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Inflammatory bowel diseases are medically intractable and require constant therapy in many cases. While a growing number of biologicals and small molecules is available for treatment, a substantial portion of patients experiences primary non-response to these compounds and head-to-head evidence for therapy selection is scarce. Thus, approaches to predict treatment success in individual patients are a huge unmet need. We had previously suggested that the expression and function of α4β7 integrin on T cells in the peripheral blood correlate to outcomes of therapy with the anti-α4β7 integrin antibody vedolizumab. Here, we conducted a translational multicenter trial to prospectively evaluate this hypothesis. In a cohort of 89 patients with inflammatory bowel disease undergoing regular therapy with vedolizumab, lower baseline expression of α4β7 was associated with short-term clinical response. Consistently, low α4β7 expression in patients achieving remission predicted sustained remission in week 30. Moreover, high dynamic adhesion of CD4

BackgroundFibrostenotic disease is a common complication in Crohn’s disease (CD) patients hallmarked by transmural extracellular matrix (ECM) accumulation in the intestinal wall. The prevention and medical therapy of fibrostenotic CD is an unmet high clinical need. Although targeting IL36R signaling is a promising therapy option, downstream mediators of IL36 during inflammation and fibrosis have been incompletely understood. Candidate molecules include matrix metalloproteinases which mediate ECM turnover and are thereby potential targets for anti-fibrotic treatment. Here, we have focused on understanding the role of MMP13 during intestinal fibrosis.MethodsWe performed bulk RNA sequencing of paired colon biopsies taken from non-stenotic and stenotic areas of patients with CD. Corresponding tissue samples from healthy controls and CD patients with stenosis were used for immunofluorescent (IF) staining. MMP13 gene expression was analyzed in cDNA of intestinal biopsies from healthy controls and in subpopulations of patients with CD in the IBDome cohort. In addition, gene regulation on RNA and protein level was studied in colon tissue and primary intestinal fibroblasts from mice upon IL36R activation or blockade. Finally, in vivo studies were performed with MMP13 deficient mice and littermate controls in an experimental model of intestinal fibrosis. Ex vivo tissue analysis included Masson’s Trichrome and Sirius Red staining as well as evaluation of immune cells, fibroblasts and collagen VI by IF analysis.ResultsBulk RNA sequencing revealed high upregulation of MMP13 in colon biopsies from stenotic areas, as compared to non-stenotic regions of patients with CD. IF analysis confirmed higher levels of MMP13 in stenotic tissue sections of CD patients and demonstrated αSMA+ and Pdpn+ fibroblasts as a major source. Mechanistic experiments demonstrated that MMP13 expression was regulated by IL36R signaling. Finally, MMP13 deficient mice, as compared to littermate controls, developed less fibrosis in the chronic DSS model and showed reduced numbers of αSMA+ fibroblasts. These findings are consistent with a model suggesting a molecular axis involving IL36R activation in gut resident fibroblasts and MMP13 expression during the pathogenesis of intestinal fibrosis.ConclusionTargeting IL36R-inducible MMP13 could evolve as a promising approach to interfere with the development and progression of intestinal fibrosis.

High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness (CRF) and health-related outcomes in various chronic diseases, including cancer. However, data on feasibility and efficacy of HIIT in advanced cancer patients are still sparse, presumably because of safety concerns, like suspected immunosuppression after vigorous exercise. This randomized, sham-intervention controlled study aimed to investigate feasibility, safety, and preliminary efficacy of very low-volume HIIT (LOW-HIIT) in advanced cancer patients.Twenty-seven patients (55.4 ± 13.2 yr) with different advanced cancers (Union for International Cancer Control [UICC] III/IV) were randomly allocated to LOW-HIIT ( n = 13), consisting of 5 × 1 min cycle ergometer intervals (14 min per session total duration) at 80% to 95% HR peak (two sessions per week for 12 wk), or a sham intervention ( n = 14) performing light physical mobilization exercises (SHAM). Primary outcomes were attrition and attendance rates, with values of ≤25% and ≥80%, respectively, considered acceptable. Secondary outcomes were safety, protocol fidelity, physiological (including CRF measures) and patient-reported outcomes (including fatigue and quality of life).One of 13 patients (8%) receiving LOW-HIIT dropped out. Mean attendance rate was ~93%. The prescribed minimum exercise intensity was consistently reached by all patients. Low-volume HIIT was well tolerated and not associated with any serious adverse event nor with increased infection susceptibility. There were no biochemical signs of acute immunosuppression after LOW-HIIT. Contrarily, differentiation and degranulation of natural killer cells was acutely increased postexercise. Low-volume HIIT improved CRF measures including peak oxygen uptake, self-reported fatigue, physical, and social functioning. No significant changes occurred in the SHAM group.Low-volume HIIT can be regarded as feasible and safe in advanced cancer patients. Our preliminary data indicate favorable acute effects on NK-cells and beneficial chronic adaptations in CRF, fatigue, and aspects of quality of life.

