Early urodynamic findings after complete primary repair of exstrophy.

INTRODUCTION: Detrusor contraction in bladder exstrophy (BE) patients following reconstruction is poorly understood as there are few published studies assessing urodynamic findings in this population. Understanding the ability of the detrusor to contract in BE patients early after closure may be able to inform the longer-term management and potential for the development of future continence in this population. OBJECTIVE: We sought to evaluate early detrusor contraction using urodynamic studies (UDS) in children who had previously undergone complete primary repair of bladder exstrophy (CPRE). We hypothesized that a majority of children with BE would display the presence of normal detrusor contractile function after CPRE. STUDY DESIGN: A retrospective review of our prospectively collected database was performed for all patients with a diagnosis of classic BE who underwent primary CPRE between 2013 and 2017. From this cohort we identified patients with at least one post-operative UDS at 3 years of age or older who had undergone an initial CPRE. Our primary outcome was the presence of a detrusor contraction demonstrated on UDS. RESULTS: There were 50 children (31 male, 19 female) with CBE who underwent CPRE between 2013 and 2017.There were 26 (13 male, 13 female) who met inclusion criteria. Median age was 3.5 (IQR: 3.2-4.7) years at the time of UDS Sixteen of the 26 (61.5%) generated a sustained detrusor contraction generating a void, with a median peak voiding pressure of 38 cm H20 (IQR: 28-51). The median bladder capacity reached was 48 ml, which represented a median of 30% of expected bladder capacity. The median post void residual (PVR) for the entire cohort was 26 ml (IQR: 9, 47) or 51% (IQR: 20%-98%) of their actual bladder capacity, while the median PVR for those children with a sustained detrusor contraction was 18 ml (IQR: 5, 46) or 33% (IQR: 27%, 98%) of their actual bladder capacity. Intraoperative bladder width and bladder dome to bladder neck length did not correlate with the presence of voiding via a detrusor contraction (p = 0.64). DISCUSSION: We present the first study assessing early UDS finding of detrusor contraction in BE patients after CPRE. In our cohort, 61.5% of patients were able to generate a sustained detrusor contraction on UDS which is a higher percentage than has been reported in previous series. A difference in initial surgical management may account for these findings. CONCLUSION: At short term follow up, the majority of children in our cohort were able to produce sustained detrusor contractions sufficient to generate a void per urethra with a modest post void residual volume. Long-term follow-up and repeated UDS will be needed to track detrusor contractility rates, bladder capacities, compliance, post void residuals and ultimately continence rates over time.

A single-institution experience of complete primary repair of bladder exstrophy in girls: risk factors for urinary retention.

INTRODUCTION: Historically after complete primary repair of exstrophy (CPRE) in girls, it had been more likely to observe urinary incontinence than retention. Following recent technical modifications of elongating the urethra and narrowing the bladder neck, the authors have observed a high rate of urinary retention in girls after CPRE. OBJECTIVE: The aim was to identify factors that may be responsible for this observation by reviewing historical and current outcomes. The authors hypothesized that differences in anatomic dimensions at the time of CPRE may contribute to urinary retention. STUDY DESIGN: A retrospective review of girls who underwent CPRE from December 1998 through September 2016 from a single institution was performed. Patients were deemed in retention if their clinical course was consistent with such, required a procedure to relieve urinary retention, and/or required clean intermittent catheterization. RESULTS: Nineteen girls underwent CPRE during this period. In 2012, a change to delaying CPRE to approximately 2 months of age was made, and this led the authors to divide their experience into CPRE performed as a newborn (<72 h of age, 8 patients) versus delayed (>72 h, 11 patients) subgroups. There were no girls with retention in the newborn group and three (38%) girls with retention in the delayed group. In the delayed group, girls had a longer urethral plate and narrower bladder neck compared with the newborn group. Long-term outcomes greater than 9 years are available for six girls in the newborn group and two (33%) required bladder neck procedures for incontinence. None in the delayed group have required incontinence procedures; however, follow-up is limited at 25 months. DISCUSSION: The absence of retention in the newborn group is concerning for the delayed group incurring a higher risk of retention after CPRE. This may be secondary to excessive compression of the urethra at the time of pubic symphysis approximation potentially leading to urethral ischemia. Different from the newborn CPRE girls, additional technical revision of CPRE, namely, elongation of the urethra and the dissection it involves and narrowing of the bladder neck, may increase the risk for retention. CONCLUSIONS: The multiple factors that were identified as potential contributors to post-CPRE urinary retention should result in a cautious reevaluation of female bladder exstrophy management at the time of CPRE. The authors now create a gradual tapered transition at the bladder neck and, similar to their previous experience, a more generous (wider) bladder neck and a shorter length for urethral plate.

