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Introduction Hemiscrotal agenesis is a rare scrotal developmental disorder. Orchiopexy on the opposite side of the scrotum with rugae or scrotoplasty combined with orchiopexy is usually performed as a surgical treatment for hemiscrotal agenesis with cryptorchidism. Till date, there are only eight published case studies of hemiscrotal agenesis. Case presentation A 6‐year‐old boy, who had been previously treated for infantile hemangiomas, was referred by a pediatrician to our hospital for the follow‐up of hemiscrotal agenesis without cryptorchidism. Thermography demonstrated that the temperature of the right scrotal skin with no rugae was higher than that of the left scrotal skin with rugae. The patient's parent declined scrotoplasty because the hemiscrotal agenesis was to be followed up without scrotoplasty and scrotal ultrasonography revealed no abnormal findings in both testes. Conclusion High‐temperature environment may not impair the testicular growth in prepubertal hemiscrotal agenesis without cryptorchidism.

Reports of hydronephrosis-induced hypertension in pediatric patients are rare. A 7-year-old girl with hypertension was referred to our hospital with left hydronephrosis caused by ureteropelvic junction obstruction of the lower moiety in a partial duplex system. Because the lower moiety was almost nonfunctional, a laparoscopic heminephrectomy was performed. Antihypertensive drugs were unnecessary on the day after surgery. This is the first report of a Page kidney in a patient with ureteropelvic junction obstruction of the lower moiety. The cause of hypertension was evaluated based on the plasma renin activity and pathological findings of the lower moiety.

Introduction Ureteropelvic junction obstruction is often associated with renal calculus formation. However, there is no report of using robot‐assisted laparoscopic pyeloplasty combined with percutaneous endoscopic surgery for ureteropelvic junction obstruction and renal calculi in a partial duplex system. Case presentation A 19‐year‐old female patient with lower moiety ureteropelvic junction obstruction and renal calculi in a partial duplex system was referred to our hospital because of left lumbar pain, left acute pyelonephritis, and an increase in left renal calculi during follow‐up at the referral hospital. To prevent the complication of percutaneous nephrolithotripsy following pyeloplasty, robot‐assisted laparoscopic pyeloplasty combined with percutaneous endoscopic surgery was performed. Two years after surgery, the patient reported no left lumbar pain. Conclusion The combination of robot‐assisted laparoscopic pyeloplasty and percutaneous endoscopic surgery can be proposed as a safe and less‐invasive treatment option for ureteropelvic junction obstruction and renal calculi in a partial duplex system.

Introduction Crossed fused renal ectopia is rare and usually asymptomatic. However, it is associated with urological anomalies. Case presentation A 15‐year‐old Japanese boy was transported to our hospital with right abdominal pain and hematuria after a soccer ball hit his right abdomen. Computed tomography revealed right hydronephrosis beyond the center of the body and no left kidney. Percutaneous nephrostomy was performed immediately, and a pyeloplasty was scheduled for 5 months later. Right hydronephrosis was noted to have been caused by left pelvic expansion due to a crossed fused ectopic kidney (secondary to a left pelviureteric junction obstruction). Subsequently, a left dismembered pyeloplasty was performed. Twenty‐four months later, pain and hematuria were absent, and the creatinine level was 1.1 mg/dL. Ultrasonography revealed a shrunken right kidney. Conclusion We encountered a unique urological anomaly with crossed fused renal ectopia. Comprehensive anatomical evaluation before surgery is important for maintaining long‐term renal function.

Background: Urethral prolapse is defined as the eversion of the urethral mucosa at the level of the urethral meatus. It commonly presents as a vulvar mass, followed by bleeding and dysuria. However, no studies have reported on perioperative uroflowmetry results for pediatric urethral prolapse patients with dysuria. Herein, we report a urethral prolapse pediatric patient with dysuria who was successfully treated through surgery. Case presentation: A 5-year-old Asian girl complained of difficulty voiding for 6 months. Her mother discovered a bulging mass over her urethra. Uroflowmetry revealed a plateau-shaped curve. Conservative treatments were not effective, and abnormal UFM and dysuria continued. After surgery using the modified Kelly-Burnum method, symptoms resolved, and uroflowmetry parameters normalized. Conclusions: This is the first comparison of the pre- and post-operative uroflowmetry results of a pediatric patient with urethral prolapse. Uroflowmetry is a non-invasive tool useful for managing urethral prolapse in pediatric patients with dysuria.

Abstract Aim Supporting patients upon discharge following prolonged hospitalization in private psychiatric hospitals in Japan have long been an issue. This study evaluated the efficacy of clozapine in treating long‐stay patients with treatment‐resistant schizophrenia to reduce the frequency and duration of readmissions postdischarge. Methods We retrospectively examined the length and frequency of hospitalizations of long‐stay and non‐long‐stay patients with schizophrenia who were introduced to clozapine at our hospital. Results Comparing participants’ medical records 2 years before and after the introduction of clozapine, we identified a significant decrease in both length and frequency of hospitalizations in all patients who were introduced to clozapine. In long‐stay patients, the length and frequency of hospitalization were significantly reduced. However, compared to non‐long‐stay patients, the period from introduction of clozapine to discharge was longer and the dose of clozapine was higher. Thus, it is necessary to take time to evaluate the therapeutic effects for long‐stay patients. Conclusion The results showed that clozapine is helpful for patients with treatment‐resistant schizophrenia, who are considered difficult to treat and discharge in Japan.

