tbuckley/cabot-search huggingface dataset:
PWE-156 Common bile duct stones; a surgical disease
Authors: Z Khanzada, R Morgan
Journal: Gut (2012)

<h3>Introduction</h3> There is no clear consensus, from previous randomised controlled trials and meta-analyses, on the optimum treatment modality for common bile duct (CBD) stones. This study aimed to evaluate the single-stage laparoscopic approach to the management of CBD stones, as treatment of choice in patients who are fit for surgery, and to determine what results can be achieved when this treatment modality is chosen. <h3>Methods</h3> The study was performed on a series of patients, both elective and emergency, who underwent laparoscopic CBD exploration, using prospectively collected data. Inclusion criteria were all patients who underwent laparoscopic CBD exploration (along with laparoscopic cholecystectomy) following a positive on-table intra-operative cholangiogram (performed selectively on patients with suspected CBD stones). The rate of successful CBD clearance was measured; markers of unsuccessful CBD clearance included finding of residual stones on T tube cholangiogram or MRCP, and the need for post-operative ERCP for clearance of either stones known to be left behind at the end of the procedure, or presenting symptomatically in the post-operative period. Morbidity was measured by identifying complications, including both intra-operative and post-operative, by case note review. Hospital stay was recorded from the date of admission to the date of discharge. Mortality was measured from hospital mortality audit records. Outcomes were noted in both elective and emergency situations. Finally a comparison of our experience was made with the recent published data. <h3>Results</h3> In a series of 140 patients, successful clearance of CBD stones was achieved in 95.7% of cases. Retained stones were found in 3.6% cases and another 3.6% developed post-operative complications. A post-operative mortality rate of 1.4% was recorded, which was due to reasons not directly related to the procedure. The most common length of stay was 2 days, although the median length of stay was 4 days. 25% of cases were done as emergencies and 75% were elective. Overall conversion rate to open surgery was up to 12.8%, which mainly occurred in the emergency cases. <h3>Conclusion</h3> Laparoscopic CBD exploration can be chosen as a safe and effective first line treatment for CBD stones; better results can be anticipated in elective (compared with emergency) patients. <h3>Competing interests</h3> None declared.
Diesel exhausts may expose city dwellers to raised cancer risk
Authors: N. Hawkes
Journal: BMJ (2012)

Exposure to diesel exhaust may raise the risk of lung cancer in urban populations, conclude the authors of two new studies that have been hotly contested in the United States.

By examining the health records of more than 12 000 workers in the US mining industry who have been exposed to diesel exhausts from mining vehicles and machinery, researchers at the US National Institute for Occupational Safety and Health and the US National Cancer Institute found that among underground workers there was a small but significant raised risk of lung cancer ( Journal of the National Cancer Institute doi:10.1093/jnci/djs034).

There was no increase in all cause mortality, which was lower than expected, consistent with the “healthy worker” effect. But in a cohort study the authors found that the standardised mortality ratio for lung cancer (203 deaths) was elevated by 26% (1.26 (95% confidence interval 1.09 to 1.44)) among all workers, including those who had never worked underground ( Journal of the …
Small-bowel perforation in a patient with Roux-en-Y anatomy for Peutz–Jeghers polyps after spiral enteroscopic investigation
Authors: X.-B. Li, L.-Y. Gu, Y. Song, Y.-J. Gao, Z.-Z. Ge
Journal: Endoscopy (2011)

Spiral enteroscopy is a new technique for diagnosis and treatment of small-bowel disease. In July 2009, a 19-year-old woman with Peutz–Jeghers syndrome was sent to our hospital for screening and treatment. The patient had undergone segmental resection of the distal jejunum, 4 years previously, for acute intestinal obstruction due to large Peutz–Jeghers polyps.
Abstract 3977: Gene-expression signature specifically associated with triple-negative breast cancer pertaining to asian ethnicity
Authors: Yao-Yin Chang, Yu-Ho Kuo, Hung Lee Chen, Liang-Chuan Lai, Wen-Hung Kuo, Chuhsing Kate Hsiao, Eric Y. Chuang, King-Jen Chang
Journal: Cancer Research (2010)

