We performed a survey using the modified EORTC Facility questionnaire (pFQ) to evaluate the human, technical and organizational resources of particle centers in Europe.
http://ift.tt/2eXtobo
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 29 Ιουλίου 2017
Profile of European proton and carbon ion therapy centers assessed by the EORTC facility questionnaire
Partial breast irradiation with interstitial multi-catheter high-dose-rate brachytherapy. Long-term results of a phase II prospective study
We report the long-term results of phase II prospective study with accelerated partial breast irradiation (APBI) using interstitial multi-catheter high-dose-rate brachytherapy.
http://ift.tt/2hc1wku
Improving the prediction of overall survival for head and neck cancer patients using image biomarkers in combination with clinical parameters
To develop and validate prediction models of overall survival (OS) for head and neck cancer (HNC) patients based on image biomarkers (IBMs) of the primary tumor and positive lymph nodes (Ln) in combination with clinical parameters.
http://ift.tt/2eXtkZc
Angiogenesis Inhibition in the Second-Line Treatment of Metastatic Colorectal Cancer. A Definite Conclusion?
Publication date: Available online 29 July 2017
Source:Seminars in Oncology
Author(s): M. Ducreux, P. Österlund, J.P. Pignon
http://ift.tt/2vh15eW
Stab injury to the preauricular region with laceration of the external carotid artery without involvement of the facial nerve: a case report
Open injuries to the face involving the external carotid artery are uncommon. These injuries are normally associated with laceration of the facial nerve because this nerve is more superficial than the external...
http://ift.tt/2tM6EgZ
Reirradiation for Recurrent Pediatric CNS Malignancies: A Multi-Institutional Review
Publication date: Available online 29 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Avani D. Rao, Arif Rashid, Qinyu Chen, Rosangela C. Villar, Daria Kobyzeva, Kristina Nilsson, Karin Dieckmann, Alexey Nechesnyuk, Ralph Ermoian, Sara Alcorn, Shannon M. MacDonald, Matthew M. Ladra, Eric C. Ford, Brian A. Winey, Maria Luisa S. Figueiredo, Michael J. Chen, Stephanie A. Terezakis
PurposeReirradiation has been proposed as an effective modality for recurrent CNS malignancies for adults. We evaluated toxicity and outcomes of CNS reirradiation in pediatric patients.Methods and MaterialsPediatric patients age <21 years at time of initial diagnosis who developed a recurrent CNS malignancy treated with repeat radiation therapy (RT) across 5 facilities in an international pediatric research consortium were retrospectively reviewed.ResultsSixty-seven pediatric patients were treated with CNS reirradiation. Primary diagnoses included medulloblastoma/primitive neuroendocrine tumor (n=20, 30%), ependymoma (n=19, 28%), germ cell tumor (n=8, 12%), high grade glioma (n=9, 13%), low grade glioma (n=5, 7%), and other (n=6, 9%). Median age at first course of RT was 8.5 years (range:0.5-19.5 years) and 12.3 years (range:3.3-30.2 years) at time of reirradiation. The median time interval between RT courses was 2.0 years (range: 0.3-16.5). Median dose and fractionation of RT in equivalent 2 Gy fractions (EQD2) was 63.7 Gy (range 27.6-74.8 Gy) for initial RT and 53.1 Gy (range 18.6-70.1 Gy) for repeat RT. Location of relapse was infield in 52 patients (78%) and surrounding initial RT field in 15 patients (22%). Thirty-seven patients (58%) underwent gross- or sub-total resection at time of recurrence. Techniques for reirradiation were IMRT (n=46), 3D-CRT (n=9), SRS (n=4, 12-13Gyx1 or 5 Gyx5), protons (n=4), combined modality (n=3), 2D-RT (n=1), and brachytherapy (n=1). Radiation necrosis was detected in 2 cases after first course of RT and 1 additional patient after reirradiation. Six patients (9%) experienced secondary neoplasms following initial RT (1 hematologic, 5 intracranial neoplasms). One patient developed a secondary neoplasm identified shortly after repeat RT. Median overall survival following end of reirradiation was 12.8 months in the entire cohort and 20.5 and 8.4 months for patients with recurrent ependymoma and medulloblastoma following reirradiation.ConclusionsCNS reirradiation in pediatric patients may be a reasonable treatment option with moderate survival noted following repeat RT; although, prospective data characterizing rates of local control and toxicity are needed.
