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.

A kit ligand, stem cell factor as a possible mediator inducing overactive bladder.

OBJECTIVE: To investigate whether c-kit ligand, stem cell factor (SCF) affects the biological behavior of overactive bladder (OAB) and discuss the role of SCF as a possible mediator inducing OAB. MATERIALS AND METHODS: First, we performed an immunohistochemical study to examine the localization of SCF in the guinea pig and human bladder. Next, urinary SCF levels were measured in patients with OAB and in control subjects to evaluate a potential biomarker for the diagnosis of OAB. Third, we examined the effect of SCF administration on the urinary bladder using guinea pigs to obtain additional information about SCF. The animals were administered with mouse SCF, and cystometry was performed. The following urodynamic parameters were analyzed: inter-contraction interval, maximum voiding pressure, pressure threshold, detrusor baseline pressure, and the number of non-voiding contractions. RESULTS: Immunohistochemical study showed that the expression of SCF was observed throughout the bladder wall, but especially in the urothelium of guinea pig and human bladder. Medians and IQRs of urinary SCF and SCF/creatinine levels in OAB patients (85.9 pg/mL [42.8, 199.0] and 1.30 [0.56, 2.71], respectively) were significantly higher than in control subjects (18.9 pg/mL [5.0, 43.6] and 0.26 [0.13, 0.43], respectively). SCF administration dose-dependently shortened the intercontraction interval and an increased number of non-voiding contractions (P < 0.05). CONCLUSIONS: Our present data suggest that SCF produced in the urinary bladder may act as a possible mediator by binding to c-kit, which is expressed in ICC-like cells in the suburothelial and muscle layers, to control bladder function.

Potassium-sodium citrate prevents the development of renal microcalculi into symptomatic stones in calcium stone-forming patients.

OBJECTIVES: To evaluate the effect of potassium-sodium citrate on the development of computed tomography-detected renal microcalculi into symptomatic stones in calcium stone-forming patients. METHODS: Patients (aged 20-80 years) with history of calcium component stones who visited Nagoya City Hospital, Nagoya, Aichi, Japan, between April 2009 and June 2014 were included. They were retrospectively divided into those who did not receive potassium-sodium citrate (non-citrate group, n = 157) and those who did (citrate group, n = 60). For patients in both groups, we evaluated blood and urine biochemistry and sediment, number of computed tomography-detected microcalculi, number of asymptomatic microcalculi disappearances, and pain events. Observations were made at study initiation and 12 months later. RESULTS: The citrate group showed a significantly increased urine pH (P < 0.001) and daily citrate excretion (P < 0.001) over the study period. The non-citrate group showed increased numbers of microcalculi at study completion (P = 0.002); over the same period, the number of microcalculi in the citrate group decreased significantly (P = 0.03). Additionally, multivariable analysis showed more asymptomatic microcalculi disappearances (odds ratio 2.84, 95% confidence interval 1.49-5.39) and fewer pain events (odds ratio 0.37, 95% confidence interval 0.16-0.72) in the citrate group than in the non-citrate group. A sex-adjusted analysis showed more asymptomatic microcalculi disappearances (odds ratio 3.96, 95% confidence interval 1.57-10.02) and fewer pain events (odds ratio 0.22, 95% confidence interval 0.07-0.70) in women than in men after citrate treatment. CONCLUSIONS: Potassium-sodium citrate prevents the development of renal microcalculi into symptomatic stones in calcium stone-forming individuals.

Interleukin-18 may lead to benign prostatic hyperplasia via thrombospondin-1 production in prostatic smooth muscle cells.

BACKGROUND: Although inflammation plays an important role in the development of benign prostatic hyperplasia (BPH), little is known about the exact mechanism underlying this pathogenesis. Here, we investigated the relationship between the inflammatory reaction and BPH. METHODS: cDNA microarray analysis was used to identify changes in inflammation-related gene expression in a recently established rat model that mimics human BPH. To investigate the genes identified in the analysis, quantitative (q)RT-PCR, Western blotting, immunostaining, and a cell proliferation assay were conducted using BPH model tissues, human prostate tissues, and normal human prostate cultured cells. RESULTS: Of the 31,100 genes identified in the cDNA analysis, seven inflammatory-response-related genes were expressed at a >2-fold higher level in rat BPH tissues than in normal rat prostate tissues. The levels of the most commonly expressed pro-inflammatory cytokine, IL-18, significantly increased in rat BPH tissues. In humans, IL-18 was localized in the epithelial and stromal components, while its receptor was strongly localized in smooth muscle cells. Furthermore, in human prostate smooth muscle cell line (PrSMC), IL-18 effected dose-dependent increases in the phosphorylated Akt and thrombospondin-1 (TSP-1) levels. TSP-1 promoted proliferation of the human prostate stromal cells (PrSC). CONCLUSIONS: IL-18 may act directly in BPH pathogenesis by inducing TSP-1 production in prostatic smooth muscle cells via Akt phosphorylation.

