Rectal tumors extending beyond the total mesorectal excision (TME) plane (beyond-TME) require particular multidisciplinary expertise and oncologic considerations when planning treatment. Imaging is used at all stages of the pathway, such as local tumor staging/restaging, creating an imaging-based "roadmap" to plan surgery for optimal tumor clearance, identifying treatment-related complications, which may be suitable for radiology-guided intervention, and to detect recurrent or metastatic disease, which may be suitable for radiology-guided ablative therapies. Beyond-TME and exenterative surgery have gained acceptance as potentially curative procedures for advanced tumors. Understanding the role, techniques, and pitfalls of current imaging techniques is important for both radiologists involved in the treatment of these patients and general radiologists who may encounter patients undergoing surveillance or patients presenting with surgical complications or intercurrent abdominal pathology. This review aims to outline the current and emerging roles of imaging in patients with beyond-TME and recurrent rectal malignancy, focusing on practical tips for image interpretation and surgical planning in the beyond-TME setting. Keywords: Abdomen/GI, Rectum, Oncology © RSNA, 2024..

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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 23rd January 2019)..

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..

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..

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..

PURPOSE: To compare the results of a novice with those of experienced interventional radiologists (IRs) for stereotactic radiofrequency ablation (SRFA) of malignant liver tumors in terms of safety, technical success, and local tumor control. METHODS: A database, including all SRFA procedures performed in a single center between January 2011 and December 2018 was retrospectively analyzed. A total of 39 ablation sessions performed by a novice IR were compared to the results of three more experienced IRs. Comparative SRFA sessions were selected using propensity score matching considering tumor type, age, sex, tumor size, and tumor number as matching variables. Overall, 549 target tumors were treated in 273 sessions. Median tumor size was 2.2 cm (1.0-8.5 cm) for 178 hepatocellular carcinomas (HCCs) and 3.0 cm (0.5-13.0 cm) for 371 metastases. A median of 2 (1-11) tumors were treated per session. RESULTS: No significant differences were observed when comparing the results of more experienced IRs with those of a novice IR regarding the rates of major complications (6.8% [16/234] vs. 5.1% [2/39]; p = 0.477), mortality (1.3% [2/234] vs. 0% [0/39]; p = 0.690), primary technical efficacy (98.5% [525/533] vs. 98.9% [94/95]; p = 0.735), and local recurrence (5.6% [30/533] vs. 5.3% [5/95]; p = 0.886). However, the median planning/placement time was significantly shorter for the experienced IRs (92 min vs. 119 min; p = 0.002). CONCLUSIONS: SRFA is a safe, effective, and reliable treatment option for malignant liver tumors and favorable outcomes can be achieved even by inexperienced operators with minimal supervision..

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..

BACKGROUND: Radiofrequency ablation (RFA) is subject to "heat-sink" effects, particularly for treatment of tumors adjacent to major vessels. METHODS: In this retrospective study, 104 patients with 137 tumors (40 HCC, 10 ICC and 54 metastatic liver tumors) close to (≤1 cm from) the hepatic venous confluence underwent stereotactic RFA (SRFA) between June 2003 and June 2018. Median tumor size was 3.7 cm (1.4-8.5) for HCC, 6.4 cm (0.5-11) for ICC and 3.8 cm (0.5-13) for metastases. Endpoints comprised safety, local tumor control, overall and disease-free survival. RESULTS: The overall major complication rate was 16.0% (20/125 ablations), where 8 (40%) were successfully treated by the interventional radiologist in the same anesthetic session and did not prolong hospital stay. 134/137 (97.8%) tumors were successfully ablated at initial SRFA. Local recurrence (LR) developed in 19/137 tumors (13.9%). The median and overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 51.5 months, 73.5%, 67.0%, and 49.7% for HCC, 14.6 months, 60.0%, 32.0% and 32.0% for ICC and 38.1 months, 91.4%, 56.5% and 27.9% for metastatic disease, respectively. CONCLUSION: SRFA represents a viable alternative to hepatic resection for challenging tumors at the hepatic venous confluence..

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..

