Accuracy of point-of-care ultrasound by pediatric emergency physicians for testicular torsion.

INTRODUCTION: Acute scrotum is a common presentation to the pediatric emergency department, and ultrasound is frequently used to narrow the differential diagnosis. Point-of-care ultrasound (POCUS) is increasingly used by urologists and emergency physicians and could potentially be used to detect pediatric testicular torsion. OBJECTIVES: This study aimed to determine the accuracy of POCUS by pediatric emergency physicians in diagnosing testicular torsion and the agreement between point-of-care ultrasound and final diagnosis for other causes of acute scrotum. STUDY DESIGN: A chart review of patients presenting to the study emergency department who received POCUS by a pediatric emergency physician, as well as radiology department ultrasound and/or surgery, was performed. Charts were reviewed for POCUS diagnoses, final diagnoses, and imaging time metrics. RESULTS: A total of 120 patients met study criteria, with 12 cases of testicular torsion. The diagnostic accuracy of POCUS for testicular torsion is described in the summary table. For all causes of acute scrotum, point-of-care ultrasound agreed with final diagnosis in 70% (95% confidence interval [CI] 62-78%) of cases, and more experienced point-of-care ultrasound users displayed higher agreement with final diagnosis. Point-of-care ultrasound results were generated a median of 73 min (Q1 = 51, Q3 = 112) before radiology department ultrasound results. DISCUSSION: Scrotal POCUS performed by pediatric emergency physicians appears to be an accurate tool to detect testicular torsion in children with acute scrotum and saves time compared with radiology ultrasound. The study results may not be generalizable to hospitals without a multidisciplinary POCUS system for quality assurance and image sharing. Future work on POCUS for acute scrotum should investigate its impact on patient outcomes, cost-effectiveness, and family satisfaction. CONCLUSION: Point-of-care ultrasound by pediatric emergency physicians is accurate for detecting testicular torsion in children with acute scrotum and could expedite diagnosis of this time-sensitive condition.

Modified staged repair of bladder exstrophy: a strategy to prevent penile ischemia while maintaining advantage of the complete primary repair of bladder exstrophy.

INTRODUCTION: Penile ischemic injury is a reported catastrophic complication after complete primary repair of exstrophy (CPRE). Aiming to improve the bladder exstrophy-epispadias repair outcomes, the study institution adopted a modified staged exstrophy repair to incorporate the advantages of CPRE by avoiding concurrent epispadias repair and adding bilateral ureteral re-implantation and bladder neck tailoring (staged repair of bladder exstrophy with bilateral ureteral re-implantation [SRBE-BUR]) at the initial repair. It was hypothesized that such modifications minimize penile complications and prevent upper tract deterioration while enhancing bladder resistance and consequent capacity. Here, a comparative series of outcomes between CPRE and SRBE-BUR is reported. METHODS: A retrospective cohort study including all exstrophy-epispadias male neonates managed in the study institution from January 2000 to December 2014 was performed. Patients were divided into those who underwent CPRE-BUR (group 1) and SRBE-BUR (group 2) (Figure). Baseline characteristics, peri-operative data, and long-term surgical outcomes were collected and analyzed for between-group comparison. Fisher exact and Mann-Whitney U tests were performed for statistical analysis. RESULTS: A total of 21 eligible patients were included: 10 in group 1 and 11 in group 2. Baseline characteristics were comparable. Two patients in group 1 had intra-operative penile ischemic injury (one with subsequent penile tissue loss), whereas none of the group 2 patients had intra-operative complications. No significant difference between the groups was noted for operative time; however, significantly lesser blood loss was noted in group 2. Comparable long-term surgical outcomes such as additional surgical intervention, urinary continence, bladder capacity, vesicoureteral reflux, hydronephrosis and recurrent urinary tract infections (UTIs) were noted. In addition, although subjective, better penile length and cosmesis were achieved by staging the repair (Figure). CONCLUSION: The SRBE with bilateral ureteral re-implantation is a safe alternative for the repair of the exstrophy-epispadias repair as it prevents the catastrophic complication of penile tissue loss, while having comparable long-term outcomes with the CPRE. Delaying epispadias repair avoids penile injury besides possible improvement of its overall cosmesis.

Stent-related complications after hypospadias repair: a prospective trial comparing Silastic tubing and Koyle urethral stents.

