Average lifespan shortened due to cancer in selected countries of North America, Europe, Asia and Oceania, 2006 and 2016.

PURPOSE: We applied a novel measure of average lifespan shortened (ALSS) to examine changes in lifespan among patients who died of cancer over a 10-year period from 2006 to 2016 in 20 selected high-income countries from North America, Europe, Asia, and Oceania. METHODS: We retrieved cancer deaths in each country from the World Health Organization mortality database. We calculated ALSS as a ratio of years of life lost to the expected lifespan among patients who died from cancer. RESULTS: Between 2006 and 2016, we observed modest changes in ALSS for overall cancer deaths over the study in many countries. The changes in the ALSS over time due to any cancer ranged between -1.7 and +0.4 percentage points (pps) among men and between -1.9 and +0.6 pps among women. Across countries, overall cancer deaths led to an average loss between 16% and 22% of their lifespan in men, and between 18% and 24% in women. Across cancer sites, patients who died of central nervous system cancers, for instance, lost a large proportion of their lifespan. CONCLUSIONS: In this study, we demonstrated the use of ALSS across selected high-income countries, which enables population-level assessment of premature mortality among cancer patients over time.

Relationship between haematological data and radiation doses of TEPCO workers before and after the FDNNP accident.

We evaluated the correlation between radiation dose and the medical examination data of Tokyo Electric Power Company Holdings, Inc (TEPCO) employees working during the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in 2011. This study included 2164 male TEPCO workers who received periodic medical examinations from March 2006 to January 2013. First, we conducted log-linear regression analyses using the haematological data of 585 emergency workers and confounding factors to examine the effect of internal radiation exposure in March 2011. Since external radiation exposure was a major influence, we then evaluated the correlation between both internal and external radiation dose and the haematological data of 1801 emergency workers and confounding factors before and after the accident. Among 585 workers, internal radiation exposure in March 2011 alone was mainly due to thyroid doses (0.1-10 Gy) but not to bone marrow (BM) doses (0.01-1 mGy). Compared to before and after the accident, we found that the levels of monocytes, eosinophils (Eos) and basophils increased slightly, whereas the frequency of smoking and alcohol consumption decreased substantially. External dose exposure was positively correlated with haemoglobin (Hb), red blood cell and Eos but negatively correlated with age, haematocrit and frequency of alcohol consumption. Among these variables, Hb exhibited the strongest correlation with external dose. Regarding the correlation with Hb, although there is a possibility that confounding factors other than exposure were not evaluated, our findings on emergency workers can serve as a reference for the evaluation of health conditions during the emergency period of future nuclear-related accidents.

Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer: a collaborative analysis of 20 prospective studies and Mendelian randomization analysis.

BACKGROUND: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. METHODS: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. RESULTS: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. CONCLUSIONS: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.

Must countries shoulder the burden of mesothelioma to ban asbestos? A global assessment.

INTRODUCTION: Mesothelioma is a key asbestos-related disease (ARD) but can be difficult to diagnose. Countries presumably ban asbestos to reduce future ARD burdens, but it is unknown if countries ban asbestos as a consequence of ARD burdens. We assessed if and to what extent mesothelioma burden has an impact on a country banning asbestos and obtaining targets for preventative strategies. METHODS: We analysed the status of asbestos ban and mesothelioma burden during 1990-2019 in 198 countries. We assessed mesothelioma burden by age-adjusted mortality rates (MRs) estimated by the Global Burden of Disease Study (GBD) and mesothelioma identification by the WHO mortality database. For GBD-estimated mesothelioma MR, the pre-ban period in the asbestos-banned countries was compared with the 1990-2019 period in the not-banned countries. For mesothelioma identification, the 1990-2019 period was applied to both banned and not-banned countries. RESULTS: The association of mesothelioma MR with ban status increased as the ban year approached. Logistic regression analyses showed that the odds of a country banning asbestos increased 14.1-fold (95% CI 5.3 to 37.9) for mesothelioma identification combined with a 26% (12% to 42%) increase per unit increase of mesothelioma MR (one death per million per year) during the period 1-5 year before ban (model p<0.0001). CONCLUSION: Mesothelioma burden had an impact on, and together with its identification, explained the banning of asbestos in many countries. Asbestos-banned countries likely learnt lessons from their historical policies of using asbestos because mesothelioma burden and identification follow historical asbestos use. Prevention targets for ARD elimination should combine asbestos ban with mesothelioma identification.

Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia.

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet  = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.

Average lifespan shortened due to Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, and leukemia in Japan, 1990-2015.

We examined whether there were gains in lifespan among patients who died from hematological cancers in Japan between 1990 and 2015 using the novel average lifespan shortened (ALSS) measure. We obtained mortality data from the World Health Organization mortality database. Years of life lost (YLL) was calculated using Japanese life tables. ALSS measure was calculated as a ratio of YLL to the expected lifespan. The ALSS results showed that the lifespan of patients who died from hematological cancers has improved over time. For instance, women who died of leukemia in 1990 lost about 34% of their lifespan; conversely, those who died in 2015 lost about 20%. Likewise, men dying from non-Hodgkin lymphoma lost about 22% of their lifespan in 1990, whereas men lost about 14% in 2015. In summary, the new ALSS measure shows prolonged lifespans among patients who died from hematological cancers in Japan over the study period.

Mass Screening of SARS-CoV-2 Variants using Sanger Sequencing Strategy in Hiroshima, Japan.

This study aimed to develop the feasible and effective universal screening strategy of the notable SARS-CoV-2 variants by Sanger Sequencing Strategy and then practically applied it for mass screening in Hiroshima, Japan. A total of 734 samples from COVID-19 confirmed cases in Hiroshima were screened for the notable SARS-CoV-2 variants (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.1, C.37, B.1.1.529, etc.). The targeted spike region is amplified by nested RT-PCR using in-house designed primer set hCoV-Spike-A and standard amplification protocol. Additionally, randomly selected 96 samples were also amplified using primer sets hCoV-Spike-B and hCoV-Spike-C. The negative amplified samples were repeated for second attempt of amplification by volume-up protocol. Thereafter, the amplified products were assigned for Sanger sequencing using corresponding primers. The positive amplification rate of primer set hCoV-Spike-A, hCoV-Spike-B and hCoV-Spike-C were 87.3%, 83.3% and 93.8% respectively for standard protocol and increased to 99.6%, 95.8% and 96.9% after second attempt by volume-up protocol. The readiness of genome sequences was 96.9%, 100% and 100% respectively. Among 48 mutant isolates, 26 were B.1.1.7 (Alpha), 7 were E484K single mutation and the rest were other types of mutation. Moreover, 5 cluster cases with single mutation at N501S were firstly reported in Hiroshima. This study indicates the reliability and effectiveness of Sanger sequencing to screen large number of samples for the notable SARS-CoV-2 variants. Compared to the Next Generation Sequencing (NGS), our method introduces the feasible, universally applicable, and practically useful tool for identification of the emerging variants with less expensive and time consuming especially in those countries where the NGS is not practically available. Our method allows not only to identify the pre-existing variants but also to examine other rare type of mutation or newly emerged variants and is crucial for prevention and control of pandemic.

Perception of feeling cold in the bedroom and sleep quality.

