Pediatric Tumors Research Articles

Unraveling the landscape of pediatric pancreatic tumors: Insights from Japan

Pediatric pancreatic tumors, though rare, pose significant diagnostic and management challenges. The recent, 22-year nationwide survey on pediatric pancreatic tumors in Japan by Makita et al offers valuable insights into this uncommon entity, revealing striking geographical variations and questioning current treatment paradigms. This editorial commentary analyzes the study's key findings, including the predominance of solid pseudopapillary neoplasms and their younger age of onset, which contrast sharply with Western data. It explores the implications for clinical practice and research, emphasizing the need for population-specific approaches to diagnosis and treatment. The revealed limited institutional experience and surgical management patterns prompt a reevaluation of optimal care delivery for these complex cases, suggesting benefits of centralizing healthcare services. Furthermore, the commentary advocates for international collaborative studies to elucidate the genetic, environmental, and lifestyle factors influencing the development and progression of pediatric pancreatic tumors across diverse populations. It also outlines future directions, calling for advancements in precision medicine and innovative care delivery models to improve global patient outcomes. Unraveling Makita et al 's findings within the broader landscape of pediatric oncology can stimulate further research and clinical advancements in managing pancreatic and other rare tumors in children.

Comparative analysis of treatment modalities for pediatric spinal cord glioblastoma: insights from a meta-analysis.

Glioblastomas (GBM) are aggressive tumors that make up about 7% of central nervous system tumors in children. Spinal GBMs (sGBMs) are extremely rare, accounting for less than 1% of pediatric spinal tumors. sGBMs are difficult to treat due to their infiltrative nature and cause significant morbidity. While there is extensive literature on treatment outcomes for cranial GBMs, there is limited research on pediatric sGBMs. This meta-analysis aims to assess the impact of available treatments on overall survival (OS) and progression-free survival (PFS) in pediatric sGBM patients and to identify prognostic factors. A comprehensive review of pediatric sGBM cases up to June 2024 was conducted using PubMed and Mendeley. Inclusion criteria were case series and case reports of pediatric sGBM, excluding those with metastatic sGBM or aggregated patient data. A total of 2202 articles were identified, with 46 meeting the inclusion criteria. Data on demographics, tumor characteristics, extent of resection, and treatments were collected. Kaplan-Meier and Cox proportional hazards models were used for statistical analysis. The data was collected from 81 patients, 43 females and 38 males, with an average age of 10.7years. The majority of tumors were found in the cervical region (32%). Subtotal resection (STR) was performed in 53% of cases, and 59% of patients received both chemotherapy (QT) and radiotherapy (RT). The average progression-free survival (PFS) was 10.95months, with RT significantly improving PFS (15.2months vs. 2.1months, p = 0.001). The average OS was 13.4months, with RT and QT being significant protective factors (p < 0.05). Age over seven years and cervical tumor location were associated with worse OS. This study highlights the significance of radiation therapy and chemotherapy in enhancing overall survival and progression-free survival in pediatric patients with spinal cord glioblastoma. Specifically, RT significantly improves PFS, while advanced age and tumor location in the cervical region are associated with worse outcomes. These findings can help shape treatment approaches and ultimately enhance the quality of life for pediatric sGBM patients.

Coexisting Congenital Mesoblastic Nephroma and Lissencephaly: Unique Case Report with Pathological Analysis and Its Clinical Significance

Background: Congenital mesoblastic nephroma represents 3–10% of all pediatric renal tumors. With the advancement of ultrasound diagnostics and magnetic resonance imaging, the diagnosis of this renal neoplasm is increasingly being established prenatally and at birth. It usually presents as a benign tumor, but it can severely affect pregnancy outcomes, contributing to perinatal morbidity and mortality. Lissencephaly belongs to a rare category of neurodevelopmental disorders marked by the absence of a substantial reduction in the typical folds and grooves in the cerebral cortex. The prognosis for patients with lissencephaly is extremely poor, carrying with it a high mortality rate. Case Presentation: We present a case of congenital mesoblastic nephroma (CMN) diagnosed with polyhydramnios at 28 weeks of gestation, which led to preterm delivery at 29 weeks and a fatal outcome for the newborn. Histopathological examination confirmed the diagnosis of CMN along with fetal pachygyria/lissencephaly. The aim of this study is to point out the characteristics and unique correlation between CMN and lissencephaly, and to illustrate the histopathological features of CMN and lissencephaly through an educational example derived from our presented index case. To the best to our knowledge, the association of CMN with lissencephaly has not been described in the literature so far. Conclusions: Outlining the prenatal progression of CMN and the outcome of pregnancies involving fetal CMN and lissencephaly, this case underscores the importance of comprehensive ultrasound examinations, including central nervous system evaluation, to identify potential coexisting anomalies and refine prenatal diagnostic practices.

