Does the administration route of leucovorin have any influence on the impairment of colonic healing caused by intraperitoneal 5-fluorouracil treatment?
Intraperitoneal chemotherapy with 5-fluorouracil (5-FU) is a new, promising alternative in adjuvant treatment of advanced colorectal cancer. Leucovorin (LV), a biomodulator of 5-FU, potentiates the antineoplastic effect of 5-FU. The aim of this study was to determine whether the administration routes of LV had any influence on the impairment of colonic healing caused by intraperitoneal 5-FU treatment. 48 male Wistar rats were subjected to left colonic resection and anastomosis, and randomized to 1 of 4 groups: control group (receiving intraperitoneal NaCl, intravenous NaCl); ipFU group (receiving intraperitoneal 5-FU, intravenous NaCl); ipFU+ivLV group (receiving intraperitoneal 5-FU, intravenous LV), and ipFU+LV group (receiving intraperitoneal 5-FU+LV, intravenous NaCl). Treatment was started after surgery and continued for 5 days with daily injections. The animals were sacrificed on the 7th day postoperatively. Anastomotic complications were more common in the ipFU, ipFU+ivLV, and ipFU+LV groups (p < 0.05) compared to the control group. The anastomotic breaking strength was significantly reduced in the ipFU, ipFU+ivLV, ipFU+LV groups (p < 0.05) than in the control group, but it did not differ between the ipFU, ipFU+ivLV, and ipFU+LV groups. The hydroxyproline content of the anastomotic segment was also significantly reduced in the ipFU, ipFU+ivLV and ipFU+LV groups (p < 0.05) compared to the control group. However, there was no difference between the anastomotic hydroxyproline content of the ipFU, ipFU+ivLV, and ipFU+LV groups. In this experiment, colonic healing was impaired after intraperitoneal 5-FU administration as judged by the higher rates of anastomotic complications, reductions in anastomotic breaking strength and hydroxyproline content; but LV administration either intravenously or intraperitoneally did not cause further deterioration in colonic healing.
Haciyanli
M
M
Department of General Surgery, Dokuz Eylul University Hospital, Izmir, Turkey. mhaciyanli@hotmail.com
Fuzun
M
M
Unek
T
T
Tokgoz
Z
Z
D000714:Anastomosis, Surgical / Q000009:adverse effects; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D001769:Blood / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology; D006909:Hydroxyproline / Q000378:metabolism; D007274:Injections, Intraperitoneal; D002955:Leucovorin / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013718:Tensile Strength; D014945:Wound Healing / Q000187:drug effects*
D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D006909:Hydroxyproline; D005472:Fluorouracil