Der Gastroenterologe

, Volume 4, Issue 4, pp 301–311

Das hepatozelluläre Karzinom aus der Sicht des Internisten und des Chirurgen

Schwerpunkt
  • 62 Downloads

Zusammenfassung

Das hepatozelluläre Karzinom ist der fünfhäufigste Tumor weltweit und die dritthäufigste Ursache für einen tumorassoziierten Tod. Trotz therapeutischer Fortschritte hat sich das Gesamtüberleben von Patienten mit einem HCC in letzten Jahrzehnten nicht signifikant verbessert. Da die meisten dieser Karzinome auf dem Boden einer Leberzirrhose entstehen, ist nicht nur das Tumorstadium, sondern auch die Leberfunktion für die Wahl der Therapie ausschlaggebend. Je nach Stadium der Erkrankung werden chirurgische und nichtchirurgische Verfahren wie die lokalablative Therapie, die transarterielle Chemotherapie und die Gabe von Sorafenib in kurativer oder palliativer Intention angewandt. Eine Reihe von neuen Therapiestrategien werden derzeit in klinischen Studien evaluiert, u. a. zielgerichtete molekulare Medikamente, die selektive interne Radiotherapie. Da bei den meisten HCC-Patienten auch nach erfolgreicher chirurgischer bzw. nichtchirurgischer Therapie das HCC-Risiko aufgrund der koexistierenden Leberzirrhose weiter besteht, kommt der Sekundärprävention des HCC-Rezidivs bzw. der HCC-Neuentstehung besondere Bedeutung zu. Neben der Exploration neuer therapeutischer und sekundärpräventiver Maßnahmen sowie der HCC-Früherkennung durch Screeningprogramme sollten in der Praxis die bereits bestehenden Möglichkeiten zur Primärprävention der HCC-Entwicklung konsequent implementiert werden.

Schlüsselworte

Hepatozelluläres Karzinom Diagnose Lebertransplantation Lokalablative Therapie Prävention 

Hepatocellular carcinoma from the internist’s and the surgeon’s point of view

Abstract

Hepatocellular carcinoma (HCC) is the 5th most common cancer in the world and the 3rd cause of cancer-related death. Despite therapeutic advances, the overall survival of patients with HCC has not significantly improved in the last decades. Because in the majority of patients HCCs develop in a cirrhotic liver, the patient’s prognosis depends not only on the tumor stage but also on the liver function. Patients at an early stage with an asymptomatic single HCC with a maximum diameter of 5 cm or up to three nodules each less than 3 cm may benefit from curative therapies, including resection, liver transplantation, and percutaneous ablation. Patients exceeding these limits, but who are free of cancer-related symptoms and vascular invasion or extrahepatic spread, may benefit from palliation with chemoembolization. The advanced stage is characterized by mild cancer-related symptoms and/or vascular invasion or extrahepatic spread. Patients at this stage are eligible for treatment with sorafenib; however, a variety of other new drugs, including small molecules and antibodies, are being tested in randomized controlled trials. The development and evaluation of novel HCC treatment strategies as well as the implementation of existing measures and the development of new ones to prevent HCCs are of utmost importance. A better understanding of the clinical and molecular pathogenesis of HCCs should lead to improved diagnostic, therapeutic, and preventive strategies, with the aim to reduce the incidence of HCC, one of the most devastating malignancies worldwide.

Keywords

Hepatocellular carcinoma Diagnosis Liver transplantation Local ablative therapy Prevention 

