USEFULNESS OF METYRAPONE TREATMENT TO SUPPRESS CANCER METASTASIS FACILITATED BY SURGICAL STRESS

Background. One causative factor of tumor metastasis enhanced by surgi cal stress is thought to be hypersecretion of endogenous glucocorticoi ds. This study evaluated the effectiveness of metyrapone treatment and adrenalectomy in preventing the harmful effects of glucocorticoids in the enhancement of tumor metastasis resulting from surgical stress. M ethods. the effect of dexamethasone on pulmonary metastasis of MRMT-1 cells and on the number of peripheral lymphocytes was evaluated in rat s. To evaluate the suppressive effect of adrenalectomy and metyrapone treatment on operation-induced enhancement of metastasis, several para meters such as induction of pulmonary metastasis, serum corticosterone levels, and the number of blood lymphocytes and apoptotic thymocytes were determined. Results. With dexamethasone treatment, the number of peripheral lymphocytes rapidly decreased; in contrast, pulmonary metas tasis increased. The serum corticosterone level was doubled at 1 hour, apoptotic thymocyte numbers were increased about sevenfold at 3 hours and about fourfold at 6 hours, and blood lymphocyte numbers were decr eased at 3 hours after laparotomy, which facilitated about a 10-fold i ncrease in the pulmonary metastasis. These changes were almost complet ely suppressed by preoperative adrenalectomy and metyrapone treatment. Conclusions. Preoperative metyrapone treatment, which suppresses hype rsecretion of endogenous glucocorticoids as a result of operation, mod ulates the enhancement of cancer metastases and may be an effective tr eatment.