Dr. Hsi-Yang Wu is a board certified Pediatric Urologist who treats all aspects of pediatric urology. He has a special interest in urinary incontinence and complex urinary reconstruction related to neurogenic bladder, renal transplantation and bladder exstrophy, as well as kidney stones and pediatric urologic oncology. He is the program director for the Pediatric Urology fellowship at Lucile Packard Children's Hospital and enjoys teaching the art of caring for children and their families.

Administrative Appointments

  • Program Director, Pediatric Urology Fellowship (2009 - Present)

Honors & Awards

  • Magna cum laude, Harvard College (1989)
  • American Foundation for Urologic Disease Summer Student Scholarship, University of Pennsylvania (1990)
  • Pfizer Scholars in Urology, UCSF (1998)
  • Arline and Pete Harman Endowed Faculty Scholar, Stanford University (2012)

Professional Education

  • A.B., Harvard College, Chemistry (1989)

Current Research and Scholarly Interests

I am interested in how the brain matures to control the bladder and external sphincter to achieve urinary continence. Using functional MRI of the brain, we are investigating if certain patterns of activity will predict which children will respond to therapy for incontinence.

2023-24 Courses

Graduate and Fellowship Programs

  • Pediatric Urology (Fellowship Program)

All Publications

  • Ureterostomy as an alternative to ileal conduits in pediatric kidney transplantation. Clinical transplantation Brubaker, A. L., Wu, H., Lee, A., Vuong, P., Stoltz, D. J., Chaudhuri, A., James, G., Grimm, P. C., Concepcion, W., Gallo, A. E. 2020: e13777


    INTRODUCTION: Urinary diversion in pediatric renal transplant candidates with bladders not amenable to primary reconstruction can be achieved by pre-transplant ileal conduit creation. We performed cutaneous ureterostomies to limit pre-transplant surgery, protect the peritoneum for dialysis, transplant patients sooner, and preserve ureter length for future surgical reconstruction.METHODS: We compared four pediatric transplant recipients with ureterostomies to four recipients with ileal conduits from 2009-2017.RESULTS: All patients with ileal conduits developed at least one urinary tract infection (UTI) within one year of transplant and three of four patients had recurrent UTIs within the first year. Two patients required ileal conduit revisions for redundant conduits and recurrent UTIs. Of the four ureterostomy patients, two patients had UTIs within one year of transplant. Two patients developed ureterostomy strictures requiring revision at the fascial level; one was associated with a UTI.CONCLUSION: In our small case series, ureterostomy allowed for a single operative intervention with preservation of ureter length for later reconstruction. Ureterostomy is safe and recurrent UTI may be lower in the ureterostomy group. Long-term evaluation of ureterostomy for urinary diversion in pediatric kidney transplant is warranted.

    View details for DOI 10.1111/ctr.13777

    View details for PubMedID 31904131

  • When does vesicoureteral reflux in pediatric kidney transplant patients need treatment? Pediatric transplantation Wu, H., Concepcion, W., Grimm, P. C. 2018: e13299


    PURPOSE: The treatment of VUR in children with UTI has changed significantly, due to studies showing that antibiotic prophylaxis does not decrease renal scarring. As children with kidney transplants are at higher risk for UTI, we investigated if select patients with renal transplant VUR could be managed without surgery.MATERIALS AND METHODS: A total of 18 patients with VUR into their renal grafts were identified, and 319 patients underwent transplantation from 2006 to 2016. The cause for the detection of the VUR, treatment, and graft function was reviewed.RESULTS: Six boys and 12 girls were identified, 13 of whom had grade 3 or 4 VUR into the renal graft. Nine patients presented with hydronephrosis or abnormal renal biopsy: eight were successfully managed with antibiotic prophylaxis and bladder training, one developed UTI and underwent Dx/HA subureteric injection. Nine patients presented with recurrent febrile UTI, only one was successfully managed without surgery. Only 2 of 9 (22%) patients who underwent Dx/HA injection had resolution of their reflux. Of the remaining seven, five required open ureteral reimplantation (two for obstruction), one lost the graft due to rejection, and one had significant hydronephrosis. eGFR was similar between the hydronephrosis, UTI, and abnormal renal biopsy groups at all times.CONCLUSION: Patients with transplant VUR and recurrent febrile UTI are more likely to require surgical therapy, but the complication and failure rate for Dx/HA injection is significant. Patients with transplant VUR without febrile UTI can be successfully managed with bladder training and temporary antibiotic prophylaxis.

    View details for DOI 10.1111/petr.13299

    View details for PubMedID 30324753

  • Predictors of poor neonatal outcomes in prenatally diagnosed multicystic dysplastic kidney disease. Journal of perinatology : official journal of the California Perinatal Association Balasundaram, M., Chock, V. Y., Wu, H. Y., Blumenfeld, Y. J., Hintz, S. R. 2018


    OBJECTIVE: Multicystic dysplastic kidney (MCDK) is one of the most common anomalies detected by prenatal ultrasound. Our objective was to identify factors associated with severe adverse neonatal outcomes of prenatally diagnosed MCDK STUDY DESIGN: A retrospective review of prenatally diagnosed MCDK (1 January 2009 to 30 December 2014) from a single academic center was conducted. The primary outcome was death or need for dialysis among live-born infants. Associations between prenatal characteristics and outcome were analyzed by Fisher's exact test and Mann-Whitney test.RESULTS: A total of 53 cases of prenatally suspected MCDK were included, of which 46 cases were live-born and confirmed postnatally (38 survivors, 8 non-survivors). Prenatally diagnosed extrarenal anomalies, bilateral MCDK, contralateral renal anomalies, and anhydramnios were significantly associated with death or need for dialysis (all p<0.0001).CONCLUSIONS: Prenatally identified findings are associated with adverse neonatal outcome, and can guide counseling and management planning. In the absence of significant associated findings, prenatally diagnosed unilateral MCDK has a benign neonatal course.

    View details for PubMedID 29572458

  • Young rats exhibit an age- and sex-dependent bladder response to alpha-antagonists but not beta-agonists JOURNAL OF PEDIATRIC UROLOGY Chien, C., Wu, H. 2016; 12 (2)


    Previous studies have suggested that the onset of alpha- (α) and beta- (β) adrenergic receptor activity is delayed in young animals. The use of alpha1- (α1-) antagonists for dysfunctional voiding, and beta3- (β3-) agonists for overactive bladder in younger children may not be indicated if maturation is required before bladder and urethral adrenergic receptors are active.To determine the sex- and age-dependent responses of the bladder and external urethral sphincter (EUS) to α- and β-adrenergic agents in neonatal and young adult rats.A total of 72 naïve Sprague-Dawley rats (36 female, 36 male) and 15 bladder-reduced (BR) female Sprague-Dawley rats underwent cystometry and EUS electromyography at 3, 6, and 9 weeks of life. Following administration of WAY 100,635 (0.3 mg/kg, serotonergic receptor antagonist), the non-selective α-agonist phenylephrine (0.3 mg/kg), α-antagonist phentolamine (1-3 mg/kg), β-agonist isoprenaline (3 mg/kg) and β-antagonist propranolol (3 mg/kg) were delivered intravenously. The maximum intravesical pressure (IVP), pressure threshold (PT), intermicturition interval (IMI), contraction duration (CD), burst amplitude and burst frequency were compared after each drug.The α-antagonist phentolamine lowered the IVP in 9-week-old males without lowering the PT. In contrast, the β-agonist isoprenaline lowered the IVP in both males and females of all ages, also without affecting the PT. Isoprenaline was also effective at shortening the CD in females, suggesting more effective bladder emptying. The α-agonist phenylephrine increased the IVP in 3-week-old and 6-week-old females and 3-week-old males, but this effect was blocked by pretreatment with phentolamine. The β-antagonist propranolol increased the PT in both males and females, and shortened the IMI in females, which was consistent with retention. Phenylephrine increased the burst duration in 9-week-old naïve females, while isoprenaline increased the burst amplitude and duration in 9-week-old BR females.In the neonatal rat, both α- and β-adrenergic receptors actively regulate bladder function by 3 weeks of life, but the desired effect of decreasing IVP by α-antagonists was delayed until 9 weeks in male rats. In contrast, β-agonists were effective at decreasing IVP in both male and female rats of all ages, which suggests that they are better agents for enhancing bladder emptying in female and young male rats.

    View details for DOI 10.1016/j.jpurol.2015.11.005

    View details for Web of Science ID 000375146500008

    View details for PubMedID 26897326

  • 2 year outcome for 8 year old female managed with partial cystectomy for primary bladder clear cell carcinoma. Urology case reports Diaz, E. C., Velasquez, M. G., Kao, C., Wu, H. 2019; 26: 100948


    Bladder cancer is rare in the pediatric population, and clear cell carcinoma is extremely rare with one other pediatric case reported. Here we report the clinical outcome for a medically complicated pediatric patient with muscle invasive clear cell carcinoma treated with partial cystectomy without neoadjuvant or adjuvant therapy. Final pathology was stage T2bN0M0 with negative margins. At 2 years, there is no disease recurrence by cystoscopy, chest and abdominal imaging. Postoperative issues have been related to reduced bladder capacity and compliance and the patient is currently managed with continuous urinary diversion and will require future definitive lower tract reconstruction.

