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Objectives: To evaluate iceball margins after magnetic resonance (MR)-guided focal salvage prostate cryoablation and determine the correlation with local outcome., Methods: A retrospective review was performed on 47 patients that underwent percutaneous MR-guided focal cryoablation for biopsy-proven locally recurrent prostate cancer after primary radiotherapy. Preprocedural diagnostic and intraprocedural MR images were analysed to derive three-directional iceball margins. Local tumour progression after cryoablation was defined as evident tumour recurrence on follow-up MRI, positive MR-guided biopsy or biochemical failure without radiological evidence of metastatic disease., Results: Mean iceball margins were 8.9 mm (range -7.1 to 16.2), 10.1 mm (range 1.1-20.3) and 12.5 mm (range -1.5 to 22.2) in anteroposterior, left-right and craniocaudal direction respectively. Iceball margins were significantly smaller for tumours that were larger (P = .008) or located in the posterior gland (P = .047). Significantly improved local progression-free survival at 1 year post focal cryoablation was seen between patients with iceball margin >10 mm (100%), 5-10 mm (84%) and <5 mm (15%) (P < .001)., Conclusions: Iceball margins appear to correlate with local outcome following MR-guided focal salvage prostate cryoablation. Our initial data suggest that freezing should be applied at minimum 5 mm beyond the border of an MR-visible recurrent prostate tumour for successful ablation, with a wider margin appearing desirable., Key Points: • Shortest iceball margin most often occurred in anteroposterior direction • Margins were smaller in tumours that were larger or posteriorly located • Minimum iceball margin was a predictor of early local tumour progression • A minimum 5-mm margin seems required for effective cryoablation of recurrent PCa.

Interest in mechanical high intensity focused ultrasound (HIFU) ablation is rapidly growing. Boiling histotripsy (BH) is applied for mechanical fragmentation of soft tissue into submicron fragments with limited temperature increase using the shock wave and cavitation effects of HIFU. Research on BH has been largely limited to ex vivo experiments. As a consequence, the in vivo pathology after BH treatment and the relation to preexistent tissue characteristics are not well understood. This study reports on in vivo MR guided BH treatment, either with 100 or 200 pulses per focal spot, in three different subcutaneous mouse tumor models: a soft-tissue melanoma (B16OVA), a compact growing thymoma (EL4), and a highly vascularized neuroblastoma (9464D). Extensive treatment evaluation was performed using MR imaging followed by histopathology 2h after treatment. T2 weighted MRI allowed direct in vivo visualization of the BH lesions in all tumor models. The 100-pulse treated area in the B16OVA tumors was larger than the predicted treatment volume (500±10%). For the more compact growing EL4 and 9464D tumors this was 95±13% and 55±33%, respectively. Histopathology after the 100-pulse treatment revealed completely disintegrated lesions in the treated area with sharp borders in the compact EL4 and 9464D tumors, while for B16OVA tumors the lesion contained a mixture of discohesive (partly viable) clusters of cells, micro-vessel remainings, and tumor cell debris. The treatment of B16OVA with 200 pulses increased the fragmentation of tumor tissue. In all tumor types only micro-hemorrhages were detected after ablation (slightly higher after 200-pulse treatment for the highly vascularized 9464D tumors). Collagen staining revealed that the collagen fibers were to a greater or lesser extent still intact and partly clotted together near the lesion border in all tumor models. In conclusion, this study reveals effective mechanical fragmentation of different tumor types using BH without major hemorrhages. However, treatment settings may need to be adjusted to the tissue characteristics for optimal tissue fragmentation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Hepatic resection and ablative treatments, such as RFA are available treatment options for liver tumors. Advantages and disadvantages of these treatment options in patients with colorectal liver metastases need further evaluation. The purpose of this study was to systematically evaluate the role of radiofrequency ablation (RFA) compared to surgery in the curative treatment of patients with colorectal liver metastases (CRLM)., Methods: A systematic search was performed from MEDLINE, EMBASE and the Cochrane Library for studies directly comparing RFA with resection for CRLM, after which variables were evaluated., Results: RFA had significantly lower complication rates (OR = 0.44, 95% CI = 0.26-0.75, P = 0.002) compared to resection. However, RFA showed a higher rate of any recurrence (OR = 1.66, 95% CI = 1.15-2.40, P = 0.007), local recurrence (OR = 9.56, 95% CI = 6.85-13.35, P = 0.001), intrahepatic recurrence (OR = 1.96, 95% CI = 1.34-2.87, P = 0.001) and extrahepatic recurrence (OR = 1.21, 95% CI = 0.90-1.63, P = 0.22). Also, 5-year disease-free survival (OR = 2.20, 95% CI = 1.28-3.79, P = 0.005) and overall survival (OR = 2.35, 95% CI = 1.49-3.69, P = 0.001) were significantly lower in patients treated with RFA., Conclusions: RFA showed a significantly lower rate of complications, but also a lower survival and a higher rate of recurrence as compared to surgical resection. All the included studies were subject to possible patient selection bias and therefore randomized clinical trials are needed to accurately evaluate these treatment modalities., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: To assess the feasibility of percutaneous magnetic resonance (MR) imaging-guided cryoablation of small renal masses (SRMs) in a 3-T environment and to evaluate intraprocedural imaging, procedural safety, and initial outcomes., Materials and Methods: The analysis included 9 patients (4 men; median age, 72 y; range, 70-82 y) with 9 SRMs (diameter, 12-30 mm). Lesions underwent biopsy, and cryoneedles were inserted under ultrasound guidance. Verification of needle positions and ice-ball monitoring were performed by T1-weighted volumetric interpolated breath-hold examination and T2-weighted half-Fourier acquired single-shot turbo spin-echo sequences. On image analysis, needle positioning was considered appropriate if the target lesion border was visible, the needle tip was inside the target lesion, and the ice ball was expected to cover the target lesion with a 5-mm margin. If these criteria could not be assessed, imaging was considered inadequate. Technical success was defined as tumor coverage with a 5-mm margin and no residual disease on 1-mo follow-up MR imaging., Results: Median total procedure time was 170 min (range, 135-193 min). Intraoperative imaging allowed adequate needle visualization in 67% of acquired scans (4 of 7 T1-weighted and 6 of 8 T2-weighted). Appropriate positioning of two or three needles used for each procedure was confirmed in all cases on T1- or T2-weighted imaging. Ice-ball formation was adequately visualized in all patients. Technical success rate was 100%. No local recurrences were detected on follow-up imaging at a median of 12 mo (range, 3-22 mo)., Conclusions: Percutaneous MR-guided cryoablation of SRMs in a 3-T MR imaging environment is safe and feasible, showing adequate intraoperative imaging capabilities with promising short-term clinical outcomes., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

Prostate cancer is the most common cancer among men aged 50 years and older in developed countries and the third leading cause of cancer-related death in men. Multiparametric prostate MR imaging is currently the most accurate imaging modality to detect, localize, and stage prostate cancer. The role of multi-parametric MR imaging in the detection of clinically significant prostate cancer are discussed. In addition, insights are provided in imaging techniques, protocol, and interpretation.

Background: Knowledge of significant prostate (sPCa) locations being missed with magnetic resonance (MR)- and transrectal ultrasound (TRUS)-guided biopsy (Bx) may help to improve these techniques., Objective: To identify the location of sPCa lesions being missed with MR- and TRUS-Bx., Design, Setting, and Participants: In a referral center, 223 consecutive Bx-naive men with elevated prostate specific antigen level and/or abnormal digital rectal examination were included. Histopathologically-proven cancer locations, Gleason score, and tumor length were determined., Intervention: All patients underwent multi-parametric MRI and 12-core systematic TRUS-Bx. MR-Bx was performed in all patients with suspicion of PCa on multi-parametric MRI (n=142)., Outcome Measurements and Statistical Analysis: Cancer locations were compared between MR- and TRUS-Bx. Proportions were expressed as percentages, and the corresponding 95% confidence intervals were calculated., Results and Limitations: In total, 191 lesions were found in 108 patients with sPCa. From these lesion 74% (141/191) were defined as sPCa on either MR- or TRUS-Bx. MR-Bx detected 74% (105/141) of these lesions and 61% (86/141) with TRUS-Bx. TRUS-Bx detected more lesions compared with MR-Bx (140 vs 109). However, these lesions were often low risk (39%). Significant lesions missed with MR-Bx most often had involvement of dorsolateral (58%) and apical (37%) segments and missed segments with TRUS-Bx were located anteriorly (79%), anterior midprostate (50%), and anterior apex (23%)., Conclusions: Both techniques have difficulties in detecting apical lesions. MR-Bx most often missed cancer with involvement of the dorsolateral part (58%) and TRUS-Bx with involvement of the anterior part (79%)., Patient Summary: Both biopsy techniques miss cancer in specific locations within the prostate. Identification of these lesions may help to improve these techniques., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Purpose of this feasibility study was (1) to evaluate whether application of ex-vivo 7T MR of the resected tongue specimen containing squamous cell carcinoma may provide information on the resection margin status and (2) to evaluate the research and developmental issues that have to be solved for this technique to have the beneficial impact on clinical outcome that we expect: better oncologic and functional outcomes, better quality of life, and lower costs., Methods: We performed a non-blinded validation of ex-vivo 7T MR to detect the tongue squamous cell carcinoma and resection margin in 10 fresh tongue specimens using histopathology as gold standard., Results: In six of seven specimens with a histopathologically determined invasion depth of the tumor of [Formula: see text] mm, the tumor could be recognized on MR, with a resection margin within a 2 mm range as compared to histopathology. In three specimens with an invasion depth of [Formula: see text] mm, the tumor was not visible on MR. Technical limitations mainly included scan time, image resolution, and the fact that we used a less available small-bore 7T MR machine., Conclusion: Ex-vivo 7T probably will have a low negative predictive value but a high positive predictive value, meaning that in tumors thicker than a few millimeters we expect to be able to predict whether the resection margin is too small. A randomized controlled trial needs to be performed to show our hypothesis: better oncologic and functional outcomes, better quality of life, and lower costs.

