The Potential Pathogenetic Role of Esophageal Prostaglandins in Patients with Barrettʼs Esophagus: Its Clinical Implication: Presidential Poster

Abstract

Purpose: The majority of patients with chronic symptoms of gastroesophageal reflux disease (GERD) are likely to never develop endoscopic esophagitis. This patient's population is known under acronym NERD, i.e. negative endoscopically reflux disease. On the other side of the wide GERD spectrum, there is a small subpopulation evolving into Barrett's esophagus (BE) dysplasia and adenocarcinoma. Prostaglandin E2 generated through the cyclooxygenase I (COX-I) pathway is protective towards the columnar epithelium, however, its very high levels elaborated by COX-II seem to promote the malignant potential within the intestinal metaplasia (Lewis et al. Surg Endosc, 2011). Little is known, however, regarding the rate of luminal release of PGE2 in patients with BE as compared to subjects with NERD. The following specific aims were designated to our study protocol: 1.) To measure the rate of PGE2 generation in esophageal secretion in patients with BE, and 2). to compare obtained results with corresponding values recorded in NERD patients. Methods: The study, approved by IRB, was conducted in 10 patients with the long segment (>3cm) of BE (2 female [F] and 8 male [M], mean age of 49 years, 30-69 range), and in 10 patients with a long history of NERD (4F and 6M, mean age of 40, 27-64 range). The esophageal secretions from the mucosa and submucosal mucous glands were collected during mucosal exposure to initial NaCl followed by HCl/Pepsin (HCl/P) and final saline, mimicking the natural gastroesophageal reflux scenario, using a specially designed esophageal perfusion catheter (Wilson Cook Med. NC). In collected samples PGE2 was measured using RIA (Amersham, MA). Statistical analysis was performed using Σ-Stat (SPSS, IL). Results: The basal rate of esophageal PGE2 secretion in patients with BE during exposure to saline was (Mean, ±SEM) 7.2-fold higher than in patients with NERD (9622 ±4164 vs. 1332 ±441 pg/min, P<0.01). Furthermore, the rate of esophageal PGE2 secretion in BE patients remained also 5.8-fold higher than in NERD patients during exposure to HCl/P (4030 ±1748 vs. 695 ±203 pg/min, P<0.05). Esophageal PGE2 secretion in BE patients remained also 10.4-fold higher than in NERD patients during the ending mucosal perfusion with saline (5716 ±2656 vs. 551±180 pg/min, P<0.05). Conclusion: 1.) Profoundly lower rate of esophageal PGE2 generation in patients with NERD confirms that equilibrium between aggressive factors and protective mechanisms within the esophageal squamous mucosa is well preserved. 2.) Several fold higher rate of esophageal PGE2 secretion in BE may imply that the development of the columnar epithelium of BE could potentially be driven by excessive generation of prostaglandins in mucosal inflammatory changes, potentially setting the stage for further complications.