Abstract Triple-negative breast cancer is a subtype of breast cancer with strong aggressiveness of tumor behavior and distinct patterns of metastasis. This unique phenotype of breast cancer is given by its clinically negative expression of estrogen receptor (ER), progesterone receptors (PR), and HER2 protein. Triple-negative breast cancer patients often suffer from ineffective hormone therapies, high recurrence rate, and a predilection for visceral metastasis. An accurate gene-expression signature specifically associated with triple-negative breast cancer will facilitate the identification of the existence of this disease and provide insights of its etiology. DNA microarray analysis was used to evaluate gene-expression profiles of 181 Asian breast cancer patients. There were 48 breast cancer patients who were triple-negative, and 133 of them were non-triple-negative. Several clinical information were matched in each group, including lymphovascular invasion, age, stage, grade, tumor size, tubule formation, nuclear pleomorphism, and mitotic count. After all 181 microarray data were normalized with quantile normalization, significantly expressed genes differentiated from the triple-negative group and non-triple-negative group were extracted using SAM (Significant Analysis of Microarray) and T-test. A panel of 50 genes was selected as the gene-expression signature for triple-negative breast cancer for Asian ethnicity, based on their unique patterns of gene-expression data using hierarchical clustering. Pathway analysis of the signature genes for triple-negative breast cancer was then performed in the lab. Genetic interactions of significantly expressed genes among different pathways found in this study will be shown and elaborated on the poster. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3977.
954 PRIMARY SCLEROSING CHOLANGITIS WITH FEATURES OF AUTOIMMUNE HEPATITIS: CHARACTERISTICS AT FIRST PRESENTATION AND LONG TERM OUTCOME IN A LARGE, MULTICENTER COHORT FROM GERMANY
Authors: K. Schulze, T. Weismüller, P. Hübener, R. Zenouzi, D. Gotthardt, P. de Leuw, A. Teufel, V. Zimmer, C. Rust, L. Tharun, A. Quaas, F. Lammert, P. Galle, C. Sarrazin, M. Manns, A. Lohse, C. Schramm
Journal: Journal of Hepatology (2013)
Scientists Study Families in Pursuit of Cancer Genes
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Scientists Study Families in Pursuit of Cancer Genes Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 2, 16 January 1991, Pages 82–83, https://doi.org/10.1093/jnci/83.2.82 Published: 16 January 1991
A Prospective Study on How Symptoms in a Network Predict the Onset of Depression
Authors: Lynn Boschloo, Claudia D. van Borkulo, Denny Borsboom, Robert A. Schoevers
Journal: Psychotherapy and Psychosomatics (2016)

To explain the overt heterogeneous nature of major depressive disorder (MDD), it could be valuable to focus on individual symptoms [1]. Recent research, for example, showed that MDD symptoms differ in their underlying biology, risk factors and psychosocial impairments [for a review, see [2]]. In addition, the presence of specific symptoms (e.g. psychomotor agitation) may have important clinical implications, such as expectations regarding the response to antidepressants [3].
Side Glance: Laboratory-Bred Mice
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Side Glance : Laboratory-Bred Mice Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 4, 15 February 1995, Pages 248–249, https://doi.org/10.1093/jnci/87.4.248 Published: 15 February 1995
PTH-118 Albi score predicts survival in patients with bclc 0/a stage hepatocellular carcinoma (HCC) independently of child pugh (CP) score and treatment allocation
Authors: S Onali, A Marshall, D Sharma, P O’Donoghue, E Dannhorn, P Johnson, J O’Beirne
Journal: Gut (2015)