Sleep disorders are drawing the attention of both medical and public health concern worldwide. In Japan, research suggests that one fifth of adults do not receive appropriate sleep and 40% of adults sleep less than 6 hours a day, and sleep rates are decreasing further year by year. Many studies show that cold indoor environments negatively affect sleep comfort and quality. Whereas these studies have focused on the effects of low bedroom temperature, few studies have focused on the effect of perception of coldness. Indoor temperature is typically much lower in Japan than in other countries. Therefore, the current study aimed to identify the effect of perception of bedroom coldness on sleep quality among Japanese adults. After controlling for covariates of age, presence of current disease and pain, smoking and consumption of alcohol (Model 1), participants who sometimes, often or always felt cold in the bedroom exhibited 0.57 (95% CI=0.32-0.83, p=<.0001), 1.08 (95% CI=0.82-1.35, p<.0001) or 2.25 (95% CI=1.83-2.67, p<.0001) higher PSQI scores compared to the group which didn't feel cold in bedroom. Our findings suggest keeping the bedroom thermal environment above a minimum limit as recommended by the World Health Organization or other organization during colder, winter nights when feeling cold during sleep. Additional deficiencies in the housing infrastructure, air quality issues due to the use of a heater, and micro bed environment need to be holistically addressed. Sleep quality can be improved by certain level via providing thermally comfortable sleeping environment.

Dairy products and the risk of developing prostate cancer: A large-scale cohort study (JACC Study) in Japan.

Dairy products have been indicated as a risk factor for prostate cancer. However, only a few epidemiological studies have reported dairy products as being a risk factor for prostate cancer in Japan, reporting contradictory results. We therefore investigated the association between the intake of dairy products and the occurrence of prostate cancer through a large-scale cohort study. The Japan Collaborative Cohort study analyzed approximately 110,000 residents from various Japanese districts who participated in our questionnaire survey during 1988-1990. The subjects of the present study were 26,464 men (age range: 40-79 years) from 24 districts wherein cancer incidence was reported. Their clinical course was followed up until 2009. Hazard ratios (HRs) were calculated using Cox's proportional hazards model, adjusted for age, survey area, family history of prostate cancer, body mass index, and total energy intake. For diet, we calculated the HRs associated with intermediate and high consumption of dairy products and compared them with those associated with low consumption. There were 412 cases of prostate cancer in the survey population. As dairy products, milk, yogurt, cheese, and butter were evaluated. Among them, milk consumption was associated with a significant risk (HR = 1.37, p = 0.009) and a dose-dependent response (p for trend = 0.009) adjusted for age and family history of prostate cancer, stratified by area. Milk and yogurt consumption showed a significantly positive risk and a dose-response relationship adjusted for age, family history of prostate cancer, body mass index, and total energy intake, stratified by area. In summary, a high intake of dairy products such as milk increased the risk of developing prostate cancer in Japanese men.

Factors associated with mortality among patients with necrotizing soft tissue infections: An analysis of 4597 cases using the Diagnosis Procedure Combination Database.

OBJECTIVE: This study aimed to determine the factors associated with mortality among patients with necrotizing soft tissue infection (NSTI) in Japan using inpatient data from the Diagnosis Procedure Combination (DPC) Database. METHODS: We conducted a cross-sectional study using a population retrieved from the Japanese DPC inpatient database of patients who underwent surgical operations from 2014 through 2017. The associations between the covariates and mortality were estimated using multivariate logistic regression models. RESULTS: In total, 4597 patients were registered in this study, with an overall mortality rate of 6.9%. Multilevel logistic regression analysis revealed that higher age, lower body mass index (BMI < 18.5 kg/m2), pre-existing cancer diagnosis, sepsis at admission, maintenance dialysis, antithrombin III use, and anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotic use were associated with a high mortality rate among NSTI patients. However, sex, underlying diabetes mellitus, ambulance use at admission, intravenous immunoglobulin use, higher hospital case volume, and frequency of operations were not associated with mortality. CONCLUSION: This study is the first to report the association of lower BMI, antithrombin III use, and anti-MRSA antibiotic use with a higher mortality rate among NSTI patients.

Premature mortality due to stomach cancer in Japan: a nationwide analysis from 1980 to 2015.

