Effectiveness of postoperative transarterial chemoembolization for huge intrahepatic cholangiocarcinoma

Abstract

Abstract:

ObjectiveTo investigate the effect of postoperative transarterial chemoembolization (TACE) for huge intrahepatic cholangiocarcinoma (ICC).MethodsData of 125 huge ICC (diameter ≥10 cm) patients with surgical treatment treated with or without TACE (TACE group 35 cases, and non-TACE group 90 cases) between January 2009 and December 2013 were analyzed retrospectively. Both recurrence rate and overall survival (OS) rate were analyzed using the Kaplan-Meier method and the difference using Log-Rank test. Cox regression analysis was used to explore the independent risk factors of postoperative recurrence and OS. Propensity score matching was used to reduce the difference between groups. Subgroup analysis was done for benefited patients from TACE based on the 8th TNM staging of ICC.ResultsTACE group had similar recurrence and OS with non-TACE group. 5-year recurrence rate and OS rate were 85.7%vs. 84.4%,P=0.487; 22.9%vs. 20.0%,P=0.426, respectively. After 1∶1 propensity score matching with 33 cases each group, there was no significant difference between two groups (P=0.114 for recurrence,P=0.197 for OS). According to TNM sta-ging, there were 61 cases in stage Ⅰ and 64 cases in stage Ⅱ. Staging analysis showed that TACE group and non-TACE groups yielded similar recurrence and OS in patients with stage Ⅰ. However, for patients in stage Ⅱ, TACE group had lower recurrence rate (91.7%vs. 97.5%,P=0.022) and higher OS rate (12.5%vs. 2.5%,P=0.002). After adjustment for multiple tumors, vascular invasion, and CEA ≥5 μg/L, TACE was independent risk factor of recurrence (hazard ratio: 0.564, 95%CI: 0.327-0.974) and OS (hazard ratio: 0.449, 95%CI: 0.259-0.777) in patients with stage Ⅱ.ConclusionsFor patients with huge ICC, postoperative TACE may improve the prognosis of patients with TNM stage Ⅱ.

Key words:Huge intrahepatic cholangiocarcinoma,Transarterial chemoembolization,Long-term prognosis,TNM staging

CLC Number:

R735.8

SI Anfeng, LEI Zhengqing, YANG Pinghua, JIANG Tao, WANG Xuan, CHENG Zhangjun. Effectiveness of postoperative transarterial chemoembolization for huge intrahepatic cholangiocarcinoma[J]. Journal of Surgery Concepts & Practice, 2021, 26(02): 138-143.

Figures/Tables7

变量	TACE组（n=35）	非TACE组（n=90）	P值
年龄（岁）	54 (47~64)	55 (46~62)	0.835
男性	21 (60.0)	52 (57.8)	0.821
有结石	5 (14.3)	18 (20.0)	0.459
乙肝表面抗原阳性	17 (48.6)	38 (42.2)	0.521
甲胎蛋白≥20 μg/L	11 (31.4)	18 (20.0)	0.174
糖类抗原19-9≥39 U/L	15 (42.9)	45 (50.0)	0.473
癌胚抗原≥5 μg/L	5 (14.3)	25 (27.8)	0.113
总胆红素≥17.1 μmol/L	3 (8.6)	17 (18.9)	0.254
丙氨酸转氨酶≥44 U/L	6 (17.1)	13 (14.4)	0.706
碱性磷酸酶≥129 U/L	10 (28.6)	34 (37.8)	0.333
肿瘤直径（cm）	11.1 (10.4~13.3)	11.7 (10.4~13.0)	0.839
肿瘤数目
多发	17 (48.6)	34 (37.8)	0.270
单发	18 (51.4)	56 (62.2)
肝硬化	9 (25.7)	20 (22.2)	0.678
术中输血	14 (40.0)	26 (28.9)	0.232
分化差	2 (5.7)	5 (5.6)	1.000
血管侵犯	11 (31.4)	14 (15.6)	0.046
TNM分期
Ⅰ: T_1bN₀M₀	11 (31.4)	50 (55.6)	0.015
Ⅱ: T₂N₀M₀	24 (68.6)	40 (44.4)

