Prevention of growth of metastases in rat liver by perioperative immunoactivation.

Major intraabdominal operations result in immunodepression. In addition, manipulation of malignant tumors may release tumor cells into the systemic and portal circulation. The additive effects of immunodepression and tumor cell release during surgical treatment for gastrointestinal cancer may increase the metastases of tumor to the liver. We, therefore, studied the inhibitory effect of immunoactivator OK-432 on the growth of the liver metastases in the perioperative period using a model in which rat ascites hepatoma AH-130 cells transplanted into the portal venous system consistently induce hepatic metastases. Forty-four male Donryu rats were assigned to a test group and a control group. The test group of 24 rats was treated with OK-432 (0.5 mg/day administered i.p.) for 7 days before tumor implantation, and the control group of 20 rats was treated with 0.2 ml of saline i.p. for the same number of days as the test group. The number of hepatic metastatic lesions at 14 days after tumor implantation amounted to 71.5 +/- 45.9 (SD) in the test group of 8 rats and 149.3 +/- 61.9 in the control group of 8 rats. The mean values of survival days after tumor implantation in the test group of 9 rats and the control group of 6 rats were 33.4 +/- 8.1 and 21.8 +/- 6.9, respectively. The values of OKT4+ in peripheral blood T-cell subsets in the test group of 7 rats and in the control group of 6 rats were 51.9 +/- 7.0 and 41.8 +/- 7.2%, respectively. These data showed significant differences between the two groups. Perioperative immunoactivation with OK-432 pretreatment reduced the incidence of liver metastases developed in rats given injections of tumor cells. We believe that the perioperative period is critical for the implantation and growth of metastases and that correction of perioperative immunodepression may favorably affect the development of metastatic disease and survival. This model may have relevance to the adjuvant treatment of human gastrointestinal cancer.