Intrahepatic cholangiocarcinomas were classified into two types based on their microscopic appearance. Tumors with histologic similarities to hilar cholangiocarcinomas (predominantly ductal adenocarcinomas with minor tubular components, if present, restricted to the invasive front) were defined as the perihilar type, whereas the others were classified as peripheral cholangiocarcinomas. Among the 47 cases examined in the present study, 26 (55%) were classified as the perihilar type, whereas 21 (45%) were the peripheral type. The perihilar type had higher pT stages and more frequently showed a periductal-infiltrating gross appearance and microscopic perineural infiltration than peripheral cholangiocarcinomas. The presence of low-grade biliary intraepithelial neoplasia in the adjacent bile ducts was only found in perihilar cholangiocarcinomas (6/21, 29%). The immunophenotype also differed between the two types with MUC5AC and MUC6 being more commonly expressed in the perihilar type. One-third of perihilar cholangiocarcinomas lacked the expression of SMAD4, suggesting SMAD4 mutations, whereas the loss of BAP1 expression and IDH1 mutations were almost restricted to the peripheral type (35 and 15%, respectively). Patients with perihilar cholangiocarcinoma had worse overall survival than those with peripheral cancer (P=0.027). A multivariate analysis identified the histologic classification as an independent prognostic factor (P=0.005, HR=3.638). Comparisons between intrahepatic and hilar cholangiocarcinomas also revealed that the molecular features and prognosis of perihilar cholangiocarcinomas were very similar to those of hilar cholangiocarcinomas. In conclusion, this histology-based classification scheme of intrahepatic cholangiocarcinomas will be useful and clinically relevant because it represents different underlying molecular features and has an independent prognostic value.

In the present multicentre study analysing a large cohort of healthy subjects and patients with LVDD, the normal range and the clinical relevance of the myocardial function of the LA using 2DSTE have been determined.

R ight ventricular (RV) function is closely coupled with subsequent morbidity and mortality in patients with diseases affecting the right heart chambers. [1][2][3][4][5][6][7] The most common cause of RV dysfunction is chronic left-sided heart failure. Complex factors such as pulmonary hypertension, intrinsic myocardial involvement, ventricular interdependence, and myocardial ischemia lead to RV dysfunction. 1 Therefore, assessment of RV function is clinically important in almost all patients with heart disease. However, the complex geometry of the RV poses a significant limitation to the reliable quantitation of RV volumes and ejection fraction (RVEF) using 2-dimensional transthoracic echocardiography. Although cardiac magnetic resonance (CMR) imaging is the gold standard for the evaluation of RV volumes and RVEF, 8,9 factors such as cost, portability, time consumption, and contraindications hinder its routine use in every patient. Three-dimensional transthoracic echocardiography (3DTTE) has the advantage of full-volume acquisition of the entire right ventricle, which may overcome the technical and clinical limitations of 2-dimensional transthoracic echocardiography. [10][11][12] Recent studies have validated the accuracy of 3DTTE-determined RV volumes and RVEF against CMR 13,14 and determined the reference values of RV volumes and RVEF in healthy subjects. 15,16 However, the prognostic value of RVEF is largely unknown. We hypothesized that RVEF assessed by 3DTTE (3DRVEF) would offer incremental value over left ventricular (LV) functional parameters for predicting future cardiac events. See Editorial by Fernández-Golfín and Zamorano See Clinical PerspectiveAccordingly, the aims of this study were (1) to validate the accuracy of 3DTTE-determined RV volumes and RVEF against CMR reference and (2) to evaluate the prognostic value of 3DRVEF to predict future cardiac death and major adverse cardiac events (MACEs) in a large number of patients.Background-Cardiac magnetic resonance is the gold standard for the evaluation of right ventricular (RV) volumes, but it is impractical to perform in every patient. Although reference values of RV volumes and RV ejection fraction by 3D transthoracic echocardiography (3DTTE) have been established, their prognostic values have not been elucidated yet. We hypothesized that RV ejection fraction measured by 3DTTE (3DRVEF) predicts future cardiovascular events. Methods and Results-In protocol 1, we determined the accuracy of RV volumes and RV ejection fraction measurements by 3DTTE against cardiac magnetic resonance in 60 subjects. In protocol 2, 3DRVEF was measured in 446 patients with various cardiovascular diseases. Study subjects were followed up to record cardiac death and major adverse cardiovascular events. In protocol 1, 3DTTE-determined RV end-diastolic volume, end-systolic volume, and RV ejection fraction had good correlations to those by cardiac magnetic resonance (r=0.74-0.90). In protocol 2, 38 cardiac deaths and 88 major adverse cardiovascular events occurred during a med...