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Prune belly syndrome (PBS) is characterized by the triad of abdominal flaccidity, a variable degree of urinary tract involvement and cryptorchidism. Most cases of PBS are sporadic and have a normal karyotype, with 95% patients being male. In the last decade, mutations in known genes that regulate embryonic genitourinary myogenesis have been identified and with increasing knowledge of these critical genes involved in bladder maldevelopment, advances can be made in genetic counseling. A multidisciplinary approach is necessary and individualization of care is recommended according to phenotypic severity. Some patients require abdominal and urinary tract reconstruction while others require as little as bilateral orchiopexies. Major treatment objectives are: preservation of renal function and upper urinary tract; polyuria management; adequate bladder emptying; improvement of corporal image and quality of life; preservation of fertility and adequate sexual function. Long-term surveillance of the urinary tract is essential up to adulthood, because functional dynamics can change over time.

Background Castration-insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has failed to provide a consensus on the anatomical and transcriptional identity of proximal prostate progenitors. Methods Here, we use single-cell RNA sequencing to obtain a complete transcriptomic profile of all epithelial cells in the mouse prostate and urethra to objectively identify cellular subtypes. Pan-transcriptomic comparison to human prostate cell types identified a mouse equivalent of human urethral luminal cells, which highly expressed putative prostate progenitor markers. Validation of the urethral luminal cell cluster was performed using immunostaining and flow cytometry. Results Our data reveal that previously identified facultative progenitors marked by Trop2, Sca-1, KRT4, and PSCA are actually luminal epithelial cells of the urethra that extend into the proximal region of the prostate, and are resistant to castration-induced androgen deprivation. Mouse urethral luminal cells were identified to be the equivalent of previously identified human club and hillock cells that similarly extend into proximal prostate ducts. Benign prostatic hyperplasia (BPH) has long been considered an "embryonic reawakening," but the cellular origin of the hyperplastic growth concentrated in the periurethral region is unclear. We demonstrate an increase in urethral luminal cells within glandular nodules from BPH patients. Urethral luminal cells are further increased in patients treated with a 5-α reductase inhibitor. Conclusions Our data demonstrate that cells of the proximal prostate that express putative progenitor markers, and are enriched by castration in the proximal prostate, are urethral luminal cells and that these cells may play an important role in the etiology of human BPH.

Congenital anomalies of the external genitalia (CAEG) are a prevalent and serious public health concern with lifelong impacts on the urinary function, sexual health, fertility, tumor development, and psychosocial wellbeing of affected individuals. Complications of treatment are frequent, and data reflecting long-term outcomes in adulthood are limited. To identify a path forward to improve treatments and realize the possibility of preventing CAEG, the National Institute of Diabetes and Digestive and Kidney Diseases and the American Urological Association convened researchers from a range of disciplines to coordinate research efforts to fully understand the different etiologies of these common conditions, subsequent variation in clinical phenotypes, and best practices for long term surgical success. Meeting participants concluded that a central data hub for clinical evaluations, including collection of DNA samples from patients and their parents, and short interviews to determine familial penetrance (small pedigrees), would accelerate research in this field. Such a centralized datahub will advance efforts to develop detailed multi-dimensional phenotyping and will enable access to genome sequence analyses and associated metadata to define the genetic bases for these conditions. Inclusion of tissue samples and integration of clinical studies with basic research using human cells and animal models will advance efforts to identify the developmental mechanisms that are disrupted during development and will add cellular and molecular granularity to phenotyping CAEG. While the discussion focuses heavily on hypospadias, this can be seen as a potential template for other conditions in the realm of CAEG, including cryptorchidism or the exstrophy-epispadias complex. Taken together with long-term clinical follow-up, these data could inform surgical choices and improve likelihood for long-term success.

Prune Belly Syndrome (PBS) is a congenital multisystem myopathy with mild to lethal severity. While of uncertain etiology, 95% male predominance and familial occurrence suggest a genetic basis. As copy number variations (CNVs) can cause unexplained genetic disorders, we tested for novel CNVs in a large PBS population. We genotyped 21 unrelated PBS patients by high-resolution array comparative genomic hybridization (aCGH) and phenotyped using a novel PBS severity scoring system. Available parents were screened for detected CNV via quantitative PCR (qPCR). We additionally screened for recurrence of identified novel candidate CNVs on 106 PBS probands by qPCR. We identified 10 CNVs in 8 of 21 PBS patients tested (38%). Testing confirmed inheritance from an unaffected biological parent in six patients; parental samples were unavailable in two probands. One candidate CNV includes duplication of the X-chromosome AGTR2 gene, known to function in urinary tract development. Subsequent screening of the larger PBS cohort did not identify any recurrent CNVs. Presence of CNV did not correlate with PBS severity scoring. CNVs were uncommon in this large PBS population, but analysis of identified variants may inform disease pathogenesis and reveal targets for therapeutic intervention for this rare, severe disorder.

To assess the effect of implementing an emergency surgery track for testicular torsion transfers. We hypothesized that transferring children from other facilities diagnosed with torsion straight to the operating room (STOR) would decrease ischemia time, lower costs, and reduce testicular loss.Demographics, arrival to incision time, hospital cost in dollars, and testicular outcome (determined by testicular ultrasound) at follow-up were retrospectively compared in all patients transferred to our tertiary care children's hospital with a diagnosis of testicular torsion from 2012 to 2016. Clinical data for STOR and non-STOR patients were compared by Wilcoxon rank-sum, 2-tailed t test, or Fisher exact test as appropriate.Sixty-eight patients met inclusion criteria: 35 STOR and 33 non-STOR. Children taken STOR had a shorter median arrival to incision time (STOR: 54 minutes vs non-STOR: 94 minutes, P .0001) and lower median total hospital costs (STOR: $3882 vs non-STOR: $4419, P .0001). However, only 46.8% of STOR patients and 48.4% of non-STOR patients achieved surgery within 6 hours of symptom onset. Testicular salvage rates in STOR and non-STOR patients were not significantly different (STOR: 68.4% vs non-STOR: 36.8%, P = .1), but follow-up was poor.STOR decreased arrival to incision time and hospital cost but did not affect testicular loss. The bulk of ischemia time in torsion transfers occurred before arrival at our tertiary care center. Further interventions addressing delays in diagnosis and transfer are needed to truly improve testicular salvage rates in these patients.

Background Prune belly syndrome (PBS) is a rare, multi-system congenital myopathy primarily affecting males that is poorly described genetically. Phenotypically, its morbidity spans from mild to lethal, however, all isolated PBS cases manifest three cardinal pathological features: 1) wrinkled flaccid ventral abdominal wall with skeletal muscle deficiency, 2) urinary tract dilation with poorly contractile smooth muscle, and 3) intra-abdominal undescended testes. Despite evidence for a genetic basis, previously reported PBS autosomal candidate genes only account for one consanguineous family and single cases. Methods We performed whole exome sequencing (WES) of two maternal adult half-brothers with syndromic PBS (PBS + Otopalatodigital spectrum disorder [OPDSD]) and two unrelated sporadic individuals with isolated PBS and further functionally validated the identified mutations. Results We identified three unreported hemizygous missense point mutations in the X-chromosome gene Filamin A (FLNA) (c.4952 C > T (p.A1448V), c.6727C > T (p.C2160R), c.5966 G > A (p.G2236E)) in two related cases and two unrelated sporadic individuals. Two of the three PBS mutations map to the highly regulatory, stretch-sensing Ig19–21 region of FLNA and enhance binding to intracellular tails of the transmembrane receptor β-integrin 1 (ITGβ1). Conclusions FLNA is a regulatory actin-crosslinking protein that functions in smooth muscle cells as a mechanosensing molecular scaffold, transmitting force signals from the actin-myosin motor units and cytoskeleton via binding partners to the extracellular matrix. This is the first evidence for an X-linked cause of PBS in multiple unrelated individuals and expands the phenotypic spectrum associated with FLNA in males surviving even into adulthood.

Clostridioides difficile causes severe colitis in people and is a significant enteric pathogen in many species of animals, including swine, horses, and potentially cattle. C. difficile is shed in feces, and transmission occurs horizontally via the fecal-oral route. Livestock has been suggested as a potential reservoir for C. difficile, and while studies have shown that swine and farm workers can be colonized with identical clones of C. difficile, the zoonotic transmission of C. difficile from livestock to people has not been definitively demonstrated. The goal of this study was to determine whether dairy calves and dairy farm workers harbored genetically similar isolates of C. difficile. First, we validated a glove juice protocol for detecting C. difficile on farm workers’ hands. We then visited 23 farms and collected 1) fecal samples from 92 dairy calves, 2) hand rinsates from 38 dairy farm workers, and 3) fecal samples from five of the dairy farm workers who were willing to submit them. All samples underwent anaerobic culture and qPCR to detect C. difficile. C. difficile was detected on 15 of the farms (65.2%, 95% confidence interval (CI) 42.7%–83.6%) and in 28 calves (30.4%, 95% CI 21.2–40.9%) but in none of the hand rinsates or human fecal samples. Thus, the zoonotic transmission of C. difficile on dairy farms could not be demonstrated, and dairy farmers did not appear to be at increased risk of acquiring C. difficile via the fecal-oral route.

