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    Changes in hepatocellular carcinoma aggressiveness characteristics with an increase in tumor diameter
    (Sage Publications Ltd, 2021) Carr, Brian I.; Guerra, Vito; Donghia, Rossella; Farinati, Fabio; Giannini, Edoardo G.; Piscaglia, Fabio; Rapaccini, Gian Ludovico
    Background: Hepatocellular carcinoma prognosis depends on both liver and tumor determinants, especially on maximum tumor diameter, multifocality, and presence of portal vein thrombosis, despite apparently complete tumor removal by resection or liver transplantation. Aims: To examine parameters of hepatocellular carcinoma aggressiveness as tumor size increases. Methods: A large hepatocellular carcinoma database was examined for trends in serum alpha-fetoprotein and the percentage of patients with macroscopic portal vein thrombosis or tumor multifocality. Results: A total of 13,016 hepatocellular carcinoma patients were identified having full tumor and survival data. Of these, 76.56% were male and 23.44% were female, with a median age of 64.4 years. We found that as the maximum tumor diameter increased, there was a significant trend for increased alpha-fetoprotein levels (P<0.001) and an increased percentage of patients with either portal vein thrombosis or tumor multifocality, each P<0.0001. Furthermore, the increases of both alpha-fetoprotein and portal vein thrombosis were proportionately greater than the related maximum tumor diameter increases. These trends of increased alpha-fetoprotein, portal vein thrombosis, and multifocality with increasing maximum tumor diameter had non-linear patterns. Within alpha-fetoprotein and multifocality trends, there were identifiable sub-trends associated with specific maximum tumor diameter ranges. Conclusions: The greater fold-increases in alpha-fetoprotein and portal vein thrombosis compared with increases in maximum tumor diameter imply that hepatocellular carcinoma characteristics may change with increasing size to a more aggressive phenotype, suggesting that follow-up tumor sampling might be useful, in addition to baseline tumor sampling, for optimal therapeutic choices to be made.
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    Identification of Clinical Phenotypes and Related Survival in Patients with Large HCCs
    (Mdpi, 2021) Carr, Brian I.; Guerra, Vito; Donghia, Rossella; Farinati, Fabio; Giannini, Edoardo G.; Muratori, Luca; Rapaccini, Gian Ludovico
    Simple Summary Factors influencing the survival of hepatocellular carcinoma (HCC) patients include portal vein thrombosis (PVT), tumor numbers (multifocality), blood alpha-fetoprotein (AFP) levels, and the degree of liver damage (levels of blood bilirubin and albumin). However, the role of tumor size can be ambiguous. We therefore examined multiple clinical characteristics for their relationship with patient death and combined the three parameters with the greatest impact to create a tool to examine the characteristics and survival of patients with normal and abnormal levels of this three-parameter tool. In patients with large tumors, we found that normal levels of these three parameters-no PVT or multifocality plus normal blood albumin levels-were associated with longer survival than any group containing patients with PVT. This good-survival group could also be divided into two subgroups, differing in survival, based on blood AFP levels. This three-parameter tool might be prognostically useful in stratifying patients and management decisions. Background. Hepatocellular carcinoma (HCC) factors, especially maximum tumor diameter (MTD), tumor multifocality, portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP), influence survival. Aim. To examine patterns of tumor factors in large HCC patients. Methods. A database of large HCC patients was examined. Results. A multiple Cox proportional hazard model on death identified low serum albumin levels and the presence of PVT and multifocality, with each having a hazard ratio >= 2.0. All combinations of these three parameters were examined in relation to survival. Using univariate Cox analysis, the combination of albumin >3.5 g/dL and the absence of both PVT and multifocality had the best survival rate, while all combinations that included the presence of PVT had poor survival and hazard ratios. We identified four clinical phenotypes, each with a distinct median survival: patients with or without PVT or multifocality plus serum albumin >= 3.5 (g/dL), with each subgroup displaying high (>= 100 IU/mL) or low (<100 IU/mL) blood AFP levels. Across a range of MTDs, we identified only two significant trends, blood AFP and platelets. Conclusions. Patients with large HCCs have distinct phenotypes and survival, as identified by the combination of PVT, multifocality, and blood albumin levels.