PURPOSE: Premature mortality offers an alternative approach for monitoring the burden of mortality; however, little is known about its measures for stomach cancer. In the present study, we investigated temporal changes in premature mortality because of stomach cancer in the Japanese population from 1980 to 2015. METHODS: Mortality data for stomach cancer were obtained from the World Health Organization mortality database. Years of life lost (YLL) was calculated using Japanese life tables. The average lifespan shortened was calculated and defined as the ratio of YLL in relation to the expected lifespan. RESULTS: Over a 35-year time frame, the age-standardized rates adjusted to the World Standard Population for deaths from stomach cancer substantially decreased in both sexes. The results from the average YLL (AYLL) measure showed that lifespan of stomach cancer patients was prolonged by about 3 and 5 years in men and women, respectively. The average lifespan shortened measure showed that stomach cancer led to a loss of 18.5% of lifespan among men and of 21.9% among women in 1980, but these numbers were reduced to 13.6% and 14.5%, respectively, in 2015. CONCLUSIONS: Our study demonstrated decreasing trends in premature mortality for stomach cancer in Japan over a 35-year period.

Relationship between the depressive state of emergency life-saving technicians and near-misses.

AIM: A depressive state is a key risk factor for medical errors made by emergency life-saving technicians (ELSTs). However, no study has examined the occurrence of near-misses in ELSTs. We investigated the association between a depressive state and near-misses among ELSTs. METHODS: A cross-sectional study was undertaken in 345 ELSTs using an anonymous self-administered questionnaire. The main exposure was a depressive state that was measured using the Quick Inventory of Depressive Symptomatology. For the main outcome, near-miss events, we calculated odds ratios (OR) of depressive states, adjusted for age and work-related factors by multivariable logistic regression. For exploratory purposes, we also undertook secondary analyses to determine whether work-related factors were associated with a depressive state. RESULTS: We obtained 254 responses. Compared to ELSTs without a depressive state, the adjusted OR for near-misses among ELSTs with a mild depressive state was 3.14 (95% confidence interval [CI], 1.37-7.16; P = 0.007), and that among ELSTs with a moderate or greater depressive state was 5.29 (95% CI, 1.46-19.09; P = 0.011). For a depressive state, in the exploratory analyses, the OR of nap duration while on duty for less than 2 h was 3.34 (95% CI, 1.15-9.67; P = 0.027), that for irregular mealtime while on duty was 3.71 (95% CI, 2.00-6.86; P < 0.001), and that for a duration of desk work of 4 h or longer was 2.21 (95% CI, 1.15-4.25; P = 0.017). CONCLUSION: A depressive state was significantly associated with the occurrence of near-misses among ELSTs. That a depressive state among ELSTs was related to nap duration and excessive office work indicates that improved management of the work environment and operations of ELSTs is necessary for the provision of safe emergency medical services.

Effectiveness of regional clinical pathways on postoperative length of stay for hip fracture patients: A retrospective observational study using the Japanese Diagnosis Procedure Combination database.

BACKGROUND: Regional clinical pathways, a new type of clinical pathway, are practiced with the aim of standardizing and optimizing medical care by cooperation among multiple medical institutions in a region. However, current evaluation of the effectiveness of regional clinical pathways for hip fracture, a major health problem requiring hospitalization for orthopedic surgery, is insufficient. This study aimed to determine the association between regional clinical pathways and postoperative hospital length of stay (LOS) among hip fracture patients. In particular, we focused on the variation in postoperative LOS of hip fracture patients among hospitals and the contribution of regional clinical pathways to this variation. METHODS: Using data from the Diagnosis Procedure Combination (DPC) database in Japan from April 2011 to March 2013, patients who were diagnosed with "fracture of head and neck of femur" (ICD10 code S72.0) or "pertrochanteric fracture" (S72.1) and received "bipolar hip arthroplasty" or "open reduction and internal fixation" were extracted. A total of 110,133 patients were included. Associations between regional clinical pathways and postoperative LOS were analyzed using cross-sectional analysis with multilevel regression models. RESULTS: Hospitals that implemented a regional clinical pathway showed a significant reduction (13 days) in the postoperative LOS of hip fracture patients. We found a 16% inter-hospital variation in postoperative LOS, which might be explained by hospital-level implementation of regional clinical pathways. Application of regional clinical pathways at the patient level resulted in a 4-day decrease in postoperative LOS. CONCLUSIONS: Implementation of regional clinical pathways for hip fracture patients at the hospital level was associated with reduced postoperative LOS, regardless of whether or not pathways were implemented at the patient level. This suggests that regional clinical pathways are effective for patient care management in hospitals.