INTRODUCTION: There is a paucity of data comparing urethral stents after hypospadias repair. The aim of this study is to compare Silastic tubing vs Koyle stents (Cook Medical), addressing outcomes related to stent-related complications, added visits to healthcare providers in the early postoperative period, and postoperative complications at clinic follow-up. MATERIALS AND METHODS: Following an alternate week allocation, 150 patients were prospectively assigned to have Silastic tubes (n = 76) and Koyle stents (n = 74) after hypospadias repair. Exclusion criteria included fistula repairs, drainage via alternative catheter, or stentless repairs. Silastic tubes were secured with 5-0 Prolene and removed during a planned clinic visit. Koyle stents were secured with 7-0 PDS and left to fall out spontaneously. Questionnaires capturing postoperative outcomes were completed. RESULTS AND DISCUSSION: Median age was 13 and 11 months in the Silastic and Koyle stent groups, respectively (P = 0.48). There was no statistically significant difference in hypospadias location. Blockage/kinking of stents occurred in 8% (n = 6) of the Silastic and 9% (n = 7) Koyle stent groups, P = 0.78. Although follow-up was short, there was no difference in fistula rate among the Silastic (21%, n = 14) versus Koyle stent group (17%, n = 11), P = 0.66. There was a twofold higher rate of emergency department (ED) visits in the Silastic (32%, n = 24) versus Koyle stent group (16%, n = 12), P = 0.03. Half of ED visits in the Silastic group were related to stents falling out before planned removal. The authors propose that Silastic stents falling out before the removal date may have led to increased parental anxiety and thus a visit to the ED. With improved parental education, the authors propose that many of these visits may have been preventable. CONCLUSIONS: There were no significant differences in stent-related complications or fistula rate between the Silastic and Koyle stent groups. Although there were a twofold higher number of visits to the ED in the Silastic stent group, the authors propose that this was due to parental education rather than the stent itself.

Postoperative pain and analgesia administration in children after urological outpatient procedures.

INTRODUCTION: There are limited data about pain patterns, analgesic requirements and factors predicting opioid requirements of children undergoing outpatient urologic surgery. This prospective study aimed to assess recovery profiles and pain medication requirements. METHODS: Patients between 6 months and 12 years of age were recruited prospectively between December 2013 and June 2014. Demographic and operative characteristics were collected. Following discharge home, the parents were asked to administer both acetaminophen and ibuprofen Q6H at a weight-adjusted dose, based on a schedule, until the end of postoperative day 2, and to administer the medication as required on postoperative day 3. Pain severity was recorded using validated pain scores (Face, Legs, Activity, Cry, Consolability/Parents' Postoperative Pain Measurement). A morphine prescription was provided for breakthrough pain. A Likert scale was used to assess parent's satisfaction with the pain management. RESULTS: A total of 249 patients were recruited, 111 patients (45%) returned appropriately completed surveys and were included in the final analysis. Mean age was 44.1 months (SD = 37.3). The performed procedures were orchidopexy (31), hypospadias repair (26), hernia/hydrocele repair (15), Fowler-Stephens procedure (13), meatoplasty (7), phalloplasty (4), scrotoplasty (1), circumcision (7), and diagnostic laparoscopy (5). After discharge home 17 patients (15.3%) received morphine. Mean utilization of non-opioid analgesia was 79% on postoperative day 1, 67% on day 2, 36% on day 3, and 2% on day 4. Parental satisfaction was high (92.0% satisfied/very satisfied). No patient, anaesthetic or surgical factors were associated with opioid use or prolonged need for postoperative analgesia. CONCLUSION: The combination of scheduled non-opioid medications for maintenance and opioids for breakthrough pain provided satisfactory pain control after outpatient urologic surgery in children. There were no specific patient, anesthetic or surgical factors that predicted postoperative opioid requirements.

Laparoscopic ureteral ligation (clipping): a novel, simple procedure for pediatric urinary incontinence due to ectopic ureters associated with non-functioning upper pole renal moieties.

