tbuckley/cabot-search huggingface dataset:
Varying recurrence rates and risk factors associated with different definitions of local recurrence in patients with surgically resected stage I non-small cell lung cancer
Authors: L. N. Medford-Davis, J. Varlotto, A. Recht, J. C. Flickinger, M. M. DeCamp
Journal: Journal of Clinical Oncology (2009)

7583 Background: To examine the effects of different definitions of local recurrence on the reported patterns of failure and associated risk factors in patients undergoing potentially curative resection of Stage I non-small cell lung cancer (NSCLC). Methods: The study included 306 consecutive patients treated from 2000–2005 without radiotherapy. Local recurrence was defined as either: “radiation” (i.e., recurrences confined to the post-operative radiotherapy fields used in the Phase III trial of adjuvant radiotherapy by Trodella et al) (LRR), including the bronchial stump, staple line, the ipsilateral hilum, and ipsilateral mediastinum; or “comprehensive” (LRC), including these sites plus the ipsilateral lung and contralateral mediastinal and hilar nodes. Results: The median follow-up was 33 months. Proportions of LRC and LRR at 2, 3 and 5 years were 14%, 21% and 29%; and 7%, 12%, and 16%, respectively. Significant risk factors for LRC on multivariable analysis were diabetes, lymphatic vascular invasion and tumor size; significant factors for LRR were resection of less than a lobe and lymphatic vascular invasion. Distant (non-local) relapse proportions using these definitions at 2, 3 and 5 years were 10%, 12%, and 18%; and 14%, 19%, and 29%, respectively. Significant risk factors for distant failure were histology when using the LRC definitions and tumor size using the LRR definition. Conclusions: Local recurrence increased nearly two-fold when a broad definition was used, rather than a narrow one. The definition also affected which factors were significantly associated with both local and distant failure on multivariate analysis. Comparable definitions must be used when analyzing different series. No significant financial relationships to disclose.
Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST): A meta-analyis based on 1,640 patients (pts)
Authors: M. M. Van Glabbeke, K. Owzar, C. Rankin, J. Simes, J. Crowley
Journal: Journal of Clinical Oncology (2007)

10004 Background: The MetaGIST project aims to further explore the data of the two randomized studies comparing two doses of imatinib (400 mg od vs bid) for the treatment of GIST: EORTC/ISG/AGITG 62005 (EU-AUS) and SWOG/CALGB/NCI-C/ECOG/ICAS S0033 (US-CDN). Methods: End-points were progression free (PFS) and overall survival (OS). Investigated cofactors included age, sex, performance status (PS), primary tumor site, time from diagnosis, prior therapies, baseline biology, and KIT / PDGFRa mutations for a subset of 772 pts (47%). The logrank test (stratified) and the Cox multivariate model with interaction terms were used for the analysis. Results: The median follow-up was 45 months. A small but significant PFS advantage was documented for the high dose arm, consistently in both studies. OS was identical in the two arms (see table ). Males and pts with a poor PS, GIST from bowel origin, baseline low hemoglobin and high neutrophils counts (ANC) had a significant worse PFS (multivariate analysis); these factors are consistent between studies. In pts analyzed for mutations, wild type pts (HR=1.56), KIT exon 9 mutants (HR=2.17) and pts with other mutations (HR=2.56) had a worse prognosis than KIT exon 11 mutants (univariate analysis); all 3 factors remained in the multivariate model. The US-CDN study included significantly (P&lt;0.01) more females, more GIST from bowel or stomach origin, less KIT exon 9 mutants and pts with a lower baseline ANC. In KIT exon 9 mutants, the PFS advantage with high dose imatinib previously reported in the EU- AUS study was not confirmed in the US-CDN dataset, but remains significant in the pooled dataset. The interaction between dose effect on PFS and prognostic factors was siginficant for KIT exon 9 mutations but not for other factors. Conclusions: This analysis confirms a small PFS advantage of high dose imatinib, essentially amongst KIT exon 9 mutants, but no OS advantage. Heterogeneity between the two studies is being further explored. [Table: see text] [Table: see text]
Medical hypnosis as a tool to acclimatize children to non-invasive positive pressure ventilation: A pilot study
Authors: Vincent Delord, Sonia Khirani, Adriana Ramirez, Erick Louis Joseph, Clotilde Gambier, Maryse Belson, Francis Gajan, Brigitte Fauroux
Journal: European Respiratory Journal (2013)

