Frilling A.,Imperial College London |
Modlin I.M.,Yale University |
Kidd M.,Yale University |
Russell C.,University College London |
And 12 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.
Marcellin P.,Hopital Beaujon
Revue du Praticien | Year: 2011
In recent years, marked progress has been made in the treatment of chronic hepatitis B. Several agents have been approved: interferon alpha-(IFN), pegylated interferon alpha2a (PEG-IFN alpha2a), lamivudine, adefovir, entecavir, telbivudine and recently, tenofovir. Each drug has advantages and limitations. IFN and PEG-IFN alpha2a have the advantage of inducing a sustained virologic response after a defined, limited course of treatment. However, these drugs are only effective in a minority of patients and have frequent side effects. Analogues have the advantage of being administered orally, with good safety profiles and a potent antiviral effect. However, these drugs need to be administered indefinitely since withdrawal of therapy is generally associated with reactivation, and a sustained response is uncommon except in HBeAg positive patients who develop HBe seroconversion. In case of HBe seroconversion, therapy should usually be continued for at least another 24 weeks. The efficacy of lamivudine is limited by the emergence of lamivudine-resistant HBV. Adefovir is associated with a moderate incidence of resistance but its antiviral effect is not optimal. Entecavir has shown to be more effective with a favourable safety profile and a low incidence of resistance. Telbivudine is more potent and has a lower rate of resistance than lamivudine but the resistance rate is significantly higher than other approved drugs. Tenofovir has a potent antiviral effect with a good resistance profile.
Mac-Thiong J.-M.,University of Montréal |
Roussouly P.,Center Medico Chirurgical Of Readaptation Des Massues |
Berthonnaud E.,Hopital Villefranche |
Guigui P.,Hopital Beaujon
European Spine Journal | Year: 2011
Introduction: Many studies suggest the importance of the sagittal sacropelvic balance and morphology in spinal and hip disorders. This study describes the normal age- and sex-related changes in sacropelvic morphology and balance in a prospective cohort of asymptomatic adults without spinal disorder. Materials and methods: A prospective cohort of 709 asymptomatic adults without spinal pathology was recruited. There were 354 males and 355 females aged 37.9 ± 14.7 and 35.7 ± 13.9 years, respectively. For each subjects, pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were measured from standing lateral radiographs. Ratios of SS to PI (SS/PI), PT to PI (PT/PI), and PT to SS (PT/SS) were also calculated. Results: There was no significant difference in PI (pelvic incidence), SS (sacral slope), PT (pelvic tilt), PT/PI, SS/PI, or PT/SS between males and females. The mean ± 2 standard deviations (SD) range was 32°-74°, 0°-27°, and 24°-55° for PI, PT and SS, respectively. The mean ± 2 SD range was greater than 0.5 for SS/PI and less than 0.5 for PT/PI. PI was not related to age in either sex group. PT, SS, PT/PI, SS/PI, and PT/SS presented only weak correlation coefficients (r ≤ 0.21) with respect to age. Conclusion: The current study presents the largest cohort of asymptomatic adults in the literature dedicated to the evaluation of sagittal sacropelvic morphology and balance. The range of values corresponding to the mean ± 2 SD can provide invaluable information to clinicians about the normal range of values expected in 95% of the normal population. © 2011 Springer-Verlag.
Charosky S.,Polyclinique du Parc |
Guigui P.,Hopital Beaujon |
Blamoutier A.,CHP St Gregoire |
Roussouly P.,Center des Massues |
Chopin D.,Institute Calot
Spine | Year: 2012
Study Design.: A multicentric retrospective study on primary adult scoliosis patients operated on between 2002 and 2007. A 3-step statistical analysis was performed to describe the incidence of complications, the risk factors, and the reoperation risk with survival curves for the entire cohort. Objective.: To describe complication rate and risk factors as well as survival curves associated with adult primary scoliosis surgery in patients aged 50 years or older. Summary of Background Data.: Adult deformity surgery is classically associated with a high rate of complications. The identification of risk factors for developing such complications is consequently of major interest as well as survival curves that can provide useful information on reoperation risks. Although many reports exist in the literature, the cohorts analyzed are often heterogeneous and the actual prevalence of complications varies widely. This study represents to our knowledge the largest series on adult patients aged 50 years or older operated for the first time for lumbar or thoracolumbar scoliosis and excluding every other possible diagnosis. Methods.: A retrospective review of prospectively collected data from 6 centers in France. A total of 306 primary lumbar adult or degenerative scoliosis patients older than 50 years undergoing surgery between 2002 and 2007 were included. Demographics, comorbidities, x-ray parameters, surgical data, and complications were analyzed. Statistical analysis was performed to obtain correlations and risk factors for developing complications. Reoperation risk was calculated with Kaplan-Meier survival curves. Results.: A total of 306 patients aged 63 years (range, 50-83), with 83% women. Mean follow-up was 54 months. Mean Cumulative Illness Rating Scale score was 5 (range, 0-26). Main curve was 50° (range, 4-96) with apex between T12 and L2. Ten percent of patients had anterior surgery only, 18% had double anteroposterior approach, and 72% had posterior surgery only. Seventy-four percent (226 patients) had long fusions of 3 or more levels and 44% (134 patients) were fused to the sacrum. Forty percent (122 patients) had a decompression performed and 18% had an osteotomy. There were 175 complications for 119 patients (39%). No cases of death or blindness were reported. General complication rate was 13.7%, early infection occurred in 4% (12 patients), and late infection occurred in 1.2%. Neurological complications were present in 7% with 2 cases (0.6%) of late cord-level deficits and 12 reoperations (4%). Prevalence of mechanical complications was 24% (73 patients), with 58 patients (19%) needing a reoperation. Risk factors for mechanical or neurological complications were number of instrumented vertebra (P ≤ 0.01) fusion to the sacrum (P ≤ 0.001), pedicle subtraction osteotomy (PSO) (P=0.01), and a high preoperative pelvic tilt of 26° or more (P ≤ 0.05). Kaplan-Meier survival curves showed reoperation risk of 44% at 70 months. Long fusion risk was 40% at 50 months and fusions to the sacrum reoperation risk was 48% at 49 months. Conclusion.: Overall complication rate was 39%, and 26% of the patients were reoperated for mechanical or neurological complications. Risk factors include number of instrumented vertebra, fusion to the sacrum, PSO, and preoperative pelvic tilt of 26° or more. There is a 44% risk of a new operation in the 6-year-period after the primary procedure. © 2012 Lippincott Williams & Wilkins.
