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 kappaB (NF-kappaB) activation, and production of NF-kappaB dependent cytokines.


BACKGROUND
Multisystem injury, including acute lung injury, is a severe complication associated with hepatic cryoablation of 30% to 35% or more of liver parenchyma, but this complication has not been reported with RFA.


METHODS
Sprague-Dawley rats underwent 35% hepatic cryoablation or RFA and were killed at 1, 2, and 6 hours. Liver and lung tissue were freeze-clamped for measurement of NF-kappaB activation, which was detected by electrophoretic mobility shift assay. Serum concentrations of tumor necrosis factor alpha and macrophage inflammatory protein 2 were measured by enzyme-linked immunosorbent assay. Histologic studies of pulmonary tissue and electron microscopy of ablated liver tissue were compared among treatment groups.


RESULTS
Histologic lung sections after cryoablation showed multiple foci of perivenular inflammation, with activated lymphocytes, foamy macrophages, and neutrophils. In animals undergoing RFA, inflammatory foci were not present. NF-kappaB activation was detected at 1 hour in both liver and lung tissue samples of animals undergoing cryoablation but not after RFA, and serum cytokine levels were significantly elevated in cryoablation versus RFA animals. Electron microscopy of cryoablation-treated liver tissue demonstrated disruption of the hepatocyte plasma membrane with extension of intact hepatocyte organelles into the space of Disse; RFA-treated liver tissue demonstrated coagulative destruction of hepatocyte organelles within an intact plasma membrane. To determine the stimulus for systemic inflammation, rats treated with cryoablation had either immediate resection of the ablated segment or delayed resection after a 15-minute thawing interval. Immediate resection of the cryoablated liver tissue prevented NF-kappaB 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-kappaB activation in the nonablated liver and lung and is associated with acute lung injury. Lung inflammation is associated with the thawing phase of cryoablation and may be related to soluble mediator(s) released from the cryoablated tissue. These findings correlate the clinical observation of an increased incidence of multisystem injury, including adult respiratory distress syndrome (ARDS), after cryoablation but not RFA.
Chapman
W C
WC
Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN, USA. will.chapman@surgery.mc.vanderbilt.edu
Debelak
J P
JP
Wright Pinson
C
C
Washington
M K
MK
Atkinson
J B
JB
Venkatakrishnan
A
A
Blackwell
T S
TS
Christman
J W
JW
D000818:Animals; D017115:Catheter Ablation; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000097:blood; D003452:Cryosurgery; D004797:Enzyme-Linked Immunosorbent Assay; D008099:Liver / Q000473:pathology / Q000601:surgery*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008854:Microscopy, Electron; D015846:Monokines / Q000097:blood; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D015846:Monokines; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha