Imaging modalities in synchronous oligometastatic prostate cancer

Purpose Along with a number of other malignancies, the term "oligometastatic" prostate cancer has recently emerged. It represents an attempt to define a subtype of cancer with a limited metastatic load that might perform more favorably than a distinctly disseminated disease, or even one that may be managed in a potentially curative way. Since there is currently a knowledge gap of what imaging modalities should be utilized to classify patients as having this type of tumor, we aimed to shed light on the role of conventional and marker-based imaging in the setting of synchronous oligometastatic prostate cancer as well as summarize the available evidence for its clinical application. Methods A literature search on December 15th 2017 was conducted using the Pubmed database. Results Functional imaging techniques like Ga-68 PSMA. Ga-68 PSMA PET-CT has currently been shown the best detection rates for the assessment of nodal, bone and visceral metastases, especially for smaller lesions at low PSA levels. Conclusions Functional imaging helps detect low-burden disease metastatic patients. However, these imaging modalities are not available in every center and thus clinicians may be prone to prescribe systemic treatment rather than referring patients for cytoreductive treatments. We hope that the ongoing prospective trials will help guide clinicians in making a more personalized management of synchronous metastatic patients

Role of multiparametric magnetic resonance imaging in early detection of prostate cancer.

UNLABELLED: Most prostate cancers (PC) are currently found on the basis of an elevated PSA, although this biomarker has only moderate accuracy. Histological confirmation is traditionally obtained by random transrectal ultrasound guided biopsy, but this approach may underestimate PC. It is generally accepted that a clinically significant PC requires treatment, but in case of an non-significant PC, deferment of treatment and inclusion in an active surveillance program is a valid option. The implementation of multiparametric magnetic resonance imaging (mpMRI) into a screening program may reduce the risk of overdetection of non-significant PC and improve the early detection of clinically significant PC. A mpMRI consists of T2-weighted images supplemented with diffusion-weighted imaging, dynamic contrast enhanced imaging, and/or magnetic resonance spectroscopic imaging and is preferably performed and reported according to the uniform quality standards of the Prostate Imaging Reporting and Data System (PIRADS). International guidelines currently recommend mpMRI in patients with persistently rising PSA and previous negative biopsies, but mpMRI may also be used before first biopsy to improve the biopsy yield by targeting suspicious lesions or to assist in the selection of low-risk patients in whom consideration could be given for surveillance. TEACHING POINTS: ? MpMRI may be used to detect or exclude significant prostate cancer. ? MpMRI can guide targeted rebiopsy in patients with previous negative biopsies. ? In patients with negative mpMRI consideration could be given for surveillance. ? MpMRI may add valuable information for the optimal treatment selection

The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells

BACKGROUND: Neuroendocrine (NE) differentiation represents a common feature of prostate cancer and is associated with accelerated disease progression and poor clinical outcome. Nowadays, there is no treatment for this aggressive form of prostate cancer. The aim of this study was to determine the influence of the cannabinoid WIN 55,212-2 (WIN, a non-selective cannabinoid CB1 and CB2 receptor agonist) on the NE differentiation of prostate cancer cells.METHODS: NE differentiation of prostate cancer LNCaP cells was induced by serum deprivation or by incubation with interleukin-6, for 6 days. Levels of NE markers and signaling proteins were determined by western blotting. Levels of cannabinoid receptors were determined by quantitative PCR. The involvement of signaling cascades was investigated by pharmacological inhibition and small interfering RNA.RESULTS: The differentiated LNCaP cells exhibited neurite outgrowth, and increased the expression of the typical NE markers neuron-specific enolase and βIII tubulin (βIII Tub). Treatment with 3 μM WIN inhibited NK differentiation of LNCaP cells. The cannabinoid WIN downregulated the PI3K/Akt/mTOR signaling pathway, resulting in NE differentiation inhibition. In addition, an activation of AMP-activated protein kinase (AMPK) was observed in WIN-treated cells, which correlated with a decrease in the NE markers expression. Our results also show that during NE differentiation the expression of cannabinoid receptors CB1 and CB2 dramatically decreases.CONCLUSIONS: Taken together, we demonstrate that PI3K/Akt/AMPK might be an important axis modulating NE differentiation of prostate cancer that is blocked by the cannabinoid WIN, pointing to a therapeutic potential of cannabinoids against NE prostate cancer.Prostate Cancer and Prostatic Diseases advance online publication, 21 June 2016; doi:10.1038/pcan.2016.19.</p

