Jason C. Fisher, MD
Harry P. Koo, MD, FAAP, FACS
BASICS
DESCRIPTION
• Cloacal exstrophy, or vesicointestinal failure, is a congenital abnormality of the infraumbilical abdominal wall. Its presentation is highly variable, but key features include an exomphalos with an exstrophied cecum flanked by two hemibladders
• Ureteral orifices present on each hemibladder. Cecal plate has orifices to three structures:
– Appendix
– Blind-ending hindgut (colonic remnant)
– Ileum, often prolapsed elephant-trunk deformity
• Most severe anomaly along epispadias–exstrophy complex (EEC) spectrum
• When neurospinal defects and omphalocele occur with cloacal exstrophy, it is termed OEIS complex (omphalocele, exstrophy, imperforate anus, spinal defects)
EPIDEMIOLOGY
Incidence
• One of the rarest urologic anomalies
• Widely quoted historic incidence of 1:200,000 to 1:400,000 based on statistical estimates
• More accurate and contemporary international registries now estimate 3:100,000 to 8:100,000.
• Male ≥ Female (1:1–2:1)
RISK FACTORS
• No well-defined causative factors; statistical analysis of large registries identifies the following:
– Bimodal risk of maternal age: <20 year old or >30 year old
– Intrauterine fet al demise of twin pregnancy
– In vitro fertilization
Genetics
• Most cases are sporadic
• Some cases reported with genetic causation:
– Unbalanced translocation of 9q and Yq
– Homeobox mutations at HLXB9 and HOX
PATHOPHYSIOLOGY
• Traditionally postulated embryologic theories:
– Premature cloacal membrane rupture (8 wk)
– Failed cloacal partition by lateral folds of Rathke
– Incomplete descent of a cloacal septum
• Current understanding of cloacal exstrophy embryogenesis (1)[B]:
– Disrupted cellular proliferation and apoptosis of dorsal cloacal wall and infraumbilical mesenchyme—this disrupts the infraumbilical body wall, everts the cloacal cavity, and wedges the pubic bones and genital tubercles apart
ASSOCIATED CONDITIONS
• Upper genitourinary anomalies:
– Unilateral renal agenesis (33%)
– Pelvic kidney (33%)
– Hydronephrosis (33%)
– Horseshoe kidney
– Fusion anomalies
– Ureteral anomalies
• Lower genitourinary anomalies:
– Separation or absence of clitoral/phalic halves
– Separation of scrotum or labia
– Undescended testicles/bilateral hernias
– Uterine and vaginal duplication anomalies
• Gastrointestinal anomalies:
– Omphalocele (88–100%)
– Short-gut (25%; source of major morbidity)
– Intestinal malrotation
– Intestinal duplication
– Imperforate anus/anal atresia
• Central nervous system anomalies:
– Tethered spinal cord
– Myelomeningocele
– Aberrant pelvic autonomic nerve anatomy
– Impaired continence, ambulation, erectile function
• Musculoskelet al anomalies:
– Symphysis pubis diastasis
– Sacral dysplasias and vertebral anomalies
– Scoliosis
– Hip subluxation and acetabular dysplasia
– Lower limb anomalies
• Serious cardiovascular and pulmonary anomalies are uncommon with cloacal exstrophy
DIAGNOSIS
Cloacal exstrophy is a major congenital anomaly. Prompt referral and coordination with a variety of specialists including pediatric urology, pediatric general surgery, pediatric orthopedics, neonatology, pediatric gastroenterology, pediatric neurosurgery, endocrinology, genetics, and social work is needed.