Anatomic findings associated with epispadias in boys: Implications for surgical management and urinary continence.

INTRODUCTION: Pre-operative physical examination of male epispadias allows for classification of epispadias level as glanular (GE), penile (PE) or penopubic (PPE), and for delineation of anatomic anomalies. The incidence of associated extragenital abnormalities, such as vesicoureteral reflux (VUR), bladder neck (BN) abnormality and abnormal pubic diastasis (PD), and their impact on urinary continence has not yet been systematically studied. OBJECTIVE: The goal of this study was to evaluate whether the more proximal level of epispadias correlated with associated extragenital anatomic anomalies seen on initial imaging or endoscopic evaluation, and whether these pre-operative findings contributed to subsequent surgical management and impacted on achieving urinary continence. It was hypothesized that the more severe forms of epispadias may be associated with a higher frequency of associated anomalies. STUDY DESIGN: The study was an IRB-approved, retrospective case study of all male patients treated initially for isolated epispadias at the current institution between 1994 and 2011. Data collection was achieved by chart and radiology review evaluating PD, BN appearance, presence of VUR, surgical treatment, and urinary continence. RESULTS: A total of 26 patients were identified and divided into three groups based on appearance at physical examination: four glanular (GE), eight penile (PE), and 14 penopubic (PPE); 17 patients had an abnormal BN. Reflux was noted in nine of 20 patients who had a voiding cystourethrogram (VCUG), two of which had an episode of pyelonephritis. Of the 22 patients past the age of toilet training, 17 were continent (64% (9/14) penopubic, 63% (5/8) penile, and 75% (3/4) glanular). DISCUSSION: Anatomic classification for male epispadias did not provide sufficient information regarding extragenital findings. This study provided new information regarding PD, BN appearance, presence of reflux, and ultimate urinary continence. Pubic diastasis and BN abnormalities were more frequently seen in more severe forms of epispadias, whereas VUR seemed more prevalent in less severe forms. A template for pre-operative evaluation was outlined. Limitations of the study were its retrospective design and relatively small cohort of patients, which reflected the rarity of the condition. CONCLUSION: Based on the information generated, additional anatomic information was generated regarding boys with epispadias. This information will help guide the evaluation and the management of these patients in the future.

Short-term outcomes of the multi-institutional bladder exstrophy consortium: Successes and complications in the first two years of collaboration.

