Download PDF
Semin Liver Dis 2005; 25(2): 181-200
DOI: 10.1055/s-2005-871198
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Resection and Liver Transplantation for Hepatocellular Carcinoma

Josep M. Llovet1 , 2 , Myron Schwartz2 , Vincenzo Mazzaferro3
  • 1Senior Researcher, BCLC Group, Liver Unit, Digestive Disease Institute, IDIBAPS, Hospital Clínic, University of Barcelona, Catalonia, Spain
  • 2Division of Liver Diseases and Recanati Miller Transplantation Institute, Mount Sinai School of Medicine, New York, New York
  • 3G.I. Surgery and Liver Transplantation Unit, National Cancer Institute, Milan, Italy
Further Information

Publication History

Publication Date:
25 May 2005 (online)

    Permissions and Reprints

ABSTRACT

Surveillance programs in cirrhotic patients enable the detection of hepatocellular carcinoma (HCC) at early stages, when the tumor is amenable to curative treatments (60% of cases in Japan; 25 to 40% in Europe and the United States). Resection is the mainstay of treatment in noncirrhotic patients and in cirrhotics with well-preserved liver function. In modern series, a perioperative mortality ≤ 3% and 5-year survival rates above 50% are expected. Tumor recurrence complicates half of the cases at 3 years, but there is no unquestionable preventive treatment. Liver transplantation provides excellent outcomes applying the Milan criteria (single nodule ≤ 5 cm or two or three nodules ≤ 3 cm), with 5-year survival rates of 70% and low recurrence rates. Although expansion of selection criteria is appealing, it should be assessed in the setting of prospective well-designed studies. Intention-to-treat analysis has shown that wide extended indications lead to 25% 5-year survival rates. Living donor liver transplantation is having a minor impact in HCC management. Molecular markers are needed to better select the candidates for surgery.

KEYWORDS

Hepatocellular carcinoma - resection - liver transplantation - living donor liver transplantation - adjuvant treatments

