Skip to main content
SpringerLink
Log in

Radiofrequency ablation for hepatocellular carcinoma: the relationship between a new grading system for the ablative margin and clinical outcomes

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

In our previous study, we classified the radicality (R grading) of percutaneous radiofrequency ablation (RFA) therapy for single hepatocellular carcinoma (HCC) according to the extent of the ablated margin, and demonstrated that this grading system was useful for predicting local tumor progression (LTP) after RFA. The aim of this study was to measure the overall survival (OS), the recurrence free survival (RFS), and the distant recurrence (DR) rate for each R grade (A–D), and to examine the relationship between clinical outcome and R grading.

Methods

This study involved 368 patients with solitary HCC who had undergone RFA. The mean tumor diameter was 2.0 ± 0.7 cm. We calculated the post-RFA cumulative OS, RFS, and DR rate for each R grade and analyzed the factors contributing to clinical outcomes.

Results

In the multivariate analysis, significant factors were as follows: tumor size >2 cm, serum albumin >3.5 g/dL, prothrombin time >70 %, HCC recurrence within 1 year, and R grading (grade A) in OS; cause of liver disease (hepatitis B), gamma glutamyl transpeptidase (GGT) >80 IU/L, platelet count >10 × 104/mm3, and R grading (grade A or B) in RFS; GGT >80 IU/L, platelet count >10 × 104/mm3, and R grading (grade A or B) in DR. In patients with sufficient Lipiodol accumulation (n = 219), very similar results were obtained. However, in patients with grade A and B (n = 232), R grade was not a significant independent factor linked to OS, although grade A patients had lower LTP rate.

Conclusions

Our proposed R grading system appears to be useful for predicting clinical outcomes after RFA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Rossi S, Di Stasi M, Buscarini E, Quaretti P, Garbagnati F, Squassante L, et al. Percutaneous RF interstitial thermal ablation in the treatment of hepatic cancer. Am J Roentgenol. 1996;167:759–68.

    Article  CAS  Google Scholar 

  2. Curley SA, Izzo F, Ellis LM, Nicolas Vauthey J, Vallone P. Radiofrequency ablation of hepatocellular carcinoma in 110 patients with cirrhosis. Ann Surg. 2000;232:1694–702.

    Article  Google Scholar 

  3. Allgaier HP, Deibert P, Zuber I, Olschewski M, Blum HE. Percutaneous radiofrequency interstitial thermal ablation of small hepatocellular carcinoma. Lancet. 1999;353:1676–7.

    Article  PubMed  CAS  Google Scholar 

  4. Bosch FX, Ribes J, Borras J. Epidemiology of primary liver cancer. Semin Liver Dis. 1999;19:271–85.

    Article  PubMed  CAS  Google Scholar 

  5. Lencioni R. Loco-regional treatment of hepatocellular carcinoma. Hepatology. 2010;52:762–773.

    Google Scholar 

  6. Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, et al. Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology. 2006;131(2):461–9.

    Article  PubMed  CAS  Google Scholar 

  7. Van de Wiele C. Radioembolization of hepatocellular carcinoma. Curr Drug Discov Technol. 2010;7(4):247–52.

    Article  PubMed  Google Scholar 

  8. Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Nakashima O, et al. Management of hepatocellular carcinoma in Japan: consensus-based clinical practice guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis. 2011;29(3):339–64.

    Article  PubMed  Google Scholar 

  9. Izumi N. Recent advances of radiofrequency ablation for early hepatocellular carcinoma. J Gastroenterol Hepatol. 2011;26(Suppl 1):115–22.

    Article  PubMed  Google Scholar 

  10. Kudo M. Radiofrequency ablation for hepatocellular carcinoma: updated review in 2010. Oncology. 2010;78(Suppl 1):113–24.