INTRODUCTION/BACKGROUND: Bladder exstrophy is a rare diagnosis that presents major reconstructive challenges. To increase experience and proficiency in the care of bladder exstrophy (BE), the Multi-Institutional BE Consortium (MIBEC) was formed, with a focus on refining technical aspects of complete primary repair of bladder exstrophy (CPRE) and subsequent care. OBJECTIVE: Outcome measures included successful CPRE (absence of dehiscence), complications, and integrated points of technique and care over the short-term. STUDY DESIGN: Boston Children's Hospital, Children's Hospital of Philadelphia and Children's Hospital of Wisconsin alternately served as the host, with observation, commentary and critique by visiting collaborating surgeons. CPRE with bilateral iliac osteotomy was performed at 1-3 months of age. High-definition video capture of the surgery allowed local and distant broadcast to facilitate real-time observation and teaching, and recording of all procedures. RESULTS: From February 2013 to February 2015, MIBEC participating surgeons performed CPRE on 27 consecutive patients (22 classic BE, five epispadias). There were no dehiscences in 27 patients (0%, 95% CI 0-12.5%). Thirteen girls and 14 boys underwent CPRE at a median age of 2.3 months (range 0.1-51.6). One boy had a hypospadiac urethral meatus at CPRE completion. Hydronephrosis of mild or moderate grade was present postoperatively in eight girls and two boys. Additional results, per gender, are presented in the Summary table below. DISCUSSION: Absence of dehiscence in this cohort was comparable or compared favorably with the literature. However, several girls had significant obstructive complications following CPRE. The rate of bladder outlet obstruction (BOO) in girls was increased compared with published reports. A low complication rate was noted in the boys following CPRE, which was comparable to reports in the literature, and early signs of continence and spontaneous voiding were noted in some boys and girls. Limitations included variation in patient age at presentation, thereby introducing a wide age range at CPRE. Outcome data were limited by short follow-up regarding voiding with continence. CONCLUSION: This collaborative effort proved beneficial regarding significantly increased surgeon exposure to CPRE, refinement of CPRE technique, surgeon learning and expertise. Technical refinement of CPRE is ongoing.

Sacral agenesis and neurogenic bladder: Long-term outcomes of bladder and kidney function.

BACKGROUND: Sacral agenesis (SA) is a rare congenital condition that refers to the absence of part or all of two or more lower sacral vertebral bodies. It can be associated with neurogenic bladder dysfunction that does not necessarily correlate with the level of spinal or skeletal defect. Patients with SA should undergo urodynamic studies (UDS) to guide lower urinary tract (LUT) management. OBJECTIVE: This review aimed to update the present institutional experience since 1981 of this rare patient population with detailed, long-term follow-up of bladder and kidney function. STUDY DESIGN: A single institution, retrospective, IRB-approved review was performed on patients born after January 1, 1981 with an isolated diagnosis of sacral agenesis without spina bifida, and followed with urologic involvement at Boston Children's Hospital. Records were reviewed for demographics, radiologic imaging, UDS including cystometrogram (CMG) and electromyography (EMG), surgery, and blood chemistries. Comparisons were made between groups of patients based on age at diagnosis, with specific focus on renal function and stability of neurogenic bladder lesion. RESULTS: Forty-three patients were identified: 23 female and 20 male. Thirty-seven children (86%) had a known age of diagnosis. Nineteen were diagnosed before 2 months old, including five who were diagnosed prenatally, 11 were diagnosed between 2 and 18 months, and seven were diagnosed after 18 months. All 43 had UDS, with 24 (55.8%) studied at the time of diagnosis (Summary Table). Twenty had serial full UDS, with 30% demonstrating neurourologic instability. None developed end-stage renal disease (ESRD) or required spinal cord detethering. DISCUSSION: Many children with SA appeared to be diagnosed prenatally or early in life; SA was mostly identified during evaluation of associated anomalies. Though UDS aid in urologic management, testing was not routinely utilized at the time of diagnosis. CONCLUSIONS: This review of long-term follow-up in SA patients showed stable LUT and renal function, with minimal risk of progression to ESRD.

Renal biopsy in congenital ureteropelvic junction obstruction: evidence for parenchymal maldevelopment.