REFERENCES

  • 1 Parkin D M, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: GLOBOCAN 2000.  Int J Cancer. 2001;  94 153-156
    CrossrefPubMedSearch in Google Scholar
  • 2 El-Serag H B, Mason A C. Rising incidence of hepatocellular carcinoma in the United States.  N Engl J Med. 1999;  340 745-750
    CrossrefPubMedSearch in Google Scholar
  • 3 Bosch F X, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends.  Gastroenterology. 2004;  127 S5-S16
    CrossrefPubMedSearch in Google Scholar
  • 4 Sangiovanni A, Del Ninno E, Fasani P et al.. Increased survival of cirrhotic patients with hepatocellular carcinoma detected during surveillance.  Gastroenterology. 2004;  126 1005-1014
    CrossrefPubMedSearch in Google Scholar
  • 5 Llovet J M, Burroughs A, Bruix J. Hepatocellular carcinoma.  Lancet. 2003;  362 1907-1917
    CrossrefPubMedSearch in Google Scholar
  • 6 Bruix J, Sherman M, Llovet J M et al.. Clinical management of hepatocellular carcinoma: conclusions of the Barcelona-2000 EASL conference.  J Hepatol. 2001;  35 421-430
    CrossrefPubMedSearch in Google Scholar
  • 7 Llovet J M, Bustamante J, Castells A et al.. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials.  Hepatology. 1999;  29 62-67
    CrossrefPubMedSearch in Google Scholar
  • 8 Villa E, Moles A, Ferretti I et al.. Natural history of inoperable hepatocellular carcinoma: estrogen receptors’ status in the tumor is the strongest prognostic factor for survival.  Hepatology. 2000;  32 233-238
    CrossrefPubMedSearch in Google Scholar
  • 9 Takayama T, Makuuchi S, Hirohashi S et al.. Early hepatocellular carcinoma as an entity with high rate of surgical cure.  Hepatology. 1998;  28 1241-1246
    CrossrefPubMedSearch in Google Scholar
  • 10 Fong Y, Sun R L, Jarnagin W, Blumgart L H. An analysis of 412 cases of hepatocellular carcinoma at a Western center.  Ann Surg. 1999;  229 790-799
    CrossrefPubMedSearch in Google Scholar
  • 11 Llovet J M, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation.  Hepatology. 1999;  30 1434-1440
    CrossrefPubMedSearch in Google Scholar
  • 12 Arii S, Yamaoka Y, Futagawa S et al.. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan.  Hepatology. 2000;  32 1224-1229
    CrossrefPubMedSearch in Google Scholar
  • 13 Zhou X D, Tang Z Y, Yang B H et al.. Experience of 1000 patients who underwent hepatectomy for small hepatocellular carcinoma.  Cancer. 2001;  91 1479-1486
    CrossrefPubMedSearch in Google Scholar
  • 14 Poon R T, Fan S T, Lo C M et al.. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation.  Ann Surg. 2002;  235 373-382
    CrossrefPubMedSearch in Google Scholar
  • 15 Wayne J D, Lauwers G Y, Ikai I et al.. Preoperative predictors of survival after resection of small hepatocellular carcinomas.  Ann Surg. 2002;  235 722-731
    CrossrefPubMedSearch in Google Scholar
  • 16 Kianmanesh R, Regimbeau J M, Bekghiti J. Selective approach to major hepatic resection for hepatocellular carcinoma on chronic liver disease.  Surg Oncol Clin N Am. 2003;  12 51-63
    CrossrefPubMedSearch in Google Scholar
  • 17 Ercolani G, Grazi G L, Ravaioli M et al.. Liver resection for hepatocellular carcinoma on cirrhosis.  Ann Surg. 2003;  237 536-543
    CrossrefPubMedSearch in Google Scholar
  • 18 Ikai I, Arii S, Kojiro M et al.. Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey.  Cancer. 2004;  101 796-802
    CrossrefPubMedSearch in Google Scholar
  • 19 Mazzaferro V, Regalia E, Doci R et al.. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.  N Engl J Med. 1996;  334 693-699
    CrossrefPubMedSearch in Google Scholar
  • 20 Bismuth H, Majno P E, Adam R. Liver transplantation for hepatocellular carcinoma.  Semin Liver Dis. 1999;  19 311-322
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 Jonas S, Bechstein W O, Steinmuller T et al.. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis.  Hepatology. 2001;  33 1080-1086
