Clinical questions in the Japanese Urological Association's 2024 clinical practice guidelines for urethral strictures.

Transurethral procedures such as direct vision internal urethrotomy and urethral dilation have been the traditional treatments for urethral strictures. However, transurethral procedures are associated with high recurrence rates, resulting in many uncured cases and prompting major international urological societies to recommend urethroplasty as the standard treatment owing to its high success rate. In contrast, many Japanese general urologists have little doubts about treating urethral strictures with transurethral treatment. Therefore, urethral stricture treatments in Japan are not in line with those used in other countries. To address this, the Trauma, Emergency Medicine, and Reconstruction Subcommittee of the Japanese Urological Association has developed guidelines to offer standardized treatment protocols for urethral stricture, based on international evidence and tailored to Japan's medical landscape. These guidelines target patients with a clinically suspected urethral stricture and are intended for urologists and general practitioners involved in its diagnosis and treatment. Following the Minds Clinical Practice Guideline Development Manual 2020, the committee identified eight critical clinical issues and formulated eight clinical questions using the "patient, intervention, comparison, and outcome" format. A comprehensive literature search was conducted. For six clinical questions addressed by the existing guidelines or systematic reviews, the level of evidence was determined by qualitative systematic reviews. Quantitative systematic reviews and meta-analyses were performed for the two unique clinical questions. The recommendation grades were determined using the Delphi method and consensus by the committee. These guidelines will be useful to clinicians in daily practice, especially those involved in the care of urethral strictures.

Vibegron shows high efficacy in pediatric patients with refractory daytime urinary incontinence.

PURPOSE: Sparse published reports exist nowadays on vibegron and pediatric overactive bladder, so its usefulness of this agent remains unclear. The purpose of this study was to clarify the effectiveness of vibegron for pediatric cases of daytime urinary incontinence (DUI), including refractory cases. METHODS: Participants comprised 57 patients treated with vibegron for DUI from March 2019 to April 2022. To investigate treatment outcomes and risk factors for pediatric patients with refractory DUI, the following factors were evaluated: age at initiatial administration; frequency of DUI; duration of vibegron treatment; presence of neurodevelopmental disorders (NDDs); presence of constipation; and anticholinergic medications before and after initiation of treatment. RESULTS: Patients included 38 boys and 19 girls with a median age at initial administration of 111 months (range: 64-202 months) and a median administration term of 6 months (range: 1-33 months). With treatment for 6 months, the response rate (complete response + partial response) was 68.3%. A total of 24 cases with NDD showed a 72.0% response rate at 6 months. As for the relationship between anticholinergic agents and vibegron, 15 cases were treated with vibegron as the first choice without anticholinergics (First-choice cases), and 33 cases were treated with vibegron alone after switching from anticholinergics (Switch cases). Vibegron was used in combination with anticholinergic agents in 9 cases (Add-on cases). Response rates at 6 months were 85.0% in First-choice cases, 66.3% in Switch cases, and 40.7% in Add-on cases. Univariate analyses failed to identify any significant risk factors for refractory cases. CONCLUSIONS: Vibegron was effective in pediatric cases of DUI, with efficacy demonstrated within a short time in many cases. Vibegron is expected to play a significant role in the treatment of DUI in pediatric cases.

Girls and renal scarring as risk factors for febrile urinary tract infection after stopping antibiotic prophylaxis in children with vesicoureteral reflux.

