tbuckley/cabot-search huggingface dataset:
Abstract P3-03-10: Pre-operative lymphoscintigraphy for sentinel lymph node localisation: Is it necessary?
Authors: SL Clark, D Yilmaz, K Arun, S Javadzadeh, S Saeed, MZ Ullah
Journal: Cancer Research (2019)

Abstract Introduction Sentinel lymph node biopsy (SLNB) has replaced lymph node clearance for staging of the axilla in patients with early invasive breast cancer and no evidence of lymph node involvement on ultrasound or needle biopsy. It is recommended that a dual technique, using isotope and blue dye, is used to locate the sentinel lymph node (SLN) intra-operatively. Often, at the time of radioisotope injection, a lymphoscintigram (nuclear medicine scan) is obtained to demonstrate the 'hot' sentinel lymph node with or without skin marking of its anatomical position. Performing a lymphoscintigram adds time and cost to the localisation process. In our centre, this investigation costs £899-999 (˜US $1180-1300). Aims The aim of this study is to find out whether obtaining a pre-operative lymphoscintigram aids the surgeon in the localisation of the SLN or affects the number of sentinel lymph nodes biopsied in the axillary staging of patients with early invasive breast cancer. Methods We carried out a retrospective study of patients who underwent SLNB for breast cancer in our hospital Trust between March 2012 and November 2017. We identified those patients who had a lymphoscintigram performed pre-operatively for SLN localisation. We recorded the number of SLNs identified on imaging and compared this with the number of SLNs biopsied during the operation. Results 349 patients underwent 354 SLNBs during the study period. One patient was male, the remainders were female. The mean age of patients was 57.2 years (range 25 to 98 years). In 295 (83.3%) cases, a lymphoscintigram was obtained prior to SLNB for node localisation, and 268 (90.8%) of these scans were able to identify one or more SLNs. In 173 (58.6%) scans, a single SLN was identified. In 27 (9.1%) scans it was either unclear how many SLNs were demonstrated or no SLNs were seen (16/295 no SLN identified, 11/295 unclear how many SLNs). In 102 (34.6%) cases, the number of SLNs biopsied matched the number of SLNs identified on imaging. Of those that did not match, 76.2% had more and 15.0% fewer SLNs excised than shown on imaging. In 8.8% it was unknown if the number of SLNs matched that seen on imaging due to lack of histopathology results. Conclusion Lymphoscintigraphy for SLN localisation is costly and time consuming. In a high proportion of cases, number of SLNs identified on imaging does not match the number biopsied and thus, we suggest, that it is not required prior to SLNB and should be removed from practice. Citation Format: Clark SL, Yilmaz D, Arun K, Javadzadeh S, Saeed S, Ullah MZ. Pre-operative lymphoscintigraphy for sentinel lymph node localisation: Is it necessary? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-10.
Use of the novel BougieCap in the treatment of esophageal peptic stricture
Authors: João Cortez-Pinto, Susana Mão de Ferro, António Dias Pereira
Journal: Endoscopy (2019)

Various methods are available for the endoscopic treatment of benign strictures in the upper gastrointestinal tract. The most common is the sequential use of Savary-Gillard bougies after passing a guidewire through the stricture [1]. The main problem with this method is the lack of direct visual control of the bougienage procedure [2]. BougieCaps (Ovesco Endoscopy AG, Tübingen, Germany) are single-use caps of different sizes that can be attached to an endoscope. Bougienage is carried out by advancing the endoscope through the stenosis while allowing good visualization of the surrounding tissue [3].
Novel Associations Between Mutations, Prognostic and Clinical Parameters in Untreated Progressive CLL: Data from E1912, a Randomized Phase III Study of the ECOG-ACRIN Cancer Research Group
Authors: Esteban Braggio, Victoria X Wang, Santiago Garcia, Laura Ann Bruins, Connie Lesnick, Jacqueline C. Barrientos, Susan M. O'Brien, Martin S. Tallman, Rafael Fonseca, Neil E. Kay, Tait D. Shanafelt
Journal: Blood (2016)
Abstract P3-10-17: mRNA expression of HER2 by PCR as a strong predictor of pathologic response to neoadjuvant antiHER2 therapy
Authors: A Gasol Cudós, S Morales Murillo, J Veas Rodriguez, A Velasco Sánchez, A Serrate López, J Melé Olivé, C Canosa Morales
Journal: Cancer Research (2019)

