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Background: Most oesophagogastric adenocarcinomas (OGAs) and colorectal cancers (CRCs) are mismatch repair proficient (MMRp), responding poorly to immune checkpoint inhibition. We evaluated the safety and efficacy of domatinostat (histone deacetylase inhibitor) plus avelumab (anti-PD-L1 antibody) in patients with previously treated inoperable, advanced/metastatic MMRp OGA and CRC., Patients and Methods: Eligible patients were evaluated in a multicentre, open-label dose escalation/dose expansion phase II trial. In the escalation phase, patients received escalating doses of domatinostat [100 mg once daily (OD), 200 mg OD, 200 mg twice daily (BD)] orally for 14 days followed by continuous dosing plus avelumab 10 mg/kg administered intravenously 2-weekly (2qw) to determine the recommended phase II dose (RP2D). The trial expansion phase evaluated the best objective response rate (ORR) during 6 months by RECIST version 1.1 using a Simon two-stage optimal design with 2/9 and 1/10 responses required to proceed to stage 2 in the OGA and CRC cohorts, respectively., Results: Patients (n = 40) were registered between February 2019 and October 2021. Patients in the dose escalation phase (n = 12) were evaluated to confirm the RP2D of domatinostat 200 mg BD plus avelumab 10 mg/kg. No dose-limiting toxicities were observed. Twenty-one patients were treated at the RP2D, 19 (9 OGA and 10 CRC) were assessable for the best ORR; 2 patients with CRC did not receive combination treatment and were not assessable for the primary endpoint analysis. Six patients were evaluated in the dose escalation and expansion phases. In the OGA cohort, the best ORR was 22.2% (95% one-sided confidence interval lower bound 4.1) and the median duration of disease control was 11.3 months (range 9.9-12.7 months). No responses were observed in the CRC cohort. No treatment-related grade 3-4 adverse events were reported at the RP2D., Conclusions: Responses in the OGA cohort met the criteria to expand to stage 2 of recruitment with an acceptable safety profile. There was insufficient signal in the CRC cohort to progress to stage 2., Trial Registration: NCT03812796 (registered 23 rd January 2019)., Competing Interests: Disclosure DC received research funding from Clovis, Eli-Lilly, 4SC, Bayer, Celgene, Leap and Roche and sits on the scientific advisory board for OVIBIO. IC is on the advisory board of Eli-Lilly, Bristol Myers Squibb (BMS), MSD, Roche, Merck, AstraZeneca, OncXerna, Boehringer Ingelheim, Incyte, Astella, GSK, SOTIO, Eisai, Daiichi-Sankyo, Taiho, Servier, Seagen, Turning Point Therapeutics, Novartis, BioNTech, Takeda and Elevation Oncology; received research funding from Eli-Lilly and Janssen-Cilag; and honoraria from Eli-Lilly, Eisai, Servier and Roche. NS has served on advisory boards for Pfizer, Servier, AstraZeneca, MSD Oncology, Novartis, Guardant, GSK, Gilead, Seagen and Janssen; received research funding from Merck, AstraZeneca, BMS, Pfizer and Guardant Health; and honoraria from Merck, Novartis, MSD Oncology, Eli-Lilly, Pierre Fabre, Amgen, Eli-Lilly Bangladesh, GSK, Seagen, BMS, AstraZeneca and Servier. SR receives financial support from Boehringer, Merck, Servier and Bayer; has served on advisory boards for HOOKIPA, Bayer, BeiGene, AstraZeneca, Merck, Seagen and Servier. CF has received financial support from AAA and Servier. ES receives financial support from the NIHR Biomedical Research Centre in Oxford; receives grants and personal fees from Bristol Myers Squibb and AstraZeneca; receives personal fees from Amgen, Daiichi Sankyo, Mirati, Merck, Viracta, Astellas, Novartis, Pfizer, Zymeworks and BeiGene, outside the submitted work; receives nonfinancial support from Mirati; and is the European Organisation for Research and Treatment of Cancer Gastric Cancer Taskforce Chair and an Ireland Oesophagogastric Cancer Group Trustee. WM has consulting and advisory roles with Ipsen, Novartis, Pfizer, MSD, BMS and Servier; has been involved in the speakers’ bureau with Ipsen, Novartis, MSD and Servier; has travel grants from MSD, Ipsen, BMS and Servier; and institutional grants from Nordic and MSD. The other authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Whole-body magnetic resonance imaging (WB-MRI) has been demonstrated to be efficient and cost-effective for cancer staging. The study aim was to develop a machine learning (ML) algorithm to improve radiologists' sensitivity and specificity for metastasis detection and reduce reading times., Materials and Methods: A retrospective analysis of 438 prospectively collected WB-MRI scans from multicenter Streamline studies (February 2013-September 2016) was undertaken. Disease sites were manually labeled using Streamline reference standard. Whole-body MRI scans were randomly allocated to training and testing sets. A model for malignant lesion detection was developed based on convolutional neural networks and a 2-stage training strategy. The final algorithm generated lesion probability heat maps. Using a concurrent reader paradigm, 25 radiologists (18 experienced, 7 inexperienced in WB-/MRI) were randomly allocated WB-MRI scans with or without ML support to detect malignant lesions over 2 or 3 reading rounds. Reads were undertaken in the setting of a diagnostic radiology reading room between November 2019 and March 2020. Reading times were recorded by a scribe. Prespecified analysis included sensitivity, specificity, interobserver agreement, and reading time of radiology readers to detect metastases with or without ML support. Reader performance for detection of the primary tumor was also evaluated., Results: Four hundred thirty-three evaluable WB-MRI scans were allocated to algorithm training (245) or radiology testing (50 patients with metastases, from primary 117 colon [n = 117] or lung [n = 71] cancer). Among a total 562 reads by experienced radiologists over 2 reading rounds, per-patient specificity was 86.2% (ML) and 87.7% (non-ML) (-1.5% difference; 95% confidence interval [CI], -6.4%, 3.5%; P = 0.39). Sensitivity was 66.0% (ML) and 70.0% (non-ML) (-4.0% difference; 95% CI, -13.5%, 5.5%; P = 0.344). Among 161 reads by inexperienced readers, per-patient specificity in both groups was 76.3% (0% difference; 95% CI, -15.0%, 15.0%; P = 0.613), with sensitivity of 73.3% (ML) and 60.0% (non-ML) (13.3% difference; 95% CI, -7.9%, 34.5%; P = 0.313). Per-site specificity was high (>90%) for all metastatic sites and experience levels. There was high sensitivity for the detection of primary tumors (lung cancer detection rate of 98.6% with and without ML [0.0% difference; 95% CI, -2.0%, 2.0%; P = 1.00], colon cancer detection rate of 89.0% with and 90.6% without ML [-1.7% difference; 95% CI, -5.6%, 2.2%; P = 0.65]). When combining all reads from rounds 1 and 2, reading times fell by 6.2% (95% CI, -22.8%, 10.0%) when using ML. Round 2 read-times fell by 32% (95% CI, 20.8%, 42.8%) compared with round 1. Within round 2, there was a significant decrease in read-time when using ML support, estimated as 286 seconds (or 11%) quicker ( P = 0.0281), using regression analysis to account for reader experience, read round, and tumor type. Interobserver variance suggests moderate agreement, Cohen κ = 0.64; 95% CI, 0.47, 0.81 (with ML), and Cohen κ = 0.66; 95% CI, 0.47, 0.81 (without ML)., Conclusions: There was no evidence of a significant difference in per-patient sensitivity and specificity for detecting metastases or the primary tumor using concurrent ML compared with standard WB-MRI. Radiology read-times with or without ML support fell for round 2 reads compared with round 1, suggesting that readers familiarized themselves with the study reading method. During the second reading round, there was a significant reduction in reading time when using ML support., Competing Interests: Conflicts of interest and sources of funding: A.G.R. is part of the advisory board of RoClub. This study was funded by the National Institute of Health Research Efficacy and Mechanism Evaluation Programme (trial registration: ISRCTN 23068310). The project is supported by the Imperial College London National Institute for Health Research Biomedical Research Centre, CRUK Imperial Centre, National Institute for Health Research University College London Hospitals Biomedical Research Centre, NIHR Biomedical Research Centre, and the NIHR Clinical Research Facilities and the Royal Marsden Hospital and Institute of Cancer Research. S.T. is an NIHR senior investigator. This research has been conducted using the UK Biobank Resource., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This study aimed to assess the image quality of apparent diffusion coefficient (ADC) maps derived from conventional diffusion-weighted MRI and fractional intracellular volume maps (FIC) from VERDICT MRI (Vascular, Extracellular, Restricted Diffusion for Cytometry in Tumours) in patients from the INNOVATE trial. The inter-reader agreement was also assessed., Methods: Two readers analysed both ADC and FIC maps from 57 patients enrolled in the INNOVATE prospective trial. Image quality was assessed using the Prostate Imaging Quality (PI-QUAL) score and a subjective image quality Likert score (Likert-IQ). The image quality of FIC and ADC were compared using a Wilcoxon Signed Ranks test. The inter-reader agreement was assessed with Cohen's kappa., Results: There was no statistically significant difference between the PI-QUAL score for FIC datasets compared to ADC datasets for either reader (p = 0.240 and p = 0.614). Using the Likert-IQ score, FIC image quality was higher compared to ADC (p = 0.021) as assessed by reader-1 but not for reader-2 (p = 0.663). The inter-reader agreement was 'fair' for PI-QUAL scoring of datasets with FIC maps at 0.27 (95% confidence interval; 0.08-0.46) and ADC datasets at 0.39 (95% confidence interval 0.22-0.57). For Likert scoring, the inter-reader agreement was also 'fair' for FIC maps at 0.38 (95% confidence interval; 0.10-0.65) and substantial for ADC maps at 0.62 (95% confidence interval; 0.39-0.86)., Conclusion: Image quality was comparable for FIC and ADC. The inter-reader agreement was similar when using PIQUAL for both FIC and ADC datasets but higher for ADC maps compared to FIC maps using the image quality Likert score., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Purpose: Radiofrequency ablation (RFA) is a curative treatment option for small lung metastases, which conventionally involves multiple freehand manipulations until the treating electrode is satisfactorily positioned. Stereotactic and robotic guidance has been gaining popularity for liver ablation, although has not been established in lung ablation. The purpose of this study is to determine the feasibility, safety, and accuracy of robotic RFA for pulmonary metastases, and compare procedures with a conventional freehand cohort., Methods: A single center study with prospective robotic cohort, and retrospective freehand cohort. RFA was performed under general anesthesia using high frequency jet ventilation and CT guidance. Main outcomes were (i) feasibility/technical success (ii) safety using Common Terminology Criteria for Adverse Events (iii) targeting accuracy (iv) number of needle manipulations for satisfactory ablation. Robotic and freehand cohorts were compared using Mann-Whitney U tests for continuous variables, and Fisher's exact for categorical variables., Results: Thirty-nine patients (mean age 65 ± 13 years, 20 men) underwent ablation of 44 pulmonary metastases at single specialist cancer center between July 2019 and August 2022. 20 consecutive participants underwent robotic ablation, and 20 consecutive patients underwent freehand ablation. All 20/20 (100%) robotic procedures were technically successful, and none were converted to freehand procedures. There were 6/20 (30%) adverse events in the robotic cohort, and 15/20 (75%) in the freehand cohort (P = 0.01). Robotic placement was highly accurate with 6 mm tip-to-target distance (range 0-14 mm) despite out-of-plane approaches, with fewer manipulations than freehand placement (median 0 vs. 4.5 manipulations, P < 0.001 and 7/22, 32% vs. 22/22, 100%, P < 0.001)., Conclusions: Robotic radiofrequency ablation of pulmonary metastases with general anesthesia and high frequency jet ventilation is feasible and safe. Targeting accuracy is high, and fewer needle/electrode manipulations are required to achieve a satisfactory position for ablation than freehand placement, with early indications of reduced complications., (© 2023. The Author(s).)

Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is poorly understood. Here, we analyse matched cancer and normal tissue samples from 200 patients and verify that ST6GAL1 is upregulated in prostate cancer tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), we identify larger branched α2,6 sialylated N-glycans that show specificity to prostate tumour tissue. We also monitored ST6GAL1 in plasma samples from >400 patients and reveal ST6GAL1 levels are significantly increased in the blood of men with prostate cancer. Using both in vitro and in vivo studies, we demonstrate that ST6GAL1 promotes prostate tumour growth and invasion. Our findings show ST6GAL1 introduces α2,6 sialylated N-glycans on prostate cancer cells and raise the possibility that prostate cancer cells can secrete active ST6GAL1 enzyme capable of remodelling glycans on the surface of other cells. Furthermore, we find α2,6 sialylated N-glycans expressed by prostate cancer cells can be targeted using the sialyltransferase inhibitor P-3F AX -Neu5Ac. Our study identifies an important role for ST6GAL1 and α2,6 sialylated N-glycans in prostate cancer progression and highlights the opportunity to inhibit abnormal sialylation for the development of new prostate cancer therapeutics. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Aim: To characterise training for, and conduct of, image-guided liver tumour ablation amongst UK interventional radiologists., Materials and Methods: A web-based survey of British Society of Interventional Radiology members was carried out between 31 August to 1 October 2022. Twenty-eight questions were designed, covering four domains: (1) respondent background, (2) training, (3) current practice, and (4) operator technique., Results: One hundred and six responses were received, with an 87% completion rate and an approximate response rate of 13% of society members. All UK regions were represented, with the majority from London (22/105, 21%). Seventy-two out of 98 (73%) were either extremely or very interested in learning about liver ablation during training, although levels of exposure varied widely, and 37/103 (36%) had no exposure. Performed numbers of cases also varied widely, between 1-10 cases and >100 cases per operator annually. All (53/53) used microwave energy, and most routinely used general anaesthesia (47/53, 89%). Most 33/53 (62%) did not have stereotactic navigation system, and 25/51(49%) always, 18/51 (35%) never, and 8/51(16%) sometimes gave contrast medium (mean 40, SD 32%) after procedures. Fusion software to judge ablation completeness was never used by 86% (43/55), sometimes used by 9% (5/55), and always used by 13% (7/55) of respondents., Conclusion: Although there are high levels of interest in image-guided liver ablation amongst UK interventional radiologists, training arrangements, operator experience, and procedural technique vary widely. As image-guided liver ablation evolves, there is a growing need to standardise training and techniques, and develop the evidence base to ensure high-quality oncological outcomes., (Copyright © 2023. Published by Elsevier Ltd.)

Prostate cancer is the most common cancer in men and it is estimated that over 350,000 men worldwide die of prostate cancer every year. There remains an unmet clinical need to improve how clinically significant prostate cancer is diagnosed and develop new treatments for advanced disease. Aberrant glycosylation is a hallmark of cancer implicated in tumour growth, metastasis, and immune evasion. One of the key drivers of aberrant glycosylation is the dysregulated expression of glycosylation enzymes within the cancer cell. Here, we demonstrate using multiple independent clinical cohorts that the glycosyltransferase enzyme GALNT7 is upregulated in prostate cancer tissue. We show GALNT7 can identify men with prostate cancer, using urine and blood samples, with improved diagnostic accuracy than serum PSA alone. We also show that GALNT7 levels remain high in progression to castrate-resistant disease, and using in vitro and in vivo models, reveal that GALNT7 promotes prostate tumour growth. Mechanistically, GALNT7 can modify O-glycosylation in prostate cancer cells and correlates with cell cycle and immune signalling pathways. Our study provides a new biomarker to aid the diagnosis of clinically significant disease and cements GALNT7-mediated O-glycosylation as an important driver of prostate cancer progression., (© 2023. The Author(s).)

Background In men suspected of having prostate cancer (PCa), up to 50% of men with positive multiparametric MRI (mpMRI) findings (Prostate Imaging Reporting and Data System [PI-RADS] or Likert score of 3 or higher) have no clinically significant (Gleason score ≤3+3, benign) biopsy findings. Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumor (VERDICT) MRI analysis could improve the stratification of positive mpMRI findings. Purpose To evaluate VERDICT MRI, mpMRI-derived apparent diffusion coefficient (ADC), and prostate-specific antigen density (PSAD) as determinants of clinically significant PCa (csPCa). Materials and Methods Between April 2016 and December 2019, men suspected of having PCa were prospectively recruited from two centers and underwent VERDICT MRI and mpMRI at one center before undergoing targeted biopsy. Biopsied lesion ADC, lesion-derived fractional intracellular volume (FIC), and PSAD were compared between men with csPCa and those without csPCa, using nonparametric tests subdivided by Likert scores. Area under the receiver operating characteristic curve (AUC) was calculated to test diagnostic performance. Results Among 303 biopsy-naive men, 165 study participants (mean age, 65 years ± 7 [SD]) underwent targeted biopsy; of these, 73 had csPCa. Median lesion FIC was higher in men with csPCa (FIC, 0.53) than in those without csPCa (FIC, 0.18) for Likert 3 ( P = .002) and Likert 4 (0.60 vs 0.28, P < .001) lesions. Median lesion ADC was lower for Likert 4 lesions with csPCa (0.86 × 10 -3 mm 2 /sec) compared with lesions without csPCa (1.12 × 10 -3 mm 2 /sec, P = .03), but there was no evidence of a difference for Likert 3 lesions (0.97 × 10 -3 mm 2 /sec vs 1.20 × 10 -3 mm 2 /sec, P = .09). PSAD also showed no difference for Likert 3 (0.17 ng/mL 2 vs 0.12 ng/mL 2 , P = .07) or Likert 4 (0.14 ng/mL 2 vs 0.12 ng/mL 2 , P = .47) lesions. The diagnostic performance of FIC (AUC, 0.96; 95% CI: 0.93, 1.00) was higher ( P = .02) than that of ADC (AUC, 0.85; 95% CI: 0.79, 0.91) and PSAD (AUC, 0.74; 95% CI: 0.66, 0.82) for the presence of csPCa in biopsied lesions. Conclusion Lesion fractional intracellular volume enabled better classification of clinically significant prostate cancer than did apparent diffusion coefficient and prostate-specific antigen density. Clinical trial registration no. NCT02689271 © RSNA, 2022 Online supplemental material is available for this article.

