Ureteral Duplication, Ureteral Ectopia, and Ureterocele

Ureteral embryology is fundamental in understanding abnormal development of the ureter. Ureteral development begins as early as 4 weeks' gestation. The ureteral bud branches off of the mesonephric (or wolffian) duct and eventually extends into the nephrogenic blastema, an area of undifferentiated mesenchyma. The ureteral bud is responsible for the formation of the entire renal collecting system, from the ureteral orifice to the collecting ducts of the kidney.

At the distal aspect of the ureteral bud, the mesonephric duct is incorporated into the developing bladder, and the ureteral orifice is superolaterally carried to its normal position on the trigone. The more distal segment of the mesonephric duct is carried inferomedially and is incorporated into the bladder neck. In the male fetus, it also develops into the seminal vesicle, vas deferens, and epididymis. In females, it becomes the Gartner duct, which is located between the vagina and urethra.

In cases of ureteral duplication where the ureteral bud arises twice, the lower-pole ureter integrates with the bladder earlier than expected and, as a result, is carried into a more superolateral position. Thus, the distal ureter is poorly supported by the trigone and has a shorter intramural tunnel, both of which situations increase the likelihood of VUR.

The upper-pole ureter then integrates with the bladder later than usual and is carried inferomedially. This may result in a ureteral orifice that is low on the trigone or is ectopically located at the bladder neck, ejaculatory duct, seminal vesicle, or vas deferens in males.

In females, the ureter may end in a Gartner duct, which can eventually erode into the nearby vagina or the urethra, inferior to the urinary sphincter. This may be the cause of continuous urinary incontinence in females. In boys, all of the wolffian structures are located above the external urinary sphincter, and incontinence does not occur.

Ureteral ectopia can occur without duplication and is believed to result from the delayed incorporation of the distal ureter into the developing bladder, as described above.

The embryology of the ureterocele is debatable. Some believe that failure of the Chwalla membrane to break down at the distal ureter during development results in obstruction and saccular dilation. Others argue that aberrant signaling from the expanding urogenital sinus results in dilation of the distal ureter.

United States statistics

In autopsy series, the incidence of ureteral duplication is estimated at slightly less than 1%. In studies of young children with UTIs, the incidence of duplication rises to 8%.

The incidence of ureteroceles has been reported to be in the range of 1 per 5000-12,000 population. Approximately 10% are bilateral, 60-80% are ectopic, and 80% are associated with an upper-pole ureter of a duplex kidney. Single-system ectopic ureteroceles are rare, usually occur in males, and may be associated, in rare cases, with cardiac and genital anomalies. When ureteroceles arise from the upper pole of a duplicated kidney, the upper pole is frequently dysplastic.

Age-related demographics

Antenatally, ureteral duplication is commonly suggested by hydronephrosis when the upper-pole ureter is associated with obstruction or when the lower pole is associated with high-grade reflux. The duplication may present in early childhood or later in life, when UTI prompts evaluation.

Antenatally, ureteral ectopia is commonly detected when hydronephrosis is present because of obstruction. Ectopic ureters that enter below the urethral sphincter present at school age or later in girls who have failed to toilet train or who have had continuous drip incontinence.

Antenatally, ureteroceles are most commonly diagnosed when associated with hydronephrosis or in childhood when associated with UTI. When found in adults, they are usually intravesical, are associated with a single collecting system, are less likely to alter the function of the involved kidney, and may not be of clinical concern.

Sex-related demographics

Ureteral duplication, ectopia, and ureteroceles are all more common in females. This may reflect the higher likelihood of UTIs in females, resulting in subsequent detection of the duplication.

Race-related demographics

Ureteroceles are more common in whites than in blacks.

Ureteral duplication and ectopic and nonectopic ureterocele tend to present early in life, even prenatally.

Antenatal presentation

Antenatal maternal ultrasonography (US) has led to earlier and increased detection of ureteral abnormalities. Hydronephrosis that is identified antenatally warrants postnatal follow-up imaging.

