2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma

Korean Liver Cancer Study Group (KLCSG), National Cancer Center, Korea (NCC), Korean Liver Cancer Study Group (KLCSG), National Cancer Center, Korea (NCC)

Abstract

The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.

Keywords: Carcinoma, hepatocellular; Guidelines; Management.

Figures

Fig. 1
Fig. 1
Annual cases and incidence rate of hepatocellular carcinoma.
Fig. 2
Fig. 2
Changes in the 5-year survival rates of overall cancers and hepatocellular carcinoma (HCC).
Fig. 3
Fig. 3
Diagnostic algorithm. US, ultrasonography; HBV, hepatitis B virus; HCV, hepatitis C virus; AFP, α-fetoprotein; HCC, hepatocellular carcinoma; CT, computed tomography; MRI, magnetic resonance imaging; Gd-EOB-DTPA, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid. *HCC radiological hallmarks include arterial phase enhancement with washout in the portal or delayed phase; †For the diagnosis of nodules 1–2 cm in diameter, two or more imaging modalities are required if a suboptimal imaging technique is used.
Fig. 4
Fig. 4
First-line treatment according to the 2014 KLCSG-NCC Korea Practice Guidelines for patients with HCC, Child-Pugh class A, no portal hypertension, and ECOG performance status 0–1. KLCSG, Korean Liver Cancer Study Group; NCC, National Cancer Center; HCC, hepatocellular carcinoma; ECOG, Eastern Cooperative Oncology Group; mUICC, modified Union for International Cancer Control; RFA, radiofrequency ablation; TACE, transarterial chemoembolization; PEIT, percutaneous ethanol injection therapy; EBRT, external-beam radiation therapy; LT, liver transplantation; DDLT, deceased donor LT; LDLT, living donor liver transplantation; VI, vascular or bile duct invasion.

References

    1. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–926. doi: 10.1136/.
    1. Guyatt GH, Oxman AD, Kunz R, et al. What is “quality of evidence” and why is it important to clinicians? BMJ. 2008;336:995–998. doi: 10.1136/.
    1. Guyatt GH, Oxman AD, Kunz R, et al. Going from evidence to recommendations. BMJ. 2008;336:1049–1051. doi: 10.1136/.
    1. Schünemann HJ, Oxman AD, Brozek J, et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336:1106–1110. doi: 10.1136/.
    1. Brouwers MC, Kho ME, Browman GP, et al. Development of the AGREE II, part 1: performance, usefulness and areas for improvement. CMAJ. 2010;182:1045–1052. doi: 10.1503/cmaj.091714.
    1. Brouwers MC, Kho ME, Browman GP, et al. Development of the AGREE II, part 2: assessment of validity of items and tools to support application. CMAJ. 2010;182:E472–E478. doi: 10.1503/cmaj.091716.
    1. National Cancer Control Institute. Cancer facts and figures 2011 [Internet] Goyang: National Cancer Center; 2011. [cited 2014 Mar 26]. Available from: .
    1. National Cancer Control Institute. Cancer facts and figures 2010 [Internet] Goyang: National Cancer Center; 2011. [cited 2014 Mar 26]. Available from: .
    1. Korean Association for the Study of the Liver. White paper on liver diseases in Korea. Seoul: Korean Association for the Study of the Liver; 2013.
    1. Korean Statistical Information Service. Statistical database 2012 [Internet] Daejeon: Statistics Korea; c2014. [cited 2014 Mar 26]. Available from: .
    1. Llovet JM, Bustamante J, Castells A, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology. 1999;29:62–67. doi: 10.1002/hep.510290145.
    1. The Korean Liver Cancer Study Group; Korean Central Cancer Registry. A nationwide random sample study 2010 [Internet] Seoul: The Korean Liver Cancer Study Group; 2010. [cited 2014 Mar 26]. Available from: .
    1. Kwak HW, Park JW, Nam BH, et al. Clinical outcomes of a cohort series of patients with hepatocellular carcinoma in a hepatitis B virus-endemic area. J Gastroenterol Hepatol. 2014;29:820–829. doi: 10.1111/jgh.12470.
    1. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–1255. doi: 10.1016/S0140-6736(11)61347-0.
    1. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–1127. doi: 10.1056/NEJMra1001683.
    1. Welzel TM, Graubard BI, Zeuzem S, El-Serag HB, Davila JA, McGlynn KA. Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-Medicare database. Hepatology. 2011;54:463–471. doi: 10.1002/hep.24397.
    1. Hainaut P, Boyle P. Curbing the liver cancer epidemic in Africa. Lancet. 2008;371:367–368. doi: 10.1016/S0140-6736(08)60181-6.
    1. Ioannou GN, Splan MF, Weiss NS, McDonald GB, Beretta L, Lee SP. Incidence and predictors of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2007;5:938–945.e4. doi: 10.1016/j.cgh.2007.02.039.
    1. Sangiovanni A, Prati GM, Fasani P, et al. The natural history of compensated cirrhosis due to hepatitis C virus: a 17-year cohort study of 214 patients. Hepatology. 2006;43:1303–1310. doi: 10.1002/hep.21176.
    1. Chang MH, You SL, Chen CJ, et al. Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study. J Natl Cancer Inst. 2009;101:1348–1355. doi: 10.1093/jnci/djp288.
    1. WHO Publication. Hepatitis B vaccines: WHO position paper-- recommendations. Vaccine. 2010;28:589–590. doi: 10.1016/j.vaccine.2009.10.110.
    1. Korean Association for the Study of the Liver. KASL clinical practice guidelines: management of chronic hepatitis B. Clin Mol Hepatol. 2012;18:109–162. doi: 10.3350/cmh.2012.18.2.109.
    1. Niederau C, Heintges T, Lange S, et al. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med. 1996;334:1422–1427. doi: 10.1056/NEJM199605303342202.
    1. Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521–1531. doi: 10.1056/NEJMoa033364.
    1. Thiele M, Gluud LL, Dahl EK, Krag A. Antiviral therapy for prevention of hepatocellular carcinoma and mortality in chronic hepatitis B: systematic review and meta-analysis. BMJ Open. 2013;3:e003265. doi: 10.1136/bmjopen-2013-003265.
    1. Hosaka T, Suzuki F, Kobayashi M, et al. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection. Hepatology. 2013;58:98–107. doi: 10.1002/hep.26180.
    1. Nishiguchi S, Kuroki T, Nakatani S, et al. Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet. 1995;346:1051–1055. doi: 10.1016/S0140-6736(95)91739-X.
    1. Valla DC, Chevallier M, Marcellin P, et al. Treatment of hepatitis C virus-related cirrhosis: a randomized, controlled trial of interferon alfa-2b versus no treatment. Hepatology. 1999;29:1870–1875. doi: 10.1002/hep.510290616.
    1. Singal AG, Volk ML, Jensen D, Di Bisceglie AM, Schoenfeld PS. A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus. Clin Gastroenterol Hepatol. 2010;8:280–288.e1. doi: 10.1016/j.cgh.2009.11.018.
    1. Lok AS, Everhart JE, Wright EC, et al. Maintenance peginterferon therapy and other factors associated with hepatocellular carcinoma in patients with advanced hepatitis C. Gastroenterology. 2011;140:840–849. doi: 10.1053/j.gastro.2010.11.050.
    1. Di Bisceglie AM, Shiffman ML, Everson GT, et al. Prolonged therapy of advanced chronic hepatitis C with low-dose peginterferon. N Engl J Med. 2008;359:2429–2441. doi: 10.1056/NEJMoa0707615.
    1. Bruix J, Poynard T, Colombo M, et al. Maintenance therapy with peginterferon alfa-2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis C. Gastroenterology. 2011;140:1990–1999. doi: 10.1053/j.gastro.2011.03.010.
    1. Yin J, Li N, Han Y, et al. Effect of antiviral treatment with nucleotide/nucleoside analogs on postoperative prognosis of hepatitis B virus-related hepatocellular carcinoma: a two-stage longitudinal clinical study. J Clin Oncol. 2013;31:3647–3655. doi: 10.1200/JCO.2012.48.5896.
    1. Chen LT, Chen MF, Li LA, et al. Long-term results of a randomized, observation-controlled, phase III trial of adjuvant interferon Alfa-2b in hepatocellular carcinoma after curative resection. Ann Surg. 2012;255:8–17. doi: 10.1097/SLA.0b013e3182363ff9.
    1. Wong JS, Wong GL, Tsoi KK, et al. Meta-analysis: the efficacy of anti-viral therapy in prevention of recurrence after curative treatment of chronic hepatitis B-related hepatocellular carcinoma. Aliment Pharmacol Ther. 2011;33:1104–1112. doi: 10.1111/j.1365-2036.2011.04634.x.
    1. Miao RY, Zhao HT, Yang HY, et al. Postoperative adjuvant antiviral therapy for hepatitis B/C virus-related hepatocellular carcinoma: a meta-analysis. World J Gastroenterol. 2010;16:2931–2942. doi: 10.3748/wjg.v16.i23.2931.
    1. Shiratori Y, Shiina S, Teratani T, et al. Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus. Ann Intern Med. 2003;138:299–306. doi: 10.7326/0003-4819-138-4-200302180-00008.
    1. Mazzaferro V, Romito R, Schiavo M, et al. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology. 2006;44:1543–1554. doi: 10.1002/hep.21415.
    1. Marrero JA, Fontana RJ, Fu S, Conjeevaram HS, Su GL, Lok AS. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J Hepatol. 2005;42:218–224. doi: 10.1016/j.jhep.2004.10.005.
    1. El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology. 2004;126:460–468. doi: 10.1053/j.gastro.2003.10.065.
    1. Bravi F, Bosetti C, Tavani A, Gallus S, La Vecchia C. Coffee reduces risk for hepatocellular carcinoma: an updated meta-analysis. Clin Gastroenterol Hepatol. 2013;11:1413–1421.e1. doi: 10.1016/j.cgh.2013.04.039.
    1. Singal A, Volk ML, Waljee A, et al. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis. Aliment Pharmacol Ther. 2009;30:37–47. doi: 10.1111/j.1365-2036.2009.04014.x.
    1. Andersson KL, Salomon JA, Goldie SJ, Chung RT. Cost effectiveness of alternative surveillance strategies for hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2008;6:1418–1424. doi: 10.1016/j.cgh.2008.08.005.
    1. Zhang BH, Yang BH, Tang ZY. Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol. 2004;130:417–422. doi: 10.1007/s00432-004-0552-0.
    1. Kudo M, Izumi N, Kokudo N, et al. Management of hepatocellular carcinoma in Japan: consensus-based clinical practice guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis. 2011;29:339–364. doi: 10.1159/000327577.
    1. Kim MJ, Bae KW, Seo PJ, et al. Optimal cut-off value of PIVKA-II for diagnosis of hepatocellular carcinoma: using ROC curve. Korean J Hepatol. 2006;12:404–411.
    1. Yoon YJ, Han KH, Kim C, et al. Clinical efficacy of serum PIVKA-II in the diagnosis and follow up after treatment of hepatocellular carcinoma. Korean J Hepatol. 2002;8:465–471.
    1. Omata M, Lesmana LA, Tateishi R, et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int. 2010;4:439–474. doi: 10.1007/s12072-010-9165-7.
    1. Wong GL, Chan HL, Tse YK, et al. On-treatment alpha-fetoprotein is a specific tumor marker for hepatocellular carcinoma in patients with chronic hepatitis B receiving entecavir. Hepatology. 2014;59:986–995. doi: 10.1002/hep.26739.
    1. Krinsky GA, Lee VS, Theise ND, et al. Transplantation for hepatocellular carcinoma and cirrhosis: sensitivity of magnetic resonance imaging. Liver Transpl. 2002;8:1156–1164. doi: 10.1053/jlts.2002.35670.
    1. Zacherl J, Pokieser P, Wrba F, et al. Accuracy of multiphasic helical computed tomography and intraoperative sonography in patients undergoing orthotopic liver transplantation for hepatoma: what is the truth? Ann Surg. 2002;235:528–532. doi: 10.1097/00000658-200204000-00011.
    1. Kim SH, Choi BI, Lee JY, et al. Diagnostic accuracy of multi-/single-detector row CT and contrast-enhanced MRI in the detection of hepatocellular carcinomas meeting the Milan criteria before liver transplantation. Intervirology. 2008;51(Suppl 1):52–60. doi: 10.1159/000122598.
    1. Makuuchi M, Kokudo N, Arii S, et al. Development of evidence-based clinical guidelines for the diagnosis and treatment of hepatocellular carcinoma in Japan. Hepatol Res. 2008;38:37–51. doi: 10.1111/j.1872-034X.2007.00216.x.
    1. Colli A, Fraquelli M, Casazza G, et al. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a systematic review. Am J Gastroenterol. 2006;101:513–523. doi: 10.1111/j.1572-0241.2006.00467.x.
    1. Piscaglia F, Bolondi L. Recent advances in the diagnosis of hepatocellular carcinoma. Hepatol Res. 2007;37(Suppl 2):S178–S192. doi: 10.1111/j.1872-034X.2007.00183.x.
    1. Lee MH, Kim SH, Park MJ, Park CK, Rhim H. Gadoxetic acid-enhanced hepatobiliary phase MRI and high-b-value diffusion-weighted imaging to distinguish well-differentiated hepatocellular carcinomas from benign nodules in patients with chronic liver disease. AJR Am J Roentgenol. 2011;197:W868–W875. doi: 10.2214/AJR.10.6237.
    1. Kim JE, Kim SH, Lee SJ, Rhim H. Hypervascular hepatocellular carcinoma 1 cm or smaller in patients with chronic liver disease: characterization with gadoxetic acid-enhanced MRI that includes diffusion-weighted imaging. AJR Am J Roentgenol. 2011;196:W758–W765. doi: 10.2214/AJR.10.4394.
    1. European Association for the Study of the Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–943. doi: 10.1016/j.jhep.2011.12.001.
    1. Park JW, Kim JH, Kim SK, et al. A prospective evaluation of 18F-FDG and 11C-acetate PET/CT for detection of primary and metastatic hepatocellular carcinoma. J Nucl Med. 2008;49:1912–1921. doi: 10.2967/jnumed.108.055087.
    1. Kojiro M, Roskams T. Early hepatocellular carcinoma and dysplastic nodules. Semin Liver Dis. 2005;25:133–142. doi: 10.1055/s-2005-871193.
    1. Matsui O. Detection and characterization of hepatocellular carcinoma by imaging. Clin Gastroenterol Hepatol. 2005;3(10 Suppl 2):S136–S140. doi: 10.1016/S1542-3565(05)00707-X.
    1. Korean Liver Cancer Study Group; National Cancer Center. Practice guidelines for management of hepatocellular carcinoma 2009. Korean J Hepatol. 2009;15:391–423. doi: 10.3350/kjhep.2009.15.3.391.
    1. Roskams T, Kojiro M. Pathology of early hepatocellular carcinoma: conventional and molecular diagnosis. Semin Liver Dis. 2010;30:17–25. doi: 10.1055/s-0030-1247129.
    1. Forner A, Vilana R, Ayuso C, et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology. 2008;47:97–104. doi: 10.1002/hep.21966.
