Background & Aims The incidence of hepatocellular carcinoma (HCC) increases with age, but protective antibody responses decrease with time after infants are immunized against hepatitis B virus (HBV). ...We investigated whether immunization of infants against HBV prevents their developing HCC as adults. We also searched for strategies to maximize the cancer-preventive effects. Methods We collected data from 2 Taiwan HCC registry systems on 1509 patients (6–26 years old) diagnosed with HCC from 1983 through 2011. Data on history of HBV immunization and prenatal maternal levels of HBV antigens of all HCC patients born after July 1984 were retrieved from the HBV immunization data bank of the Taiwan Center for Disease Control. We collected data on birth cohort-specific populations (6–26 years old) of Taiwan using the National Household Registry System. Rates of HCC incidence per 105 person-years were derived by dividing the number of patients with HCC by the person-years of the general population. Relative risks (RR) for HCC were estimated by Poisson regression analysis in vaccinated vs unvaccinated birth cohorts. We stratified patients by age group to evaluate the association of birth cohorts and HCC risks. Results Of the 1509 patients with HCC, 1343 were born before, and 166 were born after, the HBV vaccination program began. HCC incidence per 105 person-years was 0.92 in the unvaccinated cohort and 0.23 in the vaccinated birth cohorts. The RRs for HCC in patients 6–9 years old, 10–14 years old, 15–19 years old, and 20–26 years old who were vaccinated vs unvaccinated were 0.26 (95% confidence interval CI, 0.17–0.40), 0.34 (95% CI, 0.25–0.48), 0.37 (95% CI, 0.25–0.51), and 0.42 (95% CI, 0.32–0.56), respectively. The RR for HCC in 6- to 26-year-olds was lower in the later vs the earlier cohorts (born in 1992–2005 vs 1986–1992; P < .001 and 1986–1992 vs 1984–1986; P < .002). Transmission of HBV from highly infectious mothers and incomplete immunization were associated with development of HCC. Conclusions Based on an analysis of 1509 patients with HCC in Taiwan, immunization of infants against HBV reduces their risk of developing HCC as children and young adults. Improving HBV vaccination strategies and overcoming risk factors could reduce the incidence of liver cancer.
To examine unintentional drowning mortality by age and body of water across 60 countries, to provide a starting point for further in-depth investigations within individual countries.
The latest ...available three years of mortality data for each country were extracted from WHO Health Statistics and Information Services (updated at 13 November 2013). We calculated mortality rate of unintentional drowning by age group for each country. For countries using International Classification of Disease 10 (ICD-10) detailed 3 or 4 Character List, we further examined the body of water involved.
A huge variation in age-standardised mortality rate (deaths per 100 000 population) was noted, from 0.12 in Turkey to 9.19 in Guyana. Of the ten countries with the highest age-standardised mortality rate, six (Belarus, Lithuania, Latvia, Russia, Ukraine and Moldova) were in Eastern Europe and two (Kazakhstan and Kyrgyzstan) were in Central Asia. Some countries (Japan, Finland and Greece) had a relatively low rank in mortality rate among children aged 0-4 years, but had a high rank in mortality rate among older adults. On the contrary, South Africa and Colombia had a relatively high rank among children aged 0-4 years, but had a relatively low rank in mortality rate among older adults. With regard to body of water involved, the proportion involving a bathtub was extremely high in Japan (65%) followed by Canada (11%) and the USA (11%). Of the 13 634 drowning deaths involving bathtubs in Japan between 2009 and 2011, 12 038 (88%) were older adults aged 65 years or above. The percentage involving a swimming pool was high in the USA (18%), Australia (13%), and New Zealand (7%). The proportion involving natural water was high in Finland (93%), Panama (87%), and Lithuania (85%).
After considering the completeness of reporting and quality of classifying drowning deaths across countries, we conclude that drowning is a high-priority public health problem in Eastern Europe, Central Asia, Japan (older adults involving bathtubs), and the USA (involving swimming pools).
The expanded definition of liver-related deaths includes a wide range of etiologies and sequelae. We compared the changes in liver-related mortality by etiology and sequelae for different age groups ...between 2008 and 2018 in the USA using both underlying and multiple cause of death (UCOD and MCOD) data.