Neonatal presentation

Urinary tract infection (UTI) in the first few months of life remains the most common presentation. An infected obstructed system may lead to life-threatening urosepsis. Infants may also exhibit failure to thrive or nonspecific gastrointestinal (GI) symptoms.

Older childhood presentation

UTI is a common presentation at any age. Ureteral duplication and ectopic ureters can be associated with both reflux and obstruction, predisposing to UTI. Hematuria or pain in the abdomen or flank may also occur.

Ureteral ectopia in females can present as continuous drip incontinence in cases in which the ureteral orifice is located in the vagina, septum, or the urethra, below the sphincter mechanism. Persistently damp underwear (day and night) is a typical history finding.

Girls can present with prolapse of the ureterocele through the urethra, which may lead to bladder outlet obstruction or incontinence. This is the most common cause of urethral obstruction in girls.[1] Ureteroceles may be seen upon careful physical examination of the genitalia.

Ureteroceles in boys may prolapse and occasionally obstruct the urethra, but this is very rare.

A hydronephrotic kidney is the most common palpable abdominal mass in the newborn and suggests an obstructed kidney, possibly resulting from an ectopic ureter or ureterocele.

Occasionally, urine that drips from the meatus of an ectopic ureter at the urethrovaginal septum can be detected. Close inspection of the genitalia in a female with urinary retention may reveal a prolapsing ureterocele. (See the images below.)

Rarely, bilateral renal dysplasia or significant renal scarring may be present, resulting in impaired renal function. In this scenario, renal function and electrolyte levels must be monitored. These patients must also be assessed for hypertension.

Antenatal fetal ultrasonography (US) is often the initial study suggesting the diagnosis on the basis of hydroureteronephrosis. The natural history of antenatally diagnosed duplication anomalies is that approximately half of these infants develop urinary tract infection (UTI), and about 25% require surgical intervention in the first few years of life.[2]

Postnatal abdominal US is the best initial screening study.

Renal measurements in duplicated collecting systems are often longer than those of a contralateral nonduplicated system (see the image below).

Disparate hydronephrosis in the upper and lower pole of a kidney suggests ureteral duplication, especially with upper-pole dilation associated with an obstructed or ectopic ureter or with a ureterocele. (See the image below.)

A ureterocele can usually be seen at the bladder level and appears as a well-defined cystic intravesical mass that can be proximally followed into a dilated ureter (see the inage below). If the bladder is decompressed, visualization of a ureterocele is more difficult.

US provides imaging for gross evaluation of the renal parenchyma. Increased echogenicity and renal cysts are sonographic signs that suggest renal dysplasia.

Virtual sonographic cystoscopy appears promising as a noninvasive means of evaluating ectopic ureterocele in children.[3]

Intravenous pyelography (IVP) is not commonly used. It generally reveals duplicated collecting systems and their level of confluence. In young girls with persistent incontinence, IVP may be helpful in defining ureteral anatomy and the level at which an ectopic ureter may be found. Typically, a ureterocele has been described as having a "cobra head" or "spring onion" configuration at the bladder level. Stones that collect in the ureterocele (see the image below) may be visible on the scout film.

Because duplicated systems generally have poorly functioning renal moieties associated with ectopia or ureteroceles, these distinct images are usually observed with single-system intravesical ureteroceles. Delayed images are helpful in identifying poorly functioning renal units.

Retrograde pyelography (see the image below) can define the ureteral anatomy, and puncture of the ureterocele with instillation of contrast may aid in defining the origin of the lesion.

Duplicated collecting systems with lower-pole reflux can be visualized by means of voiding cystourethrography (VCUG). The configuration of the kidney lacks opacification of the nonrefluxing upper pole, giving it the appearance of a "drooping lily" (see the image below).

Ectopic ureters generally do not reflux unless they are ectopic to the bladder neck. In this case, the refluxing unit opacifies only during voiding, when the bladder neck is open. Occasionally, the radiologist may inadvertently pass a catheter transurethrally up the ectopic ureter. The initial films then opacify only that collecting system and not the bladder.

