Exocrine pancreatic insufficiency as an end stage of pancreatitis in four dogs

Chronic pancreatitis is a common cause of exocrine pancreatic insufficiency (EPI) in humans and cats but is rarely recognised in dogs in which pancreatic acinar atrophy (PAA) is reportedly more common. This paper describes four dogs which developed EPI secondary to pancreatitis. Two of the dogs also had diabetes mellitus which developed before EPI. One diabetic dog had concurrent hyperadrenocorticism and was euthanased five months after presentation; the other diabetic dog died 48 months after diagnosis. The remaining dogs were alive 78 and 57 months after diagnosis. The number of affected dogs was comparable to the number of cases of presumed PAA seen over the same time period in the same institution. Chronic pancreatitis may be a more common cause of EPI in dogs than previously assumed and may be under-recognised because of difficulties in diagnosis. The relative importance of chronic pancreatitis as a cause of canine diabetes mellitus remains to be ascertained.     

Clinical outcome in 23 dogs with exocrine pancreatic carcinoma

Exocrine pancreatic carcinoma is uncommon in the dog and the veterinary literature surrounding the disease is minimal. Twenty‐three cases of canine exocrine pancreatic carcinoma were reviewed in a retrospective manner to obtain information on clinical presentation, behaviour and survival associated with the disease. Presenting clinical signs were nonspecific and included anorexia, lethargy, vomiting and abdominal pain. The overall median survival time was only 1 day but was confounded by the large number of dogs that were euthanized shortly after diagnosis. Metastatic disease was detected in 78% of cases at the time of diagnosis, attesting to the aggressive nature of the disease. Neither lymph node metastasis, tumour size nor tumour location had an impact on overall survival. Only one patient was a previous diabetic who is contrary to reports of the disease in people and felines. This retrospective study reaffirms the need for early detection measures to optimize disease control. However, the benefits of therapy with surgery or radiation and adjuvant chemotherapy remain to be elucidated in dogs with exocrine pancreatic carcinoma.     

Cutaneous plasmacytomas with amyloid in six dogs.

Cutaneous plasmacytomas associated with local deposition of amyloid were diagnosed by light microscopy in a series of six older dogs (mean age 10.7 years) consisting of two Cocker Spaniels, a Poodle, a Weimeraner, and two mixed-breed dogs. The neoplasms occurred on the digits (2 dogs), forelimb (2 dogs), lip (1 dog), and ear (1 dog). In most cases, groups of neoplastic plasma cells were widely separated by large homogeneous islands of amyloid. The neoplastic cells had characteristic plasmacytoid features, but the degree of pleomorphism varied greatly between different neoplasms. In four of the six tumors, the diagnosis of plasmacytoma was confirmed by the demonstration of a monoclonal plasma cell population using immunofluorescent staining for anti-canine immunoglobulins. In these tumors, the neoplastic cells reacted with only one class of immunoglobulins (IgG). The amyloid did not react with any of the reagents used. The suspicion that the amyloid was of immunoglobulin origin (primary amyloid) was supported by its retention of birefringence under polarized light after treatment with potassium permanganate and staining with Congo red.     

Serum lipase activities and pancreatic lipase immunoreactivity concentrations in dogs with exocrine pancreatic insufficiency

OBJECTIVE: To determine serum lipase activities and pancreatic lipase immunoreactivity (PLI) concentrations in dogs with exocrine pancreatic insufficiency (EPI). ANIMALS: 74 healthy dogs and 25 dogs with EPI. PROCEDURES: A diagnosis of EPI was made on the basis of clinical signs, low serum trypsin like immunoreactivity (TLI) concentration, and response to treatment with enzyme replacement. Median values for fasting serum lipase activity and serum PLI concentrations were compared between the 2 groups with a Mann-Whitney U test. RESULTS: Median fasting serum lipase activity was not significantly different between dogs with EPI (366.0 U/L) and healthy dogs (294.5 U/L), and only 1 dog with EPI had a serum lipase activity less than the lower limit of the reference range. Median serum PLI concentration was significantly lower in dogs with EPI (0.1 microg/L) than in healthy dogs (16.3 microg/L). All dogs with EPI had serum PLI concentrations less than the lower limit of the reference range. CONCLUSION AND CLINICAL RELEVANCE: Serum lipase activity is not limited to the exocrine pancreas in origin, whereas serum PLI is derived only from the exocrine pancreas. Unlike in serum TLI concentrations, there was a small degree of overlap in serum PLI concentrations between healthy dogs and dogs with EPI. Serum TLI concentration remains the test of choice for diagnosis of EPI.     

