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Gastrinomas are gastrin-secreting neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that result in hypergastrinemia. This leads to excessive gastric acid secretion and the resultant clinical manifestations, such as refractory PUD (with sequelae like bleeding, perforation, and obstruction), gastroesophageal reflux disease, and diarrhea.1,2 Gastrinomas are associated with multiple endocrine neoplasia type 1 (MEN-1) in about 25% of cases and occur sporadically the other three-quarters of the time.2,3


In 1955, Zollinger and Ellison published a report of two patients with refractory jejunal ulcers and concomitant pancreatic islet cell tumors. They proposed a “clinical entity consisting of hypersecretion, hyperacidity, and atypical peptic ulceration associated with non-insulin-producing islet cell tumors of the pancreas.”4 In fact, at least 16 reports of similar cases were published between 1908 and 1952 (six of which were referenced by Zollinger and Ellison), but Zollinger and Ellison were the first to suggest that an ulcerogenic factor was being produced by the islet cell tumor.5,6 They erroneously speculated that this factor was glucagon, and it was not until 5 years later that Gregory and Tracy extracted gastrin from the pancreatic tumor of a patient with Zollinger–Ellison syndrome (ZES).7

During the first decade after Zollinger and Ellison’s landmark publication, more than 250 cases were described and a tumor registry was established. In Ellison and Wilson’s 1964 review of these cases, they recognized that there was a frequent occurrence of multiple tumors or liver metastases, and they concluded that a total gastrectomy was the best surgical option as definitive ulcer management.5,8 At the same time, Oberhelman9 was the first to report a duodenal, rather than pancreatic, location for gastrinomas. He advocated local excision of the tumor (including pancreaticoduodenectomy if necessary) rather than total gastrectomy.10 By the mid-1970s, the tumor registry included more than 800 patients, and the majority of morbidity and mortality for these patients was related to PUD. It was understood that gastrinomas commonly occurred at multiple sites and were difficult to localize, and therefore removing the target organ by total gastrectomy remained the preferred operation.5,11

This philosophy changed with the advent of H2-receptor antagonists. Several reports in the mid-1970s described successful reduction of gastric acid secretion in patients with ZES who were treated with metiamide or cimetidine.12-16 In 1978, McCarthy declared cimetidine to be an acceptable alternative to total gastrectomy.17 Refractory PUD became even less common in the proton-pump inhibitor era.18

With this paradigm shift to medical management of gastric acid secretion, survival became more dependent on tumor progression and metastatic disease rather than PUD sequelae, and the surgical goal became curative resection of the gastrinoma.19 However, localization remained a challenge. Preoperative CT scan, ultrasound, and angiography were neither sensitive nor specific, and intraoperative exploration ...

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