tbuckley/cabot-search huggingface dataset:
Expression of immunohistochemical markers chromogranin A, Ki-67, CD99, EGFR in resected pulmonary neuroendocrine tumors
Authors: Yanina Slavova, Dora Marinova, Vladimir Maksimov, Danail Petrov, Eluar Goranov, Vladimir Djambazov
Journal: European Respiratory Journal (2011)

Aim:  To evaluate the immunohistochemical expression of the markers Chromogranin A, Ki-67, CD99, EGFR in resected pulmonary neuroendocrine tumors (pNET).   Methods:  Surgically resected specimen from 49 patients (men-31, 63.3%, women–18, 36.7%) with pNETs were studied: typical carcinod (TC)-20 (40.8%), atypical carcinoid (AC)-7 (14.3%), small cell lung carcinoma (SCLC)-20 (40.8%), and large cell neuroendocrine carcinoma (LCNEC)-2 (4.1%). The histological type, pTNM stage and the immunohistochemical expression of Chromogranin A, Ki-67, CD99 and EGFR was evaluated.   Results:  The distribution in stages was as follows: TC & AC-I stage-20 (74.1%), II-5 (18.5%), IIIA-2 (7.4%); SCLC-IB-3 (15%), II-4 (20%), IIIA-9 (45%), IIIB & IV-4 (20%); LCNEC were in II stage. Neuroendocrine differentiation proved in all tumors by  Chromogranin A . The mean values of  Ki-67  were: TC-1.7%, AC–11.7%, SCLC–75.8%, LCNEC–63.5% (p=0.001).  CD99  expression was proved in 22 (44.9%) of the cases (in 9 – it was expressed in 100% of the tumor cells). 11 (50%) of them were carcinoid tumors, 9 (40%) – SCLC, 2– LCNEC. 40% of all TC&AC express CD99. 45% of SCLC express CD99. In AC CD99 positive cases, Ki-67 was 22.3%, and in AC CD99 negative cases Ki-67 was 3.75% (p=0.008). From 49 cases in 10 (19.7%) an  EGFR  expression was observed – TC&AC-4 (20.4% of all carcinoids), SCLC-5 (25% of all SCLC), and LCNEC-1. In 3 of the carcinoid tumors and in 4 of the SCLC 100% of the tumor cells express the marker while in the remaining tumors it was clonal.   Conclusion:  The CD99 expression correlates statisticaly significant with high Ki-67 index in AC. EGFR expressing NETs may be candidates for treatment with tyrosine – kinase inhibitors.
Lenograstim prevents morbidity from intensive induction chemotherapy in the treatment of inflammatory breast cancer.
Authors: B Chevallier, P Chollet, Y Merrouche, H Roche, P Fumoleau, P Kerbrat, J Y Genot, P Fargeot, J P Olivier, C Fizames
Journal: Journal of Clinical Oncology (1995)

PURPOSE To compare the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rHuG-CSF) versus its inert vehicle in patients with unilateral nonmetastatic inflammatory breast cancer treated with fluorouracil, epirubicin, and cyclophosphamide high-dose (FEC-HD) neoadjuvant chemotherapy. PATIENTS AND METHODS One hundred twenty patients have been enrolled by nine French centers in this double-blind, parallel-group, vehicle-controlled study to compare at each cycle subcutaneous lenograstim (5 micrograms/kg/d) with placebo given from day 6 to day 15 after the induction chemotherapy (day 1 to day 4, fluorouracil 750 mg/m2 continuous intravenous [IV] infusion; day 2 to day 4, epirubicin 35 mg/m2 and cyclophosphamide 400 mg/m2 both IV push). Four cycles were planned every 3 weeks before locoregional treatment. Patients with febrile neutropenia remained blinded for the subsequent cycles. RESULTS Lenograstim significantly reduced the duration of neutropenia at less than 0.5 x 10(9)/L and less than 1 x 10(9)/L to a median duration of 2 and 3 days, respectively, as compared with 5 and 7 days in the placebo group. This translated into a statistically significant reduced incidence of microbiologically documented infections, and a decreased need for rehospitalizations for infectious events and antibiotic use. Clinical objective tumor response rate observed after four cycles was 89.6% and 93%, respectively, in the placebo and treated groups. Mild transient bone and injection-site pain, myelemia, and hyperleukocytosis were the most frequently reported adverse events associated with lenograstim. CONCLUSION Lenograstim is safe and effective to reduce morbidity associated with FEC-HD neoadjuvant chemotherapy in inflammatory breast cancer. Response rate is not affected.
18F-fluorodeoxyglucose (18FDG) PET pulmonary imaging:comparative methodology in COPD patients
Authors: Gourab Choudhury, Alison Fletcher, Martin Connell, Tim Clark, Susie Ferguson, Roberto Rabinovich, Nick Weir, Brandon Whitcher, Iain Kilty, William Vennart, Edwin J.R. van Beek, William MacNee
Journal: European Respiratory Journal (2014)