Literatur

  1. 1.
    (n a) (2000) Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. The Cancer of the Liver Italian Program (CLIP) Investigators. Hepatology 31: 840–845Google Scholar
  2. 2.
    Abou-Alfa Gk, Johnson P, Knox JJ et al (2008) Final results from a phase II randomized, double-blind study of sorafenib plus doxorubicin versus plazebo plus doxorubicin in patients with advanced hepatocellular carcinoma. Gastrointest Cancer Symp Abstr 128Google Scholar
  3. 3.
    Alberts SRMB, Kim GP et al (2007) NCCTG phase II trial (N044 J) of AZD2171 for patients with hepatocellular carcinoma (HCC)-interim review of toxicity. Gastrointestinal Cancer Symposium, Orlando, Fla, Abstract 186Google Scholar
  4. 4.
    Aravalli RN, Steer CJ, Cressman EN (2008) Molecular mechanisms of hepatocellular carcinoma. Hepatology 48: 2047–2063PubMedCrossRefGoogle Scholar
  5. 5.
    Bartolozzi C, Lencioni R, Caramella D et al (1995) Treatment of large HCC: transcatheter arterial chemoembolization combined with percutaneous ethanol injection versus repeated transcatheter arterial chemoembolization. Radiology 197: 812–818PubMedGoogle Scholar
  6. 6.
    Becker G, Soezgen T, Olschewski M et al (2005) Combined TACE and PEI for palliative treatment of unresectable hepatocellular carcinoma. World J Gastroenterol 11: 6104–6109PubMedGoogle Scholar
  7. 7.
    Bosch Fx, Ribes J, Diaz M et al (2004) Primary liver cancer: worldwide incidence and trends. Gastroenterology 127: S5–S16PubMedCrossRefGoogle Scholar
  8. 8.
    Bosetti C, Levi F, Boffetta P et al (2008) Trends in mortality from hepatocellular carcinoma in Europe, 1980-2004. Hepatology 48: 137–145PubMedCrossRefGoogle Scholar
  9. 9.
    Boucher E, Corbinais S, Rolland Y et al (2003) Adjuvant intra-arterial injection of iodine-131-labeled lipiodol after resection of hepatocellular carcinoma. Hepatology 38: 1237–1241PubMedCrossRefGoogle Scholar
  10. 10.
    Boucher E, Jouanolle H, Andre P et al (1995) Interferon and ursodeoxycholic acid combined therapy in the treatment of chronic viral C hepatitis: results from a controlled randomized trial in 80 patients. Hepatology 21: 322–327PubMedGoogle Scholar
  11. 11.
    Brechot C (2004) Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. Gastroenterology 127: S56–S61PubMedCrossRefGoogle Scholar
  12. 12.
    Bruix J, Boix L, Sala M et al (2004) Focus on hepatocellular carcinoma. Cancer Cell 5: 215–219PubMedCrossRefGoogle Scholar
  13. 13.
    Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42: 1208–1236PubMedCrossRefGoogle Scholar
  14. 14.
    Bush DA, Hillebrand DJ, Slater JM et al (2004) High-dose proton beam radiotherapy of hepatocellular carcinoma: preliminary results of a phase II trial. Gastroenterology 127: S189–S193PubMedCrossRefGoogle Scholar
  15. 15.
    Butterfield LH (2007) Recent advances in immunotherapy for hepatocellular cancer. Swiss Med Wkly 137: 83–90PubMedGoogle Scholar
  16. 16.
    Calle EE, Rodriguez C, Walker-Thurmond K et al (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348: 1625–1638PubMedCrossRefGoogle Scholar
  17. 17.
    Chen CJ, Chen DS (2002) Interaction of hepatitis B virus, chemical carcinogen, and genetic susceptibility: multistage hepatocarcinogenesis with multifactorial etiology. Hepatology 36: 1046–1049PubMedCrossRefGoogle Scholar
  18. 18.
    Chen MS, Li JQ, Zheng Y et al (2006) A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg 243: 321–328PubMedCrossRefGoogle Scholar
  19. 19.
    Cheng BQ, Jia CQ, Liu CT et al (2008) Chemoembolization combined with radiofrequency ablation for patients with hepatocellular carcinoma larger than 3 cm: a randomized controlled trial. Jama 299: 1669–1677PubMedCrossRefGoogle Scholar
