Quantitative time intensity curve analysis of contrast-enhanced ultrasound (CEUS) examinations for the assessment of focal liver lesions.

Contrast enhanced ultrasound (CEUS) is well-established for the characterization of focal liver lesions (FLLs). By using intravenous ultrasound contrast agents, followed by specific low mechanical index examinations, CEUS enables a high spatial and temporal resolution as well as a dynamic assessment of macro- and microvascularization down to the capillaries. Nevertheless, CEUS has the disadvantage of being examiner-dependent, so quantitative analysis of time-intensity curves in dynamic CEUS (D-CEUS) could provide further information. The aim of this article is to provide a general review of the current literature regarding the usefulness of D-CEUS in the assessment of FLLs.

Recombinant Tissue Plasminogen Activator: The New Concept for Dissolving Septae in Loculated Peri-pancreatic Fluid Collection prior to Endoscopic Drainage. A Case Report.

Peri-pancreatic fluid collections are late complications of acute pancreatitis. Loculated peri-pancreatic fluid collections, even rare, remain the "black sheep" in terms of drainage, due to difficulty to puncture all compartments, thus prohibiting proper drainage of all compartments. Recombined tissue plasminogen activator (r-tPA) has been advocated as treatment of the loculated collections, due to its ability to dissolve the fibrinous strands and thus facilitate proper drainage. We report the case of a 58 years-old male presenting with a painful loculated peri-pancreatic fluid collection secondary to acute pancreatitis. We performed Alteplase injection, followed by successful endosonographic drainage with lumen apposing metal stent of the collection after 48 hours. Our observation suggests that r-tPA could be a new strategy for loculated collections management, ensuring better drainage and limiting the indication for surgical treatment.

Safety, Efficacy and Persistence of Advanced Therapies in Inflammatory Bowel Disease: Results from ORIGINS. A Retrospective Observational Study.

BACKGROUND AND AIMS: Real-world assessments of efficacy and safety of advanced therapies used for inflammatory bowel disease (IBD) patients are limited. We aimed to report safety, efficacy and treatment persistence of new molecules (infliximab, adalimumab, vedolizumab, tofacitinib, ustekinumab) in a retrospective multicentric national Romanian analysis. METHODS: We conducted a nationwide, retrospective observational multicentric study. Data were collected retrospectively from electronic and paper files. Patients who started on one of the five investigated molecules during December 2019-December 2021 were included. The main outcome measures were clinical remission, endoscopic healing, persistence on treatment and safety data. RESULTS: A total of 678 adult patients from 24 Romanian IBD centers with a diagnosis of ulcerative colitis or Crohn's disease were included. Participants had previously failure to one (268, 39.5%), two (108, 15%) or more treatment lines and only 38% (259) were biologic naïve. In the 24 months study period, most patients were started on vedolizumab (192, 28%), followed by adalimumab, infliximab, ustekinumab and tofacitinib. In biologic-naïve patients, most physicians (72%) preferred anti-TNF treatment as first line biologic (93 patients started on infliximab, 92 on adalimumab), followed by vedolizumab, ustekinumab and tofacitinib. During follow-up, 71% (470, p=0.05) of patients achieved clinical remission and 36% (134, p=0.03) achieved mucosal healing. The 6 months milestone for persistence was reached in 78% (530) of cases. Almost half of patients (47%, 316 patients) persisted on their current treatment for over 12 months. Overall, an adverse reaction was reported for 67 (10.4%) patients, with no lethal events. CONCLUSIONS: Population of biologic-experienced IBD patients in Romania is increasing and is becoming more difficult to achieve long-term disease control. Discontinuation rates for advanced therapies are high.

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.

Implementation of a Customized Safety Checklist in Gastrointestinal Endoscopy and the Importance of Team Time Out-A Dual-Center Pilot Study.

