[Keratinocyte growth factor significantly improves healing of left-sided colon anastomoses]

Inadequate healing and consequent leakage from large bowel anastomoses are a significant cause of morbidity and mortality following large bowel surgery. Systemic application of KGF has been shown to promote mucosal healing in models of colitis in rats and mice. The aim of the present study was to evaluate the effect of systemic Keratinocyte Growth Factor (KGF) administration on healing of colonic anastomoses in rats. Sprague-Dawley rats underwent laparotomy, division of the left colon and sigmoideo-sigmoideostomy. KGF (5 mg/kg) or its vehicle were administered intra-peritoneally 12 hours prior to surgery, and then once daily until sacrifice (2, 4, 7, 12 and 21 days after surgery). Bursting pressure measurements, histologic evaluation, morphometric analysis, mucin and collagen staining and hydroxyproline measurements of the anastomotic site were performed. Administration of KGF significantly increased anastomotic bursting pressure on postoperative day 2, 4 and 7 by +34%, +49% and +19%, respectively but not on day 12 and day 21. Histology, mucin staining and measurements of the colonic crypt depth showed markedly less extended inflammation, increased acidic mucin content and a significantly thickened mucosal layer in the KGF treated group when compared to vehicle treated animals. Hydroxyproline content and collagen staining were not different between KGF and vehicle treated animals. We conclude that KGF promotes healing of colonic anastomoses in rats during a one week postoperative period. KGF may be acting to accelerate host reparative processes as well as to enhance protection of the anastomotic wound bed by increased epithelium proliferation, increased mucus production and reduction of the inflammatory activity at the anastomotic site.