Spatiotemporal analysis of contrast-enhanced ultrasound for differentiating between malignant and benign breast lesions.

OBJECTIVES: The aim of this study was to apply spatiotemporal analysis of contrast-enhanced ultrasound (CEUS) loops to quantify the enhancement heterogeneity for improving the differentiation between benign and malignant breast lesions. MATERIALS AND METHODS: This retrospective study included 120 women (age range, 18-82 years; mean, 52 years) scheduled for ultrasound-guided biopsy. With the aid of brightness-mode images, the border of each breast lesion was delineated in the CEUS images. Based on visual evaluation and quantitative metrics, the breast lesions were categorized into four grades of different levels of contrast enhancement. Grade-1 (hyper-enhanced) and grade-2 (partly-enhanced) breast lesions were included in the analysis. Four parameters reflecting enhancement heterogeneity were estimated by spatiotemporal analysis of neighboring time-intensity curves (TICs). By setting the threshold on mean parameter, the diagnostic performance of the four parameters for differentiating benign and malignant lesions was evaluated. RESULTS: Sixty-four of the 120 patients were categorized as grade 1 or 2 and used for estimating the four parameters. At the pixel level, mutual information and conditional entropy present significantly different values between the benign and malignant lesions (p < 0.001 in patients of grade 1, p = 0.002 in patients of grade 1 or 2). For the classification of breast lesions, mutual information produces the best diagnostic performance (AUC = 0.893 in patients of grade 1, AUC = 0.848 in patients of grade 1 or 2). CONCLUSIONS: The proposed spatiotemporal analysis for assessing the enhancement heterogeneity shows promising results to aid in the diagnosis of breast cancer by CEUS. CLINICAL RELEVANCE STATEMENT: The proposed spatiotemporal method can be developed as a standardized software to automatically quantify the enhancement heterogeneity of breast cancer on CEUS, possibly leading to the improved diagnostic accuracy of differentiation between benign and malignant lesions. KEY POINTS: • Advanced spatiotemporal analysis of ultrasound contrast-enhanced loops for aiding the differentiation of malignant or benign breast lesions. • Four parameters reflecting the enhancement heterogeneity were estimated in the hyper- and partly-enhanced breast lesions by analyzing the neighboring pixel-level time-intensity curves. • For the classification of hyper-enhanced breast lesions, mutual information produces the best diagnostic performance (AUC = 0.893).

A review on B/A measurement methods with a clinical perspective.

The nonlinear parameter of ultrasound B/A has shown to be a useful diagnostic parameter, reflecting medium content, structure, and temperature. Despite its recognized values, B/A is not yet used as a diagnostic tool in the clinic due to the limitations of current measurement and imaging techniques. This review presents an extensive and comprehensive overview of the techniques developed for B/A measurement of liquid and liquid-like media (e.g., tissue), identifying the methods that are most promising from a clinical perspective. This work summarizes the progress made in the field and the typical challenges on the way to B/A estimation. Limitations and problems with the current techniques are identified, suggesting directions that may lead to further improvement. Since the basic theory of the physics behind the measurement strategies is presented, it is also suited for a reader who is new to nonlinear ultrasound.

Detection of clinically significant prostate cancer in biopsy-naïve men: direct comparison of systematic biopsy, multiparametric MRI- and contrast-ultrasound-dispersion imaging-targeted biopsy.