Background: Magnetic resonance imaging (MRI) can be used to target tumour components in biopsy procedures, while the ability to precisely correlate histology and MRI signal is crucial for imaging biomarker validation. Robotic MRI/computed tomography (CT) fusion biopsy offers the potential for this without in-gantry biopsy, although requires development., Methods: Test-retest T1 and T2 relaxation times, attenuation (Hounsfield units, HU), and biopsy core quality were prospectively assessed (January-December 2021) in a range of gelatin, agar, and mixed gelatin/agar solutions of differing concentrations on days 1 and 8 after manufacture. Suitable materials were chosen, and four biopsy phantoms were constructed with twelve spherical 1-3-cm diameter targets visible on MRI, but not on CT. A technical pipeline was developed, and intraoperator and interoperator reliability was tested in four operators performing a total of 96 biopsies. Statistical analysis included T1, T2, and HU repeatability using Bland-Altman analysis, Dice similarity coefficient (DSC), and intraoperator and interoperator reliability., Results: T1, T2, and HU repeatability had 95% limits-of-agreement of 8.3%, 3.4%, and 17.9%, respectively. The phantom was highly reproducible, with DSC of 0.93 versus 0.92 for scanning the same or two different phantoms, respectively. Hit rate was 100% (96/96 targets), and all operators performed robotic biopsies using a single volumetric acquisition. The fastest procedure time was 32 min for all 12 targets., Conclusions: A reproducible biopsy phantom was developed, validated, and used to test robotic MRI/CT-fusion biopsy. The technique was highly accurate, reliable, and achievable in clinically acceptable timescales meaning it is suitable for clinical application., (© 2022. The Author(s) under exclusive licence to European Society of Radiology.)

Aim: To report the first UK experience of cryoablation in desmoid fibromatosis (DF) with particular focus on technique, safety, and efficacy., Materials and Methods: Patients were selected at multidisciplinary tumour board meetings at a specialist cancer hospital. Radiation dose, procedure duration, and number of cryoprobes were compared for small versus large tumours (>10 cm long axis). Response at magnetic resonance imaging (MRI) was evaluated using different criteria, and percentage agreement with clinical response as assessed in oncology clinic calculated., Results: Thirteen procedures were performed in 10 patients (eight women, median age 51 years, IQR 42-69 years) between February 2019 and August 2021. Procedures for large tumours had higher radiation dose (2,012 ± 1,012 versus 1,076 ± 519 mGy·cm, p=0.048) used more cryoprobes (13 ± 7 versus 4 ± 2, p=0.009), and were more likely to have residual unablated tumour (38 ± 37% versus 7.5 ± 10%, p=0.045). Adverse events were minor apart from one transient radial nerve palsy. Eight of 10 patients had symptomatic benefit at clinical follow-up (median 353 days, IQR 86-796 days), and three started systemic therapy mean 393 days later. All patients who had complete ablation demonstrated symptomatic response, with no instances of repeat treatment, recurrence, or need for systemic therapy during the study period. All progression occurred outside ablation zones., Conclusion: Cryoablation for symptomatic DF is a reproducible technique with low, transient toxicity, where one or two treatments can achieve a meaningful response. Where possible, the ablation ice ball should fully cover DF tumours., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

A shift in radiology to a data-driven specialty has been unlocked by synergistic developments in imaging biomarkers (IB) and computational science. This is advancing the capability to deliver "virtual biopsies" within oncology. The ability to non-invasively probe tumour biology both spatially and temporally would fulfil the potential of imaging to inform management of complex tumours; improving diagnostic accuracy, providing new insights into inter- and intra-tumoral heterogeneity and individualised treatment planning and monitoring. Soft tissue sarcomas (STS) are rare tumours of mesenchymal origin with over 150 histological subtypes and notorious heterogeneity. The combination of inter- and intra-tumoural heterogeneity and the rarity of the disease remain major barriers to effective treatments. We provide an overview of the process of successful IB development, the key imaging and computational advancements in STS including quantitative magnetic resonance imaging, radiomics and artificial intelligence, and the studies to date that have explored the potential biological surrogates to imaging metrics. We discuss the promising future directions of IBs in STS and illustrate how the routine clinical implementation of a virtual biopsy has the potential to revolutionise the management of this group of complex cancers and improve clinical outcomes., Competing Interests: RJ is the recipient of grants/research support from Merck Sharp & Dohme and GlaxoSmithKline. RJ is the recipient of consultation fees from Adaptimmune, Athenex, Blueprint Medicines, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immune Design, Lilly, Merck, PharmaMar and UpToDate. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Arthur, Johnston, Winfield, Blackledge, Jones, Huang and Messiou.)

Objective: A commercially available CT-guided robot offers enhanced abilities in planning, targeting, and confirming accurate needle placement. In this short communication, we describe our first UK experience of robotic interventional oncology procedures., Methods: We describe the device, discuss installation, operation, and report upon needle insertion success, accuracy (path deviation; PD and tip deviation; TD), number of adjustments, complications, and procedural success., Results: Nine patients (seven males), median age 66 years (range 43-79) were consented for biopsy or ablation between March and April 2021. Needle placement in biopsy was more accurate than ablation (median 1 vs 11 mm PD and 1 vs 20 mm TD) and required fewer adjustments (median 0 vs 5). No complications arose, and all procedures were successful (diagnostic material obtained or complete ablation at follow-up)., Conclusion: Short procedure times and very high levels of accuracy were readily achieved with biopsy procedures, although tumour ablation was less accurate which likely reflects higher procedural complexity., Advances in Knowledge: Achieving highly accurate robotic biopsy with is feasible within a very short time span. Further work is required to maximise the potential of robotic guidance in tumour ablation procedures, which is likely due to higher complexity giving a longer learning curve.

Multiparametric magnetic resonance imaging (mpMRI) of the prostate is used by radiologists to identify, score, and stage abnormalities that may correspond to clinically significant prostate cancer (CSPCa). Automatic assessment of prostate mpMRI using artificial intelligence algorithms may facilitate a reduction in missed cancers and unnecessary biopsies, an increase in inter-observer agreement between radiologists, and an improvement in reporting quality. In this work, we introduce AutoProstate, a deep learning-powered framework for automatic MRI-based prostate cancer assessment. AutoProstate comprises of three modules: Zone-Segmenter, CSPCa-Segmenter, and Report-Generator. Zone-Segmenter segments the prostatic zones on T2-weighted imaging, CSPCa-Segmenter detects and segments CSPCa lesions using biparametric MRI, and Report-Generator generates an automatic web-based report containing four sections: Patient Details , Prostate Size and PSA Density , Clinically Significant Lesion Candidates , and Findings Summary . In our experiment, AutoProstate was trained using the publicly available PROSTATEx dataset, and externally validated using the PICTURE dataset. Moreover, the performance of AutoProstate was compared to the performance of an experienced radiologist who prospectively read PICTURE dataset cases. In comparison to the radiologist, AutoProstate showed statistically significant improvements in prostate volume and prostate-specific antigen density estimation. Furthermore, AutoProstate matched the CSPCa lesion detection sensitivity of the radiologist, which is paramount, but produced more false positive detections.

