Speaking Out
Ceruminolytic Agents
Dear Editor:
We were interested in the recent study by
Mansfield PD, et al. (The Effects of Four, Com-
mercial Ceruminolytic Agents on the Middle Ear.
J Am Anim Hosp Assoc 1997;33:479–86.) re-
garding the use of four ceruminolytic agents in
the middle ear. While we applaud the attempt to
debunk dogma regarding the use of otic prepara-
tions, and their risk of ototoxicity, we have sev-
eral concerns regarding the methodology and the
conclusions.
Several studies have been performed with pub-
lished methodologies that have attempted to
simulate the clinical usage of otic preparations
when the tympanic membrane is intact or rup-
tured. Studies of this type provide the most clini-
cal relevance and attempt to answer important
safety questions. 1,2 Unfortunately, the authors’
study did not follow the labeled guidelines re-
garding the recommended use of the products by
the various companies 3 nor does it duplicate the
way these products often are used clinically.
When evaluating agents to make recommenda-
tions regarding clinical safety/use, these issues
need to be addressed.
Two issues preclude the practitioner from in-
corporating the conclusions of this study into
clinical practice. First, the instillation of
ceruminolytics via injection through the tym-
panic membrane (i.e., transtympanic injection)
into the middle ear is not representative of clini-
cal circumstances found in patients with rup-
tured tympanic membranes and clinical otitis
externa/media. Transtympanic administration
should not result in rupture of the tympanic mem-
brane. Results from previous studies demon-
strated that dogs that underwent removal of all
visualized tympanic membrane via electrocau-
tery or curettage had substantial regrowth of the
tympanic membrane in as little as 10 days. 1,2,4 In
two of these studies (which were evaluating gen-
tamicin and chlorhexidine for ototoxicity), my-
ringotomies had to be repeated surgically to
continue to allow complete access to the middle
ear. Given the extensive tissue removal recorded
273
in these studies, it would be difficult to assume
that a 22-gauge needle would result in a perfo-
rated tympanic membrane and hence, a situation
that is clinically similar to natural otitis externa/
media.
The literature indicates that most drugs/agents
can cause damage if deposited directly into the
middle ear. 5 One question we have for the au-
thors is whether otoscopic examinations were
performed throughout the study to evaluate the
tympanic membrane. If they were and the tym-
panic membrane was indeed still ruptured, this
would make the findings more clinically relevant.
It is certainly plausible and not surprising that
the changes reported would occur with these
agents, as there was no drainage of these poten-
tially irritating substances. We assume that the
dog would mount an appropriate inflammatory
response to attempt to confine or remove the
foreign substance. It is unclear if these agents
were actually toxic to the middle ear structures
or if these structures simply were “caught up” in
the inflammatory response and this resulted in
auditory and vestibular damage.
Our second concern is regarding the decision
to inject these products directly into the middle
ear. Three of the four agents are labeled as clean-
ers that need to be flushed well from the ear
canal. 3 Only Adams ™ Pan-Otic is labeled to re-
main in the ear canal. ClearRx™ and Cerumenex ™
are not recommended for usage when the tym-
panic membrane is ruptured.3 The companies pro-
ducing Cerumene ™ and Adams ™ Pan-Otic do not
make recommendations regarding the status of
the tympanic membrane. 3 Consequently, we feel
that this study does not simulate a relevant clini-
cal situation. A prudent practitioner would copi-
ously flush the entire canal with saline or water,
especially if it was later discovered that the tym-
panic membrane was ruptured. 5,6 This study
would have been more informative if these agents
were studied in dogs with experimentally induced
otitis media (i.e., the tympanic membrane com-
pletely destroyed) which would facilitate the
flushing or removal of these products from the
middle ear.
Lastly, of additional concern was the number
of animals sacrificed for this study. It is unclear
what role the guinea pigs should have in a study
that is evaluating agents that are instilled into the
ear canals of dogs when there is much variability
with regard to the potential ototoxicity between
species.6 While we recognize the need to evalu-
ate agents with live animals, sacrificing 24 dogs
for a study that does not follow the labeled indi-
cations of these drugs nor represent the way these
agents are used clinically seems excessive and
inappropriate.
Respectfully,
Kimberly J. Boyanowski, DVM
Terese C. DeManuelle, DVM
Peter J. Ihrke, VMD
University of California Davis,
Davis, California
274
References
1. Strain GM, Merchant SR, Neer TM, Tedford BL. Ototoxicity assessment
of a gentamicin sulfate otic preparation in dogs. Am J Vet Res
1995;56(4):532–8.
2. Merchant SR, Neer TM, Tedford BL, et al. Ototoxicity assessment of a
chlorhexidine otic preparation in dogs. Prog Vet Neurol 1993;
4(3):72–5.
3. Compendium of veterinary products. 4th ed. Distributed by North
American Compendiums, Inc. Port Huron, MI, 1997–1998:123, 297,
318.
4. Steiss JE, Bossinger TR, Wright JC, et al. Healing of experimentally
perforated tympanic membranes demonstrated by electrodiagnostic
testing and histopathology. J Am Anim Hosp Assoc 1992;28:307–10.
5. Walker EM, Fazekas-May MA, Bowen WR. Nephrotoxic and ototoxic
agents. Clinical Lab Med 1990;110:323–54.
6. Merchant SR. Ototoxicity. Vet Clin N Am 1994;24(5):971–9.
 Endogenous Lipid (Cholesterol)
Pneumonia Associated with
Bronchogenic Carcinoma in a Cat
An 11-year-old, female domestic longhair was presented for dyspnea, vomiting, and
left forelimb lameness. A mass in the left caudal lung lobe was seen on thoracic
radiographs. The mass was resected during thoracotomy, and histopathology
confirmed a diagnosis of endogenous lipid pneumonia. The cat recovered slowly
from surgery and was euthanized 11 days following discharge because of persistent
respiratory difficulties. Necropsy findings included lipid pneumonia and bronchogenic
carcinoma, with probable tumor metastasis to the small intestine, spleen, kidney,
and left triceps muscle. J Am Anim Hosp Assoc 1998;34:275–80.

Richard M. Jerram, BVSc, MRCVS Introduction

Cheryl L. Guyer, MS, DVM
Anna Braniecki, DVM
W. Kay Read, DVM, PhD
H. Phil Hobson, DVM,
Diplomate ACVS
C and left forelimb lameness were reported. The referring veterinarian
From the Departments of Small Animal
Medicine and Surgery and Veterinary
Pathobiology,
College of Veterinary Medicine,
Texas A&M University,
College Station, Texas 77843-4474.
Lipid pneumonia is a term used to describe the presence of lipid
substances in the lungs that produce evidence of disease either clini-
cally or radiologically. 1 Synonyms for this condition include choles-
terol pneumonia, lipoid pneumonia, and paraffinoma.
Case Report
A 2.3-kg, 11-year-old, spayed female domestic longhair was referred
to the Texas A&M University Small Animal Clinic for evaluation of
possible megaesophagus and left forelimb lameness. The cat also had
been tachypneic for a period of two weeks. Vomiting/regurgitation
had performed a barium study that had demonstrated a caudal mega-
esophagus. The cat was thin and nonweight-bearing in the left fore-
limb. Body temperature was 99.7˚ F, heart rate was 180 beats per minute,
and respiratory rate was 80 breaths per minute. Heart sounds were
muffled, and breathing appeared labored.
A complete blood count (CBC) was characterized by an increased
white blood cell (WBC) count (43.9 x10 3/µl; reference range, 6 to
17 x10 3/µl). A WBC differential analysis was 92% segmented neutro-
phils, 3% band neutrophils, 2% lymphocytes, 1% monocytes, and 2%
eosinophils. Serum biochemical abnormalities included mild hyper-
glycemia (blood glucose, 133 mg/dl; reference range, 65 to 131 mg/dl);
hypophosphatemia (serum phosphorus, 3.3 mg/dl; reference range,
3.8 to 7.5 mg/dl); hypernatremia (serum sodium, 157 mmol/L; refer-
ence range, 144 to 155 mmol/L); hyperchloremia (serum chloride,
126 mmol/L; reference range, 113 to 123 mmol/L); and a decreased
alanine aminotransferase (15 IU/L; reference range, 26 to 84 IU/L).
Results of the urinalysis were normal. Serological tests for feline
leukemia virus (FeLV) and feline immunodeficiency virus (FIV) were
negative.
Thoracic radiographs were obtained. A well-defined mass was
identified in the caudodorsal portion of the thoracic cavity to the left
of midline [Figure 1]. The heart was displaced from the sternum on
the left lateral radiograph [Figure 2]. A fluoroscopic, liquid barium
esophogram was performed; esophageal flow stopped at the level of

JOURNAL of the American Animal Hospital Association 275

276 JOURNAL of the American Animal Hospital Association
Figure 1—Ventrodorsal thoracic radiograph of an 11-year-old
domestic longhair presented for possible megaesophagus and
left forelimb lameness. The cat was tachypneic. A mass is
evident (arrow) in the left caudal lung lobe (left of the midline).
Figure 2—Lateral thoracic radiograph of an 11-year-old domes-
tic longhair presented for possible megaesophagus and left
forelimb lameness. The mass is seen in the dorsal lung fields
(arrow). The heart is displaced from the sternum.
the mass, then the esophagus distended and contrast
material flowed into the stomach. A neurological ex-
amination showed atrophy of the left shoulder mus-
culature, absence of conscious proprioception in the
July/August 1998, Vol. 34
Figure 3—Photomicrograph of a biopsy section taken from the
mass in the left caudal lung lobe. Alveoli are filled with acicular
cholesterol crystal clefts (arrow), macrophages containing fat
vacuoles of similar size, and a mixture of other inflammatory cell
types including occasional multinucleate giant cells. Inter-
alveolar septae are thickened by fibrous tissue and inflamma-
tory cells and are lined by hyperplastic and hypertrophic type II
pneumocytes (Hematoxylin and eosin stain, 25X; bar=100 µ).
left forelimb, and pain on deep palpation of the left
shoulder. Further preoperative diagnostic work-up
was declined by the cat’s owner, and treatment with
cefazolin a (22 mg/kg body weight, intravenously [IV]
qid) was instituted.
Anesthesia was induced with propofol b and main-
tained with isoflurane.c An exploratory thoracotomy
was performed at the left ninth intercostal space to
evaluate the mass and the caudal esophagus. A dis-
crete, yellow-to-tan, umbilicated, 3 by 2.5 by 1-cm
mass with thickened margins was evident on the me-
dial aspect of the left caudal lung lobe. Adjacent lung
lobes contained multifocal, pinpoint tan lesions. A
left caudal lung lobectomy was performed. The cau-
dal esophagus appeared grossly normal. A chest tubed
was placed during closure, and intermittent thoracic
aspiration was performed for 20 hours postopera-
tively. The left caudal lung lobe was submitted for
histopathology in 10% neutral buffered formalin (NBF).
Thick (5- to 6-mm) slices of fixed tissue from the
mass and adjacent, grossly normal lung parenchyma
were submitted for routine histological processing,
sectioned at 6 µ, and stained with hematoxylin and
eosin (H&E) stain. Alveoli within the well-defined,
nonencapsulated mass contained myriads of aggre-
gates of acicular cholesterol crystal clefts that ranged
from 5- to 15-µ in width and 70- to 150-µ in length
[Figure 3]. The clefts were surrounded by a large
number of epitheloid and foamy cells (presumably
macrophages and hyperplastic type II pneumocytes)
that contained many small, fat vacuoles of similar
size which stained positively with oil red O stain. The
contents of these cells stained lightly or not at all
with periodic acid-Schiff (PAS) stain, indicating that
glycoproteins were not a prominent cellular compo-
July/August 1998, Vol. 34
Figure 4—Photograph of the lungs taken at necropsy. Gross
anatomic alterations of the lungs include a missing left caudal
lung lobe (surgically removed for biopsy) and only two discern-
ible right lung lobes. The right lung lobes are discolored by the
neoplasm, scar tissue, and areas of lipid pneumonia. The 1- to
3-mm in diameter, tan nodules (arrow) scattered throughout the
left cranial lung lobe are areas of endogenous lipid pneumonia
(bar=1 cm) (R=right; L=left).
nent. In addition to this cell population, the alveoli
contained many histiocytic macrophages and fibroblasts.
Neutrophils, lymphocytes, plasma cells, and multi-
nucleate giant cells were less numerous. Interalveolar
septae were thickened by fibrous connective tissue
and a slightly increased number of lymphocytes and
macrophages. Dense populations of lymphocytes and
plasma cells were adjacent to some bronchi that were
lined by hyperplastic, plicated epithelium. Segments
of the epithelium contained an increased number of
goblet cells. Neovascularization in some areas of the
lung was accompanied by a moderate number of mac-
rophages that contained hemosiderin. No evidence of
a tumor or a migrating parasite was found in the
tissue sections examined.
Special stains for bacteria (Gram stain), fungi
(Gomori methanamine silver nitrate stain), acid-fast
bacilli (Kinyoun stain), and partially acid-fast, bacte-
ria-like fungi (Fite stain) were negative. The absence
of extracellular fat globules and glycoprotein within
the mass and the presence of intracellular lipid within
the macrophages indicated the mass was a focus of
endogenous lipid pneumonia rather than exogenous
lipid pneumonia or alveolar proteinosis. None of the
pinpoint tan foci seen at surgery in adjacent lung
lobes were present for evaluation in the left caudal
lung lobe.
On the third day postoperatively, the cat became
severely dyspneic, anorectic, and depressed. Oxygen
(O 2) saturation levels e were 74%; the cat was placed
in an O2 -enriched Kirschner cage, f and O 2 saturation
levels were stabilized at 92% to 96%. A CBC and
serum biochemistry were repeated. Significant find-
ings were an elevated WBC count (23.8 x10 3/µl) with
a differential analysis of 88% segmented neutrophils,
Endogenous Lipid Pneumonia 277
1% band neutrophils, 4% lymphocytes, 5% mono-
cytes, and 2% eosinophils; a decreased blood urea
nitrogen (BUN, 16 mg/dl; reference range, 19 to 33
mg/dl); hypophosphatemia (serum phosphorus, 3.2
mg/dl); and hypochloremia (chloride, 112 mmol/L).
Serum thyroxine (T 4) and triglyceride levels were
within normal limits. Fluid or air in the pleural space
was not detected by thoracic radiography.
The cat improved with O 2 and antibiotic therapy
during the following three days, and at the time of the
owner’s request for discharge, the cat was able to
maintain normal O 2 saturation levels in room air.
Eleven days following discharge, the cat was eutha-
nized by the referring veterinarian due to continued
episodes of severe respiratory distress. A necropsy
was performed at Texas A&M University.
At necropsy, a reduction of the entire body muscle
mass was noted. This change was especially promi-
nent in the muscles of the left forelimb. Gross alter-
ations in the pulmonary architecture included the
absence of the left caudal lung lobe and the presence
of only two distinct right lung lobes [Figure 4]. The
right cranial lung lobe was collapsed, pale red-brown
throughout, and contained numerous, coalescing, pale
tan, soft foci that filled approximately 50% of the
lobe. The second, caudally located lung lobe mea-
sured 4 by 3 by 1.5 cm and was firm and pale tan,
with delicate, white, “lacy” mottling throughout,
which was suggestive of fibrous tissue. The pulmo-
nary parenchyma immediately adjacent to the large,
primary bronchus of the lung lobe was white and
firm. The medial and ventral surfaces of the lobe
were coarsely multinodular, with firm, internodular
adhesions. Two, 7 by 4-mm, smooth, firm plaques of
pulmonary tissue were present ventral to the right
pulmonary hilus.
A single, 5-mm long, 5-mm in diameter, patent,
annular stricture of the jejunal wall was observed 17
cm proximal to the ileocecal junction. A strand of
omental tissue was adhered firmly to the serosa of the
stricture. Three (3- to 14-mm in diameter), smooth,
soft, variegated tan and purple nodules (suggestive of
nodular hyperplasia) raised above the visceral sur-
face of the spleen. Portions of the affected tissues, as
well as representative samples of all major organ
systems, were collected and placed in 10% NBF.
Slices of fixed tissue were processed, sectioned, and
stained with H&E stain as described previously.
Upon microscopic analysis, plaques of tissue at the
right lung hilus and the nodules on the ventral aspect
of the right caudal lung lobe were composed of aggre-
gates of neoplastic epithelial tissue that were accom-
panied frequently by areas of cholesterol pneumonia
[Figure 5]. The tumor cells formed glandular struc-
tures that appeared to arise from the interstitium of
bronchial walls, cross basement membranes, and ex-
278 JOURNAL of the American Animal Hospital Association
Figure 5—Photomicrograph of tissue taken from the right caudal
lung lobe. The area of pulmonary parenchyma is affected by
bronchogenic carcinoma (upper left) and endogenous lipid (i.e.,
cholesterol) pneumonia (upper right, arrow) (Hematoxylin and
eosin stain, 10X; bar=250 µ).
tend into dense, peribronchial fibrous stroma or adja-
cent lung parenchyma. The tumor cells within these
clusters varied in arrangement from single or double
layers of cuboidal cells to sheets in which the cells
piled up and lost polarity. In occasional areas, the
epithelium was pseudostratified, and cytoplasmic
blebs were seen at the apices of cells. The cells re-
acted slightly more strongly with an antibody to high
molecular weight (MW) cytokeratin than to low MW
cytokeratin, suggesting bronchial epithelium as a sec-
ond possible origin of the bronchogenic carcinoma.
The nuclear-to-cytoplasmic ratio of the neoplastic
cells varied markedly. Round-to-oval cell nuclei were
moderately to deeply basophilic and varied somewhat
in size, with occasional giant nuclei present. The nu-
clei usually had one prominent, irregularly shaped
nucleolus. Occasionally, cells in the periphery of
tumor nodules exhibited squamous metaplasia. The
mitotic index was zero to two mitotic figures per
high-power field, and many bizarre, nonmetaphase,
mitotic figures were seen. A few large tertiary bron-
chi, large arterioles, and small arteries nearly were
occluded by scar tissue produced by the neoplasm
[Figure 6]. Within some arterioles, metastatic tumor
cells lined canalizing spaces within the fibrous tissue
thrombi, simulating gland acini.
In the right cranial lung lobe, large areas of lung
parenchyma that were affected by lipid pneumonia
were near small arteries that were plugged partially
by tumor cells. A mild, endogenous lipid pneumonia
was in scattered areas of the subpleural parenchyma
of the left cranial lung lobe. In these areas, a small to
moderate number of macrophages with finely vacu-
olated cytoplasm filled alveoli. The interstitium be-
tween alveoli was thickened by fibrous tissue and an
increased number of macrophages and lymphocytes.
No evidence of a tumor was found in this lobe.
July/August 1998, Vol. 34
Figure 6—Photomicrograph of tissue taken from the right caudal
lung lobe. A large bronchiole is occluded partially by scar tissue
containing acinar clusters of tumor cells. Aggregates of tumor
cells and connective tissue thicken the airway wall. Clusters of
tumor cells infiltrate adjacent lung parenchyma (arrow) (Hema-
toxylin and eosin stain, 10X; bar=250 µ).
Tumor cells within the veins in the pelvis and
medulla of the kidneys slightly invaded the adjacent
stroma. One of the grossly visible, tan nodules in the
spleen (measuring 3 by 3 by 6 mm) was a metastatic
focus of the tumor. At the intestinal stricture, clusters
of glands lined by neoplastic cells were found in the
submucosa and within arterioles in the tunica muscu-
laris. Similar acini of neoplastic cells were within and
adjacent to a small arteriole within the left triceps
muscle. Reduction in the size of myofibers through-
out this muscle bundle suggested that muscle atrophy
was due to interference with the nerve supply to the
muscle. A metastatic tumor compressing the radial
nerve was sought, but none was found in multiple
sections of the muscle examined.
Discussion
Lipid pneumonia can be subdivided depending on the
source of the lipid present. Exogenous lipid pneumo-
nia occurs following aspiration or inhalation of min-
eral, vegetable, or animal oils. Mineral oils do not
elicit a cough reflex but do produce a foreign body
reaction in the pulmonary tissue. 1 Exogenous lipid
pneumonia is an uncommon condition in humans. It
usually is described in elderly humans with a history
of chronic mineral oil use. 1 Diagnosis is made by
sputum examination, lung aspiration, radiography,
computed tomography, and bronchoalveolar lavage
(BAL).1–4 The granulomatous lesions produced may re-
semble a bronchogenic carcinoma on radiographs.1–4
Cytologically, macrophages containing lipid vacuoles
of heterogeneous size and distribution are pathognomic.5
Exogenous lipid pneumonia has been reported in
cattle and cats following forced administration of min-
eral oils. 6–8 Affected cats may present in varying de-
grees of respiratory compromise, although clinical
July/August 1998, Vol. 34
signs usually are mild.9 Animals may be febrile, an-
orectic, and depressed. Diagnosis is based on histori-
cal evidence of mineral oil administration and
radiographs. Lesions seen radiographically may be
misidentified as neoplastic. 9 Histologically, exog-
enous lipid pneumonia is differentiated from endog-
enous lipid pneumonia by the presence of large,
discrete, extracellular globules of lipid in the former
condition. 7
Endogenous lipid pneumonia occurs when pulmo-
nary cell walls break down, causing release of choles-
terol and other lipids into the alveoli. 10 The cause of
this cell wall breakdown is thought to be due to more
proximal airway obstruction, the inhalation of irritat-
ing dust particles, or a disturbance of lipid metabo-
lism.1,7,10,11 In humans, endogenous lipid pneumonia
is common and usually occurs distal to an obstruction
(i.e., neoplasia, chronic abscess, bronchiectasis). 1 The
clinical signs seen are generally the result of the pri-
mary obstructive process. 1 On histological examina-
tion, the affected area contains alveoli filled with
macrophages with foamy cytoplasm. 1,12
Endogenous lipid pneumonia has been reported in
mice, rats, opossums, raccoons, and mongooses.10,11,13
The condition is reported occasionally in cats and
rarely in dogs.7,14 A case of lipid pneumonia has been
reported in a dog; however, in that case an exogenous
source of the lipid could not be ruled out. 14 The dis-
ease appears to occur secondary to bronchial obstruc-
tion, bronchial irritation, long-term inhalant exposure
to dust particles, B vitamin-deficient diets, and hypo-
physectomy. 10 Parasite infestation may be related to
endogenous lipid pneumonia in opossums. 10 The sus-
pected pathogenesis of this form of pneumonia is
related to pulmonary injury which causes prolifera-
tion of alveolar type II cells. This results in overpro-
duction of cholesterol-containing surfactant that
enters the alveoli and is phagocytosed by macro-
phages.10,14 Grossly, the lungs contain subpleural, yel-
lowish-white, firm foci, and the pleura overlying the
lesion often is thickened. 7 Histologically, the alveoli
are distended and filled with foamy macrophages. 1,7,10
Intracellular and extracellular cholesterol crystals, in-
terstitial fibrosis, and hyperplasia of alveolar type II
cells can occur in more severe cases. 1,7
In a small subset of human cases monitored over a
period of months or years, sudden changes in the radio-
graphic appearance and extent of the lesions of indolent
exogenous lipid pneumonia heralded the appearance of
tumors.15 These cases provided strong evidence in sup-
port of the development of neoplasms in lung tissue
altered by lipid pneumonia. This finding has led to the
suspicion that lipid itself, or scar tissue developing in
response to it, may provide a fertile environment for
development of scirrhous tumors. Mineral oil has
been documented as a cause of scrotal cancer in
Endogenous Lipid Pneumonia 279
human workers who were exposed to oily indus-
trial lubricants. 15 It is unknown whether lipid is
capable of causing tumor development in pulmo-
nary tissue.
Immunohistochemistry of the tumor cells and the
glandular morphology and concentration mass at the
hilus of the right lung indicated it was a carcinoma
that originated from bronchial glands or bronchial
epithelium, and suggested it arose at the hilus and
extended peripherally within the right lung. The den-
sity of normal lung tissue at the hilus can make radio-
graphic detection of an early tumor at that site difficult
or impossible. The tumor most likely was present at
the time of the left lung biopsy, since no neoplastic
mass was found in the left caudal lung lobe; but
retrospective immunohistochemistry demonstrated a
rare number of tumor cells intermingled with fat-
laden macrophages within alveoli affected by endog-
enous lipid pneumonia. The cells presumably metastasized
aerogenously to the left caudal lung lobe from the
mass at the right lung hilus. Bronchiolitis obliterans,
caused by scar tissue produced by the tumor, affected
one large tertiary bronchus near the hilus of the right
lung in the tissue sections examined. The endogenous
lipid pneumonia in the peripheral right lung appar-
ently developed secondarily to such bronchial ob-
structions. By a similar mechanism, a microscopically
undetected bronchus or bronchiole obstructed by scar
tissue or tumor cells presumably led to the develop-
ment of the focus of lipid pneumonia in the left cau-
dal lung lobe. In human cases of bronchogenic
carcinoma, pulmonary architecture can be altered to
the point that lung lobes collapse. Extensive involve-
ment of the right lung field by the tumor in this cat
may have caused the loss of distinct middle, caudal,
and accessory lung lobes.
The cat displayed clinical signs of lower respira-
tory tract disease. Failure of clinical signs to resolve
following lung lobectomy can be attributed to sud-
den, rapid growth and spread of the tumor at the
hilus, accompanied by the development of endog-
enous lipid pneumonia. The vomiting could be attrib-
uted to the presence of the metastatic lesions in the
jejunum. The cause of the left forelimb lameness and
muscle atrophy was suspected to be related to me-
tastasis of the tumor to the extensor muscles, although
a mass that directly impinged upon the radial nerve
roots was not found. The cause of the functional
megaesophagus was undetermined.
Both endogenous and exogenous lipid pneumonia
associated with bronchogenic carcinoma have been
reported in humans. To the authors’ knowledge, this
is the first report of endogenous lipid pneumonia as-
sociated with bronchogenic carcinoma in a cat.
(Continued on next page)
280 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

a
Sterile cefazolin sodium USP; Solopak Laboratories, Inc., Elk Grove 7. Dungworth DL. The respiratory system. In: Jubb KVF, Kennedy PC,
Village, IL Palmer NP, eds. Pathology of domestic animals. 3rd ed. Orlando:
b Academic Press, 1985:470–4.
Rapinovet; Mallinkrodt Veterinary, Inc., Mundelein, IL
c 8. Chalifoux A, Morin M, Lemieux R. Lipid pneumonia and severe pulmo-
AErrane; Ohmeda PPD, Inc., Liberty Corner, NJ
d nary emphysema in a Persian cat. Feline Pract 1987;17:6–10.
Trocar catheter; Deknatel, Inc., Fall River, MA
e 9. Hawkins EC. Disorders of the pulmonary parenchyma. In: Nelson RW,
Symphony N-3000; Nellcor, Inc., Pleasanton, CA Couto CG, eds. Essentials of small animal internal medicine. St Louis:
f Mosby-Year Book, 1992:221–2.
Kirschner cage; Kirschner, Inc., Timonium, MD
10. Brown CC. Endogenous lipid pneumonia in opossums from Louisiana.
J Wildlife Dis 1988;24:214–9.

References 11. Hayashi T, Stemmermann GN. Lipid pneumonia in the Hawaiian feral
mongoose. J Path 1972;108:205–10.
1. Wright BA, Jeffrey PH. Lipoid pneumonia. Sem Resp Infect 1990;5: 12. Fisher M, Roggli V, Merten D, Mulvihill D, Spock A. Coexisting
314–21. endogenous lipoid pneumonia, cholesterol granulomas, and pulmonary
2. Lee KS, Muller NL, Hale V, Newell Jr JD, Lynch DA, Im J. Lipoid alveolar proteinosis in a pediatric population: a clinical, radiographic,
pneumonia: CT findings. J Comput Assist Tomogr 1995;19:48–51. and pathologic correlation. Pediatr Path 1992;12:365–83.
3. Brechot JM, Buy JN, Laaban JP, Rochemaure J. Computed tomography 13. Hamir AN, Hanlon CA, Rupprecht CE. Endogenous lipid pneumonia
and magnetic resonance findings in lipoid pneumonia. Thorax (multifocal alveolar histiocytosis) in racoons (Procyon lotor). J Vet
1991;46:738–9. Diagn Invest 1996;8:267–9.
4. Silverman JF, Turner RC, West RL, Dillard TA. Bronchoalveolar lavage 14. Corcoran BM, Martin M, Darke PGG, et al. Lipoid pneumonia in a rough
in the diagnosis of lipoid pneumonia. Diagn Cytopathol 1989;5:3–8. collie dog. J Sm Anim Pract 1992;33:544–8.
5. Kurlandsky LE, Vaandrager V, Davy CL, Stockinger FS. Lipoid pneu- 15. Felson B, Ralaisomay G. Carcinoma of the lung complicating lipoid
monia in association with gastroesophageal reflux. Pediatr Pulmon pneumonia. Am J Roent 1983;141:901–7.
1992;13:184–8.
6. Smith BL, Alley MR, McPherson WB. Lipid pneumonia in a cow.
New Zealand Vet J 1968;16:65–7.
 Cutaneous Mast Cell Tumors in Cats:
32 Cases (1991–1994)
Case records of 32 cats with cutaneous mast cell tumors (CMCTs) were reviewed.
Using the Patnaik system for grading canine mast cell tumors, the relationships
between histopathological grade and patient survival time and tumor recurrence
were examined. Tumor histopathological grade had no prognostic significance.
One-, two-, and three-year tumor recurrence rates following surgical excision were
16%, 19%, and 13%, respectively. Incomplete excision was not associated with a
higher rate of tumor recurrence. J Am Anim Hosp Assoc 1998;34:281–4.

Heather Molander-McCrary, DVM Introduction

Carolyn J. Henry, DVM, MS
Kathleen Potter, DVM, PhD
Jeff W. Tyler, DVM, PhD
Michael S. Buss, DVM, MS
RS
From the Departments of Veterinary
Clinical Sciences (Molander-McCrary)
and Veterinary Microbiology and
Pathology (Potter),
College of Veterinary Medicine,
Washington State University,
Pullman, Washington 99164-6610 and
the Department of Veterinary Medicine
and Surgery (Henry, Tyler, Buss),
College of Veterinary Medicine,
University of Missouri,
379 East Campus Drive,
Columbia, Missouri 65211.
Doctor Molander-McCrary’s current
address is Pets Plus Veterinary Center,
4750 East Grant,
Tuscon, Arizona 85712.
Correspondence should be directed
to Dr. Henry.
The reported incidence of mast cell tumors varies from 2% to 15% of
all tumors in cats. 1–3 Feline mast cell tumors are observed most
commonly on the head, neck, and trunk, but they also may occur in
the visceral organs. 4 Siamese cats are predisposed to the development
of mast cell tumors. 1,4 Canine mast cell tumors are graded histopatho-
logically to permit prediction of patient survival time and prognosis.
In dogs, the most frequently used histopathological grading system
for mast cell tumors was proposed by Patnaik in 1984. 5 In this grad-
ing system, grade I tumors are well differentiated and confined to the
dermis; grade II tumors are moderate to highly cellular with neoplas-
tic cells infiltrating the lower dermal tissue with indistinct cell bor-
ders; and grade III tumors are cellular and pleomorphic with
undifferentiated boundaries and mitotic figures. Using this grading
system, Patnaik, et al. observed an association between mast cell
tumor histopathological grade and survival time in dogs. 5
Although several histopathological grading schemes have been
proposed for use in feline mast cell tumors, none has gained wide-
spread acceptance.2,6,7 Feline mast cell tumors have been classified
generally as well differentiated (i.e., compact), poorly differentiated
(i.e., anaplastic), or histiocytic. 7–9 Well-differentiated tumors are cir-
cumscribed, nonencapsulated masses consisting of solid sheets of
uniform, round cells. 9,10 Poorly differentiated (or anaplastic) mast
cell tumors account for 5% to 10% of mast cell tumors in cats and are
characterized by pleomorphism, increased mitotic activity, and infil-
tration of surrounding tissues. 9,10 Histiocytic mast cell tumors are
small, nonencapsulated, deep dermal or subcutaneous masses often
grouped as papulonodular lesions on the head. 6,9,10 These masses
comprise 10% to 20% of all feline mast cell tumors and are most
common in young (i.e., less than four years of age) Siamese cats. 6,9,10
To the authors’ knowledge, only one prior study with a limited
number (n=14) of cats examined the relationship between histopatho-
logical grade and patient survival time or disease-free interval (DFI).2
This previous study did not examine completeness of surgical exci-
sion as a risk factor for recurrence or survival. The purpose of this
study was to examine a larger independent population of cats with
cutaneous mast cell tumors (CMCTs) in order to determine whether
histopathological grade and completeness of surgical excision are
useful predictors of survival and prognosis.

