Bladder Exstrophy-epispadias Complex Research Articles

The impact of classic bladder exstrophy-epispadias repair in adult patients without continence

Background: Bladder exstrophy-epispadias complex is a rare congenital anomaly. Very few patients grow with the condition intact in their adulthood which lead to compromise in the results of repair. We herein report our experience of correction of the defects in the adult patients in single stage without doing osteotomy andurinary diversion. Methods: The sample size was 13 patients over ten years. All were treated in single stage. Bladder neck repair was done using paraurethral tissue, primary abdominal closure was done without flap, epispadias repair was done using modified Cantwell-Ransley procedure and hernial repair was done without mesh. No osteotomy was done. All the patients were followed regularly. Minimum period of follow-up was one year. Urinary continence, change in habits and subjective assessment of well-being were also noted.Results: 86.4% patients were totally incontinent. Bladder and anterior abdominal wall were closed in all the patients. Complete epispadias was possible in15.3% patients and rest were converted into coronal hypospadias. Hernia was repaired in 23% patients. All the patients were satisfied with their cosmetic results and they were able to interact socially. Conclusions: Surgical correction of the exstrophy-epispadias complex is possible in adulthood in the hands of experts in single stage without osteotomy. Regular cystoscopic examination and urine cytology yearly are recommended to diagnose the malignant changes in the native bladder as early as possible. Psychological, social and self-level of satisfaction is high among these patients after the surgical correction.

Impact of bilateral ureteral reimplantation at the time of complete primary repair of bladder exstrophy on reflux rates, renogram abnormalities and bladder capacity

Bilateral ureteral reimplantation at the time of the complete primary repair of bladder exstrophy (BUR-CPRE) has been proposed and has demonstrated favorable outcomes in the past. However, the potential benefits, including prevention of vesicoureteral reflux (VUR) and renal scarring must be tempered with any risks of reimplantation, persistent VUR, and the potential for overtreatment. We aimed to determine the impact of BUR-CPRE on reflux rates, renogram findings and bladder capacity. An IRB approved registry of children treated for bladder exstrophy epispadias complex (BEEC) during a long-term international collaboration hosted in a region with high prevalence of BEEC was queried. Children undergoing primary CPRE for bladder exstrophy (BE) were identified. Surgical procedure and outcome measures nuclear medicine dimercaptosuccinic acid (DMSA) scintigraphy scans, voiding cystourethrogram (VCUG), and urodynamic study (UDS) were assessed for presence and degree of VUR, renogram abnormalities, and bladder capacity. A total cohort of 147 patients with BEEC was queried; 52 children (37 males, 71%) underwent primary CPRE for BE between 2009 and 2019at median age of 1.1 years (IQR 0.6-1.9 years) with median follow up 4.4 years (IQR 2.4-6.4 years). BUR-CPRE was performed in 22/52 (42%). After BUR-CPRE, children were less likely to have VUR (any VUR present in 9 of 20 with imaging (45%) compared to 23 of 26 with imaging (82%) in the CPRE alone group (p=0.007)). VUR in the BUR-CPRE group tended to be unilateral and lower grade in comparison to the CPRE alone group. DMSA abnormalities were less common in the BUR-CPRE group (4/19 (21%) vs.12/27 (44%)), although the difference did not reach statistical significance (p=0.1). At 4 years follow-up, the BUR-CPRE group had a larger bladder capacity (p=0.016). After BUR-CPRE, children had a lower rate of VUR, and when present, VUR was more often unilateral and lower grade compared to the CPRE alone group. Fewer numbers of children in the BUR-CPRE group depicted DMSA abnormalities. No children developed obstruction after BUR-CPRE and none have undergone repeat reimplantation. We documented a larger bladder capacity at the time of maximum follow-up available (4 years)-but further data are needed to confirm this observation. BUR-CPRE decreases the incidence and severity of VUR after CPRE, but the clinical significance of this remains unclear. We are encouraged by these initial results, but since BUR-CPRE does not uniformly eliminate VUR, we continue to proceed carefully in the well selected patient.

