The effect of antineoplastic agents on the healing of small intestinal anastomoses in the rat.
The influence of an intravenous 5-day combined chemotherapy with bleomycin (2 mg/kg/d), 5-fluorouracil (10 mg/kg/d) and cis-diamminedichloroplatinum (0.35 mg/kg/d) on the healing of ileal anastomoses was investigated in rats. Ninety-six male Wistar rats were used, divided into four groups. The rats in the control group had surgery without administration of cytostatic agents. The other rats were operated either 2 days after, 2 days before, or during the 5-day chemotherapy course. In each group, rats were killed after 3, 7, and 21 days. Anastomotic healing was assessed by measurement of bursting pressures and hydroxyproline levels. Intestinal healing appeared to be impaired most if the operation was performed in the middle of the antineoplastic chemotherapy course. The effects were most pronounced on the seventh postoperative day. Surgery on the second day after the chemotherapy course led to a slight and early delay in wound healing as measured by the hydroxyproline content. Seven days postoperatively, concentrations had returned to preoperative values. Surgery 2 days before chemotherapy induced only minor differences with respect to the control group. In all groups, bursting pressure and hydroxyproline content at 21 days were similar. Thus, antineoplastic agents retard but do not prevent healing of intestinal anastomoses. The effects are most pronounced when surgery is performed during chemotherapy. If possible, surgery should be performed prior to chemotherapy. Increasing the time interval between surgery and chemotherapy may decrease the delay in intestinal woundhealing.
de Roy van Zuidewijn
D B
DB
Wobbes
T
T
Hendriks
T
T
Klompmakers
A A
AA
de Boer
H M
HM
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage; D006909:Hydroxyproline / Q000378:metabolism; D007082:Ileum / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013718:Tensile Strength / Q000187:drug effects; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
D001761:Bleomycin; D002945:Cisplatin; D006909:Hydroxyproline; D005472:Fluorouracil