58: Role of Transitional Urology
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The transitional urologist is charged with the care of pediatric urology patients as they progress to adult care. While the disease processes that compose transitional urology (Table 1) are themselves rare, they collectively amount to a significant burden. An estimated 3,573 babies were born in the United States in 2012 with spina bifida (2,765), posterior urethral valves (PUV, 493), bladder exstrophy (118), or cloacal anomalies (197).1 At the time of this writing, these patients are approaching adolescence and recent dramatic advances in the diagnosis and care of congenital urogenital anomalies and spinal dysraphism means that they will do so with unprecedented success. In the coming years, they will require transitional urologic care.
Table 1 Conditions that may be seen by the transitional urologist.
|Neurogenic Bowel and Bladder|
|Spina Bifida, Cerebral Palsy, Spinal Cord Injury, CNS Tumors|
|Bladder Exstrophy and Epispadias|
|Prune Belly Syndrome|
|Posterior Urethral Valves|
|Pediatric Urologic Cancer and Survivorship|
The purpose of this chapter is to define the role of the transitional urologist by discussing many of the issues that become or remain prominent as patients with congenital genitourinary disorders progress to adolescence and adulthood.
Renal preservation is a challenge common to many transitional urology patients. This section will focus on the representative cases of congenital anomalies of the kidney and urinary tract (CAKUT), in particular posterior urethral valves (PUV), as well as neurogenic bladder dysfunction.
CAKUT represents the leading cause of both chronic and end stage kidney disease in pediatric patients.2 A comparison of CAKUT patients with age-matched patients undergoing renal replacement therapy (RRT) for other renal disorders observed from 1990-2009 in a large European registry found that CAKUT patients initiated RRT at a median age of 31 years, versus 61 in controls.3 In the CAKUT cohort, the incidence of RRT initiation peaked between ages 15 and 19 years, supporting other data demonstrating that the renal function of CAKUT patients typically improves in infancy and remains stable until puberty, when decline is common.
In a report of adolescent and adult patients with both primary vesicoureteral reflux and renal dysplasia as well as obstructive uropathy and secondary dysplasia, Neild and colleagues observed that, while the burden of chronic kidney disease (CKD) is significant in CAKUT patients, the rate of loss of function in these patients is slower than that seen in peers with other forms of CKD.4,5 When progression of CKD was defined as -1.10 mL/min per year or greater, half of all CAKUT patients with eGFR of 50-60 mL/min and one-third of those with eGFR of 30-50 mL/min were found to be non-progressors. Faster rates of decline were seen in those with lower starting eGFR. Proteinuria was a significant indicator of progressive renal failure, while minimal loss of function was seen when proteinuria was limited.
Posterior Urethral Valves
Consistent with these findings, renal deterioration in PUV is understood to be a progressive, irreversible process set in motion in utero. In recent retrospective data with long term follow-up, between 30 and 50 percent of PUV patients developed end-stage renal disease (ESRD) by adulthood.6,7,8 In addition to performing routine surveillance of renal function and proteinuria, it is important to recognize that bladder dynamics change as these patients age. Significant changes in urination or continence or the finding of worsening or new hydronephrosis warrant evaluation with urodynamic studies (UDS).9,10 Following childhood management aimed at relieving obstruction, improving bladder compliance, and minimizing detrusor instability, adolescent PUV patients will commonly develop a combination of a poorly compliant, thick-walled bladder, impaired sensation of fullness, incomplete bladder emptying, upper tract dilatation, and nephrogenic diabetes insipidus referred to as “valve bladder syndrome.” Myogenic detrusor failure (decreased contractility and increased capacity) may follow this, indicated by increased post-void residual bladder volumes, new or worsening incontinence, or worsening dilatation of the upper tracts.
