Oral ulceration and bleeding associated with pancreatic enzyme supplementation in a German shepherd with pancreatic acinar atrophy

A 20-month-old German shepherd with primary pancreatic acinar atrophy and exocrine pancreatic insufficiency that was treated with pancreatic enzyme supplementation, vitamin B12, and cimetidine developed oral bleeding. Following discontinuation of the cimetidine, increased preincubation of the enzymes with the food, and symptomatic therapy for the ulceration, the dog's condition improved.     

Subclinical exocrine pancreatic insufficiency in dogs

OBJECTIVE: To study progression of autoimmune-mediated atrophic lymphocytic pancreatitis from the subclinical to the clinical phase (exocrine pancreatic insufficiency [EPI]) and determine whether progression of the disease could be halted by treatment with immunosuppressive drugs. DESIGN: Randomized controlled trial. ANIMALS: 20 dogs with subclinical EPI. PROCEDURE: Diagnosis of subclinical EPI was determined on the basis of repeatedly low serum trypsin like-immunoreactivity (TLI) in dogs with no signs of EPI. Laparotomy was performed on 12 dogs with partial acinar atrophy and atrophic lymphocytic pancreatitis. A treatment group (7 dogs) received an immunosuppressive drug (azathioprine) for 9 to 18 months, and a nontreatment group (13) received no medication. RESULTS: During the subclinical phase, serum TLI was repeatedly low (< 5.0 microg/L). Although a few dogs had nonspecific gastrointestinal tract signs, they did not need diet supplementation with enzymes. While receiving immunosuppressive medication, treated dogs had no clinical signs of EPI, but within 2 to 6 months after treatment was stopped, 2 dogs had signs of EPI, and diet supplementation with enzymes was started. Five of the 13 untreated dogs needed diet supplementation with enzymes within 6 to 46 months. During follow-up of 1 to 6 years, 3 of the 7 treated dogs and 8 of the 13 untreated dogs did not need continuous diet supplementation with enzymes. CONCLUSIONS AND CLINICAL RELEVANCE: Progression of atrophic lymphocytic pancreatitis varied widely. The subclinical phase may last for years and sometimes for life. The value of early treatment with an immunosuppressive drug was questionable and, because of the slow natural progression of the disease, cannot be recommended.     

Serum isoamylase values in normal dogs and dogs with exocrine pancreatic insufficiency

Estimations were made of the serum isoamylase values of normal dogs and of dogs with confirmed exocrine pancreatic insufficiency. A statistically significant difference was demonstrated between the two groups in respect of the values of one of the isoamylase fractions measured. Further study has confirmed that canine salivary tissue lacks amylase activity and that the source of the isoamylase fractions was the pancreas.This knowledge has potential value in the diagnosis of canine exocrine pancreatic insufficiency.     

Bacterial overgrowth in the duodenum of dogs with exocrine pancreatic insufficiency

Bacterial overgrowth (greater than 10(5) colony-forming units/ml duodenal juice) in the duodenum was demonstrated in 8 of 11 dogs with exocrine pancreatic insufficiency (EPI). In 4 of these 8 dogs, the overgrowth included large numbers (greater than 10(4) colony-forming units/ml) of obligate anaerobic bacteria and was associated with decreased activities of several brush border marker enzymes and, in 2 dogs, with partial villous atrophy in the jejunum. Changes in the jejunal mucosa of the remaining dogs (with either no overgrowth or overgrowth of aerobic bacteria alone) were characterized by increased activities of some brush border disaccharides and of lysosomal hydrolases. One dog was euthanatized without treatment, at the owner's request. The response of 4 of the remaining 10 dogs treated with enzyme replacement alone was poor or suboptimal, and all of these 4 dogs had bacterial overgrowth. One of these dogs had an excellent clinical response when also given oxytetracycline orally for 14 days, but the other 3 dogs did not improve further in response to the same treatment. It was concluded that bacterial overgrowth in the duodenum is common in dogs with EPI and that, when such overgrowth includes large numbers of obligate anaerobes, there may be associated biochemical and morphologic abnormalities in jejunal mucosa. Functional disturbances related to abnormal intestinal microflora may be responsible for the failure of some dogs with EPI to respond fully to oral pancreatic enzyme supplementation without antibiotic therapy.     

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.     

Effect of exocrine pancreatic insufficiency on cobalamin absorption in dogs

The possibility that the canine pancreas might have an important role in the physiologic absorption of cobalamin (vitamin B12) has been explored by determining the effect of exocrine pancreatic insufficiency on cobalamin absorption and by examining the subsequent influence of bovine pancreatic enzymes and canine pancreatic juice. Exocrine pancreatic insufficiency was induced by ligation of pancreatic ducts and confirmed by indirect assessment of exocrine pancreatic function. Cobalamin absorption was determined by oral administration of cyano[58Co]cobalamin and quantitation of radioactivity in blood, urine, and feces during 48 hours. Pancreatic duct ligation resulted in a significant (P less than 0.001) decrease in cobalamin absorption, which was not restored by oral administration of bovine pancreatic enzymes, despite considerable improvements in steatorrhea and in vivo proteolytic activities. In marked contrast, malabsorption of cobalamin was significantly (P less than 0.05) reversed by oral administration of canine pancreatic juice. These results indicate that pancreatic secretions have an important role in the normal absorption of cobalamin in the dog, a role that does not appear to be attributable to pancreatic enzymes, but is consistent with the existence of a pancreatic intrinsic factor in this species.     