Novel effect of the inhibitor of mitochondrial cyclophilin D activation, N-methyl-4-isoleucine cyclosporin, on renal calcium crystallization.

OBJECTIVES: To experimentally evaluate the clinical application of N-methyl-4-isoleucine cyclosporin, a novel selective inhibitor of cyclophilin D activation. METHODS: In vitro, cultured renal tubular cells were exposed to calcium oxalate monohydrate crystals and treated with N-methyl-4-isoleucine cyclosporin. The mitochondrial membrane was stained with tetramethylrhodamine ethyl ester perchlorate and observed. In vivo, Sprague-Dawley rats were divided into four groups: a control group, an ethylene glycol group (administration of ethylene glycol to induce renal calcium crystallization), a N-methyl-4-isoleucine cyclosporin group (administration of N-methyl-4-isoleucine cyclosporin) and an ethylene glycol + N-methyl-4-isoleucine cyclosporin group (administration of ethylene glycol and N-methyl-4-isoleucine cyclosporin). Renal calcium crystallization was evaluated using Pizzolato staining. Oxidative stress was evaluated using superoxide dismutase and 8-hydroxy-deoxyguanosine. Mitochondria within renal tubular cells were observed by transmission electron microscopy. Cell apoptosis was evaluated using cleaved caspase-3. RESULTS: In vitro, calcium oxalate monohydrate crystals induced depolarization of the mitochondrial membrane potential, which was remarkably prevented by N-methyl-4-isoleucine cyclosporin. In vivo, ethylene glycol administration induced renal calcium crystallization, oxidative stress, mitochondrial collapse and cell apoptosis in rats, which were significantly prevented by N-methyl-4-isoleucine cyclosporin. CONCLUSIONS: Herein we first report a new treatment agent determining renal calcium crystallization through cyclophilin D activation.

Kidney stone formation is positively associated with conventional risk factors for coronary heart disease in Japanese men.

PURPOSE: We investigated the association between kidney stones and coronary heart disease risk factors in Japanese men. MATERIALS AND METHODS: This cross-sectional study included 13,418 Japanese men 30 to 69 years old who voluntarily underwent medical examination between April 1995 and March 2001. Participants were divided into controls, and past and current kidney stone formers based on ultrasound results and medical history. We evaluated conventional risk factors of coronary heart disease, including overweight/obesity, hypertension, diabetes mellitus, gout/hyperuricemia, dyslipidemia and chronic kidney disease. Associations between coronary heart disease risk factors and kidney stones were investigated. RESULTS: Of the 13,418 participants 404 current kidney stone formers (3.0%) had kidney stones on ultrasound and 1,231 past kidney stone formers (9.2%) had a history of kidney stones but no kidney stones on medical examination. Body mass index, systolic and diastolic blood pressure, and serum uric acid were significantly higher in past and current kidney stone formers than in controls. Logistic regression analysis indicated that the multivariate adjusted OR for overweight/obesity, hypertension, gout/hyperuricemia and chronic kidney disease significantly increased in the order corresponding to controls, and past and current kidney stone formers. CONCLUSIONS: Kidney stone formers, even past stone formers, are likely to have accumulated risk factors for coronary heart disease. They could be preferentially targeted for coronary heart disease prevention.

A replication study for three nephrolithiasis loci at 5q35.3, 7p14.3 and 13q14.1 in the Japanese population.

