Advertisement

Predicting Hepatocellular Carcinoma Recurrence Beyond Milan Criteria After Liver Resection for Solitary Hepatocellular Carcinoma

  • Jong Man Kim
  • Jae-Won JohEmail author
  • Nam-Joon Yi
  • Gyu-Seong Choi
  • Kyunga Kim
  • Kwang-Woong Lee
  • Kyung-Suk Suh
Original Article
  • 115 Downloads

Abstract

Background and Purpose

Several hepatectomy patients with HCC who are initially transplantable (within MC) developed untransplantable HCC recurrence (beyond MC) after primary curative liver resection. The purpose of our study is to identify the risk factors of untransplantable hepatocellular carcinoma (HCC) recurrence after primary curative resection of solitary HCC and solitary HCC within Milan criteria (MC).

Methods

We retrospectively reviewed 592 patients with recurrent HCC who underwent liver resection due to solitary HCC between 2005 and 2011.

Results

All patients were Child-Pugh class A. At primary curative hepatectomy, 411 patients (69.4%) were diagnosed with HCC within MC and 181 patients (30.6%) had HCC beyond MC. The mean time from primary hepatectomy to recurrence was 14 months (range, 1–116 months). At HCC recurrence, 93 patients (15.7%) were diagnosed beyond MC. Multivariate analysis showed that microvascular invasion and a tumor grade of 3 or 4 were closely associated with a high risk of HCC recurrence beyond MC in patients who had hepatectomy for solitary HCC. Of the 411 patients within MC at primary curative hepatectomy, 54 patients (13.9%) developed HCC recurrence beyond MC. Multivariate analysis also showed that microvascular invasion and a tumor grade of 3 or 4 were closely associated with HCC recurrence beyond MC in these patients.

Conclusions

The present study suggests that the presence of certain unfavorable histological factors in patients who underwent initial liver resection of transplantable HCC within MC with good liver function predicted the development of recurrent HCC beyond MC.

Keywords

Hepatocellular carcinoma Milan criteria Hepatectomy Tumor recurrence Liver transplantation 

Abbreviations

MC

Milan criteria

HBV

Hepatitis B virus

HCV

Hepatitis C virus

NBNC

Non-B non-C

AST

Aspartate transaminase

ALT

Alanine transaminase

AFP

Alpha-fetoprotein

PIVKA-II

Protein induced by vitamin K absence or antagonist-II

INR

International normalized ratio

ICG

Indocyanine green retention test at 15 min

HCC

Hepatocellular carcinoma

TACE

Transarterial chemoembolization

RFA

Radiofrequency ablation

PEI

Percutaneous ethanol injection

LT

Liver transplantation

LR

Liver resection

PVTT

Portal vein tumor thrombosis

PET

Positron emission tomography

MRI

Magnetic resonance imaging

Notes

Author’s Contribution

Jong Man Kim: study design, literature search, data acquisition, analysis, interpretation and writing.

Jae-Won Joh and Nam Joon Yi: study design and data interpretation.

Kyunga Kim: Data analysis and interpretation.

