Consider when ulcer disease is severe, refractory to therapy, associated with ulcers in atypical locations, or associated with diarrhea. Tumors are usually pancreatic or in duodenum (submucosal, often small), may be multiple, slowly growing; >60% malignant; 25% associated with MEN 1, i.e., multiple endocrine neoplasia type 1 (gastrinoma, hyperparathyroidism, pituitary neoplasm), often duodenal, small, multicentric, less likely to metastasize to liver than pancreatic gastrinomas but often metastasize to local lymph nodes.

Omeprazole (or lansoprazole), beginning at 60 mg PO q A.M. and increasing until maximal gastric acid output is <10 mmol/h before next dose, is drug of choice during evaluation and in pts who are not surgical candidates; dose can often be reduced over time. Radiolabeled octreotide scanning has emerged as the most sensitive test for detecting primary tumors and metastases; may be supplemented by endoscopic ultrasonography. Exploratory laparotomy with resection of primary tumor and solitary metastases is done when possible. In pts with MEN 1, tumor is often multifocal and unresectable; treat hyperparathyroidism first (hypergastrinemia may improve). For unresectable tumors, parietal cell vagotomy may enhance control of ulcer disease by drugs. Chemotherapy or biologic therapy is used for metastatic tumor to control symptoms (e.g., streptozocin, 5-fluorouracil, doxorubicin, or interferon α); 40% partial response rate. Long-acting and radioactive somatostatin analogues and a combination of temozolomide plus capecitabine may produce regression or disease stabilization. VEGF antagonists and mTOR inhibitors are being tested.