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Recent developments have led to a further appreciation of the various species of circulating gastrin and to provocative tests for the presence of the Zollinger-Ellison syndrome. Studies of serum gastrin levels, together with other studies of physiologic response, have suggested some possible roles of gastrin in the complex gastric acid hypersecretory state that frequently accompanies duodenal ulcer. Finally, investigations of exogenous and endogenous serum gastrin have provided a mechanism to examine the possible physiologic effects of this hormone.

It has now been well established that the ulcerogenic syndrome associated with non-beta islet cell tumors of the pancreas is due to excess gastrin release and consequent marked gastric acid hypersecretion. The clinical manifestations may be similar to, but are often more severe and recurrent than, common peptic ulcer. The diagnosis of gastrinoma in patients with this clinical syndrome can be established principally by demonstration of fasting hypergastrinemia, and by application of provocative tests with measurement of serum gastrin in response to intravenous calcium infusion, intravenous secretin injection and feeding of a standard meal. Gastrinomas are usually located within the pancreas, are often multifocal and metastatic, but may be primary in non-pancreatic sites. There is substantial heterogeneity in the molecular forms of circulating and gastrinoma gastrin. Although hypergastrinemia is characteristic of gastrinoma, serum gastrin levels may be increased in disorders other than gastrinoma. Techniques are available to document the presence of gastrin in islet cell tumors and, thereby, to establish these as gastrinomas.

Hypergastrinemia and gastric acid hypersecretion are the principal laboratory features of Zollinger-Ellison syndrome. Decision and cost-effectiveness analyses were employed in the present study to compare and contrast the diagnostic strategies of initial gastric analysis followed by secretin infusion test versus secretin infusion test alone in the evaluation of hypergastrinemia in patients suspected of having gastrinoma. The results of this study showed that 59 percent of patients with elevated serum gastrin values were either hypochlorhydric or achlorhydric. Application of decision analysis to either diagnostic strategy demonstrated that gastric analysis followed by secretin infusion test, if indicated, was superior in expected value than secretin infusion test alone. Likewise, in this group of patients, performance of gastric analysis in the outpatient setting prior to secretin infusion testing was financially more advantageous than performance of secretin infusion testing alone. These results also demonstrate the importance of performing gastric analysis prior to anticipated hospitalization for evaluation of suspected gastrinoma. Such testing would obviate unnecessary hospitalization and medical costs.

From 1971-1986, 24 patients were diagnosed as having Zollinger-Ellison syndrome (ZES) and 22 patients had laparotomy. Of this group, gross tumor was identified in 15 of 22 patients. Ten of 15 patients had resection of their gastrinomas with the specific aim of curing the disease. This group had responded favorably to either cimetidine or ranitidine before operation. Preoperative transhepatic portal venous sampling (PVS) with gastrin determinations was performed in six patients; three patients had this procedure twice. The tumor was correctly localized by PVS in five of six patients. In four of six patients, the tumor was easily found at surgery. In two of six patients (33%) PVS was vital to intraoperative decisions. Criteria for biochemical cure are normal periodic fasting gastrin and secretin infusion tests. Of the 10 patients who had resection for potential cure, two patients failed within 48 hours of surgery on the basis of an elevated fasting serum gastrin level in one patient and a positive secretin infusion test in the other patient. Eight patients were considered cured with follow-up from 6 months through 15 years. Of the eight cured patients, the tumors were located as follows: four were extraintestinal and extrapancreatic, four were in the duodenal wall, one patient had a tumor located in the uncinate process of the pancreas, and one tumor was located in a lymph node along the lesser curve of the stomach. Two patients had mobilization of the pancreas and duodenum for a "blind" pancreatoduodenectomy based on preoperative PVS (2 procedures each patient). In one patient a 3-mm gastrinoma was enucleated from the posterior uncinate process. The second patient had pancreatoduodenectomy with findings of two duodenal wall gastrinomas. Both patients remained cured of ZES beyond 2 years. It is concluded that PVS does indeed locate some tumors before operation, even those not easily found at surgery. ZES can be cured by an aggressive approach combining preoperative tumor localization and tumor resection. Of the eight patients biochemically and perhaps biologically cured, follow-up was greater than four years in five patients, greater than two years in two patients, and beyond six months in one patient.