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30 Publications visible to you, out of a total of 30
Effect of Post-mortem Interval and Perfusion on the Biophysical Properties of ex vivo Liver Tissue Investigated Longitudinally by MRE and DWI.

Abstract (Expand)

Structural changes of soft tissues on the cellular level can be characterized by histopathology, but not longitudinally in the same tissue. Alterations of cellular structures and tissue matrix are … associated with changes in biophysical properties which can be monitored longitudinally by quantitative diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE). In this work, DWI and MRE examinations were performed in a 0.5-Tesla compact scanner to investigate longitudinal changes in water diffusivity, stiffness and viscosity of ex-vivo rat livers for up to 20 h post-mortem (pm). The effect of blood on biophysical parameters was examined in 13 non-perfused livers (containing blood, NPLs) and 14 perfused livers (blood washed out, PLs). Changes in cell shape, cell packing and cell wall integrity were characterized histologically. In all acquisitions, NPLs presented with higher shear-wave speed (c), higher shear-wave penetration rate (a) and smaller apparent-diffusion-coefficients (ADCs) than PL. Time-resolved analysis revealed three distinct phases: (i) an initial phase (up to 2 h pm) with markedly increased c and a and reduced ADCs; (ii) an extended phase with relatively stable values; and (iii) a degradation phase characterized by significant increases in a (10 h pm in NPLs and PLs) and ADCs (10 h pm in NPLs, 13 h pm in PLs). Histology revealed changes in cell shape and packing along with decreased cell wall integrity, indicating tissue degradation in NPLs and PLs 10 h pm. Taken together, our results demonstrate that the biophysical properties of fresh liver tissue rapidly change within 2 h pm, which seems to be an effect of both cytotoxic edema and vascular blood content. Several hours later, disruption of cell walls resulted in higher water diffusivity and wave penetration. These results reveal the individual contributions of vascular components and cellular integrity to liver elastography and provide a biophysical, imaging-based fingerprint of liver tissue degradation.

Authors: K. Garczynska, H. Tzschatzsch, S. Assili, A. A. Kuhl, A. Hackel, E. Schellenberger, N. Berndt, H. G. Holzhutter, J. Braun, I. Sack, J. Guo

Date Published: 20th Aug 2021

Publication Type: Journal

Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis.

Abstract (Expand)

Alzheimer's disease (AD) is frequently accompanied by progressing weight loss, correlating with mortality. Counter-intuitively, weight loss in old age might predict AD onset but obesity in midlife … increases AD risk. Furthermore, AD is associated with diabetes-like alterations in glucose metabolism. Here, we investigated metabolic features of amyloid precursor protein overexpressing APP23 female mice modeling AD upon long-term challenge with high-sucrose (HSD) or high-fat diet (HFD). Compared to wild type littermates (WT), APP23 females were less prone to mild HSD-induced and considerable HFD-induced glucose tolerance deterioration, despite unaltered glucose tolerance during normal-control diet. Indirect calorimetry revealed increased energy expenditure and hyperactivity in APP23 females. Dietary interventions, especially HFD, had weaker effects on lean and fat mass gain, steatosis and adipocyte hypertrophy of APP23 than WT mice, as shown by (1)H-magnetic-resonance-spectroscopy, histological and biochemical analyses. Proteome analysis revealed differentially regulated expression of mitochondrial proteins in APP23 livers and brains. In conclusion, hyperactivity, increased metabolic rate, and global mitochondrial dysfunction potentially add up to the development of AD-related body weight changes in APP23 females, becoming especially evident during diet-induced metabolic challenge. These findings emphasize the importance of translating this metabolic phenotyping into human research to decode the metabolic component in AD pathogenesis.

Authors: S. Schreyer, N. Berndt, J. Eckstein, M. Mulleder, S. Hemmati-Sadeghi, C. Klein, B. Abuelnor, A. Panzel, D. Meierhofer, J. Spranger, B. Steiner, S. Brachs

Date Published: 16th Apr 2021

Publication Type: Journal

Computational Hypothesis: How Intra-Hepatic Functional Heterogeneity May Influence the Cascading Progression of Free Fatty Acid-Induced Non-Alcoholic Fatty Liver Disease (NAFLD).

