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202 Bladder Exstrophy and Epispadias
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Figure 15.7 (a) The Kelly operation.
(I) From the right of the patient,
the penile corpora and urethral
plate are dissected and the bladder is held to the left, the base
of the corpus is separated from
the pubis and moved medially,
the pelvic oor has been released
and the pudendal pedicle is seen
(arrowed). (II) From below the
penis, the urethra has now been
detached, tubularised and brought
between the mobile corpora;
muscle is being wrapped around it.
(b) Kelly operation: postoperative
appearances.
criteria for surgery they also reect the tendency
for authors to assess their results according to
their own denitions of what constitutes urinary
continence. Moreover, authors do not always differentiate between continence with spontaneous
voiding and continence (or dry intervals) in children being managed by clean intermittent catheterisation (CIC) following bladder augmentation.
Meaningful comparisons between surgical results and functional outcomes can only be
obtained if a standardised denition of what constitutes ‘continence’ can be agreed and applied
equally to all patients and treatment modalities.
is does not exist at present. e senior author
has proposed the simple grading system for continence which is illustrated in Table 15.2. Using
this schema, the senior author has assessed the
outcome of 101 patients (70 male and 31 female)
operated between 1999 and 2014. Of these,
56 children were followed-up for at least 5 years
Table 15.2 Grading system for continence
Grade Description
0 Dribbles urine all the time with
no control
I Able to retain urine with a ‘dry
interval’; some control but still
wearing protection
II Sufcient dry intervals by day; in
underwear and not needing
protection; wet at night
III Dry by day and night;
no protection or accidents;
‘normal child’
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and an additional 23 were followed-up over
10 years. In the cohort who had been followedup for 10 years 81% of males achieved dryness by
day (grade II) and 44% were dry at night (grade
III). Overall, 13% of males required bladder augmentation surgery. Sixty-seven percent of females
were dry by day (grade II) and 33% were dry by
day and night (grade III). Bladder augmentation
was required in 33% of females. Our experience
indicates that the Kelly procedure provides a
relatively predictable degree of outow resistance and that continence is then dependent on
the bladder’s ability to increase its capacity in
response to this enhanced outow resistance.
Persisting incontinence may be due either to
inadequate outow resistance and/or inadequate
bladder capacity. Some degree of spontaneous
improvement can usually be expected with further growth – particularly around puberty. In
children with severe incontinence, however, it
is usually necessary to perform a repeat bladder
neck reconstruction in combination with ileocystoplasty and the formation of a Mitrofano catheterisable channel. Ideally this should be timed to
enable the child to become continent by around
the age of 6 years. Incontinence which is due to
poor outlet resistance can sometimes be reduced
by cystoscopic injection of a bulking agent such
as Deux (dextranomer/hyaluronic acid copolymer) into the region of the bladder outlet. If the
incontinence persists despite this and similar
measures the only remaining option may be surgical closure of the bladder neck.
Late Outcomes
Woodhouse has documented the late outcomes
of reconstructive surgery in exstrophy patients
and although some of the ndings relate to
outdated forms of surgical management, such
as ureterosigmoidostomy, they nevertheless
highlight the importance of long-term followup. Renal damage (due to a combination of
lower tract obstruction, vesicoureteric reux
and urinary infection) was identied in 25% of
patients. Follow-up data indicate that patients
who achieve continence following a tight bladder neck procedure in childhood may be at
increased risk of decompensation and detrusor
failure in later adolescence. Intermittent catheterisation is indicated in such cases – either
via the urethra or via a Mitrofano catheterisable conduit (which is usually accompanied by
augmentation cystoplasty). Stone formation has
been reported to occur in up to 25% of patients.
e risk of malignancy in the reconstructed
exstrophy bladder has been estimated to be in
the region of 4% aer 30 years of follow-up.
Males have normal sexual libido and 90% can
achieve erections, although some require corrective surgery for severe persistent dorsal chordee.
e majority can experience orgasm but may have
slow or retrograde ejaculation due to abnormalities of the proximal urethra. Fertility is reduced,
probably as a result of disruption of the ejaculatory ducts during bladder neck surgery or the
consequences of episodes of epididymo-orchitis,
which occur in up to one-third of men. e fertility rate in men with exstrophy is around 20%.