Background and Aims Colorectal cancer [CRC] is one of the most frequent malignancies, but the molecular mechanisms driving cancer growth are incompletely understood. We characterised the roles of the cytokine IL-9 and Th9 cells in regulating CRC development. Methods CRC patient samples and samples from AOM/DSS treated mice were analysed for expression of IL-9, CD3, and PU.1 by FACS analysis and immunohistochemistry. IL-9 citrine reporter mice, IL-9 knockout mice, and PU.1 and GATA3 CD4-Cre conditional knockout mice were studied in the AOM/DSS model. DNA minicircles or hyper-IL-6 were used for overexpression of cytokines in vivo. Effects of IL-6 and IL-9 were determined in organoid and T cell cultures. Claudin2/3 expression was studied by western blotting and bacterial translocation by FISH. Results We uncovered a significant expansion of IL-9- and PU.1-expressing mucosal Th9 cells in CRC patients, with particularly high levels in patients with colitis-associated neoplasias. PU.1+ Th9 cells accumulated in experimental colorectal neoplasias. Deficiency of IL-9 or inactivation of PU.1 in T cells led to impaired tumour growth in vivo, suggesting a protumoral role of Th9 cells. In contrast, GATA3 inactivation did not affect Th9-mediated tumour growth. Mechanistically, IL-9 controls claudin2/3 expression and T cell-derived IL-6 production in colorectal tumours. IL-6 abrogated the anti-proliferative effects of IL-9 in epithelial organoids in vivo. IL-9-producing Th9 cells expand in CRC and control IL-6 production by T cells. Conclusions IL-9 is a crucial regulator of tumour growth in colitis-associated neoplasias and emerges as potential target for therapy.

Increasing insights into the immunopathogenesis of inflammatory bowel diseases [IBD] have led to the advent of targeted therapies that inhibit crucial mediators of the inflammatory process, thereby widening our available therapeutic armamentarium. Anti-tumour necrosis factor [anti-TNF] agents are still a mainstay of our therapeutic endeavours and the introduction of corresponding biosimilars has further widened their use. Nevertheless, only a subgroup of treated patients benefit from the initiated treatment and there is secondary non-response in the course of therapy. Initiation of subsequent therapy often poses a challenge to the treating physician, as non-response to primary anti-TNF treatment generally characterizes a patient group that is more treatment-resistant, which may be due to the immunological impregnation by prior anti-TNF exposure. At present, there is currently no guidance for the most appropriate second-line therapy after anti-TNF failure. Here, we review the efficacy of secondary biological therapy in anti-TNF-treated patients. We focus on and assess available clinical trial data of the emerging substance class of IL-23p19 inhibitors, which have demonstrated remarkable efficacy not only in anti-TNF-naïve but also refractory patients. We present molecular mechanisms that drive IL-23-mediated resistance to ongoing anti-TNF therapy and discuss the dynamic fluidity of the mucosal cytokine network in the course of therapy that perpetuates the mucosal inflammatory reaction. Translation of these findings into clinical practice might finally lead to initiation of the most appropriate therapy at the right time of the individual disease course, which would have important implications for the patient’s probability of response to treatment.

During surgery, rapid and accurate histopathological diagnosis is essential for clinical decision making. Yet the prevalent method of intra-operative consultation pathology is intensive in time, labour and costs, and requires the expertise of trained pathologists. Here we show that biopsy samples can be analysed within 30 min by sequentially assessing the physical phenotypes of singularized suspended cells dissociated from the tissues. The diagnostic method combines the enzyme-free mechanical dissociation of tissues, real-time deformability cytometry at rates of 100–1,000 cells s−1 and data analysis by unsupervised dimensionality reduction and logistic regression. Physical phenotype parameters extracted from brightfield images of single cells distinguished cell subpopulations in various tissues, enhancing or even substituting measurements of molecular markers. We used the method to quantify the degree of colon inflammation and to accurately discriminate healthy and tumorous tissue in biopsy samples of mouse and human colons. This fast and label-free approach may aid the intra-operative detection of pathological changes in solid biopsies.

