Histological evaluation of colonic anastomotic healing in the rat following preoperative 5-fluorouracil, fractionated irradiation, and combined treatment

Abstract

There is a growing interest in neoadjuvant chemo- and radiotherapy as a treatment modality for colorectal cancer which could affect mechanical and biochemical parameters of anastomotic healing. This study investigated the effect of such protocols on colonic anastomotic healing by evaluating the histopathological parameters. One hundred and sixty male Wistar rats were divided into six groups: a control group (I, n = 20), a saline group (II, n = 30) which received 1 ml NaC1 intraperitoneally, a sham-irradiated group (III, n = 20), a 5-fluorouracil (5-FU) group (IV, n = 30), which received 5-FU (20 mg/kg) intraperitoneally for 5 consecutive days, an irradiated group (V, n = 40) which received fractionated irradiation to the whole pelvis to a total dose of 22 Gy, 5.5 Gy per fraction on 4 consecutive days, and a concomitant 5-FU + irradiation group (VI, n = 20) which received 5-FU as in group IV and irradiated as in group V. All groups underwent left colonic resection with primary anastomosis, and the last fraction of irradiation and the last injection were given 4 and 3 days before the operation, respectively. Within each group one half of the animals were killed on the third postoperative day and the other half on the seventh postoperative day. After the resection of the anastomotic segments, histopathological examination was evaluated. Apposition of the wound edges of the mucosa and the muscularis were not affected by the therapy. The level of granulocytes was high, inflammatory exudate and necrosis persisted, granulation tissue formation was delayed, and the levels of macrophages and fibroblasts were low. We conclude that colonic anastomotic healing can be affected by the administration of preoperative chemotherapy, irradiation, and chemoirradiation.

Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats

“…All rats lost weight compared with baseline values during 5-FU administration and after the operation, which was statistically significant in the IV group. These results were concordant with reports from the literature [6,8,32] . Weight loss after 5-FU is related to anastomotic healing.…”

“…The burst pressure values of the anastomotic segments were measured in vivo on the 3rd and 7th PO days in rats receiving and not receiving 5-FU in this study, similar to that in the study by Kuzu et al [6] . Anastomotic burst pressures have been measured in vitro in most previous similar reports [8,22] .…”

“…The 500 mg/m 2 human dose is equal to the animal dose used in this study. A 3 d interval between the last day of chemotherapy and the surgical procedure was approved to reduce the strong side effects of chemotherapy [6,22] . Weight reductions were detected both during 5-FU injections and after surgery.…”

“…5-fluorouracil (5-FU) treatment has been accepted as standard chemotherapy for colorectal cancers for a long time. Recently, high recurrence rates, the presence of distant metastasis, the possibility of complete resection, and the removal of circulating tumour cells after curative resection of colorectal cancers constitute a new therapeutic approach known as neo-adjuvant chemotherapy [5][6][7] . While the integrity of anastomoses after colorectal cancer resection is an important parameter on mortality and morbidity, the effects of preoperative chemotherapy on wound healing and anastomoses are also important and have not been clearly outlined.…”

Comparison of Early Postoperative Enteral Nutrients versus Chow on Colonic Anastomotic Healing in Normal Animals

“…Many systemic and local factors contribute to the success or the failure of the gastrointestinal healing process. These include type of illness, patient age, bowel preparation prior to surgery, surgical technique, nutritional status of the patient, radiochemotherapy, preoperative pharmacological intervention, enteral nutrition and bowel rest [1,2]. Among these, the nutritional status of the patient is very important and may at times play a pivotal role in the patient's ability to heal.…”