Lymph node dissection is an indispensable component of radical cystectomy for bladder cancer. Information obtained with lymph node dissection is highly predictive of patient survival, affecting ...decision‐making for adjuvant therapy (diagnostic role). Also, lymph node dissection provides survival benefits in certain patients by removing metastasized nodes (therapeutic role). However, an optimal extent of lymph node dissection has not been established yet. Data from surgical mapping studies showed that approximately 10% of the primary lymphatic landing sites were common iliac nodes, suggesting that lymph node dissection below the common iliac bifurcation is suboptimal. Several retrospective studies have shown a possible survival advantage with more extended lymph node dissection. However, the results of the first prospective randomized controlled trial failed to prove the survival advantage of extended lymph node dissection up to the level of the inferior mesenteric artery, compared with lymph node dissection below the bifurcation of the common iliac artery. Currently, lymph node dissection templates recommended by major guidelines are not consistent with each other. Furthermore, the evidence is limited in the settings of neoadjuvant chemotherapy, robot‐assisted surgery and high‐risk non‐muscle‐invasive disease. Physicians need to decide the extent of lymph node dissection for each patient, taking into account the potential survival benefit and possible harms of extended lymph node dissection. Another randomized controlled trial is currently underway and will provide further evidence shortly.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Amino acids have emerged as novel biomarkers for predicting type 2 diabetes (T2D), but the epidemiologic data linking circulating amino acid profiles with T2D are sparse in Asian populations. We ...conducted a nested case-control study within a cohort of 4,754 nondiabetic Japanese employees who attended a comprehensive health checkup in 2008-2009 and agreed to provide blood samples. During a 5-year follow-up, incident T2D cases were ascertained based on plasma glucose, glycated hemoglobin, and self-report. Two controls matched to each case on sex, age, and the date of serum sampling were randomly selected by using density sampling, resulting in 284 cases and 560 controls with amino acid measures. High concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, alanine, glutamate, ornithine, and lysine were associated with an increased risk of incident T2D, in a linear manner. High glutamine concentrations were associated with a decreased risk of incident T2D. Further adjustment for the homeostasis model assessment of insulin resistance attenuated these associations. Overall, these amino acids may be novel useful biomarkers in the identification of people at risk of T2D before overt symptoms. Insulin resistance may account for or mediate the relationship between these amino acids and risk of incident T2D.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: Although previous research has focused on the association between long working hours and several mental health outcomes, little is known about the association in relation to mental ...health-related sickness absence, which is a measure of productive loss. We aimed to investigate the association between overtime work and the incidence of long-term sickness absence (LTSA) due to mental disorders.Methods: Data came from the Japan Epidemiology Collaboration on Occupational Health Study (J-ECOH). A total of 47,422 subjects were followed-up in the period between April 2012 and March 2017. Information on LTSA was obtained via a study-specific registry. Baseline information was obtained at an annual health checkup in 2011; overtime working hours were categorized into <45; 45–79; 80–99; and ≥100 hours/month.Results: During a total follow-up period of 211,443 person-years, 536 people took LTSA due to mental disorders. A Cox proportional hazards model showed that compared to those with less than 45 hours/month of overtime work, those with 45–79 hours/month were at a lower risk of LTSA due to mental health problems (hazard ratio HR 0.63; 95% confidence interval CI, 0.56–0.71) while those with overtime work of ≥100 hours/month had a 2.11 (95% CI, 1.12–3.98) times higher risk of LTSA due to mental health problems.Conclusion: Engaging in excessive overtime work was linked with a higher risk of LTSA due to mental health problems while the lower risk observed among individuals working 45–79 hours/month of overtime work might have been due to a healthy worker effect.