Valutazione preoperatoria dell’estensione di malattia in pazienti affette da carcinoma della mammella con Tomosintesi Digitale Mammaria e Risonanza Magnetica: confronto tra metodiche

OBIETTIVI Confrontare le potenzialità diagnostiche della TDM e della RM nella valutazione pre-operatoria dell’estensione tumorale, rispetto all’esame istologico definitivo che abbiamo utilizzato come gold standard, in pazienti affette da neoplasia mammaria recentemente diagnosticata istologicamente. MATERIALI E METODI Da Maggio 2014 a Aprile 2016, 50 pazienti (età media 54.9) hanno eseguito un esame RM utilizzando l’apparecchio a 3T (GE Discovery MR750) con bobina e protocollo dedicati per lo studio della mammella ed due proiezioni di TDM acquisite con il mammografo Mammomat Inspiration di Siemens. Un lettore, con 15 anni di esperienza in imaging senologico, ha valutato ogni singolo caso con un intervallo di tempo di 2-4 settimane tra la lettura delle due metodiche. Sono stati calcolati sensibilità, valore predittivo positivo (VPP) e accuratezza di RM e TDM. E’ stato utilizzato il test McNemar per confrontare la sensibilità di RM e TDM. Sono stati utilizzati un test di correlazione (Pearson) ed un’analisi di regressione per valutare la corrispondenza delle misurazioni delle lesioni alla RM vs l’istologico, TDM vs l’istologico ed RM vs la TDM. Un’analisi di regressione separata è stata condotta per studiare in particolare le lesioni mass e non-mass. Infine, è stato applicato un modello logistico sui casi positivi per valutare la detection rate della TDM rispetto alla densità del seno ed alla dimensione della lesione. RISULTATI La sensibilità della RM è risultata del 100%, il VPP 96% e l’accuratezza 96%. Il coefficiente di correlazione lineare di Pearson della RM vs Esame Istologico è stato di 0.97 (p-value < 0.0001), il coefficiente di regressione è stato pari a 1 (R-squared = 0.96). La sensibilità della TDM è risultata 81%, il VPP 92% e l’accuratezza 77%. Il coefficiente di correlazione lineare di Pearson della TDM vs esame istologico è stato di 0.92 (p-value<0.0001). Il coefficiente di regressione si è rivelato pari a 0,8 (R-squared = 0,85). La differenza di sensibilità tra RM e TDM si è dimostrata statisticamente significativa (Mc Nemar p-value <0,001). Il coefficiente di regressione si è rivelato pari a 0,83 (R-squared = 0,86). Dividendo i casi veri positivi in due gruppi (lesioni mass e non mass) abbiamo riscontrato che la variabilità dell'errore con cui la RM misura il diametro della lesione è risultata significativamente minore per il campione mass, suggerendo una valutazione più accurata in questo gruppo di lesioni. Per quanto riguarda la TDM abbiamo dimostrato che non c’è una riduzione significativa della variabilità dell'errore in entrambi i gruppi (mass e non-mass). CONCLUSIONI La RM si è confermata la metodica migliore nella stadiazione preoperatoria in termini di sensibilità, VPP e accuratezza ; tuttavia la TDM ha ottenuto dei risultati soddisfacenti, stimando quasi correttamente le dimensioni delle lesioni. Nei casi in cui siano controindicazioni o impossibilità ad effettuare un esame di risonanza magnetica quindi, la TDM potrebbe essere considerata come valida alternativa nella stadiazione preoperatoria del carcinoma mammario.OBJECTIVES To prospectively evaluate the accuracy in tumor extent and size assessment of Digital Breast Tomosynthesis (DBT) and Magnetic Resonance Imaging (MRI) in women with known breast cancers, with pathological size as the gold standard. MATERIALS AND METHODS From May 2014 to April 2016, 50 patients with known breast cancer were enrolled in our prospective study. All patients provided written informed consent and underwent MR on a 3T magnet and DBT projections. Two radiologists, with 15 and 7 years of experience in breast imaging, evaluated in consensus each imaging set unaware of the final histological examination. MR and DBT sensitivity, positive predictive value (PPV) and accuracy were calculated, using histology as the gold standard. McNemar test was used to compare MR and DBT sensitivity. Correlation and regression analyses was used to evaluate concordance of MR vs Histology, DBT vs Histology and MR vs DBT lesions tumor size and their dependence with respect to the histological results. Measurements were considered concordant if they were within ±3 mm. Separate regression analyses was used to investigate the effect of mass or nonmass enhancement. Finally a logistic model was fitted to the positive cases to evaluate the DBT detection rate with respect to breast density, the lesion size and other covariates. RESULTS On histological examination 70 lesions were detected. MR had a sensitivity of 100%, PPV 96% and accuracy 96%; DBT sensitivity was 81%, PPV 92% and accuracy 77%. McNemar test p-value was 0.0003. Lesions size correlation coefficient was 0.97 for MR vs Histology, 0.92 for DBT vs Histology. The regression coefficient for MR vs DBT was 0.83. A separate regression models fitted to the mass or non-mass enhancement showed a smaller error variability into the mass group, suggesting a more accurate measurement of lesions with a mass morphology. Regarding the evaluation of lesion detection rate and size on DBT, we found a lower detection rate and an higher relative error in patients with dense breasts, in particular for small lesions. In case of large lesions DBT performed similarly in both dense and fatty breasts . CONCLUSIONS MR provided higher diagnostic performance than DBT in pre-operative evaluation of disease, even if DBT showed good accuracy, sensitivity and accurate tumor size assessment. Therefore DBT could be a valid tool for preoperative staging when MR could not be performed

