Continuing Education Activity

Bladder exstrophy is a rare congenital anomaly characterized by a spectrum of anomalies involving the ventral body wall, urinary tract, genitalia, bony pelvis, spine, anus, etc. Its diagnosis is clinical and does not require any additional investigations. Precise surgery to provide acceptable continence rates remains the greatest challenge for pediatric surgeons. This activity outlines the etiology, pathogenesis, approaches for surgical management, and highlights the role of the interprofessional team in the care of patients with this condition.

Objectives:

• Outline various theories for the etiology of bladder exstrophy.
• Describe the evaluation of patients with exstrophy.
• Summarize the common approaches of surgical management of bladder exstrophy.

Introduction

Bladder exstrophy, one of the most serious congenital malformations, is characterized by a spectrum of anomalies involving the ventral body wall, urinary tract, genitalia, bony pelvis, spine, anus, etc.[1] The first description of exstrophy bladder dates back to 2000 BC.[2] 

After more than 100 years of the initial surgical management by Trendelenberg, bladder exstrophy continues to be the most difficult challenge for a pediatric surgeon. The prevalence of classical bladder exstrophy is approximately 3.3 per 1,00,000 live births, and it has gender predominance in males.[3] Multiple theories have been put forward for its etiopathogenesis; however, the exact cause still eludes us. The diagnosis of bladder exstrophy is clinical and does not require any ancillary investigations.

Two reconstructive approaches, the modern staged repair of exstrophy (MSRE) and the complete primary repair of exstrophy (CPRE), are commonly adopted by surgeons across the world. The aims of the surgical treatment are to provide a competent receptacle (bladder) for storage, to prevent upper tract damage, and to provide cosmetically acceptable genitalia providing good functional outcomes in terms of continence and sexual function.

Etiology

Although multiple theories highlighting the etiology and pathogenesis of bladder exstrophy have been published, the exact cause still eludes us. Of all these theories, the one by Marshall and Muecke is the most accepted. An abnormally large cloacal membrane causes a wedge effect and prevents the medial migration of the mesenchymal tissue. As a result, the lower abdominal wall is not well-formed. A subsequent rupture of the cloacal membrane results in herniation of all the contents and leading to the clinical picture of bladder-exstrophy-epispadias complex.[4] 

It has been suggested that 'the wedge-effect' can also occur due to abnormally cephalad origin of the primordia of the genital tubercle. Some experimental models suggest premature rupture of the cloacal membrane to be a significant contributing factor.[5]

Several other theories, including the caudal displacement of the genital tubercle, abnormal fluid retention leading to rupture of the embryonic bladder, etc., have been proposed as possible mechanisms in the occurrence of exstrophy bladder.[4] Recently, a new hypothesis has been suggested by Varma et al.[6] They have proposed that pubic diastasis is central to the occurrence of exstrophy bladder, and it precedes exstrophy development.

Epidemiology

Bladder exstrophy is a rare birth defect. As per the largest International dataset, its prevalence is approximately 2 per 100,000 births.[7] The estimated prevalence of classical bladder exstrophy in the United States is approximately 3.3 per 1,00,000 live births.[3] The disease is twice more common in boys as compared to girls. However, some studies have also shown a very high male preponderance, with M to F=6 to 1.[8] 

It is less prevalent among the non-white race, high or low socioeconomic status, and Western geographic region.[9] Additionally, studies have documented an increase in the risk of severe forms of the spectrum of Bladder-exstrophy-epispadias-complex (BEEC) with maternal smoking and irradiation during the first trimester. On the contrary, periconceptional folate decreases the risk of these sever forms.[10]

Pathophysiology

Bladder-exstrophy-epispadias-complex (BEEC) depicts a spectrum of birth defects, ranging from epispadias to cloacal exstrophy at the milder and the most severe ends of the spectrum. The classical bladder exstrophy is characterized by abnormalities involving the lower urinary tract, abdominal wall, bony pelvis, genitalia, pelvic floor, spine, and the anus.[8] 

As a general rule, all the structures, including the bladder, urethra, vagina, and rectum, are displaced anteriorly in bladder exstrophy. The distorted anatomy of the bony pelvis in bladder exstrophy needs a special mention. The 'open book configuration' of the pelvis is an appropriate term for its description. The main abnormalities in the bony pelvis include pubic diastasis, shorter anterior segments, and outward rotation of the anterior and posterior segments.

