Sex differences in lower urinary tract function in mice with or without spinal cord injury.

OBJECTIVES: We examined sex differences of lower urinary tract function and molecular mechanisms in mice with and without spinal cord injury (SCI). METHODS: SCI was induced by Th8-9 spinal cord transection in male and female mice. We evaluated cystometrograms (CMG) and electromyography (EMG) of external urethral sphincter (EUS) at 6 weeks after SCI in spinal intact (SI) and SCI mice. The mRNA levels of Piezo2 and TRPV1 were measured in L6-S1 dorsal root ganglia (DRG). Protein levels of nerve growth factor (NGF) in the bladder mucosa was evaluated using an enzyme-linked immunosorbent assay. RESULTS: Sex differences were found in the EUS behavior during voiding as voiding events in female mice with or without SCI occurred during EUS relaxation periods without EUS bursting activity whereas male mice with or without SCI urinated during EUS bursting activity in EMG recordings. In both sexes, SCI decreased voiding efficiency along with increased tonic EUS activities evident as reduced EUS relaxation time in females and longer active periods of EUS bursting activity in males. mRNA levels of Piezo2 and TRPV1 of DRG in male and female SCI mice were significantly upregulated compared with SI mice. NGF in the bladder mucosa showed a significant increase in male and female SCI mice compared with SI mice. However, there were no significant differences in Piezo2 or TRPV1 levels in DRG or NGF protein levels in the bladder mucosa between male and female SCI mice. CONCLUSIONS: We demonstrated that female and male mice voided during EUS relaxation and EUS bursting activity, respectively. Also, upregulation of TRPV1 and Piezo2 in L6-S1 DRG and NGF in the bladder could be involved in SCI-induced lower urinary tract dysfunction in both sexes of mice.

Outcome of primary androgen deprivation therapy in super-elderly men with localized high-risk prostate cancer.

The purpose of this study is to provide certain data on clinical outcome of primary androgen deprivation therapy in men over 80 years of age with localized high-risk prostate cancer. This study included 54 Japanese super-elderly men with high-risk prostate cancer treated with primary androgen deprivation therapy between 2005 and 2015. The median overall survival was 9.1 years (95% confidence interval, 8.1-10.1) and no patient died from prostate cancer. Overall, 51.9% of patients experienced any grade of adverse events following androgen deprivation therapy. Associations between clinicopathological factors including comorbidity count at initial diagnosis and overall survival were investigated. On multivariate analysis, only comorbidity count at initial diagnosis [≥2 vs. ≤1; hazard ratio, 5.34 (95% confidence interval, 1.55-18.49); P = 0.003] was an independent risk factor for overall survival. Our findings suggest that comorbidity count at initial diagnosis is robustly prognostic for overall survival. For super-elderly men with localized high-risk prostate cancer, comorbidity count at initial diagnosis should be emphasized when deciding whether primary androgen deprivation therapy is necessary or not.

A new nomogram of urinary flow rate and volume based on multiple measurements per healthy adult Japanese men using a portable uroflowmeter (P-Flowdiary®).

BACKGROUND: To develop a nomogram of urinary volume and flow based on the data of Japanese men without lower urinary tract symptoms and multiple flows per participant whose characteristics were clear. METHODS: Overall, 101 Japanese male volunteers without lower urinary tract symptoms aged between 20 and 59 years were enrolled. A portable uroflowmeter (P-Flowdiary®) was used to record urinary information (flow rate and volume) for 2 successive days. The model (quadratic, linear, or logarithmic regression) most fit for the relationship between maximum flow rate and voided volume was determined. The maximum flow rate at > 150 mL was compared among the 20-29-, 30-39-, 40-49-, and 50-59-year age groups. Nomograms appropriate for the age groups were created. RESULTS: The mean age, International Prostate Symptom Score, and Overactive Bladder Symptom Score were 38.5 years, 0.42, and 0.24, respectively. The quadratic regression model was the most fit because its mean coefficient determination was 0.93 ± 0.06. The mean maximum flow rate was significantly lower in the 50-59-year age group (21.8 ± 5.05 mL/s, P < 0.01) than in the younger groups (24.14 ± 4.94, 24.05 ± 6.99, and 24.64 ± 5.72 mL/s). The 2 nomograms are Y = 28.99 {1 - exp(- 0.01 × X)} and Y = 25.67 {1 - exp(- 0.01 × X)} for the 20-49- and 50-59-year age groups, respectively. CONCLUSIONS: The nomogram can predict maximum flow rate based on voided volume in Japanese men aged 20-59 years without lower urinary tract symptoms.

