Surgical Management of Hepatocellular Carcinoma (HCC)

간세포암의 외과적 치료

  • Lee, Kuhn-Uk (Department of Surgery, Seoul National University College of Medicine)
  • 이건욱 (서울대학교 의과대학 외과학교실)
  • Published : 2010.09.30

Abstract

The European Association for the Study of the Liver (EASL) in 2001 and the American Association for Liver Diseases (AASLD) in 2005 followed the Barcelona - Clinic Liver Cancer (BCLC) staging classification and treatment schedule. Surgical resection can be offered for patients who have a single lesion if they are not cirrhotic or have cirrhosis and still have well-preserved liver function, normal bilirubin and hepatic vein pressure <10 mmHg (level II). But the Japanese Practice Guideline reported by the Japanese Society of Hepatology in 2007 recommended surgical resection for 2 or 3 tumors no more than 3 cm in diameter, even in cases with 4 or more lesions. The differences in practice guidelines between these two areas come from different cultural situations, especially in the availability of transplantation. Our results from hepatic resection in 834 patients with HCC from 1992 to 2004 at Seoul National University Hospital were as follows: 1) After surgical resection, the favorable prognostic group are patients with tumor size less than 10 cm in size without major vessel invasion. 2) Surgical resection is recommended in the favorable group of patients with oligonodular tumors. 3) Surgical resection is not indicated for patients with major vessel tumor invasion or portal hypertension. In the AASLD guidelines, liver transplantation is an effective option for patients with HCC, corresponding to the Milan criteria: solitary <5 cm or up to three nodules <3 cm (level II), and a living donor transplantation can be offered for HCC if the waiting time is long enough to allow tumor progression leading to exclusion from the waiting list (level II). Japanese Practice Guidelines restrict liver transplantation to patients under the age of 65. The role of salvage liver transplantation is still controversial. Early detection and the development of therapeutic agents for metastases by microvascular tumor invasion are important for increasing survival of HCC patients.