    1. Stigliano R, Marelli L, Yu D, Davies N, Patch D, Burroughs AK. Seeding following percutaneous diagnostic and therapeutic approaches for hepatocellular carcinoma: what is the risk and the outcome? Seeding risk for percutaneous approach of HCC. Cancer Treat Rev. 2007;33:437–447. doi: 10.1016/j.ctrv.2007.04.001.
    1. Silva MA, Hegab B, Hyde C, Guo B, Buckels JA, Mirza DF. Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis. Gut. 2008;57:1592–1596. doi: 10.1136/gut.2008.149062.
    1. Bae SY, Choi MS, Gwak GY, et al. Comparison of usefulness of clinical diagnostic criteria for hepatocellular carcinoma in a hepatitis B endemic area. Clin Mol Hepatol. 2012;18:185–194. doi: 10.3350/cmh.2012.18.2.185.
    1. Pierce DA, Preston DL. Radiation-related cancer risks at low doses among atomic bomb survivors. Radiat Res. 2000;154:178–186. doi: 10.1667/0033-7587(2000)154[0178:RRCRAL];2.
    1. Preston DL, Shimizu Y, Pierce DA, Suyama A, Mabuchi K. Studies of mortality of atomic bomb survivors. Report 13: solid cancer and noncancer disease mortality: 1950–1997. Radiat Res. 2003;160:381–407. doi: 10.1667/RR3049.
    1. Sont WN, Zielinski JM, Ashmore JP, et al. First analysis of cancer incidence and occupational radiation exposure based on the National Dose Registry of Canada. Am J Epidemiol. 2001;153:309–318. doi: 10.1093/aje/153.4.309.
    1. Cardis E, Vrijheid M, Blettner M, et al. Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries. BMJ. 2005;331:77. doi: 10.1136/bmj.38499.599861.E0.
    1. Gilbert ES. Invited commentary: studies of workers exposed to low doses of radiation. Am J Epidemiol. 2001;153:319–322. doi: 10.1093/aje/153.4.319.
    1. Upton AC National Coluncil on Radiation Protection and Measurements Scientific Committee 1–6. The state of the art in the 1990’s: NCRP report No. 136 on the scientific bases for linearity in the dose-response relationship for ionizing radiation. Health Phys. 2003;85:15–22. doi: 10.1097/00004032-200307000-00005.
    1. Huda W, Ogden KM, Khorasani MR. Converting dose-length product to effective dose at CT. Radiology. 2008;248:995–1003. doi: 10.1148/radiol.2483071964.
    1. National Research Council. Health risks from exposure to low levels of ionizing radiation: BEIR VII, phase 2. Washington, DC: National Academies Press; 2006. Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation.
    1. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP. 2007;37:1–332.
    1. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44:217–231. doi: 10.1016/j.jhep.2005.10.013.
    1. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37:429–442. doi: 10.1053/jhep.2003.50047.
    1. Meier V, Ramadori G. Clinical staging of hepatocellular carcinoma. Dig Dis. 2009;27:131–141. doi: 10.1159/000218345.
    1. Ueno S, Tanabe G, Nuruki K, et al. Prognostic performance of the new classification of primary liver cancer of Japan (4th edition) for patients with hepatocellular carcinoma: a validation analysis. Hepatol Res. 2002;24:395–403. doi: 10.1016/S1386-6346(02)00144-4.
    1. Liver Cancer Study Group of Japan. General rules for the clinical and pathological study of primary liver cancer. 3rd English ed. Tokyo: Kanehara; 2010.
    1. Koh DW, Park JW, Oh SE, et al. Characteristics of the patients with extrahepatic metastases developed in modified UICC T1–T2 stage hepatocellular carcinoma. Paper presented at: Asian Pacific Association for the Study of the Liver Annual Meeting; Kyoto, Japan. 2007. Abtract P-0573.
    1. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology. 2005;42:1208–1236. doi: 10.1002/hep.20933.
    1. Lang H, Sotiropoulos GC, Domland M, et al. Liver resection for hepatocellular carcinoma in non-cirrhotic liver without underlying viral hepatitis. Br J Surg. 2005;92:198–202. doi: 10.1002/bjs.4763.
    1. Capussotti L, Muratore A, Massucco P, Ferrero A, Polastri R, Bouzari H. Major liver resections for hepatocellular carcinoma on cirrhosis: early and long-term outcomes. Liver Transpl. 2004;10(2 Suppl 1):S64–S68. doi: 10.1002/lt.20035.
    1. Poon RT, Fan ST, Lo CM, et al. Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Ann Surg. 2001;234:63–70. doi: 10.1097/00000658-200107000-00010.
    1. Andreou A, Vauthey JN, Cherqui D, et al. Improved long-term survival after major resection for hepatocellular carcinoma: a multicenter analysis based on a new definition of major hepatectomy. J Gastrointest Surg. 2013;17:66–77. doi: 10.1007/s11605-012-2005-4.
    1. Kim JH, Choi DW, Kim SB. Saftey and long-term outcome following major hepatectomy for hepatocellular carcinoma combined with compensated liver cirrhosis. J Korean Surg Soc. 2006;70:444–450.
    1. Huang J, Zhang Y, Peng Z, et al. A modified TNM-7 staging system to better predict the survival in patients with hepatocellular carcinoma after hepatectomy. J Cancer Res Clin Oncol. 2013;139:1709–1719. doi: 10.1007/s00432-013-1497-y.
    1. Torzilli G, Belghiti J, Kokudo N, et al. A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations? An observational study of the HCC East-West Study Group. Ann Surg. 2013;257:929–937. doi: 10.1097/SLA.0b013e31828329b8.
    1. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–649. doi: 10.1002/bjs.1800600817.
    1. Farges O, Malassagne B, Flejou JF, Balzan S, Sauvanet A, Belghiti J. Risk of major liver resection in patients with underlying chronic liver disease: a reappraisal. Ann Surg. 1999;229:210–215. doi: 10.1097/00000658-199902000-00008.
    1. Belghiti J, Hiramatsu K, Benoist S, Massault P, Sauvanet A, Farges O. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg. 2000;191:38–46. doi: 10.1016/S1072-7515(00)00261-1.
    1. Makuuchi M, Sano K. The surgical approach to HCC: our progress and results in Japan. Liver Transpl. 2004;10(2 Suppl 1):S46–S52. doi: 10.1002/lt.20044.
    1. Fan ST, Lai EC, Lo CM, Ng IO, Wong J. Hospital mortality of major hepatectomy for hepatocellular carcinoma associated with cirrhosis. Arch Surg. 1995;130:198–203. doi: 10.1001/archsurg.1995.01430020088017.
    1. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30:1434–1440. doi: 10.1002/hep.510300629.
    1. An M, Park JW, Shin JA, et al. The adverse effect of indirectly diagnosed portal hypertension on the complications and prognosis after hepatic resection of hepatocellular carcinoma. Korean J Hepatol. 2006;12:553–561.
    1. Choi GH, Park JY, Hwang HK, et al. Predictive factors for long-term survival in patients with clinically significant portal hypertension following resection of hepatocellular carcinoma. Liver Int. 2011;31:485–493. doi: 10.1111/j.1478-3231.2010.02436.x.
    1. Capussotti L, Ferrero A, Viganò L, Muratore A, Polastri R, Bouzari H. Portal hypertension: contraindication to liver surgery? World J Surg. 2006;30:992–999. doi: 10.1007/s00268-005-0524-9.
    1. Ishizawa T, Hasegawa K, Aoki T, et al. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology. 2008;134:1908–1916. doi: 10.1053/j.gastro.2008.02.091.
    1. Cucchetti A, Ercolani G, Vivarelli M, et al. Is portal hypertension a contraindication to hepatic resection? Ann Surg. 2009;250:922–928. doi: 10.1097/SLA.0b013e3181b977a5.
    1. Guglielmi A, Ruzzenente A, Conci S, Valdegamberi A, Iacono C. How much remnant is enough in liver resection? Dig Surg. 2012;29:6–17. doi: 10.1159/000335713.
    1. Kim SU, Ahn SH, Park JY, et al. Prediction of postoperative hepatic insufficiency by liver stiffness measurement (FibroScan((R))) before curative resection of hepatocellular carcinoma: a pilot study. Hepatol Int. 2008;2:471–477. doi: 10.1007/s12072-008-9091-0.
    1. Wong JS, Wong GL, Chan AW, et al. Liver stiffness measurement by transient elastography as a predictor on posthepatectomy outcomes. Ann Surg. 2013;257:922–928. doi: 10.1097/SLA.0b013e318269d2ec.
    1. Cescon M, Colecchia A, Cucchetti A, et al. Value of transient elastography measured with FibroScan in predicting the outcome of hepatic resection for hepatocellular carcinoma. Ann Surg. 2012;256:706–712. doi: 10.1097/SLA.0b013e3182724ce8.
    1. Hammerstingl R, Huppertz A, Breuer J, et al. Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions. Eur Radiol. 2008;18:457–467. doi: 10.1007/s00330-007-0716-9.
    1. Kim SH, Kim SH, Lee J, et al. Gadoxetic acid-enhanced MRI versus triple-phase MDCT for the preoperative detection of hepatocellular carcinoma. AJR Am J Roentgenol. 2009;192:1675–1681. doi: 10.2214/AJR.08.1262.
    1. Lin CY, Chen JH, Liang JA, Lin CC, Jeng LB, Kao CH. 18F-FDG PET or PET/CT for detecting extrahepatic metastases or recurrent hepatocellular carcinoma: a systematic review and meta-analysis. Eur J Radiol. 2012;81:2417–2422. doi: 10.1016/j.ejrad.2011.08.004.
    1. Koneru B, Teperman LW, Manzarbeitia C, et al. A multicenter evaluation of utility of chest computed tomography and bone scans in liver transplant candidates with stages I and II hepatoma. Ann Surg. 2005;241:622–628. doi: 10.1097/01.sla.0000157267.27356.80.
    1. Kim IS, Lim YS, Yoon HK, et al. The effect of preoperative transarterial chemoembolization on the patient’s outcome in resectable hepatocellular carcinoma. Korean J Med. 2005;69:614–621.
    1. Wu CC, Ho YZ, Ho WL, Wu TC, Liu TJ, P’eng FK. Preoperative transcatheter arterial chemoembolization for resectable large hepatocellular carcinoma: a reappraisal. Br J Surg. 1995;82:122–126. doi: 10.1002/bjs.1800820141.
    1. Farges O, Belghiti J, Kianmanesh R, et al. Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg. 2003;237:208–217. doi: 10.1097/01.SLA.0000048447.16651.7B.
    1. Tanaka H, Hirohashi K, Kubo S, Shuto T, Higaki I, Kinoshita H. Preoperative portal vein embolization improves prognosis after right hepatectomy for hepatocellular carcinoma in patients with impaired hepatic function. Br J Surg. 2000;87:879–882. doi: 10.1046/j.1365-2168.2000.01438.x.
    1. Liu L, Wang Z, Jiang S, et al. Perioperative allogenenic blood transfusion is associated with worse clinical outcomes for hepatocellular carcinoma: a meta-analysis. PLoS One. 2013;8:e64261. doi: 10.1371/journal.pone.0064261.
    1. Tsujita E, Taketomi A, Kitagawa D, et al. Selective hepatic vascular exclusion for the hepatic resection of HCC. Hepatogastroenterology. 2007;54:527–530.
    1. Eguchi S, Kanematsu T, Arii S, et al. Comparison of the outcomes between an anatomical subsegmentectomy and a non-anatomical minor hepatectomy for single hepatocellular carcinomas based on a Japanese nationwide survey. Surgery. 2008;143:469–475. doi: 10.1016/j.surg.2007.12.003.
    1. Tanaka K, Shimada H, Matsumoto C, et al. Anatomic versus limited nonanatomic resection for solitary hepatocellular carcinoma. Surgery. 2008;143:607–615. doi: 10.1016/j.surg.2008.01.006.
    1. Shi M, Guo RP, Lin XJ, et al. Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma: a prospective randomized trial. Ann Surg. 2007;245:36–43. doi: 10.1097/01.sla.0000231758.07868.71.
    1. Poon RT, Fan ST, Ng IO, Wong J. Significance of resection margin in hepatectomy for hepatocellular carcinoma: a critical reappraisal. Ann Surg. 2000;231:544–551. doi: 10.1097/00000658-200004000-00014.
    1. Suh KS. Systematic hepatectomy for small hepatocellular carcinoma in Korea. J Hepatobiliary Pancreat Surg. 2005;12:365–370. doi: 10.1007/s00534-005-1002-3.
    1. Wakai T, Shirai Y, Sakata J, et al. Anatomic resection independently improves long-term survival in patients with T1–T2 hepatocellular carcinoma. Ann Surg Oncol. 2007;14:1356–1365. doi: 10.1245/s10434-006-9318-z.
    1. Yin Z, Fan X, Ye H, Yin D, Wang J. Short- and long-term outcomes after laparoscopic and open hepatectomy for hepatocellular carcinoma: a global systematic review and meta-analysis. Ann Surg Oncol. 2013;20:1203–1215. doi: 10.1245/s10434-012-2705-8.
    1. Nguyen KT, Gamblin TC, Geller DA. World review of laparoscopic liver resection-2,804 patients. Ann Surg. 2009;250:831–841. doi: 10.1097/SLA.0b013e3181b0c4df.
    1. Lai EC, Yang GP, Tang CN. Robot-assisted laparoscopic liver resection for hepatocellular carcinoma: short-term outcome. Am J Surg. 2013;205:697–702. doi: 10.1016/j.amjsurg.2012.08.015.
    1. Vauthey JN, Lauwers GY, Esnaola NF, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol. 2002;20:1527–1536. doi: 10.1200/JCO.20.6.1527.
    1. Pawlik TM, Poon RT, Abdalla EK, et al. Critical appraisal of the clinical and pathologic predictors of survival after resection of large hepatocellular carcinoma. Arch Surg. 2005;140:450–457. doi: 10.1001/archsurg.140.5.450.
    1. Lee SG, Hwang S, Jung JP, Lee YJ, Kim KH, Ahn CS. Outcome of patients with huge hepatocellular carcinoma after primary resection and treatment of recurrent lesions. Br J Surg. 2007;94:320–326. doi: 10.1002/bjs.5622.
    1. Nishikawa H, Kimura T, Kita R, Osaki Y. Treatment for hepatocellular carcinoma in elderly patients: a literature review. J Cancer. 2013;4:635–643. doi: 10.7150/jca.7279.
    1. Iakova P, Awad SS, Timchenko NA. Aging reduces proliferative capacities of liver by switching pathways of C/EBPalpha growth arrest. Cell. 2003;113:495–506. doi: 10.1016/S0092-8674(03)00318-0.
    1. Mullen JT, Ribero D, Reddy SK, et al. Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergoing major hepatectomy. J Am Coll Surg. 2007;204:854–862. doi: 10.1016/j.jamcollsurg.2006.12.032.
    1. Hai L, Yong-Hong P, Yong F, Ren-Feng L. One-stage liver resection for spontaneous rupture of hepatocellular carcinoma. World J Surg. 2005;29:1316–1318. doi: 10.1007/s00268-005-7626-2.
    1. Bae JH, Hong SW, Heo TG, Lee H. Characteristics and prognosis after resection for ruptured hepatocellular carcinoma. Korean J HBP Surg. 2006;10:37–41.
