Pediatric Urology Concomitant Anterior and Posterior Urethral Valves: A Comprehensive Review of Literature Sorena Keihani and Abdol-Mohammad Kajbafzadeh Posterior urethral valves (PUVs) are the most common cause of infravesical obstruction in children, whereas anterior urethral valves and/or diverticula (AUV/D) are less commonly encountered. Concomitant AUV/D and PUV is believed to be very rare and may be missed on the initial evaluation. In this review, we provide brief information on embryology of AUV/D and PUV to explain the concurrent presence of these anomalies. We also summarize the information on published cases of concomitant AUV/D and PUV in the English literature with a special focus on diagnosis and the importance of both voiding cystourethrography and careful urethrocystoscopy. UROLOGY 86: 151e157, 2015. 2015 Elsevier Inc.
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osterior urethral valves (PUVs), with an incidence of 1 in 5000 to 8000 male births, are the most common cause of congenital lower urinary tract obstruction.1 Less commonly encountered are obstructive anomalies of the anterior urethra with anterior urethral valves (AUV) and/or diverticula (AUV/D) at the top of the list. Although 10-30 times less prevalent than PUV, these conditions may be similarly devastating and need prompt diagnosis and treatment in early stages.2 A more challenging but less known phenomenon is double urethral obstruction by concomitant anterior and posterior valves. A deeper view on concurrent presence of these conditions may shed some light on the largely unknown etiology and embryology of both AUV/D and PUV. However, our understanding of concomitant AUV/D and PUV is limited to few case reports, and little is known about the presentation, diagnosis, and management of these patients. This limited knowledge together with the assumed rarity of this condition, at least in the published literature, may lead to underdiagnosing of concomitant AUV/D and PUV in children. We hereby review the literature on concomitant AUV/D and PUV to summarize the clinical presentation, diagnosis, and treatment of this condition with a focus on pitfalls in initial workup. We also review some of the embryologic explanations behind AUV, anterior urethral diverticulum (AUD), and PUV in an attempt to explain the concurrence of these conditions based on the current evidence.
Financial Disclosure: The authors declare that they have no relevant financial interests. From the Pediatric Urology Research Center, Children’s Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran Address correspondence to: Abdol-Mohammad Kajbafzadeh, M.D., Pediatric Urology Research Center, Children’s Hospital Medical Center, Pediatric Center of Excellence, No. 62, Dr Gharib Street, Keshavarz Boulevard, Tehran 1419733151, Iran. E-mail: [email protected] Submitted: December 27, 2014, accepted (with revisions): February 17, 2015
ª 2015 Elsevier Inc. All Rights Reserved
METHODS We reviewed the literature by searching the MEDLINE (PubMed) electronic database and Google Scholar through November 2014. We used various combinations of text words such as “anterior urethral valve,” “anterior urethral diverticula,” “posterior urethral valve,” “double obstruction,” and “infravesical obstruction” to identify relevant studies. We also used the “related articles” function in MEDLINE to find related studies. Articles were screened based on titles and abstracts, and relevant articles were selected for a full review. The reference list of related articles was also screened to find additional articles. Online-only articles or those not indexed in MEDLINE were also included. Non-English publications were excluded, unless an informative abstract was provided in English.
ANTERIOR URETHRAL VALVE VS ANTERIOR URETHRAL DIVERTICULUM Which came first, AUV or AUD? Little consensus exists on the use of AUV and AUD terminology in the literature that leads to remarkable inconsistency in different reports. One theory attempts to explain this controversial subject by proposing that a spongy defect in urethra leads to formation of AUD, and the anterior lip sometimes acts as a valve when the diverticulum is filled.3-5 This would also explain the situations that AUD is present without any valve effect. However, another theory sees AUV as the initial insult causing obstruction and turbulence in the proximal urethra leading to urethral bulging and diverticulum formation.6 This theory would better account for AUVs without a diverticulum.7,8 It can be suggested that an early obstructive AUV may affect the normal differentiation of proximal spongy tissues and explain the hallmark defects seen in AUD. A dilated or ruptured Cowper cyst should be differentiated with AUV and AUD, although this condition may share some of the characteristics of AUD and an early obstructive insult may be the underlying cause for its dilation. http://dx.doi.org/10.1016/j.urology.2015.02.019 0090-4295/15
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In 1978, Firlit et al9 provided a classification for AUV that categorized diverticula as a subtype of AUV with the same pathology. In this classification, type 1 roughly represents AUV without diverticula and AUV types 2-4 represent AUD with or without changes in the upper tract.9 The classification however does not cover AUVs that cause upper tract anomalies in absence of an AUD.8 However, some other authors clearly differentiate between AUV and AUD and believe that these are distinct entities.10,11 As proponents of this theory, Brueziere and Guerrieri10 presented their clinical and surgical experience in 14 cases and concluded that AUD develops outside of the corpus spongiosum and should be treated by open surgical repair, whereas in AUV, the distention is covered by corpus spongiosum and should be treated endoscopically. However, what the authors referred to as “outside of corpus spongiosum” may simply represent incomplete spongy tissue formation with fibrotic and rudimentary remnants similar to pathologic findings of Dorairajan.12 Considering these inconsistencies, we used AUV/D terminology in this review to represent AUV and/or AUD, unless otherwise specified. AUD represents a ventral saccular dilation of the urethra with defects in the corpus spongiosum as its hallmark. The size of the diverticulum is variable based on the degree of tissue defect and probably duration of obstruction and pressure overload on the adjacent tissues. In pathology, a thin epithelial lining covers the diverticulum that is surrounded by a fibrotic and rudimentary spongy tissue.12 The proximal corpus spongiosum may also show degrees of abnormality and fibrosis.12 The distal lip of AUD may act as a “flap-valve” or have a “gate-effect” obstructing the urine flow during urination.13 This probably happens when the diverticulum fills with urine and the pressure on the distal flap pushes it against the urethral roof to occlude the urethra.2,14,15 AUV, if not associated with AUD, mostly represents a “cusp-like” or “iris-like” mucosal remnant in the ventral aspect of the urethra, with no or minimal bulging proximal to it. However, one can argue at what level of dilation a proximal bulging fulfills the criteria to be called a diverticulum, if presence of a spongy defect is not evident or assessable. These anomalies occur anywhere in the anterior urethra, most commonly at the penoscrotal junction and also the penile or bulbar urethra.
