Role of a Preoperative Catheter Regimen in Achieving Early Primary Endoscopic Valve Ablation in Neonates with Posterior Urethral Valves.

PURPOSE: Primary valve ablation is preferred to vesicostomy in the initial management of posterior urethral valves. However, some neonates have a prohibitively small urethra. We describe our experience with a preoperative urethral catheter regimen to enhance the likelihood of neonatal valve ablation. MATERIALS AND METHODS: We performed a retrospective review of 126 neonates with posterior urethral valves treated between 2003 and 2019 with valve ablation prior to 10 weeks of age. The preoperative indwelling catheter either was gradually upsized to an 8Fr (progressive urethral dilation), was not upsized (nondilated) or was initially larger bore (8Fr only). The primary outcome was the ability to perform primary ablation by neonatal resectoscope. The secondary objective was to establish the parameters for considering progressive urethral dilation as well as its associated risks. RESULTS: Overall 97% could be ablated. The progressive urethral dilation group had the lowest mean weight (p <0.001). Only a larger catheter at the time of ablation was significantly associated with feasible ablation (p <0.001) and not urethral dilation, the infant's weight or his gestational age. Progressive urethral dilation was associated with a longer duration of catheterization as well as double the rate of febrile urinary tract infections (8.5%) over the nondilated group (3.6%). CONCLUSIONS: A much higher rate of primary ablation is feasible (97%) than previously reported (82%). More important than the infant's weight is whether a 6Fr to 8Fr catheter is in place at ablation. If an initial 6Fr to 8Fr catheter cannot be placed, urethral dilation to 8Fr should be performed before attempting ablation. This is both a technique and preoperative assessment that is useful for operative planning.

Assessment of health literacy in adolescents with spina bifida and their caregivers: a multi-institutional study.

INTRODUCTION: and Objective: Health literacy is defined as the ability to obtain, integrate, and appraise health-related knowledge. It is known to correlate with disparities in clinical outcomes in adults with chronic disease. Patients with spina bifida represent a potentially vulnerable cohort as they often have multiple comorbidities. The authors aimed to characterize health literacy in adolescent patients with spina bifida and their caregivers. STUDY DESIGN: The Newest Vital Sign (NVS), a validated assessment of health literacy and numeracy, was administered to patients (aged ≥10 years) and caregivers in outpatient pediatric urology and multidisciplinary spina bifida clinics. Subjects not fluent in English or Spanish and those with cognitive delay were excluded. Survey responses and demographic information were analyzed and compared between the spina bifida and control groups. RESULTS: Three hundred eleven caregivers (caregivers for patients with spina bifida: 185, caregivers for the controls: 126) and 84 adolescents (those with spina bifida: 46, controls: 38) completed the NVS. Although there was no difference in health literacy between caregivers (p = 0.98), adolescents with spina bifida demonstrated lower NVS scores (spina bifida 1 [0-3] vs. control 2 [2-4]; p = 0.02) (Figure). Health literacy of patients with spina bifida and controls increased with age (p = 0.002). Adjusting for age and gender, the odds of having limited literacy were 5.5 times higher in patients with spina bifida than in the controls (p = 0.004). Inadequate caregiver health literacy was associated with a lower education level (p < 0.001). DISCUSSION: Spina bifida is among the most complex birth defects compatible with life and affects a multitude of systems. Although it is well established that limited health literacy in adults with chronic disease is associated with adverse outcomes, there are considerably fewer data in the pediatric population. The authors found that caregivers of patients with spina bifida exhibited health literacy and numeracy comparable with parents in the control group, despite lower education levels. In contrast, adolescents with spina bifida demonstrated poorer health literacy than the controls. Multidisciplinary care is necessary, given the medical complexity of spina bifida; therefore, impaired understanding of adults' own needs may pose a barrier to successful transition to their care and subsequent outcomes. CONCLUSIONS: The majority of surveyed caregivers for patients with spina bifida exhibited adequate health literacy, especially those with some college education; however inadequate health literacy was more likely among adolescents with spina bifida when compared with the controls. Screening for health literacy may be useful to assess readiness for transition to more independent self-care among patients with spina bifida.

