Early onset of hypertension and serum electrolyte changes as potential predictive factors of activity in advanced hcc patients treated with sorafenib: results from a retrospective analysis of the HCC-AVR group

Hypertension (HTN) is frequently associated with the use of angiogenesis inhibitors targeting the vascular endothelial growth factor pathway and appears to be a generalized effect of this class of agent. We investigated the phenomenon in 61 patients with advanced hepatocellular carcinoma (HCC) receiving sorafenib. Blood pressure and plasma electrolytes were measured on days 1 and 15 of the treatment. Patients with sorafenib-induced HTN had a better outcome than those without HTN (disease control rate: 63.4% vs. 17.2% (p=0.001); progression-free survival 6.0 months (95% CI 3.2-10.1) vs. 2.5 months (95% CI 1.9-2.6) (p<0.001) and overall survival 14.6 months (95% CI9.7-19.0) vs. 3.9 months (95% CI 3.1-8.7) (p=0.003). Sodium levels were generally higher on day 15 than at baseline (+2.38, p<0.0001) in the group of responders (+4.95, p <0.0001) compared to patients who progressed (PD) (+0.28, p=0.607). In contrast, potassium was lower on day 14 (-0.30, p=0.0008) in the responder group (-0.58, p=0.003) than in those with progressive disease (-0.06, p=0.500). The early onset of hypertension is associated with improved clinical outcome in HCC patients treated with sorafenib. Our data are suggestive of an activation of the renin-angiotensin system in patients with advanced disease who developed HTN during sorafenib treatmen

Ten years of sorafenib in hepatocellular carcinoma: Are there any predictive and/or prognostic markers?

Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) since 2007 and numerous studies have investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC

Systematic versus on-demand early palliative care: A randomised clinical trial assessing quality of care and treatment aggressiveness near the end of life

Aim Early palliative care (EPC) in oncology has shown sparse evidence of a positive impact on patient outcomes, quality of care outcomes&nbsp;and costs. Patients and methods Data for this secondary analysis were taken from a trial of 207 outpatients with metastatic pancreatic cancer randomly assigned to receive standard cancer care plus on-demand EPC (standard arm) or standard cancer care plus systematic EPC (interventional arm). After 20 months\u2019 follow-up, 149 (80%) had died. Outcome measures were frequency, type and timing of chemotherapy administration, use of resources, place of death and overall survival. Results Some indices of end-of-life (EoL) aggressiveness had a favourable impact from systematic EPC. Interventional arm patients showed higher use of hospice services: a significantly longer median and mean period of hospice care (P&nbsp;=&nbsp;0.025 for both indexes) and a significantly higher median and mean number of hospice admissions (both P&nbsp;&lt;&nbsp;0.010). In the experimental arm, chemotherapy was performed in the last 30 days of life in a significantly inferior rate with respect to control arm: 18.7% versus&nbsp;27.8% (adjusted P&nbsp;=&nbsp;0.036). Other non-significant differences were seen in favour of experimental arm. Conclusions Systematic EPC showed a significant impact on some indicators of EoL treatment aggressiveness. These data, reinforced by multiple non-significant differences in most of the other items, suggest that quality of care is improved by this approach. This study is registered on ClinicalTrials.gov (NCT01996540)

Relationship between spatial ability, visuospatial working memory and self-assessed spatial orientation ability: a study in older adults

This paper describes some novel spatial tasks and questionnaires designed to assess spatial and orientation abilities. The new tasks and questionnaires were administered to a sample of 90 older adults (41 males, age range 57–90), along with some other tests of spatial ability (Minnesota Paper Form Board, Mental Rotations Test, and Embedded Figures Test) and tests of visuospatial working memory (Corsi’s Block Test and Visual Pattern Test). The internal reliability of the new tasks and questionnaires was analyzed, as well as their relationship with the spatial and working memory tests. The results showed that the new spatial tasks are reliable, correlate with working memory and spatial ability tests and, compared with the latters, show stronger correlations with the self-report questionnaires referring to orientation abilities. A model was also tested (with reference to Allen et al. in Intelligence 22:327–355, 1996) in which the new tasks were assumed to relate to spatial ability and predict orientation abilities as assessed by the self-report measures

