胆囊癌临床和病理学因素与神经浸润的相关性研究

Analysis of perineural invasion with clinicopathological factors and prognosis for curatively resected gallbladder carcinoma

目的探讨胆囊癌临床和病理学因素与神经浸润的相关性及神经浸润对预后的影响。方法回顾性分析2013年1月至2020年12月于西安交通大学第一附属医院肝胆外科行根治性切除的548例胆囊癌患者的临床、病理学资料和随访资料。男性173例,女性375例,年龄[M(IQR)]62(14)岁(范围:30~88岁)。分析胆囊癌临床和病理学特征与神经浸润的相关性;将患者的临床和病理学资料纳入预后分析,使用Kaplan-Meier法绘制生存曲线。单因素生存分析采用Log-rank检验,多因素分析采用Cox比例风险回归。结果548例胆囊癌患者中,59例(10.8%)患者发生神经浸润。单因素分析结果显示,胆囊癌的血清胆红素水平、血清癌胚抗原水平、CA19-9水平、T分期、淋巴结转移、肝脏侵犯、脉管癌栓、肿瘤位置等因素与神经浸润相关(P值均<0.05);多因素分析结果显示,黄疸、血清CA19-9水平升高、血清癌胚抗原升高、T分期为T4期、脉管癌栓、肿瘤位于胆囊管和(或)颈部是胆囊癌神经浸润的独立相关因素。对367例T3~4期胆囊癌患者进行生存分析,伴神经浸润的胆囊癌患者预后差于无神经浸润患者(中位生存时间:12.0个月比34.7个月,P<0.01)。单因素分析结果提示,神经浸润、胆囊结石、胆囊息肉、CA125、癌胚抗原、CA19-9、血清胆红素水平、肿瘤位置、N分期、肝脏侵犯、肿瘤分化程度是胆囊癌患者根治性切除术后的预后因素(P值均<0.05);Cox多因素分析结果显示,神经浸润、N分期、肝脏侵犯、胆囊结石、肿瘤分化程度是胆囊癌患者根治性切除术后的独立预后因素(P值均<0.05)。结论黄疸、血清CA19-9水平升高、血清癌胚抗原水平升高、T分期为T4期、脉管癌栓、肿瘤位于胆囊管和(或)颈部是胆囊癌发生神经浸润的独立相关因素,胆囊癌神经浸润是T3~4期胆囊癌根治性切除术后的独立预后因素。

Objective To examine the correlation between perineural invasion and clinicopathological factors and the role of perineural invasion on the prognosis of patients with curatively resected gallbladder carcinoma.Methods The clinicopathological and follow-up data of 548 patients with gallbladder carcinoma who underwent radical surgery from the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2020 were analyzed retrospectively.There were 173 males and 375 females,with age(M(IQR))of 62(14)years(range:30 to 88 years).The correlations between perineural invasion and the clinicopathological features were analyzed.The relationship between prognosis and clinicopathological factors were further analyzed.The survival curve was drawn using the Kaplan-Meier method.The univariate analysis and multivariate analysis were done using the Log-rank test and Cox proportional hazard model respectively.Results Radical resection was performed in 548 cases,including 59 cases(10.8%)with perineural invasion.The results of univariate analysis showed that perineural invasion was related to serum bilirubin level,serum carcinoembryonic antigen(CEA)level,CA19-9 level,T stage,lymph node metastasis,liver invasion,vessel invasion and tumor location(all P<0.05).The results of multivariate analysis showed that jaundice,high-level serum CA19-9,high-level serum CEA,T4 stage,vessel invasion and tumor located in the neck or cystic duct of the gallbladder were independent risk factors of perineural invasion in gallbladder carcinoma.Survival of 367 patients in T3-T4 stages were analyzed.The prognosis of gallbladder carcinoma patients with perineural invasion was significantly worse than that of patients without perineural invasion(median survival time:12.0 months vs.34.7 months,P<0.01).Univariate analysis showed that perineural invasion,gallbladder stones,gallbladder polyps,CA125,CEA,CA19-9,serum bilirubin level,tumor location,N stage,liver invasion and pathological differentiation were independent risk factors affecting prognosis of patients with gallbladder carcinoma(all P<0.05).The results of Cox proportional hazard model showed that perineural invasion,N stage,liver invasion,gallbladder stones,pathological differentiation were independent risk factors affecting prognosis of patients with gallbladder carcinoma(all P<0.05).Conclusions Jaundice,high-level serum CA19-9,high-level serum CEA,T4 stage,vessel invasion and tumor located in the neck or cystic duct of the gallbladder are independent risk factors for perineural invasion of gallbladder carcinoma.Perineural invasion is one of the independent risk factors affecting the prognosis of T3-T4 stage gallbladder carcinoma.