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Immune dysregulation and inflammation by hepatic-resident leukocytes is considered a key step in disease progression of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis toward cirrhosis and hepatocellular carcinoma. Here, we provide a protocol for isolation and characterization of liver-resident immune cells from fine-needle biopsies obtained from a rodent model and humans. We describe steps for isolating leukocytes, cell sorting, and RNA extraction and sequencing. We then detail procedures for low-input mRNA sequencing analyses., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We describe the spatial distribution of Echinococcus multilocularis in its main definitive host, the red fox, and the distribution of human cases of alveolar echinococcosis (AE) within a highly endemic focus in southern Germany (13.7-19.9/100,000 in 1992-2018). Human cases were unequally distributed within the endemicity focus. The purpose of the study was to test whether this is reflected in the small-scale distribution of E. multilocularis in foxes., Methods: Three areas with contrasting numbers of human cases were selected within the counties of Ravensburg and Alb-Donau, Baden-Württemberg, Germany. From 2018 to 2020, a total of 240 fox carcasses were obtained from traditional hunters in these areas. Carcasses were necropsied and examined for the presence of intestinal helminths. The statistical analysis was performed with SAS version 9.4, and the geo-mapping with QGIS version 3.16.0 Hannover., Results: The prevalence of E. multilocularis in foxes was 44/106 (41.5%) in area I (commune Leutkirch and environs), 30/59 (50.8%) in area II (commune Isny and environs), and 31/75 (41.3%) in area III (commune Ehingen and environs). From 1992 to 2018, a total of nine human cases of alveolar echinococcosis were recorded in area I, five cases were recorded in study area III, and no cases were recorded in area II. No statistically significant differences between the areas were observed (P > 0.05) for intestinal infections with E. multilocularis, and no apparent spatial correlation with the small-scale distribution of human cases was found. Concerning other zoonotic helminths, Toxocara spp. were equally common, with prevalence of 38.7%, 47.4% and 48.0%, respectively, while the frequency of Alaria alata varied among the study areas (0.0-9.4%), probably reflecting the specific habitat requirements for the establishment of its complex life cycle., Conclusions: Echinococcus multilocularis is highly prevalent in foxes in all the studied areas. The varying number of human AE cases within these areas should therefore be caused by factors other than the intensity of parasite transmission in foxes., (© 2023. The Author(s).)

Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification., (© 2023. The Author(s).)

Purpose: The purpose of this study was to analyze the diagnostic workflow of patients with alveolar echinococcosis (AE) and to identify possible diagnosis-delaying factors., Methods: The number and type of diagnostic procedures of patients diagnosed with alveolar echinococcosis were investigated. The disease history was recorded on the basis of questionnaires, the available findings, and data supplements from the hospital information system (SAP). Statistical analyses were performed using SAS version 9.4 and Microsoft Excel version 16.43. The study population of the cross-sectional study included n = 109 patients with confirmed alveolar echinococcosis., Results: The definitive diagnosis of alveolar echinococcosis of the liver was made at 26.5 ± 65.0 (mean ± standard deviation) months (min - max: 0 - 344, median = 3). The majority of patients were diagnosed because of incidental imaging findings of the liver (n = 74/109 (67.9%)). A total of n = 56/74 (75.7%) of all incidental findings were diagnosed in an outpatient setting, while n = 15/74 (20.3%) of cases were diagnosed during inpatient hospitalization. On average, 1.1 ± 1.2 (0-11, median = 1) ionizing imaging modalities were used for each patient. Contrast-enhanced sonography was received by 0.3 ± 0.5 (0-2, median = 0) patients. Almost all patients (n = 104/109 (95.4%) had at least one suspected hepatic or extrahepatic malignancy at some time. Exclusion of suspected malignancy occurred at a mean of 4.1 ± 16.5 months (0 -133.8, median = 1)., Conclusions: The diagnostic clarification process of AE patients is lengthy and stressful. The psychological burden of a questionable malignant diagnosis is considerable. Early use of contrast-enhanced sonography and, if necessary, puncture of unclear hepatic masses helps to shorten the difficult diagnostic process., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Ultrasonography is an imaging modality of great importance in everyday clinical practice. Technical innovations continuously expand the diagnostic and therapeutic possibilities of ultrasonography requiring continuous upskilling of sonographers. Only a small number of practitioners, in hospital and practice settings in Germany, currently have the required level of skills. Therefore, these techniques are not as readily available as would be desirable. A modern high-end ultrasound scanner in the hands of a qualified sonographer is a diagnostic high-tech precision instrument, which can compete with any other imaging modality.In conclusion, basic sonography, as it is currently practised should be separated from high-end sonography, requiring extensive training and better remuneration. In this context the introduction of a new medical board speciality for ultrasonography, "Advanced Ultrasonography", with corresponding upgrading should be recommended for high-end sonography., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Goal of the Study: Alveolar echinococcosis (AE) is a rare parasitosis caused by the pathogen Echinococcus multilocularis . There is an increase in the number of cases in many countries. The aim of the study was to investigate the current prevalence and the change in the geographical distribution pattern., Methodology: Data were collected retrospectively for the period 1992-2018 using the registered cases in the national disease register for AE in Germany. Statistical analysis was performed using the SAS statistical analysis system version 9.4 (SAS Institute, Cary, N.C., USA)., Results: The study population of n=569 patients included n=322 (56,59%) women and n=247 (43,40%) men. The mean average age of patients with alveolar echinococcosis at first presentation was 53,90±17,54 years (median: 56,00 years). The Moran's I test statistic showed a positive spatial autocorrelation for the period 1992-2018 corresponding to a heterogeneous distribution of disease cases in Germany (I=0,4165; Z=10,9591, p=0,001). An increase in age- and sex-specific prevalence could be determined for the entire study period (1992-2018). The overall prevalence in the period 1992-2018 was 0,71 cases per 100,000 population. The determination of the prevalence for the period 1992-2018 resulted in 0,31 cases for men and 0,40 cases for women per 100,000 population. In the period 1992-1996, no AE cases had been registered in 11/16 (68,8%) federal states (Berlin, Brandenburg, Bremen, Hamburg, Mecklenburg-Vorpommern, Rheinland-Pfalz, Saarland, Sachsen, Sachsen-Anhalt, Schleswig-Holstein und Thüringen). The evaluation recently shows an increased occurrence of cases in the federal states of Hessen, Rheinland-Pfalz and Nordrhein-Westfalen., Conclusions: The analysis shows a rise in prevalence and an increasing number of cases outside the classic endemic areas of Baden-Württemberg and Bavaria., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: Hepatic alveolar echinococcosis (HAE) of the metastasis-like pattern, according to the Echinococcus Ulm classification, is usually discovered as an incidental finding, and the diagnostic differentiation from "true metastases" is difficult. The aim of this study was to investigate whether lesions of the "metastasis-like pattern" in HAE show a typical contrast behavior that can be used for differentiation from metastasis in malignancies., Methods: This prospective clinical study included 11 patients with histologically confirmed HAE of the metastasis-like pattern (7 female and 4 male; mean age, 57.1 years; mean disease duration, 59.5 months), who had been examined by B-scan sonography and CEUS, from the National Echinococcosis Registry Germany., Results: On contrast-enhanced sonography, 11/11 reference lesions showed annular rim enhancement in the arterial and portal venous phases. Throughout the entire 4-min study period, none of the reference lesions showed central contrast enhancement-i.e., all exhibited a complete "black hole sign". A small central scar was seen in 81.8% of cases., Conclusion: In clinically unremarkable patients with incidentally detected metastasis-like lesions of the liver, contrast-enhanced sonographic detection of rim enhancement without central contrast uptake (black hole sign) should be considered evidence supporting a diagnosis of hepatic alveolar echinococcosis with a rare metastasis-like pattern. This can help to differentiate HAE from metastases, especially in high-endemic areas., (© 2022. The Author(s).)

