Purpose
To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT).
Methods
An international ...collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results.
Results
mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers.
Conclusions
The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological community.
Aim
To evaluate the effects of the primary human bile acid, chenodeoxycholic acid (CDCA), and the bile acid sequestrant (BAS) colesevelam, instilled into the stomach, on plasma levels of ...glucagon‐like peptide‐1 (GLP‐1), glucose‐dependent insulinotropic polypeptide, glucose, insulin, C‐peptide, glucagon, cholecystokinin and gastrin, as well as on gastric emptying, gallbladder volume, appetite and food intake.
Methods
On four separate days, nine patients with type 2 diabetes, and 10 matched healthy control subjects received bolus instillations of (i) CDCA, (ii) colesevelam, (iii) CDCA + colesevelam or (iv) placebo. At baseline and for 180 min after instillation, blood was sampled.
Results
In both the type 2 diabetes group and the healthy control group, CDCA elicited an increase in GLP‐1 levels compared with colesevelam, CDCA + colesevelam and placebo, respectively (p < 0.05). The interventions did not affect plasma glucose, insulin or C‐peptide concentrations in any of the groups. CDCA elicited a small increase in plasma insulin : glucose ratio compared with colesevelam, CDCA + colesevelam and placebo in both groups. Compared with colesevelam, CDCA + colesevelam and placebo, respectively, CDCA increased glucagon and delayed gastric emptying in both groups.
Conclusions
CDCA increased GLP‐1 and glucagon secretion, and delayed gastric emptying. We speculate that bile acid‐induced activation of TGR5 on L cells increases GLP‐1 secretion, which, in turn, may result in amplification of glucose‐stimulated insulin secretion. Furthermore our data suggest that colesevelam does not have an acute effect on GLP‐1 secretion in humans.
Noninvasive fetal aneuploidy detection by use of free DNA from maternal plasma has recently been shown to be achievable by whole genome shotgun sequencing. The high-throughput next-generation ...sequencing platforms previously tested use a PCR step during sample preparation, which results in amplification bias in GC-rich areas of the human genome. To eliminate this bias, and thereby experimental noise, we have used single molecule sequencing as an alternative method.
For noninvasive trisomy 21 detection, we performed single molecule sequencing on the Helicos platform using free DNA isolated from maternal plasma from 9 weeks of gestation onwards. Relative sequence tag density ratios were calculated and results were directly compared to the previously described Illumina GAII platform.
Sequence data generated without an amplification step show no GC bias. Therefore, with the use of single molecule sequencing all trisomy 21 fetuses could be distinguished more clearly from euploid fetuses.
This study shows for the first time that single molecule sequencing is an attractive and easy to use alternative for reliable noninvasive fetal aneuploidy detection in diagnostics. With this approach, previously described experimental noise associated with PCR amplification, such as GC bias, can be overcome.
Fetal megacystis: a lot more than LUTO Fontanella, F.; Maggio, L.; Verheij, J. B. G. M. ...
Ultrasound in obstetrics & gynecology,
June 2019, 2019-Jun, 2019-06-00, 20190601, Letnik:
53, Številka:
6
Journal Article
Current surgical and ablative treatment options for prostate cancer (PCa) may result in a high incidence of (temporary) incontinence, erectile dysfunction and/or bowel damage. These side effects are ...due to procedure related effects on adjacent structures including blood vessels, bowel, urethra and/or neurovascular bundle. Ablation with irreversible electroporation (IRE) has shown to be effective and safe in destroying PCa cells and also has the potential advantage of sparing surrounding tissue and vital structures, resulting in less impaired functional outcomes and maintaining men's quality of life.
In this randomized controlled trial (RCT) on IRE in localized PCa, 200 patients with organ-confined, unilateral (T1c-T2b) low- to intermediate-risk PCa (Gleason sum score 6 and 7) on transperineal template-mapping biopsies (TTMB) will be included. Patients will be randomized into focal or extended ablation of cancer foci with IRE. Oncological efficacy will be determined by multiparametric Magnetic Resonance Imaging, Contrast-Enhanced Ultrasound imaging if available, TTMP and Prostate Specific Antigen (PSA) follow-up. Patients will be evaluated up to 5 years on functional outcomes and quality of life with the use of standardized questionnaires.
There is critical need of larger, standardized RCTs evaluating long-term oncological and functional outcomes before introducing IRE and other focal therapy modalities as an accepted and safe therapeutic option for PCa. This RCT will provide important short- and long-term data and elucidates the differences between focal or extended ablation of localized, unilateral low- to intermediate-risk PCa with IRE.
Clinicaltrials.gov database registration number NCT01835977. The Dutch Central Committee on Research Involving Human Subjects registration number NL50791.018.14.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To assess whether a diagnostic pathway in which prostate‐specific membrane antigen (PSMA) positron‐emission tomography (PET)/computed tomography (CT) is used as a single imaging modality is ...feasible to guide targeted biopsy and to detect clinically significant prostate cancer (csPCa) in biopsy‐naïve men at high‐risk of disease.
Patients and Methods
A total of 60 men with a prostate‐specific antigen (PSA) level of 20–50 ng/mL underwent 18F‐PSMA(DCFPyL)‐PET/CT prior to prostate biopsies in this prospective, non‐randomised cohort study. Magnetic resonance imaging (MRI) was not performed. Using a 12‐segment mapping model of the prostate, PSMA‐guided targeted biopsy was performed along with systematic biopsies. The detection rate of PCa and csPCa was assessed for combined systematic and targeted biopsy, and for targeted biopsy only. csPCa was defined as a prostate biopsy with an International Society of Uropathology (ISUP) Grade Group ≥2.