PURPOSE: To clarify the incidence of and risk factors for febrile urinary tract infection in children with persistent vesicoureteral reflux (VUR) after the discontinuation of continuous antibiotic prophylaxis (CAP), retrospective chart review was performed. PATIENTS AND METHODS: Among children with primary VUR at 10 years of age or younger at presentation, those who had persistent VUR despite conservative management with CAP and who were subsequently followed after discontinuation of CAP were included. Kaplan-Meier curve and Cox's proportional hazard regression model were used for evaluation of the incidence of and risk factors for febrile urinary tract infection (fUTI) after stopping CAP. RESULTS: Among 144 children (99 boys and 45 girls), fUTI developed in 34. The 5-year fUTI-free rate after discontinuation of CAP was 69.4%. On multivariate analyses, girls (p = 0.008) and abnormalities on nuclear renal scans (p = 0.0019), especially focal defect (p = 0.0471), were significant factors for fUTI. Although the fUTI-free rate was not different between children who had no or 1 risk factor, it was significantly lower in children with 2 risk factors than in those with no or 1 risk factor. CONCLUSIONS: The present study revealed that girls and abnormal renal scan, especially focal defect, are risk factors for fUTI. Active surveillance without CAP for persistent VUR seems to be a safe option for children with no or 1 risk factor. Prophylactic surgery or careful conservative follow-up may be an option for girls with abnormal renal scan results if VUR persists under CAP.

Effect of the occupational environment of parents on cryptorchidism.

BACKGROUND: The early detection and treatment of cryptorchidism are necessary to preserve male fertility. This study aimed to assess the effect of parents' occupational environment on the incidence of cryptorchidism in their sons. METHODS: The study enrolled 51 316 newborn males, whose mothers were recruited in the Japan Environment and Children's Study. We analyzed cryptorchidism incidence in male newborns according to 14 categories of occupation of their parents. We also analyzed the effect of the mother's occupational environment during gestation, including working and night-shift work, on cryptorchidism incidence. Information on occupations was obtained from self-administered questionnaires. Cryptorchidism was identified through a survey at birth or 1 month after birth using medical records. RESULTS: Cryptorchidism was identified in 305 male infants (0.59%) at birth or 1 month after birth. Weight, height, head circumference, and chest circumference at birth were significantly lower in male infants with cryptorchidism than in those without the condition. Gestational age was also shorter in mothers whose infants developed cryptorchidism. Moreover, maternal age at delivery and smoking during gestation also had an effect on cryptorchidism incidence. However, multivariate analysis of the 14 categories of occupation of parents during gestation showed no significant effect on cryptorchidism incidence in their male infants. CONCLUSIONS: This study revealed that the work environment of parents did not significantly affect the incidence of cryptorchidism in their sons. However, this study might have underestimated mild and transient cases of cryptorchidism. Further studies are necessary to investigate the risk factors of cryptorchidism in relation to parents' occupation.

Pediatric congenital hydronephrosis (ureteropelvic junction obstruction): Medical management guide.

The prevalence of asymptomatic hydronephrosis, now detected by ultrasonography, has increased. However, definitive management guidelines for the management of congenital hydronephrosis have not been established. The Japanese Society of Pediatric Urology created a "medical management guide" based on new findings for physicians practicing pediatric urology. We developed a medical management guide focused on congenital hydronephrosis caused by ureteropelvic junction obstruction. This medical management guide consists of the definition, pathophysiology, epidemiology, diagnosis, classification, treatment using a clinical management algorithm of hydronephrosis and the long-term course of the disease. The aim of hydronephrosis management is to determine whether surgery should be carried out to avoid renal dysfunction, as there is a possibility for improvement without intervention. Ultrasonography is essential to make treatment decisions. Management is determined by a comprehensive assessment, including the degree of hydronephrosis, anterior-posterior diameter of the renal pelvis and, if necessary, a nuclear medicine evaluation of the status of urine drainage and renal function.

Risk factors affecting post-pubertal high serum follicle-stimulating hormone in patients with hypospadias.

