Central Venous Catheter Consideration in Pediatric Oncology: A Systematic Review and Meta-analysis From the American Pediatric Surgical Association Cancer Committee.

BACKGROUND: Tunneled central venous catheters (CVCs) are the cornerstone of modern oncologic practice. Establishing best practices for catheter management in children with cancer is essential to optimize care, but few guidelines exist to guide placement and management. OBJECTIVES: To address four questions: 1) Does catheter composition influence the incidence of complications; 2) Is there a platelet count below which catheter placement poses an increased risk of complications; 3) Is there an absolute neutrophil count (ANC) below which catheter placement poses an increased risk of complications; and 4) Are there best practices for the management of a central line associated bloodstream infection (CLABSI)? METHODS: Data Sources: English language articles in Ovid Medline, PubMed, Embase, Web of Science, and Cochrane Databases. STUDY SELECTION: Independently performed by 2 reviewers, disagreements resolved by a third reviewer. DATA EXTRACTION: Performed by 4 reviewers on forms designed by consensus, quality assessed by GRADE methodology. RESULTS: Data were extracted from 110 manuscripts. There was no significant difference in fracture rate, venous thrombosis, catheter occlusion or infection by catheter composition. Thrombocytopenia with minimum thresholds of 30,000-50,000 platelets/mcl was not associated with major hematoma. Limited evidence suggests a platelet count <30,000/mcL was associated with small increased risk of hematoma. While few studies found a significant increase in CLABSI in CVCs placed in neutropenic patients with ANC<500Kcells/dl, meta-analysis suggests a small increase in this population. Catheter removal remains recommended in complicated or persistent infections. Limited evidence supports antibiotic, ethanol, or hydrochloric lock therapy in definitive catheter salvage. No high-quality data were available to answer any of the proposed questions. CONCLUSIONS: Although over 15,000 tunneled catheters are placed annually in North America into children with cancer, there is a paucity of evidence to guide practice, suggesting multiple opportunities to improve care. LEVEL OF EVIDENCE: III. This study was registered as PROSPERO 2019 CRD42019124077.

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 clear cell sarcoma of the kidney: A report from the Children's Oncology Group studies AREN0321 and AREN03B2.

BACKGROUND: On the fifth National Wilms Tumor Study, treatment for clear cell sarcoma of the kidney (CCSK) included combined vincristine, doxorubicin, cyclophosphamide, and etoposide (regimen I) plus radiation therapy (RT), yielding 5-year event-free survival (EFS) rates of 100%, 88%, 73%, and 29% for patients who had with stage I, II, III, and IV disease, respectively. In the Children's Oncology Group study AREN0321 of risk-adapted therapy, RT was omitted for stage I disease if lymph nodes were sampled, and carboplatin was added for stage IV disease (regimen UH-1). Patients who had stage II/III disease received regimen I with RT. METHODS: Four-year EFS was analyzed for patients enrolled on AREN0321 and on those enrolled on AREN03B2 who received AREN0321 stage-appropriate chemotherapy. RESULTS: Eighty-two patients with CCSK enrolled on AREN0321, 50 enrolled on AREN03B2 only. The 4-year EFS rate was 82.7% (95% confidence interval [CI], 74.8%-91.4%) for AREN0321 and 89.6% (95% CI, 81.3%-98.7%) for AREN03B2 only (p = .28). When combining studies, the 4-year EFS rates for patients who had stage I (n = 10), II (n = 47), III (n = 65), and IV (n = 10) disease were 90% (95% CI, 73.2%-100.0%), 93.4% (95% CI, 86.4%-100.0%), 82.8% (95% CI, 74.1%-92.6%), and 58.3% (95% CI, 34%-100.0%), respectively. There were no local recurrences among seven patients with stage I disease who were treated without RT. One stage I recurrence occurred in the brain, which was the most common site of relapse overall. Among patients with local stage III tumors, neither initial procedure type, margin status, nor lymph node involvement were prognostic. CONCLUSIONS: Patients with stage I CCSK had excellent outcomes without local recurrences when treated without RT. Patients with stage IV disease appeared to benefit from a carboplatin-containing regimen, although their outcomes remained unsatisfactory. Further research is needed to improve outcomes for patients with advanced-stage disease (ClinicalTrials.gov identifiers NCT00335556 and NCT00898365).