Intraindividual Comparison of Gadoxetate Disodium–enhanced MR Imaging and 64-Section Multidetector CT in the Detection of Hepatocellular Carcinoma in Patients with Cirrhosis

Our study demonstrates that, compared with multiphasic 64-section multidetector CT, gadoxetate disodium–enhanced MR imaging yields significantly higher diagnostic accuracy and sensitivity for the detection of hepatocellular carcinoma in patients with cirrhosis (P = .001 for both comparisons)

Lack of atorvastatin protective effect against atrial fibrillation in CETP TaqIB2B2 genotype.

none3noGalati, Francesca; Galati, Antonio; Massari, SerafinaGalati, Francesca; Galati, Antonio; Massari, Serafin

Breast cancer screening programs: does one risk fit all?

Comment on Risk-Adapted Starting Age of Screening for Relatives of Patients With Breast Cancer. [JAMA Oncol. 2019

A role for Separase in telomere protection

Drosophila telomeres are elongated by transposition of specialized retroelements rather than telomerase activity and are assembled independently of the sequence. Fly telomeres are protected by the terminin complex that localizes and functions exclusively at telomeres and by non-terminin proteins that do not serve telomere-specific functions. We show that mutations in the Drosophila Separase encoding gene Sse lead not only to endoreduplication but also telomeric fusions (TFs), suggesting a role for Sse in telomere capping. We demonstrate that Separase binds terminin proteins and HP1, and that it is enriched at telomeres. Furthermore, we show that loss of Sse strongly reduces HP1 levels, and that HP1 overexpression in Sse mutants suppresses TFs, suggesting that TFs are caused by a HP1 diminution. Finally, we find that siRNA-induced depletion of ESPL1, the Sse human orthologue, causes telomere dysfunction and HP1 level reduction in primary fibroblasts, highlighting a conserved role of Separase in telomere protection

Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use

<p>Abstract</p> <p>Background</p> <p>Resveratrol is a non flavonoid polyphenol compound present in many plants and fruits and, at especially high concentrations, in the grape berries of <it>Vitis vinifera</it>. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed its ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. The results presented here show an evident toxic activity of the drug at high concentrations, on the other hand at sub-cytotoxic concentrations, resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA.</p> <p>Methods</p> <p>The mouse fibroblast line 3T6 and the human tumor line HL60 were used throughout the work. Cell viability and vital cell count were assessed respectively, by the MTT assay and Trypan Blue staining. Cytotoxic properties and evaluation of viral DNA production by agarose gel electrophoresis were performed according to standard protocols.</p> <p>Results</p> <p>Our results show a clear dose dependent both cytotoxic and antiviral effect of resveratrol respectively at high and low concentrations. The cytotoxic action is exerted towards a stabilized cell-line (3T6) as well as a tumor-line (HL60). Furthermore the antiviral action is evident after the phase of virion entry, therefore data suggest that the drug acts during the synthesis of the viral progeny DNA.</p> <p>Conclusion</p> <p>Resveratrol is cytotoxic and inhibits, in a dose dependent fashion, the synthesis of polyomavirus DNA in the infected cell. Furthermore, this inhibition is observed at non cytotoxic concentrations of the drug. Our data imply that cyto-toxicity may be attributed to the membrane damage caused by the drug and that the transfer of polyomavirus from the endoplasmic reticulum to the cytoplasm may be hindered. In conclusion, the cytotoxic and antiviral properties of resveratrol make it a potential candidate for the clinical control of proliferative as well as viral pathologies.</p

Can MRI biomarkers predict triple-negative breast cancer?

The purpose of this study was to investigate MRI features of triple-negative breast cancer (TNBC) compared with non-TNBC, to predict histopathological results. In the study, 26 patients with TNBC and 24 with non-TNBC who underwent multiparametric MRI of the breast on a 3 T magnet over a 10-months period were retrospectively recruited. MR imaging sets were evaluated by two experienced breast radiologists in consensus and classified according to the 2013 American College of Radiology (ACR) BI-RADS lexicon. The comparison between the two groups was performed using the Chi-square test and followed by logistic regression analyses. We found that 92% of tumors presented as mass enhancements (p = 0.192). 41.7% of TNBC and 86.4% of non-TNBC had irregular shape (p = 0.005); 58.3% of TNBC showed circumscribed margins, compared to 9.1% of non-TNBC masses (p = 0.001); 75% of TNBC and 9.1% of non-TNBC showed rim enhancement (p &lt; 0.001). Intralesional necrosis was significantly associated with TNBC (p = 0.016). Rim enhancement and intralesional necrosis risulted to be positive predictors at univariate analysis (OR = 29.86, and 8.10, respectively) and the multivariate analysis confirmed that rim enhancement is independently associated with TNBC (OR = 33.08). The mean ADC values were significantly higher for TNBC (p = 0.011). In conclusion, TNBC is associated with specific MRI features that can be possible predictors of pathological results, with a consequent prognostic value

Effect of the lemon essential oils on the safety and sensory quality of salted sardines (Sardina pilchardus Walbaum 1792)

The main aim of this research was to investigate the biopreservative effects of lemon essential oil (EO) micro-emulsions on salted sardines. The experimental design included two experimental trials, SR1 and SR2 carried out with 25&nbsp;ml of lemon EO micro-emulsion at 0.3 and 1.0% (v/v), respectively, and a control trial performed without EO addition. Chemical analyses on salted sardines inoculated with the EOs clearly showed a substantial persistence of several volatile organic compounds (VOCs) belonging to groups of monoterpene hydrocarbons, oxygenated monoterpenes and sesquiterpene hydrocarbons derived from EOs during the entire period of ripening. In particular, the molecules mostly represented were limonene, p-cymene and β-pinene. Immediately after the addition of EOs, the concentrations of all microbial groups decreased. The presence of Enterobacteriaceae, staphylococci and rod lactic acid bacteria (LAB) observed in the trials SR1 and SR2 was significantly lower than that registered for the control trial during the entire period of monitoring. Furthermore, the addition of EOs determined a lower accumulation of histamine in sardines compared to those of the control trial. The highest scores of sensory evaluation were registered for flavour and overall acceptability of the experimental trials in presence of EOs. On the basis of the increasing interest toward novel food preservatives, we conclude that the use of EOs to produce salted fishes represents a valid strategy to improve safety and sensory characteristics of salted sardines. This work has also economic implications, since the flavour improvement due to the addition of lemon EOs might increase the consumption of sardines by regular and new consumers

Genotoxicity Revaluation of Three Commercial Nitroheterocyclic Drugs: Nifurtimox, Benznidazole, and Metronidazole

Nitroheterocyclic compounds are widely used as therapeutic agents against a variety of protozoan and bacterial infections. However, the literature on these compounds, suspected of being carcinogens, is widely controversial. In this study, cytotoxic and genotoxic potential of three drugs, Nifurtimox (NFX), Benznidazole (BNZ), and Metronidazole (MTZ) was re-evaluated by different assays. Only NFX reduces survival rate in actively proliferating cells. The compounds are more active for base-pair substitution than frameshift induction in Salmonella; NFX and BNZ are more mutagenic than MTZ; they are widely dependent from nitroreduction whereas microsomal fraction S9 weakly affects the mutagenic potential. Comet assay detects BNZ- and NFX-induced DNA damage at doses in the range of therapeutically treated patient plasma concentration; BNZ seems to mainly act through ROS generation whereas a dose-dependent mechanism of DNA damaging is suggested for NFX. The lack of effects on mammalian cells for MTZ is confirmed also in MN assay whereas MN induction is observed for NFX and BNZ. The effects of MTZ, that shows comparatively low reduction potential, seem to be strictly dependent on anaerobic/hypoxic conditions. Both NFX and BNZ may not only lead to cellular damage of the infective agent but also interact with the DNA of mammalian cells

Design, synthesis, ADME and biological evaluation of benzylpiperidine and benzylpiperazine derivatives as novel reversible monoacylglycerol lipase (MAGL) inhibitors.

The degradation of the endocannabinoid 2-arachidonoylglycerol is mediated by the enzyme monoacylglycerol lipase (MAGL), thus generating arachidonic acid, the precursor of prostaglandins and other pro-inflammatory mediators. MAGL also contributes to the hydrolysis of monoacylglycerols into glycerol and fatty acids in peripheral body districts, which may act as pro-tumorigenic signals. For this reason, MAGL inhibitors have been considered as interesting therapeutic agents for their anti-nociceptive, anti-inflammatory, antioxidant and anti-cancer properties. So far, only a limited series of reversible MAGL inhibitors, which are devoid of side effects shown by irreversible inhibitors in animal models, have been reported. Here we optimized a class of benzylpiperidine and benzylpiperazine-based compounds for a reversible MAGL inhibition. The best MAGL inhibitors of this class, compounds 28 and 29, showed a very good inhibition potency, both on the isolated enzyme and in U937 cells, as confirmed by molecular modeling studies that predicted their binding mode into the MAGL active site. Both compounds are characterized by a high selectivity for MAGL versus other serine hydrolases including enzymes of the endocannabinoid system, as confirmed by ABPP experiments in mouse brain membranes. Moreover, very good properties concerning ADME parameters and low in vivo toxicity have been observed for both compounds