PURPOSE: The factors affecting spermatogenesis in adulthood in patients with hypospadias (HS) are not clearly understood. In the present study, risk factors affecting post-pubertal high serum follicle-stimulating hormone (FSH) were evaluated in patients with HS. MATERIALS AND METHODS: Among those with a history of HS surgery, patients in whom endocrinological evaluation regarding pituitary-gonadal axis was performed at 15 years of age or older between March 2004 and April 2018 were enrolled in the present study. High serum FSH was defined as greater than 10 mIU/ml. The severity of HS was divided into mild and severe. Factors affecting the post-pubertal high serum FSH were estimated. RESULTS: Seventy-nine patients were included in the present study. The severity of HS was mild in 35 and severe in 44. History of undescended testis (UDT) was confirmed in 12. High serum FSH was detected in nine. On logistic regression model analysis, a history of UDT was the only significant factor for high serum FSH. The incidence of high serum FSH in patients with UDT was significantly higher than that in those without UDT (58.3% vs 7.5%, p < 0.01). When stratified by severity of HS and the presence of UDT, high serum FSH was detected in 70% in patients with severe HS and UDT, whereas less than 10% in other groups. CONCLUSIONS: A history of UDT was a significant factor for post-pubertal high serum FSH in patients with HS. Accordingly, the presence of UDT may be a marker for impaired spermatogenesis in patients with HS, especially in severe cases.

Dopaminergic urethral closure mechanisms in a rat model of Parkinson's disease.

AIMS: Urinary incontinence is prevalent among patients with Parkinson's disease (PD). In the present study, we investigated urethral functions in a rat model of PD induced by 6-hydroxydopamine injection at their substantia nigra pars compacta as well as the roles of selective agonists/antagonist of dopamine D1- and D2-like receptors in active urethral closure mechanisms. METHODS: We measured changes in the urethral pressure amplitude during electrical stimulation, urethral baseline pressure, and leak point pressure after intravenous administration of selective agonists or antagonists of the dopamine D1- and D2-like receptors in a rat model of PD. RESULTS: The mean leak point pressure and the mean active urethral response values were significantly smaller for the untreated PD rat group compared with the control group. In PD model, the active urethral response increased significantly after treatment with the dopamine D1-like receptor agonist, whereas that induced by the dopamine D2-like receptor agonist decreased significantly. The response to the D2-like receptor agonist was suppressed in the PD rat by the dopamine D2-like receptor antagonist. CONCLUSION: Our results suggest that the active urethral closure mechanisms are significantly impaired when dopamine is depleted. In the PD rat, dopamine D1-like receptor activity on the central nervous system appear to partially compensate for urethral functions negatively impacted by the lack of dopamine, whereas dopamine D2-like receptor activity might exacerbate urinary leakage owing to the negative effect of this activated receptor on urethral pressure under increased intra-abdominal pressure.

Effects of prenatal sex hormones on behavioral sexual dimorphism.

BACKGROUND: We investigated the association between the hormone environment during the prenatal period using cord blood, and gender-role play behavior in school-aged children. METHODS: A total of 879 school-aged children (433 boys and 446 girls) in a prospective birth cohort study in Hokkaido were enrolled to analyze the relationship between cord blood level of the sex hormones estradiol (E), testosterone (T), progesterone (P), and dehydroepiandrosterone (DHEA), and the Pre-School Activities Inventory (PSAI) score. The PSAI evaluated sex-typical characteristics, the type of preferred toys and play activities. The PSAI consists of 12 masculine and 12 feminine items, and the composite scores were calculated by subtracting the feminine score from the masculine score. Higher scores indicated male-typical behavior. RESULTS: Composite and masculine PSAI scores were significantly higher in boys. Meanwhile, the feminine score was significantly lower in boys. Although T and P were significantly higher in boys, E/T was significantly higher in girls. In a multivariate regression model, including covariates of social factors, there was no correlation between any of the hormones and PSAI score in boys. In girls, only P and E/T were positively correlated with the feminine score. CONCLUSIONS: Prenatal sex hormone exposure may influence the dimorphic brain development and behavior in school-aged girls. Furthermore, the cord blood hormone levels may not fully reflect the hormone environment during the prenatal period.

Effect of a 5-HT2c receptor agonist on urethral closure mechanisms in female rats.