Purpose: Echinococcus multilocularis infects humans as a false intermediate host, primarily with intrahepatic manifestation. Incorrect diagnostic interpretation of these liver tumors, especially the hemangioma-like pattern, can lead to progressive disease. The aim of the study was to investigate the differentiation of typical hemangioma and a hemangioma-like pattern of E. multilocularis using contrast-enhanced ultrasound (CEUS)., Methods: This prospective clinical pilot study comprised patients with hemangioma (n = 14) and patients with alveolar echinococcosis (AE) and hemangioma-like pattern (n = 7). Inclusion criteria were the detection of a liver lesion according to a hemangioma-like pattern on E. multilocularis Ulm classification-ultrasound (EMUC-US) and "confirmed" or "probable" AE according to WHO case definition. The comparison group had hepatic hemangioma with typical B-scan sonographic morphology. All participants underwent conventional and contrast-enhanced ultrasonography., Results: The patient group comprised five men (71.4%) and two women (28.6%) with a mean average age of 64.1 ± 11.2 years. The patient group with hemangioma comprised nine female subjects (64.3%) and five male subjects (35.7%) with a mean average age of 56.1 ± 12.0 years. Early arterial bulbous ring enhancement (p < 0.0001) and iris diaphragm phenomenon could only be visualized in the patients with hemangioma (p < 0.0001). Furthermore, the patients with hemangioma exhibited hyperenhancement in the late phase (p = 0.0003). In contrast, the patients exhibited typical early arterial rim enhancement (p < 0.0001) and, in the portal venous and late phase, complete or incomplete non-enhancement (black hole sign; p = 0.0004)., Conslusion: The behavior of hemangioma-like AE lesions and typical liver hemangiomas is significantly different on CEUS. AE should be considered as a possible differential diagnosis, especially in high-endemic areas., (© 2022. The Author(s).)

Background: In patients with history of malignancy, new-onset liver lesions often present diagnostic challenges. We present the case of a patient with history of neuroendocrine tumor and new-onset echo-rich hepatic lesion, in whom attenuation imaging helped to make the diagnosis. Attenuation imaging is an ultrasound-based technique that allows for the quantification of hepatic fat content on the basis of a measurement of sound attenuation., Case Presentation: We present the case of a 62-year-old Caucasian female patient who underwent pylorus-preserving pancreaticoduodenectomy Whipple surgery in 2004 for histologically well-differentiated neuroendocrine tumor with a proliferation rate of 3% of the pancreatic head. During the course, single liver metastases were resected in 2009, 2010, and 2013. In 2019, hemihepatectomy was performed when two liver metastases recurred. The liver metastases each showed a proliferation rate of 10% with vigorous expression of chromogranin A, synaptophysin, and somatostatin. The most recent follow-up examinations showed a normal chromogranin A value and the patient reported a good general condition. However, sonography revealed a blurred, echoic lesion in the liver. On contrast-enhanced sonography, the lesion showed identical behavior to the surrounding liver parenchyma. In the asymptomatic patient, liver biopsy did not seem to be indicated at the current time. Measurement of the attenuation coefficient by attenuation imaging showed a significantly higher measurement in the area of the echo-rich lesion than in the rest of the liver. The overall findings are consistent with focal fat deposition., Conclusions: Attenuation imaging appears to be useful in the evaluation of unclear echo-rich liver lesions. In particular, primary non-malignant-appearing liver lesions that are unremarkable on abdominal contrast-enhanced ultrasound can be more accurately assessed., (© 2023. The Author(s).)

Pathogenic variants in more than 14 genes have been implicated in monogenic diabetes; however, a significant fraction of individuals with young-onset diabetes and a strong family history of diabetes have unknown genetic etiology. To identify novel pathogenic alleles for monogenic diabetes, we performed whole-genome sequencing (WGS) on four related individuals with type 2 diabetes - including one individual diagnosed at the age of 31 years - that were negative for mutations in known monogenic diabetes genes. The individuals were ascertained from a large case-control study and had a multi-generation family history of diabetes. Identity-by-descent (IBD) analysis revealed that the four individuals represent two sib-pairs that are third-degree relatives. A novel missense mutation (p.P81S) in the PAX6 gene was one of eight rare coding variants across the genome shared IBD by all individuals and was inherited from affected mothers in both sib-pairs. The mutation affects a highly conserved amino acid located in the paired-domain of PAX6 - a hotspot for missense mutations that cause aniridia and other eye abnormalities. However, no eye-related phenotype was observed in any individual. The well-established functional role of PAX6 in glucose-induced insulin secretion and the co-segregation of diabetes in families with aniridia provide compelling support for the pathogenicity of this mutation for diabetes. The mutation could be classified as "likely pathogenic" with a posterior probability of 0.975 according to the ACMG/AMP guidelines. This is the first PAX6 missense mutation that is likely pathogenic for autosomal-dominant adult-onset diabetes without eye abnormalities., (© 2022. The Author(s).)

Competing Interests: The authors declare that they have no conflict of interest.

Pancreatic cystic lesions are a frequent incidental finding in abdominal imaging. Despite its usually benign background, a small fraction exhibiting features suspicious for cancerous development demands continuous follow-up or surgical removal. Current guidelines advocate magnetic resonance imaging and endoscopic ultrasound to evaluate the risk of malignancy, whereas transabdominal ultrasound is perceived as subordinate imaging. The objective of this study was to analyze cyst detection rates of latest-generation ultrasound machines compared to magnetic resonance imaging, computed tomography, and endosonographic ultrasound and to determine inter-rater reliability. The results showed that large cysts facilitate their visualization by transabdominal ultrasound while detection rates are independent of the anatomical part of the pancreas in which they were sited. Changes in the pancreatic duct width, a connection to the pancreatic duct system, and the architectural characteristics of cysts are poorly recognized by transabdominal ultrasound compared to magnetic resonance imaging and endoscopic ultrasound. Computed tomography imaging is preferred over transabdominal ultrasound to detect calcifications and regional lymphadenopathy. Even if conducted by experienced investigators, transabdominal ultrasound examinations fail to agree with magnetic resonance imaging scans regarding cyst detection rates (κ = 0.093)., Competing Interests: The authors declare no conflict of interest.

