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

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Abstract
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. A model was developed in which rat colon carcinoma cells transplanted into the portal vein consistently induce hepatic metastases by 4 wk and death within 9 wk. Additionally, perioperative treatment with levamisole was shown to significantly reduce the incidence of metastases. Maleic anhydride-divinyl ether-2 (MVE-2), a known immunostimulant, was tested to see whether it would produce similar effects. Rats pretreated with MVE-2 the day before and day of tumor implantation developed fewer metastases (34% of animals treated with MVE-2, compared with 5% of animals not treated with MVE-2 had .ltoreq. 2 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 perioperative period is apparently critical for the implantation and growth of metastases and perioperative immunostimulation may be a factor in decreasing the incidence of metastases. This model may have relevance to the adjacent treatment of human colonic cancer.
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