Prevalence and impact on daily life of lower urinary tract symptoms in Japan: Results of the 2023 Japan Community Health Survey (JaCS 2023).

OBJECTIVES: A large-scale nationwide epidemiological survey of lower urinary tract symptoms (LUTS) was conducted via the Internet in 2023 to clarify the current prevalence of LUTS and evaluate its impact on daily life in Japan. METHODS: The survey was conducted among individuals aged 20-99 years old who had anonymously registered with a Japanese online research company. The survey consisted of 48 questions related to LUTS and daily life. RESULTS: A total of 6210 participants (3088 females and 3122 males), who were selected by probability sampling based on the composition of the Japanese population (age range: 20-99), were recruited. The overall prevalence of LUTS was 77.9% among the subjects aged ≥20 and 82.5% among those aged ≥40. The prevalence of LUTS differed between the sexes and trends toward significant increases in prevalence with age were seen for almost all LUTS. Furthermore, the prevalence of overactive bladder (OAB) was 11.9% among the subjects aged ≥20 and 13.8% among those aged ≥40. This study also showed that LUTS negatively affected daily life. However, the percentage of subjects who visited a physician to receive treatment for LUTS was low, including for participants with a history of treatment for LUTS, although this increased with age. CONCLUSION: The prevalence of LUTS, including OAB, increased with age and negatively affected daily life. However, since the percentage of patients who visit a physician to receive treatment for LUTS remains low, further educational activities regarding LUTS are necessary.

Photodynamic diagnosis-assisted transurethral resection of bladder tumor for high-risk non-muscle invasive bladder cancer improves intravesical recurrence-free survival (BRIGHT study).

OBJECTIVES: In a primary analysis of data from the BRIGHT study (UMIN000035712), photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) using oral 5-aminolevulinic acid hydrochloride reduced residual tumors in high-risk non-muscle invasive bladder cancer (NMIBC). We aimed to evaluate the effectiveness of PDD-TURBT for intravesical recurrence after a second transurethral resection for high-risk NMIBC. METHODS: High-risk NMIBC patients initially treated with PDD-TURBT (PDD group) were prospectively registered between 2018 and 2020. High-risk patients with NMIBC who were initially treated with white-light TURBT (WL group) were retrospectively registered. Intravesical recurrence-free survival after the second transurethral resection was compared between the PDD and WL groups using propensity score matching analysis. RESULTS: In total, 177 patients were enrolled in the PDD group, and 306 patients were registered in the WL group. After propensity score matching (146 cases in each group), intravesical recurrence within 1 year was significantly less frequent in the PDD group than in the WL group (p = 0.004; hazard ratio [HR] 0.44, 95% confidence interval [CI]: 0.25-0.77). In subgroup analysis, PDD-TURBT showed a particularly high efficacy in reducing intravesical recurrence within 1 year, especially in cases of tumors measuring less than 3 cm (p = 0.003; HR 0.31, 95% CI: 0.14-0.67), absence of residual tumor at second transurethral resection (p = 0.020; HR 0.37, 95% CI: 0.16-0.86), and no postoperative intravesical Bacillus Calmette-Guérin therapy (p < 0.001; HR 0.27, 95% CI: 0.13-0.58). CONCLUSIONS: PDD-TURBT may reduce short-term intravesical recurrence in patients with high-risk NMIBC.

Heterogeneity of Hippo signalling activity in different histopathologic subtypes of renal cell carcinoma.

