The use of simulation in medical ultrasound: Current perspectives on applications and practical implementation (WFUMB state-of-the-art paper).

Simulation has been shown to improve clinical learning outcomes, speed up the learning process, and improve trainee confidence, while taking the pressure off initial face-to-face patient clinical areas. The second part of The World Federation for Ultrasound in Medicine and Biology state-of-the-art paper on the use of simulators provides a general approach on the practical implementation. The importance of needs assessment before developing a simulation-based training program is outlined. We describe the current practical implementation and critically analyze how simulators can be integrated into complex task scenarios to train small or large groups. A wide range of simulation equipment is available especially for those seeking interventional ultrasound training, ranging from animal tissue models, simple synthetic phantoms, to sophisticated high-fidelity simulation platforms using virtual reality. Virtual reality simulators provide feedback and thereby allow trainees to not only to practice their motor skills and hand eye coordination but also to interact with the simulator. Future developments will integrate more elements of automated assessment and artificial intelligence, thereby enabling enhanced realistic training experience and improving skill transfer into clinical practice.

Ablation therapy for patients with colorectal liver metastases with and without extrahepatic metastases: evaluation of long-term outcomes and prognostic factors.

PURPOSE: Ablation is a valuable treatment alternative to surgery for colorectal liver metastases. This study reports the long-term clinical outcomes in patients treated with ablation for colorectal liver metastases with or without extrahepatic metastases. METHODS: Patients with colorectal liver metastases treated with ultrasound-guided ablation at Herlev Hospital, Denmark were included in this retrospective study. RESULTS: This study included 284 patients with 582 metastases. Complete ablation was obtained in 258 patients (91%) evaluated within 6 weeks. During follow-up, 94 patients (33%) developed local recurrence. The median survival for all patients was 31 months, with 1-, 3-, and 5-year survival rates of 82%, 45%, and 21%, respectively. The median survival for patients with extrahepatic metastases (n=49, 17%) was 24 months compared with 33 months for patients without (P=0.142). Propensity score-adjusted Cox regression showed that extrahepatic metastases were associated with increased mortality, with a hazard ratio (HR) of 1.45 (95% confidence interval [CI], 1.02 to 2.05; P=0.039). In multivariate Cox regression analysis for all patients, increased mortality risk was found for a diameter ≥2.6 cm (HR, 1.59; 95% CI, 1.23 to 2.05), >1 metastasis (HR, 1.66; 95% CI, 1.28 to 2.16), and extrahepatic metastases (HR, 1.45; 95% CI, 1.04 to 2.03). Male sex (HR, 0.75; 95% CI, 0.58 to 0.98) and receiving chemotherapy (HR, 0.69; 95% CI, 0.52 to 0.92) were associated with decreased mortality. CONCLUSION: Ablation for colorectal liver metastases offers acceptable survival rates, including for patients with extrahepatic metastases. In addition, chemotherapy was associated with improved survival for both patients with and without extrahepatic metastases.

The ultrasound use of simulators, current view, and perspectives: Requirements and technical aspects (WFUMB state of the art paper).

Simulation has been shown to improve clinical learning outcomes, speed up the learning process and improve learner confidence, whilst initially taking pressure off busy clinical lists. The World Federation for Ultrasound in Medicine and Biology (WFUMB) state of the art paper on the use of simulators in ultrasound education introduces ultrasound simulation, its advantages and challenges. It describes different simulator types, including low and high-fidelity simulators, the requirements and technical aspects of simulators, followed by the clinical applications of ultrasound simulation. The paper discusses the role of ultrasound simulation in ultrasound clinical training, referencing established literature. Requirements for successful ultrasound simulation acceptance into educational structures are explored. Despite being in its infancy, ultrasound simulation already offers a wide range of training opportunities and likely holds the key to a broader point of care ultrasound education for medical students, practicing doctors, and other health care professionals. Despite the drawbacks of simulation, there are also many advantages, which are expanding rapidly as the technology evolves.

Incidental Findings of Gallbladder and Bile Ducts-Management Strategies: General Aspects, Gallbladder Polyps and Gallbladder Wall Thickening-A World Federation of Ultrasound in Medicine and Biology (WFUMB) Position Paper.

