title: Effect of elimination of acid reflux on epithelial cell proliferative activity of Barrett esophagus.
abstract: BACKGROUND
  Barrett esophagus (BE) is a premalignant condition resulting from chronic acid gastroesophageal reflux and is associated with increased epithelial cell proliferation. Elimination of acid reflux might decrease cancer risk by affecting cell proliferation in BE. The effect of elimination of acid reflux on epithelial cell proliferation in BE was studied.
  
  
  METHODS
  Forty-five patients with long segment Barrett esophagus were treated in a randomized 2-year follow-up study with either omeprazole 40 mg b.i.d. (OME) or ranitidine 150 mg b.i.d. (RAN) and were compared for the effect on epithelial cell proliferation. Biopsies were taken 3 cm above the GE junction and just below the Z-line, at 0, 3, 9, and 24 months. Epithelial cell proliferation was determined by in vitro labeling with 5-bromo-2-deoxyuridine and immunohistochemistry. Labeling indices (LI) were established for luminal and crypt epithelium separately. Ambulatory 24-h esophageal pH-metry was performed at 0 and 3 months. Comparisons were made for the timeframes 0-3 months, 3-24 months, and 0-24 months.
  
  
  RESULTS
  OME reduced mean acid reflux to 0.1 %/24 h, RAN to 9.4%. In the distal and the proximal biopsies, change in LI after 3 months was n.s. at either level for both treatments. In the distal biopsies (OME 22, RAN 23 patients) luminal LI increased significantly for RAN from 3 to 24 months (+12.64% month, mean area under the curve (AUC)), while that for OME remained stable, RAN versus OME P < 0.05. Crypt LI increased in both groups, only in RAN significantly so (+30.75% month), RAN versus OME n.s. In the proximal biopsies luminal LI at 24 months (OME 20, RAN 21 patients) had increased slightly but not significantly in RAN (+8.86% month), RAN versus OME n.s., whereas in the crypts LI in OME it had increased significantly (+28.80% month), OME versus RAN n.s.
  
  
  CONCLUSIONS
  Elimination of acid reflux resulted in a stabilization of luminal cell proliferative activity of Barrett epithelium in the distal esophagus, whereas this activity increased during continued acid reflux. Whether this finding has any implication for the cancer risk in Barrett esophagus remains to be seen.
authors.affiliation: Dept of Gastroenterology and Hepatology, University Hospital, Groningen, The Netherlands.
authors.forename: F T
authors.initials: FT
authors.lastname: Peters
authors.forename: S
authors.initials: S
authors.lastname: Ganesh
authors.forename: E J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: W J
authors.initials: WJ
authors.lastname: Sluiter
authors.forename: A
authors.initials: A
authors.lastname: Karrenbeld
authors.forename: A
authors.initials: A
authors.lastname: de Jager-Krikken
authors.forename: E C
authors.initials: EC
authors.lastname: Klinkenberg-Knol
authors.forename: C B
authors.initials: CB
authors.lastname: Lamers
authors.forename: J H
authors.initials: JH
authors.lastname: Kleibeuker
mesh_terms: D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D001706:Biopsy; D002455:Cell Division; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005753:Gastric Mucosa / Q000473:pathology; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000188:drug therapy; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008875:Middle Aged; D009853:Omeprazole / Q000627:therapeutic use*; D011446:Prospective Studies; D011899:Ranitidine / Q000627:therapeutic use*; D018709:Statistics, Nonparametric
chemical_list: D004791:Enzyme Inhibitors; D006635:Histamine H2 Antagonists; D011899:Ranitidine; D009853:Omeprazole