Focal liver lesions are detected in about 15% of abdominal ultrasound examinations. The diagnosis of frequent benign lesions can be determined reliably based on the characteristic B-mode appearance of cysts, hemangiomas, or typical focal fatty changes. In the case of focal liver lesions which remain unclear on B-mode ultrasound, contrast-enhanced ultrasound (CEUS) increases diagnostic accuracy for the distinction between benign and malignant liver lesions. Artificial intelligence describes applications that try to emulate human intelligence, at least in subfields such as the classification of images. Since ultrasound is considered to be a particularly examiner-dependent technique, the application of artificial intelligence could be an interesting approach for an objective and accurate diagnosis. In this systematic review we analyzed how artificial intelligence can be used to classify the benign or malignant nature and entity of focal liver lesions on the basis of B-mode or CEUS data. In a structured search on Scopus, Web of Science, PubMed, and IEEE, we found 52 studies that met the inclusion criteria. Studies showed good diagnostic performance for both the classification as benign or malignant and the differentiation of individual tumor entities. The results could be improved by inclusion of clinical parameters and were comparable to those of experienced investigators in terms of diagnostic accuracy. However, due to the limited spectrum of lesions included in the studies and a lack of independent validation cohorts, the transfer of the results into clinical practice is limited.

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Supplementary Figures 1-6 from A Key Regulatory Role of the Transcription Factor NFATc2 in Bronchial Adenocarcinoma via CD8+ T Lymphocytes

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The Ca2+-regulated calcineurin/nuclear factor of activated T cells (NFAT) cascade controls alternative pathways of T-cell activation and peripheral tolerance. Here, we describe reduction of NFATc2 mRNA expression in the lungs of patients with bronchial adenocarcinoma. In a murine model of bronchoalveolar adenocarcinoma, mice lacking NFATc2 developed more and larger solid tumors than wild-type littermates. The extent of central tumor necrosis was decreased in the tumors in NFATc2(−/−) mice, and this finding was associated with reduced tumor necrosis factor-α and interleukin-2 (IL-2) production by CD8+ T cells. Adoptive transfer of CD8+ T cells of NFATc2(−/−) mice induced transforming growth factor-β1 in the airways of recipient mice, thus supporting CD4+CD25+Foxp-3+glucocorticoid-induced tumor necrosis factor receptor (GITR)+ regulatory T (Treg) cell survival. Finally, engagement of GITR in NFATc2(−/−) mice induced IFN-γ levels in the airways, reversed the suppression by Treg cells, and costimulated effector CD4+CD25+ (IL-2Rα) and memory CD4+CD127+ (IL-7Rα) T cells, resulting in abrogation of carcinoma progression. Agonistic signaling through GITR, in the absence of NFATc2, thus emerges as a novel possible strategy for the treatment of human bronchial adenocarcinoma in the absence of NFATc2 by enhancing IL-2Rα+ effector and IL-7Rα+ memory-expressing T cells. [Cancer Res 2009;69(7):3069–76]

PDF file - 559K, expression of IL-11 and IL-22

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Supplementary Figure Legends 1-6 from A Key Regulatory Role of the Transcription Factor NFATc2 in Bronchial Adenocarcinoma via CD8+ T Lymphocytes

Patients with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer due to chronic inflammation. In IBD, chronic inflammation relies upon a TGFβ signaling blockade, but its precise mechanistic relationship to colitis-associated colorectal cancer (CAC) remains unclear. In this study, we investigated the role of the TGFβ signaling inhibitor Smad7 in CAC pathogenesis. In human colonic specimens, Smad7 was downregulated in CD4+ T cells located in the lamina propria of patients with complicated IBD compared with uncomplicated IBD. Therefore, we assessed CAC susceptibility in a transgenic mouse model where Smad7 was overexpressed specifically in T cells. In this model, Smad7 overexpression increased colitis severity, but the mice nevertheless developed fewer tumors than nontransgenic mice. Protection was associated with increased expression of IFNγ and increased accumulation of cytotoxic CD8+ and natural killer T cells in the tumors and peritumoral areas. Moreover, genetic deficiency in IFNγ abolished the Smad7-dependent protection against CAC. Taken together, our findings defined a novel and unexpected role for Smad7 in promoting a heightened inflammatory response that protects against CAC. Cancer Res; 71(24); 7423–32. ©2011 AACR.

