tbuckley/cabot-search huggingface dataset:
Vertebral Myeloma Mimicking Prostatic Carcinoma Metastasis in 68Ga-PSMA PET/CT
Authors: Esben Hoej Merrild, Steen Baerentzen, Kirsten Bouchelouche, Simon Buus
Journal: Clinical Nuclear Medicine (2017)

Ga-PSMA PET/CT was performed in a 75-year-old man with newly diagnosed prostate cancer because of an equivocal lesion in the spine both on Tc-bone-SPECT/CT and MRI. Because of increased PSMA activity on PET/CT, the bone lesion was interpreted as metastasis from prostate cancer. Later, the patient was diagnosed as having monoclonal gammopathy of unknown significance. A biopsy was performed, and histological examination revealed multiple myeloma with PSMA expression in the neovessels but no metastatic prostate cancer cells. The patient was downstaged, and the treatment was changed accordingly. This case illustrates the importance of biopsies from PSMA PET-positive lesions.
Does a lung cancer screening programme promote smoking cessation?
Authors: Filippo Lococo, Giuseppe Cardillo, Giulia Veronesi
Journal: Thorax (2017)

Lung cancer is a preventable form of cancer with approximately 90% of cases attributable to cumulative tobacco exposure.1 Smoking cessation and early detection of lung cancer remain critical goals for lung cancer prevention and control. Indeed, the health benefits of smoking cessation reach well beyond reducing the risk of lung cancer,2 resulting in an overall reduction of tobacco-related mortality. Unfortunately, smoking cessation delivery and patient adherence is still a major challenge.

While there is a body of evidence supporting smoking cessation (primary prevention) and early detection of lung cancer (secondary prevention) to decrease lung cancer mortality, data on the effectiveness and interaction between smoking cessation and lung cancer screening are still sparse and inconsistent.3–6 The administration of a rigorous smoking cessation intervention (based on the combination of counselling and drug treatment) to a lung cancer screening population may lead to high smoking cessation rates (up to 30%3).

Published in Thorax , the UK Lung Cancer Screening (UKLS) trial group report the effect of low-dose CT screening on smoking cessation.7 The UKLS trial assessed the feasibility, cost-effectiveness and psychosocial impact of lung cancer screening using a single low-dose CT screen versus no screening in a UK high-risk population. The authors have investigated the behavioural effect of trial participation on smoking cessation in …
AB1014 Safety of outpatient percutaneous native renal biopsy in patients with systemic autoimmune diseases: results from a monocentric cohort
Authors: D Roccatello, S Sciascia, D Rossi, C Naretto, M Bazzan, L Solfietti, M Radin, S Baldovino, E Menegatti
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Renal involvement is common in patients with systemic autoimmune conditions, mainly systemic lupus erythematosus (SLE) and vasculitis, including cryoglobulinemia. Despite the advances in percutaneous kidney biopsy (PKB) techniques and overall improved safety of the procedure, clinically significant bleeding complications do occur. <h3>Objectives</h3> to investigate the safety of performing percutaneous native kidney biopsy (PKB) as an outpatient procedure (implying an observation period of 6 hrs) compared to the traditional inpatient policy in patients with systemic autoimmune conditions. <h3>Methods</h3> Group I, in whom PKB was performed in the outpatient department (2012–2016) and followed by 6 hours9 observation period and then by regular outpatient visits and group II, in whom PKB was performed and followed by at least 1-day hospital admission. Group II included retrospectively retrieved patients who underwent PKB in our Institution between January 2000 and November 2012 as in patient procedure. All biopsies were performed by a single nephrologist following a structured protocol. <h3>Results</h3> A total of 81 biopsies (group I and group II) were included in this study, 44 (54%) of patients were female and the mean age was 49.9±17.6 years. Twenty-six per cent of biopsies were performed for the diagnostic workup of nephrotic range proteinuria, 21% for rapidly progressive renal insufficiency, and the remaining 53% for non-nephrotic proteinuria and/or hematuria. No patient suffered for a major complication and only 3 (3.7%) patients (one with cryoglobulinemic vasculitis and 2 with ANCA associated vasculits) developed a minor complication, including gross hematuria in one case and sub-capsular perinephric hematoma on sonography not requiring intervention in 2 patients <h3>Conclusions</h3> The lack of major complications and the very limited rate of minor bleeding support that outpatient biopsy could be a valuable, safe, and perhaps cost-effective method of obtaining diagnostic renal tissue in the majority of patients with systemic autoimmune diseases. <h3>Disclosure of Interest</h3> None declared
A Novel Functional Splice Variant of <i>AKT3</i> Defined by Analysis of Alternative Splice Expression in HPV-Positive Oropharyngeal Cancers
Authors: Theresa Guo, Akihiro Sakai, Bahman Afsari, Michael Considine, Ludmila Danilova, Alexander V. Favorov, Srinivasan Yegnasubramanian, Dylan Z. Kelley, Emily Flam, Patrick K. Ha, Zubair Khan, Sarah J. Wheelan, J. Silvio Gutkind, Elana J. Fertig, Daria A. Gaykalova, Joseph Califano
Journal: Cancer Research (2017)

The incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) has increased more than 200% in the past 20 years. Recent genetic sequencing efforts have elucidated relevant genes in head and neck cancer, but HPV-related tumors have consistently shown few DNA mutations. In this study, we sought to analyze alternative splicing events (ASE) that could alter gene function independent of mutations. To identify ASE unique to HPV-related tumors, RNA sequencing was performed on 46 HPV-positive OPSCC and 25 normal tissue samples. A novel algorithm using outlier statistics on RNA-sequencing junction expression identified 109 splicing events, which were confirmed in a validation set from The Cancer Genome Atlas. Because the most common type of splicing event identified was an alternative start site (39%), MBD-seq genome-wide CpG methylation data were analyzed for methylation alterations at promoter regions. ASE in six genes showed significant negative correlation between promoter methylation and expression of an alternative transcriptional start site, including AKT3 The novel AKT3 transcriptional variant and methylation changes were confirmed using qRT-PCR and qMSP methods. In vitro silencing of the novel AKT3 variant resulted in significant growth inhibition of multiple head and neck cell lines, an effect not observed with wild-type AKT3 knockdown. Analysis of ASE in HPV-related OPSCC identified multiple alterations likely involved in carcinogenesis, including a novel, functionally active transcriptional variant of AKT3 Our data indicate that ASEs represent a significant mechanism of oncogenesis with untapped potential for understanding complex genetic changes that result in the development of cancer. Cancer Res; 77(19); 5248-58. ©2017 AACR.
TUSC2 Enhances Sensitivity to Anti-PD1 in Kras Mutant Syngeneic Mouse Lung Cancer Through NK Cells
Authors: I.M. Meraz, M. Majidi, X. Cao, H. Lin, L. Li, Jing Wang, V. Baladandayuthapani, D. Rice, B. Sepesi, L. Ji, J.A. Roth
Journal: Journal of Thoracic Oncology (2017)
Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study
Authors: Michael J Overman, Ray McDermott, Joseph L Leach, Sara Lonardi, Heinz-Josef Lenz, Michael A Morse, Jayesh Desai, Andrew Hill, Michael Axelson, Rebecca A Moss, Monica V Goldberg, Z Alexander Cao, Jean-Marie Ledeine, Gregory A Maglinte, Scott Kopetz, Thierry André
Journal: The Lancet Oncology (2017)
Effect of lanreotide depot (LAN) on 5-hydroxyindoleacetic acid (5HIAA) and chromogranin A (CgA) in gastroenteropancreatic neuroendocrine (GEP NET) tumors: Correlation with tumor response and progression-free survival (PFS) from the phase III CLARINET study.
Authors: Alexandria T. Phan, Edward M. Wolin, Nilani Liyanage, Beloo Mirakhur, Susan W. Pitman Lowenthal, Aaron Vinik, George A. Fisher, Marianne Pavel
Journal: Journal of Clinical Oncology (2017)

