Beneficial effect of iloprost® on impaired colonic anastomotic healing induced by intraperitoneal 5-fluorouracil infusion

PURPOSE: 5-Fluorouracil is the most effective chemotherapeutic agent in the management of patients with systemic colorectal cancer. Studies in recent years discussed the gradually increasing benefits of 5-fluorouracil within adjuvant chemotherapy protocols after complete surgical resections. However, many studies also have demonstrated that 5-fluorouracil impairs wound-healing on colonic anastomoses. METHODS: In our experimental study, we examined the influence of intraperitoneal 5-fluorouracil on healing of colonic anastomoses and, also, attempted to discover whether Iloprost(R) (PGI(2) analog, a potent vasodilator with confirmed cytoprotectivity and inhibitor of thrombocyte aggregation) counteracts impaired wound-healing induced by 5-fluorouracil. A total of 80 Wistar-Albino male rats were separated into four groups. From the day of the operation, Group A received intraperitoneal saline solution, Group B received 20 mg/kg 5-fluorouracil intraperitoneally, Group C received 20 mg/kg 5-fluorouracil plus 2 mu g/kg Iloprost(R) intraperitoneally, and Group D received 2 mu g/kg Iloprost(R) intraperitoneally. Each group was divided into two subgroups, and both subgroups were killed on the third and seventh postoperative days, respectively. The subjects were measured for anastomose bursting pressures and tissue hydroxyproline levels, and wound-healing was evaluated histopathologically. Statistical evaluations among each group were made with Student's t-test and Pearson's chi-squared tests. RESULTS: Iloprost(R) had an accelerating effect on normal colonic anastomose wound-healing histopathologically, had no significant difference on bursting pressures and hydroxyproline levels, and significantly improved the impaired healing effect of 5-fluorouracil. CONCLUSIONS: Our study showed a positive effect of Iloprost(R) on the healing of colon anastomosis and, more importantly, if wound-healing is impaired by a chemotherapeutic agent, Iloprost(R) counteracts and reverses the effect.