tbuckley/cabot-search huggingface dataset:
The age specific genomic landscape of cancer.
Authors: Caitlin F. Connelly, Eric Allan Severson, Christopher Hanyoung Lieu, Joshua E. Meyer, Phil Stephens, Garrett Michael Frampton
Journal: Journal of Clinical Oncology (2017)

1568 Background: The frequency of genomic alterations in cancer is known to differ based on a patient’s age. Many studies have characterized the genomic characteristics of pediatric cancers; however, less is known about how the genomic landscape of mutations changes with age in adult patients. Accurately characterizing these differences will help guide personalized treatment strategies and illuminate differences in the genetic etiology of cancer at different ages of onset. Methods: Comprehensive genomic profiling was performed on &gt; 100,000 patients in the course of routine care for patients with predominantly relapsed, refractory or metastatic cancer. For 117 types of cancer with ≥ 100 cases, logistic regression was used to identify genomic features with statistically significant dependence on patient age. Results: Many known associations with age were identified, including increased prevalence of BRCA1/2 mutations in younger breast and ovarian cancer patients and increased prevalence of mismatch repair mutations in younger colorectal and endometrial adenocarcinoma patients. In lung adenocarcinoma, we identified 19 genes for which alteration prevalence was significantly associated with patient age. The genes ALK, ROS1, and RET were more commonly altered in younger patients, KRAS and MET were altered more frequently in older patients, and TP53 was most frequently altered at intermediate ages (40-60). Interestingly, a set of genes that have previously been associated with clonal hematopoiesis (CH) were found to be more frequently detected in older patients across a wide variety of cancer types. Based on the statistical power provided by this large cohort, several novel age based differences in gene alteration rates across multiple tumor types were detected and will be presented. Conclusions: Clear differences in genomics based on patient age were observed. This methodology can be used to identify novel associations between germline alterations and cancer types and somatic alterations that occur predominantly in young or elderly patients. These results also highlight the importance of accurately identifying and properly reporting somatic CH mutations during tumor genomic profiling.
Intraperitoneal chemotherapy for pancreatic cancer with peritoneal metastases: A single center retrospective analysis of 25 patients
Authors: Y. Tsuji, T. Takayama, N. Okamura, J. Sugiyama, S. Oiwa, M. Yoshida, Y. Okagawa, M. Hirayama, D. Sato, Y. Suzuki
Journal: Annals of Oncology (2018)

Introduction: Unresectable pancreatic cancer is one of the unfavorable prognosis cancers with merely one year of median overall survival (OS). Furthermore, the prognosis becomes even worse with peritoneal metastases due to reduced delivery capacity of anti-cancer drugs and lots of associated complications. Recently, the efficacy and safety data of intraperitoneal paclitaxel (ip PTX) in combination with systemic chemotherapy for gastric cancer with peritoneal metastases has been published by Ishigami at the ASCO 2016. We have participated in this intraperitoneal chemotherapy study projects and here we applied this strategy to pancreatic cancer with peritoneal metastases. Methods: Data from 25 patients with pancreatic cancer with peritoneal metastases who underwent intraperitoneal chemotherapy from August 2013 to January 2018 at our hospital were retrospectively analyzed. Results: Of the 25 patients, 8 were chemotherapy-naïve, and the remaining 17 had been adopted after prior non-intraperitoneal chemotherapy. 9 patients had undergone primary tumor resection before peritoneal recurrence. The intraperitoneal regimens were assigned mainly according to the prior treatment: ip PTX plus S-1/PTX was the most frequent (8 cases), followed by ip PTX plus FOLFIRINOX (7 cases), ip PTX plus gemcitabine (6 cases), and the rest. The median progression free survival (PFS) for all 25 patients was 6.1 months, and the median OS was 17.3 months. The median PFS and OS for the chemotherapy-naïve group were 8.6 and 17.3 months and for the prior-chemotherapy group were 3.1 and 11.9 months, respectively. The median PFS and OS for 11 patients without non-excision factors other than peritoneal metastases were 11.5 and 18.4 months. A point of extreme interest is that 5 of 11 patients achieved conversion surgery after confirmed complete disappearance of peritoneal metastases. Adverse events of grade 3 or 4 were observed: leukopenia at 40%, neutropenia 64% and anemia 24%, which we attributed to the systemic treatments. 2 cases of localized infection of peritoneal port were observed specific to intraperitoneal therapy. All treatments were well tolerable and there were no treatment-related deaths. Conclusion: This suggests, the combination of ip PTX with systemic chemotherapy for pancreatic cancer with peritoneal metastases provides survival benefit superior to conventional chemotherapy. We now only need to confirm these very promising results by a multicenter trial, and as soon as possible.
Recognition of Recurrent Protein Expression Patterns in Pediatric Acute Myeloid Leukemia Suggests New Therapeutic Targets
Authors: Fieke W Hoff, Chenyue W Hu, Yihua Qiu, Suk-Young Yoo, Amina Qutub, Eveline S. de Bont, Terzah M. Horton, Steven M. Kornblau
Journal: Blood (2016)
Assessing the breast cancer survivorship needs among the uninsured and underinsured.
Authors: Cecilia Yachuan Cai, Ling-Chen Chien, Myrna Katalina Serna, Stephanie Rico, Jennifer Arney, Polly Ann Niravath
Journal: Journal of Clinical Oncology (2016)

