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Annals of Surgical Oncology

, Volume 18, Issue 13, pp 3632–3639 | Cite as

Locoregional Therapy-Induced Tumor Necrosis as a Predictor of Recurrence after Liver Transplant in Patients with Hepatocellular Carcinoma

  • Meng-Hsing Ho
  • Chih-Yung Yu
  • Kuo-Piao Chung
  • Teng-Wei Chen
  • Heng-Cheng Chu
  • Chih-Kung Lin
  • Chung-Bao Hsieh
Hepatobiliary Tumors

Abstract

Background

Patients with hepatocellular carcinoma (HCC) often undergo locoregional therapy before liver transplant either to downstage the tumor or as bridge therapy. Our goal was to assess the risk factors for posttransplant tumor recurrence, specifically the extent of necrosis induced by locoregional therapy.

Methods

We conducted a hospital-based retrospective analysis of 100 patients with HCC who received a liver transplant, 86 of whom had received pretransplant locoregional therapy. We evaluated various patient- and tumor-related parameters to determine the risk factors for recurrence. Furthermore, we grouped patients by the degree of tumor necrosis after locoregional therapy and identified the factors that were associated with a favorable tumor response.

Results

Initial tumor extent beyond the University of San Francisco (UCSF) criteria, microvascular invasion, and attainment of less than 90% tumor necrosis after locoregional therapy were independent risk factors for tumor recurrence. In addition, there was a significant correlation between the tumor necrosis percentage and disease-specific survival rate. Among patients whose tumors initially exceeded the UCSF criteria, those with extensive locoregional therapy-induced tumor necrosis had lower recurrence rates. All recurrences after transplant occurred within 3 years, and recurrence rates in patients with extensive tumor necrosis at 1, 2, and 3 years were 3%, 6%, and 10%, respectively. Female gender and a solitary tumor were independently associated with extensive tumor necrosis.

Conclusions

In HCC patients who are transplant candidates and undergo pretransplant locoregional therapy, the degree of induced tumor necrosis affects both tumor recurrence and survival rate.