Familial History in Ovarian Teratomas Is a Frequent Event: 22 Years' Experience at a Single Center.

Ovarian mature teratoma represents the most common benign neoplasm among pediatric germ cell tumors. This study reports the prevalence and characteristics of familial forms identified in a single center over 22 years in order to better understand possible familial predispositions to ovarian teratoma. The records of all patients who were surgically treated for ovarian teratoma between 2000 and 2022 were retrospectively reviewed. Families were systematically asked about a possible family history of ovarian tumors (benign or malignant) or testicular germ cell tumors. Among the 136 patients operated on for ovarian teratoma, 24 cases of familial form (18%) were identified. Patients with familial history of ovarian mature teratoma were more likely to have multifocal tumors at diagnosis and metachronous lesions over time (p = 0.032 and p = 0.018, respectively) compared with patients without familial history. The family history concerned first-degree relatives in 12/24 cases (50%) including one case of twin monozygotic sisters, and affected two consecutive generations in three cases. A systematic examination made it possible to find up to 18% of familial forms in mature teratomas of the ovary, which in these cases seem to be more likely multifocal. The underlying genetic mechanisms are likely to be heterogeneous. Further work seems to be necessary to provide a better understanding of the genesis of germ cell tumors.

Rhabdomyosarcoma Surgical Update.

Rhabdomyosarcoma (RMS) tumors arise from mesenchymal tissue and represent half of pediatric sarcomas, which in turn make up 7% of pediatric tumors. Advances in local control therapy of RMS have improved outcomes after surgical resection of the primary tumor, either before or after induction chemotherapy, even in the setting of metastatic disease. The utilization of diagnostic core needle and sentinel node biopsy techniques for lymph node staging are becoming more widely used. Over the past several years, refinement of prognostic factors with adoption of fusion status instead of histology, and optimized risk stratification schemas have been developed to assure appropriate therapy. There have been efforts between North American and European surgical oncology cooperative groups to standardize the care we provide, and yet there are still some philosophical differences to overcome.

Pediatric Borderline Ovarian Tumors: A Retrospective Study of 15 Cases at a Single Institution.

Borderline ovarian tumors (BOTs) are rare in pediatric populations and typically follow an indolent clinical course with few reported recurrences. Consequently, guidelines for pediatric BOT management are minimal. We retrospectively examined the management of 15 adolescent patients who underwent BOT resection at our institution over 14 years, with a specific focus on recurrence. Data collected include age, symptoms, tumor characteristics, laboratory markers, surgical management, staging, and follow-up. Fifteen patients with BOTs (median age: 16y) presented with abdominal pain (67%), or distention (33%). Cancer antigen-125 marker was elevated in 10/13 patients. There were 11 (73%) tumors with serous and 4 (23%) with mucinous histology. Most received fertility-preserving surgery (93%) and disease stage was 1A in 7 (47%), 1B/1C in 5 (33%), and stage 2B or higher in 3 (20%) patients. Additional staging procedures, including peritoneal washings (73%), omentectomy (53%), and peritoneal biopsy (47%), varied in use. Four (27%) patients recurred, with 1 case of benign tumor, 1 BOT, and 2 serous carcinomas. Median patient follow-up was 45 months. BOTs can be successfully treated with fertility-preserving surgery but demonstrate a non-negligible rate of recurrence. We recommend surgical staging and posttreatment surveillance for all patients with BOT.

Updates on Langerhans cell histiocytosis and other histiocytosis in children: invited review-challenges and novelties in paediatric tumours.

Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG) family lesions, and Rosai-Dorfman-Destombes disease (RDD) are now classified by the World Health Organization (WHO) under the heading of histiocytic/dendritic cell neoplasms. Each disease may manifest as a focal lesion, as multiple lesions, or as a widespread aggressive systemic disease with visceral organ involvement. Erdheim-Chester disease (ECD) is a rare systemic disease process of adults with limited cases in children. Challenges in diagnosis and novel disease presentations, including ALK-positive histiocytosis (a newly recognized WHO entity), mixed histiocytosis, and secondary histiocytic lesions following a prior leukemia/lymphoma are also discussed. Malignant histiocytic neoplasms (MHN) are distinct high-grade histiocytosis, which while rare in childhood occur both as primary disease and as secondarily after a prior hematologic malignancy. Of note, despite its name, hemophagocytic lymphohistiocytosis (HLH) is not considered a histiocytic neoplasm and does not define one specific disease "entity." HLH is a spectrum of hyperinflammation with various triggers and is not covered for the purposes of this targeted review.

Long-term epidemiological trends in (primary) pediatric central nervous system tumors: a 25-year cohort analysis in Western Mexico.

Central nervous system tumors (CNSTs) represent a significant oncological challenge in pediatric populations, particularly in developing regions where access to diagnostic and therapeutic resources is limited. This research investigates the epidemiology, histological classifications, and survival outcomes of CNST in a cohort of pediatric patients aged 0 to 19years within a 25-year retrospective study at the Civil Hospital of Guadalajara, Mexico, from 1999 to 2024. Data was analyzed from 273 patients who met inclusion criteria, revealing a higher incidence in males (51.6%) with a mean age at diagnosis of 8.2years. Histological analysis revealed gliomas as the most common type (52.7%), followed by embryonal tumors (28.6%). High-grade tumors (WHO grade 4) comprised 49.8% of cases, demonstrating significantly poorer survival outcomes (median overall survival of 13.5months) compared to lower-grade tumors (up to 57months). The predominance of tumors in the supratentorial region and the notable differences in survival outcomes by tumor type underscore the varied impact of geographical and socioeconomic factors on pediatric oncology in Mexico. This study highlights the critical need for improved healthcare infrastructure and early diagnosis initiatives, as well as the importance of targeted research to address disparities in treatment and outcomes for pediatric CNST in this region.

Establishing a living biobank of pediatric high-grade glioma and ependymoma suitable for cancer pharmacology.

Brain tumors are the deadliest solid tumors in children and adolescents. Most of these tumors are glial in origin and exhibit strong heterogeneity, hampering the development of effective therapeutic strategies. In the past decades, patient-derived tumor organoids (PDT-O) have emerged as powerful tools for modeling tumoral cell diversity and dynamics, and they could then help defining new therapeutic options for pediatric brain tumors. Through an integrative approach based on our expertise and a careful review of the literature about glioblastoma 3D primary cultures, we set-up a standardized methodological pipeline for the establishment, characterization and biobanking of PDT-O through direct 3D in vitro culture of the deadliest pediatric glial brain tumors. To assess PDT-O fidelity and validate their pre-clinical relevance, we performed comprehensive histological, molecular and drug-response analyses. Our methodological pipeline allowed the rapid and efficient generation of PDT-O recapitulating their parental tumor features, including intra-tumoral heterogeneity, even after several passages and cryopreservation/revival as 3D cultures. Moreover, we successfully performed pre-clinical test responses on these PDT-O to standard-of-care therapies and new therapeutic options. Finally, we identified ONC201 as a selective drug for pediatric glial tumor types not restricted to H3K27M-mutant glioma, as well as combination strategies to increase the therapeutic response to ONC201. Hence, we describe a fast and robust process to biobank PDT-O for pediatric glial brain tumors. These PDT-O models have the potential for patient-specific modeling even after long-term expansion in vitro and we established the proof-of-concept of their usefulness to support powerful pre-clinical studies.

Paediatric renal tumours: an update on challenges and recent developments.

