Hepatocellular Carcinoma: Targeted Therapy and Multidisciplinary P12

7 Evidence-Based Guidelines for Treatment of Hepatocellular Carcinoma in Japan 95 Revisions of the Guidelines Based on the Latest Knowledge There have been remarkable advances in the management of HCC recently, and the content of parts of the 2005 version of the guidelines, which was based on the literature as of 2002, has become outdated. The work of adding new knowledge and evidence discovered in the period 2003–2007 and revising them is currently under way at present. The widespread adoption of RFA would seem to be the greatest change that can contribute to the treatment algorithm since 2003. RFA enables reliable treat-ment of a larger area via a single puncture and was introduced in Japan around 1999. Since then it has been widely adopted and becoming covered by Japanese national health insurance in April 2004 provided an added boost, so that now it can be said to have replaced PEI. Moreover, the results of RCTs comparing RFA and PEI have been published [14, 15], and the superiority of RFA over PEI appears to have been established as evidence level Ib. Accordingly, not only the answers to the research question group related to percutaneous ablation treatment cited in the 2005 version but the research questions themselves may become the targets of revision. Evaluation of the efficacy of treatment by liver resection and percutaneous abla-tion treatment has also had an impact on the widespread adoption of RFA. The 2005 version of the treatment algorithm is based on the results of treatment by liver resection and PEI, but now that the superiority of RFA over PEI has been established, a comparison between liver resection and percutaneous ablation treat-ment should be performed based on the results of RFA. The results of two RCTs in 2005–2006 have been reported [16, 17], and both of them concluded that the results of liver resection and percutaneous ablation treatment were equivalent. However, there were major problems with both of them, including in their design, and neither of them could be regarded as providing adequate evidence [18]. A paper compar-ing the outcome of liver resection, RFA, and PEI based on a nationwide follow-up survey by the Liver Cancer Study Group of Japan has recently been published [19]. Although the results showed that liver resection was significantly better in cases of recurrence, the differences in survival were not significant; however, the short follow-up period was a problem. The conduct of a high-quality RCT that is able to rigorously evaluate the outcome of RFA and liver resection is awaited in the future. The recommendations of the Japanese guideline about liver transplantation are based on the results of deceased liver transplantation outside Japan. There is a rapid increase in the number of living-donor liver transplantations for HCC in Japan since 1999 [20]. Thus, the recommendations should be amended in an algorithm that reflects their results. Moreover, the results of an RCT that showed the efficacy of a multikinase inhibitor (Sorafenib) against advanced HCC were reported in 2008 [21]. Since there has never been a drug whose efficacy against HCC was demonstrated by a statis-tically significant difference in as sufficient a number of cases as in this study, it generated considerable interest. 96 K. Hasegawa and N. Kokudo Conclusion Because many effective methods are available to treat HCC and the balance between tumor status and liver function status must be taken into consideration, the judgment of skilled specialists is required to make the choice of treatment. On the other hand, the principle of treatment selection based on the hopes and preferences of patients, socioeconomic circumstances, etc., is also important. The treatment algorithm of the Japanese guideline extracts evidence at and above a certain level and reflects it, and it is useful for explaining the complex decision-making process to patients in a way that is easy to comprehend, and for obtaining their understanding in clinical settings, where time is limited. References 1. Makuuchi M, Kokudo N (2006) Clinical practice guidelines for hepatocellular carcinoma: the first evidence based guidelines from Japan. World J Gastroenterol 12:828–829 2. Makuuchi M, Kokudo N, Arii S et al (2008) Development of evidence-based clinical guide-lines for the diagnosis and treatment of hepatocellular carcinoma in Japan. Hepatol Res 38:37–51 3. Liver Cancer Study Group of Japan (1997) Classification of primary liver cancer. Kanehara & Co., Ltd., Tokyo p. 21 4. Makuuchi M, Kosuge T, Takayama T et al (1993) Surgery for small liver cancers. Semin Surg Oncol 9:298–304 5. Llovet JM, Brú C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19:329–338 6. Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42: 1208–1236 7. Ishizawa T, Hasegawa K, Aoki T et al (2008) Multiple tumors and concomitant portal hyper-tension are not operative contraindications for hepatocellular carcinoma. Gastroenterology 134:1908–1916 8. Vauthey JN, Lauwers GY, Esnaola NF et al (2002) Simplified staging for hepatocellular carcinoma. J Clin Oncol 20:1527–1536 9. Arii S, Yamaoka Y, Futagawa S et al (2000) Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. Hepatology 32:1224–1229 10. Llovet JM, Real MI, Montaña X et al (2002) Arterial embolisation or chemoembolisa-tion versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet 359:1734–1739 11. Minagawa M, Makuuchi M, Takayama T et al (2001) Selection criteria for hepatectomy in patients with hepatocellular carcinoma and portal vein tumor thrombus. Ann Surg 233: 379–384 12. Eddy DM (1990) Clinical decision making: from theory to practice. Designing a practice policy. Standards, guidelines, and options. JAMA 263:3077, 3081, 3084 13. Kokudo N, Sasaki Y, Nakayama T et al (2007) Dissemination of evidence-based clinical prac-tice guidelines for hepatocellular carcinoma among Japanese hepatologists, liver surgeons, and primary care physicians. Gut 56:1020–1021 14. Lencioni RA, Allgaier HP, Cioni D et al (2003) Small hepatocellular carcinoma in cirrho-sis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 228:235–240 7 Evidence-Based Guidelines for Treatment of Hepatocellular Carcinoma in Japan 97 15. Shiina S, Teratani T, Obi S et al (2005) A randomized controlled trial of radiofrequency abla-tionwithethanol injectionfor smallhepatocellularcarcinoma.Gastroenterology 129:122–130 16. Huang GT, Lee PH, Tsang YM et al (2005) Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg 242:36–42 17. Chen MS, Li JQ, Zheng Y et al (2006) A prospective randomized trial comparing percuta-neous local ablative therapy and partial hepatectomy for hepatocellular carcinoma. Ann Surg 243:321–328 18. Hasegawa K, Kokudo N, Makuuchi M (2008) Surgery or ablation for hepatocellular carci-noma? Ann Surg 247:557–558 19. Hasegawa K, Makuuchi M, Takayama T, et al. for the Liver Cancer Study Group of Japan (2008) Surgical resection vs. percutaneous ablation for hepatocellular carcinoma: a preliminary report of the Japanese nationwide survey. J Hepatol 49:589–594 20. Todo S, Furukawa H, Tada M; Japanese Liver Transplantation Study Group (2007) Extending indication: role of living donor liver transplantation for hepatocellular carcinoma. Liver Transpl 13(11 Suppl 2): S48–S54 21. Llovet JM, Ricci S, Mazzaferro V, et al. for SHARP Investigators Study Group (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–390 Chapter 8 Hepatocellular Carcinoma Arising in the Non-viral, Non-alcoholic Liver Charles E. Woodall, Robert C.G. Martin, Kelly M. McMasters, and Charles R. Scoggins Keywords HCC risk factors · HCC in the non-fibrotic liver · Non-cirrhotic hepatoma · Fibrolamellar carcinoma (FLC) · Hereditary hemochromatosis (HH) · Non-alcoholic fatty liver disease (NAFLD) Hepatocellular carcinoma is one of the five most common cancers worldwide and is one of the top three in regard to annual mortality. Greater than 80% occur in either sub-Saharan Africa or East Asia, and most of these cases are attributed to viral hepatitis. Increased public awareness and educational campaigns have led to decreasingincidences intheseendemicareas.However, therateofHCCinanumber of areas with traditionally low rates of viral hepatitis, including Australia, the United States, Canada, and the United Kingdom, has increased significantly. This rising incidence cannot be easily explained by changes in immigration, hepatitis C virus, or ethanol. Risk Factors for Hepatocellular Carcinoma It is widely known that chronic hepatitis B and C virus infection remains the most dominant risk factor in HCC incidence. Other well-known hepatocellular carci-nomariskfactorsincludealcoholiccirrhosisandcarcinogenexposure.Theuniversal belief has always been that cirrhosis precedes the development of HCC, even in the United States where continued reports state that approximately 95% of HCC arises in the background of cirrhosis [1]. Indeed, most cases of HCC occur in the setting of cirrhosis, thus impacting the treatment modalities available. However, some cases of HCC arise in a normal liver in patients with no history of alcoholism and negative viral serologies. A certain proportion of these cases are R.C.G. Martin ( ) Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA K.M. McMasters, J.-N. Vauthey (eds.), Hepatocellular Carcinoma, 99 DOI 10.1007/978-1-60327-522-4_8, C Springer Science+Business Media, LLC 2011 ... - tailieumienphi.vn