Hideo Nakai

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)u2028Level of Evidenceu20034

Insignificant impact of VUR on the progression of CKD in children with CAKUT

BackgroundVesicoureteral reflux (VUR) is associated with an increased risk of kidney disorders. It is unclear whether VUR is associated with progression from chronic kidney disease (CKD) to end-stage kidney disease (ESKD) in children with congenital anomalies of the kidney and urinary tract (CAKUT).MethodsWe conducted a 3-year follow-up survey of a cohort of 447 children with CKD (stage 3–5). Rates of and risk factors for progression to ESKD were determined using the Kaplan–Meier method and Cox regression respectively.ResultsCongenital anomaly of the kidney and urinary tract was the primary etiology in 278 out of 447 children; 118 (42.4xa0%) had a history of VUR at the start of the cohort study. There were significantly more boys than girls with VUR, whereas the proportions were similar in children without VUR. The types of urinary anomalies/complications of the two groups were significantly different. Three-year renal survival rates of the groups were not significantly different, irrespective of CKD stage. Age u2009<u20092xa0years and age after puberty, stage 4 or 5 CKD, and heavy proteinuria, but not history of VUR, were significantly associated with progression to ESKD.ConclusionsHistory of VUR at the start of follow-up was not associated with the progression of stage 3–5 CKD in children with CAKUT.

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

Long-Term Outcome of the Pippi Salle Procedure for Intractable Urinary Incontinence in Patients with Severe Intrinsic Urethral Sphincter Deficiency

PURPOSEnWe evaluated the long-term outcome of the Pippi Salle procedure in patients with severe intrinsic urethral sphincter deficiency.nnnMATERIALS AND METHODSnWe 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, 2xa0had 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).nnnRESULTSnComplete 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 8xa0patients were successfully treated with additional endoscopic interventions, including injection of collagen in 4, injection of dextranomer-hyaluronic acid in 1,xa0transurethral incision of urethral kink in 3 and vesicolithotripsy in 1. After these simple interventions complete dryness was achieved in all 12 patients.nnnCONCLUSIONSnAlthough 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.

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 10u2003years 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°, pu2009<u20090.001), the flexion rate decreased (before vs. after TUI, respectively: 11.8 vs. 4.1%, pu2009<u20090.001).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.

Evaluation of the Effectiveness of a Short-term Treatment and Repeat Treatment of Nocturnal Enuresis Using an Enuresis Alarm

OBJECTIVEnTo 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.nnnMATERIALS AND METHODSnClinical 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 Childrens 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.nnnRESULTSnAmong 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.nnnCONCLUSIONnEA 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.

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

Purposeu2003This 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 Methodsu2003A 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]). Resultsu2003All patients had PUV type 1 and/or 3 (i.e., nu2009=u200934 type 1, 7 type 3, and 13 types 1 and 3). There were severe (nu2009=u20091), moderate (nu2009=u200921), and mild (nu2009=u200925) 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. Conclusionsu2003PUV 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.