BACKGROUND: To review race and ethnic group enrollment and outcomes for Wilms tumor (WT) across all 4 risk-assigned therapeutic trials from the current era Children’s Oncology Group Renal Tumor Biology and Risk Stratification Protocol, AREN03B2. STUDY DESIGN: For patients with WT enrolled in AREN03B2 (2006 to 2019), disease and biologic features, therapeutic study-specific enrollment, and event-free (EFS) and overall (OS) 4-year survival were compared between institutionally reported race and ethnic groups. RESULTS: Among 5,146 patients with WT, no statistically significant differences were detected between race and ethnic groups regarding subsequent risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or overall EFS or OS, except the following variables: Black children were older and had larger tumors at enrollment, whereas Hispanic children had lower rates of diffuse anaplasia WT and loss of heterozygosity at 1p. The only significant difference in EFS or OS between race and ethnic groups was observed among the few children treated for diffuse anaplasia WT with regimen UH-1 and -2 on high-risk protocol, AREN0321. On this therapeutic arm only, Black children showed worse EFS (hazard ratio = 3.18) and OS (hazard ratio = 3.42). However, this finding was not replicated for patients treated with regimen UH-1 and -2 under AREN03B2 but not on AREN0321. CONCLUSIONS: Race and ethnic group enrollment appeared constant across AREN03B2 risk-assigned therapeutic trials. EFS and OS on these therapeutic trials when analyzed together were comparable regarding race and ethnicity. Black children may have experienced worse stage-specific survival when treated with regimen UH-1 and -2 on AREN0321, but this survival gap was not confirmed when analyzing additional high-risk AREN03B2 patients.

Children with renal masses require surgical management to provide accurate surgical staging and skilled resection of the tumor. This document includes evidence-based recommendations for pediatric surgeons regarding the resection, staging, and proper nodal basin evaluation.

This study comprehensively evaluated the landscape of genetic and epigenetic events that predispose to synchronous bilateral Wilms tumor (BWT). We performed whole exome or whole genome sequencing, total-strand RNA-seq, and DNA methylation analysis using germline and/or tumor samples from 68 patients with BWT from St. Jude Children’s Research Hospital and the Children’s Oncology Group. We found that 25/61 (41%) of patients evaluated harbored pathogenic or likely pathogenic germline variants, with WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%) and the BRCA-related genes (5%) BRCA1 , BRCA2 , and PALB2 being most common. Germline WT1 variants were strongly associated with somatic paternal uniparental disomy encompassing the 11p15.5 and 11p13/ WT1 loci and subsequent acquired pathogenic CTNNB1 variants. Somatic coding variants or genome-wide copy number alterations were almost never shared between paired synchronous BWT, suggesting that the acquisition of independent somatic variants leads to tumor formation in the context of germline or early embryonic, post-zygotic initiating events. In contrast, 11p15.5 status (loss of heterozygosity, loss or retention of imprinting) was shared among paired synchronous BWT in all but one case. The predominant molecular events for BWT predisposition include pathogenic germline variants or post-zygotic epigenetic hypermethylation at the 11p15.5 H19/ICR1 locus (loss of imprinting). This study demonstrates that post-zygotic somatic mosaicism for 11p15.5 hypermethylation/loss of imprinting is the single most common initiating molecular event predisposing to BWT. Evidence of somatic mosaicism for 11p15.5 loss of imprinting was detected in leukocytes of a cohort of BWT patients and long-term survivors, but not in unilateral Wilms tumor patients and long-term survivors or controls, further supporting the hypothesis that post-zygotic 11p15.5 alterations occurred in the mesoderm of patients who go on to develop BWT. Due to the preponderance of BWT patients with demonstrable germline or early embryonic tumor predisposition, BWT exhibits a unique biology when compared to unilateral Wilms tumor and therefore warrants continued refinement of its own treatment-relevant biomarkers which in turn may inform directed treatment strategies in the future.

