Louis Pasteur Hospital

Nice, France

Louis Pasteur Hospital

Nice, France

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Zaanan A.,University Paris - Sud | Costes L.,University Paris - Sud | Gauthier M.,Biostatistics and Epidemiological Unit | Malka D.,University Paris - Sud | And 11 more authors.
Annals of Oncology | Year: 2010

Background: Small-bowel adenocarcinoma (SBA) is a rare tumor of poor prognosis. Data on the efficacy of chemotherapy for advanced SBA are scarce. Patients and methods: All patients with advanced SBA who received frontline chemotherapy from 1996 to 2008 were eligible for this retrospective multicenter study. Results: Ninety-three consecutive patients were included. In the entire population, the median progression-free survival (PFS) and overall survival (OS) times were 6.6 and 15.1 months, respectively. Median PFS times among patients treated with LV5FU2 (n = 10), FOLFOX (n = 48), FOLFIRI (n = 19) and LV5FU2-cisplatin (n = 16) were 7.7, 6.9, 6.0 and 4.8 months, respectively, while median OS times were 13.5, 17.8, 10.6 and 9.3 months, respectively. In multivariate analysis, World Health Organization performance status (PS) (P < 0.0001) and elevated serum levels of carcinoembryonic antigen (CEA) (P = 0.02) and carbohydrate antigen 19-9 (CA 19-9) (P = 0.03) were the only variables significantly associated with poor OS. In the subgroup of patients treated with platinum-based chemotherapy, multivariate analysis showed that LV5FU2-cisplatin was associated with poorer PFS (P < 0.0001) and OS (P = 0.02) compared with FOLFOX. Conclusions: This is the largest study of chemotherapy in advanced SBA. Baseline PS and CEA and CA 19-9 levels were the main prognostic factors. FOLFOX seems to be the most effective platinum-based chemotherapy regimen. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Bastuji-Garin S.,University Paris Est Creteil | Bastuji-Garin S.,Henri Mondor University Hospital | Joly P.,University of Rouen | Lemordant P.,Aix - Marseille University | And 12 more authors.
Journal of Investigative Dermatology | Year: 2011

A rise in the incidence of bullous pemphigoid (BP) was documented recently in Europe, and the main risk factors for BP remain unknown. We conducted a multicenter case-control study to evaluate risk factors for BP. We identified 201 incident BP cases and 345 controls individually matched for age, gender, center, and place of residence (home, nursing home, or extended-care facility). We used univariate and multivariate logistic regression analyses to compare drugs used for over 3 months, comorbidities, and physical and cognitive impairments between cases and controls. Mean age of BP patients was 84.2 (8.7) years. Factors independently associated with BP by multivariate analysis were major cognitive impairment (odds ratio (OR), 2.19; 95% confidence interval (95% CI), 1.24-3.87), bedridden condition (OR, 2.19; 95% CI, 1.23-3.89), Parkinson's disease (OR, 2.16; 95% CI, 1.09-4.27), unipolar or bipolar disorder (OR, 5.25; 95% CI, 1.21-22.86), and chronic use of spironolactone (OR, 2.30; 95% CI, 1.20-4.46) or phenothiazines with aliphatic side chains (OR, 3.70; 95% CI, 1.21-11.34). Chronic analgesic use was associated with a lower risk of BP (OR, 0.49; 95% CI, 0.30-0.81). Thus, risk factors for BP include neurological disorders, particularly dementia and Parkinson's disease, psychiatric disorders (unipolar and bipolar disorders), bedridden condition, and chronic use of several drugs. © 2011 The Society for Investigative Dermatology.


Quoix E.,Hopitaux Universitaires Of Strasbourg | Lena H.,University of Rennes 1 | Losonczy G.,Semmelweis University | Forget F.,Center Hospitalier Of Lardenne | And 19 more authors.
The Lancet Oncology | Year: 2016