In light of this dynamic picture, management of PUV patients in the transitional period is dependent upon the state of bladder dysfunction. Patients with any combination of polyuria, poor compliance, and hypocontractility may benefit from double voiding, clean intermittent catheterization (CIC), overnight catheter drainage and, in certain cases, anticholinergic medications. Those with persistent outlet obstruction may benefit from alpha-adrenergic antagonists or require re-resection. When vesicoureteral reflux (VUR) persists in spite of appropriate management of the bladder and bladder outlet, anti-reflux surgery may be considered, understanding that these procedures are generally less successful in patients with dysfunctional bladders.11
Neurogenic Bladder Dysfunction
Neurogenic bladder dysfunction resulting from conditions like spina bifida represents another common etiology of renal deterioration throughout the transitional period and into adulthood. Despite the fact that most spina bifida patients are born with normal renal function, about 26% will have some degree of renal impairment by adulthood.12 This process of continuous renal deterioration coincides with changes in bladder dynamics that extend beyond childhood. In a retrospective series of 37 spina bifida patients, Almodhen and colleagues found that, following puberty, patients experienced significant urodynamic changes including increases in cystometric bladder capacity and compliance, as well as increases in maximum detrusor pressure and detrusor leak point pressure.13 These changes are theorized to have neurogenic (resulting from spinal cord tethering), anatomic (due to increasing outlet resistant resulting from prostatic growth or estrogenization of the female urethra), and/or behavioral (related to poor compliance with CIC) causes. While rates of VUR and hydronephrosis were not significantly different between the pre- and post-pubertal periods, it is important to recognize that these parameters change and, in the case of increased maximum detrusor pressure and detrusor leak point pressure, may result in transmission of high pressures to the upper tract and associated renal deterioration.
In light of the concern for ongoing renal decline in these patients, the Spina Bifida Association (SBA) recommends annual surveillance with serum creatinine and renal-bladder ultrasound for adolescent and adult patients, as well as serum chemistries including B12 for those who have undergone urinary reconstruction. For immobile patients with low muscle mass, an alternative measure of renal function such as cystatin C or nuclear medicine eGFR should be assessed.14,15 This is supported by the 2019 European Association of Urology (EAU)/European Society for Pediatric Urology (ESPU) guidelines for the management of neurogenic bladder in children and adolescents.16 The appropriate use of UDS in the transitional period is more controversial. The SBA makes no formal recommendations for the use of UDS, though some experts from high volume centers have individually recommended obtaining UDS at the beginning of the transitional period and/or for cause in the setting of recurrent UTIs, bladder pain, or new or worsening incontinence or upper tract dilatation thereafter.17,18 The EAU/ESPU guidelines suggest more regular screening with biannual UDS in adolescence and adulthood.
The mainstays of management of neurogenic high-pressure voiding in the transitional patient are similar to those recommended in childhood, including CIC, anticholinergic medications and, in cases refractory to medication, intradetrusor botulinum toxin A (Botox) injection. While all are generally low risk, each carries side effects to consider. Chronic CIC increases the risk of bladder or urethral trauma and resultant urethral stricture, perforation, or meatal stenosis. Furthermore, colonization of the urinary tract puts CIC patients at increased risk not only for UTIs, but also for overtreatment of asymptomatic bacteriuria and resultant multi-drug resistance, drug-related side-effects, and opportunistic infections.19,20 Anticholinergic medications have been shown to reliably reduce detrusor overactivity and decrease intravesical pressure21,22 and their use in pediatric neurogenic patients is broadly supported.14,16 Beta-3-adrenergic agonists have the advantage of eliminating anticholinergic side-effects and are commonly used as both alternatives and adjuncts to anticholinergics, though published clinical experience remains limited. Botox injection every 6-12 months may be considered in cases refractory to medications. Clinical experience suggests that Botox is most effective in suppressing detrusor overactivity and may be less effective when poor compliance is the primary issue.23,24
Patients who fail or are otherwise unfit for conservative management of high-pressure voiding may be candidates for augmentation cystoplasty, which carries the benefit of both increasing surface area and decreasing contractility in the bladder. The use of bowel segments carries with it the risk of numerous complications (Table 2), including metabolic disarray, UTIs, reservoir stones, bowel obstruction, and malignancy. Furthermore, augmented bladders and pouches are susceptible to perforation, which can result from overdistension or direct puncture with a catheter. Perforation is a life-threatening emergency, presenting spontaneously in 8.6% of patients in a large retrospective series of 500 cases of bladder augmentation reviewed by Metcalfe and colleagues.25 In this group, roughly one-third of perforations occurred within 2 years of surgery, another third between post-operative years 2 and 6, and the final third more than 6 years following augmentation. While increased risk of perforation has traditionally been attributed to numerous clinical variables including choice of bowel segment, bladder neck closure, and ischemic injury to the augment, a 2016 analysis of transitional and adult bladder augmentation patients found that spontaneous bladder rupture occurred at a significantly higher rate (22%) in patients with a history of alcohol abuse and/or noncompliance versus peers with neither of these risk factors (2%).26
Table 2 Complications of enterocystoplasty.