JOURNAL of the American Animal Hospital Association 281

282 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

Table
Distribution of 32 Feline Cutaneous Mast Cell Tumors (CMCTs)
Within Histopathological Criteria Categories*

Nuclear Pleomorphism Mitotic Rate Extension Beyond Dermis Eosinophils

None (0) 12 25 Absent = 25 9
Category 1 1 2 Present = 7 8
Category 2 16 3 NA† 14
Category 3 3 2 NA 1

* At least 10 fields (400X) were examined for each tumor. Classification criteria were as follows: Nuclear Pleomor-
phism, none seen (0); Category 1 for up to one cell per 400X field; Category 2 for two-to-five cells per 400X field;
Category 3 for more than five cells per 400X field. Mitotic Rate, none seen (0); Category 1 for up to one cell per
400X field; Category 2 for two-to-three cells per 400X field; Category 3 for more than three cells per 400X field.
Extension Beyond Dermis, none (0); present (1). Eosinophils, none (0); Category 1 for one-to-two cells per 400X
field; Category 2 for three-to-five cells per 400X field; Category 3 for more than five cells per 400X field
†
NA=not applicable

Histopathological criteria that were evaluated in-

Figure 1—Grade I feline cutaneous mast cell tumor. The tumor
cells are within the superficial dermis. Cells are uniform in size,
and nuclei are bland. Multinucleated cells and mitotic figures are
absent (Hematoxylin and eosin stain, 80X; bar=36 µ).
Materials and Methods
Archived biopsy samples (from 1991 to 1994) from
cats with CMCTs were obtained for review. Case
inclusion criteria included a histopathological diag-
nosis of CMCT at least one year prior to the begin-
ning of the study, and survival and follow-up more
than one month after the initial diagnosis. The histio-
cytic form of mast cell tumor was excluded, as were
cases with systemic mastocytosis. Practitioners who
had submitted biopsy specimens were contacted by
letter and phone to obtain information regarding tu-
mor location, size, lymph-node involvement, pres-
ence of distant metastasis, treatment type, local
recurrence, date of recurrence, and the cause and date
of death, if applicable. Complete information was
obtained for 32 cases. In each case, the diagnosis of
CMCT was confirmed, and tumors were assigned a
histopathological grade.
cluded nuclear pleomorphism, mitosis, and invasion
of surrounding tissue [see Table]. Eosinophils also
were evaluated but not included in the grading
scheme. At least 10 fields at 400X magnification were
examined to categorize results. Nuclear pleomorphism
was characterized as none (0); one (1) for up to one
cell per 400X field; two (2) for two-to-five cells per
400X field; or three (3) for more than five cells per
400X field. Mitosis was defined as none (0); one (1)
for up to one mitotic figure per 400X field; two (2)
for two-to-three mitotic figures per 400X field; or
three (3) for more than three mitotic figures per 400X
field. Extension of neoplastic cells outside the dermis
was defined as absent (0) or present (1). Eosinophils
were categorized as none (0); one (1) for one-to-two
cells per 400X field; two (2) for three-to-five cells
per 400X field; or three (3) for more than five cells
per 400X field. Histological grades were assigned
based upon the criteria described for canine CMCTs
by Patnaik, et al.5 Briefly, grade I was assigned to
tumors that were small, superficial infiltrates of well-
differentiated mast cells [Figure 1]. Category scores
for nuclear pleomorphism and mitoses were both 0 in
grade I tumors. Grade II was assigned to larger tu-
mors that often extended into the deep dermis [Figure
2]. Anisokaryosis and multinucleated cells were com-
mon, but mitoses usually were rare. Grade II assign-
ment was considered appropriate when nuclear
pleomorphism category scores ranged from 1 to 3,
with a mitosis category score of 0 to 3. Grade III was
assigned to deep dermal or subcutaneous tumors com-
posed of anaplastic cells, which often stained poorly
with toluidine blue [Figure 3]. Category score criteria
for grade III assignment included a nuclear pleomor-
phism score of at least 3 and a mitosis score of at least 1.
July/August 1998, Vol. 34
Figure 2—Grade II feline cutaneous mast cell tumor. Tumor
cells infiltrate the deep dermis. Some nuclear pleomorphism
and numerous binucleate or trinucleate cells are present (He-
matoxylin and eosin stain, 80X; bar=36 µ).
Survival time was defined as the time between
tumor diagnosis and death. Cases that died due to
causes unrelated to CMCT or that were lost to follow-
up were classified as censored. Disease-free interval
was defined as the time from surgical excision to
tumor recurrence or metastasis. Median survival times
and DFIs were compared between older (more than
10 years of age) and younger (less than 10 years of
age) cats, sex groups (male, castrated male, female,
spayed female), breed groups (domestic shorthair,
domestic medium hair, domestic longhair, Siamese,
Himalayan), nuclear pleomorphism grades, mitotic
grades, eosinophilic grades, and histopathological
grades using the Kaplan-Meier method. Group medi-
ans were deemed to differ significantly when p was
less than 0.05. Proportions of cases with tumor recur-
rence, death due to tumor, and death due to any cause
also were reported. The recurrence rates were com-
pared between cases with complete and incomplete
excision using the chi-square test.
Results
The case records of 32 cats had adequate information
available for review and complete responses to ques-
tionnaires by referring veterinarians. Four (12.5%)
cases had more than one lesion at presentation, and
28 (87.5%) cases had single lesions. Of the four cases
with multiple lesions, two had histopathological con-
firmation of CMCTs for all masses and two cases had
only one of the masses submitted for histopathogical
examination. Local lymph-node or distant metastasis
was not detected in any case. Histopathological ex-
amination of excised tissues indicated complete exci-
sion in 10 (31%) of 32 cases and incomplete excision
in 20 (63%) of 32 cases. In two cases, completeness
of surgical margins could not be determined because
all excised tissue was not submitted for examination.
Five cases (complete excision, n=3; incomplete exci-
Mast Cell Tumors 283
Figure 3—Grade III feline cutaneous mast cell tumor. Pleomor-
phic neoplastic cells invade deep cutaneous muscle. Occa-
sional mitotic figures were identified in this tumor (Hematoxylin
and eosin stain, 80X; bar=36 µ).
sion, n=2) had local tumor recurrences. These recur-
rence rates did not differ significantly. Eleven (34%)
of the tumors were grade I, 18 (56%) were grade II,
and three (9%) were grade III. Four cases died due to
causes unrelated to CMCT, and no cases died due to
the tumor. Median survival times and DFI could not
be determined because 28 of 32 cases were alive at
the end of the study and 27 of 32 had no tumor
recurrence.
None of the examined historical risk factors, age,
sex, breed group, histopathological indices listed in
the Table, or tumor grade were associated signifi-
cantly with either survival time or DFI. All cases
were treated with surgical excision only. The ages at
time of diagnosis ranged from one to 18 years. The
mean and median ages at the time of initial diagnosis
were nine and 9.6 years, respectively. The number of
male cases was 12 (all castrated), and the number of
female cases was 20, 15 of which were spayed. The
breeds represented were domestic shorthair (66%),
domestic medium hair (3%), domestic longhair (13%),
Siamese (16%), and Himalayan (3%). Of cases (n=32)
followed for at least one year, five (16%) had tumor
recurrences, none died due to tumor complications,
and four (13%) died due to unrelated causes. Of cases
(n=27) followed for at least two years, five (19%) had
tumor recurrences, none died due to tumor complica-
tions, and three (11%) died due to unrelated causes.
Of cases (n=16) followed for at least three years, two
(13%) had tumor recurrences, none died due to tumor
complications, and two (13%) died due to unrelated
causes.
Discussion
Cutaneous mast cell tumor was not the cause of death
for any case in this study. The cases lived long lives
despite tumor recurrence in 16% of cases. A correla-
tion between histopathological grade and survival
284 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

time could not be established because of the apparent
benign nature of this tumor.
Historically, investigators described feline CMCT
as highly malignant and likely to metastasize to re-
gional lymph nodes and viscera within months. 11 This
belief was challenged by a retrospective study of 14
cases in which a benign behavior was noted, 2 similar
to the findings of the current study. Of 160 cats with
CMCTs in the literature, only four had visceral
metastasis. 6,7,12
2. Buerger RG, Scott DW. Cutaneous mast cell neoplasia in cats: 14 cases
(1975–1985). J Am Vet Med Assoc 1987;190:1440–4.
3. Pulley LT, Stannard AA. Tumors of the skin and soft tissues. In: Moulton
JE, ed. Tumors in domestic animals. 3rd ed. Berkeley: Univ Calif Press,
1990:23–87.
4. Madewell BR, Theilen GH. Mast cell and melanocytic neoplasms. In:
Theilen GH, Madewell BR, eds. Veterinary cancer medicine. 2nd ed.
Philadelphia: Lea & Febiger, 1987:310–5.
5. Patnaik AK, Ehler WJ, MacEwen EG. Canine cutaneous mast cell
tumor: morphologic grading and survival time in 83 dogs. Vet Path
1984;21:469–74.
6. Wilcock BP, Yager JA, Zink MC. The morphology and behavior of
feline cutaneous mastocytomas. Vet Path 1986;23:320–4.

Buerger and Scott reported tumor grades, survival 7. Holzinger EA. Feline cutaneous mastocytomas. Cornell Vet 1973;63:
87–93.
times, and recurrence rates for 14 feline CMCT cases.2 8. Vail DM. Mast cell tumors. In: Withrow SJ, MacEwen EG, eds. Small
Similar to this study, they reported low mortality animal clinical oncology. 2nd ed. Philadelphia: WB Saunders, 1996:
192–210.
figures and a lack of lymph-node involvement. How-
9. Gross TL, Ihrke PJ, Walder EJ. Histiocytic and mast cell tumors. In:
ever, in their study, a greater percentage (36%) of Gross TL, Ihrke PJ, Walder EJ, eds. Veterinary dermatopathology.
cats had recurrent tumors. Although completeness of St. Louis: Mosby-Year Book, 1992:467–73.
surgical excision was not evaluated as a risk factor in 10. Yager JA, Wilcock BP. Round cell tumors. In: Yager JA, Wilcock BP,
eds. Colour atlas and text of surgical pathology of the dog and cat.
Buerger and Scott’s study,2 none of the recurrences London: Mosby-Year Book Europe Limited, 1994:273–86.
they reported occurred at the site of original excision. 11. Scott EW. Feline dermatology 1900–1978: a monograph. J Am Anim
The data in the authors’ study indicates no significant Hosp Assoc 1980;16:331–459.
12. Garner FM, Lingeman CH. Mast cell neoplasms of the domestic cat.
difference in survival time or recurrence rate for cats Pathologia Veterinaria 1970;7:517–30.
with complete versus incomplete surgical excision. In 13. Turrel JM, Kitchell BE, Miller LM, et al. Prognostic factors for radiation
the previously reported study, multiple lesions oc- treatment of mast cell tumor in 85 dogs. J Am Vet Med Assoc
1988;193:936–40.
curred in 64% of cases2 as compared to 13% in the
14. Miller MA, Nelson SL, Turk JR, et al. Cutaneous neoplasia in 340 cats.
present study, and high grades (II or III) occurred in a Vet Path 1991;28:389–95.
proportion of cases (64%) similar to the present study
(66%). The small number of cases with multiple le-
sions is a limitation of this study. In the two cases
with multiple lesions confirmed to be CMCTs, one
had grade I tumors and the other had grade II tumors.
With this small number of cases, it is not possible to
predict the relationship between histopathological
grade and the presence of multiple tumors.
In dogs, recurrence, advanced stage, and high
grades are all factors that decrease survival times. 5,8,13
In this study, recurrence rates at one, two, and three
years were 16%, 19%, and 13% respectively, but
deaths due to tumor did not occur. The sex predilec-
tion of male cats that has been reported previously 2,12
was not noted in this study. This finding correlates
well with Holzinger 7 and Miller, et al. 14 who also
found no sex predilection.

Conclusion
Histopathological grade does not provide useful prog-
nostic information for solitary feline CMCTs. These
tumors should be considered benign and warrant a
good prognosis, provided visceral or systemic disease
is not identified. Incomplete tumor excision was not
associated with decreased survival time or a higher
rate of tumor recurrence.

References
1. Macy DW, MacEwen EG. Mast cell tumors. In: Withrow SJ, MacEwen
EG, eds. Clinical veterinary oncology. Philadelphia: JB Lippincott,
1989:156–66.
 Gastrointestinal Adenocarcinomas
Metastatic to the Testes and
Associated Structures in Three Dogs
Primary testicular neoplasms are common in dogs, but metastases to the testes
are rare. Three dogs had enlargement of the testes and associated structures.
Upon histological examination, the enlargements were due to metastatic
adenocarcinomas. Further examination identified the gastrointestinal tract as the
primary site of the metastatic neoplasms in all three cases. The testicular
metastases reflected widespread metastatic disease. When metastatic
adenocarcinoma is found in the testes and associated structures in dogs, the
gastrointestinal tract should be examined closely for a primary tumor site.
J Am Anim Hosp Assoc 1998;34:287–90.

D. Glen Esplin, DVM, PhD, Introduction

Diplomate ACVP Pathological enlargement of the testes and associated structures can
Sharon R. Wilson, DVM, MS, be caused by inflammation or by primary or secondary testicular
Diplomate ACVP neoplasms. Primary testicular neoplasms are common in dogs, con-
sisting predominantly of seminomas, Sertoli cell tumors, and intersti-
tial (i.e., Leydig) cell tumors. These three neoplasms occur with
C about equal frequency and normally exhibit low rates of metastasis. 1,2
However, metastasis to the spermatic cord and other locations is
reported.1–3 The spermatic cord of a dog with a primary testicular
neoplasm should be examined closely for a metastatic tumor as it
frequently is difficult to determine the malignancy of a testicular
neoplasm by merely examining a section of the tumor.3 Primary
neoplasms of the spermatic cord in domestic animals occur predomi-
nantly in dogs, but they are rare. There are reports of malignant
neoplasms of adipose tissue, fibrous tissue, and striated muscle in the
canine spermatic cord. 3 Secondary neoplasms of the testes in dogs
also are rare. This report documents enlargement of the testes and
associated structures in three dogs, caused by metastasis of adenocar-
cinomas originating in the gastrointestinal tract.

Case Reports

From the Animal Reference
Pathology Division,
Associated Regional and University
Pathologists, Inc. (ARUP Laboratories),
500 Chipeta Way,
Salt Lake City, Utah 84108.
Case No. 1
An 11-year-old, male Yorkshire terrier was presented because of
enlargement of the testes and associated structures. Castration was
recommended. At surgery, the epididymis appeared thickened, so
tissue was collected, fixed in 10% formalin, and submitted for histo-
logical examination.
Upon histological examination, one of the testes and associated
structures contained a neoplastic proliferation of round-to-flattened
epithelial cells with many of the cells forming irregular, variably
sized glands and tubules. Mucus-containing cells, including some
with the morphology of signet-ring cells, were observed within the
neoplastic cell population. Variably sized pockets of extracellular
mucus were intermingled with the neoplastic cells. The cells had

JOURNAL of the American Animal Hospital Association 287

288 JOURNAL of the American Animal Hospital Association
Figure 1—Photomicrograph of biopsy tissue from case no. 1.
Note the neoplastic proliferation of epithelial cells forming ir-
regular, variably sized glands and tubules adjacent to tubules of
the epididymis (arrowheads) and the pockets of extracellular
mucus (arrows) (Hematoxylin and eosin stain, 10X; bar=80 µm).
stimulated a prominent desmoplastic response. The
neoplastic cells had infiltrated extensively the
connective tissue tunics surrounding the testis, epi-
didymis, vas deferens, and spermatic cord. Early in-
filtration into the stroma supporting the epididymis
[Figure 1] and the interstitium of the testis was seen.
As an incidental finding, scattered seminiferous tu-
bules were filled with a proliferation of round cells of
spermatogenic epithelial origin, consistent with an
early intratubular seminoma. The diagnosis of the
epithelial neoplasm was adenocarcinoma. The pa-
thologist suspected the neoplasm had metastasized to
this site and recommended evaluation of the patient
for evidence of a primary tumor site.
Ten days later, an exploratory laparotomy was per-
formed. The surgeon found a large tumor between the
stomach and spleen, which was adherent to both or-
gans. Multiple, thickened areas were seen in the
mesentery. Another large mass was attached to the
ventral abdominal wall in the area of the left inguinal
canal. Tissue was collected, placed in 10% formalin,
and submitted for histological examination. The dog
was euthanized.
Histologically, the mass between the stomach and
spleen contained a neoplastic proliferation of epithe-
lial cells (some of which contained mucus) which had
formed irregular, variably sized glands, tubules, and
some signet-ring cells. Pockets of extracellular mu-
cus were present, and in some areas the pockets had
coalesced, forming lakes. The findings were consis-
tent with a diagnosis of gastric adenocarcinoma. The
mass had a histological appearance very similar to the
neoplasm previously found in the testis and associ-
ated structures, providing evidence that the testicular
neoplasm represented metastasis from the stomach-
associated neoplasm.
July/August 1998, Vol. 34
Figure 2—Photomicrograph of biopsy tissue from case no. 2.
Note the neoplastic glands invading the stroma that is support-
ing the vessels of the pampiniform plexus (arrows) of the
spermatic cord (Hematoxylin and eosin stain, 10X; bar=80 µm).
Case No. 2
An eight-year-old, male, shepherd mixed-breed dog
presented for anorexia and difficulty walking. Physi-
cal examination findings included enlargement of the
testes and spermatic cord as well as a mass on the
right side of the rectum. The mass did not extend into
the perianal area. There was loss of proprioception in
the right rear leg. A biochemical profile and a com-
plete blood count were performed. A slightly low
serum calcium (Ca++ , 8.4 mg/dl; reference range, 8.5
to 11.5 mg/dl) and a mild decrease in the hematocrit
(31.7%; reference range, 36.0% to 52.0%) were noted.
Castration was recommended.
At surgery, the testicular tunics and spermatic cords
of both testes were thickened and were biopsied. In
addition, a biopsy of the rectal mucosa and the associ-
ated mass was collected. All tissues were fixed in 10%
formalin and submitted for histological examination.
Upon histological examination, fibrous tunics of
the left testis were infiltrated extensively by a neo-
plastic proliferation of small, round, epithelial cells
which had formed irregular, variably sized glands
and tubules. Neoplastic glands were in close proxim-
ity to the vas deferens and had invaded into the stroma
supporting the vessels of the pampiniform plexus
[Figure 2]. The fibrous tunics of the right testis and
spermatic cord contained a similar neoplastic cell
population which had infiltrated in a pattern similar
to that seen in the left spermatic cord. The right testis
contained an interstitial (i.e., Leydig) cell tumor sur-
rounded by atrophic seminiferous tubules. The bi-
opsy from the rectum which included both mucosa
and submucosa was normal. Histologically, sections
of the rectal mass were infiltrated extensively by a
neoplastic proliferation of epithelial cells which had
formed irregular glands and tubules having an ap-
pearance similar to the neoplastic glands in the sper-
matic cords and testicular tunics. In one section, the
July/August 1998, Vol. 34
neoplastic glands surrounded bundles of smooth
muscle, indicating the tumor involved the smooth
muscle wall of the rectum. The findings were consis-
tent with a rectal adenocarcinoma metastatic to the
testicular tunics and spermatic cords.
In the weeks following surgery, the dog exhibited
increasing problems with mobility and developed in-
termittent diarrhea. Within two months, the dog was
euthanized.
Case No. 3
A 10-year-old, male cocker spaniel presented after a
groomer reported that the dog was showing signs of
abdominal pain. Upon physical examination, the right
testis was larger than the left testis. Castration was
recommended.
At surgery, both testes and associated structures
were enlarged. A pocket of mucus was associated with
the right testis. Representative tissues from both testes
and associated structures were collected, fixed in 10%
formalin, and submitted for histological examination.
Upon histological examination, the tunics adjacent
to the epididymis and vas deferens from both sides
contained a neoplastic proliferation of epithelial cells.
Neoplastic cells had formed small glands and also
were present as individual cells and small clusters of
cells. The neoplastic cells had elicited a prominent
desmoplastic response. Pockets and lakes of extracel-
lular mucus were present. In one testis, osseous meta-
plasia was seen in the most prominent area of mucous
accumulation. In the same testis, neoplastic epithelial
cells and pockets of extracellular mucus were present
in the fibrous tunic surrounding the testis. The diag-
nosis was adenocarcinoma involving the tunics of the
epididymis, vas deferens, and testes. Metastasis from
the gastrointestinal tract was suspected.
The case was referred to a veterinary surgeon who
performed an exploratory laparotomy. A 20.5-cm (8-
in) segment of small intestine in the area of the junc-
tion of the jejunum and ileum was grossly abnormal
and was resected. The tumor had spread extensively
throughout the falciform ligament and involved the
area of both inguinal canals. Foci of apparent calcifi-
cation were seen in the pancreas. No gross evidence
of hepatic involvement was seen. The intestinal mass
and tissue samples from the falciform ligament were
fixed in 10% formalin and submitted for histological
examination.
Histologically, the intestinal mass contained a pro-
liferation of neoplastic epithelial cells (including sig-
net-ring cells) originating in the intestinal mucosa.
The neoplastic cells had formed irregular, variably
sized glands which had infiltrated extensively into
the submucosa and muscular wall of the organ. Lakes
of extracellular mucus were associated with the infil-
trating tumor cells. In areas, the neoplastic glands
Adenocarcinoma 289
had penetrated the muscular wall completely with
extension into mesenteric adipose tissue. Isolated foci
of neoplastic glands also were seen in the mesentery,
supporting metastatic as well as infiltrating spread of
the neoplasm to this location. Biopsy tissue from the
falciform ligament contained multiple, irregular, vari-
ably sized, and poorly defined foci of anaplastic epi-
thelial cells, some of which had formed small glands.
A marked desmoplastic response was associated with
these metastatic foci. The diagnosis was mucinous
intestinal adenocarcinoma with extension into the
mesentery and metastasis to the falciform ligament.
The dog was euthanized 3.5 months after the ex-
ploratory laparotomy because of anorexia and ab-
dominal pain.
Discussion
In humans, carcinomas metastatic to the testes are
considered rare.4,5 In one series that included over
1,600 testicular neoplasms, only 38 cases of proven
metastatic carcinomas were diagnosed. The main
metastatic neoplasms included bronchogenic and pro-
static carcinomas. 4 Another report indicated that the
prostate gland was the most frequent primary site for
carcinomas metastatic to the testes. 5 Carcinomas
metastatic to the testes appear to be even more rare in
domestic animals, 3 but they have been reported in
dogs. 6,7 This rarity may be due to the relatively low
incidence of prostatic carcinomas in animals, but fail-
ure to examine testicular tissue carefully in cases of
carcinomas of other organs also is likely a factor.
Although case nos. 1 and 2 had primary testicular
neoplasms, the glandular carcinomas which had infil-
trated the testes and associated structures of both
cases showed no resemblance to primary testicular
neoplasms, indicating metastasis of the carcinomas
from a distant, nontesticular, primary site. Gland and
tubule formation, signet-ring cells, and lakes of
extracellular mucus are features found in gastrointes-
tinal adenocarcinomas. 6–9 These features in the
neoplasm from case no. 1 and the tumor’s close asso-
ciation with the stomach support a gastric origin for
this neoplasm. In case no. 2, origin of the pararectal
neoplasm from the glands of the anal sac has to be
considered. Adenocarcinomas of the glands of the
anal sac are very aggressive and are known to infil-
trate into the pelvic cavity.10 No tumor mass was
detected in the perianal area on presurgical physical
examination, but anal sac gland adenocarcinomas of-
ten are occult, lying in subcutaneous tissue adjacent
to the anus and covered by freely movable, haired
skin. 11 However, in one study, over 90% of the dogs
with adenocarcinomas of the glands of the anal sac
also had hypercalcemia, and over 90% of the tumors
occurred in female dogs.11 The glands of the anal sac
as the origin of the pararectal neoplasm in case no. 2
290 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

seem unlikely since the dog was a male with a slightly 6.
low serum Ca ++. Even though the point of origin of 7.
the neoplasm was not visualized histologically, ori-
gin from the rectal mucosa seems likely, as the glan- 8.
dular tumor was associated closely with the rectum
9.
and involved the smooth muscle wall of the organ. In
case no. 3, histological examination confirmed the 10.
origin of the adenocarcinoma to be from the mucosa
of the small intestine. 11.
When a testicular carcinoma is secondary in
humans, it usually is found incidentally at autopsy of
Patnaik AK, Hurvitz AI, Johnson GF. Canine intestinal adenocarcinoma
and carcinoid. Vet Path 1980;17:149–63.
Patnaik AK, Hurvitz AI, Johnson GF. Canine gastric adenocarcinoma.
Vet Path 1978;15:600–7.
Head KW. Tumours of the lower alimentary tract. Bull Wld Hlth Org
1976;53:167–86.
Head KW. Tumors of the alimentary tract. In: Moulton JE, ed. Tumors
in domestic animals. 3rd ed. Berkeley: Univ Calif Press, 1990:347–435.
Pulley LT, Stannard AA. Tumors of the skin and soft tissues. In: Moulton
JE, ed. Tumors in domestic animals. 3rd ed. Berkeley: Univ Calif Press,
1990:23–87.
Meuten DJ, Cooper BJ, Capen CC, et al. Hypercalcemia associated with
an adenocarcinoma derived from the apocrine glands of the anal sac.
Vet Path 1981;18:454–71.

a patient with widespread metastatic disease, or at

orchiectomy for prostatic carcinoma.4 In dogs, intes-
tinal adenocarcinomas and especially gastric adeno-
carcinomas can be widely metastatic.6,7 At laparotomy,
the gastric adenocarcinoma in case no. 1 and the
intestinal adenocarcinoma in case no. 3 showed evi-
dence of widespread abdominal metastasis. The tes-
ticular metastasis appears to be a reflection of the
widespread metastatic disease in these two cases. Nei-
ther a laparotomy nor a postmortem examination was
performed for case no. 2.

Conclusion
The three cases in this report demonstrate the impor-
tance of histologically examining the testes and asso-
ciated structures in all dogs with testicular masses to
determine if a primary testicular neoplasm is present,
to check for evidence of metastasis of a primary tes-
ticular neoplasm, and to rule out metastasis from a
distant, nontesticular, primary neoplasm. Secondary
carcinomas of the testes seem to indicate widespread
metastatic disease. In all three cases of this report and
in two previous reports of metastasis to the testes, 6,7
the primary neoplasms were in the gastrointestinal tracts.
These findings would suggest that when metastatic
adenocarcinoma is found in the testes and associated
structures of a dog, close examination of the gastrointes-
tinal tract for a primary tumor site is indicated.

Acknowledgments
The authors thank Drs. D. S. Halpern, A. Grossman,
S. W. Cho, A. J. Schulman, and E. J. Walder for submit-
ting the cases and providing follow-up information.

References
1. Nielsen SW, Lein DH. Tumours of the testis. Bull Wld Hlth Org
1974;50:71–8.
2. Nielsen SW, Kennedy PC. Tumors of the genital systems. In: Moulton
JE, ed. Tumors in domestic animals. 3rd ed. Berkeley: Univ Calif Press,
1990:479–517.
3. McEntee K. Scrotum, spermatic cord, and testis: proliferative lesions.
Reproductive pathology of domestic animals. San Diego: Academic
Press, 1990:279–306.
4. Price EB Jr, Mostofi FK. Secondary carcinoma of the testis. Cancer
1957;10:592–5.
5. Meares EM Jr, Ho TL. Metastatic carcinomas involving the testis: a
review. J Urol 1973;109:653–5.
 Infantile Desmoid-Type Fibromatosis
in an Akita Puppy
A 10-week-old Akita puppy was evaluated for a reported umbilical hernia. Repair of
the hernia had been attempted three times prior to referral. A defect in the ventral
abdominal wall with an associated soft-tissue mass was identified on abdominal
radiographs. Exploratory surgery was performed; the mass was resected and the
abdominal wall defect was repaired. Histopathological evaluation of the mass was
consistent with infantile desmoid-type fibromatosis.
J Am Anim Hosp Assoc 1998;34:291–4.

James L. Cook, DVM Introduction

James R. Turk, DVM, PhD,
Diplomate ACVP
Eric R. Pope, DVM, MS,
Diplomate ACVS
Robert C. Jordan, DVM
C edge, IDTF has not been reported in the veterinary literature.
Congenital, infantile, and juvenile neoplasms occur rarely in dogs.
Neoplasms reported to occur most frequently in young dogs include
histiocytoma, papilloma, lymphoma, osteosarcoma, and fibrosar-
coma. 1 Infantile desmoid-type fibromatosis (IDTF) has been reported
to occur in children from birth to five years of age. 2–5 This tumor or
tumor-like lesion usually occurs as a solitary mass arising from skel-
etal muscle, fascia, aponeuroses, or periosteum.2 Histopathologically,
IDTF varies in its appearance, from primitive mesenchymal forms to
tumors that closely resemble adult desmoids. 2–4 To the authors’ knowl-

From the Departments of Small Animal
Medicine and Surgery (Cook, Pope,
Jordan) and Pathobiology (Turk),
Veterinary Medical Teaching Hospital,
College of Veterinary Medicine,
University of Missouri,
379 East Campus Drive,
Columbia, Missouri 65211.
Case Report
A 10-week-old, male Akita was presented to the University of Mis-
souri-Columbia Veterinary Medical Teaching Hospital (UMC-VMTH)
for evaluation of a reported recurrent umbilical hernia. Prior to ad-
mission, surgical repair of the hernia had been attempted three times
without success. The puppy was presented to the UMC-VMTH for
definitive surgical correction.
Upon physical examination, the puppy was alert, responsive, and
in good body condition. The puppy’s rectal temperature was 38.1˚ C,
pulse rate was 144 beats per minute, and respiratory rate was 30
breaths per minute. The most significant physical examination find-
ing was the presence of a palpable mass within the subcutaneous
tissues of the midventral abdominal wall. The mass extended from the
xiphoid cartilage to midway between the umbilicus and prepuce and
from 2-cm left to 6-cm right of midline. A palpable defect in the linea
alba was present deep to the mass at the area of the umbilicus. A
portion of the mass could be reduced within the abdominal cavity by
digital manipulation. An ulceration approximately 2.5 cm in diameter
was present in the skin immediately lateral to the umbilicus on the
left side.
A soft-tissue mass associated with the ventral abdominal wall was
identified on abdominal radiographs [Figure 1]. A radiographically
visible defect in the abdominal wall also was noted. A radiolucent,
tubular structure consistent with an intestinal loop was located out-
side of the abdominal cavity. The radiographs were considered to be
consistent with umbilical herniation and an abdominal wall mass.

JOURNAL of the American Animal Hospital Association 291

292 JOURNAL of the American Animal Hospital Association
Figure 1—Lateral radiographic view of the abdomen of an Akita
puppy demonstrating a soft-tissue mass associated with the
ventral abdominal wall and a defect in the midventral abdominal
musculature.
Figure 2—Photomicrograph of a section of the tumor demon-
strating epithelioid and spindle-cell infiltration of adipose tissue
and skeletal muscle (Hematoxylin and eosin stain, 400X; bar=
50 µ).
Packed cell volume, plasma total protein, and se-
rum urea nitrogen levels were within normal limits.
An abdominal wrap was placed, and the puppy was
monitored for deterioration in clinical status prior to
surgery. The differential diagnoses considered in-
cluded umbilical herniation alone or in combination
with granuloma, inflammation, fibrosis, or neoplasia.
Upon surgical exploration of the area, a subcutane-
ous mass was associated with the external rectal
sheath and it extended into the abdominal wall defect.
Herniated tissue at the time of surgery consisted only
of a small amount of omentum. The mass was located
predominantly to the right of midline. Surgical resec-
tion of the mass including overlying skin, all associ-
ated muscle, fascia, and cartilage (including a portion
of the xiphoid cartilage and the distal 2-to-3 cm of the
July/August 1998, Vol. 34
Figure 3—Photomicrograph of a section of the tumor demon-
strating neoplastic cells stained faintly positive for Masson’s
trichrome surrounded by reticulin fibers (Masson’s trichrome
stain, 400X; bar=50 µ).
11th through 13th ribs on the right) was accomplished
by sharp dissection. All grossly abnormal tissue was
removed and submitted for culture and histopatho-
logical evaluation. Omental adhesions to the affected
area were divided sharply. Adhesions of the small
intestine to the previous incision site were divided
sharply. The intestines did not appear to be affected
grossly. During the course of resection, a 1-cm com-
munication with the thoracic cavity was created. The
patient was ventilated appropriately until the defect
was closed and a negative pleural pressure was rees-
tablished. The abdominal musculature was reapposed
with the creation of only minimal tension. Subcutane-
ous tissue and skin closure was routine. The patient
recovered without incident and was discharged the
following day.
The resected tissue varied in morphology when
examined histopathologically. One section was com-
posed of haired skin containing a poorly defined,
nodular proliferation of vacuolated, epithelioid-to-
spindle cells with generally indistinct nucleoli and no
mitotic figures. Numerous small blood vessels coursed
through the nodules. The cells extended into the sub-
jacent panniculus and skeletal muscle. Another sec-
tion was composed of similar epithelioid-to-spindle
cells infiltrating adipose tissue and skeletal muscle
[Figure 2]. Another section demonstrated similar cells
incarcerating portions of costal cartilage. Masson’s
trichrome, Gomori’s reticulum, and Alcian blue-peri-
odic acid-Schiff stains at pH of 2.5 and 1 were per-
formed on sections of the mass. The spindloid
mononuclear cells were faintly Masson’s-trichrome
positive and Alcianophilic at pH of 2.6 and were
surrounded by reticulin fibers [Figure 3]. Histopatho-
logical findings were consistent with a diagnosis of
IDTF.
The puppy was examined 17 days postoperatively,
at which time skin staples were removed. No compli-
July/August 1998, Vol. 34
cations or evidence of recurrence were reported. No
abnormalities were found by complete physical ex-
amination. During telephone conversations 14 months
after surgery, the dog was reported by the owner and
referring veterinarian to have had no evidence of com-
plications or recurrence related to the surgery.
Discussion
Infantile desmoid-type fibromatosis is a tumor or tu-
mor-like lesion in children that has not, as yet, been
reported in the veterinary literature. This neoplasm in
children usually presents as a firm, solitary mass that
is circumscribed poorly, deeply seated, and rapidly
growing. It is encountered most commonly in the first
two years of life. The most frequent sites of occur-
rence are the skeletal muscles of the head and neck,
the shoulder and brachium, and the thigh.2 Infantile
desmoid-type fibromatosis lesions involving the ab-
dominal musculature have been reported.3,4 In chil-
dren, males are affected slightly more often than
females. 2
Infantile desmoid-type fibromatosis lesions may
progress to incorporate and infiltrate vessels, nerves,
and muscle. The tumor also may involve joints, bone,
and any other structures present, resulting in tender-
ness, pain, and dysfunction. Radiology usually
demonstrates a soft-tissue mass with or without in-
volvement of associated structures. 2–5
Grossly, the neoplasm consists of a firm, poorly
defined, fibrous mass of gray-white tissue. Encapsu-
lation does not occur. The tumor usually is adhered to
the involved muscle and subcutaneous tissue. 2,4,5
Histopathologically, several patterns can be distin-
guished that reflect sequential stages of fibroblast
maturation. The immature form is the most common
type and generally is found in infants during the first
few months of life. This form is characterized by a
haphazard arrangement of small cells associated with
a dense reticulin fiber meshwork and mucoid mate-
rial. The appearance of the cells is consistent with a
stage between primitive mesenchymal cells and fi-
broblasts. The cells infiltrate muscle diffusely and
can be associated with lymphoid cells. 2
The second form of IDTF is characterized by more
mature-appearing, spindle-shaped fibroblasts ar-
ranged in distinct bundles. Collagen production is
seen with this type of tumor. This form of the neo-
plasm generally is considered to be more aggressive
and may be difficult to distinguish from infantile
fibrosarcoma. The cellularity of this tumor may vary,
and osseous metaplasia has been reported. 2,5
The differential diagnoses for IDTF in children
include myxoid liposarcoma, botryoid rhabdomyo-
sarcoma, lipoblastomatosis, fibrodysplasia ossificans
progressiva, fibrous hamartoma, and fibrosarcoma.
Distinction of IDTF from other infantile neoplasms is
Fibromatosis 293
based primarily on the overall diffuse growth pattern
of IDTF and its tendency to contain residual muscle
and fat with an alternating pattern of cellular and
collagenous areas. Infantile neoplasms displaying a
high degree of cellularity with a high mitotic index
that grow in an expansile, destructive manner are
more indicative of fibrosarcoma. 2–5 Further differen-
tiation based on electron microscopy or immunohis-
tochemistry is unnecessary for definitive diagnosis
and has not been described in the human or veterinary
literature to the authors’ knowledge.
Complete surgical excision is the treatment of
choice.2,4,5 However, resection may be inhibited by
anatomical location and associated structures. Re-
sponse of IDTF to radiation therapy has not been
reported in the medical literature.
Infantile desmoid-type fibromatosis lesions appar-
ently do not metastasize. However, incomplete surgi-
cal resection may result in local recurrence. Neither
location nor histological appearance appear to be good
prognostic indicators of disease course. Although no
definitive etiology has been determined, trauma often
is implicated. No hereditary role has been suggested.2,4,5
The clinical and histopathological findings in this
case were consistent with the immature form of IDTF.
Certainly, the tissue trauma associated with umbilical
herniation could be implicated as a precipitating cause
for this neoplasm. It could not be ascertained as to
whether the original mass palpated by the referring
veterinarian was herniated tissue or an early IDTF
lesion. An idiopathic etiology also is plausible. Sur-
gical excision was performed as sole treatment in this
case and appears to have been curative. Preoperative
biopsy would have confirmed the presence of neopla-
sia but would not have altered the surgical plan. Wide
surgical excision including adjacent normal tissue was
performed. Since the mass extended through the ab-
dominal wall in some areas, seeding of the abdominal
cavity contents is a potential sequela. Regular follow-
up examinations and careful observation for any signs
of recurrence are recommended.
Conclusion
The present case describes the first reported case of
IDTF in the veterinary literature. It is important for
the veterinary clinician to be aware of infantile neo-
plasms when diagnosing and treating masses in young
patients.
References
1. Dorn CR, Priester WA. Epidemiology. In: Theilen GH, Madewell BR,
eds. Veterinary cancer medicine. 2nd ed. Philadelphia: Lea & Febiger,
1987:39–42.
2. Enzinger FM, Weiss SW. Soft tissue tumors. St. Louis: C.V. Mosby,
1988:164–200.
(Continued on next page)
References (cont’d)
3. Allen PW. The fibromatoses: a clinicopatho-
logic classification based on 140 cases. Am J
Surg Path 1977;1:305–21.
4. Booher RJ, Pack GT. Desmomas of the abdomi-
nal wall in children. Cancer 1951;4:1052–65.
5. Fromowitz FB, Hurst LC, Nathan J, et al. Infan-
tile (desmoid type) fibromatosis with extensive
ossification. Am J Surg Path 1987;11:
66–75.
 Malignant Mesenchymoma Associated
with an Unusual Vasoinvasive Metastasis
in a Dog
A case of a malignant mesenchymoma with an unusual, vasoinvasive, metastatic
behavior in a three-year-old, intact female basset hound is presented. Malignant
mesenchymomas are rare neoplasms in humans and in dogs. No previous reports
of a malignant mesenchymoma with vasoinvasive metastasis in the dog were found
in the literature. The constituent neoplasms are discussed in relation to reports in
the human and veterinary literature, and a potential etiology for this unique
presentation is hypothesized. J Am Anim Hosp Assoc 1998;34:295–9.

