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Background: Neuroblastoma (NB), the most common extracranial solid tumor in children, is featured by high malignancy and poor prognosis. Flavokawain A (FKA), a novel chalcone isolated from the roots of the kava plant, has been identified to exert the tumor-inhibiting properties in various cancers. The present study was formulated to tell about the anticarcinogenic effects of FKA against NB and to thoroughly elucidate the intrinsic molecular mechanisms. Methods: In this work, for functional experiments, SK-N-SH cells were treated with various concentrations (0, 12.5, 25, 50 μM) of FKA in order to expound the tumor-inhibiting functions of FKA on proliferative ability, clone-forming ability, apoptosis, cell cycle arrest, migratory ability, invasive ability, EMT and in vitro angiogenesis of NB cells. Moreover, to probe into the intrinsic molecular mechanisms underlying the tumor-inhibiting functions of FKA in NB cells, FKA-treated SK-N-SH cells were co-treated with ERK activator LM22B-10 for rescue experiments. Results: In our current work, it was verified that FKA treatment suppressed the proliferative and clone-forming abilities of NB cells, facilitated NB cell apoptosis, arrested NB cell cycle as well as inhibited NB cell migration, invasion, EMT and in vitro angiogenesis in a dose-dependent manner. What's more, molecular docking predicted the compound-protein interaction between FKA and ERK and biotin pull-down assay validated the binding of FKA to ERK. FKA targeted on ERK and acted as an inhibitor of ERK to inactivate ERK/VEGF/MMPs signaling pathway. Treatment with ERK activator LM22B-10 partially abolished the tumor-inhibiting functions of FKA in NB. Conclusion: Overall, FKA may suppress the malignant behaviors of NB cells depending on inactivation of ERK/VEGF/MMPs signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Multiple differentials exist for pediatric liver tumors under 2 years. Accurate imaging diagnosis may obviate the need for tissue sampling in most cases. Objective: To evaluate the imaging features and diagnostic accuracy of computed tomography (CT) in liver tumors in children under 2 years. Methods: Eighty-eight children under 2 years with treatment naive liver neoplasms and baseline contrast-enhanced CT were included in this institutional review board approved retrospective study. Two blinded onco-radiologists assessed these tumors in consensus. Findings assessed included enhancement pattern, lobulated appearance, cystic change, calcifications, central scar-like appearance, and metastases. The radiologists classified the lesion as hepatoblastoma, infantile hemangioma, mesenchymal hamartoma, rhabdoid tumor, or indeterminate, first based purely on imaging and then after alpha-fetoprotein (AFP) correlation. Multivariate analysis and methods of comparing means and frequencies were used for statistical analysis wherever applicable. Diagnostic accuracy, sensitivity, and positive predictive values were analyzed. Results: The mean age of the sample was 11.4 months (95% CI, 10.9–11.8) with 50/88 (57%) boys. The study included 72 hepatoblastomas, 6 hemangiomas, 4 mesenchymal hamartomas, and 6 rhabdoid tumors. Presence of calcifications, multilobular pattern of arterial enhancement, lobulated morphology, and central scar-like appearance was significantly associated with hepatoblastomas (P-value < 0.05). Fourteen out of eighty-eight lesions were called indeterminate based on imaging alone; six lesions remained indeterminate after AFP correlation. Pure radiology-based diagnostic accuracy was 81.8% (95% CI, 72.2–89.2%), which increased to 92.1% (95% CI, 84.3–96.7%) (P-value > 0.05) after AFP correlation, with one hepatoblastoma misdiagnosed as a rhabdoid tumor. If indeterminate lesions were excluded for biopsy, the accuracy would be 98.8% (95% CI, 93.4–99.9%). Conclusion: CT had high accuracy for diagnosing liver neoplasms in the under 2-year age population after AFP correlation. Certain imaging features were significantly associated with the diagnosis of hepatoblastoma. A policy of biopsying only indeterminate lesions after CT and AFP correlation would avoid sampling in the majority of patients. [ABSTRACT FROM AUTHOR]

Neuroblastoma is the most common extracranial solid tumor in children, and a leading cause of childhood cancer deaths. All neuroblastomas arise from neural crest-derived sympathetic neuronal progenitors, but numerous mutations, the most common of which is MYCN amplification, give rise to these lesions. Epigenetic aberrations also play a role in oncogenesis and tumor progression. To better understand biologic diversity of neuroblastomas, we performed joint single-nucleus ATAC sequencing and single-nucleus RNA sequencing on six neuroblastoma cell lines, three of which are MYCN amplified. After standard filtering for high-quality nuclei, we obtained chromatin accessibility and transcript abundance data from 41,733 neuroblastoma tumor cells. Preliminary analysis reveals significant diversity in chromatin landscape and gene expression across neuroblastoma cell lines. This dataset is a valuable resource for studying the transcriptional and epigenetic mechanisms of this deadly childhood disease. [ABSTRACT FROM AUTHOR]

Purpose: Childhood central nervous system (CNS) tumors tend to have a longer time interval until diagnosis than other pediatric malignancies. The aim is to describe the time to diagnosis among Brazilian pediatric patients treated at a tertiary center and explore associated factors. Methods: Cross-sectional study; application of questionnaires to parents of children with CNS tumors during outpatient visit or inpatient care. Results: One hundred parents participated between August and November 2023. The median age of the children at diagnosis was 7.2 years old. Low-grade glioma (LGG) was the most common tumor type (37%), followed by medulloblastoma (24%). The most frequent symptoms were morning and/or persistent vomiting and headache. The mean prediagnostic symptomatic interval (PSI) was 150 days. The mean parental interval was shorter than the medical (58.1 days vs 92.8 days). LGGs and tumors located in the central area had longer intervals to diagnosis than other tumors (296 vs 54 days) (p = 0.005) and (206 vs 155 days) (p = 0.007), respectively. Despite 81% of the patients undergoing pediatric routine follow-up, 87% of them had been diagnosed at an emergency department. Children attended by the same physician had a shorter mean interval (18.2 vs 88.3 days) than those assisted by different professionals (p = 0.015). The mean time for referral to our specialized center was 23 days. Conclusions: This study is a crucial step in recognizing barriers to early diagnosis of CNS tumors in a middle-income country as low awareness of signs/symptoms by parents and health professionals, aiming to provide opportunities for intervention strategies to reduce the time to diagnosis. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma is the most common extracranial solid tumor in children and accounts for 15% of pediatric cancer related deaths. Targeting neuroblastoma with immunotherapies has proven challenging due to a paucity of immune cells in the tumor microenvironment and the release of immunosuppressive cytokines by neuroblastoma tumor cells. We hypothesized that combining an oncolytic Herpes Simplex Virus (oHSV) with natural killer (NK) cells might overcome these barriers and incite tumor cell death. Methods: We utilized MYCN amplified and non-amplified neuroblastoma cell lines, the IL-12 expressing oHSV, M002, and the human NK cell line, NK-92 MI. We assessed the cytotoxicity of NK cells against neuroblastoma with and without M002 infection, the effects of M002 on NK cell priming, and the impact of M002 and priming on the migratory capacity and CD107a expression of NK cells. To test clinical applicability, we then investigated the effects of M002 and NK cells on neuroblastoma in vivo. Results: NK cells were more attracted to neuroblastoma cells that were infected with M002. There was an increase in neuroblastoma cell death with the combination treatment of M002 and NK cells both in vitro and in vivo. Priming the NK cells enhanced their cytotoxicity, migratory capacity and CD107a expression. Conclusions: To the best of our knowledge, these investigations are the first to demonstrate the effects of an oncolytic virus combined with self-maintaining NK cells in neuroblastoma and the priming effect of neuroblastoma on NK cells. The current studies provide a deeper understanding of the relation between NK cells and neuroblastoma and these data suggest that oHSV increases NK cell cytotoxicity towards neuroblastoma. [ABSTRACT FROM AUTHOR]

Incidental brain tumor findings in children involve the unexpected discovery of brain lesions during imaging for unrelated reasons. These findings differ significantly from those in adults, requiring a focus on pediatric-specific approaches in neurosurgery, neuroimaging, and neuro-oncology. Understanding the prevalence, progression, and management of these incidentalomas is crucial for informed decision-making, balancing patient welfare with the risks and benefits of intervention. Incidental brain tumors are observed in about 0.04–5.7% of cases, with most suspected low-grade lesions in children showing a benign course, though up to 3% may undergo malignant transformation. Treatment decisions are influenced by factors such as patient age, tumor characteristics, and family anxiety, with conservative management through surveillance often preferred. However, upfront surgery may be considered in cases with low surgical risk. Initial follow-up typically involves a comprehensive MRI after three months, with subsequent scans spaced out if the lesion remains stable. Changes in imaging or symptoms during follow-up could indicate malignant transformation, prompting consideration of surgery or biopsy. Several challenges and controversies persist, including the role of upfront biopsy for molecular profiling, the use of advanced imaging techniques like PET-CT and magnetic resonance spectroscopy, and the implications of the child's age at diagnosis. These issues highlight the need for further research to guide management and improve outcomes in pediatric patients with incidental brain tumor findings. [ABSTRACT FROM AUTHOR]