OBJECTIVE: A simplified approach for the surgical management of symptomatic ectopic ureters, associated with a non-functioning upper moiety, with laparoscopic ureteric clipping is presented in this research paper. MATERIALS AND METHODS: Prospectively collected data on nine consecutive girls with ectopic ureters associated with urinary incontinence who underwent laparoscopic clipping between February 2011 and December 2013. Surgical technique consisted of cystoscopy and insertion of ureteral catheter in the lower pole ureter to aid in identification and clipping of the ectopic ureter, which was achieved by standard trans-peritoneal laparoscopy. RESULTS: Median age was eight years (range 4-17 years). Diagnosis was based on clinical findings, which were supported by: ultrasound (US), nuclear scans and magnetic resonance urography in Cases 9, 8 and 5, respectively. Bilateral complete duplication was present in two patients; the combination of cystoscopy and laparoscopy allowed adequate identification of the ectopic ureter causing incontinence in both. All nine patients were immediately dry after surgery and remain asymptomatic after a maximum follow up of 27 months. Eight out of nine patients had developed some degree of asymptomatic upper pole hydronephrosis on follow-up US. CONCLUSION: Laparoscopic clipping holds promise as a simple alternative to other more-complex surgical procedures in the treatment of incontinence due to an ectopic ureter. Despite favorable and encouraging initial results, further follow up is warranted in order to determine the fate of expected associated upper-pole hydronephrosis.

Single-center experience with botulinum toxin endoscopic detrusor injection for the treatment of congenital neuropathic bladder in children: effect of dose adjustment, multiple injections, and avoidance of reconstructive procedures.

OBJECTIVE: Since 2007, intra-detrusor OnabotulinumtoxinA (OnabotA) injections have been selectively offered at our institution for cases in which maximal anticholinergic therapy failed or was not tolerated. Herein we present our experience with this approach. MATERIALS AND METHODS: We prospectively obtained data on 17 patients who underwent OnabotA injections over a 4-year period. Demographic information, number of injections, and dose delivered were captured. Children were monitored with baseline and post-injection renal ultrasound, urodynamics, and assessed for side effects, satisfaction, and symptom improvement. RESULTS: Forty-three sessions were performed with injections given every ∼ 6 months. Mean patient age was 10.7 years (range, 3-17). Compared with baseline, after the first injection, mean bladder capacity adjusted for age and compliance improved by 27% (p = 0.039) and 45.2% (p = 0.041), respectively. After subsequent injections, these values increased to 35.7% (p = 0.043) and 55.1% (p = 0.091), respectively. Out of 13 symptomatic patients, ≥ 50% improvement was reported in ten (76.9%) and complete resolution in seven (53.8%). However, all three patients in whom the maximum dose of OnabotA was reduced from 300 to 200 units complained of recurrent symptoms. Fourteen children avoided surgical reconstruction as a second line of treatment. Overall patient/parental reported satisfaction rate was 70.6% (12/17). CONCLUSIONS: Intra-detrusor OnabotA injection is a promising intervention for management of neuropathic bladder in selected patients. Our data demonstrate improvement in symptoms and urodynamic parameters. Although an optimal dose has not been determined for children, we found optimal response with a maximum administration of OnabotA up to 300 units.

Comparison between laparoscopic and open radical nephrectomy for the treatment of primary renal tumors in children: single-center experience over a 5-year period.

OBJECTIVES: To compare the outcomes of laparoscopic nephrectomy (LN) with open radical nephrectomy (ORN) in the management of consecutive pediatric neoplasms. PATIENTS AND METHODS: Retrospective cohort study of consecutive children treated for primary renal tumors between 2006 and 2011, segregated based on surgical modality (LN/ORN). Pre-, intra- and postoperative data and outcomes were collected. RESULTS: Demographics from the 45 patients (13 LN, 32 ORN) were similar, and tumors in the LN group were smaller [6.59 ± 1.8 cm vs. 10.99 ± 2.99 cm ORN (p < 0.05)]. Six patients had preoperative chemotherapy (two LN, four ORN). No tumor ruptures occurred with either technique. Wilms tumor (seven LN, 24 ORN) was the most common diagnosis, followed by renal cell carcinoma (four LN, four ORN). Procedure length was similar between groups (282 ± 79 LN, 263 ± 81 min ORN). Mean length of stay was significantly shorter for LN (2.9 vs. 5.9 days; p = 0.002). Postoperative narcotic requirements and use of nasogastric tube were higher in the ORN group. After a median follow-up of 18 (LN) and 33 months (ORN), 1 and 4 recurrences occurred, respectively. CONCLUSIONS: LN is an attractive alternative to open surgery in carefully selected cases of pediatric renal tumors. Procedure length and incidence of intra-operative rupture were not increased, while post-operative recovery and hospital stay were shorter for LN. Longer follow-up is mandatory to confirm comparable oncological outcomes to ORN.

