young
children experience six to eight upper respiratory infections a year, the persistent nasal
symptoms may not be RS but rather those of another cold (1). The difficulty in
distinguishing the two conditions may result in the unnecessary use of antibiotics,
possibly potentiating the emergence of resistant organisms.

TABLE 79.1. DIAGNOSIS DIFFERENTIAL
DIAGNOSIS OF DISEASES COMPATIBLE WITH
PEDIATRIC CHRONIC SINUSITIS



SIGNS AND SYMPTOMS
The low specificity for RS signs and symptoms makes diagnosis difficult. Acute upper
respiratory tract infections are frequently mistaken for RS. The primary delineation
between the two is the chronicity of the infection. Wald et al. (1) noted that symptoms of
the common cold subside in 5 to 7 days, and if longer than 10 days, are likely to reflect
an acute RS or persistent symptoms of chronic RS. The issue becomes even more
confused when practitioners prescribe antibiotics for all upper respiratory tract infections.
A consensus panel on the management of pediatric RS established the following criteria
to distinguish the different forms of RS. Acute RS is defined as an infection with
complete resolution of clinical symptoms by 12 weeks with no intervening upper
respiratory tract infections. Recurrent acute RS occurs when the signs and symptoms of
an acute infection resolve completely between episodes. Chronic RS occurs when the
patient has symptoms or signs that persist for longer than 12 weeks (2). The panel also
divided the signs and symptoms of acute RS into severe and nonsevere (Table 79.2).

TABLE 79.2. SYMPTOMS AND SIGNS OF
PEDIATRIC RHINOSINUSITIS



The history and physical findings for acute RS vary with the patient's age. Young patients
often have nasal congestion and purulent anterior rhinorrhea. Older patients may not be
as symptomatic but often complain of nasal congestion, postnasal drip, or sore throat due
to the chronic drainage. Cough, a frequent complaint, is more frequent at night. The
presence of daytime cough, however, is more specific for acute or chronic RS. An
isolated nighttime cough is usually a residual symptom from the recent upper respiratory
infection or nocturnal asthma.
The pain of acute RS may manifest in a variety of ways. Younger children can be
irritable and exhibit head banging. The older patient complains of headaches and is able
to localize the pain. For chronic infections, facial pain is infrequent. In the older child,
chronic RS complaints include nasal obstruction, decreased sense of smell, and a metallic
taste.
Nasal examination of RS patients may reveal congestion, discharge, or absence of
airflow. The color of the nasal discharge varies among clear, yellowish, and greenish.
Clear drainage is frequently associated with allergies, whereas yellow or greenish
rhinorrhea is frequently but not always indicative of a bacterial infection. Another clue
that allergies may be contributing to the problem is the presence of allergic shiners, the
dark lower eyelids with puffiness over the maxilla.
In contrast to bacterial RS, an uncomplicated viral infection is of short duration. Fever
when present appears only at the onset of nasal symptoms. The nasal discharge of a viral
infection is initially clear, but becomes thicker and opaque after a few days. By the end of
a week, the child is feeling better rather than worse (1).
Physical Examination
A child's lack of cooperation may make the physical examination difficult (Table 79.3).
The approach to the child must be slow and nonthreatening. If the child's confidence
cannot be gained, examination of the nose will be impossible. Once the child starts
crying, tears will interfere with the examination. Head movements from side to side and
the narrowing of the nasal vestibule brought on by crying make the examination virtually
impossible.

TABLE 79.3. PHYSICAL EXAMINATION IN
CHRONIC SINUSITIS



The tools used to examine the nasal vault include a nasal speculum and head mirror,
microscope and nasal speculum, otoscope, flexible nasal pharyngoscope, or rigid
telescope. The Viroscope (Welch Allen) offers a unique method of performing anterior
nasal examinations. The headlight is quite bright, and the anterior nasal airway can be
viewed through lenses that reduce parallax and allow good binocular vision of the
anterior nasal airway.
Regardless of the method used, anterior rhinoscopy is all that can be accomplished unless
one uses a flexible scope. The otoscope is a good all-round instrument to evaluate a
child's nose. It is best first to examine the ears. If the child tolerates this and the physician
has gained the child's confidence, the nose is examined with the otoscope. If all goes
well, one may vasoconstrict nasal mucosa with 0.05% oxymetazoline. After several
minutes, the nose is reexamined to evaluate for pus that has emerged from the sinuses
into the anterior nasal vault. Polyps are unusual except in children with cystic fibrosis or
allergic fungal sinusitis. Only large polyps are visible on anterior rhinoscopy. By
examining the middle meatus, one can note stasis of secretions in this area. RS is less
likely if this area is clear and free of edema (Fig. 79.1; see also Color Plate 24 following
p. 370). Examination with a rigid telescope is possible in the unusually cooperative child,
using local anesthesia. Rolling a 2.7-mm telescope into the middle meatusfrequently
done in adultsis virtually impossible in children. The physical examination alone may
suggest the presence of RS but is not conclusive.

FIGURE 79.1. Normal left middle meatus (see also
Color Plate 24 following p. 370).



Diagnostic Aids
Table 79.4 lists diagnostic modalities that are potentially useful in the evaluation of
chronic RS. Some physicians perform transillumination in adults, but the sinuses in
children are small, and transillumination offers no diagnostic advantages.
Ultrasonographic imaging has been found to be inconsistent with plain radiography. Plain
films are also suspected of being inaccurate (3). A major criticism of these diagnostic
aids is that they focus attention primarily on the maxillary sinus.

TABLE 79.4. OTHER DIAGNOSTIC AIDS FOR
PEDIATRIC CHRONIC SINUSITIS



Computed tomography (CT) scanning rather than plain films is a more accurate method
to document RS. McAlister and associates at St. Louis Children's Hospital prospectively
studied 70 children who had symptoms of chronic RS and compared the plain films with
the coronal CT scans. The two studies were obtained within a few hours of each other,
and vasoconstrictive agents were not applied. The plain radiographs and CT scans were
interpreted independently by pediatric radiologists and neuroradiologists. Forty-five
percent of the children with normal plain radiographs showed abnormalities on CT scan,
and 34% of the children with abnormal plain radiographs had normal CT scans. These
results suggest that plain films are unreliable as a screening tool. The plain films both
over- and underestimate the amount of sinus disease noted on CT scans (3). This finding
does not negate the use of plain films in acute disease where air-fluid levels may be
found, but it does demonstrate the limitations of plain films. The CT scan has become the
gold standard for the evaluation of chronic RS in children, and radiation from the CT
scan is equivalent to that of sinus films. Figure 79.2A is the plain film on a postoperative
patient, and Figure 79.2B is the coronal CT scan performed on the same day. Notice that
the mucosal thickening noted in the maxillary sinus on the CT scan results in almost
complete opacification on the plain film.

FIGURE 79.2. A: Plain radiograph of a child who has
had endoscopic sinus surgery. Notice the opacification of
the right maxillary sinus and significant mucous
membrane thickening of the left maxillary sinus. The
ethmoid sinuses are difficult to assess on this film. B:
Computed tomography scan of the same patient, taken
about 20 minutes later. There is no disease in the ethmoid
cells, and true mucous membrane thickening of the right
maxillary sinus was represented as opacification on the plain films. The right maxillary
sinus is clear except for thickening along the roof of the sinus. Note that the maxillary
antrostomies are widely patent.



The consensus panel states that imaging is not necessary to confirm the diagnosis of RS
in children. The indications for sinus CT include (a) severe illness or toxic condition in a
child, (b) acute RS that does not improve with medical therapy in 48 to 72 hours, (c)
immunocompromised host, and (d) presence of a suppurative complication other than
orbital cellulitis. These indications are identical to the panel's recommendations for
performing a sinus puncture and collecting a culture (2). A sinus CT scan is required for
any patient that is to have sinus surgery.
ETIOLOGY
Clinicians now recognize that infections of the nasal mucosa and sinuses are a continuum
of disease. Rhinitis or sinusitis rarely occurs in isolation. Most pediatric sinus infections
begin as viral upper respiratory infections and progress to bacterial RS (4). The viruses
most frequently encountered in acute RS are rhinovirus, parainfluenza, influenza, and
adenovirus (1). An area particularly prone to obstruction is the ostiomeatal complex. The
frontal, anterior ethmoid, and maxillary sinuses drain into this area. Ostiomeatal complex
obstruction can cause an infection of these sinus cavities. Either anatomic abnormalities
or mucosal inflammation can be responsible for the ostial obstruction. Upper respiratory
tract infections, allergies, reflux, or barotrauma can all produce inflammation. Our
understanding is that persistent inflammatory obstruction of the natural sinus ostium
results in chronic RS.
For many years, physicians believed that anatomic variations adjacent to the ostiomeatal
complex were associated with a higher incidence of chronic RS. In our experience, this
has not been the case. Children with septal deviations, paradoxical turbinates, and
infraorbital cells do not have a higher incidence of chronic RS. Patients with concha
bullosa actually had a lower incidence of RS by CT evaluation. The reason for this
finding is unclear. Of note, the CT scans in this study were obtained in children on 4
weeks of broad-spectrum antibiotics and topical nasal steroid sprays.
Ciliary function plays an important role in the health of the paranasal sinuses. Chronic RS
is associated with cilia that beat slower and less efficiently. When two ciliated surfaces
touch, ciliary clearance is disrupted and pooling of secretions may occur. In the area of
the ostium, these secretions may become secondarily infected and produce a chronic RS.
Ciliary function is important because sinus ostia are small and may be located in
positions that are not conducive to gravitational drainage. Kartagener syndrome is an
example of ciliary dysfunction, and virtually all these patients have chronic RS. Some
investigators believe that gastroesophageal reflux disease plays a major role in the
etiology of chronic RS. They note that the parallel existence of upper airway
inflammation, intractable RS, and gastroesophageal reflux suggests a causal relationship
(5). Definitive studies that prove the association between reflux and sinusitis have not
been performed. Allergy is a risk factor for chronic RS. The etiology for this association
is probably ostial obstruction. The frequency of sinus infections, however, does not
correlate with the times of the year when allergies are most prevalent. Most episodes of
RS occur during the winter, when viral upper respiratory tract infections are at their
greatest. This lack of correlation calls into question the role of allergies in RS; however,
environmental and food allergies may play a significant role for nonseasonal RS. A
variety of immune deficiencies also have been associated with chronic RS. The
consensus panel recommendation regarding the etiology of RS is that in the presence of
recalcitrant RS, underlying conditions such as allergy, immunodeficiency, cystic fibrosis,
ciliary immotility disorders, and gastroesophageal reflux have to be considered (2).
BACTERIOLOGY
Most RS microbiology studies have focused on acute RS. Wald and colleagues found that
Streptococcus pneumoniae was the most common organism (30%), followed closely by
Moraxella catarrhalis and Haemophilus influenzae (20%). H. influenzae is usually
nontypable. Both M. catarrhalis and H. influenzae have a high incidence of -lactamase
producing enzymes and therefore are resistant to many antibiotics. Anaerobes and
staphylococci are rarely found in acute sinusitis. One fourth of patients with bilateral
maxillary RS had discordant bacterial cultures. The failure to detect viral organisms may
result from cultures being collected 10 days after the onset of symptoms. The bacteria
involved with subacute infections (i.e., infections of 10 to 21 days) are similar to those of
acute RS, with M. catarrhalis and H. influenzae the most common (Table 79.5).

TABLE 79.5. MOST COMMON BACTERIA OF
CHRONIC PEDIATRIC SINUSITIS



Despite the importance of chronic RS, few studies have investigated its microbiology. A
possible explanation is the paranasal sinus inaccessibility. In younger patients, a
maxillary sinus puncture will require a general anesthetic. Brook and colleagues found a
high incidence (approximately 50%) of anaerobic bacteria in maxillary sinus contents (6).
Most of the anaerobes were anaerobic cocci and Bacteroides. The anatomy of the
maxillary sinus may favor a more anaerobic environment. Muntz and Lusk (7) evaluated
the microbiology of the ethmoid bulla in 105 children who had failed aggressive medical
management. Patients with immunodeficiency and cystic fibrosis were excluded from
this study. The principal organisms isolated were -hemolytic Streptococcus,
Staphylococcus aureus, M. catarrhalis, S. pneumoniae, and H. influenzae nontype B.
Only 12 anaerobic organisms and four fungi were isolated. Forty of the ethmoidal bullae
did not yield organisms at the time of culture. These data continue to hold in more than
600 cultures. The authors concluded that antibiotic therapy for chronic RS should cover
-hemolytic Streptococcus and S. aureus as well as the other bacteria noted in acute and
recurrent RS.
Recently, an alarming increase in the incidence of resistant bacteria of the upper
respiratory tract has occurred. Resistance of S. pneumoniae to penicillin and other
antimicrobial agents is increasing throughout the world. Epidemiologic studies have
shown that frequent use of antibiotics and the use of prophylactic antibiotics to prevent
otitis media are risk factors for the spread of resistant strains. Particularly troublesome are
institutional environments, such as day-care centers and hospitals. The incidence of
resistant bacteria is therefore higher in children and in more affluent families because of
their greater use of antibiotics (8). The changing resistance patterns will lead to changes
in the types of antibiotics used and may well change the indications for surgical
intervention.
MEDICAL MANAGEMENT
Mechanical cleaning of the nasal airway with saline irrigation is increasingly recognized
as valuable in the treatment of chronic RS. Parsons (9) provides an excellent recipe for
buffered hypertonic saline for nasal irrigation as well as suggestions for its use. Prior to
surgical intervention, treatment for other causes of RS, including allergy and
immunodeficiency, should be instituted.
Antibiotic therapy continues to be the cornerstone of medical management. The treatment
of acute and recurrent RS should cover S. pneumoniae, M. catarrhalis, and H. influenzae.
These three bacteria account for 70% of the bacteria causing RS. Seventy-five percent of
the M. catarrhalis and 30% of the H. influenzae bacteria are -lactamase producers. In
1986, Wald and associates found that 40% of the episodes of acute RS undergo
spontaneous cure. If this is the case, the role of -lactamase producers is reduced to about
10%. For acute RS, amoxicillin alone remains a reasonable choice if the infection is
uncomplicated. The appropriate duration of antibiotic therapy has not been systematically
studied in children. Empirically, acute RS is usually treated for 10 to 14 days, with
improvement in symptoms at 48 to 72 hours. If significant improvement has not
occurred, an alternative antibiotic should be considered. If the patient is still symptomatic
at the end of the first course of treatment, the antibiotic should be continued for 7 to 10
additional days. Some areas of the country have a high incidence of bacterial resistance,
and alternative primary antibiotics may be required. For a complicated or protracted RS
infection, an antibiotic that covers -lactamaseproducing organisms is the most
appropriate (Table 79.6).

TABLE 79.6. RECOMMENDED ANTIMICROBIAL
MANAGEMENT



To assist selection of appropriate antibiotics, a treatment guideline has been published.
Antibiotic selection depends on the severity of symptoms, the date of the last course of
antibiotics, and the local microbial resistance pattern. Antibiotic recommendations for
patients with mild RS who have not received antibiotics in the previous 4 to 6 weeks
include amoxicillin (45 to 90 mg/kg/day), cefpodoxime proxetil, or cefuroxime axetil.
Prior to prescribing antibiotics for mild RS, one must realize that the predicted
spontaneous resolution rate of children with acute bacterial RS is 49.6%. If a child has
either mild RS but has received a recent course of antibiotics or moderate RS, the
following antibiotics are suggested: amoxicillin/clavulanate, amoxicillin (80 to 90
mg/kg/day), cefpodoxime proxetil, or cefuroxime axetil. The rationale for still
recommending cefpodoxime proxetil or cefuroxime axetil is that these drugs are still
active against microorganisms that are mildly resistant to penicillin. If a patient has
moderate RS as well as a recent course of antibiotics, the following medication options
are available: amoxicillin/clavulanate alone or combination therapy with an antibiotic that
has good gram-positive coverage (amoxicillin or clindamycin) and another with gram-
negative coverage (cefpodoxime proxetil or cefixime). The guideline's authors provided a
ranked order of antibiotics by predicted efficacy: >90%, amoxicillin/clavulanate; 80% to
90%, amoxicillin (80 to 90 mg/kg/day), cefpodoxime proxetil, cefuroxime axetil,
cefixime (based on H. influenzae and M. catarrhalis coverage only), clindamycin (based
on gram-positive coverage only), and the macrolide antibiotics; 70% to 80%, cefprozil
(10).
Studies to evaluate the efficacy of prophylactic antibiotics in the treatment of recurrent or
chronic RS have not been performed. One is tempted to use prophylactic antibiotics
because there has been considerable success with this treatment for otitis media with
effusion. This practice, however, has come under increasing scrutiny with the emergence
of resistant bacteria.
One should consider the role of anaerobes in patients with chronic RS. Gram-positive
anaerobic streptococci and staphylococci are generally penicillin susceptible and
therefore present no medical therapeutic problems. Gram-negative Bacteroides species
producing -lactamase respond well to amoxicillin/potassium clavulanate.
Adjunctive medical modalities, such as antihistamines, topical or oral decongestants,
topical or oral steroids, and antiinflammatory agents, have not been studied in children or
adults. We currently use topical nasal steroid sprays in all our patients, but this is an
empiric method of treatment and cannot be supported by prospective data.
SURGICAL MANAGEMENT
Table 79.7 summarizes the surgical treatment of pediatric RS.

TABLE 79.7. SURGICAL MANAGEMENT OF
PEDIATRIC CHRONIC SINUSITIS



Adenoidectomy
Previous investigations have shown an association between children with adenotonsillar
disease and RS. St. Clair and Negus (11) found that rhinorrhea was treated effectively
with antibiotics alone in 11 of 50 patients, whereas the cure rate with tonsillectomy and
adenoidectomy was only 18 of 50 patients. A relationship may exist between the size of
the adenoid and the frequency of RS. Few people advocate a tonsillectomy as part of the
surgical management plan. The St. Louis Children's Hospital experience is that the
majority of true chronic RS in young patients is not effectively treated with
adenoidectomy alone. Because a large adenoid pad may mimic all the symptoms of
sinusitis, and stasis of secretions may result in recurrent RS, an adenoidectomy for an
enlarged pad is reasonable. Rosenfeld (12) has proposed a stepped treatment approach to
treating refractory RS. He believes adenoidectomy to be appropriate as first-line
treatment.
Antral Lavage
Antral lavage has been described as a method both to detect and to treat recurrent
sinusitis. One of its obvious deficiencies is that it addresses only the maxillary sinus, and
we now understand that the ethmoid sinuses are involved with equal frequency. The
lavage can be performed through the natural ostium, the inferior meatus, or the canine
fossa (Fig. 79.3). The role of antral lavage in the treatment of chronic RS is unclear. One
author (11) recommended that the lavage takes place as early as possible and argued that
it should be used as a primary mode of therapy. Rarely is lavage successful with only one
intervention. Multiple lavages and anesthetics before proceeding to other surgical
modalities are no longer a practical option.

FIGURE 79.3. The three possible routes for maxillary
sinus irrigation. (1) Through the natural ostium of the
maxillary sinus: a curved suctionirrigator must be placed
behind the uncinate process and engage the natural
ostium. (2) Through the inferior meatus: this is limited by
how well the floor of the maxillary sinus is developed. (3)
Through the anterior wall of the maxillary sinus: this is
done by going under the lip and through the gingival
sulcus and is limited by the permanent teeth.



Inferior Meatal Antrostomy or Nasal Antral Windows
Although the inferior meatal antrostomy has been frequently used to treat chronic
sinusitis, many clinicians question its effectiveness (13). The rationale for the inferior
meatal antrostomy is to provide aeration and dependent drainage. Little scientific
evidence exists for its efficacy. A critical question regarding this treatment is antrostomy
patency over time. Lund (13) determined that the antrostomy had to be larger than 1 cm
to remain patent, which presents a significant limitation in children. Another study, in 39
children who were treated with bilateral inferior meatal antrostomies for chronic sinusitis,
found that symptoms were not controlled in 60% of patients at 1 month and 73% at 6
months (14). These results are not surprising. Cilia will continue to beat toward the
obstructed natural ostium even if a patent opening exists elsewhere. Except in children
with ciliary dyskinesia, dependent drainage does not occur. Due to the poor long-term
patency and low likelihood of controlling sinus symptoms, inferior meatal antrostomy is
nonbeneficial as a primary mode of therapy (14).
Middle Meatal Antrostomy
In a series of animal experiments from the 1940s, the authors concluded that opening of
the natural ostium would increase the incidence of maxillary sinus infections. Only
recently have studies refuted these findings (15). Many surgeons are advocating a limited
rather than a wide antrostomy (16). Today, opening the natural maxillary sinus ostium is
considered the most physiologic method to ventilate the maxillary sinus (17). Creating an
accessory ostium will not drain the sinus because the cilia will continue to beat toward
the obstructed natural ostium. This problem is termed the missed ostium sequence (18).
If the natural ostium later becomes patent, a recirculation phenomenon can occur where
secretions leave the natural ostium and reenter the sinuses through the accessory ostium.
Ethmoidectomy
Ethmoidectomy has been used as a method of treating complicated chronic sinus disease
in adults and children. It can be performed through the external, intranasal, or transantral
approaches. The transantral approach has not gained widespread acceptance in children
because of the small maxillary sinus size and the risk of traumatizing the tooth buds. The
unaided intranasal approach has not been used because of the smaller ethmoid cavity size
and increased risk of complications in children.
Endoscopic Sinus Surgery
With the advent of the Hopkins rod-lens system and appropriate pediatric endoscopic
instruments, ethmoidectomy and maxillary antroscopy can now be safely performed in
children whose parents feel 80% are normal after endoscopic sinus surgery and 11%
revision rate. Terris and Davidson (19) reviewed the adult and pediatric literature for
endoscopic sinus surgery and found 1,713 patients who had undergone surgery; 91%
were improved. Subjectively, 63% reported very good, 28% good, and 9% unsatisfactory
results. The revision rates were around 12%. These findings are consistent with our own
findings in children.
The absolute and relative indications for endoscopic sinus surgery are found in Table
79.8. Prior to surgical intervention, a coronal CT scan confirms the presence of chronic
RS and detects any anatomic lesions that could increase the risk of an operative
complication.

TABLE 79.8. INDICATIONS FOR ENDOSCOPIC
SINUS SURGERY



The goal of endoscopic ethmoidectomy is to eradicate the disease while being as
conservative as possible. An anterior ethmoidectomy and limited maxillary antrostomy
will usually address most of the pathology seen in pediatric RS (5) (Fig. 79.4 and Fig.
79.5; see also Color Plate 25 following p. 370). Extensive sphenoethmoidectomy is not
justified in children unless they have symptomatic polyps from cystic fibrosis or allergic
fungal sinusitis. There has been concern about interrupting facial growth in young
children. This fear is based on animal studies that show asymmetry of the snout after
surgery. We have evidence, in unpublished work, that facial growth in children is not
altered with endoscopic sinus surgery at 10 years out (20).

FIGURE 79.4. A and B: Coronal and sagittal
reconstruction of a patient with symptoms and ethmoid
disease significant enough to warrant endoscopic
ethmoidectomy. C and D: Postoperative computed
tomography scans show good resolution of disease.



FIGURE 79.5. Postoperative view of cavity after an
anterior ethmoidectomy (see also Color Plate 25
following p.370).



COMPLICATIONS AND EMERGENCIES
Table 79.9 summarizes complications of RS.

TABLE 79.9. COMPLICATIONS PERSISTENT
SINUS DISEASE



Orbital Complications
Complications of acute and chronic RS are best recognized and treated early. Most arise
from extension of acute infections into the orbit and cranial cavity. The most common
complications of RS involve the orbit. Orbital complications in young children frequently
respond to medical treatment. Older children are more likely to require surgical
intervention (21). Infections from the sinuses can spread to the orbit through the arteries,
veins, or rarely lymphatics but most often by direct extension through a dehiscence in the
lamina papyracea (Fig. 79.6).

FIGURE 79.6. Potential routes for expansion of infection
from the ethmoid to the orbit.



The signs and symptoms of orbital complications can be used to stage the disease and
guide management. The classification proposed by Chandler and colleagues (22) has
gained the widest acceptance (Fig. 79.7):

FIGURE 79.7. Progressive stages of inflammation of the
orbit.



Group 1: Inflammatory (preseptal) edema of eyelids without tenderness, obstruction of
venous drainage, no associated visual loss or limitation of ocular movements.
Group 2: Orbital cellulitis with diffuse edema of the adipose tissue in the orbital contents
secondary to inflammation and bacterial infection, no abscess formation.
Group 3: Subperiosteal abscess: abscess formation between the orbital periosteum and
the bony orbital wall. The mass displaces the globe in the opposite direction (usually
down and lateral), and the proptosis may be severe with decreased ocular mobility and
visual acuity. The abscess may rupture into the orbit through the orbital septum.
Group 4: Orbital abscess: a discrete abscess within the orbit. Proptosis is usually severe
but is symmetric and not displaced as in the subperiosteal abscess. Complete
ophthalmoplegia results, and visual loss occurs in 13%.
Group 5: Cavernous sinus thrombosis: progression of the phlebitis into the cavernous
sinus and to the opposite side, resulting in bilateral symptoms.
These stages are important because they help specify the treatment and define the
prognosis.
The physical examination is important. Proptosis can occur with any inflammatory
reaction within the orbit. If the proptosis is symmetric, the entire orbit is likely to be
involved; if it is asymmetric, there is likely to be a mass in the opposite quadrant that is
causing the proptosis (Fig. 79.8). In general, the greater the proptosis, the greater the
pressure and the more severe the infection. An axial CT scan is the best method to
diagnose subperiosteal and orbital abscesses. The most likely pathologic organisms are
identical to those that produce acute RS: S. pneumoniae, H. influenzae, M. catarrhalis,
and Streptococcus pyogenes. S. aureus is more frequent with chronic infections and in the
older child. Complications are almost always associated with acute RS.

FIGURE 79.8. A: Patient with asymmetric proptosis
secondary to a subperiosteal abscess. B: Axial computed
tomography scan of same patient.



Orbital cellulitis and abscesses are potentially life-threatening infections. Managing these
complications requires the expertise of many specialists. Medical management starts with
aggressive intravenous antibiotics that cross the bloodbrain barrier to prevent
intracranial infections. The indications for surgical intervention vary. Careful monitoring
of the vital signs, ocular motility, and visual acuity is necessary. If no improvement is
seen after 24 hours of intravenous antibiotics or if the patient's clinical status worsens, an
axial CT scan is performed to identify a possible abscess. If one is found, the abscess is
surgically drained. If there is a decrease in visual acuity, immediate evaluation and
surgical intervention are indicated. The visual loss can be caused by direct pressure on
the optic nerve or can be secondary to neuritis. Regardless of the cause, when the abscess
is drained, the visual loss usually reverses rapidly.
Subperiosteal abscess can be safely drained endoscopically. Children recover quicker
following endoscopic drainage, and the hospital stay is approximately half that for an
external approach. The endoscopic approach in an acutely infected sinus is technically
more difficult but associated with a lower incidence of complications than the external
approach in competent hands. Each surgeon must decide which procedure is the most
efficacious and safest in their hands.
An orbital infection that extends posteriorly into the cavernous sinus is life threatening
and has significant sequelae. Most patients who develop this complication from RS have
involvement of the sphenoid sinus. If cavernous sinus thrombosis or intracranial
complications are suspected, an emergent axial CT scan with contrast is indicated. In
cavernous sinus thrombosis, the CT scan will show a lack of contrast enhancement in one
or both cavernous sinuses. Aggressive intravenous antibiotic therapy should be directed
against gram-positive cocci (S. aureus) and gram-negative bacilli (23). If the sphenoid
sinus is involved, it should be drained through the ethmoid sinus.
Intracranial Complications
Intracranial complications include meningitis and epidural, subdural, and acute or chronic
brain abscess (Fig. 79.9). Brain abscesses are the most common intracranial
complications with RS and are exceeded in overall frequency only by orbital
complications. Common symptoms of intracranial abscess include fever, headache,
behavioral changes, seizures, nuchal rigidity, focal neurologic signs, and occasionally
photophobia. The most common abscess is the subdural, followed closely by the frontal
lobe abscess or a combination of the two (24). Intracranial sequelae are most likely to
occur in older children or adults because their paranasal sinuses are more developed.
Frontal lobe abscesses are often silent and difficult to diagnose on clinical grounds (24).
Many patients have none of the signs of increased intracranial pressure: bradycardia,
papilledema, stiff neck, hypertension, nausea, vomiting, and decreased consciousness
(24). A dilated pupil is an ominous sign and suggests transtentorial herniation. Patients
with epidural abscess generally present with a continuous dull headache and sudden
elevation of temperature (Fig. 79.10 and Fig. 79.11; see also Color Plate 26 following p.
370). Patients with subdural abscesses are toxic, with changes in mental status, severe
headaches, nuchal rigidity, focal neurologic changes, papilledema, and cloudy
cerebrospinal fluid with leukocytes but no bacteria or positive cultures. These abscesses
are thought to be the most dangerous intracranial complications and require emergent
surgery (25).

FIGURE 79.9. Subdural, epidural, and intercerebral
brain abscess.



FIGURE 79.10. Computed scan of patient with epidural
abscess secondary to a frontal sinus infection.
Craniotomy of same patient.



FIGURE 79.11. Craniotomy of patient with epidural
abscess secondary to a frontal sinus infection (see also
Color Plate 26 following p. 370).



Intracranial abscesses involve the same pathogens as ear infections and acute RS (S.
pneumoniae, H. influenzae, and M. catarrhalis). Chronic RS is associated with a much
higher incidence of S. aureus and -hemolytic streptococci. Medical therapy includes
antibiotics that pass through the bloodbrain barrier and cover the most frequently
cultured bacteria. Until a specific organism is identified, the 1998 Pocket Book of
Pediatric Antimicrobial Therapy recommends nafcillin or vancomycin and cefotaxime
and metronidazole. The duration of therapy is individualized. Exclusive medical
management appears to be most appropriate in patients in the cellulitis stage of abscess
formation. Surgical management is based on the extent and location of the disease. The
intracranial approach is dictated by the location of the lesion.

HIGHLIGHTS
The signs and symptoms of RS vary with the child's age and are
not diagnostic of sinusitis. Purulent nasal discharge, cough,
nasal obstruction, and irritability are the most common
symptoms.
The physical examination is limited to anterior rhinoscopy
because of the limited cooperation of the child and because of
the narrow pediatric nose.
Coronal CT scans are required to define the anatomy and the
extent of the disease.
The bacteria most often associated with pediatric RS are -
hemolytic Streptococcus, S. aureus, S. pneumoniae, M.
catarrhalis, and H. influenzae. The incidence of resistant strains
of bacteria is increasing.
Antibiotic selection for acute bacterial RS depends on the
severity of symptoms, the date of the last course of antibiotics,
and the local microbial resistance pattern.
Surgical modalities of questionable value are tonsillectomy,
antral lavage, and inferior antral windows. Adenoidectomy is
thought to improve symptoms in children with adenoid
hypertrophy, but it is unclear how much effect it has on
children with small adenoid pads.
Complications of RS usually are associated with acute
infections and result in extension into the orbital and
intracranial cavities. These infections are potentially life
threatening and have a high incidence of morbidity.
The etiology of chronic RS is multifactorial, and underlying
conditions such as allergy, immunodeficiency, cystic fibrosis,
ciliary immotility disorders, and gastroesophageal reflux should
be considered.
CHAPTER REFERENCES
1. Wald ER, Guerra N, Byers C. Upper respiratory tract infections in young children: duration of and
frequency of complications. Pediatrics 1991;87:129133.
2. Clement PAR, Bluestone CD, Gordts F, et al. Management of rhinosinusitis in children. Arch
Otolaryngol Head Neck Surg 1998;124:3134.
3. McAlister WH, Lusk RP, Muntz HR. Comparison of plain radiographs and coronal CT scans in
infants and children with recurrent sinusitis [Comments]. AJR Am J Roentgenol 1989;153:1259
1264.
4. Lusk RP, Stankiewicz JA. Pediatric rhinosinusitis. Otolaryngol Head Neck Surg
1997;117(suppl):5357.
5. Barbero GJ. Gastroesophageal reflux and upper airway disease: a commentary. Otolaryngol Clin
North Am 1996;29:2738.
6. Brook I, Thompson DH, Frazier EH. Microbiology and management of chronic maxillary
sinusitis. Otolaryngol Head Neck Surg 1994;120:13171320.
7. Muntz HR, Lusk RP. Bacteriology of the ethmoid bullae in children with chronic sinusitis.
Otolaryngol Head Neck Surg 1991;117:179181.
8. Hofmann JN, Cetron MS, Farley MM, et al. The prevalence of drug-resistant Streptococcus
pneumoniae in Atlanta. N Engl J Med 1995;333:481486.
9. Parsons DS. Chronic sinusitis: a medical or surgical disease? Otolaryngol Clin North Am
1996;29:19.
10. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg
2000;122(part 2):128.
11. St. Clair T, Negus VE. Diseases of the nose and throat. London: 1937:232.
12. Rosenfeld RM. Pilot study of outcomes in pediatric rhinosinusitis. Arch Otolaryngol Head Neck
Surg 1995;121:729736.
13. Lund VJ. Inferior meatal antrostomy: fundamental considerations of design and function.
Laryngol Otol Suppl 1988;15:118.
14. Muntz HR, Lusk RP. Nasal antral windows in children: a retrospective study. Laryngoscope
1990;100:643646.
15. Salam MA, Cable HR. Middle meatal antrostomy: long-term patency and results in chronic
maxillary sinusitis: a prospective study. Clin Otolaryngol 1993;18:135138.
16. Setliff RC III. Minimally invasive sinus surgery: the rationale and the technique. Otolaryngol Clin
North Am 1996;29:115124.
17. Kennedy DW, Zinreich SJ, Shaalan H, et al. Endoscopic middle meatal antrostomy: theory,
technique, and patency. Laryngoscope 1987;97:19.
18. Parsons DS, Stivers FE, Talbot AR. The missed ostium sequence and the surgical approach to
revision functional endoscopic sinus surgery. Otolaryngol Clin North Am 1996;29:169183.
19. Terris MH, Davidson TM. Review of published results for endoscopic sinus surgery. Ear Nose
Throat J 1994;73:574580.
20. Wiatrak BJ, Willging P, Myer CM III, et al. Functional endoscopic sinus surgery in the
immunocompromised child. Otolaryngol Head Neck Surg 1991;105:818825.
21. Hawkins DB, Clark RW. Orbital involvement in acute sinusitis: lessons from 24 childhood
patients. Pediatrics 1977;16:464471.
22. Chandler JR, Langenbrunner DJ, Stevens ER. The pathogenesis of orbital complications in acute
sinusitis. Laryngoscope 1970;80:14141429.
23. Macdonald RL, Findlay JM, Tator CH. Sphenoethmoidal sinusitis complicated by cavernous sinus
thrombosis and pontocerebellar infarction. Can J Neurol Sci 1988;15:310313.
24. Bradley PJ, Manning KP, Shaw MD. Brain abscess secondary to paranasal sinusitis. Laryngol
Otol 1984;98:719725.
25. Parker GS, Tami TA, Wilson JF, et al. Intracranial complications of sinusitis. South Med J
1989;82:563569.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

80 CLEFT LIP AND PALATE: EVALUATION AND TREATMENT OF THE PRIMARY DEFORMITY
Head & Neck SurgeryOtolaryngology
80




CLEFT LIP AND PALATE: EVALUATION AND
TREATMENT OF THE PRIMARY DEFORMITY
ROBIN A. DYLESKI
DENNIS M. CROCKETT
ROBERT W. SEIBERT

R.A. Dyleski and R.W. Seibert: Department of Pediatric Otolaryngology, Arkansas Children's Hospital,
Little Rock, Arkansas.
D.M. Crockett: Department of OtolaryngologyHead and Neck Surgery, University of Southern
California School of Medicine, Los Angeles, California.


Incidence and Genetics
Embryologic Considerations and Classification
General Team Management Approach
Initial Care and Psychosocial Issues
Nursing Care and Feeding Issues
Anatomic Deformity and Facial Growth
Unilateral Cleft Lip
Bilateral Cleft Lip
Cleft Palate
Facial Growth
Surgical Management of the Primary Deformity
Sequencing and Timing of Surgery
Surgical Technique: Lip Adhesion
Surgical Technique: Cleft Lip Repair
Surgical Technique: Cleft Palate Repair
Conclusion
Chapter References
Cleft lip with or without cleft palate [CL(P)] is the most common congenital
malformation of the head and neck. Evaluation and management requires a long-term
comprehensive and multidisciplinary program in terms of medical, surgical, dental, and
psychological intervention, usually in conjunction with a cleft palate team approach.
The purpose of this chapter is to present an overview of the initial and primary care
required for the child born with a cleft lip and/or palate: it is not intended to replace or
compete with more comprehensive texts on this subject. First, we discuss the incidence,
genetics, embryology, and classification of cleft lip and cleft palate, along with general
management of the infant. The second section discusses unilateral and bilateral cleft lip
repair, including timing of the operation, with goals and techniques of the procedure.
Third, the methods and timing of cleft palate repair are presented.
INCIDENCE AND GENETICS
Cleft lip and cleft palate are common congenital malformations (1), second only to
clubfoot (talipes equinovarus) in frequency of occurrence. Cleft lip with or without cleft
palate appears to be genetically distinct from isolated cleft palate without cleft lip (CP).
The former occurs in about 1 in 1,000 newborns in the United States (considering all
racial groups), the latter in about 1 in 2,000. The incidence of CL(P) varies by ethnic
group, with the highest frequency occurring in native Americans, about 3.6 in 1,000
births (1), followed by Asians with 2.1 in 1,000 births, whites with 1 in 1,000, and blacks
with 0.41 in 1,000 births (2). Conversely, the incidence of CP is constant among ethnic
groups (0.5 in 1,000) (2). Sex differentiation (male:female ratio) is about 2:1 for CL(P)
and 1:2 for CP. Overall, the prevalence of cleft types in the United States population is as
follows: complete clefts of the lip, alveolus, and palate, about 45%; cleft lip and/or
alveolus only, about 25%; and CP, about 30%.
Both CL(P) and CP can be further subcategorized as syndromic or nonsyndromic.
Syndromic refers to those clefts that are part of, or associated with, a recognized pattern
of human malformation or syndrome. The etiology of syndromic clefts may be single
gene transmission (mendelian inheritance: autosomal dominant, autosomal recessive, or
x-linked), chromosomal aberrations (trisomy, deletion, addition, or translocation),
teratogenic effects (ethanol, thalidomide, phenytoin), or environmental (amniotic band
syndrome, maternal diabetes mellitus, folate deficiency, tobacco smoke exposure).
Estimates of the percentage of syndromic etiologies in the cleft population have ranged
from as high as 60% to as low as 15%. More than 200 recognized syndromes are known
to include a facial cleft as a manifestation (Table 80.1). A thorough head and neck
examination and search for any other structural anomalies must occur to identify the
presence of a syndrome, such as synostosis, telecanthus, maxillary/malar hypoplasia,
abnormal pinnae or atresia, facial nerve paresis or paralysis, abnormal mandibular shape,
and excursion or malocclusion (1). Identification of a syndrome has important prognostic
implications and is important to the family in terms of genetic counseling.

TABLE 80.1. COMMON SYNDROMES WITH
FACIAL CLEFTS



Patients with a cleft are recognized as nonsyndromic when they have no other associated
head and neck anomalies, no organ system malformations, no known teratogenic or
environmental exposure history that predisposes to clefting, and normal cognitive
function and physical growth. Segregation analysis of clefting in populations suggests
that multifactorial inheritance is the etiology of nonsyndromic facial clefts, as evidenced
by the frequent occurrence of clefts in families across several generations without a
demonstrated mendelian pattern of inheritance. Because of this, calculated recurrence risk
rates based on studies of clefting in populations are necessary to provide genetic
counseling for families with children with nonsyndromic clefts (Table 80.2).

TABLE 80.2. RECURRENT RISK RATES FOR
CLEFT LIP, WITH OR WITHOUT CLEFT
PALATE, AND ISOLATED CLEFT PALATE



EMBRYOLOGIC CONSIDERATIONS AND CLASSIFICATION
Normal embryologic development of the lip and palate can be considered to occur in two
related phases: the first phase (beginning at 45 weeks' gestation), involving the
development of the upper lip, nose, and primary palate or premaxilla (the portion of the
palate anterior to the incisive foramen containing the four central and lateral incisors),
and the second phase (beginning at 8 to 9 weeks' gestation), involving the development of
the secondary palate (the hard and soft palate posterior to the incisive foramen).
Malformations in either phase resulting in a cleft may occur either separately, resulting in
a cleft anterior (cleft lip and alveolus) or posterior of the incisive foramen (cleft of the
secondary palate), or together, resulting in a complete cleft of the lip, alveolus, and
palate. Additionally, a cleft involving only the lip may occur as an isolated entity, but a
cleft of the alveolus is always associated with a cleft of the lip. The classic submucous
cleft palate (bifid uvula, midline diastasis of the levator muscles, and posterior hard
palate notching due to loss of the posterior nasal spine) is really a microform expression
of a cleft of the secondary palate.
The first phase involves proliferation of the mesoderm and ectoderm in the frontonasal
process. The frontonasal process has three components: (a) an anterior labial component,
which forms the philtrum; (b) an anterior palatal component forming the alveolar part of
the premaxilla (with the central and lateral upper incisors), and (c) a posterior palatal
component forming the portion of the hard palate anterior to the incisive foramen.
Laterally, proliferation of mesoderm with overlying ectoderm occurs in the maxillary
processes that eventually form the lateral lip segments and nasal alae.
Embryonic formation of the frontonasal process begins with differentiation of the
olfactory placode epithelium (3). Morphogenetic movement of the placode and
differential growth forms the characteristic curl of the placode into the nasal alae. The
most recent mechanism of palatal formation involves contact, with subsequent resorption
of the contacting surface epithelial cells and adhesion of the contacting prominence. It is
believed that this occurs in both primary and secondary palate formation, that is, contact,
loss of surface epithelial cells, and mesodermal contact, with fusion and penetration
across the junction. Differences in the gestational time of development and fusion of the
primary palate (about 30 days) and secondary palate (about 50 days) are reflected in the
separate genetic inheritance patterns.
The second phase, or development of the secondary palate, involves medial growth of the
palatal shelves (mesoderm) originating from the lateral maxillae. Initially, the shelves are
canted superiorly due to the tongue primordia, but they eventually shift inferiorly and
fuse at the midline. Fusion occurs first at the incisive foramen and progresses posteriorly
toward the uvula.
Understanding cleft embryogenesis allows an understanding of cleft classification.
Although no universally accepted system of terminology and classification of clefts
exists, a useful classification scheme (4) is that used by the Department of
OtolaryngologyHead and Neck Surgery at the University of Iowa (Fig. 80.1). Clefts of
the lip are either unilateral right or left, or bilateral (group I). They may be complete
(with extension into the nasal floor) or incomplete (extending from a slight muscle
diastasis at the vermilion to a small bridge of tissue at the nasal sill). Group III includes
children with a cleft lip and palate. Clefts of the palate can be divided into primary
(involvement anterior to the incisive foramen, group IV) or secondary (involvement
posterior to the incisive foramen, group II). Palatal clefts also may be unilateral (the
palatal process of one side is fused with the septum, resulting in communication of the
oral and nasal cavities on one side only) or bilateral (no connection between either palatal
process and the septum). A complete cleft palate refers to a cleft of both the primary and
secondary palates and is nearly always associated with a cleft lip. The term incomplete
cleft palate is synonymous with a cleft of the secondary palate or may be used to describe
a palatal cleft with an area of intact mucosa associated with a cleft lip.

FIGURE 80.1. Cleft classification scheme used by the
University of Iowa.



GENERAL TEAM MANAGEMENT APPROACH
Because the problems that confront affected children and their parents are complex,
variable, and long-term, the facial reconstructive surgeon should be allied with a cleft
palate or craniofacial team that meets regularly. This allows valuable consultation with
colleagues in pediatrics, plastic surgery, dentistry, orthodontics, speech pathology, and
audiology on a regular basis. Other experts may be consulted as needed, such as
neurosurgery, ophthalmology, and prosthodontics clinicians, as well as oral surgeons,
geneticists, nurses, and social workers. The team approach functions best as an
interdisciplinary manner for optimal functional and aesthetic results.
Initial Care and Psychosocial Issues
Following the birth of a child with a facial cleft, the parents often react with
disappointment and anger, followed by depression, then guilt. Initial counseling is
important and should be scheduled as soon as possible with a health care professional
skilled in counseling parents of children with craniofacial anomalies. This counseling
intervention should allow the parents to verbalize their feelings, and they should be
reassured that they are not responsible for the deformity. Care and feeding in the first
months of life should be explained, and a general outline for the child's long-term care
should be offered.
Nursing Care and Feeding Issues
The first medical priority is to establish adequate feeding and nutrition. Infants with a
cleft lip and/or alveolus often feed nearly normally by bottle or breast. Infants with
complete cleft lip and palate or CP often have significant feeding problems at first. In
general, in wider and more extensive clefts, more difficulty with feeding is seen from the
infant's inability to generate a sufficient seal around the nipple. This causes the infant to
tire easily, swallow a great deal of air, and require frequent burping. With education and
coaching, it is usually possible for the infant to feed with a preemie nipple (they are softer
and more easily conform to the cleft), or other specialty nipple, such as a Mead-Johnson
cross-cut nipple with squeeze bottle nurser (thus allowing improved flow of formula). An
upright position with chin support helps to minimize nasal regurgitation. Those babies
with a wide cleft and continued feeding problems will sometimes benefit from a palatal
prosthesis. The child may be discharged from the hospital when the parents are
comfortable with the chosen feeding technique and the child is adequately nourished and
hydrated. Frequent follow-up is necessary to ensure that the infant is gaining weight and
thriving.
ANATOMIC DEFORMITY AND FACIAL GROWTH
The anatomic deformity associated with CL(P) involves the soft tissues of the lip and
nose, the cartilaginous and bony supporting structures of the nose and palate, and the
underlying bony maxilla.
Unilateral Cleft Lip
Although the degree of deformity depends on the severity of the cleft, the orbicularis oris
muscle, blood supply, and innervation generally follows the external form or silhouette of
the cleft lip (5). For the incomplete cleft lip, the muscle fibers of the orbicularis oris are
intact but hypoplastic across the width of the cleft. In the complete cleft lip, the muscle
fibers are directed superiorly following the cleft margins and terminate at the columella
base medially and beneath the nasal ala laterally. There is often increased muscle bulk in
the lateral segment, whereas there is a deficiency of muscle in the medial segment. The
vermilion tends to be thinner on the medial side, which is an important fact to note during
the definitive lip repair.
The nasal deformity associated with the unilateral cleft lip involves the nasal ala, alar
base, columella, medial and lateral crura of the lower lateral cartilage, dome, and septum,
as well as the underlying maxilla. Because the lateral maxillary segment is often
displaced inferiorly, the alar base and lateral crus are displaced laterally and inferiorly.
As a result, the dome is flattened and rotated downward on the cleft side. The columella
is short, and the nostril is horizontally positioned on the cleft side.
Bilateral Cleft Lip
In the bilateral complete cleft lip and palate, the anatomy of the lateral lip segments is
similar to the unilateral cleft lip (6); however, orbicularis oris muscle fibers are absent in
the prolabium (the medial segment). The nasal deformity in the bilateral cleft lip often
involves a very short columella length, as well as widely flared alae with rotated and
displaced lower lateral cartilages. The premaxilla is often protruded with respect to the
lateral maxillary segments, which are often hypoplastic and displaced posteriorly. The
orbicularis oris muscle fibers rarely are found in the prolabium (medial lip segment) and
insert into the lateral cleft margins at the nasal base and alae region.
Cleft Palate
There are variable deficiencies associated with cleft palate depending on the location of
the defect. In the normal palate, the tensor veli palatini and levator palatini muscles
within the soft palate insert into an aponeurosis at the midline raphe. In the cleft palate,
the muscle fibers follow the medial margin of the cleft and insert into the medial cleft
edges and the posterior edge of the lateral bony hard palate. Clefts involving the alveolus
may disrupt normal dental eruption and tooth retention.
Facial Growth
The subject of normal human facial growth is extremely complex and incompletely
understood; superimposing a cleft defect complicates an already complex process. Many
children with clefts will develop collapse of the alveolar arches, mid-face retrusion, and
resultant malocclusion as they approach their teenage years. The underlying cleft
deformity itself, as well as the surgical procedures performed to correct the defect, have
been implicated as possible contributing etiologies. At present there is controversy
regarding the relationship between surgical procedures and maxillary growth in terms of
the sequencing of surgical procedures, the timing of the cleft repair, whether or not the
cleft lip repair itself has an effect on maxillofacial growth, and the various surgical
techniques of lip and palate repair.
SURGICAL MANAGEMENT OF THE PRIMARY DEFORMITY
Sequencing and Timing of Surgery
Lip Adhesion
The goal of a lip adhesion is to convert a complete cleft lip into an incomplete cleft lip,
allowing the definitive lip repair to be performed with less tension (7). The lip adhesion
acts as an orthopedic device and improves the alignment of the underlying maxillary
segments prior to the definitive lip repair. Lip adhesion, if indicated, is the initial
procedure and is performed at 2 to 4 weeks of age. Definitive lip repair follows the
adhesion at 4 to 6 months of age: this allows the scar to mature. The following criteria are
used to determine if lip adhesion is needed:
1. Wide unilateral complete cleft lip and palate where closure with conventional lip
repair might produce excessive tension on the incision
2. Symmetric wide bilateral complete cleft lip with a very protruding premaxilla
3. Introduction of symmetry to an asymmetric bilateral cleft lip
A disadvantage of lip adhesion is the introduction of scar tissue, which may occasionally
interfere with the definitive lip repair; although not usually a major concern, this has
prompted some surgeons to limit its use.
Cleft Lip Repair
If there are no medical contraindications, and a lip adhesion has not been performed
previously, definitive lip repair is accomplished at 10 to 12 weeks of age. In the United
States, most surgeons follow the rule of tens: lip repair is performed when the infant is
at least 10 weeks old, weighs 10 pounds, and has a hemoglobin of 10 g.
Cleft Palate Repair
Historically, the exact timing of surgical closure of the cleft palate has been controversial.
The desire to facilitate velopharyngeal competence for adequate speech favors relatively
early closure of the palate, whereas the possible negative influence on maxillofacial
growth and occlusion favors relatively late closure.
Anatomic factors to consider when evaluating the individual cleft palate include the
extent of the cleft; width (between both the alveolar ridge and palatal shelves); position of
the maxillary segments; and, in the bilateral cleft, the size, position, and degree of
protrusion of the premaxilla and prolabium. For the unilateral cleft, collapse of the lateral
maxillary segment may occur following the lip repair, or preoperative orthopedics may
be used to realign the maxillary segments in a more normal contour before the palate
repair. Sometimes a bilateral cleft palate with an extremely protruding premaxilla may
necessitate presurgical orthopedics to move the premaxilla posteriorly and expand the
lateral maxillary segments, allowing the surgical closure. After examining the patient,
and considering the factors noted above, it would be reasonable to consider closure of the
complete or incomplete cleft palate at 9 to 12 months of age.
Surgical Technique: Lip Adhesion
Unilateral Lip Adhesion
Before performing lip adhesion, the landmarks are marked as for a definitive Millard
rotationadvancement procedure (Fig. 80.2). This allows (5,8) for creation of small
rectangular mucosal vermilion flaps to be made superior to the landmarks, so as not to
interfere with the skin, muscle, and mucosa used in the definitive lip repair. The lateral
segment incision may be extended into the intercartilaginous junction of the upper and
lower lateral nasal cartilages for improved advancement and release of tension at the
attachment near the piriform aperture.

FIGURE 80.2. AD: Unilateral lip adhesion.



Suturing begins with placement of interrupted absorbable sutures in the inner lip mucosa,
which are temporarily left untied. A single nonabsorbable suture (3.0 clear nylon) is
placed in a stab incision on the cartilaginous septum on the noncleft side and passed
through the orbicularis oris muscle of the lateral lip element and then back through the
septum (this is also left untied temporarily). Finally, two to four absorbable sutures are
placed to approximate the medial and lateral lip muscles. The clear nylon suture is then
tied, the inner mucosal sutures are tied, and the exterior mucosa is closed with interrupted
absorbable sutures.
Bilateral Lip Adhesion
Bilateral lip adhesion is performed in a similar manner to unilateral lip adhesion (Fig.
80.3) (7). Lip landmarks are marked out as though the intention is to complete a
definitive bilateral lip repair. Lateral and medial mucosal flaps are created on both left
and right sides and sutured in a similar manner as for the unilateral lip adhesion. The
major difference between bilateral and unilateral adhesion is the placement of the
nonabsorbable retention suture. This is in general a horizontal mattress suture, placed
such that it incorporates the orbicularis oris muscles on the lateral lip element, and then
passed at the prolabiumpremaxilla junction submucosally. It, too, is tied just prior to
closure of the external mucosal incision.

FIGURE 80.3. AD: Bilateral lip adhesion.



Surgical Technique: Cleft Lip Repair
Several methods of definitive lip repair have been described (5,6,8,9 and 10). For
unilateral lip repair, the rotation advancement method (as described by Millard) is
probably the most commonly used technique in the United States and abroad. This
technique (5) matches a downward rotation flap on the medial lip with an advancement
flap on the lateral lip. A distinct advantage of this technique is that the scar of the suture
line recreates the natural philtral column. The second most commonly used method of lip
repair uses the interdigitation of triangular flaps (Tennison and Randall).
Repair of the bilateral cleft lip is more difficult, because no normal side exists to use as a
model during repair. For this reason, more techniques of bilateral lip repair and
modifications of these techniques have been described as compared with unilateral lip
repair.
Unilateral Cleft Lip Repair
The rotationadvancement method may be used for the entire spectrum of unilateral cleft
lips (5,8) (Fig. 80.4 and Fig. 80.5). The technique is described for a complete cleft lip and
palate. Although the basic design is unchanged, minor modifications in marking the lip
landmarks and flap design are necessary, depending on the individual anatomy (i.e., cleft
width, extent of lip tissue deficiency, extent of nasal deformity, and position of the
maxillary segments). The following section is a summary of the principal steps of the
technique.

FIGURE 80.4. Unilateral cleft lip repair.



FIGURE 80.5. A: Preoperative view of unilateral cleft
lip. B: Markings prior to repair. C: Final closure. D:
Postoperative appearance (age 12 months).



The landmarks of the lip are marked with a vital dye as follows:
Point 1: The base of the nasal ala on the normal noncleft side.
Point 2: The high point of the Cupid's bow on the noncleft side.
Point 3: The mid-point of the cupid's bow.
Point 4: The high point of the cupid's bow on the cleft side, determined by measuring the
distance between points 2 and 3.
Point 5: The peak of the cupid's bow on the lateral cleft segment, usually placed where
the white roll (vermilioncutaneous junction) begins to attenuate.
Point 6: The superior extent of the advancement flap. The distance between points 5 and
6 should be equal to the height of the lip in the noncleft side. Final determination of point
6 may have to wait until the rotation incision is completed in some cases.
Point 7: Located along the alar crease so that the distance between points 5 and 7 equals
the distance between points 1 and 2.
Point 8: The superior extent of the rotation incision, which may be extended to point 9 if
necessary, and should not cross the philtral column on the noncleft side.
Point 9: The extent of the backcut incision (if needed). This may be necessary to
achieve adequate downward rotation of the medial lip segment.
It should be emphasized that the initial markings as described are approximate and are
often modified as the operation proceeds.
The distance between points 1 and 2 represents the height of the lip on the noncleft side
and should equal the ultimate height of the lip on the cleft side; this measurement is also
useful as a guide in determining the length of the curvilinear incision between points 4
and 8. The position of this incision may be facilitated with the use of a curved 26-gauge
wire to mark an incision that begins at point 4 and ascends along the vermilioncutaneous
junction and then swings across the lip to where the columella meets the lip at point 8. It
is important that this line not extend or cross into the normal philtral column.
After marking and administration of a small amount of local anesthetic containing
epinephrine, the skin incisions are scored with a no. 63 Beaver blade and the cleft
mucosal flaps created. The other major incisions are then completed, beginning with the
rotation flap. Completion of the rotation incision allows point 4 to drop down to a
position symmetric with point 2; if the rotation still is not satisfactory, a 1-mm backcut to
point 9 may be performed to achieve satisfactory rotation. A small triangular flap of
tissue remains attached to the columella (Millard C flap), and this flap is later used for
lengthening the shortened columella of the cleft side or in the construction of the medial
aspect of the nasal sill. Final delineation of point 6 is now possible and is determined
after adequate downward rotation of point 4. If additional height is needed, point 6 may
be adjusted slightly into the nasal vestibule (avoid nasal vibrissae hairs) or point 5 may be
moved 1 to 2 mm lateral toward the oral commissure.
The medial and lateral lip flaps are freed by sharp dissection from the underlying maxilla
in a supraperiosteal plane only enough for a tensionless closure. Laterally this is
performed with a high gingivobuccal sulcus incision. Dissection is completed around the
nasal ala, intercartilaginous region, and piriform aperture as needed to release tension and
to allow for the nasal ala to be positioned independently of the lip.
Primary nasal reconstruction (if desired) is initiated by undermining the skin overlying
the columella, nasal dome, and lower lateral cartilages. The skin lining the vestibule is
elevated off the lateral crus of the lower lateral cartilage, thus freeing the lower lateral
cartilage from its attachments internally and externally. This allows it to be actively
repositioned within the skin pocket.
Depending on the individual case, the C flap may be advanced on itself, thus lengthening
the cleft side of the columella or used for the reconstruction of the medial portion of the
nasal sill. In many cases, it can be used for both columella and nasal sill reconstruction.
Suturing begins with placement of a 3.0 or 4.0 Vicryl (Ethicon, Cincinnati, OH) suture
that grasps the lip muscle back along the upper edge of the advancement flap and is
placed into the depths of the backcut rotation incision. This important suture sets the alar
base and determines the symmetry of the lip.
The orbicularis oris muscles are dissected about 1 to 2 mm from their attachment to skin
and mucosa, and then are approximated with interrupted 4.0 Vicryl sutures. After
placement of each stitch, overall symmetry of the lip is evaluated. If it is noted that there
is inadequate rotation, or insufficient length of the lateral segment, the sutures are
removed and adjustments made.
After muscular closure of the lip, the primary nasal reconstruction is completed. The
lower lateral cartilage is positioned and fixed into place with through-and-through 4.0
nylon sutures tied over Teflon pledgets. The nasal ala is positioned and fixed medially
with 4.0 Vicryl sutures. The skin and mucosa are approximated with 7.0 nylon or 6.0
chromic sutures, matching the vermilioncutaneous junction precisely. Final adjustment
of the vermilion is completed to create a tubercle, and any tendency toward vermilion
notching is corrected by creating a Z-plasty, with transposition of a mucosal flap from the
fuller side to the more deficient side to balance the lip. Nylon sutures are removed at 5 to
7 days on an outpatient basis with sedation. Nasal bolsters remain is place for 10 to 14
days.
Bilateral Cleft Lip Repair
Bilateral cleft lip repair is more complex that unilateral repair, but many of the principles
are the same (Fig. 80.6 and Fig. 80.7). The technique described here is as described by
Millard (6). A symmetric bilateral complete cleft lip and palate with an adequate and
moderately protruding prolabium and premaxilla is used as an example. Asymmetric
bilateral cleft lips and those with a rotated premaxilla are often treated with a two-stage
closure, using the lip adhesion as the first stage. For children with an extremely
protruding premaxilla, presurgical orthopedics may be required before definitive lip
repair to move the premaxilla posteriorly.

FIGURE 80.6. AI: Technique of bilateral cleft lip
repair.



FIGURE 80.7. A: Frontal preoperative view of bilateral
cleft lip. B: Lateral preoperative view of bilateral cleft
lip. C: Appearance of bilateral cleft lip repair 1 month
after procedure. Nasal columella reconstruction will be
performed at age 2 years.



As for the unilateral cleft lip repair, the initial step is to determine the lip landmarks
(6,11). Point 1 is the mid-point of the vermilioncutaneous junction of the prolabium (the
future low point of cupid's bow). From this point, both high points of the future cupid's
bow (points 2 and 3) are measured 2.5 to 3 mm on each side of point 1. Two slightly
curvilinear lines connect points 2 and 3 with points 4 and 5, which represent the junction
of the prolabium with the columella. This delineates the new philtrum. Two lateral
prolabial flaps (banked for future columella reconstruction) are used at this time to
construction the medial and inferior aspects of the nasal sill. Points 6 and 8 are marked at
the white line attenuation of the vermilioncutaneous junction on the lateral lip elements.
The distance from points 6 to 7 is designed to equal the distance from points 2 to 4; the
distance from point 8 to 9 is equal to the distance from point 3 to point 5. A vermilion
flap (6 to * and 8 to *) is created on each side, with the length of this flap approximating
the length of point 1 to point 2 and point 1 to point 3.
After the lip landmarks and incisions are marked, the lip is infiltrated with local
anesthetic containing epinephrine. The incisions are made with a no. 63 Beaver blade,
starting with the prolabium. The mid-prolabial flap (the future philtrum) and the two
lateral prolabial flaps are incised, pedicled superiorly, and dissected free of the
underlying premaxilla, along with a small vermilion flap (the e flap). The remaining
vermilion of the prolabium is dissected and pedicled inferiorly. The lateral lip incisions
and lateral vermilion flaps are then made and extended along the alar crease. The alae are
released from the underlying maxilla with dissection along the piriform aperture. Lateral
gingivobuccal sulcus incisions are created for further relaxation, and the lateral lip is
dissected from the underlying maxilla in the supraperiosteal plane, to allow adequate
mobilization of the orbicularis oris muscle to the midline.
The vermilion flap of the prolabium is sutured superiorly to mucosally line the anterior
premaxilla (Fig. 80.6C). The lateral lip mucosa is sutured at the midline with 4.0 chromic
suture and then the orbicularis oris muscle is advanced medially and sutured at the
midline with 4.0 Vicryl (Fig. 80.6E and Fig. 80.6F). The small vermilion flaps (which
will form the central vermilion tubercle of the lip positioned inferior to the philtrum) are
approximated with chromic sutures on the inner surface and 7.0 nylon sutures on the
external aspect of the vermilion. The central prolabial skin flap is fitted into position
between the lateral lip segments and sutured into place with 7.0 nylon, creating the
philtrum of the lip. The small e vermilion flap is tucked behind the lateral vermilion flaps
and contributes to creation of the central tubercle. The two lateral prolabial flaps are
banked into the region just inferior to the nares and sutured into position to assist with
nasal sill and floor reconstruction. These two banked flaps will ultimately be used to
reconstruct the columella in a secondary procedure.
Surgical Technique: Cleft Palate Repair
Many methods of cleft palate repair have been described (9,10,12,13 and 14). The
Wardill-Kilner-Peet technique (V-Y advancement), von Langenbeck technique, Bardach
two-flap technique, and Furlow technique (double reversing Z-plasty), as well as
modifications of each, are commonly used in the United States (12,14). The type of
palatoplasty used to close a cleft palate may be influenced by the width, position, and
extent of the cleft. Regardless of the procedure used, attention should be directed to
approximation and repair of the levator veli palatini muscle sling (known as intravelar
veloplasty) for improved velopharyngeal function.
Unilateral Cleft Palatoplasty
In the two-flap palatoplasty as described by Bardach (9), a single mucoperiosteal flap is
elevated from each palatal shelf, based posteriorly on the descending palatine artery. The
goals of the two-flap palatoplasty are complete two-layer mucosal closure (oral and
nasal) of the entire cleft, with dissection, redirection, and suturing of the soft palate
musculature (intravelar veloplasty) (Fig. 80.8).

FIGURE 80.8. AL: Unilateral cleft palatoplasty.



The cleft margins and adjacent mucoperiosteum as well as the soft palate posterior to the
maxillary tuberosity are infiltrated with local anesthetic with epinephrine. Starting at the
soft palate, the cleft edges are incised along the line dividing the nasal and oral mucosa to
the tip of the uvula. The cleft incisions on the hard palate are made about 1 to 2 mm
lateral to the cleft edge and connected with those on the soft palate. The lateral relaxation
incisions are completed, beginning about 1 cm posterior to and curving around the
maxillary tuberosity, then curving anteriorly inside the alveolus to join the medial
incision anteriorly.
Submucoperiosteal flaps are elevated from the hard palate bilaterally. The neurovascular
bundle containing the descending palatine artery in the greater palatine foramen is
identified and preserved. The posterior edge of the hard palate is identified and the
muscle fibers and mucosa dissected free.
The nasal mucoperiosteum from the nasal aspect of the hard palate is elevated at the cleft
edge. On the noncleft side, the nasal mucoperiosteum is elevated in a similar manner if
the vomer is not attached to the palatal shelf. If the vomer is attached to the palatal shelf,
a nasal mucoperiosteal flap is elevated off the vomer and kept continuous posteriorly
with the nasal mucosal layer of the soft palate. Within the soft palate, the muscle fibers
are dissected 1 to 2 mm from the nasal and oral mucosal edges, thus allowing the muscle
fibers to move from a previous anteriorposterior direction to a transverse orientation.
If medial mobilization of the mucoperiosteal flap is inadequate to create a tensionless
closure at the midline, these maneuvers may improve relaxation and decrease tension:
1. Blunt dissection in the plane between the superior constrictor muscle and
pterygoids (Space of Ernst)
2. Infracture of the hamulus and stripping of the tensor veli palatini muscle tendon
from its attachment to the hamulus
3. Further mobilization and dissection of the neurovascular bundle from the flap so
that it is attached only to the anterior half of the mucoperiosteal flap
After adequate mobilization of the oral mucoperiosteal flaps, velar musculature, and
nasal mucoperiosteum, the palate is closed in three layers. First, the nasal mucoperiosteal
edges are closed with 4.0 Vicryl sutures, beginning opposite the alveolus anteriorly and
continuing in a posterior direction to the tip of the uvula. All knots are placed on the nasal
side. Then, the velar muscles are approximated at the midline with several 3.0 Vicryl
horizontal mattress sutures. Finally, the oral mucoperiosteal flaps are closed, beginning at
the uvula and continuing anteriorly to the alveolus in an interrupted manner. The tips of
the flaps are sutured anteriorly, and the lateral relaxation incisions gently packed with
microfibrillar collagen.
Bilateral Cleft Palatoplasty
In bilateral cleft palatoplasty, the design of the incisions is similar to that of unilateral
cleft palatoplasty (Fig. 80.9), but bilateral vomer flaps are marked and used to close the
two nasal cavity layers. The remainder of the procedure is similar to the unilateral
palatoplasty.

FIGURE 80.9. AJ: Bilateral cleft palatoplasty.



Palatoplasty for Clefts of the Secondary Palate
Two effective methods are available for closure of clefts of the secondary palate: the
Wardill-Kilner V-Y advancement (12) and the Furlow double reversing Z-plasty (14).
The former procedure is more suitable for clefts extending into the hard palate and for
wide clefts. The Furlow Z-plasty is an excellent procedure for the narrow soft palate cleft
and the submucous cleft palate. Both procedures are described.
In the Wardill-Kilner or V-Y advancement (Fig. 80.10), the oral mucoperiosteal flaps are
designed so that the tips of the flaps are opposite the primary canine teeth. Oral and nasal
mucoperiosteal flaps are elevated in a similar fashion as in the unilateral palatoplasty,
including vomer flaps if there is extension of the cleft into the hard palate. The velar
musculature is freed from its attachments to the posterior border of the hard palate. The
closure is similar, with careful attention to the intravelar veloplasty as previously
described. The lateral relaxation incisions may be packed with microfibrillar collagen.
The soft palate is lengthened upon itself with the V-Y advancement.

FIGURE 80.10. AF: Palatoplasty for a cleft of the
secondary palate, V-Y advancement.



The Furlow palatoplasty (Fig. 80.11) uses a different approach than the previously
described techniques. This procedure lengthens the soft palate with a Z-plasty, and
overlapping the mucomuscular flaps realigns the levator sling.

FIGURE 80.11. Palatoplasty for a cleft of the secondary
palate, Furlow double opposing Z-plasty.



The flaps on the oral mucosa are first outlined as diagrammed with a vital dye. The
operation as described is designed for the right-handed surgeon (left-handed surgeons
would be advised to reverse the orientation of the incisions to facilitate flap dissection).
The solid lines indicate the oral mucosal incisions. After infiltration of the soft palate
with local anesthetic containing epinephrine, the cleft margins are incised, or, in the case
of a submucous cleft, the midline is incised to create an overt cleft palate. The left side
oral mucosal incision is made down to the muscles. The soft palate musculature is then
bluntly separated from the nasopharyngeal mucosa and from the posterior border of the
hard palate. Using angled scissors, the lateral limb of the opposing (nasopharyngeal
mucosa) Z-plasty is made, corresponding to the broken line in Fig. 80.11.
The oral mucosal flap on the right side is incised (solid line), just through the mucosa and
submucosa. The flap is developed in a plane between the submucosa and the soft palate
musculature. The muscle is dissected away from the posterior border of the hard palate.
The nasopharyngeal flap incision is made with angled scissors (broken line) such that the
muscles are included with the nasopharyngeal flap.
At this point, after flap interdigitation, there are two anteriorly positioned mucosal flaps
and two posteriorly positioned mucomuscular flaps. The nasopharyngeal flaps are
transposed and closed using 4.0 Vicryl and 4.0 chromic sutures in an interrupted fashion
with the knots placed on the nasal side. The oral layer flaps are transposed and sutured
similarly. The overlapped mucomuscular flaps can be sutured to each other with
absorbable sutures. If necessary, the tips of the incisions may be closed upon themselves
to prevent excess tension.
The Furlow palatoplasty is being combined increasingly with the previously described
unilateral and bilateral palatoplasty procedures as the treatment for the soft palate. It is
advisable that combination be considered if the soft palate is short or if the cleft is fairly
narrow. The distinct advantage of using this technique on the soft palate is the increase in
length of the soft palate resulting from the Z-plasty. On the other hand, there is increased
operative time, dissection, and scarring within the soft palate, and increased risk of fistula
at the junction of the hard and soft palates.
When the Furlow palatoplasty is used in conjunction with a unilateral or bilateral
palatoplasty, the incisions are marked with a vital dye after infiltration of the palate with
a local anesthetic containing epinephrine. The mucoperiosteal flaps are first raised as
previously described, and the viability and vitality of the greater palatine artery is
assessed prior to proceeding with the Furlow soft palate incisions. If there is any concern
about the vascular pedicle, the procedure continues as the standard unilateral or bilateral
palatoplasty, without the Furlow modification. Aspects of the closure are similar to those
as previously described. The Furlow nasopharyngeal flaps are interdigitated and closed in
continuity with the nasal cleft edges in the hard palate region. Interdigitation and
approximation of the Furlow oral mucomuscular flaps are made in continuity with the
oral mucoperiosteal flaps. Attention should be directed to minimize the tension at the
junction of the hard and soft palate, because this is the region of highest risk of fistula
formation.
CONCLUSION
This chapter has presented an overview of the initial and primary care required for the
child born with a cleft lip and palate. The surgical techniques described are usually
completed within the first year of life. In most cases, further therapeutic intervention will
be required via the cleft palate team approach that may include surgical correction of
secondary cleft lip and nasal deformities, otologic and audiologic care, dental and
orthodontic management, and speech therapy services.

HIGHLIGHTS
Cleft lip and palate is the most common congenital
malformation involving the head and neck, and a cleft palate
team approach best provides long-term multidisciplinary
management.
Cleft lip and palate occurs in 1 in 1,000 births; cleft palate alone
occurs in 1 in 2,000 births. Clefts occur in children with
recognizable syndromes or as an isolated deformity
(nonsyndromic).
Lip and palate embryologic development occurs in two phases:
the first beginning at 4 to 5 weeks (lip, nose, premaxilla) and
the second beginning at 8 to 9 weeks (secondary palate).
The relative prevalence of cleft types include complete cleft lip,
alveolus, and palate, 45%; cleft lip with or without cleft
alveolus, 25%; and clefts of the secondary palate only, 30%.
Critical psychosocial and nutritional issues should be addressed
in the neonatal period.
The infant is discharged home from the newborn nursery only
after a satisfactory feeding method has been established and the
parents are capable and comfortable caring for the infant.
Lip adhesion is an early preliminary repair option for cleft lip
and may be performed at 2 to 4 weeks of age. Definitive lip
repair is then performed at 4 to 6 months of age. Lip adhesion
may influence scar formation and is used in carefully selected
cases.
The rule of tens is used to determine suitable age for lip repair:
the infant is at least 10 weeks old, weighs about 10 pounds, and
has a hemoglobin of 10 g.
Cleft palate repair is usually performed at 9 to 12 months of age
as long as the child is gaining weight and growing in a normal
fashion.
In many cases, ongoing evaluation and management will be
needed and determined by the cleft palate team members. This
may include surgical correction of secondary lip and nasal
deformities, dental and orthodontic care, speech therapy (for
both treatment and assessment for articulation errors,
compensatory errors and velopharyngeal incompetence),
routine otologic and audiologic care, and orthognathic surgery.
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736.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

81 TONSILLITIS, TONSILLECTOMY, AND ADENOIDECTOMY
Head & Neck SurgeryOtolaryngology
81




TONSILLITIS, TONSILLECTOMY, AND
ADENOIDECTOMY
LINDA BRODSKY
CHRISTOPHER POJE

L. Brodsky and C. Poje: Department of Otolaryngology and Pediatrics, State University of New York at
Buffalo, School of Medicine and Biomedical Sciences, and Department of Pediatric Otolaryngology,
Children's Hospital of Buffalo/Kaleida Health, Buffalo, New York.


Anatomy
Adenoids
Tonsils
Microbiology and Immunology
Microbiology
Immunology
Pathogenesis of Adenotonsillar Disease
Clinical Classification of the Adenoids and Tonsils
Adenoids
Tonsils
Clinical Evaluation
Adenoids
Tonsils
Management of Diseases of the Adenoids and Tonsils
Adenoids
Tonsils
Peritonsillar Abscess
Lingual Tonsils
Unilateral Tonsil Hyperplasia
Chapter References
Health problems from disease in the tonsils and adenoids are among the most commonly
encountered in the general population. Complaints of sore throat, upper respiratory
infection, and associated ear disease account for the greatest number of patient visits in
most primary care settings dealing with children. Although the incidence of tonsillectomy
and adenoidectomy is decreasing, even in the face of an increasing population base, it
remains the most commonly performed major surgical procedure in children in the
United States.
The otolaryngologist plays a critical role in management and must understand basic
anatomy, physiology, clinical presentation of both adenoid and tonsillar pathology,
medical therapy options, and appropriate patient selection for surgical intervention.
Principles of surgical management (preoperatively, intraoperatively, and postoperatively)
are changing rapidly, and the otolaryngologist needs to be aware of those strategies that
help to expedite recovery and minimize complications. Precise clinical assessment is
particularly important given the scope and nature of problems encountered in children,
who are most often affected.
Recurrent and chronic infection and obstructive hyperplasia are the most common
diseases affecting the tonsils and adenoids in the pediatric population. Peritonsillar
abscess (PTA) is a frequent presentation of tonsil disease, which requires a separate
discussion. Unusual infections of the tonsils (e.g., mycobacterial), neoplastic processes
(most commonly lymphomas), and disease in the lingual tonsils also may occur and are
discussed separately.
ANATOMY
Adenoids
The adenoids (pharyngeal tonsils) are a triangular mass of lymphoid tissue located on the
posterior aspect of the boxlike nasopharynx (Fig. 81.1). The nasopharynx serves as a
conduit for inspired air and sinonasal secretions that drain from the nasal cavity into the
oropharynx, a resonance box for speech, and a drainage area for the eustachian tube
middle earmastoid complex. Formed during the 3rd to 7th months of embryogenesis,
they are present at birth and become colonized with bacteria during the first few weeks of
life. Enlargement during early and middle childhood occurs in response to a variety of
antigenic challenges, which may include viruses, bacteria, allergens, foods, and
environmental irritants. In most instances, the adenoids regress during puberty and early
adulthood.

FIGURE 81.1. The adenoids are situated in the posterior
wall of the nasopharynx. The paranasal sinuses
(anteriorly) and the eustachian tubemiddle earmastoid
complex (laterally) drain into this space, which connects
the nose to the nasopharynx. The tonsils are located on
the lateral walls of the oropharynx and extend from the
lateral edges of the soft palate to the base of the tongue.



The anatomic relationship between the nasopharynx and the adenoids has implications
for disease in the laterally located eustachian tubemiddle ear complex and anteriorly
located nose and paranasal sinuses. Both functional and mechanical obstruction of the
eustachian tube with adenoid inflammation play a significant role in the development of
middle ear disease (1,2). In younger children, adenoid enlargement and chronic infection
are also significant in recurrent and chronic sinusitis (3).
In children with normal craniofacial skeletons, nasopharyngeal obstruction results from
adenoids that have become too large for a normally sized nasopharynx. Two-dimensional
lateral neck radiographs, with their inherent limitations in depicting a three-dimensional
space, are still used to assess this relationship. Investigators have reported both small and
normal-sized nasopharyngeal spaces in children with obstruction (4).
Blood is supplied to the adenoids via the pharyngeal branches of the external carotid
artery; some minor branches contribute from the internal maxillary and facial arteries.
Sensory innervation is received from both the glossopharyngeal and vagus nerves.
Therefore, referred pain from the adenoids (as well as the tonsils) may be perceived in
both the ears and throat.
The gross and microscopic anatomy of the adenoids reflects their many functions and
differs significantly from that of the tonsils. The adenoids are invaginated by deep folds,
with some crypt formation, in marked contrast to the extensive system of crypts found in
the tonsils. Adenoids have three types of surface epithelium: ciliated pseudostratified
columnar, stratified squamous, and transitional (Table 81.1). Chronically infected or
enlarged adenoids tend to have an increased proportion of the specialized squamous
epithelium (active in antigen processing) and a decreased proportion of the respiratory
epithelium (active in mucociliary clearance). The stasis of sinonasal secretions that
accompanies the nasal obstruction results in an increased exposure to antigenic stimuli,
resulting in chronically inflamed, nonfunctioning adenoids (5).

TABLE 81.1. ANATOMIC AND PHYSIOLOGIC
DIFFERENCES BETWEEN THE ADENOIDS AND
TONSILS



Tonsils
The (faucial or palatine) tonsils are paired, generally ovoid masses located on the lateral
walls of the oropharynx (Fig. 81.1 and Fig. 81.2). Although usually confined to the
oropharynx, with excessive growth the tonsils may extend up into the nasopharynx,
presenting with velopharyngeal insufficiency or nasal obstruction. More commonly, they
grow to extend down into the hypopharynx, presenting with a pattern of obstructive sleep
(and awake) breathing disturbances. Their anatomic location makes them less likely to be
associated with disease of the eustachian tubemiddle ear complex and the sinuses;
however, the tonsils and adenoids often are affected simultaneously by similar disease
processes: chronic/recurrent infection and/or obstructive hyperplasia. This challenges the
clinician's ability to assess the precise anatomic location(s) causing the problem.

FIGURE 81.2. Although the tonsils generally are
confined to the oropharynx, they may by bilobed with
extension into the hypopharynx or more rarely into the
nasopharynx. Inferior extension of the tonsils should be
suspected when a strong history of obstruction with
relatively normal-appearing tonsils are visualized on
intraoral examination.



Tonsillar hyperplasia may cause an abnormal tongue position, a tongue-thrust habit,
aberrant speech patterns, and altered orofacial growth. Similar to the adenoids, the
relationship between the volume of the oropharynx, the size of the tonsils, and the
etiology of the upper airway obstruction is multifactorial but appears to be related to both
the tonsillar hyperplasia and an anatomically smaller oropharynx.
The deep surface of the tonsil is attached to the fascia overlying the superior constrictor
muscle. Its anterior boundary is the palatoglossus muscle (anterior pillar), and its
posterior boundary is the palatopharyngeus muscle (posterior pillar). The tonsil may
extend inferiorly to become continuous with lingual tonsillar tissue at the base of the
tongue.
The tonsils are supplied by the ascending pharyngeal, ascending palatine, and branches
from the lingual and facial arteries, all branches of the external carotid artery. The
internal carotid artery lays approximately 2 cm posterolateral to the deep aspect of the
tonsil; thus, care must be taken to stay in the proper plane of dissection to avoid injury to
an aberrantly located vessel. The lymphatic drainage from the tonsils is primarily into the
superior deep cervical and jugular lymph nodes; thus, inflammatory disease in the tonsils
is a significant factor in the development of cervical adenitis/abscess in children. Sensory
innervation is from the glossopharyngeal nerve and some branches of the lesser palatine
nerve via the sphenopalatine ganglion.
The histologic structure of the tonsils is closely related to its apparent function as an
immunologic organ. The tonsils (and adenoids) have no afferent lymphatics, but the 10 to
30 cryptlike invaginations that branch deep into the tonsil parenchyma and are lined by
the specialized antigen processing squamous epithelium serve as the immune system's
access route for both inhaled and ingested antigens. The crypt epithelium has a complex
system of specialized antigen-presenting cells and micropores that deliver the antigen to
the immunologically active lymphoid cells underlying the tonsillar epithelium. Four
zones (or compartments) that are important in antigen processing have been described:
specialized squamous epithelium, extrafollicular area (T cellrich area), mantle zone of
the lymphoid follicle, and the germinal center of the lymphoid follicle (B cells). Antigen
processing in relation to the functional anatomy is described in the following section on
immunology.
MICROBIOLOGY AND IMMUNOLOGY
The microbiology and immunology of the tonsils and adenoids are similar and therefore
will be discussed together.
Microbiology
Group A -hemolytic streptococcus (GABHS) is classically described as the only
bacterium implicated frequently in acute tonsillitis. The readily detectable systemic
antibody response that occurs after GABHS infection forms the basis of this belief;
however, an extensive body of evidence is mounting for the role of other aerobic and
anaerobic microorganisms in the development of both acute and chronic tonsil and
adenoid disease (6,7) (Table 81.2). The bacteria encountered are remarkably similar to
those found in otitis and sinusitis.

TABLE 81.2. BACTERIA AND VIRUSES
COMMONLY CULTURED FROM THE TONSILS
AND ADENOIDS



Several new concepts have emerged in the understanding of chronic adenotonsillar
disease and include (a) the presence of polymicrobial infections (8), (b) the increased
presence of -lactamaseproducing microorganisms, (c) the role of anaerobes (9), (d) the
role of bacterial antigenic concentration, (e) the presence of Haemophilus influenzae, (f)
the importance of crypt obstruction resulting in bacterial stasis and the establishment of
chronic infection, and (g) the disruption in normal bacterial homeostasis shifting from
commensals to potential pathogens.
An exclusively viral etiology as the basis for chronic disease is unlikely, although
viruses, as initiators of mucosal inflammation, crypt obstruction, and ulceration with
secondary bacterial invasion and infection, are likely to activate the acute infection.
Epstein-Barr virus (EBV) infection may present as a serious acute pharyngotonsillitis,
even at times with airway obstruction. EBV also may be associated with persistent
adenotonsillar hyperplasia. The role of both acid and alkaline gastric refluxate
(extraesophageal reflux) as an inciting event in the development of cryptitis is being
actively investigated.
Immunology
The immunology of the tonsils and adenoids is a complex and challenging topic. A
complete review of the subject is beyond the scope of this text; however, excellent
reviews are available to the interested reader (10). Certain aspects of the immunology of
these organs have specific clinical implications that are discussed herein.
The tonsils and adenoids are unique insofar as they are involved in both local immunity
and in immune surveillance for the development of the body's immunologic defense
system. Chronic bacterial infection (and other ongoing antigenic stimulators) in the
tonsils and adenoids may result in the production of local antibody, a shift of B- and T-
cell ratios, and, according to some researchers, an increase in the serum immunoglobulin
levels, which return to normal after tonsillectomy and adenoidectomy. In contrast to
proper lymph nodes, the tonsils and adenoids have no afferent lymphatics; therefore, their
specialized epithelium plays an important role in antigen presentation and processing.
This is followed by both T- and B-cell responses, including immunoglobulin production,
expansion of memory clones, and hyperplasia.
The effects of adenotonsillectomy on the patient's immunologic integrity are widely
debated. Reports of reduced nasopharyngeal immunoglobulin A (IgA) production against
polio vaccine after adenoidectomy or an increase in Hodgkin's lymphoma after
tonsillectomy and adenoidectomy have been found to be either clinically insignificant or
unsubstantiated by in-depth epidemiologic studies. Although no specific adverse effects
have been documented after their removal, these organs of general immune
surveillance provide an immune function not easily dismissed. Therefore, the tonsils and
adenoids should be removed only for clearly defined clinical disease.
PATHOGENESIS OF ADENOTONSILLAR DISEASE
The pathogenesis of infectious and inflammatory disease in the tonsils and adenoids most
likely has its basis in their anatomic location and their inherent function as organs of
immunity, processing infectious material and other antigens, and then becoming,
paradoxically, a focus of infection or inflammation. However, no single theory of
pathogenesis has been accepted. Viral infection with secondary bacterial invasion may be
one mechanism of the initiation of chronic disease, but the effects of the environment,
host factors, the widespread use of antibiotics, ecological considerations, and diet all may
play a role.
Recent work reveals that inflammation and loss of integrity of the crypt epithelium result
in chronic cryptitis and crypt obstruction, leading to stasis of crypt debris and persistence
of antigen. Bacteria even infrequently found in normal tonsil crypts may multiply and
eventually establish chronic infection.
CLINICAL CLASSIFICATION OF THE ADENOIDS AND TONSILS
The clinical classification of diseases in the adenoids and tonsils must be defined
precisely to allow effective communication between the otolaryngologist and the
referring primary care physician. Recognizing the specific disease process and the
difficulties encountered with each diagnosis allows the otolaryngologist not only to guide
medical therapy but also to select appropriate candidates for surgery. One suggested
classification system is presented in Table 81.3.

TABLE 81.3. CLINICAL CLASSIFICATION OF
DISEASE IN THE TONSILS AND ADENOIDS



Inflammation of the adenoids and tonsils may be induced from environmental irritants,
allergens, or extraesophageal gastric reflux. Until recently, the inflammatory process seen
in the tonsils was believed to be almost exclusively a viral-bacterial phenomenon, but
reevaluation of this scenario is under way.
Adenoids
Acute Adenoiditis
The diagnosis of acute adenoiditis is particularly difficult to differentiate from a
generalized virally induced upper respiratory infection (URI) or a true bacterial
rhinosinusitis. Purulent rhinorrhea, nasal obstruction, fever, and often otitis media may be
seen. When the acute infection is accompanied by loud snoring, which then dissipates
after the episode, infection in the adenoids may be more likely. The child also may have a
lingering course and appear sicker than when confronted with a typical viral URI.
Recurrent Acute Adenoiditis
Recurrent acute adenoiditis is defined as the presence of four or greater discrete episodes
of acute adenoiditis during a 6-month period. As with otitis, if the child is asymptomatic
between infections, a role for antimicrobial prophylaxis may be considered, especially if
comorbidity occurs (i.e., reactive airway disease, recurrent otitis). With emerging
antibiotic resistance, the decision to treat with prophylactic antibiotics must be made
cautiously. Either daily low-dose (one half to one third the full dose) or episodic
prophylaxis (short course of antibiotics with the onset of an upper respiratory infection)
may be effective. Differentiating between recurrent acute sinusitis and recurrent acute
adenoiditis may be extremely difficult to make on clinical grounds alone (11).
Radiographs to evaluate the sinuses may be useful. Extraesophageal reflux (EER)-
induced adenoiditis, especially in children under 1 year of age, must be considered
(unpublished data).
Chronic Adenoiditis
Persistent nasal discharge, malodorous breath, postnasal drip, and chronic congestion
may signify a chronic adenoid infection. Because most of these symptoms also are often
associated with chronic sinusitis, differentiating between the two is clinically challenging.
The association of otitis media may be more indicative of chronic adenoiditis, but otitis
also is found in association with sinusitis, although less frequently. The role of EER as
contributory to chronic adenoid inflammation, especially in younger children, is
becoming increasingly evident (12). In patients with unremitting disease, a thorough
evaluation for EER is warranted.
Obstructive Adenoid Hyperplasia
The triad of symptoms, including chronic nasal obstruction (associated with snoring and
obligate mouth breathing), rhinorrhea, and a hyponasal voice, are most consistent with
nasopharyngeal obstruction by enlarged adenoids.
Tonsils
Acute Tonsillitis
Sore throat, fever, dysphagia, and tender cervical nodes in the presence of tonsils that are
erythematous and have exudates is consistent with a diagnosis of acute tonsillitis. Not all
these signs and symptoms are present in every patient; unfortunately, many clinicians
have come to rely on the presence of a positive throat culture or rapid-Strep antigen test
for GABHS as the sole criterion to diagnose acute tonsillitis. In the ill child with clearly
inflamed tonsils, other bacterial causes or EBV infection (infectious mononucleosis) also
should be considered and treated when appropriate. The wide range of accuracy in the
clinical diagnosis of acute tonsillitis must be kept in mind when making surgical
recommendations.
Recurrent Acute Tonsillitis
Recurrent acute infection has been variably defined as four to seven episodes of acute
tonsillitis in 1 year, five episodes for 2 consecutive years, or three episodes per year for 3
consecutive years (13,14).
Chronic (Persistent) Tonsillitis
Chronic sore throat, malodorous breath, excessive tonsillar debris (tonsilloliths),
peritonsillar erythema, and persistent, tender cervical adenopathy are consistent with a
diagnosis of chronic tonsillitis when no other source (such as the sinuses or lingual
tonsils) can be identified.
Obstructive Tonsillar Hyperplasia
Enlarged tonsils can cause snoring, with obstructive disturbances (asleep and awake),
dysphagia, and voice changes (muffling or hyponasality). Enlarged tonsils, by
themselves, in the absence of identifiable symptoms that affect the child's health and
well-being, need not be removed automatically.
Both benign and malignant neoplastic disease can occur in the tonsils and adenoids.
Unilateral tonsillar hyperplasia should always raise this suspicion. The presence of
adenoids in an older teenager also should be investigated for malignancy.
CLINICAL EVALUATION
Adenoids
Differentiating acute and chronic infection in the adenoids from that in the sinuses is a
particular challenge because both infections present with symptoms of rhinorrhea, cough,
and postnasal drip. Therefore, a complete ororhinolaryngologic examination, sometimes
including nasopharyngoscopy or sinus radiography, is necessary. The coexistence of
these two problems (with the chronic adenoid infection leading to a secondary sinusitis or
the reverse) depends on the clinician's viewpoint. When medical therapy fails, however,
adenoidectomy is the first step in controlling infection in the nose/nasopharynx; about
67% of children show resolution. Preoperatively, parents should be made aware that if
symptoms do persist after adenoidectomy, further investigation and treatment of the sinus
disease might be necessary. It is not unusual for the sinusitis to take 2 to 3 months to
clear after the adenoids are removed (11).
Obstructive adenoid hyperplasia is best diagnosed by clinical history and physical
examination. The previously mentioned triad of obligate mouth breathing (both awake
and asleep), snoring, and hyponasal speech is seen. Rhinorrhea, postnasal drip, and
chronic cough (especially nocturnal) are common but nonspecific and, when present,
must be differentiated from allergic and nonallergic rhinitis, EER, and sinusitis.
Associated symptoms of obstructive sleep disturbances (discussed fully under the ensuing
subsection on Tonsils) must be sought.
The presence and severity of these symptoms should be confirmed by the physical
examination. Because several pathologic processes may coexist, clinical judgment plays
an important role. The classic adenoid facies characterized by an open mouth
appearance, flattened mid-face, and dark circles under the eyes is also seen in children
with allergic rhinitis or other causes of chronic nasal obstruction. Abnormalities in the
maxillarymandibular relationship may be identified, but the cause and effect of chronic
nasal obstruction cannot be assumed. Therefore, unless nasal obstruction is or has been
clearly present, the malocclusion alone may not be sufficient reason to remove the
adenoids.
The nasality of speech is assessed by having the child repeat words that emphasize nasal
emission such as milkman or Mickey Mouse and comparing them with words that do not,
such as baseball. Another method to assess is to pinch the nose during a nasally
transmitted phrase and assess the degree of change when released. Loss of appropriate
nasality further supports the diagnosis of obstructive adenoid hyperplasia when the
intranasal examination is otherwise normal.
The physical examination should include both anterior and posterior rhinoscopy. Anterior
rhinoscopy using the otoscope with either the nasal speculum attachment for older
children or a large-ear speculum for younger children is an excellent way to visualize
with magnification the interior of the nose. It is readily available and familiar to the child,
resulting in improved compliance with the examination. The nasal mucosa, presence and
location of secretions (sometimes after decongestion), and status of the nasal septum are
evaluated. Children with obstructive adenoid hyperplasia often will have normal-
appearing nasal mucosa; however, when the turbinates are enlarged and a nasal discharge
is present, gentle suctioning after the application of a topical decongestant can help to
differentiate anterior from posterior obstruction. In children 3 years of age and older,
direct flexible fiberoptic nasopharyngoscopy may help in establishing a diagnosis.
When typical signs and symptoms of obstructive adenoid hyperplasia are noted, a lateral
neck radiograph is unnecessary to confirm a clinically apparent diagnosis. Lateral neck
films are limited by the two-dimensional representation of a three-dimensional space and
by unreliability in demonstrating small amounts of obstructing adenoid tissue or stasis of
mucous secretions (from functionally significant but not totally obstructing adenoids)
blocking the posterior choanae. Improper positioning or poor patient cooperation can
affect the results of the radiograph. Radiographs may be helpful when the symptoms and
physical examination are not in agreement or as part of a sinus series when looking for
the presence of concomitant sinus disease.
The objective assessment of recurrent acute or chronic infection is much more difficult.
Eliminating other diagnoses, such as nasal mucosal disease and sinusitis, is necessary.
The child should be evaluated for allergies when signs of sneezing, itchy eyes, and skin
sensitivities are present. Sometimes serial evaluations of a patient by the otolaryngologist
when an acute infection is present may be necessary to clarify a diagnosis. When
nocturnal cough, throat clearing, and burping are present, EER should be investigated.
Palate evaluation should be part of every otolaryngologic evaluation, particularly when
adenoid surgery is contemplated. Palatal abnormalities, such as an occult or overt
submucous cleft palate, may mimic or may be masked by adenoid hyperplasia. If these
problems are not identified before surgery, hypernasal speech from velopharyngeal
insufficiency (VPI) may result. Speech therapy and secondary surgical or prosthetic
management may be required to correct this problem. A bifid uvula, abnormal motion of
the palate, midline diastasis of the muscles, history of fluid regurgitation through the
nose, or a family history of insufficiency or clefting should prompt nasopharyngoscopic
evaluation of the palate before undertaking adenoidectomy. At nasopharyngoscopy, loss
of the midline bulge seen on evaluation of the palate signifies the absence of the
musculus uvulae, associated with a higher risk of development of VPI postoperatively.
Children with neuromuscular and central nervous system (CNS) problems are also at
increased risk for VPI following adenoidectomy.
Tonsils
Acute tonsillitis is the most common manifestation of tonsillar disease. It is most often
treated in the primary care physician's office and is associated with sore throat,
dysphagia, fever, and tender cervical adenopathy. The tonsils may appear normal-sized or
enlarged but are usually erythematous. Often, but not always, an exudate can be seen.
Close inspection of the crypts will reveal inspissated material obstructing them.
Unfortunately, many practitioners use the presence of GABHS on throat culture as the
sole criterion for the diagnosis of acute tonsillitis; however, most clinicians treat with
antibiotics before the results of the culture are known. Even in the absence of a positive
culture for GABHS, a clear benefit is often seen by the patient, parent, and physician, in
which case antibiotics are usually continued. Acute tonsillitis may cause significant
morbidity for the patient and family; however, apart from PTA and cervical adenitis with
abscess, significant complications are rare. These include poststreptococcal
glomerulonephritis and rheumatic fever.
When the otolaryngologist sees the patient, the acute phase usually has subsided and the
physical examination may not be as helpful as the history in determining the presence of
recurrent acute or chronic infection. The tonsils may appear normal, or there may be
more subtle signs of chronic disease, such as peritonsillar erythema; enlarged, tender
cervical nodes; small tonsilloliths; or a decrease in the expected number of tonsillar
crypts, with a smooth glistening surface seen on the tonsils. Relying solely on the history
given by the family may overestimate or underestimate the severity of disease; therefore,
when records are unavailable for documentation and the physical examination is entirely
normal, serial examinations of the patient to document the frequency and severity of
infection are appropriate.
Obstructive tonsillar hyperplasia is currently the most common reason for tonsillectomy.
These patients present with varying degrees of obstructive sleep and awake breathing
disturbances, which may include symptoms of loud snoring (accompanied by periods of
irregular breathing), nocturnal choking and coughing, frequent awakenings with restless
sleep, dysphagia, daytime hypersomnolence, and behavioral changes. The most seriously
affected patients may present with failure to thrive or congestive heart failure from cor
pulmonale, but these are rare. Children at particular risk for the development of
obstructive sleep (or awake) disturbances secondary to tonsillar hyperplasia include those
with craniofacial anomalies, Down syndrome, or neuromuscular or CNS abnormalities.
These children may present with a smaller amount of tonsil and adenoid tissue but still
experience a considerable degree of obstruction.
The examination should be done with the child's mouth open and the tongue lying on the
floor of the mouth. Using two tongue depressors to depress the anterior tongue gently
will almost always keep the child from gagging. Gagging and tongue extrusion cause the
tonsils to come medially and give a false impression of enlargement (Fig. 81.3). The
inferior extent of the tonsils must be evaluated carefully, because the hypopharyngeal
area may not be seen clearly on intraoral examination. Having the child phonate aaah
may allow visualization of the inferior extent of the tonsils and provide an opportunity for
examination of palatal elevation.

FIGURE 81.3. The tonsils are examined with the tongue
lying on the floor of the mouth and two tongue depressors
gently pressing down anterior to the circumvallate
papillae, thereby preventing gagging associated with
medialization of the tonsils and a false impression of
obstructive tonsillar hyperplasia.



A standardized record of the clinical examination of the tonsils is strongly recommended
(Fig. 81.4). Often, but not always, obstructive hyperplasia occurs in both the tonsils and
adenoids, and then they should be removed simultaneously. A dilemma occurs when
adenoid obstruction is apparent and the tonsils are +1 or +2. In these cases, clinical
judgment plays a substantial role. Unless significant (+3 or +4) hyperplasia of the tonsils
is seen, the tonsils should be left in situ, particularly in the older child who may soon
grow into his or her tonsils and when there is no history of recurrent or chronic tonsil
infection. Sometimes it is difficult to explain this rationale to parents who have been told
that the tonsils might as well be removed while you are in there. The significantly
increased morbidity and surgical risk from tonsillectomy must be carefully explained in
these instances. As stated previously, in children with abnormal structure of their airway
or with neuromuscular disease, lesser degrees of tonsillar enlargement may be
problematic.

FIGURE 81.4. A standardized grading classification is
proposed based on the ratio of the tonsils to the
oropharynx (in the medial to lateral plane) as measured
between anterior pillars. 0, tonsil in fossa; +1, <25% of
tonsils occupy oropharynx; +2, >25%, <50%; +3, >50%,
<75%; +4, >75%. The narrowest portion of the airway
should be used, and the anatomic location of this point
should be noted as described in Fig. 81.5. This classification does not take into account
the anterior to posterior space. An increase in this space in some children may account for
the occasionally noted asymptomatic massive tonsillar hyperplasia.



Multichannel polysomnography (PSG) is considered the gold standard in the diagnosis of
obstructive sleep apnea (OSA). Normative PSG data has been established for children
that explains why the pediatric definition of OSA is different from the adult one (16). A
consensus statement from the American Thoracic society states that an obstructive apnea
of any duration should be scored (17). An apnea index of greater than one event per hour
is statistically significant; however, the clinical significance has not yet been ascertained.
Because children with obstructive sleep apnea frequently have persistent hypopneas with
hypoventilation rather than clear-cut obstructive apneas, it is also important to measure
the peak end-tidal CO
2
. An elevated end-tidal CO
2
indicates that hypoventilation is
present (16). It is highly impractical and costly for every child with enlarged tonsils and
obstructive symptoms to undergo a sleep study prior to an adenotonsillectomy. In a child
in whom the diagnosis is unclear or who has an unusual risk for surgery, PSG should be
performed. An audiotape or videotape of the child's sleep recorded by the parents may be
helpful if it demonstrates sounds or behavior consistent with obstruction; however, these
are nonvalidated tests that are likely to miss significant disease or underestimate the
severity of a life-threatening obstruction. Table 81.4 summarizes the clinical evaluation
of the tonsils and adenoids.

TABLE 81.4. CLINICAL EVALUATION OF
ADENOIDS AND TONSILS



MANAGEMENT OF DISEASES OF THE ADENOIDS AND TONSILS
In the past, the usual approach to disease in the adenoids and tonsils has been surgical
removal. The role of chronic infection, the presence of chronic cryptitis, alterations in the
relationship with commensal microorganisms, and a greater understanding of the role of
the tonsils and adenoids in both local and systemic immunity have led to a reevaluation
of this approach. Careful patient evaluation and the judicious use of antibiotics and
consideration of newer approaches to treatment of disease in the tonsils and adenoids will
continue to contribute to the decreasing number of tonsillectomies and adenoidectomies
performed each year.
Adenoids
Recurrent or chronic adenoiditis should be treated initially with an antimicrobial effective
against -lactamaseproducing microorganisms, particularly when associated with
persistent or recurrent otitis media or sinusitis. Adenoid hyperplasia also may respond to
a 6- to 8-week course of intranasal steroids, but long-term results are as yet unknown.
The indications for adenoidectomy are listed in Table 81.5. Before surgery, a thorough
past medical history should be taken (see discussion of preoperative evaluation under
following subsection on Tonsils).

TABLE 81.5. INDICATIONS FOR
ADENOIDECTOMY
a




Many surgical techniques have been advocated for adenoidectomy. Currently accepted
techniques include mirror visualization of the nasopharynx and removal of the tissue with
a sharp curette, adenotome, powered microdebrider, or with cautery. Some controversy
surrounds what is complete removal of the adenoids and whether the area around the
eustachian tube should be operated on vigorously. We prefer to do an almost complete
adenoidectomy with curette, leaving the area of the eustachian tube relatively untouched
so as to avoid postoperative scarring and possible permanent eustachian tube dysfunction.
Great care also should be taken at the posterior choanae so that stenosis does not occur in
that region from overzealous surgery and subsequent scarring. With direct visualization
of the nasopharynx, these problems usually can be avoided. Hemostasis may be
accomplished with intraoperative packing alone, application of bismuth subgalleate, or
electrocoagulation of the adenoid bed.
Palatal clefting and velopharyngeal insufficiency are relative contraindications to
adenoidectomy; however, if significant obstructive sleep apnea is documented by
polysomnogram, a carefully executed lateral or superior adenoidectomy may suffice to
relieve the obstruction while having minimal negative impact on the speech. These
procedures also may be considered in a patient with palatal insufficiency and severe ear
or sinus disease.
Other complications after adenoidectomy include nasopharyngeal stenosis, bleeding,
torticollis, and rarely C-spine subluxation from hyperextension during surgery or
inflammation of the cervical fascia with torticollis postoperatively. Care must especially
be taken to avoid such spinal injury in patients with Down syndrome, who are at risk for
subluxation. Most children do well after adenoidectomy; the most common complaint
from parents is malodorous breath, which may last for 1 to 2 weeks after surgery.
Tonsils
Penicillin continues to be the first-line antibiotic used in acute tonsillitis due to GABHS.
Even when the throat culture is negative for GABHS, antibiotic therapy appears to be
effective in improving symptoms. In chronic tonsillitis and obstructive tonsillar
hyperplasia, a therapeutic trial with an antibiotic effective against -lactamaseproducing
microorganisms or encapsulated anaerobes (such as amoxicillin-clavulanate or
clindamycin) for 3 to 6 weeks may be beneficial and obviate the need for tonsillectomy in
about 15% of children. This approach may be particularly useful in the older child, who
may grow into the large tonsils and adenoids if a small reduction in size is realized. The
role of prophylaxis in recurrent infection is useful, particularly when tonsillectomy
presents undue surgical risk or is unacceptable to the family at a given time.
When enlarged tonsils and/or adenoids cause an acute upper airway obstruction, a
nasopharyngeal airway is the most effective way to achieve immediate relief. Proper
placement is confirmed by direct flexible nasopharyngoscopy or by clinical evaluation.
Patients with infectious mononucleosis are at particular risk for acute airway obstruction.
Systemic corticosteroids and antimicrobial therapy are instituted; however, amoxicillin
should not be used in patients with infectious mononucleosis because of the potential for
severe skin rash. When a PTA coexists with infectious mononucleosis or in a child with a
poor clinical response to medical therapy, immediate tonsillectomy is sometimes needed;
however, most patients get through the acute phase without surgery.
Despite advances in medical therapy, tonsillectomy continues to be the mainstay of
treatment for chronic tonsillar disease (Table 81.6). For elective tonsillectomy, the risks
of postoperative hemorrhage, emesis resulting in dehydration, general malaise, fever,
malodorous breath, and throat pain should be discussed in detail preoperatively with the
parents and older child. Although most postoperative bleeding can be managed without
blood transfusion, it is prudent to discuss this prior to the initial procedure. For Jehovah's
Witnesses, who eschew transfusions for religious reasons, this is especially important.
Some surgeons agree to respect the wishes of the family, while others will obtain a court
order to treat a child in dire need. Comparative morality is beyond the scope of this
discussion, but the family should know the surgeon's or institution's philosophy as a
component of informed consent. Many people incorrectly regard tonsillectomy and
adenoidectomy as a minor procedure because it is performed so commonly. Taking
time in the preoperative period to prepare the family and child will help to decrease
unrealistic postoperative expectations and perhaps complications (Table 81.7).

TABLE 81.6. INDICATIONS FOR
TONSILLECTOMY
a




TABLE 81.7. COMPLICATIONS
ADENOTONSILLAR DISEASE AND
ADENOIDECTOMY AND TONSILLECTOMY



A careful medical history should be taken with specific reference to any bleeding history
in the family. When present, a reasonable screening for coagulopathy should include
bleeding time and partial thromboplastin time (18). Abnormal results or the suspicion of
specific factor deficiency from the family history should prompt a hematology consult.
Hematology can offer guidance in helping manage children with hemoglobinopathies.
The sickle cell patient requires careful management of fluids and blood oxygenation to
avoid inducing vaso-occlusive crisis. Family history for adverse reactions to anesthesia
may reveal the potential for malignant hyperthermia. Children with Down syndrome
should have cervical spine films (extension and flexion) to check for C12 subluxation to
reduce risk of hyperextension injury to the neck. Because of alterations in fluid and
caloric intake in the perioperative period, diabetes mellitus may be much harder to
manage and may require close endocrinologic care. All other chronic medical problems,
such as seizures, asthma, and cardiac abnormalities, also should be thoroughly evaluated
and stabilized before surgery.
Techniques for tonsillectomy vary widely, each with its own advantages; however, the
principles of careful dissection in the subcapsular plane and meticulous hemostasis
underlie all techniques. Variations in technique usually revolve around the method of
dissection (cold knife, hot knife with cautery, ultrasonic scalpel, microscopic bipolar
cautery, KTP laser) and the methods for hemostasis (cautery, chemical, laser, or suture).
Our preferred technique is described elsewhere (19).
The postoperative management in the early phases of recovery most often centers on
protection of the airway until the patient is fully awake. Small amounts of blood or
secretions at the laryngeal inlet can lead to reflex laryngospasm upon extubation. For
children who present little or no increased surgical risk and do not require a longer in-
hospital observation time after tonsillectomy and adenoidectomy, we have implemented
procedures for early discharge. These include intraoperative administration of an
antiemetic, antibiotic, analgesic, and fluid replacement. The use of local analgesia (20) or
intravenous steroids (21) are the individual surgeon's choice. When the child is alert
enough for discharge, he or she can leave the same-day surgery unit without needing to
establish oral intake. Follow-up phone calls are made by same-day surgery nurses that
evening and the following morning. Once the child is home, the family is advised to
allow the child to return to normal activity and diet (22,23) as tolerated. Most children
complete a 10-day course of amoxicillin to help reduce the pain and malodorous breath
often encountered postsurgically.
Same-day tonsillectomy surgery has become very popular in many parts of the country
(24); however, stringent criteria should be applied to ensure that children at greatest risk
during the first 24 hours after surgery are not sent home too early:
1. Those with obstructive sleep apnea or craniofacial syndromes involving the
airway
2. Those experiencing vomiting or hemorrhage
3. Those under 3 years of age
4. Those who live more than 60 minutes from the hospital
5. Those who come from a socioeconomic environment in which inadvertent neglect
may lead to complications
6. Those with any other medical problems, such as Down syndrome, significant
asthma, diabetes, seizures, complex or unstable cardiac disease, that might lead to
complications if not closely managed (25)
The most common complications after tonsillectomy are emesis, dehydration,
hemorrhage, and airway obstruction. Pulmonary edema may occur rarely after the relief
of both acute and chronic airway obstruction. Presentation and management of
complications are presented in Table 81.7.
PERITONSILLAR ABSCESS
Once considered as a complication of tonsillitis, PTA is now thought to be secondary to
infection of a peritonsillar salivary gland (Weber gland) located between the tonsil
capsule and the muscles of the tonsillar fossa (26). Characterized by a severe sore throat,
odynophagia with drooling, muffled voice, and trismus, PTA is most frequently seen in
older children, adolescents, and adults. Physical examination reveals a peritonsillar bulge
with medial and inferior displacement of the tonsil. Often the tonsils themselves appear
normal.
Treatment includes hydration, pain relief, and antibiotics effective against
Staphylococcus aureus and oral anaerobes. Needle aspiration is effective treatment in
75% of children with PTA (27) and is advocated as the first line of therapy unless a past
history of recurrent tonsillitis or prior PTA would suggest that immediate tonsillectomy
would be indicated. Once needle aspiration has been performed successfully, if the
patient can tolerate oral intake, an intravenous dose of clindamycin and a fluid push are
administered in the emergency department. Outpatient follow-up for the first several days
is implemented until recovery is assured. Patients with poor oral intake, systemic toxicity,
impending airway obstruction, severe trismus, or large abscesses are more effectively
managed in an inpatient setting.
LINGUAL TONSILS
The lingual tonsils sit on the posterior aspect of the tongue as it defines the hypopharynx
and vallecula. Infection or inflammation of the lingual tonsils may present with an acute
or chronic sore throat and odynophagia. Extraesophageal reflux is a prime contributor to
chronic lingual tonsillitis. Airway obstruction secondary to lingual tonsillitis with
obstructive hyperplasia also has been reported. The use of a nasopharyngeal airway to
bypass the obstruction (or any other significant acute obstruction from the tonsils and
adenoids) may be used initially with the institution of antimicrobial therapy and possibly
corticosteroids. Surgical excision is rarely necessary; electrocautery and laser lingual
tonsillectomy have been advocated.
UNILATERAL TONSIL HYPERPLASIA
When one tonsil is much larger than the other, most often chronic bacterial infection or
asymmetric placement in the fossa is causative; however, the clinician must suspect
unusual infections or neoplasia as the etiology. Mycobacterium tuberculosis, atypical
mycobacteria, fungal organism, or actinomycosis may all be infectious causes of
unilateral hyperplasia. Neoplastic processes, particularly the lymphomas, also must be
considered.
When removing a tonsil for diagnosis, preoperative consultation with the pathologist is
needed for proper processing of the specimen. The oncologist may want a simultaneous
bone marrow biopsy if a malignancy is strongly suspected. Appropriate culture
techniques also are recommended, and consultation should be sought with laboratory
personnel as required.

HIGHLIGHTS
Tonsillectomy and adenoidectomy are among the most
commonly performed surgical procedures in the United States
today; however, a decline in the role of tonsillectomy and
adenoidectomy despite an increasing population base is due to
advances in medical therapy and more stringent criteria for
surgery (Table 81.5 and Table 81.6).
The adenoids and tonsils, by virtue of their unique anatomic
locations and differential functions, have characteristic clinical
presentations. Therefore, they must be evaluated as two
separate organs and often require separate management (Table
81.1).
Understanding the basic pathophysiology of the diseases of the
tonsils and adenoids will lead the clinician to explore new
avenues of medical management before consideration is given
to adenoidectomy and/or tonsillectomy.
Both the history and physical examination of the tonsils and
adenoids should be performed separately and with attention to
detail. Appropriate use of adjunctive laboratory evaluations is
recommended (Table 81.4).
Tonsillectomy and adenoidectomy are major surgical
procedures. They require the diligence of the physician to be
aware of all the possible complications and treat them with care
and respect. Informed consent must include explanations of the
normal recovery process as well as unexpected complications.
Identification of higher risk patients preoperatively, with
appropriate perioperative and postoperative management, will
increase the safety of these procedures.
Mirror visualization adenoidectomy is the preferred method for
removal to assess the extent of removal, to avoid certain
anatomic areas where scarring may be a problem, and to
provide improved hemostasis.
Several methods of tonsillectomy exist, almost all require
careful dissection in the subcapsular plane and meticulous
hemostasis.
Peritonsillar abscess may be managed by needle aspiration with
inpatient follow-up. Selected patients require immediate
tonsillectomy.
CHAPTER REFERENCES
1. Watanabe T, Fujiyoshi T, Tomonaga K, et al. Adenoids and otitis media with effusion in children.
Adv Otorhinolaryngol 1992;47:290296.
2. Bernstein JM, Faden HF, Dryja DM, et al. Micro-ecology of the nasopharyngeal bacterial flora in
otitis-prone and nonotitis-prone children. Acta Otolaryngol (Stockh) 1993;113:8892.
3. Van Cauwenberge PB, Bellussi L, Maw AR, et al. The adenoid as a key factor in upper airway
infections. Int J Pediatr Otorhinolaryngol 1995;32(suppl):7180.
4. Tankel JW, Cheesman AD. Symptom relief by adenoidectomy and relationship to adenoid and
post nasal airway. J Laryngol Otol 1986;100:637640.
5. Brodsky L, Koch R. Bacteriology and immunology of normal and diseased adenoids in children.
Arch Otolaryngol Head Neck Surg 1993;119:821829.
6. Kuhn JJ, Brook I, Waters CL, et al. Quantitative bacteriology of tonsils removed from children
with tonsillitis hypertrophy and recurrent tonsillitis with and without hypertrophy. Ann Otol
Rhinol Laryngol Suppl 1995;104:646652.
7. Fearon M, Bannatyne RM, Fearon BW, et al. Differential bacteriology in adenoid disease. J
Otolaryngol 1992;21:434436.
8. Brook I, Foote P. Microbiology of the tonsils and adenoids. Arch Otolaryngol 1989;115:528530.
9. Finegold SM. Role of anaerobic bacteria in infections of the tonsils and adenoids. Ann Otol Rhinol
Laryngol Suppl 1991;154:3033.
10. Scadding GK. Immunology of the tonsil: a review. J R Soc Med 1990;83:104107.
11. Vanderberg SJ, Heatley DG. Efficacy of adenoidectomy in relieving symptoms of chronic
sinusitis in children. Arch Otolaryngol Head Neck Surg 1997;123:675678.
12. Barbero GJ. Gastroesophageal reflux and upper airway disease. Otolaryngol Clin North Am
1996;29:1:2738.
13. Paradise J, Bluestone C, Bachman R, et al. Efficacy of tonsillectomy for recurrent throat infection
in severely affected children. N Engl J Med 1984;310:674683.
14. Mui S, Rasgan BM, et al. Efficacy of tonsillectomy for recurrent throat infection in adults.
Laryngoscope 1998;108:13251328.
15. Gates G, Cooper J, Avery C, et al. Chronic secretory otitis media: effects of surgical management.
Ann Otol Rhinol Laryngol Suppl 1989;98:231.
16. Marcus CL, Omlin KJ, et al. Normal polysomnographic values for children and adolescents. Am
Rev Respir Dis 1992;146:12351239.
17. Anonymous. Standards and indications for cardiopulmonary sleep studies in children. Am J Respir
Crit Care Med 1996;153:866878.
18. Howells RC II, Wax MK, Ramadan, HH. Value of preoperative prothrombin time/partial
thromboplastin Time as a predictor of post-operative hemorrhage in pediatric patients undergoing
tonsillectomy. Otolaryngol Head Neck Surg 1997;117:628632.
19. Andrea M. Microsurgical bipolar cautery tonsillectomy. Laryngoscope 1993;103:11771178.
20. Johansen M, Harbo G, Illum P. Preincisional infiltration with bupivacaine in tonsillectomy. Arch
Otolaryngol Head Neck Surg 1996;122:261263.
21. April MM, Callan ND, Nowak DM, et al. The effect of intravenous dexamethasone in pediatric
adenotonsillectomy. Arch Otolaryngol Head Neck Surg 1996;122:117120.
22. Hall MD, Brodsky L. The effect of post-operative diet on recovery in the first twelve hours after
tonsillectomy and adenoidectomy. Int J Pediatr Otorhinolaryngol 1995;31:215220.
23. Brodsky L, Radomski K, Gendler J. The effect of post-operative instructions on recovery after
tonsillectomy and adenoidectomy. Int J Pediatr Otorhinolaryngol 1993;25:13, 133140.
24. Gabalski EC, Mattucci KF, Setzen M, et al. Ambulatory tonsillectomy and adenoidectomy.
Laryngoscope 1996;106:7780.
25. Gerber ME, O'Connor DM, Adler E, et al. Selected risk factors in pediatric adenotonsillectomy.
Arch Otolaryngol Head Neck Surg 1996;122:811814.
26. Passy V. Pathogenesis of peritonsillar abscess. Laryngoscope 1994;104:185190.
27. Weinberg E, Brodsky L, Stanievich J, et al. Needle aspiration of peritonsillar abscess in children.
Arch Otolaryngol Head Neck Surg 1993;119:169172.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

82 CONTROVERSIES IN TONSILLECTOMY, ADENOIDECTOMY, AND TYMPANOSTOMY TUBES
Head & Neck SurgeryOtolaryngology
82




CONTROVERSIES IN TONSILLECTOMY,
ADENOIDECTOMY, AND TYMPANOSTOMY
TUBES
CHARLES D. BLUESTONE

C.D. Bluestone: Department of Pediatric Otolaryngology, Children's Hospital of Pittsburgh, Pittsburgh,
Pennsylvania.


The Problem
Certain Indications for Tonsillectomy and Adenoidectomy
Elective Indications for Tonsillectomy
Recurrent Acute Tonsillitis
Chronic Tonsillitis and Hypertrophy
Peritonsillar Abscess
Elective Indications for Adenoidectomy
Obstructive Adenoids and Adenoiditis
Recurrent Acute and Chronic Sinusitis
Otitis Media
Chapter References
Despite the current availability of randomized clinical trials that have assessed the
efficacy of the most common presumed indications for tonsillectomy, adenoidectomy,
and myringotomy and tympanostomy tube placement, controversy still exists not only
among physicians, but also among patients, their families, and health care administrators
and payers. Many clinicians still are concerned that the expected benefits of these
procedures do not outweigh their potential risks and known costs. This chapter reviews
the results of these trials, relates their findings to clinical decision making, and discusses
other potential indications for these procedures that have not been subjected to rigorously
controlled randomized clinical trials and subsequently reported.
The current state of evidence-based otitis media has recently been edited and compiled by
Rosenfeld and Bluestone, which includes the current state of knowledge related to
surgical indications (1). Also, Chapter 86 and Chapter 92 in this text provide further
information and other opinions on this subject.
In a randomized clinical trial reported over 15 years ago, we found that tonsillectomy can
benefit children who suffer from frequently recurrent throat infection, but in a more
recent trial with patients who had fewer episodes (i.e., were less severely affected), we
found the operation was no more effective than withholding the tonsillectomy in
preventing moderate to severe throat infections. With these two trials in mind, we can
now predict that tonsillectomy, in children who meet the frequency, severity, and
characteristics of episodes that met our criteria in our first trial, will be more effective
than not performing this operation. Related to the efficacy of tonsil and adenoid surgery
for otitis media, we conducted a randomized trial that showed that adenoidectomy can
reduce the frequency of recurrent acute otitis media in children who had had
tympanostomy tubes previously inserted, but continued to experience recurrent attacks
after the tubes had extruded. We reported a trial that revealed a lack of efficacy of
adenoidectomy, with or without the addition of tonsillectomy, for this indication in
children who had never received tympanostomy tubes in the past (i.e., were less severely
affected). At least three relatively large-scale randomized clinical trials have
demonstrated that adenoidectomy is efficacious in children who had chronic otitis media
with effusion, whether or not tympanostomy tubes had been previously placed.
Tympanostomy tube placement, without the addition of adenoidectomy, has been shown
to be effective in clinical trials, in the management of both chronic otitis media with
effusion and frequently recurring acute otitis media. Myringotomy alone for treatment of
chronic otitis media was found to be no more effective than no surgery and is not
recommended for this indication, but remains an important surgical option when acute
otitis media is severe, unresponsive to antimicrobial treatment, or when a suppurative
complication develops.
We must improve the process of selecting candidates for surgery when the goal is to
prevent recurrent throat infection or otitis media by attempting to identify those children
who are at highest risk for recurrence, because they could benefit from earlier surgical
intervention. Also, rigorously controlled randomized clinical trials should be performed
to evaluate the effectiveness of tonsillectomy and adenoidectomy when upper airway
obstruction is present. These surgical procedures are known to be beneficial when
obstructive sleep apnea (OSA) or cor pulmonale are complications of upper airway
obstruction due to the tonsils and adenoids, but for less severely affected infants and
children, the indications for surgery are less distinct. Also, randomized clinical trials
should be conducted to test the efficacy of adenoidectomy in patients who suffer from
recurrent/chronic paranasal sinusitis. Likewise, clinical trials are needed to determine the
efficacy of tonsillectomy when chronic tonsillitis is diagnosed, and to identify the
indicationsand timingof tonsillectomy when a peritonsillar abscess develops.
The decision-making process for or against surgical intervention should continue to
improve as information derived from other clinical trials is reported in the future; this in
turn should enhance the quality of health care for patients with recurrent/chronic throat,
ear, and sinus infections, as well as upper airway obstruction due to the tonsils and
adenoids. Controversy will remain until future trials are completed and reported for
indications that are not yet evidence based; until then, treatment should be individualized
for each patient. When the indications are evidence based, however, the decision for
performing tonsillectomy, adenoidectomy, and tympanostomy tube placement can be
supported by the results of randomized clinical trials, and should not be controversial.
THE PROBLEM
Myringotomy and tympanostomy tube placement is the most common operation
performed in children in the United States (2). The most common major surgical
procedures performed in children continue to be tonsillectomy and adenoidectomy. In
1996, 1 of every 110 children had tympanostomy tubes inserted, which was
approximately twice the rate of tonsillectomy. More than 1 million tonsillectomies and
adenoidectomies were performed in the United States in the early 1970s, but only about
250,000 procedures have been performed more recently, roughly an 80% decrease. The
dramatic decrease in frequency during this period is probably due to many factors. But,
one factor during the past 30 years was the concern by the health care community of a
lack of convincing evidence derived from randomized clinical trials that these operations
were effective in preventing recurrent throat infections and otitis media, the most
common conditions for which the procedures were performed.
Otitis media is one of the most common diseases throughout the world and affects all
ages, both sexes, and all races. It is the most common diagnosis made by physicians in
the United States, and a dramatic increase in this diagnosis has been seen in infants and
young children over the past two decades (3). Although relatively infrequent in adults,
these infections primarily affect infants and young children and, to a lesser degree, older
children and teenagers. It is estimated that approximately 20,000 adults have
tympanostomy tubes inserted annually in the United States. Nevertheless, otitis media is
highly prevalent in children, especially in infants. In a prospective study, Teele and co-
workers (4) studied 498 children from birth to 7 years of age and found that the mean
number of episodes of otitis media in the first year of life was 1.2; 17% of children had
three or more episodes (4). For the next 6 years of life, about 75% had at least one
episode per year. In a more recent prospective study of both white and black infants
followed from soon after birth to their second birthday, Casselbrant and colleagues (5)
found that almost 90% had at least one episode of otitis media; in contrast to earlier
studies, the rates were similar in whites and blacks.
Why is there such a high incidence of otitis media in infants and young children, and why
are these rates increasing? One of the most important risk factors has recently been
confirmed in a prospective study of twin and triplet infants reported from Pittsburgh in
which the estimate of heritability of otitis media was 73% (6). Environmental factors, not
genetics, are related to the ever-increasing rate seen in the United States. In a study by
Wald and colleagues (7) of children in Pittsburgh, 21% of children who attended group
day-care centers had tympanostomy tubes in place compared with 3% of children who
stayed at home (7). The researchers could not conclude that this difference was due to
variations in health care management. Most likely, the incidence of otitis media is
increasing because of the increasing use of group day care for these age groups. A similar
phenomenon was reported by Paradise and associates (8), who recently reported an
increase in the rate of otitis media related to the number of offspring in the family. The
reasons for the increased rate of otitis media in infants and young children can be better
understood by reviewing what we know about the etiology and pathogenesis of otitis
media, which is multifactorial. An episode of otitis media is usually preceded by an upper
respiratory tract viral infection, which then progresses into a secondary bacterial middle-
ear infection. Bacteria enter the middle ear through a structurally and functionally
immature eustachian tube; the eustachian tube in infants and young children is shorter
and has a less efficient opening mechanism than in older children and adults. Because the
immunologic status of infants and young children is also immature compared with that of
older children and adults, they are more susceptible to upper respiratory tract viral
infections and thus otitis media. Also, many studies have shown that group day-care
centers are associated with an increased incidence of ear disease and that breast-feeding
confers a lower incidence of ear disease (7,8,9 and 10). Therefore, the incidence of otitis
media probably will increase with the increasing availability of day-care centers in the
United States.
The annual financial impact of otitis media on the health care system in the United States
has been estimated to be about $5 billion (11), but when the direct and indirect costs of
each episode of otitis media are estimated to be approximately $1,300, the total costs may
be as high as $18 billion per year (12). Approximately 120 million prescriptions are
written for oral antimicrobial agents each year in the United States, and of these, more
than 25% are for treatment of otitis media, according to market surveys. Investigators for
the U.S. Food and Drug Administration found that of the 45 million courses of antibiotics
prescribed for children under 10 years of age in 1986, 42% were for otitis media (13).
Estimates of the annual number of myringotomy and tympanostomy tube operations in
the United States range from about 400,000 to 1 million (14,15). This number is probably
even greater today with the increasing incidence of recurrent and chronic middle-ear
infections in infants and young children and the recent recommendations to only use
antimicrobial prophylaxis in selected cases, due to the ever-increasing increase in
multidrug-resistant bacterial pathogens causing otitis media (16).
CERTAIN INDICATIONS FOR TONSILLECTOMY AND
ADENOIDECTOMY
Despite the lack of randomized clinical trials, due to ethical considerations, we have
become increasingly aware during the past three decades that there are certain (as
opposed to elective) indications for these procedures (17). Infants and children who have
obstructive tonsils or adenoids that result in obstructive sleep apnea should have their
tonsils or adenoids or both removed (18,19,20,21 and 22). Obstructive sleep apnea has
been classified as being part of the overall pathologic condition termed sleep-related
breathing disorders, which also includes the upper airway resistance syndrome and the
obstructive hypopnea syndrome (23). Obstructive sleep apnea in children has been
associated with not only cor pulmonale and right-sided heart failure, systemic
hypertension, failure to thrive, and enuresis, but also neurocognitive and behavioral
abnormalities (24). A recent study showed that obstructive sleep apnea syndrome
adversely affects insulin-like growth factor-1 (IGF-1) in children, and that both IGF-1
and weight gain increased following adenotonsillectomy (25). The term obstructive
tonsils and adenoids is preferred, because the degree of obstruction relates to several
factors, such as the size of the tonsils and adenoids compared with the pharyngeal space
and body position. The obstruction is usually most pronounced when the child is in the
supine position and during sleep, when the pharyngeal muscles and jaw are relaxed.
Hypertrophy of the tonsils and adenoids may or may not be involved in the etiology and
pathogenesis of the obstruction, because even small tonsils or adenoids can cause severe
obstruction when the pharynx is shallow (i.e., a small anteroposterior dimension).
Obstructive tonsils also should be removed if they are unresponsive to antimicrobial
therapy and cause failure to thrive or progressive weight loss as a result of marked
swallowing impairment. For the rare child who has a suspected malignancy of the tonsil,
excisional biopsy (i.e., tonsillectomy) is the preferred procedure. An occasional child has
persistent/recurrent tonsillar hemorrhage, either associated with acute pharyngotonsillitis
or due to tonsillar hypertrophy; when this condition is severe, tonsillectomy is indicated.
The following are methods to assess upper airway obstruction resulting from obstructive
tonsils or adenoids:
1. History, such as snoring, sleep pauses/apnea, mouth breathing, and daytime
somnolence (26,27). However, snoring alone, in the absence of other signs and
symptoms, may not be indicative of obstructive adenoids and tonsils (28).
2. Physical examination, which may reveal a lack of lip seal, mouth breathing,
hyponasality, and distortion of speech (such as hot-potato voice). In extreme
cases, the examination may reveal evidence of congestive heart failure.
Examining the intranasal cavity or postnasal space by direct or indirect
rhinoscopy may reveal nasal obstruction secondary to obstructive adenoids.
Flexible fiberoptic endoscopic examination may help to evaluate the degree of
nasal obstruction secondary to the adenoids.
3. Radiographs may be desirable in the child who is difficult to examine. A soft-
tissue lateral radiograph of the head and neck can help to determine the degree of
nasal obstruction attributable to obstructive adenoids.
4. A formal sleep study may be indicated if a child has a history of sleep
disturbances at night and the parents are uncertain whether the child has sleep
pauses or true sleep apnea (29,30,31 and 32); in many infants and children,
however, such a study is not feasible. Alternatively, the parents can use a cassette
player to tape the child's sleep for about 5 to 10 minutes for two consecutive
nights (33). The clinician and parents then assess the tape to determine whether
the child does snore while sleeping, and, if so, whether there are sleep pauses or
apneic episodes.
Potential factors related to the development of cardiorespiratory complications in patients
with respiratory obstruction due to tonsils or adenoids may include one or more of the
following: (a) susceptibility of the pulmonary vasculature; (b) craniofacial malformation,
such as in Down syndrome (34,35); (c) obesity (e.g., Pickwickian syndrome); (d)
preexisting congenital heart disease; (e) abnormal pharyngeal musculature; and (f)
concurrent upper respiratory tract infection.
When a diagnosis of severe airway obstruction is confirmed and the child has either sleep
apnea or evidence of alveolar hypoventilation, with or without cor pulmonale,
tonsillectomy and adenoidectomy are usually indicated. Sometimes the adenoids totally
obstruct the nasopharyngeal airway, but the tonsils may be relatively small; conversely,
the tonsils may obstruct the oropharyngeal airway in association with small or absent
adenoids (36). In such cases a tonsillectomy or adenoidectomy may be performed, but in
most children both the tonsils and adenoids are involved in the process. When in doubt,
both the tonsils and adenoids should be removed (31). Outpatient adenotonsillectomy
appears to be safe for many children (37), but patients who have obstructive sleep apnea
(especially infants and young children) should be monitored for possible postoperative
respiratory compromise in the hospital the night of the surgery (38). Even children under
36 months of age who are candidates for adenotonsillectomy and do not have obstructive
sleep apnea should be strongly considered for a planned overnight stay not just for
reasons of safety, but this practice has been shown to be more cost effective in this age
group (39). Even though a great deal of information is available today regarding the
pathophysiology of upper respiratory obstruction secondary to obstructive tonsils and
adenoids, more research is needed, especially in children who lack signs and symptoms
of severe airway obstruction.
ELECTIVE INDICATIONS FOR TONSILLECTOMY
The preceding indications are considered certain indications for tonsillectomy and
adenoidectomy, but most of these procedures are recommended on an elective basis. For
these children, we must review the results of the randomized clinical trials conducted and
reported in the past decade.
Elective tonsillectomy is most commonly indicated for:
1. Recurrent acute tonsillitis
2. Chronic tonsillitis
3. Obstructive tonsils
4. Peritonsillar abscess
Of these four, a randomized clinical trial has been conducted and reported for only one
indication, frequently recurrent acute pharyngotonsillitis.
Recurrent Acute Tonsillitis
In 1984, Paradise and colleagues (40) reported the results of a randomized clinical trial
involving 187 children severely affected with recurrent pharyngotonsillitis (Table 82.1).
Subjects were eligible if their episodes met the following criteria:

TABLE 82.1. EFFICACY OF TONSILLECTOMY
FOR PREVENTION OF RECURRENT THROAT
INFECTION



1. Frequency of occurrence. Seven or more episodes in the preceding year, five or
more in each of 2 preceding years, or three or more in each of 3 preceding years.
2. Clinical features. Each episode had one or more of the following characteristics:
oral temperature of at least 38.3C, cervical lymphadenopathy [enlarged (>2 cm)
or tender cervical nodes], tonsillar exudate, or positive throat culture for group A
-hemolytic streptococcus (GABHS). Not all episodes had to have a positive
streptococcal throat culture to meet eligibility criteria.
3. Antimicrobial treatment for proven or suspected streptococcal episodes.
4. Documentation of the episodes. Children with undocumented episodes were
followed to determine whether they truly had tonsillitis. As reported by Paradise
and co-workers (41), many children failed to have the frequency or severity
described by their parents.
After the first and second years, in subjects randomly assigned to either tonsillectomy or
nonsurgical control, tonsillectomy was effective. Third-year outcomes were also better in
the surgical group, but the differences were not statistically significant. Ninety-six
subjects were not randomized and were assigned tonsillectomy or no surgery according to
their parents' decision. The outcomes for these children were similar to those of subjects
in the randomized trial. Because many subjects in the randomized control group and the
randomized no-surgery groups also improved to some degree, we recommended that the
choice of nonsurgical or surgical treatment for such children be individualized. The
results did show, however, that tonsillectomy significantly reduced the number of
episodes of throat infection over the follow-up period, including episodes of throat
infection due to GABHS. We concluded that elective tonsillectomy for stringent criteria
is a reasonable alternative to medical treatment for children with frequently recurrent
throat infections.
For children less severely affected (i.e., four or five episodes of throat infection in 1
year), a clinical trial was completed by Paradise and co-workers (42). The results of this
trial showed that tonsillectomy reduced the overall number of sore throats, but in contrast
to the first clinical trial in which the frequency of the throat infections were greater at
entry into the trial, there was no statistical significance in the rates of moderate to severe
throat infections between the tonsillectomy group and the control group in the second
trial. We concluded from that trial that the entry criteria used in the first study are more
appropriate for clinical decision making today; however, the clinician must individualize
each child's history and signs and symptoms. In addition to the frequency of throat
infections, the severity and duration of each episode must be assessed. For example, a
child who does not strictly meet the criteria established in the first trial and had had only
four or five episodes in the previous year, but one or two of these attacks required
hospitalization, should be considered a candidate for tonsillectomy.
Microbiology Related to Treatment
Related to indications for tonsillectomy for recurrent tonsillitis, there has been increasing
interest in the microbiology of this infection and whether other bacteria found in the core
of the tonsils are involved in the infection in addition to those thought to be pathogenic
(such as GABHS, non-GABHS, Corynebacterium diphtheriae, Corynebacterium
hemolyticum, Neisseria gonorrhoeae, and Chlamydia trachomatis). Kielmovitch and
colleagues (43) found polymicrobial organisms in the core of the tonsils of children with
recurrent tonsillitis and in those with obstructive tonsils. There was a high prevalence of
Streptococcus pyogenes in both groups as well as -lactamaseproducing aerobic and
anaerobic organisms. From this study, we, like others in the past, speculated that the high
rate of S. pyogenes in the core of tonsils obtained from these children could have resulted
in a persistent streptococcal infection due to the passive pathogenicity of the other
bacteria found in the core of the tonsils that were -lactamase producing (44). These
other bacteria may not be pathogenic, but because they can produce free -lactamase, the
therapeutic activity of penicillin may be impaired when S. pyogenes is the causative
organism. Another hypothesis is that bacterial interference is also involved in the possible
reason for penicillin failures in treating streptococcal pharyngitis. Brook and Gober (45)
evaluated 52 children with acute GABHS pharyngitis and showed that children who
failed to respond to penicillin therapy harbored more -lactamaseproducing bacteria and
less GABHS-inhibiting -hemolytic streptococcus per child than did children who
responded to therapy. More recently, these same investigators suggest that interfering
organisms, such as nonhemolytic streptococci and anaerobic bacteria, may play a role in
preventing GABHS pharyngitis (46).
With these hypotheses in mind, some have called for reevaluation of penicillin as the
drug of choice, especially for recurrent tonsillopharyngitis (47). But in a recent report,
Gerber and associates (48) reaffirmed the use of penicillin V for GABHS pharyngitis, as
opposed to initial treatment with a cephalosporin, and reported that neither -lactamase
nor bacteriocin produced by normal pharyngeal flora are related to bacteriologic
treatment failures in GABHS pharyngitis.
In such cases, it is postulated that a -lactamase stable antimicrobial agent or one with a
-lactamase inhibitor will be more effective in eradicating the streptococcal infection.
There is now evidence that such agents are more effective than penicillin (49); however,
for routine treatment of uncomplicated streptococcal throat infection, penicillin is still
recommended by most authorities as the drug of choice. A study by Brook and Hirokawa
(50) compared penicillin, erythromycin, and clindamycin in 45 patients with a history of
recurrent (three per year for 2 years) GABHS throat infections. The mean age of subjects
was 15 years (range, 8 to 24 years). All the patients were carriers for GABHS when
entering the study, but only one of the 15 subjects on clindamycin had a positive culture
10 days after completing the treatment compared with 13 of 15 in the penicillin group. Of
the 15 in the erythromycin group, 9 had a persistent positive culture. After a 1-year
follow-up, recurrent tonsillitis occurred less frequently in the clindamycin group than in
the penicillin group; of the 15 on penicillin, 12 had one or more episodes (6 were positive
for streptococcus) compared with only 1 of the 15 on clindamycin. Even though this
study is inconclusive, the results are provocative in light of the possible role played by -
lactamaseproducing bacteria isolated from the tonsillar core of patients who have had
recurrent tonsillitis. With this information in mind, the clinician should consider an
alternative to penicillin (e.g., clindamycin, amoxicillin-clavulanate, or one of the newer
cephalosporins) when a child has had recurrent episodes of streptococcal
pharyngotonsillitis in an attempt to treat the underlying infection effectively. Although
some would advocate a course of antimicrobial therapy for longer than the traditional 10
days, there is no evidence today that a longer course is more effective than the currently
recommended duration.
Clinical Decision Making
In accordance with the study by Paradise and co-workers (40), when the clinician is
confronted with a patient who has recurrent acute tonsillitis, the frequency, severity, and
duration of the episodes should be assessed, along with the child's disability, such as days
lost from school. Features that should be present include tonsillar exudate, fever, and
cervical lymphadenopathy; the clinician should determine whether -hemolytic
streptococcus can be isolated from throat cultures and whether the child has failed
appropriate, adequate antimicrobial therapy. One or more episodes must be documented
before making a decision for surgery. Although the frequency of throat infections in
children in the Pittsburgh study showed that tonsillectomy was more effective than no
tonsillectomy, each child's experience with this disease should be assessed, and the
decision for or against surgery should be individualized.
Chronic Tonsillitis and Hypertrophy
As stated above, no randomized clinical trials have addressed the question of the efficacy
and safety of tonsillectomy for chronic tonsillitis. This is a major reason why there is
currently no consensus on the definition of chronic tonsillitis. Clinical trials have
probably not been reported to date for this reason. Because the patient frequently
complains of chronic sore throat, but the tonsils are neither obstructing nor has recurrent
acute throat infection been present, outcome measures of such a trial would have to rely
on the patient's subjective symptoms. When the patient does have chronic sore throat in
association with recurrent acute throat infection that meet the criteria for tonsillectomy
cited above, the decision is relatively straightforward. When the tonsils obstruct the
pharynx, resulting in symptomatic chronic airway obstruction, surgery is a more
reasonable option. In the absence of associated obstruction or recurrent acute throat
infection, or both, the clinician must assess the duration and severity of the illness and the
associated disability individually for each case.
For patients with obstructive tonsils, in the absence of obstructive sleep apnea or cor
pulmonale, surgery is warranted, depending on the duration and severity of the illness.
Features that should be present include snoring and hot-potato voice, which may be
documented on audiotape by the parents at night. A course of an antimicrobial agent
might be beneficial in an attempt to reduce the size of the tonsils and to determine
whether subclinical infection exists.
In the study by Kielmovitch and colleagues, S. pyogenes was found in about one fourth of
patients who had obstructive tonsils and who had been previously untreated (43). Beta-
lactamaseproducing organisms in the core of such tonsils might be involved in the
pathologic process. Indeed, a randomized clinical trial was conducted by Sclafani and co-
workers (51) that evaluated the efficacy of a 30-day course of amoxicillin-clavulanate,
compared with its placebo, in children with chronic hypertrophy of the tonsils (and
adenoids), and reported short-term, but not long-term, success over a 2-year period. At
the end of the trial there was still a statistically significant difference favoring the
antibiotic-treated children compared with those who only received placebo, but most
children in the antibiotic group eventually had an adenotonsillectomy. Even though this
study should be replicated, it provides some evidence that a trial of an antimicrobial agent
may be beneficial in some children, prior to recommending surgical intervention,
especially in infants and very young children, when the operation has some increased
risk; the clinician may be able to delay the surgery until the child grows older, if the
antibiotic treatment is successful. Even though some clinicians advocate CO
2
laser partial
tonsillectomy of hypertrophied tonsils, citing reduction in morbidity and complications,
such as postoperative bleeding, this technique has not gained widespread usage; large-
scale clinical trials comparing this method with the standard tonsillectomy are needed.
Peritonsillar Abscess
Peritonsillar abscess as an indication for tonsillectomy also has not been evaluated by a
prospective randomized clinical trial and reported. At either end of the spectrum,
however, the decision may be straightforward. For example, a teenager who has had no
previous throat infections, has a peritonsillar abscess, and is cooperative enough to allow
incision and drainage or needle aspiration (52) of the abscess probably can be treated
successfully on an outpatient basis with the aid of topical and local anesthetic agents.
Such a patient may be monitored to determine whether there will be a recurrence because
the recurrence rates in such patients are relatively low. Some advocate interval
tonsillectomy, however. On the other hand, in a young child who has had frequently
recurrent acute tonsillitis during the previous 1 or 2 years and then develops a
peritonsillar abscess, incision and drainage using topical/local anesthesia usually are not
feasible. The procedure should be performed in the operating room, and at that time a
tonsillectomy also can be performed.
Between these two extremes, physicians must use their best clinical judgment until
further studies addressing the risks and benefits of tonsillectomy for peritonsillar abscess,
either at the time of the acute infection or at a later date, are conducted and reported. A
recent report by Scott and colleagues (53) recommended intraoral ultrasonography to
distinguish between peritonsillar abscess and cellulitis. An alternative, but more costly,
method is computed tomography (CT), but the most cost-effective for clinical diagnosis
is the history and physical examination, although not as reliable as ultrasonography or
CT. Clinical trials should use an objective method of diagnosis, such as ultrasonography
or CT.
ELECTIVE INDICATIONS FOR ADENOIDECTOMY
Adenoidectomy is commonly recommended for four conditions:
1. Obstructive adenoids
2. Recurrent/chronic adenoiditis
3. Recurrent/chronic sinusitis
4. Recurrent acute otitis media and recurrent/chronic otitis media with effusion
Of these indications, only the fourth has been evaluated in randomized clinical trials and
reported, but some information is now available on the other three indications.
Obstructive Adenoids and Adenoiditis
At the Children's Hospital of Pittsburgh, Paradise (54) conducted a randomized clinical
trial in patients with obstructive adenoids. For the child with moderate to severe nasal
obstruction secondary to obstructive adenoids, this trial showed that removing the
adenoids results in less morbidity, such as mouth breathing, snoring, and hyponasality. In
the absence of obstructive sleep apnea syndrome caused by obstruction (i.e.,
hypertrophied adenoids), however, the benefit of the operation remains uncertain (54).
The question then becomes a quality-of-life issue; for instance, improving the nasal
airway has been shown to improve olfaction and may help to prevent or reverse
abnormalities of dentofacial morphology (55,56). In addition, a child with nasal
obstruction has hyponasal speech; after the operation, more normal speech should result
(57). Some clinicians (and parents) think growth and development improve after the
relief of complete nasal obstruction in children with obstructive adenoids. Until the
Pittsburgh study is fully evaluated and reported, the clinician assessing a child with
moderate to severe nasal obstruction resulting in lack of lip seal, hyponasality, and
nocturnal snoring should determine the duration and severity of the obstruction and
decide whether the child truly does have respiratory obstruction at night. An audiotape
recording can help document this finding. A lateral soft-tissue radiograph of the head and
neck may help document the adenoid size.
Because little information is available on the epidemiology, natural history, and etiology
of adenoiditis, it is possible that a child with obstructive adenoids may have chronic
adenoiditis and that a course of antimicrobial therapy may help reduce the degree of nasal
obstruction. The clinical trial (cited above) by Sclafani and colleagues (51) does provide
some evidence that an antimicrobial agent, such as amoxicillin-clavulanate, may be
effective in reducing the size of the adenoids (and tonsils), albeit for the short term.
Recently, intranasal administration of aqueous beclomethasone was advocated to reduce
the size of adenoid hypertrophy and nasal airway obstruction, but this treatment is not
widely used and must await the reporting of a confirmatory clinical trial before it can be
currently recommended (58). Also, a trial of systemic corticosteroids was reported to be
ineffective in reducing the size of hypertrophied adenoids (59). Upper respiratory allergy
also may cause obstructive adenoids; if the child has a history or signs and symptoms of
upper respiratory allergy, it may be worthwhile to investigate this possibility. In the
clinical trial recently conducted in Pittsburgh, however, adenoidectomy was effective in
children with and without documented evidence of allergy. Thus, if allergic children have
obstructive adenoids that are unresponsive to a course of an antimicrobial agent, the child
will most likely benefit from an adenoidectomy even if management of the allergy, such
as immunotherapy, has not been completed.
Recurrent Acute and Chronic Sinusitis
For patients who have frequently recurrent acute sinusitis or chronic sinusitis or both
conditions, the benefit of adenoidectomy remains uncertain. No prospective randomized
clinical trials have demonstrated that adenoidectomy is effective in reducing the
morbidity of sinusitis in children. Four studies have shown efficacy, however, and make a
reasonable case for adenoidectomy in the treatment of chronic sinusitis in children
(60,61,62,63 and 64). No convincing evidence exists that adenoidectomy is effective in
the prevention of recurrent acute sinusitis. Nevertheless, if the child has moderate to
severe nasal obstruction secondary to adenoid obstruction, the operation probably should
be considered to improve the nasal airway. Again, the duration and severity of the
obstruction should be assessed, as should the clinical and radiographic (imaging)
findings. The assessment of the size of the adenoids when the child is not acutely ill may
be misleading. The adenoids most likely increase in size during an acute upper
respiratory tract infection, which may result in sufficient postnasal obstruction to impair
adequate nasal drainage and stasis of nasal secretions, which then results in sinusitis.
Thus, a course of antimicrobial therapy may be indicated because adenoiditis may be
causing the obstruction. Investigation should be undertaken to determine whether upper
respiratory allergy is present; if so, medical treatment, such as systemic antihistamines,
immunotherapy, allergy control, or topical nasal therapy, may help, despite the current
lack of evidence of efficacy.
Clinical trials to determine the possible efficacy of adenoidectomy for sinusitis are
urgently needed. Even though these studies are not available, adenoidectomy should still
be considered, on an individualized basis, for chronic sinusitis, because the operation
appears to be beneficial for this indication based on the few studies that have been
conducted. The procedure also may help prevent recurrent acute sinusitis, despite the lack
of convincing evidence of efficacy.
Otitis Media
I have provided my opinions above on the current indications for tonsillectomy and
adenoidectomy. Some are based on evidence, but most are my recommendations made
from existing information and from my own experience; thus, they are subject to
controversy. However, we are now able to use evidence-based outcomes from many
randomized clinical trials that assessed the efficacy of surgery for management of otitis
media, which should be less controversial. The medical and surgical management of otitis
media, and its complications and sequelae, has been described extensively by Bluestone
and Klein (65), and the surgical indications for acute otitis media and otitis media with
effusion, which are evidence based, have been reported by Bluestone and Lee (66). The
following indications for surgery for otitis media are presented as the clinician would
face a patient, that is, surgical options for prevention of recurrent acute otitis media and
for management of chronic otitis media with effusion.
Recurrent Acute Otitis Media
What evidence is there that myringotomy and tympanostomy tube insertion is effective in
preventing recurrent acute otitis media in infants and young children? Randomized
clinical trials conducted by Gebhart (67) and Gonzales and colleagues (68) showed
tympanostomy tube insertion to be more effective than no surgery in otitis-prone infants,
but both of these trials had problems in design (e.g., subjects with and without middle-ear
effusion were entered) and neither was long term. In an effort to conduct a more rigorous
trial that was long term and to compare tympanostomy tube insertion to one of its popular
alternatives, antimicrobial prophylaxis, Casselbrant and co-workers (69) entered 263
infants, who had three or more episodes of acute otitis media in 6 months, or four or more
attacks in 12 months, with at least one episode being present during the preceding 6
months. None had an apparent middle-ear effusion at entry and all were followed at
monthly intervals for 2 years. At entry, the subjects were randomized into one of three
groups: amoxicillin prophylaxis (20 mg/kg body weight per day) for 2 years, its placebo
for 2 years, or myringotomy and tympanostomy tube placement. Two years was chosen
to determine the limit of the possible efficacy of the antibiotic prophylaxis and outcome
in the tympanostomy tube group after the tubes spontaneously extruded. The trial
demonstrated that both antibiotic prophylaxis and tympanostomy tubes reduced the
overall frequency, duration, and severity of otitis media in 263 infants compared with
placebo over the 2-year period, but otorrhea did occur in the tympanostomy tube group,
and some of the subjects in the prophylaxis group developed an adverse reaction to the
agent (e.g., drug rash, vaginitis) (Table 82.2). It is important to note that amoxicillin
prophylaxis in this trial was effective, compared with its placebo, for about 1 year;
evidently, the children in the placebo group were growing out of the problem after a
year. Thus, the recommendation that if prophylaxis is to be initiated, it should be for
approximately 1 year. Also, the tympanostomy tubes used in this trial remained in place
for 12 to 18 months. It appears that most infants who meet the criteria used in this trial
will require a method of prevention for at least 1 year.

