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 prosta te tumor at the single cell, tissue slice, and in vivo levels. The the rmal history around a 3-mm-diameter cyclindrical cryosurgical probe wa s predicted by solving the bioheat equation in a one-dimensional cylin drical geometry. At various radial positions in the iceball this therm al history was approximated by a constant cooling rate and a final ste ady-state temperature (or end-temperature). The predicted cooling rate s and end temperatures ranged from greater than or equal to 1000 degre es C/min to 5 degrees C/min and -196 degrees C to -20 degrees C, respe ctively. 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 vi vo. 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 A T-1 cells (presumably due to intracellular ice formation), while cooli ng at 5-100 degrees C/min leaves some viable cells (at end-temperature s ranging between -20 and -40 degrees C). AT-1 tumor slices show exten sive intracellular ice formation due to slam cooling, extensive dehydr ation at 100 degrees C/min, and total dehydration at rates less than o r equal to 10 degrees C/min to end temperatures below -10 degrees C. P ostfreeze 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 sizab le portion of a cryosurgically frozen tumor would. be expected to surv ive. However in vitro cryosurgery performed on AT-1 rumors demonstrate d that the tissue was damaged throughout the cryolesion, even at the p eriphery where the thermal history would be expected to allow single c ells and tissue slices to survive in vitro. Taken together, these resu lts suggest that damage mechanisms other than those due to cooling rat e and end-temperature mag. be responsible for the increased cellular d estruction at the periphery of the iceball in vivo and that cooling ra te is less important than end-temperature in determining cryosurgical damage in AT-1 tumors. Experiments are ongoing to determine if the tim e held at an end temperature, thawing rate, vascular response, or othe r mechanisms are primarily responsible for the enhanced destructive ca pability in vivo. (C) 1997 Academic Press.