Urologic Presentation of Unicentric Pediatric Castleman Disease in the Setting of Acute Renal Colic.

An 11-year-old otherwise healthy female presented with renal colic and during computed tomography imaging evaluation, she was found to have a right distal ureteral stone with associated hydroureteronephrosis, medially deviated ureter, and 4-cm solid retroperitoneal mass. The mass was palpable on physical exam and was further categorized with magnetic resonance imaging, ultrasound, and laboratory testing. A multidisciplinary team approach, including pediatric surgery, radiology, oncology, and urology, led to the patient undergoing a right retrograde pyelogram, ureteroscopy with stent placement, and laparoscopic excision of retroperitoneal mass. Her pathology revealed lymphoid hyperplasia with histologic features of Castleman disease.

Decisional conflict in American parents regarding newborn circumcision.

BACKGROUND: Decisional conflict surrounding the topic of circumcision in the newborn male is assumed in some parents but has not been quantified or qualified. It is known that parents often base their decision on cultural and social factors and that physician discussions do affect ultimate decision-making. Information on parents' decision-making surrounding newborn circumcision and ways to mitigate conflict or uncertainty around the decision-making process is needed to better counsel them appropriately. OBJECTIVES: To identify the presence or absence of decisional conflict in parents-to-be deciding whether or not to circumcise their child as well as to identify determinants of this conflict to direct future educational measures. STUDY DESIGN: Parents presenting to obstetrics clinic as well as contacted by institutional email were recruited using convenience sampling and completed the validated Decisional Conflict Scale (DCS). A smaller subset of subjects were recruited via institutional email to complete semi-structured interviews regarding the decision-making process and specifically uncertainty regarding the decision. Descriptive statistics and unpaired t tests were used for analysis of survey data. For interview data, an iterative, grounded theory methodology was used. RESULTS: 173 subjects completed the DCS. 12% of all participants had high decisional conflict. Intuitively, those who had not yet decided whether to circumcise had the highest proportion of high DCS (69%), followed by those who had decided to circumcise (9.3%) and those who had decided not to circumcise (1.7%). 24 subjects were interviewed, and based on their DCS scores and interview responses were classified as low, intermediate and high conflict. Three primary themes emerged delineating the high from low conflict groups. There were notable differences in the feelings of subjects regarding knowledge and feeling informed, the importance of particular values and clarity of the roles of these values in decision-making, and feelings of supported decision-making. These themes were used to create a visual model depicting the individual needs of each decision-maker (Fig. 1). DISCUSSION: This study highlights the need for decision support for parents that is not only information-based but focuses on values clarity and supported decision-making. This study provides a jumping-off point for creation of shared decision-making tools directed at individual needs. The limitations of this study are a single institution design and homogeneous population, so when designing materials, additional unrecognized needs will likely be identified. CONCLUSION: A small, but real proportion of parents-to-be experience significant uncertainty around the decision to circumcise their newborn boys. Identified needs of parents include feeling informed, feeling supported and clarification of important values related to the problem.

What is the angle of a banana? The difficulty in reliable assessment of hypospadias chordee.

