bluuebunny/crossref_metadata_2025_split huggingface dataset:
SURG-02. INITIAL MANAGEMENT OF HYDROCEPHALUS IN THE PEDIATRIC AND YOUNG-ADULT PATIENTS WITH BRAIN TUMORS; THE EFFICACY OF LONG-TERM INDWELLING EXTERNAL VENTRICULAR DRAINAGE
Authors: Yamaguchi Shigeru , Motegi Hiroaki , Ishi Yukitomo , Okamoto Michinari , Iguchi Akihiro , Cho Yuko , Sugiyama Minako , Manabe Atushi , Houkin Kiyohiro 
Published: December 2020

Abstract

BACKGROUND
Pediatric and Young-Adult (AYA) brain tumors often present with hydrocephalus. As temporary cerebrospinal fluid (CSF) diversion procedure, we perform long-term indwelling external ventricular drainage (EVD) in the case of the management of CSF diversion more than two weeks presumably. The aim of this study is to investigate the initial management for hydrocephalus in pediatric /AYA patients with brain tumor, especially about long-term EVD.

MATERIALS AND METHODS
The patients less than 30 years of age diagnosed with brain tumor between 2005 and 2019 were retrospectively analyzed. Procedures of long-term EVD were similar to that of ventriculoperitoneal shunt (VPS) operation. Using flow-control VPS system, peritoneal catheter passed out of the body at the anterior chest, and distal end of the catheter was connected to standard EVD system.

RESULTS
In total of 345 patients with brain tumor, 109 had hydrocephalus at presentation. Among them, 25 patients (23%) underwent long-term EVD. The main reasons for selecting long-term EVD were to avoid intraperitoneal dissemination (n=13), and to maintain longer period of CSF diversion for the treatment of tumor (n=12). The median of long-term EVD was 38 days (range: 12 – 222 days). Although one case suffered from drainage tube occlusion at 59 days, there were no other complications such as infection or accidental evulsion. Eventually, 3 cases required permanent VPS for persistent hydrocephalus.

CONCLUSION
Long-term EVD is safe and effective option for CSF diversion. This procedure should be taken into consideration if patients have a risk of dissemination and may elude permanent VPS.
SURG-07. CEREBELLAR PEDUNCLE TUMORS IN PEDIATRIC NEUROSURGERY: FEW CITATIONS FOR BEING RARE OR FOR LACK OF AWARENESS
Authors: Sanders Felipe Hada , Matushita Hamilton 
Published: December 2020

Abstract
We present a case-series of 6 pediatric patients, with a follow-up for a minimum of 1 year, with a diagnostic, therapeutic and prognostic description. This type of disease was first mentioned by Professor Tomita in 1986, in a case-series with 4 patients, with few citations in literature, no other case series cited at the literatures. and in our oncology center of excellence it is an entity that draws attention for diverging from intrinsic tumors of the cerebellum, fourth ventricle and trunk. In this way, we created an algorithm approaching these patients and would like to present this associated to honouring the esteemed professor in neurosurgery.
SURG-08. SUPRASELLAR DERMOID CYST IN A PEDIATRIC PATIENT
Authors: Almeida Carlos , Mançano Bruna Minniti , Almeida Gisele Caravina , Eugui Gilda D’Agostino , Cavalcante Carlos Bezerra 
Published: December 2020

Abstract

BACKGROUND
Intracranial dermoid cysts (DC) are rare congenital non-neoplastic lesions that account for 0.04 – 0.6% of all intracranial tumors. They are formed by a fibrous capsule composed of epidermal and dermal derivatives (hair follicles, sebaceous and sweat glands), enclosing a viscous fluid. Intradural DC often arise in the midline and are more common in infratentorial locations. CASE REPORT: A 14-year-old male patient presented with headache, partial motor seizures and behavioral changes. Neurological examination and endocrine workup revealed no abnormalities. Brain magnetic resonance imaging showed a lesion that was 4.4cm x 2.2cm x 4.4cm in size, located at supraselar region, and extended superiorly to the left lateral ventricle and anterolaterally to the left orbitofrontal lobe, associated with hyperintense fat droplets in the right lateral ventricle. We performed a left transventricular microsurgical approach. The tumor capsule was coagulated and opened and a subtotal resection with peacemeal removal of the the lesion was obtained: it had gelatinous consistency, composed of droplets of fat and hair and keratinized scamous epihelium content. A total removal of the DC capsule was not possible due to its firm adherence to optic chiasm and to hypothalamus. Histological examination revealed dermoid cyst.

