Factors associated with ethnical disparity in overall survival for patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is an important cause of cancer-related death worldwide. Ethnical disparity in overall survival has been demonstrated for HCC patients in the United States (U.S.). We aimed to evaluate the contributors to this survival disparity. The SEER database was used to identify HCC patients from 2004 to 2012. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate overall survival by ethnicity and the contributors to ethnical survival disparity. A total of 33 062 patients were included: 15 986 Non-Hispanic Whites, 6535 Hispanic Whites, 4842 African Americans, and 5699 Asians. Compared to Non-Hispanic Whites, African Americans had worse survival (HR, 1.18; 95%CI, 1.14-1.23), while Asians had a better survival (HR, 0.85; 95%CI, 0.82-0.89), and Hispanic Whites had a similar survival (HR, 1.01; 95%CI, 0.97-1.05). Multivariate Cox analysis identified that tumor presentation- and treatment-related factors significantly contributed to the ethnical survival disparity. Especially, tumor size was the most important contributor (HR, 1.11; 95%CI, 1.07-1.16). There is no ethnical survival disparity in patients undergoing liver transplantation and sub-analysis of patients within the Milan criteria for liver transplantation demonstrated no significant survival disparity between African Americans and non-Hispanic Whites in transplantation adjustment analysis (HR, 1.23; 95%CI, 1.11-1.35 in non-adjustment analysis to HR, 1.05; 95%CI, 0.95-1.15 after adjustment). Finally, no important contributor to the superior overall survival in Asians was identified. In conclusion, poor tumor presentation at diagnosis, limited benefit from resection and restricted utilization of liver transplantation are important contributors to poorer survival of African Americans with HCC.

The global burden of hepatitis E outbreaks: a systematic review.

Hepatitis E virus (HEV) is responsible for repeated water-borne outbreaks since the past century, representing an emerging issue in public health. However, the global burden of HEV outbreak has not been comprehensively described. We performed a systematic review of confirmed HEV outbreaks based on published literatures. HEV outbreaks have mainly been reported from Asian and African countries, and only a few from European and American countries. India represents a country with the highest number of reported HEV outbreaks. HEV genotypes 1 and 2 were responsible for most of the large outbreaks in developing countries. During the outbreaks in developing countries, a significantly higher case fatality rate was observed in pregnant women. In fact, outbreaks have occurred both in open and closed populations. The control measures mainly depend upon improvement of sanitation and hygiene. This study highlights that HEV outbreak is not new, yet it is a continuous global health problem.

Cost-Effectiveness of Cetuximab for Advanced Esophageal Squamous Cell Carcinoma.

BACKGROUND: Costly biologicals in palliative oncology are emerging at a rapid pace. For example, in patients with advanced esophageal squamous cell carcinoma addition of cetuximab to a palliative chemotherapy regimen appears to improve survival. However, it simultaneously results in higher costs. We aimed to determine the incremental cost-effectiveness ratio of adding cetuximab to first-line chemotherapeutic treatment of patients with advanced esophageal squamous cell carcinoma, based on data from a randomized controlled phase II trial. METHODS: A cost effectiveness analysis model was applied based on individual patient data. It included only direct medical costs from the health-care perspective. Quality-adjusted life-years and incremental cost-effectiveness ratios were calculated. Sensitivity analysis was performed by a Monte Carlo analysis. RESULTS: Adding cetuximab to a cisplatin-5-fluorouracil first-line regimen for advanced esophageal squamous cell carcinoma resulted in an the incremental cost-effectiveness ratio of €252,203 per quality-adjusted life-year. Sensitivity analysis shows that there is a chance of less than 0.001 that the incremental cost-effectiveness ratio will be less than a maximum willingness to pay threshold of €40,000 per quality-adjusted life-year, which is representative for the threshold used in The Netherlands and other developed countries. CONCLUSIONS: Addition of cetuximab to a cisplatin-5-fluorouracil first-line regimen for advanced esophageal squamous cell carcinoma is not cost-effective when appraised according to currently accepted criteria. Cost-effectiveness analyses using outcome data from early clinical trials (i.c. a phase II trial) enable pharmaceutical companies and policy makers to gain early insight into whether a new drug meets the current eligibility standards for reimbursement and thereby potential admittance for use in regular clinical practice.

Epidemiology and management of chronic hepatitis E infection in solid organ transplantation: a comprehensive literature review.