Introduction: 18FDG PET/CT imaging may be a useful tool to study lung inflammation in COPD; however the optimal protocol for this imaging biomarker has yet to be established.  Method:We aimed to develop a combined 18FDG-PET/CT imaging protocol optimised to quantify lung inflammation. 6 patients with moderate-severe COPD underwent dynamic 18FDG-PET imaging combined with serial blood sampling (arterial and venous) to determine the localised plasma activity time curve. High resolution CT(HRCT) was utilised to segment the lung and determine areas of emphysema. 3 sets of comparative input functions were analysed (arterial, venous and image derived arterial input function). 18FDG kinetics was fitted using the Patlak method.  Results:Similar results were obtained using time activity curves from all 3 input functions. The arterial input was always found to be slightly higher than the others (Fig.1 Left). Patlak analysis of the time-activity curves for each of the CT derived lung lobes allowed generation of images of slope (influx constant Ki) and intercept (initial volume of distribution)(Fig.1 Right). Acquisition of HRCT co-registered to FDG-PET allows precise demarcation and quantification of FDG in emphysematous areas of the lung. The reproducibility of the technique is currently being studied.  Conclusion:18FDG PET/CT imaging has the potential to be a non-invasive biomarker of lung inflammation in COPD.  (Funded by Pfizer Inc.)
Low Dose Inhaled Budesonide and Formoterol in Mild Persistent Asthma
Authors: PAUL M. O'BYRNE, PETER J. BARNES, ROBERTO RODRIGUEZ-ROISIN, EVA RUNNERSTROM, THOMAS SANDSTROM, KLAS SVENSSON, ANNE TATTERSFIELD
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The optimal treatment for mild asthma is uncertain. We assessed the effects of adding a long-acting inhaled beta-agonist, formoterol, to low doses of an inhaled corticosteroid, budesonide, for 1 yr in subjects with mild asthma, receiving no or only a small dose of inhaled corticosteroid. The 698 corticosteroid free patients (Group A) were assigned to twice daily treatment with 100 μ g budesonide, 100 μ g budesonide plus 4.5 μ g formoterol, or placebo. The 1,272 corticosteroid-treated patients (Group B) were assigned to twice daily treatment with 100 μ g budesonide, 100 μ g budesonide plus 4.5 μ g formoterol, 200 μ g budesonide, or 200 μ g budesonide plus 4.5 μ g formoterol. The main outcome variables were time to the first severe asthma exacerbation and poorly controlled asthma days. In Group A, budesonide alone reduced the risk for severe exacerbations by 60% and poorly controlled days by 48%; adding formoterol increased lung function with no change in other end points. By contrast, in Group B, adding formoterol reduced the risk for the first severe exacerbation and for poorly controlled days by 43 and 30%, respectively. Thus, in corticosteroid-free patients, low dose inhaled budesonide alone reduced severe exacerbations and improved asthma control, and in patients already receiving inhaled corticosteroid, adding formoterol was more effective than doubling the corticosteroid dose.
P-319 Angiogenesis evaluation in locally advanced colo-rectal and gastric cancers by probe-based Confocal Laser Endomicroscopy (pCLE)
Authors: R. Cannizzaro, V. De Re, P. Spessotto, M. Mongiat, S. Maiero, E. Orzes, M. Fornasarig, A. Buonadonna, A. De Paoli, G. Bertola, V. Canzonieri
Journal: Annals of Oncology (2015)
GP should have seen child who was being starved within 48 hours of contact, says tribunal
Authors: C. Dyer
Journal: BMJ (2015)

