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.

Clinicopathological characteristics of adrenocortical carcinoma in the Kyushu-Okinawa area of Japan.

OBJECTIVE: Adrenocortical carcinoma is a rare condition, with limited comprehensive reports from Japan. This study aimed to review Japan's data on adrenocortical carcinoma by assessing information from 46 patients-with adrenocortical carcinoma across 10 Japanese university hospitals. METHODS: We conducted a retrospective multi-institutional analysis of the clinical characteristics of adrenocortical carcinoma in Japan. We evaluated data from 46 patients across 10 university hospitals over 10 years and analyzed the relationship between clinicopathological characteristics and overall survival. RESULTS: Five- and 10-year overall survival rates were 59% and 53%, respectively. Overall survival was significantly different among the tumor-node-metastasis system for adrenocortical carcinoma of the American Joint Committee on Cancer/International Union Against Cancer, with the worst prognosis in stage IV (p = 0.0044). In our cohort, neither the Weiss score nor the Ki-67 proliferation index correlated with overall survival. Adjuvant treatment did not yield improved overall survival, whereas resection of the primary tumor in stage IV disease was significantly associated with improved overall survival (p = 0.0262). Out of the cases evaluated for plasma hormones, plasma cortisol, aldosterone, testosterone, and DHEA-S levels were measured at 23%, 42%, 29%, and 62%, respectively, demonstrating higher levels than the upper normal limits. CONCLUSION: Patients with stage IV adrenocortical carcinoma had a poor prognosis; however, resection of the primary tumor in stage IV disease was associated with prolonged survival. The results of this study are expected to contribute to future treatment of adrenocortical carcinoma in Japan.

Factors Related to Overactive Bladder-like Symptoms in Bladder Cancer.

BACKGROUND/AIM: The aim of the present study was to investigate the factors related to overactive bladder (OAB)-like symptoms in patients with bladder cancer. PATIENTS AND METHODS: This study included 59 patients who underwent transurethral resection of bladder tumor (TURBT). OAB-like symptoms were identified based on the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score (IPSS) questionnaires. The main outcome measures were elucidation of bladder cancer-related factors that might induce OAB-like symptoms. RESULTS: Non-muscle invasive bladder cancer (NMIBC) was observed in 50 patients, and carcinoma in situ (CIS) was observed in 14 patients. OABSS total score, IPSS total score, and quality of life index were 5±3, 12±7 and 3±1, respectively. The OABSS question 1 score, indicating pollakisuria, was significantly higher in NMIBC patients with CIS than in those without CIS (presence of CIS vs. absence of CIS=1.0±0.6 : 0.5±0.6, p=0.02). IPSS question 4 score, indicating urgency (r=0.31, p=0.01), and OABSS question 4 score, indicating urgency incontinence (r=0.29, p=0.03), correlated significantly with the maximum bladder tumor diameter. Multivariate regression analysis demonstrated that presence of CIS in NMIBC cases correlated significantly with pollakisuria (p=0.02), and that maximum diameter of the bladder tumor correlated significantly with both urgency (p=0.04) and urgency incontinence (p=0.01). CONCLUSION: CIS induced pollakisuria in NMIBC. Larger diameter bladder tumors induced both urgency and urgency incontinence. Patients with bladder cancer who present with pollakisuria might have CIS.

Real-world treatment outcomes of patients with penile cancer in the Kyushu-Okinawa area of Japan in the pre-guideline era.