AIMS: The serotonin (5-HT2c) receptor is known to be involved in the mechanism of urethral closure in a model of stress incontinence. Lorcaserin (Belviq®) has received Food and Drug Administration approval for the treatment of obesity. However, it is unclear whether this selective 5-HT2c receptor agonist enhances urethral closure in stress urinary incontinence (SUI) models. Therefore, we investigated whether lorcaserin could enhance urethral closure in female rats with vaginal distention (VD). METHODS: Normal female rats and rats with stress incontinence induced by VD were tested. We evaluated the effect of a single dose of lorcaserin (0.03, 0.3, or 0.9 mg/kg with cumulative administration) on the urethral pressure amplitude during electrical stimulation (A-URE) and on the urethral baseline pressure (UBP). The manual compression-induced leak point pressure (LPP) was also measured. RESULTS: In VD rats, a single intravenous injection of lorcaserin (0.3 and 0.9 mg/kg) significantly increased both A-URE and LPP compared to saline (P < 0.05). In normal rats, intravenous lorcaserin (0.3 and 0.9 mg/kg) also significantly increased A-URE and LPP compared to saline (P < 0.05). The changes of A-URE and LPP, which are parameters of active urethral closure, were significantly larger in normal rats than in VD rats. CONCLUSIONS: We showed that lorcaserin can activate the external urethral sphincter and pelvic floor muscles, suggesting an influence on active closure mechanisms. 5-HT2c receptors agonists may have dual effects in patients with SUI, not only by reducing obesity but also by enhancing active urethral closure.

Relationship between adrenal steroid hormones in cord blood and birth weight: The Sapporo Cohort, Hokkaido Study on Environment and Children's Health.

OBJECTIVES: We investigated the relationship between steroid hormone levels in cord blood and birth weight. METHODS: Among 514 participants in a prospective birth cohort study in Sapporo, the following hormone levels were measured in 294 stored cord blood samples from 135 males and 159 females: androstenedione, dehydroepiandrosterone (DHEA), cortisol, and cortisone. Birth weight information was obtained from medical records. RESULTS: Androstenedione/DHEA was significantly higher in males than in females, while DHEA was significantly higher in females. Birth weight was significantly higher in males than in females. Regarding cortisone, androstenedione/DHEA, and cortisone/cortisol, a correlation was observed with birth weight in males but not in females. CONCLUSIONS: Prenatal adrenal steroids as well as converting enzymes such as 11ß-hydrosteroid dehydrogenase type 2 and 3ß-hydrosteroid dehydrogenase may have an impact on prenatal physical development.

Prevalence and risk factors of testicular microlithiasis in patients with hypospadias: a retrospective study.

BACKGROUND: It has been described that the incidence of testicular microlithiasis is high in several congenital disorders which may be associated with testicular impairment and infertility. Several reports have shown that a prepubertal or pubertal hormonal abnormality in the pituitary-gonadal axis was identified in some patients with hypospadias that is one of the most common disorders of sex development. However, exact prevalence or risk factors of testicular microlithiasis in patients with hypospadias have not reported so far. In the present study, to clarify the prevalence and risk factors of testicular microlithiasis in patients with hypospadias, a retrospective chart review was performed. METHODS: Children with hypospadias who underwent testicular ultrasonography between January 2010 and April 2016 were enrolled in the present study. Severity of hypospadias was divided into mild and severe. The prevalence and risk factors of testicular microlithiasis or classic testicular microlithiasis were examined. RESULTS: Of 121 children, mild and severe hypospadias were identified in 66 and 55, respectively. Sixteen children had undescended testis. Median age at ultrasonography evaluation was 1.7 years old. Testicular microlithiasis and classic testicular microlithiasis were documented in 17 children (14.0%) and 8 (6.6%), respectively. Logistic regression analysis revealed that presence of undescended testis was only a significant factor for testicular microlithiasis and classic testicular microlithiasis. The prevalence of testicular microlithiasis or classic testicular microlithiasis was significantly higher in children with undescended testis compared to those without undescended testis (testicular microlithiasis; 43.8% versus 9.5% (p = 0.002), classic testicular microlithiasis; 37.5% versus 1.9% (p < 0.001). CONCLUSIONS: The current study demonstrated that the presence of undescended testis was only a significant risk factor for testicular microlithiasis or classic testicular microlithiasis in patients with hypospadias. As co-existing undescended testis has been reported as a risk factor for testicular dysfunction among patients with hypospadias, the current findings suggest that testicular microlithiasis in children with hypospadias may be associated with impaired testicular function. Conversely, patients with isolated HS seem to have lower risks for testicular impairment. Further investigation with longer follow-up will be needed to clarify these findings.

