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Surgical complications remain common in health care and constitute a significant challenge for hospitals, surgeons, and patients. While they cause significant physical, financial, and psychological harm to patients and their families, they also heavily burden the involved physicians. This phenomenon, known as the “second victim,” results in negative short and long-term physical, cognitive, and psychological consequences on the surgeon. In this review, we explored the intricate connections between the surgeons' emotional response to adverse events concerning the patient outcome, perceived peer reaction, and existing social and institutional support systems. Using a selective literature review coupled with personal experiences, we propose a model of this complex interaction and suggest specific interventions to ameliorate the severity of response within this framework. The institution of the proposed interventions may improve the psychological well-being of surgeons facing complications and promote a cultural shift to better support physicians when they occur.

Malignant melanoma is rare in the pediatric population and management is largely extrapolated from adult guidelines. Adult data have shown that immediate completion lymph node dissection (CLND) does not improve overall survival in selected patients with clinically node negative, sentinel lymph node-positive disease. Current nodal management in children is unknown.The National Cancer Database (NCDB) was queried for patients with melanoma from 2012-2017 and patients categorized as pediatric (≤18 years, n=962) or adult (n=327,987). Factors associated with CLND in children with positive SLNB were evaluated in multivariable analysis. Kaplan-Meier survival analysis was performed.Compared to adults, children present with thicker primary tumors (T3 or T4 26.5% vs 15.5%, p0.001), resulting in higher rates of nodal assessment with SLN biopsy or LND (60.2% vs 36.6%, p0.001) and higher rates of regional nodal disease (35.1% vs 23.4%, p0.001). Children underwent higher rates of CLND after SLN biopsy (10.4% vs 4.1%) and upfront lymph node dissection (15.2% vs 8.7%). A decreased rate of CLND was noted in 2017 compared to 2012 (odds ratio (OR) 0.16 (p=0.005). CLND was performed more often on multivariable analysis for older pediatric age (12 years, OR=1.6, p=0.037) and lower extremity primary (OR=0.29, p0.001). Children with regional nodal disease have improved 3-year overall survival compared to adults (96.5% vs 71.0%, p0.001).Children with melanoma have higher rates of nodal disease but better survival than adults. As in adults, there has been a recent increase in close nodal observation rather than CLND for patients with positive SLN. Further study of nodal surveillance for pediatric patients is warranted.

Background Testicular germ cell tumors are uncommon tumors that are encountered by pediatric surgeons and urologists and require a knowledge of appropriate contemporary evaluation and surgical and medical management. Method A review of the recommended diagnostic evaluation and current surgical and medical management of children and adolescents with testicular germ cell tumors based upon recently completed clinical trials was performed and summarized in this article. Results In this summary of childhood and adolescent testicular germ cell tumors, we review the initial clinical evaluation, surgical and medical management, risk stratification, results from recent prospective cooperative group studies, and clinical outcomes. A summary of recently completed clinical trials by pediatric oncology cooperative groups is provided, and best surgical practices are discussed. Conclusions Testicular germ cell tumors in children are rare tumors. International collaborations, data-sharing, and enrollment of patients at all stages and risk classifications into active clinical trials will enhance our knowledge of these rare tumors and most importantly improve outcomes of patients with testicular germ cell tumors. Level of evidence This is a review article of previously published and referenced level 1 and 2 studies, but also includes expert opinion level 5, represented by the American Pediatric Surgical Association Cancer Committee.

Differentiated thyroid carcinomas are rare in young children but represent almost 10% of all malignancies diagnosed in older adolescents. Differentiated thyroid carcinoma in children is more likely to demonstrate nodal involvement and is associated with higher recurrence rates than seen in adults. Decisions regarding extent of surgical resection are based on clinical and radiologic features, cytology, and risk assessment. Total thyroidectomy and compartment-based resection of involved lymph node basins form the cornerstone of treatment. The use of molecular genetics to inform treatment strategies and the use of targeted therapies to unresectable progressive disease is evolving.

Background: Trauma evaluation in the Emergency Department (ED) can be a stressful event for children. With the goal of minimizing pain, anxiety, and unneeded interventions in stable patients, we implemented a Pediatric PAUSE© at our Level 1 Adult/Level 2 Pediatric Trauma Center. The Pediatric PAUSE© is a brief protocol performed after the primary survey, which addresses Pain/Privacy, Anxiety/IV Access, Urinary Catheter/Rectal exam/Genital exam, Support from family or staff, and Explain to patient/Engage with PICU team. The aim was to assess whether performing the PAUSE© interfered with timeliness of emergent imaging in pediatric patients and their disposition. Methods: We identified all patients aged 0-18 years evaluated as trauma activations at our institution after the Pediatric PAUSE© was implemented (10/1/16-3/31/17) as well as two analogous 6-month pre-PAUSE© time periods. Patient demographics, time to imaging studies, and time to ED disposition were analyzed. Findings: One hundred and seventy-two patients met study criteria, with a mean age of 10.9 years and mean Injury Severity Score of 10.6. One hundred fifteen participants (68.5 %) were transferred from other hospitals, and 101 (87.8%) had ≥1 imaging study performed prior to arrival. The Pediatric PAUSE© was performed for 41/163 (25%) study participants. There was no difference in time to first imaging study in participants for whom the PAUSE© was performed (18.4 min vs 15.0 min, p=0.09). Interpretation: The PAUSE© is a practice intervention designed to address the psychosocial needs of pediatric trauma patients and their families to help prevent PTS symptoms. Implementation did not interfere with the timeliness of first imaging in pediatric trauma patients. Funding Statement: The authors state: "No funding to disclose." Declaration of Interests: The authors declare: "No conflicts of interests.' Ethics Approval Statement: The study protocol was approved by the Committee for the Protection of Human Subjects at our institution, granting access to our institution’s existing trauma database and the electronic health records of study patients (Dartmouth College Committee for the Protection of Human Subjections: Study #00030129).

