Focal therapy for prostate cancer: Evolutionary parallels to breast cancer treatment. Letter.

To the Editor:We read with great interest the recentmanuscript by Labbate et al reviewing the develop-ment of focal therapy in breast and prostate cancer(PCa).1Breast focal therapy (bFT) represents a suc-cessful model for organ-sparing cancer treatment, soas urologists sensible to prostate focal therapy (pFT)we can learn much about the complex process of bFTrecognition by the scientific community

Molecular Insights into Division of Single Human Cancer Cells in On-Chip Transparent Microtubes.

In vivo, mammalian cells proliferate within 3D environments consisting of numerous microcavities and channels, which contain a variety of chemical and physical cues. External environments often differ between normal and pathological states, such as the unique spatial constraints that metastasizing cancer cells experience as they circulate the vasculature through arterioles and narrow capillaries, where they can divide and acquire elongated cylindrical shapes. While metastatic tumors cause most cancer deaths, factors impacting early cancer cell proliferation inside the vasculature and those that can promote the formation of secondary tumors remain largely unknown. Prior studies investigating confined mitosis have mainly used 2D cell culture systems. Here, we mimic aspects of metastasizing tumor cells dividing inside blood capillaries by investigating single-cell divisions of living human cancer cells, trapped inside 3D rolled-up, transparent nanomembranes. We assess the molecular effects of tubular confinement on key mitotic features, using optical high- and super-resolution microscopy. Our experiments show that tubular confinement affects the morphology and dynamics of the mitotic spindle, chromosome arrangements, and the organization of the cell cortex. Moreover, we reveal that membrane blebbing and/or associated processes act as a potential genome-safety mechanism, limiting the extent of genomic instability caused by mitosis in confined circumstances, especially in tubular 3D microenvironments. Collectively, our study demonstrates the potential of rolled-up nanomembranes for gaining molecular insights into key cellular events occurring in tubular 3D microenvironments in vivo.The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 311529 (S.S.) and the Volkswagen Foundation no. 86 362 (S.S. and W.X.), a FEBS Return-to-Europe fellowship (C.K.S.), the Wellcome Trust (092096/Z/10/Z for N.L.; 094587/Z/10/Z for R.B.), and a European Research Council (ERC) Starting Researcher Grant (R.E.C.-S.; SYSGRO). O.G.S. acknowledges financial support from the DFG Research Unit 1713 “Sensorische Mikro und Nanosysteme”. D.H.G. acknowledges funding from the Alexander von Humboldt Foundation and the U.S. National Science Foundation (Grants: CMMI 1200241 and CBET-1442014). Research in the S.P.J. laboratory is funded by Cancer Research U.K., the ERC, and the European Community Seventh Framework Programme (DDResponse), with core infrastructure provided by Cancer Research U.K. and the Wellcome Trust.This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/acsnano.6b0046

