Megaureter and Other Congenital Ureteral Anomalies

Interestingly, Leonardo da Vinci and Galen were the first to begin to recognize the importance of the ureterovesical junction (UVJ) and to identify vesicoureteral reflux (VUR). Semblinow's 1883 animal experiments renewed enthusiasm for the study of reflux and began the modern era of research to clarify the anatomy, function, and pathophysiology of UVJ anomalies.

Megaureters

The term megaureter refers to an enlarged ureter. The 4 categories of megaureters are refluxing, obstructing, refluxing/obstructing, and nonrefluxing/nonobstructing. Each category is further divided into primary or secondary, based on either intrinsic or extrinsic causes for their appearance, as follows:

• Primary obstructed megaureter is most commonly caused by an adynamic juxtavesical segment of the ureter that fails to effectively propagate urine flow.

• Secondary obstructed megaureter occurs usually when ureteral dilatation is the result of a functional ureteral obstruction associated with elevated bladder pressures secondary to posterior urethral valves (PUV) or a neurogenic bladder that impedes ureteral emptying.

• Primary refluxing megaureter is associated with severe VUR that alters ureteral efficiency by ureteral distention. The megaureter-megacystis syndrome is an extreme form of the primary refluxing megaureters in which massive reflux prevents effective bladder emptying because urine is passed back and forth between the ureters and bladder.

• Secondary refluxing megaureter occurs secondary to PUV or neurogenic bladder when elevated bladder pressures cause decompensation of the UVJ.

• Primary nonrefluxing/nonobstructed megaureter is diagnosed when no evidence of obstruction or reflux can be demonstrated (diagnosis of exclusion).

• Secondary nonrefluxing/nonobstructed megaureter occurs secondary to diabetes insipidus, in which high urinary flow rates may overwhelm the maximum transport capacity of the ureter by peristalsis, or as the result of ureteral atony accompanying a gram-negative UTI.

• Primary refluxing obstructed megaureter occurs in the presence of an incompetent VUJ that allows reflux through an adynamic distal segment.

Vesicoureteral reflux

A sufficient tunnel length of the submucosal ureter is the most important component of a competent UVJ, as it provides a predominantly passive valve mechanism for ureteral compression and prevents retrograde urine passage. Factors that affect marginal tunnel pressure, causing either primary or secondary reflux, include the loss of UVJ compliance (during UTI), structural weaknesses in the detrusor floor (bladder diverticulum, ureterocele), or excessively high intravesical pressure resulting from neurovesical dysfunction or bladder outlet obstruction (BOO). Reflux resulting from a congenitally deficient UVJ is referred to as primary reflux; reflux resulting from a BOO or neurogenic bladder is referred to as secondary reflux.

A ureteral bud, the early precursor of the ureter, branches off from the caudal portion of the wolffian (mesonephric) duct between the fourth and sixth week of gestation. The cranial portion of the ureteral bud joins with the metanephric blastema and begins to induce nephron formation. The bud subsequently branches into the renal pelvis and the calyces and induces nephron formation. Caudally, the mesonephric duct (along with the ureteral bud) is incorporated into the cloaca as it forms the bladder trigone. Alterations in bud number, position, or time of development result in ureteral anomalies.

Early branching of a single ureteral bud results in incomplete (partial) duplication, with a single ureteral orifice and bifid proximal ureters. An accessory ureteral bud creates complete duplication, with the upper ureter usually protruding into the bladder more medially and inferiorly than the lower ureter. Ectopic termination of a single system or of the ureter of a duplex system is the result of the high (cranial) origin of the ureteral bud from the mesonephric duct. Because of the delayed incorporation of the ureteral bud into the bladder, the resulting position of the ureteral orifice is more caudal and medial or in more severe cases it inserts into one of the Wolffian duct structures as noted above.

The function of the ureter is to effectively transport the urinary bolus from the minor calyces to the urinary bladder at acceptably low pressures. The efficiency of this task depends on adequate coaptation of the ureteral wall to propel the urinary bolus. If the ureter fails to propagate the peristaltic wave, the static urine distends the upper urinary tract and reduces luminal coaptation. Other factors that may affect ureteral transport include urinary volume and bladder pressure.

