DIMINISHED LUMINAL RELEASE OF ESOPHAGEAL EPIDERMAL GROWTH-FACTOR IN PATIENTS WITH REFLUX ESOPHAGITIS

Objectives: It has recently been demonstrated that human esophageal mu cosa, containing numerous submucosal mucous glands, has the ability to elaborate significant amounts of esophageal epidermal growth factor ( eEGF). Because of its role in the maintenance of the integrity of the esophageal mucosa, we elected to study the rate of secretion of eEGF i n patients with reflux esophagitis (RE), compared with controls, using our newly developed esophageal perfusion model. Methods: Fourteen hea lthy asymptomatic volunteers and 14 patients with endoscopically confi rmed esophagitis underwent esophageal perfusion with saline, HCl (0.01 M, pH 2.1) HCl/pepsin (0.5 mg/ml of HCl), and ending NaCl solution du ring four consecutive 8-min perfusion periods. All perfusates were ass ayed for EGF by RIA (Amersham). Results are expressed as mean +/- SEM. Student's t test was used for statistical analysis. Results: The basa l rate of luminal EGF release in patients with RE was 3.78 +/- 0.29 ng /min. This value significantly declined (2.27 +/- 0.27 ng/min; p < 0.0 01) during mucosal exposure to HCl but was significantly enhanced when the HCl perfusing solution was supplemented with pepsin (4.20 +/- 0.2 9; p < 0.001 vs. HCl). Introduction of saline during the last perfusio n period maintained a rate of luminal EGF release similar to that obse rved during the initial esophageal perfusion with saline. Luminal rele ase of EGF in patients with RE was significantly lower, compared with corresponding values recorded in controls during perfusion with saline (3.78 +/- 0.29 vs. 14.1 +/- 1.25 ng/min; p < 0.00001), with HCl (2.27 +/- 0.27 vs. 5.95 ng/min; p < 0.0001), with HCl/pepsin solution (4.2 +/- 0.29 vs. 11.7 +/- 1.88 ng/min; p < 0.0001), and during the final p erfusion period with saline (3.73 +/- 0.25 vs. 15.1 +/- 1.1 ng/min; p < 0.00001). Therefore, the rate of luminal EGF release in controls was 4-fold, 3-fold, 3-fold, and 4-fold higher than that of patients with RE during perfusion with initial saline, HCl, HCl/pepsin, and final sa line, respectively. Conclusions: 1) Decreased esophageal EGF in patien ts with RE may facilitate the development or delay the healing of muco sal injury. 2) Depletion of EGF from the mucus layer covering the epit helium under the impact of refluxed luminal acid/pepsin may be conside red as one of the potential underlying mechanisms leading to damage of the esophageal mucosa during gastroesophageal reflux episodes.