Introduction The reimplantation of an ectopic ureter is still performed as an open surgery, although laparoscopic or robot‐assisted laparoscopic surgery has gained popularity as a minimally invasive treatment for pediatric urological disorders. Case presentation A 15‐day‐old Japanese boy was referred to our hospital with right hydronephrosis. A detailed examination revealed complete ureteral duplication on the right side and a dilated ectopic upper pole ureter, opening into the prostatic urethra. Since the patient had recurrent febrile urinary tract infections, we performed plication and ureteral reimplantation of the dilated ectopic ureter using a transvesicoscopic surgical method at the age of 2 years and 5 months. Conclusion We safely performed transvesicoscopic ureteral reimplantation for an ectopic upper pole ureter with a mate ureter in a duplex kidney, following the detection of an ectopic ureter within the bladder, due to the prior understanding of the wrapping of both ureters in a common sheath.

Urgent scrotal exploration is performed for segmental testicular infarction (STI) because malignant testicular tumors cannot be ruled out even when STI is suspected on color Doppler ultrasound (US). This report describes the case of a 14-year-old boy who was successfully diagnosed with STI associated with epididymitis using color Doppler US to avoid radical orchiectomy. To our knowledge, this is the first report of STI being diagnosed during puberty and managed using color Doppler US and contrast-enhanced magnetic resonance imaging-guided conservative treatment.

Ureterocele prolapse, an unusual but distinctive finding, may cause voiding difficulty. A 6-year-old male patient was referred to our hospital after his mother discovered that he tapped his lower abdomen when his urinary stream was interrupted during voiding. Voiding cystourethrography indicated a ureterocele prolapse causing the intermittency of voiding; therefore, transvesicoscopic ureteral reimplantation with ureterocelectomy was performed and the voiding consequently improved. However, this condition would not have been diagnosed had the unusual voiding behavior gone unnoticed. Therefore, diagnosing congenital bladder obstructions could be challenging if a patient adapts to a voiding difficulty.

Introduction Primary obstructed non‐refluxing megaureter, a type of congenitally dilated ureter, often resolves spontaneously. Surgery may be indicated in symptomatic cases; however, there are no reports of transvesicoscopic ureteral implantation and ureteroscopy for ureteral stones. Therefore, we describe the treatment of primary obstructed non‐refluxing megaureter and ureteral calculi using this technique. Case presentation A 6‐year‐old Japanese girl was referred for abdominal pain and gross hematuria due to right megaureter with multiple stones in the renal lower‐pole calyces and ureter. She was diagnosed with primary obstructed non‐refluxing megaureter and ureterovesical junction obstruction. The stones were removed using mini‐percutaneous nephrolithotomy and transvesicoureteroscopic surgery, respectively. A narrow segment of the right ureter was cut, and transvesicoscopic ureteral plication and reimplantation were performed. The procedures were successful without postoperative complications. Conclusion Transvesicoscopic ureteral reimplantation with ureteroscopy may be a safe, effective and minimally invasive surgical option for ureterovesical junction obstruction with ureteral stones.

Abstract Background To investigate the efficacy and safety of endoscopic injection therapy for vesicoureteral reflux in post-pubertal patients with dilated ureteral orifice via modified hydrodistension implantation techniques. Methods We retrospectively reviewed medical records including operational procedure and clinical course of all consecutive patients over 12 years old with a history of injection therapy. Endoscopic injection of dextranomer/hyaluronic acid copolymer was performed under hydrodistension implantation technique with some modifications in order to inject through dilated ureteral orifice align with the intramural ureter. Technical selections were done according to hydrodistension grade of the ureteral orifice. Voiding cystourethrography was evaluated at 3 months postoperatively. Hydronephrosis was evaluated using ultrasonography preoperatively until 6 months postoperatively. Results From 2016 to 2019, 12 patients (all female, 16 ureteral units; median age 32 [range 15–61] years) underwent endoscopic injection therapy at one of our institutions. We have identified grade II vesicoureteral reflux in 5 ureters, grade III in 8, and grade IV in 3 ureters. Grade 3 ureteral-orifice dilation were presented in 12 ureters (75%), grade 2 in 3 and grade 1 in 1 ureter in the present cases. Postoperatively, vesicoureteral reflux was diminished to grade 0 in 12 ureteral units (75%), decreased to grade I in 3 (9%), and remained grade III in 1 (6%). Three patients reported dull flank pain for several days postoperatively and there was 1 case of acute pyelonephritis. Temporary hydronephrosis was confirmed in 3 ureteral units (19%) at 1 month postoperatively. Median follow-up duration was 23 (range 13–63) months long. Although, 3 patients were experienced f-UTI 1–2 times, repeated VCUG showed no VUR recurrence. Conclusions According to hydrodistension grade of the ureteral orifice, endoscopic injection therapy via modified hydrodistension implantation technique is an effective and safe treatment for vesicoureteral reflux in post-pubertal female patients with dilated ureteral orifice. While ureteral deformities or a history of anti-reflux surgery may increase the risks, these can be managed with appropriate methods that ensure sufficient mound appearance and height.