Efficacy of vibegron, a novel ß3-adrenoreceptor agonist, for lower urinary tract dysfunction in mice with spinal cord injury.

OBJECTIVES: To investigate the effect of vibegron, a new clinically approved ß3-adrenoceptor agonist in lower urinary tract dysfunction in mice with spinal cord injury. METHODS: Investigators performed cystometry under awake conditions in 4-week spinal cord injury female mice. Two weeks after spinal cord injury, saline or vibegron (30 mg/kg) was orally administered for 2 weeks prior to the urodynamic study. Investigators removed L6-S1 dorsal root ganglia from the saline- or vibegron-treated spinal cord injury mice as well as from saline-treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase transcripts using real-time polymerase chain reaction. RESULTS: In vibegron-treated spinal cord injury mice, nonvoiding contractions during bladder filling, which were increased in spinal cord injury compared to spinal intact mice, were significantly decreased. Micturition pressure or voiding efficiency was not significantly increased in comparison to measurements in saline-treated spinal cord injury mice. The expression of transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, activating transcription factor 3, and inducible nitric oxide synthase messenger RNA was increased in spinal cord injury mice compared to spinal intact mice, but significantly decreased after vibegron treatment. CONCLUSIONS: Vibegron improves spinal cord injury-induced detrusor overactivity in addition to significantly reducing C-fiber afferent receptors such as transient receptor potential cation channel subfamily V member 1, transient receptor potential cation channel subfamily A member 1, and inflammatory cytokines/markers, such as activating transcription factor 3 and inducible nitric oxide synthase, in spinal cord injury mice. Thus, vibegron might be effective in the treatment of storage lower urinary tract dysfunction induced by C-fiber afferent activation after spinal cord injury.

Daily salt intake is associated with leg edema and nocturnal urinary volume in elderly men.

AIMS: There is accumulating evidence that excessive salt intake contributes to nocturnal polyuria. We aimed to investigate the relationship between salt intake, leg edema, and nocturnal urine volume (NUV) to assess the etiology of nocturnal polyuria. METHODS: A total of 56 men aged ≥60 years who were hospitalized for benign prostatic hyperplasia or with suspected prostatic cancer were enrolled. Urine frequency-volume charts of the patients were maintained, and they underwent bioelectrical impedance analysis twice daily (at 5:00 pm and 6:00 am) and examination of blood (brain natriuretic peptide levels) and urine (sodium and creatinine levels and osmotic pressure) samples once daily (at 6:00 am). Free-water clearance, solute clearance, and sodium clearance at night were measured, and daily salt intake was estimated. RESULTS: The data of 52 patients were analyzed. Daily salt intake positively correlated with leg edema at 5:00 pm, differences in leg extracellular fluid levels between 5:00 pm and 6:00 am, and NUV, but not with diurnal urine volume. Partial correlation coefficients showed that salt intake was a factor of the correlation between NUV and change in extracellular volume in the legs between 5:00 pm and 6:00 am. A multivariate logistic model showed that sleep duration and sodium clearance were independent predictive factors for nocturnal polyuria. CONCLUSIONS: Sodium intake correlates with diurnal leg edema and NUV in elderly men. These results provide evidence supporting sodium restriction as an effective treatment for nocturnal polyuria.