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 mm2/sec) compared with lesions without csPCa (1.12 × 10-3 mm2/sec, P = .03), but there was no evidence of a difference for Likert 3 lesions (0.97 × 10-3 mm2/sec vs 1.20 × 10-3 mm2/sec, P = .09). PSAD also showed no difference for Likert 3 (0.17 ng/mL2 vs 0.12 ng/mL2, P = .07) or Likert 4 (0.14 ng/mL2 vs 0.12 ng/mL2, 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..

PURPOSE: To assess the technical outcome and local tumor control of multi-probe stereotactic radiofrequency ablation (SRFA) in a large series of patients. Furthermore, to determine factors accounting for adverse outcomes. MATERIAL AND METHODS: Between 2003 and 2018, 865 patients were treated by SRFA for 2653 primary and metastatic liver tumors with a median tumor size of 2.0 cm (0.5 - 19 cm). Primary technical efficacy (PTE) and local recurrence (LR) were evaluated, and possible predictors for adverse events analyzed using uni- and multi-variable binary logistic regression. RESULTS: Overall, 2553 of 2653 tumors were successfully ablated at initial SRFA resulting in a PTE rate of 96.2%. Predictors of lower PTE rates were age > 70 years, tumor size > 5 cm, number of probes, location close to liver capsule/organs and segment II. LR occurred in 220 of 2653 tumors (8.3%) with the following predictors: age, tumor type/size, conglomerates, segments I/IVa/IVb, number of probes and location close to major vessels/bile duct. Multivariable analysis revealed tumor size > 5 cm (odds ratio [OR] 3.153), age > 70 years (OR 1.559), and location in segment II (OR 1.772) as independent prognostic factors for PTE, whereas tumor location close to major vessels (OR 1.653) and in segment IVb (OR 2.656) were identified as independent prognostic factors of LR. CONCLUSIONS: Stereotactic RFA is an attractive option in the management of primary or metastatic liver tumors with good local tumor control, even in large tumors. The presented prognostic factors for adverse local oncological outcome might help to stratify unfavorable tumors for ablation..

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..

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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..

OBJECTIVES: To assess the frequency of major complications after multi-probe stereotactic radiofrequency ablation (SRFA) in a large cohort of patients over 15 years and to elucidate risk factors for adverse events. MATERIALS AND METHODS: A retrospective study was carried out between July 2003 and December 2018. Seven hundred ninety-three consecutive patients (median 65.0 years (0.3-88), 241 women and 552 men, were treated in 1235 SRFA sessions for 2475 primary and metastatic liver tumors with a median tumor size of 3.0 cm (0.5-18 cm). The frequency of major complications was evaluated according to SIR guidelines and putative predictors of adverse events analyzed using simple and multivariable logistic regression. RESULTS: Thirty-day mortality after SRFA was 0.5% (6/1235) with an overall major complication rate of 7.4% (91/1235). The major complication rate decreased from 11.5% (36/314) (before January 2011) to 6.0% (55/921) (p = 0.001). 50.5% (46/91) of major complications were successfully treated in the same anesthetic session by angiographic coiling for hemorrhage and chest tube insertion for pneumothorax. History of bile duct surgery/intervention, number of coaxial needles, and location of tumors in segment IVa or VIII were independent prognostic factors for major complications following multivariable logistic regression analysis. Simple logistic regression revealed the number of tumors, tumor size, location close to the diaphragm, tumor conglomerate, and segment VII as other significant predictors. CONCLUSION: SRFA of liver tumors is safe and can extend the treatment spectrum of conventional RFA. Adaptations over time combined with increasing experience resulted in a significant decrease in complications. KEY POINTS: • In 1235 ablation sessions in 793 patients over 15 years, we found a mortality rate of 0.5% (6/1235) and an overall major complication rate of 7.4%, which fell from 11.5 (36/314) to 6.0% (55/921, p = 0.001) after January 2011, likely due to procedural adaptations. • History of bile duct surgery/intervention (p = 0.013, OR = 3.290), number of coaxial needles (p = 0.026, OR = 1.052), and location of tumors in segment IVa (p = 0.016, OR = 1.989) or VIII (p = 0.038, OR = 1.635) were found to be independent prognostic factors. • Simple logistic regression revealed that number of tumors, tumor size, location close to the diaphragm, tumor conglomerates, and segment VII were other significant predictors of major complications..

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..

