Selective Cryotherapy

Abstract

Freezing tissue in situ produces a response that ranges from inflammatory to destructive. The nature of the response is related to the severity of the cryogenic injury, which is dependent upon the tissue temperature, the duration of freezing, and other factors in the freeze-thaw cycle. Therefore, by adjusting the freeze-thaw cycle to an appropriate program, the tissue response may be manipulated to achieve a selected goal. Selective cryotherapy depends on differences in the sensitivity of cells to cold injury. Most normal cells die at rather elevated freezing temperatures, but the fibrocollagenous matrix is preserved, which yields a favorable healing of the wound. Cancer cells are resistant to freezing injury and require low freezing temperatures and repeated freeze-thaw cycles. These differences permit exploration of the expanded uses of cryoablative techniques. This review focuses on the two faces of cryotherapy, that is, its destructive and preservative aspects. The efficacy of cryosurgery for tumors may be increased by adjunctive therapy, which will influence the fate of cells in an apoptotic state in the frozen volume. Tissue warming techniques can prevent destruction in unwanted areas. The current and potential use of warmer freezing temperatures features selective destruction of some cells, while avoiding injury to others, and selective functional compromise of cells with later return of function. Elevated freezing temperatures may also be used to elicit a non-destructive response to induce changes in the process of healing. These tissue responses and adjunctive therapy provide the direction for future research and therapy.