HISTORY (ANTENATAL)
• Major diagnostic criteria (2)[A]:
– Nonvisualization of the bladder (91%)
– Large midline infraumbilical anterior abdominal wall defect or cystic anterior abdominal wall structure (82%)
– Omphalocele (77%)
– Lumbar myelomeningocele (68%)
• Prolapsed ileal segment can be pathognomic
PHYSICAL EXAM
• The classic collection of findings include:
– Exstrophy of the bladder
– Complete phallic separation
– Wide pubic diastasis
– Cecal plate everted between 2 hemibladders
– Blind-ending hindgut; no well-formed colon
– Omphalocele
• Thorough assessment for associated anomalies (see “Associated Conditions”):
– Spinal and vertebral defects
– Lower extremity malformations
– Patency and position of anus
– Presence of descended testicles
• Detailed exam of exstrophy:
– Males: Divided corpus cavernosum and glans
– Females: Divided clitoris, duplicated vagina
– Additional müllerian anomalies
– Identification of ureteral orifices: Two exstrophied hemibladders are on either side of the exstrophied intestinal segment. Each half usually drains the ipsilateral ureter
– Identification of intestinal orifices: Appendix, hindgut, ileum (often prolapsed)
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Karyotype
• CBC, basic metabolic panel:
– At risk for nongap metabolic acidosis due to absorption of urine chloride by intestinal mucosa
– Type and cross blood for surgery
Imaging
• Plain CXR, sacral and spinal x-rays
• Ultrasounds of abdomen, kidneys, head, spine
• Consider MRI to detect occult spinal lesions if no obvious dysraphism and US nondiagnostic
• Skelet al and bony films of pelvis and lower extremities as needed
• Echocardiogram: Low incidence of associated cardiac lesions, but advisable in the preop setting
DIFFERENTIAL DIAGNOSIS
• Unique appearance makes it unlikely to confuse with other conditions
• Exists along EEC spectrum
• Consider isolated bladder exstrophy, giant isolated omphalocele, large epispadias
TREATMENT
GENERAL MEASURES
• Assessment of newborn with anomaly:
– Immediate cardiopulmonary stabilization
– Neonatology management of prematurity
– IV access: UA and UV lines not possible
• Protection and prevention maneuvers:
– Ligate umbilical cord with silk tie (avoid plastic clip which will irritate bladder mucosa)
– Lower half of infant in bowel-bag initially
– Cover exstrophic tissue with plastic wrap
– Protect omphalocele: Minimal handling
– Assess for open spinal cord defects
– Place nasogastric tube for decompression
– Prophylactic antibiotics (ampicillin and gentamicin)
• Contact specialists (see under “diagnosis" heading above) immediately.
• Detailed exam to assign gender
– Identification of phallus, labia/scrotum, testes
– Consistent with the karyotype if possible
MEDICATION
First Line
• IVF support: Adjust for fluid losses across exstrophied mucosa
• At risk for hyperchloremic metabolic acidosis
• Generally not candidates for epidural anesthesia due to spinal dysraphism
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Open spinal anomaly: Prompt neurosurgical repair required before addressing exstrophy.
• Exstrophy repair at 48–72 hrs of life if stable
– Combined pediatric urology and general pediatric surgery
– Usually staged approach vs. single stage
• Multistage approach (3)[B]: Creates classic bladder exstrophy anatomy at conclusion of initial surgery described above; preferred for most cases. General principles of Stage 1:
– Separate hemibladders from cecal plate
– Revert any prolapsed terminal ileum
– Mobilize, rescue, and preserve any hindgut
– Tubularize the cecum to bring terminal ileum, cecum, and hindgut into closed continuity
– Create end colostomy from distal hindgut
– Assess and preserve müllerian anatomy
– Excise and close omphalocele if possible
– Anastomose hemibladders in midline
• Single-stage approach (4)[B]: In highly select patients, can proceed with bladder and abdominal wall closure and phallic reconstruction which may avoid osteotomies, minimize bladder scarring. Otherwise, Stage 2 is performed in late infancy, mirroring a classic bladder exstrophy repair:
– Mobilize bladder plate and posterior urethra deep into pelvis: Yields incontinent bladder.
– Orchiopexy with repair of inguinal hernias
– Reconstruct gender-based external genitalia
– Pubic reapproximation +/– pelvic bone osteotomies with fixation and traction for 4–6 wk
• Stage 3 involves procedures aimed at continence and genital cosmesis and is addressed in older children, often involving bladder augmentation and catherizable conduits
• Surgical pitfalls to avoid:
– Injury to ureteral orifices: Place stents
– Overaggressive closure of a large omphalocele defect leading to compartment syndrome
– Excising/discarding diminutive male phalic remnants and assigning female gender: Controversial and still occurs with unclear long-term consequences
– Excising/discarding the hindgut even if short
– Primary perineal pull-through of the hindgut (can be performed in highly select patients)
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Large omphaloceles not amenable to primary closure can be treated with Silvadene-mediated epithelialization of sac followed by delayed closure, or by excision of sac and placement of a silo with gradual staged reduction of viscera
• Consider gastrostomy tube placement and/or tunneled central line during initial repair if patient appears at risk for short-gut syndrome
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Survival >90% over last 20 yr
• Nutrition and growth is the most important determinant of early survival and morbidity
– 30–50% will have failure to thrive before age 5
– Important to avoid using any bowel for GU reconstruction procedures until child is thriving
• After 3 yr, quality-of-life issues outweigh nutritional concerns
– Urinary continence: Rarely achieved; dependent on a compliant reservoir and continent catherizable conduit
– Fecal continence: Usually managed by enema regimen, rarely are perineal pull-through maneuvers associated with any continence
– Gender assignment and reconstruction, especially for genetic males raised as females
– Ambulation impairments
– Gynecologic issues after onset of menarche
– Psychosexual problems
COMPLICATIONS
• Infection and breakdown of repair
• Abdominal compartment syndrome
• Short-gut syndrome
• Vesicoureteral reflux and hydronephrosis
• Hirschsprung-type enterocolitis in the dysmotile hindgut, even after colostomy formation
FOLLOW-UP
Requires a multidisciplinary team (see “Diagnosis”) to coordinate regular follow-up through all stages of surgical repair, with careful attention to nutrition and growth in infancy, and both surgical and psychological support for the multiple quality of life issues which begin in childhood and persist into adulthood
Patient Resources
Urology Care Foundation. http://www.urologyhealth.org/urology/index.cfm?article=91
REFERENCES
1. Vermeij-Keers C, Hartwig NG, van der Werff JF. et al. Embryonic development of the ventral body wall and its congenital malformations. Semin Pediatr Surg. 1996;5:82–89.
2. Austin PF, Homsy YL, Gearhart JP, et al. The prenatal diagnosis of cloacal exstrophy. J Urol. 1998;160:1179–1181.
3. Stolar CH, Randolph JG, Flanigan LP. Cloacal exstrophy: Individualized management through a staged surgical approach. J Pediatr Surg. 1990;25:505–507.
4. Zderic SA, Canning DA, Carr MC, et al. The CHOP experience with cloacal exstrophy and gender reassignment. Adv Exp Med Biol. 2002;511:135–147.
ADDITIONAL READING
• Mathews R, Jeffs RD, Reiner WG, et al. Cloacal exstrophy: Improving the quality of life: The Johns Hopkins Experience. J Urol. 1998;160:2452–2456.
• McHoney M, Ransley PG, Duffy P, et al. Cloacal exstrophy: Morbidity associated with abnormalities of the gastrointestinal tract and spine. J Pediatr Surg. 2004;39:1209–1213.
• Reiner WG. Psychosexual development in genetic males assigned females: The cloacal exstrophy experience. Child Adolesc Psychiatric Clin N Amer. 2004;13:657–674.
• Soffer SZ, Rosen NG, Hong AR, et al. Cloacal exstrophy: A unified management plan. J Pediatr Surg. 2000;35:932–937.
See Also (Topic, Algorithm, Media)
• Epispadias
• Exstrophy–Epispadias Complex
• Exstrophy, Bladder (Classic Exstrophy)
• Exstrophy, Cloacal Images 
CODES
ICD9
753.5 Exstrophy of urinary bladder
ICD10
Q64.12 Cloacal extrophy of urinary bladder
CLINICAL/SURGICAL PEARLS
• Meticulous assessment of associated anomalies can prevent early clinical and surgical mishaps, particularly with regard to spinal defects.
• A multidisciplinary team is critical to the short- and long-term outcomes of these children.
• A staged surgical repair remains the preferred approach for most children with cloacal exstrophy.
• Do not underestimate the impact of early gender assignment: Avoid irreversible surgical resection of structures that may be useful for genital reconstruction.
• Save as much bowel as possible, especially the short hindgut, to maximize nutritional capability.