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Legras A.,Paris Center University Hospitals | Bobbio A.,Paris Center University Hospitals | Magdeleinat P.,Paris Center University Hospitals | Roche N.,University of Paris Descartes | And 3 more authors.
Chest | Year: 2014

Background: A signifi cant percentage of pneumothorax in women is due to thoracic endometriosis. Pathophysiologic mechanisms continue to be debated, and pathologic aspects are poorly known. Methods: Clinical and pathologic records of all consecutive women of reproductive age operated on for pneumothorax between 2000 and 2011 were retrospectively reviewed. Results: Two hundred twenty-nine women (mean age, 33 years) underwent surgery. One hundred forty-four cases (63%) were right-sided, and pneumothoraces were catamenial for 80 women (35%). Diagnosed pelvic endometriosis was associated in 29 cases. At pathology, thoracic endometriosis was diagnosed in 54 cases (24%). Endometrial glands were observed in 33 of 54 cases and were often cystic (16 of 33). Stroma was observed in 51 of 54 cases and endometrial stroma without glands in 21 cases. Hemosiderin-laden macrophages were observed in 27 of 54 cases. All cases of thoracic endometriosis were positive for progesterone and/or estrogen receptors (intense and nuclear). Catamenial pneumothoraces (n 5 80, 34.9%) were endometriosis related in 50% of cases (n 5 40, 17% of the whole population). Pneumothoraces were noncatamenial but endometriosis related in 6% of cases (n 5 14) and merely idiopathic in 60% of patients (n 5 135). Multivariate analysis showed that right side, presence of diaphragmatic abnormalities, relapse after unilateral surgery, and presence of hemosiderin-laden macrophages were independent variables associated with thoracic endometriosis (all, P , .02). Apical emphysema-like changes were found in 184 of the 213 patients (86%) with apical resection and were signifi cantly associated with the absence of thoracic endometriosis ( P , .001). Conclusions: In women with surgically treated pneumothorax, prevalence of catamenial/ endometriosis-related pneumothorax is high. Clinicians and pathologists must be aware to recognize such a diffi cult diagnosis. © 2014 American College of Chest Physicians.


PubMed | Paris Center University Hospitals, University of Paris Descartes and Nice University Hospital Center
Type: Journal Article | Journal: The Annals of thoracic surgery | Year: 2016

Hypothesizing that morphometric measurements are reliable markers of fitness in patients with lung cancer requiring aggressive surgical intervention, the purpose of this study was to assess their impact on postoperative outcome and long-term survival in patients with non-small cell lung cancer (NSCLC) requiring pneumonectomy.Height, weight, and body mass index (BMI), as well as usual clinical, laboratory (including C-reactive protein [CRP] concentrations), and pathologic data were retrospectively retrieved from files of 161 consecutive patients treated by pneumonectomy for NSCLC, whose preoperative computed tomographic (CT) scans were available in the Picture Archive and Communication System (PACS) of the hospital. Cross-sectional areas of right and left psoas areas (measured by CT scan at the L3 level), perirenal fat thickness, and anterior subcutaneous tissue thickness at the left renal vein level were also assessed.BMI and total psoas area were strongly and directly correlated (p= 0.0000001), whereas BMI was inversely related to CRP levels. Sarcopenia (total psoas area 33rd percentile) was associated with high CRP levels (>20 mg/L) (p= 0.010). Factors associated with 90-day mortality included older age (p= 0.000045), lower body weight (p= 0.032), and BMI less than or equal to 25 kg/mBMI less than or equal to 25 kg/m


Benjamin L.,University of Paris Descartes | Benjamin L.,EHESP School of Public Health | Benjamin L.,Glaxosmithkline | Buthion V.,University of Lyon | And 4 more authors.
BMC Health Services Research | Year: 2014