The World Federation of Ultrasound in Medicine and Biology (WFUMB) is addressing the issue of incidental findings with a series of position papers to give advice on characterization and management. The biliary system (gallbladder and biliary tree) is the third most frequent site for incidental findings. This first part of the position paper on incidental findings of the biliary system is related to general aspects, gallbladder polyps and other incidental findings of the gallbladder wall. Available evidence on prevalence, diagnostic work-up, malignancy risk, follow-up and treatment is summarized with a special focus on ultrasound techniques. Multiparametric ultrasound features of gallbladder polyps and other incidentally detected gallbladder wall pathologies are described, and their inclusion in assessment of malignancy risk and decision- making on further management is suggested.

Electroporation and Immunotherapy-Unleashing the Abscopal Effect.

The discovery of electroporation in 1968 has led to the development of electrochemotherapy (ECT) and irreversible electroporation (IRE). ECT and IRE have been established as treatments of cutaneous and subcutaneous tumors and locally advanced pancreatic cancer, respectively. Interestingly, the treatment modalities have been shown to elicit immunogenic cell death, which in turn can induce an immune response towards the tumor cells. With the dawn of the immunotherapy era, the potential of combining ECT and IRE with immunotherapy has led to the launch of numerous studies. Data from the first clinical trials are promising, and new combination regimes might change the way we treat tumors characterized by low immunogenicity and high levels of immunosuppression, such as melanoma and pancreatic cancer. In this review we will give an introduction to ECT and IRE and discuss the impact on the immune system. Additionally, we will present the results of clinical and preclinical trials, investigating the combination of electroporation modalities and immunotherapy.

History of Ultrasound in Medicine from its birth to date (2022), on occasion of the 50 Years Anniversary of EFSUMB. A publication of the European Federation of Societies for Ultrasound In Medicine and Biology (EFSUMB), designed to record the historical development of medical ultrasound.

The history of the European Federation of Societies in Ultrasound in Medicine and Biology (EFSUMB) is closely related to the general history of ultrasound. In the presented paper the physical background and history of technologies including A-mode, Time motion or M-mode, 2D Imaging (B-mode) are summarized. In addition, ultrasound tissue characterization, Doppler ultrasound, 3D and 4D ultrasound, intracavitary and endoscopic ultrasound, interventional ultrasound, ultrasonic therapy, contrast enhanced ultrasound (CEUS) and key developments in echocardiography are discussed.

Randomized Phase II Study of Nivolumab With or Without Ipilimumab Combined With Stereotactic Body Radiotherapy for Refractory Metastatic Pancreatic Cancer (CheckPAC).

PURPOSE: To evaluate the clinical benefit of nivolumab with or without ipilimumab in combination with stereotactic body radiotherapy (SBRT) in patients with refractory metastatic pancreatic cancer (mPC). METHODS: Between November 2016 and December 2019, patients with refractory mPC were randomly assigned 1:1 to SBRT of 15 Gy with nivolumab or nivolumab/ipilimumab stratified by performance status (ClinicalTrials.gov identifier: NCT02866383). The primary end point was the clinical benefit rate (CBR), defined as the percentage of patients with complete or partial response (PR) or stable disease, according to RECIST 1.1. Simon's 2-stage phase II optimal design was used independently for both arms, with CBR determining expansion to the second stage. Secondary end points included safety, response rate, duration of response, progression-free survival, and overall survival. Exploratory analyses included biomarkers related to the benefits. RESULTS: Eighty-four patients (41 SBRT/nivolumab and 43 SBRT/nivolumab/ipilimumab) received at least one dose of study treatment. CBR was 17.1% (8.0 to 30.6) for patients receiving SBRT/nivolumab and 37.2% (24.0 to 52.1) for SBRT/nivolumab/ipilimumab. PR was observed in one patient receiving SBRT/nivolumab and lasted for 4.6 months. Six patients receiving SBRT/nivolumab/ipilimumab achieved a PR with a median duration of response of 5.4 months (4.2 to not reached). Grade 3 or higher treatment-related adverse events occurred in 10 (24.4%) and 13 (30.2%) patients in the SBRT/nivolumab and SBRT/nivolumab/ipilimumab groups, respectively. Programmed cell death ligand-1 expression by tumor proportion score or combined positivity score of ≥ 1% was not associated with clinical benefits. On-treatment decreased serum interleukin-6, interleukin-8, and C-reactive protein levels were associated with better overall survival. CONCLUSION: Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with SBRT/nivolumab/ipilimumab in patients with refractory mPC. However, the contribution from SBRT is unknown. Further studies are warranted.

Using Immersive Virtual Reality Simulation to Ensure Competence in Contrast-Enhanced Ultrasound.