The TWIST (Testicular Workup for Ischemia and Suspected Torsion) score uses urological history and physical examination to assess risk of testis torsion. Parameters include testis swelling (2 points), hard testis (2), absent cremasteric reflex (1), nausea/vomiting (1) and high riding testis (1). While TWIST has been validated when scored by urologists, its diagnostic accuracy among nonurological providers is unknown. We assessed the usefulness of the TWIST score when determined by nonurological nonphysician providers, mirroring emergency room evaluation of acute scrotal pain.Children with unilateral acute scrotum were prospectively enrolled in a National Institutes of Health clinical trial. After undergoing basic history and physical examination training, emergency medical technicians calculated TWIST score and determined Tanner stage per pictorial diagram. Clinical torsion was confirmed by surgical exploration. All data were captured into REDCap™ and ROC curves were used to evaluate the diagnostic usefulness of TWIST.Of 128 patients (mean age 11.3 years) 44 (13.0 years) had torsion. TWIST score cutoff values of 0 and 6 derived from ROC analysis identified 31 high, 57 intermediate and 40 low risk cases (positive predictive value 93.5%, negative predictive value 100%).TWIST score assessed by nonurologists, such as emergency medical technicians, is accurate. Low risk patients do not require ultrasound to rule out torsion. High risk patients can proceed directly to surgery, with more than 50% avoiding ultrasound. In the future emergency medical technicians and/or emergency room triage personnel may be able to calculate TWIST score to guide radiological evaluation and immediate surgical intervention at initial assessment long before urological consultation.

OBJECTIVE To design a novel system of scoring prune belly syndrome (PBS) phenotypic severity at any presenting age and apply it to a large pilot cohort. PATIENTS AND METHODS From 2000 to 2017, patients with PBS were recruited to our prospective PBS study and medical records were cross-sectionally analysed, generating individualised RUBACE scores. We designed the pragmatic RUBACE-scoring system based on six sub-scores (R: renal, U: ureter, B: bladder/outlet, A: abdominal wall, C: cryptorchidism, E: extra-genitourinary, generating the acronym RUBACE), yielding a potential summed score of 0-31. The 'E' score was used to segregate syndromic PBS and PBS-plus variants. The cohort was scored per classic Woodard criteria and RUBACE scores compared to Woodard category. RESULTS In all, 48 males and two females had a mean (range) RUBACE score of 13.8 (8-25) at a mean age of 7.3 years. Segregated by phenotypic categories, there were 39 isolated PBS (76%), six syndromic PBS (12%) and five PBS-plus (10%) cases. The mean RUBACE scores for Woodard categories 1, 2, and 3 were 20.5 (eight patients), 13.8 (25), and 10.6 (17), respectively (P

PURPOSE: A rapid test for testicular torsion in children may obviate the delay for testicular ultrasound. In this study we assessed testicular tissue percent oxygen saturation (%StO2) measured by transscrotal near infrared spectroscopy as a diagnostic test for pediatric testicular torsion. MATERIALS AND METHODS: This was a prospective comparison to a gold standard diagnostic test study that evaluated near infrared spectroscopy %StO2 readings to diagnose testicular torsion. The gold standard for torsion diagnosis was standard clinical care. From 2013 to 2015 males with acute scrotum for more than 1 month and who were less than 18 years old were recruited. Near infrared spectroscopy %StO2 readings were obtained for affected and unaffected testes. Near infrared spectroscopy Δ%StO2 was calculated as unaffected minus affected reading. The utility of near infrared spectroscopy Δ%StO2 to diagnose testis torsion was described with ROC curves. RESULTS: Of 154 eligible patients 121 had near infrared spectroscopy readings. Median near infrared spectroscopy Δ%StO2 in the 36 patients with torsion was 2.0 (IQR −4.2 to 9.8) vs −1.7 (IQR −8.7 to 2.0) in the 85 without torsion (p=0.004). AUC for near infrared spectroscopy as a diagnostic test was 0.66 (95% CI 0.55–0.78). Near infrared spectroscopy Δ%StO2 of 20 or greater had a positive predictive value of 100% and a sensitivity of 22.2%. Tanner stage 3-5 cases without scrotal edema or with pain for 12 hours or less had an AUC of 0.91 (95% CI 0.86–1.0) and 0.80 (95% CI 0.62–0.99), respectively. CONCLUSIONS: In all children near infrared spectroscopy readings had limited utility in diagnosing torsion. However, in Tanner 3-5 cases without scrotal edema or with pain 12 hours or less, near infrared spectroscopy discriminated well between torsion and nontorsion.

Less than 50% of cases of 46,XY disorders of sex development are genetically defined after karyotyping and/or sequencing of known causal genes. Since copy number variations are often missed by karyotyping and sequencing, we assessed patients with unexplained 46,XY disorders of sex development using array comparative genomic hybridization for possible disease causing genomic variants.DNA from unexplained cases of 46,XY disorders of sex development were tested by whole genome array comparative genomic hybridization. In cases where novel copy number variations were detected parental testing was performed to identify whether copy number variations were de novo or inherited.Of the 12 patients who underwent array comparative genomic hybridization testing 2 had possible copy number variations causing disorders of sex development, both maternally inherited microdeletions. One case, with a maternal history of premature ovarian failure, had a cosegregating microdeletion on 9q33.3 involving NR5A1. The other case, with a maternal family history of congenital heart disease, had a cosegregating microdeletion on 8p23.1 upstream of GATA4.In this cohort copy number variations involving or adjacent to known causal genes led to 46,XY disorders of sex development in 2 of 12 previously unexplained cases (17%). Copy number variation testing is clinically indicated for unexplained cases of 46,XY disorders of sex development to aid in genetic counseling for family planning.

Cryptorchidism is one of the most common pediatric disorders of the male endocrine glands and the most common genital disorder identified at birth. This guideline is intended to provide physicians and non-physician providers (primary care and specialists) with a consensus of principles and treatment plans for the management of cryptorchidism (typically isolated non-syndromic).A systematic review and meta-analysis of the published literature was conducted using controlled vocabulary supplemented with key words relating to the relevant concepts of cryptorchidism. The search strategy was developed and executed by reference librarians and methodologists to create an evidence report limited to English-language, published peer-reviewed literature. This review yielded 704 articles published from 1980 through 2013 that were used to form a majority of the guideline statements. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence-based data.Guideline statements were created to inform clinicians on the proper methods of history-taking, physical exam, and evaluation of the boy with cryptorchidism, as well as the various hormonal and surgical treatment options.Imaging for cryptorchidism is not recommended prior to referral, which should occur by 6 months of age. Orchidopexy (orchiopexy is the preferred term) is the most successful therapy to relocate the testis into the scrotum, while hormonal therapy is not recommended. Successful scrotal repositioning of the testis may reduce but does not prevent the potential long-term issues of infertility and testis cancer. Appropriate counseling and follow-up of the patient is essential.

We investigated the usefulness of transscrotal near infrared spectroscopy that measures testicular oxygen saturation (StO2%) in the diagnosis of testicular torsion vs other causes of the acute scrotum in adults.Between January and May 2009, 16 adult males presenting with acute scrotum underwent StO2% measurement of the affected and unaffected testis using near infrared spectroscopy followed by color Doppler ultrasound. If surgically explored, near infrared spectroscopy was performed at surgery and on postoperative day 1. Data were presented as means ± SD and/or normalized to the internal control. Cutoff value was generated for the StO2% difference between the affected testis and control side.Sixteen males with acute scrotum of mean duration 12 hours were enrolled. Of 11 patients with abnormal Doppler undergoing surgical exploration, mean StO2% of the affected testis at presentation and at surgery decreased from 40.09 ± 2.66 (range 36 to 44) to 37.18 ± 3.31 (range 32 to 42), respectively, while StO2% of the unaffected testis remained 63.09 (range 55 to 69) both at presentation (SD 4.72) and at surgery (SD 4.98). Of the 11 surgically explored, 4 had orchiectomy and 7 patients underwent surgical detorsion. At presentation and at surgical exploration of the detorsed group, the mean normalized difference between the StO2% values of the affected and unaffected sides was -16.12 and -25.9, respectively. A cutoff value of -11.5 was measured for the StO2% difference between the affected testis and control side at presentation in patients who underwent surgery.Near infrared spectroscopy identified all surgically confirmed cases of testicular torsion when affected testis StO2% was more than 11.5 units lower than the contralateral testis. In pilot testing, near infrared spectroscopy is a rapid, noninvasive, easy and safe method for the differential diagnosis of adult human testicular torsion.

