Intercellular space volume is mainly increased in the basal layer of esophageal squamous epithelium in patients with GERD.

BACKGROUND/AIMS: At present, the dilation of esophageal intercellular spaces (ICS) is considered an early morphologic marker of acid damage in patients with GERD. Nevertheless, previous electron microscopic (EM) studies had focused only on the suprabasal layer of squamous epithelium or did not nearly specify which layer of squamous epithelium was studied. Therefore, we aimed to assess the volumetric amount of the ICS in all layers of SE in patients with GERD. METHODS: In this study, 48 patients were prospectively included (NERD = 18, ERD = 17; Barrett's esophagus = 5, controls = 8). All patients with ERD and NERD had typical reflux symptoms, as assessed by a valid GERD questionnaire. ICS volume was assessed by electron microscopy in the superficial, prickle cell, and basal layers of esophageal squamous epithelium using the method of Weibel. RESULTS: ERD was associated with increased ICS volume in the basal layer (LA-A, p = 0.038; LA-B, p = 0.005) and prickle cell layer (LA-A, p = 0.006; LA-B, p = 0.007) as compared to controls. Comparisons between NERD and ERD patients revealed more dilated ICS in the basal layer (LA-B, p = 0.007), prickle cell layer (LA-A, p = 0.008; LA-B, p = 0.001) and superficial layer (LA-B, p = 0.018) in patients with ERD. CONCLUSIONS: Not only the diameter but also the volume of the ICS is increased in patients with GERD. Furthermore, the dilation of ICS is present in all three layers of the SE, being more pronounced in the basal layer. These findings support the concept that the impairment of the esophagus begins in the deeper parts of the esophageal epithelium.

Interleukin-1beta and interleukin-8 expression correlate with the histomorphological changes in esophageal mucosa of patients with erosive and non-erosive reflux disease.

BACKGROUND: Gastroesophageal reflux disease (GERD) leads to endoscopic and histomorphological changes in the gastroesophageal (GE) mucosa. AIMS: To evaluate the expression of the cytokines interleukin-1beta (IL-1beta) and interleukin-8 (IL-8) in the GE mucosa in GERD patients and controls and to correlate the cytokine expression with the histomorphological parameters. METHODS: One hundred and fifteen patients, 48 with erosive reflux disease (ERD) and 41 with non-erosive reflux disease (NERD) with typical GERD-related symptoms, and 26 controls were included. Endoscopic and histological characterization of esophagitis was performed according to the Los Angeles and Ismeil-Beigi/Vieth criteria, respectively. Mucosal gene expression levels of IL-1beta and IL-8 were analyzed by real-time RT-PCR. RESULTS: ERD and NERD patients revealed significant higher levels of IL-1beta and IL-8 transcript levels in the cardia and esophageal mucosa than controls. The esophageal mucosa revealed elevated IL-8 (2.5- and 8.7-fold) and IL-1beta (4.1- and 7.8-fold) transcript levels in NERD and ERD, respectively. Histological analysis demonstrated a stepwise increase of dilatation of intercellular spaces and the degree of basal cell hyperplasia from controls, NERD towards ERD. Gene expression levels of both cytokines correlated with histology. CONCLUSIONS: ERD and NERD are associated with an induction of the proinflammatory cytokines IL-1beta and IL-8 that correlates with histomorphological changes in esophageal mucosa.