Objectives : To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaining for novel biomarkers. Methods: The INNOVATE study was set up to evaluate the validity of novel fluidic biomarkers in men with suspected prostate cancer who undergo pre-biopsy mpMRI. We report the characteristics of this clinical cohort, the distribution of clinical serum biomarkers, PSA and PSA density (PSAD), and compare the mpMRI Likert scoring system to the Prostate Imaging-Reporting and Data System v2.1 (PI-RADS) in men undergoing biopsy. Results : 340 men underwent mpMRI to evaluate suspected prostate cancer. 193/340 (57%) men had subsequent MRI-targeted prostate biopsy. Clinically significant prostate cancer (csigPCa), i.e., overall Gleason ≥ 3 + 4 of any length OR maximum cancer core length (MCCL) ≥4 mm of any grade including any 3 + 3, was found in 96/195 (49%) of biopsied patients. Median PSA (and PSAD) was 4.7 (0.20), 8.0 (0.17), and 9.7 (0.31) ng/mL (ng/mL/mL) in mpMRI scored Likert 3,4,5 respectively for men with csigPCa on biopsy. The space for novel biomarkers was shown to be within the group of men with mpMRI scored Likert3 (178/340) and 4 (70/350), in whom an additional of 40% (70/178) men with mpMRI-scored Likert3, and 37% (26/70) Likert4 could have been spared biopsy. PSAD is already considered clinically in this cohort to risk stratify patients for biopsy, despite this 67% (55/82) of men with mpMRI-scored Likert3, and 55% (36/65) Likert4, who underwent prostate biopsy had a PSAD below a clinical threshold of 0.15 (or 0.12 for men aged <50 years). Different thresholds of PSA and PSAD were assessed in mpMRI-scored Likert4 to predict csigPCa on biopsy, to achieve false negative levels of ≤5% the proportion of patients whom who test as above the threshold were unsuitably high at 86 and 92% of patients for PSAD and PSA respectively. When PSA was re tested in a sub cohort of men repeated PSAD showed its poor reproducibility with 43% (41/95) of patients being reclassified. After PI-RADS rescoring of the biopsied lesions, 66% (54/82) of the Likert3 lesions received a different PI-RADS score. Conclusions : The addition of simple biochemical and radiological markers (Likert and PSAD) facilitate the streamlining of the mpMRI-diagnostic pathway for suspected prostate cancer but there remains scope for improvement, in the introduction of novel biomarkers for risk assessment in Likert3 and 4 patients, future application of novel biomarkers tested in a Likert cohort would also require re-optimization around Likert3/PI-RADS2, as well as reproducibility testing.

Background: To evaluate the efficacy, safety and overall clinical outcome of multiprobe SRFA as a treatment for recurrent colorectal liver metastases after hepatic resection (HR)., Methods: A retrospective, single center study carried out between 2006 and 2018. 64 consecutive patients with recurrent or new CRLM after previous HR were treated by SRFA for 217 lesions (median size 2.7 cm, 1-7.5) in 103 ablation sessions. Endpoints consisted of i) technical efficacy ii) complication and mortality rates iii) local and distant recurrence, iv) disease free survival (DFS), and v) overall survival (OS)., Results: 213/217 tumors were successfully ablated at initial SRFA (97.7% primary technical efficacy rate). Four tumors required repeat ablation, resulting in a secondary technical efficacy rate of 99.5% (216/217). Local recurrence developed in 25/217 lesions (11.5%). Major complication rate was 5.8% (6/103 sessions) and mortality rate was 1.0% (1/103 ablation sessions), respectively.1-, 3-, and 5- year OS rates from date of first SRFA were 90.1%, 46.2%, and 34.8% (median 33.1 months). DFS rates were 54.2%, 17.2%, and 17.2%, at 1-, 3- and 5- years, respectively (median 13.3 months)., Conclusion: SRFA is a safe, feasible and effective option for CRLM after HR with low morbidity levels and favorable clinical outcome., Competing Interests: Declaration of competing interest All authors have no conflicts to declare., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

To assess the safety and clinical outcomes of multi-probe stereotactic radiofrequency ablation (SRFA) for very large (≥8 cm) primary and metastatic liver tumors with curative treatment intent. A retrospective, single center study carried out between 01.2005 and 06.2018. 34 consecutive patients had a total of 41 primary and metastatic liver tumors with a median size of 9.0 cm (8.0-18.0 cm) at initial SRFA. Patients were treated under CT guidance using a 3D navigation system. Endpoints consisted of (i) technical efficacy; primary - requiring one treatment, and secondary - requiring two treatments (ii) complication and mortality rates (iii) local and distant recurrence (LR), (iv) disease free survival (DFS), (v) overall survival (OS). 33/41 tumors were successfully ablated at initial SRFA (80.5% primary technical efficacy rate (PTE)). Four tumors required repeat ablation, resulting in a secondary technical efficacy (STE) rate of 90.2%. Local tumor recurrence (LR) developed in 4 of 41 tumors (9.8%). The 30-day perioperative mortality was 2.3% (1/ 44 ablations). The total major complication rate was 20.5% (9 of 44 ablations). Three of nine (33.3%) major complications, such as pleural effusion, pneumothoraces or perihepatic hemorrhages were relatively easy to treat. The overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 87.1%, 71.8%, and 62.8% for patients with hepatocellular carcinoma (HCC) and 87.5%, 70.0% and 70.0% for patients with intrahepatic cholangiocarcinoma (ICC) respectively. Patients with metastatic disease had OS rates of 77.8% and 22.2% at 1- and 3- years. The clinical results of SRFA in this study are encouraging and warrant a prospective multicenter study. SRFA may become one of the best therapeutic choices for a growing number of patients with primary and metastatic liver cancer.

Objective: The purpose of this study was: To test whether machine learning classifiers for transition zone (TZ) and peripheral zone (PZ) can correctly classify prostate tumors into those with/without a Gleason 4 component, and to compare the performance of the best performing classifiers against the opinion of three board-certified radiologists., Methods: A retrospective analysis of prospectively acquired data was performed at a single center between 2012 and 2015. Inclusion criteria were (i) 3-T mp-MRI compliant with international guidelines, (ii) Likert ≥ 3/5 lesion, (iii) transperineal template ± targeted index lesion biopsy confirming cancer ≥ Gleason 3 + 3. Index lesions from 164 men were analyzed (119 PZ, 45 TZ). Quantitative MRI and clinical features were used and zone-specific machine learning classifiers were constructed. Models were validated using a fivefold cross-validation and a temporally separated patient cohort. Classifier performance was compared against the opinion of three board-certified radiologists., Results: The best PZ classifier trained with prostate-specific antigen density, apparent diffusion coefficient (ADC), and maximum enhancement (ME) on DCE-MRI obtained a ROC area under the curve (AUC) of 0.83 following fivefold cross-validation. Diagnostic sensitivity at 50% threshold of specificity was higher for the best PZ model (0.93) when compared with the mean sensitivity of the three radiologists (0.72). The best TZ model used ADC and ME to obtain an AUC of 0.75 following fivefold cross-validation. This achieved higher diagnostic sensitivity at 50% threshold of specificity (0.88) than the mean sensitivity of the three radiologists (0.82)., Conclusions: Machine learning classifiers predict Gleason pattern 4 in prostate tumors better than radiologists., Key Points: • Predictive models developed from quantitative multiparametric magnetic resonance imaging regarding the characterization of prostate cancer grade should be zone-specific. • Classifiers trained differently for peripheral and transition zone can predict a Gleason 4 component with a higher performance than the subjective opinion of experienced radiologists. • Classifiers would be particularly useful in the context of active surveillance, whereby decisions regarding whether to biopsy are necessitated.