OBJECTIVES: To understand the real-world outcomes for patients with penile cancer in the Kyushu-Okinawa area before the introduction of practice guidelines in Japan. METHODS: We retrospectively collected medical information on patients with penile squamous cell carcinoma and penile intraepithelial neoplasia at 12 university hospitals and their affiliated hospitals in the Kyushu-Okinawa area from January 2009 to December 2020. Patients with unknown clinical stage were excluded. Patient background characteristics and survival, as well as pretreatment factors involved in survival, were investigated. RESULTS: A total of 196 patients were included. Patients with clinical stage 0, I, IIA, IIB, IIIA, IIIB and IV comprised 9.7, 26.0, 22.4, 2.6, 10.7, 14.3 and 14.3%, respectively. The median follow-up was 26 months, and the mean 5-year overall survival and cancer-specific survival rates were 74.3 and 79.8%, respectively. On univariate analysis, tumor diameter ≥ 30 mm, penile shaft tumor, Eastern Cooperative Oncology Group performance status ≥ 1, cT ≥ 3, cN ≥ 2 and cM1 were associated with significantly poorer cancer-specific survival. On multivariate analysis, pretreatment factors of cN ≥ 2 (hazard ratio, 32.5; 95% confidence interval, 5.08-208; P = 0.0002), Eastern Cooperative Oncology Group performance status ≥ 1 (4.42; 1.79-10.9; P = 0.0012) and cT ≥ 3 (3.34; 1.11-10.1; P = 0.0319) were identified as independent prognostic factors. CONCLUSIONS: The study revealed basic data for future penile cancer treatment and research, including survival rates according to clinical stages, and identified cN ≥ 2, Eastern Cooperative Oncology Group performance status ≥ 1 and cT ≥ 3 at initial diagnosis as independent prognostic factors. Evidence for penile cancer in Japan is particularly scarce, and future large-scale prospective studies are warranted.

Differentiation of human adipose tissue-derived mesenchymal stromal cells into steroidogenic cells by adenovirus-mediated overexpression of NR5A1 and implantation into adrenal insufficient mice.

BACKGROUND AIMS: Cell therapy for adrenal insufficiency is a potential method for physiological glucocorticoid and mineralocorticoid replacement. We have previously shown that mouse mesenchymal stromal cells (MSCs) differentiated into steroidogenic cells by the viral vector-mediated overexpression of nuclear receptor subfamily 5 group A member 1 (NR5A1), an essential regulator of steroidogenesis, and their implantation extended the survival of bilateral adrenalectomized (bADX) mice. METHODS: In this study, we examined the capability of NR5A1-induced steroidogenic cells prepared from human adipose tissue-derived MSCs (MSC [AT]) and the therapeutic effect of the implantation of human NR5A1-induced steroidogenic cells into immunodeficient bADX mice. RESULTS: Human NR5A1-induced steroidogenic cells secreted adrenal and gonadal steroids and exhibited responsiveness to adrenocorticotropic hormone and angiotensin II in vitro. In vivo, the survival time of bADX mice implanted with NR5A1-induced steroidogenic cells was significantly prolonged compared with that of bADX mice implanted with control MSC (AT). Serum cortisol levels, which indicate hormone secretion from the graft, were detected in bADX mice implanted with steroidogenic cells. CONCLUSIONS: This is the first report to demonstrate steroid replacement by the implantation of steroid-producing cells derived from human MSC (AT). These results indicate the potential of human MSC (AT) to be a source of steroid hormone-producing cells.

Efficacy and Safety of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Therapy for Anemia in Renal Transplantation Patients by Prior Erythropoiesis Stimulating Agent Use.

BACKGROUND: The present study aimed to clarify the efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) therapy for anemia in renal transplant (RTx) patients. METHODS: After successful RTx, 26 patients requiring treatment for anemia were divided into 2 groups (erythropoiesis-stimulating agent [ESA] group and non-ESA group) based on whether an ESA was used before starting HIF-PHI therapy. The chronological changes in hemoglobin (Hb) values during the 6 months after the start of HIF-PHI therapy were investigated in each group, and the incidence of adverse events was compared. RESULTS: There were 18 patients in the ESA group and 8 patients in the non-ESA group. The median (IQR) Hb values in the 2 groups were 11.35 (10.4-12.3) and 10.15 (8.9-10.4) g/dL, respectively. The chronological changes in the median (IQR) Hb values pre-HIF-PHI and 1, 3, and 6 months after starting HIF-PHI were 11.4 (10.4-12.4), 12.0 (10.7-12.4), 11.9 (10.9-13.4), and 11.5 (10.6-12.7) g/dL, respectively, in the ESA group, and 10.2 (8.7-10.4), 11.0 (10.4-11.7), 12.2 (11.6-13.2), and 12.5 (11.3-12.7) g/dL, respectively, in the non-ESA group. In the ESA group, Hb values were not significantly decreased after HIF-PHI administration (P = .14); in the non-ESA group, Hb values improved significantly (P = .002). Two patients developed diarrhea in the ESA group, and one patient developed appetite loss in the non-ESA group. CONCLUSIONS: Hypoxia-inducible factor prolyl hydroxylase inhibitor was effective and safe for RTx patients regardless of prior ESA use.

