bs_bs_banner International Journal of Urology (2015) 22, 514519 doi: 10.1111/iju.12712 Original Article: Clinical Investigation Concomitant anterior and posterior urethral valves in pediatrics: A single center experience over 12 years and long-term follow up after endoscopic treatment Abdol-Mohammad Kajbafzadeh, 1 Seyed Hossein Hosseini Sharifi, 1 Sorena Keihani, 1 Mohammad Hossein Soltani, 1 Afshin Tajali, 1 Alborz Salavati, 1 Seyedmehdi Payabvash 2 and Mehrzad Mehdizadeh 3 1 Pediatric Urology Research Center and 3 Department of Pediatric Radiology, Children s Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran; and 2 Department of Radiology, University of Minnesota Medical Center, Minneapolis, Minnesota, USA Abbreviations & Acronyms AUD = anterior urethral diverticulum AUV = anterior urethral valve DMSA = Tc-99m dimercaptosuccinic acid radionuclide scan NA = not available P detmax = detrusor pressure at maximum flow PUV = posterior urethral valve TUF = transurethral fulguration of valves TUR = transurethral resection of valves Trab = bladder trabeculation UDS = urodynamic study UTI = urinary tract infection V = vesicostomy VCUG = voiding cystourethrography VUR = vesicoureteral reflux Correspondence: Abdol- Mohammad Kajbafzadeh M.D., Pediatric Urology Research Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, No. 62, Dr. Gharib s Street, Keshavarz Blvd, 1419733151 Tehran, Iran (IRI). Email: kajbafzd@sina. tums.ac.ir Received 31 July 2014; accepted 12 December 2014. Online publication 16 February 2015 Objective: To report our 12-year experience with endoscopic management of patients with concomitant anterior and posterior urethral valves. Methods: We retrospectively reviewed the charts of patients referred to us for management of urethral valves from 2000 to 2012 to find cases with concomitant anterior and posterior valves. The diagnosis of valves was first suspected on voiding cystourethrography and confirmed by urethrocystoscopy. We collected available data on patients age at diagnosis, clinical presentations, ultrasound and urodynamic findings, and surgical treatments. The final outcome at last follow up was also recorded. Results: From 38 cases with anterior urethral valve, six (15.8%) presented concomitant anterior and posterior valves. The age at diagnosis in these patients ranged from antenatal diagnosis to 13 years. Initial presenting symptoms were recurrent urinary tract infection, incontinence, urosepsis and poor urinary stream. All valves were ablated by transurethral fulguration/resection using small-sized urethrocystoscopes. Among those with concomitant anterior and posterior valves, four patients had vesicoureteral reflux at presentation that resolved in two patients after valve ablation. One patient progressed to renal failure and required dialysis. Bladder hypercontractility and detrusor overactivity were the main urodynamic patterns in these patients. Conclusions: Concomitant anterior and posterior valves seem to be more prevalent than previously assumed, and might be missed on initial assessment. Oblique view voiding cystourethrography with full-length delineation of the urethra is of paramount diagnostic importance when obstruction is suspected. A meticulous urethrocystoscopy should follow for confirming the diagnosis and endoscopic ablation/resection of the valves. Key words: anterior urethral diverticulum, anterior urethral valve, bladder outlet obstruction, posterior urethral valve, urodynamics. Introduction Urethral valves are the main causes of bladder outlet obstruction in children. Although PUV is the most prevalent cause of obstructive uropathy, AUV and AUD, being approximately sevento 30-fold less frequent than PUV, can be equally devastating. 1,2 Arising from distinct embryological origins, the association of the two anomalies is rare with only a few cases reported in the literature. 3 Currently, many children with urethral valves are diagnosed by antenatal ultrasound studies; however, valves can remain undiagnosed until adolescence or even adulthood, and these patients might show a broad spectrum of clinical presentations. Clinical manifestations in AUV patients might be mild, and present with difficulty in urination in an adolescent boy, or might be severe enough to cause complete urinary retention, UTI, renal dysplasia or ascites. 4 Most pediatric urologists now consider primary endoscopic valve ablation as the gold standard for management of both posterior and anterior urethral valves, reserving vesicostomy or urinary diversion for those with persistent symptoms, or premature patients with very small urethral calibers. 4 However, little is known about the initial symptoms and treatment options in patients with concomitant AUV PUV. Also, urodynamic findings in this small group of children are rarely addressed. 514
