tbuckley/cabot-search huggingface dataset:
CRAN-31. PAPILLARY CRANIOPHARYNGIOMA WITH BRAF V600E MUTATION IN A FOUR YEAR OLD CHILD: A CASE REPORT AND REVIEW OF CLINICAL CASES FROM LITERATURE
Authors: Roisin Borrill, Anthony Penn, Edmund Cheesman, Stavros Stivaros, Ian D Kamaly-Asl, Kanna Gnanalingham, John-Paul Kilday
Journal: Neuro-Oncology (2018)

We report a four year old girl with autistic spectrum disorder who was being investigated for symptomatic central hypothyroidism and potential growth hormone deficiency. Brain MR imaging revealed a large solid / cystic suprasellar mass, splaying the optic chiasm and measuring 3 x 1.9 x 2.3 centimeters. The pituitary was obscured, other than a small portion of the infundibulum. The patient underwent a transphenoidal near total resection of the lesion, with necrotic cream-like material being encountered within the tumour bed. Post-operatively the patient developed transient diabetes insipidus but otherwise recovered well. The pathology of the lesion was consistent with a papillary craniopharyngioma with regions of stratified squamous epithelium accompanied by superficial goblet cells and ciliated cells. Subsequent next generation sequencing analysis of the lesion confirmed the presence of a BRAF V600E mutation (BRAFc.1799T>A p. (Val600Glu). To date, she has had no further therapy and remains stable nine months following surgery. LITERATURE REVIEW, METHODS AND Clinical cases of pediatric papillary craniopharyngioma were identified for those aged below 16 years via OVID and Pubmed search engines using clearly defined terms. Cases meeting the inclusion criteria are presented. We present one of the youngest patients published with a papillary craniopharyngioma, confirmed using histological and molecular analysis. This tumour type is extremely uncommon in the very young and encourages discussion about the most appropriate adjuvant therapy for tumour progression in such children, given the risks of radiotherapy to the developing brain and the increasing availability of oral BRAF inhibitor therapy.
Targeted-sequencing and comprehensive molecular profiling of gastric signet ring cell carcinoma
Authors: J. Wei, N. Wu, Y. Wang, B. Xu, Y. Yang, J. Du, L. Yu, Z. Zou, Y. Shao, S. Zhu, B. Liu
Journal: Annals of Oncology (2018)

Introduction: Gastric cancer is a heterogeneous disease with various molecular subtypes. Signet ring cell carcinoma is characterized by a highly malignant phenotype of gastric cancer with no known effective molecularly targeted therapies. The limited knowledge of the molecular mechanisms underlying signet ring cell carcinoma hinders the development of therapeutic strategies. Methods: We performed a targeted sequencing panel focusing on 416 genes in 70 gastric signet ring cell carcinoma (SRCC) tumor-normal pairs, for integrative genomic analysis. This gene panel is composed of 416 cancer-related genes which can test a wide range of genetic abnormalities including point mutations, fusions, insertions, deletions and amplifications. Furthermore, this panel covers all currently available molecular-targeted & chemotherapy drugs, and ongoing clinical trials. Results: We identified previously well-known oncogenes and tumor suppressor genes mutation, including chromatin remodeling genes CDH1 (17%), ARID1A (9%), BRCA1 (6%), CHD4 (6%), SMARCA4 (4%), TP53 (27%) dysregulation, activation of receptor tyrosine kinases genes ERBB3 (9%), PIK3CA (7%), PTEN (6%), MTOR (4%), ERBB2 (4%), ERBB4 (3%), FGFR2 (3%), FGFR4 (3%), stem cell pathways genes TGFBR2 (6%), APC (3%), and others. Meanwhile, we observed new significantly mutated genes in SRCC. Specifically, gene PKHD1 (16%), MED12 (16%), STAG2 (10%), KDR (10%), ATRX (9%) were frequently mutated in SRCC tumor samples. However, RHOA mutation was detected only in 4% tumor samples. For DNA copy number profiling, genes including NOTCH1 (16%), FLT4 (9%), CCND1 (7%), HNF1A (6%), CDKN2A (6%), CDKN2B (6%) and RECQL4 (6%), were frequently altered in SRCC. Conclusion: Our genomic landscape revealed SRCC was a distinct entity which harboring different mutational profile to other gastric cancers. Our results may provide potential target for genome-guided personalized therapy in SRCC.
TBIO-28. DISEASEXPRESS, A CANCER DATA ANALYTICS AND VISUALIZATION TOOL FOR IDENTIFYING IMMUNOTHERAPEUTIC TARGETS IN PEDIATRIC BRAIN TUMORS AND OTHER CANCERS
Authors: Pichai Raman, Komal Rathi, Karthik Kalletla, Yuankun Zhu, Bo Zhang, Anthony Cros, Javad Nazarian, Angela J Waanders, Sabine Mueller, Phillip B Storm, Adam C Resnick
Journal: Neuro-Oncology (2018)
TBIO-14. SUBEPENDYMAL GIANT CELL ASTROCYTOMA (SEGA) - A CLINICAL, HISTOPATHOLOGICAL AND MOLECULAR STUDY
Authors: Wieslawa Grajkowska, Joanna Trubicka, Katarzyna Kotulska-Jozwiak, Marcin Roszkowski, Bozenna Dembowska-Baginska
Journal: Neuro-Oncology (2018)

