| Background and objectIntrahepatic cholangiocarcinoma(ICC)is the second most common primary liver cancer after hepatocellular carcinoma(HCC),accounting for 5-15%of all primary liver cancer.Surgical resection is still believed to be the most effective management for ICC patients.Due to the lack of typical clinical manifestations,most patients were diagnosed in the terminal stage.Surgical resection is still believed to be the most effective treatment method for ICC patients.Given the suboptimal management of ICC and the limited progress in adjuvant treatment,an additional reliable prognostic predicator is urgently needed to provide a guide towards a more active and effective treatment.As a morphological phenomenon,tumor budding was proved to be a mostly accepted favorable prognostic factor in many digestive system malignant tumors.However,the relationship between tumor budding and prognosis of ICC has not been reported.In this study,ICC patients with complete clinicopathological data and follow-up information were analyzed retrospectively to explore the relationship between tumor budding and prognosis of ICC patients,which is expected to provide a new idea for the treatment of ICC.MethodsThe clinicopathological data,postoperative treatment and follow-up information of patients undergoing radical resection for intrahepatic cholangiocarcinoma between January 2011 and October 2016 were retrospectively analyzed.All the diagnoses were ultimately confirmed both clinically and pathologically.All histomorphological and clinical data were retrospectively analyzed from the corresponding hematoxylin-eosin(HE)stained slides and medical reports,respectively.Histological analysis of all resected specimens was performed to assess tumor diameter,number,morphology,differentiation,margin,vascular and biliary invasion,lymph node status,and adjacent organ invasion.Tumor budding was defined as a single or a cluster of<5 tumor cells at the invasion front.The number of tumor budding was counted in a×200 microscopic field(0.785mm2).Based on receiver operation curve(ROC),the number of tumor budding<15 was low-grade group,and≥15was defined as high-grade group.Multivariate analysis were performed on predictors of the tumor.Statistical analyses were conducted using SPSS 22.0 statistical software.Quantitative results were expressed as the mean±standard deviation.The counting data is expressed by the percentage of the number.The Mann-Whitney U-test was used to describe the normality of each continuous parameter’s distribution.χ2-test was used for the analysis of the categorical variables in the low-grade and high-grade groups.The associations between clinical and histopathological parameters with DFS and OS were analyzed by the Kaplan-Meier curves and compared by the log-rank test.Multivariate analysis was done by Cox proportional hazard model.P<0.05 was considered statistically significant.Results1.Among the 82 patients,low-grade group was observed in 32 cases and high-grade group in 50.2.High-grade group appeared to develop tumors with higher CA19-9,poor differentiation,larger tumor diameter,advanced stage and high risks of lymph nodem etastasis(respectively χ2=5.470,4.359,5.101,4.696,5.960,all P<0.05).3.With respect to the other quantitative clinical parameters including age,gender,CEA,AFP,TBil,albumin,AST,ALT,no significant differences were observed in the two groups(all P>0.05).4.Univariate analysis showed that tumor budding,CA19-9,differentiation,tumor diameter,T classification and lymphnode metastasis were related to the overall survival of patients with ICC(respectively χ2=11.704,4.876,5.056,5.152,8.442,16.725,all P<0.05).5.Kaplan-Meier curve showed that the high grade group had a major adverse effect on the OS(P=0.001)of the patients.6.On multivariable analysis,high-grade group was a significant independent predictor of worse OS(HR=2.707 95%CI 1.558-4.705,P<0.001).ConclusionsHigh-grade tumor budding was an independent prognostic factor of ICC. |
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