title: Advanced hepatic tissue destruction in ablative cryosurgery: potentials of intermittent freezing and selective vascular inflow occlusion.
abstract: 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+/-0.1; 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.
authors.affiliation: Department of General, Visceral and Vascular Surgery, D-66421 Homburg/Saar, Germany. chokol@uniklinik-saarland.de
authors.forename: Otto
authors.initials: O
authors.lastname: Kollmar
authors.forename: Sven
authors.initials: S
authors.lastname: Richter
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schilling
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Georg A
authors.initials: GA
authors.lastname: Pistorius
mesh_terms: D000818:Animals; D003452:Cryosurgery / Q000379:methods*; D005260:Female; D005615:Freezing; D006498:Hepatectomy; D008099:Liver / Q000098:blood supply* / Q000473:pathology / Q000601:surgery*; D008102:Liver Circulation; D008297:Male; D013552:Swine