Subependymal giant cell astrocytoma (SEGA) is a most common brain tumor in patients with tuberous sclerosis complex caused by mutation in TSC1 or TSC2 genes. Most of patients present the epilepsy and increased intracranial pressure. The aim of this work was provided a comprehensive analysis of SEGAs, including histopathological features, spectrum of molecular defects and clinical outcome. MATERIAL AND The group of 33 SEGAs patients was included in this study. In all SEGAs microscopic pattern, results of immunohistochemical tests and spectrum of mutations were analyzed and correlated with clinical data, including response of the everolimus treatment. Microscopically SEGAs were composed of large pleomorphic cells with abundant cytoplasm and large nuclei with prominent nucleoli, spindle cells arranged within sweeping fascicles or ganglion-like cells. In four tumors foci of necrosis and mitotic figures were observed. In most of SEGAs focal calcifications were found, in two tumors calcifications were numerous and predominant. Tumors cells were positive for GFAP, S100 and present variable expression for neuronal markers. All of them displayed mTOR immunoreactivity. Most of SEGAs revealed mutations in TSC2 genes, including three tumors with large deletions involving the entire TSC2 and PKD1 region. No histopathological changes were observed in cases after everolimus treatment. SEGAs display heterogeneous histopathological pattern, in some cases with anaplastic features. Tumors in patients with TSC2/PKD1 deletion developed earlier in childhood and presented rapid growth. The response of mTOR inhibitor therapy was not noticed on microscopic level. The study was funding by CMHI project S152/2017.
Gastro-oesophageal reflux and idiopathic pulmonary fibrosis: the heart burn in patients with IPF can no longer be silent
Authors: Michael Kreuter, Ganesh Raghu
Journal: European Respiratory Journal (2018)

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of complex cause affecting an elderly population where multimorbidity is frequent. There is an increasing understanding of the distinct comorbidities over-represented in patients with IPF and associated with a clinically important impact on symptoms and outcomes [1–4]. More than 40 years ago, Mays et al . [5] were the first to describe a potential association between gastro-oesophageal reflux (GOR) and IPF. Since then multiple reports have established that gastro-oesophageal reflux disease (GORD) is one of the most prevalent comorbid conditions in IPF. Based on the increased prevalence, it has been hypothesised that GOR-associated microaspirations may have a pathogenic role in IPF. This stimulated further research, including in animal models, which suggested that aspiration of acid refluxate causes the parenchymal damage associated with pneumonitis and increased epithelial permeability with the consequence of stimulated fibrotic proliferation and perhaps of acute exacerbations (summarised in [6]). Therefore, an early dream was that supressing microaspiration may alter the course of IPF, namely by allowing greater symptom management, disease stabilisation and perhaps improved survival [7]. A prospective, randomised trial is needed to determine the safety and efficacy of anti-acid drugs/proton pump inhibitors in patients with IPF <http://ow.ly/A63330ktoGm>
EPID-16. REVIEW OF CLINICAL PRESENTATION AND DIAGNOSIS INTERVAL IN PEDIATRIC PATIENTS WITH PRIMARY BRAIN TUMOURS IN WESTERN UKRAINE
Authors: Roman Kizyma, Zoryana Kizyma, Bogdan Kotsay, Oleksandra Dvornyak, Iryna Shchurovska, Taras Mykytyn, Konstyantin Biganych
Journal: Neuro-Oncology (2018)