Variant of Bladder Exstrophy With an Intact Penis: Surgical Options and Approach

Variants of bladder exstrophy are a rare but diverse spectrum of bladder exstrophy-epispadias complex. This case series describes a group of 4 unique exstrophy variant cases who had an intact phallus, but a completely open bladder plate. These patients underwent exstrophy repair and concomitant umbilicoplasty at the Civil Hospital, Ahmedabad as part of the US-India Multi-institutional Bladder Exstrophy Collaboration and were followed at the same institution. We believe that a detailed assessment of bladder neck prior to reconstructive repair and bladder closure would be beneficial in these cases as the extent of bladder neck involvement would affect reconstructive approach.

Substitution Phalloplasty in Patients With Bladder Exstrophy-Epispadias Complex: A Systematic Review of Techniques, Complications and Outcomes

BackgroundMales born with bladder exstrophy-epispadias complex generally have a shorter phallus, split corpora with dorsal curvature, and a scarred and flattened glans, so substitution phalloplasty is often required. AimThe aim of this study was to review the techniques, complications, and outcomes of substitution phalloplasty in bladder exstrophy-epispadias complex patients to determine the ideal surgical procedure and gauge the risks and benefits for the patient. MethodsA systematic review of the literature was performed using PubMed/MEDLINE and the Cochrane Library with the following terms: (“phalloplasty”); ((“epispadias”) OR (“bladder exstrophy”) OR (“cloacal exstrophy”)). We included only full-text articles reporting data about techniques and outcomes of substitution phalloplasty in patients with bladder exstrophy-epispadias complex. OutcomesTo determine whether patients with bladder exstrophy-epispadias complex might benefit from substitution phalloplasty. ResultsWe selected 7 studies involving 47 patients. All the studies were characterized by a low level of evidence and a heterogeneous approach during treatment and outcome assessment. The free radial forearm flap was the most commonly performed technique (89%) with an overall complication rate of 15%. Urethroplasty was performed in 22 of 47 (47%) patients, and in most cases (20/22) a “tube-within-the-tube” technique was performed simultaneously with the phalloplasty (20/47). Urethroplasty complications were recorded in 12 of 22 (54%) patients with 6 fistulae and 6 stenoses. A penile prosthesis was implanted in 32 of 47 (68%) patients and complications occurred in 8 of 32 (25%) patients with 6 erosion. Aesthetic, sexual, and psychological outcomes were satisfactory, but none of the studies used validated instruments for the final assessment. Clinical ImplicationsIt was not possible to formulate any recommendations based on a high level of evidence regarding substitution phalloplasty in patients with bladder exstrophy-epispadias complex. Strength & LimitationTo our knowledge, this is the first review to address bladder exstrophy-epispadias complex patients only. The limitations are mainly represented by the small number of cases because of the rarity of this disease and by the fact that no studies used validated instruments. ConclusionSubstitution phalloplasty in patients with bladder exstrophy-epispadias complex can achieve good functional, aesthetic, psychological, and sexual outcomes. It requires multiple procedures and carries a high complication rate. Multicentric studies including the assessment of patients by means of a validated questionnaire which investigates both sexual function and psychosexual satisfaction are required.Berrettini A, Sampogna G, Gnech M, et al. Substitution Phalloplasty in Patients With Bladder Exstrophy-Epispadias Complex: A Systematic Review of Techniques, Complications, and Outcomes. J Sex Med 2021;18:400–409.

New Insights on the Basic Science of Bladder Exstrophy-epispadias Complex

The exstrophy-epispadias complex is a rare congenital anomaly presenting as a wide spectrum of disorders. The complex nature of this malformation leads to continuous investigations of the basic science concepts behind it. Elucidating these concepts allows one to fully understand the mechanisms behind the disease in order to improve diagnosis, management, and treatment ultimately leading to improvement in patient quality of life. Multiple technological advancements within the last 10 years have been made allowing for new studies to be conducted. Herein, the authors conduct a literature review of studies from 2009 to 2019, considering novel theories regarding the genetics, embryology, bladder, bony pelvis, prostate, and genitalia of patients with bladder exstrophy-epispadias complex.