Background: Luminal water imaging (LWI) suffers less from imaging artifacts than the diffusion-weighted imaging used in multiparametric MRI of the prostate. LWI obtains multicompartment tissue information from a multiecho T 2 dataset., Purpose: To compare a simplified LWI technique with apparent diffusion coefficient (ADC) in classifying lesions based on groupings of PI-RADS v2 scores. Secondary aims were to investigate whether LWI differentiates between histologically confirmed tumor and normal tissue as effectively as ADC, and whether LWI is correlated with the multicompartment parameters of the vascular, extracellular, and restricted diffusion for cytometry in tumors (VERDICT) diffusion model., Study Type: A subset of a larger prospective study., Population: In all, 65 male patients aged 49-79 were scanned., Field Strength/sequence: A 32-echo T 2 and a six b-value diffusion sequence (0, 90, 500, 1500, 2000, 3000 s/mm 2 ) at 3T., Assessment: Regions of interest were placed by a board-certified radiologist in areas of lesion and benign tissue and given PI-RADS v2 scores., Statistical Tests: Receiver operating characteristic and logistic regression analyses were performed., Results: LWI classifies tissue as PI-RADS 1,2 or PI-RADS 3,4,5 with an area under curve (AUC) value of 0.779, compared with 0.764 for ADC. LWI differentiated histologically confirmed malignant from nonmalignant tissue with AUC, sensitivity, and specificity values of 0.81, 75%, and 87%, compared with 0.75, 83%, and 67% for ADC. The microstructural basis of the LWI technique is further suggested by the correspondence with the VERDICT diffusion-based microstructural imaging technique, with α, A 1 , A 2 , and LWF showing significant correlations., Data Conclusion: LWI alone can predict PI-RADS v2 score groupings and detect histologically confirmed tumors with an ability similar to ADC alone without the limitations of diffusion-weighted MRI. This is important, given that ADC has an advantage in these tests as it already informs PI-RADS v2 scoring. LWI also provides multicompartment information that has an explicit biophysical interpretation, unlike ADC., Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:910-917., (© 2018 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: Compare the performance of zone-specific multi-parametric-MRI (mp-MRI) diagnostic models in prostate cancer detection with experienced radiologists., Methods: A single-centre, IRB approved, prospective STARD compliant 3 T MRI test dataset of 203 patients was generated to test validity and generalisability of previously reported 1.5 T mp-MRI diagnostic models. All patients included within the test dataset underwent 3 T mp-MRI, comprising T2, diffusion-weighted and dynamic contrast-enhanced imaging followed by transperineal template ± targeted index lesion biopsy. Separate diagnostic models (transition zone (TZ) and peripheral zone (PZ)) were applied to respective zones. Sensitivity/specificity and the area under the receiver operating characteristic curve (ROC-AUC) were calculated for the two zone-specific models. Two radiologists (A and B) independently Likert scored test 3 T mp-MRI dataset, allowing ROC analysis for each radiologist for each prostate zone., Results: Diagnostic models applied to the test dataset demonstrated a ROC-AUC = 0.74 (95% CI 0.67-0.81) in the PZ and 0.68 (95% CI 0.61-0.75) in the TZ. Radiologist A/B had a ROC-AUC = 0.78/0.74 in the PZ and 0.69/0.69 in the TZ. Radiologists A and B each scored 51 patients in the PZ and 41 and 45 patients respectively in the TZ as Likert 3. The PZ model demonstrated a ROC-AUC = 0.65/0.67 for the patients Likert scored as indeterminate by radiologist A/B respectively, whereas the TZ model demonstrated a ROC-AUC = 0.74/0.69., Conclusion: Zone-specific mp-MRI diagnostic models demonstrate generalisability between 1.5 and 3 T mp-MRI protocols and show similar classification performance to experienced radiologists for prostate cancer detection. Results also indicate the ability of diagnostic models to classify cases with an indeterminate radiologist score., Key Points: • MRI diagnostic models had similar performance to experienced radiologists for classification of prostate cancer. • MRI diagnostic models may help radiologists classify tumour in patients with indeterminate Likert 3 scores.

Advances in information and communication technologies enable the public to contribute to emergency response. For instance, reporting systems set up during recent disasters allowed affected people to submit testimonies about conditions on the ground. In addition, the public has analysed data and helped to mobilise and deliver relief resources. To plan intentionally for an integrative emergency response system in the networked age, this research explores two subject areas: (i) the organisational and technical determinants of relationships forged between formal organisations and participatory online groups established by the public; and (ii) the consequences of the outcomes generated by these relationships. Four in-depth case studies were selected for the analysis, which revealed that resource dependence, shared understanding, and the use of certain types of information technology influence the formation of such relationships. Furthermore, healthy collaborative relationships increase the chances of desirable results, including inter-organisational alignment and minimal long-term harm owing to a disaster., (© 2019 The Author(s). Disasters © Overseas Development Institute, 2019.)

Background: Whole-body MRI (WB-MRI) could be an alternative to multimodality staging of colorectal cancer, but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in colorectal cancer., Methods: The Streamline C trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed colorectal cancer. Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or polyp cancer. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs), and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN43958015, and is complete., Findings: Between March 26, 2013, and Aug 19, 2016, 1020 patients were screened for eligibility. 370 patients were recruited, 299 of whom completed the trial; 68 (23%) had metastasis at baseline. Pathway sensitivity was 67% (95% CI 56 to 78) for WB-MRI and 63% (51 to 74) for standard pathways, a difference in sensitivity of 4% (-5 to 13, p=0·51). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (95% [95% CI 92-97]) and standard pathways (93% [90-96], p=0·48). Agreement with the multidisciplinary team's final treatment decision was 96% for WB-MRI and 95% for the standard pathway. Time to complete staging was shorter for WB-MRI (median, 8 days [IQR 6-9]) than for the standard pathway (13 days [11-15]); a 5-day (3-7) difference. WB-MRI required fewer tests (median, one [95% CI 1 to 1]) than did standard pathways (two [2 to 2]), a difference of one (1 to 1). Mean per-patient staging costs were £216 (95% CI 211-221) for WB-MRI and £285 (260-310) for standard pathways., Interpretation: WB-MRI staging pathways have similar accuracy to standard pathways and reduce the number of tests needed, staging time, and cost., Funding: UK National Institute for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To determine the diagnostic accuracy and interobserver concordance of whole-body (WB)-MRI, vs. 99m Tc bone scintigraphy (BS) and 18 fluoro-ethyl-choline ( 18 F-choline) PET/CT for the primary staging of intermediate/high-risk prostate cancer., Methods: An institutional review board approved prospective cohort study carried out between July 2012 and November 2015, whereby 56 men prospectively underwent 3.0-T multiparametric (mp)-WB-MRI in addition to BS (all patients) ± 18 F-choline PET/CT (33 patients). MRI comprised pre- and post-contrast modified Dixon (mDixon), T2-weighted (T2W) imaging, and diffusion-weighted imaging (DWI). Patients underwent follow-up mp-WB-MRI at 1 year to derive the reference standard. WB-MRIs were reviewed by two radiologists applying a 6-point scale and a locked sequential read (LSR) paradigm for the suspicion of nodal (N) and metastatic disease (M1a and M1b)., Results: The mean sensitivity/specificity of WB-MRI for N1 disease was 1.00/0.96 respectively, compared with 1.00/0.82 for 18 F-choline PET/CT. The mean sensitivity and specificity of WB-MRI, 18 F-choline PET/CT, and BS were 0.90/0.88, 0.80/0.92, and 0.60/1.00 for M1b disease. ROC-AUC did not show statistically significant improvement for each component of the LSR; mean ROC-AUC 0.92, 0.94, and 0.93 (p < 0.05) for mDixon + DWI, + T2WI, and + contrast respectively. WB-MRI had an interobserver concordance (κ) of 0.79, 0.68, and 0.58 for N1, M1a, and M1b diseases respectively., Conclusions: WB-MRI provides high levels of diagnostic accuracy for both nodal and metastatic bone disease, with higher levels of sensitivity than BS for metastatic disease, and similar performance to 18 F-choline PET/CT. T2 and post-contrast mDixon had no significant additive value above a protocol comprising mDixon and DWI alone., Key Points: • A whole-body MRI protocol comprising unenhanced mDixon and diffusion-weighted imaging provides high levels of diagnostic accuracy for the primary staging of intermediate- and high-risk prostate cancer. • The diagnostic accuracy of whole-body MRI is much higher than that of bone scintigraphy, as currently recommended for clinical use. • Staging using WB-MRI, rather than bone scintigraphy, could result in better patient stratification and treatment delivery than is currently provided to patients worldwide.

Background: Whole-body magnetic resonance imaging (WB-MRI) could be an alternative to multi-modality staging of non-small-cell lung cancer (NSCLC), but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in NSCLC., Methods: The Streamline L trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed NSCLC that was potentially radically treatable on diagnostic chest CT (defined as stage IIIb or less). Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or histologies other than NSCLC. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs) and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN50436483, and is complete., Findings: Between Feb 26, 2013, and Sept 5, 2016, 976 patients were screened for eligibility. 353 patients were recruited, 187 of whom completed the trial; 52 (28%) had metastasis at baseline. Pathway sensitivity was 50% (95% CI 37-63) for WB-MRI and 54% (41-67) for standard pathways, a difference of 4% (-7 to 15, p=0·73). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (93% [88-96]) and standard pathways (95% [91-98], p=0·45). Agreement with the multidisciplinary team's final treatment decision was 98% for WB-MRI and 99% for the standard pathway. Time to complete staging was shorter for WB-MRI (13 days [12-14]) than for the standard pathway (19 days [17-21]); a 6-day (4-8) difference. The number of tests required was similar WB-MRI (one [1-1]) and standard pathways (one [1-2]). Mean per-patient costs were £317 (273-361) for WBI-MRI and £620 (574-666) for standard pathways., Interpretation: WB-MRI staging pathways have similar accuracy to standard pathways, and reduce the staging time and costs., Funding: UK National Institute for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Over 1 million men are diagnosed with prostate cancer each year worldwide, with a wide range of research programs requiring access to patient tissue samples for development of improved diagnoses and treatments. A random sampling of prostate tissue is sufficient for certain research studies; however, there is growing research need to target areas of the aggressive tumor as fresh tissue. Here we set out to develop a new pathway "PEOPLE: PatiEnt prOstate samPLes for rEsearch" to collect high-quality fresh tissue for research use, using magnetic resonance imaging (MRI) to target areas of tumor and benign tissue., Methods: Prostate tissue was sampled following robotic radical prostatectomy, using MRI data to target areas of benign and tumor tissue. Initially, 25 cases were sampled using MRI information from clinical notes. A further 59 cases were sampled using an optimized method that included specific MRI measurements of tumor location along with additional exclusion criteria. All cases were reviewed in batches with detailed clinical and histopathological data recorded. For one subset of samples, DNA was extracted and underwent quality control. Ex vivo culture was carried out using the gelatin sponge method for an additional subset., Results: Tumor was successfully fully or partially targeted in 64% of the initial cohort and 70% of the optimized cohort. DNA of high quality and concentration was isolated from 39 tumor samples, and ex vivo culture was successfully carried out in three cases with tissue morphology, proliferation, and apoptosis remaining comparable before and after 72 hours culture., Conclusion: Here we report initial data from the PEOPLE pathway; using a method for targeting areas of tumor within prostate samples using MRI. This method operates alongside the standard clinical pathway and minimizes additional input from surgical, radiological, and pathological teams, while preserving surgical margins and diagnostic tissue., (© 2019 Wiley Periodicals, Inc.)

