Radiofrequency ablation using internally cooled wet electrodes in bipolar mode for the treatment of recurrent hepatocellular carcinoma after locoregional treatment: A randomized prospective comparative study

Jae Won Choi, Jeong Min Lee, Dong Ho Lee, Jung-Hwan Yoon, Yoon Jun Kim, Jeong-Hoon Lee, Su Jong Yu, Eun Ju Cho, Jae Won Choi, Jeong Min Lee, Dong Ho Lee, Jung-Hwan Yoon, Yoon Jun Kim, Jeong-Hoon Lee, Su Jong Yu, Eun Ju Cho

Abstract

Objective: This study aimed to compare the efficacy between bipolar radiofrequency ablation (RFA), using twin internally cooled wet (TICW) electrodes, and switching monopolar RFA, using separable clustered (SC) electrodes, in the treatment of recurrent hepatocellular carcinoma (HCC) after locoregional treatment.

Materials and methods: In this single-center, two-arm, parallel-group, randomized controlled study, we performed a 1:1 random allocation on eligible patients with recurrent HCC after locoregional treatment, to receive TICW-RFA or SC-RFA. The primary endpoint was the minimum diameter of the ablation zone per unit ablation time. Secondary endpoints included other technical parameters, complication rate, technical success and technique efficacy, and clinical outcomes.

Results: Enrolled patients were randomly assigned to the TICW-RFA group (n = 40) or SC-RFA group (n = 37). The two groups did not show significant differences in the primary endpoint, the minimum diameter of the ablation zone per unit ablation time was 2.71 ± 0.98 mm/min and 2.61 ± 0.96 mm/min in the TICW-RFA and SC-RFA groups, respectively (p = 0.577). Total RF energy delivery (11.75 ± 9.04 kcal vs. 22.61 ± 12.98 kcal, p < 0.001) and energy delivery per unit time (0.81 ± 0.49 kcal/min vs. 1.45 ± 0.42 kcal/min, p < 0.001) of the TICW-RFA group were less than those of the SC-RFA group. No procedure-related death or major complications occurred. Technical success was achieved in all patients in both groups, and technique efficacy rates were 100% (46/46) in the TICW-RFA group and 95.0% (38/40) in the SC-RFA group (p = 0.213). The 1-year and 2-year cumulative LTP rates were 11.8% and 24.2%, respectively, in the TICW-RFA group, and 8.6% and 18.1%, respectively, in the SC-RFA group (p = 0.661).

Conclusion: In this single-center randomized controlled study from a Korean tertiary referral hospital, TICW-RFA demonstrated similar therapeutic efficacy and safety profile for recurrent HCC after locoregional treatment compared with SC-RFA.

Trial registration: ClinicalTrials.gov (NCT03806218).

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: J.M.L. Activities related to the present article: grants from RF Medical Co., Ltd. Activities not related to the present article: grants from Guerbet, Bayer, Samsung Medison, CMS, Imaging Solution Korea, GE Healthcare, Philips Healthcare, and Canon Healthcare. Other authors have declared that no competing interests exist. This do not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Flow chart of the study…
Fig 1. Flow chart of the study population.
Fig 2. Photographs of (A) twin internally…
Fig 2. Photographs of (A) twin internally cooled wet (TICW) electrodes (CWTN-T, RF Medical, Seoul, Korea) and (B) separable clustered (SC) electrodes with three active tips (Octopus, STARmed, Goyang, Korea).
Fig 3. Cumulative LTP rates after RFA…
Fig 3. Cumulative LTP rates after RFA of (A) overall recurrent nodules and (B) nodules that presented as LTP.
Fig 4. Comparison of clinical outcomes between…
Fig 4. Comparison of clinical outcomes between TICW-RFA and SC-RFA groups.
(A) LTP-free survival and (B) RFS in patients treated with TICW-RFA or SC-RFA.