Fertility and sexuality issues in congenital lifelong urology patients: female aspects.

With advances in treatment modalities and medical knowledge, girls with congenital urologic disorders are living well into adulthood. Although, sexual and reproductive function in this population is still poorly understood. The aim is to review existing literature about fertility and sexuality in women with congenital genitourinary disorders, including spina bifida (SB), bladder exstrophy-epispadias complex (BEEC) and congenital adrenal hyperplasia (CAH). This review represents the joint SIU-ICUD (Société Internationale d'Urologie-International Consultation on Urological Disease) consultation on congenital lifelong urology. The results of this analysis were first presented at a joint consultation of the SIU and ICUD at the 2018 SIU annual conference in Seoul, South Korea. Appropriate experts were asked to write specific sections regarding sexuality and reproductive function in female patients with these complex congenital urogenital disorders. Each expert performed their own literature review which was reviewed by GDW, AFS, Hadley M. Wood and Dan Wood. Expert opinion was obtained where data are non-existent. Only about half of the individuals with SB express a satisfactory sex life. In women with BEEC, cosmetic concerns surrounding genital appearance and function may increase psychological distress, including severe depression, suicide and sexual dysfunction. Professional health care is key for improving self-esteem and to interact in the biopsychosocial model of the quality of life. Patients with SB and BEEC should be informed about all the potential risks and difficulties before, during and after pregnancy. Screening for pelvic organ prolapse is important as it can exacerbate their already existing sexual dysfunction, difficulties achieving pregnancy and challenges with clean intermittent catheterization. Lifelong multidisciplinary follow-up and management are complex but necessary. As these patients grow into their adolescence, they may have the desire to become involved in personal relationships and have sexual interactions. Their healthcare team needs to be increasingly sensitive to these aspects.

Single-staged male bladder exstrophy-epispadias complex reconstruction with pubic bone adaptation without osteotomy: 15-year single-center experience.

To represent the 15years' experience of an academic referral center for the reconstruction of bladder exstrophy-epispadias complex with a modified single-stage approach. Single-staged reconstruction techniques are commonly used for classic bladder exstrophy. However, combined bladder closure and epispadias repair have been taken into great consideration in patients with initially failed reconstruction or delayed primary closure. A total of 49 boys underwent 1-stage bladder and epispadias repair with pubic bone adaptation and without the application of pelvic osteotomy. The mean ± SD age at surgery was 5.23 ± 2.04months. Continence and social dryness were assessed in the follow-ups with 3months intervals for the first year and biannually thereafter. The mean ± SD of follow-up was 127.25 ± 71.32months. Urethrocutaneous fistula, stricture, wound infection, and hemiglans were developed in six distinct patients. However, no other major complications were noted. Three patients (6.1%) remained incontinent; while 32 (65.3%) children were socially continent and 14 (28.6%) children were waiting for toilet training. All the patients without previous failed closure were socially continent, while all incontinent patients had two failed closures in their history. No patient was rendered hypospadiac. Based on the experience of this institution, the application of single-stage reconstructive techniques can lead to continence, cosmetically pleasing appearance with promising outcomes, and reduction of overall operations, hospital stay and costs in the majority of cases as compared to multiple surgical procedures.

SLC20A1 Is Involved in Urinary Tract and Urorectal Development.

Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.

Variants in ALX4 and their association with genitourinary defects.

