Bladder exstrophy: navigating long-term outcomes

Introduction

Bladder exstrophy (BE) is a rare congenital malformation of the lower genitourinary tract, abdominal wall, bony pelvis, genitalia, pelvic floor, spine, and anus within the spectrum of the exstrophy-epispadias complex (EEC). This spectrum ranges from cloacal exstrophy, the most severe form, to distal epispadias, in the mildest manifestations. The exact pathogenesis of BE remains unclear, however failure of cloacal membrane development and disrupted medial mesenchymal migration, have been implicated in resulting in its abnormal embryologic development (1). In males, an epispadic urethra covers the entirety of the dorsum of the penis, while in females, the clitoris is bifid and located next to the open urethral plate. Additionally, the vaginal opening is narrow and placed anteriorly on the perineum. The overall incidence of classical bladder exstrophy (CBE) in the United States is estimated to be 3.3 per 1,000,000 live births with a 2:1 male predominance (2).

The initial aim of repair of BE is successful bladder closure, preservation of the upper tract function, and a low-pressure reservoir, and acceptable genital cosmesis. Management begins shortly after birth and continues throughout life to optimize continence, physical function, body image, quality of life (QoL), and sexual function following anatomical reconstruction.

Achieving urinary continence remains one of the most significant challenges in BE management due to unique genitourinary anatomy, altered detrusor function, and variability of surgical success across repair techniques. Moreover, continence lacks a universal definition across studies, with reported outcomes varying based on parameters such as daytime dryness, nighttime dryness, and specified dry intervals. This lack of standardization makes cross-study comparisons difficult. Despite the void of consensus, certain predictors of continence have been identified including bladder capacity at the time of primary closure, success of initial closure, number of subsequent surgeries, and familial support- particularly in early years. Among these factors, bladder capacity is a critical metric by which closure options may be dictated, with larger capacities lending to increased likelihood of successful primary repair and small capacity ones may necessitate augmentation, or creation of a neobladder (3).

Despite advances in reconstructive techniques, functional and cosmetic outcomes following BE repair, continue to be a source of frustration for patients and their families (4). This dissatisfaction is especially pronounced following failure of primary repair, where additional surgeries become necessary, limiting reconstructive and continent options. Failure of primary repair is associated with higher rates of dissatisfaction, increased risk of upper tract deterioration and the need for subsequent surgical interventions to achieve for acceptable continent intervals.

Beyond continence, sexual satisfaction and reproductive health are critical considerations in patients as they transition from adolescent to adult. Male patients often experience shortened penile length and impaired ejaculatory function as a result of congenital anomalies and reconstructive interventions. Assisted reproductive technologies (ART) in the form of sperm extraction and intracytoplasmic sperm injection have expanded fertility options for these individuals. In female patients, anatomic abnormalities result in a shortened vagina, typically requiring vaginoplasty or introitoplasty for comfortable intercourse. Pregnancy is considered of high risk in this population, with higher-than-average rates of preterm delivery and spontaneous abortion (SAB) necessitating specialized care and planned cesarean sections (5,6).

Due to the low prevalence of BE and heterogeneity of treatment approaches, long term data regarding morbidity and complication management of adults with BE remains limited. However, the impact of BE is profound extending well beyond the operating room and adolescence, influencing continence, sexual function, fertility, and QoL. This review aims to summarize the available literature on management strategies used for common complications as patients transition out of pediatric care. Specifically, we will discuss the most common methods of BE repair, associated complication rates, the potential effects of repair on continence and sexual function in adults, and broader implications on their QoL.

Procedures, continence rates & complications

The two most common, and therefore most studied procedures are the complete primary reconstruction (CPRE) and the modern staged repair (MSRE). Other common methods of repair include the Kelly repair technique and, globally, additional techniques such as the Mainz Pouch II, Cologne pouch, bladder augmentation and continent urinary diversion using the Mitrofanoff principle (7). Despite early recognition and advancements in treatment options, many patients will still require augmentation to achieve satisfactory continence (8). As the method of repair is selected, the impact of complications and future continence must be considered. While literature on surgical and continence outcomes exists for these repair methods, these studies are often small, retrospective, and have variable observation periods. Few studies follow patients into adulthood, and definitions of “continence” vary considerably, making broad generalizations difficult. The primary goal of repair, regardless of the technique used, is the preservation of the upper renal tracts and the creation of a low-pressure reservoir.

