A male newborn was delivered vaginally at 385/7 weeks. Pregnancy was uneventful, and no fetal anomalies were detected at prenatal ultrasound controls. Maternal serologies for HbsAg, HCV, HIV, Toxoplasma, and Rubella were negative, as was vaginal swab. Delivery was not complicated and Apgar Score was 9 at 1st, 9 at 5th, and 10 at 10th minute of life. The neonate presented at birth with a genitourinary defect consistent with the classic bladder exstrophy variant of the exstrophy–epispadias complex (EEC). Exposed, everted bladder template was clearly visible immediately below umbilical stump; a completely dorsally opened (epispadic) urethral plate run from bladder neck down to the open glans; left and right corpora cavernosa were clearly visible beneath and alongside urethral plate; the scrotum was normally developed, but caudally displaced; anus was normal ([Fig. 1]). Physical examination was otherwise unremarkable. The defect was covered in delivery room with sterile silicon gauzes and transparent waterproof dressing. Prudently, no umbilical vascular catheters were positioned at birth. Cerebral, cardiac, abdominal, and kidney ultrasound were then performed, turning out to be normal. Pelvic ultrasound esteemed a pubic symphysis diastasis of 28 mm. At 72 hours of life, primary closure of bladder, pelvis, and abdominal wall was performed successfully, without pelvic osteotomy. Two ureteral catheters, one transurethral catheter and an epicystostomy tube were left indwelling. In the first 5 postoperative days, the patient was kept immobilized with pelvis and lower limbs wrapped around and suspended in a special hammock device (modified Bryant traction) ([Fig. 2]).[1] Parenteral nutrition was administered during this period. Curarization was maintained for the first 5 days after surgery; systemic sedoanalgesia was gradually tapered, and ultimately stopped 10 days after surgery. Full enteral feeding was restored at day 10 postoperatively. A perirenal urinoma was registered as a postoperative complication. Tubes were sequentially removed during the fourth postoperative week, and patient was discharged on postoperative day 28. Patient was kept in a thoracopelvic orthosis for the first 2 month of life.[2] Further surgery for epispadias repair is scheduled at the age of 9 months of life.
Fig. 1 Male newborn with classic bladder exstrophy. Exposed, everted bladder template is clearly visible immediately below umbilical stump; a completely dorsally opened (epispadic) urethral plate runs from bladder neck down to the open glans; left and right corpora cavernosa are visible beneath and alongside urethral plate; the scrotum is caudally displaced.
Fig. 2 Postoperative patient immobilization with pelvis and lower limbs wrapped around and suspended in a special hammock device (modified Bryant traction).
Discussion
What is Exstrophy–Epispadias Complex
EEC encompasses a spectrum of pathologies going from isolated epispadias, to classic bladder exstrophy, to cloacal exstrophy as the most severe—and rarest–presentation.[3] Next to the bladder, the malformation involves the genitalia, the abdominal wall muscles, the pelvic floor musculature, and the bony pelvis.[4]
Epidemiology
The overall incidence of EEC has been estimated by Nelson et al[5] in 2.15 per 100,000 live births, with an even male-to-female ratio (odds ratio, 0.989; 95% confidence interval 0.88–1.12), and a significantly increased incidence in white compared with nonwhite neonates (incidence, 2.63 vs. 1.54 per 100,000; p < 0.0001). Classic bladder exstrophy occurs in 1:10,000 to 1:50,000 live births[6]; epispadias is estimated to occur in 1:117,000 live births, and cloacal exstrophy in 1:250,000 births.[7]
Embryology and Associated Conditions
EEC derives from a derangement in mesodermal layers fusion during the first weeks of fetal life. Normally, at the end of third week of gestation, intermediate layer of mesoderm starts to invaginate to give origin to the urogenital system, while the lateral plate mesoderm will contribute in forming the primitive gut tube.[3] A disruption in this interaction, possibly related to a cloacal membrane overgrowth preventing medial migration of mesenchymal tissue, is reported to give origin to EEC[8]; severity of the resulting condition depends on the point at which disturbed mesodermal layers interaction begins.
Given the embryological origin of the disorder, EEC is often associated with other peculiar orthopedic, musculocutaneous, and gynecological conditions. Associated upper urinary tract anomalies are rare. Gastrointestinal and spinal/neurological anomalies can be associated in patients with cloacal exstrophy ([Table 1]).[3]
[4]
[9]
Table 1
EEC—commonly associated conditions
|
Urological
|
|
Stenosis/obstruction of the ureteropelvic junction
|
|
Vesicoureteral reflux
|
|
Ectopic kidney
|
|
Horseshoe kidney
|
|
Renal dysplasia/agenesis
|
|
Megaureter
|
|
Ureteral ectopy
|
|
Ureterocele
|
|
Musculocutaneous
|
|
Abdominal wall defects
|
|
Divergent distal rectus abdominis muscles
|
|
Umbilical hernia
|
|
Spinal/neurological
|
|
Neural tube defects
|
|
Vertebral anomalies
|
|
Myelodysplasia and/or myelomeningocele
|
|
Dysraphism
|
|
Tethered cord
|
|
Orthopedic
|
|
Clubfoot deformities
|
|
Absence of feet
|
|
Tibial or fibular deformities
|
|
Hip dislocations
|
|
Pubic symphysis gap
|
|
Open-book configuration of the pelvis
|
|
Gastrointestinal
|
|
Common hindgut remnant
|
|
Anteriorly displaced anus
|
|
Imperforate anus
|
|
Rectal stenosis
|
|
Rectal prolapse
|
|
Omphalocele
|
|
Gastrointestinal malrotation/duplication
|
|
Short bowel syndrome
|
|
Duodenal atresia
|
|
Small short bowel deletion
|
|
Gynecological
|
|
Vaginal/uterine prolapse
|
|
Müllerian anomalies (e.g., vagina and/or uterus duplication, vaginal agenesia)
|
Abbreviation: EEC, exstrophy–epispadias complex.