Minimally invasive nephrectomy is performed routinely for adult renal tumors and for many benign pediatric conditions. Although open radical nephroureterectomy remains the standard of care for Wilms tumor and most pediatric renal malignancies, there are an increasing number of reports of minimally invasive surgery (MIS) for those operations as well. The APSA Cancer Committee performed a systematic review to better understand the risks and benefits of MIS in pediatric patients with renal tumors. Methods The search focused on MIS for renal tumors in children and followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist. The initial database search identified 491 published articles, and after progressive review of abstracts and full-length articles, 19 were included in this review. Results There were two direct comparison studies where open surgery and MIS were compared. The remaining studies reported only on minimally invasive nephrectomy. Across all studies, there were a total of 151 patients, 126 of which had Wilms tumor and 10 patients had RCC. 104 patients had MIS, with 47 patients having open surgery. In the two studies in which open surgery and MIS were directly compared, more lymph nodes were harvested during open surgery (median = 2 (MIS) vs 5 (open); mean = 2.47 (MIS) vs 3.8 (open)). Many noncomparison studies reported the harvest of 2 of fewer lymph nodes for Wilms tumor. Several MIS patients were also noted to have intraoperative spill or positive margins. Survival between groups was similar. Conclusions There is a lack of evidence to support MIS for pediatric renal tumors. This review demonstrates that lymph node harvest has been inadequate for MIS pediatric nephrectomy and there appears to be an increased risk for intraoperative spill. Survival data are similar between groups, but follow-up times were inconsistent and patient selection was clearly biased, with only small tumors being selected for MIS. Type of study Review article. Level of evidence III.

Background/Purpose Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults and requires multimodality treatment. The purpose of this review is to present an update on risk stratification as well as surgical and medical management strategies in pediatric rhabdomyosarcoma. Methods A comprehensive review of the current literature on pediatric rhabdomyosarcoma, including the most recent Children's Oncology Group studies and several international collaboratives, was performed by the authors and key findings were summarized in the manuscript. Results FOXO1 fusion status is a stronger prognostic factor than histology and is now used for risk stratification in treatment protocols. For assessment of regional nodal involvement, FDG-PET-CT shows poor sensitivity and specificity to detect histologically confirmed nodal metastasis. Thus, surgical assessment of regional lymph nodes is required for rhabdomyosarcoma of the extremities or trunk as well as paratesticular rhabdomyosarcoma in patients ≥ 10 years of age, although adherence to surgical guidelines remains poor. Hemiscrotectomy performed for scrotal violation in paratesticular rhabdomyosarcoma has not shown an improvement in event free survival and is not recommended. Conclusions Surgical and medical treatment strategies for rhabdomyosarcoma in children continue to evolve. This review provides current evidence-based treatment standards with an emphasis on surgical care. Type of Study Review. Level of Evidence Level IV.

Background To describe a single-institutional experience with an innovative technique using CT-guided injection of autologous blood for localization of nonpleural-based pulmonary nodules prior to thoracoscopic excisional biopsy in pediatric patients. Methods A retrospective review of all patients under the age of 18 with lung lesions suspected to be malignant that were not pleural-based lesions and were not of adequate size to visualize at thoracoscopy, who underwent CT-guided blood tattoo (CGBT) localization between 2006-2019. CGBT was performed under general anesthesia by injecting 0.5-10 mL of autologous blood into the area of the lesions. The patients were then immediately transferred from interventional radiology to the operating room for thoracoscopic excision of the lesion. Demographics, location of lesions, indication for biopsy, and pathology were reviewed. Results In eleven pediatric patients (ages ranging from 4-18 years), preoperative CGBT localization of pulmonary nodules resulted in successful thoracoscopic excisional biopsy. All resections were diagnostic and 82% (9/11 cases) represented a metastatic malignancy as confirmed by pathology. Malignant nodules ranged from 2 to 14 mm in size, while a 13 mm nodule in a patient with history of AML was determined to be an organizing pneumonia and a 12 mm nodule in a second patient revealed a caseating granuloma consistent with Crohn's disease. One patient with a failed attempt at excisional biopsy without preoperative localization then underwent CGBT one week later with successful thoracoscopic excision of the nodule. Conclusions CT-guided blood tattoo is a safe option for localization of nonpleural-based lung nodules prior to thoracoscopic excision in pediatric patients.