Ureteroceles are best imaged at initial filling and appear as a filling defect in the bladder base (see the image below). Identifying which side large ureteroceles are associated with can be difficult. Reflux of the ipsilateral lower pole is observed in approximately 50% of cases. Contralateral reflux may be observed in 25% of cases, and reflux into the ureterocele may be observed in 10% of cases.

Mercaptotriglycylglycine (MAG-3) renal scintigraphy is the renal scan most commonly obtained to evaluate relative renal function and drainage. It provides information on segmental renal function, allowing comparison of the upper-pole moiety to the lower-pole moiety (see the image below). It may aid in the determination of salvageability and selection of operative technique. MAG-3 furosemide renography may also quantitate the degree of obstruction in moieties with preserved function.

Technetium-99m (99mTc) diethylenetriaminepentaacetic acid (DTPA) is similar to MAG-3 but is less efficacious in patients who have kidneys with poor function and in newborns because of their relatively impaired glomerular filtration rates. Radiation exposure is fairly high with this compound.

99mTc dimercaptosuccinic acid (DMSA) is an agent that is taken up by the renal tubular cells and is used for renal scintigraphy.[4]  DMSA resting can be used reliably to assess renal function but is not useful in evaluating urinary drainage of the upper urinary tract because it is secreted slowly into the urine.

Axial imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is rarely the initial study of choice. In one study, contrast CT was the most reliable study in demonstrating the poorly functioning upper-pole renal moiety and the associated ectopic ureter causing continuous drip incontinence.[5]

Gadolinium-enhanced MRI may be valuable in opacifying an ectopic ureter that causes incontinence in a female, whereas other studies may not be diagnostic. A retrospective study by Ji et al suggested that antenatal MRI can be effective for diagnosing fetal duplex kidney deformity and associated ureteral and other abnormalities.[6]

Although sometimes used as an investigative modality, cystoscopy is usually performed during surgical intervention to verify the diagnosis. (See the image below.)

The search for the orifice of an ectopic ureter may be extremely difficult. Tedious probing of any small dimple along the urethra or anterior vaginal wall with a whistle-tip catheter may be rewarded with visual confirmation of the offending moiety upon the retrograde injection of contrast. The use of indigo carmine or methylene blue injected intravenously may help in locating an ectopic ureteral orifice at the time of cystoscopy.

Findings with large or ectopic ureteroceles, which can distort and obscure the entire field of vision, can be confusing. Finding the ureterocele orifice may be challenging.

Small ureteroceles may not be evident, especially when the bladder is distended, which causes the ureterocele to flatten or evert. When associated with duplication, large ureteroceles may obscure visualization of any ipsilateral ureteral orifice.

Antibiotic suppression is usually warranted in newborns with hydronephrosis or in patients who present with urinary tract infection (UTI) until the diagnosis is made and reflux is ruled out. For vesicoureteral reflux (VUR), antibiotics are generally continued until the reflux spontaneously resolves or is surgically treated or until the patient is toilet-trained and has a considerable infection-free interval. Antibiotic prophylaxis is often continued in patients with obstructed systems and in infants with dilated nonobstructed systems.

Early consultation, even antenatally, with a pediatric urologist is suggested in all cases.

Various surgical options are available to treat ureteral duplication, especially with ureteral ectopia or ureterocele. In a survey of urologists, little consistency was found in the management strategy for ureteroceles, emphasizing that care must be individualized.[7]

There has been a trend toward managing ureteroceles more conservatively with expectant or minimally invasive therapies rather than with major reconstructive efforts.[8, 9]  The decision to treat ureteral duplication surgically requires the consideration of multiple elements (see below).

Factors affecting decision for surgical treatment

Age of patient

Duplicated collecting systems with reflux are expectantly managed with antibiotic suppression until the reflux spontaneously resolves or until the child is older (6-12 months), at which time surgery may be more easily accomplished.

In infants, the small bladder can limit surgical reconstruction with regard to creating a ureteral tunnel that is long enough to prevent recurrent reflux. Ureteral reimplants in small infants with breakthrough infections are possible but can be difficult and are associated with increased complications and failures.

