Semin Liver Dis 2006; 26(3): 239-247
DOI: 10.1055/s-2006-947295
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Expanded Criteria for Hepatocellular Carcinoma: Down-Staging with a View to Liver Transplantation-Yes

Francis Y. Yao1
  • 1Professor of Clinical Medicine and Surgery, University of California, San Francisco
Further Information

Publication History

Publication Date:
19 July 2006 (online)

ABSTRACT

In patients with hepatocellular carcinoma (HCC) exceeding conventional Milan criteria (one lesion ≤ 5 cm or two or three lesions ≤ 3 cm) for orthotopic liver transplantation (OLT), down-staging of the tumor before OLT presents an unique and intriguing perspective on tumor biology and expanded criteria for OLT. According to the University of California, San Francisco protocol, the eligibility criteria for down-staging included one lesion ≤ 8 cm, two or three lesions each ≤ 5 cm with total tumor diameter ≤ 8 cm, or four or five lesions each ≤ 3 cm with total tumor diameter ≤ 8 cm. In the majority of these patients, successful down-staging using well-defined endpoints could be achieved prior to OLT, without resulting in post-transplantation HCC recurrence. The promise of down-staging warrants consideration of a unified policy granting patients with HCC that has been successfully down-staged the same priority listing for OLT as those meeting conventional criteria.