Role of p38 MAP kinase signaling pathways in storage and voiding dysfunction in mice with spinal cord injury.

AIM: To investigate the role of p38 MAP kinase in lower urinary tract dysfunction in mice with spinal cord injury (SCI). METHODS: Cystometry and external urethral sphincter-electromyography were performed under an awake condition in 4-week SCI female mice. Two weeks after SCI, a catheter connected to an osmotic pump filled with a p38 mitogen-activated protein kinase (MAPK) inhibitor or artificial cerebrospinal fluid (CSF) was implanted into the intrathecal space of L6-S1 spinal cord for continuous intrathecal instillation at infusion rate of 0.51 µL/h for 2 weeks before the urodynamic study. L6 dorsal root ganglia were then removed from CSF and p38 MAPK inhibitor-treated SCI mice as well as from CSF-treated normal (spinal intact) mice to evaluate the levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) transcripts by real-time polymerase chain reaction. RESULTS: In p38 MAPK inhibitor-treated SCI mice, nonvoiding contractions during bladder filling, bladder capacity, and post-void residual volume were significantly reduced while micturition pressure and voiding efficiency were significantly increased in comparison to these measurements in CSF-treated SCI mice. The expression of TRPV1, TNF-α, and iNOS messenger RNA was increased in SCI mice compared with expression in spinal intact mice and significantly decreased after p38 MAPK inhibitor treatment. CONCLUSIONS: The p38 MAPK signaling pathway in bladder sensory neurons or in the spinal cord plays an important role in storage and voiding problems such as detrusor overactivity and inefficient voiding after SCI.

Aquaporin-2 plays an important role in water transportation through the bladder wall in rats.

AIM: We investigated the role of the bladder wall in permeating water, focusing on aquaporins. METHODS: Female Sprague-Dawley rats weighing 300 g were used to investigate the role of the bladder wall in saline permeation. Changes in intravesical fluid volume and sodium concentration were measured in the desmopressin acetate hydrate-loaded and control groups 3 h after administration. Bladders were resected to measure aquaporin-1, 2, and 3 gene expression using qRT-PCR. Additionally, the change of aquaporin-2 expression was measured using Western blotting and immunohistochemistry in intravesical aquaporin-2 siRNA-treated and control groups. RESULTS: Although the intravesical fluid volume and sodium concentration significantly decreased from 0 to 3 h (1.00 ± 0.00 vs 0.83 ± 0.08 mL, 157.80 ± 1.30 vs 146.8 ± 1.92 mEq/mL, P < 0.01, respectively in the control group), administration of desmopressin did not affect the extent of volume change. Aquaporin-2 expression was significantly higher in the 3-h distended bladders than in the empty bladder. Aquaporin-2 siRNA treatment suppressed aquaporin-2 expression and the change of intravesical fluid volume from 0 to 3 h (1.00 ± 0.00 and 0.99 ± 0.02 mL), which was related to the suppression of sodium concentration change in comparison with control siRNA treatment (149.6 ± 2.4 vs 143.6 ± 3.67 mEq/mL, P < 0.05). CONCLUSIONS: The rat urinary bladder absorbs water and salts under the full-filled condition. Aquaporin-2 plays an important role in the transport of water, accompanied by sodium concentration change. We demonstrated a part of the bladder absorption mechanism, which may lead to development of a new method for regulating bladder storage function.

Tadalafil, a phosphodiesterase type 5 inhibitor, improves bladder blood supply and restores the initial phase of lower urinary tract dysfunction in diabetic rats.

