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Hôpital-Camfrout, France

Elkrief L.,University Paris Diderot | Chouinard P.,University Paris Diderot | Bendersky N.,HOpital Beaujon | Hajage D.,AP HP | And 10 more authors.
Hepatology | Year: 2014

In patients with chronic hepatitis C (CHC), cirrhosis is associated with age, gender, diabetes, alcohol abuse, and coinfection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV). The effect of these factors on the outcome of cirrhosis is unknown. This study in CHC patients with cirrhosis aimed to assess the influence of these factors on decompensation, liver transplantation, and death. Consecutive patients with CHC and cirrhosis hospitalized between January 1, 2006 and December 31, 2008 were followed up until death, transplantation, or study closure in March 2013. Gender, age, Model for End-Stage Liver Disease (MELD) score, diabetes, alcohol abuse, HIV, or HBV coinfection were collected at inclusion. The complications of cirrhosis, death, and liver transplantation were recorded at inclusion and during follow-up. The association between baseline factors and liver-related outcomes at inclusion and during follow-up were tested using logistic regression and Cox's model, respectively. A total of 348 patients with CHC and cirrhosis (68% men; median age: 59 years; median MELD: 10) were included. At baseline, 40% of the patients had diabetes, 29% alcohol abuse, and 6% HIV or HBV coinfection. Baseline MELD ≥10 (P<0.001), diabetes (P=0.027), and HBV coinfection (P=0.001) were independently associated with transplantation-free survival. Baseline diabetes was independently associated with ascites (P=0.05), bacterial infections (P=0.001), and encephalopathy (P<0.001) at inclusion. Baseline diabetes was independently associated with development of ascites (P=0.057), renal dysfunction (P=0.004), bacterial infections (P=0.007), and hepatocellular carcinoma (P=0.016) during the follow-up. Conclusion: In patients with CHC and cirrhosis, diabetes is an independent prognostic factor. Improving diabetes control may improve the outcome of cirrhosis. © 2014 by the American Association for the Study of Liver Diseases. Source

Vacher C.,University Paris Diderot | Lkah C.,HOpital Beaujon
Journal of Plastic, Reconstructive and Aesthetic Surgery | Year: 2010

Free tissue transfer has become the dominant reconstructive tool for segmental defects of the mandible, except in case of severe peripheral vascular disease. In these cases, we propose to use the osteomuscular dorsal scapular (OMDS) flap as an alternative technique. This flap is pedicled on the dorsal scapular vessels with the harvesting of the medial border of the scapula and the lateral part of the rhomboid muscles. Methods: Thirteen cadaveric dissections have been performed after arterial injection of coloured latex in order to describe the surgical landmarks of the dorsal scapular pedicle. Six patients have been operated after lateral resection of the mandible. Results: The mean length of the pedicle was 66 mm (±2.61). The pedicle was located 41.2 mm (±5.51) lateral to the superior angle and 24.6 mm (±7.50) lateral to the medial angle. The size of the medial border that could be used for mandibular reconstruction was 116.46 mm (±7.48). The width of the medial border was 2.62 mm (±0.77) on the upper part and 3.35 mm (±0.90) on the inferior part. The clinical results were satisfying; good symmetry of the mandible was restored with normal opening of the mouth. Normal elevation of the shoulder was retained without recourse to physiotherapy. Discussion: The advantages of this method over other pedicled flaps include the length of the bone that can be harvested (>12 cm) allowing reconstruction of defects from the condylar process to the canine region and the preservation of scapular elevation. The superior part of the trapezius was not harvested, in order to allow passage of the flap in the tunnel under the upper trapezius to preserve the scapular elevation. The main disadvantages of the OMDS flap are the impossibility of placing implants in the bone that have been harvested because of its thickness and the lateral position that has to be changed to supine to allow access for resection of the tumour. © 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Source

Ozenne V.,HOpital Beaujon
European journal of gastroenterology & hepatology | Year: 2010

