tbuckley/cabot-search huggingface dataset:
Second primary malignancies in hepatocellular carcinoma: A population-based study.
Authors: Binay Kumar Shah, Pujan Kandel, Amit Khanal
Journal: Journal of Clinical Oncology (2015)

9563 Background: A second primary malignancy is a serious long term complication in cancer survivors. The aim of this study was to evaluate the risk of second primary malignancies in patients with hepatocellular carcinoma. Methods: We selected all adult patients ( ≥ 18 years) diagnosed with hepatocellular carcinoma (HCC) from National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) 13 database. We calculated risk of second primary malignancies in the hepatocellular cancer patients using multiple primary standardized incidence ratio (MP-SIR) session of SEER* stat software. Second primary malignancy (SPM) was defined as a metachronous malignancy diagnosed six months or more after an index HCC. Results: A total of 15,296 patients with a diagnosis of primary hepatocellular carcinoma were reported in the SEER* 13 registry during January 1992 to December 2011. A total of 446(2.83%) developed 466 SPMs with an observed/expected (O/E) ratio of 1.07 (95% confidence interval = 0.97-1.17, p < 0.164) and absolute risk of 7.17 per 10,000 populations persons. The median age at diagnosis of HCC was 66.16 years (range: 42.33 - 95.5 years), and median follow up duration of patients was 28 months (range: 6 months – 18.5 years). Significant excess risk was observed for oral and pharyngeal cancers (N = 29, O/E = 1.73, confidence interval = 1.73-3.7, P < 0.01), stomach cancer (N = 20, O/E = 1.78, confidence interval = 1.09-2.75, P < 0.02), hepatobiliary cancer (N = 43, O/E = 2.71, confidence interval = 1.96-3.66, P < 0.002), lung and bronchial cancer (N = 82,O/E = 1.33,confidence interval = 1.05-1.65,P < 0.01),and hematological malignancies (N = 54,O/E = 1.52,confidence interval = 1.14-1.98, P < 0.005). Risk of head and neck cancer, thyroid, Kaposi sarcoma and hematologic malignancies was increased within the first two years of after diagnosis of HCC. Risk of lung and hepatobiliary cancers was increased after two years of latency. Conclusions: There is significant increased risk of second primary malignancies in adult patients with HCC compared to general population. Risk of specific SPM depends on latency.
SAT-352-A combination of the ACC inhibitor GS-0976 and the nonsteroidal FXR agonist GS-9674 improves hepatic steatosis, biochemistry, and stiffness in patients with non-alcoholic steatohepatitis
Authors: Eric Lawitz, Edward Gane, Peter Ruane, Robert Herring, Ziad H. Younes, Paul Kwo, Jie Zhang, Catherine Jia, Jay Chuang, Bryan Mccolgan, Chuhan Chung, Mani Subramanian, Robert Myers, Michael Middleton, Kelvin Li, Marc Hellerstein, Mazen Noureddin, Stephen Harrison, Rohit Loomba
Journal: Journal of Hepatology (2019)
Implications of English-speaking status for end-of-life care in advanced cancer.
Authors: Elizabeth Levin, Michael Ries, Jeffrey B Rubins, Andres Wiernik
Journal: Journal of Clinical Oncology (2015)

e20511 Background: Advance health care directives (AHCD) are recommended by ASCO as a strategy to improve compliance with patient wishes at the end-of-life, and thereby ensure appropriate use of health care resources. Health disparities among minority and underserved cancer patients are well recognized in the oncology community. This study aims to determine variations in obtaining an AHCD and their implications in end-of-life care at Minnesota’s largest safety-net hospital. Methods: Retrospective analysis conducted at Hennepin County Medical Center in Minneapolis, MN with review of the cancer registry data from 2008 to 2013. Data were collected for deceased patients with stage III-IV cancer from the time of diagnosis through death. Demographics, AHCD, hospital deaths, enrollment in hospice, and individual patient data were analyzed. Results: From 2008 to 2013, there were 273 patients diagnosed with stage III-IV cancer with follow-up through death. In our health care system, 45% of patients with advanced cancer died in the hospital and 21% died in the intensive care unit (ICU). We identified that 57% of non-English speaking patients died in the hospital and 27% died in the ICU. Enrollment into hospice care occurred in 49% of our patients, but 60% established hospice care in the last 30 days of life. Completing an AHCD could potentially influence ICU deaths and increase hospice enrollment as 35% of patients who died in the ICU obtained an AHCD and 49% did not (p = 0.21), and 60% of patients that signed an AHCD enrolled in hospice compared to 46% who did not (p = 0.08). Only 21% of patients completed an AHCD during their care, and none of the Asian or Hispanic patients completed an AHCD before dying from cancer. After performing a logistic regression analysis adjusting for both race and language, we found that English speakers were almost five times more likely than non-English speakers to have an AHCD (OR = 4.66, 95% CI = (1.06, 20.46), p = 0.04). Conclusions: Even among patients with non-curable cancer at diagnosis, a large number of patients die in the hospital and in the ICU at our safety-net hospital. Strategies to discuss and educate cancer patients on end-of life care are urgently needed, particularly with non-English speaking patients.
The impact of a <i>Bim </i>deletion polymorphism on the survival of patients with completely resected non-small cell lung cancer.
Authors: Jun Atsumi, Kimihiro Shimizu, Kyoichi Kaira, Toshiteru Nagashima, Yoichi Ohtaki, Kai Obayashi, Seiichi Kakegawa, Osamu Kawashima, Mitsuhiro Kamiyoshihara, Masayuki Sugano, Izumi Takeyoshi
Journal: Journal of Clinical Oncology (2015)