4095 Background: 5HIAA or CgA are biomarkers in some GEP NETs. We present posthoc analyses using prospectively collected urinary 5HIAA and serum CgA data from CLARINET. Methods: Adults with moderately or well differentiated, nonfunctioning (no symptoms of carcinoid syndrome), locally advanced or metastatic GEP NETs were randomized to LAN 120mg or placebo (PBO) every 4 weeks (wks) for 96 wks. Tumor response evaluated centrally (RECIST 1.0) and PFS were assessed by treatment. Biochemical response was defined as baseline &gt; upper limit of normal (ULN, 41.6µmol/d 5HIAA; 98.1µg/L CgA) and ≥50% decrease from baseline to ≤ULN value on study. CgA analyses excluded gastrinoma patients (pts). Results: 48% (82/171) (45LAN; 37PBO) and 66% (129/195) (65LAN, 64PBO) of pts had &gt; ULN baseline 5HIAA and CgA. In those pts with no radiologic progression, significantly greater reductions in 5HIAA (Table) and CgA were observed in LAN vs PBO pts at all assessments (all P&lt; 0.05). PFS was significantly prolonged in LAN 5HIAA responders vs nonresponders (median not reached vs 22.1 months, P= 0.0076) but was not significantly different in PBO 5HIAA responders vs nonresponders. There were no significant differences in PFS by CgA response (responders vs nonresponders) in either LAN or PBO pts. Conclusions: These data suggest that serotonin is secreted by nonfunctioning tumors, but does not reach the threshold required for clinical carcinoid symptoms. Monitoring 5HIAA and CgA may be useful during LAN treatment of nonfunctional GEP NETs. Clinical trial information: NCT00353496. [Table: see text]
Hyperactive Non-Canonical TGF-β Pathway Signaling in Fanconi Anemia Bone Marrow Stromal Cells Contributes to Growth Suppression
Authors: Kevin O'Connor, Sofia Vidal-Cardenas, Haojian Zhang, Alfredo Rodriguez, Lisa Moreau, Chunyu Yang, Michael W Epperly, Markus Grompe, Akiko Shimamura, Joel S. Greenberger, Kalindi Parmar, Alan D D'Andrea
Journal: Blood (2016)
Advances in the diagnosis of pneumonia in children
Authors: Heather J Zar, Savvas Andronikou, Mark P Nicol
Journal: BMJ (2017)

Pneumonia remains a major cause of childhood mortality and morbidity globally. Accurate diagnosis and attribution of the causes of pneumonia are important for measuring the burden of disease, implementing appropriate preventive or treatment strategies, and developing more effective interventions. This review summarizes recent diagnostic advances in radiological techniques, specimen collection, and laboratory methods. Although chest ultrasound and chest magnetic resonance imaging are promising modalities for radiological diagnosis, their role in clinical management and their impact on outcomes need further study. Rapid, highly sensitive, multiplex laboratory tests performed on upper respiratory tract samples or induced sputum can detect nucleic acid from potential pathogens in most children with pneumonia. However, it may be difficult to attribute causality because it is often impossible to distinguish between organisms colonizing or infecting the upper respiratory tract and those causing pneumonia. Currently available host biomarkers lack accuracy for distinguishing bacterial or mixed bacterial-viral infections from viral infections. New biomarkers derived from host transcriptional profile analysis may be more accurate but require validation. Prospective studies with appropriate control populations, including studies of clinical impact, are needed to improve our understanding of the role of tests. Although progress has been made in radiological techniques and laboratory testing, current methods for diagnosing and attributing the causes of pneumonia are suboptimal.
Epigenetic Drug Treatment Globally Induces Cryptic Transcription Start Sites Encoded in Long Terminal Repeats
Authors: Michael Daskalakis, David Brocks, Christopher Schmidt, Daofeng Li, Jing Li, Hyo S. Jang, Bo Zhang, Daniel B Lipka, Johanna Schott, Holger Bierhoff, Yassen Assenov, Monika Helf, Alzbeta Ressnerova, Anders Lindroth, Simon Haas, Marieke A. G. Essers, Charles D. Imbusch, Benedikt Brors, Ina Oehme, Olaf Witt, Michael Lübbert, Georg Stoecklin, Clarissa Gerhäuser, Christopher C Oakes, Ting Wang, Christoph Plass
Journal: Blood (2016)
Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome Combined With Adrenocortical Carcinoma on 18F-FDG PET/CT
Authors: Xiuyu Guo, Haojun Chen, Hao Fu, Hua Wu
Journal: Clinical Nuclear Medicine (2017)

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is a recognized distinct phenotypic variant of multiple cutaneous and uterine leiomyomatosis. The present case reports an extremely rare case of HLRCC syndrome combined with adrenocortical carcinoma. The case suggests that HLRCC should be considered in any young patient with bulky uterine leiomyomas and renal cell cancer, and 18F-FDG PET/CT can help detect unexpected additional primary malignancy in a patient with known cancer.
Prognostic relevance of genetic alterations in diffuse lower-grade gliomas
Authors: Kosuke Aoki, Hideo Nakamura, Hiromichi Suzuki, Keitaro Matsuo, Keisuke Kataoka, Teppei Shimamura, Kazuya Motomura, Fumiharu Ohka, Satoshi Shiina, Takashi Yamamoto, Yasunobu Nagata, Tetsuichi Yoshizato, Masahiro Mizoguchi, Tatsuya Abe, Yasutomo Momii, Yoshihiro Muragaki, Reiko Watanabe, Ichiro Ito, Masashi Sanada, Hironori Yajima, Naoya Morita, Ichiro Takeuchi, Satoru Miyano, Toshihiko Wakabayashi, Seishi Ogawa, Atsushi Natsume
Journal: Neuro-Oncology (2017)

