Shigeru Nakamura

Transurethral incision of congenital obstructive lesions in the posterior urethra in boys and its effect on urinary incontinence and urodynamic study.

Study Type – Therapy (case series)
Level of Evidence 4

A multi-center study of pediatric uroflowmetry data using patterning software

OBJECTIVE We created software for patterning uroflowmetry (UFM) curves, and validated its utility. PATIENTS AND METHODS The software patterns a given UFM curve upon four parameters: sex, voided volume, maximal flow rate, and amplitude of fluctuation. Using the software, 6 urologists from 4 institutes assessed 30 test curves. Further, 329 UFM curves obtained from children presenting to 3 institutes for daytime and/or nighttime wetting were assessed. Clinical presentation was divided into 3 groups: group A, daytime incontinence; group B, non-monosymptomatic nocturnal enuresis without daytime wetting; and group C, monosymptomatic nocturnal enuresis. RESULTS Using the software, inter-rater agreement ranged from 0.85 to 1.00 (mean, 0.93 ± 0.04). It could pattern 310 out of 329 clinical curves. In each institute, the tower pattern was prevalent according to severity of daytime symptoms, although not significantly. The merged data showed that the percent tower pattern significantly correlated with presence of daytime symptoms (groups A, B, and C, 29.7%, 27.0%, and 16.3%, respectively; p < 0.05). No correlation with daytime symptoms was noted for fluctuated (staccato and interrupted) and plateau patterns. CONCLUSION The software creates a common platform for evaluating pediatric UFM, enabling extraction of common and biased features of different cohorts, and their integration into one single cohort.

Urinary ascites in a fetus with posterior urethral valve: antenatal diagnosis.

Posterior urethral valves are reportedly associated with urine collection in the retroperitoneal or abdominal cavity in 1.0– 8.5% of cases, with the latter, urinary ascites, being less frequent. Although the mechanism of urinary ascites is unclear, bladder rupture is one culprit. We read the article by Gürgöze et al., “A rare case of ascites in a newborn: posterior urethral valve”, in which posterior urethral valve caused kidney rupture, not bladder rupture, leading to urinary ascites in a 17-day-old boy. The authors emphasized that in this condition, urinary ascites can be caused by not only bladder rupture, but also urine extravasation from the upper urinary tract, also previously reported to be a culprit of neonatal urinary ascites. The report by Gürgöze et al. ended with, “antenatal ultrasonography should be performed in all pregnant women”, which was not performed in this case. We agree with this comment. We experienced a similar case of urinary ascites due to urine extravasation from the upper urinary tract associated with posterior urethral valve, but in a fetus, not a neonate. Antenatal ultrasound worked. Ultrasound in the 26th week revealed giant bladder (megacystis) and bilateral hydronephrosis in a male fetus (Fig. 1a). In the 28th week, ascites appeared, and the mother was referred. Megacystis and bilateral hydronephrosis, which had been observed 2 weeks previously, were absent. Massive ascites (Fig. 1b) pushed the diaphragm cephalad, compressing the thoracic cavity. Retroperitoneal fluid collection around the left kidney was observed (Fig. 1c). The most probable antenatal diagnosis was as follows: distal urinary tract obstruction, such as posterior urethral valve, caused megacystis and hydronephrosis. Urine was extravasated from the left upper urinary tract, finally leading to urinary ascites. The next day (28 weeks of gestation), Doppler flowmetry revealed mitral/tricuspid regurgitation, a heart failure sign, possibly caused by thoracic compression by ascites, requiring emergency cesarean section. The male infant weighed 1470 g with 1/5-minApgar scores of 3/7. Ultrasound revealed massive ascites and fluid retention around the left kidney. Cystoscopy revealed no bladder rupture. Posterior

Next‐generation sequencing for patients with non‐obstructive azoospermia: implications for significant roles of monogenic/oligogenic mutations