<h3>Introduction</h3> BCLC 0/A stage HCC patients are considered candidates for curative treatments. Within the BCLC classification, liver function is assessed by CP score despite this score not being derived from patients with HCC. ALBI is a novel evidence based score derived from a large cohort of HCC patients and has been shown to define different prognostic groups even within CP A.<sup>1</sup>We studied the performance of ALBI score in a well characterised cohort of patients with BCLC 0/A stage HCC to determine if ALBI score impacted on prognosis. <h3>Method</h3> Consecutive patients with BCLC 0/A HCC, evaluated between 2010–2014 at the Royal Free Hospital were included. All patients had a performance score of 0 and were undergoing evaluation for potential resection. Patients were considered resectable if they had HVPG ≤10 mmHg or HVPG ≥10 mmHg with good liver function as assessed by ICG clearance. ALBI score was calculated at the time of HVPG and ICG clearance measurement and divided into 3 grades as per published cutoffs. Kaplan Meier and Cox regression analysis were used to assess the impact of ALBI on survival. <h3>Results</h3> 67 patients were included: 64 (95.5%) were CP A, 3 (4.5%) were CP B. 60 (89%) had uninodular tumour and 7 (10.4%) multifocal (≤3 tumours ≤30 mm). 46 (69%) underwent resection, 4 (6%) RFA, 9 (14%) TAE, 3 (5%) OLT, 3 (5%) either no treatment or undergoing evaluation. Median follow up was 9 months (13–54). 10 (15%) patients died during follow up. Cause of death was HCC-related n = 4, liver failure n = 4, non-liver related n = 2. In Kaplan Meier analysis CP score was not associated with difference in survival. Cox regression analysis revealed ALBI score as the only significant factor related to survival and was independent of CP score and treatment allocation (p = 0.002, OR=15, 95% CI=3–80). Of patients with ALBI grade 1, 44 (83%) were considered suitable and underwent resection vs only 2 (14%) with ALBI 2. One-year survival was 88% in patients with ALBI grade 1 and 43% in patients with ALBI grade 2 (p = 0.002). <h3>Conclusion</h3> In patients with BCLC 0/A stage HCC ALBI score clearly defines patients with different prognosis regardless of Child Pugh score and treatment allocation. ALBI grade 2 patients are very rarely suitable candidates for resection. ALBI score is more informative than Child Pugh score in patients with early stage HCC and may be useful in determining treatment allocation. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Johnson PJ, <i>et al</i>. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. <i>J Clin Oncol</i>. 2015 Feb 20;33(6):550–8
Rectal carcinoid tumor: a delayed localized recurrence 23 years after endoscopic resection
Authors: Stephanie Judd, Sharad Nangia, Edi Levi, Fadi Antaki
Journal: Endoscopy (2014)

Rectal carcinoid tumors are rare representing approximately 2 % of rectal malignancies [1]. While treatment approaches vary and can include endoscopic or surgical resection, small (< 1 cm) carcinoid tumors have extremely low rates of local recurrence and metastasis [1] [2] [3]. Our case is the first describing a delayed recurrence of rectal carcinoid tumor more than 20 years after initial endoscopic resection.
Transient Elastography (FIBROSCAN®) – Predictor of Hepatocellular Carcinoma Prognosis in Patients Referred to Surgical Treatment
Authors: Suceveanu Andra Iulia, Mazilu Laura, Suceveanu Adrian Paul, Parepa Irinel, Catrinoiu Doina, Tofolean Doina, Voinea Felix
Journal: Annals of Oncology (2014)
Abstract 4840: 2-Deoxy-D-glucose induces autophagy through endoplasmic reticulum stress rather than by lowering ATP
Authors: Haibin Xi, Metin Kurtoglu, Huaping Liu, Medhi Wangpaichitr, Min You, Niramol Savaraj, Theodore J. Lampidis
Journal: Cancer Research (2010)