Concomitant anterior and posterior urethral valves We have previously reported a neglected case of concomitant AUV PUV who underwent multiple surgeries while the presence of urethral valves was overlooked in his earliest VCUG. 5 In this study, we aimed to present our 12-year experience with 38 AUV patients with emphasis on the clinical history of six patients with concomitant AUV PUV. Methods Between 2000 and 2012, a total of 537 cases with PUV and 38 cases with AUV were diagnosed in our tertiary pediatric urology center among 27 000 referral cases. Information of patients with AUV was reviewed retrospectively after institutional review board approval to gather data on cases with concomitant AUV PUV. We collected available data on presentation age, presenting signs and symptoms, renal function tests, surgical treatment, and follow up information on patients with concomitant AUV PUV. We also reviewed radionuclide scans, urodynamic and uroflowmetry findings, VCUG, and ultrasound studies in these patients. A radionuclide Tc-99m DMSA scan was carried out in AUV PUV cases with suspected renal impairment to assess the functional status of the upper urinary tract. VCUG was also used to evaluate patients for the presence of VUR and grading it. UDS was carried out in all (except one) AUV PUV patients using a multichannel urodynamic system (Duet; Dantec Medical A/S, Skovlunde, Denmark), and included free voiding uroflowmetry in toilet-trained children. The P detmax was determined. Detrusor overactivity was defined as an uninhibited contraction of any magnitude that caused incontinence or significant urgency or any uninhibited contraction of >15 cm H 2 O during the filling phase, even with no leakage. Bladder hypercontractility was defined as uninhibited detrusor contractions and/or a P detmax >90 cm H 2 O. 6 Patients were reassessed 6 months after the procedure with a clinical examination, urine analysis and culture, serum creatinine, VCUG, ultrasonography, UDS, and uroflowmetry (if toilet trained). The investigations were repeated in the follow up as dictated by each patient s course. Primary valve ablation was the treatment of choice in all patients with AUV and/or PUV in our center. However, vesicostomy was carried out in three AUV-only and two AUV PUV patients before referral to our center. The initial indications for vesicostomy at the referral centers were unavailability of an adequate-sized cystoscope, severe UTI, urosepsis, and poor clinical condition despite bladder drainage through urethral catheterization and medical treatment. We fulgurated the urethral valves through a 67.5-Fr Wolf (Richard Wolf GmbH, Knittlingen, Germany) neonates urethrocystoscope using low-energy electrocautery equipment with a Bugbee electrode (cases 2 and 3). In older children, we used a 9-Fr pediatric resectoscope (Karl Storz, Tuttlingen, Germany) with a hook diathermy electrode to ablate the valves. Anterior valves were incised at 6 o clock; posterior valves were incised at 5, 7 and 12 o clock. In all patients, an indwelling urethral catheter was left in place for at least 2 days. VCUG was carried out after removal of the urethral catheter to assess the success of valve ablation and confirm obstruction relief. We used the MannWhitney U-test to compare age at diagnosis between AUV-only and concomitant AUV PUV patients. Categorical variables were compared using the χ 2 -test (Fisher s exact test). A paired t-test was used to compare P detmax before and after treatment in six AUV PUV patients. Statistical analyses were carried out using the SPSS 16.0 statistical software package (SPSS, Chicago, IL, USA). P-values <0.05 were considered statistically significant. Results Of a total of 38 patients with AUV, six had concurrent PUV (1.1% of PUV patients, or 15.8% of AUV patients). The baseline characteristics of AUV-only patients (n = 32) are compared with those with concomitant AUV PUV in Table 1. The mean age of AUV patients was 5.1 years (median 3.0 years, range 0 [antenatal diagnosis] to 17 years). The mean age at presentation in AUV PUV patients was 3.8 years (median 1.3 years, range 0 [antenatal diagnosis] to 13 years). The difference between the presence of