The renal histologic changes associated with congenital ureteropelvic junction obstruction (UPJO) and the relationship to clinical imaging have not been well studied. In order to better understand the histologic alterations of congenital UPJO and their relationship with clinical imaging and outcomes, we examined renal biopsies from 61 patients undergoing pyeloplasty for congenital UPJO. Glomeruli were analyzed for various injury patterns and the tubulointerstitium was examined for tubular atrophy/simplification and fibrosis. Two methods were used to evaluate tubular mass: glomerular density and morphometric measurement of tubular size and density. Control specimens were obtained from age-matched autopsy specimens without renal pathology. Glomerular changes were identified in 73% of all biopsies and were present in a range from 1.7 to 91% of glomeruli in each patient. Overt tubulointerstitial changes were present in 26% of all biopsies. Fibrosis was noted to occur with tubulointerstitial changes in a significantly greater fraction of children over the age of 1 year (P=0.026). Increased glomerular density was associated with severe hydronephrosis (P<0.02). Normal glomerular density was inversely correlated with age (P<0.001), but this relationship was more variable in UPJO (P<0.01). Among patients with intact differential function preoperatively (>45%), postoperative functional decline was predicted only by increased glomerular density. 20 biopsies without overt tubulointerstitial changes were analyzed morphometrically and showed a significant reduction in proximal tubular (PT) size, but unchanged density. Distal tubular (DT) size was unchanged in UPJO, but density was increased. The PT/DT ratio was therefore markedly decreased in UPJO (P<0.0001). Both PT and DT sizes were significantly larger in children with a diuretic renogram washout time less than 20 min than those with greater than 20 min, a common threshold for functionally significant obstruction (P<0.05). Capsular thickness was significantly increased in UPJO. In all, 36% of biopsies had a thickness >0.5 mm and this was associated with greater degrees of tubulointerstitial changes and glomerular alterations. Congenital UPJO produces a variety of renal parenchymal changes, which may in part reflect abnormal development. Some of these alternations are seen in clinical imaging and may help predict outcomes, but there is significant discordance between conventional imaging and histological findings.

Neonatal scrotal haematoma: mimicker of neonatal testicular torsion.

OBJECTIVE: To describe the clinical features of neonatal scrotal haematoma and distinguish them from those of neonatal testicular torsion. PATIENTS AND METHODS: Five neonates presenting with an acute scrotum and initial diagnosis of neonatal testicular torsion were found to have neonatal scrotal haematoma. In one case the diagnosis was surgical and in four subsequent cases the diagnosis was by colour Doppler ultrasonography, and surgery was avoided. Four of the five children had risk factors associated with neonatal scrotal haematoma, including bleeding diathesis, birth trauma and high birth weight. CONCLUSIONS: The importance of including haematoma in the differential diagnosis of the acute neonatal scrotum is emphasized, as is the value of contemporary Doppler ultrasonography in making this diagnosis.

The outcome of voiding dysfunction managed with clean intermittent catheterization in neurologically and anatomically normal children.

OBJECTIVE: To describe the tolerability and efficacy of clean intermittent catheterization (CIC) in the management of dysfunctional voiding in patients who are neurologically and anatomically normal. PATIENTS AND METHODS: The medical records were reviewed in 23 patients (16 girls, mean age 9 years, range 6-14.5, and seven males, mean age 8 years, range 5-20.5) with urinary incontinence and/or urinary tract infection (UTI) who were offered CIC because they had a large postvoid residual urine volume (PVR). All had extensive instruction before starting CIC. All patients underwent urodynamic studies, and urinary and fecal elimination habits were recorded. Detrusor hyperactivity, when present, was treated with anticholinergic medication. The follow-up evaluation included tolerance of CIC, continence status and the incidence of UTI. Behavioural modification or biofeedback training was not used in any patient. RESULTS: Of the 23 patients, 13 presented with both UTI and urinary incontinence, five with incontinence only, four with UTI only, one with frequency and no incontinence, and one with haematuria. Associated symptoms included frequency/urgency, constipation or soiling, and straining to void or incomplete emptying (in nine each), and infrequent voiding in six. CIC was performed within 2 days by 15 patients, while four others required up to 2 weeks to master CIC. However, three of the four patients (all older girls) who needed 2 weeks to learn the technique did not tolerate CIC and discontinued it within 3 weeks. Four other adolescents (three girls and one boy) refused to learn CIC. Of the 16 patients remaining on CIC only three had cystitis; no patient had a febrile UTI. Once successfully instituted, all patients became continent while on CIC. Six boys (mean follow-up 4 months) had a marked decrease in their PVR. CIC was discontinued in three girls who voided normally to emptiness within 6 months of starting CIC; they remained dry and infection-free 16 months (two) and 6 years later. CONCLUSION: CIC is a viable therapeutic option for the treatment of dysfunctional voiding, associated with a large PVR, in the absence of any neurological abnormality. CIC is well tolerated in the sensate patient and provides a means for expeditiously achieving continence and improving bladder emptying cost-effectively.