|Urinary Tract Infections|
|Urinary Tract Calculi|
|Diarrhea and Gastrointestinal Malabsorption|
|Channel Stenosis, Stricture, or False Passage|
|New Urinary Incontinence|
|Malignancy of Bowel or Bladder|
Voiding and Continence
The scope of voiding dysfunction in the transitional patient is broad, including structural (PUV) and neurogenic (detrusor-sphincter dyssynergia) bladder outlet obstruction; congenital anomalies of the bladder, bladder neck, or urethral sphincter (prune belly syndrome, bladder exstrophy, cloacal malformations); and abnormal smooth muscle function, whether primarily neurogenic or resulting from trauma, stones, infections, or previous treatments or surgeries.
A multicenter retrospective study of over 400 adolescent or adult spina bifida patients found that 66% experienced urinary incontinence, with 40% having either continuous or frequent leakage.27 In 2017, a group from the University of Indiana reported the results of a large survey study finding urinary incontinence to be a significant independent predictor of lower health related quality of life (HRQOL) in adult spina bifida patients, with increasing amount of urinary incontinence associated with worse HRQOL.28
Management of urinary incontinence in the transitional patient may be tailored depending on the etiology. If high end fill pressures are the primary driver of incontinence, as may be the case in both congenital outlet resistance like PUV as well as various forms of neurogenic bladder dysfunction, methods aimed at improving bladder compliance and capacity (as detailed in the previous section) may alone be effective. Of note, given that bladder dysfunction resulting from PUV is dynamic and often ends with a capacious, hypotonic bladder, augmentation is less commonly advisable in this population.
If incontinence is attributable primarily to an incompetent bladder outlet, this may be addressed with surgery of the bladder neck, whether it be a formal reconstruction, sling procedure, artificial urinary sphincter placement, or instillation of bulking agents. It is critical to note that treating incontinence in spina bifida patients introduces the risk of unmasking high voiding pressures and VUR, even in patients for whom this was not previously detected.29 For this reason, concomitant bladder augmentation is advisable when performing procedures to increase bladder outlet resistance, except in carefully selected patients who are counseled preoperatively on the need for close postoperative follow-up and potential need for a delayed augmentation.
Finally, catheterizable channels often benefit this patient population—in cases of immobile female patients for whom urethral catheterization is challenging as well as in patients for whom a previous anti-incontinence procedure precludes catheterization per urethra. These surgeries are increasingly complex as patients age; obesity and prior surgeries limit choices for bowel segments and increase the likelihood of complications.30,31
Pregnancy poses a number of unique challenges to transitional urology patients, particularly those with reconstructed or augmented urinary tracts. Ideally, patients should be counseled on this prior to becoming pregnant. Patients with enterocystoplasties should be made aware that urine HCG tests may be falsely positive up to 57% of the time, likely attributable to reservoir mucous and enzymes reacting with the testing reagent.32,33 These patients should therefore use serum HCG tests to minimize false positives. Patients with preexisting renal dysfunction are at greater risk for numerous pregnancy complications including accelerated loss of renal function and should be counseled on this.34 If and when pregnant, these patients’ renal function should be closely monitored. Patients with solitary kidney in particular should be aware of the increased risk of nephrolithiasis in pregnancy. Obstruction should be considered early in the evaluation of kidney injury in these pregnant patients.
The mass effect from the gravid uterus itself may challenge the vascular supply to a bowel augment, obstruct reimplanted ureters or catheterizable channels, or lead to bowel obstruction, ventriculoperitoneal (VP) shunt compression, urostomy stenosis or prolapse, or a parastomal hernia. In patients without bladder neck closure, the attendant shift in pelvic anatomy may lead to de novo or worsening urinary incontinence.
Pregnancy is associated with an increased risk of urinary tract infection (UTI) in all patients. This is especially true of reconstructed patients who, on top of a baseline elevated UTI risk, must contend in pregnancy with increased mucous secretions and potential difficulty with catheterization. It is not uncommon that these patients require continuous urinary drainage at some point during pregnancy due to inability to catheterize.35 Patients with a reconstructed urinary tract, particularly those involving bowel segments, are at increased risk of pyelonephritis during pregnancy,36,37 which can lead to preterm labor, fetal loss, or fetal growth impairment.