References

    1. European Association for the Study of the Liver. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69: 182–236. 10.1016/j.jhep.2018.03.019
    1. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67: 358–380. 10.1002/hep.29086
    1. Omata M, Cheng A-L, Kokudo N, Kudo M, Lee JM, Jia J, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11: 317–370. 10.1007/s12072-017-9799-9
    1. 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: 136–147. 10.1002/hep.23965
    1. Nishikawa H, Osaki Y, Iguchi E, Takeda H, Ohara Y, Sakamoto A, et al. Percutaneous radiofrequency ablation therapy for recurrent hepatocellular carcinoma. Anticancer Res. 2012;32: 5059–5065.
    1. Lee DH, Lee JM, Lee JY, Kim SH, Han JK, Choi BI. Radiofrequency ablation for intrahepatic recurrent hepatocellular carcinoma: long-term results and prognostic factors in 168 patients with cirrhosis. Cardiovasc Intervent Radiol. 2014;37: 705–715. 10.1007/s00270-013-0708-x
    1. Kim Y-S, Lim HK, Rhim H, Lee MW, Choi D, Lee WJ, et al. Ten-year outcomes of percutaneous radiofrequency ablation as first-line therapy of early hepatocellular carcinoma: analysis of prognostic factors. J Hepatol. 2013;58: 89–97. 10.1016/j.jhep.2012.09.020
    1. N’Kontchou G, Mahamoudi A, Aout M, Ganne-Carrié N, Grando V, Coderc E, et al. Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis. Hepatology. 2009;50: 1475–1483. 10.1002/hep.23181
    1. Lee DH, Lee JM, Lee JY, Kim SH, Yoon JH, Kim YJ, et al. Radiofrequency ablation of hepatocellular carcinoma as first-line treatment: long-term results and prognostic factors in 162 patients with cirrhosis. Radiology. 2014;270: 900–909. 10.1148/radiol.13130940
    1. 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: 480–488. 10.2214/AJR.05.2079
    1. Kim Y-S, 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. AJR Am J Roentgenol. 2010;195: 758–765. 10.2214/AJR.09.2954
    1. Yoon JH, Lee JM, Klotz E, Woo H, Yu MH, Joo I, et al. Prediction of Local Tumor Progression after Radiofrequency Ablation (RFA) of Hepatocellular Carcinoma by Assessment of Ablative Margin Using Pre-RFA MRI and Post-RFA CT Registration. Korean J Radiol. 2018;19: 1053 10.3348/kjr.2018.19.6.1053
    1. 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: E335–45. 10.1111/hepr.12313
    1. Lam VW-T, Ng KK-C, Chok KS-H, Cheung T-T, Yuen J, Tung H, et al. Risk factors and prognostic factors of local recurrence after radiofrequency ablation of hepatocellular carcinoma. J Am Coll Surg. 2008;207: 20–29. 10.1016/j.jamcollsurg.2008.01.020
    1. Lam VW-T, Ng KK, Chok KS-H, Cheung T-T, Yuen J, Tung H, et al. Incomplete ablation after radiofrequency ablation of hepatocellular carcinoma: analysis of risk factors and prognostic factors. Ann Surg Oncol. 2008;15: 782–790. 10.1245/s10434-007-9733-9
    1. Rozenblum N, Zeira E, Scaiewicz V, Bulvik B, Gourevitch S, Yotvat H, et al. Oncogenesis: An “Off-Target” Effect of Radiofrequency Ablation. Radiology. 2015;276: 426–432. 10.1148/radiol.2015141695
    1. Ahmed M, Kumar G, Moussa M, Wang Y, Rozenblum N, Galun E, et al. Hepatic Radiofrequency Ablation-induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition. Radiology. 2016;279: 103–117. 10.1148/radiol.2015150080
    1. Kong J, Kong J, Pan B, Ke S, Dong S, Li X, et al. Insufficient radiofrequency ablation promotes angiogenesis of residual hepatocellular carcinoma via HIF-1α/VEGFA. PLoS One. 2012;7: e37266 10.1371/journal.pone.0037266
    1. Nijkamp MW, van der Bilt JDW, de Bruijn MT, Molenaar IQ, Voest EE, van Diest PJ, et al. Accelerated perinecrotic outgrowth of colorectal liver metastases following radiofrequency ablation is a hypoxia-driven phenomenon. Ann Surg. 2009;249: 814–823. 10.1097/SLA.0b013e3181a38ef5
