Management of Hepatocellular Carcinoma

Surgical Clinics of North America

Volumn 93, Issue 6, 2013, Pages 1423-1450

  Asham, Emad H ^a   Kaseb, Ahmed ^b   Ghobrial, R Mark ^a  

^a HOUSTON METHODIST HOSPITAL   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Hepatocellular carcinoma (HCC); Liver resection; Liver transplant; Locoregional therapy; Systemic therapy

Indexed keywords

AFLATOXIN; ALCOHOL; ALEMTUZUMAB; ALPHA2B INTERFERON; BASILIXIMAB; BEVACIZUMAB; BILIRUBIN; CALCINEURIN INHIBITOR; CETUXIMAB; CISPLATIN; CYCLOSPORIN; DACLIZUMAB; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; FLUOROURACIL; HEPATITIS VACCINE; LAPATINIB; MITOMYCIN; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; NOLATREXED; PROTEIN P53; RAPAMYCIN; SERUM ALBUMIN; SMALL INTERFERING RNA; SORAFENIB; TACROLIMUS; TIVANTINIB; YTTRIUM 90;

ABDOMINAL PAIN; ABLATION THERAPY; ALCOHOLIC FATTY LIVER; BILE DUCT CARCINOMA; BILIARY TRACT DISEASE; BILIRUBIN BLOOD LEVEL; BLOOD TRANSFUSION; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER GENE THERAPY; CANCER PROGNOSIS; CANCER SCREENING; CANCER STAGING; CANCER SURVIVAL; CHEMOEMBOLIZATION; CHILD PUGH SCORE; CHOLECYSTITIS; CHRONIC LIVER DISEASE; CIRCULATING TUMOR CELL; COLORECTAL LIVER METASTASIS; COMPUTER ASSISTED TOMOGRAPHY; CRYOTHERAPY; DIABETES MELLITUS; DIARRHEA; DISEASE FREE SURVIVAL; DISEASE SURVEILLANCE; ECHOGRAPHY; ELASTOGRAPHY; ELECTROPORATION; EXTERNAL BEAM RADIOTHERAPY; FATIGUE; HEMOSIDEROSIS; HEPATITIS A; HEPATITIS B; HEPATITIS C; HEPATITIS E; HUMAN; HYPERTENSION; IMMUNOHISTOCHEMISTRY; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; LAPAROTOMY; LIVER ADENOMA; LIVER CANCER; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FAILURE; LIVER HYPERTROPHY; LIVER RESECTION; LIVER TOXICITY; LIVER TRANSPLANTATION; LOW LEVEL LASER THERAPY; META ANALYSIS (TOPIC); MICROWAVE THERAPY; MOLECULARLY TARGETED THERAPY; NAUSEA; NEODYMIUM YAG LASER; NONALCOHOLIC FATTY LIVER; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OBESITY; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); POSITRON EMISSION TOMOGRAPHY; POSTOPERATIVE COMPLICATION; PRIORITY JOURNAL; PROTHROMBIN TIME; PROTON THERAPY; RADIATION DOSE; RADIATION INJURY; RADIOFREQUENCY; RADIOFREQUENCY ABLATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RASH; RECURRENCE FREE SURVIVAL; REVIEW; SCHISTOSOMIASIS; SKIN EXFOLIATION; STOMACH CANCER; THROMBOCYTE COUNT; TREATMENT RESPONSE; TUMOR ABLATION; TUMOR VASCULARIZATION; VEIN OCCLUSION; VIRUS REPLICATION; VOMITING;

HEPATOCELLULAR CARCINOMA (HCC); LIVER RESECTION; LIVER TRANSPLANT; LOCOREGIONAL THERAPY; SYSTEMIC THERAPY;

CARCINOMA, HEPATOCELLULAR; CATHETER ABLATION; CHEMOEMBOLIZATION, THERAPEUTIC; COMORBIDITY; DISEASE PROGRESSION; ELECTROPORATION; END STAGE LIVER DISEASE; FATTY LIVER; GENETIC THERAPY; HEPATITIS VIRUSES; HEPATITIS, VIRAL, HUMAN; HUMANS; LIVER CIRRHOSIS; LIVER NEOPLASMS; LIVER TRANSPLANTATION; NEOPLASM RECURRENCE, LOCAL; RISK FACTORS; SEVERITY OF ILLNESS INDEX; VIRUS REPLICATION;

EID: 84887214538     PISSN: 00396109     EISSN: 15583171     Source Type: Journal    
DOI: 10.1016/j.suc.2013.08.008     Document Type: Review

References (170)

1. Centre for Disease Control and Prevention (CDC) Hepatocellular carcinoma in the United States, 2001-2006. MMWR Morb Mortal Wkly Rep 2010, 59(17):517-520.
