Advanced hepatocellular carcinoma: treatment with high-intensity focused ultrasound ablation combined with transcatheter arterial embolization.

PURPOSE To evaluate ultrasonographically (US)-guided high-intensity focused ultrasound ablation combined with transcatheter arterial chemoembolization (TACE) in the treatment of stage IVA hepatocellular carcinoma (HCC). MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. From November 1998 to May 2000, 50 consecutive patients with stage IVA HCC (TNM classification, T4N0-1M0) were alternately enrolled in one of two treatment groups: group 1 (n = 26), in which TACE was performed alone, and group 2 (n = 24), in which transcutaneous ablation of HCC with high-intensity focused ultrasound was performed 2-4 weeks after TACE. The tumors were 4-14 cm in diameter (mean, 10.5 cm). Immediate therapeutic effects were assessed at follow-up with Doppler US and computed tomography or magnetic resonance imaging. All patients were followed up for 3-24 months (mean, 8 months) to observe long-term therapeutic effects and complications in both groups. Tumor reduction rates, median survival time, and cumulative survival rates in both groups were calculated by using the unpaired Student t test and Kaplan-Meier method. RESULTS No severe complication was observed after focused ultrasound ablation, and no unexpected side effects were noted after TACE. Follow-up images showed absence or reduction of blood supply in the lesions after focused ultrasound ablation when compared with blood supply after TACE alone. The median survival time was 11.3 months in group 2 and 4.0 months in group 1 (P = .004). The 6-month survival rate was 80.4%-85.4% in group 2 and 13.2% in group 1 (P = .002), and the 1-year survival rate was 42.9% and 0%, respectively. Median reductions in tumor size as a percentage of initial tumor volume at 1, 3, 6, and 12 months after treatment, respectively, were 28.6%, 35.0%, 50.0%, and 50.0% in group 2 and 4.8%, 7.7%, 10.0%, and 0% in group 1 (P < .01). CONCLUSION The combination of high-intensity focused ultrasound ablation and TACE is a promising approach in patients with advanced-stage HCC, but large-scale randomized clinical trials are necessary for confirmation.

[1]  D. Gianfelice,et al.  MR imaging-guided focused US ablation of breast cancer: histopathologic assessment of effectiveness-- initial experience. , 2003, Radiology.

[2]  A. Roche,et al.  A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma. , 1990, Journal of hepatology.

[3]  J. McGahan,et al.  Radiofrequency ablation of the liver: current status. , 2001, AJR. American journal of roentgenology.

[4]  D J Collins,et al.  MRI study of hepatic tumours following high intensity focused ultrasound surgery. , 1997, The British journal of radiology.

[5]  T. Livraghi,et al.  Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection. , 1995, Radiology.

[6]  M. Makuuchi,et al.  Results of surgical and nonsurgical treatment for small‐sized hepatocellular carcinomas: A retrospective and nationwide survey in Japan , 2000, Hepatology.

[7]  K Hynynen,et al.  In vivo demonstration of noninvasive thermal surgery of the liver and kidney using an ultrasonic phased array. , 1999, Ultrasound in medicine & biology.

[8]  T. Ponchon,et al.  Extracorporeal ablation of liver tissue by high-intensity focused ultrasound. , 1993, Oncology.

[9]  W R Lees,et al.  Minimally invasive treatment of malignant hepatic tumors: at the threshold of a major breakthrough. , 2000, Radiographics : a review publication of the Radiological Society of North America, Inc.

[10]  T. Lin,et al.  Role of surgery in the treatment of primary carcinoma of the liver: A 31‐year experience , 1987, The British journal of surgery.

[11]  Y. I. Kim,et al.  Therapeutic effect of transcatheter oily chemoembolization therapy for encapsulated nodular hepatocellular carcinoma: CT and pathologic findings. , 1992, Radiology.

[12]  Y. Jan,et al.  Hepatic resection in 120 patients with hepatocellular carcinoma. , 1989, Archives of surgery.

[13]  J. Bruix,et al.  Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. , 1996, Gastroenterology.

[14]  P. Brissot,et al.  [Non surgical treatment of hepatocellular carcinoma]. , 1992, La Revue du praticien.

[15]  Claudio M Pacella,et al.  Hepatocellular carcinoma: long-term results of combined treatment with laser thermal ablation and transcatheter arterial chemoembolization. , 2001, Radiology.