Opioid utilization is minimal after outpatient pediatric urologic surgery.

INTRODUCTION: There are no guidelines for opioid use after pediatric urologic surgery, and it is unknown to what extent prescriptions written for these patients may be contributing to the opioid epidemic in the United States. We sought to characterize opioid utilization in a prospective fashion following outpatient pediatric urologic surgery at our institution. MATERIALS AND METHODS: After obtainingapproval from the Institutional Review Board, we prospectively recruited pediatric patients undergoing outpatient urologic surgery. All patients and families were counseled regarding appropriate use of over-the-counter pain medications as first-line agents, with opioids for breakthrough pain only. All patients received an opioid prescription (ORx), which we attempted to standardize to 10 doses. Parents were provided with a log for keeping track of pain medication administration. Postoperative surveys were sent at various time points after surgery to assess utilization of pain medications at home. We quantified unused opioids prescribed and evaluated factors potentially associated with opioid use. RESULTS: Two hundred and two patients were recruited. All patients were male, with a median age of 2.7 years (interquartile range (IQR) 5.5, range 0.5-17.9 years). One hundred and fifty-four children underwent penile surgery, 22 underwent scrotal surgery, and 27 underwent inguinal surgery. Nearly half of our study patients were black, 33.2% were white, 12.9% were Latino, and 4.0% were Asian. The median number of doses prescribed was 10 (IQR 0, range 4.0-20.8). Postoperative surveys were completed by 80.7% of study patients. The median number of opioid doses used was 0 (IQR 2), whereas the mean was 1.28 (standard deviation (SD) 1.98). None of the factors evaluated (including patient age, surgery type, perioperative pain management techniques, length of surgery, and insurance type) were associated with the amount of opioid used at home after surgery, as utilization was equally low across all groups. DISCUSSION AND CONCLUSIONS: Ensuring adequate postoperative pain control for children is critical, yet it is also important to minimize excess ORx. We found that the majority of pediatric patients used 0-2 doses of prescription pain medication after discharge following outpatient urologic surgery, representing a small percentage of the total prescribed amount. Low utilization was seen irrespective of patient age, procedure, and perioperative factors. These data can be used to guide perioperative patient and family counseling and to guide future efforts to standardize ORx following outpatient pediatric urologic surgery.

Benign Large-cell Calcifying Sertoli Tumor of the Testis in a 13-Year-Old Male Patient Treated With Partial Orchiectomy.

Large-cell calcifying Sertoli cell tumor (LCCSCT) of the testis is an exceptionally rare lesion, found sparsely in any medical literature. There is a correlation between this entity and Peutz-Jeghers syndrome and Carney complex (40% of tumors). The remaining 60% of tumors are sporadic. A 13-year-old male patient underwent a left partial orchiectomy. Intraoperative frozen section was used, and pathology revealed a benign LCCSCT with negative margins. To our knowledge, there is not a case in the literature of an LCCSCT being treated with partial orchiectomy in a pubertal male with a normal contralateral testis.

High GMS score hypospadias: Outcomes after one- and two-stage operations.