High mammographic density in long-term night shift workers: DDM-Spain /Var-DDM

[EN] Background: Night-shift work (NSW) has been suggested as a possible cause of breast cancer, and its association with mammographic density (MD), one of the strongest risk factors for breast cancer, has been scarcely addressed. This study examined NSW and MD in Spanish women. Methods: The study covered 2,752 women aged 45-68 years recruited in 2007-2008 in 7 population-based public breast cancer screening centers, which included 243 women who had performed NSW for at least one year. Occupational data and information on potential confounders were collected by personal interview. Two trained radiologist estimated the percentage of MD assisted by a validated semiautomatic computer tool (DM-scan). Multivariable mixed linear regression models with random screening center-specific intercepts were fitted using log-transformed percentage of MD as the dependent variable and adjusting by known confounding variables. Results: Having ever worked in NSW was not associated with MD [e(beta):0.96; 95% confidence interval (CI), 0.86-1.06]. However, the adjusted geometric mean of the percentage of MD in women with NSW for more than 15 years was 25% higher than that of those without NSW history (MD>15 (years):20.7% vs. MDnever:16.5%; e(beta):1.25; 95% CI, 1.01-1.54). This association was mainly observed in postmenopausal participants (e(beta):1.28; 95% CI, 1.00-1.64). Among NSW-exposed women, those with <= 2 night-shifts per week had higher MD than those with 5 to 7 nightshifts per week (e(beta):1.42; 95% CI, 1.10-1.84). Conclusions: Performing NSW was associated with higherMD only in women with more than 15 years of cumulated exposure. These findings warrant replication in futures studies. (C)2017 AACR.We would like to thank the participants in the DDM-Spain/Var-DDM-Spain study for their contribution to breast cancer research. Other members of DDM-Spain/Var-DDM: Gonzalo. López-Abente, Roberto Pastor-Barriuso, Pablo Fernández-Navarro, Anna Cabanes, Soledad Laso, Manuela Alcaraz, María Casals, Inmaculada Martínez, Juan Carlos Pérez Cortés, Joaquín Antón, Nieves Ascunce, Isabel González-Román, Ana Belén Fernández, Montserrat Corujo, Soledad Abad, and Jesús Vioque. A.M. Pedraza-Flechas FI14CIII/00013 PFIS; B. Perez-Gomez FIS PS09/0790; M. Pollán FIS PI060386, EPY1306/06 collaboration agreement between Astra-Zeneca and ISCIII, and FECMA 485 EPY 1170 10; R. LLobet Gent per Gent Fund (EDEMAC Project); All authors: European Regional Development Fund (FEDER). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.Pedraza-Flechas, AM.; Lope, V.; Sanchez-Contador, C.; Santamarina, C.; Pedraz-Pingarron, C.; Moreo, P.; Ederra, M.... (2017). High mammographic density in long-term night shift workers: DDM-Spain /Var-DDM. Cancer Epidemiology Biomarkers & Prevention. 26(6):905-913. https://doi.org/10.1158/1055-9965.EPI-16-0507S90591326

Overeating, caloric restriction and mammographic density in Spanish women. DDM-Spain study

[EN] Objectives: Mammographic density (MD) is a strong risk factor for breast cancer. The present study evaluates the association between relative caloric intake and MD in Spanish women. Study design: We conducted a cross-sectional study in which 3517 women were recruited from seven breast cancer screening centers. MD was measured by an experienced radiologist using craniocaudal mammography and Boyd's semi-quantitative scale. Information was collected through an epidemiological survey. Predicted calories were calculated using linear regression models, including the basal metabolic rate and physical activity as explanatory variables. Overeating and caloric restriction were defined taking into account the 99% confidence interval of the predicted value. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using center-specific mixed ordinal logistic regression models, adjusted for age, menopausal status, body mass index, parity, tobacco use, family history of breast cancer, previous biopsies, age at menarche and adherence to a Western diet. Main outcome measure: Mammographic density. Results: Those women with an excessive caloric intake ( > 40% above predicted) presented higher MD (OR = 1.41, 95%CI = 0.97-2.03; p = 0.070). For every 20% increase in relative caloric consumption the probability of having higher MD increased by 5% (OR = 1.05, 95%CI = 0.98-1.14; p = 0.178), not observing differences between the categories of explanatory variables. Caloric restriction was not associated with MD in our study. Conclusions: This is the first study exploring the association between MD and the effect of caloric deficit or excessive caloric consumption according to the energy requirements of each woman. Although caloric restriction does not seem to affect breast density, a caloric intake above predicted levels seems to increase this phenotypeThis study was supported by the Research Grant FIS PI060386 from Spanish Public Health Research Fund (Fondo de Investigacion Sanitaria); the Carlos III Institute of Health (Institute de Salud Carlos III)PI15CIII/0029 and PI15CIII/00013; the EPY 1306/06Collaboration Agreement between Astra-Zeneca and the Carlos III Institute of Health; and a grant from the Spanish Federation of Breast Cancer Patients (FECMA EPY 1169/10).Del Pozo, MDP.; Castelló, A.; Vidal, C.; Salas -Trejo, D.; Sanchez Contador, C.; Pedraz-Pingarrón, C.; Moreno, MP.... (2018). Overeating, caloric restriction and mammographic density in Spanish women. DDM-Spain study. Maturitas. 117:57-63. https://doi.org/10.1016/j.maturitas.2018.09.006S576311

Three-dimensional technology facilitates surgical performance of novice laparoscopy surgeons: a quantitative assessment on a porcine kidney model

