@article{BanalesCardinaleCarpinoetal.2016, author = {Banales, Jesus M. and Cardinale, Vincenzo and Carpino, Guido and Marzioni, Marco and Andersen, Jesper B. and Invernizzi, Pietro and Lind, Guro E. and Folseraas, Trine and Forbes, Stuart J. and Fouassier, Laura and Geier, Andreas and Calvisi, Diego F. and Mertens, Joachim C. and Trauner, Michael and Benedetti, Antonio and Maroni, Luca and Vaquero, Javier and Macias, Rocio I. R. and Raggi, Chiara and Perugorria, Maria J. and Gaudio, Eugenio and Boberg, Kirsten M. and Marin, Jose J. G. and Alvaro, Domenico}, title = {Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)}, series = {Nature Reviews Gastroenterology \& Hepatology}, volume = {13}, journal = {Nature Reviews Gastroenterology \& Hepatology}, number = {5}, doi = {10.1038/nrgastro.2016.51}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189077}, pages = {261-280}, year = {2016}, abstract = {Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.}, language = {en} } @article{RaselliHearnWyssetal.2019, author = {Raselli, Tina and Hearn, Tom and Wyss, Annika and Atrott, Kirstin and Peter, Alain and Frey-Wagner, Isabelle and Spalinger, Marianne R. and Maggio, Ewerton M. and Sailer, Andreas W. and Schmitt, Johannes and Schreiner, Philipp and Moncsek, Anja and Mertens, Joachim and Scharl, Michael and Griffiths, William J. and Bueter, Marco and Geier, Andreas and Rogler, Gerhard and Wang, Yuqin and Misselwitz, Benjamin}, title = {Elevated oxysterol levels in human and mouse livers reflect nonalcoholic steatohepatitis}, series = {Journal of Lipid Research}, volume = {60}, journal = {Journal of Lipid Research}, number = {7}, doi = {10.1194/jlr.M093229}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225004}, pages = {1270-1283}, year = {2019}, abstract = {Nonalcoholic steatohepatitis (NASH), a primary cause of liver disease, leads to complications such as fibrosis, cirrhosis, and carcinoma, but the pathophysiology of NASH is incompletely understood. Epstein-Barr virus-induced G protein-coupled receptor 2 (EBI2) and its oxysterol ligand 7 alpha,25-dihydroxycholesterol (7 alpha,25-diHC) are recently discovered immune regulators. Several lines of evidence suggest a role of oxysterols in NASH pathogenesis, but rigorous testing has not been performed. We measured oxysterol levels in the livers of NASH patients by LC-MS and tested the role of the EBI2-7 alpha,25-diHC system in a murine feeding model of NASH. Free oxysterol profiling in livers from NASH patients revealed a pronounced increase in 24- and 7-hydroxylated oxysterols in NASH compared with controls. Levels of 24- and 7-hydroxylated oxysterols correlated with histological NASH activity. Histological analysis of murine liver samples demonstrated ballooning and liver inflammation. No significant genotype-related differences were observed in Ebi2(-/-) mice and mice with defects in the 7 alpha,25-diHC synthesizing enzymes CH25H and CYP7B1 compared with wild-type littermate controls, arguing against an essential role of these genes in NASH pathogenesis. Elevated 24- and 7-hydroxylated oxysterol levels were confirmed in murine NASH liver samples. Our results suggest increased bile acid synthesis in NASH samples, as judged by the enhanced level of 7 alpha-hydroxycholest-4-en-3-one and impaired 24S-hydroxycholesterol metabolism as characteristic biochemical changes in livers affected by NASH.