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.
Targeted therapy against tumor angiogenesis is widely used in clinical practice for patients with colorectal liver metastases (CRLM). Possible predictive biomarkers for tumor angiogenesis, such as, ...microvessel density (MVD), hypoxia and cell proliferation, can be determined using immunohistochemical staining. However, patients ineligible for surgical treatment need to undergo invasive diagnostic interventions in order to determine these biomarkers. CT perfusion (CTP) is an emerging functional imaging technique, which can non-invasively determine vascular properties of solid tumors. The purpose of this study was to evaluate CTP with histological biomarkers in CRLM.
Patients with CRLM underwent CTP one day before liver surgery. CTP analysis was performed on the entire volume of the largest metastases in each patient. Dual-input maximum slope analysis was used and data concerning arterial flow (AF), portal flow (PF) and perfusion index (PI) were recorded. Immunohistochemical staining with CD34, M75/CA-IX and MIB-1 was performed on the rim in the midsection of the tumor to determine respectively MVD, hypoxia and cell proliferation.
Twenty CRLM in 20 patients were studied. Mean size of the largest CRLM was 37 mm (95% CI 21-54 mm). Mean AF and PF were respectively 64 ml/min/100ml (95% CI 48-79) and 30 ml/min/100ml (95% CI 22-38). Mean PI was 68% (95% CI 62-73). No significant correlation was found between tumor growth patterns and CTP (p = 0.95). MVD did not significantly correlate to AF (r = 0.05; p = 0.84), PF (r = 0.17; p = 0.47) and PI (r = -0.12; p = 0.63). Cell proliferation also did not significantly correlate to AF (r = 0.07; p = 0.78), PF (r = -0.01; p = 0.95) and PI (r = 0.15; p = 0.52). Hypoxia did not significantly correlate to AF (r = -0.05; p = 0.83), however, significantly to PF (r = 0.51; p = 0.02) and a trend to negative correlation with PF (r = -0.43; p = 0.06). However, after controlling the false discovery rate, no significant correlation between CTP and used immunohistochemical biomarkers was found.
In conclusion, this feasibility study found a trend to negative correlation between PI and hypoxia, CTP might therefore possibly evaluate this prognostic marker in CRLM non-invasively. However, CTP is not an appropriate technique for the assessment of microvessels or cell proliferation in CRLM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose We determined the positive and negative predictive values of multiparametric magnetic resonance imaging for extraprostatic extension at radical prostatectomy for different prostate cancer ...risk groups. Materials and Methods We evaluated a cohort of 183 patients who underwent 3 Tesla multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted magnetic resonance imaging and dynamic contrast enhanced sequences, with an endorectal coil before radical prostatectomy. Pathological stage at radical prostatectomy was used as standard reference for extraprostatic extension. The cohort was classified into low, intermediate and high risk groups according to the D’Amico criteria. We recorded prevalence of extraprostatic extension at radical prostatectomy and determined sensitivity, specificity, positive predictive value and negative predictive value of multiparametric magnetic resonance imaging for extraprostatic extension in each group. Univariate and multivariate analyses were performed to identify predictors of extraprostatic extension at radical prostatectomy. Results The overall prevalence of extraprostatic extension at radical prostatectomy was 49.7% ranging from 24.7% to 77.1% between low and high risk categories. Overall staging accuracy of multiparametric magnetic resonance imaging for extraprostatic extension was 73.8%, with sensitivity, specificity, positive predictive value and negative predictive value of 58.2%, 89.1%, 84.1% and 68.3%, respectively. Positive predictive value of multiparametric magnetic resonance imaging for extraprostatic extension was best in the high risk cohort with 88.8%. Negative predictive value was highest in the low risk cohort with 87.7%. With an odds ratio of 10.3 multiparametric magnetic resonance imaging is by far the best preoperative predictor of extraprostatic extension at radical prostatectomy. Conclusions For adequate patient counseling, knowledge of predictive values of multiparametric magnetic resonance imaging for extraprostatic extension is of utmost importance. High negative predictive value, important for decisions on nerve sparing strategies at radical prostatectomy, is only reached in low risk subjects.
Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has ...previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×10
/L to 186×10
/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified "pathogenic" or "likely pathogenic" variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia.