INTRODUCTION: Established criteria to assist surgeons in deciding between a one- or two-stage operation for severe hypospadias are lacking. While anatomical features may preclude some surgical options, the decision to approach severe hypospadias in a one- or two-stage fashion is generally based on individual surgeon preference. This decision has been described as a dilemma as outcomes range widely and there is lack of evidence supporting the superiority of one approach over the other. OBJECTIVES: The aim of this study is to determine whether the GMS hypospadias score may provide some guidance in choosing the surgical approach used for correction of severe hypospadias. STUDY DESIGN: GMS scores were preoperatively assigned to patients having primary surgery for hypospadias. Those patients having surgery for the most severe hypospadias were selected and formed the study cohort. The records of these patients were reviewed and pertinent data collected. Complications requiring further surgery were assessed and correlated with the GMS score and the surgical technique used for repair (one-stage vs. two-stage). RESULTS: Eighty-seven boys were identified with a GMS score (range 3-12) of 10 or higher. At a mean follow-up of 22 months the overall complication rate for the cohort after final planned surgery was 39%. For intended one-stage procedures (n = 48) an acceptable result was achieved with one surgery for 28 patients (58%), with two surgeries for 14 (29%), and with three to five surgeries for six (13%). For intended two-stage procedures (n = 39) an acceptable result was achieved with two surgeries for 26 patients (67%), three surgeries for eight (21%), and four surgeries for three (8%). Two other patients having two-stage surgery required seven surgeries to achieve an acceptable result. Complication rates are summarized in the Table. The complication rates for GMS 10 patients were similar (27% and 33%, p = 0.28) for one- and two-stage repairs, respectively. GMS 11 patients having a one-stage repair had a significantly higher complication rate (69%) than those having a two-stage repair (29%) (p = 0.04). GMS 12 patients had the highest complication rate with a one-stage repair (80%) compared with a complication rate of 37% when a two-stage repair was used (p = 0.12). CONCLUSIONS: Guidelines to help standardize the surgical approach to severe hypospadias are needed. Staged surgery for GMS 11 and 12 patients may result in a lower complication rate but may not reduce the number of surgeries required for an acceptable result. Although further study is needed, the GMS score may be helpful for establishing such criteria.

Surgical Scar Location Preference for Pediatric Kidney and Pelvic Surgery: A Crowdsourced Survey.

PURPOSE: The benefits of minimally invasive surgery in pediatric urology, such as reduced length of hospital stay and postoperative pain, are less predictable compared to findings in the adult literature. We evaluated the choices that adult patients make for themselves and their children regarding scar location. MATERIALS AND METHODS: We surveyed the preference for scar location/size based on surgery for bladder and kidney procedures with additional questions assessing the impact of a hidden incision, length of hospital stay and pain. The survey was posted to Amazon® Mechanical Turk®. RESULTS: We analyzed a total of 954 completed surveys. Surgical history was reported in 660 surveys (69%) with scar bother reported in 357 (54.2%). For pelvic surgery the initial choice was a Pfannenstiel incision for 434 respondents (45.5%), laparoscopy port incisions for 392 (41.1%) and no preference for incision location for 126 (13.2%). When incisions were illustrated relative to undergarments, 718 respondents (75.3%) chose Pfannenstiel. For kidney surgery 567 respondents (59.4%) initially chose the dorsal lumbotomy incision, 170 (17.8%) chose a flank incision, 105 (11.0%) chose laparoscopy ports and 110 (11.5%) had no preference. Respondents were told that minimally invasive surgery might result in less pain/length of hospital stay and were asked to restate the incision choice. For pelvic surgery 232 of 434 respondents (53.5%) who had chosen Pfannenstiel and 282 of 394 (71.6%) who had chosen laparoscopy remained consistent (p <0.001). For kidney surgery 96 respondents (56.5%) who chose a flank incision, 322 (56.8%) who chose dorsal lumbotomy and 68 (64.2%) who chose laparoscopy remained consistent (p = 0.349). Agreement between the incision choice by respondent as a child and for a child was 82% (κ = 0.69) for pelvic surgery and 84.6% (κ = 0.75) for kidney surgery. CONCLUSIONS: The smallest incision is not always the patient preferred incision, particularly in childhood when pain, length of hospital stay and blood loss may be equivocal among approaches. Discussion of surgical treatment options should include scar length, location and relationship to undergarments.

Antitumor activity of sulfated hyaluronic acid fragments in pre-clinical models of bladder cancer.

