Bladder, Urethra, and Cloacal Exstrophy Flashcards
What anomalies make up the spectrum of the Exstrophy-Epispadias complex?
- Epispadias: The urethra is a partial or complete open plate on the dorsal penis. There is always severe dorsal chordee and it can be associated with vesico-ureteric reflux (VUR) and urinary incontinence.
- Classic bladder exstrophy (CBE): There is pubic diastasis with subsequent diastasis of the anterior abdominal wall. The bladder is an open plate often associated with congenital pseudo-polyps and it is incarcerated within the abdominal defect in an extraperitoneal position. The umbilical cord is usually lower in the abdomen compared to normal children. It is always associated with epispadias and the length of the urethral plate represents a critical factor in the reconstruction.
- Cloacal exstrophy (CE): It is one of the most severe congenital malformations compatible with life. Over 70% of the patients have severe associated anomalies including spinal dysmorphism and limbs abnormalities. There is extreme pubic diastasis and an omphalocele which both contribute to a large anterior abdominal wall defect. Two hemi-bladders are incarcerated in the abdominal defect and between them there is the cecum which is opened, and the ileum prolapses through the defect like an elephant trunk.
- Exstrophy variants: Partial manifestations of the above anomalies, which may lack symmetry in the sagittal plane.
There is significant variability of clinical manifestations and it is imperative to rule out associated anomalies.
Which embryological structure is commonly implicated in the pathogenesis of exstrophic anomalies?
• The cloacal membrane.
By the 4th week of gestation, the cloacal membrane forms the ventral wall of the urogenital sinus.
With further development, mesoderm fuses in the midline to form the lower abdominal wall with simultaneous caudal progression of the urorectal septum to separate the cloaca into the urogenital canal and rectum.
The Marshall and Muecke’s theory states that rupture of the cloacal membrane after complete separation of the GU and GI tracts results in CBE and prior to descent of the urorectal septum results in CE.
Epispadias occurs when there is failure of midline mesodermal fusion of the most distal part of the anterior cloacal membrane.
Normally the bladder forms around the 4th–8th week of gestation and represents the most anterior lower abdominal organ.
The two hemi-bony-pelvises form laterally to the sacrum and subsequently start to internally rotate which completes around the 10th week of gestation with the formation of the pubic symphysis.
The Cervellione’s theory speculates that the bladder remains trapped between the two pubic bones during their migration to the midline and the detrusor fuses to the pubic bones and the lower abdominal wall leading to perforation of the bladder.
The positive intra-abdominal pressure inverts the bladder ‘inside- out’.
The corpora cavernosa remain attached to the pubic bones and cannot externally rotate as normally happens with the consequent dorsal chordee.
What is the risk of recurrence of exstrophy in the family of a known index case?
Current counselling recommendations:
• 1% sibling recurrence
• 1:70 chance of transmission from parent to child.
What is the prevalence of CBE, CE, and epispadias?
The following figures are according to a recent European prospective trial [5]:
• Male epispadias ~1 in 101,000
- Female epispadias ~1 in 1,300,000
- CBE ~1 in 46,000. M:F 3:1
- CE ~1 in 317,000. M:F 6:1.
What is the rate of associated anomalies in CBE, CE, and epispadias?
- Epispadias ~3%: renal, chromosomal [5]
- CBE ~5%: renal, chromosomal, cardiac, anorectal malformation[5]
- CE ~71%: Gastrointestinal 65% (malrotation, short gut, duodenal atresia), Sacral agenesis 60%, spinal dysraphism 50%, orthopaedic 40% (club foot, hip dysplasia), cardiovascular <10%, and renal anomalies 7% (ectopic kidney, agenesis).
What antenatal ultrasound findings suggest a diagnosis of an exstrophy- epispadias complex?
- Failure to visualize the bladder (usually visible at ~14 weeks gestation)
- Lower abdominal wall mass
- Low-set umbilical cord
- Abnormal genitalia
- Widening of the iliac crests.
Data suggests that approximately 25% of bladder and cloacal exstrophy patients are detected antenatally [5].
What are the key external characteristics of CBE in male and female patients?
The bladder is open on the lower abdominal wall and the urothelium fully exposed. In males, the penis is short and wide with a short urethral plate and a dorsal chordee.
In females, the clitoris is bifid with the labia displaced laterally.
The vagina is displaced anteriorly and the mons pubis is absent.
In both sexes, the pubic symphysis is widely separated with divergent recti muscles.
What is the rate of inguinal hernias in patients with bladder exstrophy?
> 80% males >10% females.
Indirect inguinal hernias are commonly associated with bladder exstrophy [1, 2].
The wide pubic diastasis and external rotation of the anterior pelvis means that the internal and external rings lie in an anterior-posterior plane rather than the usual oblique plane seen in non-exstrophy children.