Convective-scale perturbation growth across the spectrum of convective regimes

Convection-permitting ensembles have led to improved forecasts of many atmospheric phenomena. However, to fully utilize these forecasts the dependence of predictability on synoptic conditions needs to be understood. In this study, convective regimes are diagnosed based on a convective timescale which identifies the degree to which convection is in equilibrium with the large-scale forcing. Six convective cases are examined in a convection-permitting ensemble constructed using the Met Office Unified Model. The ensemble members were generated using small-amplitude buoyancy perturbations added into the boundary layer, which can be considered to represent turbulent fluctuations close to the gridscale. Perturbation growth is shown to occur on different scales with an order of magnitude difference between the regimes (O(1 km) for cases closer to non-equilibrium convection and O(10 km) for cases closer to equilibrium convection). This difference reflects the fact that cell locations are essentially random in the equilibrium events after the first 12 h of the forecast, indicating a more rapid upscale perturbation growth compared to the non-equilibrium events. Furthermore, large temporal variability is exhibited in all perturbation growth diagnostics for the nonequilibrium regime. Two boundary condition driven cases are also considered and show similar characteristics to the non-equilibrium cases, implying that caution is needed to interpret the timescale when initiation is not within the domain. Further understanding of perturbation growth within the different regimes could lead to a better understanding of where ensemble design improvements can be made beyond increasing the model resolution and could improve interpretation of forecasts

Elektrokemijski postupak za proizvodnju titanovih kompozitnih slitina

The paper presents a new method for precursors’ synthesis of titanium alloys matrix composites through an electrochemical process in molten calcium chloride. The cathode of the cell was made from metallic oxides powders and reinforcement ceramic particles, which were pressed and sintered into disk form and the anode from graphite. The process occurred at 850 °C, in two stages, at 2,7 / 3,2 V: the ionization of the oxygen in oxides and the reduction with calcium formed by electrolysis of calcium oxide fed in the electrolyte. The obtained composite precursors, in a form of metallic sponge, were consolidated by pressing and sintering. Chemical and structural analyses on composites samples were performed.Članak prikazuje novu metodu prethodne sinteze titanovih kompozitnih slitina s elektrokemijskim postupkom u rastaljenom kalcijevom kloridu. Katoda ćelije ustrojena je od praškastog metalnog oksida ojačan keramičkim česticama, koji je stlačen u obliku diska, a anoda je od grafita. Postupak se odvijao na 850 °C u dva stupnja, 2,7/3,2 V: ionizacija kisika u oksidima i redukcija kalcijem nastajala je elektrolizom kalcijevih oksida u elektrolitu. Dobiveni prethodno kompozit u obliku metalne spužve je očvrsnut tlačenjem i sinteriranjem. Provedena je kemijska i strukturna analiza uzoraka kompozita

Maternal VDR variants rather than 25-hydroxyvitamin D concentration during early pregnancy are associated with type 1 diabetes in the offspring

This study was supported by the Finnish Academy (grant 127219), the European Foundation for the Study of Diabetes, the Novo Nordisk Foundation, the Diabetes Research Foundation, the EVO funding of the South Ostrobothnia Central Hospital from the Ministry ofHealthand SocialAffairs (EVO1107), the BiomedicumHelsinki Foun- dation, the Jalmari and Rauha Ahokas Foundation, the Yrjö Jahnsson Foundation, the Suoma Loimaranta-Airila Fund, the Onni and Hilja Tuovinen Foundation and the Juho Vainio Foundation

Iodine and thyroid status during pregnancy and risk of stillbirth : A population-based nested case–control study