TABLE 82.2. OUTCOME OF A RANDOMIZED 2-
YEAR CLINICAL TRIAL OF AMOXICILLIN
PROPHYLAXIS AND OF TYMPANOSTOMY
TUBE INSERTION VERSUS PLACEBO FOR
PREVENTION OF RECURRENT ACUTE OTITIS
MEDIA IN 264 PITTSBURGH CHILDREN 735
MONTHS OF AGE



With the benefit of this trial, how should the clinician make a decision between
antimicrobial prophylaxis and tympanostomy tube insertion for prevention of frequently
recurrent episodes of acute otitis media today? Other clinical trials also have shown that
prophylactic antimicrobial agents are effective for preventing recurrent acute otitis media
in this age group (70,71), and a metaanalysis confirmed the beneficial effect of antibiotic
prophylaxis (72). Nevertheless, there is growing evidence today, from in vitro and
clinical studies, that long-term, low-dose antimicrobial prophylaxis is associated with the
ever-increasing rise in multidrug-resistant Streptococcus pneumoniae (16,73,74).
One option would then be, if the episodes are relatively infrequent, to recommend using
no antimicrobial prophylaxis or tympanostomy tube placement, because the child will
most likely improve with advancing age. Also, there are methods of prevention other than
antimicrobial prophylaxis or surgery in infants and young children who are at highest risk
for recurrent attacks of acute otitis media, such as advising the parents about the
following:
1. Breast-feeding, as opposed to bottle-feeding, is beneficial and thus is
recommended if more children are planned, because otitis media runs in
families (6).
2. No bottle-propping.
3. Supine, as opposed to prone, sleeping position.
4. Avoidance of smoking in the household.
5. No pacifiers past the age of 1 year.
6. Very importantly, no child day care, or a day-care facility with the fewest number
of children as possible.
The administration of vaccines, in addition to the child's standard vaccine schedule,
should be encouraged. The recently available pneumococcal conjugate vaccine (75)
should be given to all infants, but older children who have frequently recurrent attacks of
acute otitis media are also candidates. Influenza virus vaccination in the fall may reduce
the future attack rate (76).
If further methods of prevention are desirablethat is, if the frequency meets the entry
criteria used in the Casselbrant and colleagues trial (69), which are also the criteria
recently recommended by Dowell and associates (16)antimicrobial prophylaxis or
tympanostomy tubes can be recommended. If antimicrobial prophylaxis is the option
chosen, amoxicillin in the dosage regimen used in the Casselbrant and co-workers study
(69) is recommended. If the child is allergic to the penicillins, a daily dose of
sulfisoxazole 50 mg/kg body weight may be substituted. This prophylactic regimen
should be continued during the respiratory infection seasons (e.g., late fall, winter, and
spring). Children receiving prophylaxis should be examined at frequent and regular
intervals (every 1 or 2 months) to ensure that inapparent middle-ear effusion, which
might become chronic, does not occur. It is important to stress that prolonged
antimicrobial prophylaxis is inappropriate if long-standing persistent middle-ear effusion
(i.e., chronic otitis media with effusion) is present. In this case, surgical intervention
should be considered, such as myringotomy and tympanostomy tube insertion, with or
without adenoidectomy. Today, with the emergence of antibiotic-resistant otitic bacteria
(77), myringotomy and tube insertion appears to be a more reasonable alternative to
antimicrobial prophylaxis (78,79). Contrary to a widely publicized article by a utilization
review corporation in one of our leading journals, which failed to include recurrent acute
otitis media as an indication for tympanostomy tube insertion (80), this procedure has
been shown to be effective and is indicated in selected children today more than ever
(81). Also, postoperative otorrhea that occurs in some children following the placement
of tubes is usually associated with little or no otalgia (i.e., less severe) than acute otitis
media when the tympanic membrane is intact, is of short duration, and now can be safely
treated in most instances with an approved ototopical agent (82).
Adenoidectomy, with or without tonsillectomy, is frequently advocated for the prevention
of recurrent acute otitis media, but only two randomized, controlled trials have been
reported that addressed this problem, and only one showed efficacy of adenoidectomy,
albeit limited, for this condition. Paradise and co-workers (83) did demonstrate a
significant difference in the attack rate of acute otitis media in 99 children who had been
randomized to receive adenoidectomy compared with those who did not receive this
operation; all subjects in this clinical trial had at least one myringotomy and
tympanostomy tube insertion before random assignment. As a note of caution, however,
adenoidectomy in infants should be recommended only selectively (such as in infants
who also have severe nasal obstruction caused by obstructive adenoids) because this
operation carries some degree of increased risk in this age group.
In a more recently reported clinical trial by Paradise and co-workers (84), 461 children 3
to 15 years of age who had recurrent acute episodes, in which the rate was similar to the
previously performed clinical trial, but had neither ear nor throat surgery in the past, were
randomly assigned into one of three groups, if they were without recurrent throat
infection or tonsillar hypertrophy: adenoidectomy, adenoidectomy and tonsillectomy, or a
control group. If they had recurrent throat infections or tonsillar hypertrophy, or both,
they were randomized to receive only adenotonsillectomy or control. But, the outcome of
the trial revealed only limited and short-term efficacy of both adenoidectomy and
adenotonsillectomy and given the risks, morbidity, and costs of these procedures, neither
procedure is recommended as a first surgical intervention in children whose only
indication is recurrent acute otitis media.
In conclusion, and based on evidence from clinical trials, I recommend as the first
surgical procedure, when surgery is elected for prevention of frequently recurrent acute
otitis media, only myringotomy and tympanostomy tube insertion, and withhold
adenoidectomy unless the child meets the criteria for this procedure when moderate to
severe nasal obstruction is present. If recurrent acute otitis media persists following
spontaneous extrusion of the tympanostomy tubes, I will then recommend reinsertion of
the tympanostomy tubes, but also advise the addition of an adenoidectomy, irrespective
of adenoid size. Tonsillectomy is withheld unless the child meets criteria for
tonsillectomy (e.g., frequently recurrent throat infection, or upper airway obstruction) as
described above.
Chronic Otitis Media with Effusion
What evidence is there that myringotomy, with or without tympanostomy tube insertion,
is an effective procedure for treatment and prevention of chronic otitis media with
effusion? Mandel and colleagues (85) studied 109 Pittsburgh children with chronic
middle-ear effusion unresponsive to antimicrobial therapy. Our study revealed that
myringotomy and tympanostomy tubes provided more time free from otitis media and
better hearing than did myringotomy alone or nonsurgical control. Tympanostomy tubes
did cause troublesome otorrhea, however, and persistent perforation occurred in a few
patients. Each child had a follow-up of 3 years, during which only one myringotomy and
tympanostomy tube procedure was required in 50% of the subjects, but the remaining
50% required a second or third procedure; 30% required a second procedure; and 20%
required three operations. We also found that myringotomy had no advantage over no
surgery, and both had a high incidence of treatment failures. A second study reported
from Pittsburgh that followed the first trial, similar in design, confirmed the findings of
the first study (86).
The Agency for Health Care Policy and Research recently published their clinical
practice guideline on otitis media in young children, which recommended tympanostomy
tube insertion as an option when a young child has had bilateral otitis media with effusion
that persisted for at least 3 months with an associated hearing loss; if the effusion persists
for 4 months, tympanostomy tube placement is recommended (87). Even though this
guideline has many strengths as pointed out by Bluestone and Klein (88), one of its
weaknesses is to rely on one test of hearing as an indicator for surgery, when hearing has
been demonstrated to fluctuate over time when middle-ear effusion is present, as shown
by the trial conducted by Mandel and associates (85). We also recommend a trial of an
antimicrobial agent prior to recommending tympanostomy tube placement for chronic
otitis media with effusion, because they are effective, albeit for the short-term (89).
Related today to selection of an antimicrobial agent, a recently reported study of the
bacteriology of chronic middle-ear effusions stressed the importance of nonsusceptible S.
pneumoniae in the effusions (90). The guideline also stressed the importance of
improving the hearing in young children who had chronic otitis media with effusion,
citing concerns about child development, which still remains controversial (91,92). There
are other complications and sequelae associated with otitis media (93), and recurrent and
chronic otitis media with effusion may have an impact on the child's quality of life (94).
Indeed, a recent study of tympanostomy tube surgery was associated with an
improvement in the quality of life in children following insertion (95).
Table 82.3 lists the indications for myringotomy and tympanostomy tube placement. A
controversy has arisen related to the use a flash-scanner CO
2
laser for myringotomy as an
alternative to the traditional cold-knife myringotomy, in an attempt to provide longer
middle-ear ventilation and thus the need for tympanostomy tube insertion. The procedure
is advocated as an alternative to not only tympanostomy tube placement, but avoidance of
a general anesthetic in infants and children, which can be performed as an office
procedure. First, myringotomy aloneeither with the traditional cold knife or with a
laseris not the management of choice for prevention of recurrent acute otitis media.
The clinical trial by Casselbrant and colleagues (69) showed that in infants and young
children the method for prevention, such as antimicrobial prophylaxis (or tympanostomy
tube), should continue for at least 1 year. Related to the merits of using a laser
myringotomy for acute otitis media or chronic otitis media, a randomized clinical trial
should be conducted to demonstrate the safety and efficacy of the laser compared with
the standard method; to date, no such trial has been performed. In an effort to determine
the efficacy of laser myringotomy, in addition to an adenoidectomy for chronic otitis
media with effusion, Szeremeta and co-investigators (96) reported the rate of
postoperative recurrence of middle-ear effusion to be the same as when a cold-knife
myringotomy was used in a previously treated group of patients (i.e., historical controls).
Brodsky and colleagues (97) reported modest success in using this laser to perform the
myringotomy prior to placement of a tympanostomy tube, as an office-based procedure.
The local anesthesia and patient compliance are the keys to performing a myringotomy
and tympanostomy tube insertion in an office setting, not the use of a laser, which has a
significant cost. Cooperative older children, adolescents and adults are potential
candidates for this type of procedure using the standard methods. Appropriate
randomized clinical trials are needed to evaluate the safety and efficacy of laser
myringotomy, with or without tympanostomy tube placement. Until then, the traditional
methods are recommended.

TABLE 82.3. INDICATIONS FOR
MYRINGOTOMY AND PLACEMENT OF
TYMPANOSTOMY TUBES



As a way to prevent otitis media, adenoidectomy with and without tonsillectomy has been
evaluated in several clinical studies during the past 30 years (98,99,100 and 101), but
only during the past few years have well-controlled randomized clinical trials been
reported. Maw (102) evaluated adenoidectomy with and without tonsillectomy in 103
children from Bristol, England, who had chronic middle-ear effusion. This study showed
that adenoidectomy was more effective than no surgery and that the efficacy of
adenotonsillectomy did not add substantially to the efficacy of adenoidectomy alone. In a
subsequent trial, Gates and colleagues (103) studied 578 Texas children 4 to 8 years of
age, all with chronic middle-ear effusion unresponsive to antimicrobial therapy. Their
study showed adenoidectomy and myringotomy, with and without tympanostomy tube
insertion, to be more effective than myringotomy with or without tube insertion;
myringotomy had the worst outcome (Table 82.4). Paradise and colleagues (83) studied
99 Pittsburgh children whose otitis media recurred after their tympanostomy tubes
spontaneously extruded. We showed that for selected at-risk children, all with previous
tubes, the efficacy of adenoidectomy was definite but limited over a 2-year period. The
effect was greater for middle-ear effusion than for recurrent acute otitis media (Table
82.5).

TABLE 82.4. EFFECTIVENESS OF VARIOUS
TREATMENTS IN 578 CHILDREN WITH
CHRONIC OTITIS MEDIA WITH EFFUSION



TABLE 82.5. EFFICACY OF ADENOIDECTOMY
FOR RECURRENT OTITIS MEDIA IN CHILDREN
PREVIOUSLY TREATED WITH
TYMPANOSTOMY PLACEMENT



To summarize these clinical trials that assessed the efficacy of surgical options for
management of chronic otitis media with effusion, the study by Maw (102) demonstrated
that adenoidectomy was more effective than no surgery and that adenoidectomy without
tonsillectomy was about equal in efficacy to tonsillectomy and adenoidectomy for
chronic middle-ear effusion. The trial conducted by Paradise and associates (83) showed
that adenoidectomy and myringotomy and tube insertion were more effective than
myringotomy and tube insertion alone. The study by Gates and colleagues (103) showed
that adenoidectomy and myringotomy with or without tube insertion were more effective
than myringotomy with or without tube insertion. These investigators concluded that
adenoidectomy and myringotomy should be recommended over adenoidectomy and
myringotomy with tube insertion because of the high incidence of otorrhea through the
tube. In the adenoidectomy groups, however, when recurrent otitis media occurred after
the procedure, it occurred earlier when only a myringotomy was performed (compared
with the group who also had a tympanostomy tube inserted). Although all three
randomized clinical trials of adenoidectomy for otitis media failed to demonstrate a
relationship between adenoid size and outcome, it is possible that adenoids may obstruct
the eustachian tube or that nasal obstruction caused by obstructive adenoids may impair
tubal function (Fig. 82.1) (83,102,104). A possible alternative, or additional, explanation
for the success of adenoidectomy in the management of otitis media (both recurrent acute
and chronic otitis media) is that the adenoids harbor potential pathogens, such as H.
influenzae, that can gain access to the middle ear through the eustachian tube, which can
be resistant to the standard antibiotics (105,106).

FIGURE 82.1. Two proposed mechanisms by which
obstructive adenoids could alter eustachian tube function.
Adenoids could compress the tube in the fossa of
Rosenmller (i.e., extrinsic obstruction). Obstruction of
the posterior nasal choanae could result in abnormal
nasopharynx pressures during swallowing (i.e., Toynbee
phenomenon), which in turn either prevent tubal opening
or insufflate nasopharyngeal secretions into the middle
ear. [Reprinted from Bluestone CD, Klein JO. Otitis media in infants and children, 3rd
ed. Philadelphia: WB Saunders, 2000 (in press).]



In conclusion, and based on evidence from clinical trials, I recommend as the first
surgical procedure, when surgery is elected for management of chronic otitis media with
effusion, unresponsive to a course of antimicrobial therapy, only myringotomy and
tympanostomy tube insertion, and withhold adenoidectomy unless the child meets the
criteria for this procedure when moderate to severe nasal obstruction is present. If chronic
otitis media with effusion recurs following spontaneous extrusion of the tympanostomy
tubes, I will then recommend adenoidectomy, irrespective of the size of the adenoids, and
a myringotomy and aspiration of the middle-ear effusion. Reinsertion of the
tympanostomy tubes is undertaken on an individualized basis related to age of the patient
(more likely in younger children than older), concerns about another general anesthetic if
chronic otitis media with effusion recurs despite the adenoidectomy and myringotomy,
and the wishes of the parents after they have been informed about the risks and benefits
of placement of tympanostomy tubes versus not inserting tubes, at this stage.
Tonsillectomy is withheld unless the child meets criteria for tonsillectomy (e.g.,
frequently recurrent throat infection or upper airway obstruction), as described above.
Clinical Decision Making
Much information has been derived from randomized clinical trials over the past decade
about the indications for surgery for otitis media; however, their specific entry criteria
excluded many patients. Therefore, decisions for or against surgical intervention
(myringotomy/tympanostomy tube/adenoidectomy/tonsillectomy) should be
individualized according to the following guidelines:
1. Assess the frequency, duration, and severity of otitis media (including the degree
of hearing loss).
2. Determine whether the child has received appropriate, adequate medical
management.
3. Determine whether the child had a failure of antimicrobial prophylaxis.
4. Determine the rate of antibiotic-resistant bacterial otitis media pathogens in the
community. Table 82.6 lists some factors in the decision-making process.

5. TABLE 82.6. FACTORS IN THE
DECISION-MAKING PROCESS FOR
OR AGAINST SURGERY FOR
RECURRENT ACUTE OTITIS
MEDIA OR CHRONIC OTITIS
MEDIA WITH EFFUSION
6.


The patient's age may be important because in the usual operative setting tonsillectomy
and adenoidectomy is somewhat riskier in infants. The clinical practice guideline on otitis
media in young children (87) does not recommend adenoidectomy in children under 4
years of age, even though the clinical trial by Paradise and associates (83) did include this
age group and the procedure was effective; all children had one or more tympanostomy
tube insertions prior to entering the trial (88). Most clinicians would not recommend
surgery on the pharynx (tonsillectomy, adenoidectomy, or both) for children who are an
anesthesia risk, unless the child has severe upper respiratory tract obstruction. Likewise,
the season of the year may be a factor. An older child with otitis media may want to
engage in competitive swimming, which would make insertion of tympanostomy tubes
less desirable. Other indications for surgery on the ears or pharynx that make the decision
for performing ear/pharyngeal surgery more compelling include deformation of the
eardrum (e.g., a deep retraction pocket), presence of sleep apnea resulting from
obstructive tonsils or adenoids, and frequently recurrent tonsillitis. Also, patients in
special populations (such as children with cleft palate or Down syndrome) may benefit
more from insertion of tympanostomy tubes than from watchful waiting.

HIGHLIGHTS
Controversy remains over the indications for tonsillectomy,
adenoidectomy, myringotomy, and tympanostomy tube surgery,
despite recently reported randomized clinical trials that
addressed the effectiveness of these operations.
Severe upper airway obstruction caused by hypertrophy of the
tonsils or adenoids or both resulting in sleep apnea or cor
pulmonale or both is a certain (or definite) indication for
tonsillectomy and adenoidectomy.
Documenting the frequency, severity, and duration of tonsillitis
is an important factor in the decision-making process for
tonsillectomy.
Tonsillectomy was effective in reducing the number of
frequently recurrent throat infections in a randomized clinical
trial.
An unproved but potentially important hypothesis is that a -
lactamase enzyme from bacteria that can be isolated from the
core of recurrently infected tonsils could interfere with
penicillin's activity against S. pyogenes.
Despite the lack of conclusive evidence from randomized
clinical trials, elective tonsillectomy may be effective for
chronic tonsillitis and peritonsillar abscess. In the absence of
sleep apnea or alveolar hypoventilation resulting in cor
pulmonale, the efficacy of adenoidectomy for relief of nasal
obstruction attributable to obstructive adenoids remains
uncertain; however, olfaction as well as hyponasal speech may
be improved.
Adenoidectomy was effective in preventing chronic otitis media
with effusion in three randomized clinical trials conducted in
England, Texas, and Pittsburgh; the latter trial also showed
efficacy in preventing recurrent attacks of acute otitis media in
patients who had had tympanostomy tubes in the past, but a
subsequent trial failed to reveal efficacy of adenoidectomy,
with or without tonsillectomy, in children who had not received
tubes in the past. The efficacy of tympanostomy tubes for
prevention of recurrent acute otitis media and chronic otitis
media with effusion also has been demonstrated in clinical
trials, three of which were conducted in Pittsburgh. Despite the
evidence that both adenoidectomy and myringotomy tube
insertion are effective, decisions for or against surgical
intervention should be individualized for the patient with
recurrent acute otitis media or chronic/recurrent otitis media
with effusion.
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102. Maw AR. Chronic otitis media with effusion (glue ear) and adenotonsillectomy: prospective
randomized controlled study. BMJ 1983;287:15861588.
103. Gates GA, Avery CA, Prihoda TJ, et al. Effectiveness of adenoidectomy and tympanostomy tubes
in the treatment of chronic otitis media with effusion. N Engl J Med 1987;317:14441451.
104. Gates GA, Avery CA, Prihoda TJ. Effect of adenoidectomy upon children with chronic otitis
media with effusion. Laryngoscope 1988;98:5863.
105. Suzuki M, Watanabe T, Mogi G. Clinical, bacteriological, and histological study of adenoids in
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

83 CONGENITAL ANOMALIES OF THE AERODIGESTIVE TRACT
Head & Neck SurgeryOtolaryngology
83




CONGENITAL ANOMALIES OF THE
AERODIGESTIVE TRACT
GERALD B. HEALY

G.B. Healy: Department of OtolaryngologyHead and Neck Surgery, Children's Hospital, Boston,
Massachusetts.


Anatomy and Physiology
Evaluation and Diagnosis
Physical Examination
Radiologic Evaluation
Endoscopic Evaluation
Anomalous Conditions
Nose
Oropharynx
Larynx
Trachea
Esophagus
Suggested Reading
ANATOMY AND PHYSIOLOGY
The developmental anatomy of the upper aerodigestive tract begins with fertilization and
continues through infancy into adulthood. The embryonic period proper includes the first
8 postovulatory weeks of development and is followed by the 32-week fetal period. The
embryonic period has been divided into 23 stages or levels of development, which are
characterized by the appearance of specific morphologic features. It is marked by a
highly complicated form of cellular interaction with resultant organ formation.
The upper aerodigestive tract is generally considered to include the nasal cavity,
nasopharynx, oropharynx, hypopharynx, larynx, tracheobronchial tree, and esophagus.
The major portion of nasal development occurs between approximately weeks 3 and 8
(stages 9 to 23), whereas the first indication of the respiratory system occurs at about the
20th day (stage 9) with the appearance of the median pharyngeal groove (Fig. 83.1). At
day 22 (stage 10) the pharynx first appears as a distinct entity, as do the laryngotracheal
sulcus and the pulmonary primordium. The right and left lung begin to divide at about
day 24 (stage 11). By the 26th day (stage 12) the digestive and respiratory tubes begin to
pursue independent courses, and by the 28th day (stage 13) the trachea becomes
identifiable. During this time the esophagus is also pursuing an independent course,
having made its first appearance at about day 21 (stage 10). Most true developmental
anomalies probably have their origin during this critical period of organogenesis.

FIGURE 83.1. Fetal development of the aerodigestive
tract beginning at 5.5 weeks. Note the appearance of the
median pharyngeal groove. Progressive embryologic
development demonstrates specific refinement of the air
and food passages.



The upper aerodigestive tract also has an intimate relationship with the derivatives of the
dorsal ventral aorta, which explains the potential for congenital vascular anomalies to
produce pathology related to the upper airway.
Certain features of the pediatric airway are unique. The larynx is located significantly
higher in the infant: the inferior margin of the cricoid cartilage resides at about the second
cervical vertebra at birth and descends to the level of the seventh cervical vertebra in the
adult. The relationship of the hyoid bone to the thyroid cartilage also changes with
normal growth and development. In the child there is close approximation of the larynx
to the hyoid, which may be particularly exaggerated in certain congenital abnormalities
such as the Pierre Robin syndrome (Fig. 83.2). Even in the normal infant, however, the
larynx is more anterior and superior in the neck than it is in the adult. This high position
brings the epiglottis and the palate into close proximity and tends to make the child a
necessary nose breather in the first few months of life. The epiglottis in the newborn may
act as a bridge and thus may make the larynx more of an intranarial organ. The fact that
the infant is an obligate nose breather during the first few months of life may have
potential clinical significance with various congenital anomalies of the nasal airway.

FIGURE 83.2. Contrast between the adult and pediatric
larynx. Note that the pediatric larynx is higher and has a
closer association to the hyoid and thus to the base of the
tongue. This produces a more anterior displacement of
the larynx, which is particularly important in terms of
endoscopic evaluation as well as intubation.



The infant larynx obviously differs greatly in size from that of its adult counterpart. The
vocal cords are about 6 to 8 mm long; about half the vocal cord is cartilaginous. The
glottic opening of the newborn measures about 7 mm in the anteroposterior (AP)
dimension and has a posterotransverse dimension of 4 mm. The subglottic AP diameter is
usually 5 to 7 mm at birth. The tracheal diameter varies from 3 mm in the premature
infant to about 25 mm in the adult. Tracheal rings are usually about 2 mm wide, and there
are about four rings per centimeter of trachea in the normal infant. The total number of
tracheal rings varies between 18 and 20. The average distance between the glottis and the
tracheal bifurcation ranges from 5.7 cm at birth to about 8.1 cm at 15 months. In the child
the relationship of the skin to the trachea is not parallel but is angled about 60 degrees.
These dimensions are critical when assessing a child's airway for congenital or acquired
anomalies.
EVALUATION AND DIAGNOSIS
Most infants with congenital anomalies of the aerodigestive tract present with stridor or
feeding difficulties. In certain pathologic conditions both may be present.
Noisy breathing presents a puzzling and challenging diagnostic dilemma for the primary-
care physician and the consulting otolaryngologist. Normally respiration does not
produce audible sounds. Noise patterns are produced by the partial obstruction of air
passage into and out of the respiratory system. It may be loud or soft and high- or low-
pitched, depending on the type and extent of the obstruction and the resulting flow
dynamics. The timing and quality of the stridor are valuable diagnostic clues in
determining the level of airway pathology.
Careful documentation of the phase of respiration when stridor is most intense is
imperative. In addition, a careful history must be obtained and a precise physical
examination completed. The stethoscope is useful in documenting stridor. In many
infants with airway obstruction, the respiratory rate is quite high; thus, the examiner's ear
may be fooled without this aid. The presence of stridor on inspiration or expiration may
vary depending on the location and degree of obstruction present. Stridor that is purely
inspiratory is commonly indicative of lesions in the more superior part of the upper
airway. If the expiratory component is most prominent, the obstruction usually lies distal
to the vocal cords. Biphasic stridor often indicates subglottic pathology, although
occasionally glottic pathology may present in this way.
Careful analysis of the quality of the stridor may help identify a specific anatomic
location. For example, inspiratory stridor of a sonorous or snoring nature usually results
from lesions of the nose or nasopharynx. A more high-pitched inspiratory stridor is
commonly secondary to pathology at the supraglottic level. Congenital anomalies of the
air and food passages are numerous and are listed in Table 83.1.

TABLE 83.1. COMMON CONGENITAL
ANOMALIES OF THE AERODIGESTIVE TRACT



The evaluation of the infant with stridor often produces discussion as to the most
appropriate method of management. The rapidity with which the diagnostic evaluation is
performed is dictated by the patient's general physical condition. An ideal evaluation may
be impossible if severe respiratory obstruction is present.
The evaluation begins with a detailed and precise history from the parents and anyone
else who has had intimate contact with the patient. In a newborn, detailed information
from the nurses caring for the patient may be important. In fact, a careful history points to
the diagnosis in more than 85% of cases.
The age of onset of symptoms is often critical. Immediate respiratory distress at birth
with obvious audible stridor is usually secondary to a true congenital lesion such as
choanal atresia or congenital subglottic stenosis. Stridor appearing several weeks after
birth may be more consistent with congenital pathology such as laryngomalacia or
subglottic hemangioma. Inflammatory disorders almost never affect the newborn; thus,
most stridor or respiratory distress appearing in the first few weeks of life may be
assumed to be secondary to a congenital lesion.
The intensity and persistence of stridor is important from a diagnostic standpoint. The
sudden appearance of intense stridor usually points toward inflammation, trauma, or a
foreign body, especially in the toddler age group. A change in severity is also an
important historical detail. Stridor that gradually increases in severity may indicate an
expanding lesion or even a neoplasm such as a congenital cyst or papilloma, whereas
difficulty noted during exertion may be more diagnostic of a fixed lesion that may not be
causing significant obstruction, such as a hemangioma or mild subglottic stenosis.
The relationship of positional change to the patient's symptoms is another important
diagnostic feature. In newborns with high-pitched inspiratory stridor secondary to
supraglottic pathology, the prone position may be more desirable. Hyperextension of the
neck and thrusting of the chin to a more forward (sniffing) position may indicate an effort
to straighten the airway, as in extrinsic vascular compressions of the trachea.
A careful feeding history also must be obtained. Lesions of the nasal cavity, nasopharynx,
and pharynx are more likely to cause feeding difficulties than those in the intrinsic
airway. Exceptions to this may be the patient with a vascular anomaly compressing both
the trachea and the esophagus, or the patient with a true communication of these
structures, such as a tracheoesophageal fistula. An associated cough may indicate an
anatomic communication between the esophagus and trachea or an inadequate neurologic
pathway, as in vocal cord paralysis.
After a thorough history is taken, the upper aerodigestive tract is examined. There are
three major areas of investigation: the physical examination, the radiographic
examination, and endoscopic confirmation.
PHYSICAL EXAMINATION
The patient must be carefully observed before being touched. The physician notes the
child's position, color, level of consciousness, respiratory rate, and the presence or
absence of retractions. If time allows, the parents should be questioned during the
observation period regarding the presence or absence of difficulties in any of these areas
before the examination.
The child's general physical condition is noted, including the presence or absence of
congenital anomalies in the head and neck area, such as craniofacial malformations or
mass lesions.
The neck and chest are auscultated to identify the phase and quality of the stridor and to
determine if there is evidence of associated pulmonary pathology (this obviously includes
symmetry of breath sounds). The quality of the patient's cry and the presence or absence
of cough are noted. The lack of cry may indicate glottic pathology such as congenital
web.
The patient's position may be an important clue in locating the site of obstruction. Airway
distress secondary to intrinsic laryngeal or tracheal pathology is usually not relieved by
changes of position. Infants with definite congenital abnormalities of the supraglottic
larynx may prefer the prone position, which allows the larynx and supraglottic structures
to fall forward.
The patient's color often helps determine the level of oxygenation. Circumoral pallor or
cyanosis may be the first sign of hypoxia. This finding does not necessarily represent a
respiratory problem, however, because it also may be seen in patients with cardiac
anomalies.
Normal functions such as nasal respiration and swallowing are evaluated. In the newborn,
it is important to ascertain whether airflow is present in the nasal cavities. There are
numerous methods of ascertaining patency of the nasal airway, including passing nasal
catheters or holding small nasopharyngeal mirrors in front of the nares. Often patients
with supraglottic or oropharyngeal obstruction or esophageal anomalies have difficulty
swallowing secretions; thus, drooling can be an important diagnostic clue to lesions in
this area.
The actual hands-on examination must be performed with extreme caution. Gentle
manipulation of the oral cavity and mandible may help determine whether oropharyngeal
obstruction is present. Carefully pulling the tongue or jaw forward may give some relief
to patients with problems in this area. The examiner must be careful not to agitate or
excite the child who already shows any evidence of hypoxia: this merely increases the
work of breathing and does little to help establish the diagnosis.
The assessment continues with careful palpation of the neck to identify normal
landmarks. The trachea may be located slightly to the right of the midline in the newborn.
Deviation may occur with respiration as the mediastinum shifts secondary to
overinflation or underinflation of one lung. Fixed deviations may indicate the presence of
a mass lesion in the mediastinum or in structures adjacent to the trachea, such as the
thyroid. Large congenital anomalies involving the neck, such as lymphatic malformation,
may be large enough to cause extrinsic compression of the hypopharynx or trachea. Such
masses are usually readily apparent on physical examination.
After completing these phases of the examination, the consultant should have some
reasonable differential diagnosis in mind. This determines the next step in the evaluation
process. In the patient with mild symptoms and minimal distress, immediate visualization
in the nursery or office setting may be contemplated. This is usually done with flexible
fiberoptic instrumentation. In these cases radiologic assessment also may be planned in a
systematic and orderly manner. In more severe cases with significant obstruction, rigid
examination in the operating room is usually more appropriate. Whether a concomitant
radiologic assessment is feasible is determined by the severity of the distress and the
consultant's clinical judgment.
The flexible fiberoptic laryngoscope has proved to be a valuable tool in assessing the
nasopharynx, hypopharynx, and larynx. With the advent of the flexible fiberoptic
bronchoscope, the tracheobronchial tree also has become accessible to this method of
evaluation. The flexible fiberoptic laryngoscope gives vital information on the neurologic
status of the larynx as well as the dynamic function of the hypopharynx and supraglottis.
The optics on the small-diameter flexible instruments are still somewhat suspect,
however. This equipment also does not allow the examiner to appreciate depth of field;
thus, subtle lesions such as tracheoesophageal fistula or laryngeal cleft may be
overlooked. Video and still photographic documentation is feasible and should be used
when possible for future review. Appropriate resuscitative equipment must be available
in any setting where this equipment is used.
If flexible fiberoptic laryngoscopy is contemplated, infants should be placed in the
semisitting position to allow the larynx to fall somewhat anteriorly and permit better
visualization of the glottic structures.
Flexible evaluation of the esophagus may be quite useful in documenting structural
abnormalities as well as pathologic conditions affecting mucosal integrity. In young
infants this evaluation should be undertaken with appropriate airway protection.
RADIOLOGIC EVALUATION
If the clinical situation permits, a thorough radiologic assessment of the upper airway,
chest, and esophagus should be undertaken in any patient with evidence of congenital
pathology of the aerodigestive tract. Anteroposterior and lateral films of the neck and
chest should be part of the diagnostic profile. If possible, inspiratory and expiratory films
are preferable so that comparisons can be made.
Fluoroscopy is also desirable and may help answer questions regarding the constancy of
findings on static films. Fluoroscopy with contrast in the esophagus should be strongly
considered in any patient with suspected aerodigestive pathology. These studies may help
define vascular compressions, fistulae between the trachea and esophagus, and neurologic
difficulties that lead to aspiration or discoordination of the pharynx during swallowing.
Computed tomography (CT) is not especially helpful in identifying lesions of the upper
airway in newborns; the single exception is to delineate choanal stenosis or atresia.
Magnetic resonance imaging seems helpful in defining lesions of the upper airway in
children. It has already proved useful in identifying vascular anomalies that compress the
trachea or esophagus. Spiral CT angiography and three-dimensional deconstruction
methods represent new noninvasive tools in the diagnosis of vascular rings and associated
tracheobronchial anomalies in children. The use of ultrasonography in the airway is
evolving slowly.
ENDOSCOPIC EVALUATION
Endoscopic evaluation continues to be the mainstay in establishing a definitive diagnosis
in any patient suspected of having a congenital anomaly of the upper aerodigestive tract.
It requires precision, skill, diligence, and cooperation with other members of the
endoscopic team (in most cases, the endoscopist, anesthesiologist, and radiologist).
Appropriate instrumentation must be available, including a complete selection of rigid
and flexible laryngoscopes, bronchoscopes, and esophagoscopes. Appropriate magnifying
telescopes should be available, together with still photography and video cameras for
documentation.
The use of endoscopy varies from examiner to examiner. On one end of the spectrum are
those who feel that the airway may be evaluated radiologically with an AP and lateral
soft-tissue radiograph of the neck, an AP and lateral chest radiograph, and a barium
esophagogram. This is usually coupled with a fiberoptic examination to evaluate the
nose, nasopharynx, pharynx, supraglottic, and glottic regions. At the other end of the
spectrum are those who would use a complete radiologic examination coupled with a
flexible examination of the nose, pharynx, and larynx, as well as rigid endoscopic
evaluation of the larynx, tracheobronchial tree, and esophagus. Whichever method is
used, all procedures should be undertaken in a safe setting with resuscitative equipment
available. A complete evaluation of the aerodigestive tract is necessary because there
may be more than one congenital lesion in the region. About 12% to 18% of patients
have simultaneous lesions affecting different areas of the airway.
Topical anesthesia is often helpful, whether the patient is evaluated awake or under
general anesthesia. Lidocaine (0.5%) is used for this purpose in the nasal cavity,
hypopharynx, and larynx.
I prefer the method of complete assessment of the airway in the operating room in
conjunction with appropriate radiologic examination. The examination begins with the
awake infant held in the semisitting position with the head stabilized. A flexible
laryngoscope is passed through each side of the nasal cavity to examine the patency of
the nasal airway. The scope is then passed into the nasopharynx, where anatomy and
patency are evaluated. The dynamic function of the palate is also assessed. The scope is
then advanced to evaluate the hypopharynx and supraglottic structures as well as the
mobility of the vocal cords bilaterally. At this point the dynamic motion of the larynx is
documented to rule out such conditions as laryngomalacia or vocal cord paralysis.
General anesthesia is then induced using a mask inhalation technique, with positive-
pressure ventilation to assist the respiratory effort when necessary. Time must be taken to
achieve an appropriate plane of anesthesia. The patient must be sufficiently anesthetized
to negate laryngeal reflexes but also should be able to breathe spontaneously. If a fixed
obstruction is present, a longer time may be necessary to achieve the appropriate level of
anesthesia than in the patient with a completely patent airway.
The larynx is visualized and 0.5% lidocaine is topically applied. After appropriate
oximeter and electrocardiographic leads have been applied and an intravenous line
inserted, the formal endoscopy begins. The shoulders are elevated and the head is raised
and somewhat hyperextended (Fig. 83.3). In very young infants it may be necessary to
flex the head forward to allow the more anteriorly placed larynx to achieve a more
posterior position for clear visualization. The gingiva is protected with a wet gauze and
the laryngoscope is inserted to inspect the oropharynx, hypopharynx, and larynx. The
fiberoptic telescope is valuable at this point for documentation and better magnification
(Fig. 83.4). The supraglottic, glottic, and subglottic structures also may be evaluated with
this instrument. Care must be taken to insert the laryngoscope into the posterior
commissure to rule out a laryngeal cleft.

FIGURE 83.3. The appropriate position for the child and
young adult for endoscopic evaluation. The shoulders are
elevated and the head is raised and somewhat
hyperextended. This allows for appropriate insertion of
the bronchoscope and direct visualization by the
endoscopist.



FIGURE 83.4. The patient is appropriately positioned for
use of the fiberoptic telescope through an already
positioned bronchoscope.



During this phase of the examination the patient should be allowed to breath
spontaneously; in fact, a small catheter may be placed through the nose into the
hypopharynx for appropriate insufflation of oxygen and anesthetic gas. Careful
monitoring of the oximeter is mandatory; if oxygen levels decrease, the laryngoscope is
removed and mask ventilation is continued until appropriate oxygenation is achieved.
At this point an appropriate-size bronchoscope is chosen and carefully inserted to inspect
the tracheobronchial tree. A magnifying telescope is inserted through the bronchoscope
for better visualization. Some examiners insert the telescope alone and allow spontaneous
ventilation; this is acceptable but requires extreme diligence and the cooperation of the
anesthesiologist and the endoscopist.
Once these phases of the examination are completed, the airway is secured by intubation
and a complete evaluation of the esophagus is undertaken with the rigid esophagoscope
coupled with appropriate telescopes. Flexible esophagoscopy may be substituted if the
examiner desires.
A flexible bronchoscope may be used in young infants. However, it does not give the
same depth of field or precise magnification of the rigid scope, and thus I find it
somewhat less desirable.
When the examination is completed, the physician must decide whether the airway can
maintain ventilation without assistance or whether an artificial airway must be placed (an
endotracheal tube or tracheotomy tube). This depends on the degree of obstruction, the
nature of the pathology, and the endoscopist's clinical judgment.
ANOMALOUS CONDITIONS
Management of the more common conditions of the aerodigestive tract (Table 83.1) is
outlined below, but many of the principles noted can be applied to the less common
entities.
Nose
Choanal Atresia/Stenosis
Management depends heavily on CT evaluation of the nasal cavity and choana. Patients
with a significant bony component to the atresia or significant bony narrowing of the
nasal cavity are best corrected by surgery via a transpalatal approach. Transnasal
endoscopic correction is usually best suited to those patients with membranous atresia,
although there is some merit to this approach in cases where the bony component is thin.
Mild anterior and posterior stenosis is usually best managed with a conservative
approach, which includes the use of mucosal decongesting agents and watchful waiting.
An oral airway may be supplemented in young children, especially during sleep, until the
nasal cavity has a chance to mature.
Septal Deformity
Deformities of the nasal septum often go unrecognized in newborns. Cases that cause
severe respiratory distress may be identified during a routine nasal examination.
Treatment consists of septal repositioning so that the cartilaginous structures may mold
into a normal position along the nasal crest. The use of a topical decongestant also may
be indicated in the acute period until the initial swelling from the reduction has passed.
Oropharynx
Masses and Cysts
The base of the tongue and the vallecula region are the most common part of the
oropharynx affected by congenital anomalies in the newborn. Lesions in this area include
lingual thyroid, thyroglossal duct cyst, and vallecula cyst. A transoral approach to all of
these lesions is usually possible. Definitive treatment is necessary in all cases due to the
unpredictability of pathology in this area.
A median glossotomy offers a satisfactory approach to the base of the tongue in the
newborn and is extremely useful in removing obstructive lesions in this area (Fig. 83.5).
In patients with lingual thyroid, consultation with the endocrinologist is necessary to
determine the need for possible replacement therapy, should this be the patient's only
functioning thyroid tissue.

FIGURE 83.5. A: Magnetic resonance imaging scan
showing thyroglossal duct cyst at the base of the tongue
(arrow). B: Lesion at tongue base (arrow). C: A median
glossotomy is used to access this lesion while avoiding an
external excision. D: Excised thyroglossal duct cyst.



Larynx
Supraglottis
Laryngomalacia
Congenital flaccid larynx (laryngomalacia) accounts for a significant proportion of the
congenital laryngeal anomalies in the newborn. This condition is secondary to flaccidity
and incoordination of the supraglottic cartilage and mucosa of the arytenoids,
aryepiglottic folds, and epiglottis. Traditionally patients with this entity have few
symptoms at birth, but over the first few weeks of life gradually develop high-pitched
inspiratory stridor and occasional feeding difficulties. The diagnosis must be made while
observing the functioning larynx; thus, observation in the awake patient is ideal.
Reassuring the parents remains the mainstay of treatment in most cases, because the
condition is usually self-limited. Complete resolution may take as long as 18 months.
Rarely, intervention may be necessary, either by placing a tracheotomy or performing a
supraglottoplasty.
Neoplasm
Benign neoplasms may present in the supraglottis within the first few days or weeks of
life. The most common lesions are vascular malformations. These are more commonly
classified as hemangioma or lymphatic malformations. If the process progresses
significantly, airway obstruction may be precipitated. Management usually involves
relieving the acute obstruction by placing a tracheotomy. Often the full dimensions of the
lesion may not be appreciated for several months after birth; thus, premature intervention
may prove unrewarding in the long term.
Glottis
Vocal Cord Immobility
Vocal cord immobility may present unilaterally or bilaterally. Most unilateral lesions are
idiopathic and often self-limited. In these circumstances the infant presents with a hoarse
or weakened cry but rarely has airway distress. In bilateral immobility the cry is usually
normal but stridor may be present, especially when the patient is stressed. A chest
radiograph is an important part of the evaluation, to rule out mediastinal or cardiac
anomalies. Patients with bilateral immobility also should have a thorough neurologic
examination and an imaging study of the brain to rule out hydrocephalus and the Arnold-
Chiari malformation; both are common findings in patients with bilateral vocal cord
paralysis. Tracheotomy may be necessary, especially if stridor is constant. In unilateral
cases, management consists of watchful waiting. Because most cases are self-limited,
intervention is unnecessary if no thoracic lesion is present.
Web
Webs most commonly affect the anterior portion of the glottis. They may be of varying
thickness and sometimes extend into the subglottic space for a varying distance. Most
commonly the infant presents with aphonia, which is often the clue to the diagnosis.
Therapy is usually dictated by the amount of obstruction present at the glottic level. Webs
occupying more than 50% of the glottis require treatment, which consists of lysis in the
case of a thin web and the placement of a tracheotomy in patients with a thicker web,
especially if there is subglottic extension. In these cases the compromised airway usually
does not withstand the effects of an upper respiratory infection with secondary mucosal
edema.
Formal correction may take place anywhere after the sixth month of life, either by
external thyrotomy or internal lysis with the CO
2
laser. In severe cases a keel should be
placed for about 2 to 3 weeks while reepithelialization of normal structures takes place.
In some patients with moderate webs an endoscopic lysis can be undertaken and the
patient kept nasally intubated for 3 to 4 days. The endotracheal tube acts as a keel and
keeps the cords apart enough to prevent them from readhering.
Subglottis
Congenital Stenosis
Congenital subglottic stenosis occurs secondary to a deformity of the cricoid cartilage.
This lesion may present with varying degrees of severity. A subglottis with an AP
diameter of less than 4 mm is usually diagnostic of the lesion. In severe cases the infant
usually presents with severe stridor and airway distress soon after birth. In milder cases
symptoms may not appear until the first upper respiratory infection. The tip-off in these
patients may be recurring stridor in conjunction with most respiratory infections in the
first few years of life. Because these episodes may mimic croup, the diagnosis may be
overlooked unless the primary-care physician and consultant are alerted to the historical
facts.
In mild cases treatment may be directed solely toward the pathology noted during upper
respiratory infections. Medical therapy in the form of racemic epinephrine,
corticosteroids, and antibiotics limits the course of the acute process in most patients. In
severe cases, anterior cricoid decompression (cricoid split) may be used. The other
alternative is the placement of a tracheotomy until the patient reaches about 12 to 15 kg,
at which point the cricoid may be augmented by a cartilage graft.
Hemangioma
Isolated subglottic hemangioma usually does not present during the first few weeks of
life (Fig. 83.6). The typical patient develops biphasic stridor at some point after the third
week of life that worsens with exertion or agitation. Rarely, a slight feeding difficulty
may be present. About 50% of patients have an associated cutaneous hemangioma.
Radiologic assessment often shows an asymmetric impingement on the subglottic space
due to this compressible lesion. Spontaneous regression often occurs after the 12th to
18th month.

FIGURE 83.6. Isolated subglottic hemangioma
appearing just below the vocal cords. Note the staining,
which is characteristic of this lesion (arrow).



In patients with severe obstruction, treatment is directed toward decompression of the
subglottic space. This involves either the immediate use of the CO
2
laser to vaporize the
lesion or the placement of a tracheotomy to bypass the obstruction. The former seems
more desirable.
Posterior Cleft
This rare anomaly occurs because the tracheoesophageal septum fails to develop. Clefts
may be of varying degrees of severity, ranging from a mere notching of the interarytenoid
space to a full-blown laryngotracheoesophageal communication. Newborns often present
with immediate feeding difficulties and secondary pneumonitis and evidence of
aspiration. A careful esophagogram is usually diagnostic, showing the obvious
appearance of contrast material in the trachea. However, the diagnosis is best made by
endoscopy.
Mild cases usually require no treatment, because the supraglottic sphincter mechanism of
the larynx will protect the airway. Major clefts must be surgically repaired, either by a
lateral approach or laryngofissure.
Trachea
Tracheal Agenesis
This is a rare anomaly characterized by extreme respiratory distress, inability to vocalize,
and inability to intubate. Survival is rare and correction essentially impossible.
Malformations seen with this anomaly form patterns which overlap with, but are distinct
from, the VACTERL association.
Tracheomalacia
Primary tracheomalacia is an extremely rare entity resulting from a congenital deformity
of the supporting tracheal rings. Patients usually experience expiratory stridor and
varying degrees of respiratory distress, based on the extent of the lesion. Flexible
bronchoscopy may be used to visualize the trachea during respiration in the awake
patient. Commonly, collapse of the anterior tracheal wall against the soft posterior
component is seen. Intervention is usually unnecessary because most cases are self-
limited, but in severe cases it may be necessary to place a tracheotomy as a stent for the
trachea during development.
Secondary tracheomalacia usually results from extrinsic compression, as in vascular
anomalies, or secondary to surgical intervention, as in tracheoesophageal fistula repair.
Symptoms may be similar to those in primary tracheomalacia, with audible expiratory
stridor and occasional wheezing. Some patients present with reflex apnea and recurrent
pneumonitis. Therapy should be directed toward the underlying lesion in cases of
vascular compression, whereas those cases that are secondary to surgical intervention
usually require only careful observation and the necessary wait for growth and
development.
Tracheoesophageal Fistula
This anomaly may occur in various forms (Fig. 83.7). The most common variety involves
proximal esophageal atresia with the distal esophagus communicating with the trachea. A
less common and more subtle form is the H variety, in which a small communication
exists between the upper trachea and the upper third of the esophagus. Other rare variants
also may be seen.

FIGURE 83.7. Tracheoesophageal fistula is most
commonly associated with esophageal atresia. About
85% of patients with esophageal atresia have an
associated distal tracheoesophageal fistula. Ten percent
present with isolated esophageal atresia, whereas about
4% present with isolated tracheoesophageal fistula.
Esophageal atresia with a proximal tracheoesophageal
fistula occurs in 0.5% of patients, whereas 0.5%
demonstrate esophageal atresia with a double tracheoesophageal fistula.



Patients with esophageal atresia present with immediate feeding difficulties and
aspiration soon after birth. This situation should alert the consultant to the possibility of
the diagnosis, which can be confirmed by passing a small feeding tube into the
hypopharynx. Obviously the tube will not pass farther and will curl up in the pharynx.
This will present the classic radiologic finding of a curled tube in the pharynx and an air
bubble in the stomach. The more subtle H fistulae require careful observation by the
radiologist during fluoroscopy. In these cases, however, endoscopy remains the mainstay
of diagnosis. A small depression should be noted at some point on the posterior trachea,
which may be carefully cannulated by the endoscopist (Fig. 83.8). Management involves
surgical correction in all cases.

FIGURE 83.8. A tracheoesophageal fistula demonstrated
on the posterior tracheal wall, which has been cannulated
with a small catheter by the endoscopist (arrow). This
provides confirmation that the lesion communicates with
the esophagus.



Vascular Anomalies
Because of the intimate relationship between the esophagus, trachea, and great vessels
during embryologic development, the potential for malformation is ever present. Vascular
anomalies may either completely encircle the esophagus and trachea, thereby producing
obstruction, or compress the anterior wall of the trachea alone. Magnetic resonance
imaging seems to be useful in identifying these anomalies.
Anomalous Subclavian Artery
An aberrant right subclavian artery sometimes arises from the left descending aorta,
passes behind the esophagus and trachea, and then follows its normal course on the right
side. This produces a compression of the esophagus that is seen as a pulsatile lesion on
the posterior wall. A barium esophagogram demonstrates a compression passing
obliquely up and to the right on the AP view.
Double Aortic Arch
The so-called complete vascular ring encircles the esophagus and trachea in this lesion
(Fig. 83.9). There are essentially two forms of this anomaly: either the anterior arch is
larger than the posterior, or vice versa. Management consists of division of one
component.

FIGURE 83.9. Double aortic arch, showing the anterior
and posterior components that compress both the
esophagus and trachea.



Right Aortic Arch
A complete ring may be formed by a right aortic arch and a persistent ligamentum
arteriosum or ductus arteriosus (Fig. 83.10). These latter two structures may pass behind
the esophagus to reach the aorta on the right side. This can give rise to a situation similar
to the double aortic arch in which the trachea and esophagus are compressed.

FIGURE 83.10. A right aortic arch (RA) with a persistent
ligamentum arteriosum. The ligamentum passes behind
the esophagus to reach the aorta on the right side. This
leads to compression of both the trachea and the
esophagus.



Innominate Artery Compression
The innominate artery may arise more to the midline than usual in some patients, causing
anterior compression of the trachea (Fig. 83.11). These patients have a normal barium
esophagogram because there is no impingement on the esophagus. A persistent
impingement on the anterior tracheal wall at the thoracic inlet may be seen on a lateral
chest radiograph. The diagnosis is usually suspected in patients with apnea episodes,
recurrent pneumonitis, or expiratory stridor. Endoscopic confirmation is usually
necessary. In severe cases an aortopexy is undertaken and the aortic arch suspended from
the anterior sternum.

FIGURE 83.11. The innominate artery may arise more to
the midline than usual, causing anterior compression of
the trachea. In severe cases, this may be a clinically
significant anomaly.



Tracheal Stenosis
Most cases of congenital tracheal stenosis are secondary to complete tracheal rings. One
or more rings may extend over the entire length of the trachea. Management should be
conservative if possible, including aggressive medical therapy for upper respiratory
infections (corticosteroids and antibiotics). In more severe cases, surgical intervention
may be necessary, with either resection of the stenotic segment and end-to-end
anastomosis or a costal cartilage implant running the full length of the trachea on the
anterior wall. The latter should be reserved for cases involving all tracheal rings. Surgical
intervention in small infants should probably be undertaken using cardiopulmonary
bypass, which facilitates the procedure and reduces operating time.
Esophagus
Duplication
Most esophageal duplications occur as foregut cysts in the superior or posterior
mediastinum or as true duplications in or along the lower third of the esophagus. Because
the mucosa of these structures often contains acid-secreting cells, bleeding and ulceration
can occur.
Most patients present with respiratory complaints, including stridor and cough.
Radiologic studies, including plain films and fluoroscopy, are usually diagnostic. There is
a high incidence of vertebral anomalies with this lesion; thus, studies of the thoracic
cervical spine should be performed as part of the evaluation if the plain films of the chest
are positive. Treatment is directed toward surgical removal.
Hiatal Hernia
Congenital esophageal hiatal hernia is a rare anomaly. In more severe cases, significant
pulmonary involvement places the neonate at serious risk. Surgical repair is indicated,
and there is strong evidence that placing the newborn on the extracorporeal membrane
oxygenator may improve long-term survival.
Patients with less severe involvement may present with symptoms of gastroesophageal
reflux. There is growing evidence that this problem may initiate a multitude of respiratory
symptoms, such as stridor, apnea, and recurrent pneumonitis as the child develops.

HIGHLIGHTS
The otolaryngologist must thoroughly understand the
developmental anatomy of the upper aerodigestive tract to
properly comprehend developmental anomalies in this region.
The pediatric and adult larynx differ in many respects,
including location, configuration, and consistency. This makes
this structure susceptible to disease processes not seen in the
adult.
Stridor, respiratory distress, and feeding difficulties are often
the presenting features of upper aerodigestive tract anomalies.
These signs and symptoms differ depending on the anatomic
location.
The physical examination, including the patient's position and
color, may be significant in localizing the anomaly.
The use of diagnostic imaging techniques, including
fluoroscopy, contrast esophagogram, and CT scan, are often
useful in differentiating various anomalies. The role of
magnetic resonance imaging and ultrasonography continues to
evolve.
Endoscopic evaluation with both flexible and rigid instruments
remains the mainstay of diagnosis.
Choanal atresia appears to be the most common nasal anomaly
causing respiratory distress. It may be bony or membranous.
Surgical correction may be performed endoscopically in
selected cases.
The larynx appears to be the anatomic structure most
commonly affected by developmental anomalies in the upper
aerodigestive tract. Lesions such as congenital laryngeal stridor,
webs, and congenital stenosis appear to be the most common
lesions. Neurogenic lesions and developmental cysts also may
be noted.
The tracheobronchial tree is less often affected. The most
common lesions are congenital stenosis, tracheomalacia, and
various vascular anomalies causing extrinsic compression.
The esophagus is sometimes involved in congenital anomalies
of the aerodigestive tract, including esophageal atresia with
associated tracheoesophageal fistula, as well as duplication
anomalies and hiatal hernia. Gastroesophageal reflux may play
a role in many acquired anomalies of the airway in the older
child.
SUGGESTED READING
Altman KW, Wetmore RF, Marsh RR. Congenital airway abnormalities requiring tracheotomy: a profile of
56 patients and their diagnoses over a 9 year period. Int J Pediatr Otorhinolaryngol 1997;41:199.
Benjamin B. Endoscopy in esophageal atresia and tracheoesophageal fistula. Ann Otol Rhinol Laryngol
1981;90:376.
Benjamin B. Tracheaomalacia in infants and children. Ann Otol Rhinol Laryngol 1984;93:438.
Cotton RT, Richardson M. Congenital laryngeal anomalies. Otolaryngol Clin North Am 1981;14:203.
Evans JA, Greenberg CR, Erdile L. Tracheal agenesis revisited: analysis of associated anomalies. Am J
Med Genet 1999;82:415.
Fearon B, Whalen JS. Tracheal dimensions in the living infant. Ann Otol Rhinol Laryngol 1967;76:964.
Healy GB, McGill T, Friedman EM. Carbon dioxide laser in subglottic hemangioma. Ann Otol Rhinol
Laryngol 1984;93:370.
Healy GB, McGill TJ. Laryngo-tracheal problems in the pediatric patient. Springfield, IL: Charles C
Thomas, 1979.
Katz M, Konen E, Rozenman J, et al. Spiral CT and 3D image reconstruction of vascular rings and
associated tracheobronchial anomalies. J Comp Assist Tomogr 1995;19:564.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

84 NEONATAL RESPIRATORY DISTRESS
Head & Neck SurgeryOtolaryngology
84




NEONATAL RESPIRATORY DISTRESS
CHARLES M. MYER III
JAMES H. LIU

C.M. Myer III and J.H. Liu: Department of Pediatric Otolaryngology Head and Neck Surgery,
Children's Hospital Medical Center, Cincinnati, Ohio.


Nose
Evaluation and Management
Oropharynx/Hypopharynx
Evaluation and Management
Larynx
Evaluation and Management
Trachea/Bronchi
Evaluation and Management
Stridor in the Neonate
Chapter References
The signs and symptoms of obstruction in the neonate are characteristic of the site: nasal,
oropharyngeal, supraglottic, glottic, subglottic, or tracheobronchial. Regardless of the
cause of the obstruction, respiratory distress produces hypoventilation with an increase in
partial pressure of carbon dioxide (Pco
2
) and decrease in partial pressure of oxygen (Po
2
).
As with other conditions, the potential causes of neonatal respiratory distress can be
categorized as congenital, traumatic, iatrogenic, inflammatory, and neoplastic (1,2,3,4,5
and 6).
NOSE
Evaluation and Management
Because infants are initially obligate nasal breathers, nasal obstruction frequently causes
severe respiratory distress in this group of neonates. Although patients generally have no
stridor with nasal obstruction, there is often a snorting type of respiration with nasal
flaring. Cyanotic episodes are frequent but may be interrupted during episodes of crying,
a phenomenon known as cyclical cyanosis. Chest retractions are common in this age
group because of the severity of the obstruction. Feeding may be difficult because
patients are required to breathe through their mouths at the same time they are feeding.
In some cases, there may be external nasal abnormalities that allow the diagnosis to be
made readily. Small pits or dimples along the midline of the nose suggest a nasal
dermoid. These may be found from the nasal dorsum to the columella. Similarly, a
midline nasal mass may represent an encephalocele, glioma, dermoid, or even extension
of an intracranial vascular anomaly. Craniofacial anomalies, including Treacher Collins
syndrome and Apert syndrome, may present with nasal obstruction, and recognition of
one of these anomalies should direct the examination to the nose and nasopharynx.
After the external assessment, a thorough intranasal examination should be undertaken.
Anterior nasal stenosis is uncommon, but obstruction at the level of the piriform aperture
secondary to medial overgrowth of the maxilla may cause distress. This is especially
prominent if there is associated turbinate hypertrophy. Examination of the intranasal
structures with a flexible nasopharyngoscope or rigid telescope can identify the cause of
obstruction. The inferior meatus should be examined carefully for nasolacrimal duct cysts
(Fig. 84.1). Passing the nasopharyngoscope into the posterior nostril allows examination
of the posterior choana and nasopharynx. If choanal atresia is suspected because of the
inability to pass a small feeding catheter (e.g., no. 5 or 6 French) or the
nasopharyngoscope, radiographic evaluation is appropriate (Fig. 84.2). Children with
either piriform aperture stenosis or choanal atresia should be assessed by a geneticist
because of the high incidence of concomitant developmental anomalies. Adenoid
hypertrophy or a nasopharyngeal tumor also may be identified as the cause of obstruction
if the posterior choana is patent.

FIGURE 84.1. A nasolacrimal duct cyst may be
identified under the inferior turbinate and may cause
nasal obstruction. Such children often present with
concomitant dacryocystitis.



FIGURE 84.2. Choanal atresia may be identified
endoscopically (A) and confirmed by computed
tomography scan (B).



Radiographic evaluation of patients with nasal obstruction may be necessary. A
computed tomographic (CT) scan provides bony and soft-tissue detail. In some
conditions, including a midline nasal mass that may have an intracranial connection,
magnetic resonance imaging (MRI) may be the better study. Consultation with a pediatric
neuroradiologist is recommended to optimize care.
Regardless of the cause of obstruction, establishing a secure airway is paramount. In
many circumstances, this must be done before any investigative procedures. If the child
has no underlying lung disease or laryngotracheal abnormalities, placement of an oral
airway may be sufficient. An alternative to the conventional oral airway may be a feeding
nipple cut at the end. Either of these should be secured by taping or tracheotomy ties
placed around the head. Oxygen saturation monitoring can determine the efficacy of this
maneuver and, if the child does not maintain adequate saturation levels, supplemental
oxygen may be required. Alternatively, orotracheal intubation with possible ventilatory
support may be required. In any child with airway obstruction, failure to maintain
adequate ventilation with an endotracheal tube in place may signify intrinsic pulmonary
disease, and the active assistance of a neonatologist should be obtained.
OROPHARYNX/HYPOPHARYNX
Evaluation and Management
After the possibility of nasal obstruction has been eliminated, examination of the
oropharynx and hypopharynx is appropriate. Patients with obstruction in this area usually
present with inspiratory stridor that is coarse and increases during sleep. The cry is
usually normal, but it may be muffled. Sternal and intercostal retractions are common and
may increase to total chest retractions with severe obstruction. Feeding may be difficult
or impossible because there is anatomic obstruction. Stridor is frequently worse with
supine positioning, feeding, and agitation. If immediate intervention is needed, placement
of an oral airway or endotracheal tube must be considered.
The presence of macroglossia, glossoptosis, or neoplastic disorders should be ascertained
during examination of the oral cavity and oropharynx. A flexible endoscopic examination
performed through the mouth or nose may demonstrate a mass in the vallecula, including
lingual thyroid, dermoid, or vallecular cyst. Hemangioma, lymphangioma, or other
vascular malformations may be identified.
Depending on the anatomic abnormality identified, a CT or MRI scan may be appropriate
for further assessment of the airway. If no obvious abnormality can be identified from the
examination but the child demonstrates evidence of airway obstruction at the
oropharyngeal or hypopharyngeal level, a videofluoroscopic examination to observe
dynamic changes of the airway may allow a diagnosis to be rendered. Glossoptosis,
lateral pharyngeal wall collapse, or laryngomalacia, a supraglottic cause of airway
obstruction, may be identified on this radiographic study. The use of pulse oximetry is
important in the ongoing assessment of the severity of airway obstruction at any level of
the airway.
If there is severe respiratory distress in patients with oropharyngeal or hypopharyngeal
obstruction, airway support is appropriate. In some cases, use of a nasopharyngeal airway
may be all that is required. When hypopharyngeal collapse is present, the use of nasal
continuous positive airway pressure may relieve symptoms. Alternatively, an oral airway
may bypass the level of obstruction. In children with severe glossoptosis and retrognathia
(i.e., Pierre Robin sequence), prone positioning may be beneficial. Pulse oximetry
monitoring in a serial fashion may be required during the first several months for an
infant with Pierre Robin sequence because some of these children tend to develop
progressive airway obstruction. Even if the child is relatively asymptomatic, intubation
may be problematic because of the micrognathia and glossoptosis. Rigid bronchoscopy
may be necessary for airway control and, in some circumstances, a tracheotomy with
spontaneous mask ventilation may be needed.
The tongue-lip adhesion or a nasopharyngeal airway has been advocated as an alternative
to tracheotomy in children with severe airway obstruction and Pierre Robin sequence. We
favor a tracheotomy in these patients. If the child has a cleft palate associated with the
Pierre Robin sequence, the tracheotomy is not removed until the cleft palate is repaired. If
there is no cleft palate, the airway obstruction frequently resolves after a few months and
the tracheotomy can be removed.
LARYNX
Evaluation and Management
Like neonates with oropharyngeal or hypopharyngeal obstruction, children with
supraglottic laryngeal obstruction often present with a muffled cry. They frequently
produce snorting respirations during sleep and coarse inspiratory sounds at rest. In severe
cases, suprasternal and intercostal retractions may be seen. Feeding may be difficult if
there is a mass lesion or severe obstruction.
The larynx is usually assessed by flexible laryngoscopy performed through the nose or
the mouth. Passage of the endoscope through the mouth may be easier, but nasal passage
of the endoscope seems to provide better stabilization of the endoscope and allows a
more thorough examination. Supine positioning, feeding, and agitation often exacerbate
the degree of obstruction. Dynamic and static processes can produce obstruction at this
level.
Although plain films may offer some assistance in the assessment of a mass lesion in this
area, a CT or MRI scan is almost always needed for a thorough assessment.
Videofluoroscopy may be important if laryngomalacia is suspected. In some patients, a
diagnosis cannot be determined via these investigative means (Fig. 84.3) and then
microlaryngoscopy, bronchoscopy, and esophagoscopy should be performed. Depending
on the pathologic condition encountered, direct surgical intervention, including
epiglottoplasty or cyst aspiration, may be appropriate. In other circumstances,
endotracheal intubation or tracheotomy are necessary before instituting definitive therapy
at a later date.

FIGURE 84.3. Laryngomalacia is demonstrated best by
flexible endoscopy, but it may be demonstrated
satisfactorily with rigid endoscopy.



Patients with glottic airway obstruction usually present with a hoarse cry but may be
aphonic. These patients usually have inspiratory stridor initially, which may become
expiratory if the obstruction increases. With severe obstruction, inspiratory and
expiratory stridor and chest retractions are common. Unlike patients with oropharyngeal,
hypopharyngeal, and supraglottic obstruction, patients with glottic obstruction generally
do not have difficulty with feeding because there is no physical obstruction in the
pharynx. If airway obstruction is severe, the inability to eat is caused by air hunger rather
than an anatomic blockage. In addition to nasal flaring, patients may demonstrate some
degree of chest retractions.
Evaluation of the glottic region should include flexible laryngoscopy and airway
radiographs. A high kilovoltage technique is beneficial because it highlights the airway in
comparison with the surrounding soft tissues. A flexible laryngoscopic examination is
essential in the evaluation of this region because vocal cord paralysis is a dynamic
process that cannot be determined when a patient is fully anesthetized. Although other
abnormalities may be diagnosed with a flexible examination, including webs, atresia,
neoplastic disorders, stenosis, and clefts, a rigid examination allows a more detailed and
complete assessment to be made (Fig. 84.4). Laryngeal atresia is uncommon and
incompatible with life. If it is identified, an emergent tracheotomy may be necessary;
however, some of these patients may have an associated laryngotracheoesophageal cleft
or a tracheoesophageal fistula that allows ventilation and oxygenation for a period of
time. In other patients with glottic obstruction, endotracheal intubation may be sufficient.

FIGURE 84.4. In this autopsy specimen, the larynx has
been sectioned in a superior to inferior manner (right to
left), demonstrating laryngeal atresia (right) and a
laryngotracheoesophageal cleft (left).



Another potential cause of airway obstruction at the glottic level is laryngospasm. This
may occur secondary to gastroesophageal reflux disease (GERD) and should be
considered when the cause of obstruction is obscure. Consultation with a pediatric
gastroenterologist may be appropriate before assessing the patient with a pH probe study,
barium esophagogram, gastric emptying scan, or esophagoscopy. Our current
recommendation is a dual pH probe study to assess GERD in the proximal versus distal
esophagus.
In neonates who demonstrate subglottic airway obstruction, the cry may be hoarse but
often is normal. Similar to patients with glottic obstruction, these infants present with
inspiratory stridor early in their course that becomes expiratory as the obstruction
increases. With severe obstruction, the stridor may be both inspiratory and expiratory.
Xiphoid retractions are seen early in the course of subglottic obstruction and, as the
obstruction increases, retractions may be seen in the intercostal, suprasternal, and
supraclavicular regions. Patients feed normally except if there is severe airway
obstruction. Alar flaring is common. A barking type of cough often is associated with
subglottic obstruction.
Flexible endoscopic examination of the airway often is unrevealing in patients with
subglottic obstruction. The optics of the fiberoptic laryngoscope do not allow optimal
examination of the subglottic airway, and the common anatomic problems seen in this
region, including stenosis, cysts, and hemangiomas, may be missed (Fig. 84.5). If the
child's symptoms cannot be explained fully on the basis of the flexible endoscopic
examination and radio graphs, microlaryngoscopy, bronchoscopy, and esophagoscopy are
necessary. If airway distress is severe, intervention with an endotracheal tube or a
tracheotomy may be necessary before definitive surgical repair is undertaken (7,8,9,10
and 11).

FIGURE 84.5. A subglottic hemangioma is
characteristically located in the posterior and lateral
portion of the larynx.



TRACHEA/BRONCHI
Evaluation and Management
Patients with tracheobronchial obstruction usually have a normal cry, their stridor is
characteristically expiratory, and there may be a component of wheezing. With severe
obstruction, the stridor may be inspiratory and expiratory. Retractions are uncommon
unless there is severe obstruction. Patients feed normally unless there is severe airway
obstruction causing air hunger or if the obstruction is caused by extrinsic pressure
compressing the esophagus and trachea. Nasal flaring is common and these patients may
have a cough described as brassy. The initial evaluation of patients with suspected
tracheobronchial lesions is radiographic. Anteroposterior and lateral chest radiographs are
obtained and a barium esophagogram may be useful. Many clinicians prefer a rigid
endoscopic examination before obtaining a contrast esophagogram.
Intrinsic abnormalities of the tracheobronchial tree are uncommon but include complete
tracheal rings, transesophageal fistula, or a tracheal hemangioma. If any fistulae are
observed along the posterior tracheal wall, an attempt at catheterization should be made
to demonstrate continuity with the esophagus. Most cases of neonatal tracheobronchial
obstruction are caused by vascular compression.
Endoscopic examination demonstrates the compressive nature of the anomaly and
dictates further investigative and therapeutic maneuvers (Fig. 84.6). Esophagoscopy may
confirm the compressive nature of the lesion or offer evidence of an alternative
pathology, such as esophageal atresia.

FIGURE 84.6. Vascular compression of the trachea,
although best differentiated by radiographic imaging, can
be diagnosed endoscopically. These views demonstrate
examples of innominate artery compression of the trachea
(left) and a right aortic arch (right).



Depending on the severity of the obstruction, immediate intervention may be necessary in
the form of intubation. After the airway is stable, the diagnosis of compressive lesions of
the trachea and esophagus can be made with either an MRI or spiral CT scan. Vascular
rings, innominate artery compression of the trachea, and mediastinal cysts and neoplasms
are identified readily by MRI and spiral CT (2,12,13 and 14).
Stridor in the Neonate
The history, time of onset, and identification of initiating factors are helpful in the search
for the cause of stridor in the neonate (Fig. 84.7). The effects of positioning, feeding, or
crying are diagnostic clues. A history of prematurity, difficult labor or delivery, or
intubation at birth may be contributory. Because the findings may be scant on the general
physical examination in the absence of an obvious mass lesion in the neck, oral cavity, or
oropharynx, documentation of the quality of stridor and its relationship to the phase of
respiration is essential. It is important to characterize a newborn's cry and the presence of
dysphagia, odynophagia, or a persistent cough. After completing the history and physical
examination, the airway should be examined radiographically. Anteroposterior and lateral
neck films (i.e., high kilovoltage) and chest films during inspiration and expiration can
document abnormalities. In selected patients, videofluoroscopy helps delineate the full
extent of luminal collapse and diaphragmatic excursion. A contrast esophagogram can be
useful in the diagnosis of tracheoesophageal fistulae, esophageal stenoses, and vascular
anomalies or rings that cause extrinsic compression. Further information may be provided
by CT or MRI scans or a pH probe study.

FIGURE 84.7. Algorithm for evaluation of stridor in
children. (From Lee KL, ed. Textbook of otolaryngology
and head and neck surgery. New York: Elsevier,
1989:662.)



Direct endoscopic examination of the airway may not be necessary if the diagnosis can be
obtained confidently by a combination of radiographic studies and flexible endoscopy;
however, if patients show a progression of symptoms marked by increasing stridor,
weight loss, or feeding difficulties, microlaryngoscopy, bronchoscopy, and
esophagoscopy are necessary for diagnostic and therapeutic reasons. An echocardiogram
and electrocardiogram may provide important information about the severity of distress
and possible cardiac strain. Routine use of pulse oximetry and selective use of arterial
blood gases further enhance the evaluation process. An evaluation for GERD will be
appropriate in selected patients. When aspiration is a problem, a functional endoscopic
evaluation of swallowing may be useful. After the diagnosis has been obtained, definitive
therapy may be instituted. If no lesion is identified during the evaluation process and the
patient's respiratory status deteriorates progressively, the physician should consider
pulmonary, cardiac, central nervous, gastrointestinal, and metabolic-nutritional causes.
If there is an upper airway abnormality, intubation should relieve the symptoms of
respiratory distress. If there is primary pulmonary pathology, however, the patient may
remain symptomatic with tachypnea, hypoxemia, and hypercarbia, often requiring
ventilatory assistance. After upper airway pathology has been eliminated as a cause of the
patient's respiratory distress, the neonatologist should assume primary management of the
patient (2).

HIGHLIGHTS
Recognition of the signs and symptoms of airway obstruction is
the first step in diagnosis and management.
Because neonates are obligate nasal breathers, nasal obstruction
may precipitate life-threatening hypoventilation.
Airway obstruction involving the oropharyngeal and
supraglottic regions is often associated with cyanosis and other
breathing problems during feeding.
For patients with Pierre Robin sequence and airway obstruction,
tracheotomy provides the safest and most effective form of
long-term management.
Patients with glottic airway obstruction usually present with a
hoarse cry and may be aphonic. Their stridor is usually present
during inspiration.
Differentiation of compressive obstruction of the tracheal
airway is accomplished most effectively using MRI or spiral
CT.
Subglottic airway obstruction usually is associated with xiphoid
retractions, alar flaring, and a barking cough.
Examination with a flexible fiberoptic laryngoscope is essential
in the evaluation of vocal cord paralysis. The optics preclude
effective evaluation of the subglottic space in many children.
The most common causes of tracheobronchial obstruction in
neonates are various forms of vascular anomalies. Other causes
include complete tracheal rings, tracheoesophageal fistulae, and
tracheal hemangioma.
Differentiating between upper airway obstruction and
abnormalities of the lung parenchyma is critical. Although
management of the former is usually possible with tracheotomy
or intubation, management of the latter may require mechanical
ventilation.
CHAPTER REFERENCES
1. Healy GB. Evaluation of stridor. In: Healy GB, ed. Common problems in pediatric
otolaryngology. Chicago: Mosby-Year Book, 1990:359365.
2. Myer CM III, Cotton RT. Airway obstruction. In: Myer CM III, Cotton RT. A practical approach
to pediatric otolaryngology. Chicago: Mosby-Year Book, 1988:169205.
3. Pransky SM. Evaluation of the compromised neonatal airway. Pediatr Clin North Am
1989;36:15711582.
4. Zalzal GH. Stridor and airway compromise. Pediatr Clin North Am 1989;36:13891402.
5. Gonzalez C, Reilly JS, Bluestone CD. Synchronous airway lesions in infancy. Ann Otol Rhinol
Laryngol 1987;96:7780.
6. Gray SD, Johnson DG. Head and neck malformations of the pediatric airway. Semin Pediatr Surg
1994;3:160168.
7. Hawkins DB. Flexible endoscopy of the pediatric airway. In: Healy GB, ed. Common problems in
pediatric otolaryngology. Chicago: Mosby-Year Book, 1990:431437.
8. McGill T. Congenital anomalies of the larynx. In: Healy GB, ed. Common problems in pediatric
otolaryngology. Chicago: Mosby-Year Book, 1990:447456.
9. Cotton RT. Laryngeal stenosis: current management. In: Healy GB, ed. Common problems in
pediatric otolaryngology. Chicago: Mosby-Year Book, 1990:359365.
10. Cotton RT. Pediatric laryngotracheal stenosis. J Pediatr Surg 1984;19:699704.
11. Zalzal GH, Anon JB, Cotton RT. Epiglottoplasty for the treatment of laryngomalacia. Am Otol
Rhinol Laryngol 1987;96:7276.
12. van Son JA, Julsrud PR, Hagler DJ, et al. Imaging strategies for vascular rings. Ann Thorac Surg
1994;57:604610.
13. Spitz L. Esophageal atresia and tracheoesophageal fistula in children. Curr Opin Pediatr
1993;5:347352.
14. Gustafson LM, Liu JH, Link DT, Strife JL, Cotton RT. Spiral CT versus MRI in neonatal airway
evaluation: a case report. Int J Pediatr Otorhinolaryngol 2000;52:197201.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

85 RECURRENT RESPIRATORY PAPILLOMATOSIS
Head & Neck SurgeryOtolaryngology
85




RECURRENT RESPIRATORY PAPILLOMATOSIS
CRAIG S. DERKAY

C.S. Derkay: Department of Otolaryngology, Children's Hospital of the King's Daughters, Norfolk,
Virginia.


Introduction
Etiology
Human Papillomavirus
Recurrent Respiratory Papillomatosis
Epidemiology
Transmission
Clinical Features
Patient Assessment
History
Physical Examination
Airway Endoscopy
Other Considerations
Surgical Management
Recurrent Respiratory Papillomatosis Surgery
Preoperative Planning
Operative Technique
Postoperative Care
Recurrent Respiratory Papillomatosis Staging
Adjuvant Treatment Modalities
Chapter References
In discussing recurrent respiratory papillomatosis (RRP) of the aerodigestive tract, it is
helpful to review our current knowledge regarding the etiology of the disease, including
some basic information on human papillomavirus (HPV), the histopathology of
respiratory papillomas, as well as the epidemiology of the disease and risk factors for its
transmission. This chapter will also address the common clinical features seen in children
with RRP, including the pertinent findings on history, physical examination, endoscopy,
and imaging studies. Surgical treatments, including the use of laser and nonlaser
technologies, also will be addressed. Additionally, potential nonsurgical adjuvant
therapies and their current indications for use will be discussed. Complications of the
disease itself as well as of its treatment will be covered. A staging system for following
patients with RRP will be presented along with other new horizons for research and
treatment of this frustrating entity.
INTRODUCTION
Recurrent respiratory papillomatosis is a disease of viral etiology, caused by HPV types 6
and 11, associated with exophytic lesions of the airway. Although it is a benign disease,
RRP has potentially morbid consequences due to its involvement of the airway and to the
risk of malignant conversion.
Recurrent respiratory papillomatosis is both the most common benign neoplasm of the
larynx among children and the second most frequent cause of childhood hoarseness (1).
The disease is often difficult to treat because of its tendency to recur and spread
throughout the respiratory tract. Although it most often involves the larynx, RRP may
involve the entire aerodigestive tract. The course of the disease is variable, with some
patients experiencing spontaneous remission and others suffering from aggressive
papillomatous growth, requiring multiple surgical procedures over many years.
In most pediatric series, RRP is diagnosed between 2 and 4 years of age with a delay in
diagnosis from the time of onset of symptoms averaging about 1 year (2). Seventy-five
percent of the children have been diagnosed before their fifth birthday (3). It is estimated
that 1,500 to 2,500 new cases of childhood-onset RRP occur in the United States each
year. The incidence among children in the United States is estimated at 4.3 per 100,000
children, translating into more than 15,000 surgical procedures at a total cost of more
than $100 million per year (4). Anecdotal observations suggest that most patients are first
born; have young, primigravid mothers; and come from families of low socioeconomic
status (4,5 and 6). The clinical course is unpredictable, with malignant transformation
possible in chronic invasive papillomatosis.
Recurrent respiratory papillomatosis may have its clinical onset during either childhood
or adulthood. Two distinct forms are generally recognized: a juvenile or aggressive form
and an adult or less aggressive form. The aggressive form, although most prevalent in
children, also can occur in adults. Children whose RRP was diagnosed at younger ages
(<3 years) have been found to be 3.6 times more likely to have more than four surgeries
per year and almost 2 times more likely to have two or more anatomic sites affected than
were children whose RRP was diagnosed at later ages (>3 years) (7).
ETIOLOGY
Human Papillomavirus
Human papillomavirus is a small DNA-containing, nonenveloped icosahedral (20-sided)
capsid virus with a double-stranded circular deoxyribonucleic acid 7,900 base pairs long.
The present understanding is that HPV establishes itself in the basal layer, where viral
DNA enters the cell and elaborates RNA to produce viral proteins. Until the 1990s, HPV
had been suspected but not confirmed as the causative agent in RRP. This uncertainty
developed from an inability to culture the virus in vitro, and from the failure to
demonstrate viral particles consistently in papilloma lesions using electron microscopy or
HPV antibodies. Today, with the use of viral probes, HPV DNA has been identified in
virtually every papilloma lesion studied. The most common types identified in the airway
are HPV 6 and HPV 11, the same types responsible for genital warts. Specific viral
subtypes may be correlated with disease severity and clinical course. Children infected
with HPV 11 appear to have a more obstructive airway course early in the disease and a
greater need for tracheotomy (8). At least 90 different types of HPV have been identified
and are designated by numbers (i.e., HPV 6). The closer the numbers, the more similar
the viral subtypes are in their clinical manifestations.
An association between cervical HPV infection in the mother and the incidence of RRP
has been well established. Viral DNA has been detected in areas of normal-appearing
mucosa adjacent to papilloma lesions, suggesting a possible explanation for the
recurrence of the disease following thorough surgical removal (9). Adult-onset
respiratory papillomas could reflect either activation of virus present since birth or an
infection acquired in adolescence or adult life.
The universality of HPV in the lower genital tract rivals that of any other sexually
transmitted disease in humans. It is estimated that at least 1 million cases of genital
papillomas occur per year in the United States (10). These most often manifest as
condylomata acuminata involving the cervix, vulva, or other anogenital sites in women or
the penis of male sexual partners of affected women. HPV has been noted to be present in
the genital tract of as many as 25% of all women of child-bearing age worldwide. The
incidence of HPV infections in sexually active young college women is high, with a
cumulative incidence of 43% over a 36-month period in a recent study (11). Clinically
apparent HPV infection has been noted in 1.5% to 5% of pregnant women in the United
States (12). As in RRP, HPV 6 and 11 are the most common subtypes identified in
cervical condylomata.
Recurrent Respiratory Papillomatosis
Histologically, RRP appears as pedunculated masses with fingerlike projections of
nonkeratinized stratified squamous epithelium supported by a core of highly vascularized
connective tissue stroma (Fig. 85.1; see also Color Plate 27 following p. 370). The basal
layer may be either normal or hyperplastic, and mitotic figures are generally limited to
this layer. Cellular differentiation appears to be abnormal, with altered expression and
production of keratins. The degree of atypia may be a sign of premalignant tendency.
RRP lesions occur most often at anatomic sites in which ciliated and squamous
epithelium are juxataposed (13). The most common sites for RRP are the limen vestibuli,
the nasopharyngeal surface of the soft palate, the midline of the laryngeal surface of the
epiglottis, the upper and lower margins of the ventricle, the undersurface of the vocal
folds, the carina, and at bronchial spurs (5). In tracheotomized patients, RRP is often
encountered at the stoma and in the mid-thoracic trachea, areas that might be considered
iatrogenic squamociliary junctions. Papilloma lesions may be sessile or pedunculated and
often occur in irregular exophytic clusters (Fig. 85.2; see also Color Plate 28 following p.
370). Typically, the lesions are pinkish to white in coloration. Iatrogenic implantation of
papilloma may be preventable by avoiding injury to nondiseased squamous or ciliated
epithelium adjacent to areas of frank papilloma. Ciliated epithelium undergoes squamous
metaplasia when exposed to repeated trauma and is replaced with nonciliated epithelium
that creates an iatragenic squamociliary junction. This may also explain the observation
that RRP flourishes in the present of uncontrolled gastroesophageal reflux (14).

FIGURE 85.1. Histologic section of papilloma,
demonstrating fingerlike projection of nonkeratinized
stratified squamous epithelium and vascularized
connective tissue stroma. (See also Color Plate 27
following p. 370.)



FIGURE 85.2. Sessile papilloma lesions involving the
true vocal folds. (See also Color Plate 28 following p.
370.)



EPIDEMIOLOGY
Recurrent respiratory papillomatosis may affect people of any age, with the youngest
patient identified at 1 day of age and the oldest at 84 years (4). Childhood-onset RRP
(arbitrarily defined as patients diagnosed at less than 12 years of age) is most often
diagnosed between 2 and 4 years of age. Adult RRP peaks between the ages of 20 and 40
and has a slight male predilection; distribution among boys and girls is approximately
equal, and there are no apparent differences in surgical frequencies by gender or ethnicity
(7). Childhood-onset RRP is more common and is more aggressive than its adult
counterpart. The national registry of children with RRP, composed of the clinical
practices at 22 pediatric otolaryngology sites, calculates a mean number of procedures at
19.7 per child, with an average of 4.4 procedures per year (7). Children diagnosed before
3 years of age were found to be 3.6 times more likely to require more than four surgical
procedures per year and 2.1 times more likely to have two or more anatomic sites
involved than those diagnosed after their fourth birthday (7). In a survey of practicing
otolaryngologists in the United States, half of the adults with RRP had required fewer
than five procedures over their lifetime compared with less than 25% of the children.
Approximately equal percentages of children and adults (17% children versus 19%
adults) had very aggressive RRP (defined as requiring more than 40 lifetime operations),
although adults had more years to accumulate these operations (4). True incidence and
prevalence of RRP are uncertain. In a Danish subpopulation incorporating 50% of the
population of that country, the incidence of laryngeal papillomatosis was 3.84 cases per
100,000 (15). The rate among children was 3.62 per 100,000, whereas adult-onset cases
occurred at a rate of 3.94 per 100,000. These figures are comparable with those found in
a recent U.S. survey, which estimated an incidence in the pediatric population of 4.3 per
100,000 children and 1.8 per 100,000 adults. This translates into roughly 2,300 new
pediatric cases per year in the United States (4).
TRANSMISSION
The precise mode of HPV transmission remains unclear. Several studies have
convincingly linked childhood-onset RRP to mothers with genital HPV infections,
whereas circumstantial evidence suggests that adult disease may be associated with oral-
genital contact. Retrospective and recent prospective studies have confirmed that HPV
may be passed by vertical transmission from mother to child (16,17 and 18). In addition,
Kashima et al. (5) found that childhood-onset RRP patients were more likely to be first
born and vaginally delivered than were control patients of similar age. The researchers
hypothesized that primigravid mothers are more likely to have a long second stage of
labor and that the prolonged exposure to the virus leads to a higher risk of infection in the
first-born child. They also suggested that newly acquired genital HPV lesions are more
likely to shed virus than long-standing lesions, thus explaining the higher incidence of
papilloma disease observed among the offspring of young mothers of low socioeconomic
status, the same group that is most likely to acquire sexually transmitted diseases such as
HPV. Despite the apparent close association between maternal condylomata and the
development of RRP, few children exposed to genital warts at birth actually develop
clinical symptoms (19,20). It is not well understood why RRP develops in so few
children whose mothers have condylomata. The most likely method of maternal-fetal
HPV transmission is through direct contact in the birth canal. This would explain the
clinical observation that most children in whom RRPs develop are delivered vaginally to
mothers with a history of genital condylomatas (19). Although HPV could be recovered
from the nasopharyngeal secretions of 30% of infants exposed to HPV in the birth canal
(20) the number of infants expected to manifest evidence of RRP is only a small fraction
of this. Clearly, other factors (patient immunity, timing length and volume of virus
exposure, and local trauma) must be important determinants of development of RRP.
Even though cesarean section would seem to reduce the risk of transmission of the
disease, this procedure is associated with a higher morbidity and mortality for the mother
and a much higher economic cost than elective vaginal delivery. Shah et al. (19)
estimated that the risk of a child contracting the disease from a mother who has an active
condylomatous lesion and delivers vaginally is only about 1 in 400. The characteristics
that differentiate this one child from the other 399 are elusive. In light of the uncertainty
surrounding intrapartum exposure, there is presently insufficient evidence to support
delivery by cesarean section in all pregnant women with condylomata (21). Reports of
neonatal papillomatosis suggest that, in at least some cases, development of the disease
may occur in utero. Because cesarean section still does not prevent the development of
papilloma disease in all cases, a better understanding of the risk factors associated with
RRP is needed before the efficacy of cesarean delivery in preventing papilloma disease
can be fully assessed.
CLINICAL FEATURES
Because the most common symptoms of RRP are related to airway obstruction, it is not
uncommon for children to be misdiagnosed initially as having asthma, croup, or chronic
bronchitis. The hallmark of RRP in children is the triad of relentlessly progressive
hoarseness, stridor, and respiratory distress. Although hoarseness in children tends to be
overlooked or at least accepted until it reaches a certain level of severity, any infant or
young child with symptoms of voice change, along with obstructive airway symptoms or
recurrent croup, warrants laryngoscopy to rule out neoplasia, with RRP being the most
likely lesion.
Children with RRP most often present with some degree of dysphonia. Unfortunately,
particularly in young children, changes in voice may go unnoticed. Stridor is often the
second clinical symptom to develop, beginning as an inspiratory noise and becoming
biphasic with progression of the disease. Less commonly, chronic cough, recurrent
pneumonia, failure to thrive, dyspnea, dysphagia, and acute life-threatening events may
be the presenting symptoms. The duration of symptoms prior to diagnosis varies. Not
uncommonly, a mistaken diagnosis of asthma, croup, allergies, vocal nodules, or
bronchitis is entertained before a definitive diagnosis is made.
Because of the rarity of RRP and the slowly progressive nature of the disease, some cases
may go unrecognized until respiratory distress results from papillomas obstructing the
airway. The result is a relatively high need for tracheotomy to be performed in these
children. Shapiro et al. noted that RRP tracheotomy patients presented at a younger age
and with more widespread disease, often involving the distal airway prior to tracheotomy
(22). In their experience with 13 patients, they did not feel that the tracheotomy itself led
to spread of disease outside the larynx. In the Centers for Disease Control and Prevention
(CDC) registry, children with tracheotomy were initially diagnosed with RRP at a
younger age (2.7 years) than those without a tracheotomy (3.9 years) (7). Others have
suggested that tracheotomy may activate or spread disease lower in the respiratory tract.
Cole et al. (23) reported that tracheal papillomas developed in half of their tracheotomy
patients and that, despite attempts to avoid this procedure, 21% of their patients still
required a long-term tracheotomy. Prolonged tracheotomy, and the presence of subglottic
papilloma at the time of tracheotomy, have been associated with an increased risk of
distal tracheal spread. Most researchers agree that tracheotomy is a procedure to be
avoided unless absolutely necessary. When a tracheotomy is unavoidable, decannulation
should be considered as soon as the disease is managed effectively with endoscopic
techniques. Children with bronchopulmonary dysplasia who require prolonged
endotracheal intubation also may be at increased risk for development of RRP. Through
interruption of the continuous respiratory mucosal surface, an endotracheal tube may
have the same role in the mechanical dissemination/implantation of RRP as does
tracheotomy. Gastroesophageal reflux disease also has been identified as a potential risk
factor for disease persistence, although additional research is necessary to verify this
anecdotal observation.
Extralaryngeal spread of respiratory papillomas has been identified in approximately 30%
of children and in 16% of adults with RRP. The most frequent sites of extralaryngeal
spread were, in order of frequency, the oral cavity, trachea, and bronchi (4). A possible
link between RRP and immunodeficiency states also has been observed. Both children
and adults with the acquired immunodeficiency syndrome or congenital
immunodeficiencies or those on immune suppression after organ transplantation have
been identified with RRP (4). Malignant transformation of RRP into squamous cell
carcinoma has been documented in several case reports. A total of 26 patients was
identified as having progressed to squamous cell carcinoma in the Task Force survey (4).
When death occurs, it is usually associated with a complication of frequent surgical
procedures or caused by respiratory failure due to distal disease progression. RRP
presenting in the neonatal period is thought to be a negative prognostic factor with a
greater likelihood for mortality and need for tracheotomy.
PATIENT ASSESSMENT
History
Persistent or progressive stridor and dysphonia, with the possible development of
respiratory distress, are the most consistent signs and symptoms of RRP in children. In
the absence of severe respiratory distress, a careful history should be obtained.
Information regarding the time of onset of symptoms, possible airway trauma including a
history of previous intubation, and characteristics of the cry are obviously important.
Hoarseness, although a common and often benign clinical complaint in young children,
always indicates some abnormality of structure or function. Because of the precision of
laryngeal mechanics, hoarseness may result from a remarkably small lesion and thus be
an early sign in the course of a disease process. On the other hand, if the lesion's origin is
remote from the vocal cords, hoarseness may present as a late sign. Although
histologically the same lesion, a papilloma that produces hoarseness in one patient may
produce stridor and obstruction in another, depending on the size and location of the
lesion. The quality of the voice change may give only limited clues to its etiology,
whereas other characteristics such as age of onset, rate of progression, associated
infection, history of trauma or surgery, and the presence of respiratory or cardiac distress
may be of much greater significance. A low-pitched, coarse, fluttering voice suggests a
subglottic lesion, whereas a high-pitched, cracking voice, aphonia, or a breathy voice
suggests a glottic lesion. Associated high-pitched stridor also suggests a glottic or
subglottic lesion. Although stridor that has been present since birth is more often
associated with laryngomalacia, subglottic stenosis, vocal cord paralysis, or a vascular
ring, it should be realized that neonates also can present with papillomatosis. Associated
symptoms such as feeding difficulties, allergic symptoms, vocal abuse, and the presence
of hereditary congenital anomalies may help distinguish RRP from alternative diagnoses,
including vocal fold nodules, vocal fold paralysis, subglottic cysts, subglottic
hemangioma, and subglottic stenosis. In the absence of any history suggesting these
lesions, review of the perinatal period may reveal a history of maternal or paternal
condylomata. If the onset of stridor and dysphonia is gradual and progressive over weeks
or months, then neoplastic growth compromising the airway must be considered and
investigated.
Certainly not every child with a hoarse voice or cry merits investigation beyond an
assessment of the symptom. However, in the presence of hoarseness with respiratory
distress, tachypnea, decreased air entry, tachycardia, cyanosis dysphagia, chronic cough,
failure to thrive, recurrent pneumonia, or dysphagia, the larynx must be visualized and a
firm diagnosis of the cause of hoarseness must be made. Any child with slowly
progressive hoarseness merits investigation and the clinician should not wait until total
aphonia or airway problems occur.
Physical Examination
Children presenting with symptoms consistent with RRP must undergo a thorough and
organized physical examination. The child's respiratory rate and degree of distress must
first be assessed. The physician should observe the child for tachypnea or the onset of
fatigue that may indicate impending respiratory collapse. The child should be observed
for flaring of the nasal ala and the use of accessory neck or chest muscles. Increasing
cyanosis and air hunger may cause the child to sit with the neck hyperextended in an
attempt to improve airflow. If a child is gravely ill, additional examination should not be
undertaken outside the operating room (OR), the emergency room, or the intensive care
unit, where resuscitation equipment for intubation of the airway, endoscopic evaluation,
and possible tracheotomy are readily available. In the stable, well-oxygenated child,
additional examination can proceed. The most important part of the examination is
auscultation with the aid of a stethoscope. The physician should listen over the nose, open
mouth, neck, and chest to help localize the probable site of the respiratory obstruction.
The researchers prefer to pull the bell off the stethoscope and listen over these areas with
the open tube. The respiratory cycle, which is normally composed of a shorter inspiratory
phase and a longer expiratory phase, should then be observed. Stridor of a laryngeal
origin is most often musical and may begin as inspiratory, but will progress to biphasic
with worsening airway narrowing. Infants with stridor should be placed in various
positions to elicit any changes in the stridor. A child with RRP would not be expected to
demonstrate much change in the stridor with position change in contrast to infants with
laryngomalacia, a vascular ring, or a mediastinal mass. Pulse oximetry can add an
accurate quantitative analysis of the child's respiratory state. In the stable patient in whom
asthma is a likely diagnosis, pulmonary function testing combined with arterial blood gas
evaluation also may be helpful.
Airway Endoscopy
The preoperative diagnosis of RRP is best made with a flexible fiberoptic
nasopharyngoscope. Careful, sequential inspection of the pharynx, hypopharynx, larynx,
and subglottis provides the critical information necessary to make the diagnosis of RRP
and allows estimation of lumen size, vocal cord mobility, and the urgency of operative
intervention. Advances in instrumentation of flexible nasopharyngoscopes have resulted
in instruments as small as 1.9 mm in diameter that allow passage in even the smallest
newborns. Even the smallest diameter scopes provide images that can be seen on a video
monitor and recorded for later review. Topical decongestion and local anesthesia can be
applied by spray, dropper, or pledget. Oxymetazoline is the decongestant of choice
because of its lack of cardiac side effects. Either topical tetracaine or lidocaine may be
used to enhance patient cooperation, but the dosage must be critically monitored in the
small infant to avoid cardiotoxicity.
Most clinicians find that visualization with the flexible nasopharyngoscope is far superior
to that obtained with indirect mirror laryngoscopy in young children. Patient cooperation,
however, is required even with good topical anesthesia. In infants, this is not a large issue
because they can easily be restrained in a sitting-up position in the parent's or nurse's lap
for evaluation. Likewise, most children over 6 or 7 years of age can be talked into
cooperating for the examination. It is the intermediate age group, between 1 and 6 years
of age, who may be the most difficult to examine, taxing the patience and skill of even
the most experienced clinicians. Although dynamic evaluation may be appreciated when
children are spontaneously breathing, endoscopy in the OR under anesthesia is warranted
in any child suspected to have RRP who cannot be fully examined in the outpatient
setting.
Other Considerations
Children newly diagnosed with RRP warrant a substantial time commitment on the part
of the otolaryngologist to engage the family in a frank and open discussion of the disease
and its management. Support groups such as the Recurrent Respiratory Papilloma
Foundation (phone: 609-530-1443) can be a vital resource for information and support.
RRP patients require frequent office visits and endoscopic procedures at the outset to
establish the aggressiveness of their disease. They are encouraged to return to the office
or call as often as necessary while family members and the health care team become
familiar with the child's symptoms and level of distress. Although infant home intercom-
type monitors are often recommended, apnea/bradycardia monitors and pulse oximetry
are generally not necessary. Repeat flexible fiberoptic laryngoscopy may be used in the
office setting, as may speech and language therapy if offered early in the course of the
disease. Control of other medical factors such as reflux and asthma is also aggressively
pursued.
Surgical Management
No single modality has consistently been shown to be effective in eradication of RRP.
The current standard of care is surgical therapy with a goal of complete removal of
papillomas and preservation of normal structures. In patients in whom anterior or
posterior commissure disease or highly aggressive papillomas are present, the goal may
be subtotal removal with clearing of the airway. It is advisable to debulk as much disease
as possible while preserving normal morphology and anatomy and preventing the
complications of subglottic and glottic stenosis, web formation, and a diminished airway.
The CO
2
laser has been favored over cold instruments in the treatment of RRP involving
the larynx, pharynx, upper trachea, and nasal and oral cavities (4). When coupled to an
operating microscope, the laser vaporizes the lesions with precision, causing minimal
bleeding. When used with a no-touch technique, it minimizes damage to the vocal cords
and limits scarring. The CO
2
laser has an emission wave length of 10,600 nm and
converts light to thermal energy. It provides a controlled destruction of tissues with
vaporization of water. It also cauterizes tissue surfaces. The smoke plume contains water
vapor and destroyed tissue material. Although the CO
2
laser allows for precision of
surgery and excellent hemostasis, multiple procedures are often necessary. Frequent
interval laser laryngoscopies are recommended in an attempt to avoid tracheotomy and
permit the child to develop good phonation with preservation of normal vocal cord
anatomy. The newest generation of laser microspot micromanipulator enables the
surgeon to use a spot size of 250 mm at 400-mm focal length and 160 mm at 250-mm
focal length. The 710 Accuspot Sharplan laser is our current choice for managing RRP of
the larynx. This unit allows direct visualization of the surgical target with elimination of
the parallax problem inherent in earlier models. I use the Accuspot in the defocused mode
to debulk papilloma initially and then focus the 250-mm spot size to excise papillomas
from potentially tricky areas such as near the anterior and/or posterior commissure and
along the true vocal cords. Although the CO
2
laser is the most commonly used laser for
RRP in the larynx, the KTP, as well as the Argon laser, could also be used (Table 85.1).

TABLE 85.1. POTENTIAL SURGICAL
MODALITIES FOR RRP



The use of the CO
2
laser on the true vocal folds must be judicious given the potential for
significant postoperative scar tissue formation from unrecognized heat transfer. To
minimize the risk of scar formation in the true vocal folds, cold steel excision can be used
successfully using the principles of phonomicrosurgery, submucosal infusion, and
microinstrumentation. This approach may have treatment advantages over CO
2
laser
surgery, especially in the adult RRP patient (24,25). In their initial series, Zeitels and
Sataloff report recurrence of papilloma in 0 of 6 adults who underwent resection for
primary disease at 2 years follow-up. Of those who presented with recurrent
papillomatosis, 6 of 16 (38%) continued to recur after their microflap procedure (25).
Recent publications have highlighted the potential benefits of newer surgical technologies
in managing RRP. Bower et al. evaluated the feasibility and safety of the flash pump dye
laser in nine children and found good early results (26). McMillan et al. have published
preliminary results regarding their positive experience with the 585-nm pulsed dye laser
in three patients (27). Bergler et al. reported on the successful use of argon plasma
coagulation to treat a 3-year-old with recalcitrant RRP (28). A number of investigators
are now complementing and in some cases replacing their use of the CO
2
laser with the
endoscopic microdebrider as means of quickly debulking laryngeal disease (29).
Although this technique is relatively new, with the development of smaller (< mm)
shaver blades, it may offer the patient some benefits in terms of reduced laryngeal
scarring in relation to the CO
2
laser.
Because there is currently no therapeutic regimen that reliably eradicates HPV, when
there is a question about whether papilloma in an area needs to be removed, it is prudent
to accept some residual papilloma rather than risking damage to normal tissue and
producing excessive scarring. Even with the removal of all clinically evident papilloma,
latent virus may remain in adjacent tissue, which may explain the recurrent nature of
RRP. Therefore, the aim of therapy in extensive disease should be to reduce the tumor
burden, decrease the spread of disease, create a safe and patent airway, improve voice
quality, and increase the time interval between surgical procedures. Staged papilloma
removal for disease in the anterior commissure is appropriate to prevent the apposition of
two raw mucosal surfaces. The surgeon who is not aware of injury to deeper tissue layers
with injudicious laser usage may encounter unacceptable scarring and subsequent
abnormal vocal fold function. Inappropriate and aggressive use of the laser also may
cause injury to nonaffected tissues and create an environment suitable for implantation of
viral particles. Use of the CO
2
laser also can result in delayed local tissue damage, which
may be related to the total number of laser surgeries and the severity of RRP disease.
Recurrent Respiratory Papillomatosis Surgery
I will briefly describe our current procedure for managing papilloma disease in the larynx
with the CO
2
laser. This technique is modified depending on the location of the disease,
the amount of previous laryngeal surgery, and the degree of airway obstruction. In some
circumstances, we prefer the use of the microdebrider, in others the KTP laser via the
ventilating bronchoscope, and in still others jet ventilation or insufflation anesthesia
techniques.
Preoperative Planning
Before the child enters the operating suite, the surgeon, anesthesiologist, and OR team
must select the proper size endotracheal tubes, laryngoscopes, and bronchoscopes and
ascertain that all ancillary equipment, including telescopes, light cords, suction tips, and
forceps are available and properly functioning. The surgeon, along with the OR team,
should check that all equipment used for the procedureincluding the surgical
microscope with appropriate size lens, the laser unit, the micromanipulator, filtered
suction, and smoke evacuation unitsare all properly functioning. In our institution, the
surgeon personally checks the laser for beam alignment by test-firing it prior to the child
entering the room. Laser safety is carefully monitored in our institution by the laser safety
committee. This includes a laser safety officer, a physician for each specialty that uses the
laser, nurses from the OR, a hospital administrator and biomedical engineer. All OR
personnel are required to wear eye protection whenever working around the laser.
Specially designed laser masks are required to be worn by OR personnel during the
surgery to prevent the inhalation of viral particles liberated during the laser procedure.
Before the institution of any anesthesia, the surgeon should discuss the pathology with
the anesthesiologist. Additionally, the staff within the OR also should be informed of the
surgeon's concerns so that appropriate instrumentation is ready. Intraoperative teamwork
is enhanced with the availability of video monitors during the operation because this
allows the entire OR staff to follow the operation as it progresses. Dialogue between the
surgeon and the anesthesiologist continues throughout the procedure regarding the
current status of ventilation, the amount of bleeding encountered, the motion of the vocal
cords, the timing of laser use in conjunction with respiration, and the concentration of
oxygen in the anesthesia mix. The ultimate decision about the technique of anesthesia
should be shared between the anesthesiologist and the surgeon when using an
endotracheal tube. The smallest possible laser-safe endotracheal tube should be used that
allows for adequate ventilation. If a cuffed tube is necessary, then the cuff should be
filled with saline so that, if it is inadvertently struck by the laser beam, the saline acts as a
heat sink and fire extinguisher. Some surgeons prefer to use methylene blue-colorized
saline to provide an additional warning in case the cuff is penetrated. The laser-ignited
airway explosion is a shocking emergency. Prompt, appropriate management is facilitated
if the OR team has previously rehearsed and discussed this potential disaster.
Operative Technique
After informed consent has been obtained from the appropriate family members,
including a discussion regarding potential laser complications, the child is brought back
into an OR that has been prepared and inspected by the surgeon and the laser team. When
performing surgery for RRP, it is advisable to have an experienced team of OR nurses
familiar with the sequence in which equipment is used and instructed in the proper use of
the laser. In our facility we also have a laser safety team and provide yearly updates for
the OR staff to ensure everyone's familiarity with the equipment and its potential
complications. All of our pediatric anesthesiologists are familiar and comfortable with
microlaryngoscopy laser surgery in children. However, in a nonchildren's hospital or
nonacademic setting if there are but one or two anesthesiologists experienced with these
techniques, then whenever possible they should be exclusively used. This type of surgery
is not well suited to the novice surgeon, anesthesiologist, or OR nurse. It is our practice to
insist that the attending anesthesiologist be present and involved hands on with all
critical portions of the surgical procedure, including induction, securing of the
endotracheal tube, positioning of the patient, changing of anesthesia techniques from a
laser-safe tube to apnea technique, and extubation.
In our facility the laser team consists of a scrub nurse, a circulating nurse, and a laser
nurse. The laser is the responsibility of the laser nurse, allowing the circulator and scrub
nurse to concentrate on their duties. All OR personnel are equipped with micropore laser
filtration masks and approved goggles. The room is set up in advance with a suspension
microlaryngoscope (Lindholm), a full set of Parson laryngoscopes (Karl Storz Endoscopy
America, Culver City, CA), two appropriately sized ventilating bronchoscopes, and
7,200-A and 8,700-A Hopkins rod telescopes (Karl Storz Endoscopy America, Culver
City, CA). A microscope with a 400-mm lens is fitted with the Accuspot 710
micromanipulator. An assortment of suctions, alligators, cup forceps, and light cords, as
well as a pack of neuropatties and topical neosynephrine, are also standard. An
endoscopy video cart equipped with color television monitor, videocassette recorder,
three-chip camera, and xenon light source are also used. Still photography through the
endoscope is also available as needed. Additionally, a pediatric tracheotomy set is
brought into the room, although the pack is not opened.
The surgical sequence begins with the mask induction using halothane and the
establishment of intravenous access. Dexamethasone at 0.5 mg/kg and cefazolin at 20
mg/kg are routinely administered preoperatively. The larynx is exposed using the Parson
laryngoscope attached to 6 L/min of oxygen flow through its insufflation port, and the
vocal folds are then sprayed with 2% lidocaine using a syringe attached to a Cass needle.
A diagnostic laryngoscopy is then performed using the 7,200-A telescope under video
control to assess the degree of papilloma disease and its encroachment on the laryngeal
airway. Depending on the extent of disease, the child's history, and the interval since the
last endoscopy, a full tracheoscopy and bronchoscopy also may be performed. Again,
depending on the child's level of preoperative and operative distress, the surgeon may
choose to perform this maneuver with either the 7,200-A telescope (if there is a low
likelihood of discovering distal disease) or with an appropriate size ventilating
bronchoscope (if there is high likelihood of discovering distal disease). Still photography
with the 8,700-A telescope is then performed at this stage, if desirable. If no distal disease
is present, then the patient may be intubated by the surgeon with a laser-safe tube (metal
Xomed-Treace, Medtronics, Minneapolis) of the smallest caliber that will allow the
anesthesiologist adequate ventilation. Once the airway has been secured with the
endotracheal tube, then the anesthesiologist is given the option to administer muscle
relaxants. As an alternative, the child may be maintained on propofol. It should be
stressed that no muscle relaxants are administered until the surgeon has assessed the
degree of laryngeal obstruction and ascertained that the airway has been secured. This
precaution serves to prevent the situation in which the child has lost his respiratory drive
and obstructs his airway with papilloma and/or blood or mucus, precipitating hypoxia and
a possible laryngospasm. Once the airway has been secured, the endotracheal tube is
taped in place with a single piece of tape (allowing the surgeon easy access for removal
of the endotracheal tube in the case of an airway fire) and the child suspended for
microlaryngoscopy with the microlaryngoscope. I prefer to suspend the
microlaryngoscope to a Mayo stand attached to the OR table. This device allows the
microsuspension system to be moved along with the patient and allow angulation of the
laryngoscope over a 120-degree range. The child's eyes are then protected against any
stray laser beam exposure with moist saline-soaked gauze eye pads. Lubricant is placed
in the eyes and the operative field is draped with moistened towels. Operating room
personnel are all equipped with ocular protection, including side shields, and a sign is
posted outside the OR warning that a laser procedure is in progress. A spare set of safety
glasses is left outside the door for OR personnel who wish to come inside the room while
the laser is in operation. Special laser masks with extremely small pores are worn to
minimize exposure to the laser plume. A high-volume smoke evacuator is attached to one
port of the microlaryngoscope to collect the laser plume. A second suction attached to the
smoke evacuator is used by the surgeon. By this point, the inspired FIO
2
delivered to the
patient should be as close to a room-air mixture as possible. Ideally, the laser is not used
until the oxygen in the mixture is between 26% and 30%. In selected circumstances, it
may be warranted to proceed with an FIO
2
at or below 40%. These precautions are taken
to minimize the possibility of a laser-induced endotracheal tube fire.
As an initial procedure, a microcup forceps is used for obtaining a biopsy specimen from
the bulkiest portion of papilloma. I use the Accuspot laser at initial settings of 4 watts
power, 0.1-second intervals, and repeat mode. Bulky papilloma is handled by defocusing
the laser. Moistened neuropatties are placed in the subglottis to decrease the air leak and
to provide a backstop for errant laser shots. These must be kept moist because they too
can act as a source of combustion. With the laser refocused, lesions are gradually
vaporized to the level of the mucosa, avoiding entry into Reinke's space and the deeper
vocalis muscle. I prefer using low-power settings to limit thermal injury to the
surrounding tissue, although this results in longer operating time. A small-caliber suction
device is kept close to the laser impact site to remove the hot steam of vaporization and to
remove eschar. Neuropatties soaked in neosynephrine are also used for removal of eschar
and debris as well as hemostasis. The blunt tip of the suction can be used as a probe and
retractor of the false cord or to roll the true cord for exposure of the subglottic region.
Care is taken to avoid injuring the anterior commissure, and at least 1 mm of untreated
mucosa should be left in this region so that a web does not develop during the healing
period. Similar considerations are taken for the posterior commissure. I normally begin
the procedure with removal of papillomas in the supraglottic larynx followed by the
anterior half of both true vocal cords. If disease has been noted in the posterior half of the
glottis or in the subglottic region, then I find that the endotracheal tube obstructs
exposure to these areas of the operative field and I seek an alternative means of
anesthesia. I prefer an apneic technique whereby the endotracheal tube is removed
intermittently and work is performed while the patient's oxygen saturation is monitored.
Another alternative would be spontaneous ventilation, although I find increased
circulation of anesthesia gases into the OR with this technique to be an undesirable side
effect. Many centers prefer the use of jet ventilation and sevoflurane. I have found all of
these techniques to be workable. Once a decision is made to go apneic, the
anesthesiologist increases the FIO
2
to 100%. The child is extubated but not unsuspended
from the microlaryngoscope, and the smoke evacuation port of the microlaryngoscope is
disconnected and oxygen tubing connected to this port to initiate flow of 6 L/min of O
2
.
While utilizing an apneic technique, the laser is used for 90- to 120-second intervals
initially and the child reintubated with a polyvinyl chloride endotracheal tube directly
through the microlaryngoscope, using a stylet to stiffen the tube and improve the
angulation. The CO
2
and O
2
levels are closely monitored and the length of laser on time
is adjusted appropriately. Typically, the child is reoxygenated for the same period of time
that he or she was apneic before proceeding with the next cycle. At the end of the case,
the child is reintubated with a standard endotracheal tube using a Selinger technique to
avoid any difficulty in reestablishing the airway upon removal of the microlaryngoscope.
The child is then extubated only when fully awake. High humidity and, occasionally,
racemic epinephrine are administered postoperatively in the recovery room. The patient is
then closely monitored for several hours prior to discharge, and often an overnight stay in
a monitored bed unit is necessary. As a general rule, the more extensive the papilloma
disease and the more compromised the airway, the more important it is for the child to be
monitored postoperatively in an intensive care or step-down unit. Additional doses of
steroids can be administered at 6-hour intervals if needed, and continuous pulse oximetry
is mandatory.
Another anesthetic alternative is the use of jet ventilation for microsurgery of the larynx.
Jet ventilation eliminates the potential fire hazard of the endotracheal tube and allows
good visualization of the vocal cords. A limitation of this technique is the possibility of
transmission of HPV particles into the distal airway. The jet cannula can be placed either
above or below the vocal cords and each has its own particular benefit. I prefer placement
of the cannula proximal to the end of the laryngoscope to decrease the risk of possible
pneumothorax or pneumomediastinum. With large laryngeal lesions, narrowed airways,
and ball-valve lesions, a high degree of outflow obstruction may develop that could lead
to increased intrathoracic pressure and a subsequent pneumothorax. This also may result
if there is inadequate muscle relaxation. Jet ventilation also requires constant
communication between the operating surgeon and the anesthesiologist. Excessive
mucosal drying and damage can occur, as can insufflation of air into the stomach with
gastric distention. As mentioned, there is also the potential risk of disseminating
papilloma or blood into the tracheobronchial tree.
Postoperative Care
Children with stable papilloma disease requiring fewer than four laser procedures per
year and whose parents reliably bring them in before showing signs of respiratory distress
can be monitored at home with commercially available infant home intercom-type
monitors. Those with rapidly reforming papillomas and those whose parents wait until
the child is in distress before seeking medical attention may warrant home pulse oximetry
with frequent home health visits. Children with RRP are encouraged to return to the
office or call as often as necessary. I give them carte blanche within my practice and
explain to them that their children have a special problem that allows them access to
speak with the doctors and nurses and show up unexpected to the office whenever they
feel their child is in need. I have yet to experience a family that has abused this privilege
and, on the contrary, it has enhanced their trust in the health care team and has avoided
urgent and emergent laser procedures.
Recurrent Respiratory Papillomatosis Staging
It is helpful when tracking the progression of a child's disease, communicating with other
surgeons, and treating patients in a protocol format to have a surgical scoring system to
assess severity and clinical course of RRP disease. Although several scoring and staging
systems have been proposed, clinicians and researchers have not yet adopted a uniformly
acceptable nomenclature for describing RRP lesions that is simple yet comprehensive.
This has created confusion in the RRP literature and in physician-to-physician
communications regarding patient's response to therapies. In addition, the absence of a
universally accepted staging system has hampered our abilities to accurately report the
results of adjuvant therapies or document the natural course of the disease. We have
proposed a new severity/staging system for RRP in a format that incorporates the best
qualities of the existing systems by numerically grading the extent of papillomatosis at
defined aerodigestive subsites, assesses functional parameters, diagrammatically catalogs
subsite involvement, and assigns a final numeric score to the patient's current extent of
disease (Fig. 85.3) (30). Using software designed at the University of Washington
(Seattle) and licensed to the American Society of Pediatric Otolaryngology, this staging
system is now computerized and available to pediatric otolaryngologists and
bronchoesophagologists to allow them to objectively and subjectively measure an
individual patient's clinical course and response to therapy over time. Encryption
technology with this software offers promise to allow clinicians from around the world to
anonymously share some of their patient data to enhance our knowledge of this disease
and promote multiinstitutional investigations.

FIGURE 85.3. Coltrera/Derkay staging and severity
scheme.



Adjuvant Treatment Modalities
Although surgical management remains the mainstay therapy for RRP, ultimately as
many as 10% of patients with the disease will require some form of adjuvant therapy. The
most widely adopted criteria for initiating adjuvant therapy are a surgery requirement of
more than four procedures per year, distal multisite spread of disease, and/or rapid
regrowth of papilloma disease with airway compromise. The most commonly
recommended adjuvant therapy is -interferon (Table 85.2) (4). The exact mechanism by
which interferon elicits its response is unknown. It appears to modulate host immune
response by increasing production of a protein kinase and endonuclease that inhibits viral
protein synthesis. Interferons are a class of proteins manufactured by cells in response to
a variety of stimuli including viral infection. The enzymes that are produced block the
viral replication of RNA and DNA and alter cell membranes to make them less
susceptible to viral penetration.

TABLE 85.2. ADJUVANT TREATMENT
MODALITIES FOR RRP



Common interferon side effects fall into two categories: acute reactions (fever and
generalized flulike symptoms, chills, headache, myalgias, and nausea that seem to
decrease with prolonged therapy) and chronic reactions (decrease in the growth rate of
the child, elevation of liver transaminase levels, leukopenia spastic diplegia, and febrile
seizures). Thrombocytopenia has been reported, as have rashes, dry skin, alopecia,
generalized pruritus, and fatigue. Acetaminophen has been found to effectively relieve
the fevers, and interferon injections are best tolerated at bedtime. Interferon produced by
recombinant DNA techniques appears to have fewer side effects and better efficacy than
blood bankharvested interferon. Therapy is initiated at 5 million units/m
2
body surface
area administered by subcutaneous injection on a daily basis for 28 days then 3
days/week for at least a 6-month trial. After 6 months in children with excellent
responses, and if side effects are severe, the dosage can be decreased to 3 million units/m
2

3 days/week with further slow weaning as tolerated.
Photodynamic therapy in the treatment of RRP has been studied extensively at Long
Island Jewish Hospital by Abramson, Shikowitz, and Steinberg (31). Photodynamic
therapy is based on the transfer of energy to a photo-sensitive drug. The original drug
used was dihematoporphyrin ether (DHE), which has a tendency to concentrate within
papillomas more so than in surrounding normal tissue. Patients are typically treated
intravenously with 4.25 mg/kg of DHE prior to photoactivation with an argon pump dye
laser. A small but statistically significant decrease in RRP growth, especially in those
patients with the worse disease, was seen with the use of photodynamic therapy and
DHE. The drawback of this therapy is that patients become markedly photo-sensitive for
periods lasting 2 to 8 weeks. A new drug, m-tetra (hydroxyphenyl) chlorine (Foscan,
Scotia Holdings, UK), has shown efficacy in HPV-induced tumors in rabbits with
minimal tissue damage and less photo-sensitivity. A clinical trial using this drug at a dose
of 0.15 mg/kg is currently under way. The preliminary results in adults are very
encouraging and children have now been added to the protocol.
Recent interest has focused on chemically pure indole-3-carbinol (I3C), a dietary
supplement not approved by the U.S. Food and Drug Administration (FDA), which has
been shown to inhibit papilloma formation in mice (32). This compound is found in high
concentration in cruciferous vegetables such as cabbage, broccoli, and cauliflower. A
small dietary study at Long Island Jewish Hospital showed promise, although there were
concerns regarding how much active drug the patients were actually receiving. Indole-3-
carbinol is now available in pure chemical form, and a current trial is ongoing at the
University of Pittsburgh. There are some concerns regarding whether the pure I3C will
maintain its effectiveness when taken with antacids or histamine (H
2
) blockers. A new
product, Photosorb-DIM, available in capsule form or as flavored sprinkles, is purported
to overcome this limitation. Preliminary data suggest a linear relationship between the
ratio of estrogen metabolism pathways (2-hydroxylation:16 -hydroxylation) and the
severity of RRP disease. Ratios of less than 1 are associated with severe disease and those
of greater than 3 are associated with mild disease. Rosen reported preliminary results in
18 children treated with pure I3C demonstrating safety and some efficacy, with 6 patients
sharing a complete response, 6 a partial response, and 6 no response (33).
Ribavirin is an antiviral drug, used to treat respiratory syncytial virus pneumonia in
infants, that also has shown some promise in the treatment of aggressive laryngeal
papillomatosis. Ostrow and co-workers at the University of Minnesota recently
completed a small trial in eight patients using ribavirin in an oral form at 23 mg/kg/day
divided four times daily after an initial intravenous loading dose. An increase in surgical
interval was seen in those treated (34).
Another antiviral treatment that has been advocated in the treatment of RRP is acyclovir.
Although the activity of acyclovir is dependent on the presence of virally encoded
thymidine kinase, an enzyme that is not known to be encoded by papillomavirus,
conflicting clinical results have been obtained in several small series. Theoretically, it
would not be expected to have a positive effect. However, it has been postulated that
perhaps acyclovir is most effective when there are codisease factors such as a
simultaneous infection with herpes simples virus. Such viral coinfections with herpes
simplex virus type 1, cytomegalovirus, and Epstein-Barr virus (HSV-1, CMV, and EBV)
have now been demonstrated in both adult (35) and pediatric (36) RRP patients. Adult
patients with viral coinfections appear to have a more aggressive clinical course.
Two recent reports have stimulated interest in the intralesional injection of cidofovir
(Vistide; HPMPC), a drug currently approved by the FDA for use in HIV patients with
CMV retinitis (Table 85.3). Among 17 patients with severe RRP treated with cidofovir at
2.5 mg/mL injected directly into the papilloma bed after laser surgery, Snoeck et al.
reported a complete response in 14 (37). Pranksy et al. have used this therapy in 10
children with severe RRP with short-term follow-up, reporting a response in 10 of 10
(38). Neither of these studies used a control group. Two open-label multisite protocols
have been initiated to further study the safety and efficacy of this promising drug.