Abstract Based on emerging evidence that oncogenes direct increased glucose metabolism in tumor cells, the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG) appears to be a promising drug to selectively target cancer cells. 2-DG however, not only blocks glycolysis and reduces cellular ATP production but also interferes with N-linked glycosylation, thereby inducing endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). Both bioenergetic challenge and ER stress/UPR have been shown to activate autophagy, a bulk cellular degradation process that plays either a pro- or anti-death role. This led us to investigate the following, 1) which pathway that 2-DG interferes with is responsible for stimulating autophagy, and 2) the role of autophagy in modulating 2-DG-induced cellular responses and toxicity. In four cancer cell lines (1420, MDA-MB-435, SKBR3 and T98G) we find that 2-DG upregulates autophagy (LC3B II), increases the ER stress/UPR markers, Grp78 and CHOP, and lowers ATP levels. Addition of exogenous mannose reverses 2-DG-induced autophagy and expression of GRP78 and CHOP but does not recover the lowered levels of ATP. Additionally, when autophagy is either blocked or enhanced by 3-methyladenine (3-MA) or rapamycin, respectively, 3-MA increases whereas rapamycin reduces cancer cell sensitivity to 2-DG. In support of these results, knock down of autophagy-related gene 7 (Atg7) with small interfering RNAs (siRNAs) increases sensitivity to 2-DG in 1420 cells, which correlates with increases in the ER stress/UPR markers as well as the apoptotic marker, cleaved caspase 3. Overall, these results indicate that the major mechanism by which 2-DG stimulates autophagy is through ER stress/UPR, and autophagy protects cells from 2-DG-induced toxicity through relief of ER stress. Thus, combining autophagy inhibitors with 2-DG may be useful clinically. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4840.
THU0090 Cardiovascular Morbidity in Patients with Ankylosing Spondylitis: A Population-Based Cohort Study
Authors: I. Essers, C. Stolwijk, A. van Tubergen, A. Boonen, M.L. De Bruin, M. Bazelier, F. de Vries
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> It is well recognized that rheumatoid arthritis is an independent risk factor for cardiovascular (CV) disease. For ankylosing spondylitis (AS), the literature on this risk is relatively scarce, and shows conflicting results. Furthermore, these studies did not explore the role of non-steroidal anti-inflammatory drugs (NSAIDs) use. <h3>Objectives</h3> To examine the incidence and risk of ischemic heart disease (IHD) and acute myocardial infarction (AMI) in patients with AS compared with population-based controls, and explore the role of recent NSAID use. <h3>Methods</h3> All incident patients with AS from the UK Clinical Practice Research Datalink (1987-2012) were matched with up to 7 persons without AS by year of birth, sex and practice. Incidence rates, cumulative incidence rates and hazard ratios (HR) for the development of IHD and AMI were calculated, with time-varying adjustments for age, sex, comorbidity and drug use. When further exploring the role of NSAIDs on the risk of IHD, patients with AS were stratified according to the use of coxibs, naproxen or other traditional NSAIDs in the previous 3 months. <h3>Results</h3> In total, 3,809 patients with AS (mean age at index date 43.7 years, 70.5% male, median duration of follow-up 6.6 years) were matched with 26,197 control subjects. At baseline, 4.3% of the patients had IHD compared with 3.4% of the controls (p-value&lt;0.01), and 1.8% of the patients had AMI compared with 1.4% of the controls (p-value=0.02). After excluding patients with IHD and/or AMI at baseline, the incidence rates were 1.2/1000 person years (pys) and 0.9/1000 pys for IHD and AMI, respectively. The age-gender adjusted (adj.) HR of developing IHD was 1.2 (95% Confidence interval [CI] 1.0-1.5), and for AMI 0.9 (95% CI 0.7-1.3). After statistical adjustment for recent use of NSAIDs, the increased risk of IHD disappeared (adj. HR 1.1 95% CI 0.9-1.3). In the fully adjusted model, the risk remained almost unchanged (adj. HR 1.0, 95% CI 0.8-1.3). In patients with AS, stratification according to the use of coxibs, naproxen or other NSAIDs, showed that exposure to NSAIDs other than naproxen or coxibs increased the risk of IHD to 1.5 (95% CI 1.1-2.1) compared with controls irrespective of their NSAID use. However, within patients with AS this risk was not different from AS patients who did not use NSAIDs other than naproxen or coxibs (p=0.17). <h3>Conclusions</h3> Patients with AS seemed at increased risk of developing IHD, but this effect could be attributed to their recent NSAID use. Although it cannot be excluded that NSAID use is (partly) a reflection of disease activity, rheumatologists should carefully balance the beneficial effects of NSAIDs and the increased risk of IHD. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1853
Abstract 3609: MGCD265, an orally active Met/VEGFR multitargeted kinase inhibitor in Phase II clinical development, potently inhibits clinically relevant Met mutants
Authors: Normand Beaulieu, Isabelle Dupont, Claire Bonfils, Marja Dubay, Hélène Ste-Croix, Lubo Isakovic, Stephen Claridge, Oscar Saavedra, Franck Raeppel, Stephane Raeppel, Michael Mannion, Arkadii Vaisburg, Jeffrey M. Besterman, Christiane R. Maroun
Journal: Cancer Research (2010)

