Long-term outcomes and patterns of relapse in patients with bilateral Wilms tumor or bilaterally predisposed unilateral Wilms tumor, a report from the COG AREN0534 study.

The objective of this study is to report the long-term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event-free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre-specified groups. Two hundred and twenty-two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8-year EFS was 75% (95% confidence interval: 69%-83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow-up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post-chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.

Prognostic impact of lymph node involvement and loss of heterozygosity of 1p or 16q in stage III favorable histology Wilms tumor: A report from Children's Oncology Group Studies AREN03B2 and AREN0532.

INTRODUCTION: The prognostic impact of positive lymph nodes (LN+) and/or singular loss of heterozygosity (LOH) of 1p or 16q were assessed in children with stage III favorable histology Wilms tumor (FHWT) enrolled on AREN0532 or AREN03B2 alone. PATIENTS AND METHODS: A total of 635 stage III FHWT vincristine/dactinomycin/doxorubicin (DD4A)-treated patients met inclusion criteria. Event-free survival (EFS) and overall survival are reported overall and by LN sampling, LN status, LOH 1p, LOH 16q, and a combination of LN status and singular LOH. Patients with unknown or positive combined LOH of 1p and 16q status and AREN03B2-only patients with unknown outcomes or treatment other than DD4A were excluded. RESULTS: EFS did not differ by study, supporting pooling. Lack of LN sampling (hazard ratio [HR], 2.12; p = .0037), LN positivity (HR, 2.78; p = .0002), LOH 1p (HR, 2.18; p = .0067), and LOH 16q (HR, 1.72; p = .042) were associated with worse EFS. Compared with patients with both LN- and LOH-, those with negative nodes but positive LOH 1p or 16q and those with LN+ but LOH- for 1p or 16q had significantly worse EFS (HR, 3.05 and 3.57, respectively). Patients positive for both LN and LOH had the worst EFS (HR, 6.33; overall group factor, p < .0001). CONCLUSION: Findings confirm LN+ status as an adverse prognostic factor amplified by presence of singular LOH 1p or 16q, supporting study of intensified therapy for patients with LN+ in combination with singular LOH in a prospective clinical trial.

Management and Outcomes of Wilms Tumor With Suprarenal Intravascular Extension: A Pediatric Surgical Oncology Research Collaborative Study.

OBJECTIVE: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. BACKGROUND: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. METHODS: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. RESULTS: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P =0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P =0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P =0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. CONCLUSIONS: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.

Current surgical approaches to pediatric renal tumors.

Pediatric renal tumors are among the most common pediatric solid malignancies. Surgical resection is a key component in the multidisciplinary therapy for children with kidney tumors. Therefore, it is imperative that surgeons caring for children with renal tumors fully understand the current standards of care in order to provide appropriate surgical expertise within this multimodal framework. Fortunately, the last 60 years of international, multidisciplinary pediatric cancer cooperative group studies have enabled high rates of cure for these patients. This review will highlight the international surgical approaches to pediatric patients with kidney cancer to help surgeons understand the key differences and similarities between the European (International Society of Pediatric Oncology) and North American (Children's Oncology Group) recommendations.

Bilateral Wilms tumor with anaplasia: A report from the Children's Oncology Group Study AREN0534.

INTRODUCTION: The purpose of this study is to examine the outcomes in children with anaplastic bilateral Wilms tumor (BWT) from study AREN0534 in order to define potential prognostic factors and areas to target in future clinical trials. METHODS: Demographic and clinical data from AREN0534 study patients with anaplasia (focal anaplasia [FA], or diffuse anaplasia [DA]) were compared. Event-free survival (EFS) and overall survival (OS) were reported using Kaplan-Meier estimation with 95% confidence bands, and differences in outcomes between FA and DA compared using log-rank tests. The impact of margin status was analyzed. RESULTS: Twenty-seven children who enrolled on AREN0534 had evidence of anaplasia (17 DA, 10 FA) in at least one kidney and were included in this analysis. Twenty-six (96%) had BWT. Nineteen percent had anaplastic histology in both kidneys (four of 17 DA, and one of 10 FA). Forty-six percent with BWT had bilateral nephron-sparing surgery (NSS); one child who went off protocol therapy, eventually required bilateral completion nephrectomies. Median follow-up for EFS and OS was 8.6 and 8.7 years from enrollment. Four- and 8-year EFS was 53% [95% confidence interval (CI): 34%-83%] for DA; 4-year EFS was 80% [95% CI: 59%-100%], and 8-year EFS 70% [95% CI: 47%-100%] for FA. Three out of 10 children with FA and eight out of 17 children with DA had events. EFS did not differ statistically by margin status (p = .79; HR = 0.88). Among the six children who died (five DA, one FA), all experienced prior relapse or progression within 18 months. CONCLUSION: Events in children with DA/FA in the setting of BWT occurred early. Caution should be taken about interpreting the impact of margin status outcomes in the context of contemporary multimodal therapy. Future targeted investigations in children with BWT and DA/FA are needed.