PURPOSE: To evaluate safety, local oncological control, long-term outcome and potential prognostic factors of stereotactic RFA (SRFA) for the treatment of BCLMs. METHODS: Between July 2003 and December 2019, 42 consecutive female patients with median age 54.0 years were treated with SRFA at our institution for 110 BCLMs in 48 ablation sessions. Median tumor size was 3.0 cm (0.8-9.0). Eighteen (42.9%) patients had extrahepatic metastasis at initial SRFA. RESULTS: Technical success rate was 100%, i.e., all coaxial needles were inserted with appropriate accuracy within 10 mm off plan and 107/110 (92.3%) BCLMs were successfully ablated at initial SRFA. Four Grade 1 (8.3%, 4/48) and one Grade 2 (2.1%, 1/48) complications occurred. No perioperative deaths occurred. Local recurrence developed in 8 of 110 tumors (7.3%). Overall survival (OS) rates of all patients at 1, 3, and 5 years from the date of the first SRFA were 84.1%, 49.3%, and 20.8% with a median OS of 32.3 months. Univariable cox regression analyses revealed age > 60 years and extrahepatic disease (without bone only metastases) as significant predictors of worse OS (p = 0.013 and 0.025, respectively). Size and number of metastases, hormone receptor status and time onset did not significantly affect OS after initial SRFA. CONCLUSIONS: SRFA is a safe, minimally invasive treatment option in the management of BCLMs, especially in younger patients without advanced extrahepatic metastasis, including those with large liver tumors..

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..

The original version of this article, published on 11 June 2019, unfortunately contained a mistake. The following correction has therefore been made in the original: In section "Multiparametric MRI review," the readers mentioned in the first sentence were partly incorrect..

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AbstractThough a stronger orientation of research and innovation with a focus on societal needs, demands, and preferences has recently become the main argument under the header of responsible research and innovation, the processes by which community members are included in studies of the future, as well as forward-looking science, technology, and innovation are underexplored. This paper explores the role of participatory agenda-setting in creating governance infrastructures that reflect community participation, boundary object creation, and experimental innovation for increased understanding of future decision tradeoffs. Drawing upon the authors’ leadership and participant observation of two participatory agenda-setting projects, this paper contributes to our understanding of what participatory agenda-setting looks like in practice at a boundary organization in higher education. Though not a traditional research study with control and experiment groups, we seek to share our insights and lessons learned from our leadership of two projects with inherent participatory agenda-setting components. The paper culminates in recommendations for future projects which seek to incorporate laypeople into future-oriented research..

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..

Purpose: To evaluate whether 'invisible' liver tumors on CT can be treated by stereotactic radiofrequency ablation (SRFA) using fusion of pre-ablation MRI.Methods: In this retrospective case-control study, 60 patients (14 with Hepatocellular carcinoma (HCC) and 46 with metastatic liver tumors) with CT 'invisible' lesions underwent SRFA using MRI-fusion between June 2005 and June 2018 ('fusion group'). For comparison, 60 patients who underwent SRFA without image fusion were selected using nearest neighbor propensity score matching ('control group'). Endpoints consisted of local tumor control, safety, overall and disease-free survival.Results: Major complications occurred in 6/69 ablations (8.7%) in the fusion group and in 6/89 ablations (6.7%) in the control group (p = 0.434). Primary technical efficacy rate (i.e., successful initial ablation) was 96.6% (28/29) for HCC and 97.9% (166/170) for metastatic disease in the fusion group and 100% (33/33) and 93.3% (184/194) in the control group, respectively (p = 0.468 and 0.064). Local recurrence (LR) was observed in 1/29 (3.5%) HCCs and in 6/170 metastases (4.0%) in the fusion group and 1/33 (3.0%) and 21/196 (10.7%) in the control group, respectively. The LR rate of metastasis in the control group was significantly higher (p = 0.007), although differences in OS and DFS did not reach statistical significance.Conclusions: Image fusion using pre-procedural MRI allows for ablation of CT-'invisible' liver tumors that are otherwise untreatable. Moreover, local oncological control was higher in metastatic liver tumors versus matched controls which suggests it could be useful tool for all stereotactic radiofrequency ablation procedures..

