Neuroblastoma, a deadly pediatric cancer derived from sympathetic ganglia of the peripheral nervous system, frequently metastasizes, driving poor outcomes. Primary neuroblastomas are well-characterized, but the mechanisms underlying metastasis remain poorly understood. Here, by applying single-cell and spatial multi-omics analyses to primary and metastatic tumors, we found that lymph-node metastases in high-risk neuroblastomas display distinctive cellular heterogeneity and plasticity, marked by mesenchymal-like and stem-like states and heightened epithelial-to-mesenchymal transition activity compared to primary adrenal tumors. Additionally, compared to primary adrenal masses, the metastatic niche display increased immunosuppressive myeloid programs, heightened immune checkpoint signaling, and lymphocyte exhaustion, which are indicative of immune evasion and dysfunction. Notably, metastatic neuroblastomas show elevated eIF4F translation machinery and XPO1 levels. Dual inhibition of eIF4A and XPO1 synergistically halted tumor growth and prolonged survival in xenograft models. Together, our multi-omics studies reveal the molecular and cellular plasticity that contributes to therapy resistance and highlight exploitable therapeutic vulnerabilities in high-risk metastatic neuroblastomas.

The International Network on Esophageal Atresia (INoEA) stands as a beacon of collaboration in addressing the complexities of this congenital condition on a global scale. The eleven board members, from various countries (USA, Canada, France, Australia, Italy, Sweden, Germany, and The Netherlands) and backgrounds (pediatric gastroenterology, pediatric surgery, pediatric pulmonology, nursing, and parents) met in a face-to-face symposium in Lille in November 2023, to identify challenges and solutions for improving global collaboration of the network.

Objective: This paper aims to evaluate the pediatric surgery training pipeline vis-à-vis the pediatric surgery match and operative experience of pediatric surgery fellows. Summary of Background Data: Pediatric surgery remains a competitive surgical subspecialty. However, there is concern that operative experience for pediatric surgery fellows is changing. This paper examines the selectivity of the pediatric surgery match, along with the operative experience of pediatric surgery fellows to characterize the state of pediatric surgery training. Methods: The pediatric surgery fellowship match was analyzed from the National Resident Matching Program data from 2010 to 2019. Selectivity among fellowships was compared using analysis of variance with Dunnett test. Operative log data for pediatric fellows was analyzed using the Accreditation Council for Graduate Medical Education case logs from 2009 to 2019. Linear regression analysis was used to evaluate trends in operative volume over time. Results: Pediatric surgery had the highest proportion of unmatched applicants (47.2% ± 5.3%) and lowest proportion of unfilled positions (1.4% ± 1.6%) when compared to other National Resident Matching Program surgical fellowships. Accreditation Council for Graduate Medical Education case log analysis revealed a statistically significant decrease in cases for graduating fellows (–5.3 cases/year, P < 0.05). Total index cases decreased (–4.7 cases/year, P < 0.01, R2 = 0.83) such that graduates in 2019 completed 59 fewer index operations than graduates in 2009. Conclusion: Although pediatric surgery fellowship remains highly selective there has been a decline in the operative experience for graduating fellows. This highlights the need for evaluation of training paradigms and operative exposure in pediatric surgery to ensure the training of competent pediatric surgeons.

Children less than 5 years old are at high risk for foreign body ingestion or aspiration. Therefore, identifying workup and management principles of foreign body ingestion, in the pediatric population, is necessary for pediatric practitioners. Differentiation of caustic ingestion versus benign ingestion is necessary to determine urgency of management. Plain film X ray imaging can be used to differentiate a button battery versus a coin ingestion, based on the halo sign. The urgency of battery ingestion requires immediate medical attention and endoscopic removal, however treatment with honey during transport may improve outcomes. Perforation can occur via caustic ingestion, sometimes with a delayed presentation. However, the most common cause of esophageal perforation is iatrogenic. In many cases perforation can be managed non operatively if contained and adequately drained.