    CrossrefPubMedSearch in Google Scholar
  • 22 Yao F Y, Ferrell L, Bass N M et al.. Liver transplantation for hepatocellular carcinoma: expansion of tumor size limits does not adversely impact survival.  Hepatology. 2001;  33 1394-1403
    CrossrefPubMedSearch in Google Scholar
  • 23 Adam R, Azoulay D, Castaing D et al.. Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy?.  Ann Surg. 2003;  238 508-519
    PubMedSearch in Google Scholar
  • 24 Hemming A W, Nelson D R, Reed A I. Liver transplantation for hepatocellular carcinoma.  Minerva Chir. 2002;  57 575-585
    PubMedSearch in Google Scholar
  • 25 Shetty K, Timmins K, Brensinger C et al.. Liver transplantation for hepatocellular carcinoma validation of present selection criteria in predicting outcome.  Liver Transpl. 2004;  10 911-918
    CrossrefPubMedSearch in Google Scholar
  • 26 Herrero J I, Sangro B, Quiroga J et al.. Influence of tumor characteristics on the outcome of liver transplantation among patients with liver cirrhosis and hepatocellular carcinoma.  Liver Transpl. 2001;  7 631-636
    CrossrefPubMedSearch in Google Scholar
  • 27 Roayaie S, Frischer J, Emre S H et al.. Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 cm.  Ann Surg. 2002;  235 533-539
    CrossrefPubMedSearch in Google Scholar
  • 28 Marsh J W, Dvorchik I. Liver organ allocation for hepatocellular carcinoma: are we sure?.  Liver Transpl. 2003;  9 693-696
    CrossrefPubMedSearch in Google Scholar
  • 29 Molmenti E, Klintmalm G. Liver transplantation in association with hepatocellular carcinoma: an update of the International Tumor Registry.  Liver Transpl. 2002;  8 736-748
    CrossrefPubMedSearch in Google Scholar
  • 30 Cillo U, Vitale A, Bassanello M et al.. Liver transplantation for the treatment of moderately or well-differentiated hepatocellular carcinoma.  Ann Surg. 2004;  239 150-159
    PubMedSearch in Google Scholar
  • 31 National Cancer Institute website, U.S. National Institutes of Health . http://www.cancer.gov
  • 32 Kaihara S, Kiuchi T, Ueda M et al.. Living donor liver transplantation for hepatocellular carcinoma.  Transplantation. 2003;  75 S37-S40
    PubMedSearch in Google Scholar
  • 33 Gondolesi G, Roayaie S, Muñoz L et al.. Adult living donor liver transplantation for patients with hepatocellular carcinoma: extending UNOS priority criteria.  Ann Surg. 2004;  239 142-149
    CrossrefPubMedSearch in Google Scholar
  • 34 Todo S, Furukawa H. Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan.  Ann Surg. 2004;  240 451-461
    CrossrefPubMedSearch in Google Scholar
  • 35 Llovet J M, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival.  Hepatology. 2003;  37 429-442
    CrossrefPubMedSearch in Google Scholar
  • 36 Llovet J M, Real M I, Montaña X et al.. Arterial embolisation or chemoembolization versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial.  Lancet. 2002;  359 1734-1739
    CrossrefPubMedSearch in Google Scholar
  • 37 Belghiti J, Hiramatsu K, Benoist S. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection.  J Am Coll Surg. 2000;  191 38-46
    CrossrefPubMedSearch in Google Scholar
  • 38 Bralet M P, Regimbeau J M, Pineau P et al.. Hepatocellular carcinoma occurring in nonfibrotic liver: epidemiologic and histopathologic analysis of 80 French cases.  Hepatology. 2000;  32 200-204
    CrossrefPubMedSearch in Google Scholar
  • 39 Bismuth H, Majno P E. Hepatobiliary surgery.  J Hepatol. 2000;  32(1 suppl) 208-224
    PubMedSearch in Google Scholar
  • 40 Song T, Ip E, Fong Y. Hepatocellular carcinoma: current surgical management.  Gastroenterology. 2004;  127 S248-S260
    PubMedSearch in Google Scholar
  • 41 Marin-Hargreaves G, Azoulay D, Bismuth H. Hepatocellular carcinoma: surgical indications and results.  Crit Rev Oncol Hematol. 2003;  47 13-27
