Endoscopic hepatic resection and endoscopic radiofrequency ablation as initial treatments for hepatocellular carcinoma within the Milan criteria

  • Masayo Tsukamoto
  • Katsunori ImaiEmail author
  • Yo-ichi Yamashita
  • Yuki Kitano
  • Hirohisa Okabe
  • Shigeki Nakagawa
  • Hidetoshi Nitta
  • Akira Chikamoto
  • Takatoshi Ishiko
  • Hideo Baba
Original Article



The indication of endoscopic (laparoscopic and thoracoscopic) hepatic resection (HR) has been expanded in the past decade because of its low invasiveness. However, the indications of endoscopic HR and radiofrequency ablation (RFA) have not yet been determined.


Among the 906 patients hospitalized for the initial treatment of hepatocellular carcinoma (HCC) between 2000 and 2017, 77 underwent endoscopic partial HR (E-pHR), and 94 underwent endoscopic RFA (E-RFA). We compared the short- and long-term outcomes between the E-pHR and E-RFA groups.


The patients in the E-RFA group were characterized primarily by an impaired liver function. Among the patients with liver damage B or C, the overall survival (OS) in the E-pHR group was significantly worse than in the E-RFA group (3-year OS: 36% vs. 82%, p = 0.003).


E-RFA may be recommended for the initial treatment of HCC in patients with a severely impaired liver function. However, E-pHR should be avoided as the initial treatment of HCC in such patients.


Endoscopic surgery Hepatic resection Radiofrequency ablation Hepatocellular carcinoma Milan criteria 


Compliance with ethical standards

Conflicts of interest

Masayo Tsukamoto and co-authors declare that we have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

595_2019_1903_MOESM1_ESM.tif (82 kb)
Supplementary file 1 (83 kb)


