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Shigeru Nakamura,1 Kazuya Tanabe,1 Taiju Hyuga,1,2 Taro Kubo,1 Satoru Inoguchi,1 Shina Kawai,1 Hideo Nakai1 1Department of Pediatric Urology, Jichi Medical University, Children’s Medical Center Tochigi, Shimotsuke, Japan; 2Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University (WMU), Wakayama, JapanCorrespondence: Shigeru NakamuraDepartment of Pediatric Urology, Jichi Medical University, Children’s Medical Center, 3311-1, Yakushiji, Shimotsuke, Tochigi 329-0498, JapanTel +81-285-44-2111Fax +81-285-44-8452Email naka251148@gmail.comPurpose: To evaluate the treatment outcomes and postoperative complications associated with the systematic multi-site hydrodistention implantation technique (SMHIT) for primary vesicoureteral reflux (VUR) and to determine its mid-term efficacy and safety.Patients and Methods: We retrospectively reviewed the data for 17 ureters from 12 consecutive children, aged ≥ 1 year, with grade II–IV reflux and a history of febrile urinary tract infections (FUTI), who underwent a single-session of SMHIT. The primary outcome was the absence of postoperative FUTI (clinical success). The secondary outcome was improvement in reflux to grade 0–I on postoperative voiding cystourethrography (radiographic success).Results: Five and 7 children had bilateral and unilateral reflux, respectively. Reflux was categorized as grade II, III, and IV reflux in 2, 12, and 3 ureters, respectively. Seven of 10 (70%) toilet-trained children had bladder-bowel dysfunction (BBD) preoperatively. The SMHIT was performed for all patients, after which BBD improved. The mean postoperative follow-up period was 6 years and 9 months. The clinical success rate was 100%. Radiographic success was achieved in 16/17 ureters (94%) at 3– 4 months, 17/17 (100%) ureters at 1 year, and 17/17 (100%) ureters at 3 years postoperatively. Major complications did not develop postoperatively.Conclusion: When prioritizing treatment of concomitant BBD in children with primary VUR and avoiding dextranomer/hyaluronic acid injection therapy in contraindicated children according to the Food and Drug Administration recommendations, a single-session of SMHIT may be as effective and safe in the mid-term as performing open anti-reflux surgery.Keywords: dextranomer hyaluronic acid, Dx/HA, endoscopic treatment, vesicoureteral reflux

The article comments on the study "Long-Term Outcome of Low Scrotal Approach Orchiopexy without Ligation of the Processus Vaginalis" by T. Hyuga and others.

Introduction: This report describes a case with an ectopic ejaculatory duct opening into the bladder trigone in Zinner syndrome, congenital unilateral renal agenesis, and an ipsilateral seminal vesicle cyst., Case Presentation: The patient was identified when no left kidney was detected in the fetal period. Abdominal ultrasonography and pelvic plain MRI at 6 months old revealed a 10-mm cystic lesion on the dorsal aspect of the bladder. Cysto-urethroscopy at 1 year old revealed a rather short posterior urethra and right and left inferior crests extending from the posterior urethra beyond the bladder neck. The ejaculatory duct opening was identified on the bladder trigone., Conclusion: Anatomical abnormality of the ejaculatory duct may represent a cause of infertility and ejaculatory dysfunction in Zinner syndrome. Endoscopic evaluation should be performed for this rare anomaly, even in children., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

The post-surgical fluid leakage from the tubular tissues is a critical symptom after gastrointestinal or urinary tract surgeries. Elucidating the mechanism for such abnormalities is vital in surgical and medical science. The exposure of the fluid such as peritonitis due to urinary or gastrointestinal perforation has been reported to induce severe inflammation to the surrounding tissue. However, there have been no reports for the tissue responses by fluid extravasation and assessment of post-surgical and injury complication processes is therefore vital. The current model mouse study aims to investigate the effect of the urinary extravasation of the urethral injuries. Analyses on the urinary extravasation affecting both urethral mesenchyme and epithelium and the resultant spongio-fibrosis/urethral stricture were performed. The urine was injected from the lumen of urethra exposing the surrounding mesenchyme after the injury. The wound healing responses with urinary extravasation were shown as severe edematous mesenchymal lesions with the narrow urethral lumen. The epithelial cell proliferation was significantly increased in the wide layers. The mesenchymal spongio-fibrosis was induced by urethral injury with subsequent extravasation. The current report thus offers a novel research tool for surgical sciences on the urinary tract., (© 2023. The Author(s).)

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., (© 2023 Wiley Periodicals LLC.)

Erection is an essential process which requires the male penis for copulation. This copulatory process depends on the vascular dynamic regulation of the penis. The corpus cavernosum (CC) in the upper (dorsal) part of the penis plays a major role in regulating blood flow inside the penis. When the CC is filled with blood, the sinusoids, including micro-vessels, dilate during erection. The CC is an androgen-dependent organ, and various genital abnormalities including erectile dysfunction (ED) are widely known. Previous studies have shown that androgen deprivation by castration results in significantly decreased smooth muscles of the CC. Experimental works in erectile biology have previously measured intracavernosal penile pressure and mechanical tension. Such reports analyze limited features without assessing the dynamic aspects of the erectile process. In the current study, we established a novel explant system enabling direct visual imaging of the sinusoidal lumen to evaluate the dynamic movement of the cavernous space. To analyze the alternation of sinusoidal spaces, micro-dissected CC explants by patent blue dye injection were incubated and examined for their structural alternations during relaxation/contraction. The dynamic process of relaxation/contraction was analyzed with various external factors administered to the CC. The system enabled the imaging of relaxation/contraction of the lumens of the sinusoids and the collagen-containing tissues. Histological analysis on the explant system also showed the relaxation/contraction. Thus, the system mimics the regulatory process of dynamic relaxation/contraction in the erectile response. The current system also enabled evaluating the erectile pathophysiology. In the current study, the lumen of sinusoids relaxed/contracted in castrated mice similarly with normal mice. These results suggested that the dynamic erectile relaxation/contraction process was similarly retained in castrated mice. However, the system also revealed decreased duration time of erection in castrated mice. The current study is expected to promote further understanding of the pathophysiology of ED, which will be useful for new treatments in the future. Hence, the current system provides unique information to investigate the novel regulations of erectile function, which can provide tools for analyzing the pathology of ED., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fujimoto, Hashimoto, Kashimada, Kumegawa, Ueda, Hyuga, Hirashima, Inoue, Suzuki, Hara, Asamura and Yamada.)

