In Utero Intervention

Since the mid-1980s, surgeons have been cautiously optimistic about the role of antenatal bladder decompression for obstructive uropathy and oligohydramnios. The purpose of this intervention is to restore the amniotic fluid to a more normal volume and thereby prevent pulmonary hypoplasia, which is the pulmonary complication of oligohydramnios. Techniques used include vesicoamniotic shunt placement and cutaneous vesicostomy through hysterotomy.

Moderate enthusiasm for this new technology was generated following a report by Manning and associates of the International Fetal Surgery Registry that suggested that fetal intervention resulted in survival of <44% of cases with oligohydramnios. However, a careful review of all reported cases of fetal intervention for suspected obstructive uropathy yielded only two documented cases in which antenatal bladder drainage could have improved the outcome. More recently, refinements in the technology and better criteria for intervention have allowed the diagnosis and appropriate selection of candidates who may benefit from in utero therapy.

Although fetal sonographic techniques have improved, in some cases, upper urinary tract changes that result from PUV are not apparent before 24 weeks of gestation.

Fetuses with PUV and normal-appearing anatomic features at 20 weeks of gestation are more likely to have normal renal function than those with severe early hydronephrosis. Consequently, antenatal therapy probably would not be beneficial in this group with a better prognosis. A structural ultrasound scan performed at 20 weeks permits systematic evaluation of the urinary tract. The kidneys appear echodense in most cases. Large kidneys with mild parenchymal changes are seen in early obstruction, whereas small kidneys suggest significant parenchymal damage. Discrete focal cysts are a common sonographic manifestation of renal dysplasia.

The ureters are assessed for dilation. Abnormal patency and dilatation of the ureterovesical junction (UVJ) suggest advanced urinary tract changes with poor prognosis. Bladder distention is almost always noted, and the classic “keyhole” sign is observed at times ( Fig. 57.1 ). Bladder wall thickening also should be characterized. Symmetric thickening suggests PUV, whereas asymmetric thickening of the lower half of the bladder relative to the dome region suggests the prune belly syndrome.

Fetal ultrasound scan shows bilateral hydronephrosis (A), right (R) hydroureteronephrosis and a distended bladder (B), and a distended bladder with a “keyhole” sign (C). KIDS, kidneys; L, left; Ureter RT, right ureter.

Because oligohydramnios can be present on the initial examination, amniotic infusion with warm lactated Ringer solution restores the amniotic fluid volume for antenatal sonographic surveillance. The incidence of chorioamnionitis has been reduced by the routine administration of parenteral antibiotic therapy at the time of the infusion followed by 10 days of oral antibiotics. Fetal karyotyping is performed with chorionic villous sampling or cordocentesis to rule out aneuploidy and to confirm the fetal sex. Knowledge of the sex of the fetus is important because shunting of dilated urinary systems in patients who were later found to be female with cloacal malformations provides no benefit in this setting.

Another important selection criterion for antenatal intervention is electrolyte determination on serial vesicocentesis performed at 48- to 72-hour intervals. Normally, fetal urine is hypotonic, whereas urine in renal dysplasia is more likely to be isotonic. Normal fetal urine has a sodium concentration <100 mEq/L, chloride concentration <90 mEq/L, and osmolality <210 mOsm/L. Analysis of fetal urine aspirated from the bladder allows analysis of fetal renal function; urine with normal electrolyte values suggests that fetal renal function will be adequate following bladder decompression. The other important parameter to measure is urinary β ₂ -microglobulin; levels >10 mg/L are highly suggestive of irreversible renal dysplasia. Abnormal fetal urinary values on a single bladder aspiration may be misleading because this value may represent stale urine. Instead, sequential aspiration is more reliable. If the fetal urine parameters improve to normal values, fetal renal function following urinary tract decompression may be acceptable. Using serial vesicocentesis, Freedman et al. reported a 60% survival and a 33% incidence of renal failure in high-risk fetuses identified in the first trimester with severe bilateral hydroureteronephrosis, bladder distention, and oligohydramnios.

Although percutaneous vesicoamniotic shunts have been used for nearly 3 decades, these shunts have significant limitations. Vesicoamniotic shunts become obstructed or displaced in 25% of cases, a situation necessitating additional procedures that can cause increased morbidity in the mother and the fetus, with a 5% procedure-related fetal loss rate. The shunt provides only palliative therapy and does not treat the anomaly or the pulmonary hypoplasia and renal dysplasia that are responsible for up to half of the deaths in patients with PUV.