}, language = {en} } @article{HechtMeierZimmeretal.2018, author = {Hecht, Markus and Meier, Friedegund and Zimmer, Lisa and Polat, B{\"u}lent and Loquai, Carmen and Weishaupt, Carsten and Forschner, Andrea and Gutzmer, Ralf and Utikal, Jochen S. and Goldinger, Simone M. and Geier, Michael and Hassel, Jessica C. and Balermpas, Panagiotis and Kiecker, Felix and Rauschenberg, Ricarda and Dietrich, Ursula and Clemens, Patrick and Berking, Carola and Grabenbauer, Gerhard and Schadendorf, Dirk and Grabbe, Stephan and Schuler, Gerold and Fietkau, Rainer and Distel, Luitpold V. and Heinzerling, Lucie}, title = {Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients}, series = {British Journal of Cancer}, volume = {118}, journal = {British Journal of Cancer}, doi = {10.1038/bjc.2017.489}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227970}, pages = {785-792}, year = {2018}, abstract = {Background: Concomitant radiation with BRAF inhibitor (BRAFi) therapy may increase radiation-induced side effects but also potentially improve tumour control in melanoma patients. Methods: A total of 155 patients with BRAF-mutated melanoma from 17 European skin cancer centres were retrospectively analysed. Out of these, 87 patients received concomitant radiotherapy and BRAFi (59 vemurafenib, 28 dabrafenib), while in 68 patients BRAFi therapy was interrupted during radiation (51 vemurafenib, 17 dabrafenib). Overall survival was calculated from the first radiation (OSRT) and from start of BRAFi therapy (OSBRAFi). Results: The median duration of BRAFi treatment interruption prior to radiotherapy was 4 days and lasted for 17 days. Median OSRT and OSBRAFi in the entire cohort were 9.8 and 12.6 months in the interrupted group and 7.3 and 11.5 months in the concomitant group (P=0.075/P=0.217), respectively. Interrupted vemurafenib treatment with a median OSRT and OSBRAFi of 10.1 and 13.1 months, respectively, was superior to concomitant vemurafenib treatment with a median OSRT and OSBRAFi of 6.6 and 10.9 months (P=0.004/P=0.067). Interrupted dabrafenib treatment with a median OSRT and OSBRAFi of 7.7 and 9.8 months, respectively, did not differ from concomitant dabrafenib treatment with a median OSRT and OSBRAFi of 9.9 and 11.6 months (P=0.132/P=0.404). Median local control of the irradiated area did not differ in the interrupted and concomitant BRAFi treatment groups (P=0.619). Skin toxicity of grade ≥2 (CTCAE) was significantly increased in patients with concomitant vemurafenib compared to the group with treatment interruption (P=0.002). Conclusions: Interruption of vemurafenib treatment during radiation was associated with better survival and less toxicity compared to concomitant treatment. Due to lower number of patients, the relevance of treatment interruption in dabrafenib treated patients should be further investigated. The results of this analysis indicate that treatment with the BRAFi vemurafenib should be interrupted during radiotherapy. Prospective studies are desperately needed.}, language = {en} } @article{EstesAnsteeAriasLosteetal.2018, author = {Estes, Chris and Anstee, Quentin M. and Arias-Loste, Maria Teresa and Bantel, Heike and Bellentani, Stefano and Caballeria, Joan and Colombo, Massimo and Craxi, Antonio and Crespo, Javier and Day, Christopher P. and Eguchi, Yuichiro and Geier, Andreas and Kondili, Loreta A. and Kroy, Daniela C. and Lazarus, Jeffrey V. and Loomba, Rohit and Manns, Michael P. and Marchesini, Giulio and Nakajima, Atsushi and Negro, Francesco and Petta, Salvatore and Ratziu, Vlad and Romero-Gomez, Manuel and Sanyal, Arun and Schattenberg, J{\"o}rn M. and Tacke, Frank and Tanaka, Junko and Trautwein, Christian and Wei, Lai and Zeuzem, Stefan and Ravazi, Homie}, title = {Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030}, series = {Journal of Hepatology}, volume = {69}, journal = {Journal of Hepatology}, doi = {10.1016/j.jhep.2018.05.036}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227286}, pages = {896-904}, year = {2018}, abstract = {Background \& Aims Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data. Methods A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections. Results If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30\%), between 2016-2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56\%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population. Conclusions NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden. Lay summary Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years.}, language = {en} }