OBJECTIVES: To compare and evaluate a multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (TBx) strategy, contrast-ultrasound-dispersion imaging (CUDI)-TBx strategy and systematic biopsy (SBx) strategy for the detection of clinically significant prostate cancer (csPCa) in biopsy-naïve men. PATIENTS AND METHODS: A prospective, single-centre paired diagnostic study included 150 biopsy-naïve men, from November 2015 to November 2018. All men underwent pre-biopsy mpMRI and CUDI followed by a 12-core SBx taken by an operator blinded from the imaging results. Men with suspicious lesions on mpMRI and/or CUDI also underwent MRI-TRUS fusion-TBx and/or cognitive CUDI-TBx after SBx by a second operator. A non-inferiority analysis of the mpMRI- and CUDI-TBx strategies in comparison with SBx for International Society of Urological Pathology Grade Group [GG] ≥2 PCa in any core with a non-inferiority margin of 1 percentage point was performed. Additional analyses for GG ≥2 PCa with cribriform growth pattern and/or intraductal carcinoma (CR/IDC), and GG ≥3 PCa were performed. Differences in detection rates were tested using McNemar's test with adjusted Wald confidence intervals. RESULTS: After enrolment of 150 men, an interim analysis was performed. Both the mpMRI- and CUDI-TBx strategies were inferior to SBx for GG ≥2 PCa detection and the study was stopped. SBx found significantly more GG ≥2 PCa: 39% (56/142), as compared with 29% (41/142) and 28% (40/142) for mpMRI-TBx and CUDI-TBx, respectively (P < 0.05). SBx found significantly more GG = 1 PCa: 14% (20/142) compared to 1% (two of 142) and 3% (four of 142) with mpMRI-TBx and CUDI-TBx, respectively (P < 0.05). Detection of GG ≥2 PCa with CR/IDC and GG ≥3 PCa did not differ significantly between the strategies. The mpMRI- and CUDI-TBx strategies were comparable in detection but the mpMRI-TBx strategy had less false-positive findings (18% vs 53%). CONCLUSIONS: In our study in biopsy-naïve men, the mpMRI- and CUDI-TBx strategies had comparable PCa detection rates, but the mpMRI-TBX strategy had the least false-positive findings. Both strategies were inferior to SBx for the detection of GG ≥2 PCa, despite reduced detection of insignificant GG = 1 PCa. Both strategies did not significantly differ from SBx for the detection of GG ≥2 PCa with CR/IDC and GG ≥3 PCa.

Contrast-enhanced ultrasound with dispersion analysis for the localization of prostate cancer: correlation with radical prostatectomy specimens.

PURPOSE: To determine the value of two-dimensional (2D) contrast-enhanced ultrasound (CEUS) imaging and the additional value of contrast ultrasound dispersion imaging (CUDI) for the localization of clinically significant prostate cancer (csPCa). METHODS: In this multicentre study, subjects scheduled for a radical prostatectomy underwent 2D CEUS imaging preoperatively. CUDI maps were generated from the CEUS recordings. Both CEUS recordings and CUDI maps were scored on the likelihood of presenting csPCa (any Gleason ≥ 4 + 3 and Gleason 3 + 4 larger than 0.5 mL) by five observers and compared to radical prostatectomy histopathology. An automated three-dimensional (3D) fusion protocol was used to match imaging with histopathology. Receiver operator curve (ROC) analysis was performed per observer and imaging modality. RESULTS: 133 of 216 (62%) patients were included in the final analysis. Average area under the ROC for all five readers for CEUS, CUDI and the combination was 0.78, 0.79 and 0.78, respectively. This yields a sensitivity and specificity of 81 and 64% for CEUS, 83 and 56% for CUDI and 83 and 55% for the combination. Interobserver agreement for CEUS, CUDI and the combination showed kappa values of 0.20, 0.18 and 0.18 respectively. CONCLUSION: The sensitivity and specificity of 2D CEUS and CUDI for csPCa localization are moderate. Despite compressing CEUS in one image, CUDI showed a similar performance to 2D CEUS. With a sensitivity of 83% at cutoff point 3, it could become a useful imaging procedure, especially with 4D acquisition, improved quantification and combination with other US imaging techniques such as elastography.

Automated multiparametric localization of prostate cancer based on B-mode, shear-wave elastography, and contrast-enhanced ultrasound radiomics.

