Preoperative insulin reverses cachexia and decreases mortality in tumor-bearing rats

Abstract

As a model of surgical stress in the cancer-bearing animal, we resected large flank sarcomas from cachectic rats under ether anesthesia and closed wounds primarily. The metabolic cost of tumor resection was measured using a long-term continuous indirect calorimeter. In the immediate postresection period energy balance decreased and host energy expenditure increased significantly ( P < 0.005). In animals with similar tumor weights, mortality following resection was determined by the degree of cachectic depletion. We then considered whether improvement of preoperative host nutritional status with insulin treatment might improve a subsequent surgical outcome. Insulin, when administered exogenously to cachectic tumor-bearing rats, has been shown to stimulate food intake and preserve host weight and does not stimulate tumor growth. When individual rats bearing a cachexia-producing flank sarcoma demonstrated a decline in food intake to <75% of predicted (approximately 25 days after tumor implantation), they were randomized to receive either daily injections of NPH insulin (2 units/100 g/day) for 5 days or no treatment for 5 days. Animals then underwent tumor resection and 14-day survival was measured. All resections were performed in an unbiased manner without the surgeon's knowledge of each rat's treatment status. In an experiment using 59 rats, insulin-treated rats had a threefold higher 5-day preoperative food intake and did not lose weight in the preoperative period, while untreated rats lost 17 g ( P < 0.001). Mortality in the insulin-treated group was 10% versus 28% in the untreated group. The experiment was repeated using 50 rats with deeper, more locally invasive tumors with similar results. Operative mortality was 20% in the insulin treated group versus 60% in the untreated group ( P < 0.001, χ 2 test). Preoperative insulin therapy of cachectic TB rats appeared to reverse host cachexia and improve survival following tumor resection.