The CPRE was introduced by Grady and Mitchell in 1989. This technique combines bladder closure with epispadias repair using disassembly of the penis. Mitchell et al. believed this method allowed cycling of the bladder, improving bladder growth and creation of outlet resistance (9). A systematic review by Pathak et al. revealed that 26% of patients managed with the CPRE technique between 1989 and 2018 had complications following primary closure. Of those patients 30% had a fistula, 13% had a failed closure, and 2 deaths were recorded (10). Shoukry et al. followed complications and continence outcomes in 51 patients at their institution over an average of 3 years after CPRE. This study had similar complication rates and found that 11.8% had a fistula and 15.6% had a complete failure of primary closure. Although their study showed 37% of patients were able to achieve continence, defined as dry for 2–3 hours during the day and completely dry at night, all of them required bladder augmentation (11). In a study by Mesrobian et al., the continence outcomes for 6 children were evaluated for a median of 5 years. The study found that 75% were able to achieve urinary continence, defined as a minimum dry interval of 1 hour (12).

Gearhart and Jeffs popularized the modern stage repair in 1989. This technique is completed in 3 sequential procedures: closure of the bladder template, posterior urethra, and abdominal wall by day 2 of life, epispadias repair at age 6–9 months, and bladder neck reconstruction (BNR) by time of continence training. Tourchi et al. evaluated 199 cases of BE treated with MSRE and found that 25% of their patients had history of closure failure and 87.6% had a successful bladder closure at their institution (13). Inouye et al. compared odds of failed closure in a cohort of 722 patients, finding that CPRE was twice as likely to result in failure in comparison of MSRE (14). Gargollo et al. found that 50% of their patients were continent, as defined by the International Children’s Continence Society’s classification, after completion of all three parts of MSRE (15). Shaw et al.’s review of 48 cases of BE repaired with MSRE demonstrated a continence rate of 23%, defined as dry for more than three hours during the day and all night, with primary closure, and 68% required further augmentation (16).

The radical soft tissue mobilization (RSTM) was introduced in the 1990s by Kelly. This technique is completed in two segments: bladder closure followed by dissection of the pelvis and corpora cavernosa to create a new posterior pelvic urethra. One benefit of RSTM is that it does not require osteotomy; however, technical challenged pose risks of damaging erectile tissue and lack of abdominal wall stability, especially during pregnancy in female patients (17,18). There have been three reported cases of ischemic penile injury following RSTM (19). In regards to continence, the original study by Kelly showed 37% of their patients were able to void volitionally; however, 26% were still completely incontinent 1 year after surgery (20). In a later case series of 14 patients, the abstract reports that 36% were fully continent, but no clear definition of continence was made (17). Similarly, Jarzebowski et al. reported that 70% of their patients treated with the Kelly technique were able to achieve at least partial continence, defined as dry for at least 2 hours and 3 or more night time wettings per month (21). A summary of continence rates and complications across the three mentioned techniques are provided in Table 1.

Notably, the techniques mentioned are primarily utilized in the developed world, whereas techniques like the Mainz Pouch offer relatively cost-effective urinary diversion options that may be suitable in resource limited setting where materials for routine catheterization pose a challenge (22). Continent urinary diversion strategies remain a treatment option, particularly following the failure of one of the previously mentioned exstrophy repair methods. The Mainz pouch II is one such approach utilizing a rectosigmoid pouch as a low-pressure reservoir, developed in 1983 by Thüroff. This repair technique eliminates the need for catheterization and is associated with high rates of both day and nighttime continence (23,24). Pahernik et al. studied a group of 38 children who underwent this procedure after failed primary reconstruction or an incontinent type of urinary diversion and found it to be a promising method for achieving continence. However, this technique is associated with a risk of malignancy at the uretero-intestinal anastomosis site (25).

