MR elastography of the liver: comparison of three measurement methods.

AIM: To analyse the inter- and intra-observer agreement of liver stiffness value (LSV) using three methods with 3 T magnetic resonance elastography (MRE) and to investigate factors related to LSV difference. MATERIALS AND METHODS: This retrospective study included 147 patients. Two independent observers measured the LSV using three region of interest (ROI) methods: (1) circular ROI with a radius of 1 cm in the right lobe, (2) largest ROI possible, and (3) average value considering the measurement area. The agreement and factors related to difference of LSV were investigated. RESULTS: The intraclass correlation coefficients were excellent at 0.982-0.997 in all methods. The differences between observers for method 1 were significantly larger than those of method 2 or method 3 (p<0.001). The Child-Pugh classification was only related to LSV difference (p<0.001). CONCLUSION: Methods 2 and 3 were significantly more reliable than method 1. The Child-Pugh classification was only related to difference of LSV.

Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.

BACKGROUND: Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. METHODS: This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. RESULTS: Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). CONCLUSIONS: Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed.

Characterization of DDRI-18 (3,3'-(1H,3'H-5,5'-bibenzo[d]imidazole-2,2'-diyl)dianiline), a novel small molecule inhibitor modulating the DNA damage response.

BACKGROUND AND PURPOSE: Recently, the DNA damage response (DDR) has emerged as a promising target for anticancer drug development. In our previous study, we identified several DDR-inhibiting compounds via high-content screening of a small molecule library using γH2AX foci as a biomarker. Here, we studied the effects of the DNA damage response inhibitor DDRI-18 (3,3'-(1H,3'H-5,5'-bibenzo[d]imidazole-2,2'-diyl)dianiline) on DDR. EXPERIMENTAL APPROACH: Osteosarcoma U2OS cells were treated with etoposide to induce DDR. The nuclear foci of γH2AX and other signalling molecules in DDR were visualized by immunofluorescence and quantified using an IN Cell Analyzer. The DNA repair capacity of cells was analysed using the comet assay and in vivo DNA end-joining assay. Cell survival after drug treatment was quantified using the MTT assay, and apoptotic cell death was analysed by Annexin V staining and flow cytometry. KEY RESULTS: DDRI-18 inhibited the non-homologous end-joining (NHEJ) DNA repair process and delayed the resolution of DNA damage-related proteins (γH2AX, ATM and BRCA1) from DNA lesions at a later phase of DDR. Furthermore, DDRI-18 enhanced the cytotoxic effects of anticancer DNA-damaging drugs, including etoposide, camptothecin, doxorubicin and bleomycin. This synergistic effect on cell death was shown to be due to caspase-dependent apoptosis. CONCLUSIONS AND IMPLICATIONS: We identified a chemical compound, DDRI-18, that has chemosensitization activity. Although the target molecule and mechanism of action of DDRI-18 remain unknown, DDRI-18 is an effective chemosensitizing agent and may improve the therapy with classical anticancer drugs.

Carbohydrate but not fat is associated with elevated aminotransferases.

BACKGROUND: Recently, many studies reported that high carbohydrate and simple sugar intake increase a risk of obesity and metabolic syndrome significantly. AIM: To investigate the effect of carbohydrate on aminotransferase levels in Korea, where the proportion of carbohydrate in meals is extremely high but fat is low. METHODS: We used the data of Korean National Health and Nutrition Examination Surveys (KNHANES). A total of 19 749 people were included. Amounts and types of consumed foods were examined by the 24 h recall method. RESULTS: Mean carbohydrate and fat proportions in total energy intake were 67.7% and 17.4%, respectively. Aminotransferase activity increased according to the rise of the proportion of carbohydrate in the energy intake. A high carbohydrate intake (>70% of energy) was associated with abnormal aminotransferase activity and metabolic syndrome. After adjusting for covariates, such as age, energy intake and body mass index, abnormal aminotransferase activity was significantly associated with carbohydrate proportion. There was a negative correlation between fat proportion in the total energy intake and aminotransferase activity (P < 0.01). The relation between aminotransferase activity and carbohydrate composition showed a J-shaped curve. The lowest point (the J point) was located at 50-60% carbohydrate. CONCLUSIONS: The proportion of carbohydrate in energy intake but not fat is positively correlated with abnormal aminotransferase activity in Koreans. This finding may be useful in planning a strategy of nutrition education for NAFLD in countries where the proportion of carbohydrate in most meals is extremely high.

Combination chemotherapy of oral 5'-deoxy-5-fluorouridine and cisplatin in advanced gastric cancer: a phase II study.

This study was designed to test the activity and feasibility of 5'-deoxy-5-fluorouridine (5'-DFUR) and cisplatin combination therapy in the treatment of advanced gastric cancer. Nineteen patients with inoperable and/or metastatic gastric cancer, which was histologically proven, were orally administered 5'-DFUR 1,200 mg/m2 on days 1 to 4 and days 15-18 combined with 70 mg/m2 of cisplatin being repeated every 4 weeks. Five partial responses (PRs) were achieved. Seven patients had stable disease and 6 progressed on therapy. The overall response rate was 27.7% (95% confidence interval: 9.69% to 53.5%). The median survival duration of all 18 patients was 25 weeks (9-64). The majority of patients had WHO grade I/II toxicity, but there was no treatment-related death. These data support that the combinations of oral 5'-DFUR and cisplatin are well tolerable and have a moderate activity with low toxicity in the treatment of advanced gastric cancer.