Natural Course of Nonmalignant Partial Portal Vein Thrombosis in Cirrhotic Patients

Background/Aim:

Portal vein thrombosis (PVT) has a high incidence in patients with liver cirrhosis and determines a poor prognosis of hepatic disease. The aim of our study was to define the natural course of partial PVT in cirrhotic patients, including survival and decompensation rates.

Patients and Methods:

We performed a prospective, cohort study, in a tertiary referral center. There were 22 cirrhotic patients with partial nonmalignant PVT, without anticoagulant treatment, who were followed-up between January 2011 and October 2013. All patients were evaluated by Doppler abdominal ultrasound and computed tomography. Kaplan–Meier method was used to determine the difference in clinical events between the study subgroups.

Results:

After a mean follow-up period of 20.22 months, partial PVT improved in 5 (22.73%), was stable in 11 (50%), and worsened in 6 (27.27%) patients. Hepatic decompensation rate at 6 and 18 months was higher in patients with worsened PVT than in those with stable/improved PVT (50% vs. 25%, P < 0.0001 and 100% vs. 56.25%, P < 0.0001, respectively). The survival rate at 6 months was 66.66% in worsened PVT group vs. 81.25% (P = 0.005) in stable/improved group, and 16.66% vs. 81.25% (P < 0.0001) at 18 months, respectively. Multivariate analysis showed that Model of End-Life Disease was the independent predictor of hepatic decompensation [hazard ratio (HR) 1.42; 95% confidence interval (CI): 1.08−1.87, P = 0.012] and survival (HR 1.76; 95% CI: 1.06−2.92, P = 0.028).

Conclusions:

Nonmalignant partial PVT remained stable/improved in over half of cirrhotic patients and aggravated in more than one fourth in whom it negatively influenced the survival and decompensation rates.     

Salecan-Clay Based Polymer Nanocomposites for Chemotherapeutic Drug Delivery Systems; Characterization and In Vitro Biocompatibility Studies

Salecan is a microbial polysaccharide suitable to obtain hydrogel for biomedical applications due to the excellent hydrophilicity and biocompatibility properties. In this work, Salecan of different concentrations was introduced into polymethacrylic acid (PMAA) in the presence of clay to form novel semi synthetic hydrogel nanocomposites systems and loaded afterwards with doxorubicin (DOX). The physical–chemical characteristics of the nanocomposites systems and their effect on the viability, and morphology of MDBK (Madin–Darby bovine kidney), HT-29 human colorectal adenocarcinoma and Colo 205 human colon adenocarcinoma cell lines were investigated. DOX release from the nanocomposite systems, cell up-take and subsequent effect on cell proliferation was also analyzed. It was found that Salecan concentration determined the swelling behavior, structural parameters and morphological features of the nanocomposite systems. The hydrogen bonds strongly influenced the formation of PMAA–Salecan–clay systems, each component bringing its own contribution, thus demonstrating the achievement of an advanced crosslinked network and a more compacted hydrogel nanocomposite morphology. All the synthesized nanocomposites had negligible toxicity to normal MDBK cells and chemoresistent HT-29 cell line, whereas in the case of Colo 205 cells a decrease by 40% of the cell viability was obtained for the sample containing the highest amount of Salecan. This effect was correlated with the lowest pore size distribution leading to highest available specific surface area and entrapped amount of DOX which was further released from the nanocomposite sample. Corroborating all the data it can be suggested that the synthesized nanocomposites with Salecan and clay could be good candidates as vehicles for chemotherapeutic agents.     

Combined modality therapy versus chemotherapy alone as an induction regimen for primary central nervous system lymphoma: a decision analysis

In immunocompetent patients with primary central nervous system (CNS) lymphoma, combined modality therapy (CMT) using high‐dose methotrexate and whole brain radiotherapy has improved response rates compared to chemotherapy alone. The trade‐off is delayed and potentially devastating treatment‐related neurotoxicity. A Markov decision‐analytic model compared CMT to chemotherapy alone in patients with primary CNS lymphoma. Baseline probabilities were derived from a systematic literature review. Outcomes were life expectancy and quality‐adjusted life expectancy. Sensitivity analyses were performed. The life expectancy was 2·69 years for CMT and 2·77 years for chemotherapy alone. The quality‐adjusted life expectancies for the two strategies were 1·70 and 1·67 quality‐adjusted life years (QALYs) respectively. In younger patients <60 years of age, CMT yielded a quality‐adjusted life expectancy of 2·71 QALYs, compared to 2·09 QALYs for chemotherapy alone, yielding an expected benefit with CMT of 0·62 QALYs or 7·4 quality‐adjusted months. There was no difference between the strategies in the older group. The model was robust to key variables for the younger group. The preferred induction strategy for younger patients appears to be CMT, maximizing life expectancy, and QALYs. This analysis confirms that the preferred strategy for older patients is chemotherapy alone.     

Prognostic value of pulsed tissue Doppler imaging for the assessment of left ventricular systolic function in patients with nonischemic dilated cardiomyopathy

There is still some debate regarding the prognostic significance of left ventricular longitudinal systolic dysfunction as assessed by tissue Doppler (TD) imaging in patients with chronic heart failure (HF), since previous studies have included patients with postischemic wall motion abnormalities. Thus, this study was designed to ascertain whether TD-derived longitudinal systolic dysfunction may influence the outcome of patients with nonischemic chronic HF. In 200 consecutive patients with chronic HF secondary to dilated cardiomyopathy and no history of ischemic heart disease, peak systolic mitral annular velocity (S(m) ) was measured by pulsed TD at the septal and lateral annular sites. The end points were cardiac death or hospitalization for worsening HF. Mean follow-up duration was 30 months. In a time independent analysis, averaged S(m) calculated as the average of septal and lateral S(m) , resulted to be a significant predictor of outcome in the study population (area under receiver-operator characteristic curve: cardiovascular death, 0.69, P < 0.0001; cardiovascular events, 0.64, P = 0.0005). In a time-dependent analysis, average S(m) was associated with both cardiovascular death (hazard ratio 0.832, P = 0.0019) and cardiovascular events (hazard ratio 0.904, P = 0.039), independently of other clinical risk factors and echocardiographic parameters of systolic function. Septal S(m) but not lateral S(m) was independently associated with the outcome measures. In conclusion, the assessment of systolic mitral annular velocity by pulsed TD is a useful indicator for prognostic stratification of patients with nonischemic dilated cardiomyopathy and chronic HF.     

Androgen receptor aberrations in the era of abiraterone and enzalutamide

Prostate cancer is the most prevalent non-skin cancer and the second leading cause of cancer death in men of the western world. As growth and differentiation of prostate cancer largely depend on androgens, inhibition of the androgen/androgen receptor signaling axis is the main treatment for locally advanced and/or metastatic tumors. Although first-line androgen deprivation therapies like chemical/surgical castration and/or administration of anti-androgens are able to control the disease for several years, prostate cancer almost invariably recurs as castration-resistant prostate cancer. This stage of the disease is characterized by a sustained AR-signaling despite castrate levels of circulating androgens. Various molecular mechanisms were shown to induce castration resistance. This review will discuss the most recent and relevant experimental findings on AR-signaling in castration-resistant prostate cancer in order to provide a comprehensive interpretation of the clinical behavior of this tumor entity following treatments with abiraterone, enzalutamide, ARN-509 or taxanes.