A previous genome-wide association study (GWAS) reported three novel nephrolithiasis-susceptibility loci at 5q35.3, 7p14.3 and 13q14.1. Here, we investigated the association of these loci with nephrolithiasis by using an independent Japanese sample set. We performed case-control association analysis using 601 patients with nephrolithiasis and 201 control subjects. We selected seven single-nucleotide polymorphisms (SNPs): rs12654812 and rs11746443 from 5q35.3 (RGS14-SLC34A1-PFN3-F12); rs12669187 and rs1000597 from 7p14.3 (INMT-FAM188B-AQP1); and rs7981733, rs1170155, and rs4142110 from 13q14.1 (DGKH (diacylglycerol kinase)), which were previously reported to be significantly associated with nephrolithiasis. rs12654812, rs12669187 and rs7981733 were significantly associated with nephrolithiasis after Bonferroni's correction (P=3.12 × 10(-3), odds ratio (OR)=1.43; P=6.40 × 10(-3), OR=1.57; and P=5.00 × 10(-3), OR=1.41, respectively). Meta-analysis of current and previous GWAS results indicated a significant association with nephrolithiasis (P=7.65 × 10(-15), 7.86 × 10(-14) and 1.06 × 10(-9), respectively). We observed a cumulative effect with these three SNPs; individuals with three or more risk alleles had a 5.9-fold higher risk for nephrolithiasis development than those with only one risk allele. Our findings elucidated the significance of genetic variation at these three loci in nephrolithiasis in the Japanese population.

Postoperative Bladder Neck to Pubic Symphysis Ratio Predictive for De Novo Overactive Bladder after Robot-Assisted Radical Prostatectomy.

BACKGROUND: The aim was to investigate the incidence and clinical predictive factors of de novo overactive bladder (OAB) after robot-assisted radical prostatectomy (RARP), including a Retzius-sparing (RS) approach, in the same period at a single institution. METHODS: Of a total of 113 patients with localized prostate cancer, 81 received conventional RARP (CON-RARP) and 32 received RS-RARP at our institution. The basic characteristics data of patients and self-assessment questionnaires, including IPSS and OABSS, were obtained preoperatively and 1, 3, and 6 months after RARP. In addition, a retrospective biomarker analysis was also performed of predictive clinical parameters obtained from cystography that included a postoperative bladder neck to pubic symphysis (BNPS) ratio. RESULTS: Patients' basic characteristics were similar between CON-RARP and RS-RARP groups. With respect to the surgical procedure, anastomosing time was found to be significantly longer for patients in the RS-RARP compared to the CON-RARP group (p < 0.01). Compared to the CON-RARP group, the RS-RARP group showed a significantly lower postoperative BNPS and aspect ratio (p < 0.001). The incidence of de novo OAB in patients of the CON-RARP group was greater than for those in the RS-RARP group (40.7% CON-RARP vs. 25.0% RS-RARP), though this was not significant. Regarding the emergence of de novo OAB, the following were revealed in univariate analysis to be independent prognostic factors: age > 64 years (hazards ratio [HR]: 4.32, 95% confidence interval [CI]: 1.51-12.3), postoperative BNPS ratio > 0.44 (HR: 8.7, 95% CI: 6.43-54.5), postoperative aspect ratio > 1.18 (HR: 3.36, 95% CI: 1.49-7.61). Additionally, multivariate analysis identified a sole significant prognostic factor: postoperative BNPS ratio > 0.44 (HR: 13.3, 95% CI: 4.33-41.1). CONCLUSION: Our findings indicate that the postoperative BNPS ratio may be a practical predictive indicator of the emergence of de novo OAB after RARP.

Regulation of cell proliferation through a KIT-mediated mechanism in benign prostatic hyperplasia.

BACKGROUND: We investigated the role of the KIT-mediated mechanism in benign prostatic hyperplasia (BPH), and discuss the pathophysiology of BPH and a candidate target of BPH medical therapy. METHODS: We performed RT-PCR, Western blotting, and immunohistochemistry to examine the expression of KIT in the prostate using a human prostate stromal cell line (PrSC) and human prostate. To investigate the pathophysiological function of KIT, the effects of KIT ligand, stem cell factor (SCF), and imatinib mesylate on cell proliferation were investigated using PrSC. Additionally, we compared the expression level and distribution of KIT in normal prostate and BPH of humans to clarify the contribution of KIT to the pathogenesis of BPH. RESULTS: KIT was expressed in PrSC and human prostate, indicating that these samples are suitable for examining the function of KIT. Immunohistochemical analysis demonstrated that KIT was localized in interstitial cells (ICs) of the stromal component in human prostate. Administration of imatinib mesylate dose-dependently inhibited cell proliferation of PrSC with downregulation of JAK2 and STAT1, which are the main pathways downstream of SCF/KIT signal. SCF promoted cell proliferation of PrSC with upregulation of JAK2 and STAT1. KIT expression and the number of KIT-positive ICs in BPH were found to be significantly larger than in normal prostate. CONCLUSIONS: This is the first report to suggest that KIT regulates cell proliferation in the prostate and plays a significant role in the pathophysiology of BPH. Our study may lead to a greater understanding of the mechanism of BPH and provide a therapeutic target.