However, recent studies of quality of life scores in
relation to sexual function are comparable to the
normal population.
For females, surgery to the introitus may be
required to facilitate intercourse but the prospects
for fertility are normal. Pregnancy is oen complicated by vaginal prolapse although this may
prove to be less problematic following contemporary surgical procedures. Delivery by caesarean
section is recommended and it is prudent to have
a urologist in attendance for patients who have
previously undergone bladder augmentation.
Unfortunately, there are some exstrophy
patients who have a history of multiple failed operations which is sometimes accompanied by loss of
penile corpora and compromised renal function.
For these patients, major and complex revisional
surgery is required. (See also Chapter 24.)
CLOACAL EXSTROPHY
Initial Presentation and Management
Cloacal exstrophy is more likely to be diagnosed
prenatally than bladder exstrophy because of
the associated anomalies, which are listed in
Tab le 15.3. Aected infants are frequently born
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Table 15.3 Associated anomalies in cloacal
exstrophy
Cases
Anomaly
Renal anomalies
Ectopic kidney, agenesis,
hydronephrosis
Sacral agenesis 60
Spinal dysraphism
Myelomeningocoele, lipoma,
tethered cord
Orthopaedic deformity
Club foot, hip and pelvic
deformity
Small bowel defects
Malrotation, duodenal atresia,
short gut
Cyanotic heart disease <10
affected (%)
7
50
40
65
prematurely and cloacal exstrophy may be only
one of many problems. Primary closure is usually delayed, oen for several months, while other
medical conditions aecting the gastrointestinal
tract and cardiorespiratory systems are evaluated and managed. Pending surgery, the exposed
bladder/bowel plate is protected with plastic lm
and barrier creams are applied to the surrounding skin. In very low birth weight babies, enteral
feeding is established with a target weight of
2.5–3 kg being set before closure is undertaken.
If an exomphalos is present, this can usually be
managed expectantly since it tends to contract
spontaneously without the need for surgical
intervention.
Preoperative evaluation includes ultrasound
scans of the urinary tract and spinal cord. Iliac
pelvic osteotomie s are invariably requi red because
of the delay in closure and the wider pelvic diastasis in these patients. Although osteotomies help
to facilitate tension-free closure of the abdominal
wall this may not be achievable if the abdominal
contents cannot be accommodated within the
abdominal cavity. In this situation, a plastic silo
or mesh is attached over the upper abdomen to
reduce tension and is then gradually reduced and
removed over the following days. At operation,
the bladder/bowel plate is dissected free from the
skin and rectus muscles superolaterally and the
abdominal cavity is entered. e proximal and
distal loops joining the midline bowel plate are
identied and separated from the two hemibladders. A tubularised distal hindgut tube is created,
which is usually brought out in the le iliac fossa
as an end colostomy (in preference to an incontinent anal canal). e hemibladders are joined
and closed prior to reconstruction of the bladder
outlet and proximal urethra (Figure 15.8).
Gender of Rearing
Historically, males with cloacal exstrophy were
oen assigned to female gender because of the
severity of their genital anomaly and diculty in
reconstructing a functioning penis. is approach
is no longer generally practised in the UK because
of greater understanding of the role of hormonal
Figure 15.8 Male cloacal
exstrophy, closed at three
months. Osteotomies enable
the bladder plates and
hemiphalli to be brought
together in the midline. In
addition, there has been an end
colostomy and umbilicoplasty.
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factors responsible for male gender imprinting in
intrauterine life.
Initial Outcomes
Although prematurity, severe cardiac anomalies
and complications relating to short bowel and
parenteral nutrition pose an increased risk of
early mortality, the majority of aected newborns
now survive into childhood. Careful surveillance
of the upper urinary tracts is important in safeguarding long-term renal function. Magnetic
resonance imaging (MRI) is used to assess the
need for neurosurgical intervention for spinal
dysraphism and orthopaedic input may also be
required for the correction of any limb abnormalities. Colostomy complications occur in around
50% of patients and it is occasionally necessary to
remove the reconstructed hindgut and replace it
with an ileostomy.
Continence and Long-Term
Outcomes
e combination of exstrophy and neuropathic
dysfunction inevitably means that all patients will
require enterocystoplasty if they are to achieve
continence and storage of urine at safe pressures.
