tbuckley/cabot-search huggingface dataset:
P220 Role Of Ebus-tbna In The Diagnosis Of Primary And Relapsing Haematological Malignancy
Authors: R. Thakrar, G. Hardavella, J. Brown, L. Succony, M. Falzon, E. Borg, V. Jeebun, M. Munnavar, S. Janes, N. Navani
Journal: Thorax (2014)

<h3>Introduction</h3> Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) has been embraced as a breakthrough in the diagnosis and mediastinal staging of lung cancer. However, its utility in determining a diagnosis of lymphoma is not well defined, and is currently not recommended by the British Thoracic Society. <h3>Aim</h3> Evaluate the role of EBUS-TBNA in the diagnosis and subtyping of haematological malignancies. <h3>Method</h3> Patients referred with mediastinal lymphadenopathy for EBUS-TBNA in whom lymphoma was suspected, were identified retrospectively in 3 tertiary centres in the UK between 2008 and 2013. EBUS was performed using a linear array ultrasonic bronchoscope and specimens taken with a 21 or 22 gauge needle. The diagnostic accuracy, avoidance of mediastinoscopy and surgical biopsy in cases of primary and relapsing haematological malignancy was recorded. Where EBUS-TBNA was negative, patients subsequently underwent surgical biopsy or clinical and radiological surveillance. <h3>Results</h3> Twenty-four patients (10 female and 14 male) with a mean age of 55.5 years underwent EBUS-TBNA for evaluation of mediastinal lymphadenopathy. Clinical and radiological diagnosis was of either, isolated mediastinal lymphadenopathy of unknown cause (n = 15) or suspected mediastinal recurrence of lymphoma (n = 8). Five patients (62.5%) were found to have a relapse of their haematological malignancy, whilst a new diagnosis of lymphoma was made in 11 cases (73.3%) where the presentation was of isolated mediastinal lymphadenopathy. One patient in this group was found to have tuberculosis. Tissue obtained from nodal aspiration was sufficient to subtype the disease in detail in 14 patients with immunohistochemistry. Overall, 17 patients (70%) were prevented from having mediastinoscopy and other biopsies, and the diagnostic accuracy and sensitivity of EBUS-TBNA in primary and relapsing lymphoma was 74%. <h3>Conclusion</h3> EBUS-TBNA is a safe and important approach to mediastinal lymphadenopathy in suspected lymphoma, whereby detection of either primary or relapsing haematological malignancy prevents need for other more invasive biopsies.
Extensive squamous metaplasia in the rectum stained with a Lugol’s solution in patient with ulcerative colitis and primary sclerosing cholangitis
Authors: Edyta Zagórowicz, Andrzej Pawełas, Anna Rawa-Gołębiewska, Janina Orłowska
Journal: Endoscopy (2014)

A case of extensive squamous metaplasia in a patient with longstanding ulcerative colitis and primary sclerosing cholangitis is presented. The patient was a 52-year-old man with a 20-year history of pancolitis who was referred for surveillance colonoscopy. No suspicious lesions had been found on previous examinations. Inspection of the rectum revealed a whitish epithelium lining the distal portion of the bowel, which was almost complete in circumferential extent and approximately 2 cm long at its maximum extent ([Fig. 1]). Lugol's solution, known for its interaction with glycogen in a squamous epithelium, was used as a stain. An irregular border between the rectal mucosa and the metaplastic epithelium was clearly demarcated, and details of the surface of the latter could be easily observed ([Fig. 2]). As expected, histopathology confirmed the presence of squamous epithelium in the rectum.
Tips for a Physician in Getting the Right Job, Part XIX
Authors: Jay Harolds
Journal: Clinical Nuclear Medicine (2014)

It is very helpful for physicians searching for a job to know a little about employment contracts. This article summarizes some important principles about contracts and some of their clauses. The article also emphasizes the importance of having the understandings regarding employment put in a formal written contract. This article may help the candidate avoid certain difficulties and may help in contract negotiations. However, this article is not a substitute for legal advice, and all physicians should consult a lawyer before signing an employment contract.
Relation between Aortic Atherosclerosis and the Use of Cigarettes and Alcohol
Authors: David L. Sackett, Robert W. Gibson, Irwin D. J. Bross, John W. Pickren
Journal: New England Journal of Medicine (1968)

