Review

Resection and transplantation for hepatocellular carcinoma: factors influencing surgical options

Johns Hopkins University School of Medicine, Department of Surgery, 600 North Wolfe Street, Blalock 688, Baltimore, MD 21287, USA

Search for more papers by this author

Jin He

Johns Hopkins University School of Medicine, Department of Surgery, 600 North Wolfe Street, Blalock 688, Baltimore, MD 21287, USA

Search for more papers by this author

Timothy M Pawlik

* Author for correspondence:

E-mail Address: tpawlik1@jhmi.edu

Johns Hopkins University School of Medicine, Department of Surgery, 600 North Wolfe Street, Blalock 688, Baltimore, MD 21287, USA

Search for more papers by this author

Published Online:23 Apr 2014https://doi.org/10.2217/fon.13.225

View article

Abstract

ABSTRACT:

The management of hepatocellular carcinoma within the Milan criteria and with well-compensated cirrhosis is a topic of debate. Recent surveillance programs in patients with hepatitis C and cirrhosis have allowed some patients to be diagnosed with early, potentially curable, disease via liver resection (LR), liver transplantation (LT) or liver ablation. LT has excellent outcomes with 5–year survival rates >70% for patients within the Milan criteria. However, its utilization is limited by increasing organ shortages. LR is also effective with 5–year survival outcomes between 50–70% and safe in light of advances in surgical technique, preresection optimization and patient selection. Patients with solitary tumors and well-preserved liver function are good candidates for LR, whereas LT is best reserved for patients with compromised liver function and multifocal disease. LT and LR should not be viewed as competing tools but as complementary tools in the current armamentarium to treat early hepatocellular carcinoma.

Keywords:

Papers of special note have highlighted as:

