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.

Management of Pediatric Breast Masses for the Pediatric Surgeon: Expert Consensus Recommendations From the APSA Cancer Committee.

BACKGROUND: The pathology and management of breast masses in pediatric patients is markedly different than in adults. The vast majority of lesions in children and adolescents are benign, but the rare malignant breast masses require prompt recognition and treatment. Pediatric surgeons navigating clinical evaluation of these masses must balance preservation of the developing breast with appropriate diagnosis and surgical management. METHODS: The current English language literature was queried for pediatric and adolescent breast masses. Identified manuscripts were reviewed and classified by level of evidence. Based on these results, as well as expert consensus, an algorithm regarding clinical workup and management was established. RESULTS: Evaluation of pediatric breast masses begins with a thorough history and physical exam. Palpable masses should then be further characterized using an ultrasound-guided algorithm. In select cases, observation without surgical resection is appropriate. Surgical management of presumed benign lesions, when performed, should prioritize conserving developing breast tissue and the nipple areolar complex. Excisional biopsy is preferable to core needle biopsy when technically feasible. Surgical management of malignant lesions varies depending on the type of malignancy. CONCLUSION: Pediatric surgeons are often the first point of contact after identification of a breast mass in a pediatric or adolescent patient, and therefore play a critical role in management. Based on literature review and expert consensus, we propose an algorithm to guide pediatric surgeons in the diagnosis and treatment of these predominantly benign lesions. For the rare malignant lesions, a multi-disciplinary team approach is recommended to optimize patient care.

Assessing the Diagnostic Accuracy of TI-RADS in Pediatric Thyroid Nodules: A Multi-institutional Review.

PURPOSE: Thyroid nodules are uncommon in children and adolescents but carry an increased risk of malignancy when present. The Thyroid Imaging Reporting and Data System (TI-RADS) is an adult-validated ultrasound-based risk assessment providing a prediction of malignant potential for thyroid nodules, thereby guiding recommendations for fine needle aspiration biopsy (FNAB). Minimal data exist regarding the applicability of TI-RADS to predict malignancy in pediatric thyroid nodules. This study aims to analyze the performance of TI-RADS for children and adolescents with thyroid nodules, hypothesizing that applying TI-RADS criteria would improve accuracy and reduce the number of recommended FNAB compared to American Thyroid Association (ATA) size criteria alone. METHODS: A multi-institutional retrospective analysis was conducted including patients ≤21 years with a thyroid nodule by sonographic thyroid imaging between 2015 and 2020. TI-RADS scores were assigned at each institution by a pediatric radiologist trained in thyroid imaging and TI-RADS criteria. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy of TI-RADS scoring were compared to existing ATA size-based recommendation for performing a FNAB. Accounting for relative size differences between adults and children, a novel PED TI-RADS category was developed and tested, recommending FNAB for thyroid nodules with a TI-RADS 3 and ≥ 1.5 cm, TI-RADS 4 and ≥ 1.0 cm, and TI-RADS 5 any feasible size. RESULTS: 291 nodules from 260 patients (median age 14.9 years, 78.8% female) were assessed using TI-RADS. Applying adult TI-RADS criteria resulted in recommendation of FNAB for 35.1% of nodules, in contrast to 76.6% recommended by ATA guidelines (p < 0.0001) (Table). Utilizing the adult TI-RADS score ≥3 as an FNAB indicator resulted in 100% sensitivity and 28.5% specificity, with 0 cases of missed malignant nodules on pathology. When novel PED TI-RADS criteria were applied, 88 patients would have been spared an unnecessary FNAB with improved sensitivity and accuracy over ATA criteria. CONCLUSIONS: The application of adult and PED TI-RADS scoring to thyroid nodules in pediatric patients enhances the accuracy of malignancy prediction compared to current American Thyroid Association size criteria alone. The utilization of PED TI-RADS scoring eliminated unnecessary biopsies in many children while not missing a single thyroid malignancy. LEVEL OF EVIDENCE: Level III.

