tbuckley/cabot-search huggingface dataset:
PTH-292 Malignant colorectal polyp outcomes – a four year cohort study
Authors: M Courtney, G Harris, L Newton, S Mills
Journal: Gut (2015)

<h3>Introduction</h3> The introduction of the bowel cancer screening programme (BCSP) has increased the detection of early colorectal cancers (CRC), including malignant polyps (MP). There remains, however, a lack of data on the ideal management of MPs. Formal operative bowel resection offers the sureity of extensive local resection (and assessment of loco-regional lymph nodes), but at the price of the attendant morbidity/mortality and, in cases of post-polypectomy resections, the specimen is often free of tumour. Endoscopic excision avoids that morbidity/mortality but at the potential price of local recurrence and undetected lymph node spread. The risk of residual disease after local or endoscopic resection based on histological factors is summarised in the ACPGBI position statement.<sup>1</sup>We aimed to assess outcomes of all patients treated for MPs in a single NHS trust. <h3>Method</h3> All T1 M0 cancers with a date of diagnosis between 01/04/10–31/03/14 were identified from a prospective, consecutive database of CRCs treated in the Trust, and the demographic, treatment and pathology data items exported. Electronic records of all subsequent endoscopic, radiological and histological tests were then searched to identify subsequent outcomes. Primary outcomes were disease-specific mortality, disease recurrence and metastases. <h3>Results</h3> Of 1238 CRCs ascertained, 130 (10.3%) fitted the inclusion criteria (T1 M0). Follow-up ranged from 3 to 58 months (median 34). Decision making in respect of local vs. formal surgical resection was based on multi-disciplinary discussion, informed by histopathological criteria where available, co-morbidities and patient preference. 34 (26.2%) underwent immediate formal resection, 68 (52.3%) were managed solely endoscopically, and 28 (21.5%) underwent endoscopic resection followed by completion colectomy (of which 24 had no residual disease). 10 patients died during follow-up, though none due to colorectal cancer or treatment. There was one case of liver metastases (who underwent local excision only, Kikuchi 2) and no local recurrences. <h3>Conclusion</h3> The low incidence of recurrence and metastases in this cohort reinforces that appropriate local resection of MPs does not negatively affect outcome at intermediate follow-up. The current ACPGBI position statement scoring system appears to appropriately select patients at low risk of residual disease. It is of note that there was no residual disease in 86% of formal resection specimens. There were missing histopathological criteria in many patients due to fragmentation of specimens and lack of synoptic reporting. Improving the proportion of en bloc local resections plus synoptic reporting may reduce the need for ‘unnecessary’ resections. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Williams JG, <i>et al</i>. Management of the malignant colorectal polyp: ACPGBI position statement. <i>Colorectal Dis.</i>2013;<b>15</b>(Suppl 2):1–38
Prognostic value of an extended tumor staging in a prospective study with detection of disseminated tumor cells in bone marrow, peritoneal cavity and lymph nodes in colorectal cancer
Authors: R. Steinert, M. Hantschick, M. Vieth, I. Gastinger, F. Kuehnel, H. Lippert, M. A. Reymond
Journal: Journal of Clinical Oncology (2005)

