Figure 104-7. Vesicoureteral reflux to the left lower pole ureter.

VUR severity is described using the International Reflux Study scale. Grading is important for several

reasons. Most VUR patients (80%) have grades I or II with an excellent chance of spontaneous

resolution (75% to 90%) over time. The higher grades (III to V) are less likely to improve with time and

more often require surgery. The diagnosis of VUR depends on the demonstration of reflux on an

imaging study. Voiding cystourethrogram (VCUG) is the preferred imaging modality. It offers excellent

anatomical detail of the entire lower urinary tract (bladder and urethra) and reproducible grading. In

males, it provides important details regarding urethra such as possible valves. The presence of other

anomalies such as periureteral diverticulum can affect the clinical decision-making. Alternatively one

can use nuclear cystogram (NUC) that offers less anatomical detail and a different grading system

(grades 1 to 3) but is offset by the advantage of less radioactive exposure and the ability to

continuously monitor reflux throughout filling and emptying. Ultrasound of the kidneys and bladder,

while helpful in assessing renal size and appearance, cannot diagnose reflux. The detection of kidney

scarring is usually confirmed with nuclear renal scintigraphy using DMSA (Fig. 104-8).

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Figure 104-8. DMSA renal scintigraphy demonstrating renal parenchymal defect associated with pyelonephritis. A: Cortical defects

seen in the right kidney during the acute phase of pyelonephritis. B: The same kidney 6 months later showing a persistent cortical

scar involving the upper pole.

The management of children with VUR depends on their presentation and other clinical factors (Fig.

104-9). The vast majority of patients have low-grade VUR and are expected to resolve spontaneously

with time. They can be managed with low-dose antibiotic prophylaxis with intermittent testing every 1

to 2 years. The most recent multi-institution randomized clinical trial suggested that antibiotic

prophylaxis is beneficial in children with dilating, high-grade reflux (grade III or higher). If they cannot

remain infection free and sustain breakthrough infections, surgery may be necessary to prevent

recurrent renal parenchymal infection. For most patients, spontaneous resolution occurs after 4 to 5

years and those who fail to resolve may also need surgery. There are two major surgical options. There

is the less invasive endoscopic approach. Using cystoscope, a small bleb of a bulking material is injected

into the floor of the ureteral orifice. This creates a submucosal mound that turns the usual round oval

opening into an upside-down crescent. Currently, FDA-approved dextranomer/hyaluronic acid

copolymer (Deflux®) is available for this approach. The efficacy of Deflux® injection is good but not

spectacular. About 70% to 75% of VUR can be corrected with this approach. Lower the grade, the more

likely that injection will succeed. The long-term durability also remains unknown. The more time-tested

surgery for correcting VUR is ureteral reimplantation (ureteroneocystostomy), where the ureter is

revised or repositioned to create a more effective ureterovesical flap-valve mechanism by restoring the

submucosal tunnel. The affected ureter is detached and mobilized. A new submucosal tunnel of

sufficient length (more than 4 to 5 times the width of the ureter) is created, and the ureter is placed into

it. It is critical that the muscle underneath the tunnel is firm and secure to allow the collapse of the

reimplanted ureter with bladder filling and emptying. The ureter may require tapering (in megaureter

or obstructed upper pole of duplication anomaly), so it can meet the needed width-to-length ratio of the

tunnel. An extravesical approach is called detrusorraphy, where the muscle flaps are freed from the

underlying bladder mucosa and wrapped behind the ureter at the UVJ to create a more effective flapvalve mechanism. The success rate of open surgery for VUR is very high (96% or more for grades III or

less).

Traditionally, all children who present with a culture-proven UTI were recommended to undergo

evaluation for VUR using ultrasound and VCUG. More recently this paradigm has been called into

question because of the observation that some children seem to tolerate VUR better than others without

long-term clinical problems, especially those with low-grade VUR. A modified evaluation approach

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using the initial ultrasound has been suggested. Because the key concern with VUR is the prevention of

kidney damage and its consequences (hypertension, scarring, and loss of renal function), some argued

that because most VUR are of low grade and most cases of low-grade VUR resolve spontaneously, it

may be reasonable to defer VCUG for only those patients who have recurrent UTIs or whose ultrasound

is abnormal. This led to a major shift in the recommendations from the American Academy of Pediatrics

(AAP) in 2011. Others have argued that determining the presence of renal scarring should be the

dominant factor and advocated an initial nuclear DMSA renal scintigraphy rather than ultrasound.