Diffuse lower-grade gliomas (LGGs) are genetically classified into 3 distinct subtypes based on isocitrate dehydrogenase (IDH) mutation status and codeletion of chromosome 1p and 19q (1p/19q). However, the subtype-specific effects of additional genetic lesions on survival are largely unknown.Using Cox proportional hazards regression modeling, we investigated the subtype-specific effects of genetic alterations and clinicopathological factors on survival in each LGG subtype, in a Japanese cohort of LGG cases fully genotyped for driver mutations and copy number variations associated with LGGs (n = 308). The results were validated using a dataset from 414 LGG cases available from The Cancer Genome Atlas (TCGA).In Oligodendroglioma, IDH-mutant and 1p/19q codeleted, NOTCH1 mutations (P = 0.0041) and incomplete resection (P = 0.0019) were significantly associated with shorter survival. In Astrocytoma, IDH-mutant, PIK3R1 mutations (P = 0.0014) and altered retinoblastoma pathway genes (RB1, CDKN2A, and CDK4) (P = 0.013) were independent predictors of poor survival. In IDH-wildtype LGGs, co-occurrence of 7p gain, 10q loss, mutation in the TERT promoter (P = 0.024), and grade III histology (P < 0.0001) independently predicted poor survival. IDH-wildtype LGGs without any of these factors were diagnosed at a younger age (P = 0.042), and were less likely to have genetic lesions characteristic of glioblastoma, in comparison with other IDH-wildtype LGGs, suggesting that they likely represented biologically different subtypes. These results were largely confirmed in the cohort of TCGA.Subtype-specific genetic lesions can be used to stratify patients within each LGG subtype. enabling better prognostication and management.
Delays in breast cancer presentation and diagnosis in Nigeria.
Authors: Elima E. Jedy-Agba, Isabel dos-Santos-Silva, Oluwole Olaomi, Monday Yilkudi, Emmanuel Ezeome, Idris Sa'ad, Elijah Miner, Ikechukwu Anosike, Clement Adebamowo, Valerie McCormack
Journal: Journal of Clinical Oncology (2016)

e13092 Background: Breast cancer (BC) is the most common cancer among Nigerian women. In this study we investigated delays in BC presentation and their determinants. Methods: This is an on-going multi-centre case-control study at six hospitals in Nigeria (five in Abuja, and one in Enugu). From Jan 2014, we enrolled eligible women aged > 18years who presented with breast symptoms for suspected BC. We collected information regarding women’s experiences with their breast problem, including dates of initial symptoms and visits to all providers and factors that might have contributed to delays in presentation and diagnosis. Results: A total of 403 patients have been recruited so far: 206 cases of confirmed BC (mean age: 44.8 (SD = 12.1) years), and 197 with benign breast disease (BBD) (39.0 (9.6) years). Stage at diagnosis was known for 90% of BC patients, with ~50% having been diagnosed at an early stage (2.6% and 52.7% in stages I and II, respectively versus 27% and 17.7 in stages III and IV, repectively). The median (IQR) number of providers (including traditional healers) visited by a woman prior to diagnostic confirmation was 2 (1-2). The first provider was a public hospital for 58% of the participants, a private hospital/GP for 34.7% and an unorthodox provider for 7.3%. The median (IQR) time from first notice of symptoms to contact with any provider was 3 (0.7-7.1)and 1.3 (0.2-7.0) months, respectively, for BC and BBD patients. Main reasons given for delaying visit to the first provider were conviction that a breast lump was not a serious problem (59.7%), fear of diagnosis/treatment (10.8%), and financial constraints (8.6%). The median time (IQR) from first visit to a health facility to diagnosis was 4.0 (2.0-9.0) and 3 (1.0-6.5) months, respectively, for BC and BBD. Main reasons given for delay between presentation at a health facility and diagnostic confirmation were delayed test results (27.4%), being initially told by a doctor that it was not a serious problem (21.4%), and doctors’ strike (12%). Conclusions: Both patient and health system factors contributed to delayed presentation. Multi-regression models will be used to identify the main determinants of these delays and their associations with BC stage at presentation – the findings will be presented and discussed.
First-Trimester Urinary Bisphenol A Concentration in Relation to Anogenital Distance, an Androgen-Sensitive Measure of Reproductive Development, in Infant Girls
Authors: Emily S. Barrett, Sheela Sathyanarayana, Omar Mbowe, Sally W. Thurston, J. Bruce Redmon, Ruby H.N. Nguyen, Shanna H. Swan
Journal: Environmental Health Perspectives (2017)

