Optimizing prenatal diagnosis and referral of classic bladder exstrophy: Lessons from a single-institution experience.

INTRODUCTION: Classic bladder exstrophy (CBE) is a malformation of the genitourinary system that occurs due to failure of abdominal wall closure. Unlike other malformations of similar incidence, prenatal diagnosis of CBE relies on suggested, rather than formal, diagnostic criteria. OBJECTIVE: This report describes prenatal diagnosis of CBE in the largest single-institutional cohort to date and delineates key sonographic findings and protocols for specialist referral. MATERIALS AND METHODS: A single-institutional database was reviewed for CBE patients born since 2000. Data on screening ultrasound use, gestational age at ultrasound, and abnormal findings were extracted. Where possible, time of prenatal diagnosis (pre- or postnatal and gestational age), ultrasound findings and other imaging data, specialist referral, institution of birth and closure, and outcome of primary closure attempt were compared. RESULTS: Of 557 patients born with CBE between 2000 and 2022, 284 met inclusion criteria and complete data were available for 280 (229 born domestically and 51 born internationally) who were included for analysis. Abnormal sonography suggestive of CBE was present for 48% (n = 134) of patients, for whom absent bladder was the most common abnormal finding (76% [102/134]). Of domestic patients, 46% (n = 106) were diagnosed prenatally at a median gestational age of 22 weeks (inter-quartile range [IQR]: 20-24), and 14% (n = 32) underwent confirmatory fetal magnetic resonance imaging. Of domestic patients with abnormal prenatal findings, 75% (n = 80/106) consulted with maternal-fetal medicine and 58% (n = 62/106) consulted with pediatric urology. On univariate analysis, prenatal diagnosis was positively associated with primary repair at Association for the Bladder Exstrophy Community-recognized centers of excellence (54% vs. 38%, p = 0.02) and negatively associated with osteotomy at primary closure (41% vs 59%, p = 0.003) but not success of primary closure (74% vs. 82%, p = 0.07). DISCUSSION: Rates of prenatal diagnosis in this cohort were similar to previous reports of smaller cohorts. Diagnosis allows for comprehensive pre- and postnatal follow-up with a pediatric urologist, with implications on birth planning and decisions on termination of pregnancy. Because of the previously-reported association between exstrophy and in vitro fertilization, these pregnancies should undergo detailed sonography. Any nonvisualization of the fetal bladder should prompt a detailed exam, and any finding characteristic of bladder exstrophy warrants referral to pediatric urology. CONCLUSIONS: Although CBE is a rare disorder, it is underdiagnosed during pregnancy. Sonographers and obstetricians should be aware of characteristic findings and best practices following diagnosis. Early referral to pediatric urology and maternal-fetal medicine is important for counseling and postnatal planning.

Perioperative management of primary classic bladder exstrophy: A single institutional pathway to success.

PURPOSE: Appropriate perioperative management is crucial in patients undergoing classic bladder exstrophy closure (CBE). Therefore, the authors sought to review their intra and postoperative management of patients with CBE undergoing primary closure and examine the impact of this pathway on patient outcomes. METHOD: A prospectively maintained institutional approved exstrophy-epispadias complex database was reviewed for patients with CBE who had undergone primary closure between 2016 and 2022 and whose closure was performed within one year of age. Electronic medical records for eligible patients were retrospectively reviewed to examine patient demographics, use of pelvic osteotomy, immobilization status, pediatric intensive care unit (PICU) admission and management, perioperative analgesia and sedation, nutritional support, drainage tubes, blood transfusions, antibiotic coverage, hospital length of stay, postoperative complications, and closure failure. RESULTS: A total of 25 patients were identified, 22 with CBE and 3 with variant CBE. Closure was performed at a median age of 84 days with patients ranging in age from 9 to 351 days. All patients underwent osteotomy and immobilization with modified Buck's traction and external fixation for a median duration of 41 days. A suprapubic tube was placed in all patients for a median duration of 46.5 days. All patients underwent PICU admission following closure for a median duration of 8 days. Ventilator support was required in 68 % of patients for a median of 3 days. Epidural analgesia was used in all patients and catheters were maintained for a median duration of 19 days. All patients received a blood transfusion over the course of their admission. Patient-controlled analgesia was used in most patients as an adjunct for a median duration of 38.5 days. Other commonly used analgesic adjuncts included acetaminophen, diazepam, clonidine, and dexmedetomidine. TPN was used in 80 % of patients for a median of 7 days with a return of oral feeding thereafter. Overall, the closure success rate in this cohort of patients was 100 %. DISCUSSION: The outcome of primary bladder closure can have inauspicious consequences that can affect a child's continence for years. The incidence of failed bladder closure can be minimized with the implementation of a detailed plan for immobilization, analgesia, and nutrition guided by an experienced multi-disciplinary team. CONCLUSION: We have identified several guiding principles for perioperative success in exstrophy patients at our center including Buck's traction with external fixation, provision of adequate postoperative analgesia and sedation, aggressive nutritional support, renal and bladder drainage, and robust antibacterial support. Our high success rate in managing this complex pathology demonstrates its validity and use as a pathway to success.

