title: Gastric histology in children treated with proton pump inhibitors long term, with emphasis on enterochromaffin cell-like hyperplasia.
abstract: BACKGROUND
  There are longstanding concerns that carcinoid tumours or atrophic gastritis might develop in children receiving proton pump inhibitors (PPIs) long term. In children, this has not been studied using stains sensitive and specific for enterochromaffin-like (ECL) cells.
  
  
  OBJECTIVE
  To evaluate gastric biopsies for ECL hyperplasia or gastric atrophy, in children treated long-term with PPIs.
  
  
  METHODS
  Synaptophysin and chromogranin immunostaining, biopsies read anonymised, blinded. Endocrine cell numbers graded according to Rindi and Solcia.
  
  
  RESULTS
  Of 130 children with gastro-oesophageal reflux disease (GERD), 65 had sequential gastric biopsies, starting at median 8.2 years (<1 to 17). Of the 65, 83% had GERD-predisposing conditions, mostly neurological impairment or repaired oesophageal atresia. Four hundred and fifty-eight tissue blocks (208 antrum, 250 body) were available from a mean of 5.8 endoscopies (2-14). Of 82 gastric body biopsies in 40 patients with ECL hyperplasia, 67 had grade 1 hyperplasia, 15 grade 2. Of the 40, nine had ECL hyperplasia before PPI use; all nine had received H2-receptor antagonists. Median duration of PPI use was 3.17 years in patients with ECL hyperplasia, 2.20 years in those without (P=0.16). Helicobacter pylori was present in four patients; two had ECL hyperplasia. PPI duration was >3 years in 24 patients. In nine patients who received H2-receptor antagonists, changes were present before PPI use. No patient had atrophic gastritis.
  
  
  CONCLUSIONS
  A high percentage of children (61%) receiving long-term PPI continuously for up to 10.8 years (median 2.84 years) develop minor degrees of ECL hyperplasia. This has no known clinical significance. Children on PPIs for this duration do not appear to develop atrophic gastritis or carcinoid tumours.
authors.affiliation: Division of Paediatric Gastroenterology, BC Children's Hospital and University of British Columbia, Vancouver, BC, Canada. hassale@sutterhealth.org
authors.forename: E
authors.initials: E
authors.lastname: Hassall
authors.forename: D
authors.initials: D
authors.lastname: Owen
authors.forename: W
authors.initials: W
authors.lastname: Kerr
authors.forename: T
authors.initials: T
authors.lastname: Sturby
authors.forename: P
authors.initials: P
authors.lastname: Richardson
authors.forename: H
authors.initials: H
authors.lastname: El-Serag
mesh_terms: D000293:Adolescent; D002276:Carcinoid Tumor / Q000139:chemically induced*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019861:Enterochromaffin-like Cells; D005757:Gastritis, Atrophic / Q000139:chemically induced*; D005764:Gastroesophageal Reflux / Q000188:drug therapy*; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced*; D007223:Infant; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D054328:Proton Pump Inhibitors