Limited English Proficiency can Negatively Impact Disease/Treatment in Children With Cancer Compared to Those Who are English Proficient-an Institutional Study.

BACKGROUND: In 2013, 25.5 million people in the United States self-identified as having limited English proficiency (LEP). LEP in adults has been associated with longer hospital stays, increased adverse events, increased emergency room visits, and decreased understanding of medications prescribed. This study aims to define the relationship between LEP and outcomes in a pediatric oncologic population. METHODS: We performed a matched case-control study utilizing data from our institutional cancer database (children

Defining Practice Readiness in Pediatric Surgery Fellowship: A Qualitative Analysis.

INTRODUCTION: While competency-based training is at the forefront of educational innovation in General Surgery, Pediatric Surgery training programs should not wait for downstream changes. There is currently no consensus on what it means for a pediatric surgery fellow to be "practice-ready". In this study, we aimed to provide a framework for better defining competency and practice readiness in a way that can support the Milestones system and allow for improved assessment of pediatric surgery fellows. METHODS: For this exploratory qualitative study, we developed an interview guide with nine questions focused on how faculty recognize competency and advance autonomy among pediatric surgery fellows. Demographic information was collected using an anonymous online survey platform. We iteratively reviewed data from each interview to ensure adequate information power was achieved to answer the research question. We used inductive reasoning and thematic analysis to determine appropriate codes. Additionally, the Dreyfus model was used as a framework to guide interpretation and contextualize the responses. Through this method, we generated common themes. RESULTS: A total of 19 pediatric surgeons were interviewed. We identified four major themes from 127 codes that practicing pediatric surgeons associate with practice-readiness of a fellow: skill-based competency, the recognition and benefits of struggle, developing expertise and facilitating autonomy, and difficulties in variability of evaluation. While variability in evaluation is not typically included in the concept of practice readiness, assessment and evaluation were described by study participants as essential aspects of how practicing pediatric surgeons perceive practice readiness and competency in pediatric surgery fellows. Competency was further divided into interpersonal versus technical skills. Sub-themes within struggle included personal and professional struggle, benefits of struggle and how to identify and assist those who are struggling. Autonomy was commonly stated as variable based on the attending. CONCLUSION: Our analysis yielded several themes associated with practice readiness of pediatric surgery fellows. We aim to further refine our list of themes using the Dreyfus Model as our interpretive framework and establish consensus amongst the community of pediatric surgeons in order to define competency and key elements that make a fellow practice-ready. Further work will then focus on establishing assessment metrics and educational interventions directed at achieving such key elements.

Race and Ethnic Group Enrollment and Outcomes for Wilms Tumor: Analysis of the Current Era Children's Oncology Group Study, AREN03B2.

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.

Clinical relevance of inflammation on rectal biopsy for Hirschsprung disease: An outcomes analysis.

OBJECTIVES: Inflammation on diagnostic rectal biopsy for children with suspected Hirschsprung disease (HSCR) is reported on pathology, and its significance is unknown. We describe the management and outcomes of a cohort with inflammation on rectal biopsy compared to those without. Specifically, to address the hypothesis that inflammation on diagnostic biopsy is associated with increased complication rates irrespective of intervention type and timing. METHODS: A single institution retrospective review of children with HSCR who underwent biopsy and endorectal pull-through (ERPT) from 2010 to 2020 was performed. The primary outcome was overall complications at 30-days following ERPT. Secondary outcomes included timing and type of operative intervention as well as postoperative enterocolitis diagnosed within 6-months of ERPT. RESULTS: Forty-nine children were identified; inflammation was present on diagnostic biopsy for 17 children. Those with inflammation were more likely to have clinical evidence of enterocolitis at the time of biopsy (p = 0.001) and were more likely to undergo leveling colostomy before ERPT (p = 0.01). Children with inflammation had a higher anastomotic leak rate (p = 0.04). Subgroup analysis of patients with inflammation undergoing primary ERPT versus leveling colostomy demonstrated no significant difference in outcomes following definitive ERPT. CONCLUSIONS: Our study suggests inflammation on diagnostic rectal biopsy for HSCR is associated with increased anastomotic leak rates. While additional prospective studies are indicated, attention to methods of mitigating inflammation and confirming its resolution before definitive pull-through may be of benefit for improving clinical outcomes in patients found with inflammation on diagnostic rectal biopsy.