VERDICT (vascular, extracellular and restricted diffusion for cytometry in tumours) estimates and maps microstructural features of cancerous tissue non-invasively using diffusion MRI. The main purpose of this study is to address the high computational time of microstructural model fitting for prostate diagnosis, while retaining utility in terms of tumour conspicuity and repeatability. In this work, we adapt the accelerated microstructure imaging via convex optimization (AMICO) framework to linearize the estimation of VERDICT parameters for the prostate gland. We compare the original non-linear fitting of VERDICT with the linear fitting, quantifying accuracy with synthetic data, and computational time and reliability (performance and precision) in eight patients. We also assess the repeatability (scan-rescan) of the parameters. Comparison of the original VERDICT fitting versus VERDICT-AMICO showed that the linearized fitting (1) is more accurate in simulation for a signal-to-noise ratio of 20 dB; (2) reduces the processing time by three orders of magnitude, from 6.55 seconds/voxel to 1.78 milliseconds/voxel; (3) estimates parameters more precisely; (4) produces similar parametric maps and (5) produces similar estimated parameters with a high Pearson correlation between implementations, r2  > 0.7. The VERDICT-AMICO estimates also show high levels of repeatability. Finally, we demonstrate that VERDICT-AMICO can estimate an extra diffusivity parameter without losing tumour conspicuity and retains the fitting advantages. VERDICT-AMICO provides microstructural maps for prostate cancer characterization in seconds..

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..

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..

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 mm2/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..

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..

A significant proportion of men with rising prostate-specific antigen (PSA) levels after radical prostatectomy (RP) fail prostate fossa (PF) salvage radiation treatment (SRT). This study was done to assess the ability of 18F-fluoromethylcholine (18F-FCH) PET/CT (hereafter referred to as 18F-FCH), 68Ga-HBED-CC PSMA-11 PET/CT (hereafter referred to as PSMA), and pelvic multiparametric MRI (hereafter referred to as pelvic MRI) to identify men who will best benefit from SRT. Methods: Prospective, multisite imaging studies were carried out in men who had rising PSA levels after RP, high-risk features, and negative/equivocal conventional imaging results and who were being considered for SRT. 18F-FCH (91/91), pelvic MRI (88/91), and PSMA (31/91) (Australia) were all performed within 2 wk. Imaging was interpreted by experienced local/central interpreters who were masked with regard to other imaging results, with consensus being reached for discordant interpretations. Expected management was documented before and after imaging, and data about all treatments and PSA levels were collected for 3 y. The treatment response to SRT was defined as a reduction in PSA levels of >50% without androgen deprivation therapy. Results: The median Gleason score, PSA level at imaging, and PSA doubling time were 8, 0.42 (interquartile range, 0.29-0.93) ng/mL, and 5.0 (interquartile range, 3.3-7.6) months. Recurrent prostate cancer was detected in 28% (25/88) by pelvic MRI, 32% (29/91) by 18F-FCH, and 42% (13/31) by PSMA. This recurrence was found within the PF in 21.5% (19/88), 13% (12/91), and 19% (6/31) and at sites outside the PF (extra-PF) in 8% (7/88), 19% (17/91), and 32% (10/31) by MRI, 18F-FCH, and PSMA, respectively (P < 0.004). A total of 94% (16/17) of extra-PF sites on 18F-FCH were within the pelvic MRI field. Intrapelvic extra-PF disease was detected in 90% (9/10) by PSMA and in 31% (5/16) by MRI. 18F-FCH changed management in 46% (42/91), and MRI changed management in 24% (21/88). PSMA provided additional management changes over 18F-FCH in 23% (7/31). The treatment response to SRT was higher in men with negative results or disease confined to the PF than in men with extra-PF disease (18F-FCH 73% [32/44] versus 33% [3/9] [P < 0.02], pelvic MRI 70% [32/46] versus 50% [2/4] [P was not significant], and PSMA 88% [7/8] versus 14% [1/7] [P < 0.005]). Men with negative imaging results (MRI, 18F-FCH, or PSMA) had high (78%) SRT response rates. Conclusion:18F-FCH and PSMA had high detection rates for extra-PF disease in men with negative/equivocal conventional imaging results and rising PSA levels after RP. These findings affected management and treatment responses, suggesting an important role for PET in triaging men being considered for curative SRT..

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..

OBJECTIVES: To determine the diagnostic accuracy and interobserver concordance of whole-body (WB)-MRI, vs. 99mTc bone scintigraphy (BS) and 18fluoro-ethyl-choline (18F-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) ± 18F-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 18F-choline PET/CT. The mean sensitivity and specificity of WB-MRI, 18F-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 18F-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 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..

