Skip to main content
SpringerLink
Log in

Downstaging Hepatocellular Carcinoma for Liver Transplantation

  • Reference work entry
  • First Online:
Contemporary Liver Transplantation

Part of the book series: Organ and Tissue Transplantation ((OTT))

  • 1471 Accesses

Abstract

The incidence of hepatocellular carcinoma (HCC) has been on the rise in the United States in the past few decades. Liver transplantation is considered the treatment of choice for patients who present with stage II HCC and fall within the MILAN criteria with a 5-year overall survival of 65–70 %. Unfortunately, most of the patients present with advanced disease and only 10–20 % are eligible for orthotopic liver transplant (OLT). In an attempt to help patients meet the criteria for OLT, several modalities are being used to decrease tumor load and downstage patients, namely, radiofrequency ablation (RFA) and transarterial chemoembolization (TACE). The main problems with the concept of downstaging reside in identifying patients who should undergo downstaging, defining the end points of successful downstaging and deciding on a reasonable time frame before listing for transplant. Several reports have been published that show good results with downstaging. The percentage of patients who were successfully downstaged in published series ranged from 24 % to 70 %. Overall survival after downstaging and OLT was approximately 65 % at 5 years in most of the series. This supports the idea that downstaging is a reasonable method for treatment of patients who present with unresectable HCC that do not fit the criteria for initial liver transplantation. It is also useful in selecting patients with favorable biology that would otherwise not receive OLT. There is currently no evidence in the literature to suggest that patients who are downstaged and receive OLT do worse than patients that present within MILAN transplant criteria, a notion that should drive surgeons and hepatologists to aggressively treat stage III HCC patients with the goal of downstaging.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Adam R, Azoulay D (2005) Is primary resection and salvage transplantation for hepatocellular carcinoma a reasonable strategy? Ann Surg 241(4):671–672

    Article  PubMed  PubMed Central  Google Scholar 

  • Adam R, Azoulay D, Castaing D, Eshkenazy R, Pascal G, Hashizume K et al (2003) Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy? Ann Surg 238(4):508–518, discussion 518–519

    PubMed  PubMed Central  Google Scholar 

  • Altekruse SF, Henley SJ, Cucinelli JE, McGlynn KA (2014) Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol 109(4):542–553

    Article  PubMed  PubMed Central  Google Scholar 

  • Barakat O, Wood RP, Ozaki CF, Ankoma-Sey V, Galati J, Skolkin M et al (2010) Morphological features of advanced hepatocellular carcinoma as a predictor of downstaging and liver transplantation: an intention-to-treat analysis. Liver Transpl 16(3):289–299

    PubMed  Google Scholar 

  • Belghiti J, Cortes A, Abdalla EK, Régimbeau JM, Prakash K, Durand F et al (2003) Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg 885–92:892–893

    Google Scholar 

  • Bova V, Miraglia R, Maruzzelli L, Vizzini GB, Luca A (2013) Predictive factors of downstaging of hepatocellular carcinoma beyond the Milan criteria treated with intra-arterial therapies. Cardiovasc Intervent Radiol 36(2):433–439

    Article  PubMed  Google Scholar 

  • Buscarini L, Buscarini E, Di Stasi M, Vallisa D, Quaretti P, Rocca A (2001) Percutaneous radiofrequency ablation of small hepatocellular carcinoma: long-term results. Eur Radiol 11(6):914–921

    Article  CAS  PubMed  Google Scholar 

  • Chapman WC, Majella Doyle MB, Stuart JE, Vachharajani N, Crippin JA, Anderson CD et al (2008) Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation. Ann Surg 248(4):617–625

    PubMed  Google Scholar 

  • Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A, OLT for HCC Consensus Group (2012) Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 13(1):e11–e22

    Article  PubMed  Google Scholar 

  • DeLuna W, Sze DY, Ahmed A, Ha BY, Ayoub W, Keefee EB et al (2009) Transarterial chemoinfusion for hepatocellular carcinoma as downstaging therapy and a bridge toward liver transplantation. Am J Transplant 9(5):1158–1168

    Article  CAS  Google Scholar 

  • Gamblin TC, Geller DA (2005) Downstaging hepatocellular carcinoma prior to liver transplantation. Liver Transpl 11(12):1466–1468

    Article  PubMed  Google Scholar 

  • Gordon-Weeks AN, Snaith A, Petrinic T, Friend PJ, Burls A, Silva MA (2011) Systematic review of outcome of downstaging hepatocellular cancer before liver transplantation in patients outside the Milan criteria. Br J Surg 98(9):1201–1208

    Article  CAS  PubMed  Google Scholar 

  • Graziadei IW, Sandmueller H, Waldenberger P, Koenigsranier A, Nachbaur K, Jaschke W et al (2003) Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome. Liver Transpl 9(6):557–563

    Article  PubMed  Google Scholar 

  • Jang JW, You CR, Kim CW, Bae SH, Yoon SK, Yoo YK et al (2010) Benefit of downsizing hepatocellular carcinoma in a liver transplant population. Aliment Pharmacol Ther 31(3):415–423