Treatment and Outcomes of Congenital Ovarian Cysts A Study by the Canadian Consortium for Research in Pediatric Surgery (CanCORPS).

OBJECTIVE: We conducted a multicenter study to assess treatments and outcomes in a national cohort of infants with congenital ovarian cysts. SUMMARY BACKGROUND DATA: Wide variability exists in the treatment of congenital ovarian cysts. The effects of various treatment strategies on outcomes, specifically ovarian preservation, are not known. METHODS: Female infants diagnosed with congenital intra-abdominal cysts between 2013 and 2017 at 10 Canadian pediatric surgical centers were retrospectively evaluated. Sonographic characteristics, median time to cyst resolution, incidence of ovarian preservation, and predictors of surgery were evaluated. Subgroup analyses were performed in patients with complex cysts and cysts ≥40 mm in diameter. RESULTS: The study population included 189 neonates. Median gestational age at diagnosis and median maximal prenatal cyst diameter were 33 weeks and 40 mm, respectively. Cysts resolved spontaneously in 117 patients (62%), 14 (7%) prenatally, and the remainder at a median age of 124 days. Intervention occurred in 61 patients (32%), including prenatal aspiration (2, 3%), ovary sparing resection (14, 23%), or oophorectomy (45, 74%). Surgery occurred at a median age of 7.4weeks. Independent predictors of surgery included postnatal cyst diameter ≥40 mm [odds ratio (OR) 6.19, 95% confidence interval (CI) 1.66-35.9] and sonographic complex cyst character (OR 63.6, 95% CI 10.9-1232). There was no significant difference in the odds of ovarian preservation (OR 3.06, 95% CI 0.86 -13.2) between patients who underwent early surgery (n = 22) and those initially observed for at least 3 months (n = 131). CONCLUSIONS: Most congenital ovarian cysts are asymptomatic and spontaneously resolve. Early surgical intervention does not increase ovarian preservation.

Survival effect of complete surgical resection of the primary tumor in patients with metastatic, high-risk neuroblastoma in a large Canadian cohort.

PURPOSE: To determine whether extent of surgical resection of the primary tumor correlates with survival in patients with International Neuroblastoma Staging System (INSS) stage 4, high-risk neuroblastoma. METHODS: Data were extracted for patients with newly diagnosed INSS stage 4, high-risk neuroblastoma between 2001 and 2019 from the national Cancer in Young People in Canada (CYPC) database. Complete resection was defined as gross total resection of primary tumor based on operative reports. Primary endpoints were 3 and 5-year event-free (EFS) and overall survival (OS). Survival analyses were completed using log-rank test and Cox proportional hazards regression including covariates of age, sex, decade of treatment (2001-2009 vs. 2010-2019), immunotherapy, and tandem stem cell transplant (SCT). RESULTS: One-hundred and forty patients with complete surgical data were included. On univariate analysis, 3-year EFS and OS for patients that had complete versus incomplete resection was 71% (95% CI 57-80%) vs. 48% (36-60%) and 86% (75-93%) vs. 64% (51-74%), p = .008 and p = .002, respectively. 5-year EFS and OS for patients with complete resection also demonstrated significantly improved survival. On Cox Proportional Hazards models adjusted for age, immunotherapy, tandem SCT, and surgical resection, only complete resection was associated with statistically significant improved 3 year EFS and OS, HR = 0.48 (0.29-0.81; p = .006) and HR = 0.42 (0.24-0.73; p = .002). CONCLUSIONS: In a large Canadian INSS stage 4 high-risk neuroblastoma cohort, complete surgical resection was associated with increased EFS and OS. Within the constraints of a retrospective study, these results suggest that the ability to achieve primary tumor complete resection in patients with metastatic high-risk disease is associated with improved survival.

Technical advances in the surgical management of Wilms tumors in children.

Surgery is one of the cornerstones of Wilms tumor treatment. In this article, we present technical advancements that are finding their way into the armamentarium of pediatric cancer surgeons. We discuss the current approaches, challenges, opportunities, and future directions of minimally invasive surgery (laparoscopic and robotics), image-guided surgery, and fluorescence-guided surgery. Furthermore, we discuss the use of intraoperative ultrasonography, as well as the use of new techniques to improve the quality of lymph node sampling.

Development and implementation of a postgraduate medical education-wide initiative in quality improvement and patient safety.

BACKGROUND: Quality improvement and patient safety (QIPS) have been assigned a higher profile in CanMEDS 2015, CanMEDS-Family Medicine 2017 and new accreditation standards, prompting an initiative at Dalhousie University to create a vision for integrating QIPS into postgraduate medical education. OBJECTIVE: The purpose of this study is to describe the implementation of a QIPS strategy across residency education at Dalhousie University. METHODS: A QIPS task force was formed, and a literature review and needs assessment survey were completed. A needs assessment survey was distributed to all Dalhousie residency programme directors. 12 programme directors were interviewed individually to collect additional feedback. The results were used to develop a 'road map' of recommendations with a graduated timeline. RESULTS: A task force report was released in February 2018. 46 recommendations were developed with a timeframe and responsible party identified for each. Implementation of the QIPS strategy is underway, and evaluation and challenges faced will be described. CONCLUSIONS: We have developed a multiyear strategy that is available to provide guidance and support to all programmes in QIPS. The development and implementation of this QIPS framework may serve as a template for other institutions who seek to integrate these competencies into residency training.

MR Imaging of Pediatric Neuroblastoma: Is Gadolinium Enhancement Necessary for Evaluation of Image-Defined-Risk Factors?

Background: Pre-treatment stratification and outcomes of neuroblastoma patients often depend on the assessment of image-defined risk factors (IDRFs) on MR Imaging, usually using Gadolinium-contrast materials which are cautioned in pediatrics. We aimed to address whether gadolinium contrast-enhanced sequences are necessary to identify the presence/absence of IDRFs. Methods: Patients with neuroblastoma with MR imaging were retrospectively identified from 2005 to 2021. Ninety confirmed IDRFs were evaluated in 23 patients. Corresponding MR studies were anonymized, randomized, and independently evaluated by 3 fellowship-trained pediatric radiologists. Each radiologist assessed the studies twice. At the first reading, all enhanced sequences were omitted, while in the second reading, the full study with enhanced sequences were included. Consensus reading was obtained among readers. Inter- and intra-rater agreements using Kappa statistics (κ) as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of non-enhanced MR in assessing IDRFs with respect to enhanced MR were calculated. Results: There were substantial (ĸ: 0.64-0.73) intra-reader agreements, and moderate to substantial (ĸ: 0.57-0.62) inter-reader agreements among radiologists in identifying IDRFs using non-enhanced MR. Non-enhanced MR had a sensitivity of 87.8% (95% CI [79-94]), specificity of 93% (89-96), PPV of 82.3 (73-89), NPV of 95.4 (92-98), and accuracy of 91.6 (88-94) in identifying IDRFs. However, 5/23 patients (21.7%) had a change in staging with the inclusion of contrast sequences. Conclusion: Although contrast sequences have a role in IDRF assessment, the majority can be adequately assessed on MR without gadolinium-contrast enhancement. Validation in a larger cohort is an important next step.

White paper: Oncofertility in pediatric patients with Wilms tumor.