EMBRYOLOGY Normal Development of External Genitalia in Male Despite the recent advances in molecular aspects of embryology, our knowledge about the exact mechanisms in the development of urogenital tract is still limited. Complex interactions between androgen-independent, androgen-dependent, and hormonal and environmental factors play a role in external genitalia differentiation.16 During early ambisexual (indifferent) phases, urorectal septum develops toward the cloacal membrane, urogenital and labioscrotal folds appear, and the primary perineal 152
body and genital tubercle form mostly in a hormoneindependent manner.16 Under the effect of Y chromosome and androgens, masculine differentiation of external genitalia continues. Urethral plate and mesenchymal phallic tissue abut the genital tubercle and elongate caudally to form the phallus. The urethral plate canalizes to form the urethral groove (from endothelial origin), whereas urogenital folds (from mesothelial origin) migrate medially and meet at the midline to complete the cylindrical structure of the phallus and penile urethra from behind forward. The mesenchymal urogenital folds later differentiate into vascular erectile tissues (corpus spongiosum and corpora cavernosa). The cranial part of urogenital sinus also forms the membranous and prostatic urethra. Early in development, the Wolffian (mesonephric) ducts insert into the cloaca anteriorly as solid structures but soon they undergo canalization and migrate posteriorly and cranially to finally lie at the level of future verumontanum.13 This gradual migration leaves “snailtrack” marks in the urethra toward verumontanum that are absent in total agenesis of Wolffian ducts.13,17 Most caudally, the cells grow to form glans penis, and canalization begins at the summit of glans by ectodermal ingrowth to meet the urethra formed by the urethral plate proximal to fossa navicularis. However, the formation of this part is more controversial and some disputed the ectodermal origin and proposed that the proximal urethral plate is also responsible for formation of the urethra in fossa navicularis by endodermal-mesenchymal interaction and endodermal differentiation.18,19 Embryology of Anterior Urethral Valve and/or Diverticula Several theories are proposed considering embryologic origin of AUV/D. An early transient obstruction in the anterior urethra (eg, stenosis or preputial narrowing) was first proposed by Watts in 1906 (cited in the study by Williams and Retik14). Others also proposed that incomplete closure of urogenital folds or a failed attempt for urethral duplication might be the cause.2,14 In 1886, Kaufman attributed AUD to a junctional obstruction between glandular and penile urethra (cited in Williams and Retik14). Similarly, Stephens in 199313 found obstructed glandular urethra in autopsies of 2 patients with megalourethra and proposed that delayed canalization of glandular urethra might be the main culprit. However, Williams and Retik14 questioned most of these theories and advocated those proposed by Suter and Johnson that congenital dilation of periurethral glands or cysts that open into the ventral urethra is the underlying cause of AUD. Similarly, McLellan et al15 supposed that rupture of Cowper cyst or syringocele leads to AUD formation. Although a promising theory, one should be skeptical that why the glands were prone to dilation in the first place and if any preceding event (eg, a transient obstruction) led to incomplete spongy tissue formation around the gland. Additionally, this theory does not fully explain the valves in more distal parts and also isolated UROLOGY 86 (1), 2015
valves without a diverticulum (type 1 AUV in Firlit classification). Normally, the urogenital folds envelope the bulbar urethra and differentiate into vascular erectile tissues. Incomplete migration of mesenchymal cells to form the ventral spongy tissue may render some parts rudimentary with inadequate support and provide an appealing theory to explain AUD. When differentiation of the urogenital fold into spongy tissue is totally or largely absent, profound saccular dilation of the penile urethra arises known as scaphoid-type megalourethra. When the defect is more extensive and involves one or both corpora cavernosa, fusiform megalourethra evolves. Embryology in Concomitant AUV/D and PUV Many authors consider AUV/D and PUV as clearly distinct conditions with distinct embryologic origins and explain concomitant AUV/D and PUV as a rare coincidence of 2 unrelated congenital anomalies.7,20-22 However, a different approach would be following the Occam’s razor or diagnostic parsimony to explain the embryology of concomitant AUV/D and PUV. This approach may also provide some explanation for concurrent presence of PUV with megalourethra23-25 and to a lesser extent concurrent presence of prune belly syndrome and anterior urethral anomalies.26-29 Taking all these anomalies into consideration, the most reasonable explanations lie in the mesenchymal origin and an early obstructive insult. During embryologic development, the urogenital folds fuse proximally to distally to form the urethra and abut on the glans. Also, the Wolffian ducts course craniomedially to absorb into the verumontanum.13 Incomplete reabsorption of mesenchymal tissue in the anterior urethra and abnormal migratory passage or defective absorption of the Wolffian duct in the posterior urethra during these stages may leave remnants in the length of the urethra acting as valves. Similarly, any delay in this process may cause a transient obstruction and hinder the normal differentiation of proximal tissues and, for example, cause an arrest in normal spongy tissue formation. This is in line with the aforementioned theory on delayed or arrested canalization of glandular urethra causing extensive proximal defects like megalourethra. It can be hypothesized that if the obstruction is severe and early enough, the developmental process of posterior urethra and upper tract may also be affected in a way that the defects persist even after spontaneous resolution of obstructing site. In 1991, Ortiz et al30 also addressed this holistic approach when they observed a child with Russell-Silver syndrome with multiple anomalies including AUD, PUV, and hypospadias. They linked PUV and spongy defects found in AUD and supposed that inadequate or delayed testosterone production may be involved in this process, a theory that received little attention afterward.30 However, the recent reports of concomitant AUV and PUV with hypospadias may further support this theory.20,31,32 UROLOGY 86 (1), 2015
CONCOMITANT AUV/D AND PUV Available Studies From a statistical viewpoint, one may estimate the prevalence of concomitant AUV/D and PUV to be exceedingly rare by multiplying the incidence of AUV/D by that of PUV. However, this calculation method assumes that no biological or clinical relationship exists between the 2 entities that may not be essentially true. Even if we do not consider these anomalies embryologically related and a result of an underlying intrauterine developmental defect, it is well known that when a congenital anomaly of the urinary tract is present, there is a good chance to find other anomalies. In reviewing the literature, at least 20 cases with concomitant AUV/D and PUV are reported that are summarized in Table 1.5,20,21,30-39 However, the true number would definitely be more than this because many older reports were not accessible for us and some authors did not focus on this finding in their series. It can be predicted that because of rarity of concomitant AUV/D and PUV compared with conditions like isolated AUV or PUV, many clinicians, especially in tertiary centers, have faced these patients but did not report them in the literature because of the small sample size. For example, in a review article on urethral diverticula, Dorairajan12 has very briefly addressed one of his patients with saccular AUD and concomitant PUV but did not further discuss this finding; this may be one of the first reported cases in the available English literature. The article by Graham et al33 is commonly cited as the first dedicated case report on concomitant AUV/D and PUV. This study reported