We conducted a multicenter retrospective analysis to evaluate the efficacy of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. We enrolled 36 patients with pathologically proven, unresectable combined hepatocellular and cholangiocarcinoma treated with systemic chemotherapy. The log‐rank test determined the significance of each prognostic factor. Elevated alpha‐fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19‐9 levels were observed in 58.3%, 16.7% and 38.9% of patients, respectively. First‐line chemotherapy included platinum‐containing regimens consisting of gemcitabine/cisplatin (n = 12) and fluorouracil/cisplatin (n = 11), sorafenib (n = 5) and others (n = 8). The median overall and progression‐free survival times were 8.9 and 2.8 months, respectively, with an overall response rate of 5.6%. Prognostic factors associated with negative outcomes included poor performance status, no prior primary tumor resection, a Child‐Pugh class of B, and elevated carcinoembryonic antigen levels with a hazard ratio of 2.25, 2.48, 3.25 and 2.84 by univariate analysis, respectively. The median overall survival times of the gemcitabine/cisplatin, fluorouracil/cisplatin, sorafenib and other groups were 11.9, 10.2, 3.5 and 8.1 months, respectively. Multivariate analysis revealed that the overall survival of patients within the sorafenib monotherapy group was poor compared with platinum‐containing regimens (HR: 15.83 [95% CI: 2.25‐111.43], P = .006). All 7 patients in the sorafenib group had progressive disease, including 2 patients with second‐line therapy. In conclusion, the platinum‐containing regimens such as gemcitabine/cisplatin were associated with more favorable outcomes than sorafenib monotherapy for unresectable combined hepatocellular and cholangiocarcinoma.

BackgroundEpithelioid hemangioendothelioma is an exceedingly rare sarcoma often occurring as an indolent angiocentric vascular tumor at various anatomic sites. Few reports have evaluated large case series of epithelioid hemangioendothelioma.MethodsWe conducted a retrospective analysis of the clinical data of 42 consecutive patients with epithelioid hemangioendothelioma who were pathologically diagnosed between 1990 and 2014 at 13 Japanese tertiary hospitals. We analyzed their clinical characteristics, tumor features and prognostic factors.ResultsThe study included 22 men and 20 women, with a median age of 54 (range, 18–78) years. Pain was the most common symptom, occurring in 15 (68%) of the 22 symptomatic patients. The median maximum tumor diameter was 4.0 (range, 1.0–12.8) cm. The most commonly involved organs were the liver (81%), lungs (57%), and bones (12%). The overall survival rates were 79.5% at 1 year and 72.0% at 5 years. Substantially better survival was observed in asymptomatic patients than in symptomatic patients (P = 0.03), and better survival was also ovserved in patients with Ki-67 index ≤10% than in those with Ki-67 index > 10% (P = 0.04). By multivariate analysis, tumor size > 3.0 cm was associated with decreased survival (P = 0.049, hazard ratio 13.33).ConclusionsThis study showed the clinical characteristics of Japanese patients with epithelioid hemangioendothelioma. Tumor size > 3.0 cm is an independent indicator of a poor prognosis in epithelioid hemangioendothelioma. The presence of symptoms at the time of diagnosis and high Ki-67 index implied poor survival.

Background and study aims: Preoperative diagnosis of the pathological grade of intraductal papillary mucinous neoplasms (IPMNs) is difficult. This study aimed to evaluate the accuracy of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with time???intensity curve analysis in differentiating between low or intermediate grade dysplasia (LGD/IGD) and high grade dysplasia or invasive carcinoma (HGD/invasive carcinoma) in IPMNs and to assess correlation between the time???intensity curve parameters and tumor microvessel density. Patients and methods: Data from 30 patients with resected IPMNs (14 LGD/IGD, 16 HGD/invasive carcinoma) who underwent CH-EUS with time???intensity curve analysis were evaluated retrospectively. Time???intensity curve parameters and the microvessel density of the mural nodule were compared between the HGD/invasive carcinoma and LGD/IGD groups; the diagnostic accuracy of the time???intensity curve parameters was evaluated. Results: The echo intensity change and echo intensity reduction rate of the mural nodule, and the nodule/pancreatic parenchyma contrast ratio were significantly higher in the HGD/invasive carcinoma group than in the LGD/IGD group (P?

BackgroundEndoscopic retrograde cholangiography using a short double-balloon endoscope (DB-ERC) is a promising minimally-invasive method for accessing hepaticojejunostomy (HJ) anastomosis in patients with surgically altered anatomy. We aimed to evaluate the immediate and long-term outcomes of balloon dilatation for benign HJ anastomotic stricture (HJAS) in patients who had previously undergone Whipple’s procedure using a DB-ERC.MethodsWe conducted a retrospective analysis of 46 patients who underwent balloon dilatation alone with a DB-ERC for benign HJAS between November 2008 and November 2014. The median follow-up duration was 3.5 (interquartile range [IQR], 1.9–5.1) years.ResultsThe technical and clinical success rates were 100%, and adverse events occurred in 7% (3/46, cholangitis). The median hospitalization period was seven (IQR, 5–10) days. Of 42 patients (91%) followed-up for > 1 year, 24 (51%) had recurrent HJAS at a median of 1.2 (IQR, 0.6–2.9) years after balloon dilatation. The cumulative anastomotic patency rates at 1, 2, and 3 years were 73, 55, and 49%, respectively. In univariate analysis, early stricture formation (< 1 year) was a risk factor for recurrent stenosis, although no statistically significant risk factors were observed in multivariate analysis.ConclusionsEndoscopic balloon dilatation with DB-ERC for benign HJAS is effective and safe, having good immediate technical success and few adverse events. Further improvements to this procedure are needed to prevent recurrent HJAS.