Tamsulosin reduces nighttime urine production in benign prostatic hyperplasia patients with nocturnal polyuria: a prospective open-label long-term study using frequency-volume chart.

AIMS: The effects of tamsulosin treatment on changes in frequency-volume chart (FVC) data, especially nighttime urine production, over time were assessed, and the mechanisms underlying the improvement of nocturia in benign prostatic hyperplasia (BPH) patients with nocturnal polyuria (NP) are discussed. METHODS: A total of 104 patients with lower urinary tract symptoms secondary to BPH were enrolled. After enrollment in the study, the patients were treated with tamsulosin (0.2 mg) once daily. Visits were scheduled every 4 weeks until week 12 (month 3) after study entry, and then every 12 weeks subsequently. All patients completed the International Prostate Symptom Score (IPSS), quality of life (QOL) index, and 3-day FVC, and underwent uroflowmetry at enrollment and on each visit. RESULTS: Eighty-two patients (mean age: 70.9 ± 7.1 years) were analyzed for 24 months after treatment. Patients were divided into two groups, NP and nonNP, based on FVC outcome. The IPSS, QOL index, and maximum flow rate improved during the 24-month period after treatment in both groups. Mean daytime urine volume significantly increased in the NP group, but no changes were detected in the nonNP group. Mean nighttime urine frequency significantly decreased in the NP group over a 24-month period, and was associated with a significant decrease in nighttime urine volume that was not found in the nonNP group. Maximum voided volume increased most months after treatment in both groups. CONCLUSIONS: The present long-term prospective study using FVC demonstrated that tamsulosin reduced nighttime urine production in BPH patients with NP.

Role of osteopontin in early phase of renal crystal formation: immunohistochemical and microstructural comparisons with osteopontin knock-out mice.

Osteopontin (OPN) is an important matrix protein of renal calcium stone. However, the function of OPN in the early phase of renal crystal formation is not well defined. In this study, we examined OPN expression in the early phase of renal crystal formation with ultra-microstructural observations and immuno-TEM (transmission electron microscopy) in control and OPN knock-out (OPN-KO) mice. Glyoxylate (100 mg/kg) was intra-abdominally administered to male wild-type mice (C57BL/6, 8 weeks of age) and OPN-KO mice (C57BL/6, 8 weeks of age). Kidney was collected before and 6, 12, and 24 h after administration. We examined the relation between renal crystal formation and microstructural OPN location using TEM and immunohistochemical staining of OPN as well as western blotting and quantitative RT-PCR for OPN. OPN protein expression gradually increased in the renal cortex-medulla junction after glyoxylate administration, and OPN mRNA was increased until 12 h, but decreased at 24 h. In ultra-microstructural observation, OPN began to appear on the luminal side of renal distal tubular cells at 6 h and was gradually detected in the tubular lumen at 12 h. OPN was present in the crystal nuclei and collapsed mitochondria in the tubular lumen. In the OPN-KO mice, collapsed mitochondria were present, but no crystal nuclei formation were detected at 24 h. Based on the results this study proposed that the appearance of organelles, such as mitochondria and microvilli, in the tubular lumen after cell injury may be the starting point of crystal nucleus formation due to the aggregation ability of OPN.

Up-regulation of α1a and α1d-adrenoceptors in the prostate by administration of subtype selective α1-adrenoceptor antagonist tamsulosin in patients with benign prostatic hyperplasia.