Objective: Three commonly used prostate biopsy approaches are systematic transrectal ultrasound guided, direct in-bore MRI guided, and image fusion guided. The aim of this study was to calculate which strategy is most cost-effective., Materials and Methods: A decision tree and Markov model were developed to compare cost-effectiveness. Literature review and expert opinion were used as input. A strategy was deemed cost-effective if the costs of gaining one quality-adjusted life year (incremental cost-effectiveness ratio) did not exceed the willingness-to-pay threshold of €80,000 (≈$85,000 in January 2017). A base case analysis was performed to compare systematic transrectal ultrasound- and image fusion-guided biopsies. Because of a lack of appropriate literature regarding the accuracy of direct in-bore MRI-guided biopsy, a threshold analysis was performed., Results: The incremental cost-effectiveness ratio for fusion-guided biopsy compared with systematic transrectal ultrasound-guided biopsy was €1386 ($1470) per quality-adjusted life year gained, which was below the willingness-to-pay threshold and thus assumed cost-effective. If MRI findings are normal in a patient with clinically significant prostate cancer, the sensitivity of direct in-bore MRI-guided biopsy has to be at least 88.8%. If that is the case, the incremental cost-effectiveness ratio is €80,000 per quality-adjusted life year gained and thus cost-effective., Conclusion: Fusion-guided biopsy seems to be cost-effective compared with systematic transrectal ultrasound-guided biopsy. Future research is needed to determine whether direct in-bore MRI-guided biopsy is the best pathway; in this study a threshold was calculated at which it would be cost-effective.

Purpose: To correlate treatment effects of MRI-guided focal laser ablation in patients with prostate cancer with imaging using prostatectomy as standard of reference., Methods: This phase I study was approved by the Institutional Review Board. Three weeks prior to prostatectomy, five patients with histopathologically proven, low/intermediate grade prostate cancer underwent transrectal MRI-guided focal laser ablation. Per patient, only one ablation was performed to investigate the effect of ablation on the tissue rather than the effectiveness of ablation. Ablation was continuously monitored with real-time MR temperature mapping, and damage-estimation maps were computed. A post-ablation high-resolution T1-weighted contrast-enhanced sequence was acquired. Ablation volumes were contoured and measured on histopathology specimens (with a shrinkage factor of 1.15), T1-weighted contrast-enhanced images, and damage-estimation maps, and were compared., Results: A significant volume correlation was seen between the ablation zone on T1-weighted contrast-enhanced images and the whole-mount histopathology section (r = 0.94, p = 0.018). The damage-estimation maps and histopathology specimen showed a correlation of r = 0.33 (p = 0.583). On histopathology, the homogeneous necrotic area was surrounded by a reactive transition zone (1-5 mm) zone, showing neovascularisation, and an increased mitotic index, indicating increased tumor activity., Conclusions: The actual ablation zone was better indicated by T1-weighted contrast-enhanced than by damage-estimation maps. Histopathology results highlight the importance of complete tumor ablation with a safety margin.

Objectives: The aim of this study was to evaluate the technical feasibility of prostate multiparametric magnetic resonance imaging (mpMRI) at a magnetic field strength of 7 T., Materials and Methods: In this prospective institutional review board-approved study, 14 patients with biopsy-proven prostate cancer (mean age, 65.2 years; median prostate-specific antigen [PSA], 6.2 ng/mL), all providing signed informed consent, underwent 7 T mpMRI with an external 8-channel body-array transmit coil and an endorectal receive coil between September 2013 and October 2014. Image and spectral quality of high-resolution T2-weighted (T2W) imaging (0.3 × 0.3 × 2 mm), diffusion-weighted imaging (DWI; 1.4 × 1.4 × 2 mm or 1.75 × 1.75 × 2 mm), and (H) MR spectroscopic imaging (MRSI; real voxel size, 0.6 mm in 7:16 minutes) were rated on a 5-point scale by 2 radiologists and a spectroscopist., Results: Prostate mpMRI including at least 2 of 3 MR techniques was obtained at 7 T in 13 patients in 65 ± 12 minutes. Overall T2W and DWI image quality at 7 T was scored as fair (38% and 17%, respectively) to good or very good (55% and 83%, respectively). The main artifacts for T2W imaging were motion and areas of low signal-to-noise ratio, the latter possibly caused by radiofrequency field inhomogeneities. For DWI, the primary artifact was ghosting of the rectal wall in the readout direction. Magnetic resonance spectroscopic imaging quality was rated fair or good in 56% of the acquisitions and was mainly limited by lipid contamination., Conclusions: Multiparametric MRI of the prostate at 7 T is feasible at unprecedented spatial resolutions for T2W imaging and DWI and within clinically acceptable acquisition times for high-resolution MRSI, using the combination of an external 8-channel body-array transmit coil and an endorectal receive coil. The higher spatial resolutions can yield improved delineation of prostate anatomy, but the robustness of the techniques needs to be improved before clinical adoption of 7 T mpMRI.

Objectives: To assess the feasibility of a 2 nd generation MR-compatible, remote-controlled manipulator (RCM) as an aid to perform MR-guided transrectal prostate biopsy in males with suspicion of prostate cancer (PCa)., Methods: This prospective phase I study was approved by the local ethical committee and written informed consent was obtained from each patient. Twenty patients with ≥1 cancer suspicious region (CSR) with a PI-RADS score of ≥3 detected on the diagnostic multi-parametric MRI and no prior prostate treatment underwent MR-guided biopsy with the aid of the RCM. Complications were classified according to the modified Clavien system for reporting surgical complications. For evaluation of the workflow, procedure- and manipulation times were recorded., Results: All CSR's (n=20) were reachable with the MR-compatible RCM and the cancer detection rate was 70 %. The median procedure time was 36:44 minutes (range, 23 - 61 minutes) and the median manipulation time for needle guide movement was 5:48 minutes (range, 1:15 - 18:35 minutes). Two Clavien grade 1 complications were reported., Conclusions: It is feasible and safe to perform transrectal MR-guided prostate biopsy using a MR-compatible RCM as an aid. It is a fast and efficient way to biopsy suspicious prostate lesions with a minimum number of biopsies per patient., Key Points: • It is feasible to perform transrectal prostate biopsy using a MR-compatible RCM. • Using a RCM for MR-guided biopsy is safe, fast, and efficient. • All cancer suspicious regions were reachable with the RCM.

The thermal effect of high intensity focused ultrasound (HIFU) has been clinically exploited over a decade, while the mechanical HIFU is still largely confined to laboratory investigations. This is in part due to the lack of adequate imaging techniques to better understand the in-vivo pathological and immunological effects caused by the mechanical treatment. In this work, we explore the use of high frequency ultrasound (US) and photoacoustics (PA) as a potential tool to evaluate the effect of mechanical ablation in-vivo , e.g. boiling histotripsy. Two mice bearing a neuroblastoma tumor in the right leg were ablated using an MRI-HIFU system conceived for small animals and monitored using MRI thermometry. High frequency US and PA imaging were performed before and after the HIFU treatment. Afterwards, the tumor was resected for further assessment and evaluation of the ablated region using histopathology. High frequency US imaging revealed the presence of liquefied regions in the treated area together with fragmentized tissue which appeared with different reflecting proprieties compared to the surrounding tissue. Photoacoustic imaging on the other hand revealed the presence of deoxygenated blood within the tumor after the ablation due to the destruction of blood vessel network while color Doppler imaging confirmed the blood vessel network destruction within the tumor. The treated area and the presence of red blood cells detected by photoacoustics were further confirmed by the histopathology. This feasibility study demonstrates the potential of high frequency US and PA approach for assessing in-vivo the effect of mechanical HIFU tumor ablation.

