Effects of curative gastrinoma resection on gastric secretory function and antisecretory drug requirement in the Zollinger-Ellison syndrome

Abstract

The chronic hypergastrinemia in diseases such as the Zollinger-Ellison syndrome has trophic effects on the gastric mucosa, causing increased parietal cell mass reflected by increased maximal acid output (MAO) and basal acid output (BAO). The time course for the development of these gastric changes in humans is unknown, and controversy exists regarding whether reversal of the hypergastrinemia results in rapid normalization of gastric secretory function. To address these uncertainties, gastric secretory function was prospectively evaluated in 20 patients with the Zollinger-Ellison syndrome undergoing successful curative resection of gastrinoma. Each patient had gastric acid measurements, imaging studies, fasting serum gastrin and secretin provocative testing preoperatively, postoperatively at 3-6 months, and yearly thereafter. Preoperative mean BAO was 39 mEq/h, MAO 56 mEq/h, BAO-MAO ratio 0.73, and fasting gastrin output 1020 pg/mL. All patients were evaluated at 6 months, 17 at 1 year, 15 at 2 years, 13 at 3 years, and 9 at 4 years. By 3-6 months, MAO decreased by 50% in men (mean, 30 mEq/h) and by 35% in women (mean, 29 mEq/h) and then remained relatively unchanged for up to 4 years. Before surgery, 14 of 20 patients (70%) had an elevated MAO, whereas 4 years after resection, none of 9 patients had elevated levels. By 3-6 months, BAO decreased by 75% and remained unchanged for up to 4 years. At 3-6 months, 56% of patients were mild hypersecretors and 67% remained hypersecretors up to 4 years. Preoperatively, the BAO-MAO ratio was elevated in 16 of 20 patients (80%); postoperatively, only 5 of 18 patients (28%) at 3-6 months, 2 of 15 (13%) at 1 year, and 2 of 10 (20%) at 4 years continued to have elevated ratios. Preoperatively, the mean ranitidine dose was 1597 mg/day, whereas after surgery the mean dose was 535 mg/day at 3-6 months and approximately 300 mg/day at 1-4 years with 8 patients requiring no antisecretory drug. These results show that the trophic effects of chronic hypergastrinemia are, in general, rapidly reversible with a 50% decrease in MAO within 3-6 months of cure. Similarly, BAO decreased by 75% within 3-6 months. Despite these decreases, careful monitoring of acid secretion is required after reversal of the chronic hypergastrinemia in diseases such as the Zollinger-Ellison syndrome, because 55% of patients at 3-6 months and up to 67% at 4 years continue to remain mild hypersecretors and require low doses of antisecretory drugs.