EPISPADIAS EXSTROPHY COMPLEX
The exstrophy-epispadias complex encompasses a spectrum of disorders thought to represent increasingly severe defects in infraumbilical midline development. There is invariable involvement of the urinary tract and genitalia, and there may also be involvement of the abdominal wall, anus, pelvis, and spine. The timing and nature of the underlying embryologic defect are thought to determine which structures are involved, and thus which condition in the complex will result. In order of increasing severity and multisystem involvement, the conditions in the complex are known as epispadias, bladder exstrophy, and cloacal exstrophy.
Epispadias, the least severe condition, features an open defect in the dorsal wall of the urethra. As a result, the urethra becomes a ﬂat strip of exposed mucosa. In males, this strip begins at the external meatus and continues proximally either to the base of the glans (balanic epispadias), base of the penis (penile epispadias), or bladder neck (penopubic epispadias). In penopubic epispadias, the defect usually leads to absence of the normal sphincter mechanisms, resulting in urinary incontinence. In females, the dorsal urethral defect may likewise be short, resulting in a patulous urethral oriﬁce, or more extensive, causing an open defect that reaches the neck of the bladder.
Bladder exstrophy is a more severe condition in which there is failed closure of the anterior abdominal wall in the midline. In addition, there are multiple abnormalities of the bony pelvis, including a wide pubic diastasis. The umbilicus is low set and marks the cranial extent of the abdominal wall defect, whereas the anus is anteriorly displaced and marks the caudal end of the defect. The anterior wall of the bladder is absent, and the everted posterior wall of the bladder is exposed through the abdominal wall defect. The ureteric oriﬁces are visible and laterally displaced, with shortened intramural segments. Epispadias is always present. Males have a foreshortened penis, which reﬂects both a reduction in anterior corpora cavernosal tissue, as well as retraction of cavernosal tissue secondary to the pubic diastasis. Females have a biﬁd clitoris and foreshortened vagina. Umbilical and indirect inguinal hernias are often present.
Cloacal exstrophy is the most severe condition in which bladder exstrophy is accompanied by bladder division, exstrophy of the terminal ileum between the two halves of the bladder, a blind-ended hindgut, imperforate anus, omphalocele, complete phallic division (in males), complete vaginal and uterine duplication (in females), and spinal defects.
Bladder exstrophy is the most common of these three anomalies. The incidence is reported to be between 2.1 and 4 per 100,000 births, although it has been declining, likely due to prenatal diagnosis and termination of affected fetuses. There is at least a 2 : 1 male-to-female ratio, with some series reporting an even higher male predilection. Isolated epispadias occurs in approximately 1 in 117,000 males and 1 in 484,000 females. Finally, cloacal exstrophy occurs in 1 in 200,000 to 1 in 400,000 births.
The embryologic defect underlying the epispadiasexstrophy complex is poorly understood. The most prominent theory argues that the main defect lies in the cloacal membrane, the bilaminar structure consisting of ectoderm and endoderm that is situated anterior to the cloaca (see Plate 2-3). In normal development, the cloacal membrane occupies a large territory on the ventral surface of the embryo just inferior to the body stalk. As development proceeds, however, mesoderm invades the cranial aspect of the cloacal membrane, interposing itself between the ectoderm and endoderm. This mesoderm, which now occupies the infraumbilical space, fuses in the midline and gives rise to the infraumbilical abdominal wall, pubic rami, and anterior surface of the detrusor muscle. In addition, specialized regions of the mesoderm form the paired genital folds, which fuse in the midline to form the genital tubercle (see top left illustration in Plate 2-4). In the meantime, the cloaca undergoes septation into an anterior urogenital sinus and posterior rectum, the oriﬁces of which become exposed following apoptosis of the cloacal membrane.
If the cloacal membrane does not permit mesodermal invasion, midline fusion of the mesodermal structures is not possible, resulting in midline defects of the abdominal wall and pelvis. In cloacal exstrophy, this defect is hypothesized to occur in conjunction with abnormal cloacal septation. As a result, both the bladder and hindgut become exposed through the abdominal wall defect following apoptosis of the cloacal membrane. In addition, the cloacal membrane prevents fusion of the genital folds, causing the genitalia to appear biﬁd. Meanwhile, in both bladder exstrophy and epispadias, impaired mesodermal invasion occurs in conjunction with normal septation of the cloacal membrane. As a result, the abdominal wall defect exposes either the urethra alone or both the urethra and bladder, depending on its size. In either case, it appears that the genital folds fuse to a large extent at the level of the urorectal septum, caudal to the urogenital sinus. In males, this arrangement would explain the presence of the urethra on the anterior surface of the undivided penis.
Presentation And Diagnosis
The diagnosis of bladder exstrophy can be established using prenatal ultrasound performed after 15 weeks of gestation. The major ﬁndings include poor visualization of the bladder, a lower abdominal bulge, small genitalia (in males), a low-set umbilicus, and a pubic bone diastasis. If the diagnosis is not established before birth, it is readily apparent upon delivery.
Immediately after birth, the umbilical cord should be tied with a ligature rather than clamped with plastic or metal, so as to minimize trauma to the exposed bladder mucosa. Likewise, a sheet of plastic wrap should be used to cover the anterior abdominal defect and protect the bladder mucosa from abrasion by towels, diapers, and clothing. A thorough physical and radiologic assessment should be performed to assess for the presence of other anomalies.
The relative merits of a single or staged repair of the exstrophy, epispadias, abnormal ureterovesical junctions, and abnormal bladder neck have yet to be determined; however, it is clear that the sooner the exstrophied bladder is closed and the bladder neck and sphincter are reapproximated, the better the chance for a functional bladder and long-term urinary continence.
The timing of the initial closure depends on a number of variables, including the size of the bladder, the size of the penis in the male patient, the length and depth of the urethral groove, the width of the pubic diastasis, and the presence or absence of other associated anomalies. Most exstrophies, however, can be closed within the ﬁrst 72 hours of the infant’s life, which protects the bladder mucosa from the environment and facilitates development of the bladder musculature. At the time of the initial closure, many patients also undergo pelvic osteotomy in which the ilia and ischia are cut to facilitate reapproximation of the pubic symphysis. This procedure can reduce tension on the abdominal wall closure, and it reapproximates the pelvic ﬂoor musculature in the midline to improve later continence. Whether osteotomy is performed or not, the infant’s pelvis is usually immobilized for up to 1 month after the procedure to facilitate normal bone alignment.
With current reconstructive strategies, most patients achieve urinary continence (albeit with clean intermittent catheterization in a signiﬁcant proportion) and can lead satisfying personal and professional lives. Long-term management, however, must address the psychological effects of this condition, possible sexual dysfunction (especially in women), and later complications, such as vaginal and rectal prolapse in women.