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..

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..

Our purpose was to assess whether the addition of data from multiparametric pelvic MRI (mpMR) and whole-body MRI (wbMR) to the interpretation of 18F-fluoromethylcholine (18F-FCH) or 68Ga-HBED-CC PSMA-11 (68Ga-PSMA) PET/CT (=PET) improves the detection of local tumor recurrence or of nodal and distant metastases in patients after radical prostatectomy with biochemical failure. Methods: The current analysis was performed as part of a prospective, multicenter trial on 18F-FCH or 68Ga-PSMA PET, mpMR, and wbMR. Eligible men had an elevated level of prostate-specific antigen (PSA) (>0.2 ng/mL) and high-risk features (Gleason score > 7, PSA doubling time < 10 mo, or PSA > 1.0 ng/mL) with negative or equivocal conventional imaging results. PET was interpreted with mpMR and wbMR in consensus by 2 radiologists and compared with prospective interpretation of PET or MRI alone. Performance measures of each modality (PET, MRI, and PET/mpMR-wbMR) were compared for each radiotracer and each individual patient (for 18F-FCH, or 68Ga-PSMA for patients who had 68Ga-PSMA PET) and to a composite reference standard. Results: There were 86 patients with PET (18F-FCH [n = 76] and/or 68Ga-PSMA [n = 26]) who had mpMR and wbMR. Local tumor recurrence was detected in 20 of 76 (26.3%) on 18F-FCH PET/mpMR, versus 11 of 76 (14.5%) on 18F-FCH PET (P = 0.039), and in 11 of 26 (42.3%) on 68Ga-PSMA PET/mpMR, versus 6 of 26 (23.1%) on 68Ga-PSMA PET (P = 0.074). Per patient, PET/mpMR was more often positive for local tumor recurrence than PET (P = 0.039) or mpMR (P = 0.019). There were 20 of 86 patients (23.3%) with regional nodal metastases on both PET/wbMR and PET (P = 1.0) but only 12 of 86 (14%) on wbMR (P = 0.061). Similarly, there were more nonregional metastases detected on PET/wbMR than on PET (P = 0.683) or wbMR (P = 0.074), but these differences did not reach significance. Compared with the composite reference standard for the detection of disease beyond the prostatic fossa, PET/wbMR, PET, and wbMR had sensitivity of 50%, 50%, and 8.3%, respectively, and specificity of 97.1%, 97.1%, and 94.1%, respectively. Conclusion: Interpretation of PET/mpMR resulted in a higher detection rate for local tumor recurrence in the prostatic bed in men with biochemical failure after radical prostatectomy. However, the addition of wbMR to 18F-FCH or 68Ga-PSMA PET did not improve detection of regional or distant metastases..

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 T2 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 T2 and a six b-value diffusion sequence (0, 90, 500, 1500, 2000, 3000 s/mm2 ) 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, A1 , A2 , 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..

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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..

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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_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_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_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_v2. Inter-reader percentage agreement was 83% for subjective Likert-assessment and 56% for PI-RADS_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..

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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..

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..

BACKGROUND: Intratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. PATIENTS AND METHODS: Forty-nine men with elevated prostate-specific antigen and multiparametric-magnetic resonance imaging detected PC underwent image-guided multiregion transperineal biopsy. Seventy-nine tumour regions from 25 patients with PC underwent sequencing, analysis of mutations, copy number and neoepitopes combined with tumour infiltrating T-cell subset quantification. RESULTS: We demonstrated extensive somatic nucleotide variation and somatic copy number alteration heterogeneity in high-risk PC. Overall, the mutational burden was low (0.93/Megabase), but two patients had hypermutation, with loss of mismatch repair (MMR) proteins, MSH2 and MSH6. Somatic copy number alteration burden was higher in patients with metastatic hormone-naive PC (mHNPC) than in those with high-risk localised PC (hrlPC), independent of Gleason grade. Mutations were rarely ubiquitous and mutational frequencies were similar for mHNPC and hrlPC patients. Enrichment of focal 3q26.2 and 3q21.3, regions containing putative metastasis drivers, was seen in mHNPC patients. We found evidence of parallel evolution with three separate clones containing activating mutations of β-catenin in a single patient. We demonstrated extensive intratumoural and intertumoural T-cell heterogeneity and high inflammatory infiltrate in the MMR-deficient (MMRD) patients and the patient with parallel evolution of β-catenin. Analysis of all patients with activating Wnt/β-catenin mutations demonstrated a low CD8+/FOXP3+ ratio, a potential surrogate marker of immune evasion. CONCLUSIONS: The PROGENY (PROstate cancer GENomic heterogeneitY) study provides a diagnostic platform suitable for studying tumour ITH. Genetic aberrations in clinically high-risk PC are associated with altered patterns of immune infiltrate in tumours. Activating mutations of Wnt/β-catenin signalling pathway or MMRD could be considered as potential biomarkers for immunomodulation therapies. CLINICAL TRIALS.GOV IDENTIFIER: NCT02022371..