    1. Buczkowski AK, Kim PT, Ho SG, et al. Multidisciplinary management of ruptured hepatocellular carcinoma. J Gastrointest Surg. 2006;10:379–386. doi: 10.1016/j.gassur.2005.10.012.
    1. Zhu Q, Li J, Yan JJ, Huang L, Wu MC, Yan YQ. Predictors and clinical outcomes for spontaneous rupture of hepatocellular carcinoma. World J Gastroenterol. 2012;18:7302–7307. doi: 10.3748/wjg.v18.i48.7302.
    1. Pawlik TM, Poon RT, Abdalla EK, et al. Hepatectomy for hepatocellular carcinoma with major portal or hepatic vein invasion: results of a multicenter study. Surgery. 2005;137:403–410. doi: 10.1016/j.surg.2004.12.012.
    1. Roayaie S, Jibara G, Taouli B, Schwartz M. Resection of hepatocellular carcinoma with macroscopic vascular invasion. Ann Surg Oncol. 2013;20:3754–3760. doi: 10.1245/s10434-013-3074-7.
    1. Moon DB, Hwang S, Wang HJ, et al. Surgical outcomes of hepatocellular carcinoma with bile duct tumor thrombus: a Korean multicenter study. World J Surg. 2013;37:443–451. doi: 10.1007/s00268-012-1845-0.
    1. Belghiti J, Guevara OA, Noun R, Saldinger PF, Kianmanesh R. Liver hanging maneuver: a safe approach to right hepatectomy without liver mobilization. J Am Coll Surg. 2001;193:109–111. doi: 10.1016/S1072-7515(01)00909-7.
    1. Liu CL, Fan ST, Cheung ST, Lo CM, Ng IO, Wong J. Anterior approach versus conventional approach right hepatic resection for large hepatocellular carcinoma: a prospective randomized controlled study. Ann Surg. 2006;244:194–203. doi: 10.1097/01.sla.0000225095.18754.45.
    1. Minagawa M, Makuuchi M, Takayama T, Kokudo N. Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma. Ann Surg. 2003;238:703–710. doi: 10.1097/01.sla.0000094549.11754.e6.
    1. Finkelstein SD, Marsh W, Demetris AJ, et al. Microdissection-based allelotyping discriminates de novo tumor from intrahepatic spread in hepatocellular carcinoma. Hepatology. 2003;37:871–879. doi: 10.1053/jhep.2003.50134.
    1. Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–207. doi: 10.1016/S0168-8278(02)00360-4.
    1. Zhou L, Rui JA, Wang SB, Chen SG, Qu Q. Prognostic factors of solitary large hepatocellular carcinoma: the importance of differentiation grade. Eur J Surg Oncol. 2011;37:521–525. doi: 10.1016/j.ejso.2011.03.137.
    1. Li SH, Guo ZX, Xiao CZ, et al. Risk factors for early and late intrahepatic recurrence in patients with single hepatocellular carcinoma without macrovascular invasion after curative resection. Asian Pac J Cancer Prev. 2013;14:4759–4763. doi: 10.7314/APJCP.2013.14.8.4759.
    1. Nathan H, Schulick RD, Choti MA, Pawlik TM. Predictors of survival after resection of early hepatocellular carcinoma. Ann Surg. 2009;249:799–805. doi: 10.1097/SLA.0b013e3181a38eb5.
    1. Portolani N, Coniglio A, Ghidoni S, et al. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg. 2006;243:229–235. doi: 10.1097/01.sla.0000197706.21803.a1.
    1. Kaibori M, Ishizaki M, Matsui K, Kwon AH. Predictors of microvascular invasion before hepatectomy for hepatocellular carcinoma. J Surg Oncol. 2010;102:462–468. doi: 10.1002/jso.21631.
    1. Wu JC, Huang YH, Chau GY, et al. Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma. J Hepatol. 2009;51:890–897. doi: 10.1016/j.jhep.2009.07.009.
    1. Kim do Y, Paik YH, Ahn SH, et al. PIVKA-II is a useful tumor marker for recurrent hepatocellular carcinoma after surgical resection. Oncology. 2007;72(Suppl 1):52–57. doi: 10.1159/000111707.
    1. Choi GH, Kim DH, Kang CM, et al. Prognostic factors and optimal treatment strategy for intrahepatic nodular recurrence after curative resection of hepatocellular carcinoma. Ann Surg Oncol. 2008;15:618–629. doi: 10.1245/s10434-007-9671-6.
    1. Nagano Y, Shimada H, Ueda M, et al. Efficacy of repeat hepatic resection for recurrent hepatocellular carcinomas. ANZ J Surg. 2009;79:729–733. doi: 10.1111/j.1445-2197.2009.05059.x.
    1. Huang ZY, Liang BY, Xiong M, et al. Long-term outcomes of repeat hepatic resection in patients with recurrent hepatocellular carcinoma and analysis of recurrent types and their prognosis: a single-center experience in China. Ann Surg Oncol. 2012;19:2515–2525. doi: 10.1245/s10434-012-2269-7.
    1. Chan AC, Chan SC, Chok KS, et al. Treatment strategy for recurrent hepatocellular carcinoma: salvage transplantation, repeated resection, or radiofrequency ablation? Liver Transpl. 2013;19:411–419. doi: 10.1002/lt.23605.
    1. Chan DL, Alzahrani NA, Morris DL, Chua TC. Systematic review of efficacy and outcomes of salvage liver transplantation after primary hepatic resection for hepatocellular carcinoma. J Gastroenterol Hepatol. 2014;29:31–41. doi: 10.1111/jgh.12399.
    1. Katyal S, Oliver JH, 3rd, Peterson MS, Ferris JV, Carr BS, Baron RL. Extrahepatic metastases of hepatocellular carcinoma. Radiology. 2000;216:698–703. doi: 10.1148/radiology.216.3.r00se24698.
    1. Kuo SW, Chang YL, Huang PM, et al. Prognostic factors for pulmonary metastasectomy in hepatocellular carcinoma. Ann Surg Oncol. 2007;14:992–997. doi: 10.1245/s10434-006-9217-3.
    1. Nakagawa T, Kamiyama T, Nakanishi K, et al. Pulmonary resection for metastases from hepatocellular carcinoma: factors influencing prognosis. J Thorac Cardiovasc Surg. 2006;131:1248–1254. doi: 10.1016/j.jtcvs.2006.02.009.
    1. Koneru B, Cassavilla A, Bowman J, Iwatsuki S, Starzl TE. Liver transplantation for malignant tumors. Gastroenterol Clin North Am. 1988;17:177–193.
    1. Iwatsuki S, Starzl TE, Sheahan DG, et al. Hepatic resection versus transplantation for hepatocellular carcinoma. Ann Surg. 1991;214:221–228. doi: 10.1097/00000658-199109000-00005.
    1. Bismuth H, Chiche L, Adam R, Castaing D, Diamond T, Dennison A. Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients. Ann Surg. 1993;218:145–151. doi: 10.1097/00000658-199308000-00005.
    1. Bismuth H, Majno PE, Adam R. Liver transplantation for hepatocellular carcinoma. Semin Liver Dis. 1999;19:311–322. doi: 10.1055/s-2007-1007120.
    1. Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–699. doi: 10.1056/NEJM199603143341104.
    1. Mazzaferro V, Bhoori S, Sposito C, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl. 2011;17(Suppl 2):S44–S57. doi: 10.1002/lt.22365.
    1. European Liver Transplant Registry (ELTR) [Internet] Villejuif Cedex: European Liver Transplant Registry; 2014. [cited 2014 Feb 18]. Available from:
    1. Organ Procurement and Transplantation Network (OPTN) [Internet] Richmond: Organ Procurement and Transplantation Network; 2014. [cited 2014 Feb 18]. Available from:
    1. Germani G, Gurusamy K, Garcovich M, et al. Which matters most: number of tumors, size of the largest tumor, or total tumor volume? Liver Transpl. 2011;17(Suppl 2):S58–S66. doi: 10.1002/lt.22336.
    1. Sugimachi K, Shirabe K, Taketomi A, et al. Prognostic significance of preoperative imaging in recipients of living donor liver transplantation for hepatocellular carcinoma. Transplantation. 2011;91:570–574. doi: 10.1097/TP.0b013e318208134e.
    1. Lee JM, Trevisani F, Vilgrain V, Wald C. Imaging diagnosis and staging of hepatocellular carcinoma. Liver Transpl. 2011;17(Suppl 2):S34–S43. doi: 10.1002/lt.22369.
    1. Yang SH, Suh KS, Lee HW, et al. The role of (18)F-FDG-PET imaging for the selection of liver transplantation candidates among hepatocellular carcinoma patients. Liver Transpl. 2006;12:1655–1660. doi: 10.1002/lt.20861.
    1. Kornberg A, Freesmeyer M, Barthel E, et al. 18F-FDG-uptake of hepatocellular carcinoma on PET predicts microvascular tumor invasion in liver transplant patients. Am J Transplant. 2009;9:592–600. doi: 10.1111/j.1600-6143.2008.02516.x.
    1. Clavien PA, Lesurtel M, Bossuyt PM, et al. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol. 2012;13:e11–e22. doi: 10.1016/S1470-2045(11)70175-9.
    1. Freeman RB, Jr, Wiesner RH, Harper A, et al. The new liver allocation system: moving toward evidence-based transplantation policy. Liver Transpl. 2002;8:851–858. doi: 10.1053/jlts.2002.35927.
    1. Pomfret EA, Washburn K, Wald C, et al. Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transpl. 2010;16:262–278. doi: 10.1002/lt.21999.
    1. Korean Network for Organ Sharing (KONOS) [Internet] Seoul: Korean Network for Organ Sharing; 2014. [cited 2014 Mar 18]. Available from:
    1. Hwang S, Lee SG, Joh JW, Suh KS, Kim DG. Liver transplantation for adult patients with hepatocellular carcinoma in Korea: comparison between cadaveric donor and living donor liver transplantations. Liver Transpl. 2005;11:1265–1272. doi: 10.1002/lt.20549.
    1. Kim MS. Comparison between Status with CTP score and MELD score in allocation of deceased donor liver: Korean national-based survey. Paper presented at: 2013 Congress of Asian Society of Transplantation; Kyoto, Japan. 2013.
    1. Kim MS. Research for modification of emergency status in deceased donor liver allocation: development of revised MELD score system. Cheongju: Korea Centers for Disease Control and Prevention; 2014.
    1. Roayaie S, Frischer JS, Emre SH, et al. Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters. Ann Surg. 2002;235:533–539. doi: 10.1097/00000658-200204000-00012.
    1. Llovet JM, Bruix J. Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol. 2008;48(Suppl 1):S20–S37. doi: 10.1016/j.jhep.2008.01.022.
    1. Samuel D, Colombo M, El-Serag H, Sobesky R, Heaton N. Toward optimizing the indications for orthotopic liver transplantation in hepatocellular carcinoma. Liver Transpl. 2011;17(Suppl 2):S6–S13. doi: 10.1002/lt.22423.
    1. Ioannou GN, Perkins JD, Carithers RL., Jr Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival. Gastroenterology. 2008;134:1342–1351. doi: 10.1053/j.gastro.2008.02.013.
    1. Volk ML, Vijan S, Marrero JA. A novel model measuring the harm of transplanting hepatocellular carcinoma exceeding Milan criteria. Am J Transplant. 2008;8:839–846. doi: 10.1111/j.1600-6143.2007.02138.x.
    1. Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33:1394–1403. doi: 10.1053/jhep.2001.24563.
    1. Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10:35–43. doi: 10.1016/S1470-2045(08)70284-5.
    1. Vibert E, Azoulay D, Hoti E, et al. Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. Am J Transplant. 2010;10:129–137. doi: 10.1111/j.1600-6143.2009.02750.x.
    1. Toso C, Trotter J, Wei A, et al. Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma. Liver Transpl. 2008;14:1107–1115. doi: 10.1002/lt.21484.
    1. Mazzaferro V, Battiston C, Perrone S, et al. Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study. Ann Surg. 2004;240:900–909. doi: 10.1097/01.sla.0000143301.56154.95.
    1. Llovet JM, Mas X, Aponte JJ, et al. Cost effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation. Gut. 2002;50:123–128. doi: 10.1136/gut.50.1.123.
    1. Yao FY, Bass NM, Nikolai B, et al. Liver transplantation for hepatocellular carcinoma: analysis of survival according to the intention-to-treat principle and dropout from the waiting list. Liver Transpl. 2002;8:873–883. doi: 10.1053/jlts.2002.34923.
    1. Yao FY, Kerlan RK, Jr, Hirose R, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology. 2008;48:819–827. doi: 10.1002/hep.22412.
    1. Decaens T, Roudot-Thoraval F, Bresson-Hadni S, et al. Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma. Liver Transpl. 2005;11:767–775. doi: 10.1002/lt.20418.
    1. Porrett PM, Peterman H, Rosen M, et al. Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era. Liver Transpl. 2006;12:665–673. doi: 10.1002/lt.20636.
    1. Lesurtel M, Müllhaupt B, Pestalozzi BC, Pfammatter T, Clavien PA. Transarterial chemoembolization as a bridge to liver transplantation for hepatocellular carcinoma: an evidence-based analysis. Am J Transplant. 2006;6:2644–2650. doi: 10.1111/j.1600-6143.2006.01509.x.
    1. Pelletier SJ, Fu S, Thyagarajan V, et al. An intention-to-treat analysis of liver transplantation for hepatocellular carcinoma using organ procurement transplant network data. Liver Transpl. 2009;15:859–868. doi: 10.1002/lt.21778.
    1. Cucchetti A, Cescon M, Bigonzi E, et al. Priority of candidates with hepatocellular carcinoma awaiting liver transplantation can be reduced after successful bridge therapy. Liver Transpl. 2011;17:1344–1354. doi: 10.1002/lt.22397.
    1. De Luna W, Sze DY, Ahmed A, et al. Transarterial chemoinfusion for hepatocellular carcinoma as downstaging therapy and a bridge toward liver transplantation. Am J Transplant. 2009;9:1158–1168. doi: 10.1111/j.1600-6143.2009.02576.x.
    1. Freeman RB, Jr, Steffick DE, Guidinger MK, Farmer DG, Berg CL, Merion RM. Liver and intestine transplantation in the United States, 1997–2006. Am J Transplant. 2008;8(4 Pt 2):958–976. doi: 10.1111/j.1600-6143.2008.02174.x.
    1. O’Connor JK, Trotter J, Davis GL, Dempster J, Klintmalm GB, Goldstein RM. Long-term outcomes of stereotactic body radiation therapy in the treatment of hepatocellular cancer as a bridge to transplantation. Liver Transpl. 2012;18:949–954. doi: 10.1002/lt.23439.
    1. Bush DA, Kayali Z, Grove R, Slater JD. The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. Cancer. 2011;117:3053–3059. doi: 10.1002/cncr.25809.
    1. Katz AW, Chawla S, Qu Z, Kashyap R, Milano MT, Hezel AF. Stereotactic hypofractionated radiation therapy as a bridge to transplantation for hepatocellular carcinoma: clinical outcome and pathologic correlation. Int J Radiat Oncol Biol Phys. 2012;83:895–900. doi: 10.1016/j.ijrobp.2011.08.032.
