Bruno Leslie

Long-Term Followup and Time to Event Outcome Analysis of Continent Catheterizable Channels

PURPOSE Creation of a continent catheterizable channel has facilitated the treatment of patients undergoing lower urinary tract reconstruction. We present outcomes and complications of a single center series of continent catheterizable channels followed out to 15 years. MATERIALS AND METHODS We retrospectively reviewed medical records of all children who underwent continent catheterizable channel (Mitrofanoff and Monti) between 1992 and 2007. Collected data included age, underlying diagnosis, associated procedures, stoma site, conduit type (appendix or reconfigured bowel), time to complications and need for subsequent surgical revisions. RESULTS We identified 71 girls and 98 boys who underwent surgery at a mean age of 7.5 years (range 6 months to 22 years) and were subsequently followed for a mean of 5.8 years (8 months to 15 years). Underlying diagnoses included neurogenic bladder (36% of patients), bladder exstrophy (25%), epispadias (6%) and posterior urethral valves (6%). Concurrent procedures were conducted in 71% of cases, including augmentation (35%) and bladder neck plasty (22%) or closure (8%). Surgical revision was performed in 39% of patients, including stomal revision (18%), redo operation (8%), bulking agent injection (8%) and prolapse correction (4%). Although an initial peak was followed by a relatively stable complication-free period, delayed problems were detected on long-term followup. No statistically significant differences in complication rates were noted when comparing use of appendix and reconfigured bowel or different stoma locations. CONCLUSIONS Despite an initial decrease in complications soon after continent catheterizable channel creation, late problems appeared on long-term evaluation. In our experience no specific factor predicted the likelihood of complications. Nevertheless, despite the need for surgical revision, good functional outcomes were evidenced in this series.

Surgical Treatment of High Urogenital Sinuses Using the Anterior Sagittal Transrectal Approach: A Useful Strategy to Optimize Exposure and Outcomes

PURPOSE Surgical management of the high urogenital sinus remains challenging. The anterior sagittal transrectal approach provides optimal exposure, facilitates vaginal dissection and separation from the urethra, and allows reconstruction of the bladder neck musculature. In this study we report our initial experience with this technique. MATERIALS AND METHODS We performed a retrospective review of a 6-year multi-institutional experience treating patients with a urogenital sinus anomaly using the anterior sagittal transrectal approach without preoperative colostomy or prolonged postoperative fasting. Variables analyzed included patient age, associated malformations, the need for additional procedures and surgical outcomes. RESULTS A total of 23 children with a mean age of 2.3 years (range 3 months to 17 years) who underwent surgery between 2003 and 2010 were included in the study. Mean followup was 3.4 years (range 14 months to 7 years). All children had a high urogenital sinus with (16) or without (7) congenital adrenal hyperplasia. There were 3 isolated cases treated with additional procedures. Only 1 anterior sagittal transrectal approach related complication was encountered when a perineal infection developed in a child and required temporary diverting colostomy without compromising the repair. There were no postoperative urethrovaginal fistulas. All toilet trained patients were continent for feces and most were voiding normally per urethra (21), except for 2 with associated urological malformations. There were 15 patients who underwent followup examination under anesthesia, and demonstrated separate urethral and vaginal openings. CONCLUSIONS The anterior sagittal transrectal approach provides excellent exposure for the management of a high urogenital sinus, facilitating the separation of urogenital structures. Good outcomes in terms of urinary/fecal continence as well as the absence of urethrovaginal fistulas were achieved in the majority of cases, supporting its consideration for the surgical management of this congenital abnormality.

