The Relationship Between Dilated Intercellular Spaces And The Symptoms Of Non-erosive Reflux Disease

Objectives Recent studies have demonstrated that the electron microscope or optical microscope can identify the dilated intercellular spaces (DIS) which may be the morphological signs of esophageal epithelial injury in non-erosive reflux disease patients. But little is known about the relationship between the DIS and the symptoms of Non-erosive reflux disease (NERD). Factors that led to DIS are not very clear. The aim of this study is to investigate the relationship between different symptoms of NERD and esophageal squamous DIS, and the relationship between Gastroesophageal reflux types and DIS.Methods Forty-nine patients diagnosed with NERD and 12 healthy volunteers were involved in this study. According to the symptom, Patients were divided into three groups: A: 15 Patients with symptoms of heartburn and regurgitation; B: 17 patients with Chest pain and regurgitation; C: 17 patients with extra-esophageal symptoms and regurgitation. All subjects were underwent endoscope and biopsies were taken in both 5 cm above the LES and 10 cm below the UES, DIS were assessed blindly at light microscopy. 23 and 22 NERD patients were respectively underwent high-resolution manometry (HRM) and multi-channel intralumminal impedance-PH (MII-PH) following endoscopy.Results The intercellular spaces of proximal and distal esophagus were no differences in all groups. The intercellular spaces both in proximal and distal were significant higher in patients with NERD than in healthy subjects (1.20±0.61 vs. 0.50±0.18, 1.18±0.49 vs.0.54±0.15,P<0.001). The proximal and distal intercellular spaces in A and B group were significantly higher than in C group(1.30±0.60;1.42±0.74 vs. 0.91±0.31, P<0.05 and 1.31±0.64 ;1.31±0.46 vs. 0.94±0.21 P<0.05, respectively)The proximal and distal intercellular spaces between patients with normal and abnormal esophageal motor function were no differences(1.23±0.66 vs.1.24±0.79 ; 1.17±0.52 vs.1.42±0.59 P> 0.05 ) .The distal intercellular spaces between patients with abnormal acid reflux were significantly higher than normal(1.76±0.62 vs. 1.11±0.48,P<0.05).Conclusion DIS is a minimal change of esophageal epithelial injury in GERD patients. It may be the morphological signs inducing the symptoms of heartburn and chest pain in GERD. The mechanism of extra-esophageal symptoms in GERD may be more complex except DIS. DIS maybe a new method to diagnose of NERD in clinical practice.