Interposing Rectus and Gracilis Muscle Flaps For Pelvic Reconstruction in Bladder Exstrophy After Bladder Neck Closure.

BACKGROUND: The exstrophy-epispadias complex is a spectrum of ventral wall malformations including classic bladder exstrophy (CBE) and cloacal exstrophy (CE). Patients undergo multiple soft-tissues procedures to achieve urinary continence. If unsuccessful bladder neck closure (BNC) is performed, muscle flaps may be used to reinforce BNC or afterwards for fistula reconstruction. In this study, patients reconstructed using a rectus abdominis or gracilis muscle flap were reviewed. METHODS: A retrospective cohort study of exstrophy-epispadias complex patients who underwent BNC and had a muscle fap was performed. Indication for flap use, surgical technique, risks for BNC failure including mucosal violations (MVs) were reviewed. MVs were prior bladder mucosa manipulation for exstrophy closure, repeat closure(s) and bladder neck reconstruction. Success was defined as BNC without fistula development. RESULTS: Thirty-four patients underwent reconstruction. Indications included during BNC (n=13), fistula closure after BNC (n=17), following BNC during open cystolithotomy (n=1) or fistula closure after open cystolithotomy (n=3). A vesicourethral fistula developed most frequently in CBE (88.9%) and vesicoperineal fistula in CE (87.5%). Thirty-three rectus flaps and 3 gracilis flap were used with success achieved in 97.1% and 66.7%, respectively. All 34 patients achieved success and 2 CE patients required a second flap. CONCLUSION: The rectus flap is preferred as it covers the antero-inferior bladder and pelvic floor to prevent urethral, cutaneous, and perineal fistula formation. The gracilis flap only reaches the pelvic floor to prevent urethral and perineal fistula development. Increased MVs, increase the risk of fistula formation and may influence the need for prophylactic flaps.

Multi-staged vs Single-staged Pelvic Osteotomy in the Modern Treatment of Cloacal Exstrophy: Bridging the Gap.

PURPOSE: Staged pelvic osteotomy has been shown in the past to be an effective tool in the closure of the extreme pubic diastasis of cloacal exstrophy. The authors sought to compare orthopedic complications between non-staged pelvic osteotomies and staged pelvic osteotomies in cloacal exstrophy. METHODS: A prospectively maintained exstrophy-epispadias complex database of 1510 patients was reviewed for cloacal exstrophy bladder closure events performed with osteotomy at the authors' institution. Bladder closure failure was defined as any fascial dehiscence, bladder prolapse, or vesicocutaneous fistula within one year of closure. There was a total of 172 cloacal exstrophy and cloacal exstrophy variant patients within the database and only closures at the authors' institution were included. RESULTS: 64 closure events fitting the inclusion criteria were identified in 61 unique patients. Staged osteotomy was performed in 42 closure events and non-staged in 22 closures. Complications occurred in 46/64 closure events, with 16 grade III/IV complications. There were no associations between staged osteotomy and overall complication or grade III/IV complications (p = 0.6344 and p = 0.1286, respectively). Of the 46 total complications, 12 were orthopedic complications with 6 complications being grade III/IV. Staged osteotomy closure events experienced 10/42 orthopedic complications while non-staged osteotomy closures experienced 2/22 orthopedic complications, however this did not reach significance (p = 0.1519). Of the 64 closure events, 57 resulted in successful closure with 6 failures and one closure with planned cystectomy. CONCLUSION: This study confirms, in a larger series, superior outcomes when using staged pelvic osteotomy in cloacal exstrophy bladder closure. Staged osteotomy was shown to be a safe alternative to non-staged osteotomy that can decrease the risk of closure failure in this group. Staged pelvic osteotomy should be considered in all patients undergoing cloacal exstrophy bladder closure. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.