Consolidation using high-dose chemotherapy with autologous stem cell transplantation (ASCT) is an important component of frontline therapy for children with high-risk neuroblastoma. The optimal preparative regimen is uncertain, although recent data support a role for busulfan/melphalan (BuMel). The Children's Oncology Group (COG) conducted a trial (ANBL12P1) to assess the tolerability and feasibility of BuMel ASCT following a COG induction. Patients with newly diagnosed high-risk neuroblastoma who did not progress during induction therapy and met organ function requirements received i.v. busulfan (every 24 hours for 4 doses based on age and weight) and melphalan (140 mg/m(2) for 1 dose), followed by ASCT. Busulfan doses were adjusted to achieve to an average daily area under the curve (AUC) <5500 mu M x minute. The primary endpoint was the occurrence of severe sinusoidal obstruction syndrome (SOS) or grade >= 4 pulmonary complications within the first 28 days after completion of consolidation therapy. A total of 146 eligible patients were enrolled, of whom 101 underwent BuMel ASCT. The overall incidence of protocol-defined unacceptable toxicity during consolidation was 6.9% (7 of 101). Six patients (5.9%) developed SOS, with 4 (4%) meeting the criteria for severe SOS. An additional 3 patients (3%) experienced grade >= 4 pulmonary complications during consolidation. The median busulfan AUC was 4558 mu M x min (range, 3462 to 5189 x minute) for patients with SOS and 3512 mu M x min (2360 to 5455 mu M x minute) (P = .0142). No patients died during consolidation. From the time of study enrollment, the mean 3-year event-free survival for all 146 eligible patients was 55.6 +/- 4.2%, and the mean 3-year overall survival was 74.5 +/- 3.7%. The BuMel myeloablative regimen following COG induction was well tolerated, with acceptable pulmonary and hepatic toxicity. (C) 2021 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.

Objectives/HypothesisRepair of large, recurrent, and complex tracheoesophageal fistulas (TEFs) is challenging and numerous different surgical approaches exist. These various techniques each carry a set of risks and possible complications such as fistula recurrence, tracheal stenosis or pouches, esophageal stenosis, and recurrent laryngeal nerve injury. Slide tracheoplasty is a reconstructive technique successfully used in many different airway pathologies, including TEF repair. This study examines the success, limits, and complications related to slide tracheoplasty for repair of complex TEFs.Study DesignRetrospective chart review.MethodsPatients undergoing TEF repair using a cervical or thoracic approach slide tracheoplasty, at a single institution, between July 2008 and December 2019 were retrospectively reviewed. Demographic data, comorbidities, TEF etiology and surgical history, slide tracheoplasty details and outcomes, and postoperative complication data were examined using descriptive statistics.ResultsTwenty‐six patients underwent 27 slide tracheoplasties for TEF (20 cervical approaches, 7 thoracic approaches) with a mean age of 5.2 years (IQR 0.7–7.6) at time of surgery. The most common TEF etiologies included congenital (n = 13), tracheostomy tube erosion (n = 5), and button battery ingestion (n = 4). Fistulas ranged in size from <0.5 mm to 4 cm and 59% had previous endoscopic or open repairs. There were two TEF recurrences (7.4%), one of which was successfully revised and the other which was treated with stent placement. Postoperative complications included dehiscence (3.7%), unilateral vocal fold paralysis (3.7%), and mild tracheal stenosis (18.5%).ConclusionsSlide tracheoplasty is an effective surgical technique for treating complex congenital and acquired TEFs with lower rates of complications when compared to other techniques.Level of Evidence4 Laryngoscope, 132:1542–1547, 2022

The wide spectrum of ovarian lesions in infants and children and rarity of some tumors can present a challenge for diagnosis and management. Management approaches must take into account the differences between pediatric and adult tumors. In children, the distribution of tumor types is markedly different; tumors often present at a less advanced stage, and most have a more favorable natural history and response to therapy. Advances in imaging techniques over a decade have led to earlier and more common detection of non-neoplastic lesions, while progress in biochemical, immunohistology, and cytogenetic technology has resulted in more readily diagnosed neoplastic lesions. Surgical staging with histologic confirmation must be done to supplement the clinical assessment of disease status, and precise staging is based on clinical examination, surgical exploration, tissue histology, and fluid cytology. Staging of epithelial ovarian cancer is performed at the time of surgery using the International Federation of Gynecology and Obstetrics (FIGO) staging system. Pediatric germ cell tumors are staged according to the system established by the Children’s Oncology Group (COG). The uncommon nature of ovarian neoplasms increases the value of evaluation and treatment protocols developed from multi-institutional collaborative studies. The overall goal of surgery in children is to evaluate the extent of disease, completely resect the tumor, and spare all uninvolved reproductive organs. Preservation of reproductive potential is a high priority. Laparoscopic procedures confer benefits including shorter recovery time and briefer hospital stays when indicated and done by experienced surgeons. This chapter will focus mainly on the diagnosis and management of the most frequently seen neoplastic ovarian lesions in children.

