How to diagnose and manage hepatic encephalopathy: a consensus statement on roles and responsibilities beyond the liver specialist.

Introduction: Hepatic encephalopathy is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting. Symptoms include nonspecific cognitive impairment, personality changes and changes in consciousness. Overt (symptomatic) hepatic encephalopathy is a common complication of cirrhosis that is associated with a poor prognosis.

Quantification of CT-assessed radiation-induced lung damage in lung cancer patients treated with or without chemotherapy and cetuximab.

Background And Purpose: Prediction models for radiation-induced lung damage (RILD) are still unsatisfactory, with clinical toxicity endpoints that are difficult to quantify objectively. We therefore evaluated RILD more objectively, quantitatively and on a continuous scale measuring the lung tissue density changes per voxel.

Material And Methods: Patients treated with radiotherapy (RT) alone, sequential and concurrent chemo-RT with and without the addition of cetuximab were studied.

DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer.

Background: Prostate cancer (PCa) is a very heterogeneous disease with respect to clinical outcome. This study explored differential DNA methylation in a priori selected genes to diagnose PCa and predict clinical failure (CF) in high-risk patients.

Methods: A quantitative multiplex, methylation-specific PCR assay was developed to assess promoter methylation of the APC, CCND2, GSTP1, PTGS2 and RARB genes in formalin-fixed, paraffin-embedded tissue samples from 42 patients with benign prostatic hyperplasia and radical prostatectomy specimens of patients with high-risk PCa, encompassing training and validation cohorts of 147 and 71 patients, respectively.

Drug disposition and modelling before and after gastric bypass: immediate and controlled-release metoprolol formulations.

Aims: The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled-release formulation before and after Roux-en-Y gastric bypass (RYGB) surgery in the same individuals and to validate a physiologically based pharmacokinetic (PBPK) model for predicting oral bioavailability following RYGB.

Methods: A single-dose pharmacokinetic study of metoprolol tartrate 200 mg immediate release and controlled release was performed in 14 volunteers before and 6-8 months after RYGB. The observed data were compared with predicted results from the PBPK modelling and simulation of metoprolol tartrate immediate and controlled-release formulation before and after RYGB.

Focus on treatment complications and optimal management: radiation oncology.

Background: Esophagitis and pneumonitis are the most important treatment complications and dose-limiting toxicities in non-small cell lung cancer (NSCLC) patients treated with radiotherapy (RT) alone or combined modality therapy.

Methods: A literature research was performed to identify published articles relating clinical and dosimetric parameters associated with significant radiation pneumonitis (RP) and esophagitis in NSCLC patients treated with three-dimensional conformal RT.

Results: Possible clinical parameters associated with acute and or late esophagitis are concurrent chemoradiation, hyperfractionated and accelerated radiation regimens, dysphagia and neutropenia during treatment.

Individualized positron emission tomography-based isotoxic accelerated radiation therapy is cost-effective compared with conventional radiation therapy: a model-based evaluation.

Purpose: To evaluate long-term health effects, costs, and cost-effectiveness of positron emission tomography (PET)-based isotoxic accelerated radiation therapy treatment (PET-ART) compared with conventional fixed-dose CT-based radiation therapy treatment (CRT) in non-small cell lung cancer (NSCLC).

Methods And Materials: Our analysis uses a validated decision model, based on data of 200 NSCLC patients with inoperable stage I-IIIB. Clinical outcomes, resource use, costs, and utilities were obtained from the Maastro Clinic and the literature.

Multistate Statistical Modeling: A Tool to Build a Lung Cancer Microsimulation Model That Includes Parameter Uncertainty and Patient Heterogeneity.

With the shift toward individualized treatment, cost-effectiveness models need to incorporate patient and tumor characteristics that may be relevant to treatment planning. In this study, we used multistate statistical modeling to inform a microsimulation model for cost-effectiveness analysis of individualized radiotherapy in lung cancer. The model tracks clinical events over time and takes patient and tumor features into account.

NHS-IL2 combined with radiotherapy: preclinical rationale and phase Ib trial results in metastatic non-small cell lung cancer following first-line chemotherapy.

Background: NHS-IL2 (selectikine, EMD 521873, MSB0010445) consists of human NHS76 (antibody specific for necrotic DNA) fused to genetically modified human interleukin 2 (IL-2) and selectively activates the high-affinity IL-2 receptor. Based on an evolving investigational concept to prime the tumor microenvironment with ionizing radiation prior to initiating immunotherapy, 2 related studies were conducted and are reported here. The first, a preclinical study, tests the systemic effect of the immunocytokine NHS-IL2 and radiotherapy in a lung carcinoma animal model; the second, a phase Ib trial in patients with metastatic non-small cell lung carcinoma (NSCLC), was designed to determine the safety and tolerability of NHS-IL2 in combination with radiotherapy directly following first-line palliative chemotherapy.

Fatal bilateral pneumonitis after locoregional thoracic chemoradiation in a transplanted patient under immunosuppressive therapy.

Background: After thoracic radiotherapy a pneumonitis may occur, mostly confined to the irradiated volume of the lung. In general, it resolves spontaneously without long-term effects.

Case Report: A 68-year-old man was diagnosed with a stage IIIA adenocarcinoma of the lung and was treated with sequential chemoradiation.

Vessel based delineation guidelines for the elective lymph node regions in breast cancer radiation therapy - PROCAB guidelines.