Impact of Preoperative Ultrasonographic Evaluation for Detection of a Viable Testis in Patients With a Unilateral Nonpalpable Testis.

OBJECTIVES: To investigate the impact of preoperative ultrasonography (US) for detecting a viable testis in patients with a unilateral nonpalpable testis. METHODS: Patients with a unilateral nonpalpable testis or unilateral palpable undescended testis who underwent preoperative US were enrolled. Patients were divided into 3 groups as follows: nonpalpable testis/no testis (n = 27), which included patients who had a unilateral nonpalpable testis with no viable testis detected at surgery; nonpalpable testis/viable testis (n = 10), which included patients who had a unilateral nonpalpable testis with a viable testis identified at surgery; and palpable undescended testis (n = 63), which included patients who had a unilateral palpable undescended testis. Preoperative US findings were compared among each group. RESULTS: The testicular volume on the contralateral descended side in the nonpalpable testis/no testis group was significantly greater than that in the nonpalpable testis/viable testis and palpable undescended testis groups. When a testicular volume of 0.54 mL was used as the cutoff value, the sensitivity, specificity, positive predictive value, and negative predictive value for the presence of the affected testis were 75.3%, 100%, 100%, and 60.0%, respectively. The testis on the affected side was detected in none of the nonpalpable testis/no testis group, 7 of the nonpalpable testis/viable testis group, and all of the palpable undescended testis group. When a visible testis on the affected side and a testicular volume of 0.54 mL or less were defined as positive, all patients in the nonpalpable testis/viable testis and palpable undescended testis groups had positive findings versus none in the nonpalpable testis/no testis group. CONCLUSIONS: Preoperative US provides valuable information for predicting the presence of a viable testis in patients with a unilateral nonpalpable testis by estimating both the unaffected testis and the affected side.

Benefits and limitations of animal models in partial bladder outlet obstruction for translational research.

The functions of the lower urinary tract have been investigated for more than a century. Lower urinary tract symptoms, such as incomplete bladder emptying, weak urine stream, daytime urinary frequency, urgency, urge incontinence and nocturia after partial bladder outlet obstruction, is a frequent cause of benign prostatic hyperplasia in aging men. However, the pathophysiological mechanisms have not been fully elucidated. The use of animal models is absolutely imperative for understanding the pathophysiological processes involved in bladder dysfunction. Surgical induction has been used to study lower urinary tract functions of numerous animal species, such as pig, dog, rabbit, guinea pig, rat and mouse, of both sexes. Several morphological and functional modifications under partial bladder outlet obstruction have not only been observed in the bladder, but also in the central nervous system. Understanding the changes of the lower urinary tract functions induced by partial bladder outlet obstruction would also contribute to appropriate drug development for treating these pathophysiological conditions. In the present review, we discuss techniques for creating partial bladder outlet obstruction, the characteristics of several species, as well as issues of each model, and their translational value.

Cord Blood Bisphenol A Levels and Reproductive and Thyroid Hormone Levels of Neonates: The Hokkaido Study on Environment and Children's Health.