OBJECTIVES: The aim of this study was to assess the potential of machine learning based on B-mode, shear-wave elastography (SWE), and dynamic contrast-enhanced ultrasound (DCE-US) radiomics for the localization of prostate cancer (PCa) lesions using transrectal ultrasound. METHODS: This study was approved by the institutional review board and comprised 50 men with biopsy-confirmed PCa that were referred for radical prostatectomy. Prior to surgery, patients received transrectal ultrasound (TRUS), SWE, and DCE-US for three imaging planes. The images were automatically segmented and registered. First, model-based features related to contrast perfusion and dispersion were extracted from the DCE-US videos. Subsequently, radiomics were retrieved from all modalities. Machine learning was applied through a random forest classification algorithm, using the co-registered histopathology from the radical prostatectomy specimens as a reference to draw benign and malignant regions of interest. To avoid overfitting, the performance of the multiparametric classifier was assessed through leave-one-patient-out cross-validation. RESULTS: The multiparametric classifier reached a region-wise area under the receiver operating characteristics curve (ROC-AUC) of 0.75 and 0.90 for PCa and Gleason > 3 + 4 significant PCa, respectively, thereby outperforming the best-performing single parameter (i.e., contrast velocity) yielding ROC-AUCs of 0.69 and 0.76, respectively. Machine learning revealed that combinations between perfusion-, dispersion-, and elasticity-related features were favored. CONCLUSIONS: In this paper, technical feasibility of multiparametric machine learning to improve upon single US modalities for the localization of PCa has been demonstrated. Extended datasets for training and testing may establish the clinical value of automatic multiparametric US classification in the early diagnosis of PCa. KEY POINTS: • Combination of B-mode ultrasound, shear-wave elastography, and contrast ultrasound radiomics through machine learning is technically feasible. • Multiparametric ultrasound demonstrated a higher prostate cancer localization ability than single ultrasound modalities. • Computer-aided multiparametric ultrasound could help clinicians in biopsy targeting.

Multiparametric Ultrasound for Prostate Cancer Detection and Localization: Correlation of B-mode, Shear Wave Elastography and Contrast Enhanced Ultrasound with Radical Prostatectomy Specimens.

PURPOSE: Similar to multiparametric magnetic resonance imaging, multiparametric ultrasound represents a promising approach to prostate cancer imaging. We determined the diagnostic performance of B-mode, shear wave elastography and contrast enhanced ultrasound with quantification software as well as the combination, multiparametric ultrasound, for clinically significant prostate cancer localization using radical prostatectomy histopathology as the reference standard. MATERIALS AND METHODS: From May 2017 to July 2017, 50 men with biopsy proven prostate cancer underwent multiparametric ultrasound before radical prostatectomy at 1 center. Three readers independently evaluated 12 anatomical regions of interest for the likelihood of clinically significant prostate cancer on a 5-point Likert scale for all separate ultrasound modalities and multiparametric ultrasound. A logistic linear mixed model was used to estimate diagnostic performance for the localization of clinically significant prostate cancer (any tumor with Gleason score 3 + 4 = 7 or greater, tumor volume 0.5 ml or greater, extraprostatic extension or stage pN1) using a Likert score of 3 or greater and 4 or greater as the threshold. To detect the index lesion the readers selected the 2 most suspicious regions of interest. RESULTS: A total of 48 men were included in the final analysis. The region of interest specific sensitivity of multiparametric ultrasound (Likert 3 or greater) for clinically significant prostate cancer was 74% (95% CI 67-80) compared to 55% (95% CI 47-63), 55% (95% CI 47-63) and 59% (95% CI 51-67) for B-mode, shear wave elastography and contrast enhanced ultrasound, respectively. Multiparametric ultrasound sensitivity was significantly higher for Likert thresholds and all different clinically significant prostate cancer definitions (all p <0.05). Multiparametric ultrasound improved the detection of index lesion prostate cancer. CONCLUSIONS: Multiparametric ultrasound of the prostate, consisting of B-mode, shear wave elastography and contrast enhanced ultrasound with parametric maps, improved localization and index lesion detection of clinically significant prostate cancer compared to single ultrasound modalities, yielding good sensitivity.

Three-dimensional greyscale transrectal ultrasound-guidance and biopsy core preembedding for detection of prostate cancer: Dutch clinical cohort study.

BACKGROUND: To overcome the limitations regarding two dimensional (2D) greyscale (GS) transrectal ultrasound (TRUS)-guided biopsy in prostate cancer (PCa) detection and tissue packaging in biopsy processing, there is an ongoing focus on new imaging and pathology techniques. A three-dimensional (3D) model of the prostate with biopsy needle guidance can be generate by the Navigo™ workstation (UC-care, Israel). The SmartBX™ system (UC-care, Israel) provides a prostate biopsy core preembedding method. The aim of this study was to compare cancer detection rates between the 3D TRUS-guidance and preembedding method with conventional 2D GS TRUS-guidance among patients undergoing prostate biopsies. METHODS: We retrospectively analyzed the records of all patients who underwent prostate biopsies for PCa detection at our institution from 2007 to 2016. The cohort was divided into a 2D GS TRUS-guidance cohort (from 2007 to 2013, n = 1149) and a 3D GS TRUS-guidance with preembedding cohort (from 2013 to 2016, n = 469). Effect of 3D GS TRUS-guidance with preembedding on detection rate of PCa and clinically significant PCa (Gleason score ≥ 7 or > 2 biopsy cores with a Gleason score 6) was compared to 2D GS TRUS-guidance using regression models. RESULTS: Detection rate of PCa and clinically significant PCa was 39.0 and 24.9% in the 3D GS TRUS cohort compared to 33.5 and 19.0% in the 2D GS TRUS cohort, respectively. On multivariate regression analysis the use of 3D GS TRUS-guidance with preembedding was associated with a significant increase in detection rate of PCa (aOR = 1.33; 95% CI: 1.03-1.72) and clinically significant PCa (aOR = 1.47; 95% CI: 1.09-1.98). CONCLUSION: Our results suggest that 3D GS TRUS-guidance with biopsy core preembedding improves PCa and clinically significant PCa detection compared to 2D GS TRUS-guidance. Additional studies are needed to justify the application of these systems in clinical practice.

Validation of the Electronic Version of the International Index of Erectile Function (IIEF-5 and IIEF-15): A Crossover Study.

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly used to measure patient's perspective of functional well-being, disease burden, treatment effectiveness, and clinical decision making. Electronic versions are increasingly feasible because of smartphone and tablet usage. However, validation of these electronic PROMs (ePROMs) is warranted for justified implementation. The International Index of Erectile Function (IIEF) 5 and 15 are widely used PROMs in urology to measure erectile dysfunction. Measurement reliability and validity testing of the IIEF ePROMs are essential before clinical application. OBJECTIVE: The aim of this study was to assess reliability and validity of an ePROM version of both IIEF-5 and 15. METHODS: This study included 179 patients from our urology outpatient clinic. It also had a randomized crossover design-participants completed either a paper and electronic IIEF-5 or 15 or twice completed an electronic version-with a 5-day delay. Internal consistency was assessed using Cronbach alpha and Spearman-Brown coefficient, test-retest reliability using the intraclass correlation coefficient (ICC), and convergent validity using the Pearson and Spearman correlation coefficient. RESULTS: A total of 122 participants completed the study. Internal consistency was excellent for the electronic IIEF-5 (ICC 0.902) and good to excellent for the domains of the IIEF-15 (ICC 0.962-0.834). Test-retest reliability was excellent for the IIEF-5 (ICC 0.924) and good to excellent for the domains of the IIEF-15 (ICC 0.950-0.778). Convergent validity was excellent for the IIEF-5 and IIEF-15, with a correlation of r=0.923 and r=0.951, respectively. CONCLUSIONS: We successfully introduced patient-acceptable ePROM versions of the IIEF-5 and IIEF-15. This study's results demonstrate that the ePROM versions of the IIEF-5 and IIEF-15 can be reliably implemented, as outcomes are reliable and in accordance with findings of the paper version. TRIAL REGISTRATION: ClinicalTrials.gov NCT03222388; https://clinicaltrials.gov/ct2/show/NCT03222388.

Concordance of Gleason grading with three-dimensional ultrasound systematic biopsy and biopsy core pre-embedding.