Paediatric renal tumours include a broad range of neoplasms which largely differ, but also overlap to a smaller extent, with adult kidney cancer. These include the embryonal tumour nephroblastoma, which accounts for the majority of cases of kidney cancer in the first decade of life and, despite boasting a cure in ~ 90% cases, still presents clinical challenges in a small proportion of cases. A variety of less common mesenchymal tumours, including the mostly indolent congenital mesoblastic nephroma, clear cell sarcoma of kidney which continues to be associated with poor outcomes for higher stage disease, and the typically lethal malignant rhabdoid tumour, form the bulk of the remaining presentations in the first decade. All three of these represent the intrarenal form of a wider 'family' of genetically related and histologically overlapping entities occurring in soft tissue and other anatomical locations. The latter two are examples of aggressive 'epigenetic' tumours driven by dysregulation of chromatin. In the second decade of life, renal cell carcinoma dominates, and with molecular characterisation many distinct subtypes are now described. Herein we discuss the developments in relation to diagnostic categorisation of paediatric renal cancers and how deeper understanding of the underlying biology is already providing therapeutic opportunity, while also focussing on the challenges that remain for the pathologist.

Germ cell tumors in children.

Pediatric germ cell tumors represent a rare but biologically diverse group of neoplasms arising from pluripotent primordial germ cells. The 2022 edition of the WHO Classification of Pediatric Tumors introduced the first organ independent classification of germ cell tumors, reflecting advances in molecular biology, histopathology, and clinical practice. This review highlights the key changes, including the refined distinctions between the different subtypes. These updates enhance diagnostic accuracy and provide a framework for understanding age-dependent differences in tumor biology and behavior. Emphasis is placed on integrating the new classification into multidisciplinary care, particularly in addressing diagnostic challenges in pre- and post-pubertal-type germ cell tumors. By bridging the gap between histopathology and oncology, the updated classification represents a pivotal step forward in improving outcomes for children with germ cell tumors.

Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG. The primary objectives were to assess feasibility and tolerability, which were both met. Secondary objectives included assessments of CAR T cell distribution and survival. A total of 23 patients with DIPG enrolled, and 21 were treated with repeated doses of ICV B7-H3 CAR T cells using intra-patient dose-escalation regimens without previous lymphodepletion. Concurrent tumor-directed therapy, including re-irradiation, was not allowed while on protocol therapy. We delivered a total of 253 ICV doses and established the highest planned dose regimen, DR4, which escalated up to 10 × 107 cells per dose, as the maximally tolerated dose regimen. Common adverse events included headache, fatigue and fever. There was one dose-limiting toxicity (intratumoral hemorrhage) during DR2. For all treated patients (n = 21), the median survival from their initial CAR T cell infusion was 10.7 months and the median survival from diagnosis was 19.8 months with 3 patients still alive at 44, 45 and 52 months from diagnosis. Ultimately, this completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable, including multiyear repeated dosing, and may have clinical efficacy that warrants further investigation on a multisite phase 2 trial. ClinicalTrials.gov registration: NCT04185038 .

A Rare Pediatric Giant Cell Tumor of the Clivus Bone, H3.3 p.Gly35Trp-mutated: Case Report and Mini-review of the Literature.

Introduction: Giant cell tumor of bone (GCTB) is a rare, typically benign neoplasm that primarily affects long bones in adults, with clival involvement being extremely rare, particularly in pediatric cases: a mini-review shows a total of 28 described cases, of which only 5 were truly pediatric (within 14 years of age). Surgery is the treatment of choice, and Denosumab is reported to be the most effective drug therapy. To date, the GCTB's molecular hallmark is the somatic mutation p.Gly34Trp, at the H3F3A gene (H3.3 p.Gly34Trp mutation), but in this case, the mutation H3.3 p.Gly35Trp was identified. Case Presentation: A 9-year-old female presented with progressive ocular pain, ptosis, and diplopia. MRI revealed a 42 × 32 × 30 mm mass in the clivus and sphenoid body. The patient underwent partial resection, and histology confirmed GCTB. Molecular testing revealed the presence of the H3.3 p.Gly35Trp mutation, and we demonstrate that this is the true mutation associated with GCTB, not the previously described (H3.3 p.Gly34Trp). Due to residual tumor tissue, the patient was treated with Denosumab, a RANKL inhibitor. During a 2-year follow-up, the tumor size stabilized, and no significant adverse effects were observed. Conclusion: This case represents the first pediatric clival GCTB harboring the H3.3 p.Gly35Trp mutation. Molecular diagnostics played a crucial role in confirming the diagnosis and demonstrating that the true mutation harbored by GCTB is H3.3 p.Gly35Trp and not the formerly described (H3.3 p.Gly34Trp). Denosumab therapy effectively controlled the tumor without major side effects, although long-term treatment duration and safety require further study.

