Experimental colonic healing in relation to timing of 5-fluorouracil therapy

Abstract

In an experimental study resembling clinical use of adjuvant 5-fluorouracil (5-FU) treatment of colorectal carcinoma, 97 male Wistar rats were operated on with a standardized left colonic resection. Treatment was given as a daily intraperitoneal injection. The animals were randomized to one of four groups: early treatment with 5-FU 20 mg/kg or saline 0.1 mol/l from the day of operation to day 7 after operation, and delayed treatment with 5-FU 20 mg/kg or saline 0.1 mol/l from the third day after operation to the day before killing. The animals were killed in groups on day 7 or 10 after operation. In the group receiving early 5-FU treatment there was an increased rate of anastomotic complications (seven of 26) compared with none in the control or delayed 5-FU groups. The anastomotic breaking strength in animals having early 5-FU treatment (day 7, median 1.45 (range 0.20-2.95) N; day 10, median 1.80 (range 0.95-3.20) N) was significantly lower than that in controls on both day 7 (median 3.20 (range 2.50-3.80)N) and day 10 (median 3.20 (range 2.20-3.60)N). In the delayed 5-FU treatment group anastomotic breaking strength did not differ from that in controls. Colonic healing was not impaired when intraperitoneal 5-FU treatment was started on day 3 after operation, whereas immediate postoperative administration of 5-FU had a detrimental effect on wound healing.

The use of morphometric and fractal parameters to assess the effects of 5-fluorouracil, interferon and dexamethasone treatment on colonic anastomosis healing: an experimental study in rats

“…Weiber et al investigated the relation between the timing of 5-fluorouracil treatment introduction and anastomosis status. Their results showed that delayed treatment resulted in an uncomplicated healing process, whereas beginning the regime on the day of surgery was connected with detrimental effects on anastomosis status [42]. Similar observations were obtained in the studies by Kanellos et al who compared early and delayed combined treatment with 5-fluorouracil and interferon or folinic acid [43,44].…”

“…and Kanellos et al, delayed therapy cycles begun on the third and fourth days after surgery, respectively, were connected with significantly less detrimental influence on the healing process. Early treatment was introduced on the day of surgery in those studies and resulted in visible impairment of the anastomosis status [42,44]. In our study, treatment began on the second post-operative day.…”

Healing of Colonic Anastomoses after Immediate and Delayed Administration of 5-Fluorouracil plus Folinic Acid

“…These drugs are usually administered intravenously, although several studies have proved that, after intraperitoneal injection, high concentrations of 5-fluorouracil are achieved locally, e.g. in the liver [1][2][3]. It is already known that the early intraperitoneal administration of adjuvant chemotherapy destroys the cancer cells which have been disseminated during operation, and inhibits the micrometastases which can lead later to local failure, intraperitoneal dissemination, regional recurrence and hepatic metastases [1,2,[4][5][6][7][8].…”

Phase II study on early start of chemotherapy after excising primary colorectal cancer with distant metastases (Pearl Star 02)

“…Immediate i.p. 5‐FU also causes anastomotic leakage 31. Continuous 5‐FU infusions enabled the use of greater daily dosages and appeared safer than injecting a bolus of 5‐FU 32.…”