Management of Persistent Low-Suspicion Cervical Lymphadenopathy in Pediatric Patients.

INTRODUCTION: Cervical lymphadenopathy in children is typically self-limited; however, the management of persistent lymphadenopathy remains unclear. This study aimed to evaluate the management and outcomes of patients with persistent cervical lymphadenopathy. METHODS: Single-institution, retrospective review of children <18 years undergoing ultrasound (US) for cervical lymphadenopathy from 2013 to 2021 was performed. Patients were stratified into initial biopsy, delayed biopsy, or no biopsy groups. Clinical characteristics and workup were compared, and multivariate analyses were performed to assess predictors of delayed biopsy. RESULTS: 568 patients were identified, with 493 patients having no biopsy, 41 patients undergoing initial biopsy, and 34 patients undergoing delayed biopsy. Presenting symptoms differed: no biopsy patients were younger, were more likely to present to the emergency department, and had clinical findings often associated with acute illness. Patients with USs revealing abnormal vascularity or atypical architecture were more likely to be biopsied. History of malignancy, symptoms >1 week but <3 months, and atypical or change in architecture on US was associated with delayed biopsy. Patients with long-term follow-up (LTF) were followed for a median of 99.0 days. Malignancies were identified in 12 patients (2.1%). All malignancies were diagnosed within 14 days of presentation, and no malignancies were identified in LTF. CONCLUSIONS: Patients with persistent low suspicion lymphadenopathy are often followed for long durations; however, in this cohort, no malignancies were diagnosed during LTF. We propose an algorithm of forgoing a biopsy and employing primary care surveillance and education, which may be appropriate for these patients in the proper setting.

Management of undifferentiated embryonal sarcoma of the liver: A Pediatric Surgical Oncology Research Collaborative study.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare tumor for which there are few evidence-based guidelines. The aim of this study was to define current management strategies and outcomes for these patients using a multi-institutional dataset curated by the Pediatric Surgical Oncology Research Collaborative. METHODS: Data were collected retrospectively for patients with UESL treated across 17 children's hospitals in North America from 1989 to 2019. Factors analyzed included patient and tumor characteristics, PRETEXT group, operative details, and neoadjuvant/adjuvant regimens. Event-free and overall survival (EFS, OS) were the primary and secondary outcomes, respectively. RESULTS: Seventy-eight patients were identified with a median age of 9.9 years [interquartile range [IQR): 7-12]. Twenty-seven patients underwent resection at diagnosis, and 47 patients underwent delayed resection, including eight liver transplants. Neoadjuvant chemotherapy led to a median change in maximum tumor diameter of 1.6 cm [IQR: 0.0-4.4] and greater than 90% tumor necrosis in 79% of the patients undergoing delayed resection. R0 resections were accomplished in 63 patients (81%). Univariate analysis found that metastatic disease impacted OS, and completeness of resection impacted both EFS and OS, while multivariate analysis revealed that R0 resection was associated with decreased expected hazards of experiencing an event [hazard ratio (HR): 0.14, 95% confidence interval (CI): 0.04-0.6]. At a median follow-up of 4 years [IQR: 2-8], the EFS was 70.0% [95% CI: 60%-82%] and OS was 83% [95% CI: 75%-93%]. CONCLUSION: Complete resection is associated with improved survival for patients with UESL. Neoadjuvant chemotherapy causes minimal radiographic response, but significant tumor necrosis.

Survival outcomes in pediatric patients with metastatic Ewing sarcoma who achieve a rapid complete response of pulmonary metastases.

PURPOSE: Our objectives were to compare overall survival (OS) and pulmonary relapse between patients with metastatic Ewing sarcoma (EWS) at diagnosis who achieve rapid complete response (RCR) and those with residual pulmonary nodules after induction chemotherapy (non-RCR). PATIENTS AND METHODS: This retrospective cohort study included children under 20 years with metastatic EWS treated from 2007 to 2020 at 19 institutions in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups. Kaplan-Meier curves were generated for OS and pulmonary relapse. RESULTS: Among 148 patients with metastatic EWS at diagnosis, 61 (41.2%) achieved RCR. Five-year OS was 71.2% for patients who achieved RCR, and 50.2% for those without RCR (p = .04), and in multivariable regression among patients with isolated pulmonary metastases, RCR (hazards ratio [HR] 0.42; 95% confidence interval [CI]: 0.17-0.99) and whole lung irradiation (WLI) (HR 0.35; 95% CI: 0.16-0.77) were associated with improved survival. Pulmonary relapse occurred in 57 (37%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p = .14). Five-year pulmonary relapse rates did not significantly differ based on RCR (33.0%) versus non-RCR (47.0%, p = .13), or WLI (38.8%) versus no WLI (46.0%, p = .32). DISCUSSION: Patients with EWS who had isolated pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse.