Examination of 1019 consecutively autopsied white patients who underwent standardized interviews before death, demonstrated no statistically significant relation between aortic atherosclerosis and the use of alcohol. However, a graded and statistically significant increase in the severity of aortic atherosclerosis was found with increasing use of cigarettes measured by both intensity (packages per day) and duration (number of years of smoking). Selective biases in the formation of the study population and faulty collection of historical data have, we believe, been excluded. These findings thus confirm and augment earlier studies of a relation between aortic and coronary atherosclerosis and cigarette smoking.
Abstract LB-359: Inhibition of DNA repair by the dual PI3K/mTOR inhibitor NVP-BEZ235 as a novel radiosensitization strategy for glioblastoma.
Authors: Carlos Gil Del Alcazar, Molly Gillam, Nozomi Tomimatsu, Xiaohuan Gao, Bipasha Mukherjee, Sandeep Burma
Journal: Cancer Research (2013)

Abstract Glioblastomas (GBM) are deadly brain tumors with extremely poor prognosis. The standard of care for GBM is tumor resection followed by treatment with ionizing radiation (IR) and the DNA alkylating agent temozolomide. As GBMs are highly radioresistant, it is crucial to identify effective radiosensitizers for improving therapeutic outcome. We find that NVP-BEZ235, a dual PI3K/mTOR inhibitor that is in clinical trials, potently inhibits both ATM and DNA-PKcs, the two major kinases that respond to IR-induced DNA double-strand breaks (DSBs). Consequently, this drug blocks non-homologous end joining (NHEJ) as well as homologous recombination (HR), the two major pathways of DSB repair. We find that low concentrations of NVP-BEZ235 (100 nM) can block DSB repair in a panel of human GBM lines resulting in significant radiosensitization. This radiosensitizing effect is more potent than that seen with much higher concentrations (10 μm) of current inhibitors of DNA-PKcs or ATM that are being optimized for clinical testing. In order to examine the effects of NVP-BEZ235 in vivo, we sub-cutaneously injected mice with radioresistant U87 glioma cells ectopically expressing EGFRvIII and treated with clinically-relevant doses of the drug. We find that NVP-BEZ235 blocks the activation of both DNA-PKcs and ATM in irradiated tumors resulting in significant attenuation of DSB repair. Tumors treated with a combination of IR and NVP-BEZ235 exhibit elevated DSBs and reduced Ki67 positivity compared to tumors treated with only IR or NVP-BEZ235. Consequently, a combination of IR and NVP-BEZ235 results in dramatic inhibition of tumor growth, in contrast to almost no inhibition with either treatment modality alone. Finally, we established that NVP-BEZ235 can cross the blood-brain barrier and therefore examined its effectiveness in an orthotopic brain tumor model. We find that NVP-BEZ235 given with IR can attenuate the growth of intracranial tumors generated from U87-EGFRvIII cells, thereby extending survival of tumor-bearing mice. Importantly, NVP-BEZ235 also sensitizes subcutaneous and intracranial tumors to temozolomide by attenuating the repair of secondary (replication-associated) DSBs that are generated upon temozolomide treatment. In sum, this study provides support for the potential use of NVP-BEZ235 as a radio- and chemo-sensitizer for improving the outcome of GBM therapy. Citation Format: Carlos Gil Del Alcazar, Molly Gillam, Nozomi Tomimatsu, Xiaohuan Gao, Bipasha Mukherjee, Sandeep Burma. Inhibition of DNA repair by the dual PI3K/mTOR inhibitor NVP-BEZ235 as a novel radiosensitization strategy for glioblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-359. doi:10.1158/1538-7445.AM2013-LB-359
AT-49 * SAFETY EVALUATION OF HIGH-DOSE BCNU-LOADED BIODEGRADABLE IMPLANTS IN CHINESE PATIENTS WITH RECURRENT MALIGNANT GLIOMAS
Authors: K. Sai, M.-g. Zhong, Z.-p. Chen
Journal: Neuro-Oncology (2014)