BACKGROUND: Sorafenib is the standard treatment for patients with an advanced stage of hepatocellular carcinoma (HCC). The aims of this study were (i) to evaluate the tolerance and survival of sorafenib-treated patients, in a nonselected population, especially in Child-Pugh B patients; and (ii) to identify potential prognostic factors of survival. PATIENTS AND METHODS: From April 2007 to December 2008, 50 patients received sorafenib for advanced HCC. Seventeen (34%) were Child-Pugh B patients. We recorded adverse events and the duration of treatment and survival. For 34 patients with histopathologically proven HCC, immunophenotypical analysis was carried out using antibodies against cluster differentiation 34, vascular endothelial growth factor, phosphorylated ERK, cytokeratin 19, and phosphorylated stat3. RESULTS: Patients with Child-Pugh B cirrhosis had a more advanced stage of the disease compared with Child-Pugh A patients. The occurrence of adverse events was similar in Child-Pugh A and Child-Pugh B patients. Duration of treatment until discontinuation for bad tolerance was lower in Child-Pugh B patients (1.8 vs. 5 months, P=0.02). Survival of Child-Pugh A patients was higher compared with Child-Pugh B patients (8.9 vs. 2 months, P=0.004). Barcelona Clinic Liver Cancer stage, Eastern Cooperative Oncology Group Performance Status, portal vein impairment, extra-hepatic spread, and alpha-foetoprotein were also prognostic factors. In multivariate analysis, the sole factor associated with survival was the Barcelona Clinic Liver Cancer stage. None of the immunohistological markers used was associated with tolerance and survival. CONCLUSION: Occurrence of adverse events is similar in Child-Pugh A and Child-Pugh B patients. Nevertheless, the survival of Child-Pugh B patients is very low. Whether liver function or tumor spread is responsible for mortality is unclear. Opportunity of treatment for Child-Pugh B patients is questionable. The immunophenotype of tumoral tissue was not predictive of survival. Source

Asselah T.,HOpital Beaujon | Asselah T.,French Institute of Health and Medical Research
Journal of Hepatology | Year: 2011

Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Gao M, Nettles RE, Belema M, Snyder LB, Nguyen VN, Fridell RA, Serrano-Wu MH, Langley DR, Sun JH, O'Boyle DR 2nd, Lemm JA, Wang C, Knipe JO, Chien C, Colonno RJ, Grasela DM, Meanwell NA, Hamann LG. Nature. 2010;465(7294):96-100. Copyright (2010). Abstract reprinted with permission from Macmillan Publishers Ltd. http://www.ncbi.nlm.nih.gov/pubmed/20410884 Abstract: The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people. Current therapy relies upon a combination of pegylated interferon-alpha and ribavirin, a poorly tolerated regimen typically associated with less than 50% sustained virological response rate in those infected with genotype 1 virus. The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B. Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations (EC(50)) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture. In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log(10) reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus. Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system. These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Source

Frilling A.,Imperial College London | Modlin I.M.,Yale University | Kidd M.,Yale University | Russell C.,University College London | And 11 more authors.
The Lancet Oncology | Year: 2014

Many management strategies exist for neuroendocrine liver metastases. These strategies range from surgery to ablation with various interventional radiology procedures, and include both regional and systemic therapy with diverse biological, cytotoxic, or targeted agents. A paucity of biological, molecular, and genomic information and an absence of data from rigorous trials limit the validity of many publications detailing management. This Review represents the views from an international conference, for which 15 expert working groups prepared evidence-based assessments addressing specific questions, and from which an independent jury derived final recommendations. The aim of the conference was to review the existing approaches to neuroendocrine liver metastases, assess the evidence on which management decisions were based, develop internationally acceptable recommendations for clinical practice (when evidence was available), and make recommendations for clinical and research endeavours. This report represents the final clinical statements and proposals for future research. © 2014 Elsevier Ltd. Source

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