Zollinger-Ellison syndrome in three dogs

The main clinical signs of three dogs with Zollinger-Ellison syndrome were vomiting, diarrhoea, poor appetite and weight loss. The diagnosis was confirmed by histological examination and by gastrin immunocytochemistry. Gastrin was extracted from pancreatic tumours of two dogs. Gastrin-component III predominated in one dog while gastrin-component II and gastrin-component III were demonstrated in almost equal amounts in the other dog. In one dog serum gastrin concentration was high. Postmortem examination revealed pancreatic tumours in all three dogs and metastases in the regional lymph nodes and liver in two. The pancreatic tumours contained three patterns of growth: solid, trabecular and acinar. Electron microscopy of liver metastases showed cells with secretory granules. In all three dogs there was an erosive oesophagitis and thick gastric mucosa caused mainly by glandular proliferation. Two dogs had erosions and ulcers in the duodenum, one also in the first part of the jejunum. Villous atrophy and cellular infiltration of the duodenal mucosa were found in all dogs.     

Pancreatic abscess in dogs: six cases (1978-1986)

Pancreatic abscess was diagnosed by exploratory celiotomy in 6 dogs. The most common clinical signs included acute onset of lethargy (n = 5), anorexia (n = 6), vomiting (n = 5), and diarrhea (n = 2). Physical examination revealed pain response to abdominal palpation (n = 5), depression (n = 5), icterus (n = 3), fever (n = 3), and cranial abdominal mass (n = 2). Consistent preoperative clinicopathologic abnormalities included leukocytosis with left shift, observance of toxic neutrophils on the blood smear, hyperlipasemia, hyperamylasemia, hyperbilirubinemia, and increased serum alkaline phosphatase activity. In 5 of 6 dogs, abdominal radiography revealed increased soft tissue density in the cranial portion of the abdomen. Ultrasonography performed on 4 dogs confirmed pancreatic mass. In all dogs, exploratory celiotomy revealed a cavitary pancreatic mass that contained sterile, mucopurulent material. Histopathologic diagnoses included acute necrotizing or chronic-active pancreatitis and steatitis. Two dogs were euthanatized at the time of diagnosis, and the remaining 4 were treated by use of pancreatic debridement(s), open abdominal drainage, and intensive administration of fluids and antibiotics. One dog was euthanatized 4 days after surgery, because of progressive pancreatic abscessation. Three dogs recovered and were discharged.     

Histologic assessment and grading of the exocrine pancreas in the dog.

Histologic grading schemes for canine inflammatory conditions are sparse, and in the case of the canine pancreas, have not been previously described. In a previous study, we determined that histologic lesions of the exocrine pancreas occurred much more frequently than gross lesions. The intention of the current study was to develop a histologic grading scheme for nonneoplastic lesions following extensive assessment of the exocrine pancreas from dogs presented for necropsy examination. The parameters of the proposed scheme include neutrophilic inflammation, lymphocytic inflammation, pancreatic necrosis, pancreatic fat necrosis, edema, fibrosis, atrophy, and hyperplastic nodules. In this case series, the most common lesion was pancreatic hyperplastic nodules (80.2%), followed by lymphocytic inflammation (52.5%), fibrosis (49.5%), atrophy (46.5%), neutrophilic inflammation (31.7%), pancreatic fat necrosis (25.7%), pancreatic necrosis (16.8%), and edema (9.9%). Only 8 of the 101 animals had no evidence of any of the lesions in any of the sections examined. Fibrosis, atrophy, and/or lymphocytic infiltration most commonly accompanied nodules. Neutrophilic inflammation, when present, was often associated with necrosis (pancreatic necrosis, pancreatic fat necrosis, or both) and occasionally with hyperplastic nodules. The utilization of a grading scheme for exocrine pancreatic lesions will be useful in advancing the classification of exocrine pancreatic disease in the dog, which may lead to multicenter studies of exocrine pancreatic disorders in the dog and in other species.     