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ObjectiveIncreased apoptotic shedding has been linked to intestinal barrier dysfunction and development of inflammatory bowel diseases (IBD). In contrast, physiological cell shedding allows the renewal of the epithelial monolayer without compromising the barrier function. Here, we investigated the role of live cell extrusion in epithelial barrier alterations in IBD.DesignTaking advantage of conditional GGTase and RAC1 knockout mice in intestinal epithelial cells (Pggt1biΔIECandRac1iΔIECmice), intravital microscopy, immunostaining, mechanobiology, organoid techniques and RNA sequencing, we analysed cell shedding alterations within the intestinal epithelium. Moreover, we examined human gut tissue and intestinal organoids from patients with IBD for cell shedding alterations and RAC1 function.ResultsEpithelialPggt1bdeletion led to cytoskeleton rearrangement and tight junction redistribution, causing cell overcrowding due to arresting of cell shedding that finally resulted in epithelial leakage and spontaneous mucosal inflammation in the small and to a lesser extent in the large intestine. Both in vivo and in vitro studies (knockout mice, organoids) identified RAC1 as a GGTase target critically involved in prenylation-dependent cytoskeleton dynamics, cell mechanics and epithelial cell shedding. Moreover, inflamed areas of gut tissue from patients with IBD exhibited funnel-like structures, signs of arrested cell shedding and impaired RAC1 function. RAC1 inhibition in human intestinal organoids caused actin alterations compatible with arresting of cell shedding.ConclusionImpaired epithelial RAC1 function causes cell overcrowding and epithelial leakage thus inducing chronic intestinal inflammation. Epithelial RAC1 emerges as key regulator of cytoskeletal dynamics, cell mechanics and intestinal cell shedding. Modulation of RAC1 might be exploited for restoration of epithelial integrity in the gut of patients with IBD.

Intestinal homeostasis and the maintenance of the intestinal epithelial barrier are essential components of host defense during gastrointestinal Salmonella Typhimurium infection. Both require a strict regulation of cell death. However, the molecular pathways regulating epithelial cell death have not been completely understood. Here, we elucidated the contribution of central mechanisms of regulated cell death and upstream regulatory components during gastrointestinal infection. Mice lacking Caspase-8 in the intestinal epithelium are highly sensitive towards bacterial induced enteritis and intestinal inflammation, resulting in an enhanced lethality of these mice. This phenotype was associated with an increased STAT1 activation during Salmonella infection. Cell death, barrier breakdown and systemic infection were abrogated by an additional deletion of STAT1 in Casp8ΔIEC mice. In the absence of epithelial STAT1, loss of epithelial cells was abolished which was accompanied by a reduced Caspase-8 activation. Mechanistically, we demonstrate that epithelial STAT1 acts upstream of Caspase-8-dependent as well as -independent cell death and thus might play a major role at the crossroad of several central cell death pathways in the intestinal epithelium. In summary, we uncovered that transcriptional control of STAT1 is an essential host response mechanism that is required for the maintenance of intestinal barrier function and host survival.

IntroductionMacrophages play an important role in intestinal wound healing. However, the trajectories from circulating monocytes to gut macrophages are incompletely understood.MethodsTaking advantage of mice depleted for non-classical monocytes due to deficiency for the transcription factor Nr4a1, we addressed the relevance of non-classical monocytes for large intestinal wound healing using flow cytometry, in vivo wound healing assays and immunofluorescence.ResultsWe show that wound healing in Nr4a1-deficient mice is substantially delayed and associated with reduced peri-lesional presence of macrophages with a wound healing phenotype.DiscussionOur data suggest that non-classical monocytes are biased towards wound healing macrophages. These insights might help to understand, how targeting monocyte recruitment to the intestine can be used to modulate intestinal macrophage functions.