Background and Objectives: Checking and correctly preparing the patient for endoscopic procedures is a mandatory step for the safety and quality of the interventions. The aim of this paper is to emphasize the importance and necessity of a "team time out" as well as the implementation of a customized "checklist" before the actual procedure. Material and Methods: We developed and implemented a checklist for the safe conduct of endoscopies and for the entire team to thoroughly know about the patient's medical history. The subjects of this study were 15 physicians and 8 endoscopy nurses who performed overall 572 consecutive GI endoscopic procedures during the study period. Results: This is a prospective pilot study performed in the endoscopy unit of two tertiary referral medical centers. We customized a safety checklist that includes the steps to be followed before, during and after the examination. It brings together the whole team participating in the procedure in order to check the key points during the following three vital phases: before the patient falls asleep, before the endoscope is inserted and before the team leaves the examination room. The perception of team communication and teamwork was improved after the introduction of the checklist. The checklist completion rates, identity verification rates of patients by the endoscopist, adequate histological labeling management and explicit recording of follow-up recommendations are some of the parameters that improved post-intervention. Conclusions: Using a checklist and adapting it to local conditions is a high-level recommendation of the Romanian Ministry of Health. In a medical world where safety and quality are essential, a checklist could prevent medical errors, and team time out can ensure high-quality endoscopy, enhance teamwork and offer patients confidence in the medical team.

Performance and Safety of EUS Ablation Techniques for Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis.

BACKGROUND: Pancreatic cystic lesions (PCL) represent an increasingly diagnosed condition with significant burden to patients' lives and medical resources. Endoscopic ultrasound (EUS) ablation techniques have been utilized to treat focal pancreatic lesions. This systematic review with meta-analysis aims to assess the efficacy of EUS ablation on PCL in terms of complete or partial response and safety. METHODS: A systematic search in Medline, Cochrane and Scopus databases was performed in April 2023 for studies assessing the performance of the various EUS ablation techniques. The primary outcome was complete cyst resolution, defined as cyst disappearance in follow-up imaging. Secondary outcomes included partial resolution (reduction in PCL size), and adverse events rate. A subgroup analysis was planned to evaluate the impact of the available ablation techniques (ethanol, ethanol/paclitaxel, radiofrequency ablation (RFA), and lauromacrogol) on the results. Meta-analyses using a random effects model were conducted and the results were reported as percentages with 95% confidence intervals (95%CI). RESULTS: Fifteen studies (840 patients) were eligible for analysis. Complete cyst resolution after EUS ablation was achieved in 44% of cases (95%CI: 31-57; 352/767; I2 = 93.7%), and the respective partial response rate was 30% (95%CI: 20-39; 206/767; I2 = 86.1%). Adverse events were recorded in 14% (95%CI: 8-20; 164/840; I2 = 87.2%) of cases, rated as mild in 10% (95%CI: 5-15; 128/840; I2 = 86.7%), and severe in 4% (95%CI: 3-5; 36/840; I2 = 0%). The subgroup analysis for the primary outcome revealed rates of 70% (95%CI: 64-76; I2 = 42.3%) for ethanol/paclitaxel, 44% (95%CI: 33-54; I2= 0%) for lauromacrogol, 32% (95%CI: 27-36; I2 = 88.4%) for ethanol, and 13% (95%CI: 4-22; I2 = 95.8%) for RFA. Considering adverse events, the ethanol-based subgroup rated the highest percentage (16%; 95%CI: 13-20; I2 = 91.0%). CONCLUSION: EUS ablation of pancreatic cysts provides acceptable rates of complete resolution and a low incidence of severe adverse events, with chemoablative agents yielding higher performance rates.

Robotic Resection of Ectopic Thyroid Tissue of the Mediastinum - Case Report and Literature Review.

Introduction: Ectopic thyroid tissue (ETT) is a rare cause of mediastinal masses, representing less than 1% of all mediastinal tumors (1). ETT could be detected anywhere along the path of the first embryonic descent of the thyroid gland from the primordial foregut floor to its usual pre-tracheal position. ETT mediastinal localization accounts for fewer than 1% of all ectopic thyroid cases (2,3). Various surgical methods for approaching mediastinal masses have been documented in the literature, including median sternotomy, posterolateral thoracotomy, and, video-assisted thoracoscopic surgery (VATS) (4). More recently, robotic-assisted thoracoscopic surgery (RATS) has been proposed for these masses. The aim of this article is to present the use of robotic-assisted thoracoscopic surgery (RATS) for a rare case of a mediastinal ETT. Case presentation: We present the case of a 40-year-old male with no significant medical history who discovered a mediastinal mass on a thoracic CT scan following COVID-19 infection. Symptoms were dysphagia and anterior thoracic pain with cervical extension. Scintigraphy confirmed the presence of ectopic thyroid tissue in the mediastinum as well as a normal cervical thyroid gland. ETT was histologically confirmed by endoscopic ultrasound guided biopsy. Robotic assisted surgery was the chosen approach to surgically treat this mass and the technical details are presented. The mass was extracted through the cervical incision. Total surgical time was 230 minutes, and the blood loss was 60 ml. The patient was discharged after 48 hours with follow up showing a full recovery with no residual pain or respiratory symptoms. Conclusion: Ectopic thyroid tissue (ETT) is a rare cause of mediastinal masses, and the diagnosis is always a challenge. Robotic assisted thoracoscopic surgery was proved to be safe and efficient in this rare case of ETT developed in the superior mediastinum.