Antibody acquisition after second and third SARS-CoV-2 vaccinations in Japanese kidney transplant patients: a prospective study.

BACKGROUND: Kidney transplant patients have lower antibody acquisition after SARS-CoV-2 vaccination. The efficacy of vaccines in Japanese kidney transplant patients with specific characteristics, such as predominant living-donor, ABO-incompatible kidney transplant, and low-dose immunosuppression, requires verification. METHODS: We conducted a prospective study to estimate anti-SARS-CoV-2 antibody levels in 105 kidney transplant patients and 57 controls. Blood samples were obtained before vaccination, 1, 3, and 6 months after second vaccination, and 1 month after third vaccination. We investigated antibody acquisition rates, antibody levels, and factors associated with antibody acquisition. RESULTS: One month after second vaccination, antibody acquisition was 100% in the controls but only 36.7% in the kidney transplant group (P < 0.001). Antibody levels in positive kidney transplant patients were also lower than in the controls (median, 4.9 arbitrary units vs 106.4 arbitrary units, respectively, P < 0.001). Years after kidney transplant (odds ratio 1.107, 95% confidence interval 1.012-1.211), ABO-incompatible kidney transplant (odds ratio 0.316, 95% confidence interval 0.101-0.991) and mycophenolate mofetil use (odds ratio 0.177, 95% confidence interval 0.054-0.570) were significant predictors for antibody acquisition after second vaccination. After third vaccination, antibody positivity in the kidney transplant group increased to 75.3%, and antibody levels in positive patients were 71.7 arbitrary units. No factors were associated with de novo antibody acquisition. CONCLUSIONS: In Japanese kidney transplant patients, years after kidney transplant, ABO-incompatible kidney transplant and mycophenolate mofetil use were predictors for antibody acquisition after second vaccination. Third vaccination improves antibody status even in patients who were seronegative after the second vaccination.

Effect of Pharmacotherapy for Overactive Bladder on the Incidence of and Factors Related to Urinary Tract Infection: A Systematic Review and Meta-analysis.

PURPOSE: The aim of this meta-analysis was to investigate the effect of pharmacotherapy for overactive bladder on the pathogenesis of urinary tract infection. MATERIALS AND METHODS: A comprehensive search was performed in MEDLINE and the Cochrane Library using terms for overactive bladder, antimuscarinic agents, and beta 3-adrenoceptor agonists. The primary end point was the emergence of urinary tract infection after pharmacotherapy for overactive bladder. The secondary end point was the emergence of urinary retention, dysuria, and/or increased residual urine volume after overactive bladder treatment. Meta-analyses were conducted using random-effects models. RESULTS: A total of 35,939 patients in 33 trials (29 trials of antimuscarinic agents vs placebo, and 9 trials of beta 3-adrenoceptor agonists vs placebo) that included patients with overactive bladder were identified. At 1-3 months after treatment, the incidence of urinary tract infections was statistically significantly higher in the patients treated with antimuscarinic agents (RR: 1.23, 95% CI: 1.04, 1.45; P = .013) than in the placebo control group. The incidence of urinary tract infections was not increased in the patients treated with beta 3-adrenoceptor agonists (RR: 1.04, 95% CI: 0.76, 1.42; P = .796). Antimuscarinic agents also statistically significantly increased the risks of urinary retention, dysuria, and/or increased residual urine volume (RR: 2.88, 95% CI: 1.79, 4.63; P < .001), whereas beta 3-adrenoceptor agonists did not (RR: 1.26, 95% CI: 0.38, 4.14; P = .708). CONCLUSIONS: This meta-analysis showed that antimuscarinic agents statistically significantly increased the incidences of urinary tract infection and lower urinary tract symptoms and dysfunction, but beta 3-adrenoceptor agonists did not. To prevent urinary tract infection emergence, beta 3-adrenoceptor agonists might be safer than antimuscarinic agents.