Recently a double-blind controlled randomized clinical trial looked into the benefits of antibiotic

prophylaxis. The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) study that

completed in 2014 studied 600 children with proven VUR.9 Half received antibiotic prophylaxis and half

received a placebo. Prophylaxis reduced the risk of recurrent UTI by 50%, especially in those with

dilating, high-grade reflux (III to V). The occurrence of new renal scarring however did not differ

significantly between the two groups.

Figure 104-9. International reflux grading system. Majority of reflux are grades I or II, with high likelihood of spontaneous

resolution, whereas higher grades (III to V) with dilating ureters are at a greater risk of UTI, renal injury, and nonresolution, often

requiring surgery.

Women with a history of VUR may be at increased risk later in life for UTI during pregnancy

regardless of whether the VUR was corrected or not. Renal scarring rather than the presence of active

VUR itself appeared to be a key risk factor for pregnancy-related morbidity. In general, for girls with

VUR, the families should be aware that when they become adults of child-bearing age, they need to

know their medical histories, so that appropriate perinatal care and monitoring is instituted.

BLADDER ANOMALIES

Urachal Abnormality

During fetal development, urachus is the cephalad attachment of the cloaca to the allantois. As the

bladder and urethral sphincter develop, it becomes atretic. It remains only as a fibrous cord from the

dome of the bladder to the umbilicus. Occasionally the urachus remains patent either completely or

partially. When completely open (patent urachus), urine can be found exiting the umbilicus. In other

cases, there can be a deep sinus or entrapped cyst. These can be areas that can be infected due to poor

drainage and present with fever, nausea, and umbilical drainage. Detection is usually made by clinical

suspicion, along with abdominal ultrasound or other imaging. Because the epithelial lining of the

urachus is that of the bladder and not of the skin, rarely tumors can occur. Mucinous adenocarcinoma is

thought to arise from the urachal remnant in middle-aged or elderly patients. For this reason, when

detected, even when asymptomatic, some have advocated prophylactic removal.

Exstrophy–Epispadias Complex

During development if the cloacal membrane fails to breakdown at the appropriate time, medial

migration of the mesenchyme to form the anterior abdominal wall is affected. The bladder can end up

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as an exposed urothelial plate (bladder exstrophy) (Figure 104-10).10 The urethra may be incompletely

formed dorsally (epispadias). The whole lower abdomen can be exposed with the hindgut or colon being

unformed with the bladder split into two halves (cloacal exstrophy). Pelvic bone is also abnormally

developed, and there is a diastasis of pubic symphysis.

The least severe manifestation is epispadias. In males, it is a defect with a dorsally placed urethral

meatus and urethra, along with dorsal penile curvature. Visually it looks like a reverse, dorsal form of

hypospadias. When the meatus is very proximal, the bladder neck and continence can be affected. In

females, epispadias typically present with bifid clitoris (Fig. 104-11). It is more commonly associated

with bladder exstrophy, but can occur as an isolated defect. Recognition and protection of the bladder

plate against contact irritation is important. If possible, primary closure of the exposed bladder plate,

pelvic placement and abdominal closure should be done during infancy. Most studies have suggested

that a concomitant pelvic osteotomy is beneficial for successful initial closure as well as the subsequent

bladder function. Repair can be staged with closure of the bladder first, followed by later bladder neck

reconstruction and epispadias repair. Alternatively a complete primary repair could be accomplished

with simultaneous closure of the bladder plate and reconstruction of the epispadias and genitalia.

Bladder exstrophy is associated with other anomalies including inguinal hernia and VUR.

Figure 104-10. Male bladder exstrophy with associated epispadias.

The most severe form of exstrophy disease is the cloacal exstrophy. The hindgut (colon, rectum, and

anus) is absent or rudimentary. The bladder plate is split into two parts on either side of the exposed

cecum and hindgut remnant along with omphalocele. Initial management involves repairing the

omphalocele, creating a colostomy, and dissecting the bladder plates free and reconstruct to form a

reservoir. In cloacal exstrophy, there is also spina bifida with an abnormal sacrum and lower spine.

Figure 104-11. Female epispadias with its classic bifid clitoris.