In addition to ligation of the patent processus vaginalis (PPV), what additional step must be undertaken during inguinal hernia repair in exstrophy patients?
• Narrowing of the internal ring.
This operative step, incorporating simple absorbable sutures, reduces the hernia recurrence rate.
Care must be taken to not strangulate the spermatic cord.
A term baby is born with CBE and is awaiting operative repair. What pre-operative measures must be taken during this period?
A hydrated gel dressing or plastic wrap is secured over the bladder and changed daily with normal saline irrigation.
Parents must be warned about the possibility for the baby to develop an inguinal hernia and occasionally rectal prolapse.
Patients with CBE often have no life-threatening anomalies and should be encouraged to remain with their recovering mothers until surgical repair is planned.
Feeding need not be restricted and breast-feeding encouraged.
Antibiotic prophylaxis is usually not required.
Pre-operative renal ultrasound is necessary to rule out upper tract dilatation and as a baseline for future ultrasound studies.
Spinal ultrasounds are necessary to rule out spinal cord anomalies.
In CE, an echocardiogram is always needed due to the higher rate of cyanotic heart disease (<10%) [1].
Antibiotics are also needed peri-operatively.
What are the pathological hallmarks of exstrophic bladders?
Exstrophic bladders demonstrate a similar amount of type 1 collagen but a 3-fold increase in type 3 collagen compared to controls [6].
Patients with adequate bladder capacity post closure demonstrate a significant decrease in the ratio of collagen to smooth muscle, provided the bladder remained infection free [6].
Based on experimental studies, exstrophy patients have similar cholinergic receptor density and binding affinity, but a significant decrease of myelinated nerves per field [6].
What are the key external characteristics of CE?
There is a central hind-gut plate with two separated bladder halves.
The ileum intussuscepts through the ileocaecal valve and into the hindgut creating an elephant trunk appearance.
One or two appendices may be seen on either side of the ileum.
Pubic diastasis is almost twice that seen in children with classic exstrophy and the two phallic halves may be completely separated and asymmetrical with a dominant hemiphallus or hemiscrotum.
Patients with CE almost always required pelvic osteotomies for proper pelvic closure.
The anus is imperforate, sacrum short, and spinal dysraphism may be evident. There is usually an associated omphalocele (>88%) [1].
What are the main operative approaches to anatomic reconstruction?
a. Primary versus staged
b. Early versus delayed.
The author’s surgical preference is the Manchester delayed exstrophy closure technique.
This staged approach involves initial bladder closure with ureteric re-implantation at 3–9 months followed by epispadias repair at 12–18 months.
In this approach, further bladder neck surgery or bladder augmentation may or may not be necessary at 5–6 years depending on continence outcomes and only after vigorous biofeedback training.
The complete primary repair (Mitchell technique) includes bladder closure, urethroplasty, and genital reconstruction. Due to penile ischaemic complications, this technique should be considered obsolete.
However, a modification of the technique with a less aggressive penile dissection is still adopted in some centres in North America.
What are the main components of the staged closure technique?
a. Bladder closure with ureteric re-implantation and tubularisation of the proximal urethra at 3–9 months of age with pelvic osteotomies and insertion of a pelvic external fixator
b. Epispadias repair (12–18 months)
c. Potty training and biofeedback between the age of 3 and 5 years
d. ± Bladder neck reconstruction (~6 years) if continence not attained after bio- feedback training
e. ± Bladder augmentation if small non-compliant high pressure bladder.
What is the sequence of reconstruction in CE patients?
- Initial management of the associated anomalies and prematurity when appro- priate. Severe lung hypoplasia may require prolonged ventilation after birth and occasionally can be fatal.
- If a large omphalocele is present, gradual reduction of the omphalocele is performed in the NICU suspending the umbilical cord to the roof of the incubator to facilitate the descend of the liver into the abdominal wall.
- First stage of reconstruction is performed when the baby is stable, usually in the first few weeks of life:
a. Insertion of central line for parenteral nutrition (PN)
b. Laparotomy with Ladd’s procedure if required
c. Separation of the cecum from the hemi-bladders, tubularisation of the cecum
after washout of the atretic colon and formation of an ileostomy
d. The two hemi-bladders are sutured together
e. The omphalocele is reduced when possible. - Bladder closure with para-exstrophy skin flaps to reconstruct the absent urethra with pelvic osteotomies is performed when the patients is about 6–7 kg.
What are the advantages of performing pelvic osteotomies at the time of initial bladder closure?
• Facilitates closure of the pubic symphysis
• Decreased abdominal wall tension and reduced risk of wound dehiscence
• Placement of bladder and urethra deep within the pelvis
• Increased pelvic floor support around the bladder neck which may improve
future continence.
