肝门胆管恶性梗阻患者肝脏有效引流体积对总体生存时间的影响：一项多中心研究

Influence of effective liver drainage volume on overall survival in patients with malignant hilar biliary obstruction: a multicenter study

摘要:

目的 探讨无法手术切除的肝门胆管恶性梗阻患者的肝脏引流体积对其总体生存时间的影响。方法 回顾性分析2002年1月—2019年5月期间在3所内镜中心接受支架引流的633例肝门胆管恶性梗阻（Bismuth Ⅱ-Ⅳ型）患者的临床资料。主要观察指标包括临床成功率、支架通畅期、总体生存时间、有效肝脏引流体积、并发症发生率。结果 肝脏引流体积<30%、30%~50%、>50%患者的临床成功率分别为56.8%（25/44）、77.3%（201/260）和84.2%（277/329）；早期胆管炎发生率分别为31.8%（14/44）、18.8%（49/260）和16.1%（53/329）；中位支架通畅期分别为4.5（95%CI：1.8~7.2）个月、5.6（95%CI：5.0~6.2）个月、6.6（95%CI：5.2~8.0）个月； 总体生存时间分别为2.4（95%CI：1.8~3.0）个月、4.0（95%CI：3.4~4.6）个月和4.9（95%CI：4.4~5.4）个月。30%~50%肝脏引流体积组的临床成功率（χ2=8.28，P=0.012）、中位支架通畅期（χ2=18.87，P=0.015）、总体生存时间（χ2=6.93，P=0.024）均明显高于<30%组。进一步的多因素Cox回归分析显示疾病种类（肝细胞肝癌比肝门胆管癌：HR=1.50，95%CI：1.18~1.91，P=0.001； 胆囊癌比肝门胆管癌：HR=1.45，95%CI：1.14~1.85，P=0.002；转移性胆管肿瘤比肝门胆管癌：HR=1.48，95%CI：1.08~2.04，P=0.015）、胆红素水平>200 μmol/L（HR=1.35，95%CI：1.14~1.60，P<0.001）、金属支架（HR=0.67，95%CI：0.56~0.79，P<0.001）、肝脏引流体积（体积30%~50%比<30%： HR=0.64，95%CI：0.45~0.90，P=0.010； 体积>50%比<30%： HR=0.58，95%CI：0.41~0.81，P=0.002）和抗肿瘤治疗（HR=0.51，95%CI：0.42~0.61，P<0.001）均为总体生存时间的独立预测因素。结论 对无法手术切除的肝门胆管恶性梗阻患者进行内镜支架引流时，至少要达到30%的肝脏体积才能获得更好的总体生存时间。此外，采用金属支架引流并给予其他抗肿瘤治疗亦有助于增加生存获益。

Abstract:

Objective To investigate the influence of liver drainage volume on overall survival time in patients with unresectable malignant hilar bile duct obstruction. Methods Data of 633 patients with unresectable malignant hilar bile duct obstruction (BismuthⅡ-Ⅳ) who underwent endoscopic stent drainage in 3 endoscopy centers from January 2002 to May 2019 were retrospectively analyzed. Main observation indicators included clinical success rate, stent patency, overall survival, the effective liver drainage volume, and complication incidence. Results The clinical success rates of patients with liver drainage volume <30%, 30%-50%, and >50% were 56.8% (25/44), 77.3% (201/260) and 84.2% (277/329) respectively. The incidences of early cholangitis were 31.8% (14/44), 18.8% (49/260) and 16.1% (53/329). The median stent patency time was 4.5 (95%CI: 1.8-7.2) months, 5.6 (95%CI: 5.0-6.2) months and 6.6 (95%CI: 5.2-8.0) months. The overall survival time was 2.4 (95%CI: 1.8-3.0) months, 4.0 (95%CI: 3.4-4.6) months and 4.9 (95%CI:4.4-5.4) months, respectively. The clinical success rate (χ2=8.28, P=0.012), median stent patency period (χ2=18.87, P=0.015) and overall survival time (χ2=6.93, P=0.024) of 30%-50% liver drainage volume group were significantly higher than those of <30% group. Further multivariate cox regression analysis showed that the disease type (hepatocellular carcinoma VS hilar cholangiocarcinoma: HR=1.50, 95%CI:1.18-1.91, P=0.001; gallbladder carcinoma VS hilar cholangiocarcinoma: HR=1.45, 95%CI:1.14-1.85, P=0.002; metastatic cholangiocarcinoma VS hilar cholangiocarcinoma: HR=1.48, 95%CI:1.08-2.04, P=0.015), bilirubin level >200 μmol/L (HR=1.35, 95%CI:1.14-1.60, P<0.001),metal stents (HR=0.67, 95%CI:0.56-0.79, P<0.001), liver drainage volume (volume 30%-50% VS <30%: HR=0.64, 95%CI: 0.45-0.90, P=0.010; volume>50% VS <30%: HR=0.58, 95%CI:0.41-0.81, P=0.002) and anti-tumor therapy (HR=0.51, 95%CI:0.42-0.61, P<0.001) were independent predictors for overall survival time of patients with unresectable malignant hilar bile duct obstruction. Conclusion When endoscopic stent drainage is performed for patients with unresectable malignant hilar bile duct obstruction, at least 30% liver volume is required for better overall survival. In addition, the use of metal stent drainage and anti-tumor therapy may increase survival benefits.