a child with urinary retention and penoscrotal bulging shortly after birth that was diagnosed with AUD and PUV but interestingly had a totally healthy male twin sibling.33 In an editorial comment on the same article, Dr. King mentioned he also had a patient with congenital urethral obstruction at 2 sites (PUV and coexisting obstructing Cowper cyst).33 One should also consider the obstacles in publishing small series and the reluctance of most journals to publish case reports because of changes in their publication policy that may also affect the authors’ interest in sharing their similar experiences. Signs and Symptoms The presenting symptoms in patients with concomitant AUV/D and PUV vary based on age at diagnosis. The presenting age in the reported cases ranged from antenatal diagnosis (due to hydronephrosis) to 13 years of age (Table 1). The most common presenting symptoms were abnormal urine stream (poor stream, dribbling, and straining); urinary tract infection (UTI); and hydronephrosis. Potentially, any symptoms associated with posterior valves (eg, antenatal or postnatal hydronephrosis, abnormal voiding, failure to thrive, poor feeding, recurrent UTI, urinary ascites, incontinence, urinary retention, and voiding dysfunction)1 or anterior valves (recurrent UTI, 153
154 Table 1. Concomitant anterior urethral valve and/or diverticulum and posterior urethral valve in English literature Source Graham et al
33
Ortiz et al30 Razi et al34 Zia-ul-Miraj35 Rao et al36
Age
Presentation
4d
Penoscrotal mass, urinary retention
NM 18 mo 18 mo 5d
Kajbafzadeh37
3.5 y
Kumar et al5
15 d
Bhagat et al20
8y
Lassaad et al21
2 mo
Narasimhan et al38
14 d
Carvell and Mulik31
3y
Ranawaka and Dickson32 Tran et al39
Kajbafzadeh et al22
Multiple congenital anomalies UTI, scrotal bulging, dribbling Abnormal urinary stream, dysuria, fever Abnormal urinary stream Pyelonephritis, multiple surgeries for VUR, urinary retention Abnormal urinary stream, straining Abnormal urinary stream, straining, recurrent UTI Abnormal urinary stream, straining, UTI Urinary retention
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6d
Abnormal urinary stream, hypertension Abnormal urinary stream, penile bulging Antenatal bilateral HN
3y
Antenatal bilateral HN
2y
Recurrent UTI
3 mo
Antenatal HN
43 d
Urosepsis
2.5 y
Abnormal urinary stream, dribbling
17 d
7y
Incontinence
13 y
Incontinence, UTI
Management Marsupialization of AUD, endoscopic fulguration of PUV NM Open resection of AUD, endoscopic resection of PUV Endoscopic resection of AUD (both anterior and posterior lips) and PUV (4-, 8-, and 12-o’clock positions) Endoscopic fulguration of AUD (distal lip) and PUV (5-, 7-, and 12-o’clock positions) Endoscopic fulguration of both valves
Comment High Cr, bilateral HN Russell-Silver syndrome, hypospadias Right HN, Trab High Cr, bilateral HN, BWT Bilateral HN, BWT
Endoscopic PUV ablation (5-, 7-, 12-o’clock positions), open repair for AUD Endoscopic ablation of PUV and AUV lip incision
Bilateral VUR, previous bilateral ureteral reimplantation, missed diagnosis High Cr, bilateral HN, dilated bladder, left VUR, Trab Bilateral HN, Trab, hypospadias
Endoscopic fulguration of AUV and PUV
BWT
Endoscopic ablation of PUV (5-, 7-, and 12-o’clock positions) and AUV Endoscopic resection of both valves
High Cr, bilateral HN, enlarged bladder, vesicostomy, missed diagnosis High Cr, HN, hypospadias, missed diagnosis
Endoscopic resection of both valves
High Cr, HN, dysplastic kidneys, BWT, hypospadias Left undescended testis, urachal remnant, BWT, Trab, bilateral VUR Bilateral HN, 2-vessel umbilical cord, missed diagnosis High Cr, HN, left VUR, vesicostomy
Endoscopic ablation of AUV (3-, 9-, and 12-o’clock positions) and PUV (5- and 7-o’clock positions) Cold knife resection for both valves Endoscopic resection of AUV (6-o’clock position) and PUV (5-, 7-, and 12-o’clock positions) Endoscopic fulguration of AUV (6-o’clock position) and PUV (5-, 7-, and 12-o’clock positions) Endoscopic fulguration of AUV (6 o’clock) and PUV (5,7,12 o’clock) Endoscopic resection of AUV (6-o’clock position) and PUV (5-, 7-, 12-o’clock positions) Endoscopic resection of AUV (6-o’clock position) and PUV (5-, 7-, and 12-o’clock positions) Endoscopic resection of AUV (6-o’clock position) and PUV (5-, 7-, and 12-o’clock positions)
High Cr, HN, right VUR, Trab, single kidney High Cr, HN, left VUR, Trab, vesicostomy HN, Trab Bilateral VUR, Trab HN, Trab
AUD, anterior urethral diverticulum; AUV, anterior urethral valve; BWT, bladder wall thickness; Cr, creatinine; HN, hydronephrosis; NM, not mentioned; PUV, posterior urethral valve; Trab, bladder trabeculation; UTI, urinary tract infection; VUR, vesicoureteral reflux.
Figure 1. Oblique-view voiding cystourethrography in voiding phase, revealing concomitant anterior and posterior urethral valves. (Color version available online.)
abnormal voiding, incontinence, retention, frequency, dysuria, and bleeding)2 may be present in concomitant AUV/D and PUV. Additionally, in patients with saccular AUD, penile or scrotal bulging during or after urination may signal to the anterior obstruction site. In 1 patient with hypospadias, asymptomatic hypertension diagnosed preoperatively was the sole symptom that led to diagnosis of hydronephrosis and urologic workup.31 The presenting symptoms in children with concomitant AUV/D and PUV may partially depend on the valve that causes more prominent obstructive symptoms. Although AUV and AUD may be associated with serious sequelae on the bladder and the upper urinary tract, it is generally believed that the outcomes are better compared with those of PUV.40 This may be attributed to more distal obstruction and the compliant dilated urethra that partially compensates for the pressure overload. Concomitant AUV/D and PUV may also be associated with hydronephrosis, vesicoureteral reflux, bladder trabeculation and diverticula, and renal damage. Although the limited number of available cases makes the conclusion uncertain, it is intuitive that the outcome in double obstruction may be more under influence of the proximal valve and resemble those seen in PUV patients.22 Diagnosis and Workup Diagnosing concomitant AUV/D and PUV is often the trickiest part. One or even both of the valves may remain unnoticed if inadequate attention is paid to the symptoms and if the physician does not have all the possible diagnoses at the back of the mind. Voiding cystourethrography (VCUG) is the initial study of choice to evaluate the urethra. Anterior urethral dilation proximal to the valve with abrupt narrowing distal to the obstruction site may be seen in AUV. The same pattern in addition to saccular dilation of the urethra is UROLOGY 86 (1), 2015
also evident in AUD. The AUV (specifically when not associated with a large diverticulum) may be easily missed on the initial voiding VCUG because of suboptimal imaging technique with incomplete delineation of the anterior urethra or incomplete visualization of the voiding phase. Full length of the penile urethra should be visualized in the voiding phase of VCUG to detect anomalies of the anterior urethra.41 Alternatively, the anterior anomaly may remain undiagnosed because the posterior valve impedes the adequate flow of urine beyond the proximal obstruction and does not permit bulging of the anterior urethra.5,31 The same phenomenon may impede the anterior flap of AUD to develop completely to cause a valve effect until the proximal obstruction is resolved.36 The valves may also remain unnoticed in retrograde urethrography because they may flatten against the urethral wall and remain open in response to retrograde flow.42 The same may occur during urethrocystoscopy when retrograde flow of fluid is used.42,43 However, a careful urethrocystoscopic evaluation can overcome this diagnostic obstacle by using a manual pressure on the bladder to facilitate urethral dilation during distal urethroscopy.22 Moreover, the surgeon may elevate the valve leaflets using the loop of a resectoscope to facilitate identification of the obstructing structure.22 In urethroscopy, anterior valves may be “cusp-like” with a semilunar leaflet or present as an “irislike” circumferential membrane with a near-central orifice. In