tbuckley/cabot-search huggingface dataset:
Computer-aided detection of early neoplastic lesions in Barrett’s esophagus
Authors: Fons van der Sommen, Svitlana Zinger, Wouter Curvers, Raf Bisschops, Oliver Pech, Bas Weusten, Jacques Bergman, Peter de With, Erik Schoon
Journal: Endoscopy (2016)

<b>Background and study aims:</b> Early neoplasia in Barrett's esophagus is difficult to detect and often overlooked during Barrett's surveillance. An automatic detection system could be beneficial, by assisting endoscopists with detection of early neoplastic lesions. The aim of this study was to assess the feasibility of a computer system to detect early neoplasia in Barrett's esophagus. <b>Patients and methods:</b> Based on 100 images from 44 patients with Barrett's esophagus, a computer algorithm, which employed specific texture, color filters, and machine learning, was developed for the detection of early neoplastic lesions in Barrett's esophagus. The evaluation by one endoscopist, who extensively imaged and endoscopically removed all early neoplastic lesions and was not blinded to the histological outcome, was considered the gold standard. For external validation, four international experts in Barrett's neoplasia, who were blinded to the pathology results, reviewed all images. <b>Results:</b> The system identified early neoplastic lesions on a per-image analysis with a sensitivity and specificity of 0.83. At the patient level, the system achieved a sensitivity and specificity of 0.86 and 0.87, respectively. A trade-off between the two performance metrics could be made by varying the percentage of training samples that showed neoplastic tissue. <b>Conclusion:</b> The automated computer algorithm developed in this study was able to identify early neoplastic lesions with reasonable accuracy, suggesting that automated detection of early neoplasia in Barrett's esophagus is feasible. Further research is required to improve the accuracy of the system and prepare it for real-time operation, before it can be applied in clinical practice.
Abstract 1414: Molecular and functional characterization of ovarian cancer stem cells
Authors: Michela Lupia, Giovanni Bertalot, Nicoletta Colombo, Stefano Confalonieri, Pier Paolo Di Fiore, Ugo Cavallaro
Journal: Cancer Research (2015)

Abstract Epithelial Ovarian Cancer (OC) is one of the leading causes of death for women, and no significant therapeutic progress has been made in the last decades. Recent data suggest that one of the mechanisms accounting for resistant and/or relapsing disease is a subpopulation of cells in human tumors with stem-like characteristics (cancer stem cells, CSCs). CSCs are defined as a small subpopulation of cells within the tumor bulk that possess the capacity, on one hand, to self-renew and, on the other hand, to give rise to all heterogeneous cancer cell lineages that compose the tumor of origin. The CSC hypothesis provides an attractive cellular mechanism to explain the therapeutic refractoriness, dormant behavior, and relapse of the disease. Our study aims at assessing ovarian cancer stem cells (OCSC) as causal players in OC etiology and progression and at defining their molecular and functional profile. Specifically, we are pursuing the following objectives through the accomplishment of these milestones: 1) collection of normal and pathological samples; 2) identification of OCSC based on functional properties; 3) comparison of gene expression profiles between cancer stem cells and their normal counterpart; 4) characterization of novel genes/pathways involved in OCSC function (clonogenicity, tumorigenicity, quiescence, chemoresistance, etc.). This workflow is being applied to a series of fresh surgical samples of OC as well as to normal ovarian surface epithelium (OSE) and fallopian tube epithelium (FTE), namely the tissues of origin of OC. Thus, we obtained a collection of primary cells that recapitulate many traits of the original tissue both in vitro and in vivo. The gene expression profiles of sphere-forming SC has been compared to that of adherent, parental cells, aimed at identifying stemness-associated genes. This screening has been extended to OC, OSE, and FTE, resulting in a set of genes that are differentially expressed in OCSC as compared to their normal counterparts. A subset of such genes has been selected for the subsequent validation, both as OCSC biomarkers that could have clinical applications and as drivers in the biological and pathogenic function of OCSC. Our study might set the stage for innovative therapeutic approaches aimed at the selective elimination of OCSC, thus preventing tumor recurrence and chemoresistance, namely the two main causes of ovarian cancer lethality. Citation Format: Michela Lupia, Giovanni Bertalot, Nicoletta Colombo, Stefano Confalonieri, Pier Paolo Di Fiore, Ugo Cavallaro. Molecular and functional characterization of ovarian cancer stem cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1414. doi:10.1158/1538-7445.AM2015-1414
Stimulation of F-Cell Production in Patients with Sickle-Cell Anemia Treated with Cytarabine or Hydroxyurea
Authors: Robert Veith, Renzo Galanello, Thalia Papayannopoulou, George Stamatoyannopoulos
Journal: New England Journal of Medicine (1985)