Prolonged time to the diagnosis of brain tumour often has the impact on survivorship as pediatric CNS tumours with late diagnosis may require more aggressive multimodal treatment with surgery, adjuvant radiotherapy and chemotherapy to achieve remission and good quality of life. A retrospective chart review of 108 children with brain tumours of different histological subtypes treated and observed from 2006 to 2015 was performed. The analysis included primary symptoms, performed diagnostic procedures and interval to final diagnosis. Patients were identified from the National cancer registry records and local hospitals charts. Of all cases, 75% had sufficient information to perform analysis of the symptoms, procedures and interval between disease first signs and final diagnosis. The main symptoms were headache, nausea and vomiting, symptoms of cerebellar dysfunction, visual impairment, symptoms of peripheral nerves abnormalitis and different cognitive decline symptoms. The median symptoms-diagnosis interval was 4.5 months. Posterior fossa tumors had the shortest time to final diagnosis (2 months median) due to more symptoms and procedures performed. 30% of patients had final diagnosis in 1 month, 15 % of patients had final diagnosis over 1 year. Only 20% of patients had preliminary diagnosis of brain tumor established by primary physician. Patients with vomiting and headache had the longest symptom-diagnosis intervals and patients with visual abnormalities and cerebellar symptoms had the shortest. Children with tumours of the brain stem had more symptoms than other. Time to final diagnosis affects survival and quality of life and has to be improved.
Morbidity trends for selected gastrointestinal cancers in Poland and the costs of treatment
Authors: M. Jarosz, E. Rychlik
Journal: Annals of Oncology (2018)

Introduction: Gastrointestinal cancers are very prevalent in Poland, although in the last over 20 years there has been a favorable tendency of a decrease in the incidence of most of them. The costs of their treatment are very expensive. The decrease in morbidity allowed to reduce them. The aim of the study was to analyze the dynamics of selected gastrointestinal cancers in Poland and to estimate its influence on the costs of treatment. Methods: The source of data on cancer incidence rates was the National Cancer Registry. The decrease in incidence of selected gastrointestinal cancers in the years 1990-2014 was assessed on the basis of the analysis of trends of potential growth curves and curves of actual, lower morbidity. Information on costs of treatment was derived from Central Statistical Office publications and additional information on these costs was taken from the estimates of Insurance Companies. Results: Since the 1990s the incidence of most cancers of the gastrointestinal tract (gastric, pancreatic, oesophageal, liver and gallbladder) has decreased. Moreover, the growth rate of colorectal cancer is decreasing. It has been estimated that this has resulted in around 188,000 cases of illness less. The greatest reduction in the number of cases reported in gastric cancer - 33% of all cases. The direct costs of treatment of one patient are about 2,400 euro annually. These indirect costs included in the treatment are estimated at around 4,800 euro per year. In total, these costs amount to approx. 7,200 euro annually. The reduction in the number of cases of gastrointestinal cancer in the last 20 years has saved about 1.35 billion euro. Conclusion: In 1990-2014 a significant reduction in the number of cancers of the gastrointestinal tract was noted in Poland. The number of cases of gastric cancer decreased the most. The decline in morbidity for most cancers related to favorable changes in diet and tobacco smoking in Poland contributed significantly to reduce the cost of treatment.
MBRS-40. HMGA2 IS A PROGNOSTIC FACTOR TO INDUCE MALIGNANT PHENOTYPE IN MEDULLOBLASTOMA
Authors: Yoshiki Arakawa, Bin Liu, Yukinori Terada, Yasuzumi Matsui, Etsuko Hattori, Sosuke Sumiyoshi, Nobuyuki Fukui, Masahiro Tanji, Yohei Mineharu, Susumu Miyamoto
Journal: Neuro-Oncology (2018)