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Several studies suggest the involvement of dietary habits and gut microbiome in allergic diseases. However, little is known about the nutritional and gut microbial factors associated with the risk of ...allergic rhinitis (AR). We recruited 186 participants with symptoms of AR and 106 control subjects without symptoms of AR at the Hitachi Health Care Center, Japan. The habitual consumption of 42 selected nutrients were examined using the brief-type self-administered diet history questionnaire. Faecal samples were collected and subjected to amplicon sequencing of the 16S ribosomal RNA gene hypervariable regions. Association analysis revealed that four nutrients (retinol, vitamin A, cryptoxanthin, and copper) were negatively associated with AR. Among 40 genera examined, relative abundance of Prevotella and Escherichia were associated with AR. Furthermore, significant statistical interactions were observed between retinol and Prevotella. The age- and sex-adjusted odds of AR were 25-fold lower in subjects with high retinol intake and high Prevotella abundance compared to subjects with low retinol intake and low Prevotella abundance. Our data provide insights into complex interplay between dietary nutrients, gut microbiome, and the development of AR.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Physical activity has been linked to a lower risk of chronic kidney disease (CKD); however, evidence on the relationship between domain-specific physical activity and CKD is scarce. This ...study aimed to examine the risk of CKD in relation to leisure-time, occupational, and commuting physical activities in a large occupational cohort in Japan. Participants were 17,331 workers (20–65 years old) without CKD and were followed-up for a maximum period of 13 years. Incident CKD was defined as an estimated glomerular filtration rate of < 60 mL/min/1.73 m
2
and/or proteinuria determined using the dipstick test. The Cox proportional hazards models were used to examine the associations. During 147,752 person-years of follow-up, 4013 participants developed CKD. Workers who were standing or walking at work and those who were fairly active at work had adjusted hazard ratios of 0.88 (95% confidence interval 0.86–0.96) and 0.89 (95% confidence interval 0.78–1.02), respectively, for developing CKD than sedentary workers. Leisure-time physical activity and walking for commute were not associated with CKD risk. Our findings suggest that occupational, but not leisure-time and commuting physical activities, is associated with a lower CKD risk.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Although the albumin-to-globulin ratio (AGR) is a promising biomarker, no study has investigated its prognostic significance for advanced urothelial carcinoma (UC). This study conformed to ...the REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria. We retrospectively reviewed 176 patients with advanced UC treated with pembrolizumab between 2018 and 2020. We evaluated the associations between pretreatment clinicopathological variables, including the AGR and performance status (PS), with progression-free survival, cancer-specific survival, and overall survival. The Cox proportional hazards model was used for univariate and multivariable analyses. The AGR was dichotomized as < 0.95 and ≥ 0.95 based on receiver operating characteristic curve analysis. After excluding 26 cases with missing data from the total of 176 cases, 109 (73%) patients experienced disease progression, 75 (50%) died from UC, and 6 (4%) died of other causes (median survival = 12 months). Multivariate analyses identified PS ≥ 2 and pretreatment AGR < 0.95 as independent poor prognostic factors for all endpoints. Furthermore, a prognostic risk model incorporating these two variables achieved a relatively high concordance index for all endpoints. This is the first report to evaluate the significance of AGR in advanced UC. Pretreatment AGR < 0.95 may serve as a prognostic marker for advanced UC treated with pembrolizumab.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Molecular targeted therapy using poly (ADP-ribose) polymerase inhibitors has improved survival in patients with castration-resistant prostate cancer (CRPC). However, this approach is only effective ...in patients with specific genetic mutations, and additional drug discovery targeting epigenetic modulators is required. Here, we evaluated the involvement of the transcriptional coregulator ESS2 in prostate cancer. ESS2-knockdown PC3 cells dramatically inhibited proliferation in tumor xenografts in nude mice. Microarray analysis revealed that ESS2 regulated mRNA levels of chromodomain helicase DNA binding protein 1 (CHD1)-related genes and other cancer-related genes, such as PPAR-γ, WNT5A, and TGF-β, in prostate cancer. ESS2 knockdown reduced nuclear factor (NF)-κB/CHD1 recruitment and histone H3K36me3 levels on the promoters of target genes (TNF and CCL2). In addition, we found that the transcriptional activities of NF-κB, NFAT and SMAD2/3 were enhanced by ESS2. Tamoxifen-inducible Ess2-knockout mice showed delayed prostate development with hypoplasia and disruption of luminal cells in the ventral prostate. Overall, these findings identified ESS2 acts as a transcriptional coregulator in prostate cancer and ESS2 can be novel epigenetic therapeutic target for CRPC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A cohort study to assess LDCT screening for lung cancer targeting the general population demonstrated a reduction in lung cancer mortality and estimated the proportion of overdiagnosis.
Abstract
...Objectives
To evaluate the effectiveness of lung cancer screening using low-dose computed tomography for the general population, we conducted a retrospective cohort study of screening for participants among Hitachi residents.