Tumor cell-derived hyaluronidase HYAL-1 degrades hyaluronic acid (HA) into angiogenic fragments (AGF: 10-12 disaccharides). AGF support tumor growth and progression. Urine and tissue HAase/HYAL-1 levels are sensitive markers for high-grade bladder cancer (BCa) and its metastasis. In preclinical models of BCa, we evaluated whether o-sulfated AGF (sHA-F) inhibits HAase activity and has antitumor activity. At IC50 for HAase activity inhibition (5-20 µg/ml [0.4-1.7 µM]), sHA-F significantly inhibited proliferation, motility and invasion of HYAL-1 expressing BCa cells (253J-Lung, HT1376, UMUC-3), P<0.001. sHA-F did not affect the growth of HYAL-1 non-expressing BCa (5637, RT4, T24, TCCSUP) and normal urothelial (Urotsa, SV-HUC1) cells. sHA-F treatment induced apoptosis by death receptor pathway. sHA-F downregulated transcript and/or protein levels of HA receptors (CD44, RHAMM), p-AKT, ß-catenin, pß-Catenin(S552), Snail and Twist but increased levels of pß-Catenin(T41/S45), pGSK-3α/ß(S21/S9) and E-cadherin. sHA-F also inhibited CD44/Phosphoinositide 3-kinase (PI-3K) complex formation and PI-3K activity. AGF addition or myristoylated-AKT overexpression attenuated sHA-F effects. Contrarily, HYAL-1 expression sensitized RT4 cells to sHA-F treatment. In the 253J-L and HT1376 xenograft models, sHA-F treatment significantly inhibited tumor growth (P<0.001), plausibly by inhibiting angiogenesis and HA receptor-PI-3K/AKT signaling. This study delineates that sHA-F targets tumor-associated HA-HAase system and could be potentially useful in BCa treatment.

Magnetic resonance urography for diagnosis of pediatric ureteral stricture.

PURPOSE: Ureteral stricture is a rare cause of hydronephrosis in children and is often misdiagnosed on ultrasound (US) and diuretic renal scintigraphy (DRS), requiring intraoperative diagnosis. We evaluated ureteral strictures diagnosed by magnetic resonance urography (MRU) at our institution. MATERIALS AND METHODS: Children with ureteral stricture who underwent MRU were identified. Patient demographics, prior imaging, MRU findings, and management were assessed. The efficacy of MRU in diagnosis of stricture was compared with US and DRS. Patients with ureteropelvic or ureterovesical junction obstruction were excluded. RESULTS: Twenty-eight ureteral strictures diagnosed by MRU between 2003 and 2013 were identified; 22% of strictures were diagnosed by DRS ± US. The mean age at MRU diagnosis was 2.4 years (range 4 weeks-15 years). Hydronephrosis was the most common presentation, accounting for 20 (71%) cases. Other etiologies included pain (3), incontinence (2), and urinary tract infection, cystic kidney, and absent kidney, present in one case each. A mean of 2.7 imaging studies was obtained prior to MRU diagnosis. Twenty-one (75%) ureteral strictures required surgical intervention, with the approach dependent upon location. CONCLUSIONS: MRU provides excellent anatomic and functional detail of the collecting system, leading to accurate diagnosis and management of ureteral stricture in children.

Functional supernumerary testis in a child with testicular torsion and review of polyorchidism.

Histologically confirmed polyorchidism is an uncommon condition. The majority of cases are asymptomatic and associated with inguinal hernia or cryptorchidism. There are few reported cases of pediatric supernumerary testis presenting with testicular torsion. We present a case of missed torsion with incidentally detected triorchidism as well as an overview of pediatric polyorchidism.

Emergency room visits and readmissions after pediatric urologic surgery.