TABLE 85.3. NEW HORIZONS UNDER
INVESTIGATION FOR RRP



Optimal control of extraesophageal reflux disease has been advocated as a means of
improving patient outcomes along with surgical therapy. Koufman and McGuirt have
reported anecdotal improvements in both children and adults with RRP who are
aggressively treated with H
2
blockers, proton pump inhibitors, and Nissen fundoplication.
A prospective clinical evaluation is currently under way at Bowman Gray to validate this
finding.
It should be stressed that participation in national and regional protocols of adjuvant
treatment modalities is essential for the scientific community to learn more about RRP. A
national registry of patients with RRP has been formed through the cooperation of the
American Society of Pediatric Otolaryngology and the CDC (7). The registry currently
tracks nearly 600 children at 22 sites with data on over 11,000 surgical procedures. It is
hoped that the national registry will aid in the identification of patients suitable for
enrollment in multiinstitutional studies of adjuvant therapies and will better define the
risk factors for transmission of HPV and the cofactors that may determine the
aggressiveness of RRP.

HIGHLIGHTS
Recurrent respiratory papillomatosis is a frustrating, capricious
disease with the potential for morbid consequences due to its
involvement of the airway and the risk of malignant
degeneration.
No single modality of therapy has been consistently shown
effective in eradicating RRP.
The goals of surgical therapy are to maintain a safe airway with
a serviceable voice while avoiding excessive scarring.
Many adjuvant therapies have been investigated to supplement
surgical therapy. These range from dietary supplements and
control of extraesophageal reflux disease to potent antiviral and
chemotherapeutic agents and photodynamic therapies.
Although several of these modalities have shown promise, no
adjuvant therapy to date has cured RRP.
Strides are being made in learning more about the natural
history of the disease through the establishment of a registry of
RRP patients at the CDC and the development of software to
help clinicians share information on and accurately follow their
RRP patients over time.
Future research is needed regarding prevention of transmission
of HPV from mother to child. Specifically, the roles of cesarean
section and gynecologic surgery during pregnancy need to be
elucidated. Development of an HPV vaccine and refinements in
surgical techniques to minimize laryngeal scarring also need to
be studied.
Surgical therapy for RRP requires a skilled team consisting of
otolaryngologists, anesthesia providers and OR personnel
working together in a facility properly equipped to manage
difficult pediatric airways.
Due to the recurrent nature of papilloma disease and the
potential for airway obstruction, parental support and education
can be invaluable to the safety of the child with RRP.
CHAPTER REFERENCES
1. Morgan AH, Zitsch RP. Recurrent respiratory papillomatosis in children: a retrospective study of
management and complications. Ear Nose Throat J 1986;65:1928.
2. Mounts P, Shah KV, Kashima H. Viral etiology of juvenile and adult onset squamous papilloma
of the larynx. Proc Natl Acad Sci U S A 1982;79:54255429.
3. Cohn AM, Kos JT, Taber LH, Adam E. Recurring laryngeal papilloma. Am J Otolaryngol
1981;2:129132.
4. Derkay CS. Task force on recurrent respiratory papillomas. Arch Otolaryngol Head Neck Surg
1995;121:13861391.
5. Kashima H, Shah F, Lyles A, et al. Factors in juvenile-onset and adult onset recurrent respiratory
papillomas. Laryngoscope 1992;102:913.
6. Shah KV, Stern WF, Shaf PK, et al. Risk factors for juvenile-onset recurrent respiratory
papillomatosis. Pediatr Infect Dis J 1998;17:372376.
7. Armstrong LR, Derkay CS, Reeves WC. Initial results from the National Registry for juvenile-
onset recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 1999;125:743748.
8. Rimell FL, Shoemaker DL, Pou AM, et al. Pediatric respiratory papillomatosis: prognostic role of
viral subtyping and cofactors. Laryngoscope 1997;107:915918.
9. Rihkaren H, Aaltonen LM, Syranen SM. Human papillomavirus in laryngeal papillomas and in
adjacent normal epithelium. Clin Otolaryngol 1993;18:470474.
10. Koutsky LA, Wolner-Hanssen P. Genital papillomavirus infection: current knowledge and future
prospects. Obstet Gynecol Clin North Am 1989;16:541561.
11. Ho GYF, Bierman R, Beardsley L, et al. Natural history of cervicovaginal papillomavirus
infection in young women. N Engl J Med 1998;338:423428.
12. Bennett RS, Powell KR. Human papillomavirus: association between laryngeal papillomas and
genital warts. Pediatr Infect Dis J 1987;6:229232.
13. Kashima H, Mounts P, Leventhal B, et al. Sites of predilection in recurrent respiratory
papillomatosis. Ann Otol Rhinol Laryngol 1993;102:580583.
14. Cummins MM, Koufman JA. Reflux and recurrent laryngeal papillomas. 2000 (in press).
15. Lindeberg H, Elbrond O. Laryngeal papillomas: the epidemiology in a Danish subpopulation
19651984. Clin Otolaryngol 1991;15:125131.
16. Puranen M, Yliskoski M, Saarikoski S, et al. Vertical transmission of human papillomavirus from
infected mothers to their newborn babies and persistence of the virus in childhood. Am J Obstet
Gynecol 1996;174:694699.
17. Smith EM, Johnson SR, Pignaari S, et al. Perinatal vertical transmission of human papilloma virus
and subsequent development of respiratory tract papillomatosis. Ann Otol Rhinol Laryngol
1991;100:479483.
18. Tseng C, Liang C, Soong Y, et al. Perinatal transmission of human papillomavirus in infants:
relationship between rate and mode of delivery. Obstet Gynecol 1998;91:9296.
19. Shah K, Kashima H, Polk BF, et al. Rarity of caesarean delivery in cases of juvenile-onset
respiratory papillomatosis. Obstet Gynecol 1986;68:795799.
20. Tenti P, Zappatore R, Migliora P, et al. Perinatal transmission of human papillomavirus from
gravidas with latest infections. Obstet Gynecol 1999;93:475479.
21. Kosko J, Derkay CS. Role of caesarean section in the prevention of recurrent respiratory
papillomas: is there one? Int J Pediatr Otolaryngol 1996;1:3138.
22. Shapiro AM, Rimell FL, Shoemaker D, et al. Tracheotomy in children with juvenile-onset
recurrent respiratory papillomatosis: the children's hospital of Pittsburgh experience. Am Otol
Rhinol Laryngol 1996;105:15.
23. Cole RR, Myer CM, Cotton RT. Tracheotomy in children with recurrent respiratory
papillomatosis. Head Neck 1989;11:226230.
24. Dean C, Sataloff RT, Hawkshaw M. Recurrent vocal fold papilloma: resection using cold
instruments. Ear Nose Throat J 1998;77:882884.
25. Zeitels SM, Sataloff RT. Phonomicrosurgical resection of glottal papillomatosis. J Voice
1999;13:123127.
26. Bower CM, Wanes M, Flock S, et al. Flash pump bye laser treatment of laryngeal papillomas. Ann
Otol Rhinol Laryngol 1998;107:10011005.
27. McMillan K, Shapshay SM, McGilligan JA, et al. A 585 n meter pulsed dye laser treatment of
laryngeal papillomas: preliminary report. Laryngoscope 1998;108:968.
28. Bergler W, Honig M, Gotte K, et al. Treatment of recurrent respiratory papillomatosis with argon
plasma coagulation. J Laryngol Otol 1997;111:381384.
29. Myer CM, Wiliging P, Cotton R. Use of a laryngeal microresector system. Laryngoscope
1999;109:11651166.
30. Derkay CS, Malis DJ, Zalzal G, et al. A staging system for assessing severity of disease and
response to therapy in recurrent respiratory papillomatosis. Laryngoscope 1998;108:935937.
31. Shikowitz MJ, Abramson AL, Freeman K, et al. Efficacy of DHE photodynamic therapy for
respiratory papillomatosis: immediate and long-term results. Laryngoscope 1998;108:962967.
32. Newfield L, Goldsmith A, Bradlow HL, et al. Estrogen metabolism and human papillomavirus-
induced tumors of the larynx:chemo-prophylaxis with indole-3-carbinol. Anticancer Res
1993;13:337341.
33. Rosen CA, Woodson GE, Thompson JW, et al. Preliminary results of the use of indole-3-carbinol
for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg 1998;118:810815.
34. Ostrow RS. Proceedings of 17th international papillomavirus conference.
35. Pou AM, Rimell FL, Jordan JA, et al. Adult respiratory papillomatosis: human papillomavirus
type and viral confections as predictors of prognosis. Am Otol Rhinol Laryngol 1995;104:758
762.
36. Stanley JJ, Robinson RA, Post JC, et al. Viral confections in Pediatric Respiratory Papillomatosis.
(in press).
37. Snoeck R, Wellens W, Desloovere C, et al. Treatment of severe laryngeal papillomatosis with
intralesional injections of Cidofovir. J Med Virol 1998;54:219225.
38. Pranksy SM, Magit AE, Kearns DB, et al. Intralesional Cidofovir for recurrent respiratory
papillomatosis in children. Arch Otolaryngol Head Neck Surg 1999;125:11431148.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

86 THE SYNDROMAL CHILD
Head & Neck SurgeryOtolaryngology
86




THE SYNDROMAL CHILD
RICHARD J. H. SMITH
JOSE M. MANALIGOD

R.J. H. Smith: Department of Otolaryngology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
J.M. Manaligod: Department of Otolaryngology and Head and Neck Surgery, University of Kentucky,
Chandler Medical Center, Lexington, Kentucky.


Definitions
Mendelian Inheritance Patterns
Nonmendelian Inheritance
Mosaicism
Uniparental Disomy
Genomic Imprinting
Mitochondrial Inheritance
Methods of Syndrome Diagnosis
Teratogens
Genetic Counseling
Specific Genetic Syndromes
Achondroplasia
Apert and Crouzon Syndromes
Branchiootorenal Syndrome
Down Syndrome
Fragile X Syndrome
Goldenhar Syndrome
Neurofibromatosis Type 1
Neurofibromatosis Type 2
Pierre Robin Sequence
Treacher Collins Syndrome
Usher Syndrome
Velocardiofacial Syndrome
Waardenburg Syndrome
Conclusions
Chapter References
Congenital abnormalities affect 3% of neonates; by the age of 5 years, as more subtle
anomalies manifest, the percentage climbs to 7% to 10% (1). Otolaryngologists should be
familiar with several common syndromes and have some knowledge of long-term
prognosis and recurrence risks. In this chapter, the terms applied to different congenital
anomalies are defined and several syndromes common to an otolaryngology practice are
described.
DEFINITIONS
To clarify nomenclature, an International Working Group of dysmorphologists
recommended a pathogenetically oriented classification system for congenital anomalies
in 1982 (2).
Association: A nonrandom occurrence in two or more individuals of multiple anomalies
not known to be a polytopic field defect, sequence, or syndrome. An example is
CHARGE association (colobomas, heart anomalies, atresia choanae, growth retardation,
genitourinary abnormalities, and ear malformations).
Deformation: An abnormal form, shape, or position of a part of the body caused by
mechanical forces. Examples include congenital torticollis and facial asymmetry that
arises from oligohydramnios and fetal crowding.
Disruption: A morphologic defect of an organ, part of an organ, or larger region of the
body resulting from the extrinsic breakdown of, or an interference of, an originally
normal developmental process. An example is facial clefting as a result of amniotic
bands.
Dysplasia: An abnormal organization of cells into tissues and its morphologic results. An
example is the coarse facies, corneal clouding, macroglossia, and skeletal abnormalities
of Hurler syndrome.
Malformation: A morphologic defect of an organ, part of an organ, or larger region of the
body resulting from an intrinsically abnormal developmental process. Examples include
isolated cleft lips and anencephaly.
Polytopic field defect: A pattern of anomalies derived from the disturbance of a single
developmental field. An example is velocardiofacial syndrome.
Sequence: A pattern of multiple anomalies derived from a single known or presumed
prior anomaly or mechanical factor. In the Pierre Robin sequence, the primary
abnormality, micrognathia, leads to glossoptosis, which causes cleft palate.
Syndrome: A pattern of multiple anomalies pathogenetically related but not representing
a single sequence or a polytopic field defect. A single cause for the physical
abnormalities is implied. Examples are branchiootorenal syndrome and Treacher Collins
syndrome.
MENDELIAN INHERITANCE PATTERNS
In 1865, Gregor Mendel demonstrated that separate units (genes) are inherited from each
parent and that the expression of these units depends on whether that trait is dominant or
recessive. A dominant trait requires only a single copy of the relevant gene to be
expressed; for a recessive trait, both copies of the relevant gene are necessary.
Autosomal-dominant inheritance shows a vertical pattern of trait expression (from one
generation to the next), male-to-male inheritance occurs, and males and females are
affected equally. The gene can be passed to progeny from either parent, and the relative
risk of an affected child is 50%. Examples of autosomal-dominant inheritance include
Waardenburg syndrome and Treacher Collins syndrome (Fig. 86.1).

FIGURE 86.1. Autosomal-dominant inheritance.
Vertical pattern of trait expression; males and females are
equally affected.



Autosomal-recessive inheritance shows a horizontal pattern of trait expression. Multiple
affected members usually are present in a single generation as progeny of the same
parents. Often, the parents are from a geographically isolated region or are related.
Expression of autosomal-recessive traits requires the inheritance of a mutated allele from
each parent. Each offspring has a 25% chance of being affected, a 50% chance of being a
carrier, and a 25% chance of being a noncarrier. Examples of autosomal-recessive
disorders include Usher syndrome and cystic fibrosis (Fig. 86.2).

FIGURE 86.2. Autosomal-recessive inheritance.
Horizontal pattern of trait expression. Parental
consanguinity is often present in families with autosomal-
recessive disorders.



X-linked inheritance is suggested when only males are affected. There is no male-to-male
transmission of the disorder, and males who are unaffected cannot pass on the disease
phenotype. All the female progeny of an affected male are carriers and will pass the
disorder to half their sons. Occasionally, a carrier female (heterozygote) will express
some aspects of the disease because of X-inactivation (Fig. 86.3).

FIGURE 86.3. X-linked recessive inheritance. Males
only are affected. There is no male-to-male transmission,
and daughters of affected males are carriers.



NONMENDELIAN INHERITANCE
Although mendelian inheritance has formed the basis for the discovery of many inherited
disorders, some hereditary traits are transmitted in a nonmendelian pattern that cannot be
classified as autosomal dominant, autosomal recessive, or X-linked.
Mosaicism
Mosaicism is defined by the presence of both normal and mutated cells within the same
organism. Somatic mosaicism arises when a genetic mutation occurs in a somatic
(nongermline) cell. The mutation is expressed in all the daughter cells that arise from the
original mutated cell, although the mutation cannot be passed to any of the carrier's
offspring. The severity of the stigmata of the syndrome varies with the proportion of cells
affected by the mutation.
Germline mosaicism arises when a person develops both normal and mutated germline
cells. If parents are phenotypically normal because they have no somatic cell genetic
abnormalities, only offspring will express the new mutation.
Uniparental Disomy
Uniparental disomy arises when both members of a chromosome pair are inherited from a
single parent, making it possible for an autosomal-recessive disease to be inherited from
only one carrier parent. Examples include rare persons with cystic fibrosis who have only
one carrier parent (Fig. 86.4).

FIGURE 86.4. Uniparental disomy. An example of both
a paternal and a maternal meiotic nondysjunction that
leads to the inheritance of both members of a
chromosome pair from a single parent.



Genomic Imprinting
A gene is imprinted if its expression depends on its parent of origin. Examples include
Prader-Willi and Angelman syndromes, which are both due to similar deletions on
chromosome 15q11-q13. Prader-Willi syndrome arises when the chromosome carrying
the deletion is of paternal origin, and Angelman syndrome results when the chromosome
with the deletion is of maternal origin. Other examples include cases of fragile X
syndrome, familial glomus cell tumors, and Beckwith-Wiedemann syndrome (Fig. 86.5).

FIGURE 86.5. Genomic imprinting. Inheritance of a
mutation (shaded black) on a paternal chromosome leads
to a specific phenotype (shaded gray). However,
inheritance of the same mutation from the corresponding
maternal chromosome causes expression of a different
and distinct phenotype (diagonal stripes).



Mitochondrial Inheritance
Each mitochondrion in the zygote derives from the ovum and carries several copies of
circular DNA. If a mutation is present in one of these mitochondrial chromosomes
(mitochondrial DNA, mtDNA), it can be passed on to daughter mitochondria that arise
from this mitochondrion. Because inheritance is maternal, all offspring, male and female,
who inherit affected mitochondria are at risk for expressing the trait. If all mitochondria
carry the mutation, a person is homoplasmic for the disorder; if normal and mutated
mtDNA exist, a person is heteroplasmic (Fig. 86.6). An example of a mitochondrial
disorder is maternally transmitted diabetes mellitus and deafness.

FIGURE 86.6. Mitochondrial inheritance. Inheritance
follows the maternal line. Individuals can be either
normal, heteroplasmic (both normal and mutated
mtDNA), or homoplasmic (all mtDNA are mutated).



METHODS OF SYNDROME DIAGNOSIS
A directed history should be taken noting whether similar birth defects have occurred and
recording on a detailed pedigree parental consanguinity and ethnicity, maternal and
paternal ages, possible teratogen exposure, and the outcome of prior pregnancies. It is
helpful to obtain an expanded pedigree and to review family photographs. The physical
examination should include an accurate description of auricular and facial malformations.
For example, dystopia canthorum differentiates Waardenburg syndrome type I and type
II.
Laboratory tests and karyotyping may be necessary for the diagnosis of a syndromal
child. The latter is recommended for any stillbirths or neonatal deaths to investigate the
possibility of a lethal syndrome for genetic counseling. DNA analysis using fluorescent
in situ hybridization can provide important information in specific situations such as
velo-cardio-facial syndrome. Skeletal and craniofacial radiographs are useful to evaluate
specific bony abnormalities.
A valuable tool accessible on the World Wide Web is Online Mendelian Inheritance in
Man (http://www3.ncbi.nlm.nih.gov/omim/). Other computer databases include
POSSUM and the London Dysmorphology Database. In most instances, using these
resources, a previously reported syndrome will be recognized and diagnosed; however,
about 30% of syndromal children will have a private syndrome. Irrespective of the
diagnosis, treatment of the specific disease components should be practiced, carefully
describing and documenting the key features of each condition.
TERATOGENS
Teratology is the study of environmentally induced birth defects or malformations.
Teratogens range from infectious agents to pharmaceutical agents, and may alter fetal
development in a recognizable pattern. Identifying a specific teratogen can aid in
determining the prognosis and treatment of a syndromal child. For example,
cytomegalovirus is an infectious teratogen that affects about 1% of all children born in
the United States. About 10% of these children are symptomatic and have microcephaly,
cerebral calcification, and chorioretinitis: 10% to 15% of the asymptomatically affected
children have signs of neurologic damage such as hearing impairment (3).
The most common pharmaceutical teratogen is alcohol. Fetal alcohol syndrome is the
most common cause of mental retardation in the United States, affecting 30% to 40% of
children born to alcoholic women (4). The syndrome is characterized by varying degrees
of mental retardation and developmental delay, with recognizable facial features
including microcephaly, epicanthal folds, an elongated and undefined philtrum, and a
flattened nasal dorsum (Fig. 86.7; see also Color Plate 29 following p. 496).

FIGURE 86.7. Fetal alcohol syndrome. Microcephaly,
flattened nasal dorsum, and elongated philtrum. (See also
Color Plate 29 following p. 496.)



GENETIC COUNSELING
Genetic counseling ensures that parents and relatives understand the implications of the
diagnosis. Information is presented in a nonjudgmental way, exploring issues such as
inheritance, prognosis, and recurrence risk. For children who have a known syndrome
that has a defined pattern of inheritance, recurrence risks are based on mendelian
genetics; however, when a child has a congenital malformation such as a cleft lip or
palate, counseling is often based on averaged recurrence rate data for the general
population. For example, there is a 3% to 5% recurrence risk in future children when one
child is born with a cleft lip/cleft palate. In these situations, it is important to stress that
this information is based on pooled data.
SPECIFIC GENETIC SYNDROMES
Because it is impossible in this chapter to outline the more than 3,000 characterized
genetic disorders, we have highlighted only a few common genetic disorders that have
specific otolaryngologic manifestations (Table 86.1).

TABLE 86.1. SYNDROME DIAGNOSIS



Achondroplasia
Achondroplasia is the most common cause of short-limb dwarfism. Although inheritance
follows an autosomal-dominant pattern, most cases result from spontaneous mutations,
with paternal age cited as a risk factor. Affected persons have shortened limbs, a long
narrow trunk, frontal bossing and mid-face hypoplasia, lumbar lordosis, limitation of
elbow extension, genu varum, and trident hand. There is usually no impairment of
cognitive function, although motor milestones may be delayed because of muscular
hypotonia. Obstructive sleep apnea and other respiratory abnormalities are common and
may require treatment (5). Brainstem compression can lead to central ventilatory
disorders, and with cervical spine compression at the craniovertebral junction, there is an
increased incidence of sudden death (6). The disease is caused by mutations in the
fibroblast growth factor receptor 3 gene (chromosome 4p16.3).
Apert and Crouzon Syndromes
Apert syndrome (acrocephalosyndactyly) and Crouzon syndrome (craniofacial
synostosis) are characterized by craniosynostosis, hypertelorism, exophthalmos, a parrot-
beaked nose, maxillary hypoplasia, and mandibular prognathism, with the added feature
of syndactyly in Apert syndrome (Fig. 86.8 and Fig. 86.9). Crouzon syndrome is slightly
more frequent (16.5 versus 15.5 per million births, respectively) and accounts for a higher
percentage of cases of craniosynostosis (4.8% versus 4.5%, respectively). Most cases of
Apert syndrome represent spontaneous mutations, although parent-to-child transmission
consistent with autosomal-dominant inheritance is reported; Crouzon syndrome is usually
autosomal dominant. Upper airway obstruction is a frequent problem (7), and with Apert
syndrome, fusion of the cervical vertebra also occurs (8). Cervical spine flexion and
extension views should be obtained prior to neck manipulation for general anesthesia.
Cognitive function ranges from severe mental retardation to normal intelligence. Both
syndromes are caused by mutations in fibroblast growth factor receptor 2, a gene that
maps to chromosome 10q26.

FIGURE 86.8. Apert and Crouzon syndromes are both
characterized by craniosynostosis, hypertelorism,
maxillary hypoplasia, and mandibular prognathism.



FIGURE 86.9. Apert syndrome has the additional feature
of syndactyly.



Branchiootorenal Syndrome
Branchiootorenal syndrome is an autosomal-dominant disorder characterized by
branchial cleft anomalies (cysts or fistulae), otologic malformations (preauricular pits,
malformed auricles, ossicular and cochlear malformations), and renal malformations
(renal agenesis, polycystic kidneys, duplicated ureters). The disease affects 2% of
children with severe to profound hearing impairment. The disease-causing gene is EYA1
(9) (Fig. 86.10).

FIGURE 86.10. Branchiootorenal syndrome. This 3-
year-old boy has visible cup-ear deformities. He also has
branchial cleft fistulae and only one kidney.



Down Syndrome
Down syndrome is the most common genetic disorder associated with mental retardation
and developmental delay. It occurs in 1 in 700 to 1,000 live births and affects up to
10,000 persons each year in the United States. Most cases are caused by trisomy of
chromosome 21, although translocations and mosaicism account for about 5% of cases
(10). Increasing maternal age is a known risk factor, with a 35- to 39-year-old woman
having 6.5 times the risk of having a child with trisomy 21 as a 20- to 24-year-old
woman; this figure escalates to 20.5% for a woman between 40 and 44 years of age (11).
Microcephaly, mid-face retrusion, upslanting palpebral fissures, epicanthal folds, and
macroglossia make diagnosis at birth relatively straightforward (Fig. 86.11; see also
Color Plate 30 following p. 496). A single palmar crease is often, but not always, present,
and 40% of affected children have congenital heart malformations. Some clinicians
recommend routine cardiac evaluations before the age of 9 months to detect surgically
correctable cardiac disease. Gastrointestinal tract abnormalities affect 12% of persons.

FIGURE 86.11. Down syndrome. Microcephaly,
epicanthal folds, and mid-face retrusion. (See also Color
Plate 30 following p. 496.)



Development of gross motor skills is delayed, and affected children usually do not sit
before the age of 12 months. The average age for walking development is 24 months.
Increased joint laxity contributes to joint dislocations, and coupled with
underdevelopment of the upper cervical vertebra, atlantoaxial subluxation or dislocation
is not uncommon. Significant atlantoaxial instability, defined as a 4- to 5-mm gap
between the atlas and the odontoid process when flexion and extension films are
compared, is found in 10% to 20% of affected children; 1% have symptoms of spinal
cord compression (12).
Fragile X Syndrome
Fragile X syndrome is the most common form of X-linked mental retardation and the
second most common genetic cause of mental retardation after Down syndrome. Affected
males have prominent ears, a large jaw, and a long face (Fig. 86.12). Speech is usually
high pitched and jocular, and behavior is hyperkinetic. Other features include
macroorchidism, joint hypermobility (especially digits), flat feet, and mitral valve
prolapse (13). The disease can manifest in carrier females (heterozygotes) as a decrease
in nonverbal IQ scores and the presence of some of the facial characteristics and finger-
joint hypermobility typical for the syndrome (14). The disease-causing gene is FMR1.

FIGURE 86.12. Fragile X syndrome. These two
individuals have prominent ears, elongated faces, and
jaws that are characteristic for fragile X syndrome.



Goldenhar Syndrome
Goldenhar syndrome (oculoauriculovertebral spectrum) is characterized by facial
asymmetry, unilateral external and middle ear deformities, and vertebral malformations.
Upper eyelid colobomas are often present, in contrast to the lower eyelid colobomas
found in Treacher Collins syndrome. Auricular malformations can range from mildly
deformed ears to complete anotia. Other otologic abnormalities include external canal
atresias and ossicular abnormalities. Isolated hemifacial microsomia is often placed
within the category of the oculoauriculovertebral spectrum because disease expression
can be very variable (Fig. 86.13). Most cases of Goldenhar syndrome are sporadic,
although autosomal-dominant inheritance has been reported (15).

FIGURE 86.13. Goldenhar syndrome. This 5-year-old
boy has facial asymmetry and right microtia.



Neurofibromatosis Type 1
Neurofibromatosis type 1 (NF1) has a prevalence of 1 in 3,000 to 4,000, making it one of
the most common hereditary disorders in children. It is characterized by caf au lait spots
and cutaneous neurofibromas, although there are numerous features including axillary
freckling, optic gliomas, Lisch nodules (iris hamartomas), and sphenoid wing dysplasia.
Simple neurofibromas usually occur after puberty; however, about 3% of affected
children develop cervicofacial plexiform neurofibromas, large tangled masses that
resemble a bag of worms intraoperatively (Fig. 86.14; see also Color Plate 31
following p. 496). Diagnostic criteria set down by the National Institutes of Health (NIH)
Consensus Development Conference require two or more of the following for a diagnosis
of NF1: (a) six or more caf au lait spots, the greatest diameter of which is more than 5
mm in prepubertal children and more than 15 mm in adolescents or adults; (b) two or
more neurofibromas of any type or one plexiform neurofibroma; (c) axillary or inguinal
freckling; (d) optic glioma; (e) two or more Lisch nodules; (f) osseous lesions such as
pseudoarthrosis of a long bone or spheroid wing dysplasia; or (g) a first-degree relative
with NF1 who fulfills these criteria (16).

FIGURE 86.14. Plexiform neurofibroma of the left facial
nerve of an individual with neurofibromatosis type I. (See
also Color Plate 31 following p. 496.)



Neurofibromatosis Type 2
Neurofibromatosis type 2 (NF2) is the central form of neurofibromatosis. It consists of
bilateral acoustic neuromas, meningiomas, and spinal cord schwannomas. Unlike NF1,
caf au lait spots and cutaneous neurofibromas are uncommon, and Lisch nodules are not
found, although posterior lens cataracts do occur. Mean age of presentation is 20, and
unilateral or bilateral hearing loss is one of the most common symptoms. Evans et al.
subdivided NF2 into two categories: the Wishart type (early onset and rapid growth, with
other fibromatous tumors other than acoustic neuromas), and the Gardner type (slower
rate of growth and onset and usually only bilateral acoustic neuromas) (17). Although
autosomal dominant, about 50% of cases represent de novo mutations. Criteria for its
diagnosis are (a) bilateral eighth nerve masses seen with appropriate imaging techniques
or (b) a first-degree relative with NF2 and either a unilateral eighth nerve mass or two of
the following: neurofibroma, meningioma, glioma, schwannoma, or juvenile posterior
subcapsular lenticular opacity (16).
Pierre Robin Sequence
Pierre Robin sequence is the triad of glossoptosis, micrognathia, and cleft palate. Long-
term follow-up shows that 25% of affected infants are assigned to a known syndrome,
most commonly Stickler syndrome (flat mid-face, cleft palate, retinal detachment,
cataracts, and arthropathy) (18). If the phenotype suggests Stickler syndrome, regular
ophthalmologic examinations are necessary to prevent complications from retinal
detachment and cataract formation (Fig. 86.15).

FIGURE 86.15. Pierre Robin sequence. This infant
required a tracheostomy because of airway compromise
from severe micrognathia.



Treacher Collins Syndrome
Treacher Collins syndrome (mandibulofacial dystosis) is an autosomal-dominant disorder
that occurs once in every 50,000 live births. Forty percent of cases arise in pedigrees with
a positive family history, and 60% represent new mutations. Hallmark features include
external and middle ear anomalies, zygomatic and mandibular hypoplasia, downslanting
palpebral fissures, lower lid colobomas, and cleft palate (19) (Fig. 86.16). Fifty percent
have hearing impairment from ossicular malformation or external auditory canal atresia,
the surgical correction of which can be extremely difficult (20). The disease-causing gene
is TREACLE.

FIGURE 86.16. Treacher Collins syndrome. Zygomatic
and mandibular hypoplasia, lower lid colobomas, and
downslanting palpebral fissures.



Usher Syndrome
Usher syndrome is characterized by sensorineural hearing loss and retinitis pigmentosa
and represents the most common cause of combined deafness/blindness in the Western
world. Three types of Usher syndrome exist: Ush1, characterized by profound congenital
sensorineural hearing loss, vestibular dysfunction, and retinitis pigmentosa; Ush2,
characterized by congenital mild to moderate sensorineural hearing loss, normal
vestibular function, and retinitis pigmentosa; and Ush3, characterized by progressive
sensorineural hearing loss, progressive vestibular dysfunction, and retinitis pigmentosa
(21). Each type is subgrouped based on different genetic loci.
Velocardiofacial Syndrome
Velocardiofacial syndrome can be recognized by typical facial features, including
almond-shaped palpebral fissures, deficient nasal alae, a tubular nose with a bulbous
nasal tip, and a small mouth. The degree of palatal clefting can range from small
submucous clefts to wide overt cleft palates (22). In persons with the former, an
adenoidectomy will invariably lead to velopharyngeal insufficiency (VPI). Usually, some
degree of hypernasal speech can be appreciated preoperatively and should be a clear
indication to avoid adenoidectomy. VPI can be corrected by pharyngeal flap surgery;
medial displacement of the internal carotid arteries is present in up to 25% of cases (23)
(Fig. 86.17).

FIGURE 86.17. Velocardiofacial syndrome. Broad nose,
triangular face, palatal incompetence.



Waardenburg Syndrome
Waardenburg syndrome is characterized by heterochromia irides, white eyelashes, a
white forelock, and sensorineural hearing loss; dystopia canthorum also can occur. The
latter feature distinguishes Waardenburg syndrome type I from Waardenburg syndrome
type II (Fig. 86.18). Waardenburg syndrome type III, also known as Klein-Waardenburg
syndrome, is characterized by blue eyes, hearing impairment, upper limb skeletal
dysplasias, and muscular hypotonia (24,25).

FIGURE 86.18. Waardenburg syndrome. This mother
and daughter have Waardenburg syndrome type I. Both
have hearing loss and dystopia canthorum. The child also
has heterochromia irides.



CONCLUSIONS
The diagnosis and care of the syndromal child can be a difficult yet satisfying challenge
for the otolaryngologist. Advances in molecular genetics are making DNA mutational
analysis increasingly important and require the otolaryngologist to become more
comfortable with genetics and genetic diseases. Added knowledge about the actual
mechanisms by which mutations cause errors in morphogenesis eventually may lead to
new therapies for some of these disorders.

HIGHLIGHTS
Autosomal-dominant inheritance has a vertical pattern of trait
expression and male-to-male inheritance, with males and
females being equally affected. The relative risk of an affected
child is 50%.
Autosomal-recessive inheritance has a horizontal pattern of trait
expression and multiple affected members. Each offspring has a
25% chance of being affected, a 50% chance of being a carrier,
and a 25% chance of being a noncarrier.
X-linked inheritance is suggested when males only are affected,
no male-to-male transmission of the disorder occurs, and
unaffected males cannot pass on the disease phenotype. All
female progeny of an affected male are carriers.
Mosaicism, uniparental disomy, genomic imprinting, and
mitochondrial inheritance are common causes of nonmendelian
inheritance.
Down syndrome is the most common genetic disorder
associated with mental retardation. Fragile X syndrome is the
most common form of X-linked mental retardation and the
second most common genetic cause of mental retardation.
Ten percent to twenty percent of children with Down syndrome
have atlantoaxial instability, and 1% have symptoms of spinal
cord compression.
Usher syndrome is the most common cause of combined
deafness/blindness in the Western world.
Lateral displacement of the medial canthi (dystopia canthorum)
is present in Waardenburg syndrome type I and absent in
Waardenburg syndrome type II.
CHAPTER REFERENCES
1. Baird PA, Anderson TW, Newcombe HB, et al. Genetic disorders in children and young adults: a
population study. Am J Hum Genet 1988;42:667693.
2. Spranger J, Benirschke K, Hall JG, et al. Errors of morphogenesis: concepts and terms,
recommendations of an International Working Group. J Pediatr 1982;100:160165.
3. Nankervis GA, Bhumbra NA. Cytomegalovirus infection of neonate and infant. Adv Pediatr Infect
Dis 1986;1:6174.
4. Abel EL, Sokol RJ. Incidence of fetal alcohol syndrome and economic impact of FAS related
anomalies. Drug Alcohol Depend 1987;19:5170.
5. Waters KA, Everett F, Sillence DO, et al. Treatment of obstructive sleep apnea in achondroplasia:
evaluation of sleep, breathing, and somatosensory-evoked potentials. Am J Med Genet
1995;59:460466.
6. Hecht JT, Francomano CA, Horton WA, et al. Mortality in achondroplasia. Am J Hum Genet
1987;41:454464.
7. Sirotnak J, Brodsky L, Pizzuto M. Airway obstruction in the Crouzon syndrome: case report and
review of the literature [Review]. Int J Pediatr Otorhinolaryngol 1995;31:235246.
8. Kreiborg A, Barr M Jr, Cohen MM Jr. Cervical spine in the Apert syndrome. Am J Med Genet
1992;43:704708.
9. Abdelhak S, Kalatzis V, Heilig R, et al. A human homologue of the drosophila eyes absent gene
underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nature Genet
1997;15:157164.
10. Stoll C, Alembik Y, Dott B, et al. Epidemiology of Down syndrome in 118,265 consecutive births.
Am J Med Genet 1990;7(suppl):7983.
11. Hook EB, Fabia JJ. Frequency of Down syndrome in live births by single year maternal age
interval: Results of a Massachusetts study. Teratology 1978;17:223228.
12. Davidson RG. Atlantoaxial instability in individuals with Down syndrome: a fresh look at the
evidence. Pediatrics 1988;81:857865.
13. Opitz JM, Sutherland GR. International workshop on the fragile X and X-linked mental
retardation. Am J Med Genet 1984;17:594.
14. Loesch DZ, Hay DA. Clinical features and reproductive patterns in fragile X female
heterozygotes. J Med Genet 1988;25:407414.
15. Regenbogen L, Godel V, Goya V, et al. Further, evidence for an autosomal dominant form of
oculoauriculovertebral dysplasia. Clin Genet 1982;21:161167.
16. Stumpf DA, Alksne JF, Annegers JF, et al. Neurofibromatosis conference statement. Arch Neurol
1988;45:575.
17. Evans DGR, Huson SM, Donnai D, et al. A clinical study of type 2 neurofibromatosis. Q J Med
1992;84:603618.
18. Sheffield LJ, Reiss JA, Strohm K, et al. A genetic follow-up study of 64 patients with the Pierre
Robin complex. Am J Med Genet 1987;28:2536.
19. Frazen LE, Elmore J, Nadler HL. Mandibulo-facial dysostosis (Treacher Collins syndrome). Am J
Dis Child 1967;113:406410.
20. Marres HA, Cremers CW, Marres EH, et al. Ear surgery in Treacher Collins syndrome [Review].
Ann Otol Rhinol Laryngol 1995;104:3141.
21. Smith RJ, Berlin CI, Hejtmancik JF, et al. Clinical diagnosis of the Usher syndromes. Usher
Syndrome Consortium. Am J Med Genet 1994;50:3238.
22. Williams MA, Shprintzen RJ, Rakoff SJ. Adenoid hypoplasia in the velo-cardio-facial syndrome.
J Craniofac Genet Dev Biol 1987;7:2326.
23. Lipson AH, Yuille D, Angel M, et al. Velocardiofacial (Shprintzen) syndrome: an important
syndrome for the dysmorphologist to recognize. J Med Genet 1991;28:596604.
24. Liu X-Z, Newton VE, Read AP. Waardenburg syndrome type II: phenotypic findings and
diagnostic criteria. Am J Med Genet 1995;55:95100.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

87 PEDIATRIC MALIGNANCIES
Head & Neck SurgeryOtolaryngology
87




PEDIATRIC MALIGNANCIES
Mark E. Gerber
Robin T. Cotton

M.E. Gerber: Department of Pediatric Otolaryngology, Children's Memorial Hospital, Chicago, Illinois.
R.T. Cotton: Department of Pediatric Otolaryngology, Children's Hospital Medical Center, Cincinnati,
Cincinnati, Ohio.


Hodgkin Disease
Epidemiology
Clinical Presentation
Pathology/Classification
Diagnosis and Staging
Treatment
Non-Hodgkin Lymphoma
Epidemiology
Clinical Presentation
Pathology
Diagnosis and Staging
Treatment
Sarcomas
Rhabdomyosarcoma
Thyroid Carcinoma
Epidemiology
Presentation
Pathology
Diagnosis and Staging
Treatment
Nasopharyngeal Carcinoma
Neuroblastoma
Conclusion
Chapter References
Whereas most head and neck masses in children are inflammatory or congenital in origin,
cancer ranks second to trauma as a cause of childhood mortality, with about 5% to 10%
of primary malignancies in the pediatric age group originating in the head and neck and
25% eventually involving the head and neck (1,2). The most common presentation of a
malignancy of the head and neck in children is an asymptomatic mass. Therefore, despite
the relative infrequency of pediatric head and neck malignancy, early recognition requires
a high index of suspicion. Clinical factors suggesting that a mass may be a malignant
process include onset in the neonatal period, rapid or progressive growth, skin ulceration,
fixation to underlying structures, cranial neuropathies, venous engorgement, associated
weight loss, or a firm mass greater than 3 cm in diameter. Other factors that increase the
chances of malignancy include a family history of childhood cancer, a previous primary
neoplasm, a known systemic cancer predisposition, and exposure to radiation therapy or
carcinogenic or immunosuppressive drugs (3,4).
Overall, the most common pediatric head and neck malignancies are Hodgkin disease and
non-Hodgkin lymphoma, followed by rhabdomyosarcoma and other sarcomas (Table
87.1) (2,5,6 and 7). The frequency of the various malignancies varies with the age of the
patient. Malignant teratomas and neuroblastomas tend to occur as congenital lesions or in
neonates and very young children. Rhabdomyosarcomas predominate in the preschool
years; non-Hodgkin lymphomas predominate during preadolescence. Hodgkin disease,
thyroid carcinoma, and salivary gland malignancies all are more likely to occur during
adolescence. In contrast to adults, epidermoid malignancies in children are rare (2).

TABLE 87.1. PEDIATRIC HEAD AND NECK
MALIGNANCIES



HODGKIN DISEASE
Epidemiology
Hodgkin disease is a lymphoreticular malignancy that has a bimodal incidence; the first
peak occurs between the ages of 15 and 34 years, the second peak in later adult years.
Hodgkin disease shows wide heterogeneity with respect to age, gender, geographics,
social class, and histologic subtype (8). The male-to-female ratio is 2:1. Epstein-Barr
virus (EBV) appears to be associated in 40% of cases. Whether EBV plays a direct role in
the pathogenesis or is simply a marker of a more basic immune disruption is unknown
(9). There is a higher incidence in developed countries. Other risk factors for the
development of Hodgkin disease include a small set of siblings, increasing maternal
education level, and the malignancy occurring in a sibling or to a lesser degree in any
first-degree relative (9).
Clinical Presentation
More than 80% of patients with Hodgkin disease present with cervical adenopathy. The
classic presentation is asymmetric, firm, rubbery, and nontender lymphadenopathy.
Extranodal primary sites are rare. Involvement of mediastinal lymph nodes is common
and may result in compression of the tracheobronchial tree or superior vena cava with
their associated manifestations. Systemic symptoms, including fever, night sweats, and
weight loss, are present in 30% to 40% of patients (3,9).
Pathology/Classification
The diagnosis of Hodgkin disease is based on the finding of the malignant Reed-
Sternberg cells surrounded by a background of benign inflammatory cells. The Reed-
Sternberg cell has two or more nuclei or nuclear lobes and two or more large nucleoli.
Their presence is necessary but not pathopneumonic, because they can be seen in other
lymphomas, carcinomas, and some benign conditions (9).
The Rye classification is the most commonly used system for classifying Hodgkin
disease (Table 87.2) (10). Within this system, the ratio of neoplastic to reactive cellularity
has prognostic significance. The prognosis is favorable when neoplastic cells are rare (as
in the lymphocyte-predominant subtype), poor when neoplastic cells predominate (as in
the lymphocyte-depleted subtype), and intermediate when the picture is more even (as in
the mixed-cellularity subtype). The presence of a nodular-sclerosing pattern is also more
favorable (9).

TABLE 87.2. RYE CLASSIFICATION OF
HODGKIN DISEASE



Diagnosis and Staging
Excisional biopsy of an involved lymph node is usually required to establish the
diagnosis. A fine-needle aspirate usually does not provide enough tissue to appreciate the
architecture of the lymph node fully, to exclude other diseases, and to subclassify the
disease (9). Initial evaluation should include a complete history (with an emphasis on
systemic symptoms of fever, night sweats, and weight loss of greater than 10% over the
past 6 months), physical examination (with special attention to all areas with palpable
lymph nodes), and blood tests (complete blood count with differential, erythrocyte
sedimentation rate, human immunodeficiency tests, tests for liver and renal function, and
serum alkaline phosphatase and lactate dehydrogenase levels) (9). Radiographic studies
usually include computed tomography (CT) of the chest and neck to include the
Waldeyer throat ring. Abdominal CT may be used to evaluate for involvement of the
spleen, liver, and lymph nodes; however, it is not a substitute for staging laparotomy
secondary to a high false-negative rate (11). Pathologic staging can include bone marrow
biopsy as well as specimens obtained at staging laparotomy or thoracotomy, including
additional lymph nodes, splenectomy, and liver biopsies. Bone marrow biopsy and
staging laparotomy should be done when the results are likely to alter the clinical stage
and therefore the treatment protocol used.
The most common staging system for Hodgkin disease is a modification of the Ann
Arbor classification (Table 87.3) (12). At diagnosis, 10% to 15% of patients have stage I
disease, another 10% to 15% have stage IV disease, and the remaining 70% to 80% have
stage II or III disease. Systemic symptoms (suffix B) are present in approximately 40% at
diagnosis (9).

TABLE 87.3. ANN ARBOR SYSTEM FOR
STAGING HODGKIN DISEASE



Treatment
The predominant treatment for early-stage Hodgkin disease (stage I and IIA) is external
beam radiation therapy; the 10-year survival rate is 90% and the 10-year relapse-free
survival rate is 75% to 80% (13,14). In contrast, the main treatment for advanced
Hodgkin disease is combination chemotherapy alone; the complete response rate is
between 44% and 87%, and the long-term disease-free survival rate is at least 50% (9).
As therapy for Hodgkin disease has improved, there has been an increased interest in
defining and minimizing the early and long-term complications of treatment. The most
common late complication of radiation therapy is hypothyroidism, but there is also an
increased risk of thyroid cancer or other secondary malignancies. Radiation also can lead
to arrested bone growth in children who have not yet achieved full size, pulmonary or
pericardial fibrosis, or coronary artery changes that can lead to premature myocardial
infarction. Chemotherapy has been associated with cardiac dysfunction (doxorubicin),
infertility, and secondary acute leukemias (9).
Using combined modality therapy in children, with low-dose radiation therapy and
chemotherapy, has been shown to be equally effective while causing less growth
impairment (15). Therefore, in children who have not obtained full growth, low-dose
radiation therapy combined with multiagent chemotherapy is currently recommended.
For advanced disease, more intense and prolonged courses of chemotherapy are used (2).
NON-HODGKIN LYMPHOMA
Epidemiology
Non-Hodgkin lymphoma is also a solid primary neoplasm of the lymphoreticular system.
In contrast to Hodgkin disease, however, the incidence of non-Hodgkin lymphoma
increases steadily throughout life. In addition, for unknown reasons, the incidence of
pediatric non-Hodgkin lymphoma increased in the United States by nearly 30% between
1973 and 1991. In equatorial Africa, the Burkitt subtype of non-Hodgkin lymphoma
accounts for almost half of all childhood cancers. Non-Hodgkin lymphoma is twice as
common in whites than in blacks and has a male-to-female ratio of 2:1 to 3:1. Patients
with congenital or acquired immunodeficient states are at an increased risk for
developing non-Hodgkin lymphoma, and EBV appears to have a widespread role in the
pathogenesis (16).
Clinical Presentation
The clinical presentations of non-Hodgkin lymphoma in children vary depending on the
primary site, histologic subtype, and stage of disease. Adults usually have primary nodal
disease that presents as asymptomatic lymphadenopathy. In contrast, children typically
have rapidly growing extranodal disease that primarily involves the head and neck
(especially the Waldeyer throat ring) in 29% and the mediastinum in 26%. Waldeyer
throat ring involvement may mimic benign adenotonsillar hypertrophy, making early
diagnosis difficult. Rapidly growing tumors that arise in the head and neck or
mediastinum may present with respiratory distress or superior vena cava syndrome
secondary to airway or vascular compression.
Dissemination is hematogenous, and nearly two thirds of children have locally advanced
or metastatic disease at the time of diagnosis (16). Systemic symptoms of fever, weight
loss, and malaise also correlate with advanced disease. When the disease has spread to
the central nervous system, patients present with cranial nerve palsies, mental status
changes, or malignant pleocytosis. The presence of pancytopenia suggests bone marrow
involvement, and when more than 25% of the bone marrow is replaced with tumor cells,
leukemic transformation is considered to be present (16).
Pathology
Non-Hodgkin lymphomas are categorized as low, intermediate, or high grade on the basis
of their clinical aggressiveness; more than 90% of children have high-grade tumors.
There are three histologic subtypes of high-grade tumors in children: small noncleaved
cell (34%), which includes both Burkitt and non-Burkitt; lymphoblastic (29%); and large
cell (27%).
Burkitt lymphoma is a diffuse B-cell malignancy that has the classic starry sky pattern of
phagocytic histiocytes and tumor cells with multiple nucleoli and monoclonal surface
immunoglobulins of the immunoglobulin M (IgM) class. There is a non-Burkitt type of
small noncleaved cell tumor that has greater pleomorphism than the Burkitt type (4).
Lymphoblastic lymphomas are nearly always derived from immature T cells and have
some histologic similarities to lymphoblastic leukemia. Histology shows small
lymphoblasts with round or convoluted nuclei, distinct nuclear membranes,
inconspicuous nucleoli, and a scant rim of basophilic cytoplasm (16).
Large cell non-Hodgkin lymphoma represent a heterogeneous group of lymphocytic and
histiocytic tumors. In adults, about 80% are of B-cell origin; in children, the number of
tumors of T-cell, B-cell, or indeterminate origin are about equal. Anaplastic features of
abundant cytoplasm, atypical lobulated nuclei, and prominent nucleoli in sheets of
adherent cells, with sinusoidal invasion is present in about 30% (16).
Diagnosis and Staging
As with Hodgkin disease, definitive diagnosis of non-Hodgkin lymphoma requires
incisional (or excisional when possible) biopsy. In addition to a complete history and
physical examination, clinical staging requires a metastatic workup that includes a chest
radiograph, skeletal survey or bone scan, abdominal CT (staging laparotomy is not
routine), cerebrospinal fluid (CSF) analysis, and bone marrow biopsy in addition to blood
tests (complete blood count with a differential, human immunodeficiency virus test,
chemistry panel, and tests of liver function) (2,3,4,5,6,7,8,9,10,11,12,13,14,15 and 16).
Staging is based on a modification of the Ann Arbor classification of Hodgkin disease
(Table 87.4) (16). As with Hodgkin disease, the accuracy of staging is important because
the intensity and duration of treatment are based on risk of failure, which greatly
increases with advanced disease. The tumor burden (clinical stage and serum lactate
dehydrogenase concentration) is the most important predictor of outcome (17). The
greatest risk of failure in patients with Burkitt subtype is when central nervous system
involvement is present at the time of diagnosis (18). Bone marrow involvement or T-cell
or indeterminate immunophenotype are associated with a worse prognosis in patients
with the large cell subtype (16).

TABLE 87.4. STAGING FOR NON-HODGKIN
LYMPHOMA



Treatment
Because early hematogenous dissemination results in presentation at advanced stages,
systemic therapy is the primary treatment for childhood non-Hodgkin lymphoma, with
surgery limited to a diagnostic role. Radiation therapy is usually limited to emergency
situations involving airway, nervous, or vascular compromise. The intensity and duration
of chemotherapy vary markedly with the stage and histologic subtype of disease (Table
87.5). The prognosis is excellent for children who have limited (stage I or II) disease
regardless of subtype. Because of the excellent survival statistics in limited stage disease,
less toxic treatment protocols have been able to decrease the treatment-related morbidity,
including cardiomyopathy, sterility, and secondary malignancies. Advanced disease
treatment protocols and outcomes vary more depending on histologic subtype, with
prognosis for long-term disease-free survival ranging from 50% to 85% (16). Despite
significant improvements in outcome of advanced-stage non-Hodgkin lymphoma, nearly
30% of patients relapse or never achieve a first remission. Prognosis is generally poor for
children who relapse, and those who achieve a second remission are considered
candidates for bone marrow transplantation (16).

TABLE 87.5. OUTCOME OF STAGE-DIRECTED
IN CHILDREN WITH NON-HODGKIN
LYMPHOMA



SARCOMAS
Sarcomas are malignant tumors of mesenchymal cell origin. Specific types of sarcomas
are named according to the suspected tissue lineage, such as rhabdomyosarcoma (skeletal
muscle), leiomyosarcoma (smooth muscle), liposarcoma (fat), fibrosarcoma (connective
tissue), and others. Soft-tissue sarcomas are the sixth most common cancer in children;
the incidence of rhabdomyosarcoma is at least equal to that of all the other sarcomas
combined (19). The diagnostic approach to nonrhabdomyosarcoma soft-tissue sarcomas
is essentially the same as that of rhabdomyosarcoma. Because of their extreme rarity,
even taken as a group, there is no meaningful staging system to guide therapy. In most
cases, treatment is by wide local excision with postoperative irradiation and
chemotherapy reserved for gross or microscopic residual disease, treating recurrences,
and metastatic disease.
Rhabdomyosarcoma
Epidemiology
Rhabdomyosarcoma is the most frequent soft-tissue malignancy of childhood, with the
head and neck the most common sites (35% to 40%). Almost 50% of cases are diagnosed
in children 5 years of age or younger (20).
Clinical Presentation
The clinical presentation of patients with rhabdomyosarcoma will vary greatly depending
on the site of the primary tumor, the age of the patient, and the presence or absence of
metastatic disease (21). The most common sites in the head and neck in descending order
of frequency are the orbit, nasopharynx, middle ear/mastoid, and sinonasal cavity (2).
Parameningeal sites of origin are present in 18% of cases and include the middle ear,
nasal cavity, and paranasal sinuses (22). Presenting symptoms of head and neck
rhabdomyosarcoma include nasal airway obstruction, bloody rhinorrhea, otorrhea, and
proptosis. These nonspecific symptoms often mimic benign disease, leading to a delay in
the diagnosis. Multiple cranial nerve palsies or other neurologic findings suggest
extension of the disease to the base of the skull or the central nervous system.
Pathology
Rhabdomyosarcomas are divided into four groups based on histopathology. Embryonal
rhabdomyosarcoma and its botryoid variant account for 75% of head and neck cases and
are the two most common histopathologic types among infants and young children.
Alveolar rhabdomyosarcoma constitutes 20% of head and neck rhabdomyosarcomas and
occurs predominantly in adolescents. Pleomorphic rhabdomyosarcoma is largely a
disease of adults. Histologically, embryonal rhabdomyosarcoma is composed of spindle-
shaped cells that taper to bipolar or stellate processes and contain abundant eosinophilic
cytoplasm. These cells resemble rhabdomyoblasts and are grouped into interlacing bands
superimposed on a loose myxoid stroma. The botryoid variant of embryonal
rhabdomyosarcoma is unique in that it forms a condensed layer of cells immediately
beneath the mucosa and produces a polypoid lesion. Alveolar rhabdomyosarcoma is
characterized by small, round cells separated into alveolar groupings by fibrous septa. In
70% of cases, definitive evidence of striated muscle differentiation is not present with
light microscopy. Immunohistologic techniques and electron microscopy are therefore
needed to be able to classify the lesions as rhabdomyosarcomas (4).
Diagnosis and Staging
Evaluation of patients with rhabdomyosarcoma should include a CT scan and often a
magnetic resonance imaging scan of the head and neck. A CT scan of the chest, bone
scan, and bone marrow biopsies also should be done, because the most common sites of
metastatic spread are the lungs, bones, and bone marrow. When the primary site is
parameningeal, a lumbar puncture also should be done to evaluate CSF cytology.
The Clinical Grouping System, which is based on the idea that those lesions that could be
completely resected had a better prognosis, was used in Intergroup Rhabdomyosarcoma
Studies (IRS) I, II, and III (Table 87.6) (21). The definition of what is surgically
resectable varies greatly between institutions, making assessment of outcome difficult,
however. A newer staging system used in IRS-IV incorporates a nonsurgically based
system for staging the extent of disease present at the time of diagnosis (Table 87.7) (21).
The single most important prognostic factor is the presence or absence of metastatic
disease. Other factors associated with a better prognosis include smaller tumor size and
noninvasiveness, orbital primary site (within the head and neck), embryonal histology,
absence of regional lymph node involvement, complete resectability, and younger age at
diagnosis (2 to 10 years) (21).

TABLE 87.6. CLINICAL GROUP STAGING
SYSTEM FOR RHABDOMYOSARCOMA



TABLE 87.7. TNM PRETREATMENT STAGING
FOR THE INTERGROUP
RHABDOMYOSARCOMA STUDY-IV HEAD AND
NECK SITES



Treatment
Control of head and neck rhabdomyosarcomas is best achieved using multimodality
therapy. Prior to IRS-I, the 5-year survival for all head and neck rhabdomyosarcomas was
less than 20% (2). In IRS-II, the 5-year survival rate increased to 92% for orbital disease,
69% for parameningeal disease, and 81% for other head and neck sites (22) (Table 87.8).

TABLE 87.8. FIVE-YEAR SURVIVAL FOR
CHILDREN UNDER AGE 15, UNITED STATES,
19601992



IRS-I did show that complete resection of tumors has a large impact on survival;
however, because of the now proven efficacy of chemotherapy and radiation therapy at
eradicating residual disease, surgery that results in significant cosmetic or functional
impairment is no longer indicated. This is especially important in head and neck lesions
with the nearly universal juxtaposition to critical tissues. For this reason, treatment
requires a combination of surgery and radiation therapy. In a similar fashion, regional
(neck lymph nodes) disease requires surgery and postoperative radiation only for
pathologically positive involvement. In addition, almost all patients with head and neck
rhabdomyosarcoma are presumed to have at least microscopic amounts of metastatic
disease at diagnosis. Therefore, chemotherapy has become a part of every protocol, with
the extent and duration dictated by the risk of treatment failure.
Vast improvements have been made in the prognosis among patients with locally
extensive, unresectable, nonmetastatic disease who can expect a 60% to 70% rate of
long-term survival. The most feared long-term complication of treatment is the
development of second malignancies, which have been reported to occur in 1.7% of
patients (23).
THYROID CARCINOMA
Epidemiology
Thyroid carcinoma is a relatively uncommon neoplasm in the pediatric population,
occurring mainly in children 10 years of age and older. The female preponderance
present in adult thyroid carcinoma is present to a lesser degree in children.
Presentation
The overwhelming majority of pediatric patients with thyroid carcinoma present with an
asymptomatic firm and mobile anterior neck mass. Clinical signs and symptoms that
increase the risk of malignancy include a history of rapid growth, new-onset hoarseness,
odynophagia, hemoptysis, vocal cord paralysis, or fixation to surrounding tissues.
Palpable cervical lymph node metastases are present in three of four patients, and 5% to
10% have pulmonary metastases at the time of presentation (4).
Pathology
The vast majority of pediatric thyroid malignancies are of the differentiated type;
papillary malignancies are much more common than follicular. Regional lymph node
metastases are more common in the papillary type, whereas hematogenous dissemination
is more common in follicular carcinoma.
The major risk factor predisposing to differentiated thyroid carcinoma is exposure to
radiation. This risk was most dramatically underscored following the Chernobyl nuclear
disaster by the more than 100 cases observed in a region where no more than one to two
pediatric thyroid carcinomas per year had been previously identified (24,25). Genetic
factors also may play a role in well-differentiated thyroid carcinoma, because there is an
association with Gardner syndrome (familial colonic polyposis) and Cowden disease
(familial goiter and skin hamartomas) (26).
Although medullary thyroid carcinoma is relatively rare in both children and adults, 25%
to 30% are identified as familial: either part of multiple endocrine neoplasia (MEN) type
2A (medullary thyroid carcinoma and hyperparathyroidism), MEN type 2B (medullary
thyroid carcinoma, mucosal neuromas, and marfanoid-like features), or familial
medullary thyroid carcinoma. It is inherited as an autosomal-dominant feature of these
syndromes, with more than 90% of persons who inherit the gene for MEN type 2
developing medullary thyroid carcinoma at some point during life (26).
Diagnosis and Staging
The initial evaluation in a patient with a single thyroid nodule consists of thyroid function
studies, thyroid antibodies, serum calcium level, and a fine-needle aspiration of the
palpable nodule (26). Even though the role of fine-needle aspiration is not as well
established in children as in adults, improvements in cytologic analysis over recent years
have made it the single most helpful diagnostic test in the workup of a thyroid nodule.
Some history or physical examination findings may suggest medullary thyroid carcinoma
including hypertension, mucosal neuromas, and marfanoid features. In these patients,
laboratory evaluation needs to include an assessment for urinary catecholamines,
hypercalcemia, and hypercalciuria.
The incidence of thyroid carcinoma in children or adolescents with a solitary thyroid
nodule is as high as 40%; therefore, some advocate surgical biopsy of all solid nodules in
children (27); however, clinical judgment still needs to remain an important factor in
deciding on surgical intervention.
Treatment
When open biopsy is undertaken, the initial approach should be to perform a lobotomy on
the involved side, waiting for frozen-section confirmation of carcinoma before
proceeding with a near-total or total thyroidectomy. When neck disease is present,
functional neck dissection is performed to remove the lymphatic tissue in the paratracheal
area and levels II through IV. Thyroid hormone replacement should be withheld during
the initial postoperative period until a total-body iodine 131 scan with subsequent iodine
131 treatment of positive scans.
All persons identified to have medullary thyroid carcinoma require screening for the gene
carrier of MEN type 2 using DNA analysis. When one of the genetic mutations is present,
all family members should be screened, with those who are positive undergoing total
thyroidectomy around the age of 6 years for the MEN type 2A mutation and shortly after
birth for the MEN type 2B mutation (28).
Good prognostic factors in the treatment of differentiated thyroid carcinoma include
younger age at diagnosis, smaller size of primary tumor, absence of extrathyroid
extension, complete gross resection at initial surgery, and the absence of nodal or distant
metastases. The 5-year survival rate of pediatric patients with papillary and follicular
carcinomas approaches 100%, and the 20-year survival rate is in the range of 85%. In
contrast, the 20-year survival rate of patients with medullary carcinoma is about 40% (4).
NASOPHARYNGEAL CARCINOMA
Nasopharyngeal carcinoma is a rare neoplasm that in children occurs primarily in the
adolescent age group. It is classified according to the World Health Organization (WHO)
system into WHO I (keratinizing squamous), WHO II (nonkeratinizing squamous), and
WHO III (undifferentiated) (29). Most nasopharyngeal carcinomas in children are
undifferentiated. Histologic distinction between rhabdomyosarcoma, non-Hodgkin
lymphoma, and nasopharyngeal carcinoma can be difficult. An association between EBV
and both nonkeratinizing and undifferentiated nasopharyngeal carcinoma exists, with
titers correlating with tumor load. Most children present with asymptomatic metastatic
cervical disease. Common associated findings include unilateral otitis media, progressive
nasal airway obstruction, and rhinorrhea. Skull-base involvement is suggested by the
presence of cranial nerve palsies and headaches. Hematogenous spread to bone and liver
occurs early in the natural history, with distant metastases common at the time of
presentation (4).
Radiologic testing, usually in the form of CT, can provide an adequate assessment of the
extent of disease, including skull-base involvement. Undifferentiated nasopharyngeal
carcinoma is considered radiosensitive. Adjuvant chemotherapy may improve the
prognosis in some patients who have disseminated disease. Overall 5-year survival
approaches 40% in children with nasopharyngeal carcinoma. There is an improved
prognosis when the tumor is confined to the nasopharynx (3).
NEUROBLASTOMA
Neuroblastoma is a malignancy of the sympathetic nervous system that is commonly seen
in newborns and children younger than 10 years of age. It has a peak incidence at 2 years
of age.
Although it is the most common malignancy in infants under 1 year of age, fewer than
5% present with primary cervical lesions. Sixty percent of patients have metastases at
presentation. Metastatic disease to the head and neck is more common than primary
disease. Primary cervical neuroblastoma often presents early in life as a painless mass.
Horner syndrome, heterochromia iridis, and pressure symptoms related to the
aerodigestive tract may be present. Osseous metastases are common; favorite sites
include the calvarium, orbit, ribs, and long bones. Diagnostic evaluation should include
intravenous pyelography (which yields abnormal results in 80% of abdominal primary
tumors), chest radiographs, abdominal ultrasonography or CT, skeletal survey, liver-
spleen scan, and bone marrow aspirate. A special feature of neuroblastomas is their
association with elevated urine catecholamines. The level of urine vanillylmandelic acid
should be assessed (4).
Surgery is the treatment of choice for localized disease, and chemotherapy is used for
residual disease and metastatic disease. The improvement in survival rates with
chemotherapy seen in other childhood cancers has not been as dramatic in cases of
neuroblastoma. Adjuvant radiation therapy is helpful in unresectable disease. Prognosis
depends primarily on tumor size and the patient's age. When lesions can be completely
excised in patients under 1 year of age, survival is greater than 90%. In addition, primary
head and neck lesions have a better prognosis than other sites; however, the influence of
patient age and head and neck primary site may be due to the lesions being smaller and
not to the other factors alone (4).
CONCLUSION
Survival of children who have major head and neck malignancies has improved
remarkably (Table 87.8); however, along with these improvements has come an increased
incidence of long-term complications of treatment. Current efforts need to stress the
treatment of advanced and recurrent disease, for which the prognosis remains poor in
most of the above diagnosis. In addition, treatment regimens for those earlier stage
lesions that have better survival outcomes now need to attempt to decrease the treatment-
related morbidity and mortality while maintaining survival outcome.

HIGHLIGHTS
Head and neck sites account for 5% of childhood malignancies.
Lymphoma and rhabdomyosarcoma are the most common
childhood malignancies.
The most common sites for malignancies are the neck and the
oropharynx and nasopharynx.
The frequency of different types of malignancy varies with age.
Treatment depends on histology of the malignancy and extent
of disease.
Lymphoma is best managed with chemotherapy and radiation
therapy.
Rhabdomyosarcomas are treated by multimodality therapy.
Nasopharyngeal carcinoma is radiosensitive.
Thyroid carcinoma, neuroblastoma, and salivary gland tumors
are treated surgically.
The risk of secondary malignancy, recurrence, and growth
retardation mandate long-term follow-up after the treatment of
pediatric malignancy.
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18. Haddy TB, Adde MA, Magrath IT. CNA involvement in small noncleaved-cell lymphomas: is
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

88 ANATOMY AND PHYSIOLOGY OF THE EUSTACHIAN TUBE SYSTEM
Head & Neck SurgeryOtolaryngology
88




ANATOMY AND PHYSIOLOGY OF THE
EUSTACHIAN TUBE SYSTEM
CHARLES D. BLUESTONE

C.D. Bluestone: Department of Pediatric Otolaryngology, Children's Hospital of Pittsburgh, Pittsburgh,
Pennsylvania.


Anatomy of the Eustachian Tube System
Eustachian Tube Muscles
Infant Versus Adult Anatomy
Physiology of the Eustachian Tube
Protective and Clearance Functions
Model of Protective and Clearance Functions
Pressure Regulation Function
Chapter References
Knowledge of the anatomy and physiology of the eustachian tube is important for all who
are involved in the management of patients who have diseases and disorders of the
middle-ear cleft and its adjacent anatomic structures. This chapter describes not only the
anatomy and physiology of the tube but also information about how dysfunction of the
eustachian tube and related structures might result in abnormalities of the middle ear and
mastoid. Put very simply, the dysfunctional eustachian tube is either too closed, too
open, too short, too stiff, or won't open, but either end of the system may be
abnormal, which can result in middle-ear disease: either end of the system can be too
closed, too open, or develop abnormal pressures (1) (see also Chapter 82).
The eustachian tube should not be thought of as a separate entity from the structures that
surround it. The eustachian tube is part of a system of contiguous organs that includes the
nose, palate, and nasopharynx proximal to the eustachian tube, and the middle ear and
mastoid at its distal end (Fig. 88.1). In reality, the eustachian tube is not a tube but an
organ consisting of a lumen with its mucosa, cartilage, surrounding soft tissue, peritubal
muscles (i.e., tensor veli palatini, levator veli palatini, sal-pingopharyngeus, and tensor
tympani), and its superior bony support, the sphenoid sulcus (2).

FIGURE 88.1. The eustachian tube connects the nose
and nasopharynx with the middle ear and mastoid as a
system. (Redrawn from Bluestone CD, Klein JO. Otitis
media, atelectasis, and eustachian tube dysfunction. In:
Bluestone CD, Stool SE, Kenna MA, eds. Pediatric
otolaryngology, 3rd ed. Philadelphia: WB Saunders,
1996:399.)



ANATOMY OF THE EUSTACHIAN TUBE SYSTEM
The eustachian tube lumen is wider at both the proximal (nasopharyngeal) and distal
(middle ear) ends than in the mid-portion; the isthmus is the most narrow. A recent three-
dimensional study of nine human temporal bone specimens by Sudo and associates
demonstrated the isthmus portion of the lumen to be near the distal end of the
cartilaginous portion and not at the junction of the cartilaginous and osseous portions;
they named the segment where the cartilaginous and osseous portions connect as the
junctional portion, which was determined to be 3 mm in length in the adult (3). On the
lateral wall of the nasopharynx, a prominence, the torus tubarius, protrudes into the
nasopharynx. This prominence is formed by the abundant soft tissue overlying the
cartilage of the eustachian tube. Anterior to this is the triangular nasopharyngeal orifice
of the tube (Fig. 88.2A). From the torus, a raised ridge of mucous membrane, the
salpingopharyngeal fold, descends vertically. On the posterior wall of the nasopharynx lie
the adenoids, or pharyngeal tonsil, composed of abundant lymphoid tissue. Above the
tonsil is a variable depression within the mucous membrane called the pharyngeal bursa.
Behind the torus lies a deep pocket, extending the nasopharynx posteriorly along the
medial border of the eustachian tube. This pocket, the fossa of Rosenmller, varies in
height from 8 to 10 mm and in depth from 3 to 10 mm (4). Adenoid tissue usually
extends into this pocket, giving soft tissue support to the tube.

FIGURE 88.2. A: Complete dissection of the eustachian
tube and middle ear. Especially evident are the
relationships between the eustachian tube, paratubal
muscles, and cranial base, as well as the position of the
juncture between the osseous portion of the eustachian
tube and the middle ear. B: Relationship between the
superficial muscle bundle (tensor veli palatini) and the
deep bundle (dilator tubae) to the lateral wall of the
eustachian tube. C, cochlea; EAC, external auditory canal; I, incus; M, mastoid; Ma,
malleus; S, stapes; SC, semicircular canals; TM, tympanic membrane. (Redrawn from
Bluestone CD, Klein JO. Otitis media, atelectasis, and eustachian tube dysfunction. In:
Bluestone CD, Stool SE, Kenna MA, eds. Pediatric otolaryngology, 3rd ed. Philadelphia:
WB Saunders, 1996:400.)



In the adult, the eustachian tube is longer than in the infant and young child. Most of the
increase in length takes place before the age of six years (5). The eustachian tube has
been reported to be as short as 30 mm and as long as 40 mm, but the usual range of
length reported in the literature is 31 to 38 mm (4,6,7). It is generally accepted that the
posterior third (11 to 14 mm) of the adult tube is osseous and the anterior two thirds (20
to 25 mm) are composed of membrane and cartilage (4,8). In adults, the eustachian tube
lies at an angle of 45 degrees in relation to the horizontal plane, whereas in infants this
inclination is only 10 degrees (4).
The anatomy of the cranial base may be related to the length of the eustachian tube,
which may be related to a susceptibility for middle-ear disease (9).
The anatomic configuration of the eustachian tube and its relation to other structures are
presented in Fig. 88.2A. The osseous eustachian tube (protympanum) lies completely
within the petrous portion of the temporal bone and is directly continuous with the
anterior wall of the superior portion of the middle ear. The juncture of the osseous tube
and the epitympanum lies 4 mm above the floor of the tympanic cavity (8). This
relationship, although valid, is misrepresented in the more popular descriptions and
depictions of the eustachian tubemiddle ear juncture and is of some importance in the
functional clearance of middle-ear liquids.
The osseous portion of the tube (i.e., protympanic or middle-ear portion) has a course that
is linear anteromedially, following the petrous apex and deviating little from the
horizontal plane. The lumen is roughly triangular, measuring 2 to 3 mm vertically and 3
to 4 mm along the horizontal base. The healthy osseous portion is open at all times, in
contrast to the fibrocartilaginous portion, which is closed at rest and opens during
swallowing or when forced open, such as during the Valsalva maneuver. The osseous and
cartilaginous portions of the eustachian tube meet at an irregular bony surface and form
an angle of about 160 degrees with each other. The medial wall of the bony portion of the
eustachian tube consists of two partsposterolateral (labyrinthine) and anteromedial
(carotid)whose size, shape, and relationship depend on the position of the internal
carotid artery. The average thickness of the anteromedial portion is 1.5 to 3 mm, and in
2% of persons the wall is absent, exposing the carotid artery.
The cartilaginous tube then courses anteromedially and inferiorly, angled in most cases
30 to 40 degrees to the transverse plane and 45 degrees to the sagittal plane (8). The tube
is applied closely to the basal aspect of the skull and fitted to the sulcus tubae between
the greater wing of the sphenoid bone and the petrous portion of the temporal bone. The
cartilaginous tube is attached firmly at its posterior end to the osseous orifice by fibrous
bands and usually extends some distance (3 mm) into the osseous portion of the tube. At
its inferomedial end, it is attached to a tubercle on the posterior edge of the medial
pterygoid lamina (4,6,10).
The tube in its cartilaginous portion has a crook-shaped mediolateral superior wall (Fig.
88.2B). It is completed laterally and inferiorly by a veiled membrane, which serves as the
site of attachment of the fibers of the dilator tubae, or tensor veli palatini muscle (4,6,11).
The tubal lumen is shaped like two cones joined at their apexes. The juncture of the cones
is the narrowest point of the lumen and has been called the isthmus; its position usually is
described as at or near the juncture of the osseous and cartilaginous portions of the tube.
The lumen at this point is about 2 mm high and 1 mm wide (4). From the isthmus, the
lumen expands to about 8 to 10 mm in height and 1 to 2 mm in diameter at the
pharyngeal orifice. Tubal cartilage increases in mass from birth to puberty, and this
development has physiologic implications (12,13).
The cartilaginous eustachian tube does not follow a straight course in the adult but
extends along a curve from the junction of the osseous and cartilaginous portions to the
medial pterygoid plate, approximating the cranial base for the greater part of its course.
The eustachian tube crosses the superior border of the superior constrictor muscle
immediately posterior to its terminus within the nasopharynx. The thickened anterior
fibrous investment of the medial cartilage of the tube presses against the pharyngeal wall
to form a prominent fold, the torus tubarius, which measures 10 to 15 mm thick (4). The
torus is the site of origin of the salpingopalatine muscle and is the point of origin of the
salpingopharyngeal muscle, which lies within the inferoposteriorly directed
salpingopharyngeal fold (14).
The mucosal lining of the eustachian tube is continuous with that of the nasopharynx and
middle ear and is characterized as respiratory epithelium. Structural differentiation of this
mucosal lining is evident; mucous glands predominate at the nasopharyngeal orifice, and
there is graded change to a mixture of goblet, columnar, and ciliated cells near the
tympanum (15). The lining is folded, which provides greater surface area (16). Also,
mucosa-associated lymphoid tissue is present (17).
Eustachian Tube Muscles
Four muscles are associated with the eustachian tube: tensor veli palatini, levator veli
palatini, salpingopharyngeus, and tensor tympani (Fig. 88.2). Each has at one time or
another been directly or indirectly implicated in tubal function (4,18).
At rest the eustachian tube is closed; it opens during such actions as swallowing,
yawning, and sneezing and thereby permits the equalization of middle-ear and
atmospheric pressures. Although controversy still exists as to the mechanism of tubal
dilatation, most anatomic and physiologic evidence supports active dilatation induced
solely by the tensor veli palatini muscle (19,20 and 21), although Swarts and Rood (22)
provided some evidence that the levator veli palatini may have some function in opening
the anterior portion of the tube. Closure of the tube has been attributed to passive
reapproximation of tubal walls by extrinsic forces exerted by the surrounding deformed
tissues, by the recoil of elastic fibers within the tubal wall, or by both mechanisms. More
recent experimental and clinical data suggest that, at least for certain abnormal
populations, the closely applied internal pterygoid muscle may assist tubal closure by an
increase in its mass within the pterygoid fossa; this increase applies medial pressure to
the tensor veli palatini muscle and consequently to the lateral membranous wall of the
eustachian tube (21,23,24).
The tensor veli palatini muscle is composed of two fairly distinct bundles of muscle
fibers divided by a layer of fibroelastic tissue. The bundles lie mediolateral to the tube.
The more lateral bundle (the tensor veli palatini proper) is of an inverted triangular
design, taking its origin from the scaphoid fossa and the entire lateral osseous ridge of the
sulcus tubae for the course of the eustachian tube (Fig. 88.2A). The bundles descend
anteriorly, laterally, and inferiorly to converge in a tendon that rounds the hamular
process of the medial pterygoid lamina about an interposed bursa (Fig. 88.2B). This fiber
group then inserts into the posterior border of the horizontal process of the palatine bone
and into the palatine aponeurosis of the anterior portion of the velum (Fig. 88.3). The
more posteroinferior muscle fibers lack an osseous origin, extending instead into the
semicanal of the tensor tympani muscle. Here the latter group of muscle fibers receives a
second muscle slip, which originates from the tubal cartilages and sphenoid bone. These
muscle masses converge to a tendon that rounds the cochleariform process and inserts
into the manubrium of the malleus. This arrangement imposes a bipennate form to the
tensor tympani muscle (11). The tensor tympani does not appear to be involved in the
function of the eustachian tube.

FIGURE 88.3. Drawing shows the tensor veli palatini
muscle attachment along the lateral wall of the eustachian
tube, including its course around the hamulus of the
pterygoid bone and its attachment into the posterior
margin of the hard palate. EAC, external auditory canal.
(Redrawn from Bluestone CD, Klein JO. Otitis media,
atelectasis, and eustachian tube dysfunction. In:
Bluestone CD, Stool SE, Kenna MA, eds. Pediatric
otolaryngology, 3rd ed. Philadelphia: WB Saunders, 1996:405.)



The medial bundle of the tensor veli palatini muscle lies immediately adjacent to the
lateral membranous wall of the eustachian tube and is called the dilator tubae muscle
(11). It takes its superior origin from the posterior third of the lateral membranous wall of
the eustachian tube. The fibers descend sharply to enter and blend with the fibers of the
lateral bundle of the tensor veli palatini muscle. This inner bundle is responsible for
active dilatation of the tube by inferolateral displacement of the membranous wall
(11,18,24).
Levator veli palatini muscle arises from the inferior aspect of the petrous apex and from
the lower border of the medial lamina of the tubal cartilage. The fibers pass
inferomedially, paralleling the tubal cartilage and lying within the vault of the tubal floor.
They fan out and blend with the dorsal surface of the soft palate (8,18). Most
investigators deny a tubal origin for this muscle and believe that it is related to the tube
only by loose connective tissue. The levator is not the primary dilator of the tube but
probably adds to its support and contributes to its function by elevating the medial arm of
the cartilage at the nasopharyngeal end of the eustachian tube (25).
Salpingopharyngeal muscle arises from the medial and inferior borders of the tubal
cartilage via slips of muscular and tendinous fibers (Fig. 88.2A). The muscle then courses
inferoposteriorly to blend with the mass of the palatopharyngeal muscle (18). Rosen (14)
examined 10 hemisected human heads and identified the muscle in nine specimens;
however, in all cases, the muscle fibers were few and appeared to lack any ability to
perform physiologically.
Infant Versus Adult Anatomy
It is likely that differences in the anatomy of the infant compared with the adult are
related, in part, to the increased incidence of otitis media in the pediatric age group.
These anatomic differences have been described only recently. The eustachian tube in the
infant is about 50% as long as that in the adult; its length averages about 18 mm. The
cartilaginous tube represents somewhat less than two thirds of this distance, whereas the
osseous portion is relatively longer and wider in diameter than in the adult. The height of
the pharyngeal orifice of the infant eustachian tube is about half that of the adult, but the
width is similar. The ostium of the tube is more exposed in the infant than it is in the
adult because it lies lower in the shallower nasopharyngeal vault. The direction of the
tube varies from horizontal to an angle of about 10 degrees to the horizontal, and the tube
is not angulated at the isthmus but merely narrows (8). Holborow (26) demonstrated that
in infants the medial cartilaginous lamina is relatively shorter because there is less tubal
mass and stiffness in the infant tube than in that of the older child and adult. The tensor
veli palatini muscle is less efficient in the infant.
The eustachian tube lengthens rapidly during early childhood, essentially reaching its
adult size by 7 years of age (27). Ishijima and colleagues found the length of the lumen of
the infant tube to be 21 mm compared with the 37 mm average length of an adult's (28).
The effect of these changes on efficiency of eustachian tube function has yet to be
determined, but age-related changes in eustachian tube function suggest more efficient
muscular activity and a system that is less likely to act as a passive conduit for nasal
secretions. In infants, the eustachian tube is about half as long as that in the adult (27); it
averages about 18 mm. The cartilaginous tube represents somewhat less than two thirds
of this distance, whereas the osseous portion is relatively longer and wider in diameter
than it is in the adult. The height of the pharyngeal orifice of the infant eustachian tube is
about one half that of the adult, but the width is similar. The ostium of the tube is more
exposed in the infant than in the adult: it lies lower in the shallower nasopharyngeal vault.
The direction of the tube varies from horizontal to an angle of about 10 degrees to the
horizontal, and the tube is not angulated at the isthmus but merely narrows (8); in the
adult, the tube is approximately 45 degrees related to the horizontal plane (4). Holborow
(26) demonstrated that the medial cartilaginous lamina is relatively shorter in infants.
Cartilage mass increases from birth to puberty (12). The density of elastin in the cartilage
is less in the infant (29), but the cartilage cell density is greater (30). The volume of
Ostmann's fat pad is less in the infant, but the width is similar in the two age groups (31).
The angular relationship between the tensor veli palatini muscle and the cartilage varies
in the infant but is relatively stable in the adult (32). Table 88.1 summarizes the
differences between the anatomy of the eustachian tube in the infant as compared with
the adult.

TABLE 88.1. DEVELOPMENTAL DIFFERENCES
BETWEEN ANATOMY OF EUSTACHIAN TUBE
IN INFANTS COMPARED TO ADULTS



Some or possibly all these developmental differences between the infant and the adult
most likely are related to the relatively less efficient active tubal opening mechanism in
the infant and young child, which would make this age group susceptible to middle-ear
disease. Because the infant (and young child) has a shorter eustachian tube than the older
child and adult, nasopharyngeal secretions can reflux more readily into the middle ear
through the shorter tube and result in otitis media.
PHYSIOLOGY OF THE EUSTACHIAN TUBE
The eustachian tube has at least three physiologic functions with respect to the middle ear
(Fig. 88.4): (a) pressure regulation (i.e., ventilation) of the middle ear to equilibrate gas
pressure in the middle ear with atmospheric pressure; (b) protection from nasopharyngeal
sound pressure and secretions; and (c) clearance of secretions produced within the middle
ear into the nasopharynx. Even though the pressure regulation function is the most
important of these functions, the protective, drainage, and clearance functions are
reviewed so that the reader will be better able to visualize and understand the pressure
regulation function. The term pressure regulation is more accurate than ventilation,
because the middle ear is a pressure-regulated cavity and not continuously ventilated. In
the following discussion, fluid flow through the tube includes gas (airflow) and liquid
flow.

FIGURE 88.4. Three physiologic functions of the
eustachian tube in relation to the middle ear. NP,
nasopharynx; ET, eustachian tube; TVP, tensor veli
palatini muscle; ME, middle ear; TM, tympanic
membrane; EC, external canal; EAC, external auditory
canal. (Redrawn from Bluestone CD, Klein JO. Otitis
media, atelectasis, and eustachian tube dysfunction. In:
Bluestone CD, Stool SE, eds. Pediatric otolaryngology,
2nd ed. Philadelphia: WB Saunders, 1990:320.)



Clearance of secretions from the middle ear is provided by the mucociliary system of the
eustachian tube and some of the middle-ear mucous membrane. In ideal tubal function,
intermittent active opening of the eustachian tube, which results only from contraction of
the tensor veli palatini muscle during swallowing, maintains nearly ambient pressures in
the middle ear (19,20). Assessment of these functions has been helpful in understanding
the physiology and pathophysiology of eusta-chian tube function as well as in the
diagnosis and management of patients with middle-ear disease (36).
Protective and Clearance Functions
In the past, clearance and drainage functions of the eustachian tube have been assessed by
a variety of methods. Radiographic techniques have been used to assess the flow of
contrast media from the middle ear (tympanic membrane not intact) into the nasopharynx
(37,38,39,40,41 and 42). Bauer (43) assessed clearance by observing methylene blue in
the pharynx after it had been instilled into the middle ear. Elbrnd and Larsen (44)
assessed middle eareustachian tube mucociliary flow by determining the time that
elapsed after saccharin had been placed on the mucous membrane of the middle ear until
the subject reported tasting it. Unfortunately, all these methods are qualitative and
actually test eustachian tube patency rather than measure the clearance function of the
tube quantitatively. Even though abnormalities of the protective function are directly
related to the pathogenesis of otitis media, this function has only been assessed by
radiographic techniques by a test that was a modification of a tubal patency test described
by Wittenborg and Neuhauser (39,40, and 41,45).
Model of Protective and Clearance Functions
The eustachian tube, middle ear, and mastoid air cell system can be likened to a flask
with a long, narrow neck (Fig. 88.5). The mouth of the flask represents the
nasopharyngeal end; the narrow neck, the isthmus of the eustachian tube; and the bulbous
portion, the middle ear and mastoid air chamber. Fluid flow through the neck depends on
the pressure at either end, the radius and length of the neck, and the viscosity of the
liquid. When a small amount of liquid is instilled into the mouth of the flask, liquid flow
stops somewhere in the narrow neck owing to capillarity within the neck and the relative
positive air pressure that develops in the chamber of the flask. This basic geometric
design is considered critical for the protective function of the eustachian tubemiddle ear
system. Reflux of liquid into the body of the flask occurs if the neck is excessively wide;
this is analogous to an abnormally patent human eustachian tube in which there is not
only free flow of air from the nasopharynx into the middle ear but also free flow of
nasopharyngeal secretions, which can result in reflux otitis media. This is analogous to
the patulous eustachian tube (46,47). Figure 88.6 shows that a flask with a short neck
would not be as protective as a flask with a long neck (48). As described, infants
anatomically have a shorter eustachian tube than adults, which would make reflux more
likely to occur in the infant. The position of the flask in relation to the liquid is another
important factor. In humans, the supine position enhances flow of liquid into the middle
ear; thus, infants might be at particular risk for developing reflux otitis media because
they are frequently supine.

FIGURE 88.5. Flask model of eustachian tubemiddle
earmastoid air cell system in which the mouth of the
flask represents the nasopharyngeal end of the eustachian
tube, the neck is the cartilaginous portion of the tube, and
the bulbous portion represents the middle ear and mastoid
air cells. (Redrawn from Bluestone CD, Klein JO. Otitis
media, atelectasis, and eustachian tube dysfunction. In:
Bluestone CD, Stool SE, Kenna MA, eds. Pediatric
otolaryngology, 3rd ed. Philadelphia: WB Saunders, 1996:417.)



FIGURE 88.6. Flask model used to show how the shorter
length of the eustachian tube can adversely affect the
protective function in the child, compared with that in the
adult. (Redrawn after Bluestone CD, Klein JO. Otitis
media, atelectasis, and eustachian tube dysfunction. In:
Bluestone CD, Stool SE, Kenna MA, eds. Pediatric
otolaryngology, 3rd ed. Philadelphia: WB Saunders,
1996:417.)



Reflux of a liquid into the vessel also can occur if a hole is made in the bulbous portion
of the flask (Fig. 88.7A and Fig. 88.7B) because to do so prevents the creation of the
slight positive pressure in the bottom of the flask that deters reflux; that is, in this
situation, the middle ear and mastoid physiologic cushion of air is lost. This hole is
analogous to a perforation of the tympanic membrane or the presence of a tympanostomy
tube that could allow reflux of nasopharyngeal secretions as a result of the loss of the
middle earmastoid air cushion. Similarly, following a radical mastoidectomy, a patent
eustachian tube could cause troublesome otorrhea (49).

FIGURE 88.7. Fluid flow into a flask as a model for
eustachian tubemiddle ear function. A: Normal function.
B: Effect of perforation. C: Effect of negative pressure
on the bottom of the flask. D: Effect of positive pressure
on the mouth of the flask. (Redrawn from Bluestone CD,
Klein JO. Otitis media, atelectasis, and eustachian tube
dysfunction. In: Bluestone CD, Stool SE, Kenna MA,
eds. Pediatric otolaryngology, 3rd ed. Philadelphia: WB
Saunders, 1996:417.)



If negative pressure is applied to the bottom of the flask, the liquid is aspirated into the
vessel (Fig. 88.7A and Fig. 88.7C). In the clinical situation represented by the model,
high negative middle-ear air pressure could lead to the aspiration of nasopharyngeal
secretions into the middle ear. If positive pressure is applied to the mouth of the flask, the
liquid is insufflated into the vessel (Fig. 88.7A and Fig. 88.7D). Nose blowing, crying,
closed-nose swallowing, diving, or descent in an airplane could create high positive
nasopharyngeal pressure and result in a similar condition in the human system.
One of the major differences between a flask with a rigid neck and a biologic structure
such as the eustachian tube is that the isthmus (neck) of the human tube is compliant.
Application of positive pressure at the mouth of a flask with a compliant neck distends
the neck, enhancing fluid flow into the vessel. Thus, less positive pressure is required to
insufflate liquid into the vessel. In humans, insufflation of nasopharyngeal secretions into
the middle ear occurs more readily if the eustachian tube is abnormally distensible (i.e., it
has increased compliance). When negative pressure is applied in a flask with a compliant
neck, liquid flow through the neck does not occur until a negative pressure is slowly
applied to the bottom of the flask. In this case, fluid flow occurs even if the neck is
collapsed. If the negative pressure is applied suddenly, however, temporary locking of the
compliant neck prevents flow of the liquid. Therefore, the speed with which the negative
pressure is applied and the compliance in such a system appear to be critical factors in the
results.
Clinically, aspiration of gas into the middle ear is possible because negative middle-ear
pressure develops slowly as gas is absorbed by the middle-ear mucous membrane. On the
other hand, sudden application of negative middle-ear pressure such as occurs with rapid
alterations in atmospheric pressure (as in the descent in an airplane, in a descent after
diving, and during an attempt to test the ventilatory function of the eustachian tube) could
lock the tube, thus preventing the flow of air.
Certain aspects of fluid flow from the middle ear into the nasopharynx can be
demonstrated by inverting the flask of the model. In this case, the liquid trapped in the
bulbous portion of the flask does not flow out of the vessel because of the relative
negative pressure that develops inside the chamber. If a hole is made in the vessel,
however, the liquid drains out of the flask because the suction is broken. Clinically, these
conditions occur in cases of middle-ear effusion; pressure is relieved by spontaneous
rupture of the tympanic membrane or by myringotomy. Inflation of air into the flask
could also relieve the pressure, which may explain the success of the Politzer or Valsalva
method in clearing a middle-ear effusion resulting from barotrauma.
The examples of fluid flow through a flask present some of the mechanical aspects of the
physiology of the human middle-ear system. Other factors that can affect flow of liquid
and air through the middle ear are (a) the mucociliary transport system of the eustachian
tube and middle ear (clearance); (b) active tubal opening and closing, acting to pump
liquid out of the middle ear (43); and (c) surface tension factors.
The clearance function has been studied by insertion of foreign material into the middle
ear of animal models (50). Such material flows toward the middle-ear portion of the
eustachian tube. This movement is related to ciliary activity that occurs in the eustachian
tube and parts of the middle ear; these ciliated cells in the middle ear are increasingly
more active as their location becomes more distal to the opening of the eustachian tube.
In a series of elegant experiments by Honjo (42), the eustachian tube was shown to
pump liquid out of the middle ear in both animal models and humans. When negative
pressure was present within the middle ear, however, this function was impaired.
Several investigators have determined certain surface tension factors that could be
involved with normal eustachian tube function. Birkin and Brookler (51) isolated surface
tensionlowering substances from washings of eustachian tubes of dogs and postulated
that these substances could act to enhance eustachian tube functions, similar to surfactant
in the lung. Rapport and colleagues (52) described a similar substance and demonstrated
the effect of washing out the eustachian tube on the opening pressure in the experimental
animal; others also demonstrated a surfactant-like phospholipid in the middle ear and
eustachian tube of animals and humans (53,54). In a study in gerbils, Fornadley and
Burns (55) produced middle-ear effusions by injecting killed Streptococcus pneumoniae
into the middle ear through the tympanic membrane, which increased the opening
pressure of the eustachian tube. When the investigators introduced exogenous surfactant,
the opening pressure decreased. Another investigation showed that middle-ear negative
pressure can reduce clearance (56). Recently, Bunne and colleagues (57) postulated that
mucoadhesive forces may be involved in not only middle-ear disease, but also following
middle-ear aeration with tympanostomy tube placement. From these studies, it is
apparent that the clearance function of the eustachian tubemiddle ear system is
important in maintaining a healthy middle ear. Because otitis media is so common in
humans, efficient removal of middle-ear effusions must depend, to a large extent, on
these functions.
Pressure Regulation Function
From studies in children, the function of the eustachian tube has been postulated (49).
The normal eustachian tube is functionally obstructed or collapsed at rest; there is
probably a slight negative pressure in the middle ear. When the eustachian tube functions
ideally, intermittent active dilatation (opening) of the tube maintains near-ambient
pressures in the middle ear. Under physiologic conditions, the fluctuations in ambient
pressure are bidirectional (i.e., either to or from the middle ear), relatively small in
magnitude, and not readily appreciated (58). These fluctuations reflect the increase and
decrease in barometric pressures associated with changing weather conditions and
elevation or both; however, the changes in middle-ear pressure show mass directionality,
can achieve appreciable magnitudes, and can result in pathologic changes. A major
reason for these conditions is that the middle ear is a relatively rigid (i.e., noncollapsible)
gas pocket surrounded by mucous membrane in which gases are exchanged between the
middle-ear space and the mucosa (59). Differential pressure exceeds 54 mm Hg between
the middle-ear space at atmospheric pressure and the microcirculation in the mucous
membrane. This represents a diffusion-driven gradient from the middle-ear cavity to the
mucosa that can produce an underpressure (relative to ambient pressure) in the middle ear
of more than 600 mm H
2
O during equilibration. Doyle and co-workers (60), in
experiments in primates, demonstrated that oxygen (O
2
) and carbon dioxide (CO
2
)
exchange is diffusion limited, whereas nitrogen (N
2
) is perfusion limited. Some
investigators have postulated that gases can pass to and from the middle ear through the
tympanic membrane, but Doyle and co-investigators (61) showed in animal experiments
that there is no O
2
and CO
2
trans-tympanic membrane exchange from the external ear
canal into the middle ear; exchange of N
2
occurs, but not at physiologic rates.
In an effort to describe normal eustachian tube function by using the microflow technique
inside a pressure chamber, Elner and co-workers (62) studied 102 adults with intact
tympanic membranes and apparently no history of otologic disorder. The patients were
divided into four groups according to their abilities to equilibrate static relative positive
and negative pressures of 100 mm H
2
O in the middle ear. The patients in group 1 were
able to equilibrate pressure differences across the tympanic membrane completely. Those
in group 2 equilibrated positive pressure, but a small residual negative pressure remained
in the middle ear. Subjects in group 3 were capable of equilibrating only relative positive
pressure with a small residual pressure remaining but not negative pressure. Patients in
group 4 were incapable of equilibrating any pressure. These data probably indicate
decreased stiffness of the eustachian tube in the subjects in groups 2 to 4 compared with
those in group 1. This study also showed that 95% of normal adults could equilibrate an
applied positive pressure and that 93% could equilibrate applied negative pressure to
some extent by active swallowing; however, 28% of the subjects could not completely
equilibrate either applied positive or negative pressure or both.
Children have less efficient eustachian tube ventilatory function than adults. Bylander
(63) compared the eustachian tube function of 53 children with that of 55 adults, all of
whom had intact tympanic membranes and who were apparently otologically healthy.
Using a pressure chamber, Bylander and Tjernstrom (64) reported that 35.8% of the
children could not equil-ibrate applied negative intratympanic pressure (100 mm H
2
O)
by swallowing, whereas only 5% of the adults were unable to perform this function.
Children 3 to 6 years of age had worse function than those 7 to 12 years of age. In this
study and a subsequent one conducted by the same research group, children who had
tympanometric evidence of negative pressure within the middle ear had poor eustachian
tube function (64). From these two studies, it can be concluded that even in apparently
otologically normal children, eustachian tube function is not as good as in adults;
therefore, the higher incidence of middle-ear disease in children can be attributed to this
finding.
Many children without apparent middle-ear disease have high negative middle-ear
pressure. In children, however, eu-stachian tube function does improve with advancing
age, which is consistent with the decreasing incidence of otitis media from infancy to
adolescence.
Another explanation for the finding of high negative middle-ear pressure in children is
the possibility that some people who are habitual sniffers actually create underpressure
within the middle ear by this act (65). This mechanism is uncommon in children,
however.
In studying the measurement of middle-ear pressure, Brooks (66) determined by
tympanometry that the resting middle-ear pressure in a large group of apparently normal
children was between 0 and 175 mm H
2
O; however, pressures outside this range have
been reported as normal for large populations of apparently asymptomatic children who
were measured for middle-ear pressure by screening. High negative middle-ear pressure
does not necessarily indicate disease; it may indicate only physiologic tubal obstruction.
Ventilation occurs but only after the nasopharynxmiddle ear pressure gradient reaches
an opening pressure. It has been suggested that these children probably should be
considered at risk for middle-ear problems until more is learned about the normal and
abnormal physiology of the eustachian tube (67). In normal adults, Alberti and Kristensen
(68) obtained resting middle-ear pressures of 50 to 50 mm H
2
O. Again, a pressure
outside this range does not necessarily mean that the patient has ear disease; however,
high negative pressure within the middle ear can result in middle-ear effusion (69).
The rate of gas absorption from the middle ear has been reported by several investigators
to be about 1 mL in a 24-hour period (70). However, because values taken over a short
period were extrapolated to arrive at this figure, the true rate of gas absorption over 24
hours has yet to be determined in humans.
In a study by Cantekin and co-workers (71), serial tympanograms were obtained in rhesus
monkeys to determine the gas absorption process. During a 4-hour observation period,
the middle-ear pressure was approximately normal in alert animals, whereas when the
animals were anesthetized and swallowing was absent, the middle-ear pressure decreased
to 60 mm H
2
O and remained at that level. The experiment indicated that normally
middle-ear gases are nearly in equilibrium with the mucosal blood-tissue gases or inner-
ear gas pressures.
Under these circumstances, the gas absorption rate is small because the partial pressure
gradients are not great. In the normally functioning eustachian tube, the frequent
openings of the tube readily equilibrate the pressure differences between the middle ear
and the nasopharynx with a small volume of air entering into the middle ear; however, an
abnormally functioning eustachian tube may alter this mechanism (72,73 and 74).
Grntved and colleagues (75) measured the gas tension in the middle ears of 26 adults
who were otologically healthy, using a gas chromatographic technique. They reported
CO
2
(median 52 mm Hg) and N
2
(median 605 mm Hg) to be relatively stable, but values
for O
2
fluctuated more (median 54 mm Hg; range 73 to 111 mm Hg). Thus, the normal
middle ear has lower O
2
levels and higher N
2
levels than room air but probably similar to
that of venous blood (76). Shupak and associates (77) reported that middle-ear O
2
and
CO
2
tensions affect the pressure regulation system, most likely through a feedback loop
between the middle ear chemoreceptors and the brainstem. Thus, pressure is not regulated
only by the differential between middle-ear and ambient pressures.

HIGHLIGHTS
The eustachian tube is not in anatomic isolation but is part of a
system made up of the nose, nasopharynx, middle ear, and
mastoid, in addition to the tube. In reality, the eustachian tube is
not just a tube but an organ.
The eustachian tube is shorter in the infant and young child
compared with that in the older child, adolescent, and adult,
which would make the shorter tube less protective from
nasopharyngeal secretions.
The cartilaginous portion of the eustachian tube is closed at rest
in the physiologic condition, whereas the osseous portion is
open at all times.
The eustachian tube is lined with respiratory epithelium.
The tensor veli palatini muscle is the primary muscle that
actively opens the eustachian tube and is functionally
significant.
The tensor veli palatini has two fairly distinct bundles. The
posteroinferior bundle extends to form the tensor tympani
muscle, but that muscle does not have any known role in
eustachian tube function.
The eustachian tube has the following functions in relation to
the middle ear: pressure regulation, protection, and clearance.
In the healthy state, the middle ear and mastoid are protected
from unwanted nasopharyngeal secretions by the anatomy of
the eustachian tube system and by the middle-ear gas cushion.
Liquid flow from the nasopharynx, such as unwanted
nasopharyngeal secretions, is enhanced by a tympanic
membrane that is not intact, because the middle-ear air cushion
is altered. The middle-ear gas composition is not identical to
that of room air; O
2
is lower and CO
2
and N
2
levels are higher.
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34. Suzuki C, Balaban C, Sando I, et al. Postnatal development of eustachian tube: a computer-aided
3-D reconstruction and measurement study. Acta Otolaryngol (Stockh) 1998;118:837843.
35. Sudo M, Sando I. Developmental changes in folding of the human eustachian tube. Acta
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36. Bluestone CD, Klein JO. Otitis media in infants and children, 3rd ed. Philadelphia: WB Saunders
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37. Aschan GK. The anatomy of the eustachian tube with regard to its function. Acta Soc Med
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38. Compere WE Jr. The radiologic evaluation of eustachian tube function. Arch Otolaryngol
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41. Bluestone CD, Wittel RA, Paradise JL, et al. Eustachian tube function as related to adenoidectomy
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42. Honjo I. Experimental study of the pumping function of the eustachian tube. Acta Otolaryngol
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43. Bauer F. Tubal function in the glue ear: urea for glue ears. J Laryngol Otol 1975;89:6371.
44. Elbrnd O, Larsen E. Mucociliary function of the eustachian tube. Arch Otolaryngol
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47. Continuous long-term measurements of the middle-ear pressure in subjects with symptoms of
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48. Bluestone CD. Current concepts in eustachian tube function related to otitis media. Auris Nasus
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50. Albiin N, Hellstrm S, Stenfors L-E. Clearance of effusion material from the attic spaceCan
experimental study in the rat. Int J Pediatr Otorhinolaryngol 1983;5:110.
51. Birkin EA, Brookler KH. Surface tension lowering substance of the canine eustachian tube. Ann
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53. Hagen WE. Surface tension lowering substance in eustachian tube function. Laryngoscope
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54. Karchev T, Watanabe N, Fujiyoshi T, et al. Surfactant-producing epithelium in the dorsal part of
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55. Fornadley JA, Burns JK. The effect of surfactant on eustachian tube function in a gerbil model of
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56. Takahashi H, Honjo I, Hayashi M, et al. Clearance function of eustachian tube and negative
middle-ear pressure. Ann Otol Rhinol Laryngol 1992;101:759762.
57. Bunne M, Falk B, Hellstrom S, et al. Variability of eustachian tube function in children with
secretory otitis media. Evaluations at tube insertion and at follow-up. Int J Pediatr
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58. Doyle WJ, Seroky JT. Middle-ear gas exchange in rhesus monkeys. Ann Otol Rhinol Laryngol
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59. Alper CM, Karnavas WJ, Swarts JD, et al. Middle-ear gas composition of cynomolgus monkeys:
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estimation of exchange rate. Arch Otolaryngol Head Neck Surg 1995;121:887892.
61. Doyle WJ, Alper CM, Seroky JT, et al. Exchange rates of gases across the tympanic membrane in
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64. Bylander A, Tjernstrom O. Changes in eustachian tube function with age in children with normal
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65. Falk B, Magnuson B. Eustachian tube closing failure in children with persistent middle-ear
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66. Brooks DN. The use of the electroacoustic impedance bridge in the assessment of middle-ear
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67. Bluestone CD, Beery QC, Paradise JL. Audiometry and tympanom-etry in relation to middle-ear
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68. Alberti PW, Kristensen R. The clinical application of impedance audiometry: a preliminary
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on eustachian tube ventilatory function. Laryngoscope 1996;106:221224.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

89 OTITIS MEDIA WITH EFFUSION
Head & Neck SurgeryOtolaryngology
89




OTITIS MEDIA WITH EFFUSION
MARGARET A. KENNA
REZA RAHBAR

M.A. Kenna and R. Rahbar: Department of Otolaryngology, Children's Hospital, Boston, Massachusetts.


Definitions and Terminology
Epidemiology
Risk Factors for Middle-Ear Disease
Pathophysiology
Microbiology
Evaluation
History
Physical Examination
Hearing Evaluation
Treatment and Prevention
Medical Management: Antimicrobial Agents
Prevention
Surgical Therapy: Myringotomy and Tube Insertion
Adenoidectomy and Tonsillectomy
Complications
Summary
Chapter References
Otitis media (OM) is the most common disease, with the exception of upper respiratory
infections (URIs), for which a child visits the pediatrician, and is a not infrequent
diagnosis in adults (1). Although the diagnosis and the treatment of OM have improved,
serious complications still occur (2). However, nonlife-threatening complications such
as conductive hearing loss are common, causing difficulty for many children and
sparking controversy about the importance and management of such complications (2).
DEFINITIONS AND TERMINOLOGY
Otitis media represents an inflammatory condition of the middle ear and mastoid space,
without reference to etiology or pathogenesis (3). Numerous terms and classifications
have been used to define the various inflammatory processes related to OM. The current
terminology is based on knowledge of the pathogenesis of OM as well as the etiology and
clinical course. The presence or absence of middle-ear effusion (MEE) and its duration
help further define the process. Effusion is the liquid resulting from infection and
mucosal inflammation and can occur in all areas of the pneumatized temporal bone.
Effusion may be serous (thin, watery), mucoid (thick, viscous), or purulent (pus). The
temporal sequence of the process may be described as acute (0 to 3 weeks in duration),
subacute (3 to 12 weeks in duration), or chronic (greater than 12 weeks in duration).
Unless the patient's previous middle-ear status is known to the examiner, duration of the
disease can be very difficult to determine. Tympanograms and audiograms obtained
previously can often help to further define the duration.
Acute otitis media (AOM) is characterized by a rapid onset of infection of the middle ear.
Symptoms include fever, irritability, otalgia, and hearing loss. Recurrent AOM indicates
four or more episodes of AOM in 1 year or three or more episodes in a 6-month period.
Otitis media with effusion (OME) indicates the presence of effusion behind an intact
tympanic membrane (TM), usually resulting in conductive hearing loss but without any
signs of acute inflammation. In some cases of OME, an air-fluid level may be observed
through a translucent TM. Chronic suppurative otitis media (CSOM) is characterized by
persistence of purulent otorrhea through a TM perforation or tympanostomy tube. Further
description of the TM (intact, perforated, tympanostomy tube present, retracted,
atelectatic, or presence of tympanosclerosis) will help more clearly define the type of OM
(3).
EPIDEMIOLOGY
The epidemiology of OM has been well studied (4,5 and 6). The onset of AOM during
the first year of life is important because the majority of children with multiple
recurrences of AOM have their first episode before the age of 12 months (3,4). If a child
has not had OM before the age of 3 years, he is statistically unlikely to develop severe or
recurrent OM. The Greater Boston Otitis Media Study Group followed 2,565 children for
several years and found that 93.4% of these children developed one or more episodes of
AOM by age 7. In this study, 13% of children had at least one episode of OM by 3
months of age, 46% had three or more episodes of AOM by 3 years of age, and 75% had
three or more episodes by 7 years of age (4). Overall the highest incidence of AOM for
both sexes was in the 6- to 11-month age group (2,4,6).
Several investigators have shown a high incidence of persistent MEE after an episode of
AOM (4,6) (Fig. 89.1). The mean duration of OME after AOM in several studies is
approximately 40 days (4,7). In one group, younger children were noted to have slower
resolution of MEE following AOM than did older children (4). Investigations involving
healthy children have revealed a high incidence of asymptomatic OME (3,6). The
incidence of OME appears to peak during the second year of life, is most prevalent
during the winter months, and is associated with URIs. In a study of children 2 to 6 years
of age, it was found that 53% of children during the first year of the study and 61%
during the second year developed OME in at least one ear (6). Teele et al. found that the
mean time with fluid in the middle ear was about 1 month in each of the first 2 years of
life and in a few children included more than half the time during the first year (6). More
recently, Paradise and colleagues found a cumulative proportion of days with MEE of
20.4% for the first year of life and 16.6% for the second year (8). During the first 2 years
of life, both AOM and OME are more commonly bilateral, becoming more frequently
unilateral with increasing age. Most children have resolution of asymptomatic MEE
within a few months without medical or surgical intervention (6).

FIGURE 89.1. Duration of effusion after first episode of
acute otitis media. [Adapted from Teele DW, Klein JO,
Rosner BA. Epidemiology of otitis media in children.
Ann Otol Rhinol Laryngol 1980;89(suppl 68):5].



In some studies the incidence of AOM is similar between boys and girls. However,
several other studies have shown a higher incidence in boys than girls (3). Past studies
have suggested that American white and Hispanic children have a higher incidence of
middle-ear infections than American black children (3). However, Casselbrant and
colleagues and Paradise et al. found that black children had at least as much middle-ear
disease as white children who received equivalent care (8,9). A very high incidence of
middle-ear infections has been reported in Native Americans and Eskimos, even when
there is excellent access to medical care (3,10). African and Australian aboriginal
children also have severe middle-ear disease, manifesting as necrotizing OM, chronic
otorrhea, large TM perforations, ossicular damage, and hearing impairment (3).
In the Boston study there was an increased incidence of AOM in children with a sibling
history of recurrent OM. Additionally, Casselbrant and colleagues showed a strong
genetic predisposition to OM, with a higher incidence of OM in children who have
siblings or parents with a significant history of OM (11). Children who live in crowded
households or low socio-economic conditions and/or who have poor medical care also
have been found to have an increased incidence of both acute and chronic OM. These
factors are not definitive in all studies, however, and may simply reflect increased
exposure to many other children with URIs. In addition, the relationship between
attending day care and an increased incidence of OM in children is well established.
Wald and colleagues reported an increased incidence of OM as a complication of URIs in
children attending group care and day care, as opposed to home care, from birth to 3
years of age (12). However, the risk of OM was similar for all children regardless of their
care situation after 3 years of age. Many other investigators have substantiated these
results (3,13). Contributing factors for this increased incidence include exposure to large
numbers of other children (with a concomitant increased exposure to URIs), decreased
breast-feeding, and exposure to second-hand smoke. Increased parental awareness of
illness with earlier and more frequent otologic examinations in an effort to decrease
parental leave time from work also has contributed to the documentation of the increase.
Seasonal variation in the incidence of OM also has been reported, most commonly in
winter, fall, and spring (3,4). In one study, 51% of children had an episode of OM in the
winter, 48% in the spring and fall, and 27% in the summer (5). All studies have shown
that there is a correlation between the frequency of URI and incidence of OM, and MEE
that is associated with URI in the winter months lasts longer than in the summer (3,6).
RISK FACTORS FOR MIDDLE-EAR DISEASE
Many medical or anatomic abnormalities have been noted to increase the risk of middle-
ear disease. Craniofacial anomalies affecting eustachian tube (ET) function often increase
the risk of OM. Children with a cleft palate or deformity of the mid-face, skull base, or
nose/paranasal sinuses have a statistically higher incidence of OM at all ages, especially
during the first 2 years of life (3,14). Although some studies have shown that the
incidence of middle-ear disease decreases after surgical repair of cleft palate, many
children with a cleft palate continue to have middle-ear problems long after the palate
repair. Other craniofacial disorders associated with an increase risk of OM include Down
syndrome, Apert syndrome, and the mucopolysaccharidoses (3).
Children with congenital or acquired immunodeficiency are at a higher risk of many
types of infection, including middle-ear disease. Conditions such as
hypogammaglobulinemia, IgA deficiency, DiGeorge syndrome, human
immunodeficiency virus (HIV) disease, and drug-induced immunodeficiency
(chemotherapy, steroids) often lead to an immune system unable to elicit an adequate
response to infections. Infants and very young children have immune systems that are
immature compared with older children and adults, and this appears to make them more
susceptible to OM in some cases.
Other conditions associated with an increased incidence of OM are allergy, nasal
obstruction (sinusitis, adenoid hypertrophy, nasal/nasopharyngeal tumors), ciliary
dysfunction, and prolonged nasal intubation or nasogastric tube placement (3,15). A role
for allergy in the etiology of OM has long been postulated (Fig. 89.2). The allergic
response can predispose patients to MEE by obstructing and congesting the ET. Many
patients with OM have concomitant allergic rhinitis or asthma. A history of one or more
major allergic illnesses in parents of children with OM is frequently present. Elevated
immunoglobulin E (IgE) levels in the middle ear and serum of some children with OM
have been identified, and mast cells are found in middle-ear mucosa. Conversely, OM is
most common in the winter and early spring; the major allergens that cause acute nasal
allergy (grasses, trees, pollens) are found in late spring and early fall. Most studies reveal
an absence of eosinophils and few or no IgE-producing cells in middle-ear mucosa and
MEE. Most patients do not have marked improvement of their ear disease even with
aggressive allergic management, even though nasal and other symptoms may be
markedly improved. In summary, there are many patients with OM, many patients with
allergy, and some with both. It seems very reasonable that in some patients the allergic
response plays a role in mediating or continuing the episode of OM (16).

FIGURE 89.2. Factors involved in the etiology and
pathogenesis of otitis media. (From Bluestone CD, Klein
JO. Otitis media, atelectasis, and eustachian tube
dysfunction. In: Bluestone CD, Stool SE, Kenna MA,
eds. Pediatric otolaryngology, 3rd ed. Philadelphia: WB
Saunders, 1996:388.)



Most children with recurrent or persistent OM have intact immune systems. However, if
the middle-ear infections are especially severe or associated with recurrent sinusitis,
bronchitis, or gastrointestinal problems, immunologic abnormalities may be present. The
middle-ear mucosa has a secretory immune system very similar to the rest of the
respiratory tract. Middle-ear effusion that results from acute or chronic infection contains
immunoglobulin (IgA, IgG, IgM, IgD), immune complexes, and chemical mediators
involved in the inflammatory response. Possible humoral immune deficiencies in children
with OM include IgA, IgG (especially of IgG subclasses 2 and 3), and complement
deficiency (3). Otitis media also may be one of the multiple infectious complications seen
in the presence of HIV disease, together with defects of chemotaxis, phagocytosis
(neutropenia), or killing (chronic granulomatous disease). In comparing otitis-prone
children with those who have only occasional episodes of OM, Prellner and Kalm (17)
noted a decreased ability of the OM-prone children to produce antibodies against AOM-
associated antigens and that these children also may have delayed B-cell maturation.
PATHOPHYSIOLOGY
Abnormal function of the ET is the cornerstone of the pathogenesis of OM. The ET in
infants and children is shorter, more horizontal, and functionally less mature compared
with adults. Conditions such as URIs lead to edema and congestion of respiratory mucosa
of the ET and middle ear, causing narrowing of the ET lumen. This leads to an increase
in negative middle-ear pressure, causing an influx of bacteria and viruses from the
nasopharynx when the ET opens. The bacteria and viruses in the middle ear then elicit an
inflammatory response (3). The acute inflammatory response includes mucosal edema,
capillary engorgement, and infiltration of polymorphonuclear leukocytes into the middle-
ear space. As the inflammatory response becomes chronic, there is infiltration of
lymphocytes, proliferation of the mucosal lamina propria, enzymatic destruction of
bones, and granulation tissue formation, worsening the obstruction and ventilation of
middle ear and ET (18).
Many other confounding variables affecting ET function include patulous or
functionally/anatomically obstructed tubes, and abnormalities of the respiratory mucosa,
including allergy, immunocompromise, and ciliary dysfunction (Fig. 89.2). Allergy has
long been implicated in the etiology of OM, but the exact mechanism remains elusive.
Possibilities include inflammatory swelling of the middle earmastoidET mucosa;
allergic nasal obstruction; or the middle-ear mucosa reacting as a shock organ.
However, because large numbers of highly allergic children do not have significant otitis,
and many children with significant otitis do not have documented allergy, the relationship
is clearly not a straightforward one.
Children with congenital or acquired immunocompromise, although relatively small in
number, require special consideration, because they often are more susceptible to
infections, including OM, and to unusual organisms. Congenital immune abnormalities
include B-cell deficiencies, such as hypogammaglobulinemia and IgA deficiency; T-cell
deficiencies, such as DiGeorge syndrome; combined T- and B-cell deficiencies, including
ataxia telangiectasia; phagocyte defects, including Chdiak-Hagashi syndrome; and
complement deficiencies. Acquired abnormalities include those secondary to neoplasms
and inflammatory processes such as acute or chronic infec-tions. Drugs causing immune
deficiencies include steroids, chemotherapeutic agents, and antirejection agents used in
transplant patients. Although severe forms of immune deficiency are uncommon in
children, many of the otherwise normal otitis-prone children may have immature immune
systems as documented by poor response to polysaccharide antigen vaccines, including
HIB, tetanus, and the pneumococcal vaccine.
Abnormalities, either physiologic or anatomic, of the palate and associated musculature,
especially the tensor veli palatini, may cause or worsen ET dysfunction. For example,
many cra-niofacial abnormalities, including cleft palate, Crouzon syndrome, Apert
syndrome, and Down syndrome, are associated with abnormal skull base or palate shapes
with resultant ET dysfunction.
MICROBIOLOGY
The most commonly identified aerobic pathogens associated with AOM are
Streptococcus pneumoniae (30% to 50%), non-typable Haemophilus influenzae (20% to
30%), Moraxella catarrhalis (10% to 20%), and group A streptococci (1% to 5%) (2).
Other bacteria, such as Staphylococcus aureus and gram-negative enteric organisms,
including Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa, are
consistently isolated in a small proportion of patients. In neonates and young infants, S.
pneumoniae and H. influenzae are still the most commonly isolated pathogens; however,
S. aureus, group B streptococci, gram-negative enteric pathogens, and other organisms
are found up to 20% of the time. In immunocompromised children or those requiring
prolonged hospitalization, unusual organisms (e.g., Mycobacterium tuberculosis,
Mycoplasma pneumoniae, and Chlamydia trachomatis) have been isolated. M.
pneumoniae is an important upper respiratory pathogen in children and adults. Although
it has been infrequently isolated from middle-ear fluid in immunocompetent children, it is
not considered a major pathogen for OM. Chlamydia trachomatis is associated with
pneumonitis in infants, and has occasionally been isolated from the middle ear of infants
under 6 months of age.
Over the past decade, an increasing number of -lactamaseproducing bacteria causing
middle-ear disease have been isolated, with up to 30% of the H. influenzae and 100% of
the M. catarrhalis being -lactamase positive. Many of the Staphylococcus and anaerobic
organisms are -lactamase positive as well (3). Although S. pneumoniae does not make
-lactamase, other resistance factors, including chromosomal alterations, lead to a
decrease in penicillin binding proteins and an increase in resistance to sulfa,
chloramphenicol, tetracycline, and trimethoprim (19). The exact percentage of bacterial
resistance for any particular organism varies with the geographic area and the popu-lation
studied. Possible clinical factors in the development of bacterial resistance to
antimicrobials include multiple and prolonged courses (including prophylaxis), not taking
the entire prescribed course, and inappropriate administration. This last is now being
targeted in the treatment of OM.
In the past, chronic MEE was often thought to be sterile. However, several studies have
isolated S. pneumoniae, H. influenzae, M. catarrhalis, and group A streptococci in 30%
to 50% of children with chronic MEE (3). In 1995, Post et al. reported on the usefulness
of the polymerase chain reaction (PCR) in the detection of bacterial DNA in pediatric
MEE samples that were sterile by standard culture techniques (20). In this study, 77.3%
of patients tested PCR positive for one or more of the standard organisms (M. catarrhalis,
S. pneumoniae, or H. influenzae), whereas only 28.9% were both PCR and culture
positive for one or more of these organisms. No samples were culture positive and PCR
negative. Although these results are not proof of an active bacterial infectious process,
they suggest that bacteria may be present in a higher percentage of OME specimens than
previously thought. The role of anaerobic bacteria in chronic MEE remains unclear; they
have been isolated in 0% to 10% of chronic MEE samples (21). The most frequently
isolated bacteria in CSOM include P. aeruginosa, S. aureus, Corynebacterium, and
Klebsiella pneumoniae (3). Anaerobic bacteria play a minor role in the pathogenesis of
AOM. In CSOM, however, anaerobic organisms such as Peptostreptococcus, Fu-
sobacterium species, Propionibacterium acnes, and Bacteroides species most commonly
have been isolated.
The role of viruses as primary or copathogenic organisms in OM has gained increasing
attention. Viruses such as respiratory syncytial virus, rhinovirus, influenza virus,
adenovirus, enterovirus, and parainfluenza viruses have been isolated from middle-ear
fluids. Cytomegalovirus and herpes simplex viruses also have been isolated, although in a
smaller number of cases. Respiratory viruses may potentiate the possibility of
nasopharyngeal colonization with bacteria, further increasing the incidence of OM. Otitis
media is also known to accompany viral exanthems, including measles and the Epstein-
Barr virus.
EVALUATION
History
The diagnosis of OM is based on history and physical examination (Table 89.1). The
most common symptoms of AOM are otalgia, irritability, fever, lethargy, and otorrhea.
Fever is present in up to two thirds of children with AOM, but fevers over 40C are
uncommon and may represent bacteremia or other complications (Table 89.2). Other
symptoms associated with AOM include anorexia, nausea, vomiting, and headache.
Children who can verbalize may complain of hearing loss, dizziness, and tinnitus. For
infants and younger children, parents and caretakers may notice hearing loss or loss of
balance. Because the ET is less functional when the child is lying down, symptoms often
appear worse at night or during naps, with frequent awakenings. In children with OME,
hearing loss may be the only symptom. Children with draining ears, especially if chronic,
may have little or no pain, may sleep well, but may still complain of hearing loss and
occasional low-grade fevers. Children with TM perforations are usually asymptomatic
except for hearing loss, unless they get water in their ears, which may cause them
significant discomfort. Finally, children with atelectasis of the TM also are usually
asymptomatic, although many of these children experience hearing loss as well.

TABLE 89.1. DIAGNOSIS OTITIS MEDIA



TABLE 89.2. SIGNS AND SYMPTOMS OF OTITIS
MEDIA



Physical Examination
Although pneumatic otoscopy is the most important part of the physical examination for
OM, complete evaluation of the head and neck is essential. The pinna, external auditory
canal, TM, and middle-ear landmarks should be evaluated. If the ear is rotated forward
and there is edema or erythema of the posterior auricular sulcus, acute mastoiditis may be
present. Pneumatic otoscopy requires the child to be immobile but not uncomfortable. If
the child is extremely uncooperative or cannot be immobilized safely, sedation or general
anesthesia may be needed if the examination is felt to be very important for diagnosis and
treatment.
The normal TM is gray and translucent with normal mobility on pneumatic otoscopy.
Middle-ear landmarks that may be seen through a normal TM include the short process of
the malleus, the incudostapedial joint, and occasionally the chorda tympani. The position
of the TM can be neutral, bulging, retracted, or full. The color of an abnormal TM is
frequently opaque and may appear yellow or blue (indicating MEE), dark red (trauma,
hemorrhage), or red (AOM or hyperemia due to crying or coughing). The mobility of the
TM should be assessed on both positive and negative pressure. Decreased mobility of the
TM on both positive and negative pressure often indicates MEE, whereas movement only
with negative pressure suggests ET dysfunction. In the case of a patent tympanostomy
tube or TM perforation, there is no mobility of the TM. Middle-ear effusion can be
described as serous (thin, watery), mucoid (thick, viscous), purulent (puslike), or clear
(inflammatory, cerebrospinal fluid leak). Air-fluid levels or bubbles may be seen,
indicating intermittent aeration of the middle ear.
The location and size of a TM perforation should be noted; it can be of any size and there
may occasionally be more than one. An acutely perforated TM is erythematous and
thickened, with otorrhea discharging through the perforation. Perforations in the
posterosuperior quadrant can be difficult to visualize, and are often associated with
cholesteatoma. Evaluation of the TM may reveal other pathology, including
tympanosclerosis, retraction pockets, or areas of atelectasis. Tympanosclerosis appears as
white and thickened areas of the TM that must be distinguished from cholesteatoma.
Retraction pockets can be located anywhere in the TM and may represent areas of
atelectasis, healed tympanostomy tube or perforation sites, or the effect of persistent
negative middle-ear pressure.
Hearing Evaluation
Evaluation of hearing is an essential part of the workup in every patient with a history of
middle-ear disease. The method of audiologic workup can be divided into two groups: (a)
audiometric evaluation, to test the peripheral hearing; and (b) immitance audiometry to
evaluate the stiffness of the TM and middle-ear system. Conductive hearing loss is the
most common finding if there is a history of OM. The type of audiometric evaluation
varies based on the age of patient, level of cooperation, and maturity. Otacoustic
emissions are one of the techniques of choice for hearing screening in the newborn
nursery. Middle-ear effusion is one of the main causes of otacoustic emission failure;
therefore, it should not be used for evaluation of middle-ear disease. Auditory brainstem
response is the method of choice to distinguish conductive from sensorineural hearing
loss in infants under the age of 6 months. Auditory brainstem response is also
recommended in children who are unable to participate in other audiometric evaluations
due to lack of cooperation or maturity regardless of the age, or if ear-specific information
is needed. Behavioral observation audiometry (BOA) is recommended for infants 6
months to 1 year of age, and visual reinforcement audiometry (VRA) is used for toddlers
1 to 2 years of age. The accuracy of BOA and VRA relies on the level of experience of
the audiologist. BOA and VRA do not accurately differentiate between conductive
hearing loss and sensorineural hearing loss. Play audiometry is recommended in a
cooperative child over the age of 2 years, and is not only ear specific but also
distinguishes the type of hearing loss (conductive or sensorineural). Conventional
audiometry can be used in a cooperative child over 5 years of age.
Tympanometry is a measure of sound reflected by the TM and middle-ear structures. This
provides a graphic representation of compliance changes as the ear canal pressure is
varied. Different tympanometric patterns are associated with middle-ear and TM
pathology (Fig. 89.2). Measurement of ear canal volume can be undertaken to further
assess the status of the middle ear and specifically the TM. Children with a perforated
TM or patent tympanostomy tube will have a larger ear canal volume. Different
immitance audiometry techniques are available to further evaluate the middle ear if
needed.
Acoustic reflectometry is used to measure the total level of the reflected and transmitted
sound. A hand-held instrument is placed in the external auditory canal to provide an 80-
dB sound source that varies from 2,000 to 4,500 Hz in a 100-ms period. The sensitivity
and specificity of this method is operator dependent and varies from fair to excellent (3).
Although, acoustic reflectometry is not widely used for the diagnosis of middle-ear
disease, it can be a useful adjunct to otoscopy and impedance audiometry.
TREATMENT AND PREVENTION
The rationale for treating OM includes avoiding complications and treatment of
symptomatic disease. Secondary reasons include buying time until the child's ET function
and immune system have matured, and, in many cases, waiting for the end of the URI
season. Management is usually medical, with surgical intervention reserved for failures
of medical therapy (Table 89.3). Acute OM has a spontaneous resolution rate of about
60% to 80% (22). Reasons for spontaneous resolution may include drainage of MEE
down the ET or through a perforated TM, efficacy of local or systemic immunity, or
AOM, which has resulted from a virus or some noninfectious process. Sometimes the
diagnosis is in error, especially in a crying child with red eardrums. Based on these
findings, some investigators have felt that no initial antimicrobial therapy is indicated for
AOM, although medication to treat pain and fever can be given. If after a few days the
child is not significantly better, then antimicrobial therapy can be initiated. However,
several studies suggest that the resolution rate is higher if antimicrobials are given from
the beginning, and the complication rate may be lower as well. Some investigators that
have evaluated middle-ear fluid several days after the start of an acute infection have
found that S. pneumoniae is often the cause of persistent otitis. Because S. pneumoniae is
also associated with a large number of the complications secondary to OM, nontreatment
in the acute stage is at least worrisome. Based on all these factors, routine nontreatment
of symptomatic AOM is not advocated (2).

TABLE 89.3. TREATMENT OTITIS MEDIA



The routine treatment of asymptomatic middle-ear fluid is at least as controversial. The
child with asymptomatic middle-ear fluid typically often has (or has recently had) a viral
URI and the fluid is noted incidentally on physical examination; the TM is often dull but
not red or bulging, but TM mobility is limited and fluid or bubbles are noted. Although
the parents may have noted decreased hearing, the child has no other symptoms. In this
child, watchful waiting may be entirely appropriate. The key here is whether the child is
truly asymptomatic (no fever, pain, sleeping well at night, not off-balance) and has
reliable caretakers to make sure that the child returns for follow-up or to report if the
child develops symptoms consistent with AOM. However, this type of middle-ear fluid is
not necessarily sterile, with bacterial organisms documented 30% to 70% of the time by
conventional culture techniques and 77% by the polymerase chain reaction (3,20).
Therefore, symptoms of AOM should be treated (even in the presence of a previously
asymptomatic OM), and if the middle-ear fluid has been there for 3 months or more,
hearing evaluation and possible surgical intervention should be considered.
Medical Management: Antimicrobial Agents
The use of antimicrobial agents is the most common method of management of OM.
Because middle-ear culture material is usually not available, empiric therapy is aimed at
the most common bacteria isolated from the middle ear. Other factors that should be
considered in choice of antimicrobial agent are patient age, duration of disease, use of
other antimicrobials recently or in the past, and history of drug allergy. Amoxicillin still
remains the antimicrobial of choice for the treatment of a first episode of OM. Children
receiving appropriate antimicrobial treatment should show improvement within 48 to 72
hours). Additional therapy with analgesics may provide symptomatic relief. Change of
antimicrobial (-lactamaseproducing organisms) or tympanocentesis/myringotomy for
culture may be needed if there is no improvement or worsening of the condition. The
current standard of care is appropriate antimicrobial therapy for 10 days (or 5 days for
azithromycin), and follow-up in 2-4 weeks. Studies have shown that despite treatment,
there is persistent MEE after AOM in 40% of patients at 4 weeks, in 20% at 8 weeks, and
in 10% at 12 weeks (3,5) (Fig. 89.2). Further treatment is based on the frequency,
severity, and persistence of MEE.
Children with only occasional episodes of AOM that respond to antimicrobial therapy
and with resolution of MEE seldom require additional treatment. In children with
frequent OM (more than three or four in 6 months, or four to six in 1 year), other
treatment options should be considered. These children may be divided into two groups:
(a) those who clear the effusion between episodes; and (b) those with persistent effusion.
The options for those children who clear the MEE between episodes of OM include (a)
antibiotic treatment for each separate episode of AOM; (b) prolonged prophylactic
antibiotic treatment; and (c) myringotomy and ventilation tube insertion. Amoxicillin and
sulfisoxazole are the most widely used prophylactic agents. Prophylactic antimicrobials
can be considered in children who have had three to four or more episodes of recurrent
OM in 6 months, or four to six episodes in 1 year. Antimicrobial agents such as
amoxicillin, sulfisoxazole, and penicillin have been used in various studies to prevent
recurrent AOM (3). In general, younger children benefit more than older children do, and
the effect on the duration of MEE is not significant. There is increasing concern about the
use of long-term antimicrobial prophylaxis due to the increased rate of resistant
organisms (19,23). Additionally, when there are frequent breakthrough infections or
persistence of MEE, tympanostomy tubes should be considered.
Treatment should be considered for chronic OME that has persisted for 3 months or
longer, especially if the disease is bilateral, very symptomatic, and associated with
significant conductive hearing loss (especially if sensorineural hearing loss is also
present), and if there are significant TM changes, such as deep retraction pockets, or
middle-ear changes, such as adhesive otitis or ossicular involvement. If the disease has
been quite symptomatic, then antimicrobials, and occasionally steroids, already may have
been tried. If not, a trial of one or two antimicrobials that would be used for AOM can be
considered. However, the resolution rate, based on multiple studies using different
antimicrobials, is not as high as for AOM.
Multiple studies have used systemic and intranasal cortico-steroids for the prevention and
treatment of chronic MEE (22). The results of these studies vary and are difficult to
compare due to lack of uniformity in the steroid type, dosage, duration, and route of
administration, presence or absence of allergy, and with or without the use of
antimicrobial agents. Currently, it is difficult to recommend steroid use due to uncertain
efficacy and potential side effects.
Many other nonsurgical strategies have been suggested for treatment of chronic OME,
including decongestants/antihistamines, mucolytics, allergy therapy, ET inflation, and,
most recently, the use of xylitol chewing gum (3,24). Valsalva's maneuver or
politzerization may help to resolve effusion secondary to barotrauma or from infrequent
acute serous OM; however, there is very little evidence to support their use in patients
with long-standing MEE. However, studies of autoinflation using devices that provide
feedback to the patient have failed to show long-term improvement in MEE (25,26).
Finally, a 1996 study evaluated the use of xylitol chewing gum to prevent AOM in 5-
year-old children in day care. The investigators found a slight decrease in the otitis rate in
the children chewing xylitol (12.1%) versus sucrose (20.8%) gum (27). Although this is
an intriguing idea, the safety of xylitol in children of any age, the older age of the
children, and the slight difference in the otitis rate certainly warrants further study before
this treatment can be recommended.
Decongestants, both systemic and intranasal, continue to be frequently used in children
with OM, despite several clinical trials demonstrating lack of efficacy in curing or
preventing middle-ear disease. Similarly, decongestant/antihistamine combinations are
frequently prescribed for children with otitis; again there is no evidence that they change
the clinical course or prompt resolution of middle-ear fluid. There is some evidence that
ET dysfunction without middle-ear fluid may be helped by these agents, and there may
be improvement in nasal symptoms in children with allergic rhinitis. Additionally, these
drugs may have side effects and are not recommended for the treatment of OM (Table
89.4).