Keywords

Liver Transplantation Tace Dynamic Compute Tomography Locoregional Therapy Microvascular Invasion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94:153–56.PubMedCrossRefGoogle Scholar
  2. 2.
    El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999;340:745–50.PubMedCrossRefGoogle Scholar
  3. 3.
    Wakabayashi H, Ushiyama T, Ishimura K, et al. Significance of reduction surgery in multidisciplinary treatment of advanced hepatocellular carcinoma with multiple intrahepatic lesions. J Surg Oncol. 2003;82:98–103.PubMedCrossRefGoogle Scholar
  4. 4.
    Kim WR, Brown RS Jr. Terrault NA, El Serag H. Burden of liver disease in the United States: summary of a workshop. Hepatology. 2002;36:227–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinoma in patients with cirrhosis. N Engl J Med. 1996;334:693–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Jonas S, Bechstein WO, Steinmuller T, et al. Vascular invasion an histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33:1080–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33:1394–403.PubMedCrossRefGoogle Scholar
  8. 8.
    Mor E, Kaspa RT, Sheiner P, Schwartz M. Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation. Ann Intern Med. 1998;129:643–53.PubMedGoogle Scholar
  9. 9.
    Ota K, Teraoka S, Kawai T. Donor difficulties in Japan and Asian countries. Transpl Proc. 1995;27:83–6.Google Scholar
  10. 10.
    Mazziotti A, Grazi GL, Cavallari A. Surgical treatment of hepatocellular carcinoma on cirrhosis: a Western experience. Hepatogastroenterology. 1998;45:1281–7.PubMedGoogle Scholar
  11. 11.
    Toso C, Mentha G, Kneteman NM, Majno P. The place of downstaging for hepatocellular carcinoma. J Hepatol. 2010;52:930–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Oldhafer KJ, Chavan A, Fruhauf NR, et al. Aterial chemoembolization before liver transplantation in patients with hepatocellular carcinoma: marked tumor necrosis, but no survival benefit? J Hepatol. 1998;29:953–99.PubMedCrossRefGoogle Scholar
  13. 13.
    Decaens T, Roudot-Thoraval F, Bresson-Hadni S, et al. Impact of pretransplantation transarterial chemoembolization on survival and recurrence after liver transplantation for hepatocellular carcinoma. Liver Transpl. 2005;11:767–75.PubMedCrossRefGoogle Scholar
  14. 14.
    Porrett PM, Peterman H, Rosen M, et al. Lack of benefit of pre-transplant locoregional hapatic therapy for hepatocellular cancer in the current MELD era. Liver Transpl. 2006;12:665–73.PubMedCrossRefGoogle Scholar
  15. 15.
    Lesurtel M, Mullhaupt B, Pestalozzi BC, Pfammatter T, Clavien PA. Transarterial chemoembolization as a bridge to liver transplantation for hepatocellular carcinoma: an evidence-based analysis. Am J Transplant. 2006;6:2644–50.PubMedCrossRefGoogle Scholar
  16. 16.
    Poon RT, Ngan H, Lo CM, Liu CL, Fan ST, Wong J. Transarterial chemoembolization for inoperable hepatocellular carcinoma and postresection intrahepatic recurrence. J Surg Oncol. 2000;73:109–14.PubMedCrossRefGoogle Scholar
  17. 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;48:819–27.PubMedCrossRefGoogle Scholar
  18. 18.
    Harnois DM, Steers J, Andrew JC, et al. Preoperative hepatic artery chemoembolization followed by orthotopic liver transplantation for hepatocellular carcinoma. Liver Transpl Surg. 1999;5:192–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Roayaie S, Frischer JS, Emre SH, et al. Long-term results with multimodal adjuvant therapy and liver transplantation for the treatment of hepatocellular carcinomas larger than 5 centimeters. Ann Surg. 2002;235:533–9.PubMedCrossRefGoogle Scholar
  20. 20.
    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;9:557–63.PubMedCrossRefGoogle Scholar
  21. 21.
    Bharat A, Brown DB, Crippin JS, et al. Pre-liver transplantation locoregional adjuvant therapy for hepatocellular carcinoma as a strategy to improve longterm survival. J Am Coll Surg. 2006;203:411–20.PubMedCrossRefGoogle Scholar
  22. 22.
    Wong LL, Tanaka K, Lau L, Komura S. Pre-transplant treatment of hepatocellular carcinoma: assessment of tumor necrosis in explanted livers. Clin Tanspl. 2004: 18:227–34.CrossRefGoogle Scholar
  23. 23.
    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;8:2547–57.PubMedCrossRefGoogle Scholar
  24. 24.
    Toso C, Asthana S, Bigam DL, Shapiro AM, Kneteman NM. Reassessing selection criteria prior to liver transplantation for hepatocellular carcinoma utilizing the Scientific Registry of transplant recipients database. Hepatology. 2009;49:832–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Toso C, Trotter J, Wei A, et al. Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma. Liver Transpl. 2008;14:1107–15.PubMedCrossRefGoogle Scholar
  26. 26.
    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;13:272–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Gerd Otto, Sascha Herber, Michael Heise, et al. Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma. Liver Transpl. 2006;12;1260–7.CrossRefGoogle Scholar
  28. 28.