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., Competing Interests: The authors declare that they have no conflict of interest.

Aim: This study compared the diagnostic capabilities of dynamic magnetic resonance defaecography (D-MRI) with conventional defaecography (CD, reference standard) in patients with symptoms of prolapse of the posterior compartment of the pelvic floor., Method: Forty-five consecutive patients underwent CD and D-MRI. Outcome measures were the presence or absence of rectocele, enterocele, intussusception, rectal prolapse and the descent of the anorectal junction on straining, measured in millimetres. Cohen's Kappa, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the positive and negative likelihood ratio of D-MRI were compared with CD. Cohen's Kappa and Pearson's correlation coefficient were calculated and regression analysis was performed to determine inter-observer agreement., Results: Forty-one patients were available for analysis. D-MRI underreported rectocele formation with a difference in prevalence (CD 77.8% vs D-MRI 55.6%), mean protrusion (26.4 vs 22.7 mm, P = 0.039) and 11 false negative results, giving a low sensitivity of 0.62 and a NPV of 0.31. For the diagnosis of enterocele, D-MRI was inferior to CD, with five false negative results, giving a low sensitivity of 0.17 and high specificity (1.0) and PPV (1.0). Nine false positive intussusceptions were seen on D-MRI with only two missed., Conclusion: The accuracy of D-MRI for diagnosing rectocele and enterocele is less than that of CD. D-MRI, however, appears superior to CD in identifying intussusception. D-MRI and CD are complementary imaging techniques in the evaluation of patients with symptoms of prolapse of the posterior compartment., (Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.)

Purpose: To assess the feasibility and accuracy of 3D ultrashort echo time (UTE) magnetic resonance (MR) thermometry of frozen tissue during cryoablation on a clinical 3T MR system., Materials and Methods: Ex vivo porcine muscle specimens (n = 4) were imaged during two cycles of 10:3 minutes freeze-thaw on a 3T clinical MR scanner. Continuous MR monitoring was performed using a 3D radial ramp-sampled UTE sequence with a shortest TE of 70 μs. Fiber optic sensors were used for temperature reference. Data of three experiments were used as reference sets. Signal intensity values were normalized to baseline before cooling and related to temperature. Data for subzero temperatures were fit to a monoexponential function. In the separate validation set, the obtained fit was used to generate 3D MR temperature maps of frozen tissue at each imaging timepoint. Statistical analysis was performed to assess accuracy of the MR temperature maps., Results: With 3D UTE imaging, MR signal was measured from frozen tissue down to temperatures as low as -40°C. Temperatures predicted from the MR temperature maps strongly correlated with sensor recorded values (r = 0.977, P < 0.001). Bland-Altman analysis demonstrated a mean difference between MR-estimated temperatures and sensor readings of -1.2 ± 2.7°C with upper and lower limits of agreement of +4.1 and -6.5°C, respectively., Conclusion: 3D MR thermometry of frozen tissue using UTE signal intensity was feasible during cryoablation on a clinical 3T MR system. Down to temperatures as low as -40°C, accuracy of the MR temperature maps was within clinically acceptable limits. J. Magn. Reson. Imaging 2016;44:1572-1579., (© 2016 International Society for Magnetic Resonance in Medicine.)

Objectives: To determine transrectal ultrasound (TRUS) visibility of magnetic resonance (MR) lesions., Methods: Data from 34 patients with 56 MR lesions and prostatectomy were used. Five observers localized and determined TRUS visibility during retrospective fusion. Visibility was correlated to Prostate Imaging-Reporting and Data System (PIRADS) and Gleason scores., Results: TRUS visibility occurred in 43% of all MR lesions and in 62% of PIRADS 5 lesions. Visible lesions had a significantly lower localization variability. On prostatectomy, 58% of the TRUS-visible lesions had a Gleason 4 or 5 component., Conclusions: Almost half of the MR lesions were visible on TRUS. TRUS-visible lesions were more aggressive than TRUS-invisible lesions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To evaluate MR-targeted TRUS prostate biopsy using a novel local reference augmentation method., Patients and Methods: Tracker-based MR-TRUS fusion was applied using local reference augmentation. In contrast to conventional whole gland fusion, local reference augmentation focuses the highest registration accuracy to the region surrounding the lesion to be biopsied. Pre-acquired multi-parametric MR images (mpMRI) were evaluated using PIRADS classification. T2-weighted MR images were imported on an ultrasound machine to allow for MR-TRUS fusion. Biopsies were targeted to the most suspicious lesion area identified on mpMRI. Each target was biopsied 1-5 times. For each biopsied lesion the diameter, PIRADS and Gleason scores, visibility during fusion, and representativeness were recorded., Results: Included were 23 consecutive patients with 25 MR suspicious lesions, of which 11 patients had a previous negative TRUS-guided biopsy and 12 were biopsy naïve. The cancer detection rate was 64 % (Gleason score ≥6). Biopsy was negative (i.e., no Gleason score) in seven patients confirmed by follow-up in all of them (up to 18 months). After MR-TRUS fusion, 88 % of the lesions could be visualized on TRUS. The cancer detection rate increases with increasing lesion size, being 73 % for lesions larger than 10 mm., Conclusion: Tracker-based MR-TRUS fusion biopsy with local reference augmentation is feasible, especially for lesions with an MR maximum diameter of at least 10 mm or PIRADS 5 lesions. If this is not the case, we recommend in-bore MR-guided biopsy.

Boiling histotripsy (BH) is a new high intensity focused ultrasound (HIFU) ablation technique to mechanically fragmentize soft tissue into submicrometer fragments. So far, ultrasound has been used for BH treatment guidance and evaluation. The in vivo histopathological effects of this treatment are largely unknown. Here, we report on an MR guided BH method to treat subcutaneous tumors in a mouse model. The treatment effects of BH were evaluated one hour and four days later with MRI and histopathology, and compared with the effects of thermal HIFU (T-HIFU). The lesions caused by BH were easily detected with T2 w imaging as a hyper-intense signal area with a hypo-intense rim. Histopathological evaluation showed that the targeted tissue was completely disintegrated and that a narrow transition zone (<200 µm) containing many apoptotic cells was present between disintegrated and vital tumor tissue. A high level of agreement was found between T2 w imaging and H&E stained sections, making T2 w imaging a suitable method for treatment evaluation during or directly after BH. After T-HIFU, contrast enhanced imaging was required for adequate detection of the ablation zone. On histopathology, an ablation zone with concentric layers was seen after T-HIFU. In line with histopathology, contrast enhanced MRI revealed that after BH or T-HIFU perfusion within the lesion was absent, while after BH in the transition zone some micro-hemorrhaging appeared. Four days after BH, the transition zone with apoptotic cells was histologically no longer detectable, corresponding to the absence of a hypo-intense rim around the lesion in T2 w images. This study demonstrates the first results of in vivo BH on mouse tumor using MRI for treatment guidance and evaluation and opens the way for more detailed investigation of the in vivo effects of BH. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

A diagnostic dilemma exists in cases wherein a patient with clinical suspicion for prostate cancer has a negative transrectal ultrasound-guided biopsy session. Although transrectal ultrasound-guided biopsy is the standard of care, a paradigm shift is being observed. In biopsy-naive patients and patients with at least 1 negative biopsy session, multiparametric magnetic resonance imaging (MRI) is being utilized for tumor detection and subsequent targeting. Several commercial devices are now available for targeted prostate biopsy ranging from transrectal ultrasound-MR fusion biopsy to in bore MR-guided biopsy. In this review, we will give an update on the current status of in-bore MRI-guided biopsy systems and discuss value of prostate imaging-reporting and data system (PIRADS).