Targeting cytokines in inflammatory bowel disease (IBD) is a useful clinical approach. Potential therapies for IBD include regulatory T cell transfer to restore cytokine balance, blocking proinflammatory cytokines (e.g., IL-12 and IL-23) or their receptors (sIL-6R and IL-36R), or inhibiting signaling kinases (e.g., JAK). An emerging trend in IBD therapy is to combine several anti-cytokine agents simultaneously.

ObjectiveUlcerative colitis (UC) is a chronic, debilitating immune-mediated disease driven by disturbed mucosal homeostasis, with an excess of intestinal effector T cells and an insufficient expansion of mucosal regulatory T cells (Tregs). We here report on the successful adoptive transfer of autologous, ex vivo expanded Tregs in a patient with refractory UC and associated primary sclerosing cholangitis (PSC), for which effective therapy is currently not available.DesignThe patient received a single infusion of 1×106autologous, ex vivo expanded, polyclonal Tregs per kilogram of body weight, and the clinical, biochemical, endoscopic and histological responses were assessed 4 and 12 weeks after adoptive Treg transfer.ResultsThe patient showed clinical, biochemical, endoscopic and histological signs of response until week 12 after adoptive Treg transfer, which was associated with an enrichment of intestinal CD3+/FoxP3+and CD3+/IL-10+T cells and increased mucosal transforming growth factor beta and amphiregulin levels. Moreover, there was marked improvement of PSC with reduction of liver enzymes. This pronounced effect lasted for 4 weeks before values started to increase again.ConclusionThese findings suggest that adoptive Treg therapy might be effective in refractory UC and might open new avenues for clinical trials in PSC.Trial registration numberNCT04691232.

Background Motorized spiral enteroscopy (MSE) has been shown to be safe and effective for deep enteroscopy in studies performed at expert centers with limited numbers of patients without previous abdominal surgery. This study aimed to investigate the safety, efficacy, and learning curve associated with MSE in a real-life scenario, with the inclusion of patients after abdominal surgery and with altered anatomy. Methods Patients with indications for deep enteroscopy were enrolled in a prospective observational multicenter study. The primary objective was the serious adverse event (SAE) rate; secondary objectives were the diagnostic and therapeutic yield, procedural success, time, and insertion depth. Data analysis was subdivided into training and core (post-training) study phases at centers with different levels of MSE experience. Results 298 patients (120 women; median age 68, range 19–92) were enrolled. In the post-training phase, 21.5 % (n = 54) had previous abdominal surgery, 10.0 % (n = 25) had surgically altered anatomy. Overall, SAEs occurred in 2.3 % (7/298; 95 %CI 0.9 %–4.8 %). The SAE rate was 2.0 % (5/251) in the core group and 4.3 % (2/47) in the training group, and was not increased after abdominal surgery (1.9 %). Total enteroscopy was achieved in half of the patients (n = 42) undergoing planned total enteroscopy. In 295/337 procedures (87.5 %), the anatomical region of interest could be reached. Conclusions This prospective multicenter study showed that MSE was feasible and safe in a large cohort of patients in a real-life setting, after a short learning curve. MSE was shown to be feasible in postsurgical patients, including those with altered anatomy, without an increase in the SAE rate.

Immune cell trafficking is a key requirement in the pathogenesis of inflammatory bowel diseases. Consistently, therapeutic strategies to target immune cell trafficking have been established and continue to be developed for the treatment of ulcerative colitis and Crohn's disease.In this review, we briefly summarize the most important checkpoints of intestinal immune cell trafficking and their importance during IBD. Moreover, we provide an overview of associated therapeutic targets and previous as well as current efforts on treatment strategies related to these targets.Finally, we comment on potential future developments that might shape the field of immune cell trafficking in the context of IBD.