Abstract (Expand)

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common type of chronic liver disease in developed nations, affecting around 25% of the population. Elucidating the factors causing NAFLD in individual … patients to progress in different rates and to different degrees of severity, is a matter of active medical research. Here, we aim to provide evidence that the intra-hepatic heterogeneity of rheological, metabolic and tissue-regenerating capacities plays a central role in disease progression. We developed a generic mathematical model that constitutes the liver as ensemble of small liver units differing in their capacities to metabolize potentially cytotoxic free fatty acids (FFAs) and to repair FFA-induced cell damage. Transition from simple steatosis to more severe forms of NAFLD is described as self-amplifying process of cascading liver failure, which, to stop, depends essentially on the distribution of functional capacities across the liver. Model simulations provided the following insights: (1) A persistently high plasma level of FFAs is sufficient to drive the liver through different stages of NAFLD; (2) Presence of NAFLD amplifies the deleterious impact of additional tissue-damaging hits; and (3) Coexistence of non-steatotic and highly steatotic regions is indicative for the later occurrence of severe NAFLD stages.

Authors: H. G. Holzhutter, N. Berndt

Date Published: 5th Mar 2021

Publication Type: Journal

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.

Abstract (Expand)

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 (phi), 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.

Authors: S. R. Marticorena Garcia, C. E. Althoff, M. Durr, F. Halleck, K. Budde, U. Grittner, C. Burkhardt, K. Johrens, J. Braun, T. Fischer, B. Hamm, I. Sack, J. Guo

Date Published: 1st Feb 2021

Publication Type: Journal

Changes in Liver Mechanical Properties and Water Diffusivity During Normal Pregnancy Are Driven by Cellular Hypertrophy.

Abstract (Expand)

During pregnancy, the body's hyperestrogenic state alters hepatic metabolism and synthesis. While biochemical changes related to liver function during normal pregnancy are well understood, … pregnancy-associated alterations in biophysical properties of the liver remain elusive. In this study, we investigated 26 ex vivo fresh liver specimens harvested from pregnant and non-pregnant rats by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) in a 0.5-Tesla compact magnetic resonance imaging (MRI) scanner. Water diffusivity and viscoelastic parameters were compared with histological data and blood markers. We found livers from pregnant rats to have (i) significantly enlarged hepatocytes (26 +/- 15%, p < 0.001), (ii) increased liver stiffness (12 +/- 15%, p = 0.012), (iii) decreased viscosity (-23 +/- 14%, p < 0.001), and (iv) increased water diffusivity (12 +/- 11%, p < 0.001). In conclusion, increased stiffness and reduced viscosity of the liver during pregnancy are mainly attributable to hepatocyte enlargement. Hypertrophy of liver cells imposes fewer restrictions on intracellular water mobility, resulting in a higher hepatic water diffusion coefficient. Collectively, MRE and DWI have the potential to inform on structural liver changes associated with pregnancy in a clinical context.

Authors: K. Garczynska, H. Tzschatzsch, A. A. Kuhl, A. S. Morr, L. Lilaj, A. Hackel, E. Schellenberger, N. Berndt, H. G. Holzhutter, J. Braun, I. Sack, J. Guo

Date Published: 17th Dec 2020

Publication Type: Journal

Reduction of breathing artifacts in multifrequency magnetic resonance elastography of the abdomen.

Abstract (Expand)