TABLE 89.4. POSSIBLE MANAGEMENT
STRATEGIES FOR OTITIS MEDIA WITH
EFFUSION



Prevention
Several measures have been suggested to prevent OM, including antimicrobial
prophylaxis, allergy control, tonsillectomy and/or adenoidectomy, vaccination, the
administration of immunoglobulins, and changing possible environmental contributors.
Allergy management may help if a specific allergen can be identified. Intravenous
gamma globulin may occasionally be recommended for proven or suspected
immunoglobulin deficiency. However, as in the case of allergies, specific medical or
surgical management of the otitis may be needed while waiting for the allergies to
become more controlled and for the immune system to mature. Changes in environmental
factors that may help decrease OM include removing possible allergens, prolonging
breast-feeding, removing the child from day care (or moving the child from a large day-
care situation to a small home-care situation), and preventing exposure to second-hand
cigarette smoke (3). Even though a direct cause-and-effect relationship between OM and
second-hand smoke has been difficult to consistently document, there are enough other
health hazards associated with cigarette smoking to make avoiding smoking around
children advisable.
Vaccines directed against the bacteria and viruses that are associated with OM provide an
intriguing method for possible prevention. Most of the vaccine research has been aimed
at S. pneumoniae and nontypable H. influenzae, especially important now that these
bacteria have developed significant antimicrobial resistance patterns. The older 23-valent
S. pneumoniae vaccine has not proven very immunogenic in children under the age of 6
years. However, the new heptavalent S. pneumoniae conjugate vaccine appears to be very
effective against invasive pneumococcal disease. Additionally, the vaccine appears to
have a significant impact on episodes and visits for otitis and tympanostomy tube
placement. This vaccine has the potential to reduce otitis, as well as other types of
pneumococcal disease, due to vaccine serotypes (28).
Vaccination against the viruses that are associated with OM also has been an intriguing
area of investigation. Clements et al. reported that children 6 to 30 months of age who
had received influenza vaccine had 32% fewer episodes of AOM than those who did not.
Although more studies are needed, these results provide encouragement for further study
(29).
Surgical Therapy: Myringotomy and Tube Insertion
The use of ventilation tubes has become the treatment of choice for (a) recurrent AOM
unresponsive to medical therapy; (b) chronic OM with bilateral persistent effusion greater
than 3 months and conductive hearing loss; (c) negative middle-ear pressure with
impending cholesteatoma; and (d) intervention in the presence of complications of OM.
Insertion of ventilation tubes not only normalizes the middle-ear pressure, it decreases the
frequency and severity of AOM, and generally resolves the conductive hearing loss
associated with persistent effusion (3,30). For children with very severe recurrent AOM,
both ventilation tube insertion and prophylactic antibiotics may be necessary. Children
requiring both tubes and antimicrobials to manage their otitis effectively often have mild
immune dysfunction that improves with time. Myringotomy and tube insertion may be
done under local (many adults) or general (most children) anesthesia depending on the
age and level of cooperation. The average time that tympanostomy tubes (TT) remain in
place and functional is 8 to 12 months after insertion.
Complications of ear tubes include otorrhea, persistent TM perforation when the tube has
extruded, scarring or tympanosclerosis involving the TM, plugging of the tube, formation
of granulation tissue around the tube, atrophic or thinned areas of the TM (where the tube
was), early extrusion or extrusion into the middle ear, and cholesteatoma. Otorrhea is
relatively common, occurring 12% to 30% of the time right after tube insertion,
especially if the MEE was purulent or mucoid, and in up to 50% of children at some point
during the time the tubes are in place. Otorrhea often occurs secondary to a URI.
Tympanic membrane perforations that do not close spontaneously occur in up to 3% of
ears with TT, although this number is higher with some tubes that were specifically
designed to stay in longer than regular tubes. Factors that may be related to a higher
persistent perforation rate include tube retention beyond 36 months and multiple sets of
tubes (3).
Adenoidectomy and Tonsillectomy
Historically, adenoidectomy has been recommended as an adjunctive treatment in the
management of chronic OM. However, the results of studies evaluating the efficacy of
adenoidectomy in preventing or decreasing middle-ear disease vary widely. There are
some fundamental differences with these studies with regard to (a) definition of OM, (b)
presence or absence of environmental allergy, (c) adenoid size, (d) status of ET, and (e)
concurrent surgeries (i.e., tonsillectomy). Two studies have shown that time to recurrence
of effusion, duration of effusion, and the need for further myringotomy were improved in
the adenoidectomy group (29,30). Paradise and colleagues also evaluated the usefulness
of adenoidectomy in the management of recurrent AOM, and showed that the number of
episodes of AOM was 35% in the adenoidectomy group versus 28% in the control group.
Gates and colleagues evaluated various combinations of myringotomy, adenoidectomy,
and tympanostomy tube placement for OME. They found that time with recurrent MEE
was decreased by 29% (tube only), 38% (adenoidectomy and myringotomy), and 47%
(adenoidectomy and tubes) (25,26).
Although there is anecdotal evidence that tonsillectomy is helpful, there is no study
demonstrating significant efficacy of tonsillectomy in prevention of OM over
adenoidectomy alone in the management of OM.
COMPLICATIONS
Since the introduction of antimicrobials, the incidence of both suppurative intratemporal
and intracranial complications has plummeted. However, complications still do occur,
and vigilance is needed to prevent the potential morbidity and mortality that can still be
associated with them (2). Complications can be divided into intratemporal and
intracranial groups (Table 89.5). By far the most common of these is conductive hearing
loss (CHL), usually due to the presence of middle-ear fluid. Within the past decade there
has been significant interest in the long-term effect of persistent MEE on speech,
language, and cognitive development of the child. Although many studies have been
done, the results remain controversial. In a review article on OM during early childhood
and its effect on development, Paradise noted possible reasons for discrepancies in these
types of studies, including (a) proper documentation of history of OM; (b) timing of
audiologic workup; (c) otologic status at the time of cognitive evaluation; and (d) varying
study populations (25). Teele and colleagues studied 207 children from birth to age 7 and
found that time spent with MEE was significantly associated with lower scores on tests of
cognitive ability, speech and language, and school performance (27). Studies also have
shown that the incidence of language delay in children prone to OM is more than
threefold that of children in the normal group (27). More recently, studies have started to
examine the long-term effects on hearing and central auditory processing brought about
by persistent effusion and conductive hearing loss. Despite the variance in study design
and results, there is enough concerning data that both the American Academy of
Pediatrics, through their Committee on Early Childhood, Adoption, and Dependent Care,
and the Agency for Health Care Policy and Research, through their clinical guidelines,
feel that there is growing evidence of correlation between middle-ear fluid with hearing
impairment and delays in language, speech, and cognitive development. If the effusion
has persisted for 3 months or longer, especially if it is bilateral, hearing and
communication skills should be evaluated (31).

TABLE 89.5. COMPLICATIONS OTITIS
MEDIA



Fortunately, given the high incidence of OM, there are infrequent emergent situations.
Table 89.6 briefly outlines some of the warning signs for potentially complicated OM. If
the patient continues to be febrile, to have severe pain, or to exhibit any of the
complications listed in Table 89.5, immediate intervention should be considered. A high
index of suspicion should be used in evaluating neonates and immunocompromised hosts
because they may have unusual organisms that do not respond to the usual antimicrobial
agents. Initial studies include physical examination and tympanocentesis to obtain an
organism for culture and susceptibility testing; wide-field myringotomy with insertion of
a tympanostomy tube also should be considered at this time. Computed tomographic
scanning can help to identify intracranial and intratemporal complications. If the patient
does not respond promptly to intravenous antimicrobials and
tympanocentesis/myringotomy, tympanomastoidectomy should be considered. If
intracranial complications are suspected or confirmed, neurosurgical consultation should
be obtained.

TABLE 89.6. EMERGENCIES OTITIS MEDIA



SUMMARY
Otitis media is one of the most common diseases of childhood, and represents a costly
medical problem. Factors such as the emergence of resistant bacterial organisms, frequent
introduction of new antimicrobial agents, and lack of consensus on the role of allergy,
gastroesophageal reflux, and viral infection continues to challenge us with respect to
diagnosis and treatment. Further studies are also needed to properly evaluate the effect of
middle-ear disease on speech, language, and cognitive development.

HIGHLIGHTS
Otitis media represents an inflammatory condition of the
middle-ear space, without reference to pathogenesis.
Otitis media is the second most common disease of childhood
after URIs.
Two thirds of children have at least one episode of OM by 3
years of age.
After an episode of AOM, 10% of children have MEE lasting 3
months or more.
Epidemiologic factors associated with an increased incidence of
OM include group day care, parent or sibling with OM,
possibly male sex, and smoking.
The most common bacterial organisms causing AOM are S.
pneumoniae, H. influenzae, M. catarrhalis, and group A
streptococci.
Fifty percent of children with OME have bacterial organisms
cultured from their MEE, including S. pneumoniae, H.
influenzae, and M. catarrhalis; close to 80% have evidence of
bacterial persistence by PCR.
Eustachian tube dysfunction appears to be the most important
factor in the pathogenesis of middle-ear disease.
Prolonged MEE associated with hearing loss may interfere with
speech and language development.
Modification in factors such as allergens, day-care settings,
exposure to second-hand cigarette smoke, and duration and
position (upright versus supine) of breast-feeding may play a
role in the frequency of OM.
Life-threatening complications of OM are uncommon but do
occur and can have severe neurologic sequelae, including death.
The management of OM is initially medical, with surgical
therapy usually reserved for medical failures or complications.
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1988:107(suppl 457):133138.
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19. Kenna MA. The problem of resistant pneumococcus. Curr Opin Otolaryngol Head Neck Surg
1995;3:374378.
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effusion. JAMA 1995;273:15981604.
21. Kaleida PH, Kenna MA, Stephenson JA, et al. Do anaerobic bacteria play a major etiologic role in
children with chronic otitis media with effusion? In: Lim DJ, Bluestone CD, Klein JO, et al., eds.
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1998;17:10901098.
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double blind randomised trial. BMJ 1996;313:11801184.
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in the treatment of chronic otitis media with effusion. N Engl J Med 1987;317:14441451.
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media in infancy and intellectual ability, school achievement, speech, and language at age 7 years.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

90 GENETIC HEARING LOSS
Head & Neck SurgeryOtolaryngology
90




GENETIC HEARING LOSS
PATRICK E. BROOKHOUSER

P.E. Brookhouser: Boys Town National Research Hospital, Omaha, Nebraska.


Basic Genetic Principles
Genetic Linkage Analysis
Structural Malformations of the Inner Ear
Michel Aplasia
Mondini Aplasia
Scheibe Aplasia
Alexander Aplasia
Enlarged Vestibular Aqueduct
Semicircular Canals
Autosomal Dominant Disorders
Waardenburg Syndrome
Stickler Syndrome
Branchiootorenal Syndrome
Treacher Collins Syndrome
Neurofibromatosis
Otosclerosis
Nonsyndromic Autosomal Dominant Hearing Loss
Dominant Progressive Hearing Loss
Recessive Disorders
Usher Syndrome
Pendred Syndrome
Jervell and Lange-Nielsen Syndrome
Nonsyndromic Recessive Sensorineural Hearing Loss
Sex-Linked Disorders
Norrie Syndrome
Otopalatodigital Syndrome
Wildervanck Syndrome
Alport Syndrome
Deafness Dystonia Syndrome
Nonsyndromic X-Linked Hearing Loss
Multifactorial Genetic Disorders
Chromosomal Syndromes
Down Syndrome
Turner Syndrome
Mitochondrial Inheritance
Evaluation and Genetic Counseling
Chapter References
Bibliography
Population studies, based principally on pupil records from schools for the deaf, have
historically attributed about 50% of childhood sensorineural hearing loss (SNHL) to
genetic factors (Fig. 90.1). About 20% to 25% of cases have been assigned to identifiable
environmental causes, prenatal, perinatal, or postnatal, and 25% to 30% are classified as
sporadic cases of unknown causation, undoubtedly comprising to some degree
nonsyndromic genetic losses. The past several decades have witnessed major changes in
the mix of causes of SNHL reflected in each successive cohort of children with SNHL.
Once-prevalent nongenetic causes of SNHL, including rubella, measles, mumps, and
Haemophilus influenzae B meningitis, are nearly disappearing in developed countries
because of mass immunization of susceptible infants and children. Diagnostic techniques
entailing polymerase chain reaction technology facilitate definitive confirmation of
congenital infection from traces of infectious agents obtained during amniocentesis. The
cumulative result of these advances should be a relative increase in the prevalence of
genetic SNHL among future cohorts of affected children. The mandate is for increased
clinician familiarity with the full spectrum of these disorders.

FIGURE 90.1. Causes of deafness, total population.



Genetic hearing loss may be congenital or delayed, that is, postnatal, in onset;
conductive, sensorineural, or mixed in type; mild to profound in degree; progressive or
nonprogressive; unilateral or bilateral and symmetric or asymmetric in severity and
configuration; and syndromic (involving identifiable characteristics in other systems) or
nonsyndromic (involving only hearing loss). More than 400 different genetic syndromes,
many quite rare, that include hearing loss have been identified. They are commonly
classified according to the other systems involvedcraniofacial and cervical, skeletal,
integumentary, ocular, neurologic, renal, metabolic, and other. Nonsyndromic hearing
disorders (hearing loss only) typically have been classified rather simplistically according
to the audiologic characteristics, age at onset, presence or absence of progression, and
mode of inheritance. Most authors attribute 75% to 80% of cases of genetic deafness to
autosomal recessive genes and 18% to 20% to autosomal dominant genes. The others are
classified as X-linked or chromosomal disorders. Greater accuracy in these estimates has
been precluded by the challenge of positively identifying singleton cases of
nonsyndromic SNHL, particularly the recessive type.
BASIC GENETIC PRINCIPLES
Human genes, molecular codes for inherited factors, are arranged linearly on 23 pairs of
chromosomes, including 22 pairs of autosomes and one pair of sex chromosomes (male
XY; female XX) (Fig. 90.2). Thus there are 46 chromosomes in all. Men and boys have
an X and a Y as the pair of sex chromosomes, and women and girls have two X
chromosomes. Each chromosome pair carries a distinctive set of gene loci, and a given
gene can have several alternative codes or alleles. The genotype for a specific trait can
consist of two identical alleles (homozygous) or two disparate alleles (heterozygous). The
phenotype, or physical manifestation of a trait, is determined by which alleles are present
and how they interact. An allele is dominant if it is phenotypically expressed whether
present in the homozygous or heterozygous state, whereas an autosomal recessive allele
must be present homozygously to be expressed. An X-linked recessive gene also is
expressed in the hemizygous state (only one allele) in men and boys, because the Y
chromosome does not carry a complementary allele.

FIGURE 90.2. Typical chromosome.



Dominant traits typically are transmitted from one generation to the next. There is a 50%
chance that an affected heterozygote will transmit the gene to each child. In some
instances, a dominant gene has lack of penetrance, so not all persons heterozygous for the
gene manifest the disorder. Dominant disorders also can have variable expressivity,
whereby different family members have different manifestations of the gene.
Environmental influences or interaction with other genes can modify phenotypic
expression in these cases.
An autosomal recessive trait may be seen in only one set of siblings in a family, and the
children of heterozygotic (carrier) parents have a 25% recurrence risk. An X-linked
recessive trait can be carried by a heterozygous woman without phenotypic expression,
but her sons have a 50% chance of inheriting the gene, which would be expressed in the
absence of a second X chromosome. The daughters of a female carrier have a 50% risk of
being carriers of such a trait. Because they inherit his Y chromosome, sons of an affected
man with a sex-linked trait are not affected, whereas all of the daughters of the affected
man carry the gene because they all inherit his X chromosome.
Heritable disorders, which are caused by abnormalities at the chromosomal level and
involve extra or absent chromosomal material, are characterized by varied congenital
anomalies and developmental delays except when they involve the sex chromosomes.
The nature and severity of the resultant phenotype depends on the quantity and
chromosomal origin of the material involved. Three copies of an entire chromosome are
present in persons with trisomy. Trisomy 21, or Down syndrome, is the least severe
autosomal trisomy. Trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome)
are less common and more severe. Other autosomal types of trisomy usually are lethal, as
is the condition known as monosomy, in which only one chromosome rather than a pair is
present. Embryos with sex chromosome abnormalities are quite viable, with the
exception of a conceptus with only a Y chromosome. In particular, persons with one extra
X or Y or with monosomy X have relatively mild clinical features, such as 47,XYY or
47,XXY (Klinefelter syndrome) and 45,X (Turner syndrome).
GENETIC LINKAGE ANALYSIS
Two genetic loci are said to be linked when they are sufficiently close together on the
same chromosome that their alleles are transmitted together more often than expected by
chance. The converse of linkage, random assortment, occurs when the genes are on
different chromosomes or are far enough apart on the same chromosome that crossover
occurs 50% of the time. If the chromosomal location of one gene locus is known, the
location of the linked locus is automatically determined. Conversely, the absence of
linkage between a disorder and a marker excludes the gene from the region of the
genome in the vicinity of the marker. Linkage analysis with family studies is performed
by means of comparing the segregation of a trait with the segregation of a battery of
known marker genes to see whether one of the markers is close to the gene for the trait.
Linkage analysis relies on the use of DNA markers based on inherited variations
(polymorphisms) in DNA sequence so that almost any part of the genome contains
identified sites. In addition to providing comprehensive human chromosome base
sequence data, the Human Genome Project has identified a series of DNA markers that
cover all of the chromosomes. Almost any gene can be placed near a known marker
sequence. Genetic heterogeneity for a trait is established when linkage between a trait and
a marker locus is proved in some families, but other families either exclude linkage with
that marker or have linkage with a different marker.
Genetic heterogeneity must be considered in studies of both syndromic and
nonsyndromic hearing loss. In hearing loss syndromes, the features must be carefully
examined to determine whether interfamilial differences can define subtypes attributable
to different genes. Nonsyndromic deafness poses an even greater challenge because no
clinical features clearly define subtypes, and genetic studies have indicated a high degree
of heterogeneity. For autosomal recessive nonsyndromic deafness, the number of genes
involved may exceed 100. The study of inbred or isolated study populations reduces
heterogeneity and has allowed identification of a number of recessive genes, whereas
studies of large kindreds can reduce heterogeneity for dominant conditions. After a gene
has been localized to a specific chromosomal region, physical mapping techniques are
used to isolate the DNA from the critical region, and sequences known from previous
data to be from expressed genes can be examined as possible candidates for the hearing
loss gene. Because considerable homology exists between portions of the human genome
and the genome of lower animals, such as mice, results of comparative genetics studies
can be reviewed for possible candidate genes for the human disorder being studied.
Libraries of genes expressed in cochlear tissue of mice and humans are a valuable source
of genes the mutation of which can cause hearing loss. The hereditary hearing loss home
page (http://dnalab-www.uia.ac.be/dnalab/hhh) is a helpful site on the World Wide Web
that provides current information on the genes responsible for hereditary hearing loss.
To verify that a mutation in a gene causes deafness, it must be ascertained that the
mutation does not occur in a control population. It also should be determined that the
mutation disrupts the function of the gene. This determination is made through
knowledge of the operation of the protein or by means of gene expression analysis in a
model system. The exact mutation that disrupts the function of a particular gene can vary
from family to family, however.
STRUCTURAL MALFORMATIONS OF THE INNER EAR
The cochlea reaches full growth (2 turns) by the end of the eighth week of gestation.
Hearing loss can be associated with agenesis or dysgenesis of inner ear components, so
that inner ear anomalies can be caused by arrests in normal development, aberrant
development, or both. Systems of clinical and histopathologic classification divide the
disorders according to the severity of the hearing loss and the site of developmental
failure. Temporal bone imaging techniques show that approximately 20% of children
with congenital SNHL have subtle or severe abnormalities of the inner ear.
Approximately 65% of such abnormalities are bilateral, and 35% are unilateral. The
range of abnormality depends on the period of embryologic development interrupted and
how it is interrupted. Jackler and DeLaCruz (1) conducted a systematic study in which
they correlated the type of deformity with the timing of developmental insult. On the
basis of the results of histopathologic studies of the temporal bone, inner ear
malformations have been classified into the following five groupsMichel aplasia,
Mondini aplasia, Scheibe aplasia, Alexander aplasia, and enlarged vestibular aqueduct.
Michel Aplasia
In Michel aplasia, the structures of the inner ear do not develop. The aplasia can include
complete agenesis of the petrous portion of the temporal bone while the external and
middle ear are completely unaffected. This malformation is thought to be caused by an
insult or developmental error before the end of the third gestational week, when the otic
placode is formed on the lateral surface of the neural tube. Temporal bone imaging is
critical in identifying the deformity, but certainty of diagnosis must await postmortem
histopathologic examination because labyrinthitis ossificans cannot be differentiated
radiographically. Anacusis is the presenting audiologic pattern. Neither conventional
amplification nor cochlear implantation is useful to these patients, but vibrotactile devices
can be used with some success. Thorough genetic studies have not been performed with
humans, but mouse models suggest that a number of different genes can cause this form
of aplasia. Autosomal dominant inheritance has been observed in mice, but recessive
inheritance also is likely.
Mondini Aplasia
In Mondini aplasia the cochlea is developmentally deformed whereby only the basal coil
can be clearly identified. His-topathologic examination shows that the upper coils assume
a cloacal form in the absence of an interscalar septum and that the endolymphatic
aqueduct is typically enlarged. Developmental arrest at approximately the sixth week of
gestation has been postulated as most likely in these cases because the anatomic status of
the labyrinth, including underdevelopment of the vestibular labyrinth, parallels this stage
of development most closely. Mondini aplasia is not necessarily bilateral, and both
dominant and recessive, syndromic and nonsyndromic forms have been described,
including occurrence with Pendred, Waardenburg, branchiootorenal, Treacher Collins,
and Wildervanck syndromes. An association between Mondini aplasia and nongenetic
etiologic factors, such as congenital cytomegalovirus infection, also has been reported.
The presence of neurosensory structures in most cases warrants an aggressive program of
early habilitative intervention that includes conventional amplification. Progression of the
hearing loss also has been reported. The progression may be related to recurrent
disruption of the intra-labyrinthine membrane or perilymphatic fistulae.
Scheibe Aplasia
In Scheibe aplasia the bony labyrinth is normally differentiated, as is the superior portion
of the membranous labyrinth, which includes the utricle and semicircular canals.
Examination of the saccule and cochlear duct, however, shows that the organ of Corti is
poorly differentiated, the tectorial membrane is malformed, and the scala media is
compromised by collapse of the Reissner membrane. Scheibe aplasia, which is the most
common form of inner ear aplasia, can be inherited as an autosomal recessive
nonsyndromic trait. Histopathologic study of temporal bones has shown Scheibe aplasia
among persons with the recessive Jervell and Lange-Nielsen, Refsum, and Usher
syndromes, and among those with dominant syndromes such as Waardenburg. This
malformation also occurs in the temporal bones of infants with congenital rubella
syndrome and includes documented SNHL. Selected conventional amplification has
proved beneficial in many of these cases.
Alexander Aplasia
Aplasia of the cochlear duct, which affects the organ of Corti and ganglion cells at the
level of the basal coil, characterizes Alexander aplasia. The most commonly observed
audiometric configuration is high-frequency hearing loss with adequate residual hearing
in the low frequencies to warrant use of amplification by these children.
Enlarged Vestibular Aqueduct
The association of an enlarged vestibular aqueduct with early-onset SNHL has been
shown radiographically. The deformity and hearing loss usually are bilateral, and
children may have vertigo or lack of coordination. Enlarged vestibular aqueduct can
accompany deformities of the cochlea and semicircular canal. Hearing loss often is
progressive, presumably because of hydrodynamic changes and possibly because of
disruption of the labyrinthine membrane. Attempts to prevent progression of hearing loss
with surgery proved unsuccessful and are no longer advocated. The existence of familial
suggests autosomal dominant inheritance, but the most common cause can be recessive.
Homozygous mutation of the PDS gene, which produces Pendred syndrome, also can
cause isolated enlarged vestibular aqueduct.
Semicircular Canals
The semicircular canals begin to form during the sixth gestational week. The superior
semicircular canals are the first to form. The lateral semicircular canals are the last to
develop and thus having the longest period of susceptibility to teratogenic insults. Jackler
and DeLaCruz (1) found deformities of the superior semicircular canals were invariably
accompanied by anomalies of the lateral semicircular canals, whereas abnormalities of
the lateral semicircular canals often occurred in isolation. Deformities of the lateral
semicircular canals are the most commonly identified inner ear malformation on
radiographic imaging studies.
AUTOSOMAL DOMINANT DISORDERS
Identification of an autosomal dominant syndrome is facilitated by a family history that
reflects a classic dominant inheritance pattern and a recognizable phenotype. In reality,
variation in expressivity of dominant genes frequently leads to the presence of different
phenotypic characteristics in various affected members of the same family. Decreased
penetrance also is common with dominant genes, so an obligate carrier of the gene may
not have any detectable phenotypic expression. When a new mutation has occurred, an
individual with no family history of the trait can actually have a disorder transmitted to
offspring in a dominant manner.
Waardenburg Syndrome
Waardenburg syndrome, first characterized in 1951, accounts for approximately 3% of
cases of hearing loss among childhood and is a notable example of a syndrome with
variable expressivity. In addition to unilateral or bilateral SNHL, phenotypic expressions
of Waardenburg syndrome include pigmentary anomalieswhite forelock,
heterochromia irides, premature graying, and vitiligoand craniofacial features such as
dystopia canthorum, broad nasal root, and synophrys. The white forelock is present in
only 20% to 30% of cases with a variable age of first appearance. The other features are
equally variable. Hair coloring can be used to disguise the forelock, further confounding
attempts at accurate diagnosis.
The two clinical types of Waardenburg syndrome are differentiated on the basis of the
presence (WS1) or absence (WS2) of dystopia canthorum. Hearing loss occurs among
approximately 20% of individuals with WS1 and more than 50% of those with WS2.
Lateral displacement of the medial canthi may not be immediately apparent, and indices
based on objective measures of the distances between landmarks such as the inner canthi,
the pupils, and outer canthi are helpful in making a determination. If only one or a few
characteristics are present in each family member, definitive diagnosis of Waardenburg
syndrome can be difficult. The importance of a complete history of the extended family
in questionable cases cannot be overstated.
Audiologic screening of family members can help identify previously unsuspected
unilateral hearing loss (Fig. 90.3). Almost all cases of WS1 are caused by mutation of the
PAX3 gene located on chromosome 2q37. Mutation of the mouse homolog of this gene
produces a condition called splotch, which includes pigmentary and ocular abnormality in
the heterozygote. Only the homozygote is deaf, however, and has much more severe
neural tube defects. Approximately 20% of cases of WS2 are attributable to a mutation of
the MITF gene (microphthalmia transcription factor) on chromosome 3p. Again, a mouse
homolog with mutation of the same gene is known, but these animals are not deaf in the
heterozygous state.

FIGURE 90.3. Asymmetric hearing loss in a patient with
Waardenburg syndrome.



Waardenburg syndrome type III (WS3), sometimes called Klein-Waardenburg syndrome,
includes the features of WS1 and skeletal malformations, particularly of the hands and
forearms. Waardenburg syndrome type III is caused by mutations of the PAX3 gene.
Waardenburg syndrome type IV (WS4) also is known as Waardenburg-Shah syndrome
and differs from the other three types in being autosomal recessive. Phenotypic features
are similar to those of WS2 with the addition of Hirschsprung megacolon. Waardenburg
syndrome type IV can be caused by mutations in one of three genes, the endothelin-B
receptor gene (EDNRB), endothelin 3 (EDN3), or SOX-10.
Stickler Syndrome
Stickler syndrome is an autosomal dominant disorder characterized by a small jaw. It is
often accompanied by a cleft palate (Robin sequence), myopia severe enough to be
associated with retinal detachment or cataracts, hypermobility and enlargement of joints
with early adult onset arthritis, and occasionally by spondyloepiphyseal dysplasia.
Substantial sensorineural or mixed hearing loss is expressed in approximately 15% of
cases and often is progressive. Lesser degrees of hearing occur in as many as 80% of
cases. The variation in expressivity that occurs with Stickler syndrome can be attributed
to both allelic and genetic heterogeneity and complicates diagnosis of the disorder. Some,
but not all, cases are associated with various mutations of the type II collagen gene
(COL2A1) on chromosome 12. Different mutations of the same gene produce the similar
but more severe syndromes of Kniest syndrome and spondyloepiphyseal dysplasia
congenita, which also include progressive SNHL.
Branchiootorenal Syndrome
Branchiootorenal, or Melnick-Fraser, syndrome involves bran-chial characteristics, such
as ear pits (possibly tags) or cervical fistulae, and renal involvement that ranges from
agenesis and renal failure to minor dysplasia, which usually is asymptomatic but can be
detected with ultrasonography or intravenous pyelography. The hearing loss can be
sensorineural, conductive, or mixed, and Mondini aplasia or a small cochlea also can be
present. Branchiootorenal syndrome affects as many as 2% of children in schools for the
deaf. This emphasizes the value of evaluating the renal status of any child with a hearing
loss and ear pit or branchial cleft anomaly. The gene on chromosome 8q is the human
homolog of the developmental Drosophila gene eyeless.
Treacher Collins Syndrome
Treacher Collins syndrome (mandibulofacial dysostosis) (Fig. 90.4) is a craniofacial
disorder with manifestations that include microtia, aural meatal atresia, and conductive
hearing loss approximately 30% of the time. Sensorineural hearing loss and vestibular
dysfunction also may be present. Malar hypoplasia, including underdeveloped zygomatic
arches with resultant downward slanting palpebral fissures, coloboma of the lower
eyelids, and a hypoplastic mandible are the usual facial findings. Symmetric facies and
bilateral eyelid coloboma differentiate Treacher Collins from Goldenhar syndrome and
other oculoauricular vertebral syndromes that include similar but unilateral microtia and
craniofacial abnormalities. Ossicular malformation often occurs among children with
conductive hearing losses, but otologic reconstructive procedures on these youngsters can
be fraught with technical challenges. Treacher Collins syndrome is transmitted in an
autosomal dominant manner with high penetrance. The oculoauriculovertebral spectrum
is sporadic and thought to be multifactorial. Treacher Collins syndrome can be caused by
a new mutation among as many as 60% of affected individuals. Genetic counseling must
be predicated on careful diagnostic study to differentiate it from the
oculoauriculovertebral spectrum. The gene that causes Treacher Collins syndrome
(TCOF1) has been identified on chromosome 5q, and the resulting protein has been
named treacle. It apparently functions in early craniofacial development. There is no
evidence of genetic heterogeneity, but there is considerable variation in expression
between and within families. This indicates that other genes can modify the expression of
the treacle protein.

FIGURE 90.4. Child with Treacher Collins syndrome.



Neurofibromatosis
Findings among persons with neurofibromatosis include caf au lait spots (light brown,
variable-sized pigmented spots) and multiple fibromas. This disorder is genetically
heterogeneous with two distinct forms. Classic neurofibromatosis (von Recklinghausen
disease, or NF1), with an incidence of approximately 1 case per 3,000 persons per year, is
associated with a very large number of caf au lait spots and cutaneous neurofibromas, as
well as plexiform neuromas, pseudoarthrosis, particularly of the tibia, Lisch nodules
(harmatomas) of the iris, and optic gliomas. Although cutaneous tumors are most
common, the central nervous system, peripheral nerves, and viscera also can be involved.
The phenotype can be limited to a few caf au lait spots or be expressed as multiple
disfiguring tumors. Central nervous system lesions can produce mental retardation,
blindness, or hearing loss, but these complications are not common. Hearing loss can be
caused by a neurofibroma encroaching on the middle or inner ear, but marked deafness is
rare. True acoustic neuroma, typically unilateral, occurs among only 5% of patients.
Children with this disorder need mandatory longitudinal audiologic follow-up
evaluations.
Central neurofibromatosis (NF2) is a genetically distinct disorder characterized by
bilateral acoustic neuromas (vestibular schwannomas). These lesions usually are slow-
growing and asymptomatic until young adulthood, when tinnitus and vestibular
dysfunction often are initial findings. Caf-au-lait spots and cutaneous neurofibromas
occur but affect fewer persons than do the lesions of von Recklinghausen disease. Central
neurofibromatosis, however, is associated with higher risk of tumors of the central
nervous system and spinal cord. Optic glioma and Lisch nodules have not been found
among persons with NF2. Both types of neurofibromatosis are inherited as autosomal
dominant conditions with high penetrance but variable expressivity. High mutation rates
characterize both disorders. Neurofibromatosis type 1 is caused by a nerve growth factor
gene on chromosome 17. Neurofibromatosis is caused by mutation of a tumor suppressor
gene on chromosome 22.
Otosclerosis
Studies of otosclerosis point to autosomal dominant inheritance with decreased
penetrance, meaning that the gene is not expressed in all of the persons who carry it.
Penetrance rates of 25% to 40% have been estimated, but genetic heterogeneity is likely
in this disorder. Some genes are more penetrant than others, and the preponderance of
affected women suggests a hormonal influence. Histopathologic examination shows
measles virus particles within the bony overgrowth. This finding raises the possibility of
an interaction with the viral genome. Contributions by the gene for the 1 chain of type 1
collagen (COL1A1) and by an unknown gene located on chromosome 15 have been
found.
NONSYNDROMIC AUTOSOMAL DOMINANT HEARING LOSS
Several recognized types of nonsyndromic, autosomal dominant hearing loss were
described in detail by Konigsmark and Gorlin (2). Congenital, severe nonprogressive
hearing loss represents more than one disorder. Several different genes have been
localized, but systematic study of temporal bones and audiologic data obtained from
affected persons is essential to clinical differentiation of these subtypes.
Dominant Progressive Hearing Loss
Dominant progressive hearing loss (DPHL) is a type of nonsyndromic, noncongenital
SNHL. It is variable in age at onset and rate of progression, which is inherited in an
autosomal dominant manner. Dominant progressive hearing loss is idiopathic and can be
differentiated from otosclerosis by the absence of ossicular and otic capsule involvement
and from presbycusis by the earlier age at onset, ranging from early childhood in some
families to early adulthood in others. Presymptomatic gene carriers may have elevated
thresholds for stapedial reflexes and positive signs of recruitment. Although many types
of DPHL progress to the level of severe to profound hearing loss, the initial frequencies
involved and the rate of progression can be quite different among families.
Konigsmark and Gorlin (2) defined four types of DPHLearly onset, high frequency,
mid frequency, and low frequency. Each of these subtypes also is heterogeneous; for
example, four types of high- frequency DPHL have been described according to the
slopes of audiograms within family groups. This clinical variation between families but
consistency within families suggested genetic heterogeneity, which has been confirmed
with linkage analysis. At least 38 genes that cause dominant nonsyndromic hearing loss
have been localized, and most show progression. These genes are given the designation
DFNA, followed by a number that indicates the order of discovery. Approximately one
fourth of these genes have been identified. These include genes for membrane pores
involved in signal transduction such as the KCNQ4 gene, which is a voltage-gated
potassium channel at the DFNA2 locus; connexins 26, 30, and 31, which are gap junction
proteins at the DFNA3/DFNB1 and DFNA2 locations; structural proteins such as myosin
VIIa, which causes DFNA11 in addition to DFNB2 and Usher 1b; COCH, which causes
DFNA9 and apparently is a structural binding protein; TECTA, a structural gene of the
tectorial membrane that causes DFNA12; COL11A2, a collagen gene responsible for
DFNA13; developmental regulators such as POU4F3, a transcription factor that causes
DFNA15; HDIA1, a gene with homology to the diaphanous gene in Drosophila that
which causes DFNA1; and the DFNA5 gene, the function of which is unknown. The
frequency of DPHL or of the subtypes in the general population is unknown.
RECESSIVE DISORDERS
Approximately 80% of genetic deafness in childhood is characterized by autosomal
recessive inheritance, and approximately one half of such cases represent recognizable
syndromes (Table 90.1). The asymptomatic status of heterozygote carriers of a recessive
gene, coupled with a recurrence risk of only 25%, means there is little likelihood that
more one child in the average-sized family will be affected. A clinician can be confronted
by a single affected child in a family with no known history of the disorder, making
differentiation between a recessively inherited disorder and a nongenetic one ex-tremely
difficult. Identification of recessive syndromes that include hearing loss necessitates a
diligent search by clinicians for other syndromic components. This diagnostic puzzle can
be clarified by a working knowledge of other organ system manifestations commonly
associated with recessively transmitted hearing loss.

TABLE 90.1. CLONED GENES FOR SYNDROMIC
HEARING IMPAIRMENT



Usher Syndrome
Usher syndrome, characterized by hearing loss and retinitis pigmentosa, has an estimated
frequency of 3.0 cases per 100,000 persons in Scandinavia and 4.4 cases per 100,000
persons in the United States. Although initially recognized by Von Graefe (1858), the
syndrome was named for Usher (1935), who emphasized the hereditary nature.
Prevalence estimates of Usher syndrome among populations of deaf persons have varied
from 0.6% to as high as 28% depending on the source of the study population. Usher
syndrome affects approximately one half of 16,000 deaf and blind persons in the United
States. Genetic linkage studies have shown Usher syndrome to be genetically
heterogeneous with three clinically distinct subtypes that can be differentiated on the
basis of severity or progression of the hearing loss and the extent of vestibular system
involvement. Clinically, patients with Usher syndrome type I (USH1) have congenital
bilateral profound hearing loss and absent vestibular function. Patients with Usher
syndrome type II (USH2) have moderate losses and normal vestibular function (Fig.
90.5). Usher syndrome type III (USH3) involves progressive hearing loss and variable
vestibular dysfunction and occurs primarily among the Norwegian population. Genetic
heterogeneity occurs within as well as between these subtypes. Linkage analysis studies
reveal at least six different genes for USH1 and at least three for USH2. Only USH3
appears to be caused by one gene. Only two of the genes have been identified. Usher
syndrome type I is caused by mutations in the myosin VII gene (MYO7A). Usher
syndrome type IIA is caused by mutation in a gene called USH2A, which produces a
protein called usherin. The function of this gene is unknown, but it shares homology with
laminin and fibronectin proteins.

FIGURE 90.5. Typical hearing losses among patients
with Usher syndrome types I and II. (From Moller C,
Kimberling WJ, Davenport SLH, et al. Typical hearing
losses in patients with Usher syndrome type I and Usher
syndrome type II. Laryngoscope 1989;99:73, with
permission.)



An ophthalmologic evaluation is integral to the diagnosis of Usher syndrome. Results of
electroretinographic studies have been reported to be subnormal among patients 2 to 3
years of age before functional or fundoscopic abnormalities can be detected. In early
studies, it was estimated that USH1 accounted for nearly 90% of cases of Usher
syndrome and that USH2 represented 10% or fewer. Because patients with USH2 with
moderate hearing losses are not typically educated in schools for the deaf, these early
studies underestimated the prevalence of this syndrome. Reports from both Scandinavia
and the United States reflect a nearly equal number of cases of USH1 and USH2 in large
series of patients. Early diagnosis of Usher syndrome can have important implications in
rehabilitation and educational planning for an affected child.
Pendred Syndrome
Pendred syndrome, described in 1896, is an autosomal recessive disorder in which SNHL
is associated with abnormal iodine metabolism; the typical result is a euthyroid goiter.
Hearing loss can be profound at birth, or it can be progressive. Radiologic studies show
that most of these patients have Mondini aplasia or enlarged vestibular aqueduct.
Diagnosis rests on a perchlorate discharge test result that shows abnormal organification
of nonorganic iodine, although this test is not specific for Pendred syndrome, and its
sensitivity is not known. Although the goiter usually becomes clinically evident at
approximately 8 years of age, it can be detected at birth in some cases. Exogenous
thyroid hormone is the best therapy. Surgical extirpation of the gland has proved
ineffective and is not recommended. The gene that causes Pendred syndrome has been
identified and named PDS. It produces a protein called pendrin, which is responsible for
iodine and chloride ion transport. So far, all known families with Pendred syndrome have
linked to this gene; there has been no evidence of genetic heterogeneity.
Jervell and Lange-Nielsen Syndrome
In Jervell and Lange-Nielsen syndrome, a recessively inherited, congenital SNHL is
associated with episodes of syncope caused by a cardiac conduction defect, which can
lead to sudden death. The degree of hearing loss is variable but usually severe.
Electrocardiography shows large T waves and prolongation of the QT interval, which can
cause syncope as early as the second or third year of life. The attacks of syncope can
resemble seizures. Some persons with this syndrome have received an incorrect diagnosis
of epilepsy and been treated with anticonvulsants, whereas -adrenergic blockers such as
propranalol have proved effective in managing the cardiac component of the syndrome.
Electrocardiography is performed for all children with early-onset hearing loss of
uncertain causation, particularly if there is a history of syncope or unexplained seizures or
if there is a family history of syncope or sudden death. One form of Jervell and Lange-
Nielsen syndrome has been attributed to homozygosity for mutations of a potassium
channel gene, KVLQT1. Other mutations in this gene cause the dominantly inherited long
QT syndrome (Romano-Ward syndrome). Not all families with Jervell and Lange-
Nielsen syndrome map to this gene, so genetic heterogeneity is clear. Mutations have also
have been found in another potassium channel gene, KCNE1. In some families,
heterozygous carriers of Jervell and Lange-Nielsen show a prolonged QT interval, which
can be asymptomatic.
NONSYNDROMIC RECESSIVE SENSORINEURAL HEARING LOSS
Konigsmark and Gorlin (2) divided nonsyndromic recessive SNHL into three subtypes
congenital severe-to-profound, congenital moderate, and early-onset, which usually
progresses rapidly from onset at 1 years of age to profound loss by 6 years of age.
Congenital profound SNHL is most common, and genetic heterogeneity is apparent
because the offspring of two persons with clinically identical recessive hearing loss
usually have normal hearing. Linkage studies have already identified at least 29 loci for
recessive nonsyndromic hearing loss. These genes are given the prefix DFNB. One such
gene, CX26 (also known as GJB2 or DFNB2) is the most common. It accounts for
approximately 50% of recessive nonsyndromic hearing loss. It produces a gap junction
protein called connexin 26, which forms transmembrane channels for intercellular
communication. Although the hearing loss produced by mutations in this gene is usually
stable, the degree of hearing loss can vary from mild to profound.
Some mutations are more common among specific ethnic populations; for example, 70%
of the mutations among white persons of European descent involve a deletion of one of a
string of six guanines. This deletion has been called 30delG or 35delG, depending on the
position in the gene of the presumed G that was lost. A deletion of a thymine at position
167 (167delT) is present in the Ashkenazi Jewish population, and a 235delC mutation
occurs more frequently in Asia. Among the U.S. white population, the frequency of
heterozygous carriers of mutations in CX26 is approximately 1 in 40, making it almost as
common as cystic fibrosis, which has a carrier frequency of approximately 1 in 24. The
high frequency of mutation and the small size of this gene make screening and molecular
genetic diagnosis feasible. Unlike CX26, other genes account for only one or a few inbred
families each.
SEX-LINKED DISORDERS
Sex-linked disorders are caused by genes on the X or Y chromosome. There are no
known hearing loss genes on the Y chromosome, so the disorders discussed herein are all
X linked. Although sex-linked inheritance of hearing loss is uncommon, it may constitute
approximately 6% of cases of nonsyndromic profound loss among men and boys.
Singleton cases that may represent new mutations are possible.
Norrie Syndrome
Norrie syndrome is a sex-linked disorder that comprises congenital or rapidly progressive
blindness with bilateral pseu-doglioma and exudative vitreoretinopathy, opacification,
and ocular degeneration resulting in microphthalmia. Progressive SNHL, with onset in
the second or third decade, affects approximately one third of patients with Norrie
syndrome. In some families, there also is progressive mental deterioration. The gene for
Norrie syndrome, NDP, produces a protein that has been called norrin and appears to be
a growth factor similar to transforming growth factor , which is responsible for
vasculogenesis. A number of families have variable deletions in this chromosomal
region, and deletions involving contiguous genes, particularly the monoamine oxidase
genes, may account for the finding of mental deficiency among some families. On the
other hand, mutations entirely within the NDS gene also have produced progressive
mental retardation.
Otopalatodigital Syndrome
Hypertelorism, craniofacial deformity involving the supraorbital area, flat midface, small
nose, and cleft palate are components of otopalatodigital syndrome. Affected persons are
short, have broad fingers and toes, which vary in length, and have an excessively wide
space between the first and second toes. Conductive hearing loss usually is caused by an
ossicular malformation that may be amenable to surgical intervention. Female carriers
can have mild manifestations of the disorder but to a lesser degree than affected men and
boys. The gene has been localized to Xq28.
Wildervanck Syndrome
Wildervanck syndrome comprises the Klippel-Feil malformation involving fused cervical
vertebrae, sensorineural or mixed hearing loss, and paralysis of the sixth cranial nerve,
which causes retraction of the eye on lateral gaze. The last condition also is called the
Duane retraction syndrome. The hearing loss is related to bony malformation of the inner
ear. Wildervanck syndrome is almost totally limited to women and girls, raising the
possibility of X-linked dominant inheritance or polygenic inheritance with lethality
among boys and men. Isolated Klippel-Feil sequence includes hearing loss in
approximately one third of cases, but it is rarely familial. Hearing loss also can be
associated with Duane syndrome in a small percentage of cases, less than 10%.
Alport Syndrome
Alport syndrome involves SNHL associated with renal disease of varying severity. The
hearing loss, which is progressive, may not become manifest until the second decade of
life. The nephritis, which can manifest as hematuria in infancy (red diaper), usually
remains asymptomatic for several years before the onset of renal insufficiency. The renal
component is especially severe among men and boys, often causing death of uremia
before the age of 30 years. Early diagnosis of this syndrome is essential to facilitate
management of the renal disease. Dialysis and renal transplantation have proved to be
important therapeutic advances for persons with this disorder. Alport syndrome is
genetically heterogeneous, most cases being X linked, due to mutation of a type 4
collagen gene (COL4A5). Mutation of autosomal type 4 collagen genes produces an
autosomal recessive form of Alport syndrome, but expression still is more severe among
men and boys. A similar condition with progressive hearing loss and renal disease,
Fechtner syndrome, is autosomal dominant and includes macrothrombocytopenia.
Deafness Dystonia Syndrome
Deafness dystonia syndrome is a rare X-linked neurodegenerative disorder. It involves
progressive SNHL, vision loss, including myopia and decreases in the visual field that
progress to cortical blindness, dystonia, fractures, and mental deterioration. It is caused
by mutation of a gene called DDP (dystonia-deafness protein) which on the basis of
homology appears to be involved in transport of proteins into mitochondria. This disorder
was originally described as nonsyndromic and was given the gene name DFN1, DFN
being the prefix for X-linked nonsyndromic deafness genes.
NONSYNDROMIC X-LINKED HEARING LOSS
Among five known loci on the X chromosome for nonsyndromic hearing loss is X-linked
stapes fixation with perilymphatic gusher (DFN3), which involves a progressive mixed
loss with apparent stapes fixation. Footplate surgery carries a high risk of perilymphatic
gusher and SNHL. Temporal bone imaging studies can be used preoperatively to detect
predictive findings such as an enlarged internal auditory canal with thinning or absence
of bone at the base of the cochlea. Women and girls can have mild expression of this
gene, which has been identified as the POU3F4 gene at Xq21. This gene is very close to
a gene that causes choroideremia, and deletion of these genes produces the contiguous
gene syndrome of choroideremia, hearing loss, and mental retardation. Some reports
suggest that the stapes may not be fixed but that the apparent conductive loss may be
caused by an increase in perilymphatic pressure. Because of the high risk of a gusher,
stapes surgery should be considered carefully for any young male patient, particularly
one with an X-linked family history or with choroideremia. Preoperative temporal bone
imaging, such as computed tomography, must be performed to rule out this condition.
MULTIFACTORIAL GENETIC DISORDERS
Some genetic disorders cannot be attributed to the action of a single gene but apparently
are caused by a combination of genetic factors that interact with environmental
influences. Examples associated with hearing loss include clefting (cleft lip or palate)
syndromes that involve conductive hearing loss and the microtiahemifacial microsomia
Goldenhar spectrum. In the latter, a positive family history can be elicited approximately
6% of the time, but different aspects of the spectrum can occur even within the same
family. Findings include preauricular tags or pits, vertebral anomalies such as hypoplastic
vertebrae or hemivertebrae in the cervical region, epibulbar dermoids, and coloboma of
the upper lid. Goldenhar syndrome (oculoauriculovertebral dysplasia) has been described
in some families as being inherited in an autosomal dominant pattern, but clustering in a
single family can be fortuitous. Other conditions believed to represent multifactorial
inheritance are increased susceptibility to hearing loss with diabetes and hyperlipidemia.
Whether individual variation in susceptibility to hearing loss from exposure to noise and
other prenatal and postnatal environmental insults can be attributed to multiple genetic
factors is not yet clear.
CHROMOSOMAL SYNDROMES
Down Syndrome
General developmental delay characterizes many chromosomal syndromes and
complicates evaluation of hearing and other communication skills. Middle ear and
mastoid disease often occurs among children with Down syndrome and necessitates
careful audiologic and tympanometric follow-up evaluation, but residual SNHL can be
present. Trisomy 13, which is more severe than trisomy 21, often is lethal in the newborn
period, but marked SNHL occurs among survivors.
Turner Syndrome
In Turner syndrome, monosomy for all or part of one X chromosome can be detected
initially during evaluations for delayed puberty. These girls have gonadal dysgenesis,
short stature, and often a webbed neck or shield chest. The webbed neck is caused by
cystic hygroma in utero that has resolved by birth. However, some edema of the hands
and feet may be present at birth. Sensorineural, conductive, or mixed hearing loss may be
present. The hearing loss can be progressive, and aside from the edema at birth, this can
constitute first evidence of the syndrome among prepubescent girls.
MITOCHONDRIAL INHERITANCE
Mitochondria are cytoplasmic organelles that contain small pieces of nonnuclear DNA in
a ring form. Each mitochondrion contains two to ten copies of the mitochondrial genome.
Each copy comprises approximately 16 kilobases, which contain the genes for
messenger, ribosomal, and transfer RNA needed for synthesis of mitochondrial proteins.
These proteins interact with proteins encoded by the nuclear chromosomes to facilitate
energy production through synthesis of adenosine triphosphate and oxidative
phosphorylation. Mutation in the mitochondrial genome can affect this energy
production. The result is that tissues that need high levels of energy, such as muscle, are
disproportionately affected. The mutation rate of mitochondrial DNA exceeds that of
nuclear DNA, and DNA repair mechanisms in the mitochondria are less effective.
Among hundreds of mitochondria in each cell, only a small fraction can contain a
specific mutation, a condition known as heteroplasmy, and different percentages of
mutated mitochondria can be present in different tissues. Mitochondrial diseases typically
involve progressive neuromuscular degeneration with ataxia, ophthalmoplegia, and
progressive hearing loss. In disorders with muscle involvement, results of muscle biopsy
show classic ragged red fibers. Disorders such as Kearns-Sayre, MELAS (mitochondrial
encephalopathy, lactic acidosis, and stroke), MERRF (myoclonic epilepsy with ragged
red fibers), and Lebers hereditary optic neuropathy are mitochondrial disorders.
Mutations involving hearing loss have been discovered.
Mitochondrial inheritance is distinctly different from the inheritance pattern of nuclear
genes. Because sperm transmit few or no mitochondria, nearly the entire contribution is
from the egg. The result is matrilineal inheritance that affects male and female offspring
equally. If a mother is homoplasmic for a mitochondrial mutation, all of the offspring are
affected. A condition involving diabetes, progressive hearing loss, and stroke has been
attributed to a mitochondrial deletion. A few families have nonsyndromic hearing loss
due to the combination of a mitochondrial mutation and a recessive mutation in a nuclear
gene. One such mutation involving nucleotide 1555 has been found in a large Arabic
kindred. Of greatest clinical relevance is that this mutation and at least one other
mitochondrial mutation enhance sensitivity to ototoxic effects of aminoglycosides such as
streptomycin. Milder hearing loss can be expressed among family members with these
mutations who have not yet been exposed to aminoglycosides. Screening is indicated for
maternal relatives of persons with hearing loss in response to normal therapeutic doses of
aminoglycosides. Because gradual accumulation of mitochondrial mutations in affected
tissues can worsen the phenotype over time, some authors have postulated a
mitochondrial role in presbycusis, although definitive evidence is lacking at this time.
EVALUATION AND GENETIC COUNSELING
Genetic counseling provides information to answer parents' questions about the cause of
their child's hearing loss and the inheritance pattern. The prerequisite for meaningful
counseling must be a diligent search for the cause of the hearing loss. A detailed family
history, including a pedigree chart to include third-degree relatives, is assembled.
Specific queries address the health and hearing status of other family members, who may
have subtle manifestations, such as ear pits, which can represent variable phenotypic
expression of a syndrome. Previous audiologic data acquired from the patient and other
family members are reviewed to validate the history and to determine whether familial
progressive loss is involved. It is essential to rule out consanguinity. The prenatal,
perinatal, and postnatal medical history is reviewed carefully. A thorough physical
examination is performed by a clinical geneticist-dysmorphologist to detect subtle signs
of a genetic syndrome. Depending on the history and physical findings, evaluations such
as radiographic imaging or laboratory studies may be indicated. Electroretinograms,
electrocardiograms, and perchlorate discharge studies are obtained when appropriate.
Inherited hearing loss presents a challenge to the counselor because family histories often
involve a number of marriages between deaf persons who have hearing losses of
uncertain causation. Even when deafness is clearly represented in multiple generations, it
is not unusual for family members to be unaware of its possible hereditary causation.
Family historical tradition often attributes each person's loss to a different nongenetic
cause, such as noise exposure, head trauma, or childhood infections. All reported losses,
whether or not they are initially thought to be genetic, are plotted on the pedigree, which
can then be systematically analyzed to exclude cases that are clearly nongenetic. At the
completion of an intensive and sometimes expensive evaluation, the specific cause of a
hearing loss can still be uncertain. This circumstance is frustrating for both clinicians and
parents because it limits a counselor's ability to provide information more precise than
averaged empiric estimates of recurrence risk. Even such imprecise estimates, however,
can provide reassurance to anxious parents who are confused by hearsay information
from well-meaning family members, friends, and general interest publications.
Clinicians counseling deaf couples need to be aware that the couple may not view having
a deaf child as a burden. Deaf adults are proud of their cultural heritage, unique language
(American Sign Language), and the accomplishments of deaf persons throughout history.
Sensitivity to the couple's point of view is essential, as is the availability of an interpreter,
if needed. Boughman et al. (25) developed specific signs for communicating genetic
terminology to deaf clients.
Counseling regarding the recurrence risk of autosomal dominant disorders must take into
account the degree of penetrance that usually characterizes the particular gene. If full
penetrance is the rule, the offspring of an affected person have a 50% chance of inheriting
the disorder, and children of unaffected parents are not at risk. If the gene has low
penetrance, the child of an affected parent has a 50% chance of inheriting the gene but
may not have the full phenotype. Nonpenetrance occurs in some disorders, so a
seemingly unaffected family member can transmit the gene and have an affected child.
Children of parents who are heterozygous carriers of a gene for an autosomal recessive
disorder have a 25% chance of having the disorder and a 50% chance of being a carrier.
The recurrence risk among future offspring of a child with recessively inherited deafness
depends on the genetic status of the mate. Even in deaf-deaf marriages, unless the
partners have identical genetic causes of the hearing loss, which would entail 100%
recurrence risk, the actual risk of having an affected child can be quite small.
Heterozygotic carriers of a recessive gene also have a very low recurrence risk, estimated
at approximately 1 in 100, depending on the frequency with which the specific gene
occurs among the general population. Consanguineous mating greatly increases the
recurrence risk of a recessive disorder.
Male offspring of a maternal carrier of an X-linked recessive disorder are at 50% risk of
being affected. Female offspring of the same mother have a 50% risk of being carriers.
An affected man passes the gene to all of his daughters but to none of his sons because
their X chromosome comes from their mother. The recurrence risk of multifactorial
disorders, most of which are sporadic cases, can be quite low, as can the recurrence risk
of a chromosomal disorder when both parents have normal karyo-types. The risk of a
mitochondrial disorder depends on whether the mother is homoplasmic or heteroplasmic
and whether other genetic or nongenetic factors are necessary for expression. Offspring
of a man with a mitochondrial disorder are not at risk.
Nonsyndromic hearing loss presents a special challenge. If an environmentally produced
phenotype resembling a genetic disordera phenocopyis involved, prediction of
recurrence risk is difficult. Empiric risk tables (Table 90.2) developed by Bieber and
Nance (26) provide an estimated range based on an averaged risk that accounts various
possibilities, including the number of affected and unaffected children in the family.

TABLE 90.2. RECURRENCE RISK OF
SUBSEQUENT DEAF OFFSPRING IN VARIOUS
MATINGS



The field of genetics has advanced rapidly. Research is focused on the molecular level.
The future holds the promise of effective strategies to accurately screen for, diagnose,
prevent, and ameliorate genetic hearing loss. Genetic screening raises an array of ethical
and legal issues related to confidentiality of the information. These concerns must be
addressed as scientific advances are translated to clinical practice. A practicing clinician
with an interest in childhood deafness needs to form a collaboration with a competent
geneticist or genetics center so that families can be afforded optimal care.

HIGHLIGHTS
Several population studies have estimated that 50% of cases of
childhood hearing loss are caused by genetic factors. Of these,
75% to 80% involve autosomal recessive genes; the others are
dominant and X linked.
Genetic hearing loss can be congenital or delayed in onset,
progressive or nonprogressive, unilateral or bilateral, syndromic
or nonsyndromic. Genetic hearing loss syndromes are
commonly classified according to the other organ systems
involved. Nonsyndromic hearing disorders are classified
according to audiologic characteristics, age at onset, presence
or absence of progression, and mode of inheritance.
Human genes are arranged linearly on 23 pairs of
chromosomes. One pair is called the sex chromosomes, the
others autosomes. A gene can have several alternative codes or
alleles. The genotype for a specific trait can consist of two
identical alleles (hemizygous) or two different alleles
(heterozygous).
Phenotype is determined by which alleles are present and how
they interact. A dominant allele is expressed in the homozygous
or heterozygous state, whereas an autosomal recessive allele is
expressed only in homozygotes. Recessive X-linked genes are
expressed among affected men and boys but usually not among
female carriers. Certain dominant genes have lack of penetrance
and variable expressivity, even within the same family.
Heritable disorders also can be caused by abnormalities at the
chromosomal level.
Precise chromosomal location of a specific gene is determined
through linkage analysis studies involving the phenomenon of
crossover during cell mitosis. Genetic loci are linked when their
alleles are transmitted together more often than expected by
chance.
Hearing loss can be associated with structural malformations of
the inner ear, including Michel aplasia, Mondini aplasia,
Scheibe aplasia, Alexander aplasia, and enlarged vestibular
aqueduct.
Autosomal dominant disorders involving hearing loss include
Waardenburg syndrome, Stickler syndrome, branchiootorenal
syndrome, Treacher Collins syndrome, neurofibromatosis,
otosclerosis, and at least four varieties of nonsyndromic hearing
loss.
Approximately 50% of all cases of autosomal recessive hearing
loss represent recognizable syndromes, but identification
requires a diligent search for other syndromic components.
Autosomal recessive disorders involving hearing loss include
Usher syndrome, Pendred syndrome, Jervell and Lange-Nielsen
syndrome, and at least three subtypes of nonsyndromic hearing
loss. Mutation of the Cx26 gene (connexin 26) causes as many
as 50% of cases of recessive nonsyndromic hearing loss.
Major X-linked disorders that include hearing loss are Norrie
syndrome, otopalatodigital syndrome, Wildervanck syndrome,
Alport syndrome, and several types of nonsyndromic congenital
severe SNHL. Examples of multifactorial inheritance are
clefting syndromes and the microtiahemifacial microsomia
Goldenhar spectrum.
Counseling about genetic hearing loss is complex because
family histories often involve a number of marriages between
deaf persons with hearing losses of uncertain causation.
Empiric risk tables are useful for providing an estimated range
of recurrence risk among families with nonsyndromic hearing
loss.
Ethical and legal issues regarding privacy and confidentiality
must be addressed as genetic advances are translated into
clinical practice.
CHAPTER REFERENCES
1. Jackler RK, DeLaCruz A. The large vestibular aqueduct syndrome. Laryngoscope 1989;99:1238
1242.
2. Konigsmark, Gorlin. 1976;
3. Barker DF, Hostikka SL, Zhou J, et al. Identification of mutations in the COL4A5 collagen gene
in Alport syndrome. Science 1990;248:12241227.
4. Mochizuki T, Lemmink HH, Mariyama M, et al. Identification of mutation in the alpha3(IV) and
alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. Nat Genet 1994;8:7781.
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underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nat Genet
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6. Neyroud N, Tesson F, Denjoy I, et al. A novel mutation in the potassium channel gene KVLQT1
causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nat Genet 1997;15:186189.
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syndrome. Nat Genet 1997;17:267268.
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10. Chen ZY, Hendriks RW, Jobling MW, et al. Isolation and characterization of a candidate gene for
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11. Everett LA, Glasser B, Beck JC, et al. Pendred syndrome is caused by mutations in a putative
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IVS17 characterizes the COL2A1 gene mutation in the original Stickler syndrome kindred. Am J
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13. Vikkula M, Mariman EC, Lui VC, et al. Autosomal dominant and recessive
osteochondrodysplasias associated with the COL11A2 locus. Cell 1995;80:431437.
14. Richards AJ, Yates JR, Williams R, et al. A family with Stickler syndrome type 2 has a mutation
in the COL11A1 gene resulting in the substitution of glycine 97 by valine in alpha 1 (XI) collagen.
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15. Dixon J, Edwards SJ, Galdwin AJ, et al. Positional cloning of a gene involved in the pathogenesis
of Treacher Collins syndrome. Nat Genet 1996;12:130136.
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and mutations in the POU domain gene POU3F4. Science 1995;267:685688.
Grifa A, Wagner CA, D'Ambrosio L, et al. Mutations in GJB6 cause nonsyndromic autosomal dominant
deafness at DFNA3 locus. Nat Genet 1999;23:1618.
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deafness (DFN-1), dystonia, mental deficiency and blindness. Nat Genet 1996;14:177180.
Kelsell DP, Dunlop J, Stevens HP, et al. Connexin 26 mutations in hereditary non-syndromic sensorineural
deafness. Nature 1997;387:8083.
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outer hair cells, is mutated in dominant deafness. Cell 1999;96:437446.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

91 PEDIATRIC AUDIOLOGY
Head & Neck SurgeryOtolaryngology
91




PEDIATRIC AUDIOLOGY
DEBORAH L. CARLSON
HILARY L. REEH

D.L. Carlson and H.L. Reeh: Center for Audiology and Speech Pathology, The University of Texas
Medical Branch, Galveston, Texas.


Development of Auditory Behavior
Hearing Screening
Infant Screening
School Screening
Behavioral Audiometric Assessment
General Test Considerations
Test Battery
Behavioral Test Techniques
Behavioral Observation Audiometry
Visual Reinforcement Audiometry
Conditioned Play Audiometry
Special Tests
Auditory Brainstem Response Testing
Otoacoustic Emission Testing
Reviewing Test Results
Management of Hearing Loss
Amplification
Assistive Devices
The Otolaryngologist's Role in the Rehabilitation Process
Central Auditory Processing Disorders
Definition of Central Auditory Processing Disorder
Central Auditory Processing Disorder Testing
Management of CAPD
Conclusions
Chapter References
Hearing loss among children has consequences related to speech, language, and
cognitive, educational, and social development. Fifteen of every 1,000 persons younger
than 18 years have some type of hearing loss (1). Two to three children in 1,000 have
early onset sensorineural hearing loss (SNHL) severe enough to impede normal language
acquisition. Even with special education, one half of these children attain only a fourth
grade level of education by the time they graduate from high school (2). Early diagnosis,
intervention, and a collaborative approach to management are essential elements in the
care of pediatric patients with hearing loss. The otolaryngologist and audiologist maintain
a close working relationship with respect to diagnosis and ongoing treatment of patients
with hearing loss.
DEVELOPMENT OF AUDITORY BEHAVIOR
Development of auditory behavior begins gestationally with the embryologic
development of anatomic structures and continues through adolescence with the
maturation of the central auditory nervous system (CANS) (see Chapter 128). From a
sensory standpoint, the infant is prepared to respond to sound at birth. Signs of complex
processing, including recognition of the mother's voice and differentiating voiced and
voiceless sounds, have been demonstrated in early infancy. However in response to
normal developmental patterns, the level of sound necessary to elicit an infant response
decreases over the first 12 months of life (3).
Initial infant responses to sound are reflexive, such as startle or cessation of activity. As
infants mature cognitively and gain motor control, they begin to develop sound
localization in horizontal and then vertical planes. Eventually, infants show increased
interest and interactive responses to oral commands. Complex or broadband stimuli are
more effective than pure tones or other narrow-band signals in eliciting infant responses
to sound. With the help of the appropriate test technique, complex stimuli elicit relatively
normal threshold levels. On the other hand, responses to pure-tone stimuli initially appear
elevated and reach adult threshold levels by 6 months of age. The development of these
responses improves pure-tone thresholds as much as 30 dB at 4,000 Hz and 15 dB for
low frequencies.
For the purposes of auditory testing and rehabilitation, it is important to keep in mind that
some anatomic changes continue after birth. For example, the outer ear continues to grow
throughout childhood. The bony portion of the external auditory canal alters shape
through 7 years of age, and the pinna grows until about 9 years of age. The primary
postnatal change in the middle ear is a positional change of the tympanic membrane. The
cochlea is the same size it is in an adult and can respond to sound by gestational week 24
(4).
The CANS continues to develop well into adolescence. Brainstem myelinization usually
is complete by 1 year of age. Cerebral structures have complete myelinization at 10 years
or older. Continued maturation relates to the anatomic development of dendritic
branching and formation of the neural synapse sites (5). These continued physiologic
changes enhance the efficiency of the CANS in handling auditory information. Likewise,
sensory deprivation causes cell death or functional changes that affect the efficiency of
the CANS. The effects of postnatal anatomic and developmental changes must be
considered in the selection and interpretation of auditory test techniques and
rehabilitative strategies. The influence of these issues is discussed with specific test
techniques and considerations in fitting of amplification devices (see later).
HEARING SCREENING
Infant Screening
Assessment of hearing should begin at birth. The prevalence of moderate or greater
SNHL is estimated to be approximately 6 cases per 1,000 livebirths. The prevalence of
profound SNHL is estimated to be 1 case among 1,000 well infants (6). Once a child is
referred after screening, a comprehensive audiologic assessment must be pursued
immediately so that appropriate medical, habilitative, and educational referrals can be
made.
In 1990, the U.S. Department of Health and Human Services estimated the average age
for detection of hearing loss to be 2.5 years in the United States as opposed to
approximately 7 months in the United Kingdom. The Department of Health and Human
Services declared the goal of reducing the age at identification of hearing loss to less than
12 months by the year 2000 (7). Five years later, Stein (8) suggested that the actual age of
identification depends greatly on the degree of hearing loss. His estimates showed a mean
or median age of identification for severe to profound congenital hearing loss ranging
from less than 6 months to 18 months. It appears that infants who have received care in a
neonatal intensive care unit and those who have been found to be at risk for hearing loss
have an average age at identification closer to 12 months (8). In a carefully controlled
study, Yoshinaga-Itano (9) showed some normal language levels for babies receiving
early identification and intervention. Children with a profound hearing loss had language
skills as high as children with very mild hearing loss when intervention began before 6
months of age.
Guidelines for the detection of hearing loss among infants have been provided by the
multidisciplinary Joint Committee on Infant Hearing (10). The committee endorses
universal detection of infant hearing loss by 3 months of age and intervention by 6
months of age. Table 91.1 describes the risk indicators associated with hearing loss
among neonates and infants. Although these indicators help to identify hearing loss,
about 50% of infants with marked congenital hearing loss do not have any risk indicators
(11). Approximately two of three infants with hearing loss do not need the specialized
care of a neonatal intensive care unit (12).

TABLE 91.1. YEAR 2000 JOINT COMMITTEE ON
INFANT HEARING RECOMMENDATIONS FOR
INDICATORS ASSOCIATED WITH
SENSORINEURAL OR CONDUCTIVE HEARING
LOSS AMONG CHILDREN



In addition to early identification and intervention, the committee (10) emphasized the
importance of periodic examination of infants to detect delayed-onset hearing loss.
Children with indicators of progressive or delayed-onset hearing loss (Table 91.1) should
be examined a minimum of once every 6 months through 3 years of age, the critical time
for speech and language development. Beyond the 3-year period, monitoring of hearing
should occur on an as-needed basis, with prime consideration given to parental concerns
regarding hearing.
In 1993, a National Institutes of Health consensus panel on early identification of hearing
loss among infants and young children focused its efforts on identifying the necessity,
method, models, and future research needs pertaining to infant hearing screening (13).
The panel endorsed the need for universal screening before the infant is discharged from
the hospital. The panel further recommended (a) a two-stage screening process
combining the use of otoacoustic emissions (OAE) and auditory brainstem response
(ABR) testing; (b) the need for comprehensive intervention and management programs;
(c) continued monitoring for hearing loss throughout infancy and early childhood; and (d)
education of primary caregivers and health care providers on early signs of hearing loss.
As of April 2001, 32 states had legislative mandates for universal infant hearing
screening.
The use of ABR testing for infant hearing screening has been well accepted. Automated
ABR techniques have an average sensitivity of 98% and a specificity of 96% (14). The
ABR is most commonly elicited by a click stimulus at intensity levels between 30 and 40
dBnHL. When ABR is used to describe hearing sensitivity, the results yield an estimate
of hearing limited to the frequency range of 1,000 to 4,000 Hz. Because of the continued
maturation of the CANS, interpretation of either a threshold or a neurologic ABR
procedure must be related to age-specific norms.
Otoacoustic emissions testing also is used for infant screening. Its popularity for
screening is based on the fact that it is a noninvasive measure of cochlear (outer hair cell)
function and thus is representative of peripheral hearing. Otoacoustic emissions tests are
independent of neural and central auditory system effects, can be relatively low cost to
administer, and can be performed over a relatively broad, frequency-specific range (1,000
to 6,000 Hz). Unlike the ABR, OAE amplitudes are more robust at birth than in
adulthood.
Transient evoked otoacoustic emissions (TEOAEs) are used in the most common OAE
screening test of infants (15), although distortion product otoacoustic emissions
(DPOAEs) tests continue to increase in popularity. Transient evoked oto-acoustic
emissions are reported to have excellent sensitivity (90% to 100%), with specificity in the
range of 82% to 84% (16). Initial failure rates for OAE screening vary considerably;
reports range from 10% to 40% (17). Factors that influence the success of OAE testing
include the noise level in the test environment, vernix in the external auditory meatus,
middle-ear dysfunction, and reduced responses for very low-birth-weight or premature
infants.
School Screening
Identification of hearing loss continues well into childhood. Most states require hearing
screening throughout grade school (preschool, kindergarten, and first, third, fifth,
seventh, and ninth grades). The primary goal of these screenings is to identify hearing
losses that may interfere with communication and therefore with education. The most
common and reasonably accessible means of screening is pure-tone air-conduction
audiometry.
Guidelines for educational screening frequently are defined by the state health
department. The American Speech-Language-Hearing Association recommends
screening at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz at levels of 20 dBHL. Because
screenings are not conducted in acoustically controlled environments, it is essential to
confirm that ambient noise levels do not exceed 41.5 dBA. If pure-tone screening is
supplemented with immittance screening, 500 Hz can be eliminated, and ambient noise
levels can be extended to 49.5 dBA or lower. With this procedure, failure to respond to
any tone in either ear necessitates rescreening. Failures on rescreenings necessitate full
audiometric evaluation (18).
BEHAVIORAL AUDIOMETRIC ASSESSMENT
General Test Considerations
Full audiometric evaluation is recommended after failure of a screening test or referral
because of screening results. Although ABR and OAE measures can be used for
assessment of the hearing of children younger than 5 months, behavioral testing is the
first method used to test children who are at least 5 months of age. The goal of behavioral
audiometric assessment is to establish hearing levels for each ear. The degree and nature
of the hearing loss must be determined to provide evidence for medical or surgical
diagnosis and treatment, appropriate selection of amplification or other rehabilitative
measures, and establishing a baseline for continued monitoring of auditory function. The
audiologist approaches this goal with a complete knowledge of auditory maturational
processes, developmental milestones, and a variety of test stimuli and techniques. Testing
often is completed over several test sessions. The initial testing session should provide
information about the possibility of normal hearing, conductive or hearing loss
necessitating immediate medical attention, permanent SNHL necessitating medical
follow-up therapy, and the schedule for continued audiologic follow-up care.
Test Battery
A pediatric audiologist relies on a battery of tests and professional observations to
diagnose and habilitate hearing loss. Assessment includes observation of the child's
behavior, case history, determination of developmental age, cursory otoscopic
examination, tympanometry, assessment of acoustic reflexes, and behavioral audiometric
testing (air conduction and bone conduction) to both speech and frequency specific
stimuli. Information obtained from each step of the assessment assists the audiologist in
establishing the selection and sequence of tests.
Clearly established priorities and continued flexibility in test selection are essential to
maximize the amount of diagnostic information obtained. For example, referral for ABR
testing should be secondary to attempts at behavioral testing of the young child. Only
after behavioral methods are deemed unsuccessful or leave doubt about estimated hearing
levels is referral for ABR testing indicated.
Immittance Testing
Immittance testing yields information about middle-ear function and is attempted early in
the test battery. Ear canal volume, tympanometric findings, and acoustic reflex levels
provide objective information about the nature of the hearing loss. Because of the
continued growth of the external auditory meatus, the volume of the ear canal of children
(0.5 to 1.0 cc) is smaller than that of adults (0.6 cc to 2.0 cc).
Tympanographic classifications and acoustic reflex data on infants at least 4 months of
age are interpreted in the same manner as those on adults. The findings for infants
however, must be interpreted with caution. Among children younger than 4 months, the
tympanometric findings may be influenced by developmental factors, including
incomplete ossification of the canal wall, which increases volume and compliance, and
unresolved mesenchyme in the middle ear, which increases resistance (19). The influence
of physiologic development on tympanometric and acoustic reflex data may be less
apparent when a high-frequency (660 Hz) probe tone is used.
Speech Testing
Behavioral audiometric testing typically begins with speech stimulation to provide an
overall idea of how the child is responding and a reference for frequency-specific testing.
The broadband speech signal is more interesting and meaningful to a child and usually
can be obtained at lower thresholds than can frequency-specific stimuli.
For infants and toddlers, a speech awareness threshold is obtained. The speech awareness
threshold is the softest level at which the child responds to the presence of speech. The
speech awareness threshold is obtained at a level approximately 10 dB below a speech
reception threshold by means of a picture pointing task. Once the child is talking
intelligibly, standard speech reception threshold procedures can be used. The speech
reception threshold or speech awareness threshold is elicited using both air- and bone-
conduction stimuli.
Assessment of speech recognition among children usually is not attempted until the child
reaches a developmental age of 3 years or more. Because of the short attention span of
many young children, this task is the lowest priority in the test battery and is deferred
until attempts have been made to obtain frequency-specific information. Closed-set word
recognition tasks can be performed with picture identification tasks, such as the
Northwestern University Children's Perception of Speech (NU-CHIPS), Word
Identification by Picture Identification (WIPI), or Pediatric Sentence Identification (PSI)
test.
Pure-tone Testing
The main goal in the behavioral test battery is to obtain ear- and frequency-specific
thresholds. This is accomplished with warble tones in a sound field or with pure tones
when insert or traditional earphones are used as tolerated by the child. The initial test
frequency is 2,000 Hz, which complements the low-frequency information obtained in
the speech awareness thresholdspeech reception threshold procedure and is more likely
to reflect SNHL. The 2,000-Hz signal usually is followed by a 500-Hz signal, which
commonly is affected in conductive hearing loss. Other octave frequencies are presented
as tolerated by the attention span of the child.
BEHAVIORAL TEST TECHNIQUES
Behavioral testing is conducted in a sound-treated room. Stimuli are presented with one
or more transducer types, including sound-field speakers, air (insert earphones or
headphones), and bone conduction transducers. Because insert earphones are small and
lightweight, information about the separate ears often is available for young children.
Three test techniques are used to obtain behavioral response levels from a child
behavioral observation audiometry, visual reinforcement audiometry, and play
audiometry. These techniques provide varying estimates of hearing levels according to
the developmental age of the child. Air conduction, bone conduction, and speech
threshold responses can be obtained with these techniques.
Behavioral Observation Audiometry
Behavioral observation audiometry relies on reflexive responses and state changes. It is
reserved for very young infants or children with developmental delay (those who function
at a developmental level younger than 5 months of age). The unconditioned responses
obtained with behavioral observation audiometry are variable and imprecise, habituate
rapidly, are influenced by stimulus type, and most often are obtained by biased observers.
Diagnosis never depends solely on these results. Because standard threshold techniques
are not possible with behavioral observation audiometry, responses are reported as
minimal response levels and are not considered true thresholds.
Visual Reinforcement Audiometry
By the time a child has reached the developmental age of 5 months, an audiologist can
receive better audiometric information by means of visual reinforcement audiometry.
Visual reinforcement audiometry is an operant conditioning paradigm in which the child
turns naturally or is trained to look for an auditory stimulus. This behavior is reinforced
with a flashing light or animated toy. With the use of varied types of reinforcement, the
child's interest is held and the head-turn response is kept from quickly extinguishing. In
most cases, this procedure allows use of a standard threshold technique to obtain hearing
levels. The head-turn response can be especially useful in a sound-field environment, in
which localization preferences suggest possible ear differences. With immittance and
unmasked bone conduction responses, a localization preference can provide information
similar to that obtained with an audiometric Weber test.
Conditioned Play Audiometry
Once his or her developmental age reaches 2 years, a child can be taught to respond to a
stimulus by means of conditioned play audiometry. In play audiometry (Fig. 91.1), the
child is trained to perform an activity, such as stacking rings or dropping a block in a
bucket, in response to an auditory stimulus. The task is presented as a play activity and
can be changed to maintain the child's interest. The standard threshold technique can be
used, and normal adult threshold levels are expected. By a developmental age of 5 years,
standard adult testing techniques can be used in audiometric assessment. However, the
audiologist must remain flexible in implementing and reverting to any of the behavioral
pediatric test techniques. This flexibility maximizes the amount of information obtained
and applied to a definitive diagnosis of hearing loss.

FIGURE 91.1. Conditioned play audiometry.



SPECIAL TESTS
Auditory Brainstem Response Testing
When behavioral testing does not provide definitive data or when hearing levels remain
in doubt, ABR testing can be performed. The ABR can provide a threshold estimate of
hearing in the 1,000 to 4,000 Hz range for young children or those who are difficult to
test. With the additional use of a 500-Hz tone burst stimulus, low-frequency hearing
sensitivity can be estimated. A bone-conducted stimulus can help define the nature of the
hearing loss. The limitations of bone-conducted ABR testing are beyond the scope of this
chapter but can be found elsewhere (20).
The ABR follows neuromaturation of the CANS. It reaches adult levels by 3 years of age.
The newborn ABR comprises primarily waves I, III, and V. Wave V has a smaller
amplitude than the same adult waveform. Wave I of the ABR reaches adult latency by 3
months of age. Wave V has a rapid latency decrease over the first 3 months of life and
continues to change gradually over the next 2 to 3 years (5).
The ABR is best obtained with the child in a natural sleep state, which can be
accomplished through counseling families regarding sleep deprivation or feeding the
child before the test. When natural sleep is not possible, conscious sedation with chloral
hydrate or midazolam can be used. The use of sedation must be recommended and
supervised by a physician, and nursing support for conscious sedation must be available
throughout the test session. Interpretation of the ABR must be based on the maturational
issues described earlier.
Otoacoustic Emission Testing
As an objective measure, OAE testing provides information regarding estimates of
functional hearing. Results are interpreted in terms of the presence of cochlear function in
a defined frequency region as opposed to estimates of sensitivity thresholds (see earlier
and Chapter 132).
REVIEWING TEST RESULTS
Audiometric data are reviewed as a total test battery. Results of each test are compared to
ensure an estimate of both hearing and test reliability. The more objective results of
immittance testing support behavioral test results in differentiating the nature of the
hearing loss. This is particularly important for the difficult-to-test population, whose
behavioral responses often are poor, and objective test measures predominate. For
example, the absence of behavioral responses to sound suggests a hearing loss; however,
the added presence of normal acoustic reflex levels suggests the potential for normal
auditory function and warrants further observation and assessment. In reviewing of
behavioral audiometric data on children, chronologic age and developmental status are
references. If the developmental level is younger than 5 months of age, results are viewed
as minimal response levels as opposed to a representation of true thresholds.
The behavioral test results of the 6-month-old infant in Fig. 91.2 fall just outside the
range considered normal for adults (0 to 25 dB). Tympanograms show normal pressure-
compliance curves (type A) with intact acoustic reflexes at normal levels. Given a birth
history of 2 months' prematurity and no parental concern about hearing, the audiologist
considers the behavioral responses within normal limits. This interpretation is based on
the child's developmental level as opposed to chronologic age. Continued care of this
patient includes behavioral testing in 1 to 2 months to follow the child's developmental
progress. A range of 0 to 15 dB is considered normal for children from approximately 5
months of age through early elementary grades (a critical period for the development of
speech, language, and cognitive skills). A different interpretation of the audiogram in Fig.
91.2 applies for a normally developing 1-year-old child. In such a case, a mild hearing
loss is suspected and behavioral testing is repeated.

FIGURE 91.2. Example of pediatric audiometric test
results.



Interpretation of test results among the young pediatric population is highly
individualized. Although the basic description of hearing loss is similar to that for adults,
the handicapping effects of hearing loss on developing communication skills differs from
that among the adult population. Table 91.2 shows the potentially handicapping effects of
varying degrees of hearing loss on a child's speech and language development. The
implications of the hearing loss in an educational setting also are provided. This
information is important in determining the appropriate management of the hearing loss.

TABLE 91.2. HANDICAPPING EFFECTS OF
HEARING LOSS AMONG CHILDREN



MANAGEMENT OF HEARING LOSS
Amplification
Children who are developing speech and language skills need to hear sounds consistently
to model speech and develop adult listening skills, such as understanding speech in
context and being able to fill in the blanks when listening situations are not ideal. Figure
91.3 shows the speech spectrum. At average conversational levels, the unvoiced
consonants: s, p, k, th, f, and sh fall at or below normal adult hearing levels. Better
hearing is needed for more consistent detection of these sounds. This is the reason for a
critical range of hearing of 0 to 15 dB for a young child.

FIGURE 91.3. Audiogram of familiar sounds.



Amplification as a rehabilitative technique in addressing an educationally significant
hearing loss relies on complete and accurate testing and is further complicated by the
need for early intervention. For very young children, obtaining hearing thresholds and
selecting appropriate amplification are ongoing processes. Hearing aids that provide
maximum flexibility in output, gain, and frequency response are desired. Because of the
small and changing size of the ear canal, selection of hearing aid output necessitates close
attention and continued monitoring. Output sound pressure levels are reported by
manufacturer specifications at levels relative to a simulated adult ear canal (2-cc coupler).
When output levels are measured in the small ear canal of a child, the sound pressure
levels can be 15 to 20 dB higher than those indicated by manufacturer specifications.
Also owing to the smaller size of the concha and shorter ear canal, the resonance
frequency of the infant ear canal is much higher (7,200 Hz) than the typical adult
resonant frequency of approximately 2,700 Hz (21). These changes affect selection of
gain and peak frequency responses. Because resonant frequency rapidly decreases until
24 months of age, when it approximates adult values, continued monitoring of hearing
aid gain is necessary. Real ear measurements with probe microphone technology and
prescriptive fitting approaches, such as desired sensation level (22), are effective in
monitoring these effects and preventing discomfort or overamplification.
Other considerations in pediatric hearing aid fittings include the type of fitting and style
of hearing aid. The benefits of binaural amplification are well documented. The effects of
auditory deprivation have been demonstrated among children as well as in adults. In a
retrospective study involving children with bilateral, moderate, early onset SNHL,
Gelfand and Silman (23) found a statistically significant decrease in speech recognition
scores in the unaided ears of children who had monaural hearing aid fittings. No
significant speech recognition differences were found in the aided ears of monaural
fittings or between those of binaural fittings. Thus binaural hearing aids are fit whenever
residual hearing is apparent or until continued testing proves this to be detrimental or of
no measurable benefit.
The best style for children usually is a behind-the-ear hearing aid. The need for the use of
body-worn instruments in most cases has been abolished as technologic advances in
instrumentation have been made. An in-the-ear hearing aid is not usually recommended
for infants or children because of its size, limited flexibility of components, need for
frequent recasing, and durability. As for adults, the ear-mold style for use with a behind-
the-ear hearing aid depends on the degree and configuration of the hearing loss. A soft
ear-mold material is used for safety and feedback control. Continued monitoring and
frequent replacement of ear molds are common because the ear canal and pinna continue
to grow until approximately 9 years of age. At that point, an in-the-ear or in-the-canal
hearing aid may be preferable.
Bone-conduction hearing aids may be appropriate when air-conduction hearing aids do
not fulfill the amplification needs for conductive hearing losses. Such cases include
atretic or microtic ears, chronic drainage from middle-ear problems, and abnormally
small ear canals. Because of the low-fidelity sound produced by bone oscillators,
problems in maintaining proper placement and the cumbersome nature of the bone-
conducted hearing-aid system, these aids are considered only when more traditional
forms of amplification are not possible.
Assistive Devices
Beyond traditional amplification, there are other options to maximize the benefit from
amplification. Personal or classroom FM systems often are used to decrease the signal-to-
noise ratio, reverberation, and distance problems that degrade the signal received by the
hearing aid. The FM system addresses these problems with a remote microphone at the
target stimulus, such as the teacher's voice or video system, that broadcasts the response
to a receiver worn by the hearing-aid user.
For children who do not benefit from in-depth trials with traditional amplification, there
are personal hearing instruments such as frequency transposition aids and tactile devices.
The surgical alternative of cochlear implantation also may benefit these children (24).
THE OTOLARYNGOLOGIST'S ROLE IN THE REHABILITATION
PROCESS
The otolaryngologist's role in the amplification process is to provide medical evaluation
of the hearing loss and clearance for the use of a hearing aid. The U.S. Food and Drug
Administration requires medical clearance within 6 months of fitting for children younger
than 18 years who wear a hearing aid. Many states also require a physician's statement
indicating the effect of existing hearing loss on a child's educational performance before
the child's enrollment in special education services under the federal Individuals with
Disabilities Education Act of 1990. Otologic monitoring of middle-ear status also is
important in a child fit with amplification. The typical threshold changes of 20 to 40 dB
that accompany middle-ear effusion can greatly affect the benefit a child receives from a
hearing aid. The small size of the pediatric ear canal necessitates periodic monitoring for
excessive cerumen. Excessive, but nonoccluding, cerumen can be troublesome when the
receiver tubing of the hearing aid rests against or is aimed directly at the cerumen.
CENTRAL AUDITORY PROCESSING DISORDERS
The test battery discussed earlier is important in diagnosing peripheral hearing
impairment or sensitivity loss. Many children, however, arrive in the physician's office
with symptoms of hearing loss, learning problems, and attention problems unrelated to
hearing loss. Despite normal hearing, these children typically fail a school hearing
screening or parents relate that the child does not hear properly. Children with these
concerns often have a central auditory processing disorder (CAPD).
Definition of Central Auditory Processing Disorder
As defined by an American Speech-Language-Hearing Association ad hoc committee,
CAPD is a . . . deficit in the information processing of audible signals not attributed to
impaired peripheral hearing sensitivity or intellectual impairment . . . . CAPD refers to
limitations in the ongoing transmission, analysis, organization, transformation,
elaboration, storage, retrieval, and use of information contained in audible signals (25).
In nontechnical terms, central auditory processing relates to what the brain does with the
auditory signal. This involves processes of signal reception, perception, and ultimately
understanding. Signs of CAPD are provided in Table 91.3. These difficulties are similar
to those of a child with attention deficit disorder. Unlike attention deficit disorder,
however, CAPD has an auditory basis. A central auditory processing disorder can exist
by itself or, more commonly, exist with language, learning, or attention deficits.

TABLE 91.3. SIGNS OF CENTRAL AUDITORY
PROCESSING DISORDER



Central Auditory Processing Disorder Testing
The goal of CAPD testing is to evaluate the integrity of the CANS and to quantify and
qualify the types of difficulties encountered. Because the CANS is an internally
redundant systemthat is, it has multiple pathwaysCAPD testing is accomplished
through control of external redundancy (test stimulus). The redundancy of the test
stimulus is manipulated by means of a presentation format (monaural, binaural, dichotic)
and signal redundancy (frequency, intensity, time alterations). Table 91.4 shows a variety
of CAPD tests used in the evaluation of children. The test battery consists of both
behavioral and electrophysiologic components and usually is given to children ages 6
years and older. The behavioral component is composed of a selection of tasks that yield
information about the amount and types of auditory difficulties a child experiences.

TABLE 91.4. TESTS COMMONLY USED TO
DIAGNOSE CENTRAL AUDITORY PROCESSING
DISORDER AMONG CHILDREN



Electrophysiologic testing further defines the adequacy and maturation of the central
auditory pathways. The ABR, middle latency response, and late vertex response are
exogenous evoked potentials, which are elicited by an external event such as an auditory
stimulus. They reflect function of the CANS from the distal end of the eighth cranial
nerve through the auditory cortex. The P300 is an endogenous evoked potential, which is
elicited by an internal event such as perception or cognition. It is used to evaluate
cortical-level processing functions. Contralateral suppression of OAEs is a promising
contribution to the CAPD test battery.
Management of CAPD
Once CAPD is diagnosed, management must be consid-ered. Environmental
modifications, such as preferential seating, acoustic modifications, and increased visual
cues, and compensatory strategies, such as cueing, repetition, review, listening breaks,
musician earplugs, and tape recorded lectures, are commonly suggested. Other
management strategies include direct remediation to address skills such as auditory
memory or perceptual training, metalinguistics, metacognition, noise desensiti-zation,
highlighting, and neural retraining. Amplification with personal or classroom style FM
systems can be helpful in compensating for the inefficient CANS. Benefits of FM
systems include improved signal-to-noise ratio, uniform intensity of speaker's voice, and
preservation of a wideband frequency re-sponse. Because most children with a CAPD
have normal hearing sensitivity, it is essential to take precautions in fitting personal
amplification systems. Output should not exceed 105 dBSPL (FM systems for students
with hearing loss have output levels of 145 dBSPL). Attenuated headsets are available for
these needs.
CONCLUSIONS
The diagnosis and management of hearing loss among children represent a collaborative
effort among the otolaryngologist, audiologist, primary care physician, and educational
personnel. Queries about hearing risk indicators, observation of communication skills,
and parental reports about speech-language development and listening behaviors should
be frequent and occur during all office visits. Parental concerns about hearing are good
indicators of hearing loss and should result in immediate referral for medical and
audiologic assessment. Early and ongoing diagnosis of peripheral and central auditory
disorders leads to effective management and increases the quality of life for children with
hearing loss.

HIGHLIGHTS
Fifteen of every 1,000 children younger than 18 years have
some type of hearing loss.
The development of the auditory system begins with
embryological development and continues through adolescence
with the maturation of the CANS.
Identification of hearing loss among children begins at birth and
can be accomplished with the use of high-risk indicators, ABR,
and OAE testing.
Approximately 50% of infants with substantial congenital
hearing loss do not have indicators of high risk.
Behavioral audiometric threshold testing of infants may begin
as early as 5 months of age.
Auditory brainstem response threshold testing provides an
estimate of hearing sensitivity in the 1,000 to 4,000 Hz range.
Interpretation of the pediatric audiometric test battery requires
knowledge of the child's developmental level, limitations of the
tests used, and disabling effects of the hearing loss.
The use of amplification by children is an ongoing process and
necessitates frequent monitoring and fitting adjustments.
Children with normal hearing who have symptoms of hearing
loss may have a CAPD.
The diagnosis and management of hearing loss among children
represent an ongoing and collaborative effort among the
otolaryngologist, audiologist, primary care physician, and
educational personnel.
CHAPTER REFERENCES
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and Health Statistics Series. Vol. 10. Hyattsville, MD: National Center for Health Statistics,
1994:190.
2. Decade of the brain: answers through scientific research. Bethesda, MD: National Advisory
Neurological and Communicative Disorders and Stroke Council; 1989. NIH publication 88-2957.
3. Nozza RJ, Wilson WR. Masked and unmasked pure-tone thresholds of infants and adults:
development of auditory frequency selectivity and sensitivity. J Speech Hear Res 1984;27:613
622.
4. Peck JE. Development of hearing, III: postnatal development. J Am Acad Audiol 1995;6:113123.
5. Musiek FE, Verkest SB, Gollegly KM. Effects of neuromaturation on auditory evoked potentials.
Semin Hear 1988;9:113.
6. Northern JL, Hayes D. Universal screening for infant hearing impairment: necessary, beneficial
and justifiable. Audiol Today 1994;6:1013.
7. US Department of Health and Human Services, Public Health Service. Healthy people 2000.
DHHS publication PHS 91-50213. Washington, DC: US Government Printing Office, 1990.
8. Stein LK. Commentary on the real age of identification of congenital hearing loss. Audiol Today
1995;7:1011.
9. Yoshinaga-Itano C. Efficacy of early identification and early intervention. Semin Hear
1995;16:115123.
10. Joint Committee on Infant Hearing. Year 2000 position statement. Rockville, MD: ASHA, 2000.
11. Mauk GW, White KR, Mortensen LB, et al. The effectiveness of screening programs based on
high-risk characteristics in early identification of hearing impairment. Ear Hear 1991;12:312319.
12. Stein LK, Jabaley T, Spitz R, et al. The hearing impaired infant: patterns of identification and
habilitation revisited. Ear Hear 1990;11:201205.
13. Early identification of hearing impairment in infants and young children. NIH Consensus
Statement. Bethesda, MD: National Institutes of Health, 1993;124.
14. Herrmann BS, Thornton AR, Joseph JM. Automated infant hearing screening using the ABR:
development and validation. Am J Audiol 1995;4:614.
15. White KR. Universal newborn hearing screening using transient evoked otoacoustic emissions:
past, present and future. Semin Hear 1996;17:171183.
16. White KR. Practicality, validity, and cost-efficiency of universal newborn hearing screening using
evoked otoacoustic emissions. In: Program and abstracts of the NIH Consensus Development
Conference, Bethesda, Maryland. Bethesda, MD: National Institutes of Health, 1993:115118.
17. Jacobson JT, Jacobson CA. The effects of noise in transient EOAE newborn hearing screening. Int
J Pediatr Otorhinolaryngol 1994;29:235248.
18. American Speech-Language-Hearing Association. Guidelines for identification audiometry.
Rockville, MD: ASHA, 1985:4953.
19. Margolis RH, Shanks JE. Tympanometry: basic principles and clinical applications. In:
Rintelmann RF, ed. Hearing assessment, 2nd ed. Austin, TX: Pro-ed, 1991:179245.
20. Hall JW III. Handbook of auditory evoked responses. Needham Heights, MA: Allyn & Bacon,
1992.
21. Hawkins DB, Northern JL. Probe microphone measurements with children. In: Mueller HG,
Hawkins DB, Northern JL, eds. Probe microphone measurements: hearing aid selection and
assessment. San Diego, CA: Singular Publishing, 1992:159181.
22. Cornelisse LE, Seewald RC, Jamieson DG. Wide dynamic-range compression hearing aids: the
DSL[i/o] approach. Hear J 1994;47:2326.
23. Gelfand SA, Silman S. Apparent auditory deprivation in children: implications of monaural versus
binaural amplification. J Am Acad Audiol 1993;4:313318.
24. Johnson CD, Rees KA. Amplification options for infants and toddlers. Semin Hear 1995;16:140
150.
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central auditory processing. Rockville, MD: ASHA, 1992.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

92 PEDIATRIC FACIAL FRACTURES
Head & Neck SurgeryOtolaryngology
92




PEDIATRIC FACIAL FRACTURES
PETER J. KOLTAI

P.J. Koltai: Section of Pediatric Otolaryngology, Cleveland Clinic Foundation, Cleveland, Ohio.


Epidemiology
Emergency Management
Radiographic Examination
Etiology
Facial Growth and Trauma
Rigid Fixation
Surgical Approaches
Nasal Fractures
Fractures of the Mandible
Fractures of the Condyle
Fractures of the Arch of the Mandible
Dentoalveolar Fractures
Fractures of the Midface
Fractures of the Zygomaticomalar Complex
Fractures of the Nasoethmoidal Complex
Fracture of the Orbital Roof, Supraorbital Rim, and Frontal Bone
Fractures of the Floor of the Orbit
Fractures of the Maxilla
Conclusion
Acknowledgment
Chapter References
The last 20 years have seen a revolution in the management of facial fractures with the
use of internal rigid fixation by means of craniofacial exposure. Refinements in
biocompatible materials of great delicacy and strength, such as titanium plates and
screws, along with advances in understanding biomechanics of the face, have rendered
complex injuries consistently amenable to accurate three-dimensional reconstruction.
With the availability of educational courses that train surgeons in the techniques of
internal rigid fixation, these advanced techniques have become routinely used in the care
of adult patients. The suitability of rigid internal fixation to treat children remains
controversial. There are many concerns about the effect of im-planted plates and screws
in the face of a growing child. Some evidence suggests that elevation of the functional
matrix off the underlying facial architecture to gain exposure to the fractures may alter
development.
The fundamental concepts of facial traumatology are the same for children and adults.
The goal is to restore the underlying bony architecture to its preinjured position in a
stable manner with minimum aesthetic and functional impairment. For children, the
management of complex facial injuries is best accomplished with techniques that may
adversely affect craniofacial development. Although it is not entirely possible to solve
this problem, an extensive body of experimental and clinical information exists on the
appropriate management of pediatric facial fractures. This knowledge can be used to
formulate a rational treatment plan in most cases.
EPIDEMIOLOGY
Trauma is the leading cause of death among children in the United States. It accounts for
half of all deaths in this age group. Nearly 15,000 children die of trauma each year, and
approximately 100,000 are permanently disabled. More than $15 billion is spent each
year treating children for injuries (1). Despite this epidemic of trauma, serious facial
fractures among children are relatively rare. The incidence of pediatric facial fractures
has been reported to be as low as 1.5% and as high as 15% (2,3,4,5 and 6). It is generally
accepted that children younger than 5 years are least likely to sustain serious facial
injuries. At my institution, fractures in the pediatric age group accounted for 9% of all
maxillofacial injuries over a 5-year period (2). The incidence was distributed evenly
across all pediatric age groups, an observation at variance with other reports. Adolescents
had adult facial-fracture patterns and were more likely to have severe injuries that
necessitated surgical intervention. Some studies suggest a male preponderance (3);
however, my colleagues and I found a consistent pattern across sexes. This pattern
probably reflected the high incidence of motor-vehicle-passenger accidents among our
patients, a mechanism of injury that tends to affect the sexes equally (4).
Nasal fractures are by far the most common facial fractures among children. Most of
these children are treated in the office setting, so the true incidence in relation to more
serious injuries is difficult to ascertain. Fractures of the mandible are less common but
account for most injuries that necessitate hospitalization and thus are reported more
routinely in the literature. Depending on whether nasal fractures are included, mandibular
fractures constitute 20% to 50% of reported pediatric facial fractures. The condyle is the
most vulnerable part of a child's mandible, accounting for 40% to 70% of mandibular
fractures. Adolescents have a high incidence of fractures of the arch and body of the
mandible, reflecting the adult pattern. Dentoalveolar fractures often are managed in the
outpatient setting, and the frequency is difficult to define precisely.
After nasal fractures, orbital fractures are the most common midfacial fractures; they
occur among 20% to 25% of all patients. Fractures of the zygomaticomalar complex
occur among 10% to 20% of patients. Complex midfacial fractures occur among 5% to
10% of patients. Frontoorbital and panfacial fractures, especially in the preadolescent
years, are rare and sporadic.
Neurocranial and orthopedic injuries frequently are associated with severe facial fractures
in the pediatric age group. In our series, 30% of children with facial fractures sustained
associated injuries. The frequency of intracerebral trauma and skull fractures is reported
to be as high as 60%, especially among younger children (2,4). The high frequency of
associated injuries reinforces the importance of complete initial assessment of a child
with facial trauma and may complicate management considerably if the rapid healing of
bony injuries begins before the child's condition is neurologically stable for facial
reconstruction.
EMERGENCY MANAGEMENT
The initial assessment of a child with facial fractures should follow the basic principles of
trauma management. Attention is immediately paid to the airway, breathing, and
circulationthe ABCs. The airway can be managed in a variety of ways, depending on
the type of injury. With isolated maxillofacial injuries, appropriate positioning of the
child usually is sufficient. Gentle suctioning of the mouth and pharynx to remove saliva,
blood, and even loose teeth and bone fragments may be necessary. A midline traction
suture in the tongue can prevent retrodisplacement in extreme cases of mandibular
fracture.
Orotracheal intubation is needed when positioning is inadequate to maintain the airway.
This often occurs with more complex facial fractures accompanied by profuse bleeding or
when there is neurocranial injury with impairment of the respiratory drive. Orotracheal
intubation is performed with the assumption that cervical spinal injury has occurred, and
thus manipulation of the neck is avoided until cervical radiographs have ruled out a high
spinal injury. My colleagues and I prefer to avoid cricothyrotomy or crash tracheotomy in
the emergency department if orotracheal intubation is at all possible. The need for
tracheotomy in the care of pediatric patients with severe facial fractures is controversial.
Many surgeons view avoidance of tracheotomy as a sign of skill. Experience at my
institution suggests that when there are severe panfacial fractures or when major facial
fractures are associated with intracranial or visceral injuries, tracheotomy is a safe and a
comfortable way of caring for a child. Hypovolemic shock can be caused by blood loss
associated with severe fractures. We have seen several instances in which hemorrhage
into the airway severely compromised respiration. Intubation protects the airway, and
volume expansion can be achieved with intravenous crystalloid solution. Transfusion
with type-specific red blood cells rarely is necessary.
An orderly examination of the head and neck is performed after the primary survey has
been completed and the ABCs have been managed. A complete neurologic evaluation,
examination of the neck and cervical spine, and inspection of the eyes, nose, and oral
cavity are performed. Ophthalmologic assessment is mandatory in the care of children
with midfacial trauma to rule out vision loss and intraocular abnormalities, to evaluate
ocular motility, and to check pupillary reflexes. Injury to the anterior wall of the ear canal
can be associated with fractures of the condyle and is detected by means of otoscopic
examination. Anterior rhinoscopy discloses injuries to the nasal septum, including septal
hematoma and even the possibility of cerebrospinal rhinorrhea.
Global assessment of the face is made by means of inspection and palpation. Facial
asymmetry, edema, ecchymosis, periorbital swelling, trismus, and malocclusion are
highly suggestive of facial fractures. Bimanual examination highlights asymmetry and
reveals areas of tenderness and crepitation. Mobility of the midface can be assessed by
means of grasping the upper incisors and rocking the premaxilla while the head is being
held steady with the opposite hand. Intraoral palpation for irregularities and visualization
for ecchymosis in the upper gingivolabial sulcus suggest fracture of the anterior and
lateral maxillary buttresses. The examiner can place his or her fingers in the external
auditory canal to assess the temporomandibular joints. Intraoral and extraoral digital
examination generally reveals fractures of the mandibular arch.
RADIOGRAPHIC EXAMINATION
As with adults, computed tomography (CT) has revolutionized the imaging of facial
fractures in children. Axial CT scans are useful in evaluating fractures of the orbital walls
and maxilla but do not consistently reveal fractures of the orbital floor and roof and the
palate. Direct coronal projections provide additional information for these sites but can be
difficult to obtain if the child is uncooperative or injured. The compromise under these
circumstances is to have a neuroradiologist render reformatted coronal CT scans to define
the anatomic features of interest. Reformatting also can render three-dimensional CT
reconstructions that are a useful adjunct to two-dimensional CT scans for planning the
surgical management of facial fractures.
The most useful study for imaging the pediatric mandible is the panoramic view, which
shows the entire jaw. This study, however, requires a cooperative patient, and that is not
always feasible. An axial CT scan often is a helpful compromise, especially if it can be
reformatted into coronal and three-dimensional images. Alternative views, such as the
Towne view, the lateral oblique projection, and intraoral projections, usually can be
obtained without difficulty.
Radiographic evaluation of nasal fractures generally is of little use. Nevertheless, these
studies almost universally are obtained in the emergency department when such an injury
is suspected. Given the medicolegal environment, it is unlikely that such a practice will
change. An important point to remember is that serious nasal fractures with dorsal
flattening necessitate appropriate imaging with CT to rule out an occult injury to the
nasoethmoidal complex .
ETIOLOGY
The developmentally specific anatomy of a child's face and the types of force that
produce injury are the main factors that determine the cause of pediatric facial fractures.
The first 6 years of a child's life are protectedthere is low risk of serious injuries. When
all forms of fractures are considered, childhood play is the most frequent cause of facial
fractures, but because it produces falls from low heights, play rarely causes serious
injury. Infants have special vulnerability, such as birth injuries and child abuse. Bicycle
accidents can be a threat to older children and adolescents. Motor vehicle accidents are
the most common cause of serious facial fractures among children (2,3,4,5,6 and 7).
Analysis of facial development between infancy and adolescence is important for
understanding the difference between pediatric and adult facial fractures. An infant is
born with a large cranium relative to the face; the craniofacial ratio is 8:1. The bones of
the face are not fully mineralized, the sutures are not fused, the cortices are thin, and
there is a greater proportion of cancellous bone, which envelopes the tooth buds. Of the
paranasal sinuses, only the maxillary and ethmoidal sinuses are present as tiny mucosal
recesses that occupy a fraction of the facial volume of an adult. Thus the infant's
craniofacial complex is an elastic but solid structure. With growth and development, it
matures into the brittle, hollowed-out face of the adult, with its robust structural
buttresses that provide the framework for the multiple functions of the adult face.
Approximately 80% of cranial growth occurs during the first 2 years of life. Although
facial growth also is rapid during this period, it is only after the age of 2 years that the
face begins to grow faster than the skull. By 7 years of age, the orbit and brain are near
completion of growth, and the interorbital width is close to the adult measurement. At
approximately the same stage of development, the face begins to project forward and
downward, unfolding from beneath the overhanging cranium. This phenomenon is the
result of both growth and vertical and horizontal pneumatic expansion of the maxillary
and ethmoid sinuses. Concurrent is loss of the deciduous teeth and the eruption of the
secondary dentition.
FACIAL GROWTH AND TRAUMA
Alteration of facial growth as a consequence of pediatric facial trauma is well recognized
but is not inevitable. Development of the face is a combined process of growth and
remodeling with maturational changes that differentiate the unique features of a child's
face from those of an adult. Alterations of growth and remodeling due to trauma cause
the deformities seen in adulthood.
Growth studies of mandibular and midfacial fractures are scarce. It has long been known
that the condyle is an important site of mandibular growth and that injuries to this area,
the most common area to be fractured in the pediatric age group, can but do not
consistently cause facial asymmetry. MacLennan reviewed 180 cases of condylar
fractures, five among children younger than 10 years. He found that although most
injuries heal without functional impairment, crush injuries to the condylar head before the
age of 5 years predispose a child to ankylosis and growth disturbances. Lindahl and
Hollander compared the process of remodeling of the condyle after fracture among
children and adults. They found that between 3 and 11 years of age, extensive remodeling
of the condylar fractures generally results in normal anatomic features (Fig. 92.1A).
Lesser remodeling was found among adolescents, and minimal remodeling was found
among adults. In a study of 55 children with fractures of the condyle, Norholt et al. found
that younger children have fewer long-term problems due to injuries than do older
children, suggesting that growth compensates for the injury. Rowe, however, found that
injuries sustained before 3 years of age generally produced severe deformities, those that
occurred after 6 years caused moderate deformities, and those sustained during
adolescence produced only mild deformities.

FIGURE 92.1. A: Tomogram of a right subcondylar
fracture in a 5-year-old boy shows comminution of the
condylar neck. B: Appearance 6 months later after A. The
only treatment was a soft diet and a brief period of
analgesic therapy. Reconstitution and anatomic
remodeling of the condyle are evident.



McGuirt and Salisbury (8) conducted a study with 28 patients with childhood mandibular
fractures and found obvious dentofacial abnormalities among 13 of the patients and
cephalometric abnormalities among 18 of the patients. The most severe abnormalities
were associated with condylar injuries (Fig. 92.2A, Fig. 92.2B). Authors vary in their
interpretations of these observations of alteration of facial growth. The theories include
loss of the stimulus to normal growth, mechanical restriction produced by scarring and
loss of motion, altered muscular activity on the injured side, and interruption of vascular
supply to the teeth. None of the reports suggests a correlation between the type of
technique of management of the mandibular fractures in children and the long-term
outcome with regard to alteration of facial growth. The principle that can be harvested
from the review of this research, most of which was done well over a decade ago, is that
prolonged follow-up evaluation of children with mandibular fractures is mandatory and
that orthodontia may be an important adjunct in long-term management.

FIGURE 92.2. A: Three-dimensional computed
tomographic (CT) reconstruction of a 3-year-old child
with mandibular hypoplasia, retrognathism, and right
temporomandibular ankylosis. The child had a history of
crush injury to the right mandibular condyle in the first
year of life. B: Three-dimensional CT scan of the child
depicted in A shows a normal left condyle and an
abnormal, hyperplastic right condyle with a foreshortened
condylar neck ankylosed in the right temporomandibular joint.



Rigid Fixation
Whereas the use of rigid plate fixation to treat adults has widespread acceptance, use of
fixation to treat children remains controversial because of concern about impairment of
facial growth. The unresolved question is whether transient stabilization of the facial
skeleton causes permanent growth retardation. This issue has been addressed in several
animal studies. Lin et al. (9) performed frontoorbital craniotomy on four groups of
kittens. In the first group, fixation was by wire osteosynthesis. In the second group,
fixation was with minicompression plates. The third group of kittens was subjected to
plate fixation without osteotomy. The fourth group was subjected to incision and
periosteal elevation alone. Three-dimensional CT and cephalometrics were used for
growth analysis and showed significant growth restriction in the groups subjected to
osteotomy. Growth retardation occurred among the groups treated with wires and plates,
but no difference was found in the degree of restriction. Marshall et al. (10) performed
miniplate fixation along the coronal suture and nasofrontal suture on two groups of
beagle puppies. The investigators found a discernible but insignificant skeletal
asymmetry 10 months after surgery.
It is difficult to draw firm conclusions from these animal studies about the use of plate
and screw fixation after trauma to young children except that it should be performed with
caution and reserved for fractures in which the original features are difficult to restore by
other means. Most of the studies were conducted with very young animals, which have
much more rapid facial development than do humans. The use of rigid fixation to treat
human infants, who are in the most rapid phase of craniofacial growth, usually is reserved
for repair of congenital craniofacial anomalies, not for trauma. The use of cranial plates
to treat infants occasionally results in intracranial translocation of the plates (11,12). This
observation has undermined the conceptual safety of metal implants in young children
and suggests that plate removal should be considered. Indeed, using plates on rapidly
growing bone is like using wire to support the trunk of a growing tree. Although the wire
remains stationary, the tissues of the tree grow around the wire, incorporating it into the
fabric of the tree. Another analogy is that as a glacier flows around the rocks in its path,
the rapidly growing cranial bone of an infant flows around the implanted metal plates
during the process of growth, surrounding it and incorporating it within the framework of
the bone. Because most children who have severe facial fractures that necessitate rigid
fixation are older than 6 years (before which age 80% of craniofacial growth occurs), the
process of translocation has not been observed.
A fundamental component of internal rigid fixation is the use of bone grafts to bridge
defects caused by traumatic avulsion of bone fragments (13). This is applicable to
children, because bone grafts can be incorporated into the growing face and act as a
substrate for further growth. Rib grafts have long been used for mandibular
reconstruction in the care of children with hemifacial microsomia. The pliability also is
advantageous around the orbital rim. Cranial bone grafts are the workhorse in pediatric
craniofacial surgery. They are also the most useful replacement for traumatic bone loss in
the midface region of children. After adolescence, cranial bone grafts can be harvested in
one stage. For children younger than 10 years, however, it is best that a neurosurgeon
harvest a full-thickness skull plate, which can be split on the back operating table. The
inner bone table is used for grafting, and the outer table is replaced into the skull with
plates and screws (Fig. 92.3).

FIGURE 92.3. Full-thickness calvarial bone being split
for use as a bone graft to the orbit in a 6-year-old child.



Management of complex facial fractures requires understanding both the risks and the
benefits of rigid fixation. Minimally displaced fractures often are best left alone or
managed with closed reduction. Moderately displaced fractures require more judgment
about the degree of exposure and fixation needed; however, stability after reduction is the
best guide to the magnitude of intervention. There is no alternative to rigid fixation in
certain complex cases. The optimal hardware available to most maxillofacial surgeons is
small, finely machined titanium plates and screws, the utility of which is well recognized.
It is difficult to avoid using these materials. Failing to perform adequate reconstruction is
unacceptable because the soft tissues shrink and contract to mirror the abnormal skeletal
infrastructure. Interfragmentary wiring of difficult fractures results in unstable
reconstruction and yet has the potential for growth retardation. Bone loss of the buttresses
of greater than 5 mm should be bridged rigidly with calvarial bone grafts. Plates should
be as small as possible without compromising stability. They also should be used in short
segments. Crossing more than one suture line should be avoided. Questions about
potential growth restriction from implants and consideration for removal are valid but
must be weighed against the additional injury to facial soft tissues required by removal.
Development with resorbable implants should make the issue of removal irrelevant.
Surgical Approaches
Most pediatric facial fractures, such as nasal fractures or fractures of the zygomatic arch
can be managed with traditional closed techniques or with limited open techniques.
Nevertheless, for severe injuries that necessitate extensive rigid fixation, the development
of hidden extended incisions for complete exposure is extremely useful. The entire facial
skeleton can be accessed and reconstructed with one or more of five incisions (14). The
arch of the mandible can be exposed through a lower gingivolabial sulcus incision,
although comminuted mandible, angle, and ramus fractures probably are best exposed
through the external approach. The upper third of the face, including the zygomatic
arches, upper orbital rims, and nasoethmoidal region, can be exposed through a coronal
incision. The inferior orbital rim and orbital floor can be exposed with a subciliary or
transconjunctival incision. The maxilla, particularly the important anterior buttresses and
lateral buttresses, can be exposed by an upper gingivolabial sulcus incision. Appropriate
closure is an important finishing touch to craniofacial exposures, especially in the
treatment of children, in whom the functional matrix must be precisely fitted back onto
the bone from which it was stripped. Chapter 64, Chapter 65, Chapter 66, Chapter 67,
Chapter 68 and Chapter 69 describe the clinical details of these exposures, which do not
differ from those used to treat adults.
Nasal Fractures
The nose of a child is markedly different from that of an adult. The main difference is
that the projecting tissue in a child's nose is soft, compliant cartilage that readily bends
during a blow to the face. The force is dissipated across the maxillary soft tissues and
lateral buttresses. The result is a broad area of edema with loss of anatomic specificity.
The soft projecting cartilages rarely sustain permanent injury, whereas the septum, which
is more rigid and surrounded by bone in a tight perichondrial covering, is more likely to
be fractured. Several types of septal injuries are known to occur. The septal
perichondrium can be torn away from the cartilage, leaving a potential space into which
bleeding can occur; the result is septal hematoma. The septum can be torn from its
inferior and posterior bony attachment. The result is immediate nasal obstruction and
long-term hypertrophic growth disturbances. Injury to the caudal septum can cause
immediate nasal obstruction and long-term twisting deformities.
The nasal bones have little projection in infants and very young children and are not
frequently broken. Children older than 6 years are more susceptible to bony fractures.
When the fractures do occur, they often are of the greenstick variety. Midline injuries can
result in open-book fractures with a central depression and lateral flaring of the nasal
bones. Occult nasal orbitoethmoidal fracture always should be suspected with fractures of
the nose.
There are two stages in the care of children with nasal fracturesinitial evaluation and
definitive management. The immediate examination of a child with a nasal fracture has
limited value because of the inevitable swelling across the midface. It is often difficult to
differentiate a soft-tissue swelling with no fracture and a modestly displaced fracture. In
most cases, a few days must elapse for the swelling to diminish before the true extent of
the deformity can be appreciated. Nevertheless, immediate intranasal examination is
important to rule out the presence of septal hematoma. Although many children have
difficulty breathing through the nose after an injury and many have had epistaxis, only
septal hematoma manifests as a purple bulge confined to one side of the nose. The bulge
can be compressed with a cotton-tipped applicator but does not shrink with topical
vasoconstriction. Uncontrolled hematoma can produce an obstructive, thick fibrotic
septum or loss of the quadrilateral cartilage and saddle-nose deformity. Thus hematoma
must be recognized and managed.
Treatment is surgical and is best performed with general anesthesia. Once the child is
anesthetized, the hematoma is evacuated through a hemitransfixation incision, and the
rest of the septum is explored for other injuries. The transfixion incision is closed with 5-
0 chromic catgut, and the septal leaflets are reapproximated to the cartilage with through-
and-through mattress 4-0 chromic catgut and mini-Keith needle. I try to avoid using
polymeric silicone splints, but sometimes splints are necessary to support fractures of the
septum. The nose is packed with antibiotic impregnated rolls of perforated film absorbent
dressing or gauze for 2 or 3 days after the operation. The child receives broad-spectrum
antibiotics.
If anesthesia is given for repair of the septum, the rest of the nose is repaired at the same
time; however, when the septum does not need immediate attention, the child is asked to
return in 3 or 4 days, when a more accurate assessment is possible. Definitive
management is undertaken if bony or septal injuries are found that are likely to cause
functional or a cosmetic deformity. In most cases, the fracture is best managed by means
of closed reduction with intranasal instrumentation and bimanual external manipulation.
When children are not seen until 2 to 3 weeks after the injury, open reduction is
necessary. Open reduction also can be helpful in the management of greenstick fractures,
which are not readily relocated to the normal anatomic positions without completion
osteotomy. This procedure can be performed with a 2-mm osteotome. Most fractures tend
to stay in place after closed reduction alone; however, the presence of unstable fragments
necessitates intranasal packing for several days. The fracture is supported externally with
a thermoplastic cast applied over sterile adhesive strips.
The septum usually is difficult to reconstruct with closed techniques; periosteal elevation
through a hemitransfixation incision can be used. Emphasis is on realignment of the
fragments rather than resection. Mattress sutures and intranasal packing can be used to
support the reconstruction for several days after the operation.
Fractures of the Mandible
The management of mandibular fractures for children differs from that for adults because
of concern for the growth of the mandible and developing dentition. Nevertheless, the
goals of accurate alignment with restoration of the occlusion and reduction of fragments
are the same. Among infants younger than 2 years, eruption of the deciduous teeth is
incomplete, and it is difficult to achieve adequate immobilization with the most familiar
techniques. Accurate alignment in the management of fractures of the body and arch can
be obtained with an acrylic splint, which is fabricated with the help of a dentist.
Fabrication requires taking a cast of the upper and lower dental arches. A plaster cast is
made of the impression, and the lower cast is cut and realigned with the cast of the
maxillary dentition to reestablish the occlusion in plaster. The acrylic splint is fabricated
on the mandibular plaster cast and wired in place with circummandibular wires. It is
important to thin the posterior portion of the splint over the posterior teeth to prevent
premature posterior closure, which results in an open bite. The acrylic splint is left in
place for 2 to 3 weeks and is removed in the operating room with the patient under
general anesthesia. Intermaxillary fixation is not necessary (Fig. 92.4).

FIGURE 92.4. A: Towne view shows right
parasymphyseal mandibular fracture in a 3-year-old girl.
B: Clinical photograph shows the fracture depicted in A.
C: Acrylic splint fabricated on a plastic cast of the
mandible. The original impression of the mandibular arch
was cut and the occlusion established to the maxillary
impression before fabrication of the splint. D: Acrylic
splint wired into place with circummandibular wires.



Between 2 and 5 years of age, the primary teeth have firm roots that can be used for cap
splints and arch bars. Arch bars, however, can be technically difficult to maintain during
this period if they are not adequately secured below the gum line on a child. During this
time, additional support with pyriform aperture suspension and circummandibular wiring
is probably advisable although not always necessary. Between 6 and 12 years of age,
resorption of the deciduous roots occurs, and during this time, arch bars can be
successfully applied; however, additional support is needed with pyriform aperture
suspension and circummandibular wiring because of the foreshortened tooth roots. Many
children in this age group have orthodontic appliances in place. The appliance can be
used successfully for brief periods of intermaxillary fixation without harm to the
appliances themselves. Adolescents have an adequate complement of permanent teeth
that provide safe anchors for fixation. For them, standard intermaxillary fixation with
arch bars is useful. My colleagues and I have used a fixation technique that depends on
vertical placement of miniplates secured with two monocortical screws to the mandible
along its lower border medial to the inferior alveolar nerve. A symmetrically placed pair
of vertically oriented miniplates is suspended on either side of the pyriform aperture with
two monocortical screws. The vertically oriented plates are connected with wire to bring
the teeth into alignment.
Fractures of the Condyle
Condylar fractures are classified into three anatomic typesintracapsular crush fracture
of the condylar head, high condylar fracture through the neck above the sigmoid notch,
and low subcondylar fracture. The third type is the most common and is often an
incomplete greenstick injury. Clinical and experimental observations support a
conservative closed approach to the management of most fractures of the condyle in the
pediatric age group. Although some experts advocate open surgical treatment, the
primary decision in the care of many children is not whether to open the fracture but
whether the child needs immobilization with intermaxillary fixation.
Children with unilateral condylar fractures often have normal range of motion and normal
occlusion. For such injuries, only a soft diet and movement exercises are necessary. If the
movement deviates from the midline despite normal occlusion, placement of arch bars for
use with guiding elastic bands is considered. This method of treatment also is appropriate
for bilateral subcondylar fractures when occlusion and function are normal (Fig. 92.5). It
is not uncommon to see an open bite deformity in some unilateral and in most bilateral
subcondylar fractures. This deformity causes retrusion of the mandible and limitation of
movement. Under these circumstances 2 to 3 weeks of immobilization followed by 6 to 8
weeks of wearing guiding elastics produces normal function.

FIGURE 92.5. Coronal (A) and three-dimensional
reconstruction (B) computed tomographic images of a 10-
month-old infant with bilateral displaced subcondylar
fractures. Coronal view shows symphyseal greenstick
fracture of the lingual cortex. This child was treated
expectantly.



Fractures of the Arch of the Mandible
Management of fractures of the mandibular arch among children can range from
observation to open reduction with rigid fixation. Anterior fractures of the arch with
minimal to moderate displacement often can be reduced with careful manual
manipulation with the patient under general anesthesia. Immobilization is achieved with
interdental wiring, arch bars, or cap splints. Use of acrylic splints can be considered in the
treatment of children younger than 7 years.
When bone-to-bone reapproximation is needed because of unfavorable alignment of
fractures, open reduction may be necessary, even for very young children.
Reapproximation can be accomplished with interfragmentary wiring or with
monocortical miniplate fixation in conjunction with intermaxillary fixation. Both
techniques require great care in drill-hole placement to prevent iatrogenic injury to the
developing tooth buds (Fig. 92.6). In the treatment of children with permanent dentition,
the principle of bicortical rigid fixation is applicable.

FIGURE 92.6. Proximity of the unerupted canine and
bicuspid teeth to the lower margin of the mandible.



Fractures of the body and angle of the mandibles of children often are incomplete
monocortical cracks with normal occlusion and movement. These greenstick fractures are
best managed with a soft diet and symptomatic therapy. Displaced fractures necessitate
more aggressive management, depending on the direction of the muscle pull on the
fragments, the degree of distraction, and the availability of dentition. Intermaxillary
fixation is adequate in most cases; however, if distraction of the lower border cannot be
controlled conservatively, open reduction with internal fixation by means of
interfragmentary wiring or monocortical miniplating is necessary. The posterior portions
of the mandible traditionally need external incisions for adequate access and
visualization. Transcutaneous sleeves and better bone- and plate-holding instrumentation
simplify intraoral reduction.
Dentoalveolar Fractures
Dentoalveolar fractures among children with primary teeth are not the serious dental
emergency they are among adolescents and adults. When a secondary tooth is avulsed,
survival depends on early reimplantation, generally within an hour of injury. It can be
difficult to determine whether a child's tooth is primary or secondary, especially during
the period of mixed dentition; thus implantation usually is attempted.
The incisors and canines are the most commonly injured teeth because they are
prominent. Fractures can involve the crown, the deep pulp, or even the surrounding
cortex. Acute treatment entails cleaning the avulsed tooth in saline solution and replacing
it in the socket. If the child is not cooperative, the tooth can be kept in saline solution,
soaked in gauze, or immersed in a bowl of milk until dental reimplantation and
stabilization. Reduction of multiple teeth with avulsed alveolar bone is a difficult injury
to stabilize and revive.
Fractures of the Midface
The orbit and the nasoethmoidal region are the aesthetic focus of the face, and injuries to
this region can leave children with serious deformities. The severity and direction of the
impact determine the extent of these injuries, which can range from simple blowout
fractures of the orbit to highly comminuted injuries with complete disruption of the bony
and soft-tissue components of the central core of the face. The severity of the injury
dictates the management, which varies from simple observation to extensive craniofacial
reconstruction with bone grafting and rigid fixation. Physical examination and CT are
used for accurate diagnosis of both functional and the structural changes. Ophthalmologic
evaluation is mandatory for visual acuity. Despite the presence of periorbital edema,
ecchymosis, and subconjunctival edema, which often obscures its position, the globe
nevertheless must be inspected for exophthalmos, enophthalmos, vertical dystopia,
rupture, and intraocular pressure. Motility is assessed by means of force duction testing
while the child is under anesthesia. The integrity of the infraorbital and supraorbital
nerves must be assessed, and intercanthal distance is measured for traumatic
hypertelorism. The integrity of the medial canthal ligaments is best assessed with
bimanual examination while the child is anesthetized.
Fractures of the Zygomaticomalar Complex
Paralleling pneumatization of the maxillary sinus, fractures of the zygomaticomalar
complex usually do not occur before a child is 5 years of age. Before this age, more
fractures of the malar bone and mandibular arch occur. After this age, the geometric
pattern of fractures resembles that among adults. My colleagues and I, however, have not
seen the severe comminution that occurs with high-energy fractures among adults.
Surgical correction of fractures of the zygomaticomalar complex is indicated when there
is bony displacement. This necessitates adequate exposure of the fractured buttresses, a
process called triangulation, because it involves control of the three main buttresses.
In most fractures of the zygomaticomalar complex among children, medial displacement
of the malar fragment occurs with only greenstick fractures of the frontozygomatic suture
and zygomatic arch. For these injuries single-point fixation of the zygomaticomalar
buttress usually is adequate. In more involved injuries, two-point and even three-point
fixation may be necessary. Isolated fractures of the zygomatic arch can be repositioned
with a Gilley approach. Prolapse of orbital contents into the maxillary sinus often can be
supported with absorbable gelatin film; however, in more complex and severe injuries,
my colleagues and I have used calvarial bone grafts. The use of synthetic implants to treat
children is controversial and generally is avoided.
Fractures of the Nasoethmoidal Complex
Fractures of the nasoethmoidal complex can vary from minimal dislocation to highly
comminuted compound fractures that extend into the surrounding frontal bone, orbits,
and maxilla. The extent of comminution and the depth of comminution of the central core
of the face determine the severity of the fracture and the difficulty of reconstruction.
Computed tomography is invaluable for preoperative planning of nasoethmoidal
fractures. Axial views define the degree of retrodisplacement of the central fragment into
the ethmoidal sinus, and the coronal view defines displacement of the medial wall and the
floor of the orbit (Fig. 92.7). Medial canthal integrity is mandatory and is assessed with a
hemostat inserted into the nose toward the medial orbital rim. The child should be
anesthetized for this examination. Mobility of the underlying fragments suggests that the
bone with its canthal attachment has been displaced and that reconstruction of the nasal
maxillary buttress and possibly transnasal wiring is necessary.

FIGURE 92.7. Coronal computed tomographic
reconstruction of a complex nasoethmoidal fracture in a
12-year-old child. Disruptions of the nasomaxillary
buttress are evident on the right, the medially orbital
walls bilaterally, and the orbital floor on the left.



Measurement of soft-tissue intercanthal distance is difficult because no data exist about
these distances among traumatized children. Moreover, ethnic, racial, and sex variations
exist. Nevertheless, the average intercanthal distance at 4 years of age is approximately
25 mm; by age 12 years, 28 mm; and by adulthood, 30 mm. It is obvious from these
numbers that a near-adult intercanthal distance is achieved at a very early age; hence an
easy mistake in the treatment of children is to set the intercanthal distance too wide.
Intercanthal distances 5 mm more than the average values tend to be indicative of and 10
mm confirms the diagnosis of displaced fractures of the nasoethmoidal complex.
Undercorrection is common, and an attempt is made to excessively narrow the distance
between the eyes and excessively project the nose of a child. The use of nasal dorsal bone
grafts to manage midfacial crush injuries is as important for children as it is for adults and
is not left for later correction.
Fracture of the Orbital Roof, Supraorbital Rim, and Frontal Bone
Fractures of the orbital roof among young children are probably far more common than
traditionally has been recognized. This is attributable to the availability of direct coronal
CT evaluation in conjunction with an increased awareness of the clinical presentations of
these injuries. There usually is a history of a blow to the brow, often associated with a
late-developing periorbital hematoma. The delay in swelling can be an important clue in
differentiating fractures of the roof from other orbital injuries. Proptosis or dystopia can
occur but may not be immediately apparent. Ophthalmologic evaluation, as in all orbital
trauma, is mandatory; however, the orbital soft tissues and the globe rarely sustain long-
term damage.
Messinger et al. suggested a classification system for orbital roof fractures based on the
pattern of injuries on CT scans. Type I fractures have comminution of the orbital roof but
no displacement. Type II fractures have displacement of the fragments toward the
anterior cranial fossa. Type III fractures have displacement inferiorly into the orbit. Most
children need surgical repair of the roof or the superior orbital rim. Nevertheless, type III
blow-in fractures, which are known to cause permanent exophthalmos, vertical dystopia,
and traumatic encephalocele, can be considered for reconstruction if the ocular morbidity
appears fixed or if it has not begun to resolve within 7 to 10 days of the injury. Posnick
(12) suggested that severe fractures of the orbital roof often are associated with fractures
of the forehead combined with brain injury and dural tears with cerebral spinal fluid
leakage. This is a frequent pattern of injury among infants and children younger than 5
years when severe anterior craniofacial injuries occur. The timing of management of
these complex fractures must take into account concurrent intracranial injury.
Neurosurgical intervention takes priority; however, concurrent reconstruction often is the
best way to achieve rapid facial rehabilitation for the injured child.
Fractures of the Floor of the Orbit
Fractures of the orbital floor among children, like fractures of the zygomaticomalar
complex, parallel the pneumatization of the maxillary sinus. It is unusual to see these
injuries among children younger than 5 years. These injuries are the most common
isolated type of fractures of the orbit among children older than 7 years. Isolated fractures
of the floor share clinical findings with more extensive injuries.
Coronal CT is best for depicting defects of the orbital floor. Ophthalmologic evaluation is
mandatory. There is little disagreement about the need for exploration of fractures of the
orbital floor in conjunction with concurrent maxillary injuries. Nevertheless, the
management of isolated blowout fractures has been unnecessarily controversial. Most
children who have isolated blowout fractures are observed for 7 to 10 days. If at that
point they continue to have enophthalmos, diplopia, or pain with motion, exploration is
undertaken. Large fractures are explored routinely as are fractures that on CT have
obvious muscle entrapment. Absorbable gelatin film usually is sufficient for
reconstructing small defects of the floor; however, large disruptions are best repaired
with calvarial bone grafts.
Fractures of the Maxilla
As among adults, maxillary fractures among children are classified with the LeFort
system. This anatomic classification is inadequate to describe the severity of the injury
and the complexity of the reconstruction needed. A functional classification system has
been useful for predicting the difficulty of reconstruction. Type I fractures are minimally
displaced and generally are not comminuted. With these types of injuries, the main
buttresses are cracked, but the fragments are still close to the original anatomic location.
Type II fractures are moderately displaced with some area of comminution. With these
injuries, there can be multiple fractures of the buttresses; however, the fragments are
recognizable and are large enough to accept plate and screw fixation readily. Type III
fractures are severely displaced with multiple comminution of the main supported
buttresses resulting in a highly unstable fracture that necessitates three-dimensional
stabilization and the use of bone grafts for reconstruction of the shattered buttresses. This
classification is applicable to most areas of the facial skeleton. My colleagues and I have
found a statistically significant correlation between type II and type III fractures and the
need for rigid fixation in the care of children (Koltai PJ, et al., unpublished data, 2000).
Maxillary fractures are uncommon among children. Associated neurocranial injuries are
frequent because the force needed to cause maxillary fractures often is great enough to be
transmitted into the cranial cavity. Coordination of care with a pediatric intensive care
specialist, ophthalmologist, neurologist, neurosurgeon, and anesthesiologist is needed.
Although immediate operative intervention is ideal, there often are medical
contraindications. Nevertheless, marked fracture displacement must be reduced within 10
days because rapid interfragmentary healing makes late correction technically difficult.
CONCLUSION
Children of all ages can sustain serious maxillofacial injuries and can have unique
patterns of fractures depending on age. Before the age of 5 years, when the craniofacial
complex is more elastic but more solid, fractures tend to be shearing and greenstick in
nature. Even large forces displace blocklike segments rather than cause severe
comminution. Between the ages of 6 and 12 years, children have intermediate patterns of
fracture, but if the forces are great enough, comminution can occur. Adolescents display
an adult pattern of facial fractures. The growth and mobility of the mandible facilitate
repair of fractures because most injuries heal and can be managed conservatively with
either observation or intermaxillary fixation. Midfacial injuries, on the other hand, are
more likely to cause problems with facial growth and development and to result in
permanent deformities if left uncorrected. The goal of therapy is to achieve a balance
between the stability of the fracture and the intensity of intervention. Stability and correct
anatomic reduction take precedence over the effect on the alteration of facial growth as a
consequence of periosteal elevation needed for the reconstruction. Metal plates and
screws can be used safely in the face of a child to achieve stability but are reserved for
injuries that cannot be equally well reduced with less invasive techniques. Plates must not
cross more than one suture line and must be the smallest possible size that maintains
reduction. Consideration of removal is appropriate but is weighed against additional soft-
tissue injury. Calvarial bone grafts are used as a substrate for future growth when there is
traumatic bone loss.
ACKNOWLEDGMENT
Sincere appreciation is expressed to Loretta Lynne Crowe for the preparation of this
manuscript.

HIGHLIGHTS
Childhood play is the most common cause of pediatric facial
fractures, but motor vehicle accidents cause the most severe
injuries.
There is a high incidence of associated neurocranial injuries
with pediatric facial fractures, which reinforces the importance
of a complete initial assessment.
Facial development is a change not only in size but also in the
structure and function of the face. The result is dynamic
transformation of the manner in which force is dissipated as a
child grows. This is the biologic basis for the protean patterns
of fractures that occur between infancy and adulthood.
The mandible appears resistant, but it is not immune to
abnormalities of growth caused by trauma. Condylar injuries
are most likely to cause facial asymmetry.
The midface is more susceptible to developmental deformities
from even minor trauma.
Rigid fixation with plates and screws is avoided in the care of
children unless the original features cannot be restored by
simpler, less invasive means. These materials are used in short
segments so that crossing more than one suture is avoided.
After septal hematoma is initially ruled out in the evaluation of
a child with a nasal injury, the child is reexamined 3 to 4 days
later, after the swelling has diminished, to determine whether a
displaced nasal fracture is present and necessitates reduction.
Occult nasoethmoidal fracture is suspected when there is
marked flattening of the dorsum.
In the treatment of young children, an acrylic splint is used on
the lower teeth and fixed with circummandibular wires for
alignment of the fracture fragments of the arch and body.
In the treatment of children younger than 13 years who need
open reduction with internal fixation, the presence of unerupted
tooth buds is ascertained, and holes for wires or monocortical
miniplates are drilled in the lowermost margins of the
mandible.
Intermaxillary fixation is limited to 2 to 3 weeks and is
followed by 6 to 8 weeks of use of guiding elastic bands.
The integrity of the medial canthal ligament is evaluated while
the patient is under anesthesia. The examination is made with
an intranasal hemostat and a finger in the medial canthus.
Mobility of the bone to which the tendon attaches indicates the
need for canthopexy.
The easiest mistake to make in managing a pediatric
nasoethmoidal fracture is to set the intercanthal distance too
wide, expecting that the child will grow. An attempt is made at
excessive narrowing of the distance and excessive projection of
the nose.
Late developing periorbital hematoma suggests fracture of the
orbital roof.
With extensive fractures of the orbital floor or demonstrable
muscle entrapment, early surgery is appropriate. With more
isolated injuries, waiting 7 to 10 days may prevent an
unnecessary operation.
Calvarial bone grafts are harvested in two stages in the care of
children younger than 10 years. The neurosurgeon takes a full-
thickness plate off, splits it, and uses the inner table for the
grafts.
CHAPTER REFERENCES
1. Rowe IM, Fonkalsrud EW, O'Neil JA, et al. The injured child. In: Essentials of pediatric surgery.
St. Louis: Mosby, 1995.
2. Koltai PJ, Rabkin D, Hoehn J. Rigid fixation of facial fractures in children. J Craniomaxillofac
Trauma 1995;1:3242.
3. Gussack GS, Lutterman A, Rodgers K, et al. Pediatric maxillofacial trauma: unique features in
diagnosis and treatment. Laryngoscope 1987;97:925930.
4. McGraw BL, Cole RR. Pediatric maxillofacial trauma. Arch Otolaryngol Head Neck Surg
1990;116:4145.
5. Siegel MB, Wetmore RF, Postic WP, et al. Mandibular fractures in the pediatric patient. Arch
Otolaryngol Head Neck Surg 1991;117:533536.
6. Koltai PJ, Amjad I, Meyer D, et al. Orbital fractures in children. Arch Otolaryngol Head Neck
Surg 1995;121:13751379.
7. Koltai PJ, Wood GW. Three dimensional CT reconstruction for the evaluation and surgical
planning of facial fractures. Otolaryngol Head Neck Surg 1986;95:1015.
8. McGuirt WF, Salisbury PL III. Mandibular fractures: their effect on growth and dentition. Arch
Otolaryngol Head Neck Surg 1987;113:257261.
9. Lin KY, Bartlett SP, Yaremchuk MJ, et al. An experimental study of the effects of rigid fixation
on the developing craniofacial skeleton. Plast Reconstr Surg 1991;87:229238.
10. Marshall MA, Chidyllo SA, Figueroa AA, et al. Long term effects of rigid fixation on the growing
craniomaxillofacial skeleton. J Craniofac Surg 1991;2:6368.
11. Bartlett SP, DeLozier JB III. Controversies in the management of pediatric facial fractures. Clin
Plast Surg 1992;19:245258.
12. Posnick JO. Management of facial fractures in children and adolescents. Ann Plast Surg
1994;33:442457.
13. Gruss JS, Mackinnon SE. Complex maxillary fractures: the role of buttress stabilization and
immediate bone grafting. Plast Reconstr Surg 1986;78:922.
14. Shumrick KA, Kersten RC, Kulwin DR, et al. Extended access/internal approaches for the
management of facial trauma. Arch Otolaryngol Head Neck Surg 1992;118:11051112.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

93 CONGENITAL VASCULAR LESIONS
Head & Neck SurgeryOtolaryngology
93




CONGENITAL VASCULAR LESIONS
NORMAN R. FRIEDMAN
RON MITCHELL

N.R. Friedman: Department of Otolaryngology, Children's Hospital, Denver, Colorado.
R. Mitchell: Division of Otolaryngology, Plastic and Reconstructive Surgery, University of New Mexico,
Albuquerque, New Mexico.