Teaser
This is a unique study evaluating the treatment parameters, toxicity, and outcomes of pediatric CNS reirradiation through a multi-national, multi-institutional pediatric research consortium. Low rates of radiation necrosis were observed and patients experienced reasonable survival rates following repeat radiation therapy to recurrent CNS tumors that may justify the risks of reirradiation.http://ift.tt/2tMwDoF
The potential of proton therapy to reduce acute haematological toxicity in concurrent chemoradiotherapy for oesophageal cancer
Publication date: Available online 29 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Samantha Warren, Christopher N. Hurt, Thomas Crosby, Mike Partridge, Maria A. Hawkins
Radiotherapy dose escalation using a simultaneous integrated boost (SIB) is predicted to improve local tumour control in oesophageal cancer, yet any increase in acute haematological toxicity (HT) could limit the predicted improvement in patient outcome. Proton therapy has been shown to significantly reduce HT in lung cancer patients receiving concurrent chemotherapy, we therefore investigated the potential of bone marrow sparing with protons for oesophageal tumours.21 mid-oesophageal cancer patients treated with conformal radiotherapy (3D50) were selected. Two surrogates for bone marrow were created by outlining thoracic bones (bone) and only the body of the thoracic vertebrae (TV) in Eclipse (Varian). The % overlap of TV with the PTV was recorded for each patient. Additional plans were created retrospectively: a volumetric modulated arctherapy plan (VMAT50) with the same dose as 3D50; a VMAT SIB plan with a dose prescription of 62.5 Gy to the high risk sub-region within the planning treatment volume (VMAT62.5); a re-optimised TV sparing VMAT plan (VMAT62.5bm) and a proton therapy plan (SFO62.5) with the same SIB dose prescription. Bone and TV dose-metrics were recorded and compared across all plans and variation with respect to PTV size and % overlap for each patient was studied.3D50 plans show the highest bone mean dose and TV V30Gy values for each patient. VMAT plans irradiate a larger bone V10Gy volume than 3D50 plans. Re-optimised VMAT62.5bm plans showed improved sparing of the TV volume, but only proton plans showed significant sparing for bone V10Gy and bone mean dose, especially for patients with larger PTV size.
Teaser
Radiotherapy dose escalation is predicted to improve local tumour control in oesophageal cancer, yet any increase in acute haematological toxicity (HT) could limit the predicted improvement in patient outcome. We investigated the bone marrow dose of VMAT, proton plans, and marrow-sparing VMAT plans for oesophageal tumours. Improved marrow sparing was possible with VMAT, but only protons showed significant sparing for bone V10Gy and bone mean dose, especially for patients with larger PTV size.http://ift.tt/2v9mNkg
High- and low-Molecular Weight oat Beta-Glucan Reveals Antitumor Activity in Human Epithelial Lung Cancer
Abstract
Beta-glucans are widely used in treatment, cosmetics, and the food industry. Glucans play a significant role in activation of the immune and antioxidant system and inhibiting tumor proliferation. In the current study the antitumor activities of new high and low molecular weight beta-glucan derived from oats were investigated in two human lung cancer cell line (A549, H69AR) and normal keratinocytes (HaCaT). The effect of high and low molecular weight beta-glucan from oat was evaluated by cellular viability assessment, lipid peroxidation and manganese superoxide dismutase evaluation and cytoskeleton visualisation. Additionally the level of red blood cells hemolysis was performed. Our results indicate strong anti-tumor properties of new beta-glucan from oat and at the same time no toxicity for normal cells.
http://ift.tt/2tMttRL
High- and low-Molecular Weight oat Beta-Glucan Reveals Antitumor Activity in Human Epithelial Lung Cancer
Abstract
Beta-glucans are widely used in treatment, cosmetics, and the food industry. Glucans play a significant role in activation of the immune and antioxidant system and inhibiting tumor proliferation. In the current study the antitumor activities of new high and low molecular weight beta-glucan derived from oats were investigated in two human lung cancer cell line (A549, H69AR) and normal keratinocytes (HaCaT). The effect of high and low molecular weight beta-glucan from oat was evaluated by cellular viability assessment, lipid peroxidation and manganese superoxide dismutase evaluation and cytoskeleton visualisation. Additionally the level of red blood cells hemolysis was performed. Our results indicate strong anti-tumor properties of new beta-glucan from oat and at the same time no toxicity for normal cells.
