Added Value of Tomoelastography for Characterization of Pancreatic Neuroendocrine Tumor Aggressiveness Based on Stiffness

Simple Summary: The prediction of pancreatic neuroendocrine tumor (PNET) aggressiveness is important for treatment planning. The aim of this study was to evaluate the diagnostic performance of magnetic resonance elastography (MRE) with tomoelastography postprocessing (tomoelastography) in differentiating PNET from healthy pancreatic tissue and to correlate PNET stiffness with aggressiveness using asphericity derived from positron emission tomography (PET) as reference. In this prospective study we showed in a group of 13 patients with PNET that tomoelastography detected PNET by increased stiffness (p < 0.01) with a high diagnostic performance (AUC = 0.96). PNET was positively correlated with PET derived asphericity (r = 0.81). Tomoelastography provides quantitative imaging markers for the detection of PNET and the prediction of greater tumor aggressiveness by increased stiffness. Abstract: Purpose: To evaluate the diagnostic performance of tomoelastography in differentiating pancreatic neuroendocrine tumors (PNETs) from healthy pancreatic tissue and to assess the prediction of tumor aggressiveness by correlating PNET stiffness with PET derived asphericity. Methods: 13 patients with PNET were prospectively compared to 13 age-/sex-matched heathy volunteers (CTR). Multifrequency MR elastography was combined with tomoelastography-postprocessing to provide high-resolution maps of shear wave speed (SWS in m/s). SWS of pancreatic neuroendocrine tumor (PNET-T) were compared with nontumorous pancreatic tissue in patients with PNET (PNET-NT) and heathy pancreatic tissue (CTR). The diagnostic performance of tomoelastography was evaluated by ROC-AUC analysis. PNET-SWS correlations were calculated with Pearson’s r. Results: SWS was higher in PNET-T (2.02 ± 0.61 m/s) compared to PNET-NT (1.31 ± 0.18 m/s, p < 0.01) and CTR (1.26 ± 0.09 m/s, p < 0.01). An SWS-cutoff of 1.46 m/s distinguished PNET-T from PNET-NT (AUC = 0.89; sensitivity = 0.85; specificity = 0.92) and a cutoff of 1.49 m/s differentiated pancreatic tissue of CTR from PNET-T (AUC = 0.96; sensitivity = 0.92; specificity = 1.00). The SWS of PNET-T was positively correlated with PET derived asphericity (r = 0.81; p = 0.01). Conclusions: Tomoelastography provides quantitative imaging markers for the detection of PNET and the prediction of greater tumor aggressiveness by increased stiffness

On the relationship between metabolic capacities and in vivo viscoelastic properties of the liver

The liver is the central metabolic organ. It constantly adapts its metabolic capacity to current physiological requirements. However, the relationship between tissue structure and hepatic function is incompletely understood; this results in a lack of diagnostic markers in medical imaging that can provide information about the liver's metabolic capacity. Therefore, using normal rabbit livers, we combined magnetic resonance elastography (MRE) with proteomics-based kinetic modeling of central liver metabolism to investigate the potential role of MRE for predicting the liver's metabolic function in vivo. Nineteen New Zealand white rabbits were investigated by multifrequency MRE and positron emission tomography (PET). This yielded maps of shear wave speed (SWS), penetration rate (PR) and standardized uptake value (SUV). Proteomic analysis was performed after the scans. Hepatic metabolic functions were assessed on the basis of the HEPATOKIN1 model in combination with a model of hepatic lipid-droplet metabolism using liquid chromatography-mass spectrometry. Our results showed marked differences between individual livers in both metabolic functions and stiffness properties, though not in SUV. When livers were divided into 'stiff' and 'soft' subgroups (cutoff SWS = 1.6 m/s), stiff livers showed a lower capacity for triacylglycerol storage, while at the same time showing an increased capacity for gluconeogenesis and cholesterol synthesis. Furthermore, SWS was correlated with gluconeogenesis and PR with urea production and glutamine exchange. In conclusion, our study indicates a close relationship between the viscoelastic properties of the liver and metabolic function. This could be used in future studies to predict non-invasively the functional reserve capacity of the liver in patients

Feasibility of Intestinal MR Elastography in Inflammatory Bowel Disease

Background: While MR enterography allows detection of inflammatory bowel disease (IBD), the findings continue to be of limited use in guiding treatment-medication vs. surgery. Purpose: To test the feasibility of MR elastography of the gut in healthy volunteers and IBD patients. Study type: Prospective pilot. Population: Forty subjects (healthy volunteers: n = 20, 37 ± 14 years, 10 women; IBD patients: n = 20 (ulcerative colitis n = 9, Crohn's disease n = 11), 41 ± 15 years, 11 women). Field strength/sequence: Multifrequency MR elastography using a single-shot spin-echo echo planar imaging sequence at 1.5 T with drive frequencies of 40, 50, 60, and 70 Hz. Assessment: Maps of shear-wave speed (SWS, in m/s) and loss angle (φ, in rad), representing stiffness and solid-fluid behavior, respectively, were generated using tomoelastography data processing. Histopathological analysis of surgical specimens was used as reference standard in patients. Statistical tests: Unpaired t-test, one-way analysis of variance followed by Tukey post hoc analysis, Pearson's correlation coefficient and area under the receiver operating characteristic curve (AUC) with 95%-confidence interval (CI). Significance level of 5%. Results: MR elastography was feasible in all 40 subjects (100% technical success rate). SWS and φ were significantly increased in IBD by 21% and 20% (IBD: 1.45 ± 0.14 m/s and 0.78 ± 0.12 rad; healthy volunteers: 1.20 ± 0.14 m/s and 0.65 ± 0.06 rad), whereas no significant differences were found between ulcerative colitis and Crohn's disease (P = 0.74 and 0.90, respectively). In a preliminary assessment, a high diagnostic accuracy in detecting IBD was suggested by an AUC of 0.90 (CI: 0.81-0.96) for SWS and 0.84 (CI: 0.71-0.95) for φ. Data conclusion: In this pilot study, our results demonstrated the feasibility of MR elastography of the gut and showed an excellent diagnostic performance in predicting IBD. Evidence level: 1 TECHNICAL EFFICACY: Stage 1