OBJECTIVES: Malignant gliomas are common primary brain tumors with dismal prognosis. The blood-brain barrier and unacceptable systemic toxicity limit the employment of chemotherapeutic agents. BCNU-impregnated biodegradable polymers (Gliadel®) have been demonstrated to prolong the survival of patients with malignant gliomas. Until now, no biodegradable drug delivery system has been commercially available in China. In the present study, we evaluated the safety of implants with high-dose BCNU in Chinese patients with recurrent malignant gliomas. PATIENTS AND METHODS: Adults with supratentorial recurrent malignant glioma were eligible. High-dose BCNU-loaded PLGA implants (20 mg of BCNU in each implant) were placed in the debulking cavity. The implants were investigated by a classical 3 + 3 design. Four levels of BCNU, up to 12 implants, were evaluated. Pharmacokinetic sampling was performed. The toxicity of the implants and the survival of patients were recorded. RESULTS: Fifteen recurrent patients were enrolled with 12 glioblastomas and 3 anaplastic gliomas. Among 15 patients, 3 were treated with 3 implants (60 mg of BCNU), 3 with 6 implants (120 mg), 3 with 9 implants (180 mg) and 6 with 12 implants (240 mg). No dose-limiting toxicity was observed in the cohort of patients. Subgaleal effusion was the most common adverse event, presenting in 7 patients (46.7%). The median overall survival (OS) was 322 days (95% CI, 173 - 471 days). The 6-month, 1-year and 2-year survival rates were 66.7%, 40% and 13.3%, respectively. CONCLUSIONS: The high-dose BCNU-loaded PLGA implants were safe for Chinese patients with recurrent malignant gliomas and further investigation for efficacy is warranted.
Abstract 3669: Autocrine interleukin/STAT3 signaling in breast implant-associated T cell anaplastic large cell lymphoma cell lines suggests a mechanism for tumor progression and effective therapy
Authors: Connor H. Church, Melissa G. Lechner, Carolina Megiel, Rikki S. Bass, Sarah M. Russell, Alan L. Epstein
Journal: Cancer Research (2012)

Abstract Recently, over 80 cases of anaplastic large-cell kinase (ALK)-negative, T-cell, anaplastic, non-Hodgkin lymphomas (T-ALCL) have been identified worldwide in patients with textured saline and silicone breast implants. These breast implant-associated T-ALCL cases are striking for their homogeneous clinical presentation and pathology that is distinct from established classes of ALCL. In order to understand the nature of this newly emerged clinical entity, we have established three new cell lines, designated T cell Breast Lymphoma (TLBR) -1, -2, and -3, from patient primary tumor biopsy specimens. Characterization of these pre-clinical models confirmed fidelity to the original tumor biopsy specimens and highlighted unique features that may aid the development of effective treatments for these cancers. Gene expression analysis demonstrated significant up-regulation of survivin and down-regulation of pro-apoptotic genes (BID, BAK, BBC3) by all TLBR cell lines relative to healthy donor T cells. This preliminary finding prompted examination of upstream regulators of cell survival in T cells, namely the interleukin signaling associated with the JAK/STAT pathway. TLBR cell lines were found to secrete high levels of IL-6 and IL-10, and were strongly positive for the cognate receptors. The TLBR cell lines also showed elevated levels of STAT3 and pSTAT3 by immunoblotting techniques, along with a simultaneous reduction in expression of the pSTAT3 phosphatase, SHP-1. These results implicate an unregulated autocrine STAT3 pathway present in the TLBR cell lines that strongly contributes to their tumorigenesis. Assays of various inhibitors of this pathway support this hypothesis since targeting of STAT3 with the tyrosine kinase inhibitor, Sunitinib, led to dramatic in vitro cell death in all TLBR cell lines. More specific inhibition of STAT3 with S3I-201 had comparable results with Sunitinib. Furthermore, IL-6 neutralization by a monoclonal antibody or SHP-1 restoration by 5-azacytidine treatment also demonstrated moderate efficacy in inhibiting TLBR cell line growth in vitro. These discoveries strongly suggest the use of these reagents in the clinical treatment of Breast Implant Associated T-ALCL. The TLBR cell lines closely resemble the primary breast implant-associated lymphomas from which they were derived, and as such provide valuable preclinical models to study the unique biology and provide clinicians with improved knowledge for treatment and diagnosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3669. doi:1538-7445.AM2012-3669
Book ReviewBlood Cells: A practical guide
Authors: Dennis W. Ross
Journal: New England Journal of Medicine (1990)