Abstract Background Myelomeningocele, which causes a neurogenic bladder, is usually treated with anticholinergics in children with neurogenic detrusor overactivity (NDO); however, anticholinergics cause side effects such as dry mouth, constipation, attention deficit, and inadequate reduction in detrusor leak point pressure. Vibegron, a novel selective beta-3 adrenoreceptor agonist, is a well-established alternative to anticholinergics in adults with an overactive bladder. It remains unknown whether this agent can be used for pediatric patients. We report the case of a girl with anticholinergic-resistant NDO due to tethered cord syndrome after myelomeningocele repair, who was treated with vibegron. Case presentation A 4-year-old Filipino girl had increased frequency of daytime urinary incontinence and foul-smelling urine since the age of 3. Clinical examination revealed constipation, and urinalysis revealed bacteriuria. Voiding cystourethrography revealed an enlarged and trabeculated bladder without vesicoureteral reflux. On the urodynamic study (UDS), she was found to have detrusor overactivity (DO) and low bladder compliance. She could not void and was diagnosed with overflow incontinence. Clean intermittent catheterization (CIC) and orally administered propiverine (0.8 mg/kg/day) were initiated, and urinary incontinence was resolved. She underwent a UDS annually; the UDS at 6 years of age still revealed DO and low bladder compliance in spite of receiving propiverine. The treatment was switched from propiverine to vibegron (1.4 mg/kg/day). On the UDS after a 5-week treatment schedule of vibegron, the DO disappeared and the bladder compliance improved. CIC and orally administered vibegron have been continued for 7 months so far, and she has had no urinary tract infection with no drug-related adverse events. Conclusions Vibegron was effective and well tolerated in the treatment of a pediatric patient with NDO. Vibegron improved the urodynamic parameters for anticholinergic-resistant neurogenic bladder. This agent can be a beneficial and preferable alternative therapeutic agent to anticholinergics in patients with anticholinergic-resistant NDO.

Abstract Background Transverse testicular ectopia (TTE) is a rare anomaly in which both testes descend through a single inguinal canal into the same hemiscrotum. Although almost 20–50% of patients with TTE exhibit persistent Müllerian duct syndrome (PMDS) and many genetic analyses have been performed, no reports have described the genes contributing to TTE without PMDS. Here, we report two cases of TTE without PMDS using immunohistochemical staining and genetic analysis. Case presentation Two Asian patients with TTE without PMDS were subjected to orchiopexy. We performed testicular biopsies during operation and obtained blood samples before the operation. Testicular tissues were stained for c-kit, placental alkaline phosphatase (PLAP), and undifferentiated embryonic cell transcription factor 1 (UTF1) to evaluate the presence of intratubular malignant germ cells. Additionally, we performed polymerase chain reaction-based direct sequencing to identify single nucleotide polymorphisms in genes associated with regression of the Müllerian duct and testicular descent (that is, anti-Müllerian hormone [AMH], AMH receptor 2 [AMHR2], insulin-like 3 [INSL3], and relaxin family peptide receptor 2 [RXFP2]). The three-dimensional structures of proteins were predicted using SWISS-MODEL. In immunohistochemical analysis, c-kit and UTF1 were positive, whereas PLAP was negative in three testicular tissue samples from the two patients. These features were also detected on the unaffected side. In variant analysis, common missense variants in the AMH gene (g.365G>T; c.165G>T; p.Ser49Ile [rs10407022]) were observed. All variants in INSL3 and RXFP2 genes were intronic or silent. Conclusions Because UTF1, a specific marker of spermatogonial stem cell activity, was expressed in both the affected and unaffected sides in the testicular tissues of two patients, the risk of malignancy may be high in these patients. Although the etiology of TTE without PMDS remains unclear, our variant analysis results were consistent with previous reports, and variants in the AMH gene (rs10407022) may contribute to the specific phenotype of TTE without PMDS.