Timothy M. Robinson, DVM Introduction

Richard R. Dubielzig, DVM, PhD Mesenchymal neoplasms are those tumors arising from connective
tissue, skeletal tissue, blood vessels, and lymphatics. 1 A malignant
Jonathan F. McAnulty, DVM, PhD mesenchymoma is a neoplasm of mesenchymal origin composed of
tumor cells differentiating into two or more unrelated malignant
forms.2 Mesenchymomas are extremely rare neoplasms in dogs.3 In
C addition, intravascular neoplasms generally are rare in dogs. To the
authors’ knowledge, this is the first reported case of a malignant
mesenchymoma of liposarcomatous and osteosarcomatous origin with
vasoinvasive metastasis in the dog.

From the Departments of Surgical
Sciences (Robinson, McAnulty) and
Pathobiological Sciences (Dubielzig),
School of Veterinary Medicine,
University of Wisconsin,
Madison, Wisconsin 53706.
Case Report
A 19.4-kg, three-year-old, intact female basset hound was referred to
the University of Wisconsin Veterinary Medical Teaching Hospital
(UWVMTH) with a diagnosis of an abdominal mass. One week prior
to presentation, the dog had become lethargic, inappetent, and had
vomited bile occasionally. The referring veterinarian performed an
exploratory celiotomy and found a large, cyst-like, intra-abdominal
mass solidly adhered to the dorsal aspect of the abdomen. The dog
was recovered from anesthesia without further dissection of the mass,
and she was referred.
On physical examination, the dog was alert, responsive, and mildly
febrile (103.6˚ F). Clinical laboratory parameters were within normal
limits except for a mature neutrophilic leukocytosis. No evidence of
metastasis was seen on thoracic radiographs. A large, circumscribed,
soft-tissue opacity displacing intestinal loops ventrally was seen on
abdominal radiographs. A 15 by 10 by 8-cm, lamelliform mass of
mixed echogenicity, which was confluent with the caudal right kid-
ney, was identified by abdominal ultrasonography. The mass ex-
tended caudally to the area of the bladder and medially ventral to the
aorta to the caudal pole of the left kidney. No evidence of splenic or
hepatic metastasis was noted. Ventral and abaxial displacement of the
ureters with no evidence of obstruction was discovered by an excre-
tory urogram. Differential diagnoses included intra-abdominal or ret-
roperitoneal abscess; intravascular thrombosis; neoplasia of renal,
ovarian, splenic, adrenal, lymphatic, or intravascular origin; teratoma;
nephroblastoma; and fungal or parasitic disease.

JOURNAL of the American Animal Hospital Association 295

296 JOURNAL of the American Animal Hospital Association
Figure 1—Intraoperative photograph of the caudal abdominal
cavity. Note the confluence of the common iliac veins into the
caudal vena cava (small arrow) which entered the caudal aspect
of the mass (large arrows).
An exploratory laparotomy was performed, and a
large, cyst-like mass with a smooth wall was found
extending from the left kidney to the right kidney and
caudally to the bifurcation of the vena cava. The
kidneys were of normal size and shape. The caudal
vena cava entered the caudal aspect of the mass [Fig-
ure 1]. Cranial to the mass, the vena cava was very
small. Multiple, dilated veins terminated in the wall
of the mass. The mass was removed by meticulous
blunt and sharp dissection. After the mass was
resected, it was determined that approximately 10 cm
of the caudal vena cava was incorporated into the
mass. The dog recovered uneventfully from surgery.
On cut section, the mass was granular in appear-
ance, orange-to-brown, and exhibited a lamelliform,
multilayered structure on longitudinal section [Figure
2]. Anaerobic, aerobic, and fungal cultures were sub-
mitted. A nonhemolytic Staphylococcus was isolated
on the aerobic culture and it was sensitive to penicil-
lins and probably represented contamination from an-
other source. The primary differential diagnoses at
this time remained intravascular thrombosis, abscess
of fungal or bacterial origin, vasculitis, or neoplasia
of vascular origin.
Since the caudal vena cava was removed from just
proximal to its caudal bifurcation to the porta hepatis,
a femoral venogram was performed using digital sub-
traction imaging to determine the route of venous
drainage from the caudal veins to the central circula-
tion. The contrast media flowed proximally from the
femoral vein into the external iliac vein and common
iliac vein where the contrast media could be seen in
multiple, arborizing venous branches extending cra-
nially and caudally from the external iliac and com-
mon iliac veins. The greatest amount of venous flow
appeared to be through the caudal superficial epigas-
tric veins and the median sacral veins, presumably
July/August 1998, Vol. 34
Figure 2—Photograph of the mass after surgical removal from
the abdomen. Note the lamellated appearance of the interior
following incision (arrow).
reaching the cranial central circulation via the verte-
bral veins. After recovery, the dog was discharged.
Amoxicillin-clavulanic acid (22 mg/kg body weight,
per os [PO] bid for seven days) was to be given.
Nests of neoplastic cells (some of which were vacu-
olated, resembling fat cells) were seen upon histo-
logical examination of the mass. In other regions,
these cells formed loosely arranged vascular chan-
nels. Due to the preponderance of these vascular chan-
nels, the most probable histological diagnosis was
hemangiosarcoma. The owner was given a poor prog-
nosis for the dog to be cured; however, a trial of
chemotherapy was elected.
One month later, the owner returned the dog for
oncologic staging of the neoplasia. Laboratory test-
ing and thoracic radiographs were within normal lim-
its. Sublumbar lymphadenopathy of possible reactive
or metastatic origin was seen on abdominal ultra-
sonography. An intravenous adriamycin (30 mg/m 2)
and cyclophosphamide (150 mg/m 2) chemotherapy
protocol, to be given every three weeks, was begun.
The dog was to be treated four times with this combi-
nation and then be monitored for evidence of disease.
One week after the first treatment, the dog became
pollakiuric, and the owner noticed an orange tint to
the urine. At this time, the referring veterinarian
placed the dog on trimethoprim-sulfadiazine (15 mg/
kg body weight, PO bid). The dog re-presented to the
UWVMTH for evaluation after 10 days with no im-
provement. A diagnosis of sterile hemorrhagic cysti-
tis was established following urinalysis and urine
culture. Cyclophosphamide therapy was discontinued.
Treatment with oxybutinin (0.3 mg/kg body weight,
PO tid), an anticholinergic agent with direct antispas-
modic activity on smooth muscle and analgesic and
local anesthetic effects, was instituted. The dog was
discharged with instructions for the owner to monitor
urination and return the dog in three weeks for tho-
July/August 1998, Vol. 34
Figure 3—Photomicrograph of a representative section of the
abdominal mass. Note the neoplastic mesenchymal cells with
prominent cytoplasmic vacuolization, typical of liposarcoma
(Hematoxylin and eosin stain, 250X; bar=20 µm).
Figure 4—Photomicrograph of the vertebral body mass showing
malignant cells surrounded by osteoid matrix (arrows), charac-
teristic of osteosarcoma (Hematoxylin and eosin stain, 250X;
bar=20 µm).
racic and abdominal radiographs prior to the next
dose of adriamycin.
Five days later, the dog became urinary and fecal
incontinent and was ataxic in the hind limbs. The
owner returned to the referring veterinarian, at which
time the dog was ataxic, paraparetic, and had patellar
hyperreflexia and conscious proprioceptive deficits
in the hind limbs. Possible causes for these neuro-
logical signs included adverse drug reaction, third
thoracic (T 3) to third lumbar (L 3) intervertebral disk
protrusion/extrusion, or other T3 -L3 lesions including
metastatic disease. The dog remained hospitalized for
six days and was treated with prednisone (0.5 mg/kg
body weight, PO bid), during which time her neuro-
logical status worsened. At this time, the owner
elected to euthanize the dog.
On gross postmortem examination, multiple vari-
cosities were noted throughout the abdominal cavity
due to venous shunting secondary to interruption of
Mesenchymoma 297
Figure 5—Low-power photomicrograph showing neoplastic in-
filtration of the wall of a large vessel. Necrotic center (N) fills the
vascular lumen (Hematoxylin and eosin stain, 25X; bar=160
µm). High-power inset of anaplastic neoplastic cells within the
wall of this vessel (Hematoxylin and eosin stain, 400X; bar=10
µm).
the caudal vena cava. In addition, upon dissection of
the vertebral column, the body of the L 3 vertebra was
soft, friable, and partially disintegrated. The verte-
bral body was discolored, dark red, and granular.
Dark red tissue was adherent to and adjacent to the
spinal cord in the area of the L 3 vertebra, and spinal
cord compression was evident. On histological ex-
amination of the L 3 vertebral body and spinal cord,
destruction of the bony mantle and replacement by an
anaplastic, mesenchymal neoplasm was seen. The tu-
mor was composed of plump, anaplastic cells (typi-
cally with large, irregular nuclei, abundant vacuolated
cytoplasm, and indistinct cell boundaries). Most of
the cells contained variably sized, clear, solitary-to-
multiple, empty vacuolar spaces suggestive of lipid
[Figure 3]. Neoplastic infiltration extended extra-
durally, sometimes wrapping around nerve roots. The
tumor was composed of varying sheets of poorly dif-
ferentiated mesenchymal cells and abundant areas of
necrosis and fibroplasia. Tumor cells tended to be
plump and irregular, with nuclei similar to those
within the vertebral body; however, localized areas of
intracytoplasmic lipid deposition were more difficult
to find. Several foci exhibited an extracellular matrix
suggestive of osteoid [Figure 4]. Within the paren-
chyma of the spinal cord, evidence of compression
with axonal swelling, axonal necrosis, and Gitter cell
accumulation was obvious. In addition, anaplastic
neoplastic cells were found in the wall of the mesen-
teric veins and a thymic vein upon examination of
tissue sections taken from the mesentery between the
adrenal glands and from the thymus [Figure 5]. The
final diagnosis was malignant mesenchymoma with
an unusual vasoinvasive metastasis.
298 JOURNAL of the American Animal Hospital Association
Discussion
Diagnosis of a malignant mesenchymoma requires
the presence of two unrelated, neoplastic cell types of
mesenchymal origin within the tumor. 2 Malignant
mesenchymoma with vasoinvasive metastasis has not
been reported previously in either humans or dogs.
Malignant mesenchymomas have been reported in
nearly every other area of the body in humans; most
often reported locations are the lungs, thoracic wall,
liver, spleen, retroperitoneal, and soft tissues of the
extremities. 4–7 These tumors have included cell types
characteristic of hemangiosarcoma, rhabdomyosar-
coma, leiomyosarcoma, liposarcoma, chondrosar-
coma, osteosarcoma, synovial cell sarcoma, and
undifferentiated sarcoma. 1 The biological behavior of
malignant mesenchymomas is unpredictable due to
their varied constituent neoplasms. 1 Although exceed-
ingly rare in dogs, mesenchymomas have been re-
ported in the lungs, liver, spleen, long bones, muscles,
and digits. 1,8–11 One report of mesenchymomas aris-
ing in the spleen found that these tumors had the
longest median survival time (12 months) after sple-
nectomy when compared with other primary mesen-
chymal tumors of the spleen. 12 Aggressive surgical
excision of solitary mesenchymomas often is reported
to be curative in humans. However, some reports
present hamartomas (which are benign mixed neo-
plasms) as mesenchymomas, which obscures the sur-
vival data. 13
The malignant mesenchymoma in this dog had two
differentiated malignant cell types, liposarcoma and
osteosarcoma. Only one case of an osteochon-
droliposarcoma in the radius of a dog has been re-
ported.14 In this report, the individual components
metastasized independently; the osteosarcoma metas-
tasized to the lungs, and the liposarcoma metasta-
sized to the axillary lymph nodes, adrenal glands, and
liver. No case reports of malignant mesenchymoma in
the vertebral column or vena cava of a dog have been
reported. In humans, several reports of malignant
mesenchymomas in the inferior vena cava and heart
were found.15–18 Malignant mesenchymoma in bone
has been reported in a number of case reports for
humans.19–21 Primary or metastatic malignant mesen-
chymomas of the central nervous system in humans
have been reported.22,23
Liposarcomas are uncommon tumors with an over-
all incidence reported to be between 0.2% and 0.5%
of all canine neoplasms. The mean age of dogs at
diagnosis is 9.7 years.3 Although no human or canine
cases of liposarcoma in the vertebral column have
been published, several cases of liposarcomas invad-
ing bone24–27 and one case of an extradural spinal
liposarcoma without primary bony invasion have been
reported. 28 Liposarcomas generally are firm but
poorly organized masses which tend to be aggressive
July/August 1998, Vol. 34
and locally invasive, often found invading veins,
muscle, fascia, and lymphatics. 3 Metastasis frequently
occurs to the lungs, liver, and bone. 3,26 These tumors
are found more often in the ventral subcutis and in the
abdominal cavity, 25,29–32 with one study reporting that
50% of the abdominal liposarcomas involved the peri-
renal fat caudal to the kidney. 33 Wide surgical exci-
sion is recommended but usually not possible due to
the invasive nature and locations of these tumors.3
The presence of osteoid in sections of the tumor
presented here indicates osteosarcomatous differen-
tiation. In humans, mesenchymomas commonly have
either osteosarcomatous or chondrosarcomatous con-
stituents or both.19–21,23,34,35 Of the canine cases of
primary axial osteosarcoma, tumors of the spine oc-
cur about 15% of the time.36 Osteosarcomas rarely
occur extraskeletally but have been reported in the
spleen, liver, kidney, bowel, adrenal gland, mammary
tissue, vagina, testicle, and eye of dogs.36 Osteosar-
coma is an extremely aggressive neoplasm, causing
osteoproliferative/osteolytic lesions which often lead
to pathological fractures. Metastasis occurs early and
can be assumed to have occurred in 90% of dogs at
the time of presentation. 36
The current case remains unique regarding the type
and location of the tumor as well as its clinical pre-
sentation. It remains unclear whether the primary tu-
mor was in the caudal vena cava with later metastasis
to the thymus and vertebral body of L 3 or if the
primary tumor was located in the body of the L3
vertebra with hematogenous metastasis elsewhere.
One plausible explanation is that the primary mass
grew in the vena cava, with progressive obstruction
of venous return and shunting of blood through the
vertebral venous veins and sinuses, ultimately seed-
ing the vertebral body of L 3. A tumor of the caudal
vena cava which eventually occluded the entire
venous return, causing minimal clinical signs, must
have grown slowly. Additionally, the widespread
vasoinvasive metastases belie the aggressive nature
of this neoplasm.
References
1. Moore RW, Snyder SP, Houchens JW, Folk JJ. Malignant mesenchymoma
in a dog. J Am Anim Hosp Assoc 1983;19:187–90.
2. Stout AP, Lattes R. Malignant mesenchymoma. In: Stout AP, Lattes R,
eds. Tumors of soft tissues. Fascicle 1, second series. Armed Forces
Institute of Pathology, 1967:172–3.
3. MacEwen EG, Withrow SJ. Soft tissue sarcomas. In: MacEwen EG,
Withrow SJ, eds. Small animal clinical oncology. Philadelphia: WB
Saunders, 1996:211–26.
4. al-Kana R, Rangwala AF, Sills C, Rienzo A. Case report: malignant
mesenchymoma of the mediastinum. New Jersey Med 1992;89(11):
851–5.
5. Mukherji SK, Rojiani AM, Younathan CM, Ros P. CT findings of
retroperitoneal malignant mesenchymoma. Abd Imaging 1994;19(1):
82–3.
July/August 1998, Vol. 34 Mesenchymoma 299

6. Newman KD, Schisgall R, Reaman G, Guzzetta PC. Malignant
mesenchymoma of the liver in children. J Pediatr Surg 1989;24(8):
781–3.
7. Sheffield M, Rao PR. Malignant mesenchymoma of the pleura. South
Med J 1996;89(5):526–8.
8. Carpenter JL, Dayal Y, King NW, Moore FM. Distinctive unclassified
mesenchymal tumor of the digit of dogs. Vet Path 1991;28:396–402.
9. Hahn KA, Richardson RC. Use of cisplatin for control of metastatic
malignant mesenchymoma and hypertrophic osteopathy in a dog. J Am
Vet Med Assoc 1989;195(3):351–3.
10. Watson AD, Young KM, Dubielzig RR, Biller DS. Primary mesenchy-
mal or mixed-cell-origin lung tumors in four dogs. J Am Vet Med Assoc
1993;202(6):968–72.
11. MacDonald RK, Helman RG. Hepatic mesenchymoma in a dog. J Am
Vet Med Assoc 1986;188(9):1052–3.
12. Spangler WL, Culbertson MR, Kass PH. Primary mesenchymal
(nonangiomatous/nonlymphomatous) neoplasms occurring in the canine
spleen: anatomic classification, immunohistochemistry, and mitotic ac-
tivity correlated with patient survival. Vet Path 1994;31:37–47.
13. Jain SK, Afzal M, Mathew M, Ramani SK. Malignant mesenchymoma
of the chest in an adult. Thorax 1993;48(4):407–8.
14. Misdorp W, Van der Heul RO. An osteo-(chondro-)liposarcoma (“ma-
lignant mesenchymoma”) of the radius in a dog, with two types of
metastases. Zbl Vet Med A 1975;22:187–92.
15. Reed HM, Poppiti R, Sivina M. Malignant mesenchymoma of kidney
and inferior vena cava. Urology 1983;22(3):297–9.
16. Kuwashima Y, Hayashi S, Arata M, Takemura T. Rhabdomyosarcoma
with focal cartilaginous differentiation (malignant mesenchymoma) of
the inferior vena cava. Acta Path Japonica 1992;42(5):382–5.
17. McKenney PA, Moroz K, Haudenschild CC, Shemin RJ, Davidoff R.
Malignant mesenchymoma as a primary cardiac tumor. Am Heart J
1992;4(1):1071–5.
18. Peters P, Flachskampf FA, Hauptmann S, Lo HB, Schuster CJ.
Bilocular atrial malignant mesenchymoma causing mitral and localized
pulmonary vein flow obstruction: diagnosis by transesophageal
echocardiography. Eur Heart J 1992;13(11):1585–8.
19. Kessler S, Mirra JM, Ishii T, Thompson JC, Brien EW. Primary
malignant mesenchymoma of bone: case report, literature review, and
distinction of this entity from mesenchymal and dedifferentiated chon-
drosarcoma. Skeletal Res 1995;24(4):291–5.
20. Reijnierse M, Kroon HM, Van der Heul RO, Mulder JD. Mesenchymoma
of bone. A case report. J Bone Joint Surg 1993;75(1):112–5.
21. Scheele PM, Von Kuster LC, Krivchenia G. Primary malignant
mesenchymoma of bone. Arch Path & Lab Med 1990;114(6):614–7.
22. Gibson JN, Reid R, McMaster MJ. Fibrocartilaginous mesenchymoma
of the fifth lumbar vertebra treated by vertebrectomy. Spine
1994;19(17):1992–7.
23. Liwnicz BH, Ferreol EC. Mixed malignant mesenchymoma metastatic
to the central nervous system. Arch Path & Lab Med 1986;110(1):85–7.
24. Brodey RS, Riser WH. Liposarcoma of bone in a dog: case report. J Am
Vet Radiolog Soc 1966;7:27–33.
25. Meierhenry EF. Metastatic liposarcoma with extensive osteolysis in the
dog. J Am Anim Hosp Assoc 1974;10:478–81.
26. Dawson EK. Liposarcoma of bone. J Path 1955;70:513–20.
27. Brodey RS, Sauer RM, Medway W. Canine bone neoplasia. J Am Vet
Med Assoc 1963;143:471–95.
28. Lewis DD, Kim DY, Paulsen DB, Kerwin SC. Extradural spinal lipo-
sarcoma in a dog. J Am Vet Med Assoc 1991;199(11):1606–7.
29. Doster AR, Tomlinson MJ, Mahaffey EA, Jordan CW. Canine liposar-
coma. Vet Path 1986;23:84–7.
30. Garvin CH, Frey DC. Liposarcoma in a dog. J Am Vet Med Assoc
1962;140:1073–5.
31. Jabara AG. Three cases of liposarcoma in dogs. J Comp Path 1964;74:
188–91.
32. Zwicker GM. Liposarcoma in a dog. Path Vet 1970;7:145–7.
33. Strafuss AC, Bozarth AJ. Liposarcoma in dogs. J Am Anim Hosp Assoc
1973;9:183–7.
34. Hassan MO, Gogate PA, Hampel N. Malignant mesenchymoma of the
prostate: immunohistochemical and ultrastructural observations. Ultra-
structural Path 1994;18(4):449–56.
35. Satake I, Tari K, Nakagomi K, Ishii M, Kishi K. Retroperitoneal malig-
nant mesenchymoma: a case report. Internat J Urol 1994;1(3):273–4.
36. Straw RC. Tumors of the skeletal system. In: MacEwen EG, Withrow SJ,
eds. Small animal clinical oncology. Philadelphia: WB Saunders,
1996:287–303.
 Merck
4C Ad
pull June Trends, p. 5

page 300
 Lymphangiosarcoma in a Dog Presenting
with Massive Head and Neck Swelling
A three-year-old, neutered male Chesapeake Bay retriever was presented for acute
onset of severe, progressive swelling of the head, neck, and cranial trunk. Diffuse
lymphangiosarcoma involving the superficial and deep dermis and subcutaneous
tissue was observed on skin biopsies. Lymphangiosarcoma is a rarely reported
tumor of the lymphatic system in dogs and cats. The importance of obtaining skin
biopsies in animals with acute edema of unknown etiology is emphasized.
Additionally, neoplasia should be considered as a potential diagnosis in a dog with
an acute onset of edema. J Am Anim Hosp Assoc 1998;34:301–4.

Theresa W. Fossum, DVM, MS, Introduction

PhD, Diplomate ACVS
Matthew W. Miller, DVM, MS,
Diplomate ACVIM
John T. Mackie, DVM, PhD,
Diplomate ACVP
Lymphangiosarcomas are extremely rare tumors that arise from lym-
phatic endothelial cells in humans and domestic animals. In humans,
they frequently occur secondary to chronic lymphedema.1–3 The pur-
pose of this report is to describe a case of lymphangiosarcoma in a
dog that presented for evaluation of sudden onset of diffuse swelling
of the head, neck, and cranial trunk.

C A three-year-old, neutered male Chesapeake Bay retriever was pre-
From the Departments of Small Animal
Medicine and Surgery (Fossum, Miller)
and Veterinary Pathobiology (Mackie),
College of Veterinary Medicine,
Texas A&M University,
College Station, Texas 77843.
Doctor Mackie’s current address is
Veterinary Pathology Services,
P.O. Box 1119,
Coorparoo DC QLD 4151, Australia.
Case Report
sented for evaluation of severe, progressive swelling of the head,
neck, and cranial trunk. The owners first had noted swelling of the
face; the swelling appeared to spread gradually over the ensuing two
months. Treatment with various antibiotics (i.e., amoxicillin, tetracy-
cline, doxycycline), diuretics, and antihistamines did not result in
obvious improvement. Respiratory difficulty was not noted; however,
the dog had become progressively more depressed and exercise intol-
erant over the past two weeks. Appetite remained good, and vomiting
or diarrhea was not noted.
On physical examination, diffuse edema of the head, neck, fore-
limbs, and cranial aspect of the trunk was noted [Figure 1]. The
edema appeared to be fluctuant, pitting, nonpainful, and confined to
the subcutaneous tissues. Differentials included cranial vena cava
obstruction due to an intraluminal mass (e.g., neoplasia, thrombus) or
extraluminal compressive lesion; arteriovenous fistula; lymphedema;
or other lymphatic obstruction.
Regenerative anemia (hematocrit, 19.1%; reference range, 37% to
55%), mild hypokalemia (potassium, 3.4 mmol/L; reference range,
3.5 to 5.0 mmol/L), hypoproteinemia (protein, 4.4 g/dl; reference
range, 5.7 to 7.8 g/dl), and mild hypoalbuminemia (albumin, 2.3 g/dl;
reference range, 2.4 to 3.6 g/dl) were present. Massive pleural effu-
sion was noted on thoracic radiographs, but pulmonary or mediastinal
masses were not evident. Pleural fluid analysis was consistent with a
modified transudate (5,452 white blood cells/µl; total protein, 2.4
g/dl), and the cells were mainly nondegenerative neutrophils with a
moderate number of red blood cells (RBCs).
Ultrasonography was performed to evaluate the thoracic inlet and
mediastinal structures. Although cavitated fluid was present within

JOURNAL of the American Animal Hospital Association 301

302 JOURNAL of the American Animal Hospital Association
Figure 1—Photograph of a Chesapeake Bay retriever with
acute, massive swelling of the head, neck, and cranial trunk
associated with cutaneous lymphangiosarcoma.
the mediastinum, masses were not visualized. Ob-
struction or abnormalities were not noted when the
jugular veins were imaged. A nonselective angiogram
was performed to evaluate further the patency of the
cranial vena cava. Contrast appeared to flow freely
through the vessel, and no intraluminal or extralumi-
nal mass was identified. Normal cardiac function was
identified on echocardiography, and an intracardiac
lesion was not seen.
Trial therapy with prednisone (2 mg/kg body
weight, per os [PO] bid) and furosemide (4 mg/kg
body weight, PO bid) was initiated and resulted in
moderate reduction of the edema; however, the dog
became increasingly anorectic over the next few days,
necessitating potassium supplementation. The dog
was placed under general anesthesia, and cervical
radiographs were obtained which were normal.
Lymphoscintigraphy was performed by injecting ra-
diolabeled sulfur colloid near the nose. An apparent
absence of lymphatic flow beyond the region of the
mandibular lymph nodes was noted. Due to the pro-
gressive anorexia, gastroduodenoscopy was per-
formed, and a large amount of free gastric blood was
found, but no obvious ulceration. Gastric and duode-
July/August 1998, Vol. 34
Figure 2—Photomicrograph of a section of facial skin showing
wide separation of preexisting collagen bundles and their envel-
opment by plump spindle cells (Hematoxylin and eosin stain,
860X).
nal biopsies were obtained through the endoscope.
Additionally, two punch biopsies were taken from the
skin on the ventral aspect of the neck. Copious
amounts of fluid drained from the cutaneous biopsy
sites.
Abnormalities were not observed in the gastric or
duodenal biopsies. Diffuse lymphangiosarcoma in-
volving the superficial and deep dermis and subcuta-
neous tissues was seen on skin biopsies. Thin,
irregular, preexisting collagen bundles were lined gen-
erally by a single layer of plump spindle cells and
were separated widely by clear spaces devoid of RBCs
[Figure 2]. Underlying skeletal muscle fibers also
were lined by plump spindle cells. These cells were
characterized by cytoplasm which was scant and
weakly eosinophilic to amphophilic and by nuclei
which were oval-to-elongated, slightly pleomorphic,
7-to-15 µm long, and hyperchromatic with little in-
ternal detail. The same cells also were present in
large numbers both individually and in clusters in the
clear spaces between collagen bundles, and in some
places they were congregated upon collagen bundles.
Mitotic figures were rare. Initially these changes were
thought to be consistent with an obstructive lym-
phatic disease process. However, after the slides were
reviewed carefully, the neoplastic nature of the lesion
was identified. Lymphatic neoplasia was confirmed
by immunohistochemical examination of tissues per-
formed at the Armed Forces Institute of Pathology in
Washington, DC, which demonstrated positive stain-
ing for the presence of Factor VIII-related antigen
(FVIIIR:Ag) and vimentin in the cytoplasm of these
cells.
Discussion
The diagnosis of lymphangiosarcoma was confirmed
by evaluation of skin biopsies from the edematous
tissues; this emphasizes the importance of obtaining
biopsies in animals with unexplained subcutaneous
July/August 1998, Vol. 34
edema. Earlier biopsy of affected tissues may have
reduced the number of diagnostic tests performed in
this dog, resulting in less expense and a more rapid
diagnosis. Lymphoscintigraphy, although valuable in
defining the degree of lymphatic obstruction present
in this dog, did not contribute to the diagnosis of
neoplasia and may be less important than biopsy in
dogs with lymphedema, regardless of cause.
Neoplasia should not be excluded as a potential
diagnosis in dogs with an acute onset of swelling.
Although acute head, neck, and forelimb swelling
(i.e., cranial caval syndrome) is more commonly
thought of as being caused by vascular occlusion,
similar signs may occur due to progressive obstruc-
tion of lymphatics by neoplastic cells or tissue. Fur-
thermore, in most dogs with experimental occlusion
of the cranial vena cava, collateral blood flow mini-
mizes head and neck swelling; however, many af-
fected dogs develop chylothorax. 4 A necropsy was
not performed in this dog, so the cause of the pleural
effusion was not identified. However, it most likely
was due to neoplastic obstruction of intrathoracic lym-
phatics, resulting in transudation of lymph into the
pleural space. The cause of the gastric bleeding is
uncertain, but it may have been related to steroid
therapy.
Congenital lymphedema may be noted first in
middle-aged dogs, and thus the age in this dog did not
preclude a diagnosis of congenital lymphedema. How-
ever, in most dogs with congenital lymphedema, the
limbs are affected more severely than the head and
neck. 5,6 Lymphangiosarcoma is a rarely reported tu-
mor of the lymphatic system in dogs and cats. 7–14 It
has been diagnosed at necropsy in animals presenting
for evaluation of chronic lymphedema. Occasionally,
it has been associated with chylous effusions into the
thoracic or abdominal cavities or subcutaneous
spaces.8,15,16 A clear breed or sex predisposition has
not been identified in dogs, but medium- and large-
breed dogs may be affected more commonly.17 Al-
though too few cases have been reported to determine
the biological behavior of this tumor, metastasis has
been present in most dogs with lymphangiosarcoma
at necropsy. 7,10,11,17 However, surgical excision of a
localized mass without clinical evidence of metasta-
sis has been reported in a female poodle with lym-
phangiosarcoma.18 In humans, this tumor occurs most
commonly in patients with chronic lymphedema, and
some authors have suggested that the tumor develops
because of local immunodeficiency associated with
the lymphedema; 1–3 however, the physical pressure
imposed on the endothelium by chronic lymphedema
may be a more plausible trigger. Stark, et al. found
that in vivo transplantation of lymphangiosarcoma to
the extremity of a lymphedematous limb was more
successful than if the tumor was transplanted to a
Lymphangiosarcoma 303
healthy limb.19 The acute onset of lymphedema in
this dog would suggest that the tumor caused the
lymphedema rather than arose secondary to the
lymphedema.
Histologically, it can be difficult to differentiate
tumors that arise from lymphatic endothelium from
those of blood vessel endothelial origin. In this case,
the histological features of envelopment of preexist-
ing collagen bundles and skeletal muscle fibers, the
lack of significant RBCs within spaces, and the promi-
nent edema seen grossly are consistent with previous
reports of lymphangiosarcoma in humans,20–22 the
dog, 7,10,11 and the cat. 8,9,23 Human FVIIIR:Ag is
present in both lymphatic and blood vessel endothe-
lial cells. 24 The positive staining for FVIIIR:Ag and
vimentin confirms that this tumor was of endothelial
origin.
Conclusion
Lymphangiosarcoma should be considered as a pos-
sible differential diagnosis in dogs presenting with an
acute onset of lymphedema. Biopsy of affected tis-
sues may be diagnostic and should be performed in dogs
that have no obvious explanation for their swelling.
References
1. Tomita K, Yokogawa A, Oda Y, et al. Lymphangiosarcoma in
postmastectomy lymphedema (Stewart-Treves syndrome): ultrastruc-
tural and immunohistologic characteristics. J Surg Oncol 1988;38:
275–82.
2. Eby CS, Brennan MJ, Fine G. Lymphangiosarcoma: a lethal complica-
tion of chronic lymphedema. Arch Surg 1967;94:223–30.
3. Woodward AH, Ivins JC, Soule EH. Lymphangiosarcoma arising in
chronic lymphedematous extremities. Cancer 1972;30:562–72.
4. Fossum TW, Birchard SJ. Lymphangiographic evaluation of experimen-
tally induced chylothorax after ligation of the cranial vena cava in dogs.
Am J Vet Res 1986;47:967–71.
5. Fossum TW, King LA, Miller MW, et al. Lymphedema: clinical signs,
diagnosis, and treatment. J Vet Int Med 1992;6:312–9.
6. Fossum TW, Miller MW. Lymphedema—etiopathogenesis. J Vet Int
Med 1992;6:283–93.
7. Rudd RG, Veatch JK, Whitehair JG, et al. Lymphangiosarcoma in dogs.
J Am Anim Hosp Assoc 1989;25:695–8.
8. Stobie D, Carpenter JL. Lymphangiosarcoma of the mediastinum, mes-
entery, and omentum in a cat with chylothorax. J Am Anim Hosp Assoc
1993;29:78–80.
9. Walsh KM, Abbott DP. Lymphangiosarcoma in two cats. J Comp Path
1984;94:611–4.
10. Kelly WR, Wilkinson GT, Allen PW. Canine angiosarcoma (lymphan-
giosarcoma): a case report. Vet Path 1981;18:224–7.
11. Franklin RT, Robertson JJ, Thornburg LP. Lymphangiosarcoma in a
dog. J Am Vet Med Assoc 1984;184:474–5.
12. Patnaik AK, Liu S-K. Angiosarcoma in cats. J Sm Anim Pract
1977;18:191.
13. Patnaik AK, Liu S-K, Hurvitz AI, et al. Nonhematopoietic neoplasms in
cats. J Natl Cancer Inst 1975;54:855–60.
14. Lamb WA, Muir P. Lymphangiosarcoma associated with hyponatremia
and hyperkalemia in a dog. J Sm Anim Pract 1994;35:374–6.
15. Fossum TW, Hodges CC, Scruggs DW, et al. Generalized lymphan-
giectasis in a dog with subcutaneous chyle and lymphangioma. J Am Vet
Med Assoc 1990;197:231–6.
(Continued on next page)
304 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

References (cont’d) 20. Lattes R. Tumors of the soft tissues. In: Hartmann WH, Cowan WR, eds.
Atlas of tumor pathology. Washington, DC: Armed Forces Institute of
16. Myers NCI, Engler SJ, Jakowski RM. Chylothorax and chylous ascites Pathology, 1982:205–9.
in a dog with mediastinal lymphangiosarcoma. J Am Anim Hosp Assoc
21. Malignant vascular tumors. In: Enzinger FM, Weiss SW, eds. Soft tissue
1996;32:263–9.
tumors. 2nd ed. St. Louis: Mosby, 1988:545–56.
17. Sagartz JE, Lairmore MD, Haines D, et al. Lymphangiosarcoma in a
22. Tumours of vasoformative tissue. In: Ashley DJB, ed. Evans’ histologi-
young dog. Vet Path 1996;33:353–6.
cal appearances of tumours. 4th ed. Edinburgh: Churchill Livingstone,
18. Shiga A, Shirota K, Une Y, et al. Lymphangiosarcoma in a dog. J Vet 1990:99–101.
Med Sci 1994;56:1199–202.
23. Swayne DE, Mahaffey EA, Haynes SG. Lymphangiosarcoma and
19. Stark RB, Dwyer EM, Forest MD. Effect of surgical ablation of regional hemangiosarcoma in a cat. J Comp Path 1989;100:91–6.
lymph nodes on survival of skin homografts. Ann N Y Acad Sci
24. Burgdorf WHC, Mukai K, Rosai J. Immunohistochemical identifica-
1960;87:140–8.
tion of factor VIII-related antigen in endothelial cells of cutaneous
lesions of alleged vascular nature. Am J Clin Path 1981;75:167–71.
 Spinal Epidural Empyema in Two Dogs
Extensive, diffuse, epidural spinal cord compression was visualized myelographically
in two dogs presented for rapid development of nonambulatory tetraparesis and
paraplegia, respectively. Purulent fluid containing bacterial organisms was aspirated
percutaneously under fluoroscopic guidance from the epidural space of each dog.
One dog responded poorly to aggressive medical therapy, which included installation
of an epidural lavage and drainage system. Both dogs were euthanized due to the
severe nature of their disorder and the poor prognosis. Spinal epidural empyema
(i.e., abscess) is a rare condition in humans and has not been reported previously
in the veterinary literature. Spinal epidural empyema should be considered as a
differential diagnosis in dogs presenting with painful myelopathies, especially when
accompanied by fever. J Am Anim Hosp Assoc 1998;34:305–8.

