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Purpose: There is significant lack on evidence regarding the effect of non-adherence to a recommended protocol in follow-up of high-risk non-muscle-invasive bladder cancer (NMIBC), or the impact of delaying detection of recurrent lesion. Here, we aimed to investigate the optimal frequency of follow-up cystoscopy of high-risk NMIBC with respect to oncological safety in the Japanese real-world clinical practice., Methods: This retrospective single-center study included 206 patients with primary high-risk NMIBC. The intensity (%) of follow-up cystoscopy was calculated based on actual visits for cystoscopy and guideline-recommended frequency in the first 24-month follow-up period. Inverse probability of treatment weighting analyses was used to reduce the risk of bias between groups. We performed a restricted cubic spline analysis with knots at intensity of follow-up cystoscopy ≤ 100% group to examine the possible association of progression risk with the intensity of follow-up as a continuous exposure., Results: The median intensity was 87.5% (interquartile range, 75-100). Adjusted multivariate analysis for MIBC-free and progression-free survival demonstrated no significant difference between adjusted ≤ 75% and > 75% intensity groups. A restricted cubic spline analysis suggested no significant effect of the intensity of follow-up on progression risk, and hazard ratios of patients of < 100% intensity were equivalent to those of patients of 100% intensity., Conclusion: Our finding suggested decreased intensity of follow-up cystoscopy did not affect oncological outcomes in patients with high-risk NMIBC. Further prospective trials directly aimed at investigating optimized follow-up schedules for NMIBC are mandatory before substantial changes to existing clinical guidelines., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To evaluate quality of life (QOL) after non-nerve-sparing, robot-assisted radical prostatectomy (RARP) and factors associated with worsened QOL., Methods: Patients who underwent non-nerve-sparing RARP (n = 115) were enrolled. The Expanded Prostate Cancer Index Composite and 8-item Short Form Health Survey were used to evaluate QOL at baseline and postoperative 1, 3, 6, 12, and 24 months. Preoperative factors were evaluated by multivariate analysis for worsened QOL., Results: Postoperative 24-month urinary QOL worsened in 68 of 115 (59%) patients. In multivariate analysis, membranous urethral length ≥10.8 mm [odds ratio (OR): .26, 95% confidence interval (CI): .07-.96] and intravesical prostatic protrusion ≥12 mm (OR: .14, 95% CI .06-.35) were significantly associated with maintaining postoperative 24-month urinary QOL. Significantly more patients with intravesical prostatic protrusion ≥12 mm than < 12 mm had improved urinary QOL. At postoperative 24 months, 43 of 115 (38%) patients had worsened sexual QOL. In multivariate analysis, higher Sexual Health Inventory for Men score (OR: 8.39, 95% CI 2.28-30.9), sexual activity (OR: 6.94, 95% CI: 2.27-21.2), and intercourse activity (OR: 6.81, 95% CI: 1.64-28.3) preoperatively were significantly associated with worsened postoperative 24-month sexual QOL. More patients with high preoperative intercourse activity (12/23,53%) had significantly worsened (p = .009) QOL regarding sexual bother than those who had no preoperative intercourse activity (21/92, 23%)., Conclusion: After non-nerve-sparing RARP, patients with long membranous urethral length and/or intravesical prostatic protrusion maintain urinary QOL. Patients with high intercourse activity presented with impairment of sexual QOL after non-nerve-sparing RARP., (© 2023 John Wiley & Sons Australia, Ltd.)

Objectives: Cryptorchidism (CO) diagnosis by palpation is challenging. Patients with suspected CO are primarily referred to pediatric urologists by general pediatricians and urologists. Currently, surgical treatment for CO is recommended earlier than in previous guidelines. In this study, we evaluated factors that lead to diagnosis discordance and delayed orchidopexy in patients referred with suspected CO in addition to timing of initial screening., Methods: In total, 731 patients (1052 testes) with suspected CO were included. Risk factors for diagnostic discrepancy in CO diagnosis by pediatric urologists and risk of delayed orchiopexy were evaluated., Results: Herein, 659 (90%) patients were diagnosed during routine public health checkups for infants and young children, and 419 (57%) patients were referred by pediatric practitioners. Of 1052 testes, 374 (36%) were diagnosed with CO by pediatric urologists. In multivariate analysis, risk factors of diagnostic discrepancy for CO diagnosis by pediatric urologists were bilateral testis (odds ratio [OR] = 9.17, p < 0.0001), >6 months old at initial diagnosis (OR = 1.036, p < 0.0001), and pediatric referral (OR = 4.60, p < 0.0001). In total, 296 patients underwent orchiopexy for CO. In multivariate analysis, risk factors for delayed orchiopexy were presence of comorbidities (OR = 3.43, p = 0.003) and >10 months old at referral (OR = 12.62, p < 0.0001)., Conclusions: Pediatric referral is a risk factor for discordant CO diagnostics, and late age at referral brings a risk of delayed orchiopexy. It is necessary to enlighten pediatricians, who are mainly responsible for routine health checkups, in teaching CO diagnostic techniques to ensure early referral., (© 2023 The Japanese Urological Association.)

The study aimed to investigate the bladder and urethral activity and nitric oxide (NO)-related molecular changes in aging rats. Rats were divided into two groups: Group Y (young rats; 12 wk) and Group A (aging rats; 15 mo). A 24-h voiding assay was performed, and the urodynamic parameters were evaluated using awake cystometry (CMG) and urethral perfusion pressure (UPP) recordings under urethane anesthesia. The mRNA expression levels of NO-, ischemia-, and inflammation-related markers in urethra and bladder tissues and cGMP levels in the urethra were assessed. Body weight was significantly higher in Group A than in Group Y. Voiding assay results (24 h) were insignificant. In the CMG, the number of non-voiding contractions per voiding cycle and post-void residual volume were significantly higher in Group A than in Group Y; voiding efficiency was significantly lower in Group A than in Group Y. In the UPP recordings, the urethral pressure reduction and high-frequency oscillation (HFO) amplitude were significantly lower in Group A than in Group Y. The mRNA expression levels of Hif-1α, Vegf-a, and Tgf-β1 in the bladder were significantly higher in Group A than in Group Y. The mRNA expression levels of Nos1 and Prkg1 and the cGMP concentrations in the urethra were significantly lower in Group A than in Group Y. Aging rats can be useful models for studying the natural progression of age-related lower urinary tract dysfunctions, for which impaired NO-mediated transmitter function is likely to be an important mechanism. NEW & NOTEWORTHY Aging rats can be useful models for studying the natural progression of age-related lower urinary tract dysfunctions, for which impaired nitric oxide-mediated transmitter function is likely to be an important mechanism.

