术后辅助化疗对可切除胆道恶性肿瘤的疗效分析

doi:10.3877/cma.j.issn.2095-3232.2022.04.013

目的

探讨术后辅助化疗对可切除胆道恶性肿瘤（BTC）的疗效。

方法

回顾性分析2017年1月至2019年11月在海军军医大学附属东方肝胆外科医院行手术治疗的151例BTC患者临床资料。其中男84例，女67例；平均年龄（58±6）岁。患者均签署知情同意书，符合医学伦理学规定。根据术后是否采用辅助化疗，将患者分为化疗组（104例）和非化疗组（47例）；根据化疗方案是否含吉西他滨（G），化疗组进一步分为含G方案组（89例）和非含G方案组（15例）。分析术后辅助化疗及不同化疗方案对患者无复发生存期（RFS）的影响。生存分析采用Kaplan-Meier法和Tarone-Ware检验。采用Cox比例风险回归模型分析患者术后RFS的影响因素。

结果

随访时间6~24个月，中位时间15个月。化疗组中位RFS为13个月，非化疗组6个月，术后辅助化疗可明显改善患者的RFS（χ²=13.286，P<0.05）。Cox回归分析显示，术后CA19-9降至正常是RFS的保护因素（HR=0.375，95%CI：0.204~0.691，P<0.05），而化疗方案对RFS无影响（HR=1.603，95%CI：0.706~3.636，P>0.05）。

结论

术后辅助化疗可延缓可切除BTC复发，改善患者生存预后，而化疗方案对复发并无影响。术后CA19-9未降至正常是可切除BTC复发的独立危险因素，对此类患者应加强随访。

关键词: 胆管肿瘤, 化学治疗, 预后, 吉西他滨

Objective

To evaluate the efficacy of postoperative adjuvant chemotherapy for resectable biliary tract cancer (BTC).

Methods

Clinical data of 151 patients with BTC who underwent surgery in Eastern Hepatobiliary Surgery Hospital affiliated to Naval Medical University from January 2017 to November 2019 were retrospectively analyzed. Among them, 84 patients were male and 67 female, aged (58±6) years on average. The informed consents of all patients were obtained and the local ethical committee approval was received. According to whether postoperative adjuvant chemotherapy was delivered, all patients were divided into the chemotherapy group (n=104) and non-chemotherapy group (n=47). According to whether chemotherapy regimen contained gemcitabine (G), patients in the chemotherapy group were further divided into G-containing regimen (n=89) and G-free regimen subgroups (n=15). The impact of postoperative adjuvant chemotherapy and different chemotherapy regimens on the recurrence-free survival (RFS) was assessed. Survival analysis was conducted by Kaplan-Meier method and Tarone-Ware test. The influencing factors of postoperative RFS were analyzed by Cox proportional hazards regression model.

Results

The follow-up duration was ranged from 6 to 24 months, with a median of 15 months. The median RFS was 13 months in the chemotherapy group and 6 months in the non-chemotherapy group. Postoperative adjuvant chemotherapy significantly improved the RFS of patients (χ²=13.286, P<0.05). Cox regression analysis showed that decline of postoperative CA19-9 to normal range was a protective factor of RFS (HR=0.375, 95%CI: 0.204-0.691, P<0.05), whereas chemotherapy regimen exerted no effect on RFS (HR=1.603, 95%CI: 0.706-3.636, P>0.05).

Conclusions

Postoperative adjuvant chemotherapy can prevent recurrence and improve the survival of resectable BTC patients. Nevertheless, chemotherapy regimen exerts no effect upon the recurrence. The failure of postoperative CA19-9 decline to normal range is an independent risk factor for the recurrence of resectable BTC. Postoperative follow-up should be strengthened for these patients.

