tbuckley/cabot-search huggingface dataset:
Prospective Study of Cancer Genetic Variants: Variation in Rate of Reclassification by Ancestry
Authors: Thomas P Slavin, Lily R Van Tongeren, Carolyn E Behrendt, Ilana Solomon, Christina Rybak, Bita Nehoray, Lili Kuzmich, Mariana Niell-Swiller, Kathleen R Blazer, Shu Tao, Kai Yang, Julie O Culver, Sharon Sand, Danielle Castillo, Josef Herzog, Stacy W Gray, Jeffrey N Weitzel
Journal: JNCI Journal of the National Cancer Institute (2018)

In germline genetic testing, variants from understudied ancestries have been disproportionately classified as being of uncertain significance. We hypothesized that the rate of variant reclassification likewise differs by ancestry. Nonbenign variants in actionable genes were collected from consenting subjects undergoing genetic testing at two Southern California sites from September 1996 through December 2016. Variant reclassifications were recorded as they were received, until February 2017 or reclassification to benign. Excluding duplicate variants (same ancestry, laboratory, classification), generalized linear models for the hereditary breast cancer genes (BRCA1/2) and other variants investigated whether rate of reclassification differed for seven categories of ancestry compared with non-Hispanic European. Models took into account laboratory, year, gene, sex, and current classification (handled as a time-dependent covariate) and were adjusted for multiple hypothesis testing. Among 1483 nonbenign variants, 693 (46.7%) involved BRCA1/2. Overall, 268 (18.1%) variants were reclassified at least once. Few (9.7%) reclassified variants underwent a net upgrade in pathogenicity. For BRCA1/2 variants, reclassification rates varied by ancestry and increased over time, more steeply for ancestries with lower initial rates (African, Ashkenazi, Chinese) than for ancestries whose initial rates were high (Middle Eastern) or similar to non-Hispanic European (non-Chinese Asian, Native American, Hispanic). In contrast, reclassification rates of non-BRCA1/2 variants did not vary over time but were elevated for most minority ancestries except non-Chinese Asian and Native American. For nonbenign variants in cancer-related genes, the rates at which reclassifications are issued vary by ancestry in ways that differ between BRCA1/2 and other genes.
Endoscopic retrograde cholangiopancreatography
Authors: Jong Moon, Hyun Choi, Yun Lee
Journal: Endoscopy (2014)

New technological developments in endoscopic retrograde cholangiopancreatography (ERCP) for diagnosis and treatment have been slow to progress. However, several informative study results were presented during the 2014 Digestive Disease Week (DDW; 3 - 6 May; Chicago, Illinois, USA) in specific ERCP areas, such as prevention of post-ERCP pancreatitis using nonsteroidal anti-inflammatory drugs and pancreatic duct stenting. Novel and interesting study results regarding preoperative stent selection for periampullary tumors, metal stents for hilar stricture or for prevention of duodenal reflux, and intraductal biliary tumor ablation using photodynamic therapy or radiofrequency ablation were discussed. Study results presented at the meeting regarding single-operator cholangioscopy using the SpyGlass system or direct peroral cholangioscopy have indicated the possibility of future development. Results using peroral pancreatoscopy and confocal laser endomicroscopy for biliary lesions, including strictures, were also presented.
Incidence of febrile neutropenia (FN) with pegfilgrastim (PF) on day of chemotherapy (D1) versus 24–72 hrs later (D2)
Authors: P. Kumar, A. M. Ingle, S. Miller, M. Woods, S. P. Thomas
Journal: Journal of Clinical Oncology (2009)

