Does the Administration Route of Leucovorin Have Any Influence on the Impairment of Colonic Healing Caused by Intraperitoneal 5-Fluorouracil Treatment?

Abstract

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.

The effect of different temporary abdominal closure techniques on fascial wound healing and postoperative adhesions in experimental secondary peritonitis

“…Because body weight changes were similar in all study groups, it seems unlikely that differences in the nutritional status are responsible for the differences in wound healing observed in the current study. There was no statistically significant difference between the groups in terms of body weight loss, and in experimental studies it has been shown that weight loss of less than 20% of body weight did not have an effect on wound healing [33,34]. Therefore, the percentage of weight reduction in animals are not enough to describe that the malnutrition is a factor that might affect the fascial wound healing in our study.…”

The Effects of Irinotecan on the Healing of Colonic Anastomoses in Rats

“…Additional intraperitoneal injections of interferon or folic acid did neither improve nor worsen the results [3]. Haciyandli et al [22] studied the effects of intravenously or intraperitoneally administered leucovorin in conjunction with 5-FU on anastomoses. They concluded that there were no further positive or negative effects on anastomotic healing or on the impairment caused by 5-FU.…”

Effects of Combined Pulse Electromagnetic Field Stimulation Plus Glutamine on the Healing of Colonic Anastomosis in Rats

“…In the current study, we determined the hydroxyproline content in the anastomotic tissue by means of a parameter of collagen synthesis and wound healing. Between the fifth and seventh days after surgery, collagen synthesis peaks and the wound strength depends mainly on these newly formed, organized collagen fibers [23]. For this reason, the seventh postoperative day was chosen to evaluate the anastomotic wound healing in our model.…”