Gross, histologic, cytochemical, and immunocytochemical study of medullary thyroid carcinoma in sixteen dogs

The gross, histomorphologic, cytochemical, and immunocytochemical findings in 16 dogs with medullary thyroid carcinoma were evaluated. Grossly, the neoplasms were encapsulated, firm, lobulated, and grey-white to tan. The typical histologic pattern was groups or sheets of round to polygonal cells with fibrovascular stroma, which was thickened and hyalinized in places. Variants of clear cell (two dogs), giant cell (one dog), and oxyphil cell (one dog) types were also seen. In all 16 dogs, Grimelius-stained sections of the neoplasms revealed intracytoplasmic silver granules; ten tumors contained amyloid and four contained mucin. Immunohistochemically, the neoplasms reacted to AE1/AE3 (n = 13), S-100 protein (n = 5), neuron specific enolase (n = 14), synaptophysin (n = 11), calcitonin (n = 16), somatostatin (n = 4), gastrin (n = 7), and serotonin (n = 6). Only one neoplasm was positive for vimentin. None of the neoplasms reacted to antibodies for neurofilaments, thyroglobulin, insulin, glucagon, or adrenocorticotrophic hormone. Eleven neoplasms contained multiple (two to four) peptides, in various combinations. It was concluded that in dogs, gross and histologic features can be used to distinguish medullary thyroid carcinoma from other thyroid malignancies. Cytochemical and immunocytochemical studies with neuron specific enolase, synaptophysin, and calcitonin can be used to establish the diagnosis of medullary thyroid carcinoma in dogs.     

Diagnosis of canine exocrine pancreatic insufficiency by the assay of serum trypsin-like immunoreactivity

A radioimmunoassay for canine serum trypsin-like immunoreactivity (TLI) has been developed and evaluated for use in the diagnosis of exocrine pancreatic insufficiency (EPI). The maximum fasting TLI concentration in 14 dogs with EPI was 1.8 μg/l, compared with a minimum value of 7.0 μg/l in a control group of 75 dogs. The measurement of serum TLI therefore provides a sensitive test for the diagnosis of EPI in the dog.     

Granular cell tumor of the canine central nervous system: two cases.

Although pure granular cell tumors have been reported in various sites in the dog, only one tumor has been reported in the central nervous system. Two dogs presented with neurologic signs had brain lesions detected by magnetic resonance imaging in the area of the olfactory bulbs and frontal cortex. In both dogs, a clinical diagnosis of a granular cell tumor was made from tissues obtained from stereotactic biopsies guided by computed tomography. Surgical removal of the tumors was followed by histopathologic, ultrastructural, and immunocytochemical characterization. Although not conclusive, these studies indicated that the granular cells were not of leucocyte origin but may have been derived from the meninges. One dog died 12 months after surgery, and the other was alive 4 months later.     

Oral bleeding associated with pancreatic enzyme supplementation in three dogs with exocrine pancreatic insufficiency

Three dogs with exocrine pancreatic insufficiency developed oral bleeding during treatment with pancreatic enzyme supplements. According to the owners of the dogs, bleeding from the oral cavity developed during or shortly after consumption of meals containing the pancreatic enzyme supplement. Oral bleeding stopped in all dogs when owners reduced the dose of the pancreatic enzyme supplement. In 2 dogs, the decrease in the dose of the pancreatic enzyme supplement did not affect fecal consistency. However, in the third dog, the decrease in dose led to a recurrence of clinical signs. Findings in these dogs suggest that high doses of pancreatic enzyme supplements can cause oral bleeding in dogs with pancreatic insufficiency, but that oral bleeding can be successfully managed by dose reduction in most dogs.     