Studies have shown that exstrophy patients tend to have shorter pubic bones than controls [7].
Although this was originally been thought to be a congenital phenomenon, recent evidence shows that this is an acquired condition resulting from the lack of tension across epiphyseal plates in an incomplete pelvic ring and epiphyseal plate damage following osteotomy [7].
Tension across epiphyseal plates has been shown to increase bone growth [7].
Incision of what anatomic structure is essential to move the bladder and urethra posteriorly in the pelvis?
• The intersymphyseal bands: This structure represents part of the anterior detrusor abnormally attached to the medial portion of the pubic bones.
Failure to divide the intersympheseal bands does not allow positioning of the bladder deep in the pelvis and appropriate securement of the pubic bones in the midline.
What is the most common complication following exstrophy closure?
The most commonly reported complication is a urethrocutaneous fistula (5–40%), commonly in the peno-pubic angle in males [2].
Since they may close spontaneously, they can initially be managed conservatively via catheter drainage.
If the fistula does not close, cystoscopy must be performed to evaluate for possible bladder neck obstruction.
Wound dehiscence is associated with increased tension on the wound and may be reduced with pelvic osteotomies.
Complete breakdown of the repair is rare and usually associated with severe infection or technical errors.
What is the incidence of vesico-ureteric reflux (VUR) following exstrophy closure?
Small bladder size, increased detrusor pressures, and increased outlet resistance following closure results in VUR in almost all patients.
Moreover, the ureters often enter the bladder with a short submucosal tunnel predisposing to reflux.
For this reason, the authors prefer to perform ureteric reimplantations in all patients at the time of primary bladder closure.
Following closure, patients must be followed closely with 3–6 monthly ultrasound scans to look for any signs of upper tract deterioration.
Progressive dilatation, especially when associated with urinary tract infections, may require a period of anticholinergics, intermittent catheterization and eventual bladder augmentation to reduce bladder pressures and protect the upper tracts.
A 35-year old woman born with classic bladder exstrophy underwent a ureterosigmoidostomy in childhood for urinary diversion. What are the long-term complications of this procedure?
Continent and incontinent urinary diversion techniques (i.e. Indiana pouch, uret- erosigmoidostomy, ileal conduit) have largely been abandoned in favour of anatomic reconstruction.
However, these procedures may be useful to achieve dryness in patients who have failed multiple attempts at anatomic reconstruction.
Long-term complications associated with ureterosigmoidostomy [2]:
- Hyperchloremic metabolic acidosis
- Chronic pyelonephritis
- Bladder calculi
- 250–300-fold increased risk of adenocarcinoma at the anastomosis.
Any attempt at reversal of a ureterosigmoidostomy must include excision of a cuff of normal colonic tissue at the site of the implanted ureters to prevent future malignancy [2].
A concerned mother asks you about her daughter’s fertility poten- tial after undergoing a successful staged exstrophy closure. How do you respond?
In contrast to males, most females have normal fertility [8].
Women must have an elective caesarean section to avoid injury to the reconstructed urinary tract.
In addition, females often have normal sexual desire, are adequately sexually active, and have normal menstruations [8].
However, the vagina is often short and verti- cally lying, which may require an introitoplasty or vaginoplasty in adulthood to allow normal sexual intercourse.
Uterine prolapse is a common occurrence (30– 60%) and may be precipitated by pregnancy [8].
In cases of refractory prolapse, complex uro-gyne reconstruction may be required.
In males, fertility potential is significantly reduced and normal sperm counts are reported in 16–63% of patients [8].
The volume of ejaculate of often low and up to 50% experience retrograde ejaculation [8].
The effect on fertility potential is likely attributed to previous bladder neck surgery.
Although the penile length is short, most male patients have normal libido and erections adequate for sexual function [8].
What are the psychosocial outcomes following exstrophy closure?
Both males and females suffer from psychosocial disturbances due to body image and genital perception.
Exstrophy patients have higher rates of anxiety, depression, and suicidal ideation than controls [8].
Therefore, early psychiatric assessment and parental education is warranted.
What is the exstrophy-epispadias complex (EEC)?
The exstrophy–epispadias complex (EEC) is a spectrum of embryologic abnormalities.
Diagnoses within the EEC range in severity from those involving only one organ to others that are a part of a larger complex of defects. The spectrum includes:
□ Epispadias—the urethra is a partial or completely open “plate” dorsally on the penis or between the clitoral halves in a girl.
□ Classic bladder exstrophy (BE)—the urinary bladder is an open plate on the lower abdomen, always associated with epispadias.