OBJECTIVE: Reducing readmissions has become a focal point to increase quality of care while reducing costs. We report all-cause unplanned return visits following urologic surgery in children at our institution. MATERIALS AND METHODS: Children undergoing urology procedures with returns within 30 days of surgery were identified. Patient demographics, insurance status, type of surgery, and reason for return were assessed. RESULTS: Four thousand and ninety-seven pediatric urology surgeries were performed at our institution during 2012, with 106 documented unplanned returns (2.59%). Mean time from discharge to return was 5.9 ± 4.9 days (range, 0.3-24.8 days). Returns were classified by chief complaint, including pain (32), infection (30), volume status (14), bleeding (11), catheter concern (8), and other (11). Circumcision, hypospadias repair, and inguinal/scrotal procedures led to the majority of return visits, accounting for 21.7%, 20.7%, and 18.9% of returns, respectively. Twenty-two returns (20.75%) resulted in hospital readmission and five (4.72%) required a secondary procedure. Overall readmission rate was 0.54%, with a reoperation rate of 0.12%. CONCLUSIONS: The rate of unplanned postoperative returns in the pediatric population undergoing urologic surgery is low, further strengthening the argument that readmission rates in children are not necessarily a productive focal point for financial savings or quality control.

Selective endoscopic treatment of the non-refluxing contralateral ureter prevents new contralateral vesicoureteral reflux.

OBJECTIVE: The objective of this study was to evaluate risk factors for new contralateral vesicoureteral reflux (NCVUR) and to investigate whether assessment of the non-refluxing contralateral ureter (NRCU) by hydrodistention and selective treatment can reduce the incidence of NCVUR. MATERIALS AND METHODS: From 2001 to 2007, 339 of 841 patients (40%) were treated for unilateral VUR by endoscopic injection. While in the first 267 patients the NRCU was only assessed by hydrodistention but not injected (observation group), NRCUs of the subsequent 72 patients were prophylactically treated if deemed at high risk for NCVUR (H2 or H3) (prophylaxis group). RESULTS: NCVUR occurred in 30 of 267 patients (11.2%) whose NRCUs were observed. No statistically significant risk factors for NCVUR were found in this group. In the subsequent 72 patients, whose H2 and H3 ureters were selectively injected (N = 56), no cases of NCVUR were seen. CONCLUSIONS: Prophylactic endoscopic treatment of NRCU H2 and H3 ureters successfully prevented the occurrence of NCVUR.

Clinical and radiographic results of endoscopic injection for vesicoureteral reflux: defining measures of success.

OBJECTIVE: Criteria for success following endoscopic vesicoureteral reflux (VUR) surgery vary greatly. We sought to define outcomes based on radiographic and long-term clinical follow up. METHODS: We reviewed the charts and interviewed parents of children who underwent endoscopic treatment for primary VUR (grades I-IV). All patients had a postoperative voiding cystourethrogram (VCUG) at mean of 3 months (1-21 months) and all cases of postoperative febrile urinary tract infection (FUTI) prompted repeat VCUG. Radiographic success was defined as no VUR on postoperative VCUG and clinical success as no FUTIs during follow up of 12-36 months. To demonstrate how criteria for success can affect outcomes, we calculated the success rates using different definitions. RESULTS: In 2004-2008, 336 patients (296 female and 40 male, mean age 4 years) were treated with dextranomer/hyaluronic acid via the Double-HIT method. Initial radiographic success was 90% (302/336). Of these, 19 (6%) developed FUTIs, 12 (4%) of whom had recurrent VUR, and 5 (2%) went on to open surgery. Of the radiographic failures, 18% were observed with no further treatment. Success defined clinically was 94% (281/300), and as 'radiographic cure and no clinical evidence of FUTIs' it was 82% (275/336). CONCLUSIONS: It is important to agree on a universal definition of success for VUR interventions to compare across studies and across therapies. Clinical success is more meaningful to the patient, and initial radiographic success could be followed by UTI necessitating further intervention. We question the need for routine postoperative VCUG.

Differentiation of human mesenchymal stem cell spheroids under microgravity conditions.

