Long-Term Omeprazole Treatment in Man: Effects on Gastric Endocrine Cell Populations

Abstract

36 patients with chronic gastric or oesophageal peptic ulceration (including 6 with antrectomy), resistant to high-dose ranitidine treatment for at least 3 months, were successfully treated with 40–60 mg of omeprazole daily for periods between 1 and 2 years. Fasting serum gastrin levels were monitored at regular intervals during therapy and multiple gastric mucosal biopsies were taken during gastroscopy every 3–6 months. Gastrin levels increased significantly during the first 6 months of therapy from a medium level of 81.5 to 206 pg/ml, a slight decrease was seen thereafter. In 10 patients investigated before the start of the treatment and after 1 and 2 years, the volume density of argyrophilic cells in the oxyntic mucosa increased from 0.43 ± 0.08 to 0.91 ± 0.14% during the first year; this change was statistically significant. No further increase was observed thereafter. No such difference could be demonstrated between a larger group of 18 patients investigated before and after 1 year of treatment with omeprazole (0.806 ± 0.1 vs. 0.93 ± 0.08%) and between a larger group of 22 untreated patients and 17 patients treated for 17–24 months with omeprazole (0.73 ± 0.1 vs. 0.86 ± 0.09%). The volume density of argyrophilic cells found in 8 patients with gastrinoma amounted to 1.37 ± 0.22%. No clusters of endocrine cells were found in omeprazole-treated patients. The D cell volume density in the antral mucosa decreased significantly during the first months of treatment, but steadily increased thereafter to reach pretreatmet values after 17 months. There was no change in G cell volume density under therapy. No changes in gastrin levels or oxyntic argyrophilic cells were observed in the antrectomized patients. It is concluded that the hyperplasia of argyrophilic cells observed in some patients during long-term omeprazole treatment is mediated by hypergastrinaemia.

Proton pump inhibitors and risk of gastric cancer: a population-based cohort study

“…The profound reduction in gastric acid secretion induced by PPIs leads to increased secretion of gastrin, and most PPI users have moderate hypergastrinaemia (Lamberts et al, 1988;Klinkenberg-Knol et al, 1994). Gastrin has trophic effects on the gastrointestinal mucosa, and hypergastrinaemia has been associated with an increased risk of gastric carcinoids, and gastric and colonic carcinomas (Havu, 1986;Laine et al, 2000;Gillen and McColl, 2001;Waldum et al, 2005;Kuipers, 2006), although recent results for PPI use and colorectal cancer risk are reassuring (Robertson et al, 2007;Yang et al, 2007;van Soest et al, 2008).…”

Rationale and efficacy of medical therapy for gastroesophageal reflux disease

“…Worthy of note here are the results of Creutzfeldt's group [81], who found no densitovolumetric changcs in the oxyntic cell population, even after up to 24 months of 20-60 mg day-', nor any changes in the direction of focal hyperplasia of enterochromaffin-like cells. Gastrin levels in these patients did not exceed the average of 206 pgml-', and rapidly reverted to normal values after drug discontinuation.…”

“…Finally, many papers have been published concerning the effect of omeprazole administration on the gastric endocrine cells [80][81][82]. Worthy of note here are the results of Creutzfeldt's group [81], who found no densitovolumetric changcs in the oxyntic cell population, even after up to 24 months of 20-60 mg day-', nor any changes in the direction of focal hyperplasia of enterochromaffin-like cells.…”

Gastrin and gastric cancer

“…The PPIs are very efficient drugs in inhibiting gastric acid secretion (67), but at the same time risky due to hypergastrinemia. Rather early, it was shown that PPI treatment induced ECL cell hyperplasia (68), which caused rebound acid hypersecretion (69). A decade later, it was reported that a period of PPI dosed to healthy individuals induced dyspepsia (70) probably due to rebound acid hypersecretion.…”