PURPOSE: To determine the value of a three-dimensional (3D) greyscale transrectal ultrasound (TRUS)-guided prostate biopsy system and biopsy core pre-embedding method on concordance between Gleason scores of needle biopsies and radical prostatectomy (RP) specimens. METHODS: Retrospective analysis of prostate biopsies and subsequent RP for PCa in the Jeroen Bosch Hospital, the Netherlands, from 2007 to 2016. Two cohorts were analysed: conventional 2D TRUS-guided biopsies and RP (2007-2013, n = 266) versus 3D TRUS-guided biopsies with pre-embedding (2013-2016, n = 129). The impact of 3D TRUS-guidance with pre-embedding on Gleason score (GS) concordance between biopsy and RP was evaluated using the κ-coefficient. Predictors of biopsy GS 6 upgrading were assessed using logistic regression models. RESULTS: Gleason concordance was comparable between the two cohorts with a κ = 0.44 for the 3D cohort, compared to κ = 0.42 for the 2D cohort. 3D TRUS-guidance with pre-embedding, did not significantly affect the risk of biopsy GS 6 upgrading in univariate and multivariate analysis. CONCLUSIONS: 3D TRUS-guidance with biopsy core pre-embedding did not improve Gleason concordance. Improved detection techniques are needed for recognition of low-grade disease upgrading.

Evaluation of Dispersion MRI for Improved Prostate Cancer Diagnosis in a Multicenter Study.

OBJECTIVE: The purpose of this study is to compare dispersion MRI and Tofts model (TM) for analysis of quantitative dynamic contrast-enhanced (DCE) MRI (DCE-MRI) for localization of prostate cancer and to assess the correlation between quantitative DCE-MRI parameters and tumor grade. MATERIALS AND METHODS: This retrospective multicenter study included 80 patients with biopsy-proven prostate cancer who underwent DCE-MRI followed by radical prostatectomy. DCE-MRI parameters were extracted from dispersion MRI analysis (the dispersion parameter [kd], the flux rate [kep], and the intravascular mean transit time) and TM analysis (the forward volume transfer constant [Ktrans], kep, and the extravascular extracellular volume fraction [ve]). ROIs representing benign and malignant tissue were drawn on each DCE-MRI slice according to the histopathologic findings, and the diagnostic performance of the estimated parameters for the diagnosis of prostate cancer was evaluated using fivefold cross-validation and ROC curve analysis. Further analysis was conducted for the two most relevant parameters (i.e., kd [for dispersion MRI] and kep [for TM]), to investigate the correlation between DCE-MRI parameters and tumor grade. RESULTS: DCE-MRI parameters were significantly different between benign and malignant prostate tissue (p < 0.0001). The dispersion MRI parameter kd outperformed all other DCE-MRI parameters for prostate cancer diagnosis, showing the highest area under the ROC curve value (p < 0.0001). Only a weak linear correlation (Pearson r = 0.18; p < 0.05) was found between the dispersion parameter and the Gleason grade group. CONCLUSION: Dispersion MRI outperformed TM analysis, improving the diagnostic performance of quantitative DCE-MRI for prostate cancer localization. Of the DCE-MRI parameters, kd (for dispersion MRI) and kep (for TM) provided only poor characterization of tumor grade.

Multiparametric ultrasound: evaluation of greyscale, shear wave elastography and contrast-enhanced ultrasound for prostate cancer detection and localization in correlation to radical prostatectomy specimens.