In infants with duplicated systems and a well-functioning but obstructed upper-pole moiety or an obstructed ectopic single-system ureter, urinary diversion may be the treatment of choice until the bladder is bigger and a ureteral reimplant with or without ureteral tailoring is more feasible.

A cutaneous ureterostomy allows decompression of the system and may obviate the need for tailoring of the ureter at subsequent reimplant. However, it does commit the child to a second operation.

If the system is duplicated and no reflux is present in the lower-pole system, a ureteroureterostomy is an attractive approach because it is a single-stage operation with relatively low risk.

Even in infancy, small instrumentation allows ureteroceles that are associated with good function to be endoscopically decompressed with incision. However, this carries the risk of subsequent reflux into that moiety. Incising a ureterocele that is associated with poor function provides little gain. The exception is an infant with urosepsis, but this may be best treated with percutaneous drainage and subsequent reconstruction, depending on the stability of the patient.

Amount of functioning parenchyma

The upper-pole system that serves a duplicated ureterocele typically makes up less than 30% of the unilateral renal function, and preservation of this function is usually not critical. If this poorly functioning moiety is not associated with reflux in other moieties, the best approach is often removal. Conversely, a poorly functioning renal unit that serves a decompressed ureterocele with no reflux has little or no indication for removal.

Intravesical vs extravesical ureterocele

More than 90% of intravesical ureteroceles can be decompressed with endoscopic incision without the need for subsequent surgery for reflux. In endoscopic incision of extravesical ureteroceles, 50% of the cases require secondary surgery.[10]

Detrusor backing

A poorly supported ureterocele that everts during voiding and becomes a bladder diverticulum may be more likely to require secondary reconstruction of the trigone than one that is well supported.

Degree of ureteral dilation

If the ureter that is associated with ectopia or the ureterocele is massively dilated, attempts at reimplantation may be associated with a higher complication rate, such as obstruction and persistent reflux.

Vesicoureteral reflux

Associated VUR may be the single most important predictor of the need for open surgery. Reflux is the major factor that leads to the need for subsequent surgery after upper-pole partial nephrectomy to decompress a ureterocele. If high-grade reflux is associated with a ureterocele, primary endoscopic incision decompresses the ureterocele and facilitates subsequent bladder-level surgery. If no reflux occurs, a simplified approach that consists of only an upper-pole partial nephrectomy may be indicated.

Number of renal moieties involved

Each ureter subtends a separate renal moiety. If only one moiety is involved and is poorly functioning, a single-stage nephrectomy or heminephrectomy is usually curative. The likelihood that this upper-tract approach will be curative diminishes as the number of other moieties involved with either reflux or obstruction increases. In this case, a lower-tract approach in which all problematic ureters can be simultaneously treated is a better option.

Surgical approach

Endoscopic decompression

For intravesical ureteroceles associated with good renal function and associated with either a single or a duplex renal unit, a primary endoscopic approach may be used. A small incision low on the ureterocele is made, creating a flap valve to avoid reflux.

Some series have reported that as many as 90% of patients are adequately treated with endoscopic incision alone.[11] Single-system orthotopic ureteroceles appear to respond most definitively with this approach. A duplex renal system, ectopic ureterocele location, or preoperative reflux suggests trigonal anatomic distortion, increasing the likelihood of a secondary operation after puncture.[12]  

A study by Haddad et al found that the "watering can" endoscopic ureteral puncture approach, in which a laser fiber was used to make 10-20 punctures in the ureterocele, yielded durable successful results at a median follow-up of 2.8 years.[13]

Older age, female sex, and complete ureteral duplication have been associated with a better outcome after dextranomer–hyaluronic acid (DHA) injection.[14] At present, however, DHA is contraindicated by its manufacturer for use in the duplicated collecting system.

