金属支架不同放置位置在肝门胆管恶性梗阻内镜引流术中应用价值的多中心研究

Application value of different metal stents placement position in endoscopic drainage of malig-nant hilar bile duct obstruction:a multicenter study

目的探讨金属支架不同放置位置在肝门胆管恶性梗阻内镜引流术中的应用价值。方法采用回顾性队列研究方法。收集2012年1月至2019年1月3家医学中心收治的300例(海军军医大学第三附属医院216例、空军军医大学西京医院48例、上海交通大学附属第一人民医院36例)肝门胆管恶性梗阻患者的临床病理资料;男164例,女136例;年龄为(67±12)岁。所有患者经多学科联合会诊确定为无法手术切除,行内镜逆行胰胆管造影。观察指标:(1)患者临床病理特征。(2)随访情况。(3)影响患者胆管金属支架通畅时间和总生存时间的相关因素分析。采用门诊、电话等方式进行随访,了解患者胆管金属支架通畅情况和生存情况。随访时间截至2019年7月或患者死亡。正态分布的计量资料以x±s表示,组间比较采用独立样本t检验;偏态分布的计量资料以M(Q 1,Q 3)表示,组间比较采用Mann‑Whitney U检验。计数资料以绝对数或百分比表示,组间比较采用χ²检验或Fisher确切概率法。等级资料比较采用秩和检验。采用Kaplan‑Meier法绘制生存曲线并计算生存率,采用Log‑Rank检验进行生存情况分析。单因素和多因素分析采用COX回归模型,将单因素分析中P<0.1的因素纳入多因素分析。结果(1)患者临床病理特征。300例患者中,163例行内镜引流术中≥1根胆管金属支架的远端跨越十二指肠主乳头(以下简称跨越乳头);137例行内镜引流术中没有胆管金属支架的远端跨越十二指肠主乳头(以下简称未跨越乳头)。跨越乳头患者的年龄,疾病类型(肝门部胆管癌、肝细胞癌、肝内胆管细胞癌、胆囊癌、转移性胆管肿瘤),胆管金属支架类型(单侧金属支架、双侧金属支架)分别为(68±13)岁,95、8、11、31、18例,63、100例;未跨越乳头患者上述指标分别为(64±12)岁,63、22、20、23、9例,126、11例;两者上述指标比较,差异均有统计学意义(t=2.70,χ^(2)=17.69、90.79,P<0.05)。(2)随访情况。300例患者均获得随访,随访时间为5.4(3.1,9.3)个月。跨越乳头和未跨越乳头患者的胆管金属支架通畅时间分别为9.0(8.2,9.8)个月和6.4(4.8,8.0)个月,两者比较,差异有统计学意义(χ^(2)=8.23,P<0.05)。跨越乳头和未跨越乳头患者的总生存时间分别为5.5(4.2,6.8)个月和5.5(4.3,6.8)个月,两者比较,差异无统计学意义(χ^(2)=0.28,P>0.05)。(3)影响患者胆管金属支架通畅时间和总生存时间的相关因素分析。单因素分析结果显示:胆管金属支架类型、胆管金属支架放置位置是影响患者胆管金属支架通畅时间的相关因素(风险比=0.44,0.60,95%可信区间为0.30~0.64,0.42~0.85,P<0.05)。多因素分析结果显示:双侧金属支架是患者胆管金属支架通畅时间的独立保护因素(风险比=0.46,95%可信区间为0.29~0.72,P<0.05)。单因素分析结果显示:疾病类型(肝内胆管细胞癌比肝门部胆管癌)、术前血清总胆红素、胆管金属支架类型、抗肿瘤治疗是影响患者总生存时间的相关因素(风险比=1.05,1.43,0.72,0.61,95%可信区间为0.70~1.57,1.12~1.83,0.55~0.92,0.47~0.81,P<0.05)。多因素分析结果显示:年龄>60岁、疾病类型(肝细胞癌)、术前血清总胆红素>200μmol/L是患者总生存时间的独立危险因素(风险比=1.35,1.98,1.46,95%可信区间为1.02~1.79,1.40~2.80,1.13~1.89,P<0.05);双侧胆管金属支架、接受抗肿瘤治疗是患者总生存时间的独立保护因素(风险比=0.68,0.60,95%可信区间为0.53~0.89,0.45~0.80,P<0.05)。结论肝门胆管恶性梗阻患者在内镜引流术中胆管金属支架是否跨越十二指肠主乳头均安全、可行。双侧胆管金属支架是患者金属支架通畅时间的独立保护因素;年龄>60岁、疾病类型(肝细胞癌)、术前血清总胆红素>200μmol/L是患者内镜引流术后总生存时间的独立危险因素;双侧胆管金属支架、接受抗肿瘤治疗是患者内镜引流术后总生存时间的独立保护因素。

