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Journal of Gastrointestinal Cancer

, Volume 50, Issue 4, pp 808–815 | Cite as

Outcomes Following Resection of Hepatocellular Carcinoma in the Absence of Cirrhosis

  • Richard H. Lewis
  • Evan S. Glazer
  • David M. Bittenbinder
  • Thomas O’Brien
  • Jeremiah L. Deneve
  • David Shibata
  • Stephen W. Behrman
  • Jason M. Vanatta
  • Sanjaya K. Satapathy
  • Paxton V. DicksonEmail author
Original Research
  • 80 Downloads

Abstract

Background

Hepatocellular carcinoma (HCC) occasionally occurs in non-cirrhotic patients; however, outcomes for these patients are not extensively documented.

Methods

We performed an institutional review of patients without cirrhosis who underwent resection for HCC. Clinical data were evaluated to identify factors impacting recurrence-free survival (RFS) and overall survival (OS).

Results

Forty-two patients underwent hepatectomy for HCC in the absence of cirrhosis over a 10-year period. Median follow-up was 22 months. For the entire cohort, 1-, 3-, and 5-year RFS was 62%, 42%, and 38% and 1-, 3-, and 5-year OS was 78%, 60%, and 49%, respectively. On univariate analysis, RFS was significantly worse for patients with a disrupted/absent tumor capsule (p = 0.027), vascular invasion (p = 0.030), elevated alkaline phosphatase (p = 0.004), and tumor size > 10 cm (p = 0.016). OS was significantly worse for patients with a disrupted/absent tumor capsule (p = 0.044), obesity (p = 0.036), and elevated alkaline phosphatase (p = 0.007) with a trend towards decreased OS for tumor size > 10 cm (p = 0.07).

Conclusions

Patients undergoing resection for HCC in the absence of cirrhosis have fairly high recurrence and modest survival rates. Pre-operative alkaline phosphatase, tumor size, tumor encapsulation, and vascular invasion are important prognostic factors.

Keywords

Hepatocellular carcinoma Non-cirrhotic Surgery 

Notes

Compliance with Ethical Standards

This study did not receive any funding. No author has any financial conflict of interest. This article represents a retrospective review of an institutional experience and does not contain any studies with human participants performed by any of the authors.

