1,721,010 research outputs found
Protein Biomarkers in the Management of Hepatocellular Carcinoma: Novel Combinatory Approaches
No full textSeveral serum biomarkers have been proposed for diagnosis and assessment of prognosis in hepatocellular carcinoma (HCC) but none has entered routine clinical practice despite achieving reasonably high values for sensitivity, specificity and area under the ROC curve. After reviewing some of these we show how the performance of individual biomarkers may be enhanced by combining several different biomarkers in rigorously developed and validated statistical models. In such models the constituent biomarkers are considered as continuous variables rather than, as in conventional clinical practice, dichotomised with the application of cut-off points. This approach maximises the information extracted from the available data. We illustrate this concept with reference to the ‘GALAD’ model for diagnosis and the ‘BALAD’ model for prognosis both of which improve the utility of the individual constituent biomarkers
Plasma cholesterol and lipoprotein levels in relation to tumor aggressiveness and survival in HCC patients
No full textAbstract
Background and Aims: Hepatocellular carcinoma is associated with several chronic liver diseases, especially chronic hepatitis B virus, hepatitis C virus, and alcoholism. It is increasingly appreciated that obesity/metabolic syndrome is also associated with chronic liver disease and subsequent hepatocellular carcinoma. Methods: We retrospectively investigated the serum lipid profiles in a large hepatocellular carcinoma cohort, associated predominantly with the hepatitis B virus, hepatitis C virus, alcohol or nonalcoholic steatohepatitis. The cohort was examined both as a whole, as well as stratified by etiology. Results: We found significant associations between parameters of hepatocellular carcinoma biology such as maximum tumor diameter, portal vein thrombosis, tumor multifocality or alpha-fetoprotein levels and individual lipid components, including total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and body mass index. In a final multiple linear regression model considering all lipid variables together, only high-density lipoprotein cholesterol was significantly associated with the tumor Tumor Aggressiveness Index. High-density lipoprotein cholesterol was found to have a statistically higher hazard ratio for death than low high-density lipoprotein cholesterol levels (Cox). On examination by etiological group, alpha-fetoprotein levels were significantly higher in patients with hepatitis C virus compared to those with alcohol or nonalcoholic steatohepatitis, but maximum tumor diameter, tumor multifocality and portal vein thrombosis were similar across etiological groups. Nonalcoholic steatohepatitis patients had significantly less cirrhosis than other groups and hepatitis B virus patients had significantly higher cholesterol and low-density lipoprotein cholesterol levels than hepatitis C virus patients. Conclusions: This is the first report, to our knowledge, of a relationship between serum lipid parameters and indices of hepatocellular carcinoma growth, invasion and aggressiveness, as well as with survival
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
MEK 1/2 inhibitors in the treatment of hepatocellular carcinoma
No full textSorafenib is the only approved systemic treatment for advanced hepatocellular carcinoma patients and all the recently published randomized controlled trials on new systemic drugs have been unsuccessful. This is likely due to a lack of understanding of tumor progression, molecular drivers, and liver toxicity, as well as flaws in trial design. An important signaling pathway in hepatocarcinogenesis is the MEK cascade involved in various cellular responses, including adaptation and survival. A key role in this cascade is played by MEK, of which MEK 1/2 represent the prototypes and an interesting target for new oncological drugs. This review analyzes recent developments and future perspectives on the role of MEK inhibitors in hepatocellular carcinoma treatment
Serum ferritin as a new prognostic factor in hepatocellular carcinoma patients treated with radiofrequency ablation
No full textBackground and Aim: Hepatic iron accumulation is considered to be a cofactor that
influences liver injury and hepatocarcinogenesis. Aim of this study is to determine whether
serum ferritin (SF) levels relate to overall survival (OS) and time to recurrence (TTR) in
hepatocellular carcinoma (HCC) patients treated with percutaneous radiofrequency ablation
(RFA).
Methods: We measured SF levels in 103 HCC patients (median age 70, M/F = 82.5%/
17.5%) who underwent RFA between 2005 and 2010. Correlation between SF and other
prognostic factors at baseline was analyzed. SF levels were entered into a Cox model and
their influence on OS and TTR was evaluated in univariate and multivariate analyses.