hydronephrosis, VUR, bladder trabeculation and ages at diagnosis were not statistically significant between the two groups. AUV-only patients Clinical presentations in order of frequency were: poor urinary stream, postvoid dribbling, UTI, antenatal hydronephrosis and urinary retention. Of 14 cases with VUR (three unilateral and 11 bilateral), six resolved after valve ablation and eight patients were managed by endoscopic injection of bulking agent (Urocol). Endoscopic valve ablation was carried out in all cases including three patients in whom vesicostomy was carried out earlier. Renal function deterioration was noted in three cases despite improvement of hydroureteronephrosis and VUR probably as a result of renal dysplasia. No renal function abnormality was noted in other cases during their follow up. Concomitant AUV PUV patients Initial presenting symptoms were recurrent UTI, incontinence, urosepsis and poor urinary stream (Table 2). The presence of concomitant AUV PUV was first suspected on oblique view Table 1 Baseline characteristic of patients with AUV and concomitant AUV PUV AUV-only n = 32 AUV PUV n =6 P-value Age at diagnosis (years) 3.0 (1.09.0) 1.35 (0.18.5) 0.28 Hydronephrosis 20 (62.5%) 5 (83.3%) 0.64 Unilateral 7 4 Bilateral 13 1 VUR 14 (43.7%) 4 (66.7%) 0.39 Unilateral 3 3 Bilateral 11 1 Bladder trabeculation 13 (40.6%) 5 (83.3%) 0.08 Values presented as median (interquartile range). 515
AM KAJBAFZADEH ET AL. Table 2 Clinical presentation, radiological findings and treatment methods in six patients with concomitant AUV PUV Case no. Age at diagnosis Presenting symptom(s) Renal scan Hydronephrosis Trab VUR before surgery VUR after surgery Surgical method 1 2 years Recurrent UTI Left (grade III) Resolved V, TUR 2 3 Antenatal 43 days Antenatal hydronephrosis Urosepsis Right (grade V) Left (grade III) Persisted Persisted TUF V, TUF 4 5 6 2.5 years 7 years 13 years Dribbling, poor stream Incontinence Incontinence, UTI Left: no function Right: decreased function Right: single kidney Left: decreased function Right: scar NA NA NA Bilateral (grade III) Resolved TUR TUR TUR Also had high plasma creatinine concentration when referred to our center. Treated with bulking agent injection 6 months after valve ablation. VCUG (Fig. 1), and then confirmed and treated through urethrocystoscopy (Fig. 2). Cases 1 and 3 were referred to our center approximately 1 month after presentation of symptoms; vesicostomy was carried out as the initial salvage procedure in these patients, and was closed in the same session with transurethral ablation of valves. The level of plasma creatinine was initially above the normal range in three patients (cases 1, 2 and 3). Two of these cases had reduced DMSA renal uptake, and the other had a single kidney confirmed by ultrasonography. Case 2 was diagnosed antenatally with infravesical obstruction and underwent a two-stage procedure: at the first stage the presence of AUV was overlooked and PUV was fulgurated at a district hospital; postoperative VCUG confirmed successful ablation of PUV, whereas AUV persisted and fulguration of AUV was carried out 3 months later (Fig. 3). Case 6 presented with a long-lasting presentation with incontinence and recurrent UTI at the age of 13 years. He had a cusp-like AUV and an iris-like (Young s type III) PUV (Fig. 4). The other five cases all had type I PUV based on Young s classification. There was no evidence of surgical complications (e.g. urine extravasation, stricture formation and urethrocutaneous fistula) in successive imaging evaluations. Despite resolution of VUR in case 1, plasma creatinine increased continuously (up to 7.17 mg/dl), and he finally required dialysis and is now a candidate for renal transplantation. In cases 2 and 3, VUR persisted after valve ablation, and was treated by injection of bulking agent (Urocol) 6 months after the procedure; the serum creatinine levels normalized 1 year after procedure. The main pattern of preoperative bladder dysfunction in these patients was high Pdetmax, detrusor overactivity and hypercontractility (Table 3). The comparison between pre- and postoperative mean Pdetmax of five cases (cases 2 to 6) showed a significant decrease from 230.0 cmh2o to 101.2 cmh2o 6 months after obstruction relief (P = 0.03). Case 3 had bladder hypercontractility 6 months after the procedure, and follow up studies showed persistent Pdetmax >90 cmh2o and he is on anticholinergic therapy. The urodynamic studies of other children improved after the procedure, and