Hepatic cryoablation, but not radiofrequency ablation, results in lung inflammation

Objective To compare the effects of 35% hepatic cryoablation with a similar degree of radiofrequency ablation (RFA) on lung inflammation, nuclear factor kappa B (NF-kappa B) activation, and production of NF-kappa B dependent cytokines. Summary Background Data Multisystem injury, including acute lung injury, is a severe complication a ssociated with hepatic cryoablation of 30% to 35% or more of liver parenchy ma, but this complication has not been reported with RFA. Methods Sprague-Dawley rats underwent 35% hepatic cryoablation or RFA and were kill ed at 1, 2, and 6 hours. Liver and lung tissue were freeze-clamped for meas urement of NF-kappa B activation, which was detected by electrophoretic mob ility shift assay. Serum concentrations of tumor necrosis factor alpha and macrophage inflammatory protein 2 were measured by enzyme-linked immunosorb ent assay. Histologic studies of pulmonary tissue and electron microscopy o f ablated liver tissue were compared among treatment groups, Results Histologic lung sections after cryoablation showed multiple foci of periven ular inflammation, with activated lymphocytes, foamy macrophages, and neutr ophils. In animals undergoing RFA, inflammatory foci were not present. NF-k appa B activation was detected at 1 hour in both liver and lung tissue samp les of animals undergoing cryoablation but not after RFA, and serum cytokin e levels were significantly elevated in cryoablation versus RFA animals. El ectron microscopy of cryoablation-treated liver tissue demonstrated disrupt ion of the hepatocyte plasma membrane with extension of intact hepatocyte o rganelles into the space of Disse; RFA-treated liver tissue demonstrated co agulative destruction of hepatocyte organelles within an intact plasma memb rane. To determine the stimulus for systemic inflammation, rats treated wit h cryoablation had either immediate resection of the ablated segment or del ayed resection after a 15-minute thawing interval. Immediate resection of t he cryoablated liver tissue prevented NF-kappa B activation and lung injury ; however, pulmonary inflammatory changes were present when as little as a 15-minute thaw interval preceded hepatic resection, Conclusions Hepatic cryoablation, but not RFA, induces NF-kappa B activation in the non ablated liver and lung and is associated with acute lung injury. Lung infla mmation is associated with the thawing phase of cryoablation and may be rel ated to soluble mediator(s) released from the cryoablated tissue. These fin dings correlate the clinical observation of an increased incidence of multi system injury. including adult respiratory distress syndrome (ARDS), after cryoablation but not RFA.