Children's Oncology Group's 2023 blueprint for research: Surgery.

Surgery plays a crucial role in the treatment of children with solid malignancies. A well-conducted operation is often essential for cure. Collaboration with the primary care team is important for determining if and when surgery should be performed, and if performed, an operation must be done in accordance with well-established standards. The long-term consequences of surgery also need to be considered. Indications and objectives for a procedure vary. Providing education and developing and analyzing new research protocols that include aims relevant to surgery are key objectives of the Surgery Discipline of the Children's Oncology Group. The critical evaluation of emerging technologies to ensure safe, effective procedures is another key objective. Through research, education, and advancing technologies, the role of the pediatric surgeon in the multidisciplinary care of children with solid malignancies will continue to evolve.

Children's Oncology Group's 2023 blueprint for research: Rare tumors.

The Children's Oncology Group (COG) Rare Tumor Committee includes the Infrequent Tumor and Retinoblastoma subcommittees, encompassing a wide range of extracranial solid tumors that do not fall within another COG disease committee. Current therapeutic trial development focuses on nasopharyngeal carcinoma, adrenocortical carcinoma, pleuropulmonary blastoma, colorectal carcinoma, melanoma, and thyroid carcinoma. Given the rarity of these tumors, novel strategies and international collaborative efforts are necessary to advance research and improve outcomes.

Pulmonary Metastasis of Low-risk Perinatal Neuroblastoma After Resection: Implications for Surveillance.

In the wake of the Children's Oncology Group (COG) ANBL00P2 trial and the ongoing ANBL1232 trial, an increasing number of children with neonatal neuroblastoma are being managed nonoperatively. We report the case of a patient with low-risk, non-MYCN amplified, neuroblastoma that was diagnosed and resected in the neonatal period but subsequently developed pulmonary metastases by the age of 7 months. Though rare, the possibility of low-risk disease metastasizing during surveillance should be recognized and may not be identified by current protocols.

APC mutational patterns in gastric adenocarcinoma are enriched for missense variants with associated decreased survival.

Adenomatous polyposis coli (APC) mutations are causally associated with familial adenomatous polyposis (FAP) and are recurrent somatic events across numerous tumor types, including gastric adenocarcinoma. Severity of disease in FAP correlates with specific APC mutations, but the impact of given mutations on phenotype in gastric cancer is not well studied. Sequencing data from the Genomic Data Commons (GDC) demonstrate an APC mutational pattern in gastric cancer that differs dramatically from that seen in colon cancer. Exome sequencing data from APC-mutant colon and gastric adenocarcinomas in GDC was filtered for single nucleotide variants (SNVs) using MuTect2 Variant Aggregation and Masking pipeline, Somatic Aggregation Workflow. APC mutations were found in 57/441 gastric (12.9%) and 309/433 colon adenocarcinomas (71.4%). There was a significant difference in the proportion of stopgain, frameshift, and missense mutations between tumor types(P < .00001). Colon tumors were predominated by frameshift and stopgains, comprising 47.7% and 35.7%, respectively. In contrast, 47.1% of gastric mutations were missense. Gastric tumors harboring missense mutations showed decreased overall survival relative to other mutational subtypes(P = .008). In the gastric samples, 25.9% of frameshift and stopgain mutations are in the 3' portion of the gene, compared to 1.4% of colon samples. APC mutations demonstrate different distributions in gastric and colon adenocarcinoma, with a shift toward missense variants in gastric tumors and worse survival in gastric tumors harboring them. As different mutations confer variable degrees of protein dysfunction and resultant clinical manifestation, expanded investigation of specific mutational patterns will prove integral to future-risk stratification strategies.

Recurrence and Complications in Pediatric and Adolescent Papillary Thyroid Cancer in a High-Volume Practice.

