Pre-treatment inflammation induced by TNF-α augments cryosurgical injury on human prostate cancer

Vascular injury is a major mechanism of cryosurgical destruction. The extent of vascular injury may be affected by the addition of molecular adjuvants. This study, in addition to determining the injury mechanism in the LNCaP Pro 5 human prostate cancer subline grown in a nude mouse, examined the effect of cytokine TNF-α on cryosurgery of an in vivo microvascular preparation (Dorsal Skin Flap Chamber). A comparison of injury data to a thermal model indicated that the minimum temperature after moderate cooling, thawing, and hold time required for causing necrosis was 3.5±6.9°C in TNF-α-treated LNCaP Pro 5 tumor tissue (n=4) and -9.8±5.8°C in TNF-α-treated normal skin of the nude mouse (n=4). Compared to tissues without TNF-α treatment, where the minimum temperature required for causing necrosis was -16.5±4.3°C in LNCaP Pro 5 tumor tissue (n=8) and -24.4±7.0°C in normal skin of the nude mouse (n=9), the results indicate the local use of TNF-α can dramatically increase the threshold temperature of cryo-destruction by more than 10°C (p<0.01). These findings were consistent with the hypothesis that vascular-mediated injury is responsible for defining the edge of the cryolesion in microvascular-perfused tissue, and therefore pre-induced inflammation can augment cryoinjury. The local use of TNF-α to pre-inflame prostate cancer promises to increase both the ability of freezing to destroy cancer as well as improve the ability of ultrasound or other iceball-monitoring techniques to predict the outcome of the treatment.