Curtis W. Dewey, DVM, MS, Introduction

Diplomate ACVIM, Bacterial infections of the central nervous system (CNS) are not
Diplomate ACVS
reported commonly in dogs and cats. Potential sources for CNS bac-
Gregg D. Kortz, DVM, terial infections include hematogenous spread and direct extension
Diplomate ACVIM from a nearby contaminated or infected area.1–3 Spinal epidural em-
pyema (i.e., abscess), an accumulation of purulent material in the
Cleta S. Bailey, DVM, PhD, epidural space of the vertebral canal, is a rare disorder in humans and
Diplomate ACVIM has not been documented in dogs. Hallmarks of the human disease
include spinal hyperesthesia and fever. Diagnosis of spinal epidural
empyema often is delayed in humans because of its rarity and nonspe-
C cific clinical signs. Unfortunately, delays in diagnosis and appropri-
ate treatment are associated with an increased likelihood of permanent
neurological dysfunction or death.4–13
Two dogs with initial clinical signs of spinal hyperesthesia and
fever each progressed to nonambulatory status within a 24-hour pe-
riod. The dogs had purulent, epidural fluid accumulations causing
spinal cord compression. The purposes of this report are to describe
the clinical and myelographic findings of these two dogs with spinal
epidural empyema and to review the current literature concerning this
disease in humans.

Case Reports

From the Veterinary Medical Teaching
Hospital (Dewey, Kortz) and the
Department of Surgical and Radiological
Sciences (Bailey),
University of California,
Davis, California 95616.
Doctor Dewey’s current address is the
Department of Small Animal Medicine
and Surgery,
College of Veterinary Medicine,
Texas A&M University,
College Station, Texas 77843-4474.
Case No. 1
A two-year-old, intact male Irish wolfhound presented to the Univer-
sity of California-Davis Veterinary Medical Teaching Hospital (UCDVMTH)
following neck and back pain of nine days’ duration that had pro-
gressed to nonambulatory tetraparesis 24 hours prior to admission.
The owner noted that the dog was experiencing pain shortly after a
hike they had taken in a wooded area. The patient had been examined
by two veterinarians prior to referral to the UCDVMTH. The dog had
been found to be febrile as well as in pain and was treated with
glucocorticoids, nonsteroidal anti-inflammatories, a first-generation
cephalosporin, and enrofloxacin. Upon physical examination, the pa-
tient was depressed, febrile (105˚ F), and reacted painfully to palpa-
tion of the cervical and caudal thoracic spinal regions. Upon
neurological examination, the patient was found to be nonambulatory

JOURNAL of the American Animal Hospital Association 305

306 JOURNAL of the American Animal Hospital Association
A A
Figures 1A, 1B—Myelographic appearance of epidural empy-
ema in case no. 1. The arrows indicate the ventral displacement
of the dorsal contrast column by epidural fluid in the (A) cervical
and (B) thoracolumbar regions of the spine. (Courtesy of Phil
Koblik, DVM, MS, Diplomate ACVR).
tetraparetic with intact spinal reflexes. Due to the
multiple areas of spinal hyperesthesia, a multifocal or
diffuse myelopathy (rather than a focal, cervical spi-
nal cord lesion) was suspected. Hematological and
serum biochemical profile abnormalities included a
mature neutrophilia with lymphopenia, thrombocy-
topenia, mild hypoalbuminemia, hypercholesterolemia,
and increased levels of alkaline phosphatase and cre-
atine kinase. Fibrinogen levels also were elevated.
The patient was anesthetized, and survey radio-
graphs of the spine were obtained. Slight narrowing
at the sixth cervical (C 6) to seventh cervical (C7)
intervertebral disk space, with dorsal tipping of the
cranial aspect of the C 7 vertebra, was appreciated on
the survey radiographs. A lumbar cerebrospinal fluid
(CSF) sample was analyzed prior to injection of
iopamidol for the myelogram. This CSF included 81
red blood cells (RBCs)/µl, three nucleated cells/µl
(73% neutrophils, 27% mononuclear cells), and a pro-
tein level of 153 mg/dl. This was interpreted as mild
purulent inflammation. A cerebellomedullary CSF
sample was obtained and appeared to be blood con-
taminated. This sample was analyzed as the myelo-
gram was being performed. This CSF contained
22,600 RBCs/µl, 4,800 nucleated cells/µl (96% neu-
trophils, 4% mononuclear cells), and a protein level
of 2,106 mg/dl. This fluid was interpreted as purulent
inflammation. No organisms were seen in either CSF
sample. Severe dorsal compression of the spinal cord
from the first cervical (C 1) to third cervical (C3 ) and
the third thoracic (T3) to first lumbar (L 1 ) vertebral
segments was identified on myelography [Figures 1A, 1B].
July/August 1998, Vol. 34
Figures 2A, 2B—Radiographs demonstrating the placement of
epidural catheters in the (A) cervical and (B) thoracolumbar
spinal regions of case no. 1. The catheters were to serve as an
ingress-egress system for lavage of the epidural space. (Cour-
tesy of Phil Koblik, DVM, MS, Diplomate ACVR).
A needle aspirate of the epidural space was per-
formed dorsally at the L 1 to second lumbar (L 2) inter-
vertebral level under fluoroscopic guidance. An
opaque, orange-colored fluid was retrieved. Numerous
degenerative neutrophils and abundant gram-positive
cocci (the latter of which were arranged frequently in
chains) were identified on cytological examination of
the epidural fluid. Bacterial organisms subsequently
were cultured from the epidural fluid and identified
as beta-hemolytic Streptococcus canis. Blood cul-
tures also were positive for the same organism. After
obtaining the cytology report, two polypropylene
catheters were placed in the dorsal epidural space,
under fluoroscopic guidance. One was placed at the
C 1 to second cervical (C 2 ) intervertebral level and the
other was placed at the 13th thoracic (T 13) to the L 1
intervertebral level [Figures 2A, 2B]. These catheters
were to serve as an ingress-egress system for lavage
of the epidural space.
The patient was transferred to the intensive care
unit (ICU) and placed on intravenous fluid and antibi-
otic therapy (i.e., ticarcillin and clavulanic acid). The
dog experienced a respiratory arrest and was intu-
bated. The patient did not regain consciousness after
the arrest and had to be placed on ventilatory support,
as there were no spontaneous efforts to breathe. Due
to the poor prognosis, the owner elected to have the
dog euthanized. Upon necropsy examination, puru-
lent fluid was evident throughout the entire spinal
epidural space, with the largest accumulation in the
area of the L 1-L 2 intervertebral space. Histopathology
results included evidence of a diffuse, severe, fibri-
nopurulent meningomyelitis and a mild, neutrophilic
cerebral meningitis.
Case No. 2
A two-year-old, intact male Irish wolfhound presented
to the UCDVMTH for anorexia and inactivity of four
days’ duration. On the morning of admission, the dog
July/August 1998, Vol. 34
A (L3 ) to fourth lumbar (L4) intervertebral level. The
B thromboplastin time. These were within normal lim-
Figures 3A, 3B—Myelographic appearance of epidural empy-
ema in case no. 2. The arrows indicate the ventral displacement
of the dorsal contrast column by epidural fluid in the (A) cranial
thoracic and (B) thoracolumbar regions of the spine. (Courtesy
of Phil Koblik, DVM, MS, Diplomate ACVR).
had become paraplegic. On physical examination, the
patient was found to be depressed, moderately dehy-
drated, febrile (106.4˚ F), and tachypneic, with bloody
diarrhea and scleral hyperemia. The patient appeared
to be in pain when the thoracolumbar and lumbosac-
ral regions of the spine were palpated. Findings of a
neurological examination included a miotic right pu-
pil, purposeful motor function and intact spinal re-
flexes in the thoracic limbs, and absence of motor
function, spinal reflexes, and deep pain perception in
the pelvic limbs. A diffuse-to-multifocal myelopathy,
from the T 3 to first sacral (S 1) spinal cord seg-
ments, was suspected based upon the neurological
examination. Hematological and serum biochemi-
cal profile abnormalities included a mature neutro-
philia with lymphopenia, mild elevations of blood
urea nitrogen (BUN) and creatinine, mildly increased
total bilirubin, increased alkaline phosphatase lev-
els, hypercholesterolemia, and hyperfibrinogenemia.
The patient was anesthetized, and survey radio-
graphs of the spine were obtained. No abnormalities
were evident on these radiographs. A lumbar CSF
sample was analyzed, and the results included 282,000
RBCs/µl, 340 nucleated cells/µl (86% neutrophils,
14% mononuclear cells), and a protein level of 209
mg/dl. This was interpreted as hemorrhagic CSF. A
myelogram was performed via lumbar injection of
iopamidol. A space-occupying lesion in the dorsal
epidural space from the fourth thoracic (T4 ) to sixth
lumbar (L 6) vertebral levels was identified, compress-
ing the spinal cord [Figures 3A, 3B]. Under fluoro-
scopic guidance, a needle aspirate of the dorsal
epidural space was obtained from the third lumbar
Spinal Epidural Empyema 307
fluid retrieved was hemorrhagic and viscous. Cyto-
logical findings from this fluid included a small num-
ber of gram-positive cocci among neutrophils and
numerous RBCs. Subsequent culture of this epidural
fluid yielded Staphylococcus intermedius and Clostrid-
ium perfringens. Blood cultures also were positive
for both organisms. The hemorrhagic nature of both
the diarrhea and epidural fluid in this dog prompted
measurement of a prothrombin time and a partial
its. Due to the poor prognosis for recovery, the owner
elected to euthanize the patient. Necropsy results in-
cluded abundant hemorrhagic fluid in the epidural
space from the T 4 vertebral level caudally, as well as
hemorrhagic gastrointestinal contents. The mucosa of
the jejunum and ileum were reddened diffusely. Se-
vere epidural and intradural hemorrhage from the T4
spinal cord segment to the level of the cauda equina
was evident on histopathology. Pathological changes
within the cord were limited to focal areas of is-
chemic neuronal necrosis and intraparenchymal he-
morrhage. No gross or histopathological evidence of
a coagulopathy was identified.
Discussion
Spinal epidural empyema has not been reported pre-
viously in dogs. The authors prefer the terminology
“empyema” over “abscess” to describe the disorder,
as the former term more accurately describes the ex-
tent of the purulent fluid accumulation.14 Both cases
had exhibited vague and nonspecific clinical signs
before deteriorating neurologically, a scenario de-
scribed in the human counterpart of the disease. Both
cases also presented with clinical signs of spinal hy-
peresthesia and fever, recognized as hallmarks of spi-
nal epidural empyema in humans. 4–13
Spinal epidural empyema is a rare disease in hu-
mans. 4–13 Most physicians never encounter this dis-
ease in their professional careers.5 The rarity of spinal
epidural empyema, combined with the relatively non-
specific, typical clinical signs, often results in a delay
in diagnosis. 4–13 Neurological deterioration can
progress rapidly. 6–8,11–13 Patients rarely regain neuro-
logical function if they are paralyzed for more than
24-to-48 hours before a definitive diagnosis is reached
and appropriate treatment instituted.7,11,12 Delayed di-
agnosis and therapy also are associated with an in-
creased mortality rate;5,7–10,12 therefore, a high index
of suspicion is required in order to identify patients
with this disease rapidly and to treat them successfully.
A number of bacterial etiological agents have been
reported, the most common being Staphylococcus
aureus. 4–13 Species of Streptococcus also are impli-
cated frequently. 5,7,8,11,15 While the source of infec-
tion not always is identified, skin infections are
308 JOURNAL of the American Animal Hospital Association
thought to be the most common source. 5,8,11 Blood
cultures often yield the same organism found in the
epidural space. 7 The pathophysiological mechanisms
responsible for neurological dysfunction may include
both direct compression of neural tissue by purulent
material as well as impairment of intrinsic spinal cord
vasculature. 5,7,8,11,13 Factors that may predispose hu-
mans to spinal epidural empyema include spinal
trauma, diabetes mellitus, immunosuppression, intra-
venous drug use, and alcoholism. 7,9,12,13 Evidence of
accompanying vertebral osteomyelitis is seen in less
than 50% of the cases. 7,8,11,12 Cerebrospinal fluid
analysis often yields a mixed pleocytosis and elevated
protein levels.5–8,10–12 Diagnosis of spinal epidural
empyema can be aided by myelography, computed
tomography (CT), or magnetic resonance imaging
(MRI). Traditionally, myelography has been the diag-
nostic tool of choice; MRI is preferred currently due
to its noninvasive nature. 4–13,15,16–19
Some controversy exists concerning medical ver-
sus surgical treatment of spinal epidural empyema.
Most authors advocate surgical drainage in combina-
tion with antibiotic therapy.4–13 However, consider-
able success has been reported with nonsurgical
management of this disorder. 4,5,9,11,18,20 In some situa-
tions, nonsurgical management has been regarded as
the preferred mode of therapy.5,11,12 Indications for
nonsurgical treatment include 1) patients who are poor
surgical candidates; 2) an extensively long lesion, for
which a laminectomy would be impractical and possi-
bly lead to vertebral instability; 3) lack of severe
neurological deficits; and 4) complete paralysis for
more than 72 hours. 5,11,12
Both dogs described in this report had extensive
accumulations of fluid extending over multiple verte-
bral segments. The reason for the hemorrhagic nature
of the epidural fluid in case no. 2 remains unknown.
A potential source of infection was not identified in
case no. 1, but blood cultures were positive for the
same organism found in the epidural fluid. Case no. 2
had enteritis and associated hemorrhagic diarrhea,
making the gastrointestinal tract a likely source of
infection. The same two organisms each were cul-
tured from the epidural fluid and blood from case no.
2. An epidural drainage and lavage system was placed
successfully in case no. 1, similar to a system used in
humans with spinal epidural empyema.21 Unfortu-
nately, this patient was euthanized due to systemic
complications before this therapy could be evaluated.
Case no. 2 was euthanized without attempting therapy,
due to the poor prognosis. Interestingly, both patients
were young, male Irish wolfhounds. While this may
be a simple coincidence, it is unusual for the only two
reported cases of such a reputedly rare disease to
occur in the same breed. The possibility of an im-
mune-deficiency problem in Irish wolfhounds also
July/August 1998, Vol. 34
should be considered. To the authors’ knowledge,
such an immune-deficiency disorder has not been de-
scribed in this breed.
As demonstrated in this report, spinal epidural em-
pyema should be included on the differential diagno-
sis list for canine myelopathies. It would appear from
the rapid deterioration and ultimate death of these
two dogs, that, similar to the analogous human dis-
ease, timely diagnosis is paramount to successful
therapy. A high index of suspicion should be main-
tained for spinal epidural empyema, especially in the
dog with a painful myelopathy accompanied by fever.
References
1. Braund KG. Neurological diseases. In: Braund KG, ed. Clinical syn-
dromes in veterinary neurology. 2nd ed. St. Louis: Mosby-Year Book,
1994:81–332.
2. Fenner WR. Bacterial infections of the central nervous system. In:
Greene CE, ed. Infectious diseases of the dog and cat. 2nd ed. Philadel-
phia: WB Saunders, 1990:184–96.
3. Dow SW, LeCouteur RA, Henik RA, Jones RL, Poss ML. Central
nervous system infection associated with anaerobic bacteria in two
dogs and two cats. J Vet Int Med 1988;2:171–6.
4. Lange M, Tiecks F, Schielke E, Yousry T, Haberl R, Oeckler R. Diagno-
sis and results of different treatment regimes in patients with spinal
abscesses. Acta Neurochir (Wien) 1993;125:105–14.
5. Maslen DR, Jones SR, Crislip MA, Bracis R, Dworkin RJ, Flemming JE.
Spinal epidural abscess: optimizing patient care. Arch Int Med
1993;153:1713–21.
6. King M. Spinal epidural abscess: an elusive diagnosis. South Med J
1994;87(2):288–9.
7. Darouiche RO, Hamill RJ, Greenberg SB, Weathers SW, Musher DM.
Bacterial spinal epidural abscess: review of 43 cases and literature
survey. Medicine 1992;71(6):369–85.
8. Baker AS, Ojemann RG, Swartz MN, Richardson EP. Spinal epidural
abscess. N Engl J Med 1975;293(10):463–8.
9. Curling OD, Gower DJ, McWhorter JM. Changing concepts in spinal
epidural abscess: a report of 29 cases. Neurosurg 1990;27(2):185–92.
10. Danner RL, Hartman BJ. Update of spinal epidural abscess: 35 cases and
review of the literature. Rev Infect Dis 1987;9(2):265–74.
11. Carey ME. Infections of the spine and spinal cord. In: Youmans JR, ed.
Neurological surgery: a comprehensive reference guide to the diagnosis
and management of neurosurgical problems. 4th ed. Vol. 5. Philadel-
phia: WB Saunders, 1996:3270–304.
12. Simpson RK, Azordegan PA, Sirbasku DM, Weathers SW, Lidsky MD,
Baskin DS. Rapid onset of quadriplegia from a panspinal epidural
abscess. Spine 1991;16(8):1002–5.
13. McGee-Collett M, Johnston IH. Spinal epidural abscess: presentation
and treatment—a report of 21 cases. Med J Aust 1991;155:14–7.
14. Anderson DM, ed. Dorland’s illustrated medical dictionary. 28th ed.
Philadelphia: WB Saunders, 1994:546.
15. Gelfand MS, Bakhtian BJ, Simmons BP. Spinal sepsis due to Streptococ-
cus milleri: two cases and review. Rev Infect Dis 1991;13:559–63.
16. Spiegelmann R, Findler G, Faibel M, Ram Z, Shacked I, Sahar A.
Postoperative spinal epidural empyema: clinical and computed tomogra-
phy features. Spine 1991;1(10):1146–9.
17. Browman MW, Lapointe JS. Spinal epidural abscess: unusual CT and
microbiologic findings. Can Assoc Radiol J 1993;44(3):215–6.
18. Hanigan WC, Asner NG, Elwood PW. Magnetic resonance imaging and
the nonoperative treatment of spinal epidural abscess. Surg Neurol
1990;34:408–13.
19. Teman AJ. Spinal epidural abscess: early detection with gadolinium
magnetic resonance imaging. Arch Neurol 1992;49:743–6.
20. Wheeler D, Keiser P, Rigamonti D, Keay S. Medical management of
spinal epidural abscesses: a case report and review. Clin Infect Dis
1992;15:22–7.
21. Cwikiel W. Percutaneous drainage of abscess in psoas compartment and
epidural space. Acta Radiologica 1991;32:159–61.
 Surgical and Chemotherapeutic Treatment
of Alveolar Echinococcosis in a Dog
Surgical removal of macroscopically detectable metacestode tissue followed by
postoperative chemotherapy according to established human protocols resulted in
complete clinical remission and immediate normalization of hyperglobulinemia in a
dog with alveolar echinococcosis (AE). The disease is caused by the metacestode
stage of the cestode, Echinococcus multilocularis. In endemic areas, AE should be
included in the differential diagnosis of polycystic liver masses, especially if
concomitant hyperglobulinemia is present. However, the importance of AE is not
only the disease of the single dog itself but also the potential risk of infection for
humans in an endemic area. J Am Anim Hosp Assoc 1998;34:309–14.

Markus Haller, Dr. med. vet. Case Report

Peter Deplazes, Dr. med. vet.
Franco Guscetti, Dr. med. vet.
Juan C. Sardinas, DVM,
Diplomate ACVS
Iris Reichler, Dr. med. vet.
Johannes Eckert,
Prof. Dr. med. vet.
C biochemistry, urinalysis, thoracic and abdominal radiographs, and
From the Veterinary Teaching Hospital,
Department of Veterinary Internal
Medicine (Haller),
Institute of Parasitology
(Deplazes, Eckert),
Institute of Veterinary Pathology
(Guscetti),
Department of Veterinary Surgery
(Sardinas, Reichler),
University of Zürich,
Winterthurerstr 260, CH-8057 Zürich.
Doctor Haller’s current address is
Kleintierklinik Dr. Bolliger,
Kieferstrasse 2, CH-4665 Oftringen.
In October 1995, a 10-year-old, male dachshund was presented to the
University of Zürich Veterinary Teaching Hospital with a history of
gradually progressive abdominal enlargement. Earlier the dog had
developed general exercise intolerance. Food and water intake was
normal, and the dog was alert with no other clinical signs of illness.
The dog had never been used as a hunting dog, but catching mice was
reported to be one of his favorite habits. Upon physical examination,
the dog was excited, in good general condition, and had a pendulous
abdomen and a rectal temperature of 39.3˚ C. Upon palpation, a large,
lobulated mass was found occupying the entire abdominal space. No
other abdominal organs could be identified on palpation. Initial diag-
nostic evaluation included a complete blood count (CBC), serum
abdominal ultrasonography.
A lobulated mass filling the abdomen and displacing the stomach
dorsally and small intestine caudodorsally [Figure 1] was noted on
abdominal radiographs. Thoracic radiographs were within normal
limits. On ultrasonographic examination, the abdominal mass was
very heterogeneous, consisting of nodular parts with high echogeni-
city and cavernous parts with lower echogenicity [Figure 2]. Some of
the cavernous parts appeared to be filled with fluid. The liver was
presumed to be the origin of the mass, but several liver lobes of
normal texture and echogenicity also were identified.
The only hematological change found was a mild, nonregenerative
anemia (packed cell volume, 36%). Biochemical changes included a
marked hyperproteinemia (protein, 114 g/L; reference range, 59 to 67
g/L), hypoalbuminemia (albumin, 26 g/L; reference range, 27 to 37
g/L), hypocholesterolemia (cholesterol, 3.0 mmol/L; reference range,
4.2 to 8.6 mmol/L), and a mildly elevated creatine kinase activity
(255 U/L; reference range, 68 to 197 U/L). All other parameters
including hepatic enzyme activities were within normal limits. Urine
protein/creatinine ratio was 0.8. A serum electrophoresis was per-
formed; hypergammaglobulinemia was the cause of the hyperpro-
teinemia [Figure 3].
Under ultrasonographic guidance, a fine-needle aspirate of the
abdominal mass was made, and several milliliters of a milky fluid

JOURNAL of the American Animal Hospital Association 309

310 JOURNAL of the American Animal Hospital Association
Figure 1—Lateral abdominal radiograph of a male dachshund
presented for gradual abdominal enlargement. A lobulated
mass is seen displacing the stomach dorsally and the small
intestines caudodorsally.
Figure 2—Ultrasonographic examination of the mass, showing
a heterogenous echogenicity and multiple, cavernous, fluid-
filled structures.
were removed for analysis. The specific gravity of
the fluid was 1.041, protein was 68 g/L, and triglycer-
ide concentration was below the detectable range.
Approximately 1,000 cells/µl were counted; most of
them were damaged severely. Cytological evaluation
of the fluid revealed cellular debris, with occasional
plasma cells and mesenchymal cells that had irregular
nucleoli and a coarse chromatin pattern. Cytology did
not allow a definitive diagnosis.
A ventral midline exploratory laparotomy was per-
formed. A large, bilobar mass was found occupying
much of the abdominal cavity. The mass was firm,
pale yellow-to-white, with multiple surface lobula-
tions. It measured 13-to-15 cm in diameter [Figure 4].
The mass originated from the left-medial and right-
lateral liver lobes; the other liver lobes appeared nor-
mal. Complete lobectomy of the affected liver lobes
was performed, and the whole mass was removed. A
small mass, 2-to-3 mm in diameter, which appeared
grossly similar to the primary mass, also was re-
July/August 1998, Vol. 34
Figure 3—Serum electrophoresis before initiation of treatment,
identifying a hypergammaglobulinemia as the cause of the
hyperproteinemia.
Figure 4—Intraoperative photograph of the firm, pale yellow-to-
white, abdominal mass. Note the multiple surface lobulations.
moved from the omentum. All other abdominal or-
gans appeared normal. The resected liver lobes and
omental mass were submitted for histopathology.
Histologically, the hepatic mass consisted of nu-
merous cystic structures, each of which was lined by
a thin (10-to-15 µm), acellular, laminated layer which
was folded irregularly [Figure 5]. This layer was peri-
odic-acid-Schiff (PAS) positive. In some of the cysts,
a thin and delicate layer consisting of flattened cells
with small nuclei was seen on the inner side of the
acellular membrane. The cysts were filled with amor-
phous material, and some contained a few calcareous
bodies. Necrotic material with areas of calcification
surrounded the cysts and was delineated by active
granulation tissue with neutrophils, plasma cells, and
a few lymphocytes. Focally there was a granuloma-
tous inflammation with single, multinucleated giant
July/August 1998, Vol. 34
Figure 5—Hepatic cyst of Echinococcus multilocularis consist-
ing of an acellular membrane which includes few cells and
amorphous material. The cyst is embedded in necrotic tissue
surrounded by a granulomatous type of reaction with granula-
tion tissue (Hematoxylin and eosin stain, 300X; bar=50 µm).
cells. The histological findings were considered to be
typical for metacestodes of the tapeworm Echinococ-
cus multilocularis (E. multilocularis), although no
protoscoleces were identified. 1 The metacestode stage
of E. multilocularis is known as alveolar echinococ-
cosis (AE).
Following histological diagnosis, serology was per-
formed by enzyme-linked immunosorbent assay
(ELISA) using antigens (the metacestode antigens,
EmG11 2 and Em2, which both were affinity purified
and which are functionally identical, and the recom-
binant antigen II/3-10, which is functionally different
from EmG11 and Em22) which are highly specific for
E. multilocularis. A mixture of the Em2 and the II/3-10
antigens is used in the commercial Em2 plus ELISA. a,3
A strong positive result was obtained in the ELISA
with the II/3-10 antigen, and weakly positive results
were seen with the EmG11 antigen as well as with the
Em2 plus-ELISA.
To exclude a concomitant intestinal infection with
adult tapeworms of the same species, several fecal
samples were examined within 10 days by a com-
bined sedimentation/flotation method for cestode eggs
and by an ELISA for specific coproantigens of E.
multilocularis. 4 All tests were negative for intestinal
parasites. These negative results indicated that the
dog did not carry intestinal E. multilocularis stages at
the time of examination. However, a previous infec-
tion and thus a potential zoonotic risk for humans
could not be ruled out. Therefore, several humans
who had been in contact with the dog were tested by a
serological surveillance program recommended by the
Swiss National Center for Echinococcosis; 5 no posi-
tive reactions were found.
Postoperative chemotherapy similar to a protocol
used in human medicine was begun because of the
tumor-like proliferation and the well-known potential
Alveolar Echinococcosis 311
Figure 6—Serum electrophoresis after three months of treat-
ment. Hypergammaglobulinemia has disappeared almost com-
pletely (compare to Figure 3).
for metastasis formation of E. multilocularis meta-
cestodes. 6,7 Albendazole b (10 mg/kg body weight,
once daily with food) was administered. The treat-
ment consisted of alternating cycles of four weeks’
treatment followed by two weeks without medica-
tion. 7 To exclude any undetected concomitant infec-
tion with intestinal stages of E. multilocularis, the
dog was treated orally with praziquantelc (10 mg/kg
body weight [double the therapeutic dose]). This
medication was repeated once after two weeks. An
intensive follow-up monitoring program was estab-
lished. Every three months, a CBC, serum biochemis-
try profile, serum electrophoresis, ultrasonographic
examination of the liver, and serological tests for E.
multilocularis were performed. To date (May 1997),
the dog has been treated with 15 cycles of chemo-
therapy during a follow-up period of 21 months.
The dog has been clinically normal and in good
general condition. Three months after surgery, the
hyperglobulinemia had resolved and the serum elec-
trophoresis had a normal distribution pattern [Figure
6]. Repeated biochemical profile results remained in
the normal reference range, including hepatic enzyme
312 JOURNAL of the American Animal Hospital Association
Table
Table—Serial enzyme-linked immunosorbent assay (ELISA)
results with various antigens specific for Echinococcus
multilocularis before and after surgery. For each serum sample,
relative optical densities (ODs) were calculated by subtraction
of antigen-dependent cut-off values. Values above zero are
therefore considered positive. For each antigen, a cut-off value
was determined as the mean OD plus three standard deviations
of 13 clinically normal control dogs.
activities. Ultrasonographic evaluation of the liver
revealed a displacement of the gall bladder to the left,
resulting from the loss of the two resected liver lobes.
The remaining liver tissue appeared to be normal in
texture and echogenicity. Serum antibody levels were
less markedly positive 46 days after surgery in all
three serological tests. After 109 days, only the II/3-
10 ELISA showed low specific reaction which con-
verted to negative in the following test dates on days
221 and 326 after surgery [see Table].
After almost two years of treatment, the dog did
not show any signs of recurrence of the disease or
side effects from the medication. The dog continues
to be treated with albendazole as described previously.
Discussion
Echinococcus multilocularis is a cestode for which
the natural life cycle typically involves rodents as
intermediate hosts and foxes as definitive hosts. In
some geographic regions, other carnivores (e.g., coy-
otes, wolves, domestic dogs or cats) may act as final
hosts. 8 Intermediate hosts ingest parasite eggs (which
have been excreted by the definitive hosts) from which
metacestodes develop. Definitive hosts acquire the
infection by the ingestion of intermediate host ani-
mals infected with the larval stage (i.e., metacestode)
containing protoscoleces of the parasite. Occasion-
ally, eggs from E. multilocularis may be ingested by
humans or animals which do not play an epidemio-
July/August 1998, Vol. 34
logical role in the parasite’s life cycle. They are de-
nominated as accidental hosts which may suffer from
AE, the disease caused by the proliferation of the
metacestode stage of E. multilocularis. Dogs may
acquire the E. multilocularis infection as final hosts
or as accidental hosts. Therefore, epidemiological and
clinical aspects of this dual role will be discussed.
The geographic distribution of E. multilocularis is
restricted to the northern hemisphere and includes
parts of central and eastern Europe, Asia, and North
America. 9,10 In European countries and regions, the
average prevalence rates of intestinal E. multilocularis
infection in foxes range from less than 1% to greater
than 40%.10 In an endemic part of eastern Switzer-
land, with prevalence rates of E. multilocularis infec-
tion in foxes being greater than 30%, only 0.3% of
661 dogs and 0.2% of 452 cats were infected with
intestinal stages of the parasite.10 The dog presented
in this report originated from a highly endemic area
with an average prevalence rate of 44% for E.
multilocularis infection in the fox population; this is
one of the unusual cases in which the dog is an acci-
dental host for the metacestode stage. Three similar
cases in dogs had been observed previously in Switzer-
land, and two cases have been reported from Germany,
but they were diagnosed postmortem or euthanized
immediately after diagnosis without treatment.10,11
The eggs of E. multilocularis may reach the dog’s
intestine from the environment after peroral ingestion
or they may be released within the dog’s own intes-
tine if the animal is infected with adult stages of the
parasite. It has been demonstrated for Taenia hyda-
tigena and other Taenia species that oncospheres may
hatch from some eggs which are released into the
small intestine.12 Furthermore, oncosphere-specific
serum antibodies have been detected in dogs two
months after experimental infection with Echinococ-
cus granulosus (E. granulosus), which suggests that
oncospheres penetrated the mucosa and stimulated
the immune system.13 Details on this early phase of
infection still are unknown. A similar mode of infec-
tion is assumed for E. multilocularis, resulting in
migration of hatched oncospheres from the mucosa to
the liver with subsequent development to the meta-
cestode stage. However, it appears that such infec-
tions of dogs resulting in AE are extraordinary events.
Intestinal stages of E. multilocularis normally do
not cause clinical signs in the definitive hosts, even if
a large number (greater than 10,000 per animal) of
parasites are present. Up until now, a specific diagno-
sis in the living animal was very difficult to make, as
the small proglottids of E. multilocularis excreted in
the feces often were overlooked and the eggs of the
parasite could not be differentiated microscopically
from those of Taenia spp., E. granulosus, or Multi-
ceps spp. By the use of newly developed techniques
July/August 1998, Vol. 34
such as coproantigen detection by sandwich ELISA
or characterization of E. multilocularis eggs by polym-
erase chain reaction (PCR), reliable diagnosis of the
intestinal infection is now possible.4,14 In contrast to
the intestinal stages of E. multilocularis, the meta-
cestode can be highly pathogenic in intermediate and
accidental hosts. In humans, it may cause severe AE
which is lethal in more than 50% to nearly 100% of
untreated patients. 6 The location of metacestodes in
humans as well as in other accidental hosts and natu-
ral intermediate hosts is almost exclusively the liver.
This stage of the parasite is characterized by tumor-
like proliferation and by the potential of metastasis
formation in adjacent or distant organs. 6
The initial clinical symptoms of hepatic AE in
humans are epigastric pain, jaundice, or both; but
these occur in only about one-third of patients. Rou-
tine laboratory tests normally do not yield specific
findings. Jaundice might be seen in patients with in-
trahepatic bile duct compression or obstruction. Hy-
perglobulinemia is present in most patients with AE.6
Diagnosis of AE in humans is based on clinical find-
ings and morphological features revealed by imaging
techniques such as radiography, ultrasonography,
computerized tomography, or magnetic resonance im-
aging. Immunodiagnostic tests are important for the
etiologic diagnosis of AE. The test sensitivity is about
95% to 100%, and specificity also is high if purified
and specific antigens are used. 3,15
The choice of treatment modalities depends on the
stage of the disease at the time of diagnosis. Surgical
resection of the involved liver segment and of
metacestode lesions from other affected organs is in-
dicated in all operable cases. 6,7 Due to the tumor-like
proliferation, even after macroscopically radical sur-
gery, it is difficult or impossible to predict whether or
not surgery successfully removed all metacestode tis-
sue. Therefore, postoperative chemotherapy with
mebendazole or albendazole for at least two years
after radical surgery is recommended with careful
monitoring of the patient over a minimum of 10 years
for possible recurrence. 6,7 After nonradical resection,
or if inoperable, patients require continuous chemo-
therapy for many years as drug treatment normally
does not kill the parasite but inhibits its proliferation.
Alveolar echinococcosis in the dog presented here
exhibited several common features with human AE,
notably very similar morphological findings in ab-
dominal images, hypergammaglobulinemia, and
pathomorphological lesions. The lack of cholestatic
jaundice or other obvious signs of illness most likely
contributed to this dog’s advanced stage at presenta-
tion. Two cases of AE described in Germany were
presented for clinical examination for suspected pyo-
metra and abdominal tumor, respectively. Exploratory
laparotomy revealed large metacestode masses in the
Alveolar Echinococcosis 313
liver of one dog and in the omentum exclusively in
the other dog. 11 In the latter case, the liver apparently
was not involved; however, liver lesions may be small
and grossly undetectable in the living animal. In the
case reported here, parasite masses had infiltrated
larger parts of the liver and also the peritoneal cavity.
Recommendations for treatment of dogs carrying
metacestodes of E. multilocularis could not be found
in the veterinary literature. Therefore, a schedule from
human medicine was adopted for the treatment of this
case. Surgical resection of all macroscopically abnor-
mal tissue and postoperative chemotherapy with
albendazole was established. The dog has been in
clinical remission for 21 months postoperatively.
Treatment with albendazole is recommended indefi-
nitely in this dog. Postoperative chemotherapy is es-
sential for the treatment of parasite tissue not removed
at the time of surgery. In human patients, recurrences
of AE were observed in 37% of 19 cases reported
after discontinuation of long-term (more than two
years) therapy with mebendazole.6
Conclusion
Surgical resection followed by postoperative chemo-
therapy with albendazole resulted in long-term clini-
cal remission of AE in a dog. In endemic areas, AE
should be included in the differential diagnosis of
hepatic masses, especially if concomitant hyperglobu-
linemia is present.
a
Em2 plus ELISA; Bordier Affinity Products, CH-1023 Crissier, Switzer-
land
b
Valbazen; SmithKline Beecham Animal Health, Great Britain
c
Droncit; Bayer AG, Leverkusen, Germany
References
1. Chitwood M, Lichtenfels JR. Identification of parasitic metazoa in
tissue sections. Experimental Parasitol 1972;32:407–519.
2. Deplazes P, Gottstein B. A monoclonal antibody against Echinococcus
multilocularis Em2 antigen. Parasitol 1991;103:41–9.
3. Gottstein B, Jacquier P, Bresson-Hadni S, Eckert J. Improved primary
immunodiagnosis of alveolar echinococcosis in humans by an enzyme-
linked immunosorbent assay using the Em2 plus antigen. J Clin
Microbiol 1993;31:373–6.
4. Deplazes P, Eckert J. Diagnosis of the Echinococcus multilocularis
infection in foxes and other final hosts. Appl Parasitol 1996;37:245–52.
5. Eckert J, Ewald D, Siegenthaler M, Brossard M, Zanoni RG, Kappeler A.
Der “Kleine Fuchsbandwurm” (Echinococcus multilocularis) in der
Schweiz: Epidemiologische Situation bei Füchsen und Bedeutung für
den menschen. Bulletin, Bundesamt fuer Gesundheitswesen, Bern, Nr 25
1993;S:468–76.
6. Ammann RW, Eckert J. Cestodes. Echinococcus. In: Weinstock JV, ed.
Parasitic diseases of the liver and intestines. Gastroent Clin N Am,
1996:655–89.
7. World Health Organization guidelines for treatment of cystic and alveo-
lar echinococcosis. WHO informal working group on echinococcosis.
Bull Wrld Hlth Org 1996;74:231–42.
8. Rausch RL. Life cycle patterns and geographic distribution of Echino-
coccus species. In: Thompson RCA, Lymbery AJ, eds. Echinococcus
and hydatid disease. Oxon: CAB International, 1995:88–134.
(Continued on next page)
314 JOURNAL of the American Animal Hospital Association
References (cont’d)
9. Schantz PM, Chai J, Craig PS, et al. Epidemiology and control of hydatid
disease. In: Thompson RCA, Lymbery AJ, eds. Echinococcus and hy-
datid disease. Oxon: CAB International, 1995:233–331.
10. Eckert J. Der “gefährliche Fuchsbandwurm” (Echinococcus
multilocularis) und die alveoläre Echinokokkose des Menschen in
Mitteleuropa. Berl Münch Tierärztl Wschr 1996;109:202–10.
11. Geisel O, Barutzki D, Minkus G, Hermanns W, Löscher T. Hunde als
Finnenträger (Intermediärwirt) von Echinococcus multilocularis.
Kleintierpraxis 1990;35:275–80.
July/August 1998, Vol. 34
12. Coman BJ, Rickard MD. The location of Taenia pisiformis, Taenia ovis
and Taenia hydatigena in the gut of the dog and its effect on net
environmental contamination with ova. Z Parasitenkd 1975;47:237–48.
13. Gasser RB, Lightowlers MW, Obendorf DL, Jenkins DJ, Rickard MD.
Evaluation of a serological test system for the diagnosis of natural
Echinococcus granulosus infection in dogs using E. granulosus
protoscolex and oncosphere antigens. Aust Vet J 1988;65:369–73.
14. Mathis A, Deplazes P, Eckert J. An improved test system for PCR-based
specific detection of Echinococcus multilocularis eggs. J Helminthol
1996;70:219–22.
15. Gottstein B. Echinococcus multilocularis infection: immunology and
immunodiagnosis. Advances in Parasitology 1992;31:321–80.
 Uroperitoneum in Cats:
26 Cases (1986–1995)
Uroperitoneum (UP) was diagnosed in 26 cats. Trauma was the most common
cause (84.6%), including blunt abdominal trauma (59.1%), urethral catheterization
(31.8%), and bladder expression (9.1%). The bladder was the most frequent site of
urine leakage following blunt abdominal trauma (84.6%), while the urethra was the
most common site following catheterization (71.4%). Common historical complaints
were anuria (53.8%) and vomiting (50%).
On physical examination, the bladders were palpable in nine (69%) of 13 cases;
four of the nine had ruptured bladders. The ability to urinate did not exclude a
diagnosis of UP since four noncatheterized cases reportedly urinated. Twenty-five
cases were azotemic on presentation. The creatinine or potassium (K+)
concentration in the serum compared to that in the peritoneal effusion (mean ratio,
1:2 and 1:1.9, respectively) was a useful indicator for UP. When performed, positive
contrast radiography was diagnostic. Drainage of urine from the peritoneal cavity
appeared to improve patient stabilization. Morbidity and mortality depended largely
on the severity of associated injuries. J Am Anim Hosp Assoc 1998;34:315–24.