Immunocytochemical detection of amylase, carboxypeptidase A, carcinoembryonic antigen and alpha 1-antitrypsin in carcinomas of the exocrine pancreas of the dog.

The immunocytochemical detection of amylase, carboxypeptidase A, alpha 1-antitrypsin, carcinoembryonic antigen (CEA) and keratin in normal canine pancreatic tissue and in carcinomas of the exocrine pancreas of the dog is described. In the normal pancreas, the acinar cells contain amylase, carboxypeptidase and alpha 1-antitrypsin. The pancreatic ducts react with the antikeratin antibody. Twelve out of 14 pancreatic exocrine carcinomas showed immunoreaction with antiamylase antibody, and 10 with anticarboxypeptidase antibody. Five neoplasms reacted with anti-CEA antibody and three with the anti-alpha 1-antitrypsin antibody. It was not possible to find any systematic difference in the immunocytochemical profiles of acinar, tubular and undifferentiated carcinomas. These results indicate that immunocytochemical marking of amylase and carboxypeptidase is of value in the diagnosis of pancreatic neoplasms in the dog, especially if metastasis is the only material available for study and the tumour does not show any diagnostic feature on routine light microscope preparations.     

Description of the use of contrast‐enhanced ultrasonography in four dogs with pancreatic tumours

Canine pancreatic tumours are rare compared to human medicine and the detection and differentiation of pancreatic neoplasia is challenging with B‐mode ultrasonography, which often leads to late clinical diagnosis and poor prognosis. This case report describes the findings of contrast‐enhanced ultrasonography in four dogs with pancreatic adenocarcinoma or insulinoma. B‐mode ultrasonography of the pancreas revealed a hypoechoic nodule in three dogs and heterogenous tissue in one dog. Contrast‐enhanced ultrasonography was able to differentiate between two tumour types: adenocarcinomas showed hypoechoic and hypovascular lesions, whereas insulinomas showed uniformly hypervascular lesions. Contrast‐enhanced ultrasonography findings were confirmed by cytology and/or histopathology. The results demonstrated that contrast‐enhanced ultrasonography was able to establish different enhancement patterns between exocrine (adenocarcinoma) and endocrine (insulinoma) tumours in dogs .     

Evaluation of Fecal Elastase and Serum Cholecystokinin in Dogs with a False Positive Fecal Elastase Test

Background: An assay for the measurement of pancreatic elastase in dog feces has been introduced. Hypothesis/Objectives: The goal of this study was to evaluate the rate of false‐positive fecal‐elastase test results in dogs with suspected exocrine pancreatic insufficiency (EPI) and to assess serum cholecystokinin (CCK) concentrations in dogs with a false positive fecal elastase test result. Animals: Twenty‐six fecal and serum samples from dogs suspected of EPI, for which samples had been submitted to a commercial laboratory (Vet Med Labor) for analysis. Methods: Prospective study. Serum trypsin‐like immunoreactivity (TLI) was measured in 26 dogs with a decreased fecal elastase concentration of <10 μg/g feces. Serum CCK concentrations were measured in 21 of these dogs. Results: Of 26 dogs with a decreased fecal elastase concentration, 6 (23%) had serum TLI concentrations within or above the reference range. Serum CCK concentrations were significantly higher in dogs with a true positive fecal elastase test result (median: 1.1 pmol/L; range: 0.1–3.3 pmol/L) than in those with a false positive fecal elastase test result (median: 0.1 pmol/L; range: 0.1–0.9 pmol/L; P value = .0163). Conclusions and Clinical Importance: The rate of false positive fecal elastase test results was high in this group of dogs, suggesting that diagnosis of EPI must be confirmed by other means. The decreased CCK concentration in dogs with a false positive fecal elastase test result could suggest that false positive results are because of decreased stimulation of exocrine pancreatic function caused by other conditions.     