A GP failed to take adequate action over concerns about a 4 year old boy who was being starved by his mother and stepfather but is nevertheless fit to practise, a regulatory tribunal has decided.

Mohammad Pathan’s failure to ensure that he saw Daniel Pelka within 48 hours after a telephone call in January 2012 from the worried deputy head of the boy’s school amounted to misconduct, a Medical Practitioners Tribunal Service panel concluded. The GP told the deputy head to ask Daniel’s mother to bring him to the surgery but failed to realise that she might not comply …
High frequency of benign mediastinal uptake of gallium-67 after completion of chemotherapy in children with high-grade non-Hodgkin's lymphoma.
Authors: N Peylan-Ramu, T B Haddy, E Jones, K Horvath, M A Adde, I T Magrath
Journal: Journal of Clinical Oncology (1989)

We observed increased gallium-67 uptake in the mediastinum after completion of chemotherapy in 10 of 62 patients with non-Hodgkin's lymphoma. All 10 were under 15 years of age, yielding a frequency of 43% in this age group. The interval between cessation of chemotherapy and the development of increased gallium-67 uptake ranged from 1 to 8 months, and the abnormality persisted for 2 to 59 months. Serial chest x-rays were performed in all patients, and four of the 10 had transient widening of the mediastinum that remained within normal limits for the children's ages. Three patients had chest computed tomographic (CT) scans at the time of increased gallium-67 uptake, and one of the three had serial scans that showed a mediastinal mass consistent with thymic enlargement. All of the patients were asymptomatic and none were biopsied. All 10 remained well, with a mean follow-up of 52.5 months. The phenomenon we describe is probably due to "rebound" thymic hyperplasia, which is a benign and transient condition. We conclude that abnormal mediastinal gallium-67 uptake after completion of chemotherapy is likely to be benign and transient if the patients are young, have small non-cleaved-cell histology, are without other evidence of lymphoma recurrence, and do not have initial mediastinal involvement. Progressive widening of the mediastinum on chest x-ray is cause for suspicion and requires further evaluation. Serum lactate dehydrogenase (LDH) levels may not be helpful in differentiating a benign from a malignant process.
Iso-Osmotic Bowel Preparation Improves the Accuracy of Iliac Artery Colour Flow Duplex Examination
Authors: M S Whiteley, A D Fox, R A Harris, M Horrocks
Journal: Journal of the Royal Society of Medicine (1995)

Colour flow duplex ultrasonography is currently the non-invasive method of choice for investigating the iliac arteries. However it is only 84–92% sensitive in the best hands when compared with biplanar angiography. Bowel gas and faeces overlying the iliac arteries obscure the vessels and prevent a good ultrasound image. We have previously shown that preparation of the bowel with an iso-osmotic bowel preparation (Klean Prep) improves the clarity of duplex image of the iliac arteries. This is caused by a volume effect which flushes out gas and faeces, leaving a fluid-filled bowel transparent to ultrasound. The aim of this study was to investigate whether this enhanced image increased the diagnostic accuracy of duplex examination. We performed iliac duplex examinations on 56 patients with clinically suspected iliac artery disease, initially with the normal preparation of starving the patients for 12 h and subsequently after preparation by Klean Prep. The results from each investigation were compared with the gold standard of biplanar intra-arterial digital substraction angiography. The use of iso-osmotic bowel preparation (Klean Prep) significantly improved the accuracy of iliac duplex ultrasonography over preparation by 12 h starvation, when compared with biplanar angiography.
Abstract 2671: Inhibition of Cytochrome P450 2C9 with Trans-Guidewire Therapy Dramatically Reduces Ischemia Reperfusion Injury in a Porcine Model of Acute Myocardial Infarction
Authors: Peter E Ruchin, Cameron Densem, Casidy Hallsten, David J Granville, Anouf Nehmatallah, Betty B Cai, Amin Aminbakhsh, Ken Gin, Karim Qayumi, Jaap N Hamburger
Journal: Circulation (2008)
Resistive breathing induces matrix metalloproteinases-9 and -12 expression in the lung
Authors: Dimitrios Toumpanakis, Olga Noussia, Ioanna Sigala, Tatianna Michailidou, Vasso Karavana, Charalampos Roussos, Stamatios Theocharis, Theodoros Vassilakopoulos
Journal: European Respiratory Journal (2012)

