To compare the efficacy of anaesthetic depth control using Closed Loop Anaesthesia Delivery System (CLADS) and Target Controlled Infusion (TCI) in patients with moderate to severe left ventricular dysfunction (LVSD).
http://ift.tt/2wTQ2cq
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τετάρτη 30 Αυγούστου 2017
Anaesthetic depth control using closed loop anaesthesia delivery system vs. target controlled infusion in patients with moderate to severe left ventricular systolic dysfunction
The Effect of Atorvastatin on Vascular Function and Structure in Young Adult Survivors of Childhood Cancer: A Randomized, Placebo-Controlled Pilot Clinical Trial
Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.
http://ift.tt/2wpoR6b
Interleukin-8 and nuclear factor kappa B are increased and positively correlated in myelodysplastic syndrome
Abstract
The pathogenesis of myelodysplastic syndromes (MDS) is complex and depends on the interaction between aberrant hematopoietic cells and their microenvironment, probably including aberrations in cytokines and their signaling pathways. To evaluate interleukin-8 (IL-8) plasma levels and nuclear factor kappa B (NF-kB) in patients with MDS and to test possible correlation between IL-8 and NF-Kb, a total of 45 individuals were analyzed: 25 consecutive adult de novo MDS patients and 20 sex and age-matched healthy elderly volunteers. IL-8 analysis was performed by ELISA and activity of NF-kB by chemiluminescent assay. MDS patients showed higher level of IL-8 when compared to controls (p = 0.006). Patients aged 75 and above showed even higher levels (p = 0.035). NF-kB activity was significantly elevated in MDS patients when compared to controls (p < 0.0001) and higher in patients older than 75 years (p = 0.047). NF-kB activity was associated with higher serum ferritin (p = 0.042) and higher percentage of blasts (p = 0.028). A significant positive correlation between IL-8 and NF-kB was demonstrated (r = 0.480; p = 0.015). Many pathways involved in pathophysiology of MDS have been recently described, suggesting that an inflammatory process may act as a pathogenic driver. In this study, significantly elevated levels of IL-8 and NF-kB were demonstrated in MDS patients, with positive association of NF-kB with some markers of poor prognosis. A positive correlation between IL-8 and NF-kB suggests they cooperate as part of a complex networking of immune and inflammatory factors involved in MDS.
http://ift.tt/2wSZnBr
Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients
Abstract
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated with tumor recurrence. After adjustment, among HPV-positive OPSCC patients, high TLR 5 and low TLR 7 expression were associated with poor disease-specific survival. Our results indicate that TLR 5 and 7 may have a role in the prognostication of HPV-positive OPSCC, however, further studies are needed to clarify the comprehensive role of these TLRs in OPSCC.
http://ift.tt/2xynBOs
Factors related with colorectal and stomach cancer screening practice among disease-free lung cancer survivors in Korea
Abstract
Background
Lung cancer survivors are more likely to develop colorectal and stomach cancer than the general population. However, little is known about the current status of gastrointestinal cancer screening practices and related factors among lung cancer survivors.
Methods
We enrolled 829 disease-free lung cancer survivors ≥40 years of age, who had been treated at two hospitals from 2001 to 2006. The patients completed a questionnaire that included stomach and colorectal cancer screening after lung cancer treatment, as well as other sociodemographic variables.
Results
Among lung cancer survivors, correlations with stomach and colorectal screening recommendations were 22.7 and 25.8%, respectively. Of these, 40.7% reported receiving physician advice to screen for second primary cancer (SPC). Those who were recommended for further screening for other cancers were more likely to receive stomach cancer screening [adjusted odds ratios (aOR) = 1.63, 95% confidence interval (CI), 1.16–2.30] and colorectal cancer screening [aOR = 1.37, 95% CI, 0.99–1.90]. Less-educated lung cancer survivors were less likely to have stomach and colorectal cancer screenings.
Conclusions
Lack of a physician's advice for SPC screening and lower educational status had negative impact on the gastrointestinal cancer screening rates of lung cancer survivors.
http://ift.tt/2wjbR3E
Spatial and temporal epithelial ovarian cancer cell heterogeneity impacts Maraba virus oncolytic potential
Abstract
Background
Epithelial ovarian cancer exhibits extensive interpatient and intratumoral heterogeneity, which can hinder successful treatment strategies. Herein, we investigated the efficacy of an emerging oncolytic, Maraba virus (MRBV), in an in vitro model of ovarian tumour heterogeneity.
Methods
Four ovarian high-grade serous cancer (HGSC) cell lines were isolated and established from a single patient at four points during disease progression. Limiting-dilution subcloning generated seven additional subclone lines to assess intratumoral heterogeneity. MRBV entry and oncolytic efficacy were assessed among all 11 cell lines. Low-density receptor (LDLR) expression, conditioned media treatments and co-cultures were performed to determine factors impacting MRBV oncolysis.
Results
Temporal and intratumoral heterogeneity identified two subpopulations of cells: one that was highly sensitive to MRBV, and another set which exhibited 1000-fold reduced susceptibility to MRBV-mediated oncolysis. We explored both intracellular and extracellular mechanisms influencing sensitivity to MRBV and identified that LDLR can partially mediate MRBV infection. LDLR expression, however, was not the singular determinant of sensitivity to MRBV among the HGSC cell lines and subclones. We verified that there were no apparent extracellular factors, such as type I interferon responses, contributing to MRBV resistance. However, direct cell-cell contact by co-culture of MRBV-resistant subclones with sensitive cells restored virus infection and oncolytic killing of mixed population.
Conclusions
Our data is the first to demonstrate differential efficacy of an oncolytic virus in the context of both spatial and temporal heterogeneity of HGSC cells and to evaluate whether it will constitute a barrier to effective viral oncolytic therapy.
http://ift.tt/2gr0O2R
LINE-1 hypermethylation in white blood cell DNA is associated with high-grade cervical intraepithelial neoplasia
Abstract
Background
Long Interspersed Nuclear Elements-1 (LINEs-1) methylation from white blood cells (WBCs) DNA has been proposed as biomarker associated with different types of cancer. The aim of the present study was to investigate the degree of WBCs LINE-1 methylation, according to high-risk Human Papilloma Virus (hrHPV) status in a healthy population, and the association with high-grade Cervical Intraepithelial Neoplasia (CIN2+) in hrHPV positive women.
Methods
Women with abnormal cervical cells were enrolled and classified by histological diagnosis and hrHPV infection. A structured questionnaire was used to obtain information on socio-demographic variables and lifestyle factors. LINE-1 methylation level in WBCs was measured by pyrosequencing-based methylation analysis after bisulfite conversion.
Results
Among 252 women diagnosed with normal cervical epithelium, with regard to LINE-1 methylation level no significant difference was observed between hrHPV positive and hrHPV negative women, also adjusting for known risk factors of infection. The association between WBCs LINE-1 methylation and CIN2+ status was analyzed in hrHPV positive women. The median value of LINE-1 methylation levels was higher in cases (CIN2+) than in controls (75.00% versus 73.17%; p = 0.002). For a one-unit increase in LINE-1 methylation level, the odds of being diagnosed with CIN2+ increased by 10%, adjusting for known factors related to LINE-1 methylation (adjOR: 1.10; 95% CI:1.01–1.20; p = 0.032). The Receiver-Operating Characteristic (ROC) curve analysis identified the cut-off value of 73.8% as the best threshold to separate cases from controls (sensitivity: 63.4% and specificity: 61.8%).
Conclusions
LINE-1 methylation status in WBCs DNA may represent a cost-effective and tissue-accessible biomarker for high-grade CIN in hrHPV positive women. However, LINE-1 hypermethylation cannot be considered specific for cervical cancer (CC) and a model based solely on LINE-1 methylation levels has limited performance. Further investigations are necessary to propose and validate a novel methylation biomarker panel, based on LINE-1 methylation and other differentially methylated regions, for the screening of women at risk of CC.
http://ift.tt/2wjiBOO
Comprehensive genomic profiling in routine clinical practice leads to a low rate of benefit from genotype-directed therapy
Abstract
Background
Describe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options.
Methods
Patients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT.
Results
A total of 125 pediatric and adult patients with a histologically confirmed diagnosis of malignancy were included. Among these, 106 samples were from adult patients, and 19 samples were from pediatric patients. The median age was 54 years for adults. The majority had stage IV malignancy (53%) and were pretreated with 2–3 lines of therapy (45%). The median age was 8 years for pediatric patients. The majority had brain tumors (47%) and had received none or 1 line of therapy (58%) when the profiling was requested. A total of 111 (92%) patients had genomic alterations and were candidates for GDT either via on/off-label use or a clinical trial (phase 1 through 3). Fifteen patients (12%) received GDT based on these results including two patients who were referred for genomically matched phase 1 clinical trials. Three patients (2%) derived benefit from their GDT that ranged from 2 to 6 months of stable disease.
Conclusions
CGP revealed potential treatment options in the majority of patients profiled. However, multiple barriers to therapy were identified, and only a small minority of the patients derived benefit from GDT.
http://ift.tt/2gqPweU
A cross-cultural convergent parallel mixed methods study of what makes a cancer-related symptom or functional health problem clinically important
Abstract
Objective
In this study we investigated what makes a symptom or functional impairment clinically important, that is, relevant for a patient to discuss with a health care professional (HCP). This is the first part of an EORTC Quality of Life Group project focusing on the development of thresholds for clinical importance for the EORTC QLQ-C30 questionnaire and its corresponding computer-adaptive version.
Methods
We conducted interviews with cancer patients and HCPs in six European countries. Participants were asked to name aspects of a symptom or problem that make it clinically important, and to provide importance ratings for a predefined set of aspects (e.g. need for help, limitations of daily functioning).
Results
We conducted interviews with 83 cancer patients (mean age: 60.3y; 50.6% men) and 67 HCPs. Participants related clinical importance to limitations of everyday life (patients: 65.1%, HCPs: 77.6%), the emotional impact of a symptom/problem (patients: 53.0%, HCPs 64.2%), and duration/frequency (patients: 51.8%, HCPs: 49.3%). In the patient sample, importance ratings were highest for worries by partner or family, limitations in everyday life and need for help from the medical staff. HCPs rated limitations in everyday life and need for help from the medical staff to be most important.
Conclusions
Limitations in everyday life, need for (medical) help, and emotional impact on the patient or family/partner were found to be relevant aspects of clinical importance. Based on these findings we will define anchor items for the development of thresholds for clinical importance for the EORTC measures in a Europe-wide field study.
http://ift.tt/2wpcYNE
A cross-cultural convergent parallel mixed methods study of what makes a cancer-related symptom or functional health problem clinically important
Abstract
Objective
In this study we investigated what makes a symptom or functional impairment clinically important, that is, relevant for a patient to discuss with a health care professional (HCP). This is the first part of an EORTC Quality of Life Group project focusing on the development of thresholds for clinical importance for the EORTC QLQ-C30 questionnaire and its corresponding computer-adaptive version.