Additional continent anal diversion options are available like the Cologne pouch procedure, allowing for the separate evacuation of urine and stool by connecting the bladder plate to the rectosigmoid pouch. In their evaluation of 29 patients, Klein et al. demonstrated that this technique resulted in continence for many patients. During the follow-up period, 22.2% of patients experienced a single urinary tract infection (UTI), 14.8% developed renal calculi, and none exhibited vesicoureteral reflux or stenosis (26). Bindi et al. illustrated the case of an 11-year-old girl who presented after primary repair with bilateral grade 3 reflux and complete incontinence, where the use of the Cologne pouch procedure resulted in urinary continence, an improved QoL, and no evidence of reflux or urinary infections within the study period (27). Creation of a continent catheterizable stoma (Mitrofanoff or appendiceal cystostomy) offers another option for management of incontinence in the patient with BE following repair. This procedure is completed in tandem with BNR or bladder neck closure to achieve continence (9,28). The Mitrofanoff procedure may also be used to ensure complete bladder emptying if voiding per-urethra is inadequate (29). These studies show that the creation of a catheterizable channel is an effective solution for bladder neck closure; however, its feasibility varies depending on lifestyle, social background, and/ or compliance of parents, and later patients.

Bladder management

The primary objective of repairing BE is to protect the upper tracts with successful closure of the bladder and reconstruct the genitalia with acceptable cosmesis. These aims require a competent functioning reservoir and an unobstructed urethra. The management of BE imposes a substantial burden on patients, representing one of the most complex pathologies for pediatric urologists. It involves close medical follow-up, multiple childhood surgeries, and potential social issues such as incontinence, scars, and physical differences from peers (30). A pediatric BE team might consist of a multidisciplinary group to address various aspects of care including a pediatric surgery unit and with contributors from orthopedic surgery, urology, anesthesiology, pediatrics, nursing, and social work. This comprehensive approach ensures all facets of the child’s condition are addressed, promoting better overall outcomes.

Continence

Urinary continence is a key goal in creating long-term QoL for patients following BE repair. However, determining continence can be difficult due to the lack of a universal definition, and varying patient expectations. Lottmann et al. found that factors such as early bladder closure, pelvic osteotomy, bladder reconstruction with bladder neck suspension in girls, and supportive social factors, were associated with long term continence but ultimate predictors of continence outcomes remain unclear (31). Achieving continence is not without its own challenges depending on the method used to achieve it, including risks of stenosis, recurrent infections, increased propensity for stone formation and the need for multiple bladder neck repairs.

Bladder capacity is a critical metric in the management of CBE, influenced by sex, the success and age of the initial bladder closure, and the age at evaluation. In the initial stages of repair, follow-up is centered on maintaining the functionality of a competent bladder or reservoir with an ability for patients to undertake voiding training while minimizing risk of injury to the upper urinary tracts. In surgical planning for continence procedures, higher bladder capacities may be associated with reaching voiding continence (32). However, prognosticating capacity using validated formulas such as the Koff formula are not validated for children with exstrophy due to quality and size of the detrusor muscle at birth. Factors such as the number of surgical interventions and differences in detrusor composition contribute to nonlinear growth of bladder capacity in BE patients. Some institutions may use cystoscopy to regularly evaluate capacity in BE patients, but urodynamic studies, remain an option, however their invasive nature and the need for sedation make them less ideal (33). There is no consensus or guideline to delineate the role of cystoscopy or urodynamics in determining capacity for children with BE.

For some patients, BNR is the most desirable continence surgery as it may allow patients to void per urethra. Current practice typically wait until BE patients have a capacity greater than 80–100 mL before pursuing BNR for continence (3). In the extended monitoring of individuals diagnosed with BE who underwent CPRE, Dy et al. found that 72% of females and 86% of males required BNR to achieve continence (5). Multiple studies show that successful primary closure is key for patients to develop sufficient bladder capacity to benefit from BNR and ultimately have improved likelihood of voiding continence (11,34). For those who are not ideal candidates for BNR whether due to capacity or history of multiple failed primary closures, continent diversion and bladder augmentation may be alternative options to attain dryness. A comprehensive analysis of bladder augmentation by Schlomer et al. revealed 10-year cumulative incidence rates for various complications, including bladder rupture (2.9–6.4%), small bowel obstruction (5.2–10.3%), bladder stones (13.3–36.0%), and re-augmentation (5.2–13.4%) (35). This surgical plan requires a capacity of at least 50 mL, with neobladder creation typically being performed for those with less than 50 mL of capacity (3). Active parental participation is critical regardless of bladder management strategy as adherence to strict catheterization or stoma care is paramount to maintain health of the upper renal tracts.