Marcel Aumann, Dr. med. vet. Introduction

Leila T. Worth, VMD, PhD
Kenneth J. Drobatz, DVM
RS
From Veterinary Centers of America,
Veterinary Referral Associates (Aumann),
15021 Dufief Mill Road,
Gaithersburg, Maryland 20878 and the
Department of Clinical Studies
(Worth, Drobatz),
School of Veterinary Medicine,
University of Pennsylvania,
Philadelphia, Pennsylvania 19104–6010.
Uroperitoneum (UP) is defined as an accumulation of urine in the
peritoneal cavity following leakage from the kidneys, ureter, bladder,
or urethra. The etiology of UP differs with species, gender, and age.1
As in humans, UP in dogs and cats most commonly results from
trauma to the abdomen or pelvis. 2–8 Between 39% and 46.2% of dogs
with pelvic fractures had associated urinary tract injuries. 5,6 Urinary
tract injuries were diagnosed in only 0.5% of cats with pelvic frac-
tures. 7 Less common etiologies of UP include transitional cell carci-
noma of the bladder in dogs 9 and urethral calculi in cats. 10
A mortality rate of 11% to 44% is reported in humans with UP3 and
a mortality rate of 42.3% is reported in dogs with UP. 5 Although
associated injuries are responsible for most deaths, a delay in diagno-
sis of UP increases mortality rate.5,11 The diagnosis of UP represents
a challenge, 5 but a tentative diagnosis often can be made on the basis
of history, physical examination, clinicopathological findings, and
abdominal radiography. 6 However, radiographic contrast studies, ex-
ploratory surgery, or necropsy are necessary to confirm the diagnosis
and locate the source of urine leakage. 5,6
Treatment for UP depends largely on the etiology as well as the
extent and location of urine leakage. 6,10,12 Although surgical treat-
ment is most common, 4,12 conservative therapy has been reported for
ruptured bladder and urethral tears in humans and animals.1,3,10,13,14
Despite the reports of UP following abdominal trauma 7 and ure-
thral calculi 10 in cats, little is known about this condition in cats. The
goals of this retrospective study were to identify typical clinical
signs, clinicopathological findings, etiologies, and methods of diag-
nosis and to assess treatment and outcome in cats with UP.

JOURNAL of the American Animal Hospital Association 315

316 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

The causes for UP were divided into trauma

Table 1 (including blunt abdominal trauma [i.e., hit by car,
Historical Complaints in 26 Cats unknown trauma]), catheterization, and bladder ex-
with Uroperitoneum pression; urethral obstruction; and neoplasia. If avail-
able, the site of urine leakage was recorded and
correlated with the etiology of UP.
Historical Complaint No. of Cats
Therapy and case management were at the discre-
Anuria 14 tion of the clinician. Drugs, fluid therapy, peritoneal
Vomiting 13 drainage or dialysis, urinary catheterization, and sur-
Lethargy 12 gery were recorded for each case. Urine output was
Trauma 10 recorded in each case that had an indwelling urinary
Anorexia 10 catheter placed. The ability to urinate was determined
Dysuria 8 from the medical record progress notes for the re-
Lameness 4 maining cases. Surgical findings were compared to
Pain 3 those obtained by radiology, at necropsy, or both.
Shock 3
Outcomes were recorded and, where applicable, gross
pathological and histological findings were reported.
Coma 2
The Mann-Whitney test was used to describe dif-
Diarrhea 2
ferences in median hospitalization time for cases with
Hematuria 1 UP with or without associated injuries. The chi-square
Hematemesis 1 (χ 2) test was used to assess the differences between
Renal calculi 1 males and females with UP or bladder rupture, re-
Urethral tear 1 spectively. A p of less than 0.05 was considered sig-
Polydipsia 1 nificant. Analyses were performed using a statistical
software program. b Data is presented as mean±
standard deviation (SD) or median.

Materials and Methods
Medical records of all cats diagnosed with UP at the
Veterinary Hospital of the University of Pennsylva-
nia between April 1986 and December 1995 were
reviewed. Cases were included in the study if the
diagnosis was confirmed by radiographic contrast
study of the urinary tract, exploratory surgery, or
necropsy, or a combination.
The medical records were reviewed for signalment,
historical and clinical signs, and clinicopathological
values at admission including packed cell volume
(PCV); white blood cell (WBC) count; serum concen-
trations of urea nitrogen, a creatinine, phosphorus, so-
dium (Na +), potassium (K +), chloride (Cl -), and total
protein; and urinalysis results. When available, se-
rum concentrations of urea nitrogen and creatinine
that were collected after peritoneal drainage or dialy-
sis and again after surgery or before discharge also
were reviewed. The macroscopic appearance and cy-
tology of the peritoneal effusion were evaluated. The
concentrations of total solids, urea nitrogen, creati-
nine, and K + in the peritoneal effusion also were
evaluated. Values were compared to those of serum.
The sources of the samples and the bacterial isolates
were recorded in those cases that had microbiological
cultures performed. Radiographic findings, including
contrast studies, were reviewed by a radiologist
(Worth).
Results
Thirty-four cases were diagnosed with UP during the
study period. Eight of the 34 cases were excluded
because the diagnosis was not confirmed via radio-
graphic contrast study, exploratory surgery, or
necropsy, leaving 26 cases for evaluation. The num-
ber of cases for each parameter assessed was variable
because of differences in case management. A defini-
tive diagnosis of urinary tract leakage was made in 12
(46.2%) cases through radiographic contrast studies,
in 12 (46.2%) cases at surgery, and in two (7.6%)
cases at necropsy. The median time period from ad-
mission to final diagnosis was 13 hours (range, one to
62 hrs; n=17).
Breeds included domestic shorthair (n=23), domes-
tic longhair (n=1), Siamese (n=1), and Russian blue
(n=1). There were 13 castrated males, eight intact
males, three spayed females, and two intact females.
Males were diagnosed with UP significantly more
often than females (p less than 0.02). Median age was
2.1 years (range, five months to 17.5 years; n=25).
Historical complaints are summarized in Table 1. Me-
dian duration of illness prior to presentation was 24
hours (range, one to 240 hrs; n=16).
Upon physical examination, median rectal tempera-
ture on admission was 36.2˚ C (range, 33.8˚ C to 39.7˚ C;
n=22). Five of 23 cases were bradycardic (heart rate
less than 140 beats per min), three of which were
hyperkalemic (serum K +, greater than 5.1 mEq/L).
July/August 1998, Vol. 34 Uroperitoneum 317

Blood urea nitrogen (BUN) and creatinine concen-

Table 2 trations were recorded in 17 cases after surgery or
Physical Examination Findings before discharge. Three cases remained azotemic af-
in 26 Cats with Uroperitoneum ter surgery, two of which had the highest creatinine
values (22.1 mg/dl and 20.0 mg/dl, respectively) on
presentation. The time required for resolution of
Physical Examination Findings No. of Cats
azotemia tended to be longer in cases with multiple
Dehydration 21 injuries unrelated to the urinary tract (median, 58 hrs;
Altered mentation (i.e., depressed, 18 range, nine to 96 hrs; n=7) compared to cases with
stuporous, comatose) urinary tract injuries only (median, 16.5 hrs; range,
Hypothermia (<37.8˚ C) 13 nine to 72 hrs; n=6).
Tachypnea (>40 breaths/min) 12 Gross hematuria was noted in six of the 26 cases.
Poor perfusion 11 Urinalysis was recorded in seven cases, and findings
Distended abdomen 9 included proteinuria (n=7), hematuria (n=7), glucos-
Bladder palpable 9 uria (n=1), and bilirubinuria (n=1). Urine specific
Pain on abdominal palpation 8 gravity ranged from 1.015 to 1.024. Urine sediment
Signs of recent trauma (excluding 6 analysis was evaluated in three cases and was charac-
pelvic fractures) terized by numerous red blood cells (RBCs) (n=2)
Bradycardia (<140 beats/min) 5 and tubular casts (n=1).
Bladder not palpable 4 Abdominocentesis was performed in 14 cases, and
Fluid wave on abdominal palpation 3 fluid was obtained in 13 cases. The fluid was de-
Pelvic fractures 3
scribed as serosanguineous in all samples for which it
was recorded (n=8). Values for total solids (TS) (n=4)
Tachycardia (>220 beats/min) 2
were less than 2.5 g/dl in three cases and greater than
Heart murmur 1
2.5 g/dl in one case. In the latter case, toxic and
degenerative neutrophils with intracellular cocci and
Two cases were tachycardic (heart rate greater than rods were seen upon cytology of the fluid. The mean
220 beats per min). Abdomens were distended in nine creatinine concentration of the abdominal fluid±SD
cases, and fluid waves were palpable in three cases. was 12.5±4.9 mg/dl (n=5), and the mean K+ concen-
Eight cases were painful on abdominal palpation. tration±SD was 9.3±7.4 mEq/L (n=5). In four cases,
Signs of recent trauma, most commonly associated the mean serum creatinine-to-abdominal fluid creati-
with the caudal abdomen and rear limbs, were noted nine ratio was 1:2 (range, 1:1.1 to 1:4.1), and the
in six of the 26 cases, three of which had pelvic corresponding mean K + ratio was 1:1.9 (range, 1:1.2
fractures. Bladders were palpable in nine of 13 cases, to 1:2.4). Both the creatinine ratio and the K + ratio
not palpable in four of these 13 cases, and not as- were reversed in the remaining case (1:0.8 and 1:0.9,
sessed in the remaining 13 cases. Other abnormalities respectively). Abdominal fluid urea nitrogen concen-
detected on physical examination are summarized in trations a (n=5) were higher than the serum concentra-
Table 2. tions in four cases and were equal to the serum
Clinicopathological findings are summarized in concentration in the remaining case.
Table 3. All except one case were azotemic on admis- Three of five aerobic bacteriological cultures ob-
sion. Peritoneal drainage only was utilized in four tained from the peritoneum (n=4) and the bladder (n=1)
cases, and serum creatinine decreased from greater at surgery were positive. Organisms isolated included
than 14 mg/dl to 10.4 mg/dl in one case, increased Enterococcus spp. (n=3), Staphylococcus epidermidis
from 3.0 mg/dl to 3.6 mg/dl in another case, and was (n=1), and alpha-Streptococcus (n=1).
not assessed in the remaining two cases. Serum crea- Table 4 summarizes the abdominal radiographic
tinine decreased from 13 mg/dl to 10.4 mg/dl, 22.1 findings. Radiographic contrast studies were per-
mg/dl to 7.7 mg/dl, and 5.1 mg/dl to 0.6 mg/dl, re- formed on 12 cases and included eight positive con-
spectively, in the three cases in which peritoneal di- trast cystograms, seven retrograde urethrograms, and
alysis was performed. Thirteen of 24 cases were three excretory urograms. When performed, radio-
hyperkalemic (serum K +, greater than 5.1 mEq/L), graphic contrast studies were diagnostic in all cases.
and one case was hypokalemic (serum K +, less than Cystograms demonstrated ruptured bladders in five
3.5 mEq/L) on presentation. Thirteen of 15 cases were cases, while urethrograms identified five urethral tears
hyperphosphatemic (phosphorus, greater than 6.0 mg/ and one bladder avulsion. An excretory urogram re-
dl). Hyperkalemia and hyperphosphatemia resolved vealed urine leakage in a case with chronic renal
following surgery and before discharge in those cases failure and UP postnephrotomy, but it failed to differ-
for which K + and phosphorus levels were recorded. entiate between ureteral and bladder leakage.
318 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

Table 3
Clinicopathological Findings in 26 Cats with Uroperitoneum

Percentage (Number Percentage (Number

of Cats Below of Cats Above Number Reference
Mean±SD* Range Reference Range) Reference Range) of Cats Range
Packed cell volume (%) 41.6±10.3 15.0–56.0 3.8 (n=1) 30.8 (n=8) 26 24–45
Total solids (g/dl) 8.1±1.3 5.5–10.5 — 80.8 (n=21) 26 5.5–7.1
White blood cell 16,980±7,800 4,200–29,300 6.3 (n=1) 31.3 (n=5) 16 5,500–19,500
count (cells/µl)
Sodium (mEq/L) 147.3±9.5 125.0–170.0 45.8 (n=11) 12.5 (n=3) 24 148–157
Chloride (mEq/L) 116.1±7.1 104.0–125.0 50.0 (n=6) 8.3 (n=1) 12 115–128
Potassium (mEq/L)
Admission 5.8±2.1 3.2–9.8 4.2 (n=1) 54.2 (n=13) 24 3.5–5.1
Abdominal fluid 9.3±7.4 4.1–22.2 — — 5
Phosphorus (mg/dl) 10.4±5.6 3.6–26.5 — 86.7 (n=13) 15 2.5–6.0
Urea nitrogen (mg/dl)
Admission 115.3±77.1 19.0–318.0 — 93.3 (n=14) 15 15–29
Postsurgery/ 20.3±16.0 5.0–56.0 — — 14 —
predischarge
Creatinine (mg/dl)
Admission 8.0±5.7 1.0–22.1 — 95 (n=19) 20 0.5–2.0
Abdominal fluid 12.5±4.9 5.5–15.6 — — 5 —
Postdrainage/ 6.6±4.4 0.6–10.6 — — 5 —
dialysis
Postsurgery/ 1.8±2.2 0.6–9.5 — — 15 —
predischarge

* SD=standard deviation

Exploratory laparotomies were performed in 19
cases. Urinary tract defects were diagnosed before
surgery using contrast radiography or were suspected
based on clinical signs and clinicopathological and
radiographic findings in 17 cases. Ruptured bladders
were incidental findings in two cases that went to
surgery for confirmed septic peritonitis and an ab-
dominal wall hernia with possible bowel rupture, re-
spectively. Urological abnormalities noted at surgery
included ruptured bladder (n=14), urethral tear (n=3),
avulsion of the ureter (n=1), urethral obstruction
(n=1), uroretroperitoneum (n=1), bilateral subcapsu-
lar renal hematoma (n=1), bladder tumor (n=1), and
partial-thickness bladder tear (n=1). Locations of the
bladder ruptures were recorded in eight cases and
occurred at the apex (n=3), at the trigone (n=2), dor-
sally (n=2), and ventrally (n=1). Multiple urological
abnormalities were present in one case. Hyperemic
peritoneum was noted in two cases, one of which had
septic peritonitis.
Necropsy (n=5) findings pertaining to the urinary
tract included hemorrhagic cystitis (n=3), acute blad-
der rupture (n=2), chronic bladder rupture (n=1),
chronic cystitis (n=1), and avulsion of the urethra
(n=1). More than one urological abnormality was
present in one case. Other findings were peritoneal
fluid accumulation (n=2) and acute peritonitis (n=1).
Necropsies were performed on three of the five cases
after cardiac arrest postsurgery.
Table 5 summarizes the underlying causes for UP
and the sites of urine leakage. Causes for UP were
trauma (n=22), including blunt abdominal trauma
(n=13), catheterization (n=7), and bladder expression
(n=2); urethral obstruction (n=2); urinary bladder neo-
plasia (n=1); and nephrotomy (n=1). The bladder was
the most common site of urine leakage following
blunt abdominal trauma (n=11), and the urethra was
the most common site following catheterization (n=5).
All cases that sustained bladder or urethral trauma
following catheterization were catheterized because
of urethral obstruction. There was no significant dif-
ference between the number of males and females
with bladder rupture.
Definitive treatment was initiated in 19 cases.
Treatment included surgical repair (n=18) and con-
servative therapy (n=1). Conservative therapy was
utilized in one case with a urethral tear because of a
minor urological defect and financial limitations.
Medical management included intravenous admin-
istration of a balanced electrolyte solution (n=24),
whole blood (n=5), antibiotics (n=22), corticoster-
oids (n=7), opiate analgesics (n=5), low-dose infu-
July/August 1998, Vol. 34 Uroperitoneum 319

Table 4
Radiographic Findings in 26 Cats with Uroperitoneum

No. of
Radiographic Study Radiographic Findings Cats
Survey radiographs (n=18)* Decreased intraperitoneal detail 18
Bladder not visible 14
Decreased retroperitoneal detail 7
Pelvic fractures 4
Kidneys not visible 2
Abdominal hernia 1
Cranially displaced bladder 1
Renal calculi 1
Small/irregular kidneys 1
Free intra-abdominal air 1

Cystogram (n=8) Ruptured bladder 5

Retrograde urethrogram (n=7) Urethral tear 5

Avulsion of the urethra 1

Excretory urogram (n=3) Cranially displaced bladder 1

Small kidneys 1
Distended renal pelvis 1
Intraperitoneal contrast material 1

* The number in the parentheses indicates the number of cats in which the radiographic study was performed

Table 5
Etiology, Sex Distribution, Site of Urine Leakage, and Outcome in 26 Cats with Uroperitoneum

No. Females/
Etiology of Cats Males Site of Urine Leakage Outcome
Trauma 22 3/19 Bladder (n=15); urethra (n=7); Survived (n=15);
ureter (n=1) euthanized/died (n=7)
Blunt abdominal 13 3/10 Bladder (n=11); urethra (n=2); Survived (n=10);
trauma ureter (n=1) euthanized/died (n=3)
Catheterization 7 0/7 Bladder (n=2); urethra (n=5) Survived (n=4);
euthanized (n=3)
Bladder expression 2 0/2 Bladder (n=2) Survived (n=1);
euthanized (n=1)

Urethral obstruction 2 0/2 Bladder (n=2) Survived (n=1); died (n=1)

Bladder neoplasia 1 1/0 Bladder (n=1) Euthanized (n=1)

Nephrotomy 1 1/0 Undetermined Euthanized (n=1)

Total 26 5/21 Bladder (n=18); urethra (n=7); Survived (n=16);

ureter (n=1) euthanized/died (n=10)

sion of dopamine (n=4), furosemide (n=4), systemic
vasodilators (n=2), and mannitol (n=1). Cases with
hyperkalemia received dextrose and regular insulin
intravenously (n=5), calcium gluconate (n=2), and
sodium bicarbonate (n=2).
Urinary catheters were placed in 14 cases for vari-
ous reasons, including relief of a urethral obstruction
(n=7), assessment of urine output (n=6), and for the
management of a urethral tear (n=1). All of the uri-
nary catheters were placed prior to surgery and re-
320 JOURNAL of the American Animal Hospital Association
mained in place after surgery in eight cases to pro-
mote healing of urethral tears or to assess urine out-
put. Urine output was described subjectively as
adequate in eight catheterized and noncatheterized
cases, and output (range, 3.9 to 19 ml/kg per hr) was
recorded in four cases. Three cases with urinary cath-
eters remained anuric. Urine output was not assessed
in 11 cases.
Peritoneal drainage was performed in four cases,
and peritoneal dialysis was performed in three cases
for a duration of five-to-16 hours. Peritoneal drainage
was performed in the conservatively treated case to
promote resolution of azotemia. In the remaining
cases (n=6), peritoneal drainage/dialysis was insti-
tuted as a means of presurgical stabilization.
Surgical treatment for ruptured bladder consisted
of routine closure of the defect (n=8). Temporary
cystostomies were performed in four cases with ure-
thral tears or disruption of the urethra before defini-
tive surgical repairs through prepubic urethrostomies
(n=3) or routine closure of the urethra (n=1). A ne-
phrectomy was performed in the case with the avulsed
ureter.
Seven of 26 cases with UP were euthanized before
definitive treatment could be initiated, because of
financial concerns (n=4), severity of sustained inju-
ries (n=1), or severity of medical problems including
the development of acute renal failure postnephrot-
omy (n=1) and an unresectable bladder tumor found
at surgery (n=1). Three cases suffered cardiac arrest
seven-to-28 hours postsurgery; endomyocarditis was
diagnosed in one case on necropsy. No underlying
cause could be identified in the other two cases. The
remaining 16 cases were discharged. Median hospi-
talization time for cases with multiple injuries unre-
lated to the urinary tract (231 hrs; range, 147 to 504
hrs; n=6) was significantly longer (p less than 0.005)
than for cases with urinary tract abnormalities only
(92 hrs; range, 60 to 360 hrs; n=10). A correlation
between the time of urinary tract injury to presenta-
tion and outcome could not be established because of
the small number of cases (n=5) for which the time of
onset of clinical signs related to UP could be deter-
mined with certainty.
Discussion
Uroperitoneum has been described previously in cats
as a result of pelvic fractures 7 and urethral calculi. 10
Although the overall incidence of UP was not re-
ported, urinary tract injuries were diagnosed in 0.5%
of cats with pelvic fractures. 7 In the authors’ study,
UP accounted for 0.1% of the hospital feline popula-
tion. Trauma was the most common cause for UP in
cats evaluated in this study and was reported previ-
ously as being the most common cause for UP in
humans 13 and dogs. 5,6 Trauma included blunt abdomi-
July/August 1998, Vol. 34
nal trauma, traumatic catheterization of cats with ure-
thral obstruction, and bladder expression. The blad-
der was the most frequent site of urine leakage
following blunt abdominal trauma. Blunt abdominal
trauma was reported to be the most common cause for
bladder rupture in humans 13 and dogs.5,6 Urethral tears
are uncommon in small animals and may result from
pelvic fractures, urethral obstruction, or improper
catheterization. 10 In five of seven cats, urethral tears
resulted from traumatic catheterization for urethral
obstruction. One case in this study had a bladder
tumor leading to rupture. To the authors’ knowledge,
bladder tumor resulting in UP has not been reported
previously in cats, although it has been described in
the dog. 9
Males were diagnosed with UP significantly (p
less than 0.02) more often than females. Traumatic
bladder rupture is reported to occur more frequently
in male dogs because of the limited ability of the
long, narrow urethra to dilate rapidly in response to
increased intravesicular pressures. 10 Although a simi-
lar mechanism seems likely in cats, there was no
significant difference between the frequency of blad-
der rupture in males and the frequency in females in
this study. Feline lower urinary tract disease (FLUTD)
was diagnosed in 52.4% of male cats with UP. It was
the most common cause associated with urethral tears
and the second most common cause associated with
bladder rupture, both of which were induced iatro-
genically in the majority of these cases. Urethral ob-
struction with FLUTD occurs more frequently in male
cats 10 and can lead to bladder distention and rupture.
Catheterization of the inflamed urethra in cats with
FLUTD also could result in urethral tears.
Median duration of illness prior to presentation
was 24 hours (range, one to 240 hrs). Death might
occur as early as 24 hours after rupture of the bladder
in clinical cases 10 and has been reported to occur
within 47 to 90 hours in dogs with experimentally
induced bladder rupture. 5
Anuria and dysuria were by far the most common
historical complaints (in 84.6% of cases). Almost 50%
of these cats were males with urethral obstruction.
Anuria and dysuria were associated consistently with
urinary tract trauma in dogs with pelvic fractures 6
and were reported in almost 50% of the cases in
which urine leakage occurred from sites other than
the urethra in the present study. Urine output in cath-
eterized and noncatheterized cats was adequate in
46.2% of the cases, and only 21.4% of the cases
remained anuric after catheterization. The authors’
findings confirm reports in dogs and other species
that the ability to urinate does not exclude a diagnosis
of urinary tract rupture. 1,5,6
Depressed mentation was the most common physi-
cal examination finding and might be attributable to
July/August 1998, Vol. 34
uremia, dehydration, electrolyte and acid/base abnor-
malities, pain, or trauma. Median rectal temperature
was 36.2˚ C. Uremia can result in hypothermia 10 as
well as decreased rectal perfusion. The median heart
rate was 157 beats per minute, and bradycardia oc-
curred in a minority of the cats. Hyperkalemia (serum
K + range, 5.15 to 9.84 mEq/L), which was noted in
50% of the cases, was the most likely cause for the
bradycardia; however, hypothermia and acid/base dis-
turbances could have been contributing factors. Physi-
cal examination findings suggestive of urinary tract
injury in this study included distended abdomen, ab-
dominal pain, fluid wave on abdominal palpation,
hematuria, and lack of a palpable bladder. These find-
ings, however, are not specific for urinary tract in-
jury, nor does their absence rule out urinary tract
leakage. 6 The incidence of clinically undetected uri-
nary tract trauma in this study was 15.4%, and it had
been reported to be as high as 20% to 50% in dogs
with pelvic fractures. 6 A palpable bladder does not
rule out bladder rupture, because the bladder was
palpable in 20% of the cats with ruptured bladders.
Clinical and clinicopathological signs (i.e., dry
mucous membranes, decreased skin turgor, increased
PCV and TS) of dehydration were noted in the major-
ity of the cats in this study. Dehydration and hemo-
concentration can be related to decreased fluid intake
and excess fluid loss due to vomiting. The osmotic
effect of the hypertonic urine, possibly together with
peritonitis, leads to marked fluid shifts into the peri-
toneal cavity. 5 Neutrophilia with a left shift occurred
in 25% of the cases. Inflammation due to trauma or
peritonitis is the most likely cause, although in a
study of experimentally induced bladder rupture, the
WBC count could not be correlated with the degree of
peritoneal inflammation. 5
Azotemia was noted in 96.2% of the cats at presen-
tation. A direct correlation between the duration of
UP and the severity of azotemia has been reported in
dogs 5 and foals. 1 Such a correlation could not be
established in this study because the exact onset of
UP remained undetermined in the majority of the
cases. Prerenal factors (e.g., dehydration) may con-
tribute substantially to this azotemia. Blood urea ni-
trogen, creatinine, and phosphorus concentrations
were higher than those reported in dogs and foals
with UP, 1,5 despite comparable durations of illness.
Cats with UP due to urethral obstruction and those
previously diagnosed with renal disease had the high-
est serum concentrations of BUN and creatinine.
Decreased renal function subsequent to urethral ob-
struction may potentiate the effects of UP. Median
duration for resolution of the azotemia after surgical
correction of the urological defect, or institution of
conservative treatment, was 36 hours. Azotemia
tended to be prolonged in cats with multiple injuries
Uroperitoneum 321
unrelated to the urinary tract. Prerenal factors were
responsible most often for this difference, although
renal factors could not be ruled out in some cases.
Pulmonary contusions prevented aggressive fluid re-
suscitation and correction of prerenal factors of
azotemia in some of the cases where UP was caused
by blunt abdominal trauma.
Electrolyte disturbances including hyperkalemia,
hyponatremia, and hypochloremia have been reported
in humans, 15 dogs, 5 and foals 1 with UP. Urine is high
in K + and low in Na + and Cl -. These electrolytes
equilibrate rapidly across the peritoneum. 5 Vomiting
leads to further decreases in total body Na + and Cl -. 5
Hyperkalemia, hyponatremia, and hypochloremia
were not consistent findings in this study as hypokale-
mia, hypernatremia, and hyperchloremia were ob-
served in some cats. Preexisting renal disease,
duration of illness, concomitant systemic disease, and
previous treatment might influence the electrolyte
changes found in UP.
Gross hematuria has been reported in humans and
dogs with urinary tract injury. 2,3,5,6,16 In humans, gross
hematuria was a consistent finding in patients with
bladder rupture. 17 In dogs with pelvic fractures, hem-
aturia was the most frequent clinical sign suggestive
of urinary tract injury. 6 It occurred most often with
bladder mucosal irregularities/clots but generally was
not associated with a ruptured bladder. 6 In the au-
thors’ study, gross/microscopic hematuria was noted
in 42.3% of cats and was observed with avulsion of
the ureter, bladder rupture, and urethral tears. How-
ever, 63.6% of cats with hematuria had concomitant
lower urinary tract disease. In these cases, hematuria
might have been attributable to lower urinary tract
inflammation rather than injury. Hematuria was noted
in 30% of cats with ruptured bladder unrelated to
lower urinary tract disease. The absence of hema-
turia, therefore, does not rule out severe urinary tract
injury.
Serosanguineous fluid was obtained via abdomi-
nocentesis in 13 of 14 cases. Fluid analysis was per-
formed in four of these cases and suggested a modified
transudate in three cases and an exudate in one case
with a ruptured bladder tumor and septic peritonitis.
The gross appearance of peritoneal effusion might be
misleading in the diagnosis of UP in cats, because it
does not resemble urine.
The results of this study confirm findings in other
species that serum and abdominal fluid creatinine
concentrations differ, and therefore they are useful in
the diagnosis of UP. 1,5,15 The large creatinine mol-
ecule does not diffuse readily across the peritoneal
membrane into the blood, leading to a gradient
between creatinine concentration in serum and ab-
dominal fluid. 15 Richardson suggested a serum creati-
nine-to-abdominal fluid creatinine ratio of 1:2 or
322 JOURNAL of the American Animal Hospital Association
greater as diagnostic for UP in foals. 1 The mean se-
rum-to-abdominal fluid creatinine ratio in this study
was 1:2 (range, 1:1.1 to 1:4.1). The corresponding K +
ratio appeared to be an equally useful indicator of
urine leakage, with a mean value of 1:1.9 (range,
1:1.2 to 1:2.4). However, the serum-to-abdominal
fluid creatinine and K + ratios (1:1.1 and 1:1.2, re-
spectively) may be very small in cats with UP. Values
for the serum-to-abdominal fluid creatinine and K +
ratios in cats with peritoneal effusion of different
etiology have not been reported in the literature. Ab-
dominal fluid K + concentrations in dogs with perito-
neal effusion from heart failure, septic peritonitis,
hemorrhage, pancreatitis, or hypoalbuminemia were
similar to those of serum. c The creatinine as well as
the K + ratio were reversed in one cat with urethral
obstruction and a ruptured bladder. In this cat, samples
for serum and abdominal fluid analysis most likely
were taken at different times. The serum creatinine
might have been measured when the cat’s urethra still
was obstructed and the bladder wasn’t ruptured, yet
the abdominal sample was obtained after relief of the
urethral obstruction and after dilution of the serum
creatinine with intravenous fluids. Accurate serum-
to-abdominal fluid urea nitrogen concentrations were
not evaluated in this study. The small urea molecules
diffuse rapidly across the peritoneal membrane into
the blood, not allowing for a gradient to be estab-
lished. 15 In dogs with UP, concentrations of urea ni-
trogen in abdominal fluid were found to be equal to
concentrations in blood. 5 Azostick readings, however,
were lower for blood than for the abdominal fluid in
this study, suggesting this parameter may be a diag-
nostic tool in cats with UP.
The results of this study are similar to previous
reports that survey radiographs may be suggestive of
urinary tract injury but are rarely diagnostic. 6 In the
majority of cases, survey radiographs showed a de-
crease in abdominal detail, supportive of peritoneal
effusion. One cat with a transected urethra had a
cranially displaced bladder.
Positive contrast radiography, including excretory
urography, cystography, and retrograde urethrog-
raphy, was diagnostic in all cases in which it was
performed, making it the method of choice for the
diagnosis of urinary tract injuries, as previously re-
ported in other species. 2,3,5,6 In humans, the accuracy
of retrograde cystography ranges from 85% to 100%2,3
and depends largely on the amount of contrast me-
dium injected. 2 False negative results may result from
inadequate distension of the bladder with contrast
medium. 2 In two studies in dogs, all urinary tract
lesions were demonstrated by contrast radiography. 5,6
Sites of urine leakage were identified in two of the three
excretory urograms performed, while the third failed to
distinguish between ureteral and bladder damage.
July/August 1998, Vol. 34
Prolonged renal excretion of dye has caused renal
damage in humans, and excretory urography should
not be performed on dehydrated animals. 18 Excretory
urography might have contributed to the deterioration
of renal function in one cat that was presented with
acute or chronic renal failure (serum creatinine, 13
mg/dl), renal calculi, and UP postnephrotomy. In an-
other cat that had an excretory urogram performed,
serum creatinine (9.5 mg/dl) remained markedly el-
evated 19 hours postsurgery. This cat had severe
azotemia (serum creatinine, 20 mg/dl) after urethral
obstruction and a urethral tear. The excretory uro-
grams on these two cats demonstrated poor renal func-
tion at the time of the radiographic studies.
Exploratory surgeries were performed in 19 cats.
Urinary tract defects were diagnosed before surgery
using contrast radiography or they were suspected
based on clinical signs and clinicopathological and
radiographic findings in 17 cats. Ruptured bladders
were incidental findings at surgery in two cats that
went to surgery for confirmed septic peritonitis and
for an abdominal wall hernia with possible bowel
rupture, respectively.
In humans, bladder rupture frequently leads to
uroretroperitoneum because the bladder is located ret-
roperitoneally. 2,3 Bladder rupture in dogs and cats
usually results in UP because of the intraperitoneal
location of the urinary bladder in these species. 10 In
this study, blunt abdominal trauma commonly resulted
in bladder rupture at the apex, while defects in the
dorsal and ventral aspects of the trigone were associ-
ated more often with urethral obstruction and trau-
matic catheterization.
Signs of peritonitis, including hyperemic perito-
neum and petechial hemorrhage in the parietal and
visceral peritoneum, were described at surgery or
necropsy in three of 24 cats. Urine is irritating to the
tissues and causes a chemical peritonitis. 10 If a uri-
nary tract infection is present before urinary tract
rupture, a septic peritonitis may develop. 10 Although
peritonitis has been reported as a consistent finding in
dogs with ruptured bladders,5 the degree of peritonitis
might differ between species, duration and amount of
urine leakage, and concurrent bacterial contamination.
Uroperitoneum might be a source of sepsis. 10 Bac-
teriological culture was positive in more than 50% of
the samples. Clinically normal dogs often have posi-
tive urine cultures. 5 Antibiotic therapy is recom-
mended in human patients with renal trauma or
urethral injuries. 19 The majority of cases in this study
received antibiotics. Broad-spectrum antibiotic therapy
should be considered in cats with UP, especially in
severely traumatized patients.
Fluid therapy and drainage of urine from the peri-
toneal cavity appear to be the most important factors
in the stabilization of patients with UP. In patients
July/August 1998, Vol. 34
with urethral disruption or obstruction, a temporary
cystostomy can be performed. 4,12 Effective urine
drainage from the peritoneal cavity can be accom-
plished with simple intra-abdominal catheter or di-
alysis catheter placement. 12 Peritoneal dialysis in
combination with fluid therapy led to a marked de-
crease in serum creatinine in all cats in which it was
instituted. Although peritoneal dialysis or temporary
cystostomy appeared to be superior in this study,
adequate urine drainage likely can be achieved by
intra-abdominal catheter placement alone.
For humans, the decision between surgical or con-
servative treatment for urinary tract leakage is based
on the site and the extent of the lesion as well as
associated injuries. 2–4,13,17,19 Although surgical repair
is the treatment of choice, urethral catheter drainage
alone is successful in patients with extra-peritoneal
bladder rupture or partial urethral tears, 3,4,13,17 and it
seems to be an appealing option in multiple injured
patients. 3 Surgical treatment of urinary tract injuries
in small animals has been described in detail. 20 Con-
servative management has been reported in animals
with bladder rupture or partial urethral tears.14,21,22 In
this study, one cat with a urethral tear was treated
successfully with urethral catheter drainage alone. In
humans and animals, urethral tears can be managed
by catheter drainage for two-to-four weeks, 4,22 after
which a urethrogram should be performed before cath-
eter removal. 4 Treatment options for disruption of the
urethra are immediate surgical repair, primary ure-
throplasty, or cystostomy drainage followed by
delayed urethroplasty. 4 In this study, temporary cys-
tostomies were performed in four cats with urethral
tears before definitive surgical repairs of the urethras.
Cystostomy catheter placement promotes patient sta-
bilization through urine drainage. 4,8 Since uremic pa-
tients are at high risk to develop complications during
anesthesia, 23 surgical correction of urinary tract leak-
age should be delayed until metabolic, fluid, and elec-
trolyte disturbances have been corrected. 5
Although only 61.5% of cats with UP were dis-
charged, the prognosis appears to be good for patients
with a treatable underlying cause and no concurrent
injuries. Those cases (n=7) that were euthanized be-
fore definitive treatment could be initiated might have
survived with aggressive therapy. Cases that died or
were euthanized after surgery generally had severe
concurrent injuries. In humans, concurrent injuries
are responsible for most of the deaths in patients with
ruptured bladders. 11 The authors noted a significant
longer median hospitalization time for cats with mul-
tiple injuries unrelated to the urinary tract compared
to those with urinary tract abnormalities only. It is
possible that patients that did not survive after sur-
gery were stabilized inadequately before surgery. A
delay in diagnosis and treatment greatly increases the
Uroperitoneum 323
mortality rate in humans and dogs with ruptured blad-
ders. 5,11 This seems logical given the severe fluid,
electrolyte, and metabolic imbalances resulting from
UP. However, no correlation was found between the
duration of illness prior to treatment and mortality.
a
Blood urea nitrogen or Azostix; Azostix; Miles Inc., Elkhart, IN
b
GraphPad InStat; GraphPad Software, San Diego, CA
c
Personal communication, Dr. D. Hughes, Department of Clinical Studies,
School of Veterinary Medicine, University of Pennsylvania, Philadelphia,
PA
Acknowledgments
The authors would like to thank Dr. Chantal Parent
for her help in preparing the manuscript.
References
1. Richardson DW, Kohn CW. Uroperitoneum in the foal. J Am Vet Med
Assoc 1983;182:267–70.
2. Carroll PR, McAninch JW. Major bladder trauma: mechanisms of injury
and a unified method of diagnosis and repair. J Urol 1984;132:254–7.
3. Cass AS, Luxemberg M. Features of 164 bladder ruptures. J Urol
1987;138:743–5.
4. Spirnak JP. Pelvic fractures and injury to the lower urinary tract.
Surg Clin Am 1988;68:1057–69.
5. Burrows CF, Bovee KC. Metabolic changes due to experimentally
induced rupture of the canine bladder. J Am Vet Res 1974;35:1083–8.
6. Selcer BA. Urinary tract trauma associated with pelvic trauma. J Am
Anim Hosp Assoc 1982;19:785–93.
7. Böhmer E. Beckenfrakturen und - luxationen bei der Katze in den Jahren
1975–1982. Inaugurations-Dissertation, Ludwig Maximilians-Universität
München, 1985.
8. Rawlings CA, Wingfield WE. Urethral reconstruction in dogs and cats.
J Am Anim Hosp Assoc 1976;12:850–60.
9. Grognet J. Transitional cell carcinoma and subsequent rupture of the
canine bladder: a case report and review of the literature. Can Vet J
1983;24:338–40.
10. Osborne CA, Low DG, Finco DR. Canine and feline urology. Philadel-
phia: WB Saunders, 1972:343–9.
11. Prather GC, Kaiser TF. The bladder in fracture of the bony pelvis:
significance of a “tear drop bladder” as shown by cystogram. J Urol
1950;63:1019.
12. Bjorling DE. Traumatic injuries of the urogenital system. Vet Clin N Am
Sm Anim Pract 1984;14:61–76.
13. Corriere JN, Sandler CM. Management of ruptured bladder: seven years
of experience with 111 cases. J Trauma 1986;26:830–3.
14. Lavoie J-P, Harnagel SH. Nonsurgical management of ruptured urinary
bladder in a critically ill foal. J Am Vet Med Assoc 1988;192:1577–9.
15. Sulivan MJ, Lackner LH, Banowsky LHW. Intraperitoneal extravasa-
tion of urine. J Am Med Assoc 1972;221:491–2.
16. Fallon B, Wendt JC, Hawtrey CE. Urological injury and assessment in
patients with fractured pelvis. J Urol 1984;131:712.
17. Palmer JK, Benson GS, Corriere JN Jr. Diagnosis and initial manage-
ment of urological injuries associated with 200 consecutive pelvic
fractures. J Urol 1983;130:712–4.
18. Feeney DA, Barber DL, Osborne CA. Advances in canine excretory
urography. Proceed, 30th Gaines Veterinary Symposium. White Plains,
New York, Gaines Dog Research Center; 1981:35–41.
19. Whitaker RH. Urological trauma. Ann Aca Med 1992;21:258–62.
20. Christie BA, Bjorling DE. Principles of urinary tract surgery. In: Slatter
D, ed. Textbook of small animal surgery. 2nd ed. Philadelphia: WB
Saunders, 1993:1415–73.
21. Osborne CA, Polzin DJ, Feeney DA, et al. The urinary system: patho-
physiology, diagnosis, treatment. In: Gourley IM, Vasseur PB, eds.
General small animal surgery. Philadelphia: JB Lippincott, 1985:
479–659.
(Continued on next page)
324 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