References

  1. 1.
    Chacko S, Samanta S. Hepatocellular carcinoma: a life-threatening disease. Biomed Pharmacother. 2016;84:1679–88.CrossRefGoogle Scholar
  2. 2.
    Yoo HY, Patt CH, Geschwind JF, Thuluvath PJ. The outcome of liver transplantation in patients with hepatocellular carcinoma in the United States between 1988 and 2001: 5-year survival has improved significantly with time. J Clin Oncol. 2003;21(23):4329–35.CrossRefGoogle Scholar
  3. 3.
    Figueras J, Jaurrieta E, Valls C, Benasco C, Rafecas A, Xiol X, et al. Survival after liver transplantation in cirrhotic patients with and without hepatocellular carcinoma: a comparative study. Hepatology. 1997;25(6):1485–9.CrossRefGoogle Scholar
  4. 4.
    Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693–9.CrossRefGoogle Scholar
  5. 5.
    Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–96.CrossRefGoogle Scholar
  6. 6.
    Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. editors AJCC cancer staging manual. 7th ed. New York, Springer; 2009. p. 19–199.Google Scholar
  7. 7.
    Zhou Y, Lei X, Wu L, Wu X, Xu D, Li B. Outcomes of hepatectomy for noncirrhotic hepatocellular carcinoma: a systematic review. Surg Oncol. 2014;23(4):236–42.CrossRefGoogle Scholar
  8. 8.
    Cabibbo G, Craxì A. Epidemiology, risk factors and surveillance of hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 2010;14(4):352–5.PubMedGoogle Scholar
  9. 9.
    Yeh CN, Chen MF, Lee WC, Jeng LB. Prognostic factors of hepatic resection for hepatocellular carcinoma with cirrhosis: univariate and multivariate analysis. J Surg Oncol. 2002;81(4):195–202.CrossRefGoogle Scholar
  10. 10.
    Dahiya D, Wu TJ, Lee CF, Chan KM, Lee WC, Chen MF. Minor versus major hepatic resection for small hepatocellular carcinoma (HCC) in cirrhotic patients: a 20-year experience. Surgery. 2010;147(5):676–85.CrossRefGoogle Scholar
  11. 11.
    Menahem B, Lubrano J, Duvoux C, Mulliri A, Alves A, Costentin C, et al. Liver transplantation versus liver resection for hepatocellular carcinoma in intention to treat: attempt to perform an ideal meta-analysis. Liver Transpl. 2017;23:836–44.  https://doi.org/10.1002/lt.24758.CrossRefPubMedGoogle Scholar
  12. 12.
    Arnaoutakis DJ, Mavros MN, Shen F, Alexandrescu S, Firoozmand A, Popescu I, et al. Recurrence patterns and prognostic factors in patients with hepatocellular carcinoma in noncirrhotic liver: a multi-institutional analysis. Ann Surg Oncol. 2014;21(1):147–54.CrossRefGoogle Scholar
  13. 13.
    Bismuth H, Chiche L, Castaing D. Surgical treatment of hepatocellular carcinomas in noncirrhotic liver: experience with 68 liver resections. World J Surg. 1995;19(1):35–41.CrossRefGoogle Scholar
  14. 14.
    Dupont-Bierre E, Compagnon P, Raoul JL, Fayet G, de Lajarte-Thirouard AS, Boudjema K. Resection of hepatocellular carcinoma in noncirrhotic liver: analysis of risk factors for survival. J Am Coll Surg. 2005;201(5):663–70.CrossRefGoogle Scholar
  15. 15.
    Yu MC, Chan KM, Lee CF, Lee YS, Eldeen FZ, Chou HS, et al. Alkaline phosphatase: does it have a role in predicting hepatocellular carcinoma recurrence? J Gastrointest Surg. 2011;15(8):1440–9.CrossRefGoogle Scholar
  16. 16.
    Yip VS, Gomez D, Tan CY, Staettner S, Terlizzo M, Fenwick S, et al. Tumour size and differentiation predict survival after liver resection for hepatocellular carcinoma arising from non-cirrhotic and non-fibrotic liver: a case-controlled study. Int J Surg. 2013;11(10):1078–82.CrossRefGoogle Scholar
  17. 17.
    Faber W, Sharafi S, Stockmann M, Dennecke T, Bahra M, Klein F, et al. Patient age and extent of liver resection influence outcome of liver resection for hepatocellular carcinoma in non-cirrhotic liver. Hepato-Gastroenterology. 2014;61(135):1925–30.PubMedGoogle Scholar
  18. 18.
    Grazi GL, Cescon M, Ravaioli M, Ercolani G, Gardini A, Del Gaudio M, et al. Liver resection for hepatocellular carcinoma in cirrhotics and noncirrhotics. Evaluation of clinicopathologic features and comparison of risk factors for long-term survival and tumour recurrence in a single centre. Aliment Pharmacol Ther. 2003;17(Suppl 2):119–29.CrossRefGoogle Scholar