Pancreatic enzyme supplementation in normal and exocrine pancreatic insufficient pigs

The effect of pancreatic enzyme preparation (Combizyme Forte granulate) on the growth rate of normal, sham-operated and pancreatic duct ligated growing pigs was studied in 2 trials. In the first trial 6 normal Yorkshire pigs were fed a pancreatic enzyme supplement and 6 other pigs from the same litter were fed without supplementation. The growth rate over a period of 4 weeks was not significantly greater in the supplemented group. In a second trial exocrine pancreatic insufficiency, without diabetic symptoms, was produced in 12 pigs (aged 1.5 months and weighing 14 kgs) by ligation of the main pancreatic duct. The growth rates over a period of 20 days after surgery were 240 g, 454 g and 483 g/day in ligated pigs, in ligated pigs supplemented with pancreatic enzyme and in sham-operated control pigs, respectively. The difference between the ligated groups was significant (p less than 0.01) indicating the efficiency of the pancreatic enzyme therapy.     

Liver biochemical and histopathological findings in dogs with experimentally induced exocrine pancreatic insufficiency

Routine liver biochemical parameters were evaluated in 8 dogs with exocrine pancreatic insufficiency (EPI) induced by surgical ligation of the pancreatic duct and the pancreatic branch of the pancreaticoduodenal artery and confirmed with the trypsin-like immunoreactivity test. Eight additional dogs were used as healthy controls. Data collection began at the 4th week postoperatively and continued weekly to the 21st week. In the dogs with EPI, the serum activity of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were consistently elevated. The serum total and conjugated bilirubin concentrations remained within normal limits throughout the experimental period. Histopathological study revealed hepatic lipidosis in the dogs with EPI. Therefore, since this condition seems to be an additional consequence of EPI in dogs, laboratory evaluation of dogs with EPI must include assessment of liver function, to determine if additional or different therapeutic measures are indicated.     

Biochemical changes in the jejunal mucosa of dogs with exocrine pancreatic insufficiency following pancreatic duct ligation

The effects of exocrine pancreatic insufficiency on the small intestinal mucosa were examined in dogs following pancreatic duct ligation. There were no significant changes either in villus architecture or enterocyte height after duct ligation, but numbers of bacteria in duodenal juice increased then subsequently decreased following treatment with exogenous pancreatic enzymes. Pancreatic insufficiency resulted in a considerable increase in the proportion of microvillar membrane proteins of molecular mass over 200 kDa from 3.3 +/- 4 per cent (mean +/- SEM) to 13.6 +/- 7.2 per cent, and this decreased to 6.9 +/- 5.2 per cent following pancreatic enzyme supplementation. However, anticipated increases in activities of maltase and sucrase were not observed following duct ligation, and there was a reduction in lactase activity which was reversed by pancreatic supplementation. Activities of marker enzymes for the other subcellular organelles showed relatively minor or no changes throughout the study. These findings are consistent with a specific role for pancreatic enzymes in the post-translational processing of intestinal microvillar membrane proteins, and suggest that reduced degradation of brush border proteins in the absence of pancreatic secretions may be masked by quantitative and qualitative changes in the intestinal microflora.     

Observations on exocrine pancreatic insufficiency in a family of English setter dogs

The aim of this paper is to report serum trypsin-like immunoreactivity (TLI) concentrations in the progeny of a pair of English setters. These dogs had a history of producing puppies with a high prevalence of exocrine pancreatic insufficiency (EPI) secondary to either congenital deficiency or early onset juvenile atrophy of pancreatic acinar cells. Serum TLI concentrations in the clinically healthy parents of the puppies with EPI were normal, as were serum TLI concentrations in the unaffected puppies. However, serum TLI concentrations were extremely low (less than 1 μg/litre) in three puppies at eight to 12 weeks of age when clinical signs of EPI were present. In addition, one of the three puppies, with low TLI concentrations at eight weeks of age, had serum TLI concentrations of 0.7 μg/litre at two weeks of age even though no clinical signs were evident at that time. These results suggest that serum TLI assay may be a useful diagnostic aid in identifying puppies at a very early age with this unusual form of EPI.     

