Antifibrotic Effect of the TGF-β Type I Receptor Inhibitor EW-7197 on Anastomotic Healing in a Rat...

Background/Aim: Anastomotic stricture following choledochojejunostomy (CJS) is largely driven by fibrotic remodeling at the anastomotic site, a process mediated by transforming growth factor-β (TGF-β) signaling. This problem is particularly relevant in emergency biliary surgery, where CJS is frequently performed under suboptimal conditions and anastomotic leakage is common, predisposing to exaggerated fibrosis and late strictures. This study aimed to evaluate the effect of the TGF-β type I receptor (ALK5) inhibitor EW-7197 (vactosertib) on histopathological parameters of anastomotic healing, with a particular focus on fibrosis, in a rat CJS model. Materials and Methods: Twenty-four male Wistar Albino rats were randomized into three groups (n = 8 each): control (G1), CJS only (G2), and CJS plus EW-7197 (G3). EW-7197 was administered as a single intraperitoneal dose (20 mg/kg) immediately after completion of the anastomosis. On postoperative day 21, choledochojejunal anastomotic tissues were harvested and evaluated histologically using hematoxylin-eosin and Masson's trichrome staining. Edema, hyperemia, inflammation, and fibrosis were graded using a semi-quantitative scoring system, and intergroup comparisons were performed using non-parametric statistical tests. Results: Compared with surgery alone, EW-7197 treatment resulted in a statistically significant reduction in fibrosis severity at the anastomotic site (p < 0.001) and a significant attenuation of hyperemia (p = 0.007). Edema scores showed a downward trend in the EW-7197-treated group but did not reach statistical significance, while inflammation scores did not differ significantly between the surgical groups. Conclusions: In this experimental rat choledochojejunostomy model, administration of the selective ALK5 inhibitor EW-7197 significantly reduced histopathological fibrosis and hyperemia at the anastomotic site on postoperative day 21 without affecting inflammation severity. These findings support the role of the TGF-β/Smad pathway in bilioenteric anastomotic fibrotic remodeling. However, further studies including molecular validation and functional assessments are required to clarify the translational relevance of these results.