References (cont’d) 23. Deutsch S. Anesthetic management in acute and chronic renal failure.
Vet Clin N Am 1973;3:57–64.
22. Weaver RG, Schulz JW. Experimental and clinical studies of urethral
regeneration. Surg Gynecol Obstet 1962;115:729–36.
 Morbidity and Mortality Associated with
Anesthetic Management in Small Animal
Veterinary Practice in Ontario
During 1993, 66 small animal practices participated in a prospective study to
evaluate the incidence and details of anesthetic-related morbidity and mortality.
Considering a total of 8,087 dogs and 8,702 cats undergoing anesthesia, the
incidences of complications were 2.1% and 1.3%, respectively. Death occurred in
0.11% and 0.1% of cases, respectively. Logistic regression models were developed
and showed that a significant odds ratio (OR) of complications in dogs was
associated with xylazine (OR, 91.5); heart rate monitoring (OR, 3.2); American
Society of Anesthesiologists (ASA) 3, 4, or 5 classification (OR, 2.5); isoflurane (OR,
2.4); butorphanol (OR, 0.35); technician presence (OR, 0.26); acepromazine (OR,
0.24); ketamine (OR, 0.21); and mask induction (OR, 0.2). Complications in cats
were associated with ASA 3, 4, or 5 classification (OR, 5.3); diazepam (OR, 4.1);
intubation (OR, 1.7); butorphanol (OR, 0.45); and ketamine (OR, 0.17). Cardiac
arrest in dogs was associated with xylazine (OR, 43.6) and ASA 3, 4, or 5
classification (OR, 7.1). Cardiac arrest in cats was associated with ASA 3, 4, or 5
classification (OR, 21.6) and technician presence (OR, 0.19). This paper reports the
incidences of complications and cardiac arrest in small animal practice and identifies
common complications and factors that may influence anesthetic morbidity and
mortality. This information may be useful in comparing anesthetic management
practices. J Am Anim Hosp Assoc 1998;34:325–35.

Doris H. Dyson, DVM, DVSc, Introduction

Diplomate ACVA
M. Grant Maxie, DVM, PhD,
Diplomate ACVP
Dan Schnurr, MSc
O accurate end-tidal inhalant concentration. Veterinarians perform an-
From the Department of Clinical Studies,
Ontario Veterinary College,
University of Guelph,
Guelph, Ontario, Canada.
All correspondence should be addressed
to Dr. Doris H. Dyson,
Department of Clinical Studies,
Ontario Veterinary College,
University of Guelph,
Guelph, Ontario, Canada, N1G 2W1.
The death rate related to general anesthesia in humans has been
estimated to be as low as 1:10,000.1–3 This may be a significant
underestimation of the risk, as several studies (even from the 1990s)
indicate mortality rates as high as 0.5 to 1.5 per 1,000.4–6 Human
anesthesia is performed by specially trained practitioners using moni-
toring techniques able to detect low blood pressure, poor oxygen-
ation, arrhythmias, esophageal intubation, hypoventilation, and
esthesia with much less information, and their patients often are
monitored intermittently by technicians with limited training in anes-
thesia. The risk of mortality associated with anesthesia in animals
may be much higher than in humans.
In a prospective study of anesthetic accidents in Great Britain in
the mid 1980s, one in 679 healthy dogs and cats died.7 Veterinary
patients with recognized clinical disorders carried an enhanced risk
of death; one in 31 animals died. The only drug identified as influenc-
ing risk was xylazine. In another retrospective survey, Vermont vet-
erinarians indicated that mortality occurred in one in 1,000 dogs and
one in 1,500 cats. 8 No specific drug was identified as problematic.
This difference in mortality may be related to the differences in
anesthetic management and drug use in Great Britain and the United
States, or possibly it may be due to the retrospective, recollection

JOURNAL of the American Animal Hospital Association 325

326 JOURNAL of the American Animal Hospital Association
method used in the second study. The use of
isoflurane would not have been considered in Great
Britain at the time of the study, and isoflurane was
increasing in popularity during the time of the
study in Vermont. These authors felt that another
prospective study with a computerized data base is
needed to evaluate the risk of morbidity and mor-
tality related to anesthetic management in the
1990s.
During 1993, veterinarians in Ontario small ani-
mal practices maintained records on animals anesthe-
tized during a six-month period. These records
included details on drugs, techniques, and occurrences
perceived by the veterinarian as unexpected or com-
plicating anesthetic management. The purposes of this
study were to determine the incidence and details of
anesthetic-related morbidity and mortality and to
identify drugs or management practices which en-
hanced or reduced risk.
Materials and Methods
From January to July of 1993, 76 practices in Ontario
agreed to participate in a survey about complications
associated with anesthetic management in small ani-
mals. The majority (65) of practices were selected
from a randomly chosen group which proved to be
compliant and interested in anesthesia as determined
from a preliminary survey on anesthetic agent use.
The remainder were selected randomly from the list-
ing of small animal practices accredited by the Col-
lege of Veterinarians of Ontario. Veterinarians were
asked to record on an anesthetic log the details re-
lated to all small animals undergoing anesthesia dur-
ing the six-month period and the drugs and techniques
used on each animal. A rank of health status based on
the American Society of Anesthesiologists’ (ASA)
risk categories was requested. Healthy animals were
considered to be those within ASA 1 and 2 classifica-
tions (i.e., elective procedures in animals with no
known abnormalities or where the type of procedure
or clinical condition was considered of minor signifi-
cance). Classifications of ASA 3, 4, and 5 were used
for animals in which the clinical condition (i.e., obvious
disease or dysfunction diagnosed, ASA 3; signifi-
cantly compromised by the disease or condition, ASA
4; moribund, ASA 5) resulted in a progressive impact
on anesthetic management. In an effort to simplify
the recording process, the practices listed and num-
bered their standard protocols and assigned the spe-
cific protocol number on the anesthetic log. For
special cases failing to fit a standard protocol, practi-
tioners filled out a separate, detailed form. Whenever
a complication was noted, the same detailed form was
used to describe the anesthetic protocol and to ex-
plain the problems noted. Drug doses were not con-
sidered in this study.
July/August 1998, Vol. 34
The forms for special anesthetics and complica-
tions were standard test score forms which were
scanned and transferred to ASCII format. The forms
contained the answers to 50 multiple choice catego-
ries. The first 30 categories were answered for each
standard protocol. These categories included details
on preoperative management and evaluation, premedi-
cation, induction, maintenance, monitoring, and post-
operative drugs. Complications (both minor and
major), including cardiac arrest, were pursued in 20
categories [Appendix 1]. Veterinarians were encour-
aged to write additional details on any animal that
arrested and, when possible, postmortem examination
reports were to be included. Each practice also was
required to fill out a detailed form on a random num-
ber of cases which had a standard protocol assigned
to determine the accuracy of this method of recording.
The analysis was limited to dogs and cats due to
the small number and great variety of other species.
The anesthetic protocols and patient data were en-
tered into the computer. All scanned forms were in-
cluded in the data base. Accuracy of data entry was
assessed roughly by computing descriptive statistics
(including minimum and maximum values) on weight,
age, and regimen and by comparing a random sample
of records. All statistical analyses were carried out
using SAS.a The variables that were considered ini-
tially are listed in Appendix 2. Simple associations of
complications and cardiac arrests with drug use, tech-
niques, and ASA classification were evaluated using
chi-square (χ2 ) analysis. Separate analysis by species
was carried out due to differences noted in the χ 2 tests
between dogs and cats. Logistic regression was used
to consider the influence of age and weight on these
variables. All variables with a p less than 0.25 ini-
tially were considered in development of logistic re-
gression models to predict the risk of complications
and cardiac arrest. A combination of backward elimi-
nation and manual comparison of possible models
was used to derive the final models which included
variables with a significance of p less than 0.05. Sig-
nificant odds ratios (ORs) were calculated, indicative
of an association more (OR greater than one) or less
(OR less than one) frequently than expected (OR
equals one representing the overall incidence of com-
plications).
Results
Sixty-six veterinary practices (87% of those that were
contacted initially) participated in the study. Indi-
vidual practices reported on 25 to 841 animals. In-
cluded in the survey were 16,878 animals (including
8,087 dogs and 8,702 cats).
Duplicate, detailed forms randomly were requested
in order to assess the accuracy of the standard proto-
col assignment in the study; the forms were com-
July/August 1998, Vol. 34 Anesthesia 327

Appendix 1
Complication Guidelines
Classification of Complication
Assessment of severity Minor since easily treated
Minor since no significant consequence
Major concern created
Definition of Minor Incidents
1. Heart Rate Bradycardia (60–70 beats/min) and irregular
Bradycardia (50–70 beats/min) and regular
Normal rate but irregular
Tachycardia (clinician defined)
2. Apnea Short period causing some concern (good surgical plane)
Short period when deep plane suspected
3. Intraoperative respiratory Slow rate
concerns making stable Shallow
anesthesia difficult Panting
4. Mucous membrane color change Gray
Injected
Pale
5. Intubation difficulty Small larynx
Long soft palate
Visualization problem
Other
6. Recovery extended up to 30 minutes more than expected
7. Significant hangover
8. Excitable recovery Requiring restraint
Requiring sedation/analgesia
9. Other minor concern Explanation requested
Definition of Major Incident
1. Bradycardia <60 beats/min and irregular
<50 beats/min and regular

2. Irregular heart rate with a rapid pulse (clinician defined)

3. Cyanosis With no obvious respiratory depression
With obvious respiratory depression
4. Prolonged apnea requiring control During a surgical plane
During a deep plane
5. Collapse (loss of conciousness After premedication
or excessive sedation) After apparent recovery
6. Laryngeal problems Spasm
Edema
Bleeding/trauma
7. Impossible intubation Tracheostomy performed
Animal recovered without intubation
8. Prolonged recovery >30 min but <4 hr
>4 hr
9. Cardiac arrest Successful resuscitation
Unsuccessful resuscitation
10. Other major concern Explanation requested

pleted on 420 animals. Differences existed between premedication selected (often the use of atropine or
what the practitioner said was done on the detailed acepromazine differed) and to the technician moni-
form and the assigned protocol information in 20% of toring. The detailed forms, when available, were con-
these animals. Most of the differences related to the sidered to be the more accurate assessment except
328 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

In 78% of dogs, anesthesia was continued with an

Appendix 2 inhalant (38% with halothane, 36% with isoflurane,
Variables Determined From the Data Base and 4% with methoxyflurane) in 100% oxygen,
that Were Considered Initially in Analysis whereas 2% of the remaining dogs received oxygen
during injectable maintenance. The Bain circuit was
Drugs Management Details Other used in a third of the animals, and the circle system in
the remaining dogs was connected to a breathing sys-
Acepromazine Apnea monitor Age
tem. Technicians monitored dogs intermittently or
Atropine Bain circuit ASA* continuously throughout anesthesia in 86% of the
Butorphanol Blood pressure monitor (1, 2 cases. Mechanical apnea monitors were used com-
Diazepam Blood tests versus monly in dogs (35%), while some method of heart rate
Glycopyrrolate Heart monitor 3, 4, 5) detection (i.e., simple stethoscope, esophageal stetho-
Halothane Intubation Breed scope, electrocardiogram, or other) was used in 66% of
Innovar Laryngeal spray Weight the cases. Blood pressure measurement was unusual
Isoflurane Mask/tank induction (0.2%). Postoperative analgesia (primarily butorphanol)
Ketamine Oxygen administration was used in 16% of the dogs, and the use of nonste-
Local anesthetic Postoperative analgesia
roidal anti-inflammatories was rare (less than 1%).
Meperidine Stylet use at intubation Feline Anesthetic Management
Methohexital Technician present
Most cats (71%) were weighed, and preanesthetic evalu-
Methoxyflurane Weighed (versus estimate) ations were done without blood tests in the majority
Morphine (83%) of cats. An ASA classification was assigned in
Oxymorphone 99% of the cats, with 95% of the cats being ASA 1 or 2.
Nitrous oxide Acepromazine (65%), atropine (44%), and butor-
NSAIDs† phanol (37%) were used most commonly for pre-
Thiobarbiturate medication. Meperidine (19%) and glycopyrrolate
Xylazine (9%) were chosen less frequently. Combinations of
these drugs were common.
* American Society of Anesthesiologists’ (ASA) Anesthesia was induced with ketamine or ketamine
classification of health status combinations (including diazepam/ketamine [11%]
†
Nonsteroidal, anti-inflammatory drugs and xylazine/ketamine [7%]) in 47% of cats, inhalant
by mask in 27% of cats, and thiobarbiturate in 23% of
cats. Some incomplete records existed. Veterinarians
when related to technician monitoring. It was as- intubated 42% of anesthetized cats, with some form
sumed that technician monitoring was limited or ab- of stylet used during tube placement in 24% of these
sent if so indicated on either form. cats. Lidocaine spray or drops were applied to the
larynx in 90% of these animals.
Canine Anesthetic Management Maintenance of anesthesia was extended or supple-
Anesthetic management in dogs varied. Dogs (82%) mented by an inhalant anesthetic (28% with halothane
were weighed, and 71% were evaluated without in- and 27% with isoflurane) in 100% oxygen in 55% of
formation from blood tests. American Society of An- the anesthetized animals, whereas only 3% of cats
esthesiologists’ classifications were recorded for 99% during injectable maintenance received oxygen
of the cases (92% were ASA 1 or 2). supplementation. Almost all of the cats (98%) that
Acepromazine (68%), atropine (59%), and butor- received oxygen were connected to a Bain circuit.
phanol (37%) were the most common preanesthetic Technicians monitored cats at least intermittently dur-
medications. Meperidine (28%) and glycopyrrolate ing anesthesia in 83% of the cases. Apnea monitors
(10%) were selected occasionally. Combinations of these were used occasionally (23%), while some type of
drugs were common. Xylazine use was uncommon (1%). heart rate monitor was common (65%). Blood pres-
Anesthesia was induced with thiobarbiturates sure detection by means other than manual palpation
(52%), diazepam/ketamine (26%), and inhalant by of pulses was rare (0.1%). Postoperative analgesia
mask (11%). The remainder of recorded inductions consisted of opioids (primarily butorphanol) in 21%
consisted of fentanyl/droperidol, methohexital, and of cats and nonsteroidal anti-inflammatories in 4%.
xylazine/ketamine (less than 0.2%). Intubation was
common (77%), lidocaine laryngeal spray was used Anesthetic Complications
occasionally (12%), and use of a stylet to stiffen the The incidence of anesthetic complications was greater
tube was rare (less than 2%). in dogs than in cats (2.1% and 1.3%, respectively).
July/August 1998, Vol. 34 Anesthesia 329

Table 1 Table 2
The Incidence of Complications Related to The Frequency of Surgeries Performed
Anesthesia According to Breed* According to Species

Number Incidence Frequency

Species Breed Affected (%) Species Surgery (%)
Canine Airedale terrier 1 4 Canine Ovariohysterectomy 24*
Bulldog 3 25 Castration 20
Bull terrier 1 5 Dentistry 19
Boston terrier 1 5 Orthopedics 3
Bouvier des Flandres 1 4
Feline Ovariohysterectomy 34
Boxer 4 6
Castration 33†
Brachycephalic breeds† 12 4
Declaw‡ 27
Brittany 1 7
Dentistry 11
Fox terrier 1 8
Orthopedics 0.5
German shorthaired 1 5
pointer
* A significantly higher level of anesthetic complica-
Jack Russell terrier 5 10 tions (p of 0.016) than overall rate
Mastiff 1 7 †
A significantly lower level of anesthetic complications
Pomeranian 3 4 (p of 0.001) than overall rate
‡
Terrier (all breeds)‡ 17 4 Ovariohysterectomy or castration also was
Shih tzu 8 5 performed in almost all cases
Weimaraner 2 25
West Highland white 4 8 vided in approximately 60% of the canine cases and
terrier
in 40% of the feline cases in which complications
were noted on the anesthetic log. The problem was
Feline Himalayan 6 4
ranked as serious about 22% of the time in each
* Where the incidence within the breed was greater species. The types of problems reported were very
than 3.5% similar in both species.
†
Includes bulldog, Boston terrier, chow chow, The most commonly reported complication was
Pekingese, pug, Chinese shar pei, shih tzu related to respiration. Respiratory depression or ap-
‡
Includes all unspecified terriers, Airedale terrier, nea was noted intraoperatively in 43 dogs and 30 cats,
Australian terrier, Bedlington terrier, border terrier,
while five cats showed signs of respiratory distress
Boston terrier, bull terrier, Cairn terrier, fox terrier,
Jack Russell terrier, Kerry blue terrier, Scottish postoperatively. Difficulty with intubation was re-
terrier, Sealyham terrier, soft-coated wheaten terrier, corded in seven dogs. Eleven cats either were diffi-
West Highland white terrier, Yorkshire terrier cult to intubate or demonstrated laryngeal spasm or
edema. One endotracheal tube in a cat was plugged
with mucus. One dog and one cat aspirated their re-
The specific breeds of dogs and cats with greater than spective endotracheal tubes in recovery; the cat re-
3.5% incidence of complications are listed in Table 1. quired bronchoscopy as a result.
The most commonly performed surgeries are listed Cardiac arrhythmias also were fairly common.
in Table 2 as well as the incidence of major orthope- Tachycardia was recorded in five dogs and eight cats.
dic procedures (i.e., fracture fixation, cruciate liga- Bradycardia was found in 50 dogs compared to 12
ment repair, arthroscopy, excision arthroplasty, and cats. A greater percentage of bradycardic cats had
amputation). The surgery performed was specified in irregular rhythms accompanying the slow heart rate
94% of the cases. Chi-square analysis on the most (n=4), while only five dogs demonstrated irregular
common surgeries showed a significant difference in rhythms.
complications during canine ovariohysterectomies Undesirable recoveries were observed in many ani-
(higher, p of 0.016) and feline castrations (lower, p of mals. Recovery times were much longer than expected
0.001). in 12 dogs and 16 cats. Five dogs and seven cats
The drugs and techniques which were associated exhibited excitement at recovery which required re-
with anesthetic-related complications are listed in straint, sedation, or analgesia. One dog collapsed in
Table 3. Explanations on computer forms were pro- recovery. Other problems during recovery in cats in-
330 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

Table 3
Multiple Logistic Regression Models Related to Complications and Cardiac Arrest

Odds Standard p
Species Consequence Factors Ratio* Error Value
Canine Complication Xylazine 91.51 0.35 0.00
Heart monitor 3.21 0.29 0.00
ASA† 3, 4, or 5 2.51 0.26 0.00
Isoflurane 2.44 0.22 0.00
Butorphanol 0.35 0.26 0.00
Technician present 0.26 0.32 0.00
Acepromazine 0.24 0.21 0.00
Ketamine 0.21 0.26 0.00
Mask induction 0.20 0.48 0.00
Cardiac arrest Xylazine 43.61 0.83 0.00
ASA 3, 4, or 5 7.08 0.72 0.01

Feline Complication ASA 3, 4, or 5 5.28 0.23 0.00

Diazepam 4.08 0.44 0.00
Intubation 1.69 0.22 0.02
Butorphanol 0.45 0.22 0.00
Ketamine 0.17 0.37 0.00
Cardiac arrest ASA 3, 4, or 5 21.60 0.71 0.00
Technician present 0.19 0.27 0.02

* Association with lower incidence of consequence if less than 1 and higher incidence if greater than 1
†
American Society of Anesthesiologists’ (ASA) classification of health status

cluded prolonged hypothermia (temperature less than
37˚ C), collapse (reduced consciousness following
normal recovery), and renal failure.
Other recorded problems were rare. Subcutaneous
thiopental injections were reported in four dogs and
four cats. Urticaria was present in two dogs. Two
dogs vomited after xylazine administration, and one
seizured following administration of acepromazine,
butorphanol, and glycopyrrolate. Three dogs remained
in a light plane of anesthesia, while two dogs and one
cat required much more than the usual dose of thio-
pental for induction. Unusually deep anesthetic re-
sponses to standard drug doses were mentioned in the
comments about three cats.
Cardiac Arrest
The overall incidences of cardiac arrest were similar
in dogs and cats (1:899 or 0.11% and 1:967 or 0.10%,
respectively). Details about these animals are sum-
marized in Table 4. In healthy animals (ASA 1 and 2),
the incidences of death were 1:1,483 in dogs and
1:2,065 in cats. Only four animals were necropsied.
The postmortem examination of one dog provided no
explanation for the arrest. One cat was diagnosed
with cardiomyopathy, another with laryngospasm, and
the third cat was suspected to have died as a result of
the duration of the urethral blockage and the accom-
panying high potassium and metabolic acidosis.
Veterinarians blamed the anatomical airway confor-
mations of two dogs for the arrests, and in one of
these cases, the respiratory obstruction was not diag-
nosed until too late because of blankets placed around
the dog for rewarming. Trauma-induced respiratory
complications were considered to be the causes of
cardiac arrest in a dog following chest trauma. Of the
remaining animals, clinicians felt that deep anesthe-
sia was responsible for the arrests in two cases and an
antibiotic reaction in another. Suspected reasons for
the arrests were unavailable in 50% of the cases.
The drugs and techniques which may have influ-
enced the incidence of cardiac arrest are listed in
Table 3.
Discussion
This investigation provides practitioners with a real-
istic estimate of the risks related to anesthesia of dogs
and cats. An estimate is helpful for adequately in-
forming and preparing clients. It also provides a mea-
 Table 4
The Details on all Animals with Cardiac Arrest

Diagnosis
Age Weight (Clinician/
Species Breed (yrs) (kg) ASA* Procedure Anesthetic Routine Prearrest Complications Lived Post Mortem)
July/August 1998, Vol. 34

Canine Bulldog 1 25 — Castration Incomplete record Respiratory depression/ No Brachycephalic

cyanosis syndrome
Mixed- 4 11 4 Chest wounds Atropine/mask induction/ Excessive anesthetic No Trauma-induced
breed dog isoflurane requirements/shallow respiratory
respiration/apnea/ complications
subcutaneous emphysema
Jack Russell 3 6.5 1 Ovariohyster- Xylazine/thiopental/ Arrest in recovery No No explanation
terrier ectomy halothane
Shih tzu 5 5.5 1 Ovariohyster- Xylazine/thiopental/ Bradycardia No No explanation
ectomy halothane
Bouvier 0.1 5 1 Ear crop Acepromazine/atropine/ Collapse in recovery No Allergic reaction to
des Flandres butorphanol/thiopental antibiotic
Yorkshire terrier 0.5 1.5 1 Dentistry Acepromazine/butor- Rapid, irregular heart rate No No findings on post
phanol/atropine/ mortem
thiopental/isoflurane
Shih tzu 0.6 4 1 Castration Acepromazine/butorpha- Respiratory obstruction during No Brachycephalic
nol/ketamine recovery syndrome
Pomeranian 8 2.5 3 Dentistry Glycopyrrolate/meperi- Apnea No Deep anesthesia
dine/thiopental
Golden 12 30 4 Examination Atropine/thiopental/ Rapid, irregular heart rate/ No No explanation
retriever halothane apnea

Feline DSH† — — 2 Mass excision Incomplete record Respiratory depression/ Yes No explanation
cyanosis
DSH 8 5 3 Catheterization Mask induction/ Respiratory depression/ No High serum
for FUS‡ isoflurane apnea/cyanosis potassium/
acidosis
DSH 1 4.5 1 Castration Ketamine No warning signs No Cardiomyopathy
DSH 0.5 3 1 Ovariohyster- Acepromazine/butor- Cyanosis during recovery No Laryngospasm
ectomy/ phanol/glycopyrro-
declaw late/mask induction/
halothane
Anesthesia

(Continued on next page)

331
 332

Table 4 (cont’d)
The Details on all Animals with Cardiac Arrest

Diagnosis
Age Weight (Clinician/
Species Breed (yrs) (kg) ASA* Procedure Anesthetic Routine Prearrest Complications Lived Post Mortem)
Feline DSH — 4 1 Castration Acepromazine/butor- Apnea/cyanosis No Deep anesthesia
phanol/atropine/
thiopental
DSH 4 4.5 1 Castration/ Acepromazine/butor- No warning signs No No explanation
declaw phanol/atropine/
thiopental/halothane
DSH 13 3 4 Examination Diazepam/ketamine Rapid, irregular heart No No explanation
JOURNAL of the American Animal Hospital Association

rate/cyanosis
DSH 18 2.5 5 Dentistry Acepromazine/butor- Low heart rate/cyanosis No No explanation
phanol/atropine/mask
induction/isoflurane
DSH 9 5.5 5 Ovariohyster- Acepromazine/meperidine/ No warning signs No No explanation
ectomy/ atropine/mask induction/
pyometra isoflurane