The survival of childhood Wilms tumor is currently around 90%, with many survivors reaching reproductive age. Chemotherapy and radiotherapy are established risk factors for gonadal damage and are used in both COG and SIOP Wilms tumor treatment protocols. The risk of infertility in Wilms tumor patients is low but increases with intensification of treatment including the use of alkylating agents, whole abdominal radiation or radiotherapy to the pelvis. Both COG and SIOP protocols aim to limit the use of gonadotoxic treatment, but unfortunately this cannot be avoided in all patients. Infertility is considered one of the most important late effects of childhood cancer treatment by patients and their families. Thus, timely discussion of gonadal damage risk and fertility preservation options is important. Additionally, irrespective of the choice for preservation, consultation with a fertility preservation (FP) team is associated with decreased patient and family regret and better quality of life. Current guidelines recommend early discussion of the impact of therapy on potential fertility. Since most patients with Wilms tumors are prepubertal, potential FP methods for this group are still considered experimental. There are no proven methods for FP for prepubertal males (testicular biopsy for cryopreservation is experimental), and there is just a single option for prepubertal females (ovarian tissue cryopreservation), posing both technical and ethical challenges. Identification of genetic markers of susceptibility to gonadotoxic therapy may help to stratify patient risk of gonadal damage and identify patients most likely to benefit from FP methods.

Inflammatory myofibroblastic tumor: A multi-institutional study from the Pediatric Surgical Oncology Research Collaborative.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi-institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty-two patients were identified with median age of 11 years. Thirty-three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety-one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty-six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow-up time was 36 months. Overall 5-year survival was 95% and 5-year event-free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.

Incidence and management of pleural effusions in patients with Wilms tumor: A Pediatric Surgical Oncology Research Collaborative study.

Wilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi-institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P < .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event-free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage-specific treatment regimens.

Where to start? Injury prevention priority scores for traumatic injuries in Canada.

BACKGROUND: Given limited resources for injury prevention, it is essential to determine which mechanisms of injury to target to provide the most benefit to the largest proportion of the population. We developed objective, evidence-based injury prevention priority scores (IPPSs) for the Canadian population across 4 prevention perspectives: mortality, injury severity, resource use and societal cost. METHODS: We performed a retrospective cohort study of all injuries in Canada from 2009/10 to 2013/14. Hospital admissions were obtained from the Discharge Abstract Database, and deaths from the Statistics Canada Canadian Vital Statistics Death Database. For each mechanism of injury, we calculated an IPPS as a balanced measure of injury frequency and 1) mortality rate, 2) median 1 - ICISS (Injury Severity Score derived from the International Statistical Classification of Diseases and Related Health Problems, 10th revision, enhanced Canadian version), 3) median cost per hospital stay or 4) median potential years of life lost (PYLL), providing a ranking of mechanisms of injury in priority order. The IPPS by definition has a mean of 50 and a standard deviation of 10. The higher the IPPS, the higher the priority for injury prevention. RESULTS: A total of 694 535 injuries were identified over the study period. The most frequent mechanism of injury was falls (391 068 [56.3%]). The overall mortality rate was 0.09 deaths/injured person, the median 1 - ICISS was 0.017, the median cost was $5217, and the median PYLL was 0. The mechanisms with the 3 highest IPPSs were falls (75), self-harm (67) and drowning (66) for mortality; falls (77), drowning (70) and suffocation (61) for severity; falls (80), suffocation (63) and fire (60) for resource use; and falls (72), assault (62), and firearms and legal interventions (59 in both cases) for societal cost. CONCLUSION: This study produced IPPSs for traumatic injuries in Canada that provide objective and quantifiable methods for identifying mechanisms of injury to target for specific prevention initiatives. Preventing falls would provide the most benefit to the largest proportion of Canadians and should be prioritized in injury-prevention policy.

Clinically and biologically relevant subgroups of Wilms tumour defined by genomic and epigenomic analyses.

BACKGROUND: Although cure rates for Wilms tumours (WT) are high, many patients receive therapy with attendant long-term complications. Our goal was to stratify WT using genome-wide analyses to identify candidate molecular features for patients who would benefit from a reduction in therapy. METHODS: We generated DNA methylation and exome sequencing data on WT-kidney pairs (n = 57) and unpaired tumours (n = 27) collected either at our centre or by the Children's Oncology Group. Samples were divided into a discovery set (n = 32) and validation set (n = 52). RESULTS: Analysis of DNA methylation revealed two subgroups of WT with distinct features. Subgroup A has a similar DNA methylation profile to mature kidney, while Subgroup B has genome-wide dysregulation of DNA methylation. The rate of non-synonymous missense mutations and segmental chromosomal aberrations was higher in Subgroup B tumours, suggesting that this group has genome instability related to its epigenetic state. Subgroup A had a higher proportion of cases of bilateral disease. Tumours with high-risk histology or from patients who relapsed were only found in Subgroup B. CONCLUSION: We have identified subgroup-specific molecular events that could inform future work supporting more targeted therapeutic approaches and patient stratification. We propose a novel developmental tumour model based on these findings.