How Many Operative Performance Ratings Does a Pediatric Surgery Fellow Need to Be Deemed Practice Ready?

PURPOSE: Identifying the number of cases required for a fellow to achieve competence has been challenging. Workplace-based assessment (WBA) systems make collecting performance data practical and create the opportunity to translate WBA ratings into probabilistic statements about a fellow's likelihood of performing to a given standard on a subsequent assessment opportunity. METHODS: We compared data from two pediatric surgery training programs that used the performance rating scale from the Society for Improving Medical Professional Learning (SIMPL). We used a Bayesian generalized linear mixed effects model to examine the relationship past and future performance for three procedures: Laparoscopic Inguinal Hernia Repair, Laparoscopic Gastrostomy Tube Placement, and Pyloromyotomy. RESULTS: For site one, 26 faculty assessed 9 fellows on 16 procedures yielding 1094 ratings, of which 778 (71%) earned practice-ready ratings. For site two, 25 faculty rated 3 fellows on 4 unique procedures yielding 234 ratings of which 151 (65%) were deemed practice-ready. We identified similar model-based future performance expectations, with prior practice-ready ratings having a similar average effect across both sites (Site one, B = 0.25; Site two, B = 0.25). Similar prior practice-ready ratings were needed for Laparoscopic G-Tube Placement (Site one = 13; Site two = 14), while greater differences were observed for Laparoscopic Inguinal Hernia Repair (Site one = 10; Site two = 15) and Pyloromyotomy (Site one = 10; Site two = 15). CONCLUSION: Our approach to modeling operative performance data is effective at determining future practice readiness of pediatric surgery fellows across multiple faculty and fellow groups. This method could be used to establish minimum case number requirements. TYPE OF STUDY: Original manuscript, Study of Diagnostic Test. LEVEL OF EVIDENCE: II.

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.

Comparison of Outcomes Between Surveillance Ultrasound and Completion Lymph Node Dissection in Children and Adolescents With Sentinel Lymph Node-Positive Cutaneous Melanoma.

OBJECTIVE: To determine the impact of nodal basin ultrasound (US) surveillance versus completion lymph node dissection (CLND) in children and adolescents with sentinel lymph node (SLN) positive melanoma. BACKGROUND: Treatment for children and adolescents with melanoma are extrapolated from adult trials. However, there is increasing evidence that important clinical and biological differences exist between pediatric and adult melanoma. METHODS: Patients ≤18 years diagnosed with cutaneous melanoma between 2010 and 2020 from 14 pediatric hospitals were included. Data extracted included demographics, histopathology, nodal basin strategies, surveillance intervals, and survival information. RESULTS: Of 252 patients, 90.1% (n=227) underwent SLN biopsy (SLNB), 50.9% (n=115) had at least 1 positive node. A total of 67 patients underwent CLND with 97.0% (n=65/67) performed after a positive SLNB. In contrast, 46 total patients underwent US observation of nodal basins with 78.3% (n=36/46) of these occurring after positive SLNB. Younger patients were more likely to undergo US surveillance (median age 8.5 y) than CLND (median age 11.3 y; P =0.0103). Overall, 8.9% (n=21/235) experienced disease recurrence: 6 primary, 6 nodal, and 9 distant. There was no difference in recurrence (11.1% vs 18.8%; P =0.28) or death from disease (2.2% vs 9.7%; P =0.36) for those who underwent US versus CLND, respectively. CONCLUSIONS: Children and adolescents with cutaneous melanoma frequently have nodal metastases identified by SLN. Recurrence was more common among patients with thicker primary lesions and positive SLN. No significant differences in oncologic outcomes were observed with US surveillance and CLND following the identification of a positive SLN.