OBJECTIVE:To describe the changes to routine pediatric surgical care over the past 2 decades for children living in urban and rural environments. BACKGROUND:A knowledge gaps exists regarding trends in the location where routine pediatric surgical care is provided to children from urban and rural environments over time. METHODS:Children (age 0-18) undergoing 7 common surgeries were identified using State Inpatient Databases (SID, 2002-2017). Rural-Urban Commuting Area codes were used to classify patient and hospital zip codes. Multivariable regression models for distance traveled >60 miles and transfer status were used to compare rural and urban populations, adjusting for year, age, sex, race, and insurance status. RESULTS:Among 143,467 children, 13% lived in rural zip codes. The distance traveled for care increased for both rural and urban children for all procedures but significantly more for the rural cohort (eg, 102% vs 30%, P <0.001, cholecystectomy). Transfers also increased for rural children (eg, transfers for appendectomy increased from 1% in 2002 to 23% in 2017, P <0.001). Factors associated with the need to travel >60 miles included year [adjusted odds ratio (aOR)=2.18, 95% CI: 1.94-2.46: 2017 vs 2002], rural residence (aOR=6.55, 95% CI: 6.11-7.01), age less than 5 years (aOR=2.17, 95% CI: 1.92-2.46), and Medicaid insurance (aOR=1.35, 95% CI: 1.26-1.45). Factors associated with transfer included year (aOR=5.77, 95% CI: 5.26-6.33: 2017 vs 2002), rural residence (aOR=1.47, 95% CI: 1.39-1.56), age less than 10 years (aOR=2.34, 95% CI: 2.15-2.54), and Medicaid insurance (aOR=1.49, 95% CI: 1.42-1.46). CONCLUSION:Rural children, younger age, and those on Medicaid disproportionately traveled greater distances and were more frequently transferred for common pediatric surgical procedures.

10005 Background: FAWT represents tumors with circumscribed small areas of anaplastic nuclear changes confined to the kidney within an otherwise favorable histology WT. In National Wilms Tumor Study-5, patients with stage I FAWT treated with vincristine and dactinomycin (VA) without flank radiation had 4-year event-free survival (EFS) and overall survival (OS) of 67.5% and 88.9%, respectively. Patients with stage II-IV FAWT were treated with VA plus doxorubicin and radiation (DD4A). Of the 20 patients with stage II-III FAWT, 4 had a relapse and 3 died. The 4-year EFS and OS for stage IV FAWT/upfront nephrectomy were 61.4% and 71.6%, respectively. The COG AREN0321 study evaluated whether intensifying therapy for stage I and IV FAWT would improve survival of these patients. Methods: Tumor histology and stage were confirmed for all patients by real-time central pathology, surgery, and radiology review on protocol AREN03B2, the COG renal tumor classification, biology, and banking study. Patients then enrolled on AREN0321 with stage I-III FAWT received DD4A and those with stage IV FAWT received vincristine, doxorubicin, cyclophosphamide, carboplatin and etoposide with radiation (UH-1). We analyzed outcomes of patients with FAWT treated on AREN0321 and those enrolled only on AREN03B2 who received the same chemotherapy regimens. Results: A total of 46 patients (25 AREN0321 and 21 AREN03B2) were included in the analyses. Of the 25 AREN0321 patients, 17 (68%) had upfront nephrectomy and all 25 received radiation. Of the 5 AREN0321 patients with stage IV FAWT, 4 had metastasis to lung and 1 to lung and liver. Of the 21 AREN03B2 patients, 19 (90%) had upfront nephrectomy and 17 (81%) reported receiving radiation. The 2 AREN03B2 stage IV patients had lung only metastases. The 4-year EFS and OS are displayed in the table below. No events occurred in stage I-II AREN0321 patients nor in any AREN03B2 patients. Of 10 patients with stage III FAWT on AREN0321, 3 had a relapse. None of the 7 stage IV FAWT patients who received UH-1 had a relapse, but one patient died due to toxicity. Conclusions: Patients with stage I and II FAWT had outstanding survival when treated with DD4A and radiation. Intensification of therapy may be warranted for stage III FAWT and appears to have improved patient survival for stage IV FAWT but with increased risk of toxicity. Strategies to alleviate toxicity of UH-1 therapy have been incorporated into the ongoing COG trial for high-risk patients. Clinical trial information: NCT00335556 . [Table: see text]

