Healing of experimental colonic anastomoses: effects of combined preoperative high-dose radiotherapy and intraperitoneal 5-fluorouracil.
To study the effects of preoperative radiochemotherapy (RCT) on the healing of colonic anastomosis, the rectosigmoid colon in male Wistar rats was irradiated up to an end dose of 41.6 Gy (RT) or sham-irradiated (SR). During the last 5 days of the irradiation schedule, 5-fluorouracil (5-FU) was administered intraperitoneally in either a high dose (20 mg/kg, chemotherapy-high dose [CH]) or a low dose (10 mg/kg, chemotherapy-low dose [CL]). Animals were randomly arranged into six groups: group I, control (SR + saline intraperitoneally); group II, RT only; group III, SR + CL; group IV, RT + CL; group V, SR + CH; group VI, RT + CH. Four days after RCT, a side-to-side anastomosis was constructed between the irradiated rectosigmoid and the nonirradiated caecum. Animals were killed 10 days postoperatively. No significant differences were found in the anastomotic bursting pressure or the bursting wall tension. In group VI, mitoses were less (P < 0.01) and mucosal ulceration was more (P = 0.03) pronounced compared to group I. Sclerotic arteries were seen in all irradiated groups and in animals that received high-dose 5-FU alone. 5-FU administration in high or low dose, with or without RT, induced more inflammation in the submucosa compared to controls (P < 0.05). Conclusively, RCT has no detrimental effect on the mechanical strength of colonic anastomosis in this rat model. However, RCT with high-dose 5-FU induces more histological alterations at the anastomotic site.
El-Malt
M
M
Department of Abdominal Surgery, Ghent University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium. Mohamed.elmalt@rug.ac.be
Ceelen
W
W
van den Broecke
C
C
Cuvelier
C
C
Van Belle
S
S
De Neve
W
W
de Hemptinne
B
B
Pattyn
P
P
D000714:Anastomosis, Surgical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D003106:Colon / Q000473:pathology; D003108:Colonic Diseases / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005472:Fluorouracil / Q000627:therapeutic use*; D007249:Inflammation; D008297:Male; D008938:Mitosis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014456:Ulcer / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D014945:Wound Healing / Q000187:drug effects* / Q000528:radiation effects*
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil