Practice patterns in classic bladder exstrophy: A global perspective.

INTRODUCTION: While evaluation and management options for classic bladder exstrophy (CBE) patients are numerous and varied, little is known regarding the relative utilization of these different methods throughout the world. A large group of exstrophy surgeons practicing globally was surveyed, seeking to document their methods of care. METHODS: A list of international exstrophy surgeons' email addresses was compiled using professional contacts and referral networking. An online survey was sent to each email address. Surgeons who had not performed a CBE closure within the previous 5 years were excluded. Survey questions queried the respondents' surgical practice type, years since training, and their preferred methods of preoperative evaluation, operative management, and postoperative management. Survey invitations were sent out starting in December 2014 and responses were collected for approximately 6 months. RESULTS: A total of 1152 valid email addresses were invited, resulting in 293 respondents (25%) from 39 countries and every American Urological Association (AUA) section. Seventy-six were excluded, leaving 217 respondents (Table). Respondents reported a median of 17 years since finishing their surgical training (IQR 8-25 years). Practice types included pediatric urology (n = 209), general urology (n = 9), pediatric surgery (n = 59), and other practice makeup (n = 3). On subgroup analyses, there were no significant regional practice differences, with the exception of complete primary repair of exstrophy (CPRE) and oral opioid prescribing being significantly higher in North America compared to other regions. DISCUSSION: Findings indicate that there may be diversity in CBE practice patterns globally. While most responding surgeons from regions outside of North America indicated modern staged repair of exstrophy (MSRE) as their preferred closure technique, a relatively equal distribution of respondents from North America selected CPRE and MSRE. A majority of North American surgeons chose performing osteotomies for both newborn and delayed closures, while an appreciable number of respondents from other regions selected never using osteotomies in their closures. Limitations to this study include a low survey response rate, particularly from surgeons outside of the United States, which may have significantly impacted the ability to draw meaningful global comparisons. CONCLUSIONS: Global variation among practices of surgeons performing CBE closures may exist. The wide range of methods demonstrated by this survey suggests the need for more conclusive comparative studies to elucidate whether an optimal standard exists. Local social factors, access to surgical expertise and transportation to referral centers, and finances play a role in what constitutes the best operative approach.

Patient-Reported Impact of Pelvic Organ Prolapse on Continence and Sexual Function in Women With Exstrophy-Epispadias Complex.

OBJECTIVE: This study aimed to characterize long-term urogynecologic issues of women with a history of bladder exstrophy and pelvic organ prolapse (POP) and to assess the impact of POP repair on continence and sexual function. DESIGN: Patient demographics and surgical history related to exstrophy and POP were collected through chart review. Patient perceptions regarding sexual function, urinary continence, and quality of life were assessed through Web-based administration of validated questionnaires: International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and POP-Urinary Incontinence Sexual Questionnaire. SETTING: Maryland, United States. PARTICIPANTS: Review of a single-institution exstrophy-epispadias complex database resulted in 25 adult female patients with a history of POP treated at the authors' institution. Eleven patients participated and were included in the analysis. MAIN OUTCOME MEASURES: Urinary continence and sexual function. RESULTS: All participants underwent surgical repair for prolapse, with 7 (63.6%) experiencing unsuccessful initial repair and subsequent recurrence. Median total number of POP repairs was 2.5 (1-4). After correction of POP, patients reported a median improvement in International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form scores of 11 (21 to -1) of 21 and in POP-Urinary Incontinence Sexual Questionnaire scores of 9.5 (6.5-33.0) of 48.0. With regard to urinary continence, 6 (54.5%) patients presently reported no incontinence, 3 (27.3%) reported mild incontinence, and 2 (18.2%) reported continuous incontinence. CONCLUSIONS: Pelvic organ prolapse poses significant reductions in quality of life for women born with exstrophy, with effects on urinary continence and sexual function. Identification and correction of prolapse seems to result in notable improvements in the lives of these patients.

Sexual Function and Quality of Life Before and After Penile Prosthesis Implantation Following Radial Forearm Flap Phalloplasty.

OBJECTIVE: To provide sexual function and quality of life outcomes in patients with severe penile deficiency who underwent radial forearm flap phalloplasty with and without penile prosthesis implantation. PATIENTS AND METHODS: Patients with history of severe penile deficiency who underwent microsurgical radial forearm flap phalloplasty with and without penile prosthesis implantation between 2007 and 2014 were identified. They completed a set of web-based validated questionnaires including the International Index of Erectile Function, the Pediatric Penile Perception Score, the Sexual Quality of Life for Men, and several items addressing general quality of life. Outcomes were compared between groups. RESULTS: Nine of the 12 identified patients who had prosthesis after phalloplasty and 4 out of the 7 phalloplasty-only patients completed the survey, resulting in an overall response rate of 68%. Among the phalloplasty-prosthesis patients, 66% reported current sexual activity and 78% reported regular masturbation, whereas 1 of the 4 phalloplasty-only patients reported both. Prosthesis patients scored notably higher in all domains of the International Index of Erectile Function except for sexual desire. In contrast, they demonstrated similar scores of penile perception, as well as general and sexual quality of life. CONCLUSION: Among patients who have undergone flap phalloplasty, the subsequent placement of penile prosthesis appears to effectively allow for both intercourse and masturbation, resulting in measurable improvements in orgasmic function, intercourse satisfaction, and overall sexual satisfaction. Despite these important benefits, prosthesis placement does not appear to result in improvements in penile perception scores, or general or sexual quality of life.

Profound Hematuria in a Toddler Yields an Unusual Diagnosis.

Herein we present a rare case of profound recurrent gross hematuria in a young child with no known predisposing event. She was eventually diagnosed with a large lymphovascular malformation of the bladder. She underwent multiple unsuccessful attempts at embolization before eventual curative partial cystectomy.

Continence in the cloacal exstrophy patient: What does it cost?

BACKGROUND: Surgical advancements have made cloacal exstrophy (CE) a survivable condition, though management remains complex. Urologic, orthopedic, colorectal and gynecologic interventions are not standardized, and the cost of this care is high. While the importance of a successful primary closure in terms of outcomes is known, the economic consequences of failure remain uncharacterized. METHODS: A prospectively maintained institutional database of epispadias-exstrophy complex patients was reviewed for continent CE patients. Hospital charges for all inpatient admissions prior to achieving urinary continence were inflation-adjusted to year 2013 values using Consumer Price Index for medical care published by the United States Bureau of Labor Statistics. Records for which charge data were incomplete were completed by using single mean imputation, also inflation-adjusted. Descriptive data are presented as mean±standard deviation (SD). RESULTS: Of 102 CE patients, 35 had available hospital charge data: 15 who underwent successful primary closure at the authors' institution and 20 who presented after previously failed primary closures at referring institutions. The mean±SD hospital charges for primary closure in the success group were $136,201±$48,920. These patients then underwent subsequent additional surgeries that accrued charges of $59,549±$25,189 in order to achieve continence. Overall, successful primary closures accumulated hospital charges of $200,366±$40,071. In comparison, patients referred after prior failure required significantly more hospital admissions and additional charges of $207,674±$65,820 were required to achieve continence (p<0.001). Patients who failed primary closure are estimated to accumulate 70% more total health care charges compared to the group following successful primary closure. CONCLUSION: The cost of CE management until urinary continence is high, averaging more than $200,000 in inpatient hospital charges alone. Initial success is desirable from both an outcomes and economic perspective, as the cost of salvaging a failed primary closure at our institution is similar to the overall costs of a successful closure; this is in addition to the cost of any previous failed closures. Further studies will be required to determine the optimal timing of surgical management in terms of both patient outcomes and financial consequences.

Newborn exstrophy closure without osteotomy: Is there a role?

INTRODUCTION: Recent articles document successful classic bladder exstrophy (CBE) closure without osteotomy. Still, many patients require osteotomy if they have a large bladder template and pubic diastasis, or non-malleable pelvis. OBJECTIVE: To understand the indications and outcomes of bladder closure with and without pelvic osteotomy in patients younger than 1 month of age. METHODS: An institutional database of 1217 exstrophy-epispadias patients was reviewed for CBE patients closed at the authors' institution within the first month of life. Patient demographics, closure history, pubic diastasis distance, bladder capacity, and outcomes were recorded and compared using chi-square tests between osteotomy and non-osteotomy patients. Failure was defined as bladder dehiscence, prolapse, vesicocutaneous fistula, or bladder outlet obstruction requiring reoperation. Bladder capacity >100 mL was deemed sufficient for bladder neck reconstruction (BNR). RESULTS: One hundred CBE patients were included for analysis: 38 closed with osteotomy (26 male, 12 female), and 62 closed without osteotomy (42 male, 20 female). There were four failed closures in the osteotomy group (2 dehiscence, 2 prolapse) and four failed closures in the non-osteotomy group (2 dehiscence, 2 prolapse). This corresponded to statistically equivalent rates of failure between the osteotomy and non-osteotomy groups (10.5% vs. 6.5%, p = 0.466). There was no statistically significant difference between the groups' ability to achieve bladder capacity sufficient for BNR (82% vs. 71%, p = 0.234). DISCUSSION: A successful primary bladder closure, regardless of the use of osteotomy, has been shown to be the single most important predictor of eventual continence. Because of the complexity of exstrophy manifestations, a multidisciplinary team approach is of the utmost importance. Based on our institutional experience, closure without osteotomy is considered when patients are <72 h of life, have a pubic diastasis <4 cm, malleable pelvis, and pubic apposition without difficulty. Rates of successful closure and attaining sufficient capacity for BNR were both statistically equivalent across groups. This retrospective study is limited by selection bias and the significant difference in follow-up time between groups. Nevertheless, as a high-volume exstrophy center this study draws from one of the largest cohorts available. CONCLUSIONS: Regardless of the type of closure undertaken, there clearly is a role for newborn CBE closure without pelvic osteotomy in patients considered suitable for closure by both the pediatric urologist and orthopedic consultant. However, if there is any doubt concerning pubic diastasis width, pelvic malleability, or ease of pubic apposition, an osteotomy is highly recommended.

Pediatric and adolescent renal cell carcinoma.

OBJECTIVE: Renal cell carcinoma (RCC) is an uncommon malignancy among children and adolescents. Because of this, there has been relatively sparse research and evidence on the topic. As the body of research regarding pediatric and adolescent RCC has developed in recent years, it has become increasingly clear that it demonstrates important differences from the much more common adult-type RCC. This review aims to examine and summarize the current literature, with a focus on the ways that pediatric and adolescent RCC differ from the adult disease, and to make recommendations for evaluation and management based on this evidence whenever possible. METHODS AND MATERIALS: A thorough search of all articles relating to pediatric and adolescent RCC has been undertaken using PubMed. The reference lists from all relevant articles have been further reviewed, to ensure inclusion of all pertinent literature. CONCLUSION: The most significant development in recent years has been the realization that most of the pediatric and adolescent RCC cases, but only a very small fraction of adult RCC cases, demonstrate "translocation tumor" pathology. It is likely that such differences may eventually explain many of the previous observations regarding differences in behavior of RCC among children and teenagers. At this point, however, the relevance of translocation pathology to clinical management remains unclear, and so most continue to treat these patients in much the same way as those with the more conventional tumor subtypes.

Secondary reclosure in classic bladder exstrophy: challenges and outcomes.

OBJECTIVE: To analyze the outcomes of failed classic bladder exstrophy (CBE) reclosure with and without pelvic osteotomy. Each failed CBE closure decreases the chance of eventual continence. To minimize secondary failures, most institutions use pelvic osteotomy with reclosure. Reclosure with and without osteotomy can still fail. METHODS: An institutional database of 1210 exstrophy-epispadias complex patients was reviewed for CBE patients who had 2 prior failed closures with the third closure at the authors' institution. Patient demographics, closure history, diastasis distance, bladder capacity, and outcomes were examined by chi-square tests comparing osteotomy status with first reclosure. RESULTS: Of 848 CBE patients, 17 met inclusion criteria: 12 with osteotomy at reclosure (group 1) and 5 without (group 2). Median time between initial closure and reclosure in the 2 groups were 6.5 months (range, 0-42 months) and 3 months (range, 0-59 months), respectively. There was no significant difference in the rate of attaining sufficient bladder capacity for bladder neck reconstruction (BNR; 100 cc) between groups 1 and 2 (42% vs 40%; P = .490). Within group 1, patients receiving proper immobilization with external fixation (n = 5) demonstrated a significantly greater rate of attaining sufficient bladder capacity for BNR compared with patients who did not (80% vs 14%; P = .023). There were no differences in the rates of attaining dryness per urethra. CONCLUSION: CBE outcomes worsen with each successive failed closure. Reclosure should be performed with osteotomy and proper immobilization to maximize the chance of sufficient capacity for BNR or augmentation cystoplasty.