Augmentation of the bladder may be dicult if
only a short length of small bowel is available and
there is no usable appendix. Nevertheless, most
children can be successfully managed with ileocystoplasty and Mitrofano or Monti procedure.
If there is insucient small intestine, the alternatives for augmentation include a patch of stomach
or a hindgut segment. e more complex forms
of reconstruction carry the highest risk of failure
and any coexisting renal insuciency will also
contribute to greater overall morbidity.
Some individuals with severe forms of cloacal exstrophy will suer lifelong urinary incontinence regardless of advances in reconstructive
surgery. Although male infants are now almost
invariably assigned male gender at birth they may
be destined to encounter serious diculties relating to sexual function in adulthood. Moreover,
the combination of reduced penile size and surgical damage to vasa deferentia and ejaculatory
mechanisms result in high rates of infertility.
PRIMARY EPISPADIAS
Presentation
Primary epispadias is rarely identied prenatally but is usually detected at birth. In milder
(glanular) forms of the anomaly, however, the prepuce is intact and the condition may not become
apparent until the prepuce becomes retractile.
In girls, the diagnosis of primary epispadias is
oen considerably delayed because most junior
paediatricians are unaware of this rare anomaly
and fail to identify it on routine neonatal examination. e classic presentation is with a history
of dribbling or stress incontinence and failed
toilet training. e diagnosis is readily apparent
when examination is undertaken by someone
with knowledge of the appearances of the genitalia in this condition (Figure 15.5).
Management
Males
e widely used Cantwell–Ransley epispadias
repair can be performed in the rst year of life.
In this operation the exposed urethral plate is le
attached distally to the glans but the entire length
of the exposed urethral plate is otherwise mobilised from the penile corporeal bodies before being
tubularised and relocated to lie in a ventral position inferior to the corpora. Approximation of
the two corpora in the midline then has the eect
of eliminating the dorsal curvature (chordee) of
the penis. A Heineke–Mikulicz type glans plasty
procedure is performed at the distal end of the
tubularised urethral plate to create a more ventrally located meatus.
For patients with good penile length this operation is usually successful in creating a terminal urethral orice and achieving a satisfactory cosmetic
outcome. Where the penis is smaller, the phallus
may appear shorter with a rather buried appearance. In these patients, penile mobilisation provided by the Kelly operation enables its length to be
enhanced, particularly if there is a pubic diastasis.
Epispadias is commonly associated with incontinence due to sphincter weakness and deciency
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of the bladder neck. Although it is not possible to
reliably assess continence in infants who are still
in nappies, some indication can be provided by
the penile anatomy (severity of epispadias) and
the cystoscopic ndings. e Cantwell–Ransley
repair is indicated in boys with more distal epispadias if the penis is of good size, the verumontanum is distal to the bladder neck and they appear
to void without dribbling. For those with more
severe primary epispadias the Kelly procedure is
more appropriate. e technical aspects are the
same as those employed in bladder exstrophy.
Outcome
e long-term outcome for sexual function is
usually good with normal fertility unless there
have been urethral complications or epididymoorchitis. However, ejaculation may be slow or
even retrograde. Patients who have only undergone penile reconstruction (the majority) will
require additional bladder neck/sphincter surgery if their continence is impaired. Injection of a
bulking agent into the bladder neck may improve
continence in the short term but the benet is not
sustained. e surgical options then comprise a
bladder neck repair or implantation of an articial urinary sphincter. In some patients it may
be necessary to progress to bladder augmentation and a Mitrofano conduit. Although the
Kelly operation oers enhanced penile length, it
remains unclear whether the sphincteric reconstruction included in the procedure will lead to
improved continence in due course.
Girls
Since the majority of girls with epispadias are
incontinent, reconstructive surgery must be
directed at treating the incontinence as well as
correcting the genital abnormality. Good results
have been reported following distal urethral
reconstruction, but more proximal bladder neck
surgery may also be required. e Kelly procedure oers the prospect of a favourable prognosis for continence combined with a satisfactory
external cosmetic outcome. ere should be a few
implications for sexual function or fertility.
Other Bladder Disorders
Bladder diverticulum
A diverticulum is an outpouching or ‘herniation’
of the bladder lining, which protrudes through
the bladder wall into the peri vesical space.