Clinical Outcomes of the Upper Urinary Tract after Ureteral Clipping for Treatment of Low Functioning or Nonfunctioning Renal Moieties.

PURPOSE: A growing body of evidence suggests that it is safe to ligate the ureter of poorly functioning renal moieties during renal transplantation. We present clinical outcomes and data on hydronephrosis progression in pediatric cases associated with ectopic ureters and obstructive ureteroceles. MATERIALS AND METHODS: We prospectively collected data for 35 consecutive patients (23 females and 12 males) who underwent ureteral clipping between February 2011 and August 2016. Patients were divided into 4 groups consisting of 1) duplex system with ectopic ureter (45.7%), 2) duplex system with a large ureterocele (11.4%), 3) other duplex system (8.6%) and 4) single system kidneys (34.3%). Patients were followed for clinical outcomes and hydronephrosis trends. Comparisons included preoperative and postoperative anteroposterior diameter, maximal ureteral diameter and ureterocele size. RESULTS: Median age at surgery was 59 months (IQR 11 to 120, range 5 to 216). Median ± SD operative time was 108.9 ± 31.1 minutes (range 20 to 180) and median length of stay was 7.5 hours (IQR 6 to 19, range 5 to 336). Immediate resolution of urinary incontinence was observed in all 16 ectopic ureter cases. After a median ± SD followup of 20.8 ± 13.8 months (IQR 8.5 to 30, range 6 to 50) 97.2% of the patients remained asymptomatic. No significant differences were observed between initial and last anteroposterior diameter measurements except in group 1 (p = 0.001). All ureteroceles demonstrated a significant decrease in median ± SD size after clipping (from 2.7 ± 0.41 to 0.53 ± 0.92 cm, p = 0.003). Pyonephrosis developed in 1 patient, who underwent laparoscopic nephrectomy. CONCLUSIONS: Ureteral clipping appears to be a reasonable, safe and effective option for pediatric patients in the reported settings, with the potential to be simpler and quicker than extirpative or reconstructive procedures.

The transition of young adults with lifelong urological needs from pediatric to adult services: An international children's continence society position statement.

INTRODUCTION: Children with urinary tract disorders managed by teams, or individual pediatricians, urologists, nephrologists, gastroenterologists, neurologists, psychologists, and nurses at some point move from child-centered to adult-centered health systems. The actual physical change is referred to as the transfer whilst the process preceding this move constitutes transition of care. Our aims are twofold: to identify management and health-service problems related to children with congenital or acquired urological conditions who advance into adulthood and the clinical implications this has for long-term health and specialist care; and, to understand the issues facing both pediatric and adult-care clinicians and to develop a systems-approach model that meets the needs of young adults, their families and the clinicians working within adult services. METHODS: Information was gleaned from presentations at an International Children's Continence Society meeting with collaboration from the International Continence Society, that discussed problems of transfer and transitioning such children. Several specialists attending this conference finalized this document identifying issues and highlighting ways to ease this transition and transfer of care for both patients and practitioners. RESULTS: The consensus was, urological patients with congenital or other lifelong care needs, are now entering adulthood in larger numbers than previously, necessitating new planning processes for tailored transfer of management. Adult teams must become familiar with new clinical problems in multiple organ systems and anticipate issues provoked by adolescence and physical growth. During this period of transitional care the clinician or team assists young patients to build attitudes, skills and understanding of processes needed to maximize function of their urinary tract-thus taking responsibility for their own healthcare needs. Preparation must also address, negotiating adult health care systems, psychosocial, educational or vocational issues, and mental wellbeing. CONCLUSIONS: Transitioning and transfer of children with major congenital anomalies to clinicians potentially unfamiliar with their conditions requires improved education both for receiving doctors and children's families. Early initiation of the transition process should allow the transference to take place at appropriate times based on the child's development, and environmental and financial factors. Neurourol. Urodynam. 36:811-819, 2017. © 2016 Wiley Periodicals, Inc.

Does intracytoplasmic sperm injection pose an increased risk of genitourinary congenital malformations in offspring compared to in vitro fertilization? A systematic review and meta-analysis.