Background: Low-grade glioma is the most common brain tumor in children with different modes of treatment and a high overall survival. Low-grade glioma is considered a chronic disease, since residual tumor is present in many children. The tumor and its treatment lead to acquired brain injury with diverse consequences for later life based on factors like the diverse tumor locations, treatment(s) applied, neurofibromatosis type 1, and age at diagnosis. Methods: An overview of affected domains is provided based upon cohort studies from literature and partially based on clinical experience with a practical approach regarding each domain of functioning in order to provide insight in the requirements for long-term care assistance after childhood low-grade glioma. Results: The diverse domains that can potentially be affected are described as follows: motor function, speech, eating and swallowing, sensory functions, seizures, neuropathy, organ function after systemic treatment, late effects due to cranial radiation (vascular changes and secondary tumors, endocrine and hypothalamic function, sleep and energy, neuro-cognition and education, psychosocial effects, and quality of life. Conclusion: Insight in affected domains guides advices for medical follow-up, diagnostics, supportive instructions, and assistive measures per domain of functioning and provide insight in the requirements for long-term care assistance after childhood low-grade glioma. [ABSTRACT FROM AUTHOR]

Purpose: Pediatric low-grade gliomas (pLGG) are the most common brain tumors in children and achieving complete resection (CR) in pLGG is the most important prognostic factor. There are multiple intraoperative tools to optimize the extent of resection (EOR). This article investigates and discusses the role of intraoperative ultrasound (iUS) and intraoperative magnetic resonance imaging (iMRI) in the surgical treatment of pLGG. Methods: The tumor registries at Tuebingen, Rome and Pretoria were searched for pLGG with the use of iUS and data on EOR. The tumor registries at Liverpool and Tuebingen were searched for pLGG with the use of iMRI where preoperative CR was the surgical intent. Different iUS and iMRI machines were used in the 4 centers. Results: We included 111 operations which used iUS and 182 operations using iMRI. Both modalities facilitated intended CR in hemispheric supra- and infratentorial location in almost all cases. In more deep-seated tumor location like supratentorial midline tumors, iMRI has advantages over iUS to visualize residual tumor. Functional limitations limiting CR arising from eloquent involved or neighboring brain tissue apply to both modalities in the same way. In the long-term follow-up, both iUS and iMRI show that achieving a complete resection on intraoperative imaging significantly lowers recurrence of disease (chi-square test, p < 0.01). Conclusion: iUS and iMRI have specific pros and cons, but both have been proven to improve achieving CR in pLGG. Due to advances in image quality, cost- and time-efficiency, and efforts to improve the user interface, iUS has emerged as the most accessible surgical adjunct to date to aid and guide tumor resection. Since the EOR has the most important effect on long-term outcome and disease control of pLGG in most locations, we strongly recommend taking all possible efforts to use iUS in any surgery, independent of intended resection extent and iMRI if locally available. [ABSTRACT FROM AUTHOR]

Pediatric low-grade gliomas (pLGGs) are the most common brain tumor types affecting children. Although gross-total resection remains the treatment of choice, many tumors are not amenable to complete removal, because they either involve midline structures, such as the optic chiasm or hypothalamus, and are not conducive to aggressive resection, or have diffuse biological features and blend with the surrounding brain. Historically, radiation therapy was used as the second-line option for disease control, but with the recognition that this often led to adverse long-term sequelae, particularly in young children, conventional chemotherapy assumed a greater role in initial therapy for unresectable tumors. A variety of agents demonstrated activity, but long-term disease control was suboptimal, with more than 50% of tumors exhibiting disease progression within 5 years. More recently, it has been recognized that a high percentage of these tumors in children exhibit constitutive activation of the mitogen-activated protein kinase (MAPK) pathway because of BRAF translocations or mutations, NFI mutations, or a host of other anomalies that converged on MAPK. This led to phase 1, 2, and 3 trials that explored the activity of blocking this signaling pathway, and the efficacy of this approach compared to conventional chemotherapy. Despite initial promise of these strategies, not all children tolerate this therapy, and many tumors resume growth once MAPK inhibition is stopped, raising concern that long-term and potentially life-long treatment will be required to maintain tumor control, even among responders. This observation has led to interest in other treatments, such as immunotherapy, that may delay or avoid the need for additional treatments. This chapter will summarize the place of immunotherapy in the current armamentarium for these tumors and discuss prior results and future options to improve disease control, with a focus on our prior efforts and experience in this field. [ABSTRACT FROM AUTHOR]

Purpose: Low-grade glioma is the most common brain tumor among children and adolescents. When these tumors arise in the temporal lobe, patients frequently present with seizures that are poorly controlled with antiepileptic drugs. Here we summarize the clinical features, pathophysiology, preoperative evaluation, surgical treatment, and outcomes of pediatric patients with low-grade gliomas in the temporal lobe. Methods: We reviewed the literature on pediatric low-grade gliomas in the temporal lobe, focusing on cohort studies and systematic reviews that described surgical treatment strategies and reported both oncologic and epilepsy outcomes. Results: The differential diagnoses of pediatric low-grade gliomas in the temporal lobe include ganglioglioma, dysembryoplastic neuroepithelial tumor, desmoplastic infantile ganglioglioma, papillary glioneuronal tumor, pilocytic astrocytoma, pleomorphic xanthoastrocytoma, angiocentric glioma, and polymorphous low-grade neuroepithelial tumor of the young. There is no consensus on the optimal surgical approach for these tumors: lesionectomy alone, or extended lesionectomy with anterior temporal lobectomy, with or without removal of mesial temporal structures. Gross total resection and shorter preoperative duration of epilepsy are strongly associated with favorable seizure outcomes, defined as Engel Class I or Class II, approaching 90% in most series. The risk of surgical complications ranges from 4 to 17%, outweighing the lifetime risks of medically refractory epilepsy. Conclusion: Pediatric patients with temporal low-grade glioma and tumor-related epilepsy are best managed by a multidisciplinary epilepsy surgery team. Early and appropriate surgery leads to prolonged survival and a greater likelihood of seizure freedom, improving their overall quality of life. [ABSTRACT FROM AUTHOR]

Pediatric-type low-grade glioma (PLGG) encompasses a heterogeneous group of WHO grade 1 or 2 tumors and is the most common central nervous system tumor found in children. PLGG extends beyond pediatrics, into adolescents and young adults (AYA, ages 15–40). PLGG represents 25% of all gliomas diagnosed in AYA with differences in tumor location and molecular alterations compared to children, resulting in improved outcome for AYAs. Long-term outcome is excellent, though patients may suffer significant morbidity depending on tumor location. There are differences in treatment practices with radiation used to treat PLGG in AYAs more often than in children. Most PLGG in AYA harbor an alteration in the RAS/MAPK pathway, with limited insight into response to targeted therapy in this age group. This review discusses the epidemiology, current therapeutic approaches, and challenges in the management of PLGG in AYA. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome characterized by the development of both central and peripheral nervous system tumors. Low-grade glioma (LGG) is the most prevalent central nervous system tumor occurring in children with NF1, arising most frequently within the optic pathway, followed by the brainstem. Historically, treatment of NF1-LGG has been limited to conventional cytotoxic chemotherapy and surgery. Despite treatment with chemotherapy, a subset of children with NF1-LGG fail initial therapy, have a continued decline in function, or recur. The recent development of several preclinical models has allowed for the identification of novel, molecularly targeted therapies. At present, exploration of these novel precision-based therapies is ongoing in the preclinical setting and through larger, collaborative clinical trials. Herein, we review the approach to surveillance and management of NF1-LGG in children and discuss upcoming novel therapies and treatment protocols. [ABSTRACT FROM AUTHOR]