Effects of diet on clinical signs of exocrine pancreatic insufficiency in dogs

OBJECTIVE: To assess the effects of dietary modification on clinical signs of exocrine pancreatic insufficiency (EPI) in dogs. DESIGN: Blinded randomized crossover study. ANIMALS: 21 dogs with EPI. PROCEDURE: Dogs were fed the diet they received at home for 2 weeks. Thereafter, they received 3 special diets (a high-fat diet, a high-fiber diet, and a highly digestible low-residue diet) for 3 weeks each. Owners scored dogs daily for the last 2 weeks of each 3-week period for severity of 6 clinical signs including appetite, defecation frequency, consistency of feces, borborygmus, flatulence, and coprophagia. An EPI index was calculated for each dog by adding the daily scores for each clinical sign. RESULTS: Significant differences in daily EPI indices among diets were observed in 20 dogs. The original diet appeared to be the most suitable in 8 dogs, whereas the high-fat diet was most suitable in 5 dogs, the high-fiber diet was most suitable in 4 dogs, and the low-residue diet was most suitable in 2 dogs. In 1 dog, the lowest EPI index score was the same during the original diet and the high-fat diet feeding periods. One dog did not complete the feeding period for the high-fiber diet. Differences in mean EPI indices among diets were not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that responses to different diets varied among individual dogs. Because responses to the feeding regimens were unpredictable, it is suggested that feeding regimens be individually formulated for dogs with EPI.     

Mesenteric torsion in dogs with exocrine pancreatic insufficiency: 21 cases (1978-1987)

Mesenteric torsion was diagnosed in 21 of 199 German Shepherd Dogs suffering from exocrine pancreatic insufficiency. Eight dogs were euthanatized at the request of the owners; 4 dogs died at home before any treatment for mesenteric torsion was initiated. Surgery was performed on 9 dogs, all of which died during recovery from anesthesia.     

Multifocal necrotising steatites associated with pancreatic carcinoma in three dogs

Multiple subcutaneous swellings and discharging sinuses were a result of steatitis in three dogs. The steatitis in each case was thought to be associated with a pancreatic carcinoma. The association with pancreatic neoplasia had been suspected in life in only one dog but was confirmed at necropsy in each case. Circulating levels of pancreatic enzymes were increased in the one dog in which they were measured.     

An immunoassay for canine pancreatic elastase 1 as an indicator for exocrine pancreatic insufficiency in dogs.

The detection of pancreatic elastase 1 in stool samples has become the noninvasive gold standard for the diagnosis of pancreatic insufficiency in humans. Accordingly, the development of a sandwich-ELISA specific for canine pancreatic elastase 1, based on monoclonal antibodies, is presented here. The test has a detection range of 4-240 microg canine pancreatic elastase l/g feces. The intraassay coefficient of variation is 7.4%, and the interassay coefficient of variation is 7.7%. Spiking experiments show that canine elastase 1 is quantitatively detectable in fecal samples. Interestingly, the range of the elastase 1 concentration in canine feces within several days is higher as compared with humans. As the proposed cutoff of 10 microg/g is below this variation range in 96.1% of the tested samples, the effect on the test specificity is negligible. Because the test detects neither human nor bovine and porcine elastase 1, pancreatic function can be monitored without interrupting an enzyme replacement therapy.     

Serum feline trypsin-like immunoreactivity in cats with exocrine pancreatic insufficiency

Exocrine pancreatic insufficiency is thought to occur rarely in cats. This assumption has been made based on the lack of a specific test for this disease in the cat. Clinical data from the 1st 20 cats with serum feline trypsin-like immunoreactivity (fTLI) concentrations < or = 8 microg/L are presented. In 17 of these 20 cats compelling evidence for a diagnosis of exocrine pancreatic insufficiency (EPI) was present and in the remaining 3 supportive evidence for a diagnosis of EPI was available. The conclusion was made that serum fTLI concentration is a specific test for EPI in the cat.     

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.     

Breed associations for canine exocrine pancreatic insufficiency

BACKGROUND: Knowledge of breed associations is valuable to clinicians and researchers investigating diseases with a genetic basis. HYPOTHESIS: Among symptomatic dogs tested for exocrine pancreatic insufficiency (EPI) by canine trypsin-like immunoreactivity (cTLI) assay, EPI is common in certain breeds and rare in others. Some breeds may be overrepresented or underrepresented in the population of dogs with EPI. Pathogenesis of EPI may be different among breeds. ANIMALS: Client-owned dogs with clinical signs, tested for EPI by radioimmunoassay of serum cTLI, were used. METHODS: In this retrospective study, results of 13,069 cTLI assays were reviewed. RESULTS: An association with EPI was found in Chows, Cavalier King Charles Spaniels (CKCS), Rough-Coated Collies (RCC), and German Shepherd Dogs (GSD) (all P < .001). Chows (median, 16 months) were younger at diagnosis than CKCS (median, 72 months, P < .001), but not significantly different from GSD (median, 36 months, P = .10) or RCC (median, 36 months, P = .16). GSD (P < .001) and RCC (P = .015) were younger at diagnosis than CKCS. Boxers (P < .001), Golden Retrievers (P < .001), Labrador Retrievers (P < .001), Rottweilers (P = .022), and Weimaraners (P = .002) were underrepresented in the population with EPI. CONCLUSIONS AND CLINICAL IMPLICATIONS: An association with EPI in Chows has not previously been reported. In breeds with early-onset EPI, immune-mediated mechanisms are possible or the disease may be congenital. When EPI manifests later, as in CKCS, pathogenesis is likely different (eg, secondary to chronic pancreatitis). Underrepresentation of certain breeds among dogs with EPI has not previously been recognized and may imply the existence of breed-specific mechanisms that protect pancreatic tissue from injury.