Clinical impact of CEUS on non-characterizable observations and observations with intermediate probability of malignancy on CT/MRI in patients at risk for HCC.

BACKGROUND: Hepatocellular carcinoma (HCC) is a unique cancer allowing tumor diagnosis with identification of definitive patterns of enhancement on contrast-enhanced imaging, avoiding invasive biopsy. However, it is still unclear to what extent Contrast-Enhanced Ultrasound (CEUS) is a clinically useful additional step when Computed tomography (CT) or Magnetic resonance imaging (MRI) are inconclusive. METHODS: A prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) was conducted between January 2018 and August 2021. 646 patients at risk for HCC with focal liver lesions were enrolled. CEUS was performed using an intravenous ultrasound contrast agent within 4 weeks of CT/MRI. Liver nodules were categorized based on LI-RADS (LR) criteria. Histology or one-year follow-up CT/MRI imaging results were used as the reference standard. The diagnostic performance of CEUS was evaluated for inconclusive CT/MRI scan in two scenarios for which the AASLD recommends repeat imaging or imaging follow-up: observations deemed non-characterizable (LR-NC) or with indeterminate probability of malignancy (LR-3). RESULTS: 75 observations on CT or MRI were categorized as LR-3 (n = 54) or LR-NC (n = 21) CEUS recategorization of such observations into a different LR category (namely, into one among LR-1, LR-2, LR-5, LR-M, or LR-TIV) resulted in management recommendation changes in 33.3% (25/75) and in all but one (96.0%, 24/25) observation, the new management recommendations were correct. CONCLUSION: CEUS LI-RADS resulted in management recommendations change in substantial number of liver observations with initial indeterminate CT/MRI characterization, identifying both non-malignant lesions and HCC, potentially accelerating the diagnostic process and alleviating the need for biopsy or follow-up imaging. CLINICALTRIALS: gov number, NCT03318380.

Taxanes hypersensitivity is not a risk factor for severe reactions to SARS-CoV-2 vaccines.

Summary: Background. Hypersensitivity reactions (HSR) to taxanes have been related to a complement activation by their excipients, polyoxyethylated castor oil and Polysorbate 80, structurally related to those of SARS-CoV-2 vaccines. The aim of this study was to verify the presence of a higher risk of HSR to SARS-CoV-2 vaccines in patients with history of HSR to taxanes. Methods. Patients with history of HSR to taxanes were evaluated before the vaccination in our center and underwent skin tests for PEG and Polysorbate 80 (PandP). Some patients completed the vaccination course in other centers without prior PandP skin tests because they had not manifested taxanes hypersensitivity before vaccination, or because those tests were not available. Results. 50 patients were evaluated. 100% of patients with history of hypersensitivity to taxanes completed the vaccine course with no cases of anaphylaxis. 33 underwent skin tests for PandP before the vaccination and no correlation was found between the positivity of PandP and taxanes skin tests (p = 0.538). 7 patients developed mild symptoms during skin tests and vaccination, similar but weaker than those suffered at the time of the taxane infusion, independently from the results of skin tests. Conclusions. In our cohort patients with history of reaction to taxanes were not at higher risk to develop anaphylaxis to SARS-CoV-2 vaccines. However, a common non-IgE mediated mechanism behind those HSRs cannot be completely excluded. This can only account for mild and harmless symptoms in case of SARS-CoV-2 vaccines. However, prudence is still recommended in these patients.

Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis.

BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.

Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib.

BACKGROUND: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. PATIENTS AND METHODS: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. RESULTS: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin-bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). CONCLUSION: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.

Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma.

BACKGROUND: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. PATIENTS AND METHODS: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. RESULTS: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. CONCLUSIONS: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC.

Focal nodular hyperplasia: new findings at Doppler ultrasonography.