Gyu-Seong Choi, Kwang-Woong Lee, and Kyung-Suk Suh: acquisition of data and analysis of data.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Yu SJ. A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world: 2010-2016. Clin Mol Hepatol. 2016;22:7–17.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Lee JM, Park JW, Choi BI. 2014 KLCSG-NCC Korea Practice Guidelines for the management of hepatocellular carcinoma: HCC diagnostic algorithm. Dig Dis. 2014;32:764–777.CrossRefPubMedGoogle Scholar
  3. 3.
    Bruix J, Sherman M, American Association for the Study of Liver D. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–1022.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    European Association For The Study Of The L, European Organisation For R, Treatment Of C. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–943.CrossRefGoogle Scholar
  5. 5.
    Cherqui D, Laurent A, Mocellin N, Tayar C, Luciani A, Van Nhieu JT, Decaens T, Hurtova M, Memeo R, Mallat A, Duvoux C. Liver resection for transplantable hepatocellular carcinoma: long-term survival and role of secondary liver transplantation. Ann Surg. 2009;250:738–746.CrossRefPubMedGoogle Scholar
  6. 6.
    Lee S, Hyuck David Kwon C, Man Kim J, Joh JW, Woon Paik S, Kim BW, Wang HJ, Lee KW, Suh KS, Lee SK. Time of hepatocellular carcinoma recurrence after liver resection and alpha-fetoprotein are important prognostic factors for salvage liver transplantation. Liver Transpl. 2014;20:1057–1063.CrossRefPubMedGoogle Scholar
  7. 7.
    Ferrer-Fabrega J, Forner A, Liccioni A, Miquel R, Molina V, Navasa M, Fondevila C, Garcia-Valdecasas JC, Bruix J, Fuster J. Prospective validation of ab initio liver transplantation in hepatocellular carcinoma upon detection of risk factors for recurrence after resection. Hepatology. 2016;63:839–849.CrossRefPubMedGoogle Scholar
  8. 8.
    Hwang S, Lee SG, Moon DB, Ahn CS, Kim KH, Lee YJ, Ha TY, Song GW. Salvage living donor liver transplantation after prior liver resection for hepatocellular carcinoma. Liver Transpl. 2007;13:741–746.CrossRefPubMedGoogle Scholar
  9. 9.
    Lee SG. Salvage living-donor liver transplantation to previously hepatectomized hepatocellular carcinoma patients: is it a reasonable strategy? Hepatobiliary Pancreat Dis Int. 2013;12:10–11.CrossRefPubMedGoogle Scholar
  10. 10.
    Zheng J, Chou JF, Gonen M, Vachharajani N, Chapman WC, Majella Doyle MB, Turcotte S, Vandenbroucke-Menu F, Lapointe R, Buettner S, Groot Koerkamp B, Ijzermans JNM, Chan CY, Goh BKP, Teo JY, Kam JH, Jeyaraj PR, Cheow PC, Chung AYF, Chow PKH, Ooi L, Balachandran VP, Kingham TP, Allen PJ, D'Angelica MI, DeMatteo RP, Jarnagin WR, Lee SY. Prediction of Hepatocellular Carcinoma Recurrence Beyond Milan Criteria After Resection: Validation of a Clinical Risk Score in an International Cohort. Ann Surg. 2017;266:693–701.CrossRefPubMedGoogle Scholar
  11. 11.
    Lee SY, Konstantinidis IT, Eaton AA, Gonen M, Kingham TP, D'Angelica MI, Allen PJ, Fong Y, DeMatteo RP, Jarnagin WR. Predicting recurrence patterns after resection of hepatocellular cancer. HPB (Oxford). 2014;16:943–953.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Han SR, Kim JM, Choi GS, Park JB, Kwon CH, Kim SJ, Joh JW. Protrusion of hepatocellular carcinoma is a predictor of early recurrence in hepatectomy patients after spontaneous rupture. Ann Surg Treat Res. 2016;91:17–22.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kim JM, Kwon CH, Joh JW, Park JB, Lee JH, Kim SJ, Paik SW, Park CK, Yoo BC. Outcomes after curative hepatectomy in patients with non-B non-C hepatocellular carcinoma and hepatitis B virus hepatocellular carcinoma from non-cirrhotic liver. J Surg Oncol. 2014;110:976–981.CrossRefPubMedGoogle Scholar