    View details for DOI 10.1016/j.eucr.2019.100948

    View details for PubMedID 31293899

  • Editorial Comment. The Journal of urology Wu, H. 2019; 201 (1): 180–81

    View details for PubMedID 30577410

  • Commentary on "Pediatric urology fall congress 2017" Journal of pediatric urology Cooper, C., Herndon, C. D., Wu, H. Y. 2018; 14 (4): 316
  • Commentary on 'Pediatric urology fall congress 2016'. Journal of pediatric urology Cooper, C. S., Herndon, C. D., Wu, H. Y. 2017; 13 (4): 340
  • Book review of 'Perspectives in Pediatric Pathology, Volume 30. Development and pathology of the pediatric testis'. Journal of pediatric urology Wu, H. Y. 2017; 13 (5): 531
  • Sex differences in neonatal and young adult rat lower urinary tract function caused by bladder reduction. Journal of pediatric urology Chien, C., Chang, H. H., Wu, H. 2015; 11 (4): 197 e1-7


    Pediatric urinary incontinence has been proposed as a cause for adult urinary incontinence, yet animal models mimic the findings of overactive bladder more closely than dysfunctional voiding. We used the bladder reduction (BR) model to study the effects of early external urethral sphincter (EUS) dysfunction on the maturation of lower urinary tract function in neonatal and young adult rats of both sexes.To determine long-term alterations in bladder and EUS function in young adult rats caused by neonatal BR.46 Sprague-Dawley rats underwent BR and 52 underwent sham surgery at 1 week of age. At 3, 6, and 9 weeks of life, cystometry was carried out, 8-OH-DPAT (serotonergic receptor agonist) and WAY 100,635 (serotonergic receptor antagonist) were administered intravenously. Pressure threshold (PT), volume threshold (VT), storage tonic AUC, contraction area under the curve (AUC), EUS burst amplitude and burst duration were measured at baseline and after administration of serotonergic agents.PT increased in 3-week BR females compared with shams (31.1 vs. 22.7 cm H2O, p < 0.01), in conjunction with less efficient EUS emptying, as burst amplitude was suppressed (BR 0.04 vs. sham 0.07 mV, p < 0.05). VT subsequently increased in 9-week BR females compared with shams (0.81 vs. 0.36 mL, p < 0.05). Although 3-week BR males also experienced suppressed burst amplitude (BR 0.17 vs. sham 0.28 mV, p < 0.05), they showed no difference in PT at 3 weeks or VT at 9 weeks compared with sham males. The burst amplitude returned to normal in 6- and 9-week BR animals of both sexes, confirming a spontaneous recovery of EUS function over time. The thresholds for voiding in male rats are not as sensitive to early changes in EUS function compared with female rats. The response to serotonergic agents was identical between BR and sham animals. In the female animals, 8-OH-DPAT increased storage tonic AUC and burst duration, whereas in male animals, 8-OH-DPAT increased contraction AUC, burst amplitude, and burst duration. WAY 100,635 reversed the enhancements of EUS function caused by 8-OH-DPAT.BR caused a temporary impairment of EUS emptying at 3 weeks of life, similar to dysfunctional voiding, while serotonergic agonists remained effective at enhancing EUS emptying in BR animals. Although EUS emptying spontaneously improved, the increase in VT in female young adult rats suggests that timely treatment of EUS dysfunction is required to decrease the risk of long-term bladder dysfunction.

    View details for DOI 10.1016/j.jpurol.2015.05.009

    View details for PubMedID 26076824

  • Commentary to 'Astrocyte elevated gene-1 overexpression in histologically favorable Wilms tumor is related to poor prognosis'. Journal of pediatric urology Wu, H. 2014; 10 (2): 323-324

    View details for DOI 10.1016/j.jpurol.2013.09.013

    View details for PubMedID 24206782

  • Can evidence-based medicine change toilet-training practice? Arab journal of urology Wu, H. 2013; 11 (1): 13-18


    To assess the evidence showing that a specific method of toilet training (TT) is more effective than others, as any method of TT recommended by a physician faces obstacles because parents rarely request advice on TT from physicians, and TT practices vary tremendously across cultures and socioeconomic levels.Reports on the natural course of urinary incontinence in children and different methods of TT, published in English between 1946 and 2012, were reviewed. Specifically investigated were historical recommendations on TT, the prevalence of urinary incontinence during childhood, the outcome of TT methods, and the effect of culture and socioeconomic status on the choice of TT method and timing.TT now occurs at later ages than it did previously. This progression reflects changing ideas about normal childhood physiology and psychology. The prevalence of urinary incontinence in European countries progressively decreased in children aged between 6-7 years and 16-17 years old. TT methods change with increasing socioeconomic levels to 'child-centred' techniques applied at older ages, but the prevalence of urinary incontinence after 'parent-centred' techniques of TT at younger ages has not been studied. There is currently no evidence that a specific timing or method of TT is more effective or prevents voiding dysfunction.Follow-up studies of urinary continence in children toilet trained at 6-12 months of age might provide evidence for whether a given method or timing of TT is beneficial to prevent voiding dysfunction. The recommendations of physicians might be more readily adopted if they fit culturally accepted ideas of good parenting techniques.

    View details for DOI 10.1016/j.aju.2012.11.001

    View details for PubMedID 26579239

    View details for PubMedCentralID PMC4442913

  • The surgical management of paediatric bladder and prostate rhabdomyosarcoma. Arab journal of urology Wu, H. 2013; 11 (1): 40-46


    The surgical management of paediatric bladder/prostate rhabdomyosarcoma (B/P RMS) continues to develop, with the goal of maximising organ preservation while achieving successful cancer control. The timing of radiotherapy and surgical excision to improve event-free survival (EFS) and overall survival (OS) remains controversial.Previous reports in English on B/P RMS over the past 15 years were identified and reviewed, focusing on studies comparing the effects of radiotherapy and surgery for local control, the effect of local control on OS, and improved means of diagnosing viable tumour after chemotherapy.The concept of lowering the 'cost of cure' drives current protocols. Bladder-sparing surgery is possible for 80% of patients after initial chemotherapy, with a mean 5-year OS of 85%. Overall, half of the patients are continent of urine, and adding radiotherapy might increase the risk of incontinence. Previous studies suggesting that early radiotherapy achieved better EFS than delayed radiotherapy did not control for stage and size of the tumour, which are the primary determinants of EFS. Improved local control does not automatically translate into improved OS.The current role for the surgical management in B/P RMS is to achieve local control of tumours that do not respond to chemotherapy and radiotherapy. An improved means of detecting viable tumour after initial chemotherapy would improve the ability to decide when local therapy is necessary. The continuing challenge for urologists managing these children is knowing when bladder-sparing surgery would be the best therapy.

    View details for DOI 10.1016/j.aju.2012.11.003

    View details for PubMedID 26579243

    View details for PubMedCentralID PMC4442956

  • Achieving urinary continence in children NATURE REVIEWS UROLOGY Wu, H. 2010; 7 (7): 371-377


    Achievement of urinary continence is an important developmental step that most children attain with the assistance of their parents and caregivers. Debate continues as to the best time to toilet train; in some Asian and African cultures children are trained as infants, while training at age 2-3 years is more typical in Western cultures. Infant voiding is not merely a spinal reflex, as the sensation of bladder filling is relayed to the brain. However, the ability of the brain to inhibit bladder contractions, and to achieve coordinated bladder contraction with sphincter relaxation, matures over time. While there is a concern that later toilet training may be responsible for an increase in urinary incontinence in children, no controlled studies on early versus late toilet training exist to evaluate this hypothesis. A number of medical conditions such as spina bifida, posterior urethral valves, cerebral palsy and autism can cause incontinence and difficulties in toilet training. The decision to start toilet training a child should take into account both the parents' expectation of how independent the child will be in terms of toileting, and the child's developmental readiness, so that a realistic time course for toilet training can be implemented.