Keywords

References

  1. Cho YB, Lee KU, Suh KS, et al. Hepatic resection compared to percutaneous ethanol injection for small hepatocellular carcinoma using propensity score matching. J Gastroenterol Hepatol 2007;22:1643-1649. https://doi.org/10.1111/j.1440-1746.2007.04902.x
  2. Wang HJ, Lee H. Surgical treatment of hepatocellular carcinoma. Korean J Gastroenterol 2005;45:247-257.
  3. Cha CH, Ruo L, Fong Y, et al. Resection of hepatocellular carcinoma in patients otherwise eligible for transplantation. Ann Surg 2003;238:315-321.
  4. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907-1917. https://doi.org/10.1016/S0140-6736(03)14964-1
  5. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 1999;30:1434- 1440. https://doi.org/10.1002/hep.510300629
  6. 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. https://doi.org/10.1056/NEJM199603143341104
  7. Yi NJ, Suh KS, Kim T, Kim J, Shin WY, Lee KU. Current role of surgery in treatment of early stage hepatocellular carcinoma: resection versus liver transplantation. Oncology 2008; 75(Suppl 1):124-128. https://doi.org/10.1159/000173434
  8. Suh KS, Cho EH, Lee HW, Shin WY, Yi NJ, Lee KU. Liver transplantation for hepatocellular carcinoma in patients who do not meet the Milan criteria. Dig Dis 2007;25:329-333. https://doi.org/10.1159/000106913
  9. Llovet JM, Fuster J, Bruix J, Barcelona-Clínic Liver Cancer Group. The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl 2004; 10(2 Suppl 1):S115-S120. https://doi.org/10.1002/lt.20034
  10. Cho YB, Lee KU, Lee HW, et al. Outcomes of hepatic resection for a single large hepatocellular carcinoma. World J Surg 2007;31:795-801. https://doi.org/10.1007/s00268-006-0359-z
  11. Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona- 2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001;35:421-430. https://doi.org/10.1016/S0168-8278(01)00130-1
  12. Bruix J, Sherman M, Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology 2005;42: 1208-1236. https://doi.org/10.1002/hep.20933
  13. National Comprehensive Cancer Network. NCCN Clinical Practice Guidlines in Onclolgy. Hepatobiliary cancer. Available at www.nccn.org. Assessed 2009
  14. Tsai TJ, Chau GY, Lui WY, et al. Clinical significance of microscopic tumor venous invasion in patients with resectable hepatocellular carcinoma. Surgery 2000;127:603-608. https://doi.org/10.1067/msy.2000.105498
  15. Pawlik TM, Poon RT, Abdalla EK, et al, International Cooperative Study Group on Hepatocellular Carcinoma. Critical appraisal of the clinical and pathologic predictors of survival after resection of large hepatocellular carcinoma. Arch Surg 2005;140:450-457. https://doi.org/10.1001/archsurg.140.5.450
  16. Delis SG, Bakoyiannis A, Tassopoulos N, et al. Hepatic resection for large hepatocellular carcinoma in the era of UCSF criteria. HPB (Oxford) 2009;11:551-558. https://doi.org/10.1111/j.1477-2574.2009.00084.x
  17. Abdalla EK, Denys A, Hasegawa K, et al. Treatment of large and advanced hepatocellular carcinoma. Ann Surg Oncol 2008;15:979-985. https://doi.org/10.1245/s10434-007-9727-7
  18. Vauthey JN, Lauwers GY, Esnaola NF, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol 2002; 20:1527-1536. https://doi.org/10.1200/JCO.20.6.1527
  19. Shoup M, Gonen M, D'Angelica M, et al. Volumetric analysis predicts hepatic dysfunction in patients undergoing major liver resection. J Gastrointest Surg 2003;7:325-330. https://doi.org/10.1016/S1091-255X(02)00370-0
  20. Poon RT. Optimal initial treatment for early hepatocellular carcinoma in patients with preserved liver function: transplantation or resection? Ann Surg Oncol 2007;14:541-547. https://doi.org/10.1245/s10434-006-9156-z
  21. Llovet JM, Bruix J, Gores GJ. Surgical resection versus transplantation for early hepatocellular carcinoma: clues for the best strategy. Hepatology 2000;31:1019-1021. https://doi.org/10.1053/he.2000.6959
  22. Korean Liver Cancer Study Group and National Cancer Center, Korea. Practice guidelines for management of hepatocellular carcinoma 2009. Korean J Hepatol 2009;15: 391-423. https://doi.org/10.3350/kjhep.2009.15.3.391
  23. Makuuchi M, Kokudo N. Clinical practice guidelines for hepatocellular carcinoma: the first evidence based guidelines from Japan. World J Gastroenterol 2006;12:828-829. https://doi.org/10.3748/wjg.v12.i5.828
  24. Kudo M, Okanoue T. Japan Society of Hepatology. Management of hepatocellular carcinoma in Japan: consensus-based clinical practice manual proposed by the Japan Society of Hepatology. Oncology 2007;72(Suppl 1):2-15.