    CrossrefPubMedSearch in Google Scholar
  • 42 Makuuchi M, Sano K. The surgical approach to HCC: our progress and results in Japan.  Liver Transpl. 2004;  10 S46-S52
    CrossrefPubMedSearch in Google Scholar
  • 43 Torzilli G, Makuuchi M, Inoue K et al.. No-mortality liver resection for hepatocellular carcinoma in cirrhotic and noncirrhotic patients: is there a way? A prospective analysis of our approach.  Arch Surg. 1999;  134 984-992
    PubMedSearch in Google Scholar
  • 44 Fan S T, Lo C M, Liu C L et al.. Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths.  Ann Surg. 1999;  229 322-330
    CrossrefPubMedSearch in Google Scholar
  • 45 Sobin LH, Wittekind C TNM Classification of Malignant Tumors. 5th ed. New York; John Wiley & Sons 1997
  • 46 Liver (including intrahepatic bile ducts) .In: Green F, Page D, Fleming I, et al AJCC Cancer Staging Handbook. 6th ed. New York; Springer 2002: 131-144
    Search in Google Scholar
  • 47 Izumi R, Shimizu K, Ii T et al.. Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection.  Gastroenterology. 1994;  106 720-727
    PubMedSearch in Google Scholar
  • 48a Llovet J M, Bruix J, Fuster J et al.. Liver transplantation for treatment of small hepatocellular carcinoma: the TNM classification does not have prognostic power.  Hepatology. 1998;  27 1572-1577
    CrossrefPubMedSearch in Google Scholar
  • 48b Sala M, Forner A, Varela M, Bruix J. Prognostic prediction in patients with hepatocellular carcinoma.  Semin Liver Dis. 2005;  25 171-180
    Thieme ConnectPubMedSearch in Google Scholar
  • 49 Llovet J M, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification.  Semin Liver Dis. 1999;  19 329-338
    Thieme ConnectPubMedSearch in Google Scholar
  • 50 Befeler A S, Di Bisceglie A M. Hepatocellular carcinoma: diagnosis and treatment.  Gastroenterology. 2002;  122 1609-1619
    PubMedSearch in Google Scholar
  • 51 Marrero J, Fontana R, Barrat A et al.. Prognosis of hepatocellular carcinoma: comparison of seven staging systems in an American cohort.  Hepatology. 2005;  , In press
    PubMedSearch in Google Scholar
  • 52 Vauthey J, Lauwers G, Esnaola N et al.. Simplified staging for hepatocellular carcinoma.  J Clin Oncol. 2002;  20 1527-1536
    CrossrefPubMedSearch in Google Scholar
  • 53 Poon R, Fan S. Evaluation of the new AJCC/UICC staging system for hepatocellular carcinoma after hepatic resection in Chinese patients.  Surg Oncol Clin N Am. 2003;  12 35-50
    CrossrefPubMedSearch in Google Scholar
  • 54 Makuuchi M, Hasegawa H, Yamazaki S. Indication of hepatectomy in patients with hepatocellular carcinoma and cirrhosis.  Shindan to Chiryo (in Japanese). 1986;  74 1225-1230
    PubMedSearch in Google Scholar
  • 55 Miyagawa S, Mackuuchi M, Kawasaki S et al.. Criteria for safe hepatic resection.  Am J Surg. 1995;  169 589-594
    CrossrefPubMedSearch in Google Scholar
  • 56 Poon R, Fan S T. Hepatectomy for hepatocellular carcinoma: patient selection and postoperative outcome.  Liver Transpl. 2004;  10 S39-S45
    PubMedSearch in Google Scholar
  • 57 Bruix J, Castells A, Bosch J et al.. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure.  Gastroenterology. 1996;  111 1018-1022
    CrossrefPubMedSearch in Google Scholar
  • 58 Murakami T, Mochizuki K, Nakamura H. Imaging evaluation of the cirrhotic liver.  Semin Liver Dis. 2001;  21 213-224
    Thieme ConnectPubMedSearch in Google Scholar
  • 59 Rizzi P M, Kane P A, Ryder S D et al.. Accuracy of radiology in detection of hepatocellular carcinoma before liver transplantation.  Gastroenterology. 1994;  107 1425-1429
    PubMedSearch in Google Scholar
  • 60 De Carlis L, Giacomoni A, Pirotta V et al.. Surgical treatment of hepatocellular cancer in the era of hepatic transplantation.  J Am Coll Surg. 2003;  196 887-897
    CrossrefPubMedSearch in Google Scholar