Abstract Background Most cases of antenatal the Society of Fetal Urology (SFU) grade 1or 2 hydronephrosis (HN) improve or resolve spontaneously with conservative treatment. However, there is no consensus on the duration of follow-up for cases of grade 1or 2 HN. The aim of this study was to determine the need for continuous follow-up period and new management of children with antenatal grade 1or 2 HN. Methods Subjects underwent ultrasonographic assessment for HN according to the SFU classification. We retrospectively evaluated 112 patients with postnatal grade 1 HN and 69 with grade 2 HN using abdominal ultrasonography between January 2010 and December 2017. We examined the change in HN grade on repeat ultrasonography. Kaplan–Meier method was used to show the effect of HN grade on the rate of HN changes. Results The mean follow-up duration was 44.9 ± 36.4 months (range 12–274). Initial SFU grade 1 HN disappeared in 47.0% of cases at 12 months, 66.4% at 24 months and 73.2% at 48 months. Initial SFU grade 2 HN showed improvement in grade in 74.7% of cases at 12 months, 88.3% at 24 months and 89.5% at 48 months. However, 14.6% of SFU grade 1 and 2.8% of SFU grade 2 cases increased in grade and of the 17 cases, 16 cases worsened within the first 6 months. No cases with increased grade required pyeloplasty. Initial disappearance and later reappearance of HN occurred in 40.5% of SFU grade 1 and 2 cases. The mean duration of later reappearance of HN was 39.1 ± 36.2 months (range 12–137). No cases showed reappearance of HN after more than 1 year. Conclusions Ultrasonography within the first 6 months was necessary for management of children with antenatal grade 1or 2 HN, because some patients showed worsening. After that, it is considered safe to spread the follow-up interval for stable cases. Most cases of grade 1or 2 HN resolved spontaneously, however a few cases reappeared within 1 year. Therefore, ultrasonography after 1 year was necessary in children with HN that spontaneously disappeared. The appropriate time to end the follow-up was considered to have been after 1 year or more has passed since the disappearance was confirmed.

Posterior urethral valves (PUVs) are the most common cause of congenital urethral obstruction. However, the diagnosis of a PUV is sometimes difficult. A 13-year-old Japanese boy and his mother visited our hospital, and his mother complained that he frequently strained to void although he had no complaint. Uroflowmetry revealed a plateau-shaped curve and a voiding cystourethrography (VCUG) revealed a PUV. Thus, we performed a transurethral incision of the PUV, and his voiding status improved. Because some patients with mild PUV may not notice their dysuria, we believe that VCUG should be performed without hesitation when a urethral lesion is suspected.

Background: We previously discovered that renal macrophages (Mφs) phagocytose renal calcium oxalate monohydrate (COM) crystals. This study investigated the processing of engulfed crystals using in vitro models. Methods: J774.1 mouse Mφs were exposed to COM crystals and observed for 24 h using polarized light microscopy with/without cytochalasin B (CB), an inhibitor of phagocytosis, to confirm active crystal phagocytosis. LysoTracker and immunohistochemical staining using transmission electron microscopy for lysosomal-associated membrane protein 1 were used to confirm engulfed COM crystal uptake into lysosomes. Diachronic tracking of specific Mφs was performed to capture the entire course of engulfed COM crystal processing using polarized light microscopy. Follow-up studies of fluorescent COM (f-COM) crystals using imaging cytometry were performed in the presence and absence of nigericin to dissipate the pH gradient in acidic organelles. Results: Phagocytosis rates increased with COM density and were significantly lower in cells treated with CB (p < 0.01). We observed that engulfed crystals colocalized within lysosomes of the Mφs; moreover, diachronic observation indicated that the engulfed COM crystals were subdivided during Mφ division and eliminated by the 7th day of culture. Additionally, imaging cytometry showed that the fluorescence level of f-COM crystals in the nigericin (–) group after 48 h was significantly lower than that in the nigericin (+) group. Conclusions: This study confirmed active phagocytosis and lysosomal processing of engulfed COM crystals by Mφs. This discovery is expected to contribute to the development of future drugs that enhance the COM crystal phagocytic ability of Mφs.

Abstract Background We investigated the impact of postoperative membranous urethral length and other anatomic characteristics of the pelvic floor shape as measured by magnetic resonance imaging on the improvement in continence following robotic-assisted radical prostatectomy. Methods We retrospectively reviewed data from 73 patients who underwent postoperative prostate magnetic resonance imaging following robotic-assisted radical prostatectomy between 2013 and 2018. Patient demographics; pre-, peri-, and post-operative parameters; and pelvic anatomic features on magnetic resonance imaging were reviewed. Patients who used no urinary incontinence pads or pads for protection were considered to have achieved complete continence. Results Urinary continence was restored in 27.4, 53.4, 68.5, and 84.9% of patients at 1, 3, 6, and 12 months after robotic-assisted radical prostatectomy, respectively. When patients were divided into early and late continence groups based on urinary continence at 3 months after robotic-assisted radical prostatectomy, no significantly different clinical characteristics or surgical outcomes were found. However, the mean membranous urethral length (18.5 mm for the early continence group vs. 16.9 mm for the late continence group), levator muscle width (7.1 vs. 6.5 mm, respectively), and bladder neck width on the trigone side (7.2 mm vs. 5.4 mm, respectively) were significantly different between groups (all p

