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
574 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:
574 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:
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.
2025-06-14 | 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.
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.
2025-06-14 | 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.
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 | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Primary Human Satellite cell-derived muscle stem cells | cell therapies | FDA | 2023-07-13 | — | MyoPax Denmark ApS |
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