BACKGROUND: The diagnostic pathway for prostate cancer (PCa) is advancing towards an imaging-driven approach. Multiparametric magnetic resonance imaging, although increasingly used, has not shown sufficient accuracy to replace biopsy for now. The introduction of new ultrasound (US) modalities, such as quantitative contrast-enhanced US (CEUS) and shear wave elastography (SWE), shows promise but is not evidenced by sufficient high quality studies, especially for the combination of different US modalities. The primary objective of this study is to determine the individual and complementary diagnostic performance of greyscale US (GS), SWE, CEUS and their combination, multiparametric ultrasound (mpUS), for the detection and localization of PCa by comparison with corresponding histopathology. METHODS/DESIGN: In this prospective clinical trial, US imaging consisting of GS, SWE and CEUS with quantitative mapping on 3 prostate imaging planes (base, mid and apex) will be performed in 50 patients with biopsy-proven PCa before planned radical prostatectomy using a clinical ultrasound scanner. All US imaging will be evaluated by US readers, scoring the four quadrants of each imaging plane for the likelihood of significant PCa based on a 1 to 5 Likert Scale. Following resection, PCa tumour foci will be identified, graded and attributed to the imaging-derived quadrants in each prostate plane for all prostatectomy specimens. Primary outcome measure will be the sensitivity, specificity, negative predictive value and positive predictive value of each US modality and mpUS to detect and localize significant PCa evaluated for different Likert Scale thresholds using receiver operating characteristics curve analyses. DISCUSSION: In the evaluation of new PCa imaging modalities, a structured comparison with gold standard radical prostatectomy specimens is essential as first step. This trial is the first to combine the most promising ultrasound modalities into mpUS. It complies with the IDEAL stage 2b recommendations and will be an important step towards the evaluation of mpUS as a possible option for accurate detection and localization of PCa. TRIAL REGISTRATION: The study protocol for multiparametric ultrasound was prospectively registered on Clinicaltrials.gov on 14 March 2017 with the registry name 'Multiparametric Ultrasound-Study for the Detection of Prostate Cancer' and trial registration number NCT03091231.

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).

The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Short Version).

The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.

Multiparametric dynamic contrast-enhanced ultrasound imaging of prostate cancer.

OBJECTIVES: The aim of this study is to improve the accuracy of dynamic contrast-enhanced ultrasound (DCE-US) for prostate cancer (PCa) localization by means of a multiparametric approach. MATERIALS AND METHODS: Thirteen different parameters related to either perfusion or dispersion were extracted pixel-by-pixel from 45 DCE-US recordings in 19 patients referred for radical prostatectomy. Multiparametric maps were retrospectively produced using a Gaussian mixture model algorithm. These were subsequently evaluated on their pixel-wise performance in classifying 43 benign and 42 malignant histopathologically confirmed regions of interest, using a prostate-based leave-one-out procedure. RESULTS: The combination of the spatiotemporal correlation (r), mean transit time (µ), curve skewness (κ), and peak time (PT) yielded an accuracy of 81% ± 11%, which was higher than the best performing single parameters: r (73%), µ (72%), and wash-in time (72%). The negative predictive value increased to 83% ± 16% from 70%, 69% and 67%, respectively. Pixel inclusion based on the confidence level boosted these measures to 90% with half of the pixels excluded, but without disregarding any prostate or region. CONCLUSIONS: Our results suggest multiparametric DCE-US analysis might be a useful diagnostic tool for PCa, possibly supporting future targeting of biopsies or therapy. Application in other types of cancer can also be foreseen. KEY POINTS: • DCE-US can be used to extract both perfusion and dispersion-related parameters. • Multiparametric DCE-US performs better in detecting PCa than single-parametric DCE-US. • Multiparametric DCE-US might become a useful tool for PCa localization.

Focal vs extended ablation in localized prostate cancer with irreversible electroporation; a multi-center randomized controlled trial.

BACKGROUND: 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. METHODS/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: Clinicaltrials.gov database registration number NCT01835977. The Dutch Central Committee on Research Involving Human Subjects registration number NL50791.018.14.

The value of magnetic resonance imaging and ultrasonography (MRI/US)-fusion biopsy platforms in prostate cancer detection: a systematic review.