7531 Background: A deletion polymorphism of the Bim gene is observed in the Asian population; this polymorphism has been reported to be a prognostic factor for non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy. We investigated the impact of the Bim deletion polymorphism on the survival of patients with completely resected NSCLC. Methods: Distribution of the Bim polymorphism was detected using polymerase chain reaction analysis from peripheral neutrophils in samples from 412 NSCLC patients who underwent complete resection. We measured overall survival (OS) and disease free survival (DFS) in all eligible patients, and post-recurrence survival (PRS) in 98 patients who developed recurrences and received anti-cancer therapy. Results: The Bim deletion polymorphism was detected in 63 (14.0%) patients. OS and DFS rates were significantly lower for patients with the Bim deletion polymorphism than those with wild type (OS, P < .001; DFS, P = .006). On multivariable analysis, Bim deletion polymorphism was identified as an independent prognostic factor for OS (hazard ratio [HR] = 1.99; 95% confidential interval [CI], 1.18 to 3.38; P = .010), but not for DFS (HR = 1.19; 95% CI, 0.78 to 1.98; P = .367). Among the 98 patients who developed recurrences and were treated with anticancer therapy, patients with the Bim deletion polymorphism had a significantly worse PRS than those with wild type (median 11.4 months vs 26.9 months, respectively, P < .001). This trend was consistent with subgroup analysis stratified by EGFR mutation status (P = .001 for EGFR mutant group; P = .002 for EGFR wild type group) or histology (P = .012 for adenocarcinomas; P = .013 for non-adenocarcinomas). A multivariate analysis suggested that the Bim deletion polymorphism is an independent predictor of PRS (HR = 2.99; 95% CI, 1.58 to 5.50; P = .001). Conclusions: The Bim deletion polymorphism is a novel indicator of shorter PRS among patients with recurrent NSCLC treated with anticancer therapy in the Asian population.
FRI-244-Platelet-derived growth factor alpha might mediate hepatic fibrosis by enhancing insulin resistance in patients with hepatitis C
Authors: Anna Mrzljak, Davorka Dusek, Kristina Blaslov, Snjezana Zidovec Lepej, Ivana Grgić, Lana Gorenec, Iva Košuta, Adriana Vince
Journal: Journal of Hepatology (2019)
Annals Graphic Medicine - Progress Notes: House of Cards
Authors: Michael Natter
Journal: Annals of Internal Medicine (2019)

Web Exclusives16 April 2019Annals Graphic Medicine - Progress Notes: House of CardsFREEMichael Natter, MDMichael Natter, MDNYU School of Medicine, New York, New York (M.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0006 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: NYU School of Medicine, New York, New York (M.N.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0002.Author/Illustrator Information: Michael Natter, MD, is a current internal medicine resident at NYU School of Medicine and a graduate of Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia. His artwork is inspired by his medical training, patient encounters, and the human condition. A type 1 diabetic, Dr. Natter views himself as a patient as well as a doctor and plans to pursue a fellowship in endocrinology to help others who also share his disease. You can find more of his illustrations, stories, and comics on Instagram (www.instagram.com/mike.natter) and Twitter (@mike_natter).About Progress Notes: Progress Notes explores the everyday emotional, clinical, humorous, and ethical challenges of the medical residency training process. As implied by the title of the series, these pieces act as a visual bildungsroman, graphically dissecting the subtext of what it means to be a young doctor in today's medical world. Progress Notes appears monthly in Annals Graphic Medicine at Annals.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 April 2019Volume 170, Issue 8Page: W88-W89KeywordsConflicts of interestDisclosureEmotionsEndocrinologyFellowshipsGraduate medical educationResidency ePublished: 16 April 2019 Issue Published: 16 April 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Vaping and Pregnancy
Authors: Bridget Kuehn
Journal: JAMA (2019)

