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.

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.

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.

Wilms Tumor.

Wilms tumor (WT), or nephroblastoma, is the most common primary malignant renal tumor of childhood. It is an embryonal tumor that develops from remnants of immature kidney. There are approximately 500 new WT cases diagnosed in the United States every year. Advances in multimodal therapy including surgery, chemotherapy, and radiation therapy given according to risk stratification have allowed most patients to achieve survival rates in excess of 90%.

Diagnosis, Classification, and Contemporary Management of Undescended Testicles.

This article provides a comprehensive review regarding undescended testicles and other related conditions. We have included background information summarizing variable clinical presentations, epidemiology, and the implications of undescended testis (UDT) on fertility and malignancy risk. This article has an emphasis on the approach to diagnosis and surgical management for the UDT. The purpose of this review is to provide readers with useful clinical tools for assessing and treating patients with cryptorchidism.

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.

Outcomes according to treatment using an established protocol in patients with bilateral Wilms' tumor: A national Canadian population-based study.

BACKGROUND: Bilateral Wilms tumor (BWT) is a rare entity. The goal of this study is to report outcomes (overall and event-free survival, OS/EFS) of BWT in a large cohort representative of the Canadian population since 2000. We focused on the occurrence of late events (relapse or death beyond 18 months), as well as outcomes of patients treated following the only protocol specifically designed for BWT to date, AREN0534, compared to patients treated following other therapeutic schemes. METHODS: Data was obtained for patients diagnosed with BWT between 2001 and 2018 from the Cancer in Young People in Canada (CYP-C) database. Demographics, treatment protocols, and dates for events were collected. Specifically, we examined outcomes of patients treated according to the Children's Oncology Group (COG) protocol AREN0534 since 2009. Survival analysis was performed. RESULTS: 57/816 (7%) of patients with Wilms tumor had BWT during the study period. Median age at diagnosis was 2.74 years (IQR 1.37-4.48) and 35 (64%) were female; 8/57 (15%) had metastatic disease. After a median follow-up of 4.8 years (IQR 2.8-5.7 years, range 0.2-18 years), OS and EFS were 86% (CI 73-93%) and 80% (CI 66-89%), respectively. Less than 5 events were recorded after 18 months from diagnosis. Since 2009, patients treated according to the AREN0534 protocol had a statistically significant higher OS compared to patients treated with other protocols. CONCLUSIONS: In this large Canadian cohort of patients with BWT, OS and EFS compared favorably to the published literature. Late events were rare. Patients treated according to a disease-specific protocol (AREN0534) had improved overall survival. TYPE OF STUDY: Original article. LEVEL OF EVIDENCE: Level IV.

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.

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.

Shared decision-making for pediatric elective penile surgery.

INTRODUCTION: In pediatric surgery, proxy decision-makers are frequently involved in treatment planning and may experience decisional conflict (DC). Shared decision-making (SDM) approaches may be effective to remedy DC. This study investigates DC and SDM involvement in elective pediatric penile surgery. METHODS: Forty-four parents of children aged <8 years undergoing elective penile surgery consultations at a tertiary pediatric hospital were prospectively enrolled. Patient and physician questionnaires were used to assess the SDM process and the SURE (Sure of myself; Understand information; Risk-benefit ratio; Encouragement) screening test was used to assess DC. RESULTS: Thirty-seven (84.1%) mothers and seven (15.9%) fathers were enrolled for circumcision (n=33, 75.0%) and distal hypospadias repair (n=11, 25.0%) consultations, with 21 (47.7%) choosing to proceed with surgery. Seven (15.9%) participants experienced clinically significant DC. Participant gender was not associated with higher levels of DC (p=0.318). The average patient and physician SDM scores were 88.2±10.0 and 85.3±7.4, respectively, with no correlation found between participant and physician perception of SDM involvement (p=0.168, p=0.276). DC was significantly associated with lower participant and physician ratings of SDM. CONCLUSIONS: There was a high perception of SDM involvement by both parents and pediatric urologists regarding elective penile surgery. Of the 15% of parents experiencing DC, there was an association with lower participant and physician levels of SDM involvement. Despite high SDM scores overall, discrepancies exist between the perceived physician and participant SDM involvement.

Concurrent Multicystic Dysplastic Kidney, Posterior Urethral Valves, and Obstructive Ureterocele in a Male Pediatric Patient: A Case Report.

Congenital anomalies of the kidney and urinary tract (CAKUT) are diagnosed in approximately 3-6 per 1000 live births and represent a spectrum of urologic conditions impacting the kidneys, ureter, bladder, and urethra.1 Although both are considered under the classification of CAKUT, there is no known unifying pathophysiologic mechanism for ureteroceles and posterior urethral valves with only 1 case report noted in the literature. Herein we report the only documented case of a patient with CAKUT related to posterior urethral valves, ureterocele, and multicystic dysplastic kidney.

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.