2. El-Serag H.B., Rudolph K.L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007, 132:2557-2576.
3. Carreno V., Bartolome J., Castillo I., et al. Occult hepatitis B virus and hepatitis Cvirus infections. Rev Med Virol 2008, 18:139-157.
4. Abdel-Aziz F., Habib M., Mohamed M.K., et al. Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence. Hepatology 2000, 32:111-115.
5. Kim C.M., Koike K., Saito I., et al. HBX gene of hepatitis B virus induced liver cancer in transgenic mice. Nature 1991, 351:317-320.
6. Truant R., Antunovic J., Greenblatt J., et al. Direct interaction of hepatitis B virus HBX protein with p53 leads to inhibition by HBx of p 53 response element-directed transactivation. JVirol 1995, 69:1851-1859.
7. Chang M., Chen C., Mei-Shu Lai M., et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. NEngl J Med 1997, 336:1855-1859.
8. Cammà C., Giunta M., Andreone P., et al. Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach. JHepatol 2001, 34(4):593-602.
9. International Agency for Research on Cancer Hepatitis viruses. IARC monographs on the evaluation of carcinogenic risks to humans 1994, vol. 59. IARC, Lyon (France).
10. Verme G., Brunetto M.R., Oliveri F., et al. Role of hepatitis delta virus infection in hepatocellular carcinoma. Dig Dis Sci 1991, 36:1134-1136.
11. Degos F., Christidis C., Ganne-Carrie N., et al. Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death. Gut 2000, 47:131-136.
12. Kew M.C. Hepatitis B and C viruses and hepatocellular carcinoma. Clin Lab Med 1996, 16:395-406.
13. Friedman S. Mechanisms of disease: mechanisms of hepatic fibrosis and therapeutic implications. Nat Clin Pract Gastroenterol Hepatol 2004, 1:98-105.
14. Koshy R., Maupas P., Muller R., et al. Detection of hepatitis B virus-specific DNA in the genomes of human hepatocellular carcinoma and liver cirrhosis tissues. JGen Virol 1981, 57(Pt 1):95-102.
15. Xu Z., Jensen G., Yen T.S. Activation of hepatitis B virus S promoter by the viral large surface protein via induction of stress in the endoplasmic reticulum. JVirol 1997, 71:7387-7392.
16. Donato F., Tagger A., Gelatti U., et al. Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol 2002, 155:323-331.
17. Morgan T.R., Mandayam S., Jamal M.M. Alcohol and hepatocellular carcinoma. Gastroenterology 2004, 127(5 Suppl 1):S87-S96.
18. Callee E.E., Rodriguez C., Walker-Thurmond K., et al. Overweight, obesity and mortality from cancer in a prospective studied cohort of US adults. NEngl J Med 2003, 348:1625-1638.
19. Hassan M., Hwang L., Hatten C.J., et al. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology 2002, 36(5):1206-1213.
20. Shimada M., Hashimoto E., Taniai M., et al. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. JHepatol 2002, 37:154-160.
21. McCollough A.J. The clinical features, diagnosis and natural history of non-alcoholic fatty liver disease. Clin Liver Dis 2004, 8:521-533.
22. Finch S.C., Finch C.A. Idiopathic hemochromatosis and iron storage disease: A.Iron metabolism in hemochromatosis. Medicine 1995, 34:381-430.
23. Primary Biliary Cirrhosis. Sherlock's diseases of the liver and biliary system 2011, 338-342. Blackwell Science, Edinburgh (United Kingdom). 12th edition. M. Bassendine, S. Rushbrook, R. Chapman (Eds.).
24. Farinati F., Floreani A., De Maria N., et al. Hepatocellular carcinoma in primary biliary cirrhosis. JHepatol 1994, 21(3):315-316.
25. Hassan M.M., Zaghloul A.S., El-Serag H.B., et al. The role of hepatitis C in hepatocellular carcinoma: a case control study among Egyptian patients. JClin Gastroenterol 2001, 33:123-126.
26. Takayasu K., Muramatsu Y., Moriyama N., et al. Radiological study of idiopathic Budd-Chiari syndrome complicated by hepatocellular carcinoma. A report of four cases. Am J Gastroenterol 1994, 89(2):249-253.