Abstract Background Multiparametric magnetic resonance imaging (mpMRI) may have a role in detecting clinically significant prostate cancer in men with raised serum prostate-specific antigen levels. ...Variations in technique and the interpretation of images have contributed to inconsistency in its reported performance characteristics. Objective Our aim was to make recommendations on a standardised method for the conduct, interpretation, and reporting of prostate mpMRI for prostate cancer detection and localisation. Design, setting, and participants A consensus meeting of 16 European prostate cancer experts was held that followed the UCLA-RAND Appropriateness Method and facilitated by an independent chair. Measurement Before the meeting, 520 items were scored for “appropriateness” by panel members, discussed face to face, and rescored. Results and limitations Agreement was reached in 67% of 260 items related to imaging sequence parameters. T2-weighted, dynamic contrast-enhanced, and diffusion-weighted MRI were the key sequences incorporated into the minimum requirements. Consensus was also reached on 54% of 260 items related to image interpretation and reporting, including features of malignancy on individual sequences. A 5-point scale was agreed on for communicating the probability of malignancy, with a minimum of 16 prostatic regions of interest, to include a pictorial representation of suspicious foci. Limitations relate to consensus methodology. Dominant personalities are known to affect the opinions of the group and were countered by a neutral chairperson. Conclusions Consensus was reached on a number of areas related to the conduct, interpretation, and reporting of mpMRI for the detection, localisation, and characterisation of prostate cancer. Before optimal dissemination of this technology, these outcomes will require formal validation in prospective trials.
The goal of this study was to compare performance parameters of a single-use syringe and a multi-use MR contrast injector. We compared preparation time, cost for disposables and volumes of contrast ...material used for a single-use (SI) and a multi-use (MI) MR contrast injector in a prospective cross-over trial. During the first study period all consecutive patients eligible for dynamic MR on two systems were included during a period of 20 working days. After 10 days, the injector was switched. Radiographer satisfaction was evaluated using a questionnaire. Contrast usage and waste on system MI was optimised by extra instructions for our radiographers and measured during the second study period of 10 consecutive working days. A total of 202 and 163 patients for systems SI and MI were included, respectively. Average preparation time was 4:55 min for SI and 2:24 min for MI (p < 0.05). Contrast waste for SI was 13% using 7.5 ml syringes. Contrast waste for MI was 5% for 7.5 ml containers. Costs for disposables were lower for MI if more than 5 patients per day were injected. Radiographer satisfaction was higher for MI (4.7 versus 2.8 on a 5-point scale; p < 0.05). The multi-use MR contrast injector led to higher radiographer satisfaction, shorter preparation time, and lower cost if more than 5 patients were injected per day. In addition, cheaper contrast containers of 15 or 30 ml could be used for the first patients if more than 2 or more than 4 injections are performed per day, potentially leading to lower contrast waste.
Tumor ablation technologies, such as radiofrequency-, cryo- or high-intensity focused ultrasound (HIFU) ablation will destroy tumor tissue in a minimally invasive manner. Ablation generates large ...volumes of tumor debris in situ, releasing multiple bio-molecules like tumor antigens and damage-associated molecular patterns. To initiate an adaptive antitumor immune response, antigen-presenting cells need to take up tumor antigens and, following activation, present them to immune effector cells. The impact of the type of tumor ablation on the precise nature, availability and suitability of the tumor debris for immune response induction, however, is poorly understood. In this review, we focus on immune effects after HIFU-mediated ablation and compare these to findings using other ablation technologies. HIFU can be used both for thermal and mechanical destruction of tissue, inducing coagulative necrosis or subcellular fragmentation, respectively. Preclinical and clinical results of HIFU tumor ablation show increased infiltration and activation of CD4
+
and CD8
+
T cells. As previously observed for other types of tumor ablation technologies, however, this ablation-induced enhanced infiltration alone appears insufficient to generate consistent protective antitumor immunity. Therapies combining ablation with immune stimulation are therefore expected to be key to boost HIFU-induced immune effects and to achieve systemic, long-lasting, antitumor immunity.
The purpose of this diagnostic meta-analysis was to determine the diagnostic accuracy of multiparametric MRI for prostate cancer detection using anatomic T2-weighted imaging combined with two ...functional techniques: diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI).
We searched electronic databases, including MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 3, 2012. We included diagnostic accuracy studies using a combination of T2-weighted imaging, DWI, and DCE-MRI to detect prostate cancer with histopathologic data from prostatectomy or biopsy as the reference standard. The methodologic quality was assessed with version 2 of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool by two independent reviewers. Sensitivity and specificity of all studies were calculated from 2 × 2 tables, and the results were plotted in a hierarchic summary receiver operating characteristic plot.
Seven studies that met the inclusion criteria (526 patients) could be analyzed. The pooled data showed a specificity of 0.88 (95% CI, 0.82-0.92) and sensitivity of 0.74 (95% CI, 0.66-0.81) for prostate cancer detection, with negative predictive values (NPVs) ranging from 0.65 to 0.94. Subgroup analyses showed no significant difference between the subgroups.
The high specificity with variable but high NPVs and sensitivities implies a potential role for multiparametric MRI in detecting prostate cancer.
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