803
Views
39
CrossRef citations to date
0
Altmetric
Review

Postoperative therapy options for hepatocellular carcinoma

, &
Pages 649-661 | Received 29 Nov 2013, Accepted 14 Mar 2014, Published online: 10 Apr 2014

References

  • Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11–30.
  • Bolondi L, Sofia S, Siringo S, Gaiani S, Casali A, Zironi G, et al. Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis. Gut 2001;48:251–9.
  • Zhong JH, Ke Y, Gong WF, Xiang BD, Ma L, Ye XP, et al. Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma. Ann Surg 2013; In press.
  • Zhong JH, Xiang BD, Gong WF, Ke Y, Mo QG, Ma L, et al. Comparison of long-term survival of patients with BCLC stage B hepatocellular carcinoma after liver resection or transarterial chemoembolization. PLoS One 2013;8:e68193.
  • Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907–17.
  • Poon D, Anderson BO, Chen LT, Tanaka K, Lau WY, Van Cutsem E, et al. Management of hepatocellular carcinoma in Asia: consensus statement from the Asian Oncology Summit 2009. Lancet Oncol 2009;10:1111–18.
  • de Lope CR, Tremosini S, Forner A, Reig M, Bruix J. Management of HCC. J Hepatol 2012;56:S75–87.
  • Verslype C, Rosmorduc O, Rougier P. Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23:vii41–8.
  • Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet 2012;379:1245–55.
  • 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;56:908–43.
  • Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005;42:1208–36.
  • Omata M, Lesmana LA, Tateishi R, Chen PJ, Lin SM, Yoshida H, et al. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 2010;4:439–74.
  • Chen LT, Chen MF, Li LA, Lee PH, Jeng LB, Lin DY, 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.
  • Ikeda K, Arase Y, Saitoh S, Kobayashi M, Suzuki Y, Suzuki F, et al. Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor-A prospective randomized study of hepatitis C virus-related liver cancer. Hepatology 2000;32:228–32.
  • Kubo S, Nishiguchi S, Hirohashi K, Tanaka H, Shuto T, Kinoshita H. Randomized clinical trial of long-term outcome after resection of hepatitis C virus-related hepatocellular carcinoma by postoperative interferon therapy. Br J Surg 2002;89:418–22.
  • Lin SM, Lin CJ, Hsu CW, Tai DI, Sheen IS, Lin DY, et al. Prospective randomized controlled study of interferon-alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors. Cancer 2004;100:376–82.
  • Lo CM, Liu CL, Chan SC, Lam CM, Poon RT, Ng IO, et al. A randomized, controlled trial of postoperative adjuvant interferon therapy after resection of hepatocellular carcinoma. Ann Surg 2007;245:831–42.
  • Shiratori Y, Shiina S, Teratani T, Imamura M, Obi S, Sato S, 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.
  • Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH, et al. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol 2006;132:458–65.
  • Mazzaferro V, Romito R, Schiavo M, Mariani L, Camerini T, Bhoori S, et al. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology 2006;44:1543–54.
  • Breitenstein S, Dimitroulis D, Petrowsky H, Puhan MA, Mullhaupt B, Clavien PA. Systematic review and meta-analysis of interferon after curative treatment of hepatocellular carcinoma in patients with viral hepatitis. Br J Surg 2009;96:975–81.
  • Huang TS, Shyu YC, Chen HY, Yuan SS, Shih JN, Chen PJ. A systematic review and meta-analysis of adjuvant interferon therapy after curative treatment for patients with viral hepatitis-related hepatocellular carcinoma. J Viral Hepat 2013;20:729–43.
  • Miao RY, Zhao HT, Yang HY, Mao YL, Lu X, Zhao Y, et al. Postoperative adjuvant antiviral therapy for hepatitis B/C virus-related hepatocellular carcinoma: a meta-analysis. World J Gastroenterol 2010;16:2931–42.
  • Miyake Y, Takaki A, Iwasaki Y, Yamamoto K. Meta-analysis: interferon-alpha prevents the recurrence after curative treatment of hepatitis C virus-related hepatocellular carcinoma. J Viral Hepat 2010;17:287–92.
  • Shen YC, Hsu C, Chen LT, Cheng CC, Hu FC, Cheng AL. Adjuvant interferon therapy after curative therapy for hepatocellular carcinoma (HCC): a meta-regression approach. J Hepatol 2010;52:889–94.
