American Cancer Society

Atlas of
Clinical Oncology

Series Volumes
Blumgart, Fong, Jarnagin Hepatobiliary Cancer
Cameron Pancreatic Cancer
Carroll, Grossfeld, Reese Prostate Cancer
Char Tumors of the Eye and Ocular Adnexa
Clark, Duh, Jahan, Perrier Endocrine Tumors
Droller Urothelial Cancer
Eifel, Levenback Cervical, Vulvar and Vaginal Cancer
Fuller Uterine and Endometrial Cancer
Ginsberg Lung Cancer
Grossbard Malignant Lymphomas
Ozols Ovarian Cancer
Pollock Soft Tissue Sarcomas
Posner, Vokes, Weichselbaum Cancer of the Upper Gastrointestinal Tract
Prados Brain Cancer
Raghavan Germ Cell Tumors
Shah Head and Neck Cancer
Silverman Oral Cancer
Sober, Haluska Skin Cancer
Steele, Richie Kidney Tumors
Volberding Cancer in the Immunocompromised Host
Wiernik Adult Leukemias
Willett Cancer of the Lower Gastrointestinal Tract
Winchester, Winchester Breast Cancer
Yasko Bone Tumors
 American Cancer Society
Atlas of
Clinical Oncology

Editors

GLENN D. STEELE JR, MD

University of Chicago
THEODORE L. PHILLIPS, MD
University of California
BRUCE A. CHABNER, MD
Harvard Medical School

Managing Editor

TED S. GANSLER, MD, MBA

Director of Health Content, American Cancer Society
 American Cancer Society

Atlas of
Clinical Oncology

Pancreatic
Cancer
 American Cancer Society
Atlas of
Clinical Oncology

Pancreatic Cancer
John L. Cameron, MD, FACS
The William Stewart Halsted Professor and Chairman
Department of Surgery
The Johns Hopkins University School of Medicine
Baltimore, MD

2001
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Contributors

ROSS A. ABRAMS, MD BRENNA C. BOUNDS, MD

Clinical Director Gastrointestinal Unit
Department of Radiation Oncology Massachusetts General Hospital
The Johns Hopkins Oncology Center Instructor of Medicine
Baltimore, Maryland Harvard Medical School
Chemotherapy and Radiation Therapy in the Boston, Massachusetts
Adjuvant Management of Pancreatic Cancer Endoscopic Palliation of Pancreatic Cancer

JAMES H. BALCOM IV, MD MICHAEL BOUVET, MD

Resident in Surgery Assistant Professor
Massachusetts General Hospital Department of Surgery
Boston, Massachusetts University of California
Staging of Adenocarcinoma of the Pancreas San Diego, California
Diagnosis of Adenocarcinoma of the Pancreas
HANS G. BEGER, MD, FACS
Professor Surgery MURRAY F. BRENNAN, MD, FACS
Head, Department of General Surgery Chairman, Department of Surgery
University Hospital Ulm Professor of Surgery
Ulm, Germany Memorial Sloan-Kettering Cancer Center
Lymph Node Dissection New York, New York
Management of Adenocarcinoma of the Body
KENNETH F. BINMOELLER, MD and Tail of the Pancreas
Associate Professor
Department of Gastroenterology TARA M. BRESLIN, MD
University of California Assistant Professor of Surgery
San Diego, California University of Wisconsin Medical School
Diagnosis of Adenocarcinoma of the Pancreas Madison, Wisconsin
Neoadjuvant Therapy for Adenocarcinoma of
DIETER BIRK, MD the Pancreas
Department of General Surgery
University of Ulm DAVID L. CARR-LOCKE, MD
Ulm, Germany Directory of Endoscopy
Lymph Node Dissection Brigham and Women’s Hospital
Associate Professor of Medicine
Harvard Medical School
Boston, Massachusetts
Endoscopic Palliation of Pancreatic Cancer