Here is a procedural manual and morphologic atlas of laboratory hematology. The author presents methods in stepwise fashion: phlebotomy, preparing a blood smear, and performing a blood count with automated instruments. Next is the morphology of normal peripheral-blood cells. Qualitative abnormalities on the smear are correlated with the quantitative results of the complete blood count. This portion of the book includes color pictures and atlas-like descriptions. The accompanying two-color tables are quite useful. There is a chapter on normal ranges for the complete blood count, followed by one on supplementary cytochemical stains. The author then presents the abnormal morphologic features …
Erythropoietin Treatment of Anemia Associated with Multiple Myeloma
Authors: Heinz Ludwig, Elke Fritz, Harald Kotzmann, Paul Höcker, Heinz Gisslinger, Ursula Barnas
Journal: New England Journal of Medicine (1990)

Anemia is a common complication of multiple myeloma. It resolves early in the disease if chemotherapy induces a complete remission, but persists if the disease progresses, causing disabling symptoms and often requiring blood transfusions. We treated 13 patients with myeloma-associated anemia by administering recombinant human erythropoietin three times a week for six months. Eleven patients (85 percent) had steady increases in hemoglobin levels and eventual correction of the anemia. Their symptoms of anemia subsided, and they reported a heightened sense of well-being. No patient had any adverse side effects, particularly episodes of hypertension. Monitoring of the serum M component showed a predominantly stable tumor load without apparent interaction between the underlying disease and the response to erythropoietin therapy. The number of erythroid burst-forming units in the bone marrow and peripheral blood and the level of erythropoiesis in bone marrow smears increased significantly during therapy. Pretreatment serum levels of erythropoietin were higher in the patients who did not respond and in those who required more than two months of treatment before they responded. Serum iron, ferritin, and transferrin concentrations reflected responses to treatment. We conclude that recombinant human erythropoietin is a promising therapeutic tool for treating myeloma-associated anemia.
Abstract 1464: <i>In vitro</i> culturing of CTCs/DTCs in personalized cancer management.
Authors: Vladimir Bobek
Journal: Cancer Research (2013)

Abstract Subsequent detection, quantification and molecular characterization of CTCs has an enormous potential in numerous of oncology areas. But detection and isolation of CTCs is technically quite challenging. The whole dissemination process encompasses also individual tumor cells which are found in relatively big quantities in peritoneal washings (PW) and pleural effusions (PE), so called disseminated tumor cells (DTCs). Thanks in vitro cultures of separated CTCs/DTCs we were able to introduce additional chemosensitivity testing for the purpose of individualized cancer treatment. We present an isolation and cultivation of CTC/DTC of non-small cell lung cancer and gastrointestinal cancers (esophageal cancer, colorectal cancer, gastric cancer, pancreatic cancer) describing cultivation methodology on patients case studies. The cancer cells were separated from body fluids (PW, PE, blood) using the differences in size of cancer cells if compared to other nucleated cells detected in body cavities. After reaching the confluence the chemosensitivity of cell cultures has been tested by xCELLigence system (RTCA, Roche) for different concentrations of single cis-platinum, gemcitabine and fluorouracyl (incubation time 24-72 hours) or their combinations. The dynamic real-time cell growth monitoring enables parallel or sequential combinations of administered drugs with a direct outcome for patients care. Conclusions: We assume that developing cultivation strategies for CTCs/DTCs could bring us closer to the definition of the CTC/DTC-function within the dissemination process with a perspective to use this knowledge in personalized cancer treatment. Citation Format: Vladimir Bobek. In vitro culturing of CTCs/DTCs in personalized cancer management. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1464. doi:10.1158/1538-7445.AM2013-1464
Epigenetics Differences between Estrogen Receptor (ERS1) and Her2/Neu Status in Breast Cancer Patients.
Authors: J. Martínez-Galán, B. Torres-Torres, I. Ales, G. Durán, V. Gutierrez, R. Del Moral, M. Cobo, M. Nuñez, M. Benavides, M. Ruiz De Almodóvar
Journal: Cancer Research (2009)

