摘要
背景与目的:近年来,神经浸润在肝内胆管癌(ICC)患者的预后评估及治疗决策支持等方面的临床价值逐渐受到重视。越来越多的证据表明辅助化疗可以改善ICC患者预后,但目前辅助化疗是否能够有效改善ICC合并神经浸润患者总体生存(OS)仍存在一定的争议。因此,本研究探讨ICC神经浸润发生的危险因素并分析辅助化疗对于是否合并神经浸润患者的疗效,以提供临床决策支持。方法:回顾性收集2013年1月—2022年12月于西安交通大学第一附属医院肝胆外科因ICC行意向性根治术的259例患者的临床病理资料,分析ICC患者发生神经浸润的危险因素、影响患者术后预后的危险因素,以及辅助化疗对患者预后的影响。结果:259例患者中,合并神经浸润者占17.7%(46/259)。无神经浸润者中位OS时间为25.0个月,1、3、5年OS率分别为71.3%、38.2%、26.6%;神经浸润者中位OS时间为10.0个月,1、3、5年OS率分别为39.1%、21.4%、0%,两者OS率差异有统计学意义(χ^(2)=8.400,P=0.004)。术前总胆红素水平、CEA水平、CA19-9水平、病毒性肝炎、肝内胆管结石、肝功能Child-Pugh分级、肿瘤位置、肿瘤大小、血管侵犯、N分期、TNM分期与ICC神经浸润发生明显有关(均P<0.05)。CA19-9水平(OR=2.265,95%CI=1.061~4.833)、肝内胆管结石(OR=4.064,95%CI=1.809~9.130)、血管侵犯(OR=3.286,95%CI=1.551~6.964)及N分期(OR=2.365,95%CI=1.149~4.869)是影响ICC神经浸润发生的独立危险因素(均P<0.05)。预后分析显示,CA19-9水平(HR=1.615,95%CI=1.142~2.283)、肝内胆管结石(HR=2.093,95%CI=1.401~3.127)、脉管侵犯(HR=1.563,95%CI=1.032~2.367)、神经浸润(HR=2.120,95%CI=1.392~3.229)、N分期(HR=2.304,95%CI=1.320~4.022)是影响ICC意向性根治术后患者OS的独立危险因素(均P<0.05),辅助化疗是影响ICC术后患者OS的独立保护因素(HR=0.533,95%CI=0.369~0.770,P<0.05)。进一步分析显示,无论在全组ICC患者中或在合并神经浸润的ICC患者中,辅助化疗可以有效延长中位OS时间(均P<0.05),但在无神经浸润ICC患者中,其延长中位OS时间的作用不明显(P>0.05)。结论:CA19-9水平、肝内胆管结石、血管侵犯及N分期与ICC神经浸润的发生密切相关,合并神经浸润的患者术后预后差,但术后辅助化疗可以有效改善该类ICC患者的预后。
Background and Aims:In recent years,the clinical value of perineural invasion for prognosis assessment and treatment decision support in patients with intrahepatic cholangiocarcinoma(ICC)has been increasingly recognized.There is growing evidence that adjuvant chemotherapy can improve the prognosis of ICC patients.However,there remains some controversy regarding whether adjuvant chemotherapy can effectively improve the overall survival(OS)of ICC patients with perineural invasion.Therefore,this study was performed to explore the risk factors for perineural invasion in ICC and analyze the efficacy of adjuvant chemotherapy for patients with concurrent perineural invasion,so as to provide support for clinical decision-making.Methods:The clinicopathologic data of 259 patients who underwent curative-intent resection for ICC in the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to December 2022 were retrospectively collected.The risk factors for perineural invasion in ICC patients,factors influencing postoperative prognosis of patients,and the impact of adjuvant chemotherapy on prognosis were analyzed.Results:Among the 259 patients,17.7%(46/259)had concomitant perineural invasion.The median OS time for patients without perineural invasion was 25.0 months,with 1-,3-,and 5-year overall survival rates of 71.3%,38.2%,and 26.6%,respectively.For patients with perineural invasion,the median OS time was 10.0 months,with 1-,3-,and 5-year overall survival rates of 39.1%,21.4%,and 0.0%,respectively.The difference in survival rates between the two groups was statistically significant(χ^(2)=8.400,P=0.004).The preoperative total bilirubin level,CEA level,CA19-9 level,viral hepatitis,intrahepatic stones,liver function Child-Pugh classification,tumor location,tumor size,vascular invasion,N stage,and TNM stage were significantly associated with perineural invasion in ICC(all P<0.05).CA19-9 level(OR=2.265,95%CI=1.061-4.833),intrahepatic stones(OR=4.064,95%CI=1.809-9.130),vascular invasion(OR=3.286,95%CI=1.551-6.964),and N stage(OR=2.365,95%CI=1.149-4.869)were independent risk factors for perineural invasion in ICC(all P<0.05).Prognostic analysis showed that CA19-9 level(HR=1.615,95%CI=1.142-2.283),intrahepatic bile duct stones(HR=2.093,95%CI=1.401-3.127),vascular invasion(HR=1.563,95%CI=1.032-2.367),perineural invasion(HR=2.120,95%CI=1.392-3.229),and N stage(HR=2.304,95%CI=1.320-4.022)were independent risk factors for OS after curative-intent resection for ICC(all P<0.05),while adjuvant chemotherapy was an independent protective factor for overall survival after ICC surgery(HR=0.533,95%CI=0.369-0.770,P<0.05).Further analysis showed that adjuvant chemotherapy could effectively prolong the median OS time in both the entire group of ICC patients and those with perineural invasion(both P<0.05),but its effect on prolonging median OS time in ICC patients without perineural invasion was not significant(P>0.05).Conclusion:CA19-9 level,intrahepatic stones,vascular invasion,and N stage are closely related to perineural invasion in ICC.Patients with concomitant perineural invasion have poorer postoperative prognosis,but adjuvant chemotherapy can effectively improve the prognosis of such ICC patients.
作者
李起
陈晨
刘恒超
雷建军
张东
耿智敏
LI Qi;CHEN Chen;LIU Hengchao;LEI Jianjun;ZHANG Dong;GENG Zhimin(Department of Hepatobiliary Surgery,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)
出处
《中国普通外科杂志》
CAS
CSCD
北大核心
2024年第2期193-201,共9页
China Journal of General Surgery
基金
国家自然科学基金资助项目(62076194)
陕西省科技厅重点研发计划基金资助项目(2021SF-016
2022SF-606)。
关键词
胆管肿瘤
胆管
肝内
肿瘤浸润
放化疗
辅助
预后
Bile Duct Neoplasms
Bile Ducts,Intrahepatic
Neoplasm Invasiveness
Chemoradiotherapy,Adjuvant
Prognosis