•of interest

References

1 El-Serag HB. Hepatocellular carcinoma. N. Engl. J. Med. 365(12), 1118–1127 (2011).Crossref, Medline, CAS, Google Scholar
2 Altekruse SF, Mcglynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J. Clin. Oncol. 27(9), 1485–1491 (2009).Crossref, Medline, Google Scholar
3 Utsunomiya T, Shimada M, Kudo M et al. Nationwide study of 4741 patients with non-B non-C hepatocellular carcinoma with special reference to the therapeutic impact. Ann. Surg. 259(2), 336–345 (2013).Crossref, Google Scholar
4 Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet 379(9822), 1245–1255 (2012).• Review of the overall treatment of hepatocellular carcinoma (HCC) and highlights the Barcenola Clinic Liver Cancer staging and treatment strategy.Crossref, Medline, Google Scholar
5 Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359(4), 378–390 (2008).Crossref, Medline, CAS, Google Scholar
6 Cheng AL, Kang YK, Chen Z et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a Phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10(1), 25–34 (2009).Crossref, Medline, CAS, Google Scholar
7 Samuel M, Chow PK, Chan Shih-Yen E, Machin D, Soo KC. Neoadjuvant and adjuvant therapy for surgical resection of hepatocellular carcinoma. Cochrane Database Syst. Rev. 1, CD001199 (2009).Medline, Google Scholar
8 Lau WY, Lai EC, Lau SH. The current role of neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for hepatocellular carcinoma: a systematic review. Hepatobiliary Pancreat. Dis. Int. 8(2), 124–133 (2009).Medline, CAS, Google Scholar
9 Toso C, Mentha G, Kneteman NM, Majno P. The place of downstaging for hepatocellular carcinoma. J. Hepatol. 52(6), 930–936 (2010).Crossref, Medline, Google Scholar
10 Villanueva A, Llovet JM. Targeted therapies for hepatocellular carcinoma. Gastroenterology 140(5), 1410–1426 (2011).Crossref, Medline, CAS, Google Scholar
11 Yoo EJ, Shin HS, Kim SU et al. Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma. Onco. Targets Ther. 6, 755–759 (2013).Crossref, Medline, CAS, Google Scholar
12 Vagefi PA, Hirose R. Downstaging of hepatocellular carcinoma prior to liver transplant: is there a role for adjuvant sorafenib in locoregional therapy? J. Gastrointest. Cancer 41(4), 217–220 (2010).Crossref, Medline, Google Scholar
13 Barbier L, Muscari F, Le Guellec S, Pariente A, Otal P, Suc B. Liver resection after downstaging hepatocellular carcinoma with sorafenib. Int. J. Hepatol. 791013 (2011).Medline, Google Scholar
14 Pawlik TM, Poon RT, Abdalla EK et al. Critical appraisal of the clinical and pathologic predictors of survival after resection of large hepatocellular carcinoma. Arch Surg. 140(5), 450–457; discussion 457–458 (2005).Crossref, Medline, Google Scholar
15 Garrison RN, Cryer HM, Howard DA, Polk HC Jr. Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis. Ann. Surg. 199(6), 648–655 (1984).Crossref, Medline, CAS, Google Scholar
16 Mansour A, Watson W, Shayani V, Pickleman J. Abdominal operations in patients with cirrhosis: still a major surgical challenge. Surgery 122(4), 730–735; discussion 735–736 (1997).Crossref, Medline, CAS, Google Scholar
17 Bruix J, Castells A, Bosch J et al. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology 111(4), 1018–1022 (1996).Crossref, Medline, CAS, Google Scholar
18 Teh SH, Christein J, Donohue J et al. Hepatic resection of hepatocellular carcinoma in patients with cirrhosis: Model of End-Stage Liver Disease (MELD) score predicts perioperative mortality. J. Gastrointest. Surg. 9(9), 1207–1215; discussion 1215 (2005).Crossref, Medline, Google Scholar
19 Teh SH, Nagorney DM, Stevens SR et al. Risk factors for mortality after surgery in patients with cirrhosis. Gastroenterology 132(4), 1261–1269 (2007).Crossref, Medline, Google Scholar
20 Cucchetti A, Ercolani G, Vivarelli M et al. Impact of model for end-stage liver disease (MELD) score on prognosis after hepatectomy for hepatocellular carcinoma on cirrhosis. Liver Transplant. 12(6), 966–971 (2006).Crossref, Medline, Google Scholar
21 Ripoll C, Groszmann R, Garcia-Tsao G et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology 133(2), 481–488 (2007).• Hepatic venous pressure gradient <10 mmHg had a 90% probability of not developing clinical decompensation – highlights importance of preoperative evaluation.Crossref, Medline, CAS, Google Scholar
22 Boleslawski E, Petrovai G, Truant S et al. Hepatic venous pressure gradient in the assessment of portal hypertension before liver resection in patients with cirrhosis. Br. J. Surg. 99(6), 855–863 (2012).Crossref, Medline, CAS, Google Scholar
23 Vauthey JN, Lauwers GY, Esnaola NF et al. Simplified staging for hepatocellular carcinoma. J. Clin. Oncol. 20(6), 1527–1536 (2002).Crossref, Medline, Google Scholar
24 Vauthey JN, Dixon E, Abdalla EK et al. Pretreatment assessment of hepatocellular carcinoma: expert consensus statement. HPB 12(5), 289–299 (2010).Crossref, Medline, Google Scholar