Background: Oral anticancer drugs (OADs) allow treating a growing range of cancers. Despite their convenience, their acceptance by healthcare professionals and patients may be affected by medical, economical and organizational factors. The way the healthcare payment system (HPS) reimburses OADs or finances hospital activities may impact patients' access to such drugs. We discuss how the HPS in France and USA may generate disincentives to the use of OADs in certain circumstances. Discussion. French public and private hospitals are financed by National Health Insurance (NHI) according to the nature and volume of medical services provided annually. Patients receiving intravenous anticancer drugs (IADs) in a hospital setting generate services, while those receiving OADs shift a part of service provision from the hospital to the community. In 2013, two million outpatient IADs sessions were performed, representing a cost of 815 million to the NHI, but positive contribution margin of 86 million to hospitals. Substitution of IADs by OADs mechanically induces a shortfall in hospital income related to hospitalizations. Such economic constraints may partially contribute to making physicians reluctant to prescribe OADs. In the US healthcare system, coverage for OADs is less favorable than coverage for injectable anticancer drugs. In 2006, a Cancer Drug Coverage Parity Act was adopted by several states in order to provide patients with better coverage for OADs. Nonetheless, the complexity of reimbursement systems and multiple reimbursement channels from private insurance represent real economic barriers which may prevent patients with low income being treated with OADs. From an organizational perspective, in both countries the use of OADs generates additional activities related to physician consultations, therapeutic education and healthcare coordination between hospitals and community settings, which are not considered in the funding of hospitals activities so far. Summary. Funding of healthcare services is a critical factor influencing in part the choice of cancer treatments and this is expected to become increasingly important as economic constraints grow. Drug reimbursement systems and hospital financing changes, coupled with other accompanying measures, should contribute to improve equal and safe patient access to appropriate anticancer drugs and improve the management and care pathway of cancer patients. © 2014 Benjamin et al.; licensee BioMed Central Ltd.


Bujan L.,EA 3694 Human Fertility Research Group | Bujan L.,Toulouse 1 University Capitole | Walschaerts M.,Toulouse 1 University Capitole | Moinard N.,Toulouse 1 University Capitole | And 15 more authors.
Fertility and Sterility | Year: 2013

Objective: To determine the consequences of adjuvant testicular germ cell tumor treatment (TGCT) on sperm characteristics and sperm DNA, and to evaluate the predictors of sperm recovery. Design: Multicenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months. Setting: University hospitals. Patient(s): One hundred twenty-nine volunteer TGCT patients and a control group of 257 fertile men. Intervention(s): Routine semen analyses, sperm DNA, and chromatin assessments. Main Outcome Measure(s): Comparisons of mean sperm characteristics before and after treatment, with sperm recovery analyzed by the Kaplan-Meier method. Result(s): The quantitative and qualitative sperm characteristics decreased after treatment, with lowest values at 3 and 6 months and with variations according to treatment type. The mean total sperm count recovered to pretreatment values at 12 months after treatment after two or fewer bleomycin, etoposide, and cisplatin (BEP) cycles, but not after radiotherapy or more than two BEP cycles. Only the treatment modalities and pretreatment sperm production were related to recovery of the World Health Organization reference sperm values. An increased proportion of patients had elevated high sperm DNA stainability at 6 months after radiotherapy. Conclusion(s): Adjuvant treatments for testicular germ cell tumor have drastic effects on spermatogenesis and sperm chromatin quality. These new data on both the recovery period according to treatment modalities and the post-treatment chromatin status of sperm are useful tools for counseling patients wishing to conceive. © 2013 by American Society for Reproductive Medicine.


Bujan L.,University Paul Sabatier | Walschaerts M.,University Paul Sabatier | Brugnon F.,Federation Francaise des CECOS | Brugnon F.,Universitary Hospital Estaing | And 13 more authors.
Fertility and Sterility | Year: 2014

Objective To determine consequences of lymphoma treatments on sperm characteristics and sperm DNA, and to evaluate predictors of sperm recovery. Design Multicenter prospective longitudinal study of patients analyzed before treatment and after 3, 6, 12, and 24 months. Setting University hospitals. Patient(s) Seventy-five Hodgkin lymphoma and non-Hodgkin lymphoma patients and a control group of 257 fertile men. Intervention(s) Semen analyses, and sperm DNA and chromatin assessments. Main Outcome Measure(s) Comparisons of sperm characteristics before and after treatment. Result(s) Patients already had altered sperm characteristics before lymphoma treatment, with no identified risk factor. Sperm count, total sperm count, motility, and vitality decreased after treatment, with lowest values at 3 and 6 months. Twelve months after treatment, mean sperm count recovered to pretreatment values after doxorubicin, bleomycin, vinblastine, darcarbacine (ABVD) or ABVD + radiotherapy, but not after doxorubicin, cyclophosphamide, vincristine, prednisone (CHOP) or mechlorethamine, oncovin, procarbazine, prednisone (MOPP) chemotherapies. It was noteworthy that 7% of patients remained azoospermic at 24 months. After 24 months, Kaplan-Meier estimates showed that more than 90% of patients will recover normal sperm count after ABVD or ABVD + radiotherapy vs. 61% for CHOP chemotherapies. In multivariate analyses including diagnosis and treatment protocol, only pretreatment total sperm count was related to recovery. Compared with a control group, lymphoma patients had higher sperm chromatin alterations and DNA fragmentation before any treatment. After treatment, DNA fragmentation assessed by TUNEL assay and sperm chromatin structure assay decreased from 3 and 6 months, respectively, while remaining higher than in the control group during follow-up. Conclusion(s) Lymphoma patients had altered sperm DNA and chromatin before treatment. Lymphoma treatment had damaging effects on spermatogenesis. These data on both the recovery period according to treatment modalities and the pre- and post-treatment chromatin status of sperm are useful tools for counseling patients wishing to conceive. © 2014 by the American Congress of Rehabilitation Medicine.