Results: SF did not correlate with α-fetoprotein (rho: −0.12, P = 0.22), neutrophil/
lymphocyte ratio (rho: −0.1020, P = 0.30), Model for End-Stage Liver Disease (rho: 0.18,
P = 0.06), Child-Pugh score (P = 0.5), or Barcelona Cancer of the Liver Clinic stage
(P = 0.16). A log-rank test found the value of 244 ng/mL as the optimal prognostic cut-off
point for SF. Median OS was 62 months (54–78) and survival rate was 97%, 65%, and 52%
at 1, 4, and 5 years, respectively. Performance status and SF were the only predictors of OS
at multivariate analysis. Median TTR was 38 months (34–49) with a recurrence-free
survival rate of 82.5%, 26.2%, and 23.3% at 1, 4, and 5 years, respectively, while SF and
age were the only predictors of TTR.
Conclusions: SF level, possibly reflecting the degree of hepatic inflammation and fibrosis,
is a negative risk factor for survival and recurrence after percutaneous RFA in HCC
patients
Angiotensin receptor blockers improve survival outcomes after radiofrequency ablation in hepatocarcinoma patients
No full textBackground and Aim: Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking. The aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation.
Methods: Data on 153 patients were reviewed. The study population was classified into three groups: 73 (47.8%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 49 (32%) patients treated with angiotensin-converting enzyme inhibitors (group 2), and 31 (20.2%) patients treated with sartans (group 3). Survival outcomes were analysed by means of Kaplan-Meier analysis and compared with log-rank test.
Results: In the whole study population, 85.6% of patients were in Child-Pugh A class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30mm (10-40) and alpha fetoprotein was 25 (1.1-2100) UI/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (95% confidence interval: 31-58) in group 1, 72 months (49-89) in group 2, and 84 months (58-92) in group 3 (P=0.02). Median time to recurrence was 26 (15-42), 44 (33-72), and 69 (44-74) months in the three groups, respectively (P=0.02). Sartan therapy was a significant predictor of longer overall survival and delayed time to recurrence on multivariate analysis. Conclusion: Sartans significantly improved overall survival and time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients
Angiotensin receptor blockers improve survival outcomes after radiofrequency ablation in hepatocarcinoma patients
No full textBackground and Aim: Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking. The aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation.
Methods: Data on 153 patients were reviewed. The study population was classified into three groups: 73 (47.8%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 49 (32%) patients treated with angiotensin-converting enzyme inhibitors (group 2), and 31 (20.2%) patients treated with sartans (group 3). Survival outcomes were analysed by means of Kaplan-Meier analysis and compared with log-rank test.
Results: In the whole study population, 85.6% of patients were in Child-Pugh A class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30mm (10-40) and alpha fetoprotein was 25 (1.1-2100) UI/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (95% confidence interval: 31-58) in group 1, 72 months (49-89) in group 2, and 84 months (58-92) in group 3 (P=0.02). Median time to recurrence was 26 (15-42), 44 (33-72), and 69 (44-74) months in the three groups, respectively (P=0.02). Sartan therapy was a significant predictor of longer overall survival and delayed time to recurrence on multivariate analysis. Conclusion: Sartans significantly improved overall survival and time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients
Serum ferritin as a new prognostic factor in hepatocellular carcinoma patients treated with radiofrequency ablation
No full textBackground and Aim: Hepatic iron accumulation is considered to be a cofactor that
influences liver injury and hepatocarcinogenesis. Aim of this study is to determine whether
serum ferritin (SF) levels relate to overall survival (OS) and time to recurrence (TTR) in
hepatocellular carcinoma (HCC) patients treated with percutaneous radiofrequency ablation
(RFA).
Methods: We measured SF levels in 103 HCC patients (median age 70, M/F = 82.5%/
17.5%) who underwent RFA between 2005 and 2010. Correlation between SF and other
prognostic factors at baseline was analyzed. SF levels were entered into a Cox model and
their influence on OS and TTR was evaluated in univariate and multivariate analyses.
Results: SF did not correlate with α-fetoprotein (rho: −0.12, P = 0.22), neutrophil/
lymphocyte ratio (rho: −0.1020, P = 0.30), Model for End-Stage Liver Disease (rho: 0.18,
P = 0.06), Child-Pugh score (P = 0.5), or Barcelona Cancer of the Liver Clinic stage
(P = 0.16). A log-rank test found the value of 244 ng/mL as the optimal prognostic cut-off
point for SF. Median OS was 62 months (54–78) and survival rate was 97%, 65%, and 52%
at 1, 4, and 5 years, respectively. Performance status and SF were the only predictors of OS
at multivariate analysis. Median TTR was 38 months (34–49) with a recurrence-free
survival rate of 82.5%, 26.2%, and 23.3% at 1, 4, and 5 years, respectively, while SF and
age were the only predictors of TTR.
Conclusions: SF level, possibly reflecting the degree of hepatic inflammation and fibrosis,
is a negative risk factor for survival and recurrence after percutaneous RFA in HCC
patients
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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