PERIOPERATIVE IMMUNOMODULATION IN CANCER-SURGERY

Despite undergoing a curative resection, many patients with colorectal cancer will develop and die of metastatic disease. It has been shown clinically and experimentally that surgery causes a transient period o f immunosuppression, and it is postulated that this may encourage both the implantation of surgically disseminated tumor cells and the growt h of existing micrometastases. The present study used natural killer c ell cytotoxicity (NKCC) and tumor burden to evaluate perioperative mod ulation of immunocompetence in a murine model. We measured NKCC and tu mor burden responses to a standardized surgical stress (SSS) alone, an d to either morphine sulfate (MS) (15 mg/kg subcutaneously X 4 doses), ketorolac (a prostaglandin synthetase-prostaglandin E(2)-inhibitor) ( 2.5 mg/kg subcutaneously X 4 doses), or interleukin 2 (2,000 units int raperitoneally X 3 doses) administration with the SSS. In this model, we found that both low-dose interleukin-2 (IL-2) and ketorolac reverse d the NKCC suppression associated with surgery, whereas morphine resul ted in further depression of NKCC. In addition, IL-2 significantly dec reased tumor incidence, whereas continuous MS exposure markedly increa sed tumor burden after surgery. These data suggest that IL-2 and ketor olac may be effective agents for the restoration of perioperative immu ne competence, whereas the use of continuous morphine might have signi ficant deleterious effects.