Hormonal and histologic changes observed with long-term use of proton-pump inhibitors do not seem to translate into an elevated risk for mucosal gland atrophy or cancer.

Prolonged use of proton-pump inhibitors (PPIs) has been associated with an increase in serum gastrin levels, which could drive proliferation of enterochromaffin-like (ECL) cells in the gastric mucosa and contribute to mucosal gland atrophy in the presence of Helicobacter pylori infection. Two recent studies evaluated the long-term effects of PPI use on gastric mucosa.

In a multicenter study, Fiocca and colleagues randomized 554 patients with chronic gastroesophageal reflux to receive 20 mg of esomeprazole daily or undergo laparoscopic antireflux surgery. Gastric biopsies and serum samples for gastrin and chromogranin A were taken at baseline and at 1, 3, and 5 years. Biopsies from each time point were available for 338 participants. In the esomeprazole arm, ECL cell hyperplasia increased between time points, mucosal inflammation decreased (only in those with H. pylori infection), and serum gastrin and chromogranin A levels increased moderately. No atrophy or intestinal metaplasia occurred. The authors concluded that despite moderate increases in gastrin and chromogranin A levels, 5 years of esomeprazole therapy did not cause dysplastic or neoplastic changes and decreased inflammation in patients with H. pylori infection.

Brunner and colleagues report the longest follow-up results to date of efficacy, safety, and tolerability in 142 patients who received pantoprazole for a mean of 9.2 years to treat peptic ulcers or reflux esophagitis. Gastric biopsies and serum gastrin levels were obtained at baseline, during healing (until week 12), every 6 months during the first 5 years, and annually during the subsequent 10 years. The ECL cell density increased moderately during the first 3 years and then stabilized. Investigators observed no clinically relevant changes in the gastric mucosa or increase in intestinal metaplasia. Serum gastrin levels rose to moderate levels and subsequently remained constant but showed high variability between patients. In patients with H. pylori infection, antral gastritis regressed after eradication of the infection. The authors concluded that maintenance therapy with pantoprazole for up to 15 years is well tolerated, with no evidence of increased risk for gastric cancer.

Comment: Both studies confirm that long-term PPI treatment increases serum gastrin levels and is associated with an increase in ECL cells. Serum gastrin levels rose to a moderate level early in treatment and then remained constant for the duration of follow-up. The absence of histologic evidence of intestinal metaplasia or other precancerous mucosal changes suggests that the risk for gastric cancer is probably not increased by PPI therapy. However, both of these prospective studies were small and underpowered to detect a small increase in risk.

Source: Journal Watch Gastroenterology