PURPOSE: With abdominal magnetic resonance elastography (MRE) often suffering from breathing artifacts, it is recommended to perform MRE during breath-hold. However, breath-hold acquisition prohibits … extended multifrequency MRE examinations and yields inconsistent results when patients cannot hold their breath. The purpose of this work was to analyze free-breathing strategies in multifrequency MRE of abdominal organs. METHODS: Abdominal MRE with 30, 40, 50, and 60 Hz vibration frequencies and single-shot, multislice, full wave-field acquisition was performed four times in 11 healthy volunteers: once with multiple breath-holds and three times during free breathing with ungated, gated, and navigated slice adjustment. Shear wave speed maps were generated by tomoelastography inversion. Image registration was applied for correction of intrascan misregistration of image slices. Sharpness of features was quantified by the variance of the Laplacian. RESULTS: Total scan times ranged from 120 seconds for ungated free-breathing MRE to 376 seconds for breath-hold examinations. As expected, free-breathing MRE resulted in larger organ displacements (liver, 4.7 +/- 1.5 mm; kidneys, 2.4 +/- 2.2 mm; spleen, 3.1 +/- 2.4 mm; pancreas, 3.4 +/- 1.4 mm) than breath-hold MRE (liver, 0.7 +/- 0.2 mm; kidneys, 0.4 +/- 0.2 mm; spleen, 0.5 +/- 0.2 mm; pancreas, 0.7 +/- 0.5 mm). Nonetheless, breathing-related displacement did not affect mean shear wave speed, which was consistent across all protocols (liver, 1.43 +/- 0.07 m/s; kidneys, 2.35 +/- 0.21 m/s; spleen, 2.02 +/- 0.15 m/s; pancreas, 1.39 +/- 0.15 m/s). Image registration before inversion improved the quality of free-breathing examinations, yielding no differences in image sharpness to uncorrected breath-hold MRE in most organs (P > .05). CONCLUSION: Overall, multifrequency MRE is robust to breathing when considering whole-organ values. Respiration-related blurring can readily be corrected using image registration. Consequently, ungated free-breathing MRE combined with image registration is recommended for multifrequency MRE of abdominal organs.

Authors: M. Shahryari, T. Meyer, C. Warmuth, H. Herthum, G. Bertalan, H. Tzschatzsch, L. Stencel, S. Lukas, L. Lilaj, J. Braun, I. Sack

Date Published: 26th Oct 2020

Publication Type: Journal

Metabolic heterogeneity of human hepatocellular carcinoma: implications for personalized pharmacological treatment.

Abstract (Expand)

Metabolic reprogramming is a characteristic feature of cancer cells, but there is no unique metabolic program for all tumors. Genetic and gene expression studies have revealed heterogeneous inter- and … intratumor patterns of metabolic enzymes and membrane transporters. The functional implications of this heterogeneity remain often elusive. Here, we applied a systems biology approach to gain a comprehensive and quantitative picture of metabolic changes in individual hepatocellular carcinoma (HCC). We used protein intensity profiles determined by mass spectrometry in samples of 10 human HCCs and the adjacent noncancerous tissue to calibrate Hepatokin1, a complex mathematical model of liver metabolism. We computed the 24-h profile of 18 metabolic functions related to carbohydrate, lipid, and nitrogen metabolism. There was a general tendency among the tumors toward downregulated glucose uptake and glucose release albeit with large intertumor variability. This finding calls into question that the Warburg effect dictates the metabolic phenotype of HCC. All tumors comprised elevated beta-oxidation rates. Urea synthesis was found to be consistently downregulated but without compromising the tumor's capacity for ammonia detoxification owing to increased glutamine synthesis. The largest intertumor heterogeneity was found for the uptake and release of lactate and the size of the cellular glycogen content. In line with the observed metabolic heterogeneity, the individual HCCs differed largely in their vulnerability against pharmacological treatment with metformin. Taken together, our approach provided a comprehensive and quantitative characterization of HCC metabolism that may pave the way for a computational a priori assessment of pharmacological therapies targeting metabolic processes of HCC.

Authors: N. Berndt, J. Eckstein, N. Heucke, T. Wuensch, R. Gajowski, M. Stockmann, D. Meierhofer, H. G. Holzhutter

Date Published: 8th Oct 2020

Publication Type: Journal

Tomoelastography for Measurement of Tumor Volume Related to Tissue Stiffness in Pancreatic Ductal Adenocarcinomas.

