Zollinger-Ellison Syndrom - Pancreatic cancers
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Zollinger-Ellison Syndrom -(Z-E Syndrome; Gastrinoma)
Zollinger-Ellison syndrome is caused by a gastrin-producing tumor usually located in the pancreas or the duodenal wall. Gastric acid hypersecretion and peptic ulceration result. Diagnosis is by measuring serum gastrin levels. Treatment is proton pump inhibitors and surgical removal.
Gastrinomas occur in the pancreas or duodenal wall 80 to 90% of the time. The remainder occur in the splenic hilum, mesentery, stomach, lymph node, or ovary. About 50% of patients have multiple tumors. Gastrinomas usually are small (< 1 cm in diameter) and grow slowly. About 50% are malignant. About 40 to 60% of patients with gastrinoma have multiple endocrine neoplasia.
Symptoms and Signs
Zollinger-Ellison syndrome typically presents as aggressive peptic ulcer disease, with ulcers occurring in atypical locations (up to 25% are located distal to the duodenal bulb). However, as many as 25% do not have an ulcer at diagnosis. Typical ulcer symptoms and complications (eg, perforation, bleeding, obstruction) can occur. Diarrhea is the initial symptom in 25 to 40% of patients.
Diagnosis
The syndrome is suspected by history, particularly when symptoms are refractory to standard acid suppressant therapy.
The most reliable test is serum gastrin. All patients have levels > 150 pg/mL; markedly elevated levels of > 1000 pg/mL in a patient with compatible clinical features and gastric acid hypersecretion of > 15 mEq/h establish the diagnosis. However, moderate hypergastrinemia can occur with hypochlorhydric states (eg, pernicious anemia, chronic gastritis, use of proton pump inhibitors), in renal insufficiency with decreased clearance of gastrins, in massive intestinal resection, and in pheochromocytoma.
A secretin provocative test may be useful in patients with gastrin levels
< 1000 pg/mL. An IV bolus of secretin 2 μg/kg is given with serial measurements of serum gastrin (10 and 1 min before, and 2, 5, 10, 15, 20 and 30 min after injection). The characteristic response in gastrinoma is an increase in gastrin levels, the opposite of what occurs in those with antral G-cell hyperplasia or typical peptic ulcer disease. Patients also should be evaluated for Helicobacter pylori infection, which commonly results in peptic ulceration and moderate excess gastrin secretion.
Once the diagnosis has been established, the tumor(s) must be localized. The first test is abdominal CT or somatostatin receptor scintigraphy, which may identify the primary tumor and metastatic disease. Selective arteriography with magnification and subtraction is also helpful. If no signs of metastases are present and the primary is uncertain, endoscopic ultrasound should be performed. Selective arterial secretin injection is an alternative.
Prognosis and Treatment
Five- and 10-yr survival is > 90% when an isolated tumor is removed surgically, versus 43% and 25% respectively with incomplete removal.
Acid suppression: Proton pump inhibitors are the drugs of choice: omeprazole or esomeprazole 40 mg po bid. The dose may be decreased gradually once symptoms resolve and acid output declines. A maintenance dose is needed; patients need to take these drugs indefinitely unless they undergo surgery.
Octreotide injections, 100 to 500 μg sc bid to tid, may also decrease gastric acid production and may be palliative in patients not responding well to proton pump inhibitors. A long-acting form of octreotide can be used 20 to 30 mg IM once/mo.
Surgery: Surgical removal should be attempted in patients without apparent metastases. At surgery, duodenotomy and intraoperative endoscopic transillumination or ultrasound help localize tumors. Surgical cure is possible in 20% of patients if the gastrinoma is not part of a multiple endocrine neoplasia syndrome.
Chemotherapy: In patients with metastatic disease, streptozocin in combination with 5-fluorouracil or doxorubicin is the preferred chemotherapy for islet cell tumors. It may reduce tumor mass (in 50 to 60%) and serum gastrin levels and is a useful adjunct to omeprazole. Patients with metastatic disease are not cured by chemotherapy.
K. Ozaki, T. Yamagami, K. Nomura and I. Narama
Research Institute of Drug Safety, Setsunan University, Hirakata, Osaka, Japan (KO, IN); and Marupi Lifetech Co., Ltd., Ikeda, Osaka, Japan (TY, KN)
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