Skip to main content
SpringerLink
Log in

Does Microvascular Invasion Affect Outcomes After Liver Transplantation for HCC? A Histopathological Analysis of 155 Consecutive Explants

  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Macroscopic vascular invasion (macroVI) is associated with poor outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). Whether microvascular invasion (microVI) is associated with the same adverse prognosis is unclear. One hundred and fifty-five consecutive patients with confirmed HCC after LT from March 1991 to 2004 at our institution were reviewed. Patients had to satisfy Milan criteria to be accepted for LT. They were followed with surveillance images every 3 months while on the waiting list. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan–Meier analysis. Demographic, tumor, and histopathologic characteristics were tested for their prognostic significance. Median follow-up after LT was 30 months. Overall graft survival rates were 87, 74, and 65% at 1, 3, and 5 years, respectively. All recurrences (22/155, 14%) developed within 4 years after LT with an overall 5-year DFS of 79%. Vascular invasion, either microVI or macroVI, was more likely in patients with multicentric HCC (n ≥ 3, p < 0.001) and larger tumor size >4 cm (p = 0.04). Tumor size >5 cm (p = 0.04), advanced pathological TMN stage (p = 0.007), microVI (p = 0.001), and macroVI (p < 0.001) predicted poor tumor-free survival on univariate analysis, but only macroVI was significant in multivariate analysis (hazard ratio 54.2, 95% confidence interval 11, 266). Furthermore, only macroVI was a significant predictor of mortality after LT (p = 0.01). Macrovascular invasion is strongly associated with high rates of recurrence and diminished survival after LT whereas microVI is not an independent risk factor.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334:693–699.

    Article  PubMed  CAS  Google Scholar 

  2. Yao FY, Roberts JP. Applying expanded criteria to liver transplantation for hepatocellular carcinoma: Too much too soon, or is now the time? Liver Transpl 2004;10:919–921.

    Article  Google Scholar 

  3. Yao FY, Ferrell L, Bass NM, Bacchetti P, Ascher NL, Roberts JP. 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.

    Article  Google Scholar 

  4. Marsh JW, Dvorchik I, Bonham CA, Iwatsuki S. Is the pathologic TNM staging system for patients with hepatoma predictive of outcome? Cancer 2000;88:538–543.

    Article  PubMed  CAS  Google Scholar 

  5. Shah SA, Greig PD, Gallinger S, Cattral MS, Dixon E, Kim RD, Taylor BR, Grant DR, Vollmer CM. Factors associated with early recurrence after resection for hepatocellular carcinoma and outcomes. J Am Coll Surg 2006;202:275–283.

    Article  PubMed  Google Scholar 

  6. Kosuge T, Makuuchi M, Takayama T, Yamamoto J, Shimada K, Yamasaki S. Long-term results after resection of hepatocellular carcinoma: Experience of 480 cases. Hepatogastroenterology 1993;40:328–332.

    PubMed  CAS  Google Scholar 

  7. Izumi R, Shimizu K, Ii T, Yagi M, Matsui O, Nonomura A, Miyazaki I. Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection. Gastroenterology 1994;106:720–727.

    PubMed  CAS  Google Scholar 

  8. Iwatsuki S, Dvorchik I, Marsh JW, Madariaga JR, Carr B, Fung JJ, Starzl TE. Liver transplantation for hepatocellular carcinoma: A proposal of a prognostic scoring system. J Am Coll Surg 2000;191:389–394.

    Article  PubMed  CAS  Google Scholar 

  9. Hemming AW, Cattral MS, Reed AI, Van Der Werf WJ, Greig PD, Howard RJ. Liver transplantation for hepatocellular carcinoma. Ann Surg 2001;233:652–659.

    Article  PubMed  CAS  Google Scholar 

  10. Otto G, Heuschen U, Hofmann WJ, Krumm G, Hinz U, Herfarth C. Survival and recurrence after liver transplantation versus liver resection for hepatocellular carcinoma: A retrospective analysis. Ann Surg 1998;227:424–432.

    Article  PubMed  CAS  Google Scholar 

  11. Jonas S, Bechstein WO, Steinmuller T, Herrmann M, Radke C, Berg T, Settmacher U, Neuhaus P. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology 2001;33:1080–1086.

    Article  PubMed  CAS  Google Scholar 

  12. Pawlik TM, Poon RT, Abdalla EK, Zorzi D, Ikai I, Curley SA, Nagorney DM, Belghiti J, Ng IO, Yamaoka Y, Lauwers GY, Vauthey JN. Critical appraisal of the clinical and pathologic predictors of survival after resection of large hepatocellular carcinoma. Arch Surg 2005;140;450–457.

    Article  PubMed  Google Scholar 

  13. Esnaola NF, Lauwers GY, Mirza NQ, Nagorney DM, Doherty D, Ikai I, Yamaoka Y, Regimbeau JM, Belghiti J, Curley SA, Ellis LM, Vauthey JN. Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation. J Gastrointest Surg 2002;6:224–232.

    Article  PubMed  Google Scholar 

  14. Shetty K, Timmins K, Brensinger C, Furth EE, Rattan S, Sun W, Rosen M, Soulen M, Shaked A, Reddy KR, Olthoff KM. Liver transplantation for hepatocellular carcinoma validation of present selection criteria in predicting outcome. Liver Transpl 2004; 10:911–918.

    Article  Google Scholar 

  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. Tamura S, Kato T, Berho M, Misiakos EP, O’Brien C, Reddy KR, Nery JR, Burke GW, Schiff ER, Miller J, Tzakis AG. Impact of histological grade of hepatocellular carcinoma on the outcome of liver transplantation. Arch Surg 2001;136:25–30.

