Original Contribution
The American Journal of Gastroenterology (2005) 100, 543–548; doi:10.1111/j.1572-0241.2005.40978.x
Dilated Intercellular Spaces of Esophageal Epithelium in Nonerosive Reflux Disease Patients with Physiological Esophageal Acid Exposure
Renato Caviglia MD, PhD1, Mentore Ribolsi MD1, Nicola Maggiano MD, PhD1, Armando M Gabbrielli MD1, Sara Emerenziani MD1, Michele Pier Luca Guarino MD1, Simone Carotti MD1, Fortunéé Irene Habib MD1, Carla Rabitti MD1 and Michele Cicala MD, PhD1
1Department of Digestive Diseases and Department of Pathology, Università Campus Bio Medico; Department of Pathology, Università Cattolica del Sacro Cuore; and Department of Clinical Science, Università La Sapienza, Roma, Italy
Correspondence: Michele Cicala, MD, PhD, Digestive Disease Department, Campus Bio Medico University, Via Longoni, 83, 00155 Rome, Italy
Received 15 June 2004; Revised 0000; Accepted 8 September 2004.
Abstract
OBJECTIVES:
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 
m 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.