Medulloblastoma is the most common of the embryonal tumor arising in the cerebellum and the molecular mechanism of its oncogenesis has been revealed by recent studies. The constitutive expression of high mobility group AT-hook 2 (HMGA2) is associated with a highly malignant phenotype and reduced survival in several malignancies. However, little is known about the clinical and biological significance of HMGA2 in medulloblastoma. In this study, we explore the expression, prognostic and therapeutic role of HMGA2 in medulloblastoma. HMGA1 and HMGA2 expressions were examined using immunohistochemistry in 20 patients with medulloblastoma. To examine the function of HMGA2 expression, knock-down HMGA2 expression was applied in Daoy, D283 and D341 cells. Overexpressions of HMGA1 and HMGA2 were frequently identified in medulloblastoma tissues. In addition, high expression of HMGA2 correlated with high proliferation marker Ki-67 labeling index. High expression of HMGA2 was significantly associated with progression free survival and overall survival of patients with medulloblastoma (p=0.021 and p=0.016, respectively). Functional experiments confirmed that knock-down of HMGA2 resulted in inhibited cell proliferation, migration/invasion and enhanced apoptosis in vitro. In conclusion, HMGA2 overexpression is frequent in medulloblastoma, and its expression is related to proliferation marker and poor prognosis. These findings suggest that HMGA2 could serve as a potential target for future therapeutic strategies in medulloblastoma.
Stop routine screening for associated malignancies in cutaneous noninvasive vulvar Paget disease?
Authors: M. van der Linden, M.S. Schuurman, J. Bulten, L.F.A.G. Massuger, J. IntHout, M.A. van der Aa, J.A. de Hullu
Journal: British Journal of Dermatology (2018)

Vulvar Paget disease (VPD) is extremely rare and thought to be associated with other malignancies.To evaluate the risk of developing breast, intestinal and urological malignancies in patients with VPD compared with the general population, and in particular to focus on the risk of malignancy in patients with cutaneous noninvasive VPD.Data on the oncological history of patients with any type of VPD between 2000 and 2015 were obtained from PALGA, a nationwide archive containing all pathology reports in the Netherlands. Follow-up data and a control group from the general population were obtained from the Netherlands Cancer Registry. After correction for age and calendar year at time of diagnosis, standardized incidence ratios (SIRs) for the first 3 years after VPD diagnosis were estimated with 95% confidence intervals (CIs).We identified 199 patients with a first diagnosis of VPD [164 noninvasive, 35 (micro)invasive] between 2000 and 2015. The SIR of developing an associated malignancy in the first 3 years after diagnosis was 4·67 (95% CI 2·66-7·64). This was due mainly to the high incidence of intestinal malignancies among patients with secondary VPD. Subgroup analysis for cutaneous noninvasive VPD did not reveal a significantly increased risk for associated malignancies: SIR 2·08 (95% CI 0·76-4·62).Of our patients with VPD, 76·9% were diagnosed with cutaneous noninvasive VPD, and this group has no increased risk for developing malignancies of the breast, intestine or urological tract. Our study suggests that routine screening for these malignancies in patients diagnosed with cutaneous noninvasive VPD may not be necessary.
Oxidized lipids keep heat shock chaperones busy: new insights on the deficiencies of tumour-associated dendritic cells
Authors: Paula Nunes-Hasler
Journal: Journal for ImmunoTherapy of Cancer (2018)

In a recent publication in <i>Nature Communications</i> the group of Dr. Dmitry Gabrilovich takes us one step closer to understanding why lipid accumulation impairs the function of tumour-associated dendritic cells (DCs). In this study, the authors present two surprising and significant findings. First, they show that in mouse DCs oxidized lipids function as a sink that traps the heat shock chaperone HSP70, a molecular target of emerging anti-cancer strategies. Secondly, they find that HSP70 in turn regulates the trafficking of peptide-loaded major histocompatibility complex class I (pMHC-I) molecules, a complex that triggers the proliferation of cancer-killing T cells. These observations are discussed briefly in the context of lipid droplet function and pMHC-I trafficking in tumour-associated DCs, as well as HSP70's pleiotropic and incompletely understood roles - and what they mean for future cancer therapy designs.
DIPG-16. DELAYED RT IN SELECT PATIENTS WITH DIPG
Authors: Kevin De Braganca, Viviana Benitez, Stephen Gilheeney, Matthias Karajannis, Yasmin Khakoo, Kim Kramer, Suzanne Wolden
Journal: Neuro-Oncology (2018)