Laparoscopic uterosacral ligament colpopexy for apical support in addition to hysterectomy for pelvic organ prolapse.

AIM: To evaluate the perioperative complications and the anatomical outcomes of our laparoscopic uterosacral ligament (USL) colpopexy, which is a novel laparoscopic technique for the management of uterine prolapse. The objective was to report on outcome after 2 years of a technique using laparoscopic USL colpopexy. METHODS: A total of 152 uterine prolapse patients underwent laparoscopic USL colpopexy from May 2013 to April 2015. We described the surgical technique and performed a retrospective analysis of this laparoscopic technique. Patients underwent standardized assessment and examination using pelvic organ prolapse quantification (POP-Q) score. The dependent values of Ba point (bladder), C point (vaginal cuff) and Bp point (rectum) were recorded preoperatively, and at 1, 3, 6, 12 and 24 months of postoperative examination. Pre/postoperative data were compared using the Kaplan-Meier method. RESULTS: Mean age, operative time and amount of hemorrhage were 68.2 ± 7.5 years, 118.3 ± 36.4 min and 60.5 ± 73.3 mL, respectively. Overall recurrent prolapse, which was defined as POP-Q stage II or higher, was noted in 29 patients (19%). However, only 2 patients presented recurrent rectocele among 51 patients with preoperative POP-Q stage II of uterine prolapse alone (recurrence rate; 3.9%). The pre/postoperative average POP-Q scores were -0.2/-2.7 cm (P < 0.05) at Ba point, -1.9/-5.1 cm (P < 0.05) at C point and -2.4/-2.3 cm (P = 0.06) at Bp point. CONCLUSION: Laparoscopic visualization of uterosacral ligaments may result in safe colpopexy. Our results show this will be a useful procedure for apical support as native tissue repair.

The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 in a pooled analysis of 16,024 men from 22 studies.

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

Equality of Treatment for Hip Fracture Irrespective of Regional Differences in Socioeconomic Status: Analysis of Nationwide Hospital Claims Data in Japan.

Despite the wide variety of international evidence on the relationship between the socioeconomic status (SES) and health outcomes, less is known about the association between SES and healthcare provider practices. We assessed whether patients with a closed hip fracture were treated differently by hospital physicians according to the SES of their residential areas in Japan. Hip fracture is a common cause of hospitalization among the elderly, but the relationship between SES and hip fracture treatment remains unknown in Japan. We employed the Diagnosis Procedure Combination (DPC) database from April 2011 to March 2014. SES of the patient's residential area was estimated using Census-derived areal deprivation index (ADI). We performed a cross-sectional study of national claims data and analyzed it using cross-classified multilevel models. We used two outcome measures: (i) whether the patient received an operation or was treated by watchful waiting; and (ii) number of waiting days until operation following admission. We identified 95,011 patients admitted to 1,050 hospitals. Of these, 85,480 patients underwent surgery. Low SES of residential areas was not correlated with the chance of undergoing surgery (P = 0.15) but was weakly correlated with longer waiting days (coefficient, 0.03; 95% confidence interval, -0.01 to 0.06; P = 0.08). The difference of waiting days between maximum (10.4) and minimum ADI (-4.0) was marginal (0.39 days). The results indicate the SES of patient's residential area does not affect the decision of surgical treatment for hip fracture and has ignorable impact on waiting days from hospital admission to surgery.