  14. 14.
    Kim JM, Kwon CH, Joh JW, Park JB, Lee JH, Kim SJ, Paik SW, Park CK, Yoo BC. Differences between hepatocellular carcinoma and hepatitis B virus infection in patients with and without cirrhosis. Ann Surg Oncol. 2014;21:458–465.CrossRefPubMedGoogle Scholar
  15. 15.
    Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462–503.CrossRefPubMedGoogle Scholar
  16. 16.
    Kim JM, Kwon CH, Joh JW, Park JB, Ko JS, Lee JH, Kim SJ, Park CK. The effect of alkaline phosphatase and intrahepatic metastases in large hepatocellular carcinoma. World J Surg Oncol. 2013;11:40.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    European Association for the Study of the Liver. Electronic address eee. EASL Clinical Practice Guidelines: Liver transplantation. J Hepatol. 2016;64:433–485.CrossRefGoogle Scholar
  18. 18.
    Tranchart H, Chirica M, Sepulveda A, Massault PP, Conti F, Scatton O, Soubrane O. Long-term outcomes following aggressive management of recurrent hepatocellular carcinoma after upfront liver resection. World J Surg. 2012;36:2684–2691.CrossRefPubMedGoogle Scholar
  19. 19.
    Fuks D, Dokmak S, Paradis V, Diouf M, Durand F, Belghiti J. Benefit of initial resection of hepatocellular carcinoma followed by transplantation in case of recurrence: an intention-to-treat analysis. Hepatology. 2012;55:132–140.CrossRefPubMedGoogle Scholar
  20. 20.
    Kitamura K, Hatano E, Higashi T, Seo S, Nakamoto Y, Yamanaka K, Iida T, Taura K, Yasuchika K, Uemoto S. Preoperative FDG-PET predicts recurrence patterns in hepatocellular carcinoma. Ann Surg Oncol. 2012;19:156–162.CrossRefPubMedGoogle Scholar
  21. 21.
    Zhang W, Lai SL, Chen J, Xie D, Wu FX, Jin GQ, Su DK. Validated preoperative computed tomography risk estimation for postoperative hepatocellular carcinoma recurrence. World J Gastroenterol. 2017;23:6467–6473.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kim AY, Sinn DH, Jeong WK, Kim YK, Kang TW, Ha SY, Park CK, Choi GS, Kim JM, Kwon CHD, Joh JW, Kim MJ, Sohn I, Jung SH, Paik SW, Lee WJ. Hepatobiliary MRI as novel selection criteria in liver transplantation for hepatocellular carcinoma. J Hepatol. 2018;68:1144–1152.CrossRefPubMedGoogle Scholar
  23. 23.
    Sapisochin G, Castells L, Dopazo C, Bilbao I, Minguez B, Lazaro JL, Allende H, Balsells J, Caralt M, Charco R. Single HCC in cirrhotic patients: liver resection or liver transplantation? Long-term outcome according to an intention-to-treat basis. Ann Surg Oncol. 2013;20:1194–1202.CrossRefPubMedGoogle Scholar
  24. 24.
    Bhangui P, Allard MA, Vibert E, Cherqui D, Pelletier G, Cunha AS, Guettier C, Vallee JC, Saliba F, Bismuth H, Samuel D, Castaing D, Adam R. Salvage Versus Primary Liver Transplantation for Early Hepatocellular Carcinoma: Do Both Strategies Yield Similar Outcomes? Ann Surg. 2016;264:155–163.CrossRefPubMedGoogle Scholar
  25. 25.
    Ho CM, Wu CY, Lee PH, Lai HS, Ho MC, Wu YM, Hu RH. Analysis of the risk factors of untransplantable recurrence after primary curative resection for patients with hepatocellular carcinoma. Ann Surg Oncol. 2013;20:2526–2533.CrossRefPubMedGoogle Scholar
  26. 26.
    Lee HW, Suh KS. Liver transplantation for advanced hepatocellular carcinoma. Clin Mol Hepatol. 2016;22:309–318.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2019

Authors and Affiliations

  1. 1.Department of Surgery, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  2. 2.Division of HBP Surgery, Department of SurgerySeoul National University College of MedicineSeoulRepublic of Korea
  3. 3.Department of BiostaticsSamsung Medical CenterSeoulRepublic of Korea

Personalised recommendations