6 ANOMALIES OF THE URETHRA

Posterior Urethral Valves

305

ior Urethral Valves

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One of the most important obstructive uropathy in males is PUV.11 This condition occurs when a thin

membrane of tissue forms below the verumontanum and above the external sphincter, causing a

blockage of antegrade flow of urine from the bladder. This results in high voiding pressures proximally

leading prostatic urethra dilation, bladder wall hypertrophy (similar to cardiac hypertrophy due to

hypertension or aortic stenosis) and VUR. Most patients today are diagnosed because of antenatal

hydronephrosis. Classic prenatal sonographic findings are bilateral hydroureteronephrosis, large

bladder, and enlarged prostatic urethra (so-called “Keyhole” urethra). The poor bladder emptying

throughout fetal development can result in dysplastic poorly functional kidneys and low urine

production. Oligohydramnios (as result of low urine output) can lead to poor pulmonary development

and concomitant respiratory issues. Initial postnatal treatment is to achieve immediate urethral drainage

(usually with a small diameter feeding tube) and obtain VCUG when stable to establish diagnosis (Fig.

104-12). Most patients undergo endoscopic resection of the valves. If the patient is too small to

accommodate an infant resectoscope (8.5 Fr), a temporary diverting vesicostomy may be appropriate.

Supravesical diversion such as ureterostomy is rarely needed.

There are several long-term urologic concerns for boys with PUVs. PUV remains the leading urologic

cause resulting in renal insufficiency and transplantation. The initial nadir creatinine with complete

bladder drainage is prognostic. Patients with nadir values at or below 0.8 mg/dL seem to be able to

transition into adulthood without needing dialysis or transplantation. The early fibrosis and hypertrophy

of the bladder makes valve boys more prone to develop poorly compliant bladders. These bladders have

higher than normal storage pressures and over time can lead to the development of stones,

incontinence, urinary retention, and worsening renal functions. When recognized early, appropriate

therapy using clean intermittent catheterization (CIC) along with antimuscarinic agents (such as

oxybutynin) to relax the bladder muscle can help manage these so-called “Valve bladders.”

Figure 104-12. Voiding cystourethrogram of a newborn with posterior urethral valve. Bladder wall is thickened from chronic in

utero obstruction. Bilateral severe vesicoureteral reflux is also shown.

7 Hypospadias

Hypospadias occurs when the ventral genital folds do not fuse completely.12 The majority of cases do

not have a known cause. There are a few important associations. When hypospadias is found

concomitantly with an undescended or missing testicle, the probability of a disorder of sex development

(DSD) is high enough to warrant a formal work-up. Recently there has been a growing interest in the

role of endocrine disruptors. These are a class of agents that are not steroids but may act on steroid

receptors. They include agents such as bisphenol A, polychlorinated biphenyls, phytoestrogens, and

other common commercial and industrial compounds. They can fully or partially mimic natural

hormones by binding with androgen receptor, thus altering the effect of endogenous sex hormones.

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There are three anatomic elements in hypospadias: the urethral opening is low, the ventral shaft is

less well developed and classically curves toward the scrotum (called chordee), and the foreskin is

incomplete, being usually absent ventrally and heaped-up dorsally in a hood-like formation (Fig. 104-

13). Most cases (80%) are distal with the meatus being near the tip of the penis or at the neck (corona).

Not all cases require surgery. Milder forms which do not interfere with normal voiding and whose

erections are sufficient for future sexual intercourse may not need correcting, other than cosmetic

concerns.

Surgical repair aims to create a functional penis that allows normal stand-up voiding and straight

erections with good cosmesis.13 The urethral meatus is advanced to normal position on the glans. Any

significant chordee is corrected as well. There are a variety of techniques that can be used depending on

the severity of the hypospadias. These can be done as a single-stage or in multiple stages for the severe

type (Fig. 104-14). The prepuce is a rich source of possible free graft and vascular flaps. When

suspected of having hypospadias, a newborn should not be circumcised until a pediatric urologist has

made an assessment. In some cases, particularly those who had undergone many failed prior attempts at

repair, there may not be sufficient local tissue. Grafts taken from the buccal mucosa of the inner lip or

cheek can be used effectively as a urethral substitute. Complications include urethrocutaneous fistula,

strictures, meatal stenosis, recurrent chordee, and surface skin irregularities. Long-term follow-up is

needed in these patients because complications can occur years after the total repair.

Figure 104-13. Mild hypospadias with urethral meatus located near the neck (corona), along with dorsal hood foreskin.

Figure 104-14. Severe hypospadias with perineal urethral opening along with severe ventral shaft curvature (chordee).