25 Farges O, Belghiti J, Kianmanesh R et al. Portal vein embolization before right hepatectomy: prospective clinical trial. Ann. Surg. 237(2), 208–217 (2003).Crossref, Medline, Google Scholar
26 Palavecino M, Chun YS, Madoff DC et al. Major hepatic resection for hepatocellular carcinoma with or without portal vein embolization: perioperative outcome and survival. Surgery 145(4), 399–405 (2009).• Portal vein embolization is safe and decreases perioperative mortality.Crossref, Medline, Google Scholar
27 Abulkhir A, Limongelli P, Healey AJ et al. Preoperative portal vein embolization for major liver resection: a meta-analysis. Ann. Surg. 247(1), 49–57 (2008).Crossref, Medline, Google Scholar
28 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 Transplant. 11(9), 1086–1092 (2005).Crossref, Medline, Google Scholar
29 Truant S, Boleslawski E, Duhamel A et al. Tumor size of hepatocellular carcinoma in noncirrhotic liver: a controversial predictive factor for outcome after resection. Eur. J. Surg. Oncol. 38(12), 1189–1196 (2012).Crossref, Medline, CAS, Google Scholar
30 Liau KH, Ruo L, Shia J et al. Outcome of partial hepatectomy for large (> 10 cm) hepatocellular carcinoma. Cancer 104(9), 1948–1955 (2005).Crossref, Medline, Google Scholar
31 Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin. Liver Dis. 19(3), 329–338 (1999).Crossref, Medline, CAS, Google Scholar
32 Primary liver cancer in Japan.Clinicopathologic features and results of surgical treatment. Liver Cancer Study Group of Japan. Ann. Surg. 211(3), 277–287 (1990).Medline, Google Scholar
33 Ikai I, Yamamoto Y, Yamamoto N et al. Results of hepatic resection for hepatocellular carcinoma invading major portal and/or hepatic veins. Surg. Oncol. Clin. North Am. 12(1), 65–75, ix (2003).Crossref, Medline, Google Scholar
34 Roayaie S, Jibara G, Taouli B, Schwartz M. Resection of hepatocellular carcinoma with macroscopic vascular invasion. Ann. Surg. Oncol. 20(12), 3754–3760 (2013).Crossref, Medline, Google Scholar
35 Izumi R, Shimizu K, Ii T et al. Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection. Gastroenterology 106(3), 720–727 (1994).Crossref, Medline, CAS, Google Scholar
36 Roayaie S, Blume IN, Thung SN et al. A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology 137(3), 850–855 (2009).Crossref, Medline, Google Scholar
37 Cillo U, Vitale A, Bassanello M et al. Liver transplantation for the treatment of moderately or well-differentiated hepatocellular carcinoma. Ann. Surg. 239(2), 150–159 (2004).Crossref, Medline, Google Scholar
38 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 33(6), 1394–1403 (2001).Crossref, Medline, CAS, Google Scholar
39 Wang BW, Mok KT, Liu SI et al. Is hepatectomy beneficial in the treatment of multinodular hepatocellular carcinoma? J. Formos. Med. Assoc. 107(8), 616–626 (2008).Crossref, Medline, Google Scholar
40 Ishizawa T, Hasegawa K, Aoki T et al. Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 134(7), 1908–1916 (2008).Crossref, Medline, Google Scholar
41 Bismuth H, Chiche L, Adam R, Castaing D. Surgical treatment of hepatocellular carcinoma in cirrhosis: liver resection or transplantation? Transplant. Proc. 25(1 Pt 2), 1066–1067 (1993).Medline, CAS, Google Scholar
42 Ma WJ, Wang HY, Teng LS. Correlation analysis of preoperative serum alpha-fetoprotein (AFP) level and prognosis of hepatocellular carcinoma (HCC) after hepatectomy. World J. Surg. Oncol. 11(1), 212 (2013).Crossref, Medline, Google Scholar
43 Santambrogio R, Opocher E, Costa M et al. Hepatic resection for ‘BCLC stage A’ hepatocellular carcinoma. The prognostic role of alpha-fetoprotein. Ann. Surg. Oncol. 19(2), 426–434 (2012).Crossref, Medline, Google Scholar
44 Tyson GL, Duan Z, Kramer JR, Davila JA, Richardson PA, El-Serag HB. Level of alpha-fetoprotein predicts mortality among patients with hepatitis C-related hepatocellular carcinoma. Clin. Gastroenterol. Hepatol. 9(11), 989–994 (2011).Crossref, Medline, CAS, Google Scholar
45 Shim JH, Yoon DL, Han S et al. Is serum alpha-fetoprotein useful for predicting recurrence and mortality specific to hepatocellular carcinoma after hepatectomy? A test based on propensity scores and competing risks analysis. Ann. Surg. Oncol. 19(12), 3687–3696 (2012).Crossref, Medline, Google Scholar
46 Nanashima A, Taura N, Abo T et al. Tumor marker levels before and after curative treatment of hepatocellular carcinoma as predictors of patient survival. Dig. Dis. Sci. 56(10), 3086–3100 (2011).Crossref, Medline, CAS, Google Scholar
47 Duvoux C, Roudot-Thoraval F, Decaens T et al. Liver transplantation for hepatocellular carcinoma: a model including alpha-fetoprotein improves the performance of Milan criteria. Gastroenterology 143(4), 986–994 e983; quiz e914–e985 (2012).Crossref, Medline, CAS, Google Scholar
48 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. 334(11), 693–699 (1996).Crossref, Medline, CAS, Google Scholar
