Prenatal Rupture of Hydrocolpos in a Cloacal Malformation.

INTRODUCTION: Cloacal dysgenesis occurs from failure of embryological division of urogenital sinus and hindgut, leading to a single common perineal opening for genitourinary and gastrointestinal tracts. The prenatal diagnosis of cloacal malformation is imprecise, but the clinical correlation of postnatal findings to prenatal history can help reveal explanations for unusual pathological findings in patients with urogenital abnormalities. CASE PRESENTATION: A 21-year-old woman was referred after her 20-week ultrasound demonstrated anhydramnios and concern for dilated fetal bowel. Fetal MRI confirmed anhydramnios and a dilated fetal colon, in addition to hydronephrosis and a pelvic cyst. Repeat ultrasound at 27 weeks showed unexpected complete resolution of her anhydramnios but new fetal ascites. The newborn girl was postnatally diagnosed with a cloacal malformation and an unusual near-complete fusion of her labia. She underwent proximal sigmoid colostomy and a tube vaginostomy at birth followed by cloacal reconstruction at 1.5 years old. CONCLUSION: In female fetus with a pelvic cyst, one should have a high index of suspicion for cloacal anomaly and consider the possibility of urinary obstruction leading to alteration in amniotic fluid.

Reoperation rates for stress urinary incontinence and pelvic organ prolapse in women after undergoing Mid-Urethral sling with or without concomitant colporrhaphy in academic centers within the United States.

In this study, the rates of reoperation for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) in women who underwent a mid-urethral sling (MUS) with or without concurrent colporrhaphy were evaluated. An academic faculty practice consortium database was used to identify a cohort of patients treated surgically for SUI with or without concurrent POP repair (apical, anterior, posterior, or a combination of the three) with or without hysterectomy between 2009 and 2011. A total of 20,484 patients matched the criteria. Of patients who underwent a MUS, 7.2% underwent secondary surgery, with a higher rate of 8.6% associated with those who underwent concurrent prolapse repair (Apical repair HR 1.84, p < .01; Anterior compartment repair HR 1.47, p < .01). Concurrent hysterectomy was associated with a lower hazard of secondary prolapse surgery (HR 0.48; p < .01) if the initial surgery involved a complete POP repair. Prolapse mesh repair resulted in a higher hazard of additional surgery (HR 1.43, p < .01). Medicaid insurance was also associated with an increased hazard ratio compared to commercial insurance for secondary surgery (HR 1.32, p < .01). For women undergoing MUS with complete prolapse repair, concurrent hysterectomy is associated with lower secondary surgery rates. Concurrent prolapse repair with mesh is associated with higher secondary surgery rates.Synopsis: For women undergoing MUS (mid-urethral sling) with complete prolapse repair, concurrent hysterectomy is associated with lower secondary surgery rates. Concurrent prolapse repair with mesh is associated with higher secondary surgery rates.Impact StatementWhat is already known on this subject? Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) can present at the same time and negatively impact patients' quality of life. There is little data regarding reoperation rates for patients who undergo both MUS and colporrhaphy in one setting.What do the results of this study add? This study found that patients who undergo concurrent MUS (mid-urethral sling) and complete POP repair with the addition of hysterectomy had a lower risk of secondary surgery.What are the implications of these findings for clinical practice and/or further research? Our data can be used by surgeons to counsel patients on the risks of re-operation for SUI for those who would like to undergo concurrent POP repair with or without hysterectomy.

Reoperation after Hypospadias Repair: Long-Term Analysis.

PURPOSE: While the true incidence of secondary hypospadias repair is unknown, the current literature cites a 3.3% to 6.7% reoperation rate after distal hypospadias repair and an association with age. We hypothesized that secondary surgery rates are associated with patient factors and have been underreported due to limited followup. MATERIALS AND METHODS: We used an academic practice plan consortium database to identify a population that underwent primary hypospadias repair in 2009 and 2010. Secondary surgeries between 2009 and 2019 were captured. The association of variables such as age, insurance type, region, surgeon volume and surgeon years in practice with all-inclusive and specific secondary surgery procedures were analyzed using mixed effects multiple logistic regression models. RESULTS: We identified 5,178 boys who had primary hypospadias repair performed by 84 pediatric urologists at 46 hospitals in 2009 and 2010. During the ensuing 9 to 10 years, distal, proximal and perineal hypospadias repair had a 12.6%, 37.9% and 46.6% rate of secondary surgery, respectively. After adjusting for all other variables in the model, patients with noncommercial insurance had a 26% (OR 1.26, p=0.04) increased odds of secondary surgery. Patient age and surgeon years in practice were not associated with all-inclusive secondary surgery except for endoscopic treatment. Surgeon volume was not associated with secondary surgery. CONCLUSIONS: This study demonstrated that secondary surgery rates are underreported if followup is limited to less than 6 years. Patient age, surgeon volume and experience did not associate with all-inclusive reoperation rates whereas insurance status was a major predictor of reoperation.

A New Appendicostomy Technique to Prevent Stomal Stenosis.

PURPOSE: Stomal stenosis has been reported to occur in 12% to 45% of patients following Malone antegrade continence enema and Mitrofanoff appendicostomy. The standard stoma technique entails excision of the distal appendix. We evaluated a novel technique with preservation of the appendiceal tip and vessels, and opening the lumen in a more proximal and vascular area to determine whether the incidence of stenosis would be decreased. MATERIALS AND METHODS: Medical records of patients who underwent appendicostomy for Malone antegrade continence enema or urinary diversion were retrospectively evaluated. We included cases with a minimum of 1 year of followup and those in which the distal portion of a complete appendix was oriented for use as the stomal end in the umbilicus. Variables such as age, gender, body mass index, antegrade continence enema or urinary diversion, open or laparoscopic approach, cecal and appendiceal adhesions, retrocecal position, cecal imbrication, technique and stenosis were recorded. Cox proportional hazards analyses were performed to determine association of covariates. RESULTS: A total of 123 patients met inclusion criteria. The incidence of stenosis following standard stoma technique was 13% (12 of 93 patients) with a median followup of 9.4 years. Of these cases 75% occurred within 1 year of surgery. Stomal stenosis did not occur after the new stoma technique in 30 patients with a median followup of 3.3 years. Only technique cohort (standard vs new) was associated with stenosis (p=0.04). CONCLUSIONS: Stomal stenosis of appendicostomy may be lessened by preservation of the distal appendiceal vasculature and tip, and opening the lumen in a more proximal location.

Pictorial Urgency Scale: A New Tool for Evaluating Bladder Urgency in Children.

PURPOSE: Bladder fullness and urgency are difficult for some patients to express. We hypothesized that images on a pictorial urgency scale would correlate with International Continence Society standard verbal descriptors and bladder volume. MATERIALS AND METHODS: The study population consisted of 267 toilet trained children with a mean age of 7.2 years and their parents (91 adults). Patients were excluded if they had a history of urinary infection, voiding dysfunction, genitourinary surgery or reflux. Participants were read each of the 4 descriptors and asked to point to an image. Correlation between descriptors and figures was analyzed using a mixed effects proportional odds logistic regression model (aim 1 of study). In addition, 73 children undergoing voiding cystourethrography were asked to point to the images during bladder filling. Correlation between percent of expected capacity and image was analyzed using a linear mixed effects model (aim 2 of study). RESULTS: Correlation between descriptors and images (aim 1) was 0.87 (95% CI 0.84 to 0.89) for all participants, 0.84 (95% CI 0.81 to 0.88) for patients younger than age 6 years and 0.88 (95% CI 0.85 to 0.90) for patients 6 to 17 years old. Sequencing of the images was appropriate for increasing degree of urgency. In 73 children undergoing voiding cystourethrography correlation between image and percent of expected capacity (aim 2) was 0.75 (95% CI 0.67 to 0.81, p <0.001). CONCLUSIONS: Figures on the pictorial urgency scale correlate with standard verbal descriptors and bladder volume. The pictorial scale could be a supplemental tool to improve communication of urgency sensation in younger children.

