title: Gastric exocrine and endocrine cell morphology under prolonged acid inhibition therapy: results of a 5-year follow-up in the LOTUS trial.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Surgical and Morphological Sciences, University of Genoa, Genoa, Italy. fiocca@unige.it
authors.forename: R
authors.initials: R
authors.lastname: Fiocca
authors.forename: L
authors.initials: L
authors.lastname: Mastracci
authors.forename: S E
authors.initials: SE
authors.lastname: Attwood
authors.forename: C
authors.initials: C
authors.lastname: Ell
authors.forename: J-P
authors.initials: JP
authors.lastname: Galmiche
authors.forename: J
authors.initials: J
authors.lastname: Hatlebakk
authors.forename: A
authors.initials: A
authors.lastname: Bärthel
authors.forename: G
authors.initials: G
authors.lastname: Långström
authors.forename: T
authors.initials: T
authors.lastname: Lind
authors.forename: L
authors.initials: L
authors.lastname: Lundell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D053379:Chromogranin A / Q000097:blood; D019861:Enterochromaffin-like Cells / Q000378:metabolism / Q000473:pathology*; D064098:Esomeprazole / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000097:blood; D005764:Gastroesophageal Reflux / Q000150:complications / Q000188:drug therapy*; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D010535:Laparoscopy; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000897:Anti-Ulcer Agents; D053379:Chromogranin A; D005755:Gastrins; D054328:Proton Pump Inhibitors; D064098:Esomeprazole