Background: Renal patients with a tunnelled haemodialysis line are at risk of fibrin 'sheath' formation which can lead to occlusion. Dysfunctional lines are best treated by catheter exchange with a new subcutaneous tunnel; however, there is a risk of scarring, venous stenosis, potential loss of valuable access as well as the risk of infection., Method: We report a retrospective review of our experience using tunnelled line intraluminal plasty (TuLIP) in 11 patients over 16 months with fibrin sheath formation on pre-existing tunnelled haemodialysis catheters., Result: All patients responded well to treatment with median line patency post TuLIP reaching 112 days., Conclusion: TuLIP may have a role in extending catheter lifespan and delaying more invasive intervention.

The VERDICT framework for modelling diffusion MRI data aims to relate parameters from a biophysical model to histological features used for tumour grading in prostate cancer. Validation of the VERDICT model is necessary for clinical use. This study compared VERDICT parameters obtained ex vivo with histology in five specimens from radical prostatectomy. A patient-specific 3D-printed mould was used to investigate the effects of fixation on VERDICT parameters and to aid registration to histology. A rich diffusion data set was acquired in each ex vivo prostate before and after fixation. At both time points, data were best described by a two-compartment model: the model assumes that an anisotropic tensor compartment represents the extracellular space and a restricted sphere compartment models the intracellular space. The effect of fixation on model parameters associated with tissue microstructure was small. The patient-specific mould minimized tissue deformations and co-localized slices, so that rigid registration of MRI to histology images allowed region-based comparison with histology. The VERDICT estimate of the intracellular volume fraction corresponded to histological indicators of cellular fraction, including high values in tumour regions. The average sphere radius from VERDICT, representing the average cell size, was relatively uniform across samples. The primary diffusion direction from the extracellular compartment of the VERDICT model aligned with collagen fibre patterns in the stroma obtained by structure tensor analysis. This confirmed the biophysical relationship between ex vivo VERDICT parameters and tissue microstructure from histology., (© 2019 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Background Biologic specificity of diffusion MRI in relation to prostate cancer aggressiveness may improve by examining separate components of the diffusion MRI signal. The Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumors (VERDICT) model estimates three distinct signal components and associates them to (a) intracellular water, (b) water in the extracellular extravascular space, and (c) water in the microvasculature. Purpose To evaluate the repeatability, image quality, and diagnostic utility of intracellular volume fraction (FIC) maps obtained with VERDICT prostate MRI and to compare those maps with apparent diffusion coefficient (ADC) maps for Gleason grade differentiation. Materials and Methods Seventy men (median age, 62.2 years; range, 49.5-82.0 years) suspected of having prostate cancer or undergoing active surveillance were recruited to a prospective study between April 2016 and October 2017. All men underwent multiparametric prostate and VERDICT MRI. Forty-two of the 70 men (median age, 67.7 years; range, 50.0-82.0 years) underwent two VERDICT MRI acquisitions to assess repeatability of FIC measurements obtained with VERDICT MRI. Repeatability was measured with use of intraclass correlation coefficients (ICCs). The image quality of FIC and ADC maps was independently evaluated by two board-certified radiologists. Forty-two men (median age, 64.8 years; range, 49.5-79.6 years) underwent targeted biopsy, which enabled comparison of FIC and ADC metrics in the differentiation between Gleason grades. Results VERDICT MRI FIC demonstrated ICCs of 0.87-0.95. There was no significant difference between image quality of ADC and FIC maps (score, 3.1 vs 3.3, respectively; P = .90). FIC was higher in lesions with a Gleason grade of at least 3+4 compared with benign and/or Gleason grade 3+3 lesions (mean, 0.49 ± 0.17 vs 0.31 ± 0.12, respectively; P = .002). The difference in ADC between these groups did not reach statistical significance (mean, 1.42 vs 1.16 × 10 -3 mm 2 /sec; P = .26). Conclusion Fractional intracellular volume demonstrates high repeatability and image quality and enables better differentiation of a Gleason 4 component cancer from benign and/or Gleason 3+3 histology than apparent diffusion coefficient. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Sigmund and Rosenkrantz in this issue.

Multi-Atlas based Segmentation (MAS) algorithms have been successfully applied to many medical image segmentation tasks, but their success relies on a large number of atlases and good image registration performance. Choosing well-registered atlases for label fusion is vital for an accurate segmentation. This choice becomes even more crucial when the segmentation involves organs characterized by a high anatomical and pathological variability. In this paper, we propose a new genetic atlas selection strategy (GAS) that automatically chooses the best subset of atlases to be used for segmenting the target image, on the basis of both image similarity and segmentation overlap. More precisely, the key idea of GAS is that if two images are similar, the performances of an atlas for segmenting each image are similar. Since the ground truth of each atlas is known, GAS first selects a predefined number of similar images to the target, then, for each one of them, finds a near-optimal subset of atlases by means of a genetic algorithm. All these near-optimal subsets are then combined and used to segment the target image. GAS was tested on single-label and multi-label segmentation problems. In the first case, we considered the segmentation of both the whole prostate and of the left ventricle of the heart from magnetic resonance images. Regarding multi-label problems, the zonal segmentation of the prostate into peripheral and transition zone was considered. The results showed that the performance of MAS algorithms statistically improved when GAS is used., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study is to evaluate the safety and efficacy of stereotactic radiofrequency ablation (SRFA) for the treatment of subcardiac hepatocellular carcinoma (HCC). Material and methods: From 2003 to 2018, 79 consecutive patients underwent 104 multi-probe SRFA sessions for the treatment of 114 subcardiac HCC with a median size of 2.5 cm (0.5-9.5 cm). The results were compared with a randomly selected control group of 79 patients with 242 HCC with a median size of 2.0 cm (0.5-12 cm) following SRFA in other (non-subcardiac) locations with propensity score matching. Results: The 95.6% of the tumors were successfully treated by the first ablation session (primary technical efficacy rate) and 99.1% after the second session (secondary technical efficacy rate). Local tumor recurrence developed in 8 nodules (7.0%). Major complication and perioperative mortality rates were 7.7% (8/104) and 1% (1/104), respectively. The overall survival (OS) rates from the date of the first SRFA with single subcardiac HCCs were 92%, 77% and 65% at 1, 3 and 5 years, respectively, with a median OS of 90.6 months. The disease-free survival (DFS) after SRFA was 75, 34 and 34%, at 1, 3 and 5 years, respectively, with a median DFS of 19.1 months. There was no statistically significant difference with the control group in terms of local tumor control, safety, OS and DFS. Conclusion: SRFA of subcardiac tumors is as safe and efficacious as when treating tumors remote from the heart.