    View details for DOI 10.1038/nrurol.2010.78

    View details for Web of Science ID 000279651300003

    View details for PubMedID 20531385

  • Differential Effect of L-Cysteine in Isolated Whole-Bladder Preparations from Neonatal and Adult Rats JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Buyuknacar, H. S., Gocmen, C., de Groat, W. C., Kumcu, E. K., Wu, H., Onder, S. 2010; 333 (1): 228-235


    The present study was undertaken to compare the effects of the thiol reagents L-cysteine and (diazene dicarboxylic acid bis 5N,N-dimethylamide) diamide on contractile activity of neonatal and adult rat bladders. In vitro whole-bladder preparations from Wistar rats were used to study the modulation of spontaneous bladder contractions by thiol reagents. After blocking cholinergic and adrenergic transmission with atropine and guanethidine, L-cysteine facilitated spontaneous bladder contractions in neonatal rat bladders. The effect of L-cysteine was suppressed by diamide. Diamide alone did not change basal activity of the neonatal rat bladder. The facilitatory effects of L-cysteine were reduced by the L-type Ca2+ channel-blocking agent nifedipine and the calcium-activated K+ channel opener NS1619 [1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one]. ATP or suramin, a purinergic receptor antagonist, significantly inhibited the effect of L-cysteine in neonatal bladders, whereas the nitric-oxide synthase inhibitor N(omega)-nitro-L-arginine was ineffective. L-cysteine did not elicit any detectable effects in the adult rat bladder; whereas diamide caused a large-amplitude sustained tonic contraction. The contraction induced by diamide in adult bladder did not occur when the preparation was pretreated with L-cysteine. Also, L-Cysteine administered during the diamide-evoked contraction completely inhibited the contraction to diamide. In conclusion, our results suggest that L-cysteine has markedly different effects in isolated whole-bladder preparations from neonatal and adult rats. Thus thiol-sensitive mechanisms may modulate contractility by regulation of Ca2+ and K+ channels and/or purinergic transmission in the neonatal bladder. The effects of L-cysteine and diamide were reversed in adult bladders, indicating that the regulation of bladder contractility by thiols is markedly altered during postnatal development.

    View details for DOI 10.1124/jpet.109.161661

    View details for Web of Science ID 000275793200024

    View details for PubMedID 20051484

  • Top-down Approach for Evaluation of Urinary Tract Infection UROLOGY Wu, H., Shortliffe, L. D. 2010; 75 (3): 514-515
  • Bladder Reduction Surgery Accelerates the Appearance of Spontaneous Voiding in Neonatal Rats JOURNAL OF UROLOGY Ng, Y., Wu, H., Lee, K. H., Yeung, C. K. 2010; 183 (1): 370-377


    Patients with nocturnal enuresis may have small functional bladder capacity or altered bladder fullness sensation. We determined whether reducing bladder volume would affect the central inhibition of voiding that is normally present between birth and 2 weeks of life in neonatal rats.One and 3-week-old Sprague-Dawley rats underwent 50% bladder volume reduction by suture closure of the bladder dome. T8-T10 spinal cord injury was done in select animals. Latency of the perigenital-bladder reflex, spontaneous voiding onset and body weight were measured. Cystometry using urethane anesthesia, and measurements of in vitro spontaneous and KCl evoked contractions were done.Bladder reduction surgery led to the immediate appearance of spontaneous voiding in 1-week-old rats. Cystometry at 2 weeks showed voiding contractions in rats with bladder reduction, which was abolished by acute T8-T10 spinalization. Voiding contractions were not seen in animals with sham surgery or concurrent T8-T10 spinalization and bladder reduction. The perigenital-bladder reflex, somatic growth, spontaneous bladder contractions and bladder contractility were not affected by bladder reduction. Bladder capacity at 9 weeks was significantly larger in animals that underwent bladder reduction at 1 week than in sham treated animals (540 vs 256 microl, p = 0.04) but not in animals that underwent bladder reduction at 3 weeks.Bladder reduction removes the central inhibition of spontaneous voiding in neonatal rats. This suggests that decreased neonatal bladder capacity may alter how the brain regulates the bladder.

    View details for DOI 10.1016/j.juro.2009.08.108

    View details for Web of Science ID 000272649300138

    View details for PubMedID 19914665

  • Genitourinary rhabdomyosarcoma: Which treatment, how much, and when? JOURNAL OF PEDIATRIC UROLOGY Wu, H., Snyder, H. M., Womer, R. B. 2009; 5 (6): 501-506


    To review the current management of pediatric genitourinary rhabdomyosarcoma (RMS).Studies performed by the Intergroup Rhabdomyosarcoma Study Group, Children's Oncology Group (COG), International Society of Paediatric Oncology (SIOP) and others over the past 10 years were reviewed to compare the use of surgery, chemotherapy, and radiotherapy for treatment of RMS and their associated outcomes.Equivalent overall survival rates were reported in the last COG and SIOP trials, with worse event-free survival rates for bladder/prostate RMS in SIOP trials. The use of radiotherapy for local control was the main difference between current COG and SIOP protocols. Surgery is used to diagnose RMS, and for local control after chemotherapy. Chemotherapy is used for systemic control of RMS, but metastatic RMS will require new approaches.Risk stratification and risk-based therapy are being studied to decrease morbidity from treatment of RMS. The proper role of surgery vs radiotherapy for local control and whether additional treatment with second-line chemotherapy outweighs the avoidance of radiotherapy remain to be defined.

    View details for DOI 10.1016/j.jpurol.2009.06.011

    View details for Web of Science ID 000208054400017

    View details for PubMedID 19640790

  • Quantitative Ultrasound Renal Parenchymal Area Correlates With Renal Volume and Identifies Reflux Nephropathy 60th Annual Meeting of the American-Academy-of-Pediatrics/International-Childrens-Continence-Society Wong, I. Y., Copp, H. L., Clark, C. J., Wu, H., Shortliffe, L. D. ELSEVIER SCIENCE INC. 2009: 1683–87


    Studies show that renal volume on magnetic resonance imaging correlates with differential function and is decreased in children with vesicoureteral reflux diagnosed after urinary tract infection. We examined the correlation between ultrasound renal parenchymal area and magnetic resonance imaging volume to determine whether quantitative ultrasound renal parenchymal area might be a reliable, less costly and less invasive substitute for renal magnetic resonance imaging volume.To determine the correlation of ultrasound renal parenchymal area with magnetic resonance imaging, we identified 82 children with primary vesicoureteral reflux who underwent renal magnetic resonance imaging and ultrasound. Magnetic resonance imaging volume was compared with ultrasound renal parenchymal area, renal length and calculated ellipsoid volume. To determine the correlation of ultrasound renal parenchymal area with reflux grade, ultrasound renal parenchymal area was examined in 96 children with reflux and urinary tract infection, and in 52 with reflux without urinary tract infection. Linear regression and multivariate analysis were performed to find the relationship between ultrasound renal parenchymal area and reflux grade.The correlation of ultrasound renal parenchymal area with magnetic resonance imaging volume was superior to that of renal length and calculated ellipsoid volume (r(2) = 0.90 vs 0.83 and 0.84, respectively). Hydronephrosis did not affect the correlation. On multiple regression analysis in children with reflux and urinary tract infection higher reflux grade correlated with decreased ultrasound renal parenchymal area (p = 0.0016). In children with reflux without urinary tract infection reflux grade did not correlate with decreased ultrasound renal parenchymal area (p = 0.47).Ultrasound renal parenchymal area correlates closely with magnetic resonance imaging derived 3-dimensional renal volume and is capable of detecting progressive renal area loss in patients with reflux and urinary tract infection. More studies are necessary to verify whether data from more invasive tests, such as renal magnetic resonance imaging and dimercapto-succinic acid scan, may be attained from ultrasound renal parenchymal area alone.

    View details for DOI 10.1016/j.juro.2009.03.075

    View details for Web of Science ID 000269764300009

    View details for PubMedID 19692072

  • Postnatal Development of Voiding Reflexes and Bladder Smooth Muscle Properties: An Overview of Recent Findings LUTS-LOWER URINARY TRACT SYMPTOMS Ng, Y., Wu, H. 2009; 1: S74-S76
  • Activation of the nitric oxide-cGMP pathway reduces phasic contractions in neonatal rat bladder strips via protein kinase G AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Artim, D. E., Kullmann, F. A., Daugherty, S. L., Wu, H., de Groat, W. C. 2009; 297 (2): F333-F340


    Nitric oxide (NO), a neurotransmitter in the lower urinary tract, stimulates soluble guanylyl cyclase (sGC) and in turn cGMP-dependent protein kinase G (PKG) to modulate a number of downstream targets. NO donors reduce bladder hyperactivity in some pathological models but do not affect normal bladder activity in the adult rat. In this study, the NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP; 100 microM) decreased the amplitude and frequency of spontaneous and carbachol-enhanced contractions in neonatal rat bladder strips, which are intrinsically hyperactive. This effect was blocked by inhibition of sGC and mimicked by application of a membrane-permeable cGMP analog (8-bromo-cGMP, 100 microM). Inhibition of PKG prevented or reversed the inhibitory effects of 8-bromo-cGMP. A portion of the SNAP-mediated inhibition was also dependent upon PKG; however, a short-lasting, sGC-dependent inhibitory effect of SNAP was still present after PKG inhibition. Inhibition of NO synthase with L-NAME (100 microM) did not change the amplitude or frequency of contractions. However, inhibition of endogenous phosphodiesterase (PDE)-5 with zaprinast (25 microM) reduced the amplitude and frequency of phasic contractions and increased the magnitude of inhibition produced by maximal concentrations of SNAP, suggesting that endogenous PDEs are constitutively active and regulate cGMP production. These results suggest that the NO-cGMP-PKG pathway may be involved in inhibitory control of the neonatal rat bladder.