3539 Background: The traditional definition of localized and surgical resectable colorectal cancer (CRC) is challenged by the discovery of disseminated tumor cells in various body compartments. But the influence of minimal residual disease (MRD) on survival remains unclear. Methods: MRD was determined prospectively in 222 patients operated for colorectal tumors using immunohistochemistry with anti-pan-cytokeratin and Ber-EP4 antibodies. This is the first study with a simultaneous detection of cell dissemination in all possible compartments in a large patient cohort. Prognostic significance was determined in relation to 140 clinical and pathological data. In a median follow-up time of 44,6 months the main endpoint was disease free survival (DFS). Results: Out of 205 patients having undergone surgery for CRC, 67 (32,7%) died of CRC-related causes, 22 patients (10,7%) developed local recurrence. Presence of epithelial cells was detected in bone marrow in 135 of 205 patients (65,9%) and was not associated with tumor stage nor with poorer DFS. Presence of metastatic cells in peritoneal cavity are detectable in 50 of 194 patients (25,8%). They are associated with lymph node involvement (p<0,001), UICC stage and tumor invasion (p=0,001), CEA-level (p=0,003), tumor stenosis (p=0,004) and, in univariate analysis, with reduced DFS (p=0.006). Lymph nodes micrometastases were found in 50 of 107 (46,7%) UICC stage I or II patients, correlated with UICC stage (p=0.03), tumor invasion (p=0,025) tumor shape (p=0,002) and macroscopic tumor type (p=0,044), but not with DFS. Conclusions: Tumor cells disseminate into various body compartments throughout all stages of CRC. In about two-third of patients, tumor cells are left in the body after curative surgery. We have to memorize this fact for future adjuvant therapies. However, only the peritoneal tumor cells have an influence, but not an independent prognostic significance, in relation to established parameters. Thus, other factors such as the presence of a cellular metastatic phenotype and/or ineffective immunological response must play an important role in diagnosis and prognosis of MRD. No significant financial relationships to disclose.
Essential Thrombocytosis Patients Have At Diagnosis Prevalence Of CD8+ and CD45RO+CCR7- Lymphocytes and High Proportions Of Double Positive IL-17+/CD15+ Cells In The Marrow Cell Population
Authors: Mariola Sedzimirska, Aleksandra Klimczak, Emilia Jaskula, Dlubek Dorota, Andrzej Lange
Journal: Blood (2013)
Cathétériseurs en Chine: résultats de deux enquêtes nationales en 2007 et 2013
Authors: L. Heyries
Journal: Endoscopy (2016)

La Société Chinoise d’Endoscopie Digestive a mené 2 études observationnelles en 2007 et 2013 sur la CPRE. Les résultats donnent une idée de l’évolution de cette exploration.
Inhibition Of CXCR2 As a Therapeutic Strategy In AML and MDS
Authors: Carolina Schinke, Orsolya Giricz, Shanisha A. K. Gordon, Laura Barreyro, Tushar D. Bhagat, Andrea Pellagatti, Jacqueline Boultwood, Yiting Yu, Ulrich Steidl, Amit Verma
Journal: Blood (2013)
Abstract 42: Target inhibitory networks and drug response modeling
Authors: Uma Shankavaram, Kevin Camphausen
Journal: Clinical Cancer Research (2016)

Abstract Cancer is a complex disease caused by multiple factors, which hamper effective drug discovery. Drug combination or multi target agents provide an alternate way to effectively modify disease networks. Synergistic drug pairs have special potential for treatment since they allow a desired effect to be achieved with lower total dose of administered medicine and usually with fewer side effects. However, the major challenge has been the prediction of chemotherapeutic efficacy based on the biological profile of the tumor. Because of the lack of gene expression data treated with drug combinations, in this study, we present a computational approach to identify effective drug combinations by exploiting high throughput data. We constructed tissue specific network pharmacology based on large-scale screening data on drug treatment efficacies of 130 drugs under clinical and preclinical investigation and drug-target binding affinities. We evaluated CNS cancer subset and applied logic based network algorithm to predict effective drug combinations based on drug-target interactions and single drug sensitivity profiles. Cancer cell based target inhibition network analysis in two case studies using glioma cell lines, (U87 and U251) identified distinct cell line survival pathways (p &amp;lt; 0.001), including cell proliferation, adhesion and growth factor signaling. We estimated pairwise drug synergy scores for all the target genes and identified several synergistic pairs with potential clinical relevance. Target inhibition modeling allowed systematic exploration of functional interactions between drugs and their targets to maximally inhibit multiple survival pathways. Citation Format: Uma Shankavaram, Kevin Camphausen. Target inhibitory networks and drug response modeling. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr 42.
Burden of Nonsynonymous Mutations among TCGA Cancers and Candidate Immune Checkpoint Inhibitor Responses
Authors: Leandro M. Colli, Mitchell J. Machiela, Timothy A. Myers, Lea Jessop, Kai Yu, Stephen J. Chanock
Journal: Cancer Research (2016)