Introduction: The perioperative environment is one of the most complex areas within a hospital with significant safety risks. Despite a long history of safety-focused work, a recent cluster of patient safety events prompted a renewed comprehensive approach to improve safety processes and transform culture. Methods: Our team comprehensively approached perioperative safety through integration across traditional silos and a focus on institutional safety culture. This approach consisted of a careful review of all events, developing Perioperative Safety Coordinating and Education teams, testing and implementing new/revised safety processes, and an ongoing evaluation plan. Results: Updates to our Perioperative Safety Mission and Tenets and the development of an empowered Safety Culture Champion team composed of a diverse group of frontline team members addressed our safety culture. In addition, key safety processes (time-outs, intraoperative huddles, and prevention of retained foreign bodies) were revised and implemented. Observation of key safety processes demonstrates a 90% compliance, which includes all steps and team engagement. After implementation, a span of 377 days between events was accomplished, which is significantly higher than the 33 days between events during our cluster. Conclusions: This work builds upon prior incremental improvements through a comprehensive investment in not only improving key processes but transforming the safety culture. Acceptable deviance from the standard process is no longer the norm. Instead, an approach that emphasizes understanding, integration, engagement, and accountability for safety by each team member for every patient, every time, every day, has been implemented.

The evolution of the treatment of pediatric solid tumors has been one of progressive improvements in survival. With the advent of pediatric cooperative groups, a systematic approach has brought integrated multidisciplinary care to childhood cancer patients. Improved medical regimens and advances in the basic understanding and characterization of molecular biology of individual tumors continues to bring new treatment options. As long term survival has improved, a greater appreciation of the late effects of treatment has led to increase awareness and intervention for things like infertility. The surgeon remains a critical member of the treatment team. Surgical treatment techniques continue to evolve and the role of surgery in each tumor type is continually redefined. It is incumbent on the treating surgeon to know the treatment guidelines for each case in order to provide the patient with the best opportunity for a successful outcome.

Purpose Neuroblastoma is the most common extracranial solid pediatric malignancy, with poor outcomes in high-risk disease. Standard treatment approaches employ an increasing array of aggressive multimodal therapies, of which local control with surgery and radiotherapy remains a backbone; however, the benefit of broad regional nodal irradiation remains controversial. We analyzed centrally reviewed radiation therapy data from patients enrolled on COG A3973 to evaluate the impact of primary site irradiation and the extent of regional nodal coverage stratified by extent of surgical resection. Methods Three hundred thirty high-risk neuroblastoma patients with centrally reviewed radiotherapy plans were analyzed. Outcome was evaluated by the extent of nodal irradiation. For the 171 patients who also underwent surgery (centrally reviewed), outcome was likewise analyzed according to the extent of resection. Overall survival (OS), event-free survival (EFS), and cumulative incidence of local progression (CILP) were examined by Kaplan-Meier, log-rank test (EFS, OS), and Grey test (CILP). Results The five-year CILP, EFS, and OS for all 330 patients receiving radiotherapy on A3973 were 8.5% +/- 1.5%, 47.2% +/- 3.0%, and 59.7% +/- 3.0%, respectively. There were no significant differences in outcomes based on the extent of lymph node irradiation regardless of the degree of surgical resection (< 90% or >= 90%). Conclusion Although local control remains a significant component of treatment of high-risk neuroblastoma, our results suggest there is no benefit of extensive lymph node irradiation, irrespective of the extent of surgical resection preceding stem cell transplant.

Purpose of Review As imaging technologies expand to include image-guided anatomical navigation and surgical techniques evolve to accommodate increasingly complex interventions with minimally invasive approaches, interventionalists and surgeons have convened in a novel area of hospitals around the world, the hybrid operating room. Although these assets have long been used for cardiovascular procedures, the integration of these tools in a designated surgery suite has given rise to a variety of novel interventions and multi-specialty collaborations. Recent Findings In this review, we highlight current international hybrid room experiences in many fields, spanning from neurosurgery to urology. We also comment on our institutional journey of surgery-interventional radiology collaborations in developing our image-guided surgery program for a pediatric population. Summary As the hybrid operating room continues to gain traction globally, surgeons and interventional radiologists’ creativity and collaborative problem-solving skills will continue to be pushed to improve patient care. Identifying practice gaps and collaborating with industry is vital for further refinement of these tools.