they did not require anticholinergic therapy or intermittent catheterization. A uroflowmetry study in all toilet-trained patients showed abnormal voiding patterns before surgery (staccato and interrupted obstructive pattern); however, the voiding patterns changed to normal bell-shaped curves after valve ablation. Discussion In terms of obstructive uropathy, PUV is the most commonly encountered urethral anomaly in males. AUV and AUD should be also considered in the differential diagnosis, as the clinical presentation of these entities might be similar.2,4,7 However, the concomitant presence of AUV and PUV is rarely addressed in the literature, and our understanding of these patients is confined to a few case reports.3,5,815 In the present study, we reported six cases of concomitant AUV PUV with a focus on their clinical and radiological presentations, and urodynamic Fig. 1 Concomitant anterior (short arrows) and posterior (long arrows) urethral valves in (a) case 3, (b) case 4 and (c) case 6. 516
Concomitant anterior and posterior urethral valves Fig. 2 (a,c) Preoperative voiding cystourethrography showing anterior (short arrows) and posterior (long arrows) urethral valves. (b,d) Postoperative images of the same patients (cases 1 and 5). findings. Although the association is reportedly rare, this is the largest series of concomitant AUV PUV to date. Anterior urethral valve is a congenital mucosal fold located anywhere distal to the urethral sphincter and membranous urethra.4 As it is considered rare (in comparison with PUV), most related studies are case reports, and only a few larger series are published.4,7,16,17 AUV is usually found in the bulbar urethra (40%), penoscrotal junction (30%), pendulous urethra (30%) and very rarely in the fossa navicularis.17,18 It occurs either as an isolated entity or in association with a proximal Fig. 3 (a) Voiding cystourethrography of case 2 showed right-sided grade V VUR and urethral valves; the patient underwent posterior urethral valve ablation (long-arrow). (b) Voiding cystourethrography of the same patient 3 months after first surgery confirmed successful ablation of the posterior valve, whereas the anterior valve persisted (short arrow). diverticulum. The clinical presentation ranges from mild urethral dilatation and penile mass to bilateral hydroureteronephrosis and renal insufficiency, and depends on the presentation age and degree of obstruction.4 AUV can even induce histological changes in the bladder similar to PUV or clinical presentations of valve bladder syndrome.7 Many potential causes are suggested for the development of AUV. Some authors propose it represents an attempt at urethral duplication in the first 1214 weeks of intrauterine life.4 Incomplete focal development of the corpus spongiosum with bulging of the urethral mucosa as a result of ineffective support, defective fusion of the ventral folds over the urethral groove, failure of alignment between the proximal and distal urethra, and cystic dilatation of the urethral glands are other suggested mechanisms for the development of AUV.4,19 In contrast various theories exist for explaining the pathoembryology of PUV.20 Although the proposed etiologies for these two anomalies are thought to be different, the mechanism behind their concurrence remains widely unknown. Graham et al. reported one of the first cases of concomitant AUD and PUV (type I) diagnosed through urethrocystoscopy in a neonate with urinary retention.10 Zia-ul-Miraj also diagnosed another case of concomitant AUD and type I PUV using VCUG in an 18-month-old boy with voiding dysfunction and abnormal renal function; the valves were resected using a pediatric resectoscope and the patient was asymptomatic in a 1-year follow up.15 A recent article by Tran et al. reported two new cases of concomitant AUV PUV, and the authors found a total of five other cases with this diagnosis in a brief review of literature, although the total number is definitely larger than this.3 Taken together, this underscores our limited knowledge about the concurrent presence of anterior and posterior valves. The present study shows that concomitant AUV PUV might not be as uncommon as previously thought, diagnosed in 15.8% of our total AUV cases, and in almost 1% of patients with PUV. Regarding the diagnosis, an oblique view VCUG along with full-length delineation of the urethra is the most helpful diagnostic modality for evaluation of urethral valves. In the case of AUV, the anterior urethra appears