Serum and plasma were found to be good materials for detecting cancer-specific DNA in the peripheral blood and the presence of KRAS mutations in blood-derived DNA may be used as a prognostic biomarker for patients with pancreatic cancer.

Ad-REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/Dkk-3 gene therapy is an attractive therapeutic tool for pancreatic cancer.

Loss or decreased expression of runt-related transcription factor 3 (RUNX3), a tumor suppressor gene involved in gastric and other cancers, has been frequently observed in hepatocellular carcinoma (HCC). The objective of this study was to identify the regulatory mechanism of the epithelial-mesenchymal transition (EMT) by RUNX3 in HCC. Human HCC cell lines, Hep3B, Huh7, HLF and SK-Hep1, were divided into low-and high-EMT lines, based on their expression of TWIST1 and SNAI2, and were used in this in vitro study. Ectopic RUNX3 expression had an anti-EMT effect in low-EMT HCC cell lines characterized by increased Ecadherin expression and decreased N-cadherin and vimentin expression. RUNX3 expression has previously been reported to reduce jagged-1 (JAG1) expression; therefore, JAG1 ligand peptide was used to reinduce EMT in RUNX3-expressing low-EMT HCC cells. Immunohistochemical analyses were performed for RUNX3, E-cadherin, N-cadherin and TWIST1 in 33 human HCC tissues, also divided into low-and high-EMT HCC, based on TWIST1 expression. E-cadherin expression was correlated positively and N-cadherin expression was correlated negatively with RUNX3 expression in low-EMT HCC tissues. Correlations between EMT markers and RUNX3 mRNA expression were analyzed using Oncomine datasets. Similarly, mRNA expression of E-cadherin was also significantly correlated with that of RUNX3 in low-EMT HCC, while mRNA expression of JAG1 was negatively correlated with that of RUNX3. These results suggest a novel mechanism by which loss or decreased expression of RUNX3 induces EMT via induction of JAG1 expression in low-EMT HCC.

Abstract. runt-related transcription factor 3 (rUnX3) is a candidate tumor suppressor gene that is downregulated in various cancers. In the present study, we analyzed the regulatory function of rUnX3 on Jagged-1 (JAg1) expression and cancer stem cell (csc) signaling in hepatocellular carcinoma (Hcc). eleven Hcc cell lines and 30 human Hcc tissues were used. rUnX3 and JAg1 expression levels were analyzed by immunoblotting and immunohistochemistry. ectopic rUnX3 expression was induced by introducing rUnX3 cDnA into the rUnX3-negative Hcc cell line Hep3B and Huh7 cells. Furthermore endogenous rUnX3 expression was knocked down by rUnX3 sirnA in sK-Hep-1 cells. In order to analyze JAg1 transcriptional regulation, we conducted reporter assays, chromatin immunoprecipitation (chIp) assays and electrophoretic mobility shift assays (eMsAs). tumorigenicity was analyzed using a scID mouse liver injection model. An inverse correlation was observed between rUnX3 expression and JAg1 expression in most Hcc cell lines and tissues. restoring rUnX3 expression decreased the expression of JAg1 in Hep3B and Huh7 cells, whereas JAg1 expression was upregulated in rUnX3 sirnA-treated sK-Hep-1 cells. reporter assays, chIp assays and eMsAs revealed that rUnX3 directly bound to the transcriptional regulatory region of JAg1 and suppressed JAg1 transcription. Moreover, rUnX3 restoration downregulated cscs by suppressing JAg1-mediated notch signaling. the tumorigenic capacity of rUnX3-expressing Hep3B cells was lower compared to that of control Hep3B cells. rUnX3 expression suppressed JAg1 expression and resulted in downregulation of tumorigenesis by suppression of JAg1-mediated cscs. IntroductionHepatocellular carcinoma (Hcc) is the third most frequent cause of cancer-related death worldwide, and its incidence rate is increasing (1-3). patients diagnosed with Hcc have a poor prognosis because of the aggressive nature of the disease (1,4). Although various therapeutic strategies have been developed, such as operation, ablation and chemotherapy, therapies to treat patients with advanced Hcc are lacking. there is an urgent need to elucidate the pathologic mechanism underlying molecular-targeted therapies in Hcc. Many studies have considered that the dysfunction of oncogenes and tumor suppressor genes, reactivation of developmental pathways, and activation of growth factors and their receptors play major roles in the development and progression of Hcc (1,5). Further, the expression of a number of tumor suppressor genes is attenuated by a combination of genetic and epigenetic events, including loss of an allele, mutation, or promoter methylation (6,7). the loss of heterozygosity (loH) on chromosome 1p36 was reported as one of the most frequent loH in Hcc (7,8). loH on chromosome 1p36 suggests the presence of important tumor suppressor genes on that chromosome. It was reported that runt-related transcription factor 3 (rUnX3), located on chromosome 1p36, correlates with tumorigenesis and progression of gastric cancer (9). rUnX3 is an apoptotic fact...