    Article  PubMed  CAS  Google Scholar 

  17. Yokoyama I, Sheahan DG, Carr B, Kakizoe S, Selby R, Tzakis AG, Todo S, Iwatsuki S, Starzl TE. Clinicopathologic factors affecting patient survival and tumor recurrence after orthotopic liver transplantation for hepatocellular carcinoma. Transplant Proc 1991;23:2194–2196.

    PubMed  CAS  Google Scholar 

  18. Befeler AS, Hayashi PH, Di Bisceglie AM. Liver transplantation for hepatocellular carcinoma. Gastroenterology 2005;128:1752–1764.

    Article  PubMed  Google Scholar 

  19. Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: Expansion of the tumor size limits does not adversely impact survival. Hepatology 2001;33:1394–1403.

    Article  PubMed  CAS  Google Scholar 

  20. Marsh JW, Finkelstein SD, Schwartz ME, Fiel MI, Dvorchik I. Advancing the diagnosis and treatment of hepatocellular carcinoma. Liver Transpl 2005;11:469–472.

    Article  Google Scholar 

  21. Lee JS, Chu IS, Heo J, Calvisi DF, Sun Z, Roskams T, Durnez A, Demetris AJ. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology 2004;40:667–676.

    Article  PubMed  CAS  Google Scholar 

  22. Marsh JW, Dvorchik I, Subotin M, Balan V, Rakela J, Popechitelev EP, Subbotin V, Casavilla A, Carr BI, Fung JJ, Iwatsuki S. The prediction of risk of recurrence and time to recurrence of hepatocellular carcinoma after orthotopic liver transplantation: A pilot study. Hepatology 1997;26:444–450.

    Article  PubMed  CAS  Google Scholar 

  23. Cillo U, Vitale A, Bassanello M, Boccagni P, Brolese A, Zanus G, D'Amico F, Ciarleglio FA, Boccagni P, Brolese A, Zanus G, D'Amico DF. Liver transplantation for the treatment of moderately or well-differentiated hepatocellular carcinoma. Ann Surg 2004;239:150–159.

    Article  PubMed  Google Scholar 

  24. Yao FY, Bass NM, Nikolai B, Davern TJ, Kerlan R, Wu V, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: Analysis of survival according to the intention-to-treat principle and dropout from the waiting list. Liver Transpl 2002;8:873–883.

    Article  Google Scholar 

  25. Cillo U, Bassanello M, Vitale A, Grigoletto FA, Burra P, Fagiuoli S, Burra P, Fagiuoli S, Farinati F, Rugge M, D'Amico DF. The critical issue of hepatocellular carcinoma prognostic classification: Which is the best tool available? J Hepatol 2004;40:124–131.

    Article  PubMed  Google Scholar 

  26. Schlitt HJ, Neipp M, Weimann A, Oldhafer KJ, Schmoll E, Boeker K, Nashan B, Kubicka S, Maschek H, Tusch G, Raab R, Ringe B, Manns MP, Pichlmayr R. Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation. J Clin Oncol 1999;17:324–331.

    PubMed  CAS  Google Scholar 

  27. Jaskolka JD, Asch MR, Kachura JR, Ho CS, Ossip M, Wong F, Sherman M, Grant DR, Greig PD, Gallinger S. Needle tract seeding after radiofrequency ablation of hepatic tumors. J Vasc Interv Radiol 2005;16:485–491.

    PubMed  Google Scholar 

  28. Majno PE, Adam R, Bismuth H, Castaing D, Ariche A, Krissat J, Perrin H, Azoulay D. Influence of preoperative c on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg 1997;226:688–701.

    Article  PubMed  CAS  Google Scholar 

  29. Stone MJ, Klintmalm GB, Polter D, Husberg BS, Mennel RG, Ramsay MA, Flemens ER, Goldstein RM. Neoadjuvant chemotherapy and liver transplantation for hepatocellular carcinoma: A pilot study in 20 patients. Gastroenterology 1993;104:196–202.

    PubMed  CAS  Google Scholar 

  30. Olthoff KM, Rosove MH, Shackleton CR, Imagawa DK, Farmer DG, Northcross P, Pakrasi AL, Martin P, Goldstein LI, Shaked A. Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma. Ann Surg 1995;221:734–741.

    Article  PubMed  CAS  Google Scholar 

  31. Carr BI, Selby R, Madariaga J, Iwatsuki S, Starzl TE. Prolonged survival after liver transplantation and cancer chemotherapy for advanced-stage hepatocellular carcinoma. Transplant Proc 1993;25:1128–1129.

    PubMed  CAS  Google Scholar 

  32. Pokorny H, Gnant M, Rasoul-Rockenschaub S, Gollackner B, Steiner B, Steger G, Steininger R, Muhlbacher F. Does additional doxorubicin chemotherapy improve outcome in patients with hepatocellular carcinoma treated by liver transplantation? Am J Transplant 2005;5:788–794.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Multi-Organ Transplantation Program, Toronto General Hospital, University Health Network, University of Toronto, 585 University Ave, 11C-1244, Toronto, ON, M5G 2N2, Canada

    Shimul A. Shah, Jensen C. C. Tan, Ian D. McGilvray, Mark S. Cattral, Gary A. Levy, Paul D. Greig & David R. Grant

Authors
  1. Shimul A. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jensen C. C. Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ian D. McGilvray
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark S. Cattral
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gary A. Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paul D. Greig
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. David R. Grant
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David R. Grant.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shah, S.A., Tan, J.C.C., McGilvray, I.D. et al. Does Microvascular Invasion Affect Outcomes After Liver Transplantation for HCC? A Histopathological Analysis of 155 Consecutive Explants. J Gastrointest Surg 11, 464–471 (2007). https://doi.org/10.1007/s11605-006-0033-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-006-0033-7

Keywords

Search

Navigation