C-7: Molecular mechanisms of cell death following cryosurgery and the impact of super critical nitrogen

Abstract

The lesion formed during cryosurgery is a highly dynamic environment composed of gradients in ice composition, osmolarity, pH, and temperature that vary both spatially and temporally. Investigations into the mechanisms of cell death within this complex cryolesion have led to the classical view that cell death is transitional with freeze rupture nearest the cryoprobe, necrosis throughout the lesion, and a delayed apoptosis confined primarily to the periphery. More recent studies, however, have shown cell death to be more fluid. Apoptotic cell death has been observed not only in the periphery, but also at colder isotherms deep within a lesion, and studies with caspase inhibitors have shown the ability of cells to transition between apoptosis and necrosis. As studies continue to show the innate, multi-faceted nature of cryosurgery, a window has opened for the development of new strategies and technologies to more effectively ablate targeted tissues. The identification of the combination of physical and molecular cell death throughout the lesion has begun to drive a series of technological advancements in cryosurgical devices. This has led, in part, to the development of a novel cryosurgical device utilizing super critical nitrogen (SCN) as the cryogen. Capable of generating colder temperatures more rapidly and confined to a smaller overall volume, the SCN system represents the next generation of cryosurgical devices. This presentation will focus on the recent findings of rapid-onset cell death and the growing understanding of the cell death continuum, and how the integration of the molecular response with the technological advances of SCN are providing a next generation approach to cryosurgery. As the field of cryosurgery continues to evolve, it is critical that the impact on the biology of cells, tissues, and organs be understood through both device development and laboratory/clinical research. This is particularly significant as new technologies begin to offer clinically effective, cryoablative options for disease states beyond the reach of current cryosurgical devices.