External Powers in Latin America

This book examines the role of external powers in Latin America in the 21st century. Non-traditional partners have significantly increased their political and economic engagement with the continent. Five key questions arise: why has this surge taken place; when has it happened; in which regions and sectors is it mostly felt; what is the Latin American perspective; and what are the actual results? The book analyses 16 case studies: the United States, the European Union, China, Russia, Japan, Canada, India, Turkey, Iran, Israel, South Korea, Taiwan, Indonesia, the ASEAN countries, South Africa and Australia. The spectrum of existing explanations in the literature spans from neo-extractivism to South-South cooperation. This volume places them in context and proposes a more multifaceted approach, stressing a combination of systemic factors and internal dynamics both in Latin America and in the external partner countries. Geopolitics still matters and so do nation states, their interests and leaders. Ultimately, this surge in engagement has largely reproduced past patterns. Are new partners that different from the old ones

Radioembolization versus chemoembolization for unresectable hepatocellular carcinoma: a meta-analysis of randomized trials

Andrea Casadei Gardini,1,* Emiliano Tamburini,2,* Mercedes I&ntilde;arrairaegui,3 Giovanni Luca Frassineti,1 Bruno Sangro3 1Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 2Department of Medical Oncology, Ospedale Infermi, Rimini, Italy; 3Liver Unit, Cl&iacute;nica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain *These authors contributed equally to this work Purpose: This study aimed to compare clinically relevant outcomes following transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) in patients with unresectable hepatocellular carcinoma (HCC) using only prospective randomized clinical trials as a source of information.Materials and methods: A meta-analysis was performed to compare the efficacy of TARE and TACE in treating patients with unresectable HCC. Only prospective randomized trials were included in the quantitative analysis. Overall and progression-free survival, disease control rate, and transplantation rate were the variables under analysis.Results: Overall survival at 1 year was similar between the two treatment groups (OR =1.31, 95% CI: 0.56&ndash;3.04, P=0.53). Progression-free survival at 1 year was also not statistically different between the two treatments (OR =0.23, 95% CI: 0.02&ndash;2.45, P=0.22). Although a higher proportion of patients underwent transplantation in the TARE group (30% vs 20.8%), this difference was not statistically significant (OR =0.68, 95% CI: 0.23&ndash;2.01; P=0.49).Conclusion: TARE and TACE provide similar outcomes in unresectable HCC. The role of TARE should be explored in selected patient subpopulations in future clinical trials. Keywords: selective internal radiation, SIRT, TARE, TACE, outcome, transplantation rate

Circulating VEGF and eNOS variations as predictors of outcome in metastatic colorectal cancer patients receiving bevacizumab

Novel predictive biomarkers are needed to improve patient selection and optimize the use of bevacizumab (B) in metastatic colorectal cancer. We analyzed the potential of five circulating biomarkers to predict B efficacy and monitor response. Peripheral blood samples collected at baseline, at the first clinical evaluation and at progression were available for 129 patients enrolled in the prospective multicentric ITACa trial and randomized to receive FOLFOX4/FOLFIRI (CT) with (64 patients) or without B (65 patients). VEGF-A, eNOS, EPHB4, COX2 and HIF-1α mRNA levels were measured by qRT-PCR. Baseline marker expression levels and their modulation during therapy were analyzed in relation to objective response, progression-free survival and overall survival (OS). VEGF and eNOS expression was significantly correlated in both groups (Spearman's correlation coefficient = 0.80; P &lt; 0.0001 and 0.75; P &lt; 0.0001, respectively). B-treated patients with &gt;30% reduction in eNOS and VEGF levels from baseline to the first clinical evaluation showed better OS than the others (median OS 31.6 months, 95% CI 21.3-49.5 months and median OS 14.4 months, 95% CI 9.0-22.7 months, respectively, HR 0.38, 95% CI 0.19-0.78, P = 0.008). A reduction in eNOS and VEGF expression from baseline to the first clinical evaluation may indicate a response to B

Venous outflow reconstructions with the piggyback technique in liver transplantation: a single-center experience of 431 cases.

The ideal method of venous outflow reconstruction with the piggyback technique (PB) in orthotopic liver transplantation (OLT) is not well-established. The complications related to PB in 431 primary OLTs were analyzed comparing the orifices used for the anastomosis (cuff of the recipient left and middle hepatic veins [LM], LM with a >1 cm cavoplasty [LM+], or also including the right hepatic vein [LMR]). Treatment strategies and outcome were also evaluated. Twenty patients (4.6%) experienced complications: 13 of 120 (10.8%) with LM, four of 225 (1.8%) with LM+, and three of 86 (3.5%) with LMR (LM versus LM+: P &lt; 0.0001; LM versus LMR: P = NS; LM+ versus LMR = NS). Balloon dilation was successful in 10 of 13 cases in which it was attempted (77%). Eight patients required retransplantation (40%). Three patients (0.7%) died from causes linked to stenosis. Five-year survival of patients with and without complications was 75% and 79%, respectively (P =NS); 5-year graft survival was 50% and 76%, respectively (P = 0.001). The stump formed by the recipient left and middle hepatic veins with a transversal incision >1 cm of the caval wall constantly provides an adequate width for the caval anastomosis with the PB