变量	单因素		多因素
变量	风险比（95% CI）	P值	风险比（95% CI）	P值
年龄（岁）55>比≤55	0.950 (0.646~1.397)	0.794
男比女	0.973 (0.659~1.439)	0.893
结石	1.023 (0.628~1.667)	0.927
乙肝表面抗原阳性	1.053 (0.714~1.552)	0.795
甲胎蛋白（μg/L）>20比≤20	1.297 (0.835~2.013)	0.247
糖类抗原19-9（U/L）>39比≤39	1.372 (0.931~2.022)	0.110
癌胚抗原（μg/L）>5比≤5	2.346 (1.518~3.627)	<0.001	1.804 (1.142~2.850)	0.011
总胆红素（μmol/L）>17.1比≤17.1	1.101 (0.654~1.852)	0.718
丙氨酸转氨酶（U/L）>44比≤44	0.977 (0.573~1.666)	0.931
碱性磷酸酶（U/L）>129比≤129	1.187 (0.794~1.774)	0.404
肿瘤多发	2.212 (1.490~3.284)	<0.001	1.857 (1.229~2.807)	0.003
肝硬化	1.001 (0.634~1.580)	0.998
术中输血	1.299 (0.861~1.959)	0.212
分化差	1.451 (0.635~3.317)	0.377
血管侵犯	1.871 (1.181~2.964)	0.008	1.871 (1.164~3.007)	0.010
TACE	0.840 (0.547~1.291)	0.427

变量	单因素		多因素
变量	风险比（95%CI）	P值	风险比（95%CI）	P值
年龄（岁）55>比≤55	0.893 (0.612~1.301)	0.555
男比女	1.082 (0.738~1.585)	0.687
结石	0.804 (0.495~1.307)	0.380
乙肝表面抗原阳性	1.158 (0.794~1.687)	0.446
甲胎蛋白（μg/L）>20比≤20	1.762 (1.138~2.729)	0.011
糖类抗原19-9（U/L）>39比≤39	1.210 (0.832~1.759)	0.319
癌胚抗原（μg/L）>5比≤5	1.555 (1.015~2.382)	0.042
总胆红素（μmol/L）>17.1比≤17.1	0.866 (0.509~1.473)	0.596
丙氨酸转氨酶（U/L）>44比≤44	1.131 (0.682~1.877)	0.633
碱性磷酸酶（U/L）>129比≤129	1.268 (0.585~1.876)	0.234
肿瘤多发	1.927 (1.315~2.826)	0.001	1.885 (1.285~2.765)	0.001
肝硬化	0.943 (0.594~1.498)	0.805
术中输血	1.297 (0.872~1.930)	0.199
分化差	1.330 (0.583~3.034)	0.498
血管侵犯	2.536 (1.600~4.020)	<0.001	2.748 (1.711~4.412)	<0.001
TACE	0.862 (0.566~1.312)	0.488

变量	TACE组（n=33）	非TACE组（n=33）	P值
年龄（岁）	54.0 (46.5~64.5)	56.0 (46.5~62.5)	0.768
男性	19 (57.6)	19 (57.6)	1.000
有结石	5 (15.2)	4 (12.1)	1.000
乙肝表面抗原阳性	15 (45.5)	17 (51.5)	0.622
甲胎蛋白≥20 μg/L	9 (27.3)	8 (24.2)	0.778
糖类抗原19-9≥39 U/L	13 (39.4)	16 (48.5)	0.457
癌胚抗原≥5 μg/L	5 (15.2)	3 (9.1)	0.706
总胆红素≥17.1 μmol/L	3 (9.1)	2 (6.1)	/
丙氨酸转氨酶≥44 U/L	5 (15.2)	6 (18.2)	0.741
碱性磷酸酶≥129 U/L	9 (27.3)	11 (33.3)	0.592
肿瘤直径（cm）	11.1 (10.5~13.5)	11.5 (10.3~12.3)	0.620
肿瘤数目
多发	16 (48.5)	14 (42.4)	0.621
单发	17 (51.5)	19 (57.6)
肝硬化	7 (21.2)	6 (18.2)	0.757
术中输血	13 (39.4)	7 (21.2)	0.108
分化差	2 (6.1)	2 (6.1)	/
血管侵犯	9 (27.3)	7 (21.2)	0.566
TNM分期
Ⅰ: T_1bN₀M₀	11 (33.3)	14 (42.2)	0.447
Ⅱ: T₂N₀M₀	22 (66.7)	19 (57.6)