In children with exstrophy, the pubic diastasis is around 4 cm at birth and increases to around 8 cm by the age of 10 years. Contrary to this, in a normal human, the distance is less than 1 cm at all ages. It has been postulated that a disruption in the symphyseal ligaments might be responsible for this. Secondly, the anterior segments of the bony pelvis are approximately 30% shorter. However, the dimensions of the posterior segments of the bony pelvis are within normal limits. Both, the anterior and posterior segments of the bony pelvis, are also externally rotated.[11]

History and Physical

The diagnosis of bladder exstrophy is clinical and is made by the pediatrician as soon as the baby is born in the majority of cases. A fleshy, red mass prolapsing out of the suprapubic region represents the open bladder plate. There is continuous urine leakage from the mass. As a rule, the degree of bladder plate exposure correlates with the degree of pubic diastasis. Therefore, the bladder prolapse can range from only exposed trigone to the entire bladder. The ureteric orifices are often visible, but an attempt of blind poking or cannulating the orifices must not be made. In male newborns, the phallus is short, stubby, and has a dorsal chordee (pointing upwards). The glans is flattened with widely separated (divergent) corpora due to the wide pubic diastasis.

The testis may not be descended at birth, and occasionally there may be the presence of bilateral inguinal hernias. In females, the clitoris is bifid with a slightly anterior vaginal opening. Uterine and vaginal duplications are also not uncommon in these children. Apart from these, both male and female newborns have an anterior ectopic anus due to abnormalities of the pelvic floor. A patulous anal orifice with mucosal prolapse can be seen in some children with exstrophy bladder. Although the management of bladder exstrophy begins from the time of birth only, it is not uncommon for some children to present later in life.

This happens especially in developing countries. In this subset of patients, a severe excoriation in the para-exstrophy skin, hypertrophied-polypoidal bladder plate with squamous metaplasia, poor control over bowel movements, and waddling gait are common. Social problems due to the continuous wetting of clothes are also frequently seen in these children. 

Evaluation

The diagnosis of exstrophy bladder is clinical and does not require any other additional investigations. Routine hemogram and blood chemistry are performed as a part of the preoperative work-up. Obtaining plain radiographs of the abdomen and pelvis to know the degree od pubic diastasis is crucial. Due to continuous urine leakage, it is uncommon to have upper tract damage before bladder plate closure. However, an ultrasound KUB to rule out associated anomalies of the upper urinary tract should be done.

Other radiological investigations and nuclear scintigraphy scans are reserved for follow-up purposes only. In females, it is always better to rule out the associated anomalies of the Mullerian structures by an ultrasound abdomen or perineal ultrasound. Evaluating the local microflora by taking a 'bladder swab' before surgery is performed by some surgeons; however, evidence supporting this practice is lacking.

Treatment / Management

Preoperative Care of the Exposed Bladder

Covering of the bladder plate with a non-adherent wrap or film not only avoids trauma and bleeding by the diaper but also prevents the formation of polyps. A polypoidal bladder is always difficult to close. Various films, wraps, and dressings have been used for the protection of the bladder plate. A clear plastic wrap or a saran wrap is the most commonly used.[12]