Tubularized incised plate urethroplasty: expanded use in primary and repeat surgery for hypospadias.

PURPOSE: We evaluated the impact of tubularized incised plate urethroplasty on primary and repeat hypospadias repair. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all boys who underwent hypospadias repair at our institution during a recent 3-year period. The level of the hypospadias defect, technique of repair, primary repair versus reoperation, age at surgery and complications were recorded. RESULTS: A total of 520 hypospadias repairs were done from May 1996 through June 1999. We began to perform tubularized incised plate urethroplasty in November 1996. During the ensuing consecutive 32 months 181 primary and 25 repeat hypospadias repairs were done using this technique. Mean patient age at surgery was 22 months (range 3 months to 30 years). During the 6 months immediately before we began to use this method the Mathieu flip-flap procedure was the most commonly performed technique, accounting for 38% of all hypospadias repairs. In contrast, during the last 6 months reviewed tubularized incised plate urethroplasty accounted for 63% of all repairs, including 41 of 65 primary operations (63%) and 4 of 6 reoperations (67%), while no Mathieu procedures were performed. Postoperative followup was 6 to 38 months for tubularized incised plate repair. Overall meatal stenosis and a urethrocutaneous fistula developed in 1 and 14 boys, respectively (7% complication rate). CONCLUSIONS: Tubularized incised plate urethroplasty has become the preferred technique of primary and repeat hypospadias repair at our institution. The technique has few complications as well as proved success and versatility that continues to expand its applicability and popularity.

99m Technetium dimercapto-succinic acid renal scintigraphy abnormalities in infants with sterile high grade vesicoureteral reflux.

PURPOSE: Although vesicoureteral reflux associated with bacteriuria may cause renal scarring, sterile reflux is thought not to cause renal injury. We determined the incidence and associated characteristics of renal abnormalities using 99mtechnetium(Tc) dimercapto-succinic acid (DMSA) renal scintigraphy in infants with high grade vesicoureteral reflux but no history of urinary tract infection. MATERIALS AND METHODS: We retrospectively reviewed the results of 99mTc-DMSA renal scintigraphy and renal ultrasonography performed during the first 6 months of life in infants with vesicoureteral reflux detected during the postnatal evaluation of prenatal hydronephrosis or sibling reflux screening. Those with a history of urinary tract infection, or evidence of ureteropelvic junction or bladder outlet obstruction were excluded from study. RESULTS: Of the 28 male and 6 female infants who met study criteria vesicoureteral reflux was bilateral in 25 and unilateral in 9. Reflux grade was IV or V, II or III and I in 38, 18 and 3 of the 59 refluxing renal units, respectively. 99mTc-DMSA renal scintigraphy revealed parenchymal abnormalities in 24 refluxing renal units (41%) in 22 patients (65%), of whom 19 (86%) were male and 15 (68%) had bilateral reflux. We noted differential uptake less than 40% with and without cortical defects in 10 and 7 refluxing units, respectively, and cortical defects only in 7. Of the 24 refluxing units with abnormalities 21 were associated with grade IV or V and 3 with grade II or III reflux. Ultrasound showed evidence of renal injury in only 7 of the 17 patients (41%) in whom 99mTc-DMSA scintigraphy was abnormal. CONCLUSIONS: In our study the majority of infants with high grade reflux had decreased differential function and/or cortical defects. Parenchymal defects detected by 99mTc-DMSA renal scintigraphy were often not identified by renal ultrasound. Therefore, 99mTc-DMSA renal scintigraphy is especially useful for initially evaluating infants with high grade, sterile vesicoureteral reflux.

The spectrum of Sertoli cell tumors in children.