Contrast-enhanced ultrasound (CEUS) is used in various medical specialties as a diagnostic imaging tool and for procedural guidance. Experience in the procedure is currently attained via supervised clinical practice that is challenged by patient availability and risks. Prior simulation-based training and subsequent assessment could improve and ensure competence before performance on patients, but no simulator currently exists. Immersive virtual reality (IVR) is a new promising simulation tool that can replicate complex interactions and environments that are unfeasible to achieve by traditional simulators. This study was aimed at developing an IVR simulation-based test for core CEUS competencies and gathering validity evidence for the test in accordance with Messick's framework. The test was developed by IVR software specialists and clinical experts in CEUS and medical education and imitated a CEUS examination of a patient with a focal liver lesion with emphasis on the pre-contrast preparations. Twenty-five medical doctors with varying CEUS experience were recruited as test participants, and their results were used to analyze test quality and to establish a pass/fail standard. The final test of 23 test items had good internal reliability (Cronbach's α = 0.85) and discriminatory abilities. The risks of false positives and negatives (9.1% and 23.6%, respectively) were acceptable for the test to be used as a certification tool prior to supervised clinical training in CEUS.

Contrast enhancement for ultrasound-guided interventions: when to use it and what to expect?

The use of contrast-enhanced ultrasonography (CEUS) has recently become synonymous with high-standard ultrasonography (US). From expanding the reach of US diagnostics to improving the precision of various invasive procedures, CEUS is rapidly becoming a standard in numerous niches. However, proficiency in CEUS comes with a cost, both from a learning curve and material standpoint, and as every growing field, lacks firm evidence and standardization. Therefore, in the current paper, we aim to provide an evidence-based review of available methods and to discuss the advantages and pitfalls of CEUS in interventional procedures, trying to provide strong evidence whenever available, or at least an educated expert opinion if data are lacking.

Clinical Applications of Contrast-Enhanced Thoracic Ultrasound (CETUS) Compared to Standard Reference Tests: A Systematic Review.

INTRODUCTION: Contrast-enhanced ultrasound is utilized in an increasing array of medical fields, including thoracic medicine. However, the technique is still relatively new and only sporadically mentioned in current guidelines and recommendations. The aim of this systematic review is to provide a literature overview and to critically appraise the current clinical applications of contrast-enhanced thoracic ultrasound (CETUS). MATERIALS AND METHODS: A systematic literature search using major electronic databases and in accordance with PRISMA guidelines was performed. Studies with a primary focus on CETUS of thoracic disorders compared to a standard reference test were included. The QUADAS-2 tool was used for quality assessment of the studies. RESULTS: The search identified 43 articles: 1 randomized controlled study, 6 non-randomized controlled studies, 16 non-randomized non-controlled studies, 5 case series, 10 single case reports, and 5 animal studies. The overall risk of bias was judged to be high. Diagnostic accuracy measurements of noninvasive applications of CETUS were only reported in a few studies and they were too dissimilar for meta-analysis. Six studies compared CETUS-guided versus ultrasound-guided transthoracic needle biopsy of thoracic masses. They individually reported a significant increase in diagnostic accuracy in favor of CETUS guidance but were too heterogeneous for meta-analysis. CONCLUSION: The current literature on CETUS is overall heterogeneous with a few high evidence level studies, small study populations and a high risk of bias. CETUS-guided biopsy is the most frequent clinical application and increases diagnostic accuracy compared to ultrasound guidance by an average of 14.6 percentage points.

Managing Incidental Findings Reported by Medical, Sonography and Other Students Performing Educational Ultrasound Examinations.

The evolution of ultrasound imaging into a key technology for diagnostic practice has resulted in its incorporation into the education of medical students worldwide. Although the introduction of ultrasound into medical schools' curricula is relatively recent, training of sonographers and other ultrasound users is mature. Ultrasound is being used in a variety of learning environments and clinical settings, from courses in anatomy and physiology to clinical rotations where medical and other students may scan healthy volunteers or patients, sometimes with little to no supervision. Educators may be apprehensive about a perceived high likelihood that students will encounter unexpected findings during these sessions, which could distress the patient or ultrasound model as well as the student, and result in problems that would be more pronounced if such incidental findings are complex. Policies are needed to address how to manage incidental ultrasound findings that are identified during educational activities. This article summarizes the background and provides a framework for establishing and implementing a well-designed and thoughtful approach for dealing with incidental findings observed in volunteer subjects by medical students during training courses in ultrasound diagnostic scanning. Subject confidentiality should be respected, and review of incidental findings should be transparent without provoking unnecessary anxiety. It is the responsibility of the instructor or supervisor to ensure adequate clinical follow-up if indicated.