Despite the advances of the Rodeck shunt, which places the proximal and distal pigtails at 90-degree angles, shunt displacement occurs in 25–30% of cases. The site of shunt placement is important. The shunt must avoid the dome and be positioned in the midline just above the pubic symphysis. Even when no problems with shunt placement and function are noted in the appropriate candidate, unusual and unexpected outcomes can occur. For example, even with appropriate selection criteria and shunt placement, some fetuses have persistent oligohydramnios that leads to fetal demise. These fetuses typically have small kidneys with significant fibrocystic dysplastic changes suggesting progressive degeneration despite successful intervention.

The first reports of percutaneous fetal cystoscopy at 19 weeks and subsequent endoscopic fulguration of the valves were published in 1995. At the time of the initial vesicocentesis, a 0.7-mm fiberoptic endoscope was threaded through the lumen of an 18-gauge thin-walled needle, similar to the technique used to perform transabdominal embryofetoscopy. At 22 weeks’ gestation, a 10-gauge trocar was inserted through the maternal abdomen and into the fetal bladder. A 2.5-mm steerable endoscope with a 1.3-mm operating channel was passed through the trocar. A soft-tip 0.025-inch guidewire was used and the endoscope was advanced along the wire. The valves were electrocauterized with a 2Fr ball-tip monopolar flexible electrode with 25 W of coagulating current. Following the 2-hour procedure, improvement in the urinary tract dilation with restoration of the amniotic fluid was seen on the posttreatment ultrasound scan. Delivery occurred at 31 weeks as a result of preterm labor, and the infant had a postnatal diagnosis of PUV. The remaining patients had prune belly syndrome or were females with urethral atresia or urogenital sinus anomalies. All fetuses underwent karyotyping and serial vesicocentesis for electrolytes, and those with PUV had favorable electrolyte values. Intervention was performed at a weight of 2000 g, with Apgar score of 5 and 7. A 10-mm abdominal wall defect with minor omental herniation was present at the site of the trocar. The infant died of pulmonary hypoplasia on day 4 of life.

More recently, Martinez et al. reported fetal cystoscopic diode laser ablation of PUV in 20 fetuses at a mean gestational age of 18.1 weeks. The median operative time was 24 minutes. Access to the urethra was obtained in 95% and normalization of amniotic fluid and bladder size occurred in 80%. In follow-up, termination of pregnancy occurred in 45%, 73% had “normal” renal function, and 27% had end-stage renal disease (ESRD) and were awaiting transplantation.

Initial Management of Patients With Posterior Urethral Valves

The newborn with PUV may have an abdominal mass (49%), failure to thrive (10%), urosepsis (8%), or urinary ascites (7%). In most cases, antenatal sonography demonstrates bilateral hydroureteronephrosis and a distended bladder ( Fig. 57.2 ). When the bladder is empty, one often feels or palpates a walnut-size, firm mass in the pelvis that corresponds to the trabeculated bladder muscle. In addition, dyspnea associated with pneumothorax or pneumomediastinum may be the initial sign of severe urethral obstruction. A normal urinary stream is an infrequent finding.

Renal ultrasound scan shows severe right hydronephrosis and hydroureter (A), severe left hydronephrosis (B), and voiding cystourethrogram demonstrating typical findings of type I posterior urethral valves (C).

A voiding cystourethrogram (VCUG) should be obtained promptly to establish the correct diagnosis (see Fig. 57.2C ). Sonography usually shows significant bilateral hydronephrosis with a thick bladder. Demonstration of the corticomedullary junction is a favorable prognostic sign for renal function. Conversely, echogenic kidneys, subcortical cysts, and failure to demonstrate the corticomedullary junction on the initial and follow-up ultrasound studies are unfavorable signs.

Antenatal urinomas are thought to serve as a protective mechanism to reduce pressure-related impairment of renal function ( Fig. 57.3 ). Patil and colleagues studied two groups of patients with PUV. Group 1 had ascites with and without urinoma and no vesicoureteral reflux (VUR), and group 2 had urinoma formation alone (unilateral or bilateral) and bilateral VUR. Moderate renal failure was seen in the three boys with ascites alone, and mild renal failure was present in the three boys with urinoma and ascites. The investigators speculated that ascites without urinoma suggests bladder rupture and more severe renal damage. The three boys in group 2 with bilateral urinomas had normal glomerular filtration rates (GFRs), whereas the nine boys with unilateral urinomas showed impaired renal function on the side of the urinoma. These findings were confirmed in a more recent study of 89 boys with PUV, of whom nine had a urinoma. The nadir creatinine (Cr) was significantly lower in boys with urinomas compared with unaffected boys, and none with a urinoma had ESRD or underwent renal transplantation.