    1. Zen C, Zen Y, Mitry RR, Corbeil D, Karbanová J, O’Grady J, et al. Mixed phenotype hepatocellular carcinoma after transarterial chemoembolization and liver transplantation. Liver Transpl. 2011;17: 943–954. 10.1002/lt.22314
    1. Sergio A, Cristofori C, Cardin R, Pivetta G, Ragazzi R, Baldan A, et al. Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness. Am J Gastroenterol. 2008;103: 914–921. 10.1111/j.1572-0241.2007.01712.x
    1. Lee JM, Han JK, Kim HC, Choi YH, Kim SH, Choi JY, et al. Switching monopolar radiofrequency ablation technique using multiple, internally cooled electrodes and a multichannel generator: ex vivo and in vivo pilot study. Invest Radiol. 2007;42: 163–171. 10.1097/01.rli.0000252495.44818.b3
    1. Laeseke PF, Frey TM, Brace CL, Sampson LA, Winter TC 3rd, Ketzler JR, et al. Multiple-electrode radiofrequency ablation of hepatic malignancies: initial clinical experience. AJR Am J Roentgenol. 2007;188: 1485–1494. 10.2214/AJR.06.1004
    1. Mulier S, Miao Y, Mulier P, Dupas B, Pereira P, de Baere T, et al. Electrodes and multiple electrode systems for radiofrequency ablation: a proposal for updated terminology. Eur Radiol. 2005;15: 798–808. 10.1007/s00330-004-2584-x
    1. Yoon JH, Lee JM, Woo S, Hwang EJ, Hwang I, Choi W, et al. Switching bipolar hepatic radiofrequency ablation using internally cooled wet electrodes: comparison with consecutive monopolar and switching monopolar modes. Br J Radiol. 2015;88: 20140468 10.1259/bjr.20140468
    1. Martin RCG, Scoggins CR, McMasters KM. Safety and efficacy of microwave ablation of hepatic tumors: a prospective review of a 5-year experience. Ann Surg Oncol. 2010;17: 171–178. 10.1245/s10434-009-0686-z
    1. Poulou LS, Botsa E, Thanou I, Ziakas PD, Thanos L. Percutaneous microwave ablation vs radiofrequency ablation in the treatment of hepatocellular carcinoma. World J Hepatol. 2015;7: 1054–1063. 10.4254/wjh.v7.i8.1054
    1. Ding J, Jing X, Liu J, Wang Y, Wang F, Wang Y, et al. Comparison of two different thermal techniques for the treatment of hepatocellular carcinoma. Eur J Radiol. 2013;82: 1379–1384. 10.1016/j.ejrad.2013.04.025
    1. Yamakado K, Nakatsuka A, Ohmori S, Shiraki K, Nakano T, Ikoma J, et al. Radiofrequency ablation combined with chemoembolization in hepatocellular carcinoma: treatment response based on tumor size and morphology. J Vasc Interv Radiol. 2002;13: 1225–1232. 10.1016/s1051-0443(07)61969-1
    1. Shibata T, Isoda H, Hirokawa Y, Arizono S, Shimada K, Togashi K. Small hepatocellular carcinoma: is radiofrequency ablation combined with transcatheter arterial chemoembolization more effective than radiofrequency ablation alone for treatment? Radiology. 2009;252: 905–913. 10.1148/radiol.2523081676
    1. Feng X, Xu R, Du X, Dou K, Qin X, Xu J, et al. Combination therapy with sorafenib and radiofrequency ablation for BCLC Stage 0-B1 hepatocellular carcinoma: a multicenter retrospective cohort study. Am J Gastroenterol. 2014;109: 1891–1899. 10.1038/ajg.2014.343
    1. Duffy AG, Ulahannan SV, Makorova-Rusher O, Rahma O, Wedemeyer H, Pratt D, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol. 2017;66: 545–551. 10.1016/j.jhep.2016.10.029
    1. Lee DH, Lee JM. Recent Advances in the Image-Guided Tumor Ablation of Liver Malignancies: Radiofrequency Ablation with Multiple Electrodes, Real-Time Multimodality Fusion Imaging, and New Energy Sources. Korean J Radiol. 2018;19: 545–559. 10.3348/kjr.2018.19.4.545
