Preoperative transcatheter arterial chemoembolization for surgical resection of huge hepatocellular carcinoma (≥ 10 cm): a multicenter propensity matching analysis

  • Chao Li
  • Ming-Da Wang
  • Lun Lu
  • Han Wu
  • Jiong-Jie Yu
  • Wan-Guang Zhang
  • Timothy M. Pawlik
  • Yao-Ming Zhang
  • Ya-Hao Zhou
  • Wei-Min Gu
  • Hong Wang
  • Ting-Hao Chen
  • Jun Han
  • Hao Xing
  • Zhen-Li Li
  • Wan Yee Lau
  • Meng-Chao Wu
  • Feng ShenEmail author
  • Tian YangEmail author
Original Article


Background and Aims

Surgical resection for hepatocellular carcinoma (HCC) is potentially curative, but long-term survival remains unsatisfactory. There is currently no effective neoadjuvant or adjuvant therapy for HCC. We sought to evaluate the impact of preoperative transcatheter arterial chemoembolization (TACE) on long-term prognosis after surgical resection of huge HCCs (≥ 10 cm).


Using a multicenter database, consecutive patients who underwent curative-intent resection for huge HCC without macrovascular invasion between 2004 and 2014 were identified. The association between preoperative TACE with perioperative outcomes, long-term overall survival (OS), and recurrence-free survival (RFS) was assessed before and after propensity score matching (PSM).


Among the 377 enrolled patients, 88 patients (23.3%) received preoperative TACE. The incidence of perioperative mortality and morbidity was comparable among patients who did and did not undergo preoperative TACE (3.4% vs. 2.4%, p= 0.704, and 33.0% vs. 31.1%, p= 0.749, respectively). PSM analysis created 84 matched pairs of patients. In examining the entire cohort as well as the PSM cohort, median OS (overall cohort: 32.8 vs. 22.3 months, p= 0.035, and PSM only: 32.8 vs. 18.1 months, p= 0.023, respectively) and RFS (12.9 vs. 6.4 months, p= 0.016, and 12.9 vs. 4.1 months, p= 0.009, respectively) were better among patients who underwent preoperative TACE vs. patients who did not. After adjustment for other confounding factors on multivariable analyses, preoperative TACE remained independently associated with a favorable OS and RFS after the resection of huge HCC.


Preoperative TACE did not increase perioperative morbidity or mortality, yet was associated with an improved OS and RFS after liver resection of huge HCC (≥ 10 cm).


Hepatocellular carcinoma Hepatectomy Transcatheter arterial chemoembolization Recurrence Survival 



Hepatocellular carcinoma


Transcatheter arterial chemoembolization


Propensity score matching


Overall survival


Recurrence-free survival


Randomized controlled trial


Radiofrequency ablation


Body mass index


American society of anesthesiologists


International normalized ratio


Hepatitis B virus




Computed tomography


Magnetic resonance imaging


Standard deviation


Hazard ratio

95% CI

95 Percent confidence interval



The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Author contributions

CL, M-DW, LL, HW, J-JY, and W-GZ contributed equally to this work. Dr. TY and FS had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: CL, M-DW, FS, and TY. Acquisition, analysis, or interpretation of data: CL, M-DW, HW, W-GZ, Y-MZ, Y-HZ, W-MG, HW, T-HC, JH, J-JY, HX, and Z-LL. Drafting of the manuscript: CL, M-DW, HW, J-JY, Z-LL, and TY. Critical revision of the manuscript for important intellectual content: LL, TMP, CL, WYL, TY, and FS. Statistical analysis: HX, J-JY, CL, M-DW, and TY. Obtained funding: TY and M-DW. Administrative, technical, or material support: WYL, W-GZ, Y-MZ, Y-HZ, W-MG, HW, T-HC, FS, and TY. Study supervision: WYL, M-CW, FS, and TY.