Objective: The study aimed to prospectively evaluate a new molecular biomarker panel (KRAS, NRAS, BRAF, PIK3CA, and ERBB2) for palliative first-line treatment of colorectal cancer (CRC), including a multidisciplinary treatment approach. The rate of secondary metastasis resections was assessed. Patients and Methods: A total of 40 patients with definitively nonresectable metastatic CRC were enrolled from 10 centers before the interim analysis (June 2019) of the IVOPAK II trial (Interdisciplinary Care with Quality Control in Palliative Treatment of Colorectal Cancer). After determination of 5 molecular biomarkers in the tumor (KRAS, exons 2–4; NRAS, exons 2–4; BRAF V600E; PIK3CA; and ERBB2), patients in the IVOPAK II study received FOLFIRI plus cetuximab for all-RAS/quintuple-wildtype disease and FOLFIRI plus bevacizumab in the case of RAS mutations. The current article presents the early description of the clinical outcome of the interim analysis of IVOPAK II comparing the all-RAS/quintuple-wildtype and RAS-mutations populations, including a multidisciplinary-treated case report of a quintuple-wildtype patient. Results: The quintuple-wildtype population treated with FOLFIRI plus cetuximab in first-line exhibited a significantly higher response rate and enhanced early tumor shrinkage in the interim analysis than the RAS-mutations population, as well as a high rate of secondary metastatic resections. Conclusion: Initial results of this new biomarker panel (quintuple-wildtype) are promising for anti-EGFR therapy with cetuximab plus doublet chemotherapy (FOLFIRI) in first-line treatment of metastatic CRC. These results warrant confirmation with higher case numbers in the IVOPAK II trial.

Shear wave dispersion imaging is a novel ultrasound-based technique, which analyzes the speed of different shear wave components depending on their frequency. The dispersion of shear wave speed correlates with the viscosity of the liver parenchyma. The aim of this prospective study was to evaluate the use of shear wave dispersion imaging in focal liver lesions in the non-cirrhotic liver.Patients with unclear focal liver lesions in B-mode ultrasound were prospectively assigned to shear wave dispersion imaging (m/s/kHz). Measurements were conducted within the lesion and in the liver parenchyma of the right liver lobe using an intercostal window. Histology and contrast-enhanced ultrasound served as the reference for the characterization of the lesions.Out of 46 patients included in this study, 24 had liver metastases and 22 had benign liver lesions. Benign lesions consisted mostly of hemangiomas (n=12) and focal nodular hyperplasia (n=8). Malignant lesions showed significantly lower shear wave dispersion (13.0±2.45 m/s/kHz) compared to benign tumors (15.2±2.74 m/s/kHz, p0.01). In further subgroup analysis, the difference was significant for hemangiomas (15.32±2.42 m/s/kHz, p=0.04) but not for FNHs (14.98±3.36 m/s/kHz, p=0.38). The dispersion of reference liver parenchyma did not differ significantly between the groups (p=0.54).The quantification of viscosity by shear wave dispersion is a new parameter for the characterization of focal liver lesions with higher dispersion values in hemangiomas and lower dispersion values in metastases. However, it cannot differentiate reliably between benign and malignant lesions.Die Scherwellendispersion ist ein neues ultraschallbasiertes Verfahren, welches die Geschwindigkeit verschiedener Scherwellenanteile in Abhängigkeit ihrer Frequenz misst. Diese Dispersion der Scherwellen korreliert mit der Viskosität des Leberparenchyms. Ziel dieser prospektiven Studie war es, die Anwendung von Scherwellendispersion in fokalen Leberläsionen in der nichtzirrhotischen Leber zu untersuchen.Patienten mit fokalen Leberläsionen wurden prospektiv mit Scherwellendispersion (m/s/kHz) untersucht. Die Messungen wurden in der Läsion und im Parenchym des rechten Leberlappens mit interkostalem Zugang durchgeführt. Die Einordnung der Leberläsionen erfolgte mittels Kontrastmittelsonografie oder Histologie.Von insgesamt 46 eingeschlossenen Patienten hatten 24 Lebermetastasen und 22 gutartige Läsionen. Benigne Veränderungen waren vor allem Hämangiome (n=12) und fokale noduläre Hyperplasien (n=8). Metastasen zeigten eine signifikant niedrigere Dispersion (13,0±2,45m/s/kHz) als gutartige Leberläsionen (15,2±2,74m/s/kHz; p0,01). In der Subgruppenanalyse war nur der Unterschied zu Hämangiomen signifikant (15,32±2,42m/s/kHz; p=0,04), nicht aber zu FNH (14,98±3,36m/s/kHz; p=0,38). Die Messwerte des Leberparenchyms zwischen den einzelnen Gruppen waren nicht signifikant unterschiedlich (p=0,54).Die Bestimmung der Viskosität mit Scherwellendispersion ist ein neuer Parameter zur Charakterisierung fokaler Leberläsionen mit höheren Werten in Hämangiomen und niedrigeren Werten in Metastasen. Er ermöglicht jedoch keine zuverlässige Unterscheidung zwischen benignen und malignen Läsionen.