  • Singal AK, Freeman DH Jr, Anand BS. Meta-analysis: interferon improves outcomes following ablation or resection of hepatocellular carcinoma. Aliment Pharmacol Ther 2010;32:851–8.
  • Xu JB, Qi FZ, Xu G, Chen GF, Huang MD, Zhang JH. Adjuvant interferon therapy after surgical treatment for hepatitis B/C virus-related hepatocellular carcinoma: a meta-analysis. Hepatol Res 2014;44:209–17.
  • Zhang CH, Xu GL, Jia WD, Ge YS. Effects of interferon alpha treatment on recurrence and survival after complete resection or ablation of hepatocellular carcinoma: a meta-analysis of randomized controlled trials. Int J Cancer 2009;124:2982–8.
  • Zhong JH, Li H, Li LQ, You XM, Zhang Y, Zhao YN, et al. Adjuvant therapy options following curative treatment of hepatocellular carcinoma: a systematic review of randomized trials. Eur J Surg Oncol 2012;38:286–95.
  • Wang J, He XD, Yao N, Liang WJ, Zhang YC. A meta-analysis of adjuvant therapy after potentially curative treatment for hepatocellular carcinoma. Can J Gastroenterol 2013;27:351–63.
  • Jiang S, Liu Y, Wang L, Duan C, Liu M. A meta-analysis and systematic review: adjuvant interferon therapy for patients with viral hepatitis-related hepatocellular carcinoma. World J Surg Oncol 2013;11:240.
  • Zhang CH, Xu GL, Jia WD, Li JS, Ma JL, Ge YS. Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: a meta-analysis of randomized controlled trials. Int J Cancer 2011;129:1254–64.
  • Yamazhan T, Kurtaran B, Pullukçu H, Yüksel E, Ozkaya D, Taşbakan MI, et al. Pegylated interferon in HBeAg-positive and-negative chronic hepatitis B patients: post-treatment 1-year results of three Turkish centres. J Chemother 2013; In press.
  • Ormeci N. Short- and long-term effects of treatment of chronic hepatitis B and delta virus by IFN. Fundam Clin Pharmacol 2003;17:651–8.
  • Damdinsuren B, Nagano H, Wada H, Kondo M, Ota H, Nakamura M, et al. Stronger growth-inhibitory effect of interferon (IFN)-beta compared to IFN-alpha is mediated by IFN signaling pathway in hepatocellular carcinoma cells. Int J Oncol 2007;30:201–8.
  • Yamaji K, Nabeshima S, Murata M, Chong Y, Furusyo N, Ikematsu H, et al. Interferon-alpha/beta upregulate IL-15 expression in vitro and in vivo: analysis in human hepatocellular carcinoma cell lines and in chronic hepatitis C patients during interferon-alpha/beta treatment. Cancer Immunol Immunother 2006;55:394–403.
  • Murata M, Nabeshima S, Kikuchi K, Yamaji K, Furusyo N, Hayashi J. A comparison of the antitumor effects of interferon-alpha and beta on human hepatocellular carcinoma cell lines. Cytokine 2006;33:121–8.
  • Yamamoto T, Nakamura H, Liu W, Cao K, Yoshikawa S, Enomoto H, et al. Involvement of hepatoma-derived growth factor in the growth inhibition of hepatocellular carcinoma cells by vitamin K(2). J Gastroenterol 2009;44:228–35.
  • Yoshida H, Shiratori Y, Kudo M, Shiina S, Mizuta T, Kojiro M, et al. Effect of vitamin K2 on the recurrence of hepatocellular carcinoma. Hepatology 2011;54:532–40.
  • Hotta N, Ayada M, Sato K, Ishikawa T, Okumura A, Matsumoto E, et al. Effect of vitamin K2 on the recurrence in patients with hepatocellular carcinoma. Hepatogastroenterology 2007;54:2073–7.
  • Ishizuka M, Kubota K, Shimoda M, Kita J, Kato M, Park KH, et al. Effect of menatetrenone, a vitamin k2 analog, on recurrence of hepatocellular carcinoma after surgical resection: a prospective randomized controlled trial. Anticancer Res 2012;32:5415–20.
  • Kakizaki S, Sohara N, Sato K, Suzuki H, Yanagisawa M, Nakajima H, et al. Preventive effects of vitamin K on recurrent disease in patients with hepatocellular carcinoma arising from hepatitis C viral infection. J Gastroenterol Hepatol 2007;22:518–22.