    1. Ravaioli M, Grazi GL, Piscaglia F, et al. Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant. 2008;8:2547–2557. doi: 10.1111/j.1600-6143.2008.02409.x.
    1. Chapman WC, Majella Doyle MB, Stuart JE, et al. Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation. Ann Surg. 2008;248:617–625.
    1. Yao FY, Hirose R, LaBerge JM, et al. A prospective study on downstaging of hepatocellular carcinoma prior to liver transplantation. Liver Transpl. 2005;11:1505–1514. doi: 10.1002/lt.20526.
    1. Bhoori S, Sposito C, Germini A, Coppa J, Mazzaferro V. The challenges of liver transplantation for hepatocellular carcinoma on cirrhosis. Transpl Int. 2010;23:712–722. doi: 10.1111/j.1432-2277.2010.01111.x.
    1. Lewandowski RJ, Kulik LM, Riaz A, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant. 2009;9:1920–1928. doi: 10.1111/j.1600-6143.2009.02695.x.
    1. Korean Organ Donation Agency (KODA) [Internet] Seoul: Korean Organ Donation Agency; 2014. [cited 2014 May 12]. Available from:
    1. Hwang S, Lee SG, Belghiti J. Liver transplantation for HCC: its role: Eastern and Western perspectives. J Hepatobiliary Pancreat Sci. 2010;17:443–448. doi: 10.1007/s00534-009-0241-0.
    1. Grant RC, Sandhu L, Dixon PR, Greig PD, Grant DR, McGilvray ID. Living vs. deceased donor liver transplantation for hepatocellular carcinoma: a systematic review and meta-analysis. Clin Transplant. 2013;27:140–147. doi: 10.1111/ctr.12031.
    1. Kulik LM, Fisher RA, Rodrigo DR, et al. Outcomes of living and deceased donor liver transplant recipients with hepatocellular carcinoma: results of the A2ALL cohort. Am J Transplant. 2012;12:2997–3007. doi: 10.1111/j.1600-6143.2012.04272.x.
    1. Kulik L, Abecassis M. Living donor liver transplantation for hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S277–S282. doi: 10.1053/j.gastro.2004.09.042.
    1. Sarasin FP, Majno PE, Llovet JM, Bruix J, Mentha G, Hadengue A. Living donor liver transplantation for early hepatocellular carcinoma: a life-expectancy and cost-effectiveness perspective. Hepatology. 2001;33:1073–1079. doi: 10.1053/jhep.2001.23311.
    1. Lee SG, Hwang S, Moon DB, et al. Expanded indication criteria of living donor liver transplantation for hepatocellular carcinoma at one large-volume center. Liver Transpl. 2008;14:935–945. doi: 10.1002/lt.21445.
    1. Choi HJ, Kim DG, Na GH, Han JH, Hong TH, You YK. Clinical outcome in patients with hepatocellular carcinoma after living-donor liver transplantation. World J Gastroenterol. 2013;19:4737–4744. doi: 10.3748/wjg.v19.i29.4737.
    1. Suh KS, Cho EH, Lee HW, Shin WY, Yi NJ, Lee KU. Liver transplantation for hepatocellular carcinoma in patients who do not meet the Milan criteria. Dig Dis. 2007;25:329–333. doi: 10.1159/000106913.
    1. Kwon CH, Kim DJ, Han YS, et al. HCC in living donor liver transplantation: can we expand the Milan criteria? Dig Dis. 2007;25:313–319. doi: 10.1159/000106911.
    1. Sugawara Y, Tamura S, Makuuchi M. Living donor liver transplantation for hepatocellular carcinoma: Tokyo University series. Dig Dis. 2007;25:310–312. doi: 10.1159/000106910.
    1. Ito T, Takada Y, Ueda M, et al. Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation. Liver Transpl. 2007;13:1637–1644. doi: 10.1002/lt.21281.
    1. Taketomi A, Sanefuji K, Soejima Y, et al. Impact of des-gamma-carboxy prothrombin and tumor size on the recurrence of hepatocellular carcinoma after living donor liver transplantation. Transplantation. 2009;87:531–537. doi: 10.1097/TP.0b013e3181943bee.
    1. Todo S, Furukawa H, Tada M Japanese Liver Transplantation Study Group. Extending indication: role of living donor liver transplantation for hepatocellular carcinoma. Liver Transpl. 2007;13(11 Suppl 2):S48–S54. doi: 10.1002/lt.21334.
    1. Siegler M, Simmerling MC, Siegler JH, Cronin DC., 2nd Recipient deaths during donor surgery: a new ethical problem in living donor liver transplantation (LDLT) Liver Transpl. 2006;12:358–360. doi: 10.1002/lt.20670.
    1. Ghobrial RM, Freise CE, Trotter JF, et al. Donor morbidity after living donation for liver transplantation. Gastroenterology. 2008;135:468–476. doi: 10.1053/j.gastro.2008.04.018.
    1. Brown RS., Jr Live donors in liver transplantation. Gastroenterology. 2008;134:1802–1813. doi: 10.1053/j.gastro.2008.02.092.
    1. Yi NJ, Suh KS, Cho JY, et al. Three-quarters of right liver donors experienced postoperative complications. Liver Transpl. 2007;13:797–806. doi: 10.1002/lt.21030.
    1. Kim KH, Jung DH, Park KM, et al. Comparison of open and laparoscopic live donor left lateral sectionectomy. Br J Surg. 2011;98:1302–1308. doi: 10.1002/bjs.7601.
    1. Hwang S, Lee SG, Lee YJ, et al. Lessons learned from 1,000 living donor liver transplantations in a single center: how to make living donations safe. Liver Transpl. 2006;12:920–927. doi: 10.1002/lt.20734.
    1. Kim SJ, Na GH, Choi HJ, Yoo YK, Kim DG. Surgical outcome of right liver donors in living donor liver transplantation: single-center experience with 500 cases. J Gastrointest Surg. 2012;16:1160–1170. doi: 10.1007/s11605-012-1865-y.
    1. Kim SH, Kim YK. Improving outcomes of living-donor right hepatectomy. Br J Surg. 2013;100:528–534. doi: 10.1002/bjs.9022.
    1. Shin M, Song S, Kim JM, et al. Donor morbidity including biliary complications in living-donor liver transplantation: single-center analysis of 827 cases. Transplantation. 2012;93:942–948. doi: 10.1097/TP.0b013e31824ad5de.
    1. Chan SC, Chan AC, Sharr WW, et al. Perpetuating proficiency in donor right hepatectomy for living donor liver transplantation. Asian J Surg. 2014;37:65–72. doi: 10.1016/j.asjsur.2013.09.001.
    1. Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg. 2002;235:373–382. doi: 10.1097/00000658-200203000-00009.
    1. Fuks D, Dokmak S, Paradis V, Diouf M, Durand F, Belghiti J. Benefit of initial resection of hepatocellular carcinoma followed by transplantation in case of recurrence: an intention-to-treat analysis. Hepatology. 2012;55:132–140. doi: 10.1002/hep.24680.
    1. Sapisochin G, Castells L, Dopazo C, et al. Single HCC in cirrhotic patients: liver resection or liver transplantation? Long-term outcome according to an intention-to-treat basis. Ann Surg Oncol. 2013;20:1194–1202. doi: 10.1245/s10434-012-2655-1.
    1. Cucchetti A, Vitale A, Del Gaudio M, et al. Harm and benefits of primary liver resection and salvage transplantation for hepatocellular carcinoma. Am J Transplant. 2010;10:619–627. doi: 10.1111/j.1600-6143.2009.02984.x.
    1. Hu Z, Wang W, Li Z, Ye S, Zheng SS. Recipient outcomes of salvage liver transplantation versus primary liver transplantation: a systematic review and meta-analysis. Liver Transpl. 2012;18:1316–1323. doi: 10.1002/lt.23521.
    1. Liu F, Wei Y, Wang W, et al. Salvage liver transplantation for recurrent hepatocellular carcinoma within UCSF criteria after liver resection. PLoS One. 2012;7:e48932. doi: 10.1371/journal.pone.0048932.
    1. Moon JI, Kwon CH, Joh JW, et al. Primary versus salvage living donor liver transplantation for patients with hepatocellular carcinoma: impact of microvascular invasion on survival. Transplant Proc. 2012;44:487–493. doi: 10.1016/j.transproceed.2011.11.009.
    1. Hwang S, Lee SG, Moon DB, et al. Salvage living donor liver transplantation after prior liver resection for hepatocellular carcinoma. Liver Transpl. 2007;13:741–746. doi: 10.1002/lt.21157.
    1. Kim BW, Park YK, Kim YB, Wang HJ, Kim MW. Salvage liver transplantation for recurrent hepatocellular carcinoma after liver resection: feasibility of the Milan criteria and operative risk. Transplant Proc. 2008;40:3558–3561. doi: 10.1016/j.transproceed.2008.03.175.
    1. Kaido T, Mori A, Ogura Y, et al. Living donor liver transplantation for recurrent hepatocellular carcinoma after liver resection. Surgery. 2012;151:55–60. doi: 10.1016/j.surg.2011.06.032.
    1. Wu L, Hu A, Tam N, et al. Salvage liver transplantation for patients with recurrent hepatocellular carcinoma after curative resection. PLoS One. 2012;7:e41820. doi: 10.1371/journal.pone.0041820.
    1. Li HY, Wei YG, Yan LN, Li B. Salvage liver transplantation in the treatment of hepatocellular carcinoma: a meta-analysis. World J Gastroenterol. 2012;18:2415–2422. doi: 10.3748/wjg.v18.i19.2415.
    1. Schwartz M, Roayaie S, Llovet J. How should patients with hepatocellular carcinoma recurrence after liver transplantation be treated? J Hepatol. 2005;43:584–589. doi: 10.1016/j.jhep.2005.07.019.
    1. Zimmerman MA, Trotter JF, Wachs M, et al. Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma. Liver Transpl. 2008;14:633–638. doi: 10.1002/lt.21420.
    1. Toso C, Meeberg GA, Bigam DL, et al. De novo sirolimus-based immunosuppression after liver transplantation for hepatocellular carcinoma: long-term outcomes and side effects. Transplantation. 2007;83:1162–1168. doi: 10.1097/01.tp.0000262607.95372.e0.
    1. Liang W, Wang D, Ling X, et al. Sirolimus-based immunosuppression in liver transplantation for hepatocellular carcinoma: a meta-analysis. Liver Transpl. 2012;18:62–69. doi: 10.1002/lt.22441.
    1. Sala M, Llovet JM, Vilana R, et al. Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma. Hepatology. 2004;40:1352–1360. doi: 10.1002/hep.20465.
    1. Livraghi T, Meloni F, Di Stasi M, et al. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice? Hepatology. 2008;47:82–89. doi: 10.1002/hep.21933.
    1. Lencioni R, Cioni D, Crocetti L, et al. Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation. Radiology. 2005;234:961–967. doi: 10.1148/radiol.2343040350.
    1. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or =4 cm. Gastroenterology. 2004;127:1714–1723. doi: 10.1053/j.gastro.2004.09.003.
    1. Shiina S, Teratani T, Obi S, et al. A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology. 2005;129:122–130. doi: 10.1053/j.gastro.2005.04.009.
    1. Lencioni RA, Allgaier HP, Cioni D, et al. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology. 2003;228:235–240. doi: 10.1148/radiol.2281020718.
    1. Kim YS, Lim HK, Rhim H, et al. Ten-year outcomes of percutaneous radiofrequency ablation as first-line therapy of early hepatocellular carcinoma: analysis of prognostic factors. J Hepatol. 2013;58:89–97. doi: 10.1016/j.jhep.2012.09.020.
    1. Shiina S, Tateishi R, Arano T, et al. Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J Gastroenterol. 2012;107:569–577. doi: 10.1038/ajg.2011.425.
    1. de Baère T, Risse O, Kuoch V, et al. Adverse events during radiofrequency treatment of 582 hepatic tumors. AJR Am J Roentgenol. 2003;181:695–700. doi: 10.2214/ajr.181.3.1810695.
    1. Rhim H, Yoon KH, Lee JM, et al. Major complications after radio-frequency thermal ablation of hepatic tumors: spectrum of imaging findings. Radiographics. 2003;23:123–134. doi: 10.1148/rg.231025054.
    1. Song I, Rhim H, Lim HK, Kim YS, Choi D. Percutaneous radiofrequency ablation of hepatocellular carcinoma abutting the diaphragm and gastrointestinal tracts with the use of artificial ascites: safety and technical efficacy in 143 patients. Eur Radiol. 2009;19:2630–2640. doi: 10.1007/s00330-009-1463-x.
    1. Lee MW, Rhim H, Cha DI, Kim YJ, Lim HK. Planning US for percutaneous radiofrequency ablation of small hepatocellular carcinomas (1–3 cm): value of fusion imaging with conventional US and CT/MR images. J Vasc Interv Radiol. 2013;24:958–965. doi: 10.1016/j.jvir.2013.04.007.
    1. Kudo M, Hatanaka K, Maekawa K. Newly developed novel ultrasound technique, defect reperfusion ultrasound imaging, using sonazoid in the management of hepatocellular carcinoma. Oncology. 2010;78(Suppl 1):40–45. doi: 10.1159/000315229.
    1. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut. 2005;54:1151–1156. doi: 10.1136/gut.2004.045203.
    1. Brunello F, Veltri A, Carucci P, et al. Radiofrequency ablation versus ethanol injection for early hepatocellular carcinoma: a randomized controlled trial. Scand J Gastroenterol. 2008;43:727–735. doi: 10.1080/00365520701885481.
    1. Cho YK, Kim JK, Kim MY, Rhim H, Han JK. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology. 2009;49:453–459. doi: 10.1002/hep.22648.
    1. Chen MS, Li JQ, Zheng Y, et al. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg. 2006;243:321–328. doi: 10.1097/01.sla.0000201480.65519.b8.
    1. Feng K, Yan J, Li X, et al. A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol. 2012;57:794–802. doi: 10.1016/j.jhep.2012.05.007.
    1. Huang J, Yan L, Cheng Z, et al. A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg. 2010;252:903–912. doi: 10.1097/SLA.0b013e3181efc656.
    1. Qi X, Tang Y, An D, et al. Radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma: a meta-analysis of randomized controlled trials. J Clin Gastroenterol. 2014;48:450–457.
    1. Cho YK, Kim JK, Kim WT, Chung JW. Hepatic resection versus radiofrequency ablation for very early stage hepatocellular carcinoma: a Markov model analysis. Hepatology. 2010;51:1284–1290. doi: 10.1002/hep.23466.
    1. Shibata T, Isoda H, Hirokawa Y, Arizono S, Shimada K, Togashi K. Small hepatocellular carcinoma: is radiofrequency ablation combined with transcatheter arterial chemoembolization more effective than radiofrequency ablation alone for treatment? Radiology. 2009;252:905–913. doi: 10.1148/radiol.2523081676.
    1. Morimoto M, Numata K, Kondou M, Nozaki A, Morita S, Tanaka K. Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization. Cancer. 2010;116:5452–5460. doi: 10.1002/cncr.25314.
    1. Lu Z, Wen F, Guo Q, Liang H, Mao X, Sun H. Radiofrequency ablation plus chemoembolization versus radiofrequency ablation alone for hepatocellular carcinoma: a meta-analysis of randomized-controlled trials. Eur J Gastroenterol Hepatol. 2013;25:187–194. doi: 10.1097/MEG.0b013e32835a0a07.