Abstract Background: The CpG island methylator phenotype is associated with distinct clinicophatological characteristics as Estrogen Receptor (ESR1) positive and amplification of HER2 in breast cancer.Objetive: To evaluate epigenetics differences in tumor-related genes to ERS1 and HER2/neu status in primary breast cancer.Material and Methods: We quantified methylation levels of promoter of 5 genes (ERS1, RAR- β, 14-3-3 sigma, APC, E-Cadherin) which are to confer growth adventage to cells, in 107 women with breast cancer and 108 control subjects. Real Time QMS-PCR SYBR green (methylation-specific PCR) was used to analyze the hypermethylation. Tumours were classified as phenotype basal, luminal A, Luminal B and phenotype HER2+.Results: Ours analyses revealed low or absent methylation ESR1and 14-3-3σ in healthy controls and significant differences between breast cancer patients (pts) and healthy controls in relative serum levels of methylated gene promoters ESR1 (p=0.0112) and 14-3-3s (p=0.0047). Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p=0.0179). Of the available cases, 60 pts (56%) were Luminal A, 10 pts (9.3%) Luminal B, 13 pts (12%) Basal like and 9 pts (8.4%) HER2+. We observed that methylated ERS1 was preferably associated with phenotype Basal Like and worse interval progression free and survival global though p&amp;gt;0.05 and the amplification HER2+ was correlation with significant more frequent methylation gene (p&amp;lt;0.05). Thet hypermethylation of normal ERS1 and 14-3-3σ combined differentiated between breast cancer patients and healthy controls (p=0.0001) with a sensitivity of 81% (95% CI: 72–88%) and specificity of 88% (95% CI: 78–94%).Conclusions: This study identifies the presence of variations in global levels of methylation promoters genes in healthy controls and breast cancer with different phenotype classes and shows that these differences have clinical significance. These showed that frequent methylation had a strong association with molecular phenotype of breast cancer and perhaps in the future can explain therapy resistance related to RE and HER2/neu status in breast cancer patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1151.
FRI0433 Mri in Neuropsychiatric Lupus: Correlations with the 1999 ACR CASE Definitions:
Authors: M. Her, N. Park, S.-K. Kim, D. Kim, S.W. Lee, W.T. Chung
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Neurological manifestations in systemic lupus erythematosus (SLE) are diverse. Because of its varied manifestations and low prevalence, the ACR has developed nomenclature and case definitions for neuropsychiatric SLE (NPSLE) to facilitate clinical research. Brain MRI has been used for the evaluation of neurologic symptoms. <h3>Objectives</h3> The purpose of this study was to identify characteristic brain MRI findings in NPSLE and to investigate the association between brain MRI findings and NPSLE manifestations. <h3>Methods</h3> In total, 145 brain MRIs in 126 patients with NPSLE from 2002 to 2013 from three tertiary university hospitals were retrospectively reviewed. The images were evaluated for the presence of white matter hyperintensity (WMH), gray matter hyperintensity (GMH), parenchymal defects, atrophy, enhancement, and the abnormalities in diffusion-weighted image (DWI). The number, size and location of WMH,GMH and parenchymal defects were evaluated. The NPSLE manifestations of each patient were classified according to the 1999 ACR case definitions for NPSLE syndromes. The associations between MRI findings and manifestations of NPSLE were examined. <h3>Results</h3> In total, 103 MRIs (71.0%) exhibited abnormalities among the 145 MRIs reviewed. There were 172 NP events that encompassed 16 of 19 NP syndromes. The most common MRI abnormalities were WMHs. One or more WMHs were found in 84 MRIs (57.9%) among the total 145 MRIs. GMHs were observed in 42 MRIs (29.0%). GMHs tended to involve much larger areas than WMHs. Patients with cerebrovascular disease or seizures were more likely to have GMHs than patients with other NP manifestations. 33 MRIs among 42 MRIs which had GMHs also exhibited WMHs. Parenchymal defects were found in 35 MRIs (24.1%). Atrophy was detected in 26 MRIs (17.9%). Brain MRIs were enhanced in 21 of the 126 cases that had undergone enhancement. Patients who had seizures were more likely to demonstrate MRI enhancement than patients with other NP manifestations. DWIs were obtained in 102 MRIs and abnormal DWIs were obtained in 18 MRIs cases. Patients with cerebrovascular disease were more likely to have GMH, parenchymal defects and abnormal DWI than patients with other NP manifestations <h3>Conclusions</h3> Diverse brain MRI abnormalities were observed in the brain MRI of patients with NPSLE. In addition to WMHs, which were previously known as SLE findings, we also noted the presence of GMHs, parenchymal defects and abnormal DWI in a substantial portion of SLE patients, particularly in those with cerebrovascular disease or seizure. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2216