Development of and Gathering Validity Evidence for a Theoretical Test in Contrast-Enhanced Ultrasound.

Contrast-enhanced ultrasound (CEUS) is an imaging modality applied in a broad field of medical specialties for diagnostic uses, guidance during biopsy procedures and ablation therapies and sonoporation therapy. Appropriate training and assessment of theoretical and practical competencies are recommended before practicing CEUS, but no validated assessment tools exist. This study was aimed at developing a theoretical multiple-choice question-based test for core CEUS competencies and gathering validity evidence for the test. An expert team developed the test via a Delphi process. The test was administered to medical doctors with varying CEUS experience, and the results were used to evaluate test items, internal-consistency reliability, ability to distinguish between different proficiency levels and to establish a pass/fail score. Validity evidence was gathered according to Messick's framework. The final test with 47 test items could distinguish between operators with and without CEUS experience with acceptable reliability. The pass/fail score led to considerable risk of false positives and negatives. The test may be used as an entry test before learning practical CEUS competencies but is not recommended for certification purposes because of the risk of false positives and negatives.

The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid.

The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.

Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver - Update 2020 - WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS.

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS), first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications.The 2012 guideline requires updating as previously the differences of the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including the United States Food and Drug Administration (FDA) approval as well as the extensive Asian experience, to produce a truly international perspective.These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCA) and are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis to improve the management of patients.

Guidelines and Good Clinical Practice Recommendations for Contrast-Enhanced Ultrasound (CEUS) in the Liver-Update 2020 WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS.

The present, updated document describes the fourth iteration of recommendations for the hepatic use of contrast-enhanced ultrasound, first initiated in 2004 by the European Federation of Societies for Ultrasound in Medicine and Biology. The previous updated editions of the guidelines reflected changes in the available contrast agents and updated the guidelines not only for hepatic but also for non-hepatic applications. The 2012 guideline requires updating as, previously, the differences in the contrast agents were not precisely described and the differences in contrast phases as well as handling were not clearly indicated. In addition, more evidence has been published for all contrast agents. The update also reflects the most recent developments in contrast agents, including U.S. Food and Drug Administration approval and the extensive Asian experience, to produce a truly international perspective. These guidelines and recommendations provide general advice on the use of ultrasound contrast agents (UCAs) and are intended to create standard protocols for the use and administration of UCAs in liver applications on an international basis to improve the management of patients.

Contrast-Enhanced Ultrasound: Development of Syllabus for Core Theoretical and Practical Competencies.

Contrast-enhanced ultrasound (CEUS) is dependent on the observer's competencies, and thus, appropriate education and testing of individual competency is essential. The current international curriculum in CEUS is methodologically weak and lacks validated competency assessment tests. In this study, we aimed to develop a syllabus for core competencies in CEUS using the Delphi process and an international panel of experts. A core writing group constructed an initial draft of the syllabus based on the existing literature. Eight international experts in CEUS or medical education were recruited as Delphi panelists. The draft underwent iterative and anonymous Delphi rounds until a pre-defined level of consensus was reached. The final syllabus consisted of 16 items, which were indexed in two main domains and in procedural order. An expert-generated proposal for a syllabus of core CEUS competencies has been constructed via the Delphi process and may serve as framework for future development of a CEUS curriculum, including competency assessment tests.

Medical Student Ultrasound Education, a WFUMB Position Paper, Part II. A consensus statement of ultrasound societies.

Ultrasound is becoming a fundamental first-line diagnostic tool for most medical specialties and an innovative tool to teach anatomy, physiology and pathophysiology to undergraduate and graduate students. However, availability of structured training programs during medical school is lagging behind and many physicians still acquire all their ultrasound skills during postgraduate training.There is wide variation in medical student ultrasound education worldwide. Sharing successful educational strategies from early adopter medical schools and learning from leading education programs should advance the integration of ultrasound into the university medical school curricula. In this overview, we present current approaches and suggestions by ultrasound societies concerning medical student educa-tion throughout the world. Based on these examples, we formulate a consensus statement with suggestions on how to integrate ultrasound teaching into the preclinical and clinical medical curricula.