    View details for DOI 10.1152/ajprenal.00207.2009

    View details for Web of Science ID 000268276300012

    View details for PubMedID 19493964

  • When is prior ureteral stent placement necessary to access the upper urinary tract in prepubertal children? JOURNAL OF UROLOGY Corcoran, A. T., Smaldone, M. C., Mally, D., Ost, M. C., Bellinger, M. F., Schneck, F. X., Docimo, S. G., Wu, H. 2008; 180 (4): 1861-1863


    We studied the possibility that age, height, weight and body mass index could be used to predict the likelihood of successful ureteroscopic access to the upper urinary tract without previous stent placement in prepubertal children.We retrospectively reviewed all ureteroscopic procedures for upper tract calculi in prepubertal children from 2003 to 2007. We compared age, height, weight and body mass index in patients who underwent successful primary flexible ureteroscopic access and in those who required initial stent placement to perform ureteroscopy.Successful primary ureteroscopic access to the upper tract was achieved in 18 of 30 patients (60%). There was no difference in mean age (9.9 vs 9.5 years, p = 0.8), height (132 vs 128 cm, p = 0.6), weight (37 vs 36 kg, p = 0.86) or body mass index (19.3 vs 20.5 kg/m(2), p = 0.55) between patients with successful vs unsuccessful upper tract access. Locations that prevented access to the upper urinary tract were evenly distributed among the ureteral orifice, iliac vessels and ureteropelvic junction.Age, height, weight and body mass index could not predict the likelihood of successful ureteroscopic access to the upper tract. Placement of a ureteral stent for passive ureteral dilation is not necessary for successful ureteroscopic access to the renal pelvis in prepubertal children. An initial attempt at ureteroscopy, with placement of a ureteral stent if upper tract access is unsuccessful, decreases the number of procedures while maintaining a low complication rate.

    View details for DOI 10.1016/j.juro.2008.03.106

    View details for Web of Science ID 000259382400135

    View details for PubMedID 18721946

  • Computerized tomography findings in pediatric renal trauma - Indications for early intervention? JOURNAL OF UROLOGY Cannon, G. M., Polsky, E. G., Smaldone, M. C., Gaines, B. A., Schneck, F. X., Bellinger, M. F., Docimo, S. G., Wu, H. 2008; 179 (4): 1529-1532


    We sought to determine if initial computerized tomography findings in pediatric patients suffering blunt renal trauma with urinary extravasation were predictive of the need for operative intervention.A total of 17 patients with grade IV blunt renal trauma and urinary extravasation were identified between 2000 and 2007. Each computerized tomogram was reviewed to determine location, size and number of sites of extravasation, as well as the presence of contrast material in the ipsilateral ureter. These findings were compared with subsequent ureteral stent placement, percutaneous urinoma drainage, angiographic embolization and nephrectomy.A total of 13 male and 4 female patients (mean age 11.1 years) were identified. Eight patients (47%) required delayed intervention. Conservative treatment was unsuccessful in patients with absence of contrast material in the ipsilateral ureter and large separation of the upper and lower poles, and in 3 of 5 patients with multiple areas of extravasation and 4 of 5 patients with transfusion requirements. The diameter (9.6 vs 9.7 mm, p = 0.96) and location of extravasation were not predictive of subsequent intervention. Two of 5 patients with posterior extravasation required intervention, both for symptomatic urinoma.Early ureteral stent placement may be considered for pediatric patients with blunt renal trauma who demonstrate absence of contrast material in the ipsilateral ureter, since clinical indications for stent placement will likely develop. Further study may show if wide separation of the upper and lower poles, multiple areas of extravasation and transfusion requirement are factors in the decision for early intervention.

    View details for DOI 10.1016/j.juro.2007.11.094

    View details for Web of Science ID 000254175000075

    View details for PubMedID 18295268

  • Commentary to 'Pediatric flexible ureteroscopic lithotripsy as first line approach'. Journal of urology Wu, H. Y. 2008; 180 (6): 2619
  • Is ureteroscopy first line treatment for pediatric stone disease? JOURNAL OF UROLOGY Smaldone, M. C., Cannon, G. M., Wu, H., Bassett, J., Polsky, E. G., Bellinger, M. F., Docimo, S. G., Schneck, F. X. 2007; 178 (5): 2128-2131


    We report our current outcomes for ureteroscopic management of pediatric stone disease.We carried out a retrospective review of all ureteroscopic procedures for kidney or ureteral calculi performed between 2001 and 2005. Stone location and size, preoperative and postoperative stenting, intraoperative dilation, use of ureteral access sheath, stone-free rates and complications were noted.A total of 100 patients (58% female, mean age 13.2 years) underwent 115 procedures. Stones were located in the renal pelvis in 6% of patients, upper pole in 10%, mid ureter in 11%, lower pole in 17%, proximal ureter in 19% and distal ureter in 37%. Mean stone size was 8.3 mm (median 7.0), with a mean of 1.5 stones per patient. Preoperative stenting was used in 54% of patients, and a stent was placed postoperatively in 76%. Ureteral coaxial dilators and ureteral access sheaths were used in 70% and 24% of patients, respectively. There were no major intraoperative complications, although 5 patients required stent placement for ureteral perforation or extravasation. One patient had a ureteral stricture requiring ureteral reimplantation. Mean followup was 10.1 months (median 2.6). Stone-free rate was 91% on followup ultrasound, abdominal radiography or computerized tomography. Seven patients required staged ureteroscopic procedures to achieve stone-free status. While the number of percutaneous nephrolithotomy and shock wave lithotripsy cases remained stable, the number of ureteroscopic cases increased 7-fold during this period.Improved ureteroscopic access to stones throughout the pediatric urinary tract and stone-free rates that are comparable to the adult population have led to the adoption of ureteroscopy as first line therapy in children at our institution.

    View details for DOI 10.1016/j.juro.2007.07.050

    View details for Web of Science ID 000250187000079

    View details for PubMedID 17870124

  • Ureteroscopic management of lower-pole stones in a pediatric population 24th World Congress of Endourology Cannon, G. M., Smaldone, M. C., Wu, H., Bassett, J. C., Bellinger, M. F., Docimo, S. G., Schneck, F. X. MARY ANN LIEBERT INC. 2007: 1179–82


    We report our experience with ureteroscopy to treat lower-pole calculi in children.A retrospective review was conducted of all ureteroscopic procedures for lower-pole stone disease at a pediatric institution from 2000 through 2005. A total of 13 girls and 8 boys with a mean age of 15 years (range 1-20 years) underwent flexible ureteroscopy for lower-pole calculi. The mean stone burden was 12 mm. Stone-free status was defined by postoperative abdominal radiography, CT, or ultrasonography.Ureteral stenting was performed preoperatively in 38% and postoperatively in 71% of the patients. Ureteral-access sheaths were placed in 43%. There were no intraoperative or postoperative complications. With a mean follow-up of 11 months, 76% of the children were stone-free. The success rate for stones <15 mm was 93% v 33% for stones > or =15 mm (P = 0.01).Ureteroscopy and laser lithotripsy are safe and effective in children with lower-pole calculi. Ureteroscopy can be considered a primary treatment option for children with lower-pole calculi <15 mm.

    View details for DOI 10.1089/end.2007.9911

    View details for Web of Science ID 000250735100012

    View details for PubMedID 17949321

  • Dirt bikes and all terrain vehicles: The real threat to pediatric kidneys 58th Annual Meeting of the American-Academy-of-Pediatrics Wu, H., Gaines, B. A. ELSEVIER SCIENCE INC. 2007: 1672–74


    Recent reviews show that bicycles are the major cause of significant renal injury with few injuries occurring during contact sports. All-terrain vehicles are also responsible for significant pediatric renal trauma. We determined whether dirt bikes and all-terrain vehicles cause more significant renal injuries than contact sports.A retrospective review of our pediatric trauma database revealed 115 consecutive patients treated for renal trauma from 2000 to 2005. A total of 20 bicycle injuries occurred, including 6 on dirt bikes. A total of 13 all-terrain vehicle injuries occurred, including 4 involving rollovers. A total of 12 contact sport injuries occurred, including 2 during pick-up games. The mean grade of renal injury was compared among the mechanisms, with grades III-V considered high grade.In descending order of renal injury the mechanisms were dirt bike (2.8), all-terrain vehicle rollover (2.8), bicycle (2.3), all-terrain vehicle (2.1), contact sports (1.8) and organized contact sports (1.4). Dirt bikes and all-terrain vehicle rollovers caused significantly greater renal trauma than organized contact sports (2.8 vs 1.4, p = 0.007 and 0.02, respectively), whereas overall bicycle and all-terrain vehicle accidents resulted in similar renal trauma grades compared to those of all contact sports. The 2 high grade renal injuries during contact sports occurred during pick-up football games without protective gear.Physician advice regarding children with a solitary kidney should include avoiding dirt bikes and all-terrain vehicles. Efforts to limit all-terrain vehicle use in children younger than 16 years would decrease the risk of significant renal injury in this population more effectively than limiting contact sports participation.