Diverticula can be classied as primary or seconda r y. Primary bladder diverticula are congenital abnormalities of the bladder, which occur
mainly in boys. Connective tissue disorders
such as Ehlers Danlos syndrome and Menke’s
syndrome are also associated with bladder
diverticula – as is Williams syndrome. Primary
paraureteric diverticula are located adjacent to
a ureteric orice and may be accompanied by
VUR. Secondary bladder diverticula of varying size develop as a consequence of exposure of
the bladder wall to grossly elevated intravesical
pressure. Small diverticula are termed ‘saccules’.
Conditions giving rise to severe outow obstruction, such as posterior urethral valves, syringocele
and urethral strictures are oen accompanied by
secondary diverticula – as are functional bladder
disorders causing grossly elevated intravesical
pressure, such as neuropathic bladder and severe
dysfunctional voiding with detrusor-sphincter
dyssynergia (Hinman syndrome).
Diagnosis
Small, secondary diverticula are generally identied as asymptomatic ndings on bladder ultrasound or MCUG during routine evaluation of
urological conditions, such as posterior urethral
valves. Primary diverticula are usually diagnosed
when they are identied on an ultrasound scan
performed during initial investigation of children
(mainly boys) presenting with voiding symptoms
or urinary tract infection.
Management
Secondary diverticula rarely require treatment and tend to resolve or reduce in size aer
appropriate treatment of outow obstruction or
bladder dysfunction. By contrast, surgical intervention is oen indicated for large congenital
primary diverticula, particularly when they are
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located in the region of the bladder neck and give
rise to obstructed voiding. Diverticulectomy is
also indicated for a large diverticulum with a
narrow communication to the bladder lumen
in which stasis of urine poses a risk of infection,
stone formation and possible late malignancy.
Surgery (which can be performed by either
an open or laparoscopic approach) consists of
removing the diverticulum and repairing the
defect in the bladder wall.
Urachal Anomalies
e urachus (communication between the bladder and amniotic cavity) normally closes around
the 12th week of gestation to leave a brous cord
(median umbilical ligament).
A number of abnormalities can result from
incomplete or aberrant closure.
In around 10% of cases, the urachus remains
open along its entire length to constitute a patent
urachus. is may occur in conjunction with
congenital abnormalities of the bladder, such as
prune-belly syndrome or as an isolated anomaly. Typically, a patent urachus presents in the
neonatal period with oozing of clear uid from
the umbilicus or periumbilical infection and/or
granulation tissue.
Urachal sinus accounts for approximately 50%
of cases. In this variant, the portion of urachus that
was connected to the bladder closes normally but
the rest of the urachus remains patent and in communication with the umbilicus. Presenting features may include; purulent umbilical discharge,
fever, lower abdominal pain and tenderness.
Urachal cysts account for approximately 30%
of cases. Both ends of the urachus close normally
but a central section remains patent to leave
an isolated, non-communicating cystic cavity.
Urachal cysts present at a later stage in childhood
than other urachal abnormalities – typically as
a lower abdominal mass, which may be complicated by infection. Very rarely a blind-ending
length of patent urachus remains in communication with the bladder to create a non-obstructive
diverticulum, which is discovered as an incidental nding on an ultrasound scan or micturating
cystourethrogram (MCUG).
Investigation and management
Depending on the presentation, this may involve
ultrasound, MCUG and magnetic resonance
imaging (MRI). Additional contrast studies
(sinography) may also be required to delineate
the anatomy. Management is aimed initially at
treating any infection with antibiotics and surgical drainage if necessary. Once infection has
been eradicated and the anatomy has been established, treatment usually consists of surgical excision. Asymptomatic cysts should also be excised
because of the documented long-term risk of
adenocarcinoma.
KEY POINTS
●
e exstrophy–epispadias complex
encompasses a group of rare anomalies,
which occur more commonly in males.
●
Cloacal exstrophy is usually detected
antenatally, as are more than half of all
cases of bladder exstrophy. Epispadias,
however, is almost invariably diagnosed at birth.
●
Most infants with uncomplicated or
classic bladder exstrophy are otherwise
healthy, and surgical correction can be
undertaken safely within the rst few
days or weeks of life. e cosmetic and
functional results obtained with the
one-stage Kelly operation may prove
to be superior to those achieved with
conventional staged repair.