There are special considerations for both vaginal delivery and Cesarean section (C-section) in many transitional urology patients.
In order to be eligible for vaginal delivery, bony and muscular anatomy, which is often altered in patients with spina bifida and other congenital anomalies, must permit adequate hip abduction and room for fetal transit through the pelvis. Furthermore, patients with spinal dysraphism must be able to generate the coordinated muscular contraction necessary for pushing in the later stages of delivery.37 Finally, patients with a history of anti-incontinence surgery or bladder neck reconstruction should be made aware that a prolonged vaginal delivery poses a risk of injury to pelvic floor support and continence mechanisms. Should these patients pursue vaginal delivery, prolonged labor should be avoided if this can be accomplished safely.
C-section in patients with enterocystoplasties must be carefully planned and a surgeon familiar with the reconstructed anatomy must be accessible in case of any injury to the reconstructed bladder or its vascular supply. In a series of pregnant patients with prior urinary reconstruction, Hensle and colleagues report that C-section via a midline incision routinely permitted distraction of the reservoir or augmented bladder towards the area of bowel harvest and safely away from the gravid uterus.35 A midline incision is therefore traditionally recommended, though a recent series of female exstrophy patients from Dy and colleagues at the University of Washington reported that using a classical vertical uterine incision with a paramedian skin incision contralateral to the stoma was also routinely successful.38 Finally, the presence of a VP shunt should be considered a reason to avoid C-section unless otherwise necessary, given the risk of shunt infection associated with abdominal surgery.37
Urinary Tract Calculi
The transitional urological patient may have a number of risk factors for developing urinary tract stones that are attributable to both the reconstructed urinary tract and associated comorbidities. Urinary retention, VUR, and the use of catheters with attendant increased UTI rates are all associated with heightened stone formation. Patients with reconstructed urinary tracts experience urinary stasis while enteric segments contribute mucous, which, along with sutures and staples, may serve as a nidus for stones. These patients are also at greater risk for enteric hyperoxaluria given prior bowel resection.
Spina bifida patients may be particularly susceptible to stone disease throughout the urinary tract due to sequelae of immobility – namely bone resorption causing hypercalciuria and obesity leading to urinary acidosis. Spina bifida patients with sensory deficits who develop obstructing stones may present with atypical symptoms such as headaches, nausea, or autonomic dysreflexia, or may have no symptoms at all prior to developing sepsis or renal injury. Similarly, an obstructing stone in a patient with a renal transplant may present only as diminished urine output. It is thus necessary to have a high index of suspicion for obstructing stones in these patients.
Work-Up and Medical Management
As with all pediatric patients, transitional patients who develop urinary tract stones warrant evaluation with 24-hour urine collection. Preliminary recommendations may nonetheless be made based on the predisposing condition. Patients with colonized urinary tracts are more likely to develop infection-related stones (struvite, carbonate apatite, or calcium phosphate); immobile patients are at risk of calcium-based stone formation resulting from osteodystrophy and uric acid stones relating to obesity; and those with bowel augments or pouches are at increased risk of developing enteric hyperoxaluria.39,40,41
The role of thiazide diuretics, prophylactic antibiotics, allopurinol, and alkalinizing agents in minimizing stone formation may be extrapolated from literature pertaining to the general population, though have not been rigorously evaluated in transitional patients who suffer from dysfunctional voiding and/or have undergone bladder augmentation. The use of regular high volume (≥240mL) irrigation has been shown in at least two clinical series to reduce bladder stone recurrence in patients with augmentation cystoplasties. Hensle and colleagues advised a regimen of twice weekly irrigation with saline and once weekly with gentamycin, while the Husman group used daily saline irrigations.26,42
Urolithiasis is among the most common indications for surgery in transitional urology patients.17,18 When it comes to surgical management of stones, transitional urology patients typically require additional consideration and, in many cases, multiple surgeries in order to become stone-free. Positioning and access may be challenged by contracture, musculoskeletal deformities, and obesity. Furthermore, in susceptible patients, autonomic dysreflexia must be considered a significant risk with any procedure involving filling or instrumenting the urinary tract.