Surgical Treatment: surgical treatment of classical bladder exstrophy not only involves the bladder closure, but it also includes procedures such as epispadias repair, bladder neck reconstruction, bladder augmentation, and ureteric reimplantation. Additionally, the abnormalities in the bony pelvis and the pelvic floor need to be addressed along with exstrophy repair. Various procedures have been described for bladder exstrophy. They fall into two main categories: the reconstructive procedures and the diversion procedures. The modern approaches focus mainly on the reconstructive procedure; however, the Mainz group in Germany has favored the diversion procedures and has highlighted different aspects from time to time. The major goals of exstrophy repair include the closure of the bladder and creating a receptacle for storage that grows with the child, preservation of the upper tract function, and reconstruction of the genitalia providing good functional outcomes in terms of continence and sexual function.[13] 

We will discuss some aspects of the common procedures of exstrophy repair, as a thorough discussion, including all the technical points is beyond the scope of this article. Among the reconstructive procedures, the two procedures that are commonly performed by pediatric surgeons across the globe are modern staged repair of exstrophy (MSRE) and complete primary repair of exstrophy (CPRE). Other procedures, which are less popular, include Kelly's radical soft tissue mobilization, Warsaw procedure, etc.

(I) modern staged repair of exstrophy (MSRE): the procedure was developed and refined by Jeffs and Gearhart. The main principle is to perform a staged repair (in three separate procedures) at appropriate times. The ideology is each procedure will provide some degree of outlet resistance and will help the bladder to grow. The first step is the primary turn-in, which is performed in the first three days, might avoid osteotomy, protect the lower abdominal skin from ammoniacal contents, and prevent the bladder from trauma. Although the first stage is performed in the newborn age, occasionally it has to delay. This is done where the bladder template is very small, and the closure is technically not feasible. The second stage, epispadias repair or genitalia reconstruction, is performed at 6 to 9 months of age. This ensures early bladder cycling and provides outlet resistance for the bladder to grow. Bladder neck reconstruction is the third procedure and is performed at a time when the child has sufficient bladder capacity (at least 100 ml) and has attained a certain age. It is usually done at 4 to 5 years of age when the child is in the school-going age and can participate in voiding training.[14] The sequence of the mentioned procedures is not universal, as some surgeons perform bladder neck reconstruction before epispadias repair.[15]

(II) Complete primary repair of exstrophy (CPRE): also is known as Mitchell's repair as it was first performed by Michael Mitchell. The procedure aims at performing the complete repair, including bladder turn-in, bladder neck repair, and epispadias repair in a single sitting. The ideology is the initiation of early bladder cycling to ensure the optimal development of the bladder. The subsequent surgeries are also avoided. The procedure utilizes complete penile disassembly and division of the intersymphyseal bands, such that the vesicourethral unit is buried deep into the pelvis.[16]

Osteotomy: due to abnormalities of the bony pelvis, there is tension on the bladder and the abdominal wall following turn-in. The issue can be solved by performing an osteotomy. However, this is not universally performed the procedure and depends on the surgeon's preference along with the child's age. Different types of osteotomies have been performed by different surgeons including anterior osteotomy of the pubic ramus, anterior innominate osteotomy (with or without vertical posterior osteotomy), posterior iliac osteotomy, etc. Among these, the anterior innominate osteotomy offers various advantages including less blood loss, easy external fixation, and no need to turn the patient to perform the osteotomy, etc. [11][17][15]

Other Procedures: It has been highlighted in various studies that the extrophied bladders fail to grow, even when primary turn-in is performed at an early age. Therefore, a good proportion of patients require augmentation of the bladder with other conduits. The most commonly performed procedures include ileocystoplasty, colocystoplasty, and gastrocystoplasty. Although each has its own merits and demerits, gastrocystoplasty offers some additional advantages of few metabolic complications, physiological superiority in children with deranged renal function, and less risk of calculi formation.[17]