Background: The conventional paradigm that all children with appendicitis require an appendectomy is being challenged by the idea that some patients may be successfully managed non-operatively. The study aimed to determine if matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) are candidate biomarkers for estimating the probability of complicated appendicitis in pediatric patients. Methods: The study was a single-institution, prospective cohort study. MMP and TIMP serum protein concentrations were measured in patients with suspected appendicitis. Three hundred and thirty-one patients were enrolled with appendicitis. Classification and Regression Tree (CART) analysis was used to determine the combination of candidate biomarkers that best predicted complicated appendicitis. Results: The CART-generated decision tree for the derivation cohort included WBC count, MMP-8, MMP-9, MMP12, TIMP-2, and TIMP-4 and had the following test characteristics for estimating the probability of complicated appendicitis (95% CI): AUC 0.86 (0.81-0.90); sensitivity 91% (83-96); specificity 61% (53-68); positive predictive value 58% (50-66); negative predictive value 92% (84-96); positive likelihood ratio (LR) 2.3 (1.9-2.8); and negative LR 0.15 (0.08-0.3). Conclusions: MMPs and TIMPs have the potential to serve as biomarkers to estimate the probability of complicated appendicitis in pediatric patients. The multi-biomarker-based decision tree has test characteristics suggesting clinical utility for decision making. Published by Elsevier Inc.

Background: Tracheoinalacia is the most common congenital abnormality of the trachea. Posterior tracheopexy to alleviate posterior intrusion contributing to dynamic tracheal collapse has been reported using thoracotomy or median stemotomy. Here we describe the minimally invasive operative technique of thoracoscopic posterior tracheopexy with bronchoscopic guidance. Operative technique: After preoperative computed tomography and bronchoscopy, a right thoracoscopic approach is utilized. The esophagus is mobilized and the membranous trachea is sutured to the prevertebral fascia under direct bronchoscopic visualization. Immediate improvement in tracheal collapse is noted. No major complications are reported and length of stay is short. Aortopexy may also be required to address anterior vascular compression. Conclusion: Thoracoscopic posterior tracheopexy is safe and feasible. Further studies with more patients and longer follow-up are needed to assess durability. (C) 2018 Elsevier Inc. All rights reserved.

The incidence of Crohn's disease in the pediatric population is increasing. While pediatric patients with Crohn's disease exhibit many of the characteristics of older patients, there are important differences in the clinical presentation and course of disease that can impact the clinical decisions made during treatment. The majority of children are diagnosed in the early teen years, but subgroups of very early onset and infantile Crohn's present much earlier and have a unique clinical course. Treatment paradigms follow the traditional laddered approach, but growth and development represent special considerations that must be given to pediatric-specific complications of the treatment and disease. Surgical intervention is an important component of Crohn's management and is often employed to allow improved nutritional intake or decrease reliance on medical treatments that compromise growth.

Adamantinoma is a rare, low-grade malignant tumor of the bone which grows slowly and typically occurs in the diaphysis of long bones, particularly in the tibia. Adamantinomas have the potential for local recurrence and may metastasize to the lungs, lymph nodes, or bone. We report a case of a 14-year-old female with a tibial adamantinoma who underwent wide resection with limb salvage and has subsequently been followed up for 18 years. The patient went on to have both a local soft tissue recurrence 5 years after the resection and metastases to both an inguinal lymph node and the right lower lobe of the lung 8 years after that recurrence, all of which have been treated successfully with marginal resections. Unique to this case, the patient was also incidentally found to have chromophobe-type renal cell carcinoma when undergoing a partial nephrectomy to resect a presumed metastasis of her adamantinoma. Genetic testing has not revealed any known genetic predisposition to cancer.