AIMS: To investigate the effect of tadalafil on bladder blood flow and lower urinary tract function in a rat model of diabetes. MATERIALS AND METHODS: We studied female Sprague-Dawley rats and induced diabetes in some using a single intraperitoneal injection of streptozotocin. We divided the rats into nondiabetes (ND), diabetes (D), and diabetes with tadalafil (DT) groups. The rats were raised for an additional 7 weeks after diabetes induction. The DT group received oral tadalafil (2 mg/kg/day) for 7 days before the experiments. At 7 weeks after diabetes induction, we performed cystometry, resected the bladders for immunohistochemistry (hypoxia-inducible factor-1α [HIF-1α] and 8-oxo-2'-deoxyguanosine [8-OHdG] staining), and measured bladder blood supply using a laser blood flow meter. RESULTS: The opening pressure, when the urethra opens and urine flow starts, was significantly lower in the DT group than in the D group (24.9 ± 5.9 vs 43.6 ± 12.3 cmH2 O). The inter-contraction interval was significantly longer in the D group than in the ND and DT groups (1566.2 ± 168.7 vs 702.9 ± 165.2 and 787.4 ± 148.8 s). Immunohistochemistry showed positive staining of the urothelial layer for both HIF-1α and 8-OHdG in the D group, but not in the ND or DT groups. Bladder blood flow was significantly lower in the D group than in the ND or DT groups. CONCLUSIONS: Tadalafil improves bladder blood supply and lower urinary tract function in diabetic rats. Tadalafil may be a promising drug that restores lower urinary tract dysfunction in the early phase of diabetes.

Linkage of Lower Urinary Tract Symptoms to Sleep Quality in Elderly Men with Nocturia: A Community Based Study Using Home Measured Electroencephalogram Data.

PURPOSE: We objectively investigated the relationship between sleep quality/efficiency and factors associated with micturition using at-home electroencephalogram assessment. MATERIALS AND METHODS: Participants were recruited from among those enrolled in the Fujiwara-kyo Study, a community based longitudinal evaluation that began in Nara Prefecture, Japan, in 2007. Included participants were men at least 65 years old who woke up in the middle of the night/early morning at least 3 times per week with the urge to void. We evaluated lower urinary tract symptoms using the I-PSS and subjective sleep quality using the Pittsburgh Sleep Quality Index. Uroflowmetry and 3-day frequency volume charting measurements were also obtained. Electroencephalogram recordings were obtained during sleep to evaluate objective sleep quality. RESULTS: Final analysis included data from 47 participants. I-PSS-quality of life score and slow wave sleep time were independent predictors of good subjective sleep quality as determined by Pittsburgh Sleep Quality Index scores. Nocturnal urinary volume was an independent predictor of greater sleep efficiency. Maximum flow rate was an independent predictor of longer slow wave sleep time. CONCLUSIONS: In elderly men with nocturia, sleep quality is associated with lower urinary tract function. Higher subjective sleep quality is associated with longer slow wave sleep time and less severe lower urinary tract symptoms. Higher objective sleep quality is further associated with a higher urinary flow rate and lower nocturnal urinary volume.

Clinical efficacy and safety of mirabegron and imidafenacin in women with overactive bladder: A randomized crossover study (the MICRO study).

AIMS: We aimed to compare the efficacy and safety of mirabegron, a ß3-adrenoceptor agonist, and imidafenacin, an anticholinergic agent, in overactive bladder patients. METHODS: We conducted a multicenter, prospective randomized cross-over study at 5 hospitals in Japan from December 2012 to June 2015. We enrolled female patients with overactive bladder aged ≥50 years, who had never received treatment for the condition. The patients were assigned to Group A or B. Group A patients were administered mirabegron (50 mg per day) for 8 weeks, followed by a 2-week washout period, and then imidafenacin (0.2 mg per day) for 8 weeks. This order of drug administration was reversed in Group B. RESULTS: A total of 33 and 18 patients in Group A and 37 and 26 patients in Group B continued to receive treatment at weeks 8 and 18, respectively. Mirabegron administration significantly improved overactive bladder symptom score (OABSS), the urinary frequency per 24 hr, voided volume per micturition, and number of nocturia episodes per night at week 8. Moreover, imidafenacin administration improved all these variables, except for the number of nocturia episodes per night at week 8. No significant difference was observed in the drug effects between mirabegron and imidafenacin. Although imidafenacin administration significantly increased the scores for dry mouth, blurred vision, and constipation, mirabegron administration did not. CONCLUSIONS: Mirabegron and imidafenacin have the same efficacy. Imidafenacin administration is associated with a higher rate of dry mouth, blurred vision, and constipation as compared to mirabegron administration. Neurourol. Urodynam. 36:1097-1103, 2017. © 2016 Wiley Periodicals, Inc.

