RARE DISEASE
Exstrophy-epispadias complex
Exstrophy-epispadias complex
Exstrophy-epispadias complex
Synonyms: BEEC, Bladder exstrophy-epispadias-cloacal extrophy complex, EEC
Synonyms: BEEC, Bladder exstrophy-epispadias-cloacal extrophy complex, EEC
Synonyms: BEEC, Bladder exstrophy-epispadias-cloacal extrophy complex, EEC
Drug discovery
1
drug
With orphan designation
Overview
The Exstrophy-epispadias complex (EEC) encompasses a spectrum of congenital genitourinary malformations ranging from epispadias to severe cloacal exstrophy. These midline defects involve exposed bladder tissues, pelvic diastasis, and musculoskeletal anomalies, often accompanied by gastrointestinal, spinal, or renal abnormalities [1][5][16]. Surgical reconstruction aims to achieve urinary continence, preserve renal function, and improve quality of life through staged or single-stage repairs [3][18].
Population
Burden
Requires median 5-7 surgeries by adulthood, with 17-32% complication rates (e.g., dehiscence, obstruction) [14][18]
60-70% achieve continence with surgery; persistent incontinence correlates with depression/anxiety [4][16]
Lifetime costs exceed $2M/patient due to multidisciplinary care needs and lost productivity [9]
Therapies
Surgical repair: Staged closure (bladder/pelvis → epispadias repair → bladder neck reconstruction) or single-stage complete primary repair (CPRE) [3][13][18]
Adjunctive measures: Pelvic osteotomies, testosterone pre-treatment for penile growth, and post-operative immobilization [14][18]
Secondary interventions: Bladder augmentation (30-40% of cases), continent urinary diversions, and management of complications (e.g., fistulas, reflux) [4][14]
Categories: rare abdominal surgical diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare renal diseases, rare transplant-related disorders, rare urogenital diseases
Research Papers
578 drug discovery papers about Exstrophy-epispadias complex, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
578 drug discovery papers about Exstrophy-epispadias complex, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2023-01-07 | Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies
Replacement of detrusor smooth muscle (SM) with connective tissue (CT) in the bladder wall has functional consequences to lower urinary tract function, namely changes to the filling compliance and its contractile performance. In children with congenital anomalies such tissue remodelling may underlie the poor prognosis that is characteristic of a significant proportion of these patients. We have quantified the extent of CT deposition in bladder tissue samples from four age-matched (24–72 months) patient groups, namely: normally-functioning (control) bladders; bladder exstrophy, neurogenic bladders (NGB) and posterior urethral valves (PUV). In addition, using multiplex labelling we have also quantified, in neighbouring sections, expression of TGF-β, a downstream transcription factor SMAD2, connexin-43, as well as DAPI labelling of nuclear material, separately in the SM and CT regions of the detrusor layer. TGF-β receptor (TGF-βR) and Cx43 labelling were greater in SM regions of exstrophy and NGB (but not PUV) tissues when compared to control, were but unchanged in CT regions. SMAD2 labelling was similar in all groups in both SM and CT regions, with minor increases in exstrophy, NGB and PUV SM regions and small reductions in exstrophy and NGB CT regions. DAPI staining was less in CT compared with SM regions but was unchanged between patient groups. Overall, the TGF-β pathway shows variability of expression in congenital bladder anomalies, compared with control tissue, that at this period of post-natal development is greater in the extant SM layer. Antifibrotic strategies that target this pathway offer an approach to minimise fibrotic development.
2022-05-30 | Progesterone regulates inflammation and receptivity of cells via the NF-κB and LIF/STAT3 pathways.
A high concentration of blood ammonia can lead to failure of early embryo implantation in dairy cows. Progesterone (P4) is an important hormone that regulates the changes of uterine receptivity and participates in pregnancy during early implantation. However, whether P4 alleviates the harmful effects of blood ammonia is unknown. Therefore, this experiment treated bovine endometrial epithelial cells (BEEC) with ammonia chloride and P4. The results showed that ammonia decreased the viability of BEEC, upregulated the ROS level and apoptosis rate, and upregulated the expressions of Bax, Bcl-2, P53, Cyt-c, caspase-3, caspase-8 and caspase-9. It also upregulated the expressions of TLR4, NF-κB, and in turn, produced a large amount of IL-6 and downregulated the expressions of EGF and VEGF. After co-treating BEEC with ammonia and P4, P4 had no alleviating effect on cell viability, ROS and apoptosis, but downregulated the expressions of TLR4, NF-κB, IL-6, and upregulated the expressions of LIF, EGF and VEGF. Inhibition of STAT3 signaling pathway, LIF expression was not affected, and VEGF expression was down-regulated. Using LIF treated BEEC, VEGF expression was upregulated, but after the addition of inhibitors, the expression of VEGF was not upregulated by LIF. Therefore, progesterone could not alleviate the oxidative stress and apoptosis induced by ammonia in BEEC. However, progesterone ameliorated the inflammation and receptivity genes of BEEC induced by ammonia via the NF-κB and LIF/STAT3 signaling pathways.
2019-04-01 | Functional, histological and molecular characteristics of human exstrophy detrusor
Bladder exstrophy is a congenital anomaly involving foetal exposure and protrusion of the open bladder through an incomplete lower abdominal wall. Techniques to surgically correct exstrophy after birth have greatly improved, but it still presents a major challenge to achieve continence and a good quality of life for patients and their families as the pathophysiology of bladder dysfunction is unknown.A multimodal approach was used to characterise the histological and biomechanical properties of exstrophy detrusor. These were correlated with myocyte responses to agonists and an evaluation of developmental signalling pathways to evaluate the cause of bladder dysfunction in exstrophy.Detrusor muscle specimens were obtained during corrective surgery from four exstrophy groups: neonatal (1-3 days, n = 8), younger children (7 months-5 years, n = 13) and older children (8-14 years, n = 11) undergoing secondary procedures and cloacal exstrophy (16 days-9 years, n = 9); control specimens were obtained from children (3 months-9 years, n = 14) undergoing surgery for other pathologies but with normal bladder function. Five lines of experiments were undertaken: measurement of connective tissue to detrusor muscle ratio, contractile responses to electrical and agonist stimulation; in vitro biomechanical stiffness, intracellular Ca2+ responses to contractile agonists and immunohistochemistry for proteins (MMP-7, cyclinD1, β-catenin and c-myc) involved in fibrosis generation. Exstrophy data were compared with those from the control group.Exstrophy tissue demonstrated reduced smooth muscle compared with connective tissue, reduced contractile responses and greater mechanical stiffness. However, intracellular Ca2+ responses to agonists were maintained. These changes were greatest in neonatal and cloacal exstrophy samples and least in those from older paediatric bladders. Immunolabelled MMP-7, β-catenin and c-myc were reduced in exstrophy samples.These results highlight the reality that newborns with exstrophy have significantly reduced compliance and bladder underactivity, which may persist or return to normal values with surgery and age. The primary cause of underactivity is increased connective tissue in relation to detrusor muscle; however, detrusor myocyte function remains normal. Finally, the increase of the smooth muscle content in the paediatric bladder group indicates a remodelling response of the bladder to surgical correction and time. Excess gestational fibrosis is associated with changed expression of key proteins in the Wnt-signalling pathway, a potential aetiological factor and therapeutic target.Results point to connective tissue deposition as the primary pathological process that determines bladder function with normal myocyte function. Future research that reduces connective tissue deposition may lead to improvement in outcomes for these children.