Abstract (Expand)

OBJECTIVES: Estimations of tumor volume and boundary in pancreatic ductal adenocarcinoma (PDAC) are crucial for surgery planning. The aim of the study is to evaluate tomoelastography for detection of … PDAC and quantification of PDAC volume based on tissue stiffness. MATERIALS AND METHODS: From March 2018 to December 2019, a total of 102 participants (30 healthy participants and 72 patients with histologically proven PDAC) were prospectively enrolled in a multicenter study. Multifrequency magnetic resonance elastography was combined with tomoelastography postprocessing to generate maps of shear wave speed (SWS) depicting highly resolved anatomical details of tissue stiffness. Subregional analysis of pancreatic head, body, and tail and reproducibility tests were performed in healthy participants, whereas tumorous (PDAC-T) and nontumorous (PDAC-NT) pancreatic tissue analysis was conducted in patients. In all patients, tumor volumes measured by computed tomography (CT) were compared with SWS-derived volumes. In addition, in 32 patients, tumor sizes were evaluated by macroscopy after resection. RESULTS: Tumor volumes were quantified in 99% and 87% of all cases with tomoelastography and CT, respectively. Pancreatic SWS was highly reproducible (repeatability coefficient = 0.12) and did not vary regionally or with patient age, sex, or body mass index (all P > 0.08). Shear wave speed was higher in PDAC-T (2.08 +/- 0.38 m/s) than in healthy (1.25 +/- 0.09 m/s; P < 0.001) and PDAC-NT (1.28 +/- 0.14 m/s; P < 0.001) participants. A threshold of 1.47 m/s separated PDAC-T from healthy volunteers (area under the curve = 1.0, sensitivity = 100%, specificity = 100%), while 1.49 m/s separated PDAC-T from PDAC-NT with high accuracy (area under the curve = 0.99, sensitivity = 90%, specificity = 100%). Tomoelastography-derived tumor volume correlated with CT volume (r = 0.91, P < 0.001) and ex vivo tumor volume (r = 0.66, P < 0.001). CONCLUSIONS: Tomoelastography provides a quantitative imaging marker for tissue stiffness depicting PDAC boundaries and separates PDAC from unaffected pancreatic tissue.

Authors: S. R. Marticorena Garcia, L. Zhu, E. Gultekin, R. Schmuck, C. Burkhardt, M. Bahra, D. Geisel, M. Shahryari, J. Braun, B. Hamm, Z. Y. Jin, I. Sack, J. Guo

Date Published: 17th Aug 2020

Publication Type: Journal

Functional consequences of metabolic zonation in murine livers: New insights for an old story.

Abstract (Expand)

BACKGROUND & AIMS: Zone-dependent differences in the expression of metabolic enzymes along the porto-central axis of the acinus are a long-known feature of liver metabolism. A prominent example is … the preferential localization of the enzyme glutamine synthetase in pericentral hepatocytes, where it converts potentially toxic ammonia to the valuable amino acid glutamine. However, with the exception of a few key regulatory enzymes, a comprehensive and quantitative assessment of zonal differences in the abundance of metabolic enzymes and much more importantly, an estimation of the associated functional differences between portal and central hepatocytes is missing thus far. APPROACH & RESULTS: We addressed this problem by establishing a new method for the separation of periportal and pericentral hepatocytes that yields sufficiently pure fractions of both cell populations. Quantitative shotgun proteomics identified hundreds of differentially expressed enzymes in the two cell populations. We used zone-specific proteomics data for scaling of the maximal activities to generate portal and central instantiations of a comprehensive kinetic model of central hepatic metabolism (Hepatokin1). CONCLUSION: The model simulations revealed significant portal-to-central differences in almost all metabolic pathways involving carbohydrates, fatty acids, amino acids and detoxification.

Authors: N. Berndt, E. Kolbe, R. Gajowski, J. Eckstein, F. Ott, D. Meierhofer, H. G. Holzhutter, M. Matz-Soja

Date Published: 14th Apr 2020

Publication Type: Not specified

Protein modification with ISG15 blocks coxsackievirus pathology by antiviral and metabolic reprogramming.