e20664 Background: Docetaxel, doxorubicin hydrochloride, and cyclophosphamide (TAC) is a commonly used adjuvant chemotherapy (C) regimen in patients (pts) with high risk breast cancer (BC). Pegfilgrastim (PF) is a long acting G-CSF known to decrease the risk of FN. It is typically given the day after C. Illinois CancerCare (ILCC) is a large oncology practice that provides cancer care to many communities in Illinois. For patients with limited access to medical care, in past PF has been given on same day as C. In this study we have compared the incidence of FN in pts who received PF on the same day as TAC (D1) versus those who received it 24–72 hrs after C (D2). Methods: All pts treated for BC at ILCC between 09/2004 and 08/2008, and received TAC and PF were deemed eligible. Logistic regression was used to analyze the association between incidence of FN and type of regimens. Results: Of the 56 eligible pts (55 females), mean age 52.9 yrs (range 27.8–84.8 yrs), 43 patients received PF on D1 and 13 pts received PF on D2. 7 of 43 pts that received PF on D1 developed FN as compared to 1 of 13 pts that received PF on D2. There was a 2.1 times greater probability of developing FN in pts that received PF on D1 versus the pts who received it on D2; 95% CI (0.28–15.6). We did not observe a statistical significance for the above association in univariate analyses or after adjusting for age, stage of disease and receptor status (p&gt;0.05). The lack of significance could be due to small patient population. Conclusions: The odds of developing FN in patients who received PF on the same day as TAC was 2.1 as compared to pts who received it on D2, this difference was statistically not significant. [Table: see text]
REBLEEDING RATE AND RELATED RISK FACTORS OF NON-STEROIDAL ANTI-INFLAMMATORY DRUG-INDUCED ENTEROPATHY
Authors: J Park, JO Kim, SR Jeon, HG Kim, TH Lee, JH Cho, BM Ko, JS Lee, MS Lee
Journal: Endoscopy (2018)

Limited evidence is available regarding rebleeding due to non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy. Previous studies have primarily analyzed endoscopic findings. Therefore, there is a need to evaluate the clinical implications for patients. The aim of this study was to evaluate the rebleeding rate and its related risk factors in patients with NSAID-induced enteropathy.
Duration of Adjuvant Chemotherapy for Stage III Colon Cancer
Authors: Axel Grothey, Alberto F. Sobrero, Anthony F. Shields, Takayuki Yoshino, James Paul, Julien Taieb, John Souglakos, Qian Shi, Rachel Kerr, Roberto Labianca, Jeffrey A. Meyerhardt, Dewi Vernerey, Takeharu Yamanaka, Ioannis Boukovinas, Jeffrey P. Meyers, Lindsay A. Renfro, Donna Niedzwiecki, Toshiaki Watanabe, Valter Torri, Mark Saunders, Daniel J. Sargent, Thierry Andre, Timothy Iveson
Journal: New England Journal of Medicine (2018)

Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures.
DEVELOPMENT AND VALIDATION OF A COLONOSCOPY SATISFACTION AND SAFETY QUESTIONNAIRE BASED ON PATIENT'S EXPERIENCE (CSSQP)
Authors: A Brotons, JJ Mira, J Lacueva, B Germán, MF García-Sepulcre, J Sola-Vera
Journal: Endoscopy (2018)

Colonoscopy services must ensure the implementation of quality assesment and improvement programs from patients' perspective. The aim of this study was to design and validate a specific questionnaire for patients undergoing colonoscopy within the colorectal cancer (CRC) program, the Colonoscopy Satisfaction and Safety Questionnaire based on Patient experience (CSSQP).
MESH REINFORCEMENT IN ANTIREFLUX SURGERY – ADVERSE EVENTS AND ENDOSCOPIC MANAGEMENT
Authors: P Costa-Moreira, E Rodrigues-Pinto, G Macedo
Journal: Endoscopy (2018)

A 86-year-old woman with a large paraesophageal hiatal hernia (PEHH) underwent laparoscopic cruroplasty with Nissen fundoplicature and placement of an expanded polytetrafluoroethylene dual mesh. She presented 24 months later with dysphagia for solids. Endoscopy revealed a stenosis at the gastroesophageal junction, submitted to a 6-month period of through-the-scope endoscopic balloon dilation. One month after last dilation, the patient presented with subacute onset of severe dysphagia. Endoscopy showed an esophageal mucosal discontinuity upstream from a stenosis, with the surgical mesh being apparent through the defect. A fully covered 80 mm long × 20 mm diameter self-expandable metal stent (Hanarostent M.I.Tech Co., Inc, Seoul, South Korea) was placed across the stricture with clinical improvement and hospital discharge two days later. The stent was removed 6 weeks later without adverse events (AEs), however, the surgical mesh was partially migrated and embedded in the esophageal lumen. A further CT excluded any other AEs. Due to worsening of dysphagia, a 4 cm-long fully covered diablo-shape stent (Hanarostent 26/16/26 mm) was placed two days later, with the patient reporting weight gain and resolution of dysphagia. Removal of the stent is not planned.
PERORAL ENDOSCOPIC MYOTOMY FOR THE TREATMENT OF ESOPHAGEAL MOTILITY DISORDERS: BASELINE CHARACTERISTICS AND PROCEDURAL OUTCOMES IN YOUNG AND ELDERLY PATIENTS
Authors: R Landi, P Familiari, F Mangiola, A Calì, F Borrelli De Andreis, V Bove, F D'Aversa, A Costantini, I Boskoski, A Tringali, V Perri, G Costamagna
Journal: Endoscopy (2018)