CONCLUSION
Surgery is the only effective treatment, and its goal should be the radical resection of the lesion to avoid recurrence. Whenever radical resection is not possible, because of the adhesions of the cyst capsule to surrounding tissues, a subtotal resection with piecemeal removal may be a satisfactory option in such cases to avoid high morbidity.
SURG-12. PAEDIATRIC BRAIN TUMOUR SURGERY: HOW CAN WE REPORT OUR SURGICAL OUTCOMES AND OPERATIVE MORBIDITY?
Authors: Foster Mitchell , Hennigan Dawn , Greystone Rebecca , van Baarsen Kirsten , Sunderland Geraint , Millward Christopher , Srinivasan Harishchandra , Ferguson Deborah , Totimeh Teddy , Pizer Barry , Mallucci Conor 
Published: December 2020

Abstract

OBJECTIVE
Our objective was to quantify resection outcomes and operative morbidity in paediatric brain tumour surgery using existing scales, assessing their applicability.

METHODS
We investigated morbidity using the Clavien-Dindo (CD) scale and the Drake classification. All paediatric patients receiving a biopsy or craniotomy for an intracranial tumour in a single tertiary paediatric neurosurgery centre between January 2008 and December 2018 were studied. Complications up to day 30 post op were graded.

RESULTS
There were 459 operations: 92 biopsies and 367 craniotomies comprising 166 infratentorial and 292 supratentorial tumours. Median age was 9 years (56% male). The surgical goal was achieved or exceeded in 94% of cases. Thirty-day mortality was 1.31% with all deaths related to disease and none to surgical complications. The overall CD score was 1 in 10.9% of cases, 2 in 18.9%, 3A in 1.7%, 3B in 11.8%, and 4 in 1.1%. There was no operative morbidity in 54% of cases. Using the Drake classification, meningitis was seen in 3.92% of cases, seizures in 3.92%, neurological deficit (that persisted at 30 days) in 8.5%, CSF leak in 5.01%, wound infection in 1.96%, haemorrhage 1.75 %, shunt infection in 1.53%, shunt block in 0.65%, medical complications in 2.4%, and others in 3.05%.

CONCLUSIONS
This is the largest series presenting morbidity from paediatric brain tumour surgery, and the first to validate the CD scale. Our morbidity on the Drake scale was comparable with other series. There is a need to develop improved tools to quantify morbidity in this high-risk specialty.
SURG-20. DIENCEPHALIC SYNDROME IN PEDIATRIC NEUROSURGERY
Authors: Sanders Felipe Hada , Matushita Hamilton , Azambuja Alessandra , Frasseto Fernando 
Published: December 2020

Abstract
This report details the histories of twelve patients with clinical diencephalic syndrome who collectively demonstrate the variability found in the syndrome with respect to: (1) clinical course, (2) site of the tumor, and (3) ease of obtaining radiologic confirmation of the presence of a tumor. Timely diagnosis of diencephalic syndrome is not often the case for patients presenting with failure to thrive (FTT) because of its rarity and lack of specific symptoms. These cases illustrate the importance of cranial imaging and consideration of diencephalic syndrome for children presenting with FTT despite normal or increased caloric intake.
SURG-21. ENDO- AND EXOSCOPIC SURGERY FOR PEDIATRIC NEUROSURGICAL OPERATION
Authors: Kurozumi Kazuhiko , Kameda Masahiro , Fujii Kentarou , Shimazu Yosuke , Yasuhara Takao , Date Isao 
Published: December 2020

Abstract

INTRODUCTION
Recently endo- and exoscopic surgeries have been gradually performed in neurosurgery. To improve the accuracy and safety of our endoscopic procedures, we are currently trialing 4K or 8K systems. Here we report our experience of endo- and exoscopic procedures for pediatric neurosurgery.

METHODS
We retrospectively identified 22 patients (15 males, 7 females; mean age, 9.2 years) who underwent surgery for sellar lesions and intraventricular or intraparenchymal lesions with an endo- or exoscopic procedure at our institute between 2010 and 2020. We used a full HD endoscope system (Storz) and an organic electroluminescence (EL) monitor (Sony), and a 4K system (Sony and Olympus). VITOM 3D (Storz) was used as the exoscope. Videoscope (Olympus) was used as a flexible scope for intraventricular tumors.

RESULTS
We performed surgical procedures as 11 biopsies, 6 third ventriculostomies, 5 resections, and 3 fenestrations. The full HD system with organic EL monitor presented high color contrast. We could easily distinguish between tumor microstructure and the normal structure with the 4K system comparing to full HD. Moreover, electronic zoom function enabled us to discriminate tumor boundaries without having to move the endoscope closer. As a result, we could delineate the surgical working space. VITOM 3D was simple to sharpen the focus on the wider surgical field, similar to the application of an operating microscope.