Background: MUC1 is a tumour-associated antigen expressed by many solid tumours, including non-small-cell lung cancer. TG4010 is a modified vaccinia Ankara expressing MUC1 and interleukin 2. In a previous study, TG4010 combined with chemotherapy showed activity in non-small-cell lung cancer and the baseline value of CD16, CD56, CD69 triple-positive activated lymphocytes (TrPAL) was shown to be potentially predictive of TG4010 efficacy. In this phase 2b part of the phase 2b/3 TIME trial, we further assess TG4010 in combination with first-line chemotherapy and use of the TrPAL biomarker in this setting. Methods: In this phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial, we recruited previously untreated patients aged 18 years or older with stage IV non-small-cell lung cancer without a known activating EGFR mutation and with MUC1 expression in at least 50% of tumoural cells. Patients were randomly allocated (1:1) by an external service provider to subcutaneous injections of 108 plaque-forming units of TG4010 or placebo from the beginning of chemotherapy every week for 6 weeks and then every 3 weeks up to progression, discontinuation for any reason, or toxic effects, stratified according to baseline value of TrPAL (≤ or > the upper limit of normal [ULN]) and, in addition, a dynamic minimisation procedure was used, taking into account chemotherapy regimen, histology, addition or not of bevacizumab, performance status, and centre. Patients, site staff, monitors, the study funder, data managers, and the statistician were masked to treatment identity. The primary endpoint was progression-free survival, assessed every 6 weeks, to validate the predictive value of the TrPAL biomarker. If patients with TrPAL values of less than or equal to the ULN had a Bayesian probability of more than 95% that the true hazard ratio (HR) for progression-free survival was less than 1, and if those with TrPAL values of greater than the ULN had a probability of more than 80% that the true HR for progression-free survival was more than 1, the TrPAL biomarker would be validated. We did primary analyses in the intention-to-treat population and safety analyses in those who had received at least one dose of study drug and had at least one valid post-baseline safety assessment. Monitors, site staff, and patients are still masked to treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT01383148. Findings: Between April 10, 2012, and Sept 12, 2014, we randomly allocated 222 patients (TG4010 and chemotherapy 111 [50%]; placebo and chemotherapy 111 [50%]). In the whole population, median progression-free survival was 5·9 months (95% CI 5·4-6·7) in the TG4010 group and 5·1 months (4·2-5·9) in the placebo group (HR 0·74 [95% CI 0·55-0·98]; one-sided p=0·019). In patients with TrPAL values of less than or equal to the ULN, the HR for progression-free survival was 0·75 (0·54-1·03); the posterior probability of the HR being less than 1 was 98·4%, and thus the primary endpoint was met. In patients with TrPAL values of greater than the ULN, the HR for progression-free survival was 0·77 (0·42-1·40); the posterior probability of the HR being greater than 1 was 31·3%, and the primary endpoint was not met. We noted grade 1-2 injection-site reactions in 36 (33%) of 110 patients in the TG4010 group versus four (4%) of 107 patients in the placebo group. We noted no grade 3 or 4 nor serious adverse events deemed to be related to TG4010 only. Four (4%) patients presented grade 3 or 4 adverse events related to TG4010 and other study treatments (chemotherapy or bevacizumab) versus 11 (10%) in the placebo group. No serious adverse event was related to the combination of TG4010 with other study treatments. The most frequent severe adverse events were neutropenia (grade 3 29 [26%], grade 4 13 [12%] in the TG4010 group vs grade 3 22 [21%], grade 4 11 [10%] in the placebo group), anaemia (grade 3 12 [11%] vs grade 3 16 [15%]), and fatigue (grade 3 12 [11%], grade 5 one [1%] vs grade 3 13 [12%]; no grade 4 events). Interpretation: TG4010 plus chemotherapy seems to improve progression-free survival relative to placebo plus chemotherapy. These data support the clinical value of the TrPAL biomarker in this clinical setting; because the primary endpoint was met, the trial is to continue into the phase 3 part. Funding: Transgene, Avancées Diagnostiques pour de Nouvelles Approches Thérapeutiques (ADNA), and OSEO. © 2016 Elsevier Ltd.


PubMed | Louis Pasteur Hospital, Departement Hospitalo University, Groupe Hospitalier Of Lest Parisien, Groupe Hospitalier Pitie Salpetriere Charles Foix and University Pierre and Marie Curie
Type: Journal Article | Journal: Journal of the American Geriatrics Society | Year: 2015