Surgical trends in the correction of female stress urinary incontinence in academic centers within the United States.

AIMS: There is a lack of data describing the current state of stress urinary incontinence (SUI) procedures in academic centers. Urologists, gynecologists, and urogynecologists perform these operations, but the relative volume each group accounts for is unknown. The purpose of this study was to evaluate the distribution of cases in academic centers between specialties and associated patient characteristics. METHODS: A hospital consortium database was used to identify patients treated surgically for SUI between 2009 and 2014. Patient and surgeon variables were evaluated. Patient variables (age, region, insurance, race) and surgeon volume were analyzed. Sub-analysis was conducted to determine concomitant prolapse repairs. RESULTS: Of the 50,315 stress urinary incontinence procedures performed, 22% were performed by urologists. Overall volume dropped 39% and mean surgeon volumes for all three groups decreased with time. Average median volume for urogynecologists (29/year) differed from both urologists (3/year) and non-urogynecologists (2/year). There was a significant difference in rate of concomitant prolapse repairs performed by urogynecologists (56%), gynecologists (54%), and urologists (26%). CONCLUSIONS: These data portray the changing pattern of SUI procedure practice in academic centers. Academic urologists are performing less than 25% of SUI procedures, with an overall decline in number of procedures across all specialties. Urogynecologists and gynecologists are performing a significantly higher proportion of concomitant prolapse repairs. Neurourol. Urodynam. 36:394-398, 2017. © 2015 Wiley Periodicals, Inc.

Urological Outcomes of Myelomeningocele and Lipomeningocele.

PURPOSE OF REVIEW: Spina bifida is caused by incomplete neural tube closure during the first trimester. This condition may lead to bowel and bladder dysfunction as well as truncal weakness and motor anomalies. Presentations vary between myelomeningoceles and lipomeningoceles and may result in different outcomes. This review seeks to explore our current understanding of the variations in outcomes between individuals with myelomeningocele and lipomeningocele. RECENT FINDINGS: Prenatal intervention has become a standard of care for prenatal diagnoses of myelomeningocele and has been shown to reduce shunt placement and improve motor skills. However, urological benefit from early intervention remains to be seen. Early surgical repair, however, may be beneficial for patients with lipomeningocele. Literature on the urological outcomes of patients with myelomeningocele and lipomeningocele is lacking. Further research is needed to better elucidate differences in long-term urological outcomes between these two pathologies.

Congenital adrenal hyperplasia: current surgical management at academic medical centers in the United States.

PURPOSE: Controversy exists on the necessity for and timing of genitoplasty in girls with congenital adrenal hyperplasia. Our knowledge of surgical preferences is limited to retrospective series from single institutions and physician surveys, which suggest a high rate of early reconstruction. We evaluated current surgical treatment for congenital adrenal hyperplasia at academic centers. MATERIALS AND METHODS: We queried the Faculty Practice Solutions Center database to identify all female patients younger than 18 years with a diagnosis of congenital adrenal hyperplasia between 2009 and 2012. Procedures were identified by CPT codes for vaginoplasty, clitoroplasty and other genital procedures. Reconstruction type, age at surgery and surgeon volume were analyzed. RESULTS: We identified 2,614 females in the database with a diagnosis of congenital adrenal hyperplasia who were seen at a total of 60 institutions. Of infants younger than 12 months between 2009 and 2011 as few as 18% proceeded to surgery within a 1 to 4-year followup. Of those referred to a pediatric urologist 46% proceeded to surgery. Of patients who underwent surgery before age 2 years clitoroplasty and vaginoplasty were performed in 73% and 89%, respectively, while 68% were treated with a combined procedure. A medium or high volume surgeon was involved in 63% of cases. CONCLUSIONS: Many patients with congenital adrenal hyperplasia in the database did not proceed to early reconstructive surgery. Of those referred to surgeons, who were possibly the most virilized patients, about half proceeded to early surgery and almost all underwent vaginoplasty as a component of surgery. About two-thirds of the procedures were performed by medium or high volume surgeons, indicative of the surgical centralization of disorders of sexual development.