2017-08-03 | Lessons learned from the management of adults who have undergone augmentation for spina bifida and bladder exstrophy: Incidence and management of the non‐lethal complications of bladder augmentation
The present review provides clinical insights and makes recommendations regarding patient management garnered by the long-term follow up of patients undergoing enteric bladder augmentation for the management of congenital anomalies. A prospectively maintained database on 385 patients that have experienced an enteric bladder augmentation, using either the ileum or colon, was reviewed. Evaluations included methods used to prevent bladder calculi formation and recurrence, the incidence and etiology of renal calculi development, the incidence and treatment of vitamin B12 deficiency, and the complications and need for surgical revisions for continent catheterizable stomas. A significantly increased risk for continent catheterizable stomal complications occurred after Monti-Yang tube formation, 70% (21/30 patients), compared with appendicovesicostomy, 41% (27/66 patients), P = 0.008. Both procedures had significantly more complications than continent catheterizable stomas using tapered ileum with a reinforced ileal-cecal valve, 21% (13/63 patients), P < 0.0001 and P < 0.013, respectively. Approximately 50% of the patient population developed a body mass index ≥30 during adulthood. The onset of obesity resulted in significantly more complications developing in patients with a Monti-Yang tube (87%; 13/15 patients) or appendicovesicostomy (55%; 18/33 patients) compared with a tapered ileum with a reinforced ileal-cecal valve (27%, 8/30 patients), P < 0.00015 and P < 0.025, respectively, with a median follow-up interval of 16 years, range 10-25 years. Long-term follow-up evaluations on patients undergoing an enteric bladder augmentation are necessary to prevent the long-term sequela of this procedure. The key to improving patient prognosis is the nutritional management of the patient as they mature, especially if a continent abdominal stoma is going to be carried out.
2017-08-02 | Comparing the bulking effect of calcium hydroxyapatite and Deflux injection into the bladder neck for improvement of urinary incontinence in bladder exstrophy-epispadias complex.
The aim of this study was to evaluate the efficacy of the endoscopic injection of calcium hydroxyapatite (CaHA) into the bladder neck (BN) region of patients with urinary incontinence and bladder exstrophy-epispadias complex (BEEC). We designed a retrospective cohort study in which we retrospectively studied medical charts of female and male patients of BEEC who had undergone CaHA or Deflux injection for continence improvement between 2009 and 2014. Sixteen incontinent patients with a mean ± SD age of 8.09 ± 3.5 years received an endoscopic submucosal injection of 5.4 ml of pure CaHA powder with autologous plasma (group A). Patients in group B (N = 21), control group, with a mean ± SD age of 7.51 ± 2.8 years received Deflux injection (5.1 ml). The mean follow-up after injection was 38 ± 5.2 and 33 ± 4.1 months in groups A and B, respectively. No post-injection complication was detected in none of the patients during the follow-up. Eleven patients (68.75%) in group A became socially dry following 1-2 injections, the degree of incontinence was improved in 4 patients (25%), and there was no change in one patient (6.25%). However, Deflux injection resulted in complete dryness in 14 (66.66%), improvement in the degree of incontinence in 5 (23.81%) and no change in 2 patients (9.52%), leading to no significant difference in continence achievement between CaHA and Deflux groups (p = 0.9). The statistical analysis was not significantly different in terms of bladder capacity (p = 0.7) or Q max (p = 0.8). The preliminary results of this study revealed that CaHA may be applied as an affordable bulking agent in treatment of urinary incontinence in BEEC.
proteins
2025-06-14 | Medium- and long-term results of botulinum toxin injection in patients with bladder augmentation: A retrospective study and literature review.
To determine the medium and long-term results and safety of botulinum toxin treatment in enlarged patients with incontinence secondary to overactive bladder and compared it with literature review. a prospective study was performed analysing the results of 41 procedures performed between 2010 and 2023 in a total of 14 patients with a history of bladder augmentation and clinical or urodynamic findings suggestive of overactive bladder or low compliance. A total of 41 procedures were performed on 14 patients. 71 % of patients received previous oral treatment, the average between the bladder augmentation and the first injection was 20 years. The re-injection rate was 71 % with a mean time between procedures of 19 months. 61 % of the patients presents clinical response. No differences were found in terms of underlying pathology, epidemiological factors, urodynamic parameters or combined vs single bladder patch injections. Differences were found regarding previous use of anticholinergic treatment. Botulinum toxin treatment is safe and effective for patients with cystoplasty and may avoid a major procedure in those patients than show symptomatology or urodynamic findings with overactive bladder or a low accommodation.
2025-03-31 | Platelet secretions exert anti-inflammatory effects in vitro on neutrophils and uterine epithelia in cattle: a possible role in amplifying the uterine immune network toward pregnancy
Our findings reveal for the first time that platelet secretions directly act on PMNs and BEECs in vitro, thereby assisting the uterine immune network to shift anti-inflammatory environment toward pregnancy. The present study can explain, in part, the successful applications of platelet derivatives in reproductive medicine.
2024-12-12 | Isolated Bladder Exstrophy: A Rare Case
Exstrophy-Epispadias Complex (EEC) is a rare congenital malformation of the lower genitourinary tract, with a worldwide incidence of 1 per 46,000 live births. This case report presents a rare occurrence of bladder exstrophy variant in a one-day-old male newborn. The patient presented with Isolated bladder exstrophy and normal phallus with imperforated anus, congenital heart disease, and a left ectopic kidney. During palpation, protruding intestinal contents were identified, exerting pressure posteriorly on the exstrophied bladder. Surgical interventions included cut-back anoplasty, bilateral ureteral reimplantation, and primary bladder closure in a single operation, resulting in a successful outcome without complications. Three months of follow-up showed satisfactory surgical results. However, future continence levels should be monitored, and corrective surgery performed if necessary. Further research and case studies are warranted to enhance our understanding of this rare condition and optimize management strategies for affected individuals.