The incidence of male reproductive system disorders, especially hypospadias, has been increasing in developed countries since the latter half of the 20th century. Endocrine-disrupting chemicals from the environment are considered to be involved in hypospadias onset through epigenetic alterations. This pilot study aimed to explore disease-specific methylated CpGs in human patient samples using the methylated-site display-amplified fragment length polymorphism (MSD-AFLP) technique developed by our research group [1]. We compared clinical samples from hypospadias and phimosis patients. Foreskin and blood samples were collected from one- to two-year-old patients with hypospadias (N = 3) and phimosis (N = 3) during surgical treatment. MSD-AFLP analysis showed significantly decreased CpG-methylation levels of genes such as MYH11 and increased CpG-methylation levels of genes such as PLA2G15 in hypospadias patients. Hierarchical clustering analysis showed that genes with significantly altered CpG levels were more markedly altered in DNA from blood than from foreskin. Because of the small number of samples, further investigation is necessary to elucidate the association between variations in CpG levels in foreskin and blood DNA and male genital abnormalities. However, our MSD-AFLP method appears to be a useful tool for exploring disease-specific methylated-CpGs in human epidemiological studies.

Abstract Background We investigated the renoprotective ability of healthy people against kidney stone formation. To clarify intratubular crystal kinetics and processing in human kidneys, we performed a quantitative and morphological observation of nephrectomized renal parenchyma tissues. Methods Clinical data and pathological samples from 60 patients who underwent radical nephrectomy for renal cancer were collected from June 2004 to June 2010. The patients were retrospectively classified as stone formers (SFs; n = 30, kidney stones detected by preoperative computed tomography) and non-stone formers (NSFs; n = 30, no kidney stone history). The morphology of parenchymal intratubular crystals and kidney stone-related gene and protein expression levels were examined in noncancerous renal sections from both groups. Results SFs had a higher smoking rate (P = 0.0097); lower red blood cell, hemoglobin, and hematocrit values; and higher urinary red blood cell, white blood cell, and bacterial counts than NSFs. Scanning electron microscopy revealed calcium-containing crystal deposits and crystal attachment to the renal tubular lumen in both groups. Both groups demonstrated crystal transmigration from the tubular lumen to the interstitium. The crystal diffusion analysis indicated a significantly higher crystal existing ratio in the medulla and papilla of SFs and a significantly higher number of papillary crystal deposits in SFs than NSFs. The expression analysis indicated relatively high osteopontin and CD68, low superoxide dismutase, and significantly lower Tamm–Horsfall protein expression levels in SFs. Multivariate logistic regression analysis involving the above factors found the presence of renal papillary crystals as a significant independent factor related to SFs (odds ratio 5.55, 95% confidence interval 1.08–37.18, P = 0.0395). Conclusions Regardless of stone formation, intratubular crystals in the renal parenchyma seem to transmigrate to the interstitium. SFs may have reduced ability to eliminate renal parenchymal crystals, particularly those in the papilla region, than NSFs with associated gene expression profiles.

Abstract Background Pheochromocytomas are rare neuroendocrine tumors, with a malignancy frequency of approximately 10%. The treatment of malignant pheochromocytoma is palliative, and the traditional management strategy has limited efficacy. Furthermore, no clear criteria exist for the treatment of metastatic pheochromocytoma, especially for unresectable lesions. We report a case of complete remission of metastatic pheochromocytoma in 123I-metaiodobenzylguanidine (MIBG) scintigraphy after a single session of 131I-MIBG therapy. Case presentation A 61-year-old woman had a right adrenal grand tumor and lymph node metastasis on the hilum of the right kidney, both of which incorporated MIBG. After surgery, immunostaining of a tumor specimen showed expression of the tumor makers chromogranin and synaptophysin. One year postoperatively, abdominal computed tomography revealed a local recurrence and retroperitoneal lymph node swelling. The local recurrence was positive for MIBG uptake, whereas the swollen retroperitoneal lymph nodes were negative. She underwent surgery again, but the local recurrence was unresectable because of rigid adhesion to the surrounding tissue. Immunostaining of an intraoperatively extracted swollen retroperitoneal lymph node showed expression of tumor markers. The patient then underwent a single session of 131I-MIBG therapy (7.4 GBq, 200 mCi), after which the residual lesions no longer incorporated MIBG, and a complete response in 123I- metaiodobenzylguanidine (MIBG) scintigraphy was achieved. The 131I-MIBG treatment was repeated 6 months later. None of the lesions were positive for MIBG uptake. Conclusions 131I-MIBG therapy efficaciously treats unresectable lesions that are positive for MIBG uptake.

