Dilated intercellular spaces of esophageal epithelium in nonerosive reflux disease patients with physiological esophageal acid exposure.
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.
Caviglia
Renato
R
Department of Digestive Diseases and Department of Pathology, Università Campus Bio Medico, Roma, Italy.
Ribolsi
Mentore
M
Maggiano
Nicola
N
Gabbrielli
Armando M
AM
Emerenziani
Sara
S
Guarino
Michele Pier Luca
MP
Carotti
Simone
S
Habib
Fortunéé Irene
FI
Rabitti
Carla
C
Cicala
Michele
M
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