tbuckley/cabot-search huggingface dataset:
Outcomes in older patients with localized gastric adenocarcinoma treated preoperatively.
Authors: Nikolaos Charalampakis, Lianchun Xiao, Quan Lin, Elena Elimova, Yusuke Shimodaira, Hironori Shiozaki, Bruce D. Minsky, Prajnan Das, Wayne Lewis Hofstetter, Stephen Swisher, Heath Devin Skinner, Dipen M. Maru, Aurelio Matamoros, Mariela Blum, Jeffrey H Lee, Brian Weston, Manoop S. Bhutani, Paul F. Mansfield, Brian D. Badgwell, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2016)

4029 Background: Older patients with localized gastric adenocarcinoma (LGAC) have substantial postoperative morbidity and mortality; however, postoperative outcomes of these patients who receive preoperative chemotherapy and/or chemoradiation have not been reported. We examined the impact of age at baseline on potential predictors of postoperative outcomes. Methods: Patients with LGAC who were first treated with chemotherapy and/or chemoradiation followed by surgery (n = 203) formed two groups: (1) ≥ 65 years old (n = 70) and (2) < 65 years old (n = 133). We assessed postoperative morbidity and mortality as well as overall survival (OS) and progression-free survival (PFS). Potential predictors of 90-day postoperative outcomes were identified i) by age groups and ii) other clinical covariates. Descriptive statistics and survival analyses were utilized. Results: 90-daypostoperative morbidity was similar in older and younger patients (61% vs 58%; p = 0.6549). 90-day mortality was similar (3% vs 0%; p = 0.1178). Major Clavien grade III/IV complications were similar in older patients (17% vs 12%; p = 0.3919). OS and PFS were also similar for both groups (p = 0.8629 and p = 0.558, respectively). Other factors, such as Charlson comorbidity index (p = 0.0114), length of hospital stay (p = 0.0009), median operative time (p = 0.006) and presence of diabetes (p = 0.0282) were strong predictors of postoperative complications. Conclusions: Our data suggest that there is no significant difference in postoperative morbidity and mortality between younger and older patients who have localized gastric adenocarcinoma and received preoperative treatment. Rather than age, comorbidities have more impact on postoperative complications and outcomes.
Abstract 2309: T-cell development from T cell-derived induced pluripotent stem cell
Authors: Sjoukje J.C. van der Stegen, Maria Themeli, Justin Eyquem, Jorge Mansilla-Soto, Michel Sadelain
Journal: Cancer Research (2016)

Abstract The ability to differentiate T cells of defined specificity and function from T-cell derived induced pluripotent stem cells (TiPSC) may be useful for the treatment of a range of pathologies, including cancer, infection and immune deficits. We recently reported that genetic engineering of TiPSC to express a Chimeric Antigen Receptor (CAR) is an effective strategy to combine the unlimited availability of TiPSC and facilitate reprogramming of the T cell specificity and functional potential. In vivo, CD19-retargeted human TiPS-derived CAR T cells (CARTiPSC-T) display therapeutic potency in a lymphoma model. Surprisingly, despite expression of the endogenous αβ TCR, the CARTiPSC-T cells possessed innate-like phenotype and function, most similar to γδ T cells. Although innate T cells have anti-tumor activity, they lack some vital features for therapeutic efficacy including long-term memory and in vivo persistence, which characterize mature CD8+ and CD4+ αβ TCR T cells. Additional research into the mechanisms underlying in vitro T cell differentiation of TiPSC is required to improve the development of mature TCRαβ T cells and facilitate the employment of their therapeutic potential. T cell lineage determination depends in part on the balance between Notch and TCR signaling, we are investigating their respective roles, as well as that of the CAR, in determining lineage commitment. We hypothesize that the combined CAR and early CD3/TCRαβ expression disrupts the TCR/Notch signaling balance, prohibiting mature TCRαβ T cell development. To study the effects of the different Notch ligands, TiPSC were differentiated on OP9 cells expressing one of four Notch ligands (DLL1, DLL4, Jagged-1 or Jagged-2). Preliminary data suggests that DLL4 is able to facilitate T cell development to CD4/CD8 double positive (DP) stage, however, this is hindered by CAR expression. To determine the role of early TCRαβ expression, elimination of TCRαβ expression was facilitated by targeted disruption of the TCRα constant region using the CRISPR/Cas9 system. Elimination of early TCRαβ expression showed improved development towards DP stage of TiPSC on OP9-DLL1. TiPSC are a valuable system for the study of human T cell differentiation. In addition, and most importantly they are further amenable to genetic engineering with TCRs or CARs, which may be useful for the generation of therapeutic “off-the-shelf”, antigen-specific T cells. Citation Format: Sjoukje J.C. van der Stegen, Maria Themeli, Justin Eyquem, Jorge Mansilla-Soto, Michel Sadelain. T-cell development from T cell-derived induced pluripotent stem cell. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2309.
Stem Cell Extracellular Vesicles: Extended Messages of Regeneration
Authors: Milad Riazifar, Egest J. Pone, Jan Lötvall, Weian Zhao
Journal: The Annual Review of Pharmacology and Toxicology (2016)