Expression of connective tissue growth factor is a prognostic marker for patients with intrahepatic cholangiocarcinoma

Background. Connective tissue growth factor is a member of the 'CCN' protein family. Consistent with its profibrotic properties, it is over-expressed in several human epithelial malignancies. Patients and methods. We have retrospectively evaluated by immunohistochemistry the presence of connective tissue growth factor in archival tissues from 55 resected intrahepatic cholangiocarcinomas and compared its expression to the main pathological parameters, disease free and overall survival. Results. Tumours were scored as high and low/absent expressers (≥50%, 0-50% cells, respectively). Thirty-three of 55 cholangiocarcinomas (60%) were high and 22 (40%) low expressers. No significant correlation was found between connective tissue growth factor and tumour grade, tumour location, vascular and perineural invasion. Eighteen of 22 (82%) low/absent expressers and 12/33 (36%) high expressers had recurrence of disease (P = 0.001). Low/absent expressers showed a poor disease free and overall survival compared with the higher expressers (P &lt; 0.001). Vascular invasion was related to tumour recurrence (P = 0.025) and to decreased disease free survival (P &lt; 0.05). During proportional hazard regression analysis, only connective tissue growth factor was found to influence disease free survival (P = 0.01). Conclusions. Expression of connective tissue growth factor is an independent prognostic indicator of both tumour recurrence and overall survival for intrahepatic cholangiocarcinoma patients regardless of tumour location, tumour grade, vascular and perineural invasion. © 2004 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserve

Radiofrequency Ablation of hepatocellular carcinoma: a meta-analysis of overall survival and recurrence-free survival

Andrea Casadei Gardini,1 Giorgia Marisi,2 Matteo Canale,2 Francesco Giuseppe Foschi,3 Gabriele Donati,4 Giorgio Ercolani,5,6 Martina Valgiusti,1 Alessandro Passardi,1 Giovanni Luca Frassineti,1 Emanuela Scarpi7 1Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 2Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; 3Department of Internal Medicine, Degli Infermi Hospital, Faenza, Italy; 4Internal Medicine, Infermi Hospital, AUSL Romagna, Rimini, Italy; 5Department of General Surgery, Morgagni-Pierantoni Hospital, Forl&igrave;, Italy; 6Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; 7Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy Background and aims: So far, no randomized trial or meta-analysis has been conducted on overall survival (OS) and recurrence-free survival (RFS) factors in patients treated with radiofrequency ablation (RFA) alone. The purpose of this meta-analysis was to evaluate prognostic factors of OS and RFS in patients treated with RFA.Methods: A primary analysis was planned to evaluate the clinical prognostic factor of OS. RFS was the secondary aim. Thirty-four studies published from 2003 to 2017 were analyzed. They included 11,216 hepatocellular carcinoma patients.Results: The results showed that Child&ndash;Pugh B vs Child&ndash;Pugh A (HR =2.32; 95% CI: 2.201&ndash;2.69; P&lt;0.0001) and albumin&ndash;bilirubin score 1 vs 0 (HR =2.69; 95% CI: 2.10&ndash;3.44; P&lt;0.0001) were predictive of poor OS. Tumor size as a continuous variable was not predictive of OS, although it was predictive of OS when we considered the size as a cutoff value (&gt;2 cm vs &lt;2 cm: HR =1.41; 95% CI: 1.23&ndash;1.61; P&lt;0.0001; &gt;3 cm vs &lt;3 cm: HR =1.43; 95% CI: 1.17&ndash;1.74; P&lt;0.0001) and in presence of &gt;1 nodule (HR =1.59; 95% CI: 1.46&ndash;1.74; P&lt;0.0001). Alpha-fetoprotein &gt;20 ng/mL (HR =1.46; 95% CI: 1.25&ndash;1.70; P&lt;0.0001) was the only predictive factor of poor prognosis.Conclusion: Our meta-analysis highlighted that the maximum benefit of RFA in terms of OS and RFS is reached in the presence of Child&ndash;Pugh A, albumin&ndash;bilirubin score 1, single-nodule tumor sized &lt;2 cm, and alpha-fetoprotein &lt;20 ng/mL. Keywords: radiofrequency, ALBI score, NLR, outcome, marker , immune-inflammation index, neutrophil-to-lymphocyte ratio, platelet-lymphocyte ratio, chil-pugh, alpha-fetoprotei