CPT-11 converting carboxylesterase and topoisomerase activities in tumour and normal colon and liver tissues.

CPT-11 is a prodrug activated by carboxylesterases to the active metabolite SN-38 which is a potent inhibitor of topoisomerase I. CPT-11 is of clinical interest in the treatment of colorectal cancer. We evaluated the activities of CPT-11 converting carboxylesterase (CPT-CE) and topoisomerase I (topo I) in 53 colorectal tumours, in eight liver metastases and in normal tissue adjacent to the tumours. Both CPT-CE and topo I activities were widely variable in the malignant and the normal tissue of patients with colorectal carcinomas. CPT-CE was only two to threefold lower in primary tumours compared to normal liver, suggesting that a local conversion to SN-38 might occur in tumour cells. CPT-CE was similar in liver and in normal colon tissues. Levels of topo I in tumour ranged from 580 to 84 900 U mg protein(-1) and was above 40 000 U mg protein(-1) in 11 of 53 patients. Similarly, a very high ratio (> 5) between tumour and normal tissues were observed in 12 of 53 patients. An inverse correlation was observed between the topo I activity and the clinical stage of disease. Clinical studies are in progress in our institution to explore a possible relationship between CPT-CE and topo I activities in tumour cells and the response to CPT-11-based chemotherapy in patients with colorectal cancer.

[Evaluation of systemic antibiotic preventive treatment in colorectal surgery]. / Appréciation de l'antibio-prophylaxie systémique en chirurgie colo-rectale.

A comparison was made of two methods of prophylactic antibiotic therapy against the septic complications of colonic and rectal surgery: --preoperative oral antibiotics associated with peroperative systemic antibiotics; --peroperative systemic antibiotics only, continued for 24 hours after surgery. Both types of antibiotic therapy were of short duration and were designed to cover aerobic and anaerobic organisms. Two groups of 30 patients were selected at random. They were homogeneous. The septic complication rate was 10% in the oral plus systemic and 24% in the systemic group. It is felt that the combination of oral and systemic antibiotics remains preferable, in particular bearing in mind the efficacy of oral metronidazole.

Comparison between oral and systemic antibiotics and their combined use for the prevention of complications in colorectal surgery.

Ninety patients were included in this prospective randomized trial. Each required electric colorectal surgery and was prepared for operation with oral preoperative antibiotic therapy, systemic peroperative therapy, or by a combination of both. The number of each type of septic postoperative complication and their total did not differ between the group treated by oral antibiotics prior to operation and the group treated peroperatively with systemic antibiotic therapy. The total number of septic complications (wall abscesses, fistulas, subdiaphragmatic abscesses, septicemia, peritonitis), however, was significantly less (P less than 0.05) in the group treated by both preoperative oral antibiotics and peroperative systemic antibiotic therapy (3.3 per cent) than in either groups treated only orally preoperatively (30 per cent) or by systemic antibiotic therapy during the operation (23 per cent). The combination of oral antibiotic therapy prior to operation and of systemic peroperative antibiotic therapy, therefore, presents the most effective prophylactic effectiveness.