Stage III Non–Small-Cell Lung Cancer: Population-Based Patterns of Treatment in British Columbia, Canada

Introduction:Management of Stage III non–small-cell lung cancer (NSCLC) involves surgery, radiotherapy (RT), chemotherapy, and best supportive care. The aims were to describe the patterns of treatment in a population-based cohort of patients, and compare utilization of RT and chemotherapy to model estimates of need.Methods:Patients diagnosed with Stage III NSCLC between January 1, 2000, to December 31, 2007, were identified from the British Columbia Cancer Agency database. Patients who had prior or concomitant malignancy were excluded. Patient demographics, tumor characteristics, and initial treatment were extracted. Survival data were derived from the British Columbia Vital Statistics Death Listings.Results:2365 patients with Stage III NSCLC were referred, of which 212 patients were excluded, leaving 2153 patients in the study population. Median age was 69 years. Disease stage was IIIA in 49% and IIIB in 51%. Histologies were squamous-cell carcinoma (31%), adenocarcinoma (27%), NSCLC not otherwise specified (31%), and other pathology (11%). Initial treatment included surgery in 12%, RT in 78%, and chemotherapy in 31%. Predicted RT utilization was 77% to 87% and chemotherapy 78%. From 2000 to 2007, curative-intent treatment increased from 21% to 35%, chemoradiotherapy from 8% to 18.6%, and concurrent chemoradiotherapy from 5.1% to 17.6%. Median survival was 30 months for patients who had curative surgery, 21 months for curative RT, 8 months for palliative treatment, and 5 months for best supportive care (p < 0.001).Conclusion:RT utilization was similar to that predicted by models whereas chemotherapy utilization was less. During the study period, the proportion of patients receiving curative chemoradiotherapy doubled and of those receiving concurrent chemoradiotherapy trebled

Iskorištavanje hrane, metaboliti u krvi i ponašanje pri unosu hrane u teladi sahival pasmina odabrane s obzirom na visoki ili niski ostatni unos hrane

This study aimed to evaluate differences in feed utilization between low and high residual feed intake (RFI) in Sahiwal calves by comparing performance, ingestive behavior and blood metabolites. Eighteen, growing, female Sahiwal calves (aged 10-14 months; body weight (BW) 100-125 kg) were fed ad libitum on a total mixed ration for 90 d. RFI varied from -0.53 to 0.40 kg dry matter (DM)/d with a mean RFI of -0.27 to 0.17 kg DM/d in low and high RFI Sahiwal calves, respectively. Calves with low RFI consumed 26% less DM and required 35% less metabolizable energy for body maintenance (MEm) compared to high RFI, yet gained at a similar rate. Low RFI calves digest feed more efficiently than less efficient calves. Conventional efficiency measures also showed better efficiency in low RFI than high RFI calves. Low RFI calves spent less time in feeding, rumination, and chewing. Higher plasma concentrations of insulin-like growth factor-1 (IGF-1), growth hormone (GH), and creatinine, and lower concentrations of albumin, plasma urea nitrogen (PUN), and triglycerides were observed in the low RFI group than the high RFI group. However, plasma total protein, glucose, cholesterol, non esterified fatty acid (NEFA), beta-hydroxy butyric acid (BHBA), calcium (Ca), and phosphorus (P) concentrations were similar in both groups. In summary, low RFI calves utilized feed more efficiently by spending less time and energy in feeding, and the variability in blood metabolites might be due to differences in body metabolism.Ovo istraživanje imalo je za cilj, na temelju proizvodnje, ponašanja kod unosa hrane i metabolita u krvi, procijeniti razlike u iskorištavanju hrane između sahival teladi s niskim ostatnim unosom hrane i visokim ostatnim unosom hrane (Residual Feed Intake - RFI). Osamnaest sahival teladi ženskog spola (u dobi od 10 do -14 mjeseci i tjelesnoj masi od 100 do 125 kg) hranjeno je 90 dana, ad libitum, kompletnim mješovitim obrokom. Ostatni unos hrane kretao se od -0,53 do 0,40 kg suhe tvari/d, sa srednjom vrijednošću od -0,27 kod sahival teladi s niskim ostatnim unosom i srednjom vrijednošću od 0,17 kg kod sahival teladi visokim ostatnim unosom hrane. Iako je telad s niskim ostatnim unosom hrane u odnosu na onu s visokim ostatnim unosom hrane konzumirala 26% manje suhe tvari i zahtijevala 35 % manje uzdržne energije za metabolizam tijela, prirast obje skupne teladi kretao se po sličnoj stopi. Telad s niskim ostatnim unosom hrane imala je učinkovitiju hranidbu što su pokazali i standarni pokazatelji prema kojima je ta telad provela hranidbu u kraćem vremenu, uz kraće žvakanje i preživanje. U usporedbi s teladi koja ima viši ostatni unos hrane, telad s niskim ostatnim unosom hrane imala je u plazmi veće koncentracije inzulinu-sličnog faktora rasta-1 (IGF-1), hormona rasta (GH) i kreatinina, te niže koncentracije albumina, dušika iz ureje i triglicerida. Koncentracije ukupnih proteina, glukoze, kolesterola, neesterificirane masne kiseline (NEFA), betahidroksi maslačne kiseline (BHBA), kalcija (Ca) i fosfora (P) bile su slične u obje skupine teladi. Sažeto, telad s niskim ostatnim unosom hrane iskorištavala je hranu učinkovitije, provodeći kraće vrijeme i trošeći manje energije prilikom hranjenja, a varijacije metabolita u krvi mogle bi biti posljedica razlika u metabolizmu