Summary Introduction Symptomatic pediatric ureterocele has diverse manifestations, making evidence-based management impractical. Thus, detailed visualization of ureterocele anatomy prior to first surgical incision is invaluable. Retrograde ureterocelogram (RUC) is a simple, underutilized radiologic technique that can be performed during cystoscopy. This study sought to determine whether RUC changes surgical management by more accurately depicting the complex ureteral and ureterocele anatomy, compared with renal ultrasound (US) and voiding cystourethrography (VCUG). Methods Patients who underwent surgical management of ureterocele from 2003 to 2015 were identified; those who received concomitant fluoroscopic RUC were selected for the case series. Data collected included: demographics, pre-operative evaluation, surgical interventions, and outcomes. The RUC images were individually examined, and the anatomic impression compared with previous renal US and VCUG. Novel RUC findings not previously appreciated by the pre-operative evaluation were noted. The RUC was performed by cystoscopically inserting a needle into the ureterocele and injecting contrast retrograde. If indicated, simultaneous PIC (Positioning the Instillation of Contrast) cystography was performed. Results Of the 43 patients that underwent surgery for suspected ureterocele, 28 underwent cystoscopy + RUC (10 M: 18 F) at a median age of 4.6 months and median follow-up of 37.0 months. All patients had prior US, 25 had prior VCUG, and 20 had prior radionuclide studies. Ureteroceles were either duplex system (n = 21) or single system (n = 7); 17 were ectopic into the bladder neck or urethra; seven were intravesical; and four were pseudoureteroceles. Fourteen patients underwent concomitant transurethral incision of the ureterocele (TUIU); two were deferred for surgery; and 11 received concomitant definitive surgery (e.g., nephrectomy). The RUC illuminated novel aspects of the anatomy in 20 of the 28 patients. No adverse events occurred. Notably, in nine of the 28 children, significant observations from RUC prompted change to the pre-operative surgical plan. Discussion Retrograde ureterocelogram clearly revealed ureterocele ectopy, pseudoureterocele, ureterocele disproportion, and unsuspected duplex systems, making it a useful adjunct to standard US and VCUG studies. Retrograde ureterocelogram can also be used to fluoroscopically verify decompression of the ureterocele post incision, document severity of ureteral dilation, and teach residents about the great damage generated by ureterocele variations. Limitations of RUC included increasing radiation dose and overall cost. The study design was limited by its small size, retrospective approach, selection bias, and availability of RUC images. Conclusions While not indicated in routine ureterocele management, intraoperative RUC further defined ureterocele anatomy in nearly all cases and yielded changes to the original surgical plan frequently enough to merit greater use in complex patients. Download : Download high-res image (79KB) Download : Download full-size image Figure . Example of RUC to illustrate complex ureterocele anatomy. In a 6-week-old febrile male with a right renal mass and grade IV VUR, RUC was performed to clarify the anatomy concomitant with a planned right nephrectomy. RUC revealed an ectopic right ureter and ureterocele, which appeared to have ruptured and opened into the posterior wall of the prostatic urethra. This did not change the nephrectomy but provided valuable reference for subsequent lower tract interventions.

Empirical studies on the impact of intimate partner violence (IPV) on children have burgeoned over the last three decades. Notably absent from existing approaches to studying children exposed to IPV, however, is attention to how various positionalities intersect to impact the experiences of children and their families. In fact, while the importance of an intersectional framework for understanding IPV has been discussed for over two decades, little or no attention has been given to issues of children’s exposure to IPV. In this article, we examine the current state of the literature on children exposed to IPV through an exploratory meta-analysis, finding limited application of intersectionality and a focus on discrete categories of difference. We then demonstrate why and how an intersectional framework should be applied to children exposed to IPV, with specific strategies for research and policy. We suggest a child-centered approach that recognizes diversity among children exposed to IPV, extending the challenge to traditional “one-size-fits-all” models to include an intersectionality-informed stance.

Fragile X syndrome, the most common form of X-linked intellectual disability, results from transcriptional silencing of the FMR1 gene. As of yet, the phenotypic consequences of the duplication of FMR1 have not been well characterized. In this report, we characterize the clinical features in two females with duplications involving only the FMR1 gene. In addition, we describe the phenotypes of two subjects with deletion of FMR1 and show that both loss and gain of FMR1 copy number can lead to overlapping neurodevelopmental phenotypes. Our report supports the notion that FMR1 gene dosage is important for normal neurocognitive function.

While the timely diagnosis and management of pediatric torsion can lead to testicular salvage, limited data exist on rates of orchiopexy vs orchiectomy and associated factors. Thus, we examined the Pediatric Health Information System database for torsion outcomes and demographics at American pediatric hospitals.Using the Pediatric Health Information System database we performed a 7-year retrospective cohort study in children 1 to 17 years old with a primary ICD-9 diagnosis of torsion, assessing CPT codes for orchiopexy and orchiectomy. Data were analyzed with SPSS®, version 17.0.Of 2,876 patients who underwent surgery for an ICD-9 diagnosis code of testicular torsion 918 (31.9%) underwent orchiectomy at a mean age of 10.7 years and 1,958 (68.1%) underwent orchiopexy at a mean age of 12.6 years (p0.0001). In the age groups 1 to 9, 10 to 13 and 14 years or greater 274 (49.9%), 311 (29.4%) and 333 patients (26.2%), respectively, underwent orchiectomy. A higher orchiectomy rate was seen at age 1 to 9 vs 10 years or greater. Torsion and orchiectomy rates did not vary by season or geographic region. A higher orchiectomy rate was seen in black vs white children (37.6% vs 28.1%) and in patients without vs with private insurance (36.7% vs 27.0%). Multivariate analysis revealed an association of age (p0.0001), race (p0.0001) and insurance status (p0.001) with orchiectomy.Nationally an average of 32% of the 411 pediatric torsion cases explored annually result in orchiectomy. Identified factors increasing the orchiectomy risk included age 1 to 9 years, black race and lack of private insurance. Efforts should continue to identify modifiable variables that can increase testicular salvage in patients with testicular torsion.

Lower urinary tract foreign bodies have been reported in both children and adults. It is helpful for urologists to review foreign body case reports to become familiar with alternative approaches for removal that may prove helpful during challenging cases. To our knowledge, we describe for the first time a degraded rare-earth magnet within the body and use of Hartmann ear forceps to remove a foreign body from the urethra under cystoscopic guidance through a limited urethrotomy.

We determined whether stone attenuation can predict stone fragmentation after shock wave lithotripsy in the pediatric population. Previous studies show that preoperative attenuation in HU on noncontrast computerized tomography predicts shock wave lithotripsy success. To our knowledge study of this parameter in the pediatric population has been lacking to date.We performed a multi-institutional review of the records of 53 pediatric patients 1 to 18 years old who underwent shock wave lithotripsy for 3.8 to 36.0 mm renal calculi. Stone size, average skin-to-stone distance and attenuation value were determined by bone windows on preoperative noncontrast computerized tomography. Success was defined as radiographically stone-free status at 2 to 12-week followup after a single lithotripsy session without the need for further sessions or ancillary procedures.After lithotripsy 33 patients (62%) were stone-free and 20 had incomplete fragmentation or required additional procedures. Mean ± SD stone attenuation in successfully treated patients vs those with incomplete fragmentation was 710 ± 294 vs 994 ± 379 HU (p = 0.007). Logistical regression analysis revealed that only attenuation in HU was a significant predictor of success. When patients were stratified into 2 groups (less than 1,000 and 1,000 HU or greater), the shock wave lithotripsy success rate was 77% and 33%, respectively (p0.003).Stone attenuation less than 1,000 HU is a significant predictor of shock wave lithotripsy success in the pediatric population. This finding suggests that attenuation values have a similar predictive value in the pediatric population as that previously reported in the adult population.

OBJECTIVE Ureteropelvic junction obstruction (UPJ) can be caused by intrinsic disorganization or extrinsic compression from crossing vessels (CV). What is not clear is whether there is also intrinsic UPJ pathology in patients with CV. Recent surgeries, such as the Hellstrom vascular hitch procedure, move the CV cephalad without resecting the UPJ, which presumes no intrinsic narrowing. Our aim was to determine whether the histologic features of the 2 types of UPJ obstruction are distinct enough to enable a blinded pathologist to histologically identify the cause of obstruction. METHODS We reviewed all patients undergoing pyeloplasties from 2000 to 2006. All CV cases with available pathology were selected. A random selection of intrinsic cases was used as controls. One blinded pathologist reviewed the histology, specifically scoring muscle and collagen density. RESULTS Sixteen patients were reviewed. Seven had CV and 9 had intrinsic obstruction. Muscle density was different between the 2 groups with CV denser compared with intrinsic (P = .005). The pathologist correctly assigned the cause of obstruction in 5/7 (71%) of CV and 7/9 (78%) of intrinsic cases (P = .039). CONCLUSIONS Identification of a significant CV intraoperatively does translate to a discernible appearance histologically.