cases with AUD, the saccular diverticulum is usually identifiable with an associated defect in the corpus spongiosum. As mentioned previously, the concurrent presence of the valves may be easily missed during the initial workup. In many of the cases, the anterior obstruction site was missed in the initial VCUG and was incidentally diagnosed during urethrocystoscopy for PUV ablation. For example, in a recent report by Tran et al,39 VCUG was performed in an infant with antenatally diagnosed bilateral hydronephrosis and showed a very dilated posterior urethra compatible with PUV but a normal-looking anterior urethra. However, during urethrocystoscopy, a circumferential membrane was encountered in the bulbar urethra and the diagnosis of concomitant AUV and PUV was made.39 In some cases, not only the initial VCUG failed to show AUV/D but also it even remained unnoticed in urethrocystoscopy for PUV ablation. Kumar et al5 reported a 15-day-old boy in whom the anterior urethra was not fully visualized in VCUG and the patient underwent endoscopic PUV ablation. Poor urinary stream after catheter removal and also development of penile bulging led to a second VCUG and diagnosis of AUD in this case.5 Also, in the report by Carvell and Mulik,31 in a 3-year-old boy with diagnosis of PUV, both VCUG and urethrocystoscopy failed to identify the anterior obstruction site; renal function deteriorated after PUV treatment in this child and led to recystoscopy and diagnosis of AUV. In another report, Narasimhan et al38 endoscopically fulgurated PUV in a child with a history of vesicostomy but 155
after occluding the vesicostomy after fulguration, the patient was unable to void and developed a breakthrough UTI; a second VCUG and recystoscopy was needed to diagnose and treat AUV in this case. Similar stories also happened in other cases with concomitant AUV/D and PUV that led to delayed diagnosis, poor response to treatment, more invasive approaches, and repeated diagnostic studies and operations.30,37,39 Taken together, these reports indicate that one or both obstruction sites may remain overlooked in the initial VCUG or urethrocystoscopy and the possibility of another valve should be kept in mind especially when the response to treatment is minimal or not as expected. A high-quality oblique-view VCUG with full delineation of both anterior and posterior urethra during the voiding phase is paramount in diagnosing the urethral anomalies (Fig. 1). Careful urethrocystoscopy using appropriate-sized instruments should be considered if urethral anomalies are suspected during the workup, and special attention should be paid to visualize the full urethral length searching for sites of obstruction. Treatment Regardless of the terminology used, what matters in case of urethral valves are the sequelae of obstruction, and the first goal of treatment is obstruction release. With the advent of advanced small-sized endoscopic instruments, transurethral valve ablation is the procedure of choice for both anterior and posterior valves. This can be achieved via fulguration using Bugbee electrodes, resection of valves using resectoscopes, or ablation using neodymium:yttriumaluminum-garnet laser. Use of blind approaches like valvotomes, Fogarty, or balloon catheters is not recommended because of a higher chance of complications and because miniaturized urethrocystoscopes are now readily available in referral centers. Most experts ablate the posterior valves at 5-, 7-, and 12-o’clock positions. The same applies to circular “iris-like” anterior valves. Anterior obstructing lips of AUD or “cusp-like” AUVs may be ablated at the 6-o’clock position with satisfactory outcomes. Urinary diversion or vesicostomy is reserved for difficult cases with intractable urosepsis, failed treatment, and when appropriate-sized pediatric urology instruments are not available. When a large AUD with considerable corpus spongiosum defect is present, open urethral reconstruction may be needed for satisfactory repair of the defect.
CONCLUSION Concomitant AUV/D and PUV is a complex congenital anomaly challenging our current knowledge on external urogenital tract embryology. An oblique-view VCUG with full delineation of the urethra and also a careful urethrocystoscopy are paramount for a timely and accurate diagnosis. Because the valves may be easily missed on the initial diagnosis, a high degree of suspicion is required and the diagnosis should be kept in mind as eloquently 156
phrased by Graham: “although a patient may present with one type of defect, it is incumbent upon the physician to evaluate completely the urinary tract.”33 Acknowledgment. The authors are greatly thankful to Dr. Afshan Najafi for providing access to required articles in older journals and also her kind contribution during preparation of this article. References 1. Nasir AA, Ameh EA, Abdur-Rahman LO, et al. Posterior urethral valve. World J Pediatr. 2011;7:205-216. 2. Paulhac P, Fourcade L, Lesaux N, et al. Anterior urethral valves and diverticula. BJU Int. 2003;92:506-509. 3. Enriquez G, Garcia-Pena P, Lucaya J, et al. Congenital diverticuli of the anterior urethra. Ann Radiol (Paris). 1978;21:207-214. 4. Kirks DR, Grossman H. Congenital saccular anterior urethral diverticulum. Radiology. 1981;140:367-372. 5. Kumar A, Bajpai M, Gupta AK. Double urethral obstruction in a neonate—a case report. Eur J Pediatr Surg. 2005;15:449-451. 6. Gingell JC, Mitchell JP, Roberts M. Concealed anterior urethral diverticulum causing urinary obstruction in the male child. Br J Urol. 1972;44:602-606. 7. Prakash J, Dalela D, Goel A, et al. Congenital anterior urethral valve with or without diverticulum: a single-centre experience. J Pediatr Urol. 2013;9:1183-1187. 8. Singh DV, Taneja R. Anterior urethral valves without diverticulae: a report of two cases and a review of the literature. Congenit Anom (Kyoto). 2014;54:120-122. 9. Firlit RS, Firlit CF, King LR. Obstructing anterior urethral valves in children. J Urol. 1978;119:819-821. 10. Brueziere J, Guerrieri M. Congenital diverticula and valves of the anterior urethra. Ann Urol (Paris). 1985;19:101-107. 11. Karnak I, Senocak ME, Buyukpamukcu N, et al. Rare congenital abnormalities of the anterior urethra. Pediatr Surg Int. 1997;12:407-409. 12. Dorairajan T. Defects of spongy tissue and congenital diverticula of the penile urethra. Aust New Zealand J Surg. 1963;32:209-214. 13. Stephens FD, Smith ED, Hutson JM. Congenital Anomalies of the Urinary and Genital Tracts. Oxford: Isis Medical Media; 1996:117-133. 14. Williams DI, Retik AB. Congenital valves and diverticula of the anterior urethra. Br J Urol. 1969;41:228-234. 15. McLellan DL, Gaston MV, Diamond DA, et al. Anterior urethral valves and diverticula in children: a result of ruptured Cowper’s duct cyst? BJU Int. 2004;94:375-378. 16. Blaschko SD, Cunha GR, Baskin LS. Molecular mechanisms of external genitalia development. Differentiation. 2012;84:261-268. 17. Stephens FD. Urethral obstruction in childhood; the use of urethrography in diagnosis. Aust N Z J Surg. 1955;25:89-109. 18. Kurzrock EA, Baskin LS, Cunha GR. Ontogeny of the male urethra: theory of endodermal differentiation. Differentiation. 1999;64:115-122. 19. Krishnan A, de Souza A, Konijeti R, et al. The anatomy and embryology of posterior urethral valves. J Urol. 2006;175:1214-1220. 20. Bhagat SK, Gopalakrishnan G, Kekre NS, et al. Anterior and posterior urethral valves with subcoronal hypospadias: a rare association. J Pediatr Surg. 2008;43:e23-25. 21. Lassaad S, Rachida L, Manel BS, et al. Anterior and posterior urethral valves: a rare association. Open J Pediatr. 2011;1:34-36. 22. Kajbafzadeh A, Hosseini Sharifi SH, Keihani S, et al. Concomitant anterior and posterior urethral valves in pediatrics: a single center experience over 12 years and long-term follow-up after endoscopic treatment. Int J Urol. 2015. http://dx.doi.org/10.1111/iju.12712. 23. Krueger RP, Churchill BM. Megalourethra with posterior urethral valves. Urology. 1981;18:279-281. 24. Rajendran R, Sasikumar K, Varma RR. Megalourethra. Indian Pediatr. 1995;32:119-122. 25. Sharma AK, Kothari SK, Goel D, et al. Megalourethra with posterior urethral valves. Pediatr Surg Int. 1999;15:591-592.