This study aimed to determine the predictive power of religious coping of parents of children with cancer on caregiver burden, depression, anxiety, and stress in Turkey. It was designed as a descriptive and cross-sectional study, utilizing correlational analysis and regression models to explore associations between variables. Data were collected from 164 parents in the pediatric hematology-oncology clinics of a university hospital between November 2023 and March 2024. There was a negative correlation between caregiver burden score and negative and positive religious coping scores. Caregiver burden scores were positively correlated with depression, anxiety, and stress scores. Results indicated that caregiver burden, education level, employment status, family structure, family income, and age at diagnosis significantly predicted positive religious coping. For negative religious coping, caregiver burden, education level, family structure, and family income were significant predictors. This suggests that religious coping may help reduce caregiver burden, underscoring the importance of promoting constructive coping strategies to support caregivers' well-being. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Conventional chemotherapy remains unsatisfactory due to drug toxicity and resistance issues. Therefore, there is an urgent need to develop more effective treatments for advanced osteosarcoma. In the current study, we focused on evaluating the anticancer efficacy of avermectin B1, a novel avermectin analog, against osteosarcoma cells. Methods: The half-inhibitory concentration of avermectin B1 was calculated in three osteosarcoma cell lines. Then, functional experiments were conducted to evaluate the effects of avermectin B1 on cell proliferation, the cell cycle, apoptosis and autophagy. Moreover, the AMPK/ULK1 signaling pathway was detected by Western blot assay. Finally, the in vivo effect of avermectin B1 on tumor growth and metastasis was investigated using the xenograft mouse model. To examine the role of the AMPK/ULK1 pathway, an AMPK-specific inhibitor (dorsomorphin) was used in combination with avermectin B1. Results: Avermectin B1 inhibited the proliferation of osteosarcoma cells in a dose-dependent manner based on CCK8 and colony formation assays. Then, it was found to inhibit migration and invasion by wound healing assay and cell migration and invasion assay. In addition, avermectin B1 induced osteosarcoma cell apoptosis and autophagy. In vivo, avermectin B1 effectively inhibited osteosarcoma cell growth and pulmonary metastasis. Mechanistically, avermectin B1 activated the AMPK/ULK1 pathway to exert antitumor activity in vitro and in vivo. Dorsomorphin significantly attenuated the Avermectin B1-induced antitumor activities. Conclusion: Our study suggests that avermectin B1 is a potential agent to treat osteosarcoma cells through the AMPK/ULK1 signaling pathway. [ABSTRACT FROM AUTHOR]

Pancreatic masses are extremely rare in pediatric patients, with limited data available. This lack of data makes the diagnosis and management of these tumors in children extremely challenging. Therefore, we aimed to describe the presentations, clinical course, and outcomes of children with pancreatic tumors at our center. A retrospective analysis was performed of all pediatric patients diagnosed with pancreatic masses between 2003 and 2022 in an academic freestanding children's hospital. Data including demographics, clinical presentation, workup, management, and subsequent morbidity and mortality were collected and aggregated. Furthermore, we reviewed cases of pancreatic tumor resections in the National Surgical Quality Improvement Program – Pediatric (NSQIP-P) database to identify common adverse outcomes and measures for quality improvement. In total, 17 patients were identified at our institution. Diagnoses included solid pseudopapillary (n = 9), gastrinoma (n = 1), rhabdomyosarcoma (n = 2), pancreatoblastoma (n = 2), and insulinoma (n = 1). Two patients did not have a histopathologic diagnosis and were excluded from subsequent analysis. Overall, 12 patients underwent surgical intervention, with the most common procedures being pancreaticoduodenectomy and distal pancreatectomy, and all 12 were known to be alive at last contact. There were 3 deaths, all due to complications related to metastatic disease. Furthermore, 30-day postoperative outcomes in the NSQIP-P dataset for pancreatic surgeries in pediatric patients are excellent, with negligible morbidity and no mortalities after the index surgery. Conclusions: Children with pancreatic tumors amenable to surgical resection appear to have adequate long-term survival. Short-term outcomes at diagnosis are excellent and mainly appear to be influenced by the presence of metastatic disease at initial presentation. What is Known: • Pancreatic masses are a rare entity in children with limited data on their presentation, management and surgical outcomes. • Solid Pseudopapillary tumors are one of the most common pancreatic tumors in children with a fair prognosis after surgical intervention. What is New: • Surgical management of pediatric patients with pancreatic tumors is safe and effective in patients who do not have aggressive tumor types or metastatic disease. • Our case series provides a notable cohort of these pancreatic tumors with insight into the presentation, management and outcomes of five of these tumor types. [ABSTRACT FROM AUTHOR]

Purpose We aimed to document the acceptability (enrollment rate) and feasibility (phone call delivery rate) of implementing a behavioral PA intervention over 12 weeks, in addition to documenting its effects on patient-reported outcomes and physical functioning. This study also describes the costs of carrying out a behavioral PA intervention. A total of 40 participants were randomized in a 1:1 ratio. The tailored behavioral PA intervention was developed based on the most recent PA guidelines in pediatric oncology and on the COM-B framework to enact PA behavior changes. The prescription (frequency, intensity, time and type (FITT)) was adjusted each week during the weekly support calls. The control group did not receive the intervention. 26 males and 14 females (13.6 years old on average and 2.9 years post-cancer treatment on average) participated in our study. The acceptability rate was 90.9% and the feasibility rate was > 85%. We found that 85% improved PA frequency, 80% improved PA intensity, 100% improved PA time, and 50.0% achieved the recommended PA guidelines. No adverse events were reported over the duration of the intervention. Physical function improved with longer 6-minute walk distances in the intervention group (465.8 ± 74.5 m) than in the control group (398.7 ± 92.9 m) (p = 0.016). PROs scores for all participants were within the limits of the normal range. The estimated cost per participant of carrying out this intervention was USD $126.57. Our 12-week behavioral PA intervention, based on the COM-B framework, was found to be acceptable, feasible and safe in childhood cancer survivors. This study is an important step in the right direction to make exercise standard practice in pediatric oncology. Clinical trial registration: NCT04947709. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma (NB) is one of the most frequent parenchymal tumors among children, with a high degree of heterogeneity and wide variation in clinical presentation. Despite significant therapeutic advances in recent years, long-term survival in high-risk patients remains low, emphasizing the urgent need to find new biomarkers and construct reliable prognostic models. Methods: In this study, data from neuroblastoma samples in the ArrayExpress database were utilized to identify key gene modules and pivotal genes associated with NB prognosis by weighted gene co-expression network analysis (WGCNA). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis was performed using the DAVID database. Based on these hub genes, survival prognosis models were constructed and validated on an independent validation set in the Gene Expression Omnibus (GEO) database. Differences in biological functions and immune microenvironments and the sensitivity to pharmacological and immunotherapeutic treatments of patients in the high- and low-risk groups were examined by gene set enrichment analysis (GSEA) and immune infiltration analysis. Results: WGCNA identified 14 gene modules and screened the module with the highest relevance to the International Neuroblastoma Staging System (INSS), containing 60 pivotal genes. GO and KEGG analyses demonstrated that these pivotal genes were mainly implicated in biological processes and signaling pathways including DNA replication, cell division, mitotic cell cycle, and cell cycle. Based on Lasso regression and COX regression analysis, a prognostic model containing DHFR, GMPS and E2F3 was constructed, and the RiskScore was significantly correlated with the 1-, 3- and 5-year survival of the patients. GSEA and immune infiltration analyses revealed significant differences in the levels of cell cycle-related pathways and immune cell infiltration between the high and low RiskScore groups. In particular, patients in the high-risk group are less likely to benefit from immunotherapy and may be better suited for treatment with drugs such as Oxaliplatin and Alpelisib. Conclusion: This research systematically identified biomarkers related to NB prognosis and developed a reliable prognostic model applying WGCNA and multiple bioinformatics methods. The model has important application value in predicting patients' prognosis, evaluating drug sensitivity and immunotherapy effect, and provides new ideas and directions for precise treatment of neuroblastoma. [ABSTRACT FROM AUTHOR]

Purpose: Various surgical nuances of the telovelar approach have been suggested. The necessity of removing the posterior arch of C1 to accomplish optimal tumor exposure is still debated. Therefore, we report on our experience and technical details of the fourth ventricular tumor resection in a modified prone position without systematic removal of the posterior arch of C1. Methods: A retrospective analysis of all pediatric patients, who underwent a fourth ventricular tumor resection in the modified prone position between 2012 and 2021, was performed. Results: We identified 40 patients with a median age of 6 years and a M:F ratio of 25:15. A telovelar approach was performed in all cases. In 39/40 patients, the posterior arch of C1 was not removed. In the remaining patient, the reason for removing C1 was tumor extension below the level of C2 with ventral extension. Gross or near total resection could be achieved in 34/39 patients, and subtotal resection in 5/39 patients. In none of the patients, a limited exposure, sight of view, or range of motion caused by the posterior arch of C1 was encountered, necessitating an unplanned removal of the posterior arch of C1. Importantly, in none of the cases, the surgeon had the impression of a limited sight of view to the most rostral parts of the fourth ventricle, which necessitated a vermian incision. Conclusion: A telovelar approach without the removal of the posterior arch of C1 allows for an optimal exposure of the fourth ventricle provided that critical nuances in patient positioning are considered. [ABSTRACT FROM AUTHOR]