Background: As part of a prospective clinical study, the degree of hepatic fatty degeneration was quantified in a patient population with nonalcoholic fatty liver disease and sonographically diagnosed with hepatic steatosis using attenuation imaging., Methods: A total of 113 patients with hepatic steatosis were examined, of whom 35 showed focal fatty sparing. Patients with the condition after right nephrectomy, other known liver diseases, and relevant alcohol consumption were excluded from the evaluation. B-scan sonography and sonographic quantification of steatosis content using attenuation imaging (Aplio i800 Canon Medical Systems) were performed. Attenuation imaging is a new ultrasound-based measurement technique that allows objective detection and quantification of hepatic steatosis., Results: The prevalence of focal fatty sparing was 31.0% in the patient population examined. Patients with focal fatty sparing showed a statistically significantly higher attenuation coefficient in contrast to patients without focal fatty sparing (0.79 ± 0.10 vs. 0.66 ± 0.09 dB/cm/MHz, p < 0.0001)., Conclusion: Detection of focal fatty sparing is associated with an increased attenuation coefficient and is thus an expression of higher-grade hepatic fatty degeneration. Patients with focal fatty sparing are more often male and have a higher BMI and a larger liver than patients with nonalcoholic fatty liver disease without focal fatty sparing., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Assessment of hepatic venous pressure gradient (HVPG) is the most reliable, though invasive method for evaluation of portal hypertension. Non-invasive, elastography-based techniques are well established in diagnosis, but not in monitoring of portal hypertension. The aim of our prospective study was to determine the value of acoustic radiation force impulse (ARFI) elastography technique of the liver and spleen in diagnosis and monitoring of portal hypertension., Methods: We prospectively assessed portal hypertension by HVPG and corresponding elastography of the liver and spleen in 31 patients with liver cirrhosis and an indication for primary prophylaxis by non-cardio selective beta-blockers. Investigations were performed at baseline and a follow-up visit after 6-8 weeks. To address the known large variability of values for spleen elastography, well-defined corresponding areas in the spleen were used for baseline and follow-up elastography. Sensitivity, specificity, and AUC-ROC values for both spleen and liver elastography monitoring of portal hypertension were calculated., Results: Liver but not spleen elastography significantly correlated with HVPG results and was suitable for initial evaluation of portal hypertension. However, changes in HVPG results did not show any correlation with alterations of ARFI values from baseline to follow-up visits both for liver and spleen elastography. Spleen stiffness results were not homogeneous across the whole organ differing significantly between the upper, hilar, and bottom placed investigation areas., Conclusions: In this prospective study ARFI-based assessment of liver elastography showed itself suitable for initial assessment but not for monitoring of portal hypertension. Spleen elastography was not appropriate for both, evaluation and monitoring of portal hypertension. A possible explanation for this new data that are in some contrast to previously published results is the degree of portal hypertension in our study, a comparatively short follow-up period, and well-defined investigation areas for spleen elastography in repetitive ARFI investigations. This trial is registered with NCT03315767., Competing Interests: All authors have no conflicts of interest to disclose., (Copyright © 2022 Andreas Binzberger et al.)

Human alveolar echinococcosis is caused by the parasite Echinococcus multilocularis, and dog ownership has been identified as a risk factor. We sought to specify the factors of dog ownership underlying this risk by conducting a case-control study among dog owners in Germany. The analysis revealed an increased odds ratio of ≈7-fold for dog owners whose dogs roam unattended in fields, 13-fold for dog owners who feed their dogs organic waste daily, 4-fold for dog owners who take their dog to a veterinarian only in case of illness, and 10-fold for dog owners who have never been informed by a veterinarian about the risk for infection. The results highlight the risk for infection associated with various factors of dog ownership and the value of veterinarians informing owners about prevention.

Background: While for individuals with obesity an association between hyperleptinemia and an increased risk of non-alcoholic fatty liver disease (NAFLD) is assumed, a leptin deficiency is also related to the development of NAFLD early in life in ob/ob mice, in patients with leptin deficiency due to biallelic likely pathogenic variants in the leptin gene, and in patients with lipodystrophy., Objectives: To investigate the association of circulating leptin levels in pre-pubertal children with obesity and steatosis hepatis., Methods: The cross-sectional study consisted data of n=97 (n male =76) pre-pubertal children (11.8 ± 1.5 years) with obesity (BMIz: 2.4 ± 0.4). Fasting concentrations of cardiometabolic parameters were measured: insulin, c-peptide, glucose, triglyceride, cholesterol, HDL, LDL, AST, ALT, GGT, leptin. Steatosis hepatis was diagnosed by an ultrasound examination (mild, moderate or severe). Patients were categorized into two groups: low z-score of circulating leptin levels (≤25th percentile) vs. normal z-score of circulating leptin levels., Results: One-third of the children with obesity were diagnosed with steatosis hepatis (I°: 63.6%, II°/III°: 36.4%). Children with steatosis hepatis had significantly lower z-scores of circulating leptin levels compared to children with an unremarkable liver ultrasonography (-2.1 ± 0.8 vs. -0.7 ± 0.6). Z-scores of circulating leptin levels correlate negatively with degree of steatosis hepatis. Children with low z-scores of circulating leptin levels had significantly higher triglyceride, fasting insulin and c-peptide levels compared to children with normal z-scores of circulating leptin levels., Conclusion: Prepubertal children with NAFLD and obesity and partial leptin deficiency might be defined as a clinical subgroup., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brandt, von Schnurbein, Denzer, Kratzer and Wabitsch.)

Competing Interests: Declaration of financial interestsReceipt of research funding: no; receipt of payment/financial advantage for providing services as a lecturer: no; paid consultant/internal trainer/salaried employee: no; patent/business interest/shares (author/partner, spouse, children) in company: no; patent/business interest/shares (author/partner, spouse, children) in sponsor of this CME article or in company whose interests are affected by the CME article: no.Declaration of non-financial interestsThe authors declare that there is no conflict of interest.