27. Havlioglu N., Brunt E.M., Bacon B.R. Budd-Chiari syndrome and hepatocellular carcinoma: a case report and review of the literature. Am J Gastroenterol 2003, 98:201-204.
28. Belghiti J., Vilgrain V., Paradis V. Benign liver lesions. Surgery of the liver and biliary tract and the pancreas 2007, 1142-1143. Saunders, Edniburgh (United Kingdom). 4th edition. L.H. Blumgart (Ed.).
29. Bioulac-Sage P., Laumonier H., Couchy G., et al. Hepatology 2009, 50(2):481-489.
30. Bioulac-Sage P., Rebouissou S., Thomas C., et al. Hepatology 2007, 46(3):740-748.
31. Liu Y., Chang C.C., Marsh G.M., et al. Population attributable risk of aflatoxin-related liver cancer: systematic review and meta-analysis. Eur J Cancer 2012, 48(14):2125-2136.
32. Kuper H., Tzonou A., Kaklamani E., et al. Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma. Int J Cancer 2000, 85(4):498-502.
33. Trevisani F., Cantarini M.C., Labate A.M., et al. Surveillance for hepatocellular carcinoma in elderly Italian patients with cirrhosis: effects on cancer staging and patient survival. Am J Gastroenterol 2004, 99:1470-1476.
34. Wong V., Chan S., Mo F., et al. Clinical scoring system to predict hepatocellular carcinoma in chronic hepatitis B carriers. JClin Oncol 2010, 28(10):1660-1665.
35. Imbert-Bismut F., Ratziu V., Pieroni L., et al. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet 2001, 357:1069-1075.
36. Moriyama M., Matsumura H., Aoki H., et al. Long-term outcome, with monitoring of platelet counts, in patients with chronic hepatitis C and liver cirrhosis after interferon therapy. Intervirology 2003, 46:296-307.
37. Befrits R., Hedman M., Blomquist L., et al. Chronic hepatitis C in alcoholic patients: prevalence, genotypes, and correlation to liver disease. Scand J Gastroenterol 1995, 30:1113-1118.
38. Ong J.P., Pitts A., Younossi Z.M. Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. JHepatol 2008, 49:608-612.
39. Silveira M.G., Suzuki A., Lindor K.D. Surveillance for hepatocellular carcinoma in patients with primary biliary cirrhosis. Hepatology 2008, 48(4):1149-1156.
40. Fracanzani A.L., Conte D., Fraquelli M., et al. Increased cancer risk in a cohort of 230 patients with hereditary hemochromatosis in comparison to matched control patients with non-iron related chronic liver disease. Hepatology 2001, 33:647-651.
41. Izzo F., Cremona F., Ruffolo F., et al. Outcome of 67 patients with hepatocellular cancer detected during screening of 1125 patients with chronic hepatitis. Ann Surg 1998, 227:513-518.
42. Sherman M. Surveillance for hepatocellular carcinoma and early diagnosis. Clin Liver Dis 2007, 11:817-837.
43. Peterson M., Baron R., Marsh W., et al. Pretransplantation surveillance for possible hepatocellular carcinoma in patients with cirrhosis: epidemiology and CT-based tumor detection rate in 430 cases with surgical pathologic correlation. Radiology 2000, 217:743-749.
44. Bolondi L., Sofia S., Siringo S., Gaiani S., et al. Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost-effectiveness analysis. Gut 2001, 48:251-259.
45. Masuzaki R., Tateishi R., Yoshida H., et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology 2009, 49(6):296-307.
46. Burix J., Sherman M. Management of hepatocellular carcinoma. AASLD practice guidelines. Hepatology 2005, 42(5):1208-1236.
47. Burix J., Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011, 53(3):1020-1022.
48. Sato Y., Sekine T., Ohwada S. Alpha-fetoprotein-producing rectal cancer: calculated tumor marker doubling time. JSurg Oncol 1994, 55:265-268.
49. Adachi Y., Tsuchihashi J., Shiraishi N., et al. AFP-producing gastric carcinoma: multivariate analysis of prognostic factors in 270 patients. Oncology 2003, 65:95-101.
50. Li D., Mallorya T., Satomurab S. AFP-L3: a new generation of tumor marker for hepatocellular carcinoma. Clin Chim Acta 2001, 313(1-2):15-19.