Genitourinary anomalies occur in approximately 1% of humans, but in most cases, the cause is unknown. Aristaless-like homeobox 4 (ALX4) is an important homeodomain transcription factor. ALX4 mutations in humans and mouse have been associated with craniofacial defects and genitourinary anomalies such as cryptorchidism and epispadias. To investigate the presence and the functional impact of ALX4 variants in patients with genitourinary defects. Two separate patient cohorts were analyzed. One includes clinical exome-sequencing (ES) data from 7500 individuals. The other includes 52 ALX4 Sanger-sequenced individuals with bladder exstrophy-epispadias complex (BEEC). Dual luciferase assays were conducted to investigate the functional transcriptional impact of ALX4 variants in HeLa cells and HEK293 cells. A total of 41 distinct ALX4 heterozygous missense variants were identified in the ES cohort with 15 variants present as recurrent in multiple patients. p.G369E and p.L373F were the only two present in individuals with genitourinary defects. A p.L373F heterozygous variant was also identified in one of the 52 individuals in the BEEC cohort. p.L373F and p.G369E were tested in vitro as both are considered damaging by MutationTaster, although only p.G369E was considered damaging by PolyPhen-2. p.L373F did not alter transcriptional activity in HeLa and HEK293 cells. p.G369E caused a significant 3.4- and 1.8-fold decrease in transcriptional activities relative to wild-type ALX4 in HEK293 and HeLa cells, respectively. Our study supports the idea that transcription factors like ALX4 could influence the normal development of the GU tract in humans as demonstrated in mouse models as ALX4 variant p.G369E (predicted pathogenic by multiple databases) affects ALX4 function in vitro. Variant p.L373F (predicted pathogenic by only MutationTaster) did not affect ALX4 function in vitro. Exon-sequence information and mouse genetics provide important insights into the complex mechanisms driving genitourinary defects allowing the association of transcriptional defects with congenital disorders.

Outcomes of inflatable penile prosthesis insertion using a neotunica allograft in neophalluses of patients on the bladder exstrophy–epispadias complex spectrum

Men born on the bladder exstrophy-epispadias complex (BEEC) spectrum may undergo neophallus reconstruction with a variety of free flaps, most commonly radial forearm. In order to achieve erectile function, a penile prosthesis may be inserted following neophallus construction. In this study, we sought to describe the perioperative and clinical outcomes of inflatable penile prosthesis (IPP) insertion into neophalluses of patients along the BEEC spectrum. Using a prospectively maintained institutional BEEC database, patients who had undergone both neophallus creation and IPP placement were identified for this study. Surgery was performed by two surgeons with expertise in IPP implantation. Operative details and postoperative outcomes and complications were collected with review of the medical record. Overall, there were a total of 13 men who underwent neophallus reconstruction with subsequent IPP placement. Of these men, 76.9% (10/13) had experienced successful primary closure in childhood. One patient had corporal loss secondary to complete primary repair of exstrophy (CPRE) following a failed primary attempt. The average age at IPP placement was 23.2 years (SD±5.06). Mean OR time (n=11) was 244.8min (SD±46.2). 76.9% (10/13) of the cases used AlloDerm™ as a neotunica albuginea for support of the IPP. Three patients (23.1%) experienced complications all of which required revision surgery. Two of these complications were erosions in patients for whom AlloDerm™ was not used in the initial IPP placement. The results of this study suggest that IPP placement in neophalluses of males on the BEEC spectrum have low perioperative and postoperative morbidity with successful outcomes. While the rate of complications is notably higher in this group compared to the native penis IPP literature, the use of AlloDerm™ or other allograft materials may help to narrow this gap. IPP placement in neophalluses of men on the BEEC spectrum is successful in the majority of cases. Complications may be reduced with the use of AlloDerm™ in initial placement.