Background: Ewing sarcoma (ES) is the second most common primary malignant bone tumor in children and adolescents. Despite more intensive chemotherapy regimens and improved local control therapy, there is still a considerable rate of recurrent/progressive disease. Methods: A retrospective study of 50 relapsed/progressive ES patients who were treated at the National Cancer Institute (NCI), Cairo University, during the period from 1st of January 2008 to the end of December 2018, to assess different prognostic variables and disease outcomes. Results: Out of fifty eligible cases, 32 patients (64%) had disease recurrence, and 18 (36%) developed disease progression on treatment. The median follow-up period was 7.4 months. The median overall survival (OS) was 7.5 months, and the cumulative OS was 64% at 6 months and 32.6% at 1 year. The cumulative event-free survival (EFS) was 41.3% at 6 months and 22.3% at 1 year. Patients with disease recurrence had better OS and EFS than patients with disease progression (p = 0.019). Patients who underwent local control at relapse/progression had a significantly better outcome than patients who received chemotherapy only (p < 0.001). Recurrence > 2 years from initial diagnosis was the only independent predictor of better survival outcome. Conclusions: Patients with relapsing/progressive ES portended a poor outcome, with disease progression on treatment faring worse than relapse. Better outcome was observed in patients who experienced recurrence > 2 years after diagnosis, patients with disease recurrence rather than disease progression on treatment, and patients who underwent local control along with intensive chemotherapy. [ABSTRACT FROM AUTHOR]

Neuroblastoma, the deadliest solid tumor in children, exhibits alarming mortality rates, particularly among high-risk cases. To enhance survival rates, a more precise risk stratification for patients is imperative. Utilizing proteomic data from 34 cases with or without N-Myc amplification, we identified 28 differentially expressed ubiquitination-related proteins (URGs). From these, a prognostic signature comprising 6 URGs was constructed. A nomogram incorporating clinical-pathological parameters yielded impressive AUC values of 0.88, 0.93, and 0.95 at 1, 3, and 5 years, respectively. Functional experiments targeting the E3 ubiquitin ligase FBXO42, a component of the prognostic signature, revealed its TP53-dependent promotion of neuroblastoma cell proliferation. In conclusion, our ubiquitination-related prognostic model robustly predicts patient outcomes, guiding clinical decisions. Additionally, the newfound pro-proliferative role of FBXO42 offers a novel foundation for understanding the molecular mechanisms of neuroblastoma. [ABSTRACT FROM AUTHOR]

Purpose: Pediatric spinal cord gliomas (PSGs) are rare in children and few reports detail their imaging features. We tested the association of tumoral grade with imaging features and proposed a novel approach to categorize post-contrast enhancement patterns in PSGs. Methods: This single-center, retrospective study included patients <21 years of age with preoperative spinal MRI and confirmed pathological diagnosis of PSG from 2000-2022. Tumors were classified using the 5th edition of the WHO CNS Tumors Classification. Two radiologists reviewed multiple imaging features, and classified enhancement patterns using a novel approach. Fisher's exact test determined associations between imaging and histological features. Results: Forty-one PSGs were reviewed. Thirty-four were intramedullary, and seven were extramedullary. Pilocytic astrocytoma was the most common tumor (39.02%). Pain and weakness were the most prevalent symptoms. Seven patients (17.07%) died. Cyst, syringomyelia, and leptomeningeal enhancement were associated with tumor grade. Widening of the spinal canal was observed only in low-grade astrocytomas. There was a significant association between tumor grade and contrast enhancement pattern. Specifically, low-grade PSGs were more likely to exhibit type 1A enhancement (mass-like, with well-defined enhancing margins) and less likely to exhibit type 1B enhancement (mass-like, with ill-defined enhancing margins). Conclusion: PSGs display overlapping imaging features, making grade differentiation challenging based solely on imaging. The correlation between tumor grade and contrast enhancement patterns suggests a potential diagnostic avenue, requiring further validation with larger, multicenter studies. Furthermore, Low-grade PSGs display cysts and syringomyelia more frequently, and leptomeningeal enhancement is less common. [ABSTRACT FROM AUTHOR]

This study explores migrasomes' role in neuroblastoma, a common malignant tumor in children, and their potential impact on tumor formation. We analyzed neuroblastoma RNA-seq datasets from public databases, including GSE62564, GSE181559, target, and fwr144. Through data normalization and unsupervised classification using migrasome-specific molecular markers, Differentially Expressed Genes were identified, followed by functional enrichment analysis. Our novel migrasome-associated machine learning model, MigScore, was developed using ten algorithms and 101 combinations, validated on two single-cell datasets. This enabled immune infiltration assessment and drug compatibility prediction, highlighting the utility of MS275, a histone deacetylase inhibitor. Results showed a significant inverse relationship between MigScore and favorable clinical outcomes, elucidating the link between migrasome pathways and tumor immunogenicity. These findings suggest that migrasomes are crucial in neuroblastoma prognosis, leading to the possibility of personalized treatment strategies and improved outcomes. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is the most common and deadliest extracranial solid tumor in children. Targeting tumor-associated macrophages (TAMs) is a strategy for attenuating tumor-promoting states. The crosstalk between cancer cells and TAMs plays a pivotal role in mediating tumor progression in NB. The overexpression of Hexokinase-3 (HK3), a pivotal enzyme in glucose metabolism, has been associated with poor prognosis in NB patients. Furthermore, it correlates with the infiltration of M2-like macrophages within NB tumors, indicating its significant involvement in tumor progression. Therefore, HK3 not only directly regulates the malignant biological behaviors of tumor cells, such as proliferation, migration, and invasion, but also recruits and polarizes M2-like macrophages through the PI3K/AKT-CXCL14 axis in neuroblastoma. The secretion of lactate and histone lactylation alterations within tumor cells accompanies this interaction. Additionally, elevated expression of HK3 in M2-TAMs was found at the same time. Modulating HK3 within M2-TAMs alters the biological behavior of tumor cells, as demonstrated by our in vitro studies. This study highlights the pivotal role of HK3 in the progression of NB malignancy and its intricate regulatory network with M2-TAMs. It establishes HK3 as a promising dual-functional biomarker and therapeutic target in combating neuroblastoma. [ABSTRACT FROM AUTHOR]

Tumor lysis syndrome (TLS) is a life-threatening metabolic disorder caused by massive tumor lysis. Allopurinol, a xanthine oxidase inhibitor, is initiated during chemotherapy to prevent hyperuricemia and subsequent acute kidney injury (AKI). We report two cases of xanthine nephrolithiasis during TLS in newly diagnosed hematologic malignancy patients receiving prophylactic allopurinol. Allopurinol use likely promoted xanthine crystallization, stone formation, and AKI. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of pediatric Wilms' tumor (WT) is high in Africa, though patients abandon treatment after initial diagnosis. We sought to identify factors associated with WT treatment abandonment in Uganda. Methods: A cohort study of patients < 18 years with WT in a Ugandan national referral hospital examined clinical and treatment outcomes data, comparing children whose families adhered to and abandoned treatment. Abandonment was defined as the inability to complete neoadjuvant chemotherapy and surgery for patients with unilateral WT and definitive chemotherapy for patients with bilateral WT. Patient factors were assessed via bivariate logistic regression. Results: 137 WT patients were included from 2012 to 2017. The mean age was 3.9 years, 71% (n = 98) were stage III or higher. After diagnosis, 86% (n = 118) started neoadjuvant chemotherapy, 59% (n = 82) completed neoadjuvant therapy, and 55% (n = 75) adhered to treatment through surgery. Treatment abandonment was associated with poor chemotherapy response (odds ratio [OR] 4.70, 95% confidence interval [CI] 1.30–17.0) and tumor size > 25 cm (OR 2.67, 95% CI 1.05–6.81). Conclusions: Children with WT in Uganda frequently abandon care during neoadjuvant therapy, particularly those with large tumors with poor response. Further investigation into the factors that influence treatment abandonment and a deeper understanding of tumor biology are needed to improve treatment adherence of children with WT in Uganda. [ABSTRACT FROM AUTHOR]