Immune checkpoint inhibitor treatment represents a promising approach toward treating cancer and has been shown to be effective in a subset of melanoma, non-small cell lung cancer (NSCLC), and kidney cancers. Recent studies have suggested that the number of nonsynonymous mutations (NsM) can be used to select melanoma and NSCLC patients most likely to benefit from checkpoint inhibitor treatment. It is hypothesized that a higher burden of NsM generates novel epitopes and gene products, detected by the immune system as foreign. We conducted an assessment of NsM across 7,757 tumor samples drawn from 26 cancers sequenced in the Cancer Genome Atlas (TCGA) Project to estimate the subset of cancers (both types and fractions thereof) that fit the profile suggested for melanoma and NSCLC. An additional independent set of 613 tumors drawn from 5 cancers were analyzed for replication. An analysis of the receiver operating characteristic curves of published data on checkpoint inhibitor response in melanoma and NSCLC data estimates a cutoff of 192 NsM with 74% sensitivity and 59.3% specificity to discriminate potential clinical benefit. Across the 7,757 samples of TCGA, 16.2% displayed an NsM count that exceeded the threshold of 192. It is notable that more than 30% of bladder, colon, gastric, and endometrial cancers have NsM counts above 192, which was also confirmed in melanoma and NSCLC. Our data could inform the prioritization of tumor types (and subtypes) for possible clinical trials to investigate further indications for effective use of immune checkpoint inhibitors, particularly in adult cancers. Cancer Res; 76(13); 3767-72. ©2016 AACR.
Abstract PR02: The diverse roles of long noncoding RNAs in the p53 tumor suppressor pathway
Authors: Jordan Bendor, Jesse Zamudio, Tyler Jacks, Nadva Dimitrova
Journal: Cancer Research (2016)

Abstract The p53 tumor suppressor is a transcription factor, which plays a central role in the cellular response to DNA damage and oncogenic stress. Using genetic approaches in the mouse as well as antisense technology, we have previously shown that the p53-regulated lncRNA, lincRNA-p21 activates the expression of its neighboring gene, the critical G1/S checkpoint mediator, p21. Mechanistically, we found that lincRNA-p21 localizes at its site of transcription, where it acts in cis to stabilize the binding of p53 and its transcriptional co-activator hnRNP-K at the promoter of p21. Importantly, using CRISPR-based approaches to modify the endogenous lincRNA-p21 locus in primary human fibroblasts, we show that the role of lincRNA-p21 in promoting p21 levels is conserved between mouse and human. To expand our understanding of the contribution of lncRNAs to the p53 tumor suppressor pathway, we have performed p53 ChIPseq and RNAseq under conditions of oncogenic stress and identified multiple previously uncharacterized lncRNAs that are regulated in a p53-dependent manner. One of them, lincRNA-Dhx15 is a novel lncRNA expressed from a bidirectional promoter shared with the RNA helicase Dhx15. LincRNA-Dhx15 is a direct target of p53 by virtue of multiple p53 response elements located in its first intron and appears to be preferentially expressed under conditions of senescence. We have generated a conditional knockout of lincRNA-Dhx15 in the mouse and found that absence of lincRNA-Dhx15 leads to impaired induction of senescence following prolonged exposure to DNA damage. Moreover, by gene expression profiling, we observed a downregulation of a subset of p53 target genes, suggesting that lincRNA-Dhx15 plays a global role in the p53 pathway. Surprisingly, we found that lincRNA-Dhx15 is exported to the cytoplasm and appears to promote the translational of p53 itself. The mechanistic basis for lincRNA-Dhx15 function is under active investigation. Altogether, these studies reveal that p53-regulated lncRNAs act through diverse mechanisms to add important layers of regulation to the p53 transcriptional network. Citation Format: Jordan Bendor, Jesse Zamudio, Tyler Jacks, Nadva Dimitrova. The diverse roles of long noncoding RNAs in the p53 tumor suppressor pathway. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr PR02.
Abstract IA20: Post-transcriptional regulation of metastatic progression
Authors: Sohail F. Tavazoie
Journal: Cancer Research (2015)