Urolithiasis and UTIs

One of the significant concerns in managing patients with BE is their increased risk of recurrent UTIs, and associated complications of stone formation, stenosis, and the risk of upper tract damage. Factors such as unique genitourinary anatomy, both secondary to the congenital anomaly of BE and resulting from surgical intervention, contribute to an increased risk of UTIs. Additionally, varying degrees of vesicoureteral reflux, incomplete emptying, and the requirement of catheterization all may accompany reconstruction further elevating this risk (36). Method of bladder repair does not appear to be indicative of UTI risk. In their survey of 159 patients, Villela et al. showed that in patients with continent urinary diversion, in the form of augmentation or neobladder, there was no difference in UTIs or recurrent UTIs although they were more likely to perform bladder irrigations (37).

Silver et al. demonstrated the incidence of urolithiasis in this patient population finding that most calculi were located in the bladder, with the most common composition being calcium apatite, calcium oxalate monohydrate and magnesium ammonium phosphate. Risk factors appeared to be associated with the divergent anatomy associated with reconstruction as well as UTI, foreign bodies, vesicoureteral reflux and urinary stasis (38). Other identified risk factors include undergoing augmentation cystoplasty and bladder neck procedure. The likelihood of developing stones within an augmented bladder is notably increased in the presence of BE, with an odds ratio of 17.4, possibly stemming from an underlying metabolic anomaly (39). Long term studies, such as that of Lottman et al., highlight common long-term sequelae of urogenital reconstruction. In this study, bladder stones were the most frequent complication, occurring in 23% of their cohort (31). Szymanski et al. found that of 85 patients with a bladder augmentation, approximately 70% of these stones were infectious and of those with an infectious stone, 70% of the recurrent stones were also infectious (40).

Carcinogenesis

One important concern for the long-term management of BE patients is the potential for malignancy, particularly due to the method of repair used, along with chronic irritation and infection of the bladder mucosa, which may increase cancer risk. Historically, ureterosigmoidostomy was used as a repair method for BE but was later found to be associated with several complications, notably malignancy of the colon. Research indicates that adults with BE face a 1–2% risk of malignancy within the bladder. Of Harris et al.’s 158 patients, 3 reported a history of bladder cancer and 2 reported prostate and urethral cancers illustrating the need for long term surveillance of this patient population (1,41). Adenocarcinoma is the most common type of cancer in BE cases, accounting for 95%, while squamous cell carcinoma accounts for only 3% to 5%. Transitional cell carcinoma, adenocarcinoma, and squamous cell carcinoma have all been observed in exstrophy bladders (42-45). Advances in reconstructive techniques and improved counseling on avoiding carcinogens may help reduce future risks. However, surveillance for bladder tumors remains challenging in this population, as their reconstructed urethras are often narrow, complicating procedures like cystoscopy in adulthood. Routine cystoscopy after bladder augmentation has not been found to be effective and no surveillance protocols have been established (1,41,44).

Male sexual health and fertility

An important issue as BE patients age is their long-term sexual function. Patients should feel welcome to discuss physical differences to limit embarrassment and promote a sense of normalcy (46). The most common penile issues reported are typically dorsal chordee and a short appearance. These concerns are well-recognized, and surgical solutions are increasingly accepted as standard practice. Regardless of whether they undergo cosmetic surgery, these patients typically have normal libido. A study by Sinatti et al. reports high rates of sexual engagement, with up to 96% of patients, and 79% of them reporting sexual satisfaction (47). Results regarding of sexual function are mixed. A study by Suominen et al. found that although males with a history of BE repair typically become sexually active later in life compared to age-matched controls, there were no differences in sexual function (30,48). If penile straightness is sufficient, many can engage in penetrative sexual activity. However, some males will require penile lengthening procedures to allow for penetrative intercourse. Nerli et al. reviewed cases of adolescent and adult male patients who sought genital reconstruction following earlier exstrophy repair (48). They found that the anterior corporal length in males with BE was about 50% shorter compared to normal controls, a finding originally described by Silver et al. (49). Among 14 patients who had undergone staged exstrophy repair in childhood, 11 had their repairs completed in an average of 3.9 stages (ranging from 3 to 5 stages). Seven of these 11 patients sought correction for dorsal chordee and penile lengthening, all presenting with a short, broad penis. The remaining four sought correction for chordee and removal of skin tags for cosmetic improvement.