Purpose: Penile research is expected to reveal new targets for treatment and prevention of the complex mechanisms of its disorder including erectile dysfunction (ED). Thus, analyses of the molecular processes of penile ED and continuous erection as priapism are essential issues of reproductive medicine., Methods: By performing mouse N-ethyl-N-nitrosourea mutagenesis and exome sequencing, we established a novel mouse line displaying protruded genitalia phenotype (PGP; priapism-like phenotype) and identified a novel Pitpna gene mutation for PGP. Extensive histological analyses on the Pitpna mutant and intracavernous pressure measurement (ICP) and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS)/MS analyses were performed., Results: We evaluated the role of phospholipids during erection for the first time and showed the mutants of inducible phenotypes of priapism. Moreover, quantitative analysis using LC-ESI/MS/MS revealed that the level of phosphatidylinositol (PI) was significantly lower in the mutant penile samples. These results imply that PI may contribute to penile erection by PITPα., Conclusions: Our findings suggest that the current mutant is a mouse model for priapism and abnormalities in PI signaling pathways through PITPα may lead to priapism providing an attractive novel therapeutic target in its treatment., Competing Interests: Daiki Hashimoto, Kota Fujimoto, Shin Morioka, Shinya Ayabe, Tomoya Kataoka, Ryutaro Fukumura, Yuko Ueda, Mizuki Kajimoto, Taiju Hyuga, Kentaro Suzuki, Isao Hara, Shinichi Asamura, Shigeharu Wakana, Atsushi Yoshiki, Yoichi Gondo, MasaruTamura, Takehiko Sasaki, and Gen Yamada declare that they have no conflict of interest., (© 2022 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

The murine penile erectile tissues including corpus cavernosum (CC) are composed of blood vessels, smooth muscle, and connective tissue, showing marked sexual differences. It has been known that the androgens are required for sexually dimorphic organogenesis. It is however unknown about the features of androgen signaling during mouse CC development. It is also unclear how androgen-driven downstream factors are involved such processes. In the current study, we analyzed the onset of sexually dimorphic CC formation based on histological analyses, the dynamics of androgen receptor (AR) expression, and regulation of cell proliferation. Of note, we identified Dickkopf-related protein 2 (Dkk2), an inhibitor of β-catenin signaling, was predominantly expressed in female CC compared with male. Furthermore, administration of androgens resulted in activation of β-catenin signaling. We have found the Sox9 gene, one of the essential markers for chondrocyte, was specifically expressed in the developing CC. Hence, we utilized CC-specific, Sox9 CreERT2 , β-catenin conditional mutant mice. Such mutant mice showed defective cell proliferation. Furthermore, introduction of activated form of β-catenin mutation (gain of function mutation for Wnt/β-catenin signaling) in CC induced augmented cell proliferation. Altogether, we revealed androgen-Wnt/β-catenin signal dependent cell proliferation was essential for sexually dimorphic CC formation. These findings open new avenues for understanding developmental mechanisms of androgen-dependent cell proliferation during sexual differentiation., (© 2022 Japanese Teratology Society.)

Introduction: This study aimed to clarify the advantage of retroperitoneoscopy-assisted dismembered pyeloplasty with single-site plus one port (RPSPO) for pediatric congenital hydronephrosis in patients aged ≥7 years., Methods: We retrospectively compared a group of patients aged ≥7 years (study group) with patients aged <7 years (comparison group), who underwent RPSPO between August 2015 and August 2018, in terms of preoperative patient characteristics, intra- and perioperative results, and postoperative results., Results: The study group consisted of eight patients. The median body weight at surgery was 27 kg (20-38 kg). The median age at surgery was 102.5 m (87-139 m). The severity of hydronephrosis on the affected side graded by the Society for Fetal Urology grade was grade 3 in one case and grade 2 or less in all other cases. All patients underwent a 99m Tc-MAG3 renogram. Comparison between the two groups showed significant differences in body weight at surgery (p = 0.003), age (p < 0.001), and preoperative hydronephrosis grade (p = 0.007), but the median length of the skin incision was 20 mm in both groups, with no significant difference (p = 1.000). Redo pyeloplasty was not required in any patient in either group., Conclusion: RPSPO is an advantageous procedure for older children because it allows precise ureteropelvic neoanastomosis under direct vision and the same wound size as in younger children., (© 2022 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: Head and neck reconstructions using the pectoralis major myocutaneous pedicle flap (PMMF) with thoracoacromial artery alone are prone to hemodynamic instability, possibly leading to infection, prolapse, hematoma, seroma, and partial or total flap failure (6%-71%). Aside from unstable blood circulation, reported risk factors for these complications include feminine gender, smoking, and having diabetes mellitus. Preservation of the lateral thoracic artery in addition to the thoracoacromial artery has been suggested as a way to improve unstable blood circulation in the PMMF., Methods: This is a single-center, prospective, uncontrolled case series. Circulation to the PMMF was studied intraoperatively with and without lateral thoracic artery clamping after harvest. Indocyanine green (ICG) angiopathy, a quantitative hemodynamic assessment method, was used to analyze three parameters: maximum intensity (Imax), time from start of ICG to maximum intensity (Tmax), and slope of intensity (Smax = Imax/Tmax). Hemodynamic parameters, such as pulse rate and blood pressure, were all within normal ranges. Allergy to contrast media was criterion for exclusion., Results: Six patients all had oral cancer as their primary disease. Their background was characterized by established risk factors: four patients had a history of smoking, two had diabetes mellitus, and two were women. Postoperatively, no patients had complications at the recipient or donor sites. Mean results of the analysis were Imax: 60 ± 47, Tmax: 91 ± 55, Smax: 0.8 ± 0.5 in the clamped group and Imax: 85 ± 40, Tmax: 73 ± 42, Smax: 1.8 ± 1.5 in the un-clamped group. Significant difference was observed in Imax ( P = 0.03) and Smax ( P = 0.03)., Conclusion: Lateral thoracic artery preservation appears to be useful for stabilizing blood circulation to the PMMF, including in patients considered to be at high-risk for complications, such as women, smokers, and patients with diabetes mellitus., Competing Interests: Disclosure: The authors have no financial interest to declare in relation to the content of this article. This study was supported by funds from institutional sources only., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The thymus facilitates mature T cell production by providing a suitable stromal microenvironment. This microenvironment is impaired by radiation and aging which lead to immune system disturbances known as thymic involution. Young adult thymus shows thymic recovery after such involution. Although various genes have been reported for thymocytes and thymic epithelial cells in such processes, the roles of stromal transcription factors in these remain incompletely understood. MafB (v-maf musculoaponeurotic fibrosarcoma oncogene homolog B) is a transcription factor expressed in thymic stroma and its expression was induced a day after radiation exposure. Hence, the roles of mesenchymal MafB in the process of thymic regeneration offers an intriguing research topic also for radiation biology. The current study investigated whether MafB plays roles in the adult thymus. MafB/green fluorescent protein knock-in mutant (MafB +/GFP ) mice showed impaired thymic regeneration after the sublethal irradiation, judged by reduced thymus size, total thymocyte number and medullary complexity. Furthermore, IL4 was induced after irradiation and such induction was reduced in mutant mice. The mutants also displayed signs of accelerated age-related thymic involution. Altogether, these results suggest possible functions of MafB in the processes of thymic recovery after irradiation, and maintenance during aging.