2024-10-01 | Trio Exome Sequencing Implicates Wnt Signaling in the Pathogenesis of Bladder-Exstrophy-Epispadias Complex
Background: Bladder-exstrophy-epispadias complex (BEEC) describes a spectrum of lower abdominal and genitourinary midline malformations, including epispadias, bladder exstrophy, and cloacal exstrophy. Although the cause of BEEC is uncertain, increased concordance rates among monozygotic (62%) vs. dizygotic twins (11%) and previously identified BEEC candidate genes suggest a hereditary component. This study aims to uncover novel genetic causes of BEEC through exome analysis. Methods: We performed exome sequencing for 38 BEEC case-parent trios and 57 singlet probands who received care at a single institution between 09/2022 and 04/2024. For analysis, we employed a candidate gene approach utilizing a list of 130 genes curated from previously published BEEC genomic studies and mouse models. Unbiased exome analysis was also conducted to identify novel BEEC candidate genes. Results: We identified a de novo pathogenic variant in PORCN (c.1186C>T; p.Arg396*) in one proband with bladder exstrophy and focal dermal hypoplasia (FDH). PORCN is required for Wnt protein secretion, and variants have previously been described in patients with both bladder exstrophy and FDH. In addition, we detected 2 potentially deleterious heterozygous variants in Wnt pathway genes among 2 singlet probands: WNT5A (c.1033G>C; p.Asp345His) and WNT8B (c.185G>A; p.Arg62His). Both variants have deleterious in silico prediction scores and show a strong conservation. Interestingly, WNT5A knockout mice display severe defects in urethral tube formation. Through unbiased trio analysis, we also identified 2 novel candidate genes in 2 probands: TAF5L (c.1328C>T, p.Thr443Met) and EVX1 (c.832C>A, p.Pro278Thr). Both variants arose de novo, have deleterious in silico prediction scores, are strongly conserved, and are absent from large population databases. EVX1 is a transcription factor involved in cloacal membrane development and acts downstream of WNT3A. Conclusion: Through exome analysis, we identified a pathogenic PORCN variant in one proband with bladder exstrophy and FDH, along with 3 potentially deleterious variants in Wnt pathway genes among 3 probands with BEEC. This further supports a role of Wnt signaling in disease pathogenesis. Funding: NIDDK Support
2018-04-25 | The Role of Human Acellular Dermis in Preventing Fistulas After Bladder Neck Transection in the Exstrophy-epispadias Complex
To evaluate human acellular dermis (HAD) as an adjunct during bladder neck transection (BNT) by comparing surgical outcomes with other types of tissue interposition.A prospectively maintained institutional database of exstrophy-epispadias complex (EEC) patients was reviewed for those who underwent a BNT with at least 6 months follow-up. The primary outcome was the occurrence of BNT-related fistulas.In total, 147 EEC patients underwent a BNT with a mean follow-up time of 6.9 years (range 0.52-23.35 years). There were 124 (84.4%) classic exstrophy patients, 22 (15.0%) cloacal exstrophy patients, and 1 (0.7%) penopubic epispadias patient. A total of 12 (8.2%) BNTs resulted in fistulization, including 4 vesicoperineal fistulas, 7 vesicourethral fistulas, and 1 vesicovaginal fistula. There were 5 (22.7%) fistulas in the cloacal exstrophy cohort and 7 (5.6%) fistulas in the classic bladder exstrophy cohort (P = .019). Using either HAD or native tissue flaps resulted in a lower fistulization rate than using no interposed layers (5.8% vs 20.8%; P = .039). Of those with HAD, the use of a fibrin sealant did not decrease fistulization rates when compared to HAD alone (6.5% vs 8.8%, P = .695). There was no statistical difference in surgical complications between the use of HAD and native flaps (8.6% vs 5%, P = .716).Use of soft tissue flaps and HAD is associated with decreased fistulization rates after BNT. HAD is a simple option and an effective adjunct that does not require harvesting of tissues in patients where a native flap is not feasible.
cell therapies
2026-08-04 | Use of platelet-rich fibrin in bladder exstrophy repair: A prospective study.
Penopubic fistula formation remains one of the most frequent early complications following bladder exstrophy repair. Platelet-rich fibrin (PRF), an autologous, high-concentration platelet, white blood cells, and fibrin biomaterial that enhances tissue healing and regeneration, has shown potential for surgical applications. However, PRF has not been applied in primary bladder exstrophy repair. This study aimed to assess the effectiveness of autologous PRF membrane applications in primary bladder exstrophy repair in male patients. This prospective randomized comparative study enrolled 20 male children with primary classical bladder exstrophy-epispadias complex who were surgically repaired at our center between 2022 and 2025. Patients were divided into two groups according to PRF usage: PRF group, with PRF use (n = 12, 60%); non-PRF group (controls), without PRF use (n = 8, 40%); allocation concealment was reached using sequentially numbered, opaque, sealed envelopes opened during the surgery. In the PRF group, 5-10 mL of the patient's autologous venous blood was obtained intraoperatively and centrifuged at 3000 revolutions per minute for 10 min to produce a PRF clot, which was then transformed into a dense fibrin membrane. The fibrin was stitched with PDS 6/0 onto the bladder neck angle dorsally before the approximation of the pubic symphysis. All the steps of the procedure were conducted according to the sterility requirements. The patients from both groups underwent osteotomy anteriorly with fixation of a metal construction externally. The mean operative time and length of hospital stay were comparable between the two groups. In the non-PRF group, 3 (37.5%) patients and 1 (12.5%) patient had penopubic fistula and wound dehiscence, respectively. Compared to the control group, the PRF group patients were complication-free, demonstrating a favorable preliminary signal (p = 0.014). PRF is a simple, feasible adjunct for covering the bladder neck junction, as it suggests a potential signal toward reducing penopubic fistula formation. Due to the small sample size, these results are hypothesis-generating, and adequately larger randomized comparative studies are needed to confirm these exploratory findings.
2026-01-12 | Multidisciplinary perioperative management of cloacal exstrophy bladder closure: A single institution's approach.
