Imaging techniques for local recurrence of prostate cancer: For whom, why and how?

AbstractSince there are salvage solutions, it is important to detect local recurrence of prostate cancer as early as possible. The first sign is “biochemical failure” in that the prostate specific antigen (PSA) concentration rises again. The definition of biochemical failure varies depending on the initial treatment: PSA greater than 0.2ng/mL after prostatectomy, nadir+2ng/mL after radiotherapy. There is no standardised definition of biochemical failure after cryotherapy, focused ultrasound, or brachytherapy. Magnetic resonance imaging (MRI) (particularly dynamic MRI) can detect local recurrence with good sensitivity. The role of spectroscopy is still under discussion. For the moment, ultrasound techniques are less effective than MRI

Sumoylation of the THO complex regulates the biogenesis of a subset of mRNPs

International audienceAssembly of messenger ribonucleoparticles (mRNPs) is a pivotal step in gene expression, but only a few molecular mechanisms contributing to its regulation have been described. Here, through a comprehensive proteomic survey of mRNP assembly, we demonstrate that the SUMO pathway specifically controls the association of the THO complex with mRNPs. We further show that the THO complex, a key player in the interplay between gene expression, mRNA export and genetic stability, is sumoylated on its Hpr1 subunit and that this modification regulates its association with mRNPs. Altered recruitment of the THO complex onto mRNPs in sumoylation-defective mutants does not affect bulk mRNA export or genetic stability, but impairs the expression of acidic stress-induced genes and, consistently, compromises viability in acidic stress conditions. Importantly, inactivation of the nuclear exosome suppresses the phenotypes of the hpr1 non-sumoylatable mutant, showing that SUMO-dependent mRNP assembly is critical to allow a specific subset of mRNPs to escape degradation. This article thus provides the first example of a SUMO-dependent mRNP-assembly event allowing a refined tuning of gene expression, in particular under specific stress conditions

The probe beam linac in CTF3

JACoW web site http://accelconf.web.cern.ch/AccelConf/e06/The test facility CTF3, presently under construction at CERN within an international collaboration, is aimed at demonstrating the key feasibility issues of the multi-TeV linear collider CLIC. The objective of the probe beam linac is to "mimic" the main beam of CLIC in order to measure precisely the performances of the 30 GHz CLIC accelerating structures. In order to meet the required parameters of this 200 MeV probe beam, in terms of emittance, energy spread and bunch-length, the most advanced techniques have been considered: laser triggered photo-injector, velocity bunching, beam-loading compensation, RF pulse compression ... The final layout is described, and the selection criteria and the beam dynamics results are reviewed

What Is the Negative Predictive Value of Multiparametric Magnetic Resonance Imaging in Excluding Prostate Cancer at Biopsy? A Systematic Review and Meta-analysis from the European Association of Urology Prostate Cancer Guidelines Panel

Context: It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy. Objective: To systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicion of PCa. Evidence acquisition: The Embase, Medline, and Cochrane databases were searched up to February 2016. Studies reporting prebiopsy mpMRI results using transrectal or transperineal biopsy as a reference standard were included. We further selected for meta-analysis studies with at least 10-core biopsies as the reference standard, mpMRI comprising at least T2-weighted and diffusion-weighted imaging, positive mpMRI defined as a Prostate Imaging Reporting Data System/Likert score of ≥3/5 or ≥4/5, and results reported at patient level for the detection of overall PCa or clinically significant PCa (csPCa) defined as Gleason ≥7 cancer. Evidence synthesis: A total of 48 studies (9613 patients) were eligible for inclusion. At patient level, the median prevalence was 50.4% (interquartile range [IQR], 36.4–57.7%) for overall cancer and 32.9% (IQR, 28.1–37.2%) for csPCa. The median mpMRI NPV was 82.4% (IQR, 69.0–92.4%) for overall cancer and 88.1% (IQR, 85.7–92.3) for csPCa. NPV significantly decreased when cancer prevalence increased, for overall cancer (r = –0.64, p < 0.0001) and csPCa (r = –0.75, p = 0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. Seven reported results for overall PCa. When the overall PCa prevalence increased from 30% to 60%, the combined NPV estimates decreased from 88% (95% confidence interval [95% CI], 77–99%) to 67% (95% CI, 56–79%) for a cut-off score of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off score of ≥3/5 was 87.9%. Conclusions: The NPV of mpMRI varied greatly depending on study design, cancer prevalence, and definitions of positive mpMRI and csPCa. As cancer prevalence was highly variable among series, risk stratification of patients should be the initial step before considering prebiopsy mpMRI and defining those in whom biopsy may be omitted when the mpMRI is negative. Patient summary This systematic review examined if multiparametric magnetic resonance imaging (MRI) scan can be used to reliably predict the absence of prostate cancer in patients suspected of having prostate cancer, thereby avoiding a prostate biopsy. The results suggest that whilst it is a promising tool, it is not accurate enough to replace prostate biopsy in such patients, mainly because its accuracy is variable and influenced by the prostate cancer risk. However, its performance can be enhanced if there were more accurate ways of determining the risk of having prostate cancer. When such tools are available, it should be possible to use an MRI scan to avoid biopsy in patients at a low risk of prostate cancer

