Complete primary repair of bladder exstrophy is associated with detrusor underactivity type of neurogenic bladder.

OBJECTIVE: To test the hypothesis that complete primary repair of bladder exstrophy (CPRE) is associated with detrussor underactivity. For this purpose, we review (1) our experience, (2) the results of the published literature as it pertains to bladder function, and (3) the known anatomic basis on which the mechanism of the observed outcome can be understood. METHODS: The medical records of all patients who underwent CPRE by the author between 2004 and 2010 were reviewed. Attention was focused on the clinical, imaging, and urodynamic findings. RESULTS: Four men and 2 women underwent CPRE. Follow-up ranges from 2 to 8 years. Four underwent bilateral ureteral reimplantation combined with bladder neck repair in 3. Detrusor activity (or overactivity) was not recorded in the 5 patients who underwent urodynamic studies. Four patients achieved short periods of urinary continence. The percent predicted bladder capacity, adjusted for age, ranged from 25 to 70, with a median of 60. Of the 68 publications on CPRE since 1999, none reports the presence of detrusor activity. A description of the pelvic plexus anatomy by Walsh and Donker provides a basis for the mechanism of injury resulting in the previously mentioned results: (1) complete penile disassembly eliminates the distal fixation point of the bladder-urethral plate, (2) the subsequent dissection and mobilization result in shearing injury to the microscopic pelvic plexus branches to the bladder, external sphincter, and prostatic urethra. CONCLUSION: CPRE results in disruption of the branches of the pelvic plexus and a neurogenic bladder (detrussor underactivity).

Urinary proteome analysis in patients with stable SFU grade 4 ureteropelvic junction obstruction differs from normal.

OBJECTIVE: To evaluate and analyze the urinary proteome in infants with stable grade 4 ureteropelvic junction obstruction (UPJO) and compare to age-matched normal controls. METHODS: Bladder urine specimens were obtained from 21 healthy infants with normal maternal/fetal ultrasound and 25 infants with grade 4 unilateral UPJO. All patients had >40% ipsilateral individual kidney function by renal scanning and the anteroposterior (AP) diameter of the hydronephrotic kidney ranged from 1.6-3.9 cms at presentation. Over a 5-year follow-up period, the disease progressed in 7 infants (28%), resolved in 4 (16%), and remains stable in the majority (56%). The urinary specimens were prepared using standard methods and subjected to LC/MS/MS analysis. The normalized data were annotated utilizing the Ingenuity Pathways Analysis (IPA; www.Ingenuity.com) knowledge platform. RESULTS: In the stable UPJO group, the urinary proteomes obtained in infancy differed significantly from the age-matched controls. Analysis revealed important differences in a number of biologic functions including inflammation, apoptosis, tubular injury and fibrosis, and reactive oxygen species response. CONCLUSION: The urinary proteomes from the bladder in patients with stable grade 4 UPJO (by imaging criteria) are significantly different at birth and during the first year of life and seem to indicate the presence of an ongoing active renal response to UPJO. The imminent discovery of surrogate urinary biomarkers may result in reconsideration of the watchful waiting strategy during this critical period of renal maturation and development in infancy.

Hydronephrosis: a view from the inside.

Unilateral ureteropelvic junction obstruction (UPJO) is the most common prenatally detected disease leading to hydronephrosis. The obstructive anatomic lesion leads to varying degrees of hydronephrosis, ranging from no apparent effect on renal function to atrophy. Furthermore, the natural course of hydronephrosis varies from spontaneous resolution to progressive deterioration and may take upwards of 3 years for a kidney to declare itself. The objectives of this article are to update our knowledge regarding the evaluation and management of UPJO in depth and to discuss the emerging value of urinary proteome analysis to the clinical arena.

Surgical technique for antegrade dissection of the preputial vascular pedicle during hypospadias repair.

OBJECTIVE: Both layers of the prepuce can be used as vascularized flaps in hypospadias repair. The aim of this communication is to describe an antegrade approach to the harvesting of the vascular pedicle. SURGICAL TECHNIQUE: The vascular pedicle is isolated at the level of the penopubic junction where it is most robust. Dissection then proceeds distally towards the prepuce fanning laterally. RESULTS: Of 306 boys presenting for hypospadias repair in 2002-2008, this approach was utilized in 235 (77%). The vascularized flap was used as 1) a classic single or double faced onlay flap in 95, 2) a vascularized layer to cover a tubularized incised plate urethroplasty in 68, 3) a tube-onlay in 39, 4) a tubularized urethroplasty in 23, 5) for ventral skin coverage alone in 7, and 6) for a planned first stage repair in 3. Age at repair averaged 12 months (range 2-160) and follow up 36 months (range 2-68). CONCLUSIONS: Antegrade dissection of the vascular pedicle is a simple, expeditious and reliable way of isolating the prepuce on its blood supply. The versatility of the resulting flaps allows the repair to be adapted to the individual anatomic conditions as opposed to one type of repair being used for all variants.