Peroral endoscopic myotomy (POEM) has been proven to be effective for treatment of achalasia. There are limited data on efficacy and safety of POEM in elderly patients. We therefore aimed to assess the role of POEM in patients aged ≥65 years.
A global transcriptional network connecting noncoding mutations to changes in tumor gene expression
Authors: Wei Zhang, Ana Bojorquez-Gomez, Daniel Ortiz Velez, Guorong Xu, Kyle S. Sanchez, John Paul Shen, Kevin Chen, Katherine Licon, Collin Melton, Katrina M. Olson, Michael Ku Yu, Justin K. Huang, Hannah Carter, Emma K. Farley, Michael Snyder, Stephanie I. Fraley, Jason F. Kreisberg, Trey Ideker
Journal: Nature Genetics (2018)
THE USE OF A NEW CORE NEEDLE IN THE ENDOSCOPIC ULTRASOUND ASSISTED TISSUE SAMPLING FOR PANCREATIC SOLID MASSES: A MULTICENTRE PROSPECTIVE STUDY
Authors: S Carrara, M Di Leo, L Bernardoni, D Rahal, G Donato, M Massidda, A Anderloni, SF Crinò, E Manfrin, M Ballarè, L Poliani, F Auriemma, A Fugazza, P Occhipinti, A Repici
Journal: Endoscopy (2018)

Endoscopic ultrasound-guided biopsy (EUS-biopsy) is safe and effective technique for obtaining samples from pancreatic masses. The aim of the present study was to evaluate the presence of a histological sample using 25G SharkCore Needles (Medtronic, Dublin, Ireland).
Endoscopic tumor diagnosis and treatment
Authors: Srinivas Gaddam, Steven Edmundowicz
Journal: Endoscopy (2013)

This year’s Digestive Disease Week (May 18 – 21, 2013, Orlando, Fla) presented new perspectives on endoscopic diagnosis and management of GI tumors. These abstracts can be broadly divided into tumors of the upper and lower GI tract and pancreatobiliary tumors.
Selection and Efficacy of Cytoreductive Agents in Patients with Mastocytosis Included in the Registry of the European Competence Network on Mastocytosis (ECNM)
Authors: Chiara Elena, Serena Merante, Virginia Valeria Ferretti, Lambertus Cm Span, Aleksandra Górska, Massimiliano Bonifacio, Cecelia Perkins, Olivier Hermine, Anja Illerhaus, Sabine Mueller, Roberta Parente, Mohamad Jawhar, Elena Fontana, Alexander Zink, Alex Kilbertus, Akif Selim Yavuz, Michael Doubek, Hans Hagglund, Jens P. Panse, Vito Sabato, Haifa Kathrin Al Ali, Elisabeth Aberer, Marie Anne Morren, Magdalena Lange, David Fuchs, Knut Brockow, Anna Belloni Fortina, Andreas Reiter, Massimo Triggiani, Nikolas von Bubnoff, Karin Hartmann, Jason Gotlib, Luigi Scaffidi, Marek Niedoszytko, Hanneke Kluin-Nelemans, Luca Malcovati, Wolfgang R. Sperr, Peter Valent
Journal: Blood (2017)
Genetic subtypes of large cell neuroendocrine carcinoma (LCNEC) to predict response to chemotherapy.
Authors: Jules Derks, Noémie Leblay, Robert Jan van Suylen, Erik Thunnissen, Michael den Bakker, Harry J.M. Groen, Egbert F. Smit, Ronald Damhuis, Esther van de Broek, Amélie Chabrier, Matthieu Foll, James McKay, Lynnette Fernandez-Cuesta, Ernst-Jan M. Speel, Anne-Marie C. Dingemans
Journal: Journal of Clinical Oncology (2017)