Objective To investigate the application value of different metal stents place-ment position in endoscopic drainage of magnant hilar bile duct obstruction.Methods The retro-spective cohort study was conducted.The clinicopathological data of 300 patients with malignant hilar bile duct obstruction who were admitted to 3 medical centers,including 216 patients in the Third Affiliated Hospital of Naval Medical University,48 patients in the Xijing Hospital of Air Force Medical University,36 patients in the First People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine,from January 2012 to January 2019 were collected.There were 164 males and 136 females,aged(67±12)years.All patients were determined to be unresectable by multidisciplinary consultation and underwent endoscopic retrograde cholangiopancreatography.Observation indicators:(1)clinicopathological features of patients;(2)follow-up;(3)analysis of influencing factors for patency time of metal biliary stents and overall survival time of patients.Follow-up was conducted using outpatient examination and telephone interview to detect patency of metal biliary stents and survival of patients up to July 2019 or death of patients.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was conducted using the independent sample t test.Measurement data with skewed distribution were represented as M(Q 1,Q 3),and comparison between groupwas conducted using the Mann-Whitney U test.Count data were expressed as absolute numbers or percentages,and comparison between groups was conducted using the chi-square test or Fisher exact probability.Comparison of ordinal data was conducted using the rank sum test.Kaplan-Meier method was used to calculate survival rates and draw survival curves,and Log-Rank test was used to conduct survival analysis.COX regression model was used for univariate and multivariate analyses.Factors with P<0.1 in univariate analysis were included in multivariate analysis.Results(1)Clinicopathological features of patients.Of the 300 patients,163 cases underwent endoscopic drainage with at least one metal biliary stent'distal portion crossing the duodenal main papilla(hereinafter referred to as crossing papilla),and 137 cases underwent endoscopic drainage with no metal biliary stent'distal portion crossing the duodenal main papilla(hereinafter referred to as no crossing papilla).Age,disease type(hilar cholangiocarcinoma,hepatocellular carcinoma,intrahepatic cholangio-carcinoma,gallbladder carcinoma,metastatic cholangiocarcinoma),metal biliary stents type(unilateral metal biliary stent,bilateral metal biliary stents)of patients with crossing papilla were(68±13)years,95,8,11,31,18,63,100,respectively.The above indicators of patients with no crossing papilla were(64±12)years,63,22,20,23,9,126,11,respectively.There were significant differences in the above indicators between patients with crossing papilla and patients with no crossing papilla(t=2.70,χ^(2)=17.69,90.79,P<0.05).(2)Follow-up.All the 300 patients were followed up for 5.4(3.1,9.3)months.The patency time of metal biliary stents was 9.0(8.2,9.8)months and 6.4(4.8,8.0)months of patients with crossing papilla and patients with no crossing papilla,showing a significant difference between them(χ^(2)=8.23,P<0.05).The overall survival time was 5.5(4.2,6.8)months and 5.5(4.3,6.8)months of patients with crossing papilla and patients with no crossing papilla,showing no significant difference between them(χ^(2)=0.28,P>0.05).(3)Analysis of influencing factors for patency time of metal biliary stents and overall survival time of patients.Results of univariate analysis showed that type of metal biliary stents and the placement position of metal biliary stents were related factors affecting the patency time of metal biliary stents[hazard ratio(HR)=0.44,0.60,95% confidence intervals as 0.30‒0.64,0.42‒0.85,P<0.05].Results of multi-variate analysis showed that bilateral metal biliary stents was an independent protective factor for the patency time of metal biliary stents(HR=0.46,95% confidence interval as 0.29‒0.72,P<0.05).Results of univariate analysis showed that disease type(intrahepatic cholangiocarcinoma versus hilar cholangiocarcinoma),preoperative serum totl bilirubin,type of metal biliary stents,anti-tumor therapy were related factors affecting the overall survival time of patients(HR=1.05,1.43,0.72,0.61,95% confidence intervals as 0.70‒1.57,1.12‒1.83,0.55‒0.92,0.47‒0.81,P<0.05).Results of multi-variate anlysis showed that age>60 years,disease type as hepatocellular carcinoma,preoperative serum total bilirubin>200μmol/L were independent risk factors for the overall survival time of patients(HR=1.35,1.98,1.46,95%confidence intervals as 1.02‒1.79,1.40‒2.80,1.13‒1.89,P<0.05),and bilateral metal biliary stents,anti-tumor therapy were independent protective factors for the overall survival time of patients(HR=0.68,0.60,95%confidence intervals as 0.53‒0.89,0.45‒0.80,P<0.05).Conclusions Endoscopic drainage with or without metal biliary stents'distal portion crossing the duodenal main papilla is safe nd feasible for patients with malignant hilar bile duct obstruction.Bilateral metal biliary stents is an independent protective factor for the patency time of metal biliary stents.Age>60 years,disease type as hepatocellular carcinoma,preoperative serum total bilirubin>200μmol/L are independent risk factors for the overall survival time of patients,and bilateral metal biliary stents,anti-tumor therapy are independent protective factors for the overall survival time of patients.