The sonographic findings in alveolar echinococcosis (AE) and cystic echinococcosis (CE) are complex and can pose significant differential diagnostic problems. They may present like complicated cysts or malignant tumors in the liver. We will discuss the diagnostic difficulties and pitfalls of these two diseases based on case histories., Competing Interests: Declaration of financial interestsReceipt of research funding: no; receipt of payment/financial advantage for providing services as a lecturer: no; paid consultant/internal trainer/salaried employee: no; patent/business interest/shares (author/partner, spouse, children) in company: no; patent/business interest/shares (author/partner, spouse, children) in sponsor of this CME article or in company whose interests are affected by the CME article: no.Declaration of non-financial interestsThe authors declare that there is no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Purpose: Undesirable drug interactions are frequent, they endanger the success of therapy, and they lead to adverse drug reactions. The present study aimed to evaluate statistically potentially drug interactions in a locally circumscribed, random sample population., Patients and Methods: In a random sample population of 264 patients taking medications, we performed analyses with the drug information system AiDKlinik ® . Statistical analysis was performed using SAS version 9.4., Results: Statistically potentially drug interactions were recorded in 82/264 (31.1%) subjects, including 39/82 (47.56%) men, and 43/82 (52.43%) women ( χ 2 = 0.081; p = 0.776). The average number of potential possible interactions detected per person was 1.60 ± 1.21. The regression model with the variables age, body-mass-index and number of long-term-medications shows a significant association between the number of long-term medications taken and the number of moderately severe and severe reactions to drug interactions (F(3.239) = 28.67, p < 0.0001; (t(239) 8.28; p < 0.0001)). After backward elimination, the regression model showed a significant interaction with the number of long-term medications (t (240) = 8.73, p < 0.0001) and body-mass-index (t (240) = 2.02, p = 0.0442). In descriptive analysis, the highest percentages of potential drug interactions occurred in 42/82 (51.22%) subjects with body mass indices (BMIs) >25 kg/m 2 and in 28/82 (34.15%) subjects aged 61-70 years., Conclusion: Number of long-term medications use, age, and obesity may lead to increased drug-drug interactions in a random population sample., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Schmidberger et al.)

Background: The aim of the study was to compare methods for the assessment of vascularisation of liver metastases (LM) between superb microvascular imaging (SMI), contrast-enhanced ultrasound, and microvascular density (MVD)., Methods: SMI results were quantified as the vascularisation quotient (VQ), based on a grey-scale analysis with ImageJ image software. Those results were compared to contrast-enhanced ultrasonography (CEUS) values, calculated with VueBox ® . MVD was measured with an anti-CD34 antibody., Results: This study included 13 patients with LM. The VQ showed a strong correlation with the quantified parameters of contrast-enhanced ultrasound. The parameters of quantified contrast-enhanced ultrasound compared with quantified SMI showed the following statistical correlations: peak enhancement (PE), in arbitrary unit (a.u.) (r=0.72104, P=0.0054), PE in Decibel (dB) (r=0.65918, P=0.00141), Wash-in- Area Under the Curve (WiAUC) in a.u. (r=0.63604, P=0.00194), Wash-in Perfusion-Index (WiPI) in a.u. (r=0.73337, P=0.0043), Wash-in Perfusion-Index (WiPI) in dB (r=0.65642, P=0.0194), Wash-in-Rate (WiR) in a.u. (r=0.7304, P=0.0036) and Wash-in-Rate (WiR) in dB (r=0.82897, P=0.0005)., Conclusions: Comparison of the two methods, SMI and contrast-enhanced ultrasound (CEUS), for quantitative assessment of vascularisation of LM showed good correlation. The contrast-independent Doppler technique SMI can qualitatively assess the vascularisation of LM., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-383). The authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective:  Alveolar echinococcosis (AE) is a rare disease in Austria, Switzerland and Germany (DACh) caused by an infection with the parasite Echinococcus multilocularis. The aim of the study was to describe differences in the detection and reporting systems of alveolar echinococcosis in Austria, Switzerland and Germany and to describe epidemiological trends., Methodology:  As part of an epidemiological update on 6 th September 2019 in Ulm, Germany, experts and representatives discussed differences in the reporting and recording systems as well as the current epidemiological situation., Results:  Since 2004, Austria has had an obligation to report suspected cases, diseases and deaths of alveolar echinococcosis by name in accordance with §1 Para. 1 of the Epidemiegesetz 1950 (EpidemieG) and the Ordinance on Notifiable Communicable Diseases. According to §7 Para. 3 of the German Infection Protection Act (IfSG), Germany has also been subject to a reporting obligation since 2001, but not by name. In addition, national registers are available in both countries, which can be used to answer scientific questions. In Switzerland, there is no obligation to report human alveolar echinococcosis since 1997. Efforts are currently being made to implement a national register for alveolar echinococcosis in Switzerland. Despite different reporting and recording systems, a similar epidemiological trend can be observed for DACh., Conclusions:  In Austria, Switzerland and Germany there is a slightly increasing trend of human cases with alveolar echinococcosis. The direct comparability is limited due to different reporting obligations. The structures often do not allow a joint answering of scientific questions concerning diagnostics, treatment and care., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenskonflikt besteht., (Thieme. All rights reserved.)

Background: The Doppler sonography technique known as "superb microvascular imaging" (SMI) is advancing sonographic micro vascularization imaging in various disciplines. In this study, we aimed to determine whether SMI could reliably reproduce the blood flow in thyroid nodes and whether malignancy could be diagnosed, based on vascularization properties. Immunhistochemical staining by CD34 and SMI where used to determine the vascularization of nodes in terms of quantified vascularization parameters gained by computational evaluation., Methods: We used image analysis programs to investigate whether the quantitative value for vascularization strength in the thyroid node, measured with SMI, was correlated with the actual degree of vascularization, determined microscopically. We included 16 patients that underwent thyroid resections. We prepared thyroid gland tissue slices for immunohistochemistry and labelled endothelial cells with CD34 to visualize blood vessels microscopically. We used image analysis programs, ImageJ, to quantify SMI Doppler sonographic measurements and CellProfiler to quantify CD34 expression in histological sections. We evaluated the numeric values for diagnostic value in node differentiation. Furthermore, we compared these values to check for correlations., Results: Among the 16 nodes studied, three harboured malignant tumours (18.75%): two papillary and one follicular carcinoma. Among the 13 benign lesions (81.25%), four harboured follicular adenomas. Malignant and benign nodes were not significantly different in sonographic (0.88 ± 0.89 vs. 1.13 ± 0.19; p = 0.2790) or immunohistochemical measurements of vascularization strength (0.05 ± 0.05 vs. 0.08 ± 0.06; p = 0.2260)., Conclusion: We found a positive, significant correlation (r = 0.55588; p = 0.0254) between SMI (quantitative values for vascularization strength) and immunohistochemistry (CD34 staining) evaluations of thyroid nodes., (© 2021. The Author(s).)