AbstractPrior research suggests that severe iodine deficiency in pregnancy may be associated with stillbirth. However, the relationship between mild to moderate iodine insufficiency, which is prevalent even in developed countries, and risk of stillbirth is unclear. We thus examined associations of iodine status and risk of stillbirth in a prospective population-based nested case–control study in Finland, a mild to moderately iodine insufficient population. Stillbirth cases (n = 199) and unaffected controls (n = 249) were randomly selected from among all singleton births in Finland from 2012 to 2013. Serum samples were collected between 10 and 14 weeks gestation and analysed for iodide, thyroglobulin (Tg) and thyroid-stimulating hormone (TSH). Odds ratios (ORs) and 95% confidence intervals (CIs) for stillbirth were estimated using logistic regression. After adjusting for maternal age, prepregnancy body mass index, socio-economic status and other factors, neither high nor low serum iodide was associated with risk of stillbirth (Q1 vs. Q2–Q3 OR = 0.92, 95% CI = 0.78–1.09; Q4 vs. Q2–Q3 OR = 0.78; 95% CI = 0.45–1.33). Tg and TSH were also not associated with risk of stillbirth in adjusted models. Maternal iodine status was not associated with stillbirth risk in this mildly to moderately iodine-deficient population. Tg and TSH, which reflect functional iodine status, were also not associated with stillbirth risk. The lack of associations observed between serum iodide, TSH and Tg and risk of stillbirth is reassuring, given that iodine deficiency in pregnancy is prevalent in developed countries.Abstract Prior research suggests that severe iodine deficiency in pregnancy may be associated with stillbirth. However, the relationship between mild to moderate iodine insufficiency, which is prevalent even in developed countries, and risk of stillbirth is unclear. We thus examined associations of iodine status and risk of stillbirth in a prospective population-based nested case–control study in Finland, a mild to moderately iodine insufficient population. Stillbirth cases (n = 199) and unaffected controls (n = 249) were randomly selected from among all singleton births in Finland from 2012 to 2013. Serum samples were collected between 10 and 14 weeks gestation and analysed for iodide, thyroglobulin (Tg) and thyroid-stimulating hormone (TSH). Odds ratios (ORs) and 95% confidence intervals (CIs) for stillbirth were estimated using logistic regression. After adjusting for maternal age, prepregnancy body mass index, socio-economic status and other factors, neither high nor low serum iodide was associated with risk of stillbirth (Q1 vs. Q2–Q3 OR = 0.92, 95% CI = 0.78–1.09; Q4 vs. Q2–Q3 OR = 0.78; 95% CI = 0.45–1.33). Tg and TSH were also not associated with risk of stillbirth in adjusted models. Maternal iodine status was not associated with stillbirth risk in this mildly to moderately iodine-deficient population. Tg and TSH, which reflect functional iodine status, were also not associated with stillbirth risk. The lack of associations observed between serum iodide, TSH and Tg and risk of stillbirth is reassuring, given that iodine deficiency in pregnancy is prevalent in developed countries

First comparison of retroperitoneal versus transperitoneal robot-assisted nephroureterectomy with bladder cuff : a single center study

Introduction. After recent presentation of the first complete robot-assisted retroperitoneal nephroureterectomy with bladder cuff (RRNU) for patients with upper tract urothelial cancer (UTUC), we aimed to compare this new surgical technique with robot-assisted transperitoneal nephroureter ectomy (TRNU) representing the current standard of care. Methods. Robot-assisted nephroureterectomies (NUs) were retrospectively analyzed and compared based on two groups: transperitoneal versus retroperitoneal approach. Baseline data were collected for patient demographics, tumor characteristics, intra- (EAUiaiC) and postoperative (Clavien-Dindo) complications, and perioperative variables. Tumor characteristics included grade of malignancy, clinical stage, and surgical margin status. Short-term follow-up data including 30-day readmission rates were collected. Statistical analyses were performed assuming a significant p-value of < 0.05. Results. The analysis includes perioperative patient data after proven UTUC of 24 TRNU versus 12 RRNU (mean age: 70 versus 71 years; BMI: 25.9 versus 26.1 kg/m 2 ; CCI score ≥ 4: 83% versus 75%; ASA score ≥ 3: 37% vs 33%). Intraoperative (16.4% vs 0%, p = 0.35) and postoperative (25% vs 12.5%, p = 0.64) complications demonstrated no significant discrepancy. Notably, RRNU demonstrated significantly shorter surgery time (p < 0.05) and length of stay (p < 0.05). There was no significant difference in histopathological tumor characteristics, whereas significantly more lymph nodes were removed through RRNU (11.0±3.3 vs. 6.4±5.1, p < 0.05). Finally, no statistical difference was shown in short-term follow-up. Conclusion. We report the first head-to-head comparison between RRNU and TRNU. RRNU proves to be a safe and feasible approach which appears to be non-inferior to TRNU. RRNU expands the spectrum of minimally invasive treatment options, particularly for patients with major previous abdominal surgery