This study aimed to reveal the prognostic role of the Hippo pathway in different histopathological subtypes of renal cell carcinoma (RCC). The TCGA-KIRC (n = 537), TCGA-KIRP (n = 291) and TCGA-KICH (n = 113), which contain data about clear cell (ccRCC), papillary (pRCC) and chromophobe RCC (chRCC), respectively, were investigated. Gene Set Variation Analysis was used to compare the activity of many pathways within a single sample. Oncogenic pathway-related expression differed between cases of ccRCC involving low and high Hippo pathway activity. There were two subsets of ccRCC, in which the cancer exhibited lower and higher Hippo signalling activity, respectively, compared with normal tissue. In the ccRCC cohort, lower Hippo pathway activity was associated with a higher clinical stage (p < 0.001). The Hippo pathway (HR = 0.29; 95% CI = 0.17-0.50, p < 0.001), apoptosis (HR = 6.02; 95% CI = 1.47-24.61; p = 0.013) and the p53 pathway (HR = 0.09; 95% CI = 0.02-0.36; p < 0.001) were identified as independent prognostic factors for ccRCC. The 5-year overall survival of the ccRCC patients with low and high Hippo pathway activity were 51.9% (95% CI = 45.0-59.9) and 73.6% (95% CI = 67.8-79.9), respectively. In conclusion, the Hippo pathway plays an important role in the progression of ccRCC. Low Hippo pathway activity is associated with poor outcomes in ccRCC, indicating the tumour suppressor function of this pathway.

Mirabegron for overactive bladder in frail patients 80 years or over (HOKUTO study).

BACKGROUND: We assessed the efficacy and safety of mirabegron, a ß3-adrenoceptor agonist, in older adults (≥ 80 years old) with overactive bladder (OAB). METHODS: OAB patients aged ≥ 80 years were enrolled in this prospective, single-arm observational study. OAB was diagnosed based on the OAB symptom score (OABSS); i.e., a total score of ≥ 3 points and an urgency score of ≥ 2 points. Patients who received 50 mg mirabegron once daily were evaluated at the baseline and at 4, 8, and 12 weeks. The changes from the baseline in the OABSS, International Prostate Symptom Score (IPSS), OAB questionnaire (OAB-q) score, and Vulnerable Elders Survey (VES-13) score were determined. Adverse events, laboratory tests, 12-lead electrocardiography, the QT interval according to Fridericia's formula (QTcF), uroflowmetry, the post-void residual urine volume (PVR), and the Mini-Mental State Examination (MMSE) score were used to assess safety. RESULTS: Forty-three patients (median age: 84 years, range: 80-96 years) were examined. They had high rates of comorbidities and polypharmacy. Mirabegron significantly improved in total score of the OABSS, including urgency and urge incontinence. The total IPSS, IPSS quality-of-life (QOL) index, and OAB-q scores also significantly improved. Mirabegron improved in the VES-13 score. There were no significant changes in laboratory test values, uroflowmetry findings, PVR, the QTcF, or MMSE score. Two patients (4.7%) withdrew from the study after experiencing adverse events. CONCLUSIONS: Mirabegron was well tolerated and significantly improved in OAB symptoms, and QOL in older patients. Trial registration The present clinical study was approved by University of Yamanashi Institutional Review Board prior to study initiation (ID1447) and was retrospectively registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (UMIN000045996) on Nov 6, 2021.

Potential Targets for Overactive Bladder in Older Men Based on Urinary Analysis of Metabolomics.

OBJECTIVE: We investigated the association between overactive bladder (OAB) and urinary metabolites in men. METHODS: This prospective observational study included 42 men aged 65-80 years. The 3-day frequency volume chart (FVC), International Prostate Symptom Score (IPSS), and quality of life score were adapted to assess the micturition behavior. Participants with IPSS urgency score ≥2 were included in the OAB group, and those with IPSS urgency score <2 were included in the control group. We performed a comprehensive metabolomic analysis using urine samples. Metabolites were compared between the groups using an unpaired t test and Fisher's exact test in a nonadjusted analysis. Multivariable logistic regression analysis was performed to investigate the association between OAB and the metabolites. RESULTS: Overall, 23 men were included in the OAB group and 19 in the control group. There were no differences in the background factors except age between the groups. FVC analysis demonstrated that nocturnal urine volume, 24-h micturition frequency, and nocturnal micturition frequency were significantly higher, and the maximum voided volume was significantly lower in the OAB group than in the controls. Metabolomic analysis revealed 14 metabolites that were differentially expressed between the groups. Multivariate analysis indicated that an increase in the levels of 5-iso prostaglandin F2α-VI (5-iPF2a-VI) and 5-methoxyindoleacetic acid was associated with OAB. CONCLUSION: Abnormal urinary metabolites, including metabolites in the tryptophan (5-methoxyindoleacetic acid, 3-indoleacetonitrile, and 3-hydroxyanthranilic acid) and arachidonic acid (5-iPF2a-VI) pathways, play a role in the pathogenesis of OAB in older men.