Patients who experience urinary stasis, recurrent UTIs, and/or have urinary tracts including bowel segments are disproportionately susceptible to lower tract stones.41,43 In operating for lower tract stones, percutaneous and open approaches have been favored for patients with a history of bladder neck closure or reconstruction for whom urethral access is either impossible or ill-advised, as well as those with large stones. Instrumenting the catheterizable channel in these patients is not recommended in order to avoid damaging the continence mechanism. Current data generally support a percutaneous approach in all but extenuating circumstances, given comparable recurrence-free rates and favorable postoperative lengths of stay in comparison with the open approach.44,45,46
Patients with urinary dysfunction are at elevated risk for developing cancer in their bladders, whether they have undergone augmentation or not. These patients experience higher rates of recurrent UTIs and bladder stones, and often have chronic indwelling catheters and/or reconstructed bladders, which are themselves risk factors for bladder and/or colon cancer.47,48 Furthermore, these patients suffer from presenting atypically and at advanced stages, likely leading to worse outcomes. Austin and colleagues reported on 8 cases of spina bifida patients treated for bladder cancer at median age of 41 years, of which just one patient had undergone augmentation cystoplasty.49 These patients commonly presented with atypical symptoms including urosepsis, renal failure, difficult catheterization, more frequent UTIs, and sterile pyuria. While the majority presented with gross hematuria, most of these patients had experienced episodes of gross hematuria in the past. At the time of diagnosis, 88% had either tumor stage 3 or greater or lymph node metastases.
The mixing of colonic and urothelial mucosa, prolonged exposure of enteric mucosa to urine and, in the case of ureterosigmoidostomies, the mixing of urine and feces have long been theorized to foster an oncogenic milieu in the reconstructed bladder. This was supported by evidence that tumors or polyps develop in as many as 41% of patients with ureterosigmoidostomies on long term follow-up,50,51,52,53 which have since mostly fallen out of favor. By comparison, Husmann and Rathbun have reported a malignancy risk (colonic and urothelial) of 1.5% per decade of life following ileocolonic augments performed for a range of etiologies of bladder dysfunction.54,55 In patients specifically with gastric cystoplasties, the risk is likely greater: 2.8% per decade, as reported by Vemulakonda and colleagues.56
With an understood increased risk of malignancy in all patients with dysfunctional bladders, the role that augmentation with bowel segments plays in amplifying this risk remains in question. In a review of over 20 years of registry data, Higuchi and colleagues compared cancer risk in patients who had undergone ileal or colonic cystoplasty for bladder dysfunction resulting from neurogenic cause, exstrophy, and PUV against that in patients matched for age, gender, and etiology of bladder disfunction who had not undergone augmentation and were managed with CIC and anticholinergic medications alone.57 They found no significant difference between these groups in bladder cancer incidence, age of diagnosis, tumor stage, mortality rate, or median survival. In all cases, cancer developing in these patients with congenital bladder anomalies presented at a younger age, with more advanced disease, and was associated with worse survival.
