Purpose

To assess usefulness of adding contrast-enhanced ultrasonography (CEUS) to fusion imaging (FI) for percutaneous radiofrequency ablation (RFA) of hepatocellular carcinomas (HCCs) inconspicuous on FI alone. Therapeutic outcomes of RFA under CEUS-added FI guidance for HCCs inconspicuous on FI alone were also evaluated.

Methods

This prospective study was approved by the institutional review board and informed consent was obtained from all patients. Planning US was performed with FI for 126 patients with a single HCC (1-2 cm) to evaluate the feasibility of RFA by grading lesion conspicuity score using a four-point scale. RFA was performed under CEUS-added FI guidance for HCCs inconspicuous on FI alone. We evaluated how many HCCs initially inconspicuous on FI became conspicuous after adding CEUS. After CEUS-added FI-guided RFA, therapeutic outcomes including rates of technical success, primary technique efficacy, major complications, and local tumor progression were assessed.

Results

After adding CEUS, 90.5% (19/21) of all tumors initially inconspicuous on FI became conspicuous, thus enabling direct targeting for RFA. Technical success and primary technique efficacy rates were 94.7% (18/19) and 100% (19/19), respectively. No major complications were observed after RFA. Cumulative local tumor progression rates after RFA were estimated to be 5.3%, 10.8%, and 10.8% at 1, 2, and 3 years, respectively.

Conclusion

Adding CEUS to FI is useful for improving the conspicuity of HCCs inconspicuous on FI alone, thus enabling successful percutaneous RFA with excellent therapeutic outcomes.

Fibrosis and cancer represent two major complications of chronic liver disease. MicroRNAs have been implicated in the development of fibrosis and cancer, thus constituting potential therapeutic targets. Here, we investigated the role of microRNA-21 (miR-21), a microRNA that has been implicated in the development of fibrosis in multiple organs and has also been suggested to act as an "oncomir." Accordingly, miR-21 was the microRNA that showed the strongest up-regulation in activated hepatic stellate cells (HSCs) in multiple models of fibrogenesis, with an 8-fold to 24-fold induction compared to quiescent HSCs. However, miR-21 antisense inhibition did not suppress the activation of murine or human HSCs in culture or in liver slices. Moreover, genetic deletion of miR-21 in two independently generated knockout mice or miR-21 antisense inhibition did not alter HSC activation or liver fibrosis in models of toxic and biliary liver injury. Despite a strong up-regulation of miR-21 in injury-associated hepatocellular carcinoma and in cholangiocarcinoma, miR-21 deletion or antisense inhibition did not reduce the development of liver tumors. As inhibition of the most up-regulated microRNA did not affect HSC activation, liver fibrosis, or fibrosis-associated liver cancer, we additionally tested the role of microRNAs in HSCs by HSC-specific Dicer deletion. Although Dicer deletion decreased microRNA expression in HSCs and altered the expression of select genes, it only exerted negligible effects on HSC activation and liver fibrosis.

Conclusion

Genetic and pharmacologic manipulation of miR-21 does not inhibit the development of liver fibrosis and liver cancer. Moreover, suppression of microRNA synthesis does not significantly affect HSC phenotype and activation. (Hepatology 2018;67:2414-2429).