Influence of Reflux and Central Adiposity on Intercellular Space in Squamous Esophageal Epithelium: ACG Obesity Award

Abstract

Purpose: Central adiposity is associated with esophageal inflammation, metaplasia and neoplasia independent of gastroesophageal reflux and BMI. Mechanisms by which central adiposity may potentiate esophageal inflammation and neoplasia remain incompletely understood. Our aim was to determine the esophageal squamous epithelium intercellular space diameter in patients with increased central adiposity, independent of esophageal reflux. Methods: Subjects who underwent clinically indicated ambulatory 24-hour pH impedance studies and endoscopy within 48 hours were prospectively recruited. Anthropometric measurements (height, weight, waist circumference, hip circumference) were obtained using standard methods. Biopsies were taken from the squamous mucosa 5 cm above the gastroesophageal junction (GEJ). The patients were divided into the four groups outlined in Table 1. 10 sections were then prepared from the squamous mucosal biopsies. Using a transmission electron microscopy, four images were obtained randomly at the basal and spinous layers. Then, using a computerized image analyzer, 10 transects were randomly drawn across perpendicular cell membranes with each transect no closer than 1 μm apart. The intercellular space (ICS) was calculated at these transecting lines using the software.Table 1: Demographic dataResults: Thirteen subjects were prospectively recruited. Four (33%) were males. Mean age (SD) was 43.4 (16.9). Group 2, (centrally obese without reflux), had a statistically significant larger ICS diameter than the control group (no central obesity, no reflux) (0.503 μm). The difference between the reflux group and control was 0.223 μm. There was no statistically significant difference between the ICS diameters of groups 2, 3, and 4. Our ICS difference between reflux and non-reflux patients was consistent with the data in the literature.Figure 1: Mean Intercellular SpaceConclusion: In this study, we found that subjects with increased BMI and central obesity but no evidence of pathologic reflux on ambulatory pH monitoring, had dilated ICS. The ICS in obese subjects was almost twice the size of the control group (normal BMI and no reflux). Moreover, this was similar to that of subjects with pathologic reflux in the absence of obesity (normal BMI and WHR). This change may potentially increase susceptibility of centrally obese subjects to epithelial injury, inflammation and neoplasia.