9061 Background: To treat LCNEC with non-small cell lung carcinoma type chemotherapy (NSCLC-ct, i.e. gemcitabine/taxanes or pemetrexed) or small cell lung carcinoma type (SCLC-ct, i.e. platinum-etoposide) is subject of debate. Molecular studies have identified two mutually exclusive subtypes in LCNEC, the co-mutated TP53 and RB1and the STK11/ KEAP1 (predominantly RB1 wildtype( wt )) group. We investigated if overall survival (OS) and progression free survival (PFS) correlates with targeted next-generation sequencing (TNGS) results in LCNEC treated with NSCLC-ct or SCLC-ct. Methods: For this population based retrospective cohort study all diagnoses of stage IV ct treated high grade neuroendocrine carcinomas (NEC, not being SCLC) were retrieved from the Netherlands Cancer Registry and Pathology Registry (PALGA) (2003-2012). Panel-consensus pathology revision of original tumor slides was performed on (N = 230) and TNGS for genes TP53, RB1, STK11 and KEAP1 analyzed with a multi-sample variant caller (Needlestack). Results: LCNEC was consensus diagnosed in 146/230 and 77 passed quality control for TNGS. Mean coverage was 2832x, a mutation( mt ) in TP53 was present in 87%, RB1 mt in 46%, STK11 mt in 13% and KEAP1 mt in 18% of sequenced LCNEC. RB1 was co-altered with TP53 in 94% of LCNEC; mutually exclusive to STK11 mt (100%) but not KEAP1 mt (57%). NSCLC-ct or SCLC-ct was specified in 92% of patients and RB1 wt LCNEC treated with NSCLC-ct (n = 22) showed a trend to better OS compared to SCLC-ct (n = 13) (8.5 months (95% confidence interval (CI): [6.3-10.6]) vs. 5.8 [5.5-6.1] months, p = 0.055). Due to reported resistance in NECs we analyzed NSCLC-ct without pemetrexed-ct; OS was significantly longer for NSCLC-ct (n = 15) compared to SCLC-ct (9.6 [7.7-11.6] vs. 5.8 [5.5-6.1] months, p = 0.026). PFS of RB1 wt NSCLC-ct treated patients was significantly longer than SCLC-ct (p = 0.044), without pemetrexed (p = 0.018). In patients with RB1 mt LCNEC OS/PFS was not significantly different for NSCLC-ct vs. SCLC-ct. Conclusions: In LCNEC with RB1 wt , NSCLC-ct correlates with a more favorable outcome compared to SCLC-ct. However, RB1 mt LCNEC treated with NSCLC-ct do similarly worse as SCLC-ct. Prospective studies should be initiated.
LOST TV ANTENNA DISCOVERED TOGETHER WITH A FORGOTTEN NAIL
Authors: M Galanopoulos, F Gkeros, E Tsoukali, A Tsigaridas, N Viazis, A Moss, E Archavlis, GJ Mantzaris
Journal: Endoscopy (2018)

Ingestion of foreign bodies is commonly encountered in clinical practice involving, mainly paediatric populations. Our aim is to report an unusual case of ingestion of two sizeable metal objects, in an asymptomatic adult prisoner.
Radiopaque nano and polymeric materials for atherosclerosis imaging, embolization and other catheterization procedures
Authors: Li Tian, Linfeng Lu, James Feng, Marites P. Melancon
Journal: Acta Pharmaceutica Sinica B (2018)

A review of radiopaque nano and polymeric materials for atherosclerosis imaging and catheterization procedures is presented in this paper. Cardiovascular diseases (CVDs) are the leading cause of death in the US with atherosclerosis as a significant contributor for mortality and morbidity. In this review paper, we discussed the physics of radiopacity and X-ray/CT, clinically used contrast agents, and the recent progress in the development of radiopaque imaging agents and devices for the diagnosis and treatment of CVDs. We focused on radiopaque imaging agents for atherosclerosis, radiopaque embolic agents and drug eluting beads, and other radiopaque medical devices related to catheterization procedures to treat CVDs. Common strategies of introducing radiopacity in the polymers, together with examples of their applications in imaging and medical devices, are also presented.
Neurosurgery: A Silk Cranial Fixation System for Neurosurgery (Adv. Healthcare Mater. 6/2018)
Authors: Keyin Liu, Zhifeng Shi, Shaoqing Zhang, Zhitao Zhou, Long Sun, Tao Xu, Yeshun Zhang, Guozheng Zhang, Xinxin Li, Liang Chen, Ying Mao, Tiger H. Tao
Journal: Advanced Healthcare Materials (2018)