Cloacal Exstrophy (CE), also known as OEIS complex (Omphalocele, Exstrophy of the cloaca, Imperforate anus, and Spinal defects), is the rarest and most severe congenital malformation of the bladder exstrophy-epispadias spectrum, characterized by an open bladder and exposed portions of the large intestine, along with bony anomalies. The objective of this study is to describe the experience of a high-volume exstrophy center's perioperative pathway, with a focus on analgesic use as well as urologic, orthopedic, and dietary interventions, for bladder repair of cloacal exstrophy. An IRB-approved, prospectively-maintained institutional approved Bladder Exstrophy-Epispadias Complex database was reviewed for patients with CE who had undergone bladder closure between 2017 and 2024. Electronic medical records were retrospectively reviewed to examine patient demographics, use of pelvic osteotomy, immobilization status, pediatric intensive care unit (PICU) admission, perioperative analgesia and sedation, nutritional support, drainage tubes, blood transfusion, antibiotic coverage, hospital length of stay, postoperative complications and closure failure. One hundred seventy-six CE and CE-variant patients were identified and 23 underwent bladder closure during this period. The median age at pelvic osteotomy was 1.93 years (IQR, 1.48-2.43, range 1-7). A delay of 14 days (IQR, 10-16) between osteotomy and closure was used in all but two patients. External fixation device and Buck's traction remained for 42 (IQR, 42-47) days. Post-closure, PICU stay was 8 days (IQR, 7-13) with 78 % requiring invasive ventilation for 4.5 days (IQR, 2-13.8). All patients required blood transfusions (2, IQR, 1-3). Enteral feeding resumed by day 11.5 (IQR, 5.8-16.5) for all but one and parenteral nutrition for 21 days (IQR, 13.5-53). Patient-controlled analgesia (PCA) was used in all patients for both pre- and post-closure, morphine most commonly (76 % and 48 %, respectively). Opioid use totaled 45 days (IQR, 40-60). Acetaminophen use was universal and NSAIDs used in 43 % (pre) and 57 % (post), clonidine in 62 % (pre) and 96 % (post). Bladder closure was successful in 87 %, while 13 % required repeat operation. Length of stay averaged 62 days (IQR, 51-86), range 42-191. While our study was limited by a small patient population, this data highlights the complexity and resource-intensive nature of CE bladder closure, emphasizing the need for comprehensive multidisciplinary management at specialized centers. Our 87 % success rate in bladder closure for patients with CE underscores the effectiveness of the multidisciplinary approach described when managing the complex perioperative course of these patients. However, challenges remain including prolonged hospitalization, ventilation requirements and slow reintroduction of enteral nutrition while highlighting the optimization of perioperative strategies of pain, sedation and recovery.
2025-09-28 | Anesthetic management with ultrasound-guided caudal epidural catheter for primary closure of vesical exstrophy in a neonate: Case report
ABSTRACT: The exstrophy-epispadias complex is a spectrum of congenital malformations in which the main predictor for functional adverse outcomes and higher health costs is failed primary closure. We present the case of a 13-day old new-born who underwent primary closure of bladder exstrophy under general anaesthesia. We highlight some factors of the perioperative anaesthetic approach that may have influenced the successful primary closure. These factors include fluid management guided by hemodynamic goals and multimodal analgesic management involving an ultrasound-guided caudal epidural catheter.
2025-03-25 | Covered exstrophy of the bladder, approaches to treatment.
Introduction. Classic bladder exstrophy is a rare anomaly, occurring in a ratio of 1:30000 to 1:50000 newborns. However, various variants of the exstrophy-epispadias complex are 10 times less common. Covered bladder exstrophy is a rare variant of classic exstrophy. Patients with the covered variant of exstrophy can be considered as classic exstrophy with all the accompanying defects of this anomaly, but with a bladder that is closed and covered only by a thin, often translucent skin membrane without muscles or a fascial layer. Cases in this category of patients may be underestimated in terms of the size of the defect at initial detection. Case report. The article describes two rare clinical observations of treatment of children with covered bladder exstrophy. A 5-year-old boy underwent a full range of surgical treatment: primary closure of the bladder, Cohen ureterocystoneoimplantation, bladder neck plastic surgery, bilateral iliac osteotomy, with reduction and fixation of the pubic bones. A 10-year-old girl underwent plastic surgery of the anterior abdominal wall, bilateral iliac osteotomy, and reduction (convergence) of the pubic bones. Conclusions. It is important to follow the principles of classical exstrophy correction in the treatment of children with covered bladder exstrophy. In the presence of symptoms of urinary incontinence, bladder neck reconstruction is indicated, this will improve continence and promote adequate bladder growth. Correct treatment of these malformations of the genitourinary system can significantly improve the quality of life of these patients.
2021-07-15 | Urothelial Differences in the Exstrophy-Epispadias Complex: Potential Implications for Management.
The authors examined the urothelium of exstrophy-epispadias complex spectrum patients for histological differences and expression of terminal markers of urothelial differentiation. Between 2012 and 2017 bladder biopsies were obtained from 69 pediatric exstrophy-epispadias complex patients. These specimens were compared to bladder specimens from normal controls. All bladder specimens underwent histological assessment followed by immunohistochemical staining for uroplakin-II and p63. Expression levels of uroplakin-II and p63 were then assessed by a blinded pathologist. Forty-three classic bladder exstrophy biopsies were obtained (10 newborn closures, 22 delayed closures, and 11 repeat closures). Additional biopsies from 18 cloacal exstrophy patients and 8 epispadias patients were also evaluated. These specimens were compared to 8 normal control bladder specimens. Overall, uroplakin-II expression was lower in exstrophy-epispadias complex patients compared to controls (p <0.0001). Among classic bladder exstrophy patients, there was reduced expression of uroplakin-II in the delayed and repeat closures in comparison to newborn closures (p=0.045). Expression of p63 was lower in patients with exstrophy-epispadias complex compared to controls (p <0.0001). Expression of p63 was similar among classic bladder exstrophy patients closed as newborns when compared to delayed or repeat closures. Classic bladder exstrophy patients had a higher rate of squamous metaplasia when compared to controls (p=0.044). Additionally, there was a higher rate of squamous metaplasia in the patients undergoing delayed closure in comparison to those closed in the newborn period (p <0.001). The urothelium in the exstrophy-epispadias complex bladder is strikingly different than that of healthy controls. Uroplakin-II expression is greatly reduced in exstrophy-epispadias complex bladders and is influenced by the timing of bladder closure. Reduced uroplakin-II expression and increased rates of squamous metaplasia in exstrophy-epispadias complex patients undergoing delayed closure suggests that exposure of the urothelium may induce these changes. These findings shed light on the molecular changes in exstrophy-epispadias complex bladders and may have implications on the appropriate timing of primary bladder closure, as those closed in the newborn period appear to have a greater potential for growth and differentiation.