Physician preference is a major factor in management of vesicoureteral reflux.

BACKGROUND: Known factors affecting the management of vesicoureteral reflux (VUR) include reflux grade, infection frequency, age and gender. We hypothesized that provider preference is highly associated with management. METHODS: Utilizing the national billing database, Faculty Practice Solutions Center, a multivariable logistic regression model, was applied to analyze the association of pediatric urologist treatment patterns, patient age, gender, uni- or bilateral disease, insurance type, presence of nephropathy and race with the type of VUR treatment a patient would receive. RESULTS: We identified 59 pediatric urologists who managed 7,882 new reflux patients from 2009 to 2011. Over this 3-year period there was wide variation in surgical utilization between surgeons (mean 50 %) but minimal change for each surgeon (5 %). For every 100 new reflux patients, median utilization of reimplantation surgery and injection of dextranomer/hyaluronic acid copolymer (Deflux) was 26 and 20 %, respectively. Age ranked highest in predicting surgical versus non-surgical management, while a surgeon's historic Deflux utilization rate ranked highest in predicting surgery type. Older age, female gender and white race also increased the odds of Deflux utilization over reimplantation. CONCLUSIONS: A surgeon's historic Deflux utilization was the most important predictor of VUR surgery type. Although data on reflux grade were not available, analysis of patient and surgeon characteristics suggests that surgeon preference is the first or second most critical factor in determining a patient's treatment.

Production of urothelium from pluripotent stem cells for regenerative applications.

As bladder reconstruction strategies evolve, a feasible and safe source of transplantable urothelium becomes a major consideration for patients with advanced bladder disease, particularly cancer. Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are attractive candidates from which to derive urothelium as they renew and proliferate indefinitely in vitro and fulfill the non-autologous and/or non-urologic criteria, respectively, that is required for many patients. This review presents the latest advancements in differentiating urothelium from pluripotent stem cells in vitro in the context of current bladder tissue engineering strategies.

Urinary diversion during and after pediatric pyeloplasty: a population based analysis of more than 2,000 patients.

PURPOSE: We evaluated the use and efficacy of intraoperative urinary diversion with ureteral stent or nephrostomy tube during pyeloplasty in children. MATERIALS AND METHODS: The Faculty Practice Solutions Center® national billing database was queried to identify all pediatric pyeloplasties performed from 2009 to 2012. Patient variables, surgical approach, use of intraoperative stent/nephrostomy tube and return for postoperative stent/nephrostomy tube or second pyeloplasty were obtained. RESULTS: A total of 2,435 children underwent open (1,792) or laparoscopic/robotic (643) pyeloplasty, with intraoperative urinary diversion rates of 45% and 83%, respectively. Comparing patients with and without an intraoperative stent/nephrostomy tube, 5.6% and 7.4%, respectively, returned to the hospital for urinary diversion. Multivariable analysis revealed no association with surgical approach, but higher surgeon volume (p <0.01) and use of an intraoperative stent/nephrostomy tube (p <0.01) were associated with decreased odds of requiring postoperative urinary diversion. Second pyeloplasty rate was 3.8% and was not associated with surgical approach or use of intraoperative stent/nephrostomy tube. CONCLUSIONS: Intraoperative stent/nephrostomy tube use and increased surgeon volume were each independently associated with a significant but small decrease in risk of postoperative stent/nephrostomy tube placement. Use of an intraoperative stent/nephrostomy tube was not associated with rate of second (redo ipsilateral or contralateral metachronous) pyeloplasty.

