Abstract
Background
Excellent long-term outcomes have been reported recently for patients with small (≤2 cm) hepatocellular carcinoma (HCC). However, the significance of microvascular invasion (MVI) in small HCC remains unclear. The purpose of this study was to determine the impact of MVI in small HCC up to 2 cm.
Methods
In 1,109 patients with solitary HCC from six major international hepatobiliary centers, the impact of MVI on long-term survival in patients with small HCC (≤2 cm) and patients with tumors larger than 2 cm was analyzed.
Results
In patients with small HCC, long-term survival was not affected by MVI (p = 0.8), whereas in patients with larger HCC, significantly worse survival was observed in patients with MVI (p < 0.0001). In multivariate analysis, MVI (hazard ratio [HR] 1.59; 95 % confidence interval (CI) 1.27–1.99; p < 0.001), elevated alpha-fetoprotein (HR 1.41; 95 % CI 1.11–1.8; p = 0.005), and higher histologic grade (HR 1.29; 95 % CI 1.01–1.64; p = 0.04) were significant predictors of worse survival in patients with HCC larger than 2 cm but were not correlated with long-term survival in small HCC. When the cohort was divided into three groups—HCC ≤2, >2 cm without MVI, and HCC >2 cm with MVI—significant between-group survival difference was observed (p < 0.0001).
Conclusions
Small HCC is associated with an excellent prognosis that is not affected by the presence of MVI. The discriminatory power of the 7th edition of the AJCC classification for solitary HCC could be further improved by subdividing tumors according to size (≤2 vs. >2 cm).
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References
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, eds. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.
Cheng CH, Lee CF, Wu TH, Chan KM, Chou HS, Wu TJ, et al. Evaluation of the new AJCC staging system for resectable hepatocellular carcinoma. World J Surg Oncol. 2011;9:114.
Kee KM, Wang JH, Lee CM, Chen CL, Changchien CS, Hu TH, et al. Validation of clinical AJCC/UICC TNM staging system for hepatocellular carcinoma: analysis of 5,613 cases from a medical center in southern Taiwan. Int J Cancer. 2007;120:2650–5.
Lei HJ, Chau GY, Lui WY, Tsay SH, King KL, Loong CC, et al. Prognostic value and clinical relevance of the 6th Edition 2002 American Joint Committee on Cancer staging system in patients with resectable hepatocellular carcinoma. J Am Coll Surg. 2006;203:426–35.
Poon RT, Fan ST. Evaluation of the new AJCC/UICC staging system for hepatocellular carcinoma after hepatic resection in Chinese patients. Surg Oncol Clin N Am. 2003;12:35–50, viii.
Ramacciato G, Mercantini P, Cautero N, Corigliano N, Di Benedetto F, Quintini C, et al. Prognostic evaluation of the new American Joint Committee on Cancer/International Union Against Cancer staging system for hepatocellular carcinoma: analysis of 112 cirrhotic patients resected for hepatocellular carcinoma. Ann Surg Oncol. 2005;12:289–97.
Varotti G, Ramacciato G, Ercolani G, Grazi GL, Vetrone G, Cescon M, et al. Comparison between the fifth and sixth editions of the AJCC/UICC TNM staging systems for hepatocellular carcinoma: multicentric study on 393 cirrhotic resected patients. Eur J Surg Oncol. 2005;31:760–7.
Wu CC, Cheng SB, Ho WM, Chen JT, Liu TJ, P’Eng FK. Liver resection for hepatocellular carcinoma in patients with cirrhosis. Br J Surg. 2005;92:348–55.
Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Yamamoto J, Shimada K, et al. Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology. 1998;28:1241–6.
Yamashita YI, Tsuijita E, Takeishi K, Fujiwara M, Kira S, Mori M, et al. Predictors for microinvasion of small hepatocellular carcinoma ≤ 2 cm. Ann Surg Oncol. 2012;19:2027–34.
Inoue K, Takayama T, Higaki T, Watanabe Y, Makuuchi M. Clinical significance of early hepatocellular carcinoma. Liver Transplant. 2004;10:S16–9.
