Mo1290 THE EFFECT OF PIRFENIDONE FOR ESOPHAGEAL STRICTURE AFTER CIRCUMFEREENTIAL ESOPHAGEAL ENDOSCOPIC SUBMUCOSAL DISSECTION IN A PORCINE MODEL

Abstract

Esophageal stricture inevitably comes up after endoscopic submucosal dissection (ESD) for circumferential esophageal cancer. The effect of current preventive treatments has not been sufficient, although several studies have been reported in multifaceted methods. We focused on Pirfenidone, which is an oral antifibrotic drug commonly used for idiopathic pulmonary fibrosis. Our aim was to investigate the effect of Pirfenidone for preventing esophageal stricture after circumferential esophageal ESD in a porcine model. Eight four-months-old female three-way crossed (LWD) pigs were used for this study. Eight pigs underwent a 5cm-long circumferential ESD under general anesthesia on day 1. Two pigs were used as a control group. Pirfenidone was orally administrated (800mg/day) to 2 pigs and (1200mg/day) to 4 pigs for fourteen consecutive days. Biological tissues were sampled by using forceps on day 1, day 8 and day 15. The pigs were euthanized on day 15, followed by evaluations on esophageal stricture macroscopically and microscopically, and the expression of genes closely associated with the development of fibrosis. The esophageal contraction rate (%) was calculated in extracted specimens macroscopically. The contraction rate (%) was defined as 100 (A - B)/A, where A is the mean value of oral diameter and anal diameter each 2cm from the edge after ESD and B is the narrowest diameter of esophagus. Esophageal fibrosis was identified by Masson’s Trichrome staining microscopically. The expression of genes was evaluated on the messenger RNA (mRNA) levels of IL-6, IL-1β, TNFα, TGF-β1, CTGF, FGF2, EGF, collagen1 and αSMA by Real-Time RT-PCR method. The contraction rate was 61.1% in the control group, 67.8% in Pirfenidone (800mg/day) and 58.1% in Pirfenidone (1200mg/day) groups. Pirfenidone didn’t reduce the stricture rate. The pathological findings or the expression of genes showed no significant differences. In the control group, the expression levels of TGF-β1 reached the maximum value on day 8 and decreased on day15. Whereas the expression levels of CTGF, FGF2, EGF, collagen1 and αSMA escalated stepwise. We couldn’t demonstrate the effect of Pirfenidone for esophageal stricture after circumferential esophageal ESD in a porcine model. However, results of this study might include some beneficial information for our further study.