Candidate urinary biomarker discovery in ureteropelvic junction obstruction: a proteomic approach.

PURPOSE: Ureteropelvic junction obstruction may either worsen and require surgery, improve or remain stable. It may take upward of 3 years for the natural history to unfold. Urinary proteome analysis using capillary electrophoresis mass spectrometry has been shown to differentiate between normal infants and those with ureteropelvic junction obstruction. We sought to confirm these findings using liquid chromatography/nano-spray mass spectrometry to examine the urinary proteome in patients with unilateral grade IV ureteropelvic junction obstruction compared to age matched healthy infants. MATERIALS AND METHODS: Urine specimens were obtained from 21 healthy infants with normal maternal/fetal ultrasound and 25 infants with grade IV unilateral ureteropelvic junction obstruction. Specimens were prepared using standard methods and subjected to liquid chromatography/tandem mass spectrometry analysis. Normalized data were annotated using the IPA(R) knowledge platform. RESULTS: There were 31 proteins significantly different in their level of abundance at 1 to 6 months, and 18 at 7 to 12 months compared to age matched controls. These proteins clustered into major functional networks. All of the biomarkers previously reported in clinical studies of ureteropelvic junction obstruction were observed with the notable exception of transforming growth factor-beta1. CONCLUSIONS: These results confirm the presence of significant differences in the urinary proteome in unilateral ureteropelvic junction obstruction compared to age matched normal individuals. This study adds new information about levels of abundance of specific proteins and peptides in ureteropelvic junction obstruction, which may allow for better classification of disease subgroups and help to establish improved indications for the early selection of surgical candidates based on urinary protein biomarkers.

Urinary proteome analysis and the management of ureteropelvic junction obstruction.

Ureteropelvic junction obstruction (UPJO) detected prenatally may over time deteriorate and require surgery, improve, or remain stable, and it may take upwards of 3 years for its natural history to unfold. Clinical decisions for or against operative corrections are usually based on scintigraphy follow-up studies. A non-invasive method for facilitating clinical decisions has recently been presented: urinary proteome analysis utilizing capillary electrophoresis mass spectrometry (CE-MS) has been shown to predict the outcome of UPJO in newborns. The group that developed this assay has now validated their seminal findings and extended the investigations to older age groups (this issue). The results of the blinded analysis correctly identified patients with UPJO who underwent surgery with a sensitivity of 83% (5 of 6 patients) and a specificity of 92% (12 of 13 patients) in infants up to 1 year of age. The validity of the analysis was poor in children >1 year of age with unilateral UPJO. A large number of patients will be needed to answer the question of to what extent the normal variability of urinary proteomes overlap with the variability of the pattern in UPJO beyond early infancy.

Bypass pyeloplasty: description of a procedure and initial results.

INTRODUCTION AND OBJECTIVE: Dismembered pyeloplasty is the surgical technique of choice for open, laparoscopic and/or robot-assisted repair of ureteropelvic junction obstruction (UPJO). We describe a new technique, bypass pyeloplasty, ideally suited for the high inserting ureter, and present initial results. PATIENTS AND METHODS: A wide 1-2-cm side-to-side anastomosis is created between the dilated and elastic portion of the ureter just distal to the UPJO and the lower and dependent portion of the hydronephrotic renal pelvis. The UPJ is not disturbed and the renal pelvis is not surgically reduced. Since 2004, of 27 patients requiring surgery for UPJO, 7 underwent bypass pyeloplasty. The indications for surgery included increasing hydronephrosis or decreasing individual renal function in four, pain in two and pyelonephritis in one. The remaining 20 underwent a classic dismembered pyeloplasty. RESULTS: During a mean follow-up of 26 months, the anteroposterior diameter of the repaired kidney decreased by a mean of 55%. The individual renal function in the repaired kidney improved in two and remained stable in the remainder. CONCLUSION: These favorable initial results justify further exploration of this simplified technique and its adaptation for laparoscopic and robot-assisted approaches. Bypass pyeloplasty may be a more physiologic procedure in patients with mid to high insertion of the ureter.

The value of newborn urinary proteome analysis in the evaluation and management of ureteropelvic junction obstruction: a cost-effectiveness study.