dilated proximal to the valve, and narrowed distally. In VCUG, it might represent as either a linear filling defect along the ventral wall, a dilated urethra ending in a smooth bulge or an abrupt change in the caliber of the dilated urethra. After suspecting the presence of a urethral valve, urethroscopy should be carefully carried out to confirm the diagnosis. Under urethrocystoscopic vision, the AUV might appear as either a semilunar tissue flap (cusplike) or a circumferential iris-like membrane. It should be noted that the valves are likely to be missed on retrograde urethrography and also urethroscopy, as they might flatten on the urethral wall with retrograde flow.17,21 Exertion of manual pressure over the bladder to provide urinary flow during distal urethroscopy would be helpful to overcome this problem. Elevation of the cusp with the loop of a pediatric resectoscope can also facilitate identification of the lesion. In all cases of the present series (except one), dilatation of the posterior urethra with abrupt narrowing of the anterior urethra raised the possibility of concomitant AUV PUV. However, the definite diagnosis was made based on visualization of both valves under urethrocystoscopy. 517
AM KAJBAFZADEH ET AL. Fig. 4 Urethrocystoscopic view of urethral valves in case 6: (a) cusp-like anterior valve; (b) iris-like (Young s type III) posterior valve; and (c) arrow shows the verumontanum. The major goals in the treatment of urethral valves are: restoration of bladder function, control of infection, preservation of renal function, maintenance of continence, and elimination of obstruction and VUR. Transurethral ablation of valves is the treatment of choice for children with either AUVor PUV. 4,20 Vesicostomy and diversion methods could be saved for cases with intractable symptoms, or in resource-poor settings or immature neonates when the appropriate-sized instruments are not available. In some cases of large anterior diverticula, excision of the pouch and reconstructive surgery might be warranted. 4 It is common sense that when a congenital anomaly is diagnosed, the physicians should keep in mind the possibility of other concomitant anomalies. 22 The same principle applies to PUV and AUV; the presence of one valve can be easily missed unless the lesion is considered in boys with outflow obstruction. In one of our cases (case 2), PUV was fulgurated in another center, but the AUV was initially missed until the postoperative VCUG showed the second obstruction. Similarly, Kumar et al. reported that AUV remained undiagnosed after initial VCUG and cystoscopic treatment of PUV, and was diagnosed in postoperative VCUG complicating the treatment process. 11 Carvell and Mulik also reported that renal function deterioration after PUV resection in a 3-year-old boy led to recystoscopy and diagnosis of concomitant AUV. 9 In the report by Tran et al., AUVs remained unnoticed in both cases in the initial VCUG and were detected during the urethrocystoscopy for PUVablation. 3 Taken together, this evidence shows that concomitant AUV PUV might be easily overlooked when not kept in mind, and underscores the need for meticulous assessment of suspicious cases with VCUG and urethrocystoscopy. In the present study, patients with concomitant AUV PUV had a higher percentage of VUR, bladder trabeculation and hydronephrosis at presentation compared with AUV-only patients; however, these differences were not statistically significant. This could be attributable to the small number of AUV PUV cases limiting the power of the present study. We believe that concomitant presence of a proximal obstruction in AUV PUV patients could lead to more severe symptoms; however, this theory should be assessed in larger studies. The risk of impaired renal function in patients with PUV correlates with age at presentation, presence of bilateral VUR, renal dysplasia, recurrent UTI and bladder dysfunction. 