●
Late morbidity is common in exstrophy
patients and may include incontinence,
sexual dysfunction and renal impairment. It is hoped that newer techniques
will oer better long-term results.
●
Cloacal exstrophy is oen associated with prematurity or other
medical problems, which take priority over early surgical correction.
Reconstruction presents a formidable
challenge. Although it is usually possible to create a urinary reservoir, most
patients are le with a permanent
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colostomy. It may be necessary to consider gender reassignment in severely
aected males.
●
Primary epispadias is commonly
associated with incontinence due to
deciency of the bladder neck and
sphincter complex.
FURTHER READING
Gearhart J P, Jeffs RD. Exstrophy–epispadias
complex and bladder anomalies. In:
Walsh PC, Retik AB, Vaughan ED, Wein
AJ (eds), Campbell’s Textbook of Urology,
7th Edition. Philadelphia: WB Saunders,
1998: 1939–1990.
Kelly JH, Eraklis AJ. A procedure for lengthen-
ing the phallus in boys with exstrophy of the
bladder. J Pediatr Surg. 1971;6:645–649.
Siffel C, Correa A, Amar E, et al. Bladder
exstrophy: an epidemiologic study from the
international clearinghouse for birth defects
surveillance and research and an overview
of the literature. Am J Med Genet C Semin
Med Genet. 2011;0(4):321–332.
Woodhouse CRJ. Exstrophy and epispadias.
In: Long-Term Paediatric Urology. London:
Blackwell, 1991:127–150.
Woodhouse CRJ. Genitoplasty in exstrophy
and epispadias. In: Stringer MD, Oldham
KT, Mouriquand PDE (eds), Paediatric
Surgery and Urology: Long-Term Outcomes.
Cambridge: Cambridge University Press,
2006:583–594.
16
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Hypospadias
NADIA V HALSTEAD, PIERRE D E MOURIQUAND and DUNCAN T WILCOX
Topics covered
Etiology and incidence
Disorders of sex development and associated
anomalies
Surgical principles
Overview of surgical techniques
Chordee correction
INTRODUCTION
Hypospadias is an association of three anatomical anomalies:
●
an abnormal ventral opening of the urethral
meatus;
●
ventral curvature (chordee) of the penis;
●
a dorsal hooded foreskin with ventral
deciency.
However, not all three of these features are present in every case.
Hypospadias is better dened as a hypoplasia of
the tissues forming the ventral aspect of the penis
beyond the division of the corpus spongiosum. It is
characterized by a ventral triangular defect whose
apex is the division of the corpus spongiosum; the
sides are represented by the two pillars of atretic
spongiosum and the base is the glans.
Tubularization
Two-staged repair
Urethral repositioning
Pedicle- and meatal-based aps
Outcome and complications
ETIOLOGY AND INCIDENCE
e incidence of hypospadias is generally quoted
at 1 in 300 live male births (0.33%). However,
data from dierent countries show considerable
variation, with reported incidences ranging from
0.006–0.7% in Asia to 0.2% in Europe to 0.34%
in North America. Hypospadias appears to be
increasing in frequency. e apparent increase
in the incidence of hypospadias, coupled with
the increasing incidence of testicular cancer and
declining semen quality, have been cited as examples of the possible impact of estrogenic environmental pollutants (“endocrine disruptors”) on
normal virilization of the male fetus. Phthalates,
phytoestrogens (found in soy), and mycoestrogens
have been identied as some of the environmental
pollutants associated with hypospadias. In addition, endocrinopathy, low birth weight, maternal
hypertension, maternal vegetarianism, conception
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via intracervical semination and in vitro fertilization, and advanced maternal age (possibly mediated by placental insuciency) have been identied
by some studies as possible etiological factors.