Newborn with an abdominal mass. A, Abdominal plain film shows the ground-glass appearance of abdominal ascites. B, Renal ultrasound scan demonstrates an extracapsular urinoma and complete decompression of the collecting system.

Patil and colleagues hypothesized that if renal extravasation is extracapsular, it could have a protective effect on renal function, whereas if the extravasation is subcapsular, the renal parenchyma is compressed, thus possibly leading to the deleterious effects of a urinoma. If the type of urinoma cannot be determined, this may explain the results of other studies that showed no association between renal function and urinoma formation.

The initial treatment for neonates with suspected PUV is directed at decompressing the urinary tract with a small transurethral feeding tube. Attention is given to pulmonary function and fluid and electrolyte management. We recommend passing the catheter at the time of the first ultrasound scan immediately following birth. The catheter can be difficult to pass because of the dilated posterior urethra and the bladder neck hypertrophy. Sonography confirms the placement of the catheter within the bladder because a catheter that is coiled in the posterior urethra will cause the majority of urine to drain around the catheter. Similarly, if too much of the catheter is coiled in the bladder, the tip may extend distally through the external sphincter and provide some drainage of the bladder with continuous leakage around the catheter. Foley catheter use is discouraged because the balloon can obstruct the ureteral orifices when the thick-walled bladder is decompressed, or it can cause severe bladder spasm that can obstruct the intramural ureters. Although anuria can result from the noncompliant, hypertonic bladder wall and can lead to relative obstruction of the UVJ, mechanical occlusion can also be the source of anuria in some cases.

A recent novel approach for temporary bladder decompression was described using a 6Fr 12-cm double J stent advanced over a guidewire. In 30 patients, the mean peak serum Cr diminished from 2.23 mg/dL to 0.56 mg/dL, and the investigators also demonstrated that the stent drained the bladder significantly more efficiently than did either a feeding tube or Foley catheter.

Antibiotic prophylaxis is commonly prescribed. In the absence of suspected sepsis, ampicillin or cephalexin is administered at the time of catheter placement. It is best to avoid nephrotoxic agents that may cause further tubular dysfunction. Finally, neonatal circumcision should be recommended in these boys because it significantly reduces the risk of urinary tract infection (UTI).

Primary Valve Ablation

Infant urethral sounds should be passed to calibrate the urethra. The term newborn male urethra generally accepts an 8Fr endoscope. Dilation of the urethra to pass a larger instrument may lead to urethral trauma and stricture formation. Vigorous dilation may result in iatrogenic hypospadias due to splitting of the glans to the subcoronal level. Vesicostomy is the treatment alternative for the infant whose urethra is too small to accept an endoscope.

Smith and colleagues reported valve ablation using the 6.9Fr cystoscope and the 3Fr Bugbee electrode in premature infants as small as 2500 g. The coagulating current was used to ablate the valves. However, we advocate using a small Bugbee electrode using low cutting current. In older patients, the 11- or 13Fr Storz resectoscope can be used with the cutting current and the right-angle loop. In addition, the neodymium:yttrium-aluminum-garnet (Nd:YAG) or holmium:YAG laser may be used. The Nd:YAG laser was successful in 16 of 20 patients, and four patients underwent repeat valve ablation. In contrast, the holmium:YAG laser was reported to result in improved success in voiding after catheter removal, reduced need for repeat valve ablation, and a lower risk of urethral stricture compared with electrofulguration.

Varying methods are used to ablate PUV. The valves should be incised at the 12-o’clock position and the lateral leaflets should be cut at the 5- and 7-o’clock positions. Passing a cystoscope or resectoscope that is too large may result in urethral stricture. Chertin and colleagues reported a series of 35 cases of valve ablation under fluoroscopic guidance using a 4Fr Fogarty balloon catheter filled with 0.5 mL of saline. A postoperative VCUG revealed no residual valve in 34 of 35 patients (97%). Other methods include creation of a temporary perineal urethrostomy into which the cystoscope or resectoscope is passed or performance of the procedure in an antegrade fashion through a percutaneous cystostomy.

A small feeding tube is left indwelling for 1 to 2 days, and a VCUG may be obtained at the time of catheter removal. If the VCUG is not obtained before discharge from the hospital, it should be obtained 2 to 4 weeks postoperatively to confirm satisfactory valve ablation. In addition, a renal sonogram assesses hydronephrosis and confirms satisfactory bladder emptying.