Key words: Bile duct neoplasms, Chemotherapy, Prognosis, Gemcitabine

表1 化疗组与非化疗组胆道恶性肿瘤患者一般情况比较

指标		化疗组	非化疗组	统计值	P值
年龄(岁)		57±9	58±8	t=0.920	0.339
男性(例)		60	24	χ²=0.576	0.448
肿瘤部位(例)				χ²=2.877	0.411
	肝内胆管癌	41	15
	肝门部胆管癌	14	4
	远端胆管癌	11	9
	胆囊癌	38	19
肿瘤分期(例)				χ²=3.999	0.406
	Ⅰ期	15	8
	Ⅱ期	31	12
	Ⅲ期	38	12
	Ⅳ期	20	15
肿瘤分化程度(例)				χ²=1.807	0.405
	低分化	12	7
	中-低分化	17	4
	中分化	75	36
手术切缘阴性(例)		92	40	χ²=0.331	0.565
淋巴结转移(例)		48	22	χ²=0.006	0.940

表1 化疗组与非化疗组胆道恶性肿瘤患者一般情况比较

指标		化疗组	非化疗组	统计值	P值
年龄(岁)		57±9	58±8	t=0.920	0.339
男性(例)		60	24	χ²=0.576	0.448
肿瘤部位(例)				χ²=2.877	0.411
	肝内胆管癌	41	15
	肝门部胆管癌	14	4
	远端胆管癌	11	9
	胆囊癌	38	19
肿瘤分期(例)				χ²=3.999	0.406
	Ⅰ期	15	8
	Ⅱ期	31	12
	Ⅲ期	38	12
	Ⅳ期	20	15
肿瘤分化程度(例)				χ²=1.807	0.405
	低分化	12	7
	中-低分化	17	4
	中分化	75	36
手术切缘阴性(例)		92	40	χ²=0.331	0.565
淋巴结转移(例)		48	22	χ²=0.006	0.940

图1 术后辅助化疗对可切除胆道恶性肿瘤患者无复发生存影响的Kaplan-Meier曲线

表2 不同因素对胆道恶性肿瘤患者术后RFS影响的Cox回归分析

因素	b	SE(b)	Wald χ²	HR	95%CI	P
CA19-9正常^a	-0.981	0.311	9.910	0.375	0.204~0.691	0.002
性别（男）	-0.164	0.274	0.358	0.849	0.496~1.452	0.550
年龄＜55岁	-0.160	0.273	0.343	0.852	0.500~1.454	0.558
肿瘤分期（Ⅳ期）	0.186	0.169	1.206	1.205	0.864~1.679	0.272
分化程度（中低分化）	0.196	0.186	1.113	1.217	0.845~1.753	0.291
淋巴结转移	0.305	0.297	1.055	1.357	0.758~2.430	0.304
切缘阴性	0.532	0.405	1.726	1.702	0.770~3.764	0.189
化疗方案（含G）	0.472	0.418	1.274	1.603	0.706~3.636	0.259

表2 不同因素对胆道恶性肿瘤患者术后RFS影响的Cox回归分析

因素	b	SE(b)	Wald χ²	HR	95%CI	P
CA19-9正常^a	-0.981	0.311	9.910	0.375	0.204~0.691	0.002
性别（男）	-0.164	0.274	0.358	0.849	0.496~1.452	0.550
年龄＜55岁	-0.160	0.273	0.343	0.852	0.500~1.454	0.558
肿瘤分期（Ⅳ期）	0.186	0.169	1.206	1.205	0.864~1.679	0.272
分化程度（中低分化）	0.196	0.186	1.113	1.217	0.845~1.753	0.291
淋巴结转移	0.305	0.297	1.055	1.357	0.758~2.430	0.304
切缘阴性	0.532	0.405	1.726	1.702	0.770~3.764	0.189
化疗方案（含G）	0.472	0.418	1.274	1.603	0.706~3.636	0.259