Abstract (Expand)

Protein modification with ISG15 (ISGylation) represents a major type I IFN-induced antimicrobial system. Common mechanisms of action and species-specific aspects of ISGylation, however, are still ill … defined and controversial. We used a multiphasic coxsackievirus B3 (CV) infection model with a first wave resulting in hepatic injury of the liver, followed by a second wave culminating in cardiac damage. This study shows that ISGylation sets nonhematopoietic cells into a resistant state, being indispensable for CV control, which is accomplished by synergistic activity of ISG15 on antiviral IFIT1/3 proteins. Concurrent with altered energy demands, ISG15 also adapts liver metabolism during infection. Shotgun proteomics, in combination with metabolic network modeling, revealed that ISG15 increases the oxidative capacity and promotes gluconeogenesis in liver cells. Cells lacking the activity of the ISG15-specific protease USP18 exhibit increased resistance to clinically relevant CV strains, therefore suggesting that stabilizing ISGylation by inhibiting USP18 could be exploited for CV-associated human pathologies.

Authors: M. Kespohl, C. Bredow, K. Klingel, M. Voss, A. Paeschke, M. Zickler, W. Poller, Z. Kaya, J. Eckstein, H. Fechner, J. Spranger, M. Fahling, E. K. Wirth, L. Radoshevich, F. Thery, F. Impens, N. Berndt, K. P. Knobeloch, A. Beling

Date Published: 21st Mar 2020

Publication Type: Not specified

Magnetic resonance elastography quantification of the solid-to-fluid transition of liver tissue due to decellularization.

Abstract (Expand)

Maintenance of tissue extracellular matrix (ECM) and its biomechanical properties for tissue engineering is one of the substantial challenges in the field of decellularization and recellularization. … Preservation of the organ-specific biomatrix is crucial for successful recellularization to support cell survival, proliferation, and functionality. However, understanding ECM properties with and without its inhabiting cells as well as the transition between the two states lacks appropriate test methods capable of quantifying bulk viscoelastic parameters in soft tissues. We used compact magnetic resonance elastography (MRE) with 400, 500, and 600 Hz driving frequency to investigate rat liver specimens for quantification of viscoelastic property changes resulting from decellularization. Tissue structures in native and decellularized livers were characterized by collagen and elastin quantification, histological analysis, and scanning electron microscopy. Decellularization did not affect the integrity of microanatomy and structural composition of liver ECM but was found to be associated with increases in the relative amounts of collagen by 83-fold (37.4 +/- 17.5 vs. 0.5 +/- 0.01 mug/mg, p = 0.0002) and elastin by approx. 3-fold (404.1 +/- 139.6 vs. 151.0 +/- 132.3 mug/mg, p = 0.0046). Decellularization reduced storage modulus by approx. 9-fold (from 4.9 +/- 0.8 kPa to 0.5 +/- 0.5 kPa, p < 0.0001) and loss modulus by approx. 7-fold (3.6 kPa to 0.5 kPa, p < 0.0001), indicating a marked loss of global tissue rigidity as well as a property shift from solid towards more fluid tissue behavior (p = 0.0097). Our results suggest that the rigidity of liver tissue is largely determined by cellular components, which are replaced by fluid-filled spaces when cells are removed. This leads to an overall increase in tissue fluidity and a viscous drag within the relatively sparse remaining ECM. Compact MRE is an excellent tool for quantifying the mechanical properties of decellularized biological tissue and a promising candidate for useful applications in tissue engineering.

Authors: H. Everwien, A. Ariza de Schellenberger, N. Haep, H. Tzschatzsch, J. Pratschke, I. M. Sauer, J. Braun, K. H. Hillebrandt, I. Sack

Date Published: 17th Mar 2020

Publication Type: Not specified

A novel variant of the (13)C-methacetin liver function breath test that eliminates the confounding effect of individual differences in systemic CO2 kinetics.

Abstract (Expand)