Frequency

Ureteral duplication

• Ureteral duplication is the most common anomaly of the urinary tract.
• Incidence is as high as 8% in children being evaluated for UTI.
• Incomplete ureteral duplication is observed in approximately 1 in 25 individuals.
• Complete duplication is present in approximately 1 in 125 individuals.
• Complete duplication on one side results in a 40% chance of a complete duplication abnormality on the other side.
• Approximately 10% of siblings may also be affected by complete duplication.

Ectopic ureters

• Incidence is approximately 1 in 2000 newborns. ^[1]
• Approximately 10% are bilateral.
• Ectopic ureters occur more frequently in females than in males (by a ratio of 6:1).
• In females, more than 80% of ectopic ureters drain duplicated systems. In males, most ectopic ureters drain a single system.
• Approximately 80% of all ectopic ureters drain the upper pole of a duplex kidney.
• In males, the ureters always terminate proximal to the external sphincter and may be found at the bladder neck/prostatic urethra (48%), seminal vesicle (40%), ejaculatory duct (8%), vas deferens (3%), or epididymis (0.5%).
• In females, the ureters may terminate at the bladder neck/urethra (35%), vestibule (30%), vagina (25%), or uterus (5%).

Megaureters

• Bilateral involvement is present in about 20% of patients with primary obstructed megaureters.
• Primary obstructed megaureter has a male-to-female ratio of nearly 4:1.
• The left side is more often affected than the right.

Ureterocele

• Incidence is approximately 1 in 4000 children.
• Approximately 80% occur in females.
• Approximately 10% are bilateral.
• Approximately 80% are associated with duplicated collecting systems, with single-system ureteroceles being more common in males and adults.

Vesicoureteral reflux

• Incidence is approximately 1:500 children. ^[2]
• The incidence is approximately 40% in patients undergoing evaluation for UTI.
• VUR is present in 40%-50% of children with chronic kidney disease. ^[2]
• The reported risk of reflux in a sibling is 27%-43%.
• Approximately 50% of the offspring of women with reflux also have VUR.

The outcome of ureteral anomalies chiefly depends on the presence or absence of obstruction and/or infection, and associated kidney injury. In the absence of these, no treatment may be necessary, especially in the case of isolated ureteral duplication anomalies, low-grade VUR, a small orthotopic ureterocele, or a nonobstructed, nonrefluxing primary megaureter. With respect to primary megaureters, as in the case of VUR, spontaneous resolution is common. In the case of the obstructed primary megaureter, spontaneous resolution is less likely to occur; however, one study reported a 70% spontaneous regression.[3]

Cases of high-grade VUR are less likely to spontaneously resolve and more likely to put the kidney at risk of scarring due to pyelonephritis. Prevention of infection is essential to minimize the risk of renal damage; therefore, continuous antibiotic prophylaxis is usually used in children with high-grade VUR while awaiting spontaneous resolution. In the case of obstructive ureteroceles, treatment to relieve obstruction optimizes preservation of renal function, as chronic obstruction can lead to renal deterioration.

No specific clinical signs are associated with ureteral anomalies. In most cases the anomaly is an incidental finding on a routine prenatal ultrasound, and the condition can be addressed before symptoms or infection develop. Some patients present with a urinary tract infection (UTI), abdominal mass, or hematuria. Children with primary megaureters may also present with cyclic abdominal pain/flank pain, or, less commonly, in acute pain crisis.[4]  Patients may present with a cystic mass at the urethral meatus representing a prolapsed ureterocele. In other patients, the diagnosis is incidental after imaging studies for unrelated symptomatology.

Ureteral anomalies may be discovered during the evaluation of a patient with hypertension, proteinuria, or even renal insufficiency (in rare cases of severe bilateral anomalies).

Approximately 50% of females with ectopic ureters present with constant urinary incontinence or vaginal discharge. Consideration of an ectopic ureteral insertion should be given in prepubertal boys with recurrent epididymitis. Postpubertal males with ectopic ureters most commonly present with complaints of chronic prostatitis and painful intercourse and ejaculation. In males, incontinence is never due to an ectopic ureter because the ectopic ureter never inserts distal to the external urethral sphincter.