  20. 20.
    Cho YK, Kim JK, Kim MY et al (2009) Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology 49: 453–459PubMedCrossRefGoogle Scholar
  21. 21.
    Decaens T, Roudot-Thoraval F, Hadni-Bresson S et al (2006) Impact of UCSF criteria according to pre- and post-OLT tumor features: analysis of 479 patients listed for HCC with a short waiting time. Liver Transpl 12: 1761–1769PubMedCrossRefGoogle Scholar
  22. 22.
    Duffy JP, Vardanian A, Benjamin E et al (2007) Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg 246: 502–509; discussion 509–511PubMedCrossRefGoogle Scholar
  23. 23.
    Dufour JF, Huber O, Kozma Sc et al (2007) Tumour suppressors in liver carcinogenesis. J Hepatol 47: 860–867PubMedCrossRefGoogle Scholar
  24. 24.
    El-Serag Hb (2004) Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 127: S27–S34PubMedCrossRefGoogle Scholar
  25. 25.
    El-Serag HB, Davila JA, Petersen NJ et al (2003) The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 139: 817–823PubMedGoogle Scholar
  26. 26.
    El-Serag HB, Rudolph KI (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132: 2557–2576PubMedCrossRefGoogle Scholar
  27. 27.
    Faivre S, Ramiond E, Douillard J (2007) Assessment of safety and drug-induced tumor necrosis with sunitinib in patients with unresectable HCC. J Clin Oncol 25: A4637Google Scholar
  28. 28.
    Farazi PA, Depinho RA (2006) Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 6: 674–687PubMedCrossRefGoogle Scholar
  29. 29.
    Finn RS, Kang Y, Park J et al (2009) Phase II, open label stud of brivanib alaninate in patients with hepatocellular carcinoma who failed prior antiangiogenic therapy. 2009 Gastrointest Cancers Symp Abstr: 200Google Scholar
  30. 30.
    Fuss M, Salter BJ, Herman TS et al (2004) External beam radiation therapy for hepatocellular carcinoma: potential of intensity-modulated and image-guided radiation therapy. Gastroenterology 127: S206–S217PubMedCrossRefGoogle Scholar
  31. 31.
    Geissler M, Mohr L, Ali MY et al (2003) Immunobiology and gene-based immunotherapy of hepatocellular carcinoma. Z Gastroenterol 41: 1101–1110PubMedCrossRefGoogle Scholar
  32. 32.
    Geschwind JF, Salem R, Carr BI et al (2004) Yttrium-90 microspheres for the treatment of hepatocellular carcinoma. Gastroenterology 127: S194–S205PubMedCrossRefGoogle Scholar
  33. 33.
    Ghobrial RM, Freise CE, Trotter JF et al (2008) Donor morbidity after living donation for liver transplantation. Gastroenterology 135: 468–476PubMedCrossRefGoogle Scholar
  34. 34.
    Greten TF, Korangy F, Manns MP et al (2009) Molecular therapy for the treatment of hepatocellular carcinoma. Br J Cancer 100: 19–23PubMedCrossRefGoogle Scholar
  35. 35.
    Gruenwald V, Wilkens L, Gebel M (2007) A phase II open-label study of cetuximab in unresectable hepatocellular carcinom: final results. J Clin Oncol 25: A4594Google Scholar
  36. 36.
    Gurusamy KS, Pamecha V, Sharma D et al (2009) Techniques for liver parenchymal transection in liver resection. Cochrane Database Syst Rev CD006880Google Scholar
  37. 37.
    Hassan MM, Hwang LY, Hatten CJ et al (2002) Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology 36: 1206–1213PubMedCrossRefGoogle Scholar
  38. 38.
    Hsu C, Yang T, Hsu C et al (2007) Modified-dose capecitabine+bevacizumab for the treatment of advanced/metastatic hepatocellular carcinoma: a phase II, single-arm study. J Clin Oncol 25: 15190CrossRefGoogle Scholar
  39. 39.
    Huang GT, Lee PH, Tsang YM et al (2005) Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg 242: 36–42PubMedCrossRefGoogle Scholar
  40. 40.
    Ikeda K, Arase Y, Saitoh S et al (2000) 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 32: 228–232PubMedCrossRefGoogle Scholar