[The Influence of Change in Body Water Distribution Caused by Changing Position Upon Nocturia in Older Men].

A total of 29 men 60 years and older (mean age 74 years) who complained at least once about nocturnal voiding and were diagnosed with nocturnal polyuria in the frequency volume chart (FVC) were enrolled in this study. Body water was measured by bioelectric impedance analysis just after lying down at 4 pm and after raising legs 30 minutes later. Nocturnal urine production was measured by FVC, and urine production per unit of time at first nocturnal voiding (urine volume at first nocturnal voiding/hours of undisturbed sleep (HUS) : UFN/HUS), urine production per unit of time during sleep (total nocturnal urine volume/hours of sleep : TNV/HS), etc was evaluated. Extra cellular water (ECW) of 0.19 l (4.0%) in legs was reduced caused by body position changing. There was a significant positive correlation between the amount of ECW in legs and UFN/HUS, TNV/HS (r＝0. 57, p＝0.001 ; r＝0. 38, p＝0.042, respectively). Moreover, UFN/HUS had a significant correlation with soft lean mass in legs, ECW in legs and daytime water intake. This study suggested that a change in leg fluids caused by a change in position results in increased urine production and decreased HUS.

Risk factors of PSA progression and overall survival in patients with localized and locally advanced prostate cancer treated with primary androgen deprivation therapy.

BACKGROUND: Primary androgen deprivation therapy (PADT) has played an important role in the treatment of prostate cancer. We sought to identify factors of PSA progression in our series of patients with localized and locally advanced prostate cancer treated with PADT. METHODS: Six-hundred forty-nine patients with localized and locally advanced prostate cancer who received PADT from 1998 to 2005 by Nara Uro-Oncology Research Group were enrolled. Age, T classification, stage, PSA level at diagnosis, Gleason score, laterality of cancer detected by biopsy and seminal vesicle involvement (SVI) were adopted as parameters of PSA progression. Cox's proportional hazards model was used to determine the predictive factors for PSA progression. RESULTS: The median follow-up period and the median PSA level at diagnosis were 49 months and 15 ng/mL. The 5-year disease specific survival rate, overall survival rate and PSA progression-free survival (PFS) rate were 97.9 %, 91.9 % and 71.2 %, respectively. The univariate analysis showed that the PSA level at diagnosis, Gleason score, laterality of cancer detected by biopsy and SVI were independent predictive parameters of PSA-PFS. However, by multivariate analysis, only laterality of cancer detected by biopsy (unilateral vs. bilateral) was an independent predictive parameter of PSA-PFS (p = 0.034). The patients were classified into new risk groups base on three factors: PSA level at diagnosis, Gleason score, and laterality of cancer detected by biopsy. The PSA-PFS rates at 5-years in the low- (none or one factor), intermediate- (two factors) and high-risk (three factors) groups were 78.2 %, 62.5 % and 46.9 % (p < 0.001), respectively. CONCLUSION: In localized or locally advanced prostate cancer patients who received PADT, laterality of cancer detected by biopsy was a significant predictor associated with a longer PSA-PFS. Our new risk grouping indicates the usefulness of PSA-PFS.

Photodynamic diagnosis of shed prostate cancer cells in voided urine treated with 5-aminolevulinic acid.

