Incorporation of the technologist’s opinion for arbitration of discrepant assessments among radiologists at screening mammography

Abstract

Purpose

We determined whether the addition of the technologist's opinion may be helpful in deciding if discordant readings at blinded double reading should be recalled.

Methods

A consecutive series of 99,013 digital screening mammograms, obtained between July 2013 and January 2015, were included. All mammograms were first interpreted by a technologist and then double read in a blinded fashion by a team of 13 screening radiologists. All concordant and discordant positive readings among radiologists were recalled.

Results

Out of 3562 recalls, 998 women were recalled after a discordant reading. Of these women, 337 (33.8%) had a positive technologist assessment, of which 40 (11.9%) were diagnosed with breast cancer. Sixty women with a negative technologist assessment (60/661, 9.1%) were diagnosed with breast cancer (p = 0.16). Recall rate would have decreased with technologist arbitration (3.6% vs. 2.9%, p < 0.001). Cancer detection rate decreased with 8.5%, from 7.1/1000 screens to 6.5/1000 screens (p = 0.10). Among women with a positive technologist assessment, the probability of breast cancer was highest in case of suspicious microcalcifications and lowest for suspicious masses (30.4% (17/56) versus 7.0% (16/212), p < 0.001). Breast cancers were diagnosed in all groups of mammographic abnormalities, except in women with a suspicious asymmetry and a negative technologist assessment.

Conclusions

Assessment by a technologist does not provide a significant discriminating ability in case of a discordant radiologist reading and, taking into account the decrease in cancer detection rate, does not appear to be a suitable arbitration strategy for discordant recalls at blinded double reading.

https://ift.tt/2HRf69Y

Cancers, Vol. 10, Pages 133: Translation Control by p53

Cancers, Vol. 10, Pages 133: Translation Control by p53

Cancers doi: 10.3390/cancers10050133

Authors: Justina Kasteri Dibash Das Xuelin Zhong Leah Persaud Ashleigh Francis Hilal Muharam Moira Sauane

The translation of mRNAs plays a critical role in the regulation of gene expression and therefore, in the regulation of cell proliferation, differentiation and apoptosis. Unrestricted initiation of translation causes malignant transformation and plays a key role in the maintenance and progression of cancers. Translation initiation is regulated by the ternary complex and the eukaryotic initiation factor 4F (eIF4F) complex. The p53 tumor suppressor protein is the most well studied mammalian transcription factor that mediates a variety of anti-proliferative processes. Post-transcriptional mechanisms of gene expression in general and those of translation in particular play a major role in shaping the protein composition of the cell. The p53 protein regulates transcription and controls eIF4F, the ternary complex and the synthesis of ribosomal components, including the down-regulation of rRNA genes. In summary, the induction of p53 regulates protein synthesis and translational control to inhibit cell growth.

https://ift.tt/2FKDUuj

Cancers, Vol. 10, Pages 134: The Prevalence of CD146 Expression in Breast Cancer Subtypes and Its Relation to Outcome

Cancers, Vol. 10, Pages 134: The Prevalence of CD146 Expression in Breast Cancer Subtypes and Its Relation to Outcome

Cancers doi: 10.3390/cancers10050134

Authors: Ingeborg E. de Kruijff Anna M. Timmermans Michael A. den Bakker Anita M.A.C. Trapman-Jansen Renée Foekens Marion E. Meijer-Van Gelder Esther Oomen-de Hoop Marcel Smid Antoinette Hollestelle Carolien H.M. van Deurzen John A. Foekens John W.M. Martens Stefan Sleijfer

CD146, involved in epithelial-to-mesenchymal transition (EMT), might affect cancer aggressiveness. We here investigated the prevalence of CD146 expression in breast cancer subtypes, its relation to prognosis, the relation between CD146 and EMT and the outcome to tamoxifen. Primary breast cancer tissues from 1342 patients were available for this retrospective study and immunohistochemically stained for CD146. For survival analyses, pure prognosis was studied by only including lymph-node negative patients who did not receive (neo)adjuvant systemic treatment (n = 551). 11% of the tumors showed CD146 expression. CD146 expression was most prevalent in triple-negative cases (64%, p &lt; 0.001). In univariable analysis, CD146 expression was a prognostic factor for both metastasis-free survival (MFS) (p = 0.020) and overall survival (OS) (p = 0.037), but not in multivariable analysis (including age, tumor size, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67). No correlation between CD146 and EMT nor difference in outcome to first-line tamoxifen was seen. In this large series, our data showed that CD146 is present in primary breast cancer and is a pure prognostic factor for MFS and OS in breast cancer patients. We did not see an association between CD146 expression and EMT nor on outcome to tamoxifen.

https://ift.tt/2roVYoz

Gene therapy knockdown of VEGFR2 in retinal endothelial cells to treat retinopathy

Abstract

Inhibition of vascular endothelial growth factor (VEGF) in retinopathy of prematurity (ROP) raises concerns for premature infants because VEGF is essential for retinovascular development as well as neuronal and glial health. This study tested the hypothesis that endothelial cell-specific knockdown of VEGF receptor 2 (VEGFR2), or downstream STAT3, would inhibit VEGF-induced retinopathy without delaying physiologic retinal vascular development. We developed an endothelial cell-specific lentiviral vector that delivered shRNAs to VEGFR2 or STAT3 and a green fluorescent protein reporter under control of the VE-cadherin promoter. The specificity and efficacy of the lentiviral vector-driven shRNAs were validated in vitro and in vivo. In the rat oxygen-induced retinopathy model highly representative of human ROP, the effects of endothelial cell knockdown of VEGFR2 or STAT3 were determined on intravitreal neovascularization (IVNV), physiologic retinal vascular development [assessed as area of peripheral avascular/total retina (AVA)], retinal structure, and retinal function. Targeted knockdown of VEGFR2 or STAT3 specifically in retinal endothelial cells by subretinal injection of lentiviral vectors into postnatal day 8 rat pup eyes efficiently inhibited IVNV, and knockdown of VEGFR2 also reduced AVA and increased retinal thickness without altering retinal function. Taken together, our results support specific knockdown of VEGFR2 in retinal endothelial cells as a novel therapeutic method to treat retinopathy.