INTRODUCTION: The degree of chordee associated with hypospadias impacts operative management. Unfortunately, poor inter-observer reliability in assessing chordee by multiple methods in vitro has been demonstrated. This variability may be related to the fact that chordee is not a discrete angle, but rather an arc-like curvature similar to that of a banana. On an attempt to improve this variability, we assessed the inter-rater reliability of a novel method of chordee measurement and compared it to measurements with a goniometer both in vitro and in vivo. MATERIALS AND METHODS: In vitro assessment of curvature was performed using 5 bananas. In vivo chordee measurement was performed during 43 hypospadias repairs. On in vitro and in vivo cases, chordee was assessed independently by faculty and resident physicians. Angle assessment was performed in a standard manner with a goniometer and with a smartphone app using ruler measurements of the length and width of the arc (Summary Figure). The proximal and distal aspect of the arc to be measured was marked on the bananas, whereas the penile measurements were taken from the penoscrotal to the sub-coronal junctions. RESULTS: In vitro banana assessment demonstrated strong intra- and inter-rater reliability for length (0.89 and 0.88, respectively) and width measurements (0.97 and 0.96). The calculated angle demonstrated an intra- and inter-rater reliability of 0.67 and 0.67. The banana goniometer/protractor measurements were weak with an intra-rater and inter-rater reliability of 0.33 and 0.21. With hypospadias chordee, the inter-rater reliability was strong for length and width measurements (0.95 and 0.94) and 0.48 for calculated angle. The inter-rater reliability of the goniometer angle was 0.96. Further assessment of inter-rater goniometer reliability was performed relative to degree of chordee as characterized by faculty. The inter-rater reliability for ≤15°, 16-30, and ≥30° was 0.68 (n = 20), 0.34 (n = 14), and 0.90 (n = 9), respectively. When the goniometer angle was classified as ≤15, 16-30, or ≥30° by one physician, it was classified outside of this range by the other physician 23%, 47%, and 25% of the time, respectively. DISCUSSION: Our data demonstrate significant limitations of the goniometer for assessing chordee in vitro and in vivo. We were unable to demonstrate significant improvement in chordee assessment using arc length and width measurements to calculate radians. CONCLUSIONS: Reliable and precise techniques for measuring hypospadias chordee remain elusive and draw into question the validity and usability of management algorithms employing discrete values.

The utility of renal medullary pyramidal thickness measurements on the first and second postnatal ultrasound in infants with congenital hydronephrosis.

INTRODUCTION: Prior studies with postnatal ultrasound measurements of the medullary pyramid thickness (PT) demonstrate a PT < 3 mm as a significant risk factor for the diagnosis of UPJ obstruction and pyeloplasty. These studies used the postnatal ultrasound demonstrating the largest degree of hydronephrosis. Since early identification of children at increased risk of obstruction and pyeloplasty would be clinically useful, we reviewed the PT on the first and second postnatal ultrasound in infants with congenital hydronephrosis. OBJECTIVE: The aims of the study were to determine the prognostic value of: 1) PT on the first and second postnatal ultrasound, 2) a change in PT between first and second ultrasounds, and 3) ratio of PT in the hydronephrotic kidney to the contralateral PT in the normal kidney in those with unilateral hydronephrosis. We hypothesized that a smaller PT on either the first or second ultrasound, as well as a decreasing PT between the first and second ultrasound, and a decreased ratio of hydronephrotic PT to the contralateral normal kidney, would each be early predictors of subsequent pyeloplasty. STUDY DESIGN: A retrospective chart and ultrasound review of children with a diagnosis of isolated high grade (SFU grade 3 or 4) hydronephrosis was performed. This study also analyzed the impact on predictive ability of the PT obtained on an ultrasound obtained before 3 days of life compared to those in which the first ultrasound was obtained after 3 days of life. 91 infants (77 boys and 14 girls) met eligibility criteria (105 kidneys). The median age (IQR) at first ultrasound was 1.5 (1.0-15.0) days and 54.0 (27.5-123.0) days at the second ultrasound. DISCUSSION AND CONCLUSION: For the group overall, a smaller PT on both the first and second ultrasound was associated with increased risk of pyeloplasty, however, a PT obtained on an ultrasound prior to 3 days of life was not demonstrated to be predictive. Of note, PT was predictive in this same group of patients on their second ultrasound. A PT of <3 mm on an ultrasound obtained beyond 3 days of life was associated with higher risk of pyeloplasty. The PT ratio of hydronephrotic to normal contralateral kidney of the children who had their first ultrasound after 3 days of life was also significant in predicting the odds of having surgery. In addition, a decreasing PT between the first and second ultrasound was also identified as a risk factor for pyeloplasty.

Robot assisted laparoscopic partial cystectomy for inflammatory myofibroblastic tumor with simultaneous intraoperative flexible cystoscopy for tumor mapping.

Bladder masses are an infrequent occurrence rarely suspected in cases of pediatric hematuria. Inflammatory myofibroblastic tumors represent one differential diagnosis that is difficult to characterize as purely benign and should therefore be given special consideration. Although uncommon, this is an important entity to recognize for potential bladder sparing and minimally invasive surgical approaches.