  • Mizuta T, Ozaki I, Eguchi Y, Yasutake T, Kawazoe S, Fujimoto K, et al. The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment: a pilot study. Cancer 2006;106:867–72.
  • Yoshiji H, Noguchi R, Toyohara M, Ikenaka Y, Kitade M, Kaji K, et al. Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma. J Hepatol 2009;51:315–21.
  • Zhong JH, Mo XS, Xiang BD, Yuan WP, Jiang JF, Xie GS, et al. Postoperative use of the chemopreventive vitamin K2 analog in patients with hepatocellular carcinoma. PLoS One 2013;8:e58082.
  • Riaz IB, Riaz H, Riaz T, Rahman S, Amir M, Badshah MB, et al. Role of vitamin K2 in preventing the recurrence of hepatocellular carcinoma after curative treatment: a meta-analysis of randomized controlled trials. BMC Gastroenterol 2012;12:170.
  • Chu KJ, Lai EC, Yao XP, Zhang HW, Lau WY, Fu XH, et al. Vitamin analogues in chemoprevention of hepatocellular carcinoma after resection or ablation–a systematic review and meta-analysis. Asian J Surg 2010;33:120–6.
  • Zhong JH, Gong WF, Li LQ, You XM, Ma L, Xiang BD, Peng NF. Meta-analysis of postoperative chemopreventive Vitamin K2 analog for patients with hepatocellular carcinoma. J Gastroenterol Hepatol 2012;27:212–13.
  • Muto Y, Moriwaki H, Ninomiya M, Adachi S, Saito A, Takasaki KT, et al. Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group. N Engl J Med 1996;334:1561–7.
  • Takai K, Okuno M, Yasuda I, Matsushima-Nishiwaki R, Uematsu T, Tsurumi H, et al. Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma. Updated analysis of the long-term follow-up data. Intervirology 2005;48:39–45.
  • Muto Y, Moriwaki H, Saito A. Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma. N Engl J Med 1999;340:1046–7.
  • Zhong JH, Li LQ. Postoperative adjuvant transarterial chemoembolization for participants with hepatocellular carcinoma: a meta-analysis. Hepatol Res 2010;40:943–53.
  • Izumi R, Shimizu K, Iyobe T, Ii T, Yagi M, Matsui O, et al. Postoperative adjuvant hepatic arterial infusion of Lipiodol containing anticancer drugs in patients with hepatocellular carcinoma. Hepatology 1994;20:295–301.
  • Li JQ, Zhang YQ, Zhang WZ, Yuan YF, Li GH. Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy. J Cancer Res Clin Oncol 1995;121:364–6.
  • Li Q, Wang J, Sun Y, Cui YL, Juzi JT, Qian BY, et al. Postoperative transhepatic arterial chemoembolization and portal vein chemotherapy for patients with hepatocellular carcinoma: a randomized study with 131 cases. Dig Surg 2006;23:235–40.
  • Peng BG, He Q, Li JP, Zhou F. Adjuvant transcatheter arterial chemoembolization improves efficacy of hepatectomy for patients with hepatocellular carcinoma and portal vein tumor thrombus. Am J Surg 2009;198:313–18.
  • Zhong C, Guo RP, Li JQ, Shi M, Wei W, Chen MS, et al. A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage III A hepatocellular carcinoma. J Cancer Res Clin Oncol 2009;135:1437–45.
  • Kwok PC, Lam TW, Lam PW, Tang KW, Chan SC, Hwang JS, et al. Randomized controlled trial to compare the dose of adjuvant chemotherapy after curative resection of hepatocellular carcinoma. J Gastroenterol Hepatol 2003;18:450–5.
  • Schwartz JD, Schwartz M, Mandeli J, Sung M. Neoadjuvant and adjuvant therapy for resectable hepatocellular carcinoma: review of the randomised clinical trials. Lancet Oncol 2002;3:593–603.
  • Mathurin P, Raynard B, Dharancy S, Kirzin S, Fallik D, Pruvot FR, et al. Meta-analysis: evaluation of adjuvant therapy after curative liver resection for hepatocellular carcinoma. Aliment Pharmacol Ther 2003;17:1247–61.
  • Sun HC, Tang ZY. Preventive treatments for recurrence after curative resection of hepatocellular carcinoma–a literature review of randomized control trials. World J Gastroenterol 2003;9:635–40.