Introduction   Patient cooperation is crucial for success of non-invasive positive pressure ventilation (NPPV).   Objectives   This study evaluated the efficacy of medical hypnosis to reduce the anticipatory anxiety and the acclimatization time in children candidates for long-term NPPV.   Methods   Medical hypnosis was performed by a trained nurse. The acclimatization time and long-term compliance with NPPV were evaluated.   Results   Hypnosis was performed in 9 children, aged 2 to 15 years old; 7 children with a high level of anticipatory anxiety because of a tracheotomy since birth (2 patients), a history of maxillofacial surgery (2 patients), severe dyspnea due to lung disease (2 patients), morbid obesity and depression (1 patient), and 2 children with obstructive sleep apnea who failed standard NPPV initiation. The hypnosis techniques were based on distraction in the youngest patient and indirect or direct hypnotic suggestions in the older children, in order to obtain a progressive psycho-corporal relaxation. All the patients accepted the interface and the NPPV after the first hypnosis session. A median of three sessions was needed for overnight (> 6 hours) NPPV acceptance. The 6-months compliance with NPPV was excellent with a median use of 7.5 hours/night.   Conclusion   Medical hypnosis is a very effective, safe, non-invasive, and cheap tool for reducing the anticipatory distress and acclimatizing time for NPPV. This therapy is particularly useful in children with traumatic experiences such as a tracheotomy or facial surgical procedures.
Metabolic syndrome, diabetes mellitus, and the subsequent development of prostate cancer
Authors: Y. R. Lawrence, O. Morag, V. Boyko, M. Benderly, U. Goldbourt, M. Barchana, S. Behar, I. Wolf, A. P. Dicker, R. Catane
Journal: Journal of Clinical Oncology (2009)

5158 Background: The lifetime risk of an American man developing prostate cancer (PC) is one in six. Metabolic syndrome (MS) is a cluster of medical disorders (hypertension, dyslipidaemia, hyperglycaemia, obesity) associated with the subsequent development of diabetes mellitus (DM). DM and MS afflict 11% and 22% of US adults respectively. MS and DM are associated with disturbed lipid homeostasis, and hypogonadism. DM and MS predispose to the development of gastrointestinal and endometrial cancer. DM and MS's influence on PC is less clear; some studies have suggested that whereas DM inhibits PC, MS promotes PC development. Methods: The Bezafibrate Infarction Prevention study was a randomized trial of fibrate therapy for the secondary prevention of ischemic heart disease. Between 1990–2 15524 men and women with ischemic heart disease were screened, of whom 3090 entered the trial. 81% were male. Participants were divided into three groups according to baseline parameters: (A) those with neither MS nor DM, (B) those with MS but no DM, (C) those with DM (with or without MS). MS was defined according to ATPIII guidelines. DM was defined by medical history or fasting glucose &gt; 125 mg/dL. Follow-up for PC incidence and all-cause mortality was obtained through the Israeli cancer registry and the Ministry of the Interior respectively. Analysis accounts for differences in age and non-cancer-related-mortality between groups. Ethics approval was obtained. Results: 1350 participants were excluded due to missing data or previous cancer diagnosis, leaving 11,541 men. Mean age at enrollment 61 years (45–74). Median follow-up was 12 years. There were 6119 (53%), 3,376 (29%), and 2,046 (18%) participants in groups A, B and C respectively. Overall there were 459 cases of PC; 298, 123 and 48 in groups A, B and C. The age adjusted PC rates were 4.30, 3.61 and 2.55 per 1,000 patient years in groups A, B and C respectively (A vs C p = 0.003). Data were also analyzed examining PC incidence as a function of ‘number of components of MS present’ after pooling groups A, B and C. Relative risk of developing PC was 1.00, 0.92, 0.90, 0.69, 0.71, and 0.33 for 0, 1, 2, 3, 4, and 5 components respectively. Conclusions: A baseline diagnosis of DM (highly significant) or MS (trend) was associated with a decreased prostate cancer rate over the subsequent 12 years. No significant financial relationships to disclose.
Role of Galectin-3 in the activation of p-ERK and in resistance to radiotherapy in glioblastoma through the activation of p-ERK independent of Ras activity
Authors: A. R. El-Jawahri, T. Lautenschlaeger, D. Patel, A. Chakravarti
Journal: Journal of Clinical Oncology (2009)

