Use of intraperitoneal 5-fluorouracil and chlorhexidine for prevention of recurrence of perforated colorectal carcinoma in a rat model.

Abstract

Colorectal cancer is a prevalent and mortal disease, resulting in nearly 55,000 deaths in the United States annually. Preoperative or intraoperative spillage of tumor cells because of perforation occurs in up to 10 percent of cases. When this spillage occurs, the chance of recurrence and death is dramatically increased. In an effort to reduce the chance of recurrence and death, we used a rat model to evaluate the efficacies of intraperitoneal 5-fluorouracil and chlorhexidine in reducing the incidence of recurrence. Rats were injected with 10 mg/kg azoxymethane subcutaneously weekly for 12 weeks to induce colorectal cancers. At 20 weeks, subtotal colectomies were performed on rats with colorectal tumors and without peritoneal implants or liver metastases. At the time of surgery, a cut portion of the tumor was placed in the abdomen for 30 minutes; the rats then randomly received peritoneal irrigation with 5-fluorouracil, chlorhexidine, or sterile water (control). Eight weeks postoperatively a necropsy was performed. At that time, obvious and suspected recurrences and the anastomotic area were sampled for histologic evaluation. Significant differences were seen with chlorhexidine vs. water for gross tumor (P = 0.05) and microscopic tumor (P < 0.05). 5-Fluorouracil showed a greater rate of abscess formation vs. both control and chlorhexidine (P > 0.05). Use of chlorhexidine intraperitoneal therapy at the time of the operation for perforated colorectal cancer significantly decreases the frequency of gross tumor recurrence but not total recurrences. Intraperitoneal 5-fluorouracil does not significantly decrease recurrence and may increase the risk of abscess when used intraoperatively.