Background: To investigate the emotional attributes and vaccine implementation rate of patients waiting for kidney transplants during the prolonged COVID-19 pandemic., Methods: We included 145 patients who were on the waiting list at our institution. Clinical information was obtained from medical charts, and emotional changes were assessed using a telephone questionnaire comprising 13 questions, including vaccine implementation. We also investigated factors affecting the decision to accept or decline deceased-donor kidney transplantation during the COVID-19 pandemic., Results: Of the 145 patients, 121 (83.4%) provided informed consent and completed the questionnaire. The median age at registration on the waiting list for deceased-donor kidney transplantation and the median waiting period was 45.5 years and 103 months, respectively. This cohort comprised 84 males and 37 females. Twenty patients (16.5%) were diagnosed with COVID-19, and 15 (12.4%) were more curious about deceased-donor kidney transplantation. One hundred patients (82.6%) were vaccinated against COVID-19 more than thrice. Thirty patients (24.8%) declined, and 91 patients (75.2%) accepted an organ transplant offer during the COVID-19 pandemic. Multivariate analysis revealed that the long-term waiting period (P = .038) and anxiety about COVID-19, such as visiting the transplant facility (P < .0001) and prudence over time (P < .0001), were independent factors influencing the decline of a kidney transplant offer., Conclusions: Our findings suggest that some patients hesitated to undergo deceased-donor kidney transplantation during the pandemic. There is a need to develop an appropriate system to ensure safe and secure kidney transplantation during prolonged pandemics., Competing Interests: Declaration of Competing Interest The study protocol was approved by the Institutional Review Board for Clinical Studies of Nara Medical University (Medical Ethics Committee ID: NMU-2952) and was conducted in compliance with its protocol and the provisions of the 2013 Declaration of Helsinki. Oral informed consent was obtained from all patients on the WL for DDKT, following an explanation of the study objectives and protocol, which was documented in the patients’ medical charts. The datasets generated and/or analyzed during the current study are not publicly available owing to our hospital policy but are available from the corresponding author on reasonable request., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: The stepwise initiation of peritoneal dialysis (PD) using Moncrief and Popovich's technique (SMAP) for catheter insertion is recommended for the systemic introduction of PD and prevention of catheter-related infections. In this study, we investigated patient outcomes in patients who underwent insertion of a PD catheter with a direct method versus the SMAP method., Methods: We enrolled 295 consecutive patients who underwent PD as a primary renal replacement therapy and underwent insertion of a PD catheter at our institute between 2006 and 2021. We retrospectively reviewed their data and investigated patient outcomes, including mortality and PD catheter-related complications., Results: Median age at PD induction was 65 years in the direct insertion group and 65 years in the SMAP group (P = 0.80). The rate of PD introduction after emergency hemodialysis was significantly higher in the direct insertion group than in the SMAP group (P < 0.001). There was no significant difference in survival between the direct insertion and SMAP groups during the median follow-up period of 54 months (P = 0.12). Additionally, patients who transitioned to hemodialysis or kidney transplantation after PD showed significantly longer survival (P < 0.001). The incidence of PD catheter-related complications was not significantly different between the two groups. A body mass index ≥ 23 kg/m 2 was an independent risk factor for peritonitis and exit-site infection (P = 0.006 and P = 0.011, respectively)., Conclusions: Planned sequential renal replacement therapy including hybrid hemodialysis, complete hemodialysis, and kidney transplantation after PD is important for improving patient outcomes. PD catheter insertion by SMAP may not be mandatory in our clinical practice., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Objectives: Diagnosing interstitial cystitis/bladder pain syndrome presents a major challenge because it relies on subjective symptoms and empirical cystoscopic findings. A practical biomarker should discriminate diseases that cause increased urinary frequency, particularly overactive bladder. Therefore, we aimed to identify blood biomarkers that can discriminate between interstitial cystitis/bladder pain syndrome and overactive bladder., Methods: We enrolled patients with Hunner-type interstitial cystitis (n = 20), bladder pain syndrome (n = 20), and overactive bladder (n = 20) and without lower urinary tract symptoms (controls, n = 15) at Ueda Clinic and Nara Medical University Hospital from February 2020 to August 2021. The degree of interstitial cystitis/bladder pain syndrome symptoms was evaluated using the interstitial cystitis symptom and problem indices. Metabolomics analysis was performed on 323 serum metabolites using liquid chromatography time-of-flight mass spectrometry., Results: In the Hunner-type interstitial cystitis or bladder pain syndrome group, we observed smaller relative areas, including anandamide, acylcarnitine (18:2), linoleoyl ethanolamide, and arachidonic acid, compared to those in the overactive bladder or control group. Notably, the differences in the relative areas of anandamide were statistically significant (median: 3.950e-005 and 4.150e-005 vs. 8.300e-005 and 9.800e-005), with an area under the curve of 0.9321, demonstrating its ability to discriminate interstitial cystitis/bladder pain syndrome., Conclusions: Serum anandamide may be a feasible diagnostic biomarker for interstitial cystitis/bladder pain syndrome. Reduced serum anandamide levels may be associated with pain and inflammation initiation, reflecting the pathology of interstitial cystitis/bladder pain syndrome. Furthermore, our findings suggest that abnormal linoleic acid metabolism may be involved in the pathogenesis of interstitial cystitis/bladder pain syndrome., (© 2023 John Wiley & Sons Australia, Ltd.)