* American Society of Anesthesiologists’ (ASA) classification of health status

†
DSH=domestic shorthair or mixed-breed cat
‡
FUS=urinary tract blockage due to feline urologic syndrome
July/August 1998, Vol. 34
July/August 1998, Vol. 34
sure by which one can evaluate the quality of anes-
thetic management within a practice. As new drugs
and techniques become popular, comparisons can be
made. Self-evaluation is important, but discipline and
quality control committees within licensing organiza-
tions may turn to these studies in veterinary practice
assessment.
It is difficult to say exactly what is being measured
by these studies. The association of a drug or tech-
nique with respiratory or cardiac arrest does not nec-
essarily implicate cause and effect. The causes of
anesthetic complications and mortality are quite com-
plex; multiple factors often are involved. The specific
anesthetic regimen or technique employed may cause
death in a small percentage (12%) of cases.9 Exami-
nation of anesthesia-related deaths in humans, which
resulted in litigation, identified principle events (e.g.,
failed intubation, drug-related problems, and equip-
ment difficulties) and several contributing factors in-
cluding inadequate supervision, poor preoperative
assessment, and failure to communicate. 10
Preexisting clinical disease or organ dysfunction
plays a significant role in morbidity and mortality.
The authors’ study supports this observation in both
dogs and cats. Others have reported similar find-
ings. 4,6,7 The original intent of the ASA classification
was prediction of risk. 11 The limitation of this system
lies with the inability to categorize patients consis-
tently. American Society of Anesthesiologists’ clas-
sification of 2 melds with ASA 3 when blood work
indicates problems not apparent clinically, and it is
obvious that all animals are not given the same work-
up. Emergency anesthesia is associated with a much
greater risk than elective anesthesia, 4 probably due to
the time limitation for stabilization of the patient.
Adequate preoperative preparation of patients may
shift the ASA classification to a less risky category.
Certain breeds have problems (i.e., higher inci-
dence of disease or anatomical abnormalities) which
may influence anesthetic management. Breed sensi-
tivity to anesthetics is mentioned commonly by cli-
ents and breed associations. Pekingese dogs have been
noted to have a high incidence of mortality.7 In the
authors’ study, three of the nine dogs experiencing
cardiac arrest were brachycephalic, and two of these
developed cardiac arrest secondary to obvious respi-
ratory obstruction. Respiratory complications were
high in anesthetized bulldogs. It is well known that
brachycephalic breeds present a greater challenge for
anesthesia.12 It is surprising that Jack Russell terriers
had such a high incidence of complications; evalua-
tion of individual cases provided no clues for the
increased risk. Only the Himalayan stood out within
the feline group for complications, and the incidence
was not very high. It is possible that the brachycephalic
anatomy of some Himalayans enhanced their compli-
Anesthesia 333
cation incidence. Persians have significant brachyce-
phalic anatomy; however, an increased incidence of
respiratory complications was not determined.
Possibly the risk that this study evaluates is related
to human observational and judgment skills. The fre-
quent error determined in human anesthetic manage-
ment was inadequate monitoring of the patient.10,13
Monitoring by technicians (at least intermittently) was
associated with a significant difference in reported
canine complications and feline cardiac arrests. Rec-
ognizing complications other than cardiac arrest re-
quires monitoring; therefore, one might think that
more complications would be detected with vigilant
monitoring. However, complications were reduced.
Technicians monitor depth of anesthesia and may re-
spond to minor changes (i.e., shallow respiration,
heart rate trends) before a complication arises. This
fact emphasizes the need to promote technician train-
ing (especially in monitoring the depth of anesthesia)
and to respect the importance of monitoring in a prac-
tice. Two anesthetic deaths were attributed to deep
anesthesia which was not corrected or detected in
time. Use of monitors for detection of respiratory or
heart rate appeared to have little impact on reducing
morbidity or mortality. Interpretation and assessment
of information from monitors and other related signs
of anesthetic depth are required to make accurate
judgments. The incidence of complications actually
increased with the use of heart rate monitors, and this
may be related to improved detection. Quite likely
the monitors were not instrumental in promoting fine
adjustments in the anesthetic management due to the
limited correlation between anesthetic depth and heart
rate. 14 It may be that actions were not taken until
significant changes were noted that would be re-
portable in this study. Four animals arrested dur-
ing recovery in this study, and many recovery
complications could have been prevented with en-
hanced vigilance; in the study from Britain,
approximately 25% of the fatalities occurred post-
operatively. 7 Monitors are unlikely to replace the
technician for assessment of patients postopera-
tively, but they provide additional information
which enhances the technician’s ability to make
valid judgments intraoperatively.
A significant aspect of this research is the defini-
tion of drugs and techniques which could be replaced
or promoted to improve anesthetic outcome. The au-
thors’ findings agree with those of Clarke and Hall7
about the increased risk associated with xylazine in
dogs. Xylazine was part of the protocol in 25% of the
dogs with reported complications. The complication
reported most commonly with xylazine was bradycar-
dia, as expected with this alpha-2 agonist. Two of the
animals given xylazine, thiopental, and halothane
went on to arrest. The selection of dosages, monitor-
334 JOURNAL of the American Animal Hospital Association
ing techniques, and other circumstances could influ-
ence outcome, so it is difficult to conclude a specific
cause; but caution in using xylazine during general
anesthesia is recommended. If reasonable alternatives
exist, it would be feasible to use them. The authors
did not consider the use of xylazine for chemical
restraint alone in this study. Xylazine was used only
in association with ketamine in cats in this study and
was found to be comparable in safety to other regi-
mens. No evaluation of the interaction of xylazine
with other general anesthetic agents in cats was possible.
No other drugs or techniques stood out as remark-
ably as xylazine. Isoflurane was not used in the study
done in Britain, 7 and its use was more popular in this
study than at the time of the Vermont study (36%
versus 13% in dogs and 27% versus 10% in cats,
respectively). 8 Isoflurane was identified as a variable
which was associated (2.6 times more often than ex-
pected) with anesthetic complications in dogs. The
most common complication reported with isoflurane
was respiratory depression, assumed by the practi-
tioner to be related to a brief period of deep anesthe-
sia. Isoflurane also may cause respiratory depression
in patients at an appropriate anesthetic depth. Due to
the rapid changes in anesthetic depth with this rela-
tively insoluble agent, it is easy to deepen patients
quickly, and respiratory depression is expected with
deeper planes of anesthesia. 15
The OR reported with diazepam must be consid-
ered in context. Diazepam always was used in associa-
tion with ketamine in cats. Examination of the incidence
of complications with this combination of drugs was
not significantly different than the overall rate.
Intubation was associated with an increased risk of
complications in cats. Ten percent of complications
were related to intubation in cats. The suggestion of
an increase in risk with intubation is so minor that
intubation should not be avoided in cats if the dura-
tion or type of procedure warrants it. Being prepared
to intubate and monitoring for adequate respiration
may be sufficient for short procedures in cats.
Duration of anesthesia was not considered in this
study, but one might question its impact. The major-
ity of cats being castrated were not intubated, while a
greater percentage of cats undergoing ovariohyster-
ectomy were intubated. Duration of anesthesia corre-
lates with mortality in humans.4 A tenfold increase in
mortality was reported as anesthesia duration in-
creased from less than 30 minutes to between 30 and
179 minutes. The results related to castration in cats
and intubation may be secondary to the duration of
anesthesia. Longer duration of anesthesia may con-
found the interpretation of negative impact of other
drugs as well.
This study identified a number of drugs that ap-
peared to be associated with a reduced incidence of
July/August 1998, Vol. 34
complications. Clarke suspected that acepromazine
was advantageous in anesthetic management. 7 The
authors did not show that acepromazine influenced
mortality, but acepromazine may reduce the chance
of complications related to anesthesia in dogs. The
antiarrhythmic effect, the reduction in minimum al-
veolar concentration (MAC) of inhalant anesthetic, or
the influence on smoothing recovery could be the expla-
nation. Since blood pressure was not measured in this
study, no comments regarding hypotension can be made.
Ketamine was much more common in this study
than in Clarke and Hall’s study. 7 Ketamine was asso-
ciated with a lower-than-expected complication rate
in both dogs and cats in this study. The sympathetic
stimulation associated with ketamine may reduce the
incidence of bradyarrhythmias and significant hy-
potension. Clarke and Hall showed an increase in
mortality in cats given ketamine with xylazine, but
not in cats given ketamine alone.7 Myocardial dam-
age has been detected in cats that died following
anesthesia with xylazine/ketamine, which may have
been related to myocardial hypoxia. 16 The use of
ketamine with xylazine was lower in this study than
in the Vermont study (7% versus 25% in cats), where
the combination did not appear to contribute to mor-
tality. An earlier, well-publicized report in Ontario 17
and the teaching strategy at the Ontario Veterinary
College likely are responsible for this difference.
Early work with the combination reported safety
which was comparable to that determined in this study
with xylazine/ketamine; approximately 1:2,300 healthy
cats died. 18 This similarity and the difference noted
from the study of Clarke and Hall may be related to
the selection and limitation of use to healthy animals
in this study.
Inclusion of butorphanol in the anesthetic regimen
was associated with a smaller OR for complications.
This may be related to its analgesic and sedative
effects which can reduce the need for deeper anesthe-
sia and can smooth recovery. Although postoperative
analgesia was not noted to be influential, the presence
of butorphanol as part of premedication may extend
sufficiently into recovery, considering the short dura-
tion of most practice surgeries.
Mask induction of dogs was associated with re-
duced complications in this study. The advantage of
this technique may relate to use in critical patients,
where cautious titration of anesthetic administration
is required.
This study on anesthetic morbidity and mortality
in small animals indicates that the incidence of car-
diac arrest in dogs and cats is less than reported in
Britain 7 and not remarkably different than that re-
ported in Vermont 8 or in recent studies in humans. 4–6
One might speculate on the improvement observed
with time. Within the last 15 years the authors have
July/August 1998, Vol. 34
seen increased undergraduate veterinary education in 3.
anesthesia, more specific technician training in the 4.
area of anesthetic monitoring (as well as greater tech-
nician employment), and continuing education in in-
5.
tensive care and anesthesia; all could be making an
impact. Veterinarians apply this knowledge intelli-
gently to select the more appropriate agents (or to
6.
eliminate those with a greater potential for adverse
effects in the specific individual case). Continued
advances in training could improve the statistics further. 7.
Veterinarians must be cautious about the interpre-
tation of drug safety from these types of studies. The 8.
difference shown between dogs and cats with xylazine
9.
may be related to the fact that xylazine in dogs was
associated with several other anesthetic agents while 10.
xylazine only was used in cats in association with
ketamine in this study. Use of acepromazine in 11.
healthy, young patients may reduce the induction and 12.
maintenance dose of anesthesia and smooth recovery,
but it could result in severe hypotension in very old,
13.
debilitated, or dehydrated animals, especially if anes-
thetic dose adjustment is not made properly. 19 14.
Isoflurane use could be limited to critical patients for
the advantages of better cardiac output, reduced
15.
arrhythmias, and rapid dose adjustments; 15 but it also
can be used satisfactorily in any patient with proper 16.
monitoring and management. This study cannot pro-
17.
duce absolute conclusions on drug selection. Proper
preoperative stabilization, intelligent use of drugs 18.
(dose and technique possibly being more important
than choice), careful observation of the patient until 19.
recovery is complete, and appropriate responses to
early signs of deep anesthesia, bradycardia, hypo-
ventilation, or hypotension are likely to make a more
significant difference in morbidity and mortality than
either the elimination of specific drugs or the addition
of any new agent. Whenever an anesthetic-related death
occurs, it is essential to evaluate the details to deter-
mine if there is some factor that requires improve-
ment which may help to avoid another incident.
a
Statistical Analysis Software package; SAS Institute, Inc., Cary, NC
Acknowledgments
This research was supported by a grant from Pet Trust.
The authors thank the veterinarians and techni-
cians who not only were willing to contribute a lot of
time and effort to this study but were patient with the
time it has taken for these results to be made available.
References
1. Maaloe R, Hansen CL, Pedersen T. Death under anesthesia. Definition,
causes, risk factors and prevention. Ugeskr Laeger 1995;157:6561–5.
2. Kubota Y, Toyoda Y, Kubota H, et al. Frequency of anesthetic cardiac
arrest and death in the operating room at a single general hospital over
a 30-year period. J Clin Anesthesiol 1994;6:227–8.
Anesthesia 335
Lunn JN, Mushin WW. Mortality associated with anaesthesia.
Anaesthesia 1982;37:856.
Pedersen T, Eliasen K, Hendrksen E. A prospective study of mortality
associated with anaesthesia and surgery: risk indicators of mortality in
hospital. Acta Anaesthesiol Scand 1990;34:176–82.
Schwilk B, Friess L, Friesdorf W, Ahnefeld FW, Georgieff M. Preopera-
tive risk factors and intraoperative and postoperative risk management
in 11,890 anesthesias. Initial results of a prospective study. Anaesthesiol
Intensivmed Notfallmed Schmerzther 1993;28:484–92.
Forrest JB, Rehder K, Cahalan MK, Goldsmith CH. Multicenter study of
general anesthesia. III. Predictors of severe perioperative adverse out-
comes. Anesthesiol 1992;76:3–15.
Clarke KW, Hall LW. A survey of anaesthesia in small animal practice:
Assoc Vet Anaesthesiol/Brit Sm Anim Vet Assoc report. J Assoc Vet
Anaesthesiol 1990;17:4–10.
Dodman NH, Lamb LA. Survey of small animal anesthetic practice in
Vermont. J Am Anim Hosp Assoc 1992;28:439–45.
Duncan PG. Editorial: who’s to blame? Can J Anaesthesiol 1992;
39:110–3.
Gannon K. Mortality associated with aneaesthesia. A case review study.
Anaesthesia 1991;46:962–6.
Ross AF, Tinker JH. Anesthesia risk. In: Miller RD, ed. Anesthesia. 3rd
ed. New York: Churchill Livingston, 1990:715–42.
Short CE. Congenital problems in canine breeds. In: Short CE, ed.
Principles and practice of veterinary anesthesia. Baltimore: Williams &
Wilkins, 1987:303–7.
Memery HN. Anesthesia mortality in private practice. A ten-year study.
J Am Med Assoc 1965;194:1185–9.
Dyson DH. Assessment of three audible monitors during hypotension in
anesthetized dogs. Washington: Proceed, Ann Mtg Am Coll Vet
Anesthesiol, 1993:25.
Dohoo SE. Isoflurane as an inhalational anesthetic agent in clinical
practice. Can Vet J 1990;31:847–50.
Van der Linde-Sipman JS, Hellebrekers LJ, Lagerwey E. Myocardial
damage in cats that died after anaesthesia. Vet Quart 1992;15:91–4.
Gillick A. High-frequency complaints. Ontario Vet Assoc Newsletter
1981;5:12.
Arnbjerg J. Clinical use of ketamine-xylazine in the cat. Nord Vet Med
1979;31:145–54.
Boyd CJ, McDonell WN, Valliant A. Comparative hemodynamic effects
of halothane and halothane-acepromazine at equipotent doses in dogs.
Can J Vet Res 1991;55:107–12.
 Early Detection of Canine Hip Dysplasia:
Comparison of Two Palpation and
Five Radiographic Methods
Hip joint laxity was evaluated in four breeds (i.e., greyhound, Labrador retriever, Irish
setter, hound mixed-breed) of puppies (n=32) by Ortolani’s and Bardens’ maneuvers,
by subjective assessment of radiographs (Orthopedic Foundation for Animals [OFA]
method), and by four radiographic measurement indices. Puppies were studied at
four, six-to-10, 16-to-18, and 52 weeks of age. The purpose of this study was to
compare palpation and radiographic methods of hip laxity detection in puppies for
predicting the development of degenerative joint disease (DJD) by one year of age.
Twenty-seven (42%) hips developed DJD. Ortolani’s method was not a reliable
predictor of hip dysplasia at six-to-10 weeks; it was significantly predictive at 16-to-
18 weeks but had a high incidence of false negatives. Bardens’ and subjective (OFA)
assessment methods were not reliable at six-to-10 or 16-to-18 weeks. Radiographic
measurements taken with femurs in a neutral position and hips distracted (distraction
index [DI] and Norberg angle) and measurements taken with femurs extended in
OFA position (Norberg angle) of six- to 10-week-old puppies accurately predicted
DJD occurrence by one year of age (p less than 0.01). Distraction index
measurement (PennHIP method) was the most accurate in predicting the
development of DJD (p less than 0.001). Distraction index radiography in puppies
six-to-10 and 16-to-18 weeks of age was the most reliable predictor of hip dysplasia.
Norberg angle measurement was more reliable during hip distraction than when hips
were measured in the OFA position in 16- to 18-week-old puppies, but had similar
reliability in six- to 10-week-old puppies. J Am Anim Hosp Assoc 1998;34:339–47.

William M. Adams, DVM Introduction

R. Tass Dueland, DVM, MS
Jeff Meinen, DVM
Robert T. O’Brien, DVM, MS
Elizabeth Giuliano, DVM
Erik V. Nordheim, PhD
O recently reported significant reduction in the incidence of CHD in
Canine hip dysplasia (CHD), first reported by Schnelle over 60 years
ago, 1 may be defined as hip laxity of genetic origin. Hip laxity
frequently results in radiographic signs of degenerative joint disease
(DJD) and clinical lameness. Canine hip dysplasia continues to plague
many breeds despite 25 years of selective breeding based on evalua-
tion of hip conformation using a standardized radiographic view
recommended by the Orthopedic Foundation for Animals (OFA). 2,3
Reported incidence of CHD in the four most-frequently OFA-evalu-
ated breeds (Labrador retriever, golden retriever, rottweiler, and Ger-
man shepherd dog) ranges from 14% to 23% (mean, 21%).3 The OFA
only one (i.e., rottweiler) of these four breeds between 1972 and 1990.3
Success in reducing CHD incidence is limited by the insensitivity
and timing of detection methods which result in failure to remove

From the Department of Surgical Sciences (Adams, Dueland, Meinen, O’Brien,

Giuliano), School of Veterinary Medicine, University of Wisconsin, 2015 Linden
Drive West, Madison, Wisconsin 53706 and the Department of Statistics
(Nordheim), College of Letters and Science and Department of Forestry,
College of Agricultural and Life Sciences, University of Wisconsin, 1630 Linden
Drive, Madison, Wisconsin 53706.

JOURNAL of the American Animal Hospital Association 339

340 JOURNAL of the American Animal Hospital Association
Table 1
Table 1—Comparison of distraction index (DI) variation over
time for four breeds (greyhound, Labrador retrievers, Irish
setters, hound mixed-breed dogs) of puppies. Indices were
measured from hip radiographs taken under anesthesia with the
hind limbs in a neutral position (PennHIP method). Means and
standard deviations at four-to-seven ages are shown. Note the
relative consistency between six-to-10 weeks of age and 52
weeks of age. Greyhounds and Labrador retrievers were mea-
sured at four weeks of age; note the much greater laxity
compared to later measurements of the same hips. Greyhounds
had significantly tighter hips than the other three breeds.
affected animals from the breeding pool. Alternative
methods espousing earlier and more sensitive detec-
tion of CHD have been investigated.4–7 Radiographic
detection of hip joint instability and histological evi-
dence of acetabular remodeling have been documented
in puppies as young as seven weeks.8 Progression of
radiographic subluxation and histological remodeling
of dysplastic hips by 12 weeks of age was described
as dramatic.8 The potential of a screening method for
very early detection of CHD motivated the investiga-
tion reported here.
The purposes of this study were to compare the
predictability of seven methods of hip laxity detec-
tion with occurrence of DJD by one year of age and to
determine how early each method could be applied to
puppies accurately as a screening process for CHD.
Five of the methods have been reported by others as
effective ways of detecting CHD in puppies as early
as four months of age. 3,4,6,7 In addition, two radio-
graphic methods which utilized Norberg angle mea-
surements (in a distraction view and in a compression
view) were evaluated.
Materials and Methods
Two litters of greyhounds (GHs; n=12) and a litter of
Labrador retrievers (LRs; n=4) first were examined at
four weeks; two litters of Irish setters (ISs; n=12)
first were examined at six-to-seven weeks; and a lit-
ter of hound mixed-breed puppies (HMs; n=4) first
were examined at 10 weeks of age. These examina-
July/August 1998, Vol. 34
tions were followed by sequential hip examinations
through 52 weeks of age (n=32). Greyhounds were
chosen because of the very low breed incidence of hip
dysplasia; the LRs intentionally were bred from par-
ents known to have hip dysplasia; the ISs were bred
from OFA-certified “good” parents; and the HM pup-
pies were from unknown parentage.
Puppies from four-to-16 weeks of age were anes-
thetized by mask induction using isoflurane for all
palpation and radiographic studies. Older puppies re-
ceived subcutaneous preanesthetic (i.e., butorphanol
[0.2 mg/kg body weight] plus acepromazine [0.1 mg/kg
body weight]) prior to mask induction. All puppies
were placed in homes for the duration of the study
and kept as pets.
Three subjective hip evaluation methods (i.e.,
Ortolani’s maneuver,9 Bardens’ maneuver,6 and ex-
tended-hip radiography [OFA method 2]) were tested.
In addition, four radiographic measurement methods
(i.e., distraction index [PennHIP method4 ], Norberg
angle with hind legs extended, 5,11 Norberg angle with
hind legs neutral and distracted, and Norberg angle
with hind legs neutral and compressed) of hip evalua-
tion were tested.
A positive Ortolani’s maneuver consisted of a pal-
pable “clunk” when a subluxated hip was reduced
while the puppy was positioned in lateral recumbency.
A positive Bardens’ maneuver consisted of a 2 mm or
greater estimation of palpable hip laxity. All palpa-
tion maneuvers were performed by one of the authors
(Dueland). Extended-hip radiographs were analyzed
subjectively by one of the authors (Adams) and a
reader for the OFA, a in a blinded fashion, using crite-
ria established by the OFA.10 Distraction indices (DIs)
were measured as previously reported. 4
These examinations were performed as soon as
puppies were obtained, and they were repeated at six-
to-eight, 10-to-12, 16-to-18, 24-to-26, and 52 weeks
of age for a total of three-to-seven examinations per
hip. Four GH puppies (eight hips) were examined
only three times (at four, 26, and 52 weeks of age) as
controls to assess any deleterious effects the seven
hip manipulation episodes might have on their litter
mates. All other puppies were examined at six-to-10
weeks of age, all were evaluated at 52 weeks of age,
and all but the four control GHs were examined at 16-
to-18 weeks of age—for a total of 348 individual hip
evaluations using the seven previously described
methods. Greyhound and LR puppy hips also were
examined at four weeks of age to compare consis-
tency of measurements as the puppies matured [Table
1].
On the extended-hip view taken at 52 weeks, three
board-certified radiologists (Adams, LJ Forrest, and
O’Brien) and a board-certified surgeon specializing
in orthopedics (Dueland) independently evaluated, in
July/August 1998, Vol. 34
Figure 1—Irish setter #A7 at 52 weeks of age has degenerative
joint disease (DJD) of both hips. Morgan lines (enthesophytes)
are present bilaterally (open arrows), and other stress lines also
are present bilaterally (solid black arrows). In addition, sublux-
ation of the left femoral head and mild remodeling of the cranial
margin of the left acetabulum are present. Ortolani’s and Bardens’
signs were negative in both hips at seven and 17 weeks of age,
but the Ortolani’s sign was positive in both hips at 52 weeks. A
positive Bardens’ sign was recorded in the right hip at 52 weeks.
Distraction indices are 0.53 (right hip) and 0.69 (left hip).
Norberg angles are 107˚ (right hip) and 90 ˚ (left hip).
Figure 2—Labrador retriever #5, 52 weeks old, has no degen-
erative joint changes. The right femoral head does not appear
well aligned to the acetabulum, but there is slight rotation of that
femur, potentially contributing to the less than ideal appear-
ance. Ortolani’s sign was negative for both hips at eight weeks,
but was positive at 12, 16, and 52 weeks of age. Bardens’ sign
was negative at eight, 12, and 16 weeks, but was positive at 52
weeks. Distraction indices were 0.41 (right hip) and 0.43 (left
hip). Norberg angles were 103˚ (right hip) and 103 ˚ (left hip).
a blinded fashion, all hips for evidence of DJD. De-
generative joint disease was defined as two or more
stress lines at the joint capsule attachments or one or
more stress lines and femoral head malalignment (i.e.,
subluxation) [Figure 1]. Absence of a stress line lat-
Canine Hip Dysplasia 341
Figure 3—Irish setter #A2, 52 weeks old, has a Morgan line
(enthesophyte) on the right femoral neck (open arrow), but has
no other stress lines and no coxofemoral subluxation. These
hips were recorded as negative for degenerative joint changes.
Slight rotation of the pelvis is causing asymmetry in the appear-
ance of the two hips. Ortolani’s sign was negative for both hips
at seven and 52 weeks of age. Bardens’ sign was positive for the
left hip at seven weeks but was negative for both hips at 52
weeks. Distraction indices were 0.31 (right hip) and 0.28 (left
hip). Norberg angles were 110˚ (right hip) and 105 ˚ (left hip).
eral to the femoral head (i.e., Morgan line) 12 and no
other stress lines/proliferations on the femoral neck
or acetabulum but with femoral head subluxation or
suboptimal alignment was not regarded positive for
DJD [Figure 2]. Conversely, if only a Morgan line
was evident, and no subluxation was observed on the
extended-hip view, this was not regarded as being
positive for DJD [Figure 3]. Consensus of three out of
four readers that DJD had developed was recorded as
being positive.
For statistical analysis, hips examined at six-to-10
weeks of age were grouped, those examined at 16-to-
18 weeks of age were grouped, and those examined at
50-to-52 weeks of age were grouped. The graph in
Table 1 is reported at actual age at time of measurement
for each group of puppies. Methods used to analyze data
included logistic regression and analysis of variance
(ANOVA). Significance was set as p less than 0.01.
The primary statistical tool used to determine
which of the six methods best predicted DJD was
logit analysis or logistic regression. 13 For each of 18
combinations of age groups and methods statistically
analyzed [Table 2], a logistic regression was per-
formed with occurrence or nonoccurrence of DJD as
the response variable. The p value for each analysis
was compared with a threshold value of 0.01 in order
to minimize the probability of predicting a hip devel-
oping DJD when in fact it did not. The results [Table
2] provide the actual p value so that the reader may
compare with some alternative threshold. In addition
to p value, the authors calculated the percentage of
correct prediction, number of false negatives, and num-
ber of false positives for each of the 18 combinations.
For the radiographic predictors (all measured on a
continuous scale), a hip was predicted to have DJD if
342 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

Table 2
Accuracy of Degenerative Joint Disease (DJD) Prediction Methods at Three Ages

Method Data Six-to-10 Wks of Age 16-to-18 Wks of Age 50-to-52 Wks of Age
Ortolani’s p value 0.9714* 0.0023 0.0001
maneuver n 51 47 59
% correct 54.9 72.3 88.1
No. of false negatives 23 10 2
No. of false positives 0 3 5

Bardens’ p value 0.9679* 0.9627* 0.0194

maneuver n 51 47 59
% correct 56.9 57.4 66.1
No. of false negatives 22 20 19
No. of false positives 0 0 1

Norberg p value 0.0022 0.0012 0.0027

angle n 51 50 59
OFA† view % correct 66.7 70 79.7
No. of false negatives 8 5 10
No. of false positives 9 10 2

Norberg p value 0.0122 0.2343 0.0252

angle n 51 50 59
compression % correct 64.7 50 64.4
view No. of false negatives 7 10 15
No. of false positives 11 15 6

Norberg p value 0.0007 0.0015 0.0002

angle n 51 50 59
distraction % correct 68.6 80 86.4
view No. of false negatives 8 3 3
No. of false positives 8 7 5

Distraction p value 0.0001 0.0002 0.0001

index n 51 50 59
% correct 78.4 82 88.1
No. of false negatives 5 2 2
No. of false positives 6 7 5