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Feasibility and utility of transbronchial cryobiopsy in primary lung cancer: Prospective, single arm study
Authors: K. Kirita, H. Udagawa, S. Matsumoto, K. Yoh, S. Niho, K. Goto
Journal: Annals of Oncology (2019)

Background: Transbronchial forceps biopsy (FB) is the standard diagnostic tool for primary lung cancer. Recently, we need much amount of tissues for pathological diagnosis, mutational analysis and immunohistochemistry (IHC). The aim of this study was to prospectively evaluate safety, utility for diagnosis of primary lung cancer and biomarker analysis using cryoprobe, that was new transbronchial biopsy tool. Methods: A total of 128 patients with suspected of primary lung cancer were enrolled in this single arm trial and 121 patients were performed both transbronchial normal FB and transbronchial cryobiopsy (TBCB). We evaluated safety especially in bleeding and pneumothorax, diagnostic yield of malignancies, morphological diagnosis, size, tumor concentration of tissue samples and success rate of biomarker analysis. Results: Total diagnostic yield of TBCB was 92% (111/121), in details, 97% (62/64) in central bronchial lesions and 86% (49/57) in peropheral lung lesions. TBCB samples were more useful for morphological classification (86% vs. 79%), and larger size (median size was 15mm2vs. 2mm2, p < 0.001) than FB samples. The ratio of containing malignant cells in each FFPE samples were higher in TBCB (84% (148/177)) than in FB (73% (285/391)). TBCB was more useful for mutational analysis and PD-L1 IHC. Severe bleeding (need to sprinkle hemostatic) was observed each 1 case and grade 3 lung infection (need hospitalization and IV antibiotics) occurred in 4 patients (3%). There was no case of pneumothorax. Conclusions: TBCB is safe technique and useful for diagnosis of primary lung cancer. Furthermore, we could obtain more quantity and better quality of sample for diagnosis and biomarker analysis in comparison with conventional FB. Legal entity responsible for the study: National Cancer Center Hospital. Funding: Japan Agency for Medical Research and development (15ck106111h0002). Disclosure: All authors have declared no conflicts of interest.
Abstract 15178: A Neprilysin Inhibitor, Sacubitril, Fails to Improve Ventricular Contractility and Worsens Vascular Function in Heart Failure
Authors: David J Polhemus, Rishi K Trivedi, Zhen Li, Hiroshi Koiwaya, Craig Zibilich, David J Lefer
Journal: Circulation (2017)

Introduction: Neprilysin is an endopeptidase that degrades various peptides that regulate cardiovascular function such as the natriuretic peptides (NPs), bradykinin, and angiotensin II (Ang II). Given the cardioprotective and vasculoprotective effects of the NPs, neprilysin inhibitors are under investigation for the treatment of heart failure (HF). We examined the effects of a neprilysin inhibitor, Sacubitril, on cardiac and vascular function in a rat model of HF. Methods: Male Wistar-Kyoto rats were subjected to 45 min of transient LAD coronary artery ligation followed by reperfusion for 12w. At 4w following reperfusion, rats were treated with sacubitril (37 mg/kg/day) or Vehicle Control in the drinking water. At 12w following reperfusion, thoracic aortas were harvested and vascular reactivity to the endothelium-dependent vasodilator, acetylcholine (ACh), and the endothelium- independent vasodilator, sodium nitroprusside (SNP) was evaluated. LV function (i.e. ejection fraction) and structure was assessed...
Inhibition of AKT3 to increase migration and metastasis by upregulation of S100A4 protein expression.
Authors: Florian Ewald, Astrid Grottke, Tobias Lange, Udo Schumacher, Bjoern Nashan, Manfred Juecker
Journal: Journal of Clinical Oncology (2015)