Objectives: To verify the effects of penile clamping on the degree of stress urinary incontinence and quality of life in post-radical prostatectomy patients., Results: Thirty-seven patients suffering from stress urinary incontinence after undergoing radical prostatectomy were enrolled. A total of 19 and 18 patients were analyzed in the non-clamp and clamp groups, respectively. The mean ages of the patients in non-clamp and clamp groups were 68.3 ± 7.1 years and 71.2 ± 4.8 years, respectively; the mean time after radical prostatectomy was 28.9 ± 44.0 months and 26.2 ± 39.0 months, respectively. The penile clamp used was the CLAMPMED® (URINE CONTROL CLAMP) size M (MURANAKA MEDICAL INSTRUMENTS Co., Ltd.). Specific urinary care pads (Sawayaka Pad for Men, Small Quantity®, Unicharm Corporation), were provided; the average daily usage was monitored for four weeks. The quality of life was evaluated using the King's Health Questionnaire. The average daily use of urinary care pads was significantly reduced in the clamp group than in the non-clamp group (-0.83 ± 1.51 vs. -0.16 ± 0.69, P = 0.0071). King's Health Questionnaire scores did not change significantly in either group. Wearing the CLAMPMED® reduced the amount of urinary incontinence but did not improve the quality of life., Trial Registration: The Japan Registry of Clinical Trials (jRCT1052230083). Registered 2 August, 2023., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In January 2019, the use of the UroVysion® urine test for surveillance of non-muscle invasive bladder cancer with carcinoma in situ (CIS) was approved in Japan. Clinical evidence of its use remains limited. Herein, we report the real-world clinical practice of the UroVysion test. Of 29 patients underwent at least one UroVysion test at our hospital from 2019 to 2022, only two (6.9%) tested positive without any visible tumor on the cystoscopy after the initial transurethral resection: a 77-year-old man with T1 high-grade tumor and concomitant CIS and a 76-year-old woman with CIS. The remaining 27 patients (93.1%) tested negative post-transurethral resection. This study was the first to report the Japanese real-world practice of the UroVysion test, demonstrating relatively low positive rate as compared to the previous reports from other countries. Further clinical evidence from other Japanese institutes needs to be accumulated to update the true value of this test., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: To compare the perioperative outcomes of patients with complex renal tumors treated with open versus robot-assisted partial nephrectomy., Methods: This retrospective study included 273 patients diagnosed with localized renal tumors at our institution between January 2007 and October 2020. Patients with moderate to high complexity tumors based on the RENAL nephrometry score were included. Perioperative outcomes were compared between open and robot-assisted partial nephrectomy patients. Remnant renal function was defined as the estimated glomerular filtration rate at 12 months after surgery., Results: Open and robot-assisted partial nephrectomy were performed in 43 and 77 patients, respectively. There was no significant difference in overall, cancer-specific, recurrence-free, and metastasis-free survival between the two groups. Remnant renal function was significantly better preserved in the open group, and body mass index was identified as an independent predictive factor (odds ratio 3.05, P = 0.017). Ischemia or type of surgery were not related to remnant renal function. The trifecta achievement rate was 51.2% in the open group and 71.4% in the robot-assisted group (P = 0.031), and the incidence of complications was significantly higher in the open partial nephrectomy group (P = 0.0030). Multivariate analysis revealed that open partial nephrectomy was an independent predictive factor for the incidence of complications (odds ratio 3.92, P = 0.0020)., Conclusion: Robot-assisted partial nephrectomy can provide good and acceptable oncological and functional outcomes with fewer complications in patients with more complex renal tumors. Further research is needed to establish appropriate treatment strategies and guidelines in current clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: Post-evacuation return after mandatory hospital evacuation due to complicated disasters is often overlooked and not well-discussed., Aims: In this study, we explored the factors which are related to the ease or difficulty of the post-evacuation return to Fukushima prefecture of psychiatric inpatients who had been evacuated to hospitals outside the prefecture because of the Great East Japan Earthquake (GEJE) and subsequent Fukushima Daiichi Nuclear Power Plant (FDNPP) accident., Method: This retrospective cohort study included evacuated psychiatric hospital inpatients who were registered in the Matching Project for Community Transition (MPCT) and had been traced until July 31, 2019. A total of 531 patients were included for the analyses. Univariable and multivariable analysis were conducted to detect the patients' traits including their psychiatric/physical backgrounds which were associated with their outcome - the time from GEJE to the date of return to Fukushima., Results: Over half of the patients returned to Fukushima. In the multivariable analysis, the patients' gender (male), age (older), and psychiatric diagnoses of schizophrenia, schizotypal and delusional disorders (ICD-10, F20-29) showed lower hazard ratio (HR) and statistically significant association with the difficulties of post-evacuation return. Meanwhile, disorders of psychological development (F80-89), diseases of the nervous (G00-99, except G40-41) and genitourinary (N00-99) systems showed higher HR and statistically significant association with the ease of return., Conclusions: The specific characteristics of the psychiatric inpatients including their psychiatric and physical status are associated with their post-evacuation return to their hometown. These results indicated that the evacuated hospitals' practitioners and staffs from the MPCT understood the necessity of the earlier return of inpatients to their hometown. Moreover, clinicians should pay more attention to some symptoms unique to psychiatric patients which contributed to their difficulties in returning safely or expressing their hope to return.

Background: To investigate the quality of life (QOL) of patients with nocturia after kidney transplantation (KT) and the association between nocturnal polyuria and sleep quality., Methods: In a cross-sectional study, a patient who consented was evaluated using the following items: international prostate symptom QOL score, nocturia-quality of life score, overactive bladder symptom score, Pittsburgh sleep quality index, bladder diary, uroflowmetry, and bioimpedance analysis. Clinical and laboratory data were obtained from medical charts., Results: Forty-three patients were included in the analysis. Approximately 25% of patients urinated once at night, and 58.1% had nocturia twice. Nocturnal polyuria was observed in 86.0% of patients, and overactive bladder was observed in 23.3% of patients. According to the Pittsburgh sleep quality Index, 34.9% of patients had poor sleep quality. Multivariate analysis revealed that patients with nocturnal polyuria tended to have a high estimated glomerular filtration rate (P = .058). On the other hand, multivariate analysis for poor sleep quality revealed that high body fat percentage and low nocturia-quality of life total score were independently correlated factors (P = .008 and P = .012, respectively). Furthermore, the patients with nocturia ≥3/night were significantly older than those with nocturia ≤2/night (P = .022)., Conclusion: Nocturnal polyuria, poor sleep quality, and aging may decrease the QOL of patients with nocturia after KT. Further investigations, including optimal water intake and interventions, can lead to better management after KT., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The clinical utility of urine nectins in bladder cancer (BCa) is unclear. We investigated the potential diagnostic and prognostic values of urine Nectin-2 and Nectin-4. Levels of urine Nectin-2, Nectin-4, and NMP-22 were quantified using an enzyme-linked immunosorbent assay in 122 patients with BCa, consisting of 78 with non-muscle-invasive BCa (NMIBC) and 44 with muscle-invasive BCa (MIBC), and ten healthy controls. Tumor nectin expression in MIBC was evaluated with immunohistochemical staining of transurethral resection specimens. The level of urine Nectin-4 (mean: 18.3 ng/mL) was much higher than that of urine Nectin-2 (mean: 0.40 ng/mL). The sensitivities of Nectin-2, Nectin-4, NMP-22, and cytology assays were 84%, 98%, 52%, and 47%, respectively; their specificities were 40%, 80%, 100%, and 100%, respectively. Both urine Nectin-2 and Nectin-4, though not NMP-22, were found to be significantly more sensitive than cytology. A four-titer grouping based on levels of urine Nectin-2/Nectin-4 (low/high, high/high, low/low, and high/low) showed a high capability for discriminating between NMIBC and MIBC. Neither urine Nectin-2 nor Nectin-4 levels had a significant prognostic value in NMIBC or MIBC. Urine levels correlated with tumor expression and serum levels in the Nectin-4 analysis, but not in the Nectin-2 analysis. Urine nectins are potential diagnostic biomarkers for BCa.