The Effects of Growth Hormone on Nerve Regeneration and Alloimmunity in Vascularized Composite Allotransplantation.

BACKGROUND: Poor outcomes in functional recovery following upper extremity transplantation are largely due to denervation-induced muscle atrophy that occurs during the prolonged period of nerve regeneration. Growth hormone (GH) has well-established trophic effects on neurons, myocytes, and Schwann cells and represents a promising therapeutic approach to address this challenge. This study sought to confirm the positive effects of GH treatment on nerve regeneration and functional recovery and to evaluate the effects of GH treatment on the immune response in the setting of vascularized composite allotransplantation. METHODS: Rats underwent orthotopic forelimb transplantation across a full MHC-mismatch and received either porcine-derived growth hormone or no treatment (n=18 per group). Functional recovery was measured using electrically-stimulated grip strength testing. Animals were monitored for clinical and subclinical signs of rejection. RESULTS: Neuromuscular junction reinnervation and grip strength were improved in GH-treated animals (p=0.005; p=0.08). No statistically significant differences were seen in muscle atrophy, degree of myelination, axon diameter, and axon counts between groups. The rates of clinical and histological rejection did not significantly differ among groups. CONCLUSIONS: Our findings alleviate concern for increased risk of transplant rejection during GH therapy and therefore support the translation of growth hormone as a therapeutic method to promote improved functional recovery in upper extremity transplantation.

Mucosal Violations and Their Effect on Successful Bladder Neck Closure in Cloacal Exstrophy.

BACKGROUND: Cloacal exstrophy (CE) is rare and challenging to reconstruct. In the majority of CE patients voided continence cannot be achieved and so patients often undergo bladder neck closure (BNC). Prior mucosal violations (MVs), a surgical event when the bladder mucosa was opened or closed, significantly predicted failed BNC in classic bladder exstrophy with an increased likelihood of failure after 3 or more MVs. The aim of this study was to assess predictors for failed BNC in CE. METHODS: CE patients who underwent BNC were reviewed for risk factors for failure including osteotomy use, successful primary closure, and number of MVs. Chi-squared and Fisher's exact tests were used for comparing baseline characteristics and surgical details. RESULTS: Thirty-five patients underwent BNC. Eleven patients (31.4%) failed BNC including a vesicoperineal fistula in nine, vesicourethral and vesicocutaneous fistula in one each. The fistula rate in patients with 2 or more MVs was 47.4% (p = 0.0252). Two patients subsequently developed a vesicocutaneous fistula after undergoing repeated cystolithotomies. A rectus abdominis or gracilis muscle flap were used to close the fistula in 11 and 2 patients, respectively. CONCLUSIONS: MVs have a greater impact in CE with an increased risk of failed BNC after 2 MVs. CE patients are most likely to develop a vesicoperineal fistula while a vesicocutaneous fistula is more likely after repeat cystolithotomy. A prophylactic muscle flap should be considered at time of BNC in patients with 2 or more MVs. LEVELS OF EVIDENCE: Prognosis Study, Level III.

The impact of repeated bladder surgery on successful bladder neck closure in classic bladder exstrophy: The role of mucosal violations.