51. Paradis V., Degos F., Dargere D., et al. Identification of a new marker of hepatocellular carcinoma by serum protein profiling of patients with chronic liver diseases. Hepatology 2005, 41:40-47.
52. Lok A., Sterling R., Everhart J., et al. HALT-C Trial Group. Des-γ-carboxy prothrombin and α-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology 2010, 138(2):493-502.
53. Zinkin N., Grall F., Bhaskar K., et al. Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. Clin Cancer Res 2008, 15(14):470.
54. Bennett G.L., Krinsky G., Abitbol R., et al. Sonographic detection of hepatocellular carcinoma and dysplastic nodules in cirrhosis. Correlation of pretransplantation sonography and liver explant pathology in 200 patients. AJR Am J Roentgenol 2002, 179:75-80.
55. Wilson S.R., Burns P.N., Muradali D., et al. Harmonic hepatic US with microbubble contrast agent: initial experience showing improved characterization of hemangioma, hepatocellular carcinoma, and metastasis. Radiology 2000, 215:153-161.
56. Kim T., Murakami T., Takahashi S., et al. Optimal phases of dynamic CT for detecting hepatocellular carcinoma: evaluation of unenhanced and triple-phase images. Abdom Imaging 1999, 24:473-480.
57. Ito K. Hepatocellular carcinoma: conventional MRI findings including gadolinium-enhanced dynamic imaging. Eur J Radiol 2006, 58(2):186-199.
58. Yamshita Y., Mitsuzaki K., Yi T., et al. Small hepatocellular carcinoma in patient with chronic liver damage: prospective comparison of detection with dynamic MR imaging and helical CT of the whole liver. Radiology 1996, 200:79-84.
59. Shimizu A., Ito K., Koike S., et al. Cirrhosis or chronic hepatitis: evaluation of small (or 2-cm) early-enhancing hepatic lesions with serial contrast-enhanced dynamic MR imaging. Radiology 2003, 226:550-555.
60. Kashiwagi T. PDG-PET and hepatocellular carcinoma. JGastroenterol 2004, 39:1017-1018.
61. Stigliano R., Marelli L., Yu D., et al. 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(5):437-447.
62. Child C.G., Turcotte J.G. Surgery and portal hypertension. The liver and portal hypertension 1964, 50-64. Saunders, Philadelphia. C.G. Child (Ed.).
63. Pugh R.N., Murray-Lyon I.M., Dawson J.L., et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973, 60:648-652.
64. Okuda K., Ohtsuki T., Obata H., et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 1985, 56:918-928.
65. Malinchoc M., Kamath P., Gordon F., et al. Amodel to predict poor survival in patients undergoing transjugular portosystemic shunts. Hepatology 2000, 31:864-871.
66. Llovet J.M., Bru C., Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999, 19:329-338.
67. Wildi S., Petalozzi B., McCormack L., et al. Critical evaluation of the different staging systems for hepatocellular carcinoma. Br J Surg 2004, 91:400-408.
68. Llovet J.M., Burroughs A., Bruix J. Hepatocellular carcinoma. Lancet 2003, 362(9399):1907-1917.
69. Llovet J.M. Updated treatment approach to hepatocellular carcinoma. JGastroenterol 2005, 40:225-235.
70. Llovet J.X., Bruix J., Gores G.J. Surgical resection versus transplantation for early hepatocellular carcinoma. Clues for the best therapy. Hepatology 2000, 31:1019-1021.
71. Yamanaka J., Saito S., Fujimoto J. Impact of preoperative planning using virtual segmental volumetry on liver resection for hepatocellular carcinoma. World J Surg 2007, 31:1249-1255.
72. Vauthey J.N., Chaoui A., Do K.A. Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical association. Surgery 2000, 127:512-519.
73. Hashimoto M., Watanabe G. Hepatic parenchymal cell volume and the indocyanine green tolerance test. JSurg Res 2000, 92:222-227.
74. Fong Y., Sun R.L., Jarnagin W., et al. An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg 1999, 229:790-799.
75. Imamura H., Matsuyama Y., Tanaka E., et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. JHepatol 2003, 38:200-207.
76. Maithel S.K., Kneuertz P.J., Kooby D.A., et al. Importance of low preoperative platelet count in selecting patients for resection of hepatocellular carcinoma: a multi-institutional analysis. JAm Coll Surg 2011, 212(4):638-648. [discussion: 648-50].
77. Makuuchi M., Thai B.L., Takayasu K., et al. Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery 1990, 107:521-527.