The spectrum of Sertoli cell tumors in children covers a wide range of testis and ovarian tumors classified as sex cord-stromal tumors. Sertoli cell tumor of the testis is extremely rare in the pediatric population. The American Academy of Pediatrics Section on Urology Prepubertal Testicular Tumor Registry has reported a total of six cases of Sertoli cell tumor of the testis, accounting for 1.3% of the 430 cases reported to the registry as of October 1996. Despite their rarity, Sertoli cell variants of sex cord-stromal tumors have generated keen interest because of their variable histologic appearance and biologic behavior, including endocrine activity. Because sex cord-stromal tumors occur in the ovary and testis, a primitive cellular origin to these tumors is likely in males and females.

Pediatric retroperitoneoscopic nephrectomy.

The endoscopic retroperitoneal (retroperitoneoscopic) approach to extirpative intervention for benign renal disease is increasingly popular. We describe several modifications of this approach, including the use of prone positioning and 2-mm instruments, that may improve the safety and efficacy of the technique in children. These modifications provide unobstructed views of the kidney and renal hilum and facilitate dissection in a small working space.

Ketorolac suppresses postoperative bladder spasms after pediatric ureteral reimplantation.

UNLABELLED: We evaluated the efficacy of ketorolac in suppressing postoperative bladder spasms after ureteroneocystostomy (ureteral reimplantation). Twenty-four pediatric patients undergoing intravesical ureteroneocystostomy were enrolled prospectively to receive either ketorolac or placebo via double-blinded randomization. Twelve patients in each group shared similar preoperative characteristics. All were maintained on an epidural infusion of bupivacaine (0.1%) with fentanyl (2 microg/mL) throughout the study. Patients were given either ketorolac (0.5 mg. kg(-1). dose(-1)) or placebo (equivalent volume saline) IV after surgery and every 6 h thereafter for 48 h. Parents were instructed to record bladder spasm episodes prospectively by using a standardized time-flow diary. Three patients (25%) in the ketorolac group experienced bladder spasms, compared with 10 patients (83%) in the placebo group (two-sided P < 0.05). The median severity score for the ketorolac group was 1.2 (mild = 1.0, severe = 3.0), compared with 2.6 for the placebo group (P = 0.003). We conclude that IV ketorolac reduces the frequency and severity of postoperative bladder spasms after intravesical ureteroneocystostomy. IMPLICATIONS: We studied the efficacy of ketorolac, a prostaglandin synthesis inhibitor, in the treatment of bladder spasm after ureteroneocystostomy (antireflux operation). Patients were randomized in a double-blinded manner to receive either ketorolac or placebo after the surgery. We demonstrate that ketorolac reduces the frequency and severity of postoperative bladder spasm.

Amphiregulin is coordinately expressed with heparin-binding epidermal growth factor-like growth factor in the interstitial smooth muscle of the human prostate.

Peptide growth factors have been proposed as mediators of smooth muscle-epithelial cell interactions in the human prostate; however, the identity of these molecules has not been established. In this study, we compared expression levels of messenger RNAs (mRNAs) encoding the epidermal growth factor (EGF) receptor-related receptor tyrosine kinases (ErbB1 through 4), the six EGF receptor ligands, EGF, transforming growth factor (TGF)-alpha, amphiregulin (ARG), HB-EGF, betacellulin, and epiregulin, and the related molecule heregulin-alpha, in a series of 10 prostate tissue specimens. Only EGF showed a disease-specific association, with increased mRNA levels in four of five PCa specimens in comparison to matched normal tissue from the same subject. In contrast, ARG and HB-EGF mRNAs showed a coordinate pattern of expression in 7/10 specimens that was distinct from all other growth factor or receptor genes examined and from mRNAs for prostate specific antigen, the androgen receptor and GAPDH, a house-keeping enzyme. Analysis of an additional series of benign prostatic hyperplasia and prostate cancer specimens from 60 individuals confirmed that ARG and HB-EGF mRNA levels varied in a highly coordinate manner (r = 0.93; P < 0.0001) but showed no association with disease. ARG was immunolocalized largely to interstitial smooth muscle cells (SMC), previously identified as the site of synthesis of HB-EGF in the prostate, while the cognate ARG and HB-EGF receptor, ErbB1, was localized exclusively to ductal epithelial cells and carcinoma cells. Although ARG was a relatively poor mitogen for Balb/c3T3 cells in comparison to HB-EGF, it was similar in potency to HB-EGF in stimulating human prostate epithelial cell growth, suggesting that prostate epithelia may be a physiologic target for ARG in vivo. Expression of both ARG and HB-EGF mRNAs was induced in cultured prostate SMC by fibroblast growth factor-2, a human prostate SMC mitogen linked to prostate disease. These findings indicate that ARG and HB-EGF are likely to be key mediators of directional signaling between SMC and epithelial cells in the human prostate and appear to be coordinately regulated.