PURPOSE: We examined the change in α(1)-adrenoceptor subtype expression in the prostate due to chronic tamsulosin administration in a benign prostatic hyperplasia rat model and in patients. MATERIALS AND METHODS: We measured α(1)-adrenoceptor subtype expression after tamsulosin administration in the prostate of the benign prostatic hyperplasia rat model using TaqMan® reverse transcriptase-polymerase chain reaction. We also measured expression before and after 12-week tamsulosin treatment in the prostate of patients with benign prostatic hyperplasia. We examined the correlation between the change in α(1)-adrenoceptor expression due to tamsulosin treatment and acute urinary retention during long-term followup. RESULTS: The expression of α(1a) and α(1d)-adrenoceptors was significantly increased in dose dependent fashion by tamsulosin in the benign prostatic hyperplasia rat model. Median mRNA expression of subtypes α(1a) and α(1d)-adrenoceptors was 1.4 (IQR 0.6, 3.0) and 1.7 × 1,000 copies per 1 ng ß-actin (IQR 0.9, 2.4) before treatment, and 6.0 (IQR 2.0, 8.0) and 2.2 × 1,000 copies per 1 ng ß-actin (IQR 1.7, 3.6), respectively, after treatment. The expression of α(1a) and α(1d)-adrenoceptors significantly increased after tamsulosin treatment (p <0.01 and <0.05, respectively). This increase was observed in 10 patients in whom acute urinary retention did not develop during long-term followup but not in 4 in whom acute urinary tract retention developed. CONCLUSIONS: Tamsulosin up-regulated α(1a) and α(1d)-adrenoceptors, suggesting that it has clinical selectivity for α(1a) and α(1d)-adrenoceptors. Up-regulation of α(1)-adrenoceptors subtype expression is considered an adaptive response to chronic tamsulosin administration. The difference in the response to α(1)-adrenoceptors antagonists among patients may contribute to the diversity in the long-term efficiency of α(1)-adrenoceptor antagonists.

Correlation between expression of α1-adrenoceptor subtype mRNA and severity of lower urinary tract symptoms or bladder outlet obstruction in benign prostatic hyperplasia patients.

OBJECTIVE: To examine whether the direct correlation between the expression of α1-adrenoceptor (AR) subtype mRNA and severity of lower urinary tract symptoms (LUTS) or bladder outlet obstruction (BOO) in the prostate exists in benign prostatic hyperplasia (BPH) patients. PATIENTS AND METHODS: Sixty-eight patients with LUTS and BOO secondary to BPH were enrolled. Four prostate needle biopsy specimens were obtained from the transition zone to examine the expression level of α1-AR subtypes by Taqman reverse-transcription polymerase chain reaction. The correlation and regression between each expression level of α1-AR subtype and clinical findings such as patient age, prostate volume, International Prostate Symptom Score (IPSS), quality of life (QOL) index, maximum flow rate in uroflowmetry (Qmax) and post-void residual urine volume (PVR) were assessed by stepwise multiple regression analysis. The correlation and regression between this expression level and individual symptoms of IPSS were assessed by Pearson's correlation coefficient and multiple regression analyses. RESULTS: Stepwise multiple regression analysis showed that the expression levels of α(1a) -AR, α(1b) -AR, α(1d) -AR and total α(1) -AR mRNA showed a significant regression with patient age, but not with prostate volume, IPSS, QOL index, Qmax and PVR. Pearson's correlation coefficient and multiple regression analyses demonstrated no correlation and regression between each α(1) -AR subtype mRNA expression level and individual symptoms of IPSS. CONCLUSIONS: There was no direct correlation between the expression of α1-AR subtype mRNA in the prostate and severity of LUTS or BOO in BPH patients, although the significant regression of this expression with patient age existed. LUTS and BOO may be associated with multiple factors and several other conditions may contribute to LUTS and BOO.

Attenuation of bladder overactivity in KIT mutant rats.