Methods
We conducted interviews with cancer patients and HCPs in six European countries. Participants were asked to name aspects of a symptom or problem that make it clinically important, and to provide importance ratings for a predefined set of aspects (e.g. need for help, limitations of daily functioning).
Results
We conducted interviews with 83 cancer patients (mean age: 60.3y; 50.6% men) and 67 HCPs. Participants related clinical importance to limitations of everyday life (patients: 65.1%, HCPs: 77.6%), the emotional impact of a symptom/problem (patients: 53.0%, HCPs 64.2%), and duration/frequency (patients: 51.8%, HCPs: 49.3%). In the patient sample, importance ratings were highest for worries by partner or family, limitations in everyday life and need for help from the medical staff. HCPs rated limitations in everyday life and need for help from the medical staff to be most important.
Conclusions
Limitations in everyday life, need for (medical) help, and emotional impact on the patient or family/partner were found to be relevant aspects of clinical importance. Based on these findings we will define anchor items for the development of thresholds for clinical importance for the EORTC measures in a Europe-wide field study.
http://ift.tt/2wpcYNE
Inter-observer agreement among pathologists in grading the pathological response to neoadjuvant chemotherapy in breast cancer
Abstract
Background
The degree of pathological response to neoadjuvant chemotherapy (NAC) was correlated with the prognosis in breast cancer. There are few studies published on inter-observer variability in the assessment of pathological responses among pathologists.
Methods
We collected 64 surgically resected specimens from patients who had received NAC. Three pathologists assessed the pathological responses and classified them into 7 grades according to grading system of the Japanese Breast Cancer Society. The levels of concordance among pathologists were categorized into 3 classes: full concordance (all pathologists gave the same grade), partial concordance (two of them gave the same grade), and discordance (all three gave different grades). The inter-observer agreement among pathologists was estimated using the percentage concordance and Cohen's kappa statistics.
Results
Full concordance, partial concordance, and discordance were seen in 28 (43%), 33 (52%), and 3 (5%) specimens, respectively. In most of partial concordance specimens (30 out of 33), the pathological response grades differed by only one level. The kappa value was 0.59. The concordance rate with regard to pCR was 97%.
Conclusions
Most of the judgments among pathologists differed within one level, but there is room for improving harmonization in the assessment of pathological responses.
http://ift.tt/2wiTA6s
Modified Stem Cells Deliver Chemotherapy to Metastatic Tumors
Researchers have used modified stem cells to deliver a cancer drug selectively to metastatic breast cancer tumors in mice. The stem cells target metastatic tumors by homing in on the stiff environment that typically surrounds them.
http://ift.tt/2vKOjRB
Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients
Abstract
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated with tumor recurrence. After adjustment, among HPV-positive OPSCC patients, high TLR 5 and low TLR 7 expression were associated with poor disease-specific survival. Our results indicate that TLR 5 and 7 may have a role in the prognostication of HPV-positive OPSCC, however, further studies are needed to clarify the comprehensive role of these TLRs in OPSCC.
http://ift.tt/2xynBOs
Cancer-related risk factors and incidence of major cancers by race, gender and region; analysis of the NIH-AARP diet and health study
Abstract
Background
Racial disparities in the incidence of major cancers may be attributed to differences in the prevalence of established, modifiable risk factors such as obesity, smoking, physical activity and diet.
Methods
Data from a prospective cohort of 566,398 adults aged 50–71 years, 19,677 African-American and 450,623 Whites, was analyzed. Baseline data on cancer-related risk factors such as smoking, alcohol, physical activity and dietary patterns were used to create an individual adherence score. Differences in adherence by race, gender and geographic region were assessed using descriptive statistics, and Cox proportional hazards models were used to determine the association between adherence and cancer incidence.
Results
Only 1.5% of study participants were adherent to all five cancer-related risk factor guidelines, with marked race-, gender- and regional differences in adherence overall. Compared with participants who were fully adherent to all five cancer risk factor criteria, those adherent to one or less had a 76% increased risk of any cancer incidence (HR: 1.76, 95% CI: 1.70 – 1.82), 38% increased risk of breast cancer (HR: 1.38, 95% CI: 1.25 – 1.52), and doubled the risk of colorectal cancer (HR: 2.06, 95% CI: 1.84 – 2.29). However, risk of prostate cancer was lower among participants adherent to one or less compared with those who were fully adherent (HR: 0.79, 95% CI: 0.75 – 0.85). The proportion of cancer incident cases attributable to low adherence was higher among African-Americans compared with Whites for all cancers (21% vs. 19%), and highest for colorectal cancer (25%) regardless of race.
Conclusion
Racial differences in the proportion of cancer incidence attributable to low adherence suggests unique opportunities for targeted cancer prevention strategies that may help eliminate racial disparities in cancer burden among older US adults.
http://ift.tt/2wiXNY1
Chemoradiotherapy versus surgery followed by postoperative radiotherapy in tonsil cancer: Korean Radiation Oncology Group (KROG) study
Abstract
Background
Treatment of tonsil cancer, a subset of oropahryngeal cancer, varies between surgery and radiotherapy. Well-designed studies in tonsil cancer have been rare and it is still controversial which treatment is optimal. This study aimed to assess the outcome and failure patterns in tonsil cancer patients treated with either approaches.
Methods
We retrospectively reviewed medical records of 586 patients with tonsil cancer, treated between 1998 and 2010 at 16 hospitals in Korea. Two hundred and one patients received radiotherapy and chemotherapy (CRT), while 385 patients received surgery followed by radiotherapy and/or chemotherapy (SRT). Compared with the SRT group, patients receiving CRT were older, with more advanced T stage and received higher radiotherapy dose given by intensity modulation techniques. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and clinicopathologic factors were analyzed.
Results
At follow-up, the 5-year OS, DFS, LRRFS and DMFS rates in the CRT group were 82, 78, 89, and 94%, respectively, and in the SRT group were 81, 73, 87, and 89%, respectively. Old age, current smoking, poor performance status, advanced T stage, nodal involvement, and induction chemotherapy were associated with poor OS. Induction chemotherapy had a negative prognostic impact on OS in both treatment groups (p = 0.001 and p = 0.033 in the CRT and SRT groups, respectively).
Conclusions
In our multicenter, retrospective study of tonsil cancer patients, the combined use of radiotherapy and chemotherapy resulted in comparable oncologic outcome to surgery followed by postoperative radiotherapy, despite higher-risk patients having been treated with the definitive radiotherapy. Induction chemotherapy approaches combined with either surgery or definitive radiotherapy were associated with unfavorable outcomes.
http://ift.tt/2xyBFr6
Self-reported sexual health: Breast cancer survivors compared to women from the general population – an observational study
Abstract
Background
Cancer survivorship is of increasing importance in post-treatment care. Sexual health (SH) and femininity can be crucial issues for women surviving cancer. We aimed to determine a more complete understanding of the contribution that a breast cancer (BC) diagnosis and its treatment exert on patients' follow-up SH. For this purpose, self-reported levels and predictors of SH in breast cancer survivors (BCS) were compared with those of women with no previous or current BC (WNBC).
Methods
BCS and WNBC underwent a comprehensive, cross-sectional patient-reported outcome (PRO) assessment. Validated PRO instruments were used to measure SH, body image, anxiety and depression and menopausal symptoms. Assessments were performed within the routine clinical setting.
Instruments used were the Sexual Interest and Desire Inventory - Female, Sexual Activity Questionnaire, Body Image Scale, Hospital Anxiety and Depression Scale and the Menopause-Specific Quality of Life Questionnaire.
Results
One hundred five BCS (average time since diagnosis of 3 years) and 97 WNBC with a mean age of 49 years completed the assessment. SH was significantly worse in BCS compared to WNBC (p = 0.005; BCS SIDI-F mean = 24.9 vs. WNBC mean = 29.8). 68.8% of BCS and 58.8% of WNBC met criteria of a hypo-active sexual desire disorder. Higher depressive symptoms, higher age and lower partnership satisfaction were predictive for poorer SH in BCS.
Conclusion
SH problems are apparent in BCS and differ significantly from those seen in the general population. Consequently, BC survivorship care should include interventions to ameliorate sexual dysfunction and provide help with depressive symptoms and partnership problems, which are associated with poor BCS SH.
http://ift.tt/2wiXwnN
Innovative dressing and securement of tunneled central venous access devices in pediatrics: a pilot randomized controlled trial
Abstract
Background
Central venous access device (CVAD) associated complications are a preventable source of patient harm, frequently resulting in morbidity and delays to vital treatment. Dressing and securement products are used to prevent infectious and mechanical complications, however current complication rates suggest customary practices are inadequate. The aim of this study was to evaluate the feasibility of launching a full-scale randomized controlled efficacy trial of innovative dressing and securement products for pediatric tunneled CVAD to prevent complication and failure.
Methods
An external, pilot, four-group randomized controlled trial of standard care (bordered polyurethane dressing and suture), in comparison to integrated securement-dressing, suture-less securement device, and tissue adhesive was undertaken across two large, tertiary referral pediatric hospitals in Australia. Forty-eight pediatric participants with newly inserted tunneled CVADs were consecutively recruited. The primary outcome of study feasibility was established by elements of eligibility, recruitment, attrition, protocol adherence, missing data, parent and healthcare staff satisfaction and acceptability, and effect size estimates for CVAD failure (cessation of function prior to completion of treatment) and complication (associated bloodstream infection, thrombosis, breakage, dislodgement or occlusion). Dressing integrity, product costs and site complications were also examined.
Results
Protocol feasibility was established. CVAD failure was: 17% (2/12) integrated securement-dressing; 8% (1/13) suture-less securement device; 0% tissue adhesive (0/12); and, 0% standard care (0/11). CVAD complications were: 15% (2/13) suture-less securement device (CVAD associated bloodstream infection, and occlusion and partial dislodgement); 8% (1/12) integrated securement-dressing (partial dislodgement); 0% tissue adhesive (0/12); and, 0% standard care (0/11). One CVAD-associated bloodstream infection occurred, within the suture-less securement device group. Overall satisfaction was highest in the integrated securement-dressing (mean 8.5/10; standard deviation 1.2). Improved dressing integrity was evident in the intervention arms, with the integrated securement-dressing associated with prolonged time to first dressing change (mean days 3.5).
Conclusions
Improving the security and dressing integrity of tunneled CVADs is likely to improve outcomes for pediatric patients. Further research is necessary to identify novel, effective CVAD securement to reduce complications, and provide reliable vascular access for children.