Abstract Background: Pathologic response to neoadjuvant therapy is the most important prognostic factor so new agents should aim to improve it. HER2 expression in breast cancer provides prognostic and predictive information of response to antiHER2 therapy. The quantification of HER2 expression by mRNA is one of the most potent markers of cellular dependence to HER2 pathway. Methods: From a series of 160 patients with early or locally advanced HER2 positive breast cancer who received neoadjuvant treatment with chemotherapy and antiHER2 drugs, mRNA expression of HER2 was analyzed in 69 specimens and it was correlated to pathologic complete response (pCR). Results: Median age was of 52.5 years (29-86), tumor size of 33mm (10-111), 39 (53%) patients had nodal involvement. Median ki67 expression was of 45% (17-80), 28 (38%) tumors were estrogen receptor (ER) positive and 46 (62%) negative. We also analyze the expression of tumor-infiltrating-lymphocytes (TILs) by immunohistochemistry in 43 samples because their expression is also a strong predictive of pathologic response. A total of 31/69 patients (45%) achieved a pCR with a median of mRNA expression of 7,55 (3,8 – 11) in comparison with 2.03 (1,2 -2,8) in patients without pCR (p: 0,002). In the univariable analysis, variables correlated to pCR were estrogen receptor=0 (OR 0,186 IC 95% 0,063-0,549, p: 0,002), mRNA (OR 5,689 IC 95% 1,854-17,452, p: 0,002) and TILs (OR 15,167 IC 95% 3,223-71,38, p: 0,001) and in the multivariable analysis, TILs and mRNA expression were found to be independent predictive factors for pCR. The quantification of HER2 by mRNA obtained an impressive response specially in ER negative patients with a rate of pCR of 100% in samples of mRNA expression upper of 3,6 and ER negative. However, patients with mRNA expression lower than 3,6 with a pCR rate of 32%, could reach to an 80% rate if they had high TILs expression. Conclusions: Quantification of HER2 expression by mRNA is a strong predictive factor of pCR (OR 5,689); achieving a 100% pCR in ER negative tumors. TILs are also a predictive factor for pCR (OR 15,167) and its combination with mRNA expression could improve pCR rates; thus, patients with mRNA expression lower than 3,6, if they had a higher TILs expression could reach to an 80% pCR. Citation Format: Gasol Cudós A, Morales Murillo S, Veas Rodriguez J, Velasco Sánchez A, Serrate López A, Melé Olivé J, Canosa Morales C. mRNA expression of HER2 by PCR as a strong predictor of pathologic response to neoadjuvant antiHER2 therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-17.
Abstract P2-10-33: Mitotic Component of Grade Can Distinguish Breast Cancer Patients at Greatest Risk of Local Relapse
Authors: SJ Done, NA Miller, Shi W Wei, M Pintilie, DR McCready, F-F Liu, A Fyles
Journal: Cancer Research (2012)