Robotic-Assisted Versus Laparoscopic Approach for Treatment of Acute Cholecystitis in Children.

Introduction: Laparoscopic cholecystectomy (Lap-C) is the standard of care for patients requiring cholecystectomy in the acute setting. Although robotic-assisted cholecystectomy (RA-C) performance has increased, utilization in the acute setting has not been widely reported. We describe the feasibility of RA-C for pediatric patients undergoing acute inpatient cholecystectomy. Methods: A single institutional retrospective review of patients receiving RA-C while admitted for acute cholecystitis and/or choledocholithiasis (June 2017-June 2022) was compared with a matched cohort who underwent traditional multiport Lap-C (June 2021-June 2022). Demographic, perioperative, and postoperative data were analyzed. Results: Fifty patients were included: 25 each in the RA-C and Lap-C groups. Fifty-four percent were female; 66% were non-Hispanic white. Median age (15.7 years [interquartile range, IQR 14.7, 17.3] versus 15.3 years [IQR 14.5, 16.9], P = .91) and preoperative weight (92.6 kg [IQR 60, 105.9] versus 72.3 kg [IQR 61.6, 85.6], P = .15) were similar between the RA-C and Lap-C groups, respectively. No differences were observed in median operating time (89 minutes [IQR 76, 103] versus 88 minutes [IQR 77, 137], P = .70), postoperative length of stay (22.5 hours [21.4, 24.9] versus 20.6 hours [18.0, 25.1], P = .06), or 30-day complications (12% versus 16%, P = .69). Although opioid utilization (.23 milliequivalents/kilogram [MME/kg] [IQR .03, .30] versus .03 MME/kg [0, .09], P = .02) was higher in the RA-C cohort overall, no differences were detected during an analysis of the most recent 2 years (P = .96). Conclusion: RA-C in the acute setting can be performed safely in the pediatric population with comparable procedural times as well as perioperative and 30-day outcomes.

A Comparison of Commonly Utilized Diagnostic Biopsy Techniques for Pediatric Patients With Cancer: A Systematic Review by the APSA Cancer Committee.

BACKGROUND: Historically, surgical biopsy (SB) for diagnosis of pediatric solid tumors was considered necessary to provide adequate tissue for histologic and molecular analysis. Less invasive biopsy techniques such as image-guided core needle biopsy (CNB), have shown comparable accuracy with decreased morbidity in some adult studies. However, data regarding the safety and efficacy of CNB in pediatric tumors is limited. This study's aim was to assess the overall rate of successful diagnosis and safety of CNB compared to SB in children with malignancies. METHODS: A PRISMA compliant systematic review was performed in MEDLINE via PubMed, Embase and CINAHL Plus database searches from 2010 to 2023. Studies were included with relevance to the following clinical question: For children with concern for malignancy requiring biopsy for diagnosis, how does CNB compare to open or laparoscopic/thoracoscopic SB in terms of safety and diagnostic efficacy? Data for patients ≤21 years requiring biopsy for diagnosis of liver tumors, neuroblastoma (NB), soft tissue sarcoma (STS), and lymphoma were included. RESULTS: Twenty-seven studies including 2477 patients met inclusion criteria, with 2065 undergoing CNB and 412 SB. Of the 2477 patients, 820 patients had NB, 307 liver tumors, 96 STS, 151 lymphoma, and 1103 patients were from studies that included multiple diagnoses. The average complication rate for CNB was 2.9% compared to 21.4% for SB (p < 0.001). Bleeding was the most common complication in both groups, but significantly higher after SB (22.1% vs 2.3%) (p < 0.001). CNB was diagnostic in 90.8% of patients compared to 98.8% who underwent SB (p < 0.001). CONCLUSIONS: Rates of successful diagnosis were greater than 90% for both CNB and SB, though significantly higher for SB. Conversely, complication rates were close to ten times higher after SB compared to CNB. Given its relatively lower risk profile, CNB can be a safe and useful diagnostic tool for children with solid malignancies. Research focused on enhancing CNB's diagnostic accuracy while maintaining low morbidity should be further explored. LEVEL OF EVIDENCE: Treatment study, Level III.

