Abstract
Background
There is no clear consensus regarding the best treatment strategy for patients with advanced hepatocellular carcinoma (HCC).
Methods
Patients with cirrhosis and HCC beyond Milan who had undergone liver resection (LR) or primary orthotopic liver transplantation (OLT) between November 1995 and December 2005 were included in this study. Pathological tumor staging was based on the American Liver Tumor Study Group modified Tumor-Node-Metastasis classification.
Results
A total of 23 HCC patients were primarily treated by means of LR, 5 of whom eventually underwent salvage OLT. An additional 32 patients underwent primary OLT. The overall actuarial survival rates at 3 and 5 years were 35% after LR, and 69% and 60%, respectively, after primary OLT. Recurrence-free survival at 5 years was significantly higher after OLT (65%) than after LR (26%). Of the patients who underwent LR, 11 (48%) experienced HCC recurrence only in the liver; 6 of these 11 presented with advanced HCC recurrence, poor medical status, or short disease-free intervals and were not considered for transplantation. Salvage OLT was performed in 5 patients with early stage recurrence (45% of patients with hepatic recurrence after LR and 22% of all patients who underwent LR). At a median of 18 months after salvage OLT, all 5 patients are alive, 4 are free of disease, and 1 developed HCC recurrence 16 months after salvage OLT.
Conclusion
For patients with HCC beyond Milan criteria, multimodality treatment—including LR, salvage OLT, and primary OLT—results in long-term survival in half of the patients. When indicated, LR can optimize the use of scarce donor organs by leaving OLT as a reserve option for early stage HCC recurrence.
Similar content being viewed by others
References
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; 334:693–9
Cha CH, Ruo L, Fong Y, et al. Resection of hepatocellular carcinoma in patients otherwise eligible for transplantation. Ann Surg 2003; 238:315–23
Margarit C, Escartin A, Castells L, et al. Resection for hepatocellular carcinoma is a good option in Child-Turcotte-Pugh class A patients with cirrhosis who are eligible for liver transplantation. Liver Transpl 2005; 11:1242–51
Sala M, Fuster J, Llovet JM, et al. High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation. Liver Transpl 2004; 10:1294–300
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
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
Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 1999; 30:1434–40
Gondolesi GE, Roayaie S, Munoz L, et al. Adult living donor liver transplantation for patients with hepatocellular carcinoma: extending UNOS priority criteria. Ann Surg 2004; 239:142–9
Fong Y, Sun RL, Jarnagin W, et al. An analysis of 412 cases of hepatocellular carcinoma at a Western center. Ann Surg 1999; 229:790–9; discussion 799–800
Marsh JW, Dvorchik I. Liver organ allocation for hepatocellular carcinoma: are we sure? Liver Transpl 2003; 9:693–6
Pugh RN, Murray-Lyon IM, Dawson JL, et al. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973; 60:646–9
Goldsmith NA, Woodburne RT. The surgical anatomy pertaining to liver resection. Surg Gynecol Obstet 1957; 105:310–8
Couinaud C. Le foie: Etudes anatomiques et chirurgicales. Mason, Paris, 1957
Edmondson H SP. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer 1954; 1:462–503
United Network for Organ Sharing. Liver Transplant Candidates with hepatocellular carcinoma (HCC) Policy 3.6.4.4., 2002
Green F PD, Fleming I, et al., eds. Liver (including intrahepatic bile ducts). AJCC Cancer Staging Handbook. Springer, New York, 2002. pp. 131–44
Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22:696–9
Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003; 362:1907–17
Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003; 37:429–42
Bruix J, Llovet JM. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 2002; 35:519–24
Figueras J, Jaurrieta E, Valls C, et al. Resection or transplantation for hepatocellular carcinoma in cirrhotic patients: outcomes based on indicated treatment strategy. J Am Coll Surg 2000; 190:580–7
Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005; 42:1208–36
Llovet JM, Bruix J, Gores GJ. Surgical resection versus transplantation for early hepatocellular carcinoma: clues for the best strategy. Hepatology 2000; 31:1019–21
Sarasin FP, Giostra E, Mentha G, et al. Partial hepatectomy or orthotopic liver transplantation for the treatment of resectable hepatocellular carcinoma? A cost-effectiveness perspective. Hepatology 1998; 28:436–42
Belghiti J, Cortes A, Abdalla EK, et al. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg 2003; 238:885–93
Freeman RB, Wiesner RH, Edwards E, et al. Results of the first year of the new liver allocation plan. Liver Transpl 2004; 10:7–15
Shiffman ML, Saab S, Feng S, et al. Liver and intestine transplantation in the United States, 1995–2004. Am J Transplant 2006; 6:1170–87
Feng S, Buell JF, Cherikh WS, et al. Organ donors with positive viral serology or malignancy: risk of disease transmission by transplantation. Transplantation 2002; 74:1657–63
Porrett PM, Peterman H, Rosen M, et al. Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era. Liver Transpl 2006; 12:665–73
Llovet JM, Mas X, Aponte JJ, et al. Cost effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation. Gut 2002; 50:123–8
Sarasin FP, Majno PE, Llovet JM, et al. Living donor liver transplantation for early hepatocellular carcinoma: a life-expectancy and cost-effectiveness perspective. Hepatology 2001; 33:1073–9
Valentin-Gamazo C, Malago M, Karliova M, et al. Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center. Liver Transpl 2004; 10:1087–96
Lai EC, Fan ST, Lo CM, et al. Hepatic resection for hepatocellular carcinoma. An audit of 343 patients. Ann Surg 1995; 221:291–8
Makuuchi M, Sano K. The surgical approach to HCC: our progress and results in Japan. Liver Transpl 2004; 10:S46–52
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; 243:229–35
Roayaie S, Haim MB, Emre S, et al. Comparison of surgical outcomes for hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: a western experience. Ann Surg Oncol 2000; 7:764–70
Minagawa M, Makuuchi M, Takayama T, et al. Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma. Ann Surg 2003; 238:703–10
Poon RT, Fan ST, Lo CM, et al. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 2002; 235:373–82
Tung-Ping Poon R, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 2000; 232:10–24
Itamoto T, Nakahara H, Tashiro H, et al. Indications of partial hepatectomy for transplantable hepatocellular carcinoma with compensated cirrhosis. Am J Surg 2005; 189:167–72
Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria. Liver Transpl 2002; 8:765–74
Kirimlioglu H, Dvorchick I, Ruppert K, et al. Hepatocellular carcinomas in native livers from patients treated with orthotopic liver transplantation: biologic and therapeutic implications. Hepatology 2001; 34:502–10
Marsh JW, Finkelstein SD, Demetris AJ, et al. Genotyping of hepatocellular carcinoma in liver transplant recipients adds predictive power for determining recurrence-free survival. Liver Transpl 2003; 9:664–71
Acknowledgment
The authors thank Nancy Ehrlich for providing editorial assistance in the preparation of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Facciuto, M.E., Koneru, B., Rocca, J.P. et al. Surgical Treatment of Hepatocellular Carcinoma beyond Milan Criteria. Results of Liver Resection, Salvage Transplantation, and Primary Liver Transplantation. Ann Surg Oncol 15, 1383–1391 (2008). https://doi.org/10.1245/s10434-008-9851-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-008-9851-z