Abstract Background: With the recent recognition of many different molecular subtypes of breast cancer a desire to more specifically categorize tumors to allow tailoring of treatment to individual patients has developed. This has largely involved the development of molecular tests rather than the re-examination of current pathologic criteria. We wanted to evaluate standard pathologic features to determine their ability to predict for local recurrence. Materials and Methods: Slides were retrieved for review from 280 of 769 women who had participated in a trial of tamoxifen with or without breast irradiation between December 1992 and June 2000 and for whom outcome data up to 18 years was available. All women were 50 years of age or older at the time of enrollment and had T1 or T2 node negative breast cancer. The cases for which slides were obtained were representative of the whole group. The slides were reviewed by two breast pathologists (SJD and NAM). Several features were evaluated; modified Nottingham histologic grade and its components- degree of tubule formation, nuclear pleomorphism and mitotic count. Mitotic component of grade was calibrated to the microscopic field size used. The presence of lymphatic/vascular space invasion was also scored. A statistical analysis was performed to relate these pathologic features to local recurrence at up to 18 years. Results: The strongest predictor of local recurrence was the mitotic component of the Nottingham histologic grade with 5.7% for mitotic score 1/3 (n = 200), 19.6% for mitotic score 2/3 (n = 37) and 19.8% for mitotic score 3/3 (n = 43)(Gray's p-value = 0.0021). Overall grade was also able to predict for local recurrence with 2.6% for Grade 1 (n = 49), 10.6% for Grade 2 (n = 162) and 17.9% for Grade 3 (n = 71)(Gray's p-value=0.026). However, neither architecture (0% vs. 9.5% vs. 9.8%, Gray's p-value=0.74) nor degree of nuclear pleomorphism (0% vs. 7.9% vs. 11.5%, Gray's p-value=0.37), the other components of histologic grade, showed a statistically significant difference for recurrence. The presence or absence of endothelial lined space invasion was also found to be not statistically different (9.3% vs. 13%, Gray's p-value=0.55). Conclusion: Within this cohort of tamoxifen treated T1 and T2 breast cancer patients 50 years of age or older, mitotic index could stratify women into groups with high and low risk of recurrence. If validated this may be a useful way of allocating patients to different treatment groups. Additional validation studies are planned on similar groups of patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-33.
Abstract 13287: Anti-Apoptotic BAG3 Gene in Tako-Tsubo Cardiomyopathy
Authors: Rodolfo Citro, Margot De Marco, Morena D’Avenia, Antonia Falco, Marco Mirra, Roberta Giudice, Angelo Silverio, Costantina Prota, Eduardo Bossone, Federico Piscione, Maria Caterina Turco
Journal: Circulation (2012)

Background and aim: Tako-tsubo cardiomyopathy (TTC) is a stress related acute cardiac condition characterized by transient myocardial stunning inducing left ventricular systolic dysfunction in abse...
What options are available as a portfolio GP?
Authors: Caroline Elton
Journal: BMJ (2016)

Dear Caroline

As half of medical students look destined to end up in general practice, what variety is available in this specialty? I’ve heard the term “portfolio GP” mentioned but I’m not sure what it means or how GPs manage other interests with their clinical work.

Anna Watkinson-Powell, final year medical school, University of Sheffield

Caroline replies . . .

Although there is the potential for variety in all specialties, general practice is the specialty where it is most straightforward to establish a varied career. Firstly, there is huge variety in the nature of the work depending on the sort of GP practice you join. For example, a GP in a small rural practice will have different patients and interactions with their colleagues compared to a GP who works in a larger inner city primary care centre, where there may be as many …
An unexpected finding in a randomised controlled trial
Authors: Peter Wilmshurst
Journal: BMJ (2013)

My favourite presentation at Evidence Live (www.evidencelive.org/)—the conference on evidence based medicine—was on the FEAST trial, which was a multicentre randomised controlled trial of fluid replacement in young children with severe febrile illness (most caused by malaria) in east Africa.1

This is an important topic because many young children die every day from dehydration secondary to febrile illnesses, particularly in developing countries.

The interventions that were compared, namely intravenous infusion of fluids, were clinically applicable …
Abstract P6-20-10: Role of GPR110 in breast cancer
Authors: R Bhat, L Qin, C De Angelis, D Sahay, D Bhargava, C Creighton, P Yadav, S Yazdanfard, A Alrawi, V Yadav, S Vasaikar, S Nanda, V Sethunath, X Fu, B Zhang, V Narkar, R Schiff, M Trivedi
Journal: Cancer Research (2019)