Point-of-Care Lung Ultrasound to Evaluate Lung Isolation During One-Lung Ventilation in Children: A Blinded Observational Feasibility Study.

BACKGROUND: Minimally invasive thoracic surgical techniques require effective lung isolation using one-lung ventilation (OLV). Verification of lung isolation may be confirmed by auscultation, visual confirmation using fiberoptic bronchoscopy (FOB), or more recently, point-of-care ultrasound (POCUS). The aim of this study was to prospectively compare lung ultrasound with clinical auscultation to confirm OLV before thoracic surgery in pediatric patients. METHODS: This prospectively blinded feasibility study included 40 patients ranging in age from 0 to 20 years. After confirmation of lung separation by the primary anesthesia team using FOB, the sonographer and the auscultator, both blinded to the laterality of surgery and lung separation, entered the operating room. The sonographer evaluated for pleural lung sliding and the auscultator listened for breath sounds. Successful lung separation was definitively confirmed by direct visualization of lung collapse during the operation. RESULTS: In confirming effective single-lung ventilation, lung ultrasound had a diagnostic accuracy of 95% (95% confidence interval [CI], 82.7%-98.5%). In contrast, auscultation could only reliably confirm lung isolation with 68% accuracy (95% CI, 51.5%-80.4%). The McNemar test showed a statistically significant difference between the use of lung ultrasound and auscultation (P < .001). The median time to perform ultrasonography was 67 seconds (interquartile range [IQR], 46-142) and the median time to perform auscultation was 21 seconds (IQR, 10-32). CONCLUSIONS: Based on the initial results of our feasibility trial, lung ultrasound proved to be a fast and reliable method to verify single-lung ventilation in pediatric patients presenting for thoracic surgery with a high degree of diagnostic accuracy.

Oncofertility care for children, adolescents, and young adults at risk for treatment-related fertility loss.

As therapy for childhood malignancies becomes more sophisticated and survival has improved, long-term therapy-related sequelae have emerged. Loss of reproductive potential among childhood cancer survivors is one such concern that has become increasingly recognized among patients, families, and healthcare providers. The risk status for infertility based upon therapy received, state of current reproductive technology and outcomes, and an emphasis on adequate referral and counseling for fertility preservation options are reviewed. Contributing factors to infertility are discussed, and options for female and male preservation based upon age and pubertal status are summarized. This article highlights the current state of fertility opportunities for children and adolescents undergoing therapy for cancer. Providers caring for these young patients should be familiar with such options and should routinely initiate evaluations for eligibility of fertility preservation.

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.

Neuroblastoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.

Utilization of a Single-Site Port as an Adjunct for Multi-Port Robotic-Assisted Surgery in Children.

Introduction: The focused use of a single-site port as an adjunct designed to decrease overall port site number and/or assist with specimen extraction in pediatric robotic surgery has not been fully elucidated. We aimed to describe the feasibility of using the single-site port as an adjunct during multi-port robotic-assisted minimally invasive surgery (RA-MIS). Methods: A single institution retrospective review of pediatric patients who underwent multiport RA-MIS with an adjunctive single-site (SS) port from August 2018 to October 2022 was performed. Demographic, perioperative, and postoperative variables were collected; descriptive analysis was performed. Results: A total of 13 patients were included; 46% were female, and 47% were Caucasian. Median age at surgery was 14.9 years of age (interquartile range [IQR] 10.6, 18); median weight was 61.1 kg (IQR 39.7, 73.6). Eleven patients (85%) underwent splenectomy; 2 patients (15%) underwent adrenalectomy. Four patients had a combined procedure (SS cholecystectomy with multi-port splenectomy [n = 3], multi-port bilateral adrenalectomy [n = 1]). The median total operative time was 197 minutes (IQR 131, 316); median console time was 59 minutes (IQR 40, 126). Two 8 mm robotic ports were utilized for all but 1 patient who required a third 8 mm port. The median length of stay was 2.1 days (IQR 2.0, 3.1). One readmission for fever occurred following a combined cholecystectomy/splenectomy. No hernias or wound infections were identified at the single-site port. Conclusion: Use of a SS port as an adjunct is a feasible option and should be considered for those with splenomegaly or need for combined procedures in different quadrants of the abdomen.

