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.

Experimental cryosurgery investigations in vivo

“…These differences can be identified in single, short freezing cycles. Experiments show that the temperatures at which the differences in cell sensitivity can be identified are in the range of 0 to −30°C [59,88]. Sebaceous glands and hair follicles were also lost in this warm freezing range, but keratinocyctes survived at −30°C.…”

The molecular basis of cryosurgery

“…Severe freezing injury destroys cells and tissues, which is the prime requirement for treating tumours, producing coagulation necrosis in the frozen tissue in the days after thawing. Some differences in the sensitivity of different types of cells exist, and these are the basis of selective cryotherapy, in which the therapeutic goal is to preserve some cells while destroying others [10]. However, cancer cells in most organs, such as the prostate gland, kidney and liver, require that techniques be used to ensure destruction.…”

“…Furthermore it might be expected that therapy directed at enhancing or promoting apoptosis would be therapeutically beneficial. The expectation is that adjunctive therapy, whether in the form of cytotoxic chemotherapy, irradiation, apoptotic promoters, or immunological potentiators, will complete the destruction of cells in the cryogenic lesion and enhance the efficacy of therapy [9,10].…”