Heparin-binding EGF-like growth factor expression increases selectively in bladder smooth muscle in response to lower urinary tract obstruction.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF), an activating ligand for the epidermal growth factor receptor (ErbB1) tyrosine kinase and at least one isoform of the ErbB4 receptor tyrosine kinase, is synthesized by the smooth muscle of the human bladder wall. In this study we tested the hypothesis that HB-EGF plays a role in the bladder-wall thickening that occurs in response to obstructive syndromes affecting the lower urinary tract, possibly by acting as an autocrine smooth muscle cell (SMC) growth factor. HB-EGF was mitogenic for primary culture human bladder SMC, and cell growth in serum-containing medium was inhibited more than 70% by [Glu52]-diphtheria toxin/CRM197, a specific HB-EGF inhibitor, consistent with a physiologic role for HB-EGF as an autocrine bladder SMC mitogen. Human and mouse bladder SMC in vivo and cultured human bladder SMC expressed the primary HB-EGF receptor, ErbB1, but not mRNA for the secondary HB-EGF receptor, ErbB4, thereby identifying ErbB1 as the cognate HB-EGF receptor in the bladder wall. Reverse transcription-polymerase chain reaction analysis also demonstrated ErbB2 and ErbB3 expression in human bladder muscle tissue, suggesting the possibility of receptor cross-talk after ErbB1 activation. Urethral ligation in mice resulted in an increase in steady-state HB-EGF mRNA expression up to 24 hours in whole bladder tissue in comparison with ErbB1 and glyceraldehyde 3-phosphate dehydrogenase mRNA levels, which did not change in a demonstrable pattern. HB-EGF protein increased coordinately with HB-EGF mRNA levels. Dissection of bladder tissue into muscle and mucosal layers demonstrated that the increase in HB-EGF mRNA occurred predominantly in the muscle layer, with peak levels (13-fold higher than sham controls) occurring 12 hours after obstruction. These data support a physiologic role for HB-EGF as a mediator of hypertrophic bladder tissue growth.

Pediatric retroperitoneoscopic nephrectomy using 2 mm. instrumentation.

PURPOSE: We describe several modifications of the retroperitoneoscopic approach to nephrectomy for benign renal disease, including the use of 2 mm. instrumentation and prone patient positioning. MATERIALS AND METHODS: A total of 14 children underwent retroperitoneoscopic nephrectomy in the prone position. An inflatable dissecting device was inserted into the retroperitoneum after a small muscle splitting incision was made at the lateral border of the sacrospinalis muscle approximately 1 cm. below the costovertebral angle. After inflation the dissecting device was replaced with a 5 mm. cannula and pneumoretroperitoneum was maintained with carbon dioxide insufflation. Two 2 mm. trocars were then placed under endoscopic guidance. Dissection was performed using 2 mm. instrumentation and the specimen was retrieved through the largest port site. RESULTS: Nephrectomy was performed in 9 girls and 5 boys 3 months to 9.8 years old. The preoperative diagnosis included chronic pyelonephritis with minimal renal function, reflux with a nonfunctioning kidney, multicystic dysplastic kidney, an upper pole dysplastic moiety with an associated ureterocele and a dysplastic kidney with a vaginal ectopic ureter. Mean operative time for retroperitoneoscopic nephrectomy was 142 minutes with an estimated blood loss of less than 15 ml. Contralateral ureteral reimplantation was performed after retroperitoneoscopic dissection in 5 patients. Overall average hospital stay was 2 days and there were no complications. CONCLUSIONS: Several modifications of the retroperitoneal approach, including the use of prone patient positioning and 2 mm. instrumentation for visualization and dissection, may improve the safety and efficacy of this technique in children.