PURPOSE: The cornerstone of management in newborns with ureteropelvic junction obstruction (UPJO) is serial imaging over time. Surgery is undertaken for disease progression. A marker of disease progression would select out those likely to progress for early surgery and diminish the intensity of imaging and follow-up in the remainder. Recently, urinary proteome analysis in the newborn has been reported to fulfill this aim. The objective of this study is to quantitatively evaluate the effect of this matrix of protein biomarkers on the overall cost-effectiveness (C-E) of UPJO evaluation and management. METHODS: A Markov process decision tree model (Tree Age Pro software, Boston, MA) is created to compare the current strategy (watchful waiting) to one incorporating a urine proteome analysis at birth as a marker of disease progression. The analysis includes the costs of surgery, imaging and office visits based on hospital charge data. We analyze a total of 53 variables. RESULTS: The incorporation of this marker of progression results on the average, in an incremental C-E gain of 8,000 US dollars per quality adjusted life year (QALY) per patient compared to the current strategy of watchful waiting. The results are not sensitive to variation of any of the probabilities including costs and quality of life parameters used for the base-case analysis. CONCLUSIONS: The incorporation of urinary proteome analysis in the initial evaluation of UPJO significantly reduces costs and increases the QALYs in this patient population. The test increases the odds of detecting UPJO progression from 1:3 to 1:1, while improving the overall C-E. These findings justify continued research in this area which in addition may have important applications in evaluating treatment outcomes.

Urologic problems of the neonate: an update.

During the last 2 decades of the twentieth century, maternal sonography became integrated into routine prenatal care. As a result, numerous anomalies are now detected in the fetus. This practice has had a profound influence on the presentation and natural history of urologic problems in the neonate. In an attempt to reflect the clinical scenario, this article is divided into two main parts: the first includes clinical questions raised by prenatally detected anomalies, abdominal masses, urosepsis, urinary retention, scrotal masses, and abnormal external genitalia; the second part is a discussion of specific anomalies with respect to evaluation and management, including controversies, and optimum timing for referral to a tertiary care center. Our knowledge regarding the pathophysiology and therefore treatment of these conditions is constantly expanding and changing.

Giant accessory female phallic urethral diverticulum.

Anomalies of the urogenital sinus have been described in association with male pseudohermaphroditism, bladder and uterine duplication, and a spectrum of external genital anomalies, including a female phallic urethra. The evaluation and optimal surgical management of these anomalies can be complex. We describe a case of a female patient with an accessory phallic urethra and a urogenital sinus anomaly. The presence of stenosis of the accessory urethral meatus led to the formation of a giant diverticulum with unusual features. The complete repair of the anomaly incorporated creation of labia minora from portions of the diverticulum.

Vesicoureteral reflux.

Vesicoureteral reflux, the abnormal flow of urine from the bladder into the ureter, is one of the most common congenital anomalies found in children. The association of vesicoureteral reflux with urinary tract infections and renal scarring has important clinical implications. New insights into pathogenesis and new surgical techniques are changing the approach to the management of this disorder.

Evaluation and management of genital anomalies in two patients with Klinefelter syndrome and review of literature.

OBJECTIVES: To present the evaluation and management of cryptorchidism and varicocele in patients with Klinefelter syndrome and review the literature. Recent advances in reproductive medicine have resulted in fertility in patients with Klinefelter syndrome. However, cryptorchidism and varicocele can affect the fertility potential on their own. METHODS: We present 2 cases and review the literature with an emphasis on the fertility potential. RESULTS: Germ cells were present in the testicular biopsy of an infant with cryptorchidism but not in the adolescent with a varicocele. The latter biopsy showed tubular sclerosis. CONCLUSIONS: The fertility potential of patients with Klinefelter syndrome and cryptorchidism may be preserved or enhanced by an early orchiopexy. However, the potential benefit of ligation of internal spermatic veins in patients with Klinefelter syndrome and a varicocele warrants further study. Cryopreservation should be considered early in adolescence or adulthood as germ cells become depleted at an accelerated rate after puberty.

Urologic problems of the neonate.

Maternal sonography is integrated into routine prenatal care, and numerous fetal anomalies are detected, with genitourinary anomalies the most common. This has profoundly influenced the presentation and natural history of neonatal urologic problems. This article is divided into two sections. The first addresses clinical questions raised by prenatally detected anomalies, abdominal masses, urosepsis, urinary retention, scrotal masses, and abnormal external genitalia. The second discusses evaluation and management of specific anomalies,including controversies, and optimum timing for tertiary care center referral. The selected anomalies include renal anomalies, tumors, the exstrophy complex, urogenital anomalies, ambiguous genitalia, posterior urethral valves, scrotal anomalies, spina bifida, and common urologic syndromes such as the triad syndrome. Readers are referred to urologic texts for additional information.

Ureteropelvic junction obstruction: an overlooked cause of cyclic vomiting.

Cyclic vomiting syndrome is an unusual cause of recurrent episodes of repetitive vomiting, particularly in children. Although in only a minority of cases can an underlying cause be found, each patient deserves a thorough evaluation for treatable conditions. We present four cases of cyclic vomiting syndrome caused by ureteropelvic obstruction. Surgical correction was followed by resolution of symptoms in all four patients.