    1. Ni JY, Liu SS, Xu LF, Sun HL, Chen YT. Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma. World J Gastroenterol. 2013;19:3872–3882. doi: 10.3748/wjg.v19.i24.3872.
    1. Ho CM, Lee PH, Shau WY, Ho MC, Wu YM, Hu RH. Survival in patients with recurrent hepatocellular carcinoma after primary hepatectomy: comparative effectiveness of treatment modalities. Surgery. 2012;151:700–709. doi: 10.1016/j.surg.2011.12.015.
    1. Liang HH, Chen MS, Peng ZW, et al. Percutaneous radiofrequency ablation versus repeat hepatectomy for recurrent hepatocellular carcinoma: a retrospective study. Ann Surg Oncol. 2008;15:3484–3493. doi: 10.1245/s10434-008-0076-y.
    1. Chan AC, Poon RT, Cheung TT, et al. Survival analysis of re-resection versus radiofrequency ablation for intrahepatic recurrence after hepatectomy for hepatocellular carcinoma. World J Surg. 2012;36:151–156. doi: 10.1007/s00268-011-1323-0.
    1. Cha DI, Lee MW, Rhim H, Choi D, Kim YS, Lim HK. Therapeutic efficacy and safety of percutaneous ethanol injection with or without combined radiofrequency ablation for hepatocellular carcinomas in high risk locations. Korean J Radiol. 2013;14:240–247. doi: 10.3348/kjr.2013.14.2.240.
    1. Ishii H, Okada S, Nose H, et al. Local recurrence of hepatocellular carcinoma after percutaneous ethanol injection. Cancer. 1996;77:1792–1796. doi: 10.1002/(SICI)1097-0142(19960501)77:9<1792::AID-CNCR6>;2-E.
    1. Vilana R, Bruix J, Bru C, Ayuso C, Sole M, Rodes J. Tumor size determines the efficacy of percutaneous ethanol injection for the treatment of small hepatocellular carcinoma. Hepatology. 1992;16:353–357. doi: 10.1002/hep.1840160212.
    1. Livraghi T, Bolondi L, Lazzaroni S, et al. Percutaneous ethanol injection in the treatment of hepatocellular carcinoma in cirrhosis: a study on 207 patients. Cancer. 1992;69:925–929. doi: 10.1002/1097-0142(19920215)69:4<925::AID-CNCR2820690415>;2-G.
    1. Daniele B, De Sio I, Izzo F, et al. Hepatic resection and percutaneous ethanol injection as treatments of small hepatocellular carcinoma: a Cancer of the Liver Italian Program (CLIP 08) retrospective case-control study. J Clin Gastroenterol. 2003;36:63–67. doi: 10.1097/00004836-200301000-00017.
    1. Huang GT, Lee PH, Tsang YM, et al. Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg. 2005;242:36–42. doi: 10.1097/01.sla.0000167925.90380.fe.
    1. Wright AS, Sampson LA, Warner TF, Mahvi DM, Lee FT., Jr Radiofrequency versus microwave ablation in a hepatic porcine model. Radiology. 2005;236:132–139. doi: 10.1148/radiol.2361031249.
    1. Lubner MG, Brace CL, Hinshaw JL, Lee FT., Jr Microwave tumor ablation: mechanism of action, clinical results, and devices. J Vasc Interv Radiol. 2010;21(8 Suppl):S192–S203. doi: 10.1016/j.jvir.2010.04.007.
    1. Sotiropoulos GC, Lang H, Frilling A, et al. Resectability of hepatocellular carcinoma: evaluation of 333 consecutive cases at a single hepatobiliary specialty center and systematic review of the literature. Hepatogastroenterology. 2006;53:322–329.
    1. Bargellini I, Florio F, Golfieri R, Grosso M, Lauretti DL, Cioni R. Trends in utilization of transarterial treatments for hepatocellular carcinoma: results of a survey by the italian society of interventional radiology. Cardiovasc Intervent Radiol. 2014;37:438–444. doi: 10.1007/s00270-013-0656-5.
    1. Park JW, Sherman M, Colombo M, et al. Observations of hepatocellular carcinoma (HCC) management patterns from the global HCC bridge study: first characterization of the full study population. J Clin Oncol. 2012;30(Suppl) abstr 4033.
    1. Gaba RC. Chemoembolization practice patterns and technical methods among interventional radiologists: results of an online survey. AJR Am J Roentgenol. 2012;198:692–699. doi: 10.2214/AJR.11.7066.
    1. Satake M, Uchida H, Arai Y, et al. Transcatheter arterial chemoembolization (TACE) with lipiodol to treat hepatocellular carcinoma: survey results from the TACE Study Group of Japan. Cardiovasc Intervent Radiol. 2008;31:756–761. doi: 10.1007/s00270-007-9255-7.
    1. Brown DB, Gould JE, Gervais DA, et al. Transcatheter therapy for hepatic malignancy: standardization of terminology and reporting criteria. J Vasc Interv Radiol. 2009;20(7 Suppl):S425–S434. doi: 10.1016/j.jvir.2009.04.021.
    1. Bruix J, Sala M, Llovet JM. Chemoembolization for hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S179–S188. doi: 10.1053/j.gastro.2004.09.032.
    1. Matsui O, Kadoya M, Yoshikawa J, et al. Small hepatocellular carcinoma: treatment with subsegmental transcatheter arterial embolization. Radiology. 1993;188:79–83. doi: 10.1148/radiology.188.1.8390073.
    1. Llovet JM, Real MI, Montaña X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734–1739. doi: 10.1016/S0140-6736(02)08649-X.
    1. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–1171. doi: 10.1053/jhep.2002.33156.
    1. Takayasu K, Arii S, Ikai I, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology. 2006;131:461–469. doi: 10.1053/j.gastro.2006.05.021.
    1. Ikeda M, Arai Y, Park SJ, et al. Prospective study of transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: an Asian cooperative study between Japan and Korea. J Vasc Interv Radiol. 2013;24:490–500. doi: 10.1016/j.jvir.2013.01.003.
    1. Shim JH, Park JW, Choi JI, Kim HB, Lee WJ, Kim CM. Does postembolization fever after chemoembolization have prognostic significance for survival in patients with unresectable hepatocellular carcinoma? J Vasc Interv Radiol. 2009;20:209–216. doi: 10.1016/j.jvir.2008.10.021.
    1. Chan AO, Yuen MF, Hui CK, Tso WK, Lai CL. A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma. Cancer. 2002;94:1747–1752. doi: 10.1002/cncr.10407.
    1. Miyayama S, Matsui O, Yamashiro M, et al. Ultraselective transcatheter arterial chemoembolization with a 2-f tip microcatheter for small hepatocellular carcinomas: relationship between local tumor recurrence and visualization of the portal vein with iodized oil. J Vasc Interv Radiol. 2007;18:365–376. doi: 10.1016/j.jvir.2006.12.004.
    1. Lee HS, Kim KM, Yoon JH, et al. Therapeutic efficacy of transcatheter arterial chemoembolization as compared with hepatic resection in hepatocellular carcinoma patients with compensated liver function in a hepatitis B virus-endemic area: a prospective cohort study. J Clin Oncol. 2002;20:4459–4465. doi: 10.1200/JCO.2002.02.013.
    1. Bargellini I, Sacco R, Bozzi E, et al. Transarterial chemoembolization in very early and early-stage hepatocellular carcinoma patients excluded from curative treatment: a prospective cohort study. Eur J Radiol. 2012;81:1173–1178. doi: 10.1016/j.ejrad.2011.03.046.
    1. Yang HJ, Lee JH, Lee DH, et al. Small single-nodule hepatocellular carcinoma: comparison of transarterial chemoembolization, radiofrequency ablation, and hepatic resection by using inverse probability weighting. Radiology. 2014;271:909–918. doi: 10.1148/radiol.13131760.
    1. Chung GE, Lee JH, Kim HY, et al. Transarterial chemoembolization can be safely performed in patients with hepatocellular carcinoma invading the main portal vein and may improve the overall survival. Radiology. 2011;258:627–634. doi: 10.1148/radiol.10101058.
    1. Georgiades CS, Hong K, D’Angelo M, Geschwind JF. Safety and efficacy of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol. 2005;16:1653–1659. doi: 10.1097/01.RVI.0000182185.47500.7A.
    1. Lee HS, Kim JS, Choi IJ, Chung JW, Park JH, Kim CY. The safety and efficacy of transcatheter arterial chemoembolization in the treatment of patients with hepatocellular carcinoma and main portal vein obstruction: a prospective controlled study. Cancer. 1997;79:2087–2094. doi: 10.1002/(SICI)1097-0142(19970601)79:11<2087::AID-CNCR5>;2-M.
    1. Chung JW, Park JH, Han JK, Choi BI, Han MC. Hepatocellular carcinoma and portal vein invasion: results of treatment with transcatheter oily chemoembolization. AJR Am J Roentgenol. 1995;165:315–321. doi: 10.2214/ajr.165.2.7618547.
    1. Luo J, Guo RP, Lai EC, et al. Transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a prospective comparative study. Ann Surg Oncol. 2011;18:413–420. doi: 10.1245/s10434-010-1321-8.
    1. Lammer J, Malagari K, Vogl T, et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol. 2010;33:41–52. doi: 10.1007/s00270-009-9711-7.
    1. Varela M, Real MI, Burrel M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007;46:474–481. doi: 10.1016/j.jhep.2006.10.020.
    1. Sacco R, Bargellini I, Bertini M, et al. Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma. J Vasc Interv Radiol. 2011;22:1545–1552. doi: 10.1016/j.jvir.2011.07.002.
    1. Burrel M, Reig M, Forner A, et al. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads: implications for clinical practice and trial design. J Hepatol. 2012;56:1330–1335. doi: 10.1016/j.jhep.2012.01.008.
    1. Malagari K, Pomoni M, Moschouris H, et al. Chemoembolization with doxorubicin-eluting beads for unresectable hepatocellular carcinoma: five-year survival analysis. Cardiovasc Intervent Radiol. 2012;35:1119–1128. doi: 10.1007/s00270-012-0394-0.
    1. Prajapati HJ, Dhanasekaran R, El-Rayes BF, et al. Safety and efficacy of doxorubicin drug-eluting bead transarterial chemoembolization in patients with advanced hepatocellular carcinoma. J Vasc Interv Radiol. 2013;24:307–315. doi: 10.1016/j.jvir.2012.11.026.
    1. Mazzaferro V, Sposito C, Bhoori S, et al. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology. 2013;57:1826–1837. doi: 10.1002/hep.26014.
    1. Salem R, Lewandowski RJ, Mulcahy MF, et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138:52–64. doi: 10.1053/j.gastro.2009.09.006.
    1. Sangro B, Carpanese L, Cianni R, et al. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation. Hepatology. 2011;54:868–878. doi: 10.1002/hep.24451.
    1. Kim DY, Park BJ, Kim YH, et al. Radioembolization with Yttrium-90 resin microspheres in hepatocellular carcinoma: a multicenter prospective study. Am J Clin Oncol. Epub 2013 Sep 21. .
    1. Hawkins MA, Dawson LA. Radiation therapy for hepatocellular carcinoma: from palliation to cure. Cancer. 2006;106:1653–1663. doi: 10.1002/cncr.21811.
    1. Kim TH, Kim DY, Park JW, et al. Dose-volumetric parameters predicting radiation-induced hepatic toxicity in unresectable hepatocellular carcinoma patients treated with three-dimensional conformal radiotherapy. Int J Radiat Oncol Biol Phys. 2007;67:225–231. doi: 10.1016/j.ijrobp.2006.08.015.
    1. Schefter TE, Kavanagh BD, Timmerman RD, Cardenes HR, Baron A, Gaspar LE. A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases. Int J Radiat Oncol Biol Phys. 2005;62:1371–1378. doi: 10.1016/j.ijrobp.2005.01.002.
    1. Pan CC, Kavanagh BD, Dawson LA, et al. Radiation-associated liver injury. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S94–S100. doi: 10.1016/j.ijrobp.2009.06.092.
    1. Andolino DL, Johnson CS, Maluccio M, et al. Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2011;81:e447–e453. doi: 10.1016/j.ijrobp.2011.04.011.
    1. Bujold A, Massey CA, Kim JJ, et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol. 2013;31:1631–1639. doi: 10.1200/JCO.2012.44.1659.
    1. Honda Y, Kimura T, Aikata H, et al. Stereotactic body radiation therapy combined with transcatheter arterial chemoembolization for small hepatocellular carcinoma. J Gastroenterol Hepatol. 2013;28:530–536. doi: 10.1111/jgh.12087.
    1. Huang WY, Jen YM, Lee MS, et al. Stereotactic body radiation therapy in recurrent hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2012;84:355–361. doi: 10.1016/j.ijrobp.2011.11.058.
    1. Kang JK, Kim MS, Cho CK, et al. Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization. Cancer. 2012;118:5424–5431. doi: 10.1002/cncr.27533.
    1. Sanuki N, Takeda A, Oku Y, et al. Stereotactic body radiotherapy for small hepatocellular carcinoma: a retrospective outcome analysis in 185 patients. Acta Oncol. 2014;53:399–404. doi: 10.3109/0284186X.2013.820342.
    1. Yoon SM, Lim YS, Park MJ, et al. Stereotactic body radiation therapy as an alternative treatment for small hepatocellular carcinoma. PLoS One. 2013;8:e79854. doi: 10.1371/journal.pone.0079854.
    1. Fukumitsu N, Sugahara S, Nakayama H, et al. A prospective study of hypofractionated proton beam therapy for patients with hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2009;74:831–836. doi: 10.1016/j.ijrobp.2008.10.073.
    1. Kawashima M, Furuse J, Nishio T, et al. Phase II study of radiotherapy employing proton beam for hepatocellular carcinoma. J Clin Oncol. 2005;23:1839–1846. doi: 10.1200/JCO.2005.00.620.
    1. Komatsu S, Fukumoto T, Demizu Y, et al. Clinical results and risk factors of proton and carbon ion therapy for hepatocellular carcinoma. Cancer. 2011;117:4890–4904. doi: 10.1002/cncr.26134.
    1. Nakayama H, Sugahara S, Tokita M, et al. Proton beam therapy for hepatocellular carcinoma: the University of Tsukuba experience. Cancer. 2009;115:5499–5506. doi: 10.1002/cncr.24619.
    1. Bae SH, Kim MS, Cho CK, et al. Feasibility and efficacy of stereotactic ablative radiotherapy for Barcelona Clinic Liver Cancer-C stage hepatocellular carcinoma. J Korean Med Sci. 2013;28:213–219. doi: 10.3346/jkms.2013.28.2.213.
    1. Cho JY, Paik YH, Park HC, et al. The feasibility of combined transcatheter arterial chemoembolization and radiotherapy for advanced hepatocellular carcinoma. Liver Int. 2014;34:795–801. doi: 10.1111/liv.12445.
    1. Eun HS, Kim MJ, Kim HJ, et al. The retrospective cohort study for survival rate in patients with advanced hepatocellular carcinoma receiving radiotherapy or palliative care. Korean J Hepatol. 2011;17:189–198. doi: 10.3350/kjhep.2011.17.3.189.
