Reduced incidence of rat colon cancer metastases by perioperative immunostimulation with maleic anhydride-divinyl ether-2 (MVE-2).

Intra-abdominal operations result in profound immunodepression during a period when tumor cells are released into the systemic and portal circulations. This combination may augment tumor metastases. The authors have developed a model in which rat colon carcinoma cells transplanted into the portal vein consistently induce hepatic metastases by four weeks, and death within nine weeks. Additionally, the authors have shown that perioperative treatment with levamisole significantly reduces the incidence of metastases. This study tested whether maleic anhydride-divinyl ether-2 (MVE-2), a known immunostimulant, would produce similar effects. Rats pretreated with MVE-2 the day before and day of tumor implantation developed fewer metastases (34 percent of animals treated with MVE-2, compared with 5 percent of animals not treated with MVE-2 had less than or equal to two liver metastases). Eighteen percent of MVE-2-treated rats developed no hepatic metastases. Comparison of median liver weights between the MVE-2-treated group and the nontreated, tumor-bearing group was significant (P = 0.03) and the MVE-2-treated animals had significantly prolonged survival (P = 0.04). The authors conclude that the perioperative period is critical for the implantation and growth of metastases and that perioperative immunostimulation may be a factor in decreasing the incidence of metastases. This model may have relevance to the adjuvant treatment of human colonic cancer.