  41. 41.
    Jolesz FA, Hynynen K, Mcdannold N et al (2004) Noninvasive thermal ablation of hepatocellular carcinoma by using magnetic resonance imaging-guided focused ultrasound. Gastroenterology 127: S242–S247PubMedCrossRefGoogle Scholar
  42. 42.
    Kamada K, Kitamoto M, Aikata H et al (2002) Combination of transcatheter arterial chemoembolization using cisplatin-lipiodol suspension and percutaneous ethanol injection for treatment of advanced small hepatocellular carcinoma. Am J Surg 184: 284–290PubMedCrossRefGoogle Scholar
  43. 43.
    Koch I, Baron A, Roberts S (2005) Influence of hepatic dysfunction on safety, tolerability and pharmacocinetics of PTK787/ZK222584 in patients with unresectable HCC. J Clin Oncol 23: A4134CrossRefGoogle Scholar
  44. 44.
    Koda M, Murawaki Y, Mitsuda A et al (2001) Combination therapy with transcatheter arterial chemoembolization and percutaneous ethanol injection compared with percutaneous ethanol injection alone for patients with small hepatocellular carcinoma: a randomized control study. Cancer 92: 1516–1524PubMedCrossRefGoogle Scholar
  45. 45.
    Kulik LM, Atassi B, Van Holsbeeck L et al (2006) Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation. J Surg Oncol 94: 572–586PubMedCrossRefGoogle Scholar
  46. 46.
    Kulik LM, Carr BI, Mulcahy MF et al (2008) Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology 47: 71–81PubMedCrossRefGoogle Scholar
  47. 47.
    Lang H, Sotiropoulos GC, Domland M et al (2005) Liver resection for hepatocellular carcinoma in non-cirrhotic liver without underlying viral hepatitis. Br J Surg 92: 198–202PubMedCrossRefGoogle Scholar
  48. 48.
    Lau WY, Leung TW, Ho SK et al (1999) Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial. Lancet 353: 797–801PubMedCrossRefGoogle Scholar
  49. 49.
    Lencioni R, Crocetti L (2005) A critical appraisal of the literature on local ablative therapies for hepatocellular carcinoma. Clin Liver Dis 9: 301–314PubMedCrossRefGoogle Scholar
  50. 50.
    Lencioni RA, Allgaier HP, Cioni D et al (2003) Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology 228: 235–240PubMedCrossRefGoogle Scholar
  51. 51.
    Lin SM, Lin CJ, Lin CC et al (2004) Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma <or =4 cm. Gastroenterology 127: 1714–1723PubMedCrossRefGoogle Scholar
  52. 52.
    Lin SM, Lin CJ, Lin CC et al (2005) 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 54: 1151–1156PubMedCrossRefGoogle Scholar
  53. 53.
    Livraghi T, Meloni F, Di Stasi M et al (2008) Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice? Hepatology 47: 82–89PubMedCrossRefGoogle Scholar
  54. 54.
    Llovet JM, Bru C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19: 329–338PubMedCrossRefGoogle Scholar
  55. 55.
    Llovet JM, Bruix J (2008) Molecular targeted therapies in hepatocellular carcinoma. Hepatology 48: 1312–1327PubMedCrossRefGoogle Scholar
  56. 56.
    Llovet JM, Bruix J (2008) Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol 48 (Suppl 1): S20–S37PubMedCrossRefGoogle Scholar
  57. 57.
    Llovet JM, Bruix J (2004) Unresectable hepatocellular carcinoma: meta-analysis of arterial embolization. Radiology 230: 300–301; author reply 301–302PubMedCrossRefGoogle Scholar
  58. 58.
    Llovet JM, Real MI, Montana X et al (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359: 1734–1739PubMedCrossRefGoogle Scholar
  59. 59.
    Llovet JM, Ricci S, Mazzaferro V et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: 378–390PubMedCrossRefGoogle Scholar
  60. 60.
    Llovet JM, Schwartz M, Mazzaferro V (2005) Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 25: 181–200PubMedCrossRefGoogle Scholar
