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Öğe 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 LudovicoBackground: 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.Öğe 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 LudovicoSimple 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.Öğe Microscopic Portal Vein Invasion in Relation to Tumor Focality and Dimension in Patients with Hepatocellular Carcinoma(Springer, 2022) Carr, Brian, I; Guerra, Vito; Donghia, Rossella; Ince, Volkan; Akbulut, Sami; Ersan, Veysel; Usta, SertacBackground Microscopic portal vein invasion (microPVI) and tumor multifocality are hepatocellular carcinoma (HCC) prognosis factors. To investigate whether microPVI and multifocality are directly related to each other. Methods We retrospectively analyzed the relationships between microPVI, multifocality, and maximum tumor diameter (MTD) in prospectively collected transplanted HCC patients. Results HCCs with 1, 2, or >= 3 foci had more microPVI in larger than in smaller HCCs, with microPVI being present in 52.24% of single large foci. Conversely, microPVI patients had similar percentages of single and multifocal lesions. A linear regression model of MTD, showed microPVI best associated with MTD, with 2.49 as coefficient, whereas multifocality had a 0.83 coefficient. A logistic regression model of microPVI showed significant association with tumor multifocality, especially for small HCCs. Trends for microPVI and multifocality in relation to MTD revealed that both increased with MTD but more significantly for microPVI. Survival was similar in patients with small HCCs, with or without microPVI, but was significantly worse in microPVI patients with larger HCCs. No patient survival differences were found in relation to focality. Conclusions MTD had stronger associations with microPVI than with multifocality. microPVI was associated with worse survival in patients with large HCCs, but survival was not impacted by number of tumor foci. microPVI and multifocality appear weakly related, having different behavior in relation to MTD and survival.Öğe Relationships Between Indices of Tumor Aggressiveness in Hepatocellular Carcinoma(Springer, 2021) Carr, Brian I.; Guerra, Vito; Donghia, Rossella; Yilmaz, SeaiBackground Hepatocellular carcinoma (HCC) aggressiveness factors include serum levels of alpha-fetoprotein (AFP), maximum tumor diameter (MTD), tumor multifocality, and presence of portal vein thrombosis (PVT). Aims The interdependence of these factors has not been closely studied. Methods A large HCC database was examined for the presence of patients with PVT and multifocality and was analyzed retrospectively for the relationship of these 2 parameters to each other and to MTD and survival. Results Multifocality was found to increase with increase in MTD in the whole cohort and especially in patients with PVT. PVT also increased with increasing MTD. Neither increases in multifocality nor in PVT depended on elevated serum AFP levels, although they each increased with higher AFP levels. PVT increased in monofocal tumors as MTD increased but increased further in multifocal tumors. Conclusions Multifocality and PVT appear to be separate processes, each increasing with increase in MTD and AFP levels. The data support the hypothesis that in hepatocarcinogenesis, various factors cause increase in MTD, that in turn causes increased multifocality and PVT, which are non-co-dependent. However, both multifocality and PVT mechanisms involve both HCC cell growth and invasiveness, multifocality in liver parenchyma, and PVT in the portal vein.
