Gastric exocrine and endocrine cell morphology under prolonged acid inhibition therapy: Results of a 5-year follow-up in the LOTUS trial

R. Fiocca, L. Mastracci, S. E. Attwood, C. Ell, J. P. Galmiche, J. Hatlebakk, A. Bärthel, G. Långström, T. Lind, L. Lundell

Research output: Contribution to journalArticlepeer-review


Background Sustained acid inhibition with PPI stimulates gastrin secretion, exerting a proliferative drive on enterochromaffin-like cells (ECL cells) of the oxyntic mucosa. It may also accelerate development of gastric gland atrophy in Helicobacter pylori-infected individuals. Aims To evaluate gastric exocrine and endocrine cell changes in GERD patients randomised to laparoscopic antireflux surgery (LARS, n = 288) or long-term (5 years) esomeprazole (ESO) treatment (n = 266). Methods Antral and corpus biopsies were taken at endoscopy and serum gastrin and chromogranin A levels were assayed, at baseline and after 1, 3 and 5 years' therapy. Results Biopsies were available at each time point for 158 LARS patients and 180 ESO patients. In H. pylori-infected subjects, antral mucosal inflammation and activity improved significantly (P <0.001) and stabilised after 3 years on esomeprazole while no change in inflammation was observed after LARS. Oxyntic mucosal inflammation and activity remained stable on esomeprazole but decreased slightly over time after LARS. Neither intestinal metaplasia nor atrophy developed in the oxyntic mucosa. ECL cell density increased significantly after ESO (P <0.001), corresponding with an increase in circulating gastrin and chromogranin A. After LARS, there was a significant decrease in ECL cell density (P <0.05), accompanied by a marginal decrease in gastrin and chromogranin. Conclusions Antral gastritis improved in H. pylori-infected GERD patients after 5 years on esomeprazole, with little change in laparoscopic antireflux surgery patients, who acted as a control. Despite a continued proliferative drive on enterochromaffin-like cells during esomeprazole treatment, no dysplastic or neoplastic lesions were found and no safety concerns were raised. NCT 00251927.

Original languageEnglish
Pages (from-to)959-971
Number of pages13
JournalAlimentary Pharmacology and Therapeutics
Issue number10
Publication statusPublished - Nov 2012

ASJC Scopus subject areas

  • Pharmacology (medical)


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