Some authors have suggested cystoscopic drainage of an upper-pole obstructed segment in the absence of ureterocele with either stenting or creation of a new orifice into the bladder using a holmium laser to bypass the obstruction as a definitive procedure.[15]

Open reconstruction at bladder level (lower-tract approach)

The ureter is reimplanted into the bladder with an adequate tunnel length to prevent reflux. Any obstructive elements can be excised; if the bladder base is attenuated, it can be reconstructed to provide the ureteral tunnel with good detrusor backing. After tailoring, duplicated ureters can be tunneled in a common sheath or side by side, if indicated, or a ureteroureterostomy can be performed cephalad to the intramural tunnel.

Although this approach may leave a poorly functioning or dysplastic renal moiety in place, this rarely causes a problem that necessitates reoperation in the absence of reflux or obstruction.

Open reconstruction at renal level (upper-tract approach)

When a ureterocele is associated with the upper pole of a duplex kidney, the upper pole often demonstrates poor function. Partial nephrectomy and partial ureterectomy may be performed. This approach is favorable if no reflux occurs because it potentially avoids bladder-level surgery. This procedure is usually performed laparoscopically. This is also the procedure of choice for treating an incontinent girl with poorly functioning renal moiety that drains to an ectopic ureter.

Open reconstruction at renal and bladder level (combined approach)

Some authors still champion the combined approach to open reconstruction, but the procedures require separate incisions and are associated with increased operating time and morbidity. When patients are carefully selected, an upper- or lower-end approach usually suffices and carries minimal risk of necessitating further intervention.

Laparoscopic reconstruction

Laparoscopy is becoming more frequently used to perform ureteroureterostomy and ureteropyelostomy, in addition to more traditional uses such as partial nephrectomy where indicated.[16, 17, 18, 19] Some have argued that in the setting of a poorly functioning upper-pole renal moiety, with other moieties unaffected, a laparoscopic upper-pole heminephrectomy is the procedure of choice.[20]

Robotic assistance has also been successfully applied to the laparoscopic approach.[21, 22, 23, 24]

A single-institution retrospective review by Bansal et al found laparoendoscopic single-site partial nephrectomy to be feasible, safe, and effective for treatment of upper urinary tract duplication anomalies in infants and small children.[25]

A retrospective review (N = 59) that compared partial nephrectomy (OPN; n = 24), laparoscopic partial nephrectomy (LPN; n = 7), robotic partial nephrectomy (RPN; n = 18), and laparoendoscopic single-site partial nephrectomy (LESS-PN; n = 10) for treatment of a nonfunctioning moiety in a duplicated collecting system found that the minimally invasive approaches to partial nephrectomy (ie, LPN, RPN, and LESS-PN) were effective and safe and, as compared with the open approach, were associated with decreased postoperative analgesia requirements, shorter hospital stay, reduced blood loss, and less use of drains.[26]

Short-term complications include UTI, hematuria, and, rarely, significant blood loss. Long-term complications include recurrence of reflux and, more rarely, ureteral obstruction.

Upper- to lower-pole ureteroureterostomy carries a small risk of UTI related to the residual upper-pole ureteral stump. This risk is greater when the diameter of the upper-pole ureter is larger and when reflux into the stump is present.[27] In these situations, an effort to excise the distal stump completely may be warranted.

Heminephrectomy carries some risk of devascularization of the adjacent lower-pole moiety, with loss of some or all of its function. Fortunately, this is uncommon.

Reflux after ureterocele puncture can be seen in the ipsilateral upper or lower moiety or in the contralateral system in nearly half of patients. More than 50% of these cases of reflux may resolve spontaneously; accordingly, conservative management with surveillance is warranted if possible.[28]

Postoperative radiographic imaging with ultrasonography (US) and voiding cystourethrography (VCUG) is warranted to ensure the successful treatment of reflux and the absence of any obstructive element.

Postoperative residual hydronephrosis that may persist for years, even in the absence of obstruction, is common. Imaging is usually repeated serially until the hydronephrosis resolves or stabilizes.

Patients with renal scarring or dysplasia should be observed by their primary care physician with annual blood pressure assessment and urinalysis to rule out proteinuria.