Another method to assess adequacy of valve ablation is the preoperative and postoperative urethral ratio. This ratio is determined by measuring the diameter of the posterior urethra transversely at a point halfway between the bladder neck and the distal end of the membranous urethra and the diameter of the anterior urethra at the transverse diameter at the point of the maximum distention in the bulbar urethra. Measurements are most accurate on voiding films in which the catheter has been removed ( Fig. 57.4 ). In one study, the median urethral ratio before ablation was 8.6 (range 4–14.7) and that of normal age-matched controls was 2.6 (range 1.3–5.5). The postoperative urethral ratio was 3.1 (range 1.9–4). A second group of patients with a postoperative urethral ratio of 8 (range 5–15.5) after the first ablation underwent a second ablation with a final urethral ratio of 3.1 (range 2.9-6.4). Valve ablation is successful in > 90% of patients. Long-term stricture formation is uncommon.

Posterior urethral measurements to determine the urethral ratio on a preoperative (A) and postoperative (B) voiding cystourethrogram.

(With permission from Bani Hani O, Prelog K, Smith GHH. A method to assess posterior urethral valve ablation. J Urol. 2006;176:303-5.)

Alternatives to Valve Ablation: Cutaneous Vesicostomy and Upper Tract Diversion

An alternative to primary valve ablation is the creation of a temporary cutaneous vesicostomy. A small transverse incision is made midway between the umbilicus and the pubic symphysis, and the dome of the bladder is brought to the skin. If the anterior bladder wall rather than the dome is exteriorized, prolapse may occur. The vesicostomy should calibrate to 24–26Fr to avoid stenosis. In addition, daily dilation of the stoma with a plastic medicine dropper helps minimize contraction of the stoma. The vesicostomy drains into the diaper, and no urinary collection device is necessary.

Cutaneous vesicostomy has been shown to be as effective as valve ablation for initial therapy. This form of management allows the bladder to cycle with voiding at low pressure through the stoma and does not reduce bladder capacity. A cutaneous vesicostomy should not be performed in the presence of active UTI because contraction of the bladder may occur. These babies should be maintained on antibiotic prophylaxis. In some cases, breakthrough febrile UTIs occur and vesicostomy closure is necessary.

In the past, proximal high diversion with cutaneous pyelostomy or cutaneous ureterostomy was advocated for neonates and infants with severe hydronephrosis and a persistently elevated creatinine concentration following catheter drainage. Proximal diversion also provides the opportunity to perform renal biopsy, which may help predict the child’s ultimate renal outcome. The problem with initial high bilateral proximal diversion is that urine is diverted away from the bladder, and this situation may result in a small contracted bladder that does not grow over time.

In boys with PUV, UVJ obstruction usually occurs only during bladder filling and results from elevated intravesical pressure, rarely from obstruction secondary to detrusor hypertrophy. Furthermore, proximal high diversion therapy has not been shown to prevent ESRD because >85% of these patients have renal dysplasia. In addition, by diverting the urine away from the bladder, regular cyclic vesical contraction may not occur and result in a smaller, less compliant bladder compared with vesicostomy. Finally, cutaneous pyelostomies require placement of a diaper across the abdomen and flank, and even then the child’s clothes may become wet. Consequently, this form of diversion generally is reserved for rare cases in which valve ablation or vesicostomy has failed to show improvement in upper urinary tract drainage or when urosepsis is secondary to pyonephrosis.

An alternative form of upper urinary tract diversion is the Sober-en-T ureterostomy, in which the proximal ureter is exteriorized and the distal ureter is kept in continuity with the upper ureter with a proximal ureteroureterostomy. The advantage of this approach is that it permits rapid decompression of the upper urinary tract while permitting urine to pass into the bladder. Fig. 57.5 shows a modification of the original Sober-en-T ureterostomy.

A newborn underwent bilateral cutaneous pyelostomies and transurethral ablation of posterior urethral valves. Before upper tract reconstruction at age 4 years, a catheter could not be passed at the time of the voiding cystourethrogram. The cystogram through a cutaneous ureterostomy shows a complete proximal anterior urethral stricture requiring a perineal approach for reconstruction.

If cutaneous vesicostomy, ureterostomy, or pyelostomy is chosen as initial therapy, valve ablation should not be performed simultaneously because the urethra will remain dry, and urethral stricture formation is common ( Fig. 57.6 ). Another case illustrating the importance of choosing well-planned diversionary procedures and delaying primary valve resection is shown in Fig. 57.7 .