  • Samuel M, Chow PK, Chan Shih-Yen E, Machin D, Soo KC. Neoadjuvant and adjuvant therapy for surgical resection of hepatocellular carcinoma. Cochrane Database Syst Rev 2009:CD001199.
  • Lau WY, Lai EC, Lau SH. The current role of neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for hepatocellular carcinoma: a systematic review. Hepatobiliary Pancreat Dis Int 2009;8:124–33.
  • Lai EC, Lo CM, Fan ST, Liu CL, Wong J. Postoperative adjuvant chemotherapy after curative resection of hepatocellular carcinoma: a randomized controlled trial. Arch Surg 1998;133:183–8.
  • Kohno H, Nagasue N, Hayashi T, Yamanoi A, Uchida M, Ono T, et al. Postoperative adjuvant chemotherapy after radical hepatic resection for hepatocellular carcinoma (HCC). Hepatogastroenterology 1996;43:1405–9.
  • Ono T, Nagasue N, Kohno H, Hayashi T, Uchida M, Yukaya H, et al. Adjuvant chemotherapy with epirubicin and carmofur after radical resection of hepatocellular carcinoma: a prospective randomized study. Semin Oncol 1997;24:S6–18; S16-25.
  • Ono T, Yamanoi A, Nazmy El Assal O, Kohno H, Nagasue N. Adjuvant chemotherapy after resection of hepatocellular carcinoma causes deterioration of long-term prognosis in cirrhotic patients: metaanalysis of three randomized controlled trials. Cancer 2001;91:2378–85.
  • Lau WY, Leung TW, Ho SK, Chan M, Machin D, Lau J, et al. Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial. Lancet 1999;353:797–801.
  • Lau WY, Lai EC, Leung TW, Yu SC. Adjuvant intra-arterial iodine-131-labeled lipiodol for resectable hepatocellular carcinoma: a prospective randomized trial-update on 5-year and 10-year survival. Ann Surg 2008;247:43–8.
  • Chung AY, Ooi LL, Machin D, Tan SB, Goh BK, Wong JS, et al. Adjuvant hepatic intra-arterial iodine-131-lipiodol following curative resection of hepatocellular carcinoma: a prospective randomized trial. World J Surg 2013;37:1356–61.
  • Yamamoto M, Arii S, Sugahara K, Tobe T. Adjuvant oral chemotherapy to prevent recurrence after curative resection for hepatocellular carcinoma. Br J Surg 1996;83:336–40.
  • Hasegawa K, Takayama T, Ijichi M, Matsuyama Y, Imamura H, Sano K, et al. Uracil-tegafur as an adjuvant for hepatocellular carcinoma: a randomized trial. Hepatology 2006;44:891–5.
  • Xia Y, Qiu Y, Li J, Shi L, Wang K, Xi T, et al. Adjuvant therapy with capecitabine postpones recurrence of hepatocellular carcinoma after curative resection: a randomized controlled trial. Ann Surg Oncol 2010;17:3137–44.
  • Zhong JH, Li LQ. Conventional oral systemic chemotherapy for postoperative hepatocellular carcinoma. J Canc Res Updates 2014;3:11–18.
  • Takayama T, Sekine T, Makuuchi M, Yamasaki S, Kosuge T, Yamamoto J, et al. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet 2000;356:802–7.
  • Hui D, Qiang L, Jian W, Ti Z, Da-Lu K. A randomized, controlled trial of postoperative adjuvant cytokine-induced killer cells immunotherapy after radical resection of hepatocellular carcinoma. Dig Liver Dis 2009;41:36–41.
  • Weng DS, Zhou J, Zhou QM, Zhao M, Wang QJ, Huang LX, et al. Minimally invasive treatment combined with cytokine-induced killer cells therapy lower the short-term recurrence rates of hepatocellular carcinomas. J Immunother 2008;31:63–71.
  • Zhong JH, Ma L, Wu LC, Zhao W, Yuan WP, Wu FX, et al. Adoptive immunotherapy for postoperative hepatocellular carcinoma: a systematic review. Int J Clin Pract 2012;66:21–7.
  • Xie F, Zhang X, Li H, Zheng T, Xu F, Shen R, et al. Adoptive immunotherapy in postoperative hepatocellular carcinoma: a systemic review. PLoS One 2012;7:e42879.