OBJECTIVE: The aim of our study was to explore the features of focal nodular hyperplasia (FNH) at Doppler ultrasonography, analyzing specifically the presence of intratumoral venous flow in patients with an established diagnosis of FNH. Previous studies showed that using a venous Doppler spectrum, intratumoral vessels are often depicted in hepatocellular adenoma (HCA) but less frequently in FNH. PATIENTS AND METHODS: Forty-five FNHs from thirty-three consecutive patients (26 female, 7 male; mean±SD age: 40±13) underwent color Doppler ultrasonography and spectral analysis according to a standardized protocol. FNH diagnosis was established by the presence of typical behavior at contrast-enhanced ultrasound (CEUS) associated with another imaging technique (contrast-enhanced computed tomography [ceCT] or contrast-enhanced magnetic resonance [ceMR]). A biopsy was performed when imaging was inconclusive. All data concerning Doppler analysis were reviewed by two more operators, blinded to the final diagnosis, and the interobserver agreement for the presence of venous Doppler signal was determined by Cohen's Kappa. RESULTS: Of the 33 patients, 24 had a single solitary focus, and 9 had multiple foci. Lesion diameter ranged between 1.2 and 8.9 cm (mean ± SD 3.2±1.6 cm). The central feeding artery with the typical arterial spectrum was detected in all 45 lesions, whereas the spoke-wheel sign was observed in 18 cases (40%). A venous Doppler signal was detected in 35 FNHs (77.8%), and in 60% of them, it was identified in the center of the lesion. CONCLUSIONS: Venous Doppler signal located in the center of the lesion suspected to be a hypervascular benign lesion cannot be considered a typical HCA feature since it has been detected in a high percentage of FNH cases.

Lenvatinib mesylate to treat hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a worldwide healthcare problem, with a rising incidence. In its advanced stage, the prognosis of untreated HCC is very poor. Only in 2007, after a long series of failed trials, the multi-tyrosine kinase inhibitor sorafenib demonstrated its superiority over placebo, becoming the first approved frontline therapy for advanced HCC. For a decade, all of the frontline trials using sorafenib as a comparator systematically failed, leaving this drug as the only available treatment in this setting. In 2018, lenvatinib mesylate (another multitarget tyrosine kinase inhibitor) demonstrated noninferiority compared to sorafenib in the phase III, randomized, controlled REFLECT trial. Currently, lenvatinib represents the only available alternative to sorafenib as a frontline systemic treatment of advanced HCC. In this monograph, we review the main preclinical and clinical evidence that emerged in the trials of lenvatinib, with particular attention to the features differentiating this drug from sorafenib.

Clinical Impact and Safety of Anticoagulants for Portal Vein Thrombosis in Cirrhosis.

OBJECTIVES: Portal vein thrombosis (PVT) is a frequent complication of cirrhosis. Benefit, safety, and duration of anticoagulant treatment in this setting are controversial issues. The aim of this study was to analyze the course of PVT in a large cohort of cirrhotic patients undergoing or not anticoagulation therapy. METHODS: The data of 182 patients who presented between January 2008 and March 2016 with cirrhosis and PVT with at least 3 months of follow-up after the first PVT detection were analyzed. Eighty-one patients received anticoagulants and 101 were untreated per physician discretion. RESULTS: The extension of the thrombosis decreased by >50% in 46 (56.8%, with complete recanalization in 31/46) patients under anticoagulation and in 26 (25.7%) untreated patients. Of the 46 patients who underwent recanalization, 17 (36%) suffered recurrent thrombosis after stopping anticoagulation therapy. Kaplan-Meier analysis showed a higher survival rate in the treated group (p = 0.010). At multivariate analysis, anticoagulation was an independent factor associated with longer survival (HR:0.30, CI:0.10-0.91, p = 0.014). The Child-Turcotte-Pugh classes B/C negatively influenced survival (hazard ratio, (HR):3.09, confidence interval (CI):1.14-8.36, p = 0.027 for Child-Turcotte-Pugh B and HR:9.27, CI:2.67-32.23, p < 0.001 for Child-Turcotte-Pugh C). Bleeding complications occurred in 22 (21.8%) untreated and 16 (19.7%) treated patients, but in only four cases was it judged to be related to the anticoagulant treatment. No death was reported as a consequence of the bleeding events. CONCLUSIONS: Anticoagulant treatment is a safe and effective treatment leading to partial or complete recanalization of the portal venous system in 56.8% of cases, improving the survival of patients with cirrhosis and PVT. Discontinuation of the therapy is associated with a high rate of PVT recurrence.