CONCLUSION
In pediatric neurosurgery, an endo- or exoscope enables clear visual recognition of a boundary between tumor and normal area.
TBIO-03. THE GIFT FROM A CHILD PROGRAM IS EMPOWERING POST-MORTEM TISSUE DONATION ACROSS THE UNITED STATES
Authors: Waanders Angela , Williams Melissa , Wadwhani Nitin , Li Xiao-Nan , Goldman Stewart , Tran-Du Kella , Minturn Jane , Mason Jennifer , Santi Mariarita , Viaene Angela , Koptyra Mateusz , Monje-Deisseroth Michelle , Nazarian Javad , Kambhampati Madhuri , Eze Augustine , Souweidane Mark , Lyons Nicole , McLean Ginny , Gustafson Patti , Gustafson Allen 
Published: December 2020

Abstract
The Gift from a Child (GFAC) program was inspired by the dream of one child to donate his brain for research, recognizing the need to study tumor tissue collected at diagnosis, recurrence, and at the time of death. Founded by the Swifty Foundation in 2016, GFAC currently is comprised of five “Centers of Excellence” at institutions with expertise in pediatric neuro-oncology. Partnering with the Children’s Brain Tumor Network, the program’s mandate is twofold: make it possible for families to donate no matter where they live in the United States and make tissue available to scientists globally to empower discovery. In order to overcome barriers that have stifled postmortem collection in the past, GFAC has invested in Tissue Navigators - individuals at each center who coordinate all aspects of donation and communicate with families, medical providers, and laboratory scientists. In 2019 alone, GFAC coordinated 55 autopsy collections from multiple diagnosis. A key metric of the program is also capturing the global sharing and usage of each tissue sample, ensuring that tissue isn’t simply “banked” but is actively being actively used to help unravel tumor biology. To date, tissue has been used for genomic and molecular data generation, preclinical model development including cell lines and PDX models, and for novel drug screening. Together with Children’s Brain Tumor Network, the Gift from a Child program is helping to ensure the most precious gift that a family can make is used to accelerate the path to cures.
TBIO-05. GENOME-SCALE NUCLEOTIDE-SPECIFIC CHARACTERIZATION OF 5-HYDROXYMETHYLCYTOSINE IN PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS
Authors: Azizgolshani Nasim , Petersen Curtis L , Salas Lucas , Chen Youdinghuan , Perreard Laurent , Nguyen Lananh N , Christensen Brock C 
Published: December 2020

Abstract
Though aberrant cytosine modifications are prevalent in cancer, nucleotide-specific 5-hydroxymethylcytosine (5hmC) modifications remain understudied, including in pediatric CNS tumors. Brain 5-hydroxymethylation is linked with development and differentiation. We measured genome-scale nucleotide-specific 5hmC in patients with diagnoses of glioma, ependymoma, and embryonal tumors under age 18 (n=36), and in non-tumor pediatric brain tissues (n=3). DNA was processed with tandem oxidative (OxBS) and bisulfite (BS) treatments followed by hybridization to the Illumina Methylation EPIC Array that interrogates over 860,000 CpG sites. We used the OxyBS R package to determine levels of 5hmC and 5mC. Mean 5hmC levels were lower in tumors (gliomas 4.1%, ependymomas 3.9%, and embryonal tumors 3.4%) compared to nontumor tissues (5.3%). We subset to the CpGs with the 5% highest 5hmC content for downstream analyses (37,173 CpGs). These sites were enriched among regulatory elements, including TFBS (Odds Ratio 1.14 p-value 3.57E-20) and super-enhancers (OR 1.93, p-value 1.14E-126). Linear mixed-effects models adjusted for age, sex, and cell type proportions tested the CpG-specific differences in 5hmC between tumor and nontumor samples, as well as between tumor subtypes. 5hmC levels were depleted across tumors compared with nontumor brain tissues, including at CpG islands. Model-based clustering (RPMM) results indicated that patients with low 5hmC patterns have poorer overall survival and increased risk of recurrence. Our results indicate that 5hmC localizes to sites in the DNA critical to gene regulation and is associated with patient outcomes. This study offers an opportunity to potentially contribute to classification markers for childhood brain tumors.
TBIO-12. THE SPECTRUM OF MITOCHONDRIAl DNA (mtDNA) MUTATIONS IN PEDIATRIC CENTRAL NERVOUS SYSTEM (CNS) TUMORS
Authors: Kaneva Kristiyana , Triska Petr , Merkurjev Daria , Bootwalla Moiz , Cotter Jennifer , Ostrow Dejerianne , O’Halloran Katrina , Biegel Jaclyn , Gai Xiaowu 
Published: December 2020