  • 61 Burrel M, Llovet J M, Ayuso C et al.. MRI angiography is superior to helical CT for detection of HCC prior to liver transplantation: an explant correlation.  Hepatology. 2003;  38 1034-1042
    CrossrefPubMedSearch in Google Scholar
  • 62 Torzilli G, Olivari N, Moroni E et al.. Contrast-enhanced intraoperative ultrasonography in surgery for hepatocellular carcinoma in cirrhosis.  Liver Transpl. 2004;  10 S34-S38
    CrossrefPubMedSearch in Google Scholar
  • 63 Llovet J M, Wurmbach E. Gene expression profile in hepatocellular carcinoma: not yet there.  J Hepatol. 2004;  41 336-339
    CrossrefPubMedSearch in Google Scholar
  • 64 Makuuchi M, Belghiti J B, Belli G et al.. IHPBA concordant classification of primary liver cancer: working group report.  J Hepatobiliary Pancreat Surg. 2003;  10 26-30
    PubMedSearch in Google Scholar
  • 65 Kojiro M. Focus on dysplastic nodules and early hepatocellular carcinoma: an eastern point of view.  Liver Transpl. 2004;  10 S3-S8
    CrossrefPubMedSearch in Google Scholar
  • 66 Sakamoto M, Hirohashi S. Natural history and prognosis of adenomatous hyperplasia and early hepatocellular carcinoma: multi-institutional analysis of 53 nodules followed up for more than 6 months and 141 patients with single early hepatocellular carcinoma treated by surgical resection or percutaneous ethanol injection.  Jpn J Clin Oncol. 1998;  28 604-608
    CrossrefPubMedSearch in Google Scholar
  • 67 Lee J, Chu I, Heo J et al.. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling.  Hepatology. 2004;  40 667-676
    CrossrefPubMedSearch in Google Scholar
  • 68 Belghiti J, Panis Y, Farges O et al.. Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis.  Ann Surg. 1991;  214 114-117
    CrossrefPubMedSearch in Google Scholar
  • 69 Okada S, Shimada K, Yamamoto J et al.. Predictive factors for postoperative recurrence of hepatocellular carcinoma.  Gastroenterology. 1994;  106 1618-1624
    PubMedSearch in Google Scholar
  • 70 Adachi E, Maeda T, Matsumata T et al.. Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma.  Gastroenterology. 1995;  108 768-775
    CrossrefPubMedSearch in Google Scholar
  • 71 Kumada T, Nakano S, Takeda I et al.. Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma.  Hepatology. 1997;  25 87-92
    PubMedSearch in Google Scholar
  • 72 Imamura H, Matsuyama Y, Tanaka E et al.. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy.  J Hepatol. 2003;  38 200-207
    PubMedSearch in Google Scholar
  • 73 Iizuka N, Oka M, Yamada-Okabe H et al.. Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma after curative resection.  Lancet. 2003;  361 923-929
    CrossrefPubMedSearch in Google Scholar
  • 74 Chen Y, Yeh S H, Chen J T et al.. Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma.  Gastroenterology. 2000;  119 431-440
    PubMedSearch in Google Scholar
  • 75 Finkelstein S D, Marsh W, Demetris A J et al.. Microdissection-based allelotyping discriminates de novo tumor from intrahepatic spread in hepatocellular carcinoma.  Hepatology. 2003;  37 871-879
    CrossrefPubMedSearch in Google Scholar
  • 76 Ng I, Guan X, Poon R et al.. Determination of the molecular relationship between multiple tumor nodules in hepatocellular carcinoma differentiates multicentric origin from intrahepatic metastasis.  J Pathol. 2003;  199 345-353
    CrossrefPubMedSearch in Google Scholar
  • 77 Muto Y, Moriwaki H, Ninomiya M, Adachi S, Saito A, Takasaki K T. Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma.  N Engl J Med. 1996;  334 1561-1567
    CrossrefPubMedSearch in Google Scholar
  • 78 Schwartz J D, 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
    CrossrefPubMedSearch in Google Scholar
  • 79 Wu C C, Oho Y Z, Lin W et al.. Preoperative transcatheter arterial chemoembolization for resectable large hepatocellular carcinoma: a reappraisal.  Br J Surg. 1995;  82 122-126
