The Impact Of Microvascular Invasion In The Prognosis Of Intrahepatic Cholangiocarcinoma After Curative Resection

Background and aim: Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor originated from intrahepatic bile duct epithelium,one of liver malignant tumors.Surgical resection is still the most effective treatment method for it,however the postoperative prognosis is poor.So it is of great value to explore the prognostic factors for these patients.Among them,the prognostic value of microvascular invasion(MVI)for ICC patients is still unclear,and there are still few studies on the prediction of MVI in preoperative ICC patients.The purpose of this study was to explore the effect of MVI on the prognosis of ICC patients after curative resection.Furthermore,we explored the related preoperative risk factors of MVI in ICC patients,and built a prediction model based on preoperative indicators.Methods: The clinicopathological data of 704 ICC patients who underwent curative resection from December 2009 to December 2017 were retrospectively collected from13 hospitals.Cox proportional risk regression model was used to analyze the independent risk factors of the prognosis of ICC patients after radical surgical resection before and after Propensity Score Matching(PSM).Meanwhile,Kaplan-Meier method was used to analyze the Overall Survival(OS)and Recurrence Free Survival(RFS)of the MVI-positive group and MVI-negative group before and after matching,and log-rank test was used to compare the differences between the two groups.Subsequently,341 patients from the single center of Easten Hepatobiliary Hospital in the above multi-center retrospective cohort were randomly divided into the training group and the validation group at a 7:3 ratio.Logistic regression was used to analyze the MVI related influencing factors in the training group,and a nomogram prediction model was constructed based on the multivariate results.The accuracy of the prediction model was evaluated by the Index of Concordance(C-Index),and the consistency of the prediction model with the actual situation in the training group and the validation group was evaluated by the calibration curve.Results:(1)A total of 704 patients after ICC were included,and the positive rate of MVI was 11.5%.Multivariate Cox regression analysis showed that: before PSM matching,preoperative Child-Pugh grade(HR=1.394,95%CI 1.098-1.769,p=0.006),total bilirubin(HR=1.320,95%CI 1.052-1.648,p=0.014),carcinoembryonic antigen(HR=1.364,95%CI 1.060-1.754,p=0.016),pathological tumor diameter(HR=1.560,95%CI 1.236-1.968,p<0.001),pathological satellite(HR=1.487,95%CI 1.175-1.882,p=0.001),pathological surgical margin distance(HR=0.777,95%CI 0.608-0.992,p=0.043)and MVI(HR=1.399,95%CI 1.022-1.916,p=0.036)were independent risk factors for OS.Preoperative Child-Pugh grade(HR=1.539,95%CI 1.221-1.939,p<0.001),total bilirubin(HR=1.332,95%CI 1.074-1.651,p=0.009),range of liver resection(HR=1.535,95%CI 1.231-1.915,p<0.001),satellite(HR=1.511,95%CI1.206-1.893,p<0.001),MVI(HR=1.742,95%CI 1.303-2.329,p<0.001)was an independent risk factor for RFS.After PSM matching,Child-Pugh grade(HR=2.098,95%CI 1.344-3.274,p=0.001)and MVI(HR=1.576,95%CI 1.096-2.266,p=0.014)were independent risk factors for OS of ICC patients after curative resection.Hepatectomy range(HR=2.147,95%CI 1.386-3.326,p=0.001)and MVI(HR=2.057,95%CI 1.445-2.929,p<0.001)were independent risk factors for RFS.(2)The survival curves of OS(p=0.001)and RFS(p<0.001)before PSM matching and OS(p=0.002)and RFS(p<0.001)after matching were significantly different between the MVI positive group and MVI negative group.(3)A total of 341 patients after ICC operation in Eastern Hepatobiliary Hospital were included for analysis of related factors of MVI in ICC patients.Logistic regression multivariate results showed that:age(OR=0.962,95%CI 0.926-1.000,p=0.049),gamma-glutamyl transpeptidase(OR=1.005,95%CI 1.002-1.007,p=0.001)and preoperative tumor number(OR=3.491,95%CI 1.496-8.148,p=0.004)were independent risk factors for MVI.Furthermore,the prediction model in the form of nomogram was constructed.The model showed good prediction ability in both the training group(C-index=0.7622)and the validation group(C-index=0.7591),and the calibration curve showed good consistency between the model and the reality.Conclusion: MVI is an independent risk factor for poor prognosis after curative resection in ICC patients.Age,γ-glutamyltransferase and preoperative tumor number were independent risk factors for MVI in ICC patients.The prediction model constructed further showed good predictive ability in both the training group and the validation group and was consistent with the reality.