Large volume hepatic freezing: association with significant release of the cytokines interleukin‐6 and tumor necrosis factor a in a rat model

Abstract

Although cryotherapy of liver tumors is generally considered a safe procedure, a syndrome of coagulopathy and fatal multiorgan failure has been observed in some patients and is called the cryoshock phenomenon. Our aim was to establish an animal model of this phenomenon and examine the effects of the basic parameters of freezing or cryotherapy on it. A group of 75 female Sprague-Dawley rats were allocated randomly to five groups: (1) sham laparotomy (n = 15); (2) small (25% liver volume) single freeze (n = 15); (3) small (25% liver volume) double freeze (n = 15); (4) large (50% liver volume) single freeze (n = 15); (5) large (50% liver volume) double freeze (n = 15). Blood samples were collected at different postoperative times, and organs were harvested for histopathology. There was a significant release of tumor necrosis factor-a (TNFa) and interleukin 6 (IL-6) following hepatic freezing, which was greatest in group 5. Postoperative serum cytokine levels were significantly associated with hepatocellular injury, as measured by postoperative serum aspartate transaminase (AST) concentrations. Severe hemoglobinuria and renal injury, as demonstrated by the serum creatinine level and the glomerular neutrophil count, were observed and were greatest in group 5. Hepatic cryosurgery is associated with release of IL-6 and TNFa and renal injury in a rat model. It is likely that the cryoshock phenomenon is another form of the systemic inflammatory response syndrome. Based on the results of this study, it is possibly mediated by cytokines released from the frozen liver tissue. We therefore caution against cryotherapy of large tumor volumes.

TNF-α–based accentuation in cryoinjury—dose, delivery, and response

“…Interestingly, reperfusion of large cryosurgical iceballs releases various cytokines, including TNF-a, acutely into the blood system and can be associated with ''cryoshock,'' which can lead to organ failure and death (36). This additive effect may explain the death of the animals in this study, which were systemically injected with soluble TNF-a before cryosurgery.…”

Hepatic Hemorrhage Caused by Percutaneous Tumor Ablation: Radiofrequency Ablation versus Cryoablation in a Porcine Model

“…It is also possible that the hemorrhage encountered in historic studies of cryoablation was associated with hepatic cracking due to freezing in a very large volume. While it is possible that some physicians will still treat very large tumors with ablation, reports of increased local failures and complications associated with ablation in large tumors have discouraged many physicians from routinely treating large tumors with ablation of any modality (35,36).…”

Thermal Tumor Ablation in Clinical Use

“…Yet, cryoablation is not indicated for some types of cancer. Cryoablation does not provide a cautery effect, so the rapid introduction of cellular contents into the bloodstream after thawing can lead to a dangerous response known as cryoshock [43]. A similar effect can be noted with neuroendocrine tumors.…”