Urinalysis and urine culture are important in evaluating any young child with an unexplained fever, and the diagnosis of urinary tract infection (UTI) should prompt further radiological evaluation to identify urologic structural anomalies. When structural anomalies are identified in a patient with a febrile illness, it is essential to evaluate for a UTI and, if found, to provide early treatment to minimize the risk of kidney injury.

Renal and bladder ultrasound is a first-line imaging study to evaluate the upper urinary tract (eg, for duplication, dilatation of collecting system, character or thickness of the renal parenchyma) and the lower urinary tract (eg, for bladder wall thickness, ureterocele, diverticulum, posterior urethral dilatation, degree of bladder emptying).

Voiding cystourethrogram (VCUG) permits evaluation of the bladder and urethra (eg, for vesicoureteral reflux [VUR], diverticulum, ureterocele, bladder trabeculation, bladder emptying, urethral anatomy during voiding) as well as assessment of the ureters if VUR is present.

Diuretic nuclear renography is an excellent study to objectively establish differential renal function, cortical scars, and to evaluate the drainage efficiency of the dilated collecting system (eg, washout times).

Intravenous pyelogram (IVP) is a useful study, although it has been largely replaced by ultrasound and nuclear renography. IVP delineates anatomy (eg, dilatation of collecting system, renal or ureteral displacement, bladder wall characteristics) and provides subjective estimation of relative renal function.

Magnetic resonance urography (MRU) provides excellent anatomic and functional evaluation of the renal parenchyma, collecting system and vasculature without exposure to radiation. However, MRU is sensitive to motion artifact and consequently necessitates anesthetic sedation of young children.[5]

See the images below.

Urodynamic studies (eg, flow study, cystometrogram) assess voiding and bladder functional characteristics that are essential in the evaluation of a suspected neurogenic bladder.

Cystoscopy, vaginoscopy, and retrograde pyelogram are endoscopic procedures that allow direct visualization of the genital and lower urinary tracts and may include radiographic visualization of the upper urinary tract (eg, retrograde pyelogram).

Pressure-perfusion studies (eg, Whitaker test) measure differential pressures of the renal pelvis and the bladder. This invasive study, which requires percutaneous renal access, may be useful in evaluating equivocal urinary tract obstruction but is seldom used in the modern era of nuclear renography.

Ureteral ectopia

Single-system ureteral ectopia reveals widespread renal dysplasia in 90% of affected kidneys.

Duplicated-system ureteral ectopia reveals renal dysplasia in approximately 50% of affected renal moieties.

Megaureters

Light microscopy of megaureters demonstrates a predominance of circular smooth muscle; muscle fiber hypoplasia and atrophy, with collagen deposits separating the muscle cells; and mural fibrosis with scant muscle fibers.

Electron microscopy of megaureters demonstrates increased collagen deposition within the adynamic segment.

Increasing experience shows that a considerable number of children with vesicoureteral reflux (VUR), or megaureters without reflux or obstruction, may demonstrate improved renal function on follow-up radiography, without surgical intervention.[6, 7] However, nonoperative treatment mandates close follow-up care in patients with VUR or nonobstructed/nonrefluxing megaureters.

Nonoperative management of VUR and nonobstructed primary megaureter includes antimicrobial suppression, treatment of voiding dysfunction, and regular imaging studies to assess renal growth, renal scarring, and possible resolution of pathology. Bowel and bladder dysfunction are often associated with VUR and increase the risk of pyelonephritis, and so should be evaluated and treated aggressively in children with VUR.

The need for antibiotic prophylaxis in all patients with VUR has been brought into question. Current recommendations include low-dose antibiotic suppression in children younger than 1 year with VUR and a history of febrile urinary tract infection (UTI), based on greater morbidity from recurrent UTI in this population.[8] Use of antibiotic prophylaxis in older children with VUR should be made on an individualized basis; however, the use of prophylaxis would appear to be the most beneficial in those with one or more of the following risk factors:

• Grade 3 or greater reflux
• Female sex
• A significant history of recurrent febrile UTIs
• Bowel or bladder dysfunction

In the absence of obstruction and/or VUR, ureteral duplication anomalies require no specific therapy.

