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Downstaging Advanced Hepatocellular Carcinoma to the Milan Criteria May Provide a Comparable Outcome to Conventional Milan Criteria

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background and Aims

Many hepatocellular carcinoma (HCC) patients met the appropriate criteria and accepted liver transplantation after successful downstaging therapies; however, the outcome in these patients is unclear. We aim to compare the outcome of patients meeting the Milan criteria at the beginning and after successful downstaging therapies.

Patients and Methods

Between July 2001 and January 2013, 112 patients were diagnosed with early-stage HCC that met the Milan criteria. Of these patients, 58 patients did not meet the Milan criteria initially but did after successful downstaging therapies. We retrospectively collected and then compared the baseline characteristics, postoperative complications, survival rate, and tumor recurrence rate of these two groups. Kaplan–Meier analyses were used to estimate the long-term overall survival and tumor-free survival in these patients.

Results

No significant differences were observed between the two groups with respect to baseline donor and recipient characteristics. The downstaging Milan group showed similar tumor characteristics compared to the conventional Milan group, except the downstaging group had better tumor histopathologic grading (P = 0.027). The 1-, 3-, and 5-year overall survival rates were comparable at 91.4, 82.8, and 70.7 %, respectively, in the downstaging Milan criteria and 92.0, 85.7, and 74.1 %, respectively, according to the initial Milan criteria (P = 0.540). The 1-, 3-, and 5-year tumor-free survival rates between the two groups were not statistically significant (P = 0.667).

Conclusion

Successful downstaging therapies can provide a comparable posttransplantation overall survival and tumor-free survival rates after liver transplantation.

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Abbreviations

LT:

Liver transplantation

LDLT:

Living donor liver transplantation

DDLT:

Deceased donor liver transplantation

HCC:

Hepatocellular carcinoma

TACE:

Transarterial chemoembolization

RAF:

Radiofrequency ablation

EI:

Alcohol injection

TACI:

Transarterial chemoinfusion

AFP:

Alpha fetoprotein

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

MELD:

Model for end stage liver disease

mRECIST:

Modified version of the Response Evaluation Criteria in Solid Tumors

BMI:

Body mass index

HBcAb:

Hepatitis B core antibody

References

  1. El-Serag HB. Hepatocellular carcinoma: an epidemiologic view. J Clin Gastroenterol 2002;35:S72-S78

    Article  PubMed  Google Scholar 

  2. Rossi L, Zoratto F, Papa A, Iodice F, et al. Current approach in the treatment of hepatocellular carcinoma. World J Gastrointest Oncol 2010;2:348-359

    Article  PubMed  Google Scholar 

  3. Gordon-Weeks AN, Snaith A, Petrinic T, et al. Systematic review of outcome of downstaging hepatocellular cancer before liver transplantation in patients outside the Milan criteria. Br J Surg. 2011 Sep;98(9):1201-8

  4. Parkin M, Bray F, Ferlay J, et al. Global cancer statistics. 2002. CA Cancer J Clin. 2005;55:74-108

    Article  PubMed  Google Scholar 

  5. Lei JY, Yan LN. Outcome comparisons among the Hangzhou, Chengdu and UCSF criteria for hepatocellular carcinoma liver transplantation after successful down-staging therapies. J Gastrointest Surg 2013 Jan 17. [Epub ahead of print]

  6. Belghiti J, Carr BI, Greig PD, et al. Treatment before liver transplantation for HCC. Ann Surg Oncol. 2008 Apr;15(4):993-1000

  7. Penn I. Hepatic transplantation for primary and metastatic cancers of the liver. Surgery 1991;110:726-734

    PubMed  CAS  Google Scholar 

  8. Pichlmayr R, Weimann A, Ringe B. Indication for liver transplantation in hepatobiliary malignancy. Hepatology 1994;20:338-408

    Google Scholar 

  9. Ringe B, Pichlmayr R, Wittekind C, et al. Surgical treatment of hepatocellular carcinoma: experience with liver resection and transplantation in 198 patients. World J Surg. 1991;15:270

    Article  PubMed  CAS  Google Scholar 

  10. Bismuth H, Chiche L, Adam R, et al. Hepatic resection versus transplantation for hepatocellular carcinoma. Ann Surg 1991;214:221

    Article  Google Scholar 

  11. 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

    Google Scholar 

  12. Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellur carcinoma: expansion of the tumor size limites does not adversely impact survival. Hepatology. 2001;6:1394-1403

    Google Scholar 

  13. Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, Liang TB, Wu LM. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation 2008;85: 1726-1732

    Article  PubMed  CAS  Google Scholar 

  14. Lei JY, Yan LN. Comparison between living donor liver transplantation recipients who met the Milan and UCSF criteria after successful downstaging therapies. J Gastrointest Surg.2012 Nov; 16(11):2120-5

  15. Klintmalm GB, liver transplantation for hepatocellular carcinoma: a registry report of the impact of tumor characteristics on outcome. Ann Surg 1998;228:479-490

    Article  PubMed  CAS  Google Scholar 

  16. Yokoyama I, Todo S, Iwatsuki S, Starzl TE. Liver transplantation in the treatment of primary liver cancer. Hepatogastroenterology 1990;37:188-193

    PubMed  CAS  Google Scholar 

  17. Yao FY, Kerlan RK Jr, Hirose R, et al. excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology. 2008; 48(3):819-27