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..

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..

Advances in information, communication, and computational technologies allow digital volunteer networks formed by concerned publics across the globe to contribute to an effective response to disasters and crises. Digital volunteer networks are event-centric and emergent networks. Currently, the literature is sharply growing in the fields of communication, computer science, emergency management, and geography. This article aims to assess the current status of the literature and suggest a comprehensive conceptual framework of digital volunteer networks in response to disasters and crises. This framework is based on a traditional input–process–output model consisting of three dimensions: the disaster and crisis context, a voluntary response process, and outputs and outcomes. We also discuss challenges of digital volunteer networks for crisis response. This article is expected to contribute to the development of related theories and hypotheses and practical strategies for managing digital volunteer networks. .

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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..

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Large‐scale natural resource conservation initiatives are increasingly adopting a network governance framework to respond to the ecological, social, and political challenges of contemporary environmental governance. A network approach offers new modes of management that allow resource managers and others to transcend a single institution, organization, resource, or landscape and engage in conservation that is multi‐species and multi‐jurisdictional. However, there are challenges to network governance in large‐scale conservation efforts, which we address by focusing on how special interests can capture networks and shape the goals, objectives, and outcomes of initiatives. The term “network capture” is used here to describe an array of strategies that direct the processes and outcomes of large‐scale initiatives in ways that advance a group's positions, concerns, or economic interests. We outline how new stakeholders emerge from these management processes, and how the ease of information sharing can blur stakeholder positions and lead to competing knowledge claims. We conclude by reasserting the benefits of network governance while acknowledging the unique challenges that networks present..

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BACKGROUND: Whilst multi-parametric magnetic resonance imaging (mp-MRI) has been a significant advance in the diagnosis of prostate cancer, scanning all patients with elevated prostate specific antigen (PSA) levels is considered too costly for widespread National Health Service (NHS) use, as the predictive value of PSA levels for significant disease is poor. Despite the fact that novel blood and urine tests are available which may predict aggressive disease better than PSA, they are not routinely employed due to a lack of clinical validity studies. Furthermore approximately 40 % of mp-MRI studies are reported as indeterminate, which can lead to repeat examinations or unnecessary biopsy with associated patient anxiety, discomfort, risk and additional costs. METHODS/DESIGN: We aim to clinically validate a panel of minimally invasive promising blood and urine biomarkers, to better select patients that will benefit from a multiparametric prostate MRI. We will then test whether the performance of the mp-MRI can be improved by the addition of an advanced diffusion-weighted MRI technique, which uses a biophysical model to characterise tissue microstructure called VERDICT; Vascular and Extracellular Restricted Diffusion for Cytometry in Tumours. INNOVATE is a prospective single centre cohort study in 365 patients. mp-MRI will act as the reference standard for the biomarker panel. A clinical outcome based reference standard based on biopsy, mp-MRI and follow-up will be used for VERDICT MRI. DISCUSSION: We expect the combined effect of biomarkers and VERDICT MRI will improve care by better detecting aggressive prostate cancer early and make mp-MRI before biopsy economically viable for universal NHS adoption. TRIAL REGISTRATION: INNOVATE is registered on ClinicalTrials.gov, with reference NCT02689271 ..

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..

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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..