Robotic-assisted ureteral reimplantation has gained popularity and will continue to evolve with time, although open ureteral reimplantation remains the criterion standard for surgical management of VUR. The use of endoscopic injection therapy (EIT) for the treatment of VUR has grown considerably but despite the excellent short-term success rate, increasing reports of complications such as delayed ureteral obstruction and concerns about durability limit the use of EIT.[9]  

The presence of an acute UTI, especially with bullous edema of the bladder mucosa, may be a contraindication to definitive reconstruction. Urinary diversion (eg, ureterostomy, vesicostomy) or drainage may be necessary.

The best approach to the initial treatment of an ecoptic ureterocele without reflux (ie, by endoscopic decompression or by upper pole heminephrectomy) continues to be debated.

Megaureter

In megaureter, indications for surgical intervention are as follows:

• Increasing hydroureteronephrosis
• Decrease in function of the involved kidney
• Development of UTI or recurrent pain

Megaureter secondary to severe VUR or obstruction is usually managed with ureteral reimplantation. Reimplantation techniques are similar to those used for correcting primary VUR. The megaureter can be mobilized via an intravesical, extravesical, or combined approach. Most megaureters will require tapering. The ureteral caliber can be reduced by excising the distal redundant ureter (Hendren technique[10] ) or plication (Kalicinski technique, Starr technique[11] ) to achieve a satisfactory antireflux mechanism. Occasionally, the function of the kidney drained by a megaureter is severely impaired, and nephroureterectomy may be necessary. There have been reports of obstructive megaureters treated successfully by endoscopic dilation.

Laparoscopic-assisted extracorporeal ureteral tapering repair and ureteral extravesical reimplantation has been reported as a safe alternative to open surgery when first-line treatment fails.[12]

Ureteral duplication

Ureteral duplication alone requires no specific intervention. Duplication anomalies with associated pathology, such as VUR or obstruction, require appropriate medical therapy and possible surgical correction.

Ureteral ectopia

Single system

If an ectopic ureter is associated with a single system and the kidney is severely dysplastic or poorly functioning, the recommended treatment is nephrectomy with partial or total ureterectomy. If the involved kidney is functioning satisfactorily, the recommended treatment is ureteral reimplantation. In rare instances of bilateral single-system ectopic ureters, when the bladder capacity is actually adequate for urination, bilateral ureteral reimplantation is performed; if the bladder neck is poorly developed in association with the ureteral ectopia, bladder neck reconstruction (Young-Dees-Leadbetter bladder neck plasty) may be necessary.

Duplex system

Treatment depends on the function of the involved upper pole and whether VUR is present. If function is adequate, a ureteropyelostomy (upper-pole ureter to lower-pole renal pelvis) or ureteroureterostomy (upper-pole ureter to lower-pole ureter) is performed if no VUR is noted in the lower pole ureter. In patients with a functioning upper-pole system and coexisting lower-pole VUR, a common sheath ureteral reimplantation is performed. If the upper-pole moiety is nonfunctional, a partial nephroureterectomy is performed and the upper-pole ureter is removed to the pelvic brim. If patients have coexisting upper-pole VUR, the ureteral stump should be ligated to prevent reflux of urine into the retroperitoneum.

Ureterocele

In ureterocele, indications for surgical intervention are as follows:

• Obstruction
• Urosepsis or compromised renal function may necessitate urgent decompression prior to definitive surgical reconstruction.

Treatment of the ureterocele is based upon relief of obstruction. Endoscopic puncture may be used in cases in which urgent decompression is required (eg, urosepsis, severe compromise in renal function), or it may be used as definitive therapy in the case of a single-system intravesical ureterocele. Endoscopic decompression in cases of ectopic ureterocele constitutes definitive treatment in only 10-40% of cases, as there is frequently associated VUR, which often requires subsequent surgical correction.

Options for open surgical reconstruction include ureteropyelostomy, ureteroureterostomy, excision of ureterocele and ureteral reimplantation, or upper-pole heminephrectomy with partial ureterectomy and ureterocele decompression. In patients with a single-system ureterocele and an associated nonfunctioning kidney, a nephroureterectomy may be performed.

