+ General Considerations
- Gastrinomas are non-β-islet cell pancreatic tumors
- Zollinger-Ellison syndrome is the triad of gastric acid hypersecretion, peptic ulceration, and gastrinoma
- Gastric acid hyperacidity causes erosive gastritis and duodenitis, gastric mucosal hyperplasia, and ulceration
+ Biologic Behavior
- Gastrinoma is primarily a pancreatic tumor, however, extrapancreatic gastrinoma has been reported in the root of the mesentery in 1 dog
- Gastrinomas are usually solitary with 60% in the right lobe, 40% pancreatic body, and left lobe rarely involved
- Metastasis is common with 76%-85% at presentation: liver (65%), regional lymph nodes (30%), and 25% to spleen, peritoneum, and mesentery
- Gastrointestinal ulceration is common and occurs in 95% of cats and dogs with gastrinomas
- Esophageal ulceration in 20%
- Gastric ulceration in 45%
- Duodenal ulceration in 78%
- Jejunal ulceration in 6%
- GI perforation in 25%
+ Clinical Signs
- Vomiting and weight loss are the most common clinical signs
- Other clinical signs include depression, lethargy, anorexia, and intermittent diarrhea
- Polydipsia, melena, abdominal pain, hematemesis, hematochezia, and obstipation are uncommon
- GI ulceration can cause hematemesis, melena, hematochezia, and abdominal pain
- Gastroesophageal reflux and esophagitis can cause anorexia, regurgitation, hematemesis, and weight loss
- Duodenal acidification inactivates lipase and bile salts through direct chemical injury to the duodenal mucosa and through gastrin inhibition of water and electrolyte absorption and causes malabsorption and steatorrhoea
- Common findings include regenerative anemia (45%) and leukocytosis with neutrophilia and left shift (10%-50%)
- Regenerative anemia due to GI hemorrhage
- Leukogram changes due to GI inflammation
- Common abnormalities include increased ALP, hyperglycemia, hypoalbuminemia, hypokalemia, and hypocalcemia
- Other abnormalities include mild hyponatremia, hypochloremia, hypoproteinemia, hypoglycemia, acidosis or alkalosis, and increased bilirubin, creatinine, and ALT
- Hypoalbuminemia and hypoproteinemia due to loss of proteins through gastric erosions and ulceration
- Hypocalcemia is associated with protein loss, but steatorrhea and vitamin D malabsorption may also be involved
- Hypokalemia due to decreased oral intake and potassium ion loss through vomiting and diarrhea
- Vomiting results in hyponatremia, hypochloremia, and metabolic acidosis
- Elevated liver enzymes most frequent due to metastatic disease in the liver
- Serum gastrin levels can be measured with radioimmunoassay
- Normal serum gastrin levels are 28-135 pg/ml in cats and 12-190 pg/ml in dogs
- Basal gastrin concentration is increased by > 3.2 times the normal upper limit of reference range
- However, hypergastrinemia is not pathognomonic for gastrinoma as gastrin can be increased in chronic renal failure, gastric outlet obstruction, GDV, chronic and atrophic gastritis, Basenji immunoproliferative enteropathy, liver disease, following small intestinal resection, and with H 2-receptor antagonist therapy
- Gastrin levels are usually lower with this conditions than commonly seen associated with gastrinoma
- Provocative tests are indicated for animals with normal to mildly elevated gastrin levels
- Provocative tests include secretin or calcium stimulation
- Secretin and calcium increase gastrin production with gastrinoma due to lack of negative feedback control
- Secretin stimulation test is preferred and increases gastrin levels by > 2 times if gastrinoma
- Combined secretin-calcium stimulation test is used in humans
- Perforation or peritonitis occurs in up to 25% animals with loss of serosal detail or pneumoperitoneum
- Positive- or double-contrast radiographs with GI ulcers appearing as outpocketing from the GI lumen
- Positioning important and fluoroscopy may improve detection
- Abnormal findings include plaque-like defects in the fundic and duodenal mucosa, prominent rugal folds, thickened pyloric antrum, complete pyloric obstruction, intestinal thickening, and delayed gastric emptying
- Human criteria for differentiation of benign and malignant ulceration includes ulcer penetration, mucosal pattern adjacent to ulcer, tissue undermining, and shape of tissue surrounding ulcer
- Gastric ulcers can be difficult to detect because of shallow ulcers; ulcers filled with residues of mucous, blood, food, or necrotic tissue; edematous margins prevent entry of barium; and rugal folds may obscure ulcer