Urethral compliance in hypospadias operated by tubularized incised urethral plate (TIP) with and without a dorsal inlay graft: an experimental controlled study.

OBJECTIVE: Abnormal uroflowmetries are common after tubularized incised plate urethroplasties (TIP), perhaps due to low compliance. We hypothesized that (1) abnormal uroflowmetries after TIP might be caused by segmental lower compliance; (2) by adding a graft to the raw area in the incised plate (TIPG), compliance might be improved by preventing secondary intention healing of the dorsal incision. METHODS: A standardized penectomy was performed in 27 adult male rabbits: 9 normal non-operated controls (G1), 6 weeks after TIP (G2: n = 9) or TIPG (G3: n = 9). A standardized isolated segment (including the whole urethroplasty in G1 and G2) was progressively distended with air (1, 2 and 3 ml) in the 3 groups. The respective intraluminal pressures were measured with a tensiometer. RESULTS: Pressure measurements were feasible and reproducible for this model. Mean pressures tended to be higher in the experimental groups (G1: 59.7 mmHg vs. G2: 79.6 mmHg vs. G3: 100.1 mmHg for 1 ml injections; G1: 233.1 mmHg vs. G2: 241 mmHg vs. G3: 308.4 mmHg for 2 ml injections and G1: 457.3 mmHg vs. G2: 429 mmHg vs. G3: 520 mmHg for 3 ml injections) without reaching the statistical significance. CONCLUSION: In this model, the elasticity of the TIP or TIPG neourethras tended to be reduced when compared to controls. The placement of an inlay graft on the dorsal incised area did not increase the compliance. This model allows the measurement of segmental intraluminal urethral pressures generated by controlled air distension and may be a useful tool to evaluate the experimental urethroplasty models.

The predictive value of diagnostic imaging for histological lesions of the upper poles in duplex systems with ureteroceles.

OBJECTIVE: To compare the diagnostic imaging findings with the histological lesions in upper pole nephrectomy (UPN) specimens of duplex system ureteroceles, using renal ultrasonography (US) and nuclear renal scintigraphy. PATIENTS AND METHODS: Between 1992 and 2000, 86 patients with a ureterocele in a duplex system underwent surgery. The results from US were reviewed in 84 patients by a radiologist, for echogenicity, parenchymal thinning and hydronephrosis; 77 nuclear renal scans describing the differential function of the upper poles were also reviewed. Fifty-five patients underwent UPN (25 antenatal, 30 postnatal; 18 intravesical, 37 extravesical) and the specimens were available for independent review by a pathologist, describing five histological categories, i.e. chronic interstitial inflammation, fibrosis, tubular atrophy, glomerulosclerosis and dysplasia. Histological lesions were categorized as severe (> 25%) or minimal (

The use of tolterodine in children after oxybutynin failure.

OBJECTIVE: To assess the safety and efficacy of tolterodine tartrate prescribed to children who previously failed to tolerate oxybutynin chloride. PATIENTS AND METHODS: We reviewed 34 children, followed for>1 year, who were prospectively crossed-over from oxybutynin to tolterodine because of side-effects. The initial diagnosis was dysfunctional voiding in 31 patients. All patients were placed on a behavioural modification protocol. When their symptoms did not improve after 6 months, treatment with an anticholinergic agent was considered. Urodynamic studies were conducted in 20 patients, confirming uninhibited contractions in 19. The remaining 14 patients were empirically started on antimuscarinic or anticholinergic agents. The 34 patients were treated with oxybutynin for a median (range) of 6 (2-84) months. When significant side-effects were reported, they were crossed over to tolterodine. The efficacy of tolterodine was assessed as defined by the International Children's Continence Society, with tolerability assessed and side-effects documented using a questionnaire. RESULTS: The mean age at the first dose of tolterodine was 8.9 years; the dose was 1 mg twice daily for 12 patients and 2 mg twice daily for 22. The median treatment with tolterodine was 11.5 months, with 20 (59%) patients reporting no side-effects; six described the same but tolerable side-effects as with oxybutynin. Eight patients discontinued tolterodine because of side-effects after a median (range) of 5 (1-11) months. The efficacy of tolterodine was comparable with that of oxybutynin, as reported by the questionnaire and voiding diaries. The reduction in wetting episodes at 1 year was> 90% in 23 (68%), more than half in five and less than half (or failure) in six patients. CONCLUSION: Tolterodine is tolerated well in children. In this subgroup of patients who could not tolerate oxybutynin, 77% were able to continue tolterodine treatment with no significant side-effects.