Background: When Echinococcus multilocularis infects humans as a false intermediate host, alveolar echinococcosis (AE) usually manifests primarily intrahepatically and is initially asymptomatic. If the disease remains undiagnosed and untreated, progressive growth occurs, reminiscent of malignant tumours. The only curative therapy is complete resection, which is limited to localised stages, and palliative drug therapy is used otherwise. Consequently, early diagnosis and reliable detection of AE lesions are important. For this reason, abdominal ultrasonography, as the most common primary imaging for AE, relies on classification systems., Aim: To investigate how hepatic AE lesion sonomorphology changes over time in the Echinococcosis Multilocularis Ulm Classification (EMUC)-ultrasound (US) classification., Methods: Based on data from Germany's national echinococcosis database, we evaluated clinical and US imaging data for 59 patients according to the AE case definition in our preliminary retrospective longitudinal study. There had to be at least two liver sonographies ≥ 6 mo apart, ≥ 1 hepatic AE lesion, and complete documentation in all US examinations. The minimum interval between two separately evaluated US examinations was 4 wk. The AE reference lesion was the largest hepatic AE lesion at the time of the first US examination. To classify the sonomorphologic pattern, we used EMUC-US. In addition to classifying the findings of the original US examiner, all reference lesions at each examination time point were assigned EMUC-US patterns in a blinded fashion by two investigators experienced in US diagnosis. Statistical analysis was performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, United Stated). P values < 0.05 were considered statistically significant., Results: The preliminary study included 59 patients, 38 (64.5%) women and 21 (35.6%) men. The mean age at initial diagnosis was 59.9 ± 16.9 years. At the time of initial ultrasonography, a hailstorm pattern was present in 42.4% (25/59) of cases, a hemangioma-like pattern in 16.9% (10/59), a pseudocystic pattern in 15.3% (9/59), and a metastasis-like pattern in 25.4% (15/59). For the hailstorm pattern, the average lesion size was 67.4 ± 26.3 mm. The average lesion size was 113.7 ± 40.8 mm with the pseudocystic pattern and 83.5 ± 27.3 mm with the hemangioma-like pattern. An average lesion size of 21.7 ± 11.0 mm was determined for the metastasis-like pattern. Although the sonomorphologic pattern remained unchanged in 84.7% (50/59) of AE reference lesions, 15.3% (9/59) showed a change over time. A change in pattern was seen exclusively for AE lesions initially classified as hemangioma-like or pseudocystic. A total of 70% (7/10) of AE lesions initially classified as hemangioma-like showed a relevant change in pattern over time, and 85.7% (6/7) of these were secondarily classified as having a hailstorm pattern, with the remainder (1/7; 14.3%) classified as having a pseudocystic pattern. A total of 22.2% (2/9) of AE lesions initially classified as pseudocystic showed a relevant change in pattern over time and were classified as having a hailstorm pattern. For AE lesions initially classified as having a hailstorm or metastatic pattern, no pattern change was evident. All patients with pattern change were on continuous drug therapy with albendazole., Conclusion: The sonomorphology of hepatic AE lesions may change over time. The hemangioma-like and pseudocystic patterns are affected., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background:  The state of research in the field of abdominal ultrasonography has been deficient for years at German university hospitals. Neither research activity nor funding are appropriate given the actual clinical importance of this method., Objective:  In analogy to studies conducted in 1999 and 2009, this study aims to provide a survey into the state of research in the field of abdominal ultrasonography at German university hospitals. It focuses on the topics of research activity, research funding, publication rate and the development of structural conditions., Methods:  Chief gastroenterologists from Germany's 34 university hospitals were invited to respond to a postal survey asking about the aforementioned topics. We asked them to forward the survey in case somebody else was responsible for the respective tasks. The response rate was 79 %., Results:  The amount of hospitals doing research has roughly remained the same with 77 % compared to 74 % in 2009 and 80 % in 1999. On average, however, there are less research projects per department with 3.2 at the moment compared to 3.5 in 1999 and 3.6 in 2009, and research funding has continued to worsen. 75 % of the heads of departments state that they have not received any funding in addition to the usual budget. Funding by producers of ultrasound machines has also reached a low with 11 % compared to 45 % in 2009 and 31 % in 1999. Only public and university funding show a positive trend. The Deutsche Forschungsgemeinschaft (German Research Foundation) is currently not funding any research projects in the field of abdominal ultrasonography. 13 university hospitals provided information about their publication rate in 1999, 2009 and 2019. Whereas the rate had generally remained constant in the previous studies, the annual number of publications has continually increased in the current survey period. 75 % of the publications came from university hospitals that have established or are currently planning to establish interdisciplinary ultrasound centers. The previous studies also showed that more and more hospitals publish in English instead of German. This trend continues. During the survey period, 60 % of publications were both in English and German, 37 % in English and only 3 % exclusively in German. Most publications dealt with clinical and only a few technical or basic research questions. This was also the case in the previous studies. There have been less publications on the use of ultrasound contrast agents in the present survey period. There is also a decline in the number of systematic reviews. Similar to 2009, the impact factor of journals devoted to sonography is increasing and it is growing stronger than that of journals dedicated to radiology. However, only 29 % of the heads of departments agreed that ultrasonography was a field of research that improves your career prospects., Conclusions:  The present study did not show a significant improvement of research activity in the field of abdominal ultrasonography. However, an increased publication rate indicates a trend towards high-performing research centers. Research funding remains deficient and has worsened in the past 20 years. The demands made by the previous studies for research funding appropriate to the importance of this clinical method remain., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background:  We aimed to determine the prevalence and incidence of gallbladder stones in a random population-based collective in Germany., Methods:  We determined the prevalence and incidence rates of gallbladder stones in a random population sample of 1909 individuals from the Echinococcus-multilocularis in Leutkirch (EMIL) study in 2002 and 380 individuals in a follow-up analysis in the year 2013. The sonographic analysis was performed with a Philipps HDI 5000 (2002) and IU 22 (2013) (Netherlands) transducer 1-5 MHz. Statistical analysis was performed using SAS Version 9.4., Results:  The prevalence of gallbladder stones was 3.8 % (69/1909) in 2002 and 10.8 % (41/380) in 2013. In 2013, the gallbladder stone prevalence was 15.1 % (26/172) in women, compared to 7.2 % (15/208) in men. No gallbladder stones were found in participants in the 18-30 or 31-40 age groups. The average annual incidence was 1.03 % in the 41-50 age group, 0.79 % in the 51-65 age group, and 0.63 % in the > 65 age group. The annual incidence was higher among women (1.04 %) than men (0.53 %). The age-associated annual incidence rates for women and men were 1.93 % and 0.5 % in the 41-50 age group, 0.8 % and 0.78 % in the 51-65 age group, and 1.06 % and 0.30 % in the > 65 age group., Conclusion:  For the investigated German collective from 2002 to 2013, the average annual incidence of gallbladder stones was 0.75 %, with a higher incidence rate among women. These results are consistent with data from comparable international studies., Competing Interests: The Ethics Committee of the Baden-Württemberg Medical Association approved the EMIL-I study in 2002 and the EMIL-II study in 2013 (Application numbers 133/02 and 244/13, respectively). The participating patients gave their written consent., (Thieme. All rights reserved.)

