Hepatocellular Carcinomaintroduction

A diagnosis of hepatocellular carcinoma (HCC) implies a poor prognosis. HCC is the cause of 250,000 deaths worldwide each year. Early HCC is typically clinically silent, and the disease is often well advanced at the first manifestation. Since the introduction of surveillance in patients at high risk of developing HCC, the diagnosis of small HCC has increased, especially in endemic areas such as in parts of Asia. Without treatment, there is a 5-year survival rate of less than 5% (Llovet et al. 1999b; Ulner 2000). According to the World Health Organization, by the year 2010, HCC will have surpassed lung cancer as the foremost cause of cancer mortality. The increasing incidence may be related to the wide-

T. F. Jakobs, MD; R.-T. Hoffmann, MD; M. F. Reiser, MD, Professor

Department of Clinical Radiology, University Hospitals -Grosshadern, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany T. K. Helmberger, MD

Professor, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Klinikum Bogenhausen, Engelschalkinger Strasse 77, 81925 Munich, Germany spread transmission of viral hepatitis, specifically of types B and C, during the 1970s and early 1980s, when illicit use of intravenous narcotics, needle sharing, unsafe sexual activity, and transfusion of unsafe blood and blood products were common practices (Bruix et al. 2001). Patients with liver cirrhosis are at greatest risk for developing HCC and should be monitored every 6 months to detect the tumor at an asymptomatic stage (Bruix and Llovet 2002). The Barcelona-Clinic Liver Cancer (BCLC) group has developed a system that stratifies patients into four categories based on performance status, severity of liver dysfunction caused by the underlying cirrhosis, and the kind of tumor involvement, thus simultaneously setting prognosis and guiding treatment (Llovet et al. 1999a). In the BCLC staging classification, patients who have early-stage HCC, who have a good performance status, Child-Pugh class A or B cirrhosis and an asymptomatic single tumor smaller than 5 cm or as many as three lesions, each smaller than 3 cm are referred to radiofrequency ablation (RFA) (Fig. 3.3.1) (Llovet et al. 1999a).

These patients should be considered for any of the available radical treatment options, such as surgical resection, liver transplantation, or percutaneous techniques of tumor ablation (Bruix et al. 2001). However, surgical resection is only suitable for 9%-27% of patients with HCC because of their poor hepatic reserve due to the underlying chronic liver disease with significant portal hypertension and abnormal bilirubin levels or multifocal distribution of tumor nodules (Bruix and Llovet 2002; Fan et al. 1995; Lai et al. 1995; Liver CanceR Study Group of Japan 1990; Llovet et al. 1999a). Orthotopic liver transplantation (OLT) is a strategy that can treat both HCC and liver dysfunction, and indeed has shown excellent survival in patients at an early stage of the cancer (Llovet et al. 1999c; Mazzaf eRRo et al. 1996). However, with an increasing demand for donor organs but a limited supply,

Fig. 3.3.1. This flowchart illustrates the algorithm used for selecting the appropriate treatment option for patients with hepatocellular carcinoma (HCC) including surgical resection, transplantation, radiofrequency ablation (RFA), transarte-rial chemoembolization (TACE), new agents such as selective internal radiation therapy (SIRT), systemic therapy and best supportive care. RFA is offered to patients with early-stage HCC with a single tumor smaller than 5 cm or as many as three lesions, each smaller than 3 cm, good performance status and evidence for neither vascular invasion nor extrahepatic tumor spread based on clinical and imaging findings. (M Metastases, N nodules, PEI percutaneous ethanol injection, PST performance status test.) *Cadaveric liver transplantation or living donor liver transplantation With permission from LLovet et al. (2003) Lancet 362:1907-1917

Fig. 3.3.1. This flowchart illustrates the algorithm used for selecting the appropriate treatment option for patients with hepatocellular carcinoma (HCC) including surgical resection, transplantation, radiofrequency ablation (RFA), transarte-rial chemoembolization (TACE), new agents such as selective internal radiation therapy (SIRT), systemic therapy and best supportive care. RFA is offered to patients with early-stage HCC with a single tumor smaller than 5 cm or as many as three lesions, each smaller than 3 cm, good performance status and evidence for neither vascular invasion nor extrahepatic tumor spread based on clinical and imaging findings. (M Metastases, N nodules, PEI percutaneous ethanol injection, PST performance status test.) *Cadaveric liver transplantation or living donor liver transplantation With permission from LLovet et al. (2003) Lancet 362:1907-1917

the waiting time for an OLT is now longer then 1 year in Europe and the United States (LLovet et al. 1999c; Sarasin et al. 1998). Living donor liver transplantation is still at an early stage of clinical application (Bruix and Llovet 2002). Regarding these issues, percutaneous ablation plays a major role in the management of early-stage HCC (Lencioni et al. 2004, 2005; Tateishi et al. 2005b).

Various percutaneous, locoregional therapeutic modalities have been developed and tested clinically over recent years for the treatment of HCC. These include intratumoral injection of ethanol or acetic acid and thermal ablation with RF, laser, microwaves, or cryosurgery. Percutaneous ethanol injection (PEI), more frequently performed in the past, is considered to be effective for the treatment of relatively small-sized, encapsulated early-stage HCC and therefore may achieve 5-year survival rates of 32%-47% (Lencioni et al. 1995; Livraghi et al. 1995). The major limitation of PEI is the high local recurrence rate that may reach up to 43% (Koda et al. 2000).

RFA has emerged as the most powerful alternative method for percutaneous ablation (GadalETa et al. 2004; Ginams 2003, 2005; Goldberg and Ahmed 2002; Raut et al. 2005) and is rapidly gaining importance worldwide as the percutaneous treatment of choice for patients with early-stage tumors. A tumor nodule <3 cm in diameter can be ablated with a single application of RFA (GoldbErg et al. 1996). The predictability of the ablation area is one of the major advantages of RFA compared with PEI. The treatment efficacy and complication rate have been described in numerous studies (MorEno Planas et al. 2005; CHen et al. 2005).

Patients who have a more advanced, multi-nodular HCC with neither evidence of vascular invasion nor extrahepatic spread are classified as having intermediate-stage HCC according to the BCLC staging system (Llovet et al. 1999a). Transarterial chemo-embolization (TACE) is an accepted and worldwide-used palliative treatment option for patients with intermediate-stage HCC (Bruix et al. 1998; LloveT et al. 2002, 2003). Due to recent advances in RF technology, RFA also has been used to treat patients with intermediate-stage tumors. Preliminary reports have shown that RFA performed after balloon catheter occlusion of the hepatic artery, transarterial embo-lization, or chemoembolization results in increased volumes of coagulation necrosis, thus enabling successful destruction of large HCC lesions (Yamasaki et al. 2005; de Baere et al. 2002; Akamatsu et al. 2004; Qian et al. 2003; Kurokohchi et al. 2004).

This chapter reviews the current status of percutaneous, image-guided RFA in the management of HCC by discussing technical issues and clinical results in the treatment of early- and intermediate-stage HCC.

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