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.

Pediatric, Adolescent and Young Adult (AYA) Peritoneal and Pleural Mesothelioma: A National Cancer Database Review.

PURPOSE: Malignant peritoneal and pleural mesothelioma are rare in young patients, with a paucity of data regarding clinical characteristics and outcomes. We aimed to describe the clinical characteristics, treatment strategies, and outcomes for pediatric and adolescent/young adult (AYA) patients. METHODS: The National Cancer Database (NCDB) was queried for malignant peritoneal and pleural mesothelioma in pediatric and AYA patients (ages 0-39) from 2004 to 2019. Stratification was performed for pediatric (age 0-21) and young adult (age 22-39) patients. Chi-squared, multivariable cox regression, and Kaplan-Meier analyses were performed. RESULTS: We identified 570 total patients, 46 pediatric and 524 young adult, with mesothelioma (363 peritoneal and 207 pleural). There were significant differences in sex distribution as patients with peritoneal mesothelioma were more frequently female (63.1%). Patients with peritoneal mesothelioma were more likely to have radical surgery compared to pleural mesothelioma (56.7% v. 24.6%, respectively). A majority of patients with peritoneal and pleural mesothelioma received chemotherapy (66.4% and 61.4%, respectively). For peritoneal mesothelioma, surgical resection was associated with improved overall survival, whereas male sex, neoadjuvant chemotherapy, and radiation were associated with worse overall survival. For pleural mesothelioma, intraoperative chemotherapy was associated with improved overall survival, whereas Black race was associated with worse overall survival. Mean overall survival was greater for patients with peritoneal mesothelioma (125 months) compared to those with pleural mesothelioma (69 months), which remained significant after stratification of pediatric and young adult patients. CONCLUSION: By analyzing a large cohort of pediatric and AYA mesothelioma, this study highlights clinical, prognostic, and survival differences between peritoneal and pleural disease. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Retrospective.

Race and Ethnic Group Enrollment and Outcomes for Wilms Tumor: Analysis of the Current Era Children's Oncology Group Study, AREN03B2.

BACKGROUND: To review race and ethnic group enrollment and outcomes for Wilms tumor (WT) across all 4 risk-assigned therapeutic trials from the current era Children's Oncology Group Renal Tumor Biology and Risk Stratification Protocol, AREN03B2. STUDY DESIGN: For patients with WT enrolled in AREN03B2 (2006 to 2019), disease and biologic features, therapeutic study-specific enrollment, and event-free (EFS) and overall (OS) 4-year survival were compared between institutionally reported race and ethnic groups. RESULTS: Among 5,146 patients with WT, no statistically significant differences were detected between race and ethnic groups regarding subsequent risk-assigned therapeutic study enrollment, disease stage, histology, biologic factors, or overall EFS or OS, except the following variables: Black children were older and had larger tumors at enrollment, whereas Hispanic children had lower rates of diffuse anaplasia WT and loss of heterozygosity at 1p. The only significant difference in EFS or OS between race and ethnic groups was observed among the few children treated for diffuse anaplasia WT with regimen UH-1 and -2 on high-risk protocol, AREN0321. On this therapeutic arm only, Black children showed worse EFS (hazard ratio = 3.18) and OS (hazard ratio = 3.42). However, this finding was not replicated for patients treated with regimen UH-1 and -2 under AREN03B2 but not on AREN0321. CONCLUSIONS: Race and ethnic group enrollment appeared constant across AREN03B2 risk-assigned therapeutic trials. EFS and OS on these therapeutic trials when analyzed together were comparable regarding race and ethnicity. Black children may have experienced worse stage-specific survival when treated with regimen UH-1 and -2 on AREN0321, but this survival gap was not confirmed when analyzing additional high-risk AREN03B2 patients.