    CrossrefPubMedSearch in Google Scholar
  • 80 Yamasaki S, Hasegawa H, Kinoshita H et al.. A prospective randomized trial of preventive effect of pre-operative transcatheter arterial embolization against recurrence of hepatocellular carcinoma.  Jpn J Cancer Res. 1996;  87 206-211
    PubMedSearch in Google Scholar
  • 81 Izumi R, Shimizu S, Iyobe T et al.. Postoperative adjuvant hepatic arterial infusion of lipiodol containing anticancer drugs in patients with hepatocellular carcinoma.  Hepatology. 1994;  20 295-301
    CrossrefPubMedSearch in Google Scholar
  • 82 Li J Q, Zhang Y K, Zhang W Z et al.. Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy.  J Cancer Res Clin Oncol. 1995;  121 364-366
    CrossrefPubMedSearch in Google Scholar
  • 83 Lai E C, Lo C M, Fan S T et al.. Postoperative adjuvant chemotherapy after curative resection of hepatocellular carcinoma.  Arch Surg. 1998;  133 183-188
    PubMedSearch in Google Scholar
  • 84 Ueno S, Tanabe G, Yoshida K et al.. Postoperative prediction and strategy for metastatic recurrent hepatocellular carcinoma according to histologic activity of hepatitis.  Cancer. 1999;  86 248-254
    CrossrefPubMedSearch in Google Scholar
  • 85 Khono H, Nagasue H, Hayashi H et al.. Postoperative adjuvant chemotherapy after radical hepatic resection for hepatocellular carcinoma (HCC).  Hepatogastroenterology. 1996;  43 1405-1409
    PubMedSearch in Google Scholar
  • 86 Lau W Y, Leung T W, Ho S K et al.. Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial.  Lancet. 1999;  353 797-801
    CrossrefPubMedSearch in Google Scholar
  • 87 Yamamoto M, Arii S, Sughara K et al.. Adjuvant oral chemotherapy after curative resection of hepatocellular carcinoma.  Br J Surg. 1996;  83 336-340
    CrossrefPubMedSearch in Google Scholar
  • 88 Ono T, Nagasue N, Kohno H et al.. Adjuvant chemotherapy with epirubicin and carmofur after radical resection of hepatocellular carcinoma: a prospective randomized study.  Semin Oncol. 1997;  24(suppl 6) S6-18
    PubMedSearch in Google Scholar
  • 89 Takayama T, Sekine T, Makuuchi M et al.. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial.  Lancet. 2000;  356 802-807
    CrossrefPubMedSearch in Google Scholar
  • 90 Ikeda K, Arase Y, Saitoh S et al.. Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor: a prospective randomized study of hepatitis C virus-related liver cancer.  Hepatology. 2000;  32 228-232
    CrossrefPubMedSearch in Google Scholar
  • 91 Kubo S, Nishiguchi S, Hirohashi K et al.. Effects of long-term postoperative interferon-alpha therapy on intrahepatic recurrence after resection of hepatitis C virus-related hepatocellular carcinoma.  Ann Intern Med. 2001;  134 963-967
    PubMedSearch in Google Scholar
  • 92 Shiratobi Y, Shiina S, Teratani T et al.. Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus.  Ann Intern Med. 2003;  138 299-306
    CrossrefPubMedSearch in Google Scholar
  • 93 Lin S M, Lin C J, Hsu C W et al.. Prospective randomized controlled study of interferon-alpha in preventing hepatocellular carcinoma recurrence after medical ablation therapy for primary tumors.  Cancer. 2004;  100 376-382
    CrossrefPubMedSearch in Google Scholar
  • 94 Boucher E, Corbinais S, Rolland Y. Adjuvant intra-arterial injection of iodine-131-labeled lipiodol after resection of hepatocellular carcinoma.  Hepatology. 2003;  38 1237-1241
    CrossrefPubMedSearch in Google Scholar
  • 95 Majno P E, Sarasin F P, Mentha G. Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: an outcome-oriented decision analysis.  Hepatology. 2000;  31 899-906
    CrossrefPubMedSearch in Google Scholar
  • 96 Llovet J M, Bruix J, Gores G. Surgical resection vs transplantation for early hepatocellular carcinoma: clues for the best strategy.  Hepatology. 2000;  31 1019-1021
    CrossrefPubMedSearch in Google Scholar