Hyperadrenocorticism associated with excessive sex hormone production by an adrenocortical tumor in two dogs.

An 11-year-old spayed female Labrador Retriever and a 9-year-old castrated male miniature Poodle were evaluated because of clinical signs of hyperadrenocorticism. Cortisol testing did not support a diagnosis of hypercortisolemia in either dog; however, imaging studies revealed unilateral adrenal tumors in both dogs. Serum concentrations of 17-hydroxyprogesterone, progesterone, and estradiol were high in both dogs, and androstenedione concentrations were also high in 1 dog. It is suspected that sex hormone secretion by the adrenal tumors in these dogs resulted in clinical signs of hyperadrenocorticism. Clinical signs and hormonal abnormalities resolved in the male dog after surgical resection of the tumor. There was no improvement in clinical signs after treatment with mitotane in the female dog, which died 2 months after diagnosis. Histologic evaluation confirmed the presence of adrenocortical carcinoma in both dogs.     

Evaluation of piroxicam for the treatment of oral squamous cell carcinoma in dogs

OBJECTIVE: To evaluate the use of piroxicam for the treatment of oral squamous cell carcinoma in dogs. DESIGN: Prospective case series. ANIMALS: 17 dogs with measurable oral squamous cell carcinoma. PROCEDURE: Dogs were treated with piroxicam at a dosage of 0.3 mg/kg (0.14 mg/lb) of body weight, PO, every 24 hours until progressive disease or unacceptable signs of toxicosis developed or the dog died. RESULTS: One dog had a complete remission (maxillary tumor), and 2 dogs had partial remissions (lingual tumor and tonsillar tumor). An additional 5 dogs had stable disease, including 1 with a maxillary tumor, 2 with mandibular tumors, and 2 with tonsillar tumors. Variables associated with tumor response were not identified. Median and mean times to failure for the 3 dogs that had a remission were 180 and 223 days, respectively. Median and mean times to failure for the 5 dogs with stable disease were 102 and 223 days, respectively. Time to failure was positively associated with tumor response and negatively associated with tumor size. One dog had mild adverse gastrointestinal tract effects that resolved with the addition of misoprostol to the treatment regimen. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that piroxicam may be useful in the treatment of dogs with oral squamous cell carcinoma; response rate was similar to that reported for other cytotoxic treatments. Larger-scale studies are warranted to determine what role piroxicam may have, alone or in combination with other treatments, for the treatment of dogs with oral squamous cell carcinoma.     

Sensitivity and specificity of canine serum total amylase and isoamylase activity determinations.

Serum isoamylases were determined prospectively in dogs with pancreatic and extrapancreatic diseases. Mean serum isoamylase determinations were significantly different (p less than 0.05) between normal dogs and dogs with pancreatitis and exocrine pancreatic insufficiency. The sensitivity of serum isoamylase determination exceeded that of total amylase activity for the diagnosis of pancreatitis. Serum isoamylase determinations were less influenced by extrapancreatic diseases compared to total amylase activity when used in the diagnosis of pancreatic disease. Neither serum isoamylase determination nor total amylase activity had adequate sensitivity to support their use in the diagnosis of exocrine pancreatic insufficiency. There were significant (p less than 0.05) linear correlations between isoamylase determinations, total amylase activity, and trypsin-like immunoreactivity concentration.     