Critical Outcome Analysis of Staged Buccal Mucosa Graft Urethroplasty for Prior Failed Hypospadias Repair in Children

PURPOSE Although staged buccal mucosa graft urethroplasty is a well accepted technique for salvage urethroplasty, there are few reports on this procedure for redo hypospadias repair in children. MATERIALS AND METHODS We reviewed patients who underwent staged buccal mucosa graft urethroplasty for redo hypospadias repair. Age, quality of graft before tubularization, meatal position, presence of balanitis xerotica obliterans and complications were recorded. RESULTS A total of 30 patients underwent 32 repairs during a 5-year period. Mean age at first stage was 7 years (range 1 to 17) and mean interval between stages was 9.3 months (5 to 13). Mean followup after second stage was 25 months (range 10 to 46). Meatal position before first stage was proximal in 44% of patients, mid shaft in 39% and distal in 16%. Nine patients had biopsy proved balanitis xerotica obliterans. There were no donor site complications. Four patients underwent a redo grafting procedure. Complications after second stage occurred in 11 of 32 repairs (34%), consisting of urethral stenosis in 5, glanular dehiscence in 3 and urethrocutaneous fistula in 3. A third of the patients had some degree of graft fibrosis/induration after the first stage. These patients were prone to more complications at second stage (9 of 11, 82%), compared to patients without these unfavorable findings (4 of 21, 19%; p<0.001). Presence of balanitis xerotica obliterans and meatal position were not significant factors associated with adverse outcomes. CONCLUSIONS Staged buccal mucosa graft urethroplasty is a suitable technique for salvage urethroplasty. Complications after second stage were seen in approximately a third of patients, mainly those with fibrotic/indurated grafts.

Mammalian Target of Rapamycin (mTOR) Induces Proliferation and De-Differentiation Responses to Three Coordinate Pathophysiologic Stimuli (Mechanical Strain, Hypoxia, and Extracellular Matrix Remodeling) in Rat Bladder Smooth Muscle

Maladaptive bladder muscle overgrowth and de-differentiation in human bladder obstructive conditions is instigated by coordinate responses to three stimuli: mechanical strain, tissue hypoxia, and extracellular matrix remodeling.( 1,2) Pathway analysis of genes induced by obstructive models of injury in bladder smooth muscle cells (BSMCs) identified a mammalian target of rapamycin (mTOR)-specific inhibitor as a potential pharmacological inhibitor. Strain-induced mTOR-specific S6K activation segregated differently from ERK1/2 activation in intact bladder ex vivo. Though rapamycins antiproliferative effects in vascular smooth muscle cells are well known, its effects on BSMCs were previously unknown. Rapamycin significantly inhibited proliferation of BSMCs in response to mechanical strain, hypoxia, and denatured collagen. Rapamycin inhibited S6K at mTOR-sensitive phosphorylation sites in response to strain and hypoxia. Rapamycin also supported smooth muscle actin expression in response to strain or hypoxia-induced de-differentiation. Importantly, strain plus hypoxia synergistically augmented mTOR-dependent S6K activation, Mmp7 expression and proliferation. Forced expression of wild-type and constitutively active S6K resulted in loss of smooth muscle actin expression. Decreased smooth muscle actin, increased Mmp7 levels and mTOR pathway activation during in vivo partial bladder obstruction paralleled our in vitro studies. These results point to a coordinate role for mTOR in BSMCs responses to the three stimuli and a potential new therapeutic target for myopathic bladder disease.

Clinical Evolution of Vesicoureteral Reflux Following Endoscopic Puncture in Children With Duplex System Ureteroceles