Abstract Background Congenital anomalies of the kidney and urinary tract (CAKUT), such as renal dysplasia, hydronephrosis, or vesicoureteral reflux, are the most common causes of end-stage renal disease. However, the genetic etiology of CAKUT remains unclear. In this study, we performed whole exome sequencing (WES) to elucidate the genetic etiology of symptomatic CAKUT and CAKUT accompanied by cryptorchidism. Methods Three patients with unilateral renal dysplasia accompanied by ipsilateral cryptorchidism were included in this analysis. Genomic DNA was extracted from peripheral blood, and WES was performed. Disease-specific single nucleotide polymorphisms (SNPs) were determined by comparison with the human genome reference sequence (hg19). Additionally, we searched for SNPs that were common to all three patients, with a particular focus on the coding regions of the target genes. Results In total, 8710 SNPs were detected. Of the genes harboring these SNPs, 32 associated with renal or testicular development were selected for further analyses. Of these, eight genes (i.e., SMAD4, ITGA8, GRIP1, FREM1, FREM2, TNXB, BMP8B, and SALL1) carried a single amino acid substitution that was common to all three patients. In particular, SNPs in SMAD4 (His290Pro and His291Pro) have not been reported previously in patients with symptomatic CAKUT. Of the candidate genes, four genes (i.e., ITGA8, GRIP1, FREM1, and FREM2) were Fraser syndrome-related genes, encoding proteins that functionally converged on the glial cell-derived neurotrophic factor/RET/bone morphogenic protein (BMP) signaling pathways. As another candidate gene, the protein encoded by BMP8B activates the nuclear translocation of SMAD4, which regulates the expression of genes associated with the differentiation of primordial germ cells or testicular development. Additionally, BMP4, a member of the BMP family, regulates the interaction between metanephric mesenchyme and ureteric buds by suppressing GDNF. Conclusions Taken together, our findings suggested that the development of the kidney and urinary tract is intimately linked with that of male reproductive organs via BMP/SMAD signaling pathways.

Abstract Background Robot-assisted radical prostatectomy (RARP) is commonly performed using the transperitoneal (TP) approach with six trocars over an 8-cm distance in the steep Trendelenburg position. In this study, we investigated the feasibility and the benefit of using the extraperitoneal (EP) approach with six trocars over a 4-cm distance in a flat or 5° Trendelenburg position. We also introduced four new steps to the surgical procedure and compared the surgical results and complications between the EP and TP approach using propensity score matching. Methods Between August 2012 and August 2016, 200 consecutive patients without any physical restrictions underwent RARP with the EP approach in a less than 5° Trendelenburg position, and 428 consecutive patients underwent RARP with the TP approach in a steep Trendelenburg position. Four new steps to RARP using the EP approach were developed: 1) arranging six trocars; 2) creating the EP space using laparoscopic forceps; 3) holding the separated prostate in the EP space outside the robotic view; and 4) preventing a postoperative inguinal hernia. Clinicopathological results and complications were compared between the EP and TP approaches using propensity score matching. Propensity scores were calculated for each patient using multivariate logistic regression based on the preoperative covariates. Results All 200 patients safely underwent RARP using the EP approach. The mean volume of estimated blood loss and duration of indwelling urethral catheter use were significantly lower with the EP approach than the TP approach (139.9 vs 184.9 mL, p = 0.03 and 5.6 vs 7.7 days, p

Urothelial carcinoma of the bladder in childhood is extremely rare. We report on a 12-year-old girl with urothelial carcinoma of the bladder who presented with gross hematuria. Immunohistochemical staining showed normal levels of cytokeratin 20 expression and decreased levels of Ki67 and p53 expression. Human papillomavirus, which can be a cause of urothelial carcinoma of the bladder, was not detected by polymerase chain reaction. We reviewed the literature focusing on diagnostic tools for urothelial carcinoma of the bladder and determined that abdominal ultrasonography, with an extremely high sensitivity of 98%, could be a useful tool for postoperative follow-up in childhood.

Congenital bladder diverticulum is rare and is usually observed in male children. An 8-year-old Japanese boy was referred to a hospital with fever and gross hematuria and was treated with a course of antibiotics. Because the dilatation of the ureter was suspected by abdominal ultrasonographic examination, he was referred to our hospital. We diagnosed congenital bladder diverticulum by computed tomographic scan and carried out laparoscopic bladder diverticulectomy and extravesical ureteral reimplantation. Four years later, there was no recurrence of gross hematuria or urinary tract infection. Keywords: Congenital bladder diverticulum, Laparoscopic diverticulectomy, Histology, Voiding cystourethrogram

An inflammatory myofibroblastic tumor (IMT) is a distinctive neoplasm composed of myofibroblastic and fibroblastic spindle cells, accompanied by inflammatory infiltration of plasma cells, lymphocytes, and eosinophils. IMTs rarely occur in the urinary bladder. It is important to distinguish this tumor from other malignant spindle cell tumors. Herein, we report a patient with an IMT showing muscle invasion, who underwent a transurethral resection of the bladder tumor and, at a later date, partial cystectomy. The resected tumor specimen revealed a proliferation of spindle-shaped cells on a background of plasma cells and lymphocytes. Immunohistochemical staining showed the tumor to be positive for anaplastic lymphoma kinase (ALK), smooth muscle actin, and vascular endothelial growth factor (VEGF). Such histopathological findings were indicative of an IMT, suggesting the use of inhibitors of ALK and VEGF as pharmacotherapy.

Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB) is a rare variant of infiltrating urothelial carcinoma. We report a case of LELCB in a 43-year-old man. Ultrasonography and cystoscopy revealed two bladder tumors, one on the left side of the trigone and the other on the right side of the trigone. Transurethral resection of the bladder tumors was performed and pathological analysis revealed undifferentiated carcinoma. We therefore performed radical cystectomy and urinary diversion. Immunohistochemically the tumor cells were positive for cytokeratin, but negative for Epstein-Barr virus-encoded small RNA in situ hybridization as found for previous cases of LELCB. The final pathological diagnosis was a lymphoepithelioma-like variant of urothelial carcinoma with perivesical soft tissue invasion. For adjuvant systemic chemotherapy, three courses of cisplatin were administered. The patient subsequently became free of cancer 72 months postoperatively. Based on the literature, pure or predominant LELCB types show favorable prognoses due to their sensitivity to chemotherapy or radiotherapy. An analysis of the apparent diffusion coefficient (ADC) values of bladder tumors examined in our institution revealed that the ADC value measured for this LELCB was relatively low compared to conventional urothelial carcinomas. This suggests that measuring the ADC value of a lymphoepithelioma-like carcinoma prior to operation may be helpful in predicting LELCB.

Delayed radiation myelopathy (DRM) is a rare disorder that rapidly leads to disabilities, and the median incubation period was reported to be about 2 years (from 6 months to a few years). In this report, we describe a 61-year-old woman who presented with rapid progressive numbness and weakness in both legs 22 months after palliative radiation therapy with 39 Gy in 3 Gy fractions. She was diagnosed with DRM of the thoracic vertebrae and was treated sequentially with corticosteroids, heparin, and hyperbaric oxygen therapy. However, they were not effective, and complete paralysis of the legs occurred in 3 months.

The etiology of scrotal pain is clinically classified in terms of the necessity for emergency surgery. Lately, color Doppler ultrasonography has reduced unnecessary surgeries, but there are still some cases that require immediate exploration because of an uncertain diagnosis. Here, we describe the case of a 14-month-old boy, who could not deliver his complaint accurately, presenting with a grumpy mood and a red swollen scrotum. Emergency surgery revealed that the cause was intense inflammation of the hydrocele wall, which typically does not cause acute scrotum. We also reviewed rare etiologies of scrotal pain for general physicians to develop the differential diagnosis.

Here, we report the case of a 62-year-old man with neuroblastoma, which is extremely rare in adults. His tumor was resected, but it recurred four months later. Radiotherapy reduced tumor size, and the patient remained in good health three years after surgical tumor removal. The residual tumor and the treatments administered to this patient were evaluated. We have also reviewed the literature.

A 5-month-old boy presented with right scrotal swelling. Color Doppler ultrasonography showed an encapsulated hypoechoic lesion with surrounding hyperemia in the right tail of the epididymis. We performed surgical exploration of the scrotum because it was not considered to be a typical epididymitis. During the operation, we aspirated pus from his right epididymis through a needle by referring to the color Doppler findings. This is the first case of epididymal abscess in an infant to be successfully diagnosed and treated with needle aspiration.

Phimosis is a condition in which the prepuce cannot be retracted over the glans penis. Actually, physiologic phimosis is common in male patients up to 3 years of age, but often extends into older age groups. Balanoposthitisis a common inflammation occurring in 4–11% of uncircumcised boys. Circumcision is generally undertaken for three reasons: first, as an item of religious practice, typically neonatally although occasionally transpubertally, as a rite of passage; second, as a prophylactic measure against future ailments for the reduction in the risk of penile cancer, urinary tract infection, and sexually transmitted infection; and third, for immediate medical indication. Balanitisxeroticaobliterans is an infiltrative skin condition that causes a pathological phimosis and has been considered to be the only absolute indication for circumcision. Various kinds of effective alternatives to circumcision have been described, including manual retraction therapy, topical steroid therapy, and several variations of preputioplasty. All of these treatments have the ability to retract the foreskin as their goal and do not involve the removal of the entire foreskin. Paraphimosis is a condition in which the foreskin is left retracted. When manipulation is not effective, a dorsal slit should be done, which is usually followed by circumcision.

Accessory scrotum is an unusual developmental anomaly defined as additional scrotal tissue in addition to a normally developed scrotum. The accessory scrotum arises posterior to the normally located scrotum and does not contain a testis. We report a case of an 18-month-old boy with an accessory scrotum attached to a perineal lipoma. We resected both and determined histologically that they were of the same tissue as the scrotum, including the presence of androgen receptor expression. To the best of our knowledge, this is the first case to assess androgen receptor expression in an accessory scrotum using immunostaining.