Microwave ablation (MWA) has been proposed to suffer less from the heat sink effect compared to radiofrequency ablation but has been reported to cause extension of the ablation zone along intrahepatic vessels in clinical practice. To study this effect in detail, eight fresh porcine livers were perfused in an ex vivo organ perfusion system. Livers were perfused with oxygenated, O-positive human blood at 37 °C. Perfusion was discontinued immediately before ablation in the non-perfused group (n = 4) whilst in the perfused group (n = 4) perfusion was maintained during MWA (140 W X 2 min). Large intrahepatic vessels (> 6 mm) were avoided using ultrasound. MWA zones were bisected within 30 min of perfusion termination and sections were fixed in formalin and stained with H&E and NADH to assess cell viability. Magnetic resonance imaging (MRI) was performed on two livers (one perfused, one non-perfused) to provide imaging correlation before sectioning. Twenty-one out of a total of 30 MW ablation zones (70%) showed extension of the ablation zone along a vessel. There was no statistically significant difference (p = 1) in the incidence of ablation zone extension between perfused (9/13, 69%) and non-perfused organs (12/17, 71%). MRI also demonstrated ablation zone extension along blood vessels correlating with macroscopy in two livers. NADH staining also confirmed extension of the ablation zone. Liver MWA appears to be commonly associated with propagated thermal injury along adjacent vessels and occurs independent of active blood flow. In order to avoid possible complications through non-target tissue injury, this effect requires further investigation.

Objectives: To identify areas of agreement and disagreement in the implementation of multi-parametric magnetic resonance imaging (mpMRI) of the prostate in the diagnostic pathway., Materials and Methods: Fifteen UK experts in prostate mpMRI and/or prostate cancer management across the UK (involving nine NHS centres to provide for geographical spread) participated in a consensus meeting following the Research and Development Corporation and University of California-Los Angeles (UCLA-RAND) Appropriateness Method, and were moderated by an independent chair. The experts considered 354 items pertaining to who can request an mpMRI, prostate mpMRI protocol, reporting guidelines, training, quality assurance (QA) and patient management based on mpMRI levels of suspicion for cancer. Each item was rated for agreement on a 9-point scale. A panel median score of ≥7 constituted 'agreement' for an item; for an item to reach 'consensus', a panel majority scoring was required., Results: Consensus was reached on 59% of items (208/354); these were used to provide recommendations for the implementation of prostate mpMRI in the UK. Key findings include prostate mpMRI requests should be made in consultation with the urological team; mpMRI scanners should undergo QA checks to guarantee consistently high diagnostic quality scans; scans should only be reported by trained and experienced radiologists to ensure that men with unsuspicious prostate mpMRI might consider avoiding an immediate biopsy., Conclusions: Our consensus statements demonstrate a set of criteria that are required for the practical dissemination of consistently high-quality prostate mpMRI as a diagnostic test before biopsy in men at risk., (© 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: To determine whether indeterminate (Likert-score 3/5) peripheral zone (PZ) multiparametric MRI (mpMRI) studies are classifiable by prostate-specific antigen (PSA), PSA density (PSAD), Prostate Imaging Reporting And Data System version 2 (PI-RADS&#95;v2) rescoring and morphological MRI features., Methods: Men with maximum Likert-score 3/5 within their PZ were retrospectively selected from 330 patients who prospectively underwent prostate mpMRI (3 T) without an endorectal coil, followed by 20-zone transperineal template prostate mapping biopsies ＋/- focal lesion-targeted biopsy. PSAD was calculated using pre-biopsy PSA and MRI-derived volume. Two readers A and B independently assessed included men with both Likert-assessment and PI-RADS&#95;v2. Both readers then classified mpMRI morphological features in consensus. Men were divided into two groups: significant cancer (≥ Gleason 3 ＋ 4) or insignificant cancer (≤ Gleason 3 ＋ 3)/no cancer. Comparisons between groups were made separately for PSA & PSAD using Mann-Whitney test and morphological descriptors with Fisher's exact test. PI-RADS&#95;v2 and Likert-assessment were descriptively compared and percentage inter-reader agreement calculated., Results: 76 males were eligible for PSA & PSAD analyses, 71 for PI-RADS scoring, and 67 for morphological assessment (excluding significant image artefacts). Unlike PSA (p = 0.915), PSAD was statistically different (p = 0.004) between the significant [median: 0.19 ng ml - 2 (interquartile range: 0.13-0.29)] and non-significant/no cancer [median: 0.13 ng ml - 2 (interquartile range: 0.10-0.17)] groups. Presence of mpMRI morphological features was not significantly different between groups. Subjective Likert-assessment discriminated patients with significant cancer better than PI-RADS&#95;v2. Inter-reader percentage agreement was 83% for subjective Likert-assessment and 56% for PI-RADS&#95;v2., Conclusion: PSAD may categorize presence of significant cancer in patients with Likert-scored 3/5 PZ mpMRI findings. Advances in knowledge: PSAD may be used in indeterminate PZ mpMRI to guide decisions between biopsy vs monitoring.

Public engagement in collaborative natural resource management necessitates shared understanding and collaboration. Empathic perspective-taking is a critical facilitator of shared understanding and positive social interactions, such as collaboration. Yet there is currently little understanding about how to reliably generate empathic perspective-taking and collaboration, particularly in situations involving the unequal distribution of environmental resources or power. Here we examine how experiencing the loss or gain of social power influenced empathic perspective-taking and behavior within a computer-mediated scenario. Participants (n = 180) were randomly assigned to each condition: high resources, low resources, lose resources, gain resources. Contrary to our expectations, participants in the perspective-taking condition, specifically those who lost resources, also lost perspective taking and exhibited egoistic behavior. This finding suggests that resource control within the collaborative process is a key contextual variable that influences perspective-taking and collaborative behavior. Moreover, the observed relationship between perspective-taking and egoistic behavior within a collaborative resource sharing exercise suggests that when resource control or access is unequal, interventions to promote perspective-taking deserve careful consideration., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate multiparametric-MRI (mpMRI) derived histogram textural-analysis parameters for detection of transition zone (TZ) prostatic tumour., Methods: Sixty-seven consecutive men with suspected prostate cancer underwent 1.5T mpMRI prior to template-mapping-biopsy (TPM). Twenty-six men had 'significant' TZ tumour. Two radiologists in consensus matched TPM to the single axial slice best depicting tumour, or largest TZ diameter for those with benign histology, to define single-slice whole TZ-regions-of-interest (ROIs). Textural-parameter differences between single-slice whole TZ-ROI containing significant tumour versus benign/insignificant tumour were analysed using Mann Whitney U test. Diagnostic accuracy was assessed by receiver operating characteristic area under curve (ROC-AUC) analysis cross-validated with leave-one-out (LOO) analysis., Results: ADC kurtosis was significantly lower (p < 0.001) in TZ containing significant tumour with ROC-AUC 0.80 (LOO-AUC 0.78); the difference became non-significant following exclusion of significant tumour from single-slice whole TZ-ROI (p = 0.23). T1-entropy was significantly lower (p = 0.004) in TZ containing significant tumour with ROC-AUC 0.70 (LOO-AUC 0.66) and was unaffected by excluding significant tumour from TZ-ROI (p = 0.004). Combining these parameters yielded ROC-AUC 0.86 (LOO-AUC 0.83)., Conclusion: Textural features of the whole prostate TZ can discriminate significant prostatic cancer through reduced kurtosis of the ADC-histogram where significant tumour is included in TZ-ROI and reduced T1 entropy independent of tumour inclusion., Key Points: • MR textural features of prostate transition zone may discriminate significant prostatic cancer. • Transition zone (TZ) containing significant tumour demonstrates a less peaked ADC histogram. • TZ containing significant tumour reveals higher post-contrast T1-weighted homogeneity. • The utility of MR texture analysis in prostate cancer merits further investigation.

Purpose: To compare the size of ablation zones derived from nonperfused ex vivo livers with ablation zones created using an ex vivo perfused porcine liver model., Materials and Methods: Six fresh porcine livers were used to evaluate microwave ablation (MWA). Perfused (n = 3) and nonperfused (n = 3) livers were warmed to 37°C by oxygenated, O-positive human blood reconstituted with Ringer solution, using an organ perfusion circuit. During MWA, perfusion was discontinued in the nonperfused group and maintained in the perfused group. After MWA (140 watts × 2 min at 2.45 GHz) with the Acculis MTA System (AngioDynamics, Latham, New York), ablation zones were bisected sagittally. Sections were stained with nicotinamide adenine dinucleotide (NADH) and hematoxylin-eosin to assess viability of cells in ablation and marginal zones., Results: Comparison of 22 MWA zones (9 in perfused group, 13 in nonperfused group) was performed. Ablation zones demonstrated a central "white" and peripheral "red" zone. Cells in the white zone were nonviable with no NADH staining. The red zone showed progressive NADH staining toward the periphery, suggesting incomplete cell death. White and red zones of the perfused group were significantly smaller compared with the nonperfused group (short axis, 17.8 mm ± 2.7 vs 21.1 mm ± 3.2, P = .003; long axis, 40.69 mm ± 3.9 vs 39.63 mm ± 5.2, P = .44; intermediate zone,1.33 mm ± 0.04 vs 2.7 mm ± 0.14, P < .0001; mean ± SD)., Conclusions: MWA algorithms provided by this manufacturer are based on nonperfused organ data, which overestimate ablation zone size. Data from perfused liver models may be required for more accurate dosimetry guidelines., (Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.)