Feasibility of free breathing Lung MRI for Radiotherapy using non-Cartesian k-space acquisition schemes

Objective: To test a free-breathing MRI protocol for anatomical and functional assessment during lung cancer radiotherapy by assessing two non-Cartesian acquisition schemes based on T1 weighted 3D gradient recall echo sequence: (i) stack-of stars (StarVIBE) and (ii) spiral (SpiralVIBE) trajectories. Methods: MR images on five healthy volunteers were acquired on a wide bore 3T scanner (MAGNETOM Skyra, Siemens Healthcare, Erlangen, Germany). Anatomical image quality was assessed on: (1) free breathing (StarVIBE), (2) the standard clinical sequence (volumetric interpolated breath-hold examination, VIBE) acquired in a 20 second (s) compliant breath-hold and (3) 20 s non-compliant breath-hold. For functional assessment, StarVIBE and the current standard breath-hold time-resolved angiography with stochastic trajectories (TWIST) sequence were run as multiphase acquisitions to replicate dynamic contrast enhancement (DCE) in one healthy volunteer. The potential application of the SpiralVIBE sequence for lung parenchymal imaging was assessed on one healthy volunteer. Ten patients with lung cancer were subsequently imaged with the StarVIBE and SpiralVIBE sequences for anatomical and structural assessment. For functional assessment, free-breathing StarVIBE DCE protocol was compared with breath-hold TWIST sequences on four prior lung cancer patients with similar tumour locations. Image quality was evaluated independently and blinded to sequence information by an experienced thoracic radiologist. Results: For anatomical assessment, the compliant breath-hold VIBE sequence was better than free-breathing StarVIBE. However, in the presence of a non-compliant breath-hold, StarVIBE was superior. For functional assessment, StarVIBE outperformed the standard sequence and was shown to provide robust DCE data in the presence of motion. The ultrashort echo of the SpiralVIBE sequence enabled visualisation of lung parenchyma. Conclusion: The two non-Cartesian acquisition sequences, StarVIBE and SpiralVIBE, provide a free-breathing imaging protocol of the lung with sufficient image quality to permit anatomical, structural and functional assessment during radiotherapy. Advances in knowledge: Novel application of non-Cartesian MRI sequences for lung cancer imaging for radiotherapy. Illustration of SpiralVIBE UTE sequence as a promising sequence for lung structural imaging during lung radiotherapy

A review of segmentation and deformable registration methods applied to adaptive cervical cancer radiation therapy treatment planning