OBJECTIVES: To investigate morphological and physiological findings in the bladder of KIT mutant (WsRCWs/Ws) rats to clarify whether the disturbance of KIT pathways affects bladder activity. To discuss the potential role of KIT-positive interstitial cells of Cajal (ICC)-like cells in the urinary bladder. MATERIALS AND METHODS: Reverse transcriptase-polymerase chain reaction and western blotting was used to confirm the absence of c-kit mRNA and protein in the bladders of 12-week-old WsRCWs/Ws rats. Light and transmission electron microscopy was used to identify the differences in morphological and ultrastructural characteristics of the bladder between WsRCWs/Ws and wild-type (WsRC+/+) rats. The voiding pattern of WsRCWs/Ws rats and the effects of cyclophosphamide (CYP) and protamine sulphate on bladder function were examined using cystometry. RESULTS: In WsRC+/+ rats, c-kit mRNA and KIT protein expression were observed in the urinary bladder, while they were not detectable in WsRCWs/Ws rats. Deformation of ICC-like cells with the collapse of the organelle was not observed in the bladders of WsRCWs/Ws rats. Each cystometry variable in WsRCWs/Ws rats was similar to that in WsRC+/+ rats. The reduction in the intercontraction intervals in WsRCWs/Ws rats with chemically (CYP and protamine sulphate) induced cystitis was significantly lower than in WsRC+/+ rats (P < 0.05). CONCLUSION: Certain voiding disturbances might be associated with impaired KIT signalling in ICC-like cells, therefore, KIT could be a candidate target for medical therapy in the future.

Correlation between improvements in Overactive Bladder Symptom Score and health-related quality of life questionnaires in overactive bladder patients treated with an antimuscarinic drug.

AIMS: To evaluate the relationship between treatment-related changes in Overactive Bladder Symptom Scores (OABSS) and health-related quality of life (HRQOL) questionnaires. METHODS: Ninety-five patients with OAB symptoms were enrolled. All patients completed the OABSS, International Prostate Symptom Score (IPSS)-Quality Of Life (QOL) index and King's Health Questionnaire (KHQ) at enrollment and then again 4, 8, and 12 weeks after treatment with propiverine hydrochloride 10 mg twice daily. We evaluated the relationship between treatment-related changes in the OABSS, IPSS-QOL, and KHQ. RESULTS: Statistically significant improvements were observed in all 4 OABSS subscales and total OABSS from baseline to 4 weeks with further improvements occurring at 12 weeks (all P < 0.01). The OABSS after antimuscarinic treatment correlated positively with both the IPSS-QOL index and KHQ domain scores. There was a moderate but statistically significant correlation between the change in total OABSS and 2 OABSS subscales (urinary urgency and urge incontinence) and improvement in the IPSS-QOL index (P < 0.01). Treatment-related changes in total OABSS were significantly correlated with changes in six KHQ domains. Moderate but statistically significant correlations were observed between the change in total OABSS and impact on life, physical limitations, emotions, and severity measures (r > 0.30, P < 0.05). Small but statistically significant correlations were observed between the change in total OABSS and role limitations or social limitations (P < 0.05). CONCLUSIONS: Improvement in the OABSS correlated with improvements in HRQOL after treatment. The OABSS is a useful tool to evaluate OAB symptom severity after medical treatment.

Novel case of androgen receptor-positive cancer of unknown primary without serum prostate-specific antigen elevation that became progression free in the long term after primary combined androgen blockade.

INTRODUCTION: The prognosis of cancer of unknown primary is very poor. Such a prognosis can be improved by characterizing primary characteristics and developing tailored site-specific therapy, especially for androgen receptor-positive adenocarcinoma. However, in such cases without elevated prostate-specific antigen, the efficacy of androgen deprivation therapy is unclear. CASE PRESENTATION: Herein, we report a case that presented with a retroperitoneal cancer of unknown primary that was confirmed as an androgen receptor-positive adenocarcinoma without prostate-specific antigen elevation. Pelvic magnetic resonance imaging did not reveal any suspicious cancer lesions in the prostate. Furthermore, malignant cells were not present in a prostate biopsy specimen. In spite of the prostate-specific antigen level, on the basis of immunohistochemical analyses, including NKX3.1, the patient was first treated with androgen deprivation therapy, leading to long-term progression-free survival. CONCLUSION: Early androgen deprivation therapy based on immunohistochemical analyses might lead to a good outcome in androgen receptor-positive adenocarcinoma cancer of unknown primary patients regardless of prostate-specific antigen level.

Change in the central control of the bladder function of rats with focal cerebral infarction induced by photochemically-induced thrombosis.