To investigate the mechanism of pharmacologic stimulation of fetal hemoglobin in sickle-cell anemia (hemoglobin S disease), we treated two patients with homozygous disease with various doses of cytarabine (also known as Ara-C) or hydroxyurea and evaluated the effects of each treatment on F-reticulocyte production and on hemopoiesis. The treatments stimulated F-cell production in a dose-related fashion. Treatments that increased F-cell production also increased the patient's hematocrit and caused only minor, transient decreases in white cells. The main effect on erythropoiesis consisted of cytoreduction of the mature erythron (as assessed by measurements of reticulocytes) or a decrease in the compartment of erythroid progenitors (colony-forming units-erythroid and burst-forming units—erythroid). The reduction phase was followed by reticulocyte regeneration, during which most of the increase in the absolute numbers of F reticulocytes took place. Lower doses of cytarabine or hydroxyurea resulted in smaller waves of reticulocyte regeneration and lesser effects on F-reticulocyte production. These results suggest that the main cause of stimulation of fetal hemoglobin in patients with sickle-cell anemia treated with cell cycle—specific compounds is the erythroid regeneration triggered by the drug treatment. (N Engl J Med 1985; 313: 1571–5.)
Case 43-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, T.L. Munsat, J.A. Golden
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 70-year-old man was admitted to the hospital because of a neuromuscular disorder complicated by agitated depression.There was a seven-year history of diabetes mellitus that was managed with insulin during the six years before entry. The patient was well otherwise until 11 months earlier, when he began to have weakness in the right upper extremity that soon spread to the left upper extremity. Two months later he was unable to take his customary one-hour daily walk without stopping to rest every five minutes, and he experienced easy fatigability of the hands and stiffness of the neck . . .
P42 Factors affecting the duration of acute non invasive ventilation required in patients with acute hypercapnic respiratory failure
Authors: A Bishopp, N Sayeed, A Oakes, B Beauchamp, B Chakraborty, R Mukherjee
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Factors predicting the likelihood of failure of NIV, i.e. requirement of intubation or death, have been well documented with low pH shown to be the most important factor. Factors affecting the duration of NIV required in those patients who receive ward base treatment without the need for intubation have not been established. This study aimed to identify factors which influence the duration of NIV required in acute hypercapnic respiratory failure. <h3>Methods</h3> A retrospective analysis of 123 consecutive episodes of acute hypercapnic respiratory failure requiring NIV between June 2013 and June 2014 was carried out. Correlation between duration of NIV treatment and a number of variables, namely admission creatinine, pH, worst arterial carbon dioxide level (CO<sub>2</sub>) and presence and severity of chronic kidney disease (CKD) was assessed by simple linear regression. <h3>Results</h3> There was a statistically significant regression coefficient between worst observed CO<sub>2</sub> and the duration of NIV (fitted equation: NIV Duration = 4.281 + 14.357 × Worst CO<sub>2</sub>, p = 0.019). The plotted linear relationship showed an increase in duration of NIV treatment of 14.35 h for every 1 kPa increase in CO<sub>2</sub> above 6 kPa. The admission creatinine and severity of CKD did not significantly alter the duration of NIV required. The presence of acute kidney injury was also not significant. The pH value did not significantly alter the duration of NIV treatment. <h3>Conclusion</h3> This survey shows that the level of CO<sub>2</sub> influences the duration of acute NIV required, in that for every 1 kPa rise in CO<sub>2</sub>, the duration of acute NIV treatment rises by 14.35 h. The other studied variables do not correlate with treatment duration.
PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma
Authors: Paul T. Nghiem, Shailender Bhatia, Evan J. Lipson, Ragini R. Kudchadkar, Natalie J. Miller, Lakshmanan Annamalai, Sneha Berry, Elliot K. Chartash, Adil Daud, Steven P. Fling, Philip A. Friedlander, Harriet M. Kluger, Holbrook E. Kohrt, Lisa Lundgren, Kim Margolin, Alan Mitchell, Thomas Olencki, Drew M. Pardoll, Sunil A. Reddy, Erica M. Shantha, William H. Sharfman, Elad Sharon, Lynn R. Shemanski, Michi M. Shinohara, Joel C. Sunshine, Janis M. Taube, John A. Thompson, Steven M. Townson, Jennifer H. Yearley, Suzanne L. Topalian, Martin A. Cheever
Journal: New England Journal of Medicine (2016)