Increased cancer risk had led many urologists to recommend routine screening with cystoscopy and/or biopsy, and a possible role for urine cytology has also been discussed.56,58 Recent clinical experience has called into question the value of routine screening, however. In a 2011 study from the Mayo Clinic group, 250 surveillance cystoscopies over 5 years in patients 10 years post-enterocystoplasty found no malignant lesions.59 Notably, the performance of urine cytology for screening was also poor in this group, with a specificity of 90% compared with 99% in the general population, supporting previous data suggesting that bowel segments meaningfully confound cytological analysis.60,61 Given the aggressiveness of tumors generally found in this type of patient and the low diagnostic yield of cystoscopy in this series and others,62 the authors concluded that routine cystoscopy was unlikely to detect early-stage cancer and therefore a poor screening tool. This group has instead recommended performing endoscopy only when certain criteria are met (recurrent UTIs; gross hematuria and/or greater than 50 rbc/hpf on urinalysis; bladder pain; concerning radiographic findings; or otherwise beginning at age 50 for patients with colonic augments, consistent with screening recommendations for colonoscopy). A similar recommendation is endorsed by the Spina Bifida Association 2018 guidelines, which recommend performing cystoscopy in adult patients with bladder augments in the event of clinical changes in the upper or lower urinary tracts including increasing incontinence, gross hematuria, recurrent UTIs, pelvic pain, or a renal transplant with known BK/polyomavirus.14
Across fields, children with special health care needs are underserved, with only 40% receiving adequate services according to the 2009-2010 US National Survey of Children with Special Healthcare Needs.63 It is likely that transitional patients in need of genitourinary care are no exception. A 2014 study of 24 patients with neurogenic bladder or congenital genitourinary abnormalities referred to a transitional care clinic found that changes in management were required in 70.8% of cases, with surgical management required in 58.3%, indicating a staggering prevalence of undertreatment in these patients.17 In the case of spina bifida, even when patients are directed to follow up in a multidisciplinary clinic for transitional urologic care, the rate of successful transition has been demonstrated to be as low as 40%.64 Lack of insurance, under-insurance, or lapses in coverage may be accountable for as many as half of missed appointments in transitional urology patients.65
The consequences of inadequate surveillance and undertreatment in this group are substantial. In addition to the potential for major morbidity in the short- and long-term, it has been demonstrated that transitional patients with inadequate care are more likely to rely on emergency care64 and frequently require preventable hospitalization for urinary issues.66 In efforts to minimize gaps in care and maximize patient comfort and the impact of clinic visits in the transition period, a number of centers have established clinics specializing in transitional genitourinary care. Providers have described strategic clinic location64 and other best practices for transitional visits.17,18,65,67,68
While it remains unclear which provider-related strategies are most effective in optimizing transitional care, it is now widely recognized that preparing the patient for adult life is critical to a successful transition. In addition to preparation for sexual and reproductive function and establishing continence when possible, this means enabling the patient to become the primary steward of his or her own care through education about independent living, medication management, and insurance coverage. Due to the multisystem nature of disease in transitional patients and the diversity of considerations relating to continuity of care, transitional urology is necessarily a team sport, often requiring contributions from additional providers across fields, including nephrology, endocrinology, gynecology, neurosurgery, social work, nutrition, and specialized nursing.
The role of the transitional urologist is multifaceted, including prevention of acute pathology, preservation of organ function, and enabling the progression of pediatric patients to adulthood. The establishment of best practices remains a work in progress, as clinical experience with these patients in adolescence and adulthood grows.
- Close observation of patients with urologic malformations and neurogenic bladder is critical in the transitional patient to ensure preservation of renal and bladder function.
- The presence of an enterocystoplasty puts patients at risk for numerous severe complications that may arise in the transitional period, including sepsis, bladder rupture, and malignancy.
- Pregnancy planning in the transitional patient should consider unique maternal health risks as well as anatomic and neurologic barriers to delivery. If a C-section may be required or is preferred, this should be planned with careful consideration of the reconstructed anatomy and an expert available to assist in the event of complications.
- Urinary tract stones and malignancy should be considered in the event of clinical changes including new or increasing incontinence, gross hematuria, recurrent UTIs, and pelvic pain in transitional patients with voiding dysfunction, particularly those who have undergone bladder augmentation.
- Good transitional care includes not only disease prevention and management, but also preparation for adult life.
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- Spina Bifida Association. Guidelines for the Care of People with Spina Bifida. 2018. DOI: 10.1016/j.pedn.2019.01.007. link
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- Wühl E, Stralen KJ van, Verrina E, Bjerre A, Wanner C, Heaf JG, et al.. Timing and Outcome of Renal Replacement Therapy in Patients with Congenital Malformations of the Kidney and Urinary Tract. Clin J Am Soc Nephrol 2013; 8 (1): 67–74. DOI: 10.2215/cjn.03310412.
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- Holmdahl G, SillÉN U. Boys With Posterior Urethral Valves: Outcome Concerning Renal Function, Bladder Function And Paternity At Ages 31 To 44 Years. J Urol 2005; 174 (3): 1031–1034. DOI: 10.1097/01.ju.0000170233.87210.4f.
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- López Pereira P, Miguel M, Martı́nez Urrutia M.J., Moreno JA, Marcos M, Lobato R, et al.. Long-term bladder function, fertility and sexual function in patients with posterior urethral valves treated in infancy. J Pediatr Urol 2013; 9 (1): 38–41. DOI: 10.1016/j.jpurol.2011.11.006.
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