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The Impact of Tumor Size on Long-Term Survival Outcomes After Resection of Solitary Hepatocellular Carcinoma: Single-Institution Experience with 2558 Patients

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Journal of Gastrointestinal Surgery Aims and scope



According to the 7th AJCC TNM staging system, solitary hepatocellular carcinoma (HCC) is classified as T1 or T2 based on microvascular invasion (MVI) regardless of tumor size. This study intended to evaluate the prognostic impact of tumor size on survival outcomes after macroscopic curative resection of solitary HCC.


Patients who underwent R0 resection of solitary HCC <10 cm (n = 2558) were selected for study. Follow-up lasted ≥24 months or until death.


HCC was detected during regular health screening or routine follow-up in 2054 cases (80.3 %). Hepatitis B virus (HBV) infection was associated in 2127 (83.2 %). Mean patient age was 54.4 ± 9.9 years. Anatomical resection was performed in 1786 (69.8 %). MVI was identified in 407 (16.0 %) which therefore became stage T2; the other 2150 became stage T1. Tumor recurrence and patient survival rates were 24.9 and 95.0 % after 1 year, 49.6 and 84.1 % after 3 years, 57.7 and 75.0 % after 5 years, and 67.3 and 56.6 % after 10 years, respectively. Multivariate analysis showed that non-anatomical resection, MVI, and tumor size >5 cm were independent risk factors for both tumor recurrence and overall patient survival. Long-term survival correlated negatively with tumor size and MVI. Subgroup analysis with MVI and size cutoff of 5 cm revealed a significant survival difference (p = 0.000). Tumor size >5 cm was not a significant prognostic factor in non-HBV patients.


These results suggest that the prognostic impact of tumor size may be underestimated in the current version of the AJCC staging system and that solitary HCC staging could be improved with inclusion of tumor size cutoff of 5 cm in HBV-associated patients. Further validation is necessary with multicenter studies.

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  1. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet 2012; 379:1245–1255.

    Article  PubMed  Google Scholar 

  2. El-Serag HB. Hepatocellular carcinoma. N Engl J Med 2011; 365:1118–1127.

    Article  CAS  PubMed  Google Scholar 

  3. Song TJ, Ip EW, Fong Y. Hepatocellular carcinoma: current surgical management. Gastroenterology 2004; 127:S248–260.

    Article  PubMed  Google Scholar 

  4. Lee SG, Hwang S, Jung JP, Lee YJ, Kim KH, Ahn CS. Outcome of patients with huge hepatocellular carcinoma after primary resection and treatment of recurrent lesions. Br J Surg 2007; 94:320–326

    Article  CAS  PubMed  Google Scholar 

  5. Pawlik TM, Delman KA, Vauthey JN, Nagorney DM, Ng IO, Ikai I, et al. Tumor size predicts vascular invasion and histologic grade: implications for selection of surgical treatment for hepatocellular carcinoma. Liver Transpl 2005; 11:1086–1092.

    Article  PubMed  Google Scholar 

  6. Tandon P, Garcia-Tsao G. Prognostic indicators in hepatocellular carcinoma: a systematic review of 72 studies. Liver Int 2009; 29:502–510.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, et al. Simplified staging for hepatocellular carcinoma. J Clin Oncol 2002; 20:1527–1536.

    Article  PubMed  Google Scholar 

  8. Zhang H, Yuan SX, Dai SY, Zhang JM, Huang X, Lu CD, et al. Tumor size does not independently affect long-term survival after curative resection of solitary hepatocellular carcinoma without macroscopic vascular invasion. World J Surg 2014; 38:947–957.

    Article  PubMed  Google Scholar 

  9. Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999; 19:329–338.

    Article  CAS  PubMed  Google Scholar 

  10. Kudo M, Chung H, Osaki Y. Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score). J Gastroenterol 2003; 38:207–215.

    Article  PubMed  Google Scholar 

  11. Kudo M, Chung H, Haji S, Osaki Y, Oka H, Seki T, et al. Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score. Hepatology 2004; 40:1396–1405.

    Article  PubMed  Google Scholar 

  12. Yau T, Tang VY, Yao TJ, Fan ST, Lo CM, Poon RT. Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology 2014; 146:1691–1700.

    Article  PubMed  Google Scholar 

  13. Korean Association for the Study of the Liver. KASL Clinical Practice Guidelines: Management of chronic hepatitis B. Clin Mol Hepatol 2012;18:109-162.

  14. Song do S, Bae SH. Changes of guidelines diagnosing hepatocellular carcinoma during the last ten-year period. Clin Mol Hepatol 2012;18:258–267.

  15. Suk KT, Baik SK, Yoon JH, Cheong JY, Paik YH, Lee CH, et al; Korean Association for the Study of the Liver. Revision and update on clinical practice guideline for liver cirrhosis. Korean J Hepatol 2012;18:1–21.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Zhou Y, Zhang Z, Zhao Y, Wu L, Li B. Antiviral therapy decreases recurrence of hepatitis B virus-related hepatocellular carcinoma after curative resection: a meta-analysis. World J Surg 2014; 38:2395–2402.

    Article  PubMed  Google Scholar 

  17. Hwang S, Lee SG, Moon DB, Ahn CS, Kim KH, Lee YJ, et al. Salvage living donor liver transplantation after prior liver resection for hepatocellular carcinoma. Liver Transpl 2007; 13:741–746.