□ Cloacal exstrophy (CE)—in which the bladder and the ileocecal junction of the bowel are an open plate on the lower abdomen, and the hindgut is truncated and terminates in the perineum. This condition is also known as the omphalocele/exstrophy/imperforate anus/spinal defect (OEIS) complex.
□ Exstrophy variants—in which partial manifestations of the above anomalies are seen and commonly lack symmetry in the sagittal plane.
H&A
What are common alterations in the anatomy of patients with bladder exstrophy?
Classic BE occurs in approximately one per 50,000 live births, with about an equal incidence in males and females.
CE is rarer with an incidence of 1 in 300,000.
Since the 19th century, various efforts to manage BE have been described.
Because the condition is rare, these approaches were empiric and usually unsuccessful. Until the 20th century, there was no effective surgical approach.
Even now, optimal management is elusive and surgical reconstruction may require multiple operations.
Children with BE typically have an anteriorly located anus.
Also, the female genital anatomy is altered with a more vertically oriented vaginal opening following repair, and a wider and shorter vagina than normal.
The anterior component of the penis is also foreshortened in males compared with the general population.
Classic BE, however, is rarely associated with other organ system malformation.
H&A
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In general infants with bladder exstrophy are born full term, without coexisting anatomic anomalies.
At birth, an everted posterior bladder plate of varying size is seen in the midline of the lower abdomen. The mucosa of the exposed bladder in the newborn is typically smooth and pink.
The umbilical cord exits from the superior-most border of the bladder plate, and a small umbilical hernia may be present.
In addition, there is significant widening of the pubic symphysis and the anus is anteriorly displaced.
The levator ani complex is also divergent, leading to an inherent weakness in the pelvic floor and a tendency toward rectal prolapse and varying degrees of fecal incontinence.
Associated inguinal hernias are common and have been reported in 82% of boys and 10% of girls.
The upper urinary tract is usually normal, though renal anomalies including ectopic, horseshoe, hypoplastic, dysplastic kidneys, and megaureters may be observed.
Vesicoureteral reflux occurs in the vast majority of children after bladder closure, secondary to an exaggerated lateral course of the ureters within the pelvis and lack of adequate submucosal tunnel in the bladder wall.
With continued exposure and chronic inflammation, the exstrophied bladder becomes thickened and polypoid. Long-term exposure may eventually result in a fibrotic, rigid bladder plate that is ultimately unsuitable for closure.
GENITAL DEFECTS—MALE
In the male infant, the open and everted urethral plate can be seen joining the exposed bladder.
The penis is characteristically short with a flattened, everted glans.
The prepuce is located on the penile ventrum.
The ejaculatory ducts are typically normal and exit at the exposed verumontanum in the posterior urethra.
The base of the penis and scrotum are widely separated, with lateral displacement of the corporal bodies and neurovascular bundles.
Historically it was believed that the individual corpora were of normal caliber and appeared shortened because of their attachment to the widened pubic diastasis and associated dorsal chordee.
More recently, an MRI-based study by Silver and colleagues of adult men with exstrophy and age-matched controls found that although the length of the posterior corporal bodies was the same between groups, anterior corporal length in men with exstrophy was nearly 50% shorter than that of controls.
Therefore the penis appears shortened not only secondary to corporal divergence, dorsal chordee, and abnormal crural attachments to the corpora cavernosa, but also because of an inherent deficiency of corporal tissue.
The testes may appear to be undescended, but in most cases they are actually retractile and will eventually reside in the scrotum without the need for formal orchiopexy.
Should it be required, orchiopexy is performed in conjunction with inguinal hernia repair.
GENITAL DEFECTS—FEMALE
The clitoris is bifid, with divergence of the mons pubis, labia, and clitoral halves.
The urethra and vagina are shortened, and the introitus is anteriorly displaced.
The vaginal orifice is often stenotic.
The uterus and adnexa are typically normal, though vaginal and uterine duplication have been reported.
Uterine prolapse occurs commonly in female patients, secondary to the inherent weakness in pelvic floor support.
PELVIC DEFECTS
Some degree of widening of the pubic symphysis is present in all cases of bladder exstrophy and contributes to outward rotation and eversion of the pubic rami at their junctions with the ischial and iliac bones.
Using computed tomography (CT), Sponseller and colleagues further characterized the pelvic anatomy of a large group of exstrophy patients, noting a significantly increased distance between the triradiate cartilages (31%), external rotation of the anterior pelvis (18%), and 30% shortening of the pubic rami.
On the basis of three-dimensional models generated by CT, Stec and colleagues observed that among children with exstrophy, the levator ani muscles were more posteriorly positioned and outwardly rotated.
Furthermore, the puborectal sling had a more flattened configuration and supported twice the body cavity area in exstrophy patients.
As mentioned previously, these pelvic floor defects predispose to pelvic organ and rectal prolapse in this patient population.
Coran