http://ift.tt/2tMttRL
Primary Mucin Secreting Adenocarcinoma Bladder: a Case Series
Abstract
Primary mucinous adenocarcinoma is an extremely rare type of bladder cancer. These tumours may have varied presenting complains with isolated mucusuria in some patients. As it is difficult to differentiate primary from secondary tumours, it is often a diagnostic dilemma. We narrate three cases of primary mucinous adenocarcinoma bladder and try to bring out the clinical and pathological features unique to this tumour along with the diagnostic importance of immunohistochemistry.
http://ift.tt/2tMmHva
Phase II study of paclitaxel associated with lipid core nanoparticles (LDE) as third-line treatment of patients with epithelial ovarian carcinoma
Abstract
Ovarian cancer is often diagnosed at advanced stages, when poorly responsive to standard treatment. First-line treatment consists in schemes including cytoreductive surgery followed by adjuvant chemotherapy schemes with platinum and taxane derivatives. Second-line regimens are based on gemcitabine and liposomal doxorubicin. Third line is often not worthwhile because of the high toxicity with poor response to treatment. Previously, we showed that paclitaxel (PTX) carried in non-protein lipid core nanoparticles (LDE) resembling the chemical structure of LDL has remarkably reduced toxicity. Here, the hypothesis was tested whether PTX-LDE could safely benefit patients in third-line treatment setting. Fourteen women unresponsive to second-line chemotherapy for ovarian cancer, aged 61 ± 10 years, clinical stage IV and TqNqM1, were included. PTX-LDE was administered at 175 mg/m2, 3/3 week dose. Patients were submitted to clinical examinations before each chemotherapy cycle. Serum biochemistry and imaging examinations to monitor disease progression were performed. In total, 74 cycles of chemotherapy were done and, in all cycles, clinical or laboratorial toxicities were not observed. Median progression-free survival (PFS) was 3.0 months (95% CI 2.0–3.9). In four patients, PFS was >6 months and in 2 > 1 year. The unpreceded, striking absence of toxicity and consistently long PFS, compared to previous results, indicate that at least 4 among 14 patients had tumor arrest by the treatment and clear benefit of PTX-LDE at third-line setting. The absence of observable toxicity allows dose escalating to improve response to treatment, as perspective to be tested in the ensuing studies.
http://ift.tt/2vgLxYt
Intricatinol synergistically enhances the anticancerous activity of cisplatin in human A549 cells via p38 MAPK/p53 signalling
Abstract
Platinum containing drugs are widely used to treat advanced lung carcinomas. However, their clinical success is still limited due to severe side effects, and drug resistance. Alternative approaches are warranted to augment efficacy of platinum based chemotherapeutic drugs with minimal side effects. Intricatinol (INT), a homoisoflavonoid, has been shown to possess anti-tubercular, antioxidant, hypoglycaemic, and hypolipidemic activity. However, its anticancer activity largely remains unknown. In the present study, we have evaluated anticancer potential of INT alone or in combination with cisplatin (CIS) in non-small cell lung carcinoma (A549) cells. Treatment with INT alone reduced the viability of A549 cells in a dose-dependent manner. Interestingly, the combination of low doses of INT and CIS exerted a synergistic effect and induced apoptosis as evident by DNA fragmentation and Annexin V positive cells. Enhanced Bax:Bcl-2 ratio, loss of Δψm, cytochrome c release, cleavage of caspase 3 and PARP1 strongly corroborated our findings. Further, increased expression of p53, p38 MAPK and their phosphorylated counterparts, loss of clonogenicity and reduced migration potential were also recorded with INT + CIS treatment. Most interestingly, INT could not induce any significant cell death in primary mouse embryonic fibroblasts (MEFs). Moreover, no additive or synergistic effect was noted with INT + CIS in MEFs under similar treatment conditions. In conclusion, INT has a selective anticancer potential and could synergize cytotoxicity of CIS. Therefore, the combination of INT and CIS may serve as an effective anticancer strategy for the treatment of non-small cell lung carcinoma.
http://ift.tt/2tLY2a7
Serial changes in lymphocyte subsets in patients with newly diagnosed high grade astrocytomas treated with standard radiation and temozolomide
Abstract
The immune system plays a significant role in cancer prevention and outcome. In high grade astrocytomas (HGA), severe lymphopenia is associated with shortened survival due to tumor progression. This study was performed to quantify serial changes in lymphocyte subsets in HGA following standard radiation (RT) and temozolomide (TMZ). Adults (KPS >60, HIV negative) with newly diagnosed HGA scheduled to receive concurrent RT and TMZ and adjuvant TMZ were eligible. Blood was collected before beginning concurrent RT/TMZ and at weeks 6, 10, 18, and 26, and 3 months after completing adjuvant TMZ. Lymphocyte subsets were analyzed by flow cytometry. Twenty patients (70% glioblastoma, median age 53, 50% male, 80% Caucasian) who enrolled from January 2014 to August 2014 were followed until April 2016. Baseline dexamethasone dose was 0.5 mg/day and 15% had absolute lymphocyte counts (ALC) <1000 cells/mm3 before starting RT/TMZ. However, 75% developed lymphopenia with ALC <1000 cells/mm3 after completion of RT/TMZ. NK cells, B cells and all T lymphocytes subsets dropped significantly after concurrent RT/TMZ and remained depressed for the 48 weeks of observation. The CD4+/CD8+ ratio was not affected significantly during follow-up. Severe lymphopenia involving all subsets occurred early in treatment and remained present for nearly 1 year. To our knowledge, this is the first report of serial trends in lymphocyte subsets following standard RT and TMZ for HGA.
http://ift.tt/2tM7PNt
Comparison of Fatigue, Depression, and Anxiety as Factors Affecting Posttreatment Health-Related Quality of Life in Lung Cancer Survivors
ABSTRACT
Objective
To compare the effects of fatigue, anxiety, and depression on health-related quality of life (HRQoL) in survivors of surgically resectable lung cancer
Methods
In total, 830 lung cancer survivors participated in the study. They completed a questionnaire consisting of items pertaining to sociodemographic characteristics, clinical variables, and HRQoL. We calculated prevalence rates for fatigue, anxiety, and depression and performed multiple logistic regression and general linear modeling to determine the main factors affecting HRQoL.
Results
The prevalence rates for moderate fatigue (Brief Fatigue Inventory mean score: ≥4), borderline depression (Hospital Anxiety and Depression Scale-Depression score: ≥8), and borderline anxiety (Hospital Anxiety and Depression Scale-Anxiety score: ≥8) were 42.2%, 38.9%, and 20.9%, respectively. The main factor was fatigue, which demonstrated the strongest explanatory power for HRQoL including all five functional HRQoL components (i.e., physical, role, emotional, cognitive, and social functioning) and global health status (partial R2 range: .13 to .19). However, anxiety (partial R2 = .21) and fatigue (partial R2 = .19) both demonstrated strong explanatory power for emotional HRQoL. In addition, depression demonstrated weak explanatory power for HRQoL including emotional HRQoL.
Conclusions
Relative to depression and anxiety, fatigue exerted a stronger effect on lung cancer survivors' HRQoL. Health professionals should consider the reduction of fatigue a priority in improving cancer patients' HRQoL following the completion of cancer treatment.
http://ift.tt/2u7cYz5
The impact of hospital volume on perioperative outcomes of rectal cancer
Publication date: Available online 29 July 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Frederik HW. Jonker, Jan Hagemans, Cornelis Verhoef, Pim Burger
BackgroundThe purpose of this study was to investigate the impact of hospital volume on perioperative outcomes of clinical tumour stage (cT)1-3 and cT4 rectal cancer.Methods16.162 patients operated for rectal cancer enrolled in the Dutch Surgical Colorectal Audit between 2009 and 2015 were included. Hospitals were divided into low (<20 cases/year), medium (21-50 cases/year) and high (>50 cases/year) volume for cT1-3 rectal cancer, and for cT4 rectal cancer into low (1-4 cases/year), medium (5-9 cases/year) and high (≥10 cases/year) volume. The influence of hospital volume on perioperative outcomes was investigated.ResultsWith regards to cT1-3 tumours, low volume hospitals were associated with lower risk of complications (33.8% vs. 36.6% and 38.1%, p=0.009), anastomotic leakage (5.4% vs. 8.1% and 8.6%), and reinterventions (11.5% vs. 12.6% and 14.8%, p=0.002) as compared to medium and high volume hospitals. Thirty-day mortality and R0 rates were comparable between groups.In high cT4 volume hospitals, rates of extensive resection of cT4 tumour involvement (49.4% vs. 25.4% and 15.5%, p<0.001) and additional resection of metastasis (17.5% vs. 14.4% and 3.0%, p<0.001) were increased as compared to medium and low volume hospitals. Thirty-day mortality and R0 rates were comparable between groups. In a sub-analysis of pathologic tumour stage 4 patients, irradical resections were increased in low volume hospitals (33.8% vs. 22.5% and 20.8% in medium and high volume hospitals, p=0.031).ConclusionsFor true cT4 rectal cancer, high volume hospitals may offer a better multimodality treatment, while for cT1-3 rectal cancer there appears no benefit for centralization.
http://ift.tt/2vgeqEt
A Prediction Tool Incorporating the Biomarker S-100B for Patient Selection for Completion Lymph Node Dissection in Stage III Melanoma
Publication date: Available online 29 July 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Samantha Damude, Kevin P. Wevers, Raj Murali, Schelto Kruijff, Harald J. Hoekstra, Esther Bastiaannet
IntroductionCompletion lymph node dissection (CLND) in sentinel node (SN)-positive melanoma patients is accompanied with morbidity, while about 80% yield no additional metastases in non-sentinel nodes (NSNs). A prediction tool for NSN involvement could be of assistance in patient selection for CLND. This study investigated which parameters predict NSN-positivity, and whether the biomarker S-100B improves the accuracy of a prediction model.MethodsRecorded clinicopathologic factors were tested for their association with NSN-positivity in 110 SN-positive patients who underwent CLND. A prediction model was developed with multivariable logistic regression, incorporating all predictive factors. Five models were compared for their predictive power by calculating the Area Under the Curve (AUC). A weighted risk score, 'S-100B Non-Sentinel Node Risk Score' (SN-SNORS), was derived for the model with the highest AUC. Besides, a nomogram was developed as visual representation.ResultsNSN-positivity was present in 24 (21.8%) patients. Sex, ulceration, number of harvested SNs, number of positive SNs, and S-100B value were independently associated with NSN-positivity. The AUC for the model including all these factors was 0.78 (95%CI 0.69-0.88). SN-SNORS was the sum of scores for the five parameters. Scores of ≤ 9.5, 10-11.5, and ≥ 12 were associated with low (0%), intermediate (21.0%) and high (43.2%) risk of NSN involvement.ConclusionsA prediction tool based on five parameters, including the biomarker S-100B, showed accurate risk stratification for NSN-involvement in SN-positive melanoma patients. If validated in future studies, this tool could help to identify patients with low risk for NSN-involvement.
http://ift.tt/2tS7uNm
Weekday of gastrectomy for cancer in relation to mortality and oncological outcomes – a Dutch population-based cohort study
Publication date: Available online 29 July 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): E. Visser, H.J.F. Brenkman, R.H.A. Verhoeven, J.P. Ruurda, R.van Hillegersberg
BackgroundSome studies demonstrate that high-complex surgeries performed later in the week are associated with higher postoperative mortality and worse long-term survival. The aim of this cohort study was to determine whether weekday influences outcomes in patients undergoing gastrectomy for cancer.MethodsAll patients who underwent a curative gastrectomy for cancer (2006-2014) were selected from the nationwide population-based Netherlands Cancer Registry. Weekday was analyzed as categorized (Monday-Tuesday versus Wednesday-Friday) and discrete variable (Monday-Friday). The influence of weekday on postoperative 30- and 90-day mortality, and oncological outcomes (lymph node yield, radicality rate and overall survival) was assessed with multivariable logistic and Cox regression analyses.ResultsA total of 3.776 patients were included with a median overall survival of 26.7 months [range 0-120]. The 30- and 90- day mortality were 5% and 8% respectively, median lymph node yield was 13 [range 0-87], and radicality rate was 87%. In multivariable analysis, no influence of weekday was found on postoperative mortality (p>0.05), on R0 resection rates (p>0.05), nor on overall survival (Monday-Friday, HR 1.03, 95%CI 1.01-1.04, p=0.111; Wednesday-Friday vs. Monday-Tuesday, HR 1.05, 95%CI 0.96-1.14, p=0.307). The lymph node yield was significantly lower later in the week compared to earlier (Monday-Friday, OR 0.94, 95%CI 0.89-0.99, p=0.013; Wednesday-Friday vs. Monday-Tuesday OR 0.83, 95%CI 0.71-0.96, p=0.010), which was most apparent in recent years of surgery.ConclusionGastric cancer surgery can be performed safely throughout the week regarding postoperative mortality, radicality and overall survival. A point of concern is a reduced lymph node yield later in the week.