BACKGROUND: Treatment approaches for pediatric papillary thyroid cancer (PTC) are historically extrapolated from adult experience. However, pediatric PTC demonstrates a greater propensity for lymph node involvement, early metastases, and recurrence, highlighting the need for pediatric-specific treatment paradigms. MATERIALS AND METHODS: A retrospective review included patients with PTC aged ≤21 y, with ≥18 mo of follow-up, treated between 2002 and 2015. Fisher's exact test and Cox proportional hazard were used to estimate the effect of risk factors on disease recurrence. RESULTS: Seventy-two cases of PTC were identified with median age of 17.0 y and median follow-up of 64.1 mo. Disease recurred at a median of 24.6 mo (range 7.8-78.1) in 7 of 51 (13.7%) of patients with disease limited to the thyroid or central neck, 7 of 18 (39%) patients with lateral neck disease at presentation who underwent a compartment-based resection, and three of three patients (100%) with lateral neck disease who sought care after non-compartment-based resection. There were no deaths from disease. Univariate predictors of recurrence included tumor size >2 cm (P = 0.005), lateral neck disease (P = 0.004), lymphovascular invasion (P = 0.017), extracapsular invasion (P < 0.0001), multifocality (P = 0.03), and non-Caucasian race (P = 0.05). Multivariate analysis identified race (P = 0.05) as an independent predictor of recurrence. In patients without lateral neck disease, there was a trend toward lower recurrence in patients undergoing thyroidectomy with central neck dissection compared with thyroidectomy alone (P = 0.07). CONCLUSIONS: Pediatric PTC is associated with excellent survival, although recurrence is common in patients with lateral node involvement. Predictors of recurrence are multifactorial and may be influenced by extent of disease, patient or tumor biology, and aggressiveness of resection. LEVEL OF EVIDENCE: Prognosis study, level IV, retrospective case series.

Opioid Prescribing Habits of General Versus Pediatric Surgeons After Uncomplicated Laparoscopic Appendectomy.

BACKGROUND: Adolescents who use prescription opioids have an increased risk for future drug abuse and overdose, making them a high-risk population. Appendectomy is one of the most common surgical procedures in this age group, often requires opioid analgesia, and is performed by both pediatric and general surgeons. Prescription patterns comparing these two provider groups have not yet been evaluated; we hypothesize that general surgery providers prescribe more opioids for adolescent and young adult patients than do pediatric surgery providers. METHODS: A retrospective chart review was conducted across a single health system consisting of four hospitals. All uncomplicated laparoscopic appendectomies performed between January 1, 2016 and August 14, 2017 on patients aged 7-20 were included for analysis. Any case coded for multiple procedures, identified as converted to open, or had a length of stay >48 h were excluded. The primary outcome measure was amount of opioid prescribed postoperatively. To standardize different formulations and types of analgesia prescribed, prescriptions were converted into oral morphine equivalents (OMEs). For reference, one 5 mg pill of oxycodone equals 7.5 OME. Linear regression was performed controlling for patient weight, gender, race, insurance status, provider type (pediatric versus general surgery), and provider level (resident, advanced practice provider, and attending). RESULTS: A total of 336 pediatric laparoscopic appendectomies were analyzed, 148 by general surgeons and 188 by pediatric surgeons. Pediatric surgeons prescribed less opioid than general surgeons overall (59 OME versus 90 OME, P < 0.0001). For patients aged <13 y, there was no significant difference between pediatric (26 OME) and general (37 OME, P = 0.8921) surgeons. However, for the age group 13-20 y, pediatric surgeons prescribed 25% less opioid than general surgeons (90 OME versus 112.5 OME, P < 0.0001). Regression analysis demonstrated that being cared for by a general surgery service (+24.1 OME [95% confidence interval 9.8-38.3]) was associated with high prescribing, whereas having Medicaid was associated with lower prescription amounts (-16.4 OME [95% confidence interval -32.5 to -0.3]). CONCLUSIONS: After an uncomplicated laparoscopic appendectomy, general surgeons prescribe significantly more opioid to adolescent patients than do pediatric surgeons, even when controlling for age and weight. One substantial and modifiable contributor of the opioid epidemic is the amount of opioid prescribed. The variability of prescribing habits to adolescents and young adults demonstrates a clear need for increased education and guidelines on this topic, especially for surgeons who do not frequently treat the younger and more vulnerable population.

Early Involvement of the Child Protection Team in the Care of Injured Infants in a Pediatric Emergency Department.