Male penis is required to become erect during copulation. In the upper (dorsal) part of penis, the erectile tissue termed corpus cavernosum (CC) plays fundamental roles for erection by regulating the inner blood flow. When blood flows into the CC, the microvascular complex termed sinusoidal space is reported to expand during erection. A novel in vitro explant system to analyze the dynamic erectile responses during contraction/relaxation is established. The current data show regulatory contraction/relaxation processes induced by phenylephrine (PE) and nitric oxide (NO) donor mimicking dynamic erectile responses by in vitro CC explants. Two-photon excitation microscopy (TPEM) observation shows the synchronous movement of sinusoidal space and the entire CC. By taking advantages of the CC explant system, tadalafil (Cialis) was shown to increase sinusoidal relaxation. Histopathological changes have been generally reported associating with erection in several pathological conditions. Various stressed statuses have been suggested to occur in the erectile responses by previous studies. The current CC explant model enables to analyze such conditions through directly manipulating CC in the repeated contraction/relaxation processes. Expression of oxidative stress marker and contraction-related genes, Hypoxia-inducible factor 1-alpha (Hif1a), glutathione peroxidase 1 (Gpx1), Ras homolog family member A (RhoA), and Rho-associated protein kinase (Rock), was significantly increased in such repeated contraction/relaxation. Altogether, it is suggested that the system is valuable for analyzing structural changes and physiological responses to several regulators in the field of penile medicine., (© The Author(s) 2021. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Erectile dysfunction (ED) is one of the increasing diseases with aging society. The basis of ED derived from local penile abnormality is poorly understood because of the complex three-dimensional (3D) distribution of sinusoids in corpus cavernosum (CC). Understanding the 3D histological structure of penis is thus necessary. Analyses on the status of regulatory signals for such abnormality are also performed., Methods: To analyze the 3D structure of sinusoid, 3D reconstruction from serial sections of murine CC were performed. Histological analyses between young (2 months old) and aged (14 months old) CC were performed. As for chondrogenic signaling status of aged CC, SOX9 and RBPJK staining was examined., Results: Sinusoids prominently developed in the outer regions of CC adjacent to tunica albuginea. Aged CC samples contained ectopic chondrocytes in such regions. Associating with the appearance of chondrocytes, the expression of SOX9, chondrogenic regulator, was upregulated. The expression of RBPJK, one of the Notch signal regulators, was downregulated in the aged CC., Conclusions: Prominent sinusoids distribute in the outer region of CC which may possess important roles for erection. A possibility of ectopic chondrogenesis induced by alteration of SOX9/Notch signaling with aging is indicated., Competing Interests: Conflict of interest: Daiki Hashimoto, Mizuki Kajimoto, Yuko Ueda, Taiju Hyuga, Kota Fujimoto, Saaya Inoue, Kentaro Suzuki, Tomoya Kataoka, Kazunori Kimura, and Gen Yamada declare that they have no conflict of interest. Human rights statements and informed consent: This work does not contain human subjects. Animal studies and Approval by Ethics Committee: All institutional and national guidelines for the care and use of laboratory animals were followed. All procedures and protocols were approved by the committee on animal research at Wakayama Medical University, Wakayama, Japan (approval number: 867)., (© 2021 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Visualization of the surgically operated tissues is vital to improve surgical model animals including mouse. Urological surgeries for urethra include series of fine manipulations to treat the increasing number of birth defects such as hypospadias. Hence visualization of the urethral status is vital. Inappropriate urethral surgical procedure often leads to the incomplete wound healing and subsequent formation of urethro-cutaneous fistula or urethral stricture. Application of indocyanine green mediated visualization of the urethra was first performed in the current study. Indocyanine green revealed the bladder but not the urethral status in mouse. Antegrade injection of contrast agent into the bladder enabled to detect the urethral status in vivo. The visualization of the leakage of contrast agent from the operated region was shown as the state of urethral fistula in the current hypospadias mouse model and urethral stricture was also revealed. A second trial for contrast agent was performed after the initial operation and a tendency of accelerated urethral stricture was observed. Thus, assessment of post-surgical conditions of urogenital tissues can be improved by the current analyses on the urethral status.