Sarcoma can present as locally advanced disease involving pleura for which extra-pleural pneumonectomy (EPP) may be the only surgical option to ensure adequate local control. Data were collected on patients who underwent EPP between January 2009 and August 2021 at Princess Margret Hospital and SickKids (Toronto) using the CanSaRCC (Canadian Sarcoma Research and Clinical Collaboration). Ten patients with locally advanced sarcoma involving the pleura, aged 4 to 59 years (median 19.5 years) underwent EPP. Nine (90%) received pre-operative chemotherapy and eight (80%) achieved an R0 resection. Hemithoracic radiation was administered preoperatively (n = 6, 60%) or postoperatively (n = 4, 40%). Five (50%) patients were alive without disease at last follow-up (median 34.2 months) and time from EPP to last FU was median 29.2 months (range 2.2–87.5). Two patients (20%) had local recurrence, 4.3 and 5.8 months from EPP, and both died from progressive disease, 13.1 and 8.2 months from EPP, respectively. One patient died from brain metastasis (17 months), one died from radiation associated osteosarcoma (66 months), and one died from surgical complications (heart failure from constrictive pericarditis). EPP offers a feasible and life-prolonging surgical consideration for patients with locally advanced sarcoma involving the pleura in combination with chemotherapy and radiation. Consequently, EPP should be considered during multi-disciplinary tumor board discussions at high-volume centers.

ObjectivesPaediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.DesignA multicentre, international, collaborative cohort study.Setting91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.ParticipantsPatients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measureAll-cause mortality at 30 days and 90 days.Results1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (pConclusionsThe COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally.

Rhabdomyosarcoma is the most common pediatric soft tissue sarcoma. Current diagnostic methods involve imaging and tissue biopsy for staging, histology and fusion status assessment. There are presently no serum biomarkers for rhabdomyosarcoma diagnosis or surveillance. Novel approaches and identification of biomarkers are warranted for minimally invasive diagnostic/surveillance techniques. Extracellular vesicles (EVs) are recognized as critical mediators of intercellular communication and the pathophysiology of carcinogenesis and metastasis. This study aimed to characterize the proteome of rhabdomyosarcoma-derived EVs and identify proteomic signatures that correlate with clinical characteristics such as histological subtype, cancer stage, age and metastasis, using patient-derived cell lines. EVs were isolated from cell culture conditioned media by differential ultracentrifugation from four rhabdomyosarcoma cell lines (RH4, RH18, RH30, RD), each in triplicate. Liquid chromatography-tandem mass spectrometry identified EV protein cargo. Proteins identified in our samples were compared to all available EV data in the Vesiclepedia database, using the FunRich software. We identified 1,527 total proteins in our rhabdomyosarcoma-derived EVs. When comparing to Vesiclepedia, 96 unique proteins were identified from our EVs that were not previously annotated in EVs within the database. Expression of these 96 proteins was further evaluated based on clinical characteristics of the tumors the cell lines were derived from. We found a four-protein signature in the EV secretome of rhabdomyosarcoma cell lines correlated with FOXO1 fusion-positive status. This signature includes proteins involved in regulating extracellular matrix organization, regulating gene expression, protein biosynthesis and translation. Rhabdomyosarcoma cells secrete EVs with unique protein cargo based on clinical characteristics of the parent tumor such as histological subtype and FOXO1 fusion status. Further validation of these secreted EV proteins in biological fluids could prove an effective liquid biopsy technique for novel diagnostic approaches or surveillance in pediatric rhabdomyosarcoma. Citation Format: Paula R. Quaglietta, Ashby Kissoondoyal, Ethan Malkin, David Malkin, Reto M. Baertschiger. Proteomic characterization of rhabdomyosarcoma-derived extracellular vesicles reveals a fusion-positive protein signature. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3555.