Merkel-cell carcinoma is an aggressive skin cancer that is linked to exposure to ultraviolet light and the Merkel-cell polyomavirus (MCPyV). Advanced Merkel-cell carcinoma often responds to chemotherapy, but responses are transient. Blocking the programmed death 1 (PD-1) immune inhibitory pathway is of interest, because these tumors often express PD-L1, and MCPyV-specific T cells express PD-1.
Open-Heart Surgery in Octogenarians
Authors: L. Henry Edmunds, Larry W. Stephenson, Richard N. Edie, Mark B. Ratcliffe
Journal: New England Journal of Medicine (1988)

One hundred consecutive patients 80 years of age or older consented to and subsequently underwent open-heart operations at our institution between July 1976 and May 1987. Fifty of the patients had aortic valvular disease (28 with coexisting coronary artery disease), and 41 had isolated coronary artery disease. Eight patients had mitral valvular disease, and one had a dissecting aortic aneurysm. Ninety had Class IV disease that was functional, ischemic, or both. The most compelling indications for operation in 85 patients were unstable or postinfarction angina, syncope, acute pulmonary edema, or cardiogenic shock. Twenty-nine patients died soon after operation (within 90 days). New York Heart Association Class IV disease, previous myocardial infarction, cachexia, and emergency operation were preoperative variables associated with early death. Forty-three patients had no complications except for atrial arrhythmias and were discharged from the hospital a mean (±SD) of 11.5±3.7 days after operation. Low cardiac output, acute myocardial infarction, reoperation for bleeding, renal insufficiency, pneumonia, and prolonged endotracheal intubation were the most common serious postoperative complications. Twenty-eight patients who survived postoperative complications were discharged 24.9±19.6 days after operation. Seventeen patients died 2 to 104 months after discharge from the hospital. Actuarial calculation predicts the survival of 59 percent of patients at three years and 54 percent at five years. Of the 54 patients still alive at this writing, 53 have disease within New York Heart Association and Canadian Cardiovascular Society Classes I or II. For selected octogenarians with unmanageable cardiac symptoms, operation may be an effective therapeutic option. (N Engl J Med 1988; 319:131–6.)
Duration of disease control (DDC) or time to failure of strategy (TFS) to evaluate a chemotherapy strategy in advanced colorectal cancer (ACC)
Authors: B. Chibaudel, C. Tournigand, N. Perez-Staub, O. Bourges, F. Maindrault-Goebel, T. André, G. Lledo, C. Louvet, F. Bonnetain, A. de Gramont
Journal: Journal of Clinical Oncology (2009)

4073 Background: Progression-free survival (PFS) is not an optimal endpoint in therapeutic strategies evaluating either stop and go or alternated therapies, or a fixed sequence of two therapies. DDC (Tournigand, JCO 2006) and TFS (Allegra, JCO 2007) composite endpoints have been proposed to evaluate efficacy of these strategies in ACC. This study compared these two alternative endpoints. Methods: DDC is defined as the sum of the PFS of each sequence, except when progressive disease is observed at either reintroduction or second-therapy (DDC=PFS1+PFS2 if treatment 2 achieved stabilization or response). TFS is defined as the total PFS from the initiation of the strategy to disease progression while on all the planned agents, or disease progression during a treatment-free interval and no further therapy received within 1 month, or death (TFS=PFS 1+2). Both DDC and TFS have been calculated in three trials: OPTIMOX1 (oxaliplatin stop and go vs continuous administration, updated database, Tournigand, JCO 2006), OPTIMOX2 (oxaliplatin stop and go vs complete stop and go, updated database, Maindrault-Goebel, ASCO 2007) and C97–3 (FOLFIRI1- FOLFOX6 or reverse sequence, Tournigand 2004). Results: The median potential follow-up time was 39.8 months. There was a moderately shorter DDC than TFS in the two stop and go studies, but a much shorter DDC than TFS in the sequential therapy study. There was a significant correlation between DDC and OS (r=0.96, p=.002) but not between TFS and OS (r=0.71, p=.11) Conclusions: Two bias impacted TFS 1) the results of resuming the planned therapeutic strategy for progression after a chemotherapy-free interval of more than one month was not considered, 2) patients who were not progressive at the end of planned strategy could not be censored at that time. The shorter duration of DDC over TFS may have an advantage in terms of sample size for evaluation of therapeutic strategies. In case of drug registration, DDC does not increase in case of inactive second sequence. [Table: see text] No significant financial relationships to disclose.
The significance of KRAS mutations in advanced ovarian cancers treated by multitargeted therapy in Thailand.
Authors: T. Prempree
Journal: Journal of Clinical Oncology (2010)