Modern management of the exstrophy-epispadias complex.

The exstrophy-epispadias complex is a rare spectrum of malformations affecting the genitourinary system, anterior abdominal wall, and pelvis. Historically, surgical outcomes were poor in patients with classic bladder exstrophy and cloacal exstrophy, the two more severe presentations. However, modern techniques to repair epispadias, classic bladder exstrophy, and cloacal exstrophy have increased the success of achieving urinary continence, satisfactory cosmesis, and quality of life. Unfortunately, these procedures are not without their own complications. This review provides readers with an overview of the management of the exstrophy-epispadias complex and potential surgical complications.

Safety and efficacy of staged pelvic osteotomies in the modern treatment of cloacal exstrophy.

INTRODUCTION AND OBJECTIVE: Staged pelvic osteotomy (SPO) prior to bladder closure has been shown to be a safe and effective method for achieving pubic approximation in cloacal exstrophy (CE) patients with extreme diastasis. However, SPO outcomes have never been compared to those for combined pelvic osteotomy (CPO) at the time of closure in CE patients. METHODS: A prospectively maintained database of 1208 exstrophy-epispadias complex patients was reviewed for CE patients treated with pelvic osteotomies. Inclusion criteria were osteotomy at the authors' institution and closure within two months of osteotomy. After inclusion, patients were separated into four groups depending on osteotomy procedure (SPO vs. CPO) and whether their osteotomy occurred with primary closure or re-closure. Patient demographics, closure history, pre-operative diastasis measurement, most recent post-operative diastasis measurement, and outcomes were recorded and compared by chi-squared tests and ANOVA. RESULTS: Among 116 CE patients reviewed, 46 met inclusion criteria. With primary closure or re-closure, 27 had SPO and 19 had CPO. No SPO re-closure patients had previous osteotomy; 4 CPO re-closure patients had a previous osteotomy with closure. Median time between osteotomy and closure in SPO patients was 14 days. Median follow-up after SPO and CPO were 4 and 11 years, respectively. SPO significantly reduced the pre-operative diastasis compared to CPO on most recent diastasis measurement (3.5 cm vs. 0.4 cm, p=0.003). There were no significant differences in the overall complication rate, or the rates of each specific complication, between the SPO and CPO groups. No patients had wound dehiscence or prolapse. One CPO patient was able to intermittently catheterize per urethra while all other patients required continent urinary diversion to achieve continence. CONCLUSIONS: To the authors' knowledge, this is the first study comparing SPO and CPO outcomes in CE patients. SPO reduces pre-operative diastasis more than CPO, and does not appear to incur increased rates of complication, closure failure, or incontinence. Due to its apparent safety and greater efficacy, SPO should be considered in all CE patients with extreme diastases undergoing primary closure or re-closure.

C-X-C chemokine receptor 7: a functionally associated molecular marker for bladder cancer.

BACKGROUND: C-X-C chemokine receptor 4 (CXCR4) and CXCR7 are 7-transmembrane chemokine receptors of the stroma-derived factor (SDF-1). CXCR4, but not CXCR7, has been examined in bladder cancer (BCa). This study examined the functional and clinical significance of CXCR7 in BCa. METHODS: CXCR4 and CXCR7 levels were measured in BCa cell lines, tissues (normal = 25; BCa = 44), and urine specimens (n = 186) by quantitative polymerase chain reaction and/or immunohistochemistry. CXCR7 function in BCa cells were examined by transient transfections using a CXCR7 expression vector or small interfering RNA. RESULTS: In BCa cell lines, CXCR7 messenger RNA levels were 5- to 37-fold higher than those for CXCR4. Transient overexpression of CXCR7 in BCa cell lines promoted growth and chemotactic motility. CXCR7 colocalized and formed a functional complex with epidermal growth factor receptor, phosphoinositide 3-kinase/Akt, Erk, and src and induced their phosphorylation. CXCR7 also induced up-regulation of cyclin-D1 and bcl-2. Suppression of CXCR7 expression reversed these effects and induced apoptosis. CXCR7 messenger RNA levels and CXCR7 staining scores were significantly (5- to 10-fold) higher in BCa tissues than in normal tissues (P < .001). CXCR7 expression independently associated with metastasis (P = .019) and disease-specific mortality (P = .03). CXCR7 was highly expressed in endothelial cells in high-grade BCa tissues when compared to low-grade BCa and normal bladder. CXCR7 levels were elevated in exfoliated urothelial cells from high-grade BCa patients (P = .0001; 90% sensitivity; 75% specificity); CXCR4 levels were unaltered. CONCLUSIONS: CXCR7 promotes BCa cell proliferation and motility plausibly through epidermal growth factor receptor receptor and Akt signaling. CXCR7 expression is elevated in BCa tissues and exfoliated cells and is associated with high-grade and metastasis.