PURPOSE We studied the clinical evolution of vesicoureteral reflux after endoscopic puncture of ureterocele in pediatric duplex systems. MATERIALS AND METHODS We retrospectively reviewed charts of children with duplex system ureteroceles treated between 1992 and 2007. We analyzed patient age, prenatal diagnosis, urinary tract infection at presentation, differential renal function and preoperative vesicoureteral reflux. The fate of associated vesicoureteral reflux after endoscopic puncture of ureterocele was specifically addressed. RESULTS We analyzed 60 patients with a mean age of 12 months, of whom 32 (52%) were diagnosed prenatally and 40 (66%) presented with a urinary tract infection. The majority of ureteroceles were ectopic, and pre-puncture vesicoureteral reflux was seen in 40 patients (67%). Postoperative voiding cystourethrogram was performed in 50 cases. New onset of vesicoureteral reflux occurred postoperatively in 24 patients (40%), mainly ipsilateral to the lower pole or contralaterally. Spontaneous vesicoureteral reflux resolution or improvement occurred in 16 of 22 patients (72%) observed after primary endoscopic puncture of ureterocele. Surgical intervention after endoscopic puncture of ureterocele was performed in 25 patients (42%), of whom 9 underwent more than 1 reparative procedure. CONCLUSIONS Vesicoureteral reflux after endoscopic puncture of ureterocele may occur in the ipsilateral upper or lower poles, or in the contralateral renal segments. Therefore, the reflux is not necessarily related to the puncture itself. Vesicoureteral reflux after endoscopic puncture of ureterocele can resolve spontaneously in a significant number of patients. Therefore, initial management by close surveillance is warranted. Considering the simplicity of the procedure, our findings support that endoscopic puncture of ureterocele is an attractive alternative for the initial management of pediatric duplex system ureteroceles.

Analysis of Decisional Conflict Among Parents Who Consent to Hypospadias Repair: Single Institution Prospective Study of 100 Couples

PURPOSE Although obtaining informed consent for distal hypospadias repair is common practice, little is known about the uncertainty or conflict between consenting parents faced with this decision. We systematically evaluated decisional conflict between parents who elected to have their child undergo hypospadias surgery. MATERIALS AND METHODS A total of 100 couples who were counseled about treatment options agreed to participate. Using a validated questionnaire, the Decisional Conflict Scale, we prospectively collected data on decisional conflict demographics, preference for circumcision, education level and prior knowledge about hypospadias. RESULTS All parents elected surgical repair. Evidence of decisional conflict was encountered in 28% of participants (score less than 25 in 72%, 25 to 37.5 in 23.5%, greater than 37.5 in 4.5%). No statistically significant differences among parents were noted for total score (mean ± SD 16.1 ± 12 in mothers and 18.3 ± 12.6 in fathers) or subscales, except the informed subscale (mean ± SD 16.7 ± 14.3 in mothers and 21.1 ± 16.6 in fathers). Parental self-report of prior knowledge about hypospadias and preference for neonatal circumcision correlated with lower Decisional Conflict Scale scores (p = 0.02 and p <0.01, respectively). No statistical association was found between score and parental education level (p = 0.7) or expertise of the counselor (staff vs pediatric urology fellow, p = 0.4). CONCLUSIONS These data describe the level of decisional conflict in couples agreeing to proceed with hypospadias repair, with no evidence of significant discrepancy between them. The novel description of factors related to decreased decisional conflict might help focus efforts aimed at minimizing difficulties encountered during the decision making process.

Outcome of antibiotic prophylaxis discontinuation in patients with persistent vesicoureteral reflux initially presenting with febrile urinary tract infection: time to event analysis.

PURPOSE The use of antibiotic prophylaxis for preventing urinary tract infections has recently been called into question. Some studies support discontinuation of antibiotic prophylaxis in selected groups of children with vesicoureteral reflux. We report on the outcome of this practice in a cohort of patients assembled based on initial presentation with a febrile urinary tract infection. MATERIALS AND METHODS We retrospectively reviewed records of patients with persistent vesicoureteral reflux without symptoms suggestive of dysfunctional elimination who discontinued antibiotic prophylaxis after being toilet trained. Exclusion criteria consisted of secondary reflux and previous surgery for vesicoureteral reflux. End points included development of febrile urinary tract infections, renal abnormalities on followup ultrasound and need for further interventions. Infection-free survival was analyzed using the Kaplan-Meier method and compared using the log rank and Coxs tests. RESULTS We evaluated 84 girls and 26 boys with a mean age of 5.4 years. Febrile urinary tract infections developed in 10 girls and 1 boy at an average of 17.2 months after discontinuation of antibiotic prophylaxis. In a time to event analysis group comparison showed no significant differences when patients were stratified by gender (p = 0.22), age at antibiotic prophylaxis discontinuation (p = 0.14) or disease laterality (p = 0.23). However, a significant difference was found in number of patients with high grade vesicoureteral reflux (III to V, p = 0.05) and development of symptoms suggestive of bladder/bowel dysfunction (p <0.01). CONCLUSIONS Our data support antibiotic prophylaxis discontinuation in the majority of patients with persistent vesicoureteral reflux who initially present with a febrile urinary tract infection, once their elimination habits have been optimized. Those with high grade reflux appear to be at increased risk for recurrent urinary tract infections. Development of dysfunctional elimination symptoms appears to be a risk factor amenable to treatment.

