Effects of Preoperative Chemoradiotherapy on the Healing of Colonic Anastomosis with the Lapse of Operation Time in the Rat

Yun, Sung Su; Kim, Dong Sik; Kim, Chun Jik; Kim, Sang Woon; Kim, Jae Whang; Suh, Bo Yang; shim, Min Chul; Kwun, Kaing Bo; Sung, Un Ki

Abstract

PURPOSE
Preoperative chemoradiotherapy has become an important adjunct in the management of rectal cancer. But both systemic toxicity of chemotherapy and local effect of radiation interfere wound healing of intestinal anastomosis and ultimately may lead to anastomotic leak and septic complications. The purpose of this study is to determine the optimal time interval between preoperative chemoradiotherapy and anastmotic construction, and it was evaluated by security of anastomotic construction.
METHODS
One hundred and twenty male Sprague Dawley rats weighing approximately 250 g were randomly divided into 4 groups (Control group; n=40, Group 1; n=20, Group 2; n=20, Group 3; n=40). The control group (n=20) underwent anastomotic construction at 1 week after general anesthesia without preoperative chemoradiotherapy. The experimental animals (group 1, 2, 3) received preoperative chemoradiotherapy with 5 daily dose (20 mg/kg) of 5-fluorouracil and single dose of 1500 cGy radiation at the rectosigmoid junction under general anesthesia on the day after last dose of chemotherapy. And group 1~3 subsequently underwent a laparotomy to make anastomotic construction at 1 week (Group 1), 2 weeks (Group 2), and 3 weeks (Group 3; n=20) after completion of chemoradiotherapy. The security of anastomotic construction was determined by bursting pressure, tissue hydroxyproline content, gross and microscopic findings of anastomotic area at the 5th and 10th postoperative day after anastomotic construction. To evaluate systemic toxicity after che-moradiotherapy, serial body weight and alteration of CBC were measured in the control group (n=20) and Group 3 (n=20) without anastomotic construction.
RESULTS
At the 5th postoperative day, Mean bursting pressures of the all treated groups were lower than that of the control group (Control group; 88 23 mmHg, Group 1; 49 22 mmHg, Group 2; 56 17 mmHg, Group 3; 78 23 mmHg). The difference was not significant in the group 3 compared with the control group. Body weight decreased in the all treated animals. The mean body weight was lowest on the day 8 after completion of chemoradiotherapy and then it gradually increased. WBC and platelet counts also decreased in the all treated animals. WBC count was lowest on the day 1 and platelet count was lowest on the day 3 after completion of chemoradiotherapy. Mean hydroxyproline contents at the anastomotic sites in the all treated groups were higher than that of the control group, especially in the group 2 and 3. Similar histologic changes were observed in both group 3 and control group.
CONCLUSION
The results suggest that the optimal time interval for safe intestinal anastomosis after preoperative chemoradiotherapy is 3 weeks or later.