- Ultrasonographic findings of gastric ulceration include local mural thickening, loss of the 5-layer structure, presence of a defect in the gastric wall, fluid accumulation in the lumen of the stomach, and diminished gastric motility
- Endoscopy is the preferred for diagnosing GI ulceration as the mucosal surface can be directly visualized ± biopsied
- Abnormal findings include esophagitis and esophageal ulceration, thickened gastric rugae, gastric ulceration and hemorrhage, excessive liquid in stomach, hypertrophy of pyloric antrum, and duodenal ulceration
- Scintigraphy has 2 roles:
- Localizes GI bleeding through labeling erythrocytes with 99m technetium
- Somatostatin receptor scintigraphy can localise primary and metastatic gastrinomas and provide an indication of those tumors likely to respond to anti-somatostatin therapy
- Aims of surgical management of gastrinoma include:
- Surgical removal of the primary tumor and clinical staging
- Control of gastric acid hypersecretion
- Treatment of GI ulceration ± perforation and intra-abdominal sepsis
- Correction of fluid, electrolyte, and acid-base disturbances
- Approach: ventral midline celiotomy
- Abdominal exploration with thorough examination of pancreas for primary tumor and inspection of liver, lymph nodes, GI, spleen, omentum, and mesentery for ulceration and metastatic disease
- Partial pancreatectomy or enucleation should be performed if the tumor can be identified
- Debulking acceptable if large as gastrinoma are slow growing and debulking reduces gastrin secretory capacity
- Intraoperative ultrasound can be used if tumor cannot be found
- Partial pancreatectomy of right limb if tumor not found due to high percentage of right limb involvement
- Proton pump inhibitors (i.e., omeprazole) preferred as more profound suppression of gastric acid secretion than H 2-receptor antagonists and inhibits gastric acid secretion regardless of the secretagogue, and only requires once daily administration
- Omeprazole is associated with prolonged survival times in cats and dogs with incompletely resected and metastatic gastrinoma
- chronic suppression of gastric acid secretion stimulates production of gastrin by G cells in the pyloric antrum and results in hyperplasia of enterochromaffin-like cells and gastric carcinoid tumors in rats
- H 2 receptor antagonists (i.e., cimetidine, ranitidine, or famotidine)
- somatostatin analogues (i.e., octreotide) inhibits both gastrin and hydrochloric acid secretion and has been used successfully in dogs with gastrinoma
- sucralfate binds to ulcerated areas and increase re-epithelialization, mucus production, prostaglandin synthesis, and neutralizes bile acids
- misoprostol is recommended for prevention and treatment of NSAID-induced gastroduodenal ulcers
- chemotherapy has not been reported in animals
- doxorubicin, 5-fluoroucil, and streptozotocin have been used as sole agents or in combination in humans
- prognosis is guarded due to high metastatic rate
- however, prolonged survival (> 10 months) can be achieved with surgical resection and antacid therapy
Clinicopathological Abnormalities in 14 Dogs with Gastrinoma
| CLINICOPATHOLOGICAL FINDING | NUMBER OF DOGS | PERCENTAGE OF DOGS |
| Hypoproteinemia hypoalbuminemia | 8 | 57 |
| Hypokalemia | 6 | 43 |
| Anemia | 6 | 43 |
| Increased alkaline phosphatase | 6 | 43 |
| Hypochloremia | 5 | 36 |
| Leukocytosis | 5 | 36 |
| Hyperglycemia | 3 | 21 |
| Increased alanine aminotransferase | 3 | 21 |
| Hypoglycemia | 1 | 7 |
| Hyponatremia | 1 | 7 |
| Hyperbilirubinemia | 1 | 7 |
| Increased blood urea nitrogen | 1 | 7 |
| Hypocalcemia | 1 | 7 |
Basal Gastrin Concentration
Provocative Tests
Survey Radiographs
Contrast Radiographs and Fluoroscopy
Ultrasonography
Endoscopy
Nuclear Scintigraphy
TREATMENT
Surgical Management
Postoperative Management
Gastric Hyperacidity
Gastric Ulceration
Chemotherapy
Prognosis
PANCREATIC GASTRINOMA
Incidence of Clinical Signs of Gastrinoma in 23 dogs and 2 Cats
| CLINICAL SIGN | NUMBER OF ANIMALS | PERCENTAGE OF ANIMALS |
| Vomiting | 23 | 92 |
| Weight loss | 22 | 88 |
| Anorexia | 18 | 72 |
| Lethargy, depression | 16 | 64 |
| Diarrhea | 15 | 60 |
| Polydipsia | 6 | 24 |
| Melena | 6 | 24 |
| Abdominal Pain | 6 | 24 |
| Hematemesis | 3 | 12 |
| Hematochezia | 3 | 12 |
| Fever | 2 | 8 |
| Ravenous Appetite | 2 | 8 |
| Abdominal Mass | 1 | 4 |
| Tachycardia | 1 | 4 |
| Obstipation (alternating with diarrhea) | 1 | 4 |
From: Withrow SJ & MacEwen EG (eds): Small Animal Clinical Oncology (3rd ed).