Funding for the study was provided by the National Natural Science Foundation of China (Nos. 81472284, 81672699, 81972726 for Dr. Yang and 81702334 for Dr. Wang) and Shanghai Pujiang Program (No. 16PJD004 for Dr. Yang).

Compliance with ethical standards

Conflict of interest

Chao Li, Ming‑Da Wang, Lun Lu, Han Wu, Jiong‑Jie Yu, Wan‑Guang Zhang, Timothy M. Pawlik, Yao‑Ming Zhang, Ya‑Hao Zhou, Wei‑Min Gu, Hong Wang, Ting‑Hao Chen, Jun Han, Hao Xing, Zhen‑Li Li, Wan Yee Lau, Meng‑Chao Wu, Feng Shen and Tian Yang declare that they have no conflict 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 Helsinki Declaration and its later amendments or comparable ethical standards. This study was conducted in accordance with the Declaration of Helsinki and the Ethical Guidelines for Clinical Studies of Eastern Hepatobiliary Surgery Hospital of Shanghai.

Informed consent

The study protocol was approved by the Institutional Review Board of all participating hospitals, and informed consent from the patients was waived. Written, informed consent for the data to be used for clinical researches was obtained from all enrolled patients.


  1. 1.
    Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301–1314CrossRefGoogle Scholar
  2. 2.
    Agrawal S, Belghiti J. Oncologic resection for malignant tumors of the liver. Ann Surg. 2011;253(4):656–665CrossRefGoogle Scholar
  3. 3.
    Poon RT, Fan ST, Wong J. Selection criteria for hepatic resection in patients with large hepatocellular carcinoma larger than 10 cm in diameter. J Am Coll Surg. 2002;194(5):592–602CrossRefGoogle Scholar
  4. 4.
    Pandey D, Lee KH, Wai CT, Wagholikar G, Tan KC. Long term outcome and prognostic factors for large hepatocellular carcinoma (10 cm or more) after surgical resection. Ann Surg Oncol. 2007;14(10):2817–2823CrossRefGoogle Scholar
  5. 5.
    Yang L, Xu J, Ou D, Wu W, Zeng Z. Hepatectomy for huge hepatocellular carcinoma: single institute’s experience. World J Surg. 2013;37(9):2189–2196CrossRefGoogle Scholar
  6. 6.
    Wakayama K, Kamiyama T, Yokoo H, et al. Huge hepatocellular carcinoma greater than 10 cm in diameter worsens prognosis by causing distant recurrence after curative resection. J Surg Oncol. 2017;115(3):324–329CrossRefGoogle Scholar
  7. 7.
    Portolani N, Coniglio A, Ghidoni S, et al. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg. 2006;243(2):229–235CrossRefGoogle Scholar
  8. 8.
    Tsochatzis EA, Germani G, Burroughs AK. Transarterial chemoembolization, transarterial chemotherapy, and intra-arterial chemotherapy for hepatocellular carcinoma treatment. Semin Oncol. 2010;37(2):89–93CrossRefGoogle Scholar
  9. 9.
    Majno PE, Adam R, Bismuth H, et al. Influence of preoperative transarterial lipiodol chemoembolization on resection and transplantation for hepatocellular carcinoma in patients with cirrhosis. Ann Surg. 1997;226(6):688–701 (discussion 701–703) CrossRefGoogle Scholar
  10. 10.
    Paye F, Jagot P, Vilgrain V, Farges O, Borie D, Belghiti J. Preoperative chemoembolization of hepatocellular carcinoma: a comparative study. Arch Surg. 1998;133(7):767–772CrossRefGoogle Scholar
  11. 11.
    Lu CD, Peng SY, Jiang XC, Chiba Y, Tanigawa N. Preoperative transcatheter arterial chemoembolization and prognosis of patients with hepatocellular carcinomas: retrospective analysis of 120 cases. World J Surg. 1999;23(3):293–300CrossRefGoogle Scholar
  12. 12.
    Gerunda GE, Neri D, Merenda R, et al. Role of transarterial chemoembolization before liver resection for hepatocarcinoma. Liver Transpl. 2000;6(5):619–626CrossRefGoogle Scholar
  13. 13.
    Zhang Z, Liu Q, He J, Yang J, Yang G, Wu M. The effect of preoperative transcatheter hepatic arterial chemoembolization on disease-free survival after hepatectomy for hepatocellular carcinoma. Cancer. 2000;89(12):2606–2612CrossRefGoogle Scholar
  14. 14.
