肝门部胆管癌外科治疗的预后影响因素分析

Analysis of prognostic factors in the surgical treatment of hilar cholangiocarcinoma

  • 摘要:  目的探讨肝门部胆管癌外科治疗的预后影响因素。方法采用回顾性病例对照研究方法。收集2010年1月至2017年12月北部战区总医院收治的93例行外科治疗肝门部胆管癌患者的临床病理资料;男61例,女32例;年龄为(64±8)岁,年龄范围为43~84岁。根据肝门部胆管癌不同术前分型及术中探查情况施行相应手术。观察指标:(1)手术治疗情况。(2)肿瘤分型和分期以及分化程度:①肿瘤分型和分期;②肿瘤分化程度。(3)随访情况。(4)预后影响因素分析:①单因素分析;②多因素分析。(5)亚组分析。采用门诊和电话方式进行随访,随访内容为患者生存时间和生存率。随访时间截至2017年12月31日。采用Kaplan-Meier法计算生存时间及生存率,并绘制生存曲线;采用Log-rank检验进行生存情况分析。单因素分析采用Log-rank检验,多因素分析采用COX比例风险模型。结果(1)手术治疗情况:93例患者均行手术治疗,其中51例行根治性切除术;23例行姑息性切除术;16例行胆管内引流或外引流;3例行剖腹探查术及术中活组织检查。(2)肿瘤分型和分期以及分化程度,①肿瘤分型和分期:93例肝门部胆管癌患者中,Bismuth-Corlette分型为Ⅰ型26例,Ⅱ型22例,Ⅲa型9例,Ⅲb型 18例,Ⅳ型18例; TNM分期为Ⅰ期7例,Ⅱ期34例,Ⅲ期22例,Ⅳ期30例;Mayo Clinic分期为1期20例,2期19例,3期51例,4期3例。②肿瘤分化程度:病理学检查结果显示93例患者肝门部胆管癌肿瘤分化程度中,高、中、低、黏液腺癌及乳头状腺癌分别为16、35、37、4、1例。(3)随访情况:93例患者均获得随访,随访时间为6~36个月,中位随访时间为24个月。93例患者生存时间为(21.4±2.1)个月。患者术后1、2、3年总体生存率分别为62.2%、34.9%、17.1%。(4)预后影响因素分析:①单因素分析结果显示:术前总胆红素水平、术前CA19-9水平、术前CA24-2水平、手术方式、淋巴结转移、血管侵犯、TNM分期、Mayo Clinic分期、肿瘤分化程度与肝门部胆管癌患者的预后相关(χ2=6.321,7.357,6.590,22.088,11.173,22.914,23.326,25.966,39.512,P<0.05)。②多因素分析结果显示:术前总胆红素水平、术前CA19-9水平、手术方式、血管侵犯、肿瘤分化程度是影响肝门部胆管癌患者预后的独立因素(比值比=1.002,1.001,2.690,2.626,0.420,95%可信区间为1.000~1.004,1.000~1.002,1.474~4.910,1.333~5.134,0.206~0.854,P<0.05)。(5)亚组分析:93例患者中,51例行根治性切除术,患者术后生存时间为(28.0±2.3)个月,1、2、3年生存率分别为75.3%、57.5%、25.7%;23例行姑息性切除术为(14.0±2.4)个月和60.9%、13.0%、0;19例行胆道引流或开腹探查术为(8.0±2.9)个月和31.6%、7.9%、0。根治性切除术患者生存情况分别与姑息性切除术、胆道引流或开腹探查术比较,差异均有统计学意义(χ2=10.939,18.343,P<0.05);姑息性切除术患者生存情况与胆道引流或开腹探查术比较,差异无统计学意义(χ2=2.803,P>0.05)。35例血管被肿瘤侵犯的患者中,18例单纯侵犯门静脉总体生存时间为(7.0±2.0)个月,术后1、2、3年生存率分别为14.5%、7.3%、0;8例单纯侵犯肝动脉总体生存时间为(10.0±2.1)个月,术后1、2、3年生存率分别为37.5%、18.8%、18.8%;两者生存情况比较,差异无统计学意义(χ2=0.905,P>0.05)。结论术前总胆红素水平、术前CA19-9水平、手术方式、血管侵犯及肿瘤分化程度是肝门部胆管癌患者预后的独立影响因素。肝门部胆管癌患者行根治性切除术与其他外科治疗比较更能延长术后生存时间。

     