  • Kuang M, Peng BG, Lu MD, Liang LJ, Huang JF, He Q, et al. Phase II randomized trial of autologous formalin-fixed tumor vaccine for postsurgical recurrence of hepatocellular carcinoma. Clin Cancer Res 2004;10:1574–9.
  • Kawata A, Une Y, Hosokawa M, Wakizaka Y, Namieno T, Uchino J, et al. Adjuvant chemoimmunotherapy for hepatocellular carcinoma patients. Adriamycin, interleukin-2, and lymphokine-activated killer cells versus adriamycin alone. Am J Clin Oncol 1995;18:257–62.
  • Yang YF, Zhao W, Zhong YD, Xia HM, Shen L, Zhang N. Interferon therapy in chronic hepatitis B reduces progression to cirrhosis and hepatocellular carcinoma: a meta-analysis. J Viral Hepat 2009;16:265–71.
  • Singal AK, Salameh H, Kuo YF, Fontana RJ. Meta-analysis: the impact of oral anti-viral agents on the incidence of hepatocellular carcinoma in chronic hepatitis B. Aliment Pharmacol Ther 2013;38:98–106.
  • Kubo S, Hirohashi K, Tanaka H, Tsukamoto T, Shuto T, Yamamoto T, et al. Effect of viral status on recurrence after liver resection for patients with hepatitis B virus-related hepatocellular carcinoma. Cancer 2000;88:1016–24.
  • Wu JC, Huang YH, Chau GY, Su CW, Lai CR, Lee PC, et al. Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma. J Hepatol 2009;51:890–7.
  • Yin J, Li N, Han Y, Xue J, Deng Y, Shi J, 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;31:3647–55.
  • Wong JS, Wong GL, Tsoi KK, Wong VW, Cheung SY, Chong CN, 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;33:1104–12.
  • Ke Y, Ma L, You XM, Huang SX, Liang YR, Xiang BD, et al. Antiviral therapy for hepatitis B virus-related hepatocellular carcinoma after radical hepatectomy. Cancer Biol Med 2013;10:158–64.
  • Zhong JH, Li LQ, Wu LC. Lamivudine with or without adefovir dipivoxil for postoperative hepatocellular carcinoma. Cochrane Database Syst Rev 2011:CD008713.
  • The SAN-IN Group of Liver Surgery. Long-term oral administration of branched chain amino acids after curative resection of hepatocellular carcinoma: a prospective randomized trial. The San-in Group of Liver Surgery. Br J Surg 1997;84:1525–31.
  • Meng WC, Leung KL, Ho RL, Leung TW, Lau WY. Prospective randomized control study on the effect of branched-chain amino acids in patients with liver resection for hepatocellular carcinoma. Aust N Z J Surg 1999;69:811–15.
  • Okabayashi T, Iyoki M, Sugimoto T, Kobayashi M, Hanazaki K. Oral supplementation with carbohydrate- and branched-chain amino acid-enriched nutrients improves postoperative quality of life in patients undergoing hepatic resection. Amino Acids 2011;40:1213–20.
  • Yoshiji H, Noguchi R, Ikenaka Y, Kaji K, Aihara Y, Yamazaki M, et al. Combination of branched-chain amino acids and angiotensin-converting enzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: a randomized control trial. Oncol Rep 2011;26:1547–53.
  • Ichikawa K, Okabayashi T, Maeda H, Namikawa T, Iiyama T, Sugimoto T, et al. Oral supplementation of branched-chain amino acids reduces early recurrence after hepatic resection in patients with hepatocellular carcinoma: a prospective study. Surg Today 2013;43:720–6.
  • Meng JY, Zhong JH, Zhang HG, Zhong W, Huang Z, Jin Y, et al. Pre-, peri-, and postoperative oral administration of branched-chain amino acids for primary liver cancer patients for hepatic resection: a systematic review. Nutr Cancer 2013; Epub ahead of print.
  • Chen K, Xia Y, Wang H, Xiao F, Xiang G, Shen F. Adjuvant iodine-125 brachytherapy for hepatocellular carcinoma after complete hepatectomy: a randomized controlled trial. PLoS One 2013;8:e57397.
  • Miao HQ, Liu H, Navarro E, Kussie P, Zhu Z. Development of heparanase inhibitors for anti-cancer therapy. Curr Med Chem 2006;13:2101–11.