Background: Chordomas are rare, malignant tumors typically centered in midline structures such as the clivus and sacrum, with peak prevalence in the fourth decade. Clival chordomas may secondarily extend to involve the nasopharynx and nasal cavity; however, primary extra-osseous chordomas are even more uncommon. We present an unusual case of a primary sinonasal chondroid chordoma arising from the maxillary sinus in a 5-year-old child. This is the second case of primary sinonasal chordoma reported in the literature so far, after Tao ZZ et al. and the first case of the chondroid variant. Case presentation: A 5-year-old male presented with right-sided nasal obstruction, nasal congestion, and snoring for 2 months. Physical examination showed a reddish polypoidal mass in the right nasal cavity obstructing the choana with nasal septal deviation toward left side. Radiological examination with CT confirmed the presence of a well-defined, heterogeneously hyperdense lobulated mass in right maxillary sinus extending into right nasal cavity with intralesional coarse calcifications. MRI revealed expansile solid altered signal intensity mass, which appears to be isointense on T1-weighted imaging (T1WI) and heterogeneously hyperintense on T2-weighted imaging (T2WI) with a heterogeneous honeycomb pattern of enhancement. Differentials considered were rhabdomyosarcoma, nasopharyngeal carcinoma, and neuroblastoma metastasis. However, the lesion was pathologically proven as a chondroid chordoma. No association with skull base or clival lesion was found on review. Conclusions: Primary sinonasal chordomas are rare in occurrence but should be considered a differential for sinonasal masses in the presence of characteristic MRI features, despite their uncommon location. [ABSTRACT FROM AUTHOR]

The experience of childhood cancer (CC) could be a traumatic event that produces long-term emotional responses such as posttraumatic stress symptoms (PTSS) and posttraumatic growth (PTG) in survivors. The relationship between both PTSS and PTG is not clear in CC survivors. Assessing challenges to core beliefs and rumination could give information regarding the different paths that lead to traumatic responses. Thus, this study aims to identify childhood cancer survivors' profiles from PTSS and PTG measures and to examine the pathways of relationships between PTSS and PTG, rumination, and challenge to core belief. Sixty-two CC survivors completed surveys on their childhood cancer experience, PTSS, PTG, challenge to core beliefs, and rumination. High PTG scores among childhood cancer survivors (Cluster 1), High PTSS scores among childhood cancer survivors (Cluster 2), and Childhood cancer survivors without changes (Cluster 3). Network analysis found that the challenge to core beliefs is the central point in the relationship between the variables, in a direct and positive relationship with PTG. We found an indirect path from challenge to core beliefs to PTSS, mediated by intrusive and deliberative ruminations. The combined findings suggested that there are different profiles related to trauma in CC survivors and the relationship between PTSS and PTG is mediated by the challenge to core beliefs and deliberative and intrusive rumination. [ABSTRACT FROM AUTHOR]

Pediatric gliomas, consisting of both pediatric low-grade (pLGG) and high-grade gliomas (pHGG), are the most frequently occurring brain tumors in children. Over the last decade, several milestone advancements in treatments have been achieved as a result of stronger understanding of the molecular biology behind these tumors. This review provides an overview of pLGG and pHGG highlighting their clinical presentation, molecular characteristics, and latest advancements in therapeutic treatments. Conclusion: The increasing understanding of the molecular biology characterizing pediatric low and high grade gliomas has revolutionized treatment options for these patients, especially in pLGG. The implementation of next generation sequencing techniques for these tumors is crucial in obtaining less toxic and more efficacious treatments. What is Known: • Pediatric Gliomas are the most common brain tumour in children. They are responsible for significant morbidity and mortality in this population. What is New: • Over the last two decades, there has been a significant increase in our global understanding of the molecular background of pediatric low and high grade gliomas. • The implementation of next generation sequencing techniques for these tumors is crucial in obtaining less toxic and more efficacious treatments, with the ultimate goal of improving both the survival and the quality of life of these patients. [ABSTRACT FROM AUTHOR]

This study aimed to examine the feasibility of utilizing radiomics models derived from 18F-FDG PET/CT imaging to screen for T-cell lymphoma in children with lymphoma. All patients had undergone 18F-FDG PET/CT scans. Lesions were extracted from PET/CT and randomly divided into training and validation sets. Two different types of models were constructed as follows: features that are extracted from standardized uptake values (SUV)-associated parameters, and CT images were used to build SUV/CT-based model. Features that are derived from PET and CT images were used to build PET/CT-based model. Logistic regression (LR), linear support vector machine, support vector machine with the radial basis function kernel, neural networks, and adaptive boosting were performed as classifiers in each model. In the training sets, 77 patients, and 247 lesions were selected for building the models. In the validation sets, PET/CT-based model demonstrated better performance than that of SUV/CT-based model in the prediction of T-cell lymphoma. LR showed highest accuracy with 0.779 [0.697, 0.860], area under the receiver operating characteristic curve (AUC) with 0.863 [0.762, 0.963], and preferable goodness-of-fit in PET/CT-based model at the patient level. LR also showed best performance with accuracy of 0.838 [0.741, 0.936], AUC of 0.907 [0.839, 0.976], and preferable goodness-of-fit in PET/CT-based model at the lesion level. 18F-FDG PET/CT-based radiomics models with different machine learning classifiers were able to screen T-cell lymphoma in children with high accuracy, AUC, and preferable goodness-of-fit, providing incremental value compared with SUV-associated features. [ABSTRACT FROM AUTHOR]

The article focuses on discussing the most appropriate surgical approach for children with Wilms tumor, considering the risk of kidney disease and related considerations. Topics discussed include the rationale for nephron-sparing surgery, the impact of genetic predisposition on treatment decisions, and the importance of long-term kidney health monitoring in Wilms tumor survivors.

Purpose: Brain stem tumors in children < 3 months at diagnosis are extremely rare. Our aim is to study a retrospective cohort to improve the understanding of the disease course and guide patient management. Methods: This is a multicenter retrospective analysis across the European Society for Pediatric Oncology SIOP-E HGG/DIPG Working Group linked centers, including patients with a brainstem tumor diagnosed between 2009 and 2020 and aged < 3 months at diagnosis. Clinical data were collected, and imaging characteristics were analyzed blindly and independently by two neuroradiologists. Results: Five cases were identified. No patient received any therapy. The epicenter of two tumors was in the medulla oblongata alone and in the medulla oblongata and the pons in three. For patients with tumor in equal parts in the medulla oblongata and the pons (n = 3), the extension at diagnosis involved the spinal cord; for the two patients with the tumor epicenter in the medulla oblongata alone (n = 2), the extension at diagnosis included the pons (n = 2) and the spinal cord (n = 1). Biopsy was performed in one patient identifying a pilocytic astrocytoma. Two patients died. In one patient, autopsy revealed a high-grade glioma (case 3). Three survivors showed either spontaneous tumor regression (n = 2) or stable disease (n = 1). Survivors were followed up for 10, 7, and 0.6 years, respectively. One case had the typical imaging characteristics of a dorsal exophytic low-grade glioma. Conclusions: No patient fulfilled the radiologic criteria defining a high-grade glioma. Central neuroradiological review and biopsy may provide useful information regarding the patient management. [ABSTRACT FROM AUTHOR]

Medulloblastoma, the most common malignant brain tumor in children, presents a complex treatment challenge due to its propensity for infiltrative growth within the posterior fossa and its potential attachment to critical anatomical structures. Central to the management of medulloblastoma is the surgical resection of the tumor, which is a key determinant of patient prognosis. However, the extent of surgical resection (EOR), ranging from gross total resection (GTR) to subtotal resection (STR) or even biopsy, has been the subject of extensive debate and investigation within the medical community. Today, the impact of neurosurgical EOR on the prognosis of medulloblastoma patients remains a complex and evolving area of investigation. The conflicting findings in the literature, the challenges posed by critical surrounding anatomical structures, the potential for surgical complications and neurologic morbidity, and the nuanced interactions with molecular subgroups all contribute to the complexity of this issue. As the field continues to advance, the imperative to strike a delicate balance between maximizing resection and preserving quality of life remains central to the management of medulloblastoma patients. [ABSTRACT FROM AUTHOR]