http://ift.tt/2w8SGqh
Failure-to-Rescue in patients undergoing surgery for esophageal or gastric cancer
Publication date: Available online 29 July 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Linde A. Busweiler, Daniel Henneman, Johan L. Dikken, Marta Fiocco, Mark I. van Berge Henegouwen, Bas P. Wijnhoven, Richard van Hillegersberg, Camiel Rosman, Michel W. Wouters, Johanna W. van Sandick
BackgroundComplex surgical procedures such as esophagectomy and gastrectomy for cancer are associated with substantial morbidity and mortality. The purpose of this study was to evaluate trends in postoperative morbidity, mortality, and associated failure-to-rescue (FTR), in patients who underwent a potentially curative resection for esophageal or gastric cancer in the Netherlands, and to investigate differences between the two groups.MethodsAll patients with esophageal or gastric cancer who underwent a potentially curative resection, registered in the Dutch Upper GI Cancer Audit (DUCA) between 2011-2014, were included. Primary outcomes were (major) postoperative complications, postoperative mortality and FTR. To investigate groups' effect on the outcomes of interest a mixed model was used.ResultsOverall, 2644 patients with esophageal cancer and 1584 patients with gastric cancer were included in this study. In patients with gastric cancer, postoperative mortality (7.7% in 2011 vs. 3.8% in 2014) and FTR (38% in 2011 and 19% in 2014) decreased significantly over the years. The adjusted risk of developing a major postoperative complication was lower (OR 0.54; 95% CI 0.42-0.70), but the risk of FTR was higher (OR 1.85; 95% CI 1.05-3.27) in patients with gastric cancer compared to patients with esophageal cancer.ConclusionOnce a postoperative complication occurred, patients with gastric cancer were more likely to die compared to patients with esophageal cancer. Underlying mechanisms like patient selection, and differences in structure and organization of care should be investigated. Next to morbidity and mortality, failure-to-rescue should be considered as an important outcome measure after esophagogastric cancer resections.
http://ift.tt/2vguGVG
p53 signaling pathway polymorphisms, cancer risk and tumor phenotype in TP53 R337H mutation carriers
Abstract
Li-Fraumeni and Li-Fraumeni-like syndrome (LFS/LFL) are clinically heterogeneous cancer predisposition syndromes characterized by diagnosis of early-onset and often multiple cancers with variable tumor patterns and incomplete penetrance. To date, the genetic modifiers described in LFS/LFL have been shown to map to either TP53 or its main negative regulator, MDM2. Additionally, all studies were focused on families with different TP53 germline mutations. Hence, in this study we explored the effect of the most studied polymorphisms of p53 pathway genes on clinical manifestations of individuals carrying the founder TP53 mutation R337H (n = 136) and controls (n = 186). Cancer-affected carriers had been diagnosed either with adrenocortical carcinoma (ACC, n = 29) or breast cancer (BC, n = 43). Allelic discrimation using TaqMan assay was used for genotyping MDM2 SNP 309 (rs2279744) as well as MDM4 (rs1563828) and USP7 (rs1529916) polymorphisms. We found significantly higher MDM2 SNP 309 GG genotype and G allele frequencies in the LFS cohort than in controls. Furthermore, median age at first diagnosis was earlier in MDM2 SNP309 GG carriers when compared to other genotypes for both cancers (ACC: age 1 vs. 2 years; BC: age 35 vs. 43 years, respectively), although not statistically different. The allelic and genotypic frequencies for all SNPs did not differ between cancer affected and unaffected carriers, neither between patients with ACC or BC. In conclusion, our results suggest that MDM2 SNP 309 may contribute to the LFL phenotype and also to an earlier age at diagnosis of ACC and BC cancer in carriers of the R337H founder mutation.