We extracted mortality data from the CDC WONDER. Both the absolute (rate difference) and relative (rate ratio and 95% confidence intervals) changes were calculated to quantify the magnitude of change using the expanded definition of liver-related mortality.
Using the expanded definition including secondary liver cancer and according to UCOD data, we identified 68,037 liver-related deaths among people aged 20 years and above in 2008 (29 per 100,000) and this increased to 90,635 in 2018 (33 per 100,000), a 13% increase from 2008 to 2018. However, according to MCOD data, the number of deaths was 113,219 (48 per 100,000) in 2008 and increased to 161,312 (58 per 100,000) in 2018, indicating a 20% increase. The increase according to MCOD was mainly due to increase in alcoholic liver disease and secondary liver cancer (liver metastasis) for each age group and hepatitis C virus (HCV) and primary liver cancer among decedents aged 65-74 years.
The direction of mortality change (increasing or decreasing) was similar in UCOD and MCOD data in most etiologies and sequelae, except secondary liver cancer. However, the extent of change differed between UCOD and MCOD data.
Abstract Clear cell renal cell carcinoma (ccRCC) is the major and aggressive subtype of RCC. Previously, we identified 383 differentially expressed genes by analyzing full-length cDNA libraries of ...ccRCC and normal kidney tissues. In this study, we applied functional network analysis to the differentially expressed genes for identifying deregulated molecular pathways in ccRCC, and the results indicated that MYC showed a prominent role in the highest scoring network. The upregulation of MYC expression was validated in ccRCC tissues and cell lines. Furthermore, Knockdown of MYC expression by MYC -specific siRNA significantly inhibited the abilities of uncontrolled proliferation, anchorage-independent growth and arrested cell cycle in the G0/G1 phase in ccRCC cells. Moreover, we found that 37 differentially expressed genes were shown to be MYC-target genes, and the upregulation of the MYC-target genes BCL2 , CCND1 , PCNA , PGK1 , and VEGFA were demonstrated. The expression of these MYC-target genes was significantly correlated with the expression of MYC in ccRCC tissues, and knockdown of MYC also suppressed the expression of these MYC-target genes in ccRCC cells. The recruitment of MYC to the promoter regions of BCL2 , CCND1 , PCNA , PGK1 , and VEGFA was shown by Chromatin immunoprecipitation assay. These results suggest that MYC pathway is activated and plays an essential role in the proliferation of ccRCC cells.
It has been observed that enlargement of perihepatic lymph nodes may be seen in patients with chronic hepatitis B, particularly during acute flares of CHB. We hypothesized that there may be a ...correlation between the nodal change patterns in CHB patients with acute flare and HBeAg status. Perihepatic lymph node sizes of 87 patients with acute flares of CHB were documented, with a median follow up of 43 months. Patients were separated into 3 groups, HBeAg-positive with HBe seroconversion (group 1), HBeAg-positive without HBe seroconversion (group 2), and HBeAg-negative (group 3). Group 1 has the highest incidence of enlarged lymph nodes (92.3%) compared with group 2 (75.8%) and group 3 (46.8%) (p = 0.003). And if nodal width at acute flare was > 8mm and interval change of nodal width was >3mm, the incidence of HBeAg seroconversion will be 75% (p<0.001).
Larger perihepatic lymph nodes are seen in CHB acute flare patients with positive HBeAg and the magnitude of nodal width change may predict HBeAg seroconversion at recovery.
HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to ...evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs).
In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS), metastasis-free survival (MeFS), urinary bladder recurrence-free survival (UBRFS), and various clinicopathological factors.
HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005). Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p < 0.0001), MeFS (p < 0.0001), and UBRFS (p = 0.0370) in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk RR = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS). Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035) and MeFS (p = 0.0015) in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis) with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015).
HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive of worse DSS and MeFS, suggesting its roles in tumorigenesis or carcinogenesis and potentiality as a prognostic marker of UTUC. High HuR cytoplasmic expression might identify patients more likely to be beneficial for adjuvant chemotherapy.
Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph ...receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression.
Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that
was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders. Immunohistochemical study was conducted to assess the EphA4 expression in pre-treatment biopsy specimens from 172 rectal cancer patients without distant metastasis. The relationships between EphA4 expression and various clinicopathological factors or survival were statistically analyzed.