Todo S, Furukawa H. Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan. Ann Surg. 2004;240:451–9; discussion 59–61.
Livraghi T, Meloni F, Di Stasi M, Rolle E, Solbiati L, Tinelli C, et al. Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice? Hepatology. 2008;47:82–9.
Arii S, Yamaoka Y, Futagawa S, Inoue K, Kobayashi K, Kojiro M, et al. Results of surgical and nonsurgical treatment for small-sized hepatocellular carcinomas: a retrospective and nationwide survey in Japan. The Liver Cancer Study Group of Japan. Hepatology. 2000;32:1224–9.
Liver Cancer Study Group of Japan. The general rules for the clinical and pathological study of primary liver cancer. 5th ed. Tokyo: Kanehara; 2008.
Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–17.
Liver Cancer Study Group of Japan. Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment. Liver Cancer Study Group of Japan. Ann Surg. 1990;211:277–87.
Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–9.
Makuuchi M, Belghiti J, Belli G, Fan ST, Lau JW, Ringe B, et al. IHPBA concordant classification of primary liver cancer: working group report. J Hepatobiliary Pancreatic Surg. 2003;10:26–30.
Jonas S, Bechstein WO, Steinmuller T, Herrmann M, Radke C, Berg T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33:1080–6.
Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462–503.
Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–9.
Rahbari NN, Mehrabi A, Mollberg NM, Muller SA, Koch M, Buchler MW, et al. Hepatocellular carcinoma: current management and perspectives for the future. Ann Surg. 2011;253:453–69.
The Cancer of the Liver Italian Program (CLIP) Investigators. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: The Cancer of the Liver Italian Program (CLIP) Investigators. Hepatology. 1998;28:751–5.
Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19:329–38.
Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol. 2002;20:1527–36.
Vauthey JN, Ribero D, Abdalla EK, Jonas S, Bharat A, Schumacher G, et al. Outcomes of liver transplantation in 490 patients with hepatocellular carcinoma: validation of a uniform staging after surgical treatment. J Am Coll Surg. 2007;204(5):1016–27.
Kanai T, Hirohashi S, Upton MP, Noguchi M, Kishi K, Makuuchi M, et al. Pathology of small hepatocellular carcinoma. A proposal for a new gross classification. Cancer. 1987;60:810–9.
Tsuda H, Zhang WD, Shimosato Y, Yokota J, Terada M, Sugimura T, et al. Allele loss on chromosome 16 associated with progression of human hepatocellular carcinoma. Proc Natl Acad Sci USA. 1990;87:6791–4.
Kojiro M, Yano H, Nakashima O. Pathology of early hepatocellular carcinoma: progression from early to advanced. Semin Surg Oncol. 1996;12:197–203.
Roayaie S, Obeidat K, Sposito C, Mariani L, Bhoori S, Pellegrinelli A, et al. Resection of hepatocellular cancer ≤ 2 cm: results from two western centers. Hepatology. 2012. (accepted).
Sala M, Fuster J, Llovet JM, Navasa M, Sole M, Varela M, et al. High pathological risk of recurrence after surgical resection for hepatocellular carcinoma: an indication for salvage liver transplantation. Liver Transplant. 2004;10:1294–300.
Belghiti J, Cortes A, Abdalla EK, Regimbeau JM, Prakash K, Durand F, et al. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg. 2003;238:885–92; discussion 92–3.
Acknowledgment
The authors thank Ms. Stephanie Deming and Ms. Ruth Haynes for their contribution to our manuscript. The University of Texas MD Anderson Cancer Center is supported in part by the National Institutes of Health through Cancer Center Support Grant CA016672.
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Shindoh, J., Andreou, A., Aloia, T.A. et al. Microvascular Invasion Does Not Predict Long-Term Survival in Hepatocellular Carcinoma up to 2 cm: Reappraisal of the Staging System for Solitary Tumors. Ann Surg Oncol 20, 1223–1229 (2013). https://doi.org/10.1245/s10434-012-2739-y
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DOI: https://doi.org/10.1245/s10434-012-2739-y