Abstract
To explore the role of mitochondrial DNA mutations in pediatric CNS tumors, we analyzed 749 tumor-normal paired whole genome sequencing data sets from the Children’s Brain Tumor Tissue Consortium (CBTTC). We detected 307 somatic mtDNA mutations in 222 CNS tumors (29.6%). Most frequently observed were missense mutations (38.1%). We also detected 34 loss-of-function mutations. Different pediatric CNS tumor subtypes have distinct mtDNA mutation profiles. For categorical comparisons, we analyzed subtypes with at least 15 samples. The highest number of mtDNA mutations per tumor sample was in meningiomas (0.85), while atypical teratoid rhabdoid tumors (ATRTs) had the lowest number per sample (0.18). High-grade gliomas had a higher number of mtDNA mutations per sample than low-grade gliomas (0.56 vs. 0.31) (p = 0.0011), with almost twice as many missense mtDNA mutations per sample (0.22 vs. 0.13) (p &lt; 0.001), and higher average heteroplasmy levels (11% vs. 9%). The average heteroplasmy was 10.1%, ranging from 15.6% in medulloblastoma to 6.36% in schwannoma suggesting that these are clonal alterations and not artifacts. Intriguingly, the two chordoma patients in the CBTTC database had an identical heteroplasmic m.10971G&gt;A MT-ND4 nonsense mutation. Similarly, our patient with recurrent gliofibroma harbored the same somatic MT-ND4 synonymous variant (m.10700A&gt;G) detected at 53% heteroplasmy in the initial tumor, 79% in the first recurrence, and 97% in the second recurrence. Although the functional consequences of these alterations are not yet understood, our findings suggest that sequencing the mtDNA genome may be used to characterize CNS tumors at diagnosis and monitor disease progression.
TBIO-13. USE OF NEXT GENERATION SEQUENCING TO IDENTIFY MOVE DRIVERS OF CRYPTIC, CLINICALLY AGGRESSIVE BRAIN TUMORS
Authors: Younes Subhi Talal , Boudreaux Amanda , Weaver Kristin , Karlson Cynthia , Herrington Betty 
Published: December 2020

Abstract

INTRODUCTION
Next generation sequencing (NGS) is an emerging technology which allows for in-depth analysis of pediatric brain tumors. NGS has particular use in the context of ambiguous or aggressive neoplasms, where it can be leveraged to discover novel drivers, inform pathologic classification, and direct targeted therapies.

OBJECTIVE
The objective of this case series was to utilize NGS technology to illuminate the biology of aggressive brain tumors with ambiguous pathologic features and clinically aggressive behavior.

METHODS
FFPE tumor tissue and matched germline DNA were subjected to whole exome sequencing (WES). Data were analyzed according to the GATK pipeline.

RESULTS
The first case is a 6-year-old male who presented with innumerable foci of leptomeningeal nodules throughout the neuroaxis. Original pathology was CNS embryonal tumor. WES identified loss of chromosome 1p and 16q with gain of 1q and amplification of MYC and OTX2 loci (cytogenetic aberrations characteristic of group 3 medulloblastoma) and a deleterious mutation in BCL7B, a known tumor suppressor gene. The second case is a 2-year-old female who presented with a parietal lobe mass diagnosed as high grade neuroepithelial tumor with C11orf95 translocation, but no RELA fusion. WES revealed loss of small region of chromosome 2p and mutations in IDH3G, TRAF2, and JMJD1C, suggesting novel targets for further study.

CONCLUSIONS
In both cases, NGS studies were able to shed light on the underlying tumor biology and/or refine the pathologic diagnosis. These data underscore the utility of applying NGS technology to study the biology of pediatric brain tumors.
TBIO-14. CHARACTERISATION OF THE ARGININE PATHWAY ENZYMES IN PAEDIATRIC BRAIN TUMOURS TO DETERMINE SUSCEPTIBILITY TO THERAPEUTIC ARGININE DEPLETION
Authors: Bishop Eleanor , Dimitrova Monika , Storer Lisa , Grundy Richard , Dandapani Madhumita 
Published: December 2020

Abstract

INTRODUCTION
Extracellular arginine dependency (auxotrophy) is increasingly being recognised in several tumours. This is due to the inability of cancer cells to recycle or synthesise intracellular arginine through the urea cycle pathway compared to normal cells. Whilst adult glioblastoma is known to exhibit this, the expression of the arginine pathway enzymes has not been delineated in paediatric brain tumours.

