Pre-biopsy MRI as an adjunct for cancer detection in men with elevated PSA and no previous biopsy

The role of magnetic resonance imaging (MRI) prior to biopsy in the diagnosis of prostate cancer in biopsy-naïve patients has been strengthened by recent developments such as the PIRADS V2 criteria, which cover acquisition, interpretation, and reporting for clinical practice and data collection for research. Important questions on the role of prostate MRI remain: can MRI be used as a triage test before first biopsy series? Can it be used to avoid the use of systematic biopsies (SB) and instead use only targeted biopsies (TB) to MRI-suspicious lesions? Studies to evaluate image guided TB compared to SB have started to accumulate. Objectives of these studies should be to reduce the detection of clinically insignificant disease, to maximize the detection of clinically significant cancer (CSC), to better assess disease size, grade and location. Accurate diagnosis will allow the choice of the most appropriate treatments options, minimising side effects and reducing overtreatment. Study results on MRI-TB detection rates are promising however some limitations should be considered. The majority of published and ongoing studies have been performed at expert centres, in order to demonstrate the optimal performance of MRI. Then, the validation of this strategy in less specialised institutions will be necessary before incorporating recommendations in international guidelines. It necessitates training for radiologists and urologists to perform and read MRI and MRI-targeted biopsy through education programs and standardization tools. All these advances will be consolidated with expected genetic screening tools to improve the detection of aggressive cancer

A multicentre randomised controlled trial assessing whether MRI-targeted biopsy is non-inferior to standard transrectal ultrasound guided biopsy for the diagnosis of clinically significant prostate cancer in men without prior biopsy: a study protocol

INTRODUCTION: The classical pathway for the diagnosis of prostate cancer is transrectal ultrasound-guided (TRUS) biopsy of the prostate initiated on the basis of a raised prostate-specific antigen (PSA). An alternative pathway is to perform multi-parametricMRI (MPMRI) to localise cancer and to use this information to influence the decision for, and conduct of, a subsequent biopsy, known as an MPMRI-targeted biopsy. An MPMRI pathway has been shown to detect a similar or greater amount of clinically significant cancer as TRUS biopsy but has several advantages, including the potential to biopsy fewer men with fewer cores. METHODS: This is a pragmatic, international, multicentre, parallel group randomised study in which men are allocated in a 1:1 ratio to an MPMRI or TRUS biopsy pathway. This study will assess whether an MPMRI-targeted biopsy approach is non-inferior to a standard TRUS biopsy approach in the diagnosis of clinically significant cancer.Men in the MRI arm will undergo targeted biopsy of suspicious areas only and no biopsy will be carried out if the MRI is non-suspicious. Men in the TRUS biopsy will undergo a standard 10-12-core TRUS biopsy. The main inclusion criteria are a serum PSA ≤20 ng/mL, a digital rectal examination finding of T2 or less and no prior prostate biopsy.The primary outcome is the proportion of men with clinically significant cancer detected. A sample size of at least 470 patients is required. Key secondary outcomes include the proportion of clinically insignificant cancer detected. ETHICS AND DISSEMINATION: Ethical approval was obtained from the National Research Ethics Committee East Midlands, Leicester (15/EM/0188). Results of this study will be disseminated through national and international papers. The participants and relevant patient support groups will be informed about the results of the study. REGISTRATION DETAILS: NCT02380027; Pre-results

Low-risk prostate cancer selected for active surveillance with negative MRI at entry: can repeat biopsies at 1 year be avoided? A pilot study