To examine the frequency and determinants of underperception of naps in older adults referred for a sleep assessment.Prospective study.Outpatient geriatric sleep clinic.Individuals aged 60 and older referred for insomnia complaints or suspected sleep apnea (N = 135).Tests included clinical interview, sleepiness scale, anxiety and depression scale, Insomnia Severity Index (ISI), Mini-Mental State Examination (MMSE), and overnight polysomnography, followed by multiple sleep latency tests. At the end of each of four nap opportunities, participants answered whether they had slept during the test. Nap underperception was defined as two or more unperceived naps.Of the 105 participants who napped at least twice, 42 (40%) did not perceive at least two naps. These participants had lower MMSE scores (P = .01) and were more likely to be taking benzodiazepines (P = .008) than the 63 participants who did not underperceive their naps but had similar demographic characteristics, sleep diagnoses, depression and anxiety scores, and polysomnography measures. Both groups had similarly short mean daytime sleep latencies (9.7 4.5 minutes and 9.8 3.7 minutes), but participants who underperceived their naps scored lower on the Epworth Sleepiness Scale (5.6 4.0, vs 9.6 4.8, P < .001). An ISI of 11 or greater, a MMSE score of 26 or less, and a sleepiness score of 8 or less were each independently associated with underperception of naps. The combination of these three factors yielded a positive predictive value of 93% and a negative predictive value of 71% for nap underperception.Older adults referred for sleep consultation with cognitive impairment and greater insomnia symptoms frequently underperceive naps, leading them to underestimate their level of sleepiness. In such cases, objective measures of daytime sleepiness would be better than the Epworth Sleepiness Scale.


Sathekge M.,University of Pretoria | Maes A.,AZ Groeninge | Maes A.,University Hospital Leuven | Kgomo M.,Louis Pasteur Hospital | Wiele C.V.D.,Ghent University
Nuclear Medicine Communications | Year: 2010

Objective: To assess prospectively the relationship between fluorodeoxyglucose uptake by lymph nodes, the number of sites of lymph node involvement and cluster of differentiation 4 (CD4) cell count. An inverse relationship, if existing, between these variables would provide indirect support for the concept of homing induced apoptosis. Methods: We evaluated the intensity and extent of fluorodeoxyglucose uptake in lymph nodes of HIV patients under antiviral treatment by means of PET imaging. Quantitative results obtained were related to CD4 cell count and viral loads. Correlation analysis was performed using a nonparametric test and correction for multiple comparisons. Results: Predominant sites of lymph node involvement were the cervical and axillary regions, followed by the inguinal region. CD4 cell count was inversely correlated to the average of the averaged standardized uptake values (SUV) of involved lymph nodes and to the number of sites of lymph node involvement. Viral load was positively correlated to the average of the averaged SUV-mean values of involved lymph nodes and also to the number of sites of lymph nodes involved. An inverse correlation between CD4 cell count and viral load was identified. Conclusion: The inverse relationship between CD4 cell count and the average of the averaged SUV-mean values of involved lymph nodes and between CD4 cell count and the number of sites of lymph node involvement observed, indirectly supports the theory of CD4 cell depletion through forced lymph node homing. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Sathekge M.,University of Pretoria | Maes A.,AZ Groeninge | Maes A.,University Hospital Leuven | Kgomo M.,Louis Pasteur Hospital | And 3 more authors.
Nuclear Medicine Communications | Year: 2010

Objective: To evaluate differences in glucose uptake by skeletal muscle tissue and subcutaneous fat in HIV patients on highly active antiretroviral therapy (HAART) presenting with and without lipodystrophy as well as in drug-naive HIV patients using 18F-fluorodeoxyglucose (FDG) positron emission tomography. Patients and methods: Thirty-nine consecutive patients suffering from HIV: seven drug-naive patients, 21 nonlipodystrophic patients on HAART and 11 patients on HAART, respectively, suffering from lipodystrophy were prospectively included. All patients underwent a whole-body FDG positron emission tomography examination. Standardized uptake values (SUV values) of muscle and subcutaneous fat were compared and related to demographic and biochemical variables. Results: SUV mean values of subcutaneous fat were significantly higher in patients under HAART presenting with lipodystrophy when compared with untreated and treated, nonlipodystrophic patients (P=0.000). SUV mean values of subcutaneous fat significantly correlated with treatment duration (r =0.56, P=0.000) and CD4 count (r=0.51, P= 0.001) and inversely correlated with viral load (r = -0.61, P=0.000). Finally, SUV mean values of thigh muscles were not significantly different between the three different patient groups under study. Conclusion: Quantitative FDG uptake by subcutaneous fat proved significantly higher in HIV patients under HAART presenting with lipodystrophy. HAART did not influence FDG uptake by human skeletal muscle tissue under basal conditions. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Parienti J.-J.,Caen University Hospital Center | Parienti J.-J.,University Pierre and Marie Curie | Du Cheyron D.,Caen University Hospital Center | Timsit J.-F.,French Institute of Health and Medical Research | And 5 more authors.
Critical Care Medicine | Year: 2012