Outcomes of artificial urinary sphincter implantation in patients with diabetes mellitus: A subgroup analysis.

OBJECTIVES: To estimate the surgical and quality-of-life outcomes of artificial urinary sphincter implantation in patients with diabetes mellitus (DM). Subanalyses were performed using the same population as that in our previous multicenter, prospective, observational study. METHODS: A total of 135 male patients who underwent primary artificial urinary sphincter implantation were divided into two groups: those with and without DM. The revision-free rates, that is, the percentage of patients who did not require revision surgery, were compared between patients with and without DM. The number of urinary pads required per day, International Consultation on Incontinence Questionnaire-Short Form, and King's Health Questionnaire were used to compare the continence status and quality of life (QOL) between the two groups preoperatively and at 1, 3, and 12 months after surgery. RESULTS: Revision-free rates were significantly lower in the DM group (83.9%, 77.4%, and 67.8% at 1, 2, and 3 years after implantation, respectively) than in the non-DM group (95.5%, 92.5%, and 85.5% at 1, 2, and 3 years after implantation, respectively). Both continence status and QOL, assessed by questionnaires, markedly improved after surgery in patients with and without DM. CONCLUSIONS: Despite differences in the durability of the artificial urinary sphincters, patients with DM can obtain as much benefit from artificial urinary sphincter implantation regarding continence and quality-of-life improvement as patients without DM. Therefore, DM was not considered a comorbidity that contraindicated artificial urinary sphincter implantation. Additional large-scale studies are required to verify our findings.

Bladder cancer prospective cohort study on high-risk non-muscle invasive bladder cancer after photodynamic diagnosis-assisted transurethral resection of the bladder tumor (BRIGHT study).

OBJECTIVES: Transurethral resection of bladder tumor with photodynamic diagnosis has been reported to result in lower residual tumor and intravesical recurrence rates in non-muscle invasive bladder cancer. We aimed to evaluate the usefulness of photodynamic diagnosis-transurethral resection of bladder tumor combined with oral 5-aminolevulinic acid hydrochloride for high-risk non-muscle invasive bladder cancer. METHODS: High-risk non-muscle invasive bladder cancer patients with an initial photodynamic diagnosis-transurethral resection of bladder tumor (photodynamic diagnosis group) were prospectively registered between 2018 to 2020. High-risk non-muscle invasive bladder cancer cases with a history of initial white-light transurethral resection of bladder tumor (white-light group) were retrospectively registered. Propensity score-matching analysis was used to compare residual tumor rates, and factors that could predict residual tumors at the first transurethral resection of bladder tumor were evaluated. RESULTS: Analyses were conducted with 177 and 306 cases in the photodynamic diagnosis and white-light groups, respectively. The residual tumor rates in the photodynamic diagnosis and white-light groups were 25.7% and 47.3%, respectively. Factor analysis for predicting residual tumors in the photodynamic diagnosis group showed that the residual tumor rate was significantly higher in cases with a current/past smoking history, multiple tumors, and pT1/pTis. When each factor was set as a risk level of 1, cases with a total risk score ≤1 showed a significantly lower residual tumor rate than cases with a total risk score ≥2 (8.3% vs 33.3%, odds ratio 5.46 [1.81-22.28]). CONCLUSIONS: In high-risk non-muscle invasive bladder cancer cases, the odds of a residual tumor after initial photodynamic diagnosis-transurethral resection of bladder tumor were 0.39-fold that of the odds of those after initial white-light transurethral resection of bladder tumor. A risk stratification model could be used to omit the second transurethral resection of bladder tumor in 27% of the cases.

Cine magnetic resonance imaging provides novel predictors of early continence recovery after radical prostatectomy: Assessment of the dynamics of pelvic floor muscles.