Predictors of secondary surgery after hypospadias repair: a population based analysis of 5,000 patients.

PURPOSE: The literature on secondary surgery after hypospadias repair is limited. We determined risk factors for secondary surgery via a population based approach. MATERIALS AND METHODS: We used a hospital consortium database to identify a population that underwent hypospadias repair in 2009 and 2010. Specifically meatal advancement and glanuloplasty, distal, proximal and perineal hypospadias repairs were evaluated. Secondary surgeries performed between 2009 and 2011 were captured and the variables of age at primary surgery, insurance, region and surgeon volume were measured. Mixed effects logistic regression analysis was used to analyze independent variables associated with secondary surgery. RESULTS: We identified 5,326 subjects who underwent primary hypospadias repair by 114 surgeons at 47 hospitals in 2009 and 2010. Distal hypospadias repair is associated with a 9% secondary surgery rate. After adjusting for other factors every additional 10 distal repairs that a surgeon performed yearly was associated with a 29% decreased risk of requiring fistula, stricture or diverticulum repair. There were regional differences for secondary surgery following meatal advancement and glanuloplasty and distal repairs. Finally, each additional year of patient age at distal repair was associated with a 15% increased risk of requiring secondary cystoscopy and a 21% increased risk of requiring urethral dilation/incision. CONCLUSIONS: This population based study produced significantly different results than small studies of select patients and techniques. Distal hypospadias repair is associated with a 9% secondary surgery rate. Low surgeon volume independently increases the risk of fistula, stricture or diverticulum repair. Increased patient age at primary distal hypospadias repair increases the risk of cystoscopy and urethral dilation/incision.

Pre-operative factors associated with the development of distal ureteral stump syndrome after upper pole heminephrectomy.

INTRODUCTION: For children with duplex systems and severe hydroureteronephrosis of the upper pole, heminephrectomy is one of many suitable treatments, particularly if there is no associated lower pole reflux. Distal ureteral stump syndrome (DSS) is a very difficult complication and manifests as stump empyema, urinary tract infection and/or vulvar discharge and can occur months to years later in 10-20 percent of patients. Secondary distal ureterectomy is an extremely difficult surgery due to inflammation and adhesions. To avoid DSS, distal ureterectomy at the time of heminephrectomy can be performed concurrently but carries a risk of lower pole ureter devascularization and injury. Current literature on DSS has shown associations with subtotal ureterectomy or long ureteral stumps. We hypothesized that there may be preoperative variables prior to heminephrectomy that are associated with the development of DSS. OBJECTIVE: Identify pre-operative risk factors for the development of DSS in pediatric patients who underwent upper pole heminephrectomy for duplex kidneys. STUDY METHODS: Retrospective analysis of pediatric patients who underwent upper pole heminephrectomy at single, academic institution from 1999 to 2021. Pre-operative patient age, gender, history, imaging, and lab results were extracted from patient charts to assess for factors that may predict the development of DSS. Patient groups with and without DSS were compared using Fischer's Exact Test. RESULTS: Five (14%) of 36 patients developed DSS and required secondary distal ureterectomy at a median time of 22 months (IQR 6-27) after heminephrectomy. The presence of ureteral debris (80% of DSS) on preoperative ultrasound (p < 0.001), reflux into the upper pole (p = 0.005), and mucus discharge (100% of DSS) (p < 0.001) prior to surgery were found to be significantly associated with those who developed DSS, compared to those who did not. These three pre-operative factors had high specificity (97-100%) and negative predictive value (94-97%). DISCUSSION: Substantial experience has shown that less than 20% of patients benefit from distal ureterectomy during upper heminephrectomy. Whether using an open or laparoscopic approach, selection of at-risk patients should lower operative time and avoid injury and devascularization of the lower pole ureter for most patients. CONCLUSION: The presence or absence of ureteral debris, mucus discharge and/or upper pole reflux prior to heminephrectomy may be useful guides in selecting which patients would benefit from concurrent distal ureterectomy and conversely which patients may safely avoid the additional dissection.