    Abstract:  ObjectiveTo analyze the prognostic factors in the surgical treatment of hilar cholangiocarcinoma. MethodsThe retrospective case-control study was conducted. The clinicopathological data of 93 patients [61 males and 32 females, age (64±8)years with the range of 43-84 years] with hilar cholangiocarcinoma who underwent surgical treatments in the General Hospital of the Northern Theater from January 2010 to December 2017 were collected. According to preoperative different staging and intraoperative exploration of hilar cholangiocarcinoma, corresponding operations were performed. Observation indicators: (1) surgical treatment situations; (2) tumor typing, staging and degree of differentiation: ① tumor typing and staging, ② degree of tumor differentiation; (3) follow-up situations; (4) analysis of prognostic factors: ①univariate analysis, ②multivariate analysis; (5) subgroup analysis. Follow-up using outpatient examination and telephone interview was performed to detect survival time and survival rate of patients up to December 31, 2017. Kaplan-Meier method was used to calculate survival time and survival rate and to draw survival curves. Survival situations were analyzed by Log-rank test. The univariate analysis and multivariate analysis were performed using the Log-rank test and COX proportional hazard model respectively. Results(1) Surgical treatment situations: 93 patients underwent surgical treatments, including 51 undergoing radical resection, 23 undergoing palliative resection, 16 undergoing internal biliary drainage or external drainage, 3 undergoing abdominal laparotomy and intraoperative biopsy. (2) Tumor typing, staging and degree of differentiation. ① Tumor typing and staging: of the 93 patients with hilar cholangiocarcinoma, Bismuth-Corlette type Ⅰ, Ⅱ, Ⅲa, Ⅲb and Ⅳ were detected in 26, 22 , 9, 18 and 18 patients. TNM stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were detected in 7, 34, 22 and 30 patients, Mayo Clinic stage 1, 2, 3, 4 were detected in 20, 19, 51 and 3 patients. ② Degree of tumor differentiation: results of pathological examination showed 16 of 93 patients with highly differentiated adenocarcinoma, 35 with moderately differentiated adenocarcinoma, 37 with poorly differentiated adenocarcinoma, 4 with mucinous adenocarcinoma and 1 with papillary adenocarcinoma. (3) Follow-up situations: 93 patients were followed up for 6-36 months, with a median time of 24 months. The survival time of 93 patients was (21.4±2.1)months and the 1-, 2-, 3-year overall survival rates were 62.2%, 34.9% and 17.1%, respectively. (4) Analysis of prognostic factors: ① results of univariate analysis showed that preoperative level of TBil, preoperative level of CA19-9, preoperative level of CA24-2, surgical methods, lymph node metastasis, vascular invasion, TNM staging, Mayo Clinic staging, degree of tumor differentiation were related factors affecting prognosis of patients with hilar cholangiocarcinoma (χ2=6.321, 7.357, 6.590, 22.088, 11.173, 22.914, 23.326, 25.966, 39.512, P<0.05). ② Results of multivariate analysis showed that preoperative level of TBil, preoperative level of CA19-9, surgical methods, vascular invasion and degree of tumor differentiation were independent factors affecting prognosis of patients with hilar cholangiocarcinoma (odds ratio=1.002, 1.001, 2.690, 2.626, 0.420, 95% confidence interval: 1.000-1.004, 1.000-1.002, 1.474-4.910, 1.333-5.134, 0.206-0.854, P<0.05). (5) Subgroup analysis: of the 93 patients, the survival time of 51 undergoing radical resection was (28.0±2.3)months, and the 1-, 2-, 3-year survival rates were 75.3%, 57.5% and 25.7%, respectively; the survival time of 23 undergoing palliative resection was (14.0±2.4)months and the 1-, 2-, 3-year survival rates were 60.9%, 13.0%, 0, respectively; the survival time of 19 undergoing biliary drainage or open exploration was (8.0±2.9)months and the 1-, 2-, 3-year survival rates were 31.6%, 7.9%, 0, respectively. The survival of patients undergoing radical resection was significantly different from that of patients undergoing palliative resection, biliary drainage and open laparotomy respectively (χ2=10.939, 18.343, P<0.05). The survival of patients undergoing palliative resection was not statistically significant different from that of patients undergoing biliary drainage or exploration group (χ2=2.803, P>0.05). Of the 35 patients with vascular invasion, the overall survival time was (7.0±2.0)months and 1-, 2-, 3-year survival rates were 14.5%, 7.3%, 0 respectively in 18 with portal vein invasion only, (10.0±2.1)months and 37.5%, 18.8%, and 18.8% respectively in 8 with hepatic artery invasion, showing no statistically significant difference between the two groups (χ2=0.905, P>0.05). ConclusionsPreoperative level of TBil, preoperative level of CA19-9, surgical procedures, vascular invasion and degree of tumor differentiation are independent prognostic factors for patients with hilar cholangiocarcinoma. Radical resection can prolong the survival time of patients compared with other surgical treatments.

     

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