    1. Katamura Y, Aikata H, Takaki S, et al. Intra-arterial 5-fluorouracil/interferon combination therapy for advanced hepatocellular carcinoma with or without three-dimensional conformal radiotherapy for portal vein tumor thrombosis. J Gastroenterol. 2009;44:492–502. doi: 10.1007/s00535-009-0033-y.
    1. Kim DY, Park W, Lim DH, et al. Three-dimensional conformal radiotherapy for portal vein thrombosis of hepatocellular carcinoma. Cancer. 2005;103:2419–2426. doi: 10.1002/cncr.21043.
    1. Lo CH, Huang WY, Lee MS, et al. Stereotactic ablative radiotherapy for unresectable hepatocellular carcinoma patients who failed or were unsuitable for transarterial chemoembolization. Eur J Gastroenterol Hepatol. 2014;26:345–352. doi: 10.1097/MEG.0000000000000032.
    1. McIntosh A, Hagspiel KD, Al-Osaimi AM, et al. Accelerated treatment using intensity-modulated radiation therapy plus concurrent capecitabine for unresectable hepatocellular carcinoma. Cancer. 2009;115:5117–5125. doi: 10.1002/cncr.24552.
    1. Shirai S, Sato M, Suwa K, et al. Feasibility and efficacy of single photon emission computed tomography-based three-dimensional conformal radiotherapy for hepatocellular carcinoma 8 cm or more with portal vein tumor thrombus in combination with transcatheter arterial chemoembolization. Int J Radiat Oncol Biol Phys. 2010;76:1037–1044. doi: 10.1016/j.ijrobp.2009.03.023.
    1. Skinner HD, Sharp HJ, Kaseb AO, et al. Radiation treatment outcomes for unresectable hepatocellular carcinoma. Acta Oncol. 2011;50:1191–1198. doi: 10.3109/0284186X.2011.592147.
    1. Sugahara S, Nakayama H, Fukuda K, et al. Proton-beam therapy for hepatocellular carcinoma associated with portal vein tumor thrombosis. Strahlenther Onkol. 2009;185:782–788. doi: 10.1007/s00066-009-2020-x.
    1. Tanaka Y, Nakazawa T, Komori S, et al. Radiotherapy for patients with unresectable advanced hepatocellular carcinoma with invasion to intrahepatic large vessels: efficacy and outcomes. J Gastroenterol Hepatol. 2014;29:352–357. doi: 10.1111/jgh.12333.
    1. Xi M, Zhang L, Zhao L, et al. Effectiveness of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombosis. PLoS One. 2013;8:e63864. doi: 10.1371/journal.pone.0063864.
    1. Yamada K, Izaki K, Sugimoto K, et al. Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2003;57:113–119. doi: 10.1016/S0360-3016(03)00434-6.
    1. Yoon SM, Lim YS, Won HJ, et al. Radiotherapy plus transarterial chemoembolization for hepatocellular carcinoma invading the portal vein: long-term patient outcomes. Int J Radiat Oncol Biol Phys. 2012;82:2004–2011. doi: 10.1016/j.ijrobp.2011.03.019.
    1. Yu JI, Park HC, Lim do H, et al. Prognostic index for portal vein tumor thrombosis in patients with hepatocellular carcinoma treated with radiation therapy. J Korean Med Sci. 2011;26:1014–1022. doi: 10.3346/jkms.2011.26.8.1014.
    1. Hsu HC, Chen TY, Chiu KW, et al. Three-dimensional conformal radiotherapy for the treatment of arteriovenous shunting in patients with hepatocellular carcinoma. Br J Radiol. 2007;80:38–42. doi: 10.1259/bjr/55395102.
    1. Meng MB, Cui YL, Lu Y, et al. Transcatheter arterial chemoembolization in combination with radiotherapy for unresectable hepatocellular carcinoma: a systematic review and meta-analysis. Radiother Oncol. 2009;92:184–194. doi: 10.1016/j.radonc.2008.11.002.
    1. Oh D, Lim do H, Park HC, et al. Early three-dimensional conformal radiotherapy for patients with unresectable hepatocellular carcinoma after incomplete transcatheter arterial chemoembolization: a prospective evaluation of efficacy and toxicity. Am J Clin Oncol. 2010;33:370–375. doi: 10.1097/COC.0b013e3181b0c298.
    1. Seong J, Lee IJ, Shim SJ, et al. A multicenter retrospective cohort study of practice patterns and clinical outcome on radiotherapy for hepatocellular carcinoma in Korea. Liver Int. 2009;29:147–152. doi: 10.1111/j.1478-3231.2008.01873.x.
    1. Tang QH, Li AJ, Yang GM, et al. Surgical resection versus conformal radiotherapy combined with TACE for resectable hepatocellular carcinoma with portal vein tumor thrombus: a comparative study. World J Surg. 2013;37:1362–1370. doi: 10.1007/s00268-013-1969-x.
    1. Koo JE, Kim JH, Lim YS, et al. Combination of transarterial chemoembolization and three-dimensional conformal radiotherapy for hepatocellular carcinoma with inferior vena cava tumor thrombus. Int J Radiat Oncol Biol Phys. 2010;78:180–187. doi: 10.1016/j.ijrobp.2009.07.1730.
    1. Yu JI, Park HC, Lim do H, et al. Scheduled interval trans-catheter arterial chemoembolization followed by radiation therapy in patients with unresectable hepatocellular carcinoma. J Korean Med Sci. 2012;27:736–743. doi: 10.3346/jkms.2012.27.7.736.
    1. Han KH, Seong J, Kim JK, Ahn SH, Lee do Y, Chon CY. Pilot clinical trial of localized concurrent chemoradiation therapy for locally advanced hepatocellular carcinoma with portal vein thrombosis. Cancer. 2008;113:995–1003. doi: 10.1002/cncr.23684.
    1. Park MS, Kim SU, Park JY, et al. Combination treatment of localized concurrent chemoradiation therapy and transarterial chemoembolization in locally advanced hepatocellular carcinoma with intrahepatic metastasis. Cancer Chemother Pharmacol. 2013;71:165–173. doi: 10.1007/s00280-012-1993-9.
    1. Chuma M, Taguchi H, Yamamoto Y, et al. Efficacy of therapy for advanced hepatocellular carcinoma: intra-arterial 5-fluorouracil and subcutaneous interferon with image-guided radiation. J Gastroenterol Hepatol. 2011;26:1123–1132. doi: 10.1111/j.1440-1746.2011.06745.x.
    1. Choi SB, Kim KS, Park YN, et al. The efficacy of hepatic resection after neoadjuvant transarterial chemoembolization (TACE) and radiation therapy in hepatocellular carcinoma greater than 5 cm in size. J Korean Med Sci. 2009;24:242–247. doi: 10.3346/jkms.2009.24.2.242.
    1. Kim TH, Kim DY, Park JW, et al. Three-dimensional conformal radiotherapy of unresectable hepatocellular carcinoma patients for whom transcatheter arterial chemoembolization was ineffective or unsuitable. Am J Clin Oncol. 2006;29:568–575. doi: 10.1097/01.coc.0000239147.60196.11.
    1. Park W, Lim DH, Paik SW, et al. Local radiotherapy for patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2005;61:1143–1150. doi: 10.1016/j.ijrobp.2004.08.028.
    1. Dawson LA, McGinn CJ, Lawrence TS. Conformal chemoradiation for primary and metastatic liver malignancies. Semin Surg Oncol. 2003;21:249–255. doi: 10.1002/ssu.10043.
    1. Cheng SH, Lin YM, Chuang VP, et al. A pilot study of three-dimensional conformal radiotherapy in unresectable hepatocellular carcinoma. J Gastroenterol Hepatol. 1999;14:1025–1033. doi: 10.1046/j.1440-1746.1999.01994.x.
    1. Huang JF, Wang LY, Lin ZY, et al. Incidence and clinical outcome of icteric type hepatocellular carcinoma. J Gastroenterol Hepatol. 2002;17:190–195. doi: 10.1046/j.1440-1746.2002.02677.x.
    1. Jang JW, Kay CS, You CR, et al. Simultaneous multitarget irradiation using helical tomotherapy for advanced hepatocellular carcinoma with multiple extrahepatic metastases. Int J Radiat Oncol Biol Phys. 2009;74:412–418. doi: 10.1016/j.ijrobp.2008.08.034.
    1. Park YJ, Lim do H, Paik SW, et al. Radiation therapy for abdominal lymph node metastasis from hepatocellular carcinoma. J Gastroenterol. 2006;41:1099–1106. doi: 10.1007/s00535-006-1895-x.
    1. Yamashita H, Nakagawa K, Shiraishi K, et al. Radiotherapy for lymph node metastases in patients with hepatocellular carcinoma: retrospective study. J Gastroenterol Hepatol. 2007;22:523–527. doi: 10.1111/j.1440-1746.2006.04450.x.
    1. Yoon SM, Kim JH, Choi EK, et al. Radioresponse of hepatocellular carcinoma-treatment of lymph node metastasis. Cancer Res Treat. 2004;36:79–84. doi: 10.4143/crt.2004.36.1.79.
    1. Zeng ZC, Tang ZY, Fan J, et al. Consideration of role of radiotherapy for lymph node metastases in patients with HCC: retrospective analysis for prognostic factors from 125 patients. Int J Radiat Oncol Biol Phys. 2005;63:1067–1076. doi: 10.1016/j.ijrobp.2005.03.058.
    1. He J, Zeng ZC, Tang ZY, et al. Clinical features and prognostic factors in patients with bone metastases from hepatocellular carcinoma receiving external beam radiotherapy. Cancer. 2009;115:2710–2720. doi: 10.1002/cncr.24300.
    1. Kaizu T, Karasawa K, Tanaka Y, et al. Radiotherapy for osseous metastases from hepatocellular carcinoma: a retrospective study of 57 patients. Am J Gastroenterol. 1998;93:2167–2171. doi: 10.1111/j.1572-0241.1998.00614.x.
    1. Murakami R, Baba Y, Furusawa M, et al. Short communication: the value of embolization therapy in painful osseous metastases from hepatocellular carcinomas: comparative study with radiation therapy. Br J Radiol. 1996;69:1042–1044. doi: 10.1259/0007-1285-69-827-1042.
    1. Seong J, Koom WS, Park HC. Radiotherapy for painful bone metastases from hepatocellular carcinoma. Liver Int. 2005;25:261–265. doi: 10.1111/j.1478-3231.2005.01094.x.
    1. Taki Y, Yamaoka Y, Takayasu T, et al. Bone metastases of hepatocellular carcinoma after liver resection. J Surg Oncol. 1992;50:12–18. doi: 10.1002/jso.2930500104.
    1. Choi HJ, Cho BC, Sohn JH, et al. Brain metastases from hepatocellular carcinoma: prognostic factors and outcome: brain metastasis from HCC. J Neurooncol. 2009;91:307–313. doi: 10.1007/s11060-008-9713-3.
    1. Nakamura N, Igaki H, Yamashita H, et al. A retrospective study of radiotherapy for spinal bone metastases from hepatocellular carcinoma (HCC) Jpn J Clin Oncol. 2007;37:38–43. doi: 10.1093/jjco/hyl128.
    1. Jiang W, Zeng ZC, Zhang JY, Fan J, Zeng MS, Zhou J. Palliative radiation therapy for pulmonary metastases from hepatocellular carcinoma. Clin Exp Metastasis. 2012;29:197–205. doi: 10.1007/s10585-011-9442-4.
    1. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–390. doi: 10.1056/NEJMoa0708857.
    1. Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34. doi: 10.1016/S1470-2045(08)70285-7.
    1. Cheng AL, Kang YK, Lin DY, et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol. 2013;31:4067–4075. doi: 10.1200/JCO.2012.45.8372.
    1. Johnson PJ, Qin S, Park JW, et al. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study. J Clin Oncol. 2013;31:3517–3524. doi: 10.1200/JCO.2012.48.4410.
    1. Cainap C, Qin S, Huang WT, et al. Phase III trial of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC) J Clin Oncol. 2013;31(Suppl 4) abstr 249.
    1. Furuse J, Ishii H, Nakachi K, Suzuki E, Shimizu S, Nakajima K. Phase I study of sorafenib in Japanese patients with hepatocellular carcinoma. Cancer Sci. 2008;99:159–165.
    1. Shim JH, Park JW, Choi JI, Park BJ, Kim CM. Practical efficacy of sorafenib monotherapy for advanced hepatocellular carcinoma patients in a Hepatitis B virus-endemic area. J Cancer Res Clin Oncol. 2009;135:617–625. doi: 10.1007/s00432-008-0496-x.
    1. Kim JE, Ryoo BY, Ryu MH, et al. Sorafenib for hepatocellular carcinoma according to Child-Pugh class of liver function. Cancer Chemother Pharmacol. 2011;68:1285–1290. doi: 10.1007/s00280-011-1616-x.
    1. Lencioni R, Kudo M, Ye SL, et al. GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib): second interim analysis. Int J Clin Pract. 2014;68:609–617. doi: 10.1111/ijcp.12352.
    1. Kim HY, Park JW, Joo J, et al. Worse outcome of sorafenib therapy associated with ascites and Child-Pugh score in advanced hepatocellular carcinoma. J Gastroenterol Hepatol. 2013;28:1756–1761. doi: 10.1111/jgh.12310.
    1. Brose MS, Frenette CT, Keefe SM, Stein SM. Management of sorafenib-related adverse events: a clinician’s perspective. Semin Oncol. 2014;41(Suppl 2):S1–S16. doi: 10.1053/j.seminoncol.2014.01.001.
    1. Park JW, Amarapurkar D, Chao Y, et al. Consensus recommendations and review by an International Expert Panel on Interventions in Hepatocellular Carcinoma (EPOIHCC) Liver Int. 2013;33:327–337. doi: 10.1111/liv.12083.
    1. Cheng AL, Amarapurkar D, Chao Y, et al. Re-evaluating transarterial chemoembolization for the treatment of hepatocellular carcinoma: consensus recommendations and review by an International Expert Panel. Liver Int. 2014;34:174–183. doi: 10.1111/liv.12314.
    1. Kim HY, Park JW, Joo J, et al. Severity and timing of progression predict refractoriness to transarterial chemoembolization in hepatocellular carcinoma. J Gastroenterol Hepatol. 2012;27:1051–1056. doi: 10.1111/j.1440-1746.2011.06963.x.
    1. Park JW, Koh YH, Kim HB, et al. Phase II study of concurrent transarterial chemoembolization and sorafenib in patients with unresectable hepatocellular carcinoma. J Hepatol. 2012;56:1336–1342. doi: 10.1016/j.jhep.2012.01.006.
    1. Lencioni R, Llovet JM, Han G, et al. Sorafenib or placebo in combination with transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEBDOX) for intermediate-stage hepatocellular carcinoma (HCC): phase II, randomized, double-blind SPACE trial. J Clin Oncol. 2012;30(Suppl 4) abstr LBA154.
    1. Brandi G, de Rosa F, Agostini V, et al. Metronomic capecitabine in advanced hepatocellular carcinoma patients: a phase II study. Oncologist. 2013;18:1256–1257. doi: 10.1634/theoncologist.2013-0093.