INTRODUCTION: Restoration of genitourinary anatomy with functional urinary continence is the reconstruction aim is the exstrophy-epispadias complex (EEC). In patients who do not achieve urinary continence or those who are not a candidate for bladder neck reconstruction (BNR), bladder neck closure (BNC) is considered. Interposing layers including human acellular dermis (HAD) and pedicled adipose tissue are routinely placed between the transected bladder neck and distal urethral stump to reinforce the BNC and minimize failure due to fistula development from the bladder. OBJECTIVE: The aim of this study was to review classic bladder exstrophy (CBE) patients who underwent BNC to identify predictors of BNC failure. Specifically, we hypothesize that increased operations on the bladder urothelium leads to a higher rate of urinary fistula. STUDY DESIGN: CBE patients who underwent BNC were reviewed for predictors of failed BNC which was defined as bladder fistula development. Predictors included prior osteotomy, interposing tissue layer use and number of previous bladder mucosal violations (MV). A MV was defined as a procedure when the bladder mucosa was opened or closed for: exstrophy closure(s), BNR, augmentation cystoplasty or ureteral re-implantation. Predictors were evaluated using multivariate logistic regression. RESULTS: A total of 192 patients underwent BNC of which 23 failed. Patients were more likely to develop a fistula with a wider pubic diastasis at time of primary exstrophy closure (4.4 vs 4.0 cm, p=0.0016), have failed exstrophy closure (p=0.0084), or have 3 or more MVs before BNC (p=0.0002). Kaplan-Meier analysis of fistula-free survival after BNC, demonstrated an increased fistula rate with additional MVs (p=0.0004, Figure 1). MVs remained significant on multivariate logistic regression analysis with a per-violation odds ratio of 5.1 (p<0.0001). Of the 23 failed BNC's, 16 were surgically closed including 9 using a pedicled rectus abdominis muscle flap which was secured to the bladder and pelvic floor. CONCLUSION: This study conceptualized MVs and their role in bladder viability. Increased MVs confer an increased risk of failed BNC. When considering BNC, CBE patients with 3 or more prior MVs may benefit from a pedicled muscle flap, in addition to HAD and pedicled adipose tissue, to prevent fistula development by providing wellvascularized coverage to further reinforce the BNC.

Bladder capacity and growth in classic bladder exstrophy: A novel predictive tool.

INTRODUCTION: Bladder capacity (BC) is an important metric in the management of patients with classic bladder exstrophy (CBE). BC is frequently used to determine eligibility for surgical continence procedures, such as bladder neck reconstruction (BNR), and is associated with the likelihood of achieving urinary continence. OBJECTIVE: To use readily available parameters to develop a nomogram that could be used by patients and pediatric urologists to predict BC in patients with CBE. STUDY DESIGN: An institutional database of CBE patients was reviewed for those who have undergone annual gravity cystogram 6 months after bladder closure. Candidate clinical predictors were used to model BC. Linear mixed effects models with random intercept and slope were used to construct models predicting log transformed BC and were compared with adjusted R2, Akaike Information Criterion (AIC), and cross-validated mean square error (MSE). Final model evaluated via K-fold cross-validation. Analyses were performed using R version 3.5.3 and the prediction tool was developed with ShinyR. RESULTS: In total, 369 patients (107 female, 262 male) with CBE had at least one BC measurement after bladder closure. Patients had a median of 3 annual measurements (range 1-10). The final nomogram includes outcome of primary closure, sex, log-transformed age at successful closure, time from successful closure, and interaction between outcome of primary closure and log-transformed age at successful closure as the fixed effects with random effect for patient and random slope for time since successful closure (Extended Summary). DISCUSSION: Using readily accessible patient and disease related information, the bladder capacity nomogram in this study provides a more accurate prediction of bladder capacity ahead of continence procedures when compared to the age-based Koff equation estimates. A multi-center study using this web-based CBE bladder growth nomogram (https://exstrophybladdergrowth.shinyapps.io/be_app/) will be needed for widespread application. CONCLUSION: Bladder capacity in those with CBE, while known to be influenced by a broad swath of intrinsic and extrinsic factors, may be modeled by the sex, outcome of primary bladder closure, age at successful bladder closure and age at evaluation.

The Role of Tissue Expanders in the Reconstruction of Proximal Hypospadias.

OBJECTIVE: To report the technique and outcomes of tissue expansion (TE) for generating additional penile skin for urethroplasty and/or skin coverage during primary or redo hypospadias repair in penoscrotal transposition (PST) patients with a proximal hypospadias. METHODS: Proximal hypospadias and PST patients with a lack of penile skin, congenitally or after failed repair, who underwent TE assisted reconstruction were reviewed. TE were placed under the penile shaft and expanded skin was used for tubularized incised plate repair. Success was defined as urethral advancement to the corona or more distal with tension free skin coverage. RESULTS: A total of 24 patients underwent reconstruction including 16 as part of primary repair and for redo repairs in 8. Nine patients experienced expander extrusion and posturethroplasty complications occurred in 43.8% of primary repairs and 75.0% of redo repairs; a urethrocutaneous fistula was most common (n = 8). Overall, success was achieved in 87.5% of patients with postoperative meatal locations almost all coronal (45.8%) or glanular (50.0%). CONCLUSION: Proximal hypospadias reconstruction is challenging, and complications are not infrequent. TE is a useful alternative for complex patients with a skin paucity such that cutaneous coverage would be difficult following urethroplasty. Although the complication rate was 43.8% for primary repair, TE generated sufficient residual skin for success after additional reconstruction. For redo repair early use is most beneficial as there is more expandable skin. The pseudocapsules provide vascularized coverage to reinforce the urethra while there is sufficient skin to minimize the need for a skin graft for penile coverage.