Abstract Our long-term goal is to discover adhesion GPCR targets in breast cancer. Our previous studies have found GPR110 to be overexpressed in tumorigenic cell population as well as in anti-HER2 drug-resistant derivatives of HER2+ breast cancer cells. In subsequent studies, we found that GPR110 knockdown inhibited anchorage-independent cell growth, mammosphere formation, and invasion/migration of HER2+ breast cancer cells. Conversely, overexpression of GPR110 by lentiviral delivery of cDNA enhanced anchorage-independent cell growth, mammosphere formation, and invasion/migration in HER2+ breast cancer cells. In addition, GPR110 overexpression led to increase in the % of Aldefluor-positive tumorigenic cell population, further emphasizing the role of GPR110 as a mediator of tumorigenesis in addition to the metastatic processes in HER2+ breast cancer. Among various subtypes of breast cancer, GPR110 expression was higher in HER2+ and basal subtypes, most of which are triple-negative (negative for ER, PR, and HER2), compared to luminal A and B subtypes. GPR110 was either gene amplified or upregulated in 4% of all breast cancers based on the publicly available TCGA dataset. GPR110 overexpression predicted poorer recurrence-free survival in triple-negative breast cancer. Furthermore, GPR110 was overexpressed in brain metastatic lesions compared to mammary tumors in patient-derived xenograft models of triple-negative breast cancer (WHIM2 and WHIM30). Knocking down GPR110 reduced anchorage-dependent and -independent cell growth, mammosphere formation, and invasion/migration of triple-negative breast cancer cells. Overall, our results suggest that GPR110 may be a potential drug target in HER2+ and triple-negative breast cancer. Drug discovery efforts to identify GPR110 antagonists will provide useful pharmacological tools for validating GPR110 as a drug target in breast cancer. Since GPR110 is also overexpressed in various other types of cancer, understanding the mechanism of GPR110 upregulation and signaling in cancer is an important future direction. This work was supported by the Department of Defense Grants W81XWH-14-1-0340 and W81XWH-14-1-0341 to Drs. Trivedi and Schiff, respectively. Citation Format: Bhat R, Qin L, De Angelis C, Sahay D, Bhargava D, Creighton C, Yadav P, Yazdanfard S, Alrawi A, Yadav V, Vasaikar S, Nanda S, Sethunath V, Fu X, Zhang B, Narkar V, Schiff R, Trivedi M. Role of GPR110 in breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-20-10.
Abstract SY31-03: Global signaling mechanisms that regulate autophagy
Authors: Caroline Yi, Junying Yuan
Journal: Cancer Research (2010)

Abstract Apoptosis is an evolutionally conserved cellular suicide mechanism that can be activated in response to a variety of stressful stimuli. Increasing evidence suggests that apoptotic regulation relies on specialized cell death signaling pathways and also integrates diverse signals from additional regulatory circuits, including those of cellular metabolism. Cell metabolism is exquisitely linked to multiple aspects of cell physiology relevant for cancer development, including cell proliferation, growth, and death. However, the mechanism by which cellular metabolism controls apoptotic sensitivity is unknown. We conducted a genome-wide RNA interference screen to systematically identify regulators of apoptosis induced by DNA damage in Drosophila melanogaster cells. This screen identified 47 double- stranded RNAs that target a functionally diverse set of genes, including several with a known function in promoting cell death. Further characterization uncovers 10 genes that influence caspase activation upon the removal of Drosophila inhibitor of apoptosis 1 (DIAP1). This set includes the Drosophila initiator caspase Dronc and, surprisingly, several metabolic regulators, and an N-acetyltransferase, ARD1. Importantly, several of these genes show functional conservation in regulating apoptosis in mammalian cells. Our data suggest a previously unappreciated fundamental connection between various cellular processes and caspase-dependent cell death. We have further explored the functional role and the mechanism by which ARD1 regulates apoptotic sensitivity in mammalian cells. We found that a reduction of N-alpha-acetylation mediated by ARD1 leads to inhibit apoptosis by blocking the interaction of a caspase with its activating complex. We further demonstrate the levels of protein N-alpha-acetylation is controlled by the availability of acetyl-CoA, a key intermediate metabolite. Our study provides a mechanistic link between cellular metabolism and apoptotic sensitivity and suggests that targeting the mechanism of protein N-alpha-acetylation may provide a new therapeutic approach for anti-cancer drug development. Citation Format: Caroline Yi, Junying Yuan. Global signaling mechanisms that regulate autophagy [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY31-03
Lumboperitoneal shunt: a foreign body detected in the small bowel by capsule endoscopy
Authors: Alejandro Pérez Fernández, José Francisco Sánchez Melgarejo, José María Rubio Mateos, María Josefa Sánchez Fernández, Silvia Chacón Martínez, Pilar Esteban Delgado, Enrique Pérez-Cuadrado Martínez
Journal: Endoscopy (2019)