Impact of caudal block on revision rates after hypospadias repair: Multi-institution review.

INTRODUCTION: There is controversy surrounding the association between caudal block and complication rates after hypospadias repair. Conflicting results have been reported mostly from single-center, low volume studies and those that did not include relevant variables. OBJECTIVES: We hypothesized that caudal block is not associated with increased rates of reoperation after primary repair and is associated with more complex hypospadias surgery. STUDY DESIGN: The Clinical Practice Solutions Center database was queried to identify patients who received a primary hypospadias repair between 2009 and 2010. Primary hypospadias repair was further categorized as meatal advancement and glanduloplasty, distal, one-stage proximal, or one-stage perineal repair. Anesthesia coding was evaluated to identify those who received a caudal block. Any revision surgery was captured between 2009 and 2019 and the types of revision surgeries were identified. Variables such as caudal block, age, insurance type, surgeon volume, and surgeon years in practice were analyzed with mixed effects multiple logistic regression models. RESULTS: The dataset query identified 3343 pediatric males who had primary hypospadias repair. The procedures were performed by 50 surgeons at 27 hospitals. Primary surgeries included meatal advancement and glanduloplasty (23%), distal (69%), proximal (6.9%), and perineal repairs (1%). Caudal block was administered to 42% of patients. Utilization of caudal block was not associated with type of primary surgery (p = 0.21). Adjusting for all other variables, increased patient age was associated with decreased usage of caudal block (p < 0.001). Analysis did not demonstrate a statistically significant association between utilization of caudal block with rates of revision surgery. CONCLUSIONS: This large, multi-institution study demonstrates that the use of caudal block was not associated with more complex hypospadias surgery nor statistically significantly associated with increased rates of revision surgery after primary hypospadias repair.

Using uniaxial tensile testing to evaluate the biomechanical properties of bladder tissue after spinal cord injury in rat model.

To investigate the biomechanical properties of rat bladder tissue after spinal cord injury (SCI) using uniaxial tensile testing. Evidence suggests the bladder wall undergoes remodeling following SCI. There is limited data describing the biomechanical properties of bladder wall after SCI. This study describes the changes in elastic and viscoelastic mechanical properties of bladder tissue using a rat model after SCI. Seventeen adult rats received mid-thoracic SCI. Basso, Beattie, and Bresnahan (BBB) locomotor testing was performed on the rats 7-14 days after injury quantifying the degree of SCI. Bladder tissue samples were collected from controls and spinal injured rats at 2- and 9-weeks post-injury. Tissue samples underwent uniaxial stress relaxation to determine instantaneous and relaxation modulus as well as monotonic load-to failure to determine Young's modulus, yield stress and strain, and ultimate stress. SCI resulted in abnormal BBB locomotor scores. Nine weeks post-injury, instantaneous modulus decreased by 71.0% (p = 0.03) compared to controls. Yield strain showed no difference at 2 weeks post-injury but increased 78% (p = 0.003) in SCI rats at 9 weeks post-injury. Compared to controls, ultimate stress decreased 46.5% (p = 0.05) at 2 weeks post-injury in SCI rats but demonstrated no difference at 9 weeks post-injury. The biomechanical properties of rat bladder wall 2 weeks after SCI showed minimal difference compared to controls. By week 9, SCI bladders had a reduction in instantaneous modulus and increased yield strain. The findings indicate biomechanical differences can be identified between control and experimental groups at 2- and 9-week intervals using uniaxial testing.

Identifying variability in surgical practices and instrumentation for hypospadias repair across the Western Pediatric Urology Consortium (WPUC) network.