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.

Diagnostic Performance of Magnetic Resonance Imaging for Pediatric Ovarian Neoplasms: A Multi-Institutional Review.

STUDY OBJECTIVE: To assess the diagnostic performance of MRI to predict ovarian malignancy alone and compared with other diagnostic studies. METHODS: A retrospective analysis was conducted of patients aged 2-21 years who underwent ovarian mass resection between 2009 and 2021 at 11 pediatric hospitals. Sociodemographic information, clinical and imaging findings, tumor markers, and operative and pathology details were collected. Diagnostic performance for detecting malignancy was assessed by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for MRI with other diagnostic modalities. RESULTS: One thousand and fifty-three patients, with a median age of 14.6 years, underwent resection of an ovarian mass; 10% (110/1053) had malignant disease on pathology, and 13% (136/1053) underwent preoperative MRI. MRI sensitivity, specificity, PPV, and NPV were 60%, 94%, 60%, and 94%. Ultrasound sensitivity, specificity, PPV, and NPV were 31%, 99%, 73%, and 95%. Tumor marker sensitivity, specificity, PPV, and NPV were 90%, 46%, 22%, and 96%. MRI and ultrasound concordance was 88%, with sensitivity, specificity, PPV, and NPV of 33%, 99%, 75%, and 94%. MRI sensitivity in ultrasound-discordant cases was 100%. MRI and tumor marker concordance was 88% with sensitivity, specificity, PPV, and NPV of 100%, 86%, 64%, and 100%. MRI specificity in tumor marker-discordant cases was 100%. CONCLUSION: Diagnostic modalities used to assess ovarian neoplasms in pediatric patients typically agree. In cases of disagreement, MRI is more sensitive for malignancy than ultrasound and more specific than tumor markers. Selective use of MRI with preoperative ultrasound and tumor markers may be beneficial when the risk of malignancy is uncertain. CONCISE ABSTRACT: This retrospective review of 1053 patients aged 2-21 years who underwent ovarian mass resection between 2009 and 2021 at 11 pediatric hospitals found that ultrasound, tumor markers, and MRI tend to agree on benign vs malignant, but in cases of disagreement, MRI is more sensitive for malignancy than ultrasound.

Pediatric Surgery Firearm Injury Collaborative Symposium.

Injury from a firearm is now the leading cause of death of children and youth under age 19 in the United States (U.S.) [1] and the incidence of these deaths continues to increase each year [2]. For every death from firearm violence, there are several young people who have been injured by a bullet but not killed. As pediatric surgeons, we are on the front lines of treating these young patients. We have the unforgettable memories of delivering the horrible news to parents in "quiet rooms." [3]. As these injuries fall within our scope of practice, it is incumbent on us as professionals to work to prevent these injuries, apply best practices and work for the best pathways to recovery for our patients who do survive. There is a diverse community of pediatric surgeons tackling this public health problem in a variety of ways [4]. In a pre-meeting symposium at the APSA 2023 Annual meeting, we brought together a community of pediatric surgeons working on this critical area. The following summarizes the presentations of the symposium, with topics including Risk Factors, Injury Prevention, Treatment, Public Initiatives, and National Collaborative Efforts. TYPE OF STUDY: Review Article, Proceedings of a Symposium. LEVEL OF EVIDENCE: 1 through 4 all presented.

Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: A report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5.

