Clinicopathological Characteristics in Combined Hepatocellular-Cholangiocarcinoma: A Single Center Study in Korea

PURPOSE: Combined hepatocellular-cholangiocarcinoma (CHCC) is an uncommon form of cancer, and its clinicopathological features have rarely been reported in detail. This study was undertaken to evaluate the clinicopathological characteristics and prognostic factors of CHCC. MATERIALS AND METHODS: The clinicopathological features of patients diagnosed with CHCC at Severance Hospital between January 1996 and December 2007 were retrospectively studied by comparing them with the features of patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC) who had undergone a hepatic resection during the same period. RESULTS: Forty-three patients diagnosed with CHCC were included in this study (M : F=35 : 8, median age, 55 years). According to the parameters of the American Joint Committee on Cancer staging, there were 6 (14.0%), 9 (20.9%), 25 (58.1%), and 3 (7.0%) patients with stages I, II, III, and IV cancer, respectively. Thirty-two of the 43 patients underwent resection with curative intent. After resection, 27 patients (84.4%) had tumor recurrence during the follow-up period of 18 months (range: 6-106 months), and the median time to recurrence was 13 months. Overall median survival periods after hepatic resection of CHCC, HCC and CC were 34, 103 and 38.9 months, respectively (p<0.001). The median overall survival for all patients with CHCC was 21 months, and the 5-year survival rate was 18.1%. The presence of portal vein thrombosis and distant metastasis were independent prognostic factors of poor survival. CONCLUSION: Even after curative hepatic resection, the presence of a cholangiocellular component appeared to be a poor prognostic indicator in patients with primary liver cancer.ope

The Efficacy of Hepatic Resection after Neoadjuvant Transarterial Chemoembolization (TACE) and Radiation Therapy in Hepatocellular Carcinoma Greater Than 5 cm in Size

In cases of large hepatocellular carcinoma (HCC), neoadjuvant treatment such as transarterial chemoembolization (TACE) and radiation therapy can be performed. The aim of this study was to evaluate the outcome of these treatments prior to hepatic resection. Between January 1994 and May 2007, 16 patients with HCC greater than 5 cm in size were treated with TACE and radiation therapy prior to hepatic resection. The clinicopathologic factors were reviewed retrospectively. Of the 16 patients, there were 14 men and two women, and the median age was 52.5 yr. TACE was performed three times in average, and the median radiation dosage was 45 Gy. The median diameter of tumor on specimen was 9.0 cm. The degree of tumor necrosis was more than 90% in 14 patients. The median survival time was 13.3 months. Five patients had survived more than 2 yr and there were two patients who had survived more than 5 yr. Although the prognosis of large HCC treated with neoadjuvant therapy is not satisfactory, some showed long-term survival loger than 5 yr. Further research will be required to examine the survival and disease control effect in a prospective randomized study

Genome-Wide Association Study Confirming Association of HLA-DP with Protection against Chronic Hepatitis B and Viral Clearance in Japanese and Korean

Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85–90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with Pmeta = 1.89×10−12 for rs3077 and Pmeta = 9.69×10−10 for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (Pmeta = 4.40×10−19 for rs3077 and Pmeta = 1.28×10−15 for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule

Asymmetric Domino Multicatalysis for the Synthesis of 3‑Substituted Phthalides: Cinchonine/NHC Cooperative System

It is demonstrated that two organocatalysts, achiral NHC and chiral bifunctional cinchonine, are mutually compatible and operating concurrently and effectively to promote the asymmetric domino oxidation/oxa-Michael addition reaction. This protocol allowed access to both enantiomers of a product by using two natural, inexpensive pseudoenantiomeric cinchona alkaloids, cinchonine and cinchonidine, as well as to phthalides containing a chiral quaternary carbon center in good enantioselectivities

Impact of Hepatitis B Virus (HBV) X Gene Mutations on Hepatocellular Carcinoma Development in Chronic HBV Infection ▿