Objectives: To compare translabial three-dimensional (3D) ultrasound with magnetic resonance imaging (MRI) for the measurement of levator hiatal biometry at rest in women with pelvic organ prolapse, and to determine the interobserver reliability between two independent observers for ultrasound and MRI measurements., Methods: Data were derived from a multicenter prospective cohort study in which women scheduled for conventional anterior colporrhaphy underwent translabial 3D ultrasound and MRI prior to surgery. Intraclass correlation coefficients (ICCs) were calculated to estimate interobserver reliability between two independent observers and determine the agreement between ultrasound and MRI measurements. Bland-Altman plots were created to assess the agreement between ultrasound and MRI measurements., Results: Data from 139 women from nine hospitals were included in the study. The interobserver reliability of ultrasound assessment at rest, during Valsalva maneuver and during contraction and of MRI assessment at rest were moderate or good. The agreement between ultrasound and MRI for the measurement of levator hiatal biometry at rest was moderate, with ICCs of 0.52 (95%CI, 0.32-0.66) for levator hiatal area, 0.44 (95%CI, 0.21-0.60) for anteroposterior diameter and 0.44 (95%CI, 0.22-0.60) for transverse diameter. Levator hiatal biometry measurements were statistically significantly larger on MRI than on translabial 3D ultrasound., Conclusions: The agreement between translabial 3D ultrasound and MRI for measurement of the levator hiatus at rest in women with pelvic organ prolapse was only moderate. The results of translabial 3D ultrasound and MRI should therefore not be used interchangeably in daily practice or in clinical research. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Unlabelled: Most prostate cancers (PC) are currently found on the basis of an elevated PSA, although this biomarker has only moderate accuracy. Histological confirmation is traditionally obtained by random transrectal ultrasound guided biopsy, but this approach may underestimate PC. It is generally accepted that a clinically significant PC requires treatment, but in case of an non-significant PC, deferment of treatment and inclusion in an active surveillance program is a valid option. The implementation of multiparametric magnetic resonance imaging (mpMRI) into a screening program may reduce the risk of overdetection of non-significant PC and improve the early detection of clinically significant PC. A mpMRI consists of T2-weighted images supplemented with diffusion-weighted imaging, dynamic contrast enhanced imaging, and/or magnetic resonance spectroscopic imaging and is preferably performed and reported according to the uniform quality standards of the Prostate Imaging Reporting and Data System (PIRADS). International guidelines currently recommend mpMRI in patients with persistently rising PSA and previous negative biopsies, but mpMRI may also be used before first biopsy to improve the biopsy yield by targeting suspicious lesions or to assist in the selection of low-risk patients in whom consideration could be given for surveillance., Teaching Points: • MpMRI may be used to detect or exclude significant prostate cancer. • MpMRI can guide targeted rebiopsy in patients with previous negative biopsies. • In patients with negative mpMRI consideration could be given for surveillance. • MpMRI may add valuable information for the optimal treatment selection.

Purpose: The combination of resection and radiofrequency ablation (RFA) may provide an alternative treatment for patients with unresectable colorectal liver metastases (CRLM). Although the results in literature look promising, uncertainty exists with regard to complication risks and survival for this therapy., Methods: From January 2000 to May 2013, patients were included in a prospective multicenter database when treated for CRLM. Exclusion criteria were: two-staged treatment, synchronous resection of liver metastases and primary tumor, loss to follow-up or extrahepatic metastases. Patients were divided in a resection-only group (ROG) and combination group (CG). Outcome variables were retrospectively analyzed., Results: In CG, 98 patients were included versus 534 patients in ROG. There were no differences in general patient characteristics. Patients in CG had a higher Fong clinical risk score (CRS; P = 0.001), better ASA classification (P = 0.04) and received more neoadjuvant chemotherapy (P = 0.001). There was no difference in postoperative morbidity or 90-day mortality. The 5-year disease-free survival (DFS) for CG and ROG was 25% and 36.1% (P = 0.03), respectively. For the 5-year overall survival (OS) this was respectively 42% and 62.2% (P = 0.001). On multivariate analysis, Fong CRS was a significant predictor for DFS. For OS, Fong CRS, ASA class IV and the combination therapy were significant predictors., Conclusion: The combination of hepatic resection and intraoperative RFA is a safe procedure, without increase in postoperative morbidity or mortality. Combining RFA and resection in one session is a valid treatment option for patients who would otherwise be inoperable., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Unlabelled: From April 2013 to July 2014, 25 consecutive men participated in a longitudinal outcomes study following in-bore magnetic resonance imaging (MRI)-guided focal laser ablation (FLA) of prostate cancer (PCa). Eligibility criteria were clinical stage T1c and T2a disease; prostate-specific antigen (PSA) <10 ng/ml; Gleason score <8; and cancer-suspicious regions (CSRs) on multiparametric MRI harboring PCa. CSRs harboring PCa were ablated using a Visualase cooled laser applicator system. Tissue temperature was monitored throughout the ablation cycle by proton resonance frequency shift magnetic resonance thermometry from phase-sensitive images. There were no significant differences between baseline and 3-mo mean American Urological Association Symptom Score or Sexual Health Inventory in Men scores. No man required pads at any time. Overall, the mean PSA decrease between baseline and 3 mo was 2.3 ng/ml (44.2%). Of 28 sites subjected to target biopsy after FLA, 26 (96%) showed no evidence of PCa. Our study provides encouraging evidence that excellent early oncologic control of significant PCa can be achieved following FLA, with virtually no complications or adverse impact on quality of life. Longer follow-up is required to show that oncologic control is durable., Patient Summary: Early results for focal laser ablation of prostate cancer are very encouraging. Until long-term oncologic control is demonstrated, focal laser ablation must be considered an investigational treatment option., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Detection of clinically significant prostate cancer (PCa) is a major challenge. It has been shown that multiparametric magnetic resonance imaging (mpMRI) facilitates localisation of PCa and can help in targeting prostate biopsy., Objective: To systematically review the literature to determine the diagnostic accuracy of mpMRI in the detection of clinically significant PCa., Evidence Acquisition: The Pubmed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from January 1, 2000 to September 30, 2014, using the search criteria "prostate OR Pca OR PSA OR prostatic OR prostate cancer" AND "MR OR NMR OR NMRI OR MRI OR magnetic resonance OR ADC OR DWI OR DCE OR diffusion weighted OR dynamic contrast OR multiparametric OR MRSI OR MR spectroscopy". Two reviewers independently assessed 1729 records. Two independent reviewers assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) 2 tool., Evidence Synthesis: Twelve articles were eventually selected. Patients had a median age of 62-65 yr (range 39-83 yr), a median prostate-specific antigen (PSA) level of 5.1-13.4 ng/ml (range 1.2-228 ng/ml), and Gleason score of 6-10. Various definitions of clinical significance were used, mainly based on maximum cancer core length and grade at biopsy, number of positive cores, and PSA. Detection of clinically significant PCa using mpMRI ranged from 44% to 87% in biopsy-naïve males and men with prior negative biopsies using prostate biopsy or definitive pathology of a radical prostatectomy specimen as the reference standard. The negative predictive value for exclusion of significant disease ranged from 63% to 98%., Conclusions: mpMRI is able to detect significant PCa in biopsy-naïve males and men with prior negative biopsies. The negative predictive value of mpMRI is important to the clinician because mpMRI could be used to rule out significant disease. This may result in fewer or no systematic or targeted biopsies in patients with PSA suspicious for prostate cancer., Patient Summary: We reviewed the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) for the detection of clinically significant prostate cancer (PCa). We conclude that mpMRI is able to detect significant PCa and may used to target prostate biopsies., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction and Hypothesis: Defecatory complaints have a severe impact on quality of life. The additional value of pelvic floor MRI in patients with defecatory complaints is unclear. Our aim was to correlate the presence of defects and atrophy of the anal sphincter complex using pelvic floor MRI in women with mixed pelvic floor symptoms and to establish patient characteristics and self reported complaints predictive of pathology., Methods: This is a retrospective study among women with mixed pelvic floor symptoms who underwent external phased-array MRI and completed a questionnaire on bothersome defecatory complaints. Data on patient characteristics, including obstetrical history and questionnaire scores were correlated with the assessment of anal sphincter defects and atrophy on pelvic floor MRI., Results: One hundred and fifty-eight women were included. A defect of the external anal sphincter (EAS) and internal anal sphincter (IAS) was found in 18 (11%) and 5 (3%) patients respectively. Atrophy of the EAS was present in 72 patients (46%), with more cases of mild (n = 52, 33%) than severe atrophy (n = 20, 13%). The variable "previous third or fourth degree tear" had a significant positive association with an IAS defect on MRI, with an OR of 9.533 (1.425-63.776). Patients with EAS atrophy had higher scores for fecal incontinence (indicating more bother) than patients without EAS atrophy. Higher age and BMI were true predictors of the presence of more severe EAS atrophy., Conclusion: Atrophy of the EAS was highly prevalent in this population and was associated with bothersome symptoms of fecal incontinence.