    View details for DOI 10.1016/j.juro.2007.03.160

    View details for Web of Science ID 000249568400037

    View details for PubMedID 17707026

  • Smooth muscle and neural mechanisms contributing to the downregulation of neonatal rat spontaneous bladder contractions during postnatal development AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY Ng, Y., de Groat, W. C., Wu, H. 2007; 292 (5): R2100-R2112


    Spontaneous bladder contractions (SBCs) in the neonatal rat urinary bladder change from a high-amplitude, low-frequency pattern to a low-amplitude, high-frequency pattern during the first 6 wk of life. Understanding the mechanism of this developmental change may provide insights into the causes of bladder overactivity in adults. In vitro whole bladder preparations from Sprague-Dawley rats were used to study the modulation of SBCs by calcium-activated potassium channels (K(Ca)) and electrical field stimulation from 3 days to 6 wk of life. SBCs in 3-day-old bladders were unmasked by treatment with iberiotoxin (100 nM), an inhibitor of large conductance K(Ca) (BK) channels, or apamin (100 nM), an inhibitor of small conductance K(Ca) (SK) channels. Iberiotoxin significantly increased the magnitude of SBCs at 2-3 wk, whereas apamin was only effective at 6 wk. In 1-2 wk bladders, exposure to room temperature Krebs solution decreased SBCs. This decrease was reversed by activating intramural nerves with electrical field stimulation. The effect of electrical field stimulation was inhibited by atropine (1 microM), suramin (10 microM), or pretreatment with tetrodotoxin (1 microM) but was not reversed by tetrodotoxin applied after electrical field stimulation. BK-alpha mRNA increased threefold, and BK-alpha protein increased fivefold from 3 days to 6 wk. These data suggest that BK channels play an important role in the regulation of SBCs in the neonatal bladder and that both increased BK channel activity, as well as changes in smooth muscle sensitivity to locally released neurotransmitters contribute to the downregulation of SBCs during early postnatal development.

    View details for DOI 10.1152/ajpregu.00779.2006

    View details for Web of Science ID 000247725200040

    View details for PubMedID 17234952

    View details for PubMedCentralID PMC3111975

  • Acute renal failure from xanthine nephropathy during management of acute leukemia PEDIATRIC NEPHROLOGY LaRosa, C., McMullen, L., Bakdash, S., Ellis, D., Krishnamurti, L., Wu, H., Moritz, M. L. 2007; 22 (1): 132-135


    Tumor lysis syndrome is a potentially life-threatening complication of induction chemotherapy for treatment of lymphoproliferative malignancies. Serious complications of tumor lysis syndrome are rare with the preemptive use of allopurinol, rasburicase, and urine alkalinization. We report a case of oliguric acute renal failure due to bilateral xanthine nephropathy in an 11-year-old girl as a complication of tumor lysis syndrome during the treatment of T-cell acute lymphoblastic leukemia. Xanthine nephrolithiasis results from the inhibition of uric acid synthesis via allopurinol which increases plasma and urinary xanthine and hypoxanthine levels. Reports of xanthine nephrolithiasis as a cause of tumor lysis syndrome are rare in the absence of defects in the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) enzyme. Xanthine nephropathy should be considered in patients who develop acute renal failure following aggressive chemotherapy with appropriate tumor lysis syndrome prophylaxis. Urine measurements for xanthine could aid in the diagnosis of patients with nephrolithiasis complicating tumor lysis syndrome. Allopurinal dosage should be reduced or discontinued if xanthine nephropathy is suspected.

    View details for DOI 10.1007/s00467-006-0287-z

    View details for Web of Science ID 000242513200023

    View details for PubMedID 17039332

  • Muscarinic regulation of neonatal rat bladder spontaneous contractions AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY Ng, Y., de Groat, W. C., Wu, H. 2006; 291 (4): R1049-R1059


    In vitro preparations of whole urinary bladders of neonatal rats exhibit prominent myogenic spontaneous contractions, the amplitude and frequency of which can be increased by muscarinic agonists. The muscarinic receptor subtype responsible for this facilitation was examined in the present experiments. Basal spontaneous contractions in bladders from 1- to 2-wk-old Sprague-Dawley rats were not affected by M2 or M3 receptor antagonists. However, administration of 0.5 microM physostigmine, an anticholinesterase agent that increases the levels of endogenous acetylcholine, or 50-100 nM carbachol, a cholinergic agonist at low concentrations, which did not cause tonic contractions, significantly augmented the frequency and amplitude of spontaneous contractions. Blockade of M2 receptors with 0.1 microM AF-DX 116 or 1 microM methoctramine or blockade of M3 receptors with 50 nM 4-diphenylacetoxy-N-methylpiperidine methiodide or 0.1 microM 4-diphenylacetoxy-N-(2-chloroethyl)piperidine hydrochloride (4-DAMP mustard) reversed the physostigmine and carbachol responses. M2 and M3 receptor blockade did not alter the facilitation of spontaneous contractions induced by 10 nM BAY K 8644, an L-type Ca2+ channel opener, or 0.1 microM iberiotoxin, a large-conductance Ca2+-activated K+ channel blocker. NS-1619 (30 microM), a large-conductance Ca2+-activated K+ channel opener, decreased carbachol-augmented spontaneous contractions. These results suggest that spontaneous contractions in the neonatal rat bladder are enhanced by activation of M2 and M3 receptors by endogenous acetylcholine released in the presence of an anticholinesterase agent or a cholinergic receptor agonist.

    View details for DOI 10.1152/ajpregu.00236.2006

    View details for Web of Science ID 000240457600023

    View details for PubMedID 16709645

  • Dysfunctional elimination syndrome is a negative predictor for vesicoureteral reflux. Journal of pediatric urology Colen, J., Docimo, S. G., Stanitski, K., Sweeney, D. D., Wise, B., Brandt, P., Wu, H. 2006; 2 (4): 312-315


    We investigated the likelihood of finding vesicoureteral reflux (VUR) in patients with urinary tract infections (UTIs), accompanied by fever or dysfunctional elimination syndrome (DES).Two hundred consecutive voiding cystourethrograms performed in 1997-2002 for a diagnosis of UTI were reviewed. Fever, DES, and the grade and laterality of VUR were recorded. Patients were stratified into two groups by age to allow for assessment of DES symptoms in the older patient population: <2 years (n=68) and > or =2 years (n=132). Ratios were compared using a two-tailed Fisher's exact test.Of the children> or =2 years old, 64/132 (48%) had VUR. Patients who were non-febrile with DES were less likely than patients who were febrile without DES to have VUR [12/34 (35%) vs 23/34 (68%), P=0.02], whereas the risk of dilating VUR [5/34 (15%) vs 11/34 (32%), P=0.15] and bilateral VUR [4/34 (12%) vs 11/34 (32%), P=0.08] was not statistically different. In febrile patients, the presence of DES was associated with a lower risk of VUR [22/51 (43%) vs 23/34 (68%), P=0.03] and dilating VUR [5/51 (10%) vs 11/34 (32%), P=0.01], but not bilateral VUR [8/51 (16%) vs 11/34 (32%), P=0.11].Children with non-febrile UTI and DES have a significantly lower risk of having VUR compared to children with febrile UTI and no DES. Among children with a history of UTI, DES is a negative predictor for VUR.

    View details for DOI 10.1016/j.jpurol.2006.01.013

    View details for PubMedID 18947628

  • Maternal separation uncouples reflex from spontaneous voiding in rat pups JOURNAL OF UROLOGY Wu, H. Y., de Groat, W. C. 2006; 175 (3): 1148-1151


    Rat pups only void when the perigenital-bladder reflex is activated by the mother rat licking the perineum. Maternal separation causes bladder distention as well as stress responses and anxiety behaviors in adult rats. We determined if MS would change voiding reflex maturation in neonatal rats.A total of 14 Sprague-Dawley rat pups were subjected to 6 hours of daily MS and 17 were subjected to 6 hours of MS with bladder emptying by perigenital stimulation at 3 hours on postnatal days 2 to 14. Age matched controls for the 2 groups remained with the mother. Spontaneous voiding in awake pups from 1 to 3 weeks was monitored in a metabolic cage and perigenital-bladder reflex latency was determined from 1 to 7 weeks. Cystometry was performed at 9 weeks with the rats under urethane anesthesia.Spontaneous voiding began at 3 weeks in all animals. The latency of the perigenital-bladder reflex at 3 weeks was shorter than the latency at 2 days in MS animals (3.3 vs 6.4 seconds, p < 0.01) but not in control or MSPG animals. MS animals maintained the perigenital-bladder reflex 2 weeks longer than control animals. The spontaneous voiding behavior of MSPG animals was similar to that in controls.Intermittent bladder distention delays withdrawal of the spinal perigenital-bladder reflex but it does not affect maturation of the supraspinal bladder-bladder reflex that controls spontaneous voiding in older rats. This suggests that increased bladder afferent firing can selectively modulate spinal but not supraspinal mechanisms controlling postnatal changes in voiding function.