    Article  PubMed  Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. Zhou WP, Lai EC, Li AJ, Fu SY, Zhou JP, Pan ZY, et al. A prospective, randomized, controlled trial of preoperative transarterial chemoembolization for resectable large hepatocellular carcinoma. Ann Surg. 2009;249:195–202.

    Article  PubMed  Google Scholar 

  13. Bruix J, Sherman M, Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208–36.

    Article  PubMed  Google Scholar 

  14. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC. Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut. 2005;54:1151–6.

    Article  PubMed  CAS  Google Scholar 

  15. Shiina S, Teratani T, Obi S, Sato S, Tateishi R, Fujishima T, et al. A randomized controlled trial or radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology. 2005;129:122–30.

    Article  PubMed  Google Scholar 

  16. Lencioni RA, Allgaier HP, Cioni D, Olschewski M, Deibert P, Crocetti L, et al. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection. Radiology. 2003;228:235–40.

    Article  PubMed  Google Scholar 

  17. Tiong L, Maddern GJ. Systematic review and meta-analysis of survival and disease recurrence after radiofrequency ablation for hepatocellular carcinoma. Br J Surg. 2011;98(9):1210–24.

    Article  PubMed  CAS  Google Scholar 

  18. Arii S, Tanaka J, Yamazoe Y, Minematsu S, Morino T, Fujita K, et al. Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy. Cancer. 1992;69:913–9.

    Article  PubMed  CAS  Google Scholar 

  19. Nagao T, Inoue S, Goto S, Mizuta T, Omori Y, Kawano N, et al. Hepatic resection for hepatocellular carcinoma. Clinical features and long-term prognosis. Ann Surg. 1987;205:33–40.

    Article  PubMed  CAS  Google Scholar 

  20. Takahashi S, Kudo M, Chung H, Inoue T, Ishikawa E, Kitai S, et al. Initial treatment is essential to improve survival in patients with hepatocellular carcinoma who underwent curative radiofrequency ablation therapy. Oncology. 2007;72(Suppl 1):98–103.

    Article  PubMed  Google Scholar 

  21. Morimoto M, Numata K, Sugimori K, Shirato K, Kokawa A, Oka H, et al. Successful initial ablation therapy contributes to survival in patients with hepatocellular carcinoma. World J Gastroenterol. 2007;13:1003–9.

    PubMed  CAS  Google Scholar 

  22. Sala M, Llovet JM, Vilana R, Bianchi L, Solé M, Ayuso C, et al. Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma. Hepatology. 2004;40:1352–60.

    Article  PubMed  Google Scholar 

  23. Nishikawa H, Inuzuka T, Takeda H, Nakajima J, Sakamoto A, Henmi S, et al. Percutaneous radiofrequency ablation therapy for hepatocellular carcinoma: a proposed new grading system for the ablative margin and prediction of local tumor progression and its validation. J Gastroenterol. 2011;46(12):1418–26.

    Article  PubMed  Google Scholar 

  24. Hayashi M, Matsui O, Ueda K, Kawamori Y, Gabata T, Kadoya M. Progression to hypervascular hepatocellular carcinoma: correlation with intranodular blood supply evaluated with CT during intraarterial injection of contrast material. Radiology. 2002;225(1):143–9.

    Article  PubMed  Google Scholar 

  25. Sacks D, McClenny T, Cardella J, Lewis C. Society of interventional radiology clinical practice guidelines. J Vasc Interv Radiol. 2003;14:S199–202.

    Article  PubMed  Google Scholar 

  26. Rossi S, Ravetta V, Rosa L, Ghittoni G, Viera FT, Garbagnati F, et al. Repeated radiofrequency ablation for management of patients with cirrhosis with small hepatocellular carcinomas: a long-term cohort study. Hepatology. 2011;53(1):136–47.

    Article  PubMed  Google Scholar 

  27. Liu CH, Arellano RS, Uppot RN, Samir AE, Gervais DA, Mueller PR. Radiofrequency ablation of hepatic tumors: effect of post-ablation margin on local tumor progression. Eur Radiol. 2010;20:877–85.