PURPOSE: We systematically reviewed and performed a meta-analysis of the genitourinary congenital malformation rate after conception by intracytoplasmic sperm injection compared to in vitro fertilization. MATERIALS AND METHODS: We systematically reviewed studies to compare perinatal outcomes between children conceived by intracytoplasmic sperm injection vs in vitro fertilization. Studies showing genitourinary congenital malformation rates were included. We assessed the risk of bias, focusing on the quality of genitourinary congenital malformation reporting and analysis targeted at singletons. Meta-analysis was done using a random effects model for 3 outcomes, including overall genitourinary congenital malformation, hypospadias and cryptorchidism. Sensitivity analysis was also performed in only studies at low risk for bias. RESULTS: The initial search yielded 1,482 articles. We performed a full text review of 111 of these studies, of which 22 met inclusion criteria for systematic review. Meta-analysis of intracytoplasmic sperm injection and in vitro fertilization in 12,270 and 24,240 cases, respectively, revealed that intracytoplasmic sperm injection was associated with a significantly higher rate of overall genitourinary congenital malformation compared to in vitro fertilization (OR 1.27, 95% CI 1.02-1.59, p = 0.04). However, when including only 4 studies at low risk for bias with a total of 7,727 and 14,308 intracytoplasmic sperm injection and in vitro fertilization cases, respectively, the difference was not significant (OR 1.28, 95% CI 1.00-1.64, p = 0.05). There was no statistically significant difference in the rate of hypospadias (OR 1.21, 95% CI 0.87-1.69) or cryptorchidism (OR 1.39, 95% CI 0.97-2.00) between males conceived by intracytoplasmic sperm injection vs in vitro fertilization. On all analyses there was no significant statistical heterogeneity between studies (I(2) = 0). CONCLUSIONS: Intracytoplasmic sperm injection is associated with a slightly higher risk of genitourinary malformation in offspring than in vitro fertilization. However, when only higher quality studies were analyzed, the difference was not significant. The hypospadias and cryptorchidism rates in offspring are similar for the 2 conception methods.

Redo surgery to improve urinary function, sexual function and cosmesis in male patients with exstrophy-epispadias complex complications. Technical principles and pearls based on case scenarios.

The bladder exstrophy-epispadias complex includes some of the most challenging conditions treated by pediatric urologists. They are associated with the need for multiple intricate reconstructive procedures, aimed at restoring the anatomy and function of the bladder, urethra and external genitalia. These patients often endure multiple redo reconstructive procedures to improve urinary function, sexual function and cosmesis throughout the first two decades of life. In this article, we present the 30-year experience of a single surgeon performing redo surgery for males born with epispadias and bladder exstrophy. Through detailed documentation of 6 clinical cases, we highlight technical aspects that may contribute to a successful surgical reconstruction in these patients. The article is focused specifically on patients undergoing redo epispadias repair with or without concomitant continence procedures. We make the case for complete penile disassembly with external rotation of the corpora to correct recurrent dorsal curvature; this approach also allows the surgeon to have access to the proximal urethra and bladder neck after opening the intersymphiseal scar/band. This is useful when additional procedures on the bladder, such as bladder neck tailoring, are necessary. We also highlight the importance of avoiding reverse Byars' flaps when performing skin closure, due to the resulting midline scar. Besides being associated with a poor cosmetic outcome, it can also contribute to recurrent dorsal curvature. The authors advocate for rotational skin flaps to cover the penile shaft. Correction of dorsal curvature and improved cosmesis obtained with complete penile disassembly sometimes comes at the expense of the urethra being left as a hypospadias (figure). This will require further surgeries (usually a 2-stage buccal mucosa graft), much like the treatment of proximal hypospadias. Redo epispadias surgery in males remains a challenge. The systematic approach offered by the case scenarios may help guide surgeons dealing with this difficult condition. Patient with complications after repair of classic bladder exstrophy. A) Stone retrieved from posterior urethra after complete penile disassembly. B) After opening the inter-symphiseal scar, the bladder has been opened and the bladder neck tailored. C) Complete penile disassembly has been completed with corporal bodies and urethra individualized. D,E,F) Final appearance of the repair; abdominal wall was closed with anterior rectus sheath flaps, penile skin was closed with rotational flaps and urethra ended up as a hypospadias.