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Dimensions of hepatocellular carcinoma phenotypic diversity

World Journal of Gastroenterology 2018年第40期24卷 4536-4547页

作者： Romain Désert Natalia Nieto Orlando Musso institut numecan Université de Rennes 1 Institut national de la recherche agronomique (INRA) Institut national de la santé et de la recherche médicale (INSERM) Department of Pathology Department of Medicine (Gastroenterology and Hepatology) University of Illinois at Chicago

Hepatocellular carcinoma(HCC) is the 3^(rd) leading cause of cancer-related death worldwide. More than 80% of HCCs arise within chronic liver disease resulting from viral hepatitis, alcohol, hemochromatosis, obesity and metabolic syndrome or genotoxins. Projections based on Western lifestyle and its metabolic consequences anticipate a further increase in incidence, despite recent breakthroughs in the management of viral hepatitis. HCCs display high heterogeneity of molecular phenotypes, which challenges clinical management. However, emerging molecular classifications of HCCs have not yet formed a unified corpus translatable to the clinical practice. Thus, patient management is currently based upon tumor number, size, vascular invasion, performance status and functional liver reserve. Nonetheless, an impressive body of molecular evidence emerged within the last 20 years and is becoming increasingly available to medical practitioners and researchers in the form of repositories. Therefore, the aim this work is to review molecular data underlying HCC classifications and to organize this corpus into the major dimensions explaining HCC phenotypic diversity. Major efforts have been recently made worldwide toward a unifying "clinically-friendly" molecular landscape. As a result, a consensus emerges on three major dimensions explaining the HCC heterogeneity. In the first dimension, tumor cell proliferation and differentiation enabled allocation of HCCs to two major classes presenting profoundly different clinical aggressiveness. In the second dimension, HCC microenvironment and tumor immunity underlie recent therapeutic breakthroughs prolonging patients' survival. In the third dimension,metabolic reprogramming, with the recent emergence of subclass-specific metabolic profiles, may lead to adaptive and combined therapeutic approaches. Therefore, here we review recent molecular evidence, their impact on tumor histopathological features and clinical behavior and highlight the r

关键词： Liver metabolism Liver zonation Hepatocellular carcinoma classification Wnt/β-catenin TP53 Tumor microenvironment Inflammation Tumor immunity Hepatocyte proliferation Hepatocyte differentiation

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Combined evaluation of biomarkers as predictor of maintained remission in Crohn's disease

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World Journal of Gastroenterology 2019年第19期25卷 2354-2364页

作者： Elisa Sollelis Régine Minet Quinard Guillaume Bouguen Marion Goutte Félix Goutorbe Damien Bouvier Bruno Pereira Gilles Bommelaer Anthony Buisson Inserm 3i HP CHU Clermont-Ferrand Service d’Hépato-Gastro Entérologie Université Clermont Auvergne Inserm U1071 M2i SH USC-INRA 2018 Université Clermont Auvergne Biochemistry laboratory University Hospital G.Montpied CHU Rennes Univ Rennes INSERM CIC1414 Institut NUMECAN (Nutrition Metabolisms and Cancer) Gastroenterology Department Hospital of Bayonne Biostatistics Unit DRCI University Hospital

BACKGROUND The individual performances and the complementarity of Crohn's disease(CD)activity index(CDAI), C-reactive protein(CRP) and faecal calprotectin(Fcal) to monitor patients with CD remain poorly inves-tigated in the era of "tight control"and "treat to target" *** To assess CDAI, CRP and Fcal variation, alone or combined, after 12 wk(W12) of anti-tumor necrosis factor(TNF) therapy to predict corticosteroids-free remission(CFREM = CDAI 150 and either CRP >2.9 mg/L or Fcal > 250 μg/g were prospectively *** Among the 40 included patients, 13 patients(32.5%) achieved CFREM at W52. In univariable analysis, CDAI < 150 at W12(P = 0.012), CRP level < 2.9 mg/L at W12(P = 0.001) and Fcal improvement at W12(Fcal < 300 μg/g; or, for patients with initial Fcal < 300 μg/g, at least 50% decrease of Fcal or normalization of Fcal(< 100 μg/g)(P = 0.001) were predictive of CFREM at W52. Combined endpoint(CDAI < 150 and CRP ≤ 2.9 mg/L and FCal improvement) at W12 was the best predictor of CFREM at W52 with positive predictive value = 100.0%(100.0-100.0)and negative predictive value = 87.1%(75.3-98.9). In multivariable analysis, Fcal improvement at W12 [odd ratio(OR) = 45.1(2.96-687.9); P = 0.03] was a better predictor of CFREM at W52 than CDAI < 150 [OR = 9.3(0.36-237.1); P = 0.145]and CRP < 2.9 mg/L(0.77-278.0; P = 0.073).CONCLUSION The combined monitoring of CDAI, CRP and Fcal after anti-TNF induction therapy is able to predict favorable outcome within one year in patients with CD.

关键词： Biomarkers Crohn's disease Faecal calprotectin Crohn's disease activity index C-reactive protein Tight control Anti-tumor necrosis factor

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