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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.Cancer 58:62-66, 1986. HE USE OF ANTINEOPLASTIC AGENTS as adjuvantT chemotherapy following surgical treatment of malignant diseases has become increasingly important. Administration of these cytotoxic drugs in the perioperative period may improve the resectability of tumors or reduce the incidence of distant or local metastases by, for instance, killing spilled tumor cells at the time of operation. One important question, however, is whether or not they exert an adverse effect on the healing of surgical wounds. Several reports describe the effect of various antineoplastic agents on the healing of intestinal ana~tomoses.'-~ In these experiments, chemotherapy consists of either a single or sequential postoperative injections of one cytostatic agent, or single injections of a combination of drugs. In clinical practice, however, most regimens consist of From the Department of General Surgery, St. Radboud University Hospital, Nijmegen, The Netherlands.Address for reprints: DBW de Roy van Zuidewijn, MD, Department of General Surgery, St. Radboud University Hospital, P. 0. Box 9 10 I , 6500 HB Nijmegen, The Netherlands.The authors thank the staff of the Central Animal Laboratory of the Medical Faculty (head: Dr. WJI van der Gulden), for administering the intravenous injections; and Dr. Ph. van Elteren (Department of Statistical Support, IJniversity of Nijmegen), for performing the statistical analysis of the experimental data.Accepted for publication ...

Background: Whole body hyperthermia induced by radiative systems has been used in therapy of malignant diseases for more than ten years. Von Ardenne and co-workers have developed the 'systemiche Krebs-Mehrschritt-Therapic' (sKMT), a combined regime including whole body hyperthermia of 42°C, induced hyperglycaemia and relative hyperoxaemia with additional application of chemotherapy. This concept has been employed in a phase I/II clinical study for patients with metastatic colorectal carcinoma at the Virchow-Klinikum since January 1997. Methods: The sKMT concept was performed eleven times under intravenous general anaesthesia, avoiding volatile anaesthetics. Core temperatures of up to 42°C were reached stepwise by warming with infrared-A-radiation (IRATHERM 2000®). During the whole procedure blood glucose levels of 380-450 mg/dl were maintained as well as PaO 2 levels above 200 mmHg. Extensive invasive monitoring was performed in all patients including measurements with the REF-Ox-Pulmonary artery catheter with continuous measuring of mixed venous saturation (Baxter Explorer®) and invasive monitoring of arterial blood pressure. Data for calculation of hemodynamic and gas exchange parameters were collected four times, at temperatures of 37°C, 40°C, 41.8-42°C and 39°C, during measurements FiO 2 was 1.0 at all times. Fluids were given in order to keep central-venous and Wedge pressure within normal range during the whole procedure. Statistics were performed using the Wilcoxon Test. Results: Statistically significant differences were found between heart rate, cardiac index and systemic vascular resistance comparing data at 37°C and 42°C. Heart rate and cardiac index increased to a maximum at 42°C (P < 0.0001) whereas systemic vascular resistance had its minimum at 42°C (P < 0.0001). Mean arterial pressure dropped with increasing temperature, differences were not significant. Calculation of stroke volume index and ventricular volumes showed only a slight decrease in endsystolic volumes with increasing temperature, the resulting differences in right ventricular ejection fraction were marginally significant (P = 0.038) comparing 42°C to baseline. Right ventricular stroke work index as well as mean pulmonary arterial pressure increased at 42°C (P = 0.0115 and P = 0.0037), pulmonary vascular resistance only dropped little compared to systemic vascular resistance, left ventricular stroke work index even dropped with increasing temperature, though showing no significant difference. Values for mixed venous oxygen saturation did not vary during therapy, pulmonary right-left shunt showed a temperature associated increase (P = 0.0323) to a maximum at 42°C. Conclusion: Under the procedure of sKMT cardiac function in patients, who do not have any pre-existing cardiac impairment, can be maintained almost unchanged, ie with normal right and left ventricular pressure, despite an increase in right ventricular stroke work Acknowledegment: Supported by Deutsche Krebshilfe.