Purpose: Right sided aortic arch (RAA) is a rare anatomic finding in infants with esophageal atresia with or without tracheoesophageal fistula (EA/TEF). In the presence of RAA, significant controversy exists regarding optimal side for thoracotomy in repair of the EA/TEF. The purpose of this study was to characterize the incidence, demographics, surgical approach, and outcomes of patients with RAA and EA/TEF. Methods: A multi-institutional, IRB approved, retrospective cohort study of infants with EA/TEF treated at 11 children's hospitals in the United States over a 5-year period (2009 to 2014) was performed. All patients had a minimum of one-year follow-up. Results: In a cohort of 396 infants with esophageal atresia, 20 (5%) had RAA, with 18 having EA with a distal TEF and 2 with pure EA. Compared to infants with left sided arch (LAA), RAA infants had a lower median birth weight, (1.96 kg (IQR 1.54-2.65) vs. 2.57 kg (2.00-3.03), p = 0.01), earlier gestational age (34.5 weeks (IQR 32-37) vs. 37 weeks (35-39), p = 0.01), and a higher incidence of congenital heart disease (90% vs. 32%, p < 0.0001). The most common cardiac lesions in the RAA group were ventricular septal defect (7), tetralogy of Fallot (7) and vascular ring (5). Seventeen infants with RAA underwent successful EA repair, 12 (71%) via right thoracotomy and 5 (29%) through left thoracotomy. Anastomotic strictures trended toward a difference in RAA patients undergoing right thoracotomy for primary repair of their EA/TEF compared to left thoracotomy (50% vs. 0%, p=0.1). Side of thoracotomy in RAA patients undergoing EA/TEF repair was not significantly associated with mortality, anastomotic leak, recurrent laryngeal nerve injury, recurrent fistula, or esophageal dehiscence (all p > 0.29). Conclusion: RAA in infants with EA/TEF is rare with an incidence of 5%. Compared to infants with EA/TEF and LAA, infants with EA/TEF and RAA are more severely ill with lower birth weight and higher rates of prematurity and complex congenital heart disease. In neonates with RAA, surgical repair of the EA/TEF is technically feasible via thoracotomy from either chest. A higher incidence of anastomotic strictures may occur with a right-sided approach. (c) 2018 Elsevier Inc. All rights reserved.

Purpose: Appendiceal carcinoid tumors are rare neuroendocrine neoplasms. The aim of this study was to determine if postoperative oncologic follow-up was necessary for this tumor.Methods: A retrospective review was performed of patients with appendiceal carcinoid 2000-2015.Results: 8382 patients underwent appendectomy 2000-2015. 30 (0.3%) had appendiceal carcinoid. 70% were female (n = 21) with an average age of 13.5 +/- 2.8 years (range 8-18). Most presented with abdominal pain (n = 29, 97%). 20% (n = 6) had appendiceal perforation. Mean tumor size was 5.4 +/- 4mm (range microscopic - 15mm) with most at the appendiceal tip (n = 18, 60%). No node infiltration was found, although 10% (n = 3) had perineural and 3% (n = 1) had lymphovascular invasion. Five were transmural (17%). Most patients were referred to oncology (n = 19, 63%) for staging and surveillance including ultrasonography (n = 11, 65%), MRI (n = 7, 41%), and CT (n = 6, 35%). The majority (79%, n = 15) underwent serial 5-HIAA testing. All surveillance was found to be normal, and no patients required further treatment. Mean follow-up was 36 +/- 34 months, with 58% (n = 11) continuing surveillance. Medical charges ranged $8500-$44,000. No recurrences have been identified.Conclusion: Appendectomy is an adequate treatment for pediatric appendiceal carcinoid < 16 mm despite presence of histological risk factors. More aggressive surgery and extensive oncologic follow up are of limited value. Level of evidence: III.Type of study: Retrospective comparative study. (C) 2017 Elsevier Inc. All rights reserved.

Purpose of the ReviewEsophageal atresia remains a complex congenital anomaly that manifests in a number of different variants ranging from pure atresia to trachea-esophageal fistula without atresia. The surgical treatment options have continued to evolve with advances in technology and innovative procedures but the results for the patients with long-gap atresia remain challenging.Recent FindingsDocumenting the outcomes from interventions in this population is difficult given the limited experience at most centers and the heterogeneity of the anomalies and the treatments. Several recent studies have provided comparison data for some newer. Studies demonstrate better results in primary procedures than secondary operations but significant morbidity remains.Another innovation has been application of minimally invasive procedures to all forms of esophageal atresia. Reports of excellent results are encouraging with a theoretical reduction in the risk of long-term chest wall abnormalities.SummaryEsophageal atresia remains one of the most challenging congenital abnormalities requiring surgical intervention. While some progress has been made, dramatic impact awaits advances in tissue engineering or other game changing developments.