AIMS: Postprostatectomy incontinence is a major complication of prostatectomy. Although pelvic floor muscle training can successfully treat postprostatectomy incontinence, evidence for how muscle movement affects continence recovery is lacking. We evaluated dynamic factors of prostatectomy patients using cine magnetic resonance imaging to identify risk factors for postprostatectomy incontinence and reveal the contribution of pelvic floor muscles to continence recovery. METHODS: A total of 128 prostate cancer patients who underwent robot-assisted laparoscopic surgery were enrolled. Cine magnetic resonance imaging was performed preoperatively and 6 months after surgery. Continence was defined as pad-free or use of safety pads. We defined the bladder neck elevation distance during pelvic floor muscle training as the bladder elevation distance. Patients with continence recovery within 1 month comprised the continence group (n = 48); other patients comprised the incontinence group (n = 80). RESULTS: The preoperative bladder elevation distance was significantly longer in the continence group than in the incontinence group (10.4 vs. 8.2 mm; p < .001). The postoperative bladder elevation distance of the continence group tended to be longer (9.9 vs. 8.9 mm; p = .057). Multivariate analysis showed that the preoperative bladder elevation distance significantly contributed to continence recovery (p = .016). Patients with a longer preoperative bladder elevation distance (>8.5 mm) experienced continence recovery significantly faster than patients with a shorter distance (<8.5mm) (p = .038). CONCLUSIONS: Bladder elevation distance, a novel dynamic parameter, was strongly associated with early continence recovery. Cine magnetic resonance imaging can assess a patient's risk of postprostatectomy incontinence and guide pelvic floor muscle training.

Hypoxia-induced thyroid hormone receptor expression regulates cell-cycle progression in renal tubule epithelial cells.

Hypoxia occurs in the kidneys of chronic kidney disease (CKD) patients, inducing interstitial fibrosis and tubule cell death. Renal tubule cell death is an important determinant of mortality in CKD. We focused on the regulation of cell-cycle-mediated protein expression to prevent cell death under chronic hypoxia in the kidneys of CKD patients. Paraffin-embedded kidney sections from patients with CKD (diabetes nephropathy, nephrosclerosis, or IgA nephropathy) were analyzed for the expression of hypoxia-inducible factor (HIF), thyroid hormone receptor (TR) ß, or p21 and levels of interstitial fibrosis. Human renal proximal tubule cells were exposed to hypoxia and analyzed for the expression of HIF, TRß, or p21 and the cell-cycle stage. TRß expression was enhanced early on when fibrosis was not fully developed in the tubule cells of CKD patients. HIF1α bound to the TRß promoter and directly induced its transcription. Further, HIF1α expression induced the expression of TRß and inhibited cell-cycle progression. In the early stage of kidney injury, TRß might act as a guardian to prepare and organize cell-cycle proliferation and prevent cell death. While the molecular mechanism that regulates the expression of cell-cycle regulators in renal tubule cells remains controversial, TRß has strong potential as a new therapeutic target.

Effects of the prenatal environment on cryptorchidism: A narrative review.

Cryptorchidism, the absence of testes from the scrotum, is the most common genital disorder in boys and a risk factor for reduced fertility and testicular cancer. The mechanism responsible for cryptorchidism involves two discrete stages: a transabdominal and an inguinoscrotal phase. These phases of testicular descent are regulated by the prenatal sex hormone environment, including levels of testosterone, insulin-like factor 3, and calcitonin gene-related peptide. Environmental endocrine disruptors, which are unfavorable environmental factors, may also affect testicular descent through prenatal sex hormones. This review examined the effects of environmental factors, particularly environmental endocrine disruptors, such as phthalates, organochlorine pesticides, diethylstilbestrol, bisphenol A, dioxins/dioxin-like compounds, and perfluoroalkyl substances, and parental lifestyles on the risk of cryptorchidism. Although some studies have shown that environmental endocrine disruptors can affect testicular descent by changing the hormonal environment during the prenatal period, no significant association has been established between exposure to environmental endocrine disruptors and the incidence of cryptorchidism. Therefore, the role played by environmental endocrine disruptor exposure (if any) in the pathogenesis of cryptorchidism remains unknown. Further studies are needed to examine these issues.