Objective: To determine the long-term safety and efficacy of ureteric reimplantation with psoas bladder hitch (PBH) in patients aged <12 months with unilateral obstructive megaureter (OM)., Patients and Methods: We retrospectively compared a group of patients aged <12 months (study group) with an group of patients aged ≥12 months (comparison group), who underwent PBH for OM between September 2007 and April 2017, in terms of preoperative patient characteristics, intra- and peri-operative results, and postoperative results., Results: The study group comprised seven infants, five boys and two girls. The median (range) age at the time of PBH was 3 (2-8) months; OM was detected by ultrasonography during the fetal period. The left side was affected in four infants and the right side in three. Four infants had primary OM (POM). In all three infants who had ectopic OM in the complete double renal pelvis and ureter, the OM involved the ureter from the upper half of the kidney. The median (range) follow-up period after PBH was 45 (33-129) months. Comparison of the two groups showed no significant difference in terms of surgical time (P = 0.948) and length of hospital stay (P = 0.125). In both groups, hydroureteronephrosis improved postoperatively in all patients. There was no significant difference between the two groups in terms of postoperative complications, such as vesico-ureteric reflux, febrile urinary tract infection and deterioration of ipsilateral renal function. Notably, no patient underwent reoperation in either group., Conclusion: Psoas bladder hitch for unilateral OM including POM appears to be safe and effective in the long term for patients aged <12 months and for those aged ≥12 months. Although not routinely recommended, PBH appears to be a viable option for selected infants with POM., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Hedgehog (Hh) signaling is an essential growth factor signaling pathway especially in the regulation of epithelial-mesenchymal interactions (EMI) during the development of the urogenital organs such as the bladder and the external genitalia (EXG). The Hh ligands are often expressed in the epithelia, affecting the surrounding mesenchyme, and thus constituting a form of paracrine signaling. The development of the urogenital organ, therefore, provides an intriguing opportunity to study EMI and its relationship with other pathways, such as hormonal signaling. Cellular interactions of prostate cancer (PCa) with its neighboring tissue is also noteworthy. The local microenvironment, including the bone metastatic site, can release cellular signals which can affect the malignant tumors, and vice versa. Thus, it is necessary to compare possible similarities and divergences in Hh signaling functions and its interaction with other local growth factors, such as BMP (bone morphogenetic protein) between organogenesis and tumorigenesis. Additionally, this review will discuss two pertinent research aspects of Hh signaling: (1) the potential signaling crosstalk between Hh and androgen signaling; and (2) the effect of signaling between the epithelia and the mesenchyme on the status of the basement membrane with extracellular matrix structures located on the epithelial-mesenchymal interface.

Background: A voided volume (VV) of <50% of the expected bladder capacity for age is considered small VV. It was recommended that a VV ≥50% of expected bladder capacity for age is required to assess uroflowmetry (UFM) curves because a small VV causes changes in UFM curve characteristics. However, no clear consensus has been reached on the criterion for evaluating UFM curve patterns., Objective: The aim of the study was to evaluate the reproducibility and characteristics of UFM curve patterns in children with daytime urinary incontinence (DUI) and with a variety of VVs., Methods: This study investigated 119 children (79 boys and 40 girls) with primary DUI who underwent UFM 3 times on the same day and were classified into two groups: small VV (<50% of expected bladder capacity for age) in 0-1 of the 3 UFM measurements (group 1; normal VV) or in 2-3 of the 3 UFM measurements (group 2; small VV). The authors then evaluated the agreement of UFM curve patterns among the 3 measurements, classifying complete, partial, or no agreement according to the number of identical curve patterns. The authors also evaluated the most characteristic patterns of UFM curve patterns for each group., Results: Group 1 comprised 45 children, and group 2 comprised 74 children. Rates of complete agreement (group 1, 24/45; group 2, 30/74), partial agreement (group 1, 19/45; group 2, 35/74), and no agreement (group 1, 2/45; group 2, 9/74) did not differ significantly between groups (p = 0.226). Bell curve patterns were significantly more common in group 1 than in group 2 (p = 0.025). Frequency of the tower pattern was significantly higher in group 2 than in group 1 (p = 0.006) (Summary table)., Discussion: No differences in agreement rates of UFM curve patterns were seen between two groups (small and normal VV). The authors thus suggest that UFM curve patterns can be validly assessed in children with DUI and with small VV. It was found that the bell pattern was significantly more common among children with normal VV, whereas the tower pattern was significantly more common among children with small VV. The tower pattern reflects an overactive bladder. The present results suggest that some children have DUI that is not attributable to urgency., Conclusion: Reproducibility of UFM curve patterns might be properly assessed even in children with DUI and with small VV. This result suggests the presence of various pathological conditions other than the conditions with urgency underlying DUI., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Development of external genitalia (ExG) has been a topic of long mystery in the field of organogenesis research. Early stage male and female of mouse embryos develop a common genital tubercle (GT) in the perineum whose outgrowth extends distally from the posterior cloacal regions. Concomitant with GT outgrowth, the cloaca is divided into urogenital sinus and anorectum by urorectal septum (URS) internally. The outgrowth of the GT is associated with the formation of endodermal epithelial urethral plate (UP) attached to the ventral epidermis of the GT. Such a common developmental phase is observed until around embryonic day 15.5 (E15.5) morphologically in mouse embryogenesis. Various growth factor genes, such as Fibroblast growth factor (Fgf) and Wnt genes are expressed and function during GT formation. Since the discovery of key growth factor signals and several regulatory molecules, elucidation of their functions has been achieved utilizing mouse developmental models, conditional gene knockout mouse and in vitro culture. Analyses on the phenotypes of such mouse models have revealed that several growth factor families play fundamental roles in ExG organogenesis based on the epithelial-mesenchymal interaction (EMI). More recently, EMI between developing urethral epithelia and its bilateral mesenchyme of later stages is also reported during subsequent stage of androgen-dependent male-type urethral formation in the mouse embryo. Mafb, belonging to AP-1 family and a key androgen-responsive mesenchymal gene, is identified and starts to be expressed around E14.5 when masculinization of the urethra is initiated. Mesenchymal cell condensation and migration, which are regulated by nonmuscle myosin, are shown to be essential process for masculinization. Hence, studies on EMI at various embryonic stages are important not only for early but also for subsequent masculinization of the urethra. In this review, a dynamic mode of EMI for both early and late phases of ExG development is discussed., (Copyright © 2019 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Aim: To evaluate the uroflowmetry (UFM), which reflects the urinary symptoms of children with nocturnal enuresis (NE)., Methods: This study retrospectively investigated 93 children who underwent UFM three times on the same day (≥8 years old; mean age: 9 years and 10 months; 66 boys and 27 girls). Children with the combination of daytime incontinence (DI) and NE (DI+NE group: n = 45) and NE alone (isolated NE group: n = 48) were compared. UFM curve patterns were classified into five types: bell (B), tower (T), staccato (S), plateau (P), and interrupted (I). An unclassified (U) curve pattern was designated when all three curve patterns differed. Patterns other than the B pattern were considered abnormal (A). Each score in the dysfunctional voiding symptom score (DVSS) was also compared between the two groups., Results: The UFM curve pattern was B (n = 21), T (n = 15), S (n = 4), P (n = 1), U (n = 4) in the DI+NE group and B (n = 25), T (n = 10), S (n = 7), P (n = 2), U (n = 4) in the isolated NE group, indicating no significant difference (B vs A; P = .680). The two items of DVSS questionnaire were significantly greater in the DI+NE group than in the isolated NE group (voiding postponement: 0.93 ± 1.18 vs 0.23 ± 0.56, P = .001, urgency: 2.09 ± 1.06 vs 0.56 ± 0.85, P < .001)., Conclusion: The abnormal UFM curve patterns did not differ significantly between NE children with and without DI. However, the DVSS questionnaire scores differed significantly. UFM did not reflect the urinary symptoms of children with NE., (© 2019 Wiley Periodicals, Inc.)