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26. Obrinsky W. Agenesis of abdominal muscles with associated malformation of the genitourinary tract: a clinical syndrome. Am J Dis Child. 1949;77:362-373. 27. Boissonnat P, Duhamel B. Congenital diverticulum of the anterior urethra associated with aplasia of the abdominal muscles in a male infant. Br J Urol. 1962;34:59-69. 28. Brueziere J, Demont P. 2 cases of sacciform diverticulum of the anterior urethra in infants. J Urol Nephrol (Paris). 1971;77:772-778. 29. Sellers BB Jr, McNeal R, Smith RV, et al. Congenital megalourethra associated with prune belly syndrome. J Urol. 1976;116: 814-815. 30. Ortiz C, Cleveland RH, Jaramillo D, et al. Urethral valves in Russell-Silver syndrome. J Pediatr. 1991;119:776-778. 31. Carvell J, Mulik R. A case of hypospadias, anterior and posterior urethral valves. J Surg Case Rep. 2013;2013:e1-3. 32. Ranawaka R, Dickson AP. Multiple urethral anomalies: anterior urethral diverticulum, posterior urethral valves, and distal hypospadias. J Pediatr Surg. 2013;48:e5-e8. 33. Graham SD Jr, Krueger RP, Glenn JF. Anterior urethral diverticulum associated with posterior urethral valves. J Urol. 1982;128: 376-378. 34. Razi A, Zargoushi J, Mohammadi D. Anterior urethral valve associated with posterior urethral valve. Med J Islam Repub Iran. 1996; 10:257-258.
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35. Zia-ul-Miraj M. Anterior urethral diverticulum and posterior urethral valves: a rare association. BJU Int. 2000;85:557-558. 36. Rao KL, Eradi B, Menon P. Anterior and posterior urethral valves: a rare association. J Pediatr Surg. 2003;38:E23-E24. 37. Kajbafzadeh AM, Jangouk P, Ahmadi Yazdi C. Anterior urethral valve associated with posterior urethral valves. J Pediatr Urol. 2005; 1:433-435. 38. Narasimhan K, Chua J, Rai R, et al. Missed double urethral obstruction. BJU Int. Published online: 2012; Accessed October 2014; http://dx.doi.org/10.1002/BJUIw-2012-026-web. 39. Tran CN, Reichard CA, McMahon D, et al. Anterior urethral valve associated with posterior urethral valves: report of 2 cases and review of the literature. Urology. 2014;84:469-471. 40. Routh JC, McGee SM, Ashley RA, et al. Predicting renal outcomes in children with anterior urethral valves: a systematic review. J Urol. 2010;184(4 Suppl):1615-1619. 41. Kajbafzadeh A. Congenital urethral anomalies in boys. Part II. Urol J. 2005;2:125-131. 42. Kajbafzadeh AM, Payabvash S, Karimian G. Urodynamic changes in patients with anterior urethral valves: before and after endoscopic valve ablation. J Pediatr Urol. 2007;3:295-300. 43. Kibar Y, Coban H, Irkilata HC, et al. Anterior urethral valves: an uncommon cause of obstructive uropathy in children. J Pediatr Urol. 2007;3:350-353.
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P
osterior urethral valves (PUVs), with an incidence of 1 in 5000 to 8000 male births, are the most common cause of congenital lower urinary tract obstruction.1 Less commonly encountered are obstructive anomalies of the anterior urethra with anterior urethral valves (AUV) and/or diverticula (AUV/D) at the top of the list. Although 10-30 times less prevalent than PUV, these conditions may be similarly devastating and need prompt diagnosis and treatment in early stages.2 A more challenging but less known phenomenon is double urethral obstruction by concomitant anterior and posterior valves. A deeper view on concurrent presence of these conditions may shed some light on the largely unknown etiology and embryology of both AUV/D and PUV. However, our understanding of concomitant AUV/D and PUV is limited to few case reports, and little is known about the presentation, diagnosis, and management of these patients. This limited knowledge together with the assumed rarity of this condition, at least in the published literature, may lead to underdiagnosing of concomitant AUV/D and PUV in children. We hereby review the literature on concomitant AUV/D and PUV to summarize the clinical presentation, diagnosis, and treatment of this condition with a focus on pitfalls in initial workup. We also review some of the embryologic explanations behind AUV, anterior urethral diverticulum (AUD), and PUV in an attempt to explain the concurrence of these conditions based on the current evidence.
Financial Disclosure: The authors declare that they have no relevant financial interests. From the Pediatric Urology Research Center, Children’s Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran Address correspondence to: Abdol-Mohammad Kajbafzadeh, M.D., Pediatric Urology Research Center, Children’s Hospital Medical Center, Pediatric Center of Excellence, No. 62, Dr Gharib Street, Keshavarz Boulevard, Tehran 1419733151, Iran. E-mail: [email protected] Submitted: December 27, 2014, accepted (with revisions): February 17, 2015
ª 2015 Elsevier Inc. All Rights Reserved
METHODS We reviewed the literature by searching the MEDLINE (PubMed) electronic database and Google Scholar through November 2014. We used various combinations of text words such as “anterior urethral valve,” “anterior urethral diverticula,” “posterior urethral valve,” “double obstruction,” and “infravesical obstruction” to identify relevant studies. We also used the “related articles” function in MEDLINE to find related studies. Articles were screened based on titles and abstracts, and relevant articles were selected for a full review. The reference list of related articles was also screened to find additional articles. Online-only articles or those not indexed in MEDLINE were also included. Non-English publications were excluded, unless an informative abstract was provided in English.