Average treatment effect of hepatic resection versus locoregional therapies for hepatocellular carcinoma.

BACKGROUND: When comparing the efficacy of surgical and non-surgical therapies for hepatocellular carcinoma (HCC), a major limitation is the causal inference problem. This concerns the impossibility of seeing both outcomes of two different treatments for the same individual at the same time because one is inevitably missing. This aspect can be addressed methodologically by estimating the so-called average treatment effect (ATE). METHODS: To estimate the ATE of hepatic resection over locoregional therapies for HCC, data from patients treated in two tertiary care settings between August 2000 and December 2014 were used to obtain counterfactual outcomes using an inverse probability weight survival adjustment. RESULTS: A total of 1585 patients were enrolled: 815 underwent hepatic resection, 337 radiofrequency ablation (RFA) and 433 transarterial chemoembolization (TACE). The option of operating on all patients who had tumour ablation returned an ATE of +9·8 months for resection (effect size 0·111; adjusted P = 0·064). The option of operating on all patients who had TACE returned an ATE of +27·9 months (effect size 0·383; adjusted P < 0·001). The ATE of surgery was negligible in patients undergoing ablation for very early HCCs (effect size 0·027; adjusted P = 0·627), independently of albumin-bilirubin (ALBI) grade; or in patients with ALBI liver function grade 2 (effect size 0·083; adjusted P = 0·213), independently of tumour stage. In all other instances, the ATE of surgery was notably greater. Operating on patients who had TACE with multinodular HCC beyond the Milan criteria resulted in a mild ATE (effect size 0·140; adjusted P = 0·037). CONCLUSION: ATE estimation suggests that hepatic resection is a better treatment option than ablation and TACE in patients with HCC.

EFSUMB Statement on Medical Student Education in Ultrasound [long version].

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) recommends that ultrasound should be used systematically as an easy accessible and instructive educational tool in the curriculum of modern medical schools. Medical students should acquire theoretical knowledge of the modality and hands-on training should be implemented and adhere to evidence-based principles. In this paper we report EFSUMB policy statements on medical student education in ultrasound that in a short version is already published in Ultraschall in der Medizin 1.

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part V - EUS-Guided Therapeutic Interventions (short version).

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation (short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part IV - EUS-guided interventions: General Aspects and EUS-guided Sampling (Short Version).

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle-based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (short version; the long version is published online).

Years of life that could be saved from prevention of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour ≥ 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost.

Serum microRNAs as novel biomarkers for primary sclerosing cholangitis and cholangiocarcinoma.

The diagnosis of primary sclerosing cholangitis (PSC) is difficult due to the lack of sensitive and specific biomarkers, as is the early diagnosis of cholangiocarcinoma (CC), a complication of PSC. The aim of this study was to identify specific serum miRNAs as diagnostic biomarkers for PSC and CC. The levels of 667 miRNAs were evaluated in 90 human serum samples (30 PSC, 30 CC and 30 control subjects) to identify disease-associated candidate miRNAs (discovery phase). The deregulated miRNAs were validated in an independent cohort of 140 samples [40 PSC, 40 CC, 20 primary biliary cirrhosis (PBC) and 40 controls]. Receiver operating characteristic (ROC) curves were established and only miRNAs with an area under the curve (AUC) > 0·70 were considered useful as biomarkers. In the discovery phase we identified the following: 21 miRNAs expressed differentially in PSC, 33 in CC and 26 in both in comparison to control subjects as well as 24 miRNAs expressed differentially between PSC and CC. After the validation phase, miR-200c was found to be expressed differentially in PSC versus controls, whereas miR-483-5p and miR-194 showed deregulated expression in CC compared with controls. We also demonstrate a difference in the expression of miR-222 and miR-483-5p in CC versus PSC. Combination of these specific miRNAs further improved the specificity and accuracy of diagnosis. This study provides a basis for the use of miRNAs as biomarkers for the diagnosis of PSC and CC.