49 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. 21(23), 4329–4335 (2003).Crossref, Medline, Google Scholar
50 Bellavance EC, Lumpkins KM, Mentha G et al. Surgical management of early-stage hepatocellular carcinoma: resection or transplantation? J. Gastrointest. Surg. 12(10), 1699–1708 (2008).• Supports initial resection for early-stage HCC with Model for End-Stage Liver Disease ≤8 and without evidence of hepatitis given transplantation confers more pronounced disease-free survival in patients with hepatitis C virus and attenuated in overall survival in patients with Model for End-Stage Liver Disease ≤8.Crossref, Medline, Google Scholar
51 Wong LL. Current status of liver transplantation for hepatocellular cancer. Am. J. Surg. 183(3), 309–316 (2002).Crossref, Medline, Google Scholar
52 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.. Hepatology31(4), 899–906 (2000).Crossref, Medline, CAS, Google Scholar
53 Sarasin FP, Giostra E, Mentha G, Hadengue A. Partial hepatectomy or orthotopic liver transplantation for the treatment of resectable hepatocellular carcinoma? A cost–effectiveness perspective. Hepatology 28(2), 436–442 (1998).Crossref, Medline, CAS, Google Scholar
54 Poon RT, Fan ST, Lo CM, Liu CL, Wong J. 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. 235(3), 373–382 (2002).Crossref, Medline, Google Scholar
55 Fuks D, Dokmak S, Paradis V, Diouf M, Durand F, Belghiti J. Benefit of initial resection of hepatocellular carcinoma followed by transplantation in case of recurrence: an intention-to-treat analysis. Hepatology 55(1), 132–140 (2012).Crossref, Medline, Google Scholar
56 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 Transplant. 10(10), 1294–1300 (2004).Crossref, Medline, Google Scholar
57 Margarit C, Escartin A, Castells L, Vargas V, Allende E, Bilbao I. Resection for hepatocellular carcinoma is a good option in Child-Turcotte-Pugh class A patients with cirrhosis who are eligible for liver transplantation. Liver Transplant. 11(10), 1242–1251 (2005).Crossref, Medline, Google Scholar
58 Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30(6), 1434–1440 (1999).Crossref, Medline, CAS, Google Scholar
59 Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Semin. Liver Dis. 25(2), 181–200 (2005).Crossref, Medline, Google Scholar
60 Kim WR, Stock PG, Smith JM et al. OPTN/SRTR 2011 Annual Data Report: liver. Am. J. Transplant. 13(Suppl 1), 73–102 (2013).Crossref, Medline, Google Scholar
61 Bhangui P, Vibert E, Majno P et al. Intention-to-treat analysis of liver transplantation for hepatocellular carcinoma: living versus deceased donor transplantation. Hepatology 53(5), 1570–1579 (2011).Crossref, Medline, Google Scholar
62 Freeman RB Jr, Wiesner RH, Harper A et al. The new liver allocation system: moving toward evidence-based transplantation policy. Liver Transplant. 8(9), 851–858 (2002).Crossref, Medline, Google Scholar
63 Massie AB, Caffo B, Gentry SE et al. MELD exceptions and rates of waiting list outcomes. Am. J. Transplant. 11(11), 2362–2371 (2011).Crossref, Medline, CAS, Google Scholar
64 Berry K, Ioannou GN. Are patients with Child’s A cirrhosis and hepatocellular carcinoma appropriate candidates for liver transplantation? Am. J. Transplant. 12(3), 706–717 (2012).Crossref, Medline, CAS, Google Scholar
65 Nathan H, Hyder O, Mayo SC et al. Surgical therapy for early hepatocellular carcinoma in the modern era: a 10-year SEER-medicare analysis. Ann. Surg. 258(6), 1022–1027 (2013).• Uses population-based data to determine current surgical practices for HCC in the USA and demonstrate a barrier to surgical therapy.Crossref, Medline, Google Scholar
66 Nathan H, Bridges JF, Schulick RD et al. Understanding surgical decision making in early hepatocellular carcinoma. J. Clin. Oncol. 29(6), 619–625 (2011).Crossref, Medline, Google Scholar
67 Nathan H, Segev DL, Bridges JF et al. Influence of nonclinical factors on choice of therapy for early hepatocellular carcinoma. Ann. Surg. Oncol. 20(2), 448–456 (2013).Crossref, Medline, Google Scholar
68 Wee A. Fine-needle aspiration biopsy of hepatocellular carcinoma and related hepatocellular nodular lesions in cirrhosis: controversies, challenges, and expectations. Pathol. Res. Int. 2011, 587936 (2011).Medline, Google Scholar
69 Woo HG, Park ES, Thorgeirsson SS, Kim YJ. Exploring genomic profiles of hepatocellular carcinoma. Mol. Carcinogen. 50(4), 235–243 (2011).Crossref, Medline, CAS, Google Scholar
70 Villanueva A, Hoshida Y, Battiston C et al. Combining clinical, pathology, and gene expression data to predict recurrence of hepatocellular carcinoma. Gastroenterol. 140(5), 1501.e2–1512.e2 (2011).Crossref, Google Scholar

Vol. 10, No. 4

Metrics

Downloaded 110 times

History

Published online 23 April 2014

Published in print March 2014

Information

Keywords

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

PDF download