This article describes apparatus to aid histological validation of magnetic resonance imaging studies of the human prostate. The apparatus includes a 3D-printed patient-specific mold that facilitates aligned in vivo and ex vivo imaging, in situ tissue fixation, and tissue sectioning with minimal organ deformation. The mold and a dedicated container include MRI-visible landmarks to enable consistent tissue positioning and minimize image registration complexity. The inclusion of high spatial resolution ex vivo imaging aids in registration of in vivo MRI and histopathology data.

A 69-year-old man who presented with abdominal discomfort was, on examination, found to have a palpable abdominal mass. Contrast-enhanced CT showed a mass arising from the inferior vena cava, which biopsy confirmed to be a leiomyosarcoma. One month after chemoradiotherapy, CT demonstrated a new 15 mm solitary central right liver metastasis. Microwave ablation (MWA) of the metastasis was performed using an Acculis Sulis V system (Angiodynamics, USA) at a power of 140 Watts for 4 min, with no immediate complications. After 1 month, MRI with gadolinium was performed to assess the liver ablation zone. The MRI demonstrated thrombosis of a right inferior hepatic vein branch leading to the ablation zone and extension of the ablation zone 1 cm into the tissue around the thrombosed vessel., (2016 BMJ Publishing Group Ltd.)

Purpose of Review: To review the use of multi-parametric MRI (mpMRI) in loco-regional assessment of men with early prostate cancer., Recent Findings: mpMRI comprises anatomic T2 and T1 sequences supplemented by functional imaging techniques such as diffusion-weighted and dynamic contrast enhanced (DCE) imaging. mpMRI is gaining increasing acceptance for prostate cancer detection and staging of early disease. It can facilitate targeted therapies, guide surgical options and enable active surveillance within suitable patients. The technique can be performed at 1.5 or 3 Tesla, but sequence optimization is critical to successful implementation of mpMRI. T2 and diffusion-weighted sequences are minimal requirements and are often complemented by DCE images. When performed at high spatial resolution, DCE facilitates detection of disease, as well as assessment of extra-capsular extension, distal urethral sphincter and seminal vesicles involvement. Pre-biopsy mpMRI is recommended for both detection and staging as it avoids biopsy artefact, and when normal, has a negative predictive value of 95% for significant cancer., Summary: mpMRI reliably detects clinically significant prostate tumour and ideally should be performed prior to biopsy. It provides an accurate method for local disease staging and facilitates a growing range of treatment options for patients with early disease.

Inferior vena cava (IVC) filters are used to protect against pulmonary embolism in high-risk patients. Whilst the insertion of retrievable IVC filters is gaining popularity, a proportion of such devices cannot be removed using standard techniques. We describe a novel approach for IVC filter removal that involves snaring the filter superiorly along with the use of flexible forceps or laser devices to dissect the filter struts from the caval wall. This technique has used to successfully treat three patients without complications in whom standard techniques failed.

The aim of this study is to develop an automated method to objectively compare motion artifacts in two four-dimensional computed tomography (4D CT) image sets, and identify the one that would appear to human observers with fewer or smaller artifacts. Our proposed method is based on the difference of the normalized correlation coefficients between edge slices at couch transitions, which we hypothesize may be a suitable metric to identify motion artifacts. We evaluated our method using ten pairs of 4D CT image sets that showed subtle differences in artifacts between images in a pair, which were identifiable by human observers. One set of 4D CT images was sorted using breathing traces in which our clinically implemented 4D CT sorting software miscalculated the respiratory phase, which expectedly led to artifacts in the images. The other set of images consisted of the same images; however, these were sorted using the same breathing traces but with corrected phases. Next we calculated the normalized correlation coefficients between edge slices at all couch transitions for all respiratory phases in both image sets to evaluate for motion artifacts. For nine image set pairs, our method identified the 4D CT sets sorted using the breathing traces with the corrected respiratory phase to result in images with fewer or smaller artifacts, whereas for one image pair, no difference was noted. Two observers independently assessed the accuracy of our method. Both observers identified 9 image sets that were sorted using the breathing traces with corrected respiratory phase as having fewer or smaller artifacts. In summary, using the 4D CT data of ten pairs of 4D CT image sets, we have demonstrated proof of principle that our method is able to replicate the results of two human observers in identifying the image set with fewer or smaller artifacts.

Purpose: To determine the immediate effect on corneal thickness of cataract extraction using phacoemulsification., Design: Prospective consecutive nonrandomized humans undergoing standard small-incision phacoemulsification and intraocular lens insertion., Methods: Corneal thickness was measured immediately preoperative and postoperatively in 58 consecutive patients undergoing phacoemulsification in the absence of other ocular abnormalities. Corneal thickness was determined centrally and in the midperiphery of four quadrants. The last 17 eyes were also evaluated for the effect of pressure from a Honan balloon on corneal thickness., Setting: Faculty practice in medical school and university hospital. The cornea thinned in all five of the measured locations, with statistical significance being reached only in the four midperipheral quadrants. Pressure from the Honan balloon resulted in a negligible increase in corneal thickness preoperatively., Conclusions: Corneas were found to have thinned statistically significantly immediately after phacoemulsification; however, the degree of thinning has doubtful clinical significance and does not represent a significant dehydration of the cornea during the surgical procedure.

Objective: To compare photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) in treating spherical hyperopia using the VISX STAR S2 excimer laser., Intervention: Fifteen consecutive eyes of 15 patients underwent PRK, and 16 consecutive eyes of 16 patients underwent LASIK (follow-up: 12 months)., Main Outcome Measures: Postoperative pain, uncorrected visual acuity (UCVA), deviation from intended correction, and loss of best spectacle-corrected visual acuity (BSCVA)., Results: Mean preoperative spherical equivalent was + 2.18 diopter [D] for PRK and + 2.03D for LASIK. All PRK patients experienced significant postoperative pain that required systemic medication, whereas LASIK patients had minor and transient discomfort. Mean deviation from intended correction was -0.83D, + 0.01D, and + 0.18D at 1, 6, and 12 months after PRK, and + 0.22D, +0.30D, and + 0.40D at 1, 6, and 12 months after LASIK (P = 0.002 at 1 month). A higher proportion of LASIK eyes had a UCVA of 20/20 or better at all time points (P = 0.013 and 0.025 at 1 and 3 months, respectively). There was no statistically significant difference between both groups in BSCVA loss., Conclusions: LASIK and PRK are comparable in efficacy and safety. However, PRK was more painful, with an initial and temporary myopic over-correction that did not occur after LASIK. Stability was achieved between 3 and 6 months following PRK, and one month following LASIK.

Purpose: To compare the efficacy and safety of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) in the treatment of spherical hyperopia with use of the VISX STAR S2 excimer laser., Methods: A review of 15 consecutive patients (22 eyes) receiving PRK and 22 consecutive patients (26 eyes) receiving LASIK (median follow-up, 12 months)., Results: Mean age was 52 +/- 7 years for patients receiving PRK and 55 +/- 9 years for patients receiving LASIK. Mean preoperative spherical equivalent was +2.25 +/- 1.16 D for PRK patients and +1.81 +/- 0.92 D for LASIK patients. Mean deviation from intended correction was -0.82 +/- 0.89 D after PRK and +0.19 +/- 0.47 D after LASIK at 1 month (P < .01); +0.16 D +/- 0.37 D after PRK and +0.29 +/- 0.51 D after LASIK at 6 months (P = .906); +0.20 +/- 0.35 D after PRK and +0.37 +/- 0.44 D after LASIK at 1 year (P = .301). At 1 year, 83.3% of PRK eyes and 61.5% of hyperopic LASIK eyes were within +/- 0.50 D of intended correction (P = 1.0). At 1 year, all eyes in both groups had acuity of 20/40 or better uncorrected, and 47.1% of PRK eyes and 54.5% of LASIK eyes had acuity of 20/20 or better uncorrected (P = 1.0). At last follow-up (minimum, 6 months), 2 eyes in each group had lost 2 lines of best spectacle-correct visual acuity, but none had lost more than 2 lines. All PRK patients experienced significant postoperative pain that required systemic medication. LASIK patients had only minor, transient discomfort., Conclusion: LASIK and PRK are of comparable efficacy and safety. However, PRK was associated with significant post-operative pain, an initial and temporary myopic overshoot peaking at 1 month, and stability not occurring before 6 months. LASIK was less painful and was associated with more rapid stability (at 1 month) and a trend toward better uncorrected visual acuity, although not statistically significant.