Ultrasound Shear Wave Elastography for Liver Disease. A Critical Appraisal of the Many Actors on the Stage.

In the last 12 - 18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan(®) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by transient elastography, performed with Fibroscan(®), a technology dedicated exclusively to liver elastography. Since then, more than 1300 articles dealing with transient elastography have been listed in PubMed, some describing results with more than 10,000 patients 5. The technique has been tested in nearly all liver disease etiologies, with histology as the reference standard. Meta-analysis of data, available in many etiologies 6, showed good performance and reproducibility as well as some situations limiting reliability 5. Thresholds for the different fibrosis stages (F0 to F4) have been provided by many large-scale studies utilizing histology as the reference standard 7. Transient elastography tracks the velocity of shear waves generated by the gentle hit of a piston on the skin, with the resulting compression wave traveling in the liver along its longitudinal axis. The measurement is made in a 4 cm long section of the liver, thus able to average slightly inhomogeneous fibrotic deposition.In 2008 a new modality became available, Acoustic Radiation Force Impulse (ARFI) quantification, and classified by EFSUMB 1 as point shear wave elastography (pSWE), since the speed of the shear wave (perpendicular to the longitudinal axis) is measured in a small region (a "point", few millimeters) at a freely-choosen depth within 8 cm from the skin. This technology was the first to be implemented in a conventional ultrasound scanner by Siemens(®) 8. Several articles have been published regarding this technology, most with the best reference standards 9, some including findings on more than 1000 hepatitis C patients 10 or reporting meta-analysis of data 11. Although the correlation between Siemens pSWE and transient elastography appeared high 12 13, the calculated thresholds for the different fibrosis stages and the stiffness ranges between the two techniques are not superimposable.Interestingly, pSWE appears to provide greater applicability than transient elastography for measuring both liver 13 and spleen stiffness, which is a new application of elastography 14, of interest for the prediction of the degree of portal hypertension 15 16.Nowadays other companies have started producing equipment with pSWE technology, but only very few articles have been published so far, for instance describing the use of Philips(®) equipment, which was the second to provide pSWE. These articles show preliminary good results also in comparison with TE 17 18. Not enough evidence is currently available in the literature about the elastographic performance of the products most recently introduced to the market. Furthermore, with some products the shear wave velocities generated by a single ultrasound acoustic push pulse can be measured in a bidimensional area (a box in the range of 2 - 3 cm per side) rather than in a single small point, producing a so-called bidimensional 2D-SWE 1. The stiffness is depicted in color within the area and refreshing of the measurement occurs every 1 - 2 seconds. Once the best image is acquired, the operator chooses a Region Of Interest (ROI) within the color box, where the mean stiffness is then calculated. 2D-SWE can be performed as a "one shot" technique or as a semi-"real-time" technique for a few seconds (at about 1 frame per second) in order to obtain a stable elastogram. With either technique, there should be no motion/breathing during image acquisition. A bidimensional averaged area should overcome the limitation of pSWE to inadvertently investigate small regions of greater or lesser stiffness than average. A shear wave quality indicator could be useful to provide real-time feedback and optimize placement of the sampling ROIs, a technology recently presented by Toshiba(®), but which is still awaiting validation in the literature.Supersonic Imagine by Aixplorer(®) which works with a different modality of insonation and video analysis compared to the the previously-mentioned three techniques (i. e., transient elastography, pSWE and 2D-SWE), leading to a bidimensional assessment of liver stiffness in real time up to 5 Hz and in larger regions; thus this technique is also termed real-time 2 D SWE. It has been available on the market for a few years 19 20, and many articles have been published showing stiffness values quite similar to those of Fibroscan(®) 21; likewise, defined thresholds based on histological findings have appeared in several articles 19 20 21.After this brief summary of the technological state of the art we would like to mention the following critical issues that we believe every user should note prior to providing liver stiffness reports. · The thresholds obtained from the "oldest" techniques for the various fibrosis stages based on