Autoantibodies to pancreatic islet cells in canine diabetes mellitus

Indirect immunofluorescence on normal canine pancreatic tissue fixed in Bouin's solution was used to detect islet cell antibodies in dogs with diabetes mellitus, other endocrine diseases, and pancreatitis. 18 of 25 dogs with diabetes mellitus alone, 2 of 8 dogs with diabetes mellitus and concurrent pancreatitis, and 2 of 2 dogs with diabetes mellitus and concurrent pancreatic exocrine insufficiency were positive for autoantibody. 2 of 12 dogs with hypoadrenocorticism, 3 of 6 dogs with hyperadrenocorticism, 6 of 28 dogs with hypothyroidism and one of 19 dogs with pancreatitis alone were also antibody positive. None of 20 healthy dogs or 20 dogs with disorders other than those of the pancreas or endocrine organs were antibody positive. Islet cell antibodies were demonstrated in dogs with diabetes mellitus and other endocrine disorders. The possibility of autoimmune involvement in the development of diabetes mellitus in the dog should be considered.     

Canine pancreatic endocrine tumors: immunohistochemical analysis of hormone content and amyloid

Thirty-one primary canine pancreatic endocrine tumors and their metastases were studied histologically and immunohistochemically for the presence of insulin, glucagon, somatostatin, pancreatic polypeptide (PP), gastrin, and adrenocorticotrophic hormone (ACTH). Tumors were also evaluated for the presence of amyloid. The cytoarchitectural pattern of 25 of 31 primary tumors was predominantly solid, whereas three tumors were mostly glandular, two were unclassified, and one had a gyriform pattern. Cells with insulin immunoreactivity were found in 30 of 31 tumors and were found in all cases in which there was clinical evidence of inappropriate insulin secretion. Insulin was the only hormone demonstrable in three of the 30 tumors, but cells immunoreactive for other hormones were also present in various combinations in most tumors [i.e., glucagon (13 of 30), somatostatin (17 of 30), PP (25 of 30), and gastrin (2 of 30)]. One tumor contained only cells with glucagon and PP immunoreactivity. Amyloid was found in ten of 31 primary tumors but was not detected in metastases. Cells with insulin immunoreactivity were the only cell type consistently present in tumors containing amyloid. Amyloid deposits did not immunoreact with any of the antisera. Seventeen of 31 dogs had metastasis of the pancreatic endocrine tumor to regional lymph nodes, liver, or both. All metastases available for study (15 of 17) contained cells with insulin immunoreactivity and some contained cells with PP or somatostatin immunoreactivity. No statistically significant (P greater than 0.05) differences in tendency to metastasize were found when pancreatic endocrine tumors were compared by region of origin, cytoarchitectural pattern, presence of amyloid, or by number of hormones contained within the tumor.     

Streptozocin for treatment of pancreatic islet cell tumors in dogs: 17 cases (1989-1999)

OBJECTIVE: To determine toxic effects of streptozocin given in combination with a diuresis protocol in dogs and establish whether streptozocin is efficacious in treatment of pancreatic islet cell tumors in dogs. DESIGN: Retrospective study. ANIMALS: 17 dogs. PROCEDURE: Medical records were reviewed to obtain information regarding signalment, tumor stage and staging tests performed, number of streptozocin treatments, adverse effects, results of biochemical and hematologic monitoring during streptozocin treatment, tumor dimensions, duration of normoglycemia, and date of death, when applicable. Dogs were compared with a historical control group of 15 dogs treated surgically and medically. RESULTS: 58 treatments were administered to the 17 dogs. Only 1 dog developed azotemia. Serum alanine aminotransferase activity increased in some dogs but decreased when treatment was discontinued. Hematologic toxicoses were rare. Vomiting during administration was uncommon but occasionally severe. Two dogs developed diabetes mellitus after receiving 5 doses. Median duration of normoglycemia for 14 dogs with stage-II or -III insulinoma treated with streptozocin was 163 days (95% confidence interval, 16 to 309 days), which was not significantly different from that for the control dogs (90 days; 95% confidence interval, 0 to 426 days). Two dogs had rapid resolution of paraneoplastic peripheral neuropathy, and 2 others had measurable reductions in tumor size. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that streptozocin can be administered safely to dogs at a dosage of 500 mg/m2, IV, every 3 weeks when combined with a protocol for induction of diuresis and may be efficacious in the treatment of dogs with metastatic pancreatic islet cell tumors.