Abstract
BackgroundCryoablation is one of the local therapies for hepatocellular carcinoma (HCC), but its safety and effect has not been studied in patients with Child class A or B and Barcelona Clinic Liver Cancer (BCLC) stage C HCC. Metastasis-associated in colon cancer-1 (MACC1) overexpression has been associated with poor prognosis of HCC, but its predictive value to post-cryoablation outcomes remains unknown in patients with BCLC stage C HCC.MethodsThis study assessed the safety and outcomes of cryoablation measured by time to progression (TTP) and overall survival (OS), and predictive value of MACC1 mRNA and protein overexpression in tumorous tissue to post-cryoablation outcomes in 120 advanced HCC patients with child-pugh class A or B by quantitative polymerase chain reaction and immunohistochemical staining. The potenial correlation of MACC1 and c-Met expression to tumor cell proliferation and apoptosis was also analyzed.ResultsThe cryoablation in patients with advanced unresectable HCC resulted in a median TTP and OS of 5.5 (4.2- 6.7) months and 10.5 (9.0-12.0) months, respectively and no significant complications, comparable to the historical report for RFA therapy. The MACC1 mRNA and nuclear protein expression was significantly increased in tumorous tissues in these patients than that in normal liver tissue controls. Higher expression of MACC1 mRNA and nuclear protein in tumorous tissues in these patients was associated with shorter post cryoablation median TTP and OS than that with lower MACC1 expression.ConclusionsCryoablation is a safe and effective therapeutic option for patients with advanced HCC and Child-pugh class A or B cirrhosis; and a higher intratumoral expression of MACC1 or nuclear translocation predicts poor outcomes of cryotherapy in these patients.
Highlights
Cryoablation is one of the local therapies for hepatocellular carcinoma (HCC), but its safety and effect has not been studied in patients with Child class A or B and Barcelona Clinic Liver Cancer (BCLC) stage C HCC
Osada et al and our group found that cryotherapy causes local tumor necrosis, and the adjacent tumor tissue was necrotic and shrunken in HCC patients following cryoablation, which is considered as ectopic tumor suppression [9,10]
A total of 285 cryoablations were performed in 193 tumors in 120 patients with unresectable HBV-related advanced HCC, with 1, 2 and 3 procedures in 17, 41 and 62 patients, respectively
Summary
Cryoablation is one of the local therapies for hepatocellular carcinoma (HCC), but its safety and effect has not been studied in patients with Child class A or B and Barcelona Clinic Liver Cancer (BCLC) stage C HCC. The main advantage of percutaneous cryotherapy over surgical resection is that it can be used to selectively destroy HCC tumorous tissue while sparing more non-tumoral liver tissue, and better reserve liver function [8] This is important to HCC, because the majority of these patients have cirrhosis and compromised liver function. We have recently reported that the frequency of regulatory T cells had significantly decreased in patients with HCC regression following cryoablation, but dramatically increased in patients with HCC recurrence [11]. These indicated that besides HCC ablation, cryotherapy might function as a systemic treatment by improved immunity. Randomized controlled studies are needed to compare cryoablation with other therapies, such as resection and Radiofrequency Ablation (RFA)
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