    View details for DOI 10.1016/S0022-5347(05)00321-6

    View details for Web of Science ID 000235289400091

    View details for PubMedID 16469642

  • Urinary ascites without hydronephrosis in a neonate with urethral atresia. Urology Stein, R. J., Noh, P. H., Wu, H. 2005; 66 (2): 432-?


    Urethral atresia is a rare and usually fatal cause of prenatal bladder outlet obstruction. We present a case of urethral atresia with urinary ascites to highlight the difficulties in making the diagnosis in the absence of hydronephrosis. We also discuss possible reasons why this patient maintained normal renal and pulmonary function.

    View details for PubMedID 16051320

  • Wilms' tumor management CURRENT OPINION IN UROLOGY Wu, H. Y., Snyder, H. M., D'Angio, G. J. 2005; 15 (4): 273-276


    The management of Wilms' tumor continues to evolve with two different approaches being taken by the National Wilms Tumor Study in North America and the International Society of Pediatric Oncology in Europe in regards to preoperative chemotherapy. Limiting the duration, dosage, and number of chemotherapeutic agents and the dosage of radiotherapy are common goals in both trials.Contralateral exploration of unilateral tumors will no longer be recommended in future National Wilms Tumor Studies. Percutaneous biopsy for tissue diagnosis is quite accurate, but there are concerning complications with its use. Partial nephrectomy is successful for low risk unilateral Wilms tumor, but its indications remain controversial. The surgical complication rate was similar between the National Wilms Tumor Study and the International Society of Pediatric Oncology, but intraoperative tumor spill was higher in the North American trials. Doxorubicin decreased the risk of recurrence in stage III tumors by 50%, and its current dose is not associated with late congestive heart failure. For selected patients, shorter courses of vincristine/dactinomycin or vincristine alone show equivalent results compared to current regimens. A longer course of chemotherapy (including doxorubicin) for clear cell sarcoma improves recurrence-free survival. Patients with Wilms' tumor, aniridia, major genitourinary malformations, and mental retardation, the WAGR syndrome, have a 50% chance of unexplained end-stage renal disease 20 years after treatment.Less aggressive means of diagnosis and treatment for Wilms' tumor are continuing to achieve very good cure rates while lowering long term morbidity for low risk patients. High-risk patients with unfavorable histology or the WAGR syndrome benefit from more intensive treatment and long-term follow-up.

    View details for Web of Science ID 000230074000014

    View details for PubMedID 15928519

  • Commentary to 'Dysfunctional elimination symptoms in childhood and adulthood'. Journal of urology Wu, H. Y. 2005; 174 (4): 1628
  • Pediatric urologic oncology: bladder, prostate, testis UROLOGIC CLINICS OF NORTH AMERICA Wu, H. Y., Snyder, H. M. 2004; 31 (3): 619-?


    Although treatment for bladder, prostate, and testis cancer comprises a large part of adult urologic practice, the tumors that affect these organs in children are rare. Rhabdomyosarcoma,which affects the bladder, prostate, vaginal, and paratesticular areas,is treated with a combination of surgery, chemotherapy, and radiation. Most transitional cell carcinomas of the bladder and prepubertal testis tumors are managed surgically owing to the low stage at presentation. Application of the technical advances learned in adults with tumors of the bladder, prostate, and testis, combined with an understanding of the difference in tumor biology, helps urologists improve the treatment of these tumors in children.

    View details for DOI 10.1016/j.ucl.2004.04.004

    View details for Web of Science ID 000223767000023

    View details for PubMedID 15313070

  • Surgical management of children with urolithiasis UROLOGIC CLINICS OF NORTH AMERICA Wu, H. Y., Docimo, S. G. 2004; 31 (3): 589-?


    The management of urolithiasis in children poses specific technical challenges that require planning before endoscopy and that affect the risks and outcomes of these procedures. The indications for operative intervention in children and adults are similar:infection, persistent symptoms of flank pain, nausea, and vomiting, as well as the failure to pass a ureteral stone after an appropriate trial of observation (3-6 weeks). Specific adjustments for performing extracorporeal shock wave lithotripsy, ureteroscopy, percutaneous nephrolithotomy, and cystolithotomy in children are discussed.

    View details for DOI 10.1016/j.ucl.2004.04.002

    View details for Web of Science ID 000223767000020

    View details for PubMedID 15313067

  • Decrease in maximal force generation in the neonatal mouse bladder corresponds to shift in myosin heavy chain isoform composition JOURNAL OF UROLOGY Wu, H. Y., Zderic, S. A., WEIN, A. J., Chacko, S. 2004; 171 (2): 841-844


    A change in calcium handling has been proposed as the cause of decreased maximal force generation by neonatal bladders with growth. Recent studies suggest that increased myosin heavy chain isoform SM1 increases force generation. We studied force generation in neonatal mouse bladders to determine if decreases in SM1 corresponded with decreased force.C57Bl/6 mice were studied from birth to 12 weeks of life (adulthood). The bladder strip contractile response to KCl and bethanechol was followed by the inhibition of rho-kinase activity by Y-27632. The mRNA levels for SM1/SM2 were determined using reverse transcriptase-polymerase chain reaction and protein levels were determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Muscle fraction per cross-sectional area was determined by trichrome staining.Newborn bladders generated significantly more tension in response to KCl (43.3 vs 17.4 mN/mm2, p = 0.02) and bethanechol (40.6 vs 11.9 mN/mm2, p = 0.05) than adult bladders. Inhibition of rho-kinase resulted in similar decreases in tension in all bladders. SM1 mRNA decreased slightly from 60% at birth to 50% at 12 weeks. SM1 protein decreased from 72.5% at birth to 50% by 3 weeks and it remained stable at 12 weeks. Total myosin per gm protein remained stable. Muscle fraction decreased from 63.8% at birth to 58.6% at 12 weeks (p = 0.4).We noted a decrease in SM1 that corresponded to a decrease in bladder force generation. The concept that SM1 contributes to the optimal assembly of myosin filaments suggests that changes in myosin isoforms may have a role in the decrease in voiding pressures seen in normal children.

    View details for DOI 10.1097/01.ju.000092554.83715.8f

    View details for Web of Science ID 000188319300095

    View details for PubMedID 14713839

  • Testis histopathology in boys with cryptorchidism correlates with future fertility potential JOURNAL OF UROLOGY Rusnack, S. L., Wu, H. Y., Huff, D. S., Snyder, H. M., Carr, M. C., Bellah, R. D., Zderic, S. A., Canning, D. A. 2003; 169 (2): 659-662


    We studied the ability of testis biopsy to predict eventual fertility potential.A total of 25 patients with unilateral undescended testis and 11 with bilateral undescended testes who previously underwent orchiopexy at a median age of 9 years were followed until after age 18 years. Semen analysis, testicular volume, follicle-stimulating hormone, luteinizing hormone, testosterone and inhibin B were compared to previously obtained biopsies of each testis. Biopsies were graded as mild, moderate or severe histology based on published data for normal and undescended testis histology.Patients with unilateral undescended testis and moderate histology were more likely to have a sperm density of greater than 20 million per cc than those with severe histology (p = 0.006), although no difference in hormonal parameters was noted. Patients with bilateral undescended testes and moderate histology were more likely to have normal follicle-stimulating hormone and inhibin B than those with severe histology (p = 0.05 and 0.002, respectively), although no difference in semen analysis was observed. Overall 7 of the 9 patients with bilateral undescended testes had less than 20 million sperm per cc.Testis biopsy provides useful prognostic information about semen analysis in patients with unilateral undescended testis. In the 9 patients with bilateral undescended testes testis biopsy divided them into normal and abnormal groups in terms of hormonal parameters. Testis biopsy was not able to provide additional prognostic information on semen analysis in patients with bilateral undescended testes since they were uniformly poor.