PURPOSE: The testicular hormone Insl3 is critical for mouse gubernacular development. Knockout mice exhibit bilateral intra-abdominal cryptorchidism with absent gubernaculum. Prior studies described torsion of the vas deferens in Insl3 mutant mice. We performed a detailed anatomical analysis of the vas deferens and testis in Insl3 mutant mice to characterize associated anomalies further. MATERIALS AND METHODS: Insl3 wild-type (Insl3(+/+)), heterozygous (Insl3(+/-)) and knockout (Insl3(-/-)) male mice were examined either prepubertally (postnatal day 23) or in adulthood (postnatal day 90 or later). The macroscopic appearance, characteristics, and mobility of the testes and spermatic cord were recorded. RESULTS: We examined 56 prepubertal and 33 adult mice (175 testes, 28 [20:8] Insl3(+/+), 97 [60:37] Insl3(+/-), 50 [32:18] Insl3(-/-)). Unlike normal Insl3(+/+) testes, 94% of Insl3(-/-) testes were located intra-abdominally at all ages. Delayed descent occurred in Insl3((+/-)) testes, since 37% of postnatal day 23 and 8% of P90 or later testes were intra-abdominal. Vas elongation/convolution and spermatic cord twisting were noted in 65% of Insl3(-/-), 27% of Insl3((+/-)) and 0% of Insl3(+/+) testes. While all Insl3(+/+) testes were normal, 5% of Insl3((+/-)) and 32% of Insl3(-/-) testes showed significant testicular pathology, including torsion, atrophy and vanished testis, which statistically increased with age. CONCLUSIONS: Poorly formed gubernacula and increased testicular mobility in Insl3 mutant mice result in spermatic cord anomalies, delayed/absent testicular descent and subsequent testicular torsion in a gene dose dependent manner. Prepubertal testicular torsion in the mutant mice predisposes to testicular atrophy and vanishing testes in adulthood. Thus, Insl3 is a candidate signaling molecule in human delayed testicular descent and torsion.

To examine differences in breastfeeding frequency, voids, and stools in infants with weight lossesoror =7% during the postpartum hospitalization.Secondary analysis of data from a primary psychometric study examining the Mother Infant Breastfeeding Progress Tool (MIBPT).A midwestern community hospital in a multicultural racially diverse community.Convenience sample of 53 breastfeeding women and infants hospitalized after birth.Data were collected during a chart review; infants were divided intooror =7% weight loss groups at 2 days postpartum, and breastfeeding frequency, voiding, and stooling were examined between groups and used to predict aor =7% weight loss at 2 days postpartum.Of the 53 infants, 20.8% lostor =7% of their birth weight. Infants who lostor =7% of their birth weight had significantly more total voids and a higher breastfeeding frequency on the day of birth than infants who lost7% of their birth weight. A logistic regression analysis resulted in total voids being the only significant predictor of aor =7% weight loss, with an odds ratio of 1.74 (95% CI=1.09, 2.75, p; .05).In the absence of other indicators of ineffective breastfeeding, breastfeeding infants who loseor =7% of their birth weight during the first 2 days postpartum might be experiencing a physiologic diuresis after birth, unrelated to their breastfeeding behaviors. More research is necessary to determine the cause of aor =7% weight loss in newborns during the first 48 hours after birth.

We report outcomes from ureteroureterostomy performed through an inguinal herniorrhaphy type incision for definitive management of ectopic ureters or ureteroceles in the absence of ipsilateral lower pole reflux.Records were reviewed for 23 consecutive patients who underwent lower ureteroureterostomy for 26 duplicated systems with ectopic ureter or ureterocele and no ipsilateral lower pole reflux. In 21 patients surgery was performed through an inguinal incision similar to that for herniorrhaphy, while a Pfannenstiel incision was used initially in the series in 2 others with bilateral duplex systems. Median patient age at operation was 10 months (range 2 to 56).At a mean followup of 26 months preoperative upper pole hydronephrosis and distal upper ureteral dilatation had resolved or improved in all cases. Preliminary cutaneous ureterostomy was performed on 4 ureters (3 patients), 2 because the recipient lower pole ureter was thought to be too small for incision and anastomosis, 1 because of purulent drainage and 1 following inadvertent transection of the lower pole ureter. Mean surgical time for inguinal ureteroureterostomy was 101 minutes and mean postoperative hospitalization was 0.6 days. Except for dextranomer/hyaluronic acid injection in 1 patient with symptomatic grade I ipsilateral lower pole reflux, no additional surgical procedures were performed after ureteroureterostomy.Lower ureteroureterostomy offers potentially definitive treatment for ectopic ureter or ureterocele without ipsilateral lower pole reflux, and can be performed through an inguinal herniorrhaphy type incision.

Childhood spontaneous bladder rupture is an uncommon event, usually associated with bladder augmentation. Occasionally it occurs in normal bladders or non-augmented bladders with a predisposing factor. We present a unique case of misdiagnosed spontaneous bladder rupture in a non-augmented bladder exstrophy patient without evidence of lower urinary outlet obstruction. His acute abdomen mimicked appendicitis and was managed with laparoscopic exploration, intraperitoneal fluid drainage, appendectomy and bladder drainage. This case highlights the need for pediatric urological consultation by surgeons in the case of an acute abdomen with free fluid in a patient with an abnormal bladder.

Laparoscopic renal surgery in pediatric urology is moving forward at a slower pace than desired. To guide beginning surgeons in what to expect in their first years of surgical experience, we present our first 6 years of pediatric laparoscopic ablative renal surgery experience to highlight the changing laparoscopic surgical parameters during this interval.We retrospectively analyzed all children who underwent laparoscopic ablative renal surgery (nephrectomy and heminephroureterectomy) performed by 1 surgeon between January 2000 and December 2005. After searching the medical, operative and anesthesia records we compared patient characteristics and operative parameters such as blood loss and operative time through the years.A total of 39 children (25 girls, 14 boys) with a mean age of 6.9 years underwent laparoscopic renal surgery. Mean operative time was 204 minutes for nephrectomy (26 cases) and 291 minutes for heminephroureterectomy (14). A statistically significant decrease in operative time was noted in the fourth year for nephrectomy cases (20 cases, p = 0.003). Blood loss decrease was significant at the fourth year after 10 cases of heminephroureterectomy (p = 0.036). Thus, operative time was the only changing parameter with experience in nephrectomy, while blood loss changed in heminephroureterectomy.This report details the operative parameters changing during the first 6 years as our experience increased in an academic setting. This outcome serves as a realistic guide regarding expectations for beginning laparoscopists, and should encourage the continuation of pediatric laparoscopic renal surgery.

The current American Academy of Pediatrics recommendation is to perform hypospadias repair at age 6 to 12 months. Primary hypospadias repair at adolescence or beyond is uncommon, and there is little reported about the postoperative course of such patients. We report the outcomes for a series of patients who underwent primary hypospadias repair at age 10 years or older.We identified patients seen at our institution between 1979 and 2002 who underwent primary hypospadias repair at age 10 years or older. Electronic and paper charts were abstracted for baseline demographics, degree of hypospadias, surgical technique, complications and reoperation.A total of 31 patients were identified, with a median available followup of 14 months. Median patient age at first hypospadias surgery was 13 years. The location of the urethral meatus was distal in 19 patients, mid shaft in 7, proximal in 4 and undetermined in 1. A variety of techniques were used, including meatal advancement and glanuloplasty, meatal based flaps, island onlay flaps, Snodgrass repair and staged procedures. Complications were noted in 48% of patients (15 of 31), including fistula (10), stricture (4), hematoma (2) and other complications (2).Although retrospective in nature, these data suggest that delay of primary hypospadias repair into the teen years or beyond may result in more complications than currently accepted for infant hypospadias repair.