BACKGROUND: Bisphenol A (BPA) is widely used and BPA exposure is nearly ubiquitous in developed countries. While animal studies have indicated adverse health effects of prenatal BPA exposure including reproductive dysfunction and thyroid function disruption possibly in a sex-specific manner, findings from epidemiologic studies have not been enough to prove these adverse effects. Given very limited research on human, the aim of this study was to investigate associations between cord blood BPA levels and reproductive and thyroid hormone levels of neonates and whether associations differed by neonate sex. METHODS: The study population included 514 participants of the Hokkaido study recruited from 2002 to 2005 at one hospital in Sapporo, Japan. The BPA level in cord blood was determined by ID-LC/MS/MS, and the limit of quantification was 0.040 ng/ml. We measured nine types of reproductive hormone levels in cord blood, and thyroid hormone levels were obtained from neonate mass screening test data. There were 283 subjects, who had both BPA and hormone levels measurements, included for the final analyses. RESULTS: The geometric mean of cord blood BPA was 0.051 ng/ml. After adjustment, BPA level was negatively associated with prolactin (PRL) (ß = -0.38). There was an interaction between infant sex and BPA levels on PRL; a weak negative association was found in boys (ß = -0.12), whereas a weak positive association was found in girls (ß = 0.14). BPA level showed weak positive association with testosterone, estradiol, and progesterone levels in boys. No association was found between BPA and thyroid hormone levels. CONCLUSIONS: Our findings suggested that fetal BPA levels might be associated with changes in certain reproductive hormone levels of neonates in a sex-specific manner, though further investigations are necessary.

Prevalence of and risk factors for symptomatic urinary tract infection after endoscopic incision for the treatment of ureterocele in children.

OBJECTIVE: To clarify the impact of endoscopic incision (EI) for ureterocele as an initial procedure, by performing a retrospective chart review, focusing on the prevalence of and risk factors for symptomatic urinary tract infection (UTI) after EI. MATERIALS AND METHODS: In the present study we included children with ureterocele, managed between September 1994 and April 2016, who were observed conservatively without additional surgical management after EI. Ureterocele was categorized as intravesical or ectopic. Symptomatic UTI was defined as either recurrent non-febrile or febrile UTI. The prevalence of and risk factors for symptomatic UTI were analysed using Cox proportional hazard models or Kaplan-Meier curves, and the log-rank test. RESULTS: A total of 36 children met the inclusion criteria. The median age of the participants at EI was 8.9 months. Eleven children had symptomatic UTIs (febrile, n = 9; recurrent non-febrile, n = 2) during the median follow-up of 75.5 months. Initial symptomatic UTI in each child occurred <25 months after EI. The symptomatic UTI-free rate after EI was 65.6%. The risk factors for symptomatic UTI were female gender, duplex system, ectopic ureterocele, and unchanged hydronephrosis after EI. CONCLUSIONS: The present study determined the critical period and risk factors for symptomatic UTI after EI for the treatment of ureterocele. The results suggest that when conservative management is indicated after EI, patients, especially those with risk factors, should be followed carefully at least for 25 months after EI for symptomatic UTI.

Radical prostatectomy restores detrusor contraction pattern according to pressure flow parameters.