    1. Lee JM, Han JK, Kim SH, Lee JY, Shin KS, Han CJ, et al. Optimization of wet radiofrequency ablation using a perfused-cooled electrode: a comparative study in ex vivo bovine livers. Korean J Radiol. 2004;5: 250–257. 10.3348/kjr.2004.5.4.250
    1. Krücker J, Xu S, Venkatesan A, Locklin JK, Amalou H, Glossop N, et al. Clinical utility of real-time fusion guidance for biopsy and ablation. J Vasc Interv Radiol. 2011;22: 515–524. 10.1016/j.jvir.2010.10.033
    1. Kim JH, Kim PN, Won HJ, Shin YM. Percutaneous radiofrequency ablation using internally cooled wet electrodes for the treatment of hepatocellular carcinoma. AJR Am J Roentgenol. 2012;198: 471–476. 10.2214/AJR.11.6583
    1. Chang W, Lee JM, Lee DH, Yoon JH, Kim YJ, Yoon JH, et al. Comparison of switching bipolar ablation with multiple cooled wet electrodes and switching monopolar ablation with separable clustered electrode in treatment of small hepatocellular carcinoma: A randomized controlled trial. PLoS One. 2018;13: e0192173 10.1371/journal.pone.0192173
    1. Woo S, Lee JM, Yoon JH, Joo I, Kim SH, Lee JY, et al. Small- and medium-sized hepatocellular carcinomas: monopolar radiofrequency ablation with a multiple-electrode switching system-mid-term results. Radiology. 2013;268: 589–600. 10.1148/radiol.13121736
    1. Choi JW, Lee JM, Lee DH, Yoon J-H, Suh K-S, Yoon J-H, et al. Switching Monopolar Radiofrequency Ablation Using a Separable Cluster Electrode in Patients with Hepatocellular Carcinoma: A Prospective Study. PLoS One. 2016;11: e0161980 10.1371/journal.pone.0161980
    1. Ahn SJ, Lee JM, Lee DH, Lee SM, Yoon J-H, Kim YJ, et al. Real-time US-CT/MR fusion imaging for percutaneous radiofrequency ablation of hepatocellular carcinoma. J Hepatol. 2017;66: 347–354. 10.1016/j.jhep.2016.09.003
    1. Lee MW. Fusion imaging of real-time ultrasonography with CT or MRI for hepatic intervention. Ultrasonography. 2014;33: 227–239. 10.14366/usg.14021
    1. Nam SY, Rhim H, Kang TW, Lee MW, Kim Y-S, Choi D, et al. Percutaneous radiofrequency ablation for hepatic tumors abutting the diaphragm: clinical assessment of the heat-sink effect of artificial ascites. AJR Am J Roentgenol. 2010;194: W227–31. 10.2214/AJR.09.2979
    1. Ahmed M, Solbiati L, Brace CL, Breen DJ, Callstrom MR, Charboneau JW, et al. Image-guided tumor ablation: standardization of terminology and reporting criteria—a 10-year update. Radiology. 2014;273: 241–260. 10.1148/radiol.14132958
    1. Choi H, Loyer EM, DuBrow RA, Kaur H, David CL, Huang S, et al. Radio-frequency ablation of liver tumors: assessment of therapeutic response and complications. Radiographics. 2001;21 Spec No: S41–54. 10.1148/radiographics.21.suppl_1.g01oc08s41
    1. Sacks D, McClenny TE, Cardella JF, Lewis CA. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol. 2003;14: S199–202. 10.1097/01.rvi.0000094584.83406.3e
    1. Kim JH, Won HJ, Shin YM, Kim K-A, Kim PN. Radiofrequency ablation for the treatment of primary intrahepatic cholangiocarcinoma. AJR Am J Roentgenol. 2011;196: W205–9. 10.2214/AJR.10.4937
    1. Lim HK, Choi D, Lee WJ, Kim SH, Lee SJ, Jang HJ, et al. Hepatocellular carcinoma treated with percutaneous radio-frequency ablation: evaluation with follow-up multiphase helical CT. Radiology. 2001;221: 447–454. 10.1148/radiol.2212010446
    1. Kang TW, Lim HK, Lee MW, Kim Y-S, Rhim H, Lee WJ, et al. Aggressive Intrasegmental Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation: Risk Factors and Clinical Significance. Radiology. 2015;276: 274–285. 10.1148/radiol.15141215