Purpose: In patients considered for active surveillance (AS), the use of MRI and targeted biopsies (TB) at entry challenges the approach of routine “per protocol” repeat systematic biopsies (SB) at 1 year. This pilot study aimed to assess whether an approach of performing repeat biopsies only if PSA kinetics are abnormal would be safe and sufficient to detect progression. / Methods: Prospective single-centre study of 149 patients on AS with low-risk PCa, a negative MRI at entry, followed for a minimum of 12 months between 01/2007 and 12/2015. Group 1 (n = 78) patients had per-protocol 12-month repeat SB; group 2 (n = 71) patients did not. Surveillance tests for tumour progression were for both groups: for cause SB and MRI-TB biopsies if PSA velocity (PSA-V) > 0.75 ng/ml/year, or PSA doubling time (PSADT) < 3 years. The main objectives are to compare the 2-year rates of tumour progression and AS discontinuation between groups. The secondary objectives are to estimate the diagnostic power of PSA-V and PSA-DT, to predict the risk of tumour progression. / Results: Overall, 21 out of 149 patients (14.1%) showed tumour progression, 17.1% for group 1 and 12.3% for group 2, and 31 (21.2%) discontinued AS at 2 years. There was no difference between the 2 groups (p = 0.56). The area under the PSA-V and PSADT curves to predict tumour progression was 0.92 and 0.83, respectively. / Conclusions: We did not find any significant difference for progression and AS discontinuation rate between the 2 groups. The PSA kinetic seems accurate as a marker of tumour progression. These results support the conduct of a multi-centre prospective trial to confirm these findings

TOOKAD® Soluble focal therapy: pooled analysis of three phase II studies assessing the minimally invasive ablation of localized prostate cancer

Purpose: To evaluate the 6-month effects of the recommended drug and light dosage in focal vascular-targeted photodynamic therapy (VTP) using TOOKAD® Soluble in patients with localized prostate cancer (LPCa). Methods: We performed a pooled analysis of 117 men with LPCa, PSA <10 ng/mL, and Gleason score ≤7 (3 + 4), from 3 studies who received a 10-min intravenous infusion of a single dose of 4 mg/kg TOOKAD® Soluble, activated by a 753-nm light at 200 J/cm delivered in the prostate by transperineal fibres under transrectal ultrasound guidance. Primary endpoint was 6-month negative biopsies in the treated lobe(s). PSA was measured at month 1, 3, and 6. Magnetic resonance imaging was performed at day 7, month 3, and 6. International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) and adverse events were reported at day 7, month 1, 3, and 6. Results: Month 6 negative biopsy rate was 68.4 % in the overall evaluable population (N = 114) and 80.6 % for patients treated by hemiablation with light density index (LDI) ≥ 1 (N = 67). Mean prostate necroses at week-1 were 76.5 and 86.3 %, respectively. In both groups, PSA levels at month 6 decreased by 2.0 ng/mL. Small changes from baseline for IPSS and IIEF-5 indicated a slight improvement in urinary function and a slight deterioration in sexual function. Conclusions: Focal VTP treatment with TOOKAD® Soluble at 4 mg/kg and 200 J/cm resulted in a negative 6-month biopsy rate of 68.4 % for the whole population and 80.6 % for patients treated by hemiablation with LDI ≥ 1. The treatment was well tolerated. Two phase III studies will reach completion in early 2015

Natural Variability and Warming Signals in Global Ocean Wave Climates

地球全体の波浪特性の変化傾向と自然変動の関係を解明 --地球温暖化の沿岸域への影響を定量化--. 京都大学プレスリリース. 2021-06-15.This paper presents a multivariate classification of the global wave climate into types driven by atmospheric circulation patterns. The primary source of the net long-term variability is evaluated based on historical wave simulations. Results show that the monsoon, extratropical, subtropical, and polar wave climate types of the Pacific and North Atlantic Oceans are dominated by natural variability, whereas the extratropical and subtropical wave climate types in the Indian Ocean, and the tropical wave climate types of the Atlantic and Pacific Oceans exhibit a global warming signal. In the Pacific sector of the Southern Ocean, strong natural variability may mask a global warming signal that is yet to emerge as being statistically significant. In addition, wave climate teleconnections were found across the world that can provide a framework for joint strategies to achieve the goals of climate adaption for resilient coastal communities and environments

Determination of optimal drug dose and light dose index to achieve minimally invasive focal ablation of localised prostate cancer using WST11-vascular-targeted photodynamic (VTP) therapy