Hemangiomas
Management of Hemangiomas
Vascular Malformations
Capillary Malformations and Other Birthmarks
Lymphatic Malformations
Venous Malformations
Arteriovenous Malformations
Associated Syndromes
Chapter References
The diagnosis and management of congenital vascular lesions is complicated by the use
of numerous names to designate individual types of developmental anomalies. For
example, physicians may refer to hemangiomas as either cavernous or strawberry and to
lymphatic malformations as either cystic hygroma or lymphangioma. The term
hemangioma also may be used to describe all congenital vascular lesions. In 1992
Mulliken (1) introduced a classification system that divides vascular anomalies into two
major categories, hemangiomas and vascular malformations, based on both cellular
features and biologic behavior (Table 93.1). Hemangiomas rarely are present at birth,
undergo rapid growth by means of proliferation and then slowly involute. Vascular
malformations always are present at birth, do not proliferate, and do not involute (1). In
1996, the International Society for the Study of Vascular Anomalies adopted Mulliken's
nomenclature for congenital vascular lesions to standardize the literature.

TABLE 93.1. CHARACTERISTICS OF
CONGENITAL VASCULAR LESIONS



HEMANGIOMAS
Hemangiomas are the most common neonatal tumor, with an incidence as high as 10%.
They are more prevalent in caucasians, in females, and in premature infants with a low
birth weight. The most common location is the head and neck (59%) followed by the
trunk (24%) (2). A hemangioma has different life cycle phasesproliferative, involuting,
and involuted (Fig. 93.1; see also Color Plate 32 following p. 496). The proliferative
stage typically lasts 6 to 12 months and is characterized by rapid growth due to
endothelial cell hyperplasia. Hemangiomas involute over a period of several years.
Approximately 50% of these lesions are completely resolved by 5 years of age and 70%
by 7 years. Once involuted, a hemangioma can leave a variety of sequelae including
redundant skin, scarring, and telangiectasia. In rare instances a hemangioma is apparent
in the immediately postnatal period. A hemangioma that is present at birth is referred to
as a congenital hemangioma. The lesion is fully grown at birth, does not proliferate, and
involutes rapidly in the first 2 years of life. Eighty-five percent of all hemangiomas
manifest themselves in the first few weeks of life (2).

FIGURE 93.1. Superficial hemangioma. A:
Proliferating. B: Involution marked by the color fading to
a dull purple. The area, which is a shiny, crimson, is in
the proliferative phase of growth. (See also Color Plate
32 following p. 496) (Courtesy of Department of
Dermatology, University of Texas Medical Branch.)



A hemangioma can be diagnosed with a careful history and physical examination. The
lesion usually is not present at birth. It proliferates during the first year of life and then
decreases in size and involutes. The initial presentation may be an irregular erythematous
macular patch, blanched spot, or localized telan-giectasia surrounded by a pale halo (1).
The appearance of a hemangioma reflects its depth. Superficial hemangiomas are raised
and bright red; subcutaneous hemangiomas have a bluish appearance (Fig. 93.2; see also
Color Plate 33 following p. 496). Some hemangiomas have both a deep and a superficial
component. The diagnosis of hemangioma sometimes is in doubt.

FIGURE 93.2. Bluish coloration characteristic of a deep
hemangioma. (See also Color Plate 33 following p. 496)
(Courtesy of Department of Dermatology, University of
Texas Medical Branch.)



Magnetic resonance imaging (MRI) is the most accurate diagnostic procedure to detect
hemangiomas. They are high-flow lesions with high intensity T2-weighted images and
flow voids on T1- and T2-weighted images. The only other high-flow vascular lesion is
an arteriovenous malformation, which does not enhance on T2-weighted images. In the
future, hematologic and urinary markers are likely to play a greater role in the diagnosis
of hemangiomas. Several biologic markers characteristic for hemangiomas have been
identified. In the proliferative stage, levels of angiogenesis-stimulating proteins (vascular
endothelial growth factor, type IV collagenase, and proliferating cell nuclear antigen)
increase. In the involuting phase, mast cells and a tissue inhibitor of metalloproteinases
are present. Levels of -fibroblast growth factor (FGF) and urokinase are elevated in
both the proliferative and involuting phases (3). Since a proliferating hemangioma has an
elevated level of FGF, a urinary test for FGF may assist in differentiating a
hemangioma from other vascular malformations (4). Complications of hemangioma
include ulceration, airway obstruction, high output cardiac failure, and the psychologic
consequences of a cosmetically deforming lesion of a child (Fig. 93.3; see also Color
Plate 34 following p. 496).

FIGURE 93.3. Rapid lesion growth at the height of the
proliferative phase results in skin ulceration. (See also
Color Plate 34 following p.370) (Courtesy of Department
of Dermatology, University of Texas Medical Branch.)



Kasabach-Merritt phenomenon is a unique condition erroneously associated with
hemangiomas. Patients have had a skin area with reddish or brownish discoloration since
birth that suddenly enlarges into a violaceous plaque. Kasabach-Merritt phenomenon is
characterized by platelet sequestration, ecchymosis, and no female predominance.
Histologic analysis shows that the actual lesion is either kaposiform
hemangioendothelioma or tufted angioma and is different from the involuting type of
hemangioma of infancy (5). Management of Kasabach-Merritt phenomenon is
supportive. Use of heparin is contraindicated because this drug can potentiate tumor
growth. Use of blood products is avoided because these blood products can become
trapped in the lesion and produce rapid tumor enlargement. For anemia, transfusion with
packed red blood cells may be necessary (6).
Hemangiomas, unlike vascular malformations, rarely are associated with true structural
malformations. In 1996, PHACE syndrome was proposed (7); PHACE is an acronym for
posterior fossa malformations, large facial hemangioma, arterial abnormalities,
coarctation of the aorta, cardiac defects, and eye abnormalities. The hemangioma of
PHACE syndrome is a large plaque that can cover several areas on the face in a
nondermatomal pattern. Children with large facial hemangiomas need regular neurologic
examinations and brain imaging studies, preferably MRI, to exclude PHACE syndrome.
A large facial hemangioma also may be associated with subglottic hemangioma. An
increased incidence of subglottic hemangioma has been identified among children with
cutaneous hemangioma involving the beard distribution (preauricular region, chin, lower
lip, and/or neck), although the cause of this association is unclear (8) (Fig. 93.4; see also
Color Plate 35 following p. 496).

FIGURE 93.4. Large, superficial facial hemangioma in
the beard distribution. A deep red color indicates that the
lesion is still in the proliferative phase. (See also Color
Plate 35 following p. 496) (Courtesy of Department of
Dermatology, University of Texas Medical Branch.)



Management of Hemangiomas
Historically the primary plan for management of hemangioma was benign neglect
because most of these vascular abnormalities involute. At present, social issues and new
technology have resulted in more active intervention. Not every lesion regresses
completely, and it is impossible to predict the growth behavior of a hemangioma.
Management of hemangioma depends on the size, anatomic location, and life-cycle stage
of the lesion. One must determine whether a hemangioma is functionally significant, that
is, whether it affects swallowing or vision, or life threatening, that is, associated with high
output cardiac failure or breathing difficulty. Most hemangiomas are neither life
threatening nor function impairing; therefore the indications for instituting treatment are
less clear. Limitation of tumor growth and avoidance of complications are the primary
objectives (9). Because involution occurs, careful risk-benefit analysis is necessary before
treatment is begun. The risk of psychologic trauma of a prominent physical lesion during
the formative years of personality development is an important consideration. Overall, at
least 10% of patients with hemangioma need intervention (10).
The primary medical management of hemangioma is oral prednisone. In a series of 128
patients with either life-threatening or function-impairing tumors, 27% responded well
with tumor shrinkage within 1 month, 46% had cessation in tumor growth but no
shrinkage, and 27% had a poor response. Increasing the dose to 5 mg/kg per day did not
improve the response to therapy (10). If steroid therapy is effective, the general principle
is to continue treatment until involution is well established (8 to 10 months) (6). Infants
are carefully monitored for the side effects of steroids, which include
immunosuppression, growth retardation, moon facies, and gastric ulcers.
For corticosteroid-resistant hemangioma, therapeutic modalities include intralesional
steroids, interferon alfa-2a, or surgery. Intralesional injections are restricted to small,
localized lesions and can be repeated every 6 weeks. Periorbital injections are avoided
given the risk of retinal artery thrombosis and blindness. Interferon alfa-2a is
administered in a daily subcutaneous injection (13 million U/m
2
/day) for 6 months or
longer. Side effects include a low-grade fever, an increase in levels of liver
transaminases, transient neutropenia, and anemia. These effects reverse once treatment is
discontinued. Because spastic diplegia also is a possible side effect of interferon, a
neurologist examines these infants on a regular basis during therapy. In a prospective
study involving 20 patients with hemangiomas who received daily injections of
recombinant human interferon alfa-2a, 90% of the tumors shrank at least 50% within 8
months. The investigators recommended continuing therapy for 9 to 14 months to prevent
relapse (11). Once involution has started, the patient is treated expectantly. If regression
has not occurred by the age of 5 years, the cosmetic result is less likely to be satisfactory,
and surgical intervention is reasonable (2). The management principle is to excise deep
lesions that are not involuting quickly as long as the surgical outcome will have a
cosmetic outcome similar to natural involution (9).
Optimal treatment for superficial hemangioma is photocoagulation. During the early
proliferative phase, these lesions can be managed by means of laser therapy with a
flashlamp pumped pulsed dye laser. Laser treatments are repeated every 4 to 6 weeks
until the superficial component of the lesion has resolved. Because the pulsed dye laser
beam at 585 nm, penetrates only 1.2 mm of tissue, only the superficial aspect of the
lesion is affected. Laser therapy is ineffective for deep hemangioma.
Management of subglottic hemangiomas depends on the size of the lesion and the extent
of airway compromise. Some lesions never reach a size that obstructs the airway. Other
lesions produce inspiratory or expiratory stridor. Systemic steroids are used to prevent
progression of the lesion and to reduce airway obstruction. For patients with severe
respiratory problems despite administration of oral glucocorticoids, the therapeutic
options include intralesional steroid injection, subcutaneous injection of interferon alfa-
2a, and surgery. The safest surgical option is tracheotomy. Once the lesion has involuted
sufficiently, the tracheostomy is removed. Excision of the lesion by means of laser
therapy may lead to long-term subglottic stenosis among as many as 20% of patients
(12). Primary resection also carries risk of stenosis.
VASCULAR MALFORMATIONS
Vascular malformations are the second major category of congenital vascular lesions.
Vascular malformations always are present at birth, although they may not become
apparent for several months or years. They do not proliferate nor do they involute. They
grow commensurately with the patient and grow rapidly only with hormonal changes,
trauma, or infection. These lesions occur when abnormal morphogenesis involves
vascular channels. The lesion is not a tumor because neither cellular hyperplasia nor
cellular proliferation occurs. Vascular malformations enlarge by means of hypertrophy of
existing cells and not the cellular hyperplasia of hemangioma. Vascular malformations
are characterized by normal endothelial cell turnover and a normal mast cell count (2).
Two subcategories of vascular malformations are based on the rate of blood flow through
the lesion. Low-flow lesions include capillary malformations, venous malformations,
lymphatic malformations, and a combined type that has a mixture of either two or three
of the low-flow lesions, such as venous-lymphatic malformation. High-flow lesions
include arterial malformations and arteriovenous malformations (Table 93.2) (1).

TABLE 93.2. VASCULAR MALFORMATIONS



Capillary Malformations and Other Birthmarks
Capillary malformations, better known as port-wine stains, are one of the more common
vascular anomalies. These malformations are present at birth, gradually darken, and may
even produce soft-tissue hypertrophy that gives the appearance of cobblestoning as the
patient ages (Fig. 93.5; see also Color Plate 36 following p. 496). Capillary
malformations must be differentiated from nevus flammeus, a more common vascular
birthmark that is a venular malformation. Nevus flammeus lesions are also known as
angel kiss (glabella), stork bite (nape of the neck), or salmon patch. The incidence
approaches 40%, and the lesions are most common on the neck followed by the eyelids
(13). These lesions have an irregular outline with distinct margins and a pale red or
salmon color (14). Nevus flammeus lesions necessitate no active management and
usually fade within the first year of life (Fig. 93.6; see also Color Plate 37 following
p.496). The neck lesions tend to be more persistent (1). A nevus flammeus that persists
for more than 1 year most likely is a capillary malformation (15).

FIGURE 93.5. A: Capillary malformation in an
adolescent. B: Capillary malformation in an adult.
Cobblestoning is present. (See also Color Plate 36
following p. 496) (Courtesy of Department of
Dermatology, University of Texas Medical Branch.)



FIGURE 93.6. Nevus flammeus lesion of the glabella.
(See also Color Plate 37 following p. 496) (Courtesy of
Department of Dermatology, University of Texas
Medical Branch.)



Capillary malformations are located in the cutaneous superficial vascular plexus and are
made up of capillary and postcapillary venules (16). They have an equal sex distribution.
Most occur in the head and neck, 85% having a unilateral dermatomal distribution (17).
Intervention is indicated because of commensurate growth with the patient and evolution
from a flat lesion with uniform color to a deeply colored, raised lesion that leads to
progressive cosmetic deformity. A pulsed dye laser at 585 nm is used extensively to
manage capillary malformation among infants. Selective destruction of the abnormal
vessels without injuring the overlying skin is the goal of therapy. The advantage of use of
a 585-nm wavelength is selective energy absorption by oxyhemoglobin, which confines
the laser energy to the vessel walls (18). The response of the malformation to laser
therapy varies with anatomic location. Centrofacial and V2 dermatome lesions respond
less favorably to laser therapy (19). Laser treatment leads to lightening of the lesions
among 80% of patients. In selected cases it is possible to excise the capillary
malformation and achieve primary closure. However, scar hypertrophy and discoloration
continue to be problems.
Lymphatic Malformations
Lymphatic malformations occur when lymphatic sacs fail to communicate with lymphatic
vessels. These lesions may be macrocystic, microcystic, or a combination of the two.
They can occur anywhere in the body, but the head and neck is the most common site.
The clinical presentation of lymphatic malformations ranges from a localized cervical
lesion to an extensive lesion involving the neck, the floor of the mouth, the tongue, and
the face. Lymphatic malformations most commonly grow commensurately with the
patient. Nevertheless, periods of rapid expansion can occur and are associated with
infection, bleeding, or trauma. Spontaneous regression of these lesions is not frequent.
Because they are congenital and the lesions persist through life, one would expect
deflation not complete resolution. Magnetic resonance imaging is the study of choice for
the diagnosis of a lymphatic malformation and for preoperative planning. At MRI,
lymphatic malformations appear as a septated mass with low-intensity signal on T1-
weighted sequences and high-intensity signal on T2-weighted sequences but without flow
voids. A staging system has been proposed to divide lymphatic malformations into stages
according to their anatomic distribution (20) (Table 93.3).

TABLE 93.3. STAGING SYSTEM FOR
LYMPHATIC MALFORMATIONS



Surgical resection is the best therapy for lymphatic malformations. Sclerotherapy,
incision and drainage, aspiration, and radiation therapy have been tried unsuccessfully.
From a prognostic point of view, the disease can be divided into the following two
categories: Stage I infrahyoid disease, which has a good prognosis, and Stages II through
IV suprahyoid disease, which has a less favorable prognosis. Infrahyoid disease is
generally macrocystic and once was called cystic hygroma. This type of disease is well
circumscribed, discrete, and usually can be excised totally in one procedure. Suprahyoid
disease is microcystic, infiltrates surrounding soft tissue, and can invade the oral cavity,
the lip, the tongue, the cheek, and the face. The presence of bilateral suprahyoid disease
is a harbinger of airway problems. Excision of suprahyoid disease is inevitably
incomplete, and several surgical resections may be needed. In a review of 191 patients
with lymphangiomas over a 25-year period (21), 45% of patients underwent observation
an average of 5 years before surgical intervention, and only 5 patients (2.6%) needed
urgent intervention. Forty-eight percent of lesions were located in the head or neck
region. Recurrence rates according to management were 100% after aspiration and
injection, 40% after incomplete excision, and 17% after macroscopically complete
excision.
A nonsurgical alternative in the management of lymphatic malformations is
administration of OK432, a lyophilized, low-virulence strain of Streptococcus pyogenes.
One study of this form of therapy showed that the cystic composition of the malformation
determined the efficacy of OK432. Macrocystic lesions had a 92% response rate, whereas
the response rate for microcystic lesions was only 44% (22). These favorable results have
been repeated only in therapy for macrocystic lesions (23). The lesions for which this
therapy would be most useful, however, are unresectable microcystic lesions that invade
the floor of the mouth, the tongue, and the face. These do not seem to respond well to
OK432.
Venous Malformations
Venous malformations are soft, compressible, nonpulsatile masses of variable size. The
histologic features are dilated vascular channels lined by normal endothelium. Venous
malformation can present as an isolated skin varicosity or as a complex lesion infiltrating
various tissue planes. The lesions are common on the head and neck, particularly the lips
and cheeks. Intraosseous venous malformations can occur in the mandible, maxilla, or
zygoma. Superficial lesions have a bluish color, while deeper ones can have normal
overlying skin. When the lesion is in a dependent position, blood engorgement produces
transient enlargement during a Valsalva maneuver or with compression of the jugular
vein. Sudden growth can occur after trauma or in association with hormonal changes
(15). The low-flow characteristics of these lesions can cause tissue thrombosis that is
visible as phleboliths on plain radiographs. These phleboliths can produce localized pain
and tenderness. In most cases, reassurance and explanation of the course of the lesion
without intervention is all that is necessary. Therapy is needed for symptomatic lesions
and lesions that cause marked cosmetic deformity. Treatment options include
sclerotherapy and surgical resection. Before resection, MRI is helpful to assist in surgical
planning. Unfortunately, venous malformations have a tendency to recur and can enlarge
substantially after partial resection.
Arteriovenous Malformations
Arteriovenous malformations are abnormal communications between arteries and veins
that bypass the capillary bed. Most arteriovenous malformations become clinically
apparent in the second and third decades of life. These fast-flow lesions are rarer than
slow-flow vascular anomalies. Characteristically, an arteriovenous malformation is a
pulsatile mass with an associated thrill or bruit. The patient may report throbbing or
stabbing pain or pulsatile tinnitus. In some instances, overlying skin discoloration and
tissue hyperthermia occur (1). Arteriovenous shunting is confirmed by the presence of a
bruit found at auscultation or Doppler measurement. Skin necrosis, ulceration, bleeding,
and heart failure are recognized complications. Diagnostic imaging is a critical part of the
evaluation of these lesions. Magnetic resonance imaging shows no enhancement on T2-
weighted images and flow voids on both T1-weighted and T2-weighted images.
Angiography shows dilatation and lengthening of arteries and early shunting of enlarged
veins (24). No therapy is necessary for asymptomatic lesions. When complications occur,
surgical therapy with previous embolization and total resection of the arteriovenous
malformation is necessary.
Associated Syndromes
A variety of syndromes are associated with vascular malformations. One of the well
known syndromes is Sturge-Weber. In this syndrome, a facial capillary malformation
(port-wine stain) in-volving the ophthalmic division of the trigeminal nerve is associated
with ipsilateral vascular malformation of the leptomeninges and eye (25). The choroidal
malformation in the eye causes glaucoma among 30% of patients. The vascular
malformation of the central nervous system produces progressive ischemic atrophy and
cortical calcification. The result is seizures, focal neurologic deficits, and developmental
delay (26). In Klippel-Trenaunay syndrome, cutaneous capillary malformation with
underlying venous and lymphatic malformation is associated with skeletal overgrowth of
a limb and possible growth retardation (15). Parkes Weber is a similar syndrome except
that an arteriovenous rather than a venous malformation is the main vascular anomaly.
Blue rubber bleb is a rare condition of multiple venous malformations of the skin and
gastrointestinal tract. The cutaneous lesions are bluish and rubbery, and the
gastrointestinal lesions can cause bleeding and anemia (1) (Fig. 93.7; see also Color Plate
38 following p. 496). Although not part of a syndrome, both capillary malformation and
hemangioma over the lumbar spine have been associated with spinal cord anomalies
(1,27).

FIGURE 93.7. Blue rubber bleb. (See also Color Plate
38 following p. 496) (Courtesy of Department of
Dermatology, University of Texas Medical Branch.)




HIGHLIGHTS
Hemangiomas are not present at birth. They undergo rapid
growth proliferation and then slowly involute. Superficial
hemangiomas are raised and bright red; subcutaneous
hemangiomas have a bluish appearance. Some hemangiomas
have both a deep and superficial component.
An increased incidence of subglottic hemangiomas has been
identified among children who have cutaneous hemangiomas
involving the beard distribution (preauricular region, chin,
lower lip, and neck).
Vascular malformations are always present at birth; they do not
proliferate and do not involute.
Vascular malformations are divided into two subcategories
according to the rate of blood flow through the lesion. Low-
flow lesions include capillary malformations, venous
malformations, lymphatic malformations, and a combined type,
which is a mixture of two or three of the low-flow lesions, such
as venous-lymphatic malformation. High- flow lesions include
arterial malformation and arteriovenous malformation.
Venular malformations are better known by their common
namesangel kiss (glabella), stork bite (nape of the neck), and
salmon patch. The incidence is close to 40%, and the lesions are
most common on the neck followed by the eyelids. These
lesions necessitate no active management and usually fade
within the first year of life.
Capillary malformations, better known as port-wine stains,
darken and can even produce soft-tissue hypertrophy as the
patient ages. The response of the malformation to laser therapy
varies with anatomic location.
Lymphatic malformations grows commensurately with the
patient, although periods of rapid expansion can occur and are
associated with infection, bleeding, or trauma. These lesions
can be macrocystic, microcystic, or a combination of the two.
CHAPTER REFERENCES
1. Mulliken JB, Young AE. Vascular birthmarks hemangiomas and malformations. Philadelphia:
WB Saunders, 1988.
2. Finn MC, Glowacki J, Mulliken JB. Congenital vascular lesions: clinical application of a new
classification. J Pediatr Surg 1983;18:894900.
3. Takahashi K, Mulliken JB, Kozakewich HPW, et al. Cellular markers that distinguish the phases
of hemangioma during infancy and childhood. J Clin Invest 1994;93:23572364.
4. Folkman J. Clinical applications of research on angiogenesis. N Engl J Med 1995;333:17571763.
5. Enjolras O, Wassef M, Mazoyer E, et al. Infants with Kasabach-Merritt syndrome do not have
true hemangiomas. J Pediatr 1997;130:631640.
6. Mulliken JB, Boon LM, Takahashi K, et al. Pharmacologic therapy for endangering hemangiomas.
Curr Opin Dermatol 1995;109113.
7. Frieden IJ, Reese V, Cohen D. PHACE syndrome: the association of posterior fossa brain
malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and
eye abnormalities. Arch Dermatol 1996;132:307311.
8. Orlow SJ, Isakoff MS, Blei F. Increased risk of symptomatic hemangiomas of the airway in
association with cutaneous hemangiomas in a beard distribution. J Pediatr 1997;131:643646.
9. Management of hemangiomas. Pediatr Dermatol 1997;14:5783.
10. Enjolras O, Gelbert F. Superficial hemangiomas: associations and management. Pediatr Dermatol
1997;14:173179.
11. Ezekowitz RAB, Mulliken JB, Folkman J. Interferon Alfa-2a therapy for life-threatening
hemangiomas of infancy. N Engl J Med 1992;326:14561463.
12. Sie KCY, McGill T, Healy GB. Subglottic hemangioma: ten years' experience with the carbon
dioxide laser. Ann Otol Rhinol Laryngol 1994;103:167172.
13. Jacobs AH, Walton RG. The incidence of birthmarks in the neonate. Pediatrics 1976;58:218222.
14. Pratt AG. Birthmarks in infants. Arch Dermatol 1967;67:302305.
15. Burns AJ, Kaplan LC, Mulliken JB. Is there an association between hemangioma and syndromes
with dysmorphic features? Pediatrics 1991;88:12571267.
16. Smoller BR, Rosen S. Port-wine stains: a disease of altered neural modulation of blood vessels?
Arch Dermatol 1986;122:177179.
17. Tallman B, Tan OT, Morelli JG, et al. Location of port-wine stains and the likelihood of
ophthalmic and/or central nervous system complications. Pediatrics 1991;87:323327.
18. Haedersdal M. Cutaneous side effects from laser treatment of the skin: skin cancer, scars, wounds,
pigmentary changes, and purpurause of pulsed dye laser, copper vapor laser and argon laser.
Acta Derm Venereol 1999;207:232.
19. Renfro L, Geronemus RG. Anatomical differences of port-wine stains in response to treatment
with the pulsed dye laser. Arch Dermatol 1993;129:182188.
20. de Serres LM, Sie KCY, Richardson MA. Lymphatic malformations of the head and neck: a
proposal for staging. Arch Otolaryngol Head Neck Surg 1995;121:577582.
21. Alqahtani A, Nguyen LT, Flageole H, et al. 25 years' experience with lymphangiomas in children.
J Pediatr Surg 1999;34:11641168.
22. Ogita S, Tsuto T, Nakamura K, et al. OK-432 therapy in 64 patients with lymphangioma. J
Pediatr Surg 1994;29:784785.
23. Greinwald JH, Burke DK, Sato Y, et al. Treatment of lymphangiomas in children: an update of
picibanil (OK-432) sclerotherapy. Otolaryngol Head Neck Surg 1999;121:381387.
24. Dubois J, Garel L. Imaging and therapeutic approach of hemangiomas and vascular malformations
in the pediatric age group. Pediatr Radiol 1999;29:879893.
25. Powell J. Update on hemangiomas and vascular malformations. Curr Opin Pediatr 1999;11:457
463.
26. Burrows PE, Laor T, Paltiel H, et al. Diagnostic imaging in the evaluation of vascular birthmarks.
Pediatr Dermatol 1998;16:455488.
27. Albright AL, Gartner JC, Wiener ES. Lumbar cutaneous hemangiomas as indicators of tethered
spinal cords. Pediatrics 1989;83:977980.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

94 IMAGING TECHNOLOGY IN OTOLARYNGOLOGY
Head & Neck SurgeryOtolaryngology
94




IMAGING TECHNOLOGY IN
OTOLARYNGOLOGY
MARVIN P. FRIED
RICHARD V. SMITH

M.P. Fried and R.V. Smith: Department of Otolaryngology, Albert Einstein College of Medicine, and
Montefiore Medical Center, Bronx, New York.


Image Guidance
Image Guidance for Biopsy
Image Guidance for Endoscopic Sinus Surgery
Image Guidance and Staging Endoscopy
Anatomic and Surgical Simulation
Digital Camera Applications
Advances in Endoscopy
Diagnostic Virtual Endoscopy
Surgical Adjuvants
Chapter References
Surgery is a highly visual endeavor. Although many senses are put in play when
procedures are performed, the visual perspective is critical. This begins when the patient
is first encountered, the history is obtained, and the examination is undertaken. It is
supplemented with devices such as an endoscope and expanded with radiographs and
histologic specimens. With advances in instrumentation, optical devices, and
computerization, there exists the opportunity to develop images that are more detailed or
generated from a new perspective, such as closer to the surface or from anatomic vantage
than cannot be gained with patient positioning. Regions can be viewed that require small
devices for access. Three-dimensional reconstructions are possible that allow
manipulation of the surgical environment before and during the operation. The view of
the surgical field can be supplemented with a radiographic rendition that localizes the
operative site in relation to surrounding critical structures or the extent of the pathologic
condition.
This chapter describes advances in the realm of visual renditions, optical devices, and
integrated imaging that hold exciting possibilities for otolaryngologists. Most of these
will be part of daily routine in the near future, and many are currently available.
Prospects for technologies beyond the horizon are based on the development of
applications that are difficult to imagine (1). The merging of imaging and data from a
number of sources is predicated on digitalization of information that can then be stored
and manipulated into formats that serve specific needs. These packets of data can be
integrated into a usable whole-data set that is derived from disparate sources that can be
anatomic, radiologic, physiologic, or pathologic. Images can be obtained with endoscopic
devices that produce a photograph-like rendition or with lasers that generate a
spectrographic display that specifically characterizes the tissue in question.
Diagnostic imaging can be performed rapidly enough for noninvasive evaluation of
cardiac flow and function (2). Rapid assessment of other physiologic motion, such as
vibration of the vocal folds, is feasible. Functional magnetic resonance imaging (MRI)
can be used to map brain activity during ordinary activity. Dyslexia can be classified with
functional MRI brain-mapping studies (2). Positron emission tomography generates
images through labeling of radioactive glucose, which is metabolized differentially by
normal and neoplastic cells (Fig. 94.1). It has been used successfully to identify tumors of
the head and neck (3,4). Positron emission tomography can be integrated into the
anatomic rendition for accuracy in tumor localization. Molecular imaging can take
functional testing to a greater level of refinement by allowing specific labeling of
subcellular or even genetic material to fingerprint tissue abnormalities. Displayed with
the anatomic rendition, highly specific images can be made to delineate the presence and
extent of pathologic conditions. The images can be manipulated into a format that allows
production of a streaming, fly-through rendition that is a virtual endoscopic image not
limited by the presence of a lumen or anatomic obstruction. These are but a few of the
possibilities that will be available to otolaryngologists in the near future.

FIGURE 94.1. Positron emission tomographic scan
shows T4N0 squamous cell carcinoma of the maxillary
sinus invading the orbit. The lesion is shown in the axial,
coronal and sagittal planes.



IMAGE GUIDANCE
Minimally invasive surgery is no more than reaching surgical sites without excessive
disruption of normal tissue. Otolaryngologists have been able to approach the middle ear,
nose and paranasal sinuses, and upper aerodigestive tract rapidly with standard
microscopic and endoscopic procedures. Other anatomic regions require sophisticated
techniques to reach pathologic conditions; in these procedures the degree of morbidity is
related to access rather than the disease for which the patient is being treated. In some
procedures, although the access may be rapid, such as in endoscopic sinus surgery (ESS),
the risks to the surrounding structures may be great, particularly if the structures are not
in direct view or are distorted by the disease process. For most of these operations,
radiographs are obtained before the procedure so that the abnormality can be visually
described. Radiography has been shown to be valuable in the evaluation of disease of the
head and neck by increasing the accuracy of clinical assessment (5). Lesions of the base
of the tongue and the pharynx are particularly sensitive to radiography. Sinus
abnormalities cannot be evaluated without the appropriate radiographs. As many as 50%
of cases of cancer of the head and neck can be staged at both the primary and the nodal
sites (5).
Image guidance is the technique whereby images are used to provide information about
the location or progress of the procedure being performed. This information keeps the
surgeon aware of tissue changes or anatomy and allows fine control of the operation.
Images can be obtained with a number of modalities, such as ultrasonography, computed
tomography (CT), and MRI.
Image Guidance for Biopsy
One of the most common and useful surgical procedures is biopsy. Often biopsy is
performed on an apparent lesion that lies on the mucosa or in it. Neck masses usually are
palpable, and placing a fine needle for aspiration and cytologic examination is not a
clinical challenge. However, circumstances arise when the mucosal site is not obvious or
the neck mass not readily palpable. In these instances, imaging is needed.
Ultrasonography, CT, and MRI have been used to guide location of the biopsy device or
to maximize the likelihood of obtaining representative tissue and disclosing the limits of
the lesion.
Ultrasonography has been used for years and has the benefits of no x-ray exposure to the
patient or physician and portability of the imaging device (6). Bearcroft et al. (5) used
ultrasound guidance to perform 60 biopsies on 52 patients with neck masses. For all
patients, the histologic diagnosis was compatible with subsequent clinical, radiologic,
surgical, or autopsy findings. Robbins et al. (7) also were able to use both CT and
ultrasonography for fine-needle or core-needle biopsy on all patients in a study who had
inaccessible and deep space lesions. The investigators found the technique expeditious,
safe, and accurate (7). Other investigators (8) have had similar experience with image
guided biopsy, often with avoidance of open procedures when there was a question of
inflammation versus neoplasia. Ultrasound-guided biopsy is particularly valuable in the
care of patients who have undergone surgery or radiation therapy or whose masses are
situated deep to the vascular, neural, and bony structures in the region (9). Moreover, for
surgical candidates, preoperative identification of the tumor and the possible histologic
findings allows operative planning and patient counseling.
Imaging may not help differentiate scar from tumor or radiation edema from infection.
Anatomic features can be distorted by disease or previous intervention. Lesions of the
base of the skull are difficult to reach, and extensive operations are needed to remove the
pathologic lesion. Preoperative planning is critical in patient care. The biopsy approach to
these sites can be by percutaneous (10) or transoral techniques and usually necessitates
only local anesthesia, occasionally with sedation.
Both ultrasonography and CT entail real-time acquisition of images while a procedure is
being performed. Ultrasonography is of limited value when bone abuts the area in
question (7). It often is the best modality when thyroid masses are aspirated (9). Solid
areas in cystic masses can be evaluated, and nodules in glands with diffuse disease or that
have been treated with surgery or radiation therapy can be sampled. There is no
consensus on the use of routine ultrasound-guided biopsy to evaluate thyroid disease
because the decision to perform surgery is not predicated on one variable in most cases.
In more generalized cases, ultrasound images can be difficult to interpret. Computed
tomographic images are more familiar to surgeons but must be generated before an
operation. Radiographic imaging during a surgical procedure exposes the patient,
surgeon, and operating room personnel to additional radiation (Fig. 94.2).

FIGURE 94.2. A: Soft-tissue window computed
tomographic (CT) scan of a tumor of the left
infratemporal fossa. B: Bone-window CT scan shows
tumor of the left infratemporal fossa with biopsy needle
in place.



Although CT provides excellent resolution of bone, it has less value in the display of soft-
tissue structures than do other imaging techniques. Magnetic resonance imaging produces
a display of soft-tissue structures that is familiar to the surgeon without the use of
ionizing radiation. Magnetic resonance imaging also has been used for intervention (11)
(Fig. 94.3). In a conventional MRI device, however, access to the patient is limited
because the closed, tubular configuration of the magnet inhibits any meaningful type of
extensive procedure. Early use of MRI fine-needle aspiration necessitated placement of a
percutaneous needle, sliding the patient into the bore of the magnet, obtaining an image,
and taking the patient out of the magnet for repositioning of the needle. The patient was
placed back into the MRI for more images until precise needle location was achieved
(12). Open-configuration scanners now can be used in which the surgeon has direct
access to the patient and in which procedures with local and general anesthesia can be
performed (13,14) (Fig. 94.4). The units eliminate the inconvenience of adjusting the
patient to the imaging volume during biopsy and provide real-time images with which
online planning of biopsy trajectory is feasible. Early experience with interventional MRI
suggests that this technology may improve localization, increase the yield of image-
directed biopsy, decrease the rate of repeated procedures, and allow biopsy of difficult-to-
reach areas (15) (Fig. 94.5).

FIGURE 94.3. Magnetic resonance imagingguided
biopsy of deep lobe tumor in left parotid gland.



FIGURE 94.4. Open magnetic resonance therapy unit.



FIGURE 94.5. Surgeon within the bore of the open
magnet facing two liquid crystal display units that can
depict both endoscopic and magnetic resonance images.



The main difficulties with open MRI are related to the need for nonferromagnetic
instrumentation and equipment and the high cost. General anesthesia can be delivered in
these MRI environments, but local anesthesia with sedation is all that is needed for most
biopsy procedures. Surgical instruments are made from low-iron-content stainless steel,
copper, or titanium (16). Surgical instruments made from brass, ceramic, and carbon-
fiber have an additional advantage in that they have the least imaging artifact on
intraoperative MR images. Imaging of the device in the surgical field provides image
guidance in most biopsies, regardless of imaging modality. Computerized tracking of
instruments is needed in complex operations to visualize placement of the instrument and
the trajectory. This interactive method allows the surgeon to determine the imaging plane
during the procedure. The position of the instruments is recognized by infrared light-
emitting diodes (LEDs) mounted on the instrument and sensed by cameras in the bore of
the magnet. A computer calculates the position of the instrument tip and displays it on
images viewed by the surgeon in the magnet area. Acquisition of most images takes 14
seconds. Much shorter acquisition times can display images with greater signal-to-noise
ratios, but they often are adequate for a simple display of instrument localization.
All of the image-guided techniques have learning curves. The greater the complexity of
the device, the longer it takes to learn the details, and often the more people are involved.
Interactive MRI is probably the most personnel-intensive modality. Skilled radiologists
and technicians are needed for optimum performance and yield (16). The overwhelming
shortcoming of the interventional open MRI units is the exceptional cost; an entire
surgical suite often must be designated for the procedure (17).
Image Guidance for Endoscopic Sinus Surgery
The use of imaging, most often CT, is a requisite for ESS. The impetus comes from the
key-hole nature of the surgery, the two-dimensional view provided by a nasal endoscope,
and the complex surrounding anatomic features. Endoscopic sinus surgery can be
technically challenging because of the proximity of the central nervous system and orbital
structures and because of the anatomic variations encountered. Extensive disease, such as
sinonasal polyposis, and the fairly frequent need to perform revision surgery in a field
that has been altered can add to the surgical complexity and risks of the procedure (18).
By mentally integrating the radiographic information with the operative field, as
visualized during ESS, the surgeon is continuously aware of location during the
procedure.
Image guidance during ESS has been developed to combine CT renditions with the
endoscopic display to monitor the location of various instruments in the operative field.
The development of these systems has been rapid. Initially designed for neurosurgical
stereotactic navigation, use of these techniques in operations on the paranasal sinuses
followed (19). Probes are mounted on articulated arms that allowed precise determination
of the tip of the arm. Skin markers (fiducials) placed on the patient during CT or
anatomic points are used to align the images with the patient (20). After this registration
process, the probe is used to identify any anatomic point throughout the CT data set and
mark such points on coronal, axial, and sagittal views. It is appropriate to corroborate the
accuracy of the device by means of identification of known anatomic landmarks in a
patient with the CT navigation points displayed by the computer. Discrepancies must be
rectified before the procedure is begun or whenever they are found during an operation
(Fig. 94.6).

FIGURE 94.6. A: Computed tomographyguided
device. B: Computed tomographyguided device used in
operating room. C: Screen of CT image-guided device
with cross hairs depicts the frontal recess and
opacification of the left frontal sinus.



Reports of clinical applications have come from a number of investigators using different
devices (20,21,22 and 23). Articulated arms have given way to cord-attached and
cordless handpieces. Optical tracking systems use LEDs sensed by cameras or reflective
spheres that replace the LEDs. Probes used at first simply to display location have been
modified to suction tips that are straight, angled, or curved to function in the surgical
field and reach distant or tortuous areas. Attachments can be added to common
instruments, such as grasping and through-biting forceps and microdbriders (24). The
goal is to have a system that is so well integrated to the surgical environment that it
becomes another instrument rather than a procedure unto itself. It is certain that this goal
will be met with modification of the tools now available (Fig. 94.7).

FIGURE 94.7. Microdbrider with radiofrequency
attachment for tracking an image-guided device.



Computed tomographic images are obtained before surgery and transferred to the
computer stationed in the operating room. The images are displayed on the computer
screen in axial, coronal, and sagittal planes. The endoscopic image also can be shown on
the same screen, or a full-screen rendition can be projected. Although the radiographic
images are in real time at surgery, in actuality they represent the disease process at the
time they were obtained. Alterations due to surgical manipulation are not shown. If the
scans are obtained before the operation, such as weeks in advance and stored for later
use, the disease may look different at the operation. For most operations, this limitation is
not of great consequence because the bone perimeters of the sinuses are the main
concern, and those are stable over time. If precise delineation of the pathologic condition
is needed, the scans can be obtained immediately before the operation.
The impressions of investigators who have used them extensively are that these devices
increase the precision of the procedure as well as confidence of location (20,21,22,23 and
24). Roth et al. (25) suggested the following criteria for image guidance: (a) accuracy of
2 to 3 mm be maintained; (b) the second CT study before the procedure be eliminated; (c)
the computer update head movement under local or general anesthesia; (d) sensors be
applied to suction devices and dissecting instruments to increase flexibility; (e) the device
be easily operated by the surgeon to eliminate employment of a technician. Operative
time may increase, but this may represent more extensive surgical intervention and not
the additional time needed to set up the guidance system.
The indications for use of these systems are evolving. Patients who need revision
operations and those with extensive polyposis or erosive disease can benefit. Difficult
regions such as the frontal and sphenoid sinuses are particularly appropriate. Whether
routine use in all procedures is warranted cannot be determined at present. In training
situations, the use of image guidance is of a great advantage for attending surgeons and
residents. The surgeon can be reassured about location. The resident becomes familiar
with anatomic features and alterations and can correlate the endoscopic view with the
radiographs.
Although ESS is an ideal situation for use of intraoperative MRI-guided surgery, it has
not been studied extensively. Interventional MRI units are scarce, and it is difficult to
obtain MRI-compatible surgical instruments. Fried et al. (26) described their experience
with the use of ESS with real-time MRI intraoperative guidance to treat patients under
general anesthesia (Fig. 94.8). Twelve patients underwent surgery, 11 for chronic
rhinosinusitis and 1 for a tumor. Four of the operations were revision procedures. No
complications were encountered. The endoscopic display and MR images were available
at the surgical field. The surgeon controlled the image plane, and the MR images were
updated in as little as 14 seconds. The intraoperative data reflected the tissue changes
during surgery and provided navigation information and optimum information for
surgical guidance. Although the MRI limited operating room size and the instruments and
monitoring equipment needed to be MRI-compatible, the utility of interventional MRI
was apparent. As with CT-guided procedures, patients who need revision surgery, those
who have anatomic variations, and those who have disease in regions such as close to the
optic nerve, are candidates for procedures with MRI guidance. Patients with sinonasal
tumors that can be approached endoscopically can be ideally served as well, because the
real-time renditions reflect resection of the lesion.

FIGURE 94.8. Magnetic resonance imaging tracking of
endoscopic sinus surgery. Icon is present in right
ethmoidal sinus.



Endoscopic sinus surgery was one of the first procedures to be performed under MRI
guidance in an open magnet because of the potential benefits of real-time visualization.
The development of CT-based devices for sinus surgery supplanted MRI because CT is
better in the operating room environment. Magnetic resonance images, however, can
depict anatomic relations in true three-dimensional planes rather than the reconstructed
sagittal plane. This will prove to be an advantage in the complex head and neck region.
Because MRI does not involve radiation exposure, it is better suited for prolonged
intraoperative guidance. The temperature sensitivity of MRI can show alterations induced
by heat and cold and thereby reflect tissue effects of laser and cryotherapy manipulations.
Shortcomings and obstacles do exist. Specialized instruments are expensive and are
individually manufactured. Some magnet compatible instruments can produce imaging
artifacts. Each image must be made and shown individually. When several sequences are
needed, such as both T1-weighted and T2-weighted images, additional time is needed
that increases the duration of surgery. As technology advances, these concerns will be
addressed.
Image Guidance and Staging Endoscopy
The initial and critical evaluation of a patient with a suspected malignant tumor of the
head and neck entails endoscopy and biopsy to stage the tumor. Most often, radiographic
studies are obtained before endoscopy to help assess depth of tumor invasion not obvious
at routine examination. This initial evaluation is critical because it predicates the
treatment modalities and is the basis of outcomes assessment. With an open,
interventional MRI unit, it is possible to perform endoscopy and imaging concomitantly.
The benefits of MRI for soft-tissue contrast, freedom from beam-hardening artifacts, and
multiplanar imaging are particularly suitable for endoscopy. Gradient sequencing allows
vascular delineation and gadolinium contrast material enhances tumor margins. Nodal
disease can be more accurately staged when imaging is combined with physical
examination. Clinical examination and endoscopy can be hindered by a bulky tumor mass
or simply not seen because of minimal or no mucosal abnormality. Simultaneous imaging
with endoscopy can direct biopsy and offers increased accuracy.
The most important limitation of image guidance with staging endoscopy is difficulty
developing endoscopes and instruments that are MR safe and compatible. The limited
number of interventional MRI units in existence does not motivate instrument companies
to expend resources on development of devices of unique alloys that have little marketing
potential. We and our colleagues have developed a laryngoscope, biopsy forceps, suction
cannulas, and a universal bronchoscope-esophagoscope (27) (Fig. 94.9). Testing of a
number of metals is necessary before the best material is found that is suited for the task.
The biopsy tools must be able to obtain adequate tissue in the depths and margins of the
lesion to sample the extent of the tumor. New designs allow tissue acquisition without
tissue disruption. Applications for humans are yet to be developed.

FIGURE 94.9. A: Magnetic resonance imaging (MRI)
compatible nonferrous laryngoscope. B: Magnetic
resonance imagingcompatible biopsy forceps. C: Pig
head with MRI-compatible laryngoscope and biopsy
forceps in place. There is no image distortion, and
placement of the biopsy forceps is evident.



ANATOMIC AND SURGICAL SIMULATION
The learning of anatomy and the gaining of surgical skills have classically been based on
the use of cadaveric models. Anatomic dissections are of critical value, but specimens are
difficult to obtain. After dissection is completed, the specimen is available for further
study but cannot be altered for different approaches or teaching goals. This is even more
the case when surgical procedures are taught. Once done, a procedure is nearly
impossible to undo or redo. Trial and error are impossible, and training more than one
person at a time is unlikely. As operative technology becomes increasingly sophisticated,
learning the use of the new devices before actual operations on patients is mandatory. To
augment and possibly replace the classic cadaver model, virtual simulated environments
are being produced (28). The principles have been developed and applied by the aviation
industry in the use of flight simulators for pilot training and for operational readiness.
Flight simulators are relatively sophisticated devices, but the requirements for surgical
simulation are even more complex. The number of operational options possible at each
step is far greater in surgery, and the potential for subsequent cascading effects grows
geometrically. A few simulators exist that can be used for basic procedures such as
endotracheal intubation, placement of an intravenous needle, or bronchoscopy. The
greater the complexity of the procedure, the more interactivity is needed between the
virtual environment and the student. Visual feedback is needed, but feedback also can be
tactile and auditory. The surgeon senses tissue by feel and is aware of the surrounding
operating room through sound clues. Immersion, or the feeling of being within and able
to manipulate an environment, recreates the surgical experience and necessitates a high
degree of computing power.
The first requirement is visual depiction of the surgical field. It must be anatomically
correct and be able to respond to surgical manipulation. It emulates tissue characteristics
in response to manipulation, such as bleeding. The field also is turned in three dimensions
so that various approaches can be considered or the effects of the operation can be
viewed from different perspectives.
The other sense that must be brought to play is touch. Tactile simulation can replicate the
texture of an object, such as smooth or rough. The surgeon needs the sense of force
feedback or proprioception. This is the resistance produced by an object being
manipulated and transferred to the user by mechanical means so that the sensation of
holding the object is produced (28). This can be accomplished with haptic mechanical
sensors that impart both tactile and force feedback responses. The sensation can be
transmitted through instruments or gloves. Interaction with the simulator is rapid and can
be altered as the circumstances warrant by means of speech and gesture commands.
Voice recognition and action in the simulation elicit various responses throughout the
procedure. The simulator is a teaching device that offers suggestions during the training
period to best accomplish the task.
One of the most complex simulators has been developed for training in ESS (29). The
risks of ESS can be grave, and training is critical for optimum outcome. A cadaver
dissection can be performed only once per side, and improvement in skills necessitates
real patient experience. The ESS simulator derives its data from a cadaveric model at the
National Institute of Medicine and was modified with proprietary software. (The ESS
simulator was made through collaboration of the Madigan Army Medical Center,
Lockheed Martin Tactical Defense Systems, Ohio State Supercomputer Center, Ohio
State School of Medicine, University of Washington School of Medicine Human
Interface Technology Lab, Immersion Corporation, and the Uniformed Services
University of the Health Sciences) (Fig. 94.10). The intranasal and sinus structures are
labeled as needed for identification. The procedures are of varying degrees of complexity
and respond to user interaction. An endoscopic view is seen on a monitor, and the CT
data set is available. Many surgical instruments are available and can be changed through
the voice recognition system. The haptic feedback emulates knives, needles, forceps,
scissors, microdbriders, and other instruments. Tissue effects such as blanching with
vasoconstrictor injection or bleeding that clouds the endoscope offer a true surgical field.
Progress of the trainees can be monitored with a number of criteria, such as time to
complete the task and number of misses (errors) made. The ESS simulator is being
evaluated for effectiveness as a training tool for otolaryngology residents and attending
surgeons. It also can be used to evaluate the dexterity of medical students who want to
pursue a surgical career.

FIGURE 94.10. A: Endoscopic sinus surgery simulator
(Lockheed-Martin). B: Close-up of endoscopic sinus
surgery simulator shows nasal instrumentation and
monitor.



Anatomy of the temporal bone and middle ear is taught by means of dissection and is a
standard task in resident training. A virtual temporal bone allows dissection from many
approaches and allows repetition of dissection or a surgical procedure as often as is
wanted. Three dimensions can be displayed to supplement the trainee's conceptual
renditions (30). Simulators are being developed as effective teaching tools for a number
of otolayngologic procedures (Fig. 94.11).

FIGURE 94.11. A: Temporal bone. B: Temporal bone
removed and inner structures magnified.



DIGITAL CAMERA APPLICATIONS
The use of computers and digital equipment has become common among physicians in
the work environment. The focus on technology as a means to improve productivity,
document patient encounters, and communicate with other physicians has been
increasing. The ability to rapidly and successfully document patient abnormalities and
physical findings has important implications for communicating with referring physicians
and maximizing use of electronic medical records. All these issues are addressed well
with a digital camera. This type of imaging, used to document the patient's condition,
surgical results, and physical and radiographic findings will certainly become an integral
part of the daily practice of medicine.
Photographic documentation of medical procedures and patient findings has become the
standard of care in modern medicine. The 35-mm camera has served this function well
over the past several decades. As technologic advances have occurred in computer
science, the digital camera has become an alternative to 35-mm photography in
documenting procedures and patient findings. Digital cameras have a conventional
camera body and lens but record images on a charge coupled device, a silicon chip
composed of individual elements, pixels, that react to light in much the same way as do
film grains in a conventional 35-mm camera. The chip records voltage, which is
converted to bits within a computer in the camera. Resolution of a digital camera is
related to the density of the pixels on the charge coupled device. The minimum resolution
needed to recognize the details of a patient image is 768 512 pixels (31); however, this
resolution still greatly limits detail and is not acceptable for most applications. It is
certainly not publication quality. The resolution of typical slide film is 4,096 2,736
pixels per frame (31). This degree of density is expensive in a digital camera, and the
resultant file size, nearly 34 MB, is too large for most applications (31). Therefore a
compromise must be reached between a workable file size and an acceptable level of
detail. This is left to the individual user to decide on the basis of the application. Images
needed for simple documentation and inclusion in an electronic record can be much
smaller in size and resolution than an image needed for publication.
The current generation of digital cameras has more features and density than do earlier
devices. As with any computer equipment, technologic advances continue at a dizzying
rate, and smaller, less expensive cameras with greater image density continue to be
developed. Many midrange digital cameras have an image resolution of 1,800 1,200
with a density of 2.3 megapixels. Images can be stored on memory cards, which are
initially placed in the camera and then are removed and protected from re-recording, or
on a hard drive, CD-ROM, or extended memory disk such as a ZIP disk. Images
transferred to a personal computer for labeling and storage can be saved in a variety of
formats. JPEG files (Joint Photographic Expert Group) are used most commonly because
they can be imported easily into word-processing, presentation, or photo manipulation
programs. Digital cameras are similar in size to conventional 35-mm point-and-shoot
cameras and are smaller and lighter than 35-mm single lens reflex (SLR) cameras.
Direct comparison of 35-mm photography and digital photography has shown conflicting
results (32,33,34,35 and 36), although most authors using newer digital cameras have
found them to be equivalent in photographic quality to 35-mm cameras. Kokoska et al.
(32) studied use of a digital camera in the care of patients undergoing cosmetic facial
surgery. The investigators compared images obtained with a Nikon 35-mm SLR camera
with those obtained with three digital cameras, ranging in resolution from 0.8 to 1.5
megapixels per image. The Nikon SLR camera was found to be superior in overall
quality, color, and contrast. It was found equivalent, in the investigators' rating system, to
some of the digital cameras in focus, distortion, resolution, and shadow. The investigators
concluded that the choice of camera, digital or 35 mm, depends on the planned use,
because each device has distinct benefits and limitations. It was surprising, however, that
the earlier model digital cameras, with their limited resolution, scored as well as they did.
Wilcox and Grimwood (36) compared digital and 35-mm images in dermatology and
found 35-mm images better for diagnosing dermatologic lesions. However, the difference
was not statistically significant, and the digital camera used was very limited by today's
standards. Other authors (33,34 and 35) found the benefits of digital images outweighed
the limitations. Frank et al. (34), who studied use of digital images for radiology
publication, found digital images equivalent to or better than conventional 35-mm images
for radiographic reproduction.
Digital cameras have been used in many medical fields. Dermatologists (31,36,37) have
evaluated use of this technique for remote diagnosis, teaching catalogs, and
photodocumentation. Use of these cameras in the surgical setting has been advocated in
neurosurgery for the planning of epilepsy surgery for children (38), in urology (39), in
vascular surgery (40), and in plastic surgery (41). It has also found a niche for autopsy
because of the ease of recording, immediacy of results, cost-effectiveness, and ability to
easily catalog images and information (33). Examples of digital photography in a head
and neck practice are shown in Fig. 94.12, Fig. 94.13, Fig. 94.14, Fig. 94.15 and Fig.
94.16. These figures show the quality of these images for office photography, intraoral
photography, radiographic imaging, and intraoperative photography.

FIGURE 94.12. Office photograph shows a patient with
a large arteriovascular malformation of the tongue.



FIGURE 94.13. Axial computed tomographic scan of the
neck (soft-tissue window with contrast enhancement)
shows T3 squamous cell carcinoma of the tonsil.



FIGURE 94.14. Axial computed tomographic scan of the
sinuses (bone window) shows expansile changes from a
left frontoethmoid mucocele.



FIGURE 94.15. Intraoral photograph shows T1
squamous cell carcinoma of the right retromolar trigone.



FIGURE 94.16. A:. Intraoperative photograph shows
total laryngectomy with bilateral selective neck
dissections (levels II, III, and IV) for recurrent glottic-
subglottic carcinoma after failed partial laryngectomy and
radiation therapy 7 years earlier. B: Close-up shows left
cricoid cartilage of patient depicted in A. Tumor is
present on both superficial and deep surfaces of inner
lamina of the left cricoid cartilage (above wooden stick).
C: Close-up shows hyoepiglottic ligament from patient depicted in A and B. Detail of
mucosa and submucosal vasculature is evident. D: Operative defect of patient depicted in
A, B, and C shows color contrast between structures, including jugular vein, carotid
artery, mucosal surface, deep tongue base, and submucosal surface of vallecular mucosa.



Digital cameras, particularly those with high resolution capabilities, provide excellent
images for use in clinical medicine. The benefits of this photographic technique are listed
in Table 94.1. Such imaging technology is critical to the development of telemedicine
and computer-based medical services using the Internet. Buntic et al. (42) used digital
imaging to transfer photographs and radiographic images of trauma patients across the
Internet to evaluate patients for extremity replantation. They found this to be a valuable
aid in the appropriate analysis and referral of these patients. The images provide rapid
and accurate assessment of the patient. In a study of telemedicine in vascular surgery,
Wirthlin et al. (40) evaluated 38 extremity wounds in 24 patients and compared wound
assessment by a remote surgeon with that performed by an on-site surgeon. The investi-
gators found good concordance between the two surgeons' findings. Similar diagnoses
were rendered and treatment recommendations were made. Studies such as this are
critical to the thoughtful development of remote medicine and consultation by means of
the Internet. Dieu and Donahoe (41) used digital photography and the Internet to
photograph complex wounds in the emergency department, transmit the images to the
supervising plastic surgeon, and receive instructions in emergency management of the
wound.

TABLE 94.1. BENEFITS OF DIGITAL
PHOTOGRAPHY AND IMAGING



Although there are important benefits to digital photography in its current state, there are
some limitations as well. A conventional digital camera, with its point-and-shoot
configuration, that is, small camera body with integral lens and off-center integral flash,
has difficulty photographing the oropharynx and posterior oral cavity because of
inadequate lighting and difficulty focusing. Although such limitations can be overcome in
the operating room with additional focused lighting, that is not practical in the office.
This issue can be addressed with a ring flash and manual settings; however, these options
are not available for most digital cameras that cost less than $1,000. The standard f-stop
and aperture settings with which most photographers are familiar in 35-mm photography
do not apply in digital photography. As with any new technology, there is a learning
period to allow facility with the device. Most of the current cameras also do not allow
direct connection with endoscopes or microscope eye-pieces as C-mount devices do for
35mm cameras. This can be overcome by adding a digital capture device to the
endoscopic video cart. This device allows acquisition of direct digital images.
Alternatively, the camera can be put in series with the video cart equipment and capture
an image directly to the camera, if it allows streaming incoming video with capture
(many allow incoming video but do not allow capture). It also is possible to produce
conventional photographic output and scan the picture into the computer for cataloging.
The benefits of this technology are enormous. Many experts believe that the benefits of
digital imaging clearly outweigh the limitations and that technologic advances will
minimize the limitations. This method of photography should allow seamless integration
of patient images, clinical, radiographic, pathologic, or otherwise, into the medical
record. Manipulation of the images with lighting, filters, or other processing techniques
may allow diagnostic advances, such as the ability to differentiate between benign and
malignant surface lesions. The decreasing cost of this technology, with its improved
images and enhanced capabilities, should allow rapid dissemination of this photographic
technique.
ADVANCES IN ENDOSCOPY
Diagnostic Virtual Endoscopy
Operative endoscopy has long been the mainstay of evaluation of lesions of the upper
aerodigestive tract beyond the scope of standard office evaluation. The additional risks of
such an approach include anesthetic complications, transgression of mucosal surfaces,
and airway problems such as obstruction or laryngospasm. An extension of imaging and
three-dimensional bony reconstruction with CT is reconstruction and presentation of
other surfaces in a three-dimensional structure. Moharir et al. (43) performed soft-tissue,
three-dimensional reconstruction of complex head and neck cancers by combining CT
and MRI data. The investigators showed that on these images tumor, nerve, brain tissue,
and other important structures can be highlighted in contrasting colors for evaluation of
the interfaces between these tissues. This technique allows a multiplanar, interactive
approach to the lesion and provides useful and novel information regarding the tumor-
tissue interface. Applications such as this will allow considerable improvement in
operative planning and access. Other authors (44,45) used virtual en-doscopy of the head
and neck and showed the potential benefit while citing some of the limitations. An
example of such an image is presented in Fig. 94.17. Additional enhancements are
needed to allow complete use of this technology.

FIGURE 94.17. Virtual endoscopic radiograph of
tracheobronchial tree shows tracheal stenosis.



Luminal surfaces, such as in the tracheobronchial tree and the esophagus, have been
prime candidates for this approach. The advantages to this type of imaging are accurate
depiction of structural changes due to luminal abnormalities, such as tracheal stenosis,
bronchial narrowing caused by an extrinsic or intrinsic lesion, laryngeal and subglottic
relations, and inner ear structural changes (46). All these can be seen without the patient's
undergoing anesthesia and an invasive procedure. In the case of virtual imaging of the
inner ear, details and structural issues can be shown that cannot be seen in a living
person. Sufficient scanning speed and resolution have even allowed virtual endoluminal
endoscopy of the abdominal aorta and its branches (47). The ability to image other soft-
tissue structures deep to the luminal surface and to evaluate their three-dimensional
structure in a multiplanar manner has benefits that are yet to be realized. The inclusion of
such data into surgical simulators may allow surgeons to perform an operation on a
simulator before performing it on a patient. The benefits of such a practice session are
enormous.
The main disadvantages of virtual endoscopy are a lack of surface characteristics, notably
color, that have important implications for diagnosis and treatment, and poor imaging of
flat or submucosal lesions, if these lesions are seen at all. Additional limitations are
present when two mucosal surfaces are in apposition during imaging, such as the
pyriform sinus, base of the tongue, epiglottis, vallecula, or soft palate, or when bulky
tumors appose on multiple surfaces (44). Poor imaging also is produced if there is much
pooling of secretions or if there are motion artifacts.
A discussion of individual applications of virtual endoscopy begins with the most studied
of the techniques, virtual bronchoscopy. Virtual bronchoscopy has been well described in
the literature (48,49,50,51,52,53 and 54), comparisons between virtual and endoscopic
bronchoscopy being most prevalent. Virtual bronchoscopy has been used most often to
assess airway patency and stenosis and has advantages over bronchoscopy in evaluating
the lumen distal to stenosis, an area often not visualized with flexible bronchoscopy.
Rapp-Bernhardt et al. (48) found virtual bronchoscopy to be equivalent to fiberoptic
bronchoscopy, axial CT, and multiplanar CT reconstruction in the localization and
grading of tracheobronchial stenosis. They also found it superior to other radiographic
techniques in estimating length of stenosis. In an earlier study, these same authors (50)
compared virtual bronchoscopy with conventional bronchoscopy in the care of patients
with tracheobronchial infiltration of esophageal carcinoma. They found similar results for
virtual endoscopy and bronchoscopy with respect to location, grading, and measurement
of length of stenosis. The pitfalls include poor visualization because of mucous plugs and
technical aspects of obtaining images. Neumann et al. (49) found that variations in the
accuracy of virtual bronchoscopy depended on the CT protocol used and on the
experience of the observer. Virtual bronchoscopy has been used to guide needle
aspiration biopsy of hilar and mediastinal lymph nodes (53). It also has been used in the
care of children to evaluate esophageal atresia and tracheal stenosis with 100% sensitivity
and specificity compared with the standard, endoscopic bronchoscopy (54).
Further applications of virtual endoscopy are present within the head and neck. Fried et
al. (55) studied this technique to evaluate the larynx. They performed virtual
laryngoscopy on several patients with a variety of laryngeal diseases. The novelty of the
study was the melding of CT and MRI data to allow inclusion of soft-tissue structures as
well as the luminal surface to provide an interactive experience to view the depth of the
pathologic condition and its relation to surrounding structures. Burke et al. (56) evaluated
the subglottic and upper tracheal airways by means of virtual endoscopy for 30 adult and
pediatric patients with stridor or airway obstruction. The investigators found that virtual
endoscopy was not as sensitive as actual endoscopy in the evaluation of dynamic airway
obstruction. They found the techniques equivalent in cases of fixed obstruction.
Despite the accessibility of the nose and paranasal sinuses to office evaluation, virtual
endoscopy has been used in rhinology. Gilani et al. (57) wrote that this evaluation allows
visualization of intranasal structures, such as the frontal duct and recess, from unusual
angles not possible with conventional endoscopy and provides unique insight into the
anatomic features before surgery . Along the same lines of thinking, Nakasato et al. (58)
used virtual nasal endoscopy to determine safe surgical entrance points for the intranasal
drainage of paranasal sinus mucoceles. Virtual nasal and paranasal sinus endoscopy has
been performed preoperatively on 45 patients before ESS (59). A high degree of
correlation was found between virtual endoscopic and surgical findings. Studies such as
this point to advances possible with this technology that may allow surgeons to perform
electronic surgery on a virtual endoscopic image.
Virtual endoscopy has been used to examine otologic structures. The procedures ranged
from otoscopy, which is similar to the examination performed in the office with
visualization of middle ear structures (30), to advanced medial to lateral visualization of
the structures of the inner ear (46). Seeman et al. (60) evaluated middle ear structures by
means of virtual middle-ear and inner-ear endoscopy for 12 subjects, both healthy
persons and patients who had undergone a surgical procedure. The investigators found
that this technique may aid in planning of and assessment after middle-ear surgery. Some
transparent technology also allows the surgeon to peal off layers of the image, as if
surgically removing them, or making some structures translucent to allow deeper
structure identification. Although virtual endoscopy of the structures of the inner ear may
have few surgical implications, it has great promise for teaching and for evaluating the
structural abnormalities of congenital anomalies of the ear.
Surgical Adjuvants
Contact Endoscopy
Contact endoscopy entails application of tissue dye and microendoscopic examination
with an instrument such as a microcolpohysteroscope. Contact endoscopy was first used
in otolaryngology in 1995, by Andrea et al. (61,62), who examined the larynx. In this
technique, the surface epithelium is stained with methylene blue, after which a
microcolpohysteroscope is applied to the surface. According to epithelial characteristics,
such as regularity, mitosis, nuclear dimension and color, cytoplasmic inclusions,
koilocytes, and others, specific epithelial patterns are identified for several mucosal
abnormalities (62). This technique allowed cellular distinction between chronic
laryngitis, keratosis, dysplasia, papilloma, and malignancy among 92 patients who
participated in a study (61). This evaluation may be important for tailoring the type of
phonosurgery performed at initial excision of a lesion if appropriate pathologic
characteristics are present. These findings were repeated by Carriero et al. (63) in a
separate study of this technique. Carriero et al. found cytologic abnormalities present at
contact endoscopy that were consistent with the histologic findings among all patients.
Richtsmeier et al. (64) used contact endoscopy to examine normal visceral tissue within
the neck. They found discrete contact endoscopy patterns in some of the human viscera,
such as thyroid and parathyroid. Richtsmeier et al. hypothesized that the technique may
become important for intraoperative identification of organs and structures. This
technique has not yet been given a niche in otolaryngology. It may be best used to
examine the oral mucosa to differentiate normal, dysplastic, and neoplastic mucosa.
Endoscopy in Otology
Endoscopes traditionally have been used to examine the nose, paranasal sinuses, and
larynx within the field of otolaryngology. Since the early 1990s, however, several
investigators have used endoscopic techniques in otology and evaluation of the ear. Poe
et al. (65) in 1992 first published their experience with transtympanic endoscopic
evaluation of the middle ear cleft. They found the technique valuable for office
evaluation of middle-ear disease and for surgical planning. This technique has been
advocated to evaluate perilymphatic fistulae because it avoids the artifacts present during
surgical exploration of the middle ear (66). Transtympanic endoscopy also has been used
as a surgical adjuvant to evaluate the attic, sinus tympani, facial recess, hypotympanum,
and other aspects of the middle ear with angled endoscopes (67,68). An endoscope also
can be used during neurootologic procedures (69,70 and 71). Wackym et al. (69) found
use of endoscopes improved visualization during posterior fossa vestibular neurectomy,
allowed more complete neurectomy, minimized cerebellar retraction, and decreased the
risk of cerebrospinal fluid leak. Similar benefits have been found when endoscopes are
used for surgical management of acoustic neuroma (70,71). One group of investigators
(71) found a statistically significant decrease in the rate of postoperative cerebrospinal
fistula, from 18% to 0%, after routine use of an endoscope to identify patent temporal
bone air cells that could not be identified with conventional microscopic techniques. It
seems evident that use of endoscopes in the setting of otologic and neurootologic
procedures has clear advantages over conventional methods. This procedure will no
doubt become common practice.
Endoscopic Neck Surgery
As gynecologists and general surgeons have developed more advanced and complex
endoscopic abdominal procedures and instruments, surgeons have sought other anatomic
sites to use these minimally invasive techniques. An attractive site for such surgery has
been the neck because of the cosmetic issues associated with cervical incisions and the
tissue characteristics of some cervical structures. Techniques are being developed to
address parathyroid and thyroid surgery. Endoscopic thyroidectomy has been performed
successfully by several groups (72,73,74 and 75), who have advocated many different
techniques. All techniques leave a limited neck wound or in some cases no neck wound
(73). Endoscopic thyroidectomy should be viewed as investigational because no single
large series has been reported. There are also limitations in regard to size of the lesion,
such as a large multinodular goiter, the pathologic diagnosis, and the need for central
compartment lymphadenectomy. Carreno et al. (76) showed the possible complications of
this technique in an animal model. The investigators found carbon dioxide gas dissection
into the chest, gas embolism, carotid occlusion, and limited visualization with risk to
adjacent structures. Many of the cosmetic issues are addressed by the practice of many
modern thyroid surgeons of us-ing extremely small incisions for an open technique. This
approach minimizes the scar while maximizing access.
The one area in which endoscopic neck surgery may make the most sense is exploration
of the parathyroid glands. The small structures excised, precise visualization of the
endoscope, and critical surrounding anatomic structures make this area ideal. This
procedure usually has been performed unilaterally to evaluate for primary
hyperparathyroidism when results of a sestamibi scan have been positive (77). Some
authors (78), however, have shown a higher complication rate among patients who
undergo endoscopic exploration of the parathyroid glands and a high rate of conversion
to an open technique. Those authors (78) advocate careful patient selection and have
guarded optimism about this technique. Clinical trials are needed before routine use of
this technique, even for unilateral adenoma.

HIGHLIGHTS
Radiology is becoming closely integrated into the operative
experience.
Preoperative three-dimensional reconstruction can assist the
surgeon in the planning and execution of procedures.
Image-guided surgery for biopsy, ESS, and other applications,
has been found useful in increasing surgical accuracy and
safety.
Surgical simulation can be used to train physicians at many
levels of experience. It also can reproduce pathologic
conditions before an actual procedure to familiarize the surgeon
with potential intraoperative concerns.
Digital imaging is affordable and of sufficient quality for
routine use in the clinical and academic setting.
Digital imaging provides the visual substrate for improved
communication between physicians and pa-tients and between
physicians and colleagues through conventional interaction and
telemedicine.
Intraoperative use of endoscopy continues to expand to provide
accurate and detailed inspection of minute areas of the
operative field, particularly when they are not well visualized
with conventional techniques. This technique is expected to
bring about advances in minimally invasive surgery.
Virtual endoscopy is expected to become a critical component
in the evaluation of disease. It allows analysis of the interface
between lesions and normal tissue and allows visualization
distal to obstructing lesions.
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57. Gilani S, Norbash AM, Ringl H, et al. Virtual endoscopy of the paranasal sinuses using
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58. Nakasato T, Katoh K, Ehara S, et al. Virtual CT endoscopy in determining safe surgical entry
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

95 ALTERNATIVE MEDICINE IN OTOLARYNGOLOGY
Head & Neck SurgeryOtolaryngology
95




ALTERNATIVE MEDICINE IN
OTOLARYNGOLOGY
BENJAMIN F. ASHER

B.F. Asher: Departments of Surgery and Pediatrics, Dartmouth Medical School, Dartmouth Hitchcock
Clinic, Berlin, Vermont.


Naturopathy
Acupuncture and Oriental Medicine
Otitis Media
Homeopathy
Osteopathic Medicine
Ayurvedic Medicine
Chiropractic
Body Work
Psychoneuroimmunology
Conclusion
Chapter References
The burgeoning interest in nontraditional or unconventional therapies among Americans
was uncovered by Eisenberg et al. (1) in their now landmark survey. The survey of 1,539
adults showed that one of every three respondents had used an unconventional therapy.
Seventy-five percent of these persons had not informed their personal physicians of their
practice. It was estimated from the survey that 13.7 billion dollars is spent annually on
these treatments. In a follow-up study, Eisenberg et al. (2) found that use of alternative
therapies had increased from 33.8% in 1990 to 42.1% in 1997. Estimated expenditures
increased 45.2% between 1990 and 1997. The total expenditure for 2000 is estimated to
be 21.2 billion dollars. In another survey, Astin (3) found that patients choose alternative
medicine not because of a dissatisfaction with conventional medicine but because these
alternatives are more congruent with their philosophical orientation toward health and
life.
Alternative therapies are provided by various licensed and unlicensed providers
naturopaths, chiropractors, acupuncturists, Oriental physicians, homeopaths, osteopaths,
massage therapists, mind-body practitioners, such as hypnotherapists, re-birthers, and
guided-imagery therapists, and holistic allopathic physicians. The surge of interest in this
area is monitored in the general press, where almost daily articles appear on the subject,
at book stores, where literally hundreds of new titles appear, and on the Internet, where a
multiplicity of websites are devoted to the subject. Most medical schools have introduced
courses on alternative medicine. A number of peer-reviewed journals are devoted to
alternative and complementary medicine. Some states now require insurance companies
to cover alternative therapies. The National Institutes of Health has established a National
Center for Complementary and Alternative Medicine to promote research in the field.
As the use of alternative therapies has become more accepted in the mainstream of
conventional medicine, a need has arisen to redefine what is considered alternative.
Attempts at redefinition have led to the terms complementary, holistic, nontraditional,
and integrative. Each term has a different meaning, but none is completely satisfactory.
Alternative implies that the therapy is used as a substitute for conventional practices. This
is often not the case; thus the concept of complementary medicine arose. Complementary
implies that the therapy works in conjunction with a conventional approach, but that the
complementary approach does not stand on its own. Nontraditional as a term is
relativistic in nature. Approaches considered nontraditional in modern U.S. culture, such
as acupuncture and Oriental medicine, are considered traditional in much of the world.
The term holistic refers to a style of medical practice in which the totality of the patient is
considered; it is a complete physical, mental, emotional, and spiritual perspective. The
holistic approach is well illustrated in many current cancer treatment programs in which a
patient participates in therapy groups or has massage or prayer added to the course of
physical treatment. Holism, however, does not refer to the underlying theory of
pathophysiology. Allopathic physicians may be quite holistic, and an alternative
practitioner may not be holistic at all. The most recent term to emerge integrative
medicine is an attempt to blend all of the other concepts. It assumes that practitioners
have a basic understanding of all of the various conventional and unconventional
therapies available and in what situations they may enhance each other. The term implies
that all options are considered from a holistic perspective, from which an individual
course of treatment is derived. Therapies may or may not complement each other. A
specific unconventional approach or a specific conventional approach may be the best
and only therapy needed. This term may be becoming the preferred term because it is the
most inclusive. However, for the purposes of this chapter and to avoid confusion, the
term alternative therapies is used.
The purpose of this chapter is to give the otolaryngologisthead and neck surgeon an
overview of the most prevalent alternative medical models and to present some of the
alternative therapies for common otolaryngologic problems. The scientific evidence
supporting these treatment modalities is evolving. Some therapies have been shown to be
efficacious, some merit further research, some may be ineffective but benign, and some
are clearly dangerous. This chapter describes the underlying philosophies of various
alternative or complementary systems in medicine. If research has been conducted,
results are presented. These therapies are being discussed, not necessarily advocated. It is
apparent that people use alternative therapies regardless of scientific validity. Because so
many patients are seeking this type of care and so few are informing their physicians, it is
incumbent on physicians to be informed about alternative medicine. Having a basic
understanding of the few most commonly used alternative medical practices fosters
physician-patient communication.
NATUROPATHY
Naturopathic medicine has its roots in ancient medical practices. As a form of medicine it
was brought to the United States in the late nineteenth century by Benedict Lust, who was
schooled in the practice of hydrotherapy. Lust founded the first college of naturopathy in
New York City. Naturopaths today are an eclectic group of practitioners. The scope of
practice includes homeopathy, manipulation, ayurveda, nutritional medicine, naturopathic
obstetrics, botanical medicine, and minor surgery. Naturopathic education is 4 years at
one of three colleges of naturopathy in the United States. Naturopaths receive a doctor of
naturopathy degree. They are formally licensed in at least 11 states, but many naturopaths
practice in states without formal licensure. Fundamental to the practice of naturopathy is
the concept of vitalism. The philosophy of vitalism is based on the concept that life is too
well organized to be explained simply as a complex assemblage of physical and chemical
reactions. The whole is greater than the sum of the parts, and the body has the ability to
heal itself. At a conference in the late 1980s, six unifying principles of naturopathy were
established, they are (a) vis medicatrix naturae (the healing power of nature), (b) treat the
whole person, (c) primum no nocere (first do no harm), (d) tolle causam (identify and
treat the cause), (e) prevention is the best cure, (f) docere (doctor as teacher). Because the
practice of naturopathic medicine remains eclectic, naturopathic treatments fall into
several categoriesnutrition, diet, and botanicals. Some naturopaths also use
homeopathic remedies, but homeopathy is discussed herein as a separate subject.
According to results of a study by Nsouli et al. (4), immunoglobulin Emediated food
allergy has assumed an important role in the naturopathic management of otitis media,
both acute and chronic. Although the study had many design weaknesses, the results are
cited often in the naturopathic literature. In this study, 104 nonrandomized, unselected
patients, some of whom had recurrent acute otitis and some of whom had chronic otitis
media with effusion, were evaluated with skin prick testing, radioallergosorbent testing,
and food challenge. Seventy-eight percent of the patients had specific food allergies.
With a 16-week elimination diet, 86% of the middle ear effusions were alleviated.
Seventy of the patients received a food challenge without double blinding, and 94% of
the effusions recurred.
Pizzorno and Murray (5) in the Textbook on Naturopathic Medicine suggest the following
therapy for acute otitis media: -carotene, vitamin C, zinc picolinate, bioflavonoids, and
evening primrose oil and thymus extract. They also recommend the following botanicals:
Echinacea angustifolia, Hydrastis canadensis (goldenseal) and Glycyrrhiza glabra
(licorice). Echinacea angustifolia, goldenseal, and thymus extract are compounds thought
to stimulate the immune system and improve immune function (6). Eardrops of mullein
flower and garlic in an olive oil base often are prescribed as an analgesic and
antiinflammatory medication.
Sinusitis is understood by many naturopaths as a condition caused by overproduction of
mucus. Mucus is thought to be overproduced when waste material is not being properly
eliminated by the intestines, kidneys, and skin. Treatment addresses excess production of
mucus with diet, botanicals, and inhalation therapy. Types of dietary management include
elimination of mucogenic food such as wheat and dairy products as well as adding foods
that are cleansing such as hot lemon drinks, garlic, onions, and horseradish. A botanical
prescription may include H. canadensis (goldenseal). Other herbs to manage sinusitis
include Solidago virgaurea, Sambucus nigra, echinacea, and Baptisia tinctoria.
Nutritional supplements for acute sinusitis include vitamin C, bioflavonoids, vitamin A,
-carotene, zinc lozenges, and thymus extract. Steam inhalation treatment also is
prescribed. This can include compounds such as benzoin, eucalyptus, peppermint,
lavender, and pine oil. Saline nasal irrigation also is used. One frequently prescribed
method for nasal irrigation entails use of a neti pot. This is a small porcelain pot with a
narrow spout. Several other plastic devices for nasal irrigation are now on the market.
Shea butter placed on the upper lip often is used as a nasal decongestant. This butter is
made from the seed of the shea butter tree, Butyrospermum parkii, which is native to
Africa. In one study, investigators found shea butter to be effective as a nasal
decongestant (7).
Naturopathic management of tonsillitis also entails attempts to improve immune function.
Goldenseal and echinacea are given for immune support. Garlic is given for its purported
antimicrobial properties. Vitamin C, bioflavonoids, vitamin A, -carotene, zinc lozenges,
and thymus extract may be given as nutritional supplements.
Gingko biloba has been studied as therapy for tinnitus, and the results have been
conflicting. Initial results of a study in France were promising, but two follow-up trials
did not replicate the results. The mechanism of action of gingko is not completely known,
but the main effects appear to be related to its properties as an antioxidant and
vasodilitant and an ability to decrease blood viscosity (8,9 and 10).
Echinacea is perhaps one of the most popular herbs used for the prevention of upper
respiratory infections. Three species of echinacea are commonly usedEchinacea
purpurea, E. pallida, and E. angustifolia; each is chemically different. The German
Commission E Monographs contained positive assessments of E. purpurea herb and E.
pallida root. There were insuffi-cient data on other preparations. A randomized double-
blind, placebo-controlled trial to compare the efficacy of E. angustifolia with that of E.
purpurea in relation to a placebo in the prevention of upper respiratory tract infections
showed no statistically significant difference between placebo and herb (11).
Various nutritional supplements have been shown to affect wound healing. Vitamin E
diminishes platelet adhesion. In the laboratory, vitamin E has been shown to diminish
wound healing. Vitamin A has a positive effect on wound healing and reverses the
immune depression associated with injury, sepsis, and surgery. Bromelain, derived from
the stem of the pineapple plant, has documented antiinflammatory activity and can be
helpful in resorption of hematoma (12).
ACUPUNCTURE AND ORIENTAL MEDICINE
Traditional Chinese medicine is thousands of years old and is rooted in Taoist
philosophy. Fundamental to Chinese medicine are the concepts of yin and yang and qi
(pronounced chee). Yin represents water, quiet, substance, and night. Yang represents
fire, noise, function, and day. The two are polar opposites, and there is a balance between
these two forces in the body. Qi can be translated in many different ways, but it is
fundamentally the vital energy throughout the body and the universe. Chinese medicine
stresses the interaction between the persons's qi and that of the natural environment. It is
important to recognize that Chinese medicine considers the person a part of the universe,
and this relation influences a person's health. The language of Chinese medicine reflects
this philosophy. Thus the five elements (wood, fire, earth, metal, and water) and other
environmental factors, such as wind, heat, and humidity, are integral factors considered in
health and disease. When there is an imbalance between yin and yang, the body can be
invaded, and diseases can arise. Qi flows through specific channels in the body called
meridians. Altering the flow of qi can reestablish balance in the body, and health can be
returned.
An acupuncturist assesses a person's health through medical history and examination of
the pulse and of the tongue. Traditional Chinese medicine identifies 28 pulse qualities,
such as wiry, choppy, slippery, or deep floating. The tongue is examined for color, shape,
and coating. With this information, the state of balance of the body can be understood
and therapy planned. Needles may be placed in the appropriate acupuncture points to
reestablish balance. Many practitioners also use traditional Chinese herbs; moxibustion,
an intense heat treatment focused on specific points; and massage treatments, including
cupping, in which a device that resembles a suction cup is used.
Practitioners of acupuncture and Oriental medicine receive training in various ways.
Physicians with a doctor of medicine or doctor of osteopathy degree can become certified
acupuncturists through a program at the University of California at Los Angeles.
Practitioners who are not physicians can receive training at one of the many schools of
acupuncture and Oriental medicine throughout the United States. Some states license
acupuncturists, some states require certification, and some states do not regulate
acupuncture practice at all.
A difficulty in bridging conventional Western medicine with traditional Chinese
medicine is the completely different concepts of the origins of disease. The following is
the traditional Chinese concept of the pathophysiologic mechanism of otitis media.
Otitis Media
Otitis media is classified as acute serous, acute suppurative, and chronic suppurative.
Acute serous otitis media is caused by external pathogenic wind in the form of infection
that spreads to the ear or cold wind blowing on the ear; a damp pathogenic factor due to
damp weather or too much swimming; or heat that affects the gallbladder channels. The
treatment principle is to expel the wind and release the exterior, clear the heat, and
resolve the toxicity (13). Acute suppurative otitis media is caused by invasion of external
pathogenic wind-heat toxin, often originating in the respiratory tract, which rises up to
the ear. The treatment principle is to clear the heat, decrease the dampness, resolve the
toxicity, reduce the swelling, and alleviate the pain (14). Chronic suppurative otitis media
occurs when acute otitis media is not relieved or is partially relieved or when the body is
severely weakened by overwork or chronic disease. The treatment principle is to move
the qi in the ear, disperse the blockage, invigorate the blood, and expel the pathogenic
factor (14).
Specific therapies for otitis media include acupuncture, administration of herbs that
increase digestive fire, reduction of phlegm-forming foods (dairy products and sugar),
and massage around the ears to improve drainage (tui na). A National Institutes of Health
Consensus Development Panel on Acupuncture identified several areas with convincing
evidence to support acupuncture therapy. The areas include control of postoperative pain,
chemotherapy-induced nausea and vomiting, and postoperative dental pain (15). Several
trials of acupuncture to manage tinnitus have been conducted, and the results have been
conflicting. In a systematic and critical review of all studies of acupuncture for tinnitus,
the investigators found that acupuncture is ineffective for this problem (16).
In an unpublished review of a series of cases, I found that five patients with severe
chronic sinusitis and nasal polyposis documented with computed tomography had no
improvement when treated with traditional Chinese medicine and examined with
posttreatment computed tomography. T'ai chi, a form of Chinese exercise, has been found
effective in improving the conditions of patients with mild balance disturbance (17).
HOMEOPATHY
Homeopathy was developed by Samuel Hahnemann, a German physician in the late
1700s, after he became frustrated with the failings of then current medical practices.
Homeopathy is based on two fundamental principlesthe law of similars and the law of
infinitesimals. The law of similars is that like cures like (similia similibus urantur). A
substance that causes symptoms in a healthy person helps cure those same symptoms in a
sick person. Hahnemann developed this theory while experimenting with quinine. He
found that when he took it in high doses, quinine produced symptoms quite similar to
those of malaria. Hahnemann hypothesized that giving a remedy that mimicked
symptoms enhanced the body's ability to fight the same symptom. The law of
infinitesimals is that dilution of a remedy increases its potency. Homeopathic remedies
undergo serial dilution and are vigorously shaken or succussed between dilutions.
Remedies can be diluted from a ratio of 1 to 10 to 1 to 1 billion. The highest dilution that
contains no actual molecules of the remedy is the most potent (18).
There are two basic approaches in classic homeopathythe complex or clinical approach
and the isopathic approach. In the clinical approach, homeopathic remedies are applied to
conventional allopathic disease classifications. The isopathic approach incorporates
disease causes and biologic processes into the homeopathic method. In this approach,
homeopathic remedies are prepared from diseased tissue or secretions and given to the
patient. An example is administration of a remedy prepared from infected skin to a
patient with a similar skin infection. Homeopathy is used as therapy for both acute and
chronic conditions. For an acute condition such as a sore throat, the history and
symptoms reviewed may be entirely problem centered. For a chronic condition, such as
chronic sinusitis, a homeopath catalogs an extremely detailed history that includes
localized symptoms and general information, such as tolerance of temperature, quality of
sleep, appetite, sexual desire, overall review of systems, level of energy, emotional
limitations, and the quality of interpersonal relationships.
A homeopathic practitioner matches symptoms to a specific remedy. Remedies are
classified in the homeopathic Materia Medica according to a detailed description of the
symptoms that they provoke in high dosages. Homeopathic remedies are regulated by the
U.S. Food and Drug Administration. Homeopathic practitioners usually are medical
doctors, doctors of osteopathy, naturopathic physicians, or chiropractors. In some states
homeopaths are certified homeopathic physicians with no doctoral degree. Homeopathic
practice is regulated in many states, but in some states it is not. Homeopathy is far more
accepted in Europe. According to a survey conducted by the National Center for
Homeopathy, 40% of Dutch, 39% of French, 20% of German, and as many as 37% of
British physicians use homeopathy. Research has shown positive treatment associations
in homeopathic therapy for seasonal allergic rhinitis (19) and influenza (20). Results of a
yet to be published, randomized, double-blind, placebo-controlled pilot study showed that
homeopathy was no more effective than placebo in the management of acute otitis media.
Another randomized, double-blind, controlled study showed that a proprietary
homeopathic remedy (Vertigoheel) was as effective as betahistine hydrochloride in the
treatment of patients with vertigo of various origins (21).
OSTEOPATHIC MEDICINE
Osteopathic medicine is no longer considered alternative; most osteopathic physicians
now practice allopathic medicine. The primary difference between allopathic and
osteopathic training is that osteopathic students receive additional training in
manipulative medicine. This is why osteopaths and chiropractors often have been
wrapped together. Only a small percentage of osteopathic physicians limit their practices
to osteopathic manipulative medicine, and many practice no manipulation at all.
Osteopathy was founded in 1872 by Andrew Taylor Still as an alternative to the crude
allopathic practices of the middle to late 1800s. Still was an allopathic physician
disaffected by conventional medicine after the death of his wife and children to spinal
meningitis. He stopped practicing medicine after the Civil War and spent time observing
the relation between structure and function in the body. From his observations, Still
developed osteopathic medicine. He believed that the action of muscles, ligaments, joint
mechanics, joint surfaces, and joint motion all influenced the cardiovascular and nervous
systems. Still postulated a general theory that lesions, or disturbances of particular
regions of the spinal column, resulted in disease (somatic dysfunction) in the organs fed
by the nerve impulses coming from those areas (22).
In essence the original concept of osteopathy held that
1. With any human body there exists a constant tendency towards health. If this
capacity is recognized, and if treatment takes its relevance into account, then
prevention and normalization of disease processes is enhanced. 2. The structure of
the body is reciprocally related to its function. By this it is meant that any change
in structure will alter some aspect of function and converse any alteration, and
function will result in structural changes. 3. Health is the primary area to be
studied in attempting to understand disease. 4. The musculoskeletal system, which
incorporates the bones, ligaments, muscles, fascia, etc., forms a structure which,
when disordered, may affect the function of other parts and systems of the body.
This might be the result of irritation or abnormal response of the nerve and/or
blood supply to these other organs or parts. 5. The body is subject to mechanical
disorder and is therefore capable of mechanical correction. (22)
Osteopathic manipulative practice is quite varied. Many techniques entail attempts to
restore normal physiologic motion to areas in which motion is restricted or dysfunctional.
Some techniques include high-velocity manipulative techniques, muscle-energy
techniques, massage, and cranial osteopathy. An offshoot of cranial osteopathy practiced
by nonphysicians is Upledger Craniosacral Therapy. This modality has become popular
with massage therapists and physical therapists. Of all of the osteopathic manipulative
therapies, cranial osteopathy is perhaps the most controversial and therefore the most
alternative. Cranial manipulation was developed by William Garner Sutherland, a student
of Still. Sutherland observed the internal bevel of the suture between the squama of the
temporal bone and the greater wing of the sphenoid bone and the external bevel of the
suture between the temporal bone and the inferior border of the parietal bone. He
postulated that this type of joint was designed for motion. He further postulated that five
types of intrinsic motion are associated with the cranium, central nervous system, and
sacrum: (a) articular mobility of the cranial bony mechanism, (b) articular mobility of the
sacrum between the ilia, (c) inherent mobility of the central nervous system, (d)
fluctuation of the cerebrospinal fluid, and (e) inherent motion of the dural membranes.
Sutherland called this the primary respiratory mechanism. He believed that restrictions in
the mobility of this mechanism would cause various diseases. Sutherland experimented
on himself with mechanical devices to produce and correct distortions of his own
cranium. He applied these principles to his patients. The inherent motion of the cranial
bones and the primary respiratory mechanism have been well documented in osteopathic
sources (23).
Practitioners of cranial osteopathy postulate that restrictions in the primary respiratory
mechanism can cause conditions such as otitis media and sinusitis. Otitis media is
believed to be the result of restriction of the normal physiologic motion of the temporal
bones that impedes eustachian tube function. Sinusitis is thought to be caused in part by
restriction of motion of the bones of the midface that impedes drainage of the sinuses.
Therapy is directed at reestablishing normal physiologic motion to these areas through
gentle manipulative techniques (23). No studies have been performed to document the
efficacy of osteopathic cranial manipulation for otitis media or for sinusitis.
AYURVEDIC MEDICINE
Ayurvedic medicine was developed in ancient India. The word is derived from two
Sanskrit roots, ayur, which means life and veda which means knowledge. Ayurvedic
physicians were the first to perform plastic and reconstructive surgery. The forehead flap
was initially described in the Sushruta Samhita, the ayurvedic textbook of surgery (circa
800 BCE).
An ayurvedic physician, a vaidya, considers disease an imbalance in a person's
constitution (prakriti). The psychosomatic temperament of the person, his or her
constitution, is determined by a particular combination of three qualities (doshas)vata,
pitta, and kapha. There are seven combinations in all. Ayurvedic physicians believe that
in health the doshas are balanced. Disease occurs when there is an imbalance. Ayurvedic
diagnosis is an attempt to ascertain the types of imbalances present. Therapy is directed at
rebalancing the doshas. Ayurvedic therapy includes cleansing, palliation, rejuvenation,
and mental hygiene. A few techniques include diet, herbs, purgatives, enemas, massage,
and meditation (24).
Ayurvedic physicians in India receive formal medical training at an ayurvedic medical
school. Practitioners of ayurvedic medicine in the United States who have not trained in
India are taught at one of a few institutes of ayurvedic medicine in the United States.
Ayurvedic training also is available at colleges of naturopathy. There is no specific
licensure or certification for ayurvedic practitioners.
Although no studies have validated the efficacy of ayurvedic therapies for otitis media
and sinusitis, the following are treatment regimens that often are prescribed. Otitis media
often is seen as an imbalance (increase) of pitta and kapha. Treatment is an attempt to
reduce kapha. Garlic oil in the ear canal may be used. The herb Berberis aritata taken
internally and as an oil in the ear canal also can be given. Massage of the neck to improve
lymphatic drainage can be prescribed.
Sinusitis also is a pitta-kapha imbalance. Therapy for acute sinusitis includes nasal lavage
with a neti pot. The herbs B. aritata and neem can be taken internally or included in the
lavage. Heat packs and hot pepper gargles can be used. Evaluation for chronic sinusitis is
much more complex. Factors such as poor digestion and poor liver function are taken into
account. Treatment supports the immune system with the herb amla and improves
digestion and reduces kapha with ginger and an ayurvedic herbal preparation, triphal.
Herbal enemas can be used.
CHIROPRACTIC
Chiropractic medicine was developed by Daniel David Palmer in 1895. Palmer postulated
that the vitality of a person is sustained by the normal functioning of the central nervous
system. The function of the central nervous system is impaired by subluxations
(misalignments) of the spinal column. He came to this conclusion after he realigned a
bump on the back of his deaf janitor's neck and restored his hearing (25). The American
Chiropractic Association defines chiropractic as that science and art which utilizes the
inherent recuperative powers of the body and the relationship between the
musculoskeletal structures of the body, particularly the spinal column and the nervous
system, in the restoration and the maintenance of health(26). Chiropractors manually
adjust spinal vertebrae to reestablish motion in the vertebral column. They believe that
this reestablishes normal functioning of the nervous system, which is the basis for a
person's health and well-being. There are philosophical differences among practitioners
of chiropractic. These philosophical differences are reflected in the main chiropractic
societies. The American Chiropractic Association is the largest society and reflects the
views of most chiropractors. This philosophy of chiropractic is that chiropractors can
choose not only to practice spinal manipulation but also to incorporate treatments such as
counseling about nutrition, lifestyle, body mechanics, stress management, acupressure,
soft-tissue manipulation, and homeopathy. The conservative philosophy of Palmer is
carried forth by the Federation of Straight Chiropractic Organizations. Members of this
organization limit practice to adjustments of the vertebral column. They believe in the
innate intelligence of the spinal column and firmly believe that chiropractic
adjustments are not to be mixed with other types of therapy (26).
Chiropractic education requires 4 years of study. At least 2 years of college with specific
basic science prerequisites are required before admission. Chiropractic students, like
medical students, receive training in basic sciences such as anatomy, neuroscience,
biochemistry, microbiology, and pathology, but they receive little training in
pharmacology, general medicine, and surgery. The focus of clinical training is in
chiropractic technique and philosophy, chiropractic diagnosis, neuromusculoskeletal
diagnosis, and radiology. All chiropractic students are required to serve at least 900 clinic
hours in a college-operated clinic. Passage of the National Board of Chiropractors
examination is required for licensure in most states.
Chiropractors are licensed in all states to adjust the spine and related structures. There are
differences among states in types of adjunctive care permitted by chiropractors. For
example, some states permit only spinal adjustments and do not allow dispensing of
nutritional supplements or the ordering of blood tests. Other states allow chiropractors to
administer nonprescription proprietary drugs, order diagnostic tests, and perform
massage. Most research on chiropractic has focused on the management of
musculoskeletal problems. Chiropractic manipulation has been found to be effective for
neck pain, back pain, and headaches (27). No important studies have been performed to
evaluate chiropractic for acute otitis media.
BODY WORK
Body work is a term to describe a variety of therapeutic modalities, such as massage and
body awareness, that incorporate hands-on healing. Although research has been
conducted to relate body work to the conditions discussed in this chapter, body work is
perhaps the most popular adjunctive therapy. It is being discussed herein to give
otolaryngologists a familiarity with the most commonly used terms to facilitate
communication with patients.
Most hands-on therapists are licensed as massage practitioners. Although most states
have licensure requirements that include 500 to 1,500 hours of training, some states allow
almost anyone to call himself or herself a massage therapist. The education of a massage
therapist includes anatomy and physiology courses, but the 1 to 2 year course of study
has no educational prerequisites. The American Massage Therapy Association has a
voluntary national certification program that requires passing written, oral, and practical
examinations. Members also have continuing education requirements. Al-though these
practitioners do not consider themselves qualified to diagnose diseases or design a course
of medical treatment, many believe that the techniques can enhance or assist the healing
process.
Massage techniques vary from the vigorous kneading of muscles and deep tissue to
gentle laying-on of hands in which practitioners claim subtle energy flows from their
hands to the patient. Specific styles include Swedish massage, rolfing, Hellerwork,
shiatsu, acupressure, lomi lomi, reiki, reflexology, polarity, and trigger point therapy.
Many massage techniques, such as Trager work and Aston patterning incorporate body
awareness. These techniques are attempts to retrain the way a person moves and
maintains the body in space. Some approaches focus on body awareness and movement
alone without hands-on techniques. Many of these movement approaches such as the
Feldenkreis method, the Alexander technique, Pilates, and gyrotonics have roots in
dance. Because practitioners of body awareness and movement reeducation do not
practice hands-on therapy, no licensure is required. However, these instructors often are
certified by the organization through which they teach.
PSYCHONEUROIMMUNOLOGY
The field of mind-body medicine, or psychoneuroimmunology, investigates the
interrelations between the mind and the body and disease. Research in this field is
growing, especially in the areas of stress reduction and oncology. Stress reduction
through various techniques has been shown to be efficacious in the management of
numerous problems, including asthma, anxiety disorders, hypertension, heart disease, and
depression (28).
CONCLUSION
Patients coming to an otolaryngologic practice may be using any number of alternative
therapies. It is important that otolaryngologists become familiar with these therapies.
When practitioners are informed about therapies that many patients undertake,
communication is enhanced. This communication is the foundation of a solid physician-
patient relationship.

HIGHLIGHTS
Patients use alternative medicine because it is more congruent
with their philosophical orientation toward health and life.
Seventy-five percent of patients who use alternative medicine
do not inform their physicians.
Acupuncture is not effective for tinnitus, but t'ai chi, a form of
Chinese exercise, is effective for mild balance disturbances.
Homeopathy is not effective for acute otitis media, but the
proprietary homeopathic remedy Vertigoheel is effective for
vertigo.
No studies have established the efficacy of chiropractic or
osteopathic manipulation in the management of otitis media.
Stress reduction is known to be efficacious in the management
of a number of common medical problems.
Asking patients about their use of alternative medicine and
withholding negative judgments improves physician-patient
communication.
More research is needed in the field of alternative medicine.
CHAPTER REFERENCES
1. Eisenberg DM, Kessler RC, Foster C, et al. Unconventional medicine in the United States. N Engl
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2. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative medicine use in the United States,
19901997: results of a follow-up national survey. JAMA 1998;282:15691575.
3. Astin JA. Why patients use alternative medicine? JAMA 1998;279:15481553.
4. Nsouli TM, Nsouli SM, Linde, RE, et al. Role of food allergies in otitis media. Ann Allergy
1994;73:215218.
5. Pizzorno J, Murray M. A textbook of natural medicine. John Bastyr College Publications,
1989:292295.
6. Pizzorno J. Encyclopedia of natural medicine. Prima, 1990:507509.
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Butyrospermum parkii. Br J Clin Pharmacol 1979;7:495497.
8. Meyer B. A multicenter randomized, double-blind drug versus placebo study of ginkgo biloba
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1994;33:8592.
10. Wedel HV, Calero L, Walger M, et al. Soft laser/ginkgo therapy in chronic tinnitus. Adv
Otorhinolaryngol 1995;49:105108.
11. Melchart D, Walther E, Linde K, et al. Echinacea root extracts for the prevention of upper
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12. Petry JJ. Surgically significant nutritional supplements. Plast Reconstr Surg 1996;97:233240.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

96 UNDERSTANDING DATA AND INTERPRETING THE LITERATURE
Head & Neck SurgeryOtolaryngology
96




UNDERSTANDING DATA AND INTERPRETING
THE LITERATURE
RICHARD M. ROSENFELD

R.M. Rosenfeld: Department of Otolaryngology, State University of New York, Downstate Medical
Center; Department of Pediatric Otolaryngology, Long Island College Hospital, Brooklyn, New York.


How to Identify Articles Worth Reading
Five Basic Questions for Interpreting Data
Question 1: What Type of Study Produced the Data?
Question 2: What are the Results?
Question 3: Are the Results Valid Within the Study?
Question 4: Are the Results Valid Outside the Study?
Question 5: Are the Results Strong and Consistent?
Chapter References
It is a capital mistake to theorize before one has data, observed Sherlock Holmes.
Physicians are rarely guilty of this offense, because they are inundated with data from
clinical observations, journal articles, professional meetings, and government agencies.
Unfortunately, the theories that result often have little relevance to the data that produced
them. This is not unexpected, because physicians rarely devote the same efforts to
mastering data that they devote to mastering clinical skills. As a partial remedy, this
chapter offers a principle-centered approach to data analysis with emphasis on
interpreting the medical literature (1).
Nearly all data relevant to clinical care comes from articles in peer-reviewed medical
journals. Peer review, of course, refers to the mystical process whereby only high-quality
manuscripts are allegedly selected for publication. Manuscript assessment, however, like
even the most sophisticated diagnostic tests, has a certain sensitivity and specificity;
worthy articles may be unappreciated and unpublished or worthless ones may pass
undetected to the printing press (2). Peer reviewers may be biased, unqualified, or possess
widely discrepant opinions about a study. The bottom line? Caveat lector. Beware of
what you read even in excellent medical journals.
Of more concern to clinicians than the inadequacies of peer review, however, is that the
medical literature generally serves science rather than medical practice (3). Peer-
reviewed publications facilitate communication from scientist to scientist, not necessarily
from scientist to clinician. Most published studies are nondefinitive tests of hypotheses
and innovations, only a very small percentage of which may warrant routine clinical
application. Whereas the science may be sound, the idea has not progressed beyond the
laboratory or preliminary field studies. Definitive studies constituting true scientist to
clinician communication are rare in medical journals and must be identified through
critical appraisal.
HOW TO IDENTIFY ARTICLES WORTH READING
Articles worthy of in-depth analysis have enticing titles and abstracts and espouse
innovative, controversial, or clinically relevant ideas. The article generally appears as
original research in the main section of a peer-reviewed journal. Methods and results
sections, which represent the heart and soul of the article, are appropriately detailed and
long. Enough details are provided for readers to reproduce the study with a reasonable
chance of obtaining the same results. A quick review of the article in general discloses
many of the signs of grandeur listed in Table 96.1.

TABLE 96.1. SIGNS OF GRANDEUR AND
DECADENCE IN JOURNAL ARTICLES



Articles unworthy of in-depth analysis may have enticing titles and abstracts but do not
support the lofty claims and conclusions therein. The article may appear in a journal that
is not peer reviewed (throwaway journal) or in an industry-funded supplement to the
main section, which generally implies lower quality (4). Signs of decadence (Table 96.1)
are readily apparent in a perusal of the main sections of an article. The methods and
results sections are vague and sparse and are overshadowed by a verbose discussion
section that contains unsupported opinions and creative misinterpretations. Readers
should not waste any time analyzing an unworthy article unless the premise is so novel
and important that it overshadows obvious weaknesses.
It may be helpful to compare a journal article with a gourmet meal (5). Abstracts offer a
useful taste of study contents but are rarely sufficient to make a meal in themselves. A
well-crafted introduction provides a nourishing appetizer before the main course of the
article and may in itself make the reading worthwhile. The methods and results sections
constitute the main bill of fare, worthy of careful digestion and analysis. If the meal is
delicious (full of useful and high-quality evidence) one may want to sample the desert, or
discussion section. Discussion or comment sections are full of creative ingredients,
ranging from speculation to apologies, which can make them the most enjoyable part of
the meal, but hardly the most nourishing.
FIVE BASIC QUESTIONS FOR INTERPRETING DATA
As expert clinicians consider something abnormal until they examine it and prove
otherwise, a connoisseur of medical evidence considers a data set or a journal article
laden with flaws, distortions, and omissions until proven to the contrary. The five basic
questions in Table 96.2 are the key to this analytic process. Each question is discussed
with established principles of data analysis and literature interpretation (1,6).

TABLE 96.2. FIVE BASIC QUESTIONS FOR
INTERPRETING MEDICAL DATA



Question 1: What Type of Study Produced the Data?
Medical data arise from a research study, defined as an organized quest for new
knowledge, based on curiosity or perceived needs (7). Validity of the data is determined
in large part by the study design (specific procedures and methods) used by the
investigators to produce the data. Despite the befuddling array of study designs espoused
in the epidemiologic literature, a savvy data analyst need only address a few basic
considerations (Table 96.3). These relate to (a) the way in which the data were gathered,
(b) the degree of control the investigator had over study conditions, (c) whether a control
or comparison group was used, and (d) the direction of inquiry followed.

TABLE 96.3. EFFECT OF STUDY DESIGN ON
DATA INTERPRETATION



Data collected specifically for research (Table 96.3) are likely to be unbiased; they reflect
the true value of the attribute being measured. In contrast, data collected during routine
clinical care vary in quality depending on the specific method used (8). Experimental
studies such as randomized trials are likely to produce high-quality data because they are
performed under carefully controlled conditions. In observational studies, however, the
investigator is simply a bystander who records the natural course of health events during
clinical care. Although more reflective of real life than is a contrived experiment,
observational studies are more susceptible to bias. Comparing randomized trials with
outcomes studies highlights the difference between experimental and observational
research (Table 96.4).

TABLE 96.4. COMPARISON OF RANDOMIZED
CLINICAL TRIALS AND OUTCOMES STUDIES



The presence or absence of a control group has a profound influence on data
interpretation. An uncontrolled study, no matter how elegant, is purely descriptive (9).
Nonetheless, authors of case series often delight in unjustified musings on efficacy,
effectiveness, association, and causality. Without a control or comparison group, it often
is impossible to differentiate the natural course of disease from treatment effects. Placebo
effects, halo effects, and regression to the mean (Table 96.5) account for an average of
70% of good to excellent outcomes in uncontrolled studies (10). These effects underlie
the mysterious discipline of mind-body medicine, in which the placebo response is used
to promote health and recovery from illness (11).

TABLE 96.5. EXPLANATIONS FOR FAVORABLE
OUTCOMES IN TREATMENT STUDIES



When data are available from a comparison or control group, statistics can be used to test
hypotheses and measure associations. Causality also can be assessed when the study has a
time-span component, either retrospective or prospective (Table 96.3). Prospective
studies measure incidence (new events); retrospective studies measure prevalence
(existing events). Unlike time-span studies, cross-sectional inquiries (surveys, screening
programs, evaluations of diagnostic tests) measure association, not causality. Causality is
best assessed with randomized trials (experiments), because observational studies are
prone to innate distortions or biases caused by individual judgments and other selective
decisions (12).
A dangerous habit is to label all randomized trials high quality and all observational
studies, such as outcomes research, substandard. The best randomized trials make special
effort to ensure the adequacy of randomization, such as generating random numbers at
the pharmacy, to conceal treatment allocation from subjects and investigators (double-
blind method), and to analyze results according to intention to treat rather than including
only compliant patients (13). Randomization, however, cannot compensate for imprecise
selection criteria, poorly defined endpoints, inadequate follow-up data collection, or low
compliance with treatment. More meaningful data come from protocol-driven, controlled,
observational studies with unambiguous selection criteria, valid and reliable outcome
definitions, and uniform follow-up data collection.
Question 2: What Are the Results?
Descriptive Statistics
Describing results begins with definition of the measurement scale that best suits the
observations. Categorical (qualitative) observations fall into one or more categories and
include dichotomous, nominal, and ordinal scales (Table 96.6). Numerical (quantitative)
observations are measured on a continuous scale and are further classified according to
the underlying frequency distribution (plot of observed values versus the frequency of
each value). Numerical data with a symmetric (normal or gaussian) distribution are
evenly placed around a central crest or trough (bell-shaped curve). Numerical data with
an asymmetric distribution are skewed (shifted) to one side of the center or contain
unusually high or low outlier values.

TABLE 96.6. MEASUREMENT SCALES FOR
DESCRIBING AND ANALYZING DATA



In summaries of numerical data, the descriptive method varies according to the
underlying distribution. Numerical data with a symmetric distribution are best
summarized with the mean (Table 96.7) and standard deviation (SD), because 68% of the
observations fall within the mean 1 SD and 95% fall within the mean 2 SD. In
contrast, asymmetric numerical data are best summarized with the median, because even
a single outlier can strongly influence the mean. For example, if five patients are
observed after sinus surgery for 10, 12, 15, 16, and 48 months, the mean duration of
follow-up study is 20 months, but the median is only 15 months. In this case a single
outlier, 48 months, distorts the mean.

TABLE 96.7. DESCRIPTIVE STATISTICS



A special form of numerical data is called censored (Table 96.6). Data are censored when
(a) the study direction is prospective, (b) the outcome is time-related, and (c) some
subjects die, cannot be found for data collection, or have not yet had the outcome when
the study ends. Interpretation of censored data is called survival analysis, because of its
use in cancer studies where survival is the outcome of interest. Survival analysis allows
full use of censored observations by including them in the analysis up to the time the
censoring occurred. If censored observations instead are excluded from analysis (e.g.,
excluding all patients with less than 1 year of follow-up observation), the resulting
survival rates are biased, and sample size is reduced.
Nominal and dichotomous data (Table 96.6) are best described with ratios, proportions,
and rates. A ratio is the value obtained by means of dividing one quantity by another,
both of which are separate and distinct. In a study of tonsillitis treatment, for example, the
ratio of children with clinical resolution after 10 days to those who continue to have
symptoms may be 80/20 or 4:1. A proportion is a type of ratio in which the numerator is
included in the denominator. In the previously mentioned study, the proportion with
clinical resolution would be 80/100, or 0.80. An alternative is to multiply the proportion
by 100 and express it as a percentage (80%). Rates are similar to proportions except that
a multiplier is used (e.g., 1,000 or 100,000), and rates are computed over time. For
example, a study might report a rate of 110 physician office visits per 100 children per
year for upper respiratory infections.
Odds ratio, relative risk, and rate difference (Table 96.7) are useful for comparing two
groups of dichotomous data (14). In a study of otitis media and day care, investigators
may report an odds ratio of 1.6, indicating that a child who had otitis media was 1.6 times
more likely to have attended day care than a child with healthy ears. A relative risk of 1.6
means the incidence of otitis media was 1.6 times higher among children who attended
day care than among controls who did not. Because the relative risk is used to measure
incidence, it is used only in prospective (cohort) studies. When the frequency of events is
low, the relative risk and odds ratio are nearly equivalent. An odds ratio or relative risk
approaching unity (1.0) suggests no association between day care and otitis media.
The rate difference (also called risk reduction) can be expressed in absolute or relative
terms. Suppose that initial treatment failures for acute otitis media occur among 20% (A)
of children treated expectantly but among only 10% (B) of those who received
antibiotics. The absolute rate difference, A B, between groups is only 10%, but the
relative rate difference, (A B)/B, is 100%. As a measure of clinical importance, the
absolute rate difference is preferred because it is easier to interpret and takes into account
the baseline risk. Relative rate differences can be deceptive, especially when event rates
are low. A new antibiotic may be touted as causing 75% less gastric upset than an
established standard (relative rate difference), but the results are less impressive if the
rate decreases from 1.00% to 0.25% (absolute rate difference of only 0.75%).
Two groups of ordinal or numerical data are compared with a correlation coefficient
(Table 96.7). A coefficient (r) from 0 to .25 indicates little or no relation, from .26 to .50
a fair relation, from .51 to .75 a moderate to good relation, and greater than .75 a good to
excellent relation. A perfect linear relation yields a coefficient of 1.00. When one variable
varies directly with the other, the coefficient is positive; a negative coefficient implies an
inverse association. Sometimes the correlation coefficient is squared (R
2
) to form the
coefficient of determination, which is an estimate of the percentage of variability in one
measure predicted by the other. For example, if hearing levels have an excellent
correlation with duration of presence of middle ear fluid (r =.80), we can predict 64%
(R
2
) of the variability in hearing levels when we know the duration of presence of fluid.
A final aspect of descriptive statistics concerns reporting and interpretation of data from
diagnostic tests. Important concepts in reporting test characteristics are defined in Table
96.8. Sensitivity (true-positive rate) and specificity (true-negative rate) are fixed
properties of the test. Predictive values (positive and negative), however, vary according
to the baseline prevalence of the condition in the population where the test is applied.
Clinicians need to realize that likelihood ratios are being used with increasing frequency
in the medical literature (15,16).

TABLE 96.8. GLOSSARY OF STATISTICAL
TERMS ENCOUNTERED WITH DIAGNOSTIC
TESTS



Analytic Statistics
A single medical study with two or more groups almost always has a difference in group
outcomes. If we conclude that the groups are different, we may be mistaking chance
variation for treatment effects. If we conclude the groups are equivalent, we may have
missed a true difference (17). In statistical language (Table 96.9), we begin with a
testable hypothesis about the groups under study, such as gibberish levels in group A
differ from those in group B. Rather than keep it simple, we now invert this to form a null
hypothesis: gibberish levels in group A are equal to those in group B. Next we turn on a
computer, enter the gibberish levels for the subjects in both groups, choose an appropriate
statistical test, and wait for the omnipotent P value to emerge.

TABLE 96.9. GLOSSARY OF STATISTICAL
TERMS ENCOUNTERED WHEN TESTING
HYPOTHESES



The P value tells us the probability of making a type I errorrejecting a true null
hypothesis. In other words, if P = .10, we have a 10% chance of being wrong (false
positive) when we declare group A differs from group B. On the other hand, there is a
10% probability that the difference in gibberish levels can be explained by random
errorwe cannot be certain that uncertainty is not the cause. Uncertainty is present in all
data because of the inherent variability in biologic systems and our ability to assess them
in a reproducible way. Because we can never avoid uncertainty entirely in measurements
and observations, we estimate the probability (P value) that observed results are
consistent with unavoidable random variation or fluctuations.
In medicine, P < .05 is generally considered low enough to safely reject the null
hypothesis. When P > .05 we accept the null hypothesis of equivalent gibberish levels.
Nonetheless, we may be making a type II error by accepting a false null hypothesis (false
negative). For example, the gibberish levels may be different, but we conducted the study
with too few subjects to have a reasonable chance of overcoming the random fluctuations
that inevitably exist. Rather than state the probability of a type II error directly, we state it
indirectly by specifying power (Table 96.9). Power of 80% or greater is sufficient to be
reasonably certain that a true difference was not overlooked.
As an example of statistical inference, consider a prospective study to see whether ice
cream causes sneezing. Suppose that 80% of ice cream eaters (16/20) begin sneezing, but
only 50% of controls do so (10/20). If we infer that on the basis of these results for 40
specific patients, ice cream causes sneezing in general, what is the probability that we are
wrong (type I error)? Because P = .10 (Fisher exact test), there is a 10% chance of type I
error, so we are reluctant to associate ice cream with sneezing on the basis of the results
of this one study.
Intuition, however, tells us that a rate difference (absolute) of 30% seems meaningful, so
what is our chance of being wrong when concluding it is not? The probability of a type II
error is 48% (same as saying 52% power), which means we may indeed be wrong in
accepting the null hypothesis (18). Now suppose we repeat this study with twice as many
subjects, and 80% of ice cream eaters (32/40) start sneezing compared with 50% of
controls (20/40). The rate difference is still 30%, but now P = .01. Increasing the sample
size allows us to exclude chance variation as responsible for the observed findings.
Studies with negative findings are interpreted on the basis of statistical power, not P
value. There is a large difference between observing nothing in a study and proving that
nothing really happened (19). Most often not enough patients were studied to offer a
reasonable chance of not missing differences of up to 50% between groups (20).
Calculating sample size before beginning a study ensures that the planned number of
observations offer a reasonable chance (power) of obtaining a clear answer at the end
(21,22). The basic ingredients needed to calculate sample size include the smallest
difference that must be detected between the groups, the variability (standard deviation)
of this difference (if the measurement scale is numerical), the limit of tolerance of type I
error (typically 5% or 1%), and the limit of tolerance of type II error (typically 20% or
10%).
Statistical Significance versus Clinical Importance
The next logical question after Is there a difference? (statistical significance) is How big a
difference is there? (clinical importance). For example, in a clinical trial of therapy for
acute otitis media it was found that amoxicillin was superior to placebo as initial therapy
(P = .009) for nonsevere illness (23). Before endorsing amoxicillin on the basis of P
values alone, we need to look more closely at clinical importance. Initial treatment
success occurred among 96% of amoxicillin-treated children as opposed to 92% of
controls, yielding a 4% rate difference (96% 92%) favoring drug therapy. Is this finding
clinically important? Maybe, and maybe not.
Statistically significant results must be accompanied by a measure of effect size, which
reflects the magnitude of difference between groups (24). Otherwise, findings with
minimal clinical importance can become statistically significant when a large number of
subjects participate in a study. In the example, the 4% difference in success rates was
highly statistically significant because more than 1,000 episodes of otitis media were
analyzed. Large numbers provide high precision (repeatability), which in turn reduces the
likelihood of error. The final result is a hypnotically tiny P value, which may reflect a
clinical difference of trivial importance. A P value of .000001 with a rate difference of
5% is much less clinically relevant than a P value of .01 with an absolute rate difference
of 25%.
A useful measure of effect size is the number needed to be treated (NNT), which is
simply the reciprocal of the absolute rate difference (24). The NNT reflects the amount of
clinical effort that must be expended to achieve one additional treatment success. For
example, in the study cited, the NNT would be 25 (100% divided by 4%). An average of
25 children must be treated with amoxicillin to increase the rate of resolution of acute
otitis media by one child above what would occur with placebo treatment alone. Because
we cannot predict with certainty which 1 of the 25 children will benefit, we must treat all
25 patients.
What constitutes an important NNT magnitude depends on the severity of disease and the
side effects of treatment. An NNT of 25 may be extremely important in cancer therapy
but less exciting in management of acute otitis media. If the treatment has relatively
minor side effects, we may be willing to accept a higher NNT to justify routine use.
Antimicrobial therapy is considered optional for otitis media with effusion because
systematic reviews suggest a relatively modest NNT of 7.
Relative measures of effect size (relative risk, odds ratio, relative rate difference) provide
limited information in clinical trials because they do not reflect changes in baseline risk.
For example, a relative risk of 50% can mean that the treatment decreases the chance of
an unfavorable outcome from 4% to 2% or from 60% to 30%. Conversely, the absolute
rate difference and NNT reflect both the baseline risk and degree of relative risk
reduction. In the acute otitis media treatment trial (23), the decrease in treatment failures
owing to amoxicillin therapy was only 4% with rate difference but was an impressive
50% with relative risk. One always must scrutinize the amount of absolute change before
concluding that a relative change is clinically significant.
Question 3: Are the Results Valid Within the Study?
A measurement is valid if it is unbiased (free of systematic error) and reflects what it is
intended to measure. For example, an audiometer not properly calibrated can consistently
give readings that are off by 15 dB. The readings are precise (repeatable), but inaccurate
(biased). The reader needs to scrutinize the methods section of the article to be sure that
means for diagnosing disease, documenting therapy, and recording outcome are valid.
Was an algorithm or test of known sensitivity and specificity used in diagnosis? Were
measures used to document compliance with intended therapy? Are the outcome
measures clear and meaningful? Do surveys or questionnaires have psychometric
validity? If the answer to any of these questions is no, the validity of the results are in
question.
A study has internal validity when the design is appropriate for the area of investigation,
measurements are valid, and the data are analyzed with appropriate statistical tests. All
statistical tests have a common purposeto measure error. This purpose cannot be
fulfilled unless the correct test is used for the data being analyzed. To determine whether
the correct statistical test was used, the reader must check first whether the observations
come from independent or related samples; second, whether the purpose is to compare
groups or to associate an outcome with one or more predictor variables, and third, the
measurement scale of the variables. Table 96.10 and Table 96.11 can be used to find the
correct statistical test for valid analysis.

TABLE 96.10. STATISTICAL TESTS FOR
INDEPENDENT SAMPLES



TABLE 96.11. STATISTICAL TESTS FOR
RELATED (MATCHED, PAIRED, OR REPEATED)
SAMPLES



Two events are independent if the occurrence of one is in no way predictable from the
occurrence of the other. A common example of independent samples is two or more
parallel (concurrent) groups in a clinical trial or observational study. Related samples
include paired-organ studies, subjects matched by age and sex, and repeated measures on
the same subjects, such as before and after treatment. The situation sometimes is unclear,
as when ears, not patients, are the unit of analysis. Although each ear is a separate entity,
the two ears share common characteristics, such as eustachian tube function, nasopharynx
microflora, and host immune system. To analyze ears as independent samples, which
often occurs to inflate sample size, can bias results.
In the tests in Table 96.10 and Table 96.11 labeled parametric an underlying symmetric
distribution for the data, or a relatively large sample size (about 20 or more observations
per group), is assumed. If the data are sparse, asymmetric, or ordinal, a nonparametric
test must be used. Nonparametric tests rank the observations in order of magnitude and
compare the ranks not the measurements themselves. Nonparametric tests often are called
distribution-free tests because they can be applied to skewed or asymmetric data.
The following are brief examples to illustrate statistical test selection. Assume we are
comparing patient satisfaction for two different treatments using a five-point outcome
scale (poor, fair, good, very good, excellent). According to Table 96.10, the correct test
for two groups of independent ordinal data is the Mann-Whitney U test (Wilcoxon rank
sum is equivalent). If the investigators instead use a t test, results may be invalid. Now
suppose we want to compare hearing levels (numerical scale) before and after
stapedectomy for 50 patients. Using Table 96.11 (we are dealing with a matched sample),
we find a paired t test or Wilcoxon signed rank test can be used. Finally, if we want to
associate survival after tumor resection (a censored outcome) with several predictor
variables, such as age, type of surgery, comorbidity, TMN stage, we use proportional
hazards (Cox) regression (Table 96.10).
A fundamental assumption underlying all statistical tests is that the hypothesis under
study was fully developed before the data were examined in any way. When hypotheses
are formulated post hocafter even the briefest glance at the datathe basis for
probability statements is invalidated. Consider, for example, the Texas sharpshooter who
shoots an arrow at a barn wall then meticulously draws a bulls eye around it. When his
friends arrive, they applaud his incredible accuracy. We have no way of knowing at
which stage of the research process a hypothesis was developed. Data tortured
sufficiently eventually confess to something, and a post hoc hypothesis is born.
Question 4: Are the Results Valid Outside the Study?
Once it is determined that the investigator's conclusions correctly describe what happened
inside the study (question 3), the task is to determine whether the conclusions can be
applied (generalized) to the universe outside the study. Not all well-conducted, internally
valid studies have external validity (generalizability). This distinction is more than trivial,
because the most important question from the clinician's viewpoint is, Can I apply the
results of this study to the patients I see in my practice? For the answer to be yes, the
sampling method must be sound, the subjects must be representative of the target
population, and the sample size must be large enough for adequate precision.
Sampling a Population
When we interpret medical data, we ultimately seek to make inferences about a target
population on the basis of results in a smaller study sample (Table 96.12). Rarely is it
possible to study every subject with the condition of interest. Nor is it necessary
statistics allow us to generalize from the few to the many, provided that the few are
representative of the many. However, representative samples rarely arise from divine
providence. Review carefully the inclusion and exclusion criteria (check the methods
section) to be sure that the subjects studied are representative of those to whom you want
to apply the results. A study with vague subject selection criteria may yield fascinating
results, but we have no way of knowing to whom they apply.

TABLE 96.12. GLOSSARY OF STATISTICAL
TERMS RELATED TO SAMPLING AND
VALIDITY



Once it is determined that the target population and subject selection criteria are
meaningful, the next step is to assess how the study sample was selected. Investigators
typically have access to only a small subset of the target population because of
geographic, temporal, or demographic constraints. When investigators choose an even
smaller subset of this accessible population to study (Table 96.12), the method of
choosing (sampling method) affects their ability to make inferences about the original
target population. Unless an appropriate sampling method is used, the study sample may
differ systematically from the intended target population (selection bias).
The best sampling method is to randomly select members of the accessible population.
Bias is minimized because all subjects have a known (and equal) probability of selection.
Random sampling, however, rarely is feasible in most clinical research studies. A
consecutive or systematic sample offers a relatively good approximation. Consecutive
samples are common and include all subjects over a specified time or until a specified
sample size is reached. Systematic samples are obtained with a simple, systematic rule,
such as day of the week, date of birth, or first letter of last name. The worst sampling
method is choosing subjects on the basis of convenience or investigators' subjective
judgments about eligibility. Convenience (grab) sampling is assumed when no other
method is specified.
Random allocation of patients to treatment groups differs from random sampling of a
population. Randomization improves internal validity by reducing allocation bias (Table
96.5), but has no effect on external validity. Most randomized trials, however, have rigid
and restrictive subject selection criteria that tend to limit generalizability compared with
less restrictive outcomes-type studies (Table 96.4).
Precision and Confidence Intervals
Another component of external validity is precision, which reflects the degree of
variability in the observations. For example, if the hearing of 20 healthy volunteers is
measured on five different days, how likely is it that the the same mean result would be
obtained each time? Highly unlikely, because audiometry has a variable behavioral
component that depends on a subject's response to a stimulus and the examiner's
perception of that response. If the hearing of five groups of 20 healthy volunteers each is
measured, how likely is it that the same mean hearing level will be obtained in each
group? Again unlikely, because of variations between individuals. We would obtain a
range of similar results but rarely identical results in repetitive trials.
Variability (precision) must be dealt with in the interpretation of data, unless the results
are meant to apply only to the particular group of patients, animals, cell cultures, DNA
strands, and so on, in which the observations are initially made. Recognizing this
limitation, we call each of the descriptive measures in Table 96.7 a point estimate, which
is specific to the data that generate it. In medicine, however, we seek to pass from
observations to generalizations, from point estimates to estimates about other
populations. When this process occurs with calculated degrees of uncertainty, we call it
inference.
The following is a brief example of clinical inference. After administering echinacea to 5
patients with Mnire disease, you remark to a colleague that 4 had excellent relief.
She asks, How confident are you of your results?
Quite confident, you reply, there were 5 patients, 4 got better, and that's 80%.
Maybe I wasn't clear, she interjects, how confident are you that 80% of patients with
Mnire disease you see in the next few months respond favorably, or that 80% of similar
patients in my practice do well with echinacea? In other words, she continues, can you
infer anything about the real effect of echinacea from only 5 patients?
Hesitatingly you retort, I'm pretty confident about that number 80%, but maybe I'll have
to see a few more patients to be sure.
The real issue, of course, is that a sample of only 5 patients offers low precision
(repeatability). How likely is it that the same results would be found if 5 new patients
were studied? We can state with 95% confidence that 4 successes out of 5 in a single trial
is consistent with a range of results from 28% to 99% in future trials. This 95%
confidence interval can be calculated manually or with a statistical program (25,26 and
27) and tells us the range of results consistent with the observed data. If this trial were
repeated, we could obtain a success rate as low as 28%, not very encouraging compared
with the original point estimate of 80%. To make a metaphor to a mutual fund
prospectus, past performance is no guarantee of future results.
Precision can be increased (uncertainty can be decreased) by use of a more reproducible
measure, by means of increasing the number of observations (sample size), or by means
of decreasing the variability among the observations. The most common method is to
increase the sample size, because we rarely can reduce the variability inherent in the
subjects we study. If 50 patients (rather than 5) receive echinacea and 40 have symp-
tomatic relief, the 95% confidence interval for success narrows to 66% to 90%. The point
estimate, however, remains 80% (40/50). Although we are more confident in our results
after this larger trial, we cannot say anything about the efficacy of echinacea without an
untreated control group for comparison.
Realizing that uncertainty never can be avoided completely, we use statistics to estimate
precision. When data are described with the summary measures listed in Table 96.7, a
corresponding 95% confidence interval accompanies each point estimate (25). When
investigators report positive findings (P < .05), the lower limit of the interval is
scrutinized. If it is less than what you consider a clinically important effect size, precision
is inadequate. When investigators reports negative findings (P > .05), the upper limit of
the interval is checked. If it is consistent with a clinically important effect size, statistical
power is inadequate.
Question 5: Are the Results Strong and Consistent?
Results of a single studyno matter how elegant or seductiverarely are definitive.
Science is a cumulative process that requires a large body of consistent and reproducible
evidence before conclusions can be formed (28). In a review of an exciting study or data
set, the cumulative basis of science often is overshadowed by the seemingly irrefutable
evidence at handat least until a new study by different investigators in a different
environment adds a new twist.
The first step in assessing strength and consistency is to ask, Do the results make
sense? Findings that are biologically implausible, or that are inconsistent with those of
other known studies, often can be explained by hidden biases or design flaws that were
initially unsuspected. Improbable results can become statistically significant through
biased data collection, natural history, placebo effects, unidentified confounding
variables, or improper statistical analysis. Results of a study with design flaws or
improper statistical analysis have low internal validity and are reanalyzed or discarded.
At the next level of integration, we compare the study design that produced the current
data with the design of other studies the results of which have been published. The level
of evidence generally increase from uncontrolled observational studies (case reports, case
series) to controlled observational studies (cross-sectional, retrospective, prospective) to
controlled experiments (randomized trials) (29). For example, If results of several
randomized efficacy trials about the topic of interest have been published, an
uncontrolled study is unlikely to provide new insights. When a certain level of evidence
has been accumulated, causation can be inferred. Causation is an epidemiologic concept
based on the consistency, strength, specificity, and temporal relation of the association
between a factor and a particular disease or outcome (30).
The consistency of published studies also can be assessed on a quantitative level. A
simple table summarizing the current study and related studies is a good starting point,
but the studies may have widely discrepant subjects, methods, and outcomes. Systematic
reviews or metaanalyses are attempts to overcome the apple and orange problem with a
priori selection criteria to ensure consistency in the studies the results of which are
compared and statistically pooled (31,32). The bottom line typically includes a
summary measure of effect size, such as rate difference, a 95% confidence interval, and a
statistical test for heterogeneity among source articles. The best systematic reviews
include a comprehensive search for relevant articles and explicit criteria for rating
relevance and merit.

HIGHLIGHTS
The peer-reviewed medical literature generally serves science,
not medical practice; critical appraisal is needed to locate
clinically relevant and valid evidence.
Critical appraisal begins with the principles outlined in Table
96.1 and Table 96.2 with emphasis on the magnitude, clinical
relevance, and generalizability of the main results.
Study design has a profound effect on validity; answer the
questions in Table 96.3 before attempting to interpret or apply
results.
Improvement after therapy does not always equate with
improvement due to therapy; unless a study is controlled and
randomized, bias, chance, or natural history (Table 96.4) can
account for apparent efficacy of the intervention.
Statistical analysis involves describing results, selecting the
correct test on the basis of the nature of the variables and
questions being asked, and addressing clinical importance
(Table 96.6, Table 96.7, Table 96.8, Table 96.9, Table 96.10
and Table 96.11).
A properly performed and analyzed study has internal validity,
but the ability to generalize results beyond the study (external
validity) depends on sampling and subject selection criteria.
No amount of statistical wizardry can compensate for flawed
study design and biased outcome assessment; save your
intellectual energy for well-designed studies worthy of
interpretation.
CHAPTER REFERENCES
1. Rosenfeld RM. The seven habits of highly effective data users. Otolaryngol Head Neck Surg
1998;118:144158.
2. Kassirer JP, Campion EW. Peer review: crude and understudied, but indispensable. JAMA
1994;272:9697.
3. Haynes RB. Loose connections between peer-reviewed clinical journals and clinical practice. Ann
Intern Med 1990;113:724728.
4. Bero LA, Galbraith A, Rennie D. The publication of sponsored symposiums in medical journals.
N Engl J Med 1992;327:11351140.
5. Gehlbach SH. Interpreting the medical literature, 3rd ed. New York: McGraw-Hill, 1993.
6. Oxman AD, Sackett DL, Guyatt GH. Users' guides to the medical literature, I: how to get started.
JAMA 1993;270:20932097.
7. Last JM. A dictionary of epidemiology, 3rd ed. New York: Oxford University Press, 1995.
8. Sackett DL. Bias in analytic research. J Chronic Dis 1979;32:5163.
9. Moses LE. The series of consecutive cases as a device for assessing outcome of intervention. N
Engl J Med 1984;705710.
10. Turner JA, Deyo RA, Loeser JD, et al. The importance of placebo effects in pain treatment and
research. JAMA 1994;271:16091614.
11. Brody H, Brody D. The placebo response. New York: Cliff Street Books, 2000.
12. Feinstein AR. Fraud, distortion, delusion, and consensus: the problems of human and natural
deception in epidemiologic science. Am J Med 1988;84:475478.
13. Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias: dimensions of methodological
quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273:408
412.
14. Brown GW. 2 2 tables. Am J Dis Child 1985;139:410416.
15. Lang TA, Secic M. How to report statistics in medicine: annotated guidelines for authors, editors,
and reviewers. Philadelphia: American College of Physicians, 1997.
16. Dawson-Saunders B, Trapp RG. Basic and clinical biostatistics, 2nd ed. Norwalk, CT: Appleton
& Lange, 1994.
17. Brown GW. Errors, types I and II. Am J Dis Child 1983;137:58591.
18. Young MJ, Bresnitz EA, Strom BL. Sample size nomograms for interpreting negative clinical
studies. Ann Intern Med 1983;99:248251.
19. Schor S. Statistical proof in inconclusive negative trials. Arch Intern Med 1981;141:12631264.
20. Freiman JA, Chalmers TC, Smith H, et al. The importance of beta, the type II error, and sample
size in the design and interpretation of the randomized controlled trial: survey of two sets of
negative trials. In: Bailar JC, Mosteller F, eds. Medical uses of statistics, 2nd ed. Boston: NEJM
Books, 1992:357374.
21. Florey C. Sample size for beginners. BMJ 1993;306:11811184.
22. Brown GW. Sample size. Am J Dis Child 1988;142:12131215.
23. Kaleida PH, Casselbrant ML, Rockette HE, et al. Amoxicillin or myringotomy or both for acute
otitis media: results of a randomized clinical trial. Pediatrics 1991;87:466474.
24. Laupacis A, Sackett DL, Roberts RS. An assessment of clinically useful measures of the
consequences of treatment. N Engl J Med 1988;318:17281733.
25. Thomas DG, Gart JJ. A table of exact confidence limits for differences and ratios of two
proportions and their odds ratios. J Am Stat Assoc 1977;72:7376.
26. Gardner MJ, Altman DG. Confidence intervals rather than p values: estimation rather than
hypothesis testing. Br Med J 1980;292:746750.
27. Gustafson TL. TRUE EPISTAT Reference Manual. Richardson, TX: Epistat Services, 1994.
28. Light RJ, Pillemer DB. Summing up: the science of reviewing research. Cambridge, MA: Harvard
University Press, 1984.
29. Center for Evidence Based Medicine. Levels of evidence and grades of recommendation.
http://cebm.jr2.ox.ac.uk/docs/levels.html. Accessed December 1999.
30. Hill AB. The environment and disease: association or causation. Proc R Soc Med 1965;58:295
300.
31. Oxman AD, Cook DJ, Guyatt GH. Users' guides to the medical literature, VI: how to use an
overview. JAMA 1994;272:13671371.
32. Rosenfeld RM. How to systematically review the medical literature. Otolaryngol Head Neck Surg
1996;115:5363.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

97 THE BUSINESS OF MEDICINE AND PLANNING YOUR FUTURE
Head & Neck SurgeryOtolaryngology
97




THE BUSINESS OF MEDICINE AND PLANNING
YOUR FUTURE
LEE D. EISENBERG

L.D. Eisenberg: ENT and Allergy Associates, Englewood, New Jersey.