Surgical approach to penile reconstruction for shaft skin excision from circumcision.

PURPOSE: Circumcision is one of the most frequently performed surgical procedures. Complications are infrequent, including bleeding, though can be significant such as shaft skin excision. The aim of this study was to identify mechanism of injury and reconstructive techniques for skin excision using a full thickness skin graft (FTSG) or with the novel application of tissue expanders (TE). METHODS: Patients who underwent penile reconstruction following shaft skin excision from an overzealous circumcision were retrospectively reviewed. The penis was covered using a FTSG, harvested from the groin/hip, or using TE, with expanders placed in residual shaft skin. RESULTS: Twelve patients experienced significant skin loss (range 65-95%) including 2 with partial glans loss. Ten were reconstructed using a FTSG and 2 with TE. Injury was most frequently from a Mogen clamp (n = 9), or from a Gomco clamp, Plastibell device, and electrocautery burns. Six FTSG patients experienced complications with lymphedema (n = 3) most common. CONCLUSION: Shaft skin excision is a devastating complication with risk greatest from Mogen clamp use. TE is preferred as this avoids donor site morbidity which reassures parents but requires sufficient residual skin that can be expanded. Both techniques effectively provide soft tissue coverage with acceptable appearance and long-term function.

The use of a modified tanagho flap in the repair of posterior urethral stricture after primary exstrophy closure.

INTRODUCTION: In patients with classic bladder exstrophy (CBE), posterior urethral strictures after primary bladder closure can be difficult to manage and therefore necessitate alternative techniques in reconstruction of the proximal urethra. There is a paucity of literature describing treatment and management of posterior urethral stricture arising after repair of classic bladder exstrophy. OBJECTIVE: To describe the technique of a bladder neck reconstruction (BNR) with a modified Tanagho anterior detrusor flap in the treatment of posterior urethral stricture arising after repair of classic bladder exstrophy. PATIENTS AND METHODS: A prospectively maintained, IRB-approved database of 1401 exstrophy-epispadias patients was reviewed for patients who underwent bladder neck or proximal urethral reconstruction with modified Tanagho flap for proximal urethral stricture disease from the time period of 1975-2021. A total of 5 patients (1 female and 4 males) with classic bladder exstrophy who underwent proximal urethral reconstruction with modified Tanagho flap were identified. Of these 5 patients, the 1 female patient was treated for ongoing incontinence, not posterior urethral stricture, and was thus excluded from this report. Outcomes measured included post operative bladder capacity, post-operative continence status, upper urinary tract status, and stricture recurrence. RESULTS: Four male patients with CBE were treated for posterior urethral strictures and are reviewed here. Three patients underwent successful primary closure (1 via modern staged repair of exstrophy (MSRE) and 2 via complete primary repair of exstrophy (CPRE)), and 1 patient (MSRE) required repeat closure at the time of stricture repair. Mean age at BNR Tanagho flap was 3.8 (range 2.3-5.0) years. All patients remained stricture free with post-operative urinary incontinence; 2 patients underwent subsequent elective bladder neck transection to achieve continence. Mean follow up 9.9 (range 2.1-15.6) years. DISCUSSION: All 4 patients had excellent long term success rates, comparable to results reported in several adult studies utilizing a modified Tanagho flap in women with post-traumatic bladder neck contractures. In addition, our technique described here shares similarities with both the originally described Tanagho flap as well as with a dorsal onlay graft urethroplasty. CONCLUSION: In this limited series, modified Tanagho flap reconstruction is effective in treating posterior urethral stricture disease in CBE. This technique adds a valuable adjunct to the armamentarium of surgical options for this difficult to manage condition.

Application of Tunica Vaginalis Flap for Epispadias Repair in the Epispadias-Exstrophy Complex.