Functional BNR, achieving proper anatomical placement of the colliculus seminalis in the posterior urethra, enabled antegrade ejaculation in 94.1% of patients (2). Applying staged exstrophy repair techniques can enhance both the cosmetic and functional outcomes of the genitourinary tract in patients with exstrophy. Modern exstrophy repair, however, poses potential complications of retrograde ejaculation which may hinder unassisted conception for males, though some studies indicate natural conception is possible. For example, a study by Sinatti et al. showed 67% of respondents who were men were able to father children with only one requiring reproductive technologies and 63% reported normal ejaculation following surgery (47). The advents of assisted reproductive therapies allow exstrophy patients with modern repair the ability to conceive children via testicular sperm extraction. This ability is illustrated by D’Hauwers et al. through three cases of having received a CPRE or MSRE in early childhood. Two were unable to produce spontaneous ejaculations, while one was able to ejaculate but could not participate in intravaginal coitus. In each case intracytoplasmic sperm injection procedures resulted in the birth of healthy newborns (6,50).

Female sexual health and fertility

As female patients with BE transition into adolescence and adulthood, sexual function and fertility become increasingly important. The anatomical impact of exstrophy often affects their reproductive organs, resulting in a shortened vagina in women. Modern, less invasive female genital reconstruction techniques aim to preserve the delicate nerve supply by leaving the split clitoris untouched to avoid scarring that could result from later re-dehiscence of the symphysis. Benz et al. demonstrated that, unlike the corpora cavernosa in boys, girls with BE have the majority of the clitoral body positioned anterior to the pelvic attachment (51). Cosmetic improvement in the mons pubis area are achieved by mobilizing adjacent inguinal tissue and rotating it medially into the affected area. Vaginoplasty is recommended for about two-thirds of these patients, and procedures such as episiotomy or introitusplasty using a Fortunoff-flap to prevent the need for repeated dilations during childhood. These interventions should ideally occur before or during puberty (18). In females, vaginal stenosis and Mullerian anomalies associated with BE may complicate intercourse (46).

High rates of sexual dysfunction have been reported in the adult population with a history of BE, including difficulties with arousal and orgasm, pain during intercourse, and dissatisfaction with genital appearance. Rubenwolf et al. conducted a study to assess the outcomes of sexual function and fertility in women with CBE who had undergone continent urinary diversion (50). Out of 38 eligible participants, 29 women (a response rate of 76%) with a follow-up period averaging 22.3 years were included in the analysis. Among these, 62% had primary continent urinary diversion, while 38% underwent secondary continent urinary diversion following unsuccessful initial reconstruction. The study found that sexual function, evaluated using the Female Sexual Function Index, was only slightly impacted across most domains, except for desire. The average total score on the Female Sexual Function Index was 28.4 out of a possible 36. Additionally, 31% of the women were identified as at risk for sexual dysfunction. Additionally, pelvic organ prolapse requiring surgical intervention occurred in 38% of the women.

Pelvic organ prolapse is frequently observed in females with BE and often manifests at a much younger age, irrespective of prior sexual activity or pregnancy. The prevalence is reported to be as high as 50%, attributed to the distinctive anatomical changes following pelvic reconstruction (39). These changes include an anterior vaginal introitus, posterior displacement of the dorsorectalis sling, weakened anterior compartment, deficient pelvic floor musculature and cardinal ligaments, and open ring due to symphyseal diastasis (52). Bujons et al. echoed genital prolapse as a noteworthy concern within this patient population, with a prevalence of 31% in the sample and up to 50% in other series (46). This issue becomes particularly pronounced during pregnancy, even though C-sections are employed for deliveries. Despite this precaution, BE patients are likely to experience some degree of genital prolapse, especially after a second pregnancy (30). Slings have shown success rates around 70%, while bulking agents provide short-term improvements in up to 60% of patients. The impact of pelvic osteotomies performed during bladder repair on subsequent pelvic organ prolapse remains debated, though they do not seem to significantly reduce the high rates of prolapse. There is, however, a noted correlation between the extent of pubic diastasis and the likelihood of future prolapse.

Women with EEC can have successful pregnancies, although they face increased risks of preterm delivery and SABs. In a study by Rubenwolf et al., 12 patients gave birth to 16 healthy children, with higher pregnancy rates observed in those who had primary continent urinary diversion compared to those who underwent secondary procedures (50). In their study, Dy et al. demonstrated that symptomatic UTIs, likely due to self-catheterization, were common in this specific cohort (5). Cesarean deliveries using a paramedian skin incision and classical uterine incision did not result in major complications. A multidisciplinary approach is essential for counseling females post-exstrophy repair, planning pregnancy, and ensuring timely referral to an adult urologist or gynecologist specializing in pelvic medicine and/or female reconstructive surgery.