The principle of dynamic liver function breath tests is founded on the administration of a (13)C-labeled drug and subsequent monitoring of (13)CO2 in the breath, quantified as time series delta over … natural baseline (13)CO2 (DOB) liberated from the drug during hepatic CYP-dependent detoxification. One confounding factor limiting the diagnostic value of such tests is that only a fraction of the liberated (13)CO2 is immediately exhaled, while another fraction is taken up by body compartments from which it returns with delay to the plasma. The aims of this study were to establish a novel variant of the methacetin-based breath test LiMAx that allows to estimate and to eliminate the confounding effect of systemic (13)CO2 distribution on the DOB curve and thus enables a more reliable assessment of the hepatic detoxification capacity compared with the conventional LiMAx test. We designed a new test variant (named "2DOB") consisting of two consecutive phases. Phase 1 is initiated by the intravenous administration of (13)C-bicarbonate. Phase 2 starts about 30 min later with the intravenous administration of the (13)C-labelled test drug. Using compartment modelling, the resulting 2-phasic DOB curve yields the rate constants for the irreversible elimination and the reversible exchange of plasma (13)CO2 with body compartments (phase 1) and for the detoxification and exchange of the drug with body compartments (phase 2). We carried out the 2DOB test with the test drug (13)C-methacetin in 16 subjects with chronic liver pathologies and 22 normal subjects, who also underwent the conventional LiMAx test. Individual differences in the systemic CO2 kinetics can lead to deviations up to a factor of 2 in the maximum of DOB curves (coefficient of variation CV approximately 0.2) which, in particular, may hamper the discrimination between subjects with normal or mildly impaired detoxification capacities. The novel test revealed that a significant portion of the drug is not immediately metabolized, but transiently taken up into a storage compartment. Intriguingly, not only the hepatic detoxification rate but also the storage capacity of the drug, turned out to be indicative for a normal liver function. We thus used both parameters to define a scoring function which yielded an excellent disease classification (AUC = 0.95) and a high correlation with the MELD score (RSpearman = 0.92). The novel test variant 2DOB promises a significant improvement in the assessment of impaired hepatic detoxification capacity. The suitability of the test for the reliable characterization of the natural history of chronic liver diseases (fatty liver-fibrosis-cirrhosis) has to be assessed in further studies.

Authors: H. G. Holzhutter, T. Wuensch, R. Gajowski, N. Berndt, S. Bulik, D. Meierhofer, M. Stockmann

Date Published: 6th Feb 2020

Publication Type: Not specified

Ultrasound Time-Harmonic Elastography of the Pancreas: Reference Values and Clinical Feasibility.

Abstract (Expand)

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a very low 5-year survival rate of 8%. The aims of this study are to determine reference values and physiologic … confounders in healthy pancreas and to assess the diagnostic accuracy of ultrasound time-harmonic elastography (THE) in the detection of PDAC. MATERIALS AND METHODS: From March 2017 through May 2019, a total of 54 study participants with healthy pancreas (n = 33, CTR) or PDAC (n = 21) were prospectively enrolled. Repeatability of THE was tested in a CTR subgroup (n = 5) undergoing repeat measurement on 4 different days. Interobserver variability was analyzed in 10 healthy volunteers. Age-matched and sex-matched subgroups of CTR (n = 13) and PDAC (n = 13) were compared. In participants with histopathologically proven PDAC, measurements were performed separately in tumorous (PDAC-T) and nontumorous pancreatic tissue (PDAC-NT). Diagnostic performance of pancreatic THE was assessed by receiver operating characteristic curve analysis. RESULTS: Time-harmonic elastography was highly repeatable (intraclass correlation coefficient, 0.99), and interobserver agreement was excellent (intraclass correlation coefficient, 0.97). Shear wave speed (SWS) of PDAC-T (mean [95% confidence interval] in meters per second, 1.88 +/- 0.07 [1.84-1.92]) was higher than SWS of CTR (1.63 +/- 0.04 [1.60-1.66], P < 0.001) and PDAC-NT (1.59 +/- 0.03 [1.57-1.61], P < 0.001). The exploratory diagnostic performance of THE in separating PDAC-T was excellent (area under the receiver operating characteristic curve, 1.0). Tumorous pancreatic ductal adenocarcinoma was distinguished from CTR and PDAC-NT with cutoff values of 1.73 m/s and 1.70 m/s, respectively. CONCLUSIONS: Pancreatic ultrasound THE has high repeatability and provides excellent imaging contrast based on SWS, allowing detection of PDAC without overlap to nontumorous pancreatic tissue.

Authors: C. Burkhardt, H. Tzschatzsch, R. Schmuck, M. Bahra, C. Jurgensen, U. Pelzer, B. Hamm, J. Braun, I. Sack, S. R. Marticorena Garcia

Date Published: 28th Jan 2020

Publication Type: Journal

Resection of hepatic and pulmonary metastasis from metastatic esophageal and gastric cancer: a nationwide study.