Background: Extradural malignant rhabdoid tumors of the spine are highly malignant and invasive tumors (WHO grade IV) with poor prognosis, most frequently occurring in young children before 2 years of age. Pain and motor deficit are the most common presenting signs. Case description: We report a case of a 2-year-old girl presenting with axial ataxia and paraparesis related to an extradural malignant rhabdoid tumor causing posterior thoracic spinal cord compression (D3–D6). She underwent two near-total removal of the tumor, adjuvant chemotherapy according to the Eu-Rhab protocol and proton beam therapy. She then developed multiple cranial nerve paresis (meningeal carcinomatosis) after 4 cycles of chemotherapy and died at 4.32 months of follow-up. Discussion and conclusion: The role of the PET scan was essential to guide us to remove a residue, while two concomitant spinal MRIs were considered negative. We reviewed the 16 cases reported in the literature. Multiple surgeries and radiotherapy seem to be correlated with longer survival. No child younger than 2 years old had a documented survival higher than 4.32 months. [ABSTRACT FROM AUTHOR]

Osteosarcoma, a common malignant tumor in children, has emerged as a major threat to the life and health of pediatric patients. Presently, there are certain limitations in the diagnosis and treatment methods for this disease, resulting in inferior therapeutic outcomes. Therefore, it is of great importance to study its pathogenesis and explore innovative approaches to diagnosis and treatment. In this study, a non-negative matrix decomposition method was employed to conduct a comprehensive investigation and analysis of aggregated autophagy-related genes within 331,394 single-cell samples of osteosarcoma. Through this study, we have elucidated the intricate communication patterns among various cells within the tumor microenvironment. Based on the classification of aggregated autophagy-related genes, we are not only able to more accurately predict patients' prognosis but also offer robust guidance for treatment strategies. The findings of this study hold promise for breakthroughs in the diagnosis and treatment of osteosarcoma, intervention of aggrephagy is expected to improve the survival rate and quality of life of osteosarcoma patients. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor of the journal "Child's Nervous System" discussing patient positioning during surgery for fourth ventricular tumors in children. The author reflects on an article that argues for a telovelar approach without removing the posterior arch of C1, emphasizing the importance of the modified prone position. The author suggests that the surgeon's position is crucial, advocating for a lateral-posterior position. They also discuss the advantages and disadvantages of different patient positions, such as the sitting position and the prone position. The author concludes by supporting the removal of the posterior arch of C1 and emphasizing the importance of achieving a comfortable viewing angle for successful surgery. [Extracted from the article]

Background: Inflammatory myofibroblastic tumor is a rare yet profoundly impactful condition, particularly within the pediatric population. This case report illuminates the intricate challenges of diagnosing and managing inflammatory myofibroblastic tumors in children, underscoring the importance of interdisciplinary collaboration in formulating effective treatment strategies. Notably, the choice of surgical approach holds a paramount influence on the risk of recurrence and metastasis, with wide resection with bronchotomy, lobectomy, and pneumonectomy demonstrating significantly diminished recurrence rates compared to wedge resection in bronchoscopic removal. Case presentation: We present the case of a 3-year-old girl with a progressive, nonproductive cough, occasionally accompanied by episodes of hemoptysis and pneumonia for a year, secondary to an inflammatory myofibroblastic tumor that was removed by bronchotomy with excellent results. Conclusion: Given the extraordinary rarity of this disease in pediatric patients, ongoing research endeavors and the accumulation of collective expertise are paramount. [ABSTRACT FROM AUTHOR]

Background: Cisplatin is a chemotherapeutic drug commonly used in the treatment of many childhood solid malignancies. It is known to cause long-term nephrotoxicity, most commonly manifesting as reduced glomerular filtration rate and hypomagnesaemia. Existing literature regarding the epidemiology of long-term nephrotoxicity in childhood cancer describes large variation in prevalence and risk factors. Objectives: This study is to evaluate the prevalence of, and risk factors for, long-term cisplatin nephrotoxicity after treatment for childhood cancer. Study eligibility criteria: Studies were eligible for inclusion if they: (i) evaluated participants treated with cisplatin who were diagnosed with cancer < 18 years of age; (ii) investigated any author-defined measure of nephrotoxicity; and (iii) performed this evaluation 3 or more months after cisplatin cessation. Studies whose scope was broader than this were included if appropriate subgroup analysis was performed. Results: Prevalence of reduced glomerular filtration rate (GFR) ranged between 5.9 and 48.1%. Pooled prevalence of reduced GFR using studies with a modern consensus threshold of 90 ml/min/1.73 m2 was 29% (95% CI 0.0–58%). Prevalence of hypomagnesaemia ranged between 8.0 and 71.4%. Pooled prevalence of hypomagnesaemia was 37% (95% CI 22–51%). Substantial heterogeneity was present, with I2 statistics of 94% and 73% for reduced GFR and hypomagnesaemia respectively. All large, long-term follow-up studies described increased risk of reduced GFR with increasing cumulative cisplatin dose. Included studies varied as to whether cisplatin was a risk factor for proteinuria, and whether age was a risk factor for cisplatin nephrotoxicity. Limitations: A wide range of study methodologies were noted which impeded analysis. No studies yielded data from developing health-care settings. No non-English studies were included, further limiting generalisability. Conclusions: Both of the most common manifestations of long-term cisplatin nephrotoxicity have a prevalence of approximately a third, with increasing cumulative dose conferring increased risk of nephrotoxicity. Further work is needed to characterise the relationship between reduced GFR and hypomagnesaemia, investigate other risk factors and understand the interindividual variation in susceptibility to nephrotoxicity. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a rare primary brain tumor in children, and extracranial metastases of pediatric GBM are particularly uncommon. We present the case of a 10-year-old girl with pediatric GBM who developed multiple extracranial metastases, including cervical lymph nodes, spine, and lung. We discuss the rarity of extracranial metastases in GBM and explore possible mechanisms of dissemination. The patient underwent surgical resections, radiotherapy, and chemotherapy, but the metastatic disease progressed despite treatment. We emphasize the need to consider extracranial metastases in pediatric GBM patients and adopt multimodal treatment approaches for managing this rare clinical entity. As the survival rates of pediatric GBM patients are improving, awareness of extracranial metastases is crucial for optimizing treatment outcomes. [ABSTRACT FROM AUTHOR]

Parents of children with cancer face a high level of distress. One contributing factor to this is their need to make life-altering treatment decisions. To understand specific variables that may contribute to parents' distress and decision-making preferences, we assessed correlations between parent anxiety, decision-making preferences, personal variables (gender, age, education, socioeconomic, occupational status), cancer characteristics (type, stage, time since diagnosis), existing support system, and trust in the medical staff. Sixty-nine parents of children with cancer during the first year after diagnosis were recruited to the study during hospitalization in a large medical center. Anxiety was measured by the State-Trait Anxiety inventory, decision-making preferences were assessed by the Control Preferences Scales for Pediatrics, support system and trust were measured by questionnaires developed for the present study. Parents' anxiety level was significantly higher than the general population, especially for state anxiety. Higher socioeconomic status and greater extent of employment of the spouse related to higher levels of state anxiety. Anxiety did not relate to any of the cancer properties, nor to the amount of support the parents had or their trust in the medical staff. Parents' level of education positively related with willingness to take part in decision-making, as well as with trust in the medical staff. The results emphasize the importance of trust in and the support of the medical and psychosocial staff and the need to be attuned to different parents' needs to increase this trust. Highlights: This study examines personal and environmental variables impacting parental anxiety and decision-making. Parents displayed notably elevated anxiety levels, particularly in terms of state anxiety, compared to the general population. High socioeconomic status and greater spousal employment correlated with heightened state anxiety. Parents' educational attainment positively influenced their willingness to participate in decision-making and trust in medical professionals. Results emphasize the importance of trust in and support of medical and psychosocial staff and being attuned to different parents' needs to increase this trust. [ABSTRACT FROM AUTHOR]