Long-term outcomes and patterns of relapse in patients with bilateral Wilms tumor or bilaterally predisposed unilateral Wilms tumor, a report from the COG AREN0534 study.

The objective of this study is to report the long-term timing and patterns of relapse for children enrolled in Children's Oncology Group AREN0534, a multicenter phase III clinical trial conducted from 2009 to 2015. Participants included children with bilateral Wilms tumor (BWT) or unilateral WT with genetic predisposition to develop BWT followed for up to 10 years. Smoothed hazard (risk) functions for event-free survival (EFS) were plotted so that the timing of events could be visualized, both overall and within pre-specified groups. Two hundred and twenty-two children (190 BWT and 32 unilateral WT with BWT predisposition) were followed for a median of 8.6 years. Fifty events were reported, of which 48 were relapse/progression. The overall 8-year EFS was 75% (95% confidence interval: 69%-83%). The highest risk for an EFS event was immediately after diagnosis with a declining rate over 2 years. A second peak of events was observed around 4 years after diagnosis, and a small number of events were reported until the end of the follow-up period. In subset analyses, later increases in risk were more commonly observed in patients with female sex, anaplastic histology, negative lymph nodes or margins, and favorable histology Wilms tumor patients with post-chemotherapy intermediate risk. Among relapses that occurred after 2 years, most were to the kidney. These patterns suggest that late events may be second primary tumors occurring more commonly in females, although more investigation is required. Clinicians may consider observation of patients with BWT beyond 4 years from diagnosis.

Minimally invasive and robotic-assisted approaches applied to pediatric surgical oncology.

The management of pediatric tumors is complex, with surgery, chemotherapy, and radiotherapy being cornerstones in their treatment. Tumor removal is increasingly performed by a minimally invasive approach, which allows for quicker postoperative recovery and less postoperative pain. The goal of this report is to give an overview of minimally invasive surgical approaches for common pediatric tumors, with a focus on technical considerations and postoperative outcomes.

Rare tumors II: Adrenocortical tumors, neuroendocrine tumors of the appendix, pheochromocytoma and paraganglioma, pancreatoblastoma and solid pseudopapillary tumors of the pancreas.

Very rare tumors are usually divided into two groups: One includes tumors that are rare among both children and adults; the other one encompasses tumors that frequently occur in adults but are rarely observed in children. In this review, we focus on adrenocortical tumors, neuroendocrine tumors of the appendix, pheochromocytoma and paraganglioma, pancreatoblastoma and solid pseudopapillary tumors of the pancreas, with special attention to the role of surgery as main curative intervention or as part of the multimodal treatment.

Disease Control and Toxicity Outcomes after Stereotactic Ablative Radiation Therapy for Recurrent and/or Metastatic Cancers in Young-Adult and Pediatric Patients.

BACKGROUND: Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population. METHODS: This was a single-institutional study in patients < 30 years treated with SABR. The primary endpoint was local control (LC), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. The survival analysis was performed using Kaplan-Meier estimates in R v4.2.3. RESULTS: In total, 48 patients receiving 135 SABR courses were included. The median age was 15.6 years (interquartile range, IQR 14-23 y) and the median follow-up was 18.1 months (IQR: 7.7-29.1). The median SABR dose was 30 Gy (IQR 25-35 Gy). The most common primary histologies were Ewing sarcoma (25%), rhabdomyosarcoma (17%), osteosarcoma (13%), and central nervous system (CNS) gliomas (13%). Furthermore, 57% of patients had oligometastatic disease (≤5 lesions) at the time of SABR. The one-year LC, PFS, and OS rates were 94%, 22%, and 70%, respectively. No grade 4 or higher toxicities were observed, while the rates of any grade 1, 2, and 3 toxicities were 11.8%, 3.7%, and 4.4%, respectively. Patients with oligometastatic disease, lung, or brain metastases and those who underwent surgery for a metastatic site had a significantly longer PFS. LC at 1-year was significantly higher for patients with a sarcoma histology (95.7% vs. 86.5%, p = 0.01) and for those who received a biological equivalent dose (BED10) > 48 Gy (100% vs. 91.2%, p = 0.001). CONCLUSIONS: SABR is well tolerated in pediatric patients with 1-year local failure and OS rates of <10% and 70%, respectively. Future studies evaluating SABR in combination with systemic therapy are needed to address progression outside of the irradiated field.