  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–E386386.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Chen MS, Li JQ, Zheng Y, Guo RP, Liang HH, Zhang YQ, et al. A prospective randomized trial comparing percutaneous local ablative therapy and partial hepatectomy for small hepatocellular carcinoma. Ann Surg. 2006;243:321–8.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Hasegawa K, Makuuchi M, Takayama T, Kokudo N, Arii S, Okazaki M, et al. Surgical resection vs. percutaneous ablation for hepatocellular carcinoma: a preliminary report of the Japanese nationwide survey. J Hepatol. 2008;49:589–94.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, 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. 2009;10:25–34.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Meng MB, Cui YL, Lu Y, She B, Chen Y, Guan YS, et al. Transcatheter arterial chemoembolization in combination with radiotherapy for unresectable hepatocellular carcinoma: a systematic review and meta-analysis. Radiother Oncol. 2009;92:184–94.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Imai K, Beppu T, Chikamoto A, Mima K, Okabe H, Hayashi H, et al. Salvage treatment for local recurrence of hepatocellular carcinoma after local ablation therapy. Hepatol Res. 2014;44:E335–E34545.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Wang C, Wang H, Yang W, Hu K, Xie H, Hu KQ, et al. Multicenter randomized controlled trial of percutaneous cryoablation versus radiofrequency ablation in hepatocellular carcinoma. Hepatology (Baltimore, MD). 2015;61:1579–90.CrossRefGoogle Scholar
  9. 9.
    Reich H, McGlynn F, DeCaprio J, Budin R. Laparoscopic excision of benign liver lesions. Obstet Gynecol. 1991;78:956–8.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Buell JF, Cherqui D, Geller DA, O'Rourke N, Iannitti D, Dagher I, et al. The international position on laparoscopic liver surgery: the Louisville Statement, 2008. Ann Surg. 2009;250:825–30.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Wakabayashi G. What has changed after the Morioka consensus conference 2014 on laparoscopic liver resection? Hepatobiliary Surg Nutr. 2016;5:281–9.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Cho JY, Han HS, Wakabayashi G, Soubrane O, Geller D, O'Rourke N, et al. Practical guidelines for performing laparoscopic liver resection based on the second international laparoscopic liver consensus conference. Surg Oncol. 2018;27:A5–9.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology (Baltimore, MD). 2011;53:1020–2.CrossRefGoogle Scholar
  14. 14.
    Duan C, Liu M, Zhang Z, Ma K, Bie P. Radiofrequency ablation versus hepatic resection for the treatment of early-stage hepatocellular carcinoma meeting Milan criteria: a systematic review and meta-analysis. World J Surg Oncol. 2013;11:190.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology (Baltimore, MD). 2005;42:1208–36.CrossRefGoogle Scholar
  16. 16.
    Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, 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;35:421–30.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Makuuchi M, Kokudo N, Arii S, Futagawa S, Kaneko S, Kawasaki S, et al. Development of evidence-based clinical guidelines for the diagnosis and treatment of hepatocellular carcinoma in Japan. Hepatol Res. 2008;38:37–51.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Imai K, Beppu T, Chikamoto A, Doni K, Okabe H, Hayashi H, et al. Comparison between hepatic resection and radiofrequency ablation as first-line treatment for solitary small-sized hepatocellular carcinoma of 3 cm or less. Hepatol Res. 2013;43:853–64.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Liu JG, Wang YJ, Du Z. Radiofrequency ablation in the treatment of small hepatocellular carcinoma: a meta analysis. World J Gastroenterol. 2010;16:3450–6.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Nitta H, Nakagawa S, Kaida T, Arima K, Higashi T, Taki K, et al. Pre-treatment double- or triple-positive tumor markers are predictive of a poor outcome for patients undergoing radiofrequency ablation for hepatocellular carcinoma. Surg Today. 2017;47:375–84.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Zhou Y, Zhao Y, Li B, Xu D, Yin Z, Xie F, et al. Meta-analysis of radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma. BMC Gastroenterol. 2010;10:78.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Ito T, Tanaka S, Iwai S, Takemura S, Hagihara A, Uchida-Kobayashi S, et al. Outcomes of laparoscopic hepatic resection versus percutaneous radiofrequency ablation for hepatocellular carcinoma located at the liver surface: a case-control study with propensity score matching. Hepatol Res. 2016;46:565–74.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Lai EC, Tang CN. Radiofrequency ablation versus hepatic resection for hepatocellular carcinoma within the Milan criteria—a comparative study. Int J Surg. 2013;11:77–80.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Feng K, Yan J, Li X, Xia F, Ma K, Wang S, et al. A randomized controlled trial of radiofrequency ablation and surgical resection in the treatment of small hepatocellular carcinoma. J Hepatol. 2012;57:794–802.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Ueno S, Sakoda M, Kubo F, Hiwatashi K, Tateno T, Baba Y, et al. Surgical resection versus radiofrequency ablation for small hepatocellular carcinomas within the Milan criteria. J Hepatobiliary Pancreat Surg. 2009;16:359–66.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Hasegawa K, Kokudo N, Makuuchi M, Izumi N, Ichida T, Kudo M, et al. Comparison of resection and ablation for hepatocellular carcinoma: a cohort study based on a Japanese nationwide survey. J Hepatol. 