BACKGROUND: Past attempts at detecting prostate cancer (PCa) cells in voided urine by traditional cytology have been impeded by undesirably low sensitivities but high specificities. To improve the sensitivities, we evaluate the feasibility and clinical utility of photodynamic diagnosis (PDD) of prostate cancer by using 5-aminolevulinic acid (5-ALA) to examine shed prostate cancer cells in voided urine samples. METHODS: One hundred thirty-eight patients with an abnormal digital rectal exam (DRE) and/or abnormal prostate-specific antigen (PSA) levels were recruited between April 2009 and December 2010. Voided urine specimens were collected before prostate biopsy. Urine specimens were treated with 5-ALA and imaged by fluorescence microscopy and reported as protoporphyrin IX (PPIX) positive (presence of cells demonstrating simultaneous PPIX fluorescence) or PPIX negative (lack of cells demonstrating fluorescence). RESULTS: Of the 138 patients, PCa was detected on needle biopsy in 81 patients (58.7%); of these 81 patients with PCa, 60 were PPIX-positive (sensitivity: 74.1%). Although 57 patients did not harbor PCa by conventional diagnostic procedures, 17 of these at-risk patients were found to be PPIX-positive (specificity: 70.2%). PPIX-PDD was more sensitive compared with DRE and transrectal ultrasound and more specific compared with PSA and PSA density. The incidence of PPIX-PDD positivity did not increase with increasing total PSA levels, tumor stage or Gleason score. CONCLUSIONS: To our knowledge, this is the first successful demonstration of PPIX in urine sediments treated with 5-ALA used to detect PCa in a noninvasive yet highly sensitive manner. However, further studies are warranted to determine the role of PPIX-PPD for PCa detection.

Nadir PSA level and time to nadir PSA are prognostic factors in patients with metastatic prostate cancer.

BACKGROUND: Primary androgen deprivation therapy (PADT) is the most effective systemic therapy for patients with metastatic prostate cancer. Nevertheless, once PSA progression develops, the prognosis is serious and mortal. We sought to identify factors that predicted the prognosis in a series of patients with metastatic prostate cancer. METHODS: Two-hundred eighty-six metastatic prostate cancer patients who received PADT from 1998 to 2005 in Nara Uro-Oncology Research Group were enrolled. The log-rank test and Cox's proportional hazards model were used to determine the predictive factors for prognosis; rate of castration-resistant prostate cancer (CRPC) and overall survival. RESULTS: The median age, follow-up period and PSA level at diagnosis were 73 years, 47 months and 174 ng/mL, respectively. The 5-year overall survival rate was 63.0%. The multivariable analysis showed that Gleason score (Hazard ratio [HR]:1.362; 95% confidence interval [C.I.], 1.023-1.813), nadir PSA (HR:6.332; 95% C.I., 4.006-9.861) and time from PADT to nadir (HR:4.408; 95% C.I., 3.099-6.271) were independent prognostic factors of the incidence of CRPC. The independent parameters in the multivariate analysis that predicted overall survival were nadir PSA (HR:5.221; 95% C.I., 2.757-9.889) and time from PADT to nadir (HR:4.008; 95% C.I., 2.137-7.517). CONCLUSIONS: Nadir PSA and time from PADT to nadir were factors that affect both CRPC and overall survival in a cohort of patients with metastatic prostate cancer. Lower nadir PSA level and longer time from PADT to nadir were good for survival and progression.

Follow-up study of unilateral renal function after nephrectomy assessed by glomerular filtration rate per functional renal volume.