Hepatitis E virus (HEV) infection has emerged as a global public health issue. Although it often causes an acute and self-limiting infection with low mortality rates in the western world, it bears a high risk of developing chronic hepatitis in immunocompromised patients with substantial mortality rates. Organ transplant recipients who receive immunosuppressive medication to prevent rejection are thought to be the main population at risk for chronic hepatitis E. Therefore, there is an urgent need to properly evaluate the clinical impact of HEV in these patients. This article aims to review the prevalence, infection course, and management of HEV infection after solid organ transplantation by performing a comprehensive literature review. In addition, an in-depth emphasis of this clinical issue and a discussion of future development are also presented.

Assessment of chromosomal gains as compared to DNA content changes is more useful to detect dysplasia in Barrett's esophagus brush cytology specimens.

Abnormal DNA ploidy status has been suggested as a prognostic factor for Barrett's esophagus progression into esophageal adenocarcinoma (EAC). The aim of the study was to compare image cytometry DNA analysis (ICDA) and fluorescent in situ hybridization (FISH) in the assessment of DNA ploidy status in Barrett's esophagus (BE), and to determine the value of these abnormalities as an adjunct to conventional cytology in detection of dysplasia and EAC. Brush cytology specimens of 90 BE patients were examined using ICDA and FISH with peri-centromeric probes for chromosomes 7 and 17. The results of ICDA and FISH were compared with each other, and with dysplasia grade or EAC as determined by histology and cytology. FISH and ICDA detected abnormalities in 41% (37/90) and 22% (19/90) of the BE cases, respectively. Gains of chromosome 7 and/or 17 were present in 13% of nondysplasia cases, which further increased with dysplasia stage, while overall DNA content aneuploidy was detected predominantly in high grade dysplasia (HGD) and EAC. Using FISH results combined with cytology, we were able to identify IND/LGD (indefinite/ low grade dysplasia) with a sensitivity and specificity of 75 and 76%, respectively. FISH alone detected HGD/EAC with a high sensitivity and specificity of 85 and 84%, which was superior to that of cytology alone. Thus, FISH is more sensitive than ICDA to detect chromosomal abnormalities in BE brush cytology specimens. FISH detects chromosomal gains in early stages of BE and represents a valuable adjunct to conventional cytology to detect dysplasia or EAC.

Efficient automated assessment of genetic abnormalities detected by fluorescence in situ hybridization on brush cytology in a Barrett esophagus surveillance population.

BACKGROUND: Automated assessment of genetic abnormalities detected by fluorescence in situ hybridization (FISH) in brush cytology specimens from patients with Barrett esophagus (BE) may enhance the clinical applicability of this methodology. The objectives of this study were to validate a novel, automated, proprietary system (CytoVison SPOT AX) for the assessment of FISH abnormalities in BE brush cytology and, subsequently, to use this automated method for screening of a BE surveillance cohort. METHODS: FISH with DNA probes for chromosomes 9, 17, and Y, and for the 9p21 (p16), 17q11.2 (Her2/neu), and 17p13.1 (p53) loci was applied on brush cytology specimens from a surveillance cohort of 151 patients with BE. Validation of the automated system was performed by comparison of the automated FISH results with manual scores for the first 60 patients. RESULTS: There was 98% concordance between manual and automated FISH analysis with kappa values from 0.49 to 1 for the different probes. The loss of 17p13.1 (p53) was observed in only 5% of patients with no dysplasia (ND) and in 9% of patients with low-grade dysplasia (LGD) but increased to 46% in patients with high-grade dysplasia (HGD) (P < .005; Fisher exact test). Chromosomes 9 and 17 were observed in 6% of patients with ND, in 21% of patients with LGD, and in 62% of patients with HGD (P < .05). Ten percent of patients with ND had loss of the Y chromosome, which increased to 27% in patients with HGD (P< .05). The amplification of 17q11.2 (Her2/neu) was detected in 62% of patients with HGD (P < .001). CONCLUSIONS: The current investigation indicated that the CytoVison SPOT AX is an objective, efficient system for the analysis of DNA-FISH on BE brush cytology and is applicable for analyzing large populations of BE patients. In the current study cohort, the loss of 17p13.1 (p53), Y chromosome loss, and polysomy of chromosomes 17 and 9 were correlated with increasing grade of dysplasia in patients with BE.