Optogenetic stimulation of neurons in the anterior cingulate cortex induces changes in intravesical bladder pressure and the micturition reflex.

Lower urinary tract (LUT) function is controlled by the central nervous system, including higher-order cognitive brain regions. The anterior cingulate cortex (ACC) is one of these regions, but the role of its activity in LUT function remains poorly understood. In the present study, we conducted optogenetic experiments to manipulate neural activity in mouse ACC while monitoring bladder pressure to elucidate how the activity of ACC regulates LUT function. Selective optogenetic stimulation of excitatory neurons in ACC induced a sharp increase in bladder pressure, whereas activation of inhibitory neurons in ACC prolonged the interval between bladder contractions. Pharmacological manipulation of ACC also altered bladder contractions, consistent with those observed in optogenetic experiments. Optogenetic mapping of the cortical area responsible for eliciting the increase in bladder pressure revealed that stimulation to ACC showed more potent effects than the neighboring motor cortical areas. These results suggest that ACC plays a crucial role in initiating the bladder pressure change and the micturition reflex. Thus, the balance between excitation and inhibition in ACC may regulate the reflex bidirectionally.

Acquired Cystic Disease-Associated Renal Cell Carcinoma: A Systematic Review and Meta-analysis.

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a common subtype of renal cell carcinoma (RCC) in end-stage renal disease (ESRD) patients. The current systematic review and meta-analysis was performed to evaluate the clinicopathological, and genetic characteristics of patients with ACD-RCC. A systematic search on three electronic databases including the Pubmed, Scopus, and Web of Science databases were performed until December 31, 2022. A meta-analysis was performed following the PRISMA 2020 Guidelines. Of 888 identified articles, full-text screening in 69 articles, there were 26 articles analyzed, with a total of 2314 tumors in 2199 patients, including 418 ACD-RCC tumors in 363 patients, 1340 clear cell RCC (ccRCC) tumors, 308 papillary RCC (pRCC) tumors. Most ACD-RCC patients were male (80.2%). All the ACD-RCC patients underwent prior dialysis with 148.2 months of mean dialysis duration. There were 8.7%, 3.4%, and 5.8% tumors at the T3-4 stage, N1 stage, and M1 stage, respectively. The mean overall survival of ACD-RCC patients was 39.6 months (95% CI, 26.6-52.5). Compared to ccRCC and pRCC, ACD-RCC patients had a longer duration of dialysis (MD: 103.5 and 31.77 months, respectively; 95% CI: [75.48; 131.53] and [0.95; 62.58], respectively), and a higher rate of multifocal tumors (MD: 3.46 and 2.45 tumors, respectively; 95% CI [1.71; 6.98] and [1.26; 4.79], respectively). Regarding genetic characteristics, chromosomes 3 and 16 were the 2 most frequent chromosomal aberrations. The missense mutation in KMT2C (25%) and TSC2 (18.75%) were the 2 most common gene mutations in ACD-RCC. In conclusion, the ACD-RCC subtype exhibited several distinct clinicopathological and genetic characteristics compared to others RCC subtypes. Further researchs are needed to assess the survival outcome and the genetic characteristics of this subtype.

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

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

Robot-assisted radical nephroureterectomy for right renal pelvic tumor post sacrocolpopexy with mesh: A case report.

INTRODUCTION: Robot-assisted nephroureterectomy for upper tract urothelial carcinoma has been increasingly performed as a minimally invasive procedure recently. However, there are concerns regarding its adoption in highly complex cases with dense adhesions. PRESENTATION OF CASE: An 86-year-old woman presented to our hospital with gross hematuria one year after having undergone robot-assisted sacrocolpopexy using a mesh for pelvic organ prolapse. Cystoscopy revealed hematuria from the right ureteral orifice. Computed tomography suggested right hydronephrosis; retrograde pyelography showed a defect in the right renal pelvis with class V urine cytology of the urine from the right kidney. Based on these findings, a right renal pelvic tumor was diagnosed, and robot-assisted nephroureterectomy was performed. The patient was discharged on postoperative day 7 without complications. DISCUSSION: To the best of our knowledge, this is the first case report in which robot-assisted radical nephroureterectomy was performed after robot-assisted sacrocolpopexy with a mesh. Dense tissue adhesions are encountered not only between the bladder and the anterior vaginal wall but also around the right ureter in the pelvis. In this case, dense adhesions were confirmed around the right ureter in the pelvis. CONCLUSION: Robot-assisted nephroureterectomy may be considered an option for minimally invasive surgery in cases with a history of pelvic organ prolapse surgery using mesh.