  61. 61.
    Louafi S, Hebbar M, Rosmorduc O (2007) Gemcitabine, oxalaplatin and cetuximab for treatment of hepatocellular carcinoma: rsults of phase II study ERGO. J Clin Oncol 18SGoogle Scholar
  62. 62.
    Lubrano J, Huet E, Tsilividis B et al (2008) Long-term outcome of liver resection for hepatocellular carcinoma in noncirrhotic nonfibrotic liver with no viral hepatitis or alcohol abuse. World J Surg 32: 104–109PubMedCrossRefGoogle Scholar
  63. 63.
    Malka D, Dromain C, Farace F et al (2007) Bevacizumab in patients with advanced hepatocellular carcinoma: preliminary results of a phase II study with circulating endothelial cell monitoring. J Clin Oncol 25: 4570Google Scholar
  64. 64.
    Mazzaferro V, Regalia E, Doci R et al (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334: 693–699PubMedCrossRefGoogle Scholar
  65. 65.
    Ming L, Thorgeirsson SS, Gail MH et al (2002) Dominant role of hepatitis B virus and cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China. Hepatology 36: 1214–1220PubMedCrossRefGoogle Scholar
  66. 66.
    Mishra L, Banker T, Murray J et al (2009) Liver stem cells and hepatocellular carcinoma. Hepatology 49: 318–329PubMedCrossRefGoogle Scholar
  67. 67.
    Mohr L, Shankara S, Yoon SK et al (2000) Gene therapy of hepatocellular carcinoma in vitro and in vivo in nude mice by adenoviral transfer of the Escherichia coli purine nucleoside phosphorylase gene. Hepatology 31: 606–614PubMedCrossRefGoogle Scholar
  68. 68.
    Mohr L, Yeung A, Aloman C et al (2004) Antibody-directed therapy for human hepatocellular carcinoma. Gastroenterology 127: S225–S231PubMedCrossRefGoogle Scholar
  69. 69.
    Mulier S, Ruers T, Jamart J et al (2008) Radiofrequency ablation versus resection for resectable colorectal liver metastases: time for a randomized trial? An update. Dig Surg 25: 445–460PubMedCrossRefGoogle Scholar
  70. 70.
    Muto Y, Moriwaki H, Ninomiya M et al (1996) Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group. N Engl J Med 334: 1561–1567PubMedCrossRefGoogle Scholar
  71. 71.
    Nakamoto Y, Guidotti L, Kuhlen C et al (1998) Immune pathogenesis of hepatocellular carcinoma. J Exp Med 188: 341–350PubMedCrossRefGoogle Scholar
  72. 72.
    Nakamoto Y, Kaneko S, Fan H et al (2002) Prevention of hepatocellular carcinoma development associated with chronic hepatitis by anti-fas ligand antibody therapy. J Exp Med 196: 1105–1111PubMedCrossRefGoogle Scholar
  73. 73.
    Neeff H, Makowiec F, Harder J et al (2009) Hepatic resection for hepatocellular carcinoma - results and analysis of the current literature. Zentralbl Chir 134: 127–135PubMedCrossRefGoogle Scholar
  74. 74.
    O‘Dwyer PJ, Giantonio BJ, Levy DE et al (2006) Gefitinib in advanced unresectable hepatocellular carcinoma: results from the Eastern Cooperative Oncology Groups‘s study E1203. J Clin Oncol 24: A4143CrossRefGoogle Scholar
  75. 75.
    O‘Neil BH, Bernard SA, Goldberg RM et al (2008) Phase II study of oxaliplatin, capecitabine, and cetuximab in advanced hepatocellular carcinoma. J Clin Oncol 26Google Scholar
  76. 76.
    Okuda K, Ohtsuki T, Obata H et al (1985) Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 56: 918–928PubMedCrossRefGoogle Scholar
  77. 77.
    Ozturk M (1999) Genetic aspects of hepatocellular carcinogenesis. Semin Liver Dis 19: 235–242PubMedCrossRefGoogle Scholar
  78. 78.
    Pei Z, Chu L, Zou W et al (2004) An oncolytic adenoviral vector of Smac increases antitumor activity of TRAIL against HCC in human cells and in mice. Hepatology 39: 1371–1381PubMedCrossRefGoogle Scholar
  79. 79.
    Philip PA, Mahoney MR, Allmer C et al (2005) Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer. J Clin Oncol 23: 6657–6663PubMedCrossRefGoogle Scholar