Background: Photodynamic diagnosis-assisted transurethral resection of bladder tumor reduces the risk of intravesical recurrence compared with conventional white light-transurethral resection of bladder tumor. However, the patient burden of costs for photodynamic diagnosis-transurethral resection of bladder tumor is higher than that for white light-transurethral resection of bladder tumor per installment, and the impact of the medical economics of photodynamic diagnosis-transurethral resection of bladder tumor is unclear. Therefore, we evaluated the Japanese health care system-based cost-effectiveness of photodynamic diagnosis-transurethral resection of bladder tumor compared with that of white light-transurethral resection of bladder tumor., Methods: We conducted a retrospective chart review of 100 patients who underwent initial white light- or photodynamic diagnosis-transurethral resection of bladder tumor for non-muscle invasive bladder cancer from February 2012 to August 2019. Cumulative intravesical recurrences during 1000 post-operative days after the initial transurethral resection of bladder tumor were counted. Furthermore, the cumulative costs were calculated using the Diagnostic Procedure Combination and Per-Diem Payment System unique to Japan. The costs/year/person calculated using the person-year method was compared between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor., Results: Among the 100 patients, 40 (40%) and 60 (60%) underwent the initial white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The cumulative incidence of bladder recurrence requiring hospitalization and transurethral resection of bladder tumor was 20 and 5% for the white light-transurethral resection of bladder tumor and photodynamic diagnosis-transurethral resection of bladder tumor, respectively. The costs for hospitalization and surgical procedures per white light- or photodynamic diagnosis-transurethral resection of bladder tumor were 348 228 and 481 820 Japanese yen, respectively. The cost/year/person by the person-year method was 8073 and 8557 Japanese yen for the white light- and photodynamic diagnosis-transurethral resection of bladder tumor, respectively., Conclusions: The cost/year/person for hospitalization and surgical procedures was slightly different between the white light- and photodynamic diagnosis-transurethral resection of bladder tumor. Furthermore, photodynamic diagnosis-transurethral resection of bladder tumor can reduce intravesical recurrence and is more cost-effective than white light-transurethral resection of bladder tumor., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Recent studies indicate that split renal function calculated by computed tomography (CT) volumetry is equally or more useful than that calculated by nuclear renography for donated kidney side selection. However, it remains unclear if CT volumetry accurately reflects split renal function as measured by nuclear renography. Therefore, this study aimed to evaluate the reproducibility of CT volumetry., Methods: Data from 141 donors who underwent living donor nephrectomy at Nara Medical University from March 2007 to June 2021 were reviewed. The correlation and agreement between the predicted postdonation estimated glomerular filtration rate (eGFR) by 99m Tc-diethylenetriamine penta-acetic acid (DTPA) scintigraphy and by CT volumetry were evaluated by the Pearson's correlation coefficient and Bland-Altman analysis, respectively. Moreover, a comparison in split renal function categorization between 99m Tc-DTPA scan and CT volumetry was performed., Results: A total of 133 donors were included in the analysis. There was high correlation between the predicted postdonation eGFR by 99m Tc-DTPA scintigraphy and by CT. Moreover, there was agreement in the predicted postdonation eGFR between 99m Tc-DTPA scintigraphy and CT volumetry (Bland-Altman analysis [bias, 95% limits of agreement]; 0.83%, -5.6% to 7.3%). However, in one of 17 donors with absolute split renal function greater than 10% by 99m Tc-DTPA scintigraphy, this clinically significant difference was missed by CT volumetry., Conclusion: There are donors for whom a clinically significant split renal function is not accurately reflected in CT volumetry. Future studies need to amend this discrepancy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We aimed to evaluate the effects of a soluble guanylate cyclase (sGC) activator, BAY 60-2770, on neurogenic lower urinary tract dysfunction in mice with spinal cord injury (SCI). Mice were divided into the following three groups: spinal cord intact ( group A ), SCI + vehicle ( group B ), and SCI + BAY 60-2770 ( group C ). SCI mice underwent Th8-Th9 spinal cord transection and treatment with BAY 60-2770 (10 mg/kg/day) once daily for 2-4 wk after SCI. We evaluated urodynamic parameters using awake cystometry and external urethral sphincter electromyograms (EMG); mRNA levels of mechanosensory channels, nitric oxide (NO)-, ischemia-, and inflammation-related markers in L6-S1 dorsal root ganglia, the urethra, and bladder tissues; and protein levels of cGMP in the urethra at 4 wk after SCI. With awake cystometry, nonvoiding contractions, postvoid residual, and bladder capacity were significantly larger in group B than in group C . Voiding efficiency (VE) was significantly higher in group C than in group B . In external urethral sphincter EMGs, the duration of notch-like reductions in intravesical pressure and reduced EMG activity time were significantly longer in group C than in group B . mRNA expression levels of transient receptor potential ankyrin 1, transient receptor potential vanilloid 1, acid-sensing ion channel (ASIC)1, ASIC2, ASIC3, and Piezo2 in the dorsal root ganglia, and hypoxia-inducible factor-1α, VEGF, and transforming growth factor-β1 in the bladder were significantly higher in group B than in groups A and C . mRNA levels of neuronal NO synthase, endothelial NO synthase, and sGCα1 and protein levels of cGMP in the urethra were significantly lower in group B than in groups A and C . sGC modulation might be useful for the treatment of SCI-related neurogenic lower urinary tract dysfunction. NEW & NOTEWORTHY This is the first report to evaluate the effects of a soluble guanylate cyclase activator, BAY 60-2770, on neurogenic lower urinary tract dysfunction in mice with spinal cord injury.

Aims: To examine the circadian expression changes in bladder clock genes in Dahl salt-sensitive rats following high salt intake., Main Methods: Eighteen rats were divided into three groups: the high-salt diet group (HS group), the normal-salt diet group (NS group), and the salt-load interruption group (from a 4 % salt diet to a normal diet; salt-load interruption group [SI group]). Each rat was placed in an individual metabolic cage for 24 h twice weekly. Water intake, urine production, voiding frequency, and voided volume per micturition were recorded. Furthermore, 108 control rats were prepared. Bladders were harvested every 4 h at six time points. Furthermore, the mRNA expression of clock genes and mechanosensors was analyzed., Key Findings: In the HS group, the bladder clock genes showed lower mRNA levels than in the NS group. The amplitude of circadian expression changes in bladder clock genes in the HS group was lower than that in the NS group. However, after changing from a 4 % salt diet to a normal diet, the waveforms of the clock gene expression in the SI group were closer to those of the NS group. The 24-h water intake and urinary volume of the SI group decreased to levels comparable to those of the NS group., Significance: Reduced salt intake partially restored the circadian rhythms of bladder clock genes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy and safety of add-on therapy with the phosphodiesterase type 5 inhibitor tadalafil in Japanese men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with dutasteride., Results: Twenty-four patients were enrolled. The participants had a median age of 71.0 (64.8-73.0) years and a median prostate volume of 37.3 (29.7-41.8) mL as measured using transabdominal sonography. The efficacy indicators, such as International Prostate Symptom Score (IPSS), quality of life (QOL) score, night-time urinary frequency, and night-time maximum voided volume, improved significantly at 4 weeks, and the effects lasted until 24 weeks (IPSS: 9.5 vs. 17.0, QOL: 2.0 vs. 4.0, nocturia: 2.0 vs. 2.0, night-time maximum voided volume: 290.0 vs. 240.0 mL). Overactive bladder symptom score (OABSS) and sexual health inventory for men (SHIM) significantly improved at 12 weeks, and the effects lasted until 24 weeks (OABSS: 3.0 vs. 5.0, SHIM: 11.0 vs. 7.5). However, maximum urine flow and residual urine volume showed no improvement at any point. Adverse events occurred in two cases. Taken together, add-on therapy with tadalafil was effective for patients with LUTS/BPH resistant to dutasteride monotherapy. In addition, this therapy was not associated with severe adverse events., (© 2022. The Author(s).)

