Multiparametric Prostate Magnetic Resonance Imaging and Cognitively Targeted Transperineal Biopsy in Patients With Previous Abdominoperineal Resection and Suspicion of Prostate Cancer.

OBJECTIVE: To report our experience with a combination of prostate magnetic resonance imaging (MRI) and transperineal ultrasound biopsy for evaluating the prostate in patients with elevated prostate-specific antigen (PSA) who have previously undergone abdominoperineal resection (APR). PATIENTS AND METHODS: We reviewed the records of 11 patients with a history of APR and clinical suspicion of prostate cancer due to elevated PSA levels over a 5-year period. All patients underwent multiparametric MRI at our institution prior to biopsy. MR diagnoses were validated either by transperineal ultrasound biopsy (Likert 3-5) guided by visual registration or clinical follow-up >6 months (Likert 1-2). RESULTS: All 7 cases with highly suspicious lesions (Likert 4-5) on MRI demonstrated cancer-1 case of Gleason 3 + 3 and 6 cases of Gleason ≥3 + 4 disease. Two cases with Likert 3 MR lesions revealed benign tissue upon biopsy. Two patients with no suspicious lesions on MRI were followed-up clinically, with PSA levels remaining stable over a mean period of 17.5 months (range 7-28 months). CONCLUSION: The use of prebiopsy multiparametric prostate MRI and subsequent cognitively targeted transperineal biopsy guided by visual registration can aid in the diagnostic pathway of patients with APR and a suspicion of prostate cancer.Author 1 has received a research grant from RWTH Aachen University Hospital (Aachen, Germany). Author 6 acknowledges support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.urology.2016.04.03

A head-to-head comparison of the inter- and intraobserver agreement of COVID-RADS and CO-RADS grading systems in a population with high estimated prevalence of COVID-19

Purpose To evaluate the inter- and intraobserver agreement of COVID-RADS and CO-RADS reporting systems among differently experienced radiologists in a population with high estimated prevalence of COVID-19. Materials and Methods Chest CT scans of patients with clinically-epidemiologically diagnosed COVID-19 were retrieved from an open-source MosMedData dataset, randomised, and independently assigned COVID-RADS and CO-RADS grades by an abdominal radiology fellow, thoracic imaging fellow and a consultant cardiothoracic radiologist. The inter- and intraobserver agreement of the two systems were assessed using the Fleiss’ and Cohen’s kappa coefficients, respectively. Results A total of 200 studies were included in the analysis. Both systems demonstrated moderate interobserver agreement, with kappa values of 0.51 (95% CI: 0.46-0.56) and 0.55 (95% CI: 0.50-0.59) for COVID-RADS and CO-RADS, respectively. When COVID-RADS and CO-RADS grades were dichotomised at cut-off values of 2B and 4 to evaluate the agreement between grades representing different levels of clinical suspicion for COVID-19, the interobserver agreement became substantial with kappa values of 0.74 (95% CI: 0.66-0.82) for COVID-RADS and 0.73 (95% CI: 0.65-0.81) for CO-RADS. The median intraobserver agreement was considerably higher for CO-RADS reaching 0.81 (95% CI: 0.43-0.76) compared with 0.60 (95% CI: 0.43-0.76) of COVID-RADS. Conclusions COVID-RADS and CO-RADS showed comparable interobserver agreement, which was moderate when grades were compared head-to-head and substantial when grades were dichotomised to better reflect the underlying levels of suspicion for COVID-19. The median intraobserver agreement of CO-RADS was, however, considerably higher compared with COVID-RADS. Advances in knowledge This paper provides a comprehensive review of the newly introduced COVID-19 chest CT reporting systems, which will help radiologists of all sub-specialties and experience levels make an informed decision on which system to use in their own practice.Acknowledgments: The authors acknowledge support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre

Lesion Targeted CT-Guided Transgluteal Prostate Biopsy in Combination With Prebiopsy MRI in Patients Without Rectal Access.