Introduction: Evidence from animal models suggests that prenatal exposure to bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, is associated with adverse reproductive outcomes in females. Exposure during early gestation, a critical period for reproductive development, is of particular concern. Anogenital distance (AGD) is a sensitive biomarker of the fetal hormonal milieu and a measure of reproductive toxicity in animal models. In some studies, the daughters of BPA-exposed dams have shorter AGD than controls. Here, we investigate this relationship in humans. Methods: BPA was assayed in first-trimester urine samples from 385 participants who delivered infant girls in a multicenter pregnancy cohort study. After birth, daughters underwent exams that included two measures of AGD (AGD-AC: distance from center of anus to clitoris; AGD-AF: distance from center of anus to fourchette). We fit linear regression models to examine the association between specific gravity–adjusted (SPG-adj) maternal BPA concentrations and infant AGD, adjusting for covariates. Results: BPA was detectable in 94% of women. In covariate-adjusted models fit on 381 eligible subjects, the natural logarithm of SpG-adj maternal BPA concentration was inversely associated with infant AGD-AC [β=−0.56, 95% confidence interval (CI): −0.97, −0.15]. We observed no association between maternal BPA and infant AGD-AF. Conclusion: BPA may have toxic effects on the female reproductive system in humans, as it does in animal models. Higher first-trimester BPA exposure was associated with significantly shorter AGD in daughters, suggesting that BPA may alter the hormonal environment of the female fetus. https://doi.org/10.1289/EHP875
A phase 3 randomized double-blind trial of maintenance with niraparib versus placebo in patients with platinum-sensitive ovarian cancer (ENGOT-OV16/NOVA trial).
Authors: Ursula Matulonis, Sven Mahner, Robert Michael Wenham, Jonathan A. Ledermann, Bradley J. Monk, Jose Maria Del Campo, Jonathan S. Berek, Ignace Vergote, Michel Fabbro, Dionyssios Katsaros, Christian Marth, Domenica Lorusso, Jorn Herrstedt, Shefali Agarwal, Robert E. Martell, Mansoor Raza Mirza
Journal: Journal of Clinical Oncology (2014)

TPS5625 Background: Niraparib is a potent, oral poly(ADP-ribose)polymerase (PARP)1/2 inhibitor with efficacy in both germline BRCA mutation (gBRCAmut) ovarian cancer (OvCa) and BRCA negative (nongBRCAmut) high grade serous OvCa (HGSC). Ph I data established a RP2D of 300 mg with anti-OvCa activity and is well-tolerated. Methods: The ENGOT-OV16/NOVA study is a double-blind, 2:1 randomized, placebo controlled international ph III study of oral niraparib versus placebo in patients (pts) with platinum (plat) sensitive recurrent OvCa. Primary objective is to evaluate efficacy of niraparib as maintenance therapy in pts who have plat sensitive OvCa as assessed by the prolongation of progression free survival (PFS). PFS will be independently evaluated in a cohort of gBRCAmut pts and in pts who have HGSC histology and are nongBRCAmut. Secondary objectives are: (1) bridge the centralized BRCA mutation test method to the candidate companion diagnostic test, if needed; (2) evaluate add'l measures of clinical benefit including pt reported outcomes, PFS2, chemotherapy free interval, overall survival; (3) evaluate the safety/tolerability of niraparib vs placebo; (4) evaluate QTc in a subset of niraparib-treated OvCa pts. A recent food effect sub study in 15 pts demonstrated no effect of a high fat meal on the PK's of a single 300 mg dose of niraparib in OvCa pts. Main study eligibility includes: histologically confirmed OvCa, fallopian tube or peritoneal cancer, HGSC histology or known gBRCAmut, plat sensitive recurrence, completion of at least 2 previous courses of plat-containing therapy and sensitivity to both via radiographic imaging, normal or CA125 decrease by 90% after last plat, agreement by pt to undergo gBRCA status prior to randomization, availability of FFPE archival tumor, ECOG PS 0-1, normal organ function, and can take PO. The main study is sized to address PFS endpoint w/ an accrual goal of 360 pts. As of 04 February 2014, 37 pts have been enrolled and randomized in the study. The trial will be open at >100 sites in 15 countries in collaboration with ENGOT (NSGO, AGO, NCRI, GEICO, BGOG, GINECO, MaNGO, AGO Austria, MITO). Clinical trial information: NCT01847274.