Tunica vaginalis for correcting penile chordee in a rabbit model: is there a difference in flap versus graft?

PURPOSE: We compared tunica vaginalis applied as a flap versus a graft for covering defects in the ventral tunica albuginea in a rabbit model. MATERIALS AND METHODS: We used 18 New Zealand White rabbits in the study. The urethra was mobilized off of the corpus cavernosum. A defect was created in the ventral aspect of the tunica albuginea by excising a 1 x 0.5 cm. rectangular area. The defect was covered by the testicular surface of tunica vaginalis as a vascularized flap in 9 animals and as a graft in 9. At 2, 6 and 12-week intervals 3 animals per group were sacrificed. Transverse sections of the penis at the repair site were stained with hematoxylin and eosin, and Masson's trichrome for microscopy. RESULTS: Autopsy revealed no contracture in any of the tunica vaginalis flaps. In contrast, the tunica vaginalis grafts had contracted by a mean of 22% (range 20% to 25%) at 2, 38% (range 30% to 44%) at 6 and 42% (range 38% to 48%) at 12 weeks. Microscopic examination of the tunica vaginalis flaps showed evidence of an intact blood supply and viable cremasteric muscle layer but no evidence of necrosis. Collagen remodeling and maturation was noted at 12 weeks. In tunica vaginalis grafts there was evidence of necrosis of all tunica vaginalis layers at 2 weeks with granulation tissue and active fibrosis at the periphery. At 6 and 12 weeks most necrotic tissue was replaced by fibrosis. Osseous metaplasia was identified in 1 graft at 12 weeks. CONCLUSIONS: The optimal use of tunica vaginalis for correction of chordee is as a flap rather than as a free graft. Grafts were associated with significant necrosis and contracture, of which neither was associated with flaps.

Extracellular matrix gene responses in a novel ex vivo model of bladder stretch injury.

PURPOSE: Congenital bladder outlet obstruction from either mechanical or functional causes often results in clinical bladder fibrosis. We tested the hypothesis that early molecular changes relevant to fibrosis occur in response to stretch injury of the bladder wall and that specific extracellular matrix receptors mediate some of these responses. Furthermore, we introduce a novel ex vivo model of bladder injury which has advantages over previously described in vivo bladder outlet obstruction models by uniquely interrogating molecular responses to bladder distention. MATERIALS AND METHODS: The bladders of Sprague Dawley rats were hydrodistended transurethrally, the ureters and bladder neck were ligated, and the whole bladder was excised and incubated in culture medium in the distended state. At fixed time-points control and stretch bladders were snap frozen, RNA was extracted, and semiquantitative reverse transcription polymerase chain reaction for collagens I, III and XII, and RHAMM (receptor for hyaluronic acid) messenger (m) RNA was performed to establish trends in stretch related gene expression. Bladder specimens were also subjected to routine histological evaluation. RESULTS: An average 3-fold reduction in collagen I mRNA expression was seen with 8 hours of static stretch (p <0.05). Bladder stretch increased collagen III mRNA levels approximately 2.5-fold (p <0.05). Whole bladder collagen XII and RHAMM mRNA were elevated as much as 5-fold (p <0.05) with stretch. Blocking RHAMM function significantly attenuated these matrix gene responses (p = 0.01 to 0.005). CONCLUSIONS: The ex vivo model of whole bladder stretch is viable and easily reproducible for the study of molecular pathophysiological mechanisms contributing to maladaptive bladder disease. Furthermore, collagen gene transcription is revealed to be rapidly responsive to stretch injury of the bladder. Intact RHAMM receptor function is involved in these responses. Elucidation of the intermediate steps in this response to injury may allow for the development of novel therapeutic strategies which may prevent pathological matrix remodeling seen in clinical bladder disease.

A population based analysis of continence outcomes and bladder exstrophy.