NAA10 gene expression is associated with mesenchymal transition, dedifferentiation, and progression of clear cell renal cell carcinoma.

INTRODUCTION: We aimed to investigate the expression and prognostic role of NAA10 in clear cell renal cell carcinoma (ccRCC). MATERIAL AND METHODS: We performed a gene expression and survival analysis based on the human cancer genome atlas database of ccRCC patients (TCGA-KIRC). RESULTS: The patients in the TCGA-KIRC (n = 537) were divided into two subgroups: NAA10-low and NAA10-high expression groups. NAA10-high ccRCC exhibited higher T stages (p = 0.002), a higher frequency of distant metastasis (p = 0.018), more advanced AJCC stages (p < 0.001), a lower overall survival time (p = 0.036), and a lower survival rate (p < 0.001). NAA10-high ccRCC was associated with increased activity of non-specific oncogenic pathways, including oxidative phosphorylation (p < 0.001) and cell cycle progression [G2 to M phase transition (p = 0.045) and E2F targets (p < 0.001)]. Additionally, the NAA10-high tumors showed reduced apoptosis via TRIAL pathways (p < 0.001) and increased levels of activity that promoted epithelial-mesenchymal transition (p = 0.026) or undifferentiation (p = 0.01). In ccRCC, NAA10 expression was found to be a negative prognostic factor in both non-metastatic (p < 0.001) and metastatic tumors (p = 0.032). CONCLUSIONS: In ccRCC, NAA10 expression was shown to be a negative prognostic factor related to tumor progression rather than tumor initiation, and high NAA10 expression promoted epithelial-mesenchymal transition and undifferentiation.

Hypopituitarism induced by pembrolizumab plus axitinib in the treatment of metastatic renal cell carcinoma: A case report.

Immune checkpoint inhibitor (ICI) therapies have broadened the armamentarium for metastatic renal cell carcinoma (mRCC). As the ICI therapy spreads in the clinical settings, immune-related adverse events are more of a concern for clinicians. The present study reports three cases of mRCC treated with pembrolizumab plus axitinib and diagnosed hypopituitarism based on clinical symptoms and hormonal profile. Acute methylprednisolone infusion therapy was necessary in one case because of severe adrenal hypofunction; however, the clinical symptoms of the other two cases were controlled with oral corticosteroid therapy. To the best of our knowledge, there is no report of pembrolizumab plus axitinib related hypopituitarism in the treatment of mRCC. The present cases suggests that hypopituitarism after pembrolizumab plus axitinib treatment for mRCC can be handled with steroid therapy even after the development of hypopituitarism.

Scrotal epidermoid cysts penetrating the penile corpora cavernosa: Two case reports.

Introduction: Epidermoid cysts are tumors and that rarely occur in intrascrotal extratesticular tissues. It is extremely rare for the tumors to penetrate the penile corpora cavernosa. Case presentation: We encountered a 4-year-old and a 6-year-old boy with intrascrotal tumors that penetrated the penile corpora cavernosa. Both the patients underwent tumor resection. In the former case, some of the tumor within the corpora cavernosa was left behind, while in the latter case, the tumor was completely resected. Pathological examination in both cases confirmed the diagnosis of epidermoid cysts. Conclusion: We should consider the possibility of epidermoid cysts in children presenting with intrascrotal tumors. Moreover, care should be taken when handling the corpora cavernosa during surgery.