Management and Outcomes of Wilms Tumor With Suprarenal Intravascular Extension: A Pediatric Surgical Oncology Research Collaborative Study.

OBJECTIVE: The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms tumor complicated by inferior vena caval thrombus. BACKGROUND: The largest series of these patients was published almost 2 decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients, and outcomes have not been reported. METHODS: Retrospective review of 19 North American centers between 2009 and 2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed. RESULTS: Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and postresection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. The perioperative complication rate was significantly lower after neoadjuvant chemotherapy [(25%) vs upfront surgery (55%); P =0.005]. CPB was not associated with higher complications [CPB (50%) vs no CPB (27%); P =0.08]. Two-year event-free survival was 93% and overall survival was 96%, higher in FH cases (FH 98% vs unfavorable histology/anaplastic 82%; P =0.73). Neither incomplete resection nor viable thrombus cells affected event-free survival or overall survival. CONCLUSIONS: Multimodal therapy resulted in excellent outcomes, even with advanced-stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.

Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: A report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5.

BACKGROUND: Patients with stage IV favorable histology Wilms tumor (FHWT) with extrapulmonary metastases (EPM) constitute a small subset of patients with FHWT. Because of their rarity and heterogeneity, optimal FHWT treatment is not well understood. Children's Oncology Group protocol AREN0533 assigned patients with FHWT and EPM to intensified chemotherapy, regimen M, after initial DD-4A chemotherapy. To improve understanding of prognostic factors and best therapies, experiences of patients with EPM on AREN0533, as well as on protocols AREN03B2 and NWTS-5, were reviewed. METHODS: Combined outcomes for patients with EPM from NWTS-5, AREN0533, and AREN03B2 were determined. Those treated on AREN0533 were compared with those treated on NWTS-5. Prognostic factors were explored in the pooled cohort. RESULTS: Forty-seven patients with FHWT with EPM enrolled on AREN0533, 37 enrolled on NWTS-5, and 64 were followed only on AREN03B2. The pooled cohort of all 148 patients demonstrated a 4-year event-free survival (EFS) of 77.3% (95% CI, 70.8-84.4) and 4-year overall survival of 88.9% (95% CI, 83.9-94.2). Four-year EFS of patients with EPM treated on AREN0533 was 76.0% (95% CI, 64.6-89.4) vs 64.9% (95% CI, 51.7-82.2) on NWTS-5; hazard ratio, 0.64, p = .26; no difference in overall survival was observed. Increasing linear age and slow incomplete lung response were associated with worse EFS in a pooled cohort. CONCLUSIONS: Outcomes for patients with EPM are among the lowest for children with FHWT. Further trials with standardized surgical and radiation treatment to metastatic sites, and prospectively collected biologic and treatment details are needed. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov identifiers: NCT00379340, NCT00898365, and NCT00002611.

Unwrapping Nephrogenic Rests and Nephroblastomatosis for Pediatric Surgeons: A Systematic Review Utilizing the PICO Model by the APSA Cancer Committee.

BACKGROUND: Nephrogenic rests (NR) may represent precursor lesions for Wilms tumor (WT), but their clinical course is not fully understood and no guidelines for treatment exist. This study sought to evaluate the outcomes of pediatric patients with NRs related to traditional chemotherapy and surgery. METHODS: A PRISMA-P-compliant literature search was conducted in MEDLINE, Embase, CINAHL, Web of Science, COCHRANE, and SCOPUS from inception to June 2021. Clinical questions regarding the treatment of NRs, including chemotherapy and surgery, were developed in the population, intervention, comparison, and outcome format. RESULTS: Twenty-five studies including 1445 patients met inclusion criteria for evaluating chemotherapy compared to observation for NRs. Eighteen studies including 1392 patients met inclusion criteria for evaluating the role of surgery for NRs. Patients with isolated NRs who underwent observation progressed to WT 33% of the time; chemotherapy reduced the rate of WT to 3.9%. Observation of multiple NRs and diffuse hyperplastic perilobar nephroblastomatosis (DHPLN) led to progression to WT 50% and 100% of the time, respectively. Chemotherapy reduced the rate of WT to 34% for multiple NRs and 46% for DHPLN. Surgery for isolated NRs reduced the risk of WT development from 23.7% in patients with incomplete excision to 3.3% with complete excision; however, 96% of patients with incompletely excised NRs had bilateral disease. CONCLUSIONS: Observation with close surveillance for isolated NRs is safe. Treatment with chemotherapy is recommended for patients with multiple NRs and DHPLN. Surgical management of NRs should focus on renal function preservation. LEVEL OF EVIDENCE: Treatment study, Level III.

