Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial.

BACKGROUND: Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC) in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. METHODS: The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky >or=60%/Child-Pugh <or= 12) were randomised to receive thymostimulin 75 mg s.c. 5x/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS), time to progression (TTP), tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC) formed part of the protocol. RESULTS: Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6]) or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]). Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. CONCLUSIONS: In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN64487365

Documentary evidence of past floods in Europe and their utility in flood frequency estimation

International audienceThis review outlines the use of documentary evidence of historical flood events in contemporary flood frequency estimation in European countries. The study shows that despite widespread consensus in the scientific literature on the utility of documentary evidence, the actual migration from academic to practical application has been limited. A detailed review of flood frequency estimation guidelines from different countries showed that the value of historical data is generally recognised, but practical methods for systematic and routine inclusion of this type of data into risk analysis are in most cases not available. Studies of historical events were identified in most countries, and good examples of national databases attempting to collate the available information were identified. The conclusion is that there is considerable potential for improving the reliability of the current flood risk assessments by harvesting the valuable information on past extreme events contained in the historical data sets.Cet article présente une revue de l'utilisation de l'information documentaire sur les crues historiques par les pays européens pour l'analyse fréquentielle des crues. L'étude montre que, malgré l'existence d'un consensus scientifique sur l'intérêt de ce type d'information, son utilisation reste encore limitée d'un point de vue opérationnel. Si les guides pratiques sur l'estimation des crues mentionnent en général bien l'intérêt de l'information historique, il existe encore peu de logiciel disponible utilisant cette information. Des travaux sont en cours dans plusieurs pays pour constituer des bases de données nationales sur les crues historiques. La conclusion est qu'il y aurait un fort bénéfice à exploiter ces informations pour l'estimation du risque de crue

Augmented virtuality based on stereoscopic reconstruction in multimodal image-guided neurosurgery: methods and performance evaluation.: Augmented Virtuality Based on Stereoscopic Reconstruction in Multimodal Image-Guided Neurosurgery: Methods and Performance Evaluation

Displaying anatomical and physiological information derived from preoperative medical images in the operating room is critical in image-guided neurosurgery. This paper presents a new approach referred to as augmented virtuality (AV) for displaying intraoperative views of the operative field over three-dimensional (3-D) multimodal preoperative images onto an external screen during surgery. A calibrated stereovision system was set up between the surgical microscope and the binocular tubes. Three-dimensional surface meshes of the operative field were then generated using stereopsis. These reconstructed 3-D surface meshes were directly displayed without any additional geometrical transform over preoperative images of the patient in the physical space. Performance evaluation was achieved using a physical skull phantom. Accuracy of the reconstruction method itself was shown to be within 1 mm (median: 0.76 mm +/- 0.27), whereas accuracy of the overall approach was shown to be within 3 mm (median: 2.29 mm +/- 0.59), including the image-to-physical space registration error. We report the results of six surgical cases where AV was used in conjunction with augmented reality. AV not only enabled vision beyond the cortical surface but also gave an overview of the surgical area. This approach facilitated understanding of the spatial relationship between the operative field and the preoperative multimodal 3-D images of the patient

Virtualité augmentée en neurochirurgie guidée par l'image

National audienceLes développements considérables de la neuro-imagerie moderne permettent une meilleure préparation des procédures de neurochirurgie guidée par l'image en zones éloquentes [9]. Ces informations, de nature multimodale, anatomiques et fonctionnelles, sont également accessibles durant la procédure chirurgicale grâce à l'utilisation de systèmes de neuronavigation permettant la mise en correspondance géométrique entre les images pré opératoires et le patient. La visualisation des images pré opératoires durant la procédure chirurgicale est un point crucial en neurochirurgie moderne. La plupart des systèmes de neuronavigation permettent d'afficher, dans les oculaires du microscope, les images pré opératoires du patient en superposition avec la vue du champ opératoire, définissant ainsi le concept de réalité augmentée [3]. Les images superposées sont les intersections des volumes d'intérêt et du plan focal du microscope. En outre, elles sont le plus souvent bidimensionnelles et monochromes alors que ces informations sont tridimensionnelles et multimodales [6]. Cette situation limite considérablement la reconnaissance et l'interprétation des images superposées. Dans ce papier, nous décrivons une méthode originale dite de virtualité augmentée. Le principe est de reconstruire la surface tridimensionnelle du champ opératoire à partir des vues stéréoscopiques obtenues par l'intermédiaire du microscope opératoire et de superposer cette surface à la scène virtuelle pré opératoire pendant l'intervention

Performance Evaluation of a Stereoscopic Based 3D Surface Localiser for Image-Guided Neurosurgery

International audienc