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.

Image Fusion Involving Real-Time Transabdominal or Endoscopic Ultrasound for Gastrointestinal Malignancies: Review of Current and Future Applications.

Image fusion of CT, MRI, and PET with endoscopic ultrasound and transabdominal ultrasound can be promising for GI malignancies as it has the potential to allow for a more precise lesion characterization with higher accuracy in tumor detection, staging, and interventional/image guidance. We conducted a literature review to identify the current possibilities of real-time image fusion involving US with a focus on clinical applications in the management of GI malignancies. Liver applications have been the most extensively investigated, either in experimental or commercially available systems. Real-time US fusion imaging of the liver is gaining more acceptance as it enables further diagnosis and interventional therapy of focal liver lesions that are difficult to visualize using conventional B-mode ultrasound. Clinical studies on EUS guided image fusion, to date, are limited. EUS-CT image fusion allowed for easier navigation and profiling of the target tumor and/or surrounding anatomical structure. Image fusion techniques encompassing multiple imaging modalities appear to be feasible and have been observed to increase visualization accuracy during interventional and diagnostic applications.

Assessing Putative Markers of Colorectal Cancer Stem Cells: From Colonoscopy to Gene Expression Profiling.

Cancer stem cells (CSCs) are proposed to be involved in colorectal cancer (CRC) initiation, growth, and metastasis. The aim of our pilot study was to assess possible correlations between the clinicopathological characteristics of CRC patients and CSCs gene expression patterns, in order to provide insight into new methods for patient stratification and targeted therapeutic strategies. Our study involved 60 CRC patients, and the following three specific CSC genes were targeted: PROM1/CD133, ALCAM/CD166 and HCAM /CD44. Data are presented as relative mRNA expression of target genes to GAPDH. The expression of total CD133 and CD166 was assessed in paired samples of CRC tumors and adjacent tissue, while CD44 was assessed in similar samples. The qRT-PCR analysis detected all three targeted genes to different extents, in both normal and tumor tissue. In nine cases (15.69%), total CD133 had a higher expression in tumor tissue, whilst in 28 cases (47.06%) the expression was higher in non-malignant peritumor tissue. The total CD166 expression was increased in tumor tissue compared with paired non-invaded peritumor samples in eight cases (13.73%), whilst in eight cases (13.73%) the expression was higher in non-malignant peritumor tissue. Total CD44 expression was higher in tumor tissue compared with paired non-invaded peritumor samples in 47 cases (78.95%). In the remaining cases the difference between paired samples was biologically insignificant. In conclusion, our study suggests that qRT-PCR is feasible in assessing the gene expression profiles of CSCs from CRC, and a promising pathway to be followed for determining how often a person needs screening by colonoscopy and at which age to start. This could improve CRC diagnosis and early patient stratification, and open the way for new oncologic treatment development.

How to perform EUS-guided biliary drainage.

EUS-guided biliary drainage (EUS-BD) has recently gained widespread acceptance as a minimally invasive alternative method for biliary drainage. Even in experienced endoscopy centers, ERCP may fail due to inaccessibility of the papillary region, altered anatomy (particularly postsurgical alterations), papillary obstruction, or neoplastic gastric outlet obstruction. Biliary cannulation fails at first attempt in 5%-10% of cases even in the absence of these factors. In such cases, alternative options for biliary drainage must be provided since biliary obstruction is responsible for poor quality of life and even reduced survival, particularly due to septic cholangitis. The standard of care in many centers remains percutaneous transhepatic biliary drainage (PTBD). However, despite the high technical success rate with experienced operators, the percutaneous approach is more invasive and associated with poor quality of life. PTBD may result in long-term external catheters for biliary drainage and carry the risk of serious adverse events (SAEs) in up to 10% of patients, including bile leaks, hemorrhage, and sepsis. PTBD following a failed ERCP also requires scheduling a second procedure, resulting in prolonged hospital stay and additional costs. EUS-BD may overcome many of these limitations and offer some distinct advantages in accessing the biliary tree. Current data suggest that EUS-BD is safe and effective when performed by experts, although SAEs have been also reported. Despite the high number of clinical reports and case series, high-quality comparative studies are still lacking. The purpose of this article is to report on the current status of this procedure and to discuss the tools and techniques for EUS-BD in different clinical scenarios.