OBJECTIVE: To describe long-term outcomes and experience with the tunica vaginalis flap (TVF) as a tissue augment for complex epispadias repair. METHODS: A prospectively maintained institutional database was reviewed for patients who underwent epispadias repair with TVF from 2010 to 2021. Evaluation of patient characteristics between those who developed dehiscence or UCF and those who did not was performed via Mann-Whitney U, Kruskal-Wallis, or Fisher's exact test, as appropriate. RESULTS: A total of 47 male patients were identified, of whom, 1 (2.1%) had cloacal exstrophy, 38 (80.9%) had classic bladder exstrophy or a variant, and 8 (17.0%) had epispadias as their primary exstrophy-epispadias complex diagnosis. The median age at epispadias repair was 13 months (IQR 11 - 19). The overall rate of fistula or dehiscence development was 19.1% (9 patients), of whom, 7 developed urethrocutaneous fistulae, 1 dehiscence, and 1 both. Notably, 0 of the 5 patients who had undergone prior epispadias repair and 0 of the 8 patients with a diagnosis of isolated epispadias developed a UCF or dehiscence after repair with TVF. Differences in age at repair, primary EEC diagnosis, prior epispadias repair, pre-repair testosterone, fibrin sealant utilization, closure layers, stent removal time, and bladder capacity at repair were not statistically significant (P>.05) CONCLUSION: Our expanded evaluation indicates that utilization of the tunica vaginalis as an adjunct to epispadias repair may provide durable protection against fistula development in EEC patients who have undergone prior epispadias repair and in primary repair of patients with isolated epispadias.

Translational bioengineering strategies for peripheral nerve regeneration: opportunities, challenges, and novel concepts.

Peripheral nerve injuries remain a challenging problem in need of better treatment strategies. Despite best efforts at surgical reconstruction and postoperative rehabilitation, patients are often left with persistent, debilitating motor and sensory deficits. There are currently no therapeutic strategies proven to enhance the regenerative process in humans. A clinical need exists for the development of technologies to promote nerve regeneration and improve functional outcomes. Recent advances in the fields of tissue engineering and nanotechnology have enabled biomaterial scaffolds to modulate the host response to tissue repair through tailored mechanical, chemical, and conductive cues. New bioengineered approaches have enabled targeted, sustained delivery of protein therapeutics with the capacity to unlock the clinical potential of a myriad of neurotrophic growth factors that have demonstrated promise in enhancing regenerative outcomes. As such, further exploration of combinatory strategies leveraging these technological advances may offer a pathway towards clinically translatable solutions to advance the care of patients with peripheral nerve injuries. This review first presents the various emerging bioengineering strategies that can be applied for the management of nerve gap injuries. We cover the rationale and limitations for their use as an alternative to autografts, focusing on the approaches to increase the number of regenerating axons crossing the repair site, and facilitating their growth towards the distal stump. We also discuss the emerging growth factor-based therapeutic strategies designed to improve functional outcomes in a multimodal fashion, by accelerating axonal growth, improving the distal regenerative environment, and preventing end-organs atrophy.

Sexual health outcomes after penile reconstruction in the exstrophy-epispadias complex.

INTRODUCTION: The penis in exstrophy-epispadias complex (EEC) males is diminutive and patients are often dissatisfied with appearance and length. Due to an increased risk of psychosexual dysfunction, patients desire penile reconstruction. Surgical options include penile lengthening with a full thickness skin graft (SG) or tissue expansion (TE) used for cutaneous coverage or neophalloplasty using a radial forearm free flap or pedicled antero-lateral thigh flap. OBJECTIVE: The aim of this study was to assess sexual health outcomes before and after SG or TE assisted lengthening and neophalloplasty. STUDY DESIGN: Patients aged 18 years or older, who underwent penile reconstruction were identified using an institutionally approved database of EEC patients. Patient perception of penile appearance, sexual function, their frequency of sexual intercourse and overall satisfaction with reconstruction were assessed using a survey consisting of validated and non-validated questions. RESULTS: Eighty-three patients underwent penile reconstruction, 57 met the inclusion criteria and 28 responded to the survey (49.1%). Fourteen were reconstructed using a SG, 6 with TE and 8 underwent neophalloplasty. Median time from reconstruction to survey completion was 4.4 years (range 1.2-13.2) Four patients had a diagnosis of epispadias, 1 cloacal exstrophy, 23 classic bladder exstrophy (CBE). Before reconstruction patients were dissatisfied with their penile appearance with a median penile perception score of 4.5 compared to 7.5 after surgery (p = 0.0034, Fig. 1). Twenty-three patients were dissatisfied with penile length, with 18 reporting an improvement following reconstruction (p = 0.0002). There was no correlation in time after reconstruction with PPS or satisfaction with penile length (p = 0.86 and p = 0.55, respectively). Overall, the median Sexual Health Inventory for Men (SHIM) score was 19, with no difference between the surgical groups (p = 0.33). Nine patients engaged in sexual intercourse before reconstruction which increased to 17 afterwards. CONCLUSION: All three surgical methods improved patient perception of penile appearance and length. Patients who previously never engaged in intercourse were able to and those who had were doing so more frequently, of which a greater proportion were in a relationship. The results are encouraging though must be interpreted with caution due to the small number of responders and possible risk of bias. These findings provide vital information for future patients and routine psychological assessment will help manage patient expectations to improve satisfaction.