EphA4 expression was significantly associated with vascular invasion (
=0.015), post-treatment depth of tumor invasion (
=0.006), pre-treatment and post-treatment lymph node metastasis (
=0.004 and
=0.011, respectively). More importantly, high EphA4 expression was significantly predictive for lesser degree of tumor regression after CCRT (
=0.031). At univariate analysis, high EphA4 expression was a negative prognosticator for disease-specific survival (
=0.0009) and metastasis-free survival (
=0.0001). At multivariate analysis, high expression of EphA4 still served as an independent adverse prognostic factor for disease-specific survival (HR, 2.528; 95% CI, 1.131-5.651;
=0.024) and metastasis-free survival (HR, 3.908; 95% CI, 1.590-9.601;
=0.003).
High expression of EphA4 predicted lesser degree of tumor regression after CCRT and served as an independent negative prognostic factor in patients with rectal cancer.
Locally advanced rectal cancers are currently treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery, but risk stratification and final outcomes remain suboptimal. In this ...study, we identify and validate targetable metabolic drivers relevant to the prognosis of patients with rectal cancer treated with CCRT. Using a published transcriptome of rectal cancers, we found that asparagine synthetase (
ASNS
) gene significantly predicted the response to CCRT. From 172 patients with rectal cancer, the expression levels of ASNS, using immunohistochemistry assays, were further evaluated in tumor specimens initially obtained by using colonoscopy. Expression levels of ASNS were further correlated with major clinicopathological features and clinical survivals in this valid cohort. ASNS deficiency was significantly related to advanced posttreatment tumor (T3, T4;
P
= .015) and nodal status (N1, N2;
P
= .004) and inferior tumor regression grade (
P
< .001). In survival analyses, ASNS deficiency was significantly associated with shorter local recurrence-free survival (LRFS;
P
= .0039), metastasis-free survival (MeFS;
P
= .0001), and disease-specific survival (DSS;
P
= .0006). Furthermore, ASNS deficiency was independently predictive of worse outcomes for MeFS (
P
= .012, hazard ratio = 3.691) and DSS (
P
= .022, hazard ratio = 2.845), using multivariate analysis. ASNS deficiency is correlated with poor therapeutic response and worse survivals in patients with rectal cancer receiving neoadjuvant CCRT. These findings indicate that ASNS is a prognostic factor with therapeutic potential for treating rectal cancer.
Residents in Taiwan are often exposed to marine microorganisms through seafood and occupational exposure. The number of reported cases of infection attributable to this organism has increased since ...the first case was reported in 1985. The increasing number of cases may be caused by greater disease activity or improved recognition by clinicians or laboratory workers. We analyze a clinical-case series of 84 patients with Vibrio vulnificus infection from 1995 to 2000 and describe the molecular epidemiologic features of pathogens isolated from these patients. The spectrum of clinical manifestations and outcomes, options of antimicrobial therapy, and virulence mechanisms were investigated. Results of molecular typing of isolates from humans and marine environment in this country had a high genetic divergence among these isolates. Education and measures are needed to prevent this emerging disease.
It is not known how many stroke patients die from fatal pulmonary complications such as aspiration pneumonia (AP) and choking each year in the United States. This study aimed to determine the ...frequency of reporting of AP or choking as a cause of death on death certificates with mention of stroke in the United States as a proxy measure of the incidence of dying from AP or choking among patients with stroke.
We used multiple-cause mortality data for the years 2001 to 2010 to identify death certificates with mention of stroke (International Classification of Diseases, Tenth Revision code I60-I69), AP (International Classification of Diseases, Tenth Revision code J69), and choking (International Classification of Diseases, Tenth Revision code W78-W80) for analysis.
Of 2 424 379 death certificates with mention of stroke in the United States between 2001 and 2010, 5.1% (n=124 503) reported AP as a cause of death, and 1.5% (n=36 997) reported choking as a cause of death. However, if we confined the analysis to autopsy-confirmed cases, the frequency decreased to 1.3% (555/42 732) and 1.3% (541/42 732), respectively. The adjusted odds ratios of reporting AP or choking as a cause of death were higher among men, increased with age, and were higher among decedents who died in a nursing home/long-term care.
The estimated incidence of dying from AP and choking among patients who died with stroke was 5% (~12 000 deaths per year) and 1% (~3700 deaths per year) according to information reported on death certificates. Efforts are needed to reduce the number of deaths from these 2 preventable complications.
PDF