Despite limitations considering the presence, staging and aggressiveness of prostate cancer, ultrasonography (US)-guided systematic biopsies (SBs) are still the 'gold standard' for the diagnosis of prostate cancer. Recently, promising results have been published for targeted prostate biopsies (TBs) using magnetic resonance imaging (MRI) and ultrasonography (MRI/US)-fusion platforms. Different platforms are USA Food and Drug Administration registered and have, mostly subjective, strengths and weaknesses. To our knowledge, no systematic review exists that objectively compares prostate cancer detection rates between the different platforms available. To assess the value of the different MRI/US-fusion platforms in prostate cancer detection, we compared platform-guided TB with SB, and other ways of MRI TB (cognitive fusion or in-bore MR fusion). We performed a systematic review of well-designed prospective randomised and non-randomised trials in the English language published between 1 January 2004 and 17 February 2015, using PubMed, Embase and Cochrane Library databases. Search terms included: 'prostate cancer', 'MR/ultrasound(US) fusion' and 'targeted biopsies'. Extraction of articles was performed by two authors (M.G. and A.A.) and were evaluated by the other authors. Randomised and non-randomised prospective clinical trials comparing TB using MRI/US-fusion platforms and SB, or other ways of TB (cognitive fusion or MR in-bore fusion) were included. In all, 11 of 1865 studies met the inclusion criteria, involving seven different fusion platforms and 2626 patients: 1119 biopsy naïve, 1433 with prior negative biopsy, 50 not mentioned (either biopsy naïve or with prior negative biopsy) and 24 on active surveillance (who were disregarded). The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to assess the quality of included articles. No clear advantage of MRI/US fusion-guided TBs was seen for cancer detection rates (CDRs) of all prostate cancers. However, MRI/US fusion-guided TBs tended to give higher CDRs for clinically significant prostate cancers in our analysis. Important limitations of the present systematic review include: the limited number of included studies, lack of a general definition of 'clinically significant' prostate cancer, the heterogeneous study population, and a reference test with low sensitivity and specificity. Today, a limited number of prospective studies have reported the CDRs of fusion platforms. Although MRI/US-fusion TB has proved its value in men with prior negative biopsies, general use of this technique in diagnosing prostate cancer should only be performed after critical consideration. Before bringing MRI/US fusion-guided TB in to general practice, there is a need for more prospective studies on prostate cancer diagnosis.

Dynamic contrast-enhanced ultrasound parametric imaging for the detection of prostate cancer.

OBJECTIVE: To investigate the value of dynamic contrast-enhanced (DCE)-ultrasonography (US) and software-generated parametric maps in predicting biopsy outcome and their potential to reduce the amount of negative biopsy cores. MATERIALS AND METHODS: For 651 prostate biopsy locations (82 consecutive patients) we correlated the interpretation of DCE-US recordings with and without parametric maps with biopsy results. The parametric maps were generated by software which extracts perfusion parameters that differentiate benign from malignant tissue from DCE-US recordings. We performed a stringent analysis (all tumours) and a clinical analysis (clinically significant tumours). We calculated the potential reduction in biopsies (benign on imaging) and the resultant missed positive biopsies (false-negatives). Additionally, we evaluated the performance in terms of sensitivity, specificity negative predictive value (NPV) and positive predictive value (PPV) on a per-prostate level. RESULTS: Based on DCE-US, 470/651 (72.2%) of biopsy locations appeared benign, resulting in 40 false-negatives (8.5%), considering clinically significant tumours only. Including parametric maps, 411/651 (63.1%) of the biopsy locations appeared benign, resulting in 23 false-negatives (5.6%). In the per-prostate clinical analysis, DCE-US classified 38/82 prostates as benign, missing eight diagnoses. Including parametric maps, 31/82 prostates appeared benign, missing three diagnoses. Sensitivity, specificity, PPV and NPV were 73, 58, 50 and 79%, respectively, for DCE-US alone and 91, 56, 57 and 90%, respectively, with parametric maps. CONCLUSION: The interpretation of DCE-US with parametric maps allows good prediction of biopsy outcome. A two-thirds reduction in biopsy cores seems feasible with only a modest decrease in cancer diagnosis.

3D Navigo™ versus TRUS-guided prostate biopsy in prostate cancer detection.

