淋巴结转移对肝内胆管细胞癌患者预后的影响及临床相关因素研究

The impact of lymph node metastasis on the clinical parameters and prognosis of intrahepatic cholangiocarcinoma patients after curative resection

背景与目的:肝内胆管细胞癌(intrahepatic cholangiocarcinoma,ICC)是原发性肝癌中第二常见的病理学类型,起病隐匿,预后不佳。ICC常出现淋巴结转移(lymph node metastasis,LNM)。探讨肝十二指肠LNM与ICC患者临床相关因素及预后的关系。方法:共招募322例ICC患者在复旦大学附属中山医院行根治性肝肿瘤切除术,分析肝十二指肠LNM与临床病理学特征的关系及预后价值。结果:LNM与乙型肝炎病毒(hepatitis B virus,HBV)阳性、血清CA19-9>89 U/mL、肿瘤数目、肿瘤直径(>5 cm)、微血管侵犯、TNM分期、中性粒细胞/淋巴细胞比值(neutrophil-tolymphocyte ratio,NLR)显著相关。Kaplan-Meier分析显示,无LNM的ICC患者组的1、3和5年总生存率(overall survival,OS)分别为80.8%、53.4%和40.3%,显著高于伴有LNM组(47.4%、20.4%和10.2%,P<0.001)。无LNM的ICC患者组的1、3和5年无瘤生存率(recurrence-free survival,RFS)分别为62.6%、43.4%和36.3%,显著高于伴有LNM组(25.6%、16.6%和12.4%,P<0.001)。进一步研究发现,血清CA19-9>89 U/mL(P<0.001)、肿瘤直径>5 cm(P=0.042)、肿瘤数目(P<0.001)、微血管侵犯(P=0.022)、TNM分期(P<0.001)、NLR≥2.49(P=0.016)、淋巴细胞/单核细胞比值(lymphocyte-to-monocyte ratio,LMR)<4.45(P=0.048)及LNM(P<0.001)与ICC患者术后无瘤生存时间(time to recurrence,TTR)显著相关;血清CA19-9>89 U/mL(P<0.001)、肿瘤直径>5 cm(P=0.008)、肿瘤数目(P=0.002)、TNM分期(P<0.001)、NLR≥2.49(P<0.001)、LMR<4.45(P=0.002)及LNM(P<0.001)与ICC患者术后OS显著相关。多因素分析显示,血清CA19-9>89 U/mL、肿瘤数目、LNM是影响ICC患者术后TTR的独立预后因素;血清CA19-9>89 U/mL、肿瘤数目、LMR<4.45、LNM是影响ICC患者术后OS的独立预后因素。结论:肝十二指肠LNM是ICC患者术后的独立预后因素,准确判断LNM状态具有重要的临床意义。

Background and purpose:Intrahepatic cholangiocarcinoma(ICC)is the second most common pathological type of primary liver cancer.It has insidious onset and poor prognosis.Lymph node metastasis(LNM)is common in ICC.This study aimed to identify the relationship between LNM and clinical parameters and prognosis in patients with ICC after curative resection.Methods:A total of 322 patients with ICC who underwent a curative hepatic resection in Zhongshan Hospital,Fudan University were enrolled in this study.Clinicopathological parameters including LNM and serum CA19-9 were analyzed for long-term survival outcomes.Results:LNM was significantly correlated with hepatitis B virus(HBV)infection,preoperative serum CA19-9,tumor number,diameter of largest tumor nodule,microvascular invasion,TNM staging and neutrophil-to-lymphocyte ratio(NLR).Kaplan-Meier curve was applied to evaluate the clinicopathological parameters and prognosis.The 1-,3-,and 5-year overall survival(OS)rates were 80.8%,53.4%and 40.3%,respectively in LNM(-)group,significantly better compared with LNM(+)group(P<0.001)(47.4%,20.4%and 10.2%,respectively).The 1-,3-,and 5-year recurrence-free survival(RFS)rates were 62.6%,43.4%and 36.3%,respectively in LNM(-)group,significantly better compared with LNM(+)group(P<0.001)(25.6%,16.6%and 12.4%,respectively).We found preoperative serum CA19-9>89 U/mL(P<0.001),diameter of largest tumor nodule greater than 5cm(P=0.042),multiple tumor(P<0.001),micro vascular invasion(P=0.022),advanced TNM stage(P<0.001),NLR≥2.49(P=0.016),lymphocyte-to-monocyte ratio(LMR)<4.45(P=0.048)and LNM(P<0.001)had adverse impact on time to recurrence(TTR).As well,preoperative serum CA19-9>89 U/mL(P<0.001),diameter of largest tumor nodule greater than 5 cm(P=0.008),multiple tumor(P=0.002),advanced TNM stage(P<0.001),NLR≥2.49(P<0.001),LMR<4.45(P=0.002)and LNM(P<0.001)were negatively correlated with OS.Cox regression model indicated preoperative serum CA19-9>89 U/mL,multiple tumor,LNM were independent prognostic factors for TTR.Preoperative serum CA19-9>89 U/mL,multiple tumor,LMR<4.45,LNM were independent prognostic factors for OS of ICC patients.Conclusion:Hepatoduodenal ligament LNM is an independent prognostic factor of ICC patients after curative resection.It has important prognostic value to increase the detection rate of LNM.