Stem cells are critical to maintaining steady-state organ homeostasis and regenerating injured tissues. Recent intriguing reports implicate extracellular vesicles (EVs) as carriers for the distribution of morphogens and growth and differentiation factors from tissue parenchymal cells to stem cells, and conversely, stem cell-derived EVs carrying certain proteins and nucleic acids can support healing of injured tissues. We describe approaches to make use of engineered EVs as technology platforms in therapeutics and diagnostics in the context of stem cells. For some regenerative therapies, natural and engineered EVs from stem cells may be superior to single-molecule drugs, biologics, whole cells, and synthetic liposome or nanoparticle formulations because of the ease of bioengineering with multiple factors while retaining superior biocompatibility and biostability and posing fewer risks for abnormal differentiation or neoplastic transformation. Finally, we provide an overview of current challenges and future directions of EVs as potential therapeutic alternatives to cells for clinical applications.
PWE-441 Colonoscopy procedures with and without sedation and pain scores: Abstract PWE-441 Table 1
Authors: S Birdi, I Stasinos, A Muller
Journal: Gut (2015)

<h3>Introduction</h3> Retrospective data collection to compare pain scores during colonoscopy procedures performed with and without sedation in both Bowel cancer screening programme (BCSP) and Non bowel cancer screening programme (Non BCSP) patient groups. <h3>Method</h3> Data collected retrospectively for all patients who underwent colonoscopy procedures at East Kent Hospitals NHS Trust from August 2014 to October 2014. Data collected from Unisoft in endoscopy department before C02 was introduced. Total number of colonoscopy procedures performed 1903 over 3 month period. 179 patients excluded because of incomplete endoscopy reports including comfort scores. Total number of patients included 1724. Number of patients in Non BCSP group and BCSP group were 1565 and 159 respectively. Pain score completed post colonoscopy procedure. Patient pain scores were recorded from 0–3 (no discomfort, minimal discomfort (One or two episodes of mild discomfort, well tolerated), moderate discomfort (More than two episodes of discomfort, adequately tolerated), Extreme or significant discomfort). <h3>Results</h3> Non BCSP (Non Bowel Cancer screening programme) Group <b>a) Sedated patients</b>1136 (72.58%), Male: female (486:650), Average age and Standard deviation (61.66, 13.4) <b>b) Unsedated patients</b>429 (27.42%), Male: female (277:152), Average age and standard Deviation (71.5, 4.95) BCSP (Bowel cancer screening Programme) Group <b>a) Sedated patients</b>104 (65%), (Male: female 49:55), Average age and standard deviation (72.5, 3.53) b) <b>Unsedated patients</b>55 (35%), (Male: Female 45:10) Average age and standard deviation (67.1, 0.71) Pain scores for sedated and unsedated patients in Non BCSP and BCSP groups are shown in Table 1below <h3>Conclusion</h3> Unsedated colonoscopy is a safe, effective and well tolerated procedure in the right patient. Male gender is predominant in patients underwent colonoscopy without sedation in both BCSP and Non BCSP. Nearly 1/3<sup>rd</sup>of patients in symptomatic Non BCSP and BCSP group completed the procedure without sedation without more discomfort than those received sedation (although this may reflect different groups of patients). Despite the used greater intervention in bowel cancer screening patients after pain scores with and without sedation were similar to the symptomatic group. <h3>Disclosure of interest</h3> None Declared.
Efficacy in six courses of nonmethotrexate three-drug chemotherapy and surgery in osteosarcoma: 25-year experience.
Authors: Rejin Kebudi, Inci Ayan, Harzem Ozger, Fatma Betul Cakir, Omer Gorgun, Sema Buyukkapu Bay, Bilge Bilgic
Journal: Journal of Clinical Oncology (2015)