hundreds of patients with histology as reference standard cannot be straightforwardly applied to the new ultrasound elastography techniques, even if based on the same principle (e. g. pSWE). In fact, the different manufacturers apply proprietary patented calculation modes, which might result in slightly to moderately different values. It should be kept in mind that the range for intermediate fibrosis stages (F1 to F3) is quite narrow, in the order of 2 - 3 kilopascal (over a total range spanning 2 to 75 kPa with Fibroscan), so that slightly different differences in outputs could shift the assessment of patients from one stage to another. Comparative studies using phantoms and healthy volunteers, as well as patients, are eagerly awaited. In fact, the equipment might not produce linear correlations of measurements at different degrees of severity of fibrosis. As a theoretical example, some equipment might well correlate in their values with an older technique, such as transient elastography, at low levels of liver fibrosis, but not as well in cases of more advanced fibrosis or vice versa. Consequentely, when elastography data are included in a report, the equipment utilized for the measurement should be clearly specified, and conclusions about the fibrosis stage should be withheld if an insufficient number of comparative studies with solid reference standards are available for that specific equipment.. · Future studies using histology as a reference might be biased in comparison to previous studies, since nowadays fewer patients with chronic hepatitis C or hepatitis B undergo biopsy. In fact, due to wide availability of effective drugs as well as the use of established elastography methods for patients with viral hepatitis, most cases submitted to biopsy today have uncertain etiology or inconsistent and inconclusive clinical data. Therefore, extrapolated thresholds from such inhomogeneous populations applied to more ordinary patients with viral hepatitis might become problematic in the future, although no better solution is currently anticipated. This situation might lead to the adoption of a standard validated elastographic method as reference, but this has to be agreed-upon at an international level.. · Ultrasound elastography embedded in conventional scanners usually allows the choice of where to place the ROI within the color stiffness box and whether to confirm or exclude each single measurement when determining the final value. Thus, the operator has a greater potential to influence the final findings than with Fibroscan®, where these choices are not available. This has to be kept in mind to avoid the possibility that an operator could, even inadvertently, tend to confirm an assumption about that specific patient or to confirm the patient's expectations.. · Quality criteria for the new technologies following transient elastography are absent (depending on the manufacturer) or have not been satisfactorily defined, so that the information potentially inserted in a report cannot currently be judged for its reliability by the clinician.. (ABSTRACT TRUNCATED)

EFSUMB statement on medical student education in ultrasound [short version].

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) recommends that ultrasound should be used systematically as an easy accessible and instructive educational tool in the curriculum of modern medical schools. Medical students should acquire theoretical knowledge of the modality and hands-on training should be implemented and adhere to evidence-based principles. In this paper we summarise EFSUMB policy statements on medical student education in ultrasound.

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part III - Abdominal Treatment Procedures (Short Version).

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, safety and efficacy of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (short version; a long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part VI - Ultrasound-Guided Vascular Interventions.

The sixth part of the Guidelines on Interventional Ultrasound produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for ultrasound guidance and assistance in vascular interventions. Based on convincing data, real-time sonographic guidance for central venous access is strongly recommended as a key safety measure. Systematic analysis of scientific literature shows that in difficult situations and special circumstances US guidance may also improve the efficacy and safety of peripheral venous and arterial access and endovascular interventions. Moreover, the recommendations of this guideline endorse the use of ultrasound to detect complications of vascular access and US-guided interventional treatment of arterial pseudoaneurysms.

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part IV - EUS-guided Interventions: General aspects and EUS-guided sampling (Long Version).

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (long version).