Dilated intercellular spaces and acid reflux at the distal and proximal oesophagus in patients with non-erosive gastro-oesophageal reflux disease

Aliment Pharmacol Ther. 2007 Mar 1;25(5):629-36. doi: 10.1111/j.1365-2036.2006.03237.x.


Background: Acid exposure of proximal oesophagus and dilated intercellular space diameters of oesophageal epithelium are relevant in the perception of gastro-oesophageal reflux.

Aim: To explain the relationship between gastro-oesophageal reflux disease symptoms, acid exposure and intercellular space diameter along the oesophageal epithelium and to assess time-related variability of intercellular space diameter.

Methods: Thirty-three non-erosive reflux disease (NERD), six erosive oesophagitis patients and 12 asymptomatic controls underwent oesophageal manometry and 24-h dual-channel oesophageal pH-monitoring following endoscopy. Biopsies were taken 5 cm above the LES and 10 cm below the UES, at comparable levels, as pH sensors. A total of 100 intercellular space diameters per patient/control were measured blindly at transmission electron microscopy. In 15 patients, the investigation was repeated after 1 year.

Results: In all NERD patients, acid exposure was higher at mid-proximal oesophagus (P < 0.01) and mean intercellular space diameters, at distal and mid-proximal oesophagus, was three- and twofold higher (1.5 and 0.82 micro m, respectively) compared with controls. Intra-patient intercellular space diameter values were stable over time, not overlapping with those of controls.

Conclusions: Dilation of intercellular space diameter occurs along the distal and proximal oesophageal epithelium in NERD patients and could be responsible for the enhanced perception of proximal acid reflux. This finding appears to be time-reproducible and to represent a sensitive, histopathological marker of NERD.

MeSH terms

  • Adult
  • Biopsy
  • Child
  • Child, Preschool
  • Esophageal Diseases / pathology*
  • Esophagoscopy
  • Female
  • Gastroesophageal Reflux / pathology*
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Microscopy, Electron
  • Middle Aged