Objectives: Diagnosis of Hunner-type interstitial cystitis (HIC) relies on the ability to identify Hunner lesions endoscopically, which can lead to storage symptom misdiagnosis. Here, we examined serum biomarkers for HIC and verified their utility., Methods: Based on the previous definition of the Japanese guidelines, which did not distinguish HIC and non-HIC diseases, we searched for serum biomarkers in 25 patients with interstitial cystitis (IC) and 25 control participants using metabolomics during 2013-2014. In 2019, we conducted a validation study in HIC and control groups. Serum samples were analyzed using liquid chromatography-tandem mass spectrometry, and candidate biomarker concentrations were compared between the groups using Mann-Whitney test., Results: Metabolomics targeted 678 metabolites and revealed that the levels of 14 lysolipids, seven γ-glutamyl amino acids, and two monoacylglycerols were significantly different between the IC and control groups. The following metabolites were selected from each metabolite category as candidates: 1-linoleoylglycerophosphocholine (1-linoleloyl-GPC [18:2]), γ-glutamylisoleucine (γ-Glu-Ile), and 1-arachidonylglycerol (1-AG). The serum concentrations of 1-linoleoyl-GPC (18:2) in the HIC and control groups were 27 920 ± 6261 and 40 360 ± 1514 ng/mL (P = 0.0003), respectively. The serum concentrations of γ-Glu-Ile and 1-AG were not significantly different between the groups. When the cut-off value of 1-linoleoyl-GPC (18:2) was set at 28 400 ng/mL, the sensitivity and specificity were 68% and 84%, respectively., Conclusions: Serum 1-linoleoyl-GPC (18:2) is a candidate diagnostic biomarker for HIC. Additional studies on whether this biomarker can distinguish HIC from other diseases with high urination frequency are required for its clinical use., (© 2022 John Wiley & Sons Australia, Ltd.)

Objectives: To evaluate late genitourinary (GU) and gastrointestinal (GI) toxicities and radiation-induced second primary cancers (RISPCs) in patients who received low-dose-rate brachytherapy (LDR-BT) with or without external beam radiotherapy for prostate cancer., Methods: This retrospective study included 897 consecutive patients who received LDR-BT between July 2004 and July 2015 in our institution. Adverse events and the incidence of second primary cancers were evaluated at 1, 3, 6, 12, 18, 24, 30, 36, 48, 54, and 60 mo after LDR-BT and then once a year. Related factors to ≥grade 2 (G2) toxicity were evaluated using the Cox proportional-hazards model., Results: The median follow-up time was 85.2 (interquartile range: 66.8-111.3) mo. The cumulative incidence rates of ≥G2 GU toxicity at 5 and 10 yrs after LDR-BT were 11.2% and 14.7%, respectively. The International Prostate Symptom Score before LDR-BT (continuous) (hazard ratio [HR]: 1.03), no neoadjuvant androgen deprivation therapy (HR: 1.69), and combination external beam radiotherapy (HR: 3.30) were risk factors related to the incidence of ≥G2 GU toxicity. The cumulative incidence rates of ≥G2 GI toxicity at 5 and 10 yrs after LDR-BT were 3.3% and 3.3%, respectively. Age (continuous) (HR: 1.09), body mass index (continuous) (HR: 0.87), and rectum V100 (continuous) (HR: 1.64) were risk factors related to ≥G2 GI toxicity. A total of 12 (1.3%) patients developed metachronous RISPCs (bladder cancer: 9; rectal cancer: 3)., Conclusion: The incidence rates of late GU and GI toxicities and RISPCs after LDR-BT were low., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

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., (© 2022. The Author(s).)

Purpose: The level of 6-sulfatoxy-melatonin (SaMT), a metabolite of melatonin, in first-void morning urine reflects blood melatonin levels from the previous night. We investigated the association between urine SaMT and sleep quality deterioration in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical Bacillus Calmette-Guerin induction therapy (iBCG)., Methods: We enrolled 51 patients who received iBCG once weekly for 6 or 8 weeks. Patient-reported outcomes were assessed with questionnaires including the International Prostate Symptom Score (IPSS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQC30). Questionnaires were completed before (baseline), during, at completion, and 1 and 3 months after iBCG. Melatonin and SaMT levels at baseline were measured in serum and first-void morning urine samples, respectively., Results: Based on changes in the QLQC30 insomnia subscale, 28 (55%) patients experienced sleep quality deterioration (deterioration group). Urine SaMT values in the deterioration group were lower than those in the non-deterioration group (P = 0.0015; 7.5 vs 15.4 ng/mg creatinine, respectively). Nocturia scores in the non-deterioration group decreased over time, while those of the deterioration group remained high after completion of iBCG. A binary logistic regression analysis revealed that low urine SaMT levels (≤ 9.6 ng/mg creatinine), high IPSS nocturia scores at baseline, and high IPSS storage subscores at baseline were associated with BCG-induced sleep quality deterioration., Conclusions: This study confirmed the association among urine SaMT levels, nocturia, and sleep disturbance in patients with NMIBC who receive iBCG. We should be aware of treatment-induced impairments to aid in appropriate decision-making., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Response to pembrolizumab after first-line chemotherapy is vital to prolonged survival in advanced, unresectable, and/or metastatic urothelial carcinoma (aUC). However, there are sparse clinical data on host-tumor immune modification by first-line platinum-based chemotherapy. This study investigated the association between response to first-line gemcitabine plus cisplatin (GC) or carboplatin (GCarbo) chemotherapy and response to subsequent pembrolizumab treatment., Patients and Methods: A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 108 patients who received first-line GC or GCarbo followed by second-line or later pembrolizumab were eligible for investigation and were classified into 3 groups: 48 receiving full-dose GC, 21 receiving dose-reduced GC, and 39 receiving GCarbo. Overall survival (OS) was calculated using the Kaplan-Meier method and compared using the log-rank test. Possible factors associated with the response to pembrolizumab were evaluated using binary logistic regression methods., Results: The rate of patients undergoing surgical removal of the primary organ was higher and creatinine clearance was lower in the dose-reduced GC and GCarbo groups than in the full-dose GC groups. Pembrolizumab responders had significantly better survival benefits than nonresponders. The rate of pembrolizumab responders was much higher in first-line chemotherapy responders than in first-line chemotherapy nonresponders. In contrast to the full-dose GC and GCarbo groups, the pembrolizumab responder rate was lower, and no association was observed between response to first-line chemotherapy and response to pembrolizumab in the dose-reduced GC group., Conclusion: Cisplatin and carboplatin may play an important role in the antitumor immune response, which could impact the outcome of subsequent pembrolizumab treatment. Given that the rate of response to pembrolizumab after dose-reduced GC chemotherapy was relatively low, this regimen is not recommended for cis-unfit patients with aUC. Further studies are required to understand the mechanisms responsible for the cross-reactivity of platinum and immune checkpoint inhibitors., (Copyright © 2021. Published by Elsevier Inc.)