OBJECTIVES: Pressure flow studies are regarded as the gold standard for evaluating both bladder outlet obstruction and detrusor contractility, but none of the current methods for evaluating bladder contraction patterns are well validated. Impaired bladder contraction results in a lower peak Watts factor and poorly sustained detrusor contractions. From this viewpoint, the maximum Watts factor and its pattern should be considered separately. To examine detrusor contraction pattern in patients after radical prostatectomy by using multiple parameters. METHODS: A total of 37 patients with clinically localized prostate cancer underwent both pre- and post-radical prostatectomy urodynamic evaluations. The examined urodynamic parameters included the maximum flow rate, post-void residual volume, detrusor pressure at maximum flow, maximum Watts factor and relative volume (maximum Watts factor). Some parameters were defined from the Watts factor curve throughout micturition. Relative volume (maximum Watts factor) was the relative bladder volume at the maximum Watts factor. A normal detrusor contractility pattern involves an increase in Watts factor at the initiation followed by further gradual increases until the end of micturition. RESULTS: Maximum flow rate increased significantly after radical prostatectomy (pre: 13.0 ± 6.5, post: 17.3 ± 7.7 mL/min; P < 0.01), whereas detrusor pressure at maximum flow and post-void residual volume decreased significantly (pre: 49.6 ± 21.6 and 31.4 ± 18.2 cmH2 O; post: 48.6 ± 66.1 and 10.1 ± 28.5 mL; P < 0.05). Maximum Watts factor did not change significantly after radical prostatectomy (pre: 10.5 ± 3.1 W/m2 , post: 11.0 ± 3.2 W/m2 ), but relative volume (maximum Watts factor) decreased significantly (pre: 0.48 ± 0.3, post: 0.20 ± 0.20; P < 0.001). Maximum Watts factor represents the maximum power of bladder contraction at a particular point in time, whereas relative volume (maximum Watts factor) can be used to detect changes in detrusor contraction pattern. CONCLUSIONS: Evaluation of relative volume (maximum Watts factor) confirms that radical prostatectomy restores the normal detrusor contractility pattern in prostate cancer patients.

Factors affecting post-pubertal penile size in patients with hypospadias.

OBJECTIVES: To evaluate actual post-pubertal penile size and factors affecting it in hypospadias patients, we retrospectively reviewed medical charts. PATIENTS AND METHODS: Hypospadias patients whose external genitalia were categorized into Tanner stage 5, and whose stretched penile length was evaluated at 15 years old or older from April 2008 to April 2015, were enrolled in the present study. Stretched penile length was measured by a single examiner. Actual post-pubertal stretched penile length and factors affecting the post-pubertal stretched penile length were estimated. Statistical analysis was performed using Mann-Whitney U test and univariate and multivariate linear regression models for the determination of independent factors. RESULTS: Thirty patients met the inclusion criteria. Median age at evaluation was 17.2 years. Thirteen and 17 had mild and severe hypospadias, respectively. Endocrinological abnormality was identified in 5. Multivariate analysis showed that the severity of hypospadias and endocrinological abnormality were significant factors affecting stretched penile length. Stretched penile length in 25 patients without endocrinological abnormality was significantly longer than that in those with endocrinological abnormality (p = 0.036). Among patients without endocrinological abnormality, stretched penile length in 13 with severe hypospadias was significantly shorter than that in 12 with mild hypospadias (p = 0.004). CONCLUSIONS: While the severity of hypospadias and endocrinological abnormality at post-pubertal evaluation were factors affecting post-pubertal penile size, stretched penile length in patients with severe hypospadias was shorter even in cases without endocrinological abnormality. These results suggest that severe hypospadias is not only a disorder of urethral development, but also a disorder of penile development.

The inflammatory cytokine IL-1ß is involved in bladder remodeling after bladder outlet obstruction in mice.

AIMS: We investigated the relationship between IL-1ß and morphological and functional changes following partial bladder outlet obstruction (pBOO). METHODS: Female wild-type C57/BL6 mice (WT) and IL-1ß-/- mice (KO) were used. Animals were sacrificed either 1 or 3 weeks after pBOO or sham surgery, and their bladders were harvested to determine bladder weight, for RT-PCR to measure interleukin-1ß (IL-1ß), insulin growth factor-1 (IGF-1), and transforming growth factor-ß (TGF-ß) levels, and for histological analysis with Hematoxylin-Eosin (HE) staining. Cystometry was performed on conscious animals 3 weeks after surgery to evaluate urodynamic parameters. IGF-1 was also administered intraperitoneally to KO with pBOO, and bladder weight was then investigated. RESULTS: IL-1ß-mRNA levels were significantly higher in WT-pBOO than in WT-sham. IGF-1-mRNA and TGF-ß-mRNA levels were also significantly higher in WT-pBOO than in WT-sham; however, these increases were smaller in KO-pBOO than in WT-pBOO. Bladder weight was significantly higher in WT-pBOO than in WT-sham, while increases in bladder weight were significantly suppressed in KO-pBOO. HE staining revealed the thickened bladder wall in WT-pBOO, and this phenomenon was less in KO-pBOO than in WT-pBOO. Regarding the urodynamic parameters examined, micturition pressure and bladder capacity were significantly higher in WT-pBOO than in WT-sham, but remained unchanged in KO-pBOO. The administration of IGF-1 to KO-pBOO led to similar increases in bladder weight and the thickened bladder wall as those observed in WT-pBOO. CONCLUSION: IL-1ß has the potential to induce bladder remodeling and deteriorate urodynamic parameters in pBOO.

