title: Dilated intercellular spaces of esophageal epithelium in nonerosive reflux disease patients with physiological esophageal acid exposure.
abstract: OBJECTIVE
  It has been demonstrated that dilation of intercellular spaces of esophageal epithelium is a marker of tissue injury in GERD patients with a pathological esophageal acid exposure time. To evaluate the relationship among ultrastructural changes, acid esophageal exposure, and GERD symptoms, intercellular space diameters have been assessed in nonerosive reflux disease (NERD) patients with/without abnormal acid exposure time.
  
  
  METHODS
  Following a pharmacological wash-out, 20 NERD patients underwent upper endoscopy, esophageal manometry, and 24-h pH monitoring. Biopsies were taken at 5 cm above the lower esophageal sphincter and intercellular space diameters were measured on transmission electron microscopy photomicrographs. Seven asymptomatic controls underwent the same protocol.
  
  
  RESULTS
  Acid exposure time was in the normal range in all controls and in 11 patients (NERD pH-negative); it was abnormal in 9 patients (NERD pH-positive). Mean intercellular space diameter in NERD pH-negative and in NERD pH-positive patients was three times greater than in controls (1.45 and 1.49 microm vs 0.45, p < 0.001). Mean values of maximum intercellular spaces in all NERD patients were greater, two-fold or more, than those in controls (p < 0.001). No difference in mean and maximal space diameters was observed between NERD pH-positive and pH-negative patients.
  
  
  CONCLUSIONS
  Dilation of intercellular spaces is a feature of NERD patients, irrespective of esophageal acid exposure, and can be considered an objective, structural marker of GERD symptoms. Impaired esophageal mucosal resistance, even to small amounts of acid refluxate, plays a key role in the pathophysiology of NERD.
authors.affiliation: Department of Digestive Diseases and Department of Pathology, Università Campus Bio Medico, Roma, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Caviglia
authors.forename: Mentore
authors.initials: M
authors.lastname: Ribolsi
authors.forename: Nicola
authors.initials: N
authors.lastname: Maggiano
authors.forename: Armando M
authors.initials: AM
authors.lastname: Gabbrielli
authors.forename: Sara
authors.initials: S
authors.lastname: Emerenziani
authors.forename: Michele Pier Luca
authors.initials: MP
authors.lastname: Guarino
authors.forename: Simone
authors.initials: S
authors.lastname: Carotti
authors.forename: Fortunéé Irene
authors.initials: FI
authors.lastname: Habib
authors.forename: Carla
authors.initials: C
authors.lastname: Rabitti
authors.forename: Michele
authors.initials: M
authors.lastname: Cicala
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D004108:Dilatation, Pathologic; D004847:Epithelial Cells / Q000648:ultrastructure; D005110:Extracellular Space; D005260:Female; D005764:Gastroesophageal Reflux / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D013997:Time Factors