Background: Latest guidelines recommend kidney-sparing management as the primary treatment option for selected patients with upper urinary tract urothelial carcinoma (UTUC). One of the biggest issues of ureteroscopic laser ablation (ULA) is a high rate of surgical site recurrence, which is largely attributed to residual lesions at the initial ULA. Another clinical issue is a significant lack of non-invasive reliable detection tools of urinary recurrent tumors in this treatment setting., Methods: The FLUAM trial is a prospective, single-center, single-arm pilot trial to investigate the efficacy of 5-aminolevulinic acid-mediated photodynamic diagnosis (ALA-PDD)-assisted ULA for localized UTUC and the usefulness of the UroVysion® assay (multiprobe fluorescence in situ hybridization) as a monitoring test after the kidney-sparing treatment. After the screening and registration, a total of 20 patients with localized UTUC will undergo the initial ALA-PDD-assisted ULA followed by the second look ALA-PDD-assisted ureteroscopic examination. The primary endpoint is progression-free survival. Secondary endpoints include patient reported outcomes, diagnostic accuracy of UroVysion assay to detect tumor recurrence, adverse events, and safety of the intervention., Conclusion: The goal of this trial is to determine the potential benefit of ALA-PDD assistance in patients who undergo the ULA. The evidence of this novel technique is still limited. The results are expected to change the standard of care and lead to better management of localized UTUC., Trial Registration: This clinical trial was prospectively registered with the Japan Registry of Clinical Trials on 23 June 2021. The reference number is jRCTs051210042, nara0023 (Certified Review Board of Nara Medical University)., Competing Interests: M.M., S.H., D.G., Y.N, S.A., K.T., N.T., and K.F. receive 5-aminolevulinic acid hydrochloride from 10.13039/501100002363SBI Pharmaceuticals Co., Ltd. During the conduct of the study. M.M., S.A., K.T., N.T., and K.F. report receiving a joint research fund from SBI Pharmaceuticals Co., Ltd. outside the submitted work (the AMBER study; the Japan Registry of Clinical Trials ID jRCTs051190077). T.Y. received 5-aminolevulinic acid hydrochloride from SBI Pharmaceuticals Co., Ltd. outside the submitted work (the Japan Registry of Clinical Trials ID jRCTs051200004). N.N., Y.O., T.S., N.T., Y.M., and T.F. have no conflict of interest., (© 2022 The Authors.)

Purpose: We investigated sleep parameters and patient-reported outcomes before, during, and after induction Bacillus Calmette-Guerin therapy using questionnaires and actigraphy in patients with non-muscle invasive bladder cancer., Methods: We investigated 10 patients who received Bacillus Calmette-Guerin therapy once weekly for 8 weeks. The International Prostate Symptom Score, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, Functional Assessment of Cancer Therapy-Bladder, and multi-item Short Form-8 tools were used to assess patient-reported outcomes. Participants completed all questionnaires before (baseline), at the 4th and 8th doses, and 1 month after the last Bacillus Calmette-Guerin dose. The MotionWatch8 was fastened to patients' waist throughout the study. Composite sleep quality was determined based on sleep duration, efficiency, and fragmentation., Results: We observed a transient increase in frequency/nocturia subscores and the insomnia subscore. The number of patients with poor sleep quality increased from 0 (0%) at baseline to 7 (70%) at the 4th dose and to 6 (60%) patients at the 8th dose. Among 10 patients, 6 (60%) were assigned to the sleep deterioration group and 4 (40%) to the non-deterioration group. Sleep quality was restored to baseline levels in 5 of 6 patients (83%) within 1 month after the last dose in the sleep deterioration group, and the nocturia subscore of the International Prostate Symptom Score was significantly increased only in this group (P=0.03)., Conclusions: This is the first study that confirms intravesical Bacillus Calmette-Guerin-induced sleep quality deterioration based on a questionnaire survey and actigraphy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To quantify the urinary bladder wall T 1 relaxation time (T 1 ) before and after the instillation contrast mixture in rats previously subjected to water avoidance stress (WAS) and/or acute exposure to protamine sulfate (PS). Female Wistar rats were randomized to receive either sham (control) or 1 h of WAS for ten consecutive days before the evaluation of nocturnal urination pattern in metabolic cages. T 1 mapping of urinary bladder wall at 9.4 T was performed pre- and post- instillation of 4 mM Gadobutrol in a mixture with 5 mM Ferumoxytol. Subsequently, either T 1 mapping was repeated after brief intravesical PS exposure or the animals were sacrificed for histology and analyzing the mucosal levels of mRNA. Compared to the control group, WAS exposure decreased the single void urine volume and shortened the post-contrast T 1 relaxation time of mucosa- used to compute relatively higher ingress of instilled Gadobutrol. Compromised permeability in WAS group was corroborated by the urothelial denudation, edema and ZO-1 downregulation. PS exposure doubled the baseline ingress of Gadobutrol in both groups. These findings confirm that psychological stress compromises the paracellular permeability of bladder mucosa and its non-invasive assay with MRI was validated by PS exposure., (© 2021. The Author(s).)

The debate regarding the need for hospital evacuation and the evacuation distance remains rather chaotic. Furthermore, the relationship between hospital evacuation and the prognoses of psychiatric inpatients has not yet been investigated. We aimed to reveal the association between the long-term prognosis of psychiatric inpatients evacuated immediately following the Fukushima Daiichi Nuclear Power Plant accident and their backgrounds. In this retrospective cohort study, 777 psychiatric inpatients who were immediately evacuated from their hospitals following the accident were included for analysis. Survival time was the primary outcome. We conducted univariable and multivariable analyses to examine the associations between mortality and linear distance of evacuation and different backgrounds, including psychiatric/physical traits. Univariable analysis showed that the estimated survival time among patients was significantly associated with their evacuation distance. A multivariable analysis showed that a longer evacuation distance had a significantly lower hazard ratio (HR) and resulted in lower mortality. In contrast, older patients with physical complications of respiratory disease (International Statistical Classification of Diseases and Related Health Problems 10th revision, J00-99) and genitourinary disease (N00-99) showed a significantly higher HR and had a higher mortality than patients without these complications. To prevent death among elderly psychiatric inpatients with physical comorbidities during disasters, the evacuation destination should be determined taking into consideration the evacuees' tolerance for long-distance transportation and the availability of post-evacuation care in the destination hospitals., (© 2021. The Author(s).)

This study evaluated the time-course changes in bladder and external urinary sphincter (EUS) activity and the expression of mechanosensitive channels in lumbosacral dorsal root ganglia (DRG) after spinal cord injury (SCI). Female C57BL/6N mice in the SCI group underwent transection of the Th8/9 spinal cord. Spinal intact mice and SCI mice at 2, 4, and 6 wk post-SCI were evaluated by single-filling cystometry and EUS-electromyography (EMG). In another set of mice, the bladder and L6-S1 DRG were harvested for protein and mRNA analyses. In SCI mice, nonvoiding contractions were confirmed at 2 wk post-SCI and did not increase over time to 6 wk. In 2-wk SCI mice, EUS-EMG measurements revealed detrusor sphincter dyssynergia, but periodic EMG reductions during bladder contraction were hardly observed. At 4 wk, SCI mice showed increases of EMG activity reduction time with increased voiding efficiency. At 6 wk, SCI mice exhibited a further increase in EMG reduction time. RT-PCR of L6-S1 DRG showed increased mRNA levels of transient receptor potential vanilloid 1 and acid-sensing ion channels (ASIC1-ASIC3) in SCI mice with a decrease of ASIC2 and ASIC3 at 6 wk compared with 4 wk, whereas Piezo2 showed a slow increase at 6 wk. Protein assay showed SCI-induced overexpression of bladder brain-derived neurotrophic factor with a time-dependent decrease post-SCI. These results indicate that detrusor overactivity is established in the early phase, whereas detrusor sphincter dyssynergia is completed later at 4 wk with an improvement at 6 wk post-SCI, and that mechanosensitive channels may be involved in the time-dependent changes. NEW & NOTEWORTHY This is the first paper to evaluate the time-course changes of bladder dysfunction associated with mechanosensitive channels in a mouse model.