The role of serotonergic mechanism in the rat prefrontal cortex for controlling the micturition reflex: An in vivo microdialysis study.

AIMS: To investigate the role of the PFC in the micturition reflex using an in vivo microdialysis study in rats. METHODS: Adult female Sprague-Dawley rats were used and microdyalysis in the PFC and cystometrography (CMG) were performed under consciousness and free movement in the present study. Experiment 1: Samples including extracellular neurotransmitters were collected by microdyalysis and analyzed by high performance liquid chromatography. At the same time, CMG were performed to measure intercontraction interval (ICI) and maximum voiding pressure (MVP). Experiment 2: SSRI (citalopram, 1 µM) was administered into the PFC, and microdyalysis and cystometrography (CMG) were performed simultaneously. Experiment 3: Following SSRI administration, 5-HT1A agonist (8-OH-DPAT, 300 µM), which has the effect of decreasing the level of serotonin (5-HT) in the PFC, was administered into the PFC, and microdyalysis and CMG were performed simultaneously. RESULTS: Experiment 1: Extracellular level of 5-HT in the PFC significantly increased during micturition reflex (P < 0.05), whereas levels of glutamate or dopamine were not significantly changed. Experiment 2: Local administration of SSRI in the PFC increased the 5-HT level up to approximate 600% of the basal level. It also significantly increased ICI (P < 0.05), whereas no significant change was found in MVP. Experiment 3: The extracellular level of 5-HT gradually decreased after local administration of 5-HT1A agonist, thereby ICI significantly decreased (P < 0.05). CONCLUSIONS: The results of the present study suggest that the PFC has a suppressive effect on neural control of the micturition reflex via serotonin. Neurourol. Urodynam. 35:902-907, 2016. © 2015 Wiley Periodicals, Inc.

Differences in neurotransmitter systems of ventrolateral periaqueductal gray between the micturition reflex and nociceptive regulation: An in vivo microdialysis study.

OBJECTIVES: To elucidate the possible involvement of glutamate and serotonin (5-hydroxytryptamine) neurons in the ventrolateral midbrain periaqueductal gray during noxious stimulation. METHODS: The study was carried out by evoking a noxious stimulation by acetic acid in an animal model of cystitis. Changes in glutamate and 5-hydroxytryptamine in the periaqueductal gray during the micturition reflex and acetic acid-induced cystitis were determined using in vivo microdialysis combined with cystometry in rats. RESULTS: Extracellular glutamate levels slightly, but significantly, increased during the micturition reflex induced by saline infusion into the bladder. Intravesical infusion of acetic acid facilitated the micturition reflex characterized by increases in voiding pressure and decreases in the intercontraction interval. Glutamate levels were markedly increased by acetic acid, and this enhancement was sustained for at least 3 h. 5-Hydroxytryptamine levels, which were not altered during the micturition reflex, were increased after intravesical infusion of acetic acid. CONCLUSION: The results suggest that periaqueductal gray glutamate and 5-hydroxytryptamine neurons differentially participate in the modulation of both nociception and the micturition reflex. Furthermore, periaqueductal gray 5-hydroxytryptamine levels appear to reflect the nociceptive stimuli.