    Luo YQ, Wang Y, Chen H, Wu MC. Influence of preoperative transcatheter arterial chemoembolization on liver resection in patients with resectable hepatocellular carcinoma. Hepatobil Pancreat Dis Int. 2002;1(4):523–526Google Scholar
  15. 15.
    Ochiai T, Sonoyama T, Hironaka T, Yamagishi H. Hepatectomy with chemoembolization for treatment of hepatocellular carcinoma. Hepatogastroenterology. 2003;50(51):750–755Google Scholar
  16. 16.
    Sugo H, Futagawa S, Beppu T, Fukasawa M, Kojima K. Role of preoperative transcatheter arterial chemoembolization for resectable hepatocellular carcinoma: relation between postoperative course and the pattern of tumor recurrence. World J Surg. 2003;27(12):1295–1299CrossRefGoogle Scholar
  17. 17.
    Sasaki A, Iwashita Y, Shibata K, Ohta M, Kitano S, Mori M. Preoperative transcatheter arterial chemoembolization reduces long-term survival rate after hepatic resection for resectable hepatocellular carcinoma. Eur J Surg Oncol. 2006;32(7):773–779CrossRefGoogle Scholar
  18. 18.
    Chen XP, Hu DY, Zhang ZW, et al. Role of mesohepatectomy with or without transcatheter arterial chemoembolization for large centrally located hepatocellular carcinoma. Dig Surg. 2007;24(3):208–213CrossRefGoogle Scholar
  19. 19.
    Choi GH, Kim DH, Kang CM, et al. Is preoperative transarterial chemoembolization needed for a resectable hepatocellular carcinoma. World J Surg. 2007;31(12):2370–2377CrossRefGoogle Scholar
  20. 20.
    Kim IS, Lim YS, Lee HC, Suh DJ, Lee YJ, Lee SG. Pre-operative transarterial chemoembolization for resectable hepatocellular carcinoma adversely affects post-operative patient outcome. Aliment Pharmacol Ther. 2008;27(4):338–345CrossRefGoogle Scholar
  21. 21.
    Lee KT, Lu YW, Wang SN, et al. The effect of preoperative transarterial chemoembolization of resectable hepatocellular carcinoma on clinical and economic outcomes. J Surg Oncol. 2009;99(6):343–350CrossRefGoogle Scholar
  22. 22.
    Yamashita Y, Takeishi K, Tsuijita E, et al. Beneficial effects of preoperative lipiodolization for resectable large hepatocellular carcinoma (≥ 5 cm in diameter). J Surg Oncol. 2012;106(4):498–503CrossRefGoogle Scholar
  23. 23.
    Nishikawa H, Arimoto A, Wakasa T, Kita R, Kimura T, Osaki Y. Effect of transcatheter arterial chemoembolization prior to surgical resection for hepatocellular carcinoma. Int J Oncol. 2013;42(1):151–160CrossRefGoogle Scholar
  24. 24.
    Shi HY, Wang SN, Wang SC, Chuang SC, Chen CM, Lee KT. Preoperative transarterial chemoembolization and resection for hepatocellular carcinoma: a nationwide Taiwan database analysis of long-term outcome predictors. J Surg Oncol. 2014;109(5):487–493CrossRefGoogle Scholar
  25. 25.
    Ha TY, Hwang S, Lee YJ, et al. Absence of benefit of transcatheter arterial chemoembolization (TACE) in patients with resectable solitary hepatocellular carcinoma. World J Surg. 2016;40(5):1200–1210CrossRefGoogle Scholar
  26. 26.
    Zhang YF, Guo RP, Zou RH, et al. Efficacy and safety of preoperative chemoembolization for resectable hepatocellular carcinoma with portal vein invasion: a prospective comparative study. Eur Radiol. 2016;26(7):2078–2088CrossRefGoogle Scholar
  27. 27.
    Jianyong L, Jinjing Z, Lunan Y, et al. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma. Sci Rep. 2017;7:41624CrossRefGoogle Scholar
  28. 28.
    Tao Q, He W, Li B, et al. Resection versus resection with preoperative transcatheter arterial chemoembolization for resectable hepatocellular carcinoma recurrence. J Cancer. 2018;9(16):2778–2785CrossRefGoogle Scholar
  29. 29.
    Wu CC, Ho YZ, Ho WL, Wu TC, Liu TJ, P’eng FK. Preoperative transcatheter arterial chemoembolization for resectable large hepatocellular carcinoma: a reappraisal. Br J Surg. 1995;82(1):122–126CrossRefGoogle Scholar
  30. 30.
    Yamasaki S, Hasegawa H, Kinoshita H, et al. A prospective randomized trial of the preventive effect of pre-operative transcatheter arterial embolization against recurrence of hepatocellular carcinoma. Jpn J Cancer Res. 1996;87(2):206–211CrossRefGoogle Scholar
