Background and MethodsThe role of surgery in patients with the Zollinger-Ellison syndrome is controversial. To determine the efficacy of surgery in patients with this syndrome, we followed 151 consecutive patients who underwent laparotomy between 1981 and 1998. Of these patients, 123 had sporadic gastrinomas and 28 had multiple endocrine neoplasia type 1 with an imaged tumor of at least 3 cm in diameter. Tumor-localization studies and functional localization studies were performed routinely. All patients underwent surgery according to a similar operative protocol, and all patients who had surgery after 1986 underwent duodenotomy. ResultsThe 151 patients underwent 180 exploratory operations. The mean (±SD) follow-up after the first operation was 8±4 years. Gastrinomas were found in 140 of the patients (93 percent), including all of the last 81 patients to undergo surgery. The tumors were located in the duodenum in 74 patients (49 percent) and in the pancreas in 36 patients (24 percent); however, primary tumors were found in lymph nodes in 17 patients (11 percent) and in another location in 13 patients (9 percent). The primary location was unknown in 24 patients (16 percent). Among the patients with sporadic gastrinomas, 34 percent were free of disease at 10 years, as compared with none of the patients with multiple endocrine neoplasia type 1. The overall 10-year survival rate was 94 percent. ConclusionsAll patients with the Zollinger-Ellison syndrome who do not have multiple endocrine neoplasia type 1 or metastatic disease should be offered surgical exploration for possible cure. (N Engl

We prospectively evaluated the initial presenting symptoms in 261 patients with Zollinger-Ellison syndrome (ZES) over a 25-year period. Twenty-two percent of the patients had multiple endocrine neoplasia-type 1 (MEN-1) with ZES. Mean age at onset was 41.1 +/- 0.7 years, with MEN-1 patients presenting at a younger age than those with sporadic ZES (p < 0.0001). Three percent of the patients had onset of the disease < age 20 years, and 7% > 60 years. A mean delay to diagnosis of 5.2 +/- 0.4 years occurred in all patients. A shorter duration of symptoms was noted in female patients and in patients with liver metastases. Abdominal pain and diarrhea were the most common symptoms, present in 75% and 73% of patients, respectively. Heartburn and weight loss, which were uncommonly reported in early series, were present in 44% and 17% of patients, respectively. Gastrointestinal bleeding was the initial presentation in a quarter of the patients. Patients rarely presented with only 1 symptom (11%); pain and diarrhea was the most frequent combination, occurring in 55% of patients. An important presenting sign that should suggest ZES is prominent gastric body folds, which were noted on endoscopy in 94% of patients; however, esophageal stricture and duodenal or pyloric scarring, reported in numerous case reports, were noted in only 4%-10%. Patients with MEN-1 presented less frequently with pain and bleeding and more frequently with nephrolithiasis. Comparing the clinical presentation before the introduction of histamine H2-receptor antagonists (pre-1980, n = 36), after the introduction of histamine H2-receptor antagonists (1981-1989, n = 118), and after the introduction of proton pump inhibitors (PPIs) (> 1990, n = 106) demonstrates no change in age of onset; delay in diagnosis; frequency of pain, diarrhea, weight loss; or frequency of complications of severe peptic disease (bleeding, perforations, esophageal strictures, pyloric scarring). Since the introduction of histamine H2-receptor antagonists, fewer patients had a previous history of gastric acid-reducing surgery or total gastrectomy. Only 1 patient evaluated after 1980 had a total gastrectomy, and this was done in 1977. The location of the primary tumor in general had a minimal effect on the clinical presentation, causing no effect on the age at presentation, delay in diagnosis, frequency of nephrolithiasis, or severity of disease (strictures, perforations, peptic ulcers, pyloric scarring). Disease extent had a minimal effect on symptoms, with only bleeding being more frequent in patients with localized disease. Patients with advanced disease presented at a later age and with a shorter disease history (p = 0.001), were less likely to have MEN-1 (p = 0.0087), and tended to have diarrhea more frequently (p = 0.079). A correct diagnosis of ZES was made by the referring physician initially in only 3% of the patients. The most common misdiagnosis made were idiopathic peptic ulcer disease (71%), idiopathic gastroesophageal reflux disease (GERD) (7%), and chronic idiopathic diar...