    Yao FY, Kinkhabwala M, LaBerge JM, et al. The impact of pre-operative loco-regional therapy on outcome after liver transplantation for hepatocellular carcinoma. Am J Transplant. 2005;5:795–804.PubMedCrossRefGoogle Scholar
  29. 29.
    Regalia E, Coppa J, Pulvirenti R, et al. Liver transplantation for small hepatocellular carcinoma in cirrhosis: analysis of our experience. Transpl Proc. 2001;33:1442–4.CrossRefGoogle Scholar
  30. 30.
    Yao FY, Xiao L, Bass NM, Kerlan R, Ascher NL, Roberts JP. Liver transplantation for hepatocellular carcinoma: validation of the UCSF-expanded criteria based on preoperative imaging. Am J Transplant. 2007;7:2587–96.PubMedCrossRefGoogle Scholar
  31. 31.
    Pawlik TM, Delman KA, Vauthey JN, et al. Tumor size predicts vascular invasion and histologic grade: Implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl. 2005;11:1086–92.PubMedCrossRefGoogle Scholar
  32. 32.
    Kim BK, Han KH, Park YN, et al. Prediction of microvascular invasion before curative resection of hepatocellular carcinoma. J Surg Oncol. 2008;97:246–52.PubMedCrossRefGoogle Scholar
  33. 33.
    Lim JH, Choi D, Park CK, Lee WJ, Lim HK. Encapsulated hepatocellular carcinoma: CT-pathologic correlations. Eur Radiol. 2006;16:2326–33.PubMedCrossRefGoogle Scholar
  34. 34.
    Hsieh CB, Chen TW, Chu CM, Chu HC, Yu CP, Chung KP. Is inconsistency of alpha-fetoprotein level a good prognosticator for hepatocellular carcinoma recurrence? World J Gastroenterol. 2010;16:3049–55.PubMedCrossRefGoogle Scholar
  35. 35.
    Yamamoto K, Imamura H, Matsuyama Y, et al. Significance of alpha-fetoprotein and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma undergoing hepatectomy. Ann Surg Oncol. 2009;16:2795–804.PubMedCrossRefGoogle Scholar
  36. 36.
    Lo CM, Fan ST, Liu CL, et al. Living donor versus deceased donor liver transplantation for early irresectable hepatocellular carcinoma. Br J Surg. 2007;94:78–86.PubMedCrossRefGoogle Scholar
  37. 37.
    Kulik L, Abecassis M. Living donor liver transplantation for hepatocellular carcinoma. Gastroenterology. 2004;127:S277–82.PubMedCrossRefGoogle Scholar
  38. 38.
    Mazzaferro V, Chun YS, Poon RT, et al. Liver transplantation for hepatocellular carcinoma. Ann Surg Oncol. 2008;15:1001–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Man K, Ng KT, Lo CM, et al. Ischemia-reperfusion of small liver remnant promotes liver tumor growth and metastases-activation of cell invasion and migration pathways. Liver Transpl. 2007;13:1669–77.PubMedCrossRefGoogle Scholar
  40. 40.
    Man K, Fan ST, Lo CM, et al. Graft injury in relation to graft size in right lobe live donor liver transaplantation: a study of hepatic sinusoidal injury in correlation with portal hemodynamics and intragraft gene expression. Ann Surg. 2003;237:256–64.PubMedGoogle Scholar
  41. 41.
    Wands J. Hepatocellular carcinoma and sex. N Engl J Med. 2007;357:1974–76.PubMedCrossRefGoogle Scholar
  42. 42.
    Dohmen K, Shigematsu H, Irie K and Ishibashi H. Longer survival in female than male with hepatocellular carcinoma. J Gastroenterol Hepatol. 2003;18:267–72.PubMedCrossRefGoogle Scholar
  43. 43.
    Naugler WE, Sakurai T, Kim S, et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 2007;317:121–4.PubMedCrossRefGoogle Scholar
  44. 44.
    Shim JH, Kim KM, Lee YJ, et al. Complete necrosis after transarterial chemoembolization could predict prolonged survival in patients with recurrent intrahepatic hepatocellular carcinoma after curative resection. Ann Surg Oncol. 2010;17:869–77.PubMedCrossRefGoogle Scholar
  45. 45.
    Kim SH, Lee WJ, Lim HK and Lim JH. Prediction of viable tumor in hepatocellular carcinoma treated with transcatheter arterial chemoembolization: usefulness of attenuation value measurement at quadruple-phase helical computed tomography. J Comput Assist Tomogr. 2007;31:198–203.PubMedCrossRefGoogle Scholar
  46. 46.
    Kamel IR, Bluemke DA, Eng J, et al. The role of functional MR imaging in the assessment of tumor response after chemoembolization in patients with hepatocellular carcinoma. J Vasc Interv Radiol. 2006;17:505–12.PubMedCrossRefGoogle Scholar
  47. 47.
    Kloeckner R, Otto G, Biesterfeld S, et al. MDCT versus MRI assessment of tumor response after transarterial chemoembolization for the treatment of hepatocellular carcinoma. Cardiovasc Intervent Radiol. 2010;33:532–40.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Meng-Hsing Ho
    • 1
  • Chih-Yung Yu
    • 2
  • Kuo-Piao Chung
    • 3
  • Teng-Wei Chen
    • 1
  • Heng-Cheng Chu
    • 4
  • Chih-Kung Lin
    • 5
  • Chung-Bao Hsieh
    • 1
    • 3
  1. 1.Division of General Surgery, Department of SurgeryTri-Service General Hospital, National Defense Medical CenterTaipeiTaiwan
  2. 2.Department of RadiologyTri-Service General Hospital, National Defense Medical CenterTaipeiTaiwan
  3. 3.Institute of Health Policy and ManagementNational Taiwan UniversityTaipeiTaiwan
  4. 4.Division of Gastroenterology, Department of MedicineTri-Service General Hospital, National Defense Medical CenterTaipeiTaiwan
  5. 5.Department of PathologyTri-Service General Hospital, National Defense Medical CenterTaipeiTaiwan

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