    Article  CAS  PubMed  Google Scholar 

  • Lei J, Wang W, Yan L (2013a) Downstaging advanced hepatocellular carcinoma to the Milan criteria may provide a comparable outcome to conventional Milan criteria. J Gastrointest Surg 17(8):1440–1446

    Article  PubMed  Google Scholar 

  • Lei JY, Yan LN, Wang WT (2013b) Transplantation vs resection for hepatocellular carcinoma with compensated liver function after downstaging therapy. World J Gastroenterol 19(27):4400–4408

    Article  PubMed  PubMed Central  Google Scholar 

  • Lewandowski RJ, Kulik LM, Riaz A, Senthilnathan S, Mulcahy MF, Ryu RK et al (2009) A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant 9(8):1920–1928

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Fuster J, Bruix J (1999) Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30(6):1434–1440

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J (2008) SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378–390

    Article  CAS  PubMed  Google Scholar 

  • Majno PE, Sarasin FP, Mentha G, Hadenque A (2000) 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 31(4):899–906

    Article  CAS  PubMed  Google Scholar 

  • Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F et al (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334(11):693–699

    Article  CAS  PubMed  Google Scholar 

  • Otto G, Herber S, Heise M, Lohse AW, Mönch C, Bittinger F et al (2006) Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma. Liver Transpl 12(8):1260–1267

    Article  PubMed  Google Scholar 

  • Pomfret EA, Washburn K, Wald C, Nalesnik MA, Douglas D, Russo M et al (2010) Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States. Liver Transpl 16(3):262–278

    Article  PubMed  Google Scholar 

  • Poon RT, Fan ST, Lo CM, Liu CL, Wong J (2002) 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 235(3):373–382

    Article  PubMed  PubMed Central  Google Scholar 

  • Ravaioli M, Grazi GL, Piscaglia F, Trevisani F, Cescon M, Ercolani G et al (2008) Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant 8(12):2547–2557

    Article  CAS  PubMed  Google Scholar 

  • Rossi S, Di Stasi M, Buscarini E, Quaretti P, Garbagnati F, Squassante L et al (1996) Percutaneous RF interstitial thermal ablation in the treatment of hepatic cancer. AJR Am J Roentgenol 167(3):759–768

    Article  CAS  PubMed  Google Scholar 

  • Sala M, Verala M, Bruix J (2004) Selection of candidates with HCC for transplantation in the MELD era. Liver Transpl 10(2):S4–S9

    Article  PubMed  Google Scholar 

  • Salem R, Thurston KG, Carr BI, Goin JE, Geschwind JF (2002) Yttrium-90 microspheres: radiation therapy for unresectable liver cancer. J Vasc Interv Radiol 13:S223–S229

    Article  PubMed  Google Scholar 

  • Sharr WW, Chan SC, Lo CM (2014) Current status of downstaging of hepatocellular carcinoma before liver transplantation. Transplantation 97(8):S10–S17

    Article  PubMed  Google Scholar 

  • Signoriello S, Annunziata A, Lama N, Signoriello G, Chiodini P, De Sio I et al (2012) Survival after locoregional treatments for hepatocellular carcinoma: a cohort study in real-world patients. Sci World J 2012:1–8

    Article  Google Scholar 

  • Toso C, Kneteman NM, James Shapiro AM, Bigam DL (2009) The estimated number of patients with hepatocellular carcinoma selected for liver transplantation using expanded selection criteria. Transpl Int 22(9):869–875

    Article  PubMed  Google Scholar 

  • Toso C, Mentha G, Kneteman NM, Majno P (2010) The place of downstaging for hepatocellular carcinoma. J Hepatol 52(6):930–936

    Article  PubMed  Google Scholar 

  • Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A et al (2001) Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33(6):1394–13403

    Article  CAS  PubMed  Google Scholar 

  • Yao FY, Kerlan RK Jr, Hirose R, Davern TJ 3rd, Bass NM, Feng S et al (2008) Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology 48(3):819–827

    Article  PubMed  PubMed Central  Google Scholar 

  • Yeung YP, Lo CM, Liu CL, Wong BC, Fan ST, Wong J (2005) Natural history of untreated nonsurgical hepatocellular carcinoma. Am J Gastroenterol 100(9):1995–2004

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, University of Pittsburgh, 3459 Fifth Avenue, UPMC Montefiore, 7 South, Pittsburgh, PA, 15213-2582, USA

    Mohammad Khreiss & David A. Geller

Authors
  1. Mohammad Khreiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David A. Geller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David A. Geller .

Editor information

Editors and Affiliations

  1. Nicoletti Family Professor of Transplant Surgery, Director, Jefferson Transplant Institute, Director, Division of Transplantation, Surgical Director, Kimmel Cancer Center – Jefferson Liver Tumor Center, Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA

    Cataldo Doria

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this entry

Cite this entry

Khreiss, M., Geller, D.A. (2017). Downstaging Hepatocellular Carcinoma for Liver Transplantation. In: Doria, C. (eds) Contemporary Liver Transplantation. Organ and Tissue Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-07209-8_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-07209-8_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-07208-1

  • Online ISBN: 978-3-319-07209-8

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation