Lyon University Hospital Center
Lyon University Hospital Center
Coy S.,Lyon University Hospital Center
American Journal of Surgical Pathology | Year: 2017
Papillary tumor of the pineal region (PTPR) is a neuroepithelial neoplasm first described in 2003. Despite the anatomic association of PTPR with the pineal gland, the features of these tumors resemble those of the ependymal circumventricular subcommissural organ (SCO) of the posterior third ventricle. Given the presumed distinct derivation of PTPR and pineal parenchymal tumors, we hypothesized that expression of lineage-specific transcription factors could distinguish these tumors and provide additional insight into the differentiation of PTPR. A broad series of pineal region samples was reviewed, including 7 benign pineal glands, 4 pineal cysts, 13 pineocytomas, 28 pineal parenchymal tumors of intermediate differentiation, 11 pineoblastomas, and 18 PTPR. All samples were evaluated by immunohistochemistry for expression of CRX, a master transcriptional regulator of photoreceptor differentiation expressed in pineal gland and retina and/or FOXJ1, a master transcriptional regulator of ciliogenesis expressed in normal ependymal cells and ependymal neoplasms. Diffuse nuclear CRX expression is present in 100% of pineal samples. FOXJ1 is negative in all pineal samples. CRX staining is present in 53% of PTPR, though expression is nearly always limited to rare cells. Diffuse nuclear FOXJ1 expression is present in 100% of PTPR. Fetal human SCO diffusely expressed FOXJ1 but was negative for CRX. Immunohistochemistry for FOXJ1 and CRX differentiates non–germ cell pineal region tumors with high sensitivity and specificity, including pineal parenchymal tumors and PTPR. Our findings support the hypothesis that PTPR have ependymal differentiation and are phenotypically more similar to SCO than pineal gland. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Roselyne B.,Lyon University Hospital Center
Therapeutic Drug Monitoring | Year: 2017
BACKGROUND:: The implication of inosine triphosphate pyrophosphatase (ITPA) on thiopurine drug response variability has been investigated but little data is available on its role on thiopurine metabolites. ITPA’ ability to modify the thiopurine metabolite levels currently used to optimize azathioprine (AZA) therapy in relation to TPMT activity, the aim of this study is to investigate ITPA phenotype in a large population and to evaluate the relation between ITPA and TPMT activities and thiopurine metabolites. METHODS:: ITPA activity was determined in 183 adults and 138 children with or without azathioprine therapy. 6-thioguanine nucleotides (6-TGN), 6-methylmercaptopurine nucleotides (6-MeMPN) levels and ITPA as well as TPMT activities were measured in red blood cells. Using the Gaussian mixture model, distribution of ITPA activity was evaluated. Intraindividual variability and influence of age, sex, AZA treatment and associated co-medications on ITPA activity were also assessed. RESULTS:: This retrospective study shows a quadrimodal distribution in ITPA activity. No influence of age, sex, AZA therapy and co-medications was found. In adults, ITPA activity was not significantly associated with 6-TGN or 6-MeMPN concentrations while a weak negative correlation was observed with 6-MeMPN levels in pediatric populations (rs=-0.261; p=0.024). A weak positive correlation was observed between ITPA and TPMT activities in children (rs=0.289; p=0.001). CONCLUSIONS:: ITPA activity was poorly influenced by non-genetic parameters and has no influence on 6-TGN and 6-MeMPN concentrations in adults and only a weak correlation with 6-MeMPN and TPMT activity in children. These results demonstrate that ITPA is not a rate-limiting enzyme in the formation of 6-TGN but suggest that a decrease in ITPA activity in children may be a risk factor for accumulation of 6-MeMPN in cells. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Abdel M.P.,Mayo Medical School |
Oussedik S.,University College London |
Parratte S.,Aix - Marseille University |
Lustig S.,Lyon University Hospital Center |
Haddad F.S.,22 Buckingham Street
Bone and Joint Journal | Year: 2014
Substantial healthcare resources have been devoted to computer navigation and patientspecific instrumentation systems that improve the reproducibility with which neutral mechanical alignment can be achieved following total knee replacement (TKR). This choice of alignment is based on the long-held tenet that the alignment of the limb post-operatively should be within 3° of a neutral mechanical axis. Several recent studies have demonstrated no significant difference in survivorship when comparing well aligned versus malaligned TKRs. Our aim was to review the anatomical alignment of the knee, the historical and contemporary data on a neutral mechanical axis in TKR, and the feasibility of kinematicallyaligned TKRs. Review of the literature suggests that a neutral mechanical axis remains the optimal guide to alignment. © 2014 The British Editorial Society of Bone & Joint Surgery.