Abstract MGCD265 is a multitargeted receptor tyrosine kinase inhibitor in Phase II clinical development, which inhibits the activation of regulators of cancer development and progression by targeting Met, the three members of the VEGFR family, Tie-2 and Ron. Met is a key player in the epithelial-mesenchymal transition (EMT) and Met deregulation is described in several types of cancer. The mechanisms involved in Met activation include co-expression of Met with its ligand HGF, overexpression of the Met protein, Met and/or HGF gene amplification or activating mutations. Originally found in hereditary papillary renal carcinoma (HPRCC), activating missense mutations in the kinase domain provided the first evidence that Met activation was causative of this disease. Mutations outside of the tyrosine kinase domain, such as those in the juxtamembrane and extracellular sema domains have also been analyzed, and found in NSCLC, SCLC, melanoma, head and neck cancer, mesothelioma and pancreatic cancer. For the clinical development of MGCD265, we demonstrated the ability of MGCD265 to inhibit clinically relevant Met mutants described in a variety of cancers, including HPRCC and NSCLC. In cell-based assays, MGCD265 inhibits the activation of Met kinase domain mutants (e.g. Y1230C) as well as mutants within the juxtamembrane region (e.g. R988C), and the extracellular domain (e.g. N375S) with nanomolar potency. This is of particular interest, as several kinase domain mutations confer resistance of Met to Met-selective agents such as PF-4217903. MGCD265 also inhibits signaling pathways activated downstream from Met mutants. The phosphorylation of Gab1 multisubstrate docking protein following the activation of Met mutants is inhibited by MGCD265 as is the ensuing activation of the Erk pathway. Furthermore, MGCD265 inhibits the motility of renal carcinoma cells expressing an extracellular domain Met mutant, and blocks tumor growth in a NSCLC cell line expressing a juxtamembrane domain Met mutant. These results, together with our previous findings, demonstrate that MGCD265 is particularly efficient at inhibiting tumor growth in animal models in which wild-type Met or Met mutants are active, suggesting that MGCD265 may particularly benefit patients with activated Met. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3609.
A2.40 Investigating IL-6 pathway signalling kinetics in peripheral blood single cell subsets with tocilizumab therapy in patients with early rheumatoid arthritis
Authors: L Ouboussad, C Wong, L Hunt, P Emery, MF McDermott, MH Buch
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Rheumatoid arthritis (RA) arises in individuals with a genetic predisposition, triggered by environmental influences, leading to dysfunctional immune responses. The importance of pro-inflammatory cytokines, such as TNF and IL-6, in RA is well recognised, and the successful use of biologic agents inhibiting their action is widely established. The study of the intracellular effect of cytokine ligation to their receptors is of interest in elucidating mechanisms of action and potentially response prediction. This project focuses on the IL-6 signalling pathway and its blockade, using tocilizumab (TCZ; IL-6 receptor monoclonal antibody) to (i) determine the relative roles of the 3 arms of the pathway (JAK-STAT but also, PI3K/Akt and MAPK/ERK) in T-cells, B-cells and monocytes; (ii) examine whether there is heterogeneity in the predominant IL-6 intracellular signalling pathway and whether this associates with response to TCZ (iii) the effect of TCZ therapy on intracellular pathways. <h3>Materials and methods</h3> Multiparameter phosflow cytometry method to identify phosphorylation intensities of transcription factor STAT3 and tyrosine kinases Akt and Erk that cover the entire IL-6 pathway is being undertaken. Twenty patients with treatment-naïve, early RA; 10 of whom are receiving TCZ monotherapy and 10 receiving combined methotrexate and TCZ have been recruited. Peripheral blood mononuclear cells (PBMCs) have been isolated at baseline, weeks 24 and 48 after treatment and cryopreserved. Healthy individual samples have been used as control. PBMC are either unstimulated, or stimulated with IL-6 or PMA, in order to activate the pathway. Median fluorescence intensity (MFI) is being measured using LSRII (BD Biosciences), and data are analysed using BD FACSDiva software. <h3>Results</h3> After adequate optimisation and using a gating strategy to identify immune cell subsets, including lymphocytes (T, B and NK cells) and monocytes (CD14 and CD16 subsets), the phosphorylation kinetics of p-STAT3, p-Akt, p-Erk1/2 are being monitored. Preliminary data suggest that there are differences in immune cell signalling between healthy individuals and RA patients. In addition, following stimulation, differences in the MFI have been observed in the cell subsets. The phosflow cytometry and data analyses will be completed shortly and presented as heat maps to illustrate baseline differences and changes following TCZ. <h3>Conclusions</h3> Comprehensive evaluation of IL-6 intracellular signalling within immune cells from RA patients will provide insights into disease pathophysiology and heterogeneity, TCZ drug mechanism of action and possibly prediction of outcome/response.