Patel K.,Duke University |
Bedossa P.,Physiology and Imaging |
Castera L.,Hopital Beaujon
Seminars in Liver Disease | Year: 2015
Abstract The diagnostic assessment of liver fibrosis, a major determinant of disease severity, is an important step in the management of patients with chronic liver diseases. Liver biopsy is still considered the gold standard for the assessment of necroinflammation and fibrosis; however, recent technical advances have resulted in the development of numerous serum biomarkers and imaging tools as noninvasive alternatives to biopsy. These tests include biological (serum biomarker algorithms), physical (imaging assessment of tissue stiffness), and physiological (breath test) methods. Accumulating evidence shows that noninvasive tests provide prognostic information of clinical relevance, which has led to their incorporation into clinical guidelines and everyday practice. Here, the authors review and compare invasive and noninvasive tests for the diagnosis of liver fibrosis. They discuss emerging functional genomic, microparticle, protein-profiling, and bioimaging tools, focusing on novel sensitive tools that are able to assess the dynamic nature of fibrogenesis, a key requirement for the assessment of the efficacy of antifibrotic compounds in the future. Copyright © 2015 by Thieme Medical Publishers.
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.
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.
Bedossa P.,Hopital Beaujon |
Patel K.,University of Toronto
Gastroenterology | Year: 2016
Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of histopathologic features, ranging from isolated hepatic steatosis, to steatohepatitis with evidence of hepatocellular injury and fibrosis, to cirrhosis. The diagnosis and determination of NAFLD prognosis requires clinical and histopathologic assessments. Liver biopsy still is regarded as the reference for differentiating steatosis (NAFL) from nonalcoholic steatohepatitis, for staging hepatic fibrosis, and for identifying NAFLD in patients with other chronic liver disease. Standardized grading and staging histologic scoring systems, such as the NAFLD activity score and the steatosis, activity, and fibrosis score, can help guide clinical decisions and assess outcomes of clinical trials. Improved understanding of the pathophysiology of NAFLD and technologic advances have led to algorithms that can be used to assess serum biomarkers and imaging methods that are noninvasive alternatives to biopsy collection and analysis. We review the advantages and limitations of biopsy analysis and noninvasive tests as diagnostic and prognostic tools for patients with NAFLD. We also discuss techniques to improve dynamic histopathology assessment, and emerging blood and imaging biomarkers of fibrogenesis. © 2016 AGA Institute.
Benoist M.,Hopital Beaujon |
Boulu P.,Pain Unit |
Hayem G.,Bichat Teaching Hospital
European Spine Journal | Year: 2012
Introduction Epidural steroid injections (ESIs) have been widely used for over 50 years in the treatment of low-back pain with radiculopathy. Most interventional pain physicians strongly believe in their efficacy and safety. Recent Cochrane systematic reviews have disclosed controversial results and have questioned the effectiveness of ESIs. Moreover, a few neurological adverse events have been reported recently. Methods A literature search of systematic reviews analysing the effectiveness and complications of ESIs was carried out. The scientific quality of the reviews was assessed using the validated index of Oxman and Guyatt.Werelied on data abstraction and quality ratings of the placebo-controlled trials as reported by high-quality systematic reviews. Results Two types of systematic reviews were found. The Cochrane high-quality systematic reviews combining the three approaches and different pathologies were predominantly non-conclusive. The second type of review, emanating from the US Evidence-based Practice Centers, distinguishing between the routes of administration and between the principal pathologies found a moderate shortterm benefit of ESIs versus placebo in patients with disc herniation and radiculitis, in keeping with the clinical experience. ESIs are generally well tolerated and most complications are related to technical problems. Cases of paraplegia, complicating the foraminal route and related to the violation of a radiculomedullary artery, have been recently reported. They are predominantly observed in previously operated patients. Conclusions Epidural steroid injections have a moderate short-term effect in the management of low-back pain with radiculopathy. Severe neurological complications are exceptional, but call for research for alternative approaches to the foramen as well as for means to detect an eventual arterial injury. © 2011 Springer-Verlag.
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.