e15554 Background: The treatment of ovarian cancer has been surgery followed by various forms of chemotherapeutic agents. Recent advances in targeted therapy along with relatively poor response of ovarian cancer to the treatment have been stimulating our interest into studying multitargeted therapy. Objectives: 1) To determine the KRAS mutation in ovarian cancer patients recieving targeted therapy. 2) To determine the KRAS mutation as a predictor to the response. 3) To modulate the treatment in the presence of KRAS mutation. Methods: 12 cases of advanced and recurred (stage IV) ovarian cancers who had exhausted all chemotherapeutic treatments were included in the study. To select the targets for the treatment, we examined the VEGF, EGFR, cKIT and HER2 gene products by IHC (immunohistochemical) technique. All 12 cases recieved 2 targeted therapy. 7 cases recieved bevacizumab + sunitinib. 4 cases recieved bevacizumab + EGFR TKI. 1 case recieved bevacizumab + trastuzumab. Evaluation of the treatment was done by using symptoms improvement, tumor markers, and CT image. Results: 3-months response = 10/12 (83.3%). KRAS mutations = 5/12 (41.6%). 6-12 months response = 3/12 (25%). Conclusions: We had an excellent first 3-months response, perhaps due to good target treatment and no resistance. The built-in tumor resistance occurred during the course of chemotherapeutic treatment has been documented in 5 of 12 cases rebiopsy after 3 months passed. These 5 cases original tumor tissues did not have KRAS mutation before. It appeared that the activating KRAS mutation would interfere with our overall long term result. In all cases of KRAS mutation, we have been trying to block the PI-3K pathway such as using mTOR inhibitor with some success. For future plan of the multitargeted therapy, we would encourage rebiopsy of the tumor and study various target including KRAS mutation study prior to initiating the treatment. No significant financial relationships to disclose.
Adjuvant postoperative chemoradiotherapy in gastric carcinoma
Authors: M. P. Escudero, V. Alonso, J. Valencia, R. Lastra, R. Grandez, S. Polo, A. Ruiz de Lobera, E. Polo, A. Anton, A. Tres
Journal: Journal of Clinical Oncology (2004)

4168 Background: To evaluate the impact of postoperative external radiation therapy combined with 5-Fluorouracil (5FU)-based chemotherapy on the disease-free and overall survival of patients with resected gastric adenocarcinoma. Methods: Patients with pathological T3/T4 or N+ gastric adenocarcinoma were treated with postgastrectomy chemoradiotherapy. External radiotherapy was administered to the tumor bed and regional nodes, and 2 cm beyond the proximal and distal margins of resection (45 Gy/25 fractions). Radiation was delivered with 18-MV photons, and CT-images were used by defining the PTV. Chemotherapy: Group A: 5-FU 425 mg/m2/d + LV 20 mg/m2 on days 1–5 every four weeks for two cycles before and after radiation therapy. During radiation therapy with 5-FU protracted continuous infusion (225 mg/m2/d) was administered. Group B: Mitomicin C 20 mg/m2 on day 1 (single dose) followed by Tegafur 500 mg/m2/d for six months, even during radiation therapy Results: 40 patients have been included (20 group A, 20 group B). 26 male/14 female. Median age 65 years (range 34–77). Pathologic stage: II 12p, IIIA 14p, IIIB 7p, IV-M0 7p. R0 28p/R1 12p. Median nodes analyzed 14 (range 3–41). With a median follow-up of 20 months, 21 patients are still alive, 17 free of disease. Relapse: local and regional relapse (in-field recurrence) 6 patients, distant metastases (out-field recurrence) 12 patients and both 5 patients. The median progression-free survival was 20.1 months and the median overall survival was 27.9 months. We did not find any difference in relapse or survival between the two groups. Conclusions: This scheme is feasible and well tolerated. The locoregional relapse rate was low probably due to the radiation therapy addition. However the distant metastases rate and the median overall survival seem to be hardly modified by the treatment. We need to find a better scheme of chemotherapy for further studies in order to improve these results. No significant financial relationships to disclose.
Case 47-1966
Authors: Alfred Kranes, Karoly Balogh
Journal: New England Journal of Medicine (1966)