ANTERIOR URETHRAL VALVE VS ANTERIOR URETHRAL DIVERTICULUM Which came first, AUV or AUD? Little consensus exists on the use of AUV and AUD terminology in the literature that leads to remarkable inconsistency in different reports. One theory attempts to explain this controversial subject by proposing that a spongy defect in urethra leads to formation of AUD, and the anterior lip sometimes acts as a valve when the diverticulum is filled.3-5 This would also explain the situations that AUD is present without any valve effect. However, another theory sees AUV as the initial insult causing obstruction and turbulence in the proximal urethra leading to urethral bulging and diverticulum formation.6 This theory would better account for AUVs without a diverticulum.7,8 It can be suggested that an early obstructive AUV may affect the normal differentiation of proximal spongy tissues and explain the hallmark defects seen in AUD. A dilated or ruptured Cowper cyst should be differentiated with AUV and AUD, although this condition may share some of the characteristics of AUD and an early obstructive insult may be the underlying cause for its dilation. http://dx.doi.org/10.1016/j.urology.2015.02.019 0090-4295/15
151
In 1978, Firlit et al9 provided a classification for AUV that categorized diverticula as a subtype of AUV with the same pathology. In this classification, type 1 roughly represents AUV without diverticula and AUV types 2-4 represent AUD with or without changes in the upper tract.9 The classification however does not cover AUVs that cause upper tract anomalies in absence of an AUD.8 However, some other authors clearly differentiate between AUV and AUD and believe that these are distinct entities.10,11 As proponents of this theory, Brueziere and Guerrieri10 presented their clinical and surgical experience in 14 cases and concluded that AUD develops outside of the corpus spongiosum and should be treated by open surgical repair, whereas in AUV, the distention is covered by corpus spongiosum and should be treated endoscopically. However, what the authors referred to as “outside of corpus spongiosum” may simply represent incomplete spongy tissue formation with fibrotic and rudimentary remnants similar to pathologic findings of Dorairajan.12 Considering these inconsistencies, we used AUV/D terminology in this review to represent AUV and/or AUD, unless otherwise specified. AUD represents a ventral saccular dilation of the urethra with defects in the corpus spongiosum as its hallmark. The size of the diverticulum is variable based on the degree of tissue defect and probably duration of obstruction and pressure overload on the adjacent tissues. In pathology, a thin epithelial lining covers the diverticulum that is surrounded by a fibrotic and rudimentary spongy tissue.12 The proximal corpus spongiosum may also show degrees of abnormality and fibrosis.12 The distal lip of AUD may act as a “flap-valve” or have a “gate-effect” obstructing the urine flow during urination.13 This probably happens when the diverticulum fills with urine and the pressure on the distal flap pushes it against the urethral roof to occlude the urethra.2,14,15 AUV, if not associated with AUD, mostly represents a “cusp-like” or “iris-like” mucosal remnant in the ventral aspect of the urethra, with no or minimal bulging proximal to it. However, one can argue at what level of dilation a proximal bulging fulfills the criteria to be called a diverticulum, if presence of a spongy defect is not evident or assessable. These anomalies occur anywhere in the anterior urethra, most commonly at the penoscrotal junction and also the penile or bulbar urethra.
EMBRYOLOGY Normal Development of External Genitalia in Male Despite the recent advances in molecular aspects of embryology, our knowledge about the exact mechanisms in the development of urogenital tract is still limited. Complex interactions between androgen-independent, androgen-dependent, and hormonal and environmental factors play a role in external genitalia differentiation.16 During early ambisexual (indifferent) phases, urorectal septum develops toward the cloacal membrane, urogenital and labioscrotal folds appear, and the primary perineal 152
body and genital tubercle form mostly in a hormoneindependent manner.16 Under the effect of Y chromosome and androgens, masculine differentiation of external genitalia continues. Urethral plate and mesenchymal phallic tissue abut the genital tubercle and elongate caudally to form the phallus. The urethral plate canalizes to form the urethral groove (from endothelial origin), whereas urogenital folds (from mesothelial origin) migrate medially and meet at the midline to complete the cylindrical structure of the phallus and penile urethra from behind forward. The mesenchymal urogenital folds later differentiate into vascular erectile tissues (corpus spongiosum and corpora cavernosa). The cranial part of urogenital sinus also forms the membranous and prostatic urethra. Early in development, the Wolffian (mesonephric) ducts insert into the cloaca anteriorly as solid structures but soon they undergo canalization and migrate posteriorly and cranially to finally lie at the level of future verumontanum.13 This gradual migration leaves “snailtrack” marks in the urethra toward verumontanum that are absent in total agenesis of Wolffian ducts.13,17 Most caudally, the cells grow to form glans penis, and canalization begins at the summit of glans by ectodermal ingrowth to meet the urethra formed by the urethral plate proximal to fossa navicularis. However, the formation of this part is more controversial and some disputed the ectodermal origin and proposed that the proximal urethral plate is also responsible for formation of the urethra in fossa navicularis by endodermal-mesenchymal interaction and endodermal differentiation.18,19 Embryology of Anterior Urethral Valve and/or Diverticula Several theories are proposed considering embryologic origin of AUV/D. An early transient obstruction in the anterior urethra (eg, stenosis or preputial narrowing) was first proposed by Watts in 1906 (cited in the study by Williams and Retik14). Others also proposed that incomplete closure of urogenital folds or a failed attempt for urethral duplication might be the cause.2,14 In 1886, Kaufman attributed AUD to a junctional obstruction between glandular and penile urethra (cited in Williams and Retik14). Similarly, Stephens in 199313 found obstructed glandular urethra in autopsies of 2 patients with megalourethra and proposed that delayed canalization of glandular urethra might be the main culprit. However, Williams and Retik14 questioned most of these theories and advocated those proposed by Suter and Johnson that congenital dilation of periurethral glands or cysts that open into the ventral urethra is the underlying cause of AUD. Similarly, McLellan et al15 supposed that rupture of Cowper cyst or syringocele leads to AUD formation. Although a promising theory, one should be skeptical that why the glands were prone to dilation in the first place and if any preceding event (eg, a transient obstruction) led to incomplete spongy tissue formation around the gland. Additionally, this theory does not fully explain the valves in more distal parts and also isolated UROLOGY 86 (1), 2015