Initial Experience of Pediatric Urology Consortium in Taking Care of Children with Bladder Exstrophy: the Search for the Holy Grail

The bladder exstrophy-epispadias complex is a very rare and complex spectrum of congenital anomalies. The holy grail of treatment for BEEC is volitional voiding with preservation of the upper tracts and patient satisfaction. The development of a collaboration can increase the exposure and experience for a panel of surgeons to better improve the care of babies with this anomaly, both in the surgical correction and in the pre- and post-operative care. The reported outcomes after exstrophy repair vary widely due to different approaches to closure as well as the variable outcome measures used to report experiences. While it is yet too soon to report on final continence outcomes, over the last 6 years, a collaboration between three institutions has increased by three-fold the experience for every individual under the guidance of an experienced coach. The treatment of patients with bladder exstrophy and epispadias is a complex anatomic and physiologic process that requires careful attention to a precise surgery while also focusing on the long-term growth of the bladder and keeping the upper tracts safe. This collaboration, which is predicated on a dedicated team with a focused target, has increased experience and exposure to exstrophy for all institutions.

Health-Related Quality of Life in Patients with the Bladder Exstrophy-Epispadias Complex and Relationship to Incontinence and Sexual Factors: A Review of the Recent Literature.

The bladder exstrophy-epispadia complex (BEEC) includes malformations with midline closing defects of the lower abdomen and external genitalia. Long-term consequences with urinary incontinence and sexual dysfunction, in spite of multiple surgical interventions, are common and expected to affect the patient's health-related quality of life (HRQOL). The extent and the predictive factors are, however, not known. New patient-reported outcome research is emerging, but valid and reliable condition-specific HRQOL are still missing. The aim of this review is to summarize and discuss the latest published reports (2015-2019) on HRQOL in patients with the BEEC and its relationship to incontinence and sexual factors.

Challenges in pediatric urologic practice: a lifelong view.

The role of the pediatric urologic surgeon does not end with initial reconstructive surgery. Many of the congenital anomalies encountered require multiple staged operations while others may not involve further surgery but require a life-long follow-up and often revisions. Management of most of these disordersmust extend into and through adolescence before transitioning these patients to adult colleagues. The primary goal of management of all congenital uropathies is protection and/or reversal of renal insult. For posterior urethral valves, in particular, avoidance of end-stage renal failure may not be possible in severe cases due to the congenital nephropathy but usually can be prolonged. Likewise, prevention or minimization of urinary tract infections is important for overall health and eventual renal function. Attainment of urinary continence is an important goal for most with a proven positive impact on quality of life; however, measures to achieve that goal can require significant efforts for those with neuropathic bladder dysfunction, obstructive uropathies, and bladder exstrophy. A particular challenge is maximizing future self-esteem, sexual function, and reproductive potential for those with genital anomalies such as hypospadias, the bladder exstrophy epispadias complex, prune belly syndrome, and Mullerian anomalies. Few endeavors are rewarding as working with children and their families throughout childhood and adolescence to help them attain these goals, and modern advances have enhanced our ability to get them to adulthood in better physical and mental health than ever before.

Bladder Herniation as an Auto-Augmentation Technique in Bladder Exstrophy: Initial Experience in Patients with Small Bladder Plate

ObjectiveTo present our long-term experience of bladder plate herniation technique in patients with bladder exstrophy epispadias complex (BEEC) and inadequate bladder plate. MethodsTen BEEC patients with inadequate bladder plates were referred. The bladder underlying fascia was opened and the exstrophic bladder was fixed above the peritoneal cavity to herniate the peritoneal contents beneath the bladder plate so that the abdominal pressure would be directly transferred to the posterior bladder wall; causing gradual bladder expansion and auto-augmentation. In 5 patients, the inguinal hernia was fixed to increase the pressure transferred to the exstrophic bladder. The bladder capacity was measured while the patient was crying and when the bladder was enlarged. Cystometry and voiding cystourethrogram were performed before the application of this technique and during the next 6 to 8 months, to determine the bladder capacity for further primary bladder closure. ResultsThe bladder was enlarged during straining/crying without any complications. The average bladder capacity was increased about 2.5 to 3 times after 8 months of follow-up so that it was suitable for undergoing primary closure. None of the children needed bladder augmentation following the single-stage total BEEC reconstruction. ConclusionThis technique seems to be safe, effective, and feasible in patients with small-sized bladder and may be performed before the primary closure to increase the success rate. This technique may be effective in increasing the bladder capacity for staged bladder closure and bladder neck reconstruction without further need for bladder augmentation.