Background: The main endemic areas of alveolar echinococcosis (AE) are in central Europe and western China. The infiltration of intrahepatic vascular and bile ducts as well as extrahepatic disease can lead to complications and may increase morbidity in AE., Purpose: To evaluate the vascular/biliary involvement of hepatic alveolar echinococcosis (HAE) and distant extrahepatic disease at each of four locations in Germany, France, and China., Material and Methods: Contrast-enhanced abdominal magnetic resonance imaging (MRI) scans of patients with HAE, 200 in total, were evaluated by five examiners. AE liver lesions were classified according to Kodama's classification. Furthermore, distant extrahepatic manifestations were documented with additionally performed imaging modalities. Vascular/biliary involvement of hepatic manifestations as well as the presence of extrahepatic manifestations were correlated with the respective Kodama type of the liver lesion., Results: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (12/100 vs. 3/100; Fisher's exact test: P =0.0286). A significant relationship exists between presence of distant extrahepatic disease manifestation and size of the AE liver lesion (132.53 ± 48.65 vs. 92.49 ± 50.06; P  = 0.0030). Vascular/biliary involvement is significantly more frequent in China than in Europe (86/100 vs. 65/100; χ 2  = 11.92; P  = 0.0006). Vascular/biliary involvement depends on lesion size (111.10 ± 47.44 vs. 47.36 ± 24.36; P <0.0001). Different types of AE liver lesions are associated with differences in vascular/biliary involvement and extrahepatic manifestations., Conclusion: Vascular/biliary involvement and presence of distant extrahepatic manifestations depend on size of the HAE lesions and are more frequently detected in China. Different MRI morphological patterns influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations.