Background46,XY disorders of sex development (46,XY DSD) are genetically heterogeneous conditions. Recently, a few submicroscopic genomic rearrangements have been reported as novel genetic causes of 46,XY DSD.Methodology/principal findingsTo clarify the role of cryptic rearrangements in the development of 46,XY DSD, we performed array-based comparative genomic hybridization analysis for 24 genetic males with genital abnormalities. Heterozygous submicroscopic deletions were identified in three cases (cases 1-3). A ∼8.5 Mb terminal deletion at 9p24.1-24.3 was detected in case 1 that presented with complete female-type external genitalia and mental retardation; a ∼2.0 Mb interstitial deletion at 20p13 was identified in case 2 with ambiguous external genitalia and short stature; and a ∼18.0 Mb interstitial deletion at 2q31.1-32 was found in case 3 with ambiguous external genitalia, mental retardation and multiple anomalies. The genital abnormalities of case 1 could be ascribed to gonadal dysgenesis caused by haploinsufficiency of DMRT1, while those of case 3 were possibly associated with perturbed organogenesis due to a deletion of the HOXD cluster. The deletion in case 2 affected 36 genes, none of which have been previously implicated in sex development.Conclusions/significanceThe results indicate that cryptic genomic rearrangements constitute an important part of the molecular bases of 46,XY DSD and that submicroscopic deletions can lead to various types of 46,XY DSD that occur as components of contiguous gene deletion syndromes. Most importantly, our data provide a novel candidate locus for 46,XY DSD at 20p13.

Background/purposeWe hypothesized that polymorphic differences among individuals might cause variations in the effect that environmental endocrine disruptors (EEDs) have on male genital malformations (MGMs). In this study, individual variation in the genetic response to low-dose bisphenol A (BPA) was investigated in human foreskin fibroblast cells (hFFCs) derived from child cryptorchidism (CO) and hypospadias (HS) patients.Methodology/principal findingshFFCs were collected from control children without MGMs (n=5) and child CO and HS patients (n=8 and 21, respectively). BPA exposure (10 nM) was found to inhibit matrix metalloproteinase-11 (MMP11) expression in the HS group (0.74-fold, P=0.0034) but not in the control group (0.93-fold, P=0.84) and CO group (0.94-fold, P=0.70). Significantly lower levels of MMP11 expression were observed in the HS group compared with the control group (0.80-fold, P=0.0088) and CO group (0.79-fold, P=0.039) in response to 10 nM BPA. The effect of single-nucleotide polymorphism rs5000770 (G>A), located within the aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) locus, on individual sensitivity to low-dose BPA was investigated in the HS group. A significant difference in neurotensin receptor 1 (NTSR1) expression in response to 10 nM BPA was observed between AA and AG/GG groups (n=6 and 15, respectively. P=0.031). However, no significant difference in ARNT2 expression was observed (P=0.18).Conclusions/significanceThis study advances our understanding of the specificity of low-dose BPA effects on human reproductive health. Our results suggest that genetic variability among individuals affects susceptibility to the effects of EEDs exposure as a potential cause of HS.

The effect of low-dose bisphenol A (BPA) exposure on human reproductive health is still controversial. To better understand the molecular basis of the effect of BPA on human reproductive health, a genome-wide screen was performed using human foreskin fibroblast cells (hFFCs) derived from child hypospadias (HS) patients to identify novel targets of low-dose BPA exposure.Gene expression profiles of hFFCs were measured after exposure to 10 nM BPA, 0.01 nM 17β-estradiol (E2) or 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 24 h. Differentially expressed genes were identified using an unpaired Student's t test with P value cut off at 0.05 and fold change of more than 1.2. These genes were selected for network generation and pathway analysis using Ingenuity Pathways Analysis, Pathway Express and KegArray. Seventy-one genes (42 downregulated and 29 upregulated) were identified as significantly differentially expressed in response to BPA, among which 43 genes were found to be affected exclusively by BPA compared with E2 and TCDD. Of particular interest, real-time PCR analysis revealed that the expression of matrix metallopeptidase 11 (MMP11), a well-known effector of development and normal physiology, was found to be inhibited by BPA (0.47-fold and 0.37-fold at 10 nM and 100 nM, respectively). Furthermore, study of hFFCs derived from HS and cryptorchidism (CO) patients (n = 23 and 11, respectively) indicated that MMP11 expression was significantly lower in the HS group than in the CO group (0.25-fold, P = 0.0027).This present study suggests that an involvement of BPA in the etiology of HS might be associated with the downregulation of MMP11. Further study to elucidate the function of the novel target genes identified in this study during genital tubercle development might increase our knowledge of the effects of low-dose BPA exposure on human reproductive health.

Caudal regression syndrome (CRS) is a rare congenital vertebral anomaly, which occurs most often in combination with spinal cord malformations and morphologic dysfunctions of the lower extremities; these signs are useful for both patients and clinicians in the diagnosis of this syndrome. However, in certain cases, clinicians have failed to identify the syndrome due to the lack of apparent anomalies, resulting in the progression of renal dysfunction caused by neuropathic bladder when CRS is eventually identified. Here, we report a case of a 2-year-old girl who was referred to our hospital for vesicoureteral reflux. At examination, she presented no neurological symptoms; however, on cystourethrography and CT scanning we found that the sacral bone was absent, through which CRS was diagnosed. A urodynamic study indicated detrusor-sphincter dyssynergia, and clean intermittent catheterization was initiated. In the present report, we describe a case of CRS with no neurologic symptoms other than a neuropathic bladder. The lack of outward signs can result in delayed diagnosis. Thus, urological examinations, including a urodynamic study, might be the only clue for identifying an underlying neurologic injury involving the lower spinal cord.