antibodies
2023-12-08 | Urothelial carcinoma occurring in a defunctionalized bladder after urinary diversion due to the bladder exstrophy‐epispadias complex
Introduction The bladder exstrophy‐epispadias complex is a rare congenital disease. Urothelial carcinomas rarely occur in patients with this disease, and there have been few reports on its treatment. Case presentation We report the case of a 44‐year‐old man with a hemorrhage from the external urethral meatus. He was diagnosed with bladder exstrophy‐epispadias complex and underwent urinary diversion with substitution cystoplasty and Mitrofanoff appendicovesicostomy. Because computed tomography and magnetic resonance imaging suggested invasive bladder carcinoma in the defunctionalized bladder, we performed a cystectomy. The patient was diagnosed with urothelial carcinoma with glandular differentiation. One month after the surgery, nivolumab adjuvant chemotherapy was administered. The patient showed no signs of recurrence or metastasis after the treatment. Conclusion This is the first case of adjuvant nivolumab therapy for urothelial carcinoma with the bladder exstrophy‐epispadias complex.
small molecules
2023-01-07 | Quantification of the TGF- β/SMAD fibrosis pathway in bladder wall samples from children with congenital lower urinary tract anomalies
Replacement of detrusor smooth muscle (SM) with connective tissue (CT) in the bladder wall has functional consequences to lower urinary tract function, namely changes to the filling compliance and its contractile performance. In children with congenital anomalies such tissue remodelling may underlie the poor prognosis that is characteristic of a significant proportion of these patients. We have quantified the extent of CT deposition in bladder tissue samples from four age-matched (24–72 months) patient groups, namely: normally-functioning (control) bladders; bladder exstrophy, neurogenic bladders (NGB) and posterior urethral valves (PUV). In addition, using multiplex labelling we have also quantified, in neighbouring sections, expression of TGF-β, a downstream transcription factor SMAD2, connexin-43, as well as DAPI labelling of nuclear material, separately in the SM and CT regions of the detrusor layer. TGF-β receptor (TGF-βR) and Cx43 labelling were greater in SM regions of exstrophy and NGB (but not PUV) tissues when compared to control, were but unchanged in CT regions. SMAD2 labelling was similar in all groups in both SM and CT regions, with minor increases in exstrophy, NGB and PUV SM regions and small reductions in exstrophy and NGB CT regions. DAPI staining was less in CT compared with SM regions but was unchanged between patient groups. Overall, the TGF-β pathway shows variability of expression in congenital bladder anomalies, compared with control tissue, that at this period of post-natal development is greater in the extant SM layer. Antifibrotic strategies that target this pathway offer an approach to minimise fibrotic development.
2022-05-30 | Progesterone regulates inflammation and receptivity of cells via the NF-κB and LIF/STAT3 pathways.
A high concentration of blood ammonia can lead to failure of early embryo implantation in dairy cows. Progesterone (P4) is an important hormone that regulates the changes of uterine receptivity and participates in pregnancy during early implantation. However, whether P4 alleviates the harmful effects of blood ammonia is unknown. Therefore, this experiment treated bovine endometrial epithelial cells (BEEC) with ammonia chloride and P4. The results showed that ammonia decreased the viability of BEEC, upregulated the ROS level and apoptosis rate, and upregulated the expressions of Bax, Bcl-2, P53, Cyt-c, caspase-3, caspase-8 and caspase-9. It also upregulated the expressions of TLR4, NF-κB, and in turn, produced a large amount of IL-6 and downregulated the expressions of EGF and VEGF. After co-treating BEEC with ammonia and P4, P4 had no alleviating effect on cell viability, ROS and apoptosis, but downregulated the expressions of TLR4, NF-κB, IL-6, and upregulated the expressions of LIF, EGF and VEGF. Inhibition of STAT3 signaling pathway, LIF expression was not affected, and VEGF expression was down-regulated. Using LIF treated BEEC, VEGF expression was upregulated, but after the addition of inhibitors, the expression of VEGF was not upregulated by LIF. Therefore, progesterone could not alleviate the oxidative stress and apoptosis induced by ammonia in BEEC. However, progesterone ameliorated the inflammation and receptivity genes of BEEC induced by ammonia via the NF-κB and LIF/STAT3 signaling pathways.
2019-04-01 | Functional, histological and molecular characteristics of human exstrophy detrusor
Bladder exstrophy is a congenital anomaly involving foetal exposure and protrusion of the open bladder through an incomplete lower abdominal wall. Techniques to surgically correct exstrophy after birth have greatly improved, but it still presents a major challenge to achieve continence and a good quality of life for patients and their families as the pathophysiology of bladder dysfunction is unknown.A multimodal approach was used to characterise the histological and biomechanical properties of exstrophy detrusor. These were correlated with myocyte responses to agonists and an evaluation of developmental signalling pathways to evaluate the cause of bladder dysfunction in exstrophy.Detrusor muscle specimens were obtained during corrective surgery from four exstrophy groups: neonatal (1-3 days, n = 8), younger children (7 months-5 years, n = 13) and older children (8-14 years, n = 11) undergoing secondary procedures and cloacal exstrophy (16 days-9 years, n = 9); control specimens were obtained from children (3 months-9 years, n = 14) undergoing surgery for other pathologies but with normal bladder function. Five lines of experiments were undertaken: measurement of connective tissue to detrusor muscle ratio, contractile responses to electrical and agonist stimulation; in vitro biomechanical stiffness, intracellular Ca2+ responses to contractile agonists and immunohistochemistry for proteins (MMP-7, cyclinD1, β-catenin and c-myc) involved in fibrosis generation. Exstrophy data were compared with those from the control group.Exstrophy tissue demonstrated reduced smooth muscle compared with connective tissue, reduced contractile responses and greater mechanical stiffness. However, intracellular Ca2+ responses to agonists were maintained. These changes were greatest in neonatal and cloacal exstrophy samples and least in those from older paediatric bladders. Immunolabelled MMP-7, β-catenin and c-myc were reduced in exstrophy samples.These results highlight the reality that newborns with exstrophy have significantly reduced compliance and bladder underactivity, which may persist or return to normal values with surgery and age. The primary cause of underactivity is increased connective tissue in relation to detrusor muscle; however, detrusor myocyte function remains normal. Finally, the increase of the smooth muscle content in the paediatric bladder group indicates a remodelling response of the bladder to surgical correction and time. Excess gestational fibrosis is associated with changed expression of key proteins in the Wnt-signalling pathway, a potential aetiological factor and therapeutic target.Results point to connective tissue deposition as the primary pathological process that determines bladder function with normal myocyte function. Future research that reduces connective tissue deposition may lead to improvement in outcomes for these children.