Financial Planning
Insurance Planning
Disability Income Insurance
Life Insurance
Fellowships
Lifestyle
Type of Practice and Availability
Contracting Issues
The Issues
Weighing the Issues
Starting the Practice
Advancing Your Practice
Affability
Communication
Availability
Bibliography
During residency you are concentrating on learning all aspects of otolaryngology. What
the future holds in the way of practice is often a distant thought. This chapter is intended
to help you begin the process of considering your future. Such a discussion is unusual for
a textbook of otolaryngology, but it is as important as learning to evaluate a patient for
illness. At the end is a resource list to further assist in planning for the years ahead. As
one progresses through residency, different issues become more important. Financial
planning and insurance needs are constant. Whether to undertake a fellowship, looking
for employment, and starting practice become concerns during the third and fourth years
of training but should be considered throughout.
FINANCIAL PLANNING
It is never too early to save for the future. Your needs change with time, but your
financial security does not come by chance. Most people need to save for three things
buying a house, education of children, and retirement. The types of investments you
make are an individual decision, and many sources of advice are available. Many
brokerage and other financial investments firms offer guidance and assist with planning,
both near and far term. Some of the questions you need to ask yourself are (a) How much
am I saving now? (b) If I continue to save as I have in the past, how much money will I
have in 10 years? (c) Am I satisfied with my current savings plan? (d) Will I save
systematically to reach my financial goals?
There are two ways to savespend first and save, or save first and spend what is left. Of
the two, the latter is the better choice. Table 97.1 emphasizes the advantage of saving at
an early age. It shows the monthly investments needed at different ages to accumulate
$1,000,000 by 65 years of age at an 8% compounded rate of return. The benefits of
starting to save early are evident. It seems that saving should be at the top of one's
priorities, but it requires discipline and planning.

TABLE 97.1. ADVANTAGE OF SAVING AT AN
EARLY AGE



INSURANCE PLANNING
As with financial planning, a number of resources are available to assist in determining
insurance needs. These can include insurance brokers, insurance agencies, and financial
planning firms. Although there are many insurance needs, the two that often require the
most attention are disability income insurance and life insurance.
Disability Income Insurance
You often have insurance for your life, health, car, and home, but you need to insure your
salary. Most disability policies do not start paying benefits until at least 30 days from the
date the insurer says you became unable to work. This means you have to be able to
support yourself for about 1 month. Savings play an important role. If you have a policy
that has a 90-day waiting period, which is often much less expensive, your savings need
to be that much greater. There are two basic disability coveragesany occupation and
own occupation. The former means that you are disabled only if you cannot work
anywhere. The latter gives you benefits if you cannot work in your specialty. Own-
occupation coverage is more expensive and, for physicians, not readily available, but it
may be worth the expense for peace of mind.
Life Insurance
There are two basic types of life insuranceterm and permanent or whole life. Which
form is more suitable for one's needs is and individual decision. The brokers and agencies
can offer advice, but they can be biased in their opinions and suggestions. Brokers and
agents make commissions on the policies they sell, and that may influence the
recommendations they make. As in medicine, a second opinion may be appropriate.
Determining the type and amount of life insurance one needs depends individual
circumstances. How much debt you have accumulated (house, educational, and other
loans), education for children, spousal and perhaps parent support have to be taken into
consideration.
With term insurance, you pay a specific premium for a certain amount of coverage for a
specified time. It may be up to 10 years. After that, the policy may or may not be
renewed at a higher rate. It is temporary protection.
Permanent or whole life insurance generally provides lifetime protection at a level
premium. When you are younger, it is more expensive than term premiums, but later the
premiums, because they are stable, become less than those of term policies. Whole-life
insurance also contains guaranteed cash and loan value. Whole-life insurance is a type of
savings in that the policyholder obtains benefit of the investment that can increase the
value of the policy over time (cash value).
FELLOWSHIPS
Do you need a fellowship? Before making this decision, you must consider how you
intend to practice in the future. If you plan to enter the academic environment, a
fellowship is almost essential. Full-time academic appointments are available directly
from residency, but these are not common. This depends on the needs of the institution
and where you trained.
In private practice, your desire to specialize in a specific area of otolaryngology can
influence your decision. The decision to specialize also depends your strengths and
weaknesses during training. Most otolaryngologists refine their practices over time and
become more proficient in specific areas, such as sinus surgery, and decide not to
perform other procedures, such as operations for head and neck cancer. Completing a
fellowship does not necessarily limit your practice, but it can influence your decision to
do so, such as specializing in neuro-otology or pediatrics. In many circumstances, the
decision to pursue fellowship training is to develop strength in a specific discipline that
eventually becomes most of your practice, such as facial plastic surgery.
Where you undertake your fellowship often depends on exactly what you consider your
needs to be and what is available. Your attending physicians, both full time and clinical,
are likely be your best source of information. As with all training, there are different
areas of strength and weaknesses within a fellowship. One may better fit your interests
and may be the deciding factor. As with residency applications, there may a matching
process. If are considering additional training, the beginning of your third year of
otolaryngology residency is the time to start the process.
LIFESTYLE
Where you live, the type of practice chosen, and family considerations are the most
important factors in ensuring your contentment in the future. Your earnings cannot
compensate for dissatisfaction or unhappiness. There are basically three types of
communities from which to chooserural, suburban, and urban. Which of these you
prefer often depends on your interests, family needs, type of practice, and job availability.
The latter may be the overriding factor, especially in the academic environment.
If you prefer small-town living, less congestion, and more outdoor recreation, living in a
large metropolitan area may not be appropriate. Your spouse may be offered a promotion,
which requires a move to a new locale, and this may become the deciding factor. The
desire to be close to family must also be taken into consideration. Where practice
opportunities exist also influences the decision. The first place you live need not be the
last. A change in environment or practice style may be important for everyone's
happiness.
TYPE OF PRACTICE AND AVAILABILITY
The practice options are solo versus group practice. Within otolaryngology, most
practices are smallone to three physicians. Although it can be difficult, solo practice is
still viable. Group practices vary widely. They can be single specialty or multispecialty
and can consist of two other physicians to more than 100. Each situation is unique and
affords different benefits. In solo practice, you are your own boss, but along with that
comes the responsibility of running a business. In the group setting, there may a loss of
autonomy, but there are less administrative responsibility and better financial security. As
you progress through residency, take the opportunity to observe and ask about the
different practice types. The community in which you choose to live often affects your
decision.
Finding the right opportunity available is the next step. Is there a need in the community?
There are a number of resources with this information. One of the best is the American
Academy of OtolaryngologyHead and Neck Surgery, Inc. (AAO-HNS), either the
bulletin or the website. At the annual meeting, job listings are located at the academy
booth. Otolaryngology journals often have job advertisements. Recruitment firms abound
and send you information on a regular basis, even after you have entered practice. Local
contacts in the community, either where you trained or where you live, can be of great
help. If you are interested in a specific community, you can ask other physicians whether
there is a need. Talking to pediatricians, internists, and family practitioners can give you
the best perspective. If you are entering the academic environment, usually after a
fellowship, your options may be limited by availability. The faculty at your place of
residency or fellowship may be the best resource. The AAO-HNS and the various
journals also have this information. You should begin to look for a practice at the end of
the third year of residency. If you are undertaking a fellowship, the search should begin
before you finish the fourth year. This gives you the opportunity to evaluate and
interview at a more relaxed pace.
Interviewing the practice is an important step. The physicians want to get to know you,
but you have the responsibility to know the practice. Whether you interview in person or
on the telephone, if the practice is far from where you live, you should obtain the
following information: an overall description of the practice, such as areas of
concentration, number of offices, presence of ancillary services, hospital affiliations, call
requirements, existence of an ambulatory surgery center, ages of other physicians in the
practice, salary, and benefits. If someone has recently left the practice, ask why and, if
possible, speak to that person. This preliminary discussion often determines whether you
or the practice wishes to pursue an agreement. One of the best opportunities for initial
contacts is at the annual meeting of the AAO-HNS. These meetings should be planned
well in advance and limited to two or three a day.
When you visit the practice for the first time, you bear the cost. If you are invited back
for more serious discussions, the practice may help defer some of the cost. Your spouse
should accompany you on the second visit. He or she may want to look at places to live,
schools, employment opportunities, and available activities. You may even contact a
realtor for assistance. Your family's happiness is imperative, and these other
considerations are important. At this visit, having dinner with the other physicians and
their spouses is beneficial. They may not be your best friends, but you should feel
comfortable with them. You can ask around the community, especially at the hospitals,
how the individual or group is perceived. This is a potentially lifelong commitment, and
you want and need all the information available to make an intelligent decision.
I always have one caveat about a practice: If one of the physician's spouses is an
employee, especially the office manager or in charge of billing and collections, seriously
consider looking elsewhere. As hard as they try, it is impossible for these persons to be
neutral. The office manager often acts as a buffer between the staff and the physicians.
You are an employee and as such may wish to have someone to talk to. If the office
manager is a spouse, you and the staff may be hesitant to do so. On the financial side, the
emphasis on collections can be influenced. This is not to say that this arrangement may
not work, but it often leads to difficulties within a practice and can eventually lead to its
dissolution.
CONTRACTING ISSUES
Hire an attorney. Not enough emphasis can be placed on this statement. The expense is
worth the long-term problems you avoid. The lawyer you hire should have expertise in
this area and often is from a large law firm. Ask for recommendations. Often an attending
physician has a suggestion. Where the attorney practices should not necessarily be the
deciding factor in choosing him or her. Comfort and knowledge are more important.
The Issues
The multitude of issues with regard to a contract include business terms, term of contract,
restrictive covenants, and ultimate purchase of interest in practice. There are also the
practical realities regarding the contract.
Business Terms
The business terms are (a) compensation, (b) bonus, (c) retirement plans, (d) insurance
malpractice, life, disability, health, (e) other fringe benefits, such as dues, board
examination, books and journals, meetings, automobile, and telephone, and (f)
indemnification.
Terms of Contract
The terms of contract are (a) length, (b) reasons for termination before expiration of
contract, and (c) what happens on expiration of the contract.
Restrictive Covenants
Issues about restrictive covenants include (a) enforceability, (b) length of time and
geographic limitations, and (c) coordination with termination provisions.
Ultimate Purchase of Interest in Practice
The issue in purchase of an interest in the practice include (a) pretax versus after-tax
dollars, (b) practice valuation, (c) stock purchase versus salary offset, (d) accounts
receivable, and (e) shareholders agreement.
Weighing the Issues
The number of issues involved in the contract can be overwhelming. There are, however,
the practical realities of joining a practice that seem right for you. Some components of
the contract are more important than otherssalary, bonus, termination, and
indemnification. Fringe benefits can be negotiable. Restrictive covenants often seem
onerous, but it is the practice that has to have them enforced. You, with the advice of
your attorney, must decide which issues are most important to you in deciding whether to
sign a given contract. In an academic setting, there is less leeway for negotiation, but
discussions include office hours, research support, teaching responsibilities, and other
departmental responsibilities.
STARTING THE PRACTICE
Before starting a new practice, whether solo or in an existing group, you need to do the
following: (a) obtain a state license, which can take 6 months; (b) obtain hospital
privileges, which you can do while waiting for you license; (c) place advertisements in
the Yellow Pages and obtain a listing in the white pages; the closing date for the
following year usually is around April or May; and (d) establish membership in health
maintenance organizations this is not an easy task, and you may need your license first.
The requirements for entering solo practice are greater than those of joining an
established practice. You need, at a minimum, financing, office space, employees, a
billing and collections system, letterhead stationery, telephones, office furniture, medical
equipment, and malpractice insurance. Your first employee is the most important and, if
possible, should be someone with experience. The local medical society may be of
invaluable help. The AAO-HNS, American Medical Association, and American College
of Surgeons all have material on setting up a practice. Once you begin, it is wise to find
an accountant experienced with medical practices. When you are joining a practice, you
may want to hire your own accountant to avoid possible conflicts.
ADVANCING YOUR PRACTICE
Once you have begun practice, you need to meet and greet. Sending announcements and
purchasing newspaper advertisements or using press releases is only the beginning. You
should eat lunch at the hospitals, walk through the emergency departments, sit in the
physician lounge, and introduce yourself to the nursing staff and intensive care
specialists. Visit the other offices of referring physicians. You may not always meet
them, but at least introduce yourself to the office manager and staff, who often make
suggestions to patients who need specialists. Bring some goodies and remember to
leave business cards. Make yourself available for speaking engagements, including grand
rounds, schools, senior citizen groups, and other organizations. Join the local medical
society and let them know you are available as a speaker. The following three attributes
can be invaluable to enhancing your practiceaffability, communication, and
availability.
Affability
Be nice. Seems trite, but it goes a long way. Be early. In the office this allows you to
review messages, answer telephone calls, discuss with the staff your schedule for the day,
and start seeing patients on time. If your are more than 20 minutes behind schedule at any
given time, offer an apology to the patient. This recognizes the fact that you have kept
them waiting and often defuses anger. When the delay is longer than 20 minutes, have the
office staff rearrange the schedule for that day. Offer the patients in the office the
opportunity to reschedule or return later that day. Patients with later appointments should
be called to make changes. If you are late to the office, the same scenario holds true.
Patients appreciate this thoughtfulness.
Always arrive in the operating room at least 15 minutes ahead of schedule. This lets the
staff know that you are prompt. More important, it allows you to discuss your needs for
the procedure before you begin. This is especially true when you are new or performing
an infrequent procedure at that hospital. When you are not performing the first procedure
of the day in the assigned room, call the hospital before you leave your office to learn the
status of your operation. This allows you to plan your day and again shows the surgical
staff that time is important to you.
Communication
Sending letters to referring physicians is an excellent method of teaching. The letters
should be concise. Some physicians prefer a cover letter with a copy of the typewritten
office notes. This keeps the referring physician informed about what you found and about
the planned evaluation and treatment. In some instances a telephone call to the referring
physician or at least the office is best with a follow-up letter. Such circumstances include
a request that the patient be seen the same day as the referral and the need to facilitate the
care of the patient. Be judicious; phone calls can be disruptive.
Availability
Evening and Saturday office hours have great appeal to patients. This is especially true
for single parents or parents who both work outside the home. Friday afternoon hours
also are beneficial. You may be the only specialist available at that time. Taking your
own calls as much as possible can be helpful. Your patients and referring physicians
appreciate being able to contact you if the need arises. The more accessible you are, the
better it is for building your practice.

HIGHLIGHTS
It is never too early to think about saving.
Where you live may be the most important decision you make.
Hiring an attorney helps avoid substantial problems.
BIBLIOGRAPHY
The AAO-HNS, through its practice management department, is an excellent initial resource for those
beginning the process of going into practice. The following are suggested readings. More publications are
available through the American Medical Association, American College of Surgeons, Medical Group
Management Association, and American College of Physician Executives. Financial planning information
can be obtained from any large brokerage firm.
Baum N, Henkel G. Marketing your clinical practice: ethically, effectively, economically. New York:
Aspen Publishers, 2000.
The Coker Group. Starting a medical practice. Chicago: American Medical Association, 1996.
The Coker Group. Assessing and improving billing and collections. Chicago: American Medical
Association, 2000.
The Coker Group. Managing the medical practice. Chicago: American Medical Association, 2000.
ENT Outreach. Building relationships in a new health care environment. American Academy of
OtolaryngologyHead and Neck Surgery, 2000.
Mabry CD, Kron IL, eds. Practice management for the young surgeon. Chicago: American College of
Surgeons, 1995.
Myers M Jr. Mastering the reimbursement process, 3rd ed. Chicago: American Medical Association, 2000.
Physician compensation systems. Chicago: American Medical Association, 2000.
Wayne M, Sotile MO. The medical marriage: sustaining healthy relationships for physicians and their
families. Chicago: American Medical Association, 2000.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

98 GENE THERAPY
Head & Neck SurgeryOtolaryngology
98




GENE THERAPY
SAMUEL J. CUNNINGHAM
GARY L. CLAYMAN
MICHAEL W. SICARD

S.J. Cunningham: Department of Otolaryngology, University of Texas Medical Branch at Galveston,
Galveston, Texas.
G.L. Clayman: Department of Head and Neck Surgery, University of Texas, MD Anderson Cancer Center,
Houston, Texas.
M.W. Sicard: Bobby R. Alford Department of OtorhinolaryngologyHead and Neck Surgery, Baylor
College of Medicine, Houston, Texas.


Gene Delivery Agents
Retroviral Vectors
Adenoviral Vectors
Adeno-associated Viral Vectors
Herpes Simplex Virus Vectors
Vaccinia and Poxviral Vectors
Nonviral Vectors
Gene Therapy for Neoplastic Disease
Immunomodulation
Cytotoxic Gene Therapy
Suppressor Gene Therapy
Antisense Gene Therapy
Other Applications
Ethical Implications
Conclusions
Chapter References
Medicine has evolved slowly over thousands of years to the point at which we can
understand, alter the course of, and eliminate disease. Whereas our crude surgical
interventions have evolved into what we consider sophisticated, well-thought-out
procedures, the instruments we wield have changed remarkably little. With the
introduction in the early 1970s of multimodality treatment, including radiation therapy
and chemotherapy, substantial improvements were made in patient survival. Despite
advances in surgical and radiation therapy techniques, no additional gains have been
realized. However, a conceptually new approach to the management of disease has
emerged. Dramatic advances in molecular biology, virology, biochemistry, and
biotechnology have introduced concepts and techniques once deemed fanciful to the
brink of therapeutic application. With many of the technical obstacles now cleared, gene
therapy has been accepted broadly in the spheres of medical and public policy.
The first hints that the transfer of genetic material was possible came in the early 1960s
(1). The development of selective cell culture media in which to demonstrate an altered
phenotype made it possible to show that mammalian cells can incorporate and express
foreign DNA. In the first experiments, investigators used hypoxanthine guanine
phosphoribosyl transferasedeficient cells from mutagenized rodent cell lines and cells
from patients with Lesch-Nyhan syndrome. These early methods, however, had an
inefficient transfer rate and produced relatively unstable expression of the transferred
gene.
Additional advances occurred in the mid-1970s with the development of a more efficient
method of DNA-mediated transformation and better methods of cutting and splicing
DNA molecules and monitoring recombinant DNA. The first viral vector model was a
recombinant SV40 tumor virus capable of transferring foreign marker DNA sequences
efficiently into mammalian cells (2). This viral vector model was established, and other
viral vectors soon followed.
In 1980, a highly controversial but landmark experiment was performed by Cline et al.
These investigators had had success with in vitro introduction of the human globin gene
into irradiated murine bone marrow cells by means of calcium phosphate transfection.
Cline proceeded to transfect bone marrow cells in vitro with plasmids containing the
human globin gene and reinfusing the transfected cells into patients with thalassemia (3).
These studies had not been not approved by Cline's institutional review board and were
much decried by his institution, the National Institutes of Health (NIH), and others. The
question now was not whether or when gene therapy would become a reality, but how.
The initial human gene therapy trials, approved by the NIH and the Recombinant DNA
Advisory Committee (RAC) in May 1989, were gene marker studies with no direct
therapeutic value. In these early studies, a gene from the Escherichia coli bacterium
coding for neomycin resistance was transferred ex vivo into tumor-infiltrating
lymphocytes (TILs). The transduced TILs were injected into five patients. Later analysis
of the patients' peripheral blood revealed persistence of the transduced lymphocytes for
up to 189 days. Moreover, analysis of biopsies of the tumors showed that the transfected
lymphocytes preferentially localized to sites of metastatic tumor and could be detected up
to 64 days after therapy (4).
The first clinical gene therapy trial began in September 1990. Using a retroviral vector,
Anderson et al. at the NIH transferred the gene for adenosine deaminase into collected
lymphocytes of a patient with hereditary adenosine deaminase deficiency (5). These
patients with severe combined immune deficiency had transient resolution of disease that
correlated with survival of the transfected lymphocytes. Although only a temporary
treatment, this first successful somatic gene therapy generated great enthusiasm and a
glimmer of hope for a long list of diseases likely to be controlled with gene therapy.
In 1998, when the last edition of this book was published, 107 phase I and II gene therapy
protocols had been approved by the NIH RAC. As of this writing, that list has expanded
to 332 protocols that include 30 gene marker protocols, the other 302 protocols are of
therapeutic intent (6). Of the 302 therapeutic protocols, 208 involve cancer therapy; the
others include therapy for inherited monogenic diseases, therapy for infection with
human immunodeficiency virus, cardiovascular disease, neurologic disorders, and others.
Fifteen of the 208 protocols addressing cancer involve gene therapy for squamous cell
cancer of the upper aerodigestive tract. Internationally, there are an additional 36 gene
therapy protocols, only one of which is for management of squamous cell carcinoma of
the upper aerodigestive tract (6).
GENE DELIVERY AGENTS
Any usefulness of gene therapy as a treatment is limited by the means of effectively
delivering the desired gene in sufficient quantity to its respective target cells without
adversely affecting nearby nontarget cells or the host. The methods of gene delivery are
based on viral and nonviral vectors and on administration of naked DNA (Table 98.1).
Vectors that have already been applied in clinical trials are based on retroviruses,
adenoviruses, adeno-associated viruses, vaccinia viruses, canarypox virus, herpes simplex
virus, cationic liposomes, and polylysine-DNA complexes (7). These vectors, viral and
nonviral, must be nontoxic to the patient and possess immunogenic properties in patients
only when desired, as in the case of genetic immunization. The targeting of vectors to the
desired cell population must be specific, must maintain expression of the transduced gene
for an adequate time and must obtain the desired gene function. The following discussion
compares and contrasts these properties and others for various gene therapy vectors.

TABLE 98.1. GENE THERAPY DELIVERY
METHODS



Gene therapy is administered by means of one of two methodsin vivo gene delivery or
ex vivo gene delivery. In vivo gene delivery is achieved by means of direct introduction
of the vector with the therapeutic gene into the target tissues. Ex vivo gene delivery
involves removing a portion of the target tissue or cells from the patient and transducing
them with the recombinant vector. These transduced cells are then placed back into the
patient.
Retroviral Vectors
Retroviruses are widely used as gene delivery vectors in gene therapy protocols, the most
common being based on the Ma-loney murine leukemia virus. The genus retroviridae
also includes lentiviruses, such as human immunodeficiency virus type 1 (HIV-1) and
feline immunodeficiency virus (FIV), and the foami viruses (human and simian).
Characteristics of the retroviral vectors are summarized in Table 98.2. Retroviruses are
RNA viruses that integrate their genomes into host cell chromosomes. This integration
can facilitate stable gene expression in the host, but the integration is random, which
theoretically can lead to insertional mutagenesis of the host cell. Retroviral vectors infect
a broad range of cell types but only infect actively dividing cells and produce no toxic
effects in the host cells (7). Because the genome of these viruses is relatively simple, it is
possible to replace functional viral genes (gag, pol, env) with recombinant DNA, a
promotor, and a packaging signal to render viral replication incompetent. All retroviral
vectors have an insert capacity (transgene plus vector) of approximately 10 kb. The
deleted viral genes are supplied by the packaging cell line. Virus production can be
accomplished in relatively high titers (10
6
to 10
7
cfu/mL). However, these viral particles
can be rapidly degraded by complement when introduced into a patient. The retrovirus,
produced by the packaging cell line, binds to the receptor on the target cell, enters the
cell, and releases its genetic material into the cytoplasm. The RNA then undergoes
reverse transcription by means of a virally encoded reverse transcriptase to produce a
double-stranded DNA provirus. This provirus inserts itself into the host cell chromosome
in a stable but random manner and is retained during subsequent mitotic division.
Although this permanent integration can be desirable for replacement of monogenic
deletions that requires long-term gene expression, it may not be desirable for therapies
involving toxin production or induction of apoptosis, as in gene therapy for cancer.

TABLE 98.2. MAIN GENE DELIVERY SYSTEMS



Several biosafety issues exist with use of retroviral vectors. Insertional mutagenesis is
possible, whereby viral DNA is inserted into a regulatory region of the host cell
chromosomes and induces expression of oncogenes or inactivation of the function of
tumor suppressor genes. There also exists the possibility of producing, through
homologous recombination, virus particles that would be able to replicate in the host.
There also is the possibility of recombination with human endogenous retroviruses (7).
The other members of the retroviridae are the lentiviruses, composed of HIV-1 and FIV,
and the foami viruses. The lentiviruses have been assessed in preclinical trials as gene
transfer vectors, but have not been used as vectors in clinical trials. The HIV-1based
lentiviral vector will probably not be used in clinical trials because of the biohazard
issues involved in producing these vectors and because of risk of seroconversion to HIV-
1 among these patients (7). The FIV-based lentiviral vector is much safer to produce, and
the wild-type virus cannot infect humans, so seroconversion to FIV is not a concern (7).
The lentiviral vectors have the same characteristics as the retroviral vectors (Table 98.2).
The lentiviral vectors normally cannot infect a wide variety of cell types, but they can be
pseudotyped with retroviral or vesicular stomatitis virus envelopes to broaden their cell
tropism (Table 98.2). This pseudotyping also facilitates purification of the viral particles
from cell culture (7). The lentiviral vector can infect nondividing cells, making this
vector useful for a wider variety of gene therapy applications. An additional limitation of
the use of the lentiviral vector, as opposed to the disadvantages of the use of retroviruses,
was detection of regulatory proteins in the earlier lentiviral vectors (Table 98.2).
The foami virusbased vector has profiles similar to those of the other retroviridae. They
can transduce a wide variety of cell types, even without being pseudotyped with vesicular
stomatitis virus glycoprotein or retroviral envelopes (7). They can infect dividing cells
and to a lesser extent nondividing cells, and are resistant to complement-mediated lysis.
Foami virus genomes are stably but randomly integrated into cellular chromosomes and
can be produced at relatively high titers of 10
6
to 10
7
cfu/mL. The foami viral vectors
have an insert capacity of about 14 kb, which is slightly larger than that of the
lentiviruses and retroviruses. The negative aspects of foami viral vectors are similar to the
limitations of other retroviridae; human seroconversion to foami viruses has been
reported. There has been no evidence that foami viruses can be transmitted among
humans or that these viruses are pathogenic to humans (Table 98.2), so this
seroconversion is not a serious issue.
Adenoviral Vectors
The adenoviruses were first used in clinical gene therapy protocols in 1993. Since that
time, extensive research has been done to improve use of these viruses as a gene transfer
vector. This research has yielded advances in adenoviral vector design that have resulted
in wider application in preclinical studies and in therapy (7). Adenoviruses are relatively
safe for patients, producing only coldlike symptoms. Adenovirus has been shown to be
safe and well tolerated as a vaccine given to millions of military recruits.
The adenovirus vector is a DNA virus that binds to the cell and undergoes endocytosis.
The endosome is disrupted, and viral DNA is released. This adenoviral DNA rarely
integrates into the host genome but remains as a nonreplicating extrachromosomal entity
called an episome. With the help of an accompanying promotor sequence, the desired
gene of interest and the viral structural genes are transcribed into RNA. The introduced
gene persists for 7 to 42 days (8), although expression for up to a year has been observed.
The adenovirus vector is made replication deficient through deletion of the E1 region of
the viral genome (9). Adenoviruses can be produced in high titers (10
12
cfu/mL) in cell
lines that have been stably transformed with the adenovirus E1 gene (7). Adenovirus
vectors have many other desirable attributes (Table 98.2). Because they can be produced
in high titers, adenovirus vectors can express high levels of the transduced gene. This
expression is only transient, because of the vector DNA is never incorporated into the
host cell genome. Although this transient transduction is not a desirable characteristic in
therapeutic strategies that require stable expression, such as monogenic disorders, it has
been useful in targeting the destruction of neoplastic cells in cancer therapy.
Adenovirus vectors have a broad cell tropism and can transduce actively dividing and
nondividing cells. The virus has known tropism for cells of the upper aerodigestive tract
but lack specificity for tumor cells, rendering nondiseased cells susceptible to
transduction. Progress has been made in altering adeno-virus vector tropism to increase
target cell specificity in squamous cell carcinoma of the head and neck (10). Adenovirus
vectors can accommodate large DNA inserts, 7 to 8 kb. Even larger DNA inserts are
possible when an equivalent part of the viral genome is deleted (7).
The utility of the adenovirus vector is severely limited by its immunogenic properties.
Because of the transient nature of its gene expression, repeated administration of the
adenovirus vector usually is needed. This repeated exposure induces a humoral immune
response and produces neutralizing antibodies to the adenovirus vector. Many patients
have acquired immunity to the adenovirus before gene therapy (7). These antibodies can
neutralize adenovirus vector particles during or even before the gene transfer process
(Table 98.2). The host also can produce a cellular immune response to the transduced
cells, further depleting that cell population (7).
Adeno-associated Viral Vectors
The adeno-associated virus (AAV) was first approved for use in a human gene transfer
protocol in 1994. Adeno-associated virus is a single-stranded DNA parvovirus that has no
associated human disease. Like adenovirus, AAV has a broad cell tropism and can infect
nondividing cells. Its characteristics are listed in Table 98.2. The AAV can maintain
either a latent infection or a lytic phase, replicating only in the presence of a helper virus.
The AAV vector is produced by cotransfecting an AAV packaging cell line with the
AAV vector, in which the viral genes have been replaced with therapeutic DNA and a
separate plasmid containing the viral genes coding for AAV packaging components (7).
These packaging cells, cotransfected with the AAV vector and the packaging construct,
are infected with a helper virus (either an adenovirus or a herpesvirus) to initiate
replication of the recombinant AAV vector (7). This process yields recombinant AAV
vector in high titers (10
10
cfu/mL), but it is difficult to obtain pure stocks that are free of
helper virus (7). In the absence of the helper virus, the wild type AAV incorporates its
DNA predictably at the 19q13.4 location of the human genome. This predictable
integration of viral DNA is not conserved in the recombinant AAV vectors and can cause
cell mutagenesis. Because 19q13.4 has been implicated in chromosomal rearrangements
associated with chronic B-cell leukemia, it is uncertain whether AAV offers any
advantage over the random pattern of insertion of the retroviral vector. Evidence suggests
that AAV integration into both copies of chromosome 19 can cause cell death. Because
the AAV genome is small (5 kb), there is limited capacity for the size of therapeutic
genes (approximately 14 kb).
Herpes Simplex Virus Vectors
The characteristics of the herpes simplex virus (HSV) vector are outlined in Table 98.2.
Herpes simplex virus can be produced in relatively high titers (10
4
to 10
8
cfu/mL) and can
accommodate a transgene of up to 30 kb. Although it does not integrate into the host cell
genome, the HSV vector does allow for long-term expression of the transgene in neuronal
cells. The inflammatory and cytotoxic reactions elicited by the HSV vector among
patients has limited its use in human gene therapy trials. A mutant HSV (HSV-1716)
deficient in neurovirulence factor ICP34.5 has been identified (9). This mutant HSV does
not replicate in neural tissues but appears to replicate in tumor cells with subsequent lysis
of the tumor cells. This finding suggests a role for it as a combined gene delivery vector
and a tumor-specific cytolytic virus (9).
Vaccinia and Poxviral Vectors
Vaccinia virus, a member of the poxviridae, has the longest history of clinical use among
humans. The history dates to the late 1700s, when Jenner described the benefits of
exposure to vaccinia (variola) in the management of smallpox. Vaccinia, as a result, was
the first widely used vaccine and eradicated smallpox. Although wild-type vaccinia
infection is invariably cytolytic, less virulent pox virus vectors, such as modified vaccinia
Ankara and fowl pox, are available as gene transfer vectors (11). The relative safety,
broad cell tropism, large insert capacity (up to 25 kb of DNA), and ease of production
make these vectors useful for gene therapy. There are limitations to their utility, however.
Because the vaccinia virus vectors do not integrate their genome into host cell
chromosomes, there is only transient expression of the transgene. In addition, the
immunogenic nature of the vaccinia virus raises questions about its use as a gene transfer
vector. Production of neutralizing antibodies may limit the number of viral particles
carrying the transgene. However, studies of revaccinated subjects show little or no
residual immunity from their first exposure to the virus. Transgenes have been
successfully expressed even after multiple inoculations with the same recombinant pox
virus (11). Vaccinia and other pox virus vectors have a remarkable potential. Further
improvements should greatly broaden their usefulness.
Nonviral Vectors
Nonviral vectors used as gene delivery agents include cationic liposomes, DNA-protein
complexes, and mechanical administration of naked DNA. The attributes of these vectors
are summarized in Table 98.2. Unlike their viral counterparts, these vectors are not
infectious and have a low degree of toxicity to the patient. These vectors facilitate
delivery of large DNA fragments and, even more so, the delivery of oligonucleotides.
Thus the vectors are amenable to antisense therapy to inhibit selective gene expression.
This strategy is the subject of many studies in cancer research. Naked DNA also can be
introduced into cells by physical means such as electroporation, bombardment with gold
particles covered with DNA, and liposome- and receptor-mediated gene transfer. With
any of these methods, cell targeting is not specific, there is low transduction efficiency,
and there is only transient gene expression, making the methods less useful for in vivo
applications (Table 98.2). Cationic liposomes induce host immune responses to
unmethylated CpG motifs on bacterial DNA, further limiting their application (7).
Further developments with these vectors should lead to wider applications for them as
gene delivery agents.
GENE THERAPY FOR NEOPLASTIC DISEASE
Gene therapy for the management of cancer is an ever-expanding field. With advances in
the basic sciences and vector design, many different clinical protocols addressing cancer
are being evaluated. Gene therapy remains an attractive option for head and neck cancer
because of the accessibility of the tumors to gene therapy, the ability to directly monitor
the tumors, and the need for new therapies for these aggressive neoplasms (12). Several
strategies are being pursued, including immunomodulation, cytotoxic gene therapy,
tumor suppressor gene therapy, and antisense therapy.
Immunomodulation
Several strategies have been used to increase the host immune response to a tumor,
including genetic modification of TILs, enhanced immunogenicity of in vivo tumors, and
ex vivo enhancement of tumor immunogenicity. Although these ap-proaches have been
viewed as the equivalent of vaccination against a tumor, in reality they are not. They are
targeted against established tumors and metastasis rather than serving as preventive
strategies, as in vaccination programs.
Several trials have focused on TILs. In one trial, TILs were isolated from patients with
metastatic melanoma and exposed to a retroviral vector to allow transfer of the gene for
tumor necrosis factor alpha (TNF-). The transduced TILs were reinfused to determine
whether elevated local concentrations of this toxic protein could be achieved without the
substantial toxicity induced by systemic administration. The TILs did appear to localize
to areas of disease and produce TNF (13). In a phase I trial of TNF- with or without
interleukin 2 (IL-2) in the treatment of 39 patients with cancer, however, no evidence of
tumor response was found (14). In animal studies of oral cancer, the use of adenoviral IL-
2 was limited by the level of its expression and toxicity (15). However, nonviral IL-2,
delivered by means of direct injection of human IL-2 (hIL-2) conjugated to a cationic
liposome, induced local expression of multiple cytokines, showed treatment-specific
antitumor effects, and circumvented previously reported IL-2 toxicity (16). The results of
these studies show the potential of immunomodulation, alone or in combination with
surgery or other treatments, in addressing head and neck cancer. Other potential
therapeutic genes being considered include IL-4, interferon-alpha (IFN-), interferon-tau
(IFN-), and granulocyte-macrophage colony-stimulating factor (GM-CSF).
Attempts to stimulate the host's immune response against tumor by means of in vivo
immunotherapy have produced mixed results. Studies have shown that tumor cells can
escape early detection because of decreased expression of class I major
histocompatibility complex (MHC) antigens, namely human leukocyte antigen B7 (HLA
B7), thus circumventing cytotoxic T-cell lysis of the tumor cell. Direct injection of
liposome-mediated DNA encoding class I MHC antigen and B2-microglobulin into
metastatic nodules for the management of melanoma, hepatic metastasis of colon cancer,
and sarcoma cell lines has been reported with limited success (17); however, studies of
this approach in the management of squamous cell carcinoma of the head and neck have
produced promising results (12).
Ex vivo approaches have been used to enhance the immunogenicity of tumor cells.
Cancer cells are harvested from the patient, cultivated ex vivo, transduced with a
therapeutic gene, irradiated, and reintroduced into the patient. The therapeutic genes used
so far have included IL-2, IL-4, GM-CSF, and IFN-. Heterologous tumor lines have
been used to enhance the immunogenicity of the injected cells. Although some
immunologic responses have been shown and many directly injected nodules have
apparently responded to immunomodulation, further refinement of this treatment
modality is needed. Work continues in this area of gene therapy.
Cytotoxic Gene Therapy
Introduction of a gene that ultimately expresses or produces a toxin in the targeted cell is
the second most common gene transfer approach after immunotherapy. The inserted gene
has been, nearly universally, the HSV thymidine kinase (HSV-tk) gene. The HSV-tk gene
expresses a viral thymidine kinase foreign to mammalian cells but phosphorylates the
prodrug ganciclovir into a toxic compound that terminates DNA synthesis.
Concentrations of the toxin can be achieved that are lethal to normal mammalian cells. A
bystander effect has been described in which surrounding nontransduced cells also are
killed. Proposed mechanisms of this action are the transfer of toxic metabolites through
gap junctions or through endocytosis of cellular remnants of the dying tumor (12). It also
has been suggested that the death of HSV-tktransduced tumor cells improves immune
response to any surviving tumor cells.
Although the primary focus of human cytotoxic gene therapy studies has been
glioblastoma, other studies include management of leptomeningeal carcinomatosis,
mesothelioma, meta-static ovarian and breast cancers, and squamous cell cancer of the
head and neck. Studies of human head and neck cancer conducted with treatment of
immunosuppressed mice with adenovirus- and retrovirus-mediated HSV-tk gene transfer
showed tumor regression and extended survival periods (12). Investigation with
immunocompetent mice given implants of head and neck cancer cells from humans
confirmed the efficacy of this treatment, but the HSV-tk gene was detected in distant
organs when the viral dose was high (12).
O'Malley et al. (18) examined the possibility of combined gene therapy involving
adenovirus-mediated transfer of the HSV-tk and IL-2 genes to an established squamous
cell cancer in a mouse model. Considerable tumor regression was achieved with either
HSV-tk alone or with IL-2 and HSV-tk compared with IL-2 alone or control conditions.
The combined treatment appeared to have a synergistic effect in tumor regression and
survival studies (18).
In another form of cytotoxic gene therapy, the cytosine deaminase gene is used. This
gene expressed in transduced tumor cells produces the enzyme cytosine deaminase,
which converts the prodrug 5-fluorocytosine to the highly toxic 5-fluorouracil. This
method of cytotoxic gene therapy allows higher concentrations of 5-fluorouracil to
accumulate in the tumor than would be possible with systemic therapy (12). This system
used in an orthotopic immunocompetent animal model of head and neck cancer delayed
the growth of tumors. In some cases, there was frank tumor regression or complete cure
(19).
Suppressor Gene Therapy
Tumor suppressor genes are naturally present in cells and appear to be involved in cell
growth and replication. Mutation, deletion, or methylation of these genes can lead to
uncontrolled cellular growth. Likewise, protooncogenes participate in normal cellular
signaling, transduction, and transcription. A single mutant allele of one of these genes, an
oncogene, may be needed for certain malignant transformations. Multiple genetic
abnormalities are present in the progression to invasive carcinoma. After histopathologic
and chromosomal analyses, Califano et al. (20) proposed that squamous cell cancer of the
head and neck undergoes a series of molecular events involving both oncogenes and
tumor suppressor genes in a distinct order; however, in individual tumors, it is the
accumulation of these events that determines tumor progression. Results of several
studies have shown, however, that correction of a single genetic defect in a cell can
reduce or eliminate critical characteristics of the malignant phenotype.
The p53 tumor suppressor gene has been a subject of intense investigation in a wide
range of human cancers. Mutations in the p53 gene are some of the most common known
genetic defects in cancer. They can occur in more than half of all squamous cell cancers
of the head and neck. Wild-type p53 is dominant over its mutant gene and selects against
proliferation when transduced into cells with the mutant gene or endogenous wild-type
p53 gene. Wild-type p53 transduced at comparable levels into nonmalignant cells does
not affect growth of the cells (12).
Suppression of tumor cell growth has been investigated in squamous cell cancer tumor
lines containing either endogenous wild-type or mutated p53. Both tumor types manifest
programmed cell death, or apoptosis. Transient suppression of cell growth also has been
shown and suggests a role of p53 as a reversible cell-cycle-checkpoint regulator at the
G1-S cell cycle interface (12). Together these results suggest that transduction of the p53
gene into tumor cells may have an important role in the induction of apoptosis in human
head and neck cancer cell lines and as a strategy for cancer gene therapy.
Preclinical studies with mouse xenograft models showed that delivery of the wild-type
p53 gene with an adenovirus vector reduced tumor growth (12). Further clinical
investigation of the recombinant adenovirus-p53 (Ad-53) vector showed that the Ad-53
was safe for patients and produced objective antitumor activity (12). These results led to
phase I and phase II studies of Ad-53 gene transfer in the treatment of patients with
advanced, locoregionally recurrent squamous cell carcinoma of the head and neck. The
studies showed an increased survival rate among patients with resectable but historically
incurable disease (21). These clinical investigations illustrated the usefulness of p53 gene
replacement therapy in the care of patients with cancer of the head and neck.
Even in light of these encouraging results, p53 gene replacement is still problematic. The
p53 gene must be replaced in nearly all cells of the tumor, because there is less of a
bystander effect than in other gene replacement strategies, such as cytotoxic gene
therapy. In addition, cancer of the head and neck is an accumulation of many genetic
aberrations. Simply replacing one defect may not be sufficient to induce apoptosis. In
fact, overexpression of the oncoprotein MDM2 has been shown to block the function of
p53 (12). These findings have led to investigation of combination of p53 therapy with
other treatments, such as surgery, radiation therapy, chemotherapy, and other gene
therapies. Besides directly inducing apoptosis, p53 has been shown in animal models to
increase the responsiveness of tumors to radiation therapy and chemotherapy through the
apoptotic pathway. Human studies are under way to combine p53 gene replacement
therapy with chemotherapy (12).
Another strategy focuses on the adenoviral E1B gene. This gene encodes a 55-kd protein
that binds to the tumor suppressor p53 protein. The E1B gene is essential for virus
reproduction and is thought to allow infected cells to divide because of its binding to the
p53 protein. In the adenovirus ONYX-015, the E1B gene is deleted, and the virus is
incapable of reproduction except in cells deficient in normal p53 protein. This mutation
occurs frequently in many tumor types, including squamous cell cancer of the head and
neck. Mutant adenoviruses deficient in E1B protein can replicate and lyse p53-deficient
human tumor cells in vitro and in an in vivo mouse model (12). Clinical trials have
shown intratumoral injection of the ONYX-015 virus to be feasible, well tolerated, and
associated with biologic activity (22). Further studies of intratumoral injection of ONYX-
015 alone and in combination with other therapies such as systemic chemotherapy and
radiation therapy are needed.
An additional adenovirus-based gene therapy strategy targets the E1A adenoviral gene.
This viral gene suppresses the Her-2/neu oncogene, which is overexpressed in many head
and neck cancers (12). The E1A gene also increases epithelioid differentiation and can
reduce cellular proliferation in cancer of the head and neck (12).
Other tumor suppressor genes, p16 and p21, have been the focus of research efforts. The
p16 gene encodes a cell-cycle protein that inhibits cyclin-dependent kinases (CDKs) 4
and 6. These CDKs phosphorylate the retinoblastoma protein, which is instrumental in
progression of cells from G1 to S phase. Loss of normal p16 gene function therefore is
expected to lead to uncontrolled cell growth. Studies have shown a high frequency of
homozygous deletions in the gene coding for the p16 protein in a variety of human tumor
cell lines (12). The p21 protein is a critical downstream effector in the p53-dependent
pathway of growth control. Like p16, it causes growth arrest through inhibition of CDKs.
Inactivation or mutation of these tumor suppressor genes has been correlated with
development of head and neck cancer, and both p16 and p21 can stabilize or reduce
established head and neck cancer in mouse models (12).
Antisense Gene Therapy
Expression of a gene usually can be inhibited, in effect, by blocking and thereby
inhibition of production of its protein product. Introduction of an RNA strand
complementary to the gene or messenger RNA strand of interest can inhibit activity of
several known oncogenes (Table 98.3). Oligonucleotides that are anticomplementary, or
antisense, to either RNA or DNA targets also can be introduced. Currently approved
clinical protocols include antisense therapies for c-myc and c-fos, which are known to be
overexpressed in breast cancer; insulin-like growth factor I gene in glioblastoma cells;
and k-ras in non-small-cell carcinoma of the lung. Antisense therapy against the
epidermal growth factor receptor in head and neck cancer has been evaluated in animal
studies with encouraging results (23). Although promising, the strategy of administering
antisense oligonucleotides for selective gene inhibition must overcome technical hurdles
such as targeting and expression.

TABLE 98.3. ONCOGENES AND TUMOR
SUPPRESSORS



OTHER APPLICATIONS
Numerous other applications have been conceived and are being explored. Much clinical
investigation has been conducted to enhance the resistance of bone marrow to
chemotherapy as protection against bone marrow suppression, which would allow an
increased dose of chemotherapy without the accompanying toxicity related to
immunosuppression.
Many inherited diseases frequently encountered by the otolaryngologist may be amenable
to gene therapy. For example, cystic fibrosis has been shown to be caused by a mutation
in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Recombinant
adenovirus vectors, AAV vectors, and liposomal vectors containing the normal CFTR
gene have been given to persons who have cystic fibrosis and each has produced
encouraging results. The most promising are those obtained from the use of AAV and
liposome vectors. Functional, though transient, CFTR has been reported in these studies
(24). Gene therapies for common disorders, including arteriosclerosis, rheumatoid
arthritis, hyperlipidemia, diabetes mellitus, neurologic, and infectious diseases, have been
proposed and invest-igated. Therapy to prevent the sequence from premalignant disease
to malignant transformation has been explored with success. Trials and other pending
protocols for such therapies are being regulated closely by both the NIH and the U.S.
Food and Drug Administration. Once important issues regarding optimum gene delivery
and potential toxicities are addressed, the spectrum of disorders open to gene therapy will
be even more vast.
ETHICAL IMPLICATIONS
The focus of this chapter has been gene therapy for somatic cell disorders as opposed to
germline gene therapy. Although somatic cell gene therapy is now widely accepted in the
medical community and by the public in general, germline therapy is not. Attempts to
correct the cells of patients so that future offspring do not have a specific genetic defect
or to affect an inheritable attribute remain highly controversial. In the early 1980s, the
President's Commission for the Study of Ethical Problems in Medicine and Biomedical
and Behavioral Re-search was established to address these concerns and others related to
the growing field of gene therapy. The RAC was established after congressional hearings
were held on issues in genetic engineering.
As phase I and II trials with cancer patients are initiated and evolve, questions of
nonmaleficence and beneficence arise. Whereas the avoidance of harm to one's patients is
not novel or confined to gene therapy, the sense of hope instilled in an altruistic patient
by a treatment option as glamorous as gene therapy must be approached warily and
should not be introduced by the physician. As always, the concept of informed consent
and the respect for a patient's rights of refusal are essential (25).
The issues involved with germline gene therapy are numerous and clearly are unsettled.
Although no trials have been proposed, the evolution from somatic cell therapy to what
some experts view as preventive therapy raises a multitude of ethical and moral issues.
The slippery slope arguments abound, perhaps justifiably, that germline correction of
what would be inarguably viewed as truly genetic diseases could digress into genetic
enhancement of desirable characteristics. With this technology rapidly approaching, it is
appropriate to broach these issues before such technology is established (26).
CONCLUSIONS
The field of gene therapy continues to grow and mature. It remains to be seen whether
these methods and strategies ultimately develop into a therapeutic reality, and the time
course for their maturation remains obscure. Increased knowledge of the pathogenesis of
many diseases is critical. The field of gene therapy is evolving, but at this time the
greatest immediate potential lies in the possibility of an increase in the understanding
provided by gene transfer studies to address our knowledge of the genetic basis and
regulation of carcinogenesis. As the field progresses and delivery systems become more
refined, gene therapy may provide adjunctive therapy to surgical management of head
and neck cancer and someday may be used in the management of premalignant disease.

HIGHLIGHTS
The field of gene therapy is rapidly expanding in both the basic
sciences and clinical trials.
Mediators of gene therapy delivery can be categorized broadly
into viral and nonviral or physical methods.
Nonviral methods of gene transfer are inefficient and lack
specificity.
Viral methods involve the use of replication-incompetent virus
and insertion of gene sequences and promoters of interest.
Retroviral vectors insert genetic material in a stable but random
pattern into the host DNA of an infected cell. Retroviral
integration requires an actively dividing host.
Adenoviral vectors readily infect quiescent or actively dividing
cells. Integrated genetic material is incorporated as an
extrachromosomal, nonreplicating entity and can be expressed
for a limited time.
Gene therapy for neoplastic disease is an area of increasing
interest. Strategies focus on immunomodulation, cytotoxic gene
therapy, tumor suppressor genes, and oncogenes.
Increasing evidence suggests that an accumulation of genetic
events determines tumor progression. Correction of a single
defect in a cell may eliminate critical characteristics of the
malignant phenotype.
Gene therapy remains an attractive option for head and neck
cancer because of accessibility of the tumors to gene therapy,
ability to directly monitor the tumors, and the need for new
therapies for these aggressive neoplasms.
In the future, gene therapy can offer treatment alternatives for
numerous applications, including inherited disease,
premalignant and malignant disease, and degenerative
disorders.
The ethical principles involved in medicine and scientific
research must be maintained in the development of this
expanding frontier.
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8. Mulligan RC. The basic science of gene therapy. Science 1993;260:926932.
9. Green N, McNeish I. Principles of gene therapy: prospects for the treatment of head and neck
cancer. J Laryngol Otol 1998;112:913920.
10. Kasono K, Blackwell J, Douglas J, et al. Selective gene delivery to head and neck cancer cells via
an integrin targeted adenoviral vector. Clin Cancer Res 1999;5:25712579.
11. Mastrangelo MJ, Eisenlohr LC, Gomella L, et al. Poxvirus vectors: orphaned and
underappreciated. J Clin Invest 2000;105:10311034.
12. Gleich LL. Gene therapy for head and neck cancer. Laryngoscope 2000;110:708726.
13. Rosenberg SA. Gene therapy for cancer. JAMA 1992;268:241619.
14. Rosenberg SA, Lotze MT, Yang JC, et al. Experience with the use of high-dose interleukin-2 in
the treatment of 652 cancer patients. Ann Surg 1989;210:474485.
15. O'Malley BW Jr, Li D, Buckner A, et al. Limitations of adenovirus-mediated interleukin-2 gene
therapy for oral cancer. Laryngoscope 1999;109:389395.
16. Li D, Jiang W, Bishop JS, et al. Combination surgery and nonviral interleukin-2 gene therapy for
head and neck cancer. Clin Cancer Res 1999;5:15511556.
17. Nabel GJ, Nabel EG, Yang ZY, et al. Direct gene transfer with DNA-liposome complexes in
melanoma: expression, biologic activity, and lack of toxicity in humans. Proc Natl Acad Sci U S A
1993;90:1130711311.
18. O'Malley BW Jr, Cope KA, Chen S, et al. Combination gene therapy for oral cancer in a murine
model. Cancer Res 1996;56:17371741.
19. Hamstra DA, Rice DJ, Fahmy S, et al. Enzyme/prodrug therapy for head and neck cancer using a
catalytically superior cytosine deaminase. Hum Gene Ther 1999;10:19932003.
20. Califano J, van der Riet P, Westra W, et al. Genetic progression model for head and neck cancer:
implications for field cancerization. Cancer Res 1996;56:24882492.
21. Clayman GL, Frank DK, Bruso PA, et al. Adenovirus-mediated wild-type p53 gene transfer as a
surgical adjuvant in advanced head and neck cancers. Clin Cancer Res 1999;5:17151722.
22. Ganly I, Kirn D, Eckhardt SG, et al. A phase I study of onyx-015, an E1B attenuated adenovirus,
administered intratumorally to patients with recurrent head and neck cancer. Clin Cancer Res
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

99 GUIDELINES TO PATIENT CARE
Head & Neck SurgeryOtolaryngology
99




GUIDELINES TO PATIENT CARE
THEODOROS N. TEKNOS
JOHN U. CONIGLIO
JAMES L. NETTERVILLE

T.N. Teknos: Department of OtolaryngologyHead and Neck Surgery, University of Michigan Hospitals,
Ann Arbor, Michigan.
J.U. Coniglio: Division of OtolaryngologyHead and Neck Surgery, Strong Memorial Hospital, University
of Rochester, Rochester, New York.
J.L. Netterville: Department of Otolaryngology, Vanderbilt University Medical Center, Nashville,
Tennessee.


Initial Evaluation
History
Physical Examination
Adjuncts to Physical Examination
General Evaluation and Laboratory Studies
Panendoscopy
Metastatic Evaluation
Treatment Guidelines
Posttreatment Rehabilitation
Long-Term Follow-Up
Summary
Chapter References
Despite increasing public awareness concerning the detrimental effects of tobacco and
alcohol abuse, head and neck cancer remains a major contributor to the annual incidence
of cancer in the United States. Each year, 78,000 persons are found to have a malignant
tumor of the head and neck, and 17,500 die of this disease (1,2). This constitutes 7% of
all cancers diagnosed and 4% of all cancer deaths annually (2). Thirty-three percent of all
patients with head and neck cancer eventually die of the disease (3). Many of these deaths
can be attributed to delay in diagnosis and inadequate initial treatment. State-of-the-art
care of these patients requires a multispecialty approach (Table 99.1) to address all of
their needs.

TABLE 99.1. HEAD AND NECK ONCOLOGY
TEAM



INITIAL EVALUATION
The initial office or hospital evaluation is the single most important encounter for
gathering relevant patient information and establishing a trusting rapport with the patient.
As with any patient encounter, the essential components of a thorough evaluation include
a detailed history, review of systems, physical examination, differential diagnosis, and
assessment of findings.
History
In histories of a patient with cancer of the head and neck, more mistakes are caused by
errors of omission than by errors of commission. Therefore, a detailed and focused
evaluation must be obtained. For any smoker 35 years or older, the presence of any of the
signs and symptoms in Table 99.2 is considered indicative of head and neck cancer until
proved otherwise (1).

TABLE 99.2. PROGRESSIVE SIGNS AND
SYMPTOMS OF HEAD AND NECK CANCER



After the presenting symptoms are characterized, the patient is questioned about potential
risk factors. Tobacco and alcohol use account for approximately 80% of these cancers
and places users of these drugs at a 15-fold greater risk of squamous cell carcinoma than
are nonsmokers and nondrinkers (1,4). Other, less recognized risk factors of malignant
disease also should be identified. These include (a) exposure to ultraviolet and ionizing
radiation, Neoprene, or inorganic arsenics, burns, and riboflavin deficiencies for skin
cancers; (b) exposure to wood dust, leather manufacturing, nickel refining, radium dial
painting, Thorotrast, or mustard gas for cancer of the nose and paranasal sinuses; (c)
exposure to or ingestion of nitrosamines, salted fish, or Epstein-Barr virus types 2 and 3
or vitamin C deficiency for nasopharyngeal carcinoma; (d) chewing of betel nut, snuff, or
tobacco, reverse smoking, syphilis, vitamin B and riboflavin deficiencies, and chronic
irritation for oral carcinoma; (e) exposure to asbestos, coke ovens, or wood dust or
riboflavin deficiency for laryngeal and hypopharyngeal carcinoma; (f) radiation exposure,
iodine deficiency, or genetic inheritance for thyroid cancer; and (g) radiation exposure
and Inuit or Aleut heritage for salivary gland neoplasms (5).
A detailed medical history, surgical history, medication history, and review of systems
are elicited. The host performance scale is assessed for each patient through questions
about daily activities and current level of impairment (6,7). This information is critical in
assessing the patient's perioperative risk status and identifying any medical illnesses that
must be managed before therapeutic intervention for cancer.
Physical Examination
A complete physical examination is necessary to make a diagnosis and to identify the
presence of comorbid conditions. Comorbidity is an important feature among patients
with head and neck cancer and affects overall survival (8). Performance of a head and
neck examination alone is condemned. Although examination of the head and neck can
be difficult, no examination is considered complete until all mucosal surfaces of the nasal
cavity, nasopharynx, oral cavity, oropharynx, hypopharynx, and larynx have been clearly
seen. Inspection of the skin and scalp, pneumatic otoscopy, and a complete cranial nerve
examination must be documented clearly. Inspection, palpation, and auscultation of the
neck and bimanual palpation of the oral cavity and oropharynx must be accomplished in
each case.
The physical examination accomplishes the following: (a) characterization of the primary
tumor, if present, with regard to size and extent, (b) definition and characterization of
neck disease, and (c) exclusion of synchronous tumors or other diseases. Understanding
the anatomic features of each nodal group and the patterns of spread for a particular
primary site is crucial for identifying an unknown primary tumor in a patient with known
neck disease (1,9). Conversely, finding an unusual drainage pattern for a known primary
tumor can alert the examiner to the presence of a second primary lesion (9).
Adjuncts to Physical Examination
A physical examination has limitations. Areas particularly prone to incorrect diagnosis
include bony, soft-tissue, or great-vessel involvement by tumor and assessment of neck
disease. When these aspects of the examination are in question, appropriately ordered
radiographic studies and fine-needle aspiration (FNA) are invaluable adjuncts to physical
examination.
With regard to the primary tumor, computed tomography (CT) and magnetic resonance
imaging (MRI) offer valuable information concerning size and extent of disease often not
appreciated at initial evaluation. In comparative studies, CT was found to be superior to
MRI in examination of the oral cavity and other anatomic regions in which bonesoft
tissue interfaces are critical (10,11). Conversely, T1-weighted MR images with contrast
enhancement facilitate recognition of oropharyngeal and laryngeal tumor. Magnetic
resonance imaging also is useful in delineating tumor from inspissated secretions in
carcinoma of the paranasal sinuses. Images obtained with T2-weighted sequences are
ideal for determining the extent of carcinoma of the floor of the mouth (10,11). If bony
(mandibular or cervical spinal) involvement by the primary tumor is questionable,
panoramic radiography, CT, or bone scanning is invaluable. Physical examination alone
is only 30% sensitive in assessment of bony invasion (12). Although bone scans have
been shown to have a high false-positive rate, none of the imaging studies has a high
false-negative rate (13). Therefore normal findings with any imaging technique usually
preclude bony involvement (12,13).
Radiographic studies perhaps are most useful in detecting occult nodal metastases.
Computed tomography and MRI can depict metastases as small as 6 mm and can depict
early extracapsular spread (14). Stevens et al. (15) found 70% accuracy in the detection
of nodal metastasis by means of palpation alone. With the addition of CT evaluation,
however, accuracy rose to 93% (15,16). Magnetic resonance images obtained with T2-
weighted sequences are useful but are not as sensitive as contrast-enhanced CT in
evaluation for neck disease.
Computed tomography and MRI also are critical in assessment of carotid involvement.
The CT criterion for carotid artery invasion has been defined as more than 25%
effacement of the circumference of the artery (17). Prospective studies have shown CT
accurately excludes patients without carotid involvement but has a high false-positive
rate of 94% (17). Magnetic resonance imaging, on the other hand, is accurate in
prediction of carotid artery invasion, with a sensitivity of 100% and a specificity of 87%
(17). Magnetic resonance imaging is particularly helpful in examinations of patients with
a history of radiation, because the low-intensity signal of fibrosis can be differentiated
from the high-intensity signal of tumor on T2-weighted images. Although infrequently
used, ultrasonography has 100% sensitivity and 75% specificity in the prediction of
carotid involvement (17).
In addition to imaging studies, FNA is a useful adjunct to physical examination. It is a
simple means with which to confirm histologic diagnosis of a neck mass. With current
technology, FNA can help identify squamous cell carcinoma, thyroid carcinoma, and
malignant tumor of the parotid gland meta-static to the neck with an accuracy of 92%,
96.2%, and 96.4%, respectively (18,19). This procedure has revolutionized office
evaluation of neck masses.
General Evaluation and Laboratory Studies
Once a head and neck surgeon has determined that malignancy is likely because of the
history and physical examination findings, the patient's general medical condition and the
presence of metastasis must be evaluated objectively before panendoscopy is performed.
Many patients with head and neck cancer have comorbidities owing to lifestyle. The
initial preoperative studies must examine all pertinent organ systems and help assess the
patient's perioperative risk status. If a patient smokes heavily, it is critical to assess
pulmonary function. The best assessment tool is pulmonary function tests combined with
measurement of arterial blood gases (20) and functional activity. Patients with poor
pulmonary reservemost accurately measured by means of spirometric analysis of
forced expiratory volume in 1 second (FEV
1
)are at high perioperative risk and are not
candidates for partial laryngeal procedures. Early identification of these patients allows
early treatment or prophylactic measures to prevent postoperative complications.
Cardiovascular status is an important consideration. At a minimum, electrocardiography
and chest radiography are needed. In a large prospective study (21), it was found that the
physician's subjective assessment of suspected coronary artery disease is as accurate as
results of stress tests and noninvasive studies and therefore is to be included in any
preoperative evaluation. If serious disease is suspected, invasive testing such as
catheterization and intervention is necessary before treatment is begun.
Hematologic evaluation (blood count, differential, and platelet count) confirms the
presence of anemia so that the condition can be corrected preoperatively with iron for
microcytic anemia and vitamin B
12
for macrocytic anemia. A leukocyte count less than 3
10
9
/L without a documented immunodeficiency state alerts the physician to the
likelihood of malnutrition (22). Finally, thrombocytosis believed to be caused by the
inflammatory response incurred by bacterial contamination of tumors is the greatest
predictor of postoperative wound infection (23). Attempts can be made at preoperative
sterilization of the tumor with antibiotics and aggressive postoperative parenteral
antibiotics to prevent this complication.
Hepatorenal dysfunction, electrolyte imbalances, and nutritional deficiencies are most
closely associated with a high rate of alcohol intake. Alcohol is directly hepatotoxic, as
are many anesthetic, chemotherapeutic, and pharmacologic agents; assessment of liver
function is advised. A liver function profile, electrolytes, blood urea nitrogen, creatinine
levels, and a urinalysis are typically sufficient to rule out intrinsic dysfunction of the
hepatobiliary tract and renal system.
Nutritional status should be maximized before treatment of patients with head and neck
cancer. Malnutrition can be identified historically with a subjective 10% loss of normal
body weight, objective diminished transferrin level, an albumin count less than 3.0/dL,
and low prealbumin levels. Deficiencies of vitamins A, C, and B
12
, riboflavin, and
thiamine are common among these patients. All deficiencies except thiamine are
considered risk factors for recurrence of squamous cell carcinoma. It is important to
ascertain whether a patient has malnutrition and is in a catabolic state. These patients are
at highest risk of impaired wound healing and postoperative pneumonia due to muscle
wasting (1,20). To prevent such complications, it is critical to establish a positive
nitrogen balance before treatment. The enteral route of alimentation is preferred.
The host performance scalethe Karnofsky scaleis used as a guide to estimate level of
impairment due to the tumor and comorbid conditions (6,7). It has been found the most
predictive indicator of postoperative complications and is critical in choosing the
appropriate treatment for a given patient (23).
PANENDOSCOPY
Operative endoscopy is performed for definitive diagnosis and to stage tumors as well as
to rule out synchronous lesions. Flexible videolaryngoscopy and biopsy sometimes can
be performed in the office. There is, however, no substitute for a thorough examination
and biopsy with the patient under general anesthesia. Operative endoscopy includes direct
laryngoscopy with or without microscopic assistance, esophagoscopy, and
tracheobronchoscopy. Complete examination of the mucous membranes of the entire
aerodigestive tract is imperative because of the fairly high incidence of synchronous
primary lesions, which varies from 5% to 15% (7,24). Retrospective studies have shown
that laryngeal lesions tend to have second primary tumors in the respiratory tract
(7,24,25). With these data, some experts argue that esophagoscopy is not necessary for
laryngeal carcinoma and that barium swallow examination should be used as a screening
tool (7,25).
Regardless of the endoscopic method, adequate biopsy specimens of the tumor must be
taken to ensure histologic diagnosis, which sometimes requires frozen section
confirmation before the patient leaves the operating suite, especially for submucosal
lesions. If the primary lesion is not known, ipsilateral tonsillectomy is recommended
because if an occult tumor is found, postoperative surveillance and radiation ports may be
altered (26). Based on the panendoscopic results, an accurate and detailed tumor diagram
is entered in the patient's permanent record, and the tumor is staged according to the 1997
TNM classification and staging system of the American Joint Committee on Cancer (27).
METASTATIC EVALUATION
Once there is histologic confirmation of malignancy, a diligent search is begun for
metastatic disease. The presence of distant metastatic lesions is more closely correlated
with the presence of cervical nodal involvement than it is with the T stage of the primary
tumor. Patients with advanced disease are at highest risk of distant metastasis (28,29).
The lungs are the most frequent site, followed by the skeletal system, liver, and brain in
decreasing order of frequency (7). Many experts believe that every patient with cancer of
the head and neck should undergo at a minimum chest radiography in the anteroposterior
and lateral projections, liver function testing, and measurement of alkaline phosphatase
levels to screen for metastatic disease. However, one study concluded that the most
useful and cost effective evaluation for metastasis consists of CT of the thorax only (29).
If suspicion is high, CT of the abdomen and a bone scan are obtained.
TREATMENT GUIDELINES
The treatment and rehabilitation of patients with head and neck cancer require numerous
resources and a multidisciplinary approach. Each individual case is first presented at a
multidisciplinary tumor board meeting, where a treatment plan is formulated (1) (Table
99.1). Once a treatment plan is devised, it is discussed with the patient. The physician
should allow adequate time in his or her schedule to discuss the treatment plan, fully
explain the risks and benefits of and alternatives in therapy, explain the likelihood of
treatment success, and answer all questions. Because patients usually are under great
stress at this time, it is advisable to have family members present for the discussion to
reinforce the information to the patient. Seeking a second opinion should be encouraged,
and a list of surgeons should be provided to the patient on request. All these
considerations tend to increase the patient's confidence and trust in the surgeon.
The first goal of successful therapy for any head and cancer is to curtail alcohol and
tobacco use. If a patient continues to abuse tobacco and alcohol, there is a 30% to 50%
risk of locoregional recurrence and a 10% to 40% risk of development of a second
primary tumor (1,5). The patient's medical, nutritional, and psychosocial status must be
optimized before therapy. This maximizes treatment and limits therapeutic complications.
Stage I and stage II lesions can be managed with primary surgery or radiation therapy,
each achieving 80% to 100% cure rates and minimal morbidity (1). The treatment
modality chosen depends on tumor location, the surgeon's experience, resources
available, and patient preference. The advantages of surgery include the ability to fully
resect the tumor while eradicating occult and regional palpable disease in a short time.
Primary surgery also reserves radiation therapy for recurrences or second primary tumors
that develop. Radiation therapy, however, has the advantage of causing minimal
functional disturbance with a comparable rate of local control. One should not, however,
underestimate the morbidity of primary radiation.
Management of advanced stage lesions (stage III and IV) usually is multimodality
therapy (1). Tumors in these stages tend to be aggressive and can be multicentric. Large
areas of tissue have to be resected to completely clear the tumor; narrow postresection
margins often are left. These advanced lesions also tend to have regional metastasis with
extracapsular nodal spread. At most cancer centers, postoperative radiation therapy with
or without adjunctive chemotherapy has been the approach to these patients at high risk.
Preoperative chemotherapy-sensitized radiation therapy for cervical metastasis (30) and
gene therapy (31) are under investigation.
There are relatively few absolute contraindications to surgery for advanced lesions of the
head and neck. They include randomly scattered intradermal nodules that cannot be
encompassed by full-thickness resection, solid fixation to the base of the skull with
intracranial extension, and fixation to the cervical spine (1). The presence of distant
metastatic lesions is not a contraindication if control of the primary disease improves
quality of life. Relative contraindications include fixation to the common or internal
carotid artery, bone, or periosteal invasion along the base of the skull and the presence of
a clinically positive node in the root of the neck (1).
Despite our best efforts, many patients have distant metastasis. The mainstay of therapy
in these cases is palliativesystemic or intraarterial cytotoxic drug therapy. In most
instances, a low-dose, minimally toxic chemotherapeutic regimen combined with use of a
long-acting analgesic is the best form of palliative care. Attempts have been made to
resect isolated metastatic lesions of the lung. The short-term results have varied, but the
long-term survival rate is essentially unchanged (32).
POSTTREATMENT REHABILITATION
Care of patients with cancer of the head and neck does not end after successful
management of the tumor. These patients are at risk of problems with respiration, speech,
deglutition, shoulder motion, smell, vision, and hearing. The job of an experienced head
and neck surgeon is to predict preoperatively the systems at highest risk of disability,
communicate the prediction to the patient, and make arrangements for posttreatment
rehabilitation.
The goal in this phase is to restore form and function to the premorbid state or at least to
a socially acceptable level. With regard to vocal and swallowing rehabilitation, speech
and language specialists are invaluable in assisting patients with alaryngeal speech and
dysphagia. Physical therapy is essential in encouraging early postoperative walking and
in beginning neck and shoulder rehabilitation after neck dissection. Prosthodontists
provide an invaluable service in fabricating midfacial and orbital prostheses for patients
who have undergone maxillectomy or orbital exenteration procedures (1). It takes the
concerted effort of many services to rehabilitate a patient with head and neck cancer. This
cooperative effort results in shorter lengths of stay in the hospital and a decreased
incidence of postoperative depression.
LONG-TERM FOLLOW-UP
A formal postoperative examination schedule is essential for a patient with head and neck
cancer. The frequency of follow-up visits has been debated in the past. The most recent
data show that 85% of recurrences occur within 2 years, and less than 5% occur later than
3 years after original therapy. According to these findings, a patient should be examined
every 4 to 6 weeks during the first year, every 2 months intervals during the second year,
every 3 to 4 months during the third year, and every 6 months thereafter (7).
A log of the patient's weight, current medications, pertinent laboratory values, and active
medical problems is updated at each visit. Thyroid function tests are performed
biannually for patients at risk of hypothyroidism, and annual chest radiographs are
obtained to rule out distant metastases. An increased level of suspicion should be
maintained in the care of patients at high risk of locoregional recurrencethose at the
extremes of age, men, immunosuppressed patients, patients with disease in advanced T
and N stages, and patients with tumors haploid in nuclear content (7,28). Second primary
tumors are more likely to occur among patients who continue to smoke or drink, those
with primary tumors in the oropharynx or hypopharynx, those lacking the
immunoglobulin light chain marker Km (1), and those with HLA-B8, HLA-DR3, and
HLA-DQw2 (7,33,34). The use of isotretinoin helps reduce the risk of development of
second primary tumors (35,36).
SUMMARY
The treatment of patients with head and neck cancer, although rewarding, is often
complex and frustrating. It requires diligence on the part of the head and neck surgeon
and the organized, cooperative effort of many specialties. This effort begins at the first
office visit and continues for the patient's life.

HIGHLIGHTS
Complete care of a patient with head and neck cancer is
directed by the surgeon, who coordinates a multidisciplinary
team that addresses medical, surgical, psychiatric, and
rehabilitation issues.
Management goals range from symptomatic relief or palliation
to full control and cure of local and regional disease. Care must
be provided while an attempt is made to maintain maximal
oropharyngeal function and an acceptable appearance.
Cancer of the head and neck is clinically staged according to
the 1997 American Joint Commission on Cancer TNM
classification and staging system. Information obtained from
the physical examination, endoscopic findings, and
radiographic studies are used for staging. In the AJCC criteria,
increases in the size or number of affected lymph nodes are
poor prognostic indicators, but the TNM system does not
account for lower-level neck nodes, fixed adenopathy, or
extracapsular spread.
Before surgery, the patient is advised to curtail all alcohol and
tobacco use or risk a 30% to 50% chance of locoregional
recurrence and a 10% to 40% chance of development of a
second primary lesion.
Preoperative correction of coagulopathy, anemia, compromised
pulmonary function, and negative protein balance reduces
postoperative complications.
There are a few absolute contraindications to surgery for
metastatic neck disease. They include the presence of randomly
scattered intradermal nodules that cannot be encompassed by
full-thickness resection, solid fixation to the skull base with
intracranial extension, and fixation to the cervical spine.
Relative contraindications include fixation to the common
internal carotid artery, bone or periosteal invasion along the
skull base, or a clinically positive lymph node low in the neck.
Early data suggest that replacing the carotid artery is safe and
efficacious.
The patients at greatest risk of distant metastasis are those with
extensive cervical metastasis, especially at multiple levels.
These patients at high risk may benefit from adjunctive or
maintenance chemotherapy after surgery and radiation therapy.
A postoperative rehabilitation program addresses problems in
breathing, speaking, swallowing, chewing, shoulder motion,
smelling, hearing, and seeing. Development of a standardized
patient database facilitates evaluation and treatment of patients
with cancer of the head and neck.
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35. Hong WK, Lippman SM, Loretta MI, et al. Prevention of second primary tumors with isotretinoin
in squamous cell carcinoma of the head and neck. N Engl J Med 1990;323:795.
36. Geyer C, Papadimitrakopoulou V, Hong WK. Chemoprevention in head and neck cancer: basic
science and clinical application. Semin Radiat Oncol 1998;8:292301.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

100 PRINCIPLES OF CHEMOTHERAPY IN THE MANAGEMENT OF HEAD AND NECK CANCER
Head & Neck SurgeryOtolaryngology
100




PRINCIPLES OF CHEMOTHERAPY IN THE
MANAGEMENT OF HEAD AND NECK CANCER
BRUCE E. BROCKSTEIN
EVERETT E. VOKES

B.E. Brockstein: Department of Medicine, Evanston Northwestern Healthcare, Evanston, Illinois.
E.E. Vokes: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago,
Illinois.


Role of the Otolaryngologist
Clinical Trials
Phase I Trials
Phase II Trials
Phase III Trials
Roles of Chemotherapy in Head and Neck Cancer
Standard Chemotherapy for Recurrent or Metastatic Cancer
Methotrexate
Cisplatin
5-Fluorouracil
Paclitaxel and Docetaxel
Other Drugs
Combination Chemotherapy
Other Roles of Chemotherapy
Unresectable Head and Neck Cancer
Postoperative Adjuvant Chemoradiation Therapy
Resectable Cancer of the Head and Neck
Induction (Neoadjuvant) Chemotherapy
Nasopharyngeal Cancer
Chemotherapy Emergencies
New Horizons
Chapter References
The use of chemotherapy to manage malignant disease is aimed at eradication of
systemic cancer or an increase in locoregional control when used with surgery or
radiation therapy. Patients are treated with chemotherapy for either macroscopic or
microscopic metastasis or to help in the management of localized tumors. Patients with
macroscopic metastasis have clinical or radiologic evidence of tumor spread. This is
commonly called metastatic disease. Microscopic metastasis implies that clinically
unrecognizable small metastatic tumor deposits are present. If the patient is not treated
the deposits become macroscopic. It is in this setting that adjuvant or neoadjuvant
chemotherapy is used.
In practice, cure has been realized for only a few types of metastatic malignant tumors.
Most patients with metastatic solid tumors cannot be treated with curative intent.
Chemotherapy as a single modality can cure patients with testicular cancer, small-cell
lung cancer, ovarian cancer, lymphoma, leukemia, and sarcomas of childhood or young
adulthood. In the microscopic, or adjuvant setting, chemotherapy is effective for breast
cancer, colon cancer, osteosarcoma, and many solid tumors of childhood. Chemotherapy
also is important in combination with radiation therapy for head and neck cancer and
other intermediate-stage solid tumors.
The relative success of chemotherapy depends on the tumor burden, the percentage of
tumor cells in a chemotherapy-responsive phase of the cell cycle, and the number of cells
with inherent or acquired resistance to chemotherapeutic agents (1). An effective
chemotherapeutic drug must be toxic more to the tumor than to normal tissue. Classic
chemotherapeutic drugs can be classified into several broad categories according to chief
mechanism of action (1). Alkylating agents cross-link DNA and interfere with DNA
replication. Among these are nitrogen mustard, cyclophosphamide, and chlorambucil.
Cisplatin and several other drugs, including the antitumor antibiotics doxorubicin,
bleomycin, and mitomycin C, also act by binding to DNA. Antimetabolites actively
interfere with cellular metabolism, frequently by means of inhibiting one or more target
enzymes. Many agents with activity in head and neck cancer fall into this group,
including methotrexate, 5-fluorouracil (5-FU), hydroxyurea, and gemcitabine. The
naturally occurring vinca alkaloids, including vincristine, vinblastine, and vinorelbine,
interfere with mitotic spindle formation. The taxanes include paclitaxel and docetaxol.
They are plant derivatives but stabilize microtubules and render them incapable of
mitosis. Another new class of drugs, topoisomerase I inhibitors, including irinotecan and
topotecan, prevent the unwinding of and therefore replication of DNA. Hormones are
frequently used in systemic therapy for malignant disease, although no role has been
established for them in treating patients with head and neck cancer. Biologic response
modifiers, including interferons and interleukins, have a role in renal cell carcinoma,
melanoma, and some forms of leukemia and lymphoma. Gene therapy is under active
investigation. Numerous systemic agents with novel mechanisms of action also are under
clinical investigation as therapy for solid tumors.
Chemotherapeutic agents often are more effective if used in combination. In selection of
appropriate drugs for a combination to manage a given disease, drugs with documented
single-agent activity usually are chosen. The ideal drugs have spectra of toxicity that do
not overlap. Scheduling of administration of the drugs take into account possible
pharmacologic interactions. Prescribing chemotherapy requires a detailed knowledge of
the pharmacology, mechanism of action, general and organ-specific toxicity, and
spectrum of activity of a drug.
ROLE OF THE OTOLARYNGOLOGIST
An otolaryngologist frequently is asked to help prevent or control the side effects of
chemotherapy or the complications of cancer. Oral effects are common. Chemotherapy-
induced mucositis must be differentiated from infection with bacteria, candida, or viruses
such as herpes or cytomegalovirus. Dental caries can cause tooth abscesses in a
neutropenic patient. Tonsillar or retropharyngeal abscesses also can occur. Chemotherapy
commonly causes dysgeusia, which is extremely disturbing to patients. Stridor and
airway obstruction can be caused by local tumor, radiation-induced edema, or allergic
reactions to chemo-therapeutic drugs derived from natural products.
CLINICAL TRIALS
Antitumor drugs and new treatment approaches are tested in several phases of clinical
trials before they are accepted or rejected. Whenever possible, chemotherapy is
administered as part of a carefully designed clinical trial with clearly stated research
goals that follow established guidelines and methods (1).
Phase I Trials
In phase I trials with human participants, tolerance and the pharmacologic properties of
newly developed compounds are studied. The end point of these studies is determination
of the maximally tolerated dose and the spectrum of toxicity among humans for a given
schedule of drug administration. Cohorts of three to six patients are treated with
escalating doses of a drug, usually starting with one tenth the dose that was lethal to one
tenth of the mice treated in animal experiments. The dose is increased until the
maximally tolerated dose, usually defined as the dose at which one third or fewer of the
patients have severe toxic reactions, is reached. New drugs or combinations of known
drugs not previously used in combination can be studied in this setting. Because the
primary end point of these trials is the maximally tolerated dose, patients with a variety of
tumor types are eligible if no standard therapy with a defined chance for attaining cure or
response exists. Although determination of toxicity is the primary scientific end point of
the trial, the clinical intent in treating the patient is tumor shrinkage and palliation of
symptoms.
Phase II Trials
In phase II trials, investigators attempt to determine the therapeutic activity, or efficacy,
of a new drug in a specific disease and stage at a defined dose or to determine the activity
of a combination of drugs at defined doses. Examples include use of a new agent to treat
patients with recurrent or metastatic cancer of the head and neck or use of a combination
of drugs before surgery or with radiation therapy. The end point is definition of activity,
measured as response rate, at an acceptable rate of toxicity.
In assessing response rates, it is important to follow carefully defined response criteria. A
complete response is defined as complete disappearance of all clinically detectable
disease. Complete disappearance of microscopic disease at surgery or biopsy is called a
histologically complete response. A partial response is defined as 50% or greater
reduction in average tumor size, measured by means of multiplying the two largest
perpendicular dimensions. Complete or partial responses must last a minimum of 28 days
to be considered clinically meaningful. Stable disease is defined as any reduction in
average tumor size of less than 50%. Progressive disease is defined as appearance of new
lesions or a 25% or greater increase in the size of known lesions. The overall response
rate for a new drug or drug combination includes all patients achieving complete or
partial responses and is expressed as a percentage of all patients entered in the trial.
A particularly difficult problem is determination of response among patients with cancer
of the head and neck undergoing multimodality treatment with chemotherapy, radiation
therapy, and surgery. Edema and fibrosis can be difficult to differentiate clinically and
radiologically from tumor. Thus biopsy proof of complete response may be necessary
both for clinical decision making and responsible reporting of the results of clinical trials.
Phase III Trials
If the information learned in a phase II trial suggests that the new drug or combination
has antitumor activity, the drug can be compared with the current standard therapy in a
phase III trial. In a phase III trial, two therapies are compared in a randomized manner.
Therapeutic activity and toxicity can be end points. For example, a new treatment with
similar activity but less toxicity is considered superior. Survival is the most commonly
and appropriately chosen end point for a phase III trial. Because large numbers of
patients are needed to detect a statistically significant difference in survival rate, these
studies are commonly conducted by more than one institution.
Phase III trials are difficult to conduct for head and neck cancer because of the relatively
low incidence of these tumors, their anatomic heterogeneity, and differences in standard
surgical and radiotherapeutic approaches at different institutions. The use of survival rate
as the end point is complicated by the older age of many patients at diagnosis and by the
high incidence of complicating medical events and second malignant lesions, both of
which often are the result of substance abuse. As a result, the terms disease-free survival
and disease-specific survival rate can be substituted for overall survival rate.
To offset accrual problems due to the relatively low incidence of disease, most
chemotherapy trials of the management of head and neck cancer are not site-specific
inquiries, although most limit eligibility to patients who have squamous cell histologic
features. This approach is valid, because differences in response rates between most sites
in the head and neck (with the exception of nasopharyngeal cancer) have not been
consistently demonstrated.
Several prognostic factors affect trial design and results (2,3). In general, the more
previous therapy a patient has received, the less likely is he or she to respond to another
therapy. Extent of disease and size of the largest mass influence response rates. A small
N1 lymph node is more likely to respond than is a large N3 lymph node. Pretreatment
performance status, a measure of functional activity, is another important prognostic
factor. These prognostic factors should be reported in published trials.
ROLES OF CHEMOTHERAPY IN HEAD AND NECK CANCER
Approximately one third of patients with squamous cell carcinoma of the head and neck
come to medical attention with highly confined, early-stage lesions. These patients need
no chemotherapy. For all other patients, chemotherapy may have a role. For the few
patients with metastatic disease and for those with locoregional recurrences that cannot
be managed with further surgery or radiation, chemotherapy has a palliative role.
Approximately one third of patients in this setting have tumor shrinkage (a partial or
complete response), which lasts an average of 3 to 6 months. For patients with
locoregionally advanced stage III and IV cancer, chemotherapy has two main roles
improving survival and organ preservation. Patients with un-resectable head and neck
cancer who receive concurrent chemotherapy and radiation rather than radiation alone
have had improved survival rates. For patients with resectable ad-vanced tumors of the
larynx and hypopharynx, chemotherapy followed by radiation has been associated with
laryngeal preservation among two thirds of patients without decreasing survival rate.
Concurrent chemoradiation therapy also may allow organ preservation with a survival
rate equivalent to that of surgery.
STANDARD CHEMOTHERAPY FOR RECURRENT OR
METASTATIC CANCER
Several drugs have been shown to have reproducible single-agent activity in the
management of metastatic or locoregionally recurrent head and neck cancer (3,4) (Table
100.1). These agents generate response rates of 30% or less with responses that are
almost exclusively partial and of short duration (2 to 6 months). Responding patients
have had longer survival times than nonresponding patients, although this may imply
selection by chemotherapy response of favorable patients rather than benefit from the
chemotherapy. Results of one randomized trial comparing chemotherapy to no
chemotherapy (supportive care only) showed a statistically significant increase in
survival rate among patients who underwent chemotherapy (5). Most other trials have
shown no survival benefit. Cure is not achieved with chemotherapy alone, with the
occasional exception of meta-static nasopharyngeal carcinoma. The primary goal of
therapy in this setting is palliation of symptoms, including pain, disfigurement by a mass,
or decreased organ function due to invasive cancer. From the perspective of clinical
research, trials with these patients are performed to identify new drugs or combinations of
drugs with antitumor activity.

TABLE 100.1. ACTIVE CHEMOTHERAPY DRUGS
FOR UNCONTROLLED METASTATIC OR
RECURRENT HEAD AND NECK CANCER WHEN
THE PATIENT HAS HAD NO PREVIOUS
CHEMOTHERAPY



Methotrexate
Methotrexate is an antimetabolite that interferes with intracellular folate metabolism by
binding to the enzyme dihydrofolate reductase. This inhibits conversion of folic acid to
tetrahydrofolate. The result is cellular depletion of reduced folates and inhibition of DNA
synthesis. This drug is active only during the S phase of the cell cycle. It selectively
affects tissues with more rapid cell turnover. The side effects of methotrexate can be
minimized by means of supplying reduced folates in the form of leucovorin within 36
hours after exposure to the drug. As a single agent, methotrexate usually is given in
weekly doses of 40 to 50 mg/m
2
. Higher doses, including an intermediate dose of 200 to
500 mg/m
2
and high-dose regimens of 1 g/m
2
or more, also can be administered. These
necessitate leucovorin rescue therapy within 36 hours. Toxic reactions include
myelosuppression, mucositis, dermatitis, nausea, vomiting, diarrhea, and hepatic fibrosis.
These toxicities are exacerbated with high-dose regimens unless leucovorin rescue is
administered. Renal injury occurs with high-dose schedules. It can be prevented with
urinary alkalinization and vigorous hydration.
Methotrexate produces a partial response rate of approximately 10% (5,6); the response
duration ranges from 1 to 6 months. Improved response and survival rates are not
consistently achieved with high-dose methotrexate regimens, but toxicity increases.
Therefore high-dose methotrexate is not used. Although single-agent methotrexate
sometimes is used, other drugs or combinations, especially those containing 5-FU or
paclitaxel or cisplatin lead to higher response rates. Survival rate is not clearly improved
with these combinations, and toxic-ity can be greater than that of single-agent therapy.
Thus methotrexate is the minimum standard treatment of patients undergoing
chemotherapy (4). It is sometimes still used as a control arm in randomized trials.
Cisplatin
Cisplatin frequently is used to manage cancer of the head and neck. Its antitumor activity
results from intracellular binding of the activated, positively charged form with a
nucleophilic site on DNA to form bifunctional covalent links that interfere with normal
DNA function (1). Cisplatin usually is administered over 2 to 6 hours in daily doses of 60
to 120 mg/m
2
, with similar efficacy reported for this entire dosage range. Renal toxicity is
common and includes mild to moderate azotemia and electrolyte wasting, particularly of
magnesium and potassium. Other toxic reactions include nausea and vomiting, peripheral
neurotoxicity, ototoxicity, and cumulative myelosuppression if several cycles of the drug
are administered. For single-agent doses ranging from 60 to 120 mg/m
2
given every 3 to 4
weeks, partial response rates of approximately 15% to 30% are achieved (6,7).
In three randomized trials, investigators compared single-agent cisplatin with single-
agent methotrexate (4). In general, no significant differences in response rates or survival
rate were found in any trial, although the overall trend in survival and response favored
cisplatin. The improvements may come at the expense of added toxicity; therefore
cisplatin is not necessarily considered superior (4).
Because of the toxicity of cisplatin, in particular its dose-limiting nephrotoxicity and
neurotoxicity, analogues of the drug have been developed with the goal of preserving the
antitumor activity of the drug and decreasing its toxic effects. Carboplatin has decreased
nephrotoxicity and neurotoxicity. Its dose-limiting toxicity is myelosuppression. Another
advantage of this compound is a comparable ease of administration. Because nausea and
vomiting are reduced, carboplatin can be given easily on an outpatient basis and without
vigorous hydration. It is active against cancer of the head and neck, but slightly less so
than is cisplatin. Carboplatin is now commonly used, particularly in the palliative setting,
in which minimizing side effects and hospital time is essential (8).
5-Fluorouracil
5-Fluorouracil is an S phasespecific uracil analogue that can be activated with two
major intracellular pathways: (a) sequential phosphorylation and incorporation into RNA
or (b) activation to 5-fluorodeoxyuridine monophosphate, which blocks the enzyme
thymidylate synthase and blocks conversion of uridine into thymidine compounds. Cells
are depleted of thymidine and cannot synthesize DNA. Many other drugs have been
shown to interact with 5-FU, and trials aimed at increasing its activity by means of
modulating its intracellular metabolism have been conducted. The most important side
effects are myelosuppression, mucositis, dermatitis, diarrhea, and cardiac toxicity. Used
as a single-agent intravenous bolus to treat patients with head and neck cancer, 5-FU has
limited activity. A response rate of 13% was found in one large, randomized trial (7). 5-
Fluorouracil may be substantially more active administered in a 5-day continuous
infusion and clearly adds to the response rate of cisplatin.
Paclitaxel and Docetaxel
Paclitaxel and docetaxel are among the most active drugs against head and neck cancer
(6). Paclitaxel was initially isolated from the bark of the Pacific yew tree, although it is
now produced synthetically. The taxanes stabilize tubulin polymers and prevent cell
division. A cooperative group phase II study of single-agent paclitaxel given at fairly
high doses over 24 hours to 30 patients had a response rate of 40% (9), although the drug
usually is given as a 3-hour outpatient infusion. The true response rate is likely less than
this. Larger studies of paclitaxel with cisplatin have yielded response rates of only 35%
(10).
Other Drugs
Several other drugs have had a moderate degree of activity in the management of head
and neck cancer. Bleomycin, a naturally occurring antitumor antibiotic, was often used in
combination with cisplatin or methotrexate. The risk of fatal interstitial pneumonitis
limits cumulative use of this agent, and the development of other drugs has limited its
usefulness. Ifosfamide, an alkylating agent closely related to cyclophosphamide, has
single-agent activity and has been tested in several combination regimens. Other active
drugs are listed in Table 100.1.
COMBINATION CHEMOTHERAPY
Combinations of drugs are thought to be superior to single agents because cells resistant
to one agent may be sensitive to another. In the management of head and neck cancer,
most combinations have been based on methotrexate or cisplatin. Several randomized
studies have compared a single agent with a combination regimen. In these studies,
investigators attempted to increase response rates by combining drugs with proven
single-agent activity, such as cisplatin, methotrexate, and bleomycin. In other studies,
investigators attempted to use active drugs that might interact synergistically with each
other, for which the observed cell destruction would exceed that expected from the sum
of the activity of both agents. This may be the case for the combination of cisplatin and 5-
FU, which is synergistic in vitro (11). Clinically, administration of cisplatin followed by a
4- to 5-day continuous intravenous infusion of 5-FU has been an active combination. In
the care of patients with recurrent disease, it has had reproducible response rates ranging
from 30% to 40% (7,8). In the neoadjuvant setting of locally advanced, nonmetastatic
disease, impressive response rates of about 80%, with 10% to 40% complete responses,
have occurred (3,6,12,13). The combination of cisplatin and 5-FU was compared with
each of these drugs delivered as single agents in a three-arm randomized trial (7).
Although the response rate of the combination (32%) was significantly higher than that of
cisplatin alone (17%) or 5-FU alone (13%), there was no significant difference in the
median survival period of 5 to 6 months for all groups. In a three-armed, randomized
trial, the Southwestern Oncology Group (8) compared cisplatin and 5-FU with a
combination of carboplatin and 5-FU (postulated to be equally active but less toxic) and
single-agent methotrexate as standard therapy. Both cisplatin and carboplatin combined
with infusion of 5-FU had a better response rate than did methotrexate alone. Both
combinations were more toxic, and survival rate was not affected.
The taxanes are commonly used in combination regimens. Results of a recently
completed trial should identify whether cisplatin plus 5-fluorouracil or cisplatin plus
paclitaxel is a more active regimen for recurrent and metastatic head and neck cancer
(8b). Several other three-drug or four-drug combination regimens containing taxanes
have shown high response rates and are under development. An analysis of the available,
appropriately conducted, randomized chemotherapy trials had the following conclusions
about combination regimens (4):
Combinations produce statistically significantly higher re-sponse rates than do
single agents, including methotrexate.
Cisplatin and infusional 5-FU produce higher response rates than do single agents
or other combinations.
In no comparison group (single agent or combinations with taxanes excluded) is
survival time meaningfully lengthened.
The toxicities of cisplatin and infusional 5-FU, especially nausea and vomiting,
are significantly greater than those of single agents.
Clinical research now focuses on identification of new agents and combinations with
activity against cancer of the head and neck. In particular, the new agents paclitaxel,
docetaxel, irinotecan, topotecan, and gemcitabine have only begun to be tested in
combinations for cancer of the head and neck, although reports of combinations, in
particular paclitaxel and cisplatin or carboplatin, appear encouraging. Drugs with novel
mechanisms, such as angiogenesis inhibitors and other inhibitors of invasion and
metastasis, are under investigation. The role of retinoids, selenium, and other molecules
in the reversal of premalignant lesions and prevention of primary or second malignant
tumors also is under investigation (3).
In summary, chemotherapy for recurrent or metastatic cancer head and neck is palliative
for some patients, although the effect on survival rate is small. Methotrexate in weekly
low doses, cisplatin, infusional 5-FU, paclitaxel and docetaxel are the most active single
agents. The response rate is 20% to 30% and the response lasts for 1 to 6 months.
Combination chemotherapy, particularly cisplatin with 5-FU and cisplatin with
paclitaxel, produces higher response rates, although long-term survival rarely is achieved.
Because cure with result of any of these drugs or combinations is unlikely among patients
previously treated, and in view of the poor outcome with standard single agents and
combinations, patients should be treated in a clinical trial whenever possible.
OTHER ROLES OF CHEMOTHERAPY
In concomitant chemoradiation therapy, chemotherapy and radiation therapy are used
simultaneously or in a rapidly alternating sequence. Chemotherapy can increase the
efficacy of radiation therapy within the radiation treatment field. The possible
mechanisms underlying this effect are summarized in Table 100.2. Because head and
neck cancer manifests predominantly as a locoregional disease, concomitant
chemoradiation therapy is valuable because it focuses on the site that determines
prognosis. The early use of chemotherapy also can sterilize distant micrometastasis.

TABLE 100.2. BENEFITS AND MECHANISMS OF
CHEMORADIOTHERAPY



Chemoradiation therapy can be used in several settings. For unresectable locoregionally
advanced cancer of the head and neck, chemoradiation therapy is clearly better than
radiation therapy alone in most settings. In the postoperative setting, results of several
studies suggest that chemoradiation therapy in the treatment of patients at high risk is
better than radiation therapy alone. For patients with resectable disease who are to
undergo radiation therapy alone for medical reasons or because they refuse surgical
treatment, chemoradiation therapy is generally superior to radiation therapy alone.
Chemoradiation therapy has not been compared directly with surgery and radiation
therapy for resectable disease. Comparison of results of phase II studies suggests,
however, that appropriately administered intensive chemoradiation therapy can be at least
equivalent to surgery plus radiation therapy for medically fit patients. Representative
randomized studies in which cisplatin or carboplatin with or without 5-FU was used
concomitantly with chemotherapy are detailed in Table 100.3.

TABLE 100.3. REPRESENTATIVE STUDIES OF
CONCOMITANT CHEMOTHERAPY AND
RADIATION THERAPY VERSUS RADIATION
THERAPY ALONE



Unresectable Head and Neck Cancer
The definition of resectability is variable and is highly dependent on surgical and patient
choice. This is an important factor in interpreting the outcomes of trials involving patients
with unresectable cancer of the head and neck. Nonetheless, the long-term survival rate
with radiation therapy alone for unresectable cancer of the head and neck historically has
been 10% to 30%. Numerous trials have been performed over the last two to three
decades in which patients with unresectable cancer of the head and neck have been
randomized to undergo radiation therapy alone or radiation therapy with concomitant
chemotherapy. Many drugs have been used alone or in combination with different
strategies regarding factors such as timing of chemotherapy and dose of radiation.
General conclusions can be drawn from these studies, particularly from three recent,
large-scale metaanalyses. In general, with most single-agent chemotherapeutic drugs
given concomitantly with chemotherapy, locoregional control and survival are better than
with radiation therapy alone.
Direct comparisons have not been made between radiosensitizing chemotherapeutic
drugs. The most frequently used, and perhaps best single-agent chemotherapeutic drugs,
are 5-FU and cisplatin. Although they have not been directly compared with radiation
therapy alone, paclitaxel and docetaxel also are commonly used. Several other drugs are
effective but are less commonly used because of concerns about side effects or decreases
in efficacy. Many combination regimens have been used, the most effective of which
appears to be the combination of cisplatin and 5-FU. The combination of carboplatin and
taxol is undergoing rigorous study owing to its potential efficacy and relative tolerability.
The combination of 5-FU and hydroxyurea has been extensively studied at the University
of Chicago, and appears to be a synergistic regimen that may be as effective or more
effective than cisplatin with 5-FU.
The results of the three aforementioned metaanalyses have mostly involved patients with
unresectable lesions. El-Sayed and Nelson (14) analyzed 11 studies of concomitant
chemoradiation therapy that had adequate survival data and found a 22% relative
reduction in the hazard of death (95% confidence interval [CI], 8%33%; P < .005). In a
metaanalysis of 16 trials, Munro (15) found an absolute benefit of 12% (95% CI, 5%
19%). The Meta-analysis of Chemotherapy on Head and Neck Cancer Collaborative
Group (MACH-NC) performed an individual patient metaanalysis involving more than
10,000 patients in total. The hazard ratio of death among the concomitant group was 0.81
(95% CI, 0.760.88). This represented an improvement in 5-year survival rate from 32%
to 40%. The subset of trials in which multiagent chemotherapy was used showed a hazard
ratio of 0.69 (16).
The benefit of chemoradiation therapy must be weighed against the toxicity inherent in
its use. The risk of acute mucositis, dermatitis, and chemotherapy-specific side effects is
greater than with either mode of therapy alone. Short-term use of gastric feeding devices
is needed more frequently, and although few data exist, pharyngeal dysfunction may be
more common with chemoradiation therapy. The latest generation of studies continues to
show has shown improved survival rates with aggressive chemoradiation therapy. This
advantage is maintained even when chemotherapy is added to hyperfractionated radiation
therapy, so the benefit of chemotherapy is due not solely to more intensive treatment
(hyperfractionation) but to a true radioenhancing effect (17,18).
Postoperative Adjuvant Chemoradiation Therapy
Only a few studies have specifically assessed postoperative use of chemoradiation
therapy versus radiation therapy alone. In one study of 83 patients with stage III or IV
cancer of the head and neck with extracapsular lymph node spread, patients were treated
with radiation therapy alone or with weekly administration of cisplatin. The combined
modality group had both improved locoregional control and an improved overall survival
rate (36% as opposed to 13% 5-year overall survival rate, P < .01) (19). In a trial from
Yale University (20), more than 200 patients were treated with radiation therapy or
radiation therapy plus mitomycin. Sixty percent were treated postoperatively. The
combined-modality group had better locoregional control and a better cause-specific
survival rate than did those who underwent radiation therapy alone. The accrual stages of
other studies are being completed, and the results will be published in the next few years.
Resectable Cancer of the Head and Neck
Until quite recently, chemoradiation therapy has had a lesser role in the management of
resectable cancer of the head and neck. It is becoming evident that at least some intensive
chemoradiation therapy programs used to treat patients who are medically fit can yield
results that appear to be comparable with and in some cases better than those of surgery
plus radiation therapy. As of this writing, however, this concept has not yet gained
widespread acceptance. Even when primary-site surgery is not initially used, the head and
neck surgeon still has an important role in diagnostic procedures, follow-up evaluation,
neck dissection for some patients, and surgical salvage when chemoradiation therapy
fails.
No randomized data have been analyzed to compare the results of chemoradiation
therapy with surgery with or without radiation therapy. Results of several indirect
comparisons suggest chemoradiation therapy can be an alternative to surgery. Adelstein
et al. (21) randomized 100 patients, mostly with stage IV disease, to undergo radiation
therapy alone or radiation therapy with concomitant cisplatin and 5-FU administration
during weeks 1 and 4 of radiation therapy. In the chemoradiation therapy arm, the 5-year
survival rate was 50%. Eleven patients needed surgical salvage, and 8 underwent
successful procedures. The overall survival rate with primary site preservation was 42%.
Although the survival rate was equivalent in the radiation therapy only arm, 27 patients
needed surgical salvage, which was successful for 17 patients. Brizel et al. (17)
randomized 116 patients to receive hyperfractionated radiation therapy alone or to
receive chemotherapy (cisplatin and 5-FU) plus hyperfractionated radiation therapy. The
3-year survival rate was 55% in the chemoradiation therapy arm. This percentage is
comparable with that achieved in most surgical series. Although the survival rate among
the patients with resectable disease (47% of patients) was not reported, it was likely as
good or better than that for the entire group. In a similar study, 130 patients with mostly
stage IV disease underwent hyperfractionated radiation therapy with or without daily
administration of cisplatin. Forty-seven percent of the patients who underwent
chemoradiation therapy had resectable lesions and likely had an overall survival rate
better than the 46% 5-year survival for the entire group (22).
Several phase II trials also have examined the issue of chemoradiation therapy for
resectable disease. Kies et al. (23) administered three cycles of induction chemotherapy
of cisplatin, 5-FU, leucovorin, and interferon- followed by chemoradiation therapy with
5-FU, hydroxyurea, and radiation therapy (FHX) to 93 patients with stage IV cancer of
the head and neck. Although not specifically reported, a large number of patients had
potentially resectable disease. The 5-year survival rate for the entire group was 62%.
Because patients with resectable disease usually have less biologically aggressive
disease, it is likely that the patients with resectable disease not specifically described had
an even better survival rate. Several other studies have yielded similar results (24,25). We
believe that patients with stage III or IV resectable disease who are likely to have
functional or cosmetic sequelae of the surgery and who need postoperative radiation
therapy should be offered an aggressive chemoradiation therapy regimen if they are
medically able.
Induction (Neoadjuvant) Chemotherapy
Neoadjuvant chemotherapy has been a frequently investigated concept in cancer of the
head and neck. The rationale for this mode of therapy is summarized in Table 100.4.
Most important among the reasons for using chemotherapy earlier in the course of
disease is lowering the systemic tumor cell burden at a time when fewer chemotherapy-
resistant cells exist. The regional vasculature is intact, and drug delivery to the tumor may
be better. Surgery and radiation therapy may be more likely to be successful if used
against a smaller tumor (downsizing). These theoretic advantages are offset by the
disadvantages of increased toxicity, duration, and cost of overall treatment. More
important, it has been postulated that cells that survive chemotherapy may not respond to
subsequent radiation therapy. In the rare event of disease progression during
chemotherapy, a resectable tumor may become unresectable, and the chance for cure is
lost. The practical reasons for investigating or using neoadjuvant chemotherapy are to
attempt to improve the likelihood of organ preservation or cure.

TABLE 100.4. ADVANTAGES AND
DISADVANTAGES OF INDUCTION
CHEMOTHERAPY FOR LOCALLY ADVANCED
HEAD AND NECK CANCER



Clinical trials of neoadjuvant chemotherapy have been performed for 20 years. In pilot
studies, investigators cautiously administered single agents for one or two cycles before
administering local therapy. Use of two-drug and three-drug combinations for two to
three cycles eventually became a common approach (3,26). These combinations were
based on drugs with single-agent activity (see earlier). The most extensively used and
studied combination is a regimen of cisplatin and 5-FU, although others have been used
with similar but less consistent efficacy. From these phase II and phase III studies (Table
100.5), the following general conclusions can be made:

TABLE 100.5. RANDOMIZED TRIALS OF
NEOADJUVANT CHEMOTHERAPY



Overall response rates exceeding 80% are frequently achieved.
Complete response rates usually range from 20% to 50%, most trials showing
approximately 30%. Some of the clinical complete responses are confirmed
histologically at surgery.
Toxicity usually is moderate to severe, but administration of subsequent standard
local therapy is not compromised, although a small percentage of patients with
complete re-sponses refuse subsequent planned local therapy.
Patients achieving complete responses have a better prognosis, particularly if the
responses are confirmed histologically.
Organ preservation is possible, at least in laryngeal and hypopharyngeal
carcinoma.
Survival, assessed in randomized studies, generally does not improve.
The last observation was made by analyzing results of randomized trials in which
standard local therapy (surgery followed by radiation therapy) was compared with the
best neoadjuvant chemotherapy (three cycles of an active regimen that produced
complete response rates greater than 20% and overall response rates greater than 80%)
followed by the same local therapy. Because various anatomic sites and other prognostic
factors, including performance status and T and N stages of disease, must be accounted
for, a large number of patients must be accrued for detection of a statistically significant
difference in survival rate, such as more than 10% to 20% after 2 to 3 years of follow-up
study.
A large number of randomized trials comparing neoadjuvant chemotherapy before local
therapy with local therapy alone have been conducted. Most had too few subjects or were
too poorly designed to be conclusive. In approximately 10 studies, however, large
numbers of patients were enrolled. The most important of these are summarized in Table
100.5 (12,13,27,28.29 and 30), and a complete description has been summarized
elsewhere (26). In none of the 10 studies was overall survival time prolonged. All seven
studies that found distant metastasis a site of first failure showed a decrease among the
patients receiving chemotherapy. Most patients died of complications of locoregional
disease; therefore the decreased rate of distant metastasis did not translate into a survival
benefit. These negative results were confirmed in three metaanalyses (14,15 and 16). In
the individual patient metaanalysis performed by the MACH-NC, the patients receiving
neoadjuvant cisplatin plus 5-FU has a statistically significant survival benefit (hazard
ratio, 0.88; 95% CI, 0.790.97). Because metastatic lesions decrease with neoadjuvant
chemotherapy, it is possible that with improved locoregional treatment, neoadjuvant
chemotherapy may improve survival rates.
Two studies that pursued organ preservation as a clinical goal deserve special mention.
One is the randomized trial conducted by the Department of Veterans Affairs Laryngeal
Cancer Study Group (12). In this study, patients with advanced laryngeal cancer were
randomized to undergo standard therapy with surgery and postoperative radiation therapy
or to receive three cycles of neoadjuvant cisplatin and 5-FU followed by radiation
therapy. Response was assessed after two cycles of chemotherapy. Patients with partial or
complete responses continued with a third cycle of chemotherapy. Only patients who did
not respond to the first two cycles of chemotherapy or had residual disease after radiation
therapy proceeded with surgery in the experimental study arm. Two goals were pursued
in this studyimproved survival and preservation of the larynx. The 2-year actuarial
rates of overall survival were identical in the two groups68%. The most important
finding was the high rate of preservation of the larynx. Sixty-four percent of patients in
the chemotherapy arm had their larynxes preserved; the median follow-up period was 33
months. Thirty-nine percent of patients continued to be free of disease and had an intact
larynx. Only two salvage laryngectomies were performed after the first year. A similar
rate of disease-free survival with laryngeal preservation (28%) was achieved in another
study (29) with a similar design in which the patients had hypopharyngeal cancer.
The results of these two studies show that all patients with laryngeal or hypopharyngeal
carcinoma who would otherwise undergo total laryngectomy or pharyngolaryngectomy
should be offered organ preservation therapy. The protocol used in the Veterans Affairs
larynx trial is acceptable at a minimum, although the addition of concomitant
chemotherapy to radiation therapy is likely to further improve survival and organ
preservation. In the MACH-NC metaanalysis, the inclusion of a third small study caused
an insignificant negative effect of chemotherapy, although similar outcome continued in
the two major studies. An ongoing Intergroup study is aimed at determining an optimal
strategy for preservation of the larynx. The investigators are comparing radiation therapy
alone with radiation therapy with neoadjuvant or concomitant chemotherapy.
Several new, aggressive, multiagent neoadjuvant chemotherapy regimens administered
before radiation therapy are showing promise at improving survival (23,31). Neoadjuvant
chemotherapy has not conclusively improved survival and therefore continues to be
investigational therapy for disease of sites other than the larynx and hypopharynx.
Ongoing roles include organ preservation in larynx and management of hypopharyngeal
cancer. There is a possible role in the management of nasopharyngeal cancer. The
neoadjuvant setting may be appropriate for testing chemotherapeutic agents and drug
combinations.
Nasopharyngeal Cancer
Chemotherapy is important in the management of nasopharyngeal cancer. It is considered
standard therapy for all but the few early-stage cases. The optimal timing and role of
chemotherapy have yet to be determined. Metastatic undifferentiated carcinoma, or
lymphoepithelioma, of the nasopharynx is highly sensitive to chemotherapy. In four
consecutive studies involving a total of 165 patients treated with cisplatin-containing
regimens for metastatic lymphoepithelioma, 19% achieved a complete response, and 64%
responded with at least a partial response. Twelve percent of patients were free of disease
3 years after chemotherapy, and 14 of 165 were disease free after at least 82 months (32).
Chemotherapy also has a role in the management of squamous cell carcinoma and
lymphoepithelioma when disease if local. The most compelling results are from an
Intergroup trial in the United States in which 147 patients were randomized to undergo
radiation therapy alone or radiation therapy with concomitant cisplatin and postradiation
therapy with cisplatin and 5-FU. The study was stopped early when a significant
difference in 2-year survival rate occurred in favor of the chemotherapy arm. The 3-year
survival rate for the patients who underwent chemotherapy was 78%; the 3-year survival
rate was 47% for patients who did not undergo chemotherapy (P = .005) (33). Early
follow-up results from a study with 321 patients in an endemic area of Asia confirmed
similar results (34).
CHEMOTHERAPY EMERGENCIES
Chemotherapy emergencies can be divided into those characterized by severe
symptomatic side effects or organ-specific toxicities (Table 100.6 and Table 100.7).
Emergencies particularly relevant to cancer of the head and neck drugs are discussed.
Intractable nausea, vomiting, or diarrhea, although less common with modern antiemetic
and antidiarrheal agents, still occurs among some patients. Dehydration and electrolyte
disturbances can occur, and patients may need hospitalization for administration of
antiemetics and intravenous fluids. Severe mucositis can prompt hospitalization for
administration of parenteral narcotics and hydration.

TABLE 100.6. COMPLICATIONS
CHEMOTHERAPY



TABLE 100.7. EMERGENCIES
CHEMOTHERAPY



With administration of most chemotherapeutic drugs, granulocytopenia and
thrombocytopenia regularly occur. Although granulocytopenia itself does not necessitate
hospitalization, infection, characterized by fever, chills, or specific signs and symptoms,
indicates a need for immediate hospitalization if the patient has neutropenia. Blood,
urine, and other fluids are cultured, and broad-spectrum, antipseudomonal antibiotics are
started immediately and empirically. Administration of antibiotics is continued until
neutropenia, fever, and infection resolve. Administration of granulocyte colony-
stimulating factor has a role in preventing infection among aggressively treated patients
but is not as helpful if initiated in the setting of established neutropenic fever.
Thrombocytopenia can be life-threatening, particularly if platelet counts decrease to less
than 10,000/L to 20,000/L, in which case spontaneous and fatal hemorrhage can occur.
The patient is treated with platelet transfusions until platelet count returns to normal.
These patients may need hospitalization because of bleeding or, in some instances, for
transfusions of platelets.
Acute renal failure can occur with administration of high-dose methotrexate or cisplatin.
Patients receiving cisplatin can have severe electrolyte wasting. These conditions
necessitate in-hospital evaluation and treatment by a medical oncologist and nephrologist.
Allergic reactions, especially to paclitaxel or bleomycin, can be severe and necessitate
treatment with antihistamines, steroids, and other support. Leakage or extravasation of
drugs such as vincristine or doxorubicin can cause necrosis of the skin and necessitate
immediate treatment.
NEW HORIZONS
Investigational chemotherapy for head and neck cancer has a strong rationale and must be
pursued because the results achieved with conventional therapy are not satisfactory. The
search for more active systemic therapy for cancer of the head and neck is focused on the
development of new active single agents and possible integration of these agents with
other drugs and modalities. Drugs with novel mechanisms of action are in various stages
of development. Molecular therapies are several years from success but will have a
critical role in the future. Similarly, integration of chemopreventive agents with the
multispecialty treatment of these patients is only just beginning.
Several new approaches are actively being studied for the management of incurable,
locoregionally advanced cancer of the head and neck. Photodynamic therapy involves
administration of a systemic photosensitizer that becomes preferentially incorporated into
tumor cells. An illumination source is directed locally or endoscopically near the tumor
and induces cell killing. Complete responses have occurred in small tumors, as has
shrinkage and palliation of symptoms of larger tumors.
Gene therapy for cancer of the head and neck is being actively studied. In these studies
viral vectors have been used to deliver the p53 tumor suppressor gene to tumor cells by
means of direct intratumoral injection. Both wild-type p53 (Ad-p53) and genetically
altered p53 genes have been used; the responses occurred in the tumors treated. Other
investigational therapies for locoregionally advanced, incurable tumors include injection
chemotherapy with cisplatin and chemotherapy with concomitant repetition of irradiation.
Novel systemic therapies also are being used to manage cancer of the head and neck.
Growth factor receptors and cell signaling pathways are one area actively investigated.
Epidermal growth factor receptor is overexpressed in most patients with cancer of the
head and neck. Monoclonal antibodies directed against epidermal growth factor receptor
given alone, with chemotherapy or radiation therapy, or as radioimmunoconjugates have
shown early promise and are actively being studied. As with therapy for most other
cancers, angiogenesis inhibitors aimed at preventing tumor growth or metastasis also are
being extensively studied. Although not all these therapies are likely to be successful, it is
likely that some of them will become a part of the treatment armamentarium in the near
future.

HIGHLIGHTS
Standard chemotherapy consists of methotrexate, cisplatin or
carboplatin, 5-FU, or paclitaxel or docetaxel. It is administered
to patients with symptomatic recurrent or metastatic cancer of
the head and neck. Treatment intent is palliative.
Combination chemotherapy for recurrent disease can improve
response rates but has little impact on survival rate.
Neoadjuvant chemotherapy for locoregionally advanced cancer
of the head and neck can produce high overall and complete
response rates, but its effect on survival is minimal.
Laryngeal preservation is feasible with chemotherapy, but
administration of neoadjuvant chemotherapy for other cancers
of the head and neck is confined to an investigational setting.
Concomitant chemoradiation therapy for locoregionally
advanced head and neck cancer has a sound rationale.
Randomized trials have shown moderately higher disease-free
and overall survival rates for many drugs and combinations
than obtained with single-modality radiation therapy. It is an
appropriate treatment option for patients with unresectable
disease, for some patients after surgical treatment, and for some
patients with resectable disease in the appropriate treatment
setting.
Chemotherapy has a role in management of metastatic
lymphoepithelioma. Concomitant cisplatin and radiation
therapy is included in the management of locoregionally
advanced nasopharyngeal cancer.
Because the outcome with conventional treatment of many
patients with advanced head and neck cancer is disappointing,
all patients need to be strongly encouraged to participate in
clinical trials.
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11. Scanlon KY, Newman EM, Priest DG. Biochemical basis for cisplatin and 5-fluorouracil
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13. Paccagnella A, Orlando A, Marchiori C, et al. Phase III trial of initial chemotherapy in stage III or
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J Natl Cancer Inst 1994;86:265272.
14. El-Sayed S, Nelson N. Adjuvant and adjunctive chemotherapy in the management of squamous
cell carcinoma of the head and neck region: a meta-analysis of prospective and randomized trials.
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15. Munro A. An overview of randomized controlled trials of adjuvant chemotherapy in head and
neck cancer. Br J Cancer 1995;71:8391.
16. Pignon JP, Bourhis J, Domenge C, et al. Chemotherapy added to locoregional treatment for head
and neck squamous cell carcinoma: three meta-analyses of updated individual patient data. Lancet
2000;355:949955.
17. Brizel DM, Albers ME, Fisher R, et al. Hyperfractionated irradiation with or without concurrent
chemotherapy for locally advanced head and neck cancer. N Engl J Med 1998;338:17981804.
18. Wendt TG, Grabenbauer GG, Rodel CM. Simultaneous radiotherapy versus radiotherapy alone in
advanced head and neck cancer: a randomized multicenter study. J Clin Oncol 16:13181324.
19. Bachaud JM, Cohen-Jonathan E, Alzieu C, et al. Combined postoperative radiotherapy and
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20. Haffty BG, Son YH, Papac R, et al. Chemotherapy as an adjunct to radiation in the treatment of
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21. Adelstein DJ, Lavertu P, Saxton JP, et al. Mature results of a phase III randomized trial comparing
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23. Kies MS, Haraf DJ, Athanasiadis I, et al. Induction chemotherapy followed by concurrent
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24. Vokes EE, Kies M, Haraf DJ, et al. Concomitant chemoradiotherapy as primary therapy for
locoregionally advanced head and neck cancer. J Clin Oncol 2000;18:16521661.
25. Brockstein B, Haraf DJ, Stenson K, et al. Phase I study of concomitant chemoradiotherapy with
paclitaxel, fluorouracil, and hydroxyurea with granulocyte colony stimulating factor support for
patients with poor prognosis cancer of the head and neck. J Clin Oncol 1998;16:735744.
26. Brockstein BE, Vokes EE. Chemoradiotherapy for head and neck cancer. PPO Updates
1996;10:119.
27. Final Report of the Head and Neck Contracts Program. Adjuvant chemotherapy for advanced head
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28. Laramore GB, Scott CB, Al-Sarraf M, et al. Adjuvant chemotherapy for resectable squamous cell
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1992;23:705713.
29. Lefebvre JL, Chevalier P, Luboinski B, et al. Larynx preservation in pyriform sinus cancer:
preliminary results of a European organization for research and treatment of cancer max III trial. J
Natl Cancer Inst 1996;88:890.
30. Depondt J, Gehanno P, Martin M, et al. Neoadjuvant chemotherapy with carboplatin/5-
fluorouracil in head and neck cancer. Oncology 1993;50[Suppl 2]:23.
31. Clark JR, Busse PM, Norris CM, et al. Induction chemotherapy with cisplatin, fluorouracil, and
high dose leucovorin for squamous cell carcinoma of the head and neck: long-term results. J Clin
Oncol 1997;15:31003110.
32. Fandi A, Bachouchi M, Azli N, et al. Long-term disease free survivors in metastatic
undifferentiated carcinoma of the nasopharynx type. J Clin Oncol 2000;18:13241330.
33. Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with
advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol
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34. Chan AT, Teo PM, Ngan RK, et al. A phase III randomized trial comparing concurrent
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1637.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

101 PRINCIPLES OF RADIATION ONCOLOGY
Head & Neck SurgeryOtolaryngology
101




PRINCIPLES OF RADIATION ONCOLOGY
DAVID H. HUSSEY
B-CHEN WEN

D.H. Hussey: Department of Radiation Oncology, University of Texas Health Science Center, San
Antonio, Texas.
B-C. Wen: Department of Radiology/Oncology, University of Miami College of Medicine, Miami,
Florida.


Radiation Physics
External Beam Irradiation
Brachytherapy
Radiobiology
Cell Death
Random Nature of Cell Kill
Sublethal Injury
Tumor Cell Hypoxia
Cell Cycle Effects
Repopulation
Dose-Response Relations
Regression Rates
Treatment
Selection of Treatment Modality
Radiation Therapy Alone
Combined Surgery and Radiation Therapy
Preoperative Radiation Therapy
Postoperative Radiation Therapy
Complications
Acute Tissue Reactions
Late Tissue Reactions
Chapter References
Radiation oncology, as one of three arms of multidisciplinary cancer therapy, is an
important part of the management of many cancers of the head and neck. Although it is
effective as the only therapy for a variety of head and neck cancers, radiation is being
used more frequently as an adjunct to surgery or in combination with chemotherapy as a
means of preserving organ function. In this chapter the fundamental concepts of radiation
physics and biology are described as they relate to the use of radiation therapy for head
and neck cancer.
RADIATION PHYSICS
Radiation therapy is based on the interaction of ionizing particlestypically x-rays,
gamma rays, and electronswith tissues at the molecular level. This interaction depends
on the release of localized energy sufficient to break chemical bonds through the
production of secondary charged particles, usually electrons. These secondary electrons
produced by the primary beam are ultimately responsible for inflicting biologic injury
(1). Ra-diation therapy is delivered with an external beam of radiation (teleradiation
therapy) or with a radioactive implant or mold (Brachtherapy). External beam radiation
therapy entails generation of energy particles at some distance from the patient.
Brachytherapy entails placement of radioactive sources near or within a tumor.
External Beam Irradiation
Typical radiation therapy departments now have dual-energy linear accelerators capable
of generating low-energy megavoltage x-rays (4 to 6 MeV) and high-energy megavoltage
x-rays (15 to 25 MeV) along with electrons (Fig. 101.1). This range of x-ray and electron
energies allows one to tailor distribution of the radiation dose to the location of the
cancer. Most patients are treated with megavoltage x-rays or gamma rays (photons),
which are penetrating beams useful for managing a wide variety of cancers. The
characteristics of an x-ray or gamma ray beam (as opposed to electrons) important in
radiation therapy are its skin-sparing properties, its depth dose properties (penetration),
and its isodose distribution (beam uniformity). The skin-sparing and depth dose
properties of photon beams commonly used are shown in Fig. 101.1 (2).

FIGURE 101.1. Skin-sparing and depth dose properties
of x-ray and gamma ray beams commonly available in
radiation therapy departments.



Selection of beam energy is based on the location of the tumor. Cancers 12 to 15 cm
deep, such as cancer of the prostate or uterine cervix, usually are best managed with 15-
to 25-MeV x-rays because these beams are more penetrating and have better skin-sparing
properties than do lower-energy beams (Fig. 101.1). Cancer of the head and neck,
however, can be managed with 4- to 6-MeV x-rays or cobalt 60 gamma rays, at least
initially. These tumors are located no more than 7 to 8 cm deep, and there is usually a
need to treat the regional lymph nodes, which are superficial. However, 15- to 25-MeV x-
rays occasionally are used to deliver additional treatment (a boost) to certain head and
neck cancers, such as cancer of the base of the tongue or nasopharynx.
Electron beams are useful for managing superficial lesions. Unlike x-rays, electrons have
a finite range, so tissues deep to the tumor can be spared (Fig. 101.2). A guideline for the
useful range in centimeters of an electron beam is its energy in megaelectron volts (MeV)
divided by three. For cancer treatment, 6-MeV electrons are commonly used for cancers
of the skin or lip, 6- to 9-MeV electrons for cervical lymph nodes over the spinal cord, 9-
to 12-MeV electrons for cancers of the buccal mucosa, and 15- to 18-MeV electrons for
cancers of the tonsillar area or parotid gland. Electron beams have poorer skin-sparing
properties than do photon beams. This is an advantage for superficial skin lesions, but the
beams must frequently be combined with high-energy x-rays if high doses are planned to
deep tumors to avoid high doses to the surface.

FIGURE 101.2. Skin-sparing and depth dose properties
of a variety of electron beams. Electron beams have a
limited range, so they are useful for sparing tissues deep
to the target volume. A rule of thumb is that the useful
range of an electron beam in centimeters is equal to the
megaelectron volts of the beam divided by three. Electron
beams provide less skin sparing than megavoltage x-ray
and gamma ray beams.



Brachytherapy
Brachytherapy is a technique in which radioactive sources are placed within or close to
the target volume. These sources can be placed directly into the tumor and surrounding
tissues (interstitial therapy), within body cavities (intracavitary therapy), or onto
epithelial surfaces (surface molds). Brachytherapy implants can be temporary or
permanent. Temporary implants usually are long-lived isotopes, such as radium 226,
cesium 137, and iridium 192. Permanent implants are short-lived isotopes, such as gold
198, iodine 125, or palladium 103, because the radiation emitted must decay to negligible
levels in a relatively short time (2).
The advantages of brachytherapy over external beam irradiation are twofold. First, the
radiation is mainly confined to the implant volume, so a greater dose can be delivered to
the tumor with a lesser dose to adjacent normal tissues. This produces greater local tumor
control and fewer complications. Second, most brachytherapy is delivered continuously
at a low dose rate. This is theoretically more effective than intermittent high-dose-rate
administration of external beam radiation in the management of hypoxic or slowly
proliferating cancers (3). High-dose-rate temporary brachytherapy has become more
popular because it allows shorter treatment times.
Brachytherapy implants are effective only if the entire tumor volume is involved. The
tumor must be accessible and relatively well demarcated. Large or poorly defined cancers
usually are not irradiated with brachytherapeutic techniques because it is difficult to reach
peripheral extensions of the cancer with the implant. Brachytherapy also is not used as
the only treatment modality if there is high risk of regional lymph node metastasis. The
isotopes commonly used for brachytherapy are listed in Table 101.1. If the implant is
used as the sole treatment, the sources usually are left in place for 5 to 7 days to deliver a
dose of 70 to 80 Gy to the target volume. An alternative is to use implants to supplement
the dose delivered with external beam irradiation. In this case a dose of 40 to 50 Gy is
delivered with external beam irradiation followed by a 2- to 3-day implant to deliver an
additional 30 to 40 Gy to bring the total dose to 70 to 80 Gy.

TABLE 101.1. PHYSICAL CHARACTERISTICS OF
COMMONLY USED BRACHYRADIOTHERAPY
SOURCES



RADIOBIOLOGY
Cell Death
Treatment must eradicate every viable cancer cell if the tumor is to be controlled with
radiation therapy. Cells are considered viable from a radiobiologic standpoint if they are
capable of unlimited division. They are considered dead if they cannot proliferate
indefinitely. It is not necessary that the cells be lysed or morphologically altered to be
considered killed. It is generally thought that reproductive cell death from irradiation is
caused by irreparable damage to DNA, although other targets may be important (1) (Fig.
101.3). The injury can occur directly, when a secondary electron produced by absorption
of an x-ray interacts directly with the critical target to produce damage, or indirectly,
when a secondary electron interacts with a molecule in the vicinity of the target to
produce a free radical, which damages the cell. In either case, the injury is inflicted close
to where the radiant energy is deposited. This is the basis of some of the radiobiologic
principles discussed herein.

FIGURE 101.3. Effects of radiation on DNA. A direct
effect occurs when a secondary electron interacts with
DNA. An indirect effect is caused by free radicals
produced by interaction between local molecules and a
secondary electron. (From Hall EJ. Radiobiology for the
radiologist, 4th ed. Philadelphia: JB Lippincott, 1994,
with permission.)



Random Nature of Cell Kill
Deposition of energy from a radiation beam is a random event, so is infliction of
radiochemical injury. This means that every cell in a tumor has the same chance of being
hit by a given dose of radiation. Because of this and other factors being equal, a given
dose of radiation kills the same proportion of cells in a tumor, not the same number of
cells. It takes the same amount of radiation to reduce the cell population from 100 cells to
10 cells as it does to reduce it from 10 billion cells to 1 billion cells.
This principle has several important implications for radiation therapy. First, it shows that
the amount of radiation needed to eradicate a tumor depends on the total number of
viable cells. A greater dose is needed to control a 3-cm tumor (which contains
approximately 10
10
cells) than a 1-cm tumor (which contains approximately 10
9
cells). It
also shows the fallacy of using clinical response rates to monitor the effectiveness of
treatment. A tumor is no longer palpable when the tumor has been reduced from 10
10
to
10
5
cells, yet only half of the dose needed to eradicate this tumor has been delivered. This
random nature of cell kill applies to both tumor cells and normal tissue. A therapeutic
advantage hypothetically is gained by means of the following mechanisms classically
known as the four Rs: repair (sublethal injury), reoxygenation (tumor cell hypoxia),
redistribution (cell cycle effects), and repopulation.
Sublethal Injury
When a secondary electron passes through matter, clusters of dense ionization are
distributed along an otherwise sparsely ionizing track. A cluster of dense ionization that
hits a sensitive target in the cell can inflict irreparable damage. If the target is hit with
sparse ionization, however, injury can be inflicted that is not sufficient to kill the cell. In
this situation, additional hits are needed to cause cell death. This sublethal injury can be
repaired by the cell if no further hits are incurred. Because of this, a greater dose is
needed to produce a biologic effect when it is given in several fractions than it is when it
is given in only a single fraction. In most tissues, sublethal injury is repaired within 3
hours, although it can take as long as 24 hours in some tissues (1).
The ability of a cell to repair sublethal injury between dose fractions is important to the
radiation oncologist for several reasons. One is that the biologic effect of irradiation
depends on the fractionation schedule. The greater the number of fractions, the greater is
the opportunity for repair between dose fractions and the greater is the total dose needed
to produce the same level of biologic effect. For example, a dose of 36 Gy in 12 fractions
(3-Gy fractions) over 2.5 weeks produces much more damage than 36 Gy in 18 fractions
(2-Gy fractions) over 3.5 weeks (Fig. 101.4).

FIGURE 101.4. Effect of fractionation. Hypothetical
model shows that 3,600 cGy in 12 fractions is equivalent
to 4,800 cGy in 24 fractions.



The concept of sublethal injury is important because certain tumors have more capacity
to repair sublethal injury than do others. For example, some malignant melanomas have a
remarkable capability for repairing sublethal injury, which may be responsible for the
belief that melanoma is a radioresistant neoplasm. Recognition of this biologic
characteristic has led some radiation oncologists to treat manage melanoma with
hypofractionated treatment schedules (a few large fractions), which minimizes the
opportunity for repair between fractions. Radiation therapy is fractionated because it
allows repair of injured normal tissue, which ultimately reduces late complications
related to radiation therapy. This provides a therapeutic advantage over tumor cells.
Tumor Cell Hypoxia
The presence of oxygen at the time of irradiation increases the effect of ionizing radiation
on biologic tissue. The mechanism by which oxygen radiosensitizes cells is not
completely understood. It is thought that when oxygen is present during formation of free
radicals from radiation, it fixes (makes permanent and irreparable) the damaged DNA
produced by the scavenging free radicals (1). In most biologic systems, the dose of
radiation necessary to kill hypoxic cells is 2.5 to 3 times greater than that needed to kill
well-oxygenated cells (Fig. 101.5).

FIGURE 101.5. Relation between oxygen concentration
and radiation sensitivity. Hypoxia is considered a major
cause of treatment failure.



Whereas normal tissues are almost always well oxygenated, cancerous tissue usually
contains hypoxic regions (4). Tumor cell hypoxia can be acute because capillaries can
collapse periodically or be compressed, or it can be chronic because tumors tend to
outgrow their blood supply (5) (Fig. 101.6). Hypoxic tumor cells usually reoxygenate
during a course of fractionated irradiation. This occurs because the requirements for
oxygen are diminished as tumor cells are depleted. The compressed blood vessels open,
or flow rate increases. Cells with chronic hypoxia are brought closer to capillaries as
well-oxygenated cells near the capillaries are eradicated. Reoxygenation is another
important reason for delivering radiation therapy in a fractionated course over time.

FIGURE 101.6. Hypoxic cells in lung cancer. The area
of necrosis is 160 mm from the nearest capillary. This
causes the hypoxic cells at the edge of necrosis to be
relatively radioresistant.



Cell Cycle Effects
Another factor that influences the radiosensitivity of a cell is its position in the cell cycle
(1,6). Cells undergoing DNA synthesis, the S phase, are much more radioresistant than
are cells in other phases of the cell cycle (Fig. 101.7). This is one reason a single large
dose of radiation is less effective in controlling a tumor than is a fractionated dose. When
treatment is fractionated, the cells surviving each fraction redistribute themselves into
more sensitive phases of the cell cycle, making them more susceptible to eradication by
subsequent fractions. The greater the number of fractions, the greater is the probability
that cells in a sensitive phase will be hit sometime during the course of irradiation. This
sensitizing effect of redistribution tends to offset the protective effect of fractionation
resulting from repair of sublethal damage. Redistribution is greatest for cells that are
rapidly cycling because rapidly cycling cells redistribute better between dose fractions
than do slowly cycling cells. The cells responsible for acute reactions, such as cells of the
skin and mucosa, cycle rapidly, and the cells responsible for late effects, such as
connective tissue, brain, and blood vessels, are cycle slowly. The net effect is that tissues
responsible for late complications are spared more by fractionation than are tissues
responsible for acute reactions.

FIGURE 101.7. Relation between radiosensitivity and
the cell cycle. Cells in the late S phase (LS) are
synthesizing DNA and are most resistant. M, mitotic
phase; G1, presynthetic phase; G2, postsynthetic phase.
(Modified from Sinclair WK. Time-dose relationships in
radiation biology as applied to radiation therapy. Report
50203 [C-57]. Berkeley, CA: Brookhaven National
Laboratory, 1969:97.)



Repopulation
Tumors are proliferating tissue. Because of this, it is not advisable to unnecessarily
protract a course of radiation therapy. If the tumor cell population is reduced, as with
surgery or irradiation, the malignant cells respond with accelerated repopulation (Fig.
101.8). Repopulation is a greater problem with rapidly proliferating tumors than it is with
slowly growing neoplasms. Accelerated treatment schedules with twice-daily
fractionation and combined accelerated-hyperfractionated schedules such as concomitant
boost techniques have been developed to diminish the opportunity for repopulation of
rapidly proliferating tu-mors. Repopulation after incomplete resection is one of the main
reasons for not delaying a course of postoperative radiation therapy. It is also a reason for
not dividing the treatment into several courses (split-course radiation therapy).

FIGURE 101.8. Tumor growth curves for a rapidly
proliferating tumor and a slowly proliferating tumor. The
initial growth of a tumor is exponential. However, growth
begins to plateau as the tumor enlarges, presumably
because of inadequate blood supply and a lack of
nutrients. When the tumor cell population is reduced, as
by surgery or irradiation, the malignant cells respond with
accelerated repopulation. The difference between the
growth rate of unperturbed tumor (AB) and the more rapid growth rate after surgery or
irradiation (A8B8) is evident. Accelerated regrowth is a greater problem with rapidly
proliferating tumors than with slowly proliferating tumors.



Dose-Response Relations
The probability of controlling cancer with irradiation depends on the size of the neoplasm
and the dose of radiation given (7) (Table 101.2). A dose of 50 Gy in 5 weeks controls
subclinical disease among 90% to 95% of patients and controls 1- to 3-cm masses among
50% of patients. A dose of 60 Gy in 6 weeks controls 1- to 2-cm masses among 80% to
90% of patients. A dose of 65 Gy in 6.5 weeks controls 2- to 4-cm tumors among 70% of
patients, and 70 Gy in 7 weeks controls 2- to 3-cm tumors among 90% of patients.

TABLE 101.2. LOCAL CONTROL AS A
FUNCTION OF RADIATION DOSE AND SIZE OF
THE TUMOR



The dose-response relation for small, well-vascularized tumors is steep. A moderate
increase in dose can increase the probability of local control from 25% to 75% (Fig.
101.9). This is because small, well-vascularized cancers are a relatively homogeneous
group of tumors. They are well oxygenated and have approximately the same number of
cells. The dose-response relation for bulky tumors is not as steep as it is for small tumors
because large tumors are a much more heterogeneous group of cancers. They have
considerable variability in number of cells and state of oxygenation (Fig. 101.9). The
dose-response relation for subclinical disease also is relatively shallow because the tumor
burden can range from only a few clonogenic cells to as many as 10
7
cells.