11023 Background: The treatment of patients with distant metastases represents one of the biggest challenges in modern oncology, and the occurrence of metastases often determines the prognosis of the disease. Therefore, understanding the mechanisms facilitating the development of metastasis is of paramount importance. It was previously shown that activation of the PI3K/AKT pathway is a requirement for the ability of tumour cells to disseminate and form metastases. However, single AKT isoforms (AKT1, AKT2 and AKT3) were shown to have different, and even opposing functions regarding the regulation of cancer cell migration in vitro, giving rise to the hypothesis that inhibition of distinct AKT isoforms might have undesirable effects on cancer progression. The aim of this project therefore is to investigate the functions of the specific AKT isoforms regarding migration and metastasis of cancer cells. Methods: Three cell lines were used to generate single and double AKT isoform knockdown cells. Migration and invasion of these cells was analysed in vitro using live imaging migration, chemotaxis, and invasion assays. Metastatic potential of AKT isoform knockdown MDA-MB-231 cells was evaluated in a subcutaneous xenograft mouse model in vivo. Results: Knockdown of AKT3, but not AKT1 or AKT2, results in increased migration and scattering in vitro, and this effect was even more pronounced in AKT2/AKT3, and AKT1/AKT3 double knockdown cells. Furthermore, we were able to demonstrate that knockdown of AKT2/AKT3 and AKT1/AKT3 results in an increased number of lung metastasis, as detected by Alu PCR and upon histological examination. We found that AKT3 specifically regulates the expression of the metastasis promoting protein S100A4 via regulation of NFAT5 in MDA-MB-231 cells, and knockdown of S100A4 or NFAT5 were able to reverse the AKT3 induced increase in migration. Conclusions: Our study provides novel insight into the specific contribution of each AKT isoform to the regulation of migration and metastasis, and our results indicate that inhibition of AKT3 might cause adverse effects on cancer dissemination and progression. Therefore, our results provide a rationale for the development of AKT isoform specific inhibitors.
PS-011-New synthetic conjugates of ursodeoxycholic acid inhibit hepatorenal cystogenesis in experimental models of polycystic liver disease
Authors: Francisco Javier Caballero, Ivan Rivilla, Elisa Herraez, Alvaro Santos-Laso, Laura Izquierdo-Sánchez, Pui Yuen Lee-Law, Pedro Miguel Rodrigues, Sergio Gradilone, Manel Esteller, Luis Bujanda, Jose Marin, Fernando Cossio, Jesús María Banales
Journal: Journal of Hepatology (2019)
Abstract 19091: Association Between Hypertension and Thoracic Aorta Calcification of a Large Asian Population
Authors: Chun-Ho Yun, Chung-Lieh Hung, Wei-Ming Huang
Journal: Circulation (2017)

Introduction: Hypertension promotes atherosclerosis and is one of the most important cardiovascular risk factors. However, the association between hypertension and thoracic aortic calcification (TAC) in the general Asian population remains unknown. Hypothesis: The aim of this study was to quantify TAC using multi-detector computed tomography (MDCT) and examine whether blood pressure levels are associated with TAC in the normotension, prehypertension and hypertension populations in Taiwan. Methods: We studied a nonselective, consecutive population of 2,986 Asians including 1,093 normotension, 1081 prehypertension, and 812 overtly hypertension subjects who underwent an annual health survey. Measures of TAC included total Agatston score, total plaque volume and mean density (HU) of plaques using a non-contrast 16-slice multi-detector computed tomography with off-line processing. Results: Patients with hypertension and prehypertension had greater Agatston score, total plaque volume and mean density (HU) of pl...
Circulating tumor cells (CTCs) in systemic prostate cancer.
Authors: Dmitry Aleksandrovich Shvyrev, Oleg Ivanovich Kit, Inna Arnoldovna Novikova, Alexey N. Shevchenko, Andrey Vladimirovich Bakhtin, Olesya N. Selyutina, Sergey G. Seleznev, Aleksandr V. Faenson, Sergey N Dimitriadi, Mikhail V. Tarakanov, Irina A. Khomutenko
Journal: Journal of Clinical Oncology (2015)