78. Kokudo N., Makuuchi M. Current role of portal vein embolization/hepatic artery chemoembolization. Surg Clin North Am 2004, 84:643-657.
79. Abdalla E.K., Hicks M.E., Vauthey J.N. Portal vein embolization: rationale, technique and future prospects. Br J Surg 2001, 88:165-175.
80. Ribero D., Abdalla E., Madoff D., et al. Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome. Br J Surg 2007, 94:1386-1394.
81. Nagino M., Nimura Y., Kamiya J., et al. Immediate increase in arterial blood flow in embolized hepatic segments after portal vein embolization: CT demonstration. Am J Roentgenol 1998, 171:1037-1039.
82. Aoki K., Imamura H., Hasegawa K., et al. Sequential Preoperative arterial and portal venous embolizations in patients with hepatocellular carcinoma. Arch Surg 2004, 139:766-774.
83. Abulkhir A., Limongelli P., Healey A.J., et al. Preoperative portal vein embolization for major liver resection: a meta-analysis. Ann Surg 2008, 247(1):49-57.
84. Pai M., Zacharoulis D., Milicevic M.N., et al. Autologous infusion of expanded mobilized adult bone marrow-derived CD34+ cells into patients with alcoholic liver cirrhosis. Am J Gastroenterol 2008, 103(8):1952-1958.
85. am Esch J.S., Knoefel W.T., Klein M., et al. Portal application of autologous CD133+ bone marrow cells to the liver: a novel concept to support hepatic regeneration. Stem Cells 2005, 23(4):463-470.
86. Stremitzer S., Tamandl D., Kaczirek K., et al. Value of hepatic venous pressure gradient measurement before liver resection for hepatocellular carcinoma. Br J Surg 2011, 98(12):1752-1758.
87. Boleslawski E., Petrovai G., Truant S., et al. Hepatic venous pressure gradient in the assessment of portal hypertension before liver resection in patients with cirrhosis. Br J Surg 2012, 99(6):855-863.
88. Cherqui D., Laurent A., Tayar C., et al. Laparoscopic liver resection for peripheral hepatocellular carcinoma in patients with chronic liver disease midterm results and perspectives. Ann Surg 2006, 243(4):499-502.
89. Jiao L.R., Ayav A., Navarra G., et al. Laparoscopic liver resection assisted by the laparoscopic Habib Sealer. Surgery 2008, 144(5):770-774.
90. Azoulay D., Andreani P., Maggi U. Combined liver resection and reconstruction of the supra- renal vena cava: the Paul Brousse experience. Ann Surg 2006, 244:80-88.
91. Lang H., Radtke A., Hindennach M., et al. Impact of virtual tumor resection and computer-assisted risk analysis on operation planning and intraoperative strategy in major hepatic resection. Arch Surg 2005, 140:629-638.
92. Clinical Trials. Evaluation of image-guided liver surgical system for resection of liver cancer. US National Institute of Health. Available at:. http://clinicaltrials.gov/ct2/show/NCT00782886.
93. Mazzaferro V., Regalia E., Doci R., et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. NEngl J Med 1996, 334:693-699.
94. Breitenstein S., Dimitroulis D., Petrowsky H., et al. Systematic review and meta-analysis of interferon after curative treatment of hepatocellular carcinoma in patients with viral hepatitis. Br J Surg 2009, 96:975-981.
95. Iwatzuki S., Gordon R., Sahw B., et al. Role of liver transplantation in cancer therapy. Ann Surg 1985, 202(40):401-407.
96. Yao F.Y., Ferrell L., Bass N.M., et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 2001, 33:1394-1403.
97. Adler M., De Pauw F., Vereerstraeten P., et al. Outcome of patients with hepatocellular carcinoma listed for liver transplantation within the Eurotransplant allocation system. Liver Transpl 2008, 14:526-533.
98. DuBay D., Sandroussi C., Sandhu L., et al. Liver transplantation for advanced hepatocellular carcinoma using poor tumor differentiation on biopsy as an exclusion criterion. Ann Surg 2011, 253:166-172.
99. Rougier P., Mitrya E., Barbareb J.C., et al. Hepatocellular carcinoma (HCC): an update. Semin Oncol 2007, 34(Suppl 1):S12-S20.
100. Singhal A., Jayaraman M., Dhanasekaran D., et al. Molecular and serum markers in hepatocellular carcinoma: predictive tools for prognosis and recurrence. Crit Rev Oncol Hematol 2012, 82(2):116-140.