BACKGROUND: Physical abuse is a significant cause of infant morbidity and mortality. Early detection in the emergency department (ED) is crucial. OBJECTIVE: We describe the impact of a clinical pathway focused on early involvement of the child protection team (CPT) and social work (SW) team for infants presenting to a pediatric emergency department with an injury concerning for abuse. METHODS: The pathway lists 10 injuries associated with abuse in infants and directs consultation of the CPT and SW. It was implemented at a single site on April 1, 2014. Seasonally matched data were collected 12 months before and after implementation on all children < 12 months of age with a qualifying injury. Demographics, CPT and SW consults, referral to Child Protective Services, diagnostic studies, and ultimate determination of abuse by the CPT were collected. RESULTS: Implementation of the pathway was associated with an increase in consultation of the CPT from 17% to 47% (p < 0.001) and SW from 33% to 52% (p < 0.001). CPT and SW consultations were obtained more frequently for those on public compared to private insurance prior to implementation but not after (CPT: odds ratio [OR] 4.32; p = 0.046; 95% confidence interval [CI] 1.03-18.15; SW: OR 3.23, p = 0.034; 95% CI 1.09-9.74). Diagnostic testing increased in the post-pathway period. There was no difference in the detection of abusive injury or number of missed cases. CONCLUSIONS: These findings suggest that this clinical pathway was successful in increasing involvement of the CPT and SW teams and reducing socioeconomic disparity in the evaluation of infants with injuries concerning for abuse.

A Qualitative Study of Multidisciplinary Providers' Experiences With the Transfer Process for Injured Children and Ideas for Improvement.

OBJECTIVE: Most injured children initially present to a community hospital, and many will require transfer to a regional pediatric trauma center. The purpose of this study was 1) to explore multidisciplinary providers' experiences with the process of transferring injured children and 2) to describe proposed ideas for process improvement. METHODS: This qualitative study involved 26 semistructured interviews. Subjects were recruited from 6 community hospital emergency departments and the trauma and transport teams of a level I pediatric trauma center in New Haven, Conn. Participants (n = 34) included interprofessional providers from sending facilities, transport teams, and receiving facilities. Using the constant comparative method, a multidisciplinary team coded transcripts and collectively refined codes to generate recurrent themes across interviews until theoretical saturation was achieved. RESULTS: Participants reported that the transfer process for injured children is complex, stressful, and necessitates collaboration. The transfer process was perceived to involve numerous interrelated components, including professions, disciplines, and institutions. The 5 themes identified as areas to improve this transfer process included 1) Creation of a unified standard operating procedure that crosses institutions/teams, 2) Enhancing 'shared sense making' of all providers, 3) Improving provider confidence, expertise, and skills in caring for pediatric trauma transfer cases, 4) Addressing organization and environmental factors that may impede/delay transfer, and 5) Fostering institutional and personal relationships. CONCLUSIONS: Efforts to improve the transfer process for injured children should be guided by the experiences of and input from multidisciplinary frontline emergency providers.

Surgical tray optimization as a simple means to decrease perioperative costs.