[1]	Komaya K, Ebata T, Shirai K, et al. Recurrence after resection with curative intent for distal cholangiocarcinoma[J]. Br J Surg, 2017, 104(4):426-433.
[2]	Wirasorn K, Ngamprasertchai T, Khuntikeo N, et al. Adjuvant chemotherapy in resectable cholangiocarcinoma patients[J]. J Gastroenterol Hepatol, 2013, 28(12):1885-1891.
[3]	Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer[J]. N Engl J Med, 2010, 362(14):1273-1281.
[4]	Sasaki T, Isayama H, Nakai Y, et al. Multicenter phaseⅡstudy of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine[J]. Invest New Drugs, 2012, 30(2):708-713.
[5]	Kobayashi S, Ueno M, Ohkawa S, et al. A retrospective study of S-1 monotherapy as second-line treatment for patients with advanced biliary tract cancer[J]. Jpn J Clin Oncol, 2012, 42(9):800-806.
[6]	Primrose JN, Fox RP, Palmer DH, et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study[J]. Lancet Oncol, 2019, 20(5):663-673.
[7]	Malka D, Edeline J. Adjuvant capecitabine in biliary tract cancer: a standard option?[J]. Lancet Oncol, 2019, 20(5):606-608.
[8]	Rizzo1 A, Brandi G. Adjuvant systemic treatment in resected biliary tract cancer: state of the art, controversies, and future directions[J]. Cancer Treat Res Commun, 2021(27):100334.
[9]	Nara S, Esaki M, Ban D, et al. Adjuvant and neoadjuvant therapy for biliary tract cancer: a review of clinical trials[J]. Jpn J Clin Oncol, 2020, 50(12):1353-1363.
[10]	Akhoundova Sanoyan D, McNamara MG, Lamarca A, et al. Adjuvant chemotherapy in biliary tract cancer: state of the art and future perspectives[J]. Curr Opin Oncol, 2020, 32(4):364-369.
[11]	Edeline J, Benabdelghani M, Bertaut A, et al. Gemcitabine and oxaliplatin chemotherapy or surveillance in resected biliary tract cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): a randomized phase Ⅲ study[J]. J Clin Oncol, 2019, 37(8):658-667.
[12]	Ebata T, Hirano S, Konishi M, et al. Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer[J]. Br J Surg, 2018, 105(3):192-202.
[13]	Kainuma O, Miura F, Furukawa D, et al. Feasibility and efficacy of gemcitabine plus cisplatin combination therapy after curative resection for biliary tract cancer[J]. J Hepatobiliary Pancreat Sci, 2015, 22(11):789-794.
[14]	Siebenhüner AR, Seifert H, Bachmann H, et al. Adjuvant treatment of resectable biliary tract cancer with cisplatin plus gemcitabine: a prospective single center phase Ⅱ study[J]. BMC Cancer, 2018, 18(1):72.
[15]	Luvira V, Satitkarnmanee E, Pugkhem A, et al. Postoperative adjuvant chemotherapy for resectable cholangiocarcinoma[J]. Cochrane Database Syst Rev, 2021, 9(9):CD012814.
[16]	Mizuno T, Ebata T, Yokoyama Y, et al. Adjuvant gemcitabine monotherapy for resectable perihilar cholangiocarcinoma with lymph node involvement: a propensity score matching analysis[J]. Surg Today, 2017, 47(2):182-192.
[17]	Fujiwara Y, Kobayashi S, Nagano H, et al. Pharmacokinetic study of adjuvant gemcitabine therapy for biliary tract cancer following major hepatectomy (KHBO1101)[J]. PLoS One, 2015, 10(12):e0143072.
[18]	Sur MD, In H, Sharpe SM, et al. Defining the benefit of adjuvant therapy following resection for intrahepatic cholangiocarcinoma[J]. Ann Surg Oncol, 2015, 22(7):2209-2217.
[19]	Reames BN, Bagante F, Ejaz A, et al. Impact of adjuvant chemotherapy on survival in patients with intrahepatic cholangiocarcinoma: a multi-institutional analysis[J]. HPB, 2017, 19(10):901-909.
[20]	Chen X, Meng F, Xiong H, et al. Adjuvant therapy for resectable biliary tract cancer: a Bayesian network analysis[J]. Front Oncol, 2021(11):600027.
[21]	Yoo C, Shin SH, Park JO, et al. Current status and future perspectives of perioperative therapy for resectable biliary tract cancer:a multidisciplinary review[J]. Cancers, 2021, 13(7):1647.
[22]	Geng ZM, Cai ZQ, Zhang Z, et al. Estimating survival benefit of adjuvant therapy based on a Bayesian network prediction model in curatively resected advanced gallbladder adenocarcinoma[J]. World J Gastroenterol, 2019, 25(37):5655-5666.