Trial registration
ACTRN12614000280606; prospectively registered on 17/03/2014.
http://ift.tt/2xy1OGt
CTLA-4/CD80 pathway regulates T cell infiltration into pancreatic cancer
Abstract
The ability of some tumors to exclude effector T cells represents a major challenge to immunotherapy. T cell exclusion is particularly evident in pancreatic ductal adenocarcinoma (PDAC), a disease where blockade of the immune checkpoint molecule CTLA-4 has not produced significant clinical activity. In PDAC, effector T cells are often scarce within tumor tissue and confined to peritumoral lymph nodes and lymphoid aggregates. We hypothesized that CTLA-4 blockade, despite a lack of clinical efficacy seen thus far in PDAC, might still alter T cell immunobiology, which would have therapeutic implications. Using clinically relevant genetic models of PDAC, we found that regulatory T cells (Tregs), which constitutively express CTLA-4, accumulate early during tumor development but are largely confined to peritumoral lymph nodes during disease progression. Tregs were observed to regulate CD4+, but not CD8+, T cell infiltration into tumors through a CTLA-4/CD80 dependent mechanism. Disrupting CTLA-4 interaction with CD80 was sufficient to induce CD4 T cell infiltration into tumors. These data have important implications for T cell immunotherapy in PDAC and demonstrate a novel role for CTLA-4/CD80 interactions in regulating T cell exclusion. In addition, our findings suggest distinct mechanisms govern CD4+ and CD8+ T cell infiltration in PDAC.
http://ift.tt/2iJ1sJA
Up-regulation of lncRNA CASC9 promotes esophageal squamous cell carcinoma growth by negatively regulating PDCD4 expression through EZH2
Abstract
Background
Abnormal expression of numerous long non-coding RNAs (lncRNAs) has been reported in esophageal squamous cell carcinoma (ESCC) recently, but the great majority of their roles and mechanisms remain largely unclear. We aim to identify the critical ESCC-associated lncRNAs and elucidate the functions and mechanisms in detail.
Methods
Microarrays were used to analyze the differentially expressed lncRNAs in ESCC tissues. qRT-PCR was used to verify the result of microarrays. The effects of the most up-regulated lncRNA, cancer susceptibility candidate 9(CASC9), on cell growth, proliferation and cell cycle were investigated by in vivo and in vitro assays. Microarrays and recovery tests were used to discover the regulatory targets of CASC9. RNA FISH and subcellular fractionation assays were used to detect the subcellular location of CASC9. Finally, the mechanism of CASC9 regulating PDCD4 was explored by RIP, RNA-protein pull down and ChIP assays.
Results
ESCC tissue microarrays showed that CASC9 was the most up-regulated lncRNA. qRT-PCR analysis indicated that CASC9 expression was positively associated with tumor size and TNM stage, and predicted poor overall survival of ESCC patients. Knockdown of CASC9 inhibited ESCC cell growth in vitro and tumorigenesis in nude mice. Furthermore interfering CASC9 decreased cell proliferation and blocked cell cycle G1/S transition. CASC9-associated microarrays indicated that PDCD4 might be the target of CASC9. Consistent with this, PDCD4 expression was negatively associated with CASC9 expression in ESCC tissues and predicted good prognosis. Manipulating CASC9 expression in ESCC cells altered both PDCD4 mRNA and protein levels and cell cycle arrest caused by CASC9 knockdown could be rescued by suppressing PDCD4 expression. CASC9 located both in the nucleus and cytoplasm. Mechanistically, enhancer of zeste homolog2 (EZH2) could bind to both CASC9 and PDCD4 promoter region. Interfering CASC9 reduced the enrichment of EZH2 and H3K27me3 in the PDCD4 promoter region.
Conclusions
Our study firstly demonstrates that lncRNA CASC9 functions as an oncogene by negatively regulating PDCD4 expression through recruiting EZH2 and subsequently altering H3K27me3 level. Our study implicates lncRNA CASC9 as a valuable biomarker for ESCC diagnosis and prognosis.
http://ift.tt/2wSVT1t
The biology of Hepatocellular carcinoma: implications for genomic and immune therapies
Abstract
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is a leading cause of cancer-related death worldwide. It is highly refractory to most systemic therapies. Recently, significant progress has been made in uncovering genomic alterations in HCC, including potentially targetable aberrations. The most common molecular anomalies in this malignancy are mutations in the TERT promoter, TP53, CTNNB1, AXIN1, ARID1A, CDKN2A and CCND1 genes. PTEN loss at the protein level is also frequent. Genomic portfolios stratify by risk factors as follows: (i) CTNNB1 with alcoholic cirrhosis; and (ii) TP53 with hepatitis B virus-induced cirrhosis. Activating mutations in CTNNB1 and inactivating mutations in AXIN1 both activate WNT signaling. Alterations in this pathway, as well as in TP53 and the cell cycle machinery, and in the PI3K/Akt/mTor axis (the latter activated in the presence of PTEN loss), as well as aberrant angiogenesis and epigenetic anomalies, appear to be major events in HCC. Many of these abnormalities may be pharmacologically tractable. Immunotherapy with checkpoint inhibitors is also emerging as an important treatment option. Indeed, 82% of patients express PD-L1 (immunohistochemistry) and response rates to anti-PD-1 treatment are about 19%, and include about 5% complete remissions as well as durable benefit in some patients. Biomarker-matched trials are still limited in this disease, and many of the genomic alterations in HCC remain challenging to target. Future studies may require combination regimens that include both immunotherapies and molecularly matched targeted treatments.
http://ift.tt/2xN9Quz
CRCHD Hosts Career Development and Scientific Workshop
CRCHD recently hosted a Career Development and Scientific Workshop to support investigators interested in applying for Continuing Umbrella of Research Experiences (CURE) and cancer health disparities translational research funding opportunities.
http://ift.tt/2wSqQTP
Pulmonary tumor embolism secondary to soft tissue and bone sarcomas: a case report and literature review
Abstract
Background
Tumor embolisms (TE) are an underappreciated source of pulmonary embolisms in sarcoma. Most evidence in the literature is limited to case reports and none have described the presence of TE secondary to myxofibrosarcoma. We report the first case of myxofibrosarcoma TE and perform a review of the literature for TE secondary to bone and soft tissue sarcomas (STS).
Case presentation
A 36-year-old female presented with debilitating pain of the right upper extremity secondary to a recurrent soft tissue sarcoma. She had distant metastasis to the lung. An MRI revealed a 25-cm shoulder mass involving the proximal arm muscles with encasement of the axillary artery, vein, and brachial plexus. A palliative forequarter amputation was performed and tumor thrombus was evident within the axillary artery and vein. Postoperatively, she developed an acute onset of dyspnea and hypoxia. A computed tomography scan revealed a pulmonary saddle embolism. A bilateral lower extremity venous duplex was negative. She became hemodynamically unstable despite resuscitation and was placed on vasopressor support. A transthoracic echocardiogram revealed elevated pulmonary artery pressure, tricuspid regurgitation, right heart dilation, and reduced right heart systolic function consistent with acute cor pulmonale. The patient did not want to pursue a median sternotomy with pulmonary artery embolectomy and expired from cardiopulmonary arrest within 24 h of the operation. The final pathology revealed a 25 × 16 × 13 cm high-grade myxofibrosarcoma with invasion into the bone, skin, and neurovascular bundle as well as evidence of tumor thrombus.
Conclusion
TE is a rare but deadly cause of pulmonary embolism in sarcoma. A high index of suspicion is necessary in individuals who present with respiratory-related symptoms, especially dyspnea. Diagnostic confirmation with a computed tomography scan of the chest and echocardiogram should be rapid. Unlike venous thromboembolism, pulmonary embolectomy remains the preferred therapeutic approach.
http://ift.tt/2wT4mBT
Gefitinib-loaded DSPE-PEG2000 nanomicelles with CD133 aptamers target lung cancer stem cells
Abstract
Background
Lung cancer stem cells (CSCs) are considered to be the seed of lung cancer, and CD133 is a marker of lung CSCs. Here, we developed gefitinib-loaded poly(ethylene glycol) 2000-distearoylphosphatidylethanolamine nanomicelles with CD133 aptamers (M-Gef-CD133) to eliminate CD133+ lung CSCs.
Methods
M-Gef-CD133 was prepared using a lipid-film-based approach. The targeting and activity of M-Gef-CD133 towards lung CSCs were evaluated.
Results
M-Gef-CD133 were small (25 nm) and showed enhanced cytotoxic effect towards CD133+ lung CSCs compared with non-targeted M-Gef and gefitinib. Notably, M-Gef-CD133 could significantly reduce tumor sphere formation and the percentage of CD133+ lung CSCs, indicating that it possesses selective toxicity against CD133+ lung CSCs.
Conclusions
The interaction of CD133 aptamers and CD133 shows promise in the delivery of gefitinib to CD133+ lung CSCs, and M-Gef-CD133 represents a promising treatment to target lung CSCs.
http://ift.tt/2xMW62T
Exosomes isolated from cancer patients’ sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells
Abstract
Background
Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients' sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes. In the present study, we tested the hypothesis that cancer patients' sera-derived exosomes might be responsible for the malignant transformation of target cells and that oncosuppressor mutation would promote their increased uptake. We also sought to unveil the mechanisms behind the hypothesized phenomena.
Methods
We used human BRCA1 knockout (BRCA1-KO) fibroblasts as target cells. Cells were treated in vitro with cancer patients' sera or cancer patients' sera-derived exosomes. Treated cells were injected into NOD-SCID mice. Immunohistochemical analyses were performed to determine the differentiation state of the xenotransplants. Mass spectrometry analyses of proteins from cancer exosomes and the BRCA1-KO fibroblasts' membrane were performed to investigate possible de novo expression of molecules involved in vesicles uptake. Blocking of the identified molecules in vitro was performed and in vivo experiments were conducted to confirm the role of these molecules in the malignant transformation carried out by cancer-derived exosomes.
Results
Cells treated with exosomes isolated from cancer patients' sera underwent malignant transformation and formed tumors when transplanted into immunodeficient mice. Histological analyses showed that the tumors were carcinomas that differentiated into the same lineage of the primary tumors of blood donors. Oncosuppressor mutation promoted the de novo expression, on the plasma membrane of target cells, of receptors, responsible for the increased uptake of cancer-derived exosomes. The selective blocking of these receptors inhibited the horizontal transfer of malignant traits.
Conclusion
These findings strengthen the hypothesis that oncogenic factors transferred via circulating cancer exosomes, induce malignant transformation of target cells even at distance. Oncosuppressor genes might protect the integrity of the cell genome by inhibiting the uptake of cancer-derived exosomes.
http://ift.tt/2vsuuDl
Risk of depression, anxiety, and adjustment disorders in women with a suspected but unconfirmed diagnosis of breast or genital organ cancer in Germany
Abstract
Background
Breast cancer (BC) and genital organ cancers (GOC) are known to have a major impact on the quality of life of patients. The aim of this study was to analyze the risk of depression, anxiety, and adjustment disorders in women in Germany with a suspected but unconfirmed diagnosis of BC or GOC in their medical history.
Methods
This study included women who received a suspected diagnosis of BC or GOC and were followed between 2007 and 2015 (index date). These women were matched (1:1:1) by age to women with a confirmed diagnosis of BC or GOC and women without a cancer diagnosis. The main outcome measure of the study was the rate of depression, anxiety, and adjustment disorder diagnoses within 3 years of the index date.
Results
The present analysis included a total of 4,842 patients (mean age = 49.3 years). Within 3 years of the index date, 23.5% of women with a confirmed diagnosis of BC or GOC, 14.1% of those with a suspected diagnosis of BC or GOC, and 10.5% of those without a cancer diagnosis developed depression, anxiety, or an adjustment disorder (log-rank p value <0.001). Women with a suspected diagnosis of cancer were at a higher risk for these psychiatric conditions than those without a cancer diagnosis (BC and GOC: HR 1.32; BC: HR 1.21; GOC: HR 1.50).
Conclusion
A suspected diagnosis of BC or GOC in a woman's medical history is associated with an increased risk of developing depression, anxiety, and adjustment disorders.
http://ift.tt/2gozQJg
Divergent trends in lung cancer incidence by gender, age and histological type in Estonia: a nationwide population-based study
Abstract
Background
Lung cancer (LC) is the leading cause of cancer deaths in men and the second most frequent cause of cancer deaths in women in Estonia. The study aimed to analyze time trends in LC incidence and mortality in Estonia over the 30-year period, which included major social, economic and health care transition. The results are discussed in the context of changes in tobacco control and smoking prevalence. Long-term predictions of incidence and mortality are provided.
Methods
Data for calculating the incidence and mortality rates in 1985–2014 were obtained from the nationwide population-based Estonian Cancer Registry and the Causes of Death Registry. Joinpoint regression was used to analyze trends and estimate annual percentage change (APC) with 95% confidence interval (CI). Nordpred model was used to project future incidence and mortality trends for 2015–2034.
Results
Incidence peaked among men in 1991 and decreased thereafter (APC: -1.5, 95% CI: -1.8; −1.3). A decline was seen for all age groups, except age ≥ 75 years, and for all histological types, except adenocarcinoma and large cell carcinoma. Incidence among women increased overall (APC: 1.6, 95% CI: 1.1; 2.0) and in all age groups and histological types, except small cell carcinoma. Age-standardized incidence rate (world) per 100,000 was 54.2 in men and 12.9 in women in 2014. Changes in mortality closely followed those in incidence. According to our predictions, the age-standardized incidence and mortality rates will continue to decrease in men and reach a plateau in women.
Conclusions
The study revealed divergent LC trends by gender, age and histological type, which were generally consistent with main international findings. Growing public awareness and stricter tobacco control have stimulated overall favorable changes in men, but not yet in women. Large increase in incidence was observed for adenocarcinoma, which in men showed a trend opposite to the overall decline. LC will remain a serious public health issue in Estonia due to a high number of cases during the next decades, related to aging population, and previous and current smoking patterns. National tobacco control policy in Estonia should prioritize preventing smoking initiation and promoting smoking cessation, particularly among women.
http://ift.tt/2iGuY2E
VEGFR2 regulates endothelial differentiation of colon cancer cells
Abstract
Background
Recent studies suggested that cancer stem-like cells contribute to tumor vasculogenesis by differentiating into endothelial cells. However, such process is governed by still undefined mechanism.
Methods
At varying differentiation levels, three representative colon cancer cells were cultured in endothelial-inducing conditioned medium: human colon cancer cells HCT116 (HCT116) (poorly differentiated), SW480 (moderately differentiated), and HT29 (well differentiated). We tested for expression of endothelial markers (cluster of differentiation (CD) 31, CD34, and vascular endothelial (VE)-cadherin and their ability to form tube-like structures in 3D culture. We also observed VEGF secretion and expressions of endothelial markers and VEGFRs in HCT116 cells under hypoxia to simulate physiological conditions. In in vitro and in xenotransplantation experiments, VE growth factor receptor 2 (VEGFR2) antagonist SKLB1002 was used to test effect of VEGFR2 in endothelial differentiation of HCT116 cells. Expression levels of VEGFR2 and VE-cadherin were assessed by immunohistochemistry of human colon cancer tissues to evaluate clinicopathological significance of VEGFR2.
Results
After culturing in endothelial-inducing conditioned medium, poorly differentiated HCT116 cells expressed endothelial markers and formed tube-like structure in vitro. HCT116 cells secreted more endogenous VEGF and expressed higher VEGFR2 under hypoxia. SKLB1002 impaired endothelial differentiation in vitro and xenotransplantation experiments, suggesting a VEGFR2-dependent mechanism. Increased expression of VEGFR2 correlated with differentiation, metastasis/recurrence, and poor prognosis in 203 human colon cancer samples. Positive correlation was observed between VEGFR2 and VE-cadherin expression.
Conclusions
VEGFR2 regulates endothelial differentiation of colon cancer cell and may be potential platform for anti-angiogenesis cancer therapy.
http://ift.tt/2gqpYif
Novel three-dimensional bone ‘mapping’ software can help assess progression of osseous metastases from routine CT
Abstract
Imaging of bone metastasis response to therapy is a research priority. Stradwin is a new software-tool, with demonstrated sub-voxel accuracy in assessing cortical bone properties from routine CT. We applied this technology to the context of osseous metastases, with particular focus on disease progression using prostate cancer as a model. 3D–rendered 'bone-maps' were produced for 20 men with advanced prostate cancer, including a sub-cohort of 9 who had undergone serial scans. Correlation between baseline interpretation and assessments of progression between modalities was assessed. Bone-maps took significantly less time to interpret than CT bone windows (P < 0.001). Initial bone-mapping, without adjustment, demonstrated sensitivity and specificity for suspicious areas on CT of 70.7% and 73.1% respectively. Evaluating disease over time, concordance between bone-maps and current practice using RECIST outcomes was 100%.
This study demonstrates the feasibility and potential use of this free post-processing software in the serial assessment of osseous metastases.
http://ift.tt/2vsjgPh
CTLA-4/CD80 pathway regulates T cell infiltration into pancreatic cancer
Abstract
The ability of some tumors to exclude effector T cells represents a major challenge to immunotherapy. T cell exclusion is particularly evident in pancreatic ductal adenocarcinoma (PDAC), a disease where blockade of the immune checkpoint molecule CTLA-4 has not produced significant clinical activity. In PDAC, effector T cells are often scarce within tumor tissue and confined to peritumoral lymph nodes and lymphoid aggregates. We hypothesized that CTLA-4 blockade, despite a lack of clinical efficacy seen thus far in PDAC, might still alter T cell immunobiology, which would have therapeutic implications. Using clinically relevant genetic models of PDAC, we found that regulatory T cells (Tregs), which constitutively express CTLA-4, accumulate early during tumor development but are largely confined to peritumoral lymph nodes during disease progression. Tregs were observed to regulate CD4+, but not CD8+, T cell infiltration into tumors through a CTLA-4/CD80 dependent mechanism. Disrupting CTLA-4 interaction with CD80 was sufficient to induce CD4 T cell infiltration into tumors. These data have important implications for T cell immunotherapy in PDAC and demonstrate a novel role for CTLA-4/CD80 interactions in regulating T cell exclusion. In addition, our findings suggest distinct mechanisms govern CD4+ and CD8+ T cell infiltration in PDAC.
http://ift.tt/2iJ1sJA
Side effects of radiotherapy in breast cancer patients
Abstract
Aim
Breast cancer is the most common cancer type among women necessitating adjuvant radiotherapy. As the Internet has become a major source of information for cancer patients, this study aimed to evaluate the quality of websites giving information on side effects of radiotherapy for breast cancer patients.
Methods
A patients' search for the English terms "breast cancer – radiotherapy – side effects" and the corresponding German terms "Brustkrebs – Strahlentherapie – Nebenwirkungen" was carried out twice (5 months apart) using the search engine Google. The first 30 search results each were evaluated using the validated 16-question DISCERN Plus instrument, the Health on the Net Code of Conduct (HONcode) certification and the Journal of the American Medical Association (JAMA) benchmark criteria. The overall quality (DISCERN score) of the retrieved websites was further compared to queries via Bing and Yahoo search engines.
Results
The DISCERN score showed a great range, with the majority of websites ranking fair to poor. Significantly superior results were found for English websites, particularly for webpages run by hospitals/universities and nongovernmental organizations (NGO), when compared to the respective German categories. In general, only a minority of websites met all JAMA benchmarks and was HONcode certified (both languages). We did not determine a relevant temporal change in website ranking among the top ten search hits, while significant variation occurred thereafter. Mean overall DISCERN score was similar between the various search engines.
Conclusion
The Internet can give breast cancer patients seeking information on side effects of radiotherapy an overview. However, based on the currently low overall quality of websites and the lack of transparency for the average layperson, we emphasize the value of personal contact with the treating radio-oncologist in order to integrate and interpret the information found online.
http://ift.tt/2wiohZB
Side effects of radiotherapy in breast cancer patients
Abstract
Aim
Breast cancer is the most common cancer type among women necessitating adjuvant radiotherapy. As the Internet has become a major source of information for cancer patients, this study aimed to evaluate the quality of websites giving information on side effects of radiotherapy for breast cancer patients.
Methods
A patients' search for the English terms "breast cancer – radiotherapy – side effects" and the corresponding German terms "Brustkrebs – Strahlentherapie – Nebenwirkungen" was carried out twice (5 months apart) using the search engine Google. The first 30 search results each were evaluated using the validated 16-question DISCERN Plus instrument, the Health on the Net Code of Conduct (HONcode) certification and the Journal of the American Medical Association (JAMA) benchmark criteria. The overall quality (DISCERN score) of the retrieved websites was further compared to queries via Bing and Yahoo search engines.
Results
The DISCERN score showed a great range, with the majority of websites ranking fair to poor. Significantly superior results were found for English websites, particularly for webpages run by hospitals/universities and nongovernmental organizations (NGO), when compared to the respective German categories. In general, only a minority of websites met all JAMA benchmarks and was HONcode certified (both languages). We did not determine a relevant temporal change in website ranking among the top ten search hits, while significant variation occurred thereafter. Mean overall DISCERN score was similar between the various search engines.
Conclusion
The Internet can give breast cancer patients seeking information on side effects of radiotherapy an overview. However, based on the currently low overall quality of websites and the lack of transparency for the average layperson, we emphasize the value of personal contact with the treating radio-oncologist in order to integrate and interpret the information found online.
http://ift.tt/2wiohZB
Comparison of the outcomes between thoracoscopic and laparoscopic esophagectomy via retrosternal and prevertebral lifting paths by the same surgeon
Abstract
Background
The objective of the study is to explore the effects of retrosternal and prevertebral lifting paths of the tubular stomach on postoperative complications of patients undergoing cervical anastomosis in thoracoscopic and laparoscopic esophagectomy.
Methods
Sixty-three patients were retrospectively analyzed. The patients received thoracoscopic and laparoscopic esophagectomy by the same surgeon. According to the path by which the stomach was lifted upward, the patients were divided into two groups: the retrosternal path group (32 patients) and the prevertebral path group (31 patients). Operative indications and complications of postoperative patients in these two groups were observed.
Results
There was no statistically significant difference in the time duration of surgery, amount of bleeding, number of dissected lymph node, and postoperative hospitalization time between the retrosternal and prevertebral lifting paths (P > 0.05). Furthermore, the two groups did not show significant difference in the incidence rate of postoperative anastomosis fistula complications (P = 0.702). Instead, the amount of postoperative gastric drainage and the incidence rates of the pulmonary infection were significantly lower in the retrosternal path group than in the prevertebral path group, respectively (P = 0.001, P = 0.012, respectively).
Conclusion
The esophagogastrostomic cervical anastomoses performed via the retrosternal and prevertebral paths are both feasible methods of digestive tract reconstruction. The amount of postoperative gastric drainage volume and the pulmonary infection incidence rate in the retrosternal path group were lower than those in the prevertebral path group. Therefore, gastroesophageal anastomosis via the retrosternal lifting path may be preferably considered for thoracoscopic and laparoscopic surgery for esophageal carcinoma patients.
http://ift.tt/2vrUy1m
Relationship between Physicians' Perceived Stigma toward Depression and Physician Referral to Psycho-oncology services on an Oncology/Hematology Ward.
Abstract
OBJECTIVE
This study was performed to identify relationships between physician's perceived stigma toward depression and psycho-oncology service utilization on an oncology/hematology ward.
METHODS
The study participants were 235 patients in an oncology/hematology ward and 14 physicians undergoing an internal medicine residency training program in Inha University Hospital (Incheon, South Korea). Patients completed the Patient Health Questionnaire-9 (PHQ-9) and residents completed the Perceived Devaluation-Discrimination (PDD) scale that evaluates perceived stigma toward depression. A total PHQ-9 score of ≥5 was defined as clinically significant depression. Physicians decided on referral based on their and patient's opinions. The correlates of physicians' recommendation for referral to psycho-oncology services and real referrals psycho-oncology services were examined.
RESULTS
Of the 235 patients, 143 had PHQ-9 determined depression, and of these 143 patients, 61 received psycho-oncology services. Physician's recommended that 87 patients consult psycho-oncology services. Multivariate analyses showed lower physician's perceived stigma regarding depression was significantly associated with physicians' recommendation for referral, and that real referral to psycho-oncology services was significantly associated with presence of a hematologic malignancy and lower physician's perceived stigma toward depression.
CONCLUSION
Physician's perceived stigma toward depression was found to be associated with real referral to psycho-oncology services and with physician recommendation for referral to psycho-oncology services. Further investigations will be needed to examine how to reduce physicians' perceived stigma toward depression.
http://ift.tt/2vrYH5B
Dural ectasia associated with Mounier-Kuhn syndrome: a novel association in the context of spinal stenosis
We present the case of a patient undergoing lumbar spine decompression for stenosis with a history of Mounier-Kuhn syndrome. The patient presented with axial lumbar spine pain over 6 months with progressive radicular pain to the left L3 dermatome. MRI confirmed spinal stenosis at L3/4 level with associated dural ectasia. The patient had an uneventful spinal decompression with resolution of radicular symptoms and axial spine pain. Dural ectasia poses a significant risk when operating on the lumbosacral spine. Larger cerebrospinal fluid volumes and a capacious dural canal can result in anaesthetic and orthopaedic complications such as inadequate spinal anaesthesia, complicated epidural analgesia, intraoperative dural tears and difficult pedicle screw insertion due to narrow pedicles. This is the first case in the literature detailing the association between dural ectasia and Mounier-Kuhn syndrome. We recommend adequate spinal imaging in patients with Mounier-Kuhn syndrome to exclude dural ectasia prior to undergoing lumbosacral spinal procedures.
http://ift.tt/2wiaGBp
Decreased severity of Shiga toxin-producing Escherichia coli haemolytic uraemic syndrome (STEC-HUS) in a child with type 1 von Willebrand disease
Shiga toxin-producing Escherichia coli-associated haemolytic uraemic syndrome (STEC-HUS) is characterised by haemolytic anaemia, thrombocytopenia and acute kidney injury. Von Willebrand Factor (vWF) is an important mediator of normal thrombi formation and indirect evidence suggests that vWF may play an important role in Shiga toxin-induced thrombi formation. Clinical evidence supporting the role of vWF in STEC-HUS is lacking. A 10-year-old girl with type 1 von Willebrand Disease (vWD) had a mild case of STEC-HUS, with nadir haemoglobin 7.3 g/dL and platelet count 105x109 cells/L and peak serum creatinine 0.56 mg/L and lactate dehydrogenase 741 U/L. This is the first report of STEC-HUS in a patient with vWD. We speculate that the quantitative deficiency of vWF associated with type 1 vWD may have attenuated the course of disease by reducing platelet aggregation, complement activation and thrombi formation. This case adds to a growing literature supporting a link between vWF and STEC-HUS.
http://ift.tt/2xxxT0X
Primary mediastinal seminoma presenting with superior vena caval obstruction
Description
A previously well 29-year-old man presented with a 2-week history of progressive orthopnoea, dry cough, neck and facial swelling, and night sweats. On further questioning, he described 2 kg of weight loss and increasing swallowing difficulties over the previous year. An oesophagogastroduodenoscopy performed 1 year prior was unremarkable. A chest radiograph demonstrated a large mediastinal mass (figure 1A), and a subsequent CT scan revealed a large anterior mediastinal mass measuring 11 cm in diameter. There was central necrosis and complete occlusion of the superior vena cava (SVC; figure 1C,D). An urgent biopsy of the mass was performed, and immunohistochemistry showed malignant cells positive for OCT3/4, placental alkaline phosphatase, D2-40 and CD117 but negative for pancytokeratin, S100, CD30, human chorionic gonadotropin (HCG), alpha-foetoprotein (AFP), CD45, CD20 and CD3. There were no masses found elsewhere on CT imaging of the chest, abdomen, pelvis and head, or on testicular ultrasonography....
http://ift.tt/2wifzuv
Duplex gall bladder: bystander or culprit
Gall bladder (GB) duplication is a rare anatomical malformation, which can be detected by preoperative imaging study. We present a case of duplex gall bladder in a 14-year-old boy who presented with abdominal pain. On ultrasound, he had right nephrolithiasis and duplex gall bladder. Duplex gall bladder was confirmed on MR cholangiopancreatography. There was a dilemma for surgical management of duplex gall bladder; however, he became asymptomatic after conservative treatment. Prophylactic surgery is not recommended for asymptomatic incidentally detected duplex gall bladder. Radiologists and paediatric surgeons should be sensitised about the exact anatomy of this entity.
http://ift.tt/2whxpxp
Neonatal outcomes following exposure in utero to fallout from Chernobyl
Abstract
Iodine 131 (I-131), the principal component of nuclear fallout from the Chernobyl accident, concentrates in the thyroid gland and may pose risks to fetal development. To evaluate this, neonatal outcomes following the accident in April of 1986 were investigated in a cohort of 2582 in utero-exposed individuals from northern Ukraine for whom estimates of fetal thyroid I-131 dose were available. We carried out a retrospective review of cohort members' prenatal, delivery and newborn records. The relationships of dose with neonatal anthropometrics and gestational length were modeled via linear regression with adjustment for potentially confounding variables. We found similar, statistically significant dose-dependent reductions in both head circumference (−1.0 cm/Gy, P = 0.005) and chest circumference (−0.9 cm/Gy, P = 0.023), as well as a similar but non-significant reduction in neonatal length (−0.6 cm/Gy, P = 0.169). Gestational length was significantly increased with increasing fetal dose (0.5 wks/Gy, P = 0.007). There was no significant (P > 0.1) effect of fetal dose on birth weight. The observed associations of radioiodine exposure with decreased head and chest circumference are consistent with those observed in the Japanese in utero-exposed atomic bomb survivors.
http://ift.tt/2xMoQJ1
Sleep duration, mortality and the influence of age
Abstract
Prior work has shown that both short and long sleep predict mortality. However, sleep duration decreases with age and this may affect the relationship of sleep duration with mortality. The purpose of the present study was to assess whether the association between sleep duration and mortality varies with age. Prospective cohort study. 43,863 individuals (64% women), recruited in September 1997 during the Swedish National March and followed through record-linkages for 13 years. Sleep duration was self-reported and measured using the Karolinska Sleep Questionnaire, and grouped into 4 categories: ≤5, 6, 7 (reference) and ≥8 h. Up to 2010 3548 deaths occurred. Multivariable Cox proportional hazards regression models with attained age as time scale were fitted to estimate mortality rate ratios. Among individuals <65 years, short (≤5 h) and long (≥8 h) sleep duration showed a significant relationship with mortality (HR 1.37, 95% CI 1.09–1.71, and HR 1.27, 95% CI 1.08–1.48). Among individuals 65 years or older, no relationships between sleep duration and mortality were observed. The effect of short and long sleep duration on mortality was highest among young individuals and decreased with increasing age. The results suggest that age plays an important role in the relationship between sleep duration and mortality.
http://ift.tt/2wSqtbV
If I had a hammer
Abstract
We present the case of a 64-year-old man who was referred to our service after sustaining a self-inflicted nail-gun injury to his chest. He received three nails penetrated into his chest. Computer tomography revealed no massive haemorrhage or damage to major vessels. He underwent an emergency sternotomy, two nails caused pericardial perforation and myocardial injury were noted easily and removed easily via sternotomy. Myocardial injury showed a trajectory near the junction of the left anterior descending artery and the diagonal artery with no significant bleeding appreciated. The third nail was deep in the lung parenchyma at the hilum. A pacemaker magnet was used to locate the third nail, which was subsequently removed. Our case demonstrates the use of magnets in emergency surgery, to locate and remove metallic foreign bodies.http://ift.tt/2xxPl5x
Successful treatment of aortic root dissection complicated with extensive myocardial infarction using the total artificial heart
Abstract
Acute Type A aortic dissection is a surgical emergency. Urgent repair is indicated to avoid complications such as acute aortic insufficiency, coronary ischemia and aortic rupture with cardiac tamponade. This report details the management of a patient with acute Type A aortic dissection complicated by an extensive anterolateral myocardial infarction and cardiogenic shock who was successfully bridged to transplantation with a total artificial heart.http://ift.tt/2whNkff
Greater saphenous vein anomaly and aneurysm with subsequent pulmonary embolism
Abstract
Venous aneurysms often present as painful masses. They can present either in the deep or superficial venous system. Deep venous system aneurysms have a greater risk of thromboembolism. Though rare, there have been case reports of superficial aneurysms and thrombus causing significant morbidity such as pulmonary embolism. We present a case of an anomalous greater saphenous vein connection with an aneurysm and thrombus resulting in a pulmonary embolism. This is the only reported case of an anomalous greater saphenous vein connection with aneurysm and thrombus, which eventually led to a pulmonary embolism. Recognition of the morbidity and mortality associated with superficial venous aneurysms can help prevent catastrophic outcomes such as pulmonary embolism. Surgical intervention on large symptomatic superficial venous aneurysms may be the optimal treatment in preventing unwanted complications compared to anticoagulation alone.http://ift.tt/2xx5DM1
A marsupialized retrovermian arachnoid cyst and psychotic symptoms
Abstract
In this article, we report a male patient that developed psychotic symptoms after the excision of an arachnoid cyst from the posterior fossa detected by magnetic resonance and subsequent clinical improvement after anti-psychotic treatment.http://ift.tt/2xxJj5c
Pubic and inguinal venous collaterals mimic inguinal hernia
Abstract
Herein we report a case of a 38-year-old men who presented with acute suprapubic pain caused by a tubular, hypoechoic, non-compressible, inguinal mass with no flow evident on color Doppler sonography. The history of the patient, the clinical signs of local inflammation and tenderness on palpation as well as the results of the Doppler ultrasound examination led to the diagnose of an inguinal hernia with bowl incarceration. However, due to a remaining uncertainty whether a bilateral or unilateral hernia was immanent and whether the bowl incarceration was caused by a right or left sided hernia the on-call surgeon initiated a computed tomography (CT) scan. Surprisingly, this CT scan revealed extensive suprapubic venous collaterals with thrombophlebitis that mimicked a bilateral inguinal hernia secondary to an acute unilateral femoral vein thrombosis. Instead of undergoing surgery the patient was treated with antibiotics, pain killer and heparin and was discharged from hospital after 8 days.http://ift.tt/2whQlvW
Stricturoplasty—a bowel-sparing option for long segment small bowel Crohn's disease
Abstract
Stricturoplasty is a surgical option for management of severe stricturing Crohn's disease of the small bowel. It avoids the need for small bowel resection and the associated metabolic complications. This report contrasts the indications and technical aspects of two different stricturoplasty techniques. Case 1 describes an extensive Michelassi (side-to-side isoperistaltic) stricturoplasty performed for a 100 cm segment of diseased small bowel in a 45-year-old patient. Case 2 describes the performance of 12 Heineke-Mikulicz stricturoplasties in a 23-year-old patient with multiple short fibrotic strictures.http://ift.tt/2xxiYnE
Prostaglandin E1 and Its Analog Misoprostol Inhibit Human CML Stem Cell Self-Renewal via EP4 Receptor Activation and Repression of AP-1
Publication date: Available online 30 August 2017
Source:Cell Stem Cell
Author(s): Fengyin Li, Bing He, Xiaoke Ma, Shuyang Yu, Rupali R. Bhave, Steven R. Lentz, Kai Tan, Monica L. Guzman, Chen Zhao, Hai-Hui Xue
Effective treatment of chronic myelogenous leukemia (CML) largely depends on the eradication of CML leukemic stem cells (LSCs). We recently showed that CML LSCs depend on Tcf1 and Lef1 factors for self-renewal. Using a connectivity map, we identified prostaglandin E1 (PGE1) as a small molecule that partly elicited the gene expression changes in LSCs caused by Tcf1/Lef1 deficiency. Although it has little impact on normal hematopoiesis, we found that PGE1 treatment impaired the persistence and activity of LSCs in a pre-clinical murine CML model and a xenograft model of transplanted CML patient CD34+ stem/progenitor cells. Mechanistically, PGE1 acted on the EP4 receptor and repressed Fosb and Fos AP-1 factors in a β-catenin-independent manner. Misoprostol, an FDA-approved EP4 agonist, conferred similar protection against CML. These findings suggest that activation of this PGE1-EP4 pathway specifically targets CML LSCs and that the combination of PGE1/misoprostol with conventional tyrosine-kinase inhibitors could provide effective therapy for CML.
Graphical abstract
Teaser
Xue and colleagues show that prostaglandin E1 (PGE1) inhibits the activity and self-renewal of human CML leukemic stem cells. Combination of PGE1 or an agonist for its receptor EP4 with conventional tyrosine kinase inhibitor treatment can effectively target CML leukemic stem cells and reduce leukemia growth.http://ift.tt/2iIvpcT
Osteoma of the hyoid: an unusual cause of a neck lump
A 65-year-old man with a 2-month history of left-sided neck swelling presented through the cancer pathway. There was no associated 'red flag' symptoms, and clinical examination revealed a left anterior triangle, non-pulsatile firm swelling atypical of a lymph node. Ultrasound scan imaging confirmed a complex structure with an echogenic centre and hypoechoic periphery, which was confirmed on CT as an osteoma of the hyoid.
This is an extremely unusual cause of a neck lump, and an extensive literature review revealed only two previously documented cases.
http://ift.tt/2vruzXW
The protein restriction mimetic Resveratrol is an autophagy inducer stronger than amino acid starvation in ovarian cancer cells
Abstract
The potential benefit of nutrient starvation in the prevention and treatment of cancer is presently under consideration. Resveratrol (RV), a dietary polyphenol acting as a protein (caloric) restriction mimetic, could substitute for amino acid starvation. The effects of starvation and of caloric restriction are mediated, among others, by autophagy, a process that contributes to cell homeostasis by promoting the lysosomal degradation of damaged and redundant self-constituents. Up-regulation of autophagy favors cell survival under nutrient shortage situation, and may drive cancer cells into a non-replicative, dormant state. Both RV and amino acid starvation effectively induced the aminoacid response and autophagy. These processes were associated with inhibition of the mTOR pathway and disruption of the BECLIN1-BCL-2 complex. The number of transcripts positively impinging on the autophagy pathway was higher in RV-treated than in starved cancer cells. Consistent with our data, it appears that RV treatment is more effective than and can substitute for starvation for inducing autophagy in cancer cells. The present findings are clinically relevant because of the potential therapeutic implications. This article is protected by copyright. All rights reserved
http://ift.tt/2xMHj8u
Local infiltration analgesia: a 2-year follow-up of patients undergoing total hip arthroplasty
Abstract
Purpose
Local infiltration analgesia (LIA) is commonly used for postoperative pain management following total hip arthroplasty (THA). However, the long-term effects of the component drugs are unclear. The aim of our study was to investigate functional outcome, quality of life, chronic post-surgical pain, and adverse events in patients within 2 years of undergoing THA.
Methods
The study was a secondary analysis of data from a previous larger study. Eighty patients were randomized to receive either intrathecal morphine (Group ITM) or local infiltration analgesia (Group LIA) for pain management in a double-blind study. The parameters measured were patient-assessed functional outcome [using the Hip dysfunction and Osteo-arthritis Outcome Score (HOOS) questionnaire], health-related quality of life [using the European Quality of Life–5 dimensions (EQ-5D) questionnaire and the 36-Item Short Form Health Survey (SF-36) score], and pain using the numeric rating score (NRS), with persistent post-surgical pain having a NRS of > 3 or a HOOS pain sub-score of > 30. All complications and adverse events were investigated during the first 2 years after primary surgery.
Results
Pain intensity and rescue analgesic consumption were similar between the groups after hospital discharge. No differences were found in HOOS or SF-36 score between the groups up to 6 months after surgery. A significant group × time interaction was seen in the EQ 5D form in favor of the LIA group. No between-group difference in persistent post-surgical pain was found at 3 or 6 months, or in adverse events up to 2 years after surgery.
Conclusion
Analysis of functional outcome, quality of life, and post-discharge surgical pain did not reveal significant differences between patients receiving LIA and those receiving ITM. LIA was found to be a safe technique for THA during the long-term follow-up. However, it should be noted that these conclusions are based on a limited number of patients.
http://ift.tt/2wIEwQL
Breast cancer in Angola, molecular subtypes: a first glance
Fernando Miguel, Lygia Vieira Lopes, Eduardo Ferreira, Emília Ribas, Alexis Fuentes Pelaez, Conceição Leal, Teresina Amaro, Paula Lopes, Cristina Mendes Santos, Carlos Lopes and Lúcio Lara Santos
http://ift.tt/2wSlHem
Postmenopausal mild hirsutism and hyperandrogenemia due to granulosa cell tumor of the ovary: a case report
Among classes of ovarian tumor, granulosa cell tumors are the least common. In approximately 10% of cases of granulosa cell tumor, androgen will be secreted which will present with hirsutism and hyperandrogene...
http://ift.tt/2vrxvUI
D-dimer levels and cerebral infarction in critically ill cancer patients
Abstract
Background
D-dimer levels have been used in the diagnosis of a variety of thrombosis-related diseases. In this study, we evaluated whether measuring D-dimer levels can help to diagnose cerebral infarction (CI) in critically ill cancer patients.
Methods
We retrospectively evaluated all cancer patients who underwent brain magnetic resonance imaging (MRI) between March 2010 and February 2014 at the medical oncology intensive care unit (ICU) of Samsung Medical Center. Brain MRI scanning was performed when CI was suspected due to acute neurological deficits. We compared D-dimer levels between patients ultimately diagnosed as having or not having CI and analyzed diffusion-weighted imaging (DWI) lesion patterns.
Results
A total of 88 patients underwent brain MRI scanning due to clinical suspicion of CI; altered mental status and unilateral hemiparesis were the most common neurological deficits. CI was ultimately diagnosed in 43 (49%) patients. According to the DWI patterns, multiple arterial infarctions (40%) were more common than single arterial infarctions (9%). Cryptogenic stroke etiologies were more common (63%) than determined etiologies. There was no significant difference in D-dimer levels between patients with and without CI (P = 0.319). Although D-dimer levels were not helpful in diagnosing CI, D-dimer levels were associated with cryptogenic etiologies in critically ill cancer patients; D-dimer levels were higher in the cryptogenic etiology group than in the determined etiology group or the non-infarction group (P = 0.001). In multivariate analysis, elevated D-dimer levels (> 8.89 μg/mL) were only associated with cryptogenic stroke (adjusted OR 5.46; 95% confidence interval, 1.876–15.857).
Conclusions
Abnormal D-dimer levels may support the diagnosis of cryptogenic stroke in critically ill cancer patients.
http://ift.tt/2wIPB40
EGFR copy number alterations in primary tumors, metastatic lymph nodes, and recurrent and multiple primary tumors in oral cavity squamous cell carcinoma
Abstract
Background
The EGFR and downstream signaling pathways play an important role in tumorigenesis in oral squamous cell carcinoma (OSCC). Gene copy number alteration is one mechanism for overexpressing the EGFR protein and was also demonstrated to be related to lymph node metastasis, tumor invasiveness and perineural invasion. Therefore, we hypothesized that EGFR gene copy number alteration in the primary tumor could predict amplification in recurrent tumors, lymph node metastatic foci or secondary primary tumors.
