进展期胃癌病人发生腹腔脱落细胞学阳性的危险因素分析及风险预测评分模型建立

目的探讨影响进展期胃癌病人腹腔脱落细胞学阳性的危险因素,建立腹腔脱落细胞学阳性的风险预测评分模型。方法收集分析河北医科大学第四医院2012年2月至2018年12月期间开展的一项前瞻性、多中心、开放、随机对照Ⅲ期临床试验(NCT01516944)中的225例进展期胃癌病人临床病理资料,所有病人术中均行腹腔镜探查及腹腔脱落细胞学检查(500 mL生理盐水冲洗),检测腹腔脱落癌细胞的阳性率,分析影响进展期胃癌病人腹腔脱落细胞学阳性的临床病理因素。结果225例胃癌病人腹腔冲洗液中脱落细胞学阳性者32例,阳性率为14.22%。单因素分析结果显示,病人的年龄、肿瘤直径,浸润深度(cT分期)、组织学类型、肿瘤部位、淋巴结转移情况(cN分期)以及血清中肿瘤标志物癌胚抗原(CEA)、癌抗原72-4(CA72-4)、癌抗原19-9(CA19-9)的表达情况均是发生腹腔脱落细胞学阳性的危险因素(P<0.05);多因素分析显示,影响进展期胃癌病人发生腹腔脱落细胞学阳性的独立危险因素为:肿瘤浸润深度为cT4a~cT4b期OR=20.954,95%置信区间(CI):(1.610,12.651),P=0.020];CEA表达阳性OR=7.695,95%CI(1.307,8.669),P=0.001];CA72-4表达阳性OR=7.551,95%CI(2.255,25.283),P=0.001];CA19-9表达阳性OR=3.317,95%CI(1.011,10.883),P=0.048]。根据多因素Logistic回归结果建立风险预测方程:logit(p)=-7.088+3.042×X1(肿瘤浸润深度)+2.041×X2(CEA)+1.199×X3(CA19-9)+2.022×X4(CA72-4),采用Hosmer-Lemeshow检验检测回归方程的拟合优度(P=0.614)。采用受试者工作特征(ROC)曲线评价回归方程的区分度,曲线下面积为0.84495%CI(0.751,0.936),P=0.000]。病人术前肿瘤浸润深度为cT4a~cT4b期、血清中肿瘤标志物CEA、CA72-4、CA19-9表达阳性其发生腹腔脱落细胞学阳性风险评分分别为3、2、2、1分,病人发生腹腔脱落细胞学阳性的概率:评分≥4分者为19.44%,评分<4分者为4.94%。结论进展期胃癌病人CEA、CA72-4、CA19-9水平升高以及浸润程度为cT4a~cT4b期则提示可能存在腹腔脱落细胞学阳性。同时联合上述指标建立风险评分模型,能够有效预测进展期胃癌病例中发生腹腔脱落细胞学阳性的高风险病人。

Clinicopathological factors affecting cytologically positive peritoneal exfoliation in advanced gastric cancer

Objective To explore the risk factors for positive peritoneal abscission cytology in patients with advanced gastric cancer and establish a risk prediction scoring model for positive peritoneal abscission cytology.Methods From February 2012 to December 2018,clinicopathological data were reviewed for 225 patients with advanced gastric cancer in a prospective,multi-center,open,randomized controlled phaseⅢclinical trial(NCT01516944).Microscopic intraoperative exploration of abdominal cavity and peritoneal exfoliation cytology(500 mL normal saline flushing)were performed to detect the positive rate of peritoneal exfoliated cancer cells.And clinicopathological factors affecting the positive peritoneal exfoliation cytology were examined.Results Positive exfoliation cytology had a positive rate of 14.22%in peritoneal washing fluid.Univariate analysis revealed that patient age,tumor diameter,depth of invasion(cT stage),histological type,tumor location,lymph node metastasis(cN stage),serum tumor marker carcinoembryonic antigen(CEA),cancer antigen 72-4(CA72-4)and cancer antigen 19-9(CA19-9)were all risk factors for positive abdominal exfoliation cytology(P<0.05);multivariate analysis indicated that depth of tumor invasion was cT4a-cT4b stageOR=20.954,95%confidence interval(CI)(1.610,12.651),P=0.020],CEAOR=7.695,95%CI(1.307,8.669),P=0.001],CA72-4OR=7.551,95%CI(2.255,25.283),P=0.001]and CA19-9OR=3.317,95%CI(1.011,10.883),P=0.048]affected independent risk factors for positive abdominal exfoliation cytology.The risk prediction equation was established on the basis of the results of multivariate Logistic regression:logit(p)=-7.088+3.042×X1+2.041×X2+1.199×X3+2.022×X4 and Hosmer-Lemeshow test was utilized for detecting the goodness-of-fit of regression equation(P=0.614).ROC curve was employed for evaluating the discrimination of regression equation.The area under the curve was 0.84495%CI(0.751,0.936),P=0.000].The preoperative tumor infiltration depth was cT4a-cT4b,CEA,CA72-4 and CA19-9 were positive and the positive risk scores of abdominal exfoliation were 3,2,2 and 1.The probability of positive abdominal exfoliation cytology was 19.44%in patients with 4 points and 4.94%in those with scores<4 points.Conclusion The elevated levels of CEA,CA72-4 and CA19-9 in patients with advanced gastric cancer and the degree of infiltration in cT4a-cT4b stage suggest that there may be a positive cytology for abdominal abscission.At the same time,the above-mentioned indicators are utilized for establishing a risk scoring model for effectively predicting high-risk patients with positive peritoneal cytology in the development of gastric cancer.