valves without a diverticulum (type 1 AUV in Firlit classification). Normally, the urogenital folds envelope the bulbar urethra and differentiate into vascular erectile tissues. Incomplete migration of mesenchymal cells to form the ventral spongy tissue may render some parts rudimentary with inadequate support and provide an appealing theory to explain AUD. When differentiation of the urogenital fold into spongy tissue is totally or largely absent, profound saccular dilation of the penile urethra arises known as scaphoid-type megalourethra. When the defect is more extensive and involves one or both corpora cavernosa, fusiform megalourethra evolves. Embryology in Concomitant AUV/D and PUV Many authors consider AUV/D and PUV as clearly distinct conditions with distinct embryologic origins and explain concomitant AUV/D and PUV as a rare coincidence of 2 unrelated congenital anomalies.7,20-22 However, a different approach would be following the Occam’s razor or diagnostic parsimony to explain the embryology of concomitant AUV/D and PUV. This approach may also provide some explanation for concurrent presence of PUV with megalourethra23-25 and to a lesser extent concurrent presence of prune belly syndrome and anterior urethral anomalies.26-29 Taking all these anomalies into consideration, the most reasonable explanations lie in the mesenchymal origin and an early obstructive insult. During embryologic development, the urogenital folds fuse proximally to distally to form the urethra and abut on the glans. Also, the Wolffian ducts course craniomedially to absorb into the verumontanum.13 Incomplete reabsorption of mesenchymal tissue in the anterior urethra and abnormal migratory passage or defective absorption of the Wolffian duct in the posterior urethra during these stages may leave remnants in the length of the urethra acting as valves. Similarly, any delay in this process may cause a transient obstruction and hinder the normal differentiation of proximal tissues and, for example, cause an arrest in normal spongy tissue formation. This is in line with the aforementioned theory on delayed or arrested canalization of glandular urethra causing extensive proximal defects like megalourethra. It can be hypothesized that if the obstruction is severe and early enough, the developmental process of posterior urethra and upper tract may also be affected in a way that the defects persist even after spontaneous resolution of obstructing site. In 1991, Ortiz et al30 also addressed this holistic approach when they observed a child with Russell-Silver syndrome with multiple anomalies including AUD, PUV, and hypospadias. They linked PUV and spongy defects found in AUD and supposed that inadequate or delayed testosterone production may be involved in this process, a theory that received little attention afterward.30 However, the recent reports of concomitant AUV and PUV with hypospadias may further support this theory.20,31,32 UROLOGY 86 (1), 2015
CONCOMITANT AUV/D AND PUV Available Studies From a statistical viewpoint, one may estimate the prevalence of concomitant AUV/D and PUV to be exceedingly rare by multiplying the incidence of AUV/D by that of PUV. However, this calculation method assumes that no biological or clinical relationship exists between the 2 entities that may not be essentially true. Even if we do not consider these anomalies embryologically related and a result of an underlying intrauterine developmental defect, it is well known that when a congenital anomaly of the urinary tract is present, there is a good chance to find other anomalies. In reviewing the literature, at least 20 cases with concomitant AUV/D and PUV are reported that are summarized in Table 1.5,20,21,30-39 However, the true number would definitely be more than this because many older reports were not accessible for us and some authors did not focus on this finding in their series. It can be predicted that because of rarity of concomitant AUV/D and PUV compared with conditions like isolated AUV or PUV, many clinicians, especially in tertiary centers, have faced these patients but did not report them in the literature because of the small sample size. For example, in a review article on urethral diverticula, Dorairajan12 has very briefly addressed one of his patients with saccular AUD and concomitant PUV but did not further discuss this finding; this may be one of the first reported cases in the available English literature. The article by Graham et al33 is commonly cited as the first dedicated case report on concomitant AUV/D and PUV. This study reported a child with urinary retention and penoscrotal bulging shortly after birth that was diagnosed with AUD and PUV but interestingly had a totally healthy male twin sibling.33 In an editorial comment on the same article, Dr. King mentioned he also had a patient with congenital urethral obstruction at 2 sites (PUV and coexisting obstructing Cowper cyst).33 One should also consider the obstacles in publishing small series and the reluctance of most journals to publish case reports because of changes in their publication policy that may also affect the authors’ interest in sharing their similar experiences. Signs and Symptoms The presenting symptoms in patients with concomitant AUV/D and PUV vary based on age at diagnosis. The presenting age in the reported cases ranged from antenatal diagnosis (due to hydronephrosis) to 13 years of age (Table 1). The most common presenting symptoms were abnormal urine stream (poor stream, dribbling, and straining); urinary tract infection (UTI); and hydronephrosis. Potentially, any symptoms associated with posterior valves (eg, antenatal or postnatal hydronephrosis, abnormal voiding, failure to thrive, poor feeding, recurrent UTI, urinary ascites, incontinence, urinary retention, and voiding dysfunction)1 or anterior valves (recurrent UTI, 153
154 Table 1. Concomitant anterior urethral valve and/or diverticulum and posterior urethral valve in English literature Source Graham et al
33
Ortiz et al30 Razi et al34 Zia-ul-Miraj35 Rao et al36
Age
Presentation
4d
Penoscrotal mass, urinary retention
NM 18 mo 18 mo 5d
Kajbafzadeh37
3.5 y
Kumar et al5
15 d
Bhagat et al20
8y
Lassaad et al21
2 mo
Narasimhan et al38
14 d
Carvell and Mulik31
3y
Ranawaka and Dickson32 Tran et al39
Kajbafzadeh et al22
Multiple congenital anomalies UTI, scrotal bulging, dribbling Abnormal urinary stream, dysuria, fever Abnormal urinary stream Pyelonephritis, multiple surgeries for VUR, urinary retention Abnormal urinary stream, straining Abnormal urinary stream, straining, recurrent UTI Abnormal urinary stream, straining, UTI Urinary retention
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6d
Abnormal urinary stream, hypertension Abnormal urinary stream, penile bulging Antenatal bilateral HN
3y
Antenatal bilateral HN
2y
Recurrent UTI
3 mo
Antenatal HN
43 d
Urosepsis
2.5 y
Abnormal urinary stream, dribbling
17 d
7y
Incontinence
13 y
Incontinence, UTI
Management Marsupialization of AUD, endoscopic fulguration of PUV NM Open resection of AUD, endoscopic resection of PUV Endoscopic resection of AUD (both anterior and posterior lips) and PUV (4-, 8-, and 12-o’clock positions) Endoscopic fulguration of AUD (distal lip) and PUV (5-, 7-, and 12-o’clock positions) Endoscopic fulguration of both valves
Comment High Cr, bilateral HN Russell-Silver syndrome, hypospadias Right HN, Trab High Cr, bilateral HN, BWT Bilateral HN, BWT
Endoscopic PUV ablation (5-, 7-, 12-o’clock positions), open repair for AUD Endoscopic ablation of PUV and AUV lip incision
Bilateral VUR, previous bilateral ureteral reimplantation, missed diagnosis High Cr, bilateral HN, dilated bladder, left VUR, Trab Bilateral HN, Trab, hypospadias
Endoscopic fulguration of AUV and PUV
BWT
Endoscopic ablation of PUV (5-, 7-, and 12-o’clock positions) and AUV Endoscopic resection of both valves
High Cr, bilateral HN, enlarged bladder, vesicostomy, missed diagnosis High Cr, HN, hypospadias, missed diagnosis
Endoscopic resection of both valves
High Cr, HN, dysplastic kidneys, BWT, hypospadias Left undescended testis, urachal remnant, BWT, Trab, bilateral VUR Bilateral HN, 2-vessel umbilical cord, missed diagnosis High Cr, HN, left VUR, vesicostomy
Endoscopic ablation of AUV (3-, 9-, and 12-o’clock positions) and PUV (5- and 7-o’clock positions) Cold knife resection for both valves Endoscopic resection of AUV (6-o’clock position) and PUV (5-, 7-, and 12-o’clock positions) Endoscopic fulguration of AUV (6-o’clock position) and PUV (5-, 7-, and 12-o’clock positions) Endoscopic fulguration of AUV (6 o’clock) and PUV (5,7,12 o’clock) Endoscopic resection of AUV (6-o’clock position) and PUV (5-, 7-, 12-o’clock positions) Endoscopic resection of AUV (6-o’clock position) and PUV (5-, 7-, and 12-o’clock positions) Endoscopic resection of AUV (6-o’clock position) and PUV (5-, 7-, and 12-o’clock positions)
High Cr, HN, right VUR, Trab, single kidney High Cr, HN, left VUR, Trab, vesicostomy HN, Trab Bilateral VUR, Trab HN, Trab
AUD, anterior urethral diverticulum; AUV, anterior urethral valve; BWT, bladder wall thickness; Cr, creatinine; HN, hydronephrosis; NM, not mentioned; PUV, posterior urethral valve; Trab, bladder trabeculation; UTI, urinary tract infection; VUR, vesicoureteral reflux.