BACKGROUND: Health care spending in the US remains excessively high. Aside from complicated, large-scale efforts at health care cost reduction, there are still relatively simple ways in which individual hospitals can cut unnecessary costs from everyday operations. Inspired by recent publications, our group sought to decrease the costs associated with surgical instrument processing at a large, multihospital academic center. METHODS: This was a single-site observational study conducted at a large academic medical center. At the study start, all attending surgeons within the section of pediatric surgery agreed to standardize the pediatric surgery trays and to eliminate instruments that were deemed unnecessary from each tray. A multidisciplinary start-up meeting was held, and this meeting included stakeholders from central sterile processing, operating room nursing, scrub technicians, and materials management along with all five pediatric surgeons. Each tray was addressed individually. Instruments were eliminated from trays only if there was unanimous agreement among all the surgeons in the group. If no instruments in a given surgical tray were deemed necessary, the entire tray was eliminated from sterile processing rotation. Feedback questionnaires were drafted by the multidisciplinary team that participated in the start-up meeting. Surgeons were allowed to request for certain instruments to be placed back into the trays at any time, and the questionnaires also allowed for free-hand comments. Surgical kit preparation time was obtained from the institutional barcode scanning system. The cost per second of sterile processing labor was calculated using regional median salary for sterile processing technicians in the state of Connecticut. Using the pediatric surgery section as the model unit, this method was then applied to pediatric urology, neurosurgery, spine surgery, and orthopedics. RESULTS: The pediatric surgery section eliminated an average of 59.5% of instruments per tray, resulting in an overall reduction of 1826 (39.5%) instruments from rotation, 45,856 fewer instruments processed per year, and nine trays eliminated completely from regular rotation. Processing time for six commonly used trays was reduced by an average of 28.7%. The urology section eliminated 18 trays from regular rotation and 179 (10.1%) instruments in total. Pediatric orthopedics, neurosurgery, and spine sections eliminated 708 (17.1%), 560 (92.7%), and 31 (32.2%) instruments, respectively, resulting in approximately 18,804 fewer instruments processed per year. Among all five surgical sections, annual instrument cost avoidance after tray optimization was estimated at $53,193 to $531,929 using average instrument life spans ranging from 1-10 y. Negative feedback and requests for instrument replacement were both minimal on feedback questionnaires. CONCLUSIONS: Surgical tray optimization represents a relatively simple microsystem improvement that could result in significant hospital cost reduction. Although difficult to quantify, other gains from surgical kit optimization include decreased weight per tray, decreased materials cost, and decreased labor required to count, decontaminate, and pack surgical trays.

NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States.

BACKGROUND: An increase in thyroid cancers, predominantly papillary thyroid carcinoma (PTC), has been recently reported in children. METHODS: The histopathology of 28 consecutive PTCs from the northeast United States was reviewed. None of the patients (ages 6-18 years; 20 females, 8 males) had significant exposure to radiation. Nucleic acid from tumors was tested for genetic abnormalities (n = 27). Negative results were reevaluated by targeted next-generation sequencing. RESULTS: Seven of 27 PTCs (26%) had neurotrophic tyrosine kinase receptor (NTRK) fusion oncogenes (NTRK type 3/ets variant 6 [NTRK3/ETV6], n =5; NTRK3/unknown, n = 1; and NTRK type 1/translocated promoter region, nuclear basket protein [NTRK1/TPR], n = 1), including 5 tumors that measured >2 cm and 3 that diffusely involved the entire thyroid or lobe. All 7 tumors had lymphatic invasion, and 5 had vascular invasion. Six of 27 PTCs (22%) had ret proto-oncogene (RET) fusions (RET/PTC1, n = 5; RET/PTC3, n = 1); 2 tumors measured >2 cm and diffusely involved the thyroid, and 5 had lymphatic invasion, with vascular invasion in 2. Thirteen PTCs had the B-Raf proto-oncogene, serine/threonine kinase (BRAF) valine-to-glutamic acid mutation at position 600 (BRAF(V) (600E)) (13 of 27 tumors; 48%), 11 measured <2 cm, and 6 had lymphatic invasion (46%), with vascular invasion in 3. Fusion oncogene tumors, compared with BRAF(V) (600E) PTCs, were associated with large size (mean, 2.2 cm vs 1.5 cm, respectively; P = .05), solid and diffuse variants (11 of 13 vs 0 of 13 tumors, respectively; P < .001), and lymphovascular invasion (12 of 13 vs 6 of 13 tumors, respectively; P = .02); BRAF(V) (600E) PTCs were predominantly the classic variant (12 of 13 vs 1 of 13 tumors). Two tumors metastasized to the lung, and both had fusion oncogenes (NTRK1/TPR, n = 1; RET/PTC1, n = 1). CONCLUSIONS: Fusion oncogene PTC presents with more extensive disease and aggressive pathology than BRAF(V) (600E) PTC in the pediatric population. The high prevalence of the NTRK1/NTRK3 fusion oncogene PTCs in the United States is unusual and needs further investigation.

Shifting patterns of genomic variation in the somatic evolution of papillary thyroid carcinoma.