Background and Aims: Pediatric neuroendocrine tumors (NET) of the GI tract are rare and appendiceal NET are typically incidental. Few studies have been done in the pediatric population and practice guidelines are mainly based on adult data. There are currently no diagnostic studies specific for NET. Our study aimed to identify clinical, radiological, and pathological findings in pediatric appendiceal NET, test criteria for follow up surgical treatment, review potential prognostic pathological findings, and possible pre-operative diagnostic radiological studies. Materials and Methods: A retrospective data search was conducted for well-differentiated NET of the appendix in patients ≤21 years between 1/1/2003 and 7/1/2022. Available clinical, radiologic, pathological, and follow-up information was recorded. Results: Thirty-seven patients with appendiceal NET were identified. No masses were reported in the patients who underwent presurgical imaging. Appendectomy samples showed NET (0.2–>4 cm), most located in the tip. Most cases were WHO G1 (34/37), with negative margins (n = 25). Sixteen cases extended to the subserosa/mesoappendix (pT3). Lymphovascular (6), perineural (2), and both lymphovascular and perineural invasion were also noted (2). The specified tumor stages were pT1 (10/37), pT3 (16/37), and pT4 (4/37). Patients who underwent laboratory testing for chromogranin A (20) and urine 5HIAA (11) had normal limits. Subsequent surgical resection was recommended in 13 cases and performed in 11. To date, all patients have no recurrent or additional metastatic disease. Conclusions: Our study showed that all pediatric well-differentiated appendiceal NET were incidentally found as part of acute appendicitis management. Most NET were localized with low-grade histology. Our small cohort support the previously suggested management guidelines with follow up resection in certain cases. Our radiologic review didn’t identify a best modality for NET. Comparing cases with and without metastatic disease, no tumors under 1 cm had metastasis, but serosal and perineural invasion along with G2 status were associated with metastasis in our limited study.