  80. 80.
    Pollicino T, Squadrito G, Cerenzia G et al (2004) Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology 126: 102–110PubMedCrossRefGoogle Scholar
  81. 81.
    Ramanathan RK, Belani CP, Singh DA (2006) Phase II study of lapatinib, a dual inhibitor of epidermal growth factor receptor tyrosine kinase 1 and 2 (Her2/Neu) in patients with advanced biliary tree cancer or hepatocellular carcinoma. J Clin Oncol 24: A4010Google Scholar
  82. 82.
    Ribes J, Cleries R, Esteban L et al (2008) The influence of alcohol consumption and hepatitis B and C infections on the risk of liver cancer in Europe. J Hepatol 49: 233–242PubMedCrossRefGoogle Scholar
  83. 83.
    Risse JH, Grunwald F, Kersjes W et al (2000) Intraarterial HCC therapy with I-131-Lipiodol. Cancer Biother Radiopharm 15: 65–70PubMedCrossRefGoogle Scholar
  84. 84.
    Satyanarayana A, Manns MP, Rudolph KI (2004) Telomeres and telomerase: a dual role in hepatocarcinogenesis. Hepatology 40: 276–283PubMedCrossRefGoogle Scholar
  85. 85.
    Selle D, Preim B, Schenk A et al (2002) Analysis of vasculature for liver surgical planning. IEEE Trans Med Imaging 21: 1344–1357PubMedCrossRefGoogle Scholar
  86. 86.
    Seyama Y, Kokudo N (2009) Assessment of liver function for safe hepatic resection. Hepatol Res 39: 107–116PubMedCrossRefGoogle Scholar
  87. 87.
    Sherman M, Klein A (2004) AASLD single-topic research conference on hepatocellular carcinoma: Conference proceedings. Hepatology 40: 1465–1473PubMedCrossRefGoogle Scholar
  88. 88.
    Shibata T, Iimuro Y, Yamamoto Y et al (2002) Small hepatocellular carcinoma: comparison of radio-frequency ablation and percutaneous microwave coagulation therapy. Radiology 223: 331–337PubMedCrossRefGoogle Scholar
  89. 89.
    Shiina S, Teratani T, Obi S et al (2005) A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology 129: 122–130PubMedCrossRefGoogle Scholar
  90. 90.
    Shinozaki K, Ebert O, Woo Sl (2005) Eradication of advanced hepatocellular carcinoma in rats via repeated hepatic arterial infusions of recombinant VSV. Hepatology 41: 196–203PubMedCrossRefGoogle Scholar
  91. 91.
    Siegel AB, Cohen EI, Ocean A et al (2008) Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol 26: 2992–2998PubMedCrossRefGoogle Scholar
  92. 92.
    Song TJ, Ip EW, Fong Y (2004) Hepatocellular carcinoma: current surgical management. Gastroenterology 127: S248–S260PubMedCrossRefGoogle Scholar
  93. 93.
    Spangenberg HC, Thimme R, Blum He (2006) Serum markers of hepatocelllar carcinoma. Semin Lver Dis 26: 385–390CrossRefGoogle Scholar
  94. 94.
    Stefani Al, Barzon L, Castagliuolo I et al (2005) Systemic efficacy of combined suicide/cytokine gene therapy in a murine model of hepatocellular carcinoma. J Hepatol 42: 728–735PubMedCrossRefGoogle Scholar
  95. 95.
    Sun W, Haller DG, Mykulowycz K et al (2007) Combination of capecitabine, oxaliplatin with bevacizumab in treatment of advanced hepatocellular carcinoma: a phase II study. J Clin Oncol 25Google Scholar
  96. 96.
    Suriawinata A, Xu R (2004) An update on the molecular genetics of hepatocellular carcinoma. Semin Liver Dis 24: 77–88PubMedCrossRefGoogle Scholar
  97. 97.
    Takayama T, Sekine T, Makuuchi M et al (2000) Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet 356: 802–807PubMedCrossRefGoogle Scholar
  98. 98.
    Taketomi A, Soejima Y, Yoshizumi T et al (2008) Liver transplantation for hepatocellular carcinoma. J Hepatobiliary Pancreat Surg 15: 124–130PubMedCrossRefGoogle Scholar
  99. 99.
    Tanaka K, Okazaki H, Nakamura S et al (1991) Hepatocellular carcinoma: treatment with a combination therapy of transcatheter arterial embolization and percutaneous ethanol injection. Radiology 179: 713–717PubMedGoogle Scholar
