Colonic anastomotic healing after preoperative chemo-radiotherapy in rat.
OBJECTIVE
To prevent micrometastasis at an earlier stage and to increase the lateral or circumferential tumor free margins, there is a rationale for neo-adjuvant chemo-radiotherapy in patients with colorectal cancer. In order to investigate the effects of such a protocol on colonic anastomotic healing, an experimental study resembling the clinical use of neo-adjuvant concomitant 5-FU+ irradiation treatment of colorectal cancer was conducted.


METHODS
Seventy-one male Wistar rats were divided into three groups: a control group (I) underwent left colon resection and primary anastomosis (n = 20); a sham-treated group (II, n = 20); and a study group (III) which received fractionated irradiation to the whole pelvis to a total dose of 22 Gy, 5.5 Gy per fraction, in four consecutive days with linear accelerator and concomitant intra-peritoneal 5-FU (20 mg/kg/day) for five consecutive days. The last fraction of irradiation and the last injection were given four and three days before colonic resection and anastomosis, respectively. Within each group one-half of the animals were anesthetized on the third postoperative day and one-half on the seventh postoperative day. Abdominal wound healing, intraperitoneal adhesions, anastomotic complications, and anastomotic bursting pressure measurements were recorded. Following these measurements the anastomotic segment was resected for hydroxyproline content, myeloperoxidase activity, and histopathological evaluation.


RESULTS
There were no differences in the abdominal wound healing, intraperitoneal adhesions, and anastomotic complications between groups. At three and seven days, the mean bursting pressures of the anastomoses were 36.5 mm Hg and 208 mm Hg in group I, 34.5 and 228 in group II, and 27 and 167 in group III, respectively (p < 0.01, group III vs both groups I and II on day seven). The burst occurred at the anastomosis in all animals tested on the third postoperative day, and one in group I (10%), none in group II, and four in group III (40%) on the seventh postoperative day.


CONCLUSIONS
Preoperative pelvic fractionated irradiation and concomitant 5-FU delays anastomotic healing.
Department of Surgery, Faculty of Medicine, University of Ankara, Turkey.
M A
MA
Kuzu
C
C
Köksoy
F H
FH
Akyol
D
D
Uzal
I T
IT
Kale
D000714:Anastomosis, Surgical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003082:Colectomy; D003106:Colon / Q000601:surgery*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D019583:Dose Fractionation, Radiation; D005472:Fluorouracil / Q000627:therapeutic use; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D020360:Neoadjuvant Therapy; D009195:Peroxidase / Q000378:metabolism; D011183:Postoperative Complications; D011300:Preoperative Care; D018714:Radiotherapy, Adjuvant; D051381:Rats; D017208:Rats, Wistar; D014945:Wound Healing
D000964:Antimetabolites, Antineoplastic; D009195:Peroxidase; D006909:Hydroxyproline; D005472:Fluorouracil