In article number 1701359, Ying Mao, Tiger H. Tao, and co-workers report on the silk cranial fixation system. The system includes silk screws and strips to anchor the bone flap, which are fabricated from natural silk proteins obtained from cocoons of the Bombyx mori silkworm. The system is used to provide a protective shield to brain after neurosurgery.
Results of a phase I trial of KX2–391, a novel non-ATP competitive substrate-pocket directed SRC inhibitor, in patients with advanced malignancies
Authors: A. A. Adjei, R. B. Cohen, R. Kurzrock, G. S. Gordon, D. Hangauer, L. Dyster, G. Fetterly, S. Barrientes, D. S. Hong, A. Naing
Journal: Journal of Clinical Oncology (2009)

3511 Background: Src kinase is central to the proliferation, apoptosis and metastasis of tumor cells. KX2–391 is a synthetic, orally bioavailable small molecule Src tyrosine kinase signaling inhibitor. KX2–391 is distinct from all other known Src kinase inhibitors in targeting the peptide substrate-binding site and not the ATP-binding site. KX2–391 is the first peptide site targeted tyrosine kinase inhibitor to enter clinical trials. KX2–391 has a much wider spectrum of solid tumor activity in vitro, and is more potent in mouse xenografts, as compared to other multikinase Src/Abl inhibitors. Methods: This multi-center Phase 1 trial utilized the standard 3+3 design to determine the Maximum Tolerated Dose (MTD), safety, and pharmacokinetics (PK) of KX2–391 in pts with refractory solid tumors. Results: To date, 32 pts (12 m 20 f, median age 59 (range 31–78)) have been enrolled in 7 dose cohorts. Dose limiting toxicities (DLTs), which were all reversible within 7 days, occurred in 4 pts and included elevated ALT and AST, neutropenia, and fatigue. 22 pts experienced no Grade 3 or 4 adverse events. Other Grade 1/2 adverse events include: hypokalemia, anemia, elevated AST, fatigue, dyspnea, fever, vomiting, constipation, hematuria, and lymphopenia. The MTD is 40 mg BID on a 3 out of 4 weeks dosing schedule. 7 pts had prolonged stable disease for 4 months or longer including 2 pts with papillary thyroid carcinoma, 2 with carcinoid, and 1 each with prostate, pancreas, and head and neck cancer. Both the prostate and pancreatic cancer pts had dramatic decreases in their biomarkers (PSA went from 205 ng/ml to 39 ng/ml, and CA19–9 went from 38,838 U/ml to 267 U/ml, respectively). The PK profile demonstrated dose-proportionality, a half-life of 4.5 hrs and a Tmax of 1 hr with no evidence of accumulation with multiple doses. Conclusions: KX2–391 has a favorable PK profile, is well-tolerated, demonstrates preliminary evidence of biologic activity and should be further evaluated in Phase II trials. [Table: see text] [Table: see text]
Factors Influencing Men's Choice of and Adherence to Active Surveillance for Low-risk Prostate Cancer: A Mixed-method Systematic Review
Authors: Netty Kinsella, Pär Stattin, Declan Cahill, Christian Brown, Anna Bill-Axelson, Ola Bratt, Sigrid Carlsson, Mieke Van Hemelrijck
Journal: European Urology (2018)
EUS guided Rendezvous Technique for Biliary Access after Failed Cannulation
Authors: Iwashita Takuji, JG Lee, Shinoura Susumu, V Raman Muthusamy, KJ Chang
Journal: Endoscopy (2011)