The prevalence and predictive factors of nocturnal polyuria in Japanese patients with nocturia: a multicentral retrospective cohort study.

The aims of this study were to determine the prevalence and predictors of nocturnal polyuria (NP) in Japanese patients. This multicentral, observational study enrolled patients with the chief complaint of nocturia at 17 Japanese institutions between January 2018 and December 2022. The frequency of daily voiding and volume of urination were evaluated using bladder diaries. NP was diagnosed in patients with an NP index of > 33%. The primary endpoint was NP prevalence in patients with nocturia. The secondary endpoints were the prevalence of NP according to sex and age and the identification of factors predicting NP. This study analyzed 875 eligible patients. NP was present in 590 (67.4%) patients, with prevalence rates of 66.6% and 70.0% in men and women, respectively. Age ≥ 78 years, body mass index (BMI) < 23.0 kg/m2, and patients with ischemic heart or cerebrovascular disease were significant predictors of NP (P < 0.001, P < 0.001, P = 0.014, P = 0.016, respectively). This is the first large multicenter study to investigate the prevalence of NP in Japanese patients with nocturia. NP has a prevalence of 67.4%. Significant predictors of NP include age, BMI, and cardiovascular disease.

Importance of Regular Examination and Follow-up in Pediatric Patients with Neurogenic Bladder: 24-Month Follow-up Study Using a Japanese Health Insurance Database.

INTRODUCTION: Data on the long-term management of neurogenic bladder (NGB) are scarce. We evaluated the current status of NGB management in Japanese children over 24-month follow-up using the JMDC database. METHODS: In this descriptive, observational, retrospective cohort study, patients (≤ 17 years) with NGB were included. Patient characteristics and their management status were investigated. A multivariate analysis evaluating the potential risk factors for the development of urinary tract infection (UTI) was performed. The diagnosis of spina bifida, demographics, baseline comorbidities, and early use of clean intermittent catheterization (CIC) and/or overactive bladder (OAB) drugs were used as independent variables. RESULTS: Of 883 eligible children, 39.3% had spina bifida. Over 12/24-month post-index periods, renal urinary tract ultrasound and urinalysis were performed at least once in > 35%/> 45% patients, respectively, while specific tests (urodynamics, cystourethrography, scintigraphy) were performed in substantially fewer (< 11%/< 13%) patients. Over 24 months, 21.5% patients used OAB medications (mostly anticholinergics) and 10.8% underwent CIC, alone or with medications; 1.2% patients underwent surgery. Lower UTI (23.3%), urinary incontinence (9.7%), and hydronephrosis (7.0%) were the most common incident complications. Multivariate analysis evaluating risk factors for UTI showed significantly higher odds ratios with point estimates of ≥ 2 for CIC (5.70), presence of spina bifida (2.86), and constipation (2.07). Overall, urodynamic assessments were inadequately performed. CONCLUSION: Patients with use of CIC and/or having spina bifida and constipation had a higher risk of UTI, suggesting the need for careful follow-up. More guideline-compliant and diligent patient management is necessary in Japanese children with NGB.

G protein-coupled receptor 55 activated by palmitoylethanolamide is associated with the development of nocturia associated with circadian rhythm disorders.