GENETICS
By contrast to the uncertainty surrounding the
extent of the role played by environmental factors, the importance of genetic factors has been
reliably documented in numerous studies. e
incidence of hypospadias in rst degree relatives is of the order of 7–10%, rising to 20% in
the siblings of boys with severe hypospadias.
ere is also an association with certain genetic
syndromes including WAGR, Denys-Drash, and
Opitz. However, genetic factors apply mainly to
the more severe forms of proximal hypospadias
whereas distal forms are more likely to occur
as sporadic (non-inherited) anomalies. Defects
in genes expressed during development of the
genital tubercle and urethral plate have been
implicated in the etiology of hypospadias. ese
include SHH, GL1, GL2, GL3, FGF8, FGFR2,
WT1, BMP 7, WNT5A, and DGKK. Mutations
in homeobox genes (HOXA13, HOXA4, IRX5,
IRX6), genes involved in androgen production
and signaling (HSD3B1, HSD17B3, SRD5A2,
AR), and estrogen production and signaling
(ESR1, ESR2, ATF3, VAMP7) have also been
identied in some patients and have also been
studied experimentally in “knock out” mouse
models.
DISORDERS OF SEX
DEVELOPMENT (DSD) AND
ASSOCIATED ANOMALIES
Severe forms of hypospadias can present with
similar appearances to disorders of sex development (DSDs), especially when severe hypospadias is associated with undescended testes and
a prostatic utricle. In some series, up to 50% of
patients with both hypospadias and cryptorchidism have been found to have an underlying
genetic, gonadal, or phenotypic sexual abnormality. It is essential that all patients with hypospadias who have undescended testes are fully
investigated so that DSD can be excluded. Apart
from an increased overall incidence of undescended testis, other anomalies in patients with
isolated hypospadias are rare. Abnormalities of
the urinary tract are uncommon, occurring in
approximately 2% of patients. For this reason,
routine ultrasound screening is unnecessary. e
overall incidence of undescended testis is in the
range 5–10%, rising to 50% in those with severe
perineal or penoscrotal forms of hypospadias.
ese severe forms are also associated with a persistent prostatic utricle in 20% of cases. When
this is present it can create diculties with urethral catheterization of the bladder. But since it
is rarely necessary to remove a prostatic utricle,
cystography, or cystoscopy to look for a possible
utricle are not routinely required and need only
be performed if the child is symptomatic.
CLASSIFICATION
Although many classications have been
described based on the position of the ectopic
urethral meatus (Figure 16 .1), the level of division
of the corpus spongiosum may provide a more
accurate means of distinguishing anterior hypospadias with little or no chordee from posterior
hypospadias with chordee and hypoplasia of the
tissues forming the ventral aspect of the penis
(Figure 16.2). In approximately 70% of cases, the
urethral meatus is located on, or adjacent to, the
glans or on the distal penile sha. In the remaining 30% of cases, the meatus is more proximal
(midsha to perineal) and the anatomy is more
complex.
e authors’ classication, therefore, recog-
nizes three main types of hypospadias.
1. Hypospadias with a distal division of the
corpus spongiosum with little or no chordee.
2. Hypospadias with a proximal division of the
corpus spongiosum with a marked degree of
hypoplasia of the ventral tissue and a signicant degree of chordee.
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Figure 16.1 Standard classication of hypospadias.
3. Hypospadias which persists despite multiple
previous operations. (Patients with this condition were previously termed “hypospadias
cripples”).
SPECIFIC SURGICAL PRINCIPLES
Although more than 300 dierent techniques have
been described for the repair of hypospadias, the last
decade has seen the emergence of a growing consensus amongst specialist hypospadias surgeons. For
most patients this comprises either tubularization
of the urethral plate or a two-stage repair – usually
involving a free ap. is chapter will concentrate
on these two techniques, but other methods that are
still in current use will also be described.
Regardless of the repair, there are three specic components to the surgical correction of
hypospadias:
●
Correction of the penile chordee
●
Reconstruction of the urethra (urethroplasty)
Figure 16.2 Deceptively severe case illustrating
the potential pitfalls of classication based on
the position of the urethral meatus. The urethra
terminates with an opening on the glans but the
entire urethra is “paper thin” and this case is,
in effect, a proximal form of hypospadias with
chordee.
●
Skin coverage of the penis aimed at achieving
a normal cosmetic appearance
In general, surgical correction is recommended
between 6 months and 18 months of age with the
aim of achieving an optimal cosmetic and functional outcome.
Correction of Penile Chordee
Penile chordee can result from several factors
including ; abnormal tethering of the penile sha
skin on to the underlying structures, tethering
of the urethral plate to the corpora cavernosa
or atretic corpora spongiosum tissue extending
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