Evaluation and Surgical Management of Pediatric Cutaneous Melanoma and Atypical Spitz and Non-Spitz Melanocytic Tumors (Melanocytomas): A Report From Children's Oncology Group.

PURPOSE: The purpose of this study was to develop recommendations for the diagnostic evaluation and surgical management of cutaneous melanoma (CM) and atypical Spitz tumors (AST) and non-Spitz melanocytic tumors (melanocytomas) in pediatric (age 0-10 years) and adolescent (age 11-18 years) patients. METHODS: A Children's Oncology Group-led panel with external, multidisciplinary CM specialists convened to develop recommendations on the basis of available data and expertise. RESULTS: Thirty-three experts from multiple specialties (cutaneous/medical/surgical oncology, dermatology, and dermatopathology) established recommendations with supporting data from 87 peer-reviewed publications. RECOMMENDATIONS: (1) Excisional biopsies with 1-3 mm margins should be performed when feasible for clinically suspicious melanocytic neoplasms. (2) Definitive surgical treatment for CM, including wide local excision and sentinel lymph node biopsy (SLNB), should follow National Comprehensive Cancer Network Guidelines in the absence of data from pediatric-specific surgery trials and/or cohort studies. (3) Accurate classification of ASTs as benign or malignant is more likely with immunohistochemistry and next-generation sequencing. (4) It may not be possible to classify some ASTs as likely/definitively benign or malignant after clinicopathologic and/or molecular correlation, and these Spitz tumors of uncertain malignant potential should be excised with 5 mm margins. (5) ASTs favored to be benign should be excised with 1- to 3-mm margins if transected on biopsy. (6) Re-excision is not necessary if the AST does not extend to the biopsy margin(s) when complete/excisional biopsy was performed. (7) SLNB should not be performed for Spitz tumors unless a diagnosis of CM is favored on clinicopathologic evaluation. (8) Non-Spitz melanocytomas have a presumed increased risk for progression to CM and should be excised with 1- to 3-mm margins if transected on biopsy. (9) Re-excision of non-Spitz melanocytomas is not necessary if the lesion is completely excised on biopsy.

Surgical management of rare tumors (Part 1).

With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers and the Children's Oncology Group fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g., pleuropulmonary blastoma and desmoplastic small round cell tumor) and those that are far more common in adults and therefore rarely studied in children (e.g., thyroid, melanoma, and gastrointestinal stromal tumor). Treatment strategies for these latter tumors are typically based on adult guidelines, although the pediatric variants of these tumors may harbor different genetic signatures and demonstrate different behavior. If melanoma and differentiated thyroid cancer are excluded, other rare cancer types account for only 2% of the cancers in children aged 0 to 14. This article highlights several of the most common rare tumor types.

Current surgical practice for central venous access to deliver chemotherapy and enteral access for nutritional support in pediatric patients with an oncological diagnosis.

Central venous access through tunneled central venous catheters (CVCs) are one of the cornerstones of modern oncologic practice in pediatric patients since CVCs provide a reliable access route for the administration of chemotherapy. Establishing best practices for CVC management in children with cancer is essential to optimize care. This article reviews current best practices, including types of devices, their placement, complications, and long-term outcomes. Additionally, nutrition status and nutritional support are also very important determinants of outcomes and care in pediatric surgical oncology patients. We review current nutritional assessment, support, access for enteral and parenteral nutrition delivery, and their complications, mainly from a surgical perspective. Overall, access surgery, whether for CVCs, or for enteral access can be challenging, and best practice guidelines supported by current though limited evidence are necessary to minimize complications and optimize outcomes.

Classification and Surgical Management of Anorectal Malformations: A Systematic Review and Evidence-based Guideline From the APSA Outcomes and Evidence-based Practice Committee.