    1. Mir O, Coriat R, Boudou-Rouquette P, et al. Gemcitabine and oxaliplatin as second-line treatment in patients with hepatocellular carcinoma pre-treated with sorafenib. Med Oncol. 2012;29:2793–2799. doi: 10.1007/s12032-012-0208-x.
    1. Lee JE, Bae SH, Choi JY, Yoon SK, You YK, Lee MA. Epirubicin, cisplatin, 5-FU combination chemotherapy in sorafenib-refractory metastatic hepatocellular carcinoma. World J Gastroenterol. 2014;20:235–241. doi: 10.3748/wjg.v20.i1.235.
    1. Chlebowski RT, Brzechwa-Adjukiewicz A, Cowden A, Block JB, Tong M, Chan KK. Doxorubicin (75 mg/m2) for hepatocellular carcinoma: clinical and pharmacokinetic results. Cancer Treat Rep. 1984;68:487–491.
    1. Choi TK, Lee NW, Wong J. Chemotherapy for advanced hepatocellular carcinoma: adriamycin versus quadruple chemotherapy. Cancer. 1984;53:401–405. doi: 10.1002/1097-0142(19840201)53:3<401::AID-CNCR2820530306>;2-L.
    1. Sciarrino E, Simonetti RG, Le Moli S, Pagliaro L. Adriamycin treatment for hepatocellular carcinoma: experience with 109 patients. Cancer. 1985;56:2751–2755. doi: 10.1002/1097-0142(19851215)56:12<2751::AID-CNCR2820561205>;2-O.
    1. Tetef M, Doroshow J, Akman S, et al. 5-Fluorouracil and high-dose calcium leucovorin for hepatocellular carcinoma: a phase II trial. Cancer Invest. 1995;13:460–463. doi: 10.3109/07357909509024907.
    1. Yang TS, Lin YC, Chen JS, Wang HM, Wang CH. Phase II study of gemcitabine in patients with advanced hepatocellular carcinoma. Cancer. 2000;89:750–756. doi: 10.1002/1097-0142(20000815)89:4<750::AID-CNCR5>;2-R.
    1. Guan Z, Wang Y, Maoleekoonpairoj S, et al. Prospective randomised phase II study of gemcitabine at standard or fixed dose rate schedule in unresectable hepatocellular carcinoma. Br J Cancer. 2003;89:1865–1869. doi: 10.1038/sj.bjc.6601369.
    1. Yen Y, Lim DW, Chung V, et al. Phase II study of oxaliplatin in patients with unresectable, metastatic, or recurrent hepatocellular cancer: a California Cancer Consortium Trial. Am J Clin Oncol. 2008;31:317–322. doi: 10.1097/COC.0b013e318162f57d.
    1. Patt YZ, Hassan MM, Aguayo A, et al. Oral capecitabine for the treatment of hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma. Cancer. 2004;101:578–586. doi: 10.1002/cncr.20368.
    1. Boige V, Taïeb J, Hebbar M, et al. Irinotecan as first-line chemotherapy in patients with advanced hepatocellular carcinoma: a multicenter phase II study with dose adjustment according to baseline serum bilirubin level. Eur J Cancer. 2006;42:456–459. doi: 10.1016/j.ejca.2005.09.034.
    1. Yuen MF, Poon RT, Lai CL, et al. A randomized placebo-controlled study of long-acting octreotide for the treatment of advanced hepatocellular carcinoma. Hepatology. 2002;36:687–691. doi: 10.1053/jhep.2002.35071.
    1. Barbare JC, Bouché O, Bonnetain F, et al. Treatment of advanced hepatocellular carcinoma with long-acting octreotide: a phase III multicentre, randomised, double blind placebo-controlled study. Eur J Cancer. 2009;45:1788–1797. doi: 10.1016/j.ejca.2009.02.018.
    1. Llovet JM, Sala M, Castells L, et al. Randomized controlled trial of interferon treatment for advanced hepatocellular carcinoma. Hepatology. 2000;31:54–58. doi: 10.1002/hep.510310111.
    1. Barbare JC, Bouché O, Bonnetain F, et al. Randomized controlled trial of tamoxifen in advanced hepatocellular carcinoma. J Clin Oncol. 2005;23:4338–4346. doi: 10.1200/JCO.2005.05.470.
    1. Yeo W, Mok TS, Zee B, et al. A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. J Natl Cancer Inst. 2005;97:1532–1538. doi: 10.1093/jnci/dji315.
    1. Qin S, Bai Y, Lim HY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol. 2013;31:3501–3508. doi: 10.1200/JCO.2012.44.5643.
    1. Lee J, Park JO, Kim WS, et al. Phase II study of doxorubicin and cisplatin in patients with metastatic hepatocellular carcinoma. Cancer Chemother Pharmacol. 2004;54:385–390. doi: 10.1007/s00280-004-0837-7.
    1. Shim JH, Park JW, Nam BH, Lee WJ, Kim CM. Efficacy of combination chemotherapy with capecitabine plus cisplatin in patients with unresectable hepatocellular carcinoma. Cancer Chemother Pharmacol. 2009;63:459–467. doi: 10.1007/s00280-008-0759-x.
    1. Lee JO, Lee KW, Oh DY, et al. Combination chemotherapy with capecitabine and cisplatin for patients with metastatic hepatocellular carcinoma. Ann Oncol. 2009;20:1402–1407. doi: 10.1093/annonc/mdp010.
    1. Keam B, Oh DY, Lee SH, et al. A phase II study of 5-fluorouracil and cisplatin systemic chemotherapy for inoperable hepatocellular carcinoma with alpha fetoprotein as a predictive and prognostic marker. Mol Med Rep. 2008;1:415–422.
    1. Louafi S, Boige V, Ducreux M, et al. Gemcitabine plus oxaliplatin (GEMOX) in patients with advanced hepatocellular carcinoma (HCC): results of a phase II study. Cancer. 2007;109:1384–1390. doi: 10.1002/cncr.22532.
    1. Boige V, Raoul JL, Pignon JP, et al. Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03–03 trial. Br J Cancer. 2007;97:862–867.
    1. Thomas MB. Systemic therapy for hepatocellular carcinoma. Cancer J. 2008;14:123–127. doi: 10.1097/PPO.0b013e31816a6058.
    1. Terashima T, Yamashita T, Arai K, et al. Feasibility and efficacy of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma after sorafenib. Hepatol Res. 2014;44:1179–1185. doi: 10.1111/hepr.12266.
    1. Jeong SW, Jang JY, Lee JE, et al. The efficacy of hepatic arterial infusion chemotherapy as an alternative to sorafenib in advanced hepatocellular carcinoma. Asia Pac J Clin Oncol. 2012;8:164–171. doi: 10.1111/j.1743-7563.2012.01543.x.
    1. Lim TY, Cheong JY, Cho SW, et al. Effect of low dose 5-fluorouracil and cisplatin intra-arterial infusion chemotherapy in advanced hepatocellular carcinoma with decompensated cirrhosis. Korean J Hepatol. 2006;12:65–73.
    1. Woo HY, Bae SH, Park JY, et al. A randomized comparative study of high-dose and low-dose hepatic arterial infusion chemotherapy for intractable, advanced hepatocellular carcinoma. Cancer Chemother Pharmacol. 2010;65:373–382. doi: 10.1007/s00280-009-1126-2.
    1. Hamada A, Yamakado K, Nakatsuka A, Takaki H, Akeboshi M, Takeda K. Hepatic arterial infusion chemotherapy with use of an implanted port system in patients with advanced hepatocellular carcinoma: prognostic factors. J Vasc Interv Radiol. 2004;15:835–841. doi: 10.1097/01.RVI.0000128815.35555.0E.
    1. Ueshima K, Kudo M, Takita M, et al. Hepatic arterial infusion chemotherapy using low-dose 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma. Oncology. 2010;78(Suppl 1):148–153. doi: 10.1159/000315244.
    1. Takaki-Hamabe S, Yamasaki T, Saeki I, et al. Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: is the addition of subcutaneous interferon-alpha-2b beneficial? Hepatol Res. 2009;39:223–230. doi: 10.1111/j.1872-034X.2008.00458.x.
    1. Yamashita T, Arai K, Sunagozaka H, et al. Randomized, phase II study comparing interferon combined with hepatic arterial infusion of fluorouracil plus cisplatin and fluorouracil alone in patients with advanced hepatocellular carcinoma. Oncology. 2011;81:281–290. doi: 10.1159/000334439.
    1. Roayaie S, Blume IN, Thung SN, et al. A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology. 2009;137:850–855. doi: 10.1053/j.gastro.2009.06.003.
    1. Belghiti J, Panis Y, Farges O, Benhamou JP, Fekete F. Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis. Ann Surg. 1991;214:114–117. doi: 10.1097/00000658-199108000-00004.
    1. Chen X, Zhang B, Yin X, Ren Z, Qiu S, Zhou J. Lipiodolized transarterial chemoembolization in hepatocellular carcinoma patients after curative resection. J Cancer Res Clin Oncol. 2013;139:773–781. doi: 10.1007/s00432-012-1343-7.
    1. Lau WY, Leung TW, Ho SK, et al. Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial. Lancet. 1999;353:797–801. doi: 10.1016/S0140-6736(98)06475-7.
    1. Boucher E, Corbinais S, Rolland Y, et al. Adjuvant intra-arterial injection of iodine-131-labeled lipiodol after resection of hepatocellular carcinoma. Hepatology. 2003;38:1237–1241. doi: 10.1053/jhep.2003.50473.
    1. Takayama T, Sekine T, Makuuchi M, et al. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet. 2000;356:802–807. doi: 10.1016/S0140-6736(00)02654-4.
    1. Shi HY, Wang SN, Wang SC, Chuang SC, Chen CM, Lee KT. Preoperative transarterial chemoembolization and resection for hepatocellular carcinoma: a nationwide Taiwan database analysis of long-term outcome predictors. J Surg Oncol. 2014;109:487–493. doi: 10.1002/jso.23521.
    1. Yeo W, Lam KC, Zee B, et al. Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy. Ann Oncol. 2004;15:1661–1666. doi: 10.1093/annonc/mdh430.
    1. Nagamatsu H, Itano S, Nagaoka S, et al. Prophylactic lamivudine administration prevents exacerbation of liver damage in HBe antigen positive patients with hepatocellular carcinoma undergoing transhepatic arterial infusion chemotherapy. Am J Gastroenterol. 2004;99:2369–2375. doi: 10.1111/j.1572-0241.2004.40069.x.
    1. Lalazar G, Rund D, Shouval D. Screening, prevention and treatment of viral hepatitis B reactivation in patients with haematological malignancies. Br J Haematol. 2007;136:699–712. doi: 10.1111/j.1365-2141.2006.06465.x.
    1. Mindikoglu AL, Regev A, Schiff ER. Hepatitis B virus reactivation after cytotoxic chemotherapy: the disease and its prevention. Clin Gastroenterol Hepatol. 2006;4:1076–1081. doi: 10.1016/j.cgh.2006.05.027.
    1. Lau GK, He ML, Fong DY, et al. Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation. Hepatology. 2002;36:702–709. doi: 10.1053/jhep.2002.35068.
    1. Yeo W, Chan PK, Zhong S, et al. Frequency of hepatitis B virus reactivation in cancer patients undergoing cytotoxic chemotherapy: a prospective study of 626 patients with identification of risk factors. J Med Virol. 2000;62:299–307. doi: 10.1002/1096-9071(200011)62:3<299::AID-JMV1>;2-0.
    1. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507–539. doi: 10.1002/hep.21513.
    1. Wu XY, Li X, Chen ZH, et al. An optimized antiviral modification strategy for prevention of hepatitis B reactivation in patients undergoing prophylactic lamivudine and chemotherapy: a pilot study. Tumour Biol. 2013;34:909–918. doi: 10.1007/s13277-012-0626-6.
    1. Cortelezzi A, Viganò M, Zilioli VR, et al. Adefovir added to lamivudine for hepatitis B recurrent infection in refractory B-cell chronic lymphocytic leukemia on prolonged therapy with Campath-1H. J Clin Virol. 2006;35:467–469. doi: 10.1016/j.jcv.2005.10.009.
    1. Huang L, Li J, Yan J, et al. Antiviral therapy decreases viral reactivation in patients with hepatitis B virus-related hepatocellular carcinoma undergoing hepatectomy: a randomized controlled trial. J Viral Hepat. 2013;20:336–342. doi: 10.1111/jvh.12036.
    1. Huang G, Lai EC, Lau WY, et al. Posthepatectomy HBV reactivation in hepatitis B-related hepatocellular carcinoma influences postoperative survival in patients with preoperative low HBV-DNA levels. Ann Surg. 2013;257:490–505. doi: 10.1097/SLA.0b013e318262b218.
    1. Lao XM, Luo G, Ye LT, et al. Effects of antiviral therapy on hepatitis B virus reactivation and liver function after resection or chemoembolization for hepatocellular carcinoma. Liver Int. 2013;33:595–604. doi: 10.1111/liv.12112.
    1. Lao XM, Wang D, Shi M, et al. Changes in hepatitis B virus DNA levels and liver function after transcatheter arterial chemoembolization of hepatocellular carcinoma. Hepatol Res. 2011;41:553–563. doi: 10.1111/j.1872-034X.2011.00796.x.
    1. Firpi RJ, Nelson DR. Management of viral hepatitis in hematologic malignancies. Blood Rev. 2008;22:117–126. doi: 10.1016/j.blre.2008.02.001.
    1. Jang JW, Choi JY, Bae SH, et al. A randomized controlled study of preemptive lamivudine in patients receiving transarterial chemo-lipiodolization. Hepatology. 2006;43:233–240. doi: 10.1002/hep.21024.
    1. Park JW, Park KW, Cho SH, et al. Risk of hepatitis B exacerbation is low after transcatheter arterial chemoembolization therapy for patients with HBV-related hepatocellular carcinoma: report of a prospective study. Am J Gastroenterol. 2005;100:2194–2200. doi: 10.1111/j.1572-0241.2005.00232.x.
    1. Jang JW, Kwon JH, You CR, et al. Risk of HBV reactivation according to viral status and treatment intensity in patients with hepatocellular carcinoma. Antivir Ther. 2011;16:969–977. doi: 10.3851/IMP1840.
    1. Tamori A, Nishiguchi S, Tanaka M, et al. Lamivudine therapy for hepatitis B virus reactivation in a patient receiving intra-arterial chemotherapy for advanced hepatocellular carcinoma. Hepatol Res. 2003;26:77–80. doi: 10.1016/S1386-6346(03)00002-0.
    1. Nagamatsu H, Kumashiro R, Itano S, Matsugaki S, Sata M. Investigation of associating factors in exacerbation of liver damage after chemotherapy in patients with HBV-related HCC. Hepatol Res. 2003;26:293–301. doi: 10.1016/S1386-6346(03)00158-X.
    1. Kubo S, Nishiguchi S, Hamba H, et al. Reactivation of viral replication after liver resection in patients infected with hepatitis B virus. Ann Surg. 2001;233:139–145. doi: 10.1097/00000658-200101000-00020.
    1. Kim JH, Park JW, Kim TH, Koh DW, Lee WJ, Kim CM. Hepatitis B virus reactivation after three-dimensional conformal radiotherapy in patients with hepatitis B virus-related hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 2007;69:813–819. doi: 10.1016/j.ijrobp.2007.04.005.