http://ift.tt/2vSA2nq
Cancers, Vol. 9, Pages 98: EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang Equilibrium Recapitulated in Cell Spheroids
Cancers, Vol. 9, Pages 98: EMT/MET at the Crossroad of Stemness, Regeneration and Oncogenesis: The Ying-Yang Equilibrium Recapitulated in Cell Spheroids
Cancers doi: 10.3390/cancers9080098
Authors: Elvira Forte Isotta Chimenti Paolo Rosa Francesco Angelini Francesca Pagano Antonella Calogero Alessandro Giacomello Elisa Messina
The epithelial-to-mesenchymal transition (EMT) is an essential trans-differentiation process, which plays a critical role in embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. It is the fundamental mechanism by which epithelial cells lose many of their characteristics while acquiring features typical of mesenchymal cells, such as migratory capacity and invasiveness. Depending on the contest, EMT is complemented and balanced by the reverse process, the mesenchymal-to-epithelial transition (MET). In the saving economy of the living organisms, the same (Ying-Yang) tool is integrated as a physiological strategy in embryonic development, as well as in the course of reparative or disease processes, prominently fibrosis, tumor invasion and metastasis. These mechanisms and their related signaling (e.g., TGF-β and BMPs) have been effectively studied in vitro by tissue-derived cell spheroids models. These three-dimensional (3D) cell culture systems, whose phenotype has been shown to be strongly dependent on TGF-β-regulated EMT/MET processes, present the advantage of recapitulating in vitro the hypoxic in vivo micro-environment of tissue stem cell niches and their formation. These spheroids, therefore, nicely reproduce the finely regulated Ying-Yang equilibrium, which, together with other mechanisms, can be determinant in cell fate decisions in many pathophysiological scenarios, such as differentiation, fibrosis, regeneration, and oncogenesis. In this review, current progress in the knowledge of signaling pathways affecting EMT/MET and stemness regulation will be outlined by comparing data obtained from cellular spheroids systems, as ex vivo niches of stem cells derived from normal and tumoral tissues. The mechanistic correspondence in vivo and the possible pharmacological perspective will be also explored, focusing especially on the TGF-β-related networks, as well as others, such as SNAI1, PTEN, and EGR1. This latter, in particular, for its ability to convey multiple types of stimuli into relevant changes of the cell transcriptional program, can be regarded as a heterogeneous "stress-sensor" for EMT-related inducers (growth factor, hypoxia, mechano-stress), and thus as a therapeutic target.
http://ift.tt/2vg5YoJ
Statistical science: a grammar for research
Abstract
I greatly appreciate the invitation to give this lecture with its century long history. The title is a warning that the lecture is rather discursive and not highly focused and technical. The theme is simple. That statistical thinking provides a unifying set of general ideas and specific methods relevant whenever appreciable natural variation is present. To be most fruitful these ideas should merge seamlessly with subject-matter considerations. By contrast, there is sometimes a temptation to regard formal statistical analysis as a ritual to be added after the serious work has been done, a ritual to satisfy convention, referees, and regulatory agencies. I want implicitly to refute that idea.
http://ift.tt/2uLydZn
Absolute Postoperative B-Type Natriuretic Peptide Concentrations, but Not Their General Trend, Are Associated With 12-Month, All-Cause Mortality After On-Pump Cardiac Surgery.
BACKGROUND: B-type natriuretic peptide (BNP) is a predictor of mortality after on-pump cardiac surgery. However, previous limited and heterogeneous studies have focused on peak concentrations at 3 to 5 days after surgery and may not offer clinicians much help in early decision-making. After confirming the predictive value of first-postoperative-day BNP in a preliminary analysis, we explored the association between isolated second-postoperative-day BNP concentrations, second-day BNP concentrations in conjunction with first-day BNP concentrations, and the change in BNP (ie, [DELTA]BNP) from the first to the second postoperative day and 12-month, all-cause mortality. METHODS: We included consecutive patients undergoing on-pump cardiac surgery in this observational, secondary analysis of prospectively collected data. We analyzed biomarkers on the first and second postoperative day. [DELTA]BNP was defined as BNP on the second postoperative day minus BNP on the first postoperative day. The primary end point was 12-month, all-cause mortality. The secondary end point was a composite of major adverse cardiac events (MACEs) at 12 months and/or all-cause mortality at 12 months. MACE was defined as nonfatal cardiac arrest, myocardial infarction, and congestive heart failure. The association between BNP and outcomes was examined by receiver operating characteristic curves, as well as univariate and multivariable logistic regression, adjusting for the EuroSCORE II, cross-clamp time, and first-postoperative-day troponin T. RESULTS: We included 1199 patients in the preliminary analysis focused on BNP on postoperative day 1. In the analyses examining BNP variables requiring second-postoperative-day BNP measurement (n = 708), we observed 66 (9.3%) deaths, 48 (6.8%) MACE, and 104 (14.7%) deaths and/or MACE. Both first- and second-postoperative-day BNP were significant independent predictors of all-cause, 12-month mortality per 100 ng/L increase (adjusted odds ratio [aOR], 1.040 [95% confidence interval (CI), 1.019-1.065] and 1.064 [95% CI, 1.031-1.105], respectively). When used in conjunction with one another, first-day BNP was not significant (aOR, 1.021 [95% CI, 0.995-1.048]), while second-day BNP remained significant (aOR, 1.046 [95% CI, 1.008-1.091]). The [DELTA]BNP per 100 ng/L increase was not associated with 12-month, all-cause mortality in the univariable (OR, 0.977 [95% CI, 0.951-1.007]) or multivariable analysis (aOR, 0.989 [95% CI, 0.962-1.021]). CONCLUSIONS: Both absolute concentrations of first- and second-postoperative-day BNP are independent predictors of 12-month, all-cause mortality. When modeled together, second-postoperative-day BNP is more predictive of 12-month, all-cause mortality. Although intuitively appealing, the change in BNP from the first to the second postoperative day is a complex variable and should not routinely be used for prognostication. (C) 2017 International Anesthesia Research Society
http://ift.tt/2haW0hT
http://ift.tt/2haW0hT
The WFSA Global Anesthesia Workforce Survey.