Comparative Histological and Functional Controlled Analysis of Tubularized Incised Plate Urethroplasty With and Without Dorsal Inlay Graft: A Preliminary Experimental Study in Rabbits

PURPOSE We analyzed the histological and functional characteristics of the tubularized incised plate vs dorsal inlay graft urethroplasty in an experimental rabbit model. MATERIALS AND METHODS A total of 24 New Zealand male rabbits were randomly allocated into 4 groups, including sham operation, urethroplasty, tubularized incised plate urethroplasty and dorsal inlay graft urethroplasty. In the urethroplasty group the anterior urethral wall was half excised and the dorsal aspect was tubularized. In the tubularized incised plate group the same steps were followed but tubularization followed a longitudinal midline incision in the dorsal wall. In the dorsal inlay graft group the defect created by the dorsal incision was covered with an inner preputial graft. The animals were sacrificed at 4 and 8 weeks, respectively. The penis was immediately harvested for standardized passive flowmetry and subsequently fixed for histological staining. RESULTS The grafts took in all animals. The tubularized incised plate defect was bridged by urothelium while in the dorsal inlay graft group the preputial graft kept its original histological characteristics. There was a significant decrease in average flow in the urethroplasty group (1.6 ml per second) compared to that in the sham operated group (3.4 ml per second) and to the other groups (p <0.05). However, no significant difference in average flow was found for the tubularized incised plate and dorsal inlay graft groups (2.4 and 2.2 ml per second, respectively, p = 0.7). CONCLUSIONS In this short-term rabbit model dorsal inlay graft urethroplasty was feasible with good graft take and integration. Simple tubularization of a reduced urethral plate led to significantly decreased flow. Incision of the reduced plate with or without grafting improved the average flow. Findings in this experimental model do not support the superiority of dorsal inlay graft urethroplasty over tubularized incised plate urethroplasty in terms of urethral flow dynamics.

INCREASED BLADDER CAPACITY DEVELOPS WITH AGE, REGARDLESS OF INITIAL TREATMENT: A SINGLE CENTER 15-YEAR LONGITUDINAL FOLLOW-UP STUDY IN PATIENTS WITH POSTERIOR URETHRAL VALVES (PUV)

INTRODUCTION AND OBJECTIVE: It has been previously reported that early bladder overactivity in PUV boys might lead to detrusor failure and increased percentage of expected bladder capacity (PEBC) over time. It has also been hypothesized that urinary diversion (vesicostomy or ureterostomy) may adversely affect bladder function. To test these concepts, a longitudinal study following patients from birth to adolescence was conducted. METHODS: A chart review was conducted for 78 boys with PUV treated between 1985-1996. Pts who underwent bladder augmentation (n=12), children who were 10% of bladder capacity (PVR>10%) at initial and last FU and bladder emptying (clean intermintent catheterization CIC/double voiding) were recorded. Bladder capacity and PVR were measured by uroflowmetry and ultrasound, with a minimum of 5 uroflow studies in all patients. PEBC and PVR were correlated with age and type of initial treatment, with p 10% did not change when initial and last FU were compared (p=0.29). Overall, 8/39 (21%) are on CIC and 21/31 (68%) are double voiding. CONCLUSIONS: PEBC in PUV increases gradually over time, with larger than expected bladder volumes detected in 90% of boys after age 11. Despite this,75% of pts manage to empty their bladders by CIC and double voiding. Our data suggests that detrusor decompensation appears to ultimately occur in most PUV pts despite the fact that some were diverted early in life. Source of Funding: None