Quantitative contrast-enhanced endoscopic ultrasound in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors: can we predict survival using perfusion parameters? A pilot study.

AIM: Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) parameters may be used to predict prognosis of pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (pNET). The aim of this study was to investigate the association between several perfusion parameters on CEH-EUS performed before treatment and survival outcome in patients with PDAC or pNET. MATERIAL AND METHODS: Thirty patients with PDAC or pNET who underwent CEH-EUS and EUS-guided fine needle aspiration (EUS-FNA) were included. Quantitative analysis of tumor vascularity was performed using time-intensity curve (TIC) analysis-derived parameters, obtained from processing CEH-EUS recordings with a commercially available software (VueBox). Cox proportional hazards models were used to determine associations with survival outcome. RESULTS: Median overall survival (OS) for PDAC patients was 9.61 months (95% CI: 0.1-38.7) while the median OS for pNET patients was 15.81 months (95% CI: 5.8-24.75. In a multivariate model for OS, a lower peak enhancement (HR=1.76, p=0.02) and a lower wash-in area under the curve (HR=1.06, p=0.001) were associated with worse survival outcome for patients with PDAC. CONCLUSIONS: CEH-EUS parameters may be used as a surrogate to predict PDAC aggressiveness and survival before treatment. After validation by large-scale studies, CEH-EUS perfusion parameters have the potential to be used in pretreatment risk stratification of patients with PDAC and in evidence-based clinical decision support.

Accuracy of Endoscopic Ultrasonography for Gastric Cancer Staging.

Gastric cancer remains a health problem, with treatment indications varying with the TNM stage. We aimed in this study to highlight the role of EUS in GC patients and also to calculate the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of EUS for T and N staging in our group of patients with this disease. In this study, we included 41 GC patients, and individual values for every T stage accuracy, sensitivity, specificity, PPV, NPV, correct staging, understaging, and overstaging were calculated. EUS overall accuracy for T staging was 58.53%, with the highest sensitivity reached for the T4 stage, 95.83%. For N+vs. N-staging, EUS accuracy was 68.29%, with a sensitivity of 75% and a specificity of 44.44%. The positive and negative predicted values for the presence or absence of nodal disease were 82.75%, respectively 33.33%. In conclusion, this study confirmed the importance of EUS for the assessment of GC T and N stage and highlighted the role of this tool in the detection of liver micrometastasis unrevealed by other imaging techniques like abdominal ultrasound or MSCT.

Technical Performance, Overall Accuracy and Complications of EUS-Guided Interventional Procedures: A Dynamic Landscape.

Endoscopic ultrasound (EUS) gained wide acceptance as the diagnostic and minimally invasive therapeutic approach for intra-luminal and extraluminal gastrointestinal, as well as various non-gastrointestinal lesions. Since its introduction, EUS has undergone substantial technological advances. This multi-centric study is a retrospective analysis of a prospectively maintained database of patients who underwent EUS for the evaluation of lesions located within the gastrointestinal tract and the proximal organs. It aimed to extensively assess in dynamic the dual-center EUS experience over the course of the past 20 years. Hence, we performed a population study and an overall assessment of the EUS procedures. The performance of EUS-FNA/FNB in diagnosing pancreatic neoplasms was evaluated. We also investigated the contribution of associating contrast-enhanced ultrasound imaging (CE-EUS) with EUS-FNA/FNB for differentiating solid pancreatic lesions or cystic pancreatic lesions. A total of 2935 patients undergoing EUS between 2002-2021 were included, out of which 1880 were diagnostic EUS and 1052 EUS-FNA/FNB (80% FNA and 20% FNB). Therapeutic procedures performed included endoscopic transmural drainage of pancreatic fluid collections, celiac plexus block and neurolysis, while diagnostic EUS-like CE-EUS (20%) and real-time elastography (12%) were also conducted. Most complications occurred during the first 7 days after EUS-FNA/FNB or pseudocyst drainage. EUS and the additional tools have high technical success rates and low rates of complications. The EUS methods are safe, cost effective and indispensable for the diagnostic or therapeutic management in gastroenterological everyday practice.