Cordier J.-F.,Lyon University Hospital Center |
Cottin V.,Lyon University Hospital Center
Seminars in Respiratory and Critical Care Medicine | Year: 2011
Diffuse alveolar hemorrhage (DAH) in primary and secondary vasculitis occurs when capillaritis is present. The diagnosis of DAH is considered in patients who develop progressive dyspnea with alveolar opacities on chest imaging (with density ranging from ground glass to consolidation) that cannot be explained otherwise. Hemoptysis, a valuable sign, is often absent. A decline of blood hemoglobin level over a few days without hemolysis or any hemorrhage elsewhere should be an alert for DAH. Bronchoalveolar lavage, retrieving bright red fluid, is the best diagnostic clue. Lung biopsy is not recommended. A search for anti-neutrophil cytoplasmic autoantibodies (ANCAs) is mandatory. Once DAH is diagnosed and hemodynamic as well as infectious causes have been excluded, ANCA-associated vasculitis is taken into account (mainly microscopic polyangiitis or Wegener granulomatosis, and, exceptionally, Churg-Strauss syndrome). Drug-induced DAH, especially antithyroid drugs such as propylthiouracil may be coupled with ANCA. Isolated DAH with capillaritis with or without ANCA is rare. DAH in systemic lupus erythematosus is either associated or not with capillaritis. Treatment of DAH should target the underlying disorder. In the primary vasculitides, corticosteroids and immunosuppressants, especially cyclophosphamide, are the mainstay of therapy, but plasma exchange, particularly in severe DAH, is the rule, although evidence of its effectiveness is awaited. © 2011 by Thieme Medical Publishers, Inc.
Michallet M.,Lyon University Hospital Center
Journal of medical economics | Year: 2011
Acute myeloblastic leukaemia (AML) patients are at high risk of suffering from invasive fungal infections (IFI). Posaconazole demonstrated higher efficacy than standard azole agents (SAA) in the prophylaxis of IFI in this population. The authors estimated the cost effectiveness of posaconazole versus SAA in France. A decision-tree model was developed to compare posaconazole with SAA with the results of a published clinical trial. Clinical events were modelled with chance nodes reflecting probabilities of IFI, IFI-related death, and death from other causes. Medical resource consumption and costs were obtained from results of the clinical trial and from a dedicated survey on the costs of treating IFI using a retrospective chart review design. IFI treatment costs were estimated using medical files from 50 AML patients from six French centres, with a proven and probable IFI, who had been followed-up for 298 days on average. Direct costs directly related to IFI were estimated at €51,033, including extra costs of index hospitalisation, costs of antifungal therapy and additional hospitalisations related to IFI treatment. The model indicated that the healthcare costs for the posaconazole strategy were €5,223 (€2,697 for prophylaxis and €2,526 for IFI management), which was €859 less than the €6,083 in costs with SAA (€469 for prophylaxis and €5614 for IFI management). A sensitivity analysis indicated that there was an 80% probability that prophylaxis using the posaconazole strategy would be superior. The findings from this analysis suggest that posaconazole use is a clinically and economically dominant strategy in the prophylaxis of IFI in AML patients, given the usual limits of economic models and the uncertainty of costs estimates.
Revol O.,Lyon University Hospital Center |
Milliez N.,Lyon University Hospital Center |
Gerard D.,Lyon University Hospital Center
British Journal of Dermatology | Year: 2015
Summary The psychological consequences of acne have been the subject of many studies. As a particularly visible skin disorder, acne complicates the daily lives of adolescents who are undergoing multiple transformations: physical, intellectual and emotional. While it is well established that acne can be responsible for depression and low self-esteem, it is likely that this impact is aggravated by the sociological evolution of adolescents in the 21st century. Understanding the codes of adolescents today (who can be characterized as being more concerned by their appearance than previous generations at the same age) allows us to optimize our medical approach to acne and facilitates treatment compliance and adherence. © 2015 British Association of Dermatologists.
Lustig S.,Lyon University Hospital Center
Orthopaedics and Traumatology: Surgery and Research | Year: 2014
Patellofemoral arthroplasty remains controversial, primarily due to the high failure rates reported with early implants. Several case series have been published over the years, which describe the results with various first- and second-generation implants. The purpose of this work was to summarize results published up to now and identify common themes for implants, surgical techniques, and indications. First-generation resurfacing implants had relatively high failure rates in the medium term. Second-generation implants, with femoral cuts based on TKA designs, have yielded more promising medium-term results. The surgical indications are quite specific and must be chosen carefully to minimize poor results. Short-term complications are generally related to patellar maltracking, while long-term complications are generally related to progression of osteoarthritis in the tibiofemoral joint. Implant loosening and polyethylene wear are rare. Overall, recent improvements in implant design and surgical techniques have resulted in better short- and medium-term results. But more work is required to assess the long-term outcomes of modern implant designs. © 2013 Elsevier Masson SAS.