ESUR/ESUI consensus statements on multi-parametric MRI for the detection of clinically significant prostate cancer: quality requirements for image acquisition, interpretation and radiologists’ training

Objectives: This study aims to define consensus-based criteria for acquiring and reporting prostate MRI and establishing prerequisites for image quality. Methods: A total of 44 leading urologists and urogenital radiologists who are experts in prostate cancer imaging from the European Society of Urogenital Radiology (ESUR) and EAU Section of Urologic Imaging (ESUI) participated in a Delphi consensus process. Panellists completed two rounds of questionnaires with 55 items under three headings: image quality assessment, interpretation and reporting, and radiologists’ experience plus training centres. Of 55 questions, 31 were rated for agreement on a 9-point scale, and 24 were multiple-choice or open. For agreement items, there was consensus agreement with an agreement ≥ 70% (score 7–9) and disa

DNA protection by histone-like protein HU from the hyperthermophilic eubacterium Thermotoga maritima

In mesophilic prokaryotes, the DNA-binding protein HU participates in nucleoid organization as well as in regulation of DNA-dependent processes. Little is known about nucleoid organization in thermophilic eubacteria. We show here that HU from the hyperthermophilic eubacterium Thermotoga maritima HU bends DNA and constrains negative DNA supercoils in the presence of topoisomerase I. However, while binding to a single site occludes ∼35 bp, association of T. maritima HU with DNA of sufficient length to accommodate multiple protomers results in an apparent shorter occluded site size. Such complexes consist of ordered arrays of protomers, as revealed by the periodicity of DNase I cleavage. Association of TmHU with plasmid DNA yields a complex that is remarkably resistant to DNase I-mediated degradation. TmHU is the only member of this protein family capable of occluding a 35 bp nonspecific site in duplex DNA; we propose that this property allows TmHU to form exceedingly stable associations in which DNA flanking the kinks is sandwiched between adjacent proteins. We suggest that T. maritima HU serves an architectural function when associating with a single 35 bp site, but generates a very stable and compact aggregate at higher protein concentrations that organizes and protects the genomic DNA

ESUR/ESUI consensus statements on multi-parametric MRI for the detection of clinically significant prostate cancer: quality requirements for image acquisition, interpretation and radiologists’ training

Funder: Radboud University Medical CenterAbstract: Objectives: This study aims to define consensus-based criteria for acquiring and reporting prostate MRI and establishing prerequisites for image quality. Methods: A total of 44 leading urologists and urogenital radiologists who are experts in prostate cancer imaging from the European Society of Urogenital Radiology (ESUR) and EAU Section of Urologic Imaging (ESUI) participated in a Delphi consensus process. Panellists completed two rounds of questionnaires with 55 items under three headings: image quality assessment, interpretation and reporting, and radiologists’ experience plus training centres. Of 55 questions, 31 were rated for agreement on a 9-point scale, and 24 were multiple-choice or open. For agreement items, there was consensus agreement with an agreement ≥ 70% (score 7–9) and disagreement of ≤ 15% of the panellists. For the other questions, a consensus was considered with ≥ 50% of votes. Results: Twenty-four out of 31 of agreement items and 11/16 of other questions reached consensus. Agreement statements were (1) reporting of image quality should be performed and implemented into clinical practice; (2) for interpretation performance, radiologists should use self-performance tests with histopathology feedback, compare their interpretation with expert-reading and use external performance assessments; and (3) radiologists must attend theoretical and hands-on courses before interpreting prostate MRI. Limitations are that the results are expert opinions and not based on systematic reviews or meta-analyses. There was no consensus on outcomes statements of prostate MRI assessment as quality marker. Conclusions: An ESUR and ESUI expert panel showed high agreement (74%) on issues improving prostate MRI quality. Checking and reporting of image quality are mandatory. Prostate radiologists should attend theoretical and hands-on courses, followed by supervised education, and must perform regular performance assessments. Key Points: • Multi-parametric MRI in the diagnostic pathway of prostate cancer has a well-established upfront role in the recently updated European Association of Urology guideline and American Urological Association recommendations. • Suboptimal image acquisition and reporting at an individual level will result in clinicians losing confidence in the technique and returning to the (non-MRI) systematic biopsy pathway. Therefore, it is crucial to establish quality criteria for the acquisition and reporting of mpMRI. • To ensure high-quality prostate MRI, experts consider checking and reporting of image quality mandatory. Prostate radiologists must attend theoretical and hands-on courses, followed by supervised education, and must perform regular self- and external performance assessments