References19

[1]	Aljiffry M, Abdulelah A, Walsh M, et al. Evidence-based approach to cholangiocarcinoma: a systematic review of the current literature[J]. J Am Coll Surg, 2009, 208(1):134-147.
[2]	Wang Y, Li J, Xia Y, et al. Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy[J]. J Clin Oncol, 2013, 31(9):1188-1195.
[3]	Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma[J]. J Hepatol, 2014, 60(6):1268-1289. doi:10.1016/j.jhep.2014.01.021pmid:24681130
[4]	Shen WF, Zhong W, Liu Q, et al. Adjuvant transcatheter arterial chemoembolization for intrahepatic cholangiocarcinoma after curative surgery: retrospective control study[J]. World J Surg, 2011, 35(9):2083-2091. doi:10.1007/s00268-011-1171-ypmid:21698503
[5]	Wu ZF, Zhang HB, Yang N, et al. Postoperative adjuvant transcatheter arterial chemoembolisation improves survival of intrahepatic cholangiocarcinoma patients with poor prognostic factors: results of a large monocentric series[J]. Eur J Surg Oncol, 2012, 38(7):602-610. doi:10.1016/j.ejso.2012.02.185pmid:22417704
[6]	Li T, Qin LX, Zhou J, et al. Staging, prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma after curative resection[J]. Liver Int, 2014, 34(6):953-960.
[7]	Jeong S, Zheng B, Wang J, et al. Transarterial chemoembolization: a favorable postoperative management to improve prognosis of hepatitis B virus-associated intrahe-patic cholangiocarcinoma after surgical resection[J]. Int J Biol Sci, 2017, 13(10):1234-1241.
[8]	Lu Z, Liu S, Yi Y, et al. Serum gamma-glutamyl transferase levels affect the prognosis of patients with intrahepatic cholangiocarcinoma who receive postoperative adjuvant transcatheter arterial chemoembolization: a propensity score matching study[J]. Int J Surg, 2017, 37:24-28.
[9]	Li J, Wang Q, Lei Z, et al. Adjuvant transarterial chemoembolization following liver resection for intrahe-patic cholangiocarcinoma based on survival risk stratifica-tion[J]. Oncologist, 2015, 20(6):640-647.
[10]	Wang L, Deng M, Ke Q, et al. Postoperative adjuvant therapy following radical resection for intrahepatic cholangiocarcinoma: a multicenter retrospective study[J]. Cancer Med, 2020, 9(8):2674-2685.
[11]	Austin PC. Some methods of propensity-score matching had superior performance to others: results of an empirical investigation and Monte Carlo simulations[J]. Biom J, 2009, 51(1):171-184. doi:10.1002/bimj.200810488pmid:19197955
[12]	Mazzaferro V, Gorgen A, Roayaie S, et al. Liver resection and transplantation for intrahepatic cholangiocarcinoma[J]. J Hepatol, 2020, 72(2):364-377. doi:S0168-8278(19)30711-1pmid:31954498
[13]	Spolverato G, Kim Y, Alexandrescu S, et al. Is hepatic resection for large or multifocal intrahepatic cholangiocarcinoma justified? results from a multi-institutional colla-boration[J]. Ann Surg Oncol, 2015, 22(7):2218-2225. doi:10.1245/s10434-014-4223-3pmid:25354576
[14]	Hyder O, Marques H, Pulitano C, et al. A nomogram to predict long-term survival after resection for intrahepatic cholangiocarcinoma: an Eastern and Western experience[J]. JAMA Surg, 2014, 149(5):432-438. pmid:24599477
[15]	Sapisochin G, Facciuto M, Rubbia-Brandt L, et al. Liver transplantation for “very early” intrahepatic cholangiocarcinoma: international retrospective study supporting a prospective assessment[J]. Hepatology, 2016, 64(4):1178-1188. doi:10.1002/hep.28744pmid:27481548
[16]	Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives[J]. Gut, 2014, 63(5):844-855.
[17]	Wang Z, Ren Z, Chen Y, et al. Adjuvant transarterial chemoembolization for HBV-related hepatocellular carcinoma after resection: a randomized controlled study[J]. Clin Cancer Res, 2018, 24(9):2074-2081.
[18]	Wang H, Du PC, Wu MC, et al. Postoperative adjuvant transarterial chemoembolization for multinodular hepatocellular carcinoma within the Barcelona Clinic Liver Cancer early stage and microvascular invasion[J]. Hepatobiliary Surg Nutr, 2018, 7(6):418-428.
[19]	Ke Q, Lin N, Deng M, et al. The effect of adjuvant therapy for patients with intrahepatic cholangiocarcinoma after surgical resection: a systematic review and meta-analysis[J]. PLoS One, 2020, 15(2):e0229292.