Background: The majority of patients with Zollinger–Ellison syndrome require lifelong treatment with proton pump inhibitors. Aims: To determine the efficacy of lansoprazole control of acid and pepsin secretion over the long term in Zollinger–Ellison syndrome and non‐Zollinger–Ellison syndrome hypersecretors. Methods: Sixty‐three hypersecretors (basal acid output > 15 mmol/h), 46 Zollinger–Ellison syndrome and 17 non‐Zollinger–Ellison syndrome, with a total history of 15.4 and 19.2 years, respectively, were entered into a long‐term prospective study using lansoprazole. Sixty‐one were studied every 3 months for 1 year and then every 3–6 months up to 10 years during lansoprazole treatment with endoscopy, serum gastrin and gastric analysis, measuring both basal and stimulated pH and acid and pepsin secretion. Doses were individually optimized and adjusted to keep the basal acid output at < 5 mmol/h in intact patients and < 1 mmol/h in antrectomized Zollinger–Ellison syndrome patients. Results: The dose of lansoprazole could not be predicted a priori from pre‐treatment acid or pepsin output, serum gastrin, prior omeprazole dose or diagnosis or prior complications. The median dose was ∼ 80 mg/day, with a wide range from 15 mg every other day to 360 mg/day, and generally stabilized by 12 months. However, as doses were adjusted over time for indications, almost half the patients required higher doses. With adjustments, the basal acid output was maintained in the target range in > 90% of intact patients and in 80% of antrectomized patients. Gastric juice pH increased from ∼ 1.2 before therapy to > 3.4 during therapy. Serum gastrin in Zollinger–Ellison syndrome patients, after excluding five outliers, did not change over the course of therapy, but doubled in non‐Zollinger–Ellison syndrome patients. There were no adverse events due to lansoprazole, and routine laboratory studies remained normal. Conclusions: The dose of lansoprazole for hypersecretors cannot be predicted, and thus needs to be optimized empirically on an individual basis. With continued periodic adjustments, almost half the patients required increased doses, while safe dose reduction was possible in only one‐quarter. When individually optimized, lansoprazole proved to be safe and effective in the control of secretion for the treatment of both Zollinger–Ellison syndrome and non‐Zollinger–Ellison syndrome hypersecretors for up to 10 years.

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Background: Helicobacter pylori infection may increase or decrease acid secretion and may augment proton pump inhibitor efficacy. Pepsin effects have not been reported. In Zollinger–Ellison syndrome (ZE) specifically, H. pylori has been reported to decrease acid. Aim: To examine H. pylori effects on secretion and dose of medication in hypersecretors (basal acid output > 15 mmol/h) undergoing long‐term treatment with individually optimized lansoprazole doses. Methods: Sixty‐five patients (47 ZE and 18 non‐ZE), treated for > 3 months to 10 years, were tested every 6 months with endoscopy, gastric analysis and serum gastrin. Results: Forty‐three per cent were H. pylori‐positive. Acid, pepsin and gastrin were not different between H. pylori‐positive and H. pylori‐negative patients before or during long‐term lansoprazole treatment. Initially, H. pylori‐positive patients required less lansoprazole than H. pylori‐negative patients (68 ± 6 vs. 96 ± 8 mg/day), but after 3 years the doses converged (83 vs. 86 mg/day). The disappearance of H. pylori in 15 patients caused no significant changes in acid, pepsin, gastrin or lansoprazole dose in the following 4 years. Conclusions: H. pylori had no significant initial or long‐term physiological or potential clinical effects on acid or pepsin secretion or gastrin in these acid hypersecretors.