101. Mazzaferro V., Llovet J.M., 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.
102. Yao F.Y., Hirose R., LaBerge J.M. Aprospective study on downstaging hepatocellular carcinoma prior to liver transplantation. Liver Transpl 2005, 11:505-514.
103. Graziadei I., Sandmueller H., Waldenberger P., et al. Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome. Liver Transpl 2003, 9(6):557-563.
104. United Network of Organ Sharing. Available at:. http://www.unos.org.
105. Klintmalm G.B., Davis G.L., Teperman L., et al. Arandomized, multicenter study comparing steroid-free immunosuppression and standard immunosuppression for liver transplant recipients with chronic hepatitis C. Liver Transpl 2011, 17(12):1394-1403.
106. Toso C., Merani S., Bigam D., et al. Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma. Hepatology 2009, 51(4):1237-1243.
107. Decaens T., Roudot-Thoraval F., Bresson-Handi S., et al. Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: a multicenter study of 412 patients. World J Gastroenterol 2006, 12(45):7319-7325.
108. Vakili K., Pomposelli J.J., Cheah Y.L., et al. Living donor liver transplantation for hepatocellular carcinoma: increased recurrence but improved survival. Liver Transpl 2009, 15:1861-1866.
109. Montorsi M., Santambrogio R., Bianchi P., et al. Radiofrequency interstitial thermal ablation of hepatocellular carcinoma in liver cirrhosis. Role of the laparoscopic approach. Surg Endosc 2001, 15:141-145.
110. Curley S., Izzo F., Ellis L.M., et al. Radiofrequency ablation of hepatocellular carcinoma in 110 patients with cirrhosis. Ann Surg 2000, 232:381-391.
111. Siperstein A.E., Rogers S.J., Hansen P.D., et al. Laparoscopic thermal ablation of hepatic neuroendocrine tumor metastases. Surgery 1997, 122:1147-1155.
112. Wood T.F., Rose D.M., Chung M., et al. Radiofrequency ablation of 231 unresectable hepatic tumours: indications, limitations and complications. Ann Surg Oncol 2000, 7:593-600.
113. Solbiati L., Goldberg S.N., Ierace T., et al. Radio-frequency ablation of hepatic metastases: postprocedural assessment with a US microbubble contrast agent-early experience. Radiology 1999, 211:643-649.
114. Khorsandi S., Kysela P., Valek V., et al. Initial data on a novel endovascular radiofrequency catheter when used for arterial occlusion in liver cancer. Eur Surg 2009, 41(3):104-108.
115. Shina S., Tagawa K., Unuma T., et al. Percutaneous ethanol injection therapy for hepatocellular carcinoma. A histopathologic study. Cancer 1991, 68:1524-1530.
116. Livraghi T., Golberg S.N., Lazzaroni S., et al. Small hepatocellular carcinoma: treatment with radiofrequency ablation versus percutaneous ethanol injection. Radiology 1999, 210:655-661.
117. Hyodoh H., Hyodoh K., Takahashi K., et al. Microwave coagulation therapy on hepatomas: CT and MR appearance after therapy. JMagn Reson Imaging 1998, 2:451-458.
118. Seki S., Sakaguchi H., Kadoya H., et al. Laparoscopic microwave coagulation therapy for hepatocellular carcinoma. Endoscopy 2000, 32:591-597.
119. Giorgio A., Tarantino L., de Stefano G., et al. Interstitial laser photocoagulation under ultrasound guidance of liver tumors: results in 104treated patients. Eur J Ultrasound 2000, 11:181-188.
120. Wren S.M., Coburn M.M., Tan M., et al. Is cryosurgical ablation appropriate for treating hepatocellular cancer?. Arch Surg 1997, 132:599-603.
121. Seifert J.K., Morris D.L. World survey on the complications of hepatic and prostate cryotherapy. World J Surg 1999, 23:109-114.
122. Majno P.E., Adam R., Bismuth H., et al. Influence of preoperative transarterial Lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg 1997, 226:688-703.
123. Matsui O., Kadoya M., Yoshikawa J., et al. Subsegmental transcatheter arterial embolization for small hepatocellular carcinomas: local therapeutic effect and 5-year survival rate. Cancer Chemother Pharmacol 1994, 33(Suppl):S84-S88.
124. Llovet J.M., Real M.I., Montaña X., et al. Arterial embolisation or chemo-embolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002, 359(9319):1734-1739. Barcelona Liver Cancer Group.