[16]  H. Hasegawa,et al.  Natural history of hepatocellular carcinoma and prognosis in relation to treatment study of 850 patients , 1985, Cancer.

[17]  M. Makuuchi,et al.  Hepatocellular carcinoma: treatment with intraarterial iodized oil with and without chemotherapeutic agents. , 1987, Radiology.

[18]  Xin-da Zhou,et al.  Experience with liver resection after hepatic arterial chemoembolization for hepatocellular carcinoma , 1993, Cancer.

[19]  J. Okamura,et al.  Transcatheter chemo‐embolization effective for treating hepatocellular carcinoma. A histopathologic study , 1984, Cancer.

[20]  M. Rinaldi,et al.  Unresectable hepatocellular carcinoma in cirrhosis: survival, prognostic factors, and unexpected side effects after transcatheter arterial chemoembolization. , 1996, Digestive diseases and sciences.

[21]  Wen-zhi Chen,et al.  Tumor vessel destruction resulting from high-intensity focused ultrasound in patients with solid malignancies. , 2002, Ultrasound in medicine & biology.

[22]  Z. Wang,et al.  Targeted damage effects of high intensity focused ultrasound (HIFU) on liver tissues of Guizhou Province miniswine. , 1997, Ultrasonics sonochemistry.

[23]  T. Uto,et al.  MR Imaging of the Liver before and after Transcatheter Hepatic Chemo-Embolization for Hepatocellular Carcinoma , 1990, Acta radiologica.

[24]  R. Holcombe,et al.  Surgical and nonsurgical management of primary and metastatic liver tumors. , 1998, The American surgeon.

[25]  J. Chapelon,et al.  Extracorporeal high‐intensity focused ultrasound for VX2 liver tumors in the rabbit , 1995, Hepatology.

[26]  F. Wu,et al.  [Pathological study of extracorporeally ablated hepatocellular carcinoma with high-intensity focused ultrasound]. , 2001, Zhonghua zhong liu za zhi [Chinese journal of oncology].

[27]  F. Fry,et al.  High-intensity focused ultrasound in the treatment of experimental liver cancer. , 1991, Archives of surgery.

[28]  Gail ter Haar,et al.  High intensity ultrasound. , 2001 .

[29]  P. Johnson,et al.  Systemic therapy for hepatocellular carcinoma. , 2001, Seminars in oncology.

[30]  C. R. Hill,et al.  Histological changes in rat liver tumours treated with high-intensity focused ultrasound. , 1993, Ultrasound in medicine & biology.

[31]  R. Busuttil,et al.  Current Treatment Modalities for Hepatocellular Carcinoma , 1994, Annals of surgery.

[32]  Wen-zhi Chen,et al.  Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound. , 2001, Ultrasound in medicine & biology.

[33]  T. Murakami,et al.  Treatment of hepatocellular carcinoma by chemoembolization: evaluation with 3DFT MR imaging. , 1993, AJR. American journal of roentgenology.

[34]  L. Palma.  Diagnostic imaging and interventional therapy of hepatocellular carcinoma. , 1998, The British journal of radiology.

[35]  G. Gazelle,et al.  Thermal ablation therapy for focal malignancy: a unified approach to underlying principles, techniques, and diagnostic imaging guidance. , 2000, AJR. American journal of roentgenology.

[36]  S. Okada.  Transcatheter arterial embolization for advanced hepatocellular carcinoma: The controversy continues , 1998, Hepatology.

[37]  G. Gazelle,et al.  Tumor ablation with radio-frequency energy. , 2000, Radiology.

[38]  Kenji Ikeda,et al.  Effect of repeated transcatheter arterial embolization on the survival time in patients with hepatocellular carcinoma. An analysis by the cox proportional hazard model , 1991, Cancer.

[39]  L. Jover,et al.  Phase II study of transarterial embolization in european patients with hepatocellular carcinoma: Need for controlled trials , 1994, Hepatology.

[40]  T. Nomura,et al.  Susceptibility of experimental autoimmune hepatitis in transgenic mice overexpressing the c‐H‐ras gene , 1997, Journal of gastroenterology and hepatology.

[41]  V. Mazzaferro,et al.  Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. , 1996, The New England journal of medicine.

[42]  C. Bartolozzi,et al.  Hepatocellular carcinoma: CT and MR features after transcatheter arterial embolization and percutaneous ethanol injection. , 1994, Radiology.