ObjectivesThe objectives are to examine the prevalence and characteristics of newly detected psychiatric diagnoses (NDPD) among Medicaid-enrolled children within 1 year after a firearm injury compared to children with a motor vehicle collision (MVC) injury, and how the odds of NDPD varies by diagnosis type.MethodsWe performed a matched case-control retrospective study of children aged 3 to 17 years, using Medicaid MarketScan claims data (2010-2016). Children with firearm injury (n = 1450) were matched 1:3 to children with an MVC injury (n = 3691) by age (in years), sex, and season of index injury. Indicators of clinical severity were the injury severity score (ISS), emergency department (ED) disposition (home, admit to floor or intensive care unit [ICU]), and chronic disease status before and after the injury (utilizing complex chronic condition [CCC] classification schema). Multivariable logistic regression modeling compared OR for NDPD 1-year postinjury, adjusting for race and ethnicity, injury severity, and CCC.ResultsChildren with firearm injuries had 1.5 times greater odds of having NDPD 1-year postinjury compared to children with an MVC injury (adjusted OR [aOR] = 1.55 [95% CI, 1.33-1.80]). Children who were hospitalized following a firearm injury had almost 2 times the odds of having an NDPD (floor: aOR = 1.80 [95% CI, 1.47-2.22]; ICU: aOR = 1.78 [95% CI, 1.22-2.59]) compared to children discharged from the ED postinjury. Increased odds of NDPD after firearm injury was driven by increases in substance-related and addictive disorders (aOR = 2.08 [95% CI, 1.63-2.64]) and trauma- and stressor-related disorders (aOR = 2.07 [95% CI, 1.55-2.76]).ConclusionsChildren had 50% increased odds of having an NDPD in the year following a firearm injury as compared to those with an MVC injury. Priority should be placed on the delivery of evidence-based treatments for substance use and trauma exposure among new users of outpatient mental health care following a firearm injury.TRA, PTSD, SUD ObjectivesThe objectives are to examine the prevalence and characteristics of newly detected psychiatric diagnoses (NDPD) among Medicaid-enrolled children within 1 year after a firearm injury compared to children with a motor vehicle collision (MVC) injury, and how the odds of NDPD varies by diagnosis type. The objectives are to examine the prevalence and characteristics of newly detected psychiatric diagnoses (NDPD) among Medicaid-enrolled children within 1 year after a firearm injury compared to children with a motor vehicle collision (MVC) injury, and how the odds of NDPD varies by diagnosis type. MethodsWe performed a matched case-control retrospective study of children aged 3 to 17 years, using Medicaid MarketScan claims data (2010-2016). Children with firearm injury (n = 1450) were matched 1:3 to children with an MVC injury (n = 3691) by age (in years), sex, and season of index injury. Indicators of clinical severity were the injury severity score (ISS), emergency department (ED) disposition (home, admit to floor or intensive care unit [ICU]), and chronic disease status before and after the injury (utilizing complex chronic condition [CCC] classification schema). Multivariable logistic regression modeling compared OR for NDPD 1-year postinjury, adjusting for race and ethnicity, injury severity, and CCC. We performed a matched case-control retrospective study of children aged 3 to 17 years, using Medicaid MarketScan claims data (2010-2016). Children with firearm injury (n = 1450) were matched 1:3 to children with an MVC injury (n = 3691) by age (in years), sex, and season of index injury. Indicators of clinical severity were the injury severity score (ISS), emergency department (ED) disposition (home, admit to floor or intensive care unit [ICU]), and chronic disease status before and after the injury (utilizing complex chronic condition [CCC] classification schema). Multivariable logistic regression modeling compared OR for NDPD 1-year postinjury, adjusting for race and ethnicity, injury severity, and CCC. ResultsChildren with firearm injuries had 1.5 times greater odds of having NDPD 1-year postinjury compared to children with an MVC injury (adjusted OR [aOR] = 1.55 [95% CI, 1.33-1.80]). Children who were hospitalized following a firearm injury had almost 2 times the odds of having an NDPD (floor: aOR = 1.80 [95% CI, 1.47-2.22]; ICU: aOR = 1.78 [95% CI, 1.22-2.59]) compared to children discharged from the ED postinjury. Increased odds of NDPD after firearm injury was driven by increases in substance-related and addictive disorders (aOR = 2.08 [95% CI, 1.63-2.64]) and trauma- and stressor-related disorders (aOR = 2.07 [95% CI, 1.55-2.76]). Children with firearm injuries had 1.5 times greater odds of having NDPD 1-year postinjury compared to children with an MVC injury (adjusted OR [aOR] = 1.55 [95% CI, 1.33-1.80]). Children who were hospitalized following a firearm injury had almost 2 times the odds of having an NDPD (floor: aOR = 1.80 [95% CI, 1.47-2.22]; ICU: aOR = 1.78 [95% CI, 1.22-2.59]) compared to children discharged from the ED postinjury. Increased odds of NDPD after firearm injury was driven by increases in substance-related and addictive disorders (aOR = 2.08 [95% CI, 1.63-2.64]) and trauma- and stressor-related disorders (aOR = 2.07 [95% CI, 1.55-2.76]). ConclusionsChildren had 50% increased odds of having an NDPD in the year following a firearm injury as compared to those with an MVC injury. Priority should be placed on the delivery of evidence-based treatments for substance use and trauma exposure among new users of outpatient mental health care following a firearm injury.TRA, PTSD, SUD Children had 50% increased odds of having an NDPD in the year following a firearm injury as compared to those with an MVC injury. Priority should be placed on the delivery of evidence-based treatments for substance use and trauma exposure among new users of outpatient mental health care following a firearm injury.

Childhood lymphomas are divided into two broad categories, Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Children and adolescents with HL are divided into three risk categories based on clinical and pathologic staging data, histology, stage at presentation, presence or absence of B symptoms, number of involved sites, and/or presence of bulky disease. Lymphocyte-predominant Hodgkin disease is recognized as a distinct clinicopathological entity, with a favorable outcome, but also associated with a higher risk of late relapse and subsequent development of NHL. HL is derived from a transformed B cell that has undergone monoclonal expansion. Classic cells include Reed-Sternberg, lymphocytic, and histiocytic cells. Immune system dysfunction is hypothesized to be one of the primary causes for HL. Lymphoma must be considered in any child with lymphadenopathy. Patients most frequently present primarily with cervical and or supraclavicular lymphadenopathy. Enlarged axillary nodes or inguinal nodes are less common.