This paper aims to explore the epidemiology, clinical characteristics, and prognosis of extracranial malignant rhabdoid tumors (eMRTs) in children. A systematic review and meta-analysis of studies published in PUBMED, MEDLINE, Web of Science, Embase, Cochrane, and China National Knowledge Infrastructure (CNKI) was conducted. The search was limited to studies published between Jan 1, 1990 to Dec 31, 2022, with the last search done on Jan 31, 2023. We identified 496 papers through the literature search, and 12 retrospective cohort studies with 398 patients were included. The pooled age at diagnosis for malignant rhabdoid tumor of the kidney (MRTK) was 10.009 months (95%CI (7.542–12.476)), while extracranial malignant rhabdoid tumor (EERT) was 25.917 months (95%CI (17.304–34.530)). Among the 398 patients with eMRTs, chemotherapy treatment rate (86.8% (95%CI (74.4–96.0%))) was more frequently than radiotherapy treatment (45.4% (95%CI (38.1–52.6%))). The rate of metastasis in all patients was 41.4% (95%CI (33.9–48.9%)), in which the lung metastasis was occupied 70.4% (95%CI (58.0–81.6%)). SMARCB1/INI1 mutation was up to 93.2% (95%CI (81.3–99.8%)). The rate of total surgical resection was 50.4% (95%CI (35.2–65.6%)), while pooled proportion of death in all patients was 68.7% (95%CI (56.9–79.5%)). Conclusion: EMRTs are highly malignant tumors associated with high mortality rates. The loss of SMARCB1/INI1 gene and the protein expression is observed in the vast majority of eMRTs patients. Patients that suffered MRTK are younger than patients with extrarenal EERT and are more prone to lung metastasis, but there is no significant difference in overall survival, possibly due to the higher rate of R0 resection of primary tumors in MRTK. Trial registration: The study was registered on PROSPERO with registration number CRD42023400985. What is Known: • Malignant rhabdoid tumor (MRT) is a rare and highly malignant tumor that may originate from embryonic stem cells. The incidence of MRT is exceptionally low, estimated at 0.00006%. • Malignant rhabdoid tumor of the kidney (MRTK) and extrarenal extra-cranial malignant rhabdoid tumor (EERT) tend to manifest between 11 to 18 months of age, with a 5-year survival rate of approximately 17%-36%. What is New: • There is no comprehensive meta-analysis or large-scale case series that reported to systematically introduce the eMRTs clinic outcome and prog-nosis based on largely pooled data. • This study performed a meta-analysis through an extensive literature search and clinical data analysis in order to mainly explore the clinical characteris-tics and prognosis of eMRTs, improving the understanding of eMRTs in children.. [ABSTRACT FROM AUTHOR]

Introduction: Craniopharyngioma constitutes approximately 10% of primary brain tumors in children. It can cause considerable morbidity and mortality due to the local aggressiveness of the tumor itself or its management affecting the hypothalamus-pituitary axis and optic pathway involvement. There is very scarce data available from LMIC which makes the management controversial where multidisciplinary teams are already not available in most of the centers. This is a single-center cross-sectional retrospective review of 20-year record of 49 patients with craniopharyngioma treated between 2001 and 2020 at Aga Khan University Hospital, a tertiary care center in Karachi, Pakistan. Methods: We have assessed the epidemiological data of children presenting with the diagnosis of craniopharyngioma, treatment modalities used, and neurological, endocrine, and hypothalamic complications in these patients. The assessment involved a retrospective review of medical records and medical follow-up. Results: Out of a total of 49 patients, 26 (53%) were male, and 23 (46.9%) were female. The mean age was 9.5 years (SD ± 4.5 years). Most common symptoms at initial presentation were headache 41 (83.6%), visual deficit 40 (81.6%), nausea and vomiting 26 (53%), and endocrine abnormalities 16 (32%). Treatment modalities used at our center include gross total resection 11 (22%) and subtotal resection 38 (77%) out of total, while 6 (12.2%) patients received intracystic interferon. Histopathologic findings of the majority of patients (40 (81%)) revealed an adamantinomatous type of tumor. Only 23 (46.9%) children followed in clinic post-op. Median follow-up after craniopharyngioma presentation was 5 years (± 2.1 SD, range: 2–10 years). Pituitary hormone deficiencies (98%) and visual disturbances (75%) were the most common long-term health conditions observed. Conclusions: Since pituitary hormone deficiencies and visual disturbance were the most common long-term health conditions observed in our study, these patients require a multidisciplinary team follow-up to improve their quality of life. [ABSTRACT FROM AUTHOR]

Wilms tumor (WT) represents over 90% of all pediatric kidney tumors. Children with WT often present acutely with hypertension which resolves in the short term after nephrectomy. However, WT survivors have increased long-term risk of hypertension, primarily due to decreased nephron mass after nephrectomy, with additional insults from possible exposure to abdominal radiation and nephrotoxic therapies. The diagnosis of hypertension may be improved by ambulatory blood pressure monitoring (ABPM), as several recent single-center studies have shown a substantial proportion of WT survivors with masked hypertension. Current gaps in knowledge include determining which WT patients may benefit from routine screening with ABPM, correlation of casual and ABPM parameters with cardiac abnormalities, and longitudinal assessment of cardiovascular and kidney parameters in relation to appropriate treatment of hypertension. This review aims to summarize the most recent literature on hypertension presentation and management at the time of WT diagnosis as well as the long-term hypertension risk and impact on kidney and cardiovascular outcomes in WT survivors. [ABSTRACT FROM AUTHOR]

Introduction: The Cirq robotic alignment system (Brainlab, Munich, Germany) is a manually adjustable electronic arm with a robotic alignment module on its distal end, enabling the neurosurgeon to automatically and accurately align surgical instruments to a preoperatively planned trajectory. In this study, we share our first experiences and results using Cirq for intracranial tumor biopsy in children. Methods: From May 2021 until October 2022, all consecutive patients that underwent a brain tumor biopsy using Cirq were included and compared to a historical cohort of patients biopsied with the non-robotic system Varioguide (Brainlab, Munich, Germany). Patient-related data, tumor-related data, and surgery-related data were collected. Registration accuracy was calculated for different patient-to-image registration methods. Pre- and postoperative images were fused, and entry error, target error, and angulation error were calculated. Results: Thirty-seven patients, aged 1–19 years, were included (14 with Cirq and 23 with Varioguide). An integrated histopathological and molecular diagnosis was acquired in all cases. Patient-to-image registration was significantly more accurate when based on bone screw fiducials combined with intraoperative CT, as compared to surface matching or skin fiducials. The target error (Euclidian distance) was 5.3 mm for Cirq as compared to 8.3 mm for Varioguide, but this was not statistically significant. Entry error and angulation error were also not significantly different between both groups. Conclusion: Intracranial biopsy with the Cirq robotic system is feasible and safe, and its accuracy does not differ from the Varioguide system. [ABSTRACT FROM AUTHOR]

Background: Weight loss and malnutrition are common findings in pediatric oncology patients, but their prognostic significance is controversial. We sought to evaluate the correlation between weight loss and response to neo-adjuvant chemotherapy in pediatric patients with osteosarcoma. Procedure: All medical files of patients treated for osteosarcoma in a single pediatric haemato-oncology center between January 2011 and October 2022 were retrospectively reviewed. Results: Sixty-three patients were suitable for study inclusion. Data on changes in their body weight between the initiation of neo-adjuvant chemotherapy and local therapy (tumor resection) were extracted. Response to chemotherapy was assessed by the percentage of tumor necrosis at the time of surgery. There was a significant direct correlation between a weight loss of 3% and above and good response to chemotherapy as demonstrated by tumor necrosis above 90%. Conclusions: Low caloric intake may imitate a caloric restriction diet that was proven to improve response to therapy in some oncological diseases. Further prospective trials are needed for the establishment of recommended caloric intake during chemotherapy in pediatric patients with osteosarcoma. [ABSTRACT FROM AUTHOR]

Purpose: Robotic surgery is becoming increasingly widely used in the field of pediatric surgery. The present study aimed to evaluate the safety and feasibility of robot-assisted resection of benign pediatric splenic tumors and to discuss the technical points. Methods: A total of 32 patients who were diagnosed with benign splenic tumors and underwent minimally invasive surgery from January 2017 to September 2023 were included in the study. The clinical data including demographic criteria, operative details, and postoperative outcomes were analyzed retrospectively. Results: Thirteen patients underwent robot-assisted surgery, and 19 patients underwent laparoscopic surgery. The median operation time was 150 min, with an interquartile range (IQR) of 120 to 200 min for the robot-assisted group and 140 min with an IQR of 105 to 180 min in the laparoscopic group (P = 0.318). Despite four cases in the laparoscopic group (21%) being converted to laparotomy because of intraoperative bleeding, compared with none in the robot-assisted group, there was no significant difference between two groups (P = 0.128). The intraoperative volume of blood loss was significantly less (P = 0.041), and the hospitalization expense was significantly higher (P = 0.000) in the robot-assisted group than for the laparoscopic group. There was no significant difference in patients' age, tumor size, postoperative feeding time, and the postoperative hospitalization time between two groups (P > 0.05). Conclusion: Robot-assisted benign splenic tumor resection was safe and feasible, and it reduced surgical trauma for the pediatric patient. [ABSTRACT FROM AUTHOR]