Testicular tumors in children and adolescents: long-term endocrine and fertility issues.

The treatment modalities for testicular tumors (surgery, chemotherapy, and radiotherapy), have different associated gonadotoxic risks and the overall survival for most pediatric patients with testicular tumors is very good. However, necessary treatments may lead to the development of lasting gonadal dysfunction and subsequent negative health and quality of life impact. Research with long-term follow-up for patients who have undergone surgery as the sole treatment modality for testicular tumors in childhood are lacking. It is currently unclear if surgery leads to long-term negative functional outcomes. Alkylating agents (e.g., cyclophosphamide) have long been known to increase risk of infertility; platinum-based therapies used frequently for patients with germ-cell tumors (GCTs) also seem to carry some risk of gonadotoxicity, although they have not been as well studied. Radiotherapy to the gonads is toxic and Leydig cells are particularly sensitive to high doses of radiation (>12 Gy). Long-term fertility and hormonal impact vary based on the patient's age, as well as the type and intensity of the oncological treatment prescribed. Counselling regarding fertility risk and preservation options should ideally take place before initiating potentially gonadotoxic treatments. Hypogonadism in peri-pubertal boys can present as delayed onset or failure to progress through puberty. Sperm cryopreservation should be offered for post-pubertal boys who are able to provide a semen sample. For prepubertal boys or young males who cannot provide a semen sample, only experimental options are currently available. Much of the data reviewed here is extrapolated from research done on adult males whose reproductive and hormonal outcomes may not be comparable to younger patients who do not yet have fully developed reproductive systems. Currently, a lack of good quality evidence in this age range causes this restriction to be unavoidable. Patients and their families want to be informed of the risks and treatment options for preserving testicular function. As research continues in this field, it grows more important for urologists to be aware of the outcomes and options for their patients.

Meeting report on the NIDDK/AUA Workshop on Congenital Anomalies of External Genitalia: challenges and opportunities for translational research.

Congenital anomalies of the external genitalia (CAEG) are a prevalent and serious public health concern with lifelong impacts on the urinary function, sexual health, fertility, tumor development, and psychosocial wellbeing of affected individuals. Complications of treatment are frequent, and data reflecting long-term outcomes in adulthood are limited. To identify a path forward to improve treatments and realize the possibility of preventing CAEG, the National Institute of Diabetes and Digestive and Kidney Diseases and the American Urological Association convened researchers from a range of disciplines to coordinate research efforts to fully understand the different etiologies of these common conditions, subsequent variation in clinical phenotypes, and best practices for long term surgical success. Meeting participants concluded that a central data hub for clinical evaluations, including collection of DNA samples from patients and their parents, and short interviews to determine familial penetrance (small pedigrees), would accelerate research in this field. Such a centralized datahub will advance efforts to develop detailed multi-dimensional phenotyping and will enable access to genome sequence analyses and associated metadata to define the genetic bases for these conditions. Inclusion of tissue samples and integration of clinical studies with basic research using human cells and animal models will advance efforts to identify the developmental mechanisms that are disrupted during development and will add cellular and molecular granularity to phenotyping CAEG. While the discussion focuses heavily on hypospadias, this can be seen as a potential template for other conditions in the realm of CAEG, including cryptorchidism or the exstrophy-epispadias complex. Taken together with long-term clinical follow-up, these data could inform surgical choices and improve likelihood for long-term success.

Point-of-care influences orchiectomy rates in pediatric patients with testicular torsion.

OBJECTIVES: The objective of this study was to determine whether point-of-care (community hospitals vs. tertiary centers) or treatment-delaying variables (transfer, emergency room [ER] throughput, and distance traveled) affect orchiectomy rates in minors with testicular torsion (TT) using a national database. STUDY DESIGN: This was a retrospective cohort study using prospectively collected data by the Canadian Institute of Health Information (CIHI) between 2010 and 2015. All Canadian male patients in the CIHI database aged <18 years with TT based on International Classification of Diseases (ICD) codes were included, except for those residing in Quebec. Variables collected were age, type of treating institution (community small/medium, community large, or tertiary/academic), transfer for definitive treatment, road distance traveled, and ER throughput. The outcome was testicular loss based on intervention codes for orchiectomy/orchidopexy. Univariable and multivariable analyses were performed using logistic regression. RESULTS: A total of 1713 minors with TT were included. Overall orchiectomy rate was 28%. Most patients (52%) were treated at tertiary hospitals. Small/medium community hospitals depicted the lowest odds of orchiectomy on univariable and multivariable analyses (odds ratio [OR] = 0.54, confidence interval [CI]: 0.37-0.79, p < 0.001); academic hospitals were also associated with a lower odds of orchiectomy than large community ones. Transfer and distance traveled were not associated with the outcome. Age >12 and ER throughput less than 1 h were significantly associated with lower orchiectomy rates. In a subgroup analysis of patients aged <12 years (n = 278), transfer was the only factor associated with increased risk of orchiectomy (OR = 2.41 , CI: 1.09-5.33; p = 0.03). DISCUSSION: This study showed that small and medium community hospitals had the lowest orchiectomy rates in minors with TT in Canada (Figure). However, on multivariable analysis, they performed similarly to tertiary/academic hospitals, with both being superior to large community hospitals. Transfer and distance traveled did not affect orchiectomy rates. Emergency room throughput had a statistically significant association with orchiectomy rates in every analysis and based on the study data would constitute the best target for policies aimed at reducing orchiectomy rates for TT in minors. The main limitation of this study is the inability to evaluate long-term testicular viability of patients not undergoing orchiectomy (i.e., true testicular salvage). CONCLUSIONS: Type of hospital treating facility (point-of-care) affects orchiectomy rates in minors with TT. Small/medium community hospitals depict the lowest orchiectomy rates in Canada. Transfer to another facility for definitive care and distance traveled did not affect orchiectomy rates, except in a subgroup analysis of prepubertal boys. Longer ER throughput and prepubertal age were consistently associated with loss of the testicle.