The photochemically-induced thrombosis (photothrombosis) method can create focal cerebral infarcts anywhere in the relatively superficial layers of the cerebrum; it is easy to implement and minimally invasive. Taking advantage of this versatility, we aimed to establish a new rat model of urinary frequency with focal cerebral infarction, which was characterized by its simplicity, nonlethal nature, and high reproducibility. The prefrontal cortex and the anterior cingulate cortex, which are involved in lower urinary tract control, were targeted for focal cerebral infarction, and urinary parameters were measured by cystometrogram. Cystometric analysis indicated that micturition intervals significantly shortened in photothrombosis-treated rats compared with those in the sham operative group on Days 1 and 7 (P < 0.01), but prolonged after 14 days, with no difference between the two groups. Immunopathological evaluation showed an accumulation of activated microglia, followed by an increase in reactive astrocytes at the peri-infarct zone after photothrombotic stroke. Throughout this study, all postphotothrombosis rats showed cerebral infarction in the prefrontal cortex and anterior cingulate cortex; there were no cases of rats with fatal cerebral infarction. This model corresponded to the clinical presentation, in that the micturition status changed after stroke. In conclusion, this novel model combining nonlethality and high reproducibility may be a suitable model of urinary frequency after focal cerebral infarction.

Pelvic Anatomical Features After Retzius-Sparing Robot-Assisted Radical Prostatectomy Intended for Early Recovery of Urinary Symptoms.

Purpose: To elucidate factors contributing to early urinary continence recovery after retzius-sparing robot-assisted radical prostatectomy (RS-RARP) by evaluating postoperative pelvic anatomical features between RS-RARP and conventional RARP (CON-RARP). Materials and Methods: We retrospectively examined 50 men who underwent RS-RARP (n = 25; the RS-RARP group) and CON-RARP (n = 25; the CON-RARP group) between October 2017 and June 2018. Perioperative outcomes and postoperative urinary continence were assessed in both groups. Anatomical features including the bladder neck-to-pubic symphysis ratio (determined from cystograms) and membranous urethral length (MUL) (determined from magnetic resonance imaging) were evaluated. Result: The daily urinary incontinence rate at discharge was significantly lower in the RS-RARP group than in the CON-RARP group (0.046 [range: 0.014-0.160] vs 0.357 [range: 0.139-0.616], p < 0.001). Postoperative urinary continence at 1, 3, 6, and 12 months was 80%, 92%, 96%, and 96% in the RS-RARP group and 24%, 40%, 68%, and 84% in the CON-RARP group, respectively (p < 0.001). The urgency scores in the international prostate symptom score (IPSS) questionnaire at 1 and 3 months were significantly lower in the RS-RARP than in the CON-RARP group (p = 0.028 and 0.033, respectively). The quality of life (QOL) indices were more significantly improved in the RS-RARP group than in the CON-RARP group 1 month (p = 0.027) and 3 months (p = 0.045) postoperatively. Receiver operating characteristic analysis revealed that a postoperative MUL of 12.1 mm (area under the curve: 0.852) was the optimal cutoff value predictive of continence recovery after 1 month. Multivariate analysis demonstrated that RS-RARP (odds ratio [OR]: 23.6; p < 0.001) and prostate volume (OR: 0.926; p = 0.049) were the independent factors of a longer MUL. Conclusions: RS-RARP results in an early continence recovery and a better urgency score in the IPSS by suppressing the descent of the bladder and maintaining a long MUL. RS-RARP may contribute to a better QOL recovery after RARP.

Characterization of Streptococcus pyogenes isolated from balanoposthitis patients presumably transmitted by penile-oral sexual intercourse.

Streptococcus pyogenes is indigenous to the human pharynx and causes acute pharyngitis. Balanoposthitis is an inflammatory disease of the glans and the foreskin. However, balanoposthitis caused by S. pyogenes is not widely recognized as a sexually transmitted disease. In addition, bacteriological features of the isolates causing balanoposthitis are unclear. The four S. pyogenes strains isolated from adult balanoposthitis were examined. We performed emm typing, T antigen typing, RAPD assay, PCR assay for the streptococcal pyrogenic exotoxin-related genes and antibiotic-resistant genes, and antibiotic susceptibility assay. All four strains were suspected to be transmitted by penile-oral sexual intercourse, were found to be different by genetic analysis, and also harbored some antibiotic-resistant factors. We propose that S. pyogenes should be considered as a causative agent of sexually transmitted disease. The drug resistant S. pyogenes must be taken into account when balanoposthitis patients are treated with antibiotic.