Enhancement of experimental pulmonary metastasis and inhibition of subcutaneously transplanted tumor growth following cryosurgery

We have previously reported that inhibition of antitumor immune responses a nd a corresponding enhancement of metastatic tumor growth occurred in rats following cryosurgery of 3-methylcholanthrene-induced WKA rat fibrosarcoma (KMT-17). In this study, to evaluate the enhancement of metastasis arising from the inhibition of anti-tumor immune responses following cryosurgery, w e examined how cryosurgery affected experimental pulmonary metastasis and t he growth of subcutaneously transplanted tumor. To reveal the effect of cry osurgery on pulmonary metastasis, rats received subcutaneous inoculation of KMT-17 turner in the light flank (1x10(6)) and Lv. injection (1x10(5)) on the same day or 4 days later. The right flank tumors were treated with cryo surgery 5 days after subcutaneous transplantation. The pulmonary metastasis of the rats, which were injected i.v. one day before treatment, was enhanc ed by cryosurgery as compared with surgical excision, though the pulmonary metastasis of rats, which were injected i.v. 5 days before treatment, was u n-affected by cryosurgery. These observations suggest that cryosurgery may enhance the pulmonary metastasis in its early steps but has no effects in i ts later stages. To reveal the effect of cryosurgery on the growth of dista nt tumors, rats received subcutaneous inoculations of KMT-17 tumor in the r ight (1x10(6)) and left (1x10(4)similar to 10(5)) flanks. Tumors in the rig ht flank Here treated with cryosurgery 5 days after inoculation and the gro wth of untreated left flank tumors was observed. In this double grafted tum or system however, cryosurgery significantly inhibited the growth of the un ttreared left flank tumors. Spleen cells obtained from rats which had under gone cryosurgery 4 or 10 days previously (cryo-spleen, cells) were used for in vivo neutralizing Winn assay. Antitumor activity of cryo-spleen cells w as decreased as compared with that of rats after surgical excision in both spleen cells from 4 and 10 days after treatment. These findings suggest tha t effector cells in the spleen may not participate in subcutaneous tumor re gression and that the evaluation of antitumor effect using the double graft ed tumor system needs caution.