FIGURE 101.9. Dose-response curves as a function of
tumor burden. The dose-response relation for small
cancers is steep because these tumors are relatively
homogeneous in cell number and oxygenation. The dose-
response relation for large cancers is shallow because the
population of tumors is relatively heterogeneous. The
dose-response relation for subclinical disease is fairly
shallow because the tumor burden can range from a few
clonogenic cells to as many as 10
7
. The dose-response relation for tumor control is
represented by the left-sided solid lines. The dose-response relation for complications is
represented by the right-sided solid lines. The dashed lines represent subsets within a
heterogeneous population of tumors or tumor cell aggregates.



The dose-response relation for injury to normal tissue must be considered because the
risk of damage to normal tissue is what limits the dose administered to the cancer. With
small tumors, such as early vocal cord cancer, the dose-response curves for tumor control
and for normal tissue injury are well separated. In this situation, a high rate of local
control can be achieved with little risk of complications. With large tumors, the dose-
response curves for local control and for normal tissue injury are much closer together, so
even a moderate rate of local control carries a greater risk of complications (Fig. 101.9).
Regression Rates
Cell loss after irradiation is predominantly due to lysis at the time of mitosis, and most
cells divide four or five times before lysis occurs. Tumor regression rate is related to the
cycling time of the tumor cells. Rapidly proliferating tumors tend to regress quickly after
irradiation, whereas slowly proliferating cancers shrink more gradually. Because lethally
injured cells and surviving cells are morphologically indistinguishable, biopsy is of little
value in the early postirradiation period. For head and neck cancer, a positive biopsy
result usually is not a reliable indicator of persistent disease until about 3 months after
treatment (8).
TREATMENT
Selection of Treatment Modality
Selection of a treatment modality for a head and neck cancer is based on the size and
location of the primary tumor, the status of the regional lymph nodes, and the general
condition of the patient. Early-stage head and neck cancer usually is effectively managed
with either surgery or radiation therapy alone. The choice between surgery and radiation
therapy in these cases usually is determined by the functional deficit that would result
from each treatment. Larger cancers usually are managed with a combination of surgery
and radiation therapy. However, radiation therapy alone can be attempted and surgery
reserved for salvage if the tumor recurs. In general, surgery is more effective in salvaging
radiation therapy failures than is radiation therapy in salvaging surgical failures.
Radiation therapy failures usually occur in areas that were grossly involved with cancer
initially, often in the center of bulky masses. Surgical failures often occur at the periphery
of the operative field and in tissues that can be more hypoxic postoperatively because the
blood supply has been interrupted. Patients with massive tumors or with distant
metastatic lesions usually are treated palliatively. Palliation usually but not always is best
achieved with radiation therapy. The radiation doses needed for palliation of head and
neck cancer are similar to those needed for definitive treatment. Rapid courses of
radiation therapy usually are not feasible for the palliation of head and neck cancer
because the dose that can be delivered in a short time is insufficient for local tumor
control, and high weekly dose rates produce unacceptable acute reactions. Sometimes
palliative surgery, single-agent chemotherapy, or no treatment at all is the appropriate
choice for patients with massive head and neck disease.
Radiation Therapy Alone
Definitive treatment with radiation therapy can be delivered with external beam
irradiation, an interstitial implant, or a combination of the two. The choice usually is
based on the site and extent of the disease. Treatment with an implant alone is selected
only if the tumor is accessible and well circumscribed with little risk of regional lymph
node metastasis. If the disease is more extensive than this, external beam irradiation or a
combination of external beam and interstitial irradiation is selected. Neck nodes are
irradiated if there are clinically positive nodes or if there is considerable risk of
subclinical lymph node metastasis.
The tumor dose usually is based on the extent of the cancer and the tolerance of normal
tissue in the treated area. If the cancer is relatively small, doses of 60 to 65 Gy in 6 to 6.5
weeks may be adequate. Larger doses, such as 65 to 70 Gy in 6.5 to 7.5 weeks, are
needed for larger tumors. Even larger doses, such as 75 Gy in 7.5 to 8 weeks, may be
needed by patients with massive disease (Table 101.2).
Treatment usually is delivered with a shrinking-field technique (Fig. 101.10). An initial
tumor dose of 45 to 50 Gy usually is delivered in 4.5 to 5 weeks through large portals that
cover the clinically involved region and areas of possible regional lymph node metastasis.
The fields are reduced to encompass only the gross tumor with a small margin. An
additional 15 to 25 Gy is delivered with these boost fields to bring the total tumor dose to
60 to 72 Gy in 6 to 7.5 weeks. With massive tumors, there often is a second field
reduction at 60 to 65 Gy. In these cases, the residual disease is given an additional 5 to 10
Gy through small fields, bringing the total dose to 70 to 75 Gy in 7 to 8 weeks (Fig.
101.10). The spinal cord is limited to a dose of no more than 45 Gy to avoid the risk of
radiation myelitis.

FIGURE 101.10. Shrinking-field technique. The total
dose is determined according to the size of the tumor. A:
Initial portals encompass the gross tumor with wide
margins, including areas of possible nodal metastasis. B:
The first field reduction boosts the field to encompass the
gross tumor with some margin. The total dose is 6,500 to
7,000 cGy. C: The second field reduction is boosted
again for highly infiltrative primary tumors or large
nodes. The total dose is 7,000 to 7,500 cGy.



Combined Surgery and Radiation Therapy
The rationale for combining surgery and radiation therapy is based on fundamental
surgical and radiobiologic principles (Fig. 101.11). Surgical failures usually are caused
by residual microscopic disease, and radiation therapy failures usually are caused by an
inability to eradicate gross disease. When combined, these two modalities are
complementary. Surgery is used to remove gross masses too large to be eradicated with
moderate doses of irradiation, and radiation therapy is used to eradicate microscopic
extensions of tumor that cannot be excised. A postoperative dose of 58 to 66 Gy in 5 to
6.5 weeks is effective if the tumor has been reduced to a microscopic level. However,
larger doses are needed if there is gross residual disease or even histopathologically
positive margins (6,9) (Fig. 101.12).

FIGURE 101.11. Rationale for combined surgery and
radiation therapy. Surgical failures usually are caused by
residual microscopic disease, and radiation failures
usually are caused by inability to eradicate bulky masses.



FIGURE 101.12. Recurrence rates at the primary site
with and without postoperative radiation therapy.
Unsatisfactory margins include positive margins, close
margins (less than 0.5 cm), and margins containing in situ
carcinoma. RT, radiation therapy. (From Vikram B,
Strong EW, Shah JP, et al. Failure of the primary site
following multimodality treatment in advanced head and
neck cancer. Head Neck Surg 1984;6:720, with
permission.)



Preoperative Radiation Therapy
Once the decision has been made to deliver combined radiation therapy and surgery, the
physicians must decide which treatment modality to use first. The arguments in favor of
preoperative radiation therapy are as follows:
1. Unresectable lesions can be made resectable.
2. The extent of surgical resection can be diminished.
3. Before surgical intervention, the treatment portals usually are smaller than those
needed postoperatively.
4. Microscopic disease is more radiosensitive preoperatively because it has a better
blood supply.
5. The viability of tumor cells disseminated through surgical manipulation is
diminished, so the risk of distant metastasis decreases.
However, wound healing is more difficult after irradiation, and the dose delivered safely
before surgery is less than that given postoperatively. A typical preoperative dose is 45
Gy in 4.5 weeks. This dose is sufficient to eradicate subclinical disease among 85% to
90% of patients. However, it is less than the dose needed to control gross disease, and if
there are positive margins or gross residual disease after surgery, it is difficult to add a
meaningful dose postoperatively.
Postoperative Radiation Therapy
The arguments in favor of postoperative radiation therapy are as follows:
1. The anatomic extent of the tumor can be determined surgically, making it easier
to define the treatment portals.
2. A greater dose of irradiation can be given postoperatively than can be given
preoperatively.
3. The total dose to be given can be based on the residual tumor burden after
surgery.
4. Surgical resection is easier and healing is better in tissue that is not irradiated.
A theoretic disadvantage of postoperative radiation therapy is that distant metastasis can
be caused by cells spread in the surgical procedure. These cells might have been
eradicated with preoperative irradiation. Another problem is that postoperative radiation
therapy may have to be postponed if surgical healing is delayedcancer cells can
repopulate in the interval.
When radiation therapy is given postoperatively, a dose of 60 to 65 Gy usually is
delivered in 6 to 7 weeks. Higher doses may be needed if there is gross residual cancer.
Positive margins are considered evidence of gross disease because a fairly large number
of cells (10
6
to 10
7
) must be present to be detected even at microscopic examination by a
pathologist. Looser et al. (10) found that the presence of disease within 0.5 cm of the
surgical margins has the same prognostic implication as positive margins (Table 101.3).
Postoperative radiation therapy markedly reduces the risk of recurrence in the surgical
field. The results are poorer, however, if postoperative radiation therapy is delayed more
than 6 weeks (9).

TABLE 101.3. RECURRENCE RATE AS A
FUNCTION OF THE STATUS OF THE SURGICAL
MARGINS IN PATIENTS TREATED WITH
SURGERY ONLY



COMPLICATIONS
Acute Tissue Reactions
The time course for development of acute radiation reactions depends on the cycling time
of the cells affected (6,8). Initial mucosal reactions usually appear in the second week of
irradiation (Fig. 101.13). Maximal skin reactions appear in the fifth week. It is not
unusual to see reactive changes in the tumor (tumoritis) after only 1 week of treatment
if the tumor is rapidly proliferating. This can be a useful means of delineating the true
margins of poorly circumscribed tumors, such as cancer of the faucial arch. Acute effects
generally subside several weeks after completion of treatment and usually are not a
serious problem.

FIGURE 101.13. Acute mucosal reactions typically
appear at the end of the second week of radiation therapy.
(Modified from Fletcher GH, MacComb WS. A system
of radiation therapy. In: Fletcher GH, MacComb WS,
Shalek RJ, eds. Radiation therapy in the management of
cancers of the oral cavity and oropharynx. Springfield,
IL: Charles C Thomas, 1962:49, with permission.)



Late Tissue Reactions
Late effects are a concern because the injury often is permanent. The late effects of
radiation therapy for head and neck cancer include xerostomia, damage to the teeth,
fibrosis, soft-tissue necrosis, bone necrosis, cartilage necrosis, and damage to the eye, ear,
and central nervous system (Table 101.4). Xerostomia occurs when the salivary glands
are irradiated with doses larger than 35 Gy in 3.5 weeks. Even lower doses can greatly
decrease salivary gland function. Every attempt is made to limit the volume of salivary
gland tissue irradiated. Damage to the dentition usually is caused by xerostomia rather
than a direct effect on teeth or surrounding bone. Unlike other late effects of radiation
that occur primarily within the radiation portal, teeth both inside and outside the radiation
field can be affected.

TABLE 101.4. COMPLICATIONS RADIATION
THERAPY FOR HEAD AND NECK CANCER



Soft-tissue necrosis or osteoradionecrosis sometimes occurs among patients with head
and neck cancer. Soft-tissue necrosis manifests as mucosal ulceration and is thought to be
caused by damage to vascular connective tissue. Almost all cases of osteoradionecrosis of
the head and neck are caused by overlying soft-tissue necrosis. Cartilage necrosis can be
caused by necrosis of overlying soft tissue.
Severe skin damage is relatively uncommon because modern radiation therapy equipment
spares the skin. However, minor skin sequelae are frequent; they include epilation and
dryness due to loss of sweat and sebaceous gland function, thinning of the epidermis, and
telangiectasia. Fibrosis of the subcutaneous tissues and muscle is a serious problem and is
the principal dose-limiting factor of radiation therapy today. In severe cases, the tissue
can develop a woody texture and become fixed into a single hard mass. Administration of
large daily fractions and therapy for massive neck disease increase the risk of
subcutaneous fibrosis.
The ocular complications of radiation therapy include cataracts, radiation retinopathy,
optic nerve injury, and lacrimal gland damage. Cataracts can occur with doses as low as 6
Gy, and radiation retinopathy or optic nerve injury can occur with doses in the range of
50 to 55 Gy. The lacrimal glands are similar histopathologically to salivary glands and
are highly sensitive to radiation. The nasolacrimal drainage system, however, usually is
radioresistant. Serous otitis media is a frequent complication of radiation therapy for
paranasal sinus and nasopharyngeal cancer. It usually is transient and is caused by edema
of the mucous membranes lining the eustachian tube. Sensorineural hearing loss is a
rarely reported complication of ear irradiation, but it is probably more common than
generally believed.
Radiation damage to the brain or spinal cord is rare, but it is a concern to radiation
oncologists because the results are devastating. Transient radiation myelopathy can occur
with doses as low as 30 Gy in 25 fractions. This is a transitory syndrome characterized by
electric shock sensations triggered by flexing the cervical spine (Lhermitte sign).
Transverse myelitis is a rare complication that can occur after doses of 50 to 60 Gy in 5
to 6 weeks. Radiation effects on the brain can be transient or permanent. Somnolence
syndrome is a transient condition that is self-limited and characterized by lethargy,
nausea, headache, cranial nerve palsy, or ataxia. It usually appears 2 to 3 months after
treatment and lasts 2 to 4 weeks. Brain necrosis is a permanent injury that can develop
after doses in the range of 65 to 70 Gy.

HIGHLIGHTS
Every viable clonogenic cancer cell must be eradicated if a
tumor is to be controlled with radiation therapy. Cells are
considered viable if they are capable of unlimited division.
The biologic effects of irradiation depend on the fractionation
schedules used. The larger the number of fractions, the greater
is the total dose needed to produce a given level of damage.
The presence of oxygen in the targeted tissues enhances the
biologic effects of radiation.
After a tumor cell population is reduced by surgery or
irradiation, the cells respond with accelerated repopulation.
This is one of the main reasons for not delaying postoperative
radiation therapy and not delivering radiation therapy in a split
course.
The two biologic factors that determine the probability of local
control with irradiation are the number of malignant cells and
the proportion of these cells that are hypoxic. Both of these
factors are principally related to the size of the tumor.
Small, well-vascularized, exophytic tumors usually respond
well to irradiation; large, infiltrative, or ulcerative cancers are
less responsive.
The probability of controlling head and neck cancer with
radiation therapy is related to the size of the neoplasm. A dose
of 50 Gy in 5 weeks controls subclinical disease among 90% to
95% of patients; 65 to 70 Gy in 6 to 7 weeks is needed to
control gross masses. Because lethally injured cancer cells and
surviving cancer cells are morphologically indistinguishable,
biopsy is of little value in the early postirradiation period, that
is, within 3 months.
Radiation therapy for head and neck tumors usually is delivered
with a shrinking-field technique. The initial portals are
relatively large, encompassing the gross tumor and areas of
possible clinical involvement. The boost fields usually
encompass only the gross tumor with a small margin.
CHAPTER REFERENCES
1. Hall EJ. Radiobiology for the radiologist, 4th ed. Philadelphia: J.B. Lippincott, 1994.
2. Khan FM. The physics of radiation therapy, 2nd ed. Baltimore: Williams & Wilkins, 1994.
3. Delclos L, Sampier V. Special gamma-ray techniques. In: Fletcher GH, ed. Textbook of
radiotherapy. Philadelphia: Lea & Febiger, 1980:71.
4. Thomlinson RH, Gray LH. The histological structure of some human lung cancers and the
possible implications for radiotherapy. Br J Cancer 1955;9:539.
5. Brown JM. Evidence for acutely hypoxic cells in mouse tumours and a possible mechanism of
reoxygenation. Br J Radiol 1979;52:650.
6. Fletcher GH. The role of irradiation in the treatment of squamous cell carcinomas of the mouth
and throat. In: Nahum AM, Bush S, Davidson TM, et al., eds. Head and neck surgery. Boston:
Houghton Mifflin, 1979:441.
7. Fletcher GH. Basic principles of radiotherapy: basic clinical parameters. In: Fletcher GH, ed.
Textbook of radiotherapy. Philadelphia: Lea & Febiger, 1980:180.
8. Fletcher GH, MacComb WS, eds. Radiation therapy in the management of cancers of the oral
cavity and oropharynx. Springfield, IL: Charles C Thomas, 1962:49.
9. Vikram B, Strong EW, Shah JP, et al. Failure of the primary site following multimodality
treatment in advanced head and neck cancer. Head Neck Surg 1984;6:720.
10. Looser KG, Shah JP, Strong EW. The significance of positive margins in surgically resected
epidermoid carcinomas. Head Neck Surg 1978;1:107.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

102 TUMOR BIOLOGY AND IMMUNOLOGY OF HEAD AND NECK CANCER
Head & Neck SurgeryOtolaryngology
102




TUMOR BIOLOGY AND IMMUNOLOGY OF HEAD
AND NECK CANCER
WILLIAM J. RICHTSMEIER

W.J. Richtsmeier: Department of OtolaryngologyHead and Neck Surgery, Bassett Healthcare,
Cooperstown, New York.


Molecular Diagnosis
Advances in Basic Immunology
Tumor Cell Antigens
Effector Mechanisms Against Head and Neck Cancer
Immunoglobulin Structure and Function
Cellular Effectors
Cytokines
Interferons
Interleukins
Exogenous Immunosuppression
Immunotherapy
Chapter References
Tumor immunology is the study of the complex interaction between an individual and a
neoplasm, which unless adequately treated causes the death of the host. An interest in the
relation between the immune system and tumors goes back to the infancy of immunology
and is intimately connected to three areas of study. First, it is related to infection and the
science of humoral and cellular immunity. Second are the studies of transplantation and
the science of rejection and tolerance. Third are wound healing and the science of
cytokines and cell-growth promoters.
Head and neck cancer is an ironic circumstance in which immune-competent cells kill
tumor cells and many patients with head and neck tumors have marked anergy, that is,
loss of immunologic energy. Much early work centered on the types of immune effector
cells in tumors. This approach, however, provided only limited understanding of how
cancers escape immune killing.
Tumors are generated through a number of pathways to produce a common phenotype
that dissected genetically has proved to be a heterogeneous collection of genotypes (1).
One of the most interesting tumor-associated genetic defects is that of p53, a molecule
important in the internal mechanisms built into a cell to ensure its destruction if genetic
misinformation occurs in copying the cell during cell division. p53 proved to be an
important final pathway in the generation of colon cancer among patients with familial
polyposis; however, it has not been routinely found among patients with head and neck
cancer. Only one half to two thirds of these patients have p53 gene defects. Cancer cells
can circumvent the normal cellular pathways in numerous ways to prevent such genetic
mistakes from occurring. Multiple genetic pathways means that numerous protein
messengers affect cell growth and therefore that expression of tumor antigens is
inconsistent.
One method by which cells gain genetic information that renders growth control
mechanisms inadequate is viral transformation. A number of transforming viruses,
including human papilloma virus (HPV) and the herpes simplex virus group have been
associated with, and at one time or another implicated in, the generation of head and neck
cancer among some individuals. Genetic transformation increases the potential for cells
to display new antigens either internally or externally and allows immune detection. This
complex genetic assortment of cancer characteristics is being investigated with
microarrays that can screen thousands of genes on a slide or tiny chip.
MOLECULAR DIAGNOSIS
Tumors originate clonally from cells that have acquired genetic alterations. Oncogenes
increase cell growth and mutations and cause the loss of tumor suppressor genes that
control cell growth and are both needed to produce the cancer phenotype (1). The original
model of genetic progression proposed by Vogelstein et al. (2), which required sequential
acquisition of several mutations, has been studied among patients with head and neck
cancer in the laboratory at Johns Hopkins University (3). The loss of chromosomal region
9p21 is the most common genetic error and appears early in the progression of cancer.
Inactivation of the p16 gene, an inhibitor of cyclin and cyclin-dependent kinases, is an
important event in regulation of the cell cycle (4). About half of head and neck tumors
contain mutations of the p53 gene, located at 17p13 (5). Loss of cell program death
appears to occur in other tumors and arises through a different mechanism resulting from
HPV virus infection. Sidransky (1) reported that more than one half of tumors originating
in the oropharynx contain HPV, and this patient population is less likely to be heavy
smokers and drinkers (1). The HPV viral protein E6 appears to degrade p53 gene product
as a substitute explanation for the defective mechanism of controlled cell death
(apoptosis). Patients with HPV infection have a better overall survival rate and better
disease-specific survival rate than do patients with p53 mutations. It appears that HPV
infection is a distinct pathologic entity that can be separated out prospectively. This
finding also raises the possibility of vaccines as an approach to protecting these patients.
Protooncogenes, which increase cell growth, are present in squamous cell carcinoma of
the head and neck. About one third of tumors studied in some series have amplification of
cyclin D1. Although amplification of the epidermal growth factor receptor (EGFR) gene
is rare, overexpression is frequently observed. Many cells in the perimeter of head and
neck cancers have genetically transformed cells that have not changed phenotype (6).
This may explain the phenomena of field cancerization and recurrence in anatomically
clear margins.
Early detection of cancer has been the most important advance in almost every area of
oncology. Sidransky et al. (1) used a panel of 21 microsatellite markers to detect clonal
genetic changes in cytologic specimens from patients with head and neck cancer. Eighty
percent of saliva samples from the patients with head and neck cancer were positive,
whereas specimens from patients who acted as controls, including smokers, were
negative. It is desirable to find a serum marker for head and neck cancer similar to that
available for prostate cancer, prostate-specific antigen. Along those lines, in experiments
to identify free DNA circulating in the serum of patients with head and neck cancer,
investigators have identified microsatellite alterations (7). Nasopharyngeal carcinoma
stands out in this regard in that Epstein-Barr virus (EBV) is intimately identified with this
disease; therefore the serum antigens have long been associated with this type of tumor.
The presence of EBV virus DNA is a quantitative predictor of disease among patients
undergoing primary radiation therapy (8).
Assessment of potential positive margins by means of molecular biologic techniques has
identified p53 mutations in apparently normal cellular phenotype. Approximately one
half of the patients who underwent resection were found to have p53 mutations. The
contribution that this knowledge offers to radiation resistance or recurrence is of interest.
Other genetic errors such as eIF4E have been used to survey tumor resection margins and
predict recurrence considerably better than routine pathologic examination (9).
Therapies aimed at EGFR and the cyclin-dependent kinase inhibitors (P16) have been
developed. These treatments have been used alone and with radiation therapy and can be
models with antibodies to EGFR and gene therapy to change EGFR expression in tumors.
Genetic therapy to replace a defective p53 gene also has been of interest. This approach
has frequently involved adenoviruses, which have high epithelial cell infectivity. It also
entails efficient transformation of receptor cells by the new gene product and selective
use of a mutant adenovirus that cannot replicate. The wild-type p53 gene, when
transfected and expressed, allows cells to undergo apoptosis and may provide additional
immune exposure to antigens in the tumor response.
ADVANCES IN BASIC IMMUNOLOGY
Before proceeding further with discussion of the known interactions between tumors and
their hosts, it is worth reflecting on basic immune functions that are early events in the
immune surveillance system. For many years it was thought that immune competence
occurred around the time of birth among mammals and that embryos or the very young
did not have competent immune systems. Embryos and newborns were thought fairly
immune tolerant. Many of these concepts came from experiments in the 1950s, an
example of which is attributed to Billingham et al. (10). The original experiments
involved removing hemopoietic stem cells from newborn, inbred (genetically
homogeneous), mice and injecting the cells into mice of a different skin color. Scientists
already knew that inbred mice tolerate skin grafts from their litter mates but not from
mice with a different genetic composition (mice with a different skin color). In such an
experiment, a skin graft from one species to another can be followed quite easily because
of the obvious color difference. Skin grafts from the test animals normally placed on a
control animal were rejected within a relatively short period of time. Test animals that
had received injections with stem cells in newborn life became tolerant of skin grafts
from the stem cell donor species even after they had become otherwise immunologically
competent. They rejected grafts from mice different from either of the groups tested.
The concepts of newborn immune competence were revisited by Ridge et al. (11). These
investigators used an immunologic difference present in otherwise genetically identical
mice. In the test system, the only difference from animal to animal occurred among males
that carried an additional antigen on the cell surface. The females lacked this antigen.
Such an experiment, with a single different antigen between all the test animals, was a
unique circumstance to test various hypotheses. The investigators observed that when
spleen cells or B cells from male mice were injected into female mice in the newborn
period, the mice became tolerant and lacked specific cellular killing mechanisms to
identify the male cells in a controlled test later. If, on the other hand, dendritic cells were
harvested from the male mice, concentrated, and injected into the females, the female
mice developed specific cellular toxicity for cells displaying the male antigen. This series
of experiments showed that the ability to obtain either tolerance or specific immunologic
activity can be controlled by the presence or absence of dendritic cells or tolerizing B
cells. The opportunity for immunologic activity basically involves an activated dendritic
cell coming in contact with a virgin T cell. Any other combination causes no response or
tolerization. Because there are many more B cells (and activated T cells) in the donor
inoculum than there are dendritic cells, the relative abundance of the tolerizing B cells
coming in contact with virgin T cells renders the recipient animal tolerant of any antigens
that are on the injected B cells. Activated dendritic cells, which display their own surface
antigens the same as they would antigens ingested from another source, can make a killer
T cell when they come into contact with the virgin T cell in the proper circumstance.
These activated T cells propagate and allow specific immunologic activity against one
antigen. In the newborn period, when dendritic numbers are small, it is much more likely
that the donor inoculum causes tolerance than specific immunologic memory. Being able
to alter the numbers and activity of dendritic cells displaying any given antigen is an
important part of the immune response. The immune system typically is not inclined to
respond to antigens of the host, and there are reasons control of this type of reaction must
be maintained. Otherwise, the individual would quickly die of autoimmune disorders.
Therefore, a dendritic cell not activated but expressing some of its own antigens on its
surface must have a way of not activating a virgin T cell.
A number of mechanisms have been identified that affect the relation between dendritic
cells and lymphocytes and that are important in tumor immunology. The T cell must
come into intimate contact with the dendritic cell as part of the antigen recognition
process. As shown in Fig. 102.1A, dendritic cellT cell interaction involves, first,
presentation of the antigen in the major histocompatibility complex (MHC) and, second,
activation of CD28 (T cell) and b7.1 (or b7.2) on the dendritic cell. If both these
conditions are not met, the molecule in the antigen MHC is considered nonantigenic or
tolerant by the dendritic T-cell system. Tumor cells produce substances such as CTLA-4,
which binds more intensely to CD28 than the b7.1 locus and therefore confers T cells
immunologically tolerant. Although this specific mechanism has not been found present
in head and neck cancer, such tolerance has already had power in human transplantation.
Pre-exposing a patient to donor cells in the presence of CTLA-4 has produced what
appears to be lifelong graft tolerance that requires no ongoing immunosuppression.

FIGURE 102.1. A: Near the bottom, tumor cells
influence the interaction between dendritic cells and
lymphocytes and recruitment of predendritic cells, CD34-
positive cells, into the tumor environment. Tumor
production includes granulocyte-macrocyte colony-
stimulating factor and IL-1 and other inflammatory
mediators. The predendritic, CD34 positive cells,
however, do not differentiate into active dendritic cells
but can be recruited to other activities, which occurs in the presence of squamous cells
condition media. One such substance may be able to induce differentiation of CD34-
positive cells to CD31 endothelial cells promoting new blood vessel formation for tumor
nutrient supply and growth. B: The cancer cell in the lower portion of the illustration is
shedding antigen, which is processed by the dendritic cell and competes for presentation
to T cells and normally produced proteins from its own endoplasmic reticulum. All
antigens must be presented in the major histocompatibility antigen complex and the
binding of b7.1 or b7.2 on the surface of the dendritic cell and CD28 on the T cell. The
dendritic cell must be in an active form, which can be brought about by heat shock
protein or other mediators.



Dendritic cells have no specificity in terms of the antigens they present and therefore
antigens that happen to occur on the surfaces of these cells because of normal biologic
characteristics can be presented to T cells. As shown in the lower left portion of Fig.
102.1B, internally produced antigens are expressed in the same way as tumor antigens,
which undergo pinocytosis and are delivered to the surface for antigen presentation. That
is, proteins produced by the dendritic cell endoplasmic reticulum have the same chance of
being expressed to a T cell as one that undergoes pinocytosis. In the case of the male
mice in the experiments by Ridge et al. (11), the normal male antigen on the transplanted
male dendritic cells is constitutive and interacts with the female virgin T cells to start
anti-male cytotoxicity. This lack of selectivity due to dendritic cells requires a number of
mechanisms to assure that an individual does not react inappropriately to a self antigen.
TUMOR CELL ANTIGENS
The foundation of the antitumor response rests on the ability of the immune system to
differentiate between normal and malignant cells. It has been postulated that tumor cells
express distinct antigens that allow the immunologic surveillance mechanisms to discern
normal from malignant tissue. Truly unique tumor antigens, those antigens detected only
on tumor cells and not the remaining cells of the host, have been difficult to identify in
head and neck cancer. Tumor-associated antigens have been found on both normal and
malignant cells, and differentiation between the two types of cells is possible because of
qualitative and quantitative differences in expression (12). Examples of tumor-associated
antigens are the blood group antigens,
2
-microglobulin, and some of the antigens
normally found in differentiated squamous epithelium, such as keratin (13,14).
The advent of monoclonal antibody technology has allowed the development of
antibodies that bind to a number of types of squamous cell carcinoma, although none has
been found completely specific for the malignant cells. Two such monoclonal antibodies
are E48, which are used to detect an antigen expressed exclusively by squamous
epithelium in the region of the desmosome, and A9, a member of the integrin family that
serves as a cell attachment receptor for laminin and may be involved in the development
of metastasis. These antibodies may have utility for diagnosis and treatment (15,16).
Tumor cells also express other surface antigens that have a direct role in the generation of
immunologic signals. The quantity of these immunologically active antigens may be
affected by exposure to cytokines. One MHC class II (MHC-II) molecule, HLA-DR,
which is involved in the processing of antigenic signals, has been found on the surface of
squamous cell carcinoma of the head and neck by means of induction with interferon-
(IFN-) (17). Major histocompatibility complex class II is involved in processing of
foreign antigens and may have a similar role in head and neck cancer. Other antigens
identified on the surface of squamous cell carcinoma are the intercellular adhesion
molecule, which functions as a ligand for cytotoxic T lymphocytes, and other cell
adhesion molecules, such as CD44 epithelial cadherin, the integrins
6
and
1
, and sialyl
Lewis X (18,19).
Additional mechanisms that influence this early step in the immune system were
identified when it was observed that large numbers of dendritic cell precursors were
present in the peripheral blood of patients with a variety of cancers. These cells, which
are CD34+, apparently are recruited through the effects of granulocyte-macrophage
colony-stimulating factor, which is produced by head and neck tumors (20). In this
model, the proportion of CD34+ cells may be as high as 5% of the peripheral blood
mononuclear cell population. With such a large number of dendritic cell precursors, why
is there such a poor immune response? There seem to be multiple methods for interfering
with maturation of dendritic cells. The mechanisms include tumor production of
interleukin-10 (IL-10) and production of a material that interferes with many aspects of
immune response, p15e, a retroviral antigen similarity to interferon-alpha (IFN-). It also
appears that tumors may be able to influence differentiation of CD34 cells to CD31+
endothelial cells. Therefore, tumors recruit predendritic cells but pervert the response by
changing them into cells, which only contribute to neovascularization of the tumor and
inhibit immune potential. Another tumor-associated immunosuppressive product
produced by squamous cell carcinoma of the head and neck is prostaglandin E
2
, which
inhibits growth of T cells in a system in which specific tumor-associated lymphocytes are
harvested and grown in culture. Prostaglandin E
2
influences tumor neovascularization.
Experiments with implantation of corneal tumors in rabbits have shown cessation of solid
tumors elsewhere than in the head and neck. Neovascularization with cyclooxygenase
inhibitors raises the possibility of therapeutic intervention with this class of drugs (21). In
an evaluation of immune suppression, Young et al. (20) found a multiplicity of non
mutually exclusive mechanisms of immune suppression that reduced CD8+ cell influx
and altered function of intratumor CD4 cells. Other possible mechanisms of tumor
immunosuppression are listed in Table 102.1.

TABLE 102.1. POSSIBLE MECHANISMS OF
IMMUNOSUPPRESSION IN HEAD AND NECK
CANCER



EFFECTOR MECHANISMS AGAINST HEAD AND NECK CANCER
The effector components responsible for surveillance and destruction of malignant
disease include the cells of the circulatory and lymphoreticular systemslymphocytes,
monocytes, macrophages, dendritic cells, and endothelial cells, and the secretory products
derived from these cellular constituentsthe immunoglobulins and cytokines. Although
the cellular and humoral parts of the immune system often are considered separately, it is
important to recognize that an effective immunologic response depends on the complex
interactions and regulatory effects that each exerts on the other. This integrated immune
mechanism can behave differently depending on tumor and host factors; as such, precise
delineation of the antitumor response is difficult.
Another old perspective was that newborns were thought to be poor responders to
vaccine. Many studies have shown that young animals simply have to have the vaccine
dose decreased so that it does not overwhelm the newborn T lymphocytes before the
dendritic cells can activate them (22). This perspective also leads to the newer concept
that three steps rather than two are needed to activate the immune system. It was known
that a specific antigen triggered the immune response after being recognized by the T-
lymphocyte receptor plus a nonspecific signal provided by dendritic cells, which were
costimulated. It now appears that the second signal is delivered only after the dendritic
cell has been activated by other stressed, damaged, or otherwise injured cells through a
danger signal. In this way, graft rejection and cancer are closely linked. Damaged cells
that give the danger signal are critical in activating the response to cancer. One candidate
group of molecules for the danger signal is heat shock proteins (23).
IMMUNOGLOBULIN STRUCTURE AND FUNCTION
Central to an understanding of the immune response to cancer is recognition of the role of
the immunoglobulins in the effector mechanism. The immunoglobulins are serum
glycoproteins produced by B lymphocytes in response to foreign antigens. The hallmark
of the immunoglobulins is their specificity; they are able to bind directly to the substance
that elicited their production, thus functioning as antibodies. Each immunoglobulin
molecule is composed of two heavy (H) and two light (L) chains, each with variable (V)
and constant (C) regions. This composition provides a tremendous degree of structural
diversity. Classification of the H and L chains based on differences in the constant
regions allows differentiation into two types of L chains, and , and five types of H
chains, , , , , and . The H-chain classification determines the class of
immunoglobulin molecule, hence the five classesIgG, IgA, IgM, IgE, and IgD. The
antigen-binding site is formed by amino acid sequences located in the V regions of the H
and L chains. En-zymatic cleavage by papain results in digestion of the immunoglobulin
molecule into two Fab (antigen-binding) fragments and an Fc (crystallizable) fragment
that can combine with a cell surface receptor located on certain leukocytes Fig. 102.2.

FIGURE 102.2. Diagram shows immunoglobulin
molecule with associated antigen-binding and functional
domains. Enzymatic cleavage with papain splits the
molecule into Fab and Fc regions. IgG, IgE, and IgD exist
as monomers. Secretory IgA is present in a dimeric form
joined by one secretory molecule and one J chain.
Immunoglobulin M normally exists as a pentamer.



A great deal of the immunologic diversity attributable to immunoglobulins occurs
through genetic recombinations that change the antigenic determinants of the variable
regions (idiotypes). This provides functional antibody specificity, but further diversity
also occurs through variation in the class and subclass of the H and L chains (isotypes)
(24). In this way, the immunoglobulins have antigenic specificity as well as differences in
secondary biologic activities Table 102.2.

TABLE 102.2. BIOLOGIC PROPERTIES OF THE
HUMAN IMMUNOGLOBULINS



The immunoglobulins primarily involved in the immunologic response to cancer include
IgG and IgA. Immunoglobulin G is the predominant immunoglobulin molecule in the
serum and appears to have an important role in cytotoxic events directed against
malignant cells. Two mechanisms involving IgG are active in this regard. Complement
fixation to IgG molecules bound to tumor cells can cause cell death. Molecules in the
serum of patients with head and neck cancer can bind C1q, the first component of the
complement pathway. These mole-cules may be circulating immune complexes
composed of immunoglobulin bound to tumor antigens. This can have a deleterious effect
on the function of complement-mediated cytotoxicity, because elevated levels of C1q
binding carries a poor prognosis for patients with advanced-stage disease who are
undergoing induction chemotherapy (25).
An alternative and perhaps more efficient mechanism involves antibody-dependent
cellular cytotoxicity, in which the immunoglobulin molecule, usually IgG, binds to a
specific antigenic target on the tumor cell and attaches to an effector cytotoxic cell
through the Fc receptor. A number of immune cells can be effectors, each expressing the
Fc receptor on the cell surface. Cells that appear capable of participating in this cytotoxic
response include helper T and cytotoxic T lymphocytes, monocytes, macrophages,
eosinophils, neutrophils, and platelets. Antibody-dependent cellular cytotoxicity
functions in vitro in the immune response to squamous cell carcinoma of the head and
neck by means of peripheral blood lymphocytes directed against pemphigus antigen
present on the malignant cells (14). The previous finding of detectable levels of
circulating antitumor antibodies in patients with squamous cell carcinoma of the head and
neck supports the role of antibody-dependent cellular cytotoxicity tumor surveillance in
vivo (26).
The function of IgA in the immunologic response to cancer is less clear. Immunoglobulin
A exists in both a monomeric circulatory form and a dimeric secretory form attached to a
secretory component. Immunoglobulin A cannot bind complement in either form,
although the circulatory form can activate the alternative pathway if aggregation of the
immunoglobulins occurs; however, this pathway does not appear to be physiologically
active. Immunoglobulin A does not elicit a chemotactic or phagocytic response after
binding to antigen. As a result, IgA may confer a protective effect for the benefit of the
tumor by isolating malignant cells from cytotoxic mediators.
CELLULAR EFFECTORS
The immune response to cancer centers on the function of the lymphocyte. Lymphocytes,
which compose approximately 20% of the circulating leukocytes, are divisible into three
general classesT cells, B cells, and natural killer (NK) cells. The use of monoclonal
antibodies directed against cell surface antigens has marked heterogeneity among the
lymphocytes and allows further differentiation into distinct subsets with differing
functions (Table 102.3). Characteristic surface markers, designated clusters of
differentiation (CD), and the specific antigen receptors present on each cell are used to
classify lymphocytes. T cells recognize antigen by means of a specific T-cell antigen
receptor complex, designated CD3. Further distinction into two T-cell subsets is possible
on the basis of the relation of the T cells to MHC molecules. T cells expressing the CD4
molecule, mainly representing helper T cells, require MHC-II (HLA-DR) for antigen
presentation, although lymphocytes expressing the CD8 molecule, cytotoxic T cells,
respond to antigen associated with MHC-I (HLA-A, HLA-B, or HLA-C). CD4 T
lymphocytes mediate their response by means of stimulating other effector cells, whereas
activated CD8 cells cause direct cytolysis. B lymphocytes express surface
immunoglobulin that functions as the antigen receptor. Unlike T cells, B lymphocytes can
bind directly to antigens without the need for MHC molecules. B cells also have Fc
receptors on the cell surface, although the binding affinity for extrinsic immunoglobulin
molecules attached to this receptor is much lower than that for the expressed native
immunoglobulin.

TABLE 102.3. SELECT LEUKOCYTE SUBSETS
AND CD CLASSIFICATIONS



Activation of B cells can occur by means of T cellindependent or T celldependent
antigen stimulation. In the first case, clonal proliferation and immunoglobulin production
occur without helper T-cell interaction. T celldependent activation requires helper T-cell
recognition of the antigen and subsequent production of soluble mediators, including IL-2
and IL-4, which stimulate B cells to respond. The third subset of lymphocytes, the NK
cells, express neither the T-cell receptor complex nor the B-cell immunoglobulin receptor
and appear to represent a distinct lineage. Natural killer cells can be identified through
expression of certain differentiation antigens, namely the IgG Fc receptor (CD16) and
CD56. Among healthy persons, NK cells compose 10% to 15% of the circulating
lymphocyte pool and are present in the bone marrow and spleen. These cells appear to
have marked cytotoxic antitumor activity, which does not depend on prior antigen
exposure or MHC restriction. Enhanced cell killing also exists for NK cells activated by
the cytokine IL-2 (27). These activated cells, known as lymphokine-activated killer (LAK)
cells, can lyse fresh tumor cells. Other cytokines such as IFN- and IFN- also seem to
provide NK cells with increased cytotoxic activity (27). In addition to their role as direct
cytotoxic effectors, NK cells mediate antibody-dependent cellular cytotoxicity and
influence the function of other effector cells by secreting cytokines.
Other cells are recognized as having a role in the immune response to cancer. Most
notable are the monocytes and macrophages, constituents of the reticuloendothelial
system. Monocytes, present in the circulation, differentiate into mac-rophages, which
function as phagocytic and immunoregulatory cells. Monocytes and macrophages can be
differentiated from other lymphoid cells through identification of their cell surface
antigens, including MHC-I and MHC-II molecules, interferon receptor, complement
receptors, and Fc receptors CD32 and CD64.
Important in the antitumor response by macrophages is their function as antigen-
presenting cells for T lymphocytes. Macrophages can process and present antigen to both
CD4 and CD8 T cells, allowing activation of these lymphocytes against malignant cells.
Activated lymphocytes in turn produce cytokines that enhance the antigen-presenting
capabilities of the macrophages and stimulate them to develop direct tumoricidal activity.
Other antigen-presenting cells, apparently of leukocytic origin, have been isolated from
patients with head and neck cancer. These cells, called dendritic cells, may be important
in presentation of tumor-specific antigen.
CYTOKINES
The antitumor responses of the immune system depend on a group of immunomodulatory
peptides, the cytokines, produced mostly by the mononuclear cells. These cellular
products have true hormone-like activity, although in most cases their activity is directed
locally in the microenvironment in a paracrine manner. Cytokines produced by
lymphocytes are called lymphokines. Those produced by monocytes are called
monokines. These cytokines once were identified and classified according to their in vitro
functions with such names as T-cell growth factor and macrophage-activating factor.
In the immune response to cancer, the functions of the cytokines are protean. They
regulate and activate other cellular effectors, exert growth and differentiation effects on
the tumor cells and surrounding tissues, and participate directly as cytotoxic agents. The
target cell effects of the cytokines are mediated through specific receptor interactions,
presumably located at the cell surface. Technologic advances that allow cloning of the
genes for the cytokines enables large-scale production of homologous products that fuel
the investigative uses of these agents. Cytokines that have received the most intense
investigation in the antitumor response to head and neck cancer are as follows.
Interferons
As a group, the interferons have received a great deal of attention as immunomodulatory,
antiinflammatory, and cytotoxic agents. Interferon was originally recognized as a
secretory protein produced in response to viral infection that conferred antiviral
protection to cells. Since the initial discovery, three distinct subclasses of interferon have
been identified, and a variety of stimuli elicit their production. Two of the subclasses,
IFN- and IFN-, have been called type I interferons. These agents are produced in
response to viral infection or exposure to double-stranded RNA and remain stable during
exposure to acid. Interferon- is produced by most leukocytes; IFN- is produced by
connective tissue cells. In contrast, IFN-, type II interferon, is produced only by T
lymphocytes and large granular lymphocytes in response to antigenic stimuli and is labile
at acidic pH (13).
In addition to their antiviral effects, interferons mediate a broad range of biologic
responses, including antitumor cytotoxicity, inhibition of cell proliferation, gene
activation, modulation of cell surface antigens, immune cell activation, and stimulation of
other cytokines and immunomodulators. These effects occur as a result of direct binding
of the interferon to specific cell surface receptors on the target. Different receptors exist
for the type I and II interferons, both receptors exhibiting high-affinity binding. After
internalization of the interferon-receptor complex, synthesis of specific messenger RNAs
and proteins occurs that modulates the biologic effect. Some products induced by
interferon include the MHC antigens, a protein kinase, and 2'5'-oligoadenylate synthetase
(27). These enzymes have a role in the antiviral effects, although the MHC antigens are
intimately involved in the immune response mechanism. The exact events responsible for
the cytolytic and cytostatic effects of the interferons are not yet resolved. However, the
expression of a number of protooncogenes, including myc, ras, mos, and abl, is affected
by interferon (27).
Interferon- has a more potent immunomodulatory effect than the type I interferons.
Direct cytotoxic effects have been seen in vitro against squamous cell carcinoma of the
head and neck, with both cytolytic and cytostatic results (28). These responses depend on
the cumulative dose of IFN- and the duration of exposure. In vivo, IFN- can cause
cytolysis and increase tumor cell differentiation (29). Interferon- also may enhance the
cell-mediated response to head and neck cancer. Activation of macrophages and NK cells
by IFN-, with increased expression of the Fc receptor, enhances the tumoricidal
capabilities of these cells and promotes the antigen-presenting function of the
macrophages. Interferon- also induces expression of the MHC-II antigen and the
intercellular adhesion molecule on tumor cells and lymphocytes, which may contribute to
the chemotactic and antigen-presenting functions necessary for an effective immune
response (17,29). Interferon- also can enhance the antitumor effects of other cytokines,
such as tumor necrosis factor (TNF).
Interleukins
The interleukins encompass a group of proteins produced by leukocytes and other cells
that exert a wide array of overlapping immunologic and nonimmunologic actions. A
number of interleukins have been identified. Many are labeled with numerals, such as IL-
1, along with the closely related cytokines TNF- and TNF-. Although the complex
functions of these cytokines are being intensely investigated, certain effects are clearly
important in the immune response to cancer.
Interleukin-1, originally known as lymphocyte-activating factor, has diverse
immunologic, inflammatory, and reparative actions. This cytokine is produced by most
nucleated cell types, including macrophages, dendritic cells, keratinocytes, lymphocytes,
endothelial cells, and fibroblasts. Although a number of agents can stimulate production
of IL-1, the immunologically important inducers include antigens presented in
conjunction with MHC-II molecules and other cytokines such as IFN- and TNF. The
main effect of this stimulation is generation of IL-1 by macrophages.
Specific inhibitors of IL-1 production have been identified and appear to have
implications for the antitumor response. Corticosteroids and prostaglandins inhibit
production of IL-1 by macrophages. The production of prostaglandins by the
prostaglandin synthetase enzyme system is specifically inhibited by pharmaceuticals such
as the nonsteroidal antiinflammatory agents. Administration of these agents has reversed
inhibition of IL-1 production both in vitro and in vivo (13). Evidence exists that tumor
cells themselves produce prostaglandins and have an inhibitory effect on IL-1 (30). This
may be one of the immunosuppressive mechanisms associated with head and neck
cancer. It manifests itself as the loss of delayed hypersensitivity skin test response and
impaired in vitro cytotoxic effects, both of which are mediated in part by IL-1.
Interleukin-1 affects the cells responsible for generating an immune response against
tumor. It enhances T-lymphocyte proliferation by inducing production of IL-2 from other
lymphocytes. Proliferation of B lymphocytes and antibody production also are
augmented. Interleukin-1 also augments the cytotoxic and antigen-presenting capabilities
of the macrophages and stimulates these cells to secrete other chemoattractant cytokines,
such as IL-6 and IL-8. Further chemotactic and lymphoproliferative effects are mediated
by induction by IL-1 of the intercellular adhesion molecule on vascular endothelium,
cytotoxic T lymphocytes, and tumor cells. Interleukin-1b also generates considerable
osteoclast activation with marked bone resorption (31). Preliminary evidence shows the
possible relation of this effect to bone invasion by squamous cell carcinoma of the head
and neck (32).
Considerable redundancy is present in the actions of IL-1 and TNF. Tumor necrosis
factor- was initially described as an inducer of tumor necrosis and later found to be
cachectin. Tumor necrosis factor- was originally known as lymphotoxin. These
substances are produced by lymphocytes and monocytes in response to a number of
exogenous and endogenous stimuli, including IL-1, IFN-, and TNF itself. In addition to
promoting effects similar to those of IL-1, TNF has a more profound in vivo and in vitro
cytotoxic antitumor response (31). Interleukin-1 and TNF enhance one another's effects,
providing overlapping pathways for the immune system to mount a response.
Interleukin-2, produced by activated T lymphocytes, has a central role in the immune
response. This cytokine is essential for stimulating T-cell, B-cell, and NK-cell
proliferation and inducing lymphokine production by these effectors. Interleukin-2 is
produced after stimulation of T lymphocytes by MHC-associated antigens in conjunction
with IL-1. Secretion of IL-2 by CD4+ helper T cells responding to MHC-IIassociated
antigens appears to provide the main stimulus for activation of cytotoxic T lymphocytes
and NK cells directed against tumor cells. Secretion of IL-2 produced directly by
melanoma cells transfected with the IL-2 gene, bypassing the need for helper T cells, has
induced greater cytotoxic T-lymphocyte activity against the tumor than that against
nontransfected cells (33). Cytotoxic T-lymphocyte function still depended on antigen
presentation in conjunction with MHC-I; depletion of CD8 T cells abrogated the
antitumor response. This finding suggests that a defect in the helper T-cell arm of the
immune response with ineffective lymphokine production in the region of the tumor may
be partly responsible for the absence of an adequate cytotoxic response against malignant
cells.
The ability of IL-2 to generate effective cytotoxic cells has been used in the development
of strategies for immunotherapy. Lymphoid cells incubated with IL-2 become capable of
lysing fresh tumor cells. The cytotoxic effectors generated in this way are known as LAK
cells, which represent a class of lymphoid cells effective in the antitumor response
distinct from cytotoxic T-lymphocytes or NK cells (34,35). In addition to these effects,
IL-2stimulated lymphocytes are induced to secrete a variety of lymphokines, including
IFN-, transforming growth factor- (TGF-), IL-4, and B-cell growth factors, further
amplifying and modulating the immune response.
Other lymphokines that participate in the immune response to tumor include IL-4 and
TGF-. Interleukin-4, originally identified as B-cell growth factor, is produced by
activated T lymphocytes. Besides stimulating B-cell immunoglobulin production,
immunoglobulin isotype switching, and MHC-II and Fc receptor expression, IL-4 serves
as a potent activator of macrophages. It enhances tumor-antigen presentation and
cytotoxic ability (31). Unlike the previously discussed cytokines, TGF- is an
immunoregulatory peptide that has inhibitory effects on many of the effector mechanisms
responsible for the antitumor response. Transforming growth factor- can suppress in
vitro the mitogenic activity of IL-2 on T and B lymphocytes, NK-cell cytotoxic function,
and IL-2induced development of LAK cells (36). The importance of TGF- to the tumor
response in vivo is unknown. It is possible that this peptide functions as an endogenously
produced immunosuppressive factor. Evidence supports the presence of a soluble factor
produced by squamous cell carcinoma of the head and neck that inhibits the cytotoxicity
of LAK cells (37). Whether this factor is indeed TGF- remains to be seen.
Understanding dendritic cells is essential to understanding the response of the immune
system. Massard et al. (38) reviewed the activity of these cells. Dendritic cells originate
from the bone marrow. Their phenotype of these cells is characterized by high expression
of MHC-II molecules and high expression of ad-hesion molecules. There is a close
relation with alveolar macrophages whereby macrophages down-regulate antigen-
presenting function through TNF-. Gabrilovich et al. (39) showed that peptide-pulsed
dendritic cells isolated from tumor-bearing mice had decreased ability to induce specific
cytotoxic T lymphocytes in control animals or to restimulate immune T lymphocytes
from control mice in vitro. This reduction was reversed by means of addition of dendritic
cells from control animals. Macrophages did not improve cytotoxic T-lymphocyte
function. The dendritic cells from tumor-bearing mice did not respond and process
antigens. Gabrilovich et al. (40) achieved further correlation in an investigation of the
mechanisms of dendritic cell dysfunction under certain other conditions. Retroviral
infection appeared to down-regulate surface MHC-II molecules, which are critical in
activating an immune response.
Finkelman et al. (41) found that dendritic cells can present antigens in both a tolerogenic
or immunogenic manner. Porgador et al. (42) found that dendritic cells pulsed with
peptides outside the body can provide a protective immune response when returned to the
host. Dendritic cells harvested from peripheral blood, expanded in culture, and exposed
to exogenous agents or tumor-produced substances can elevate the level of secondary
immunosuppressive molecules.
EXOGENOUS IMMUNOSUPPRESSION
Exogenous agents given to patients with head and neck cancer (43) include alcohol
(shown to be immunosuppressive), chemotherapeutic drugs (intended to be antitumor but
may have antiimmune effects), corticosteroids (given for swelling), and the
immunosuppressive effects of surgery (which include induction of prostaglandin and
histamine, both well-known immunosuppressive agents). Viral effects due to infection
with EBV, HIV, or other agents affect both the number and function of immune cells.
The third group are immunosuppressive agents made by the immune system in response
to other immunologically active processes that can contribute to immunosuppression,
such as circulating antigen-antibody complexes.
Among the immunologically active peptides produced by tumor cells, p15e, a low-
molecular-weight retroviral membrane protein, is of distinct interest. As early as 1984,
Snyderman and Cianciolo (44) identified p15e as having an immunosuppressive effect. A
synthetic 17-amino-acid peptide homologous to a highly conserved region of several
retroviral transmembrane envelope proteins has an immunosuppressive effect similar to
that of p15e (45,46). The immunosuppressive activities include inhibition of monocyte
chemotactic responses, IL-1mediated monocyte tumor killing, the respiratory burst of
human mo-nocytes, mitogen and alloantigen-stimulated proliferation of human
lymphocytes, immunoglobulin synthesis by B lymphocytes, production of IFN-, human
NK-cell activity, and in vivo delayed hypersensitivity to sheep erythrocytes in mice. A
region similar to the conserved p15e sequence has been identified in IFN-, which may
explain some of the immunosuppressive effects of IFN-. In a study with 25 patients,
investigators in the Netherlands (45) identified different amounts of activity of p15e-like
substance and IFN- in the tumors. Immunotherapy with monoclonal antibodies against
p15e given to tumor-bearing mice in a model other than head and neck cancer markedly
improved survival rate (46).
IMMUNOTHERAPY
Methods of therapy directed at augmenting the immune response against cancer can be
classified as either active or passive. Active immunotherapy involves administration of
agents to the tumor-bearing host that elicited an immune reaction designed to control or
eradicate malignant disease. Passive immunotherapy is administration of externally
stimulated immunologic components initially obtained from the patient being treated.
These therapeutic attempts can be specific, as in the use of tumor-cell vaccines for
immunization, or nonspecific, in which immune stimulants such as bacille Calmette-
Gurin or cytokines are administered to the host. Many of these active therapeutic
manipulations were developed after clinicians observed that some patients with cancer
and severe postoperative infection had marked tumor regression and improved survival
times. The infectious agents, it is now realized, elicited broad immunologic reactions
with cytotoxic cell activation. Most of these therapies, however, have been unsuccessful
in human treatment trials. Vaccination with tumor cells or tumor cell extracts is limited
by the following factors: tumor-specific antigens are difficult to identify; malignant cells
have a considerable degree of heterogeneity; tumor cells seem capable of altering their
antigenic expression, especially for the MHC antigens; and tumors may produce
suppressive factors or augment the function of suppressor T cells, which inhibit the
immune response. These problems affect the ability of vaccines to function properly by
making it more difficult for the host response mechanisms to consistently and effectively
identify and differentiate malignant and normal cells.
Use of cytokines in therapeutic trials designed to augment the immune system has
provided a new strategy for affecting the host response to tumor. These agents have been
used alone as nonspecific active forms of therapy and in combination with other effectors
in passive approaches to tumor immunotherapy. This method of treatment is called
adoptive immunotherapy when the therapeutic agents being administered include effector
cells (47). Initial clinical attention focused on the use of the interferons and IL-2, both as
single agents and in combination with tumor-reactive lymphocytes obtained from the
patient's circulating cell pool, LAK cells, or the tumor itself, so-called tumor-infiltrating
lymphocytes (TILs).
Interferon-, IFN-, and IL-2 have been used as single agents in the management of head
and neck cancer. The clinical use of these agents has been complicated by difficulties in
establishing the appropriate antitumor and immunomodulatory dosages, routes of
administration, and evaluation of the isolated physiologic roles. Only limited antitumor
responses have been identified for these individual cytokines. Interferon- has a cytolytic
and cytostatic effect against squamous cell carcinoma of the head and neck both in vivo
and in vitro, although improvement in survival outcome after IFN- therapy has not been
found (28,29). Systemic administration has increased tumor cell differentiation and NK-
cell activity, suggesting important immunomodulatory and physiologic effects at the local
and systemic levels. Similar effects have been observed with IFN-, although the
cytotoxic effect has not been as profound for squamous cell carcinoma of the head and
neck as it has been for some of the hematologic malignant diseases. Interleukin-2 has had
antitumor and immunomodulatory effects when administered systemically or
perilesionally for squamous cell carcinoma of the head and neck (48,49). Activation of
peripheral NK cells after systemic infusion of IL-2 combined with IFN- has been
documented, and LAK cells have been generated from tumor-associated nodal
lymphocytes after regional injection of the cytokine (50,51). Interleukin-2 receptors have
been identified on some cell lines of squamous cell carcinoma of the head and neck, and
in vitro IL-2 has a direct growth-inhibitory effect on these cells (52).
Systemic administration of IL-2 as single-agent therapy has been associated with serious
morbidity and few clinical responses (53). In an attempt to improve the clinical results
obtained with IL-2 therapy, Rosenberg et al. (34), at the National Cancer Institute, used
the transfer of IL-2activated lymphocytes, which they called LAK cells, in adoptive
immunotherapy trials. Immunotherapy with LAK cells in combination with high systemic
doses of IL-2 led to marked regression of established metastatic disease in both animal
and human studies (26,34,35). Most of the experience with this form of therapy has been
in the treatment of patients with metastatic renal cell carcinoma, melanoma, and
colorectal cancer; however, investigators have evaluated this form of treatment for
squamous cell carcinoma of the head and neck. In vivo studies with nude mice have
shown marked inhibition of tumor growth of squamous cell carcinoma of the head and
neck with either local or systemic administration of LAK cells and IL-2 (52). Attempts to
generate more homogeneous populations of LAK cells with greater cytotoxic activity are
under investigation and may lead to improved clinical outcomes with decreased toxicity
(54).
The infiltration of solid tumors by lymphocytic populations has long been recognized.
The function of these cells in the control of tumor growth and dissemination is not fully
understood, but evidence suggests that the presence of a mononuclear infiltrate may be
related to improved prognosis and survival rates among patients with squamous cell
carcinoma of the head and neck (55). Methods have been developed for harvesting TILs,
and clinical trials have been instituted in which these cells are used for adoptive
immunotherapy. Treatment with TILs depends on activation of these cells by IL-2 that
results in effectors with cytolytic activity against autologous tumor. Murine studies have
shown that TILs expanded in IL-2 and transferred to animals bearing micrometastasis are
50 to 100 times more potent than are LAK cells in eradicating tumor (56,57). A clinical
trial with TIL therapy for metastatic melanoma showed marked tumor regression;
response rates were higher than those achieved with LAK cells and IL-2 (58). Similar
results have been obtained in vitro for cultures of squamous cell carcinoma of the head
and neck, and isolation and activation of TILs from a patient with head and neck cancer
has been accomplished (48,49). The cytolytic specificity exhibited by TILs toward
autologous tumor results from MHC restriction. Tumor-specific antigens exposed to
dendritic cells harvested from peripheral blood of patients and expanded in vitro has been
proposed as a form of immunotherapy, but no data are available for patients with head
and neck cancer. This specificity makes this form of immunotherapy appealing, but
further investigation is needed to determine the effectiveness in the management of head
and neck cancer.

HIGHLIGHTS
A cancer progression model specific for head and neck cancer
is being developed. This accounts for the multistep process of
genetic alterations responsible for the pathogenesis of
malignant tumors.
Mutation of p53 appears to have a central role in the
development of cancer by altering the ability of cells to respond
to DNA damage.
Human papillomavirus proteins interact with p53; the result is
inactivation of p53 protein.
Immunoglobulin-associated cytotoxicity directed against
malignant cells occur through two mechanismscomplement
fixation and antibody-dependent cellular cytotoxicity.
Interferon- may prove useful as an immunotherapeutic agent
because of its cytotoxic, immunomodulatory, and cell-
differentiating effects.
Tumor production of immunosuppressive factors may impair
the cytotoxic response by inhibiting the immuno-modulatory
effects of the cytokines.
Interleukin-1 may have a role in the development of bone
invasion by squamous cell carcinoma of the head and neck.
Defects in the helper T-lymphocyte phase of the immune
response may be partly responsible for the impaired cytotoxic
response against malignant cells.
Active immunotherapy for cancer involves administration of
agents that can elicit an immune response, such as IFN-.
Passive immunotherapy involves administration of externally
stimulated immunologic components such as LAK cells,
initially obtained from a tumor-bearing patient.
Systemic and perilesional injection of IL-2 for squamous cell
carcinoma of the head and neck has activated NK and LAK
cells, but no survival benefit has been shown.
Adoptive immunotherapy with IL-2stimulated LAK cells or
TILs may improve the rates of tumor regression and control.
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

103 CUTANEOUS MALIGNANCY
Head & Neck SurgeryOtolaryngology
103




CUTANEOUS MALIGNANCY
FRED J. STUCKER
CHERIE-ANN O. NATHAN
TIMOTHY S. LIAN

F.J. Stucker, C-A. O. Nathan, and T.S. Lian: Department of
OtolaryngologyHead and Neck Surgery, Louisiana State University
Medical Center, Shreveport, Louisiana.


Skin cancer is the most common human malignancy, with more than 800,000 cases in the
United States annually (1). Most tumors arise on the sun-exposed regions of the head and
neck. Basal cell carcinoma is the predominant histologic type and accounts for about 90%
of all cutaneous neoplasms in the head and neck region. Second in incidence is squamous
cell carcinoma. The least common form is melanoma, which accounts for approximately
7,300 deaths each year in the United States. There are 2,000 additional deaths related to
other forms of cutaneous cancer (2). Cutaneous malignancies are classically divided into
epidermal, dermal, adnexal, and melanocytic. Malignant melanoma has a distinct biologic
behavior and is addressed separately in Chapter 102. Many other rare skin malignancies
of the dermis and adnexa are not discussed specifically, but some principles of evaluation
and treatment of cutaneous cancers are applicable. This chapter is primarily dedicated to
a discussion of basal cell and squamous cell carcinomas, their precursors, and associated
epidermal neoplasms.
RISK FACTORS
Risk factors for basal and squamous cell carcinomas are strikingly similar. These lesions,
although seen in younger age groups, are most often encountered in patients 60 years of
age or older.
The mechanism by which ultraviolet light causes sun-damaged skin has been extensively
studied. Laboratory experiments indicate that the wavelengths with the most potential for
carcinogenesis are those in the range of 280 to 320 nm, the ultraviolet B band. This
ultraviolet B is responsible for the common sunburn. The transition from normal to
actinic (i.e., sun damaged) to cancerous skin is usually a progressive process that occurs
over several decades.
With the current environmental changes occurring with the earth's protective ozone layer,
the concern for skin cancer becomes much more significant. A dramatic ozone depletion
above the Antarctic continent has been detected (3). For each 1% reduction in
atmospheric ozone concentration, there is a concomitant 2% increase in ultraviolet B
penetration (4).
The carcinogenesis of epidermal tumors parallels the multistep development of other
neoplasms. As with other neoplasms, certain characteristics render the host more
susceptible to the development of cancer. Traits that are associated with an increased
incidence of skin cancer include fair complexion, light hair, blue or green eyes, inability
to tan, propensity to sunburn, history of multiple or severe sunburns, and Celtic ancestry
(5). Other factors implicated include age, occupation, habits (tanning booths), and
residential geography, which are considered indirect causes of increased sun exposure.
The bulbs used in tanning booths are almost exclusively ultraviolet A wavelength and are
promoted as providing a safe suntan. However, recent evidence indicates that ultraviolet
A (320 to 400 nm) synergistically augments ultraviolet B re-sponses and is independently
capable of producing deleterious skin alterations and neoplasias (6).
Other etiologic factors are associated with the development of cutaneous carcinoma (5).
Chronic exposure to chemical agents, such as arsenic in patients treated with Fowlers
solution, has been associated with the development of multiple squamous and basal cell
tumors. Patients with chronic ra-diodermatitis, resulting from superficial radiation
therapy, demonstrate a propensity to develop multiple and aggressive lesions. Trauma in
the form of burns, ulcers, and scars is also associated with the development of skin cancer
(i.e., Marjolins ulcer). Immunosuppression, common in transplant patients and patients
with leukemia or lymphoma, can be complicated by an increased incidence or
aggressiveness of skin malignancies.
Studies of human papillomavirus offer additional support for the importance of immune
dysfunction in the development of skin squamous cell carcinoma. One study showed
human papillomavirus presence in 60% of cutaneous squamous cell carcinoma lesions
found in renal autograft recipients. Moreover, this human papillomavirus presence was
significantly higher than that found in matched transplant recipients without cutaneous
malignancy (7). There also appears to be a high incidence of human papillomavirus in
squamous cell carcinoma lesions of the cervix, penis, and digits (8).
Genetic syndromes, such as xeroderma pigmentosum (autosomal recessive) and nevoid
basal cell carcinoma syndrome (autosomal dominant), are associated with a predilection
for developing multiple basal cell carcinomas, often at an early age.
BASAL CELL CARCINOMA
Evaluation
There are several clinical types of basal cell carcinoma. Smith (9) outlined five clinical
forms: nodular or noduloulcerative, morphealike or sclerosing, superficial multicentric,
pigmented, and fibroepithelioma. Although other less common types exist,
subclassification is not clinically useful. The most common type is the nodular or
noduloulcerative lesion. This lesion typically presents as a discrete, raised, circular lesion
that appears pink and waxy, with a capillary network that is easily visible. There is often
an area of central ulceration, and the border of the lesion is rolled. This is the type of
basal cell carcinoma that is easiest to recognize and treat. A variant of this lesion is cystic
basal cell carcinoma, which is also waxy and well demarcated but is more cystic in
appearance.
The superficial basal cell carcinoma lesion shows evidence of scarring and atrophy, with
a threadlike waxy border. This lesion may consist of one or several red scaling patches.
These crusted lesions have irregular borders and gradually increase in size by peripheral
extension. They are relatively uncommon in the head and neck and more frequently occur
on the trunk or extremities.
The most dangerous clinical form of basal cell carcinoma is the morphea type, also called
sclerosing or fibrosing basal cell carcinoma. This variety is typified by its macular,
whitish, or yellowish plaque. Some physicians have noticed an increased incidence
among women. The margins may be quite indistinct, and the lesion may go unnoticed for
years in some patients. Complete excision is difficult because of ill-defined margins. The
lesion may look like a scar, may develop telangiectasia, or may ulcerate.
A less common basal cell carcinoma variant is pigmented basal cell carcinoma, which is
characterized by its brown pigmentation and may resemble a pigmented nevus or a
melanoma. The appearance and behavior of this lesion seems to parallel that of nodular
basal cell carcinoma. Pigmented basal cell carcinoma differs from the noduloulcerative
type only by the brown pigmentation of the lesion. This type of lesion may also be
mistaken for seborrheic keratosis, melanoma, or dermatofibroma.
Fibroepitheliomas, another variant, present as firm pedunculated lesions that resemble
fibromas. It was first described in 1953 by Pinkus (10). These lesions commonly occur on
the back.
The nevoid basal cell carcinoma syndrome is an autosomal dominant disease. During
childhood, small cutaneous nodules appear, often numbering in the hundreds. These
lesions initially have a rather indolent course during the nevoid phase, but as the patient
ages, a neoplastic phase may occur in which the lesions show a marked change in
aggressiveness. The lesions become invasive, destructive, and mutilating. Abnormalities
associated with nevoid basal cell carcinoma syndrome include jaw cysts, bifid ribs,
scoliosis, mental retardation, and frontal bossing.
Histopathology
The characteristic cell in basal cell carcinoma has a large, oval, or elongated nucleus with
relatively little cytoplasm. These cells may resemble the basal cells of the epidermis, but
the neoplastic forms lack intercellular bridges. The nuclei are rather uniform in size and
configuration. A connective tissue stroma proliferates with the tumor and is oriented in
parallel bundles around the tumor masses, causing peripheral palisading of the cells and
stromal retraction. This is commonly referred to as peritumoral lacunae. The stroma is
often mucinous. Because mucin shrinks with dehydration and fixation of the specimen,
the stroma may show retraction from the tumor islands. This detachment of tumor islands
from the stroma is known as clefting and is a helpful diagnostic sign.
Lever and Schaumburg-Lever (11) divided basal cell carcinoma into four basic histologic
patterns: solid, keratotic, cystic, and adenoid. In the solid pattern, the cells show no
differentiation. This type generally displays tumor masses of various sizes and shapes
embedded in the dermis (Fig. 103.1). The peripheral cell layer may show a palisading of
the nuclei. Basal cell carcinomas that differentiate toward hair structures are referred to as
keratotic. This lesion is typified by undifferentiated cells in combination with
parakeratotic cells and horn cysts (Fig. 103.2). Cystic tumors show differentiation toward
sebaceous glands. Histologically, there may be one or several cystic spaces within the
tumor lobules. In the adenoid variety of basal cell carcinoma, the tumors display a tubular
or glandular formation. The strands of epithelial cells commonly form a lacelike pattern
(Fig. 103.3).

FIGURE 103.1. Basal cell tumor masses (solid type).



FIGURE 103.2. Undifferentiated cells with parakeratotic
and horn cysts (keratotic type).



FIGURE 103.3. Lacelike patterns of epithelial cells
(adenoid type).



KERATOTIC BASAL CELL CARCINOMA
Keratotic basal cell carcinoma, also known as basosquamous cell carcinoma or
metatypical carcinoma, has been the subject of much controversy. The confusion arises
because histologically there are coexistent features of both basal cell and squamous cell
carcinomas in the same lesion, frustrating accurate assessment of prognosis and behavior.
Most dermatopathologists currently believe that basosquamous tumor is a variant basal
cell carcinoma, referred to by many as keratotic basal cell carcinoma (11). Although there
is limited potential for metastasis, keratotic basal cell carcinoma is thought to be more
biologically aggressive than many of the other types of basal cell carcinomas.
SQUAMOUS CELL CARCINOMA
Evaluation
Far less common than basal cell carcinoma, squamous cell carcinoma accounts for
approximately 10% of skin malignancies. As with its counterpart, basal cell carcinoma,
squamous cell carcinoma is related to chronic (i.e., 10 to 20 years) sun exposure. As the
equator is approached, the relative incidence of squamous cell carcinoma increases
compared with basal cell carcinoma. Cutaneous squamous cell carcinoma, like basal cell
carcinoma, is more common in men.
Squamous cell carcinoma of the skin usually presents as an erythematous, ulcerated,
crusting lesion. The tumor often demonstrates a granular base that may be friable and
tends to bleed with minimal trauma. There is usually an elevated area of induration at the
lesion edge, and there may be an inflammatory response in the adjacent tissues.
These lesions present in different patterns. Squamous cell carcinoma can present as a
thickened hyperkeratotic patch or an area of crusting. Under this crust is an ulcerated
base with a rolled margin. Other lesions may be recognized as areas of persistent
ulceration, possibly in the site of previous trauma, burns, or an old scar (i.e., Marjolins
ulcer). Neoplastic change in a chronic ulcer may result in basal cell or squamous cell
carcinoma and is associated with a poorer prognosis and higher rates of metastasis.
Superficial multifocal lesions can arise in actinic skin. These lesions are usually
accompanied by a scaling patch that bleeds with minimal trauma. Diagnosis and
determination of the extent of the lesion can be difficult, and multiple biopsies may be
necessary.
Squamous cell carcinoma occasionally presents as a nodular exophytic lesion. Initially
cystic, it later tends to become ulcerative and progressively enlarges. These lesions may
also demonstrate a sudden growth spurt (12).
Histopathology
Several histologic characteristics are important in analyzing squamous cell carcinoma.
The usual histologic picture of squamous cell carcinoma of the skin is that of irregular
masses of epidermal cells that proliferate downward and invade the dermis. The tumor
masses may be well differentiated or may show atypical or anaplastic cells. The
differentiated tumors tend to be associated with evidence of keratinization, such as
keratin pearls. Tumors are graded from 1 to 4 using Broders classification; grade 1
tumors are well differentiated, and grade 4 tumors are poorly differentiated.
Some squamous cell carcinomas are actinically induced, and some arise de novo. Lesions
arising in sun-exposed areas appear to follow a more benign course with a low incidence
of metastasis. The de novo lesions are more aggressive in their behavior and exhibit
greater potential for metastasis. One researcher estimated that at least 8% of patients with
de novo lesions develop regional or distant metastases (13). It is often possible to
differentiate clinically between the two types of squamous cell carcinoma. Histologically,
a determination can usually be made by looking for actinic changes in the skin adjacent
to the squamous cell carcinoma.
Squamous cell carcinoma has metastatic potential, and regional metastatic spread is
correlated with depth of invasion. Squamous cell carcinoma lesions that penetrate to
Clarks level IV or V are associated with a 20% regional metastatic rate.
Histologic variations of squamous cell carcinoma are categorized as generic, adenoid,
bowenoid, verrucous, and spindle-pleomorphic types (14). The generic type is
characterized by actinic changes. In the adenoid type, there is a pseudoglandular
arrangement. These tubular or alveolar formations result from dyskeratosis and
subsequent acantholysis. The lumina are lined with one or several layers of epithelium
and are filled with desquamated acantholytic cells. The bowenoid type of squamous cell
carcinoma is characterized by evidence of invasion coexistent with the findings of
Bowens disease.
Verrucous carcinoma is seldom seen as a skin neoplasm on the head and neck, but it is
well known as a tumor of the oral cavity and larynx. It presents as a white cauliflower-
like lesion. The tumor is well differentiated, demonstrating hyperkeratosis, parakeratosis,
and acanthosis. Clinical and pathologic correlations are needed to confirm the diagnosis.
In the spindle-pleomorphic type of squamous cell carcinoma, there is little evidence of
differentiation. These tumors are anaplastic, show little or no keratinization, and are
usually considered to be a Broders grade 4 tumor. The spindle cells are intermingled with
collagen, may be arranged in whorls, and can be associated with pleomorphic giant cells.
PREMALIGNANT LESIONS
Several skin lesions are considered premalignant. This group includes a low-grade
malignancy that can be treated as if it was a premalignant lesion. The most common of
these are actinic keratosis, Bowens disease, and keratoacanthoma.
Actinic Keratoses
Actinic keratoses (i.e., solar keratoses or senile keratoses) is the most common
premalignant lesion of the head and neck and is seen almost exclusively in sun-exposed
areas of the skin. The lesions are generally less than 1 cm in diameter and are commonly
located on the face, scalp, hands, and forearms (Fig. 103.4). They are considered
precancerous. The chance of progression to epidermal cutaneous carcinoma has been
estimated to be as great as 20% (11). They usually present as an erythematous patch,
often covered by an adherent scale. Clinically, they show little or no sign of
inflammation. Occasionally, there is a marked hyperkeratosis, giving the appearance of a
cutaneous horn. A sandpaper-like scale is the most distinctive feature on clinical
examination. Because these lesions have malignant transformation potential, most
physicians believe they should be treated. Depending on the clinical setting, superficial
shave excision, cryosurgery, topical treatment with 5-fluorouracil, or trichloroacetic acid
peel may provide effective treatment. The differential diagnosis includes seborrheic
keratosis, benign lentigo, squamous cell carcinoma, and basal cell carcinoma.

FIGURE 103.4. Actinic keratosis on forehead.



Bowens Disease
Bowens disease is considered a preinvasive form of squamous cell carcinoma. It can be
considered synonymous with carcinoma in situ of the skin. Histologically, there is full-
thickness dysplasia of the epidermis without evidence of invasion. Clinically, the lesion
presents as a well-circumscribed, erythematous, scaly patch or plaque with an irregular
border. As with squamous cell carcinoma, these lesions generally occur in sun-exposed
areas. They are particularly common in patients with a history of chronic arsenic
ingestion, in whom lesions often occur on nonexposed skin. The lesion may resemble a
superficial basal cell carcinoma, but it lacks the fine pearly border.
Keratoacanthoma
Keratoacanthoma is a benign usually self-limited epithelial tumor that is easily confused
clinically and histopathologically with squamous cell carcinoma. It is more common in
males and typically presents in older patients. There is a history of rapid growth, usually
over 2 to 6 months. The lesion begins as a smooth rounded nodule, but with further
enlargement the center becomes ulcerated and filled with keratinous material, taking on a
volcano-like appearance. The hallmark of keratoacanthoma is rapid growth over weeks or
months.
The most common site affected is the nose. Although histologically the lesion resembles
a squamous cell carcinoma (Fig. 103.5), it may involute spontaneously, leaving only a
depressed scar. Because of the lack of predictability, surgical excision is recommended.

FIGURE 103.5. A: Keratoacanthoma of the auricle. B:
Histologic volcano-like appearance.



PROGNOSIS
Tumor Behavior
Tumor histology, local extent or infiltration, tumor size, anatomic site, associated risk
factors (e.g., age, prior irradiation, genetic syndromes), and previous treatment must be
considered in determining the risk of recurrence for a given lesion. We consider the risk
factors shown in Table 103.1 to be indications for histologic documentation of tumor-free
margins.

TABLE 103.1. FACTORS ASSOCIATED WITH
HIGH-RISK CUTANEOUS MALIGNANCIES



The clinical and histologic types are significant prognostic variables. The morphea type
of basal cell carcinoma is well known for its subversive attitude. This lesion generally
spreads centrifugally by way of fingerlike projections of tumor. It is deceptive in its
behavior and can be difficult to evaluate and control. Keratotic (i.e., basosquamous),
recurrent basal cell, and spindle cell variants of squamous cell carcinomas are also
associated with worse prognoses.
Squamous cell lesions can be virulent. They have the potential to metastasize to regional
nodes and are sometimes associated with distant metastases. Locally, these tumors are
more likely to grow in a vertical fashion and less likely to respect the barriers of cartilage
and bone than basal cell carcinoma. It is prudent to evaluate the regional lymphatic
drainage when dealing with squamous cell carcinoma.
The anatomic location influences the prognosis because various regions of the head and
neck have a propensity for tumor recurrence. Lesions on the nose and ear have higher
rates of recurrence, which is probably associated with embryonic fusion planes (15).
These embryologic sites of fusion afford greater access for tumors, which use the planes
as avenues for spread. The most prominent sites are the preauricular and postauricular
regions, the floor of the nose and columella, and the nose-cheek crease. The periorbital
region is also at risk for tumors tracking along the bone or periosteum, particularly in the
medial canthal region. Mohs (16) speculated that basal cell tumor cells migrate along the
periosteum or perichondrium of the nose and the medial canthi because of the close
apposition of the skin to the bone and cartilage in these locations.
Swanson (17) determined that the high-risk sites fall within an H zone on the face (Fig.
103.6). In highlighting the specific regions at risk, he cited the junction of the ala with the
nasolabial fold, the nasal septum, the nasal ala, the inner canthi and lower eyelids of the
periorbital region, the periauricular region extending to the temple, and certain scalp
lesions.

FIGURE 103.6. H zone: high-risk areas of aggressive
cutaneous malignancies. (From Swanson NA. Mohs
surgery: technique, indications, applications, and the
future. Arch Dermatol 1983;119:761, with permission.)



Recurrent Cutaneous Lesions
A recurrent carcinoma of the skin presents a much more challenging problem than the
primary lesion. Recurrent cancer indicates inadequate initial therapy or a persistence of
disease in the tissue adjacent to the original lesion. Levine and Bailin (18) evaluated 496
cases of recurrent basal cell carcinoma in an attempt to identify significant risk factors.
They found the midface region was involved in 57.6% of the cases and the auricular and
preauricular areas accounted for 13.4% of the recurrences. The nose is the most common
location of recurrence (25.5% to 41%). The relative risk for recurrence was calculated in
one study for different locations (19). In order of decreasing magnitude of risk, the
locations are the nose (2.38), the ears (1.43), the periorbital areas (1.17), the remainder of
the face (1.04), and the neck and scalp (0.55). The distribution of these recurrent tumors
is shown in Fig. 103.7.

FIGURE 103.7. Distribution of recurrent cutaneous
malignancies.



Jackson and Adams (20) described 33 cases of horrifying basal cell carcinoma. These
lesions were large (greater than 3 cm), destructive, locally uncontrollable, or metastatic.
In defining the predominant characteristic of each lesion, the researchers found that 18
were large, 6 destructive, 5 locally uncontrollable, and 4 metastatic. They concluded that
these horrifying tumors usually had an onset before age 40 and recurred more than twice
despite adequate treatment and that each recurrence appeared sooner and became larger
than the preceding tumor. In many patients, underlying conditions predisposed them to
cutaneous basal cell carcinoma, including arsenic ingestion, nevoid basal cell syndrome,
preexisting burns, and radiodermatitis.
Levine (21) studied the pathogenesis and treatment of large recurrent cutaneous
neoplasms. The advanced lesions, called massive or previously uncontrolled, met one or
more of the following criteria: diameter greater than 3 cm, involvement deeper than skin
and subcutaneous fat, four or more previous treatments without control, or proven
metastatic disease.
MANAGEMENT
An advantage of nonsurgical management of primary skin malignancies is cure rates
reported in excess of 95% for selected skin malignancies. These nonsurgical modalities
use field therapy for their mechanism of treatment. Skin cancers grow both radially and
vertically in a predictable and proportional manner. Field therapy uses these growth
characteristics to treat a defined area containing both tumor and a surrounding layer of
normal tissue.
Curettage with Electrodesiccation
The most common treatment for basal cell carcinoma is curettage excision combined with
electrodesiccation, also known as electrosurgery or electrodesiccation with curettage. It is
used primarily by dermatologists, who manage most of these lesions, and is quite
successful when used appropriately, yielding cure rates of 92% to 98% (22).
The rationale for using this modality is that basal cell and squamous cell tumors have a
soft feel that can be detected as a lesion is curetted. In experienced hands, this allows the
removal of all palpable tumor with different sizes of curettes. After normal-feeling tissue
is encountered over the entire base of the excision, electrodesiccation or fulguration of
the wound is performed. This process is completed from two to six times, and the wound
is treated topically and allowed to heal by second intention.
The advantages of electrosurgery include maximal sparing of normal tissue, ease of
performance, and expediency (23). The disadvantages include care of an open wound,
depressed or hypertrophic scarring, and delayed bleeding. Electrosurgery should be used
only in selected lesions, usually basal cell lesions less than 2 cm in diameter.
Contraindications for this treatment modality include lesions with deep invasion,
morphealike and sclerotic basal cell carcinomas, and recurrent tumors (22). If squamous
cell tumors are treated by this modality, they should be carefully selected.
Cryosurgery
Cryosurgery is another treatment option that may be appropriate for some basal cell
lesions. As with electrosurgery, the skill and experience of the treating physician are
critical. The most common cryogen used is liquid nitrogen. A temperature of at least
30C is considered to be lethal to cutaneous malignant tissue, although some surgeons
consider 50C to be more appropriate. The tumor and an area of surrounding tissue are
frozen to ensure the adequacy of the ablation. A thermocouple inserted at the margin of
the treatment area ensures that the proper temperature for cell killing is reached. The
tissue is allowed to thaw, and after an appropriate period, the freeze-thaw cycle is
repeated.
Proponents of this technique cite as advantages its high cure rate, tissue-sparing
capabilities, and expedience (24). It is thought to be useful in tumors overlying cartilage
that can be frozen without undergoing necrosis. It may be particularly useful in patients
with multiple lesions. The disadvantages include a prolonged healing phase and wound
care. Hypopigmentation and unsatisfactory scarring can occur. Its use should be limited
to lesions with well-defined borders and should not be used for morphealike tumors or
recurrent skin cancers.
Radiation Therapy
Radiation therapy has the capability of curing most skin cancers successfully and has
been used extensively in the past (22). As more expedient and less radical methods of
treatment have become popular, its use in recent years has waned. The advantages of
irradiation include the ability to treat a wide field of tumor and avoidance of surgery. The
disadvantages include the protracted treatment course, expense, adjacent tissue effects,
limited effectiveness if tumors involve cartilage or bone, and the possibility of
radiodermatitis and delayed carcinogenesis. Although many of these problems have been
overcome with the refinements and advances in technology, this modality provides
overtreatment for most skin cancers. Radiation therapy is currently used in the treatment
of poor operative candidates, as an adjuvant to surgery, or for palliation in advanced
lesions. It can be curative, but careful selection of lesions and patients is crucial.
Photodynamic Therapy for Cutaneous Malignancy of the Head and Neck
Photodynamic therapy (PDT) is a therapeutic modality using a photosensitizing drug that
selectively localizes in tumors and that, on being activated by exposure to light, causes
preferential tumor necrosis. Despite its initial promise, PDT remains an investigational
modality at the present time. The two components needed for this therapy are a
photosensitizer drug and a laser to activate the drug. The most widely used drug in head
and neck has been porphyrin. Some of the other drugs that have been used as
photosensitizers are tetracyclines, fluorescein, rhodamine, and more recently sulfonated
metallophthatlocyaines. The light source consists of a laser either delivered down a fiber
for surface illumination (which is the technique of choice for superficial cancer) or
implanted into the substance of the tumor (used for bulky tumors). The argon ion dye
pumped laser is most commonly used in North America.
Review of the literature reveals that initially this treatment was used predominantly for
palliation of advanced skin cancer. Most series reveal a dramatic initial response in many
patients, but long-term follow-up was rarely possible because of the advanced nature of
these cancers (25). The response was variable and unpredictable, and severe pain and
skin necrosis were common. A major problem in evaluating the literature is the
tremendous variability in technique, drug, and light dosage in the reported series.
The advantages of PDT are that multiple lesions can be treated at the same time, it has
good cosmetic results, and no anesthesia is required. The disadvantages include lack of
predictable response in more advanced lesions and occasional photosensitivity. Once the
technique has been further refined, it has great potential in the management of skin
cancers.
Interferon-
Interferon- (IFN-) is under investigational use for the treatment of primary skin
cancer. Pilot studies demonstrated that basal cell carcinoma of the nodular and superficial
types shows excellent responses (26,27). Treatment is initiated with low-dose (1.5 106
IU) intralesional IFN- three times a week. Local reactions include pain and persistent
erythema. The most common side effect is a flulike illness, the symptoms of which
respond to acetaminophen. Hematologic side effects include leukocytopenia and
thrombocytopenia.
The mechanism is believed to be due to the antiproliferative and immunomodulating
properties of interferon. Through a nonspecific stimulating effect on macrophages and
natural killer cells, localized administration of IFN- focally increases the host response
to the neoplastic tissue.
Excisional Surgery
Surgical excision for cutaneous neoplasms is the modality with which most head and
neck surgeons have the most experience. The success rate for this method of treatment is
93% to 95% (28). The major advantages of excisional surgery include the ability to
obtain tissue for diagnosis and to assess the completeness of excision. By use of frozen
sections, the surgeon can evaluate the margins of excision histologically. Another benefit
is the excellent cosmesis, particularly if defects are amenable to primary closure. The
disadvantages are that excisional surgery can be more time consuming, inconvenient, and
expensive for the patient than other treatments. Most surgeons believe that the histologic
confirmation of the adequacy of excision outweighs these relatively minor disadvantages.
The carbon dioxide (CO
2
) laser can also be used for excision of cutaneous carcinomas.
Mohs' Surgery
Mohs pioneered a new technique for removal of cutaneous neoplasms while he was a
medical student in the 1930s. His first results were published in 1941, and the new
modality was dubbed chemosurgery technique (29). With this method, zinc chloride paste
(a chemical fixative) was applied to the cancer, fixing it in situ and permitting careful
serial excisions with examination of the entire specimen histologically. This permitted
him to map extensions of residual tumor, so that reexcision of these pockets of cancer
were possible. The cure rates associated with the technique range from 96% to 99%
(29,30). Tromovitch and Stegman (31) revised the original technique and used a fresh-
tissue technique that adhered to the same tenets of serial excisions and mapping of
residual tumor deposits. The nomenclature for the techniques has now evolved to the
point that Mohs' chemosurgery implies a fixed tissue technique and Mohs' micrographic
surgery indicates use of the fresh-tissue technique. Most dermatologic surgeons now use
the fresh-tissue technique, commonly called Mohs' surgery. Details of the technique are
published in numerous sources (17,28,31). A schematic of this process is shown in Fig.
103.8.

FIGURE 103.8. Schema used by micrographic cutaneous
tumor excision. (Modified from Mohs FE.
Microcontrolled surgery for skin cancer. In: Epstein E,
Epstein E, eds. Skin surgery. Philadelphia: W.B.
Saunders, 1987, with permission.)



The advantages of Mohs' surgery lie in its ability to examine the resection margins in
their entirety, unlike routine or frozen-section margins that evaluate a random sampling
of margins. Microscopic foci of tumor can be identified, mapped, and reexcised with this
technique. It also allows removal of the neoplasm with maximal preservation of
surrounding normal tissue. Another benefit of the Mohs' fresh-tissue technique is the
ability to immediately reconstruct the defects that have been created. The major
advantage is that this technique has the highest cure rate in the management of advanced,
high-risk, or recurrent lesions. Mohs' surgery is most useful in the high-risk lesions
characterized in Table 103.2. The disadvantages of the Mohs' technique are the special
expertise, time, and expense involved. Someone with this special training may not be
available in all communities. These drawbacks are compensated for by achieving a
disease-free status.

TABLE 103.2. TREATMENT BASAL CELL
CARCINOMA



Carbon Dioxide Laser
Laser excision is appropriate in the management of some skin malignancies. It is
indicated instead of standard excision for patients whose cardiac status or other medical
conditions render it unwise to use epinephrine in the local anesthesia. Lidocaine without
the addition of a vasoconstrictor has a duration of approximately 15 minutes, more than
adequate time for the few minutes required to resect most facial lesions in a bloodless
fashion with the CO
2
laser. If margins are positive, more anesthesia is infiltrated where
required and more tissue removed as needed. After margins are determined to be free of
tumor, the area of the local flap is infiltrated and the reconstruction carried out. We have
also found laser excision to be of benefit in patients with bleeding disorders.
Another indication for use of the CO
2
laser is the resection or vaporization of small
multiple lesions that then require no reconstruction. Lesions as large as 7 to 8 mm can be
resected bloodlessly and are left with a physiologic dressing that heals completely within
10 days, resulting in excellent cosmesis. This method is particularly effective in
managing multiple premalignant or potentially malignant lesions in patients with skin
cancer.
Palliation of the neglected lesion in the very elderly or debilitated patient whose skin
cancer is of less concern than more major health considerations is carried out with
alacrity using the CO
2
laser. These patients often reside in limited-care facilities, and
palliation can be directed toward improved nursing care, better patient comfort, and
convenience. These goals prompt some type of treatment, although cure may not be
realistic or possible (Fig. 103.9). Our approach to management techniques is summarized
in Table 103.3.

FIGURE 103.9. A: Multiple basal cell cancers palliated
with laser. B: Six weeks after laser ablation.



TABLE 103.3. TREATMENT CUTANEOUS
MALIGNANCIES



SURGICAL RECONSTRUCTION
There are three fundamental methods of managing the defects created by excisional
surgery for skin cancer: no reconstruction, immediate repair, or delayed reconstruction.
The first alternative is used if the wound is allowed to heal by second intention or is
covered by a graft and the subsequent defect not reconstructed. This may be appropriate
for patients who are palliated or who for other reasons are not candidates for
reconstruction. Other patients may be candidates or better served with a prosthesis. The
surgeon's choice is influenced by many factors, such as the general health of the patient
and his or her life expectancy. The location and extent of the lesion and the social
situation of the patient may play a role in the decisions concerning reconstruction. Large
defects are of little concern to some people, but a minimal defect can be devastating to
others.
Functional restoration takes precedence over cosmesis if this choice must be made (e.g.,
reconstruction of the upper lip to ensure a competent oral sphincter before embarking on
a nasal reconstruction). Early reconstruction of nasal ala and eyelid defects is of
paramount concern because reconstruction after contracture has occurred is rarely
satisfactory.
In addition to functional restoration, anatomic, pathologic, and cosmetic considerations
influence the surgeons choice of reconstructive method. Basic to any flap reconstruction
is the secondary tissue deficit that, when closed, results in increased tension on the
surrounding local tissue. Scar contraction has the potential to distort and create a greater
deformity. The use of a skin graft decreases this likelihood by harvesting tissue where
there is an abundance, usually some distance from the defect, and substituting this tissue
for the resected tumor.
Anatomic considerations control surgical options by imposing constraints such as
symmetry, facial landmarks and structures, and the lack of availability of adequate local
or adjacent tissue. All flaps create a secondary defect that must be attended to in some
manner. This is most often done by primary closure, but the surgeon can use another flap
or a graft.
Pathologic considerations influence reconstructive choices. The defects related to certain
histologic tumor types might best be covered with a skin graft rather than have potential
tumor hidden by a thick flap. Questionable margins are another factor that might prompt
a more conservative choice. Tumors located in areas known clinically to be more virulent
(e.g., medial canthus, nasal spine, external ear canal) might best not be reconstructed with
a thick flap. Squamous cell carcinomas of the skin are usually more aggressive and
infiltrative than basal cell carcinomas, and this affects their management. An exception to
this is the morphea type of basal cell carcinoma, which is infiltrative. Its iceberg-like
subdermal extension may make elaborate reconstructive efforts futile and perhaps
devastating for the patient. It is wise to defer immediate reconstruction and allow healing
by second intention or cover the defect with a skin graft. When the recipient bed has a
marginal blood supply, delayed skin grafting is recommended. The wound area is
allowed to granulate for 21 days. Then a 1- to 2-mm circumferential strip is removed,
followed by cross-hatching of the area. A thick (0.45 to 0.5 mm) split-thickness skin graft
is placed. If further reconstruction is needed, it can be undertaken when the patient is
confirmed to be tumor free, usually after a period of observation of 1 to 2 years.
Planning Reconstruction
In designing local flap reconstruction, the surgeon must first consider the effects on
adjacent tissues and structures. It is essential that the tissue to be moved into the defect is
lax and abundant enough to close the surgical void. The donor site must also be closed,
usually primarily, without unacceptable consequences to adjacent tissues or structures.
Utmost in the surgeons mind must be the placement of incisions. Closure lines should be
in skin creases, facial structural demarcations, or relaxed skin tension lines. The tension
and direction of maximal pull must not distort, create asymmetry, or result in an
unacceptable scar. The ultimate contracture of the resulting scars should not create a
deformity.
A review of our surgical cases indicates that the most common management after
resection is advancement and primary closure. Obviously, this technique is propitious for
most small lesions. For those requiring a more sophisticated form of reconstruction, there
are several reliable reconstructive options (Table 103.4). Reconstruction options and
techniques are discussed in Chapter 162, Chapter 166, and Chapter 169.

TABLE 103.4. METHODS OF RECONSTRUCTION



COMPLICATIONS
In dealing with facial cutaneous malignancies, the temptation to avoid disfigurement is
great (Table 103.5). Unfortunately, this often results in an inadequate excision, dooming
the patient to recurrence and quite possibly a much worse prognosis. Perhaps the most
important lesson that the Mohs' technique has taught us is the insidious behavior of some
cutaneous malignancies. Therefore, margins must always be checked and histology
confirmed. Questionable margins should not be reconstructed.

TABLE 103.5. COMPLICATIONS
CUTANEOUS MALIGNANCIES



What may originally be considered a simple excision is occasionally complicated by
positive margins. The surgeon must be flexible. If the patient is under local anesthesia,
general anesthesia may be needed. If the patient was not aware of the extent of the
resection and subsequent repair, the surgeon should stage the surgery and discuss with the
patient what may be involved. In considering reconstruction, function is always more
important than cosmesis. The surgeon should avoid designing flaps that adversely affect
function (i.e., cheek flap producing ectropion).
In dealing with squamous cell carcinoma, local and regional lymph nodes must be
carefully evaluated. For lesions larger than 3 cm, staged neck dissections or adjuvant
therapy should be considered. It is mandatory to follow all patients with cutaneous
malignancies, and biopsies should be performed for suspicious areas. In many patients
with skin cancers, constant vigilance is the key to a successful outcome.

HIGHLIGHTS
Sun exposure is associated with all forms of
skin cancer.
Unlike other forms of basal cell cancer, the
morphea type is particularly difficult to
excise because of indistinct margins, skip
lesions, and a propensity for deep invasion.
De novo squamous cell cancer tends to be far
more aggressive locally and metastatically than
cancer that develops after actinic changes.
Histology, anatomic site, and primary or
recurrent status should be considered in
managing a cutaneous malignancy.
Premalignant and low-grade lesions can be
managed by chemotherapy (i.e., 5-fluorouracil),
electrodesiccation and curettage, or CO
2
laser.
All other lesions should be excised with clear
margins to maximize success.
Consider excising additional tissue to
incorporate a complete facial unit if more than
one third is involved. This produces a more
cosmetic and symmetric repair.
If confronted with indistinct deep margins or a
high probability of recurrence, consider skin
grafting and observation for 6 to 12 months.
Planned reconstruction should never limit
oncologic resection.
If possible, place incisions in a facial
crease, hair-bearing areas, junctions of facial
units, and parallel to relaxed skin tension
lines.
Always plan reconstruction from simple to more
complex microvascular patterns: primary closure
skin graft > local flap > regional flap > free
flap.
If using a local facial flap, consider the
donor site defect and its effect on functional
structures (e.g., eyelid, mouth).
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Laryngoscope 1983;93:87.
22. Swanson NA. Basal cell carcinoma: treatment modalities and
recommendations. Prim Care 1983;10:443.
23. Crissey JT. Curettage and electrodesiccation as a method of
treatment for epitheliomas of the skin. J Surg Oncol 1971;3:287.
24. Zacarian SA. Cryosurgery of malignant tumors of the skin.
In: Epstein E, Epstein E, eds. Skin surgery. Philadelphia: W.B.
Saunders, 1987.
25. Carruth JAS, McKenzie AL. Preliminary report of a pilot
study of photoradiation therapy for the treatment of superficial
malignancies of the skin, head and neck. Eur J Surg Oncol
1985;11:4750.
26. Greenway HT, Cornell RC, Tanner DJ, et al. Treatment of BCC
with intralesional interferon. J Am Acad Dermatol 1986;15:437
443.
27. Uede K, Shimakage J, Ohta C, et al. Skin carcinoma
successfully treated by interferon (IFN) local injection. In:
Abstracts of the Seventeenth World Congress of Dermatology,
Berlin, 1987;1:358.
28. Swanson NA, Grekin RC, Baker SR. Mohs surgery: techniques,
indications, and applications in head and neck surgery. Head Neck
Surg 1983;6:683.
29. Mohs FE. Chemosurgery: a microscopically uncontrolled
method of cancer excision. Arch Surg 1941;42:279.
30. Mohs FE. Microcontrolled surgery for skin cancer. In:
Epstein E, Epstein E, eds. Skin surgery. Philadelphia: W.B.
Saunders, 1987.
31. Tromovitch TA, Stegman SJ. Microscopically controlled
excision of skin tumors. Chemosurgery (Mohs): fresh tissue
technique. Arch Dermatol 1974;110:231.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

104 MALIGNANT MELANOMA
Head & Neck SurgeryOtolaryngology
104




MALIGNANT MELANOMA
JEFFREY N. MYERS
ANDREW J. NEMECHEK

J.N. Myers: Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center,
Houston, Texas.
A.J. Nemechek: Department of OtolaryngologyHead and Neck Surgery, Tulane University School of
Medicine, New Orleans, Louisiana.


Epidemiology
Clinical Presentation and Diagnosis
Mucosal Melanoma
Desmoplastic Melanoma
Staging
Regional Nodal Staging
Imaging and Occult Nodal Disease
Elective Lymph Node Dissection
Sentinel Lymph Node Identification and Biopsy
Treatment
Regional Lymphadenectomy
Therapeutic Neck Dissection and Parotidectomy
Radiotherapy
Systemic Therapy
Interferon
Tumor Vaccination
Systemic Therapy for Metastatic Disease
Surveillance
Conclusion
Chapter References
Increased public awareness and early detection has improved 5-year survival in patients
with cutaneous malignant melanoma (CMM), yet the incidence of CMM has increased at
such an alarming rate that these advances have not translated into lower overall mortality
rates. Traditional staging methods have relied heavily on the tumor depth of invasion and
size of regional nodes. More recent data on clinicopathologic predictors of treatment
outcomes have resulted in a newly proposed staging system that incorporates tumor
ulceration and depth, the presence of satellitosis and in transit metastases, and the number
rather than the size of involved lymph nodes. Furthermore, results from studies of the
regional staging method, sentinel lymph node identification and biopsy, have shown the
sentinel node status to be the most reliable predictor of treatment outcomes. Surgery and
adjuvant postoperative radiation therapy (when indicated) have been shown to be
extremely effective in achieving local-regional control above the clavicles, but distant
failure remains a serious problem. Systemic adjuvant therapy with high dose interferon-
has been shown to improve disease-free survival, although it has not been shown to
significantly impact overall survival. Promising studies of immunotherapy, che-
motherapy, or biochemotherapy for advanced stage disease are accumulating but, again,
have not been proven to increase survival.
We review these recent developments in the staging, evaluation, and treatment of CMM
and their relevance to the management of CMM of the head and neck region. Mucosal
melanomas of the head and neck are also discussed.
EPIDEMIOLOGY
Worldwide, the incidence of melanoma has increased over the past 30 years and
continues to do so at an alarming rate. The number of new cases is increasing
approximately 5% annually (1). By the year 2000, 1 in 75 people in the United States
may develop malignant melanoma during their lifetime. Melanoma is the leading cause
of death from malignancies of the skin, because it accounts for 2% of all cancer deaths in
the United States. People who are fair in complexion and/or who have the tendency to
sunburn easily have an increased relative risk of developing malignant melanoma. Head
and neck melanomas occur more commonly in men (2:1), with a median age of diagnosis
at 55 years with a range of 12 to 92 years (2). Epidemiologic studies demonstrate higher
rates of melanoma in those living in geographic areas that are exposed to intense sunlight
(i.e., Australia). This finding and investigations in the laboratory demonstrate that
exposure to ultraviolet light plays a major role in the pathogenesis of melanoma. This is
further supported by the lower rates of melanoma reported in people whose skin has
natively more pigmentation. One study showed that the incidence of melanoma is
approximately 10 times higher in whites than in blacks in the same geographic region (3).
Although the head and neck accounts for only 9% of body surface area, as many as 15%
to 30% of all melanomas arise within the head and neck.
CLINICAL PRESENTATION AND DIAGNOSIS
The classic hallmark finding that raises suspicion for malignant melanoma is the presence
of a pigmented lesion that changes over a time period of weeks to months. Therefore,
lesions that change substantially in size or color over time should prompt medical
attention. Other features of pigmented lesions, which should alert one to the possibility of
a malignant process, include increases in diameter or height, variations in border, color,
ulceration, itching, pain, and bleeding. Melanomas may also show signs of regression
with involution of a primary lesion, which is often manifested by a halo lesion with a
central area of decreased pigmentation. However, the clinical diagnosis of this disease
may not always be straightforward; not all mela-nomas are pigmented. As many as 10%
of melanomas may lack melanin, some may resemble other cutaneous lesions such as
basal cell carcinoma, and some tumors may not have a surface component. Another
variation in presentation occurs when melanoma has metastasized to the cervical lymph
nodes and no primary lesion can be found.
Once there is a suspicion of melanoma, relevant historic factors associated with increased
risk of developing this disease should be ascertained. These factors include a history of
childhood sun exposure with episodes of severe sun burning and a family history of
cutaneous malignancies, including melanomas. Other types of pigmented lesions are
important to note as well. These include junctional or acquired nevi that are found in the
skin of most adults and are generally less than 5 mm. Dysplastic nevi tend to be larger
and have irregular borders with variation in color. The identification of a dysplastic nevus
should prompt dermatologic evaluation because of an increased risk of developing a
malignant melanoma within these lesions.
Melanoma has been divided into four distinct clinicopathologic subtypes: lentigo maligna
(LM), superficial spreading, and nodular and acral lentiginous melanoma. These lesions
demonstrate either a radial (intraepithelial) or vertical (intradermal) growth phase or a
combination of the two. Radial growth is circumferential in nature and confined to the
dermal-epidermal junction. The vertical growth phase (intradermal) demonstrates
invasion through the dermal-epidermal junction. It is suggested that the radial growth
phase may indicate a lesion's capacity for growth and invasion into the papillary dermis
but may lack metastatic potential (4). Conversely, cells in the vertical growth phase may
represent a clonal change in cells with a growth advantage over neighboring cells,
resulting in the clone's ability to invade and metastasize.
Differential diagnosis of cutaneous melanomas includes seborrheic keratosis, benign nevi
(including junctional, compound, and dermal), hemangioma, blue nevi, pyogenic
granuloma, and pigmented basal cell carcinoma. LM, also known as melanoma in situ, is
a premalignant pigmented lesion that frequently develops in the head and neck region of
elderly patients. Known historically as Hutchinson melanotic freckle, these lesions are
associated with solar skin damage and feature atypical melanocytes, which spread
radially along the dermal-epidermal junction, exhibit focal nesting, and occasionally
extend along skin appendages into the dermis.
Up to 5% of LM or melanoma in situ progress to LM melanoma. LM lesions should be
excised with 0.5-cm margins, though prediction of tumor margins can prove difficult.
When LM lesions become invasive, they are known as LM melanoma. This is the least
common type of cutaneous melanoma and accounts for between 6% and 10% of
melanoma lesions. Its growth is characterized by a slow radial phase that may take up to
10 years to progress. At first, they are quite slow to deeply invade, and affected patients
have a better prognosis when compared with other forms of melanoma.
Superficial spreading melanoma represents the most common type of melanoma and
comprises between 65% and 75% of cases. These lesions may demonstrate a wide variety
of colors, including pink, blue-gray, brown, tan, and black. They may also demonstrate
radial growth for 5 to 7 years and then become invasive, an event frequently heralded by
ulceration and bleeding. High cure rates have been reported when these lesions are
clinically detected in the radial growth phase. Spontaneous regression of superficial
spreading melanomas has also been reported.
Acral lentiginous is the most common type of melanoma seen in the African-American
population. Because these lesions commonly occur on the soles of the feet, surfaces of
the hand, and oral/anogenital mucosa, they are less commonly encountered by head and
neck surgeons. Nodular melanoma comprises between 10% and 15% of all melanomas
and may affect areas of both exposed and non-sun exposed areas of the skin. They tend to
develop in patients older than 50 years. Nodular melanoma is considered to be the most
invasive of the cutaneous melanomas, and affected patients have the poorest prognosis.
When a patient's skin lesion is suggestive of malignant melanoma both by history and
physical examination, biopsy is performed. The technique for obtaining tissue for
pathologic analysis has been the subject of considerable debate. A properly performed
biopsy not only establishes a diagnosis but also provides critical prognostic data and
assists in formulating a specific treatment plan. The type of biopsy is dictated by factors
such as the size of the lesion and its anatomic location in reference to other vital
structures in the head, face, and neck. Furthermore, the site of origin of a primary
melanoma in the head and neck can also be of prognostic significance itself, because
lesions of the scalp and neck are associated with a worse prognosis than melanomas of
the face. Excisional biopsies are the favored technique to obtain tissue for diagnosis, and
several studies have demonstrated an association between decreased survival and
incisional or manipulative biopsies (5). Excision is performed with a narrow margin of
normal-appearing tissue and should include subcutaneous fat for complete evaluation of
the depth.
After excision, the specimen is oriented and discussed with the pathologist. If the lesion's
size or other anatomic constraints preclude excision, the incisional and punch biopsy
techniques are acceptable alternatives. Both should sample the most representative
portion of the lesion. Punch biopsy may include sampling the most raised area of the
lesion or an area with the most pigmentation. Lesions with variable heights, colors, and
borders may require multiple areas to be biopsied for accurate and proper diagnosis.
Finally, fine-needle aspiration, curettage, and shave techniques have no role in evaluation
of suspected invasive melanoma because they may be inadequate in providing precise
information regarding the depth of invasion. It should also be clearly stated that the initial
excisional biopsy with negative margins is not considered adequate therapy for invasive
melanoma.
MUCOSAL MELANOMA
Noncutaneous mucosal melanomas are relatively rare lesions, representing only 2% of all
head and neck melanomas. Greater than 50% of reported cases arise within the nasal
cavity. Other effected areas include the paranasal sinuses, nasopharynx, oral cavity, and
oropharynx (6). Esophageal mucosa may also be affected. Nasal obstruction is the most
common presenting symptom for sinonasal lesions. However, a significant number of
mucosal melanomas may be asymptomatic until they have progressed to an advanced
stage, which contributes to the poor prognosis of patients with this diagnosis. In addition,
Stern (6) found an average of 9 months between the first onset of symptoms and
physician intervention. The differential diagnosis includes vascular lesions, angiomas,
and dental amalgam tattoos. Biopsy is confirmatory. Immunohistochemistry can be
helpful because mucosal melanomas demonstrate similar staining characteristics to their
cutaneous counterparts. It is not uncommon for the characteristic melanosis to be absent
in mucosal melanoma lesions. Ascertaining the depth of invasion is not necessary in
mucosal melanomas because it has little or no prognostic impact for these tumors.
Wide excision of mucosal melanoma is the mainstay of therapy. Radiotherapy in the
adjuvant setting is also suggested, but its benefits have not been proven. Patients may
experience multiple local recurrences and may ultimately succumb to a combination of
uncontrolled local and distant disease. Patients with nasal lesions exhibit improved
survival when compared with those with lesions in the oral cavity, and 5-year overall
survival rates range between 10% and 45%. The development of distant metastasis is an
ominous sign. Stern and colleagues (6) at the MD Anderson Cancer Center found that
most patients that develop distant metastases also have local recurrence and succumb to
their disease.
DESMOPLASTIC MELANOMA
Desmoplastic melanoma is a histologic variant of melanoma that accounts for fewer than
1% of melanoma cases overall. However, as many as 75% of these tumors occur in the
head and neck region. Clinically, desmoplastic melanomas may be amelanotic, a feature
that impedes early recognition and leads to significant delays in diagnosis and treatment.
Another important characteristic feature of these lesions is their neurotropism, which
predisposes them to perineural invasion and spread that often accounts for local
recurrence, despite histologically negative margins. Therefore, it is suggested that
wider resection margins be taken around a desmoplastic tumor and that adjuvant radiation
is considered after definitive excision. The rates of regional metastasis are lower than for
conventional melanomas of comparable tumor thickness. Therefore, regional therapy,
such as lymph node dissection, is usually not advocated for stage I or II disease (7). The
role of sentinel lymph node mapping in the management of desmoplastic melanomas has
not yet been determined.
STAGING
The staging of malignant melanoma has evolved over the past half century in efforts to
determine more reliably a patient's prognosis and to identify the most appropriate
treatment schemes. Petersen (8a), Clark, and Breslow made significant contributions to
the microscopic staging of melanoma. Clark (8) described five categories, currently
known as the Clark levels of invasion, that denote the deepest microscopic anatomic level
penetrated by a melanoma. In the Breslow staging system (9), the maximum thickness of
melanomas is used as a prognostic indicator.
More recently, Buzaid et al. (10) performed an extensive analysis of CMM patients,
correlating their clinical outcomes with clinicopathologic criteria. Based on this study,
they proposed a new staging system (10). The American Joint Committee on Cancer has
incorporated many of their recommendations and will include these in their next iteration
of its staging for CMM, which will be presented in 2002 (11). This staging method is
based on evaluation of the primary tumor, regional metastasis (satellites, in-transit, and
lymph node disease), and presence/location of distance metastasis.
Evaluation of the primary tumor is based on the lesion thickness measured from the
granular cell layer to the deepest point of invasion. The importance of ulceration of the
primary lesion is also denoted in the new T classification. In addition, the American Joint
Committee on Cancer noted that discrepancies between tumor thickness and Clark level
are settled in favor of the least favorable T stage. Approximately 75% of patients with
melanoma of the head and neck present with intermediate thickness lesions (0.75 to 4.0
mm). Although cutoff points for T stage have traditionally been 0.75, 1.50, and 4.0 mm,
Buzaid et al. and others (12) found that T stages based on depths of invasion of 1.0, 2.0,
and 4.0 mm are easier to use and more accurate.
REGIONAL NODAL STAGING
Evaluation for regional metastasis relies on both physical examination and
complementary imaging studies. In the head and neck, lateralized tumors may drain into
the primary echelon nodal basins, including preauricular, parotid, posterior cervical,
anterior cervical (internal jugular), and supraclavicular nodal groups. Nodal drainage
basins in the head and neck are less predictable when compared with truncal and
extremity sites. Although some areas on the scalp, face, and ears may have predictable
lymphatic drainage, bilateral or contralateral metastases are not uncommon, and
ambiguous drainage patterns can be seen in up to 55% of patients. Posterior scalp lesions
may have lymphatic drainage to occipital basins as well. Recent studies using
preoperative and intraoperative lymphoscintigraphic methods have helped to further
define the patterns of lymphatic drainage in primary melanomas of the head and neck
region (13,14).
The risk of regional metastasis varies directly with tumor thickness. Those measuring less
than 0.75 mm demonstrate virtually no risk. Those measuring between 0.76 and 1.49 mm
have a 25% risk of regional metastasis. Lesions 1.5 to 3.9 mm in greatest thickness have
up to a 60% of risk of regional metastasis. Those measuring greater than 4 mm in
thickness have greater than 65% incidence of regional metastasis. When physical
examination reveals palpable lymphadenopathy, computed tomography (CT) or magnetic
resonance imaging (MRI) is often used to determine the number and extent of cervical
metastases.
The recent study by Buzaid et al. (15) showed that the number of lymph nodes involved
with regional metastases is more predictive of treatment outcomes than is the size of
lymph nodes harboring metastatic disease. Furthermore, complete staging for distant
metastases is critical in patients with melanoma. Therefore, serologic studies, including
liver function tests, and CT of the brain, chest, and abdomen are recommended.
Lymphoscintigraphy may provide an adjunctive method of defining the pathways of
regional metastasis. It may be particularly helpful when the primary tumor is located in
the midline (scalp, forehead) and has potential bilateral drainage, including one or both
parotid glands. As stated, the most important factor in survival in patients with head and
neck melanoma is the presence or absence of lymph node metastasis. When palpable
lymphadenopathy is present, fine-needle aspiration biopsy can often be used to confirm
the metastasis. Once the presence of lymph node involvement by tumor is confirmed, a
therapeutic lymph node dissection is recommended.
Imaging and Occult Nodal Disease
The evaluation and treatment for occult regional metastasis is perhaps the most
controversial aspect of the management of CMM of the head and neck (16). Patients with
lesions of less than 1 mm in depth and Clark level less than IV who do not have palpable
lymphadenopathy are most often observed. For those patients having lesions more than 1
mm in depth or Clark level IV or V, there are several options to determine the pathologic
nodal status.
The rationale for the determination of nodal status is to identify patients who would
benefit from regional therapy with either surgery or radiation therapy to effect local
regional control and to identify patients at greater risk for systemic recurrence who could
potentially benefit from systemic adjuvant therapy. Although traditional imaging methods
such as ultrasound, CT, and MRI may slightly increase the sensitivity in detecting
regional metastases over palpation alone, they are still not completely reliable in
distinguishing regional metastatic disease from reactive adenopathy. Early reports of the
use of metabolic nuclear medicine imaging methods, such as single photon emission CT
and positron emission tomography, suggest that these may eventually be useful methods
for identifying occult disease.
Elective Lymph Node Dissection
Another technique to identify occult regional metastatic disease is elective lymph node
dissection (ELND) (16). The use of ELND in the management of patients with CMM of
intermediate thickness or thicker lesions has been frequently debated. This debate was
largely put to rest by a prospective, multiinstitutional, randomized trial led by The
Intergroup Melanoma Surgical Trial that compared ELND to observation for stage I and
II melanomas from all regions of the body (17). This study found no survival benefit to
ELND except in patients under 60 years of age or those who had lesions 1 to 2 mm in
depth. Whether ELND can help improve survival by identifying those with occult disease
who might benefit from systemic adjuvant trials has not been resolved. However, the
development of sentinel lymph node biopsy (SLNB) may enhance the sensitivity and
specificity of ELND or could replace it in the assessment of regional metastatic disease in
patients with CMM of the head and neck region (18).
Sentinel Lymph Node Identification and Biopsy
For patients with CMM below the clavicles, sentinel lymph node mapping and biopsy has
been the greatest single advance in the evaluation and treatment of patients (18).
Although there have been some studies of this novel methodology in CMM of the head
and neck region, its ultimate role in head and neck surgical oncology remains to be
determined by further investigation (19).
The SLNB concept was first introduced by Donald Morton, who hypothesized that within
each nodal basin, there is an orderly progression of lymphatic drainage from a first
echelon or sentinel node to nodes of lower echelons (18). A natural corollary is that if one
can identify the sentinel lymph node in a basin at risk for spread from a melanoma and
find it to be free of metastasis, then the remainder of nodes in that basin should also be
free of metastatic tumor (20). This concept has been subsequently supported in a number
of trials for non-head and neck CMM, and this has led to the wide practice of this
technique as a staging method to determine whether further regional or systemic therapy
may be beneficial.
Numerous techniques for intraoperative localization and mapping have been described.
These usually include intraoperative identification of sentinel lymph nodes by their blue
color after preexcisional injection of the primary site with isosulfan blue dye and/or use
of a hand-held gamma probe to find nodes that take up a radioactive colloid tracer.
Gershenwald et al. (21) reported the results of a multiinstitutional study using lymphatic
mapping for stage I and II melanoma patients. In this study the status of the sentinel
nodes was found to be the strongest predictor of disease-free survival. Further, the study
concluded that nodal status helps to stratify patients for whom adjuvant therapy is not
indicated.
An additional benefit of SLNB is that it can focus a more extensive evaluation of lymph
nodes at risk for subclinical metastases. The work of Gershenwald et al. (22) at the MD
Anderson Cancer Center has shown that serial sections of a sentinel lymph node can
increase the sensitivity in detection of nodal metastases, thereby improving the selection
of patients who receive regional and systemic treatment. The use of frozen sections for
evaluation of a sentinel lymph node is controversial because false negatives have been
reported. Additional studies that can be used to evaluate the sentinel node include HMB-
45 and S-100 for immunohistochemical analysis and reverse transcription polymerase
chain reaction (23).
Despite its promise, the role of SLNB has yet to be fully defined in the management of
CMM of the head and neck region. The complexity of lymphatic drainage patterns and
the frequent need to remove sentinel lymph nodes from the parotid gland, placing the
facial nerve at risk, have made head and neck surgical oncologists slow to adapt this
method. Wells and colleagues (23a) at the University of South Florida reviewed their
experience with lymphatic mapping using preoperative lymphoscintigraphy and
intraoperative blue dye localization and a hand-held gamma probe in 58 consecutive
patients with head and neck melanoma. The authors successfully identified the sentinel
nodes in 95% of patients, and six patients (10.3%) were found to have histologically
positive sentinel nodes. Five patients went on to have parotidectomy, neck dissection, or
both. None of the patients in the series with negative sentinel nodes had disease in higher
level nodes. In the patients who had positive sentinel nodes, 6 of 18 sentinel nodes were
positive versus 0 of 139 other lymph nodes examined. The low false-negative rate of
lymphatic mapping reported in this study lends further support for the use of this method
for staging the regional lymphatics in patients with melanoma of the head and neck.
Alex and colleagues (23b) recently reported on their experience with lymphatic mapping
in 23 clinically node-negative patients with intermediate-thickness melanoma using vital
blue dye mapping and a hand-held gamma probe. These authors successfully resected the
sentinel lymph node in 96% of patients. Three patients (13%) had sentinel nodes positive
for melanoma, and only one patient with negative sentinel nodes (5%) developed a
regional recurrence.
The data from these studies suggest that lymphatic mapping using the combination of
blue dye and a hand-held gamma probe is an effective method for ruling out regional
metastases in patients with melanoma and may be a particularly good method for
identifying patients who might benefit from systemic adjuvant therapy. However, there
are several arguments against the use of lymphatic mapping for melanoma in the head
and neck region.
O'Brien et al. (14) at the Sydney Melanoma Unit pointed out some limitations of
lymphatic mapping in the treatment of head and neck melanoma in a study of 97 patients
who underwent lymphoscintigraphy. These authors found a high rate (34%) of
disagreement between clinically predicted lymphatic drainage pathways in the head and
neck region and the pathways found on the basis of lymphoscintigraphy. Their analysis
also revealed a large number of sentinel lymph nodes for each patientonly 13 patients
had a single sentinel node. Thirty-three patients had two sentinel nodes, 3 had three
sentinel nodes, 15 had four sentinel nodes, and 6 had five sentinel nodes, indicating the
complexity of lymphatic mapping in the head and neck region. These authors also
reported difficulty in the operative identification of all sentinel lymph nodes found on
lymphoscintigraphy. In addition, the rate of regional failure was 25% among 16 patients
found to have histologically negative sentinel nodes. Furthermore, identification of
sentinel lymph nodes may frequently require extensive dissection in multiple areas of the
neck and parotid gland.
TREATMENT
After thorough preoperative workup that includes staging of the primary and evaluation
for regional and distant metastasis, therapeutic options are discussed with the patient.
Surgical resection has been the mainstay of therapy in the treatment of primary cutaneous
melanoma in the head and neck. Treatment includes resection of the primary melanoma
or previous biopsy site with a rim of normal-appearing tissue surrounding it. The minimal
resection margin necessary for adequate resection has been the topic of debate.
Historically, 5-cm excision margins were suggested based on the propensity of
melanomas to recur in areas adjacent to the primary site, although no survival advantages
could be shown by its proponents (24). Based on subsequent retrospective analyses, it
was suggested that narrower resection margins might be appropriate for thin or
intermediate-thickness lesions (25). Recent randomized trials concluded that local and
regional control rates and survival were not different when excisions with large (5-cm)
margins and those using more conser-vative (2-cm) margins were compared (26,27).
In a collaborative retrospective review, investigators at the University of Texas MD
Anderson Cancer Center and the Moffett Cancer Center found no increase in local
recurrence rates or worse survival rates in patients when thick primary melanomas (more
than 4 mm) were excised with a margin of 10 mm or less (27).
The current recommendations for adequate resection margins include the following (each
dependent on anatomic constraints):
in situ, 0.5 cm
1 to 2 mm, 1.0 cm
2 to 4 mm, 2.0 cm
>4 mm, >2 cm
Frequently, in the head and neck, proximity of structures such as the eyes, nose, ears, and
circumoral anatomy effectively limits the borders for excision. Excisions are carried out
in a full-thickness fashion down to underlying fascia such that all margins, including
those that are deeply invaded, may be effectively evaluated. Significant controversy
exists regarding the use of frozen section for evaluation and diagnosis. However, in later
work, Zitelli et al. (28) reported that frozen sections of analysis for surgical margins of
melanoma had sensitivity and specificity of 100% and 90%, respectively. The use of
frozen sections may be particularly helpful in areas of the head and neck where limited
margins are used because of functional or cosmetic concerns. After resection and control
of margins by frozen section, a reconstruction can be carried out. Methods of
reconstruction after resection for melanoma are beyond the scope of this chapter.
However, most lesions can be enclosed either primarily with the use of local
advancement flaps or with the use of skin grafting techniques.
REGIONAL LYMPHADENECTOMY
Therapeutic Neck Dissection and Parotidectomy
For patients with clinically positive lymph nodes, neck dissection is recommended.
However, the extent of neck dissection remains an area of controversy but ranges from
removal of gross disease by selective lymphadenectomy to radical neck dissection and its
modifications. Studies from Memorial Sloan Kettering Cancer Center and the Melanoma
Unit in Sidney, Australia have investigated the effect of neck dissection on outcome for
patients with melanoma (14). Shah and colleagues (28a) concluded that in the presence of
clinically positive lymph nodes a comprehensive neck dissection should be carried out.
The type of neck dissection was tailored to the site of the primary tumor. For instance, in
patients with melanomas of the face, ear, and anterior scalp, dissection of the parotid
gland and lymph node levels I through IV was carried out. Patients with lesions in the
postauricular and posterior scalp and neck required dissections of levels II through V. A
complete discussion as to type and technique of neck dissection can be found elsewhere
in this text.
RADIOTHERAPY
Like many issues important to the treatment of malignant melanoma, radiotherapy, both
as the primary modality of therapy and in the adjuvant setting, has sparked much
controversy in the past century. Conflicting reports as to its efficacy included
investigators unabashedly stating that malignant melanoma cells were radioresistant.
However, Barranco et al. (29) found by using cultured malignant melanoma cells that
melanoma cells differ from other types of tumor cells in their radiosensitivity. In
addition, they found that the observed radioresistance of melanoma could be overcome
by increasing the individual dose fraction. These studies have helped form the basis for
clinical practice, and subsequent studies helped to determine the ideal fraction size and
total therapeutic dose that effectively treats melanoma.
Generally, radiotherapy is not recommended for the primary treatment of CMM.
However, in some exceptional circumstances its use is advocated. In elderly patients who
are poor candidates for surgical resection, radiotherapy may offer an acceptable
alternative. Also for those patients with extensive facial LM melanoma that precludes
adequate surgical resection based on cosmetic considerations, radiotherapy serves as an
excellent alternative.
Radiotherapy has been shown to be very effective in the postoperative adjuvant setting in
achieving high rates of local-regional control in patients with high-risk CMM of the head
and neck region in a prospective nonrandomized clinical trial carried out at The
University of Texas MD Anderson Cancer (30). This study involved three subgroups of
patients. The first group had primary lesions greater than 1.5 mm or had lesions
extending to Clark level IV or V and received elective radiation after a wide local
resection. The second group presented with palpable lymphadenopathy and received
radiation in the adjunctive setting after excision of primary lesions coupled with a
therapeutic neck dissection (selective or modified radical). The last group of patients
underwent radiation after therapeutic neck dissection for regionally recurrent melanoma.
Radiotherapy was delivered in five fractions of 6 Gy, twice weekly to a total dose of 30
Gy. For 174 patients, only 6 patients developed recurrence above the clavicles, whereas
58 patients developed distant metastases. The 5-year survival rate was 47%, and the
local-regional control rate was 88% for all patients. The 5-year survival rate of the first
group of patients was strongly influenced by thickness of the primary lesion. Patients in
groups 2 and 3 with less than three involved lymph nodes at the time of neck dissection
had significantly higher survival rates than those with three or more involved lymph
nodes. In summary, patients should be considered for radiotherapy either to the primary
site and/or regional nodal basins whose primary lesions measure 1.5 mm or greater or are
ulcerated. Also, patients who present with regional metastasis should be offered
radiotherapy after excision of primary tumor and neck dissection. Additionally, patients
with primary melanomas that demonstrate neurotropism (desmoplastic type) should be
considered for radiotherapy after excision. Controversy remains regarding the use of
lymphatic mapping and SLNB in an effort to guide the use of regional radiotherapy in
absence of a formal neck dissection.
SYSTEMIC THERAPY
There are two major indications for systemic therapy in management of patients with
CMM. The first indication is the adjuvant treatment of patients who have completed
local-regional therapy and have no evidence of local, regional, or systemic disease but
who are thought to be at high risk for systemic relapse. The second indication for
systemic treatment is the presence of distant metastases. There are a number of systemic
therapy options available to treat patients with either of these indications, including
single-agent or multiple-agent chemotherapy, biochemotherapy, or strategies using
immune modulation.
A number of clinical studies have been designed to evaluate the role of systemic adjuvant
therapies for patients who have completed local regional treatment and who are believed
to be at high risk for the development of distant metastatic disease. Although no universal
definition exists for the high-risk patient, a number of studies have accrued patients with
primary lesions that are ulcerated lesions, more than 4 mm in depth or Clark level IV, or
those patients with satellitosis, in transit disease, or nodal metastases.
Interferon
Interferon- is one of the most well-studied agents for the systemic adjuvant therapy of
CMM arising from all sites (31,32). However, it has yet to be shown unequivocally to
improve overall survival for these patients. The interferons are a family of proteins that
have both immunostimulatory and antiangiogenic activity and have excellent preclinical
antitumor activity in a number of systems. A prospective, randomized, clinical trial of
high-dose interferon- in the treatment of patients with high-risk melanoma was
conducted by the Eastern Cooperative Oncology Group (31). High-risk patients were
given high-dose interferon alfa-2b, 20 MU/m
2
a day intravenously for 4 weeks. This was
followed by 10 MU/m
2
a day administered subcutaneously 2 days weekly for the
remainder of the year. Increases of prolonged survival of 2.8 to 3.8 years were observed,
and the recurrence-free survival ranged from 1 month to 1.7 years. The survival
advantages were statistically significant in patients with regional lymph node metastasis.
Most patients experienced significant toxicity that included chills, fevers, myalgias, and
other constitutional symptoms including fatigue and anorexia. A follow-up trial of high-
and low-dose interferon alfa-2b in high-risk melanoma, E1690, was recently reported by
the Intergroup (32). This study did not confirm the earlier improvement in overall
survival but did demonstrate a dose-dependent improvement in 5-year recurrence-free
survival rates from 35% to 44%.
Tumor Vaccination
Vaccination is another widely studied strategy for systemic adjuvant therapy of the high-
risk melanoma patient, and a variety of different immunization approaches has been used.
These studies are predicated on several clinical observations and lines of basic
investigation that indicate that the immune system can eradicate melanoma cells and that
immune stimulation can overcome immune tolerance to tumor antigens to enhance the
immune surveillance of tumor cells. Although a comprehensive review of available
vaccine strategies is beyond the scope of this review, some of the more encouraging
studies are discussed. Ganglioside GM2, an antigen overexpressed by many melanoma
cells, given in combination with BCG or other immune adjuvants was developed by Dr.
Alan Haughton and colleagues at Memorial Sloan Kettering Cancer Center and has had
promising results in clinical trials (33). Currently, there is an ongoing intergroup study
with ECOG, SWOG, and the MD Anderson Cancer Center in which patients are
randomized to receive either high-dose interferon- or conjugate GM2 vaccination.
Dr. Donald Morton and colleagues at the John Wayne Cancer Center have developed a
polyvalent melanoma cell vaccine capable of inducing humoral and cell-mediated
immune responses to melanoma-specific antigens. This is currently undergoing
evaluation in a phase III randomized study. Other cancer vaccines have been identified by
Dr. Steven Rosenberg and co-investigators at the surgery branch of the National Cancer
Institute using specific peptide antigens recognized by autologous tumor-specific T-cell
clone reactivity. These peptide vaccines are most often administered with cytokine or
cellular immune adjuvants, such as dendritic cells. It is difficult to advocate any of the
current vaccine strategies over another. Therefore, we recommend that patients with
high-risk melanoma are enrolled into prospective trials to test these adjuvant therapeutic
strategies.
Another approach to adjuvant therapy is currently being evaluated by the Melanoma
Medical Oncology Service at the University of Texas MD Anderson Cancer Center, and
this approach includes the use of biochemotherapy in which conventional
chemotherapeutic drugs are combined with the biologically active agents interferon-
and interleukin-2 (IL-2). Currently, biochemotherapy is being compared with high-dose
interferon- alone in a prospective randomized trial at that institution (34).
Systemic Therapy for Metastatic Disease
The prognosis of patients with metastatic melanoma is poor; those with liver, brain, or
bone metastasis have a median survival of only 3 to 4 months. Chemotherapy using
single-agent dacarbazine (DTIC) or combinations such as BCNU, cisplatin, lomustine,
and hydroxyurea has been reported. The trials comparing DTIC alone or in combination
with other agents have shown a significant though brief improvement in survival. The
combination of DTIC with cisplatin and vinblastine, CVD, has been given along with
interferon- and IL-2 either simultaneously or sequentially as biochemotherapy for
patients with metastatic melanoma (34,35). In 114 patients with stage IV disease who
received either sequential or concurrent bichemotherapy, a complete response rate of
21% and a partial response rate of 39% have been obtained with a prolongation in
survival over CVD alone from 9 to 13 months (35).
Based on the immunoresponsiveness of melanoma, Atkins and colleagues treated several
hundred patients with metastatic melanoma with high-dose bolus recombinant IL-2 since
September 1985 and found a complete response rate of 7% with 10% partial responses
(36). Of the 10 patients who had complete responses, 8 had durable responses. The
determinants of response to this toxic form of treatment have not been identified at this
point, which have made widespread application of this form of treatment impractical.
Current studies are focused on the use of IL-2 given with melanoma peptide antigens or
melanoma-specific in vitro expanded autologous tumor-infiltrating lymphocytes.
Outcomes of this promising work are much anticipated.
SURVEILLANCE
With a rapidly increasing rate of melanoma worldwide, the importance of surveillance of
even benign-appearing lesions is understood. The importance of dermatologic evaluation,
photo documentation, and close follow-up cannot be overstated. In patients with a
diagnosed malignant melanoma, between 55% and 70% of those with recurrences appear
within the first 2 years of therapy and up to 80% of recurrences will be diagnosed in the
first 3 years after treatment (37). Those with regional metastasis at presentation may have
clinically evident tumor recurrences within 24 months. The time to recurrence also
correlates with primary tumor thickness, ulcerations, and increasing patient age. Physical
examination, liver function serology, and chest radiography will detect most of these
recurrences; therefore, routine screening with CT of the head, chest, and abdomen is not
recommended. The National Cancer Institute has reported a consensus statement on the
follow-up evaluation of patients with early melanoma. Most patients without a family
history and no atypical nevi should have follow-up evaluations every 6 months for the
first 2 years. Thereafter, yearly follow-up is appropriate. Those with a family histories or
atypical nevi are followed every 3 months. The guidelines in Table 104.1 have been
recommended for the surveillance of patients who have no evidence of disease after
treatment for CMM.

TABLE 104.1. RECOMMENDED GUIDELINES
FOR THE SURVEILLANCE OF PATIENTS WHO
HAVE NO EVIDENCE OF DISEASE AFTER
TREATMENT FOR CMM



CONCLUSION
The incidence and mortality rate of CMM are rapidly increasing worldwide. Features of
the history and physical examination that are suggestive of malignant melanoma include
changes in size or color, sensation of the lesion, and variations in color and margin
surface. The presence of ulceration is also quite important. When a suspicious lesion is
encountered, excisional biopsy is performed that includes subcutaneous fat for complete
evaluation of lesion depth. Biopsies that do not evaluate depth, such as fine-needle
aspiration and curettage, have no role in evaluation in suspected melanoma. Once
invasive melanoma is diagnosed, histologic type is assessed and lesion thickness is
established. Tumor thickness (Breslow) and level of invasion (Clark) are prognostically
important. Staging in relation to the presence of regional and distant metastasis is
established by physical exam, liver function serology, and chest radiograph in stage I and
II disease. Additionally, imaging of the head, chest, and abdomen is recommended for
patients with stage III and IV disease.
Lymphoscintigraphy may provide an adjunctive method of identifying sentinel lymph
nodes and defining routes of lymphatic spread, especially in patients with primary tumors
located in the midline that have predicted drainage basins that are ambiguous or include
both parotid glands. After staging, a treatment strategy is formulated. For melanomas less
than 1 mm in thickness and no evidence of regional metastasis, surgical excision is
carried out with close surveillance thereafter. Current recommendations for adequate
resection margins, dependent on anatomic constraints, range from 0.5 to greater than 2
cm depending on the thickness of the primary lesion. For patients with lesions greater 1
mm thick and for ulcerated lesions without regional metastasis, excision is offered along
with a procedure to assess the status of the regional lymph node, such as SLNB
performed in the context of an ELND. Once SLNB is performed, serial sectioning of the
lymph node(s) is carried out to increase the sensitivity of pathologic identification of
metastases.
In patients with regional lymph nodes that are found to be pathologically positive,
radiotherapy is offered. Dosages of 6 Gy are delivered twice weekly over 2.5 weeks to a
total of 30 Gy. In addition, patients with ulcerated lesions or those with lesions greater
than 1.5 mm or with Clark's level IV who do not undergo ELND or SLNB are
recommended to receive adjuvant radiotherapy. Patients who present with clinically
positive lymph nodes should undergo excision of the primary lesion and a therapeutic
neck dissection that may be modified to preserve neurovascular structures. Parotidectomy
is performed if parotid lymph nodes are included in nodal drainage basins. These patients
should also be evaluated for systemic adjuvant therapy, as should those who present with
or develop distant metastasis. The use of systemic therapy includes chemotherapy,
bioimmunotherapy, and vaccination, all of which can be used to treat metastatic disease
or in the adjuvant setting for patients without evidence of disease who are at high risk for
systemic failure.
Although the number of patients affected with melanoma is increasing, survival rates are
improving due to early detection programs and heightened awareness on the part of the
general population. It is hoped that this heightened awareness, coupled with progress
made in improved pathologic description and staging and the use of systemic therapies
including immune modulation, will result in continued improvement in our ability to cure
patients with this disease.