  • Liu CJ, Lee PH, Lin DY, Wu CC, Jeng LB, Lin PW, et al. Heparanase inhibitor PI-88 as adjuvant therapy for hepatocellular carcinoma after curative resection: a randomized phase II trial for safety and optimal dosage. J Hepatol 2009;50:958–68.
  • Doffoel M, Bonnetain F, Bouche O, Vetter D, Abergel A, Fratté S, et al. Fédération Francophone de Cancérologie Digestive. Multicentre randomised phase III trial comparing Tamoxifen alone or with Transarterial Lipiodol Chemoembolisation for unresectable hepatocellular carcinoma in cirrhotic patients (Federation Francophone de Cancerologie Digestive 9402). Eur J Cancer 2008;44:528–38.
  • Verset G, Verslype C, Reynaert H, Borbath I, Langlet P, Vandebroek A, et al. Efficacy of the combination of long-acting release octreotide and tamoxifen in patients with advanced hepatocellular carcinoma: a randomised multicentre phase III study. Br J Cancer 2007;97:582–8.
  • Barbare JC, Bouche O, Bonnetain F, Raoul JL, Rougier P, Abergel A, et al. Randomized controlled trial of tamoxifen in advanced hepatocellular carcinoma. J Clin Oncol 2005;23:4338–46.
  • Nowak AK, Stockler MR, Chow PK, Findlay M. Use of tamoxifen in advanced-stage hepatocellular carcinoma. A systematic review. Cancer 2005;103:1408–14.
  • Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378–90.
  • Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, 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.
  • Hsu CH, Kang YK, Yang TS, Shun CT, Shao YY, Su WC, et al. Bevacizumab with erlotinib as first-line therapy in Asian patients with advanced hepatocellular carcinoma: a multicenter phase II study. Oncology 2013;85:44–52.
  • Zhu AX, Ancukiewicz M, Supko JG, Sahani DV, Blaszkowsky LS, Meyerhardt JA, et al. Efficacy, safety, pharmacokinetics, and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: a phase II study. Clin Cancer Res 2013;19:1557–66.
  • Santoro A, Rimassa L, Borbath I, Daniele B, Salvagni S, Van Laethem JL, et al. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol 2013;14:55–63.
  • Boige V, Malka D, Bourredjem A, Dromain C, Baey C, Jacques N, et al. Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma. Oncologist 2012;17:1063–72.
  • Hsu C, Yang TS, Huo TI, Hsieh RK, Yu CW, Hwang WS, et al. Vandetanib in patients with inoperable hepatocellular carcinoma: a phase II, randomized, double-blind, placebo-controlled study. J Hepatol 2012;56:1097–103.
  • Zhong JH, You XM, Gong WF, Ma L, Zhang Y, Mo QG, et al. Epidermal growth factor gene polymorphism and risk of hepatocellular carcinoma: a meta-analysis. PLoS One 2012;7:e32159.
  • Zhong JH, Xiang BD, Ma L, You XM, Li LQ, Xie GS. Meta-analysis of microsomal epoxide hydrolase gene polymorphism and risk of hepatocellular carcinoma. PLoS One 2013;8:e57064.
  • El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology 2008;134:1752–63.
  • Shi M, Guo RP, Lin XJ, Zhang YQ, Chen MS, Zhang CQ, et al. Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma: a prospective randomized trial. Ann Surg 2007;245:36–43.
  • Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer 2000;89:500–7.
  • Portolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, et al. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg 2006;243:229–35.
  • Sun HC, Zhang W, Qin LX, Zhang BH, Ye QH, Wang L, et al. Positive serum hepatitis B e antigen is associated with higher risk of early recurrence and poorer survival in patients after curative resection of hepatitis B-related hepatocellular carcinoma. J Hepatol 2007;47:684–90.
  • Yamanaka N, Takada M, Tanaka T, Yamanaka J, Yasui C, Ando T, et al. Viral serostatus and coexisting inflammatory activity affect metachronous carcinogenesis after hepatectomy for hepatocellular carcinoma. A further report. J Gastroenterol 2000;35:206–13.
  • Kaibori M, Ishizaki M, Matsui K, Kwon AH. Predictors of microvascular invasion before hepatectomy for hepatocellular carcinoma. J Surg Oncol 2010;102:462–8.
  • Funaki NO, Tanaka J, Seto SI, Kasamatsu T, Kaido T, Imamura M. Hematogenous spreading of hepatocellular carcinoma cells: possible participation in recurrence in the liver. Hepatology 1997;25:564–8.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.