Materials and Methods
Citizens aged 50–74 who underwent low-dose computed tomography screening at least once during 1998–2006 were defined as the computed tomography group, and those who underwent X-ray screening at least once during the same period, but did not receive low-dose computed tomography screening throughout the follow-up period, were defined as the XP group. We investigated the lung cancer incidence rate, mortality rate and all-cause mortality rate for both groups from the first lung cancer screening to the end of 2012.
Results
In the computed tomography group (17 935 residents; 9790 males and 8145 females), 273 cases of lung cancer (1.5%), 72 cases of lung cancer death (0.4%), and 885 cases of all-cause death (4.9%) were observed. On the other hand, 164 cases (1.1%) of lung cancer, 80 cases (0.5%) of lung cancer death and 1188 cases (7.6%) of all-cause death were observed in the XP group (15 548 residents; 6526 males and 9022 females). The hazard ratios of the computed tomography group to the XP group adjusted for gender, age and smoking history were 1.23 for lung cancer incidence rate, 0.49 for lung cancer mortality rate and 0.57 for all-cause mortality rate. Non-smokers and light smokers (<30 pack-years) had a significantly lower lung cancer mortality (0.41 and 0.21, respectively).
Conclusion
low-dose computed tomography screening for a population including non-smokers and light smokers may be effective.
Background: While it is essential to understand how long is sufficient for return-to-work when designing paid sick-leave systems, little attempt has been done to collect cause-specific information on ...when and how many of sickness absentees returned to work, became unemployed, or passed away.Methods: We studied the first sick-leave episode of ≥30 consecutive days in those ≤55 years of age during 2012–2013 among employees of 11 Japanese private companies (n = 1,209), which were followed until 2017. Overall and disease-specific cumulative incidences of return-to-work, resignations, and deaths were estimated using competing risk analysis.Results: During the 3.5-year period (follow-up rate: 99.9%), 1,014 returned to work, 167 became unemployed, and 27 died. Overall, return-to-work occurred within 1 year in 74.9% of all absentees and in 89.3% of those who successfully returned to work. Resignation occurred within 1 year in 8.7% of all absentees and in 62.9% of all subjects who resigned. According to ICD-10 chapters, the cumulative incidence of return-to-work ranged from 82.1% for mental disorders (F00–F99) to 95.3% for circulatory diseases (I00–I99). The cumulative incidence of return-to-work due to mental disorders ranged from 66.7% in schizophrenia (F20) to 95.8% in bipolar affective disorders (F31). Death was rarely observed except for cases of neoplasms (C00–D48), of which the cumulative incidence of death reached 14.2% by 1.5 years.Conclusion: Return-to-work and resignations occurred commonly within 1 year of sick leave among long-term sickness absentees in the Japanese private companies. Our findings may assist occupational physicians and employers in developing effective social protection schemes.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Abstract
This study compared the time profile of FEV
1
after COPD diagnosis among rapid decliners, slow decliners, and sustainers in the year of COPD diagnosis. COPD subjects were identified from the ...annual medical checkup records of Hitachi, Ltd., employees in Japan (April 1998-March 2019). Subjects were categorized into 3 groups (rapid decliner decrease of FEV
1
≥ 63 mL/year, slow decliner < 63 and ≥ 31 mL/year, and sustainer < 31 mL/year) for 5 years. The time profile of FEV
1
was compared using mixed-effects model for 5 years after diagnosis; risk factors of rapid decliner were detected using logistic model/gradient boosting decision tree. Of 1294 eligible subjects, 18.6%, 25.7%, and 55.7% were classified as rapid decliners, slow decliners, and sustainers, respectively. The annual rates of FEV
1
decline were similar 3 years before and until COPD diagnosis. The mean FEV
1
in rapid decliners was 2.82 ± 0.04 L in year 0 and 2.41 ± 0.05 L in year 5, and in sustainers, it was 2.67 ± 0.02 L and 2.72 ± 0.02 L (year 0, p = 0.0004). In conclusion, FEV
1
declined yearly before diagnosis and the time profiles of FEV
1
were different in the 3 groups after COPD diagnosis. Therefore, appropriate treatment of the 3 groups with regular lung function tests is necessary to follow FEV
1
decline after COPD onset.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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