Influence of preoperative high-dose radiotherapy on postoperative outcome and colonic anastomotic healing: experimental study in the rat.

Abstract

Surgical treatment of rectal cancer is followed by local recurrence in up to 30 percent of cases. Recently, preoperative low-dose radiotherapy has been shown to improve both local recurrence rate and overall survival. Down-staging of locally advanced tumors, however, requires preoperative doses of at least 50 to 60 Gy. Most experimental studies investigating the effect of preoperative radiotherapy have made use of a single dose or a limited number of fractionated doses. Moreover, in most studies, both limbs of the anastomosis were irradiated, in contrast to clinical practice, in which one limb of the anastomosis consists of nonirradiated bowel. We studied the effect of a fractionated, clinically relevant scheme of high-dose preoperative radiotherapy on colonic anastomotic healing in the rat. Male Wistar rats randomly received 0, 40, 60, or 80 Gy of preoperative radiotherapy on one limb of the anastomosis only. Radiotherapy doses were validated with implanted dosimeters; before the start of radiotherapy, the cecum was fixed outside the radiation field. A clinically used fractionation scheme of 2 Gy per day, 5 days per week for 4 to 8 weeks was used. The day after radiotherapy completion, a side-to-side colorectal anastomosis was performed. Rats were killed 10 days after surgery. The following parameters were determined: presence of abscess or peritonitis, anastomotic complications (stenosis, leak, or dehiscence), intestinal obstruction, anastomotic bursting pressure, and anastomotic hydroxyproline content. No significant differences were found in peritonitis rate, anastomotic complications, anastomotic bursting pressure, or hydroxyproline content. Irradiated animals gained weight more slowly than the control group. In this rat model, preoperative high-dose radiotherapy using a clinically relevant fractionation scheme does not affect outcome or anastomotic healing when only one limb of the anastomosis is irradiated.