    View details for DOI 10.1097/01.ju.0000045701.25854.f3

    View details for Web of Science ID 000180458500063

    View details for PubMedID 12544338

  • Spontaneous regression of cystic dysplasia of the testis JOURNAL OF UROLOGY Thomas, A. D., Wu, H. Y., Canning, D. A., Snyder, H. M. 2003; 169 (2): 645-645
  • Genitourinary malformations in chromosome 22q11.2 deletion JOURNAL OF UROLOGY Wu, H. Y., Rusnack, S. L., Bellah, R. D., Plachter, N., McDonald-McGinn, D. M., Zackai, E. H., Canning, D. A. 2002; 168 (6): 2564-2565


    We reviewed our experience with genitourinary malformations associated with chromosome 22q11.2 deletion.We retrospectively reviewed patient intake charts at the 22q clinic at our institution. We assessed 73 renal/bladder ultrasounds and 7 autopsies performed between 1998 and 2000 for renal and bladder malformations. A total of 149 male patients were evaluated for possible testicular and urethral malformations.Of 80 patients 25 (31%) had a structural urinary tract anomaly. Another 8 patients had renal agenesis or multicystic dysplastic kidney, 4 had hydronephrosis and 5 had vesicoureteral reflux or an irregular bladder, while 8 of 73 (11%) had dysfunctional voiding, 9 of 149 (6%) had undescended testes and 12 of 149 (8%) had hypospadias.Screening renal/bladder ultrasound, careful voiding history and medical but not surgical therapy are recommended for renal and bladder anomalies associated with 22q11.2 deletion. The need for surgery for cryptorchidism and hypospadias is slightly higher than in the general population.

    View details for DOI 10.1097/01.ju.0000032176.07703.23

    View details for Web of Science ID 000179399900080

    View details for PubMedID 12441983

  • Spontaneous resolution of vesicoureteral reflux: A 15-year perspective JOURNAL OF UROLOGY Schwab, C. W., Wu, H. Y., Selman, H., Smith, G. H., Snyder, H. M., Canning, D. A. 2002; 168 (6): 2594-2599


    The spontaneous resolution rate of vesicoureteral reflux is helpful for determining the need for surgical intervention and the proper followup schedule in patients on antibiotic prophylaxis. We determined the resolution rate by patient rather than by ureter and analyzed the effects of laterality, gender, age and dysfunctional voiding.We retrospectively reviewed the records of 179 girls and 35 boys who presented between 1981 and 1984 with urinary tract infection and were diagnosed with primary vesicoureteral reflux. Mean age at presentation was 4.2 years and median followup was 3 years. Of the patients 107 (50%) had bilateral reflux and 60 had dysfunctional voiding. In 146 children (68%) reflux spontaneously resolved during the study. Patients were categorized by the worst grade of reflux, maintained on antibiotic prophylaxis and underwent voiding cystourethrography yearly until reflux resolved. Kaplan-Meier curves were constructed to define the resolution rate.Grades I to III reflux resolved at 13% yearly during the initial 5 years of followup and then at 3.5% yearly during subsequent followup. Grade IV to V reflux resolved at 5% rate yearly. Bilateral reflux resolved more slowly than unilateral reflux and it resolved more rapidly in boys than in girls. Untreated dysfunctional voiding had no effect on overall resolution.Grades I to III primary vesicoureteral reflux diagnosed after urinary tract infection resolve at identical rates and significantly more rapidly than grades IV to V. Early repair of grade IV to V reflux should be considered after age 18 months.

    View details for Web of Science ID 000179399900092

    View details for PubMedID 12441993

  • The ascending testis and the testis undescended since birth share the same histopathology JOURNAL OF UROLOGY Rusnack, S. L., Wu, H. Y., Huff, D. S., Snyder, H. M., Zderic, S. A., Carr, M. C., Canning, D. A. 2002; 168 (6): 2590-2591


    The etiology of the ascending testis is controversial. We propose that ascending testis, defined as a testis previously thought to be descended and later noted to be out of the scrotum, is due to mild hypogonadotropic hypogonadism affecting both testes. The diagnosis of these low types of true undescended testes is difficult to make clinically in children since they are frequently confused with retractile testes. In this study we compared testicular biopsies in a group of boys with ascending testes with those in boys who had an undescended testis since birth (primary undescended testis).Between 1985 and 1995, 91 patients with ascending testes underwent orchiopexy and bilateral testis biopsy. The total germ cell count, processus vaginalis status, age at surgery and whether followup was done by a pediatrician or pediatric urologist were compared in patients with ascending and unilateral primary undescended testes.The total germ cell count was similar in the undescended and the contralateral descended testis in patients with ascending and primary undescended testes. The processus vaginalis was more likely to be closed in ascending testes (57% versus 36%, p = 0.0001). Age at surgery and the total germ cell count were similar in patients followed by pediatricians and pediatric urologists.The ascending testis has the same germ cell count as the primary undescended testis. Yearly followup by the primary care physician is recommended for patients with retractile testes.

    View details for DOI 10.1097/01.ju.0000034026.01341.2a

    View details for Web of Science ID 000179399900090

    View details for PubMedID 12441991

  • Buccal mucosal grafts: Lessons learned from an 8-year experience Joint Meeting of the Pediatric-Academic-Societies/American-Academy-of-Pediatrics Metro, M. J., Wu, H. Y., Snyder, H. M., Zderic, S. A., Canning, D. A. ELSEVIER SCIENCE INC. 2001: 1459–61


    We evaluated our 8-year experience with buccal mucosal grafts in complex hypospadias and epispadias repair.We reviewed the records of 29 patients in whom a total of 30 buccal mucosal grafts were placed as part of urethral reconstruction between 1991 and 1999. At surgery 16 tubes and 14 onlays were constructed and 24 of 30 repairs involved the meatus. All patients were followed at least 6 months postoperatively (median 5.3 years). Beginning in 1995 meatal design was enlarged to a racquet handle shape and patients were asked to perform meatal self-dilation for 6 months postoperatively.Complications developed in 17 of our 30 cases (57%) and reoperation was done in 10 (33%). All complications were evident by 11 months postoperatively except 1 that presented as recurrent stricture disease at 3 years. Complications developed in 5 and 12 of 15 patients who underwent surgery between 1995 and 1999, and before 1995, respectively (p = 0.027). No patient has had meatal stenosis since 1995. Complications included meatal stenosis in 5 cases, stricture in 7, glanuloplasty, meatal and complete graft breakdown in 1 each, and fistula in 2. Onlays were more likely to result in stricture than tube grafts (6 of 14 cases versus 1 of 16, p = 0.034).The complication and reoperation rates of buccal mucosal grafts are 57% and 33% at 5 years of followup. Changes in meatal design and temporary postoperative meatal dilation have improved the outcome in the last 5 years. Buccal mucosa remains a good choice in patients who require extragenital skin for urethral reconstruction.

    View details for Web of Science ID 000170950100081

    View details for PubMedID 11547112

  • The histopathology of iatrogenic cryptorchid testis: An insight into etiology 95th Annual Meeting of the American-Urological-Association Fenig, D. M., Snyder, H. M., Wu, H. Y., Canning, D. A., Huff, D. S. ELSEVIER SCIENCE INC. 2001: 1258–61


    Iatrogenic undescended testis may develop after inguinal hernia repair, presumably as a result of mechanical tethering of the testis or cord in scar tissue. Because some true cryptorchid testes appear to be completely descended at birth and later ascend during childhood, some iatrogenic undescended testes may be low lying undescended testes. To determine whether iatrogenic undescended testes may be unrecognized cryptorchid testes at herniorrhaphy we examined biopsies of iatrogenic undescended testes and the corresponding contralateral descended testis.Between 1985 and 1999 bilateral testis biopsies were obtained at orchiopexy in 37 boys 1.5 to 11.8 years old who previously underwent inguinal hernia correction. Histomorphometric analysis of germ cell counts was performed on the undescended and contralateral descended testes, and compared to the count in bilateral biopsies of 37 age and position matched patients with true unilateral cryptorchidism.There were no significant differences in volume or total and differential germ cell counts in the undescended and contralateral descended testes in the study groups and age matched controls with primary unilateral cryptorchidism. The mean number of germ cells per tubule in the undescended testis in patients with a greater than 5-year interval from herniorrhaphy to orchiopexy was significantly decreased compared to those with an operative interval of less than 5 years (0.27 +/- 0.33 versus 0.93 +/- 1.4, p = 0.026).Some patients with iatrogenic undescended testis may have an unrecognized low cryptorchid testis. Careful physical examination before and after inguinal surgery is recommended. The early repair of iatrogenic undescended testis is warranted to prevent further damage.

    View details for Web of Science ID 000167503700083

    View details for PubMedID 11257697

  • High urinary flow accelerates renal injury in young rats with partial unilateral ureteral obstruction JOURNAL OF UROLOGY Nguyen, H. T., Wu, H. Y., Baskin, L. S., Kogan, B. A. 2000; 163 (6): 1904-1907


    We studied the effect of dietary manipulation and high urine flow on neonatal partial ureteral obstruction in a weanling rat preparation.A total of 40, 3-week old Sprague-Dawley rats underwent unilateral ureteral obstruction by burial of the right ureter in the psoas muscle and 13 underwent sham operation. Low, high and normal salt, and high sucrose diets were administered for 2 months. The glomerular filtration rate of each kidney was measured by iothalamate clearance. Intrapelvic pressure and renal blood flow were measured before and after acute volume loading.Fluid intake and urine output were 8 to 10-fold greater in animals on high salt and high sucrose diets compared to those in rats on normal and low salt diets. Hydronephrosis was observed only in rats with partial obstruction and high urine flow. No difference in renal weight was noted. Relative glomerular filtration rate of the partially obstructed kidney was maintained when urine flow was normal but decreased significantly with high urine flow. Total glomerular filtration rate also decreased with high urine flow. Intrapelvic pressure was elevated significantly at baseline in partially obstructed kidneys with high urine flow. All kidneys with partial obstruction had significantly increased intrapelvic pressure with volume loading. Renal blood flow was not significantly decreased in rats with high urine flow.Chronic high urine flow causes loss of renal function in partially obstructed weanling rat kidneys. Research should be done to determine whether human infants with hydronephrosis and partial ureteral obstruction would benefit from the prevention of increased fluid and salt intake.