Methods of stenting after laparoscopic pyeloplasty have included indwelling Double-J stents and percutaneous nephrostomy tubes. The disadvantages of these methods are that they necessitate a second surgery for stent removal or require an external drainage bag. To circumvent these issues, the tolerance, safety and outcomes of using a Double-J ureteral stent with a dangler, permitting early office removal, was investigated in a series of pediatric laparoscopic pyeloplasties.Medical records from a consecutive series of pediatric patients undergoing transperitoneal laparoscopic pyeloplasties were reviewed. Indications for surgery included ipsilateral flank pain with severe hydronephrosis (12 patients), recurrent pyelonephritis with severe hydronephrosis (2), and hematuria and flank pain (6). All patients were discharged home within 24 to 48 hours of the procedure with prophylactic oral antibiotics. The stent was removed by postoperative day 18 during a followup office visit. Patient tolerance of the indwelling stent, outpatient removal and success of pyeloplasty were assessed.A total of 20 patients underwent transperitoneal laparoscopic pyeloplasty by 1 surgeon (LAB) between 2001 and 2005. All patients underwent cystoscopy and retrograde Double-J ureteral stent placement before pyeloplasty under the same anesthesia. Mean patient age at operation was 11.3 years (median 11.3, range 4.6 to 17.2). Stents were left indwelling for a mean of 10.3 days (median 10, range 7 to 18). All patients tolerated the Double-J stent well, with 2 requiring anticholinergic therapy for mild urgency symptoms and 1 demonstrating urinary tract infection. All patients tolerated outpatient stent removal via the dangler at the office without discomfort. One patient was lost to followup. At a mean followup of 1.04 years (range 0.1 to 2.88) 17 of 19 patients (89%) had resolution of flank pain/urinary tract infections, with sonographic improvement in hydronephrosis with or without endoscopic intervention. Six patients (30%) had flank pain with or without continuous hydronephrosis and required re-stenting, and 3 also required balloon dilation. Of these 6 patients 2 (10%) had recurrent ureteropelvic junction obstruction and required open pyeloplasty. All patients are now clinically and radiologically unobstructed and asymptomatic.Pediatric transperitoneal laparoscopic pyeloplasty with indwelling Double-J ureteral stent with a dangler is successful and the stent is well tolerated. Whether the duration of ureteral stenting affects the surgical success will require further controlled long-term studies.

Summary Introduction Prune belly syndrome (PBS) extra-genitourinary (extra-GU) manifestations are serious comorbidities beyond the genitourinary (GU) anomalies of this disease. We hypothesized an underestimation of the reported frequency and understated impact on quality of life (QOL) of extra-GU comorbidities in PBS survivors beyond the newborn period. To assess this, the frequencies of extra-GU manifestations of PBS in a contemporary cohort of living patients were compared to compiled frequencies from published literature. Second, the impact of extra-GU PBS manifestations on patient/family QOL was assessed via a non-validated open-ended survey. Material and methods From 2010 to 2013, PBS survivors were prospectively recruited locally or at three PBS Network National Conventions. The family/subject was asked to complete a detailed PBS questionnaire, non-validated QOL survey, and provide medical records for review. Clinical data were extracted from medical records for local patients. The frequencies of extra-GU manifestations were compared between the contemporary, living cohort and a published literature cohort derived from PubMed. Results and discussion Seven of 706 published studies met criteria for frequencies tabulation of extra-GU PBS manifestations. This largest reported living PBS patient cohort (n = 65) was 99% male with mean age 10 years (1 month-45 years). The living PBS cohort had a statistically significantly higher incidence of gastrointestinal (63%), orthopedic (65%), and cardiopulmonary (49%) diagnoses compared to the compiled published cohort (n = 204). Eleven PBS males and 32 family members completed the QOL survey. Of these, 47% listed at least one non-GU problem (i.e. lung disease, skeletal problems, constipation) as negatively affecting their QOL; 42% listed at least one GU problem (i.e. self-catheterization, recurrent UTIs) as negatively affecting their QOL; 56% reported musculoskeletal surgery and 21% reported gastrointestinal surgery/medication as positively impacting their QOL. Conclusions In this large contemporary series, surviving individuals with PBS had a significantly higher incidence of orthopedic, gastrointestinal, and cardiopulmonary diagnoses than previously reported in PBS publications. From the patient/family QOL perspective, non-GU PBS manifestations negatively impact their QOL and treatment of these non-GU conditions improves their lives. As urologic surgeons for these medically complex patients, it is extremely important to be aware of and prepare for the high incidence of non-GU PBS comorbidities directly impacting the medical and surgical treatment and QOL of PBS patients and their families.

Dual-Chamber ATP for Rhythm Discrimination. Background: Inappropriate shocks remain a problem in patients with defibrillators (ICD). Objective: To evaluate a new discrimination algorithm for supraventricular (SVT) and ventricular (VT) tachycardias, based on the response to simultaneous (A+V) atrial (A) and ventricular (V) anti-tachycardia pacing (ATP). Methods: Patients undergoing electrophysiological testing or dual-chamber implantable cardioverter-defibrillator (ICD) implantation were enrolled (N = 32) and underwent A+V ATP through a Marquis ICD with investigational software. If persisting after ATP, the rhythm was classified as VT if the first electrical event was sensed on the V channel and as an SVT otherwise. Results: Arrhythmia sequences (N = 275; 53 VT; 222 SVT) were analyzed in 26 patients (age = 51 ± 17 years, 13 men, LVEF = 0.49 ± 0.14). In response to A+V ATP, 55% of SVT versus 41% of VT episodes were terminated (P = NS). Termination of VT but not of SVT was more likely with faster (50% at ATP/arrhythmia cycle length (CL) = 0.81 vs 8% at ATP/arrhythmia CL = 0.88, P = 0.02) but not with longer ATP bursts (P = NS). Of the 115 arrhythmias that persisted after A+V ATP, the algorithm correctly classified 24 of 24 VT (GEE-adjusted sensitivity = 100%) and 85 of 91 SVT (GEE-adjusted specificity = 93%). Proarrhythmia was noted after two A+V ATP, in the form of atrial fibrillation induction and VT acceleration. Conclusions: We describe a new algorithm that can discriminate between SVT and VT with a high sensitivity and specificity. This form of ATP can terminate 55% of SVT sequences. The performance of this new algorithm merits further testing in a large population of dual-chamber ICD patients.

Transgenic mice overexpressing the inflammatory cytokine TNF-α in the heart develop a progressive heart failure syndrome characterized by biventricular dilatation, decreased ejection fraction, decreased survival compared with non-transgenic littermates, and earlier pathology in males. TNF-α mice (TNF1.6) develop atrial arrhythmias on ambulatory telemetry monitoring that worsen with age and are more severe in males. We performed in vivo electrophysiological testing in transgenic and control mice, ex vivo optical mapping of voltage in the atria of isolated perfused TNF1.6 hearts, and in vitro studies on isolated atrial muscle and cells to study the mechanisms that lead to the spontaneous arrhythmias. Programmed stimulation induces atrial arrhythmias ( n = 8/32) in TNF1.6 but not in control mice ( n = 0/37), with a higher inducibility in males. In the isolated perfused hearts, programmed stimulation with single extra beats elicits reentrant atrial arrhythmias ( n = 6/6) in TNF1.6 but not control hearts due to slow heterogeneous conduction of the premature beats. Lowering extracellular Ca2+ normalizes conduction and prevents the arrhythmias. Atrial muscle and cells from TNF1.6 compared with control mice exhibit increased collagen deposition, decreased contractile function, and abnormal systolic and diastolic Ca2+ handling. Thus abnormalities in action potential propagation and Ca2+ handling contribute to the initiation of atrial arrhythmias in this mouse model of heart failure.

Purpose: Laparoscopic exploration for the nonpalpable testicle (NPT) has been criticized for increased costs compared with primary inguinal/scrotal exploration, mostly due to high equipment costs and the need for open inguinal/scrotal exploration in many cases. We assessed costs associated with diagnostic laparoscopy vs inguinal/scrotal exploration followed by selective open or laparoscopic treatment for unilateral NPT to identify the most important factors that influence cost. Materials and Methods: A comprehensive literature review determined the probabilities of intra-abdominal or inguinal nubbins, blind-ending vas/vessels and intra-abdominal or inguinal gonads in patients with unilateral NPT. The costs of anesthesia, equipment and operating room use were obtained from our institution or derived from the literature. A model was created using computer software to compare the costs of initial scrotal/inguinal approach or initial laparoscopic exploration in a theoretical population of boys with unilateral NPT. We established a set of assumptions and generated a series of 1-way sensitivity analyses to detect cost influencing parameters. Results: Based on the probabilities of intraoperative anatomical gonadal findings, use of reusable laparoscopic equipment and encompassing the ultimate surgical procedure needed initial laparoscopic evaluation was less costly than initial scrotal/inguinal exploration by $69 on a population basis. One-way sensitivity analyses showed that initial laparoscopic exploration was less costly if the operative time of laparoscopic exploration did not exceed 19 minutes and the cost of disposable laparoscopic equipment was less than $147. Conclusions: On a population basis initial laparoscopic evaluation of the clinically nonpalpable testicle has a cost saving advantage ($69) over initial inguinal-scrotal exploration when reusable laparoscopic equipment is primarily used, disposable equipment costs are kept low ($147 or less) and operating room time for diagnostic laparoscopy are at national standards (19 minutes or less). These findings hold true for a wide range of probabilities and duration of inguinal exploration time. Given that all of these caveats are easily achievable, cost should not be used as a factor to bias against initial laparoscopic exploration.