Background: Hepatoblastoma (HB) is the most frequent liver tumor in children. While most tumors respond well to treatment with good outcomes, there are a subgroup of refractory tumors for which novel therapies are required. Emerging literature has suggested a role of Hsp90 in HB progression. One possible mechanism hypothesizes that Hsp90 helps stabilize misfolded proteins that contribute to HB progression including β-catenin. Our study aimed to investigate if inhibition of Hsp90 would affect the cell viability of hepatoblastoma cell lines in vitro. Methods: Commercially available HEPG2, and patient xenograft-derived hepatoblastoma cell lines (HB214, HB279, and HB303) were analyzed for differences in Hsp90 gene expression by qRTPCR as well as cell viability (n = 3 replicates for each cell line) using the MTS assay. Differences in cell viability for each cell line were further examined after treatment with a 0.1µM or 0.25µM dose of 17-AAG (an HSP90 inhibitor) for 48H. We examined gene expression and the MTS assay cell viability data using linear mixed effects modelling followed by t-tests to examine specific comparisons (significance at p < 0.05). Results: Hsp90 gene expression was significantly increased in HEPG2 cells (p < 0.001) and in HB279 cells (p < 0 .05), but not in HB214, or HB303 cells, compared to HUVECs control cells. Examining clinically relevant characteristics, significant improvements to model fit were found with the inclusion of sex (p < 0.01), β-catenin deletion status (p < 0.01), and a higher PRETEXT stage but not from examining if cell lines were derived from metastatic parent tumors. While we observed no significant cell line viability differences between individual HB cell lines at baseline (0µM 17-AAG treatment) or overall significant differences for treatment with either 0.1µM or 0.25µM dosages of 17-AAG, there were differences in cell viability for individual HB cell lines. We observed significant decreases in cell viability in HEPG2 cells with 0.1µM (p < 0.05) and 0.25µM (p < 0.05), as well as in HB279 cells with 0.1µM (p < 0.05) and 0.25µM (p < 0.05) 17-AAG treatments but observed no effect of 17-AAG treatment on cell viability in HB214, or HB303 cells. Similar improvements in model fit were observed with the inclusion of sex (p < 0.01), β-catenin deletion status (p < 0.01), and a higher PRETEXT stage (p < 0.001), but not from examining if cell lines were derived from metastatic parent tumors. Conclusion: HB cell lines express Hsp90 at levels correlated with age, β-catenin deletion status, and risk stage. Moreover, the expression levels of Hsp90 corresponded to the sensitivity of each cell line to the Hsp90 inhibitor 17-AAG, with cells more highly expressing Hsp90 having a greater reduction in cell viability. Continuing to understand the mechanisms of Hsp90 action in HB, particularly through the previously demonstrated connection with β-catenin, may identify potential targetable therapies in the care of HB. Citation Format: Ashby Kissoondoyal, Emily DeSousa, Paula R. Quaglietta, Emilie Indersie, Stefano Cairo, David Malkin, Lisandro Luques, Reto M. Baertschiger. Reduction in cell viability of hepatoblastoma cells following inhibtion of Hsp90. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3540.

Extracellular vesicles (EVs) are nano-sized (30-1000 nm) membranous particles released by nearly all cell types. EV biology is a rapidly growing field, however its relative novelty and the intrinsic heterogeneity of EVs result in a lack of standardized and reproducible protocols. We sought to develop and validate an EV isolation method using rhabdomyosarcoma cell lines, with multiple characterization/validation methods, to improve the reproducibility and reliability of EV research in pediatric cancer research. EVs were isolated and analyzed in triplicate from 4 rhabdomyosarcoma cell lines (RH4, RH18, RH30, RD), of varying clinical characteristics including subtype, TP53 status and FOXO1 fusion status. Cells were grown to 70% confluency in six 175cm2 flasks, to ensure sufficient EV content for all downstream analyses, then incubated for 48 hours in media containing 10% EV-depleted FBS. The resultant 120mL of conditioned media (CM) per cell line was collected and subject to differential ultracentrifugation to isolate EVs. CM was centrifuged twice, then concentrated to less than 10mL using 3kDa MWCO filter tubes. Concentrated CM was centrifuged twice before passing through a 0.22μm pore-sized syringe filter prior to the final ultracentrifugations. The sample was ultracentrifuged and the EV pellet was carefully washed, re-centrifuged and resuspended in 100μL of PBS. Protein analysis by Western blot confirmed the presence of EV markers (syntenin-1, TSG101) and absence of non-EV markers (calnexin, histone H2Ax). EV quantification and size distributions were evaluated by NanoSight nanoparticle tracking analysis and visualized by transmission electron microscopy. All isolations were positive for EV markers and negative for non-EV markers by Western Blotting. All isolations showed similar size distributions by nanoparticle tracking analysis, within the range of 30-250nm. EVs in each sample with the typical cup-like shape were observed in electron microscope images of EVs. Overall, our method demonstrates good reproducibility of EV isolations from multiple rhabdomyosarcoma cell lines. This methodology can be used as a baseline for other cell lines to provide greater consensus within the field, allowing further discoveries analyzing the secretome of patient-derived cell lines with the potential to translate into more specific diagnostic tools. Citation Format: Paula R. Quaglietta, Ashby Kissoondoyal, Ethan Malkin, Salvador Mejia, Ann Gong, David Malkin, Reto M. Baertschiger. Isolation and validation of small extracellular vesicles from rhabdomyosarcoma cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5309.

Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis.A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse.In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α-fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P.001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P.001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P.001). Disease-free status at any point predicted survival.This multi-institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk-stratified algorithms for children with HCC.This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.

