Gastrinoma

Gastrinoma Background A gastrinoma is a gastrin-secreting tumor that can occur in the pancreas, although it is most commonly found in the duodenum. Duodenal wall gastrinomas have been identified in 4050% of patients.

These duodenal wall tumors are frequently small and multiple.

Gastrinoma

• Background • Sporadic tumors occurring in the pancreas tend to be solitary and have greater malignant potential as compared to duodenal gastrinomas.

Gastrinoma • Background • More than 80% of gastrinomas arise within the triangle defined as the confluence of the cystic and common bile duct superiorly, the second and third portions of the duodenum inferiorly, and the neck and body of the pancreas medially.

Gastrinoma • Background • Rarely, primary tumors also occur in a variety of ectopic sites, including: • the body of the stomach • jejunum • peripancreatic lymph nodes • splenic hilum • omentum, liver, gallbladder, common bile duct. • and the ovary.

• Background • Over 50% of gastrinomas are malignant and can metastasize to regional lymph nodes and the liver. • One fourth of gastrinomas are related to multiple endocrine neoplasia (MEN) type I and are associated with hyperparathyroidism and pituitary adenomas.

• Background • The triad: • of non-beta islet cell tumors of the pancreas (gastrinomas) • hypergastrinemia • and severe ulcer disease • Was described by Zollinger and Ellison in 1955, hence the eponym Zollinger-Ellison syndrome (ZES).

• Background • International • The true incidence of ZES is not known. • ZES constitutes 0.1% or more of cases of peptic ulcer disease.

• Background • Mortality/Morbidity • The primary determinants of survival for patients with gastrinomas are the size of the primary tumor and the occurrence of tumor metastasis. • In patients with liver metastasis, the 5-year survival rate is 20-30% • In patients with localized disease or metastasis to local lymph nodes without liver metastasis, the 5-year survival rate is 90%.

• Background • Sex • Gastrinomas are more common in males than in females, with ratios from 1.5:1 to 2:1. • Age • Although gastrinomas can occur at any age, the initial clinical manifestation usually appears in people aged 30-50 years.

Gastrinomas

• Pathophysiology • Enormous secretion of gastrin from the tumor cells leads ►to hyperplasia of fundic parietal cells and ► increased basal acid secretion.

Gastrinomas • Pathophysiology • ► 1) This results in severe peptic ulcer disease. Ulceration might even extend into the small intestine.

• ► 2) The acidic content of the small intestine causes the release of secretin, which is responsible for the diarrhea, in part, caused by the outpouring of water and bicarbonate from the pancreas and small intestine.

Gastrinomas • Clinical Presentation

• History • The symptoms in 90-95% of patients with gastrinomas are similar to the symptoms of common peptic ulcer disease.

• Usually, persistent abdominal pain exists that is less responsive to medical treatment.

Gastrinomas • Clinical Presentation

• History • Sometimes, symptoms may relate to a complication of peptic ulcer disease, such as: • bleeding (e.g. melena, hematemesis) • gastric outlet obstruction (e.g. vomiting).

• and perforation (e.g. peritoneal irritation).

• Clinical Presentation

• History • Other symptoms include: • gastroesophageal reflux (GER) • diarrhea • steatorrhea • and weight loss. • ► All of which are secondary to acid hypersecretion. • Vitamin B-12 malabsorption.

Gastrinomas • Clinical Presentation

• History • Chronic acid reflux may lead to: • esophageal complications • e.g. esophagitis, • stricture formation • Barrett’s esophagus • ►in up to two thirds of patients with Zollinger-Ellison syndrome

Gastrinomas • Clinical Presentation • Clinical Examination • Epigastric tenderness is the most frequent abnormal physical finding. • Depending on the possible ulcer complications, signs may vary.

Gastrinomas • Clinical Presentation • Clinical Examination • Nearly 75% of ulcers in patients with gastrinomas are present in the first portion of the duodenum. • These ulcers usually are single or multiple and are indistinguishable from peptic ulcer disease.

Gastrinomas • Clinical Presentation • Clinical Examination • Nearly 10% of patients with ZES have no demonstrable ulcer. • Ulcers located in the second, third, or fourth portion of the duodenum or jejunum should increase the possibility of gastrinoma.

Gastrinomas • Clinical Presentation • Clinical Examination • The other factors that alert one to the presence of underlying gastrinomas are the following: • Ulcers that are refractory to standard therapy • • Multiple ulcers • Giant ulcers, larger than 2 cm • Recurrent ulcers

Gastrinomas • Clinical Presentation • Clinical Examination • Ulcers with unexplained diarrhea • Strong family history of ulcers • Hypercalcemia • Duodenal ulcer that is not related to Helicobacter pylori infection or nonsteroidal antiinflammatory drug use

Gastrinomas • Differential Diagnosis • Achlorhydria • Gastric Outlet Obstruction Gastritis, Atrophic • Peptic Ulcer Disease • Pernicious Anemia

Gastrinomas

• Lab Studies • The diagnosis is based on the following 3 criteria:

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Gastrinomas • Lab Studies • 1) Fasting hypergastrinemia is present: • >150 pg/mL with levels >100,000 pg/mL in some patients • 2) Basal acid output (BAO) is greater than 10 mEq/h. • 3) Results from a secretin stimulation test are positive.

Gastrinomas

• Imaging Studies • Imaging studies are helpful to help localize the tumor. • They also are helpful for assessing surgical resectability by helping reveal liver metastasis.

Gastrinomas

• Imaging Studies • Somatostatin receptor scintigraphy (SRS) is very useful for helping identify the primary lesions and metastasis.

Gastrinomas • Imaging Studies • Endoscopic ultrasound also has been found to be useful in helping detect primary tumor, with a reported overall sensitivity and accuracy of higher than 90% for intrapancreatic gastrinomas. • For extrapancreatic gastrinomas in the duodenal wall, endoscopic ultrasound is useful but somewhat less sensitive.

Gastrinomas

• Imaging Studies • CT scan and selective angiogram. • Also are helpful for detecting gastrinoma.

Gastrinomas

• Imaging Studies • Because of the large proportion of primary gastrinomas in the proximal duodenum, upper endoscopy may also be a useful tool in the localization of tumors in these patients.

Gastrinomas

• Treatment • Medical Care • Individualize the selection of treatment. Base treatment (antisecretory medications) on factors related to ulcer disease and diarrhea.

Gastrinomas

• Treatment • Medical Care • ► 1) Proton pump inhibitors (e.g. omeprazole, lansoprazole).

► 2) H2-receptor antagonists • The dose usually is 4-8 times higher than the dose administered to patients with peptic ulcer disease.

Gastrinomas • Treatment • Medical Care • 3) Chemotherapy

• This is indicated in patients with metastatic disease and in patients who are not candidates for surgery. • Chemotherapy reduces tumor size and improves the symptoms secondary to metastatic effects of the tumor.

Gastrinomas • Treatment • Surgical Care • Surgical care is indicated for localized disease. Surgical resection of localized disease leads to a complete cure without any recurrence in 20-25% of patients with gastrinomas.

Gastrinomas • Treatment • Surgical Care • Patients who have an isolated lesion or patients in whom the preoperative workup fails to localize the tumor should undergo laparotomy (by an experienced surgeon) with the intent to resect.

Gastrinomas • Consultations • Gastroenterologist • Endocrinologist • Oncologist • Surgeon

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