Postoperative therapy options for hepatocellular carcinoma

Scandinavian Journal of Gastroenterology

Volumn 49, Issue 6, 2014, Pages 649-661

  Zhong, Jian Hong ^a   Ma, Liang ^a   Li, Le Qun ^a  

^a GUANGXI MEDICAL UNIVERSITY   (China)

Author keywords

Adjuvant; Chemoprevention; Hepatic resection; Hepatocellular carcinoma; Recurrence

Indexed keywords

ADEFOVIR DIPIVOXIL; ALPHA INTERFERON; BETA INTERFERON; BRANCHED CHAIN AMINO ACID; CAPECITABINE; CARBOPLATIN; CARMOFUR; CISPLATIN; DOXORUBICIN; EPIRUBICIN; FARNOQUINONE; FLUOROURACIL; GELATIN SPONGE; INTERFERON; IODINATED POPPYSEED OIL; IODINATED POPPYSEED OIL I 131; IODINE 125; IODINE 131; LAMIVUDINE; MITOMYCIN; MUPARFOSTAT; NUCLEOSIDE DERIVATIVE; OCTREOTIDE; RETINOID; SORAFENIB; TAMOXIFEN; TEGAFUR; TUMOR VACCINE; UFT; UNCLASSIFIED DRUG; VIRUS DNA; ANTINEOPLASTIC AGENT; ANTIVIRUS AGENT;

ADOPTIVE IMMUNOTHERAPY; ANTIVIRAL THERAPY; BRACHYTHERAPY; CANCER ADJUVANT THERAPY; CANCER CHEMOTHERAPY; CANCER IMMUNIZATION; CANCER MORTALITY; CANCER RECURRENCE; CHEMOEMBOLIZATION; CHILL; COHORT ANALYSIS; DRUG EFFICACY; DRUG WITHDRAWAL; EVENT FREE SURVIVAL; FATIGUE; FEVER; HEADACHE; HEPATITIS; HEPATITIS B VIRUS; HEPATITIS C VIRUS; HIGH RISK PATIENT; HUMAN; LEUKOPENIA; LIVER CELL CARCINOMA; LONG TERM SURVIVAL; MULTIPLE CYCLE TREATMENT; MYALGIA; OVERALL SURVIVAL; POSTOPERATIVE CARE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECURRENCE FREE SURVIVAL; REVIEW; SHORT TERM SURVIVAL; SINGLE DRUG DOSE; THROMBOCYTOPENIA; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT; VIRUS LOAD; ADJUVANT CHEMOTHERAPY; ADJUVANT THERAPY; CARCINOMA, HEPATOCELLULAR; DISEASE FREE SURVIVAL; HEPATITIS B; HEPATITIS C; LIVER NEOPLASMS; NEOPLASM RECURRENCE, LOCAL; SURVIVAL RATE; VIROLOGY;

ANTINEOPLASTIC AGENTS; ANTIVIRAL AGENTS; CARCINOMA, HEPATOCELLULAR; CHEMOEMBOLIZATION, THERAPEUTIC; CHEMOTHERAPY, ADJUVANT; DISEASE-FREE SURVIVAL; HEPATITIS B; HEPATITIS C; HUMANS; INTERFERON-ALPHA; LAMIVUDINE; LIVER NEOPLASMS; NEOPLASM RECURRENCE, LOCAL; POSTOPERATIVE CARE; RADIOTHERAPY, ADJUVANT; SURVIVAL RATE;

EID: 84901483158     PISSN: 00365521     EISSN: 15027708     Source Type: Journal    
DOI: 10.3109/00365521.2014.905626     Document Type: Review