Resistive breathing (RB), encountered in obstructive airway diseases, is associated with large negative intrathoracic pressures and has been recently shown to induce acute lung injury and inflammation. Matrix metalloproteinases (MMP)-9 and -12, implicated in the pathogenesis of both asthma and COPD, are upregulated by inflammation and by mechanical stress per se. We hypothesized that RB induces MMP9 and -12 expression and activity in the lung.  Anesthetized, tracheostomised rats were breathing through a 2-way valve. The inspiratory line was connected to a resistance setting peak tracheal pressure at 50% of maximum (RB). Quietly breathing animals served as controls. After 3 and 6hrs of RB, bronchoalveolar lavage (BAL) was performed to measure cell count and cytokine levels by ELISA. Lung injury was evaluated by histology. MMP9 lung levels were measured by zymography and immunohistochemistry (IHC). MMP12 was detected by IHC. Alveolar macrophages from normal rats were incubated with BAL fluid from rats that underwent RB. MMP9 activity was measured in cell supernatants by zymography.  After 3 and 6hrs of RB, lung injury was detected by histology. Increased numbers of alveolar macrophages and neutrophils (p  In previously healthy rats, RB resulted in increased MMP9 and -12 expression in the lung.
Foreign body aspirations from the perspective of our clinic
Authors: Asli Gül Akgül, Aykut Eliçora, Serife Tuba Liman, Salih Topçu, Alparslan Kus, Seymur Salih Mehmetoglu, Serkan Özbay, Hüseyin Fatih Sezer, Zeynep Seda Uyar
Journal: European Respiratory Journal (2013)

Introduction: Foreign body aspiration (FBA) is a life threating emergency at all ages but especially in childhood. Although wheezing, sudden cough and decreased breath sounds on one side consist the clinical triad, symptoms can be several due to the type, size and location of the foreign body. We are presenting FBAs admitted to our clinic in last 8 years.  Material-Method: 271 FBA suspected patients (ages between 2 months - 74 years-old, with 134 male and 182 under 2 years-old), admitted to Kocaeli University pediatric emergency and thoracic surgery clinics between 2005 - 2012. Rigid bronchoscopy performed to all under general anesthesia in theatre room. 47 patients were admitted in first 24 hours, and remaining after 24 hours. Physical examination, chest x-ray were performed to all and thorax CT to 32. FBA diagnosed in 226 patients. Foreign bodies removed were divided into two groups. Foods most commonly hazelnut, peanut, corn, sunflower seed were grouped as organic foreign bodies and needle, buckle, pen cap, pen spring, bead, cigarette filter etc. were inorganic. Organics were removed from 165 patients. Pneumothorax and subcutaneous emphysema which required drainage occured in two cases.  Discussion: FBA can be prevented, and the associated morbidity and mortality can be significantly reduced by educating the public regarding its potential dangers. All patients should be evaluated radiologically and bronchoscophy should be performed when it is not possible to rule out foreign body aspiration.
Treatment of advanced head and neck cancer with induction chemotherapy followed by chemoradiotherapy with reduced radiation dose
Authors: D. Gustin, D. J. Haraf, K. Stenson, E. Cohen, F. Rosen, A. Argiris, B. E. Brockstein, M. E. Witt, A. Dekker, E. E. Vokes
Journal: Journal of Clinical Oncology (2004)