Pulmonary nodules that are deep within lung parenchyma and/or small in size can be challenging to localize for biopsy. This study describes current trends in performance of image-guided localization techniques for pulmonary nodules in pediatric patients.A retrospective review was performed on patients 21 years of age undergoing localization of pulmonary nodules at 15 institutions. Localization and resection success, time in interventional radiology (IR), operating room (OR) and total anesthesia time, complications, and technical problems were compared between techniques.225 patients were included with an average of 1.3 lesions (range 1-5). Median nodule size and depth were 4 mm (range 0-30) and 5.4 mm (0-61), respectively. The most common localization techniques were: wire + methylene blue dye (MBD) (28%), MBD only (25%), wire only (14%), technetium-99 only (11%), coil + MBD (7%) and coil only (5%). Localization technique was associated with institution (p 0.01); technique and institution were significantly associated with mean IR, OR, and anesthesia time (all p 0.05). Comparing techniques, there was no difference in successful IR localization (range 92-100%, p = 0.75), successful resection (94-100%, p = 0.98), IR technical problems (p = 0.22), or operative complications (p = 0.16).Many IR localization techniques for small pulmonary nodules in children can be successful, but there is wide variability in application by institution and in procedure time.Retrospective review, Level 3.

IntroductionChildhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.MethodsProspective cohort study in 109 institutions in 41 countries. Inclusion criteria: children ResultsAll-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3–11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); pConclusionsChildren with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer.

OBJECTIVE To describe utilization and long-term outcomes of pneumonectomy in children and adolescents with cancer. SUMMARY BACKGROUND DATA Pneumonectomy in adults is associated with significant morbidity and mortality. Little is known about the indications and outcomes of pneumonectomy for pediatric tumors. METHODS The Pediatric Surgical Oncology Research Collaborative (PSORC) identified pediatric patients

Background/Purpose Cancer predisposition syndromes (CPS) are a heterogeneous group of inherited disorders that greatly increase the risk of developing malignancies. CPS are particularly relevant to pediatric surgeons since nearly 10% of cancer diagnoses are due to inherited genetic traits, and CPS often contribute to cancer development during childhood. Materials/Methods The English language literature was searched for manuscripts, practice guidelines, and society statements on “cancer predisposition syndromes in children”. Following review of these manuscripts and cross-referencing of their bibliographies, tables were created to summarize findings of the most common CPS associated with surgically treated pediatric solid malignancies. Results Pediatric surgeons should be aware of CPS as the identification of one of these syndromes can completely change the management of certain tumors, such as WT. The most common CPS associated with pediatric solid malignancies are outlined, with an emphasis on those most often encountered by pediatric surgeons: neuroblastoma, Wilms’ tumor, hepatoblastoma, and medullary thyroid cancer. Frequently associated non-tumor manifestations of these CPS are also included as a guide to increase surgeon awareness. Screening and management guidelines are outlined, and published genetic testing and counseling guidelines are included where available. Conclusion Pediatric surgeons play an important role as surgical oncologists and are often the first point of contact for children with solid tumors. In their role of delivering a diagnosis and developing a follow-up and treatment plan as part of a multidisciplinary team, familiarity with common CPS will ensure evidence-based practices are followed, including important principles such as organ preservation and intensified surveillance plans. This review defines and summarizes the CPS associated with common childhood solid tumors encountered by the pediatric surgeon, as well as common non-cancerous disease stigmata that may help guide diagnosis. Type of study Summary paper. Level of evidence 5.

Branchial arch and cleft anomalies are congenital malformation of the first, second, third and fourth branchial arch and most frequently present as cysts, sinuses or fistulae in the auricular, mandibular or cervical areas. Good knowledge of embryological development helps to understand the anatomy and relationships of branchial anomalies with surrounding structures, especially the laryngeal nerves (superior and recurrent) and vascular structures. Diagnostic work up includes a good physical exam, ultrasonographical evaluation as well as MRI for cross-sectional imaging in more complicated cases. Fistulogram and endoscopy can also be helpful, especially in third and fourth branchial cleft anomalies. Surgical excision is usually the treatment of choice, on an elective basis. If the cervical cyst, sinus or fistula are infected, incision and drainage and antibiotic treatment are recommended, followed by elective excision when the inflammation has resolved.

A previously well 4-month-old boy, with no history suggestive of immunodeficiency, presented to the clinic with a 1-month history of a right-sided inguinal mass ([Figure 1][1]). He was a twin pregnancy born at 37 weeks’ gestational age to a healthy mother of Canadian origin who was living in