11073 Background: There has been a growing interest in investigating the molecular mechanisms leading to treatment resistance in glioblastoma (GBM). The MAPK pathway has been shown to be involved in mediating treatment resistance. Galectin-3 (Gal3) is commonly overexpressed in astrocytic tumors of the brain and has been associated with adverse clinical outcomes. We investigated the role and mechanisms of Gal3 in mediating treatment resistance in GBM through modulating the MAPK pathway. Methods: We investigated Gal3 expression in GBM cell lines (U87, LN18, LN229). We created stable Gal3 knockdown cell lines (Gal3KD), ERK-knockdown (lentiviral shRNA) and constitutively active MEK(MEK2DD plasmid obtained from Dr. Brugge) cell lines. We then evaluated the radiosensitivity, apoptosis, and cell viability of control cell lines treated by non-targeting (NT) vectors as compared to Gal3KD, ERKKD and MEK2DD using clonogenic survival, Annexin V/PI apoptosis, COMET, and cell cycle assays. Signaling cascades were evaluated using Western blot and a GTP-ras pull down assay. Gal3 was also transiently knocked down in MEK2DD and NT cell lines and signaling cascades were analyzed using western blotting. Gal3 binding interactions were identified using co-immunoprecipitation. Results: Gal3 expression was induced in all GBM cell lines following irradiation. Gal3KD showed increased radiosensitivity similar to ERKKD as compared to controls with decreased clonogenic survival, increased DNA damage, increased apoptosis, and increased cell cycle arrest in G1 and G2, while MEK2DD showed enhanced radioresistance. Gal3KD showed reduced p-ERK at baseline followed by a minimal induction of p-ERK with irradiation as compared to controls which have a high level of p-ERK. Overall p-Akt, ERK and Ras-GTP levels were equivalent in Gal3KD and controls. When Gal3 was transiently knocked down in MEK2DD cell line, p-ERK was drastically reduced similar to controls. Gal3 co-immunoprecipitated with ERK. Conclusions: Our results suggest a possible direct novel interaction between Gal3 and ERK in GBMs that is essential for the expression of p-ERK and mediating treatment resistance in GBMs. No significant financial relationships to disclose.
Linoleic Acid Inhibition of Naturally Occurring Lymphocytotoxicity to Breast Cancer-Derived Cells Measured by a Chromium-51 Release Assay&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Curt P. Samlaska
 6
Journal: JNCI Journal of the National Cancer Institute (1979)