Objective To determine whether the use of 3-dimensional (3D) imaging translates into a better surgical performance of naïve urologic laparoscopic surgeons during pyeloplasty (PY) and partial nephrectomy (PN) procedures. Materials and Methods Eighteen surgeons without any previous laparoscopic experience were randomly assigned to perform PY and PN in a porcine model using initially 2-dimensional (2D) and 3D laparoscopy. A surgical performance score was rated by an "expert" tutor through a modified 5-item global rating scale contemplating operative field view, bimanual dexterity, efficiency, tissue handling, and autonomy. Overall surgical time, complications, subjective perception of participating surgeons, and inconveniences related to the 3D vision were recorded. Results No difference in terms if operative time was found between 2D or 3D laparoscopy for both the PY (P =.51) and the PN (P =.28) procedures. A better rate in terms of surgical performance score was noted by the tutors when the study participants were using 3D vs 2D, for both PY (3.6 [0.8] vs 3.0 [0.4]; P =.034) and PN (3.6 [0.51] vs 3.15 [0.63]; P =.001). No complications occurred in any of the procedures. Most (77.2%) of the participating na??ve laparoscopic surgeons had the perception that 3D laparoscopy was overall easier than 2D. Headache (18.1%), nausea (18.1%), and visual disturbance (18.1%) were the most common issues reported by the surgeons during 3D procedures. Conclusion Despite the absence of translation in a shorter operative time, the use of 3D technology seems to facilitate the surgical performance of naive surgeons during laparoscopic kidney procedures on a porcine model

Impact of COVID-19 on medical education: Introducinghomo digitalis

Purpose To determine how members of the Societe Internationale d'Urologie (SIU) are continuing their education in the time of COVID-19. Methods A survey was disseminated amongst SIU members worldwide by email. Results were analyzed to examine the influence of age, practice region and settings on continuing medical education (CME) of the respondents. Results In total, 2494 respondents completed the survey. Internet searching was the most common method of CME (76%; allps = 2 platforms, with approximately 10% of the respondents using up to 5 different platforms. Urologists < 40 years old were more likely to use online literature (69%), podcasts/AV media (38%), online CME courses/webinars (40%), and social media (39%). There were regional variations in the CME modality used but no significant difference in the number of methods by region. There was no significant difference in responses between urologists in academic/public hospitals or private practice. Conclusion During COVID-19, urologists have used web-based learning for their CME. Internet learning and literature were the top frequently cited learning methods. Younger urologists are more likely to use all forms of digital learning methods, while older urologists prefer fewer methods

Preoperative Risk-Stratification of High-Risk Prostate Cancer: A Multicenter Analysis

Background: Cancer-specific survival (CSS) within high-risk non-metastatic prostate cancer varies dramatically. It is likely that within this heterogenous population there are subgroup(s) at extraordinary risk, burdened with an exaptational poor prognosis. Establishing the characteristics of these group(s) would have significant clinical implications since high quality preoperative risk stratification remains the cornerstone of therapeutic decision making to date. Objective: To stratify high-risk prostate cancer based on preoperative characteristics and evaluate cancer specific survival after radical prostatectomy. Method: The EMPaCT multi-center database offers an international population of non-metastatic high-risk prostate cancer. Preoperative characteristics such as age, biopsy Gleason score, PSA and clinical stage were subcategorized. A multivariate analysis was performed using predictors showing significant survival heterogeneity after stratification, as observed by a univariate analysis. Based upon the hazard ratios of this multivariate analysis, a proportional score system was created. The most ideal group distribution was evaluated trough different score cut-off's. The predictive value was tested by the herald C index. Results: An overall 5-years CSS of 94% was noted within the entire high-risk cohort (n = 4,879). Except for age, all preoperative risk factors showed a significantly differing CSS. Multivariate analysis indicated, T4 stage as being the strongest predictor of CSS (HR: 3.31), followed by ISUP grade 5 group (HR 3,05). A score system was created by doubling the hazard ratios of this multivariate analysis and rounding off to the nearest complete number. Multivariate analysis suggested 0, 4, 8, and 12 pts as being the most optimal group distribution (p-value: 0.0015). Five-years CSS of these groups were 97, 93, 87, and 70%, respectively. The calculated Herald C-index of the model was 0.77. Conclusion: An easy-to-use pre-operative model for risk stratification of newly diagnosed high-risk prostate cancer is presented. The heterogeneous CSS of high-risk non-metastatic prostate cancer after radical prostatectomy is illustrated. The model is clinically accessible through an online calculator, presenting cancer specific survival based on individualized patient characteristics