10050 Background: Chemotherapy and surgery are the mainstay of osteosarcoma (OS) treatment. Using 2-4 drugs and short or long duration in chemotherapy protocols have been evaluated in various trials. A metaanalysis (Anninga JK, 2011) has reported, 3-drug regimen is better than 2, but not inferior than 4-drug. Our study aims to evaluate the outcome of Osteosarcoma (OS) patients treated with a nonmethotrexate 3-drug regimen and surgery. Methods: Children and adolescents with oteosarcoma treated between January,1990- January,2015 at Istanbul University, Oncology Institute were retrospectively evaluated in terms of demographic features and survival outcomes. The patients recieved 6 courses of a 3 drug regimen comprising of ifosfamide 1.8 g/m2/d x 3 days, epirubicin 90 mg/m2/d and sisplatinum 100mg/m2/d administered 3-pre and 3-postoperatively. Methotrexate was not in the protocol because drug levels could not be monitored in the 1990's at our center. Since 2012, mifamurtide was added to the protocol postoperatively for nonmetastatic patients. Results: 189 children (105 boys, 84 girls) with a median age of 12 years (3-18yrs) were evaluated. 151 (80%) were non-metastatic and 38 metastatic. Median follow-up was 3,6 years (1mo.-24 yrs). 91.5 % had limb salvage surgery. Relapse/progressive disease was observed in 69 patients at a median 15 months (1mo-63 mo). The 5 and 10-year overall survival and event free survival for the whole group were (OS) 63.1% and 60.5%, and (EFS) 58.8% and 57% respectively. In non-metastatic and in metastatic patients, 5-year OS was 73.8 and 23.9% , 5-year EFS was 69.4% and 20.8%; respectively (p = 0.0001). In 25 nonmetastatic patients recieving chemotherapy and mifamurtide 2-year OS and EFS were 90.9% and 85.5% respectively at a median of 20 months. Conclusions: A 3-drug combination of cisplatin,epirubicin,ifosfamide given for 6 courses is an effective, reasonably well tolerated regimen for osteosarcoma; and combined with surgery in experienced hands results in survival rates comparable to other studies in the literature. Longer follow up is needed to assess the contribution of mifamurtide on outcome. Presence of metastasis is associated with poor outcome.
Predictors of perceived stigmatization in patients with psoriasis
Authors: S. van Beugen, H. van Middendorp, M. Ferwerda, J.V. Smit, M.E.J. Zeeuwen-Franssen, E.B.M. Kroft, E.M.G.J. de Jong, A.R.T. Donders, P.C.M. van de Kerkhof, A.W.M. Evers
Journal: British Journal of Dermatology (2016)

The physical appearance of psoriasis can be cosmetically disfiguring, resulting in a substantial social burden for patients. An important aspect of this burden is the experience of stigmatization. While stigmatization is known to be disabling and stressful for patients, little is known about its correlates, and effective interventions are lacking. To examine predictor variables for perceived stigmatization in psoriasis. Questionnaires were administered to 514 patients with psoriasis in a cross‐sectional study. Zero‐order correlation and multiple‐regression analyses were conducted including sociodemographic, disease‐related, personality, illness cognitions and social support predictor variables. Stigmatization was experienced by 73% of patients to some degree, and correlated with all five categories of predictor variables. In multiple‐regression analyses, stigmatization was associated with higher impact on daily life; lower education; higher disease visibility, severity and duration; higher levels of social inhibition; having a type D personality; and not having a partner. The results indicate that perceived stigmatization is common in psoriasis, and can be predicted by sociodemographic, disease‐related and personality variables. These predictor variables provide indications of which patients are especially vulnerable regarding perceived stigmatization, which might be used in treatment.
UK response to serial drug company misdemeanour—no action, no shame
Authors: Alain Braillon, John H Noble, Susan Bewley
Journal: BMJ (2016)