Day to Day Advocacy by Pediatric Health Care Providers.

This manuscript highlights the impressive advocacy work that members of the American Academy of Pediatrics have achieved and serves to inspire pediatric health care providers of all specialties to pursue such efforts beyond the acute physical need of the child. This article represents one of the Symposia presented at the 2023 American Academy of Pediatrics Section on Surgery.

Updates From the Other Side of the Drape: Recent Advances in Multimodal Pain Management and Opioid Reduction Among Pediatric Surgical Patients.

As the management of acute pain for children undergoing surgical procedures as well as recognition of the short and long term risks of exposure to opioids has evolved, multimodal and multidisciplinary approaches using organized pathways has resulted in improved perioperative outcomes and patient satisfaction. In this 2023 symposium held at the American Academy of Pediatrics on Surgery meeting, a multidisciplinary discussion on current enhanced recovery after surgery pathways, alternate methods of effective pain control and education and advocacy efforts for opioid reduction were discussed, and highlights are included in this article.

The Shared Ovary: A Multidisciplinary Discussion With Pediatric and Adolescent Gynecology.

Pediatric and adolescent ovarian lesions are common and are frequently managed by both pediatric surgeons and pediatric and adolescent gynecologists. During the 2023 American Academy of Pediatric Section on Surgery meeting, an educational symposium was delivered focusing on various aspects of management of pediatric and adolescent benign and malignant masses, borderline lesions, and fertility options for children and adolescents undergoing cancer therapies. This article highlights the discussion during this symposium.

Bilateral Wilms tumor with anaplasia: A report from the Children's Oncology Group Study AREN0534.

INTRODUCTION: The purpose of this study is to examine the outcomes in children with anaplastic bilateral Wilms tumor (BWT) from study AREN0534 in order to define potential prognostic factors and areas to target in future clinical trials. METHODS: Demographic and clinical data from AREN0534 study patients with anaplasia (focal anaplasia [FA], or diffuse anaplasia [DA]) were compared. Event-free survival (EFS) and overall survival (OS) were reported using Kaplan-Meier estimation with 95% confidence bands, and differences in outcomes between FA and DA compared using log-rank tests. The impact of margin status was analyzed. RESULTS: Twenty-seven children who enrolled on AREN0534 had evidence of anaplasia (17 DA, 10 FA) in at least one kidney and were included in this analysis. Twenty-six (96%) had BWT. Nineteen percent had anaplastic histology in both kidneys (four of 17 DA, and one of 10 FA). Forty-six percent with BWT had bilateral nephron-sparing surgery (NSS); one child who went off protocol therapy, eventually required bilateral completion nephrectomies. Median follow-up for EFS and OS was 8.6 and 8.7 years from enrollment. Four- and 8-year EFS was 53% [95% confidence interval (CI): 34%-83%] for DA; 4-year EFS was 80% [95% CI: 59%-100%], and 8-year EFS 70% [95% CI: 47%-100%] for FA. Three out of 10 children with FA and eight out of 17 children with DA had events. EFS did not differ statistically by margin status (p = .79; HR = 0.88). Among the six children who died (five DA, one FA), all experienced prior relapse or progression within 18 months. CONCLUSION: Events in children with DA/FA in the setting of BWT occurred early. Caution should be taken about interpreting the impact of margin status outcomes in the context of contemporary multimodal therapy. Future targeted investigations in children with BWT and DA/FA are needed.