e21577 Background: With almost 12 million cancer survivors in the U.S., the Institute of Medicine (IOM) recommends provision of a treatment summary and survivorship care plan (TSSCP) to all cancer survivors. However, there has been limited research on the specific survivorship needs of ethnic minorities. Our study explores the needs of underserved breast cancer survivors in a publicly funded county health care system. Methods: We conducted focus group interviews with underserved breast cancer survivors. Each focus group was led by two facilitators who asked a fixed set of questions that focused on four domains: 1) challenges and side effects of therapy, 2) coping mechanisms, 3) knowledge deficits in the survivorship process, and 4) post-survivorship concerns. Interview recordings were transcribed and analyzed using techniques adapted from grounded theory and content analysis using a qualitative analysis software program. Results: The study conducted six focus groups with a total of seventeen breast cancer survivors, composed of African American, Hispanic, and Caucasian patients. Within the domain of challenges and side effects of therapy, concerns included femininity, body appearance after surgery, and intimacy. When asked about coping mechanisms, the majority of patients primarily relied on spirituality and support from family and church. The theme of spirituality was particularly prominent among the African American and Hispanic cohort. In the domain of knowledge deficits, patients were extremely worried about the risk of recurrence, and several opted for the most aggressive treatments to minimize their recurrence risk. At the same time, patients were generally fearful of receiving chemotherapy, often believing that it is the source of many of their physical complaints. Finally, one of the most prominent concerns was financial stress from medical bills. Conclusions: Uninsured and underinsured breast cancer survivors have specific needs different from the homogenous populations traditionally studied in breast cancer survivorship. Understanding how these needs differ will help us to better construct TSSCP’s for these populations.
Technical Success of ERCP in Patients with Periampullary Duodenal Diverticulum
Authors: M Kirca, A Zaheer, S McKiernan, N Keeling, N Mahmud
Journal: Endoscopy (2006)

Background: Periampullary duodenal diverticula (PAD) are considered to be associated with high failure rate of endoscopic retrograde cholangiopancreatography (ERCP) especially in elderly patients.
R4 Rgs Subfamily Proteins Negatively Regulates SDF-1/CXCR4 Signaling in CD34+ Hematopoietic Stem and Progenitor Cells
Authors: Kam Tong Leung, Yorky Tsin Sik Wong, Karen Li, Kathy Yuen Yee Chan, Xiao-Bing Zhang, Ting Fan Leung, Pak Cheung Ng, Chi Kong Li
Journal: Blood (2016)
Methods for the Separation of Epidermis from Dermis and Some Physiologic and Chemical Properties of Isolated Epidermis&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: J. Percy Baumberger, V. Suntzeff, E. V. Cowdry
Journal: JNCI Journal of the National Cancer Institute (1942)

