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Pancreas: neoplasia: gastrinoma
(Zollinger-Ellison syndrome) 		Feedback

Introduction
  • Rare. No predilection to age or breed evident.
  • Cause : functional malignant tumor of pancreatic islet cells that secretes gastrin.
  • Signs : attributable to gastrin produced by tumor (hypergastrinemia) causing esophageal, gastric and duodenal ulceration leading to vomiting and diarrhea.
  • Diagnosis : laparotomy and histopathology.
  • Treatment : surgical excision + H2 blockers.
  • Prognosis : poor >76% metastasize.

Presenting signs
  • Maldigestion:
    • Vomiting Vomiting.
    • Weight loss Weight loss: overview.
    • Anorexia.
  • Malabsorption:
    • Excessive secretion of gastric acid results in mucosal ulcerations Gastric ulceration and maldigestion leading to diarrhea Diarrhea: due to systemic illness.
    • Lethargy.
    • Pain Pain.
    • Pyrexia.
  • Hematemesis.
  • Melena.


Age predisposition
  • Mean age 7.5 years.

Sex predisposition
  • Females.

Cost considerations
  • Moderate cost if surgery is required.
  • Relatively expensive drugs required for treatment of gastrointestinal ulceration and acid control.
Pathogenesis Top

Etiology
  • Unknown.

Pathophysiology
  • Malignant tumor of islet cells secreting gastrin.
  • Gastrin stimulates excessive gastric hydrochloric acid secretion causing gastrointestinal ulceration, diarrhea and steatorrhea.
  • Gastrin right_arrow gastric hydrochloric acid right_arrow erosive gastritis/duodenitis right_arrow ulceration/hyperplasia right_arrow vomiting/hematemesis/melena/abdominal pain.
  • Excessive gastrointestinal acid right_arrow fat malabsorption right_arrow steatorrhea/diarrhea.
  • High malignancy right_arrow metastasis to liver and regional lymph nodes.

Timecourse (incubation, duration)
  • Early metastasis.

Diagnosis Top

Presenting problems
  • Vomiting.
  • Weight loss.
  • Anorexia.

Client history
  • Non specific signs of illness depending on stage of disease and complications:
    • Vomiting Vomiting.
    • Anorexia.
    • Weight loss Weight loss: overview.
    • Cachexia.
    • Depression.
    • Pyrexia.
    • Diarrhea Diarrhea: due to systemic illness.
    • Anemia Anemia: overview.
  • Hematemesis.
  • Melena.
  • Polydipsia.

Clinical signs
  • Abdominal pain.

Diagnostic investigation

Laparotomy Laparotomy: midline 
  • Pancreatic tumor identified.
Histopathology
  • Non-beta cell islet cell tumor.
  • Gastric mucosal hypertrophy.
  • Cellular infiltrates.

Contrast Radiography
  • Barium contrast studies to demonstrate gastric, duodenal or esophageal ulceration.
  • Thickened gastric lining.
2-D Ultrasonography
  • In some cases may see gastric/duodenal ulceration.
  • Thickened gastric lining.
  • Variable utility as gastrinomas may be microscopic.

    Endoscopy

  • Gastroscopy Gastroscopy shows gastric/duodenal ulceration.
  • Gastric mucosal hypertrophy.
  • Inflammatory lesions with thickened rigid gastric rugae.

Other
  • High acidity.
  • High serum gastrin levels - supportive.
  • Fecal analysis for occult blood Fecal analysis: occult blood may be positive.

    Hematology

  • Regenerative anemia Hematology: packed cell volume if bleeding from ulceration is significant.
  • Leukocytosis with left shift.
Biochemistry
    • Electrolyte imbalances associated with chronic vomiting:
      • Hyperglycemia Blood biochemistry: glucose.
      • Hypoalbuminemia Blood biochemistry: albumin.
      • Hypocalcemia Blood biochemistry: total calcium.
      • Hypochloremia Blood biochemistry: chloride.
      • Hypokalemia Blood biochemistry: potassium.
      • Hypoproteinemia Hypoproteinemia.