Prognostic Correlation of Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor with Radiological Tumor Size in Pediatric Nephroblastoma and Neuroblastoma: A Prospective Study

ABSTRACT Introduction: Angiogenesis plays an important role in the growth, progression, and metastasis of solid tumors. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF); both are potent angiogenic factors implicated with the growth and metastasis of solid tumors mostly in adult studies. Rapidly growing and large-size tumors have a positive correlation with these factors which are measured in serum and urine samples of patients. There is little literature available for pediatric patients that compare the computed tomography findings (size) of pediatric solid tumors with serum VEGF and serum/urinary bFGF. This prospective study aims to determine the correlation of serum VEGF and serum/urinary bFGF with the size of common pediatric solid tumors (nephroblastoma and neuroblastoma [NB]) to determine its diagnostic and prognostic significance. Materials and Methods: A prospective case–control study was done for 3 years (December 2020 to November 2023) at our institute. All children aged 1 day to 18 years admitted with the diagnosis of NB and nephroblastoma (Wilms’ tumor [WT]) were included after parental consent. The control group includes children of varying ages without any malignancy. Blood and urinary samples were collected at admission before or a week after the biopsy and the level of bFGF and VEGF was analyzed with the ELISA method. Triple-phase computed tomographies along with recommended evaluation were performed according to the tumor as per international standard protocols. Appropriate statistical analyses were done. Results: A total of 30 patients were included in the cohort, of which 13 patients were with the diagnosis of WT. Only 7 patients had metastatic disease. All the patients were treated with neoadjuvant chemotherapy, surgery, and radiotherapy according to their presentation and tumor stage. Both the growth factors, i.e., VEGF (median value - 314.38 pg/mL) and bFGF (median value - 18.96 pg/mL), are elevated in all the tumor patients in comparison with the controls (median VEGF - 100.51 pg/mL and bFGF - 15.6 pg/mL). When compared with the tumor size, no significant associations are found (with VEGF P - 0.40 and with bFGF P - 0.44). Conclusion: Although no satistically significant correlations were found between serum/urinary levels of bFGF and VEGF with tumor size, this study showed the raised median serum value of bFGF and VEGF in patients with NB and WT in comparison to controls and provided the rationale to explore this issue on a larger group of patients.

Deep Learning and Multidisciplinary Imaging in Pediatric Surgical Oncology: A Scoping Review.

Medical images play an important role in diagnosis and treatment of pediatric solid tumors. The field of radiology, pathology, and other image-based diagnostics are getting increasingly important and advanced. This indicates a need for advanced image processing technology such as Deep Learning (DL). Our review focused on the use of DL in multidisciplinary imaging in pediatric surgical oncology. A search was conducted within three databases (Pubmed, Embase, and Scopus), and 2056 articles were identified. Three separate screenings were performed for each identified subfield. In total, we identified 36 articles, divided between radiology (n = 22), pathology (n = 9), and other image-based diagnostics (n = 5). Four types of tasks were identified in our review: classification, prediction, segmentation, and synthesis. General statements about the studies'' performance could not be made due to the inhomogeneity of the included studies. To implement DL in pediatric clinical practice, both technical validation and clinical validation are of uttermost importance. In conclusion, our review provided an overview of all DL research in the field of pediatric surgical oncology. The more advanced status of DL in adults should be used as guide to move the field of DL in pediatric oncology further, to keep improving the outcomes of children with cancer.

ADGRL4 Promotes Cell Growth, Aggressiveness, EMT, and Angiogenesis in Neuroblastoma via Activation of ERK/STAT3 Pathway.

