title: Dilated intercellular spaces as a marker of oesophageal damage: comparative results in gastro-oesophageal reflux disease with or without bile reflux.
abstract: BACKGROUND
  The dilation of oesophageal intercellular spaces, clearly apparent in transmission electron microscopy images, is a marker of cellular damage induced by acid.
  
  
  OBJECTIVE
  To analyse the presence of dilated intercellular spaces and to quantify the scores in controls and in patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux accompanied by erosive or non-erosive reflux disease.
  
  
  METHODS
  Thirty-eight symptomatic patients with gastro-oesophageal reflux disease or duodenal gastro-oesophageal reflux and 12 asymptomatic controls, classified on the basis of pH-metry and bilimetry, underwent endoscopy. Six tissue biopsies were taken from the normal mucosa for light microscopy and transmission electron microscopy evaluation. Dilated intercellular spaces were measured on photomicrographs of the specimens (at least 100 transects were measured for each patient).
  
  
  RESULTS
  Twenty-two patients with gastro-oesophageal reflux disease had normal macroscopic mucosa but, at histology, five patients with erosive gastro-oesophageal reflux disease had mild oesophagitis and one had moderate oesophagitis. Seven patients with duodenal gastro-oesophageal reflux had normal mucosa, whilst three with erosive duodenal gastro-oesophageal reflux had mild oesophagitis at histology. At transmission electron microscopy, all controls had dilated intercellular spaces of less than 1.69 microm. Each symptomatic patient had a mean dilated intercellular space value and a mean value of the maximum dilated intercellular space at least three or more times greater than that in controls (P < 0.001). No statistical differences were observed between erosive and non-erosive oesophagitis.
  
  
  CONCLUSIONS
  The dilated intercellular space is an extremely sensitive marker of damage in gastro-oesophageal reflux disease, duodenal gastro-oesophageal reflux and non-erosive reflux disease, and serves as the most appropriate marker of damage evaluation in non-erosive reflux disease reported to date. A mean dilated intercellular space of 0.74 micro m provides a cut-off score for damage. No quantitative or qualitative differences in dilated intercellular space scores were found between pure and mixed acid reflux.
authors.affiliation: Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy. calabrese.c@med.unibo.it
authors.forename: C
authors.initials: C
authors.lastname: Calabrese
authors.forename: A
authors.initials: A
authors.lastname: Fabbri
authors.forename: M
authors.initials: M
authors.lastname: Bortolotti
authors.forename: G
authors.initials: G
authors.lastname: Cenacchi
authors.forename: A
authors.initials: A
authors.lastname: Areni
authors.forename: C
authors.initials: C
authors.lastname: Scialpi
authors.forename: M
authors.initials: M
authors.lastname: Miglioli
authors.forename: G
authors.initials: G
authors.lastname: Di Febo
mesh_terms: D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D001655:Bile Reflux; D015415:Biomarkers; D004108:Dilatation, Pathologic; D016099:Endoscopy, Gastrointestinal; D004935:Esophageal Diseases / Q000473:pathology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000473:pathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged
chemical_list: D015415:Biomarkers