The Eph family constitutes the largest class of membrane bound tyrosine kinase receptors in higher vertebrates, being involved in complex cell-to-cell recognition events via their membrane anchored ligands, the ephrins. To uncover evidence for possible molecular involvement in genitourinary development, we evaluated the pattern of EphB2 expression in male and female genital tubercles (GTs) after culture with and without dihydrotestosterone (DHT).GTs of embryos from time pregnant CD1 mice heterozygous for the EphB2lacZ mutation were explanted at 12.5 to 14.5 days after conception. In these mutant mice the exons encoding the EphB2 tyrosine kinase and C-terminal domains were replaced with bacterial lacZ sequence encoding beta-galactosidase to demonstrate EphB2 expression. The GTs were microdissected, cultured for 24 to 48 hours with or without addition of 10 nM DHT and then stained with X-gal to visualize the beta-galactosidase reporter of EphB2 expression.LacZ staining was detected along the borders of the urethral plate (UP) in males. Females expressed EphB2 at the GT base but DHT exposure induced EphB2 expression along the UP. Under culture conditions, progressive approximation of the UP borders was noted in male fetuses and androgen exposed females. UP approximation was not seen in the nonexposed female tubercles.EphB2 expression appears to be temporally and spatially regulated in the developing mouse GT and differs between sexes. Male pattern of expression can be induced in the female GT by DHT exposure. Given DHT exposure alters EphB2 expression, EphB2 is a candidate androgen regulated gene. These findings may give insight into UP closure in normal and pathological conditions.

To report on the technique and utility of the holmium: YAG laser in performing laparoscopic partial nephrectomy (LPN).Three patients with indications for LPN (complex cyst, nonfunctioning lower pole, renal mass) underwent parenchymal-sparing procedures with the Ho:YAG laser. The kidney was identified using a transperitoneal laparoscopic technique. Gerota's fascia was opened, and the renal mass/nonfunctioning lower pole was resected using the laser. Settings of 0.2 J/pulse at 60 pulses/sec and 0.8 J/pulse at 40 pulses/sec were used.All three procedures were performed successfully with minimal blood loss and without the need for hilar occlusion. Although the laser alone was hemostatic, fibrin glue was applied in two cases and oxidized cellulose in one case to reinforce the tissue against delayed bleeding. There were no perioperative complications, and all patients left the hospital within 3 days.At high power settings, the Ho:YAG laser is an effective tool for LPN. It results in good hemostasis without the need for hilar occlusion. This technique promises to facilitate the laparoscopic management of renal tumors and nonfunctioning moieties of duplicated systems.

Megalourethra is a rare spectrum of urologic malformations of penile corporal structures frequently associated with multiple congenital anomalies, such as prune belly syndrome or vertebral, anorectal, cardiac, trachea-esophageal, renal, and limb (VACTERL association) defects. A 6-year-old boy with VACTERL association and proximal urethral atresia with distal fusiform megalourethra underwent staged reconstruction, including appendicovesicostomy, perineal urethrostomy, and first-stage urethroplasty with a dorsal inlay free graft of megalourethra tissue to the proximal urethral atretic region, followed by second-stage urethroplasty. At 2.6 years of follow-up, he was continent, voids per urethra without postvoid residual urine volume, and no longer performs clean intermittent catheterization by way of the appendicovesicostomy.

Background Nephrolithiasis, or urinary stone disease, in children causes significant morbidity, and is increasing in prevalence in the North American population. Therefore, medical and dietary interventions (MDI) for recurrent urinary stones in children are poised to gain increasing importance in the clinical armamentarium. Objectives To assess the effects of medical and dietary interventions (MDI) for the prevention of idiopathic urinary stones in children aged from one to 18 years. Search methods We searched multiple databases using search terms relevant to this review, including studies identified from the Cochrane Central Register of Controlled Trials (CENTRAL, 2017, Issue 1), MEDLINE OvidSP (1946 to 14 February 2017), Embase OvidSP (1980 to 14 February 2017), International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Additionally, we handsearched renal-related journals and the proceedings of major renal conferences, and reviewed weekly current awareness alerts for selected renal journals. The date of the last search was 14 February 2017. There were no language restrictions. Selection criteria Randomized controlled trials of at least one year of MDI versus control for prevention of recurrent idiopathic (non-syndromic) nephrolithiasis in children. Data collection and analysis We used standard methodologic procedures expected by Cochrane. Titles and abstracts were identified by search criteria and then screened for relevance, and then data extraction and risk of bias assessment were carried out. We assessed the quality of evidence using GRADE. Main results The search identified one study of 125 children (72 boys and 53 girls) with calcium-containing idiopathic nephrolithiasis and normal renal morphology following initial treatment with shockwave lithotripsy (SWL). Patients were randomized to oral potassium citrate 1 mEq/kg per day for 12 months versus no specific medication or preventive measure with results reported for a total of 96 patients (48 per group). This included children who were stone-free (n = 52) or had residual stone fragments (n = 44) following SWL. Primary outcomes: Medical therapy may lower rates of stone recurrence with a risk ratio (RR) of 0.19 (95% confidence interval (CI) 0.06 to 0.60; low quality evidence). This corresponds to 270 fewer stone recurrences per 1000 (133 fewer to 313 fewer) children. We downgraded the quality of evidence by two levels for very serious study limitations related to unclear allocation concealment (selection bias) and a high risk of performance, detection and attrition bias. While the data for adverse events were incomplete, they reported that six of 48 (12.5%) children receiving potassium citrate left the trial because of adverse effects. This corresponds to a RR of 13.0 (95% CI 0.75 to 224.53; very low quality evidence); an absolute effect size estimate could not be generated. We downgraded the quality of evidence for study limitations and imprecision. We found no information on retreatment rates. Secondary outcomes: We found no evidence on serum electrolytes, 24-hour urine collection parameters or time to new stone formation. We were unable to perform any preplanned secondary analyses. Authors' conclusions Oral potassium citrate supplementation may reduce recurrent calcium urinary stone formation in children following SWL; however, our confidence in this finding is limited. A substantial number of children stopped the medication due to adverse events. There is no trial evidence on retreatment rates. There is a critical need for additional well-designed trials in children with nephrolithiasis.

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is characterized by marked dilatation of the bladder and microcolon and decreased intestinal peristalsis. Recent studies indicate that heterozygous variants in ACTG2, which codes for a smooth muscle actin, cause MMIHS. However, such variants do not explain MMIHS cases that show an autosomal recessive mode of inheritance. We performed exome sequencing in a newborn with MMIHS and prune belly phenotype whose parents are consanguineous and identified a homozygous variant (c.3598A>T: p.Lys1200Ter) in MYH11, which codes for the smooth muscle myosin heavy chain. Previous studies showed that loss of Myh11 function in mice causes a bladder and intestinal phenotype that is highly reminiscent of MMIHS. All together, these observations strongly suggest that loss-of-function variants in MYH11 cause MMIHS. The documentation of variants in ACTG2 and MYH11 thus points to the involvement of the contractile apparatus of the smooth muscle in MMIHS. Interestingly, dominant-negative variants in MYH11 have previously been shown to cause thoracic aortic aneurism and dilatation. Different mechanisms of MYH11 disruption may thus lead to distinct patterns of smooth muscle dysfunction.

Objective. To make measurable improvements in the quality and cost of neonatal intensive care using a multidisciplinary collaborative quality improvement model. Design. Interventional study. Data on treatment costs were collected for infants with birth weight 501 to 1500 g for the period of January 1, 1994 to December 31, 1997. Data on resources expended by hospitals to conduct this project were collected in a survey for the period January 1, 1995 to December 31, 1996. Setting. Ten self-selected neonatal intensive care units (NICUs) received the intervention. They formed 2 subgroups (6 NICUs working on infection, 4 NICUs working on chronic lung disease). Nine other NICUs served as a contemporaneous comparison group. Patients. Infants with birth weight 501 to 1500 g born at or admitted within 28 days of birth between 1994 and 1997 to the 6 study NICUs in the infection group (N = 2993) and the 9 comparison NICUs (N = 2203); infants with birth weight 501 to 1000 g at the 4 study NICUs in the chronic lung disease group (N = 663) and the 9 comparison NICUs (N = 1007). Interventions. NICUs formed multidisciplinary teams which worked together to undertake a collaborative quality improvement effort between January 1995 and December 1996. They received instruction in quality improvement, reviewed performance data, identified common improvement goals, and implemented “potentially better practices” developed through analysis of the processes of care, literature review, and site visits. Main Outcome Measures. Treatment cost per infant is the primary economic outcome measure. In addition, the resources spent by hospitals in undertaking the collaborative quality improvement effort were determined. Results. Between 1994 and 1996, the median treatment cost per infant with birth weight 501 to 1500 g at the 6 project NICUs in the infection group decreased from $57 606 to $46 674 (a statistical decline); at the 4 chronic lung disease hospitals, for infants with birth weights 501 to 1000 g, it decreased from $85 959 to $77 250. Treatment costs at hospitals in the control group rose over the same period. There was heterogeneity in the effects among the NICUs in both project groups. Cost savings were maintained in the year following the intervention. On average, hospitals spent $68 206 in resources to undertake the collaborative quality improvement effort between 1995 and 1996. Two thirds of these costs were incurred in the first year, with the remaining third in the second year. The average savings per hospital in patient care costs for very low birth weight infants in the infection group was $2.3 million in the post-intervention year (1996). There was considerable heterogeneity in the cost savings across hospitals associated with participation in the collaborative quality improvement project. Conclusion. Cost savings may be achieved as a result of collaborative quality improvement efforts and when they occur, they appear to be sustainable, at least in the short run. In high-cost patient populations, such as infants with very low birth weights, cost savings can quickly offset institutional expenditures for quality improvement efforts.