Patients with DIPG sometime present with mild symptoms and/or atypical MRI findings. Since palliative radiation therapy(RT) is the only effective treatment, a decision to treat with RT or wait for progressive symptoms and/or MRI changes arise. Progression free survival(PFS) and overall survival(OS) after delay in RT (>30 days from diagnosis) was compared against patients treated without delay. An IRB retrospective waiver for patients with DIPG treated within Pediatrics at MSKCC from 2000–2016 was obtained. Univariate analysis of days to RT from diagnosis, gender, age, symptom duration, MRI (typical versus atypical) and association with PFS and OS via the Cox proportional hazard model was performed. Patients treated with radio-labeled antibody delivered via convection enhanced delivery were excluded (n=26). Thirty-nine patients with complete records were analyzed, median age: 6.8 years (range: 2–36.5), gender: 19 girls, atypical MRIs: 18. Six patients had delayed RT (days: 32, 33, 42, 74, 77 and 2793). The patient delayed 2793 days had a biopsy at progression demonstrating K27M staining. Patients had varying treatment courses: concomitant chemotherapy with RT, chemotherapy after RT and re-irradiation. Non-delayed versus delayed RT, PFS (6.7mo versus 10.4mo, p=0.184) and OS (12.7mo versus 12.9mo, p=0.485) were not associated with any significant difference. Univariate analysis found no associations. We found no association between delayed initiation of RT and PFS or OS in this retrospective analysis. Our data suggest that in a small subset of patients with DIPG presenting with atypical MRI findings and/or mild symptoms, it may be reasonable to delay initiation of RT.
Gosport hospital: GP prescribed opioids that shortened at least 456 lives
Authors: Clare Dyer
Journal: BMJ (2018)

An independent inquiry into deaths at a Hampshire hospital caring for elderly people has found that at least 456 patients had their lives shortened by being given large doses of opioids that were not medically indicated.1

The investigation found “an institutionalised practice of the shortening of lives through prescribing and administering opioids without medical justification” at Gosport War Memorial Hospital from 1989 to 2000, said James Jones, former bishop of Liverpool, who headed the inquiry panel. Taking into account missing records, probably at least another 200 patients had their lives cut short by the practice, which had become the norm at the hospital, the panel concluded.

A local GP, Jane …
Роль вісцеральної гіперчутливості в розвитку синдрому подразненого кишечника
Authors: Yu.M. Stepanov, I.Ya. Budzak
Journal: GASTROENTEROLOGY (2018)

У статті розглядаються питання патогенеза синдрому подразненого кишечника. Детально розглянуто один з ключових патогенетичних факторів — вісцеральну гіперчутливість. Показані історичні аспекти вивчення, форми та способи оцінки вісцеральної гіперчутливості. Проаналізовані питання взаємовідносин вісцеральної гіперчутливості та інших факторів патогенезу синдрому подразненого кишечника.
GERM-19. DIAGNOSTIC EXPOSURE TO LOW-DOSE RADIATION AND SPONTANEOUS REGRESSION IN INTRACRANIAL GERM CELL TUMORS
Authors: Naoki Kagawa, Ryuichi Hirayama, Shogo Fukuya, Takamune Achiha, Chisato Yokota, Yasuyoshi Chiba, Daisuke Eino, Toru Umehara, Takanori Fukunaga, Manabu Kinoshita, Yasunori Fujimoto, Haruhiko Kishima
Journal: Neuro-Oncology (2018)

Spontaneous regression in intracranial germ cell tumors has been reported in some literatures, but the mechanism has not been well known. We retrospectively measured the tumor volume before chemoradiotherapy and analyzed factors that influence shrinkage of tumor volume. PATIENTS AND Thirty-nine cases with primary intracranial germinomas and HCG-producing germinomas were treated in our hospital from 1994 to 2017. In twenty-one of them, plural MRI scans were done before the first course of chemotherapy regimen. Their age ranged from 8 to 31 years. Three cases were bifocal type, one case had multiple lesions. Biopsies were performed in all regions. Tumor volume of twenty-four lesions was analyzed by volumetric assessment based on MRI. Ratio of volumetric change between the first MRI and the scan immediately before chemotherapy was defined as shrinking rate (%). Period between disease onset and the first chemotherapy was 20 to 47 days. Diagnostic radiation dose was calculated in each case. Initial tumor volume ranged from 0.962 to 72.356 cubic centimeters (mean: 9.67). Diagnostic radiation dose: 52.2 to 910.1 mGy. Shrinking rate ranged from -57.8 to 85.4% (mean: 28.7). In only 7 regions (29.1%), shrinking rate was within 30%. Shrinking rate was significant positively influenced by diagnostic radiation dose (p<0.05) and negatively influenced by initial volume (p<0.05). But, it had no correlation with age, sex, histopathological parameters. This study shows that the volume of intracranial germ cell tumors is changing dynamically in many cases. Diagnostic exposure to low-dose radiation influences spontaneous regression in intracranial germinomas.