Hypointense nodules without arterial hyperenhancement at gadoxetic acid–enhanced MRI correspond to hepatocellular carcinoma or premalignant hepatocellular nodules. Background Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) at gadoxetic acid–enhanced MRI may indicate hepatocellular carcinoma (HCC) or nonmalignant ci...

The first edition of the 'Standardized Pathology Report for Colorectal Cancer,' which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of "standard data elements" and "conditional data elements." Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as "standard data elements," while other prognostic factors and factors related to adjuvant therapy are classified as "conditional data elements" so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.

Background: Although surgical resection is the only potentially curative treatment for biliary tract cancer, the prognosis remains poor after a major operation such as pancreatoduodenectomy or hepatectomy. We aimed to investigate the impact of preoperative body compositions on long‐term survival of patients undergoing resection of biliary tract cancer.Methods: We analysed data of patients diagnosed with biliary tract cancer who underwent surgery from 2009 to 2015. Skeletal muscle area, skeletal muscle radiation attenuation, and visceral and subcutaneous adipose tissue areas were measured from the computed tomography images at L3 vertebral levels obtained before resection of cancer. Patients were divided into two groups based on the sex‐specific median values for each parameter, and long‐term survival was compared between the groups.Results: A total of 371 patients (women, 39.6%; mean age, 66.2 ± 9.6 years) were finally included in the analysis. Patients with low skeletal muscle index (SMI) had significantly shorter median survival than those with high SMI (29 vs. 39 months; P = 0.026). Patients with low skeletal muscle attenuation (SMA) also showed reduced survival compared with those with high SMA (median survival 25 vs. 60 months; P = 0.002). Combining these two factors, survival was highest in the high SMI/high SMA group (reference) and lowest in the low SMI/low SMA group (hazard ratio, 2.18; 95% confidence interval, 1.44–3.30). Visceral and subcutaneous adipose tissue areas were not associated with long‐term survival.Conclusions: Low SMI and low SMA on computed tomography scan have a negative impact on survival after resection of biliary tract cancer. They can be used in preoperative risk assessment to assist in treatment decision making.

BRAF and KRAS mutations are well-established biomarkers in anti-EGFR therapy. However, the prognostic significance of these mutations is still being examined. We determined the prognostic value of BRAF and KRAS mutations in Korean colorectal cancer (CRC) patients. From July 2010 to September 2013, 1096 patients who underwent surgery for CRC at Seoul St. Mary’s Hospital were included in the analysis. Resected specimens were examined for BRAF, KRAS, and microsatellite instability (MSI) status. All data were reviewed retrospectively. Among 1096 patients, 401 (36.7%) had KRAS mutations and 44 (4.0%) had BRAF mutations. Of 83 patients, 77 (92.8%) had microsatellite stable (MSS) or MSI low (MSI-L) status while 6 (7.2%) patients had MSI high (MSI-H) status. Patients with BRAF mutation demonstrated a worse disease-free survival (DFS, HR 1.990, CI 1.080–3.660, P = 0.02) and overall survival (OS, HR 3.470, CI 1.900–6.330, P < 0.0001). Regarding KRAS status, no significant difference was noted in DFS (P = 0.0548) or OS (P = 0.107). Comparing the MSS/MSI-L and MSI-H groups there were no significant differences in either DFS (P = 0.294) or OS (P = 0.557). BRAF mutation, rather than KRAS, was a significant prognostic factor in Korean CRC patients at both early and advanced stages. The subgroup analysis for MSI did not show significant differences in clinical outcome. BRAF should be included in future larger prospective biomarker studies on CRC.

A predictive biomarker of immune checkpoint inhibitor (ICI)-based treatments in hepatocellular carcinoma (HCC) has not been clearly demonstrated. In this study, we focused on the infiltration and programmed death ligand 1 (PD-L1) expression of tumor-associated macrophages (TAMs) in the tumor microenvironment of HCC. Immunohistochemistry demonstrated that PD-L1 was preferentially expressed on CD68⁺ macrophages in the tumor microenvironment of HCC, suggestive of its expression in TAMs rather than in T cells or tumor cells (P < 0.05). A co-culture experiment using activated T cells and M2 macrophages confirmed a significant increase in T cell functionality after the pretreatment of M2 macrophages with anti-PD-L1. Syngeneic mouse model experiments demonstrated that TAMs expressed PD-L1 and tumors treated with anti-PD-L1 showed smaller diameters than those treated with IgG. In these mice, anti-PD-L1 treatment increased activation markers in intratumoral CD8⁺ T cells and reduced the size of the TAM population. Regarding nivolumab-treated patients, three of eight patients responded to the anti-PD-1 treatment. The percentage of Ki-67-positive CD4⁺ and CD8⁺ T cells was higher in responders than non-responders after nivolumab. Overall, PD-L1 expression on TAMs may be targeted by immune-based HCC treatment, and ICI treatment results in the reinvigoration of exhausted CD8⁺ T cells in HCC.

The aim of this study was to investigate the role of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)–enhanced magnetic resonance imaging (MRI) in predicting the histological grade of hepatocellular carcinoma (HCC) according to the hepatic function. Eighty-one consecutive patients with 122 histologically proven HCCs who underwent Gd-EOB-DTPA–enhanced MRI before resection (45 HCCs in 42 patients) or transplantation (77 HCCs in 39 patients) were analyzed retrospectively. We calculated the relative enhancement ratios (RER), which is the ratio of the relative intensity of a tumor versus the surrounding parenchyma on hepatobiliary phase images to the relative intensity on unenhanced MRI scans. We then analyzed the correlation between the RER and the tumor differentiation grade in patients with various degrees of hepatic function. The degree of tumor enhancement, which included the precontrast relative intensity ratio (RIR), the postcontrast RIR, and the RER, for well-differentiated (WD) HCCs was significantly higher than the degree of tumor enhancement for moderately differentiated and poorly differentiated (PD) HCCs (P = 0.001 and P = 0.001, respectively, for precontrast RIRs; P < 0.001 and P < 0.001, respectively, for postcontrast RIRs; and P = 0.01 and P = 0.001, respectively, for RERs). In a subgroup analysis based on liver function, the correlation between the histological grade and the enhancement ratio was demonstrated only in the group of patients with Child-Pugh class A cirrhosis. The accuracy of postcontrast RIRs for predicting WD and PD HCCs was favorable; the areas under the receiver operating characteristic curves were 0.896 [95% confidence interval (CI) = 0.817–0.974] and 0.769 (95% CI = 0.658–0.879), respectively. In conclusion, the hepatobiliary phase of Gd-EOB-DTPA–enhanced MRI may help to predict the differentiation of HCCs, especially in HCC patients with Child-Pugh class A cirrhosis before liver transplantation or resection. Liver Transpl, 2012. © 2012 AASLD.