5546 Background: In a previous study by our group, induction chemotherapy (CT) with weekly carboplatin (C) [AUC=2] and paclitaxel (T) [135 mg/m2] x 6 weeks followed by chemoradiotherapy with the TFHX regimen (T, 5-FU, hydroxyurea and bid XRT) resulted in an 82% response rate (RR) after induction, 100% RR after completion of all treatment, 77% overall 2-year survival and only 3 (14%) of 22 patients with post treatment neck dissections (LND) displaying residual tumor [Clin Cancer Res 9(16):5936–5943, 2003]. In an attempt to decrease toxicity without compromising local control, a similar cohort of patients was treated with a lower dose of radiation to sites of potential microscopic disease. Methods: Between 1/01 and 8/02, 91 patients (65 males/26 females) were entered on a phase II study and were treated with a slightly modified induction CT regimen consisting of two (28-day) cycles of C (AUC=6) and T (100mg/m2/wk x 3 weeks) followed by five cycles of TFHX. The dose of XRT was reduced from 75, 54 and 39 Gy to 72, 51 and 36 Gy for gross (GD), high risk microscopic (HRM) and low risk microscopic (LRM) disease, respectively. Results: 92% of patients had stage IV disease (71% N2-N3 disease). RR following induction CT and completion of TFHX were 82% (CR=26%, PR=56%) and 98% (CR=78%, PR+20%), respectively. Grade 3/4 mucositis and dermatitis occurred in 66% and 27% of patients (75% & 45% in the previous study). Chronic toxicity assessment (e.g. dependence on G-tube for nourishment) awaits further maturation of the data. At a median follow-up of 19.8 months the 2-year overall and progression free survival were 73 % and 69%, respectively. LND were performed in 32 patients with 10 (31%) surgical specimens containing residual tumor. Conclusions: Reductions in XRT dose as those outlined in this study have resulted in similar RR and overall survival as well as lesser acute locoregional toxicity to that seen in prior studies by our group. The larger proportion of residual tumor in LND specimens suggests that we may have now reached a threshold where further decreases in XRT may not be warranted. Changes in the schedule of induction CT may also have contributed to these findings. No significant financial relationships to disclose.
Airway obstruction by GOLD and ATS/ERS2005 criteria in Caucasian American pulmonary laboratory patients using NHANESIII and ERS/GLI12 prediction equations
Authors: Olinto Linares-Perdomo, David Collingridge, Dean Sorenson, Matthew Hegewald, Denitza Blagev, Robert L. Jensen, John Hankinson, Alan Morris
Journal: European Respiratory Journal (2014)

RATIONALE: 

GOLD and ATS/ERS2005 use different criteria for diagnosis and severity. NHANESIII and ERS/GLI Prediction Equations produce different lower limits of normal.

METHODS: 

12,239 reproducible and acceptable spirograms (10 to 95 year old Caucasian males and females from 2001 to 2013). We examined differences in obstruction diagnosis and classification between GOLD and ATS/ERS2005 criteria by patient age, using NHANESIII and the ERS/GLI12 prediction equations (e.g., 100% x [number of 36 year olds with obstruction by GOLD - number of 36 year olds with obstruction by ATS/ERS2005] / [number of 36 year olds]).

RESULTS: 

GOLD classified more patients with obstruction than ATS/ERS2005. Differences were almost identical with NHANESIII and ERS/GLI12 prediction equations and increased with age (Figure 1). 626 (5.1%) of patients with obstruction by GOLD but not ATS/ERS2005 had mild and 614 (4.7%) had ≥moderate obstruction (by GOLD) (Figure 1).

CONCLUSION: 

Diagnosis and classification of airway obstruction in Caucasian Americans is influenced by interpretive criteria (GOLD vs. ATS/ERS2012), but not by the NHANESIII and the ERS/GLI12 prediction equations.