Differential Diagnosis

Classical bladder exstrophy has to be differentiated from other anomalies of the spectrum of bladder-exstrophy-epispadias-complex. It includes epispadias, at the mild end of the spectrum, characterized by the involvement of the only genitalia. The bladder is uninvolved in epispadias. Another anomaly, which lies at the most severe end of the spectrum, is cloacal exstrophy. It is also known as OEIS complex due to the presence of omphalocele, exstrophy of bladder, imperforate anus, and spinal abnormalities. The differentiation of bladder exstrophy from both these anomalies is based on clinical examination and doesn't require any other ancillary investigation. The other group of rare anomalies that must be differentiated from bladder exstrophy is the 'exstrophy variants.' These are also referred to as 'split symphysis variants.' These differ from the classical bladder exstrophy in the fact that they lack bladder abnormalities. Although the bladder is closed, there is a presence of pubic diastasis and divergent recti. The following are included in the category of exstrophy variants:

Pseudoexstrophy: the covering over the bladder consists only of the skin. The musculoskeletal abnormalities, including divergent recti and pubic diastasis, are noticeable. When the bladder is distended, it bulges out like a hernia.[18]

Superior Vesical Fissure: the bladder is normally formed; however, there is an opening from the skin into the bladder leading the bladder to prolapse. It must be differentiated from patent urachus as there is an absence of musculoskeletal abnormalities in a patent urachus.

Duplicate exstrophy: there is the presence of a normal bladder with a normal phallus. In adjacent to the normal bladder, there is a suprapubic exstrophic mucosal plate. The exstrophic bladder plate is dry and does not receive any ureters. The presence of a superior vesical fissure that later gets fused is supposed to be responsible for this anomaly.[18]

Covered exstrophy: it is different from pseudoexstrophy in the fact that there is the presence of an isolated ectopic bowel segment. This is present on the inferior abdominal wall. Another important difference from other variants is the presence of abnormalities of the external genitalia in covered exstrophy.[18]

Prognosis

Continence: functional voiding outcomes must be assessed in terms of the dry period and continence. But, there is no universally accepted definition of urinary continence. According to the Johns Hopkins group, continence was defined as the dry period of at least 3 hours during the day, dry during the night, able to void without clean intermittent catheterization (CIC), and no need for augmentation. They have shown that 70% of their patients had continence as per this definition.[13] In comparison to this, the Indiana group shows overall urinary continence of more than 80% in their patients. But approximately 70% of their patients also underwent augmentation.[19] The continence rates described by the Seattle group are comparable to the Johns Hopkins group. After CPRE, over 70% of the patients achieved daytime continence of more than 2 hours.

Upper tract damage: hydronephrosis or upper tract dilatation is commonly seen after the repair of exstrophy. After CPRE, it was seen in 53% of the patients during follow-up. Overall, 30% had bilateral hydronephrosis. Male gender is associated with worse renal outcomes.[20] Recurrent urinary tract infection (UTI) and renal scarring occur in approximately 11.5% and 5.7% of the patients, respectively, after MSRE.[21] Mouriquand et al. report UTI and persistent upper tract dilatation in 65% and 26% of their patients after MSRE. [22]

Sexual function: the majority of the patients have a normal long-term sexual function. Fertility, which is normal in females, is significantly low in males. Patients who have undergone diversion procedures have better ejaculatory function and fertility as compared to those who have undergone reconstructive procedures.[23]

Complications

The most common complications of the surgical treatment of bladder exstrophy are wound dehiscence and bladder dehiscence. Complete dehiscence can cause bladder prolapse. It can be prevented by adequate mobilization of the flaps and by incorporating osteotomy during bladder turn-in, thus reducing the tension over the abdominal wall and bladder plate.

Other complications: painful micturition or dysuria: this is very common after open bladder surgeries and is due to bladder spasms, wound infection, urethral obstruction: this complication has reduced over time as the use of paraexstrophy flaps has declined. When urethral obstruction or stricture occurs, the first step is to perform urethral dilatation. Urethrocutenous fistula, urethral stricture, loss of hemiglans/corpora, and persistent dorsal chordee: These complications usually occur after epispadias repair. Persistent incontinence, urinary tract infection (UTI), and bladder stones: These complications occur after bladder neck reconstruction. Osteotomy complications: risk of malignancy: There is a 1-2% risk of development of malignancy of the bladder. Adenocarcinoma is the most common type of malignancy seen in patients of bladder exstrophy. It has been shown that this can develop in even the unrepaired bladders.