With prostate and colorectal malignancies being the most common cancers in men, elevated prostate specific antigen (PSA) in patients without rectal access due to prior surgery poses a diagnostic dilemma. We report the first use of CT-guided biopsy in combination with prebiopsy MRI in 2 patients with a clinical suspicion of prostate cancer and no rectal access. In both cases, a diagnostic multiparametric MRI of the prostate was performed to detect and to localize a potential suspicious lesion. The localization served as a cognitive map for guiding needle placement using a CT-guided transgluteal approach

Using a Recurrent Neural Network To Inform the Use of Prostate-specific Antigen (PSA) and PSA Density for Dynamic Monitoring of the Risk of Prostate Cancer Progression on Active Surveillance

The global uptake of prostate cancer (PCa) active surveillance (AS) is steadily increasing. While prostate-specific antigen density (PSAD) is an important baseline predictor of PCa progression on AS, there is a scarcity of recommendations on its use in follow-up. In particular, the best way of measuring PSAD is unclear. One approach would be to use the baseline gland volume (BGV) as a denominator in all calculations throughout AS (nonadaptive PSAD, PSADNA), while another would be to remeasure gland volume at each new magnetic resonance imaging scan (adaptive PSAD, PSADA). In addition, little is known about the predictive value of serial PSAD in comparison to PSA. We applied a long short-term memory recurrent neural network to an AS cohort of 332 patients and found that serial PSADNA significantly outperformed both PSADA and PSA for follow-up prediction of PCa progression because of its high sensitivity. Importantly, while PSADNA was superior in patients with smaller glands (BGV ≤55 ml), serial PSA was better in men with larger prostates of >55 ml. Patient summary: Repeat measurements of prostate-specific antigen (PSA) and PSA density (PSAD) are the mainstay of active surveillance in prostate cancer. Our study suggests that in patients with a prostate gland of 55 ml or smaller, PSAD measurements are a better predictor of tumour progression, whereas men with a larger gland may benefit more from PSA monitoring

MRI features of the normal prostatic peripheral zone: the relationship between age and signal heterogeneity on T2WI, DWI, and DCE sequences

Funder: University of CambridgeAbstract: Objectives: To assess the multiparametric MRI (mpMRI) appearances of normal peripheral zone (PZ) across age groups in a biopsy-naïve population, where prostate cancer (PCa) was subsequently excluded, and propose a scoring system for background PZ changes. Methods: This retrospective study included 175 consecutive biopsy-naïve patients (40–74 years) referred with a suspicion of PCa, but with subsequent negative investigations. Patients were grouped by age into categories ≤ 54, 55–59, 60–64, and ≥ 65 years. MpMRI sequences (T2-weighted imaging [T2WI], diffusion-weighted imaging [DWI]/apparent diffusion coefficient [ADC], and dynamic contrast-enhanced imaging [DCE]) were independently evaluated by two uro-radiologists on a proposed 4-point grading scale for background change on each sequence, wherein score 1 mirrored PIRADS-1 change and score 4 represented diffuse background change. Peripheral zone T2WI signal intensity and ADC values were also analyzed for trends relating to age. Results: There was a negative correlation between age and assigned background PZ scores for each mpMRI sequence: T2WI: r = − 0.52, DWI: r = − 0.49, DCE: r = − 0.45, p < 0.001. Patients aged ≤ 54 years had mean scores of 3.0 (T2WI), 2.7 (DWI), and 3.1 (DCE), whilst patients ≥ 65 years had significantly lower mean scores of 1.7, 1.4, and 1.9, respectively. There was moderate inter-reader agreement for all scores (range κ = 0.43–0.58). Statistically significant positive correlations were found for age versus normalized T2WI signal intensity (r = 0.2, p = 0.009) and age versus ADC values (r = 0.33, p = 0.001). Conclusion: The normal PZ in younger patients (≤ 54 years) demonstrates significantly lower T2WI signal intensity, lower ADC values, and diffuse enhancement on DCE, which may hinder diagnostic interpretation in these patients. The proposed standardized PZ background scoring system may help convey the potential for diagnostic uncertainty to clinicians. Key Points: • Significant, positive correlations were found between increasing age and higher normalized T2-weighted signal intensity and mean ADC values of the prostatic peripheral zone. • Younger men exhibit lower T2-weighted imaging signal intensity, lower ADC values, and diffuse enhancement on dynamic contrast-enhanced imaging, which may hinder MRI interpretation. • A scoring system is proposed which aims towards a standardized assessment of the normal background PZ. This may help convey the potential for diagnostic uncertainty to clinicians

