24 research outputs found
Impact of Sarcopenia on the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib
Background and aims: Sarcopenia has been associated with poor outcomes in patients with cirrhosis and hepatocellular carcinoma. We investigated the impact of sarcopenia on survival in patients with advanced hepatocellular carcinoma treated with Sorafenib. Methods: A total of 328 patients were retrospectively analyzed. All patients had an abdominal CT scan within 8 weeks prior to the start of treatment. Two cohorts of patients were analyzed: the "Training Group" (215 patients) and the "Validation Group" (113 patients). Sarcopenia was defined by reduced skeletal muscle index, calculated from an L3 section CT image. Results: Sarcopenia was present in 48% of the training group and 50% of the validation group. At multivariate analysis, sarcopenia (HR: 1.47, p = 0.026 in training; HR 1.99, p = 0.033 in validation) and MELD > 9 (HR: 1.37, p = 0.037 in training; HR 1.78, p = 0.035 in validation) emerged as independent prognostic factors in both groups. We assembled a prognostic indicator named "SARCO-MELD" based on the two independent prognostic factors, creating three groups: group 1 (0 prognostic factors), group 2 (1 factor) and group 3 (2 factors), the latter with significantly worse survival and shorter time receiving treatment
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
Caractérisation clinique et moléculaire des hépato-cholangiocarcinomes
Contexte scientifique : Les cancers primitifs du foie incluent un large spectre de tumeurs, dont les carcinomes hépatocellulaires (CHC), les cholangiocarcinomes (CCA) et les hépato-cholangiocarcinomes (cHCC-CCA) qui comportent les deux contingents (CHC et CCA) au sein de la même lésion. En raison d'une hétérogénéité intra-tumorale importante, le diagnostic morphologique de cHCC-CCA est difficile. De plus, les études visant à évaluer son pronostic ont fourni des résultats discordants, avec un comportement tantôt proche du CHC, tantôt proche du CCA. De même, la prise en charge thérapeutique des cHCC-CCA n'est pas aussi bien codifiée que pour les CHC ou les CCA, le traitement préconisé pour les tumeurs résécables restant la chirurgie. Les chimiothérapies testées sont basées sur les molécules indiquées dans les CHC ou CCA, sans rationnel scientifique spécifique. Une prise en charge adaptée des patients avec cHCC-CCA repose donc sur une meilleure connaissance et caractérisation morphologique de ces tumeurs composites. Mon projet est articulé en deux projets cliniques (Projets 1 et 2) et un projet de recherche fondamentale (Projet 3). Projet 1, diagnostique : Nous avons démontré que la combinaison de caractéristiques morphologiques (macroscopiques via l'imagerie et histomoléculaires via la biopsie) est plus performante par rapport à chacune des modalités prises séparément. Toutefois, le développement de nouveaux marqueurs tissulaires permettrait d'améliorer son diagnostic pré-opératoire (cf projet 3). Projet 2, thérapeutique : Pour remédier au manque de preuves scientifiques concernant les traitements systémiques du CHC-CCA métastatique/non résécable, nous avons rapporté dans une cohorte nationale multicentrique que l'efficacité des inhibiteurs de la tyrosine kinase (TKI) ou de la chimiothérapie à base de platine était comparable. En outre, dans notre étude, le score ALBI (Albumine/bilirubine) prédisait la survie des patients atteints de cHCC-CCA. Grâce à une comparaison avec des cohortes de CHC et CCA métastatiques/non résécables appariés, traités par chimiothérapie, nous avons observé que la médiane de survie après traitements systémiques était superposable dans les trois types tumoraux (cHCC-CCA, CHC et CCA). Projet 3, analyse moléculaire : Afin d'obtenir une caractérisation moléculaire exhaustive du cHCC-CCA, nous avons utilisé une approche d'imagerie MALDI (spectrométrie de masse in situ), permettant l'obtention de profils moléculaires (peptidiques) à haute résolution spatiale directement à partir de coupes tissulaires fixées sans étape préalable de marquage. Nous avons, dans un premier temps, construit des tissues-microarrays (TMA) à partir d'une cohorte de cHCC-CCAs reséqués et comparé les profils peptidiques avec des CHC et CCA. Nous avons ainsi identifié un set de marqueurs moléculaires peptidiques spécifiques des cHCC-CCA. Le potentiel pronostique et théranostique de ces marqueurs a été également évalué. Dans un second temps, afin d'explorer de façon plus précise l'hétérogénéité intra-tumorale, nous avons analysé en