To develop and characterize a novel cell culture method for the generation of undifferentiated and differentiated human mesenchymal stem cell 3D structures, we utilized the RWV system with a gelatin-based scaffold. 3 × 10(6) cells generated homogeneous spheroids and maximum spheroid loading was accomplished after 3 days of culture. Spheroids cultured in undifferentiated spheroids of 3 and 10 days retained expression of CD44, without expression of differentiation markers. Spheroids cultured in adipogenic and osteogenic differentiation media exhibited oil red O staining and von Kossa staining, respectively. Further characterization of osteogenic lineage, showed that 10 day spheroids exhibited stronger calcification than any other experimental group corresponding with significant expression of vitamin D receptor, alkaline phosphatase, and ERp60 . In conclusion this study describes a novel RWV culture method that allowed efficacious engineering of undifferentiated human mesenchymal stem cell spheroids and rapid osteogenic differentiation. The use of gelatin scaffolds holds promise to design implantable stem cell tissue of various sizes and shapes for future regenerative treatment.

Pediatric chronic orchalgia.

INTRODUCTION: Chronic orchalgia, defined as testicular pain lasting > 3 months and interfering with normal activities, is neglected in the pediatric literature. We describe our experience with the evaluation and treatment of pediatric chronic orchalgia patients. MATERIALS AND METHODS: Charts were screened to identify patients meeting the criteria for chronic orchalgia. Charts were further reviewed to record the history and physical exam, diagnostic tests, treatment and outcomes. RESULTS: 65/982 patients met the criteria for chronic orchalgia. Mean age was 13 and mean duration of pain was 8.6 months. Physical exam findings were normal in 46 patients (70%). 59 patients were managed conservatively with resolution (10/59, 17%) or a single visit (36/59, 61%) in 78%. 13/59 (22%) patients showed either minor improvement or no change in symptoms. 5 non-responding patients were managed by the anesthesia pain service; 4 received epidurals with or without additional oral pain medications with 3 experiencing significant pain improvement. CONCLUSION: Conservative management of chronic orchalgia allowed symptoms to subside in the majority of cases. We recommend patients be treated with conservative measures for 1-2 months. If this fails, early involvement of the anesthesia pain service can offer treatment modalities such as epidural analgesia. Surgical management in the face of a normal physical exam does not seem to have a role.

Targeting hyaluronidase for cancer therapy: antitumor activity of sulfated hyaluronic acid in prostate cancer cells.

The tumor cell-derived hyaluronidase (HAase) HYAL-1 degrades hyaluronic acid (HA) into proangiogenic fragments that support tumor progression. Although HYAL-1 is a critical determinant of tumor progression and a marker for cancer diagnosis and metastasis prediction, it has not been evaluated as a target for cancer therapy. Similarly, sulfated hyaluronic acid (sHA) has not been evaluated for biological activity, although it is an HAase inhibitor. In this study, we show that sHA is a potent inhibitor of prostate cancer. sHA blocked the proliferation, motility, and invasion of LNCaP, LNCaP-AI, DU145, and LAPC-4 prostate cancer cells, and induced caspase-8-dependent apoptosis associated with downregulation of Bcl-2 and phospho-Bad. sHA inhibited Akt signaling including androgen receptor (AR) phosphorylation, AR activity, nuclear factor κB (NFκB) activation, and VEGF expression. These effects were traced to a blockade in complex formation between phosphoinositide 3-kinase (PI3K) and HA receptors and to a transcriptional downregulation of HA receptors, CD44, and RHAMM, along with PI3K inhibition. Angiogenic HA fragments or overexpression of myristoylated Akt or HA receptors blunted these effects of sHA, implicating a feedback loop between HA receptors and PI3K/Akt signaling in the mechanism of action. In an animal model, sHA strongly inhibited LNCaP-AI prostate tumor growth without causing weight loss or apparent serum-organ toxicity. Inhibition of tumor growth was accompanied by a significant decrease in tumor angiogenesis and an increase in apoptosis index. Taken together, our findings offer mechanistic insights into the tumor-associated HA-HAase system and a preclinical proof-of-concept of the safety and efficacy of sHA to control prostate cancer growth and progression.