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Contingent knowledge workers will play an increasingly important role in organisational success as workers transition in and out of project‐based innovation teams with more frequency. Our research finds that collaborators in the contingent, high‐skill workforce face uncertainty challenges to their work that are unique from the independent, contingent professionals more often studied. The article proposes a theoretical framework of uncertainty to guide us in understanding collaborative contingent knowledge workers’ work experience. Interviews with postdoctoral researchers reveal four findings about the influence of these highly uncertain work environments on collaborative contingent knowledge workers – collaboration isolation, frustrated independence, performance anxiety and internalised blame. Perhaps most concerning is that the workers internalise the negative impacts as personal failings instead of recognising them as consequences of a poorly designed work environment. This study argues for the need to manage and mitigate different sources of uncertainty to avoid creating an unnecessary burden on contingent knowledge workers, and to enable a sustainable, contingent knowledge workforce..

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Summary The Park Grass Experiment, begun in 1856, is the oldest ecological experiment in existence. Its value to science has changed and grown since it was founded to answer agricultural questions. In recent times the experiment has shown inter alia how: plant species richness, biomass and pH are related; community composition responds to climatic perturbation and nutrient additions; soil is acidified and corrected by liming. It also provided one of the first demonstrations of the evolution of adaptation at a very local scale and contains a putative case of the evolution of reproductive isolation by reinforcement. The application of molecular genetic markers to archived plant material promises to reveal a whole new chapter of genetic detail about the long‐term dynamics of plant populations. Over the range of values observed at Park Grass, biomass (productivity) has a negative effect upon species richness. Any positive effect of species richness on productivity could only be weak by comparison. The experiment provides support for both the competitive exclusion and pool size hypotheses for determination of species density. Instantaneous comparisons of species richness between plots do not accurately reflect temporal rates of loss which may be multiplicative rather than additive. This suggests that comparisons among sites, nutrient inputs, especially N treatments, or soil acidity may in general underestimate the threat posed to plant species diversity by long‐term changes in plant nutrient availability, both enrichment and depletion. Differences between plots at the community level are maintained despite a flow of propagules between plots. There is no strong evidence for a spatial mass effect. Guild (grass/legume/other) compositions of plant communities have equilibrated, but the species composition within guilds is more dynamic and continues to change over time, suggesting that species and guild abundances are independently regulated. At least some members of all the major trophic levels, including predators (spiders), herbivores (leafhoppers) and detritivores (springtails) are treatment‐specific in their distributions. Plant populations on Park Grass are subdivided by treatments which, to some degree, have led to plots becoming genetically isolated from one another and decoupled demographically. This subdivision has created a metapopulation structure in each species, characterized by species‐specific rates of local colonization and extinction. Inverse clines in flowering time occur in the grass Anthoxanthum odoratum across some plot boundaries. These suggest that reproductive isolation between plots has been reinforced by natural selection. Drift as well as selection may have taken place in A. odoratum, especially on plots where effective population size is restricted by population bottlenecks caused by drought. Park Grass illustrates how long‐term experiments grow in value with time and how they may be used to investigate scientific questions that were inconceivable at their inception. This is as likely to be true of the future of Park Grass as it has proved to be of its past. .

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Personalized stories are a powerful tool for communicating about science, particularly when a scientific topic is complex or unfamiliar. One example of such a topic is drought, something many regions of the world face regularly. Like other environmental challenges, drought recovery efforts benefit from a mobilized collective response through prosocial action, including volunteering and donations. The objective of this study was to examine how storytelling about drought influences emotional responses and empathic processes that in turn contribute to prosocial action. Using data collected from an online survey (N= 249) with undergraduate students, the current study tests the hypothesis that, relative to non-personalized stories, personalized news stories about drought will increase audiences' cognitive and emotional responses, including perceived suffering, narrative engagement, and state empathy. In addition, this study examines how emotional responses to personalized news stories influence readers' intentions to donate to farmers suffering from drought. Results reveal that personalized news stories are more likely than non-personalized stories to increase readers' state empathy and perceptions of others' suffering. Perceived suffering was directly related to the affective and cognitive dimensions of state empathy. Narrative engagement (i.e., transportation) was also directly related to the affective and cognitive dimensions of state empathy and indirectly associated with intentions to donate to assist those suffering from drought. Affective state empathy was directly associated with donation intentions, suggesting that an emotional response to media portrayals of suffering may promote prosocial intentions. We discuss the potential implications for using personalized news stories about drought and other natural disasters to motivate prosocial action..

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