Background: Few systematic comparative studies of the different methods of physical elastography of the spleen are currently available., Aim: To compare point shear wave and two-dimensional elastography of the spleen considering the anatomical location (upper, hilar, and lower pole)., Methods: As part of a prospective clinical study, healthy volunteers were examined for splenic elasticity using four different ultrasound devices between May 2015 and April 2017. The devices used for point shear wave elastography were from Siemens (S 3000) and Philips (Epiq 7), and those used for two-dimensional shear wave elastography were from GE (Logiq E9) and Toshiba (Aplio 500). In addition, two different software versions (5.0 and 6.0) were evaluated for the Toshiba ultrasound device (Aplio 500). The study consisted of three arms: A, B, and C., Results: In study arm A, 200 subjects were evaluated (78 males and 122 females, mean age 27.9 ± 8.1 years). In study arm B, 113 subjects were evaluated (38 men and 75 women, mean age 26.0 ± 6.3 years). In study arm C, 44 subjects were enrolled. A significant correlation of the shear wave velocities at the upper third of the spleen ( r = 0.33088, P < 0.0001) was demonstrated only for the Philips Epiq 7 device compared to the Siemens Acuson S 3000. In comparisons of the other ultrasound devices (GE, Siemens, Toshiba), no comparable results could be obtained for any anatomical position of the spleen. The influencing factors age, gender, and body mass index did not show a clear correlation with the measured shear wave velocities., Conclusion: The absolute values of the shear wave elastography measurements of the spleen and the two different elastography methods are not comparable between different manufacturers or models., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives:  This study aimed to compare spleen sizes in a hospital and a population sample using ultrasound and define normal values and factors influencing spleen size., Methods:  Both samples' spleen sizes (n = 1520) were measured using ultrasound under the same conditions. Blood counts and other laboratory parameters were determined under the same conditions in both samples., Results:  In the hospital sample (n = 760), the mean spleen size was 114.7 mm, and in the population sample (n = 760), it was 99.1 mm. In both, spleen size in men was significantly higher than in women (p < 0.0001) and influenced by body height, weight, and BMI (body mass index) (p < 0.0001). In the hospital sample, there was a correlation with higher values for ALT (p = 0.0160), AST (p = 0.0394), AP (p = 0.0482), and ferritin (p = 0.0008) and lower values for HDL (p = 0.0091) and thrombocytes (p < 0.0001). In the multivariate analysis, higher values for AP (p = 0.0059) and lower values for hemoglobin (p = 0.0014) and thrombocytes (p = 0.0001) were found. Stratified for sex (men, women), spleen size increased with higher values for ALT (p = 0.0116, p = 0.0113), AST (p = 0.0014, p = 0.0113), and AP (p = 0.0001, p = 0.0012), and with lower values of hemoglobin (p = 0.0057, p = 0.0016), thrombocytes (p < 0.0001, p = 0.0003), and albumin (p = 0.0029, p = 0.0432). In women, there was a discordant correlation with red blood cells (p = 0.0005) and a concordant correlation with GGT (p = 0.0241), and in men discordant correlations with cholesterol (p = 0.0010) and HDL (p = 0.0404)., Conclusions:  The already proven impact of anthropometric data on spleen size was confirmed. The role of laboratory values should be further analyzed., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background:  This prospective multicenter study funded by the DEGUM assesses the diagnostic accuracy of standardized contrast-enhanced ultrasound (CEUS) for the noninvasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients., Methods:  Patients at high risk for HCC with a histologically proven focal liver lesion on B-mode ultrasound were recruited prospectively in a multicenter approach. Clinical and imaging data were entered via online entry forms. The diagnostic accuracies for the noninvasive diagnosis of HCC were compared for the conventional interpretation of standardized CEUS at the time of the examination (= CEUS on-site) and the two CEUS algorithms ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) and CEUS LI-RADS (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System)., Results:  321 patients were recruited in 43 centers; 299 (93.1 %) had liver cirrhosis. The diagnosis according to histology was HCC in 256 cases, and intrahepatic cholangiocarcinoma (iCCA) in 23 cases. In the subgroup of cirrhotic patients (n = 299), the highest sensitivity for the diagnosis of HCC was achieved with the CEUS algorithm ESCULAP (94.2 %) and CEUS on-site (90.9 %). The lowest sensitivity was reached with the CEUS LI-RADS algorithm (64 %; p < 0.001). However, the specificity of CEUS LI-RADS (78.9 %) was superior to that of ESCULAP (50.9 %) and CEUS on-site (64.9 %; p < 0.001). At the same time, the negative predictive value (NPV) of CEUS LI-RADS was significantly inferior to that of ESCULAP (34.1 % vs. 67.4 %; p < 0.001) and CEUS on-site (62.7 %; p < 0.001). The positive predictive values of all modalities were high (around 90 %), with the best results seen for CEUS LI-RADS and CEUS on-site., Conclusion:  This is the first multicenter, prospective comparison of standardized CEUS and the recently developed CEUS-based algorithms in histologically proven liver lesions in cirrhotic patients. Our results reaffirm the excellent diagnostic accuracy of CEUS for the noninvasive diagnosis of HCC in high-risk patients. However, on-site diagnosis by an experienced examiner achieves an almost equal diagnostic accuracy compared to CEUS-based diagnostic algorithms., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: Determining the normal values for acoustic radiation force impulse (ARFI) shear wave elastography of the thoracolumbar fascia (TLF) and define possible factors of influence., Methods: We measured the shear wave velocity (SWV) in m/s and the diameter (anterior-posterior) in mm of the TLF bilateral in 267 healthy participants with the Acuson S3000™ (Siemens) using the virtual touch image quantification mode (VTIQ). The parameters were tested for correlations with the anthropometric data of the participants, between different age groups and the genders, as well as information obtained from the history, such as smoking and sporting activities., Results: We determined a mean SWV of 3.28 ± 0.55 m/s for the left thoracolumbar fascia and 3.44 ± 0.55 m/s for the right. The diameter on the right was 2.7 ± 0.8 mm. On the left, it was 2.7 ± 0.9 mm. Neither body mass index (BMI) nor gender had a significant effect on either of the measured parameters (p > 0.05). The same goes for regular medication, sporting activity or the consumption of alcohol (p > 0.05). The results concerning the effect of smoking and age were inconclusive as they only had a significant influence to either the right or the left side of the TLF but not on the other side., Conclusions: We collected the normal value for ARFI shear wave elastography of the TLF in 267 healthy participants. Furthermore, neither gender, BMI, sports activity nor the consumption of alcohol affected the elasticity or the diameter of the thoracolumbar fascia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective:  In Germany, there is no standardized ultrasound training. This study aims to provide a survey into the current state of abdominal ultrasonography training at German university hospitals as well as a comparative analysis of the results from studies conducted in 1999 and 2009., Methods:  Chief gastroenterologists from Germany's 34 university hospitals were invited to respond to a postal survey asking about technical equipment, the number of ultrasound scans, the role of professional societies and undergraduate as well as postgraduate training. The response rate was 79 %. In addition, 1183 medical students from 34 faculties completed a complementary online teaching evaluation., Results:  At university hospitals, abdominal ultrasonography is conducted in an increasingly interdisciplinary context. Today, 29 % of university hospitals have interdisciplinary ultrasound centers. The study shows that the number of available ultrasound machines has increased - each hospital has an average of 5.2 systems. This is an increase of 30 % in comparison to 2009 and of 27 % in comparison to 1999. However, the willingness to invest in modern ultrasound machines has decreased. The total number of ultrasound scans as well as the number of contrast-enhanced ultrasound scans have steadily increased over the past years - with a maximum increase of 28 % between 2009 and 2018. The German Society of Ultrasound in Medicine (DEGUM) is increasingly present at university hospitals. It has further strengthened its prominent role in quality assurance and specialist training. Today, 96 % of the chief gastroenterologists are members of DEGUM and 89 % have obtained further qualification offered by the society. Concerning the duration of the training, the number of mandatory examinations and the amount of supervision, there are still considerable differences among the departments. On average, more doctors are trained per department and year. A 6-month full-time training has been established at most hospitals. Sonography enjoys a high standing among students and the findings show a strong readiness for work in that field. The number of practical courses and students has been increasing over the past years. However, there is often an imbalance between the number of courses offered and students who want to enroll., Conclusions:  Training conditions have improved for medical staff as well as students despite the fact that there are still considerable differences in quality among the hospitals. The number of ultrasound scans is steadily increasing in all departments. The study did not show any adequate improvement in the availability of technical equipment. The German Society of Ultrasound in Medicine (DEGUM) has further strengthened its leading position in the field of sonography., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background:  Ultrasound as a non-ionizing imaging procedure is one of the most important diagnostic procedures in everyday clinical practice. The technology is widely used. Due to constant technical innovations, sonographic procedures, such as contrast-enhanced ultrasound (CEUS), sonoelastography, new microvascular Doppler modalities and, as an example of interventional procedures, sonographically controlled microwave ablation (MWA), are becoming increasingly important in diagnostic imaging and interventional medicine alongside CT and MRI. However, this also requires greater expertise, specialization and qualification on the part of users., Method:  This review article provides information about the range of technical innovations in ultrasound in recent years and describes the underlying technology, the clinical applications, and their diagnostic value. These are presented in the context of the current literature, explaining their advantages and disadvantages and their clinical value., Results and Conclusion:  Contrast-enhanced ultrasound (CEUS), microvascular Doppler modalities, fusion imaging and elastography complement B-scan ultrasound and conventional Doppler procedures for various problems. Microwave ablation (MWA) has a firm place as an ablative procedure for local tumor therapy in different organ systems and can be performed under ultrasound guidance. Thanks to new developments, the possibilities of ultrasound are now greater than ever. Knowledge of the technology, indications, and possible applications of newer procedures is essential for adequate patient care., Key Points:   · Contrast-enhanced ultrasound (CEUS) allows an increase in sensitivity and specificity in the assessment of parenchymal lesions.. · CEUS allows the microperfusion to be visualized and quantified. For larger vessels, CEUS is an important instrument in diagnosing endoleak after stenting.. · Microvascular Doppler techniques with clutter suppression algorithms allow a more accurate representation of the smallest vessels than regular color or power Doppler.. · Elastography of the liver in diffuse hepatopathies is a noninvasive diagnostic tool to exclude higher grade fibrosis/cirrhosis.. · Microwave ablation (MWA) also offers sonographically controlled ablation of tumors.., Citation Format: · Kloth C, Kratzer W, Schmidberger J et al. Ultrasound 2020 - Diagnostics & Therapy: On the Way to Multimodal Ultrasound: Contrast-Enhanced Ultrasound (CEUS), Microvascular Doppler Techniques, Fusion Imaging, Sonoelastography, Interventional Sonography . Fortschr Röntgenstr 2021; 193: 23 - 32., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Alveolar (AE) and cystic echinococcosis (CE) in humans are caused by the metacestode of the tapeworms Echinococcus multilocularis and Echinococcus granulosus sensu lato (s.l.). Immunohistochemistry with the monoclonal antibodies (mAb) Em2G11, specific for AE, and the mAb EmG3, specific for AE and CE, is an important pillar of the histological diagnosis of these two infections. Our aim was to further evaluate mAb EmG3 in a diagnostic setting and to analyze in detail the localization, distribution, and impact of small particles of Echinococcus multilocularis (spems) and small particles of Echinococcus granulosus s.l. (spegs) on lymph nodes., Methodology/principal Findings: We evaluated the mAb EmG3 in a cohort of formalin-fixed, paraffin embedded (FFPE) specimens of AE (n = 360) and CE (n = 178). These samples originated from 156 AE-patients and 77 CE-patients. mAb EmG3 showed a specific staining of the metacestode stadium of E. multilocularis and E. granulosus s.l. and had a higher sensitivity for spems than mAb Em2G11. Furthermore, we detected spegs in the surrounding host tissue and in almost all tested lymph nodes (39/41) of infected patients. 38/47 lymph nodes of AE showed a positive reaction for spems with mAb EmG3, whereas 29/47 tested positive when stained with mAb Em2G11. Spegs were detected in the germinal centers, co-located with CD23-positive follicular dendritic cells, and were present in the sinuses. Likewise, lymph nodes with spems and spegs in AE and CE were significantly enlarged in size in comparison to the control group., Conclusions/significance: mAb EmG3 is specific for AE and CE and is a valuable tool in the histological diagnosis of echinococcosis. Based on the observed staining patterns, we hypothesize that the interaction between parasite and host is not restricted to the main lesion since spegs are detected in lymph nodes. Moreover, in AE the number of spems-affected lymph nodes is higher than previously assumed. The enlargement of lymph nodes with spems and spegs points to an immunological interaction with the small immunogenic particles (spems and spegs) of Echinococcus spp., Competing Interests: The authors have declared that no competing interests exist.