Vesicoureteral reflux

In VUR, absolute indications for surgical intervention are as follows:

• Progressive renal injury
• Documented failure of renal growth
• Breakthrough pyelonephritis
• Intolerance of or noncompliance with antibiotic suppression
• Parental preference

Relative indications for surgical intervention in VUR are as follows:

• Pubertal age
• High-grade (IV or V) VUR
• Failure to resolve

Because the submucosal ureter tends to lengthen with age, the ratio of tunnel length to ureteral diameter also increases, and the propensity for reflux may disappear. Successful nonoperative management of VUR requires preventing renal damage from pyelonephritis and has involved the use of continuous antibiotic prophylaxis and treating bowel or bladder dysfunction.

Dextranomer hyaluronic acid copolymer is a bulking agent for endoscopic treatment of VUR. Endoscopic treatment results in reflux resolution or downgrading in most patients, with long-term success rates of approximately 60-70%.[13] Although not as effective as open ureteral reimplantation, endoscopic correction of VUR offers a minimally invasive, outpatient procedure with a low risk of complications.

In general, ureteral reimplantation has excellent results (>95% success rate). Although the transvesical approach is commonly used, the extravesical approach (detrusorrhaphy) preserves the integrity of the bladder lumen and does not require a ureteral anastomosis. Extravesical reimplantation has been shown to decrease postoperative hematuria, minimize bladder spasms, reduce the need for urethral catheter, and shorten hospital stay. Of note, transient cases of urinary retention have been reported with bilateral extravesical ureteral reimplant. Although open ureteral reimplantation remains the gold standard, minimally invasive techniques (robotic assisted ureteral reimplantation) have demonstrated comparable success rates.[14]

The goals of the preoperative evaluation of the possible ureteral anomaly are as follows:

• Detailed delineation of upper and lower urinary tract anatomy
• Assessment of differential function of each of the renal moieties
• Detection of the presence of anatomical or functional obstruction or VUR
• Evaluation of bladder function

The principles of successful ureteral reconstruction are as follows:

• Adequate ureteral exposure and mobilization with meticulous preservation of blood supply
• Gentle handling of the tissue, and protection of the contralateral ureteral orifice
• With ureteral reimplantation, a submucosal tunnel with a length-to-ureteral diameter ratio of 5:1 to create an adequate valve mechanism to prevent VUR

Howe and Palmer report that Lich-Gregoir extravesical ureteral reimplantation (EVR) using an inguinal approach can be safely and effectively applied to complex cases (eg, megaureter, duplex ureters). In their report on 28 cases, this approach was successful in 94% of tapered EVR and in 92% of common sheath reimplants, with a mean follow-up of 29.6 months. No postoperative obstructions, urinary leaks, or wound infections occurred.[15]

Complications of ureteral reimplantation are uncommon. The most common technical complications are ureteral obstruction, persistent reflux, and diverticula formation. A renal ultrasound should be obtained following surgical correction of VUR to assess for obstruction. Because of the very high success rate of open ureteral reimplantation, a postoperative VCUG is performed only in select cases.

Ureteral reimplantation for megaureter repair is a very safe, reproducible, and successful procedure. The major complications are the development of ureteral obstruction (2-5%) or VUR (approximately 10%). Ureteral obstruction is most likely the result of ureteral ischemia and subsequent fibrosis of an excisionally tapered segment. Initial management of this complication is percutaneous or endoscopic dilatation and stenting of the stricture, but many such instances ultimately require open surgical revision. If postoperative VUR is encountered, a reasonable treatment option is observation and antibiotic prophylaxis because many reflux cases resolve spontaneously.

In addition, VUR is more likely to recur following reimplantation in cases in which bladder pressures are elevated (eg, patients with untreated neuropathic bladders or voiding dysfunction). Treatment of bladder/bowel dysfunction is indicated, preferably prior to surgical intervention of VUR. Careful assessment of voiding symptoms and a low threshold for urodynamic studies are crucial in the evaluation of patients with recurrent VUR.

Follow-up care may include renal ultrasound to assess renal growth and the presence of renal scarring or hydronephrosis. Suppressive antibiotics are discontinued during the postoperative period. Parents are counseled that urinalysis and urine culture are still indicated if their child becomes symptomatic (eg, dysuria, flank pain, hematuria) and that, although their child is at a reduced risk for kidney infection, bladder infections may still occur. Periodic evaluation of voiding symptoms and bladder function may also be included in follow-up care.