A Study on the Enhancement of Hematogenous Metastasis by Surgical Stress

Hideaki Watanabe, Hitoshi Okahara, Akinori Higashiyama, Masahiko Sugano, Kazuhiko Nishimura, Noburu Sakakibara

First Department of Surgery, Juntendo University, School of Medicine

To defermine the influence of surgical stress on metastasis, we counted the metastatic colonies on the surface of the lung after inoculating melanoma cells into the tail veins of mice that underwent surgery. The surgical stress increased the number of metastatic colonies. To prevent host immune suppression after surgery, BRM (OK432) was administered to the mice preoperatively. Preoperative oral administration of OK432 inhibited the enhancement of metastasis by surgical stress in the murine experiment. Clinical investigation demonstrated that Stage III and IV gastric cancer patients showed a decrease in Con A-induced lymphocyte blastogenesis, and Stage IV patients also showed a decrease in NK activity after surgery. But preoperative oral administration of OK432 inhibited these decreases. NK cells are considered to play an important role in prevention of distanat metastasis, and the enhancement of metastasis may be due to the suppression of NK activity after surgery. The study suggests that preoperative administration of BRM could inhibit the enhancement of metastasis gy maintaining the NK activity after surgery.

Key words
hematogenous metastasis, surgical stress, NK activity, BRM

Reprint requests
Hedeaki Watanabe First Department of Surgery, Juntendo University, School of Medicine
2-1-1 Hongo, Bunkyo-ku, Tokyo, 113 JAPAN

Accepted
November 15, 1995

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