Gastrinoma

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Also known as: Zollinger-Ellison Syndrome

Introduction

A gastrinoma is a neoplasm of pancreatic islet cells that secretes the hormone gastrin, an example of an ectopic paraneoplastic disease. The disease was first described by Zollinger and Ellison in humans in 1955 and it has since been recognised occasionally in dogs and cats. Gastrinomas are the least common of the islet cell neoplasia, the other types being glucagonomas and insulinomas.

The excessive secretion of gastrin leads to hyperplasia of the crypt cells of the antral gastric mucosa and hyperstimulation of gastric acid production from the parietal cells of the stomach. Antral hyperplasia may result in gastric outflow obstruction. The excessive secretion of gastric acid leads to gastro-duodenal ulceration and oesophagitis due to gastro-oesophageal reflux. In severe cases of the disease, deep gastric ulcers may erode blood vessels causing haemorrhage or perforate, causing septic peritonitis. Gastrinomas have often metastasised to local lymph nodes or to the liver at the time of diagnosis.

Signalment

Gastrinomas have only ever been reported in a very few dogs and cats and the disease is extremely rare.

Diagnosis

Clinical signs

Affected animals may show few clinical signs as the condition first develops but, in more advanced cases, the following signs may be documented:

  • Anorexia and severe weight loss
  • Vomiting which may contain blood if blood vessels are eroded (haematemesis). Vomiting occurs due to gastric irritation and possible gastric outflow obstruction.
  • Diarrhoea which may show evidence of haemorrhage in the upper gastro-intestinal tract (melaena). Diarrhoea occurs due to the production of excessive volumes of gastric secretions and because gastrin reduces the ability of the intestine to absorb fluid and electrolytes. Malabsorption may occur due to small intestinal villous atrophy.
  • Collapse and shock if an ulcer perforates to cause peritonitis.
  • Severe haemorrhage may result in pallor, tachycardia, a haemic murmur and collapse

Affected animals may also show signs of oesophagitis, including regurgitation and hypersalivation.

Laboratory Tests

Haematology

If haemorrhage is occurring, the packed cell volume (PCV) and blood haemoglobin concentration may be abnormally low and there may be signs of regeneration after 48-72 hours. In cases of chronic haemorrhage, the blood urea concentration may be raised and, as iron reserves are expended, a microcytic hypochromic anaemia may develop.

Areas of gastro-duodenal ulceration will be inflamed, producing a leuccoytosis. This may be neutrophilic, monocytic or both depending on the stage of disease.

Biochemistry

Blood urea concentration may be elevated in cases of gastro-intestinal haemorrhage. Haemorrhage will lead to the loss of plasma proteins, producing a hypoalbuminaemia.

Repeated bouts of gastric vomiting may lead to the loss of gastric acid and intestinal fluid, producing hyponatraemia, hypokalaemia, hypochloraemia and metabolic alkalosis.

Diagnostic Imaging

Ultrasonography is most useful for detection of gastro-duodenal ulceration and of metastases in the liver, peritoneal cavity and local lymph nodes[1].

Ulceration and antral hyperplasia may also be visualised by endoscopy.

Other Tests

It is possible to measure the gastric pH using a pH meter placed into the stomach. The pH in affected animals will be persistently lower than that of normal animals.

In humans, Zollinger-Ellison syndrome is diagnosed by directly measuring serum gastrin concentration before or after injecting secretin or calcium, which both stimulate secretion. These tests have all been performed in animals but, given the very low prevalence of the disease, they are not widely available. Serum gastrin concentration may be elevated in many other disease conditions and a single basal measurement is not sufficiently specific to make a diagnosis of gastrinoma in dogs[2][3].

Pathology

Post mortem examination of the pancreas of affected animals may reveal multiple variably sized neoplasms that feel firm because they have a large connective tissue mass. The tumours may be partially encapsulated and locally invasive. Metastases are commonly detected in the liver or local lymph nodes.

Treatment

Ideally, the tumour should be excised surgically by performing a partial pancreatectomy. Intra-operative ultrasound scans can be performed if the mass is not evident within the pancreatic parenchyma. Any evident metastatic masses can also be biopsied or resected during the procedure. Gastric hyperacidity usually recurs soon after resection, probably due to the presence of extra-pancreatic metastases.

The somatostatin analogue octreotide has been used pre- and post-opratively in the management of gastrinomas [4]but so few cases have been described that it is not clear if this therapy is beneficial. Adjunctive therapy with gastro-protectants such as sucralfate and with inhibitors of gastric acid secretion (such as omeprazole, ranitidine or cimetidine) is also indicated to reduce the severity of gastro-duodenal ulceration and the signs it causes.

Prognosis

In approximately 85% of cases, gastrinomas have metastasised at the time of diagnosis and the tumour is likely to recur after surgical resection.


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References

  1. Robben JH, Pollak YW, Kirpensteijn J, Boroffka SA, van den Ingh TS, Teske E, Voorhout G. Comparison of ultrasonography, computed tomography, and single-photon emission computed tomography for the detection and localization of canine insulinoma. J Vet Intern Med. 2005 Jan-Feb;19(1):15-22.
  2. Gabbert NH, Nachreiner RF, Holmes-Wood P, Kivela JH. Serum immunoreactive gastrin concentrations in the dog: basal and postprandial values measured by radioimmunoassay Am J Vet Res. 1984 Nov;45(11):2351-3.
  3. Happé RP, van der Gaag I, Lamers CB, van Toorenburg J, Rehfeld JF, Larsson LI. Zollinger-Ellison syndrome in three dogs. Vet Pathol. 1980 Mar;17(2):177-86.
  4. Altschul M, Simpson KW, Dykes NL, Mauldin EA, Reubi JC, Cummings JF. Evaluation of somatostatin analogues for the detection and treatment of gastrinoma in a dog. J Small Anim Pract. 1997 Jul;38(7):286-91.

Image of pancreatic gastrinoma in a dog from Cornell Veterinary Medicine

Ettinger, S.J, Feldman, E.C. (2005) Textbook of Veterinary Internal Medicine (6th edition, volume 2) W.B. Saunders Company




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