Current trends in hypospadias repair.

There is no single, universally applicable technique for hypospadias repair. Command of a technically straightforward repair with few complications and proven success and versatility in a reasonable range of hypospadias defects are desired goals. Several well-established techniques exist for the repair of all hypospadias defects. The Snodgrass tubularized incised plate urethroplasty, a recent contribution with exemplary early results, has become a popular technique for primary and preoperative repair of middle and anterior hypospadias. Other innovative modifications, and technical advances, such as the use of laser and tissue solder, continue to emerge. With time, these may herald improvements to even the most basic of sound principles involved in all hypospadias repair.

Renal findings on radiological followup of patients with Beckwith-Wiedemann syndrome.

PURPOSE: The Beckwith-Wiedemann syndrome is most commonly characterized by macroglossia and abdominal wall defect(s), and it carries a predisposition to embryonal tumors, including Wilms tumor. We report our experience with the character and incidence of renal disease in patients with the Beckwith-Wiedemann syndrome, and discuss the role of radiological followup. MATERIALS AND METHODS: We reviewed the medical records of all patients diagnosed with the Beckwith-Wiedemann syndrome who were treated at our institution between March 1979 and February 1998. Radiological followup consisted of renal ultrasound at approximately 3 to 6-month intervals with the addition of computerized tomography or magnetic resonance imaging (MRI) in patients with an indeterminate lesion(s) or nephrogenic rest(s). RESULTS: A total of 29 patients were identified. Of these cases renal ultrasound showed normal kidneys bilaterally in 19 (70%), simple cysts in 5 (19%), indeterminate lesion(s) in 2 (7%) and nephrocalcinosis in 1 (4%). Nephrogenic rests were followed with MRI in 1 patient, and 1 in whom a 2 cm. mass was revealed by followup MRI underwent partial nephrectomy and chemotherapy for stage I Wilms tumor. CONCLUSIONS: The 3.7% incidence of Wilms tumor in our patients with the Beckwith-Wiedemann syndrome is similar to that in previously published reports. Aggressive follow-up by a sensitive radiological technique is warranted in cases of the Beckwith-Wiedemann syndrome, and associated hemihypertrophy and/or nephromegaly with or without evidence of a Wilms tumor precursor. The detection of suspected malignant disease at an early stage may permit curative nephron sparing surgery.

Stretch activates heparin-binding EGF-like growth factor expression in bladder smooth muscle cells.

Cultured rat bladder smooth muscle cells (SMC) were grown on collagen-coated silicone membranes and subjected to continuous cycles of stretch-relaxation. Semiquantitative RT-PCR analysis revealed a time-dependent increase in heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) mRNA levels after stretch, with maximal levels appearing after 4 h. Immunostaining for proHB-EGF revealed higher levels of HB-EGF protein in the stretched than in the nonstretched SMC. The ANG II receptor type 1 antagonist losartan markedly suppressed stretch-activated HB-EGF expression. ANG II levels were 3.3-fold higher in the stretch- than in the non-stretch-conditioned media. Stretch stimulation of bladder SMC that had been transiently transfected with an HB-EGF promoter-luciferase expression construct resulted in an 11-fold increase in reporter activity. Mechanical stretch induced a 4.7-fold increase in tritiated thymidine incorporation rate, and this was reduced by 25% in the presence of losartan. We conclude that mechanical stretch activates HB-EGF gene expression in bladder SMC and that this is mediated in part by autocrine ANG II secretion.

Large-cell calcifying Sertoli cell tumor of the testis: case report and review of the literature.

Large-cell calcifying Sertoli cell tumor (LCCSCT) is a rare sex cord-stromal tumor found predominantly in the pediatric population. This tumor has distinctive histopathologic features and clinical associations. LCCSCT has also been noted in association with the Carney complex, and in patients with Peutz-Jeghers syndrome. The propensity to metastasize is low, and radical orchiectomy has traditionally been the treatment of choice.