  31. 31.
    Zhou WP, Lai EC, Li AJ, et al. A prospective, randomized, controlled trial of preoperative transarterial chemoembolization for resectable large hepatocellular carcinoma. Ann Surg. 2009;249(2):195–202CrossRefGoogle Scholar
  32. 32.
    Kaibori M, Tanigawa N, Kariya S, et al. A prospective randomized controlled trial of preoperative whole-liver chemolipiodolization for hepatocellular carcinoma. Dig Dis Sci. 2012;57(5):1404–1412CrossRefGoogle Scholar
  33. 33.
    Cheng X, Sun P, Hu QG, Song ZF, Xiong J, Zheng QC. Transarterial (chemo)embolization for curative resection of hepatocellular carcinoma: a systematic review and meta-analyses. J Cancer Res Clin Oncol. 2014;140(7):1159–1170CrossRefGoogle Scholar
  34. 34.
    Gao ZH, Bai DS, Jiang GQ, Jin SJ. Review of preoperative transarterial chemoembolization for resectable hepatocellular carcinoma. World J Hepatol. 2015;7(1):40–43CrossRefGoogle Scholar
  35. 35.
    Si T, Chen Y, Ma D, et al. Preoperative transarterial chemoembolization for resectable hepatocellular carcinoma in Asia area: a meta-analysis of random controlled trials. Scand J Gastroenterol. 2016;51(12):1512–1519CrossRefGoogle Scholar
  36. 36.
    Regimbeau JM, Farges O, Shen BY, Sauvanet A, Belghiti J. Is surgery for large hepatocellular carcinoma justified. J Hepatol. 1999;31(6):1062–1068CrossRefGoogle Scholar
  37. 37.
    Pawlik TM, Poon RT, Abdalla EK, et al. Critical appraisal of the clinical and pathologic predictors of survival after resection of large hepatocellular carcinoma. Arch Surg. 2005;140(5):450–457 (discussion 457–458) CrossRefGoogle Scholar
  38. 38.
    Zangos S, Eichler K, Balzer JO, et al. Large-sized hepatocellular carcinoma (HCC): a neoadjuvant treatment protocol with repetitive transarterial chemoembolization (TACE) before percutaneous MR-guided laser-induced thermotherapy (LITT). Eur Radiol. 2007;17(2):553–563CrossRefGoogle Scholar
  39. 39.
    Xue T, Le F, Chen R, et al. Transarterial chemoembolization for huge hepatocellular carcinoma with diameter over ten centimeters: a large cohort study. Med Oncol. 2015;32(3):64CrossRefGoogle Scholar
  40. 40.
    Rosenbaum PR, Rubin DB. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985;39:33–38Google Scholar
  41. 41.
    Rubin DB, Thomas N. Matching using estimated propensity scores: relating theory to practice. Biometrics. 1996;52(1):249–264CrossRefGoogle Scholar
  42. 42.
    Yang T, Lu JH, Lau WY, et al. Perioperative blood transfusion does not influence recurrence-free and overall survivals after curative resection for hepatocellular carcinoma: a propensity score matching analysis. J Hepatol. 2016;64(3):583–593CrossRefGoogle Scholar
  43. 43.
    Ye JZ, Chen JZ, Li ZH, et al. Efficacy of postoperative adjuvant transcatheter arterial chemoembolization in hepatocellular carcinoma patients with microvascular invasion. World J Gastroenterol. 2017;23(41):7415–7424CrossRefGoogle Scholar
  44. 44.
    Wang YY, Wang LJ, Xu D, Liu M, Wang HW, Wang K, Zhu X, Xing BC. Postoperative adjuvant transcatheter arterial chemoembolization should be considered selectively in patients who have hepatocellular carcinoma with microvascular invasion. HPB (Oxford). 2019;21:425–433CrossRefGoogle Scholar
  45. 45.
    Wang Z, Ren Z, Chen Y, et al. Adjuvant transarterial chemoembolization for HBV-related hepatocellular carcinoma after resection: a randomized controlled study. Clin Cancer Res. 2018;24(9):2074–2081CrossRefGoogle Scholar
  46. 46.
    Nagasue N, Galizia G, Kohno H, et al. Adverse effects of preoperative hepatic artery chemoembolization for resectable hepatocellular carcinoma: a retrospective comparison of 138 liver resections. Surgery. 1989;106(1):81–86Google Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2019