Objective: Manual contouring and registration for radiotherapy treatment planning and online adaptation for cervical cancer radiation therapy in computed tomography (CT) and magnetic resonance images (MRI) are often necessary. However manual intervention is time consuming and may suffer from inter or intra-rater variability. In recent years a number of computer-guided automatic or semi-automatic segmentation and registration methods have been proposed. Segmentation and registration in CT and MRI for this purpose is a challenging task due to soft tissue deformation, inter-patient shape and appearance variation and anatomical changes over the course of treatment. The objective of this work is to provide a state-of-the-art review of computer-aided methods developed for adaptive treatment planning and radiation therapy planning for cervical cancer radiation therapy. Methods: Segmentation and registration methods published with the goal of cervical cancer treatment planning and adaptation have been identified from the literature (PubMed and Google Scholar). A comprehensive description of each method is provided. Similarities and differences of these methods are highlighted and the strengths and weaknesses of these methods are discussed. A discussion about choice of an appropriate method for a given modality is provided. Results: In the reviewed papers a Dice similarity coefficient of around 0.85 along with mean absolute surface distance of 2-4. mm for the clinically treated volume were reported for transfer of contours from planning day to the treatment day. Conclusions: Most segmentation and non-rigid registration methods have been primarily designed for adaptive re-planning for the transfer of contours from planning day to the treatment day. The use of shape priors significantly improved segmentation and registration accuracy compared to other models

Cholesterol-Lowering Probiotics as Potential Biotherapeutics for Metabolic Diseases

Cardiovascular diseases are one of the major causes of deaths in adults in the western world. Elevated levels of certain blood lipids have been reported to be the principal cause of cardiovascular disease and other disabilities in developed countries. Several animal and clinical trials have shown a positive association between cholesterol levels and the risks of coronary heart disease. Current dietary strategies for the prevention of cardiovascular disease advocate adherence to low-fat/low-saturated-fat diets. Although there is no doubt that, in experimental conditions, low-fat diets offer an effective means of reducing blood cholesterol concentrations on a population basis, these appear to be less effective, largely due to poor compliance, attributed to low palatability and acceptability of these diets to the consumers. Due to the low consumer compliance, attempts have been made to identify other dietary components that can reduce blood cholesterol levels. Supplementation of diet with fermented dairy products or lactic acid bacteria containing dairy products has shown the potential to reduce serum cholesterol levels. Various approaches have been used to alleviate this issue, including the use of probiotics, especially Bifidobacterium spp. and Lactobacillus spp.. Probiotics, the living microorganisms that confer health benefits on the host when administered in adequate amounts, have received much attention on their proclaimed health benefits which include improvement in lactose intolerance, increase in natural resistance to infectious disease in gastrointestinal tract, suppression of cancer, antidiabetic, reduction in serum cholesterol level, and improved digestion. In addition, there are numerous reports on cholesterol removal ability of probiotics and their hypocholesterolemic effects. Several possible mechanisms for cholesterol removal by probiotics are assimilation of cholesterol by growing cells, binding of cholesterol to cellular surface, incorporation of cholesterol into the cellular membrane, deconjugation of bile via bile salt hydrolase, coprecipitation of cholesterol with deconjugated bile, binding action of bile by fibre, and production of short-chain fatty acids by oligosaccharides. The present paper reviews the mechanisms of action of anti-cholesterolemic potential of probiotic microorganisms and probiotic food products, with the aim of lowering the risks of cardiovascular and coronary heart diseases

Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its down-regulation by curcumin is independent

<p>Abstract</p> <p>Background</p> <p>Lung cancer is the most lethal cancer and almost 90% of lung cancer is due to cigarette smoking. Even though nicotine, one of the major ingredients of cigarette smoke and the causative agent for addiction, is not a carcinogen by itself, several investigators have shown that nicotine can induce cell proliferation and angiogenesis. We observed that the proliferative index of nicotine is different in the lung cancer cell lines H1299 (p53-/-) and A549 (p53+/+) which indicates that the mode of up-regulation of survival signals by nicotine might be different in cells with and without p53.</p> <p>Results</p> <p>While low concentrations of nicotine induced activation of NF-κB, Akt, Bcl2, MAPKs, AP1 and IAPs in H1299, it failed to induce NF-κB in A549, and compared to H1299, almost 100 times higher concentration of nicotine was required to induce all other survival signals in A549. Transfection of WT-p53 and DN-p53 in H1299 and A549 respectively, reversed the mode of activation of survival signals. Curcumin down-regulated all the survival signals induced by nicotine in both the cells, irrespective of their p53 status. The hypothesis was confirmed when lower concentrations of nicotine induced NF-κB in two more lung cancer cells, Hop-92 and NCI-H522 with mutant p53 status. Silencing of p53 in A549 using siRNA made the cells susceptible to nicotine-induced NF-κB nuclear translocation as in A549 DN-p53 cells.</p> <p>Conclusions</p> <p>The present study reveals a detrimental role of nicotine especially in lung cancer patients with impaired p53 status and identifies curcumin as a potential chemopreventive.</p