Papers presented at the fall 2020 Pediatric Urologic Oncology Work Group of the Societies of Pediatric Urology meetingNeonatal Serum Electrolyte and Proteinuria Screening on 46,XY Ambiguous Genitalia Patients May Allow Early Diagnosis of Denys-Drash Syndrome: A Case Report.

A term infant with prenatally noted ambiguous genitalia and nonpalpable gonads presented with life-threatening hyponatremia, hypertension, acidosis, and anuric renal failure requiring peritoneal dialysis at age 3 months.Sequencing confirmed 46, XY Denys-Drash syndrome (DDS) due to heterozygous Wilms tumor-1 exon 8 mutation encoding p.His445Arg. Renal US identified bilateral multifocal renal masses at age 8 months. Bilateral retroperitoneal nephrectomies found bilateral nephroblastomatosis without Wilms' tumor avoiding chemotherapy, followed by bilateral laparoscopic orchiopexies. We suggest monthly screening of 46, XY DSD cases for DDS by evaluating for proteinuria and electrolyte disarray starting at diagnosis of DSD to prevent acute life-threatening renal failure presentation.

Renal artery angiography in pediatric trauma using a national data set.

INTRODUCTION: With limited pediatric renal trauma management literature, treatment pathways for children have been extrapolated from the adult population. A shift to non-operative management has led to higher renal preservation rates; however, characterization of endovascular intervention in the pediatric trauma population is lacking. OBJECTIVE: This study uses the National Trauma Data Bank (NTDB), to evaluate renal outcomes after use of renal artery angiography. We hypothesized that patients undergoing renal artery angiography for renal trauma are unlikely to require additional surgical interventions. STUDY DESIGN: All children ≤18 years old treated for traumatic renal injuries from 2012 to 2015 were identified by the Abbreviated Injury Scaled Score (AISS) codes in the NTDB. AISS codes were converted to American Association for Surgery of Trauma (AAST) grades. ICD-9 codes were used to identify patients that had renal artery angiography, and additional renal interventions such as nephrectomy, partial nephrectomy, percutaneous nephrostomy tube or ureteral stent placement. RESULTS: 536,379 pediatric trauma cases were in the NTDB from 2012 to 2015, with 4506 renal injury cases identified. A total of 88 patients had renal artery angiography (ICD-9 88.45). Only 10% (n = 9) of patients who received renal artery angiography underwent an additional urological intervention. Of those nine, two patients were excluded due to renal angiography taking place after nephrectomy was performed. The remaining seven patients had high grade laceration (AAST grade 4-5). Overall, two patients underwent post angiography nephrectomies, two patients had partial nephrectomies, one percutaneous nephrostomy tube was placed (prior to partial nephrectomy), one aspiration of a kidney (prior to ureteral stent placement), and three had ureteral stent placements. DISCUSSION: The limitations of this study include: the NTDB is a national dataset that is not population based, inclusion is limited to the first hospitalization, inaccuracies exist in encounter coding, and the database is lacking laterality of the renal injury. Based on nonspecific nature of ICD-9 coding for angioembolization, we are unable to discern the number of cases that subsequently had angioembolization after or at the time of angiography. CONCLUSION: Renal artery angiography in children remains a rare procedure, 88/4,506, in children with renal trauma. In pediatric trauma cases that undergo renal artery angiography additional procedures are more common with higher grade injuries. Further studies are needed to create pediatric specific trauma management algorithms.

Renal ultrasound to evaluate for blunt renal trauma in children: A retrospective comparison to contrast enhanced CT imaging.