Neuroblastoma (NB) is one of the most common pediatric solid tumors. Emerging evidence has indicated that ADGRL4 can act as a master regulator of tumor progression. In addition, it is well documented that the ERK/STAT3 signaling pathway can promote the proliferation, EMT, angiogenesis, and metastasis in tumors. The current study was formulated to elucidate the exact role of ADGRL4 in the malignant behaviors of NB cells and to investigate the intrinsic mechanism. In this work, expression differences of ADGRL4 in human NB cell lines and HUVECs were assessed via RT-qPCR and western blot analysis. For functional experiments, sh-ADGRL4 was transfected into SK-N-SH cells to generate ADGRL4 knockdown stable cell line. Moreover, ADGRL4 knockdown stable SK-N-SH cells were treated with LM22B-10 (an ERK activator) for rescue experiments. CCK-8 colony formation determined NB cells' growth, migration, invasion, wound healing, and transwell assays. Meanwhile, proliferation-, metastasis- and EMT- associated proteins were also detected. Additionally, a tube formation assay was employed to evaluate in vitro angiogenesis. VM-cadherin, the marker of angiogenesis, was assessed using immunofluorescence staining. Data showed notably upregulated ADGRL4 in NB cells, especially in SK-NSH cells. ADGRL4 knockdown inhibited NB cell growth, migration, invasion, EMT, and in vitro angiogenesis. ADGRL4 knockdown inactivated ERK/STAT3 signaling pathway. Activation of the ERK/STAT3 signaling pathway partially rescued the tumor suppression effects of ADGRL4 knockdown on NB cells. To conclude, the downregulation of ADGRL4 may inhibit cell growth, aggressiveness, EMT, and angiogenesis in NB by inactivating the ERK/STAT3 signaling pathway.

Current trends in intraoperative neurophysiological monitoring among Asia-Pacific countries: an Asia-Pacific Spine Society survey.

A prospective web-based survey. Although intraoperative neurophysiological monitoring (IONM) is critical in spine surgery, its usage is largely based on the surgeon's discretion, and studies on its usage trends in Asia-Pacific countries are lacking. This study aimed to examine current trends in IONM usage in Asia-Pacific countries. IONM is an important tool for minimizing neurological complications and detecting spinal cord injuries after spine surgery. IONM can be performed using several modalities, such as transcranial electrical stimulation-muscle evoked potentials (Tc-MEP) and somatosensory evoked potentials (SEP). Spine surgeons of the Asia-Pacific Spine Society were asked to respond to a web-based survey on IONM. The questionnaire covered various aspects of IONM, including its common modality, Tc-MEP details, necessities for consistent use, and recommended modalities in major spine surgeries and representative surgical procedures. Responses were received from 193 of 626 spine surgeons. Among these respondents, 177 used IONM routinely. Among these 177 respondents, 17 mainly used SEP, whereas the majority favored Tc-MEPs. Although a >50% decrease is the commonly used alarm point in Tc-MEP, half of the Tc-MEP users had no protocols planned for such scenarios. Moreover, half of the Tc-MEP users experienced complications, with bite injuries being the most common. Most respondents strongly recommended IONM in deformity surgery for pediatric and adult populations and tumor resection surgery for intramedullary spinal cord tumors. Conversely, IONM was the least recommended in lumbar spinal canal stenosis surgery. Spine surgeons in Asia-Pacific countries favored IONM use, indicating widespread routine utilization. Tc-MEP was the predominant modality for IONM, followed by SEPs.

Paediatric Central Nervous System Tumours: Symptomatology and Total Diagnostic Interval in a New Zealand Cohort