Confirmation of diagnosis
Discriminatory diagnostic features
  • Endoscopy.
  • Contrast radiography.
  • Measurement of serum gastrin levels if practical.
  • Lack of response to standard treatments for gastroduodenal ulceration.

Definitive diagnostic features
  • Laparoscopy (presence of pancreatic mass).
  • Histopathology (identification of excised specimen).

Gross autopsy findings
  • Pancreatic tumor.
  • Gastric/duodenal ulceration.
  • Gastrointestinal wall hyperplasia.

Histopathology findings
  • Pancreatic, non-beta cell islet cell tumor.

Differential diagnosis
  • Foreign body Stomach: foreign body.
  • Intussusception Intussusception.
  • Renal failure Kidney: acute renal failure  Chronic renal failure.
  • Hepatic disease Liver: acute disease  Liver: chronic disease.
  • Inflammatory bowel disease Inflammatory bowel disease: overview.
  • Gastrointestinal lymphosarcoma Lymphoma.

Treatment Top
Initial symptomatic treatment
  • Fluid therapy Fluid therapy where excessive fluid loss, eg vomiting, diarrhea.

Standard treatment
  • Surgical excision of tumor (if solitary lesion).
  • Surgical resection of large peptic ulcers.
  • Suppression of gastric acid secretion:
    • Using H2 blockers, eg cimetidine Cimetidine (5-10 mg/kg PO TID) or ranitidine Ranitidine (2 mg/kg PO BID).
    • Using proton pump inhibitors, eg omeprazole Omeprazole.
    • Using prostaglandin analogues eg misoprostol Misoprostol.
  • Treatment of gastric ulcers, eg sucralfate Sucralfate (1 g TID (large dogs); 0.5 g TID (small dogs).

Monitoring
  • Following pancreatic surgery, acute pancreatitis Pancreatitis: acute may occur.

Subsequent management

Monitoring
  • 2-3-weekly hematology/biochemistry examinations.
  • Examine regional lymph nodes for metastasis on a regular basis.

Sequelae Top
Prognosis
  • Poor: highly malignant.
  • Metastatic spread causes 76% cases to recur even after apparently successful surgery.
  • Mean survival time of 5 months.

Expected response to treatment
  • Stabilize condition on medical therapy.
  • Cessation of vomiting.

Reasons for treatment failure
  • Tumor metastasized at time of diagnosis.

Sources Top
Publications
Refereed papers
  • Recent references from PubMed.
  • Green R A & Gartrell C L (1997) Gastrinoma - a retrospective study of four cases (1985-1995). JAAHA 33 , 524-527.
  • Zerbe C A & Washabau R J (1995) Gastrointestinal endocrine disease. In: Textbook of Veterinary Internal Medicine. 4th edn. Eds S J Ettinger and E C Feldman. Philadelphia: Saunders.
  • Happe et al(1980) Zollinger-Ellison syndrome in three dogs. Vet Pathol 17 , 177-186.

Vetstream contributor(s)
  • Dr James W Simpson SDA BVM&S MPhil MRCVS , RCVS Specialist Internal Medicine, Department of Veterinary Clinical Studies, Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK.
  • Andrew Gardiner DVM&S CertSAS MRCVS, 8/6 Hermit's Croft, St Leonards, Edinburgh EH8 9RF, UK.
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Anemia: overview
Blood biochemistry: albumin
Blood biochemistry: chloride
Blood biochemistry: glucose
Blood biochemistry: potassium
Blood biochemistry: total calcium
Chronic hypertrophic gastritis
Chronic renal failure
Cimetidine
Diarrhea: due to systemic illness
Fecal analysis: occult blood
Fluid therapy
Gastric ulceration
Gastroscopy
Hematology: packed cell volume
Hypoproteinemia
Inflammatory bowel disease: overview
Intussusception
Kidney: acute renal failure
Laparotomy: midline
Liver: acute disease
Liver: chronic disease
Lymphoma
Misoprostol
Octreotide
Omeprazole
Pain
Pancreas: neoplasia
Pancreatitis: acute
Ranitidine
Stomach: foreign body
Sucralfate
Vomiting
Weight loss: overview
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