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Disorders of Sex Development (DSD)

When the genitalia do not develop in a manner that is clearly male or female in appearance, the term

disorder of sex development (DSD) is applied.14 It supersedes older terms such as intersex and

hermaphroditism. This is an evolving field and covers a spectrum of disorders, some of which can pose a

significant physiologic and mental health risk. There are daunting concerns over gender assignment and

genital reconstruction. For these reasons, many centers have developed specific DSD teams that aim to

provide a comprehensive, integrated care. Comprised of experts from urology, general surgery,

gynecology, genetics, endocrinology, social work, psychology, and ethics, they develop an organized,

systematic approach to evaluating and treating the patients with DSD while keeping the family

continuously educated as the child grows. Many patients, especially those who were diagnosed late or

who had poor earlier experiences, can have great concerns about secrecy and confidentiality. Much of

what is known of the long-term outcome remains anecdotal and incomplete, lacking robust clinical

outcome data to guide management during infancy.

All patients with suspected DSD require a thorough physical examination, especially of the genitalia

and perineum, along with a detailed pregnancy, family, and social history. Evaluations, including

electrolytes, steroid levels and precursors, gonadotropins, and karyotype, are typically assessed with

further specialized tests ordered as necessary. Imaging includes renal/pelvic ultrasound and genitogram.

Magnetic resonance imaging, cystoscopy, laparoscopy, and gonadal biopsies may also be necessary.

Gender assignment options are reviewed with the family after all information concerning gonads,

chromosome, physiology, fertility potential, and anatomy has been gathered and discussed.

Anomalies of the Penis and Prepuce

As a newborn, most infant boys have a natural physiologic phimosis. It is inappropriate and unnecessary

to retract the foreskin in most boys until they are between ages 5 and 7 years. No special care of the

uncircumcised phallus is needed. Spontaneous separation due to the accumulation of shed skin cells and

secreted oil (forming smegma) and normal erections that occur even in small children naturally lift the

prepuce away from the glans. No forceful retraction should ever be done during early childhood, since it

can be very painful, traumatic, and can result in foreskin tear that will heal as a solid scar.

The indications for neonatal circumcision, arguably the single most common procedure performed

worldwide, remains controversial.15 The clear-cut medical indications are not in dispute – phimosis,

paraphimosis, and balanitis. True phimosis is the inability to retract the foreskin when the child is of an

age when it should have occurred naturally. In milder cases, treatment with topical steroid ointment of

the phimotic ring (such as betamethasone) can sometime loosen up the skin sufficiently that the foreskin

stretches and can be retracted in up to 50%, thus avoiding circumcision. In more severe cases,

circumcision is usually the most straightforward solution, but for families and patients who do not want

to be circumcised a dorsal slit or partial circumcision can be performed. In paraphimosis, the foreskin is

pulled back but cannot be repositioned, causing a vascular constriction in the corona. This is a true

emergency because over time the prolonged retraction will cut off lymphatic and blood flow causing

glandular necrosis. Emergency reduction is needed typically under general anesthesia followed by

circumcision or dorsal slit at a later date. Finally for patients who have recurrent bouts of infection due

to entrapment of bacteria under the foreskin (balanoposthitis), circumcision may be medically

advisable. Circumcision is sometimes advised for boys who have recurrent urinary tract infections,

PUVs, solitary kidney, or VUR to reduce future UTI risks.

Controversy exists for routine neonatal circumcision. This is typically performed as a religious rite,

social or family custom, or concerns about future hygiene. Religious circumcisions are performed as part

of a religious rite for many creeds and sects with the Jewish and Islamic faiths being two of the best

known. In some cultures circumcision is done not because of a religious reason but for a social one – to

be like other older male family members with circumcision. Finally there are some who have

circumcision done because of a concern for future hygiene. After circumcision the covering of the glans

changes from a columnar moist epithelium to a squamous dry and tougher coating. This change and the

exposure of the glans were long theorized to help increase resistance to infection to sexually transmitted

diseases (STD) and UTI. The data from the three large-scale randomized African studies on young men

who underwent circumcision to assess its effect on STD transmission (notably HIV) demonstrated a

statistically significant difference. However, clinically this effect may have limited utility because it

does not prevent or cure any infection – it just proved that the tougher epithelium and a dry

environment may lower infection-carrier risk. Another indication that is sometimes brought up is the

risk of penile cancer. Penile cancer most commonly occurs in the prepuce, thus elective early removal is

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theorized to help prevent later cases. However, the small benefit of reducing a relatively rare condition

while subjecting many children to the risk of circumcision limits this argument. Meatal stenosis occurs

in 5% to 7% of circumcised boys. This occurs when the meatal lips of the urethra rub or chafe against

the diaper or underwear. Irritated by the urine, the raw areas heal to form a thin webbing of skin across

the opening. The classic presentation is upward deflection of stream. It is also a common cause of

dysuria (burning with urination) and terminal hematuria. Treatment is by splitting the web of skin

(meatotomy).