vii
viii CONTRIBUTORS

JEFFREY W. CLARK, MD WAYNE A. FREDERICK, MD

Massachusetts General Hospital
Dana Farber Cancer Institute
Assistant Professor in Medicine
Harvard Medical School
Boston, Massachusetts
Chemoradiation for Unresectable Pancreatic
Cancer
KEVIN C. CONLON, MD, MBA, FACS
Associate Chairman
Department of Surgery
Memorial Sloan-Kettering Cancer Center
New York, New York
Management of Adenocarcinoma of the Body
and Tail of the Pancreas
BRIAN G. CZITO, MD
Resident
Department of Radiation Oncology
Massachusetts General Hospital
Harvard Medical School
Boston, Massachusetts
Chemoradiation for Unresectable Pancreatic
Cancer
DOUGLAS B. EVANS, MD
Professor of Surgery
Department of Surgical Oncology
University of Texas
M. D. Anderson Cancer Center
Houston, Texas
Neoadjuvant Therapy for Adenocarcinoma of
the Pancreas
CARLOS FERNANDEZ-DEL CASTILLO, MD
Associate Professor of Surgery
Harvard Medical School
Associate Visiting Surgeon
Massachusetts General Hospital
Boston, Massachusetts
Staging of Adenocarcinoma of the Pancreas
Chemoradiation for Unresectable Pancreatic
Cancer
Faculty Associate
University of Texas
M. D. Anderson Cancer Center
Houston, Texas
Neoadjuvant Therapy for Adenocarcinoma
of the Pancreas
FRANK GANSAUGE, MD
Department of General Surgery
University of Ulm
Ulm, Germany
Lymph Node Dissection
GEOFFREY R. HOWE, PHD
Gelman Professor of Public Health (Epidemiology)
Division of Epidemiology
Mailman School of Public Health of
Columbia University
New York, New York
Epidemiology of Cancer of the Pancreas
RALPH H. HRUBAN, MD
Departments of Pathology and Oncology
The Johns Hopkins University School of Medicine
Baltimore, Maryland
Molecular Genetics of Adenocarcinoma of the
Pancreas
Familial Pancreatic Cancer
Pathology of Pancreatic Cancer
WILLIAM H. ISACOFF, MD
Division of Medical Oncology
Department of Medicine
UCLA School of Medicine
Los Angeles, California
Chemotherapy and Radiation Therapy in the
Adjuvant Management of Pancreatic Cancer
SCOTT E. KERN, MD
Department of Oncology
The Johns Hopkins University School of Medicine
Baltimore, Maryland
Molecular Genetics of Adenocarcinoma of the
Pancreas
Familial Pancreatic Cancer
 CONTRIBUTORS ix

KEITH D. LILLEMOE, MD MICHAEL G. SARR, MD

Professor and Vice-Chairman Professor of Surgery
Department of Surgery Mayo Medical School
The Johns Hopkins Medical Chair, Division of General and Gastroenterologic
Institutions Surgery
Baltimore, Maryland Mayo Clinic
Surgical Palliation of Pancreatic Cancer Rochester, Minnesota
Palliation of Pain in Adenocarcinoma of the
FABRIZIO MICHELASSI, MD Pancreas
Department of Surgery
The University of Chicago TAYLOR A. SOHN, MD
Chicago, Illinois The Johns Hopkins Medical Institutions
Surgical Management of Adenocarcinoma Baltimore, Maryland
of the Head of the Pancreas via a Radical Surgical Palliation of Pancreatic Cancer
Pancreatectomy
KAREN E. TODD, MD
A. ROBERT MOOSSA, MD UCLA Division of Surgical Oncology
Professor and Chairman UCLA Medical Center
Department of Surgery Los Angeles, California
University of California Prognostic Considerations in Pancreatic Cancer
San Diego, California
Diagnosis of Adenocarcinoma of the Pancreas ANTHONY C. VENBRUX, MD
Assistant Professor of Radiology and Surgery
JOHAN A. OFFERHAUS, MD, PHD Director, Cardiovascular Diagnostic Laboratory
Professor, Department of Pathology The Johns Hopkins Hospital
Academic Medical Center Baltimore, Maryland
University of Amsterdam Pancreatic Carcinoma: Percutaneous Treatment
Amsterdam, Holland
Familial Pancreatic Cancer ANDREW L. WARSHAW, MD
Professor of Surgery
PETER W. T. PISTERS, MD Harvard Medical School
Associate Professor Surgeon-in-Chief
Department of Surgical Oncology Massachusetts General Hospital
University of Texas Boston, Massachusetts
M. D. Anderson Cancer Center Staging of Adenocarcinoma of the Pancreas
Houston, Texas
Neoadjuvant Therapy for Adenocarcinoma of MAURITS J. WIERSEMA, MD
the Pancreas Associate Professor
Mayo Medical School
HOWARD A. REBER, MD Senior Associate Consultant
Department of Surgery Division of Gastroenterology and Hepatology
Chief, Division of Gastrointestinal Surgery Mayo Clinic
UCLA School of Medicine Rochester, Minnesota
Los Angeles, California Palliation of Pain in Adenocarcinoma of the
Prognostic Considerations in Pancreatic Cancer Pancreas
x CONTRIBUTORS

ROBB E. WILENTZ, MD GILBERT WONG, MD

Department of Pathology
The Johns Hopkins University School of Medicine
Baltimore, Maryland
Pathology of Pancreatic Cancer
CHRISTOPHER G. WILLETT, MD
Department of Radiation Oncology
Massachusetts General Hospital
Professor of Radiation Oncology
Harvard Medical School
Boston, Massachusetts
Chemoradiation for Unresectable Pancreatic
Cancer
Assistant Professor of Anesthesiology
Mayo Medical School
Department of Anesthesiology
Division of Pain Medicine
Director of Mayo Clinic Cancer Center
Psychosocial Program
Rochester, Minnesota
Palliation of Pain in Adenocarcinoma of the Pancreas
CHARLES J. YEO, MD
Professor of Surgery and Oncology
The Johns Hopkins University School of Medicine
Attending Surgeon
The Johns Hopkins Hospital
Baltimore, Maryland
Surgical Management: Standard Whipple Procedure
Contents