Background: We previously reported that the top-down approach (TDA) for infants with febrile urinary tract infections (fUTI) could prevent recurrent fUTI (r-fUTI) but produced a high number of false-positives on acute-phase 99m Tc dimercaptosuccinic acid (DMSA) renal scintigraphy. Therefore we compared the ultrasonography-oriented approach (USOA) with TDA from the viewpoint of prevention of r-fUTI., Methods: The TDA was applied between July 2010 and February 2014 and the USOA was applied between March 2014 and April 2017 in infants with first fUTI. In the USOA group, voiding cystourethrography (VCUG) was performed in the case of abnormality on acute-phase renal bladder ultrasonography (RBUS) or on chronic- phase DMSA, which were performed in all cases. The frequency of r-fUTI was compared between the TDA group and USOA group retrospectively., Results: Seventy-four infants (52 male) and 79 infants (60 male) received TDA or USOA, respectively. No significant differences were found between the TDA and USOA groups in male : female ratio, age in months at initial onset of fUTI, observation period, or number of cases of r-fUTI (TDA group, n = 4; USOA group, n = 5). Seventy-four DMSA scintigraphy and 25 VCUG were carried out in the USOA group, and 111 DMSA scintigraphy and 34 VCUG in the TDA group., Conclusions: Both USOA and TDA were valid for prevention of r-fUTI, but USOA was superior to TDA with regard to the reduced number of patients undergoing VCUG and DMSA., (© 2019 Japan Pediatric Society.)

Development of external genitalia and perineum is the subject of developmental biology as well as toxicology and teratology researches. Cloaca forms in the lower (caudal) end of endoderm. Such endodermal epithelia and surrounding mesenchyme interact with various signals to form the external genitalia. External genitalia (the anlage termed as genital tubercle: GT) formation shows prominent sexually dimorphic morphogenesis in late embryonic stages, which is an unexplored developmental research field because of many reasons. External genitalia develop adjacent to the cloaca which develops urethra and corporal bodies. Developmental regulators including growth factor signals are necessary for epithelia-mesenchyme interaction (EMI) in posterior embryos including the cloaca and urethra in the genitalia. In the case of male type urethra, formation of tubular urethra proceeds from the lower (ventral) side of external genitalia as a masculinization process in contrast to the case of female urethra. Mechanisms for its development are not elucidated yet due to the lack of suitable mutant mouse models. Because of the recent progresses of Cre (recombinase)-mediated conditional target gene modification analyses, many developmental regulatory genes become increasingly analyzed. Conditional gene knockout mouse approaches and tissue lineage approaches are expected to offer vital information for such sexually dimorphic developmental processes. This review aims to offer recent updates on the progresses of these emerging developmental processes for the research field of congenital anomalies., (© 2018 Japanese Teratology Society.)

Objective: To correct all types of glanular/subcoronal hypospadias, we performed surgery named the distal urethroplasty and glanuloplasty procedure (DUG procedure). We analyzed cases that we have experienced., Methods: A vertical incision with the meatal margin was made in the 12 o'clock direction, with the margin of the external urethral meatus as the center. By this meatoplasty according to Heineke-Mikulicz principle, we changed all type of glanular/subcoronal hypospadias to the hypospadias with wide meatus and wide glans. And then Thiersh-Duplay procedure was performed., Results: Consecutive 24 underwent modified DUG procedure. The mean age at the time of surgery was 19.0 ± 11.9 months and the mean preoperative glans width was 13 ± 1.5 mm. The external urethral meatus was located glanular in 13 and subcoronal in 11. Hypoplastic urethra (HU) was observed in 7. Skin chordee in 10, penile torsion in 6 and meatal stenosis in 10 were observed. The mean surgical duration was 106 ± 25.4 minutes and the mean postoperative observation period was 40.5 ± 26.2 months. All patients with preoperative skin chordee, penile torsion, and meatal stenosis were improved postoperatively, and in all cases, apart from the patient with meatal regression with longest HU from glanular to distal penile, the slit-like shape of the external urethral meatus was achieved., Conclusion: DUG procedure can be used for any type of glanular/subcoronal hypospadias but care should be taken not to indicate too aggressively for glanular/subcoronal hypospadias accompanying long HU to distal penile shaft., (Copyright © 2018. Published by Elsevier Inc.)