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.

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.

A challenge when repairing imperforate anus is positioning the neo-rectum into the center of the sphincter muscle complex (SMC) with limited muscle injury and scarring. Unfortunately, the path through the components of the SMC are often non-linear. We have used MRI to delineate the complex and guide the needle through the center using standard MRI-guidance (Raschbaum GR et al. J Pediatr Surg 45:220-223, 2010; Thomas TT et al. J Pediatr Surg 35:927–930, 2000). However, asynchronous scanning requires multiple, time-consuming scans to advance the needle in stepwise fashion. Asynchronous scanning also prevents visualizing the needle as it is advanced. We recently integrated software into the MRI operative suite that allows placement of the needle with real-time MRI. We report the feasibility and utility of real-time MRI-assisted laparoscopic assisted anorectoplasty (RT MRI-LAARP). Needle guidance was performed with Siemens Espree 1.5 T MRI with T1 Flash RT Sequence. After needle placement, laparoscopic mobilization, fistula takedown and pull-through was performed using the needle to guide dilation to create a tract to pull-through the neo-rectum. Charts of patients who underwent RT MRI-LAARP were reviewed. Demographics, anatomy, number of needle passes, OR duration and complications are reported. There were five children that underwent RT MRI-LAARP; one was a redo secondary to a retracted rectovestibular fistula. Operative time ranged from 187–505 min. Average hospital stay was 4.0 ± 1.0 days. There were no intraoperative complications although one patient had temporary urinary retention post-op. Muscle sparring laparoscopic anorectoplasty using real-time MRI is feasible and facilitates needle placement through the SMC.

Background To the authors' knowledge, AREN0321 is the first prospective clinical study of pediatric and adolescent renal cell carcinoma (RCC). Goals of the study included establishing epidemiological, treatment, and outcome data and confirming that patients with completely resected pediatric RCC, including lymph node-positive disease (N1), have a favorable prognosis without adjuvant therapy. Methods From 2006 to 2012, patients aged <30 years with centrally reviewed pathology of RCC were enrolled prospectively. Results A total of 68 patients were enrolled (39 of whom were male; median age of 13 years [range, 0.17-22.1 years]). Stage was classified according to the American Joint Committee on Cancer TNM stage seventh edition as stage I in 26 patients, stage II in 7 patients, stage III in 26 patients, and stage IV in 8 patients, and was not available in 1 patient. Sixty patients underwent resection of all known sites of disease, including 2 patients with stage IV disease. Surgery included radical nephrectomy (53 patients [81.5%]), partial nephrectomy (12 patients [18.5%]), and unknown (3 patients [4.4%]). Histology was TFE-associated RCC (translocation-type RCC; tRCC) in 40 patients, RCC not otherwise specified and/or other in 13 patients, papillary RCC in 9 patients, and renal medullary carcinoma (RMC) in 6 patients. Lymph node status was N0 in 21 patients, N1 in 21 patients (tRCC in 15 patients, RMC in 3 patients, papillary RCC in 2 patients, and not otherwise specified and/or other in 1 patient), and Nx in 26 patients. The 4-year event-free survival and overall survival rates were 80.2% (95% CI, 69.6%-90.9%) and 84.8% (95% CI, 75.2%-94.5%), respectively, overall and 87.5% (95% CI, 68.3%-100%) and 87.1% (95% CI, 67.6%-100%), respectively, for the 16 patients with N1M0 disease. Among patients presenting with metastases, 2 of 8 patients (2 of 5 patients with RMC) were alive (1 with disease) at the time of last follow-up, including 1 patient who was lost to follow-up (succinate dehydrogenase deficiency). The predominant RCC subtypes associated with mortality were tRCC and RMC. Conclusions Favorable short-term outcomes can be achieved without adjuvant therapy in children and adolescents with completely resected RCC, independent of lymph node status. A prospective study of patients with tRCC and RMC with M1 or recurrent disease is needed to optimize treatment.

