Studies Of Circulating Tumor Cells In The Diagnoses Of Gallbladder Carcinoma And Cholangiocarcinoma

Background & Aims:Gallbladder carcinoma(GBC)and cholangioma(Cholangiocarcinoma)are both malignant tumors of the biliary system.Cholangiocarcinoma is divided into intrahepatic cholangiocarcinoma(ICC)and Extrahepatic Cholangiocarcinoma(EHC)according to the origin of the primary tumor in the biliary tree epithelium.Extrahepatic cholangiocarcinoma can be further subdivided into Hilar Cholangiocarcinoma(HCCA)and Distal Cholangiocarcinoma(DCCA).Biliary tumors generally have a high degree of malignancy with poor prognosis.So far,radical resection remains the only way to achieve a better prognosis.Generally,preoperative assessments which relies on tumor markers combined with imaging findings evaluate the feasibility of surgery and develop surgical plan.However,due to the special location of the biliary tract tumor,the complex surrounding structure,local spread,vascular invasion and lymph node metastasis are often not easily found in the preoperative assessment.Ultimately these factors have an adverse effect on the surgical procedure and outcome.Circulating Tumor Cells(CTCs)refer to the tumor cells which have shed from the primary tumor into the peripheral blood.They play an important role in tumor metastasis.Related studies have gradually confirmed that circulating tumor cells are closely related with tumor clinical stage and prognosis.Circulating Tumor Microemboli(CTM)refers to a cluster of cells that combined with two or more circulating tumor cells.It has more potential for invasion and metastasis than single circulating tumor cells.At present,the research of circulating tumor cells and microemboli are gradually expanded in different types of tumors.But,in the study of biliary tumors,its value in clinical application is not yet clear.The aim of this study was to evaluate the diagnostic efficacy of the tumor markers in patients with cholangiocarcinoma and gallbladder cancer by detecting the count of CTCs and the positive rate of CTM,and to explore its advantages compared with traditional tumor markers in disease diagnostic assessment.Methods:1?According to pre-designed criteria,76 patients were enrolled in the study.Venous blood was collected on the 1st day before operation.The circulating tumor cells and circulating tumor microemboli were identified within 2 hours by using the membrane filtration system.2?Clinical basic information and pathological data of those patients were collected after operation.Each patient was staged according to the AJCC 8th edition of the biliary tract tumor TNM staging.3?Statistical analysis was performed to evaluate the diagnostic efficacy of CTCS count,CEA level and CA19-9 level in different TNM staging in different biliary tumors.The difference of positive rates of CTM in different TNM staging also was analyzed.Results:1? In GBC group,at the cut-off of > 2,the sensitivity of the diagnosis of the distinction between GBC and benign disease was 95.45%,the specificity was 100%,and the area under the ROC curve was 0.964(P = 0.0001).CTCs showed a diagnostic sensitivity of 66.67%,specificity of 100%,the area under the ROC curve of 0.875(P = 0.0001)for T stage T1 + 2 and T3 + 4 when the cut-off value was >5.With a cut-off of >3,the CTCs discriminated TNM stage I + II and III +? with specificity and specificity of 85% and 100%,while the area under the ROC curve was 0.9(P = 0.0001).2?In ICC group,at the cut-off of > 2,the sensitivity of the diagnosis of the distinction between ICC and benign disease was 76.47%,and the specificity was 100%,and the area under the ROC curve was 0.916(P = 0.001).When the cut-off value was> 3,the diagnostic sensitivity and specificity of CTCs was 78.57% and 100% respectively,and the area under ROC curve was 0.905(P = 0.0001)for T stage T1 and T2+3+4.CTCs showed a diagnostic sensitivity of 100%,specificity of 71.43%,and an area under the ROC curve of 0.893(P = 0.0024)for M stage M0 and M1.With the cut-off of > 5,the CTCs discriminated TNM stage I + II and III +?with specificity and specificity of 58.33% and 100%,while the area under ROC curve was 0.808(P = 0.0045).3?In HCCA group,at the cut-off of > 2,the sensitivity of the diagnosis of the distinction between ICC and benign disease was 80%,and the specificity was 100%,and area under the ROC curve was 0.896(P = 0.001).However,the diagnostic efficacy of CTCs in TNM staging of HCCA was poor(P> 0.05).4?In DCCA group,at the cut-off of > 2,the sensitivity of the diagnosis of the distinction between ICC and benign disease was 91.67%,and the specificity was 100%,and the area under the ROC curve was 0.9333(P = 0.0001).With the cut-off of > 4,the CTCs discriminated T2 and T3 with specificity and specificity of 80% and 100%,while the area under ROC curve was 0.875(P = 0.0001).5?The positive rates of CTM in GBC,ICC,HCCA and DCCA were 0%,16%,12% and 16% respectively.The positive rates of CTM in each group were not significantly different in T stage,N stage,M stage and TNM stage(P> 0.05).Conclusion:1?CTCs count have a good diagnostic value in the distinction between benign and malignant diseases of biliary tumors.It can be used as a supplementary reference for traditional tumor markers.2?The positive rate of CTM is very low in biliary tract tumors,and there is no significant correlation between CTM and TNM stage.