Gastric Cancer Angiogenesis Assessment by Dynamic Contrast Harmonic Imaging Endoscopic Ultrasound (CHI-EUS) and Immunohistochemical Analysis-A Feasibility Study.

Tumor vascular perfusion pattern in gastric cancer (GC) may be an important prognostic factor with therapeutic implications. Non-invasive methods such as dynamic contrast harmonic imaging endoscopic ultrasound (CHI-EUS) may provide details about tumor perfusion and could also lay out another perspective for angiogenesis assessment. Methods: We included 34 patients with GC, adenocarcinoma, with CHI-EUS examinations that were performed before any treatment decision. We analyzed eighty video sequences with a dedicated software for quantitative analysis of the vascular patterns of specific regions of interest (ROI). As a result, time-intensity curve (TIC) along with other derived parameters were automatically generated: peak enhancement (PE), rise time (RT), time to peak (TTP), wash-in perfusion index (WiPI), ROI area, and others. We performed CD105 and CD31 immunostaining to calculate the vascular diameter (vd) and the microvascular density (MVD), and the results were compared with CHI-EUS parameters. Results: High statistical correlations (p < 0.05) were observed between TIC analysis parameters MVD and vd CD31. Strong correlations were also found between tumor grade and 7 CHI-EUS parameters, p < 0.005. Conclusions: GC angiogenesis assessment by CHI-EUS is feasible and may be considered for future studies based on TIC analysis.

Professional Standards in Medical Ultrasound - EFSUMB Position Paper (Long Version) - General Aspects.

This first position paper of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) on professional standards presents a common position across the different medical professions within EFSUMB regarding optimal standards for the performing and reporting of ultrasound examinations by any professional ultrasound operator. It describes general aspects of professionality that ensure procedure quality, effectiveness, efficiency, and sustainability in virtually all application fields of medical ultrasound. Recommendations are given related to safety and indication of ultrasound examinations, requirements for examination rooms, structured examination, systematic reporting of results, and management, communication and archiving of ultrasound data. The print version of this article is a short version. The long version is published online.

Professional Standards in Medical Ultrasound - EFSUMB Position Paper (Short Version) - General Aspects.

This first position paper of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) on professional standards presents a common position across the different medical professions within EFSUMB regarding optimal standards for the performing and reporting of ultrasound examinations by any professional ultrasound operator. It describes general aspects of professionality that ensure procedure quality, effectiveness, efficiency, and sustainability in virtually all application fields of medical ultrasound. Recommendations are given related to safety and indication of ultrasound examinations, requirements for examination rooms, structured examination, systematic reporting of results, and management, communication and archiving of ultrasound data. The print version of this article is a short version. The long version is published online.

Gut Microbiota Imbalance in Metastatic Colorectal Patients Treated With EGFRI and Long-Term Antibiotic Therapy for Cutaneous Toxicity: A Pilot Study.

Patients with metastatic colorectal cancer (mCRC) frequently experience epidermal growth factor inhibitors (EGFRI)-induced skin side effects. Antibiotic treatment with doxycycline is often required in order to manage the skin and mucosal toxicity. Since these patients already have significant gut dysbiosis, the long-term antibiotic treatment may destabilize their gut microbiome. Objectives The assessment of intestinal dysbiosis in patients undergoing treatment with EGFRI, who require antibiotic treatment with doxycycline in order to manage adverse skin effects. Methods We conducted a prospective pilot study between 2020 and 2021 involving 10 patients with mCRC. These patients were undergoing treatment with EGFRI and required either short-term or long-term treatment with doxycycline in order to manage skin toxicity. Results The patients with mCRC who were treated with doxycycline for 8 weeks showed overexpression of Escherichia coli, Candida, and Geotrichum species compared to the patients who only received doxycycline treatment for two weeks. Conclusions The elevated levels of Escherichia coli and Candida species in the patients who received doxycycline for eight weeks compared to the patients who received the treatment for two weeks could provide a starting point for the development of a standardized guideline regarding the use of pre-active or reactive antibiotic treatment. We also highlight the importance of analyzing the intestinal microbiome of these patients. The identification of overexpressed species, as well as the deficiency of certain protective species, could guide the administration of probiotics to cover and repair the affected intestinal flora.

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.