BACKGROUND: Cancer is increasingly understood to arise in the context of dynamically evolving genomes with continuously generated variants subject to selective pressures. Diverse mutations have been identified in papillary thyroid carcinoma (PTC), but unifying theories underlying genomic change are lacking. Applying a framework of somatic evolution, we sought to broaden understanding of the PTC genome through identification of global trends that help explain risk of tumorigenesis. METHODS: Exome sequencing was performed on 53 PTC and matched adjacent non-tumor thyroid tissues (ANT). Single nucleotide substitution (SNS) signatures from each sample pair were divided into three subsets based on their presence in tumor, non-tumor thyroid, or both. Nine matched blood samples were sequenced and SNS signatures intersected with these three subsets. The intersected genomic signatures were used to define branch-points in the evolution of the tumor genome, distinguishing variants present in the tissues' common ancestor cells from those unique to each tissue type and therefore acquired after genomic divergence of the tumor, non-tumor, and blood samples. RESULTS: Single nucleotide substitutions shared by the tumor and the non-tumor thyroid were dominated by C-to-T transitions, whereas those unique to either tissue type were enriched for C-to-A transversions encoding non-synonymous, predicted-deleterious variants. On average, SNSs of matched blood samples were 81 % identical to those shared by tumor and non-tumor thyroid, but only 12.5 % identical to those unique to either tissue. Older age and BRAF mutation were associated with increased SNS burden. CONCLUSIONS: The current study demonstrates novel patterns of genomic change in PTC, supporting a theory of somatic evolution in which the zygote's germline genome undergoes continuous remodeling to produce progressively differentiated, tissue-specific signatures. Late somatic events in thyroid tissue demonstrate shifted mutational spectra compared to earlier polymorphisms. These late events are enriched for predicted-deleterious variants, suggesting a mechanism of genomic instability in PTC tumorigenesis.

Pediatric thymomas: report of two cases and comprehensive review of the literature.

PURPOSE: Thymomas are rare pediatric malignancies with indolent behavior. There are fewer than 50 reported cases and no comprehensive review. We sought to evaluate our recent experience with pediatric thymomas, and comprehensively review the extant literature. METHODS: A systematic search of the PubMed database was performed using keywords: "thymoma", "pediatric", "juvenile", "childhood", and "child". Additional studies were identified by a manual search of the reference list. RESULTS: We report two patients with thymomas. We identified 22 case reports or series that described 48 patients; 62 % were male, 15 % presented with myasthenia gravis. Fifty percent were Masaoka Stage I, 15 % were Stage II, 13 % were Stage III, and 23 % were Stage IV. Four patients with early stage (I or II) disease were treated with adjuvant therapies in addition to surgical excision, while five patients with late stage (III or IV) disease treated with surgical excision alone. Of studies reporting at least 2-year follow-up, survival was 71 %. CONCLUSION: Pediatric thymomas are rare tumors with a slight male predominance. Wide variations were observed in the treatment of thymomas across all stages. Our review indicates a need for large database and multi-institutional studies to clearly elucidate clinical course, prognostic factors and outcome.

Molecular Genetics Augment Cytopathologic Evaluation and Surgical Planning of Pediatric Thyroid Nodules.

PURPOSE: Molecular genetic testing in conjunction with cytopathology may improve prediction of malignancy in thyroid nodules, particularly those with indeterminate cytology (Bethesda III/IV). Though now commonplace in adults, pediatric data are limited. This study examines molecular genetics of pediatric nodules with correlation to cytologic and histologic classification at time of surgery and the distribution of mutations. METHODS: Retrospective chart review of 164 patients <22 years who underwent surgical resection of a thyroid nodule between 2002 and 2020 with molecular testing on fine-needle aspiration biopsy (FNA) or final histopathology. RESULTS: 85 (52 %) of 164 patients undergoing thyroid resection had available molecular genetic testing. BRAF V600E testing was performed on the FNA samples of 73 (86 %) patients and on 15 (18 %) surgical specimens; 31 (37 %) were positive. Of the remaining 54 patients, 21 had additional mutation/fusion testing. In 17 (81 %) cases, an alternate mutation/fusion was identified including 8 gene fusions, 3 DICER1 mutations, 4 NRAS mutations, one BRAF variant, and one unknown variant. BRAF, DICER1 mutations, and gene fusions predicted malignancy. Greater than 95 % of BRAF mutations were in Bethesda V/VI lesions and associated with classic variant PTC whereas fusions and DICER1 mutations clustered in Bethesda IV nodules. Bethesda III nodules harbored BRAF and NRAS mutations. In Bethesda IV nodules, a gene fusion or DICER mutation altered the surgical decision-making (upfront thyroidectomy rather than lobectomy) in 70 % of nodules submitted for genetic testing. CONCLUSION: Expanded molecular genetic testing on FNA of pediatric thyroid nodules, particularly Bethesda III/IV, may improve prediction of malignancy and augment surgical decision-making. LEVEL OF EVIDENCE: III.