REFERENCES

  • 1 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
  • 2 Befeler A S, Hayashi P H, Di Bisceglie A M. Liver transplantation for hepatocellular carcinoma.  Gastroenterology. 2005;  128 1752-1764
  • 3 United Network for Organ Sharing, Policy 3.6 .Available at: http://www.unos.org/policiesandbylaws/policies.asp?resources= true Accessed February 6, 2006
  • 4 Wiesner R H, Freeman R B, Mulligan D C. Liver transplantation for hepatocellular cancer: the impact of the MELD allocation policy.  Gastroenterology. 2004;  127(suppl 1) S261-S267
  • 5 Broelsch C E, Frilling A, Malago M. Should we expand the criteria for liver transplantation for hepatocellular carcinoma-yes, of course!.  J Hepatol. 2005;  43 569-573
  • 6 Hiatt J R, Carmody I C, Busuttil R W. Should we expand the criteria for hepatocellular carcinoma with living-donor liver transplantation?-no, never.  J Hepatol. 2005;  43 573-577
  • 7 Bruix J, Fuster J, Llovet J. Liver transplantation for hepatocellular carcinoma: Foucault pendulum versus evidence-based decision.  Liver Transpl. 2003;  9 700-702
  • 8 Roayaie S, Llovet J M. Liver transplantation for hepatocellular carcinoma: is expansion of criteria justified?.  Clin Liver Dis. 2005;  9 315-328
  • 9 Eng S C, Kowdley K V. Expansion of criteria for liver transplantation in HCC: a slippery slope?.  Gastroenterology. 2002;  122 579-582
  • 10 El-Serag H B. Hepatocellular carcinoma: recent trends in the United States.  Gastroenterology. 2004;  127(suppl 1) S27-S34
  • 11 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
  • 12 Yao F Y, Ferrell L, Bass N M et al.. Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria.  Liver Transpl. 2002;  8 765-774
  • 13 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
  • 14 Marsh J W, Dvorchik I. Liver organ allocation for hepatocellular carcinoma: are we sure?.  Liver Transpl. 2003;  9 693-696
  • 15 Leung J Y, Zhu A X, Gordon F D et al.. Liver transplantation for early-stage hepatocellular carcinoma: results of a multicenter study.  Liver Transpl. 2004;  10 1343-1354
  • 16 Decaens T, Roudot-Thoraval F, Hadni-Bresson S et al.. What is the impact of UCSF expansion criteria according to pre-liver transplantation tumor characteristics on survival: results from 14 French centers [abstract].  Hepatology. 2004;  40(suppl 1) 550A
  • 17 Schwartz M. Liver transplantation for hepatocellular carcinoma.  Gastroenterology. 2004;  127(suppl 1) S268-S276
  • 18 Hwang S, Lee S G, Joh J W et al.. Liver transplantation for adult patients with hepatocellular carcinoma in Korea: comparison between cadaveric donor and living donor liver transplantation.  Liver Transpl. 2005;  11 1265-1272
  • 19 Shetty K, Timmins K, Brensinger C et al.. Liver transplantation for hepatocellular carcinoma: validation of the present selection criteria in predicting outcome.  Liver Transpl. 2004;  10 911-918
  • 20 Yao F Y, Roberts J P. Applying expanded criteria to liver transplantation for hepatocellular carcinoma: too much too soon, or is now the time?.  Liver Transpl. 2004;  10 919-921
  • 21 Yao F Y, Bass N M, Ascher N L, Roberts J P. Liver transplantation for hepatocellular carcinoma: a 4-year prospective study validating expanded criteria based on pre-operative staging [abstract].  Hepatology. 2005;  42(suppl 1) 197A
  • 22 Sala M, Varela M, Bruix J. Selection of candidates with HCC for transplantation in the MELD era.  Liver Transpl. 2004;  10 S4-S9
  • 23 Jonas S, Bechstein W O, Steinmuller T et al.. Vascular invasion and histologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis.  Hepatology. 2001;  33 1080-1086
  • 24 Hemming A W, Cattral M S, Reed A I et al.. Liver transplantation for hepatocellular carcinoma.  Ann Surg. 2001;  233 652-659
  • 25 De Carlis L, Glacomoni A, Laanterio A et al.. Liver transplantation for hepatocellular cancer: should the current indication criteria be changed?.  Transpl Int. 2003;  16 115-122
  • 26 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
  • 27 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
  • 28 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
  • 29 Llovet J M, Mas X, Aponte J J et al.. Cost-effectiveness of adjuvant therapy for hepatocellular carcinoma before liver transplantation.  Gut. 2002;  50 123-128
  • 30 Mazzaferro V, Battiston C, Perrone S et al.. Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study.  Ann Surg. 2004;  240 900-909
  • 31 Yao F Y, Kinkhabwala M, LaBerge J M et al.. The impact of pre-operative loco-regional treatments on survival following liver transplantation for hepatocellular carcinoma.  Am J Transplant. 2005;  5 795-804
  • 32 Lu D S, Yu N C, Raman S S et al.. Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation.  Hepatology. 2005;  41 1130-1137
  • 33 Yao F Y, Ferrell L D, Bass N M et al.. Liver transplantation for hepatocellular carcinoma: the impact of the degree of tumor necrosis from pre-operative loco-regional therapy on recurrence [abstract].  Gastroenterology. 2005;  128(suppl 2) A689
  • 34 Sharma P, Balan V, Hernandez J L et al.. Liver transplantation for hepatocellular carcinoma: the MELD impact.  Liver Transpl. 2004;  10 36-41
  • 35 Yao F Y, Bass N M, Ascher N L, Roberts J P. Liver transplantation for hepatocellular carcinoma: lessons from the first year under the model of end-stage liver disease (MELD) organ allocation policy.  Liver Transpl. 2004;  10 621-630
  • 36 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
  • 37 Roayaie S, Frischer J S, Emre S H et al.. Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinoma larger than 5 centimeters.  Ann Surg. 2002;  235 533-539
  • 38 Yao F Y, Hirose R, LaBerge J et al.. A prospective study on down-staging of hepatocellular carcinoma prior to liver transplantation.  Liver Transpl. 2005;  11 1505-1514
  • 39 Marsh J W, Dvorchik I, Iwatsuki S. UNOS policy in upgrading patients with HCC awaiting liver transplantation: too little too late [abstract].  Transplantation. 2000;  69(suppl) S139
  • 40 Bruix J, Llovet J M. Prognostic prediction and treatment strategy in hepatocellular carcinoma.  Hepatology. 2002;  35 519-524
  • 41 Pugh R N, Murray-Lyon I M, Dawson J L et al.. Transection of the oesophagus for bleeding oesophageal varices.  Br J Surg. 1973;  60 646-649
  • 42 Lin S M, Lin C J, Lin C C et al.. Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma < or = 4 cm.  Gastroenterology. 2004;  127 1714-1723
  • 43 Sala M, Llovet J M, Vilana R for the Barcelona Clinic Liver Cancer Group et al. Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma.  Hepatology. 2004;  40 1352-1360
  • 44 Omata M, Tateishi R, Yoshida H, Shiina S. Treatment of hepatocellular carcinoma by percutaneous tumor ablation methods: ethanol injection therapy and radiofrequency ablation.  Gastroenterology. 2004;  127(suppl 1) S159-S166
  • 45 Marsh J W, Finkelstein S D, Demetris A J et al.. Genotyping of hepatocellular carcinoma in liver transplant recipients adds predictive power for determining recurrence-free survival.  Liver Transpl. 2003;  9 664-671

Francis Y YaoM.D. 

Professor of Clinical Medicine and Surgery, University of California, San Francisco

513 Parnassus Avenue, Room S-357, San Francisco, CA 94143-0538

    >