A 9-year-old girl was diagnosed with primary alveolar soft part sarcoma of the bladder after imaging examinations and transurethral resection (TUR) of the bladder tumor. As a positive surgical margin of the TUR indicated residual tumor cells, we performed a cystourethrectomy to remove the tumor. A continent urinary reservoir for self-catheterization was constructed using the Mainz pouch technique, and an abdominal (umbilical) continent catheterizable stoma using the appendix was performed. For 2.5 years postoperatively, the patient remained free of local recurrence and distant metastasis. The patient's clinical course has been favorable, with good management of clean intermittent self-catheterization.

Purpose: Endoscopic transurethral incision (TUI) of posterior urethral valve (PUV) can improve daytime urinary incontinence (DUI) and nocturnal enuresis (NE). However, the underlying mechanism has not been elucidated. In this study, we retrospectively examined the mobility of the urethra before and after TUI by measuring the urethral angle with voiding cystourethrography (VCUG), to clarify the effects of TUI on the morphology of the urethra during voiding., Methods: Between July 2010 and December 2014, 29 boys with intractable DUI and/or NE were diagnosed as PUV and underwent endoscopic TUI. VCUG during voiding phase was performed at sequential radiographic spot images (1 image per second) at a 45° angle in oblique standing position. The point at which the angle of the urethra was the smallest during urination was regarded as the minimum urethral angle. The maximum urethral angle during early voiding phase was compared with the minimum urethral angle, and the percentage by which this angle changed was calculated as the flexion rate. Then changes in minimum urethral angle and flexion rate were analyzed before and 3-4 months after TUI., Results: After TUI, the minimum urethral angle on VCUG became more obtuse (before vs. after TUI, respectively: 112.7 vs. 124.5°, p < 0.001), the flexion rate decreased (before vs. after TUI, respectively: 11.8 vs. 4.1%, p < 0.001)., Conclusions: This study demonstrated a significant difference in the degree of change. The findings may contribute to understanding of the mechanism of improvement in symptoms after TUI in patients with PUV.

Objective: To evaluate the effectiveness of a 3-month enuresis alarm (EA) treatment and repeat EA treatment among pediatric patients with nocturnal enuresis, and to compare patient characteristics among "responders" and "nonresponders" to treatment., Materials and Methods: Clinical outcomes were retrospectively evaluated for 137 children (94 boys and 43 girls, mean age, 10.1 years). Effectiveness was evaluated after an initial 3-month treatment, using the International Children's Continence Society criteria. Among children in the no-response group at 3 months, those who continued the EA treatment for ≥4 months were subclassified into group 1, whereas children who repeated the EA treatment at an interval ≥6 months were subclassified into group 2., Results: Among our 137 cases, 19 achieved complete response and 47 achieved partial response at 3 months, for an overall treatment effectiveness rate of 48%. Among the no-response group, treatment was extended in 17 cases (group 1), with 3 (18%) achieving a successful outcome. Treatment was repeated in 18 cases (group 2). In group 2, 8 (44%) achieved successful outcome at 3-month time point. Daytime urinary incontinence did not modify treatment effectiveness., Conclusion: EA treatment should be given for a short period of time and should not be continued without a definite purpose or clear response. Suspending and then repeating this treatment after an appropriate interval is effective for patients who do not respond to the initial course of treatment., (Copyright © 2017. Published by Elsevier Inc.)

Background: Acute-phase technetium-99 m dimercaptosuccinic acid (DMSA) scintigraphy is recommended for initial imaging in children with febrile urinary tract infection (fUTI). Recently, the importance of identifying patients at risk of recurrent fUTI (r-fUTI) has been emphasized. To clarify the effectiveness of DMSA scintigraphy for predicting r-fUTI in infants, we investigated the relationship between defects on DMSA scintigraphy and r-fUTI., Methods: Seventy-nine consecutive infants (male: female, 60:19) with fUTI were enrolled in this study. DMSA scintigraphy was performed in the acute phase, and patients with defect underwent voiding cystourethrography and chronic-phase (6 months later) DMSA scintigraphy. Patients were followed on continuous antibiotic prophylaxis (CAP)., Results: Defects on acute-phase DMSA scintigraphy were observed in 32 children (40.5%) of 79. The mean follow-up observation period was 17.0 ± 10.1 months. Four patients had r-fUTI (5%). Two of them had defects on DMSA scintigraphy in both the acute phase and chronic phase, and had bilateral vesicoureteral reflux (VUR) grade IV. Two others had r-fUTI without defects on DMSA and did not have VUR. Twelve patients had defect on chronic-phase DMSA scintigraphy and four of them had no VUR., Conclusions: The top-down approach is a possible method for predicting r-fUTI in infants and does not miss clinically significant VUR. Also, given that the prevalence of r-fUTI was 5% regardless of the presence of defects on acute-phase DMSA, then, in conjunction with genital hygiene and CAP, acute-phase DMSA might be unnecessary if chronic-phase DMSA is performed for all patients to detect renal scar., (© 2017 Japan Pediatric Society.)