Azoospermia affects up to 1% of adult men. Non‐obstructive azoospermia is a multifactorial disorder whose molecular basis remains largely unknown. To date, mutations in several genes and multiple submicroscopic copy‐number variations (CNVs) have been identified in patients with non‐obstructive azoospermia. The aim of this study was to clarify the contribution of nucleotide substitutions in known causative genes and submicroscopic CNVs in the genome to the development of non‐obstructive azoospermia. To this end, we conducted sequence analysis of 25 known disease‐associated genes using next‐generation sequencing and genome‐wide copy‐number analysis using array‐based comparative genomic hybridization. We studied 40 Japanese patients with idiopathic non‐obstructive azoospermia. Functional significance of molecular alterations was assessed by in silico analyses. As a result, we identified four putative pathogenic mutations, four rare polymorphisms possibly associated with disease risk, and four probable neutral variants in 10 patients. These sequence alterations included a heterozygous splice site mutation in SOHLH1 and a hemizygous missense substitution in TEX11, which have been reported as causes of non‐obstructive azoospermia. Copy‐number analysis detected five X chromosomal or autosomal CNVs of unknown clinical significance, in addition to one known pathogenic Y chromosomal microduplication. Five patients carried multiple molecular alterations. The results indicate that monogenic and oligogenic mutations, including those in SOHLH1 and TEX11, account for more than 10% of cases of idiopathic non‐obstructive azoospermia. Furthermore, this study suggests possible contributions of substitutions in various genes as well as submicroscopic CNVs on the X chromosome and autosomes to non‐obstructive azoospermia, which require further validation.

Labial adhesion causing voiding but not sexual problems in a married woman

A married woman of reproductive age had labial adhesion with voiding difficulty. She and her husband had not been bothered by their inability to engage in sexual intercourse for the 10 years of their marriage. Surgical incision and reconstruction disclosed the normal vaginal vestibule and urethral meatus. Six months after surgery, her labium was fully open without recurrence. We must be aware that labial adhesion may occur and be hidden in a woman of reproductive age, even when the patient does not notice any ‘abnormality’ in her genitalia.

The changes of urethral morphology recognized in voiding cystourethrography after endoscopic transurethral incision for posterior urethral valve in boys with intractable daytime urinary incontinence and nocturnal enuresis

PurposeEndoscopic 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.MethodsBetween 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.ResultsAfter 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).ConclusionsThis 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.

Aggressive diagnosis and treatment for posterior urethral valve as an etiology for vesicoureteral reflux or urge incontinence in children

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.

The Endoscopic Morphological Features of Congenital Posterior Urethral Obstructions in Boys with Refractory Daytime Urinary Incontinence and Nocturnal Enuresis

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.

STX2 is a causative gene for nonobstructive azoospermia

STX2 encodes a sulfoglycolipid transporter. Although Stx2 nullizygosity is known to cause spermatogenic failure in mice, STX2 mutations have not been identified in humans. Here, we performed STX2 mutation analysis for 131 Japanese men clinically diagnosed with nonobstructive azoospermia. As a result, we identified a homozygous frameshift mutation [c.8_12delACCGG, p.(Asp3Alafs*8)] in one patient. The mutation‐positive patient exhibited loss‐of‐heterozygosity for 58.4 Mb genomic regions involving STX2, suggesting possible parental consanguinity. The patient showed azoospermia, relatively small testes, and a mildly elevated follicle stimulating hormone level, but no additional clinical features. Testicular histology of the patient showed universal maturation arrest and multinucleated spermatocytes, which have also been observed in mice lacking Stx2. PCR‐based cDNA screening revealed wildtype STX2 expression in various tissues including the testis. Our results indicate that STX2 nullizygosity results in nonsyndromic maturation arrest with multinucleated spermatocytes, and accounts for a small fraction of cases with nonobstructive azoospermia.

Top-down approach is possible strategy for predicting breakthrough fUTIs and renal scars in infants

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.