Methods
We recruited a group of newly diagnosed OSCC patients (n = 170) between Mar 1997 and Jul 2004. Metastatic lymph nodes were identified from neck dissection specimens (n = 57). During follow-up, recurrent lesions (n = 41) and secondary primary tumors (SPTs, n = 17) were identified and biopsied. The EGFR gene amplifications were evaluated by fluorescence in situ hybridization (FISH) assay in primary tumors, metastatic lymph nodes, recurrences and SPTs.
Results
Of the 170 primary OSCCs, FISH showed low EGFR amplification/polysomy in 19 (11.4%) patients and amplification in 33 (19.8%) patients. EGFR gene amplification was related to lymph node metastasis (χ2 trend test: p = 0.018). Of 57 metastatic lymph nodes, nine (15.8%) had EGFR polysomy and 14 (24.6%) had EGFR gene amplification. The concordance rate of EGFR gene copy number in primary tumors and lymph node metastasis was 68.4% (McNemar test: p = 0.389). Of 41 recurrent tumors, five (12.2%) had EGFR polysomy and five (12.2%) had gene amplification. The concordance rate of EGFR gene copy number between primary tumors and recurring tumors was 65.9% (McNemar test: p = 0.510). The concordance rate between primary tumors and SPTs was 70.6%. EGFR amplification in either primary tumors, metastatic lymph nodes or recurrent tumors had no influence on patient survival.
Conclusion
We can predict two-thirds of the EGFR gene copy number alterations in lymph node metastasis or recurrent tumors from the analysis of primary tumors. For OSCC patients who are unable to provide lymph node or recurrent tumor samples for EGFR gene copy number analysis, examining primary tumors could provide EGFR clonal information in metastatic, recurrent or SPT lesions.
http://ift.tt/2wnxEpp
Is neuron-specific enolase useful for diagnosing malignant pleural effusions? evidence from a validation study and meta-analysis
Abstract
Background
Neuron-Specific enolase (NSE) has been used as a typical tumor marker and shows a potential to diagnose malignant pleural effusion (MPE). The ability of NSE in diagnosing MPE has been investigated in many studies, but with inconsistent conclusions. This study sought to investigate the diagnostic accuracy of NSE for MPE through a clinical study and together with a meta-analysis.
Methods
Pleural effusion samples from 136 patients with MPE and 102 patients with benign pleural effusion (BPE) were collected, and NSE levels were measured by electrochemiluminescence immunoassay. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of NSE to differentiate MPE from BPE. Literature search was conducted to identify suitable publications, data were extracted and diagnostic indexes including sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR) were pooled. Summary ROC curve was generated to determine the overall diagnostic accuracy of NSE for MPE.
Results
Levels of NSE were significantly increased in pleural effusion from patients with MPE than that from BPE (18.53 ± 27.30 vs. 6.41 ± 6.95 ng/ml, p < 0.001). With a cut-off value of 8.92 ng/ml, pleural NSE had a sensitivity of 59.56% and a specificity of 83.33% in diagnosing MPE. A total of 14 studies with 1896 subjects were included for meta-analysis. The diagnostic parameters of NSE were listed as follows: sensitivity, 0.53 (95% CI: 0.38–0.67); specificity, 0.85 (95% CI: 0.75–0.91); PLR, 3.54 (95% CI: 2.33–5.39); NLR, 0.56 (95% CI: 0.42–0.73); and DOR, 6.39 (95% CI: 3.72–10.96). The area under the summary ROC curve was 0.78.
Conclusions
The role of pleural NSE measurement in diagnosing MPE is limited and with a low sensitivity. The clinical utility of NSE assay should be combined with the results of other tumor markers examination and the detail clinical information of patient. Further studies are needed to confirm the role of NSE in diagnosing MPE.
http://ift.tt/2wIXgiP
Putative genomic characteristics of BRAF V600K versus V600E cutaneous melanoma.
Approximately 50% of all cutaneous melanomas harbor activating BRAF V600 mutations; among, these 10-30% carry the V600K mutation. Clinically, patients with V600K tumors experience distant metastases sooner and have an increased risk of relapse and shorter survival than patients with V600E tumors. Despite the clinical and other histopathological differences between these BRAF tumor subtypes, little is known about them at the genomic level. Herein, we systematically compared BRAF V600E and V600K skin cutaneous melanoma (SKCM) samples from the Cancer Genome Atlas (TCGA) for differential protein, gene, and microRNA expression genome-wide using the Mann-Whitney U-test. Our analyses showed that elements of energy-metabolism and protein-translation pathways were upregulated and that proapoptotic pathways were downregulated in V600K tumors compared with V600E tumors. We found that c-Kit protein and KIT gene expressions were significantly higher in V600K tumors than in V600E tumors, concurrent with significant downregulation of several KIT-targeting microRNAs (mir) including mir-222 in V600K tumors, suggesting KIT and mir-222 might be key genomic contributors toward the clinical differences observed. The relationship that we uncovered among KIT/c-Kit expression, mir-222 expression, and growth and prosurvival signals in V600 tumors is intriguing. We believe that the observed clinical aggressiveness of V600K tumors compared to V600E tumors may be attributable to the increased energy metabolism, protein translation and prosurvival signals compared with V600E tumors. If confirmed using larger numbers of V600K tumors, our results may prove useful for designing clinical management and targeted chemotherapeutical interventions for BRAF V600K-positive melanomas. Finally, the small sample size in V600K tumors is a major limitation of our study. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2xx1Xdk
http://ift.tt/2xx1Xdk
Gemcitabine-induced chronic systemic capillary leak syndrome
A 56-year-old woman presented with anasarca, hypoalbuminaemia and hypotension following cycle 3 day 1 of adjuvant gemcitabine for stage II pancreatic cancer. Due to the temporal nature of presentation, suspicion for gemcitabine-induced capillary leak syndrome was included in the differential diagnosis. Vascular endothelial growth factor levels were elevated at 707 pg/mL (reference range: 9–86 pg/mL). Corticosteroids were initiated, resulting in complete resolution of symptoms and hypotension. The patient suffered relapse of symptoms on discontinuation of steroids, further supporting chronic capillary leak syndrome.
http://ift.tt/2wSaNFc
Cyclopia: isolated and with agnathia-otocephaly complex
Cyclopia is a rare form of lethal holoprosencephaly (HPE) due to incomplete cleavage of prosencephalon during embryogenesis, leading to failure of the orbits of the eye to divide into two cavities. We report two cases, one with cyclopia and another case of cyclopia with agnathia–otocephaly complex (AOC). AOC (also known as agnathia–microstomia–synotia syndrome) is a rare lethal congenital malformation of the first branchial arch characterised by the association of agnathia (agenesis of mandible) or mandibular hypoplasia, melotia (anteromedial malposition of ears), microstomia (small mouth), aglossia or microglossia (absent or rudimentary tongue). These two reported cases had in common a single eye and alobar HPE. The first case was live born and the second stillborn. Both mothers did not have antenatal care.
http://ift.tt/2whMPBZ
Significance of multiple preoperative laboratory abnormalities as prognostic indicators in patients with urothelial carcinoma of the upper urinary tract following radical nephroureterectomy
Abstract
Background
The aim of this study was to investigate the prognostic significance of multiple preoperative laboratory abnormalities in upper urinary tract urothelial carcinoma (UUTUC) patients.
Methods
This study included a total of 135 consecutive patients with clinically localized UUTUC who underwent radical nephroureterectomy (RNU). The impact of several preoperative blood-based markers in addition to conventional clinical factors on extravesical recurrence-free survival (eRFS) in these patients was retrospectively evaluated.
Results
Despite the lack of a significant correlation between conventional clinical factors and any of the postoperative pathologic parameters, preoperative laboratory abnormalities were shown to have a significant impact on some pathological factors reflecting an aggressive phenotype as follows—C-reactive protein (CRP) level on pathological stage, De Ritis (aspartate transaminase/alanine transaminase) ratio on nodal involvement, and neutrophil−lymphocyte ratio (NLR) on pathological stage. During the observation period of this study (median 36.1 months), extravesical disease recurrence was detected in 44 (32.6%) of the 135 patients with a 5-year eRFS rate of 62.1%. Of several factors examined, the CRP level, De Ritis ratio, and NRL were significantly correlated with eRFS on univariate analysis. Of these significant factors, the De Ritis ratio and NRL were identified as independent predictors of eRFS on multivariate analysis. Moreover, there were significant differences in eRFS according to the positive numbers of these two independent risk factors.
Conclusions
These findings suggest that it is important to consider laboratory abnormalities, particularly the De Ritis ratio and NLR, to predict disease recurrence following RNU in patients with clinically localized UUTUC.
http://ift.tt/2xMfKf8
Treatment with abiraterone in metastatic castration-resistant prostate cancer patients progressing after docetaxel: a retrospective study.
The aim of this study was to evaluate abiraterone's efficacy in Italian patients affected with metastatic prostate cancer progressing after treatment with docetaxel. We conducted a retrospective analysis of 60 patients. Prostate-specific antigen (PSA) reduction in serum was the primary endpoint for evaluating the efficacy of abiraterone in combination with prednisone treatment, whereas reduced pain, safety, progression-free survival, response rate, and overall survival (OS) were secondary endpoints. A significant correlation was noticed between PSA response and OS. Further, the Index Bravais-Pearson (r) correlation allowed us to observe a significant negative interdependence between PSA response and reduction in pain of 0.57 (95% confidence interval: -0.30 to 0.80) (P=0.005). Meanwhile, regression analysis revealed that PSA levels are predictive of OS. There was a positive correlation with OS, which showed a value of R2 to 0.50 with a slope of 1.44 (P=0.0021). Abiraterone is a well-tolerated and effective treatment modality for patients affected with metastatic castration-resistant prostate cancer. The drug has a better tolerability profile, gives significant pain relief, and increases the survival rate. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2x3iSGp
http://ift.tt/2x3iSGp
Extended topoisomerase 1 inhibition through liposomal irinotecan results in improved efficacy over topotecan and irinotecan in models of small-cell lung cancer.
