This paper presents the first version of clinical practice guidelines for intrahepatic cholangiocarcinoma (ICC) established by the Liver Cancer Study Group of Japan. These guidelines consist of 1 treatment algorithm, 5 background statements, 16 clinical questions, and 1 clinical topic, including etiology, staging, pathology, diagnosis, and treatments. Globally, a high incidence of ICC has been reported in East and Southeast Asian countries, and the incidence has been gradually increasing in Japan and also in Western countries. Reported risk factors for ICC include cirrhosis, hepatitis B/C, alcohol consumption, diabetes, obesity, smoking, nonalcoholic steatohepatitis, and liver fluke infestation, as well as biliary diseases, such as primary sclerosing cholangitis, hepatolithiasis, congenital cholangiectasis, and Caroli disease. Chemical risk factors include thorium-232, 1,2-dichloropropane, and dichloromethane. CA19-9 and CEA are recommended as tumor markers for early detection and diagnostic of ICC. Abdominal ultrasonography, CT, and MRI are effective imaging modalities for diagnosing ICC. If bile duct invasion is suspected, imaging modalities for examining the bile ducts may be useful. In unresectable cases, tumor biopsy should be considered when deemed necessary for the differential diagnosis and drug therapy selection. The mainstay of treatment for patients with Child-Pugh class A or B liver function is surgical resection and drug therapy. If the patient has no regional lymph node metastasis (LNM) and has a single tumor, resection is the treatment of choice. If both regional LNM and multiple tumors are present, drug therapy is the first treatment of choice. If the patient has either regional LNM or multiple tumors, resection or drug therapy is selected, depending on the extent of metastasis or the number of tumors. If distant metastasis is present, drug therapy is the treatment of choice. Percutaneous ablation therapy may be considered for patients who are ineligible for surgical resection or drug therapy due to decreased hepatic functional reserve or comorbidities. For unresectable ICC without extrahepatic metastasis, stereotactic radiotherapy (tumor size ≤5 cm) or particle radiotherapy (no size restriction) may be considered. ICC is generally not indicated for liver transplantation, and palliative care is recommended for patients with Child-Pugh class C liver function.

Many studies support the hypothesis that specific microRNA (miRNA) expression in various human cancers including hepatocarcinogenesis is closely associated with diagnosis and prognosis. In hepatocellular carcinoma (HCC), malignancy level is related to the degree of histological differentiation. In order to establish a novel biomarker that can determine the degree of malignancy and forecast patient prognosis, we performed a microarray analysis to investigate the miRNA expression profiles in 110 HCC which were comprised of 60 moderately, 30 poorly, and 20 well differentiated HCC. We found that the expression of 12 miRNAs varied significantly according to the degree of histological differentiation. Particularly, miR-18b expression in poorly differentiated HCC was significantly higher than in well differentiated HCC. Based on miRanda and Targetscan target search algorithms and Argonaute 2 immunoprecipitation study, we noted that miR-18b can control the expression of trinucleotide repeat containing 6B (TNRC6B) as a target gene. Additionally, in two hepatoma cell lines, we found that over-expression of miR-18b or down-regulation of TNRC6B accelerated cell proliferation and loss of cell adhesion ability. Finally, we observed that after surgical resection, HCC patients with high miR-18b expression had a significantly shorter relapse-free period than those with low expression. miR-18b expression is an important marker of cell proliferation and cell adhesion, and is predictive of clinical outcome. From a clinical point of view, our study emphasizes miR-18b as a diagnostic and prognostic marker for HCC progression.

Background Recently, the Liver Cancer Study Group of Japan (LCSGJ) staging system for intrahepatic cholangiocarcinoma (ICC) was followed by a proposal of the American Committee on Cancer (AJCC)/International Union Against Cancer (UICC) system. The present study aimed to assess the accuracy of both systems to predict survival after curative resection for mass‐forming ICC and to establish a new staging system based on survival analysis results. The present study was conducted as a project study of the Japanese Society of Hepato‐Biliary‐Pancreatic Surgery. Methods Clinical data from 233 patients who underwent curative resection for mass‐forming ICC were retrospectively reviewed. Survival analysis was performed to identify predictors of postoperative outcomes, and a new staging system was established. The survival stratification of our proposed system was compared with two previous staging systems. Results A N0M0 cohort analysis demonstrated that tumor size, tumor number, and vascular invasion were independently associated with survival after curative resection for mass‐forming ICC, whereas serosal and periductal invasion were not. Of patients with nodal metastases, patients with T4 tumor had significantly lower overall survival rate than patients with T1, T2, or T3 tumor. Thus, we proposed a new staging system as follows: serosal invasion was excluded from the LCSGJ T categories, and patients with nodal metastases were divided into stage IVA or IVB according to T classification. The new system better stratified survival after curative resection for mass‐forming ICC than the two previous systems. Conclusions The AJCC/UICC staging system failed to stratify the Japanese patients with mass‐forming ICC. The new staging system provided better survival prediction in the patients who underwent curative resection for mass‐forming ICC, although further studies are necessary to evaluate the impact of tumor size on survival.