Sellmann C.,Friedrich - Schiller University of Jena | Jin C.J.,Friedrich - Schiller University of Jena | Degen C.,Friedrich - Schiller University of Jena | De Bandt J.,University of Paris Descartes | And 2 more authors.
Journal of Nutrition | Year: 2015

Background: Genetic factors, a diet rich in fat and sugar, and an impaired intestinal barrier function are critical in the development of nonalcoholic steatohepatitis (NASH). The nonessential amino acid glutamine (Gln) has been suggested to have protective effects on intestinal barrier function but also against the development of liver diseases of various etiologies. Objective: The effect of oral Gln supplementation on the development of Western-style diet (WSD)-induced NASH in mice was assessed. Methods: Female 6- to 8-wk-old C57BL/6J mice were pair-fed a control (C) diet or a WSD alone or supplemented with 2.1 g L-Gln/kg body weight for 6 wk (C+Gln or WSD+Gln). Indexes of liver damage, lipid peroxidation, and glucose metabolism and endotoxin concentrations were measured. Results: Although Gln supplementation had no effect on the loss of the tight junction protein occludin, the increased portal endotoxin and fasting glucose concentrations found inWSD-fed mice,markers of liver damage (e.g., nonalcoholic fatty liver disease activity score and number of neutrophils in the liver) were significantly lower in the WSD+Gln group than in the WSD group (~47% and ~60% less, respectively; P < 0.05). Concentrations of inducible nitric oxide synthase (iNOS) protein and 3-nitrotyrosin protein adducts were significantly higher in livers of WSD-fed mice than in all other groups (~8.6- and ~1.9-fold higher, respectively, compared with the C group; P < 0.05) but did not differ between WSD+Gln-, C-, and C+Gln-fed mice. Hepatic tumor necrosis factor a and plasminogen activator inhibitor 1 concentrations were significantly higher in WSD-fed mice (~1.6- and ~1.8-fold higher, respectively; P < 0.05) but not in WSD +Gln-fed mice compared with C mice. Conclusion: Our data suggest that the protective effects of oralGln supplementation on the development ofWSD-inducedNASH in mice are associated with protection against the induction of iNOS and lipid peroxidation in the liver. © 2015 American Society for Nutrition.


PubMed | Paris Center University Hospitals, University of Paris Descartes and Friedrich - Schiller University of Jena
Type: Comparative Study | Journal: The Journal of nutrition | Year: 2015

Fructose induces nonalcoholic fatty liver disease (NAFLD). Citrulline (Cit) may exert a beneficial effect on steatosis.We compared the effects of Cit and an isonitrogenous mixture of nonessential amino acids (NEAAs) on fructose-induced NAFLD.Twenty-two male Sprague Dawley rats were randomly assigned into 4 groups (n = 4-6) to receive for 8 wk a 60% fructose diet, either alone or supplemented with Cit (1 g kg(-1) d(-1)), or an isonitrogenous amount of NEAAs, or the same NEAA-supplemented diet with starch and maltodextrin instead of fructose (controls). Nutritional and metabolic status, liver function, and expression of genes of hepatic lipid metabolism were determined.Compared with controls, fructose led to NAFLD with significantly higher visceral fat mass (128%), lower lean body mass (-7%), insulin resistance (135%), increased plasma triglycerides (TGs; 67%), and altered plasma amino acid concentrations with decreased Arg bioavailability (-27%). This was corrected by both NEAA and Cit supplementation. Fructose caused a 2-fold increase in the gene expression of fatty acid synthase (Fas) and 70% and 90% decreases in that of carnitine palmitoyl-transferase 1a and microsomal TG transfer protein via a nearly 10-fold higher gene expression of sterol regulatory element-binding protein-1c (Srebp1c) and carbohydrate-responsive element-binding protein (Chrebp), and a 90% lower gene expression of peroxisome proliferator-activated receptor (Ppara). NEAA or Cit supplementation led to a Ppara gene expression similar to controls and decreased those of Srebp1c and Chrebp in the liver by 50-60%. Only Cit led to Fas gene expression and Arg bioavailability similar to controls.In our rat model, Cit and NEAAs effectively prevented fructose-induced NAFLD. On the basis of literature data and our findings, we propose that NEAAs may exert their effects specifically on the liver, whereas Cit presumably acts at both the hepatic and whole-body level, in part via improved peripheral Arg metabolism.