BACKGROUND: To evaluate the clinical usefulness of estimated glomerular filtration rate (eGFR) divided by functional renal volume (FRV) measured by three-dimensional image reconstruction (eGFR/FRV) for the prediction of functional outcomes after nephrectomy. METHODS: Eighty-three patients who underwent nephrectomy were enrolled. The FRV of each patient was measured before surgery. Preoperative medical information on proteinuria, blood pressure, blood glucose level, body mass index (BMI), hemoglobin level and serum cholesterol level were also obtained. We evaluated the relationships between eGFR/FRV and each of these parameters before surgery. We also assessed the potential relationship between eGFR/FRV and the 3-year postoperative eGFR. Stepwise multiple regression analyses were conducted to elucidate independent factors. RESULTS: The median FRV and eGFR were 310.15 cm3 and 79.0 ml/min/1.73 m² before surgery, respectively. The correlation between FRV and eGFR was statistically significant (r = 0.465, P < 0.001). The median eGFR/FRV was 0.24 ml/min/1.73 m²/cm³. Stepwise multiple regression analysis showed that the independent parameters (multiple correlation coefficient, r = 0.389, P = 0.031) associated with eGFR/FRV were proteinuria, BMI, age and hypertension. Proteinuria was statistically associated with eGFR/FRV, and the independent parameters (multiple correlation coefficient, r = 0.694, P < 0.001) associated with the 3-year postoperative eGFR were age, BMI and eGFR/FRV. The eGFR/FRV was statistically associated with the 3-year postoperative eGFR (r = 0.559, P < 0.001). CONCLUSION: The present results demonstrated that patients with proteinuria are expected to have a lower eGFR/FRV than those without proteinuria. The present study also supports the notion that eGFR/FRV is the primary determinant of the long-term functional outcome after nephrectomy. It should be taken into consideration that patients with a low eGFR/FRV may develop chronic kidney disease after nephrectomy.

Guidance on water intake effectively improves urinary frequency in patients with nocturia.

OBJECTIVES: To evaluate how guidance on water-intake impacts the degree of nocturia. METHODS: A total of 67 male patients were enrolled in the present study. Patients were asked to adjust their water and food intakes so that their 24-h urine production/bodyweight would be equal or lower than 30 mL/kg. One month after the treatment, the therapeutic gain from and adverse effects of fluid restriction were examined by comparing the pretreatment and post-treatment value of various parameters. RESULTS: Overall, 65 eligible patients were evaluated. In 44 patients (67%), the frequency of nocturia was improved to one or more times. The change in frequency of nocturia showed a positive correlation with the change in nocturnal urine volume. The change in nocturnal urine volume showed a positive correlation with the changes in 24-h urine production/bodyweight, 24-h drinking volume and daytime drinking volume. The changes in 24-h urine production/bodyweight and daytime drinking volume were independent factors influencing therapeutic effect. None of the participants reported any adverse event. CONCLUSIONS: In patients with a 24-h urine production/bodyweight equal or higher than 30 mL/kg, guidance on water intake might be considered effective and safe as a lifestyle therapy. Water restriction should be carried out not only in the evening, but also during daytime.

[A case of tethered cord syndrome in an elderly man].

A 71-year-old man had been under treatment for nocturia with an anti-cholinergic agent at a urologic clinic for the last 2 years. Because the symptoms did not improve, he was referred to our hospital for treatment of urinary retention. Based on the findings of a neurological examination, we suspected the presence of a neurogenic bladder due to sacral lesions. Moreover, magnetic resonance imaging indicated tethered cord syndrome (TCS) due to spinal cord lipoma. He underwent surgical treatment for TCS, which improved storage function, but not voiding function. Generally speaking, we believe that early diagnosis of TCS facilitates early surgery that can prevent the development of neurogenic disorders. In the present case, if the neurological findings had been appropriately assessed and cystometry/urodynamic studies had been performed at an earlier stage, a prompt diagnosis could have been made and surgery could have been performed earlier as well. Although adult cases with TCS are rarely observed, TCS should be considered as one of the causes of intractable lower urinary tract symptoms.

Impact of Novel Agents on Patient Characteristics, Treatment Patterns, and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer.