20 Although the same could be true for concomitant AUV PUV, these associations remain unknown in these patients, as well as AUV patients, until larger series are available. In the present series, only case 1 had a poor renal outcome that could have been a result of the initial presence of renal dysplasia and high initial creatinine (3.3 mg/dl) in this patient; similarly three AUV-only cases that had renal dysplasia at presentation had renal function deterioration at follow up. However, the length of follow up is also an important factor, and the long-term renal outcome in these patients is still unknown. The main urodynamic patterns found in concomitant AUV PUV in the present patients were bladder hypercontractility and detrusor overactivity. We have previously reported the urodynamic patterns in AUV patients, and hypothesized that bladder dysfunction in AUV might be more benign than those observed in PUV, as the obstruction in AUV is more distal, and the enlarged urethra and diverticulum (if present) might compensate for the extra pressure on the bladder neck. 21 Table 3 Urodynamic findings and follow-up outcome of patients with concomitant anterior and posterior urethral valves Case no. P detmax (cmh 2 O) Urodynamic findings Follow-up duration Renal outcome Before After Before Final 1 42 No hypercontractility/overactivity 7 years Dialysis 2 170 83 Bladder hypercontractility No hypercontractility/overactivity 8 years Good 3 300 200 Detrusor overactivity, bladder hypercontractility, low compliance Bladder hypercontractility 5 years Good, renal scar persists 4 212 68 Detrusor overactivity, bladder hypercontractility No hypercontractility/overactivity 3 years Good 5 112 80 Detrusor overactivity, bladder hypercontractility No hypercontractility/overactivity 2 years Good 6 356 75 Detrusor overactivity, bladder hypercontractility No hypercontractility/overactivity 1 year Good The P detmax in urodynamic studies carried out before and 6 months after valve ablation. The major urodynamic findings of patients before valve ablation and at last study available. No urodynamic study was carried out. 518
Concomitant anterior and posterior urethral valves However in concomitant AUV PUV, the bladder is facing a double obstruction. Theoretically, the more proximal obstruction in these patients (i.e. posterior valve) might exert the same pressure on the bladder as in patients with isolated PUV. Though the number of patients in the present series was too small to make a conclusion, it is plausible that urodynamic findings in concomitant AUV PUV would be more severe than in AUV patients, and might be more similar to those in PUV patients. However, we were not able to test this hypothesis in the present study. We are aware that the present study faced its limitations. First, the retrospective design of study confined us to use the available data, and the crude values of some measurements were missing. The full panel of the urodynamic study was not documented, and we could only rely on P detmax and documented interpretations; however, normal UDS ranges in children are not standardized. We also did not have quantitative urodynamic and outcome measures from all AUV-only patients to compare it with concomitant AUV PUV. The length of follow up was also variable in the present study, and some renal function deteriorations may take more than 10 years to come into action, so we cannot conclude on the final outcome of concomitant AUV PUV. Last, but not least, uroflowmetric patterns (in toilet-trained children) were interpreted and documented according to a national uroflowmetry nomogram in children; it is known that subjective interpretation of these curves could be at risk of inter- and intraobserver bias and objective interpretation using computer-based software is recommended. 2325 The present findings are a reminder that once AUV is diagnosed, one should carefully consider the possibility of concomitant PUV, and vice versa. This series also underscores the importance of meticulous oblique view VCUG along with full-length delineation of the urethra. A careful urethrocystoscopy is the key to a definite diagnosis, and endoscopic ablation of valves confers a feasible and effective therapeutic method in these patients. Long-term and close follow up is required in cases of concomitant AUV PUV to assess renal and bladder function. Conflict of interest None declared. References 1 Jehannin B. Congenital obstructive valves and diverticula of the anterior urethra. Chir. Pediatr. 1990; 31: 17380. 2 Kajbafzadeh A. Congenital urethral anomalies in boys. Part II. Urol. J. 2005; 2: 12531. 3 Tran CN, Reichard CA, McMahon D, Rhee A. Anterior urethral valve associated with posterior urethral valves: report of 2 cases and review of the literature. Urology 2014; 84: 46971. 4 Paulhac P, Fourcade L, Lesaux N, Alain JL, Colombeau P. Anterior urethral valves and diverticula. BJU Int. 2003; 92: 5069. 5 Kajbafzadeh AM, Jangouk P, Ahmadi Yazdi C. Anterior urethral valve associated with posterior urethral valves. J. Pediatr. 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