[1]	应康, 杨璨莹, 刘凤珍, 陈丽丽, 刘燕娜. 左心室心肌应变对无症状重度主动脉瓣狭窄患者的预后评估价值[J]. 中华医学超声杂志（电子版）, 2023, 20(06): 581-587.
[2]	衣晓丽, 胡沙沙, 张彦. HER-2低表达对乳腺癌新辅助治疗疗效及预后的影响[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 340-346.
[3]	施杰, 李云涛, 高海燕. 腋窝淋巴结阳性Luminal A型乳腺癌患者新辅助与辅助化疗的预后及影响因素分析[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 353-361.
[4]	谭巧, 苏小涵, 侯令密, 黎君彦, 邓世山. 乳腺髓样癌的诊治进展[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 366-368.
[5]	杨倩, 李翠芳, 张婉秋. 原发性肝癌自发性破裂出血急诊TACE术后的近远期预后及影响因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 33-36.
[6]	栗艳松, 冯会敏, 刘明超, 刘泽鹏, 姜秋霞. STIP1在三阴性乳腺癌组织中的表达及临床意义研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 52-56.
[7]	马伟强, 马斌林, 吴中语, 张莹. microRNA在三阴性乳腺癌进展中发挥的作用[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 111-114.
[8]	江振剑, 蒋明, 黄大莉. TK1、Ki67蛋白在分化型甲状腺癌组织中的表达及预后价值研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 623-626.
[9]	晏晴艳, 雍晓梅, 罗洪, 杜敏. 成都地区老年转移性乳腺癌的预后及生存因素研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 636-638.
[10]	鲁鑫, 许佳怡, 刘洋, 杨琴, 鞠雯雯, 徐缨龙. 早期LC术与PTCD续贯LC术治疗急性胆囊炎对患者肝功能及预后的影响比较[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 648-650.
[11]	姜明, 罗锐, 龙成超. 闭孔疝的诊断与治疗：10年73例患者诊疗经验总结[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 706-710.
[12]	卢艳军, 马健, 白鹏宇, 郭凌宏, 刘海义, 江波, 白文启, 张毅勋. 纳米碳在腹腔镜直肠癌根治术中253组淋巴结清扫的临床效果[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 473-477.
[13]	李永胜, 孙家和, 郭书伟, 卢义康, 刘洪洲. 高龄结直肠癌患者根治术后短期并发症及其影响因素[J]. 中华临床医师杂志(电子版), 2023, 17(9): 962-967.
[14]	王军, 刘鲲鹏, 姚兰, 张华, 魏越, 索利斌, 陈骏, 苗成利, 罗成华. 腹膜后肿瘤切除术中大量输血患者的麻醉管理特点与分析[J]. 中华临床医师杂志(电子版), 2023, 17(08): 844-849.
[15]	索利斌, 刘鲲鹏, 姚兰, 张华, 魏越, 王军, 陈骏, 苗成利, 罗成华. 原发性腹膜后副神经节瘤切除术麻醉管理的特点和分析[J]. 中华临床医师杂志(电子版), 2023, 17(07): 771-776.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Efficacy analysis of postoperative adjuvant chemotherapy for resectable biliary tract cancer

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Efficacy analysis of postoperative adjuvant chemotherapy for resectable biliary tract cancer