Figure 1. Oblique-view voiding cystourethrography in voiding phase, revealing concomitant anterior and posterior urethral valves. (Color version available online.)
abnormal voiding, incontinence, retention, frequency, dysuria, and bleeding)2 may be present in concomitant AUV/D and PUV. Additionally, in patients with saccular AUD, penile or scrotal bulging during or after urination may signal to the anterior obstruction site. In 1 patient with hypospadias, asymptomatic hypertension diagnosed preoperatively was the sole symptom that led to diagnosis of hydronephrosis and urologic workup.31 The presenting symptoms in children with concomitant AUV/D and PUV may partially depend on the valve that causes more prominent obstructive symptoms. Although AUV and AUD may be associated with serious sequelae on the bladder and the upper urinary tract, it is generally believed that the outcomes are better compared with those of PUV.40 This may be attributed to more distal obstruction and the compliant dilated urethra that partially compensates for the pressure overload. Concomitant AUV/D and PUV may also be associated with hydronephrosis, vesicoureteral reflux, bladder trabeculation and diverticula, and renal damage. Although the limited number of available cases makes the conclusion uncertain, it is intuitive that the outcome in double obstruction may be more under influence of the proximal valve and resemble those seen in PUV patients.22 Diagnosis and Workup Diagnosing concomitant AUV/D and PUV is often the trickiest part. One or even both of the valves may remain unnoticed if inadequate attention is paid to the symptoms and if the physician does not have all the possible diagnoses at the back of the mind. Voiding cystourethrography (VCUG) is the initial study of choice to evaluate the urethra. Anterior urethral dilation proximal to the valve with abrupt narrowing distal to the obstruction site may be seen in AUV. The same pattern in addition to saccular dilation of the urethra is UROLOGY 86 (1), 2015
also evident in AUD. The AUV (specifically when not associated with a large diverticulum) may be easily missed on the initial voiding VCUG because of suboptimal imaging technique with incomplete delineation of the anterior urethra or incomplete visualization of the voiding phase. Full length of the penile urethra should be visualized in the voiding phase of VCUG to detect anomalies of the anterior urethra.41 Alternatively, the anterior anomaly may remain undiagnosed because the posterior valve impedes the adequate flow of urine beyond the proximal obstruction and does not permit bulging of the anterior urethra.5,31 The same phenomenon may impede the anterior flap of AUD to develop completely to cause a valve effect until the proximal obstruction is resolved.36 The valves may also remain unnoticed in retrograde urethrography because they may flatten against the urethral wall and remain open in response to retrograde flow.42 The same may occur during urethrocystoscopy when retrograde flow of fluid is used.42,43 However, a careful urethrocystoscopic evaluation can overcome this diagnostic obstacle by using a manual pressure on the bladder to facilitate urethral dilation during distal urethroscopy.22 Moreover, the surgeon may elevate the valve leaflets using the loop of a resectoscope to facilitate identification of the obstructing structure.22 In urethroscopy, anterior valves may be “cusp-like” with a semilunar leaflet or present as an “irislike” circumferential membrane with a near-central orifice. In cases with AUD, the saccular diverticulum is usually identifiable with an associated defect in the corpus spongiosum. As mentioned previously, the concurrent presence of the valves may be easily missed during the initial workup. In many of the cases, the anterior obstruction site was missed in the initial VCUG and was incidentally diagnosed during urethrocystoscopy for PUV ablation. For example, in a recent report by Tran et al,39 VCUG was performed in an infant with antenatally diagnosed bilateral hydronephrosis and showed a very dilated posterior urethra compatible with PUV but a normal-looking anterior urethra. However, during urethrocystoscopy, a circumferential membrane was encountered in the bulbar urethra and the diagnosis of concomitant AUV and PUV was made.39 In some cases, not only the initial VCUG failed to show AUV/D but also it even remained unnoticed in urethrocystoscopy for PUV ablation. Kumar et al5 reported a 15-day-old boy in whom the anterior urethra was not fully visualized in VCUG and the patient underwent endoscopic PUV ablation. Poor urinary stream after catheter removal and also development of penile bulging led to a second VCUG and diagnosis of AUD in this case.5 Also, in the report by Carvell and Mulik,31 in a 3-year-old boy with diagnosis of PUV, both VCUG and urethrocystoscopy failed to identify the anterior obstruction site; renal function deteriorated after PUV treatment in this child and led to recystoscopy and diagnosis of AUV. In another report, Narasimhan et al38 endoscopically fulgurated PUV in a child with a history of vesicostomy but 155
after occluding the vesicostomy after fulguration, the patient was unable to void and developed a breakthrough UTI; a second VCUG and recystoscopy was needed to diagnose and treat AUV in this case. Similar stories also happened in other cases with concomitant AUV/D and PUV that led to delayed diagnosis, poor response to treatment, more invasive approaches, and repeated diagnostic studies and operations.30,37,39 Taken together, these reports indicate that one or both obstruction sites may remain overlooked in the initial VCUG or urethrocystoscopy and the possibility of another valve should be kept in mind especially when the response to treatment is minimal or not as expected. A high-quality oblique-view VCUG with full delineation of both anterior and posterior urethra during the voiding phase is paramount in diagnosing the urethral anomalies (Fig. 1). Careful urethrocystoscopy using appropriate-sized instruments should be considered if urethral anomalies are suspected during the workup, and special attention should be paid to visualize the full urethral length searching for sites of obstruction. Treatment Regardless of the terminology used, what matters in case of urethral valves are the sequelae of obstruction, and the first goal of treatment is obstruction release. With the advent of advanced small-sized endoscopic instruments, transurethral valve ablation is the procedure of choice for both anterior and posterior valves. This can be achieved via fulguration using Bugbee electrodes, resection of valves using resectoscopes, or ablation using neodymium:yttriumaluminum-garnet laser. Use of blind approaches like valvotomes, Fogarty, or balloon catheters is not recommended because of a higher chance of complications and because miniaturized urethrocystoscopes are now readily available in referral centers. Most experts ablate the posterior valves at 5-, 7-, and 12-o’clock positions. The same applies to circular “iris-like” anterior valves. Anterior obstructing lips of AUD or “cusp-like” AUVs may be ablated at the 6-o’clock position with satisfactory outcomes. Urinary diversion or vesicostomy is reserved for difficult cases with intractable urosepsis, failed treatment, and when appropriate-sized pediatric urology instruments are not available. When a large AUD with considerable corpus spongiosum defect is present, open urethral reconstruction may be needed for satisfactory repair of the defect.
CONCLUSION Concomitant AUV/D and PUV is a complex congenital anomaly challenging our current knowledge on external urogenital tract embryology. An oblique-view VCUG with full delineation of the urethra and also a careful urethrocystoscopy are paramount for a timely and accurate diagnosis. Because the valves may be easily missed on the initial diagnosis, a high degree of suspicion is required and the diagnosis should be kept in mind as eloquently 156
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