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.

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.

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.

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.

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.

Prognostic factors and survival in pediatric and adolescent liposarcoma.

Purpose. Liposarcoma is extremely rare in the pediatric population. To identify prognostic factors and determine treatment outcomes, we reviewed our institutional experience with pediatric liposarcoma. Methods. We retrospectively reviewed all pediatric patients (age <22 years) with confirmed liposarcoma treated at Memorial Sloan-Kettering Cancer Center. Histologic subtype, tumor location, margin status, recurrence, and adjuvant therapy were analyzed and correlated with overall survival. Results. Thirty-four patients (56% male) with a median age of 18.1 years were identified. Twenty-two (65%) had peripheral tumors and 12 (35%) had centrally located tumors. Histologically, 29 (85%) tumors were low grade, and 5 (15%) were high grade pleomorphic. Eleven (32%) had recurrent disease, 9 patients with central tumors and 2 patients with peripheral lesions. Eight deaths occurred, all in patients with central disease. Five-year overall survival was 78%, with a median follow-up time of 5.4 years (range, 0.3-30.3 years). Tumor grade (P = .003), histologic subtype (P = .01), and primary location (P < .001) all correlated with survival, as did stage (P < .001) and margin status (P = .001). Conclusions. Central location of the primary tumor, high tumor grade, and positive surgical margins are strongly correlated with poor survival in pediatric patients with liposarcoma.

Variability in opioid pain medication prescribing for adolescent trauma patients in a sample of US pediatric trauma centers.

Objectives: The primary objective of this study was to examine opioid prescription frequency and identify differences across a national cohort of pediatric trauma centers in rates of prescribing opioids to injured adolescents at discharge. Methods: This was a retrospective observational study using electronic health records of injured adolescents (12-17 years) admitted to one of 10 pediatric trauma centers. Results: Of the 1345 electronic health records abstracted, 720 (53.5%, 95% CI 50.8 to 56.2) patients received opioid prescriptions at discharge with variability across sites (28.6%-72%). There was no association between patient factors and frequency of prescribing opioids. Center's trauma volume was significantly positively correlated with a higher rate of opioid prescribing at discharge (r=0.92, p=0.001). There was no significant difference between the frequency of opioid prescriptions at discharge among alcohol and other drugs (AOD)-positive patients (53.8%) compared with AOD-negative patients (53.5%). Conclusions: Across a sample of 10 pediatric trauma centers, just over half of adolescent trauma patients received an opioid prescription at discharge. Prescribing rates were similar for adolescent patients screening positive for AOD use and those screening negative. The only factor associated with a higher frequency of prescribing was trauma center volume. Consensus and dissemination of outpatient pain management best practices for adolescent trauma patients is warranted. Level of evidence: III-prognostic. Trial registration number: NCT03297060.

Outcomes following adoption of a standardized protocol for abscess drain management in pediatric appendicitis.

BACKGROUND/PURPOSE: Though evidence-based clinical pathways for the diagnosis and treatment of pediatric appendicitis have been established, protocols guiding management of percutaneous abscess drains are lacking. We hypothesized a drain management protocol utilizing drain output and clinical factors instead of fluoroscopic drain studies would reduce interventional radiologic procedures without adversely impacting clinical outcomes. METHODS: A standardized protocol was uniformly adopted at a tertiary-care children's hospital in April 2016. A retrospective chart review included all cases of appendicitis requiring abscess drainage by interventional radiology three years pre- and postprotocol implementation. RESULTS: Fifty-eight patients (preprotocol = 39, postprotocol = 19) underwent percutaneous abscess drainage, of whom 52 (preprotocol = 34, postprotocol = 18) required a drain. Baseline demographics and clinical presentation were similar across groups. Following protocol implementation, total number of IR procedures decreased from 2.4 to 1.3 per patient (p = 0.004). There was no significant difference in the number of postprocedure diagnostic imaging studies, readmissions, or inpatient days, and there was a trend towards a decrease in number of drain days (10.7 to 5.7, p = 0.067). CONCLUSION: A standardized protocol for management of abscess drains for complicated appendicitis reduced the number of IR procedures without a negative impact on clinical outcomes or increase in alternative imaging studies. This approach may decrease radiation exposure, anesthetic administration, and resource utilization. TYPE OF STUDY: Treatment study (retrospective comparative study). LEVEL OF EVIDENCE: Level III.