Local control for vaginal botryoid rhabdomyosarcoma with pre-rectal transperineal surgical resection and autologous buccal graft vaginal replacement: A novel, minimally invasive, radiation-sparing approach.

PURPOSE: Localized vaginal rhabdomyosarcoma (RMS) is associated with a favorable prognosis, but strategies for local control remain controversial. The use of radiotherapy (RT) can have important long-term sequelae, while traditional resection involves major reconstructive surgery. We describe a new surgical approach employing a minimally-invasive resection and immediate reconstruction. MATERIALS AND METHODS: Records from 4 consecutive patients with localized vaginal RMS managed in 4 major pediatric referral centers were reviewed. All cases were performed with a standardized technique. RESULTS: Patients were diagnosed at a median age of 24months. Each underwent a total/subtotal vaginectomy with autologous buccal graft vaginal replacement. Final margins were focally positive in one patient and negative in three. None received radiotherapy. To date, all patients have patent buccal neovaginas, enjoy a favorable aesthetic result, and remain disease-free at a median follow-up of 35months. CONCLUSIONS: We report 4 cases of localized vaginal RMS successfully treated with a minimally invasive surgical approach. All patients have avoided radiation and remain disease-free. Our initial data suggest that surgical local control and immediate reconstruction are feasible and can spare these patients the long-term complications of RT. Longer follow-up is critical to ensure disease-free survival with a functional, successfully reconstructed neovagina. TYPE OF STUDY: Case series. LEVEL OF EVIDENCE: Level IV.

The role of adenotonsillectomy in the treatment of primary nocturnal enuresis in children: A systematic review.

INTRODUCTION: Primary nocturnal enuresis (PNE) is a challenging condition for physicians, patients and families. Although the etiology remains unclear, sleep-disordered breathing (SDB) and sleep apnea have been suggested to play an important role. Recent research has suggested a potential therapeutic benefit of adenotonsillectomy (T&A) and surgical management of upper airway obstruction in the treatment of PNE. OBJECTIVE: The aim was to conduct a systematic review of relevant literature to determine the effectiveness of T&A in treating children aged 2-19 years with PNE. STUDY DESIGN: This was a systematic review using a comprehensive electronic search strategy that included PubMed, Embase, CINAHL, Cochrane Library, conference proceedings, and the gray literature up to July 2015. We included all studies of children aged 2-19 years with PNE and SDB who underwent T&A. The primary outcome was resolution of PNE following surgery. Observational studies and randomized trials were reviewed. Risk of bias assessment and meta-analyses of included studies were performed. RESULTS: We screened 3254 citations; following title and abstract screening, 42 studies were selected for full-text screening by two independent reviewers. We included 18 studies (890 patients) in our final analysis. All studies were observational and only one included a control group. Meta-analysis of proportions of all (18) studies revealed a pooled complete resolution rate of 51% (43-60%), with significant heterogeneity among studies (I2 = 82.2%). Partial resolution was seen in 20% (14-27%), with similar heterogeneity to the complete resolution group. Sensitivity analysis including only studies with a low risk of bias and with patients ≥5 years (n = 244 patients) yielded a complete resolution rate of 43% (36-49%) with minimal heterogeneity (I2 = 0%; figure). CONCLUSION: In our systematic review, T&A resulted in improvement of nocturnal enuresis in more than 60% of patients, with complete resolution rates in excess of 50%. Findings were persistent on meta-analysis focused only on studies including older patients (≥5 years) and those with short follow-up after surgery (≤3 months), which imply a higher cure rate than would be expected based on natural history alone. The limitations of this review include the lack of controlled trials, the overall quality of the evidence reviewed and the heterogeneity between included studies. The role for systematic investigation and treatment of sleep disorders in patients with PNE should be scrutinized further, since a near 50% complete resolution rate for PNE may be expected with T&A in some settings.