    Article  PubMed  Google Scholar 

  28. Kim YS, Rhim H, Cho OK, Koh BH, Kim Y. Intrahepatic recurrence after percutaneous radiofrequency ablation of hepatocellular carcinoma: analysis of the pattern and risk factors. Eur J Radiol. 2006;59:432–41.

    Article  PubMed  CAS  Google Scholar 

  29. Kim YS, Lee WJ, Rhim H, Lim HK, Choi D, Lee JY. The minimal ablative margin of radiofrequency ablation of hepatocellular carcinoma (> 2 and < 5 cm) needed to prevent local tumor progression: 3D quantitative assessment using CT image fusion. Am J Roentgenol. 2010;195:758–65.

    Article  Google Scholar 

  30. Tateishi R, Shiina S, Teratani T, Obi S, Sato S, Koike Y, et al. Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1000 cases. Cancer. 2005;103:1201–9.

    Article  PubMed  Google Scholar 

  31. Murakami T, Ishimaru H, Sakamoto I, Uetani M, Matsuoka Y, Daikoku M, et al. Percutaneous radiofrequency ablation and transcatheter arterial chemoembolization for hypervascular hepatocellular carcinoma: rate and risk factors for local recurrence. Cardiovasc Intevent Radiol. 2007;30:696–704.

    Article  Google Scholar 

  32. Nakazawa T, Kokubu S, Shibuya A, Ono K, Watanabe M, Hidaka H, et al. Radiofrequency ablation of hepatocellular carcinoma: correlation between local tumor progression after ablation and ablative margin. AJR Am J Roentgenol. 2007;188:480–8.

    Article  PubMed  Google Scholar 

  33. Pompili M, Rapaccini GL, Covino M, Pignataro G, Caturelli E, Siena DA, et al. Prognostic factors for survival in patients with compensated cirrhosis and small hepatocellular carcinoma after percutaneous ethanol injection therapy. Cancer. 2001;92:126–35.

    Article  PubMed  CAS  Google Scholar 

  34. Ebara M, Okabe S, Kita K, Sugiura N, Fukuda H, Yoshikawa M, et al. Percutaneous ethanol injection for small hepatocellular carcinoma: therapeutic efficacy based on 20-year observation. J Hepatol. 2005;43:458–64.

    Article  PubMed  CAS  Google Scholar 

  35. Peng ZW, Zhang YJ, Chen MS, Liang HH, Li JQ, Zhang YQ, et al. Risk factors of survival after percutaneous radiofrequency ablation of hepatocellular carcinoma. Surg Oncol. 2008;17(1):23–31.

    Article  PubMed  Google Scholar 

  36. Morimoto M, Numata K, Kondou M, Nozaki A, Morita S, Tanaka K. Midterm outcomes in patients with intermediate-sized hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of radiofrequency ablation combined with transcatheter arterial chemoembolization. Cancer. 2010;116(23):5452–60.

    Article  PubMed  Google Scholar 

  37. Lautz HU, Selberg O, Körber J, Bürger M, Müller MJ. Protein-calorie malnutrition in liver cirrhosis. Clin Investig. 1992;70(6):478–86.

    Article  PubMed  CAS  Google Scholar 

  38. Italian Multicentre Cooperative Project on Nutrition in Liver Cirrhosis. Nutritional status in cirrhosis. J Hepatol. 1994;21:317–35.

    Article  Google Scholar 

  39. Ishikawa T, Michitaka I, Kamimura H, Higuchi K, Kubota T, Seki K, et al. Oral branched-chain amino acids administration improves impaired liver dysfunction after radiofrequency ablation therapy for hepatocellular carcinoma. Hepatogastroenterology. 2009;56:1491–5.

