Journal of Pediatric Urology (2011) 7, 632e635
Vesicoureteral reflux in children with urachal anomalies Janelle A. Fox a,*, Shawn M. McGee a, Jonathan C. Routh a, Candace F. Granberg a, Richard A. Ashley a, Joel C. Hutcheson b, David R. Vandersteen b, Yuri E. Reinberg b, Stephen A. Kramer a a b
Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA Children’s Hospital of Minnesota, Minneapolis, MN, USA
Received 24 April 2010; accepted 15 April 2011 Available online 12 May 2011
KEYWORDS Vesicoureteral reflux; Children; Diverticulum; Urachal cyst; Urachus
Abstract Objective: We report the largest known series of vesicoureteral reflux (VUR) in children with urachal anomalies (UA). Methods: Two institutions’ records were reviewed for children with UA (1951‒2007). Results: Of 30 girls and 36 boys with UA (34 urachal cysts, 14 patent urachus, 10 urachal diverticula, 7 urachal sinuses, and 1 unknown), 57 (86%) underwent surgical resection or drainage. A voiding cystourethrogram was obtained in 22 (33%). VUR was demonstrated in 14 of the 22 children (64%), and rates were similar among the various types of UA. The median age with versus without VUR was not different (1.3 vs 1.7 years, P Z 0.97). Of 24 refluxing renal units, classification was grade 3 in 71%, 4‒5 in 12%, and unspecified in 17%. Four children (26%) underwent ureteroneocystostomy and 10 observed patients resolved spontaneously. Conclusion: To our knowledge, this is the first series of VUR associated with UA. The increased incidence of VUR (64%) in this small subset of patients warrants prospective studies to determine if there is a positive correlation with UA. We believe thorough genitourinary and family histories are important when evaluating children with UA to help detect clinically significant VUR. ª 2011 Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company.
Introduction Embryologically, the urachus is the intra-abdominal portion of the fetal allantois, which involutes into a preperitoneal
* Corresponding author. Tel.: þ1 507 284 2511; fax: þ1 507 284 4951. E-mail address: [email protected]
fibrous cord to form the median umbilical remnant in normal development or urachal anomalies (UA) in pathologic development . Microscopically, the median umbilical ligament is surrounded by umbilicovesical fascia, serving to contain pathologic processes within the structure, with three component layers: an inner transitional or cuboidal epithelial layer, a connective tissue covering, and an outer smooth muscle layer contiguous with detrusor fibers. Four distinct UA have been described: patent
1477-5131/$36 ª 2011 Published by Elsevier Ltd on behalf of Journal of Pediatric Urology Company. doi:10.1016/j.jpurol.2011.04.001
Vesicoureteral reflux in children with urachal anomalies urachus (50%), urachal cyst (30%), umbilical-urachal sinus (15%), and vesicourachal diverticulum (3e5%) . UA causing symptoms in childhood also appear to differ prognostically from those identified in adulthood. It is recommended that UA found in childhood be excised to prevent the development of urachal malignancy, which has been described in 51% of patients presenting as adults . While concurrent genitourinary anomalies have been described in children with UA, the true incidence is unknown. Small series of patients have been reported with concurrent non-obstructive genitourinary anomalies discovered during evaluation of symptomatic UA in children. Associations of a patent urachus with prune belly syndrome or posterior urethral valves are well recognized . Symptomatic UA are associated with umbilical drainage, pain, palpable mass, or infection. Ultrasonography is the most common diagnostic modality used  and voiding cystourethrography (VCUG) can be performed to help distinguish the patent urachus from urachal sinus . The use of VCUG for diagnostic assessment or preoperatively has not been recommended routinely [5,6]. However, performance of VCUG provides a unique opportunity to determine the incidence and characteristics of vesicoureteral reflux (VUR) in children with UA, while better defining the UA anatomy.
Methods Following appropriate Institutional Review Board approval, we retrospectively reviewed the records at two academic centers from 1951 to 2007 for patients presenting with UA. Abstracted data included patient demographics, UA type, presence of VUR, and treatment methods. Age is reported as median (range). Statistical analyses were performed using Fisher’s exact test, the Wilcoxon rank-sum test, or the KruskaleWallis test as needed based on data characteristics. All analyses were performed using SAS 9.2 (SAS Institute, Cary, NC, USA). All tests were two-sided and P-values less than or equal to 0.05 were considered statistically significant.
633 undergoing VCUG with and without VUR are outlined in Table 1. Abdominal ultrasound was done in 33% of children (22/66), with 55% (12/22) undergoing concurrent VCUG and renal ultrasound. Among the patients undergoing VCUG without ultrasound, further diagnostic imaging with CT was performed in two. The remaining nine were diagnosed without further imaging using physical exam (2) or intraoperative inspection (7).