Liposomal irinotecan (irinotecan liposome injection, nal-IRI), a liposomal formulation of irinotecan, is designed for extended circulation relative to irinotecan and for exploiting discontinuous tumor vasculature for enhanced drug delivery to tumors. Following tumor deposition, nal-IRI is taken up by phagocytic cells followed by irinotecan release and conversion to its active metabolite, SN-38. Sustained inhibition of topoisomerase 1 by extended SN-38 exposure as a result of delivery by nal-IRI is hypothesized to enable superior antitumor activity compared with traditional topoisomerase 1 inhibitors such as conventional irinotecan and topotecan. We evaluated the antitumor activity of nal-IRI compared with irinotecan and topotecan in preclinical models of small-cell lung cancer (SCLC) including in a model pretreated with carboplatin and etoposide, a first-line regimen used in SCLC. Nal-IRI demonstrated antitumor activity in xenograft models of SCLC at clinically relevant dose levels, and resulted in complete or partial responses in DMS-53, DMS-114, and NCI-H1048 cell line-derived models as well as in three patient-derived xenograft models. The antitumor activity of nal-IRI was superior to that of topotecan in all models tested, which generally exhibited limited control of tumor growth and was superior to irinotecan in four out of five models. Further, nal-IRI demonstrated antitumor activity in tumors that progressed following treatment with topotecan or irinotecan, and demonstrated significantly greater antitumor activity than both topotecan and irinotecan in NCI-H1048 tumors that had progressed on previous carboplatin plus etoposide treatment. These results support the clinical development of nal-IRI in patients with SCLC. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://ift.tt/1hexVwJ Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2vDE6Hk
http://ift.tt/2vDE6Hk
Lone Hepatocellular Carcinoma: An Isolated Chest Wall Malignancy
Herein we describe the case of an elderly diabetic gentleman presenting with a two-week history of dyspnea and nonproductive cough, found to have a large left anterolateral chest wall mass. Further characterization through computed tomography (CT) of the chest revealed a soft tissue mass in the left anterior lower hemithorax found to be hepatocellular carcinoma (HCC). The liver, spleen, and pancreas were unremarkable. Diagnostic labs were unremarkable. The patient had no history of hepatitis, alcohol abuse, or illicit substance use. Pathological examination and immunohistochemical staining of the chest mass biopsy were consistent with metastatic hepatocellular carcinoma (HCC). The patient opted to pursue no further medical intervention and expired two weeks later. To the authors' knowledge, this is one of very few descriptions of isolated hepatocellular carcinoma found in the absence of a primary liver lesion and classical risk factors for hepatocarcinogenesis. This case highlights that HCC may present independently of liver lesions seen on imaging in a patient without clear signs or symptoms of liver. HCC should be considered in cases of isolated tumors with unclear primaries as ectopic carcinogenesis and occult primary malignancy are possibilities.
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Alcohol and cigarette consumption as predictors of mortality in patients with head and neck cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium
Abstract
BACKGROUND: Our study evaluated whether demographics, pre-diagnosis lifestyle habits and clinical data are associated with the overall survival (OS) and head and neck cancer (HNC)-specific survival in patients with HNC.PATIENTS AND METHODS: We conducted a pooled analysis, including 4,759 HNC patients from five studies within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Cox proportional Hazard Ratios (HRs) and the corresponding 95% Confidence Intervals (CIs) were estimated including terms reported significantly associated with the survival in the univariate analysis.RESULTS: Five-years OS was 51.4% for all HNC sites combined: 50.3% for oral cavity, 41.1% for oropharynx, 35.0% for hypopharynx and 63.9% for larynx. When we considered HNC-specific survival, 5-year survival rates were 57.4% for all HNC combined, 54.6% for oral cavity, 45.4% for oropharynx, 37.1% for hypopharynx and 72.3% for larynx. Older ages at diagnosis and advanced tumour staging were unfavourable predictors of OS and HNC-specific survival. In laryngeal cancer, low educational level was an unfavourable prognostic factor for OS (HR = 2.54, 95% CI: 1.01-6.38, for high school or lower vs. college graduate), and status and intensity of alcohol drinking were prognostic factors both of the OS (current drinkers HR = 1.73, CI: 1.16-2.58) and HNC-specific survival (current drinkers HR = 2.11, CI: 1.22-3.66). In oropharyngeal cancer, smoking status was an independent prognostic factors for OS. Smoking intensity (>20 cigarettes/day HR = 1.41, CI: 1.03-1.92) was also an independent prognostic factor for OS in patients with cancer of the oral cavity.CONCLUSIONS: OS and HNC-specific survival differ among HNC sites. Pre-diagnosis cigarette smoking is a prognostic factor of the OS for patients with cancer of the oral cavity and oropharynx, while pre-diagnosis alcohol drinking is a prognostic factor of OS and HNC-specific survival for patients with cancer of the larynx. Low educational level is an unfavourable prognostic factor for OS in laryngeal cancer patients.http://ift.tt/2vE1Afw
Tumor Expression of Calcium Sensing Receptor (CASR) and Colorectal Cancer Survival: Results from the Nurses' Health Study and Health Professionals Follow-Up Study
Abstract
Although experimental evidence suggests calcium-sensing receptor (CASR) as a tumor-suppressor, the prognostic role of tumor CASR expression in colorectal carcinoma remains unclear. We hypothesized that higher tumor CASR expression might be associated with improved survival among colorectal cancer patients. We evaluated tumor expression levels of CASR by immunohistochemistry in 809 incident colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. We used Cox proportional hazards regression models to estimate multivariable hazard ratio (HR) for the association of tumor CASR expression with colorectal cancer-specific and all-cause mortality. We adjusted for potential confounders including tumor biomarkers such as microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, expressions of PTGS2, VDR, and CTNNB1, and mutations of KRAS, BRAF, and PIK3CA. There were 240 colorectal cancer-specific deaths and 427 all-cause deaths. The median follow-up of censored patients was 10.8 years (interquartile range: 7.2, 15.1). Compared to patients with no or weak expression of CASR, the multivariable HRs for colorectal cancer-specific mortality were 0.80 [95% confidence interval (CI): 0.55-1.16] in patients with moderate CASR expression, and 0.50 (95% CI: 0.32-0.79) in patients with intense CASR expression (p-trend = 0.003). The corresponding HRs for overall mortality were 0.85 (0.64-1.13) and 0.81 (0.58-1.12), respectively. Higher tumor CASR expression was associated with a lower risk of colorectal cancer-specific mortality. This finding needs further confirmation and if confirmed, may lead to better understanding of the role of CASR in colorectal cancer progression. This article is protected by copyright. All rights reserved.
http://ift.tt/2vqZ3cA
Isoflurane Preconditioning Alleviated Murine Liver Ischemia and Reperfusion Injury by Restoring AMPK/mTOR-Mediated Autophagy.
BACKGROUND: Isoflurane has a pharmacological preconditioning effect against ischemia injury in the heart, kidney, and brain, but whether and how isoflurane preconditioning protects livers against ischemia and reperfusion (IR) injury is unclear. METHODS: Mice were randomly divided into an isoflurane preconditioning (ISO) group and control group, receiving 1.5% isoflurane or carrier gas for 40 minutes, respectively (n = 8/group). A partial warm liver IR model was used, and liver injury was evaluated. Primary hepatocytes were pretreated with 1.5% isoflurane for 2 hours before the induction of cell death by hydrogen peroxide. Cell death and survival were evaluated with the lactate dehydrogenase and cell counting kit-8 assay. Autophagy and regulatory molecules in stressed livers and hepatocytes were analyzed by Western blot (n = 6/group). An autophagy inhibitor (3-methyladenine [3-MA]) and 5' adenosine monophosphate-activated protein kinase (AMPK) inhibitor (dorsomorphin) were administered in vivo (n = 8/group) and in vitro (n = 6/group). RESULTS: Compared to that observed in the control group, mice in the ISO group showed reduced liver injury (alanine aminotransferase [ALT] levels, control versus ISO group, 8285 +/- 769 vs 4896 +/- 917 U/L, P
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http://ift.tt/2wS0xga
Theoretical Modeling of Coagulation Management With Therapeutic Plasma or Prothrombin Complex Concentrate.
Prothrombin complex concentrates (PCCs) have been associated with a possible risk of thromboembolic complications, potentially attributable to an increased ratio of the plasma concentration of factor II (FII) to antithrombin (AT). We developed a mathematical model to examine the relationship between amounts of PCC or therapeutic plasma administered, and plasma levels of FII and AT. The model showed that PCC produces substantial increases in plasma levels of FII but only small changes in AT, increasing the FII:AT ratio. Therapeutic plasma was shown to have only modest effects on levels of FII or AT, unless high doses are used. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. (C) 2017 International Anesthesia Research Society
http://ift.tt/2xMfKfw
http://ift.tt/2xMfKfw
SIRT6 knockout cells resist apoptosis initiation but not progression: a computational method to evaluate the progression of apoptosis
Abstract
Apoptosis is essential for numerous processes, such as development, resistance to infections, and suppression of tumorigenesis. Here, we investigate the influence of the nutrient sensing and longevity-assuring enzyme SIRT6 on the dynamics of apoptosis triggered by serum starvation. Specifically, we characterize the progression of apoptosis in wild type and SIRT6 deficient mouse embryonic fibroblasts using time-lapse flow cytometry and computational modelling based on rate-equations and cell distribution analysis. We find that SIRT6 deficient cells resist apoptosis by delaying its initiation. Interestingly, once apoptosis is initiated, the rate of its progression is higher in SIRT6 null cells compared to identically cultured wild type cells. However, SIRT6 null cells succumb to apoptosis more slowly, not only in response to nutrient deprivation but also in response to other stresses. Our data suggest that SIRT6 plays a role in several distinct steps of apoptosis. Overall, we demonstrate the utility of our computational model to describe stages of apoptosis progression and the integrity of the cellular membrane. Such measurements will be useful in a broad range of biological applications.
http://ift.tt/2wn5kmJ
Comparison of the laryngeal mask airway supreme and the i-gel in paralysed elderly patients: A randomised controlled trial.
BACKGROUND: The laryngeal mask airway supreme (LMA-S) and i-gel are both popular second-generation supraglottic airway devices that have been widely studied in surgical patients, but their differences in clinical performance in the elderly are not clear. OBJECTIVE: We compared the efficacy and safety of the LMA-S and i-gel in anaesthetised and paralysed elderly patients. DESIGN: A prospective, randomised and parallel study. SETTING: Single-centre trial, study period January 2014 from to October 2016. PATIENTS: One hundred and six elderly patients who underwent urological or orthopaedic surgery with an expected duration less than 2 h. INTERVENTION: Patients were allocated to either the LMA-S (n = 53) or i-gel (n = 53) group. All insertions were performed in a standardised manner according to the manufacturers' instructions. MAIN OUTCOME MEASURES: Our primary endpoint was the rate of successful insertion at the first attempt. The adequacy of positive pressure ventilation and airway sealing, fibreoptic laryngoscopy grades and stability of airway maintenance during anaesthesia were also assessed. RESULTS: Although the rate of successful insertion at the first attempt was similar between the two groups (94.3 vs. 82.7%, P = 0.072), more patients required device manipulation during insertion with the LMA-S than the i-gel (42.3 vs. 18.9%, P = 0.011). Good fibreoptic laryngoscopy grades were significantly more common with the i-gel than the LMA-S (79.3 vs. 55.8%, P = 0.042), and peak inspiratory pressures were lower in the i-gel group both immediately after insertion and at the end of surgery. Leak pressures were significantly higher in the i-gel group than the LMA-S group, both immediately after insertion and at the end of surgery (25.8 vs. 23.0, P = 0.036; and 28.1 vs. 23.7, P
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http://ift.tt/2x3zjm7
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