The Association of the British Pharmaceutical Industry (ABPI) has suspended Astellas for inviting more than 100 clinicians to a sham “educational event” meeting in Milan. How is Astellas’s recidivist record ignored by so many professionals who continue to take up invitations? Why this relative inertia of …
Proximal esophageal cancer missed during esophagogastroduodenoscopy: should the detection of an inlet patch be added to the quality criteria for upper gastrointestinal endoscopy?
Authors: Emma Paulides, Nanne de Boer, Matthijs Grasman
Journal: Endoscopy (2016)

A 75-year-old woman was investigated by the pulmonologist for pulmonary abnormalities and weight loss. In the past she had undergone repeated endoscopic rubber-band ligations for bleeding esophageal varices. A combined positron emission tomography–computed tomography (PET-CT) scan revealed intense fluorodeoxyglucose (FDG) avidity in the proximal esophagus. An esophagogastroduodenoscopy (EGD) showed a squamous cell carcinoma just distal to the upper esophageal sphincter. Remarkably, an EGD 2 months earlier had been reported to be without abnormalities.
Estimating the Influence of Obesity on Cancer Risk: Stratification by Smoking Is Critical
Authors: Mingyang Song, Edward Giovannucci
Journal: Journal of Clinical Oncology (2016)

Tobacco use is well known to be the most common cause of cancer in populations in which its use is widespread. More recently, excess bodyweight has been identified as an important cause of cancer incidence and mortality (Table 1). The population-attributable fraction (PAF) of cancer incidence, including all cancers in Table 1 except those in the prostate and liver, as a result of high body mass index (BMI) has been estimated to range from 4% to 6% in highincome countries and remain lower than 1% to 2% in moderateor low-income countries by using BMI estimates from 2002 and cancer incidence data in 2012. In a recent summary, Flegal et al presented results for the proportion of all cancer incidence attributable to excess body weight, and estimates ranged from20.2% to 8%. To achieve maximal generalizability, these estimates were based on the entire population, with smokers and nonsmokers combined. In contrast, when stratified by smoking, PAF estimates tend to be much higher for nonsmokers. For example, in the Cancer Prevention Study II, a prospective study led by the American Cancer Society in 1982, the PAF of total cancer mortality as a result of high BMI was 4.2% in men and 14.3% in women in the entire population, but these estimates increased to 14.2% and 19.8%, respectively, in the population that was limited to nonsmokers. This difference is not trivial, especially for men, where a 3.5-fold difference in the magnitude of PAF is observed when including or excluding smokers. Clearly, tobacco use has a profound influence in considering the association between body mass and cancer risk. Is it more appropriate to consider the PAF in the entire population or to stratify by smoking status? Some have argued that estimation on the basis of the entire population is more legitimate because it preserves generalizability. For example, Flegal et al argue that not all cancers are associated with obesity and, therefore, estimates on the basis of the entire population are most appropriate. In this commentary, however, we argue that from biologic, epidemiologic, clinical, and public health perspectives, effect estimates for excess body weight on cancer risk should be given separately for smokers and nonsmokers, and results given for the entire population are generalizable only in the sense that they are wrong for everyone.
Testing for dabigatran and rivaroxaban by clinical laboratories
Authors: Elizabeth M. Van Cott, Kristi J. Smock, Dong Chen, Peihong Hsu, Nicole D. Zantek, Piet Meijer
Journal: American Journal of Hematology (2016)

