Keratinocyte growth factor promotes healing of left-sided colon anastomoses

Abstract Background: Inadequate healing and consequent leakage from bowel anastomoses are a significant cause of postoperative morbidity and mortality. Systemic application of keratinocyte growth factor (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 KGF administration on healing of colonic anastomoses in rats. Methods: Rats underwent laparotomy, division of the left colon, and sigmoido-sigmoidostomy. KGF (5 mg/kg) or vehicle were administered intraperitoneally in two groups (n = 30 per group) 12 hours prior to surgery, and then once daily until sacrifice (6 animals per group; 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. Results: Administration of KGF significantly increased anastomotic bursting pressure on postoperative days 2, 4, and 7 by 34%, 49%, and 19%, respectively. Histology, mucin staining, and measurements of the colonic crypt depth showed markedly less extended inflammation with an increased acidic mucin content and a significantly thickened mucosal layer in the KGF treated group when compared with vehicle-treated animals. Conclusions: KGF promotes healing of colonic anastomoses in rats during a 1-week postoperative period following large bowel surgery. KGF may be acting to accelerate host reparative processes as well as to enhance protection of the anastomotic wound bed by increased colonic epithelium proliferation, increased mucus production, and reduction of the inflammatory activity at the anastomotic site.