We treated a man with a chief complaint of memory impairment after the Great East Japan Earthquake. Initially, he was diagnosed with dementia. However, after several tests, neither could a definitive diagnosis of dementia be reached, nor was there any apparent evidence for depression, epilepsy, delirium, or internal medicine diseases. During the earthquake, the patient experienced the severe trauma of watching his wife being swept away by a tsunami. Furthermore, he experienced separation from his family. Because of this traumatic experience, we suspected that dissociative disorder was involved in the development of the memory impairment and thus, we switched to treatments focusing on emotional support. Subsequently, the patient's memory impairment gradually improved. The present case demonstrates the importance of considering dissociative disorders when examining a patient with memory impairment in areas affected by disasters.

Background: A history of preoperative obstructive pyelonephritis has been reported as a risk factor for febrile urinary tract infection (fUTI) after ureteroscopic lithotripsy (URSL). But there is no clear evidence of risk factors for developing fUTI including the optimal timing of URSL after obstructive pyelonephritis treatment., Methods: Of the 1361 patients, who underwent URSL at our hospital from January 2011 to December 2017, 239 patients had a history of pre-URSL obstructive pyelonephritis. The risk factors were analyzed by comparing the patients' backgrounds with the presence or absence of fUTI after URSL. The factors examined were age, gender, body mass index, comorbidity, presence or absence of preoperative ureteral stent, stone position, stone laterality, stone size, Hounsfield unit (HU) value on computed tomography scan, history of sepsis during obstructive pyelonephritis, period from antipyresis to URSL, ureteral stenting period, operation time, and presence or absence of access sheath at URSL. In addition, the stone components and renal pelvic urinary culture bacterial species during pre-URSL pyelonephritis were also examined., Results: Post-URSL fUTI developed in 32 of 239 patients (13.4%), and 11 of these 32 cases led to sepsis (34.4%). Univariate analysis showed that stone position, stone maximum HU value, presence of sepsis during obstructive pyelonephritis, period from antipyresis to URSL, pre-URSL ureteral stent placement, operation time were risk factors of fUTI. Stone components and urinary cultures during pyelonephritis were not associated with risk of fUTI. Multivariate analysis showed that renal stone position, pre-URSL ureteral stent placement > 21 days, and operation time > 75 min were independent risk factors of fUTI following the URSL., Conclusions: F-UTI following the URSL could be avoided by ureteral stent placement period 21 days or less and operation time 75 min or less in patients with obstructive pyelonephritis.

Background: Selecting the treatment procedure for cancer patients is a challenging task. We report our initial experience of complete laparoscopic radical nephroureterectomy (RNU) for patients with upper urinary tract urothelial cancer (UTUC)., Methods: A total of four patients with UTUC underwent complete laparoscopic RNU combined with transvesical laparoscopic excision of the distal ureter using three 5-mm ports. Transvaginal specimen extraction was applied in female patients to reduce incisional pain and improve cosmesis. Peri-operative complications were evaluated using the Clavien-Dindo classification system. Postoperative pain was evaluated during hospitalization using a numeric pain rating scale (scales of 1 to 10). Patients who underwent retroperitoneal laparoscopic surgery combined with open excision of the distal ureter during the same period were included as a control group (conventional RNU, consisting of laparoscopic nephrectomy combined with open bladder cuff excision) for pain scale evaluation., Results: The novel surgery was successfully completed for all four patients (two males and two females). The mean pneumoperitoneum time for retroperitoneoscopic nephroureterectomy and specimen extraction was 174 min, while the mean pneumovesicum time for the ureteral orifice excision was 88 min. One male patient had bladder leakage at the suture site of the bladder wall, which lasted for 2 weeks. No patient experienced recurrent disease during the follow-up period (median, 10 months). Mild to moderate pain lasted for 5 or 6 days after RNU. A couple of days after surgery, the numeric pain rating scale of complete laparoscopic RNU and conventional RNU group reached its peak level at 3.0 ± 1.8 and 5.3 ± 2.8, respectively. There was no statistical difference in the degree of postoperative pain (P = 0.31)., Conclusions: We described our initial experience and outcome of complete laparoscopic RNU for UTUC. Further experience and research are required to determine whether this advanced laparoscopic technique yields better outcomes and has true clinical value.

Aims: To establish an animal model of diabetes mellitus (DM) with moderately elevated blood glucose levels, and to examine the nitric oxide (NO) mechanism controlling urethral function in streptozotocin (STZ)-induced DM rats., Main Methods: Female Sprague-Dawley rats were used. DM was induced by intraperitoneal injection of STZ (65 mg/kg) and some of them received subcutaneous implantation of a low-dose insulin pellet. Voiding behavior was evaluated in metabolic cages. Isovolumetric cystometry and urethral perfusion pressure (UPP) were then evaluated under urethane anesthesia, during which L-arginine (100 mg/kg) and N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (50 mg/kg) were administered intravenously. In vitro urethral activity was also tested by organ bath muscle strip studies., Key Findings: UPP changes and high-frequency oscillation (HFO) were significantly (P < 0.05) smaller in 8-weeks DM rats vs. normal control (NC) rats or insulin-treated DM rats, which showed reductions in urine overproduction and voided volume per micturition vs. untreated DM rats. UPP nadir was decreased by L-arginine in NC and insulin-treated DM groups, and decreased by L-NAME in all groups. Five of 6 untreated DM rats showed a detrusor-sphincter dyssynergia pattern after L-NAME. In in vitro studies, the relative ratio of L-NAME-induced reductions of urethral relaxation against pre-drug urethral relaxation was significantly smaller in DM vs. NC rats (P < 0.05)., Significance: Low-dose insulin-treated DM rats would be a useful model for studying natural progression of DM-induced lower urinary tract dysfunction. The impaired NO-mediated urethral relaxation mechanisms play an important role in DM-induced urethral dysfunction, which could contribute to DM-induced inefficient voiding., Competing Interests: Declaration of competing interest There is no potential conflict of interest relevant to this article among authors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease (AD) is a chronic, progressive disorder that causes declines in cognitive and physical functions. This condition places severe burdens on families and caregivers. Delaying progressive declines in cognitive function and reducing their burden are thus important. Relationships between early treatment response and subsequent outcomes of schizophrenia and major depressive disorder have been reported. We thus aimed to investigate the relationships between treatment response to antidementia drugs in AD after 6 months (M) and subsequent outcomes., Methods: Eligible individuals comprised 194 patients diagnosed with presumed AD. Of these, 110 patients who received antidementia drugs for the first time and were assessed using the Mini-Mental State Examination (MMSE) at 6 M, 12 M, and 24 M were categorized as responders (n = 84) or nonresponders (n = 26). Responders were defined as showing a change in MMSE after 6 M the same as or lower than that in the natural course according to previously reported data., Results: No significant differences in baseline characteristics (age, sex, education, or comorbidities) were seen between groups. Mean MMSE score at baseline was significantly lower in responders (18.0) than in nonresponders (20.7; P = 0.008). Mean change from baseline MMSE was significantly smaller in responders than in nonresponders at both 12 M (-0.46 vs -2.5; P = 0.04) and 24 M (-0.78 vs -4.4; P = 0.001)., Conclusions: Treatment response with antidementia drugs after 6 M predicted better outcomes at 12 M and 24 M. Treatment response should be assessed every 6 M, and treatment should be reconsidered accordingly.