BACKGROUND: Patients with stage IV favorable histology Wilms tumor (FHWT) with extrapulmonary metastases (EPM) constitute a small subset of patients with FHWT. Because of their rarity and heterogeneity, optimal FHWT treatment is not well understood. Children's Oncology Group protocol AREN0533 assigned patients with FHWT and EPM to intensified chemotherapy, regimen M, after initial DD-4A chemotherapy. To improve understanding of prognostic factors and best therapies, experiences of patients with EPM on AREN0533, as well as on protocols AREN03B2 and NWTS-5, were reviewed. METHODS: Combined outcomes for patients with EPM from NWTS-5, AREN0533, and AREN03B2 were determined. Those treated on AREN0533 were compared with those treated on NWTS-5. Prognostic factors were explored in the pooled cohort. RESULTS: Forty-seven patients with FHWT with EPM enrolled on AREN0533, 37 enrolled on NWTS-5, and 64 were followed only on AREN03B2. The pooled cohort of all 148 patients demonstrated a 4-year event-free survival (EFS) of 77.3% (95% CI, 70.8-84.4) and 4-year overall survival of 88.9% (95% CI, 83.9-94.2). Four-year EFS of patients with EPM treated on AREN0533 was 76.0% (95% CI, 64.6-89.4) vs 64.9% (95% CI, 51.7-82.2) on NWTS-5; hazard ratio, 0.64, p = .26; no difference in overall survival was observed. Increasing linear age and slow incomplete lung response were associated with worse EFS in a pooled cohort. CONCLUSIONS: Outcomes for patients with EPM are among the lowest for children with FHWT. Further trials with standardized surgical and radiation treatment to metastatic sites, and prospectively collected biologic and treatment details are needed. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov identifiers: NCT00379340, NCT00898365, and NCT00002611.

Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children's Oncology Group AREN18B5-Q.

Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing (n = 85 tumors from 61 patients with matched germline blood DNA), RNA-seq (n = 99 tumors), and DNA methylation analysis (n = 61 peripheral blood, n = 29 non-diseased kidney, n = 99 tumors). We determine the predominant events for bilateral Wilms tumor predisposition: 1)pre-zygotic germline genetic variants readily detectable in blood DNA [WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%), and BRCA-related genes (5%)] or 2)post-zygotic epigenetic hypermethylation at 11p15.5 H19/ICR1 that may require analysis of multiple tissue types for diagnosis. Of 99 total tumor specimens, 16 (16.1%) have 11p15.5 normal retention of imprinting, 25 (25.2%) have 11p15.5 copy neutral loss of heterozygosity, and 58 (58.6%) have 11p15.5 H19/ICR1 epigenetic hypermethylation (loss of imprinting). Here, we ascertain the epigenetic and genetic modes of bilateral Wilms tumor predisposition.

Critical elements of radical nephroureterectomy for pediatric unilateral renal tumor.

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.

Reducing Unnecessary Oophorectomies for Benign Ovarian Neoplasms in Pediatric Patients.

Importance: Although most ovarian masses in children and adolescents are benign, many are managed with oophorectomy, which may be unnecessary and can have lifelong negative effects on health. Objective: To evaluate the ability of a consensus-based preoperative risk stratification algorithm to discriminate between benign and malignant ovarian pathology and decrease unnecessary oophorectomies. Design, Setting, and Participants: Pre/post interventional study of a risk stratification algorithm in patients aged 6 to 21 years undergoing surgery for an ovarian mass in an inpatient setting in 11 children's hospitals in the United States between August 2018 and January 2021, with 1-year follow-up. Intervention: Implementation of a consensus-based, preoperative risk stratification algorithm with 6 months of preintervention assessment, 6 months of intervention adoption, and 18 months of intervention. The intervention adoption cohort was excluded from statistical comparisons. Main Outcomes and Measures: Unnecessary oophorectomies, defined as oophorectomy for a benign ovarian neoplasm based on final pathology or mass resolution. Results: A total of 519 patients with a median age of 15.1 (IQR, 13.0-16.8) years were included in 3 phases: 96 in the preintervention phase (median age, 15.4 [IQR, 13.4-17.2] years; 11.5% non-Hispanic Black; 68.8% non-Hispanic White); 105 in the adoption phase; and 318 in the intervention phase (median age, 15.0 [IQR, 12.9-16.6)] years; 13.8% non-Hispanic Black; 53.5% non-Hispanic White). Benign disease was present in 93 (96.9%) in the preintervention cohort and 298 (93.7%) in the intervention cohort. The percentage of unnecessary oophorectomies decreased from 16.1% (15/93) preintervention to 8.4% (25/298) during the intervention (absolute reduction, 7.7% [95% CI, 0.4%-15.9%]; P = .03). Algorithm test performance for identifying benign lesions in the intervention cohort resulted in a sensitivity of 91.6% (95% CI, 88.5%-94.8%), a specificity of 90.0% (95% CI, 76.9%-100%), a positive predictive value of 99.3% (95% CI, 98.3%-100%), and a negative predictive value of 41.9% (95% CI, 27.1%-56.6%). The proportion of misclassification in the intervention phase (malignant disease treated with ovary-sparing surgery) was 0.7%. Algorithm adherence during the intervention phase was 95.0%, with fidelity of 81.8%. Conclusions and Relevance: Unnecessary oophorectomies decreased with use of a preoperative risk stratification algorithm to identify lesions with a high likelihood of benign pathology that are appropriate for ovary-sparing surgery. Adoption of this algorithm might prevent unnecessary oophorectomy during adolescence and its lifelong consequences. Further studies are needed to determine barriers to algorithm adherence.