The hepatitis B virus (HBV) PreS mutations C1653T, T1753V, and A1762T/G1764A were reported as a strong risk factor of hepatocellular carcinoma (HCC) in a meta-analysis. HBV core promoter overlaps partially with HBx coding sequence, so the nucleotide 1762 and 1764 mutations induce HBV X protein (HBx) 130 and 131 substitutions. We sought to elucidate the impact of HBx mutations on HCC development. Chronically HBV-infected patients were enrolled in this study: 42 chronic hepatitis B (CHB) patients, 23 liver cirrhosis (LC) patients, and 31 HCC patients. Direct sequencing showed HBx131, HBx130, HBx5, HBx94, and HBx38 amino acid mutations were common in HCC patients. Of various mutations, HBx130+HBx131 (double) mutations and HBx5+HBx130+HBx131 (triple) mutations were significantly high in HCC patients. Double and triple mutations increased the risk for HCC by 3.75-fold (95% confidence interval [CI] = 1.101 to 12.768, P = 0.033) and 5.34-fold (95% CI = 1.65 to 17.309, P = 0.005), respectively, when HCC patients were compared to CHB patients. Functionally, there were significantly higher levels of NF-κB activity in cells with the HBx5 mutant and with the double mutants than that of wild-type cells and the triple-mutant cells. The triple mutation did not increase NF-κB activity. Other regulatory pathways seem to exist for NF-κB activation. In conclusion, a specific HBx mutation may contribute to HCC development by activating NF-κB activity. The HBx5 mutation in genotype C2 HBV appears to be a risk factor for the development of HCC and may be used to predict the clinical outcomes of patients with chronic HBV infection

New Automated Hepatitis C Virus (HCV) Core Antigen Assay as an Alternative to Real-Time PCR for HCV RNA Quantification▿ †

An automated hepatitis C virus (HCV) antigen (Ag) assay was evaluated with clinical samples. Determination of HCV Ag and RNA levels in 282 subjects using Abbott HCV Ag and Roche Cobas TaqMan assays revealed that these two tests were highly correlated (r = 0.9464). Thus, the HCV Ag assay could be an alternative test to quantitative reverse transcription-PCR

Effect of increased load of high-strength food wastewater in thermophilic and mesophilic anaerobic co-digestion of waste activated sludge on bacterial community structure

In recent years, anaerobic co-digestion (AcoD) has been widely used to improve reactor performance, especially methane production. In this study, we applied two different operating temperatures (thermophilic and mesophilic) and gradually increased the load of food wastewater (FWW) to investigate the bacterial communities during the AcoD of waste activated sludge (WAS) and FWW. As the load of FWW was increased, methane production rate (MPR; L CH4/Ld) and methane content (%) in both Thermophilic AcoD (TAcoD) and Mesophilic AcoD (MAcoD) increased significantly; the highest MPR and methane content in TAcoD (1.423 L CH4/L d and 68.24%) and MAcoD (1.233 L CH4/L d and 65.21%) were observed when the FWW mixing ratio was 75%. However, MPR and methane yield in both reactors decreased markedly and methane production in TAcoD ceased completely when only FWW was fed into the reactor, resulting from acidification of the reactor caused by accumulation of organic acids. Pyrosequencing analysis revealed a decrease in bacterial diversity in TAcoD and a markedly different composition of bacterial communities between TAcoD and MAcoD with an increase in FWW load. For example, Bacterial members belonging to two genera Petrotoga (assigned to phylum Thermotogae) and Petrimonas (assigned to phylum Bacteroidetes) became dominant in TAcoD and MAcoD with an increase in FWW load, respectively. In addition, quantitative real-time PCR (qPCR) results showed higher bacterial and archaeal populations (expressed as 16S rRNA gene concentration) in TAcoD than MAcoD with an increase in FWW load and showed maximum population when the FWW mixing ratio was 75% in both reactors. Collectively, this study demonstrated the dynamics of key bacterial communities in TAcoD and MAcoD, which were highly affected by the load of FWW. (C) 2016 Published by Elsevier Ltd.11sciescopu