Paper
Letter: proton pump inhibitors, hypergastrinaemia and the risk of gastric neoplasia
Published Aug 1, 2015 · Helge L. Waldum, Ø. Hauso, R. Fossmark
Alimentary Pharmacology & Therapeutics
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Abstract
SIRS, We read with interest the paper by Attwood and coworkers on the safety of proton pump inhibitor (PPI) therapy, based upon the SOPRAN and LOTUS studies, with median PPI exposures of 12 and 5 years respectively. Fasting gastrin doubled in both studies and chromogranin A doubled in the LOTUS study. No difference in gastric neoplasia (including cysts and polyps) was detected. For several reasons we are not surprised: carcinogenesis takes time and cancer occurs particularly in older people. PPIs have a steep concentration – effect curve and most patients in the two studies used a rather low dose. In addition, Helicobacter pylori infection increases the degree of hypergastrinaemia during PPI use, 4 but few patients were infected. Women develop higher gastrin values during PPI treatment, but in the LOTUS study, 75% of PPI-treated patients were males. Finally, as the studies were not even able to detect any evidence of a PPI-induced increase in fundic gland polyps, the quality of the endoscopies and the ability to detect carcinoids in the SOPRAN and LOTUS studies is questionable. Although PPI treatment as a cause of gastric neoplasia has been denied by many, Astra reported the occurrence of enterochromaffin-like cell (ECL)-derived tumours in patients on long-term PPI treatment, as have we and others. Curiously, Attwood used our paperas an argument against a role of PPI in the development of ECL cell carcinoids. The ECL is the target cell of circulating gastrin and plays an important role in gastric carcinogenesis. Helicobacter pylori is accepted as the main cause of gastritis, and an important cause of gastric cancer, and recently we described that gastrin could be the pathogenetic factor. In conclusion, PPIs seem rather safe with respect to neoplasia in older people, but the risk associated with lifelong treatment of young patients cannot be neglected.
Rigorous JournalPPIs appear safe for older patients with no significant increase in gastric neoplasia, but the risk of lifelong treatment for young patients remains.
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