Vesicoureteral reflux VUR was demonstrated in 14 of the 22 patients (64%), and was bilateral in 9 of the 14 (64%). Of 24 renal units with VUR, reflux grade was 3 in 71%, 4e5 in 12%, and unspecified in 17%. Four children underwent ureteroneocystostomy (6 renal units) and 10 observed cases resolved their reflux spontaneously. The median age of patients with and without VUR was not significantly different: 1.3 (0.01e17.8) vs 1.7 (0.02e6.5) years, P Z 0.97. Similarly, there was no difference in the incidence of reflux among the urachal anomalies (P Z 0.88). Of the 14 children with VUR, 6 had urachal cysts (43%), 5 had a patent urachus (36%), 3 had urachal diverticula (21%), and none (0%) had a draining sinus. All children with UA who underwent treatment for VUR also underwent treatment for the UA (4/4, 100%); 3 underwent excision of the UA (2 urachal diverticula, 1 urachal cyst) and 1 underwent partial cystectomy for a patent urachus. Nine of 10 patients (90%) in whom VUR was diagnosed and observed on prophylactic antibiotics also underwent treatment for the UA; the 10th patient with a urachal cyst was observed.
Treatment of vesicoureteral reflux Of the four patients undergoing ureteral reimplantation, reflux grade and laterality were as follows (4 patients, 6 renal units): grade 5 bilaterally, grade 5 unilaterally, grade
Table 1 Children undergoing VCUG during work up of urachal anomaly. With VUR
Urachal anomalies We identified 30 girls and 36 boys (66 patients) with UA. In 65 patients, the type of UA could be determined from review of records, including 34 urachal cysts, 14 patent urachus, 10 urachal diverticula, and 7 urachal sinuses, of which 57 (86%) underwent surgical resection or drainage. Median patient age at the time of diagnosis of urachal anomaly was 1.8 (0.01e30.5) years. Age at diagnosis differed significantly between the various types of UA: 0.3 (0.1e18.3) years for sinuses/patent urachus vs 5.4 (0.01e30.5) years for cysts vs 9.1 (7.4e10.8) years for diverticula (P Z 0.03). Male gender was associated with higher likelihood of urachal cysts (52% cysts vs 33% sinuses/patent urachus vs 15% diverticula, P Z 0.35).
Diagnostic imaging A VCUG was obtained in 22 patients (33%) at some point during their work up for UA. Characteristics of children
VCUG performed: 22 (33%)a patients Median age VUR grade (24 renal units) 1e3 4e5 Unspecified Laterality (14 patients) Bilateral Treatment (14 patients) Ureteroneocystostomyc Observation/antibioticsd
Without VUR 7 (36%)
17 (71%) 3 (12%) 4 (17%)
n/a n/a n/a
4 (29%) 10 (71%)
a VCUG performed as part of diagnostic work up of urachal anomaly in 22 of 66 total children. b Of 14 children with VUR, 24 renal units were affected. c In 3 of 4 patients, reflux grade was known. One patient had unspecified grade bilateral VUR. d All observed cases of VUR resolved spontaneously.
J.A. Fox et al.
2 unilaterally with associated hutch diverticulum, and unspecified grade bilaterally. Indication for ureteral reimplantation, type of reimplant, prior antibiotic therapy, functional renal studies and scarring are summarized in Table 2. The remaining 10 patients were observed and reflux resolved in each child. There was no significant difference between observed and treated patients in terms of their age at diagnosis, 0.3 (0.1e10.2) vs 10.8 (0.01e17.8) years (P Z 0.14), although it did appear there was a trend toward younger age at diagnosis. Infantile presentation of UA was common with 28 of 66 (42%) children diagnosed before age 1 year. Similarly, 6 of 14 children (43%) with VUR and UA were diagnosed before age 1 year.
Discussion Utility of VCUG This study was undertaken to address the incidence of VUR in children with UA. We recognize potential detection bias in that reasoning for a VCUG was not always specified. Family history of VUR, presence of hydronephrosis on abdominal ultrasound, or associated medical comorbidities and/or birth defects may have introduced an inherent bias in the work up of the children who underwent VCUG. Overall, the incidence of VUR in children with all types of UA was 64%. This high incidence raises the question of whether VUR screening would be useful in children diagnosed with UA. This study cannot positively answer this question due to its retrospective nature, but prospective studies may do so. Given the high yield for detection of VUR when VCUG was performed, we encourage the consideration of renal ultrasound and VCUG when a child is felt to be ‘at-risk’ (e.g. positive family history, previous febrile urinary tract infection (UTI), renal anomalies, prenatal hydronephrosis). Ultrasound was the most common initial diagnostic radiographic modality used (33% of all patients). However, VCUG is still the preferred study for distinguishing a sinus versus patent urachus (33% of all patients underwent VCUG). If VUR is found, pediatric urologic referral prior to UA intervention is warranted. Limited VCUG usage in the work up of UA may be missing more cases of VUR. Unfortunately, we cannot determine from this study whether patients with UA can be more selectively screened based on known risk factors for VUR, such as family history, associated birth defects, and presence of hydronephrosis. Future studies will be needed to investigate whether there truly is
a positive association of VUR with UA, and whether routine renal ultrasound and VCUG have a positive health impact with prevention of pyelonephritis or renal scarring.