    View details for Web of Science ID 000086984900115

    View details for PubMedID 10799225

  • Understanding bladder regeneration: Smooth muscle ontogeny Annual Meeting of the Section on Urology, of the American-Academy-of-Pediatrics Wu, H. Y., Baskin, L. S., Liu, W. H., Li, Y. W., Hayward, S. ELSEVIER SCIENCE INC. 1999: 1101–5


    We determined the origin of smooth muscle cells in acellular bladder matrix grafts.A total of 15 female Sprague-Dawley rats underwent partial cystectomy and grafting with an acellular matrix derived from rat bladder. The grafts were examined 1, 2, 3 and 4 weeks after grafting by immunohistochemical studies for smooth muscle markers and by transmission electron microscopy for smooth muscle morphology. Bladder matrix and bladder epithelium recombinants were created and grafted subcutaneously and under the renal capsule in nude mice. Recombinants were examined 1, 2, 3 and 4 weeks postoperatively by immunohistochemical studies for bladder epithelium and bladder smooth muscle.Smooth muscle ingrowth into acellular matrix was initially seen at 2 weeks. The immunohistochemical and electron microscopic characteristics of the cells were similar to those of fetal smooth muscle 2 weeks and newborn smooth muscle 4 weeks after grafting. Matrix epithelium recombinants displayed mature bladder epithelium with 3 to 7 layers but they did not support the ingrowth of smooth muscle cells.Mature bladder smooth muscle cells undergo dedifferentiation, migration and redifferentiation to repopulate an acellular matrix graft. It is unlikely that adult fibroblasts from the surrounding tissue are induced by epithelium and matrix to form smooth muscle. The contractile behavior of bladder substitute materials likely reflects the properties of the host bladder.

    View details for Web of Science ID 000081967100044

    View details for PubMedID 10458440

  • Ultrastructural smooth muscle ontogeny of the rat bladder International Bladder Research Congress Wu, H. Y., Baskin, L. S., Blakey, C., Goodman, J., Cunha, G. R. KLUWER ACADEMIC/PLENUM PUBL. 1999: 93–102


    The transmission electron microscope characteristics of developing rat bladder smooth muscle are described at 14 and 18 days of gestation, birth, and adulthood. Caveolae, microfilaments, and dense bodies increase during smooth muscle development. Collagen content in the extracellular matrix also increases. These changes may reflect increased bladder emptying in the rat, and also allow for comparison of smooth muscle cells in studies of bladder wound healing and tissue substitutes.

    View details for Web of Science ID 000081630200009

    View details for PubMedID 10599416

  • Long-term benefits of early neurosurgery for lipomyelomeningocele JOURNAL OF UROLOGY Wu, H. Y., Kogan, B. A., Baskin, L. S., Edwards, M. S. 1998; 160 (2): 511-514


    Our previous experience with early neurosurgery for lipomyelomeningocele revealed that patients undergoing repair before age 1.5 years were more likely to have normal bladder function. We evaluate the durability of the urological benefits in patients with lipomyelomeningocele with longer followup.A retrospective chart review was performed on all patients who underwent urodynamic testing before and after primary neurosurgical repair of lipomyelomeningocele. A total of 43 patients presented between 1983 and 1995 with at least 12 months of followup (median 68, range 15 to 167).Of the 43 patients 36 (84%) maintained stable clinical and urodynamic function, and 7 (16%) had late deterioration, which occurred between 9 months and 8 years postoperatively. Of 19 patients with normal urodynamic studies preoperatively 14 (74%) maintained normal function. Overall, 14 of 43 patients (33%) with lipomyelomeningocele had normal bladder and sphincter function during followup. The principal predictor of long-term normal bladder function was preoperative urodynamic status, since urodynamic studies were preoperatively normal in 13 of 14 patients (93%) who maintained normal bladder and sphincter function. Late neurosurgery was equally efficacious if urodynamic studies were normal.Our data continue to support early diagnosis and neurosurgical intervention in patients with lipomyelomeningocele, since there is a higher likelihood of normal preoperative function that can be preserved. Furthermore, the results are durable in 84% of cases. However, close followup is necessary, since deterioration can occur up to 8 years postoperatively.

    View details for Web of Science ID 000074928200075

    View details for PubMedID 9679919

  • Neurogenic bladder dysfunction due to myelomeningocele: Neonatal versus childhood treatment JOURNAL OF UROLOGY Wu, H. Y., Baskin, L. S., Kogan, B. A. 1997; 157 (6): 2295-2297


    We sought to determine whether the neonatal institution of treatment of neurogenic bladder dysfunction in myelomeningocele patients at high risk for urinary tract deterioration improves renal and bladder outcome.We reviewed the records of patients with bladder dysfunction believed to be at high risk for renal deterioration based on urodynamic studies. All patients were treated with clean intermittent catheterization. We compared rates of urinary infection, hydronephrosis, reflux, continence and surgical intervention in 46 patients in whom treatment was started in year 1 of life and 52 treated after age 4 years.Renal outcome was similar in both groups with persistent hydronephrosis in 6 of 46 patients (13%) and 7 of 52 (14%), respectively. However, significantly fewer bladder augmentation procedures were required in patients started on treatment during year 1 of life (5 of 46, 11% versus 14 of 52, 27%, p < 0.05).In addition to any psychological benefit, early intervention with clean intermittent catheterization in children with neurogenic bladder dysfunction may help to prevent irreversible bladder dysfunction and limit the need for bladder augmentation.

    View details for Web of Science ID A1997WY05000099

    View details for PubMedID 9146656

  • Effects of purines on rabbit corpus cavernosum contractile activity. International journal of impotence research Wu, H. Y., Broderick, G. A., Suh, J. K., Hypolite, J. A., LEVIN, R. M. 1993; 5 (3): 161-167


    At least three well documented neuropharmacologic mediators participate in physiologic erection: inhibition or cessation of alpha-adrenergic transmission, increases in both cholinergic (acetylcholine) and non-adrenergic non-cholinergic (NANC) transmission. In-vitro studies of rabbit corporal smooth muscle reveal that adenosine tri-phosphate (ATP) has a variable effect on muscle tension depending on the level of basal tone. ATP has a pronounced relaxant effect on corporal smooth muscle at either high basal tension or pre-stimulated tension. ATP stimulates a contraction in corporal smooth muscle at low tension. The current studies compare the effects of a series of purines (adenine, adenosine, AMP, ADP, ATP and beta-gamma methylene ATP) on both basal tension and on field-stimulated relaxation. The results demonstrate that all purines relax both baseline tension (2g) and phenylephrine-stimulated contraction. Following phenylephrine pre-stimulation: beta-gamma methylene ATP was significantly more potent than ATP at inhibiting tension. ADP, AMP, adenosine, and adenine produced intermediate dose-response relaxation curves. At 2 grams baseline tension, adenosine, ADP, and AMP were equally potent relaxing agents, ATP was slightly less potent. Adenine and beta-gamma-methylene ATP induced similar dose-response curves which were significantly less potent and efficacious than adenosine, AMP, ADP, and ATP. Field stimulation of phenylephrine pre-contracted tissue strips produce relaxation at both low and high frequencies. None of the purines either facilitated or inhibited the corporal response to field stimulation. We conclude that field stimulated relaxation of rabbit corporal smooth muscle is independent of purinergic relaxation.

    View details for PubMedID 8124434



    There are 2 competing theories regarding the pathogenesis of testicular agenesis--the endocrinopathy/cryptorchidism and the mechanical/intrauterine torsion theories. We compare the number of Leydig cells, total number of germ cells and the transformation of adult dark spermatogonia into primary spermatocytes in semithin sections of testicular biopsies from 59 contralateral descended testes of patients with testicular agenesis with those in the contralateral descended testes from 250 patients with unilateral cryptorchidism. The contralateral descended testes from boys with testicular agenesis demonstrated higher numbers of Leydig cells, higher numbers of total germ cells and a higher rate of transformation of adult dark spermatogonia into primary spermatocytes than did the contralateral descended testes from the patients with unilateral cryptorchidism. These findings favor the mechanical/intrauterine torsion theory over the endocrinopathy/cryptorchidism theory in the pathogenesis of testicular agenesis.

    View details for Web of Science ID A1991FZ77600032

    View details for PubMedID 1677689