Application of high-intensity focused ultrasound ablation to patients with hepatocellular carcinoma and cirrhosis

Abstract

Despite the advancement of operative techniques and experience gained in complicated hepatectomy, the treatment of hepatocellular carcinoma (HCC) in patients with cirrhosis remains difficult. Local ablative treatment provides a chance of cure for patients with HCCs unresectable due to poor liver function. Radiofrequency ablation (RFA) and high-intensity focused ultrasound (HIFU) ablation are two modes of local ablative treatment. The former has been widely used while the latter is a relatively new option. The aim of this thesis is to investigate the safety profile of the latter and its role in the treatment of HCC in patients with cirrhosis.

From 2001 to 2007, 310 patients underwent RFA as a treatment for HCC. Evaluation of the safety profile of this treatment option found that complications of RFA occurred in 39 patients. Multivariate analysis revealed an association between intolerance of RFA and cirrhosis. RFA may not be well tolerated in patients with marginal liver function.

Since RFA had been found not well tolerated in patients with cirrhosis, the safety profile of HIFU ablation was examined. From October 2008 to June 2010, 100 patients underwent HIFU ablation for HCC. Thirteen patients showed intolerance of the treatment, which was mainly manifested as skin or subcutaneous injury. HIFU ablation was well tolerated in patients with cirrhosis.

The efficacy of HIFU treatment was further evaluated. Forty-seven patients with HCCs <3 cm received HIFU treatment between October 2006 and September 2010. Fifty-nine patients who underwent percutaneous RFA were selected for comparison. More patients (34% vs. 8.5%) in the HIFU group had Child-Pugh B cirrhosis. Patients with complete tumor ablation in the two groups had comparable survival at 1 year and 3 years.

The efficacy of HIFU ablation in treating larger HCCs was evaluated. Twenty-six patients with HCCs measuring 3-8 cm underwent HIFU treatment between October 2003 and September 2010. Fifty-two patients with matched tumor characteristics who received transarterial chemoembolization (TACE) as the primary treatment were selected for comparison. In the HIFU group, the rates of complete response, partial response, stable disease and progressive disease were 50%, 7.7%, 25.6% and 7.7% respectively. In the TACE group, the corresponding rates were 0%, 21.2%, 63.5% and 15.4%. Patients in the HIFU group had longer survival (29.8 vs. 17.6 months).

In 2006, HIFU ablation was successfully performed on a liver transplant candidate who had HCC. With the successful results gained in this case, HIFU therapy was given to other liver transplant candidates with HCC. From January 2007 to December 2010, 49 consecutive patients who had HCC within the UCSF criteria were listed for liver transplantation. The median waiting time for transplantation was 9.5 months. Fifteen patients received no treatment before transplantation. Five patients received HIFU ablation and 29 patients received TACE as a bridging therapy. Another 5 patients who had HCC within the UCSF criteria but were not listed for transplantation also received HIFU ablation and were also included in the study. In the HIFU group, 9 patients had complete response and 1 patient had partial response to the treatment. In the TACE group, only 1 patient had response to the treatment while 14 patients had stable disease and 14 patients had progressive disease. Seven patients in the TACE group but none in the HIFU group dropped out of the transplant waiting list.

In conclusion, HIFU is effective in treating patients with small HCCs and selected patients with larger HCCs. It is safe even for patients with cirrhosis. As patients with cirrhosis tolerate HIFU treatment well, it is a suitable bridging therapy for liver transplant candidates.