Late-onset kidney failure in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

BACKGROUND: The incidence of and risk factors for late-onset kidney failure among survivors over the very long term remains understudied. MATERIALS AND METHODS: A total of 25,530 childhood cancer survivors (median follow-up 22.3 years, interquartile range 17.4-28.8) diagnosed between 1970 and 1999, and 5045 siblings from the Childhood Cancer Survivor Study were assessed for self-reported late-onset kidney failure, defined as dialysis, renal transplantation, or death attributable to kidney disease. Piecewise exponential models evaluated associations between risk factors and the rate of late-onset kidney failure. RESULTS: A total of 206 survivors and 10 siblings developed late-onset kidney failure, a 35-year cumulative incidence of 1.7% (95% confidence interval [CI] = 1.4-1.9) and 0.2% (95% confidence interval [CI] = 0.1-0.4), respectively, corresponding to an adjusted rate ratio (RR) of 4.9 (95% CI = 2.6-9.2). High kidney dose from radiotherapy (≥15Gy; RR = 4.0, 95% CI = 2.1-7.4), exposure to high-dose anthracycline (≥250 mg/m2; RR = 1.6, 95% CI = 1.0-2.6) or any ifosfamide chemotherapy (RR = 2.6, 95% CI = 1.2-5.7), and nephrectomy (RR = 1.9, 95% CI = 1.0-3.4) were independently associated with elevated risk for late-onset kidney failure among survivors. Survivors who developed hypertension, particularly in the context of prior nephrectomy (RR = 14.4, 95% CI = 7.1-29.4 hypertension with prior nephrectomy; RR = 5.9, 95% CI = 3.3-10.5 hypertension without prior nephrectomy), or diabetes (RR = 2.2, 95%CI = 1.2-4.2) were also at elevated risk for late-onset kidney failure. CONCLUSIONS: Survivors of childhood cancer are at increased risk for late-onset kidney failure. Kidney dose from radiotherapy ≥15 Gy, high-dose anthracycline, any ifosfamide, and nephrectomy were associated with increased risk of late-onset kidney failure among survivors. Successful diagnosis and management of modifiable risk factors such as diabetes and hypertension may mitigate the risk for late-onset kidney failure. The association of late-onset kidney failure with anthracycline chemotherapy represents a novel finding that warrants further study.

Effects of metalloproteinase inhibition in a murine model of renal ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) is a leading cause of acute tubular necrosis (ATN) and delayed graft function in transplanted organs. Up-regulation of matrix metalloproteinases (MMPs) propagates the microinflammatory response that drives IRI. This study sought to determine the specific effects of Marimastat (Vernalis, BB-2516), a broad spectrum MMP and TNF-alpha-converting enzyme inhibitor, on IRI-induced ATN. Mice were pretreated with Marimastat or methylcellulose vehicle for 4 d before surgery. Renal pedicles were bilaterally occluded for 30 min and allowed to reperfuse for 24 h. Baseline creatinine levels were consistent between experimental groups; however, post-IRI creatinine levels were 4-fold higher in control mice (p < 0.0001). The mean difference between the post-IRI histology grades of Marimastat-treated and control kidneys was 1.57 (p = 0.003), demonstrating more severe damage to control kidneys. Post-IRI mean (+/-SEM) MMP-2 activity rose from baseline levels in control mice (3.62 +/- 0.99); however, pretreated mice presented only a slight increase in mean MMP-2 activity (1.57 +/- 0.72) (p < 0.001). In conclusion, these data demonstrate that MMP inhibition is associated with a reduction of IRI in a murine model.

Pediatric differentiated thyroid carcinoma: An update from the APSA Cancer Committee.

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).

What's new in pediatric melanoma: An update from the APSA cancer committee.

BACKGROUND/PURPOSE: Melanoma is the most common skin cancer in children and often presents in an atypical fashion when compared to adults. The purpose of this review is to present an update on the epidemiology, surgical and medical management and prevention strategies in pediatric melanoma. METHODS: A comprehensive review of the current literature on the epidemiology, surgical and medical management and prevention of adult and pediatric melanoma was performed by the authors and the results of this review are summarized in the manuscript. RESULTS: Most recently, the incidence of melanoma in children has been declining, possibly owing to increased awareness and sun exposure prevention. The mainstay of therapy is surgical resection, often with sentinel lymph node biopsy. A positive sentinel node has prognostic value; however, completion node dissection is no longer recommended in the absence of clinically or radiographically positive nodes. Those with advanced disease also receive adjuvant systemic therapy using increasingly targeted immunologic therapies. CONCLUSIONS: Sentinel lymph node positive patients no longer require completion lymph node dissection and instead may be followed by ultrasound. However, it is important to note that children have been excluded from most melanoma clinical trials to date, and therefore, recommendations for management are based on existing pediatric retrospective data and extrapolation from adult studies. LEVEL OF EVIDENCE: IV.