Unwrapping Nephrogenic Rests and Nephroblastomatosis for Pediatric Surgeons: A Systematic Review Utilizing the PICO Model by the APSA Cancer Committee.

BACKGROUND: Nephrogenic rests (NR) may represent precursor lesions for Wilms tumor (WT), but their clinical course is not fully understood and no guidelines for treatment exist. This study sought to evaluate the outcomes of pediatric patients with NRs related to traditional chemotherapy and surgery. METHODS: A PRISMA-P-compliant literature search was conducted in MEDLINE, Embase, CINAHL, Web of Science, COCHRANE, and SCOPUS from inception to June 2021. Clinical questions regarding the treatment of NRs, including chemotherapy and surgery, were developed in the population, intervention, comparison, and outcome format. RESULTS: Twenty-five studies including 1445 patients met inclusion criteria for evaluating chemotherapy compared to observation for NRs. Eighteen studies including 1392 patients met inclusion criteria for evaluating the role of surgery for NRs. Patients with isolated NRs who underwent observation progressed to WT 33% of the time; chemotherapy reduced the rate of WT to 3.9%. Observation of multiple NRs and diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) led to progression to WT 50% and 100% of the time, respectively. Chemotherapy reduced the rate of WT to 34% for multiple NRs and 46% for DHPLN. Surgery for isolated NRs reduced the risk of WT development from 23.7% in patients with incomplete excision to 3.3% with complete excision; however, 96% of patients with incompletely excised NRs had bilateral disease. CONCLUSIONS: Observation with close surveillance for isolated NRs is safe. Treatment with chemotherapy is recommended for patients with multiple NRs and DHPLN. Surgical management of NRs should focus on renal function preservation. LEVEL OF EVIDENCE: Treatment study, Level III.

Implications of Immunotherapy for Pediatric Malignancies: A Summary from the APSA Cancer Committee.

Although survival for many pediatric cancers has improved with advances in conventional chemotherapeutic regimens and surgical techniques in the last several decades, it remains a leading cause of disease-related death in children. Outcomes in patients with recurrent, refractory, or metastatic disease are especially poor. Recently, the advent of alternative classes of therapies, including immunotherapies, have revolutionized systemic treatment for pediatric malignancies. Several classes of immunotherapies, including chimeric antigen receptor (CAR) T cell therapy, transgenic T-cell receptor (TCR)-T cell therapy, bispecific T-cell engagers, and monoclonal antibody checkpoint inhibitors have been FDA-approved or entered early-phase clinical trials in children and young adults. The pediatric surgeon is likely to encounter these therapies during the care of children with malignancies and should be familiar with the classes of therapy, indications, adverse events, and potential need for surgical intervention in these cases. This review from the APSA Cancer Committee offers a brief discussion of the three most encountered classes of immunotherapy in children and young adults and discusses surgical relevance. LEVEL OF EVIDENCE: IV.