Results
Lesions suspicious for PCa in the prostate gland were observed on all PSMA‐PET/CTs. A total of 27/60 men (45%) already had metastatic disease on staging 18F‐PSMA(DCFPyL)‐PET/CT. Combined PSMA‐guided targeted and systematic biopsies detected PCa in 56/60 (93.3%) patients, with 52 of them (92.9%) having csPCa. PSMA‐guided targeted biopsy, if performed as a single biopsy modality, identified PCa in 52/60 men (86.7%) and in 27/27 men (100%) men with metastases.
Conclusions
Using the PSMA‐driven single imaging modality pathway in biopsy‐naïve men at high‐risk of PCa, a substantial number of diagnostic MRI scans could be avoided while at the same time obtaining adequate targeting, staging, and detection of csPCa.
The current standard for Prostate Cancer (PCa) detection in biopsy-naïve men consists of 10-12 systematic biopsies under ultrasound guidance. This approach leads to underdiagnosis and undergrading of ...significant PCa while insignificant PCa may be overdiagnosed. The recent developments in MRI and Contrast Enhanced Ultrasound (CEUS) imaging have sparked an increasing interest in PCa imaging with the ultimate goal of replacing these "blind" systematic biopsies with reliable imaging-based targeted biopsies.
In this trial, we evaluate and compare the PCa detection rates of multiparametric (mp)MRI-targeted biopsies, CEUS-targeted biopsies and systematic biopsies under ultrasound guidance in the same patients. After informed consent, 299 biopsy-naïve men will undergo mpMRI scanning and CEUS imaging 1 week prior to the prostate biopsy procedure. During the biopsy procedure, a systematic transrectal 12-core biopsy will be performed by one operator blinded for the imaging results and targeted biopsy procedure. Subsequently a maximum of 4 CEUS-targeted biopsies and/or 4 mpMRI-targeted biopsies of predefined locations determined by an expert CEUS reader using quantification techniques and an expert radiologist, respectively, will be taken by a second operator using an MRI-US fusion device. The primary outcome is the detection rate of PCa (all grades) and clinically significant PCa (defined as Gleason score ≥7) compared between the three biopsy protocols.
This trial compares the detection rate of (clinically significant) PCa, between both traditional systematic biopsies and targeted biopsies based on predefined regions of interest identified by two promising imaging technologies. It follows published recommendations on study design for the evaluation of imaging guided prostate biopsy techniques, minimizing bias and allowing data pooling. It is the first trial to combine mpMRI imaging and advanced CEUS imaging with quantification.
The Dutch Central Committee on Research Involving Human Subjects registration number NL52851.018.15, registered on 3 Nov 2015. Clinicaltrials.gov database registration number NCT02831920 , retrospectively registered on 5 July 2016.
Whole-gland extirpation or irradiation is considered the gold standard for curative oncological treatment for localized prostate cancer, but is often associated with sexual and urinary impairment ...that adversely affects quality of life. This has led to increased interest in developing therapies with effective cancer control but less morbidity. We aimed to provide details of physician consensus on patient selection for prostate focal therapy (FT) in the era of contemporary prostate cancer management.
We undertook a four-stage Delphi consensus project among a panel of 47 international experts in prostate FT. Data on three main domains (role of biopsy/imaging, disease and patient factors) were collected in three iterative rounds of online questionnaires and feedback. Consensus was defined as agreement in ⩾80% of physicians. Finally, an in-person meeting was attended by a core group of 16 experts to review the data and formulate the consensus statement.
Consensus was obtained in 16 of 18 subdomains. Multiparametric magnetic resonance imaging (mpMRI) is a standard imaging tool for patient selection for FT. In the presence of an mpMRI-suspicious lesion, histological confirmation is necessary prior to FT. In addition, systematic biopsy remains necessary to assess mpMRI-negative areas. However, adequate criteria for systematic biopsy remains indeterminate. FT can be recommended in D'Amico low-/intermediate-risk cancer including Gleason 4+3. Gleason 3+4 cancer, where localized, discrete and of favorable size represents the ideal case for FT. Tumor foci <1.5 ml on mpMRI or <20% of the prostate are suitable for FT, or up to 3 ml or 25% if localized to one hemi-gland. Gleason 3+3 at one core 1mm is acceptable in the untreated area. Preservation of sexual function is an important goal, but lack of erectile function should not exclude a patient from FT.
This consensus provides a contemporary insight into expert opinion of patient selection for FT of clinically localized prostate cancer.
Cross-linking mass spectrometry (MS) has substantially matured as a method over the past 2 decades through parallel development in multiple labs, demonstrating its applicability to protein structure ...determination, conformation analysis, and mapping protein interactions in complex mixtures. Cross-linking MS has become a much-appreciated and routinely applied tool, especially in structural biology. Therefore, it is timely that the community commits to the development of methodological and reporting standards. This white paper builds on an open process comprising a number of events at community conferences since 2015 and identifies aspects of Cross-linking MS for which guidelines should be developed as part of a Cross-linking MS standards initiative.
Leitner et al. propose steps toward the development of best practices in Cross-linking mass spectrometry in this white paper. This community-driven effort represents a consensus of approximately 30 groups from academia and industry and, if successfully implemented, will increase transparency and facilitate data reuse.
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