Methods for the Separation of Epidermis from Dermis and Some Physiologic and Chemical Properties of Isolated Epidermis Get access J. Percy Baumberger, J. Percy Baumberger research associate Barnard Free Skin and Cancer Hospital, Washington University, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar V. Suntzeff, V. Suntzeff research associate Barnard Free Skin and Cancer Hospital, Washington University, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar E. V. Cowdry E. V. Cowdry director of research, professor of anatomy Barnard Free Skin and Cancer Hospital, Washington University, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 5, April 1942, Pages 413–423, https://doi.org/10.1093/jnci/2.5.413 Published: 01 April 1942
A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin
Authors: P. Bossi, D. Cortinovis, S. Fatigoni, M. Cossu Rocca, A. Fabi, P. Seminara, C. Ripamonti, S. Alfieri, R. Granata, C. Bergamini, F. Agustoni, P. Bidoli, F. Nolè, M.A. Pessi, F. Macchi, L. Michellini, F. Montanaro, F. Roila
Journal: Annals of Oncology (2017)

The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor quality of tested products limit the possibility to offer generalizable results.
Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia
Authors: Daniel L. Rolnik, David Wright, Liona C. Poon, Neil O’Gorman, Argyro Syngelaki, Catalina de Paco Matallana, Ranjit Akolekar, Simona Cicero, Deepa Janga, Mandeep Singh, Francisca S. Molina, Nicola Persico, Jacques C. Jani, Walter Plasencia, George Papaioannou, Kinneret Tenenbaum-Gavish, Hamutal Meiri, Sveinbjorn Gizurarson, Kate Maclagan, Kypros H. Nicolaides
Journal: New England Journal of Medicine (2017)

Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia.In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle.A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events.Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29 ; Current Controlled Trials number, ISRCTN13633058 .).
Randomized phase II study of regorafenib followed by cetuximab versus reverse sequence for wild-type <i>KRAS</i> metastatic colorectal cancer previously treated with fluoropyrimidine, oxaliplatin, and irinotecan (REVERCE).
Authors: Kohei Shitara, Kentaro Yamazaki, Hiroyuki Uetake, Takeshi Kato, Eiji Oki, Takeharu Yamanaka, Yasuo Ohashi, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2014)

TPS3662 Background: Regorafenib (RE) and cetuximab (CE) are both effective treatments for patients (pts) with metastatic colorectal cancer (mCRC) with the current standard sequence as CE followed by RE. For optimal continuum of care for mCRC pts, it is important to compare efficacy and safety of different sequential treatments. Furthermore, several possible biomarkers including oncogenic mutations and serum protein have been identified for both RE and CE treatment so far. The objective of this study is to evaluate the efficacy and safety of sequential treatment of RE followed by CE as compared with CE followed by RE. Exploratory objective is to investigate several biomarkers with an aim of producing findings that may be useful in elucidating the mechanism of resistance to each agent and contribute to future individualized therapy. Methods: This multicenter randomized phase II trial will enroll pts with KRAS wild-type mCRC after failure of chemotherapy including fluoropyrimidine, oxaliplatin, and irinotecan (UMIN000011294). Pts will be randomized (1:1; stratified by prior use of bevacizumab and intent to use irinotecan in combination with CE) to receive sequential treatment with RE followed by CE ± irinotecan or reverse sequence (CE ± irinotecan followed by RE). Primary endpoint is overall survival (OS). Secondary endpoints include time to sequential treatment failure (TTF), progression-free survival (PFS) of sequential treatment, anti-tumor effects (response rate, disease control rate) of RE or CE, safety, and patients reported outcome of quality of life (QOL). Exploratory endpoint is to investigate possible biomarkers including oncogenic mutations from circulating cell free DNA by liquid biopsy with serial measurement and multiple serum proteins related to epidermal growth factor receptor or vascular endothelial growth factor pathway change over time at several point of sequential treatment. To evaluate the similarity of OS between both arms (HR between 0.8 and 1.25), the sample size was planned as 180 subjects in total to observe 132 deaths with 1.5-year enrollment and subsequent 1.5-year follow-up periods. As of 21 Jan 2014, eight pts have been enrolled. Clinical trial information: UMIN000011294.
Safety of multiplex gene testing for inherited cancer risk: Interim analysis of a clinical trial.
Authors: Allison W. Kurian, Gregory Idos, Julie Culver, Charite Nicolette Ricker, Rachel Koff, Duveen Sturgeon, Katrina Lowstuter, Anne-Renee Hartman, Brian Allen, John Kidd, Courtney Rowe-Teeter, Kerry Kingham, Nicolette M. Chun, Iva Petrovchich, Meredith Mills, Christine Hong, Kevin McDonnell, Uri Ladabaum, James M. Ford, Stephen B. Gruber
Journal: Journal of Clinical Oncology (2016)