Aim: To gain greater insight into the biological mechanisms occurring shortly after discontinuation of VEGFR TKIs treatment because of progressive disease (PD)., Patients and Methods: Sixteen patients with PD during treatment with sorafenib or sunitinib were randomized to either directly stop the VEGFR TKI or to continue for another two weeks. At baseline (i.e. at the moment of PD) and after two weeks FDG-PET/CT, functional-MRI and blood biomarkers of disease were evaluated., Results: A statistically significant difference in median change from baseline to two weeks later in K(trans) and LDH levels was observed between patients who directly stopped versus those who continued treatment (1.6 s(-1) versus -1.1s(-1), p=0.03; -73.0 U/L versus 52.0 U/L, p=0.008; respectively). There were no further differences between groups., Conclusion: Two weeks after discontinuation of VEGFR TKIs in mRCC because of PD, a rise in K(trans) accompanied by a decrease in LDH indicates an increase in tumor vascularization. This implies that at the moment of PD the effect of VEGFR TKIs is not completely exhausted., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Introduction: Focal therapy can offer the middle ground for treatment between active surveillance and radical therapy in patients with low- and intermediate-risk prostate cancer. Factors that prohibit focal therapy from being standard of care are numerous. Several consensus projects have been conducted to position the utilization of imaging and trial design in focal therapy. However, the literature is still scarce on patient follow-up after focal therapy. For these reasons, an international multidisciplinary consensus project was established in order to reach consensus about a uniform follow-up protocol after focal therapy., Objective: To standardize patient follow-up after focal therapy., Materials and Methods: A literature study was performed, and a questionnaire was constructed. The questionnaire was sent out to 76 participants (70 % urologists, 28 % radiologists and 2 % biomedical engineers) in three consecutive rounds according to the Delphi method. In each round, the panelists were presented with the results of the previous round. Participants each had the opportunity to adapt, delete or add questions. The topics discussed pertaining to follow-up after focal therapy were as follows: (1) general,(2) biopsies, (3) PSA, (4) digital rectal examination (DRE), (5) imaging, (6) quality of life (QoL) and (7) registration and pooling of data. The project was concluded with a face-to-face meeting in which final conclusions were formulated., Results: The follow-up after focal therapy should be a minimum of 5 years. The following modalities should be included in assessing post-treatment outcomes: multiparametric MRI (mpMRI), biopsies, assessment of erectile function, QoL, urinary symptoms and incontinence. A systematic 12-core TRUS biopsy combined with 4-6 targeted biopsy cores of the treated area and any suspicious lesion(s) should be performed after 1 year, and thereafter only when there is suspicion on imaging. The ideal way to perform targeted biopsies is to use TRUS-MRI fusion technology. PSA should be performed for research purposes, in the first year, every 3 months, and after the first year, every 6 months. mpMRI is the optimal imaging modality for follow-up after focal therapy. On a 1.5T scanner, an endorectal coil is strongly advised by the panel, whereas on a 3T machine, it is optional, however, it will improve image quality. The following sequences should be included: T2WI, DWI including high b values of >1,000 and ADC maps of DWI, DCE and T1WI. Imaging should be performed at 6 months and at 1 year following treatment; after the first year post-treatment, it should be performed every year until 5 years following treatment. All data should ideally be pooled in a common global database., Conclusion: Focal therapy is a relatively new form of treatment for prostate cancer. In order to include focal therapy as a standard of care treatment, consistent follow-up is necessary. By implementing the results of this consensus study, focal therapy users will be able to provide important and standardized outcome data.

Context: Debates on overdiagnosis and overtreatment of prostate cancer (PCa) are ongoing and there is still huge uncertainty regarding misclassification of prostate biopsy results. Several imaging techniques that have emerged in recent years could overcome over- and underdiagnosis in PCa., Objective: To review the literature on transrectal ultrasound (TRUS)-based techniques (contrast enhancement, HistoScanning, elastography) and magnetic resonance imaging (MRI)-based techniques for a nonsystematic overview of their benefits and limitations., Evidence Acquisition: A comprehensive search of the PubMed database between August 2004 and August 2014 was performed. Studies assessing grayscale TRUS, contrast-enhanced (CE)-TRUS, elastography, HistoScanning, multiparametric MRI (mpMRI), and MRI-TRUS fusion biopsy were included. Publications before 2004 were included if they reported the principle or the first clinical results for these techniques., Evidence Synthesis: Grayscale TRUS alone cannot detect PCa foci (detection rate 23-29%). TRUS-based (elastography) and MRI-based techniques (MRI-TRUS fusion biopsy) have significantly improved PCa diagnostics, with sensitivity of 53-74% and specificity of 72-95%. HistoScanning does not provide convincing or homogeneous results (specificity 19-82%). CE-TRUS seems to be user dependent; it is used in a low number of high-volume centers and has wide ranges for sensitivity (54-79%) and specificity (42-95%). For all the techniques reviewed, prospective multicenter studies with consistent definitions are lacking., Conclusions: Standard grayscale TRUS is unreliable for PCa detection. Among the techniques reviewed, mpMRI and MRI-TRUS fusion biopsy seem to be suitable for enhancing PCa diagnostics. Elastography shows promising results according to the literature. CE-TRUS yields very inhomogeneous results and might not be the ideal technique for clinical practice. The value of HistoScanning must be questioned according to the literature., Patient Summary: New imaging modalities such as elastography and magnetic resonance imaging/transrectal ultrasound fusion biopsies have improved the detection of prostate cancer. This may lower the burden of overtreatment as a result of more precise diagnosis., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

This article reviews recent and ongoing developments in multiparametric magnetic resonance imaging (mpMRI) of the prostate. Advances in T2-weighted imaging, diffusion-weighted imaging, dynamic contrast-enhanced imaging, and spectroscopic imaging are described along with advances related to radiofrequency coils and imaging at high magnetic field. As mpMRI is increasingly becoming routine in various aspects of clinical prostate cancer management, its role in detection, localization, staging, assessment of aggressiveness, and active surveillance is discussed. Combined with growing clinical adoption of the techniques already at hand, continual optimization of acquisition techniques and image interpretation schemes will further strengthen the role of mpMRI as an important diagnostic test in prostate cancer management.

Background: Thermal and mechanical high intensity focused ultrasound (HIFU) ablation techniques are in development for non-invasive treatment of cancer. However, knowledge of in vivo histopathologic and immunologic reactions after HIFU ablation is still limited. This study aims to create a setup for evaluation of different HIFU ablation methods in mouse tumors using high-field magnetic resonance (MR) guidance. An optimized MR-guided-HIFU setup could be used to increase knowledge of the different pathologic and immunologic reactions to different HIFU ablation methods., Methods: Three different HIFU treatment strategies were applied in mouse melanomas (B16): a thermal (continuous wave), a mechanical (5 ms pulsed wave), and an intermediate setting (20 ms pulsed wave) for HIFU ablation, all under MR guidance using a 7 tesla animal MR system. Histopathologic evaluation was performed 3 days after treatment., Results: The focus of the ultrasound transducer could accurately be positioned within the tumor under MR image guidance, without substantial damage to the surrounding tissue and skin. All mice retained complete use of the treated leg after treatment. Temperatures of >60, <50, and <44 °C were reached during thermal, intermediate, and mechanical HIFU ablation, respectively. Thermal-treated tumors showed large regions of coagulative necrosis. Tumors of both the mechanical and intermediate groups showed fractionated tissue with islands of necrosis and some pseudocysts with hemorrhage., Conclusion: A stable small animal MR-guided HIFU setup was designed and evaluated for follow-up MR imaging and histopathologic responses of the treated tumors. This will facilitate further studies with a larger number of mice for detailed evaluation of the pathologic and immunologic response to different HIFU strategies.

Background: Mucinous carcinoma (MC) is a distinct form of rectal cancer (RC) comprising 10 % of all cases and has been associated with an impaired prognosis compared with non-mucinous adenocarcinoma (AC). The benefit of today's modern treatment for MC patients is unknown but a prospective randomized trial to answer this does not seem feasible. This study provides an analysis of the modern treatment of rectal MC and efficacy of preoperative therapies for MC patients., Methods: Data from three large (trial) cohorts were used. Data from the Netherlands Cancer Registry (NCR) were used to analyze the prognosis of RC patients over time (N = 38,035). To study the benefit of preoperative short-term radiotherapy, patients from the total mesorectal excision (TME) trial (N = 1,530) were selected, and the benefit from preoperative chemoradiotherapy was analyzed with data on 540 locally advanced RC (LARC) patients from two hospitals., Results: Data from the NCR confirmed that 5-year overall survival for MC was significantly worse from 1989 to 1998, but no longer different from AC from 1999 onwards. MC patients had a higher rate of positive circumferential resection margin than AC patients (TME trial 27.2 vs. 16.5 %, p = 0.006; LARC cohort 34.5 vs. 9.8 %, p < 0.0001), but there was no difference in outcome between MC and AC patients after preoperative short-term radiotherapy or chemoradiotherapy., Conclusions: Modern treatment of RC has benefited MC patients, leading to equal survival for MC and AC patients. Enhancements in the fields of imaging and quality of surgery have improved outcome and preoperative therapies should be recommended for both histological subtypes.