Ventriculoperitoneal or lumboperitoneal shunts have a high rate of complications (23.8 %) [1], of which gastrointestinal complications account for 10 % – 30 % [2]. Small-bowel perforation secondary to ventriculoperitoneal shunt is reported in 0.1 % – 1 % of cases [3], with a 15 % risk of mortality [4]. Infection and chronic inflammation can lead to perforation of the bowel [2] [4], and acute traumatic or foreign body-type allergic reaction to the tubing material has been implicated in some cases [4]. Patients present asymptomatically, or with abdominal pain, diarrhea, shunt dysfunction, fever, leukocytosis or seizures [4]. The condition often causes peritonitis and other complications such as meningitis, which can be fatal if unrecognized [4], and which may require surgical, endoscopic, or a combination of surgical and endoscopic management [5].
Abstract ES4-1: Partial breast irradiation: Efficacy and patient selection
Authors: C Coles
Journal: Cancer Research (2019)

Abstract Partial breast irradiation is an attractive option for patients and clinicians as a smaller region of the breast is irradiated in (usually) a shorter time period compared with whole breast radiation therapy (RT). The hypothesis for this approach is that a smaller irradiated volume is likely to translate into decreased toxicity, whilst maintaining good local control and survival (efficacy). This educational lecture will examine in detail the efficacy of the four “modern” large, randomised partial breast RT trials that have been published in the last 5 years. These include the ELIOT, Targit-A, GEC-ESTRO and IMPORT LOW studies1-4. In addition, the eligibility criteria and baseline characteristics of recruited patients will be considered for each trial in the context of ipsilateral breast tumour relapse rates. Current national and international guidelines regarding patient selection for partial breast RT will also be discussed. References: 1.Veronesi U et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013 Dec;14(13):1269-77. 2.Vaidya JS et al; TARGIT trialists' group. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet. 2014 Feb 15;383(9917):603-13. 3.Strnad V et al; Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet. 2016 Jan 16;387(10015):229-38. 4.Coles CE et al; IMPORT Trialists. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2017 Sep 9;390(10099):1048-1060. Citation Format: Coles C. Partial breast irradiation: Efficacy and patient selection [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr ES4-1.
Abstract 16836: Ttc39b Deficiency Attenuates Atherosclerosis and Hepatic Steatosis Through Lxrα Dependent Manner
Authors: Masahiro Koseki, Joanne Heish, Matthew M Molusky, Emi Yakushiji, Marit Westerterp, Ikuyo Ichi, Sandra Abramowicz, Liana Tascau, Carrie B Welch, Shunichi Takiguchi, Jahangir Iqbal, Yasushi Sakata, Shizuya Yamashita, Mahmood M Hussain, Daniel J Rader, Alan R Tall
Journal: Circulation (2016)

Introduction: TTC39B was identified in genome wide association studies as a novel gene influencing HDL-cholesterol (HDL-C) levels. Hypothesis: We assessed the hypothesis that TTC39B might have a ro...
Clearing the Air. A Guide for Action on Tobacco
Journal: Thorax (1991)

Although we agree with most of the review, we would disagree with their comments on hypoxaemia.They state that absence ofhypoxaemia in vocal cord dysfunction helps to differentiate this condition from acute asthma.We have seen two cases ourselves' where hypoxaemia is a feature of vocal cord dysfunction.In one case the hypoxaemia (arterial oxygen tension Pao2) 79 mm Hg with 100%