MRI-derived PRECISE scores for predicting pathologically-confirmed radiological progression in prostate cancer patients on active surveillance

Funder: University of CambridgeAbstract: Objectives: To assess the predictive value and correlation to pathological progression of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scoring system in the follow-up of prostate cancer (PCa) patients on active surveillance (AS). Methods: A total of 295 men enrolled on an AS programme between 2011 and 2018 were included. Baseline multiparametric magnetic resonance imaging (mpMRI) was performed at AS entry to guide biopsy. The follow-up mpMRI studies were prospectively reported by two sub-specialist uroradiologists with 10 years and 13 years of experience. PRECISE scores were dichotomized at the cut-off value of 4, and the sensitivity, specificity, positive predictive value and negative predictive value were calculated. Diagnostic performance was further quantified by using area under the receiver operating curve (AUC) which was based on the results of targeted MRI-US fusion biopsy. Univariate analysis using Cox regression was performed to assess which baseline clinical and mpMRI parameters were related to disease progression on AS. Results: Progression rate of the cohort was 13.9% (41/295) over a median follow-up of 52 months. With a cut-off value of category ≥ 4, the PRECISE scoring system showed sensitivity, specificity, PPV and NPV for predicting progression on AS of 0.76, 0.89, 0.52 and 0.96, respectively. The AUC was 0.82 (95% CI = 0.74–0.90). Prostate-specific antigen density (PSA-D), Likert lesion score and index lesion size were the only significant baseline predictors of progression (each p < 0.05). Conclusion: The PRECISE scoring system showed good overall performance, and the high NPV may help limit the number of follow-up biopsies required in patients on AS. Key Points: • PRECISE scores 1–3 have high NPV which could reduce the need for re-biopsy during active surveillance. • PRECISE scores 4–5 have moderate PPV and should trigger either close monitoring or re-biopsy. • Three baseline predictors (PSA density, lesion size and Likert score) have a significant impact on the progression-free survival (PFS) time

MRI-derived PRECISE scores for predicting pathologically-confirmed radiological progression in prostate cancer patients on active surveillance

Funder: University of CambridgeAbstract: Objectives: To assess the predictive value and correlation to pathological progression of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scoring system in the follow-up of prostate cancer (PCa) patients on active surveillance (AS). Methods: A total of 295 men enrolled on an AS programme between 2011 and 2018 were included. Baseline multiparametric magnetic resonance imaging (mpMRI) was performed at AS entry to guide biopsy. The follow-up mpMRI studies were prospectively reported by two sub-specialist uroradiologists with 10 years and 13 years of experience. PRECISE scores were dichotomized at the cut-off value of 4, and the sensitivity, specificity, positive predictive value and negative predictive value were calculated. Diagnostic performance was further quantified by using area under the receiver operating curve (AUC) which was based on the results of targeted MRI-US fusion biopsy. Univariate analysis using Cox regression was performed to assess which baseline clinical and mpMRI parameters were related to disease progression on AS. Results: Progression rate of the cohort was 13.9% (41/295) over a median follow-up of 52 months. With a cut-off value of category ≥ 4, the PRECISE scoring system showed sensitivity, specificity, PPV and NPV for predicting progression on AS of 0.76, 0.89, 0.52 and 0.96, respectively. The AUC was 0.82 (95% CI = 0.74–0.90). Prostate-specific antigen density (PSA-D), Likert lesion score and index lesion size were the only significant baseline predictors of progression (each p < 0.05). Conclusion: The PRECISE scoring system showed good overall performance, and the high NPV may help limit the number of follow-up biopsies required in patients on AS. Key Points: • PRECISE scores 1–3 have high NPV which could reduce the need for re-biopsy during active surveillance. • PRECISE scores 4–5 have moderate PPV and should trigger either close monitoring or re-biopsy. • Three baseline predictors (PSA density, lesion size and Likert score) have a significant impact on the progression-free survival (PFS) time