Prostate inflammation (PI) is a clinical condition associated with infection and/or inflammation of the prostate. It is a common disease frequently associated to lower urinary tract (LUT) symptoms. The urethra is an understudied structure in the LUT and plays a fundamental role in the urinary cycle. Here, we proposed to evaluate the effect of PI on the urethra tissue. Male Sprague-Dawley rats were used, and PI was induced by formalin injection into the ventral lobes of the prostate. The pelvic urethra at the prostatic level was harvested for histological analysis, contraction (electrical field stimulation and phenylephrine), and relaxation (sodium nitroprusside/MK-571) experiments. Various gene targets [cytochrome c oxidase subunit 2, transforming growth factor-β 1 , interleukin-1β, hypoxia-inducible factor-1α, α 1A -adrenoceptor, inositol 1,4,5-trisphosphate receptor type 1, voltage-gated Ca 2+ channel subunit-α 1D , neuronal nitric oxide synthase, soluble guanylyl cyclase, phosphodiesterase 5A, protein kinase CGMP-dependent 1, and multidrug resistance-associated protein 5 (MRP5; ATP-binding cassette subfamily C member 5)] were quantified, and cGMP levels were measured. No histological changes were detected, and functional assays revealed decreased contraction and increased relaxation of urethras from the PI group. The addition of MK-571 to functional assays increased urethral relaxation. Genes associated with inflammation were upregulated in urethras from the PI group, such as cytochrome oxidase c subunit 2, transforming growth factor-β 1 , interleukin-1β, and hypoxia-inducible factor-1α. We also found increased expression of L-type Ca 2+ channels and the neuronal nitric oxide synthase enzyme and decreased expression of the MRP5 pump. Finally, cGMP production was enhanced in urethral tissue of PI animals. The results indicate that PI is associated with proinflammatory gene expression in the urethra without histologically evident inflammation and that PI produces a dysfunctional urethra and MRP5 pump downregulation, which results in cGMP accumulation inside the cell. These findings would help to better understand LUT dysfunctions associated with PI and the role of MRP pumps in the control of LUT function.

Objective: This study investigated the effects of tadalafil on the urethra and detrusor in the initial phase of diabetes in rats., Methods: Thirty-six female Sprague-Dawley rats were assigned to a non-diabetes (ND), diabetes (D), or tadalafil-treated diabetes (DT) group (n = 12 per group), with the DT group receiving oral tadalafil (2 mg/kg/d) for 7 days before the experiments. Seven weeks after diabetes induction (by a single intraperitoneal injection of streptozotocin), urethral and intravesical pressure were simultaneously recorded in vivo, whereas responses of detrusor strips to potassium chloride (30 mM), electrical field stimulation (EFS) and carbachol were measured in vitro., Results: The intravesical pressure at which the urethra started to relax was significantly lower in the DT than D group (mean [± s.d.] 18.9 ± 2.9 vs 29.1 ± 6.6 cm H 2 O; P < .05). In addition, the reduction in urethral pressure was significantly larger in the DT than D group (-10.9 ± 4.0 vs -4.0 ± 2.9 cm H 2 O; P < .05). Detrusor stimulation revealed that the mean contractile responses to EFS and carbachol were significantly lower in the ND and DT groups than in the D group (120.7 ± 26.5% and 130.8 ± 15.8% vs 200.1 ± 47.9% of the 30 mM KCl-induced contraction, respectively, in response to 50 Hz EFS [P < .05]; 211.1 ± 35.4% and 208.4 ± 25.3% vs 425.7 ± 125.0% of the 30 mM KCl-induced contraction, respectively, in response to 10 -3 M carbachol [P < .05])., Conclusions: Tadalafil restored urethral relaxation function and detrusor responses to EFS and carbachol during the initial phase of diabetes., (© 2019 John Wiley & Sons Australia, Ltd.)

Purpose: To assess the long-term changes in renal function, blood electrolyte levels, and nutritional indices after radical cystectomy and ileal conduit in patients with bladder cancer., Patients and Methods: In 129 patients who underwent radical cystectomy and ileal conduit, we evaluated clinicopathologic features, complications, and the change in the estimated glomerular filtration rate (eGFR) from baseline to 1, 2, 3, 4, 5, and 10 years postoperatively. Two nutritional indices, the geriatric nutritional risk index (GNRI) and prognostic nutrition index (PNI), were calculated with laboratory tests. The Student t-test, Mann-Whitney U test, paired t-test, or Wilcoxon's signed-rank test was used, as appropriate., Results: In the ileal conduit group, a parastromal hernia was observed in 10% of patients, whereas 13% had an ureteroenteric anastomotic stricture, which was associated with greater decline in the eGFR postoperatively. The first 5 year-decline in the eGFR was 1.74 mL/min/1.73 m2/year. The levels of only potassium showed a significant increase at 1 year postoperatively (mean: 4.34 mEq/L) and remained high compared with the baseline (4.14). Evaluation of the nutritional indices demonstrated that the GNRI, not PNI, showed a significant, transient increase from 1 to 4 years (range: 108?110) postoperatively compared with the baseline (105)., Conclusion: The first 5 year-decline was much higher than that among Japanese individuals who participated in an annual health examination program. Further research should be performed to identify an appropriate strategy for selecting the suitable type of urinary diversion and postoperative nutritional interventions to improve the clinical outcome of patients with bladder cancer.

Background: Retroperitoneal tumors are an uncommon disease known to consist of a diverse group of benign and malignant neoplasms. Treatment of unresectable retroperitoneal lesions requires pathological diagnosis. Here, we report the utility and safety of retroperitoneoscopic biopsy for unresectable retroperitoneal lesions excluding urogenital cancers., Methods: We analyzed 47 patients consisting of 23 (49%) and 24 (51%) cases that underwent retroperitoneoscopic tissue biopsy and open biopsy, respectively. The clinicopathological features, including postoperative complications, were compared between the two groups., Results: Tumor pathology was diagnosed successfully with a single operation in all patients. Malignant pathology (68%) was more common than benign pathology (32%). The most common pathology was malignant lymphoma, which accounted for about 50% of all cases. There was no significant difference with respect to the age, sex, tumor size, presence of tumor-related symptom, histopathology, operative time, and complications. Three (13%) of 23 patients in the retroperitoneoscopic biopsy group received percutaneous needle biopsy before laparoscopic excisional biopsy because the evaluation of needle cores failed to confirm subclasses of diagnosed pathologies. One patient was converted to open surgery just after the initiation of operation due to severe adhesion of adjacent structures. We had two cases with iatrogenic urinoma due to ureteral injury after retroperitoneoscopic biopsy., Conclusions: We conclude that retroperitoneoscopic biopsy is a safe and useful tool for benign and malignant retroperitoneal lesions, in comparison to open biopsy. It is critical to carefully examine the preoperative imaging for the location of tumors, especially those close to the renal pelvis and ureter.

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 cmH 2 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., (© 2017 Wiley Periodicals, Inc.)