  19. 19.
    Faber W, Sharafi S, Stockmann M, Denecke T, Sinn B, Puhl G, et al. Long-term results of liver resection for hepatocellular carcinoma in noncirrhotic liver. Surgery. 2013;153(4):510–7.CrossRefGoogle Scholar
  20. 20.
    Truant S, Boleslawski E, Duhamel A, Bouras AF, Louvet A, Febvay C, et al. Tumor size of hepatocellular carcinoma in noncirrhotic liver: a controversial predictive factor for outcome after resection. Eur J Surg Oncol. 2012;38(12):1189–96.CrossRefGoogle Scholar
  21. 21.
    Yang LY, Fang F, Ou DP, Wu W, Zeng ZJ, Wu F. Solitary large hepatocellular carcinoma: a specific subtype of hepatocellular carcinoma with good outcome after hepatic resection. Ann Surg. 2009;249(1):118–23.CrossRefGoogle Scholar
  22. 22.
    Yang LY, Wang W, Peng JX, Yang JQ, Huang GW. Differentially expressed genes between solitary large hepatocellular carcinoma and nodular hepatocellular carcinoma. World J Gastroenterol. 2004;10(24):3569–73.CrossRefGoogle Scholar
  23. 23.
    Wu TH, Yu MC, Chen TC, Lee CF, Chan KM, Wu TJ, et al. Encapsulation is a significant prognostic factor for better outcome in large hepatocellular carcinoma. J Surg Oncol. 2012;105(1):85–90.CrossRefGoogle Scholar
  24. 24.
    Ng IO, Lai EC, Ng MM, Fan ST. Tumor encapsulation in hepatocellular carcinoma. A pathologic study of 189 cases. Cancer. 1992;70(1):45–9.CrossRefGoogle Scholar
  25. 25.
    Thorgeirsson SS, Grisham JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet. 2002;31(4):339–46.CrossRefGoogle Scholar
  26. 26.
    El-Refaie A, Savage K, Bhattacharya S, Khakoo S, Harrison TJ, El-Batanony M, et al. HCV-associated hepatocellular carcinoma without cirrhosis. J Hepatol. 1996;24(3):277–85.CrossRefGoogle Scholar
  27. 27.
    Trevisani F, Frigerio M, Santi V, Grignaschi A, Bernardi M. Hepatocellular carcinoma in non-cirrhotic liver: a reappraisal. Dig Liver Dis. 2010;42(5):341–7.CrossRefGoogle Scholar
  28. 28.
    Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer. 2006;6(9):674–87.CrossRefGoogle Scholar
  29. 29.
    White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol. 2012;10(12):1342–59.CrossRefGoogle Scholar
  30. 30.
    Perumpail RB, Wong RJ, Ahmed A, Harrison SA. Hepatocellular carcinoma in the setting of non-cirrhotic nonalcoholic fatty liver disease and the metabolic syndrome: US experience. Dig Dis Sci. 2015;60(10):3142–8.CrossRefGoogle Scholar
  31. 31.
    Siegel AB, Zhu AX. Metabolic syndrome and hepatocellular carcinoma: two growing epidemics with a potential link. Cancer. 2009;115(24):5651–61.CrossRefGoogle Scholar
  32. 32.
    Guzman G, Brunt EM, Petrovic LM, Chejfec G, Layden TJ, Cotler SJ. Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis? Arch Pathol Lab Med. 2008;132(11):1761–6.PubMedGoogle Scholar
  33. 33.
    Liu C, Sun L, Xu J, Zhao Y. Clinical efficacy of postoperative adjuvant transcatheter arterial chemoembolization on hepatocellular carcinoma. World J Surg Oncol. 2016;14:100.CrossRefGoogle Scholar
  34. 34.
    Mergental H, Adam R, Ericzon BG, Kalicinski P, Mühlbacher F, Höckerstedt K, et al. Liver transplantation for unresectable hepatocellular carcinoma in normal livers. J Hepatol. 2012;57(2):297–305.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Richard H. Lewis
    • 1
  • Evan S. Glazer
    • 1
    • 2
  • David M. Bittenbinder
    • 1
  • Thomas O’Brien
    • 3
  • Jeremiah L. Deneve
    • 1
    • 2
  • David Shibata
    • 1
    • 2
  • Stephen W. Behrman
    • 1
  • Jason M. Vanatta
    • 4
  • Sanjaya K. Satapathy
    • 5
  • Paxton V. Dickson
    • 1
    • 2
    Email author
  1. 1.Department of Surgery, Division of Surgical OncologyUniversity of Tennessee Health Science CenterMemphisUSA
  2. 2.West Cancer CenterMemphisUSA
  3. 3.Memphis Pathology GroupMemphisUSA
  4. 4.Transplant CenterCleveland Clinic Florida-WestonWestonUSA
  5. 5.Methodist University Transplant InstituteMemphisUSA

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