1 Epidemiology of Cancer of the Pancreas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Geoffrey R. Howe, PhD

2 Molecular Genetics of Adenocarcinoma of the Pancreas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Scott E. Kern, MD, Ralph H. Hruban, MD

3 Familial Pancreatic Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Ralph H. Hruban, MD, G. Johan A. Offerhaus, MD, PhD, Scott E. Kern, MD

4 Pathology of Pancreatic Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Robb E. Wilentz, MD. Ralph H. Hruban, MD

5 Diagnosis of Adenocarcinoma of the Pancreas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

Michael Bouvet, MD, Kenneth F. Binmoeller, MD, A. Robert Moossa, MD

6 Staging of Adenocarcinoma of the Pancreas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

James H. Balcom IV, MD, Carlos Fernandez-del Castillo, MD, Andrew L. Warshaw, MD

7 Surgical Management: Standard Whipple Procedure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

Charles J. Yeo, MD

8 Surgical Management of Adenocarcinoma of the Head of the Pancreas

via a Radical Pancreatectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Fabrizio Michelassi, MD

9 Lymph Node Dissection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

Hans G. Beger, MD, FACS, Frank Gansauge, MD, Dieter Birk, MD

10 Neoadjuvant Therapy for Adenocarcinoma of the Pancreas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

Wayne A.I. Frederick, MD, Tara M. Breslin, MD, Peter W.T. Pisters, MD, Douglas B. Evans, MD

11 Chemotherapy and Radiation Therapy in the Adjuvant Management of Pancreatic Cancer . . . . . 153
Ross A. Abrams, MD, William H. Isacoff, MD
xii CONTENTS

12 Surgical Palliation of Pancreatic Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

Taylor A. Sohn, MD, Keith D. Lillemoe, MD

13 Endoscopic Palliation of Pancreatic Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185

David L. Carr-Locke, MD, Brenna C. Bounds, MD

14 Pancreatic Carcinoma: Percutaneous Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203

Anthony C. Venbrux, MD

15 Chemoradiation for Unresectable Pancreatic Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215

Brian G. Czito, MD, Christopher G. Willett, MD, Jeffrey W. Clark, MD,
Carlos Fernandez-del Castillo, MD

16 Palliation of Pain in Adenocarcinoma of the Pancreas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231

Gilbert Y. Wong, MD, Maurits J. Wiersema, MD, Michael G. Sarr, MD

17 Prognostic Considerations in Pancreatic Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247

Karen E. Todd, MD, Howard A. Reber, MD

18 Management of Adenocarcinoma of the Body and Tail of the Pancreas . . . . . . . . . . . . . . . . . . . . . 255

Kevin C. Conlon, MD, MBA, FACS, Murray F. Brennan, MD, FACS
Preface

Pancreatic cancer is the fifth leading cause of cancer death in the United States. Twenty years ago, there were
virtually no long-term survivors from this dread disease. At the time they were diagnosed, most patients were
inoperable. The few who were operable were mostly unresectable, and of that small group that was resectable,
25 percent died from the operative procedure. The remaining few patients generally died an uncomfortable
and unpleasant death within the next 6 months.
Great strides have been made over the past two decades. Today, there are many new tests to diagnose and
stage pancreatic cancer, the operative procedure of pancreaticoduodenectomy can now be performed with a
very low hospital mortality, adjuvant therapy has proven effective, and more and more patients are surviving
for longer periods of time. In addition, pancreatic cancer used to be among the least studied of the solid
tumors in terms of molecular events leading to the development of the neoplasm. Today, it has become one
of the best studied tumors, and many of the molecular events that accompany the ductal epithelial changes
from normal epithelium to hyperplasia, to dysplasia, to carcinoma in situ and then to invasion are known.
These changes and improvements in the care of patients with pancreatic cancer have evolved in many cen-
ters around the world that have become interested in the management of this disease. Several institutions,
including The Johns Hopkins Hospital, Memorial Sloan-Kettering Cancer Center, M.D. Anderson Cancer Cen-
ter, Massachusetts General Hospital, and UCLA Medical Center in this country, as well as the Universities of
Heidelberg and Ulm in Germany, have been among those institutions that have led the way in stimulating
renewed interest in this disease. A tremendous amount of progress has been made in the past two decades, and
we are perhaps on the threshold of even more exciting advances in the next few years to come. This mono-
graph has brought together many of those who have been the major contributors to the advancements made in
this field over the past 10 years and represents the most current information concerning all aspects of pancre-
atic cancer, from epidemiology through diagnosis and treatment, as well as prognosis and palliation. This
book, with its particularly attractive and illustrative color figures, represents the current state of knowledge
and will inform the reader of all of the most recent advancements that have occurred in this field.

JLC
March 2001

xiii