Objective: The purpose of this article is to identify histopathologically proven prostate cancer locations using MRI followed by MRI-guided biopsy in patients with elevated prostate-specific antigen (PSA) levels and at least one negative transrectal ultrasound (TRUS)-guided biopsy session. Our hypothesis is that in this patient group most cancers are located in the anterior portion of the prostate. This may have implications for the biopsy strategy regarding the location of sampling., Materials and Methods: This retrospective study consisted of 872 consecutive men who had undergone MRI-guided prostate biopsy. Inclusion criteria were PSA level greater than or equal to 4 ng/mL, one or more negative TRUS-guided biopsy session, the presence of suspicious lesions on previous multiparametric MRI, and prostate cancer histopathologically proven by MRI-guided biopsy. Thereafter, the location of intermediate- or high-risk cancers and cancers with a maximum cancer core length of 6 mm or longer were determined. The proportion of cancer locations was compared using a chi-square test. One-way ANOVA analyses were performed to compare patient characteristics., Results: Results were presented on both a patient and lesion basis because a single patient can have multiple lesions. In total, 176 of 872 patients met the inclusion criteria. Prostate cancer was detected in 202 of 277 (73%) suspicious lesions. In total, 76% of patients had cancer of the transition zone and anterior fibromuscular stroma. Peripheral zone cancers were found in 30% of the patients, and 6% had cancers in both zones. In 70% of cases (141/202; 95%, CI, 63-76%), lesions were located anteriorly; this included 75% (132/176; 95%, CI, 69-81%) of patients. Intermediate- or high-risk prostate cancer was found in 93% (128/138; 95%, CI, 88-96%) of patients. Of these patients, 73% (94/128; 95%, CI, 66-81%) had anterior involvement. Cancers with a maximum cancer core length of 6 mm or more were more likely to be located in the anterior part of the prostate than were cancers with a core length of less than 6 mm (66% vs 6%). Most cancers 58% (102/176; 95% CI, 51-65%) were found in the mid prostate. Anterior involvement of prostate cancer detected by MRI-guided biopsy was statistically significantly (p = 0.04) higher in patients with two or more negative TRUS-guided biopsy sessions (79%) than in those with one negative TRUS-guided biopsy session (55%)., Conclusion: Anterior involvement was high (76%) in patients with an elevated PSA level and one or more negative TRUS-guided biopsy session, and the majority of these cancers (93%) were intermediate or high risk.

Background: The multiple pathways that are involved in neuroendocrine differentiation (NED) in prostate cancer (PCa) are poorly elucidated. Evidence suggests that several environmental triggers induce NED leading to the adaptation of PCa to its close environment to maintain cell proliferation. Nevertheless, there is conflicting evidence regarding the prognostic role of NED in PCa., Methods: In this review, we aimed to summarize all available data about NED and to assess the prognostic role of NED in disease progression and therapy resistance, and its role in routine clinical practice. This review was based on articles found through a PubMed literature search between 1993 and 2013. The study outcome measure was the effect of NED on oncologic outcomes at each PCa stage., Results: In total, 59 articles reporting on the effect of NED on oncologic outcomes have been selected. In clinical practice, immunostaining for NED markers could have interesting predictive value for assessing the oncologic outcomes in patients receiving androgen-deprivation therapy. Thus, patients with high NED burden may be candidates for more aggressive treatment strategies targeting NED pathways. Conversely, strong evidence is lacking concerning its potential independent prognostic value in hormone-naïve PCa., Conclusions: Current published data are not sufficient to recommend the use of NE markers in routine practice, particularly at early PCa stage., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The best known method of high-intensity focused ultrasound is thermal ablation, but interest in non-thermal, mechanical destruction is increasing. The advantages of mechanical ablation are that thermal protein denaturation remains limited and less damage is created to the surrounding tissue by thermal diffusion. The two main techniques for mechanical fragmentation of tissue are histotripsy and boiling histotripsy. These techniques can be used for complete liquefaction of tumor tissue into submicron fragments, after which the fragmented tissue can be easily removed by natural (immunologic) responses. Interestingly it seems that there is a correlation between the degree of destruction and tissue specific characteristics based on the treatment settings used. In this review article, the technical aspects of these two techniques are described, and an overview of the in vivo pathologic and immunologic responses is provided., (Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the oncologic benefit or otherwise of local treatment of the prostate in patients with primary metastatic prostate cancer., Methods: A review of the literature was performed in April 2014 using the Medline/PubMed database. Studies were identified using the search terms "prostate cancer," "metastatic," "metastasis," "high risk," "radiation therapy," "radiotherapy" and "prostatectomy" from 1990 until April, 2014. Articles were also identified through searches of references of these articles., Results: Retrospective series and population-based data suggest that the use of local treatment of the prostate in patients with primary metastatic prostate cancer may improve cancer-specific survival and overall survival compared with treating these patients with androgen deprivation therapy alone. The clinical outcome in metastatic prostate cancer is largely determined by the extent of lymph node involvement and overall metastatic burden. Contemporary data are lacking to recommend one alternative of local therapy (radiotherapy or radical prostatectomy) over the other. The primary limitation of this literature review is the lack of published randomized trial assessing the role of local treatment in addition to systemic therapy., Conclusions: Local treatment appears to improve oncologic outcomes in metastatic prostate cancer patients. Nevertheless, due to the lack of high-quality evidence, its role needs to be confirmed in future prospective trials. The selection of ideal candidates and optimal treatment alternative (radiotherapy, radical prostatectomy or other) warrants further investigation.

Objective: To explore preferences in the management of patients with newly diagnosed high-risk prostate cancer (PCa) among urologists in Europe through a web-based survey., Materials and Methods: A web-based survey was conducted between 15 August and 15 September 2013 by members of the Prostate Cancer Working Group of the Young Academic Urologists Working Party of the European Association of Urology (EAU). A specific, 29-item multiple-choice questionnaire covering the whole spectrum of diagnosis, staging and treatment of high-risk PCa was e-mailed to all urologists included in the mailing list of EAU members. Europe was divided into four geographical regions: Central-Eastern Europe (CEE), Northern Europe (NE), Southern Europe (SE) and Western Europe (WE). Descriptive statistics were used. Differences among sample segments were obtained from a z-test compared with the total sample., Results: Of the 12,850 invited EAU members, 585 urologists practising in Europe completed the survey. High-risk PCa was defined as serum PSA ≥20 ng/mL or clinical stage ≥ T3 or biopsy Gleason score ≥ 8 by 67% of responders, without significant geographical variations. The preferred single-imaging examinations for staging were bone scan (74%, 81% in WE and 70% in SE; P = 0.02 for both), magnetic resonance imaging (53%, 72% in WE and 40% in SE; P = 0.02 and P = 0.01, respectively) and computed tomography (45%, 60% in SE and 23% in WE; P = 0.01 for both). Pre-treatment predictive tools were routinely used by 62% of the urologists, without significant geographical variations. The preferred treatment was radical prostatectomy as the initial step of a multiple-treatment approach (60%, 40% in NE and 70% in CEE; P = 0.02 and P < 0.01, respectively), followed by external beam radiation therapy with androgen deprivation therapy (29%, 45% in NE and 20% in CEE; P = 0.01 and P = 0.02, respectively), and radical prostatectomy as monotherapy (4%, 7% in WE; P = 0.04). When surgery was performed, the open retropubic approach was the most popular (58%, 74% in CEE, 37% in NE; P < 0.01 for both). Pelvic lymph node dissection was performed by 96% of urologists, equally split between a standard and extended template. There was no consensus on the definition of disease recurrence after primary treatment, and much heterogeneity in the administration of adjuvant and salvage treatments., Conclusion: With the limitation of a low response rate, the present study is the first survey evaluating preferences in the management of high-risk PCa among urologists in Europe. Although the definition of high-risk PCa was fairly uniform, wide variations in patterns of primary and adjuvant/salvage treatments were observed. These differences might translate into variations in quality of care with a possible impact on ultimate oncological outcome., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objectives: Prostate biopsy (PB) is the gold standard for the diagnosis of prostate cancer (PCa). However, the optimal number of biopsy cores remains debatable. We sought to compare contemporary standard (10-12 cores) vs. saturation (=18 cores) schemes on initial as well as repeat PB., Methods: A non-systematic review of the literature was performed from 2000 through 2013. Studies of highest evidence (randomized controlled trials, prospective non-randomized studies, and retrospective reports of high quality) comparing standard vs saturation schemes on initial and repeat PB were evaluated. Outcome measures were overall PCa detection rate, detection rate of insignificant PCa, and procedure-associated morbidity., Results: On initial PB, there is growing evidence that a saturation scheme is associated with a higher PCa detection rate compared to a standard one in men with lower PSA levels (<10 ng/ml), larger prostates (>40 cc), or lower PSA density values (<0.25 ng/ml/cc). However, these cut-offs are not uniform and differ among studies. Detection rates of insignificant PCa do not differ in a significant fashion between standard and saturation biopsies. On repeat PB, PCa detection rate is likewise higher with saturation protocols. Estimates of insignificant PCa vary widely due to differing definitions of insignificant disease. However, the rates of insignificant PCa appear to be comparable for the schemes in patients with only one prior negative biopsy, while saturation biopsy seems to detect more cases of insignificant PCa compared to standard biopsy in men with two or more prior negative biopsies. Very extensive sampling is associated with a high rate of acute urinary retention, whereas other severe adverse events, such as sepsis, appear not to occur more frequently with saturation schemes., Discussion: Current evidence suggests that saturation schemes are associated with a higher PCa detection rate compared to standard ones on initial PB in men with lower PSA levels or larger prostates, and on repeat PB. Since most data are derived from retrospective studies, other endpoints such as detection rate of insignificant disease - especially on repeat PB - show broad variations throughout the literature and must, thus, be interpreted with caution. Future prospective controlled trials should be conducted to compare extended templates with newer techniques, such as image-guided sampling, in order to optimize PCa diagnostic strategy.