A newborn boy was noted prenatally to have left hydronephrosis and a distended bladder. A, Abdominal plain film shows a large left urinoma. B, Voiding cystourethrogram shows high-grade left vesicoureteral reflux and posterior urethral valves. His creatinine concentration was0.5 mg/dL after 1 week of catheter drainage. During passage of the resectoscope, the glans split, creating a subcoronal hypospadias. Valve ablation proceeded and a left ureterostomy at the midureteral level was performed. Postoperatively, all his urine is noted from the left ureterostomy. Before urinary diversion at age 3 years, a renal scan demonstrates that the left kidney contributes 20% to the total renal function and a cystogram (C) shows reflux into a nondilated left distal ureter, mild trabeculation, and normal capacity for his age (150 mL). Left proximal ureterogram shows no obstruction. Takedown of the left ureterostomy with excision of the left distal ureter and ureteral reimplantation with a psoas hitch are performed. This case demonstrates several points: (1) Ureterostomy is not usually indicated for reflux; (2) ureterostomy should not be performed midureter when reimplantation will be required; (3) once the valve is resected, procedures should not be performed that completely divert urine from the bladder; and (4) care should be exercised when instrumenting the infant male urethra.

A, Sober-en-T ureterostomy decompresses the upper urinary tract and permits urine to pass into the bladder. The proximal ureter is divided below the lower pole of the kidney. The upper end is diverted to the skin. The lower end is anastomosed to the proximal ureter just below the renal pelvis, but not to the pelvis as originally described by Sober. Ureterograms showing the right (B) and left (C) kidneys 1 year after Sober Y-en T ureterostomies. (A, With permission from Liard A, Seguier-Lipszyc E, Mitrofanoff P. Temporary high diversion for posterior urethral valves. J Urol. 2000;164[1]:145-8.)

Prognosis Following Initial Therapy

The prognosis for satisfactory renal function may be predicted by several factors. A serum creatinine concentration >1 mg/dL 1 month following initial treatment or at 1 year of age is associated with late development of chronic renal insufficiency. Other investigators concluded that the most significant prognostic factor for the future development of chronic renal failure is the GFR at 1 year of age, and the development of proteinuria portends a worse prognosis. These investigators found no differences in age at diagnosis, initial management, VUR status, UTI, and hypertension in the development of chronic renal insufficiency, whereas sonographic observations may be useful in identifying patients who will develop renal insufficiency. The presence of the corticomedullary junction on renal sonography has been associated with a favorable outcome. This radiologic finding may not be present on the initial ultrasound study but may become apparent during the first few months of life.

In another study, Duel and colleagues showed that 90% of boys with PUV who were followed for a mean of 8.5 years and who ultimately developed poor renal function had echogenic kidneys, whereas 46% of patients with good renal function also had echogenic kidneys. In addition, 60% of the patients with echogenic kidneys developed poor renal function compared with 13% of the patients with normal renal echogenicity. Increased cortical echogenicity and loss of corticomedullary differentiation were relatively insensitive predictors of eventual renal function in patients with PUV. These investigators found that the serum creatinine concentration following 4 days of catheterization was a more sensitive predictor of outcome in these boys.

Achieving diurnal continence by the age of 5 years also is recognized as a favorable feature. Diurnal incontinence probably is related to detrusor instability and detrusor sphincter discoordination, which can result in elevated upper urinary tract pressures and gradual deterioration in renal function.

A controversial prognostic feature is the presence of a pressure pop-off mechanism, such as massive reflux into a nonfunctioning kidney (termed the VURD syndrome for valves, unilateral VUR, dysplasia), urinary ascites, or a large bladder diverticulum. Although short-term studies suggested that these mechanisms may allow more normal renal development, Cuckow and colleagues reported that at 8–10 years of age, only 30% of boys with the VURD syndrome had a normal serum creatinine concentration. In another retrospective study, Hoag et al. also found that VURD is not a favorable prognostic feature. The finding that pop-off mechanisms may not always be protective was further supported by Patil and colleagues, who observed that ascites may result from bladder rupture, and GFR in those patients approaches the severe renal failure range.

The detrimental or beneficial effects of VUR on renal function in patients with PUV remain controversial. Some investigators suggest that VUR in combination with high intravesical pressure contributes to deterioration of the upper urinary tract; others propose that VUR, especially when associated with the VURD syndrome, protects the upper urinary tract from high intravesical pressures. Hassan and colleagues reported that VUR in their 73 patients did not serve as a significant prognostic factor for renal function. On the other hand, in a long-term study of 197 adults treated over a period of 50 years, Heikkila et al. found that bilateral VUR is often associated with poorly functioning kideys. Persistent VUR with or without renal deterioration in the absence of UTI may indicate bladder dysfunction and the need for lower urinary tract evaluation.

Another adverse prognostic finding is renal parenchymal area <12 cm ² on the first postnatal renal ultrasound, especially when the nadir serum Cr is 0.8 to 1.1 mg/dL. Other adverse predictive factors include oligohydramnios, cortical cysts, and echogenic kidneys. Whether antenatal diagnosis is beneficial is controversial.