2017-08-03 | Lessons learned from the management of adults who have undergone augmentation for spina bifida and bladder exstrophy: Incidence and management of the non‐lethal complications of bladder augmentation
The present review provides clinical insights and makes recommendations regarding patient management garnered by the long-term follow up of patients undergoing enteric bladder augmentation for the management of congenital anomalies. A prospectively maintained database on 385 patients that have experienced an enteric bladder augmentation, using either the ileum or colon, was reviewed. Evaluations included methods used to prevent bladder calculi formation and recurrence, the incidence and etiology of renal calculi development, the incidence and treatment of vitamin B12 deficiency, and the complications and need for surgical revisions for continent catheterizable stomas. A significantly increased risk for continent catheterizable stomal complications occurred after Monti-Yang tube formation, 70% (21/30 patients), compared with appendicovesicostomy, 41% (27/66 patients), P = 0.008. Both procedures had significantly more complications than continent catheterizable stomas using tapered ileum with a reinforced ileal-cecal valve, 21% (13/63 patients), P < 0.0001 and P < 0.013, respectively. Approximately 50% of the patient population developed a body mass index ≥30 during adulthood. The onset of obesity resulted in significantly more complications developing in patients with a Monti-Yang tube (87%; 13/15 patients) or appendicovesicostomy (55%; 18/33 patients) compared with a tapered ileum with a reinforced ileal-cecal valve (27%, 8/30 patients), P < 0.00015 and P < 0.025, respectively, with a median follow-up interval of 16 years, range 10-25 years. Long-term follow-up evaluations on patients undergoing an enteric bladder augmentation are necessary to prevent the long-term sequela of this procedure. The key to improving patient prognosis is the nutritional management of the patient as they mature, especially if a continent abdominal stoma is going to be carried out.
2017-08-02 | Comparing the bulking effect of calcium hydroxyapatite and Deflux injection into the bladder neck for improvement of urinary incontinence in bladder exstrophy-epispadias complex.
The aim of this study was to evaluate the efficacy of the endoscopic injection of calcium hydroxyapatite (CaHA) into the bladder neck (BN) region of patients with urinary incontinence and bladder exstrophy-epispadias complex (BEEC). We designed a retrospective cohort study in which we retrospectively studied medical charts of female and male patients of BEEC who had undergone CaHA or Deflux injection for continence improvement between 2009 and 2014. Sixteen incontinent patients with a mean ± SD age of 8.09 ± 3.5 years received an endoscopic submucosal injection of 5.4 ml of pure CaHA powder with autologous plasma (group A). Patients in group B (N = 21), control group, with a mean ± SD age of 7.51 ± 2.8 years received Deflux injection (5.1 ml). The mean follow-up after injection was 38 ± 5.2 and 33 ± 4.1 months in groups A and B, respectively. No post-injection complication was detected in none of the patients during the follow-up. Eleven patients (68.75%) in group A became socially dry following 1-2 injections, the degree of incontinence was improved in 4 patients (25%), and there was no change in one patient (6.25%). However, Deflux injection resulted in complete dryness in 14 (66.66%), improvement in the degree of incontinence in 5 (23.81%) and no change in 2 patients (9.52%), leading to no significant difference in continence achievement between CaHA and Deflux groups (p = 0.9). The statistical analysis was not significantly different in terms of bladder capacity (p = 0.7) or Q max (p = 0.8). The preliminary results of this study revealed that CaHA may be applied as an affordable bulking agent in treatment of urinary incontinence in BEEC.
proteins
2025-06-14 | Medium- and long-term results of botulinum toxin injection in patients with bladder augmentation: A retrospective study and literature review.
To determine the medium and long-term results and safety of botulinum toxin treatment in enlarged patients with incontinence secondary to overactive bladder and compared it with literature review. a prospective study was performed analysing the results of 41 procedures performed between 2010 and 2023 in a total of 14 patients with a history of bladder augmentation and clinical or urodynamic findings suggestive of overactive bladder or low compliance. A total of 41 procedures were performed on 14 patients. 71 % of patients received previous oral treatment, the average between the bladder augmentation and the first injection was 20 years. The re-injection rate was 71 % with a mean time between procedures of 19 months. 61 % of the patients presents clinical response. No differences were found in terms of underlying pathology, epidemiological factors, urodynamic parameters or combined vs single bladder patch injections. Differences were found regarding previous use of anticholinergic treatment. Botulinum toxin treatment is safe and effective for patients with cystoplasty and may avoid a major procedure in those patients than show symptomatology or urodynamic findings with overactive bladder or a low accommodation.
2025-03-31 | Platelet secretions exert anti-inflammatory effects in vitro on neutrophils and uterine epithelia in cattle: a possible role in amplifying the uterine immune network toward pregnancy
Our findings reveal for the first time that platelet secretions directly act on PMNs and BEECs in vitro, thereby assisting the uterine immune network to shift anti-inflammatory environment toward pregnancy. The present study can explain, in part, the successful applications of platelet derivatives in reproductive medicine.
2024-12-12 | Isolated Bladder Exstrophy: A Rare Case
Exstrophy-Epispadias Complex (EEC) is a rare congenital malformation of the lower genitourinary tract, with a worldwide incidence of 1 per 46,000 live births. This case report presents a rare occurrence of bladder exstrophy variant in a one-day-old male newborn. The patient presented with Isolated bladder exstrophy and normal phallus with imperforated anus, congenital heart disease, and a left ectopic kidney. During palpation, protruding intestinal contents were identified, exerting pressure posteriorly on the exstrophied bladder. Surgical interventions included cut-back anoplasty, bilateral ureteral reimplantation, and primary bladder closure in a single operation, resulting in a successful outcome without complications. Three months of follow-up showed satisfactory surgical results. However, future continence levels should be monitored, and corrective surgery performed if necessary. Further research and case studies are warranted to enhance our understanding of this rare condition and optimize management strategies for affected individuals.
