Advances and Insights into Neurological Practice 2016-17

Papers published by the European Journal of Neurology reflect the broad interest of practicing neurologists in advances in the aetiology, diagnosis and management of neurological disorders. As a general journal, the proportion of papers in the different subject areas reasonably reflects the case load of a practising neurologist. Stroke represents the largest proportion of papers published, including those on pathophysiology (1-23), acute stroke management (24-47) and the outcome of patients who have suffered stroke (48-72). This article is protected by copyright. All rights reserved

Hepatocellular carcinoma on the background of nonalcoholic fatty liver disease: epidemiological update

The epidemiological features of hepatocellular carcinoma have changed significantly in the last decades. While for a long-time viral hepatitis and alcohol consumption have been the leading risk factors, the current spread of obesity and type 2 diabetes has contributed to the emergence of non-alcoholic fatty liver disease (NAFLD) worldwide, which has become the leading chronic liver disease as well as one of the main etiologies of hepatocellular carcinoma (HCC), especially in western countries. In this review, we resume the latest data about the epidemiology of metabolic liver disease and HCC arising from NAFLD and discuss the main clinical and molecular features leading to the progression of liver disease and the development of HCC in NAFLD. The emerging concept of metabolic associated fatty liver disease and its association with the development of HCC are also introduced

Hepatocellular carcinoma in the context of non-alcoholic steatohepatitis (NASH): recent advances in the pathogenic mechanisms

International audienceHepatocellular carcinoma (HCC) is the most common type of liver cancer. HCC is particularly aggressive and is one of the leading causes of cancer mortality. In recent decades, the epidemiological landscape of HCC has undergone significant changes. While chronic viral hepatitis and excessive alcohol consumption have long been identified as the main risk factors for HCC, non-alcoholic steatohepatitis (NASH), paralleling the worldwide epidemic of obesity and type 2 diabetes, has become a growing cause of HCC in the US and Europe. Here, we review the recent advances in epidemiological, genetic, epigenetic and pathogenic mechanisms as well as experimental mouse models that have improved the understanding of NASH progression toward HCC. We also discuss the clinical management of patients with NASH-related HCC and possible therapeutic approaches

MALDI Imaging, a Powerful Multiplex Approach to Decipher Intratumoral Heterogeneity: Combined Hepato-Cholangiocarcinomas as Proof of Concept

Combined hepato-cholangiocarcinomas (cHCC-CCA) belong to the spectrum of primary liver carcinomas, which include hepatocellular carcinomas (HCC) and intrahepatic cholangiocarcinomas (iCCA) at both ends of the spectrum. Mainly due to the high intratumor heterogeneity of cHCC-CCA, its diagnosis and pathological description remain challenging. Taking advantage of in situ non-targeted molecular mapping provided by MALDI (Matrix Assisted Laser Desorption Ionization) imaging, we sought to develop a multiscale and multiparametric morphological approach, integrating molecular and conventional pathological analysis. MALDI imaging was applied to five representative cases of resected cHCC-CCA. Principal component analysis and segmentations with MALDI imaging techniques identified areas related to either iCCA or HCC and also hidden tumor areas not visible microscopically. In addition, the overlap between MALDI segmentation and immunostaining provided a comprehensive description of cHCC-CCA tumor heterogeneity by identifying transitional and micro-metastatic areas. Moreover, a list of peptides derived from in silico digestion was obtained for each immunohistochemical marker and was matched within the peptide peak list acquired by MALDI. Comparison of immunostaining images with ions from in silico digestion revealed an accurate identification of iCCA and HCC areas. Our study provides further evidence on the performance of MALDI imaging in exploring intratumor heterogeneity and offering virtual multiplex immunostaining through a single acquisition

Sarcopenia predicts reduced survival in patients with hepatocellular carcinoma at first diagnosis.

Abstract: Background. Sarcopenia is a complication and independent risk factor for mortality in patients with liver cirrhosis. Aim. To assess the prevalence and influence of sarcopenia on overall survival in a cohort of cirrhotic patients with hepatocellular carcinoma managed in a tertiary center. Material and methods. Abdominal computed tomography of 92 consecutive hepatocellular carcinoma cirrhotic patients, enrolled and followed from 2004 to 2014, were retrospectively studied with a software analyzing the cross-sectional areas of muscles at third lumbar vertebra level. Data was normalized for height, skeletal muscle index (SMI) calculated and presence of Sarcopenia measured. Sarcopenia was defined by SMI ≤ 41 cm2/m2 for women and ≤ 53 cm2/m2 for men with body mass index (BMI) ≥ 25, and ≤ 43 cm2/m2 for men and women with BMI < 25, respectively. Results. Median age at diagnosis was 71.9 years (30.7-86.4) and BMI 24.7 (17.5-36.7), comparable in women 23.1, (17.5-36.7) and men 24.7 (18.4-36.7). A class of CHILD score and BCLC A prevailed (55.4% and 41.3%, respectively); metastatic disease was found in 12% of cases. Sarcopenia was present in 40.2% of cases, mostly in females (62.9%; p = 0.005). Mean overall survival was reduced in sarcopenic patients, 66 (95% CI 47 to 84) vs. 123 (95% CI 98 to 150) weeks (p = 0.001). At multivariate analysis, sarcopenia was a predictor of reduced overall survival, independent of age (p = 0.0027). Conclusions. This retrospective study shows high prevalence of sarcopenia among cirrhotic patients with hepatocellular carcinoma. Presence of sarcopenia was identified as independent predictor of reduced overall survival. As easily measurable by CT, sarcopenia should be determined for prognostic purposes in this patient population