INTRODUCTION: The standard imaging modality for hemodynamically stable blunt abdominal trauma patients is a contrast enhanced CT scan, which is reflected in the current AUA urotrauma guidelines. This comes, however, with radiation exposure and the potential sequalae of IV contrast administration in the pediatric patient. OBJECTIVE: We hypothesize that ultrasound imaging would be able to diagnose and rule out clinically significant renal injuries when compared to the gold standard of CT scan in the setting of pediatric blunt abdominal trauma. STUDY DESIGN: All children <18 years of age who were evaluated for blunt abdominal trauma who had a CT scan and ultrasound imaging of kidneys were identified. The ultrasound images were reviewed by four reviewers who were blinded to CT results and all clinical information. The ability of ultrasound to diagnose and rule out clinically significant renal injury was evaluated by diagnostic test performance characteristics including sensitivity, specificity, negative predictive value and positive predictive value. RESULTS: There were 76 patients identified, 24 of which had a renal injury (1 bilateral) diagnosed by CT scan for a total of 25 injuries in 152 renal units. There were six grade I-II injuries and 19 grade III-V injuries. The sensitivity of the four blinded reviewers by ultrasound alone to detect the 19 grade III-V injuries ranged from 79 to 100% with NPV between 97 and 100%. Three of the four reviewers identified all 19 grade III-V injuries by ultrasound. When combined with significant hematuria, all 19 grade III-IV injuries were identified. Of note, all patients with a grade III-V injury of the kidney had significant hematuria. Of the grade I-II renal injuries, all reviewers identified 1/5 or 2/5 by ultrasound alone. DISCUSSION: The limitations of this study include: its retrospective nature, limited number of patients and reviewers, quality of the ultrasound machine. and experience of technologist, radiologist and urologist. A major limitation is the inability to assess other solid organ injuries during this initial study. CONCLUSIONS: When compared to a CT scan as the gold standard, kidney ultrasound images had a sensitivity of 79-100% to detect grade III-V injuries and NPV of 97-100% by four blinded reviewers. All grade III-V injuries had either an episode of gross hematuria or microscopic hematuria >50 RBC/hpf. A prospective study that includes full abdominal imaging is needed to confirm that ultrasound can safely be used in place of CT scan for evaluation of hemodynamically stable blunt trauma patients.

Prune belly syndrome in surviving males can be caused by Hemizygous missense mutations in the X-linked Filamin A gene.

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 ß-integrin 1 (ITGß1). 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.

Early Vs. Expectant Management of Spina Bifida Patients-Are We All Talking About a Risk Stratified Approach?

PURPOSE OF REVIEW: Advancements in the care of patients affected by myelomeningocele have flourished in recent years especially with respect to renal preservation and continence. Involvement of urologists both prenatally and early in life has driven many developments in preventative care and early intervention. As of yet, however, the ideal management algorithm that offers these patients the least invasive diagnostic testing and interventions while still preserving renal and bladder function remains ill defined. RECENT FINDINGS: In a shift from prior years where the use of surgical intervention and intermittent catheterization were more liberally employed, some providers have more recently advocated for monitoring patients in a more conservative manner with a variety of diagnostic tests until radiographic or clinical changes are discovered. The criteria used to define the need for catheterization and the timing to initiate CIC or more invasive interventions is disparate across pediatric urology and there is published data to support several approaches. This review presents some of these criteria for use of CIC and some newer evidence to support different approaches along with supporting the trend toward individualized medicine and use of risk stratification in developing clinical treatment algorithms.

Managing vesicoureteral reflux in children: making sense of all the data.

Current management of vesicoureteral reflux (VUR) in children is the result of a steady albeit controversial evolution of data and thinking related to the clinical impact of VUR and urinary tract infection (UTI) in children, the value of clinical screening, and the relative impact of testing and interventions for VUR. While controversy continues, there is consensus on the importance of bladder dysfunction on VUR outcomes, the likelihood of VUR resolution, and the fact that not all children with VUR require active treatment. Early efforts to define risk stratification hold the most promise to provide more patient-specific treatment of UTI and VUR in children.

miR-301a expression: Diagnostic and prognostic marker for prostate cancer.