Incidence and significance of VUR VUR is well documented to occur more frequently in infants with UTI; however, we identified reflux in 64% children with UA. This is much higher than isolated VUR rates of 30% with UTI and 1% in the general population [7,8], but the clinical significance of VUR in children with UA is not entirely known. There is no relevant literature to determine whether the pathogenesis of VUR is different, such as whether the UA predisposes a child to develop reflux or vice versa. Age at presentation may play a role in our high incidence of VUR, as 43% of all refluxing patients with UA were diagnosed before age 1 year. Observed patients with VUR did not experience recurrent UTIs, and infected urine in the context of symptomatic UA was also rare. Only two patients had UTIs at the time of UA treatment. One can therefore argue that VCUG in children presenting with UA (without febrile UTI) is more commonly detecting clinically insignificant, physiologic reflux that the child is destined to outgrow. Many animal species are born with physiologic VUR, which resolves during growth without any known added health risk, but the exceptionally high incidence (64%) of VUR remains concerning [9,10]. In addition, not all patients had ‘benign’ reflux. Four patients were surgically managed although two of these appeared to have concurrent bladder dysfunction (posterior urethral valves, neurogenic bladder) which carried an inherent risk for VUR. Management of the two patients with bladder dysfunction may have been different in the current era, with surgical intervention less common than at the time of their diagnosis in 1987 and 1991. Renal scarring prompted two of the four ureteroneocystostomies and one was deemed to have failed antibiotics with recurrent febrile UTIs (Table 2). Theoretically, an infected UA with communication to the urinary tract might increase the risk of febrile UTI and scarring, if VUR is undiagnosed and the child is not on prophylactic antibiotics. Perhaps surgical excision of an infected UA may reduce this risk, as the majority of children (13/14) with VUR eventually required surgical treatment of the urachal lesion. In addition, most UA did not present with infection (only 3 of our 66 patients presented with UTI or cellulitis) so it seems unlikely that presence of a UA adversely affects the outcome of a patient’s VUR.
Summary of clinical information for patients undergoing both ureteral reimplantation and treatment of UA.
Type of UA?
Radiographic renal scar?
7 months 1 year 10 years 17 years
M F M M
Grade 5/Bilateral Unspecified/Bilateral Grade 5/Left Grade 2 with hutch diverticulum/Right
No NGB PUV No
Patent urachus Cyst Diverticulum Diverticulum
No No Yes Yes
Yes Unknown No No
7 months Unknown 1 year Unknown
NGB Z neurogenic bladder; PUV Z posterior urethral valves.
Vesicoureteral reflux in children with urachal anomalies
Possible etiology of concurrent VUR Bladder outlet obstruction, which is found in up to14% of patent urachus cases [11,12], may also contribute via a pop-off mechanism to development of VUR. However, this would not account for all cases. Other anomalies of the genitourinary tract, such as solitary kidney, renal duplication, renal ectopia, and hutch bladder diverticulum, are associated with increased risk of VUR. UA may be in this associated spectrum. In theory, any abnormality in the normal development of the ureterotrigonal complex could result in lateral displacement of the ureteral orifice or poor detrusor support. Normal embryologic development of the genitourinary tract describes mesenchymal differentiation into detrusor muscle throughout the bladder with closure of the urachus by 16 weeks’ gestation . Thus, one possibility for an association between UA and VUR is abnormal mesenchymal development during the fetal period. Patent urachus is a described anomaly in Eagle-Barrett syndrome, which is a well recognized failure of mesodermal development. More commonly, urachal anomalies are thought to arise from delayed closure of the urachus. If a persistent urachal anomaly alters the vertical configuration or normal lie of the bladder (i.e. anchors the bladder more superiorly), it is reasonable to theorize the ureteric bud may join the bladder in an aberrant location.
Antibiotic prophylaxis and follow-up recommendations Routine antibiotic prophylaxis is recommended for patients with VUR electing surveillance. In low-risk patients without renal scarring, breakthrough febrile UTIs, or unfavorable anatomy, routine surveillance on antibiotics is feasible with high resolution rates. In this series, 71% (10/14) refluxing children resolved their VUR on antibiotic prophylaxis alone but 29% (4/14) required surgical correction. Patients with surgically treated VUR were older, or had more complex anatomy and higher grades of reflux. Half the surgically treated patients in this series also developed renal scarring or recurrent febrile UTIs as an indication for surgery.
Conclusions The high incidence of VUR in children with UA is noteworthy and has not been previously reported. It also did not classically present with febrile UTI, bringing into question the clinical significance of VUR in this study. Despite the high incidence of VUR, only a few patients required surgical intervention and a majority spontaneously resolved their reflux. Making the diagnosis of VUR at the time of UA evaluation may afford a unique opportunity to prevent renal scarring from an initial UTI, or to avoid a second surgery if already undergoing operative repair of the UA.
635 For these reasons we feel thorough genitourinary and family histories should be obtained during the evaluation of children with UA for consideration of renal ultrasound and VCUG in at-risk patients. Future prospective studies are needed to determine if the higher incidence of VUR in children with UA is accurate and clinically significant.
Conflict of interest statement The authors have no conflicts of interest to disclose.
Acknowledgments The authors have no financial disclosures.
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