BACKGROUND: Although hypospadias outcomes studies typically report a level or type of repair performed, these studies often lack applicability to each surgical practice due to technical variability that is not fully delineated. An example is the tubularized incised plate (TIP) urethroplasty procedure, for which modifications have been associated with significantly decreased complication rates in single center series. However, many studies fail to report specificity in techniques utilized, thereby limiting comparison between series. OBJECTIVE: With the goal of developing a surgical atlas of hypospadias repair techniques, this study examined 1) current techniques used by surgeons in our network for recording operative notes and 2) operative technical details by surgeon for two common procedures, tubularized incised plate (TIP) distal and proximal hypospadias repairs across a multi-institutional surgical network. STUDY DESIGN: A two-part study was completed. First, a survey was distributed to the network to assess surgeon volume and methods of recording hypospadias repair operative notes. Subsequently, an operative template or a representative de-identified operative note describing a TIP and/or proximal repair with urethroplasty was obtained from participating surgeons. Each was analyzed by at least two individuals for natural language that signified specified portions of the procedure. Procedural details from each note were tabulated and confirmed with each surgeon, clarifying that the recorded findings reflected their current practice techniques and instrumentation. RESULTS: Twenty-five surgeons from 12 institutions completed the survey. The number of primary distal hypospadias repairs performed per surgeon in the past year ranged from 1-10 to >50, with 40% performing 1-20. Primary proximal hypospadias repairs performed in the past year ranged from 1-30, with 60% performing 1-10. 96% of surgeons maintain operative notes within an electronic health record. Of these, 66.7% edited a template as their primary method of note entry; 76.5% of these surgeons reported that the template captures their operative techniques very or moderately well. Operative notes or templates from 16 surgeons at 10 institutions were analyzed. In 7 proximal and 14 distal repairs, parameters for chordee correction, urethroplasty suture selection and technique, tissue utilized, and catheter selection varied widely across surgeons. CONCLUSION: Wide variability in technical surgical details of categorically similar hypospadias repairs was demonstrated across a large surgical network. Surgeon-specific modifications of commonly described procedures are common, and further evaluation of short- and long-term outcomes accounting for these technical variations is needed to determine their relative influence.

Detailed assessment of stomal incontinence after Malone antegrade continence enema: development of a new grading scale.

PURPOSE: The Malone antegrade continence enema procedure improves quality of life for patients with bowel dysfunction. Stomal leakage has been reported, although no objective scale describes this type of incontinence. The value of cecal imbrication has not been fully elucidated on a large scale. MATERIALS AND METHODS: We retrospectively reviewed pediatric patients who underwent Malone antegrade continence enema by a single surgeon between 2000 and 2010. Detailed information regarding degree and frequency of stomal incontinence was longitudinally recorded and analyzed. A classification system was developed, with grade 0 defined as no stomal incontinence, grade 1 a drop at the stoma or spotting on clothes 1 time or less per month, grade 2 spotting on clothing 2 to 4 times per month and grade 3 any leakage greater than 4 times per month. RESULTS: The Malone antegrade continence enema procedure was laparoscopic nonimbricated in 51 patients, open nonimbricated in 16 and open imbricated in 12. Mean followup was 3.5 years. Of cases where the appendix was not imbricated stomal incontinence was grade 0 in 69%, grade 1 in 19%, grade 2 in 7.5% and grade 3 in 4.5%. Two patients (3%) requested revision due to stomal incontinence. No patient who underwent Malone antegrade continence enema with imbrication had stomal leakage (p = 0.001). CONCLUSIONS: We reviewed the spectrum of stomal incontinence following Malone antegrade continence enema in 75 patients and developed a new grading scale to help standardize this complication. Imbrication provided stomal continence in all patients. Without imbrication almost 90% had no stomal incontinence or grade 1 leakage after long-term followup.

Epithelium-free bladder wall graft: epithelial ingrowth and regeneration--clinical implications for partial cystectomy.