We evaluate our experience with the modified Cantwell-Ransley epispadias repair technique to determine the complications and long-term results.The modified Cantwell-Ransley epispadias repair was performed during the last 10 years in 93 males of whom 79 had classic bladder exstrophy and 14 had complete epispadias. Primary repair was performed in 65 boys with classic bladder exstrophy and 12 with epispadias, and secondary repair was done after prior failed reconstruction in 14 boys with classic exstrophy and 2 with complete epispadias.At mean followup of 68 months 87 patients had a horizontal or downward angled penis while standing. The incidence of urethrocutaneous fistulas was 23% in the immediate postoperative period and 19% at 3 months. A urethral stricture at the proximal anastomotic area developed in 7 patients and 5 (4 with exstrophy and 1 with epispadias) had minor skin separations of the dorsal penile skin closure. Catheterization or cystoscopy in 77 cases revealed an easily negotiable neourethral channel.The modified Cantwell-Ransley epispadias repair produces an excellent functional and cosmetic result.

Objectives. To delineate the clinical outcomes of color Doppler ultrasound (US) in the equivocal torsion patient. Methods. From 1992 to 1997, 130 patients ( Results. After clinical and radiologic evaluation, torsion was excluded in 110 patients without surgical exploration. In 3 patients, intermittent testicular torsion was diagnosed and in 17 patients, emergent exploration was performed for US diagnosis of testicular torsion. Twenty-five patients (22.7%) were subsequently lost to follow-up. Follow-up of 85 patients with US negative for torsion (mean length of follow-up = 466.9 days) revealed no testicular atrophy in 83. Two patients underwent delayed orchiectomy/contralateral orchiopexy for missed testicular torsion. Of 17 patients with US positive for torsion, 9 underwent orchiectomy for a necrotic torsed testis, 7 viable torsed testes were found, and 1 torsed appendix testis was found. Therefore, color Doppler US for the equivocal acute scrotum yielded a 1% false-positive rate, sensitivity of 88.9%, and specificity of 98.8%. Conclusion. When faced with ruling out testicular torsion, it is necessary to integrate the multiple pieces of patient data, knowing that each piece of data may have inaccuracies. With this in mind, this analysis of outcomes verifies that color Doppler US is an excellent adjunctive study in the clinically real situation in which the clinical evaluation is equivocal or low suspicion.

We assessed the impact of posterior urethral obstruction after primary bladder exstrophy closure.A review of the records of patients with classic bladder exstrophy at our institution identified 29 boys and 12 girls with a mean age of 11.75 years who had had posterior urethral outlet obstruction after closure was done in the neonatal period.Of these 41 patients 75% underwent closure elsewhere. At closure osteotomies were done in 13 patients and 23 were younger than 72 hours. Paraexstrophy skin flaps were used at primary closure in 27 cases (66%). Obstruction presented as recurrent urinary tract infection, upper tract deterioration with or without renal failure, bladder stones, difficult catheterization, urethral stitch erosion, a full bladder on ultrasound, a prolonged dry interval, urinary retention, inability to catheterize, bladder rupture, rectal prolapse and epididymitis or prostatitis. Usually the initial obstructive episode developed within 60 days of closure and it was recurrent. Therapy included suprapubic catheter placement, vesicostomy, ureterostomy, nephrostomy and multiple urethral manipulations, such as dilation with or without steroid injection, internal urethrotomy, urethral stitch removal, clean intermittent catheterization or open urethroplasty. All 6 patients who underwent long-term diversion via vesicostomy, ureterostomy or a conduit for greater than 6 months required permanent bowel segments for reconstruction, while in 5 of the 6 who underwent short-term diversion via nephrostomy or suprapubic tube placement for less than 6 months reconstruction was bowel-free. Of the 36 children in whom functional reconstruction was performed 9 are undergoing staged reconstruction, reconstruction failed in 14, 4 are socially dry and 9 are continent.Posterior urethral obstruction after exstrophy closure markedly decreases the success of staged bladder reconstruction, presents a significant risk to the upper urinary tract and should be detected early.

The NR5A1 gene encodes for steroidogenic factor 1, a nuclear receptor that regulates proper adrenal and gonadal development and function. Mutations identified by NR5A1 sequencing have been associated with disorders of sex development (DSD), ranging from sex reversal to severe hypospadias in 46,XY patients and premature ovarian failure (POF) in 46,XX patients. Previous reports have identified four families with a history of both 46,XY DSD and 46,XX POF carrying segregating NR5A1 sequence mutations. Recently, three 46,XY DSD sporadic cases with NR5A1 microdeletions have been reported. Here, we identify the first NR5A1 microdeletion transmitted in a pedigree with both 46,XY DSD and 46,XX POF. A 46,XY individual with DSD due to gonadal dysgenesis was born to a young mother who developed POF. Array CGH analysis revealed a maternally inherited 0.23 Mb microdeletion of chromosome 9q33.3, including the NR5A1 gene. Based on this finding, we screened patients with unexplained 46,XY DSD (n = 11), proximal hypospadias (n = 21) and 46,XX POF (n = 36) for possible NR5A1 copy-number variations (CNVs) via multiplex ligation-dependent probe amplification (MLPA), but did not identify any additional CNVs involving NR5A1. These data suggest that NR5A1 CNVs are an infrequent cause of these disorders but that array CGH and MLPA are useful genomic screening tools to uncover the genetic basis of such unexplained cases. This case is the first report of a familial NR5A1 CNV transmitting in a pedigree, causing both the male and female phenotypes associated with NR5A1 mutations, and the first report of a NR5A1 CNV associated with POF.

To evaluate the efficacy of needle biopsy for diagnosing Wilms tumor (WT) before chemotherapy.We reviewed our institutional experience with Tru-Cut biopsy of pediatric renal masses in patients who subsequently underwent nephrectomy. We compared biopsy pathology with nephrectomy specimens to determine if biopsy accurately predicted final pathology.Seven children underwent Tru-Cut renal mass biopsy followed by surgical resection. In 4 patients, the final biopsy pathology was definitively read as WT and in 3 subjects, the pathology was read as WT versus hyperplastic nephrogenic rest. In all 7 patients, the nephrectomy pathology confirmed a diagnosis of WT. There were no complications after biopsy, and no patients have had local or regional recurrence.In our experience, pre-therapy Tru-Cut biopsy safely provides an adequate specimen for pathologic review in diagnosing WT.

Antisperm autoanitbodies were studied in Fischer and Lewis strains of rats after either vasectomy, vasectomy followed one month later by vasovasostomy, or sham operations. The time course of antibody response to sperm protein autoantigens was assayed by Western blot analysis of sera obtained at intervals up to 3 months. Rats of both strains responded to immunization with isologous spermatozoa with production of high titer hyperimmune sera. Sera from vasectomized Fischer rats showed antisperm antibodies on Western blots, but bands were stained with less intensity and frequency than for Lewis rats. In both Fischer and Lewis strains, major protein autoantigens were observed at 75–83, 68–71, 63, 57, 51, 41, and 21–23 kDa, lending support to the hypothesis that there is a set of dominant sperm autoantigens recognized by a consensus of postvasectomy rat sera. The lesser response of Fisher rats to vasectomy was not due to absence of dominant postvasectomy sperm autoantigens in Fischer sperm extracts, nor was it attributable to inability of Fischer rats to mount an immune response to these antigens, since immunization with isologous sperm was successful in raising antibodies to the dominant autoantigens. Vasovasostomy did not result in a general decrease in antisperm antibodies, and reactions to some antigens actually increased.

Testicular torsion is one of the few emergencies in pediatric urology which requires an accurate and timely diagnosis in order to avoid testis loss. It is not an uncommon event affecting a young male population. In fact, testicular torsion is more common than testicular tumors for this same age group, yet testicular torsion has not been given the public attention it deserves as a male health risk. In this review we highlight the new information published over the past four years regarding testicular torsion. We will discuss a variety of topics associated with torsion including: medical legal issues, etiology and genetics, imaging diagnostics, innovative surgical techniques, management controversies, fertility, and new drug therapies.

