Advanced hepatic tissue destruction in ablative cryosurgery: potentials of intermittent freezing and selective vascular inflow occlusion

Recent studies indicate that cryosurgery represents a promising approach to treat non-resectable liver tumors. To improve parenchymal tissue destruction, a variety of modifications of the freeze-thaw procedure have been suggested, including repetitive freezing and portal-triad cross-clamping. The aim of the present study was to analyze whether intermittent freezing by application of a double freeze-thaw procedure or selective vascular inflow occlusion are more effective than a single freeze-thaw cycle to achieve complete hepatic tissue destruction. Using a porcine model, intrahepatic cryolesions were induced by freezing the hepatic tissue for a total of 15 min (n = 6, SF). Additional animals (n = 6) underwent a double freeze-thaw cycle of 7.5 min each (DF). A third group of animals (n = 6) was treated by a single 15-min freeze-thaw cycle during selective vascular inflow occlusion (VO-SF). Seven days after freezing, DF did not change the volume of the cryolesion (25.4 +/- 1.7 cm(3)) compared to SF (29.9 +/- 3.7 cm(3)), however, resulted in enhanced destruction of hepatocyte nuclear morphology (DF-score: 2.4 +/- 0.2 versus SF-score: 1.1 +/- 0.3; p < 0.05) and attenuated leukocyte infiltration within the margin of the cryolesion (DF-score: 1.5 +/- 0.2 versus SF-score: 2.8 +/- 10.1; p < 0.05). VO-SF was also effective to significantly enhance destruction of hepatocyte nuclear morphology (2.8 +/- 0.1; p < 0.05 versus SF), but, additionally, markedly increased the volume of the cryolesions (43.3 +/- 5.3 cm(3); p < 0.05 versus SF and DF). Interestingly, VO-SF further increased the number of apoptotic cells, while leukocyte infiltration (2.3 +/- 0.3) was not affected compared to that after SF-treatment. Thus, our data indicate that both DF and VO-SF are effective to enhance parenchymal cell destruction within the margin of the cryolesion. VO-SF additionally increases the volume of the lesion and may therefore be most attractive for successful clinical application. (C) 2004 Elsevier Inc. All rights reserved.