    PubMed  CAS  Google Scholar 

  40. Mazzaferro V, Romito R, Schiavo M, Mariani L, Camerini T, Bhoori S, et al. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology. 2006;44:1543–54.

    Article  PubMed  CAS  Google Scholar 

  41. Goto T, Yoshida H, Tateishi R, Enooku K, Goto E, Sato T, et al. Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation. Hepatol Int. 2011;5(3):767–73.

    Article  PubMed  Google Scholar 

  42. Chuma M, Hige S, Kamiyama T, Meguro T, Nagasaka A, Nakanishi K, et al. The influence of hepatitis B DNA level and antiviral therapy on recurrence after initial curative treatment in patients with hepatocellular carcinoma. J Gastroenterol. 2009;44(9):991–9.

    Article  PubMed  CAS  Google Scholar 

  43. Shiratori Y, Shiina S, Teratani T, Imamura M, Obi S, Sato S, et al. Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus. Ann Intern Med. 2003;138:299–306.

    Article  PubMed  Google Scholar 

  44. Shimomura S, Ikeda N, Saito M, Ishii A, Takashima T, Sakai Y, et al. Long-term interferon therapy after radiofrequency ablation is effective in treating patients with HCV-associated hepatocellular carcinoma. Hepatol Int. 2010;5(1):559–66.

    Article  PubMed  Google Scholar 

  45. Kudo M, Sakaguchi Y, Chung H, Hatanaka K, Hagiwara S, Ishikawa E, et al. Long-term interferon maintenance therapy improves survival in patients with HCV-related hepatocellular carcinoma after curative radiofrequency ablation. A matched case–control study. Oncology. 2007;72(Suppl 1):132–8.

    Article  PubMed  CAS  Google Scholar 

  46. Yao D, Jiang D, Huang Z, Lu J, Tao Q, Yu Z, et al. Abnormal expression of hepatoma specific gamma-glutamyl transferase and alteration of gamma-glutamyl transferase gene methylation status in patients with hepatocellular carcinoma. Cancer. 2000;88(4):761–9.

    Article  PubMed  CAS  Google Scholar 

  47. Zhang JB, Chen Y, Zhang B, Xie X, Zhang L, Ge N, et al. Prognostic significance of serum gamma-glutamyl transferase in patients with intermediate hepatocellular carcinoma treated with transcatheter arterial chemoembolization. Eur J Gastroenterol Hepatol. 2011;23(9):787–93.

    Article  PubMed  Google Scholar 

  48. Ju MJ, Qiu SJ, Fan J, Zhou J, Gao Q, Cai MY, et al. Preoperative serum gamma-glutamyl transferase to alanine aminotransferase ratio is a convenient prognostic marker for Child-Pugh A hepatocellular carcinoma after operation. J Gastroenterol. 2009;44(6):635–42.

    Article  PubMed  CAS  Google Scholar 

  49. Amano H, Tashiro H, Oshita A, Kobayashi T, Tanimoto Y, Kuroda S, et al. Significance of platelet count in the outcomes of hepatectomized patients with hepatocellular carcinoma exceeding the Milan criteria. J Gastrointest Surg. 2011;15(7):1173–81.

    Article  PubMed  Google Scholar 

  50. Okada S, Shimada K, Yamamoto J, Takayama T, Kosuge T, Yamasaki S, et al. Predictive factors for postoperative recurrence of hepatocellular carcinoma. Gastroenterology. 1994;106(6):1618–24.

    PubMed  CAS  Google Scholar 

  51. Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38(2):200–7.

    Article  PubMed  Google Scholar 

  52. Takayama T, Makuuchi M, Hasegawa K. Single HCC smaller than 2 cm: surgery or ablation?: surgeon’s perspective. J Hepatobiliary Pancreat Sci. 2010;17(4):422–4.

    Article  PubMed  Google Scholar 

  53. 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(4):589–94.

