There is a recently proposed subtype of hepatocellular carcinoma (HCC) that is histologically similar to usual HCC, but characterized by the expression of ''stemness''-related markers. A large-scale study on two different cohorts of HCCs was performed to investigate the clinicopathologic features and epithelial-mesenchymal transition (EMT)-related protein expression status of this subtype of HCCs. The expression status of stemnessrelated (e.g., keratin 19 [K19], cluster of differentiation [CD]133, epithelial cell adhesion molecule [EpCAM], and c-kit) and EMT-related markers (e.g., snail, S100A4, urokinase plasminogen activator receptor [uPAR], ezrin, vimentin, E-cadherin, and matrix metalloproteinase [MMP]2) were examined using tissue microarrays from cohort 1 HCCs (n 5 137). K19 protein expression in cohort 2 HCCs (n 5 237) was correlated with the clinicopathologic parameters and messenger RNA (mRNA) levels of K19, uPAR, VIL2, Snail, Slug, and Twist. K19, EpCAM, c-kit, and CD133 positivity were observed in 18.2%, 35.0%, 34.3%, and 24.8%, respectively. K19 was most frequently expressed in combination with at least one other stemness-related marker (92.0%). K19-positive HCCs demonstrated more frequent major vessel invasion and increased tumor size, compared to K19-negative HCCs (P < 0.05). K19 was most significantly associated with EMT-related protein expression (e.g., vimentin, S100A4, uPAR, and ezrin) (P < 0.05) and a poor prognosis (overall survival: P 5 0.018; disease-free survival: P 5 0.007) in cohort 1. In cohort 2, HCCs with high K19 mRNA levels demonstrated higher mRNA levels of Snail, uPAR, and MMP2 (P < 0.05). K19-positive HCCs demonstrated more frequent microvascular invasion, fibrous stroma, and less tumor-capsule formation, compared to K19-negative HCCs (P < 0.05). K19 expression was a significant independent predictive factor of poor disease-free survival (P 5 0.032). Conclusion: K19 was well correlated with clinicopathologic features of tumor aggressiveness, compared to other stemnessrelated proteins. K19-positive HCCs showed significantly increased EMT-related protein and mRNA expression, suggesting that they may acquire more invasive characteristics, compared to K19-negative HCCs through the up-regulation of EMT-associated genes.

The regional+alpha lymph node dissection enhanced the survival in the ICC patients with lymph node metastasis, and the exact nodal status could be confirmed by lymph node dissection in the pericholedochal lymph nodes.

Purpose: To determine whether peritumoral hypointensity seen on hepatobiliary phase images of preoperative gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) is useful for predicting microvascular invasion of hepatocellular carcinoma (HCC). Materials and Methods:This study was approved by the Institutional Review Board. In all, 104 HCC masses in 104 patients who had undergone EOB-MRI and liver surgery within 1 month after EOB-MRI were evaluated. Two radiologists independently recorded the presence of a peritumoral hypointensity on hepatobiliary phase. Interobserver agreement was assessed and consensus records were used. Tumor size was measured. A chi-square test and independent t-test were used for univariate analysis. Multiple logistic regression was performed to determine factors for predicting microvascular invasion. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of peritumoral hypointensity were calculated.Results: Sixty HCCs had microvascular invasion and 44 did not. Interobserver agreement in determining peritumoral hypointensity was excellent (k ¼ 0.83). By univariate analysis, peritumoral hypointensity and tumor size were significant for predicting microvascular invasion of HCC. On multiple logistic regression analysis, only peritumoral hypointensity was significant in predicting microvascular invasion of HCC (P ¼ 0.013). The sensitivity, specificity, PPV, and NPV of peritumoral hypointensity were 38.3%, 93.2%, 88.5%, and 52.6%, respectively. Conclusion:Peritumoral hypointensity on the hepatobiliary phase of EOB-MRI is not sensitive but has high specificity for predicting microvascular invasion of HCC.

Microvessel invasion is a major prognostic factor in hepatocellular carcinoma (HCC) that influences the suitability of surgery, but rarely can be evaluated preoperatively. This study was performed to identify preoperative MRI findings that reflect histopathological microvessel invasion in hepatocellular carcinoma. Gadobenate dimeglumine-enhanced four-arterial phase dynamic study and hepatobiliary phase images of preoperative MRI of 70 HCC lesions were retrospectively reviewed. Tumor size (cm), peritumoral enhancement, tumor margins, and radiological capsule were analyzed as radiological parameters reflecting microvessel invasion and were compared with histopathological references. The chi-square test and the independent t-test were used for univariate analysis, and a logistic regression analysis was performed for multivariate analysis. In univariate analysis, tumor size (p = 0.030), peritumoral enhancement (p < 0.001), and tumor margins (p = 0.007) were associated with microvessel tumor invasion. However, in multivariate analysis irregular circumferential peritumoral enhancement only showed statistical significance (odds ratio 13.0), suggesting a high probability of microvessel invasion of HCC. Irregular circumferential peritumoral enhancement on contrast-enhanced multi-arterial phase dynamic MRI could be a preoperative surrogate marker for microvessel tumor invasion.

Malignant SPTs are low-grade tumors with good prognosis. Adequate surgical intervention is necessary. Especially, SPTs over 5 cm in diameter need to be treated carefully because of the chance of malignant pathology. Careful long-term follow-up is necessary in those patients in case of possible tumor recurrences.