  • 97 Belghiti J, Cortes A, Abdalla E et al.. Resection prior to liver transplantation for hepatocellular carcinoma.  Ann Surg. 2003;  238 885-893
    CrossrefPubMedSearch in Google Scholar
  • 98 Sala M, Fuster J, Llovet J M et al.. High pathological risk of recurrence after surgical resection for HCC. An indication for liver transplantation.  Liver Transpl. 2004;  10 1294-1300
    CrossrefPubMedSearch in Google Scholar
  • 99 Esquivel C O, Iwatsuki S, Gordon R D, Starzl T E. Transplantation for primary liver cancer. In: Wanebo HJ Hepatic and Biliary Cancer. New York; Marcel Dekker 1987: 484
    Search in Google Scholar
  • 100 Lotze M T, Wanebo H J. Current and future research directions in management of hepatic cancer. In: Wanebo HJ Hepatic and Biliary Cancer. New York; Marcel Dekker 1987: 512
    Search in Google Scholar
  • 101 Ringe B, Pichlmayr R, Wittekind C, Tusch G. Surgical treatment of hepatocellular carcinoma: experience with liver resection and transplantation in 198 patients.  World J Surg. 1991;  15 270-285
    CrossrefPubMedSearch in Google Scholar
  • 102 Iwatsuki S, Starzl T E, Sheahan D G et al.. Hepatic resection versus transplantation for hepatocellular carcinoma.  Ann Surg. 1991;  214 221-228
    CrossrefPubMedSearch in Google Scholar
  • 103 Iwatsuki S, Gordon R D, Shaw Jr B W et al.. Role of liver transplantation in cancer therapy.  Ann Surg. 1985;  202 401-407
    CrossrefPubMedSearch in Google Scholar
  • 104 Bismuth H, Chiche L, Adam R, Castaing D, Diamond T, Dennison A. Liver resection versus transplantation for hepatocellular carcinoma in cirrhosis.  Ann Surg. 1993;  218 145-151
    CrossrefPubMedSearch in Google Scholar
  • 105 Bruix J, Llovet J M. Prognostic prediction and treatment strategy in hepatocellular carcinoma.  Hepatology. 2002;  35 519-524
    CrossrefPubMedSearch in Google Scholar
  • 106 Roayaie S, Ben-Haim M, Fishbein T M et al.. Comparison of surgical outcomes for hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: a Western experience.  Ann Surg Oncol. 2000;  7 764-770
    CrossrefPubMedSearch in Google Scholar
  • 107 Llovet J M, Sala M, Fuster J et al.. Predictors of drop-out and survival of patients with hepatocellular carcinoma candidates for liver transplantation.  Hepatology. 2003;  38 763A
    PubMedSearch in Google Scholar
  • 108 Yao F, Bass N, Nikolai B et al.. A follow-up analysis of the pattern and predictors of dropout from the waiting list for liver transplantation in patients with hepatocellular carcinoma: implications for the current organ allocation policy.  Liver Transpl. 2003;  9 684-692
    CrossrefPubMedSearch in Google Scholar
  • 109 Maddala Y K, Stadheim L, Andrews J C et al.. Drop-out rates of patients with hepatocellular cancer listed for liver transplantation: outcome with chemoembolization.  Liver Transpl. 2004;  10 449-455
    CrossrefPubMedSearch in Google Scholar
  • 110 Bruix J, Fuster J, Llovet J M. Liver transplantation for hepatocellular carcinoma: Foucault pendulum vs evidence-based decision.  Liver Transpl. 2003;  9 700-702
    CrossrefPubMedSearch in Google Scholar
  • 111 Marsh J W, Geller D, Finkelstein S et al.. Role of liver transplantation for hepatobiliary malignant disorders.  Lancet Oncol. 2004;  5 480-488
    CrossrefPubMedSearch in Google Scholar
  • 112 Schwartz M. Liver transplantation for hepatocellular carcinoma.  Gastroenterology. 2004;  127 S268-S276
    PubMedSearch in Google Scholar
  • 113 Stone M J, Klintmalm G B, Polter D et al.. Neoadjuvant chemotherapy and liver transplantation for hepatocellular carcinoma: a pilot study in 20 patients.  Gastroenterology. 1993;  104 196-202
    PubMedSearch in Google Scholar
  • 114 Olthoff K M, Rosove M H, Shackleton C R et al.. Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma.  Ann Surg. 1995;  221 734-741
    PubMedSearch in Google Scholar