Premature Mortality Due to Malignancies of the Kidney and Bladder in Japan, 1980-2010.

BACKGROUND: In the present study, we examined the trends of premature mortality due to kidney and bladder cancers among the Japanese population from 1980 through 2010. METHODS: Mortality data were obtained from the World Health Organization mortality database. Years of life lost (YLL) was estimated using Japanese life tables. Average lifespan shortened (ALSS) was calculated and defined as the ratio of years of life lost relative to the expected lifespan. RESULTS: Over the study period, the age-standardized rates to the World Standard Population for deaths from kidney and bladder cancers were stable. The average years of life lost (AYLL) measure shows decreases of about 4 and 6 years of life for kidney cancer in men and women, respectively, and decreases of about 2 years of life for bladder cancer in both sexes. The ALSS shows that patients with kidney cancer lost 21.0% and 24.7% of their lifespan among men and women in 1980, whereas respective losses were 15.3% and 15.8% in 2010. Also, patients with bladder cancer on average lost 13.5% in men and 14.2% in women in 1980 and 10.8% in men and 11.1% in women in 2010. CONCLUSIONS: Our study shows favorable trends in premature mortality for kidney and bladder cancers in Japan over a 30-year period; however, patients with bladder cancer on average lost a smaller proportion of their lifespan compared to those with kidney cancer. The development of a novel ALSS measure is convenient in examination of the burden of premature mortality over time.

Clinical Significance of Squamous Differentiation in Urothelial Carcinoma of the Bladder.

The prognostic value of squamous differentiation (SD) in urothelial carcinoma (UC) of the bladder is unclear. The aim of this study was to identify the clinical significance of SD in UC in terms of oncological outcomes in patients undergoing radical cystectomy (RC). We evaluated consecutive patients with muscle-invasive bladder cancer (MIBC; clinical T2-4aN0M0) treated with RC at our institution from March 2003 to March 2017. We enrolled 20 and 81 patients with UC with SD (UCSD) and pure UC, respectively. Postoperative survival outcomes were compared between the patients with UCSD and pure UC using the Kaplan-Meier method. Pre- and postcystectomy factors that influenced the overall survival (OS) and recurrence-free survival (RFS) were investigated in these patients. Multivariate Cox regression models were used to identify the predictors of OS and RFS. With a median follow-up time of 31 months, the 5-year OS rate of the UCSD and pure UC groups was 41.1% and 69.7% ( P = .002) and the 5-year RFS rate was 51.8% and 59.5% ( P = .027), respectively. The shape of the Kaplan-Meier curves for UCSD suggested a more rapid course of the disease within the first 2 years than observed in pure UC. Multivariate analyses suggested that SD in UC was significantly associated with OS (hazard ratio [HR]: 4.22; 95% confidence interval [CI]: 1.20-14.8; P = .024) and close to significance for a lower RFS (HR: 2.13, 95% CI: 0.74-6.15, P = .064). Our results indicate that SD may be an independent predictor of OS and RFS in UC of MIBC in patients undergoing RC.

Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies.

BACKGROUND: Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting. OBJECTIVE: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration. RESULTS AND LIMITATIONS: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p<0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (phet=0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation. CONCLUSIONS: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade. PATIENT SUMMARY: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.

Circulating isoflavone and lignan concentrations and prostate cancer risk: a meta-analysis of individual participant data from seven prospective studies including 2,828 cases and 5,593 controls.

Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between prediagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs. Q1 = 0.61, 95% confidence interval [CI] = 0.39-0.97), although there was no significant trend (OR per 75 percentile increase = 0.69, 95 CI = 0.46-1.05, ptrend = 0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs. Q1 = 0.70, 0.45-1.10 and 0.71, 0.45-1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that prediagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.