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Guerra V.,National Institute for Digestive Diseases
European Journal of Gastroenterology and Hepatology | Year: 2014

Background: Massive hepatocellular carcinomas (HCCs) are uncommon and poorly characterized. Aim: To characterize a large cohort of HCC patients with massive tumors, with documented baseline characteristics and survival data. Methods: Records were examined of a cohort of 344 biopsy-proven and randomly presenting unresectable HCC patients with tumors of at least 10 cm diameter (massive), which were analyzed for their clinical characteristics and survival. Results: Massive HCC patients were significantly different from others, in having less severe cirrhosis and higher blood platelet counts, α-fetoprotein (AFP), alkaline phosphatase (ALKP), and γ-glutamyl transpeptidase (GGTP) levels. Platelets, ALKP, and GGTP correlated with tumor size. Within massive HCCs, ALKP levels related to tumor number, whereas platelet counts related to tumor size. AFP and GGTP related to neither. All four parameters related to survival. A multivariate Cox proportional hazard model showed that ALKP and AFP were significant for overall survival. Survival of massive tumors was not significantly worse than for other larger tumors. Conclusion: Massive HCCs were characterized by high blood platelets, AFP, ALKP, and GGTP levels. AFP levels were important for survival, but did not directly relate to tumor size or number, suggesting that AFP represents some other property of massive HCC biology. Patients with massive HCC should thus be considered for active therapeutic intervention, just as for other sizes of HCC. Copyright ©2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Carr B.I.,National Institute for Digestive Diseases | Carr B.I.,Thomas Jefferson University
Seminars in Oncology | Year: 2012

A concordance of multiple advances is changing the management of hepatocellular carcinoma (HCC). These include: (1) identification of preventable and treatable causal factors, including hepatitis B and obesity (non-alcoholic steatotic hepatitis [NASH]); (2) description of molecular and proteomic profiles for HCC prognosis, disease subtyping, and drug selection; (3) identification of circulating tumor cells for non-invasive molecular typing; (4) identification of tumor stem cells, for HCC subtyping and as treatment targets; (5) large numbers of multi-kinase inhibitors that are currently undergoing clinical trial assessment and comparison; (6) an array of newer therapies of different drug classes, aimed at a wide range of targets in cell growth, apoptosis, autophagy, and tumor invasion pathways; (7) newer regional chemotherapy and radiotherapy regimens and delivery systems; (8) the extension of liver transplantation to larger HCCs and its wider availability through use of living-related organ donors; (9) new radiological techniques to assess the changes in HCC vascularity associated with angiogenic drug actions; (10) re-evaluation of the importance of tumor biopsy to obtain molecular signatures; (11) recognition of the importance of non-tumor liver parenchyma for tumor growth control and as a source of prognostic profiling in HCC patients; (12) the evaluation of kinase- and other inhibitors in neo-adjuvant and adjuvant therapy associated with resection and liver transplant and minimization of transplant waiting list drop-out; (13) re-evaluation of the role or limitation of tumor responses, since kinase inhibitors can enhance survival without HCC size responses; and (14) the development of combination therapies to enhance tumor control rates, either using drugs targeting differing pathways, or kinase-inhibitors combined with either chemotherapy drugs or yttrium 90. © 2012 Elsevier Inc. Source

Bonamassa B.,Laboratory of Lipid Metabolism and Cancer | Moschetta A.,Laboratory of Lipid Metabolism and Cancer | Moschetta A.,University of Bari | Moschetta A.,Italian National Cancer Institute | Moschetta A.,National Institute for Digestive Diseases
Trends in Endocrinology and Metabolism | Year: 2013

Modulation of the cholesterol-sensing liver X receptors (LXRs) and their downstream targets has emerged as promising therapeutic avenues in atherosclerosis. The intestine is important for its unique capabilities to act as a gatekeeper for cholesterol absorption and to participate in the process of cholesterol elimination in the feces and reverse cholesterol transport (RCT). Pharmacological and genetic intestine-specific LXR activation have been shown to protect against atherosclerosis. In this review we discuss the LXR-targeted molecular players in the enterocytes as well as the intestine-driven pathways contributing to cholesterol homeostasis with therapeutic potential as targets in the prevention and treatment of atherosclerosis. © 2012 Elsevier Ltd. Source

Orlando A.,National Institute for Digestive Diseases | Russo F.,National Institute for Digestive Diseases
Journal of Gastrointestinal Cancer | Year: 2013

Introduction Cancers of the gastrointestinal tract account for 25 % of all cancers and for 9 % of all causes of cancer death in the world, so gastrointestinal cancers represent a major health problem. In the past decades, an emerging role has been attributed to the interactions between the gastrointestinal content and the onset of neoplasia. Methods Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. Probiotics are mono or mixed cultures of live microorganisms that might beneficially affect the host by improving the characteristics of indigenous microflora. Although the effects of probiotic administration has been intensively investigated in vitro, in animal models, in healthy volunteers, and in some human gastrointestinal diseases, very little is still known about the possible cross-interactions among probiotic administration, changes of intestinal flora, and the neoplastic transformation of gastrointestinal mucosa. Results Theoretically, probiotics are able to reduce cancer risk by a number of mechanisms: (a) binding and degradation of potential carcinogens; (b) quantitative, qualitative and metabolic alterations of the intestinal microflora; (c) production of anti-tumorigenic or anti-mutagenic compounds; (d) competitive action towards pathogenic bacteria; (e) enhancement of the host's immune response; (f) direct effects on cell proliferation. Conclusion This review will attempt to highlight the literature on the most widely recognized effects of probiotics against neoplastic transformation of gastrointestinal mucosa and in particular on their effects on cell proliferation. © Springer Science+Business Media New York 2012. Source

Pancoska P.,University of Pittsburgh | Carr B.I.,National Institute for Digestive Diseases
Seminars in Oncology | Year: 2014

We previously developed a network phenotyping strategy (NPS), a graph theory-based transformation of clinical practice data, for recognition of two primary subgroups of hepatocellular cancer (HCC), called S and L, which differed significantly in their tumor masses. In the current study, we have independently validated this result on 641 HCC patients from another continent. We identified the same HCC subgroups with mean tumor masses 9 cm x n (S) and 22 cm x n (L), P<10-14. The means of survival distribution (not available previously) for this new cohort were also significantly different (S was 12 months, L was 7 months, P<10-5). We characterized nine unique reference patterns of interactions between tumor and clinical environment factors, identifying four subtypes for S and five subtypes for L phenotypes, respectively. In L phenotype, all reference patterns were portal vein thrombosis (PVT)-positive, all platelet/alpha fetoprotein (AFP) levels were high, and all were chronic alcohol consumers. L had phenotype landmarks with worst survival. S phenotype interaction patterns were PVT-negative, with low platelet/AFP levels. We demonstrated that tumor-clinical environment interaction patterns explained how a given parameter level can have a different significance within a different overall context. Thus, baseline bilirubin is low in S1 and S 4, but high in S2 and S3, yet all are S subtype patterns, with better prognosis than in L. Gender and age, representing macro-environmental factors, and bilirubin, prothrombin time, and AST levels representing micro-environmental factors, had a major impact on subtype characterization. Clinically important HCC phenotypes are therefore represented by complete parameter relationship patterns and cannot be replaced by individual parameter levels. © 2014 Elsevier Inc. Source

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