125. Oliveri R.S., Wetterslev J., Gluud C. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma. Cochrane Database Syst Rev 2011, (3). CD004787.
126. Ernst O., Sergent G., Mizrahi D., et al. Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization: comparison of planned periodic chemoembolization and chemoembolization based on tumor response. Am J Roentgenol 1999, 172:59-64.
127. Varela M., Real M.I., Burrel M., et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. JHepatol 2007, 46:474-481.
128. 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. JHepatol 2012, 56(6):1330-1335.
129. Poon R.T., Ngan H., Lo C.M., et al. Transarterial chemoembolization for inoperable hepatocellular carcinoma and postresection intrahepatic recurrence. JSurg Oncol 2000, 73:109-114.
130. Yoo H.S., Park C.H., Lee J.T., et al. Small hepatocellular carcinoma: high dose internal radiation therapy with superselective intra-arterial injection of I-131-labeled Lipiodol. Cancer Chemother Pharmacol 1994, 33(Suppl):S128-S133.
131. 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(3):868-878. European Network on Radioembolization with Yttrium-90 Resin Microspheres (ENRY).
132. Kennedy A., Coldwell D., Sangro B., et al. Radioembolization for the treatment of liver tumors general principles. Am J Clin Oncol 2012, 35(1):91-99.
133. Dawson L.A., Normolle D., Balter J.M., et al. Analysis of radiation-induced liver disease using the Lyman NTCP model. Int J Radiat Oncol Biol Phys 2002, 53(4):810-821.
134. Mornex F., Girard N., Beziat C., et al. Feasibility and efficacy of high-dose three-dimensional conformal radiotherapy in cirrhotic patients with small-size hepatocellular carcinoma noneligible for curative therapies -mature results of the French phase-II RTF-1 trial. Int J Radiat Oncol Biol Phys 2006, 66:1152-1158.
135. Kim J.H., Park J.W., Kim T.H., et al. 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(3):813-819.
136. Chung Y.L., Jian J.J., Cheng S.H., et al. Sublethal irradiation induces vascular endothelial growth factor and promotes growth of hepatoma cells: implications for radiotherapy of hepatocellular carcinoma. Clin Cancer Res 2006, 12(9):2706-2715.
137. Camphausen K.A., Lawrence R.C. Principles of radiation therapy. Cancer management: a multidisciplinary approach 2008, CMP Healthcare Media, Lawrence (KS), Available at:, Accessed October 18, 2013. http://www.cancernetwork.com/cancer-management/page/1/0?gid=All%26domain_id=All, 11th edition. R. Pazdur, L.D. Wagman, K.A. Camphausen (Eds.).
138. Tse R.V., Hawkins M., Lockwood G., et al. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. JClin Oncol 2008, 26(4):657-664.
139. Tokuuye K, Akine Y, Hashimoto T, etal. Proton beam therapy alone for hepatocellular carcinoma. Abstract 132. Presented at Gastrointestinal Cancers Symposium. Hollywood (FL), January 27-29, 2005. Meeting proceedings. 2005; p. 149.
140. Bush D.A., Hillebrand D.J., Slater J.M., et al. The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. Cancer 2011, 117(13):3035-3059.
141. Bartolozzi C., Lencioni R., Caramella D., et al. Treatment of large HCC: transcatheter arterial chemoembolization combined with percutaneous ethanol injection versus repeated transcatheter arterial chemoembolization. Radiology 1995, 197:812-818.
142. Rossi S., Garbagnati F., Lencioni R., et al. Percutaneous radiofrequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply. Radiology 2000, 217:119-126.
143. Yoon S., Lim Y., Won H.J., 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.
144. Gish R.G., Porta C., Lazar L., et al. Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin. JClin Oncol 2007, 25:3069-3075.
145. Leung T.W., Patt Y.Z., Lau W.Y., et al. Complete pathological remission is possible with systemic combination chemotherapy for inoperable hepatocellular carcinoma. Clin Cancer Res 1999, 5:1676-1681.
146. Yeo W., Mok T.S., Zee B., et al. Arandomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma. JNatl Cancer Inst 2005, 97:1532-1538.
147. Kaseb A.O., Shindoh J., Patt Y.Z., et al. Modified cisplatin/interferon α-2b/doxorubicin/5-fluorouracil (PIAF) chemotherapy in patients with no hepatitis or cirrhosis is associated with improved response rate, resectability, and survival of initially unresectable hepatocellular carcinoma. Cancer 2013, 119(18):3334-3342.