1503 Background: Sequencing more genes increases the chance of finding a pathogenic mutation and/or a variant of uncertain significance (VUS). Little is known about potential harms of multiplex testing for cancer risk, such as unwarranted surgery or adverse psychological effects. Methods: We conducted a prospective trial of sequencing 25 genes: APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53. Patients were eligible if they met standard testing guidelines or predictive models estimated ≥ 2.5% mutation probability. Participants were surveyed 3 months post-test: the Multidimensional Impact of Cancer Risk Assessment (MICRA) scale measured distress, uncertainty and positive experiences. We present a planned interim analysis after enrolling 1000 of 2000 total participants. Results: Of 1001 participants, 11.5% tested positive for a pathogenic mutation (Pos), 37.5% had VUS only and 51.0% tested negative (Neg). Median age was 51, 82% were female, 41% were Hispanic, and 73% had a personal cancer history. Self-reported preventive surgery rates were low at 3 months (mastectomy 1.0%, hysterectomy 0.4%, oophorectomy 0.4%), with no difference between VUS and Neg patients (p = 0.293). Most patients never or rarely had thoughts of cancer affecting daily activities (Pos 58.7%, VUS 70.8%, Neg 69.6%), never regretted testing (Pos 86.4%, VUS 86.6%, Neg 93.0%), and wanted to know all results, even those that doctors do not fully understand (Pos 86.6%, VUS 80.8%, Neg 80.3%). Pos patients had higher MICRA distress and uncertainty scores than VUS and Neg patients, whose scores did not significantly differ for either distress or uncertainty (p = 0.972, p = 0.108). Pos patients encouraged relatives to have genetic testing (81.8%) more than VUS (38.2%) or Neg patients (37.8%, p < 0.001). Conclusions: After multiplex testing of diverse patients, few reported preventive surgery at 3 months; VUS patients had no more distress, regret or uncertainty than Neg patients. Pos patients most often advised relatives to test, suggesting that participants understood the implications of test results. Follow-up for safety continues. Clinical trial information: NCT02324062.
The Joint Effect of Prenatal Exposure to Metal Mixtures on Neurodevelopmental Outcomes at 20–40 Months of Age: Evidence from Rural Bangladesh
Authors: Linda Valeri, Maitreyi M. Mazumdar, Jennifer F. Bobb, Birgit Claus Henn, Ema Rodrigues, Omar I.A. Sharif, Molly L. Kile, Quazi Quamruzzaman, Sakila Afroz, Mostafa Golam, Citra Amarasiriwardena, David C. Bellinger, David C. Christiani, Brent A. Coull, Robert O. Wright
Journal: Environmental Health Perspectives (2017)

Background: Exposure to chemical mixtures is recognized as the real-life scenario in all populations, needing new statistical methods that can assess their complex effects. Objectives: We aimed to assess the joint effect of in utero exposure to arsenic, manganese, and lead on children’s neurodevelopment. Methods: We employed a novel statistical approach, Bayesian kernel machine regression (BKMR), to study the joint effect of coexposure to arsenic, manganese, and lead on neurodevelopment using an adapted Bayley Scale of Infant and Toddler Development™. Third Edition, in 825 mother–child pairs recruited into a prospective birth cohort from two clinics in the Pabna and Sirajdikhan districts of Bangladesh. Metals were measured in cord blood using inductively coupled plasma-mass spectrometry. Results: Analyses were stratified by clinic due to differences in exposure profiles. In the Pabna district, which displayed high manganese levels [interquartile range (IQR): 4.8, 18μg/dl], we found a statistically significant negative effect of the mixture of arsenic, lead, and manganese on cognitive score when cord blood metals concentrations were all above the 60th percentile (As≥0.7μg/dl, Mn≥6.6μg/dl, Pb≥4.2μg/dl) compared to the median (As=0.5μg/dl, Mn=5.8μg/dl, Pb=3.1μg/dl). Evidence of a nonlinear effect of manganese was found. A change in log manganese from the 25th to the 75th percentile when arsenic and manganese were at the median was associated with a decrease in cognitive score of −0.3 (−0.5, −0.1) standard deviations. Our study suggests that arsenic might be a potentiator of manganese toxicity. Conclusions: Employing a novel statistical method for the study of the health effects of chemical mixtures, we found evidence of neurotoxicity of the mixture, as well as potential synergism between arsenic and manganese. https://doi.org/10.1289/EHP614
Après ingestion de caustique un second-look endoscopique prédit mieux le développement de sténoses oesophagienne et antropylorique qu’une endoscopie réalisée précocement
Journal: Endoscopy (2017)