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.

Management and Outcomes of Pediatric Lymphatic Malformations: A Systematic Review From the APSA Outcomes and Evidence-Based Practice Committee.

BACKGROUND: Significant variation in management strategies for lymphatic malformations (LMs) in children persists. The goal of this systematic review is to summarize outcomes for medical therapy, sclerotherapy, and surgery, and to provide evidence-based recommendations regarding the treatment. METHODS: Three questions regarding LM management were generated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Publicly available databases were queried to identify articles published from January 1, 1990, to December 31, 2021. A consensus statement of recommendations was generated in response to each question. RESULTS: The initial search identified 9326 abstracts, each reviewed by two authors. A total of 600 abstracts met selection criteria for full manuscript review with 202 subsequently utilized for extraction of data. Medical therapy, such as sirolimus, can be used as an adjunct with percutaneous treatments or surgery, or for extensive LM. Sclerotherapy can achieve partial or complete response in over 90% of patients and is most effective for macrocystic lesions. Depending on the size, extent, and location of the malformation, surgery can be considered. CONCLUSION: Evidence supporting best practices for the safety and effectiveness of management for LMs is currently of moderate quality. Many patients benefit from multi-modal treatment determined by the extent and type of LM. A multidisciplinary approach is recommended to determine the optimal individualized treatment for each patient.

Screening and Prophylaxis for Venous Thromboembolism in Pediatric Surgery: A Systematic Review.

OBJECTIVE: The American Pediatric Surgical Association Outcomes and Evidence-Based Practice Committee conducted a systematic review to describe the epidemiology of venous thromboembolism (VTE) in pediatric surgical and trauma patients and develop recommendations for screening and prophylaxis. METHODS: The Medline (Ovid), Embase, Cochrane, and Web of Science databases were queried from January 2000 through December 2021. Search terms addressed the following topics: incidence, ultrasound screening, and mechanical and pharmacologic prophylaxis. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. Consensus recommendations were derived based on the best available literature. RESULTS: One hundred twenty-four studies were included. The incidence of VTE in pediatric surgical populations is 0.29% (Range = 0.1%-0.48%) and directly correlates with surgery type, transfusion, prolonged anesthesia, malignancy, congenital heart disease, inflammatory bowel disease, infection, and female sex. The incidence of VTE in pediatric trauma populations is 0.25% (Range = 0.1%-0.8%) and directly correlates with injury severity, major surgery, central line placement, body mass index, spinal cord injury, and length-of-stay. Routine ultrasound screening for VTE is not recommended. Consider sequential compression devices in at-risk nonmobile, pediatric surgical patients when an appropriate sized device is available. Consider mechanical prophylaxis alone or with pharmacologic prophylaxis in adolescents >15 y and post-pubertal children <15 y with injury severity scores >25. When utilizing pharmacologic prophylaxis, low molecular weight heparin is superior to unfractionated heparin. CONCLUSIONS: While VTE remains an infrequent complication in children, consideration of mechanical and pharmacologic prophylaxis is appropriate in certain populations. TYPE OF STUDY: Systematic Review of level 2-4 studies. LEVEL OF EVIDENCE: Level 3-4.

Pediatric and adolescent synovial sarcoma: multivariate analysis of prognostic factors and survival outcomes.