148. Wilhelm S.M., Carter C., Tang L., et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004, 64:7099-7109.
149. Llovet J.M., Ricci S., Mazzaferro V., et al. Sorafenib in advanced hepatocellular carcinoma. NEngl J Med 2008, 359:378-390.
150. Schwartz J.D., Schwartz M., Lehrer D., et al. Bevacizumab in unresectable hepatocellular carcinoma (HCC) for patients without metastasis and without invasion of the portal vein. JClin Oncol (Meeting Abstracts) 2006, 24(18S). [abstract 4144].
151. Thomas M.B., Morris J.S., Chadha R., et al. Phase II trial of the combination of bevacizumab and erlotinib in patients who have advanced hepatocellular carcinoma. J Clin Oncol 2009, 27(6):843-850.
152. Kaseb A.O., Garrett-Mayer E., Morris J.S., et al. Efficacy of bevacizumab plus erlotinib for advanced hepatocellular carcinoma and predictors of outcome: final results of a phase II trial. Oncology 2012, 82(2):67-74.
153. Siegel A.B., Cohen E.I., Ocean A., et al. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol 2008, 26(18):2992-2998.
154. Boige V., Malka D., Bourredjem A., et al. Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma. Oncologist 2012, 17(8):1063-1072.
155. Sun W., Haller D.G., Mykulowycz K., et al. Combination of capecitabine, oxaliplatin with bevacizumab in treatment of advanced hepatocellular carcinoma (HCC): a phase II study. JClin Oncol (Meeting Abstracts) 2007, 25(18S). [abstract 4574].
156. Vogelstein B., Kinzler K.W. Cancer genes and the pathways they control. Nat Med 2004, 10:789-799.
157. Mendel D.B., Laird A.D., Xin X., et al. Invivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003, 9:327-337.
158. Hoda D, Catherine C, Strosberg J, etal. Phase II study of sunitinib malate in adult patients with metastatic or surgically unresectable hepatocellular carcinoma. Gastrointestinal Cancers Symposium, Orlando, January 25-27, 2008 (abstract 267).
159. Santoro A., Rimassa L., Borbath I., et al. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol 2013, 14(1):55-63.
160. Morimitsu Y., Hsia C.C., Kojiro M., et al. Nodules of less differentiated tumor within or adjacent to hepatocellular carcinoma: relative expression of transforming growth factor- alpha and its receptor in the different areas of tumor. Hum Pathol 1995, 26:1126-1132.
161. Philip P.A., Mahoney M.R., Allmer C., et al. Phase II study of erlotinib (OSI-774) in patients with advanced hepatocellular cancer. JClin Oncol 2005, 23:6657-6663.
162. Ramanathan R.K., Belani C.P., Singh D.A., et al. Aphase II study of lapatinib in patients with advanced biliary tree and hepatocellular cancer. Cancer Chemother Pharmacol 2009, 64:777-783.
163. Zhu A.X., Stuart K., Blaszkowsky L.S., et al. Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma. Cancer 2007, 110:581-589.
164. Gruenwald V., Wilkens L., Gebel M., et al. Aphase II open label study of cetuximab in unresectable hepatocellular carcinoma: final results. JClin Oncol (Meeting Abstracts) 2007, 25(18S). [abstract 4598].
165. Guo Y., Zhang Y., Klein R., et al. Irreversible electroporation therapy in the liver: longitudinal efficacy studies in a rat model of hepatocellular carcinoma. Cancer Res 2010, 70:1555-1563.
166. Thomas K., Chung W., Ellis S., et al. Investigation of the safety of irreversible electroporation in humans. JVasc Interv Radiol 2011, 22(5):611-621.
167. Hepatocellular carcinoma methods and protocols 2000, Humana Press, Totowa (NJ), [Part IV. HCC gene therapy]. N. Habib (Ed.).
168. Hwang L. Gene therapy strategies for hepatocellular carcinoma. J Biomed Sc 2006, 13:453-486.
169. Wu L., Pan Y., Pei X., et al. Capturing circulating tumor cells of hepatocellular carcinoma. Cancer Let 2012, 10.1016/j.canlet.2012.07.024.
170. Xu W., Cao L., Chen L. Isolation of circulating tumor cells using a novel cell separation strategy. Clin Cancer Res 2011, 17:3783-3793.