Fertility and sexuality issues in congenital lifelong urology patients: male aspects.

To review existing literature about fertility and sexuality of boys born with complex congenital genitourinary anomalies. A Pubmed review was performed in December 2018 to identify the most relevant original manuscripts regarding male complex congenital conditions affecting the urogenital system in male patients including spina bifida (SB), bladder exstrophy-epispadias complex (BEEC) and hypospadias. A comprehensive review was drafted exploring sexual dysfunction from a medical, psychosexual, surgical and reproductive point of view during transition from childhood (or adolescence) to adulthood. About 75% of men with SB have erectile dysfunction (ED) (Gamé et al. in Urology 67(3):566-570, 2006; Diamond et al. in 58(4):434-435, 1986). Most SB patients have impaired sexual development mainly due to diminished self-esteem, dependence on caregivers and lack of privacy (Blum et al. in Pediatrics 88(2):280-285, 1991). Men with BEEC have fewer intimate relationships than women because of the greater difficulties with issues regarding their genitalia and sexual activities (Deans et al. in Am J Obstet Gynecol 206(6):496.e1-496.e6, 2012). However, a good quality of life is achievable with the effective use of coping strategies (Deng et al. in Transl Androl Urol 7:941, 2018; Rikken et al. in BMC Womens Health 18(1):163, 2018; Friedler et al. in Reprod Biomed Online 32(1):54-61, 2016). Chordee occurs in 25% of all hypospadias patients. More severe hypospadias is related to a greater risk for complications. The long-term sexual quality of life (QoL) in men who underwent hypospadias surgery is influenced by a lot of factors. Therefore, an interactive and dynamic biopsychosocial model of sexual QoL was proposed. The care of patients with congenital urologic conditions becomes a challenge especially in the period of 'transition'. The goal of follow-up is a holistic management viewed from a medical, psychosexual, surgical end reproductive point. All patients should be asked for specific urinary, fecal or sexual concerns.

Let’s talk about sex: A review of expectations, body image and sexual function in exstrophy

Background: The bladder exstrophy epispadias complex (BEEC) is a rare disorder characterised by a number of genito-urinary abnormalities. The condition and subsequent treatment may result in lasting effects on continence, renal function and fertility. There are equally important psychosocial and psychosexual effects as part of overall long-term quality of life. The literature consists largely of small studies with variable methodology; this study aims to consolidate these data. Methods: This study reviews the available literature sourced from the Medline database using the keywords listed below. Results: Patients appear to be high achievers with good overall health-related quality of life. Most form close personal friendships although express anxiety related to revelation of their condition. Data suggest the majority of patients are able to engage in and be satisfied with sexual intercourse. Fertility may be adversely affected, but this can usually be overcome with assisted reproductive techniques and specialist input during pregnancy and delivery. Conclusions: Psychosocial and psychosexual outcomes in patients with BEEC may be excellent. Therefore careful transition and psychological support combined with long-term follow-up is important to allow these patients to maximise their quality of life. Level of evidence: Not applicable.

Current Indications and Techniques for the Use of Bowel Segments in Pediatric Urinary Tract Reconstruction.

Today, there are few indications for the use of bowel in pediatric urology. This is in large extent due to the successful conservative therapy in patients with neurogenic bladder and the improved success of primary reconstruction in patients with the bladder exstrophy-epispadias complex. Only after the failure of the maximum of conservative therapy or after failure of primary reconstruction, bladder augmentation, or urinary diversion should be considered. Malignant tumors of the lower urinary tract (e.g., rhabdomyosarcomas of the bladder/prostate) are other rare indications for urinary diversion. Replacement or reconstruction of the ureter with a bowel segment is also a quite rarely performed procedure. In this review, the advantages and disadvantages of the different options for the use of bowel segments for bladder augmentation, bladder substitution, urinary diversion, or ureter replacement during childhood and adolescence are discussed.

