Cryosurgery of dunning AT-1 rat prostate tumor: Thermal, biophysical, and viability response at the cellular and tissue level

This study investigates cryodestruction of the Dunning AT-1 rat prostate tumor at the single cell, tissue slice, and in vivo levels. The thermal history around a 3-mm-diameter cyclindrical cryosurgical probe was predicted by solving the bioheat equation in a one-dimensional cylindrical geometry. At various radial positions in the iceball this thermal history was approximated by a constant cooling rate and a final steady-state temperature (or end-temperature). The predicted cooling rates and end temperatures ranged from greater than or equal to 1000 degrees C/min to 5 degrees C/min and -196 degrees C to -20 degrees C, respectively. These cooling rates and end-temperatures were then imposed on single AT-1 cells, AT-1 tissue slices in vitro and AT-1 tumors inr vivo. The single cells and tissue slices were frozen by LN(2) immersion, copper block slam-freezing, or controlled cooling on a cryomicroscope or a directional solidification stage. LN(2) immersion is lethal to AT-1 cells (presumably due to intracellular ice formation), while cooling at 5-100 degrees C/min leaves some viable cells (at end-temperatures ranging between -20 and -40 degrees C). AT-1 tumor slices show extensive intracellular ice formation due to slam cooling, extensive dehydration at 100 degrees C/min, and total dehydration at rates less than or equal to 10 degrees C/min to end temperatures below -10 degrees C. Postfreeze culture and histology of the AT-1 tissue show that extensive intracellular ice formation is lethal, while cellular dehydration and vascular engorgement leave viable cells (at and temperatures between -20 and -40 degrees C). Based solely on the single cell and in vitro a tissue damage achieved by cooling rates and end-temperatures, a sizable portion of a cryosurgically frozen tumor would. be expected to survive. However in vitro cryosurgery performed on AT-1 rumors demonstrated that the tissue was damaged throughout the cryolesion, even at the periphery where the thermal history would be expected to allow single cells and tissue slices to survive in vitro. Taken together, these results suggest that damage mechanisms other than those due to cooling rate and end-temperature mag. be responsible for the increased cellular destruction at the periphery of the iceball in vivo and that cooling rate is less important than end-temperature in determining cryosurgical damage in AT-1 tumors. Experiments are ongoing to determine if the time held at an end temperature, thawing rate, vascular response, or other mechanisms are primarily responsible for the enhanced destructive capability in vivo. (C) 1997 Academic Press.