    Article  PubMed  Google Scholar 

  18. Choi GH, Shim JH, Kim MJ, Ryu MH, Ryoo BY, Kang YK, et al. Sorafenib alone versus sorafenib combined with transarterial chemoembolization for advanced-stage hepatocellular carcinoma: results of propensity score analyses. Radiology 2013; 269:603–611.

    Article  PubMed  Google Scholar 

  19. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, III, eds. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.

    Google Scholar 

  20. Ariizumi S, Kotera Y, Takahashi Y, Katagiri S, Yamamoto M. Impact of hepatectomy for huge solitary hepatocellular carcinoma. J Surg Oncol 2013; 107:408–413.

    Article  PubMed  Google Scholar 

  21. Yang LY, Fang F, Ou DP, Wu W, Zeng ZJ, Wu F. Solitary large hepatocellular carcinoma: a specific subtype of hepatocellular carcinoma with good outcome after hepatic resection. Ann Surg 2009; 249:118–123.

    Article  PubMed  Google Scholar 

  22. Bruix J, Sherman M. Management of hepatocellular carcinoma: An update. Hepatology 2011; 53: 1020–1022.

  23. Shindoh J, Andreou A, Aloia TA, Zimmitti G, Lauwers GY, Laurent 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 2013;20:1223–1229.

    Article  PubMed  Google Scholar 

  24. Okamura Y, Ito T, Sugiura T, Mori K, Uesaka K. Anatomic versus nonanatomic hepatectomy for a solitary hepatocellular carcinoma: a case-controlled study with propensity score matching. J Gastrointest Surg 2014; 18:1994–2002.

    Article  PubMed  Google Scholar 

  25. Tomimaru Y, Eguchi H, Marubashi S, Wada H, Kobayashi S, Tanemura M, et al. Equivalent outcomes after anatomical and non-anatomical resection of small hepatocellular carcinoma in patients with preserved liver function. Dig Dis Sci 2012; 57:1942–1948.

    Article  PubMed  Google Scholar 

  26. Yamazaki O, Matsuyama M, Horii K, Kanazawa A, Shimizu S, Uenishi T, et al. Comparison of the outcomes between anatomical resection and limited resection for single hepatocellular carcinomas no larger than 5 cm in diameter: a single-center study. J Hepatobiliary Pancreat Sci 2010; 17:349–358.

    Article  PubMed  Google Scholar 

  27. Shindoh J, Hasegawa K, Inoue Y, Ishizawa T, Nagata R, Aoki T, et al. Risk factors of post-operative recurrence and adequate surgical approach to improve long-term outcomes of hepatocellular carcinoma. HPB (Oxford) 2013;15:31–39.

    Article  Google Scholar 

  28. 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 2013;57:1426–1435.

  29. Ahn SG, Kim SH, Jeon TJ, Cho HJ, Choi SB, Yun MJ, et al. The role of preoperative [18F]fluorodeoxyglucose positron emission tomography in predicting early recurrence after curative resection of hepatocellular carcinomas. J Gastrointest Surg 2011; 15:2044–2052.

    Article  PubMed  Google Scholar 

  30. Kitamura K, Hatano E, Higashi T, Seo S, Nakamoto Y, Yamanaka K, et al. Preoperative FDG-PET predicts recurrence patterns in hepatocellular carcinoma. Ann Surg Oncol 2012; 19:156–162.

    Article  PubMed  Google Scholar 

  31. Roayaie S, Blume IN, Thung SN, Guido M, Fiel MI, Hiotis S, et al. A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology 2009;137: 850–855.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Torzilli G, Belghiti J, Kokudo N, Takayama T, Capussotti L, Nuzzo G, et al. A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations?: an observational study of the HCC East-West study group. Ann Surg 2013;257:929–937.

    Article  PubMed  Google Scholar 

  33. Kluger MD, Salceda JA, Laurent A, Tayar C, Duvoux C, Decaens T, et al. Liver resection for hepatocellular carcinoma in 313 Western patients: tumor biology and underlying liver rather than tumor size drive prognosis. J Hepatol 2014

  34. Hiwatashi K, Ueno S, Sakoda M, Iino S, Minami K, Yamasaki Y, et al. Problems of long survival following surgery in patients with nonBnonC-HCC: comparison with HBV and HCV related-HCC. J Cancer 2015;6:438–447.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Shrager B, Jibara G, Schwartz M, Roayaie S. Resection of hepatocellular car cinoma without cirrhosis. Ann Surg 2012;255:1135–1143.

    Article  PubMed  Google Scholar 

  36. Young AL, Adair R, Prasad KR, Toogood GJ, Lodge JP. Hepatocellular carcinoma within a noncirrhotic, nonfibrotic, seronegative liver: surgical approaches and outcomes. J Am Coll Surg 2012;214:174–183.

    Article  PubMed  Google Scholar 

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Conflict of Interest

None of the authors has any conflict of interest.

Source of Funding

None of the authors was supported financially for this study.

Author Contribution

Hwang S, Lee YJ, and Lee SG designed the study; Kim KH, Ahn CS, Moon DB, Ha TY, Jung DH, and Song GW contributed to the acquisition and analysis of data; and Hwang S drafted and revised the article.

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Correspondence to Shin Hwang.

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Hwang, S., Lee, YJ., Kim, KH. et al. The Impact of Tumor Size on Long-Term Survival Outcomes After Resection of Solitary Hepatocellular Carcinoma: Single-Institution Experience with 2558 Patients. J Gastrointest Surg 19, 1281–1290 (2015).

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