    1. Dan JQ, Zhang YJ, Huang JT, et al. Hepatitis B virus reactivation after radiofrequency ablation or hepatic resection for HBV-related small hepatocellular carcinoma: a retrospective study. Eur J Surg Oncol. 2013;39:865–872. doi: 10.1016/j.ejso.2013.03.020.
    1. Yoshida H, Yoshida H, Goto E, et al. Safety and efficacy of lamivudine after radiofrequency ablation in patients with hepatitis B virus-related hepatocellular carcinoma. Hepatol Int. 2008;2:89–94. doi: 10.1007/s12072-007-9020-7.
    1. Sung PS, Bae SH, Jang JW, et al. Differences in the patterns and outcomes of enhanced viral replication between hepatitis C virus and hepatitis B virus in patients with hepatocellular carcinoma during transarterial chemolipiodolization. Korean J Hepatol. 2011;17:299–306. doi: 10.3350/kjhep.2011.17.4.299.
    1. Hong SH, Roh SY, Kim SY, et al. Change in cancer pain management in Korea between 2001 and 2006: results of two nationwide surveys. J Pain Symptom Manage. 2011;41:93–103. doi: 10.1016/j.jpainsymman.2010.03.025.
    1. Kim JY, Jang WY, Hur MH, et al. Prevalence and management of pain by different age groups of Korean cancer patients. Am J Hosp Palliat Care. 2013;30:393–398. doi: 10.1177/1049909112452624.
    1. van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007;18:1437–1449. doi: 10.1093/annonc/mdm056.
    1. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363:733–742. doi: 10.1056/NEJMoa1000678.
    1. Carr BI, Pujol L. Pain at presentation and survival in hepatocellular carcinoma. J Pain. 2010;11:988–993. doi: 10.1016/j.jpain.2010.01.265.
    1. Ryu E, Kim K, Cho MS, Kwon IG, Kim HS, Fu MR. Symptom clusters and quality of life in Korean patients with hepatocellular carcinoma. Cancer Nurs. 2010;33:3–10. doi: 10.1097/NCC.0b013e3181b4367e.
    1. Verbeeck RK. Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur J Clin Pharmacol. 2008;64:1147–1161. doi: 10.1007/s00228-008-0553-z.
    1. Radner H, Ramiro S, Buchbinder R, Landewé RB, van der Heijde D, Aletaha D. Pain management for inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and other spondylarthritis) and gastrointestinal or liver comorbidity. Cochrane Database Syst Rev. 2012;1:CD008951.
    1. World Health Organization. Cancer pain relief. 2nd ed. Geneva: World Health Organization; 1996.
    1. Ministry of Health & Welfare. Cancer pain management guideline. 5th ed. Seoul: Ministry of Health & Welfare; 2012.
    1. National Comprehensive Cancer Network. NCCN clinical practice guideline in oncology: adult cancer pain. Vol. 1. Fort Washington: National Comprehensive Cancer Network; 2013.
    1. Rossi S, Assis DN, Awsare M, et al. Use of over-the-counter analgesics in patients with chronic liver disease: physicians’ recommendations. Drug Saf. 2008;31:261–270. doi: 10.2165/00002018-200831030-00007.
    1. Larson AM, Polson J, Fontana RJ, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42:1364–1372. doi: 10.1002/hep.20948.
    1. U.S. Department of Health and Human Services; U.S. Food and Drug Administration. Drugs: acetaminophen information [Internet] Silver Spring: U.S. Food and Drug Administration; 2013. [cited 2013 Jan 15]. Available from: .
    1. Mofredj A, Cadranel JF, Darchy B, et al. Hepatotoxicity caused by therapeutic doses of paracetamol in alcoholics: report of 2 cases of fatal hepatitis in cirrhosis. Ann Med Interne (Paris) 1999;150:507–511.
    1. Dart RC, Bailey E. Does therapeutic use of acetaminophen cause acute liver failure? Pharmacotherapy. 2007;27:1219–1230. doi: 10.1592/phco.27.9.1219.
    1. Kuffner EK, Green JL, Bogdan GM, et al. The effect of acetaminophen (four grams a day for three consecutive days) on hepatic tests in alcoholic patients: a multicenter randomized study. BMC Med. 2007;5:13. doi: 10.1186/1741-7015-5-13.
    1. Heard K, Green JL, Bailey JE, Bogdan GM, Dart RC. A randomized trial to determine the change in alanine aminotransferase during 10 days of paracetamol (acetaminophen) administration in subjects who consume moderate amounts of alcohol. Aliment Pharmacol Ther. 2007;26:283–290. doi: 10.1111/j.1365-2036.2007.03368.x.
    1. Khalid SK, Lane J, Navarro V, Garcia-Tsao G. Use of over-the-counter analgesics is not associated with acute decompensation in patients with cirrhosis. Clin Gastroenterol Hepatol. 2009;7:994–999. doi: 10.1016/j.cgh.2009.04.015.
    1. Villeneuve JP, Raymond G, Bruneau J, Colpron L, Pomier-Layrargues G. Pharmacokinetics and metabolism of acetaminophen in normal, alcoholic and cirrhotic subjects. Gastroenterol Clin Biol. 1983;7:898–902.
    1. Hirschfield GM, Kumagi T, Heathcote EJ. Preventative hepatology: minimising symptoms and optimising care. Liver Int. 2008;28:922–934. doi: 10.1111/j.1478-3231.2008.01816.x.
    1. Benson GD, Koff RS, Tolman KG. The therapeutic use of acetaminophen in patients with liver disease. Am J Ther. 2005;12:133–141. doi: 10.1097/01.mjt.0000140216.40700.95.
    1. Chandok N, Watt KD. Pain management in the cirrhotic patient: the clinical challenge. Mayo Clin Proc. 2010;85:451–458. doi: 10.4065/mcp.2009.0534.
    1. Williams RL, Upton RA, Cello JP, et al. Naproxen disposition in patients with alcoholic cirrhosis. Eur J Clin Pharmacol. 1984;27:291–296. doi: 10.1007/BF00542162.
    1. Bessone F. Non-steroidal anti-inflammatory drugs: what is the actual risk of liver damage? World J Gastroenterol. 2010;16:5651–5661. doi: 10.3748/wjg.v16.i45.5651.
    1. Riley TR, 3rd, Smith JP. Ibuprofen-induced hepatotoxicity in patients with chronic hepatitis C: a case series. Am J Gastroenterol. 1998;93:1563–1565. doi: 10.1111/j.1572-0241.1998.00484.x.
    1. Ackerman Z, Cominelli F, Reynolds TB. Effect of misoprostol on ibuprofen-induced renal dysfunction in patients with decompensated cirrhosis: results of a double-blind placebo-controlled parallel group study. Am J Gastroenterol. 2002;97:2033–2039. doi: 10.1111/j.1572-0241.2002.05847.x.
    1. Castro-Fernández M1, Sánchez-Muñoz D, Galán-Jurado MV, et al. Influence of nonsteroidal antiinflammatory drugs in gastrointestinal bleeding due to gastroduodenal ulcers or erosions in patients with liver cirrhosis. Gastroenterol Hepatol. 2006;29:11–14. doi: 10.1157/13083251.
    1. Lee YC, Chang CH, Lin JW, Chen HC, Lin MS, Lai MS. Non-steroidal anti-inflammatory drugs use and risk of upper gastrointestinal adverse events in cirrhotic patients. Liver Int. 2012;32:859–866. doi: 10.1111/j.1478-3231.2011.02739.x.
    1. Smith HS. Opioid metabolism. Mayo Clin Proc. 2009;84:613–624. doi: 10.1016/S0025-6196(11)60750-7.
    1. Hasselström J, Eriksson S, Persson A, Rane A, Svensson JO, Säwe J. The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. Br J Clin Pharmacol. 1990;29:289–297. doi: 10.1111/j.1365-2125.1990.tb03638.x.
    1. Tegeder I, Lötsch J, Geisslinger G. Pharmacokinetics of opioids in liver disease. Clin Pharmacokinet. 1999;37:17–40. doi: 10.2165/00003088-199937010-00002.
    1. Kotb HI, El-Kady SA, Emara SE, Fouad EA, El-Kabsh MY. Pharmacokinetics of controlled release morphine (MST) in patients with liver carcinoma. Br J Anaesth. 2005;94:95–99. doi: 10.1093/bja/aei007.
    1. Kotb HI, Fouad IA, Fares KM, Mostafa MG, Abd El-Rahman AM. Pharmacokinetics of oral tramadol in patients with liver cancer. J Opioid Manag. 2008;4:99–104.
    1. Tallgren M, Olkkola KT, Seppälä T, Höckerstedt K, Lindgren L. Pharmacokinetics and ventilatory effects of oxycodone before and after liver transplantation. Clin Pharmacol Ther. 1997;61:655–661. doi: 10.1016/S0009-9236(97)90100-4.
    1. Durnin C, Hind ID, Ghani SP, Yates DB, Molz KH. Pharmacokinetics of oral immediate-release hydromorphone (Dilaudid IR) in subjects with moderate hepatic impairment. Proc West Pharmacol Soc. 2001;44:83–84.
    1. Haberer JP, Schoeffler P, Couderc E, Duvaldestin P. Fentanyl pharmacokinetics in anaesthetized patients with cirrhosis. Br J Anaesth. 1982;54:1267–1270. doi: 10.1093/bja/54.12.1267.
    1. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47:207–214. doi: 10.1002/1097-0142(19810101)47:1<207::AID-CNCR2820470134>;2-6.
    1. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–216. doi: 10.1093/jnci/92.3.205.
    1. Bogaerts J, Ford R, Sargent D, et al. Individual patient data analysis to assess modifications to the RECIST criteria. Eur J Cancer. 2009;45:248–260. doi: 10.1016/j.ejca.2008.10.027.
    1. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45:228–247. doi: 10.1016/j.ejca.2008.10.026.
    1. Forner A, Ayuso C, Varela M, et al. Evaluation of tumor response after locoregional therapies in hepatocellular carcinoma: are response evaluation criteria in solid tumors reliable? Cancer. 2009;115:616–623. doi: 10.1002/cncr.24050.
    1. Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma: conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001;35:421–430. doi: 10.1016/S0168-8278(01)00130-1.
    1. Llovet JM, Di Bisceglie AM, Bruix J, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008;100:698–711. doi: 10.1093/jnci/djn134.
    1. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60. doi: 10.1055/s-0030-1247132.
    1. Okada S, Shimada K, Yamamoto J, et al. Predictive factors for postoperative recurrence of hepatocellular carcinoma. Gastroenterology. 1994;106:1618–1624.
    1. Shirabe K, Kanematsu T, Matsumata T, Adachi E, Akazawa K, Sugimachi K. Factors linked to early recurrence of small hepatocellular carcinoma after hepatectomy: univariate and multivariate analyses. Hepatology. 1991;14:802–805. doi: 10.1002/hep.1840140510.
    1. Poon RT, Fan ST, Lo CM, Liu CL, Wong J. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg. 1999;229:216–222. doi: 10.1097/00000658-199902000-00009.
    1. Adachi E, Maeda T, Matsumata T, et al. Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma. Gastroenterology. 1995;108:768–775. doi: 10.1016/0016-5085(95)90450-6.
    1. Kim BK, Park JY, Kim do Y, et al. Persistent hepatitis B viral replication affects recurrence of hepatocellular carcinoma after curative resection. Liver Int. 2008;28:393–401. doi: 10.1111/j.1478-3231.2007.01625.x.
    1. Ohkubo K, Kato Y, Ichikawa T, et al. Viral load is a significant prognostic factor for hepatitis B virus-associated hepatocellular carcinoma. Cancer. 2002;94:2663–2668. doi: 10.1002/cncr.10557.
    1. Hung IF, Poon RT, Lai CL, Fung J, Fan ST, Yuen MF. Recurrence of hepatitis B-related hepatocellular carcinoma is associated with high viral load at the time of resection. Am J Gastroenterol. 2008;103:1663–1673. doi: 10.1111/j.1572-0241.2008.01872.x.
    1. Kubo S, Nishiguchi S, Hirohashi K, et al. Clinicopathological criteria for multicentricity of hepatocellular carcinoma and risk factors for such carcinogenesis. Jpn J Cancer Res. 1998;89:419–426. doi: 10.1111/j.1349-7006.1998.tb00580.x.
    1. Kubo S, Yamamoto T, Ikebe T, et al. Relationship between multicentric occurrence of hepatocellular carcinoma and histology of noncancerous hepatic tissue in patients with chronic hepatitis C. Jpn J Cancer Res. 1999;90:1076–1080. doi: 10.1111/j.1349-7006.1999.tb00680.x.
    1. Todo S, Furukawa H. Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan. Ann Surg. 2004;240:451–459. doi: 10.1097/01.sla.0000137129.98894.42.
    1. Shetty K, Timmins K, Brensinger C, et al. Liver transplantation for hepatocellular carcinoma validation of present selection criteria in predicting outcome. Liver Transpl. 2004;10:911–918. doi: 10.1002/lt.20140.
    1. Löhe F, Angele MK, Gerbes AL, Löhrs U, Jauch KW, Schauer RJ. Tumour size is an important predictor for the outcome after liver transplantation for hepatocellular carcinoma. Eur J Surg Oncol. 2005;31:994–999. doi: 10.1016/j.ejso.2005.06.003.
    1. Park MS, Lee KW, Suh SW, et al. Living-donor liver transplantation associated with higher incidence of hepatocellular carcinoma recurrence than deceased-donor liver transplantation. Transplantation. 2014;97:71–77. doi: 10.1097/TP.0b013e3182a68953.
    1. Pompili M, Saviano A, de Matthaeis N, et al. Long-term effectiveness of resection and radiofrequency ablation for single hepatocellular carcinoma </=3 cm: results of a multicenter Italian survey. J Hepatol. 2013;59:89–97. doi: 10.1016/j.jhep.2013.03.009.
    1. Hasegawa K, Kokudo N, Makuuchi M, et al. Comparison of resection and ablation for hepatocellular carcinoma: a cohort study based on a Japanese nationwide survey. J Hepatol. 2013;58:724–729. doi: 10.1016/j.jhep.2012.11.009.
    1. Khan KN, Yatsuhashi H, Yamasaki K, et al. Prospective analysis of risk factors for early intrahepatic recurrence of hepatocellular carcinoma following ethanol injection. J Hepatol. 2000;32:269–278. doi: 10.1016/S0168-8278(00)80072-0.
    1. Rossi S, Ravetta V, Rosa L, et al. Repeated radiofrequency ablation for management of patients with cirrhosis with small hepatocellular carcinomas: a long-term cohort study. Hepatology. 2011;53:136–147. doi: 10.1002/hep.23965.
    1. Yang JD, Kim WR, Park KW, et al. Model to estimate survival in ambulatory patients with hepatocellular carcinoma. Hepatology. 2012;56:614–621. doi: 10.1002/hep.25680.
    1. Kim BH, Park JW, Nam BH, Kwak HW, Kim WR. Validation of a model to estimate survival in ambulatory patients with hepatocellular carcinoma: a single-centre cohort study. Liver Int. 2014;34:e317–e323. doi: 10.1111/liv.12519.

Source: PubMed

3
Předplatit