https://ift.tt/2JXanQH

DNA methylation-based reclassification of olfactory neuroblastoma

Abstract

Olfactory neuroblastoma/esthesioneuroblastoma (ONB) is an uncommon neuroectodermal neoplasm thought to arise from the olfactory epithelium. Little is known about its molecular pathogenesis. For this study, a retrospective cohort of n = 66 tumor samples with the institutional diagnosis of ONB was analyzed by immunohistochemistry, genome-wide DNA methylation profiling, copy number analysis, and in a subset, next-generation panel sequencing of 560 tumor-associated genes. DNA methylation profiles were compared to those of relevant differential diagnoses of ONB. Unsupervised hierarchical clustering analysis of DNA methylation data revealed four subgroups among institutionally diagnosed ONB. The largest group (n = 42, 64%, Core ONB) presented with classical ONB histology and no overlap with other classes upon methylation profiling-based t-distributed stochastic neighbor embedding (t-SNE) analysis. A second DNA methylation group (n = 7, 11%) with CpG island methylator phenotype (CIMP) consisted of cases with strong expression of cytokeratin, no or scarce chromogranin A expression and IDH2 hotspot mutation in all cases. T-SNE analysis clustered these cases together with sinonasal carcinoma with IDH2 mutation. Four cases (6%) formed a small group characterized by an overall high level of DNA methylation, but without CIMP. The fourth group consisted of 13 cases that had heterogeneous DNA methylation profiles and strong cytokeratin expression in most cases. In t-SNE analysis, these cases mostly grouped among sinonasal adenocarcinoma, squamous cell carcinoma, and undifferentiated carcinoma. Copy number analysis indicated highly recurrent chromosomal changes among Core ONB with a high frequency of combined loss of chromosome 1–4, 8–10, and 12. NGS sequencing did not reveal highly recurrent mutations in ONB, with the only recurrently mutated genes being TP53 and DNMT3A. In conclusion, we demonstrate that institutionally diagnosed ONB are a heterogeneous group of tumors. Expression of cytokeratin, chromogranin A, the mutational status of IDH2 as well as DNA methylation patterns may greatly aid in the precise classification of ONB.

https://ift.tt/2rmz8Om

A Comparative Study of Iodized Salt Programs: Shanghai and Switzerland

Abstract

Both Shanghai and Switzerland are developed regions with long-standing salt iodization programs and periodic monitoring. However, the two regions have their own approach to the implementation of the iodized salt policy. In Shanghai, monitoring was carried out every few years, using probability-proportional-to-size sampling technique to select 30 sampling units. Each unit consisted of more than 12 pregnant women and one randomly selected primary school. Urine samples were then taken from the chosen pregnant women and randomly recruited students of that school for iodine test. Data of Switzerland used in this comparative study was extracted from published researches. In Shanghai, the median urinary iodine concentration (UIC) in 2014 was 20% lower than in 1999 (P < 0.05). The median UIC of pregnant women in 2014 was 9.5% lower than that in 2011 (P < 0.05). In terms of iodized salt concentration, opposite to the increasing in Switzerland, it has exhibited a downward trend in Shanghai (P < 0.05). For the years monitored, the iodized salt concentration in Shanghai was significantly (P < 0.05) higher than in Switzerland. Though the UIC of children exhibited a downward trend in Shanghai (P < 0.05), it was still significantly (P < 0.05) higher than in Switzerland over the same monitoring period. However, the UIC in pregnant women was a totally different story, which was significantly (P < 0.05) lower in Shanghai than in Switzerland. Iodized salt is very important for maintaining sufficient iodine level in the population. Appropriate concentration of iodine in fortified salt needs to be decided according to local conditions. Special attention should be paid to the iodine level of pregnant women in Shanghai, and more education about iodine is necessary for the public health.

https://ift.tt/2FLyE9J

Baseline health indicators of Eastern Pacific Green Turtles ( Chelonia mydas ) from Baja California Sur, Mexico

Abstract

Sea turtle health is an important component of conservation since these taxa is susceptible to infectious diseases that can cause illness leading to mortality. Threats to the health, survival, and reproduction of sea turtles are increasingly documented; however, prevention and control has not yet been successfully achieved. Thus, information about health indicators of sea turtles is a useful tool in order to achieve the best possible conservation measures. The objective of this study was to establish a baseline of health indicators of free-ranging Eastern Pacific green turtles (Chelonia mydas) from neritic foraging and juvenile developmental habitats in Baja California Sur. Here, we contribute baseline and reference interval values of vital signs, complete blood count, and plasma blood chemistry for live specimens from coastal lagoons: Ojo de liebre and San Ignacio in Baja California Sur, Mexico. With the integration of these indicators, 79 turtles were diagnosed as "healthy." Development of site-specific baseline of health indicators for free-ranging sea turtle populations allows to infer that the habitat provides adequate conditions for these species to carry out the activities corresponding to their stage of development and helps to create the management plans and pertinent conservation strategies as well as for the organisms in the area.

https://ift.tt/2jwXaTa