We appreciate the letter written by Dr. Taghavi in response to our article regarding lymph node (LN) yield for staging in favorable histology Wilms tumor (WT) [ [1] Saltzman A.F. Smith D.E. Gao D. et al. How many lymph nodes are enough? assessing the adequacy of lymph node yield for staging in favorable histology Wilms tumor. J Pediatr Surg. 2019; S0022346819304075https://doi.org/10.1016/j.jpedsurg.201E9.06.010 Crossref Google Scholar ]. This letter raises some very thoughtful and insightful points on the assessment of LNs for staging of WT.

ABSTRACTObjective:Hirschsprung‐associated enterocolitis (HAEC) is the most frequent complication in Hirschsprung disease (HSCR) patients. Currently HAEC is diagnosed clinically, leaving uncertainty in the diagnosis thereby potentially leading to over‐ or undertreatment of patients. The aim of this study was to identify immune biomarkers to aid in the diagnosis of HAEC.Methods:From 2012 to 2017, 43 children with HSCR enrolled in a multicenter study, underwent retrospective evaluation of their medical records, and questionnaire‐directed parent interviews. HAEC status was determined using HAEC score with cutoff ≥4. Plasma was collected and analyzed by ELISA for the inflammatory bowel disease–associated antibodies: anti‐Saccharomyces cerevisiae mannan antibodies (ASCA), outer membrane porin C (OmpC), CBir1, antineutrophil cytoplasmic antibodies. Data were analyzed using t test, univariate, multivariable, and binomial regression models.Results:Eighteen patients had at least 1 episode of HAEC, 25 had no history of HAEC. The HAEC and NO HAEC groups had similar median ages (3 years) and family histories of HSCR. The HAEC group showed markedly elevated ASCA IgA and OmpC antibody levels compared with the NO HAEC group, whereas CBir1 and antineutrophil cytoplasmic antibodies were similar between the groups. Both univariate and multivariable analysis revealed higher OmpC antibody levels associated with HAEC (odds ratio 1.39, confidence interval 1–1.92, P = 0.048), whereas univariate analysis identified a trend toward elevated IgA and immunoglobulin G ASCA levels with HAEC.Conclusions:We identified elevated OmpC and ASCA serum antibody levels in HAEC patients, and that increased OmpC antibody levels correlated with HAEC occurrence, suggesting HAEC and Crohn disease share gut microbial‐host immune responses. These antibodies may serve as potential biomarkers for HAEC, although prospective study with larger sample size is needed.

Neuroblastoma is an embryonic cancer arising from neural crest stem cells. This cancer is the most common malignancy in infants and the most common extracranial solid tumor in children. The clinical course may be highly variable with the possibility of spontaneous regression in the youngest patients and increased risk of aggressive disease in older children. Clinical heterogeneity is a consequence of the diverse biologic characteristics that determine patient risk and survival. This review will focus on current progress in neuroblastoma staging, risk stratification, and treatment strategies based on advancing knowledge in tumor biology and genetic characterization. TYPE OF STUDY: Review article. LEVEL OF EVIDENCE: Level II.

Patients with vestibular fistula have a good functional outcome after posterior sagittal anorectoplasty (PSARP). While continence is often preserved, close follow-up and management of constipation are often required. Redo anorectal surgery has been associated with worse functional outcomes compared with primary procedures, possibly due to injury and scarring of the pelvic floor musculature and sphincter complex. Our group has a growing experience in the use of intraoperative real-time magnetic resonance imaging (MRI) for anorectal malformation repairs. We present a case of salvage operation of a failed PSARP for vestibular fistula.

