Comparison of the effects of various anticancer agents on intestinal anastomosis after intraperitoneal administration

Abstract

In this study, the effects of intraperitoneal 5-fluorouracil (5-FU), cisplatinum (Cis), adriamycin (Adr), and methotrexate (MTX) administration on rat intestinal anastomosis were compared. Cis and MTX led to significant weight loss in the first 5 days compared with the control group. Within 14 days all rats except the MTX group nearly reached their preoperative weight. No remarkable weight loss or systemic toxicity was observed among the 5-FU and Adr groups. The anastomosis bursting pressure (ABP) at 1 week was significantly lower than that of the control group (P < 0.01 and P < 0.005, respectively). On day 14 the anastomosis bursting pressure in the Cis group was similar to that of the control group but was significantly lower in the MTX group (P < 0.002). Histopathologically, MTX avoided the development of a mucosal layer at the anastomosis site and led to ulcer formation in some of the rats. The ABPs at 7 and 14 days were similar to those in the control group. Neither of the agents had any significant mechanical or histopathologic adverse effects on anastomosis. According to the results of our study, MTX impaired the healing of the anastomosis, and we thus conclude that the intraperitoneal administration of this agent is not safe. On the other hand, Cis showed a detrimental effect on the anastomosis, particularly in the early phase, but this effect disappeared in the late phase. Cis thus should not be administered in the early postoperative phase. As a result, 5-FU and Adr were found to be the safest agents as they did not delay wound healing and did not reduce the anastomotic strength.

Effects of oxaliplatin and 5-fluorouracil on the healing of colon anastomoses

“…Arikan et al reported the detrimental effects of cisplatinum on intestinal anastomoses in a model similar to ours. 32 Thus, we must examine the differences between cisplatinum and its analogue OX carefully. Shirafuji et al suggested that the depletion of macrophages in the anastomotic site is a major cause of impaired wound healing in bronchial anastomosis.…”

Optimal Timing for Surgery After Adriamycin Treatment in Rats

“…Many patients on active chemotherapy are subjected to major surgery even though chemotherapy impairs wound healing. 4,5,7,[11][12][13] Adriamycin is a broadspectrum anthracycline group chemotherapeutic agent widely used in cancer treatment. 14,15 However, it has many side effects; most notably, it is cardiotoxic, it can cause congestive cardiac insufficiency, it has a doserelated myelosuppressive effect, and it is locally toxic to the tissues, causing ulceration and necrosis if it extravasates out of vessels.…”

“…The deleterious effects of this drug are well documented and although the mechanism of impaired wound healing is understood, the exact interval of this impairment is uncertain. [2][3][4][5][6][7] The observation times in previous studies were short and different periods of wound healing were evaluated. Therefore, we evaluated the effect of adriamycin on wound healing in the long term when surgery was performed at different time points during this period, to determine the optimal timing for surgery after adriamycin treatment.…”