Drugs Showing Real-world Efficacy for Nocturia in Patients With Bladder Storage Symptoms.

BACKGROUND/AIM: Nocturia is defined as the symptom that an individual has to disrupt their sleep at night, for one or several times, in order to void. Nocturia is a bothersome event that markedly reduces a patient's quality of life. The aim of the study was to elucidate which drugs, prescribed to reduce nocturia, show real-world efficacy in patients with bladder storage symptoms. PATIENTS AND METHODS: One hundred consecutive patients who visited the Fukuoka University Medical Center were evaluated between May and July 2022. Anticholinergic drugs, ß3 adrenoceptor agonists, α1 blockers, desmopressin, and other medicines were prescribed for relieving nocturia. Desmopressin was used as second-line treatment of nocturia only in males with nocturnal polyuria. The association between each drug and actual decrease in nocturia was investigated using multivariate analysis. RESULTS: The number of nocturia episodes was reduced in patients using anticholinergic drugs, ß3 adrenoceptor agonists, and desmopressin (-1.4±0.9, -1.3±0.9, -2.0 ±0.8 episodes/night, respectively). Multivariate analysis for the entire cohort showed that anticholinergic drugs and ß3 adrenoceptor agonists were associated with significantly decreased nocturia episodes (p=0.01 and p=0.04, respectively). In males, only desmopressin was associated with a significant decrease in nocturia (p=0.03), and combination therapy significantly decreased the number of nocturia episodes compared to monotherapy (p=0.001). CONCLUSION: In a real-world clinical setting, anticholinergic drugs and ß3 adrenoceptor agonists were similarly effective in reducing nocturia. Administration of desmopressin combined with anticholinergic drugs and/or ß3 adrenoceptor agonists is the most effective method for reducing nocturia in male patients with both storage symptoms and nocturnal polyuria.

Real-World Evidence for Risk Factors of Bruises and Fractures from Falls in Patients with Overactive Bladder: A Medical Record Analysis.

Aim: To identify the risk factors for bruises and fractures from falls in patients with overactive bladder (OAB). Methods: We evaluated 1136 patients with OAB and aged ≥50 years who visited our hospital. Age, sex, frequency of nocturnal urination, and urinary incontinence type were investigated in the 360 eligible patients. Patients were divided into three groups: those patients without falls (no-fall group), those with fall bruises (bruise group), and those with fall fractures (fracture group). The risk factors for bruises and fractures in patients with OAB were evaluated using the logistic regression analysis. In addition, association between the bruises or fractures from falls and the behavior around urination during the night was investigated. Results: The multivariate logistic regression analysis showed that female sex (odds ratio (OR) 2.888, p = 0.030) and nocturnal urination frequency ≥3 times/night (OR vs. ≤2 times/night, 2.940; p = 0.040) were significantly associated with bruises. Nocturnal urination frequency ≥3 times/night (OR vs. ≤2 times/night, 2.835; p = 0.026) and urge incontinence (OR 3.415, p = 0.016) were significantly associated with fractures. Behavior around urination during the night was significantly associated with fractures (p = 0.009). Conclusion: In the real-world clinical setting, increasing nocturnal urination frequency is a common risk factor for bruises and fractures. Also, female sex and urge incontinence were the risk factors for bruises and fractures, respectively. OAB patients with urge incontinence would especially require aggressive intervention to prevent fractures during night-time voiding.