Long-chain unsaturated free fatty acids have been shown to inhibit the immune responses of lymphocytes in vivo and in transformation and macrophage inhibition factor assays in vitro. The purpose of this study was to test the effect of linoleic acid on naturally occurring lymphocytotoxicity in a 51Cr release microcytotoxicity assay with the use of a human breast carcinoma cell line (AlAb) as source of the target cells. In the presence of increasing concentrations of linoleic acid, a linear decrease in lymphocytotoxicity was observed with complete inhibition at concentrations of 0.05-0.07 mg/ml. Concentrations of linoleic acid greater than 0.07 mg/ml resulted in nonspecific toxicity to target cells but not to lymphocytes as determined by trypan blue exclusion tests. When lymphocytes were pretreated with linoleic acid, washed, and then tested for cytotoxicity in the absence of linoleic acid, suppression of lymphocytotoxicity was still demonstrated. When leukocytes were depleted of macrophages, cytotoxicity in the absence of linoleic acid was enhanced 50-100%; complete inhibition of cytotoxicity was still observed at 0.05 mg linoleic acid/ml. When B- and T-cell populations were separated, each population showed typical decreases in lymphocytotoxicity in the presence of linoleic acid; however, the B-cell fraction (containing "null" cells) was two to three times more efficient at cell killing than was the T-cell fraction.
Response to: ‘Reporting of potential immunogenicity with biologic drugs: clarity and accuracy required’ by Moots<i>et al</i>: Table 1
Authors: Paul Emery, Jiří Vencovský, Jeehoon Ghil
Journal: Annals of the Rheumatic Diseases (2016)

We thank Dr Moots and colleagues1 for the questions regarding the immunogenicity results in our study.2

While it seems that there was much concern about the details of the methods and results of the immunogenicity data, the authors would like to reassure Dr Moots and colleagues that the presented data are valid and reliable and follow standard reporting procedures. We provide the following explanations and that they are helpful in this respect.

The proportion of patients who tested positive for antidrug antibodies (ADAs) at least once up to Week 24 was significantly lower in SB4 compared with the etanercept reference product (ETN) (2 patients (0.7%) in SB4 and 39 patients (13.1%) in ETN, p<0.001). Only one in the ETN group had neutralising capacity.2 The incidence of patients with positive ADA by titre up to Week 24 is presented in table 1. Almost all ADAs were transient, which is consistent with the previous studies with ETN.3 ,4 All patients were reported as positive only once throughout the …
BRAF Inhibition in Hairy Cell Leukemia: Multicentre Experience of 21 Patients Treated with Vemurafenib
Authors: Dietrich Sascha, Andreas Pircher, Mindaugas Andrulis, Elena Ellert, Frédéric Peyrade, Clemens-Martin Wendtner, George A Follows, Martin JS Dyer, Thomas Elter, Robert Zeiser, Anita Gaehler, Michael Herrmann, Michael Herold, Claire Dearden, Hanno Glimm, Michael Hallek, Anthony D Ho, Michael Steurer, Thorsten Zenz
Journal: Blood (2014)
Abstract 13426: Diabetes Severity is Associated with High Risk Plaque by Coronary CT Angiography: The FACTOR-64 Trial
Authors: George M Cater, Eunice Yang, Christopher T Sibley, Marcelo S Nacif, Boaz Rosen, Kyle D Balling, Heidi T May, Jeffery L Anderson, Donald L Lappe, Joao A Lima, David A Bluemke, Joseph B Muhlestein
Journal: Circulation (2012)

PURPOSE: Diabetes mellitus (DM) patients are at high risk for coronary artery disease (CAD), but noninvasive measurement of CAD extent and severity has not previously been available. Non-calcified ...
Hyperpigmented Reticulated Patch in an Older Man
Authors: Edward Bae, Jeffrey M. Cohen, Sarah C. Grudberg
Journal: JAMA (2016)

A 67-year-old man receiving rituximab for membranous nephropathy presented with volume overload and a hyperpigmented, gray-brown patch on his mid and lower back. He reported long-term use of a heating pad for chronic back pain but denied experiencing burns or thermal trauma. What would you do next?
Dendritic cell-based vaccination in combination with gemcitabine/S-1 in patients with advanced pancreatic cancer
Authors: M. Okamoto, S. Yusa, K. Shimamura, T. Ogawa, T. Tomoda
Journal: Journal of Clinical Oncology (2009)