Background: The use of multiparametric magnetic resonance imaging (mpMRI) to detect and localize prostate cancer has increased in recent years. In 2010, the European Society of Urogenital Radiology (ESUR) published guidelines for mpMRI and introduced the Prostate Imaging Reporting and Data System (PI-RADS) for scoring the different parameters., Purpose: To evaluate the reliability and diagnostic performance of endorectal 1.5-T mpMRI using the PI-RADS to localize the index tumor of prostate cancer in patients undergoing prostatectomy., Material and Methods: This institutional review board IRB-approved, retrospective study included 63 patients (mean age, 60.7 years, median PSA, 8.0). Three observers read mpMRI parameters (T2W, DWI, and DCE) using the PI-RADS, which were compared with the results from whole-mount histopathology that analyzed 27 regions of interest. Inter-observer agreement was calculated as well as sensitivity, specificity, positive predictive value (PPV), and negative predicted value (NPV) by dichotomizing the PI-RADS criteria scores ≥3. A receiver-operating curve (ROC) analysis was performed for the different MR parameters and overall score., Results: Inter-observer agreement on the overall score was 0.41. The overall score in the peripheral zone achieved sensitivities of 0.41, 0.60, and 0.55 with an NPV of 0.80, 0.84, and 0.83, and in the transitional zone, sensitivities of 0.26, 0.15, and 0.19 with an NPV of 0.92, 0.91, and 0.92 for Observers 1, 2, and 3, respectively. The ROC analysis showed a significantly increased area under the curve (AUC) for the overall score when compared to T2W alone for two of the three observers., Conclusion: 1.5 T mpMRI using the PI-RADS to localize the index tumor achieved moderate reliability and diagnostic performance., (© The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Objective: To assess the diagnostic performance of translabial three-dimensional ultrasonography in detecting major levator ani defects in women with pelvic organ prolapse compared with magnetic resonance imaging (MRI) and to assess the interobserver agreement in detecting levator ani defects with translabial three-dimensional ultrasonography., Methods: In a multicenter cohort study, 140 women indicated for primary surgery of pelvic organ prolapse quantification stage II or more cystocele were included. Patients undergoing mesh surgery or concomitant stress incontinence surgery were excluded. All consenting patients underwent translabial three-dimensional ultrasonography and MRI of the pelvic floor before surgery. Two observers (out of a pool of four observers) assessed translabial three-dimensional ultrasound images; two other observers (out a pool of five observers) assessed MRIs for levator ani muscle damage. In case of disagreement, the images were discussed in a consensus meeting., Results: Of the 135 scans, 45 major levator ani defects were detected on ultrasonogram (33.3%) and 32 were confirmed at MRI (23.7%). Of the 41 major levator ani defects detected on MRI, nine were missed at translabial three-dimensional ultrasonogram. Sensitivity was 0.78 (32 of 41) (95% confidence interval [CI] 0.65-0.91) and specificity was 0.86 (81 of 94) (95% CI 0.79-0.93) in detecting major levator ani defects with translabial three-dimensional ultrasonography compared with MRI. There was good agreement scoring levator ani defects on translabial three-dimensional ultrasonography, with a κ of 0.67 (95% CI 0.58-0.76); agreement in recognizing major levator ani defects was moderate, with a κ of 0.53 (95% CI 0.37-0.69)., Conclusion: Translabial three-dimensional ultrasonography shows reasonable agreement with MRI in detecting major levator defects. Because of the moderate interobserver agreement, it will be difficult to implement ultrasonography in daily practice., Clinical Trial Registration: Netherlands Trial Register, www.trialregister.nl, NTR2220.

Purpose: To assess the feasibility of automatic needle-guide tracking by using a real-time phase-only cross correlation ( POCC phase-only cross correlation ) algorithm-based sequence for transrectal 3-T in-bore magnetic resonance (MR)-guided prostate biopsies., Materials and Methods: This study was approved by the ethics review board, and written informed consent was obtained from all patients. Eleven patients with a prostate-specific antigen level of at least 4 ng/mL (4 μg/L) and at least one transrectal ultrasonography-guided biopsy session with negative findings were enrolled. Regions suspicious for cancer were identified on 3-T multiparametric MR images. During a subsequent MR-guided biopsy, the regions suspicious for cancer were reidentified and targeted by using the POCC phase-only cross correlation -based tracking sequence. Besides testing a general technical feasibility of the biopsy procedure by using the POCC phase-only cross correlation -based tracking sequence, the procedure times were measured, and a pathologic analysis of the biopsy cores was performed., Results: Thirty-eight core samples were obtained from 25 regions suspicious for cancer. It was technically feasible to perform the POCC phase-only cross correlation -based biopsies in all regions suspicious for cancer in each patient, with adequate biopsy samples obtained with each biopsy attempt. The median size of the region suspicious for cancer was 8 mm (range, 4-13 mm). In each region suspicious for cancer (median number per patient, two; range, 1-4), a median of one core sample per region was obtained (range, 1-3). The median time for guidance per target was 1.5 minutes (range, 0.7-5 minutes). Nineteen of 38 core biopsy samples contained cancer., Conclusion: This study shows that it is feasible to perform transrectal 3-T MR-guided biopsies by using a POCC phase-only cross correlation algorithm-based real-time tracking sequence., (© RSNA, 2014.)

Purpose: To correlate T1-weighted (T1w) magnetic resonance (MR) image contrast around a cryoablation iceball with temperature in a phantom study and to compare this to its in vivo appearance during MR-guided focal cryoablation of prostate cancer., Methods: A MR-compatible cryoneedle was inserted into identical gel phantoms (n = 3) on a 1.5 T MR system. Two fiber-optic temperature sensors were placed parallel to the needle. A fast 3D T1w gradient echo (GRE) sequence (TR/TE/FA = 4.81/1.98/6°) was used to monitor iceball progression. Normalized signal intensity (SI) was correlated with temperature. The same T1w sequence was used during MR-guided prostate cryoablation in ten consecutive patients at the authors' institution. In vivo findings were quantitatively compared to the phantom data., Results: In the phantom study, the cryoablation iceball appeared in the T1w MR images as a sharply delineated signal void. A 2.2 ± 0.2 mm wide hyperintense rim directly surrounded the iceball at cooled but nonfreezing temperatures (<20 °C) in the gel. Normalized SI was maximum at 8.4 ± 2.4 °C, showing a 35.6%-43.0% (mean 40.5%) increase with respect to baseline before cooling. In the clinical procedures, the same image contrast was observed in vivo in all patients. In vivo, width of the hyperintense rim was 1.6 ± 0.6 mm. Normalized SI increases with respect to nontreated prostate ranged 28.4%-55.6% (mean 36.8%). On quantitative analysis, normalized SI changes along a linear region of interest from surrounding tissue onto the iceball center were similar between the patients and phantom setting (root mean square difference 0.06)., Conclusions: The hyperintense rim around the iceball in fast T1w GRE images corresponded to cooled but nonfreezing temperatures (<20 °C) proximal to the frozen zone. The same image contrast was observed both in a phantom study as well as in vivo in the human prostate during cryotherapy. Potentially, monitoring of this rim could be useful in order to maintain a safe margin from at-risk tissues during MR-guided prostate cryoablation procedures.