AIMS: Bladder function is regulated by clock genes and dysregulation of circadian bladder function can cause nocturia. The blood concentration of palmitoylethanolamide (PEA), a fatty acid metabolite, changes with circadian rhythm. Clock gene abnormalities demonstrate the highest PEA levels during the sleep phase. PEA is a GPR55 agonist that influences urination; therefore, increased PEA during the sleep phase may cause nocturia. Herein, we investigated the function of GPR55 to evaluate the relationship between GPR55 and nocturia that evoked higher PEA during the sleep phase in patients with circadian rhythm disorders. MAIN METHODS: Male C57BL/6 mice were used. GPR55 localization was evaluated by immunofluorescence staining, qRT-PCR, and western blotting. Variations in PEA-induced intracellular Ca2+ concentrations were measured in primary cultured mouse urothelial cells (UCs) using Ca2+ imaging. PEA-induced NGF and PGI2 release in UCs was measured by ELISA. The micturition reflex pathway after PEA administration was evaluated using immunofluorescence staining. KEY FINDINGS: GPR55 was predominant in the UC layer. PEA induced release of Ca2+ from the endoplasmic reticulum into the UC cytoplasm. ELISA and immunofluorescence staining revealed that NGF and PGI2 were released from bladder UCs, stimulated the pontine micturition center in mice, and induced nocturia. SIGNIFICANCE: The loss of regular circadian metabolizing rhythm in fatty acids causes higher blood PEA levels during the sleep phase. Binding of PEA to GPR55 in UC may activate the downstream processes of the micturition reflex, leading to nocturia. These findings suggest a new mechanism for nocturia and its potential as a therapeutic target.

A case of proximal migration of a double-J ureteral stent in a patient with metastatic gastric cancer.

Ureteral stenting is a common procedure to relieve ureteral obstructions. There are few reports regarding the proper migration of the proximal coil of a double-J ureteral stent into the ureter. Herein, we report a case of proximal stent migration after stent placement for ureteral stenosis caused by a malignant tumor in the gastrointestinal tract.

Hygiene management of intermittent self-catheterization using reusable silicone catheters in people with spinal cord lesions: A cross-sectional Internet survey in Japan.

OBJECTIVES: To investigate hygiene management and catheter maintenance of reusable silicone catheters for intermittent self-catheterization (ISC) in Japan and examine their relationship with symptomatic urinary tract infection (sUTI). METHODS: We conducted a cross-sectional Internet survey of people performing ISC using reusable silicone catheters owing to spinal cord lesions in Japan. Hygiene management and catheter maintenance of reusable silicone catheters and the incidence and frequency of sUTI were evaluated. We also examined the significant risk factors for sUTI. RESULTS: Of 136 respondents, 62 (46%), 41 (30%), and 58 (43%) washed hands with water, washed hands with soap, and cleaned or disinfected the urethral meatus every time or most of the time before ISC, respectively. No significant difference was observed in the incidence and frequency of sUTI between respondents who adhered to these procedures and those who did not. There were no significant differences in the incidence and frequency of sUTI in respondents who changed their catheters every month and in those who changed their preservation solution within 2 days compared with those who did not. In multivariate analysis, pain during ISC, inconvenience of indoor mobility, bowel management problems, and participants' feeling of never having received instruction on catheter replacement were significant risk factors for sUTI. CONCLUSIONS: There are individual differences in hygiene management and catheter maintenance of reusable silicone catheters, but the influence of these differences on the incidence and frequency of sUTI is not clear. Pain during ISC, bowel management problems, and inadequate instruction on catheter maintenance procedures are factors associated with sUTI.

Metastatic rectal neuroendocrine tumor to kidney, pancreas, and bone following renal tumor resected with robot-assisted laparoscopic partial nephrectomy.

Neuroendocrine tumor (NET) is a rare tumor commonly found in the gastrointestinal tract and lungs and rarely originates from and metastasizes to the kidney. We report a case of a 66-year-old man with metastatic rectal NET to the kidney, pancreas and bone following the resection of renal tumor with robot-assisted partial nephrectomy (RAPN). A rectal tumor of 10mm in diameter had been endoscopically resected and diagnosed NET with positive surgical margin 9 years before RAPN. Somatostatin receptor (SSR) scintigraphy revealed the other two metastases postoperatively, therefore is an effective tool to detect primary and metastatic sites of NETs.

Diagnosis and Treatment of Japanese Children with Neurogenic Bladder: Analysis of Data from a National Health Insurance Database.