8 ANOMALIES OF THE TESTICLE AND SCROTUM

Undescended or Cryptorchid Testicle

Embryologically, testicle forms just beneath the kidneys.16 During the 12th to 18th weeks of gestation,

the testicles migrate down to a pelvic position just inside the internal inguinal ring. During the third

trimester, the testicle travels through the canal, exits the external inguinal ring and enters the scrotum,

driven by the swelling and contraction of gubernaculum under the influence of androgen. A scrotal

position is advantageous for several reasons. Descended testicles are exposed to a lower temperature

environment, and this is necessary for achieving full sperm development and fertility. Undescended

testicles are also at increased risk for germ cell malignancy. A scrotal position makes self-examination

after puberty easier, thus facilitating an early detection. Finally, undescended testicles that are

positioned near the pubic bone can be more vulnerable to injury.

Physical examination plays a key part in the diagnosis of an undescended testicle. When boys are

anxious or nervous, their inguinal cremasteric muscles tense up and can draw the testicle upward into

the groin. This condition is termed retractile testicles. In most cases, the retractile testicle settles in the

scrotal position by the time the child is ready to start elementary school. In some, retractile testicles can

ascend to the inguinal region as the boys grow older, requiring a surgical intervention. This is referred

as ascending testicle, and may occur up to 5% of boys who are followed for retractile testicles.

About 3% to 4% of normal full-term boys may have an undescended testicle at birth. The incidence is

higher in premature infants. By age 1 year corrected for prematurity, this number drops down to around

1%. This figure remains stable through puberty. For this reason, one must allow (typically during the

first 6 months of life) to see if the testicle will descend spontaneously, but if the testicle has not dropped

by 1 year of life, waiting longer will not improve the situation, and surgical orchidopexy should be

considered. Furthermore, leaving a testicle in an ectopic position beyond age 2 to 3 is thought to

adversely affect future sperm cell (Ad spermatogonia) development. An undescended testicle could be

inside the abdomen, having never engaged the internal inguinal ring. It could be inside the inguinal

canal (canalicular) or through the external ring but not in the scrotum (superficial pouch). It can be

truly ectopic, such as perineal and femoral. Finally, the testicle could be aberrant, dysmorphic, atrophic,

or nonexistent. These are usually testicles, which suffered some form of perinatal vascular compromise

that was not recognized prior to birth. The testicle seems to “vanish” over the first year of life (thus

called vanishing testicle syndrome).

For palpable undescended testicles, the approach is usually through an inguinal incision. The testicle

is mobilized by detaching gubernaculum, cremasteric muscle, and internal spermatic sheath around the

cord structures, and a tunnel is created from the inguinal incision to the scrotum. There is usually an

associated patent processus (up to 80% in infants), and this is separated from the cord and high ligated

at the internal ring. For nonpalpable testicles, the most effective initial approach is laparoscopy. The

key is to find the spermatic vessels. If spermatic vessels pass into the internal ring then the laparoscope

is removed and a groin exploration is done. This may lead to a small undescended testicle, which may

have been difficult to palpate in the inguinal fat. In other situations, there is an atrophic nubbin

(typically within the scrotal sac) due to a probable perinatal torsion and vascular compromise. If the

testicle is seen within the abdominal cavity and well away from the internal ring, the only viable

surgical option may be a Fowler–Stephens orchidopexy (done as either single or two stage), where the

gonadal vessel is divided and the testicle is brought down with a vassal collateral circulation (Figs. 104-

15 and 104-16). In a staged orchidopexy, the dominant gonadal vessel is gently clipped laparoscopically,

allowing the testicle to develop a dependence on the collateral circulation. At a second procedure 6

months or later, the gonadal vessel is divided, and the testicle is carefully brought down (either open or

laparoscopically) with the vasal vessels. Laparoscopy has been shown to be the most effective in

determining the absence of viable testicle (vanishing testicle syndrome). The pathognomonic finding is

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