3037 Background: Pancreatic cancer has a poor prognosis. Tumor-specific cytotoxic T lymphocytes (CTLs) can be activated in vivo by dendritic cell (DC)-based vaccination. However, clinical responses to the immunotherapy with DC vaccination have only been observed in a minority of patients with solid cancer. Combination with other treatment modalities such as chemotherapy may overcome immunoresistance of cancer cells. It has been shown previously that gemcitabine as well as S-1 sensitises human pancreatic carcinoma cells against CTL-mediated lysis. In the current study, the clinical efficacy of the DC vaccine pulsed with the peptide derived from pancreatic cancer-associated antigen in combination with gemcitabine/S-1 has been evaluated in the patients with advanced, inoperable pancreatic cancer. Methods: Thirteen patients with advanced, inoperable pancreatic cancer refractory to standard treatment were entered the study. DCs that were generated from CD14+ monocytes from leukapheresis by 6-day cultivation with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-4 were matured by OK-432, a streptococcal agent, and were pulsed with the pancreatic cancer-associated antigen. These DCs (1 x 107) were intradermally administered 5 times at 14-day intervals concomitantly combined with gemcitabine and/or S-1. Results: Of the 13 patients, complete response (CR) was observed in 2 (15.4%), partial response (PR) in 7 (54.8%), stable disease (SD) in 2 (15.4%), progressive disease (PD) in 2 (15.4%). Response rate was 69.2%. Survival rate, quality of life, and performance status were markedly increased. Severe side effects of more than grade 3 that were assessed in accordance with NCI-Common Toxicity Criteria v.2.0, were not observed. Conclusions: It was strongly suggested that the DC vaccination pulsed with cancer associated-peptid in combination with gemcitabine and/or S-1 was safety and effective in the patients with the inoperable pancreatic cancer refractory to standard treatment. No significant financial relationships to disclose.
Association Of Stringed Response and Immunoparesis Normalization After Bortezomib-Based Therapy Is Related To Better Outcomes In Multiple Myeloma
Authors: Marcio M Andrade Sr., Ilda Murillo-Florez, Anel Montes-Limon, Beatriz de Rueda, Jose-Maria Grasa, Pilar Giraldo
Journal: Blood (2013)
Contrast-enhanced harmonic endoscopic ultrasonography with time–intensity curve analysis for intraductal papillary mucinous neoplasms of the pancreas
Authors: Naoki Yamamoto, Hironari Kato, Takeshi Tomoda, Kazuyuki Matsumoto, Ichiro Sakakihara, Yasuhiro Noma, Shigeru Horiguchi, Ryo Harada, Koichiro Tsutsumi, Keisuke Hori, Takehiro Tanaka, Hiroyuki Okada, Kazuh de Yamamoto
Journal: Endoscopy (2015)

<b>Background and study aims:</b> Preoperative diagnosis of the pathological grade of intraductal papillary mucinous neoplasms (IPMNs) is difficult. This study aimed to evaluate the accuracy of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with time – intensity curve analysis in differentiating between low or intermediate grade dysplasia (LGD/IGD) and high grade dysplasia or invasive carcinoma (HGD/invasive carcinoma) in IPMNs and to assess correlation between the time – intensity curve parameters and tumor microvessel density. <b>Patients and methods:</b> Data from 30 patients with resected IPMNs (14 LGD/IGD, 16 HGD/invasive carcinoma) who underwent CH-EUS with time – intensity curve analysis were evaluated retrospectively. Time – intensity curve parameters and the microvessel density of the mural nodule were compared between the HGD/invasive carcinoma and LGD/IGD groups; the diagnostic accuracy of the time – intensity curve parameters was evaluated. <b>Results:</b> The echo intensity change and echo intensity reduction rate of the mural nodule, and the nodule/pancreatic parenchyma contrast ratio were significantly higher in the HGD/invasive carcinoma group than in the LGD/IGD group (<i>P</i> < 0.05); the accuracies of these parameters were 80 %, 86.7 %, and 93.3 %, respectively. The microvessel density of the mural nodule was significantly higher in the HGD/invasive carcinoma group (<i>P</i> = 0.002). There was a strong positive, linear correlation between the echo intensity change of the mural nodule and the microvessel density (<i>r</i> = 0.803, <i>P</i> < 0.001). <b>Conclusions:</b> CH-EUS with time – intensity curve analysis is potentially useful for quantitatively evaluating the blood flow of IPMN microvasculature, and for differentiating between HGD/invasive carcinoma and LGD/IGD.
First-line physician’s choice (PC1) or standard of care (SOC) then second-line PC2 chemotherapy (CT) in metastatic esophago-gastric adenocarcinoma (MEGA): BC Cancer Agency experience
Authors: K. S. Wilson, J. B. Barnett, K. Khoo, C. Kollmannsberger, A. Shah
Journal: Journal of Clinical Oncology (2007)