In pediatric patients with neurogenic bladder (NGB), urinary tract evaluation, early diagnosis, and individualized management are important. We aimed to clarify the current status of diagnosis and treatment of NGB in Japanese children. This descriptive, observational, retrospective cohort study using the JMDC claims database included NGB patients aged ≤17 years over a 12-month follow-up period. Of the 1065 pediatric NGB patients, 38.9% had spina bifida. Dermatological and gastrointestinal comorbidities were common in the baseline period. Renal/bladder ultrasound was a commonly performed investigation (38.3%), but urodynamics was infrequently used (3.0%). Of all the overactive bladder medications, anticholinergics were used commonly (17.9% patients), and most patients used anticholinergics alone (without combination therapy). Clean intermittent catheterization (CIC; alone or in combination with medications) was performed in 9.3% of patients, and 3.9% of patients were concomitantly treated with medications. The most common incident complication was lower urinary tract infection (18.1%), which was especially common in patients with open spina bifida (54.1%). Despite guideline recommendations, lower urinary tract dysfunction is not thoroughly evaluated. Adequate understanding of patient status is critical to optimal patient management (behavioral therapy, CIC, and medication) in clinical practice.

Cross-sectional internet survey exploring symptomatic urinary tract infection by type of urinary catheter in persons with spinal cord lesion in Japan.

STUDY DESIGN: Cross-sectional study by members of patient advocacy groups. OBJECTIVES: To evaluate the incidence and frequency of symptomatic urinary tract infection (sUTI) in persons with spinal cord lesion (SCL) using different types of catheters based on an internet survey in Japan. SETTING: An internet survey. METHODS: We conducted an Internet survey of persons with SCL who were considered to be able to perform intermittent self-catheterization (ISC). We evaluated the incidence and frequency of sUTI over the last year in persons performing ISC and those managed by indwelling catheterization (IDC). We also compared the same parameters between persons in the ISC group using reusable silicone catheters and single-use catheters and those with and without a concomitant use of intermittent balloon catheters (i-IDC). RESULTS: Two-hundred and eighty-two persons were analyzed. In the ISC and IDC groups, sUTI occurred in 52.2% and 31.4% of persons (p = 0.021), respectively, in the last year, and the frequencies were 2.8 and 3.5 times a year (p = 0.127), respectively. There were no significant differences in the incidence or frequency of sUTI between persons using reusable catheters and single-use catheters or those with and without the concomitant use of i-IDC. CONCLUSIONS: sUTI occurred in about 1 in 2 persons with SCL performing ISC, which was significantly higher than in the IDC group, and the frequency of sUTI in persons performing ISC was about 3 times a year. The different types of catheters used for ISC were not associated with the incidence or frequency of sUTI. Sponsorship Coloplast Japan Inc.

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

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

[DEVELOPMENT OF JAPANESE TRANSLATION OF THE NEUROGENIC BLADDER SYMPTOM SCORE].

(Objectives) To develop Japanese translations of the standard and short forms of the Neurogenic Bladder Symptom Score (Subjects and methods) The questionnaires were forward translated by a Japanese healthcare professional and non-medical professional and backward translated by two native English-speaking translators. Then, the products were harmonized by the participants involved in the translational processes. Finally, 15 persons with spinal cord lesions were interviewed to improve the provisional Japanese translations based on their suggestions. (Results) Throughout the forward and backward translations and their harmonization, no major translational problems were encountered, other than those attributable to differences in syntax between English and Japanese. The persons could complete the provisional Japanese translations of the standard and short forms in median 7.0 and 3.0 minutes, respectively. Although none of them reported difficulty in answering the questions, 6, 3, and 5 persons pointed out that the tenth question (the seventh question in the short form) and the answers to the nineteenth and twenty-second questions, respectively, were not easy to understand. Taking their suggestions into consideration, we finalized the Japanese translations with the help of a developer of the questionnaire as well as the back-translators. (Conclusions) After a multi-step review process, linguistically valid Japanese translations of the standard and short forms of the Neurogenic Bladder Symptom Score (Neurogenic Bladder Symptom Score Japanese version 1.0) were completed. We hope that these Japanese translations will facilitate future research on patient-reported outcomes in persons with neurogenic lower urinary tract dysfunction.

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

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