Rivaroxaban and dabigatran are among the newest anticoagulants, and measuring their concentration in patients is a new challenge for clinical laboratories. We analyzed data from the ECAT proficiency program to determine how well the assays are performing in clinical laboratories internationally. Most laboratories received a passing grade ( Z score &lt;3) for the results of their dabigatran and rivaroxaban testing. Failing Z scores were not associated with any particular method. With dabigatran, some homemade calibrators gave higher results than the commercially available calibrators. There were no significant differences among the instruments or the 5 reagents in use, but results showed inter‐laboratory variability that could have clinical significance. The 3 reagents with the lowest number of users had poor inter‐laboratory precision. Ten different anti‐Xa reagents were in use for rivaroxaban testing. One reagent gave lower results than other reagents at 100 ng/mL but not at 300 ng/mL. There were no significant differences among the different rivaroxaban calibrators or instruments. In conclusion, inter‐laboratory precision could be improved for both dabigatran and rivaroxaban assays. Homemade dabigatran calibrators differed from commercially available calibrators, and there was a statistically significant difference between some of the rivaroxaban reagents. About 10% of results received failing Z scores or passed but fell in a range that require the laboratory to investigate for bias or other inaccuracy in their method. Am. J. Hematol. 91:E464–E467, 2016. © 2016 Wiley Periodicals, Inc.
Performance of a 31-gene expression profile in a previously unreported cohort of 334 cutaneous melanoma patients.
Authors: Jonathan S. Zager, Jane Messina, Vernon K. Sondak, Laura Ferris, Robert W. Cook, Brooke Middlebrook, Clare Johnson, Derek Maetzold, Federico A. Monzon, Jeffrey D. Wayne, Pedram Gerami
Journal: Journal of Clinical Oncology (2016)

9581 Background: A 31-gene expression profile (GEP) that provides a binary outcome of low or high risk of distant metastasis (DM) within 5 years of diagnosis has been validated as an independent predictor of distant metastasis free (DMFS) and overall survival (OS). We present analysis of DM prognostication in a previously unreported cohort of cutaneous melanoma (CM) patients. Methods: 334 CM primary tumors from 12 centers were analyzed as part of an IRB-approved archival tissue study. Quantitative RT-PCR and predictive modeling were performed as previously described (Gerami, JAAD, 2015) and classified tumors as low risk Class 1 or high risk Class 2. Results for Cox regression survival analysis are reported. Results: Cox univariate regression analysis of the cohort indicated that Breslow's thickness (BT), ulceration (U), mitotic rate (MR), sentinel lymph node (SLN) status and GEP class were significant predictors of DM risk (p < 0.008 for all; median BT = 1.5mm, median follow up = 5.3 years). 156 (47%) cases with documented BT, U, MR, SLN status and GEP class were included in multivariate analyses. A documented distant metastatic event was reported for 46 of 156 (29%) cases. Multivariate analysis of all factors resulted in a significant association of SLN status (p = 0.002) and GEP (p = 0.031) with DM (table). 13 of 83 (16%) SLN negative cases had a DM event, and 10 (77%) of these had a Class 2 GEP result. Accuracy of DM prediction by GEP showed 76% sensitivity, 55% specificity, 42% positive and 85% negative predictive values compared to 72%, 64%, 45% and 84%, respectively, for SLN. Conclusions: GEP offers prognostic information that complements conventional staging in order to better identify CM patients at risk for distant metastasis. Results achieved in this multicenter study parallel previously reported performance of the GEP. Prospective evaluation of the utility of closer surveillance for detection of DM, and the potential benefits of adjuvant treatment, for Class 2 patients is warranted. Variable Multivariate P value HR CI Breslow's thickness > median 0.628 1.2 0.5-2.5 mitotic rate > 1/mm2 0.915 1.0 0.4-2.4 ulceration present 0.339 1.4 0.7-2.6 sentinel lymph node positive 0.002 2.9 1.5-5.1 GEP Class 2 0.031 2.4 1.1-5.3
Impact of Chemotherapy Delay on Overall Survival for AML with I DH1/2 Mutations: A Study in Adult Chinese Patients
Authors: Jing Han Wang, Qi Guo, Zhi Xin Ma, Qiu Ling Ma, Meng Xia Yu, Xiu Feng Yin, Sha Sha Lu, Qiong Hong Xie, Yue Hong Jiang, Dan Shen, li Ya Ma, Hui Shi, Wen Juan Yu, Ye Jiang Lou, Ying Li, Min Yang, Gai Xiang Xu, Li Ping Mao, Jian Hu Li, Fan Ping Wang, Dong Mei Wang, Ju Ying Wei, Hong Yan Tong, Jian Huang, Jie Jin
Journal: Blood (2015)