15158 Background: The BCCA GI Tumor Group supports 1 CT regimen for MEGA: weekly 5FU-cisplatin [FUC] (Shah, ASCO 1992, A530) for first line SOC CT. All other regimens (PC) require “undesignated” approval for public funding. Reasons for PC requests include prior CT, results of modern CT trials, and contra-indications to FUC. Objectives: to examine response, toxicity and survival in pts. receiving either first-line PC1 CT , or SOC and second line PC2 CT. Methods: BCCA Pharmacy records (Dec. 1999 to April 2006) were searched for PC MEGA pts, charts abstracted, database constructed and KM survival analyses undertaken. Treatment responses, serious toxicities and hospitalizations were recorded. Results: Demographic summary (N = 85): 32 esophageal (10 GEJ), 53 (62%) gastric primary, 61 M, 24 F, median age 56.2 (range 28.7 - 81.8) yrs., 68 Caucasian, 15 Asian, 2 Fijian descent, 55 stage M1 at diagnosis. Prior therapy: 14 CTRT, 3 adjuvant CT, 34 radical surgery. 50 pts received PC1 of whom 25, 9 and 2 received 2 nd , 3 rd and 4 th line CT respectively; of 35 SOC/PC2 pts, 35, 10 and 2 received 2 nd , 3 rd and 4 th line CT for a total of 133 patient-courses of PC (including 4 repeat FUC). Docetaxel and irinotecan regimens accounted for 34% and 36%, 5% and 55%, 16% and 32% of 1 st , 2 nd and 3 rd line PC CT regimens respectively. Partial responses were seen with SOC (11/35) and PC1 (6/50) [chi square p = 0.05]. Four responses were seen with 2 nd line CT (2 SOC/PC2, and 2 PC1). Grade 3+ toxicity rates: 19/49 (39%) and 6/36 (17%) with SOC and PC1 with initial CT (p = 0.02). There were 20 hospitalizations with PC and 2 with SOC CT (p = 0.02). Median follow-up time was 8.9 months. Survival analyses are presented below. Multivariate analysis results: primary site, SOC, gender, ethnicity, prior CT, p values were 0.15, 0.23, 0.23, 0.25 and 0.25 resp. Conclusions: Benefits and risks of non-SOC chemotherapy in MEGA need careful consideration before routine adoption as primary or subsequent therapy. [Table: see text] No significant financial relationships to disclose.
Ankle Range of Motion, Leg Pain, and Leg Edema Improvement in Patients With Venous Leg Ulcers
Authors: Joshua D. Fox, Katherine L. Baquerizo-Nole, Jeremy B. Freedman, Sophia Liu, Freya Van Driessche, Elizabeth Yim, Robert S. Kirsner
Journal: JAMA Dermatology (2016)

study was limited by its small sample size and short follow-up.Larger and longitudinal trials are warranted to further evaluate correlations between AROM, pain, edema, neuropathy, and wound healing.It is possible that interventions aimed to increase AROM may be additive to the care of VLU.