References (119)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30
2. 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. (Pubitemid 32141852
3. 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
4. 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
5. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907-17. (Pubitemid 37518510
6. 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
7. de Lope CR, Tremosini S, Forner A, Reig M, Bruix J. Management of HCC. J Hepatol 2012;56:S75-87
8. 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
9. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet 2012;379:1245-55
10. 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
11. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005;42:1208-36. (Pubitemid 43112690
12. 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
13. 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
14. 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 hepatitisC virus-related liver cancer. Hepatology 2000;32:228-32. (Pubitemid 30614654
15. 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. (Pubitemid 34595504
16. 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
17. 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. (Pubitemid 46809282
18. 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. (Pubitemid 36205926
19. 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
20. 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. (Pubitemid 44970357
21. Breitenstein S, Dimitroulis D, Petrowsky H, Puhan MA, Mullhaupt B, Clavien PA. Systematic review and metaanalysis of interferon after curative treatment of hepatocellular carcinoma in patients with viral hepatitis. Br J Surg 2009;96:975-81
22. 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
23. 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
24. 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
25. 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
26. 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
27. 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
28. 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 metaanalysis of randomized controlled trials. Int J Cancer 2009; 124:2982-8
29. 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
30. Wang J, He XD, Yao N, Liang WJ, Zhang YC. A metaanalysis of adjuvant therapy after potentially curative treatment for hepatocellular carcinoma. Can J Gastroenterol 2013;27:351-63
31. 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
32. 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
33. Yamazhan T, Kurtaran B, Pullukçu H, Yüksel E, Ozkaya D, Taşbakan MI, et al. Pegylated interferon in HBeAg-positive and-negativechronichepatitisBpatients:post-Treatment1-year results of three Turkish centres. J Chemother 2013; In press
34. 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. (Pubitemid 37491552
35. 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
36. 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. (Pubitemid 43076891
37. 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
38. 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
39. 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
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
41. 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
42. 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. (Pubitemid 46434993
43. 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. (Pubitemid 43238454
44. Yoshiji H, Noguchi R, Toyohara M, Ikenaka Y, Kitade M, Kaji K, et al. Combination of vitamin K2 and angiotensinconverting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma. JHepatol 2009;51:315-21
45. 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
46. 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
47. 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
48. Zhong JH, Gong WF, Li LQ, You XM, Ma L, Xiang BD, Peng NF. Meta-Analysis of postoperative chemopreventive VitaminK2analog for patients with hepatocellular carcinoma. J Gastroenterol Hepatol 2012;27:212-13
49. 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. (Pubitemid 26177483
50. 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-Termfollow-up data. Intervirology 2005;48:39-45. (Pubitemid 40529209
51. 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. (Pubitemid 29157643
52. Zhong JH, Li LQ. Postoperative adjuvant transarterial chemoembolization for participants with hepatocellular carcinoma: A meta-Analysis. Hepatol Res 2010;40:943-53
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. (Pubitemid 24233352
54. 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
55. 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. (Pubitemid 44651423
56. 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
57. 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
58. 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. JGastroenterolHepatol 2003;18:450-5. (Pubitemid 36549557
59. 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. (Pubitemid 35174678
60. 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. (Pubitemid 36693726
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
62. 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
63. 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
64. 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. (Pubitemid 28092919
65. 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. (Pubitemid 27007323
66. 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
67. 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. (Pubitemid 32552825
68. 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. (Pubitemid 29110405
69. 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
70. 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
71. 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. (Pubitemid 26083165
72. 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. (Pubitemid 46489553
73. 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
74. Zhong JH, Li LQ. Conventional oral systemic chemotherapy for postoperative hepatocellular carcinoma. J Canc Res Updates 2014;3:11-18
75. 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
76. 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
77. 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 shortterm recurrence rates of hepatocellular carcinomas. J Immunother 2008;31:63-71. (Pubitemid 351619405
78. 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
79. 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
80. 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. (Pubitemid 38435545
81. 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
82. 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
83. 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
84. 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. (Pubitemid 30127660
85. 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
86. 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
87. 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
88. Ke Y, Ma L, You XM, Huang SX, Liang YR, Xiang BD, et al. Antiviral therapy for hepatitis B virusrelated hepatocellular carcinoma after radical hepatectomy. Cancer Biol Med 2013;10:158-64
89. Zhong JH, Li LQ, Wu LC. Lamivudine with or without adefovir dipivoxil for postoperative hepatocellular carcinoma. Cochrane Database Syst Rev 2011:CD008713
90. 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
91. 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. (Pubitemid 29519301
92. 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
93. 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
94. 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
95. 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
96. 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
97. 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. (Pubitemid 44132602
98. 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
99. 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
100. Verset G, Verslype C, Reynaert H, Borbath I, Langlet P, Vandebroek A, et al. Efficacy of the combination of longacting release octreotide and tamoxifen in patients with advanced hepatocellular carcinoma: A randomised multicentre phase III study. Br J Cancer 2007;97:582-8. (Pubitemid 47339881
101. 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. (Pubitemid 46207007
102. Nowak AK, Stockler MR, Chow PK, Findlay M. Use of tamoxifen in advanced-stage hepatocellular carcinoma. A systematic review. Cancer 2005;103:1408-14. (Pubitemid 40410736
103. 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 JMed 2008;359:378-90
104. 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
105. HsuCH,KangYK,YangTS, ShunCT,ShaoYY,SuWC,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
106. 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
107. 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
108. 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
109. 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, doubleblind, placebo-controlled study. J Hepatol 2012;56: 1097-103
110. 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
111. 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
112. El-Serag HB, Marrero JA, Rudolph L, Reddy KR. Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology 2008;134:1752-63. (Pubitemid 351615415
113. 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. (Pubitemid 46035433
114. 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. (Pubitemid 30640096
115. 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. (Pubitemid 43185442
116. 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. (Pubitemid 47503431
117. 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. (Pubitemid 30195633
118. Kaibori M, Ishizaki M, Matsui K, Kwon AH. Predictors of microvascular invasion before hepatectomy for hepatocellular carcinoma. J Surg Oncol 2010;102:462-8
119. 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. (Pubitemid 27106434