Introduction: Une endoscopie oeso-gastroduodénale (EOGD) précoce (< 24 heures) est réalisée afin d’évaluer les lésions muqueuses après ingestion de caustique. L’objectif de cette étude était de comparer l’évaluation endoscopique réalisée à J1 et à J5 et de déterminer l’impact du second-look endoscopique sur la cicatrisation oesophagienne ou antro-pylorique.
Experience with aflibercept as a second line chemotherapy in metastatic colorectal cancer: Safety and efficacy in a real-life population
Authors: Encarnación González-Flores, Beatriz González-Astorga, Teresa Delgado Ureña Ma, Irene González Cebrián, Carmen Sánchez-Toro, Javier García-García, Verónica Conde
Journal: Annals of Oncology (2017)
Dual role for p16 in the metastasis process of HPV positive head and neck cancers
Authors: Rüveyda Dok, Mary Glorieux, Karolina Holacka, Marieke Bamps, Sandra Nuyts
Journal: Molecular Cancer (2017)

Several studies show that human papillomavirus (HPV) positive head and neck cancers (HNSCC) are typically characterized by low tumor and high regional node stages, intrinsically indicating high local metastatic potential. Despite this, the distant metastasis rates of HPV positive and negative HNSCC are similar. To date, majority of the studies focus on molecular characterization of HPV positive disease and on treatment outcome. Here we assessed the biological mechanisms of metastasis by combining in vitro and in vivo head and neck carcinoma xenograft models with patient data. We provide experimental evidence for a dual role of p16, a surrogate marker for HPV infections, in the metastasis process of HNSCC. We found that p16 regulates the invasiveness and metastatic potential of HNSCC cells by impairing angiogenesis. In parallel, we found that p16 is regulating the nodal spread by mediating lymphatic vessel formation through the upregulation of integrins. These findings not only provide understanding of the biology of the different dissemination patterns but also suggest that inhibition of lymphangiogenesis in HPV positive cancers and inhibition of angiogenesis in HPV negative cancers can form a treatment strategy against metastasis.
Rationale and Design of a Phase III Single-Arm Multicenter Study of Dabigatran Etexilate for the Secondary Prevention of Venous Thromboembolism in Children
Authors: Matteo Luciani, Manuela Albisetti, Ivan Manastirski, Martina Brueckmann, Savion Gropper, Igor Tartakovsky, Bushi Wang, Branislav Biss, Lesley G Mitchell, Fenglei Huang, Jacqueline ML Halton, Leonardo R. Brandão
Journal: Blood (2016)
Salvage of a dislodged hepaticogastrostomy stent in the peritoneum with NOTES
Authors: Khanh Pham, Dag Hoem, Arild Horn, Georg Dimcevski
Journal: Endoscopy (2017)

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is a technique to create a fistula between the stomach and the left intrahepatic bile duct. The technical success rate is high, reported to be 87 % – 89.5 % in expert hands, but the drawback is the procedure-related adverse event rate of 27 % [1] [2], with possible events including pneumoperitoneum, choleperitoneum, infection, stent dysfunction, and death [3]. In natural orifice transluminal endoscopic surgery (NOTES), an intentional perforation in the bowel is created to access the peritoneal cavity with an endoscope. We describe here a novel NOTES technique to salvage a misplaced HGS stent from the peritoneal cavity.