![Figure][1] 



Figure 1:Upper panel: Obstruction diagnosis using GOLD versus ATS/ERS criteria with NHANESIII and ERS/GLI predictions. Lower panel: % of patients by age obstructed with GOLD but not obstructed with ATS/ERS-2005.

 [1]: pending:yes
Amphiphilic drugs as surfactants to fabricate excipient-free stable nanodispersions of hydrophobic drugs for cancer chemotherapy
Authors: Shiqi Hu, Eunhye Lee, Chi Wang, Jinqiang Wang, Zhuxian Zhou, Yixian Li, Xiaoyi Li, Jianbin Tang, Don Haeng Lee, Xiangrui Liu, Youqing Shen
Journal: Journal of Controlled Release (2015)
Long-term in vivo expression of trastuzumab following intramuscular electrotransfer of the encoding DNA in mice
Authors: Kevin Hollevoet, Nick Geukens, Greetje Vande Velde, Paul Declerck
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts In vivo antibody expression is at crossroads between monoclonal antibody (mAb) and gene therapy. Following a single intramuscular injection of the DNA that encodes a therapeutic mAb, the muscle is turned into a ‘bioreactor’, resulting in prolonged mAb secretion in circulation
Phase II study of lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase 1 and 2 (Her2/Neu) in patients (pts) with advanced biliary tree cancer (BTC) or hepatocellular cancer (HCC). A California Consortium (CCC-P) Trial
Authors: R. K. Ramanathan, C. P. Belani, D. A. Singh, M. Tanaka, H. J. Lenz, Y. Yen, H. L. Kindler, S. Iqbal, J. Longmate, D. R. Gandara
Journal: Journal of Clinical Oncology (2006)

4010 Background: Advanced BTC (gallbladder, bile duct) and HCC respond poorly to systemic chemotherapy. Lapatinib is an oral inhibitor of EGFR and Her/2-neu with evidence of activity in a number of tumor types. Both BTC and HCC overexpress EGFR 1 and 2. In addition, Her2/neu somatic mutations have been reported in HCC, and may predict response to EGFR targeted agents (Bekaii-Saab et al, A 4037, ASCO 2005). This trial conducted by the CCC-P and Univ. Chicago, is designed to determine the efficacy of lapatinib in BTC and HCC pts. Methods: A two-stage design is utilized and pts are stratified by tumor type (BTC or HCC); the study has a 90% power to detect a true response rate ≥20%. Two initial groups of 17 patients for BTC and HCC were accrued; one response from each was required to proceed with accrual to a total of 37 patients in each group. Adequate hematologic, renal, and hepatic function is required. Eligible pts are in Child A group and have ECOG PS of 0–2. One prior treatment regimen is allowed. Lapatinib dose is 1,500 mg/d orally without interruption. One cycle is 28 days and radiological assessment is done every 8 weeks. Results: 49 pts have been accrued (BTC 19 and HCC 30). Pt Characteristics: Male 59%, ECOG PS 0 (18 pts), ECOG PS 1 (22 pts). Median age 66 yrs (range19–82). Median cycles 2 (range 1–12). Grade 3/4 toxicity was noted in 19 pts and included fatigue in 4 pts, elevation of liver enzymes in 4 pts and diarrhea in 2 pts. Nausea, vomiting, rash, anemia and thrombocytopenia were noted in 1 pt each. There was no evidence of cardiac dysfunction. In 17 evaulable pts with BTC, no responses were observed, 5 had stable disease (SD). Among the first 17 pts with HCC, 2 confirmed partial responses have been recorded. In addition 8 pts have SD. The progression free survival is 1.8 mo for both BTC and HCC. Tumor and blood specimens are being analyzed for expression of EGFR, HER-2/neu, status of downstream signal pathway molecules, and correlation to response. Conclusions: Lapatinib is well-tolerated. No activity in BTC was noted and that cohort is closed. Lapatinib activity in HCC is encouraging, and study is close to completion. Source of support: NCI-NO1-CM-57018–16. [Table: see text]