Introduction: Selective cannulation fails in 3% of endoscopic retrograde cholangiography (ERC). EUS guided rendezvous (EUS-RV) can salvage failed cannulation. Aims: To determine the safety and efficacy of EUS-RV in a consecutive series of patients undergoing ERC.
Development and Evaluation of an Optimal Human Single-Chain Variable Fragment-Derived BCMA-Targeted CAR T Cell Vector
Authors: Eric L. Smith, Mette Staehr, Reed Masakayan, Ishan J. Tatake, Terence J. Purdon, Xiuyan Wang, Pei Wang, Hong Liu, Yiyang Xu, Sarah C. Garrett-Thomson, Steven C. Almo, Isabelle Riviere, Cheng Liu, Renier J. Brentjens
Journal: Molecular Therapy (2018)

B cell maturation antigen (BCMA) has recently been identified as an important multiple myeloma (MM)-specific target for chimeric antigen receptor (CAR) T cell therapy. In CAR T cell therapy targeting CD19 for lymphoma, host immune anti-murine CAR responses limited the efficacy of repeat dosing and possibly long-term persistence. This clinically relevant concern can be addressed by generating a CAR incorporating a human single-chain variable fragment (scFv). We screened a human B cell-derived scFv phage display library and identified a panel of BCMA-specific clones from which human CARs were engineered. Despite a narrow range of affinity for BCMA, dramatic differences in CAR T cell expansion were observed between unique scFvs in a repeat antigen stimulation assay. These results were confirmed by screening in a MM xenograft model, where only the top preforming CARs from the repeat antigen stimulation assay eradicated disease and prolonged survival. The results of this screening identified a highly effective CAR T cell therapy with properties, including rapid in vivo expansion (>10,000-fold, day 6), eradication of large tumor burden, and durable protection to tumor re-challenge. We generated a bicistronic construct including a second-generation CAR and a truncated-epithelial growth factor receptor marker. CAR T cell vectors stemming from this work are under clinical investigation.
IRON DEFICIENCY ANEMIA – DEVELOPMENT OF A PREDICITIVE MODEL FOR GASTROINTESTINAL MALIGNANCY (MINHO MODEL)
Authors: S Xavier, J Firmino-Machado, J Magalhães, J Cotter
Journal: Endoscopy (2018)

Iron deficiency anemia (IDA) may be the only sign of gastrointestinal (GI) malignancy. Identification of predictive factors of GI malignancy could help the physician to establish patients’ priority to endoscopic assessment, contributing to an earlier diagnosis.
Dynamic telecytopathology is comparable to rapid onsite evaluation (ROSE) of endoscopic ultrasound fine needle aspirates: results of a prospective pilot study
Authors: J Buxbaum
Journal: Endoscopy (2011)

Background: Endoscopic Ultrasound (EUS) with fine needle aspiration (FNA) is a highly accurate method to diagnose lesions in even the most remote aspects of the thorax and peritoneum. Nonetheless, it is invasive and requires continuous patient sedation, thus real time assessment of specimen quality is imperative. ROSE has been demonstrated to correlate highly with final cytologic interpretations and improves the diagnostic yield of EUS-FNA However, due to limited time and financial resources its availability is variable across centers. The objective of this prospective study was to evaluate whether remote telecytopathology can substitute for ROSE.
Traitement des fistules oesophagiennes après oesophagectomie par prothèse couverte auto-expansive
Authors: L Heyries, X Lagrange, A Guillin-Poujol, JP Bernard, C Doddoli, P Thomas, J Sahel
Journal: Endoscopy (2009)

But: Etude rétrospective des résultats à long terme de l'intubation oesophagienne par prothèse métallique couverte pour le traitement des fistules oesophagiennes post opératoires.
ACCURACY OF FORCEPS BIOPSY OF GASTRIC EPITHELIAL NEOPLASIA BEFORE ENDOSCOPIC SUBMUCOSAL DISSECTION
Authors: M Gomez, M Rullan, A Elosua, D Oyon, S Lopez, J Carrascosa, JF Juanmartiñena, L Uribarri, E Albeniz, JJ Vila
Journal: Endoscopy (2018)

Previous studies from eastern countries found that approximately 25% to 35% of the histological diagnoses based on forceps biopsies for gastric dysplastic lesions change following endoscopic resection. The aim of this study was to compare the diagnostic accuracy between conventional forceps biopsy and endoscopic submucosal dissection (ESD) in a western country.