Exacerbation of Urinary Storage Symptoms by the Psychological Stress Induced by the COVID-19 Pandemic.

BACKGROUND/AIM: This study aimed to determine whether psychological stress associated with the COVID-19 pandemic might exacerbate lower urinary tract symptoms (LUTS) and decrease lower urinary tract function in outpatients with LUTS. PATIENTS AND METHODS: We evaluated 104 patients who visited our hospital during the first wave of the COVID-19 pandemic. Psychological stress was evaluated by the Stress Response Scale-18 (SRS-18). Subjects were divided into aggravation and non-aggravation of psychological stress groups according to the SRS-18. LUTS was evaluated according to the International Prostate Symptom Score (IPSS). Lower urinary tract function was evaluated as the post-void residual urine volume (PVR). Comparisons of scores and changes in scores of each parameter before versus during/after the first wave of the COVID-19 pandemic were performed between the two groups. RESULTS: Forty-two patients were included in each group. We observed no significant differences in the comparison of scores at each time point and in changes in total IPSS score, voiding symptom subscores and PVR between the two groups. Although no significant differences in storage symptom subscores were observed between the two groups, changes in storage symptom subscores increased significantly during the first wave of the pandemic in the aggravation of psychological stress group (p=0.02). However, no significant increase was observed after the first wave. CONCLUSION: Psychological stress during the COVID-19 pandemic might transiently aggravate storage symptoms in patients with LUTS. Physicians should be aware of the possibility of transient worsening of LUTS during future pandemics, and transiently additional medication might be effective in such patients.

Low Risk of Venous Thromboembolism After Robot-assisted Radical Prostatectomy Through Systemic Image Assessment: A Prospective Study.

BACKGROUND/AIM: The aim of the study was to evaluate the risk of venous thromboembolism (VTE) after robot-assisted radical prostatectomy (RARP) and discuss whether a uniform prophylaxis for VTE after radical prostatectomy is also suitable for robotic surgery. On this context, we investigated the incidence and risk factors of VTE, including asymptomatic events, after RARP compared to transurethral resection of bladder tumor (TUR-BT). PATIENTS AND METHODS: The participants were 209 patients with localized prostate cancer who underwent RARP, and 93 patients who underwent TUR-BT as controls. The incidence and risk factors of VTE, including deep vein thrombosis and pulmonary embolism, were systemically investigated seven days after surgery using contrast-enhanced computed tomography. RESULTS: Of the 209 RARP patients, 5.7% (12/209) patients had VTE. All events were asymptomatic and the incidence of VTE was not significantly different between the two surgeries (p=0.90). In multivariate analyses, neoadjuvant androgen deprivation therapy (ADT) (p=0.006), D-dimer value on postoperative day 1 (p=0.001) and lymphocele formation (p=0.043) were significantly associated with VTE after RARP. CONCLUSION: The risk of VTE after RARP might not be so high and uniform prophylaxis might not be suitable for RARP because it might be the same as that after transurethral resection for bladder tumors. However, neoadjuvant ADT, high D-dimer levels after surgery and lymphocele formation should be noted as risk factors of VTE after RARP.

Serum IgG4 Concentration Is a Potential Predictive Biomarker in Glucocorticoid Treatment for Idiopathic Retroperitoneal Fibrosis.

OBJECTIVES: To evaluate the management and outcome of idiopathic retroperitoneal fibrosis (iRPF) in Japan, and to identify its clinical biomarker. METHODS: We retrospectively analyzed 129 patients with iRPF treated between January 2008 and May 2018 at 12 university and related hospitals. Patients treated with glucocorticoid were analyzed to identify a predictive biomarker. These patients were classified into three groups according to overall effectiveness (no change: NC, complete response: CR, and partial response groups: PR), and each parameter was compared statistically. RESULTS: Male-female ratio was 5:1, and median age at diagnosis was 69 (33-86) years. Smoking history was reported in 59.6% of the patients. As treatment, 95 patients received glucocorticoid therapy with an overall response rate of 84%. As a result, serum concentration of IgG4 was significantly decreased in NC group compared with the other two groups (56.6 mg/dL vs. 255 mg/dL, 206 mg/dL, p = 0.0059 and 0.0078). ROC analysis was performed between the nonresponder (NC) and responder groups (CR + PR) to identify the cut-off value of serum IgG4 as a predictive marker. As a result, AUC of 0.793 was confirmed. CONCLUSIONS: Pre-treatment serum IgG4 concentration may have potential as a predictive biomarker of steroid treatment.