PURPOSE: Most patients who need a bioengineered bladder wall have bladder cancer. A graft made with autologous urothelium would not be safe. To investigate the feasibility of providing bioengineered tissue for patients with partial cystectomy we evaluated the host and graft response after transplanting an epithelium-free graft. MATERIALS AND METHODS: De-epithelialized bladder wall grafts from male rats were transplanted on syngeneic female rat bladders after partial cystectomy. Urothelial morphology, vessel density, inflammation, stromal thickness and uroplakin expression were evaluated 1, 3, 6 and 9 months after surgery. Cell gender was distinguished by fluorescent in situ hybridization using unique X and Y chromosome probes. RESULTS: There was no significant graft contraction at any time. Male graft urothelial morphology and uroplakin expression were similar to those of controls at all time points. The donor bladder had decreased vessel density at early time points while the host had increased vascularity, which normalized in each by 6 months. Graft inflammation and edema normalized by 9 months. There was no muscular hypertrophy. Fluorescence in situ hybridization revealed early ingrowth of host female urothelium and a small fraction of male urothelial cells, which appeared between 1 and 3 months. CONCLUSIONS: Within 9 months de-epithelialized grafts appeared histologically as normal bladder, surprisingly faster than an equivalent model with full-thickness grafts. The safety and function of an epithelium-free graft must be determined in a large animal model. These early data in a small animal model substantiate the feasibility and equivalency of using grafts without epithelium, which would allow application in patients with cancer.

Autologous regeneration of blood vessels in urinary bladder matrices provides early perfusion after transplant to the bladder.

Large animal testing and clinical trials using bioengineered bladder for augmentation have revealed that large grafts fail due to insufficient blood supply. To address this critical issue, an in vivo staged implant strategy was developed and evaluated to create autologous, vascularized bioengineered bladder tissue with potential for clinical translation. Pig bladders were used to create acellular urinary bladder matrices (UBMs), which were implanted on the rectus abdominus muscles of rats and pigs to generate cellular and vascular grafts. Rectus-regenerated bladder grafts (rrBGs) were highly cellularized and contained an abundance of CD31-positive blood vessels, which were shown to be functional by perfusion studies. Muscle patterns within grafts showed increased smooth muscle formation over time and specifically within the detrusor compartment, with no evidence of striated muscle. Large, autologous rrBGs were transplanted to the pig bladder after partial cystectomy and compared to transplantation of control UBMs at 2 weeks and 3 months post-transplant. Functional, ink-perfused blood vessels were found in the central portion of all rrBGs at 2 weeks, while UBM grafts were significantly deteriorated, contracted and lacked central cellularization and vascularization. By 3 months, rrBGs had mature smooth muscle bundles and were morphologically similar to native bladder. This staged implantation technique allows for regeneration and harvest of large bladder grafts that are morphologically similar to native tissue with functional vessels capable of inosculating with host bladder vessels to provide quick perfusion to the central area of the large graft, thereby preventing early ischemia and contraction.

Combination product of dermal matrix, preconditioned human mesenchymal stem cells and timolol promotes wound healing in the porcine wound model.

A combination product of human mesenchymal stem/stromal cells (MSCs) embedded in an extracellular matrix scaffold and preconditioned with hypoxia and the beta-adrenergic receptor antagonist, timolol, combined with sustained timolol application post implantation, has shown promising results for improving wound healing in a diabetic mouse model. In the present study, we extend those findings to the more translatable large animal porcine wound model and show that the combined treatment promotes wound reepithelialization in these excisional wounds by 40.2% and increases the CD31 immunostaining marker of angiogenesis compared with the matrix control, while maintaining an accumulated timolol plasma concentration below the clinically safe level of 0.3 ng/mL after the 15-day course of topical application. Human GAPDH was not elevated in the day 15 wounds treated with MSC-containing device relative to wounds treated with matrix alone, indicating that the xenografted human MSCs in the treatment do not persist in these immune-competent animals after 15 days. The work demonstrates the efficacy and safety of the combined treatment for improving healing in the clinically relevant porcine wound model.