Objectives To evaluate the rate of surgical procedures, anesthetic use, and imaging studies by prematurity status for the first year of life we analyzed data for Texas Medicaid-insured newborns. Study design We developed a retrospective population-based live birth cohort of newborn infants insured by Texas Medicaid in 2010-2014 with 4 subcohorts: extremely premature, very premature, moderate/late premature, and term. Results In 1 102 958 infants, surgical procedures per 100 infants were 135.9 for extremely premature, 35.4 for very premature, 15.5 for moderate/late premature, and 6.5 for term. Anesthetic use was 62.0 for extremely premature, 20.8 for very premature, 11.1 for moderate/late premature, and 5.6 for the term subcohort. The most common procedures in the extremely premature were neurosurgery, intubations, and procedures that facilitated caloric intake (gastrostomy tubes and fundoplications). The annual rates for the first year of life for chest radiograph ranged from 15.0 per year for the extremely premature cohort to 0.6 for term infants and for magnetic resonance imaging (MRI) from 0.3 to 0.01. MRI was the most common imaging study with anesthesia support in all maturity levels. MRIs were done in extremely premature without anesthesia in over 90% and in term infants in 57.2%. Conclusions Surgical procedures, anesthetic use, and imaging studies in infants are common and more frequent with higher a degree of prematurity while the use of anesthesia is lower in more premature newborns. These findings can provide direction for outcome studies of surgery and anesthesia exposure.

This article reviews of the current evidence-based treatment standards for children with Wilms tumor. In this article, a summary of recently completed clinical trials by the Children’s Oncology Group are provided, the current diagnostic evaluation and surgical standards are discussed, and the surgical impact on current risk stratification for patients with Wilms tumor is highlighted. LEVEL OF EVIDENCE: This is a review article of previously published and referenced LEVEL 1 studies, but also includes expert opinion LEVEL V, represented by the American Pediatric Surgical Association Cancer Committee.

Background/purpose Lymphadenopathy is a common complaint in children. Pediatric surgeons are often called upon to evaluate, treat, and/or biopsy enlarged lymph nodes. With many nonsurgical causes in the differential diagnosis, the surgeon plays the important role of providing reassurance and timely diagnosis while minimizing the pain and morbidity associated with surgical interventions in children. The purpose of this summary paper is to provide a management guide for surgeons working up children with lymphadenopathy. Materials/methods The English language literature was searched for “lymphadenopathy in children”. All manuscript types were considered for review, regardless of medical specialty, with emphasis placed on published guidelines, algorithms, and reviews. After thorough review of these manuscripts and cross-referencing of their bibliographies, the attached algorithm was developed, with emphasis on the role and timing of surgical intervention. Results The APSA Cancer Committee developed the attached algorithm to fill a gap in the surgical literature. It outlines lymphadenopathy workup and treatment with emphasis on the role and timing of surgical intervention. Conclusion This review defines and summarizes the common etiologies and presentations of lymphadenopathy in children, and offers a straightforward algorithm for evaluation of and treatment with an emphasis on malignancy risk and surgical management. Type of study Summary paper. Level of evidence Level V.

Introduction Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms that arise in the gastrointestinal tract. While most GISTs are driven by mutations in cKIT or PDGFR, approximately 10% lack these variants and are referred to as ‘wild-type’. Wild-type GISTs are commonly succinate dehydrogenase (SDH)-deficient and are characterized by indolent, multi-focal disease at presentation. On occasion, patients experience symptomatic disease progression warranting treatment ; imatinib or sunitinib offer minimal benefit. PIK3CA mutations have recently been described in a small proportion of GIST. Case report A previously healthy 16-year-old female presented with a five-month history of vomiting and weight loss, compatible with gastric outlet obstruction. Computerized tomography demonstrated a large gastric mass, and multiple liver and peritoneal metastases. Biopsy showed nests of epithelioid cells with round nuclei, vesicular chromatin, and eosinophilic cytoplasm. The lesional cells were immunoreactive for CD117, DOG1, CD34, and smooth muscle actin, while negative for SDH-B immunohistochemistry, in keeping with SDH-deficient GIST. Germline and somatic panel sequencing were performed through the SickKids Cancer Sequencing Program along with RNA sequencing by Illumina TruSight RNA Pan-Cancer NGS analysis. Somatic analysis revealed a PIK3CA p.Glu545Lys (E545K) mutation at 0.12 variant allele fraction (VAF). The patient was also found to have germline heterozygous pathogenic splice variant in the SDHB gene c.75+1 G>T (p?). In the light of the molecular findings and no alternative curative options, compassionate access to alpelisib was sought. The patient started drug at the recommended adult dose of 300 mg by mouth daily, and after completing two 28-day cycles, showed marked improvement in her abdominal distension and discomfort. Her appetite improved with documented nutritional weight gain. Reimaging at this time showed a 20% reduction in the sum of maximum dimensions of target lesions (per RECIST 1.1). Repeat imaging after five months on treatment confirmed continued improvement with 25% reduction compared to baseline.The patient did not experience hypersensitivity, severe cutaneous adverse reactions, hyperglycemia or pneumonitis. She currently continues on alpelisib monotherapy. Conclusion We describe the first report of a clinically meaningful response to a PIK3CA inhibitor in an adolescent patient with advanced metastatic SDH-deficient GIST harbouring a somatic activating PIK3CA hotspot mutation. There is still much to be learned about the biology of pediatric/wild-type GIST. In these rare cases, we recommend referral to specialized centers and incorporation of comprehensive next generation sequencing into care. Sequencing should be performed both on germline and somatic DNA to evaluate for a cancer predisposition syndrome, along with possible druggable targets in PIK3CA, cKIT or PDGFRA. We believe that the lack of routine comprehensive genomic analysis may underestimate the frequency of such rare variants. Citation Format: Sarah Cohen-Gogo, Nisha Kanwar, Furqan Shaikh, Reto M. Baertschiger, Adam Shlien, David Malkin, Juan Putra, Ailish Coblentz, Anita Villani, Abha A. Gupta, Daniel A. Morgenstern. Response to alpelisib in an adolescent with PIK3CA-mutated metastatic gastrointestinal stromal tumour [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P136.