Infection of XC Cells by MLVs and Ebola Virus Is Endosome-Dependent but Acidification-Independent

Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously shown, the endosome acidification inhibitors did not inhibit these viral infections in XC cells. It is generally accepted that the ecotropic MLV infection in XC cells occurs at the plasma membrane. Because cathepsin proteases are activated by low pH in acidic endosomes, the acidification inhibitors may inhibit the viral infections by suppressing cathepsin protease activation. The acidification inhibitors attenuated the activities of cathepsin proteases B and L in TE671 cells, but not in XC cells. Processing of cathepsin protease L was suppressed by the acidification inhibitor in NIH3T3 cells, but again not in XC cells. These results indicate that cathepsin proteases are activated without endosome acidification in XC cells. Treatment with an endocytosis inhibitor or knockdown of dynamin 2 expression by siRNAs suppressed MLV infections in all examined cells including XC cells. Furthermore, endosomal cathepsin proteases were required for these viral infections in XC cells as other susceptible cells. These results suggest that infections of XC cells by the MLVs and Ebola virus occur through endosomes and pH-independent cathepsin activation induces pH-independent infection in XC cells

Profiling Trait Anxiety: Transcriptome Analysis Reveals Cathepsin B (Ctsb) as a Novel Candidate Gene for Emotionality in Mice

Behavioral endophenotypes are determined by a multitude of counteracting but precisely balanced molecular and physiological mechanisms. In this study, we aim to identify potential novel molecular targets that contribute to the multigenic trait “anxiety”. We used microarrays to investigate the gene expression profiles of different brain regions within the limbic system of mice which were selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, and also show signs of comorbid depression-like behavior

National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection - recommendations from a UK consensus meeting.

OBJECTIVES: To identify areas of agreement and disagreement in the implementation of multi-parametric magnetic resonance imaging (mpMRI) of the prostate in the diagnostic pathway. MATERIALS AND METHODS: Fifteen UK experts in prostate mpMRI and/or prostate cancer management across the UK (involving nine NHS centres to provide for geographical spread) participated in a consensus meeting following the Research and Development Corporation and University of California-Los Angeles (UCLA-RAND) Appropriateness Method, and were moderated by an independent chair. The experts considered 354 items pertaining to who can request an mpMRI, prostate mpMRI protocol, reporting guidelines, training, quality assurance (QA) and patient management based on mpMRI levels of suspicion for cancer. Each item was rated for agreement on a 9-point scale. A panel median score of ≥7 constituted 'agreement' for an item; for an item to reach 'consensus', a panel majority scoring was required. RESULTS: Consensus was reached on 59% of items (208/354); these were used to provide recommendations for the implementation of prostate mpMRI in the UK. Key findings include prostate mpMRI requests should be made in consultation with the urological team; mpMRI scanners should undergo QA checks to guarantee consistently high diagnostic quality scans; scans should only be reported by trained and experienced radiologists to ensure that men with unsuspicious prostate mpMRI might consider avoiding an immediate biopsy. CONCLUSIONS: Our consensus statements demonstrate a set of criteria that are required for the practical dissemination of consistently high-quality prostate mpMRI as a diagnostic test before biopsy in men at risk