Authors and Affiliations

  • Chao Li
    • 1
  • Ming-Da Wang
    • 1
  • Lun Lu
    • 2
  • Han Wu
    • 1
  • Jiong-Jie Yu
    • 1
  • Wan-Guang Zhang
    • 3
  • Timothy M. Pawlik
    • 4
  • Yao-Ming Zhang
    • 9
  • Ya-Hao Zhou
    • 5
  • Wei-Min Gu
    • 6
  • Hong Wang
    • 7
  • Ting-Hao Chen
    • 8
  • Jun Han
    • 1
  • Hao Xing
    • 1
  • Zhen-Li Li
    • 1
  • Wan Yee Lau
    • 1
    • 10
  • Meng-Chao Wu
    • 1
  • Feng Shen
    • 1
    Email author
  • Tian Yang
    • 1
    Email author
  1. 1.Department of Hepatobiliary SurgeryEastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University)ShanghaiChina
  2. 2.Department of RadiologyEastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University)ShanghaiChina
  3. 3.Department of Hepatic SurgeryTongji Hospital, Huazhong University of Science and TechnologyWuhanChina
  4. 4.Department of Surgery, Wexner Medical CenterOhio State UniversityColumbusUSA
  5. 5.Department of Hepatobiliary SurgeryPu’er People’s HospitalYunnanChina
  6. 6.The 1st Department of General SurgeryThe Fourth Hospital of HarbinHeilongjiangChina
  7. 7.Department of General SurgeryLiuyang People’s HospitalHunanChina
  8. 8.Department of General SurgeryZiyang First People’s HospitalSichuanChina
  9. 9.The 2nd Department of Hepatobiliary Surgery, Meizhou People’s Hospital (Huangtang Hospital)Meizhou Hospital to Sun Yat-sen UniversityMeizhouChina
  10. 10.Faculty of Medicine the Chinese University of Hong KongPrince of Wales HospitalHong KongChina

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