ABSTRACTBackgroundCentral nervous system (CNS) tumours are the leading cause of paediatric oncologic death and survivors face high rates of persistent disability. Timeframe from initial symptom to diagnostic radiography [total diagnostic interval (TDI)] is associated with increased morbidity and mortality. Interventions such as HeadSmart and Brain Pathways Guidelines UK have reduced TDI in the United Kingdom through public and professional education campaigns.AimsThe overarching aim of this project is to reduce TDI for brain tumours across New Zealand. As there are no local data for TDI in paediatric CNS tumours, we sought baseline data prior to local interventions, which would then inform interventions in the next project phase.MethodsRetrospective analysis of patients ≤ 18 years with a CNS tumour in the ZZ catchment between 2015 and 2020. Demographics, tumour type, presenting symptoms/signs, referral pathways and TDI were recorded.ResultsOf 72 cases, median TDI was 9 weeks (0–156 weeks). This was lower in patients aged &lt; 4 years compared with &gt; 4 years (4 weeks vs. 13 weeks), in high grade tumours compared to low grade (4 weeks vs. 13 weeks), and in other ethnicities compared with Māori/Pasifika (6 weeks vs. 16.5 weeks) (p &lt; 0.05 for all comparisons). Symptomatology was similar to Brain Pathways, however, some signs including head circumference were poorly recorded and identify areas for improvement.ConclusionsMedian TDI is higher than recommended targets, and there is ethnic disparity. This gives impetus for local intervention, using strategies comparable to Brain Pathways.

Asynchronous Transitions from Hepatoblastoma to Carcinoma in High-Risk Pediatric Tumors.

Most malignant hepatocellular tumors in children are classified as either hepatoblastoma (HB) or hepatocellular carcinoma (HCC), but some tumors demonstrate features of both HB and HCC1-3. These tumors have been recognized under a provisional diagnostic category by the World Health Organization and are distinguished from HB and HCC by a combination of histological, immunohistochemical, and molecular features4-6. Their outcomes and cellular composition remain an open question7-9. The heterogeneous histological and molecular profiles of hepatoblastomas with carcinoma features (HBCs)4 may result from cells with combined HB and HCC characteristics (HBC cells) or from mixtures of cells displaying either HB or HCC signatures. We used multiomics profiling to show that HBCs are mixtures of HB, HBC, and HCC cell types. HBC cells are more chemoresistant than HB cells, and their chemoresistance-a driver of poor outcomes10-12-is determined by their cell types, genetic alterations, and embryonic differentiation stages. We showed that the prognosis of HBCs is significantly worse than that of HBs. We also showed that HBC cells are derived from HB cells at early hepatoblast differentiation stages, that aberrant activation of WNT-signaling initiates HBC transformation, and that WNT inhibition promotes differentiation and increases sensitivity to chemotherapy. Furthermore, our analysis revealed that each HBC is the product of multiple HB-to-HBC and HBC-to-HCC transitions. Thus, multiomics profiling of HBCs provided key insights into their biology and resolved major questions regarding the etiology of these childhood liver tumors.

A bibliometric analysis of research trends and hotspots of pilocytic astrocytoma from 2004 to 2023

Pilocytic astrocytoma (PA) is a WHO grade I neoplasm with a favorable prognosis. It is the most common pediatric benign tumor. Recently, PA has attracted more and more attention and discussion from scholars. The aim of this study is to comprehensively generalize the evolution of this field over the past two decades through bibliometric analysis and to predict future research trends and hotspots. The literature over the last two decades (2004–2023) related to PA was obtained from the Web of Science Core Collection (WoSCC) database. Bibliometric analyses were conducted based on the following aspects: (1) Annual publication trends; (2) Publications, citations/co-citations of different countries/institutions/journals/authors; (3) the map of Bradford’s Law and Lotka’s Law for core journals and author productivity; (4) Co-occurrence, cluster, thematic map analysis of keywords. All analyses were performed on VOSviewer and R bibliometrix package, and Excel 2024. Our results showed that research on PA displayed a considerable development trend in the past 20 years. The USA had a leading position in terms of scientific outputs and collaborations. Meanwhile, German Cancer Research Center contributed the most publications. Child's Nervous System had the highest number of publications and Acta Neuropathologica was the most co-cited journal on this subject. Gutmann, D.H. and Louis, D.N. were the authors with the most articles and co-citations in this field. The research emphases were molecular mechanisms, neurofibromatosis, pilomyxoid astrocytoma, differential diagnosis, and therapy. We systematically analyzed the literature on PA from a bibliometric perspective. The demonstrated results of the knowledge mapping would provide valuable insights into the global research landscape.