PURPOSE: Whereas the literature on bladder exstrophy is replete with outcomes of specific continence surgical procedures in highly select patients, there are no data on the outcomes related to continence for a complete exstrophy population, which is more comprehensive with respect to a variety of surgical procedures performed to achieve continence. To provide urologists and patients with an overview of potential continence outcomes devoid of any selection bias, we report on a comprehensive exstrophy population, focusing on the various procedures required for urinary continence. MATERIALS AND METHODS: We reviewed the charts of all patients with bladder and cloacal exstrophy who underwent a staged repair to achieve urinary continence at a single institution between 1988 and 1998. Urinary continence was then correlated to the types of surgical procedures, and subgroup analysis for predictors of urinary continence was performed. The type of bladder neck reconstruction allowed subgrouping cases into group 1-bladder neck reconstruction only, group 2-bladder neck reconstruction with augmentation and/or appendicovesicostomy and group 3-bladder neck closure. RESULTS: Of the 43 patients identified 26 were male, 4 had cloacal exstrophy and 3 had complex exstrophy variants with ectopic hindgut and spina bifida. Groups 1 to 3 comprised 9, 15 and 19 patients with urinary continence rates of 56%, 67% and 100%, respectively. The age at which patients became continent was delayed in groups 2 and 3 (8.2 and 8.7 years, respectively) compared to group 1 (4.8). Of all the potential variants measured gender was the strongest predictor of continence with 94% of females versus 69% of males achieving it. Of the males those with (57%) compared to those without (83%) a history of bladder neck stenosis or paraexstrophy flaps had worse continence. Repeat bladder neck reconstruction was only successful in 23% of patients. CONCLUSIONS: All patients can be rendered continent but many may achieve this successful outcome by other procedures following initial bladder neck reconstruction. When managing failed bladder neck reconstruction, the type of surgical repair chosen may need to address the need for enhanced bladder storage and the issue of potential bladder augmentation. The advances made in the treatment of the epispadiac urethra may now facilitate clean intermittent catheterization. Earlier recognition of the need for adjunctive storage procedures in addition to bladder neck reconstruction may facilitate the timing of providing enhanced continence, independence and self-esteem, and do so with fewer operative procedures. We speculate that the current complete urethral and bladder repair in newborns will add further to the storage functions of the native bladder tissues and improve the potential of achieving more effective bladder outlet control.

Reliability of the pediatric dysfunctional voiding symptom score in monitoring response to behavioral modification.

PURPOSE: We previously evaluated the performance of a newly devised dysfunctional voiding symptom score to quantify abnormal voiding behaviors in children. The symptom score ranges from 0 to 30 with higher scores indicating greater severity. In this study, we test the performance of the symptom score in monitoring effectiveness and compliance with a program of behavioral modification. MATERIALS AND METHODS: One hundred four patients (age 3-10 years) were clinically diagnosed as having dysfunctional voiding (DV). At initial visit, after their baseline DV symptom scores were tabulated, they were introduced to a program of behavioral modification that included both verbal and written instructions. After an average follow up of 5 months, all families were mailed questionnaires to: a) assess whether the child was compliant with bladder retraining, and b) request the completion of a second DV symptom-scoring sheet. The change in symptom score was correlated with treatment compliance. Statistical analysis of the data was done using non-parametric method (Mann-Whitney U test). RESULTS: Forty-eight out of 104 children (46%) completed the mailed questionnaires. Twenty-eight (Group A1) were compliant with the behavioral modification program, and the remaining 20 children (Group A2) were not compliant. Although the median score at initial evaluation was similar in both groups (15 versus 14.5 respectively), scores in last follow up were significantly lower in Group A1 than the initial scores (6 versus 14.5 respectively). The scores in last follow-up in Group A2 were not significantly different from their initial symptom scores (median 11 versus 14.5 respectively). CONCLUSION: The DV symptom score reliably and quantitatively reflects improvement in voiding symptoms in patients compliant with behavioral modification. Patients non-compliant with a bladder retraining program may be identified by lack of decrease in their DV symptom score. Key Words: voiding dysfunction, pediatric, behavioral modification, symptom score

Regeneration of functional bladder substitutes using large segment acellular matrix allografts in a porcine model.

