The Open Surgery Journal, 2007, 1,1-6 1 1874-3005/07 2007 Bentham Science Publishers Ltd. The Effects of Irinotecan on the Healing of Colonic Anastomoses in Rats Manousos-Georgios Pramateftakis *,1 , Dimitrios Kanellos 1 , Haralampos Demetriades 1 , Ioannis Kanellos 1 , Ioannis Mantzoros 1 , Emmanouil Zacharakis 1 , Kalliopi Despoudi 1 , Stamatios Angelopoulos 1 , Georgios Koliakos 2 , Thomas Zaraboukas 3 and Dimitrios Betsis 1 1 4th Surgical Department, Aristotle University of Thessaloniki, “G. Papanikolaou General Hospital, 57010 Exohi, Thessaloniki, Greece 2 Biochemical Laboratory, Aristotle University of Thessaloniki, Greece 3 Histopathology Department, Aristotle University of Thessaloniki, Greece Abstract: Aim: The aim of this experimental study was to investigate the effects of intraperitoneally injected irinotecan on the healing of colonic anastomoses after colon resection. Methods: Thirty male Wistar rats were used. The rats were randomized into two groups of 15 rats each. Immediately after colonic anastomoses were performed, the rats were injected intraperitoneally with either 3 ml of 0.9% NaCl solution or ir- inotecan (3 mg/kg body weight) depending on their group. All rats were sacrificed on the eighth postoperative day. The anastomoses were examined macroscopically and histologically. The anastomotic bursting pressures were recorded. Results: Anastomotic dehiscence was noted in 3 rats of the irinotecan group. All anastomoses of the control group re- mained intact until sacrifice. The adhesion formation at the anastomotic sites and the average inflammatory cell infiltra- tion scores were significantly higher in the irinotecan group compared to the control group. The bursting pressures, the hydroxyproline tissue content, the fibroblast activity and the collagen deposition were significantly lower in the irinotecan group. Neoangiogenesis did not differ significantly between the groups. Conclusion: Irinotecan, when injected intraperitoneally, affects the healing of colonic anastomoses in rats. Keywords: Irinotecan, colonic anastomosis, healing. INTRODUCTION It is well documented that after colon resection for can- cer, the immediate, postoperative, intraperitoneal administra- tion of cytostatica induces the destruction of cancer cells that have been disseminated during the procedure. Furthermore, administration of such drugs inhibits regional recurrence and liver metastases [1, 2]. However, according to the results of previous experimental studies performed in our laboratory as well as those of other researchers, the immediate postopera- tive administration of cytostatica impairs wound healing of colonic anastomoses and results in a higher incidence of anastomotic failure after colon resection [3, 4]. Irinotecan is a new chemotherapeutic agent, recently introduced in the field of chemotherapy for colorectal cancer. Intraperitoneal injections of irinotecan have not been used in humans yet. So far, the effects of irinotecan on the healing of colonic anas- tomoses have not been assessed in detail [5]. The aim of this experimental study was to investigate the effect of irinotecan on colonic healing when injected intrape- ritoneally after colon resection. MATERIALS AND METHODOLOGY Thirty male Wistar rats, weighing between 120g and 168g, were used. All animals received humane care in *Address correspondence to this author at Antheon 1, Panorama 55236, Thessaloniki, Greece; Tel: 00302310314313; Fax: +30 2310 358000; E-mail: mpramateftakis@hotmail.com accordance with the "Principles of Laboratory animal Care" formulated by the National Society for Medical Research and the "Guide for the Care and Use of Laboratory Animals" prepared by the Institute of Laboratory Animal Resources and published by the National Institute of Health (NIH Pub- lication No. 86-23). Principles of laboratory animal care were followed and the research protocol described was ap- proved by the Ethical Committee of the Department of Vet- erinary Services of the Prefecture of Thessalonica according to the Greek Law on the protection of animals. Animals were housed individually and had unrestricted access to the stan- dard laboratory diet and water pre- and post-operatively. Anaesthesia and Operative Technique The rats were weighed on the day of the operation as well as before the sacrifice. Changes in weight were recorded. Surgery was performed through a 3-cm midline incision un- der intraperitoneal thiopental anaesthesia (50 mg/kg body weight). A 1 cm long segment was resected out of the middle transverse colon and an end-to-end anastomosis was per- formed with eight interrupted sutures (6/0 polypropylene). Mass closure of the abdominal muscle layer and the skin was performed using three sutures (3/0 silk). Groups During the operation the rats were randomized to one of two groups of 15 rats each. Randomization was through the use of computer-generated random numbers and there was allocation concealment after randomization. Immediately after the formation of the colonic anastomoses, the rats in the