Over the past 3 decades, minimally invasive stone surgery has completely overtaken open surgical approaches to upper tract pediatric urolithiasis. Progressing from least to most minimally invasive, extracorporeal shock wave lithotripsy, ureteroscopy, and percutaneous nephrolithotomy are the surgical methods of today for kidney and ureteral stones. The choice of treatment modality is individualized in children, considering patient age, stone size, number, location, and anatomic and clinical contributing factors. The purpose of this article is to review these techniques for pediatric upper urinary tract stones and summarize outcomes and complications.

Temporal patterns of IgM and IgG autoantibodies to sperm proteins were studied by western blot analysis at intervals after bilateral vasectomy, vasectomy followed one month later by vasovasostomy, or sham operations. Responses were detected to eight major autoantigens at 21-23, 36, 41, 51, 57, 63, 68-71 and 75-83 kDa, by study of staining patterns of sequential serum samples from individual animals and by analysis of the incidence of reaction to each protein. The four lower molecular weight antigens (21-23, 36, 41 and 51 kDa) provoked mainly IgG responses. The strongly stained set of higher molecular weight antigens (57, 63, 68-71 and 75-83 kDa) tended to show more clearly defined temporal patterns of IgM followed by IgG response, including a high incidence of IgM antibody at the 2-week interval. Three of the larger peptides (57, 63 and 68-71 kDa) appeared highly immunogenic, since some reactions were detected even in sham-operated rats. The classical patterns of IgM and IgG antibody responses to the majority of the dominant sperm autoantigens are in accord with the hypothesis that vasectomy mimics immunization with spermatozoa. The high incidence of IgM antibodies in the earliest sample, taken 2 weeks after vasectomy, suggests that the initial immunizing event takes place within about a week after the operation. Vasovasostomy did not bring about a decrease in antisperm antibodies. Instead, some animals demonstrated an increased reaction to certain antigens after reversal of vasectomy, even though the vasovasostomies were anatomically successful.The production of antisperm antibodies is common subsequent to vasectomy and antisperm antibodies frequently persist following the reversal of vasectomy. The number of such antibodies may even increase after vasovasostomy. Using adult male Lewis rats, the authors analyzed the dominant autoantigens which evoke IgM and/or IgG autoantibodies after vasectomy by western blotting (WB) methods, the temporal patterns of IgM and IgG autoantibodies to specific sperm proteins, and the influence of vasovasostomy upon IgM and IgG antisperm autoantibodies. The temporal patterns were studied by WB at intervals after bilateral vasectomy, vasectomy followed 1 month later by vasovasostomy, and fake operations. Responses were detected to 8 major autoantigens of 21-23, 36, 41, 51, 57, 63, 68-71, and 75-83 kDa through the study of staining patterns of sequential serum samples from individual animals and by analysis of the incidence of reaction to each protein. The 4 lower-molecular-weight antigens provoked mainly IgG responses, while the strongly stained higher-molecular-weight antigens showed more clearly defined temporal patterns of IgM followed by IgG response, including a high incidence of IgM antibody at the 2-week interval. The peptides of 57, 63, and 68-71 kDa seemed to be highly immunogenic, since some reactions were detected even in rats which received only a fake operation. Results support the hypothesis that vasectomy mimics immunization with spermatozoa, while the high incidence of IgM antibodies in the earliest sample, taken 2 weeks after vasectomy, suggests that the initial immunizing event occurs within approximately 1 week after the operation. Vasovasostomy caused no decrease in antisperm antibodies.

Nephron sparing surgery is accepted as standard of care for children with bilateral Wilms tumor or Wilms tumor in a solitary kidney and some study protocols allow nephron sparing surgery in select cases of unilateral Wilms tumor. With the increasing use of nephron sparing surgery in Wilms tumor, we reviewed pathological features from Wilms tumor radical nephrectomy specimens to determine the potential efficacy of a nephron sparing approach.Medical records of children undergoing pre-chemotherapy radical nephrectomy for unilateral Wilms tumor at our institution were reviewed. Ideal candidates for nephron sparing surgery were defined as those having a unifocal mass outside the renal hilum, sparing a third or more of the kidney, favorable histology, no signs of renal sinus or segmental vascular invasion, no metastatic lymph nodes or gross regional disease, and a distinct interface on pathological review between tumor and remaining parenchyma.A total of 78 children at a median age of 3.2 years (range 0.3 to 16.2) underwent pre-chemotherapy radical nephrectomy for unilateral Wilms tumor. Median tumor diameter was 11 cm (range 2.5 to 22). Of these children 36 (46.2%) had tumors sparing a third or more of the kidney and 70 (89.7%) had unifocal tumors. There were 73 specimens (94.6%) that showed favorable histology, and 56 (71.8%) of the specimens had a distinct border between tumor and remaining parenchyma. In total, 19 (24.4%) of the patients reviewed met all of our strict pathological criteria as ideal partial nephrectomy candidates.In a post hoc analysis using strict pathological criteria and accepted surgical oncologic principles, as many as 1 in 4 children undergoing pre-chemotherapy surgery for nonmetastatic, unilateral Wilms tumor have post-resection pathological tumor characteristics favorable for nephron sparing surgery.

Although the cause of prune belly syndrome is unknown, familial evidence suggests a genetic component. Recently 2 nonfamilial cases of prune belly syndrome with chromosome 17q12 deletions encompassing the HNF1β gene have made this a candidate gene for prune belly syndrome. To date, there has been no large-scale screening of patients with prune belly syndrome for HNF1β mutations. We assessed the role of HNF1β in prune belly syndrome by screening for genomic mutations with functional characterization of any detected mutations.We studied patients with prune belly syndrome who were prospectively enrolled in our Pediatric Genitourinary DNA Repository since 2001. DNA from patient samples was amplified by polymerase chain reaction, sequenced for coding and splice regions of the HNF1β gene, and compared to control databases. We performed functional assay testing of the ability of mutant HNF1β to activate a luciferase construct with an HNF1β DNA binding site.From 32 prune belly syndrome probands (30 males, 2 females) HNF1β sequencing detected a missense mutation (V61G) in 1 child with prune belly syndrome. Absent in control databases, V61G was previously reported in 2 patients without prune belly syndrome who had congenital genitourinary anomalies. Functional testing showed similar luciferase activity compared to wild-type HNF1β, suggesting the V61G substitution does not disturb HNF1β function.One genomic HNF1β mutation was detected in 3% of patients with prune belly syndrome but found to be functionally normal. Thus, functionally significant HNF1β mutations are uncommon in prune belly syndrome, despite case reports of HNF1β deletions. Further genetic study is necessary, as identification of the genetic basis of prune belly syndrome may ultimately lead to prevention and improved treatments for this rare but severe syndrome.

In Wilms tumor (WT), mutations in the gene encoding p53, TP53, are correlated with anaplasia; however TP53 variants have not been studied in favorable histology (FH) WTs. A single nucleotide polymorphism of TP53 encoding either arginine or proline at codon 72 is suggested to alter in vitro p53 behavior. Therefore, we analyzed tissue from 23 consecutive patients with FHWT to determine allelic and genotypic frequencies of Pro72 and Arg72 variants and correlate this with clinical outcomes. Interestingly, our cohort showed a statistically significant over-representation of the Arg allele and Arg/Arg genotype. However, the genotypic and allelic frequencies showed no significant correlation with age, stage, or disease recurrence.

Purpose A unilateral poorly or non-functioning kidney is a cause of hypertension in children. We report the outcomes of pediatric patients with unilateral renal parenchymal disease who underwent nephrectomy for hypertension. Materials and methods Consecutive hypertensive children undergoing nephrectomy with a unilateral poorly or non-functioning kidney were retrospectively reviewed; preoperative and postoperative clinical variables were analyzed. Results From July 2002 to August 2009, 21 patients (8M:13F) with average age 3.5 years and average follow-up 17.8 months were studied. Eleven patients had multicystic dysplastic kidney, 8 had reflux nephropathy, and 2 had ureteropelvic junction obstruction. Fourteen of 21 (67%) had blood pressure normalization after nephrectomy. Seven of 11 with MCDK were normotensive postoperatively compared to 6/8 patients with reflux nephropathy, and 1/2 patients with UPJ obstruction. Of the 14 patients normotensive postoperatively, 7 were on antihypertensives prior to surgery. Four of 7 patients stopped their anti-hypertensive medications postoperatively, 2 decreased from 3 and 4 medications to 1, and 1 remained on an ACE inhibitor. There were 2 patients with contralateral renal scarring, both of which remained hypertensive postoperatively. Conclusions Nephrectomy in hypertensive pediatric patients with a unilateral poorly functioning or non-functioning kidney yielded hypertension resolution in 67% (14/21), permitting cessation or diminution of antihypertensives in many patients. Given the alternative of lifelong antihypertensives with the risk of medication non-compliance and side-effects, nephrectomy is a logical option of care which can be offered to patients and families with informed knowledge of the potential for cure.