Comparison of safety, renal function outcomes and efficacy of laparoscopic and percutaneous radio frequency ablation of renal masses.

PURPOSE: With the increased incidence of low stage renal cancers, thermal ablation technology has emerged as a viable treatment option. Current AUA (American Urological Association) guidelines include thermal ablation as a treatment modality for select individuals. We compared the laparoscopic and percutaneous approach for the radio frequency ablation of renal tumors under the guidance of urological surgeons. MATERIALS AND METHODS: We reviewed our radio frequency ablation database of patients with renal masses undergoing laparoscopic or computerized tomography guided percutaneous radio frequency ablation with simultaneous peripheral fiberoptic thermometry from November 2001 to January 2011 at a single tertiary care center. Data were collected on patient demographics, and surgical and clinicopathological outcomes stratified by approach. RESULTS: A total of 298 patients with 316 renal tumors underwent laparoscopic (122 tumors) or computerized tomography guided (194 tumors) radio frequency ablation. There were no statistically significant differences between the laparoscopic and computerized tomography guided radio frequency ablation groups with respect to patient demographics, complication rates and renal functional outcomes (p>0.05). The 3-year Kaplan-Meier estimation of radiographic recurrence-free probability was 95% for computerized tomography guided radio frequency ablation and 94% for laparoscopic radio frequency ablation (p=0.84). Subanalysis of the 212 (67%) renal cell carcinoma tumors showed a 3-year Kaplan-Meier estimation of oncologic recurrence-free probability (post-ablation biopsy proven viable tumor) of 94% for computerized tomography guided radio frequency ablation and 100% for laparoscopic radio frequency ablation (p=0.16). Median followup was 21 months for laparoscopic radio frequency ablation) and 19 months for computerized tomography guided radio frequency ablation. CONCLUSIONS: Laparoscopic and computerized tomography guided radio frequency ablation appear safe and effective with statistically equivalent rates of complications and recurrence.

Chemokine and chemokine receptor expression in kidney tumors: molecular profiling of histological subtypes and association with metastasis.

PURPOSE: Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms. We evaluated the expression of these chemokines and chemokine receptors in kidney specimens. MATERIALS AND METHODS: Using quantitative polymerase chain reaction we measured mRNA levels of IL-8, CXCR4 and 7, and SDF1 isoforms α, ß and γ in a total of 166 specimens from 86 patients, including 86 tumor samples and 80 matched normal kidney samples. Mean ± SD followup was 18.9 ± 12 months (median 19.5). Renal cell carcinoma specimens included the clear cell, papillary and chromophobe subtype in 65, 10 and 5 cases, respectively, and oncocytoma in 6. A total of 17 cases were positive for metastasis. RESULTS: Median CXCR4 and 7, and SFD1-γ levels were increased twofold to tenfold. SDF1-α and ß were unchanged or lower in clear cell renal cell carcinoma and papillary tumors than in normal tissue. Median SDF1-γ, IL-8, and CXCR4 and 7 were increased threefold to fortyfold in chromophobe tumors compared to oncocytoma. CXCR4 and 7 were increased in tumors less than 4 cm (mean 3,057 ± 2,230 and 806 ± 691) compared to oncocytoma (336 ± 325 and 201 ± 281, respectively, p ≤0.016). On multivariate analysis CXCR4 (p = 0.01), CXCR7 (p = 0.02) and SDF1-ß (p = 0.005) were independently associated with metastasis. Combined CXCR7 plus SDF1-α and CXCR7 plus IL-8 markers showed the highest sensitivity (71% to 81%) and specificity (75% to 80%) of all individual or combined markers. CONCLUSIONS: Chemokines and chemokine receptors differentiate renal cell carcinoma and oncocytoma. Combined SDF1-α plus CXCR7 and IL-8 plus CXCR7 markers have about 80% accuracy for predicting renal cell carcinoma metastasis.