While in adults most intracranial tumors develop around the cerebral hemispheres, 45 to 60% of pediatric lesions are found in the posterior fossa, although this anatomical region represents only 10% of the intracranial volume. The latest edition of the WHO classification for CNS tumors presented some fundamental paradigm shifts that particularly affected the classification of pediatric tumors, also influencing those that affect posterior fossa. Molecular biomarkers play an important role in the diagnosis, prognosis, and treatment of childhood posterior fossa tumors and can be used to predict patient outcomes and response to treatment and monitor its effectiveness. Although genetic studies have identified several posterior fossa tumor types, differing in terms of their location, cell of origin, genetic mechanisms, and clinical behavior, recent management strategies still depend on uniform approaches, mainly based on the extent of resection. However, significant progress has been made in guiding therapy decisions with biological or molecular stratification criteria and utilizing molecularly targeted treatments that address specific tumor biological characteristics. The primary focus of this review is on the latest advances in the diagnosis and treatment of common subtypes of posterior fossa tumors in children, as well as potential therapeutic approaches in the future. Conclusion: Molecular biomarkers play a central role, not only in the diagnosis and prognosis of posterior fossa tumors in children but also in customizing treatment plans. They anticipate patient outcomes, measure treatment responses, and assess therapeutic effectiveness. Advances in neuroimaging and treatment have significantly enhanced outcomes for children with these tumors. What is Known: • Central nervous system tumors are the most common solid neoplasms in children and adolescents, with approximately 45 to 60% of them located in the posterior fossa. • Multimodal approaches that include neurosurgery, radiation therapy, and chemotherapy are typically used to manage childhood posterior fossa tumors What is New: • Notable progress has been achieved in the diagnosis, categorization and management of posterior fossa tumors in children, leading to improvement in survival and quality of life. [ABSTRACT FROM AUTHOR]

Trials. The study aimed to investigate the effect of virtual reality interventions on relieving pain and anxiety in children and adolescents receiving cancer treatment. A search that involved Cochrane Library (comprising Cochrane Central Register of Controlled Trials (CENTRAL)), PubMed, ProQuest, MEDLINE, Web of Sciences, Science Direct, and Scopus electronic databases covering the records from January 1, 2000 up to May, 2023 was conducted to determine randomized controlled trials that could be included in our study. The results of the search were limited to "anxiety and pain, adolescents, children, virtual reality, cancer." Of the 160 articles that were reached during the search, seven were found eligible based on inclusion criteria. Hedges' g effect size was calculated for each article. Random effects model was used to test effect sizes and moderator variables. The registration number of this meta-analysis on PROSPERO is CRD42022304737. The outcomes were pain and anxiety. Compared with standard care, virtual reality had a medium and significant effect on anxiety (g = 0.60, 95% CI: [− 1.05 − 0.15]) and pain (g = − 0.667, 95% CI: [− 1.08− -0.24]). In addition, age has been identified as an important moderator in the use of virtual reality in pain management. This meta-analysis shows that virtual reality applications are effective interventions for reducing pain and anxiety in the field of pediatric oncology. However, it is necessary to carry out randomized controlled trials that have large samples for evidence-based virtual reality applications in pediatric oncology. [ABSTRACT FROM AUTHOR]

During the last 30 years, the neurosurgeons have witnessed a revolution in the practice of interventricular surgery. The advent of neuroendoscopy at the end of the 1980s has allowed a minimally invasive management of a very large series of pathologies in pediatric neurosurgery ranging from hydrocephalus to arachnoid cyst to intraventricular tumors. The progresses in the management of hydrocephalus, intracranial cyst, and the fluid filled collection nevertheless has been more rapid and radical due to the simpler equipment that is necessary to perform this kind of surgery. The intraventricular tumors instead have been addressed in a slower way, and for many years, the only endoscopic procedure that was allowed on interventricular tumors was a biopsy associated with the management of hydrocephalus. Only very small tumors have been considered operable for complete removal during many years due to the limitations of the neuroendoscopic equipment and to the small calibers of the working channel. More recently, the advent of new devices and new surgical techniques are offering new perspectives on the possibility of intraventricular tumor surgery in children. In this review, we describe the historical perspective of the learning curve of intraventricular tumor surgery under neuroendoscopic control and try to offer a view of the future perspective in the removal of larger intraventricular tumors, analyzing the main indications for intraventricular endoscopic tumor surgery. We offer as well an historical perspective of the evolution of skull base surgery and endonasal transsphenoidal approach for skull-based tumors in children. This kind of surgery that has acquired widespread acceptance for many pathologies in adult age has diffused more slowly in pediatric neurosurgery due to the anatomical limitation observed in these age range. Also in this field, the slow evolution of the technique and of the technology available to neurosurgeons has allowed a very significant expansion of indication for the minimally invasive removal of skull base tumors in children. [ABSTRACT FROM AUTHOR]

Introduction: Pineal region tumors (PRTs) are tumors arising from the pineal gland and the paraspinal structures. These tumors are rare and heterogeneous that account for 2.8–10.1% and 0.6–3.2% of tumors in children and in all ages, respectively. Almost all types and subtypes of CNS tumors may be diagnosed in this region. These tumors come from cells of the pineal gland (pinealocytes and neuroglial cells), ectopic primordial germ cells (PGC), and cells from adjacent structures. Hence, PRTs are consisted of pineal parenchyma tumors (PPTs), germ cell tumors (GCTs), neuroepithelial tumors (NETs), other miscellaneous types of tumors, cystic tumors (epidermoid, dermoid), and pineal cyst in addition. The symptoms of PRTs correlate to the increased intracranial cranial pressure due to obstructive hydrocephalus and dorsal midbrain compression. The diagnostic imaging studies are mainly MRI of brain (with and without gadolinium) along with a sagittal view of whole spine. Serum and/or CSF AFP/β-HCG helps to identify GCTs. The treatment of PRTs is consisted of the selection of surgical biopsy/resection, handling of hydrocephalus, neoadjuvant and/or adjuvant therapy according to age, tumor location, histopathological/molecular classification, grading of tumors, staging, and threshold value of markers (for GCTs) in addition. Methods: In this article, we review the following focus points: 1. Background of pineal region tumors. 2. Pineal GCTs and evolution of management. 3. Molecular study for GCTs and pineal parenchymal tumors. 4. Review of surgical approaches to the pineal region. 5. Contribution of endoscopy. 6. Adjuvant therapy (chemotherapy, radiotherapy, and combination). 7. Future direction. Results: In all ages, the leading three types of PRTs in western countries were PPTs (22.7–34.8%), GCTs (27.3–34.4%), and NETs (17.2–28%). In children and young adults, the leading PRTs were invariably in the order of GCTs (40–80.5%), PPTs (7.6–21.6%), NETs (2.4–37.5%). Surgical biopsy/resection of PRTs is important for precision diagnosis and therapy. Safe resection with acceptable low mortality and morbidity was achieved after 1970s because of the advancement of surgical approaches, CSF shunt and valve system, microscopic and endoscopic surgery. Following histopathological diagnosis and classification of types and subtypes of PRTs, in PPTs, through molecular profiling, four molecular groups of pineoblastoma (PB) and their oncogenic driver were identified. Hence, molecular stratified precision therapy can be achieved. Conclusion: Modern endoscopic and microsurgical approaches help to achieve precise histopathological diagnosis and molecular classification of different types and subtypes of pineal region tumors for risk-stratified optimal, effective, and protective therapy. In the future, molecular analysis of biospecimen (CSF and blood) along with AI radiomics on tumor imaging integrating clinical and bioinformation may help for personalized and risk-stratified management of patients with pineal region tumors. [ABSTRACT FROM AUTHOR]

Objectives: Evaluate mandibular cortical bone in childhood cancer survivors (CCS) and correlate findings with disease and treatment characteristics. Methods: Dental panoramic radiographs of 60 CCS and of 120 age and gender-matched healthy individuals were assessed by two independent observers. Bone was categorized as normal, moderately or severely eroded and its width was calculated at four sites bilaterally. Significant differences were tested using Chi-square and Pearson correlation co-efficient. Possible risk factors were detected by multivariate regression analysis. Results: Forty five percent of CCS had moderately eroded bone, while 67% of healthy individuals normal bone. Mean width was 3.9 mm in CCS (1.9 mm–6.4 mm) and 2.7 mm in healthy controls (1.4 mm–6 mm). None of the above differences were significant. Survivors diagnosed at a younger age had a five times greater probability of presenting mildly eroded bone. Conclusions: No direct effect of antineoplastic treatment on cortical bone could be demonstrated in the current study, underlying the need for more well-designed studies. [ABSTRACT FROM AUTHOR]