  25. United Network for Organ Sharing. Organ donation and Transplantation. Available at:www.unos.org
  26. Sarasin FP, Majno PE, Llovet JM, Bruix J, Mentha G, Hadengue A. Living donor liver transplantation for early hepatocellular carcinoma: a life-expectancy and cost-effectiveness perspective. Hepatology 2001;33:1073-1079. https://doi.org/10.1053/jhep.2001.23311
  27. 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- 1403. https://doi.org/10.1053/jhep.2001.24563
  28. Mazzaferro V, Chun YS, Poon RT, et al. Liver transplantation for hepatocellular carcinoma. Ann Surg Oncol 2008;15:1001- 1007. https://doi.org/10.1245/s10434-007-9559-5
  29. Volk M, Marrero JA. Liver transplantation for hepatocellular carcinoma: who benefits and who is harmed? Gastroenterology 2008;134:1612-1614. https://doi.org/10.1053/j.gastro.2008.03.042
  30. Majno PE, Sarasin FP, Mentha G, Hadengue A. Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: an outcome-oriented decision analysis. Hepatology 2000;31:899-906. https://doi.org/10.1053/he.2000.5763
  31. Bismuth H, Chiche L, Adam R, Castaing D, Diamond T, Dennison A. Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients. Ann Surg 1993; 218:145-151. https://doi.org/10.1097/00000658-199308000-00005
  32. Park YK, Kim BW, Wang HJ, Kim MW. Hepatic resection for hepatocellular carcinoma meeting Milan criteria in Child-Turcotte-Pugh class a patients with cirrhosis. Transplant Proc 2009;41:1691-1697. https://doi.org/10.1016/j.transproceed.2008.07.146
  33. Cherqui D, Laurent A, Mocellin N, et al. Liver resection for transplantable hepatocellular carcinoma: long-term survival and role of secondary liver transplantation. Ann Surg 2009; 250:738-746. https://doi.org/10.1097/SLA.0b013e3181bd582b
  34. Sala M, Fuster J, Llovet JM, et al, Barcelona Clinic Liver Cancer (BCLC) Group. High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation. Liver Transpl 2004;10:1294-1300. https://doi.org/10.1002/lt.20202
  35. Portolani N, Coniglio A, Ghidoni S, et al. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg 2006;243: 229-235. https://doi.org/10.1097/01.sla.0000197706.21803.a1
  36. Shirabe K, Itoh S, Yoshizumi T, et al. The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma-with special reference to the serum levels of des-gamma-carboxy prothrombin. J Surg Oncol 2007;95:235-240. https://doi.org/10.1002/jso.20655
  37. Durazo FA, Blatt LM, Corey WG, et al. Des-gamma- carboxyprothrombin, alpha-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol 2008;23:1541-1548. https://doi.org/10.1111/j.1440-1746.2008.05395.x
  38. Tsai WC, Hsu PW, Lai TC, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology 2009;49:1571-1582. https://doi.org/10.1002/hep.22806
  39. Wong CC, Wong CM, Tung EK, Man K, Ng IO. Rho-kinase 2 is frequently overexpressed in hepatocellular carcinoma and involved in tumor invasion. Hepatology 2009;49:1583- 1594. https://doi.org/10.1002/hep.22836
  40. Kamiyama T, Takahashi M, Nakagawa T, et al. AFP mRNA detected in bone marrow by real-time quantitative RT-PCR analysis predicts survival and recurrence after curative hepatectomy for hepatocellular carcinoma. Ann Surg 2006;244:451-463.
  41. Halazun KJ, Hardy MA, Rana AA, et al. Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma. Ann Surg 2009;250: 141-151. https://doi.org/10.1097/SLA.0b013e3181a77e59
  42. Schwartz JD, Schwartz M, Mandeli J, Sung M. Neoadjuvant and adjuvant therapy for resectable hepatocellular carcinoma: review of the randomised clinical trials. Lancet Oncol 2002; 3:593-603. https://doi.org/10.1016/S1470-2045(02)00873-2
  43. Lau WY, Leung TW, Ho SK, et al. Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial. Lancet 1999;353: 797-801. https://doi.org/10.1016/S0140-6736(98)06475-7
  44. Takayama T, Sekine T, Makuuchi M, et al. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet 2000;356:802- 807. https://doi.org/10.1016/S0140-6736(00)02654-4
  45. Muto Y, Moriwaki H, Ninomiya M, et al. Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group. N Engl J Med 1996;334:1561-1567. https://doi.org/10.1056/NEJM199606133342402
  46. Ikeda K, Arase Y, Saitoh S, et al. Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor-A prospective randomized study of hepatitis C virus-related liver cancer. Hepatology 2000;32:228-232.
  47. Kubo S, Nishiguchi S, Hirohashi K, Tanaka H, Shuto T, Kinoshita H. Randomized clinical trial of long-term outcome after resection of hepatitis C virus-related hepatocellular carcinoma by postoperative interferon therapy. Br J Surg 2002;89:418-422. https://doi.org/10.1046/j.0007-1323.2001.02054.x