Efficacy of the opened legs position for protecting against postoperative rhabdomyolysis after robot-assisted radical prostatectomy: A propensity score-matched analysis of perioperative outcomes.

OBJECTIVES: The aim of the present study was to clarify the relationships of intraoperative surgical position with the incidence of postoperative rhabdomyolysis and with postoperative renal function to safely perform robot-assisted radical prostatectomy. METHODS: The participants in the present study were 276 consecutive patients who underwent robot-assisted radical prostatectomy at our institutions between 2013 and 2020; 130 cases were performed in the opened legs position and 146 cases in the lithotomy position with a steep 23°-25° head-down position. Rhabdomyolysis was defined as creatine kinase values greater than 1000 IU/L. Propensity score matching including age, body mass index, the presence of comorbidities, preoperative creatine kinase, preoperative estimated glomerular filtration rate, and prostate-specific antigen was performed, resulting in a matched cohort of 146 patients (opened legs position group n = 73; lithotomy position group n = 73). RESULTS: After propensity score matching, creatine kinase values on the first day after surgery were significantly lower in the opened legs position group than in the lithotomy position group (opened legs position group: lithotomy position group = 246.9 ± 114.9 IU/L: 558.2 ± 114.9 IU/L, P = 0.034). There were significantly fewer patients diagnosed with postoperative rhabdomyolysis in the opened legs position group (opened legs position group: lithotomy position group = 0% (0/73): 9.6% (7/73), P < 0.001). In addition, fluid replacement volume was significantly less in the opened legs position group (opened legs position group: lithotomy position group = 5747 ± 180 mL: 6349 ± 0176 mL, P = 0.018). CONCLUSIONS: To prevent rhabdomyolysis after surgery, robot-assisted radical prostatectomy should be performed in the opened legs position.

Impacts of Neoadjuvant Hormonal Therapy Prior to Robot-Assisted Radical Prostatectomy on Postoperative Hormonal- and Sexual-Related Quality of Life - Assessment by Patient-Reported Questionnaire.

PURPOSE: Neoadjuvant hormonal therapy (HT) before radical prostatectomy (RP) is not recommended by current guidelines in terms of oncological outcomes. Despite this, neoadjuvant HT is sometimes conducted before RP for a small proportion of patients in clinical practice. This study evaluated the impacts of neoadjuvant HT on hormonal- and sexual-related quality of life (QOL) among patients who underwent robot-assisted RP (RARP). MATERIALS AND METHODS: Participants comprised 470 patients divided into a non-neoadjuvant HT group (n = 408) and a neoadjuvant HT group (n = 62). Hormonal- and sexual-related QOL were measured using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. RESULTS: Hormonal summary scores at 6 and 9 months, function scores before and 3, 6, and 9 months and bother score at 6 months after RARP were significantly lower in the neoadjuvant HT group than in the non-neoadjuvant HT group. Sexual function scores were decreased in the neoadjuvant HT group compared to the non-neoadjuvant HT group before and 6 months after RARP. In the neoadjuvant HT group, sexual function at 3 months after RARP was significantly worse in patients with >5 months of neoadjuvant HT than in patients with ≤5 months of neoadjuvant HT. Conversely, sexual bother at 3 months after RARP was significantly worse in patients with ≤5 months of neoadjuvant HT than in patients with >5 months of neoadjuvant HT. CONCLUSION: Vintage neoadjuvant HT prior to RARP should not be recommended due to not only oncological outcomes, but also the impacts on postoperative hormonal- and sexual-related QOL.