Objective: Catheter-associated infections are common, costly, and potentially lethal. The impact of catheter insertion site on infection risk remains controversial. We aimed to establish whether nontunneled central venous catheters inserted in the subclavian vein are associated with lower risk of catheter-associated infection compared to femoral or internal jugular vein insertion. Data Sources:: We searched MEDLINE (2000-2011), EMBASE (2000-2011), and Cochrane Library plus meta-analyses, gray literature, reference lists, and articles recommended by experts. Study Selection and Extraction: We selected peer-reviewed, randomized, or prospective cohort studies with systematic catheter culture using semiquantitative or quantitative catheter culture techniques and data available for catheter-associated infection by insertion site. Two reviewers independently performed study selection, assessed study quality, and extraction. Discrepancies were resolved by discussion and consensus. Outcomes were mean catheter duration and catheter-associated infection expressed as incidence density per 1000 catheter days. DATA SYNTHESIS:: Ten studies (3250 subclavian, 3053 internal jugular, and 1554 femoral vein) met the inclusion criteria, one of which was randomized (136 subclavian vein and 134 femoral vein). Subclavian vein catheters were left in place significantly longer than alternative catheters (mean difference: 2 days, 95% confidence interval [0.9-3.1], I 2 = 92%, p < .001). The subclavian vein site was associated with fewer catheter-associated infections (1.3 compared to 2.7 per 1000 catheter days for alternative sites, incidence density ratio 0.50; 95% confidence interval [0.33-0.74], I = 0%, p < .001). The same was true when comparisons were stratified by alternative sites (subclavian vein vs. internal jugular vein, incidence density ratio 0.46; 95% confidence interval [0.30-0.70], I 2 = 0%; subclavian vein vs. femoral vein, incidence density ratio 0.27; 95% confidence interval [0.15-0.48], I 2 = 31%). Conclusion: Shortcomings in study design, including channeling, confounding bias, and study heterogeneity, may limit the interpretation of our preliminary study results. Our analysis suggests that the subclavian site may be associated with a lower risk of catheter-associated infection. However, a large, randomized, controlled trial comparing each catheter site complication is warranted before the subclavian site can be unequivocally recommended as a first choice for central venous catheter insertion. © 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.


Doyen J.,Antoine Lacassagne Cancer Center | Doyen J.,University of Nice Sophia Antipolis | Doyen J.,French National Center for Scientific Research | Alix-Panabieres C.,Montpellier University Hospital Center | And 13 more authors.
Critical Reviews in Oncology/Hematology | Year: 2012

Prostate-specific antigen (PSA) levels in blood are widely used in prostate cancer (PCa) for the management of this disease at every stage of progression. Currently, PSA levels combined with clinical stage and Gleason score provide the best predictor of survival and the main element to monitor treatment efficiency. However, these areas could be improved by utilizing emerging biomarkers. Recently, circulating tumor cells (CTCs) and disseminating tumor cells (DTCs) have been detected in PCa and may be a new surrogate candidate. Here we provide a systematic review of the literature in order to describe the current evidence of CTC/DTC surrogacy regarding outcome of prostate cancer patients. We also discuss several markers that could be used to increase the sensitivity and specificity of CTC/DTC detection. CTC/DTC detection is performed using a wide variety of techniques. Initially, reverse transcriptase polymerase chain reaction (RT-PCR) based methods were utilized with weak correlation between their positive detection and patients' outcome. More recent immunological techniques have indicated a reproducible correlation with outcome. Such surrogate markers may enable clinicians to provide early detection for inefficient treatments and patients with poor prognosis that are candidates for treatment intensification. Dissecting the micrometastasis phenomenon in CTCs/DTCs is a key point to increase surrogacy of this biomarker. © 2011 Elsevier Ireland Ltd.


Allaoui M.,Francois Baclesse Cancer Center | Hubert E.,Louis Pasteur Hospital | Michels J.-J.,Francois Baclesse Cancer Center
Turk Patoloji Dergisi/Turkish Journal of Pathology | Year: 2014

Malignant pilomatricoma or pilomatrical carcinoma is a rare malignant hair follicle neoplasm. This tumor is locally aggressive with increased tendency to recur, but a low metastatic potential. Its histopathological diagnosis is difficult and based on a detailed evaluation of the infiltrative nature, the importance of the mummified and necrotic cell component, atypical mitoses, and perineural or vascular invasion. Surgical wide resection is the recommended treatment. It reduces the risk of focal recurrence by 50%. Here we report two new cases including one that occurred on a lesion initially diagnosed as benign pilomatricoma.

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