Vesicoureteral reflux (VUR) is one of the most common diseases in pediatric urology and classified into primary and secondary VUR. Although posterior urethral valve (PUV) is well known as a cause of the secondary VUR, it is controversial that minor urethral deformity recognized in voiding cystourethrography represents mild end of PUV spectrum and contributes to the secondary VUR. We have been studying for these ten years congenital urethral obstructive lesions with special attention to its urethrographic and endoscopic morphology as well as therapeutic response with transurethral incision. Our conclusion to date is that congenital obstructive lesion in the postero-membranous urethra is exclusively PUV (types 1 and 3) and that severity of obstruction depends on broad spectrum of morphological features recognized in PUV. Endoscopic diagnostic criteria for PUV are being consolidated., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Background: Renal dysplasia is the most important cause of end-stage renal disease in children. The histopathological characteristic of dysplasia is primitive tubules with fibromuscular disorganization. Renal dysplasia often includes metaplastic cartilage. Metaplastic cartilage in renal dysplasia has been explained as occurring secondary to vesicoureteral reflux (VUR). Additionally, renal dysplasia is observed in renal dysplasia-associated syndromes, which are combinations of multiple developmental malformations and include VACTERL association., Case Presentation: We observed the following multiple developmental malformations in a 108-day-old male infant during a nephrectomy: a nonfunctioning right kidney with VUR, hemidiaphragmatic eventration, a ventricular septal defect (VSD) with tetralogy of Fallot in the heart, cryptorchidism, and hyperdactylia. These developmental anomalies satisfied the diagnostic criteria for VACTERL association. A surgical specimen of the right nonfunctioning kidney revealed prominent cartilaginous metaplasia in the renal dysplasia with VUR. The densities of the ectopic cartilaginous lesions in this nonfunctioning kidney were extraordinarily high compared with other renal dysplasia cases. Giemsa banding of his genome produced normal results. The patient has not undergone further detailed genomic investigation., Conclusion: This case might be a novel type of VACTERL association, that is, renal dysplasia combined with prominent cartilaginous metaplasia, tetralogy of Fallot and VSD of the heart, hemidiaphragmatic eventration, and hyperdactylia.

Purpose This study aims to evaluate the endoscopic morphological features of congenital posterior urethral obstructions in boys with refractory daytime urinary incontinence and/or nocturnal enuresis. Patients and Methods A total of 54 consecutive patients underwent endoscopy and were diagnosed with a posterior urethral valve (PUV) (types 1-4). PUV type 1 was classified as severe, moderate, or mild. A transurethral incision (TUI) was mainly performed for anterior wall lesions of the PUV. Voiding cystourethrography and pressure flow studies (PFS) were performed before and 3 to 4 months after TUI. Clinical symptoms were evaluated 6 months after TUI, and outcomes were assessed according to PFS waveform pattern groups (synergic pattern [SP] and dyssynergic pattern [DP]). Results All patients had PUV type 1 and/or 3 (i.e., n = 34 type 1, 7 type 3, and 13 types 1 and 3). There were severe (n = 1), moderate (n = 21), and mild (n = 25) cases of PUV type 1. According to PFS, SP and DP were present in 43 and 11 patients, respectively. TUI was effective in the SP group and symptoms improved in 77.4 and 69.3% of patients with daytime incontinence and nocturnal enuresis, respectively. Almost no effect was observed in the DP group. A significant decrease in the detrusor pressure was observed at maximum flow rate using PFS in the SP group. Conclusions PUV type 1 encompassed lesions with a spectrum of obstructions ranging from severe to mild, with mild types whose main obstructive lesion existed at the anterior wall of urethra occurring most frequently in boys with refractory daytime urinary incontinence and/or nocturnal enuresis., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: We performed low scrotal approach orchiopexy in patients with prescrotal cryptorchidism. The processus vaginalis was not ligated if it was not widely patent. We retrospectively evaluated the long-term outcomes of low scrotal approach orchiopexy without processus vaginalis ligation., Materials and Methods: A total of 137 patients (227 testes) were diagnosed with prescrotal cryptorchidism between October 2009 and April 2014. All patients underwent low scrotal approach orchiopexy. Mean age at surgery was 34.9 months. The processus vaginalis was deemed to be not widely patent when a sound could not be passed into the abdominal cavity through the internal inguinal ring, and the processus vaginalis was not ligated in such cases., Results: Intraoperative findings revealed that the processus vaginalis was widely patent in 10 testes and was not widely patent in 217. A widely patent processus vaginalis was closed via scrotal approach in 5 testes, while an inguinal approach was necessary in 5. Median followup was 44 months (range 20 to 73). Postoperative complications included reascending testis in 1 case where an inguinal approach was necessary. No patient manifested testicular atrophy or inguinal hernia., Conclusions: Low scrotal approach orchiopexy is a useful and safe procedure for treating patients with prescrotal cryptorchidism. Ligation is unnecessary when the processus vaginalis is not widely patent., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We evaluated the long-term outcome of the Pippi Salle procedure in patients with severe intrinsic urethral sphincter deficiency., Materials and Methods: We performed the Pippi Salle procedure in 6 males and 6 females with severe intrinsic sphincter deficiency between March 2003 and August 2013. Median patient age was 15 years (range 6 to 45). Mean followup was 75 months (range 17 to 142). Six males and 3 females had neurogenic intrinsic sphincter deficiency (spina bifida in 8 and spinal cord injury in 1). Three females had anatomical intrinsic sphincter deficiency (idiopathic bladder hypoplasia in 2 and pseudo-ureterocele in 1). Four patients had previously undergone bladder neck surgery, 3 had been treated with endoscopic injection of collagen, 2 had undergone fascial sling and 1 had been treated with tension-free vaginal tape surgery. The Pippi Salle procedure was performed alone (2 patients), or in combination with bladder augmentation (4) or catheterizable abdominal stoma (1), or both (5)., Results: Complete dryness was achieved in 7 patients (58%). Of 9 patients with neurogenic intrinsic sphincter deficiency 7 (78%) achieved complete dryness. Eight patients experienced complications, including continued urinary incontinence (5), difficulty catheterizing per urethra (3) and urinary calculi (1). These 8 patients were successfully treated with additional endoscopic interventions, including injection of collagen in 4, injection of dextranomer-hyaluronic acid in 1, transurethral incision of urethral kink in 3 and vesicolithotripsy in 1. After these simple interventions complete dryness was achieved in all 12 patients., Conclusions: Although we experienced some minor complications in the short term, most patients were simply and successfully treated with endoscopic surgery. The long-term results of the Pippi Salle procedure are promising., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