INTRODUCTION: To overcome the limitations regarding transrectal ultrasound (TRUS)-guided biopsies in prostate cancer (PCa) detection, there is a focus on new imaging technologies. The Navigo™ system (UC-care, Israel) uses regular TRUS images and electrospatial monitoring to generate a 3D model of the prostate. The aim of this study was to compare cancer detection rates between the Navigo™ system and conventional TRUS, in patients without a history of PCa. METHODS: We performed a retrospective study by collecting data from all patients who underwent 12-core prostate biopsies from lateral peripheral zones between September 2013 and February 2015 at the Jeroen Bosch Hospital in 's-Hertogenbosch (Netherlands). RESULTS: A total of 325 patients met our inclusion criteria. 77.8 % of biopsy sessions were performed using the Navigo™ system. There was no statistically significant difference in PCa detection (39.9 vs 46.2 % with Navigo™ system and TRUS, respectively). Using the Navigo™ system for taking prostate biopsies proved not to be associated with the presence of PCa at biopsy, likewise for clinically significant PCa and for both subgroups. LIMITATIONS: The limitations of the study include its retrospective design, the limited number of patients in the conventional TRUS group, the statistically significant different number of biopsy sessions and the ones performed by an advanced physician in both groups. CONCLUSION: In our study, there is no added value of 3D TRUS using Navigo™ system compared to conventional 2D TRUS regarding PCa detection in biopsy-naive men and men with prior negative biopsy.

Bladder wall thickness in women with symptoms of overactive bladder and detrusor overactivity: Results from the randomised, placebo-controlled shrink study.

AIMS: Measurement of bladder wall thickness (BWT) by transvaginal ultrasound (TVUS) may be a less invasive method to diagnose overactive bladder (OAB) or detrusor overactivity (DO) and monitor response to therapy. This study assessed whether treatment with solifenacin affects BWT. METHODS: This was a double-blind, randomised, placebo-controlled, phase 4 study. Adult women with OAB symptoms received solifenacin 5 or 10 mg or placebo once daily for 12 weeks. The co-primary endpoints were change from baseline to Week 12 in TVUS-measured BWT and urinary nerve growth factor. Only results for BWT are presented here. RESULTS: Overall, 547 patients were randomised, 501 patients had a baseline BWT measurement, and change from baseline could be calculated for 478 patients. Mean BWT at baseline was 5.08 mm (range 2.2-11.1, SD = 1.14) and was normally distributed. A significant reduction in BWT from baseline to 12 weeks versus placebo was observed with solifenacin 5 mg (-0.42 vs. -0.16 mm, P = 0.03), but not with the 10 mg dose or with pooled solifenacin, considered the primary comparison. Both solifenacin doses were associated with improvements in efficacy and patient satisfaction endpoints versus placebo. Solifenacin was well tolerated, with dry mouth being the most common adverse event. CONCLUSIONS: There was no consistent effect of solifenacin on BWT in women with OAB/DO, despite improvements in efficacy endpoints. This study suggests that routine clinical assessment of BWT with TVUS for monitoring the effects of OAB/DO treatment is not clinically useful. Neurourol. Urodynam. 35:819-825, 2016. © 2015 Wiley Periodicals, Inc.

The efficacy and safety of irreversible electroporation for the ablation of renal masses: a prospective, human, in-vivo study protocol.

BACKGROUND: Electroporation is a novel treatment technique utilizing electric pulses, traveling between two or more electrodes, to ablate targeted tissue. The first in human studies have proven the safety of IRE for the ablation of renal masses. However the efficacy of IRE through histopathological examination of an ablated renal tumour has not yet been studied. Before progressing to a long-term IRE follow-up study it is vital to have pathological confirmation of the efficacy of the technique. Furthermore, follow-up after IRE ablation requires a validated imaging modality. The primary objectives of this study are the safety and the efficacy of IRE ablation of renal masses. The secondary objectives are the efficacy of MRI and CEUS in the imaging of ablation result. METHODS/DESIGN: 10 patients, age ≥ 18 years, presenting with a solid enhancing mass, who are candidates for radical nephrectomy will undergo IRE ablation 4 weeks prior to radical nephrectomy. MRI and CEUS imaging will be performed at baseline, one week and four weeks post IRE. After radical nephrectomy, pathological examination will be performed to evaluate IRE ablation success. DISCUSSION: The only way to truly assess short-term (4 weeks) ablation success is by histopathology of a resection specimen. In our opinion this trial will provide essential knowledge on the safety and efficacy of IRE of renal masses, guiding future research of this promising ablative technique. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT02298608 . Dutch Central Committee on Research Involving Human Subjects registration number NL44785.018.13.