Laser interstitial thermotherapy (LITT) is a relatively new focal therapy technique for the ablation of localized prostate cancer. In this study, for the first time, we are integrating ex vivo pathology and magnetic resonance imaging (MRI) to assess the imaging characteristics of prostate cancer and treatment changes following LITT. Via a unique clinical trial, which gave us the availability of ex vivo histology and pre- and post-LITT MRIs, (1) we investigated the imaging characteristics of treatment effects and residual disease, and (2) evaluated treatment-induced feature changes in the ablated area relative to the residual disease. First, a pathologist annotated the ablated area and the residual disease on the ex vivo histology. Subsequently, we transferred the annotations to the post-LITT MRI using a semi-automatic elastic registration. The pre- and post-LITT MRIs were registered and features were extracted. A scoring metric based on the change in median pre- and post-LITT feature values was introduced, which allowed us to identify the most treatment responsive features. Our results show that (1) image characteristics for treatment effects and residual disease are different, and (2) the change of feature values between pre- and post-LITT MRIs can be a quantitative biomarker for treatment response. Finally, using feature change improved discrimination between the residual disease and treatment effects.

Objectives: To assess the image quality of T2-weighted (T2w) magnetic resonance imaging of the prostate and the visibility of prostate cancer at 7 Tesla (T)., Materials & Methods: Seventeen prostate cancer patients underwent T2w imaging at 7T with only an external transmit/receive array coil. Three radiologists independently scored images for image quality, visibility of anatomical structures, and presence of artefacts. Krippendorff's alpha and weighted kappa statistics were used to assess inter-observer agreement. Visibility of prostate cancer lesions was assessed by directly linking the T2w images to the confirmed location of prostate cancer on histopathology., Results: T2w imaging at 7T was achievable with 'satisfactory' (3/5) to 'good' (4/5) quality. Visibility of anatomical structures was predominantly scored as 'satisfactory' (3/5) and 'good' (4/5). If artefacts were present, they were mostly motion artefacts and, to a lesser extent, aliasing artefacts and noise. Krippendorff's analysis revealed an α = 0.44 between three readers for the overall image quality scores. Clinically significant cancer lesions in both peripheral zone and transition zone were visible at 7T., Conclusion: T2w imaging with satisfactory to good quality can be routinely acquired, and cancer lesions were visible in patients with prostate cancer at 7T using only an external transmit/receive body array coil., Key Points: • Satisfactory to good T2-weighted image quality of the prostate is achievable at 7T. • Periprostatic lipids appear hypo-intense compared to healthy peripheral zone tissue at 7T. • Prostate cancer is visible on T2-weighted MRI at 7T.

Objective: In this article, we describe the fundamentals of multiparametric MRI in bladder cancer and provide an overview of the currently available data concerning this new imaging technology. Urinary bladder cancer is a relatively common malignancy, especially in elderly patients. Treatment outcome and prognosis are strongly related to adequate local and regional tumor staging. Unfortunately, clinical understaging frequently occurs, which negatively influences prognosis. Therefore, advanced imaging techniques are needed to adequately stage bladder cancer patients. MRI is currently the best imaging technique for local and nodal staging in bladder cancer patients because of its superior soft-tissue contrast without exposure to ionizing radiation. Important improvements in MRI technology have led to the introduction of multiparametric MRI, combining anatomic and functional sequences., Conclusion: The first results of multiparametric MRI seem promising, especially in detection, staging, and follow-up of bladder cancer. However, more studies are needed with larger study populations to define the exact place of multiparametric MRI in bladder cancer patients.

The use of an ultrasound probe or a needle guide during biopsy deforms both the rectal wall and the prostate, resulting in lesion motion. An accurate patient-specific finite element (FE)-based biomechanical model can be used to predict prostate deformations. In this study, an FE model of a prostate phantom is developed using magnetic resonance images, while soft-tissue elasticity is estimated in vivo using an ultrasound-based acoustic radiation force impulse imaging technique. This study confirms that three-dimensional FE-predicted prostate deformation is predominantly dependent on accurate modelling of prostate geometry and boundary conditions. Upon application of various compressive displacements, our results show that a linear elastic FE model can accurately predict prostate deformations. The maximum global error between FE-predicted simulations and experimental results is 0.76 mm. Moreover, the effect of including the urethra, puboprostatic ligament and urinary bladder on prostate deformations is investigated by a sensitivity study.

Objectives: The objective of this study was to evaluate the role of 3-T multiparametric magnetic resonance imaging (MP-MRI) and magnetic resonance-guided biopsy (MRGB) in early risk restratification of patients on active surveillance at 3 and 12 months of follow-up., Materials and Methods: Within 4 hospitals participating in a large active surveillance trial, a side study was initiated. Pelvic magnetic resonance imaging, prostate MP-MRI, and MRGB were performed at 3 and 12 months (latter prostate MP-MRI and MRGB only) after prostate cancer diagnosis in 1 of the 4 participating hospitals. Cancer-suspicious regions (CSRs) were defined on prostate MP-MRI using Prostate Imaging Reporting And Data System (PI-RADS) scores.Risk restratification criteria for active surveillance discontinuance were (1) histopathologically proven magnetic resonance imaging suspicion of node/bone metastases and/or (2) a Gleason growth pattern (GGP) 4 and/or 5 and/or cancer multifocality (≥3 foci) in MRGB specimens of a CSR on MP-MRI., Results: From 2009 to 2012, a total of 64 of 82 patients were consecutively and prospectively included and underwent MP-MRI and a subsequent MRGB. At 3 and 12 months of follow-up, 14% (9/64) and 10% (3/30) of the patients were risk-restratified on the basis of MP-MRI and MRGB. An overall CSR PI-RADS score of 1 or 2 had a negative predictive value of 84% (38/45) for detection of any prostate cancer and 100% (45/45) for detection of a GGP 4 or 5 containing cancer upon MRGB, respectively. A CSR PI-RADS score of 4 or higher had a sensitivity of 92% (11/12) for detection of a GGP 4 or 5 containing cancer upon MRGB., Conclusions: Application of MP-MRI and MRGB in active surveillance may contribute in early identification of patients with GGP 4 or 5 containing cancers at 3 months of follow-up. If, during further follow-up, a PI-RADS score of 1 or 2 continues to have a negative predictive value for GGP 4 or 5 containing cancers, a PI-RADS standardized reported MP-MRI may be a promising tool for the selection of prostate cancer patients suitable for active surveillance.

Objective: 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)., Materials and Methods: 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., Results: 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., Conclusion: The high specificity with variable but high NPVs and sensitivities implies a potential role for multiparametric MRI in detecting prostate cancer.

Objective: To establish a consensus on the utility of multiparametric magnetic resonance imaging (mpMRI) to identify patients for focal therapy., Methods: Urological surgeons, radiologists, and basic researchers, from Europe and North America participated in a consensus meeting about the use of mpMRI in focal therapy of prostate cancer. The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible. All participants are listed among the authors. Topics specifically did not include staging of prostate cancer, but rather identifying the optimal requirements for performing MRI, and the current status of optimally performed mpMRI to (i) determine focality of prostate cancer (e.g. localising small target lesions of ≥0.5 mL), (ii) to monitor and assess the outcome of focal ablation therapies, and (iii) to identify the diagnostic advantages of new MRI methods. In addition, the need for transperineal template saturation biopsies in selecting patients for focal therapy was discussed, if a high quality mpMRI is available. In other words, can mpMRI replace the role of transperineal saturation biopsies in patient selection for focal therapy?, Results: Consensus was reached on most key aspects of the meeting; however, on definition of the optimal requirements for mpMRI, there was one dissenting voice. mpMRI is the optimum approach to achieve the objectives needed for focal therapy, if made on a high quality machine (3T with/without endorectal coil or 1.5T with endorectal coil) and judged by an experienced radiologist. Structured and standardised reporting of prostate MRI is paramount. State of the art mpMRI is capable of localising small tumours for focal therapy. State of the art mpMRI is the technique of choice for follow-up of focal ablation., Conclusions: The present evidence for MRI in focal therapy is limited. mpMRI is not accurate enough to consistently grade tumour aggressiveness. Template-guided saturation biopsies are no longer necessary when a high quality state of the art mpMRI is available; however, suspicious lesions should always be confirmed by (targeted) biopsy., (© 2013 The Authors. BJU International © 2013 BJU International.)