BACKGROUND: Safe anesthesia and surgical care are not available when needed for 5 billion of the world's 7 billion people. There are major deficiencies in the specialist surgical workforce in many parts of the world, and specific data on the anesthesia workforce are lacking. METHODS: The World Federation of Societies of Anaesthesiologists conducted a workforce survey during 2015 and 2016. The aim of the survey was to collect detailed information on physician anesthesia provider (PAP) and non-physician anesthesia provider (NPAP) numbers, distribution, and training. Data were categorized according to World Health Organization regional groups and World Bank income groups. RESULTS: We obtained information for 153 of 197 countries, representing 97.5% of the world's population. There were marked differences in the density of PAPs between World Health Organization regions and between World Bank income groups, ranging from 0 to over 20 PAP per 100,000 population. Seventy-seven countries reported a PAP density of
http://ift.tt/2haQmfI
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Comparison Between the Cobra Perilaryngeal Airway and Laryngeal Mask Airways Under General Anesthesia: A Systematic Review and Meta-analysis.
The complication rate and efficacy of the Cobra Perilaryngeal Airway (CobraPLA) and laryngeal mask airways (LMAs(R)) have been evaluated in the published literature, but the conclusions have been inconsistent. The aim of this systematic review and meta-analysis was thus to assess the performance of the CobraPLA and LMAs under general anesthesia. We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials comparing the CobraPLA with LMAs under general anesthesia. The LMAs used for comparison were the classic LMA (CLMA) and the unique LMA (ULMA). The random effect model was used if heterogeneity was observed, otherwise the fixed effect model was used. Seventeen randomized controlled trials were included; number of studies analyzed for each result are different and were up to 10. The current result suggests that no significant difference between the devices in the insertion success rate at the first attempt. The success rate of first insertion of the CobraPLA was not different from the rates for the CLMA and the ULMA (relative risk: 0.95, 95% confidence interval [CI], 0.91-1.00). CobraPLA insertion was not different from CLMA and ULMA insertion. The CobraPLA provided an oropharyngeal leak pressure higher than that provided by the CLMA (weight mean difference: 3.90, 95% CI, [1.59-6.21] cmH2O) and ULMA (weight mean difference: 6.57, 95% CI, [4.30-8.84] cmH2O). We also found a higher likelihood of blood staining in the airway with the CobraPLA than with the CLMA. In our research, the principal finding of our meta-analysis is that the success rate of first insertion of the CobraPLA was not different from the rate for each of the CLMA and the ULMA, which featured a short learning curve implying its ease of insertion. There was also no significant difference in the incidence of the best view (with a score of 4) obtained with the CobraPLA compared with the other 2 devices. The CobraPLA does seem to be superior to the CLMA and ULMA in providing a higher oropharyngeal leak pressure. The data were insufficient to establish differences in airway adverse events between the groups except for blood staining in the devices, although mucosal trauma occurred more frequently with the Cobra PLA device than with the CLMA and the ULMA. (C) 2017 International Anesthesia Research Society
http://ift.tt/2eVjwyW
http://ift.tt/2eVjwyW
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