  • 115 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;  226 688-701
    CrossrefPubMedSearch in Google Scholar
  • 116 Oldhafer K J, Chavan A, Fruhauf N R et al.. Arterial chemoembolization before liver transplantation in patients with hepatocellular carcinoma: marked tumor necrosis, but no survival benefit?.  J Hepatol. 1998;  29 953-959
    CrossrefPubMedSearch in Google Scholar
  • 117 Graziadei I W, 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;  9 557-563
    CrossrefPubMedSearch in Google Scholar
  • 118 Mazzaferro V, Battiston C, Perrone S. Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study.  Ann Surg. 2004;  240 900-909
    CrossrefPubMedSearch in Google Scholar
  • 119 Lu D S, Yu N C, Raman S S et al.. Radiofrequency ablation of hepatocellular carcinoma: treatment success as defined by histologic examination of the explanted liver.  Radiology. 2005;  234 954-960
    CrossrefPubMedSearch in Google Scholar
  • 120 Llovet J M, Mas X, Aponte J et al.. Cost-effectiveness of adjuvant therapy for hepatocellular carcinoma before liver transplantation.  Gut. 2002;  50 123-128
    CrossrefPubMedSearch in Google Scholar
  • 121 Roayaie S, Llovet J M. Extended indications for liver transplantation in hepatocellular carcinoma.  Clin Liver Dis. 2005;  9 315-328
    CrossrefPubMedSearch in Google Scholar
  • 122 Miller C M, Gondolesi G E, Florman S et al.. One hundred nine living donor liver transplants in adults and children: a single-center experience.  Ann Surg. 2001;  234 301-312
    CrossrefPubMedSearch in Google Scholar
  • 123 Marcos A. Right lobe living donor liver transplantation: a review.  Liver Transpl. 2000;  6 3-20
    PubMedSearch in Google Scholar
  • 124 Trotter J, Wachs M, Everson G, Kam I. Adult-to-adult transplantation of the right hepatic lobe from living donor.  N Engl J Med. 2002;  346 1074-1082
    CrossrefPubMedSearch in Google Scholar
  • 125 Sugawara Y, Makuuchi M, Takayama T. Safe donor hepatectomy for living related liver transplantation.  Liver Transpl. 2002;  8 58-62
    CrossrefPubMedSearch in Google Scholar
  • 126 Ben-Haim M, Emre S, Fishbein T M et al.. Critical graft size in adult-to-adult living donor liver transplantation: impact of the recipient's disease.  Liver Transpl. 2001;  7 948-953
    CrossrefPubMedSearch in Google Scholar
  • 127 Sarasin F, Majno P, Llovet J M, Mentha J, Bruix J, Hadengue A. Liver donor liver transplantation for early hepatocellular carcinoma: a cost-effectiveness perspective.  Hepatology. 2001;  33 1073-1079
    CrossrefPubMedSearch in Google Scholar
  • 128 Garcia-Retortillo M, Forns X, Llovet J M et al.. Hepatitis C recurrence is more severe after living donor transplantation compared to cadaveric liver transplantation.  Hepatology. 2004;  40 699-707
    CrossrefPubMedSearch in Google Scholar
  • 129 Bozorgzadeh A, Jain A, Ryan C et al.. Impact of hepatitis C viral infection in primary cadaveric liver allograft versus primary living-donor allograft in 100 consecutive liver transplant recipients receiving tacrolimus.  Transplantation. 2004;  77 1066-1107
    PubMedSearch in Google Scholar
  • 130 Gaglio  P J, Malireddy S, Levitt B S. Increased risk of cholestatic hepatitis C in recipients of grafts from living versus cadaveric liver donors.  Liver Transpl. 2003;  9 1028-1035
    CrossrefPubMedSearch in Google Scholar
  • 131 Forns Garcia-Retortillo M, Forns X. Prevention and treatment of hepatitis C virus recurrence after liver transplantation.  J Hepatol. 2004;  41 2-10
    CrossrefPubMedSearch in Google Scholar
  • 132 Starzl T E, Marchioro T L, Faris T D. Liver transplantation.  Ann Intern Med. 1966;  64 473-477
    PubMedSearch in Google Scholar

Josep M LlovetM.D. 

Division of Liver Diseases, RM Transplantation Institute, Mount Sinai School of Medicine

1425 Madison Ave, 11F-70, Box:1104

New York, NY10029

Email: Josep.Llovet@mssm.edu