HIGHLIGHTS
Increased public awareness and early detection has improved
survival in patients with CMM, yet the incidence of CMM
worldwide is increasing at an alarming rate.
A skin lesion that changes in size, color, and sensation or one
that ulcerates or bleeds requires prompt medical attention.
Histologic evaluation is carried out via biopsy techniques (i.e.,
excisional) that include subcutaneous fat for complete
evaluation of depth. Fine-needle aspiration and curettage have
no role in the evaluation of suspected melanoma.
Local disease staging involves evaluation of thickness
(Breslow) and invasion level (Clark) and the presence or
absence of tumor ulceration. In the staging of regional disease,
the presence of satellite lesions, in transit disease, and the
number (rather than the size of) involved lymph nodes are all of
prognostic significance. The type of distant metastasis is also
significant.
For patients with primary tumors without evidence of regional
or distant spread on physical examination (stages I and II),
chest x-ray and liver function tests comprise the recommended
workup. For patients with regional and/or systemic metastases,
a comprehensive staging workup should include brain MRI and
CT of the chest, abdomen, and pelvis. Ultrasound, CT, or MRI
of the neck is also often included for regional staging in patients
with either early- or late-stage disease. Lymphoscintigraphy
and sentinel node mapping may provide and additional means
of identifying regional disease for tumors located in areas with
ambiguous predicted drainage patterns or that include both
parotid glands.
Nonulcerated melanomas less than 1 mm in thickness without
regional metastasis are excised with adequate margins, dictated
by anatomic constraints.
Melanomas more than 1 mm or ulcerated lesions without
regional metastasis are excised, and consideration is given to
lymphoscintigraphy and SLNB with ELND, followed by
pathologic evaluation by serial sectioning.
Patients with regional metastasis should undergo neck
dissection and should be considered for adjuvant
hypofractionated radiotherapy, given to a total dose of 30 Gy.
Patients with high-risk primary tumors and/or regional
metastasis should be evaluated for systemic adjuvant therapies,
including chemotherapy, bioimmunotherapy, and vaccination
given in the context of approved prospective clinical trials.
Patients with distant metastases should be considered for trials
of systemic therapies such as chemotherapy, biochemotherapy,
or immunotherapy.
Vigilant follow-up is mandatory, and recommended intervals
relate to the patient's original staging characteristics.
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14. O'Brien CJ, et al. Prediction of potential metastatic sites in cutaneous head and neck melanomas
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15. Buzaid AC, et al. Prognostic value of size of lymph node metastases in patients with cutaneous
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20. Reintgen DS, et al. An orderly progression of melanoma nodal metastases. Ann Surg
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21. Gershenwald J, et al. Multi-institutional melanoma lymphatic mapping experience: the prognostic
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institutional randomized surgical trial. Ann Surg Oncol 1996;3:446.
27. Heaton K, et al. Surgical margins and prognostic factors in thick (>4 mm) primary melanoma
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28. Zitelli JA, Moy RL, Abel E. The reliability of frozen sections in the evaluation of surgical margins
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Shah JP, et al. Patterns of regional lymph node metastases from cutaneous melanomas of the head and
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

105 NEOPLASMS OF THE NOSE AND PARANASAL SINUSES
Head & Neck SurgeryOtolaryngology
105




NEOPLASMS OF THE NOSE AND PARANASAL
SINUSES
RICARDO L. CARRAU
EUGENE N. MYERS

R.L. Carrau and E.N. Myers: Department of Otolaryngology, University of Pittsburgh School of
Medicine, Eye and Ear Institute, Pittsburgh, Pennsylvania.


Epidemiology
Evaluation
Diagnosis
Pathology
Staging
Principles of Treatment
Surgery
Radiation Therapy
Chemotherapy
Treatment by Site of Origin
Management of Advanced Tumors
Orbital Invasion
Cervical Metastasis
Pterygopalatine Fossa
Infratemporal Fossa and Skull Base
Complications
Orbital
Skull Base Complications
Emergencies Associated With Sinonasal Tumors
Bleeding
Vision Impairment
Infection
Cerebrospinal Fluid Leak or Pneumocephalus
Chapter References
EPIDEMIOLOGY
Malignant tumors of the sinonasal tract constitute less than 1% of all malignancies and
about 3% of those arising in the upper respiratory tract. They occur most commonly in
whites, and the incidence in males is twice the incidence in females (1,2,3,4,5 and 6).
Exposure to industrial fumes, wood dust, nickel-refining processes, and leather tanning
have been implicated in the carcinogenesis of certain types of sinonasal malignant
tumors. Other industrial exposures associated with an increased incidence of sinonasal
cancer include mineral oils, chromium and chromium compounds, isopropyl oils, lacquer
paint, soldering and welding, and radium dial painting. Tobacco smoking does not appear
to be a significant etiologic factor for tumors of the sinonasal tract.
EVALUATION
Diagnosis
Tumors of the sinonasal tract commonly present with symptoms that are identical to
those caused by inflammatory sinus disease, such as nasal airway obstruction, pain,
epistaxis, and nasal discharge. Furthermore, sinonasal tumors are asymptomatic in 9% to
12% of patients, contributing to a delay in the diagnosis (2,5).
Regional and distant metastases are infrequent despite the advanced stage of the primary
tumors. The incidence of cervical metastases on initial presentation varies from 1% to
26%, with most large series reporting less than 10%. The presence of distant metastasis
on initial presentation is even less common, with most series presenting an incidence of
less than 7%.
The physical examination should be thorough, with emphasis on the sinonasal region and
orbit, and should include a nasal endoscopy. Special attention should be given to
evaluating the function of the cranial nerves. Although not pathonogmonic, numbness or
hypesthesia of the infraorbital (V
2
) or supraorbital (V
3
) nerve strongly suggests malignant
invasion. Other findings such as proptosis, chemosis, extraocular muscle impairment,
mass effect in the cheek, gingiva or gingivobuccal sulcus (e.g., ill-fitting dentures), and
loose dentition also suggest the presence of a sinonasal tumor. Table 105.1 provides a
summary of diagnostic techniques.

TABLE 105.1. DIAGNOSIS PARANASAL
TUMORS



Radiologic imaging is essential during the staging evaluation. Plain films demonstrate
bone destruction in 60% to 90% of patients with malignant sinonasal tumors; however, a
significant number will be interpreted as normal (1,2,4). A screening computed
tomography (CT) is more accurate than plain films to evaluate the bony framework of the
paranasal sinuses and compares favorably with the cost of a sinus series.
Patients with a history of exposure to the previously discussed carcinogens; those
presenting with severe persistent pain, cranial neuropathies, exophthalmos, chemosis,
sinonasal disease, and bone erosion on plain films; or those with persistent symptoms
after adequate medical treatment should be evaluated with a high index of suspicion.
Patients in these high-risk groups should be imaged by axial and coronal CT with contrast
or by magnetic resonance imaging (MRI). CT is superior for the evaluation of the bony
confines of the sinonasal tract and skull base. The use of contrast provides an estimate of
the tumor vascularity and its relationship to the carotid artery.
MRI differentiates adjacent tumor from soft tissue, differentiate secretions in an
obstructed sinus from a space-occupying lesion, demonstrates perineural spread, suffers
less artifact effect with dental fillings, offers the advantage of imaging in the sagittal
plane, and does not involve exposure to ionizing radiation. Coronal MRI images allow a
side-to-side comparison and thus are superior for the evaluation of the foramen
rotundum, vidian canal, foramen ovale, and optic canal. Sagittal images are most useful
to demonstrate the replacement of the normal low-intensity signal of Meckel cave and the
high-intensity signal of fat in the pterygopalatine fossa (PtPF) by tumor signals similar to
brain in echo time images. MRI, however, is more expensive than CT and takes longer to
perform, making it more prone to motion artifact, and some patients will not tolerate the
procedure due to claustrophobia.
Angiography with carotid flow study is reserved for surgical candidates presenting with
tumors that surround the carotid artery or when sacrifice of the vessel is anticipated to
obtain clear margins (6). The balloon occlusion test, used with single photon emission
CT, xenon CT, or transcranial Doppler, offers a reasonable estimate of the risk of
ischemic brain infarction if the internal carotid artery is sacrificed. These tests, however,
cannot predict ischemia at marginal (watershed) areas or embolic phenomena.
A CT of the chest and abdomen is recommended for patients presenting with tumors that
metastasize hematogenously, such as sarcomas, melanoma, and adenoid cystic
carcinoma. This extensive workup is important if an extensive resection, such as a
craniofacial procedure, is being considered. A lumbar puncture and brain and spine
imaging are recommended for tumors that invade the meninges or brain and drop
metastasis, a finding that may be associated with meningeal carcinomatosis.
Pathology
The sinonasal tract pathology, with certain important exceptions, reflects the pathology
found in other areas of the head and neck (Table 105.2). We provide a brief description of
the most common histologic diagnoses.

TABLE 105.2. TUMORS OF THE SINONASAL
TRACT



Benign Epithelial Tumors
Papillomas may arise from squamous or schneiderian epithelium. The keratotic papilloma
of the vestibule (vestibular wart) behaves like other cutaneous counterparts. It is easily
treated by simple excision or cauterization. Papillomas of the nasal cavity may be
classified in three distinct categories (Table 105.3) (7). Although benign in nature, they
extend beyond their site of origin, tend to destroy bone, recur when not excised
completely, and may be associated with malignant tumors (7,8 and 9). They are most
commonly diagnosed in white males in the fifth to the seventh decade (mean, 50 years)
(7). En bloc resection has been the gold standard for the treatment of these lesions (Table
105.4). However, MRI, CT, and nasal endoscopy permit an accurate preoperative
mapping of these lesions, allowing more conservative resection. During the last decade,
several authors have reported the use of endoscopic and microscopic transnasal
approaches for the resection of inverting papillomas (9). Transnasal techniques avoid the
use of incisions and usually require a shorter hospital stay than external approaches.
However, even in expert hands, it is associated with a higher recurrence rate than en bloc
resections.

TABLE 105.3. PAPILLOMAS OF THE SINONASAL
TRACT



TABLE 105.4. RECURRENCE RATES FOR
INVERTING PAPILLOMA



Endoscopic techniques can also complement external ap-proaches, especially when the
papilloma extends posteriorly or superiorly beyond the areas comprised by the medial
maxillectomy. The endoscopic approach provides superior visualization of the posterior
ethmoid cells, especially those that extend lateral to the sphenoid sinus or around the
optic nerve (Onodi cells).
Adenomas of the sinonasal tract arise more commonly in the nasal septum, which is
interesting considering the fact that most minor salivary glands are located in the lateral
nasal wall. Most are found during the fourth to the seventh decade, occurring with an
equal sex distribution. The recurrence rate is low after complete removal (10%).
Malignant Epithelial Tumors
Squamous cell carcinoma (SCCA) is the most common tumor of the sinonasal tract
(Table 105.5) (1,2,5,10,11). It is most commonly reported in white males in their fifth to
sixth decade. The prognosis is related to the extent of the tumor and the site of origin.

TABLE 105.5. SQUAMOUS CELL CARCINOMA
OF THE SINONASAL TRACT



Adenocarcinomas make up 4% to 8% of all sinonasal tumors (12). They originate most
commonly at the ethmoid sinuses and nasal cavity. Adenocarcinomas may be divided
into low and high grades according to their histologic characteristics and behavior. Low-
grade tumors present a uniform glandular architecture and cytologic characteristics, with
rare mitoses and seldom perineural invasion or distant metastases. Low-grade
adenocarcinomas tend to recur locally. High-grade adenocarcinoma has a solid growth
pattern with poorly defined margins, prominent pleomorphism, and large number of
mitoses. One third of patients with high-grade adenocarcinomas will present distant
metastases.
Adenoid cystic carcinomas of the sinonasal tract comprise 20% of all adenoid cystic
carcinomas arising in the head and neck. They are characterized by early spread to
neurovascular structures, submucosal spread, and advanced stage at the time of diagnosis.
Low-grade tumors are defined by a histology with less than 30% solid architecture and
include the cribiform and tubular patterns. High-grade tumors correspond to those with a
histologic pattern more than 30% solid cellular architecture. The incidence of perineural
invasion is similar for both grades, but the incidence of local recurrence and metastases is
higher in the solid type (12). The treatment of adenoid cystic carcinoma of the sinonasal
tract is primarily surgical, although combined surgery and postoperative radiation therapy
seem to yield better local control.
In our experience with 36 patients presenting with adenoid cystic carcinoma of the
sinonasal tract, most patients presented with locally advanced disease (13). The orbit was
invaded in 35% of these patients, and 33% presented with intradural disease. Only two
patients had distant metastasis at the time of diagnosis. Twenty-one of these patients
required a craniofacial resection. Margins are difficult to clear even with extensive
craniofacial resection due to the proximity to vital structures and the propensity for
perineural spread, which in this series was more than 90% of patients. The survival rate at
2 years was 46% for those patients treated primarily in our department and 15% for those
undergoing salvage surgery. Most patients recurred locally (65%), and 50% developed
regional or distant recurrence. The median time to death was 44 months.
Melanoma of the sinonasal tract may be primary or meta-static. Although 20% of all
melanomas originate in the head and neck, less than 1% arise from the sinonasal tract.
They are most commonly found in the nasal cavity, followed by the maxillary sinus,
ethmoid sinus, and frontal sinus, in descending order. Most patients present with disease
confined to the site of origin but show a tendency toward early vascular and lymphatic
invasion. This probably explains the high incidence of local recurrence after surgical
excision. Postoperative radiation therapy may be beneficial, although its impact on
survival and local control has not been addressed in scientific trials. Brandwein et al. (14)
performed a metaanalysis of the English medical literature; the median survival for
patients presenting with sinonasal melanoma was 36 months. The most common cause of
failure, in contrast to the cutaneous variety, is local recurrence.
Olfactory neuroblastoma is a rare tumor arising in the olfactory epithelium. It has a
bimodal frequency at 10 to 20 and 50 to 60 years of age, with a similar incidence in
males and females. Its prognosis is related to the extent of disease and resectability on
initial presentation. Because these tumors usually present in an advanced stage, most
institutions have adopted combined therapies based on the Kadish staging system (Table
105.6). The UCLA classification (Table 105.7), however, seems to provide better
prognostication regarding local recurrences. Factors such as intradural and orbital
invasion are not considered in the Kadish staging system. The advent of craniofacial
resection with or without postoperative radiation therapy has improved the therapeutic
results for early stages.

TABLE 105.6. KADISH STAGING SYSTEM FOR
OLFACTORY NEUROBLASTOMA



TABLE 105.7. UCLA STAGING SYSTEM FOR
OLFACTORY NEUROBLASTOMA



Sinonasal undifferentiated carcinomas are usually composed of small and medium-sized
cells and must be differentiated from rhabdomyosarcomas, melanoma, olfactory
neuroblastoma, lymphoma, and SCCA. The progression of symptoms is very rapid, and
they usually present with very advanced stage involving multiple sinuses. Treatment
comprises trimodal therapy (cyclophosphanaide, doxorubicin, and vincristine), radiation
therapy, and, in appropriate cases, surgery (15). Patients with intracranial disease fared
poorly despite aggressive combination therapy.
Benign Nonepithelial Tumors
Fibroosseous lesions, including osteomas, fibromas, and chondromas, are the most
common benign tumors of the sinonasal tract. Their growth is usually slow and many
times self-limited, making them amenable to observation. Simple surgical excision is
recommended when a histologic diagnosis is needed or to relieve obstructive symptoms.
Sinonasal nerve sheath tumors make up 4% of those arising in the head and neck area
(16). Ninety percent of the nerve sheath tumors show a benign histology. Two thirds of
these tumors are schwannomas and one third neurofibromas. They may present a
diagnostic dilemma, requiring the use of electron microscopy and immunohistochemical
analysis for proper documentation. They are best treated by complete surgical excision,
although partial removal is recommended for massive neurofibromas involving vital
areas.
Malignant Nonepithelial Tumors
Neurogenic sarcomas, contrary to their benign counterparts, are rare in the head and neck
and are most commonly associated with neurofibromatosis. Neurogenic sarcomas are
locally aggressive and frequently present with distant metastases. Surgery plays a primary
role in their therapy; radiation and chemotherapy are usually reserved for incomplete
removal, inoperable cases, or recurrences (16). The 5-year survival rate is around 60%,
although those sarcomas associated with neurofibromatosis behave more aggressively,
yielding a 5-year survival rate around 30% (16).
Rhabdomyosarcomas make up 8% to 19% of the soft-tissue tumors. They arise in the
head and neck in 35% to 45% of cases. In 8% of these patients the rhabdomyosarcoma
originates in the sinonasal tract. These tumors may assume the morphology of any of the
developmental stages of striated muscle, hence the classification into embryonal,
alveolar, and pleomorphic types. The embryonal and alveolar varieties are more common
in children and young adults, whereas the pleomorphic type is more common in adults.
Most data on behavior and therapeutic response of these tumors are based on the
experience with pediatric patients.
Rhabdomyosarcomas of the sinonasal tract are classified as nonorbital parameningeal and
behave more aggressively than those arising in other locations. Systemic and regional
metastasis are common. In 1987, the Intergroup Rhabdomyosarcoma Study I reported the
use of intensive radiation and chemotherapy on patients with nonorbital parameningeal
rhabdomyosarcoma and showed an improvement of the survival rate from 51% to 81%.
In 1993, Intergroup Rhabdomyosarcoma Study II reported further improvements in
survival for those patients with cranial parameningeal involvement (17). Patients with
cranial parameningeal sarcomas but without meningeal invasion received radiation to the
primary tumor plus a 2-cm margin and no intrathecal chemotherapy. Intracranial tumors,
tumors that eroded the base of skull or that caused a cranial neuropathy, were treated with
radiation to the whole cranium and primary tumor site in addition to systemic
chemotherapy and delayed spinal radiation. At 5 years, 67% of patients with class III
disease (gross residual tumor) were alive, compared with 45% in Intergroup
Rhabdomyosarcoma Study I. Surgery may be of benefit for large tumors that remain after
cytoreduction therapy and may be an option for small well-localized tumors. These
results, however, have never been confirmed in adults. Adult rhabdomyosarcoma is
usually treated by wide surgical excision. Radiation is recommended for positive margins
or inoperable or recurrent disease. Chemotherapy has a palliative role that must be
weighed against its possible morbidity.
Fibrosarcoma is a tumor arising from fibroblast; thus, the term encompasses a spectrum
of malignancies that ranges from the low-grade fibromatosis to higher grade tumors.
Misdiagnosis is very common. Radiation and trauma have been implicated as possible
etiologic factors. The treatment of choice is wide surgical excision for previously
untreated tumors. Radiation is recommended for involved margins or recurrent or
inoperable tumors.
Hemangiopericytoma is a highly vascular tumor arising from the pericytes of
Zimmerman. Benign and malignant varieties have been described, although all these
tumors should probably be considered at least low-grade malignancies. They invade
locally and metastasize in 10% to 15% of cases. Sixteen percent are found in the head
and neck, with about 50 reported cases arising in the sinonasal tract (18). Their prognosis
relates to the size of the lesion, number of mitoses, and metastases. The primary
treatment is surgical excision. Radiation and chemotherapy have been used anecdotally
with various results.
Osteogenic sarcoma is the most common primary tumor of bone in the United States,
with an estimated incidence of one case per 100,000 of the general population. Those
originating within the jaws constitute 7% to 10% of all osteosarcomas. Etiologic factors
include ionizing radiation, fibrous dysplasia, trauma, Paget disease, and the gene
associated with retinoblastoma. The most effective therapy is surgical excision. However,
during the past decade several reports have suggested that adjunctive radiation and
chemotherapy may improve survival. A multiinstitutional review and metaanalysis by
Kassir et al. (19) demonstrated a 2- and 5-year disease-free survival for maxillary
osteosarcomas of 65% and 38%, respectively (n = 66). Adjuvant therapy, including
radiation, chemotherapy, or combination therapy, failed to improve the outcome of
patients included in these series. Nonetheless, these authors acknowledge a selection bias
and therefore the role of adjuvant therapy remains unresolved.
Chondrosarcomas are slow-growing tumors that usually arise from cartilaginous
structures. These tumors have been graded from I to III on the basis of the rate of
mitoses, cellularity, and nuclear size. Size of the tumor and grading correlate with the rate
of metastasis, local aggressiveness, and ultimate survival. Surgical removal with wide
margins is the treatment of choice. Gross total removal with postoperative radiation is
recommended for those involving vital structures.
Although the metastatic potential and oncologic outcome of sarcomas arising in the
sinonasal tract is variable among the different histologic types, the local behavior of
sarcomas is similar. Sarcomas are infiltrative, usually advancing to areas farther than
what is appreciated by the naked eye; thus, they are often incompletely resected and
therefore recur locally. Wide excision im-proves the local control, but this is difficult to
perform when dealing with the sinonasal tract, which is adjacent to important if not vital
structures. Our data suggest that cranial base surgery may improve the local control of
sarcomas of the sinonasal tract (20).
Lymphoma of the sinonasal tract is usually of the non-Hodgkin type (21). It is a disease
of the very young or the aging adult. It usually presents with a stage limited to the site of
origin. The treatment includes radiation therapy for localized lesions and chemotherapy
for systemic involvement. The biologic behavior is remarkably different in the pediatric
and adult populations. Adults suffer frequent relapses, commonly involving the ab-
domen, and show a 5-year survival rate of around 45%. In children, complete remissions
are more common, involvement of the gastrointestinal tract is rare, and the 5-year
survival rate is close to 75%. Non-Hodgkin lymphomas are a heterogenous disease with a
disease-free survival rate of 20% to 40% (21).
Extramedullary plasmacytoma is found in the head and neck region in 80% to 90% of the
cases, 40% in the sinonasal tract. It is more common in the sixth to seventh decades. It
tends to spread locally and can be found in the cervical nodes in less than 25% of the
cases. The prognosis is unpredictable, and a variable number of patients will be
diagnosed with multiple myeloma. It is of utmost importance to rule out this diagnosis on
the initial presentation. Most of these lesions will respond to radiation therapy in doses of
4,000 to 5,000 cGy administered over 4 to 5 weeks.
Metastatic Tumors
Metastatic tumors to the sinonasal tract produce symptoms similar to those of primary
tumors. More than 100 cases have been reported, metastasizing to the maxillary, ethmoid,
frontal, and sphenoid sinus in descending order. The most common primary sources are
the kidneys, breasts, and lungs. The treatment is palliative, using radiation, surgery, or
chemotherapy to relieve obstructive and compressive symptoms or pain.
STAGING
A staging system provides a guide to define the extent and prognosis of a tumor and also
serves as a communication tool, allowing different institutions to compare their
experience with the use of different therapeutic modalities. Antral carcinoma has been
included in the American Joint Committee on Cancer TNM staging system (Table 105.8).
The evaluation of the primary tumor is based on Ohngren's observations that tumors
arising below an imaginary line drawn from the medial canthus to the angle of the
mandible (Ohngren line or malignant plane, Fig. 105.1) have a better prognosis than
those arising above this line.

TABLE 105.8. MAXILLARY SINUS TNM
STAGING FOR PRIMARY TUMOR (T)



FIGURE 105.1. Ohngren line extends from the medial
canthus to the angle of the mandible.



The American Joint Committee on Cancer recommends a different system for soft-tissue
sarcomas. This system includes a histologic grading system that differs from the system
used for epithelial tumors. Grading is thought to be the most significant prognostic factor
in patients with mesenchymal tumors and is based on the number of mitoses, degree of
cellularity, amount of stroma, degree of maturation, nuclear pleomorphism, and presence
or absence of necrosis.
PRINCIPLES OF TREATMENT
Surgery
Diagnostic (Biopsy)
Tissue sampling may be performed using endoscopic sinus surgery instruments or
through open transcutaneous or trans-oral procedures (e.g., Caldwell-Luc antrostomy,
external ethmoidectomy, rhinotomy). The former is preferred because it provides good
access and hemostatic control with less morbidity and does not contaminate other soft
tissues.
Drainage/Dbridement
An adequate drainage port (e.g., nasoantral window) should be opened in patients
presenting with secondary bacterial sinusitis and in patients who will require radiation
therapy as primary treatment.
Resection
Surgical resection is usually recommended with curative intent. Palliative excision may
be considered to alleviate intractable pain, to provide rapid decompression of vital
structures, or to debulk a massive lesion, thus freeing the patient from social
embarrassment. Surgery as a single treatment modality for malignant tumors of the
sinonasal tract has yielded 5-year survival rates from 19% to 86% (2,5). Figure 105.2,
Figure 105.3, Figure 105.4, Figure 105.5, Figure 105.6 and Figure 105.7 show the most
common surgical approaches and techniques.

FIGURE 105.2. Medial maxillectomy. Lateral
rhinotomy. A: The skin incision begins beneath the
medial aspect of the eyebrow and continues 4 to 5 mm
anterior to the medial canthus and over the nasal bone
along the deepest portion of the nasomaxillary groove
and following the alar crease. A lip-splitting extension of
the incision is not necessary. To expose the surgical area,
the cheek flap is elevated subperiosteally over the maxilla
and around the infraorbital nerve. The periorbita is elevated over the lamina papyracea,
and the frontoethmoid suture is identified and followed posteriorly until the anterior and
posterior ethmoid arteries are identified. B: The anterior wall of the antrum is penetrated
at the canine fossa using a 4-mm chisel. The antrostomy is enlarged with a Kerrison
rongeur around the infraorbital nerve and superiorly toward the inferior orbital rim. Bone
is removed across the orbital rim, including the lacrimal fossa. C: The nasolacrimal duct
is divided and the lacrimal sac is opened and marsupialized. D: Osteotomies and removal
of the specimen. The first osteotomy involved in the actual removal extends through the
piriform aperture at the level of the nasal floor, directed posteriorly until the osteotomy
perforates the posterior wall of the antrum. E: The orbit is retracted laterally, and a
second osteotomy is performed at the frontoethmoid suture, extending posteriorly to a
point 2 to 3 mm posterior to the posterior ethmoid artery (i.e., anterior to the optic
foramen). The thin bone of the medial floor of the orbit is sawed following a line that
joins the lacrimal fossa with the superior osteotomy. The final bone cut involves three
steps. First, a 2-mm osteotome is introduced through the anterior antrostomy and directed
through the medial posterior antral wall. The osteotome is advanced superiorly to reach
the level of the superior osteotome and is then pushed medially. Second, a wide
osteotome, introduced through the nose, is impacted into the anterior wall of the sphenoid
sinus and then pushed laterally. Heavy right-angle scissors (e.g., upper lateral cartilage
scissors) are guided through the inferior osteotomy with one blade in the nose and the
other in the antrum to start the posterior cut, behind the turbinates. F: Heavy curved
scissors are then introduced with one blade in the nasal cavity and the other in the
superior osteotomy, directed through or along the posterior attachments of the turbinates.
The specimen is removed by anterior and inferior traction. Hemostasis is achieved by
direct clamping or cautery. The bony edges are smoothed with a rongeur. Residual
ethmoid mucosa is removed with ethmoid forceps, and a wide sphenoidotomy is opened
with Kerrison rongeurs. The cavity is covered with Gelfoam for hemostasis. The medial
canthal tendon is sutured to the periosteum of the nasal bones. The wound is closed using
a meticulous layered closure. AEF, anterior ethmoidal foramen; OF, optic foramen; PEF,
posterior ethmoidal foramen.



FIGURE 105.3. . A and B: A transfixion incision is
performed at the membranous septum and is extended
laterally to join a transcartilaginous incision. C: A
gingivobuccal incision is performed, extending laterally
from the midline to the maxillary tuberosities. D: In
exposing the surgical area, tenotomy scissors are
introduced through the transcartilaginous incisions to
dissect the skin from the nasal skeleton. The dissection
over the maxilla is carried out in a subperiosteal plane. This dissection joins the nasal
degloving using sharp dissection over the piriform aperture attachments. The dissection is
extended superiorly exposing the midface skeleton. E: The exposure is limited by the
infraorbital neurovascular bundles. The osteotomies, removal of the specimen,
reconstruction, and closure are performed as described for the lateral rhinotomy.



FIGURE 105.4. Total maxillectomy. A total
maxillectomy with preservation of the orbit can be
performed using incisions identical to lateral rhinotomy
incisions with a lip-splitting extension. Alternatively, a
lateral rhinotomy incision may be combined with an
ipsilateral degloving approach. A: If increased exposure
is necessary, the facial incisions may be modified. The
superior incision begins at the lateral canthus and extends
medially, passing 3 to 4 mm below the ciliary line. The eye is protected by a temporary
tarsorrhaphy stitch. This incision may be substituted by a transconjunctival incision. The
subciliary limb is joined to a lateral rhinotomy incision. The orbicularis oculi muscle is
incised with an inferiorly directed slant, exposing the orbital septum. The gingivobuccal
incision is extended laterally to the ipsilateral maxillary tuberosity. B: The soft palate is
incised at the junction with the hard palate, and its attachments are sharply transected.
The mucoperiosteum of the hard palate is incised following a paramedian line ipsilateral
to the lesion. The paramedian strip of mucosa will be later imbricated over the bony edge
of the hard palate to facilitate the fitting of a prosthesis. C:. The orbital contents are
dissected from the medial inferior and lateral walls, exposing the lacrimal sac, the
anterior and posterior ethmoid arteries, and the infraorbital fissure. These are managed as
described for a medial maxillectomy (Fig. 105.2). Osteotomies and removal of the
specimen. D: The body and frontal process of the zygoma are divided with the saw. The
maxilla is severed from the nasal bones with the saw, and the osteotomy is extended
superiorly to the frontoethmoidal suture. A superior osteotomy is carried out posteriorly
to a point 3 to 4 mm posterior to the posterior ethmoid artery. An osteotomy is performed
connecting the lateral and medial wall osteotomies across the inferior orbital fissure. The
hard palate is transected with a Gigli or sagittal saw. The maxilla is disattached from the
skull by tapping a chisel placed into the pterygomaxillary fissure in a posterosuperior
direction. The superior attachments of the turbinates are sharply severed as for a medial
maxillectomy (Fig. 105.2). The specimen is removed by anteroinferior traction.
Remnants of ethmoid sinus mucosa are removed in a piecemeal fashion. The coronoid
process of the mandible is removed to avoid displacement of the prosthesis when opening
the mandible. E: The exposed facial and pterygoid muscles and periorbita are lined with
a split-thickness skin graft that is 0.35 to 0.45 mm thick. E: The obturator or denture is
wired to the remaining dentition or suspended from the zygomatic arch and piriform
aperture or lag screwed to the remaining hard palate. F: A medial canthopexy using a Y-
shape titanium plate fixed to the nasal bones. A figure 8 nonabsorbable suture is used to
medialize the medial canthal tendon. G: The floor and medial walls of the orbit are
reconstructed with titanium mesh. This is then covered by a vertically split temporalis
muscle flap. The anterior half is used for the reconstruction and the posterior half is
transposed to the anterior temporal fossa to obliterate the defect.



FIGURE 105.5. Orbital exenteration. A: Incisions for
orbital exenteration include those described earlier and a
supraciliary incision along the upper eyelid. These
incisions allow the preservation of the lids, which can be
used to line the remaining orbital cavity. If the eyelids are
involved by the tumor, the incisions are modified to
include their resection en bloc. The exposure proceeds as
previously described (Fig. 105.4), omitting the dissection
of the orbit from the inferior wall. The upper eyelid is retracted superiorly, and the
periorbita is incised over the superior orbital rim. The orbit is dissected from the superior
wall, identifying optic foramen and superior orbital fissure. These are infiltrated with
lidocaine to block the autonomic innervation and prevent cardiac arrhythmias. The neural
and vascular structures traveling through these foramina are transected after hemostasis
with bipolar cautery or clamping. Inferior traction on the globe allows further
visualization of the orbital floor and inferior orbital fissure. Lateral and medial wall
osteotomies are connected as in Fig. 105.4D. Other osteotomies are identical to Fig.
105.4D. B: The roof of the orbit may be lined with a skin graft or left to granulate and
mucosalize. Alternatively, the cavity may be filled with a temporalis muscle flap. It
should be remembered that squamous epithelium tolerates trauma (e.g., prosthesis) better
than mucosa. In exposing the surgical area, the facial flap is elevated subperiosteally. In
the case of extension through the anterior wall of the antrum, the facial flap may be
elevated in a subcutaneous plane, including the facial musculature in the specimen. The
skin may also be resected en bloc, to address direct invasion by the tumor. The dissection
is carried out along the lateral wall of the maxilla and the internal maxillary artery is
identified at the pterygomaxillary fissure and clipped.



FIGURE 105.6. Inferior maxillectomy. Tumors confined
to the floor of the antrum may be managed by partial
maxillectomy. It differs from total maxillectomy on the
preservation of the orbital floor and in selected cases of
the infraorbital nerve. Bilateral maxillectomy: the
procedure is performed bilaterally as in Fig. 105.4. The
nasal septum may be sacrificed or preserved for
suspension of the prosthesis or reconstructive flaps.



FIGURE 105.7. Pathways of invasion include (1) direct
bony erosion (e.g., medial wall or floor), (2) perivascular
or perineural invasion (e.g., infraorbital or ethmoidal
neurovascular bundles), and (3) preformed pathways
(e.g., infraorbital fissure, nasolacrimal duct).



Rehabilitation
The main goals of postsurgical rehabilitation are primary wound healing, preservation or
reconstruction of the facial contour, and restoration of oronasal separation, thus
facilitating speech and swallowing. Functional considerations take precedence over
aesthetics. Rehabilitation after surgical resection may be achieved with a dental
prosthesis or reconstructive flaps, such as temporalis muscle flaps with and without the
inclusion of cranial bone, pedicled or microvascular free myocutaneous flaps (e.g.,
pectoralis major, latissimus dorsi, trapezius), and cutaneous flaps (e.g., forehead, scalp,
deltopectoral). Flaps are recommended to replace resected skin, to provide support for the
orbit or brain, or to isolate the cranial cavity from the upper aerodigestive tract.
As a general rule, the surgical defect after a total maxillectomy should not be obliterated
at the initial operation; an open cavity facilitates cleansing and allows direct visual
inspection during the follow-up period. Patients who require a craniofacial resection,
especially those needing an orbital exenteration, deserve special consideration, because a
recurrence after an adequate craniofacial resection is uniformly lethal. From the
functional standpoint, these patients require immediate separation of the cranial cavity
from the upper aerodigestive tract and support of the brain. These goals frequently can be
achieved with a pericranial flap and transfer of a temporalis muscle flap. The temporalis
muscle, however, is often devascularized after an infratemporal fossa dissection or its
bulk may be inadequate to obliterate the dead space. Under these circumstances, the
maxillectomy cavity may be obliterated with a free microvascular flap, offering
immediate palliation and oronasal separation without the need for an prosthesis. This
latter consideration becomes more important if the patient is completely edentulous or if
the maxillectomy extends beyond midline that makes difficult the retention of a
prosthesis or in patients who cannot care for a prosthesis.
Radiation Therapy
The response of sinonasal tract tumors to radiation varies with the stage and histology of
the tumor. Radiation may be used as a single modality, as an adjunct to surgery, or as
palliative therapy (22). Radiation therapy is the primary treatment for lymphoreticular
tumors, for patients who are poor surgical candidates, and for those patients who refuse
surgery. Preoperative and postoperative radiation therapy seems to produce similar
results. We favor postoperative radiation because there is a smaller volume of tumor cells
to kill, the margins of the nonradiated tumor can be better defined during surgery, and
postoperative wound healing is more predictable.
Chemotherapy
The role of chemotherapy for the treatment of tumors of the sinonasal tract is usually
palliative, using its cytoreductive effect to relieve pain, obstruction, or to debulk a
massive external lesion. Nevertheless, the failure of combination therapy, including
surgery and radiation, to achieve local control, the need for deforming procedures, or the
shifting of cause of failure to distant metastases spearheaded the use of systemic and even
topical chemotherapy in multimodal therapy protocols. These reports, however, are very
limited in nature, including small number of patients, and the studies are usually
nonrandomized. Thus, the impact on survival, local control, and development of distant
metastases remains undefined (Table 105.9). Patients at high risk for recurrence such as
those presenting with positive margins, perineural spread, or extracapsular spread in
regional metastasis and those who represent a poor surgical risk and those who refuse
surgery should be considered for enrollment in protocols that include combinations of
radiation and chemotherapy.

TABLE 105.9. TREATMENT TUMORS OF THE
SINONASAL TRACT



Treatment by Site of Origin
Here we discuss the treatment of SCCA by site of origin. The management of other
epithelial and mesenchymal malignancies was discussed in the pathology section.
Nasal Cavity
Tumors arising in the nasal cavity become symptomatic at earlier stages than tumors
arising in the paranasal sinuses. Nasal tumors produce obstructive symptoms, bleeding, or
a nasal mass that prompt the patient to seek evaluation. This is of clinical importance
because earlier diagnosis has been associated with a better prognosis.
SCCA is the most common malignant tumor, constituting more than half of the tumors in
this area. Tumors arising at the floor, lateral wall, and septum are all amenable to surgical
excision. Tumors extending to the paranasal sinuses, those larger than 2 cm, and those
associated with positive surgical margins have been associated with a poor prognosis for
which postoperative radiation should be considered. Most series report a 5-year survival
rate of above 60%.
Maxillary Antrum
The maxillary sinus is the most common site of origin for malignancies of the sinonasal
tract. Early-stage SCCA may be treated by surgery or radiation. However, SCCA is
usually diagnosed at advanced stages for which combination therapy seems more
successful. Survival diminishes with the stage of the tumor, and complete surgical
resection is required for success. The overall 5-year survival rate in large series range
between 40% to 50%.
Ethmoid Sinus
Tumors originating in the ethmoid sinuses, like those in the nasal cavity, produce
symptoms at early stages, leading to earlier diagnosis and better prognosis. SCCA
continues to be the most common histologic diagnosis, but adenomatous carcinomas are
more common than at other areas (Table 105.10). Improved imaging techniques and the
use of anterior craniofacial resection (see the discussion below on management of
advanced tumors of the base of skull) have improved the prognosis of previously
unresectable tumors. Combined therapy with radiation is recommended for advanced
stages, positive surgical margins, and recurrent tumors. The overall 5-year survival rate
seems to be 50% to 60% (23,24).

TABLE 105.10. MALIGNANT TUMORS OF THE
ETHMOID SINUS



Sphenoid Sinus
Primary malignancies of the sphenoid sinus are extremely rare, making up less than 1%
of malignant sinonasal tumors. En bloc surgical resection is technically and functionally
very difficult due to the anatomic relationships of the sphenoid sinus. Gross total removal
and postoperative radiation therapy is the treatment of choice for most of these tumors.
Although the benefits of surgical debulking are debatable, at the very least it will provide
a wide sphenoidotomy for drainage and dbridement during radiation therapy. The
overall prognosis at 5-year follow-up varies from 5% to 25%.
Frontal Sinus
Tumors arising in the frontal sinus, like sphenoidal tumors, are rare. The anatomic site,
however, is more amenable to surgical resection. These tumors may be managed
similarly to ethmoidal tumors.
MANAGEMENT OF ADVANCED TUMORS
Orbital Invasion
Sinonasal tract tumors may extend to the orbit by invasion or erosion of the bony walls,
by perineural or perivascular invasion, or by following preformed pathways (Fig. 105.7).
Patients with orbital invasion rapidly develop ocular symptoms, such as proptosis,
diplopia, decreased visual acuity, diminished motility, chemosis, lid edema, and epiphora.
CT provides better definition of the bony erosion than plain films, but it is not reliable in
ascertaining invasion of the soft tissues. Although MRI better clarifies this problem,
possible invasion must be confirmed during surgery.
There seems to be general agreement, however, that bone erosion does not constitute an
absolute indication for orbital exenteration (25). The prognosis of patients with invasion
of the periorbita is dismal; therefore, palliation is a more realistic goal (Table 105.11).
Some authors believe that preoperative radiation improves the possibility of orbital
preservation. However, the use of adjunctive radiation therapy, before or after surgery,
did not yield an improved prognosis in any of these series. Ophthalmic sequelae can be
aggravated by radiation.

TABLE 105.11. META-ANALYSIS OUTCOME:
INVASION OF ORBIT (NED)



Resection of the medial and inferior orbital walls produces severe enophthalmos and
hypophthalmos, which is aggravated by resection of the periorbita. We favor rigid
reconstruction of the bony orbit using titanium mesh with or without calvarial bone
grafts, which is then covered with a local, regional, or microvascular flap. To better
restore the orbital anatomy and to prevent lagophthalmos due to ectropion, the lateral
canthus should be reattached to the corresponding anatomic site of insertion (Whitnall
tubercle). Ectropion, however, may still occur due to fibrosis. The medial wall is usually
resected as part of the oncologic surgery, requiring that the medial canthus is reattached
to a titanium plate, as illustrated in Fig. 105.4.
Cervical Metastasis
The incidence of nodal metastasis on initial presentation varies from 3% to 16%, with
most series reporting an incidence around 10%. Nodal metastases at the time of initial
presentation indicates a grim prognosis. An increased incidence of nodal metastases has
been reported in patients with tumors extending to the oral mucosa, but this finding has
been refuted by others. The low incidence of nodal metastasis from sinonasal
malignancies does not justify the use of elective neck dissection or radiation. The
presence of cervical node metastasis on initial presentation does not seem to be a
contraindication for radical treatment of the primary.
The presence of cervical metastasis during the course of the disease is higher, varying
from 5% to 44%, and is most common during the first 48 months after treatment.
Recurrence in the form of cervical metastasis ranks second after local recurrence as a
cause for treatment failure. However, an isolated recurrence to cervical nodes is rare;
usually it is accompanied by recurrent disease at the primary site.
Pterygopalatine Fossa
The incidence of PtPF invasion by sinonasal tract malignancies varies from 10% to 20%.
The presence of tumor in this area is considered a risk factor for local recurrence. Despite
the difficulty of an en bloc resection of this area, several authors have designed
approaches with sound oncologic principles, obtaining variable results.
It is difficult to draw valid conclusions from these reports because of a small number of
patients, limited follow-up, and the heterogeneity of patients. The impact on the survival
and local recurrence rate of bone, neural, and vascular invasion in the PtPF has not been
elucidated. Radical surgical resection in combination with radiation therapy, however, is
advised for patients with PtPF invasion.
Infratemporal Fossa and Skull Base
The skull base, like the orbit, may be involved by tumor by direct invasion and bone
erosion, by preformed pathways (e.g., cribriform plate, superior orbital fissure, foramen
lacerum), or by following neural or vascular structures (e.g., V2, V3). The overall
incidence of skull base invasion by sinonasal malignancies appears to be about 15%.
The anterior or anterolateral craniofacial resection is a well-established procedure for
sinonasal tumors invading the anterior skull base or requiring en bloc resection of this
region as a margin (Fig. 105.8). The anterior craniofacial resection may be extended
laterally to join a temporal craniotomy to include the pterygoid plates, the PtPF, the
infratemporal fossa, and the floor of the middle cranial fossa en bloc. Absolute
contraindications for craniofacial resection are medical or nutritional problems that would
eliminate the patient as a surgical candidate, presence of distant metastases, invasion of
the prevertebral fascia, invasion of the cavernous sinus by a high-grade malignancy,
involvement of the carotid artery in a high-risk patient (as determined by carotid flow
studies), and bilateral invasion of the optic nerves or optic chiasm. Although technically
feasible, resection of these areas is associated with an unacceptable morbidity and
mortality rate, offers no significant palliation, and does not appear to improve survival.
Relative contraindications include invasion of the dura and intracranial involvement of
neural structures by adenoid cystic carcinoma. These situations have a poor prognosis,
but in selected cases cra-niofacial resection may offer significant palliation or local
control.

FIGURE 105.8. A: Bicoronal flap incision. B: The scalp
flap is dissected anteriorly in a subperiosteal plane and
laterally just above the superficial layer of the deep
temporal fascia. Leaving the pericranial flap attached to
the scalp flap prevents desiccation of the flap during the
procedure. C: To expose the supraorbital rim, superior
orbital cavity, and nasal bones, the supraorbital
neurovascular bundle is mobilized from its notch or
foramen. D: Orbital, cranial, and zygomatic osteotomies are performed according to the
required exposure. The tumor is resected en bloc with the anterior or middle fossa skull
base. E: A pericranial flap is elevated and placed under the dura of anterior lobe and over
the remaining bone of the anterior fossa. The craniotomy and orbital bone grafts are
replaced above the pericranial flap, which separates the cranial cavity from the upper
aerodigestive tract.



Improvements in the preoperative mapping of tumors with CT and MRI and the use of
more reliable vascularized flaps for the reconstruction of the skull base have improved
the surgical mortality and morbidity. However, the overall 5-year survival rate appears
unchanged at 50% to 60%.

COMPLICATIONS
Orbital
Surgical
The nasolacrimal duct is sacrificed during the performance of a maxillectomy, and
subsequent stenosis of the lacrimal sac opening may lead to epiphora. A
dacryocystorhinostomy at the time of definitive resection is an effective way to prevent
this complication. Cannulation of the lacrimal canaliculi for 12 weeks is recommended
for cases of recurrent stenosis or when the lacrimal sac is resected.
Limitation of movement of the extraocular muscles may occur after trauma to the muscle
or its motor innervation or upon entrapment in the craniofacial osteotomies. The latter
complication should be managed by urgent surgical release. Limitations of extraocular
muscle movement due to edema or neuromuscular contusion should be managed
expectantly. Diplopia may be alleviated by alternating eye patching.
The optic nerve may be compressed during the mobilization of the specimen or during
craniofacial resection. High-dose steroids and emergent surgical decompression are
recommended.
Enophthalmos or hypophthalmos usually develop due to the loss of the inferior orbital
and/or medial support. Reconstructive techniques were previously discussed.
Radiation Therapy
The incidence of radiation complications in patients with orbit preservation is close to
100% (Table 105.12). The field included in the radiation portals for sinonasal tract
tumors usually includes the anterior and posterior orbital segment. The anterior segment,
including the eyelids, conjunctiva, lacrimal gland and apparatus, cornea, lens, and the rest
of the anterior chamber, may be spared by the using shields and lateral fields. When the
orbit is involved by the tumor, however, irradiation of the entire eye is usually necessary,
and these structures therefore are at risk.

TABLE 105.12. EFFECTS OF RADIATION ON THE
EYE



Thus, complications of the anterior globe are common with full eye irradiation. A dry eye
will decompensate rapidly, leading to severe keratitis, panophthalmitis, and blindness
within 1 year. Enucleation is recommended for uncontrolled panophthalmitis or a painful
eye.
If the anterior segment can be spared, patients will most likely experience delayed (3 to 5
years) loss of vision secondary to postradiation retinopathy or optic neuropathy. Although
the retina and optic nerve are radioresistant, their microvasculature is not. Other
conditions affecting the microvasculature or that potentiate the effect of the radiation,
such as chemotherapy, diabetes mellitus, and atherosclerosis, may have an additive
effect. The incidence of these complications is related to total dose and fractionation. The
tolerance limit seems to be around 5,000 cGy with fractions of 200 cGy. Although they
are rare below 3,500 cGy, their incidence is 50% to 65% with 6,000 to 7,000 cGy and
above 85% with 8,000 cGy. Nevertheless, the degree of visual impairment cannot be
accurately predicted and has been reported with doses considered within the safe limits.
The incidence of bilateral blindness, although rarely reported, may be as high as 8% and
is related to the irradiation of the contralateral posterior segment. However, the dose
should not be compromised to diminish the complication rate if the attempted goal is
cure. Conformal radiation therapy reduces the percentage of radiation received by normal
tissue and may decrease the incidence of optic nerve and optic chiasm complications.
Wound Complications
Wound complications include bleeding, infection, and loss of reconstructive flaps or skin
grafts (Table 105.13 and Table 105.14). Postoperative infection is rare. Cellulitis should
be treated with antibiotics providing broad-spectrum coverage adjusted to the culture and
sensitivity results. Venous retrograde seeding, or even direct spread in the presence of a
cerebrospinal fluid (CSF) fistula can lead to meningitis or intracranial abscess. A CT
followed by a lumbar puncture is indicated if meningitis is suspected. Formation of crusts
within the nasal cavity is a common problem and may lead to infection. Frequent
irrigations with normal saline solution helps with nasal hygiene.

TABLE 105.13. COMPLICATIONS
SINONASAL TRACT TUMORS



TABLE 105.14. EMERGENCIES SINONASAL
TRACT TUMORS



The loss of a reconstructive flap is accompanied by necrosis and overgrowth of bacteria
and is best treated by dbridement and aggressive local care. A secondary reconstruction
must be postponed until the defect is free of infection. However, flaps providing coverage
to vital areas (e.g., carotid artery, brain) must be replaced by another vascularized flap as
soon as possible. Loss of minor areas of a skin graft is usually of no consequence,
because secondary epithelialization occurs rapidly. Loss of the entire skin graft, however,
may lead to scarring and contraction of the cavity, healing by mucosalization, and
problems in fitting a prosthesis. Treatment of local infection and dbridement of necrotic
tissue, followed by regrafting with internal and external splinting of the skin graft, may
remedy this problem.
Skull Base Complications
Skull base complications include CSF leak, meningitis, intracranial abscess, tension
pneumocephalus, and osteomyelitis. These complications are most commonly the result
of technical errors (e.g., loss of a reconstructive flap). Infectious complications are
surprisingly uncommon, considering that skull base resection involves exposure of the
cranial cavity to aerodigestive tract flora. Treatment includes empiric intravenous
antibiotics with broad-spectrum coverage, including the skin and aerodigestive flora. The
antibiotics are later adjusted to the culture and sensitivity results. Further contamination
or exposure of the intracranial contents to the sinonasal tract should be curtailed by the
use of vascularized flaps. Free bone grafts that become infected during the early
postoperative period should be removed. Late osteomyelitis or osteoradionecrosis may be
managed with antibiotics and dbridement limited to the affected bone. Hyperbaric
oxygen treatment may be beneficial in patients with osteoradionecrosis. Intracranial
abscess requires open drainage and intravenous antibiotics.
Tension pneumocephalus is treated by percutaneous aspiration and diversion of the nasal
airway. The latter may be accomplished with the use of an endotracheal tube, nasal
trumpets, or a tracheotomy.
EMERGENCIES ASSOCIATED WITH SINONASAL TUMORS
Bleeding
Friable or vascular tumors may lead to profuse bleeding when traumatized (e.g., biopsy),
or bleeding may occur spontaneously after desiccation and breakdown of the blood
vessels in the tumor. Mild to moderate bleeding is managed using the principles of
treatment for anterior and posterior epistaxis. Cauterization or packing is recommended.
In the case of a massive tumor that completely occludes the nasal passages, thus making
adequate packing impossible, angiography and embolization should be considered. This
technique is also useful in vascular tumors, providing prompt hemostasis and facilitating
surgical removal. If circumstances preclude the use of this technique, a transoral ligation
of the internal maxillary artery and transorbital ligation of the ethmoidal arteries may
control the bleeding. Ligation of the external carotid artery, although not as effective as
internal maxillary artery ligation, may be necessary if the transoral approach is
impossible. One should remember, however, that ligation of the external carotid artery
will eliminate the possibility of embolization. A combination of these techniques may be
required to prevent exsanguination. Uncontrollable hemostasis from a known malignancy
may require emergency maxillectomy.
Vision Impairment
Sinonasal tumors may lead to blindness due to compression or stretching of the optic
nerve, its arterial supply, or its venous drainage. Emergent treatment of the tumor may be
necessary to prevent blindness, although it will be a moot point if the eye is going to be
ultimately sacrificed. Lymphoreticular tumors may be treated with radiation.
Unresectable solid tumors may be debulked and the orbit or the optic nerve
decompressed.
Infection
Tumors of the sinonasal tract may obstruct sinus drainage and lead to acute bacterial
sinusitis and possible orbital and intracranial complications. Secondary sinus infections
must be treated with antibiotics, providing broad aerobic and anaerobic coverage.
Surgical drainage by endoscopic or open technique is usually required.
Cerebrospinal Fluid Leak or Pneumocephalus
CSF leak or pneumocephalus may occur after destruction of the skull base and disruption
of the dura mater (e.g., cribriform plate). CSF leaks are less likely to resolve
spontaneously under these circumstances and therefore should be managed by prompt
craniofacial resection, dural grafting, and a pericranial flap. Patients must be kept on bed
rest while awaiting the operation. The use of prophylactic antibiotics is controversial.
They may seem indicated in the presence of a necrotic tumor, but prolonged treatment
may lead to colonization with resistant flora that will be more difficult to eradicate in
case of meningitis. In the presence of a CSF fistula, the tumor may have a ball-valve
effect, leading to tension pneumocephalus and symptoms of increased intracranial
pressure. This complication may be treated by transcutaneous needle aspiration.

HIGHLIGHTS
Malignant tumors of the sinonasal tract constitute less than 1%
of all malignancies.
The most common clinical presentation of sinonasal tumors
includes symptoms that are undistinguishable from
inflammatory sinus disease, namely, nasal airway obstruction,
pain, and epistaxis. Abnormal V
1
and/or V
2
sensation strongly
suggest the possibility of a tumor.
CT or MRI is an essential component of evaluation,
establishing the extent and vascularity of the tumor and its
relationship to neurovascular structures.
An understanding of the variable natural history of tumors of
the sinonasal tract is crucial to patient counseling and treatment
planning. A wide variety of histologies may be encountered,
although SCCA is most common.
Rehabilitation after surgical resection may be accomplished by
the use of prosthodontics or reconstructive flaps.
Radiation is a common adjuvant to surgery for patients with
SCCA. The response of sinonasal tract tumors to radiation
therapy varies with the stage and histology of the tumor.
Bony erosion of the orbital walls does not constitute an
indication for orbital exenteration.
Patients with tumor involvement of the skull base, either in the
infratemporal fossa or at the fovea ethmoidalis and cribriform
plate, should be considered for craniofacial resection.
CHAPTER REFERENCES
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1972;86:255.
2. Frazell E, Lewis JS. Cancer of the nasal cavity and accessory sinuses: a report on the management
of 416 patients. Cancer 1963;16:1293.
3. Spiro JD, Soo KC, Spiro RH. Squamous carcinoma of the nasal cavity and paranasal sinuses. Am J
Surg 1989;158:328.
4. Tabb HG, Barranco SJ. Cancer of the maxillary sinus. Laryngoscope 1971;81:818.
5. Jackson RT, Fitzhugh GS, Constable WC. Malignant neoplasms of the nasal cavities and
paranasal sinuses (a retrospective study). Laryngoscope 1977;87:726.
6. Snyderman CH, Carrau RL, DeVries. Carotid artery resection: update on preoperative evaluation.
In: Johnson JT, Derkay CS, Mandell-Brown MK, et al., eds. Instructional Courses. Vol. 6. St.
Louis, MO: Mosby, 1993:341344.
7. Hyams VJ. Papillomas of the nasal cavity and paranasal sinuses: a clinicopathological study of
315 cases. Ann Otol Rhinol Otolaryngol 1971;80:192.
8. Myers EN, Fernau JL, Johnson JT, et al. Management of inverted papilloma. Laryngoscope
1990;100:481.
9. Waitz G, Wigand ME. Results of endoscopic sinus surgery for the treatment of inverted
papillomas. Laryngoscope 1992;102:917922.
10. Bridger MWM, Beale FA, Bryce DP. Carcinoma of the paranasal sinuses: a review of 158 cases. J
Otolaryngol 1978;7:379.
11. Cheng VST, Wang CC. Carcinoma of the paranasal sinuses. Cancer 1977;40:3038.
12. Goepfert H, Luna MA, Lindberg RD, et al. Malignant salivary gland tumors of the paranasal
sinuses and nasal cavity. Arch Otolaryngol 1983;109:662.
13. Pitman K, Prokopakis E, Aydogan B, et al. The role of skull base surgery for the treatment of
adenoid cystic carcinoma of the sinonasal tract. Head Neck 1999;21:402407.
14. Brandwein MS, Rothstein A, Lawson W, et al. Sinonasal melanoma. A clinicopathologic study of
25 cases and literature meta-analysis. Arch Otolaryngol Head Neck Surg 1997;123:290296.
15. Deutsch BD, Levine PA, Stewart FM, et al. Sinonasal undifferentiated carcinoma: a ray of hope.
Otolaryngol Head Neck Surg 1993;108:697700.
16. Hillstrom RP, Zarbo RJ, Jacobs JR. Nerve sheath tumors of the paranasal sinuses: electron
microscopy and histopathologic diagnosis. Otolaryngol Head Neck Surg 1990;102:257.
17. Maurer HM, Gehan EA, Beltangady M, et al. The Intergroup Rhabdomyosarcoma Study-II.
Cancer 1993;71:19041922.
18. Harv Alsamad A, Beautru R, Gaston A, et al. Management of sinonasal hemangiopericytomas.
Rhinology 1999;37:153158.
19. Kassir RR, Rassekh CH, Kinsella, et al. Osteosarcoma of the head and neck: meta-analysis of
treatment outcomes. Laryngoscope 1997;107:5661.
20. Carrau RL, Segas J, Nuss DW, et al. Role of skull base surgery for local control of sarcomas of the
nasal cavity and paranasal sinuses. Eur Arch Otorhinolaryngol 1994;251:350356.
21. Abbondanzo SL, Wenig BM. Non-Hodgkin's lymphoma of the sinonasal tract. A
clinicopathologic and immunophenotypic study of 120 cases. Cancer 1995;45:12811291.
22. Cellini N, DeSantis M, Mantello G, et al. Radiation therapy of cancer of paranasal sinuses: a
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Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

106 ORBITAL TUMORS
Head & Neck SurgeryOtolaryngology
106




ORBITAL TUMORS
MARK A. ALFORD
JEFFREY A. NERAD

M.A. Alford: Department of Oculoplastic Surgery, Ophthalmology Associates, Fort Worth, Texas.
J.A. Nerad: Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.


Vascular Tumors
Cavernous Hemangioma
Capillary Hemangioma
Lymphangioma
Hematopoietic Tumors
Lymphoid Tumors
Leukemia
Langerhans Cell Histiocytosis (Histiocytosis X)
Neural Tumors
Schwannoma (Neurilemoma)
Optic Nerve Gliomas
Orbital Meningiomas
Mesenchymal Tumors
Mesodermal and Muscle Tumors
Fibroosseous Tumors
Lacrimal Gland Tumors
Inflammatory Tumors
Cysts
Secondary Tumors
Metastatic Tumors
Conclusion
Chapter References
Wide varieties of tumors are known to occur in the orbit. Vascular, lymphoid, nervous,
and mesenchymal structures are all normally found within the orbit and may give rise to
primary orbital tumors. Primary lacrimal gland tumors of lymphoid and epithelial cell
origin also cause orbital mass lesions. In Henderson's (1) 40-year study of orbital tumors
at the Mayo Clinic, the five most common primary tumors were hemangioma, non-
Hodgkin lymphoma, inflammatory tumors, meningioma, and optic nerve glioma. Wilson
and Grossniklaus (2) reviewed five large series on orbital disease with a total of 4,563
orbital lesions. They found that neoplasms (primary and secondary), inflammations
(Graves disease, idiopathic orbital inflammation and infections), and other lesions
composed 50%, 25%, and 25%, respectively, of the reported orbital lesions. The most
common primary orbital tumors in their review were meningioma, cavernous
hemangioma, and lymphoma.
The close anatomic proximity of the orbit to other important structures, including the
paranasal sinuses, cranium, conjunctiva, lacrimal sac, eyelids, and globe, makes
secondary invasion another common cause of orbital tumors. Secondary tumors account
for approximately 12% of all orbital lesions (2) and 33% to 45% of all orbital neoplasms
(1,3). The most common secondary tumors were mucoceles, squamous cell carcinoma,
meningioma, vascular malformations, and basal cell carcinoma (1).
Metastatic disease, particularly adenocarcinoma of the lung and breast, may also produce
orbital lesions. Between 2% and 8% of orbital tumors are due to metastatic disease (1,4).
In addition to neoplasms, various inflammatory and systemic vasculitic conditions may
produce orbital masses.
The incidence of orbital tumors has been studied in several long-term series. Henderson
(1) found the five most common tumor groups from a series of 1,376 consecutive orbital
tumors to be carcinomas (23%), cysts (12%), meningioma (10%), vascular tumors (9%),
and non-Hodgkin lymphoma (8%). Shields (4), in a study of 645 orbital biopsies, found
the most common orbital tumors to be cystic lesions (30%), inflammatory masses (13%),
lacrimal fossa lesions (13%), secondary tumors (11%), lymphoid tumors (10%), and
vasculogenic tumors (6%).
An assortment of orbital tumors affects pediatric patients. In reported series, the exact
percentages of tumors in the pediatric age group varies. However, some general patterns
are clear. Most pediatric tumors are benign. Depending on the study, between 10% and
30% of childhood orbital tumors are malignant (1,5). Among the most common benign
lesions are orbital dermoids, vascular tumors (capillary hemangioma and lymphangioma),
optic nerve glioma, and inflammatory tumors. The most common malignant orbital tumor
of children is rhabdomyosarcoma. Metastatic neuroblastoma, leukemic orbital
involvement (granulocytic sarcoma), Ewing sarcoma, and extension of retinoblastoma
from the globe also produce malignant orbital tumors in children.
The orbital contents are arranged in a highly organized and efficient manner with little
extra room available, so almost all space-occupying lesions of the orbit produce signs and
symptoms. Proptosis, the protrusion of the eye or eyes secondary to an orbital space-
occupying lesion, is the most important clinical manifestation of orbital disease (Fig.
106.1; see also Color Plate 39 following p. 1898). The characteristics of the proptosis
including direction, onset, duration, and laterality are important and may aid in diagnosis.
The direction of the proptosis is often described as axial versus nonaxial. Axial proptosis
often occurs due to tumors inside the extraocular muscle cone (intraconal space).
Nonaxial proptosis favors an extraconal position, such as the medial and inferior
diplacement of the globe secondary to a lacrimal gland tumor.

FIGURE 106.1. Proptosis. A patient with left-sided
proptosis secondary to a metastatic orbital tumor. (See
also Color Plate 39 following p. 1898.)



In general, inflammations and infections of the orbit present with acute proptosis over
hours to days. Dysthyroid orbitopathy, rhabdomyosarcoma, lymphomatous lesions, and
some malignant tumors have a more subacute presentation and course, worsening over a
period of days. Benign tumors and cysts and some malignant tumors have a chronic
course, with proptosis worsening over months to years.
Ocular motility disturbances and diplopia are common findings in orbital disease. The
tumor may infiltrate the extraocular muscle or the nerve supplying the muscle, producing
diplopia secondary to a motility deficit. The space-occupying tumor may also displace
the globe from its normal position, causing double vision. Other signs and symptoms
include vision changes, conjunctival injection and chemosis, pain, and pupillary changes.
Prompt and accurate diagnosis in addition to proper treatment can prevent loss of vision,
improve motility disturbances, and in some cases increase the chances of patient survival.
The goal of this chapter is to provide an overview of the most commonly encountered
orbital tumors. Typical presenting characteristics and common clinical findings of each
tumor are discussed to aid the otorhinolaryngologist in formulating a differential
diagnosis when encountering orbital tumors.
VASCULAR TUMORS
Vascular tumors are among the most commonly encountered orbital tumors in both
children and adults. Vascular tumors represent approximately 10% of all orbital tumors
(2). Most vascular tumors of the orbit are benign, with cavernous hemangioma, capillary
hemangioma, and lymphangioma being the most common lesions.
Cavernous Hemangioma
Cavernous hemangioma is the most common primary intraconal orbital neoplasm found
in adults (6). In the Mayo Clinic study, cavernous hemangiomas were found to represent
4.3% of all orbital tumors (1). This benign tumor is more common in women and
typically presents in the third to fifth decade of life. Alfred and Char (6) found that 70%
of their patients with cavernous hemangiomas were women with a mean age of 41 years
at the time of diagnosis. Their patients ranged in age from 18 to 67 years old.
Slowly progressive, painless, unilateral proptosis over many years is the typical
presentation of patients with cavernous hemangiomas of the orbit. Significant vision loss
is uncommon. Although multiple and even bilateral tumors have been reported,
cavernous hemangiomas are most frequently found as isolated masses. Computed
tomography (CT) and magnetic resonance imaging (MRI) findings have been shown to
yield the proper diagnosis in about 95% of cases. On CT or MRI, the tumor is seen as a
discrete round or oval mass without associated inflammation or infiltration of
surrounding orbital structures. In 88% of cases, the tumor is located within the intraconal
space (6). The tumor usually enhances with intravenous contrast. Histopathologic
examination reveals an encapsulated tumor composed of multiple, large, blood-filled
vascular channels lined by flattened endothelial cells.
The treatment of choice is complete surgical excision of the tumor and capsule. The
prognosis for patients with cavernous hemangiomas is excellent. Recurrences are very
rare even with incomplete resection. The typical intraconal location generally requires a
lateral orbitotomy for complete surgical removal. In rare apical lesions, a transcranial
approach may be required.
Capillary Hemangioma
Capillary hemangioma is the most common vascular tumor of the orbit and periocular
tissues in infancy and childhood. This benign proliferation of endothelial cells is
extremely common, and at least one lesion can be found on some part of the body in
approximately 1% to 2% of all newborns. The typical superficial bright red strawberry
mark on the eyelid or periocular skin may be an isolated finding or may be associated
with orbital involvement. Deeper lesions may appear more bluish. The upper eyelid is the
most common periocular location, often producing blepharoptosis. Orbital hemangiomas
frequently produce proptosis and globe displacement. Approximately 5% of capillary
hemangiomas are solely intraorbital, showing minimal, if any, cutaneous eyelid
involvement (7).
The natural history of these lesions is well known. The capillary hemangioma is generally
not present at birth, is first noted during the first month of life, and grows to its maximum
size by 12 to 18 months of age. A period of stabilization occurs, followed by spontaneous
involution by age 4 to 8 years old. Fifty percent will involute by age 5, and approximately
90% are resolved by 7 years of age (4). There is, however, significant morbidity from
these lesions because of the tumor's presence during the important period of ocular and
facial development that occurs during the first decade of life. Eyelid tumors have the
potential to cause deprivational and anisometropic amblyopia. Amblyopia is defined as
decreased visual acuity in a structurally normal eye due to incomplete visual system
development, which can occur only during the first few years of life. Hypertrophy and
stretching of the epidermal and subcutaneous tissues can lead to cosmetic cutaneous
deformities. Orbital capillary hemangiomas can cause proptosis with corneal exposure,
amblyopia and strabismus, optic atrophy, and bony malformations of the orbit and face.
Diagnosis is usually made on the basis of the clinical examination. Orbital involvement is
best evaluated with CT or MRI. Orbital imaging shows a diffusely infiltrating
nonencapsulated mass (Fig. 106.2). Capillary hemangiomas tend to conform to the
surrounding orbital structures. The tumor enhances with intravenous contrast on both CT
and MRI studies, confirming the lesion's vascularity. Bony erosion is not seen, but
expansion of the orbital walls caused by the tumor's mass is possible. Orbital
ultrasonography is also a valuable noninvasive test showing a variable pattern of high and
low reflectivity.

FIGURE 106.2. Postenhancement T1-weighted magnetic
resonance image showing a capillary hemangioma of the
right orbit in a neonate. Note the infiltrative nature of the
tumor and the increased size of the orbit.



Lesions not affecting visual or orbital development can be observed during regression as
the child ages. Indications for treatment include amblyopia, proptosis with corneal
exposure, optic nerve compression, and bony deformities. In many cases, the patient's
parents are eager for any treatment to remove the undesirable lesion as soon as possible.
The various treatment options for eyelid and orbital lesions include intralesional
injections of corticosteroids, systemic corticosteroids, or careful debulking surgeries.
Complete surgical removal is typically not possible.
Lymphangioma
Lymphangiomas are benign vascular malformations that may affect the ocular adnexa
and orbit. They likely arise from pluripotent mesodermal tissue of the orbit and
surrounding structures capable of forming vascular or lymphatic structures.
Lymphangiomas are hemodynamically isolated from the normal orbital circulation.
Histopathologically, the tumor is made up of multiple, variably sized, thin-walled,
endothelial-lined vascular channels.
Rootman et al. (8) have described the location of orbital and periocular lymphangiomas
as being superficial, deep, or a combination of the two. In most cases, the tumor is
identified during the first decade of life. Superficial lesions are more common and
involve the conjunctiva and eyelids. Tumors in this location have a better prognosis for
good vision than do the deeper lesions. Orbital and eyelid lymphangiomas may also
present as a soft bluish mass of the eyelid. Orbital lesions present with sudden proptosis
or persistent variable proptosis. The sudden onset of proptosis is due to hemorrhage
within one of the tumor's vascular channels. This spontaneous hemorrhage has been
called a chocolate cyst. If vision is not affected, these bleeds are observed.
Lymphangiomas are also known to enlarge in size after an upper respiratory tract
infection, resulting in increased proptosis. There is no enlargement of the lesion with a
change in head position or with a Valsalva maneuver.
Diagnosis of lymphangioma is typically made with orbital imaging studies in conjunction
with the clinical presentation. CT shows multiple, contiguous, dilated cystic spaces
within the orbit. The radiodensity of the lobules varies with the amount of fluid and blood
in each cyst (8). The cysts typically do not enhance, but rim enhancement is possible. In
cases identified later in childhood, enlargement of the bony orbit is seen. MRI is likely
the better study for orbital lymphangioma, allowing detailed examination of the tissue
planes and cysts.
A dilated orbital vessel or varix is often confused with a lymphangioma. A varix is
typically an isolated lesion that becomes symptomatic gradually. A varix is connected to
the normal circulation and thus enhances with intravenous contrast and enlarges with a
Valsalva maneuver.
Management of orbital and periocular lymphangioma is difficult. The infiltrative nature
of these tumors makes complete resection impossible. The morbidity associated with
these tumors may be quite high in some cases. Significant proptosis, corneal exposure,
and optic nerve compression are all potential causes of visual loss in these patients.
Surgical debulking and cyst drainage are the mainstays of treatment. Complete surgical
removal is rarely possible. Other treatment options of systemic corticosteroids and
radiotherapy have shown only limited results and are not recommended.
HEMATOPOIETIC TUMORS
Lymphoid Tumors
The tumors of lymphoid origin that are found in the orbit present a spectrum of disease
from the benign reactive lymphoid hyperplasia to the more worrisome atypical lymphoid
hyperplasia to frankly malignant orbital lymphoma. Interestingly, the orbit does not
contain lymph nodes or well-defined lymphatic vasculature, but lymphoid lesions are one
of the most common orbital tumors. Lymphoid lesions of the orbit represent between 4%
and 13% of all orbital tumors (2).
Orbital lymphoid lesions may be isolated to the orbital tissues or associated with systemic
lymphoma. Approximately 50% of orbital lymphomas are localized to the orbit at the
time of diagnosis. Approximately 15% to 25% of patients with benign reactive lymphoid
hyperplasia and up to 40% of patients with atypical lymphoid hyperplasia will develop
systemic lymphoma (9). Of the patients with a monoclonal malignant lymphoma of the
orbit, at least one third will develop systemic disease over time. The location of the
original orbital or periocular lymphoma is important in systemic prognosis.
Approximately 20% of patients with lymphoid tumors of the conjunctiva developed
systemic lymphoma, whereas 35% of patients with orbital tumors and 67% of patients
with eyelid disease eventually developed systemic lymphoma (9). Bilateral lesions
suggest systemic disease.
Orbital lymphoid lesions occur almost exclusively in adults. Most patients are between
50 and 70 years old, and there is a slight female predominance. The benign and malignant
lymphoid lesions present with similar findings. Most patients present with slowly
progressive painless proptosis usually occurring over several weeks to a few months.
These tumors are frequently located in the anterior orbit, and often a mass can be
palpated along the orbital rim. The lesion may also be visible under the intact conjunctiva
as a smooth, rounded, pink-orange mass (salmon patch) (Fig. 106.3; see also Color
Plate 40 following p. 1898).

FIGURE 106.3. Orbital lymphoma extending under the
conjunctiva of the right eye. (See also Color Plate 40
following p. 1898.)



CT shows the characteristic putty-like molding of the tumor around other orbital
structures. The tumor has a rather homogeneous appearance with clearly defined borders
in most cases. Bony destruction is not a typical finding. Most tumors are extraconal, with
the superior orbit being the most common location. The lacrimal gland is involved in
about 40% of cases. An affected lacrimal gland shows a smooth enlargement of its
normal shape compared with the more globular or rounded enlargement seen in primary
lacrimal gland neoplasms.
A generous biopsy specimen of a suspected lymphoid lesion is needed for definitive
diagnosis. A portion of the biopsy specimen should be submitted to the pathologist in
formalin for routine permanent section. Fresh tissue must also be submitted for
sophisticated immunohistochemical studies that are required for precise cell surface
marker typing for clonality. Most orbital lymphomas are of monoclonal B-cell origin.
Most of the reactive orbital lymphoid lesions are composed of a majority of T cells and B
cells with different cell-surface markers (polyclonal). All patients with lymphoid lesions
of the orbit need a complete systemic evaluation by an oncologist, searching for systemic
lymphoma. The workup should include a physical examination, complete blood count,
bone marrow aspiration and biopsy, lumbar puncture, and abdominal and chest CT.
Treatment is dictated by the type of lymphoid lesion and whether there is evidence of
systemic disease. Patients with isolated reactive lymphoid hyperplasia typically receive
low doses of radiotherapy to the affected orbit. Isolated atypical lymphoid hyperplasia
and lymphoma are treated with higher doses of radiation. Patients with systemic disease
receive a combination of orbital radiotherapy and systemic chemotherapy.
Leukemia
The orbit is just one of many sites that can harbor malignant leukemic cells during the
course of the disease. Approximately 10% of patients with systemic leukemia were found
to have orbital involvement at the time of autopsy (1). Orbital involvement is more
common in children and is often bilateral. Signs of orbital disease include a rapid onset of
proptosis and inflammation that may resemble an orbital cellulitis. Spontaneous orbital
hemorrhage has also been reported in association with leukemia.
A granulocytic sarcoma is a collection of immature myeloid cells, forming an obvious
mass in the orbit. Historically, the tumor has been called a chloroma due to the greenish
color observed when the tumor is biopsied. The pigment responsible for the distinctive
color is myeloperoxidase. Granulocytic sarcomas are more common in children and may
be seen in both acute and chronic myelogenous leukemias (10). In some cases, the
granulocytic sarcoma precedes systemic leukemia. The most common presenting findings
are painless proptosis often accompanied by a violaceous lid swelling of a few weeks'
duration. As with all children with progressive proptosis, orbital imaging must be
obtained urgently. In patients with an orbital granulocytic sarcoma and no sign of
systemic leukemia, systemic chemotherapy is started, because all patients will eventually
develop true systemic leukemia. In patients with preexisting leukemia, radiotherapy is
often used to treat the orbital lesions. The prognosis for patients with granulocytic
sarcoma is bleak, with most patients dying within 18 months of diagnosis.
Langerhans Cell Histiocytosis (Histiocytosis X)
Langerhans cell histiocytosis is a rare condition of proliferating Langerhans cells. The
Langerhans cell is a macrophage that normally resides in the epidermis of the skin. The
disease is characterized by one or more destructive bone lesions of the skull, ribs,
sternum, long bones, vertebrae, or pelvis. In the disseminated form of the disease, soft-
tissue granulomas are also present. The orbit is rarely affected, with only 11 cases
reported in the long-term Mayo Clinic study of orbital tumors (1). Most patients with
Langerhans cell granulomas are children under 10 years of age. The common findings
include unilateral proptosis and lateral eyelid swelling. These symptoms usually progress
over a period of months. Some children present with more rapid onset of symptoms,
mimicking an orbital cellulitis. The frontal and zygomatic bones are the most commonly
involved orbital structures (11).
The CT appearance of this condition is quite distinctive, showing a circumscribed lytic
bone lesion without sclerosis. Early in the disease, the bone appears expanded by a
sharply delineated radiolucent mass. Histopathologic examination re-veals the
macrophage and giant cells along with a mixture of inflammatory cells.
Excision of isolated orbital bone lesions is often curative. There are also reports of
spontaneous healing after biopsy. Some investigators favor postoperative radiotherapy as
well. In general, the behavior of these tumors is unpredictable, and close follow-up is
required. Treatment of patients with disseminated disease is more difficult. Treatment
usually includes radiotherapy in combination with chemotherapy.
NEURAL TUMORS
The most common primary orbital tumors of neural origin include schwannoma, optic
nerve glioma, meningioma, and neurofibroma and represent approximately 8% of all
orbital tumors (1).
Schwannoma (Neurilemoma)
The schwannoma is a benign, noninvasive, peripheral nerve tumor accounting for
approximately 1% of all orbital tumors. Schwannomas occur primarily in adults ranging
in age from 20 to 70 years (4). The patient typically presents with slowly progressive
painless proptosis and diplopia. Although uncommon, progressive visual loss or a relative
afferent pupillary defect may be caused by tumors located in the orbital apex.
Most schwannomas are unilateral and solitary. They may arise from any nerve within the
orbit. They are more commonly located in the intraconal space but may be found in any
part of the orbit. CT examination shows a well-circumscribed elongated ovoid mass that
displaces surrounding structures (Fig. 106.4). The lesion is commonly homogeneous.
Long-standing tumors, so-called ancient schwannomas, may have areas of cystic
degeneration and calcification. Schwannomas show a small degree of enhancement after
intravenous contrast injection. On MRI, the tumor is hypointense on T1-weighted and
hyperintense on T2-weighted images.

FIGURE 106.4. Orbital schwannoma located in the
lateral portion of the left orbit in a 51-year-old man. Note
the round shape and homogeneous appearance on
computed tomography.



Histopathologic examination reveals an encapsulated tumor composed principally of
Schwann cells. The Schwann cells are usually arranged as a combination of two
distinctive patterns separated by variable degrees of fibrous tissue. The Antoni A pattern
consists of an orderly palisading arrangement of elongated spindle-shaped cells. The
Antoni B pattern is composed of a loose myxoid arrangement of ovoid or stellate cells
(1).
The definitive therapy for orbital schwannomas is the complete surgical excision of the
tumor and its capsule. The prognosis is excellent, with recurrences being extremely rare
(12).
Optic Nerve Gliomas
The optic nerve glioma is the fifth most common primary intraorbital tumor, representing
2.4% of all orbital mass lesions in the Mayo Clinic study (1). It is also the second most
common orbital tumor found in children, accounting for approximately 14% of orbital
tumors in patients less than 15 years old (1). The fibrillary astrocyte is the cell
responsible for optic nerve gliomas. Optic nerve gliomas are associated with
neurofibromatosis in 18% to 50% of cases (13).
Most patients present in the first decade of life, with a mean age of approximately 8 years
old. Intraorbital optic nerve gliomas present with axial proptosis and vision loss.
Frequently, young children do not report vision changes. Loss of vision in a child should
be suspected if strabismus or a relative afferent pupillary defect develops. Optic nerve
head edema is present early, with pallor present in long-standing disease. Gliomas located
in the optic canal or chiasm may present initially with vision loss as the only finding. On
CT, optic nerve gliomas appear as fusiform or lobular, isodense, homogeneous
enlargements of the optic nerve (Fig. 106.5). On coronal section, the nerve cannot be
separated from the tumor mass, and calcification is rare. MRI is the study of choice to
evaluate extension of the tumor into the optic canal and chiasm. The glioma is
hypointense relative to brain on T1-weighted images and hyperintense on T2-weighted
images.

FIGURE 106.5. T1-weighted magnetic resonance image
of an optic nerve glioma of the left orbit in a 12-year-old
girl.



Treatment of optic nerve gliomas depends on the location of the tumor, the visual acuity,
and its growth pattern. Wright et al. (13) concluded that the growth pattern of optic nerve
gliomas falls into two fairly distinct groups. The first is one of indolent growth with little
change in tumor size on serial examinations over many years. The other is a pattern of
progressive tumor enlargement. Optic nerve meningiomas, although typically less
common in children, are more aggressive than optic nerve gliomas and should be ruled
out in the case of a rapidly growing optic nerve mass. Patients with tumors confined to
the orbit along with good vision can be followed closely with sensitive neuroophthalmic
testing and serial imaging studies. Evidence of continued growth or extension into the
optic canal dictates complete resection of the optic nerve from the posterior surface of the
globe to the optic chiasm. Patients with poor vision at presentation typically have the
tumor and optic nerve removed via a transfrontal craniotomy for definitive diagnosis and
complete resection.
Orbital Meningiomas
Primary orbital meningiomas arise from the optic nerve and represent approximately 3%
of all orbital tumors (1). Of all the meningiomas found in the orbit, about 30% are
primary. Most (70%) of the meningiomas of the orbit invade secondarily from the
cranium and are discussed later in this chapter in the section on secondary tumors.
Approximately 75% of patients with meningiomas are female (14). The disease is most
common in adults in the fourth to seventh decade of life. Rarely, optic nerve
meningiomas are seen in children.
Although proptosis is the most common presenting sign, seen in roughly 85% of patients
with primary orbital meningiomas, visual disturbances such as decreased visual acuity
and visual field defects are the more common chief complaints voiced by patients. Other
findings include optic disk pallor, optic nerve head edema, diplopia, headaches,
optociliary shunt vessels, and ptosis. On CT, a primary optic nerve meningioma appears
as either a focal exophytic mass at any point along the optic nerve or more commonly as
a fusiform enlargement of the nerve. The mass is typically homogeneous, infiltrative, and
enhancing. In some cases, calcifications of the tumor in the subarachnoid space along the
optic nerve tissue give the classic railroad track appearance. On coronal views, the
normal-sized optic nerve is visible and surrounded by the tumor. As in optic nerve
gliomas, MRI is the study of choice to evaluate evidence of intracranial extension.
In general, optic nerve sheath meningiomas cannot be removed from the surface of the
optic nerve without causing severe vision loss. In many cases, especially in older patients,
these tumors can be simply followed for evidence of intracranial extension. Radiotherapy
and hormone therapy are also used in some patients. Wright et al. (14), after following 50
patients for over 15 years, found that optic nerve meningiomas in patients less than 40
years old were more aggressive. They believed the chance of intracranial spread is
considerable in these patients and recommended total excision of the tumor at an early
stage.
MESENCHYMAL TUMORS
Mesodermal and Muscle Tumors
Rhabdomyosarcoma
Rhabdomyosarcoma is the most common primary malignant tumor of the orbit in
children and the most common soft-tissue malignancy of childhood (4).
Rhabdomyosarcoma has been diagnosed in patients ranging in age from newborn to 70
years old. The average age at presentation is 6 to 7 years old, with 90% of patients under
the age of 13 years (4,15). There appears to be a slight male predominance and no racial
predilection or known hereditary tendency (4).
Children typically present with progressive, painless, unilateral proptosis of a period of
days to weeks. About one third of children also present with ptosis and a palpable mass
(5). The eyelid skin may be edematous and erythematous, but unlike preseptal cellulitis,
the skin is not warm to the touch. Other ophthalmic findings may include conjunctival
chemosis, ophthalmoplegia, choroidal folds, optic disk edema, or dilated retinal vessels.
If the tumor originated in or has spread to the paranasal sinuses, symptoms of sinusitis
and epistaxis may be present.
CT shows a poorly defined homogeneous orbital mass (Fig. 106.6). The tumor may arise
from any location within the orbit, with about 25% being intraconal (1). Areas of bony
destruction and sinus invasion may be present.

FIGURE 106.6. Computed tomography of
rhabdomyosarcoma of the left posterior orbit in a 6-year-
old girl. Note the area of bony destruction.



The tumor arises from primitive mesenchymal cells in the orbit. Three types of
rhabdomyosarcoma have been described. Two thirds of pediatric orbital cases are of the
embryonal type. The alveolar type is the most malignant form and has a predilection for
the inferior orbit. The pleomorphic type is the most well-differentiated form and carries
the best prognosis.
Biopsy is required for definitive diagnosis before treatment. The surgical approach should
depend on the extent and accessibility of the tumor determined by the clinical
examination and radiologic findings. At the time of biopsy, the largest amount of tumor
that can be safely removed is taken. Fresh tissue should be sent for immunohistochemical
studies. Exenteration or complete resection is not required. In biopsy-proven cases,
staging and assessment of disseminated disease with bone marrow biopsy, chest
radiographs, liver function tests, complete blood count, and lumbar puncture are required.
In the past, the disease was uniformly fatal. Recent advances in the treatment of
rhabdomyosarcoma using a combination of chemotherapy and radiation have increased
the 5-year survival rate in localized disease to approximately 90% (15). With
disseminated disease, the 5-year survival decreases to 35%.
Fibroosseous Tumors
Fibrous Dysplasia
Fibrous dysplasia is an uncommon condition considered to be a hamartomatous
malformation of unknown etiology. The condition is characterized by the replacement of
normal cortical bone with a cellular fibrous stroma containing multiple nests of immature
woven bone. The disease is described as monostotic when a bone or bones at a single
location are involved and as polyostotic when multiple bones at different locations are
affected. Orbital and facial bone involvement is more typical of the monostotic form of
the disease. Orbital bone involvement may affect only one or multiple contiguous bones
but typically remains unilateral. The orbital roof is the most common site of orbital
involvement (16). The polyostotic form, which has been associated with Albright
syndrome in a small number of cases, may affect the bones of the face but more
commonly involves the ribs, sternum, and vertebrae.
The onset of the disease is typically seen in the first two decades of life. However, in
some patients, the lesions are not symptomatic until much later in life. The signs and
symptoms depend on which bones are involved. The most common presentation is an
adolescent patient with proptosis, globe and orbit displacement, and facial asymmetry.
Patients with sphenoid bone involvement may present with decreased visual acuity or
visual field defects. Involvement of the maxilla may lead to upward globe displacement,
nasolacrimal duct obstruction, and epiphora.
On CT, the involved bone appears thickened and deformed. Within the thickened bone
are multiple areas of lucent-appearing lytic spaces and ground glass-appearing sclerotic
zones (16). The thinner orbital bones have a cystic appearance, whereas thicker bones
typically appear more sclerotic (1). Although the clinical presentation is usually adequate
to make the diagnosis in a child, biopsy specimens are sometimes required for diagnosis.
It was once thought that spontaneous arrest of the disease occurred by the third decade of
life. However, in some cases, progression continues into later adulthood. Although many
cases can be managed with careful observation, indications for treatment include
significant cosmetic deformity and vision loss secondary to compressive optic
neuropathy. Treatment is surgical, with complete resection followed by immediate
craniofacial reconstruction (16). In larger tumors where total resection is not possible,
removal of as much of the involved bone as necessary to protect sight and correct the
cosmetic deformity should be performed.
Osteoma
An osteoma is a benign tumor of bone accounting for approximately 1% of all orbital
tumors (4). Osteomas are also known to arise from the bones of the paranasal sinuses.
The presentation depends on the bony origin of the tumor. Most osteomas affecting the
orbit originate from the frontal bone, with ethmoid and maxillary osteomas being less
commonly associated with orbital findings.
Osteomas are typically unilateral solitary lesions recognized in adulthood. In patients
with multiple lesions, Gardner syndrome, a familial condition associated with soft-tissue
tumors and colon carcinoma, must be ruled out. Patients with osteomas present with
symptoms including sinusitis, dull orbital pain, facial asymmetry, globe displacement, or
proptosis. Diagnosis is readily made with CT or plain films showing a smooth, rounded,
or lobulated mass with a density similar to normal bone. The lesions may appear sessile
or pedunculated.
Smaller asymptomatic tumors are typically followed with serial CT and clinical
examinations. Larger tumors causing significant proptosis or tumors in the orbital apex
compressing the optic nerve often need to be resected. The prognosis for life and vision is
excellent.
Osteosarcoma
Osteosarcoma is a highly malignant tumor of bone that more commonly affects the long
bones of the body but in rare cases involves the bones of the face and orbit. Recently, a
gene responsible for the development of both osteosarcoma and retinoblastoma has been
discovered on chromosome 13 (17). Patients present with a more rapid progression of
proptosis and globe displacement when compared with benign bony tumors. Orbital pain,
numbness, and vision loss have also been found to be common findings. In Henderson's
(1) study of 10 patients, the median age at presentation was 41 years with a range from 16
to 64 years old. CT studies show an enhancing bony mass with areas of sclerosis and
lysis of bone. Areas of calcification are also seen, representing an area of new bone
formation. On histopathologic examination, proliferating malignant cells are mixed with
areas of immature bone.
The prognosis for patients with osteosarcoma of the orbital region is extremely poor. The
treatment of choice at the present time is surgical resection along with systemic
chemotherapy. However, the highly malignant nature of these tumors and the difficulty in
complete resection of tumors in this area makes a cure unlikely.
LACRIMAL GLAND TUMORS
Numerous conditions are known to cause enlargement of the lacrimal gland. Mass lesions
of the lacrimal gland typically produce proptosis and medial and inferior globe
displacement. Most lacrimal gland masses are due to idiopathic orbital inflammatory
disease and are associated with other inflammatory signs and symptoms. The findings of
swelling and erythema of the lateral portion of the upper eyelid suggest inflammation of
the lacrimal gland. Bacterial and viral infections of the lacrimal gland may also cause an
acute dacryoadenitis. Staphylococcal and streptococcal species are the most common
bacterial pathogens affecting the lacrimal gland. Viral dacryoadenitis may be seen in
association with herpesvirus infections, mumps, and mononucleosis. Chronic
dacryoadenitis is caused by trachoma, syphilis, tuberculosis, and sarcoidosis.
Of the lacrimal gland masses not associated with infectious or inflammatory conditions,
approximately half are caused by lymphoproliferative disorders and half by epithelial
neoplasms.
The lymphoid lesions affecting the lacrimal gland include benign reactive lymphoid
hyperplasia, atypical lymphoid hyperplasia, malignant lymphoma, and the leukemias. On
CT examination, lymphoid lesions produce smooth enlargement and elongation of the
lacrimal gland, whereas epithelial neoplasms appear more globular. Lymphoid lesions
appear to mold around orbital structures and rarely show any bony changes (18).
Approximately 50% of all epithelial tumors of the lacrimal gland are benign mixed
tumors (pleomorphic adenomas). The other 50% are carcinomas, including adenoid cystic
carcinoma, malignant mixed carcinoma, and adenocarcinoma. Primary epithelial
neoplasms of the lacrimal gland are rare, representing about 3% of all orbital tumors (2).
The benign mixed tumor of the lacrimal gland accounts for approximately 25% of all
lacrimal fossa masses (4). It is composed of proliferations of both epithelial and
mesenchymal elements. The tumor occurs primarily in adults ranging in age from 20 to
50 years old. Patients present with slowly progressive painless proptosis, globe
displacement, and upper eyelid swelling over a period of months to years. In many cases,
a nontender firm mass can be palpated at the orbital rim. CT examination shows a round
well-circumscribed mass in the anterior portion of the superior lateral orbit (Fig. 106.7).
Pressure enlargement of the lacrimal gland fossa without bony destruction by this slow-
growing tumor is almost always present.

FIGURE 106.7. Computed tomography of a large, long-
standing, benign mixed tumor of the lacrimal gland in a
90-year-old patient. Significant globe indentation is
present. Corneal exposure secondary to the tumor led to a
severe corneal infection and loss of the eye.



Patients presenting with findings consistent with a benign mixed tumor should undergo
complete surgical excision of the tumor and its pseudocapule through a lateral orbitotomy
without a preliminary incisional biopsy. If the capsule is incised for direct biopsy or if the
tumor is incompletely removed, there is a 32% rate of recurrence over the patient's
lifetime, often with malignant degeneration of the tumor (18).
Adenoid cystic carcinoma is the most common malignant epithelial neoplasm of the
lacrimal gland, representing about 25% of all epithelial neoplasms. Malignant mixed cell
carcinomas, adenocarcinomas, and mucoepidermoid carcinomas are also found. Patients
with malignant epithelial tumors of the lacrimal gland typically present with progressive
proptosis of less than 12 months' duration. Pain or numbness is a very common finding
and should always alert the physician to the possibility of a malignant process.
Radiologic studies frequently show bony destruction associated with an enlarged lacrimal
gland mass infiltrating the surrounding soft tissues. Calcification of the lesion is also
more likely in malignant lesions (18).
Malignant epithelial lesions of the lacrimal gland represent a serious threat to survival,
with mortality being greater than 50%. In suspected malignant lesions, incisional biopsy
is indicated for definitive diagnosis. Malignant lesions require complete surgical
resection. In many cases, this is achieved with exenteration, removal of adjacent bone,
and postoperative radiotherapy. Distinct metastases may occur many years after excision
of the primary tumor.
INFLAMMATORY TUMORS
Idiopathic orbital inflammation, also known as orbital pseudotumor, is an inflammatory
condition of unknown etiology affecting various orbital tissues. In the Mayo Clinic series,
idiopathic orbital inflammation constituted 4.2% of all orbital tumors and 10% of all
primary orbital tumors (1). The inflammation can be diffuse or localized to specific
orbital tissues, including the extraocular muscles (myositis), the lacrimal gland
(sclerosing dacryoadenitis), the sclera (scleritis), or the optic nerve (perineuritis).
Idiopathic orbital inflammation has been seen in patients of all ages but is most common
in adults between the ages of 30 and 70 years old. The onset of symptoms typically
occurs over a period of a few days, but more subacute and chronic forms have been
described. Most patients present with dull and poorly localized orbital pain often
exacerbated by eye movement. Proptosis is noted in 67% to 85% of patients, indicating
the inflammation of retrobulbar tissues (19). Other common findings include eyelid
swelling, conjunctival chemosis, and diplopia (Fig. 106.8; see also Color Plate 41
following p. 1898). Vision loss is reported in about 20% of patients secondary to scleral,
uveal, or optic nerve inflammation (20). Approximately one third of children have
bilateral disease. Bilateral disease in an adult suggests a systemic vasculitis or
lymphoproliferative disorder.

FIGURE 106.8. An inflamed right eye associated with
idiopathic orbital inflammation. The patient complained
of pain with eye movement and diplopia. (See also Color
Plate 41 following p.1898).



CT findings vary depending on the orbital tissues involved. Affected structures are
typically enlarged, with shaggy margins surrounded by a diffuse hazy infiltrate.
Enhancement is frequently noted after intravenous contrast injection. In general, multiple
tissues of the orbit are affected, and this finding is highly suggestive of idiopathic orbital
inflammation. Solitary mass lesions are reported but rare. In idiopathic orbital
inflammation affecting the extraocular muscles, the belly of the muscle and the muscle
tendon is involved. The muscle enlargement seen in thyroid-related orbital disease spares
the tendon. Bony destruction is uncommon. MRI is also useful in the evaluation of
idiopathic orbital inflammation. T1-weighted images show the lesions to be isointense to
muscle and enhance with contrast. T2-weighted images are isointense to hyperintense to
the surrounding orbital fat.
Biopsy specimens commonly show a diffuse cellular infiltrate composed of granulocytes,
lymphocytes, plasma cells, and at times eosinophils. Varying degrees of fibrosis are also
present. Vasculitis is not a finding consistent with idiopathic orbital inflammation.
Most patients with idiopathic orbital inflammation respond well to oral corticosteroids. A
small number of cases may require more powerful immunosuppressive medications, such
as cyclophosphamide or cyclosporine, or radiotherapy. In young otherwise healthy
patients in whom idiopathic orbital inflammation is the most likely diagnosis from
clinical and radiologic findings, an empiric trial of oral prednisone is acceptable. The
response is typically dramatic, with significant improvement occurring during the first
few days of therapy. Biopsy is required if the response to steroids is poor or incomplete
or if the patient rebounds during the steroid taper.
Orbital vasculitis is a rare and poorly understood cause of orbital inflammation associated
with many of the systemic vasculitic syndromes. The initial findings may be similar to
those found in idiopathic orbital inflammation. Wegener granulomatosis, polyarteritis
nodosa, giant cell arteritis, and many of the conditions causing hypersensitivity vasculitis,
including systemic lupus erythematosus, are known to cause orbital inflammation. Most
patients with orbital involvement present with painful proptosis and other systemic
symptoms of vasculitis. In some cases, orbital findings may be the first indication of
disease. The common feature found on a biopsy specimen is evidence of vasculitis. As
discussed earlier, suspected idiopathic orbital inflammation that does not respond as
expected to oral prednisone demands a biopsy for histologic examination. The early
diagnosis of a systemic vasculitic condition may slow the progression of the disease and
spare vital organs.
CYSTS
A variety of cysts is known to occur in the orbit. The most commonly encountered
primary cysts are the dermoid and the simple epithelial cyst. The mucocele is the most
common secondary orbital cyst and is discussed in the section on secondary orbital
tumors. Dermoid and epithelial cysts accounted for approximately 2% of all orbital
tumors in the Henderson (1) series and as high as 25% of all orbital tumors in the Shields
(4) series. The difference is likely due to the fact that the Shields study also included
dermoids of the anterior orbital rim and deep orbital lesions.
Dermoid cysts likely arise from bits of embryonic ectoderm trapped within the suture
lines between the orbital bones. The superficial dermoid cysts are located most
commonly at the frontozygomatic, frontoethmoid, or frontolacrimal sutures (21). The
deep orbital dermoids are commonly adjacent to the sphenozygomatic or sphenoethmoid
suture. Most superficial dermoid cysts are diagnosed before the age of 5 years, whereas
deeper cysts can be asymptomatic until adulthood. The clinical presentation is dependent
on the location of the cyst. Patients with anteriorly located dermoid cysts present with a
unilateral, painless, palpable, subcutaneous mass most commonly located at the lateral
portion of the eyebrow. Cysts located at the orbital rim are typically attached to the
orbital bone by a small pedicle of tissue. These cysts are not attached to the overlying
skin. Deeper orbital lesions present with painless progressive proptosis and globe
displacement. In the cases of a spontaneous rupture, an acute inflammatory reaction
develops.
CT shows a round, well-defined, thin-walled structure with a nonenhancing lumen (21).
Some cysts are more irregularly shaped with less well-defined walls and cystic spaces
(Fig. 106.9). Some cysts, especially those found in the deeper orbit of older patients, may
show calcium deposition in the cyst wall and bony changes secondary to the pressure
effect of the tumor. In rare cases, the cysts take on a dumbbell shape as they extend
through the suture into the temporalis fossa, sinuses, or cranial vault. Microscopic
examination reveals a cystic structure lined by stratified squamous epithelium along with
the presence of dermal appendages, including hairs and sebaceous glands.

FIGURE 106.9. Dermoid cyst. On this computed
tomography, note the mass between the lateral rectus
muscle and the lateral wall on the right side.



Small dermoid cysts can be followed for signs of growth, visual disturbances, or cosmetic
deformity. Larger symptomatic cysts are managed with complete surgical excision
without rupture of the cyst wall. The prognosis for vision is excellent for anteriorly
located cysts. More posterior cysts are more difficult to remove completely and carry a
slightly higher rate of recurrence.
Simple epidermal cysts are less common than dermoid cysts, representing about 1% of all
orbital tumors (4). They typically appear in a slightly older age group than dermoid cysts.
They likely occur because of sequestrations of conjunctival tissue in the orbit during
embryologic development or are implanted after trauma. Most patients present with
slowly progressive painless proptosis. Sometimes a mass can be palpated in the upper
eyelid. Proptosis can be rapid and associated with eyelid swelling and erythema if the
cyst ruptures. CT shows a thin-walled cystic structure without bony involvement. The
preferred treatment is complete surgical excision.
SECONDARY TUMORS
Tumors arising from the structures surrounding the orbit are common causes of orbital
mass lesions, accounting for 44% of all orbital tumors in the 40-year study of orbital
tumors at the Mayo Clinic (1). The five most common secondary tumors affecting the
orbit are mucoceles, squamous cell carcinomas, meningiomas, basal cell carcinomas, and
vascular malformations (1). Secondary tumors of the orbit may spread from the paranasal
sinuses, cranium, eyelids, conjunctiva, and the globe itself.
The most common mass lesion of the orbit originating in the paranasal sinuses is the
mucocele. Mucoceles represent 8.3% of all orbital tumors and 18% of all secondary
orbital tumors (1). Mucoceles are likely a result of sinus ostium obstruction leading to an
enlarged fluid-filled sinus that first compresses and then erodes through the bony wall
into the orbit. Mucoceles occur in patients of all ages, with a median age of 51 years old.
Over 80% of mucoceles arise from the frontal or ethmoid sinuses. Most patients present
with a combination of unilateral proptosis, globe displacement away from the mass, lid
swelling, or a palpable superonasal mass. On CT, the mucocele is seen as a well-defined
homogeneous mass extending into the orbit through a bony defect associated with an
opacified sinus cavity. Treatment requires drainage of the obstructed sinus, relief of the
obstruction, and at times sinus obliteration.
Neoplasms of the paranasal sinuses are uncommon. However, the close proximity of the
sinuses to the orbit and eye makes orbital extension common. In a study of 79 patients
with sinus tumors, 45% had evidence of orbital involvement (23). It was also shown that
of the patients with orbital disease, 70% had evidence of orbital extension at the time of
initial presentation. Squamous cell carcinoma was by far the most common sinus tumor
invading the orbit, representing 72% of all sinus tumors reported. Other tumors include
inverting papilloma, adenocarcinoma, and adenoid cystic carcinoma.
The presenting ophthalmic signs and symptoms in patients with sinus tumor extension
include proptosis, facial pain, globe displacement, diplopia, visual loss, epiphora,
conjunctival chemosis, and a palpable orbital mass. These tumors are more common in
men and are almost exclusively seen in older adults. On CT, a homogeneous mass is
noted in the sinus cavity extending into the orbit. Seventy percent to 80% of patients with
sinus tumors have evidence of bony destruction (23). The maxillary sinus is the site of
origin in 80% of cases. Treatment involves complete surgical excision followed by
radiotherapy. Early diagnosis is essential if therapy is to be effective in improving
survival in patients with these tumors.
The most common tumor extending from the cranial vault into the orbit is the
meningioma. In the Mayo Clinic study of orbital tumors, approximately 70% of all
orbital meningiomas were of the secondary type (1). Most of these meningiomas arise
from the sphenoid ridge. Most patients are women with an average age of approximately
50 years old. Secondary orbital meningiomas may present as any slow-growing mass
lesion of the orbit with proptosis, ocular motility disturbances, and decreased visual
acuity. However, two unusual findings are also noted in some cases. One is temporalis
fossa fullness seen in large tumors, and the other is boggy edema of the ipsilateral lower
eyelid. Orbital and neurologic imaging with CT shows the common finding of
hyperostosis of the involved bone. The soft-tissue component may be present in
association with the bony changes. However, MRI with gadolinium enhancement is the
preferred study for evaluating the extent of the tumor. The tumor is hyperintense after
contrast administration. Combined resection by an orbital surgeon and neurosurgeon is
indicated for tumors compromising vision, cranial nerve function, or other vital
intracranial structures.
Basal cell carcinomas, sebaceous cell carcinomas, and squamous cell carcinomas are the
most common eyelid neoplasms. Basal cell carcinoma, the most common eyelid
malignancy, accounts for approximately 90% of all eyelid malignancies (4). They are
most commonly located on the lower eyelid and in the medial canthal area. Sebaceous
cell carcinoma accounts for approximately 4% and squamous cell carcinoma for roughly
5% of all eyelid malignancies. In the Mayo Clinic study, secondary basal cell carcinomas
of the orbit accounted for 2.9% of all orbital tumors (1). The usual treatment for eyelid
basal cell carcinoma is surgical excision using frozen-section margins or Mohs
microsurgery. As might be expected, the patients most at risk for orbital extension are
those who had incomplete excision of the original lesion, received radiotherapy, or
simply neglected the original lesion, allowing it to spread to the orbit. Lesions of the
medial canthal area are also more commonly associated with orbital extension.
Orbital squamous cell carcinoma and sebaceous cell carcinoma arising from the eyelids
are less common than basal cell carcinoma. Henderson (1) at the Mayo Clinic reported 22
(1.6%) cases of secondary orbital squamous cell carcinoma originating in the ocular
adnexa of 1,376 total orbital tumors. The same study reported only four cases of orbital
sebaceous cell carcinoma. The Wills Eye Hospital study of biopsied orbital masses found
similar results (4).
Fixation of the skin tumor to the underlying bone of the orbital rim and ocular motility
disturbances are the most important clues to orbital invasion. CT should be obtained to
investigate the full extent of the orbital process. In cases of proven orbital invasion by
any of these eyelid carcinomas, exenteration followed by radiotherapy is the therapy of
choice.
Squamous cell carcinoma and malignant melanoma are the most common malignant
lesions of the conjunctiva. Although not accounting for a significant number of orbital
tumors, they are known to invade the orbit.
In adults, choroidal melanoma is the most common intraocular tumor to extend into the
orbit. Approximately 8% to 10% of patients with choroidal melanoma have evidence of
extrascleral extension at the time of enucleation (4). In the Mayo Clinic series, orbital
extension or recurrence of uveal melanomas accounted for approximately 2% of all
orbital tumors (1). Recurrence in the orbit may occur from months to many years after the
initial enucleation. Treatment consists of partial or total exenteration, radiotherapy, and at
times chemotherapy. The prognosis is extremely poor, with the 5-year mortality rate as
high as 80%.
Retinoblastoma, a malignant neoplasm of the sensory retina, is the most common
intraocular tumor in children. Orbital extension has been reported in less than 10% of
cases. The most common presentation of recurrent retinoblastoma in the orbit is
displacement and protrusion of the orbital implant placed after enucleation. Recurrent
retinoblastoma in the orbit typically presents within 4 months of the initial enucleation
(4). Treatment of orbital retinoblastoma involves a combination of surgical excision,
radiotherapy, and chemotherapy.
METASTATIC TUMORS
Metastatic tumors are an important cause of orbital disease, representing approximately
8% of all orbital tumors (1). Although most patients with metastatic orbital lesions have a
history of systemic cancer, orbital metastases may signal a reactivation of dormant
disease or the presence of a new systemic malignancy. In 25% of cases, the orbital tumor
is the presenting manifestation of an occult systemic cancer (24). Breast carcinoma is by
far the most common metastatic tumor found in the orbit, accounting for almost 50% of
all metastatic lesions (25). Other tumors known to metastasize to the orbit include lung
carcinoma, prostate, gastrointestinal carcinoma, renal cell carcinoma, thyroid carcinoma,
and malignant melanoma. The most common metastatic tumor in children is
neuroblastoma.
Common presenting findings of metastatic disease of the orbit include upper eyelid
ptosis, proptosis, diplopia, pain, a palpable mass, or vision loss. Interestingly,
enophthalmos is seen in approximately 25% of cases, especially in scirrhous breast and
prostate carcinomas (24). The average age of presentation is approximately 61 years, with
most patients being female. Bilateral eyelid ecchymosis and proptosis are the most
common presenting signs of orbital neuroblastoma.
Multiple patterns of metastases to the orbital structures are seen on CT examination (Fig.
106.10). The most common site of metastasis is the intraconal space, producing a well-
defined infiltrative mass that enhances with intravenous contrast. The bones of the orbit
are another common site of metastatic disease, producing both osteolytic and osteoblastic
lesions. Prostate carcinoma is well known to produce hyperdense osteoblastic bone
lesions. Carcinoma of the breast, gastrointestinal tract, and thyroid have a tendency to
involve both the bone and soft tissues of the orbit. Neuroblastoma frequently causes bony
destruction of the lateral orbital wall. Many of the findings present in metastatic disease
mimic those of other orbital tumors. Biopsy may be required for definitive diagnosis
either via orbitotomy or fine-needle aspiration.

FIGURE 106.10. Computed tomography of metastatic
breast carcinoma of the superior right orbit.



The prognosis for patients with orbital metastases is poor, with an average survival of 10
months. Treatment modalities must be tailored to the specific tumor type and stage of the
systemic disease. In general, radiotherapy is the mainstay of treatment for orbital
metastatic tumors, with chemotherapy and hormonal therapy used in some cases.
CONCLUSION
The scope of disease-producing mass lesions of the orbit is broad. Both children and
adults are affected by orbital tumors. The most common primary orbital tumors are
meningioma, cavernous hemangioma, and lymphoma. Squamous cell carcinoma
represents the most common secondary orbital neoplasm. Breast carcinoma is the most
frequently encountered metastatic tumor of the orbit. Many orbital mass lesions are a
result of various inflammatory conditions, including thyroid-related immune orbitopathy
and idiopathic orbital inflammation. Other common orbital tumors include mucoceles and
dermoid cysts. Rhabdomyosarcoma is the most common malignant tumor in children.
Optic nerve glioma and capillary hemangioma are the most common benign orbital
tumors in children.
The presence of proptosis, as well as its direction and duration, is the most common and
important manifestation of orbital disease. In children, the most common cause of
proptosis is bacterial cellulitis. In adults, the most common cause of unilateral or bilateral
proptosis is thyroid-related immune orbitopathy. Benign tumors typically present with
slowly progressive proptosis over many months to years. Proptosis progressing over a
period of weeks to months typically is seen in malignant tumors and in thyroid disease.
Infections, inflammations, and some malignant tumors present with rapidly progressive
proptosis over a period of days. The history and presenting orbital findings narrow the
diagnosis in most cases. The addition of orbital imaging, most commonly a CT, further
refines the diagnosis. However, because of the diversity of orbital tumors, biopsy is
frequently required for definitive diagnosis. In the case of a child with proptosis and an
orbital mass, emergent biopsy for diagnosis is required to rule out rhabdomyosarcoma or
other malignancy.
Orbital tumors are uncommon, but in some cases patients with orbital disease may
present to an otorhinolaryngologist. In other cases, orbital findings may be discovered in
association with sinus pathology. Early identification and appropriate treatment of these
tumors can protect vision and in some cases prolong life.

HIGHLIGHTS
A myriad of orbital tumors exist arising from every tissue type
in the body.
An orbital tumor must be ruled out in any patient presenting
with proptosis.
Thyroid orbitopathy is the most common cause of bilateral and
unilateral proptosis.
Bilateral orbital tumors are rare, with the only notable
exception being lymphoid lesions.
The most common benign orbital tumor in adults is cavernous
hemangioma. The most common malignant orbital tumor in
adults is lymphoma.
The most common benign orbital tumor in children is dermoid
cyst. The most common malignant orbital tumor is
rhabdomyosarcoma.
Historical clues such as pain, duration of symptoms, tempo of
progression, and associated systemic illness contribute to
developing a differential diagnosis.
Signs of proptosis, nonaxial globe displacement, motility
disturbance, and any associated periocular findings point to the
tumor's location and refine the differential diagnosis.
Imaging is necessary in most cases. CT is the first step in
identifying physical tumor characteristics.
MRI is useful for tumors of the optic nerve and secondary
tumors such as meningioma or sinus carcinoma.
Biopsy will be required in most cases for confirmation of the
diagnosis and treatment of most orbital tumors.
CHAPTER REFERENCES
1. Henderson J. Orbital tumors. New York: Raven Press, 1994.
2. Wilson M, Grossniklaus HE. Orbital disease in North America. Ophthalmol Clin North Am
1996;4:539547.
3. Rootman J. Diseases of the orbit. Philadelphia: J.B. Lippincott, 1988.
4. Shields J. Diagnosis and management of orbital tumors. Philadelphia: W.B. Saunders, 1989.
5. Volpe N, Jakobiec F. Pediatric orbital tumors. Int Ophthalmol Clin 1992;32:201221.
6. Alfred P, Char D. Cavernous hemangioma of the orbit. Orbit 1996;15:5966.
7. Haik B, Jacobiec F, Ellsworth R. Capillary hemangioma of the eyelid and orbit: an analysis of the
clinical features and therapeutic results in 101 cases. Ophthalmology 1979;86:760789.
8. Rootman J, Hay E, Graeb D. Orbital-adnexal lymphangiomas. Ophthalmology 1986;1986:1558
1570.
9. McCormick S, Milite J. Lymphoproliferative disease of the orbit. Ophthalmol Clin North Am
1996;9:693704.
10. Davis J, Parke D, Font R. Granulocytic sarcoma of the orbit. Ophthalmology 1985;92:17581762.
11. Char D, Albin A, Beckstead J. Histiocytic disorders of the orbit. Ann Ophthalmol 1984;16:867
873.
12. Rootman J, Goldberg C, Robertson W. Primary orbital schwannomas. Br J Ophthalmol
1982;66:194204.
13. Wright J, McNabb J, McDonald W. Optic nerve glioma and the management of optic nerve
tumours in the young. Br J Ophthalmol 1989;73:967974.
14. Wright J, McNabb J, McDonald W. Primary optic nerve sheath meningioma. Br J Ophthalmol
1989;73:960966.
15. Wharam M, Beltangady M, Hays D, et al. Localized orbital rhabdomyosarcoma. Ophthalmology
1987;94:251254.
16. Moore A, Buncic J, Munro I. Fibrous dysplasia of the orbit in childhood. Ophthalmology
1985;92:1220.
17. Benedict W, Fung Y, Murphree A. The gene responsible for the development of retinoblastoma
and osteosarcoma. Cancer 1988;62:16911694.
18. Stewart W, Krohel G, Wright J. Lacrimal gland and fossa lesions: an approach to diagnosis and
management. Ophthalmology 1979;86:886895.
19. Bardenstein D. Idiopathic orbital inflammation. Ophthalmol Clin North Am 1996;9:659672.
20. Kennerdell J, Dresner S. The nonspecific orbital inflammatory syndromes. Surv Ophthalmol
1984;29:93103.
21. Sherman R, Rootman J, Lapointe J. Orbital dermoids: clinical presentation and management. Br J
Ophthalmol 1984;68:642652.
22. Lund V, Rolfe M. Ophthalmic considerations in fronto-ethmoidal mucoceles. J Laryngol Otol
1989;103:667669.
23. Johnson L, Krohel G, Yeon E. Sinus tumors invading the orbit. Ophthalmology 1984;91:209217.
24. Goldberg R, Rootman J. Clinical characteristics of metastatic orbital tumors. Ophthalmology
1990;97:620624.
25. Freedman M, Folk J. Metastatic tumors to the eye and orbit. Arch Ophthalmol 1987;105:1215
1219.
Books@Ovid
Copyright 2001 Lippincott Williams & Wilkins
Byron J. Bailey
Head & Neck SurgeryOtolaryngology

107 SALIVARY GLAND NEOPLASMS
Head & Neck SurgeryOtolaryngology
107




SALIVARY GLAND NEOPLASMS
DAVID W. EISELE
MICHAEL E. JOHNS

D.W. Eisele: Department of OtolaryngologyHead and Neck Surgery, Johns Hopkins University School
of Medicine, Baltimore, Maryland.
M.E. Johns: Emory Healthcare, Emory University, Atlanta, Georgia.


Anatomy and Pathology
Benign Neoplasms
Pleomorphic Adenoma
Warthin's Tumor
Oncocytoma
Monomorphic Adenoma
Malignant Neoplasms
Mucoepidermoid Carcinoma
Adenoid Cystic Carcinoma
Acinic Cell Carcinoma
Adenocarcinoma
Polymorphous Low-grade Adenocarcinoma
Carcinoma Ex-Pleomorphic Adenoma
Squamous Cell Carcinoma
Undifferentiated Carcinoma
Sarcoma
Lymphoma
Assessment and Diagnosis
Etiologic Factors
History
Physical Examination
Fine-Needle Aspiration Biopsy
Radiology
Diagnostic Surgery
Staging
Differential Diagnosis
Management
Surgery
Parotidectomy Technique
Surgical Treatment of Parapharyngeal Space Salivary Tumors
Surgical Treatment of Submandibular Gland Neoplasms
Submandibular Gland Excision Technique
Surgical Treatment of Minor Salivary Gland Neoplasms
Radiation Therapy
Chemotherapy
Complications
Parotidectomy
Submandibular Gland Excision
Prognostic Factors
Histopathology
Tumor Size
Facial Nerve Paralysis
Skin Involvement
Regional Lymphatic Metastases
Distant Metastases
Pain
Recurrence
Gender
Location
Acknowledgment
Chapter References
Salivary gland neoplasms are a diverse group of benign and malignant tumors with a
wide range of biologic behaviors. Management requires accurate pathologic diagnosis
because the degree of aggressiveness and patterns of spread of these lesions depend on
their histologic profiles. The surgeon must understand the pathologic behavior of each
tumor type to develop an appropriate treatment plan.
ANATOMY AND PATHOLOGY
The salivary glands are divided into the major salivary glands, which include the paired
parotid, submandibular, and sublingual glands, and the minor salivary glands, which
consist of 600 to 1,000 glands distributed throughout the upper aerodigestive tract.
An accurate histopathologic diagnosis is important for a rational approach to the
management of salivary gland neoplasms. A widely used classification system for
salivary gland neoplasms is that proposed by Batsakis (1) (Table 107.1).

TABLE 107.1. CLASSIFICATION OF EPITHELIAL
SALIVARY GLAND TUMORS



About 80% of salivary gland neoplasms originate in the parotid gland, 10% to 15%
develop in the submandibular glands, and the remaining tumors arise in the sublingual
and minor salivary glands. The smaller the salivary gland, the more likely the salivary
gland neoplasm is malignant. About 80% of parotid neoplasms are benign (Table 107.2),
and about 50% of submandibular tumors are benign (Table 107.3), but fewer than 40% of
the sublingual and minor salivary gland neoplasms are benign (2,3 and 4).

TABLE 107.2. INCIDENCE OF COMMON
PAROTID GLAND NEOPLASMS BY TUMOR
TYPE



TABLE 107.3. INCIDENCE OF SUBMANDIBULAR
GLAND NEOPLASMS BY TUMOR TYPE



Ninety-five percent of salivary gland neoplasms occur in adults. The most common
benign mesenchymal tumor in children is the hemangioma, and the most common benign
epithelial tumor is the pleomorphic adenoma (Table 107.4) (5). The probability of
malignancy in a child is increased if a solid nonvascular salivary mass is found. About
85% of salivary gland malignancies found in children originate in the parotid gland.
Mucoepidermoid carcinoma is the most frequently encountered (50%) tumor type found
in this age group (Table 107.5) (5).

TABLE 107.4. BENIGN SALIVARY GLAND
TUMORS IN CHILDREN



TABLE 107.5. MALIGNANT SALIVARY GLAND
TUMORS IN CHILDREN



BENIGN NEOPLASMS
Pleomorphic Adenoma
The pleomorphic adenoma (benign mixed tumor) accounts for 65% of all salivary gland
neoplasms. These tumors are found most frequently in the parotid gland, followed by the
submandibular gland and the minor salivary glands (Fig. 107.1). Pleomorphic adenoma
also represents the most common tumor for each type of salivary gland. These tumors are
the largest group of epithelial neoplasms in children, and they most commonly develop in
the parotid gland.

FIGURE 107.1. Pleomorphic adenoma of parotid
(arrows) shows a typical location in the tail of the
parotid.



Benign mixed tumor describes the mesenchymal and epithelial components of the tumor.
The gross appearance is smooth and lobular, and it has a well-defined capsule.
Microscopically, there are epithelial and mesenchymal elements (Fig. 107.2; see also
Color Plate 42 following p. 1898). The epithelial component forms a trabecular pattern
within a stroma. The stroma may be myxoid, chondroid, fibroid, or osteoid. The stroma
varies from tumor to tumor and may have a combination of any of these types within a
single tumor. Microscopically, pleomorphic adenomas show incomplete encapsulation
and transcapsular growth with pseudopod extensions. These features account for the high
rate of tumor recurrence after surgical enucleation of these tumors. Adequate surgical
therapy requires resection with an adequate margin of normal gland surrounding the
tumor. Rarely, pleomorphic adenomas can metastasize and yet remain benign
histopathologically.

FIGURE 107.2. Pleomorphic adenoma. The histologic
appearance shows characteristic epithelial and
mesenchymal elements. (See also Color Plate 42
following p. 1898.)



Warthin's Tumor
Warthin's tumor (papillary cystadenoma lymphomatosum), the second most common
benign neoplasm of the parotid gland, accounts for 6% to 10% of all parotid tumors (1).
Although a few cases of Warthin's tumors in submandibular salivary glands have been
reported, this tumor almost always involves the parotid gland. Most cases occur in older
men between the fourth and seventh decades of life, although the incidence appears to be
increasing among women probably related to increased smoking rates in women. The
tumor usually presents as a slowly growing mass in the region of the tail of the parotid
gland. Multicentric Warthin's tumors occur, and approximately 10% of Warthin's tumors
occur bilaterally (6). Malignant Warthin's tumors are rare.
The gross appearance of the tumor is smooth with a well-defined capsule. Cut sections
reveal multiple cystic spaces of different sizes filled with thick mucinous material.
Microscopically, Warthin's tumor has a characteristic appearance with a papillary
epithelium with a lymphoid stroma projecting into cystic spaces (Fig. 107.3). The
epithelium is a double layer of oxyphilic granular cells, with the cells of the inner layer
having the nuclei oriented toward the basement membrane. The cells in the outer layer
have nuclei oriented toward the cystic space.

FIGURE 107.3. Warthin's tumor. Lymphoid stroma and
double-layered epithelium surround the cystic spaces.



Treatment of Warthin's tumor is complete surgical excision. Recurrence after surgical
resection is uncommon.
Oncocytoma
The oncocytoma occurs almost exclusively within the parotid gland and accounts for
fewer than 1% of all salivary gland neoplasms (7). This tumor most commonly occurs in
patients during the sixth decade of life and occurs with equal frequency in men and
women.
The tumors are noncystic, firm, and rubbery. Microscopically, these tumors are
composed of brown, plump, granular eosinophilic cells with small indented nuclei (Fig.
107.4; see also Color Plate 43 following p. 1898). On electron microscopy, mitochondria-
filled cytoplasm is characteristic of oncocytomas.

FIGURE 107.4. Oncocytoma. The histologic appearance
is that of typical plump granular eosinophilic cells. (See
also Color Plate 43 following p. 1898.)



Oncocytomas are commonly found in the superficial lobe of the parotid gland, and
parotidectomy with facial nerve preservation is the treatment of choice. If the tumor is in
a minor salivary gland, excision with a margin of normal tissue is recommended.
Malignant oncocytomas are difficult to differentiate from the benign forms histologically.
Malignant oncocytomas are aggressive tumors with a high rate of regional lymphatic
metastases.
Monomorphic Adenoma
Monomorphic adenomas include basal cell adenoma, clear cell adenoma, glycogen-rich
adenoma, and other rare tumors. The most common monomorphic adenoma is the basal
adenoma, which is commonly found in the minor salivary glands, most often in the upper
lip. The parotid gland is the most frequently involved of the major salivary glands (1).
These tumors are well circumscribed and encapsulated. Microscopically, basal cell
adenomas show rows of peripheral palisading cells with a thick basement membrane.
Basal cell adenomas can be confused with adenoid cystic carcinoma, and it has been
suggested that adenoid cystic carcinoma may represent the malignant counterpart of this
tumor (1).
The monomorphic adenomas are considered benign and nonaggressive neoplasms.
Treatment consists of resection with a margin of normal tissue.
MALIGNANT NEOPLASMS
Mucoepidermoid Carcinoma
Mucoepidermoid carcinoma is the most common malignant tumor involving the parotid
gland and the second most common malignant tumor of the submandibular gland, after
adenoid cystic carcinoma. Between 6% and 9% of all major salivary gland neoplasms are
mucoepidermoid carcinomas (1). Sixty percent to 70% are located in the parotid gland.
The palate is the next most frequent site.
Mucoepidermoid carcinomas are usually classified as low-grade or high-grade tumors.
The low-grade tumors have a higher ratio of mucous cells to epidermoid cells. Low-grade
tumors behave like benign neoplasms but are capable of local invasion and metastasis.
High-grade mucoepidermoid carcinomas have a higher proportion of epidermoid cells
and may resemble squamous cell carcinoma. Special stains for mucin often are required
to differentiate high-grade mucoepidermoid carcinoma from squamous cell carcinoma.
High-grade tumors are aggressive neoplasms with a high propensity for metastasis.
Low-grade mucoepidermoid carcinomas are usually small and partially encapsulated.
High-grade mucoepidermoid carcinomas are usually larger and locally invasive. On cut
section, low-grade tumors may contain mucinous fluid, and high-grade tumors are solid.
Microscopically, low-grade mucoepidermoid carcinoma demonstrates aggregates of
mucoid cells separated by strands of epidermal cells (Fig. 107.5; see also Color Plate 44
following p. 1898). The high-grade tumors have few mucoid elements (Fig. 107.6; see
also Color Plate 45 following p. 1898).

FIGURE 107.5. Low-grade mucoepidermoid carcinoma.
Note the epithelial and glandular elements. (See also
Color Plate 44 following p. 1898.)



FIGURE 107.6. High-grade mucoepidermoid carcinoma.
Note the relative lack of glandular elements. (See also
Color Plate 45 following p. 1898.)



Adenoid Cystic Carcinoma
Adenoid cystic carcinoma (cylindroma) accounts for about 6% of all salivary gland
neoplasms. Adenoid cystic carcinoma occurs less commonly than mucoepidermoid
carcinoma in the parotid gland, but it represents the most common malignancy of the
submandibular gland and the minor salivary glands (1). This tumor accounts for more
than 30% of minor salivary gland tumors, 15% to 30% of submandibular gland tumors,
and 2% to 15% of parotid gland tumors. Adenoid cystic carcinoma occurs with equal
frequency in men and women, usually in the fifth decade of life. This tumor most often
presents as asymptomatic mass. Facial paralysis and pain occur as initial symptoms in
only a small percentage of the cases.
Grossly, adenoid cystic carcinoma is usually monolobular and nonencapsulated or
partially encapsulated. The mass often demonstrates infiltration of surrounding normal
tissue. Microscopically, adenoid cystic carcinoma characteristically has a basaloid
epithelium arranged in cylindric formations in an eosinophilic hyaline stroma (Fig 107.7;
see also Color Plate 46 following p. 1898). Different histologic patterns have been
identified, including cribriform, solid, cylindromatous, and tubular.

FIGURE 107.7. Adenoid cystic carcinoma, showing the
characteristic histologic appearance with eosinophilic
hyaline stroma and perineural invasion. (See also Color
Plate 46 following p. 1898).



Perineural invasion is a typical feature of adenoid cystic carcinoma seen in most cases of
the tumor, which explains the difficulty in tumor eradication despite the extent of surgical
excision. Complete surgical excision and postoperative radiation therapy is recommended
for the management of this tumor. Neutron beam radiation therapy may prove more
effective against adenoid cystic carcinoma than conventional photon radiation therapy
(8). Because adenoid cystic carcinoma may progress in a slow relentless fashion, long-
term follow-up is mandatory for the assessment of therapy results.
Acinic Cell Carcinoma
Acinic cell carcinoma represents 1% of all salivary gland neoplasms and 2% to 4% of
parotid gland neoplasms (1). Ninety percent to 95% of these tumors arise in the parotid
gland, with the remainder found in the submandibular gland. Acinic cell carcinoma of the
minor salivary glands is rare. This distribution corresponds to the fact that these tumors
are composed of the serous cells, which are found predominantly in the parotid gland.
These tumors occur most frequently in patients in the fifth decade of life. Acinic cell
carcinoma occurs most commonly in women. This tumor is the second most common
salivary gland malignancy in childhood after mucoepidermoid carcinoma. Bilateral
involvement occurs about 3% of the time, ranking acinic cell carcinoma second behind
Warthin's tumor for frequency of bilateral parotid gland involvement (1).
Grossly, the well-circumscribed tumors often have a fibrous capsule. There are two
histologic types of cells: those resembling serous acinar cells of the salivary gland and
those with a clear cytoplasm (Fig. 107.8; see also Color Plate 47 following p. 1898).
Tumors occur in several configurations, including cystic, papillary, vacuolated, or
follicular. There is often a lymphoid infiltrate, and cells are characteristically positive on
periodic acidSchiff staining.

FIGURE 107.8. Acinic cell carcinoma. Note cells similar
to serous acinar cells and cells with clear cytoplasm. (See
also Color Plate 47 following p. 1898)



Acinic call carcinoma demonstrates a benign course in early years, but long-term follow-
up studies have shown a decline in survival approaching 50% at 20 years after therapy.
Total parotidectomy with facial nerve preservation, unless the nerve is directly involved
by tumor, is usually sufficient for local control.
Adenocarcinoma
Adenocarcinoma most commonly occurs in the minor salivary glands, followed by the
parotid gland, and represents about 15% of malignant parotid neoplasms (9). These
tumors occur equally in both sexes and usually present as a palpable mass.
Adenocarcinomas arising within the salivary glands are aggressive tumors that are likely
to recur and metastasize.
Grossly, adenocarcinoma is firm or hard and attached to surrounding tissue.
Microscopically, the cylindric cells of variable height form papillae, acini, or solid
masses. Most neoplasms produce mucus, which can be detected by mucicarmine stain.
Adenocarcinoma can be differentiated from mucoepidermoid carcinoma by the lack of
keratin staining. The degree of glandular formation has been used as a means of grading
these tumors.
Polymorphous Low-grade Adenocarcinoma
Polymorphous low-grade adenocarcinoma is the second most common malignancy of the
minor salivary glands (10). This neoplasm most commonly occurs in the palate, buccal
mucosa, and upper lip. Women are affected more commonly than men, and most of these
neoplasms occur in the sixth decade of life. These tumors usually present as a firm
painless mucosalized mass. Tumor growth rates are variable.
Histologically, polymorphous low-grade adenocarcinomas demonstrate variable tumor
cell differentiation and organization. Mitotic figures are unusual, as is necrosis. Tumors
typically have an infiltrative growth pattern with frequent perineural invasion.
Treatment of polymorphous low-grade adenocarcinoma is wide local excision. Prognosis
is generally favorable after complete surgical excision.
Carcinoma Ex-Pleomorphic Adenoma
Carcinoma ex-pleomorphic adenoma (carcinoma ex-mixed tumor) represents a malignant
tumor that has arisen from a preexisting pleomorphic adenoma (Fig. 107.9). The
malignant components and metastases from this malignancy are purely epithelial in
origin. This malignancy represents 2% to 5% of salivary gland tumors.

FIGURE 107.9. Carcinoma ex-pleomorphic adenoma is
seen in a preexisting pleomorphic adenoma.



A true malignant mixed tumor is a rare malignancy that involves both epithelial and
mesenchymal elements. Metastasis from a true malignant mixed tumor contains both
elements.
Clinically, carcinoma ex-pleomorphic adenoma typically presents as a slowly growing
mass, which has usually been present for 10 to 15 years and suddenly increases in size
(1). Malignant transformation of the benign mixed tumor is more likely to occur in long-
standing tumors.
Grossly, the firm tumors are nodular or cystic with minimal encapsulation. The cut tumor
appears similar to a pleomorphic adenoma but reveals necrosis and hemorrhage (1).
Microscopically, a malignant neoplasm arises in a neoplasm that has the characteristics of
a mixed tumor. The malignant portion of the tumor may appear as an adenocarcinoma,
squamous cell carcinoma, undifferentiated carcinoma, or some other form of malignancy
(1).
The diagnosis of carcinoma ex-pleomorphic adenoma may be confusing because the
benign mixed tumor may be mostly replaced by malignant disease, or a tiny focus of
malignant disease may be found within a benign mixed tumor. Destructive infiltrative
growth is a reliable histologic finding for malignancy (1).
Local and distant metastases are common with this tumor, and compared with other
malignant salivary gland neoplasms, it is associated with a very poor prognosis.
Combination surgery and postoperative radiation therapy are recommended. Patients with
pleomorphic adenoma should be encouraged to undergo surgery as soon as possible to
avoid malignant degeneration.
Squamous Cell Carcinoma
Squamous cell carcinoma of the salivary glands represents a rare neoplasm that
constitutes 0.3% to 1.5% of salivary gland tumors (11). Squamous cell carcinoma occurs
more commonly in the submandibular gland than in the parotid gland. Proper diagnosis
of squamous cell carcinoma requires exclusion of contiguous spread of a squamous cell
carcinoma into the gland, metastases to the gland, and high-grade mucoepidermoid
carcinoma.
These tumors usually present as firm indurated masses and occur more commonly in
males, usually in the seventh decade of life. Histologically, these tumors reveal
intracellular keratinization, intercellular bridges, and keratin pearl formation, but they
produce no mucus (1).
There is a high incidence of regional and distant metastases. The prognosis for squamous
cell carcinoma of the salivary gland is poor, and therapy is usually total parotidectomy
with postoperative radiation therapy.
Undifferentiated Carcinoma
Undifferentiated carcinoma is a rare salivary gland malignancy that accounts for about
3% of all tumors of the major salivary glands and 1% to 5% of all parotid malignancies.
These tumors occur equally in men and women, usually in the seventh decade of life (1).
There is a high incidence in Greenlandic Eskimos of undifferentiated salivary carcinomas
thought to be related to the Epstein-Barr virus (12).
These malignancies are primarily small cell histopathologically but are ultrastructurally
heterogeneous and can manifest neuroendocrine differentiation (13). Undifferentiated
carcinomas are extremely aggressive, with marked local invasion and early distant
metastases. These tumors have low survival rates.
Sarcoma
Sarcomas arising in the parotid gland are rare (14). These aggressive malignancies occur
more commonly in men than in women and usually present as an enlarging painless
mass. Rhabdomyosarcomas and fibrosarcomas are the most common histopathologic
types. Diagnosis of a primary sarcoma of the parotid gland requires exclusion of
metastatic spread of a sarcoma to the gland and invasion of the gland by a sarcoma of the
adjacent soft tissues. Primary sarcomas of the salivary glands behave like other soft-
tissues sarcomas, and prognosis correlates with tumor size, sarcoma type, and degree of
histopathologic differentiation (14).
Lymphoma
Primary lymphoma of the salivary glands is rare; the parotid is involved more commonly
than the submandibular gland (15). The criteria necessary for the diagnosis of primary
lymphoma include no known extrasalivary lymphoma, histologic proof that the
lymphoma involves the salivary parenchyma primarily (rather than secondarily from a
lymph node), and architectural and cytologic confirmation of the malignant nature of the
lesion (15).
Primary lymphoma of the parotid gland probably arises within the intraglandular
lymphoid tissue that occurs during embryonic development. The prognosis for salivary
gland lymphomas is generally good.
ASSESSMENT AND DIAGNOSIS
Etiologic Factors
The etiologic factors for salivary gland neoplasms are poorly understood. Tobacco use is
not associated with most salivary neoplasms. Smoking, however, may play a role in the
development of Warthin's tumors. Several studies have implicated low-dose radiation
therapy (16). The parotid gland is the site of the radiation-associated neoplasm in most
reported cases. Radiation-induced salivary gland tumors usually have a latency period of
15 to 20 years. Most radiation-related tumors of the salivary glands are pleomorphic
adenomas. The most common malignant salivary gland tumor after radiation exposure is
mucoepidermoid carcinoma.
Occupational exposure to wood dust in the wood and furniture industries has been linked
to an increased incidence of minor salivary gland neoplasms, particularly
adenocarcinoma of the nasal cavity and paranasal sinuses (17).
History
Patients with salivary gland neoplasms usually present with asymptomatic masses.
Parotid gland neoplasms most commonly occur in the region of the tail of parotid gland
(Fig. 107.1). Benign parotid neoplasms typically enlarge slowly. Pain is unusual with
benign neoplasms, but it can occur if there is associated infection, hemorrhage, or cystic
enlargement. Pain is not a reliable indicator for malignancy. Pain associated with a
malignant tumor is m

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