PURPOSE: We previously reported on the short-term (4 weeks) morphometric analysis of a large bladder acellular matrix allograft used as a bladder bioprosthesis (average size 24 cm.2). We demonstrated cellular repopulation through the entire thickness of the graft. We now present the long-term (12 weeks) morphometric results of graft regenerated porcine bladders using segments measuring an average of 40 cm.2. MATERIALS AND METHODS: Bladders harvested from pigs were subjected to detergent and enzymatic extractions to render them acellular. Partial cystectomy was performed in 21 pigs and the defect was repaired with a bladder acellular matrix allograft (average size 40.52 cm.2). Of the animals 8 were sacrificed at 1, 2 and 4 weeks and 13 were sacrificed at 8 and 12 weeks. To evaluate cellular repopulation and matrix reorganization the native bladder and graft were analyzed using standard histological and immunofluorescent techniques. To evaluate for calcium deposits in the grafts a radiological evaluation of the graft was performed after explantation. RESULTS: All animals survived the surgical procedure and there were no significant urinary leaks. No stones were noted in any of the bladders. At 1 week there was a diffuse infiltration with acute inflammatory cells. At 2 weeks the luminal surface of the graft was lined with a single layer of urothelium, and there was stromal infiltration with unorganized smooth muscle cells and angiogenesis. At 4 weeks the urothelium was multilayered with organizing groups of smooth muscle cells and angiogenesis. At 8 and 12 weeks there was repopulation throughout the bladder acellular matrix allograft implant with all native cellular components participating. CONCLUSIONS: We present evidence that large patch bladder acellular matrix allograft implantation is technically feasible and may prove to be a viable surgical alternative to bladder augmentation with intestinal segments. Its advantages may include the potential for complete and functional regeneration of a bladder substitute.

The dysfunctional voiding scoring system: quantitative standardization of dysfunctional voiding symptoms in children.

PURPOSE: Academic research on pediatric nonneurogenic voiding dysfunction has long been hampered by the lack of a standardized reporting system for voiding symptoms. We evaluated the performance of a newly devised, objective instrument to quantify or grade the severity of abnormal voiding behaviors of children. MATERIALS AND METHODS: There were 10 voiding dysfunction parameters that were assigned scores of 0 to 3 according to prevalence, and possible total scores ranged from 0 to 30. The Dysfunctional Voiding Symptom Score was completed by 2 groups of patients. Group 1 consisted of patients 3 to 10 years old presenting to the pediatric urology clinic with a history of diurnal urinary incontinence, urinary tract infections or abnormal voiding habits. Group 2 consisted of an age matched cohort with no history of urological complaints presenting to hospital clinics outside of urology. Patients diagnosed with organic or anatomical disease, such as posterior urethral valves or meningomyelocele, were excluded from our analysis. RESULTS: Group 1 consisted of 104 patients (female-to-male ratio 4:1) with a median symptom score of 14 and group 2 consisted of 54 patients (female-to-male ratio 1.3:1) with a median score of 4. The dysfunctional voiding odds ratio was 2.93 for females compared to that of males. Using receiver operating characteristics the optimum cutoff score was 6.026 (sensitivity 92.77% and specificity 87.09%) for females and 9.02 (sensitivity of 80.95% and specificity of 91. 30%) for males. In addition, we found certain questions to be more reflective than others of dysfunctional voiding symptoms in our population. CONCLUSIONS: The Dysfunctional Voiding Symptom Score appears to provide accurate and objective, that is, numerical, grading of voiding behaviors of children. Comparative research studies of dysfunctional voiding diagnosis and response to therapy as well as objective measurements of treatment efficacy and outcomes analysis should be aided greatly by this system.

Acellular bladder matrix allografts in the regeneration of functional bladders: evaluation of large-segment (> 24 cm) substitution in a porcine model.

OBJECTIVES: To evaluate the use of a large-segment (> 24 cm2) bladder substitution with porcine bladder acellular matrix allograft (BAMA) in a large animal model. Materials and methods Bladders were harvested from pigs at the time of necropsy and subjected to detergent and enzymatic extractions to render them acellular. The BAMA produced had the surgical handling and suture-retaining properties of normal bladder tissue. Six pigs had BAMA segments implanted under general anaesthesia, through a low midline abdominal incision and after partial cystectomy. The defect was repaired with a BAMA patch (mean size 43.88 cm2, range 12-72), with no urinary diversion. Two animals each were then killed at 9, 16 and 30 days and the bladders explanted. The native bladder and BAMA patch were analysed morphometrically to evaluate cellular re-population and matrix re-organization. RESULTS: All animals survived surgery; there were no urinary leaks and no stones detected in any of the bladders. At 9 days there was a diffuse infiltration with acute inflammatory cells, but no areas of necrosis. There were isolated areas of smooth muscle cell (SMC) infiltration of the BAMA. At 16 days the luminal surface was lined with a single layer of urothelium, there was stromal infiltration with disorganized SMC and angiogenesis, with mature vessels in the BAMA patch. At 30 days the urothelium was multilayered with organizing groups of SMCs and angiogenesis. The highest cell density was at the periphery of the repopulated BAMA patch, decreasing towards the centre. CONCLUSIONS: The implantation of large patches of BAMA is technically feasible and may prove to be a viable surgical alternative to bladder augmentation with intestinal segments. The advantages of BAMA include the potential for complete and functional regeneration of a bladder substitute. This model provides a tool with which to obtain a better understanding of the cellular and molecular aspects of matrix re-population.