Postoperative and Rehabilitation Care

Postoperative management of the child with bladder exstrophy is extremely crucial. Firstly, it includes postoperative analgesia and parenteral medications. The immediate pain is managed by the epidural analgesia. Intravenous analgesia may be required for a longer duration as the child may suffer pain from the traction and immobilization. Enteral feeds can be started as soon as the child is fully awake. Care must be taken to maintain the immobilization of the lower extremities. Secondly, whether an osteotomy is performed or not, immobilization of the lower extremities is generally preferred by most of the pediatric surgeons. For osteotomy, a 4-week period of external fixation is generally recommended.[17]

Thirdly, the postoperative introduction of anticholinergic medications to maintain the relaxed state of the detrusor and to avoid detrusor spasms might help. Finally, care must be taken to maintain the indwelling drains and catheter to ensure optimal outcomes. Following discharge, it is important to ensure a regular follow-up. Follow-up investigations to ensure upper tract preservation, including Ultrasound KUB, micturating cystourethrography (MCUG), and renal scintigraphy studies, must be performed. Lower tract function should be assessed by the urodynamic study.

Consultations

Patients of exstrophy usually require long-term follow-up; therefore, the involvement of multiple disciplines is necessary for their optimal care. Neonatologist and pediatrician plays a vital role in the pre-operative management of these children. Surgical consultation has to be sought immediately after birth, as an early repair generally obviates the need for osteotomy. For osteotomy, consultation with a trained pediatric surgeon is required. Long-term upper tract functional assessment requires consultation with a nephrologist. When these patients enter adolescence and adulthood, there are certain psychosocial and sexual issues that need to be addressed properly. Therefore, consultation with a psychiatrist and a urologist/andrologist is required during their transitional care.

Deterrence and Patient Education

The most important factor in the quality of life of patients with exstrophy bladder is the degree of urinary continence. Those who attain a sufficient bladder size with age can hold urine for 2 to 3 hours during the day and remain dry during the night as well. However, a considerable proportion of children may not be able to do so due to poor bladder growth. This may lead to psychosocial issues, school dropouts, delays in the education of these children, etc. Also, parental issues, including work leaves, have also been highlighted in the literature. Engaging the child in a voiding program, educating about the benefits of clean intermittent catheterization (CIC), training him/her regarding the procedure of self-CIC, ensuring proper hygiene, ensuring compliance of the medications, etc. are crucial steps that must be reinforced to the parents periodically.

Enhancing Healthcare Team Outcomes

While a pediatric surgeon is always involved in the care of patients with exstrophy bladder, it is crucial to consult with an interdisciplinary team of specialists. The neonatologist or pediatrician, who is involved in the immediate management of the baby after birth, has an important role in the care of the exposed bladder plate and the surrounding skin. Covering of the bladder plate with a saran wrap/plastic wrap not only avoids trauma and bleeding but also aids in surgical closure of the bladder template by preventing the formation of polyps. Consultation with a nephrologist is crucial, as there will be a deterioration in the upper tract function after the bladder closure. Therefore, engaging the nephrologist right from the beginning is always beneficial.

The nurses are also a vital member of the interprofessional group. They play a major role in educating the parents and the patients about clean intermittent catheterization (CIC) and ensure their compliance. The pharmacist might ensure that the patient is on correct formulation and doses of anticholinergic medications. A urologist and a psychiatrist play a crucial role in the management of the psychosexual issues at the time of transitional care. Thus, the demand for precise planning and discussion with the interprofessional team involved in the management of the patient is highly recommended to lower the morbidity and to improve outcomes.[24]