PURPOSE: Treatment of synovial sarcoma (SS) is challenging because of its unpredictable clinical behavior. We reviewed our institutional experience with pediatric SS to identify prognostic indicators and survival outcomes. METHODS: We retrospectively reviewed all pediatric/adolescent patients (age<22 years) with confirmed SS treated from 1970 to 2010. Patient and clinical characteristics were evaluated for prognostic significance and survival outcomes. RESULTS: We identified 111 patients. The median age was 15.4 years. Sixty-seven tumors (60%) were monophasic, 42 (38%) were biphasic, and 2 (2%) were of unknown histology. Median follow-up was 5.3 years (range 0.8-36.8 years), 5-year overall survival (OS) was 73%, and 10-year OS was 65%. Greater tumor size (stratified as ≤5 cm, >5 cm, or ≥10 cm) (P=0.001) and depth (P=0.03) correlated with decreased OS. Primary tumor location in the upper extremity correlated with increased OS when compared with lower-extremity and central lesions (P=0.05). Bone and/or neurovascular invasion negatively impacted survival (P=0.02). Multivariate analysis revealed that tumor size (trichotomized) was the dominant and sole factor in discriminating survival risk. Neither radiotherapy nor chemotherapy correlated with improved 5-year survival. CONCLUSIONS: Tumor size, depth, invasion, and primary location affect survival in pediatric SS. The role of radiotherapy and chemotherapy for SS warrants future study.

Efficacy and safety of thoracoscopic thymectomy in the treatment of juvenile myasthenia gravis.

BACKGROUND: Thymectomy is a well-established treatment for generalized myasthenia gravis in adults, but predictors of long-term efficacy and the optimum timing for intervention in juvenile myasthenia remain controversial. PURPOSE: To review the preoperative presentation, surgical experience, and long-term neuromuscular follow-up in patients undergoing thoracoscopic thymectomy in a single institution. METHODS: A retrospective chart review of all patients undergoing thoracoscopic thymectomy for myasthenia gravis at a tertiary referral center between 2000 and 2010 and compared to an historical cohort of trans-sternal thymectomies performed between 1970 and 1995. Age at diagnosis, presurgical medications and hospitalizations, preoperative chest imaging, presence of acetylcholinesterase antibodies, Osserman Stage, time to operative intervention, length of follow-up, DeFillipi remission scale, as well as operative and post-operative data (length of surgery, blood loss, need for chest tube, length of intubation, length of hospital stay, pathology, and complications) were recorded. RESULTS: Fifteen patients undergoing thoracoscopic thymectomy were identified with a mean age of 11.3 years at time of diagnosis and average treatment duration of 12.5 months prior to operative intervention. Of these patients, most presented with Osserman Stage IIB (8) or III (5) disease. Two patients presented with Osserman Stage IIa disease. There were no reported complications, no conversions to an open approach, and an average length of stay of 2.6 days. Average length of follow-up was 37.5 months, available on 13 of 15 patients. Nine of 13 (69 %) were improved (DeFillippi Class 2 or 3) at 1-month follow-up, however, the pattern of remission waxed and waned, with only 50 % reporting improvement at 1 year, 86 % at 2 years and 75 % at 3 years. Only one patient was totally off medication. No patients required postoperative hospitalization for respiratory crisis. CONCLUSIONS: Thoracoscopic thymectomy offers a safe approach to thymic resection in children with JMG with little associated morbidity and a short hospital stay, but should not be considered curative. Rather it appears to make generalized JMG more amenable to long-term medical management.

Vulvovaginal Complaints as the First Manifestation of Crohn's Disease in Children: Case Report.

BACKGROUND: Crohn's disease, a chronic gastrointestinal inflammatory condition, can involve gynecological structures. Rectovaginal or rectovestibular involvement may be the first sign in the pediatric population and may result in delayed diagnosis and treatment. CASE: A 9-year-old premenarchal female with chronic constipation and poor growth presented to the pediatric gynecologist for evaluation of persistent vulvovaginal discharge and vulvar irritation. Examination under anesthesia revealed a rectolabial fistula; colonoscopy was diagnostic of Crohn's disease. Immunotherapy resulted in improvement of symptoms and anatomical changes. SUMMARY AND CONCLUSION: In cases of persistent vulvar complaints in a child without clear diagnosis, a high index of suspicion for a non-gynecologic diagnosis is necessary. Collaboration between pediatric gynecologists, gastroenterologists, and surgeons can result in prompt diagnosis and treatment of genital Crohn's disease.

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.