Abstract Post-transcriptional regulation represents an increasingly studied layer of gene expression control. In recent years, it has become increasingly evident that deregulation in post-transcriptional control mechanisms represents an important feature of the aggressive malignant phenotype. We have found that distinct cancers arising from various tissues such as the breast, skin, and the colon modulate unique tissue-specific sets of small non-coding RNAs (microRNAs) as they acquire a highly metastatic phenotype. We have used these microRNAs as molecule probes to better understand the molecular and cellular biology underlying metastatic progression. These studies have revealed surprising pathways and mechanisms utilized by cancer cells to colonize metastatic microenvironments. We find that while distinct tissues such as breast and melanoma might modulate distinct miRNAs and downstream target genes, the cellular phenotypes impacted by these pathways en route to metastatic colonization can be similar. Importantly, clinical association studies using human specimens support the roles for these miRNAs and their downstream effectors in metastatic progression. These basic studies into the molecular and cellular biology of metastatic progression have revealed key target genes whose pharmacological modulation in proof-of-concept pre-clinical studies have revealed robust therapeutic effects. Citation Format: Sohail F. Tavazoie. Post-transcriptional regulation of metastatic progression. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr IA20.
Lack of Measles Transmission to Susceptible Contacts from a Health Care Worker with Probable Secondary Vaccine Failure — Maricopa County, Arizona, 2015
Authors: Jefferson Jones, Ron Klein, Saskia Popescu, Karen Rose, Melissa Kretschmer, Alice Carrigan, Felicia Trembath, Lia Koski, Karen Zabel, Scott Ostdiek, Paula Rowell-Kinnard, Esther Munoz, Rebecca Sunenshine, Tammy Sylvester
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

On January 23, 2015, the Maricopa County Department of Public Health (MCDPH) was notified of a suspected measles case in a nurse, a woman aged 48 years. On January 11, the nurse had contact with a patient with laboratory-confirmed measles associated with the Disneyland theme park-related outbreak in California. On January 21, she developed a fever (103°F [39.4°C]), on January 23 she experienced cough and coryza, and on January 24, she developed a rash. The patient was instructed to isolate herself at home. On January 26, serum, a nasopharyngeal swab, and a urine specimen were collected. The following day, measles infection was diagnosed by real time reverse transcription polymerase chain reaction testing of the nasopharyngeal swab and urine specimen and by detection of measles-specific immunoglobulin (Ig)M and IgG in serum by enzyme-linked immunosorbent assay. Because of her symptoms and laboratory results, the patient was considered to be infectious.
Risks and Benefits of Hormonal Agents in Pregnancy
Authors: A F Kohrman, L A Jones, H A Bern
Journal: New England Journal of Medicine (1976)

Concern over the possible teratogenic effects of the hormone 17alpha -hydroxyprogesterone caproate (17alpha OHP-C) when given intrapartum to the mother and the possible effects on the cervix and vagina in later life, was voiced in response to a published report, and advocacy of use of this hormone for the prevention of early abortion questioned. In response, the authors share their concern over possible long-term carcinogenic effects as well as possible effects on the hypothalamic-pituitary-gonadal axis, the mammary apparatus, the male genitalia, and psychosexual behavior.
Perceptual changes with bupropion, a novel antidepressant
Authors: R E Becker, R L Dufresne
Journal: American Journal of Psychiatry (1982)

The authors assessed perceptual changes in 12 depressed patients treated wih bupropion, 12 patients given other antidepressants, and 12 drug-free controls. Bupropion was associated with vivid dreaming and changes in attention, memory, and perception. which may have contributed to its therapeutic effectiveness.
Soundings: The New Ethics
Authors: Trisha Greenhalgh
Journal: BMJ (2004)

Mornings tend to drag for us academics, so let me tell you about a computer game that will help you while away the hours till lunch.