  100. 100.
    Tanaka S, Arii S (2009) Molecularly targeted therapy for hepatocellular carcinoma. Cancer Sci 100: 1–8PubMedCrossRefGoogle Scholar
  101. 101.
    Thomas M, Chadha R, Iwasak M (2007) The combination of bevacizumab and erlotinib shows significant biological activity in patients with advanced HCC. J Clin Oncol 25: A15190Google Scholar
  102. 102.
    Thomas MB, Chadha R, Glover K et al (2007) Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma. Cancer 110: 1059–1067PubMedCrossRefGoogle Scholar
  103. 103.
    Thorgeirsson SS, Grisham JW (2002) Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 31: 339–346PubMedCrossRefGoogle Scholar
  104. 104.
    Van Gulik TM, Adam R (2008) Controversies in the management of liver metastases. Dig Surg 25: 405CrossRefGoogle Scholar
  105. 105.
    Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46: 474–481PubMedCrossRefGoogle Scholar
  106. 106.
    Velazquez RF, Rodriguez M, Navascues CA et al (2003) Prospective analysis of risk factors for hepatocellular carcinoma in patients with liver cirrhosis. Hepatology 37: 520–527PubMedCrossRefGoogle Scholar
  107. 107.
    Villanueva A, Newell P, Chiang DY et al (2007) Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis 27: 55–76PubMedCrossRefGoogle Scholar
  108. 108.
    Watanabe J, Minegishi K, Mitsumori T et al (1990) Prevalence of anti-HCV antibody in blood donors in the Tokyo area. Vox Sang 59: 86–88PubMedCrossRefGoogle Scholar
  109. 109.
    Wu F, Wang ZB, Chen WZ et al (2005) Advanced hepatocellular carcinoma: treatment with high-intensity focused ultrasound ablation combined with transcatheter arterial embolization. Radiology 235: 659–667PubMedCrossRefGoogle Scholar
  110. 110.
    Yamamoto K, Masuzawa M, Kato M et al (1997) Evaluation of combined therapy with chemoembolization and ethanol injection for advanced hepatocellular carcinoma. Semin Oncol 24 (Suppl 6): 50–55Google Scholar
  111. 111.
    Yano Y, Yamashita F, Sumie S et al (2002) Clinical features of hepatocellular carcinoma seronegative for both HBsAg and anti-HCV antibody but positive for anti-HBc antibody in Japan. Am J Gastroenterol 97: 156–161PubMedCrossRefGoogle Scholar
  112. 112.
    Yu MC, Yuan JM (2004) Environmental factors and risk for hepatocellular carcinoma. Gastroenterology 127: S72–S78PubMedCrossRefGoogle Scholar
  113. 113.
    Yu SC, Hui JW, Hui EP et al (2009) Embolization efficacy and treatment effectiveness of transarterial therapy for unresectable hepatocellular carcinoma: a case-controlled comparison of transarterial ethanol ablation with lipiodol-ethanol mixture versus transcatheter arterial chemoembolization. J Vasc Interv Radiol 20: 352–359PubMedCrossRefGoogle Scholar
  114. 114.
    Zhu AX, Blaszkowsky LS, Ryan DP et al (2006) Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma. J Clin Oncol 24: 1898–1903PubMedCrossRefGoogle Scholar
  115. 115.
    Zhu AX, Sahani D, Di Tomasi E (2007) A phase II study of sutininib in patients with advanced HCC. J Clin Oncol 25: A4637Google Scholar
  116. 116.
    Zhu AX, Stuart K, Blaszkowsky LS et al (2007) Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma. Cancer 110: 581–589PubMedCrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag 2009

Authors and Affiliations

  • H.C. Spangenberg
    • 1
  • O. Drognitz
    • 2
  • R. Thimme
    • 1
  • U. Hopt
    • 2
  1. 1.Abteilung Innere Medizin II, Medizinische UniversitätsklinikAlbert-Ludwigs-Universität FreiburgFreiburgDeutschland
  2. 2.Abteilung Allgemein- und ViszeralchirurgieAlbert-Ludwigs-Universität FreiburgFreiburgDeutschland

Personalised recommendations