Schull A.,Paris Center University Hospitals | Monzani Q.,Paris Center University Hospitals | Bour L.,Paris Center University Hospitals | Barry-Delongchamps N.,Paris Center University Hospitals | And 3 more authors.
Diagnostic and Interventional Imaging | Year: 2012

In epididymo-orchitis, a sonogram shows a non-homogenous and hypertrophied epididymis and testis, with increased vascularisation seen on a Doppler sonogram. Abscesses must be investigated using sonography so that a necrotic tumour is not misdiagnosed. In prostatitis, sonography is indicated to investigate urine retention and where treatment has failed (to look for a blockage, an abscess, or pyelonephritis). Endorectal sonography is the best imaging modality for analysing the parenchyma, but otherwise has limited value. Chronic prostatitis is the main differential diagnosis from prostate cancer; the two may be distinguished using diffusion MRI. In cases of cystitis, imaging is indicated when a patient has recurrent cystitis (to investigate what the causative factors might be), or an infection with a less common bacterium (to look for calcifications, emphysema, any involvement of the upper urinary tract), and in cases of cystitis with pseudotumour. © 2012 Published by Elsevier Masson SAS on behalf of the Éditions françaises de radiologie.


Bobbio A.,Paris Center University Hospitals | Alifano M.,Paris Center University Hospitals | Alifano M.,University of Paris Descartes
Pharmacological Research | Year: 2015

Surgery is still the best treatment option of lung cancer but only one third of patients are operable and prognosis remains mediocre in operated patients, with the exception of initial stages. Medical treatment is fast moving toward new frontiers. New insights in the biology of cancer development led to discovery of new drugs, which are more effective as compared to conventional platinum based chemotherapy. A new approach to immunotherapy based on immune-check point represents a remarkable innovation in lung cancer treatment. Initial trials with anti PD-1 antibodies in metastatic patients provided results never observed with previously known drug categories. Several key question need to be answered to identify patients most likely to respond to anti PD-1/anti PD-L1 treatments, to assess the role of combined treatment modalities including immune check point receptor block (associations with surgery, chemotherapy, ITKs), and to boost host immune response, possibly by lowering his systemic inflammation and improving nutritional status. © 2015 Elsevier Ltd. All rights reserved.


PubMed | Paris Center University Hospitals, Unit of thoracic Surgery, University of Paris Descartes and University Pierre and Marie Curie
Type: Journal Article | Journal: PloS one | Year: 2014

Hypothesizing that nutritional status, systemic inflammation and tumoral immune microenvironment play a role as determinants of lung cancer evolution, the purpose of this study was to assess their respective impact on long-term survival in resected non-small cell lung cancers (NSCLC).Clinical, pathological and laboratory data of 303 patients surgically treated for NSCLC were retrospectively analyzed. C-reactive protein (CRP) and prealbumin levels were recorded, and tumoral infiltration by CD8+ lymphocytes and mature dendritic cells was assessed. We observed that factors related to nutritional status, systemic inflammation and tumoral immune microenvironment were correlated; significant correlations were also found between these factors and other relevant clinical-pathological parameters. With respect to outcome, at univariate analysis we found statistically significant associations between survival and the following variables: Karnofsky index, American Society of Anesthesiologists (ASA) class, CRP levels, prealbumin concentrations, extent of resection, pathologic stage, pT and pN parameters, presence of vascular emboli, and tumoral infiltration by either CD8+ lymphocytes or mature dendritic cells and, among adenocarcinoma type, tumor grade (all p<0.05). In multivariate analysis, prealbumin levels (Relative Risk (RR): 0.34 [0.16-0.73], p=0.0056), CD8+ cell count in tumor tissue (RR=0.37 [0.16-0.83], p=0.0162), and disease stage (RR 1.73 [1.03-2.89]; 2.99[1.07-8.37], p=0.0374- stage I vs II vs III-IV) were independent prognostic markers. When taken together, parameters related to systemic inflammation, nutrition and tumoral immune microenvironment allowed robust prognostic discrimination; indeed patients with undetectable CRP, high (>285 mg/L) prealbumin levels and high (>96/mm2) CD8+ cell count had a 5-year survival rate of 80% [60.9-91.1] as compared to 18% [7.9-35.6] in patients with an opposite pattern of values. When stages I-II were considered alone, the prognostic significance of these factors was even more pronounced.Our data show that nutrition, systemic inflammation and tumoral immune contexture are prognostic determinants that, taken together, may predict outcome.

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