BACKGROUND: Prostate-specific antigen screening for prostate cancer (CaP) remains controversial. This study establishes the role of microRNA 301a (miR-301a) as a supplemental biomarker that can distinguish between patients with benign prostate hyperplasia and clinically significant CaP. We evaluate the ability of miR-301a to predict the adverse pathology of CaP. METHODS: In the first cohort, serum and prostate tumor samples were obtained from thirteen patients with Benign prostate hyperplasia (BPH), twelve patients with Gleason 6, and sixteen patients with Gleason 7 prostate adenocarcinoma. In the second cohort, 40 prostatectomy cases were selected (BPH:12, Gleason 6:12 and Gleason 7:16). MiRNA was extracted from serum and tumor samples. Quantitative reverse transcription-polymerase chain reaction was performed for detection of miR-301a. To understand the molecular role of miR-301a, we performed cell viability, Western blots, promoter analysis, overexpression, and silencing studies in BPH and DU-145 cell lines. RESULTS: MiR-301a demonstrated a significantly higher expression in both serum and tumor tissue in patients with CaP when compared to patients with BPH (P = 0.011 and 0.013 for serum and tissue expression, respectively). Expression of miR-301a in prostatectomy specimens correlated with increased Gleason score. We demonstrated that miR-301a inhibited the pro-apoptotic function of RUNX3, and activated ROCK1-mediated pro-survival signal in CaP. Silencing miR-301a initiated the pro-apoptotic function of RUNX3 by inhibiting ROCK1 expression in CaP cells. CONCLUSIONS: Expression of miR-301a could be a valuable adjunct tool for stratifying patients with elevated prostate-specific antigen, as well as those diagnosed with CaP. Including the miR-301a as an additional variable in MSKCC post-prostatectomy nomogram improved its ability in facilitating clinical decision-making.

Activation of AKT negatively regulates the pro-apoptotic function of death-associated protein kinase 3 (DAPK3) in prostate cancer.

The activation of AKT governs many signaling pathways and promotes cell growth and inhibits apoptosis in human malignancies including prostate cancer (CaP). Here, we investigated the molecular association between AKT activation and the function of death-associated protein kinase 3 (DAPK3) in CaP. An inverse correlation of pAKT and DAPK3 expression was seen in a panel of CaP cell lines. Inhibition of AKT by wortmannin/LY294002 or overexpression of DAPK3 reverts the proliferative function of AKT in CaP cells. On the other hand, ectopic expression of AKT inhibited DAPK3 function and induced proliferation of CaP cells. In addition, AKT over-expressed tumors exhibit aggressive growth when compared to control vector in xenograft models. The immunohistochemistry results revealed a down-regulation of DAPK3 expression in AKT over-expressed tumors as compared to control tumors. Finally, we examined the expression pattern of AKT and DAPK3 in human CaP specimens - the expected gradual increase and nuclear localization of pAKT was seen in higher Gleason score samples versus benign hyperplasia (BPH). On the contrary, reduced expression of DAPK3 was seen in higher Gleason stages versus BPH. This suggests that inhibition of DAPK3 may be a contributing factor to the carcinogenesis of the prostate. Understanding the mechanism by which AKT negatively regulates DAPK3 function may suggest whether DAPK3 can be a therapeutic target for CaP.

Expression of urokinase-type plasminogen activator (uPA), its receptor (uPAR), and inhibitor (PAI-1) in human breast carcinomas and their clinical relevance.

Serine proteases convert plasminogen to plasmin which is involved in tissue remodeling under physiologic and pathophysiologic conditions, including breast carcinoma invasion and progression. Both urokinase-type plasminogen activator (uPA) and pro-uPA associate with uPA receptor (uPAR) on target cells, where plasminogen activator inhibitors (e.g., PAI-1) may modulate their activities. Expression levels of these factors were compared in breast carcinomas relative to patient characteristics, carcinoma features, and clinical outcome. uPA, uPAR, and PAI-1 were quantified by enzyme-linked immunosorbent assay (ELISA) in extracts of 226 biopsies while estrogen receptor (ER) and progestin receptor (PR) were determined by enzyme immunoassay (EIA) or radio-ligand binding. Each set of assays contained a novel reference specimen with known quantities of each of these five analytes. Levels in ng/mg protein of these biomarkers exhibited ranges: uPA (0-12.3); uPAR (0-19.5); PAI-1 (0-91.2). When considered independently, expression of uPA, uPAR, or PAI-1 was unrelated to patient age or menopausal status. Although no correlation was observed between each analyte with stage, grade, or ER/PR status, levels appeared to differ with pathology and nodal status. A dendrogram from hierarchical clustering of uPA, uPAR, and PAI-1 levels in 106 specimens revealed three clusters of breast cancer patients. Kaplan-Meier analyses of uPA, uPAR, and PAI-1 indicated a correlation with overall survival (OS), suggesting collective examination of these biomarkers is useful in predicting clinical outcome of breast cancer.