Presentation of Case First admission. A forty-year-old man entered the hospital because of pain in the neck.Twenty-four years previously progressive loss of vision in the left eye occurred. Examination in the clinic disclosed a mature cataract in the left eye, with absence of light perception; in the right eye markedly dilated arteries and veins connecting with a reddish, bulging area were observed. A diagnosis of von Hippel's disease was made. Four years later he returned for evaluation because of loss of vision in the right eye; the neurologic examination was negative. X-irradiation was directed to the right eye, without . . .
Pancytopenia in a Patient With Hypothyroidism
Authors: Brandon McMahon, Suneel Kamath
Journal: JAMA (2016)

A 25-year-old woman with hypothyroidism presented with recent fatigue and weight loss. A peripheral blood smear and bone marrow biopsy showed megaloblastic changes; laboratory analysis showed pancytopenia and elevated levels of lactate dehydrogenase and vitamin B12. What would you do next?
Case 6-2007
Authors: Donald S. Kaufman, Mansi A. Saksena, Robert H. Young, Shahin Tabatabaei
Journal: New England Journal of Medicine (2007)

A 28-year-old man was referred to this hospital for consultation on the management of an enlarging testicular mass. Ten days before the consultation, the right testicle became tender and began to enlarge rapidly. Treatment with antibiotics resulted in decreased tenderness, but the mass persisted. On examination, a 4-cm mass was palpable within the testis. Ultrasound examination disclosed a complex intratesticular mass.
Cardiogenic Shock after Acute Myocardial Infarction
Authors: Robert J. Goldberg, Joel M. Gore, Joseph S. Alpert, Voula Osganian, Jacques de Groot, Jurgen Bade, Zuoyao Chen, David Frid, James E. Dalen
Journal: New England Journal of Medicine (1991)

Cardiogenic shock resulting from acute myocardial infarction is a serious complication with a high mortality rate, but little is known about whether its incidence or outcome has changed over time. As part of an ongoing population-based study of acute myocardial infarction, we examined trends over time in the incidence and mortality rate of cardiogenic shock after acute myocardial infarction.We studied 4762 patients with acute myocardial infarction who were admitted to 16 hospitals in the Worcester, Massachusetts, metropolitan area between 1975 and 1988. We determined the incidence of and short-term and long-term mortality due to cardiogenic shock in each of six years during this study period.The incidence of cardiogenic shock complicating acute myocardial infarction remained relatively constant, averaging 7.5 percent. Multivariate regression analysis that controlled for variables affecting incidence revealed significant though inconsistent temporal trends in the incidence of cardiogenic shock. As compared with the risk in 1975, the adjusted relative risk (with 95 percent confidence interval) was 0.83 (0.54 to 1.28) in 1978, 0.96 (0.63 to 1.48) in 1981, 0.68 (0.42 to 1.12) in 1984, 1.16 (0.70 to 1.92) in 1986, and 1.65 (0.99 to 2.77) in 1988. The overall in-hospital mortality rate among patients with cardiogenic shock was significantly higher than that among patients without this complication (77.7 percent vs. 13.5 percent, P less than 0.001). The in-hospital mortality among the patients with shock did not improve between 1975 (73.7 percent) and 1988 (81.7 percent). Long-term survival during the 14-year follow-up period was significantly worse among patients who survived cardiogenic shock during hospitalization than among patients who did not have shock (P less than 0.001).The results of this observational, community-wide study suggest that neither the incidence nor the prognosis of cardiogenic shock resulting from acute myocardial infarction has improved over time. Both in-hospital and long-term survival remain poor for patients with this complication.
Tumor Location and Histological Type Related to Intratumoral Expression of 5-Fu Metabolizing Enzymes in Stage III Colon Cancer: a Multicenter, Prospective Cohort Study [B-Cast Study]
Authors: M. Ishiguro, E. Nakatani, K. Kotake, G. Nishimura, N. Tomita, W. Ichikawa, K. Takahashi, T. Watanabe, T. Furuhata, K. Kondo, M. Mori, Y. Kakeji, A. Kanazawa, M. Kobayashi, M. Okajima, I. Hyodo, S. Tanaka, K. Sugihara
Journal: Annals of Oncology (2014)