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Histologic evaluation of intestinal wound healing with and without cytostatics was performed in 36 rats. Variables were the relative position of the wound edges in mucosa and muscularis, necrosis, exudate, granulation tissue, granulocytes, macrophages, fibroblasts, restoration of the mucosal epithelium, and repair of the muscularis propria. The relative position of the wound edges in the mucosa and the muscularis in the initial phase of wound healing depended on technique but appeared to improve in the later phases of wound healing. It was not affected by the administration of antineoplastic agents; neither were muscularis repair, epithelial restoration of the mucosa, necrosis, nor exudate. Granulation tissue, fibroblasts and macrophages were present in maximal amounts after 7 days appearing later or showing this maximum at a different moment in time when antineoplastic agents were given. The processes of epithelial and muscularis repair were not influenced by the relative position of the wound edges. Granulation tissue, macrophages, and fibroblasts were the best parameters for measuring the histologic evolution of intestinal wound healing, and the effects of antineoplastic agents upon it.

The effects of parenteral nutrition on the healing of experimental ileal and colonic anastomoses constructed on the 3rd day of a 5-day cytostatics course were investigated. Intravenous saline alone already reduced weight loss induced by cytostatics while parenteral nutrition almost completely prevented postoperative loss of weight. A negative effect of cytostatics on anastomotic bursting strength was found in the ileum 7 days after operation. Parenteral feeding negated this effect but had no positive effect on anastomotic hydroxyproline content. Thus, parenteral nutrition increases the strength of intestinal anastomoses, constructed during a cytostatics regimen, but intravenous saline alone also appears to have a similar effect.

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.

The effect of a combination of antineoplastic agents (bleomycin (2 mg/kg/d), 5-fluorouracil (10 mg/kg/d) and cisdiamminedichloroplatinum (0.35 mg/kg/d)), given intravenously, on the healing of colonic anastomoses was investigated in rats. Ninety-six male Wistar rats were divided into four groups. A control group of rats underwent surgery only. The remaining rats were operated either 2 days before, 2 days after or during the 5-day chemotherapy course. In all groups rats were killed after 3, 7 and 21 days. Wound healing of the anastomosis was assessed by measuring the bursting pressures and hydroxyproline contents. Operating in the middle of the 5-day chemotherapy course had the greatest effect on anastomotic healing. This was most apparent on the seventh day postoperatively. When surgery was performed on the second day after the chemotherapy course there was an early delay in wound healing as measured by hydroxyproline content. Seven days postoperatively concentrations were in the same range as those in the control group. Chemotherapy commencing 2 days after surgery did not affect anastomotic healing as compared to the control group. Bursting pressure and hydroxyproline content at the end of the experiment were more or less comparable in all groups.

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.