2024-10-01 | Trio Exome Sequencing Implicates Wnt Signaling in the Pathogenesis of Bladder-Exstrophy-Epispadias Complex
Background: Bladder-exstrophy-epispadias complex (BEEC) describes a spectrum of lower abdominal and genitourinary midline malformations, including epispadias, bladder exstrophy, and cloacal exstrophy. Although the cause of BEEC is uncertain, increased concordance rates among monozygotic (62%) vs. dizygotic twins (11%) and previously identified BEEC candidate genes suggest a hereditary component. This study aims to uncover novel genetic causes of BEEC through exome analysis. Methods: We performed exome sequencing for 38 BEEC case-parent trios and 57 singlet probands who received care at a single institution between 09/2022 and 04/2024. For analysis, we employed a candidate gene approach utilizing a list of 130 genes curated from previously published BEEC genomic studies and mouse models. Unbiased exome analysis was also conducted to identify novel BEEC candidate genes. Results: We identified a de novo pathogenic variant in PORCN (c.1186C>T; p.Arg396*) in one proband with bladder exstrophy and focal dermal hypoplasia (FDH). PORCN is required for Wnt protein secretion, and variants have previously been described in patients with both bladder exstrophy and FDH. In addition, we detected 2 potentially deleterious heterozygous variants in Wnt pathway genes among 2 singlet probands: WNT5A (c.1033G>C; p.Asp345His) and WNT8B (c.185G>A; p.Arg62His). Both variants have deleterious in silico prediction scores and show a strong conservation. Interestingly, WNT5A knockout mice display severe defects in urethral tube formation. Through unbiased trio analysis, we also identified 2 novel candidate genes in 2 probands: TAF5L (c.1328C>T, p.Thr443Met) and EVX1 (c.832C>A, p.Pro278Thr). Both variants arose de novo, have deleterious in silico prediction scores, are strongly conserved, and are absent from large population databases. EVX1 is a transcription factor involved in cloacal membrane development and acts downstream of WNT3A. Conclusion: Through exome analysis, we identified a pathogenic PORCN variant in one proband with bladder exstrophy and FDH, along with 3 potentially deleterious variants in Wnt pathway genes among 3 probands with BEEC. This further supports a role of Wnt signaling in disease pathogenesis. Funding: NIDDK Support
2018-04-25 | The Role of Human Acellular Dermis in Preventing Fistulas After Bladder Neck Transection in the Exstrophy-epispadias Complex
To evaluate human acellular dermis (HAD) as an adjunct during bladder neck transection (BNT) by comparing surgical outcomes with other types of tissue interposition.A prospectively maintained institutional database of exstrophy-epispadias complex (EEC) patients was reviewed for those who underwent a BNT with at least 6 months follow-up. The primary outcome was the occurrence of BNT-related fistulas.In total, 147 EEC patients underwent a BNT with a mean follow-up time of 6.9 years (range 0.52-23.35 years). There were 124 (84.4%) classic exstrophy patients, 22 (15.0%) cloacal exstrophy patients, and 1 (0.7%) penopubic epispadias patient. A total of 12 (8.2%) BNTs resulted in fistulization, including 4 vesicoperineal fistulas, 7 vesicourethral fistulas, and 1 vesicovaginal fistula. There were 5 (22.7%) fistulas in the cloacal exstrophy cohort and 7 (5.6%) fistulas in the classic bladder exstrophy cohort (P = .019). Using either HAD or native tissue flaps resulted in a lower fistulization rate than using no interposed layers (5.8% vs 20.8%; P = .039). Of those with HAD, the use of a fibrin sealant did not decrease fistulization rates when compared to HAD alone (6.5% vs 8.8%, P = .695). There was no statistical difference in surgical complications between the use of HAD and native flaps (8.6% vs 5%, P = .716).Use of soft tissue flaps and HAD is associated with decreased fistulization rates after BNT. HAD is a simple option and an effective adjunct that does not require harvesting of tissues in patients where a native flap is not feasible.
cell therapies
2026-08-04 | Use of platelet-rich fibrin in bladder exstrophy repair: A prospective study.
Penopubic fistula formation remains one of the most frequent early complications following bladder exstrophy repair. Platelet-rich fibrin (PRF), an autologous, high-concentration platelet, white blood cells, and fibrin biomaterial that enhances tissue healing and regeneration, has shown potential for surgical applications. However, PRF has not been applied in primary bladder exstrophy repair. This study aimed to assess the effectiveness of autologous PRF membrane applications in primary bladder exstrophy repair in male patients. This prospective randomized comparative study enrolled 20 male children with primary classical bladder exstrophy-epispadias complex who were surgically repaired at our center between 2022 and 2025. Patients were divided into two groups according to PRF usage: PRF group, with PRF use (n = 12, 60%); non-PRF group (controls), without PRF use (n = 8, 40%); allocation concealment was reached using sequentially numbered, opaque, sealed envelopes opened during the surgery. In the PRF group, 5-10 mL of the patient's autologous venous blood was obtained intraoperatively and centrifuged at 3000 revolutions per minute for 10 min to produce a PRF clot, which was then transformed into a dense fibrin membrane. The fibrin was stitched with PDS 6/0 onto the bladder neck angle dorsally before the approximation of the pubic symphysis. All the steps of the procedure were conducted according to the sterility requirements. The patients from both groups underwent osteotomy anteriorly with fixation of a metal construction externally. The mean operative time and length of hospital stay were comparable between the two groups. In the non-PRF group, 3 (37.5%) patients and 1 (12.5%) patient had penopubic fistula and wound dehiscence, respectively. Compared to the control group, the PRF group patients were complication-free, demonstrating a favorable preliminary signal (p = 0.014). PRF is a simple, feasible adjunct for covering the bladder neck junction, as it suggests a potential signal toward reducing penopubic fistula formation. Due to the small sample size, these results are hypothesis-generating, and adequately larger randomized comparative studies are needed to confirm these exploratory findings.
2026-01-12 | Multidisciplinary perioperative management of cloacal exstrophy bladder closure: A single institution's approach.
Cloacal Exstrophy (CE), also known as OEIS complex (Omphalocele, Exstrophy of the cloaca, Imperforate anus, and Spinal defects), is the rarest and most severe congenital malformation of the bladder exstrophy-epispadias spectrum, characterized by an open bladder and exposed portions of the large intestine, along with bony anomalies. The objective of this study is to describe the experience of a high-volume exstrophy center's perioperative pathway, with a focus on analgesic use as well as urologic, orthopedic, and dietary interventions, for bladder repair of cloacal exstrophy. An IRB-approved, prospectively-maintained institutional approved Bladder Exstrophy-Epispadias Complex database was reviewed for patients with CE who had undergone bladder closure between 2017 and 2024. Electronic medical records were retrospectively reviewed to examine patient demographics, use of pelvic osteotomy, immobilization status, pediatric intensive care unit (PICU) admission, perioperative analgesia and sedation, nutritional support, drainage tubes, blood transfusion, antibiotic coverage, hospital length of stay, postoperative complications and closure failure. One hundred seventy-six CE and CE-variant patients were identified and 23 underwent bladder closure during this period. The median age at pelvic osteotomy was 1.93 years (IQR, 1.48-2.43, range 1-7). A delay of 14 days (IQR, 10-16) between osteotomy and closure was used in all but two patients. External fixation device and Buck's traction remained for 42 (IQR, 42-47) days. Post-closure, PICU stay was 8 days (IQR, 7-13) with 78 % requiring invasive ventilation for 4.5 days (IQR, 2-13.8). All patients required blood transfusions (2, IQR, 1-3). Enteral feeding resumed by day 11.5 (IQR, 5.8-16.5) for all but one and parenteral nutrition for 21 days (IQR, 13.5-53). Patient-controlled analgesia (PCA) was used in all patients for both pre- and post-closure, morphine most commonly (76 % and 48 %, respectively). Opioid use totaled 45 days (IQR, 40-60). Acetaminophen use was universal and NSAIDs used in 43 % (pre) and 57 % (post), clonidine in 62 % (pre) and 96 % (post). Bladder closure was successful in 87 %, while 13 % required repeat operation. Length of stay averaged 62 days (IQR, 51-86), range 42-191. While our study was limited by a small patient population, this data highlights the complexity and resource-intensive nature of CE bladder closure, emphasizing the need for comprehensive multidisciplinary management at specialized centers. Our 87 % success rate in bladder closure for patients with CE underscores the effectiveness of the multidisciplinary approach described when managing the complex perioperative course of these patients. However, challenges remain including prolonged hospitalization, ventilation requirements and slow reintroduction of enteral nutrition while highlighting the optimization of perioperative strategies of pain, sedation and recovery.
