In the present article, recent research efforts in our laboratory to improve cryosurgery by use of mechanistically derived adjuvants are reviewed. Our research has been focused on enhancing two freezing induced injury mechanisms ? i) direct cell injury by use of thermophysical adjuvants, and ii) vascular injury by use of an inflammatory adjuvant. The thermophysical adjuvants are chemicals, usually salts, which can induce secondary crystallization, called eutectic solidification, in a cryolesion; thereby enhancing direct cell injury. The inflammatory adjuvant is a cytokine, tumor necrosis factor-alpha (TNF-α), which upregulates inflammation of microvasculature in tumors prior to freezing to promote vascular injury in the cryolesion. Even though the individual mechanism of injury enhancement within the cryolesion of each adjuvant requires further study, both adjuvants are envisioned to enlarge the complete killing zone so that the boundary of the cryolesion matches more closely with the edge of iceball. By bringing the edge of the cryolesion closer to the edge of iceball, the adjuvants hold promise for improvement of image guidance and outcome of cryosurgery.

Key words: Enhancement of cryoinjury, Adjuvants, Direct cell injury, Eutectic solidification, Vascular injury, Inflammation, Tumor necrosis factor - alpha.