    1. Yang W, Chen MH, Yin SS, Yan K, Gao W, Wang YB, et al. Radiofrequency ablation of recurrent hepatocellular carcinoma after hepatectomy: therapeutic efficacy on early- and late-phase recurrence. AJR Am J Roentgenol. 2006;186: S275–83. 10.2214/AJR.04.1573
    1. Lee JM, Han JK, Kim SH, Han CJ, An SK, Lee JY, et al. Wet radio-frequency ablation using multiple electrodes: comparative study of bipolar versus monopolar modes in the bovine liver. Eur J Radiol. 2005;54: 408–417. 10.1016/j.ejrad.2004.06.004
    1. Kim JH, Kim PN, Won HJ, Shin YM. Percutaneous radiofrequency ablation with internally cooled versus internally cooled wet electrodes for small subphrenic hepatocellular carcinomas. J Vasc Interv Radiol. 2013;24: 351–356. 10.1016/j.jvir.2012.11.025
    1. Hocquelet A, Aubé C, Rode A, Cartier V, Sutter O, Manichon AF, et al. Comparison of no-touch multi-bipolar vs. monopolar radiofrequency ablation for small HCC. J Hepatol. 2017;66: 67–74. 10.1016/j.jhep.2016.07.010
    1. Lee J, Lee JM, Yoon J-H, Lee JY, Kim SH, Lee JE, et al. Percutaneous radiofrequency ablation with multiple electrodes for medium-sized hepatocellular carcinomas. Korean J Radiol. 2012;13: 34–43. 10.3348/kjr.2012.13.1.34
    1. Mima K, Hayashi H, Imai K, Kuroki H, Nakagawa S, Okabe H, et al. High CD44s expression is associated with the EMT expression profile and intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy. J Hepatobiliary Pancreat Sci. 2013;20: 429–434. 10.1007/s00534-012-0580-0
    1. Choi D, Lim HK, Rhim H, Kim Y-S, Yoo BC, Paik SW, et al. Percutaneous radiofrequency ablation for recurrent hepatocellular carcinoma after hepatectomy: long-term results and prognostic factors. Ann Surg Oncol. 2007;14: 2319–2329. 10.1245/s10434-006-9220-8
    1. Peng Z-W, Zhang Y-J, Liang H-H, Lin X-J, Guo R-P, Chen M-S. Recurrent hepatocellular carcinoma treated with sequential transcatheter arterial chemoembolization and RF ablation versus RF ablation alone: a prospective randomized trial. Radiology. 2012;262: 689–700. 10.1148/radiol.11110637
    1. Chan ACY, Chan SC, Chok KSH, Cheung TT, Chiu DW, Poon RTP, et al. Treatment strategy for recurrent hepatocellular carcinoma: salvage transplantation, repeated resection, or radiofrequency ablation? Liver Transpl. 2013;19: 411–419. 10.1002/lt.23605
    1. Chen R, Gan Y, Ge N, Chen Y, Wang Y, Zhang B, et al. Transarterial Chemoembolization versus Radiofrequency Ablation for Recurrent Hepatocellular Carcinoma after Resection within Barcelona Clinic Liver Cancer Stage 0/A: A Retrospective Comparative Study. J Vasc Interv Radiol. 2016;27: 1829–1836. 10.1016/j.jvir.2016.06.010
    1. Lee JM, Kim SH, Han JK, Sohn KL, Choi BI. Ex Vivo Experiment of Saline-Enhanced Hepatic Bipolar Radiofrequency Ablation with a Perfused Needle Electrode: Comparison with Conventional Monopolar and Simultaneous Monopolar Modes. CardioVascular and Interventional Radiology. 2005. pp. 338–345. 10.1007/s00270-004-0177-3
    1. Kang TW, Lim HK, Cha DI. Aggressive tumor recurrence after radiofrequency ablation for hepatocellular carcinoma. Clin Mol Hepatol. 2017;23: 95–101. 10.3350/cmh.2017.0006
    1. Chang W, Lee JM, Lee SM, Han JK. No-Touch Radiofrequency Ablation: A Comparison of Switching Bipolar and Switching Monopolar Ablation in Bovine Liver. Korean J Radiol. 2017;18: 279–288. 10.3348/kjr.2017.18.2.279
    1. Seror O, N’Kontchou G, Van Nhieu JT, Rabahi Y, Nahon P, Laurent A, et al. Histopathologic comparison of monopolar versus no-touch multipolar radiofrequency ablation to treat hepatocellular carcinoma within Milan criteria. J Vasc Interv Radiol. 2014;25: 599–607. 10.1016/j.jvir.2013.11.025

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