There's a new system for applying for research ethical approval (www.corec.org.uk). Like most things these days apart from registering births or deaths (though I'm told the latter is coming), you are now encouraged to do it all online.

Start by scrutinising the New Operational Procedures (= how to fill the form in and where to send it). This should take you to coffee time. You'll find a three page algorithm showing which parts of the form to send in which direction. Make sure your research administrator (you should have one) prints it out and glues it to his or her wall. The glossary of terms helpfully sets out the difference between an Amendment, an Administrative Amendment, and a Substantial Amendment (keep these handy for when you get to the resubmit stage). It also explains important ethical terms such as Regulations, EU Directive Studies, and Site Specific Assessment. (For minor terms such as equipoise, consent, distress, harm, conflict of interest, and probity, see the Oxford English Dictionary.)

Next, click your way to the application itself. It comes in four parts. Parts A, B, and C (totalling 57 pages) can be filled in online, but for part D you need to install a bespoke piece of software. Play about for an hour or so, cutting and pasting information from your research grant application into the boxes on the web page. For closed questions (eg, “will informed consent be obtained?”) it should be obvious which radio button to click. Responses to open questions will be carefully screened for sarcasm, so resist the temptation to say, “I thought I'd answered that one two pages ago” or “how many minutes do you think it takes to obtain 5 ml of blood?”

On the final page (you should be hungry by now), you will be asked to supply the dates of the study in DD/MM/YYYY format. Try 31/07/2004, which it will autocorrect to 07/31/2004. Then press “save.” The pop-up box will tell you it can't save your form because there are not 31 months in a year, nor can you log out until you've sorted out your mistake. Re-insert the date in the required format. Watch it autocorrect to the wrong format. Attempt to save. Etc.

Game over. Press Ctrl-Alt-Delete and go for lunch.
An empirical study of emergency commitment
Authors: L R Faulkner, B H McFarland, J D Bloom
Journal: American Journal of Psychiatry (1989)

The authors examine the emergency commitment process in one Oregon county and present data that document the impact of a local detention facility. The study reconfirms the dependence of commitment processes on the mental health system in which they occur, illustrates the relative inability of specific laws to determine the actual nature of commitment processes, provides support for the concept of community care for the people involved, and points to the need for additional research to clarify the effects of commitment procedures.
Enteropathy-associated T-cell lymphoma: involvement of the gastrointestinal tract from the duodenum to the rectum
Authors: Yusuf Demir, Şehmus Ölmez, Erdem Sürücü, Cengiz Demir, Funda Şenköy, İrfan Bayram
Journal: Endoscopy (2015)

Enteropathy-associated T-cell lymphoma (EATL) is a rare type of non-Hodgkin's lymphoma that is commonly associated with celiac disease. The disease is very aggressive with a poor prognosis, and no standardized treatment protocol has been established [1]. An early diagnosis and effective therapy may not be achieved because of the nonspecific clinical and endoscopic findings [2]. The radiologic features of the disease include wall thickening, ulceration, and perforation of the jejunum [3]. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography is a useful tool for the staging, management, and prognostication of T-cell lymphoma [4]. Here, we present a unique case of EATL with diffuse involvement of the intestine and colon.
A profile of clients referred for psychiatric evaluation for Social Security Disability Income and Supplemental Security Income: implications for psychiatry
Authors: S Okpaku
Journal: American Journal of Psychiatry (1985)

A study of the psychiatric evaluations of 248 consecutive clients whose cases were in the process of adjudication for approval or renewal of Supplemental Security Income and/or Social Security Disability Income in 1982 and 1983 showed an overrepresentation of individuals with chronic moderate to severe psychiatric impairment. The author suggests that the criteria and guidelines for eligibility for these two programs are too stringent for individuals with psychiatric impairment and that some of these individuals are unable to provide information necessary to build a proper case for disability because of their psychopathology. The implications for psychiatrists, other mental health professionals, and social policy planners are discussed.