Des Portes V.,Lyon University Hospital Center
Handbook of Clinical Neurology | Year: 2013
Ten percent of cases of intellectual deficiency in boys are caused by genes located on the X chromosome. X-linked mental retardation (XLMR) includes more than 200 syndromes and 80 genes identified to date. The fragile X syndrome is the most frequent syndrome, due to a dynamic mutation with a CGG triplet amplification. Mental retardation is virtually always present. Phonological and syntactic impairments are often combined with pragmatic language impairment and visuospatial reasoning difficulties. A minority fulfill the criteria for autism. In girls, the clinical expression of the complete mutation varies according to the X chromosome inactivation profile. Several XLMR occur as severe early onset encephalopathies: Lowe oculocerebrorenal syndrome, ATR-X syndrome (alpha thalassemia/mental retardation X-linked), Allan-Herdon-Dudley syndrome (MCT8 gene). Two genes, ARX (X-LAG; Partington syndrome) and MECP2 (Rett syndrome in females; mild MR with spastic diplegia/psychotic problems in males) are associated with various phenotypes, according to the mutation involved. Oligophrenine 1 (OPHN-1) gene mutations lead to vermal dysplasia. PQBP1 gene mutations (Renpenning syndrome) are responsible for moderate to severe mental deficiency, microcephaly, and small stature. Although some forms of XLMR are not very specific and the phenotype for each given gene is somewhat heterogeneous, a clinical diagnostic strategy is emerging. © 2013 Elsevier B.V.
Uzzan M.,Lyon University Hospital Center
Annals of Surgery | Year: 2016
OBJECTIVES:: To determine the cumulative incidence and the prognostic factors of ileorectal anastomosis (IRA) failure after colectomy for ulcerative colitis (UC). BACKGROUND:: Although ileal pouch-anal anastomosis is recommended after colectomy for UC, IRA is still performed. METHODS:: This was a multicenter retrospective cohort study, which included patients with IRA for UC performed between 1960 and 2014. IRA failure was defined as secondary proctectomy and/or rectal cancer occurrence. Uni- and multivariate survival analyses were performed using Cox-proportional hazards models. RESULTS:: A total of 343 patients from 13 French centers were included. Median follow up after IRA was 10.6 years. IRA failure rates were estimated at 27.0% (95% confidence interval, CI, 22–32) and 40.0% (95% CI 33–47) at 10 and 20 years, respectively. Median survival time without IRA failure was estimated at 26.8 years. Two thirds of secondary proctectomies were performed for refractory proctitis, and 20% for rectal neoplasia. Univariate analysis identified factors associated with IRA failure: IRA performed after 2005, a longer duration of disease at the time of IRA, indication for colectomy and having received immunomodulative agents before IRA. In multivariate analysis, treatment with both immunosuppressant (IS) and anti-TNF before colectomy was independently associated with IRA failure (HR=2.9, 95% CI 1.2–7.1). Conversely, colectomy for severe acute colitis was associated with decreased risk of IRA failure (HR=0.6, 95% CI 0.4–0.97). DISCUSSION:: Patients with UC have a high risk of IRA failure, particularly when colectomy is performed for refractory disease. However, IRA could be discussed after colectomy for severe acute colitis, or in patients naive to IS and anti-TNF. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Denost Q.,Lyon University Hospital Center
Annals of Surgery | Year: 2016
OBJECTIVE:: To assess the effect of pelvic drainage after rectal surgery for cancer. BACKGROUND:: Pelvic sepsis is one of the major complications after rectal excision for rectal cancer. Although many studies have confirmed infectiveness of drainage after colectomy, there is still a controversy after rectal surgery. METHODS:: This multicenter randomized trial with 2 parallel arms (drain vs no drain) was performed between 2011 and 2014. Primary endpoint was postoperative pelvic sepsis within 30 postoperative days, including anastomotic leakage, pelvic abscess, and peritonitis. Secondary endpoints were overall morbidity and mortality, rate of reoperation, length of hospital stay, and rate of stoma closure at 6 months. RESULTS:: A total of 494 patients were randomized, 25 did not meet the criteria and 469 were analyzed: 236 with drain and 233 without. The anastomotic height was 3.5?±?1.9?cm from the anal verge. The rate of pelvic sepsis was 17.1% (80/469) and was similar between drain and no drain: 16.1% versus 18.0% (P = 0.58). There was no difference of surgical morbidity (18.7% vs 25.3%; P = 0.83), rate of reoperation (16.6% vs 21.0%; P = 0.22), length of hospital stay (12.2 vs 12.2; P = 0.99) and rate of stoma closure (80.1% vs 77.3%; P = 0.53) between groups. Absence of colonic pouch was the only independent factor of pelvic sepsis (odds ratio = 1.757; 95% confidence interval 1.078–2.864; P = 0.024). CONCLUSIONS:: This randomized trial suggests that the use of a pelvic drain after rectal excision for rectal cancer did not confer any benefit to the patient. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.