2025-09-28 | Anesthetic management with ultrasound-guided caudal epidural catheter for primary closure of vesical exstrophy in a neonate: Case report
ABSTRACT: The exstrophy-epispadias complex is a spectrum of congenital malformations in which the main predictor for functional adverse outcomes and higher health costs is failed primary closure. We present the case of a 13-day old new-born who underwent primary closure of bladder exstrophy under general anaesthesia. We highlight some factors of the perioperative anaesthetic approach that may have influenced the successful primary closure. These factors include fluid management guided by hemodynamic goals and multimodal analgesic management involving an ultrasound-guided caudal epidural catheter.
2025-03-25 | Covered exstrophy of the bladder, approaches to treatment.
Introduction. Classic bladder exstrophy is a rare anomaly, occurring in a ratio of 1:30000 to 1:50000 newborns. However, various variants of the exstrophy-epispadias complex are 10 times less common. Covered bladder exstrophy is a rare variant of classic exstrophy. Patients with the covered variant of exstrophy can be considered as classic exstrophy with all the accompanying defects of this anomaly, but with a bladder that is closed and covered only by a thin, often translucent skin membrane without muscles or a fascial layer. Cases in this category of patients may be underestimated in terms of the size of the defect at initial detection. Case report. The article describes two rare clinical observations of treatment of children with covered bladder exstrophy. A 5-year-old boy underwent a full range of surgical treatment: primary closure of the bladder, Cohen ureterocystoneoimplantation, bladder neck plastic surgery, bilateral iliac osteotomy, with reduction and fixation of the pubic bones. A 10-year-old girl underwent plastic surgery of the anterior abdominal wall, bilateral iliac osteotomy, and reduction (convergence) of the pubic bones. Conclusions. It is important to follow the principles of classical exstrophy correction in the treatment of children with covered bladder exstrophy. In the presence of symptoms of urinary incontinence, bladder neck reconstruction is indicated, this will improve continence and promote adequate bladder growth. Correct treatment of these malformations of the genitourinary system can significantly improve the quality of life of these patients.
2021-07-15 | Urothelial Differences in the Exstrophy-Epispadias Complex: Potential Implications for Management.
The authors examined the urothelium of exstrophy-epispadias complex spectrum patients for histological differences and expression of terminal markers of urothelial differentiation. Between 2012 and 2017 bladder biopsies were obtained from 69 pediatric exstrophy-epispadias complex patients. These specimens were compared to bladder specimens from normal controls. All bladder specimens underwent histological assessment followed by immunohistochemical staining for uroplakin-II and p63. Expression levels of uroplakin-II and p63 were then assessed by a blinded pathologist. Forty-three classic bladder exstrophy biopsies were obtained (10 newborn closures, 22 delayed closures, and 11 repeat closures). Additional biopsies from 18 cloacal exstrophy patients and 8 epispadias patients were also evaluated. These specimens were compared to 8 normal control bladder specimens. Overall, uroplakin-II expression was lower in exstrophy-epispadias complex patients compared to controls (p <0.0001). Among classic bladder exstrophy patients, there was reduced expression of uroplakin-II in the delayed and repeat closures in comparison to newborn closures (p=0.045). Expression of p63 was lower in patients with exstrophy-epispadias complex compared to controls (p <0.0001). Expression of p63 was similar among classic bladder exstrophy patients closed as newborns when compared to delayed or repeat closures. Classic bladder exstrophy patients had a higher rate of squamous metaplasia when compared to controls (p=0.044). Additionally, there was a higher rate of squamous metaplasia in the patients undergoing delayed closure in comparison to those closed in the newborn period (p <0.001). The urothelium in the exstrophy-epispadias complex bladder is strikingly different than that of healthy controls. Uroplakin-II expression is greatly reduced in exstrophy-epispadias complex bladders and is influenced by the timing of bladder closure. Reduced uroplakin-II expression and increased rates of squamous metaplasia in exstrophy-epispadias complex patients undergoing delayed closure suggests that exposure of the urothelium may induce these changes. These findings shed light on the molecular changes in exstrophy-epispadias complex bladders and may have implications on the appropriate timing of primary bladder closure, as those closed in the newborn period appear to have a greater potential for growth and differentiation.
antibodies
2023-12-08 | Urothelial carcinoma occurring in a defunctionalized bladder after urinary diversion due to the bladder exstrophy‐epispadias complex
Introduction The bladder exstrophy‐epispadias complex is a rare congenital disease. Urothelial carcinomas rarely occur in patients with this disease, and there have been few reports on its treatment. Case presentation We report the case of a 44‐year‐old man with a hemorrhage from the external urethral meatus. He was diagnosed with bladder exstrophy‐epispadias complex and underwent urinary diversion with substitution cystoplasty and Mitrofanoff appendicovesicostomy. Because computed tomography and magnetic resonance imaging suggested invasive bladder carcinoma in the defunctionalized bladder, we performed a cystectomy. The patient was diagnosed with urothelial carcinoma with glandular differentiation. One month after the surgery, nivolumab adjuvant chemotherapy was administered. The patient showed no signs of recurrence or metastasis after the treatment. Conclusion This is the first case of adjuvant nivolumab therapy for urothelial carcinoma with the bladder exstrophy‐epispadias complex.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Exstrophy-epispadias complex.
1 orphan drug designation for Exstrophy-epispadias complex.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Primary Human Satellite cell-derived muscle stem cells | cell therapies | FDA | — | MyoPax Denmark ApS |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.