e22019 Background: The purpose of the study was to evaluate quantitatively CTCs in peripheral blood of patients with stage III-IV prostate cancer. Methods: 30 patients with systemic prostate cancer (adenocarcinoma G2-G3) with liver and bone metastases aged 58-83 years (mean age 71.6±3.9) were recruited. CellSearch Veridex System (Janssen) was used for CTCs detection. CellTracks Analyzer II was used for scanning the material. CTCs were registered taking into account morphologic characteristics and expression of epithelial cell adhesion markers EpCAM, CD45 and cytokeratins 8, 18, 19. Results: CTCs in peripheral blood were detected in 70% of the cases: 1-3 cells – 42.9%, 3-10 cells – 28.6%, over 10 cells – 28.6%. Quantity of tumor cells in the studied samples ranged from 1 to 190 cells in 7.5 ml of blood sample. CTCs were detected in 60% of patients with G2 adenocarcinoma and in 80% with G3 adenocarcinoma. CTCs were found in all patients with liver metastases and with liver and bone metastases, with their maximum in a patient with liver metastases. CTCs were detected in 57.1% in patients with bone metastases. Absence or lower content of CTCs in comparison with reference values could be caused by the effectiveness of hormonal and radiation therapy. Conclusions: The results prove CTCs to be a prognostic factor for the clinical course of the disease and effectiveness of hormonal and radiation therapy, as well as a prognostic tumor marker of a new generation affecting the choice of treatment and controlling its effectiveness.
SAT-417-Serum levels of keratin 19 fragments (CYFRA 21-1) are elevated in advanced liver disease and predict poor survival
Authors: Karim Hamesch, Nurdan Gueldiken, Aly Mahmoud, Norbert Hueser, Daniel Hartmann, Christian Trautwein, Sebastian Mueller, Pierre Rufat, Pierre Nahon, Marianne Ziol, Tony Bruns, Pavel Strnad
Journal: Journal of Hepatology (2019)
Association of intravenous (IV) and intramuscular (IM) pegaspargase (PEG) administration with rate of adverse events (AE) in standard risk (SR) Acute Lymphoblastic Leukemia (ALL) Children’s Oncology Group (COG) trials.
Authors: Kelly W. Maloney, Anne L. Angiolillo, Reuven J. Schore, Meenakshi Devidas, Xiaomin Lu, Cindy Wang, Alison M. Friedmann, Leonard A. Mattano, Mignon L. Loh, Elizabeth A. Raetz, Linda C. Stork, Naomi J. Winick, Stephen Hunger, William L. Carroll
Journal: Journal of Clinical Oncology (2015)

10035 Background: COG AALL0331 administered PEG IM in induction (IND) and Delayed intensification (DI) whereas AALL0932 administers the same dose IV. We compared grade 3/4 toxicities resulting from the single doses of PEG given in the IND and DI phases on the standard arms of AALL0331 and AALL0932 that gave only 2 doses of PEG (excluded arms with additional PEG). Methods: AALL0331 and AALL0932 shared a common 3 drug IND: dexamethasone (DEX) 6 mg/m2/day X 28 days, vincristine (VCR) 1.5 mg/m2/dose on days 1, 8, 15, 22, IT methotrexate (age adjusted dosing) on days 8, 29, and PEG 2500 units/m2/dose IM on day 4, 5, or 6 (AALL0331) or IV on day 4 (AALL0932). DI (Days 1-28) for both protocols consisted of: DEX 10 mg/m2/day (days1-7, 15-22), VCR 1.5 mg/m2/dose and Doxorubicin 25 mg/m2/dose IV (days 1, 8, 15), PEG 2500 units/m2on day 4 (AALL03131 IM; AALL0932 IV). Toxicity was graded using CTCAE v4.0, however, AALL0331 collected data using CTCAE v3.0, which was subsequently mapped to v4.0. Results: During IND, the rates of anaphylaxis/allergic reaction were similar between IM and IV PEG (0.2% vs. 0.3%, p = 0.842). The rate of anaphylaxis/allergic reaction in DI was 0.5% (IM) vs 1.8% (IV) (p = 0.007). The rates of pancreatitis, elevated lipase and amylase, and hyperglycemia were similar between IM and IV PEG in both IND and DI. Conclusions: The rates of AEs with PEG administration (IV or IM) are low but more grade 3/4 anaphylaxis/allergic reactions were reported with IV PEG compared to IM PEG during DI. This may be due to more stringent reporting on 0932 or the challenges of determining infusion reactions vs. allergic reactions when PEG is administered IV. Clinical trial information: NCT00103285. Toxicities (%) Grades AALL0331 AALL0932 p-value Allergic reaction/ Anaphylaxis IND DI 3-4 0.2 0.5 0.3 0.8 0.84 0.0007 Pancreatitis IND DI 3-4 0.5 0.4 0.8 0.3 0.07 0.79 Lipase increased IND DI 4 0.6 0.4 0.4 0.3 0.22 0.39 Serum amylase increased IND DI 4 0.3 0.1 0.2 0.1 0.53 1.00 Hyperglycemia IND DI 4 1.1 0.4 1.3 0.1 0.46 0.02 Glucose intolerance IND DI 4 0.02 0 0 0 1.0 ----