PURPOSE:In National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy.METHODS:Patients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies.RESULTS:LOH1p/16q was detected in 49 of 1,147 evaluable patients with stage I/II disease (4.27%) enrolled in AREN03B2; 32 enrolled in AREN0532. LOH1p/16q was detected in 82 of 1,364 evaluable patients with stage III/IV disease (6.01%) in AREN03B2; 51 enrolled in AREN0533. Median follow-up for 83 eligible patients enrolled in AREN0532/0533 was 5.73 years (range, 2.84 to 9.63 years). The 4-year EFS for patients with stage I/II and stage III/IV disease with LOH1p/16 was 87.3% (95% CI, 75.1% to 99.5%) and 90.2% (95% CI, 81.8% to 98.6%), respectively. These results are improved compared with the NWTS-5 updated 4-year EFS of 68.8% for patients with stage I/II disease (P = .042), and 61.3% for patients with stage III/IV disease (P = .001), with trends toward improved 4-year overall survival. The most common grade 3 or higher nonhematologic toxicities with regimen M were febrile neutropenia (39.2%) and infections (21.6%).CONCLUSION:Augmentation of therapy improved EFS for patients with favorable histology Wilms tumor and LOH1p/16q compared with the historical NWTS-5 comparison group, with an expected toxicity profile.

The advances in pediatric cancer far exceed those achieved in adults. The success in improving survival and minimizing late effects has been due to several reasons but work of the pediatric cancer cooperative groups is a primary. These cooperative groups are multidisciplinary with medical oncologists, pathologists, radiologists, surgeons, radiation oncologists, scientists and most importantly the patients and families. Studies have expanded from regional to national and now international studies which continue to target problems pertinent to improving the outcome for children with cancer. In this article we review the history of the cooperative groups, a selection of seminal studies pertaining to solid tumors, future challenges and collaborations.

10516 Background: Although renal cell carcinoma (RCC) is the second most common pediatric kidney cancer, no previous prospective clinical trials have been conducted. AREN0321 tested the hypothesis that RCC with localized completely resected disease, including those with lymph node involvement, has a favorable prognosis without adjuvant medical therapy. Methods: From 2006 to 2012, patients up to age 30 years with centrally reviewed pathology confirmation of RCC were prospectively enrolled. Patients with completely resected disease were followed without adjuvant therapy, independent of TNM stage. Results: 62 eligible patients enrolled (35 male: 27 female; median age 13.2 yr (range 0.17 - 22.1)). Histology was TFE-associated RCC (TRCC; 33, 53.2%), RCC NOS (21, 33.9%), papillary RCC (5, 8.1%) and Renal Medullary Carcinoma (RMC; 3, 4.8%). 58 (93.5%) patients had all disease completely resected at diagnosis with stages 1 (27, 43.5%), 2 (7, 11.3%), and 3 (24, 38.7%) disease. Three patients with stage 4 (M1) and one with stage 3 had an incomplete resection. Surgery included radical nephrectomy (50) and partial nephrectomy (12). Lymph node (LN) status was N0 (21 (33.9%)), N1 (19 (30.6%)), and Nx (22 (35.5%)). Histology for patients with N1 disease was: TRCC (13, 68.4%), RCC NOS (4, 21.1%) and RMC (2, 10.5%). Four-year EFS and OS for the completely resected group were: 87.2% (95% CI 77.0 – 97.4) and 94.6% (87.6-100), respectively; and by stage were: 1 (92.4% (80.7-100) and 96.2% (87.7-100)), 2 (100% and 100%), and 3 (77.6% (57.6 – 97.6) and 91.3% (77.1-100)) (EFS p-value 0.294, OS p-value 0.722). Four-year EFS and OS by histology for the overall group were: TRCC: 87.7% (74.2-100) and 93.6% (83.3-100), papillary RCC: 100% and 100%, RCC NOS: 87.7% (70.3-100) and 100%, and RMC: 33.3% (0-86.7) and 33.3% (0-86.7). For the 15 patients with completely resected N1M0 disease (of which 13 had TRCC), the four-year EFS and OS were 86.7% (64.7-100) and 93.3% (76.6-100), respectively. Conclusions: Favorable outcomes can be achieved without adjuvant therapy in children and adolescents with completely resected RCC, including those with locally advanced disease and lymph node involvement. Clinical trial information: NCT00335556.