Classic bladder exstrophy and adenocarcinoma of the bladder: Methylome analysis provide no evidence for underlying disease-mechanisms of this association

The bladder exstrophy-epispadias complex (BEEC) represents the severe end of uro-rectal malformation spectrum involving aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). Long-term complications in CBE are malignancies of the bladder with 95% of them being adenocarcinomas. Since CBE and adenocarcinoma of the bladder are rare entities, their frequent co-occurrence suggests a common etiology. Recent studies suggest that promoter methylation of various genes play a crucial role during the phenotypical morphogenesis of adenocarcinomas of urinary bladder. To examine, whether epigenetic processes such as DNA methylation patterns are potentially associated with CBE, we performed Illumina 450 K methylation arrays in blood (n = 10) and tissue samples (n = 2) of CBE patients and healthy matched controls (n = 12). In our analysis, we found total lack of methylation in the blood and methylation differences were restricted to 10 CpG sites in the tissue samples. In comparison to other bladder anomalies, CBE tissue methylation profiles differ from those of adenocarcinoma, adenocarcinoma with CBE, urothelial carcinoma and urachal carcinoma. In this preliminary study, we did not provide any strong evidence of major DNA methylation alterations which would be suggestive for strong underlying epigenetic mechanism. However, larger studies are required to provide more robust statistical evidence to exclude smaller effects in the tissues.

Isolated bladder exstrophy in prenatal diagnosis.

Isolated classic bladder exstrophy (CBE) is the most common variant of the bladder-exstrophy-epispadias complex (BEEC). The BEEC represents a spectrum ranging from isolated epispadias over CBE to the most severe form, cloacal exstrophy. We report on a series of 12 cases with CBE diagnosed prenatally and illustrate the spectrum of prenatal ultrasound findings with comparison to prior published reports on this entity. This was a retrospective study involving 12 fetuses with CBE at two large tertiary referral centers in Germany over a 14-year period (2004-2018). Median diagnosis was made with ultrasound in 24 + 5 (IQR25,75: 21 + 2, 29 + 0) weeks of gestation. All fetuses presented with the pathognomonic findings non-visualization of the fetal bladder and protruding abdominal mass below the umbilical cord insertion. All fetuses showed normal kidney anatomy and normal amniotic fluid throughout pregnancy. Epispadia was visible prenatally on ultrasound in 6/8 male fetuses. 1/12 Parents opted for termination of pregnancy, 11/12 fetuses were live born and received reconstructive surgery. Isolated CBE is an extremely rare prenatal sonographic finding. Prenatal diagnostics should exclude additional malformations within the spectrum of cloacal malformations.

Complete penile disassembly in epispadias repair.

To report current results of complete penile disassembly technique in epispadias repair. In ten years, we have preformed 31 complete penile disassembly for proximal epispadias repair. Twenty-four patients had epispadias after primary repair of bladder exstrophy and 7 isolated penopubic epispadias. The age of the patients ranged from 10months to 6years (median 3years). The shortening of urethral plate was found in 30 patients (97% of cases), and this shortening varied between 6 and 16mm. However, in one patient we found a lengthening of the urethral plate of 8mm. The narrowing of urethral plate was found in all patients, and this narrowing varied between 30 and 50% of the width of the plate. Postoperative complications encountered in our patients were dominated by fistulas and dehiscence, particularly in patients who had bladder exstrophy-epispadias complex. After dehiscence and fistulas repair, the cosmetic results were satisfying in 25 patients (80.5% of cases) with conical glans and meatus in orthotopic position without any necrosis of the glans. However, the urinary continence ≥ 1h was observed in 6 patients (19% of cases) and only 3 patients (9.7% of cases) had a urinary continence ≥ 3h. The mean follow-up was 61 months. The complete penile disassembly remains one of the best techniques for epispadias repair. However, we noticed a reappearance of the dorsal curvature of the penis in a large number of patients treated for isolated epispadias and the impact of this technique on urinary incontinence remains uncertain.