    Article  PubMed  Google Scholar 

  18. Chapman WC, Majella Doyle MB, Stuart JE, et al. Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation. Ann Surg 2008;248:617-625

    PubMed  Google Scholar 

  19. De Luna W, Sze D, Ahened A, Ha BY, et al. Transarterial chemoinfusion for hepatocellular carcinoma as downstaging therapy and a bridge toward liver transplantation. Am J Transplant 2009;9:1158-1168

    Article  PubMed  Google Scholar 

  20. Cillo U, Vitale A, Grigoletto F, et al. Intention-to-treat analysis of liver transplantation in selected, aggressively treated HCC patients exceeding the Milan criteria. Am J Transplant 2007;7:972-981

    Article  PubMed  CAS  Google Scholar 

  21. Otto G, Herber S, Heise M, et al. Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma. Liver Transpl 2006;12:1260-1267

    Article  PubMed  Google Scholar 

  22. Graziadei IW, 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

    Article  PubMed  Google Scholar 

  23. Yao FY. Expanding criteria for hepatocellular carcinoma: down-staging with a view to liver transplantation- yes. Smmin Liver Diseas 2006;26:239-247

    Article  Google Scholar 

  24. Bruix J, Sherman M, Liovet J, et al. Clinical management of hepatocellular carcinoma. Conclusion do the Barcellona-2000 EASL conference. J Hepatol 2001;35:4210-4230

    Google Scholar 

  25. Bruix J, Sherman M. Practice Guidelines Committee, American association for the study of liver diseases. Management of hepatocellular carcinoma. Hepatology 2005;42:1208-1236

    Article  PubMed  Google Scholar 

  26. Marsh JW, Dvorchik I, Iwatsuki S. UNOS policy in upgrading patients with HCC awaiting liver transplantation: too little too late. Transplantation 2000;69(Supple):S139

    Article  Google Scholar 

  27. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52-60

    Article  PubMed  CAS  Google Scholar 

  28. Edeline J, Boucher E, Rolland Y et al. Comparison of tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST in patients treated with sorafenib for hepatocellular carcinoma. Cancer. 2012;118:147-156

    Article  PubMed  CAS  Google Scholar 

  29. Yao FY, Xiao L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: validation of the UCSF expanded criteria based on pre-operative imaging. Am J Transpl 2007;7:2587-2596

    Article  CAS  Google Scholar 

  30. Ravaioli M, Grazi GL, Piscaglia F, et al. Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant 2008, 8(12):2547-57

    Article  PubMed  CAS  Google Scholar 

  31. Millonig G, Graziadei IW, Freund MC, et al. Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma. Liver Transpl 2007;13:272-279

    Article  PubMed  Google Scholar 

  32. Barakat O, Wood RP, Ozaki CF, et al. Morphological features of advanced hepatocellular carcinoma as a predictor of down-staging and liver transplantation: and intention-to-treat analysis. Liver Transpl 2010;16:289-299

    PubMed  Google Scholar 

  33. Yao FY, Breitenstein S, Broelsch CE, et al. Does a patient qualify for liver transplantation after the down-staging of hepatocellular carcinoma? Liver Transpl. 2011;17 Suppl 2:S109-16

    Article  PubMed  Google Scholar 

  34. Majno PE, Adam R, Bismuth H, et al. influence of preoperative transarterial lipodol chemombolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg 1997;226:688-701

    Article  PubMed  CAS  Google Scholar 

  35. Shi XJ, Jin X, Wang MQ, et al. Outcomes of loco-regional therapy for down-staging of hepatocellular carcinoma prior to liver transplantation. Hepatobiliary Pancreat Dis Int. 2011;10(2):143-50

    Article  PubMed  Google Scholar 

  36. Liovet JM, Schwartz M, Fuster J, Bruix J. Expand criteria for hepatocellular carcinoma through down-staging prior to liver transplantation: not yet there. Semin Liver Dis. 2006 Aug;26(3):248-53

  37. Nissen NN, Menon V, Bresee C, et al. Recurrent hepatocellular carcinoma after liver transplant: identifying the high-risk patient. HPB(Oxford).2011;13(9):626-32

    Google Scholar 

  38. Bertuzzo VR, Cescon M, Ravaioli M, et al. Analysis of factors affecting recurrence of hepatocellular carcinoma after liver transplantation with a special focus on inflammation markers. Transplantation. 2011;91(11):1279-85

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by grants from The National Sciences and Technology Major Project of China (2012ZX10002-016 and 2012ZX10002-017). And We thank the China Liver Transplant Registry System for providing all of the data.

Conflict of Interest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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Author notes

  1. Jianyong Lei

    Present address: Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, 610041, China

Authors and Affiliations

  1. Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, 610041, China

    Wentao Wang & Lunan Yan

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  1. Jianyong Lei
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  2. Wentao Wang
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Correspondence to Wentao Wang.

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Lei, J., Wang, W. & Yan, L. Downstaging Advanced Hepatocellular Carcinoma to the Milan Criteria May Provide a Comparable Outcome to Conventional Milan Criteria. J Gastrointest Surg 17, 1440–1446 (2013). https://doi.org/10.1007/s11605-013-2229-y

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  • DOI: https://doi.org/10.1007/s11605-013-2229-y

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