Medical and Surgical Management
Immediate medical management of EEC consists of covering the extruding viscera with sterile silicon gauzes plus a surmounting occlusive dressing to prevent air contact and dehydration of the exstrophic plaque. Umbilical catheters should not be positioned. No prophylactic antibiotic therapy is mandatory at birth if no physical signs of infection are detectable; on the contrary, postoperative prophylactic antibiotic treatment is advisable to avoid potential postoperative complications (see section “Long-Term Complications and Outcome”).
Surgical correction varies depending on the type and severity of the defect; most of the neonates, however, will need closure of the bladder and abdominal wall, repair of epispadias, ureteral reimplantation, and bladder neck repair. Some of them will also require pelvic osteotomy to facilitate relaxation of the abdominal wall during closure. Osteotomy might possibly also improve functional outcomes of genitourinary reconstruction.[10] Criteria proposed to select cases requiring an osteotomy include patients undergoing closure after 72 hours of life, when the pelvis becomes more stiff, those with a pubic diastasis wider than 4 cm, and those with a nonmalleable pelvis. Under these circumstances, the osteotomy is performed at the same time as exstrophy closure (i.e., combined pelvic osteotomy).[11] In patients with extremely wide pubic diastases (> 6 cm, most often associated with cloacal exstrophy), a strategy involving osteotomy before bladder closure (i.e., staged pelvic osteotomy) has been proposed to allow gradual reduction in diastasis with slow stretching of pelvic soft tissue.[12]
Postoperatively, management key factors for the success of closure include immobilization and traction of the lower limbs, appropriate urinary drainage, curarization, analgesia (also using epidural catheters when possible), broad-spectrum antibiotic prophylaxis, and parenteral nutrition.
Currently, a staged approach is the strategy most commonly used. Alternatively, the neonatal primary complete repair and the deferred primary complete repair have been proposed.[13]
[14] In the standard-staged repair, a primary closure of the bladder without osteotomy, and without genital reconstruction in males, is attempted in the first 72 hours of life; between 6 and 12 months of age, the epispadias repair is performed in males. Bladder neck reconstruction follows around the age of 5 years, if a reasonable bladder capacity is reached.
Patients whose bladders fail to grow before bladder neck reconstruction (to at least 100 mL of capacity), or fail keep growing after bladder neck reconstruction thereby causing persistent incontinence or upper urinary tract deterioration, are candidate to undergo augmentation cystoplasty. A segment of sigmoid colon or ileum can be used to augment the bladder.[15]
Augmented bladders generally lose the ability to empty volitionally to completion; therefore, periodical clean intermittent catheterizations become necessary. As the reconstructed urethra is unreliable for catheterization, bladder augmentation is combined with placement of a catheterizable conduit bridging the bladder to the skin. The conduit can be created using the appendix (i.e., Mitrofanoff appendicovesicostomy) or a 2 to 3 cm long segment of ileum (i.e., Monti ileovesicostomy) and should be patent to a 12–14 Ch tube.[16] The most common complications include stomal stenosis and urinary leakage via the conduit.[17] The appendix is generally less keen than is the ileal tissue to develop complications.[18]
Long-Term Complications and Outcome
Modern-staged repair of the EEC as previously described has shifted the goal from patient's survival to quality of life. The single most important outcome in bladder exstrophy repair is probably urinary continence,[18] which is more easily achieved with successful primary bladder closure and good bladder growth.[19] The latter occurs as an adaptation of the bladder wall to the increase in bladder outlet resistances after bladder closure and after bladder neck reconstruction. Of note, this increase in resistances should never happen at the cost of upper urinary tract deterioration, which may occur in case of poorly compliant bladders with incomplete emptying.[20] Reportedly, up to 80% of cases can achieve a socially acceptable urinary continence (3-hour dry interval during daytime and volitional voiding) using this surgical strategy.[21] Nevertheless, many series report that 20 to 50% of cases will require bladder augmentation eventually.[15]
Genital function keeps being a relevant problem in patients with exstrophy long term. Males can experience problems for the presence of a short penis or persistent penile curvature.[22]
Excessive bladder-neck tapering may cause seminal obstruction and recurrent epididymitis leading to infertility. Female patients can experience problems because of the abnormal genital appearance, stenosis of the vaginal introitus, and pelvic organ prolapse.[23] These problems, however, do not generally impair a good quality of life.[24]
Although patients with exstrophy have almost invariably an abnormal gait in the long term because of the recurrence of the pelvic diastasis, which invariably recurs also in patients undergoing osteotomy, long-term orthopedic complications are rare.[25] Patients receiving an osteotomy may experience transient of persistent nerve damage, hip pain, and unequal length of limbs.[26]
Conclusion
Reportedly, modern-staged repair of EEC can achieve a socially acceptable urinary continence (3-hour dry interval during daytime and volitional voiding) in up to 80% of cases after successful primary closure[21]; sexual function can be an issue in the long term (particularly in males),[22]
[23] but overall quality of life can be good.[24]