    Article  PubMed  Google Scholar 

  54. Koda M, Tokunaga S, Miyoshi K, Kishina M, Fujise Y, Kato J, et al. Assessment of ablative margin by unenhanced magnetic resonance imaging after radiofrequency ablation for hepatocelluar carcinoma. Eur J Radiol. 2012;81(10):2730–6.

    Article  PubMed  Google Scholar 

  55. Tokunaga S, Koda M, Matono T, Sugihara T, Nagahara T, Ueki M, et al. Assessment of ablative margin by MRI with ferucarbotran in radiofrequency ablation for liver cancer: comparison with enhanced CT. Br J Radiol. 1014;2012(85):745–52.

    Google Scholar 

  56. Shiina S, Tateishi R, Arano T, Uchino K, Enooku K, Nakagawa H, et al. Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J Gastroenterol. 2012;107(4):569–77.

    Article  PubMed  CAS  Google Scholar 

  57. Shibata T, Isoda H, Hirokawa Y, Arizono S, Shimada K, Togashi K. Small hepatocelluar carcinoma: is radiofrequency ablation combined with transcatheter arterial chemoembolization more effective than radiofrequency ablation alone for treatment? Radiology. 2009;252(3):905–13.

    Article  PubMed  Google Scholar 

  58. Wang W, Shi J, Xie WF. Transcatheter chemoembolization in combination with percutaneous ablation therapy in unresectable hepatocellular carcinoma: a meta-analysis. Liver Int. 2010;30(5):741–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Haruko Takada for data collection.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka, 543-0027, Japan

    Hiroki Nishikawa, Yukio Osaki, Eriko Iguchi, Haruhiko Takeda, Fumihiro Matsuda, Jun Nakajima, Azusa Sakamoto, Keiichi Hatamaru, Sumio Saito, Akihiro Nasu, Ryuichi Kita & Toru Kimura

Authors
  1. Hiroki Nishikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yukio Osaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eriko Iguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haruhiko Takeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fumihiro Matsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Azusa Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Keiichi Hatamaru
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sumio Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Akihiro Nasu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ryuichi Kita
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Toru Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroki Nishikawa.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 120 kb)

Supplementary material 2 (DOC 107 kb)

Supplementary material 3 (DOC 92 kb)

Supplementary material 4 (DOC 51 kb)

535_2012_690_MOESM5_ESM.tif

Supplemental Fig. 1 Cumulative local tumor progression (LTP) rates according to R grading. In terms of LTP, the results obtained were almost identical to our previous study, that is, a more complete and a larger ablation margin was associated with a lower rate of LTP (Grade A vs. Grade B, P = 0.008; Grade B vs. Grade C, P <0.001; Grade C vs. Grade D, P = 0.010; Grade A vs. Grade C, P <0.001; Grade A vs. Grade D, P <0.001; Grade B vs. Grade D, P <0.001; and overall significance, P < 0.001) Supplementary material 5 (TIFF 98 kb)

535_2012_690_MOESM6_ESM.tif

Supplemental Fig. 2 Cumulative local tumor progression (LTP) rates according to R grading in patients with sufficient lipiodol accumulation. In terms of LTP, differences between individual grades reached statistical significance, indicating that a more complete and a larger ablation margin was associated with a favorable LTP rate (Grade A vs. Grade B, P = 0.039; Grade B vs. Grade C, P <0.001; Grade C vs. Grade D, P = 0.117; Grade A vs. Grade C, P <0.001; Grade A vs. Grade D, P <0.001; Grade B vs. Grade D, P <0.001; and overall significance, P <0.001) Supplementary material 6 (TIFF 82 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nishikawa, H., Osaki, Y., Iguchi, E. et al. Radiofrequency ablation for hepatocellular carcinoma: the relationship between a new grading system for the ablative margin and clinical outcomes. J Gastroenterol 48, 951–965 (2013). https://doi.org/10.1007/s00535-012-0690-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-012-0690-0

Keywords

Search

Navigation