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.

Pediatric Surgeon Perceptions on Operating Room Environmental Stewardship and Current Institutional Climate-Smart Actions.

BACKGROUND: Operating rooms generate significant greenhouse gas emissions. Our objective was to assess current institutional climate-smart actions and pediatric surgeon perceptions regarding environmental stewardship efforts in the operating room. METHODS: A survey was distributed to members of the American Pediatric Surgical Association in June 2022. The survey was piloted among ten general surgery residents and two professional society cohorts of pediatric surgeons. Comparisons were made by demographic and practice characteristics. RESULTS: Survey response rate was 15.9% (n = 160/1009) and included surgeons predominantly from urban (n = 93/122, 76.2%) and academic (n = 84/122, 68.9%) institutions. Only 9.8% (n = 12/122) of pediatric surgeons were currently involved in operating room environmental initiatives. The most common climate-smart actions were reusable materials and equipment (n = 120/159, 75.5%) and reprocessing of medical devices (n = 111/160, 69.4%). Most surgeons either strongly agreed (n = 48/121, 39.7%) or agreed (n = 62/121, 51.2%) that incorporation of environmental stewardship practices at work was important. Surgeons identified reusable materials/equipment (extremely important: n = 61/129, 47.3%, important: n = 38/129, 29.5%) and recycling (extremely important: n = 68/129, 52.7%, important: n = 29/129, 22.5%) as the most important climate-smart actions. Commonly perceived barriers were financial (extremely likely: n = 47/123, 38.2%, likely: n = 50/123, 40.7%) and staff resistance to change (extremely likely: n = 29/123, 23.6%, likely: n = 60/123, 48.8%). Regional differences included low adoption of energy efficiency strategies among respondents from southern states (n = 0/26, p = 0.01) despite high perceived importance relative to other regions (median: 5, IQR: 4-5 vs median: 4, IQR 4-5, p = 0.04). CONCLUSIONS: While most pediatric surgeons agreed that environmental stewardship was important, less than 10% are currently involved in initiatives at their institutions. Opportunities exist for surgical leadership surrounding implementation of climate-smart actions. LEVEL OF EVIDENCE: Level III.

Disparities in care of pediatric, adolescent, and young adult patients with solid tumors: A systematic review.

BACKGROUND: Numerous studies have demonstrated a variety of social inequalities within pediatric and young adult patients with solid tumors. This systematic review examines and consolidates the existing literature regarding disparities in pediatric and young adult solid tumor oncology. PROCEDURE: A MeSH search was performed on the following databases: MEDLINE, PubMed, OvidSP Cochrane, Central, Embase, Cinhal, and Scopus. The systematic review was performed using Rayyan QCRI. RESULTS: Total 387 articles were found on the initial search, and 34 articles were included in final review. Twenty-seven studies addressed racial and ethnic disparities; 23 addressed socioeconomic disparities. Patients with Hispanic ethnicity, Black race, and lower socioeconomic status were more likely to present at later stages, have differences in treatments and higher mortality rates. CONCLUSION: This qualitative systematic review identified both racial and socioeconomic disparities in pediatric cancer patients across a variety of solid tumor types. Patients with Hispanic ethnicity, Black race, and lower socioeconomic status are associated with disparities in stage at presentation, treatment, and outcome. Characterization of existing disparities provides the evidence necessary to support changes at a systemic level.

Nephron sparing surgery and surgical management of intravascular extension of Wilms tumor.

Although general treatment approaches for Wilms tumor differ between Children's Oncology Group and Société Internationale d'Oncologie Pédiatrique-Renal Tumors Study Group protocols, complex tumors that may be candidates for nephron sparing surgery (NSS) and those with intravascular tumor extension represent a management challenge. In both of these scenarios, anatomic considerations are important in guiding management, making these areas of significant similarities in management between the international groups. This paper aims to explore the current approaches to NSS and intravascular tumor extension by both international groups, with attention to the evidence supporting these approaches and current knowledge gaps.

The Utility of Intraoperative Neuromonitoring in Pediatric Surgical Oncology.