* Due to data structure, calculated p value is larger than it should be

†
OFA=Orthopedic Foundation for Animals

the resulting fitted logistic equation led to a probabil-
ity greater than 0.5 that the hip would develop DJD.
The one-way ANOVA was used to compare radio-
graphic results at different time points. Finally, one-
way ANOVA was used to compare two groups of
GHs (one group [i.e., the control] examined only three
times and the other group examined seven times).
Results
Both palpation methods resulted in very high num-
bers of false-negative determinations in six- to 10-
week-old puppies [Table 2]. This false-negative
incidence remained high in 16- to 18-week-old pup-
pies. Similarly, radiographic subjective assessment
of hip conformation (using the OFA method) in six-
to 10-week-old puppies resulted in a very high inci-
dence of false-negative readings. This false-negative
incidence was still quite high in 16- to 18-week-old
puppies. Of the four radiographic measurement meth-
ods used at six-to-10 weeks and 16-to-18 weeks, the
DI and Norberg angle measured in neutral-positioned
hips during distraction were the most promising pre-
dictors of DJD at one year of age. A significant rela-
tionship for both time points also was noted between
the Norberg angle measured in the extended-hip
(OFA) view to subsequent development of DJD.
Palpation Methods
Ortolani’s and Bardens’ maneuvers were performed
at 340 hip evaluation times (98% of evaluations). All
27 hips diagnosed as having DJD at 52 weeks did
have Ortolani’s assessment at six-to-10, 16-to-18, and
52 weeks; false-negative Ortolani’s signs (negative
Ortolani’s sign, but did develop DJD) recorded at
July/August 1998, Vol. 34
Table 3
Table 3—Distraction index (DI) comparison between grey-
hound hips and hips of three other breeds (Labrador retriever,
Irish setter, and hound mixed-breed puppies) combined. Means
and standard deviations at five ages (four ages for Irish setters)
are shown. Although there was a significant difference in DI of
the greyhounds between eight and 16 weeks, the difference in
DI for the other breeds combined and for DJD-positive puppies
only (not shown) was not significant between eight and 16
weeks nor between eight and 52 weeks.
these three ages were 85%, 37%, and 7%, respec-
tively. Conversely, false-positive Ortolani’s signs
were recorded in 0% (zero of 24 hips), 15% (three of
20 hips), and 16% (five of 32 hips) at these three
ages, respectively. Only four (15%) of 27 hips which
developed DJD had positive Ortolani’s signs on as-
sessment at six-to-10 weeks of age, although no false
positives were recorded at this age. As with the
Ortolani’s maneuver, results of the Bardens’ maneu-
ver were recorded only as positive or negative. Find-
ings were very similar to Ortolani’s maneuver results
at six-to-10 weeks. False-negative Bardens’ signs re-
corded at six-to-10, 16-to-18, and 52 weeks were
81%, 74%, and 70%, respectively. Only 19% of hips
which developed DJD were Bardens’ sign positive on
assessment at six-to-10 weeks of age, and again, no
false positives were recorded.
Subjective Radiographic Assessment (Orthopedic
Foundation for Animals [OFA] Method)
Degenerative joint disease was diagnosed in 27 (42%)
of 64 hips at 52 weeks of age. No DJD (0%) was
found in the 24 GH hips. Degenerative joint disease
was diagnosed in three (38%) of eight LR hips, 16
(67%) of 24 IS hips, and eight (100%) of eight HM
hips. Five (8%) of 64 hips had abnormal conforma-
tion (i.e., malalignment of femoral head with acetabu-
lar margin), 50% or less of the femoral head beneath
the acetabulum, or both; but they had no clear evi-
dence of DJD at 52 weeks. These five were deleted
from statistical analysis and are not included in Table
2. On subjective (OFA method) evaluation for hip
dysplasia using the extended-hip view, the two read-
Canine Hip Dysplasia 343
ers disagreed in 57 (21%) of 270 hip evaluations of
immature puppies six-to-18 weeks of age. Range of
disagreement by breed was 5.6% (GH) to 38% (LR).
Comparing these results with consensus diagnosis of
DJD at 52 weeks of age, both readers had a high
incidence of false-negative assessments. Of hips
which had DJD at 52 weeks, 24 (89%) of 27 were
assessed negative for hip dysplasia at six-to-10 weeks
of age and 15 (56%) of these same 27 hips still were
assessed negative for hip dysplasia at 16-to-18
weeks of age. Of hip evaluations on six- to 10-
week-old puppies which had no DJD at 52 weeks,
three (6%) of 52 were assessed positive for hip
dysplasia (false positives). No false positives were
recorded on 16- to 18-week-old puppies.
Distraction Index
The DI range for all hips, including all ages, was 0.05
to 1.0 and varied by breed [Table 1]. From eight
weeks on, all greyhounds had DIs less than 0.28,
despite ranging from 0.36 to 0.77 at four weeks of
age. Measurements were difficult at four weeks of
age due to the large amount of unossified bone; sub-
chondral ossification by six-to-eight weeks of age
was adequate for measurement. Mean DIs at six-to-
eight and 52 weeks were 0.18 and 0.10, 0.64 and 0.53,
and 0.48 and 0.46 for GHs, LRs, and ISs, respec-
tively. Mean DIs at 10 and 52 weeks for HMs were
0.65 and 0.62. When data was combined for the three
breeds at risk for hip dysplasia and was compared to
the data for GHs, despite large standard deviations in
the combined breeds group, there was no overlap in
DI range at any age between these two groupings
[Table 3].
At six-to-10 week and 16-to-18 week measure-
ments, hips with DIs of 0.31 to 0.41 comprised 19%
(five of 27 hips) and 7% (two of 27 hips), respec-
tively, of hips which later developed DJD. The lowest
DI in a hip which developed DJD by one year was
0.26 (measured at 52 weeks of age). Distraction index
in this hip was 0.35 at eight weeks. A DI less than
0.26 was measured in 24% (12 of 51 hips), 30% (15
of 50 hips), and 44% (26 of 59 hips) of all hips
analyzed from six-to-10 weeks, 16-to-18 weeks, and
one year of age, respectively.
At six-to-10 week and 16-to-18 week measure-
ments, most hips (90% [nine of 10 hips] and 87% [13
of 15 hips], respectively) with DIs greater than 0.60
developed DJD by one year. The five hips with DIs
greater than 0.70 at six-to-eight weeks developed DJD
by one year. Five (83%) of six hips with DIs greater
than 0.70 at 16-to-18 weeks developed DJD by one
year. Of all hips that developed DJD, their respective
DI means and medians by age grouping were 0.56 and
0.60 (range, 0.31 to 0.77) at six-to-10 weeks; 0.61
and 0.57 (range, 0.33 to 0.92) at 16-to-18 weeks; and
344 JOURNAL of the American Animal Hospital Association
0.56 and 0.61 (range, 0.26 to 0.71) at 52 weeks. The
most remarkable change in DI was in one dog which
had two hips that were luxated (DI, 1.0) at 26 weeks;
but by 52 weeks, the DIs had decreased to 0.63 and
0.67, respectively.
Norberg Angles
Extended-Hip (OFA) View
The Norberg/extended-hip (NorOFA) angles for all
breeds at six-to-52 weeks of age ranged from 74˚ to
116˚. No hip developed DJD that had a NorOFA angle
greater than 107˚. However, none of the 51 hips mea-
sured at six-to-10 weeks and only three (6%) of the
50 hips measured at 16-to-18 weeks of age had
NorOFA angles greater than 107˚.
For hips with angles less than 95˚ at six-to-10
weeks of age, 19 (68%) of 28 developed DJD. Hips
with angles less than 95˚ at 16-to-18 weeks (n=8) and
one year of age (n=11) all developed DJD. However,
seven (26%) of the 27 DJD hips had angles of 105˚ to
107˚ at one year of age.
Neutral-Positioned Hips Measured During
Distraction (NorDis)
Norberg/distraction angles (NorDis) were decreased
predictably for all breeds except the GHs (range, 58˚
to 104˚ for the other three breeds and 75˚ to 109˚ for
GHs at six-to-52 weeks). No hip developed DJD that
had a NorDis angle greater than 91˚. Fourteen percent
of 51 hips measured at six-to-10 weeks and 41% of
hips measured at 16-to-18 weeks of age had NorDis
angles greater than 91˚. Of angles less than 85˚ at six-
to-10, 16-to-18, and 52 weeks of age, 69%, 92%, and
100%, respectively, developed DJD by one year of
age. However, specificity of the 85˚ cut-off varied
between age brackets; at six-to-10 weeks, none of the
12 hips that measured at greater than 84˚ developed
DJD, whereas 15 (41%) of 37 hips and 11 (30%) of 37
hips measured at greater than 84˚ at 16-to-18 weeks
and 52 weeks, respectively, developed DJD. For hips
with NorDis angles less than 85˚ at six-to-10 weeks,
27 (69%) of 39 developed DJD. For angles less than
85˚ at 16-to-18 weeks, 12 (92%) of 13 hips developed
DJD, and at one year 15 (100%) of 15 hips had DJD.
Neutral-Positioned Hips Measured During
Compression
Norberg/compression (NorCom) angles (range, 89˚ to
120˚ for all breeds at six-to-52 weeks) were increased
consistently when compared to NorOFA, although
the change was minimal for GHs. No hips developed
DJD that had a NorCom angle greater than 113˚.
However, only 4% of hips measured at six-to-10 and
16-to-18 weeks of age had NorCom angles greater
than 113˚.
July/August 1998, Vol. 34
Comparison of Measurement Techniques and Age
For the 27 hips which developed DJD by one year, the
respective ranges for the three most promising mea-
surement techniques (DI, NorOFA, and NorDis) at
age six-to-10 weeks were 0.31 to 0.77, 79˚ to 99˚, and
63˚ to 84˚. Distraction index measurements varied
somewhat between six-to-10 weeks and 16-to-18
weeks (p of 0.06, ANOVA), but DI measurements did
not vary between six-to-10 weeks and 52 weeks (p of
0.9, ANOVA). There was a trend toward hips becom-
ing tighter between 16 and 52 weeks (p of 0.05,
ANOVA). Both NorOFA and NorDis measurements
varied significantly between six-to-10 weeks and 52
weeks (p of 0.0001, ANOVA). For all evaluated hips
(n=23) which had no DJD by one year, DI did not
vary between eight and 16 weeks, but significant
variation occurred for NorOFA and NorDis measure-
ments between these ages (p less than 0.001, ANOVA).
For 16 GH hips at eight weeks of age, the ranges
for the three measurements were DI of 0.13 to 0.27,
NorOFA of 90˚ to 103˚, and NorDis of 75˚ to 95˚. These
measurements improved significantly at 16-to-18
weeks and 52 weeks (p less than 0.001, ANOVA);
however, the most dramatic improvement occurred
between four and six weeks of age (p less than 0.001,
ANOVA) [Table 1].
Eight GH hips (i.e., the controls) were evaluated
only at four, 24, and 52 weeks of age. Sixteen GH
hips were measured at four, six, eight, 12, 16, 26, and
52 weeks of age. Comparisons of DI, NorOFA, and
NorDis measurements between these two groups were
made to determine if repeated hip manipulation under
anesthesia had any effect on results. There were no
differences in the three ages at which both groups
were measured (p of 0.19 to 0.92, ANOVA).
Comparison of Measurement Techniques and
Degenerative Joint Disease
At six-to-10 weeks of age, no hip with a DI value less
than 0.31 (n=16 hips) or a NorDis angle measurement
greater than 84˚ (n=12 hips) later developed DJD. For
statistical ANOVA, a 50% probability of developing
DJD was predicted at DI values of 0.40 and 0.41 for
ages six-to-10 weeks and 16-to-18 weeks, respec-
tively. Distraction index was somewhat better at pre-
dicting DJD than NorDis, as seen by p values (0.0001
versus 0.0007) and percentage of correct prediction
(78.4% versus 68.6%) in Table 2. At 16-to-18 weeks
of age, the difference between these two methods was
minimal. Nine of 10 hips with DI values greater than
0.61 and all seven hips with NorDis angle measure-
ments less than 75˚ at six-to-10 weeks of age later
developed DJD. A similar trend was found at 16-to-
18 weeks.
A backward elimination procedure with logistic
regression was performed to determine if data from
July/August 1998, Vol. 34
more than one of the six methods (Ortolani’s maneu-
ver, Bardens’ maneuver, distraction index, Norberg
angle, Norberg angle during distraction, and Norberg
angle during compression) of measuring laxity was
useful in predicting DJD at eight, 16, and 52 weeks of
age. Distraction index alone was selected by the back-
ward elimination procedure. Thus, once DI was
known, none of the other methods added significantly
to prediction of DJD occurrence.
Discussion
Both palpation methods and all four radiographic mea-
surement methods used to determine laxity (and there-
fore likelihood of DJD) when applied to one-year-old
hips, were significantly diagnostic as determined by
consensus opinion of radiographic DJD findings at 52
weeks. Both palpation methods (i.e., Ortolani’s ma-
neuver and Bardens’ maneuver) were quite insensi-
tive at six-to-10 weeks (false negatives, 85% and
81%, respectively) and at 16-to-18 weeks (false nega-
tives, 37% and 74%, respectively) for predicting DJD,
even in the hands of an experienced orthopedic sur-
geon. Likewise, subjective assessment of extended-
hip (OFA) radiographs was quite insensitive at
six-to-10 weeks (89% false negative) and at 16-to-18
weeks (56% false negative) for predicting DJD, in
agreement with previous reports. 14,15 It is notable that
although palpation and subjective radiographic meth-
ods were insensitive at these two age brackets, speci-
ficity of these methods was high, as very few
false-positive results were recorded at either six-to-
10 weeks or 16-to-18 weeks of age. When all seven
methods were applied at six-to-10 weeks of age, three
radiographic measurement methods (i.e., DI, NorOFA,
NorDis) were related significantly to the incidence of
DJD at 52 weeks.
Distraction index was statistically the most predic-
tive method for DJD when applied at either six-to-10
weeks or 16-to-18 weeks of age. At six-to-10 weeks
of age, all hips with DIs less than 0.31 were normal at
one year and 81% of hips with DIs in the range of
0.31 to 0.41 were normal at one year. At 16-to-18
weeks, predictability of DI values (in the range of
0.31 to 0.41) for normal hips at one year increased to
93%. This result is similar to the previously reported
88% correct prediction for normal hips in 16-week-
old LRs at DI less than 0.40.14 Prediction of DJD by
DI for puppies 16 weeks of age in this report was
found to be more accurate than previously reported. 14
At an earlier age (six-to-10 weeks) in this study, a DI
greater than 0.60 predicted DJD in 90% of hips, while
a DI greater than 0.70 predicted DJD in 100% of hips.
As an early screening test to detect puppies at
minimal risk for developing DJD, DI appears more
useful than NorOFA, as suggested by others. 14,15 At
six-to-10 weeks of age, many more hips were mea-
Canine Hip Dysplasia 345
sured below the 0.26 DI threshold for DJD than above
the 107˚ NorOFA threshold for DJD (24% versus
0%). Norberg angle measurement during hip distrac-
tion (NorDis), as first reported here, also appears
accurate in predicting DJD, though not with quite as
great a sensitivity as the DI (68.6% and 78.4% cor-
rect, respectively).
Results of this study do not support the concern
that repeated hip palpations or stress radiography may
lead to joint instability. Despite repeating hip palpa-
tion and stress views seven times in GH puppies, no
evidence of DJD or increased laxity was detected
compared to control hips. In fact, GH hips became
significantly tighter over time. This finding in a tight-
hipped breed does not address the possibility that
hips at risk (i.e., lax hips) may be traumatized by
repeated stress radiography, but a similar tendency
for DI scores to decrease (i.e., decreased laxity) be-
tween 16 and 52 weeks of age also was observed in
hips that developed DJD during this study. As all
examinations were performed under fluoroscopic con-
trol, only enough force was applied to visualize sub-
luxation. In cases of significant joint laxity, the
femoral head was observed fluoroscopically to “pop
out” of acetabular alignment with very minor force.
Applying more force resulted in little, if any, addi-
tional subluxation.
A limitation of this study was the statistical neces-
sity to pool data from several breeds, due to the small
number of puppies. As illustrated in Table 1, breeds
at risk for hip dysplasia may fall into a DI range quite
apart from the range measured from a breed (e.g., the
GH) with tight hips. Clinical application of a laxity
index such as DI will require assessment of indi-
vidual breeds in sufficient numbers for statistical
analysis.
It is of interest to note that the mean DI of one-
year-old LR (0.53) and IS (0.46) hips here reported
are almost identical to median DI scores for these
breeds in the PennHIP data base (0.52 and 0.47, re-
spectively). 20 It also is notable that these LR puppies
were from hip dysplasia-positive parents, and the IS
puppies were progeny of OFA-certified “good” par-
ents. Similarity in the mean DIs of these LR and IS
hips is consistent with the report that there has been
no significant decrease in the incidence of hip dyspla-
sia in these two breeds between 1972 and 1990. 3
The presence of DJD was based on the consensus
of four expert readers. Credibility of this assessment
was strengthened by disqualification of any hips upon
which the four readers did not agree and by retrospec-
tive verification of the occurrence of enthesophytes
not visualized on earlier films of the same joints.
Sensitivity of detecting DJD was limited by the fact
that hips were not radiographed beyond 52 weeks of
age. Historically, radiographic signs of hip dysplasia
346 JOURNAL of the American Animal Hospital Association
are reported present in 62% to 80% of affected dogs
at one year of age. 10,16 In a more recent study, DJD
present by three years of age was evident in 32 (94%)
of 34 dogs when radiographed at one year of age. 17
Specificity of enthesophyte findings resulting in a
diagnosis of DJD was limited by absence of histo-
pathological verification. Enthesophytes seen in this
series were typical in appearance to those associated
with coxofemoral DJD 8,12 and were documented as
acquired changes.
This study supports the conclusions of others that
measurement of joint laxity is a sensitive predictor of
DJD, 7,14,17 that a DI less than 0.30 indicates minimal
risk of CHD, and that a DI greater than 0.70 when
applied to puppies at four months 15 or six months 18 of
age makes DJD all but certain. This study also con-
firms the predictability of increased risk of CHD as
the DI increases between 0.30 and 0.70. Results pre-
sented here are in disagreement with a study of 16
German shepherd dog puppies radiographed from
eight weeks of age. In that study, hip laxity was not
sufficiently reliable to use in a predictive sense at
eight weeks of age. 19 This differing result underscores
the opinion that there is breed variation between a
given degree of hip laxity and prediction of DJD.b
In this study, over 50% of hips which developed
DJD by one year were assessed as not being dysplastic
at 16-to-18 weeks of age on subjective radiographic
assessment in the extended-hip (OFA) position. This
finding does not support the OFA report of 91% reli-
ability of that method in puppies three-to-six months
of age. 21 Additional imaging studies in puppies be-
ginning at eight weeks of age presently are underway
using other CHD-susceptible breeds, in order to ad-
dress these differing reports.
Conclusion
In the hands of a trained clinician, a positive
Ortolani’s or Bardens’ sign at six-to-10 weeks or 16-
to-18 weeks of age was an accurate predictor for later
development of DJD. However, false-negative inci-
dence with these palpation methods at both ages was
unacceptable. Prediction of DJD by subjective radio-
graphic assessment of extended-hip (OFA) views at
six-to-10 weeks and at 16 weeks of age also resulted
in a high number of false negatives and cannot be
recommended as a routine screening method.
Development of coxofemoral DJD by 52 weeks of
age was predicted accurately in six- to 10-week-old
LR, IS, and HM puppies by three radiographic mea-
surement methods. Radiographic assessment with hips
in neutral position using a distraction index (PennHIP
method) was the most accurate of two palpation and
five radiographic methods tested. A previously sug-
gested joint-laxity threshold (DI greater than 0.30)
for development of DJD was substantiated, as was a
July/August 1998, Vol. 34
laxity threshold (DI greater than 0.70) above which
DJD appears nearly certain. Even in very tight-hipped
puppies, there is a significant difference in hip radio-
graphic appearance between four and eight weeks of
age, resulting in unacceptable measurement inaccu-
racy at four weeks of age.
a
E.A. Corley, DVM, PhD, President and Executive Director, Orthopedic
Foundation for Animals, Columbia, MO
b
G.K. Smith, VMD, PhD, School of Veterinary Medicine, University of
Pennsylvania, 3800 Spruce Street, Philadelphia, PA
Acknowledgments
This research was supported by a grant from the
American Animal Hospital Association.
The authors are grateful to Drs. E. A. Corley, G. K.
Smith, and L. J. Forrest for their excellent assistance
and consultations and to James Fialkowski and Peter
Crump for their detailed technical assistance.
References
1. Schnelle GB. Some new diseases in the dog. Am Kennel Gaz 1935;52:
25–6.
2. Rendano VT, Ryan G. Canine hip dysplasia evaluation: a positioning and
labelling guide for radiographs to be submitted to the Orthopedic Foun-
dation for Animals. Vet Radiol 1985;26:170–6.
3. Corley EA, Keller GG. Hip dysplasia: a progress report and update.
Orthopedic Foundation for Animals, 1993:3.
4. Smith GK, Biery DN, Gregor TP. New concepts of coxofemoral joint
stability and the development of a clinical stress-radiographic method
for quantitating hip joint laxity in the dog. J Am Vet Med Assoc
1990;196:59–70.
5. Henricson B, Norberg I, Olsson S-E. On the etiology and pathogenesis
of hip dysplasia: a comparative review. J Sm Anim Pract 1966;7:673–87.
6. Bardens JW, Hardwick H. New observations on the diagnosis and cause
of hip dysplasia. Vet Med Sm Anim Clin 1968;63:238–45.
7. Madsen JS, Svalastoga E. Early diagnosis of hip dysplasia—a stress-
radiographic study. Vet Clin Orthop Traum 1995;8:114–7.
8. Riser WH. The dysplastic hip joint: its radiographic and histological
development. J Am Vet Radiol Soc 1973;14:35–50.
9. Chalman JA, Butler HC. Coxofemoral joint laxity and the Ortolani sign.
J Am Anim Hosp Assoc 1985;21:671–6.
10. Corley EA, Keller GG. Hip dysplasia: a guide for dog breeders and
owners. 2nd ed. Columbia, MO: Orthopedic Foundation for Animals,
1989:4.
11. Douglas SW. The Norberg method of assessing hip dysplasia. In:
Williamson HD, Douglas SW, eds. Veterinary radiological interpreta-
tion. 1st ed. Philadelphia: Lea & Febiger, 1970:109.
12. Morgan JP. Canine hip dysplasia: significance of early bone spurring.
Vet Radiol 1987;28:2–5.
13. Hosmer DW, Lemeshow S. Applied logistic regression. New York:
J Wiley and Sons, 1989:64–9.
14. Lust G, Williams AJ, Burton-Wurster N, et al. Joint laxity and its
association with hip dysplasia in Labrador retrievers. Am J Vet Res
1993;54:1990–9.
15. Smith GK, Gregor TP, Rhodes WH, Biery DN. Coxofemoral joint laxity
from distraction radiography and its contemporaneous and prospective
correlation with laxity, subjective score, and evidence of degenerative
joint disease from conventional hip-extended radiographs in dogs.
Am J Vet Res 1993;54:1021–42.
16. Jessen CR, Spurrell FA. Radiographic detection of canine hip dysplasia
in known age groups. Proceed, Am Vet Med Assoc Symposium on Hip
Dysplasia, 1972:93–8.
17. Smith GK, Popovitch CA, Gregor TP, Shofer FS. Evaluation of risk
factors for degenerative joint disease associated with hip dysplasia in
dogs. J Am Vet Med Assoc 1995;206:642–7.
July/August 1998, Vol. 34 Canine Hip Dysplasia 347

18. Flückiger M. Stress radiography for the detection of hip joint laxity in 20. Smith GK. PennHip director. Quarterly breed update. Malvern, PA:
the dog. Proceed, Euro Assoc Vet Diag Imaging Meeting, Berlin, Synbiotics, October 1997:4.
September 1995:30. 21. Corley EA, Keller G, Lattimer JC, Ellersieck MR. Reliability of early
19. Smith GK. Diagnosis of canine hip dysplasia. Proceed, Western Vet radiographic evaluations for canine hip dysplasia obtained from the
Conf, 1995:12–9. standard ventrodorsal radiographic projection. J Am Vet Med Assoc
1997;211:1142–6.
 The Effects of Stains and Investigators
on Assessment of Morphology of
Canine Spermatozoa
Percentage and types of morphological abnormalities found in canine spermatozoa
were evaluated by three investigators using three stains (Giemsa-Wright stain
[Diff-Quik], eosin Y/nigrosin [Hancock], and eosin B/nigrosin [Society for
Theriogenology morphology stain] with conventional light microscopy, compared to
phase contrast microscopy on unstained samples. The percentage of spermatozoa
with abnormal heads, midpieces, and tails varied by technique and by investigator.
Average percentages of morphologically normal spermatozoa were significantly
higher in samples stained with Diff-Quik and samples examined by phase contrast
microscopy than in samples stained with Hancock or Society for Theriogenology
morphology stains. No effect of investigator on the percentage of morphologically
normal spermatozoa was assessed. Results suggest that staining or preparation
technique may alter the morphology of canine spermatozoa artifactually.
J Am Anim Hosp Assoc 1998;34:348–52.

Margaret V. Root Kustritz, Introduction

DVM, PhD
Patricia N. Olson, DVM, PhD
Shirley D. Johnston, DVM, PhD
Teresa K. Root, BS
O positive correlations in the dog between percentage of morphologi-
From the Department of
Small Animal Clinical Sciences,
College of Veterinary Medicine,
University of Minnesota,
1352 Boyd Avenue,
St. Paul, Minnesota 55108.
Morphological defects of spermatozoa may be predictors of fertility.
A positive correlation has been reported between normal morphol-
ogy, acrosomal function, fertilizing capacity of spermatozoa, and
success of in vitro fertilization in humans. 1–5 Morphological abnor-
malities of spermatozoa are associated with decreased fertility in the
bull, 6–11 stallion,12–14 boar, 8,15 ram, 8 and dog. 16–19 Renton, et al.19 and
Plummer, et al.18 described midpiece abnormalities associated with
infertility in the dog. Oettle 17 and Mickelsen, et al. 16 demonstrated
cally normal spermatozoa and fertility rate, and the total number of
morphologically normal spermatozoa and pregnancy rate, respectively.
Morphology of spermatozoa can be assessed using conventional
light microscopy or phase contrast microscopy, with or without stain-
ing. Staining has been shown either to increase or decrease percent-
ages of morphologically normal spermatozoa in the bull, 20–24
stallion, 24,25 boar, 24 ram, 24 buck,24 rabbit, 20 human, 20,26–30 and dog. 31
In one study, eosin B/nigrosin stain (Society for Theriogenology
morphology stain), with osmolality of 135 mOsm and pH of 2.27,
caused a significant increase in the percentage of canine spermatozoa
with bent tails.31
The objective of the study reported herein was to determine whether
the percentages of morphologically normal and abnormal spermato-
zoa evaluated by three investigators were different in stained samples
(using one of three stains) examined with conventional light micros-
copy or in unstained samples examined with phase contrast microscopy.
Materials and Methods
Breeder clients were solicited for inclusion of intact male dogs in this
study. Twenty-three dogs were presented for breeding soundness

348 JOURNAL of the American Animal Hospital Association

July/August 1998, Vol. 34
examination and semen collection; all were included
in the study. The dogs ranged in age from 10 months
to 14 years (mean±standard deviation [SD], 6.2±3.8
yrs) and represented 12 breeds.
Canine semen was collected into a latex artificial
vagina, as described previously, in the absence of a
teaser bitch. 32 Samples and equipment were held at
room temperature. Volume was recorded for each
sample, and then aliquots were removed for evalua-
tion of progressive motility and total number of sper-
matozoa in the ejaculate. Progressive motility was
evaluated immediately; total number of spermatozoa
in each ejaculate was evaluated, and the remainder of
each sample was processed for morphology assess-
ment within four hours of collection. Semen evalua-
tion has been described previously. 32
From each sample, an aliquot of semen was diluted
1:9 with formol-buffered saline and refrigerated for
less than one week at 4˚ C until evaluated by phase
contrast microscopy. The remainder of the undiluted
semen sample then was used to make nine slides,
three of which were stained with a rapid Giemsa-
Wright stain (Diff-Quik),a three of which were stained
with an eosin Y/nigrosin stain (Hancock), b and three
of which were stained with an eosin B/nigrosin stain
(Society for Theriogenology morphology stain).c Mor-
phology specimens were prepared for staining with Diff-
Quik by placing a drop of semen on a glass slide, drawing
it out with a second slide (as for a blood smear), and
allowing it to air dry. The slides were immersed serially
in each of the three Diff-Quik solutions for five minutes,
rinsed, and allowed to air dry. Slides were prepared
for morphology assessment with Hancock or Society
for Theriogenology morphology stain by placing a
drop of semen and a drop of either Hancock or Soci-
ety for Theriogenology morphology stain on one end
of each glass slide. The drops were mixed, and the
resultant mixture was drawn out with another glass
slide. Each slide was allowed to air dry. Stained
slides were held at room temperature pending
evaluation.
A factorial design was used; three investigators
evaluated all samples using each of the four techniques
(i.e., three staining techniques for conventional light
microscopy and phase contrast microscopy). The in-
vestigators were veterinarians with experience in
evaluating canine semen. Stained slides were coded
with random numbers and were examined in random
order by the investigators using oil immersion at
1,000X magnification. One hundred spermatozoa
were examined on each slide. Percentages of morpho-
logically normal sperm and spermatozoa with defects
of the head, midpiece, tail, or combinations were
recorded. All investigators classified morphological
abnormalities according to a descriptive chart pre-
pared jointly. One hundred unstained spermatozoa
Canine Spermatozoa 349
also were evaluated using phase contrast microscopy.
Spermatozoa lying on their sides were not evaluated.
Statistical analysis was performed using multivari-
ate analysis of variance (MANOVA). The data as-
sumed a normal distribution. The influence of
technique, investigator, or both and interaction be-
tween technique and investigator on percentage of
morphologically normal spermatozoa, percentage of
spermatozoa with abnormal heads, percentage with
abnormal midpieces, and percentage with abnormal
tails were assessed, with a p value of less than 0.05
considered significant. Pair-wise comparisons were
made using the least significant difference test.
Results
Semen was collected from the 23 dogs. Mean volume
±SD was 3.2±2.3 ml (range, 1.0 to 10.0 ml). The
percentage of progressively motile sperm averaged
69%±24% (range, 10% to 90%). Total number of
spermatozoa in the ejaculate ranged from 10 million
to 1.7 billion (mean±SD, 334±375 million).
The percentage of spermatozoa that was morpho-
logically normal and the percentage that had various
morphological abnormalities of the head, midpiece,
and tail were assessed by three investigators using the
four described techniques [Tables 1–4]. The most
common morphological abnormalities of the heads of
canine spermatozoa were detached heads, knobbed
acrosomes, and detached acrosomes. Proximal and
distal cytoplasmic droplets and reflex (i.e., bent)
midpieces were the most frequently identified mor-
phological abnormalities of the midpiece. The three
most common morphological abnormalities of the tail
were bent tails, tails tightly coiled over the midpiece,
and proximally coiled tails.
The stain technique used had an effect on the
percentage of morphologically normal spermatozoa
assessed (p of 0.02). When compared to Diff-Quik-
stained samples and unstained samples examined
using phase contrast microscopy, the percentage of
morphologically normal spermatozoa was signifi-
cantly lower in Hancock- and Society for Therio-
genology morphology-stained samples [Table 1].
No effect of the investigator on the percentage of
morphologically normal spermatozoa was assessed
(p of 0.25), and no interaction between investiga-
tor and technique (p greater than 0.25) was
assessed.
A significant interaction of technique and investi-
gator on the percentage of spermatozoa with head
abnormalities was identified (p less than 0.01). One
investigator evaluated a significantly larger number
of spermatozoa as having head abnormalities on only
the Diff-Quik-stained samples compared to the other
investigators [Table 2]. The presence of the interac-
tion precluded further evaluation of the effects of
350 JOURNAL of the American Animal Hospital Association July/August 1998, Vol. 34

Table 1
Percentage of Morphologically Normal Spermatozoa* Assessed by
Four Techniques and Three Investigators in 23 Canine Samples

Techniques
Society for
Theriogenology
Diff-Quik Stain† Hancock Stain Morphology Stain Phase Contrast†
Investigator 1 62 (21) 56 (19) 52 (20) 63 (20)
Investigator 2 70 (19) 60 (22) 54 (23) 64 (19)
Investigator 3 53 (34) 59 (24) 51 (22) 63 (23)

* Numbers displayed are mean percentages with standard deviations in parentheses

†
Percentages of morphologically normal spermatozoa are higher using these techniques (Diff-Quik and phase
contrast) than others (Hancock and Society for Theriogenology morphology stains)

Table 2
Percentages of Spermatozoa with Head Abnormalities* Assessed by
Four Techniques and Three Investigators in 23 Canine Samples

Techniques
Society for
Theriogenology
Diff-Quik Stain Hancock Stain Morphology Stain Phase Contrast
Investigator 1 10 (11) 10 (9) 7 (9) 5 (5)
Investigator 2 8 (12) 14 (16) 14 (11) 6 (7)
Investigator 3† 28 (37) 13 (13) 11 (15) 4 (6)

* Numbers displayed are mean percentages with standard deviations in parentheses

†
Percentages of Diff-Quik-stained spermatozoa with head abnormalities are higher for this investigator; this interaction
precludes further statistical assessment

investigator and technique on the percentage of sper-
matozoa with head abnormalities.
The percentage of spermatozoa with midpiece ab-
normalities was affected significantly by technique,
with a lower percentage assessed in Diff-Quik-stained
samples and a higher percentage identified in un-
stained samples examined using phase contrast mi-
croscopy compared to Hancock- and Society for
Theriogenology morphology-stained samples (p less
than 0.01) [Table 3]. Neither an effect of investigator
on the percentage of midpiece abnormalities (p greater
than 0.25) nor an interaction between investigator
and technique was assessed (p greater than 0.25).
Investigator (p less than 0.01) and technique (p
less than 0.01) had an effect on the percentage of
spermatozoa assessed as having tail abnormalities.
One investigator classified a significantly larger per-
centage of spermatozoa as having tail abnormalities
compared to the evaluations of the other two investi-
gators [Table 4]. When compared to Diff-Quik- and
Hancock-stained samples and unstained samples ex-
amined using phase contrast microscopy, all three
investigators evaluated the percentage of spermato-
zoa assessed with tail abnormalities as being increased
in Society for Theriogenology morphology-stained
samples. No interaction between technique and in-
vestigator was recognized (p of 0.25).
Discussion
Although percentages of normal spermatozoa and of
specific abnormalities of the head, midpiece, and tail
differed significantly by technique, a much less sig-
nificant effect on the percentage of normal spermato-
zoa was assessed. All techniques used may increase
some abnormalities while decreasing others. The ap-
parent increase in a given abnormality could be due
July/August 1998, Vol. 34 Canine Spermatozoa 351

Table 3
Percentages of Spermatozoa with Midpiece Abnormalities* Assessed by
Four Techniques and Three Investigators in 23 Canine Samples

Techniques
Society for
Theriogenology
Diff-Quik Stain† Hancock Stain Morphology Stain Phase Contrast‡
Investigator 1 14 (15) 22 (15) 21 (19) 24 (19)
Investigator 2 13 (9) 21 (13) 17 (16) 25 (18)
Investigator 3 10 (12) 17 (18) 17 (18) 25 (19)

* Numbers displayed are mean percentages with standard deviations in parentheses

†
Percentages of spermatozoa with midpiece abnormalities are lower using this stain (Diff-Quik) than with others
(Hancock and Society for Theriogenology morphology stains)
‡
Percentages of spermatozoa with midpiece abnormalities are higher using this technique (phase contrast) than with
others (Hancock and Society for Theriogenology morphology stains)

Table 4
Percentages of Spermatozoa with Tail Abnormalities* Assessed by
Four Techniques and Three Investigators in 23 Canine Samples

Techniques
Society for
Theriogenology
Diff-Quik Stain Hancock Stain Morphology Stain† Phase Contrast
‡
Investigator 1 14 (36) 16 (13) 23 (14) 10 (7)
Investigator 2 10 (10) 9 (10) 18 (14) 7 (5)
Investigator 3 8 (8) 10 (13) 20 (18) 8 (9)

* Numbers displayed are mean percentages with standard deviations in parentheses

†
Percentages of spermatozoa with tail abnormalities are higher using this technique (Society for Theriogenology
morphology stain) than others (Diff-Quik and Hancock stains and phase contrast microscopy)
‡
Percentages of spermatozoa with tail abnormalities are higher for this investigator compared to the other
investigators

either to accentuation or creation of that defect by
that technique as evidenced in this study by the sig-
nificantly higher percentage of spermatozoa with tail
abnormalities on Society for Theriogenology mor-
phology-stained samples [Table 4]. The majority of
these tail abnormalities were bent tails, suggesting a
mechanism similar to that described by Johnson, et
al., 31 whereby changes in the chemical composition
of the stain induced morphological changes in the
spermatozoa. An apparent decrease in a given abnor-
mality could be due to either a masking of that defect
or the removal of the defect by that technique. For
example, the percentage of midpiece abnormalities
on unstained samples evaluated by phase contrast mi-
croscopy compared to stained samples increased sig-
nificantly [Table 3]. Some samples contained many
spermatozoa with cytoplasmic droplets which were
visible as transparent bubbles on the midpiece when
using phase contrast microscopy but which were de-
flated or absent on the stained samples, presumably
due to processing of the sample.
The investigators agreed on the percentage of mor-
phologically normal spermatozoa more uniformly than
on abnormal spermatozoa. In a study comparing vis-
ual assessment with computer-assisted assessment of
morphology of human spermatozoa, the percentage of
morphologically normal spermatozoa was the only
parameter classified by both methods with equal pre-
cision. 33 In this study, differences in observed per-
centages of morphological abnormalities were great,
352 JOURNAL of the American Animal Hospital Association
despite review of and agreement on definition of ab- 16.
normal forms. The significant effect of investigator
on the percentage of abnormalities noted highlights 17.
the need for a standardized nomenclature for mor-
18.
phology assessment.
Conclusion 19.
The most reliable measure of morphology of canine
20.
spermatozoa between investigators in this study is
percentage of morphologically normal spermatozoa. 21.
Clinicians should be aware that the staining or prepa-
ration technique used may alter the morphology of 22.
canine spermatozoa artifactually and that consistency
of technique is crucial for comparison of morphology
23.
samples within or between animals.
a 24.
Diff-Quik; Scientific Products, Columbia, MD
b Universitat Munchen, German Federal Republic, 1986.
Hancock; Lane Manufacturing, Denver, CO
c 25.
Modified Blom’s; Society for Theriogenology, Lane Manufacturing,
Denver, CO
26.
References 27.
1. Enginsu ME, Dumoulin JCM, Pieters MHEC, Evers JLH, Geraedts PM.
Predictive value of morphologically normal sperm concentration in the
medium for in-vitro fertilization. Int J Androl 1993;16:113–20. 28.
2. Fukuda M, Morales P, Overstreet JW. Acrosomal function of human
spermatozoa with normal and abnormal head morphology. Gamete Res
1989;24:59–65. 29.
3. Grow DR, Oehninger S, Seltman HJ, et al. Sperm morphology as
diagnosed by strict criteria: probing the impact of teratozoospermia
on fertilization rate and pregnancy outcome in a large in vitro fertiliza- 30.
tion population. Fert Steril 1994;62:559–67.
4. Kruger TF, DuToit TC, Franken DR, et al. A new computerized method
of reading sperm morphology (strict criteria) is as efficient as
technician reading. Fert Steril 1993;59:202–9. 31.
5. Kruger TF, Menkveld R, Stander FSH, et al. Sperm morphologic fea-
tures as a prognostic factor in in vitro fertilization. Fert Steril
1986;46:1118–23. 32.
6. Andersson M, Vierula M, Alanko M. Three types of acrosomal aberra-
tions of bull spermatozoa and their relation to fertility. Acta Vet Scand 33.
1990;31:175–9.
7. Foote RH, Hough SR, Johnson LA, Kaproth M. Electron microscopy and
pedigree study in an Aryshire bull with tail-stump sperm defects.
Vet Rec 1992;130:578–9.
8. Hancock JL. The morphologic characteristics of spermatozoa and
fertility. Int J Fertil 1959;4:347–59.
9. Peet RL, Mullins KR. Sterility in a poll Hereford bull associated with
the “tail stump” sperm defect. Aust Vet J 1991;68:245.
10. Peet RL, Kluck P, McCarthy M. Infertility in 2 Murray Grey bulls
associated with abaxial and swollen midpiece sperm defects. Aust Vet J
1988;65:359–60.
11. Williams WW, Savage A. Observations on the seminal micropathology
of bulls. Cornell Vet 1925;15:353–74.
12. Held JP, Prater P, Stettler M. Spermatozoal head defect as a cause of
infertility in a stallion. J Am Vet Med Assoc 1991;199:1760–1.
13. Jasko DJ, Lein DH, Foote RH. Determination of the relationship be-
tween sperm morphologic classifications and fertility in stallions: 66
cases (1987–1988). J Am Vet Med Assoc 1990;197:389–93.
14. Jasko DJ, Little TV, Lein DH, Foote RH. Comparison of spermatozoal
movement and semen characteristics with fertility in stallions: 64 cases
(1987–1988). J Am Vet Med Assoc 1992;200:979–85.
15. Bach VS, Neundorf P, Stemmler KH, Mudra K, Ueckert H. Amount and
variation of abnormal sperms of boar. Monatshefte fur Vet Med
1982;37:463–7.
July/August 1998, Vol. 34
Mickelsen WD, Memon MA, Anderson PB, Freeman DA. The relation-
ship of semen quality to pregnancy rate and litter size following artificial
insemination in the bitch. Theriogenology 1993;39:553–60.
Oettle EE. Sperm morphology and fertility in the dog. J Rep Fert
1993;Suppl. 47:257–60.
Plummer JM, Watson PF, Allen WE. A spermatozoal midpiece abnor-
mality associated with infertility in a Lhasa apso dog. J Sm Anim Pract
1987;28:743–51.
Renton JP, Harvey MJA, Harker S. A spermatozoal abnormality in dogs
related to infertility. Vet Rec 1986;118:429–30.
Drevius LO. Spiralization in tails of mammalian spermatozoa in hypo-
tonic media. Nature 1963;197:1123–4.
Harasymowycz J, Ball L, Seidel GE. Evaluation of bovine spermatozoal
morphologic features after staining or fixation. Am J Vet Res
1976;37:1053–7.
Salisbury GW, Willett EL, Seligman J. The effect of the method of
making semen smears upon the number of morphologically abnormal
spermatozoa. J Anim Sci 1942;1:199–205.
Sekoni VO, Gustafsson BK, Mather EC. Influence of wet fixation,
staining techniques, and storage time on bull sperm morphology.
Nord Vet Med 1981;33:161–6.
Wurgau T. The significance of tertiary anomalies for the evaluation of
sperm morphology. Thesis: Tierarztliche Fakultat, Ludwig Maximilians
Oetjen M. Use of different acrosome stains for evaluating the quality of
fresh and frozen horse semen. Thesis: Tierarztliche Hochschule
Hannover, German Federal Republic, 1988.
Ali JI, Grimes EM. Sperm morphology: unstained and stained smears in
fertile and infertile men. Arch Androl 1989;22:191–5.
Bornman MS, Sevenster CB, DeMilander C, Otto BS, Olivier I. The
effect of semen processing on sperm morphology. Andrologia
1989;21:117–9.
Cameron RDA. Semen collection and evaluation in the ram. The prepa-
ration of spermatozoa for morphological examination. Aust Vet J
1977;53:384–6.
Meschede D, Keck C, Zander M, Cooper TG, Yeung CH, Nieschlag E.
Influence of three different preparation techniques on the results of
human sperm morphology analysis. Int J Androl 1993;16:362–9.
Michael AY, Drejer JO, Bagger PV, Detlefsen GU, Stakemann G.
Complete staining of human spermatozoa and immature germ cells
combined with phase contrast microscopy. Arch Androl 1987;
19:217–21.
Johnson C, Jacobs J, Walker R. Diagnosis and control of Brucella canis
in kennel situations. Morphology-stain induced spermatozoal abnor-
malities. In: Proceed, Society for Theriogenology, 1991:236–9.
Root MV, Johnston SD. Basics for a complete reproductive examination
of the male dog. Vet Med and Surg 1994;9:41–5.
Wang C, Leung A, Tsoi W, et al. Computer-assisted assessment of
human sperm morphology: comparison with visual assessment.
Fert Steril 1991;55:983–8.