MALDI des lames entières de cHCC-CCA reséqués. Les informations obtenues grâce aux techniques de protéomique ont été comparées aux images histologiques et immunophénotypiques. Cette analyse a permis d'identifier des zones tumorales supplémentaires non détectées par les techniques conventionnelles. Conclusions : En conclusion, les travaux présentés contribuent à améliorer le diagnostic des cHCC-CCA en combinant des approches d'imagerie conventionnelle et innovantes (imagerie MALDI). Grâce à une étude multicentrique française, nous avons évalué l'efficacité des thérapies systémiques dans les cHCC-CCA, en particulier des thérapies à base de platine et les TKI. Les perspectives de ce travail incluent le développement de marqueurs tissulaires applicables en routine clinique afin de guider non seulement le diagnostic mais aussi le choix thérapeutique.Scientific background: Primary liver cancers include a wide spectrum of tumors, featuring hepatocellular carcinomas (HCC), cholangiocarcinomas (CCA) and hepato-cholangiocarcinomas (cHCC-CCA) which have both contingents (HCC and CCA) merged in the same lesion. Due to significant intra-tumor heterogeneity, the morphological diagnosis of cHCC-CCA is difficult. In addition, studies aimed at evaluating its prognosis have provided discordant results, with behavior sometimes close to HCC, sometimes close to CCA. Similarly, the therapeutic management of cHCC-CCA is not as well codified as for HCC or CCA, the recommended treatment for resectable tumors remaining surgery. The chemotherapies used are based on the molecules indicated in the CHCs or CCAs, with no specific scientific rationale. Appropriate management of patients with cHCC-CCA is therefore based on better knowledge and morphological characterization of these composite tumors. My project is articulated in two clinical projects (Projects 1 and 2) and a fundamental research project (Project 3). Project 1, diagnostic: We have demonstrated that the combination of morphological characteristics (macroscopic, via imaging and histomolecular, via biopsy) is more efficient compared to each of the modalities taken separately. However, the development of new tissue markers would improve its preoperative diagnosis (see project 3). Project 2, Therapeutics: To address the lack of scientific evidence regarding systemic treatments for metastatic/unresectable HCC-CCA, we reported in a national multicenter cohort that the efficacy of tyrosine kinase inhibitors (TKIs) or chemotherapy platinum-based was comparable. In addition, in our study, the ALBI (Albumin/bilirubin) score predicted the survival of patients with cHCC-CCA. Through a comparison with matched cohorts of metastatic/unresectable HCC and CCA treated with chemotherapy, we observed that the median survival after systemic treatments was similar in the three tumor types (cHCC-CCA, HCC and CCA). Project 3, molecular analysis: In order to obtain an exhaustive molecular characterization of cHCC-CCA, we used an MALDI imaging approach (in situ mass spectrometry), allowing the obtaining of high resolution spatialized molecular profiles directly from fixed tissue sections without prior labeling step. We first constructed tissue-microarrays (TMA) from a cohort of resected cHCC-CCAs and compared the peptide profiles with CHCs and CCAs. We have thus identified a set of peptide markers specific for cHCC-CCA. The prognostic and theranostic potential of these markers was also evaluated. In a second step, in order to explore more precisely the intra-tumor heterogeneity, we analyzed in MALDI-MSI whole slides of resected cHCC-CCA. Information obtained through proteomic techniques was compared to histological and immunophenotypic images. This analysis made it possible to identify additional tumor areas not detected by conventional techniques. Conclusions: In conclusion, the work presented contributes to improving the diagnosis of cHCC-CCA by combining conventional and innovative imaging approaches (MALDI imaging). Thanks to a French multi-centric study, we evaluated the efficacy of systemic therapies in cHCC-CCA, in particular platinum-based therapies and TKIs. The perspectives of this work include the development of tissue markers applicable in clinical routine in order to guide not only the diagnosis but also the therapeutic choice
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
Hepatocellular carcinoma in the context of non-alcoholic steatohepatitis (NASH): recent advances in the pathogenic mechanisms
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