Initial experience with endoscopic holmium laser lithotripsy for pediatric urolithiasis.

PURPOSE: Due to the unavailability of suitable pediatric instruments children have not benefited from advances in endoscopic lithotripsy. This limitation may be overcome by the holmium: YAG laser. We evaluated the indications for, and efficacy and complications of holmium:YAG laser lithotripsy. MATERIALS AND METHODS: We retrospectively reviewed all cases of laser lithotripsy. Access to the calculus was antegrade or retrograde. A solid state holmium:YAG laser was used. RESULTS: Eight patients 4 to 14 years old underwent laser lithotripsy during the study period. Average calculous surface area was 357.13 mm.2 (range 14 to 1,645). Five patients required 1 procedure to render them stone-free, while the remaining 3 required multiple procedures. No complications were associated with laser lithotripsy. CONCLUSIONS: The ability of the holmium:YAG laser to pulverize urinary calculi makes it an alternative choice for lithotripsy. In our series all patients are stone-free with stable renal function. The advantages of the holmium:YAG laser are that it may be precisely applied via small fibers, and it pulverizes calculi with minimal scattering of energy and retropulsion of the calculus, decreasing trauma to tissues at the perioperative site. There is also a lower risk of residual fragments, which is associated with a lower incidence of calculous regrowth. Holmium: YAG laser is safe and effective for treating pediatric urolithiasis.

The hyaluronic acid receptor RHAMM is induced by stretch injury of rat bladder in vivo and influences smooth muscle cell contraction in vitro [corrected].

PURPOSE: Loss of bladder compliance from hypercontractility and fibrosis may represent an injury response to excessive intravesical pressure. Together, interactions between cell and extracellular matrix components regulate cell response to injury and extracellular matrix remodeling. The receptor for hyaluronic acid mediated motility (RHAMM) is a recently described hyaluronic acid binding protein known to influence multiple types of cell extracellular matrix interaction in development, injury and cancer. We evaluate the role of RHAMM in mediating early events in bladder stretch injury. MATERIALS AND METHODS: An acute stretch injury model was used. The rat bladder was injured by hydrodistention inducing gross hematuria. Tissues were analyzed for temporal and spatial expression of RHAMM in the mucosa and detrusor regions by immunostaining, western and reverse transcriptase polymerase chain reaction analyses. The contractile activity of smooth muscle cell primary cultures was analyzed using a gel contraction assay in the presence of peptide fragments known to block RHAMM function. RESULTS: Acute hydrodistention caused immediate and significant injury to the bladder, with fracturing of smooth muscle cell bundles, edema and hemorrhage. RHAMM immunolocalized to the mucosa and detrusor within 2 hours of injury, peaking by 5 to 10 hours. A shift from low molecular weight (55 kD.) to high (120 kD.) receptor isoforms was prominent during the peak expression period noted by immunolocalization. RHAMM messenger ribonucleic acid increased only slightly (40%) by 5 hours after injury. Smooth muscle cell primary cultures actively initiated and maintained the contraction of collagen gels by more than 75% of baseline in vitro. Blocking RHAMM function significantly inhibited the ability to less than 25% of smooth muscle cells to contract the gels in vitro. CONCLUSIONS: Increased expression of RHAMM is an early event precipitated by stretch injury to the bladder. Since extracellular matrix hyaluronic acid is found early in tissue repair responses, its receptor RHAMM may be mediating initial bladder responses to stretch injury, some of which (contraction) may be experimentally blocked in vitro. Since the receptor directly regulates protein kinase signaling which in turn mediates smooth muscle cell contraction and collagen synthesis, further studies of RHAMM function in bladder pathology are warranted.