Gastrinoma and Zollinger-Ellison syndrome in canids: a literature review and a case in a Mexican gray wolf.

Gastrinoma, an infrequent diagnosis in middle-aged dogs, occurs with nonspecific gastrointestinal morbidity. Laboratory tests can yield a presumptive diagnosis, but definitive diagnosis depends on histopathology and immunohistochemistry. We describe a malignant pancreatic gastrinoma with lymph node metastases and corresponding Zollinger-Ellison syndrome in a Mexican gray wolf ( Canis lupus baileyi) and review this endocrine neoplasm in domestic dogs. A 12-y-old, captive, male Mexican gray wolf developed inappetence and weight loss. Abdominal ultrasonography revealed a thickened duodenum and peritoneal effusion. Two duodenal perforations were noted on exploratory celiotomy and were repaired. Persisting clinical signs led to a second celiotomy that revealed a mesenteric mass, which was diagnosed histologically as a neuroendocrine carcinoma. During the following 16 mo, the wolf received a combination of H2-receptor antagonists, proton-pump inhibitors, gastroprotectants, and anti-emetics, but had recurrent episodes of anorexia, nausea, acid reflux, and remained underweight. Worsening clinical signs and weakness prompted euthanasia. The antemortem serum gastrin concentration of 414 ng/L (reference interval: 10-40 ng/L) corroborated hypergastrinemia. Autopsy revealed a mass expanding the right pancreatic limb; 3 parapancreatic mesenteric masses; duodenal ulcers; focal duodenal perforation with septic fibrinosuppurative peritonitis; chronic-active ulcerative esophagitis; and poor body condition. The pancreatic mass was diagnosed histologically as a neuroendocrine carcinoma and the parapancreatic masses as lymph node metastases. Immunohistochemistry of the pancreatic mass was positive for gastrin and negative for glucagon, insulin, pancreatic polypeptide, serotonin, somatostatin, and vasoactive intestinal peptide.

Omeprazole in a dog with gastrinoma.

A 9-year-old male German Shepherd Dog was presented with the primary complaints of vomiting, profuse watery diarrhea, anorexia, and severe weight loss. The dog developed hematemesis and melena, which were unresponsive to treatment with an H2-receptor antagonist and a gastrointestinal protectant. A marked neutrophilia, panhypoproteinemia, hypokalemia, and mildly increased activities of alkaline phosphatase and alanine aminotransferase were the only relevant abnormalities found on a CBC, serum biochemical profile, and urinalysis. An exploratory laparotomy revealed several small nonresectable masses at the root of the mesentery, which were identified histologically as a neuroendocrine neoplasm. Immunohistochemical staining of the neoplasm was positive for gastrin and negative for insulin, glucagon, pancreatic polypeptide, and vasoactive intestinal polypeptide. Fasting serum gastrin concentrations were high. Zollinger-Ellison syndrome was diagnosed, and the dog was treated with omeprazole, an H+,K(+)-ATPase inhibitor. All clinical signs resolved, and the dog remains asymptomatic 2 years later. Omeprazole may be the gastric acid antisecretory drug of choice for dogs with gastrinoma.

The Brooklyn gastrinomas.

During the past seven years we have diagnosed and treated 12 patients with the Zollinger-Ellison syndrome (ZES), some of whom have had virtually unique manifestations. Among these are a 74-year-old man who was cured after endoscopic removal of a submucosal duodenal gastrinoma, suggesting the usefulness of an operative approach using intraoperative endoscopic transillumination; a 33-year-old man in whom the manifestations of ZES brought him into conflict with the law; and a 10-year-old domestic cat who was cured surgically, the gastrinoma providing material for the first determination of the sequence of cat gastrins.

Clinical management of tumours in geriatric dogs and cats: systemic effects of tumours and paraneoplastic syndromes.

There are many clinical presentations of neoplastic disease in the dog and cat. Some relate to the presence of a solid mass but many relate to the systemic effect that the tumour has on the animal. This paper covers the broad categories of the systemic metabolic and haematological effects that are associated with tumours in the dog and cat.

Zollinger-Ellison syndrome in a cat.

Zollinger-Ellison Syndrome in a 12-year old castrated male European Shorthair cat is described. The clinical symptoms were vomiting, weight loss, listlessness and alternating diarrhoea and obstipation. An endocrine tumour near the pancreatic duct had metastasised to the liver. Many duodenal ulcers were present. Immunohistochemistry revealed cells positive for gastrin and neuron-specific enolase (NSE) scattered throughout the tumour.

Zollinger-Ellison syndrome and myelofibrosis in a dog.

Zollinger-Ellison syndrome and myelofibrosis were diagnosed concurrently in a 10-year-old neutered female Brittany Spaniel. Documentation of gastric ulceration, hypergastrinemia, and gastrin-secreting islet cell tumor with splenic metastases facilitated the diagnosis of Zollinger-Ellison syndrome. Patchy long-bone medullary sclerosis, nonregenerative anemia and thrombocytopenia, multiple acellular bone marrow aspirates, marked splenic extramedullary hematopoiesis, and acellular core bone marrow biopsy with areas of necrosis and fibrosis supported the diagnosis of myelofibrosis. Despite the medical and surgical management attempted, the dog was euthanatized because of signs of severe intractable bone pain. Myelofibrosis has been documented in association with canine and human neoplastic disease. A direct causal relationship between gastrinoma and myelofibrosis was not clearly established in this instance.

Serum immunoreactive gastrin concentrations in the dog: basal and postprandial values measured by radioimmunoassay.

A commercially available radioimmunoassay designed for quantitating human gastrin was evaluated for use in quantitating dog gastrin. Because of the similarities in molecular structures of the two, the assay appears to be useful for dogs. Serum gastrin concentration in 12 fasting dogs averaged 64.8 pg/ml. After dogs were fed, the concentration increased to 117.8 pg/ml within 30 minutes and returned to base line by 90 minutes. A standard feeding procedure may be useful in evaluating dogs with gastrinoma.

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.

Canine Zollinger-Ellison syndrome.

The unusual finding of peptic esophagitis and duodenal ulceration in a dog was associated with a malignant pancreatic islet cell tumor producing gastrin and ACTH. The finding of a gastrinoma in a non-human species introduces the potential for developing an animal model for the study of the protean genetic biochemical, physiologic and metabolic aspects of the Zollinger-Ellison syndrome.