METHODS
We used immunohistochemical methods to stain for arginine pathway enzymes in Paediatric High grade glioma (pHGG), low grade glioma (pLGG) and medulloblastoma (MB) tumour tissue microarrays (TMAs). The antibodies detected protein expression of the metaboliser Arginase (Arg2), recycling enzymes ornithine transcarbamoylase (OTC), Arginosuccinate synthetase (ASS1) and arginosuccinate lyase (ASL) as well as the transporter SLC7A1.

RESULTS
Deficiency of OTC, ASS1 and ASL were seen in 92%, 98% and 93% of pHGG samples (n=156) respectively, with deficiency defined as low (&lt;20%) or negative antibody expression. Identical results were seen in pLGG (n=98) - 83%, 97% and 95% were deficient in OTC, ASS1 and ASL. Both pHGG and pLGG highly expressed SLC7A1 and Arg2, demonstrating that they could transport and utilise arginine. In MB (n=82), this auxotrophic signature was again seen in 90% of TMAs with absent or low expression of OTC, ASS1 and ASL and high Arg2 and SLC7A1 expression.

CONCLUSIONS
These results show that pHGG, pLGG and MB are arginine auxotrophs. Pegylated arginase (BCT-100) is currently in Phase I/II trials in relapsed pHGG. Our results suggest that therapeutic arginine depletion may also be useful in MB and pLGG.
TBIO-15. MODELING DEVELOPMENTAL GENE EXPRESSION DYNAMICS AT CELLULAR RESOLUTION TO INTERPRET PEDIATRIC BRAIN TUMOR TRANSCRIPTIONAL PROGRAMS
Authors: Jessa Selin , Kabir Nisha , Vladoiu Maria , Hébert Steven , Taylor Michael D , Jabado Nada , Kleinman Claudia L 
Published: December 2020

Abstract
A central challenge in understanding the biology of pediatric brain tumors is defining the cellular and molecular context where oncogenesis occurs. We hypothesize that spatiotemporally restricted cell types are uniquely susceptible to specific genetic alterations, which alter normal neurodevelopmental programs and ultimately lead to oncogenesis. The resulting tumors retain some transcriptomic features of their lineage of origin. To delineate these origins, we assembled a densely sampled developmental time course of the mouse forebrain and pons, doubling our recently published single-cell atlas. This dataset comprises &gt;100,000 cells at 9 timepoints from E10-P6. However, while single cell transcriptomics reveal rich gene dynamics during cell differentiation, interpretation of individual genes can be challenging due to data sparsity. Leveraging this time-series, we present strategies to model and visualize the expression of a given gene across differentiation of distinct lineages. We demonstrate an interactive web app to interrogate the expression of genes or gene sets during brain development, extract temporally correlated genes, and search active transcription factor regulatory modules. Finally, we profile the expression of core transcriptional programs of several pediatric brain tumor entities during development. Our analyses reveal genes with restricted expression patterns that elucidate tumor etiology. More broadly, these resources harness single cell data to enable exploration of neurodevelopmental gene programs with great relevance to pediatric brain tumor oncogenesis.
TBIO-16. NOTCH1 PATHWAY AS TARGET FOR DRUG INTERVENTION FOR HISTONE 3 G34R MUTATED pHGG
Authors: Foot Katie , Lourdusamy Anbarasu , Christou Sofia , Rahman Ruman , Layfield Robert , Grundy Richard , Haque Farhana 
Published: December 2020

Abstract
There have been no significant improvements in the treatments for childhood High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), which continue to have a very poor prognosis. These cancers harbor mutations affecting histone 3 (H3) proteins; 80% of DIPGs with histone H3 K27M somatic mutations whilst 30% of pHGGs exhibit H3.3 G34R or G34V mutations. We have generated and validated a histone 3.3 G34R mutant-specific antibody and investigated the downstream effects of H3.3 G34R mutations in pHGG. In order to identify the genes that may be deregulated by G34R mutant histone expression, we have performed chromatin immunoprecipitation (ChIP) assays with our H3.3 G34R and wild type H3 antibodies, using pHGG H3 G34R mutant and wild-type cell lines. Initial analyses of ChIP data have implicated deregulation of cell-signaling pathways including Notch1, Hedgehog, PPAR-1, PLC-beta and Androgen, in H3 G34R mutated pHGG. We are currently determining the effects of altered expression of Notch1 pathway components on tumorigenesis of H3 G34R mutated pHGG, through gene and protein expression and inhibition assays. Specifically we find that the Notch1 pathway component HES1 shows increased expression in G34R mutant cells compared to controls, directing our evaluation of the utility of gamma-secretase inhibitors as potential therapeutics. These analyses may underpin development of novel treatment strategies for H3 mutated pHGG.