OBJECTIVE: Treatment of neonates with anorectal malformations (ARMs) can be challenging due to variability in anatomic definitions, multiple approaches to surgical management, and heterogeneity of reported outcomes. The purpose of this systematic review is to summarize existing evidence, identify treatment controversies, and provide guidelines for perioperative care. METHODS: The American Pediatric Surgical Association Outcomes and Evidence Based Practice Committee (OEBP) drafted five consensus-based questions regarding management of children with ARMs. These questions were related to categorization of ARMs and optimal methods and timing of surgical management. A comprehensive search strategy was performed, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to perform the systematic review to attempt to answer five questions related to surgical care of ARM. RESULTS: A total of 10,843 publications were reviewed, of which 90 were included in final recommendations, and some publications addressed more than one question (question: 1 n = 6, 2 n = 63, n = 15, 4 n = 44). Studies contained largely heterogenous groups of ARMs, making direct comparison for each subtype challenging and therefore, no specific recommendation for optimal surgical approach based on outcomes can be made. Both loop and divided colostomy may be acceptable methods of fecal diversion for patients with a diagnosis of anorectal malformation, however, loop colostomies have higher rates of prolapse in the literature reviewed. In terms of timing of repair, there did not appear to be significant differences in outcomes between early and late repair groups. Clear and uniform definitions are needed in order to ensure similar populations of patients are compared moving forward. Recommendations are provided based primarily on A-D levels of evidence. CONCLUSIONS: Evidence-based best practices for ARMs are lacking for many aspects of care. Multi-institutional registries have made progress to address some of these gaps. Further prospective and comparative studies are needed to improve care and provide consensus guidelines for this complex patient population.

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.

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.

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.

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.

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.

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.

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.

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.

Update on pediatric rhabdomyosarcoma: A report from the APSA Cancer Committee.

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

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).

Minimally invasive surgery for pediatric renal tumors: A systematic review by the APSA Cancer Committee.

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

Minimally invasive surgery for abdominal and thoracic neuroblastic tumors: A systematic review by the APSA Cancer committee.

BACKGROUND: Minimally invasive surgery has broad applicability to pediatric diseases, including pediatric cancer resection. Neuroblastic tumors of childhood are highly variable in presentation, and so careful selection of appropriate candidates for minimally invasive resection is paramount to achieving safe and durable surgical and oncological outcomes. METHODS: The American Pediatric Surgical Association Cancer Committee developed questions seeking to better define the role of minimally invasive surgery for neuroblastic tumors. A search using PubMed, Medline, Embase, Web of Science, ProQuest Dissertations, and Clinical Trials was performed for articles published from 1998 to 2018 in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. RESULTS: The evidence identified is all retrospective in nature. Minimally invasive surgical resection of neuroblastic tumors is safe for carefully selected smaller (4-6 cm) image defined risk factor (IDRF)-negative abdominal tumors when oncologic principles are followed. Size is a less-well defined criterion for thoracic neuroblastic tumors. Open approaches for both abdominal and thoracic tumors may be preferable in the presence of IDRF's. CONCLUSION: Small tumors without IDRF's are reasonable candidates for minimally invasive resection. Surgical oncologic guidelines should be closely followed. The quality of data supporting this systematic review is poor and highlights the need for refinement in the study of such surgical techniques to improve knowledge and outcomes for patients with neuroblastic tumors. TYPE OF STUDY: Systematic Review. LEVEL OF EVIDENCE: Level III and Level IV.

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.

An Evidence-Based Guideline Supporting Restricted Opioid Prescription after Pediatric Appendectomy.

BACKGROUND/PURPOSE: Surgeon overprescription of opioids is a modifiable contributor to the opioid epidemic. No clear guidelines exist for prescribing opioids to younger patients after surgery. We sought to determine postoperative opioid needs in pediatric/young adult patients after laparoscopic appendectomy. METHODS: Patients 5-20 years old who underwent laparoscopic appendectomy were included for study. All consented patients underwent chart review and were additionally called for an attempted interview. Caregivers were queried on analgesic use and adequacy of pain relief. The main outcome measures were: quantity of opioid used, desire for an opioid, presence of pain ≥4/10, and need for follow-up/call owing to pain. All opioids were converted into morphine milligram equivalents (MME). RESULTS: Seventy-three patients qualified for the study, 49 of whom completed a postoperative telephone interview. Of the interviewees, 83% did not use or desire an opioid and reported pain <4/10 after discharge. Five patients used an opioid upon discharge, and the average MME consumed was 23 (equivalent to 3 pills of 5 mg oxycodone). No zero-opioid patients had unanticipated follow-up for pain concerns. CONCLUSIONS: After hospital discharge following laparoscopic appendectomy, most patients have adequate analgesia without opioids. Opioid prescriptions should be offered sparingly and for no more than 25 MME. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Prognosis study.

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.

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.