A 66 years old man visited our hospital with a chief complaint of right flank pain and abdominal palpable mass. Abdominal enhanced computed tomography scan showed a large cystic mass with infiltrating surrounding tissue in the right kidney. We diagnosed it infected cystic renal cell carcinoma because of high grade fever and acute inflammatory response. It was surgically unresectable tumor. Therefore, percutaneous puncture and drainage was performed under ultrasound guidance. In the culture of drainage fluid, Escherichia coli (E. coli) was isolated. Then, we confirmed reduction in the size of the tumor, right radical nephrectomy was performed. Because of tumor invasion to ascending colon, we performed the excision of right kidney together with ascending colon. Histological study confirmed target-shaped Michaelis-Gutmann body, and the definitive diagnosis was malacoplakia of the kidney. We reported a case of renal malacoplakia that was difficult to distinguish from cystic renal cell carcinoma. Our case is 12th case of renal malacoplakia in the Japanese literature.

Emphysematous cystitis is a rare condition characterized by air formation in and around the bladder wall by gas-forming organisms. An 89-year-old non-diabetic man with benign prostatic hyperplasia and neurogenic bladder presented at our hospital with fever and lower abdominal pain. Urinalysis and urine culture revealed pyuria and bacteriuria with Citrobacter freundii. Abdominal computed tomography revealed intramural gas, which suggested the diagnosis of emphysematous cystitis. He recovered and the intramural gas appeared to have disappeared on the abdominal computed tomography after urinary drainage and antibiotic therapy. Ninty-nine cases of emphysematous cystitis have been reported in Japan including this case.

Objective: To determine whether real-time elastography can be used to detect prostate cancer as a relatively non-invasive modality based on the tissue strain value., Patients and Methods: Seventeen patients underwent real-time elastography in conjunction with digital rectal examination (DRE), conventional gray-scale transrectal ultrasonography (TRUS), color Doppler ultrasonography (CDUS), and magnetic resonance imaging (MRI) prior to radical prostatectomy. The elastogram was compared to findings of conventional modalities and pathological findings of prostatectomy specimens. To obtain the elastogram, compression of the prostate was performed along with a visual indicator on a video screen., Results: Twenty of 27 pathologically confirmed tumors were detected with real-time elastography. The cancer detection rate with real-time elastography was superior to the rates of other modalities and nearly equal to both on the anterior side (75.0%) and the posterior side (73.7%) of the prostate. A higher tumor detection rate for real-time elastography was observed for tumors with a higher Gleason score and larger tumor volume., Conclusion: In our preliminary study, real-time elastography in conjunction with gray-scale TRUS is a non-invasive modality to detect prostate cancer.

Objectives: To determine the safety and efficacy of combination chemotherapy with docetaxel (DTX), estramustine phosphate (EMP), and carboplatin (CBDCA) in patients with hormone-refractory prostate cancer (HRPC)., Methods: This study included a total of 40 HRPC patients. We evaluated the activity of the following schedule: weekly DTX 30 mg/m(2) iv, daily EMP 10mg/kg po, and CBDCA AUC=6 iv on day 1 of a every 4-wk cycle. Treatment was continued until disease progression or excessive toxicity., Results: All patients were assessable for response. A median of six consecutive cycles was administered per patient. Levels of prostate-specific antigen decreased by more than 50% in 95.0% of the patients. Consumption of medication for cancer-induced pain was reduced in 84.6%. Partial response was attained in 66.7% of measurable lesions. Of patients with bone metastasis, 8.3% demonstrated partial response. With a median follow-up of 11.4 mo, the median time to progression was 12.0 mo, and the median overall survival time was 26.6 mo. The predominant toxicities were grade-3 or -4 anemia in 32.5% of the patients, leukopenia in 20.0%, and thrombocytopenia in 17.5%. However, all toxicity was temporary and reversible with dose reduction or temporary cessation of chemotherapeutic agents. There were no therapy-related deaths., Conclusions: Combination chemotherapy with DTX/EMP/CBDCA was found to have significant clinical activity with an acceptable toxicity profile in HRPC patients. More suitable selection of patients may be beneficial in terms of improved overall survival in the future.

To investigate a developmental profile of urinary 1 beta-hydroxylated cholic acid of preterm infants, a urinary 1 beta-hydroxylated cholic acid/total bile acid ration (%) was measured in 118 preterm infants using Gas Chromatography- Mass Spectrometry (GC-MS). Following results were obtained: (1) The mean value of urinary 1 beta-hydroxylated cholic acid/total bile acid ratio (%) increased rapidly from birth to 0 weeks of corrected postnatal age (Expected date of confinement was denoted as day 0), and decreased thereafter. Thus the mean ratio (%) at week 0 was approximately 50%, and it became less than 10% at week 40. (2) The earlier the gestational weeks of preterm infants at birth were, the smaller the ratio (%) was. (3) The developmental profile of the urinary 1 beta-hydroxylated cholic acid/total bile acid ratio (%) from birth to 110 weeks of corrected postnatal age had almost the same pattern regardless of gestational weeks at birth, weight at birth and whether it was small-for-gestational-age (SGA) or appropriate-for-gestational-age (AGA) in preterm infants. (4) The developmental profile of the urinary 1 beta-hydroxylated cholic acid/total bile acid ratio (%) from birth to 110 weeks of corrected postnatal age had a similar pattern between males and females, although the mean ratios at -13, -10, -5, 0, 20, 60 and 80 weeks of corrected postnatal age of the female group tended to be consistently higher than those of the male group in preterm infants. Based on these results, a possible application of the present analysis in diagnosing hepato-biliary disorders is being investigated.