Objective Unintentional window falls represent a preventable source of injury and death in children. Despite major campaigns in some larger cities, there continue to be unintentional falls from windows throughout the United States. We aimed to identify risk factors and trends in unintentional window falls in the pediatric population in a national and regional sample. Methods A retrospective analysis of annual emergency department (ED) visits from the National Electronic Injury Surveillance System using product codes specific to windows, as well as patient encounters for unintentional window falls from January 2007 to August 2017 using site-specific trauma registries from 10 tertiary care children's hospitals in New England. National and state-specific census population estimates were used to compute rates per 100,000 population. Results There were 38,840 ED visits and 496 regional patients who unintentionally fell from a window across the study period between 0 and 17 years old. The majority of falls occurred in children under the age of 6 and were related to falls from a second story or below. A decreased trend in national ED visits was seen, but no change in rates over time for regional trauma center encounters. A high number of falls was found to occur in smaller cities surrounding metropolitan areas and from single family residences. Conclusions Falls from windows represent a low proportion of overall types of unintentional sources of injury in children but are a high risk for severe disability. These results provide updated epidemiologic data for targeted intervention programs, as well as raise awareness for continued education and advocacy.

Background Differentiated thyroid carcinomas (DTCs) are rare in young children but represent almost 10% of all malignancies diagnosed in older adolescents. Methods This article reviews the recent literature describing surgical therapeutic approaches to pediatric DTC, associated complications, and long-term recurrence and survival outcomes. Results Similar to adult thyroid cancers, pediatric DTCs are more common in females and are associated with thyroid nodules, family history of thyroid cancer, radiation exposure, iodine deficiency, autoimmune thyroid disease, and genetic syndromes. Management of thyroid cancers in children involves ultrasound imaging, fine needle aspiration, and surgical resection with treatment decisions based on clinical and radiological features, cytology and risk assessment. Conclusions Total thyroidectomy and compartment based resection of clinically involved lymph node basins form the cornerstone of treatment of DTC. There is an evolving literature regarding the use of molecular genetics to inform treatment strategies and the use of targeted therapies to treat iodine refractory and surgically unresectable progressive disease. Type of study Summary review. Level of evidence This is a review article of previously published Level 1–5 articles that includes expert opinion (Level 5).

BACKGROUND Identification and development of young investigators (YI) is critical to the long-term success of research organizations. In 2004, the Children's Oncology Group (COG) created a mentorship program to foster the career development of YIs (faculty

BACKGROUND: Optimal management of neutropenic appendicitis (NA) in children undergoing cancer therapy remains undefined. Management strategies include upfront appendectomy or initial nonoperative management. We aimed to characterize the effect of management strategy on complications and length of stay (LOS) and describe implications for chemotherapy delay or alteration. METHODS: Sites from the Pediatric Surgery Oncology Research Collaborative performed a retrospective review of children with NA over a 6-year period. RESULTS: Sixty-six children, with a median age of 11 years (range 1–17), were identified with NA while undergoing cancer treatment. The most common cancer diagnoses were leukemia (62%) and brain tumor (12%). Upfront appendectomy was performed in 41% of patients; the remainder had initial nonoperative management. Rates of abscess or perforation at diagnosis were equivalent in the groups (30% vs 24%; P = .23). Of patients who had initial nonoperative management, 46% (17 of 37) underwent delayed appendectomy during the same hospitalization. Delayed appendectomy was due to failure of initial nonoperative management in 65% (n = 11) and count recovery in 35% (n = 6). Cancer therapy was delayed in 35% (n = 23). Initial nonoperative management was associated with a delay in cancer treatment (46% vs. 22%, P = .05) and longer LOS (29 vs 12 days; P = .01). Patients who had initial nonoperative management and delayed appendectomy had a higher rate of postoperative complications (P CONCLUSIONS: In pediatric patients with NA from oncologic treatment, upfront appendectomy resulted in lower complication rates, reduced LOS, and fewer alterations in chemotherapy regimens compared to initial nonoperative management.