Tomoelastography for Longitudinal Monitoring of Viscoelasticity Changes in the Liver and in Renal Allografts after Direct-Acting Antiviral Treatment in 15 Kidney Transplant Recipients with Chronic HCV Infection

Besides the liver, hepatitis C virus (HCV) infection also affects kidney allografts. The aim of this study was to longitudinally evaluate viscoelasticity changes in the liver and in kidney allografts in kidney transplant recipients (KTRs) with HCV infection after treatment with direct-acting antiviral agents (DAAs). Fifteen KTRs with HCV infection were treated with DAAs (daclatasvir and sofosbuvir) for 3 months and monitored at baseline, end of treatment (EOT), and 3 (FU1) and 12 (FU2) months after EOT. Shear-wave speed (SWS) and loss angle of the complex shear modulus (φ), reflecting stiffness and fluidity, respectively, were reconstructed from multifrequency magnetic resonance elastography data with tomoelastography post-processing. After virus elimination by DAAs, hepatic stiffness and fluidity decreased, while kidney allograft stiffness and fluidity increased compared with baseline (hepatic stiffness change at FU1: -0.14 m/s, p < 0.01, and at FU2: -0.11 m/s, p < 0.05; fluidity at FU1: -0.05 rad, p = 0.04 and unchanged at FU2: p = 0.20; kidney allograft stiffness change at FU1: +0.27 m/s, p = 0.01, and at FU2: +0.30 m/s, p < 0.01; fluidity at FU1 and FU2: +0.06 rad, p = 0.02). These results suggest the restoration of mechanically sensitive structures and functions in both organs. Tomoelastography can be used to monitor the therapeutic results of HCV treatment non-invasively on the basis of hepatic and renal viscoelastic parameters

A prospective study of daclatasvir and sofosbuvir in chronic HCV-infected kidney transplant recipients

Abstract Background Only a few prospective trials exist regarding the use of novel direct-acting antiviral agents (DAAs) in kidney transplant recipients (KTR) with chronic hepatitis C virus (HCV) infection. Methods This prospective single-center trial evaluated treatment with daclatasvir (DCV) and sofosbuvir (SOF) over 12 weeks in 16 adult chronic HCV infected KTR and eGFR > 30 ml/min/1.73m2. Primary endpoint was sustained virological response 12 weeks after end of therapy (SVR12). Beside baseline liver biopsy, hepatic function and glucose metabolism were regularly assessed. Results Four of 16 study patients had previously failed interferon-based HCV treatment. Liver biopsy showed mostly moderate fibrosis score before therapy with DCV/SOF was initiated at a median of 10.3 years after transplantation. In total, 15 of 16 KTR achieved SVR12. One patient showed early viral relapse because of resistance-associated variants (RAVs) in the HCV NS5A region. Rescue treatment with SOF/velpatasvir/voxilaprevir resulted in SVR12. DAAs treatment led to significant improvement of liver metabolism and glucose tolerance accompanied with no therapy-associated major adverse events and excellent tolerability. Conclusions Our study demonstrates safety, efficacy and functional benefit of DCV/SOF treatment in KTR with chronic HCV infection. We provide data on rescue strategies for treatment failures due to present RAVs and amelioration of hepatic function and glucose tolerance. Trial registration Registry name: European Clinical Trials Register; Trial registry number (Eudra-CT): 2014–004551-32, Registration date: Aug 28th 2015

Outcomes of Deceased Donor Kidney Transplantation in the Eurotransplant Senior Program with A Focus on Recipients ≥75 Years

To evaluate the outcomes of kidney transplantations (KTs) in the Eurotransplant Senior Program (ESP) with a focus on the very old, defined as recipients ≥75 years. This retrospective clinical study included 85 patients, who under the ESP protocol underwent deceased donor kidney transplantation from January 2010 to July 2018 at the Charité–Universitätsmedizin Berlin in Germany. Recipients were divided in three age groups, i.e., Group 65–69, Group 70–74, Group ≥75, and compared. Prognostic risk factors for short and long-term outcomes of kidney transplantations were investigated. Graft survival at 1 and 5 years were respectively 90.7% and 68.0% for group 65–69, 88.9% and 76.2% for Group 70–74, and 100% and 71.4% for Group ≥75. Patient survival at 1 and 5 years were respectively 92.9% and 68.0% for Group 65–69, 85.7% and 61.5% for Group 70–74 and 100% and 62.5% for Group ≥75. Serum creatinine did not significantly differ between the three groups, with the exception of serum creatinine at 1 year. Increased recipient age and prolonged time on dialysis correlated with increased occurrence of postoperative complication. An increase in BMI, pretransplant diabetes mellitus and prolonged time on dialysis correlated with the occurrence of delayed graft function (DGF). History of smoking was identified as an independent risk factor for events of rejection. Increased human leukocyte antigen mismatches (HLA-MM) and prolonged cold ischemia time (CIT) correlated with higher rates of intensive care unit (ICU) treatment. This study supports kidney transplantations for the very old. End-stage renal disease (ESRD) patients ≥75 years of age who underwent kidney transplantation experienced comparable results to their younger counterparts. A comprehensive evaluation of ESRD patients with consideration of prognostic risk factor is the most suitable mean of identifying adequate kidney transplant candidates