A Single Institutional Review of Periauricular Vestiges and Renal Anomalies: The Role of Screening Renal Ultrasonography.

ABSTRACT: Children with minor ear malformations including periauricular vestiges often undergo renal ultrasonography (RUS) to exclude renal anomalies associated with genetic conditions. The aim of this study is to assess the association between isolated periauricular vestiges and renal anomalies and delineate the indication for RUS in screening for renal anomalies. This is a retrospective review of infants who underwent surgical consultation for periauricular vestige excision to probe a possible relationship with renal anomalies. Patients with an isolated vestige were compared to patients presenting with additional clinical findings suggestive of a possible genetic disorder. A total of 150 infants underwent periauricular vestige excision; 47 were referred for RUS, 23 with no additional clinical findings, and 24 with periauricular vestiges in addition to other suspicious clinical and/or developmental findings. Of these 47 patients, 10 had renal anomalies: 4 (17.4%) with an isolated periauricular vestige had minor anomalies and 6 (25.0%) with a vestige plus suspicious clinical signs had 5 minor anomalies and one major anomaly. The odds of a patient with an isolated periauricular vestige having positive RUS findings were not significantly different than a patient with additional clinical findings having positive RUS findings (P = 0.72).The incidence of renal anomalies in infants with an isolated periauricular vestige was similar to that in patients with associated clinical signs suggestive of a possible genetic disorder. This was higher than the background population rate. Although most anomalies in patients with isolated ear findings were minor, our results suggest routine screening RUS should be considered.

Sustained IGF-1 delivery ameliorates effects of chronic denervation and improves functional recovery after peripheral nerve injury and repair.

Functional recovery following peripheral nerve injury is limited by progressive atrophy of denervated muscle and Schwann cells (SCs) that occurs during the long regenerative period prior to end-organ reinnervation. Insulin-like growth factor 1 (IGF-1) is a potent mitogen with well-described trophic and anti-apoptotic effects on neurons, myocytes, and SCs. Achieving sustained, targeted delivery of small protein therapeutics remains a challenge. We hypothesized that a novel nanoparticle (NP) delivery system can provide controlled release of bioactive IGF-1 targeted to denervated muscle and nerve tissue to achieve improved motor recovery through amelioration of denervation-induced muscle atrophy and SC senescence and enhanced axonal regeneration. Biodegradable NPs with encapsulated IGF-1/dextran sulfate polyelectrolyte complexes were formulated using a flash nanoprecipitation method to preserve IGF-1 bioactivity and maximize encapsulation efficiencies. Under optimized conditions, uniform PEG-b-PCL NPs were generated with an encapsulation efficiency of 88.4%, loading level of 14.2%, and a near-zero-order release of bioactive IGF-1 for more than 20 days in vitro. The effects of locally delivered IGF-1 NPs on denervated muscle and SCs were assessed in a rat median nerve transection-without- repair model. The effects of IGF-1 NPs on axonal regeneration, muscle atrophy, reinnervation, and recovery of motor function were assessed in a model in which chronic denervation is induced prior to nerve repair. IGF-1 NP treatment resulted in significantly greater recovery of forepaw grip strength, decreased denervation-induced muscle atrophy, decreased SC senescence, and improved neuromuscular reinnervation.