Objective: A national project to improve the quality of breast radiation therapy was started, named PROCAB (PROject on CAncer of the Breast). One of the objectives was to reach a national consensus guideline for the delineation of the regional lymph node areas in breast radiation therapy.

Methods: The realization of the new guidelines was a step by step process that started with multiple expert meetings where the existing guidelines were analyzed and the delineations of the lymph node regions were performed together with a surgeon, specialized in the anatomy of the drainage of the breast.

High-dose re-irradiation following radical radiotherapy for non-small-cell lung cancer.

As the prognosis of lung cancer patients improves, more patients are at risk of developing local recurrence or a new primary tumour in previously irradiated areas. Technological advances in radiotherapy and imaging have made treatment of patients with high-dose re-irradiation possible, with the aim of long-term disease-free survival and even cure. However, high-dose re-irradiation with overlapping volumes of previously irradiated tissues is not without risks.

Everolimus in acute kidney injury in a patient with breast cancer: a case report.

Introduction: Everolimus, a mammalian target of Rapamycin inhibitor, has recently been approved for the treatment of metastatic estrogen receptor-positive breast cancer, in combination with exemestane at a daily dose of 10mg. In the literature, few cases of acute kidney injury have been reported related to everolimus use, but none of them in a patient with breast cancer as we report here. Our case report of acute kidney injury demonstrates the potential nephrotoxic effects of everolimus therapy, necessitating close monitoring of renal function prior to, during and after discontinuation of the drug.

In vivo quantification of hypoxic and metabolic status of NSCLC tumors using [18F]HX4 and [18F]FDG-PET/CT imaging.

Purpose: Increased tumor metabolism and hypoxia are related to poor prognosis in solid tumors, including non-small cell lung cancer (NSCLC). PET imaging is a noninvasive technique that is frequently used to visualize and quantify tumor metabolism and hypoxia. The aim of this study was to perform an extensive comparison of tumor metabolism using 2[(18)F]fluoro-2-deoxy-d-glucose (FDG)-PET and hypoxia using HX4-PET imaging.

A longitudinal evaluation of partial lung irradiation in mice by using a dedicated image-guided small animal irradiator.

Purpose: In lung cancer radiation therapy, the dose constraints are determined mostly by healthy lung toxicity. Preclinical microirradiators are a new tool to evaluate treatment strategies closer to clinical irradiation devices. In this study, we quantified local changes in lung density symptomatic of radiation-induced lung fibrosis (RILF) after partial lung irradiation in mice by using a precision image-guided small animal irradiator integrated with micro-computed tomography (CT) imaging.

Impact of hypoalbuminemia on voriconazole pharmacokinetics in critically ill adult patients.

Setting the adequate dose for voriconazole is challenging due to its variable pharmacokinetics. We investigated the impact of hypoalbuminemia (<35 g/liter) on voriconazole pharmacokinetics in adult intensive care unit (ICU) patients treated with voriconazole (20 samples in 13 patients) as well as in plasma samples from ICU patients that had been spiked with voriconazole at concentrations of 1.5 mg/liter, 2.

Surgical and nonsurgical approaches to small-size nonsmall cell lung cancer.

Lobectomy and systematic nodal dissection are still the standard for small-size (<3 cm) nonsmall cell lung cancer. There is growing interest in more parenchyma-sparing surgery, so-called sublobar resections (wedge resection or segmentectomy). Indeed, nonrandomised trials suggest that a segmentectomy may result in local control rates that are similar to lobectomy.

A phase I study of concurrent individualized, isotoxic accelerated radiotherapy and cisplatin-vinorelbine-cetuximab in patients with stage III non-small-cell lung cancer.

Background: In this open-label phase I study, the maximum-tolerated dose of cetuximab with concurrent chemoradiotherapy (C-CRT) in stage III non-small-cell lung cancer together with individualized, isotoxic accelerated radiotherapy (RT) was investigated.

Methods: Patients with stage III non-small-cell lung cancer, World Health Organization performance status 0-1, forced expiratory volume in 1 second more than 50%, carbon monoxide diffusing capacity more than 50%, weight loss less than 10%, and no severe comorbidity were enrolled. Patients without progression after one to two cycles of gemcitabine-carboplatin were included and treated with cetuximab 400 mg/kg d7 and 250 mg/kg weekly together with RT and cisplatin (50 mg/m d1, 8; 40 mg/m d22)-vinorelbine for 5 weeks.

Imaging techniques for tumour delineation and heterogeneity quantification of lung cancer: overview of current possibilities.

Imaging techniques for the characterization and delineation of primary lung tumours and lymph nodes are a prerequisite for adequate radiotherapy. Numerous imaging modalities have been proposed for this purpose, but only computed tomography (CT) and FDG-PET have been implemented in clinical routine. Hypoxia PET, dynamic contrast-enhanced CT (DCE-CT), dual energy CT (DECT) and (functional) magnetic resonance imaging (MRI) hold promise for the future.

Volumetric CT-based segmentation of NSCLC using 3D-Slicer.

Accurate volumetric assessment in non-small cell lung cancer (NSCLC) is critical for adequately informing treatments. In this study we assessed the clinical relevance of a semiautomatic computed tomography (CT)-based segmentation method using the competitive region-growing based algorithm, implemented in the free and public available 3D-Slicer software platform. We compared the 3D-Slicer segmented volumes by three independent observers, who segmented the primary tumour of 20 NSCLC patients twice, to manual slice-by-slice delineations of five physicians.