Alveolar echinococcosis (AE) is a rare zoonotic disease caused by the larval stage of Echinococcus multilocularis. Despite its low world-wide prevalence, this disease shows differences in the regional distribution of cases. In the present cohort study, we analyse the distribution of AE according to environmental and geographical factors in Germany. We identified the place of residence of 591 cases of AE from the national database for AE, and georeferenced these localities in the Universal Transverse Mercator coordinate system. Data on elevation, air temperature, precipitation height and land cover were mapped out and correlated with the distribution of cases of disease during the period 1992-2018. Moran's I statistic was used for spatial autocorrelation. Differences in frequency distribution between elevation, air temperature, precipitation height and landscape feature classes were analysed with the Kruskal-Wallis test. With the multiple linear regression analysis, we determined the influences and interactions of geographical and climatic factors on the number of AE cases. The results showed a heterogeneous distribution of AE cases with a higher concentration in southern Germany than in the rest of Germany (I = 0.225517, Z = 35.8182 and p < 0.001). There was a statistically significant difference in frequency distribution between precipitation height, air temperature, elevation and landscape feature classes and AE cases in Germany (p < 0.0001). In regions with higher elevations (505-672 m), moderate average air temperatures (6.0-7.9°C) and higher precipitation rates (701-1000 mm) most AE cases were recorded. It seems, that regions with higher precipitation rates, higher elevations and moderate average air temperatures have a higher infection burden and infection conditions. It is therefore extremely important to generate greater awareness of the disease in these regions, with the aim of recognising potential cases of AE as early as possible and introducing the appropriate therapeutic measures., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The main endemic areas of alveolar echinococcosis (AE) are in Central Europe and Western China. Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE., Aim: To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim., Methods: Consecutively, five experienced examiners evaluated contrast-enhanced abdominal computed tomography (CT) scans for 200 patients with hepatic AE of each of four locations ( n = 50) in Germany, France and China. Therefore, we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center, performed because of hepatic AE from September 21, 2007 to March 21, 2018. AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT (EMUC-CT). Distant extrahepatic manifestations were documented either by whole body positron emission tomography-CT or with the addition of thoracic CT and cranial magnetic resonance imaging. Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion. Statistical analysis was performed using SAS Version 9.4 (SAS Institute Inc., Cary, NC, United States)., Results: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe ( P = 0.0091). A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size ( P = 0.0075). Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe ( P < 0.0001), and vascular/biliary involvement depended on lesion size. Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations: Vascular/biliary involvement as a function of lesions primary morphology ranged from 5.88% of type IV liver lesions to 100% among type III lesions. Type IV differed significantly in these associations from types I, II, and III ( P < 0.0001). With respect to extrahepatic disease, the primary morphology types IV and V of liver lesions were not associated with any case of distant extrahepatic disease. In contrast, distant extrahepatic manifestations in types I-III were found to varying degrees, with a maximum of 22% for type III., Conclusion: Different CT morphological patterns of hepatic AE lesions influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations. There are intercontinental differences regarding the characteristics of AE manifestation., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Alveolar echinococcosis (AE) is caused by the intermediate stage of Echinococcus multilocularis . We aimed to correlate computed tomography (CT) data with histology to identify distinct characteristics for different lesion types. We classified 45 samples into five types with the Echinococcus multilocularis Ulm Classification for Computed Tomography (EMUC-CT). The various CT lesions exhibited significantly different histological parameters, which led us to propose a progression model. The initial lesion fit the CT type IV classification, which comprises a single necrotic area with the central located laminated layer, a larger distance between laminated layer and border zone, a small fibrotic peripheral zone, and few small particles of Echinococcus multilocularis (spems). Lesions could progress through CT types I, II, and III, characterized by shorter distances between laminated layer and border zone, more spems inside and surrounding the lesion, and a pronounced fibrotic rim (mostly in type III). Alternatively, lesions could converge to a highly calcified, regressive state (type V). Our results suggest that the CT types mark sequential stages of the infection, which progress over time. These distinct histological patterns advance the understanding of interactions between AE and human host; moreover, they might become prognostically and therapeutically relevant.

Positron emission tomography-computed tomography (PET-CT) with 18F-fluorodesoxyglucose (FDG) is the imaging modality of choice for assessing inflammation surrounding hepatic alveolar echinococcosis (AE) lesions. This study is the first to evaluate FDG uptake in hepatic AE (n = 51) based on the standardized uptake value (SUV) and to correlate the SUVs with primary morphology and calcification patterns, based on the Echinococcus multilocularis Ulm Classification for Computed-Tomography (EMUC-CT). Our results show that the SUVs were increased for lesions with EMUC-CT types I-IV primary morphology, compared to the surrounding healthy liver tissue (SUV = 2.5 ± 0.4; p < 0.05). Type IV lesions included, by far, the highest number of PET-negative lesions. A comparison of lesions with different primary morphologies showed clear differences. The highest SUVs were found for types I and III, and the lowest was found for type IV. Type IV lesions (SUV, 3.8 ± 1.5) showed significantly lower uptake compared to type I (SUV, 6.9 ± 3.5; p = 0.030) and type III (SUV, 7.4 ± 3.9; p = 0.031) lesions. For type II lesions, the results showed only a statistical trend (SUV, 6.1 ± 3.1; p = 0.073). Due to the small number of cases, an evaluation of type V (n = 1) lesions was not possible. The different SUVs of lesions with different primary morphologies, particularly the lower FDG uptake observed in type IV lesions, suggested that these SUVs might reflect different stages of the disease.