Abstract (Expand)

The standard of care for gastroesophageal cancer patients with hepatic or pulmonary metastases is best supportive care or palliative chemotherapy. Occasionally, patients can be selected for curative … treatment instead. This study aimed to evaluate patients who underwent a resection of hepatic or pulmonary metastasis with curative intent. The Dutch national registry for histo- and cytopathology was used to identify these patients. Data were retrieved from the individual patient files. Kaplan-Meier survival analysis was performed. Between 1991 and 2016, 32,057 patients received a gastrectomy or esophagectomy for gastroesophageal cancer in the Netherlands. Of these patients, 34 selected patients received a resection of hepatic metastasis (n = 19) or pulmonary metastasis (n = 15) in 21 different hospitals. Only 4 patients received neoadjuvant therapy before metastasectomy. The majority of patients had solitary, metachronous metastases. After metastasectomy, grade 3 (Clavien-Dindo) complications occurred in 7 patients and mortality in 1 patient. After resection of hepatic metastases, the median potential follow-up time was 54 months. Median overall survival (OS) was 28 months and the 1-, 3-, and 5- year OS was 84%, 41%, and 31%, respectively. After pulmonary metastases resection, the median potential follow-up time was 80 months. The median OS was not reached and the 1-, 3-, and 5- year OS was 67%, 53%, and 53%, respectively. In selected patients with gastroesophageal cancer with hepatic or pulmonary metastases, metastasectomy was performed with limited morbidity and mortality and offered a 5-year OS of 31-53%. Further prospective studies are required.

Authors: M. F. J. Seesing, A. van der Veen, H. J. F. Brenkman, H. B. A. C. Stockmann, G. A. P. Nieuwenhuijzen, C. Rosman, F. J. H. van den Wildenberg, M. I. van Berge Henegouwen, P. van Duijvendijk, B. P. L. Wijnhoven, J. H. M. B. Stoot, M. Lacle, J. P. Ruurda, R. van Hillegersberg

Date Published: 31st Dec 2019

Publication Type: Not specified

Dynamic liver function is an independent predictor of recurrence-free survival after curative liver resection for HCC - A retrospective cohort study.

Abstract (Expand)

BACKGROUND: Hepatocellular carcinoma is the fifth most prevalent cancer worldwide. High tumour recurrence is the most common cause of the impaired 5-year survival rate of 26-58% after hepatectomy. The … aim of this study was to investigate the impact of preoperative dynamic liver function on long-term outcome. MATERIALS AND METHODS: A total of 146 patients that underwent curative resection for HCC at our department from 2005 to 2016 were analysed. Univariate analysis was calculated using Kaplan-Meier method. Multivariable analysis was carried out with Cox regression. RESULTS: The cumulative 1-, 3-, 5-year survival rates were 83%, 42% and 14%, respectively. Multivariable Cox regression yielded that overall survival depends on disease recurrence, haemoglobin, number of tumours, liver cirrhosis, lymphatic vessel invasion, UICC stage and postoperative complications. The corresponding 1-, 3-, 5-year disease-free survival rates were 73%, 32% and 10%, respectively. Multivariable analysis yielded preoperative liver function capacity (HR 2.421; p=0.014), vascular invasion (HR 2.116; p=0.034) and UICC stage (HR 2.200; p=0.037) as risk factors associated with disease-free survival. A subanalysis with respect to the degree of functional impairment implicated that severity of liver function impairment is correlated with the disease-free survival rate. CONCLUSION: This study shows that preoperative dynamic liver function assessed by LiMAx test as well as severity of underlying liver disease have a significant impact on recurrence-free survival after curative hepatectomy. Patients presenting with impaired liver function should be evaluated for other treatment e.g. liver transplantation or receive closer oncological follow-up.

Authors: E. Bluthner, J. Bednarsch, M. Malinowski, P. Binder, J. Pratschke, M. Stockmann, M. Kaffarnik

Date Published: 9th Sep 2019

Publication Type: Not specified

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