Intraperitoneal cytostatics impair healing of experimental intestinal anastomoses.
We investigated the effect of two doses of cytostatics, administered intraperitoneally during 5 consecutive days, on the healing of ileal and colonic anastomoses constructed on the third day. The cytostatics regimen consisted of a combination of 5-fluorouracil, bleomycin and cisplatin at 10, 2 and 0.35 mg kg-1d-1, respectively, or at twice higher doses. The lower dose was similar to that given intravenously in previous experiments. Rats were sacrificed 3 or 7 days after operation. No effects of cytostatics were observed after 3 days, neither on anastomotic bursting pressure nor on hydroxyproline concentration (microgram/mg dry weight) or content (microgram cm-1). Profound effects were seen at 7 days. In the high dose group, bursting pressures in both anastomoses were greatly reduced with respect to the control group. Concurrently, collagen synthesis was severely impaired, as indicated by sustained decreased hydroxyproline concentrations and content. The lower dose of cytostatics showed essentially similar effects on hydroxyproline parameters, but affected anastomotic strength less dramatically. The data indicate that, while intraperitoneal chemotherapy may show less detrimental systemic toxicity and thus allow higher doses, its application as an adjunct to gastrointestinal surgery may be limited because of its severe effects on anastomotic repair.
de Roy van Zuidewijn
D B
DB
Department of General Surgery, St. Radboud University Hospital, Nijmegen, The Netherlands.
Hendriks
T
T
Wobbes
T
T
de Boer
H H
HH
D000714:Anastomosis, Surgical; D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003106:Colon / Q000601:surgery*; D005472:Fluorouracil / Q000494:pharmacology*; D006909:Hydroxyproline / Q000032:analysis; D007082:Ileum / Q000601:surgery*; D008297:Male; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D015431:Weight Loss; D014945:Wound Healing / Q000187:drug effects*
D001761:Bleomycin; D002945:Cisplatin; D006909:Hydroxyproline; D005472:Fluorouracil