Introduction The shortage of medical doctors in certain geographies and certain disciplines, resident work hour limitations and the demonstrated positive impact of advanced providers (nurse practitioners, physician assistants and clinical nurse specialists) on the quality and efficiency of care in numerous specialties have led to broader integration of advanced providers in healthcare organizations. With regard to pediatric surgery, some tertiary centers have successfully implemented 24/7 nurse practitioner coverage for their inpatient services. However, pediatric surgery practices vary throughout North America and the broader presence and function of advanced providers among all practice types and settings has not been characterized previously. The purpose of this survey is to conduct a descriptive evaluation of current pediatric surgical practices in North America with regard to advanced provider coverage and their perceived impact on care delivery and patient satisfaction. Methods A 14-item online survey, approved by the American Pediatric Surgical Association (APSA) Outcomes and Evidence-Based Practice Committee, was distributed to all full APSA members (N = 1189, opening rate of 56%), representing the vast majority of pediatric surgeons in North America. The survey investigated the practice characteristics of the responding surgeon, the presence and role of advanced providers in their practice and their perceived impact on patient care. Descriptive statistics were performed to characterize the function of advanced providers in pediatric surgery practices. Further analysis was performed to assess for geographic differences in staffing practices using United States Census Divisions. Results A total of 266 pediatric surgeons completed the survey (response rate 22% and 40% considering “email send out” and “email opening” rates respectively), with 47.6% employed at free standing children's hospitals and 41.1% employed at a children's hospital within an adult hospital. Nearly all respondents (N = 244, 91.7%) reported the presence of advanced providers in their practice with nurse practitioners (N = 216) and physician assistants (N = 101) most commonly represented. The majority of advanced providers (N = 189, 77.8%) covered both general surgery and trauma patients. Advanced providers worked nearly equally in the outpatient (N = 219, 89.8%) and inpatient setting (N = 232, 95.1%), though less often in the neonatal (N = 131) or pediatric (N = 126) intensive care unit. Fifteen percent of surgeons (N = 40) reported that advanced providers provided 24/7 coverage within their surgical practice. Surgeons reported that advanced providers had a very positive (75%) or positive (21%) impact on their clinical practice, with none reporting a negative impact. Surgeons also reported that advanced providers had a very positive (74%) or positive (21%) impact on perceived patient satisfaction. The main area in which surgeons reported the most significant impact of associate providers was continuity of care (N = 77), efficiency of service (N = 66) and education of parents and patients (N = 53). Conclusion Pediatric surgical practices of all types are broadly utilizing advanced providers. Surgeons report that the integration of advanced providers across inpatient and outpatient settings has positively impacted care, advancing both continuity of care and efficiency of service. Advanced providers likely represent part of the solution to delivering quality care in current delivery systems. Study Type Prospective Study/ Survey Level of Evidence IV

We present a rare case of a newborn with H-type tracheoesophageal fistula (TEF) who developed pyloric stenosis postoperatively, 10 days after he was started on erythromycin to promote gastric emptying. We report this case to describe the relationship between H-type TEF repair, erythromycin therapy, and the development of infantile hypertrophic pyloric stenosis.

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.

Embryonic stem cells (ESC) can differentiate into all cell lineages, and ESC-like cells were shown to induce hematopoietic chimerism and tolerance in allogeneic models. The aim of our study was to test the capacity of mouse ESC (mESC) to engraft in rats in a xenotransplantation setting. Forty-six rats were transplanted intravenously with 1 million mESC, without immunosuppression (group 1, n = 23) or with cyclosporine (group 2, n = 23). Three months after mESC transplantation, skin grafts were performed from allogeneic, xenogeneic identical to mESC, or xenogeneic third party donors. At day 27 post-transplant, we detected circulating mouse cells in the blood of 4/23 and 5/23 animals of group 1 and group 2, respectively. Chimerism was confirmed by PCR. We also identified long-term surviving murine cells within livers of chimeric animals. Skin grafts showed no difference in survival between allogeneic and xenogeneic donors. Transplantation of xenogeneic mouse ESC induced short-term chimerism in the blood and persistent tissue chimerism in the liver of recipient rats, but did not induce tolerance to skin grafts. Improved immunosuppressive protocols should be tested to prolong chimerism and allow tolerance.

PURPOSE OF REVIEW: Organ preservation aims at reducing ischemia-reperfusion injury and maintains or even improves its function, and, therefore, increases transplant safety and efficiency. With the chronic lack of organs for transplantation, marginal donors are more and more frequently used in Western countries. New challenges, therefore, have to be met in organ preservation. RECENT FINDINGS: We summarize the effects of cold preservation on various organ grafts, with particular emphasis on the pancreas. We review the different preservation solutions currently available in the clinic, and we present the current knowledge and clinical experience in pancreas and islet transplantation. SUMMARY: Overall, in whole pancreas and islet transplantation, current cold preservation solutions (University of Wisconsin solution, Celsior, histidine-tryptophan-ketoglutarate) seem to be equivalent, with only few studies showing better results with University of Wisconsin solution. Regarding preservation with the two-layer method, conflicting results have been reported, and proper prospective controlled studies have yet to be performed to gather evidence on its impact on islet yield and function. Some recent developments and future strategies in general organ preservation not yet applied to pancreas preservation are reviewed at the end of the article.