2013;58:724–9.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Martin RC 2nd, Mbah NA, St Hill R, Kooby D, Weber S, Scoggins CR, et al. Laparoscopic versus open hepatic resection for hepatocellular carcinoma: improvement in outcomes and similar cost. World J Surg. 2015;39:1519–26.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Takahara T, Wakabayashi G, Beppu T, Aihara A, Hasegawa K, Gotohda N, et al. Long-term and perioperative outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma with propensity score matching: a multi-institutional Japanese study. J Hepatobiliary Pancreat Sci. 2015;22:721–7.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Franken C, Lau B, Putchakayala K, DiFronzo LA. Comparison of short-term outcomes in laparoscopic vs open hepatectomy. JAMA Surg. 2014;149:941–6.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Jiang B, Yan X, Zhang JH. Meta-analysis of laparoscopic versus open liver resection for hepatocellular carcinoma. Hepatol Res. 2018;48:635–63.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Santambrogio R, Barabino M, Bruno S, Mariani N, Maroni N, Bertolini E, et al. Surgical resection vs. ablative therapies through a laparoscopic approach for hepatocellular carcinoma: a comparative study. J Gastrointest Surg. 2017;22:650–60.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Yazici P, Akyuz M, Yigitbas H, Dural C, Okoh A, Aydin N, et al. A comparison of perioperative outcomes in elderly patients with malignant liver tumors undergoing laparoscopic liver resection versus radiofrequency ablation. Surg Endosc. 2017;31:1269–74.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Ikai I, Takayasu K, Omata M, Okita K, Nakanuma Y, Matsuyama Y, et al. A modified Japan Integrated Stage score for prognostic assessment in patients with hepatocellular carcinoma. J Gastroenterol. 2006;41:884–92.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Nanashima A, Sumida Y, Abo T, Shindou H, Fukuoka H, Takeshita H, et al. Modified Japan Integrated Staging is currently the best available staging system for hepatocellular carcinoma patients who have undergone hepatectomy. J Gastroenterol. 2006;41:250–6.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Ban D, Tanabe M, Ito H, Otsuka Y, Nitta H, Abe Y, et al. A novel difficulty scoring system for laparoscopic liver resection. J Hepatobiliary Pancreat Sci. 2014;21:745–53.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Yamao T, Imai K, Yamashita YI, Umezaki N, Tsukamoto M, Kitano Y, et al. Thoracoscopic surgery for hepatocellular carcinoma located in the hepatic dome: technical aspect and oncological results. Asian J Endosc Surg. 2019. Scholar
  37. 37.
    Doni K, Beppu T, Ishiko T, Chikamoto A, Hayashi H, Imai K, et al. Endoscopic radiofrequency ablation in elderly patients with hepatocellular carcinoma. Anticancer Res. 2015;35:3033–40.Google Scholar
  38. 38.
    Imai K, Beppu T, Nakayama Y, Ishiko T, Horino K, Komori H, et al. Preoperative prediction of poorly differentiated components in small-sized hepatocellular carcinoma for safe local ablation therapy. J Surg Oncol. 2009;100:121–6.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Utsunomiya T, Shimada M, Kudo M, Ichida T, Matsui O, Izumi N, et al. Nationwide study of 4741 patients with non-B non-C hepatocellular carcinoma with special reference to the therapeutic impact. Ann Surg. 2014;259:336–45.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    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 (Baltimore, MD). 2004;40:1396–405.CrossRefGoogle Scholar
  42. 42.
    Yamao T, Imai K, Yamashita YI, Kaida T, Nakagawa S, Mima K, et al. Surgical treatment strategy for hepatocellular carcinoma in patients with impaired liver function: hepatic resection or radiofrequency ablation? HPB Off J Int Hepatol Pancreat Biliary Assoc. 2018;20:244–50.CrossRefGoogle Scholar
  43. 43.
    Hori T, Nagata K, Hasuike S, Onaga M, Motoda M, Moriuchi A, et al. Risk factors for the local recurrence of hepatocellular carcinoma after a single session of percutaneous radiofrequency ablation. J Gastroenterol. 2003;38:977–81.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Park W, Chung YH, Kim JA, Jin YJ, Lee D, Shim JH, et al. Recurrences of hepatocellular carcinoma following complete remission by transarterial chemoembolization or radiofrequency therapy: focused on the recurrence patterns. Hepatol Res. 2013;43:1304–12.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Li L, Zhang J, Liu X, Li X, Jiao B, Kang T. Clinical outcomes of radiofrequency ablation and surgical resection for small hepatocellular carcinoma: a meta-analysis. J Gastroenterol Hepatol. 2012;27:51–8.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Liu L, Wang Z, Jiang S, Shao B, Liu J, Zhang S, et al. Perioperative allogenenic blood transfusion is associated with worse clinical outcomes for hepatocellular carcinoma: a meta-analysis. PLoS ONE ONE. 2013;8:e64261.CrossRefGoogle Scholar
  47. 47.
    Xun Y, Tian H, Hu L, Yan P, Yang K, Guo T. The impact of perioperative allogeneic blood transfusion on prognosis of hepatocellular carcinoma after radical hepatectomy: a systematic review and meta-analysis of cohort studies. Medicine. 2018;97:e12911.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Masayo Tsukamoto
    • 1
  • Katsunori Imai
    • 1
    Email author
  • Yo-ichi Yamashita
    • 1
  • Yuki Kitano
    • 1
  • Hirohisa Okabe
    • 1
  • Shigeki Nakagawa
    • 1
  • Hidetoshi Nitta
    • 1
  • Akira Chikamoto
    • 1
  • Takatoshi Ishiko
    • 1
  • Hideo Baba
    • 1
  1. 1.Department of Gastroenterological Surgery, Graduate School of Life SciencesKumamoto UniversityKumamotoJapan

Personalised recommendations