BACKGROUND: Intraoperative nerve monitoring (IONM) is a technique used to decrease the possibility of nerve-associated morbidity and damage to nearby neural structures during complex surgical procedures. The use and potential benefits of IONM in pediatric surgical oncology are not well-described. METHODS: An overview of the current literature was performed to elucidate the various techniques that may be useful to pediatric surgeons for resection of solid tumors in children. RESULTS: The physiology and common types of IONM relevant to the pediatric surgeon are described. Important anesthetic considerations are reviewed. Specific applications for IONM that may be useful in pediatric surgical oncology are then summarized, including its use for monitoring the recurrent laryngeal nerve, the facial nerve, the brachial plexus, spinal nerves, and lower extremity nerves. Troubleshooting techniques regarding common pitfalls are then proposed. CONCLUSION: IONM is a technique that may be beneficial in pediatric surgical oncology to minimize nerve injury during extensive tumor resections. This review aimed to elucidate the various techniques available. IONM should be considered as an adjunct for the safe resection of solid tumors in children in the proper setting with the appropriate level of expertise. A multidisciplinary approach is advised. Additional studies are necessary to further clarify the optimal use and outcomes in this patient population. LEVELS OF EVIDENCE: Level III.

Dollars and Sense: The Business of Pediatric Surgery.

INTRODUCTION: This study evaluated North American pediatric surgeons' opinions and knowledge of business and economics in medicine and their perceptions of trends in their healthcare delivery environment. METHODS: We conducted an elective online survey of 1119 American Pediatric Surgical Association members. Over 8 mo, we iteratively developed the survey focused on four areas: opinion, knowledge, current practice environment, and trends in practice environment over the past 5 y. RESULTS: We received 227 (20.3%) complete surveys from pediatric surgeons. One hundred ninety four (85.5%) perceive healthcare as a business and most (85.9%) believe healthcare decisions may affect patients' out-of-pocket expenses. More than half (51.1%) of surgeons believe it has become more challenging to perform emergent cases and most believe staff quality has decreased for elective (56.4%) and emergent (63.0%) cases over the past 5 y. CONCLUSIONS: Pediatric surgeons recognize that medicine is a business and have concerns regarding the decreasing quality of operating room staff and the increasing difficulty providing surgical care over the last 5 y.

Incidence and management of pleural effusions in patients with Wilms tumor: A Pediatric Surgical Oncology Research Collaborative study.

Wilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi-institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P < .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event-free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage-specific treatment regimens.

Histologic type predicts disparate outcomes in pediatric hepatocellular neoplasms: A Pediatric Surgical Oncology Research Collaborative study.

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

Inflammatory myofibroblastic tumor: A multi-institutional study from the Pediatric Surgical Oncology Research Collaborative.

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate malignancy. We describe the largest cohort of IMT patients to date, aiming to further characterize this rare, poorly understood tumor. This is a multi-institutional review of IMT patients ≤39 years, from 2000 to 2018, at 18 hospitals in the Pediatric Surgical Oncology Research Collaborative. One hundred and eighty-two patients were identified with median age of 11 years. Thirty-three percent of tumors were thoracic in origin. Presenting signs/symptoms included pain (29%), respiratory symptoms (25%) and constitutional symptoms (20%). Median tumor size was 3.9 cm. Anaplastic lymphoma kinase (ALK) overexpression was identified in 53% of patients. Seven percent of patients had distant disease at diagnosis. Ninety-one percent of patients underwent resection: 14% received neoadjuvant treatment and 22% adjuvant treatment. Twelve percent of patients received an ALK inhibitor. Sixty-six percent of surgical patients had complete resection, with 20% positive microscopic margins and 14% gross residual disease. Approximately 40% had en bloc resection of involved organs. Median follow-up time was 36 months. Overall 5-year survival was 95% and 5-year event-free survival was 80%. Predictors of recurrence included respiratory symptoms, tumor size and distant disease. Gross or microscopic margins were not associated with recurrence, suggesting that aggressive attempts at resection may not be warranted.

Interhospital variability in localization techniques for small pulmonary nodules in children: A pediatric surgical oncology research collaborative study.

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

Pediatric solid tumors and associated cancer predisposition syndromes: Workup, management, and surveillance. A summary from the APSA Cancer Committee.

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