Objective: To determine the optimal drug and light dose for prostate ablation using WST11 (TOOKAD® Soluble) for vascular-targeted photodynamic (VTP) therapy in men with low-risk prostate cancer. Patients and Methods: In all, 42 men with low-risk prostate cancer were enrolled in the study but two who underwent anaesthesia for the procedure did not receive the drug or light dose. Thus, 40 men received a single dose of 2, 4 or 6 mg/kg WST11 activated by 200 J/cm light at 753 nm. WST11 was given as a 10-min intravenous infusion. The light dose was delivered using cylindrical diffusing fibres within hollow plastic needles positioned in the prostate using transrectal ultrasonography (TRUS) guidance and a brachytherapy template. Magnetic resonance imaging (MRI) was used to assess treatment effect at 7 days, with assessment of urinary function (International Prostate Symptom Score [IPSS]), sexual function (International Index of Erectile Function [IIEF]) and adverse events at 7 days, 1, 3 and 6 months after VTP. TRUS-guided biopsies were taken at 6 months. Results: In all, 39 of the 40 treated men completed the follow-up. The Day-7 MRI showed maximal treatment effect (95% of the planned treatment volume) in men who had a WST11 dose of 4 mg/kg, light dose of 200 J/cm and light density index (LDI) of >1. In the 12 men treated with these parameters, the negative biopsy rate was 10/12 (83%) at 6 months, compared with 10/26 (45%) for the men who had either a different drug dose (10 men) or an LDI of <1 (16). Transient urinary symptoms were seen in most of the men, with no significant difference in IPSS score between baseline and 6 months after VTP. IIEF scores were not significantly different between baseline and 6 months after VTP. Conclusion: Treatment with 4 mg/kg TOOKAD Soluble activated by 753 nm light at a dose of 200 J/cm and an LDI of >1 resulted in treatment effect in 95% of the planned treatment volume and a negative biopsy rate at 6 months of 10/12 men (83%)

Structure stability in the simple element sodium under pressure

The simple alkali metal Na, that crystallizes in a body-centred cubic structure at ambient pressure, exhibits a wealth of complex phases at extreme conditions as found by experimental studies. The analysis of the mechanism of stabilization of some of these phases, namely, the low-temperature Sm-type phase and the high-pressure cI16 and oP8 phases, shows that they satisfy the criteria for the Hume-Rothery mechanism. These phases appear to be stabilized due to a formation of numerous planes in a Brillouin-Jones zone in the vicinity of the Fermi sphere of Na, which leads to the reduction of the overall electronic energy. For the oP8 phase, this mechanism seems to be working if one assumes that Na becomes divalent metal at this density. The oP8 phase of Na is analysed in comparison with the MnP-type oP8 phases known in binary compounds, as well as in relation to the hP4 structure of the NiAs-type

A panel of kallikrein markers can predict outcome of prostate biopsy following clinical work-up: an independent validation study from the European Randomized Study of Prostate Cancer screening, France

<p>Abstract</p> <p>Background</p> <p>We have previously shown that a panel of kallikrein markers - total prostate-specific antigen (PSA), free PSA, intact PSA and human kallikrein-related peptidase 2 (hK2) - can predict the outcome of prostate biopsy in men with elevated PSA. Here we investigate the properties of our panel in men subject to clinical work-up before biopsy.</p> <p>Methods</p> <p>We applied a previously published predictive model based on the kallikrein panel to 262 men undergoing prostate biopsy following an elevated PSA (≥ 3 ng/ml) and further clinical work-up during the European Randomized Study of Prostate Cancer screening, France. The predictive accuracy of the model was compared to a "base" model of PSA, age and digital rectal exam (DRE).</p> <p>Results</p> <p>83 (32%) men had prostate cancer on biopsy of whom 45 (54%) had high grade disease (Gleason score 7 or higher). Our model had significantly higher accuracy than the base model in predicting cancer (area-under-the-curve [AUC] improved from 0.63 to 0.78) or high-grade cancer (AUC increased from 0.77 to 0.87). Using a decision rule to biopsy those with a 20% or higher risk of cancer from the model would reduce the number of biopsies by nearly half. For every 1000 men with elevated PSA and clinical indication for biopsy, the model would recommend against biopsy in 61 men with cancer, the majority (≈80%) of whom would have low stage <it>and </it>low grade disease at diagnosis.</p> <p>Conclusions</p> <p>In this independent validation study, the model was highly predictive of prostate cancer in men for whom the decision to biopsy is based on both elevated PSA and clinical work-up. Use of this model would reduce a large number of biopsies while missing few cancers.</p