Purpose: The alimentary tract demonstrates a remarkable ability to withstand injury by exogenous or elaborated endogenously luminal aggressive factors. Mucosal integrity peptides are pivotal in maintaining mucosal strength resisting the injury by the luminal chemical or physical insults. The leading peptide defining this strength is transforming growth factor α (TGFα), secreted by the esophageal submucosal glands as well as salivary glands that remain under control of serotonergic (5HT-4) pathway in humans (M. Majewski et al. Clin. Gastroenterol. Hepatol. 5:430-38, 2007). The rate of TGFα secretion, however, in patients with Barrett's esophagus (BE), setting the stage for the development of dysplasia and ultimately esophageal adenocarcinoma remains to be explored. Aims: 1. To test the rates of secretion of esophageal TGFα in patients with BE. 2. To compare these results with corresponding values recorded in asymptomatic volunteers.
Methods: The study was approved by IRB and conducted in 25 asymptomatic volunteers (12F & 13M, mean age of 40, range 23-59) and in 10 patients with the long segment (≥ 3.0 cm) of BE (2F & 7M, mean age of 49, range 30-69). Esophageal secretory function was explored using the esophageal perfusion catheter (Wilson Cook Med. NC) during the mucosal challenge with initial NaCl, HCl, HCl/Pepsin and final NaCl, mimicking the natural gastroesophageal reflux scenario. TGFα in esophageal secretions was measured using a commercially available RIA kit (Biomedical Technol. Stoughton, MA). Statistical analysis was performed using Σ-Stat (SyStat Inc., CA).
Results: The rate of TGFα secretion in patients with BE was 22% higher in basal conditions (mucosal exposure to initial saline) than in controls (0.61±0.08 vs. 0.50±0.05 ng/min). The rate, however, of TGFα secretion in patients with BE during mucosal exposure to HCl (pH 2.1) increased further, becoming 108% higher (statistically significant) than in controls (0.68±0.08 vs. 0.32±0.07 ng/min, p<0.05). The rate of esophageal TGFα secretion in patients with BE during mucosal exposure to HCl /pepsin and subsequent final saline remained also numerically higher than in controls.
Conclusion: 1. Significantly higher rate of esophageal TGFα secretion in patients with BE, especially during mucosal exposure to HCl, mimicking the natural gastroesophageal reflux scenario seems to indicate that the integrity of the intestinal metaplasia epithelium is profoundly challenged. 2. The role of this enhancing TGFα secretion phenomenon in the development of dysplasia and subsequent adenocarcinoma requires further investigation.