QoL

While the aim of BE repair is to allow patients to live until adulthood with as few complications as possible, management of these patients remains a challenge. As patients with BE transition into adulthood, their QoL becomes an important aspect of care. While long-term QoL outcomes are scarce, the existing literature supports that the primary factors affecting QoL outcomes in adults include urinary incontinence and sexual dysfunction in addition to overall body image and self-esteem (35,39).

In a study by Wittmeyer et al., the QoL outcomes of 47 adult patients who underwent staged reconstruction for BE were evaluated using the Short Form-36 Medical Outcome Study questionnaire (SF-36) (53). The study found that the patients had lower QoL scores than normal controls, and that decreased scores were statistically different among patients depending on dryness, voiding, and urinary reconstruction/diversion. Himmler et al. compared the QoL outcomes of adult patients with BE who underwent either continent or incontinent urinary diversion procedures (54). This study found that patients with a history of BE, regardless of whether they had a continent or incontinent urinary diversion, had a significantly worsened incontinence-related QoL than the published reference group as measured by the SF-36 Survey and the Kings Health Questionnaire (KHQ). Similarly, Wiener et al. evaluated the long-term QoL outcomes of adult patients with BE. The authors suggest that compliance with a strict bladder emptying regimen or clean intermittent catheterization (CIC) have a negative impact on QoL for patients into adulthood (55).

Impacts of urinary incontinence and sexual dysfunction can have profound effects on self-esteem. A study by Bujons et al. found that for female patients with BE, the psychosocial impact of their condition is mainly accounted for by incontinence and gynecological complication (46). Despite facing challenges, adult female patients managed to attain a quasi-normal QoL, employing effective coping mechanisms. Notably, in the study by Bujons et al., the cohort’s academic and occupational accomplishments exceeded those of the general population, with every participant graduating from high school and around 50% pursuing higher education at the time (30). For male patients with BE, incontinence, erectile dysfunction, and dissatisfaction with genital appearance appear to have a considerable impact on self-esteem-related QoL (51). Rubenwolf et al. observed comparable sexuality and paternity outcomes in males over 18 with exstrophy who underwent urinary division, despite experiencing sexual dysfunction, when compared with men with preserved bladder function (50). Among the patients, 77% had achieved higher education, with 49% earning a degree. Furthermore, 73% were in stable partnerships, and 32% were married (56).

Strengths and limitations

The limitations of this research are inherent to the rarity of BE and the heterogeneity of its management. Drawing conclusions from the present studies is difficult due to limited available data, as well as variations in follow-up time interval, sample size, and outcomes. The retrospective nature of the data may introduce selection bias. Additionally, the lack of a uniform definition of continence complicates comparisons across studies, making it difficult to draw consistent conclusions. The strengths of this review lie in its ability to provide an expansive review of rare condition, one that has limited studies beyond pediatric years since these patients are now surviving well beyond historically reported lifespan. It shed light on long term complications that may become more apparent as these individuals age, enabling adult urologists to anticipate their care after transition. Lastly, this study highlights the need for long-term outcomes research to help formulate guidelines that will assist management of these complex cases.

Conclusions

A review of the literature shows advancements in BE reconstruction and remains one of the greatest challenges in pediatric urology. While these advancements have improved survival rates and functional outcomes, patients continue to face long term issues with sexual function and fertility. More research is needed to aid in individualized management and in forming a comprehensive and multidisciplinary care strategy.

Furthermore, the reviewed literature supports that BE is a complex condition that has a significant impact on the QoL of affected individuals into adulthood. BE and its associated procedures affect both physical and psychosocial domains of QoL, with challenges in areas such as continence, sexual function, body image, and self-esteem. However, the impact of the condition on QoL may be mitigated by early and multidisciplinary management, including surgical repair, rehabilitation, and psychosocial support. Nevertheless, further research is needed to better understand the long-term effects of BE on QoL and to develop more effective interventions for improving outcomes in affected individuals.

Acknowledgments

None.

Footnote

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2024-631/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2024-631/coif). B.M. has received consulting fees from ConMed and Arthrex; and has received Academic Funds for attending academic conferences. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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