腹腔淋巴结清扫对肝内胆管细胞癌预后影响的系统评价

Effect of abdominal lymphadenectomy on prognosis of intrahepatic cholangiocarcinoma: a systematic review and Meta analysis

  • 摘要: 目的:系统评价腹腔淋巴结清扫对肝内胆管细胞癌(ICC)预后因素的临床意义。
    方法:以intrahepatic cholangiocarcinoma AND survival AND surgery AND lymph OR vascular invasion为检索词,检索PubMed数据库。检索时间为2005年1月至2015年12月。从已查阅文章所附参考文献中手检可能漏查的文献;如报告不详或资料缺乏,通过信件与作者进行联系获取,以尽量增加纳入文献资料的完整性。由 2名研究者独立行文献筛选和提取数据,并进行文献质量评价。分析影响ICC术后预后的侵袭转移相关因素(血管侵犯、胆管侵犯、淋巴管侵犯、淋巴结转移、周围神经侵犯)和手术方式的相关因素(R0切除、淋巴结清扫);提取患者3、5年生存率和无瘤生存率;腹腔淋巴结清扫对患者预后的影响。各纳入研究结果间的异质性采用 χ2和I2检验。风险比(HR)和95%可信区间(95%CI)转换为Log(HR)和SE Log(HR)进行分析。将提供HR和95%CI的COX回归分析临床研究纳入Meta分析。发表偏倚采用漏斗图法Egger检验。
    结果:最终纳入符合系统评价标准的相关研究48篇,合计7 868例ICC患者,其中12篇研究纳入 Meta分析。7 868例ICC手术患者中,存在血管侵犯、胆管侵犯、淋巴管侵犯、淋巴结转移、周围神经侵犯者分别为30%(5%~98%)、40%(11%~59%)、45%(35%~65%)、28%(9%~100%)和25%(7%~55%);79%(35%~100%)的患者行R0切除,64%(9%~100%)的患者行淋巴结清扫。患者术后3、5年生存率分别为39%(16%~65%)和29%(5%~60%);术后3、5年无瘤生存率分别为34%(3%~60%)和23%(0~52%)。 Meta分析结果显示:淋巴结转移、血管侵犯是影响ICC患者的预后因素(HR=2.30,1.92,95%CI:1.94~2.73, 1.64~2.25,P<0.05)。无淋巴结转移的ICC患者,行淋巴结清扫后5年生存率为17%~64%,未行淋巴结清扫5年生存率为15%~64%,两者生存情况比较,差异无统计学意义(P>0.05)。淋巴结转移的ICC患者,行淋巴结清扫患者5年生存率为48%,未行淋巴结清扫患者5年生存率为11%,两者生存情况比较,差异有统计学意义(P<0.05)。
    结论:淋巴结转移和血管侵犯是影响ICC预后的危险因素;盲目行腹腔淋巴结清扫并不能改善患者预后;针对可疑淋巴结转移的患者,可积极行常规淋巴结清扫。

     

    Abstract: Objective:To systematically review the prognostic factors of intrahepatic cholangiocarcinoma (ICC) and clinical significance of abdominal lymphadenectomy.
    Methods:PubMed was queried with the terms of “intrahepatic cholangiocarcinoma, survival, surgery, lymph or vascular invasion” to find all studies published from January 2005 to December 2015. Authors were contacted by letters for the publications that were initially ineligible due to insufficient information for data extraction, responses were received, so these publications were included. Data were analyzed and evaluated by 2 independent researchers. Prognostic factors of ICC (vascular invasion, bile duct invasion, lymphatic vessel invasion, lymph node metastasis and peripheral nerve invasion) and relatedfactors of surgical method (R0 resection and lymph node dissected) were analyzed. The 3, 5year survival rate, tumorfree survival rate and effect of lymph node dissected for prognosis of patients were extracted. Heterogeneity was analyzed by the chisquared test and I2 test. The hazard ratio (HR) and 95% confidence interval (CI) were transformed to Log (HR) and standard errors (SE) Log (HR). HR and 95% CI of clinical factors associated with outcomes were done using univariate COX regression models. Publication bias was evaluated by the Egger′s method, visualizing with funnel plot.
    Results:A total of 48 publications including 7 868 patients with ICC were eligible to be included in this analysis, 12 of 48 publications were included in the Mata analysis. Of 7 868 patients with ICC, vascular invasion, bile duct invasion, lymphatic vessel invasion, lymph node metastasis, peripheral nerve invasion, R0 resection and lymph node dissected were detected in 30%(5%-98%), 40%(11%-59%), 45%(35%-65%), 28%(9%-100%), 25%(7%-55%), 79%(35%-100%) and 64%(9%-100%), respectively. The 3, 5year survival rate and 3, 5year tumorfree survival rate were 39%(16%-65%), 29%(5%-60%) and 34%(3%-60%), 23%(0-52%), respectively. The results of metaanalysis showed that lymph node metastasis and vascular invasion were factors affecting the prognosis of patients with ICC (HR=2.30, 1.92,95%CI: 1.94-2.73, 1.64-2.25, P<0.05). Among the patients without lymph node metastasis, 5year survival rate in patients with and without lymphadenectomy was 17%-64% and 15%-64%, respectively, showing no statistically significant difference (P>0.05). Among the patients with lymph node metastasis, 5year survival rate in patients with and without lymphadenectomy was 48% and 11%, respectively, showing a statistically significant difference (P<0.05).
    Conclusions:Lymph node metastasis and vascular invasion are the risk factors affecting the prognosis of patients with ICC. Routine lymphadenectomy for ICC cannot show survival benefit, while routine lymphadenectomy should be applied to patients with ICC and uncertain lymph node metastasis.

     

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