BACKGROUND/AIM: The therapeutic landscape for metastatic castration-resistant prostate cancer (mCRPC) has changed dramatically with the introduction of several novel agents. However, limited data are available to determine whether the introduction of novel agents affected patient characteristics, treatment patterns, and outcomes compared with the period when these agents were not available. The objective of this study was to evaluate the impact of the introduction of novel mCRPC agents on patient characteristics, treatment patterns, and outcomes. PATIENTS AND METHODS: Two cohorts of Japanese patients diagnosed with mCRPC between 2009 and 2014 (Epoch 1) and 2015 and 2019 (Epoch 2) were retrospectively analyzed. RESULTS: A total of 125 treatment-naïve mCRPC patients, consisting of 42 patients in Epoch 1 and 83 patients in Epoch 2, were evaluated. We obtained the following results: (i) a dramatic shift in the first-line treatment from docetaxel to androgen receptor axis-targeted agents (ARATs), (ii) an age range expansion for first-line treatment, and (iii) an overall survival (OS) advantage in Eopch 2 compared to Epoch 1. Multivariate analysis in the overall population showed that Epoch 2 and low prostate-specific antigen (PSA) levels at the start of first-line treatment were independent prognostic factors for OS. CONCLUSION: In real-world mCRPC practice, the introduction of novel agents has improved the prognosis of mCRPC while allowing more patients to receive mCRPC treatment across a broad age range. In addition, low PSA levels at the start of first-line treatment were associated with improved OS, indicating the importance of starting mCRPC treatment while PSA levels are low.

Evaluation of factors influencing the natural history of nocturia in elderly subjects: results of the Fujiwara-kyo Study.

PURPOSE: We evaluated the natural history of nocturia and determined factors influencing the incidence or remission of nocturia. MATERIALS AND METHODS: Study subjects were 4,427 volunteers 65 years old or older who participated in the Fujiwara-kyo Study. The nocturia prevalence was assessed at baseline and 1 year later. Nocturia incidence and remission rates were calculated and factors influencing these results were evaluated based on characteristics, including gender, age, body mass index, HbA1c, creatinine clearance, life style, comorbidities, depressive status, metabolic syndrome and voiding symptoms. Independent factors were determined by multivariate analysis. RESULTS: Of the 4,427 subjects 3,685 provided complete replies to self-administered questionnaires at baseline and 1 year later. The prevalence of nocturia at baseline and 1 year later was 47.0% and 50.3%, and nocturia incidence and remission rates were 20.0% and 15.4%, respectively. Male gender, high body mass index, voiding symptom deterioration and new onset overactive bladder were independent factors associated with the nocturia incidence. Male gender, sum of the voiding symptoms, age and new onset overactive bladder were independent negative factors associated with nocturia remission. CONCLUSIONS: The prevalence of nocturia worsened with time, although nocturia in older subjects progressed dynamically. Male gender, age, body mass index, sum of voiding symptoms, voiding symptom deterioration and new onset overactive bladder influence the natural history of nocturia.

Trends of risk classification and primary therapy for Japanese patients with prostate cancer in Nara Uro-Oncological Research Group (NUORG)--a comparison between 2004-2006 and 2007-2009.

BACKGROUND: To assess the trends of risk classification and primary therapy in Japanese patients who were diagnosed with prostate cancer between 2004-2006 and 2007-2009. METHODS: A total of 4752 patients who were newly diagnosed with prostate cancer at Nara Medical University and its 23 affiliated hospitals between 2004 and 2009 were enrolled. The differences in risk classification and primary therapy were compared in patients who were newly diagnosed between 2004-2006 (prior period) and 2007-2009 (latter period). RESULTS: The proportion of patients with a high or greater risk significantly decreased in the latter period compared to the prior period (p < 0.001). The proportion of primary androgen deprivation therapy (PADT) was 50% in the prior period, and 40% in the latter period. On the other hand, the proportion of radiation therapy was 14% in the prior period, but 24% in the latter period. The proportion of radical prostatectomy was the same in the two periods (30%). The primary therapy was significantly different between the two periods (p < 0.001). CONCLUSIONS: Higher risk patients significantly decreased in the latter period compared to the prior period. The use of PADT also significantly decreased in the latter period. However, there were still higher risk patients in Japan, and the use of PADT was still common in patients with localized prostate cancer or locally advanced prostate cancer in Japan.