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Boegemann M.,University of Munster | Stephan C.,Charité - Medical University of Berlin | Stephan C.,Urologic | Cammann H.,Charité - Medical University of Berlin | And 6 more authors.
BJU International | Year: 2016

Objectives To prospectively test the diagnostic accuracy of the percentage of prostate specific antigen (PSA) isoform [-2]proPSA (%p2PSA) and the Prostate Health Index (PHI), and to determine their role for discrimination between significant and insignificant prostate cancer at initial and repeat prostate biopsy in men aged ≤65 years. Patients and Methods The diagnostic performance of %p2PSA and PHI were evaluated in a multicentre study. In all, 769 men aged ≤65 years scheduled for initial or repeat prostate biopsy were recruited in four sites based on a total PSA (t-PSA) level of 1.6-8.0 ng/mL World Health Organization (WHO) calibrated (2-10 ng/mL Hybritech-calibrated). Serum samples were measured for the concentration of t-PSA, free PSA (f-PSA) and p2PSA with Beckman Coulter immunoassays on Access-2 or DxI800 instruments. PHI was calculated as (p2PSA/f-PSA × √t-PSA). Uni- and multivariable logistic regression models and an artificial neural network (ANN) were complemented by decision curve analysis (DCA). Results In univariate analysis %p2PSA and PHI were the best predictors of prostate cancer detection in all patients (area under the curve [AUC] 0.72 and 0.73, respectively), at initial (AUC 0.67 and 0.69) and repeat biopsy (AUC 0.74 and 0.74). t-PSA and %f-PSA performed less accurately for all patients (AUC 0.54 and 0.62). For detection of significant prostate cancer (based on Prostate Cancer Research International Active Surveillance [PRIAS] criteria) the %p2PSA and PHI equally demonstrated best performance (AUC 0.70 and 0.73) compared with t-PSA and %f-PSA (AUC 0.54 and 0.59). In multivariate analysis PHI we added to a base model of age, prostate volume, digital rectal examination, t-PSA and %f-PSA. PHI was strongest in predicting prostate cancer in all patients, at initial and repeat biopsy and for significant prostate cancer (AUC 0.73, 0.68, 0.78 and 0.72, respectively). In DCA for all patients the ANN showed the broadest threshold probability and best net benefit. PHI as single parameter and the base model + PHI were equivalent with threshold probability and net benefit nearing those of the ANN. For significant cancers the ANN was the strongest parameter in DCA. Conclusion The present multicentre study showed that %p2PSA and PHI have a superior diagnostic performance for detecting prostate cancer in the PSA range of 1.6-8.0 ng/mL compared with t-PSA and %f-PSA at initial and repeat biopsy and for predicting significant prostate cancer in men aged ≤65 years. They are equally superior for counselling patients before biopsy. © 2015 BJU International.


PubMed | HIA du Val de Grace, Beckman Coulter, Charité - Medical University of Berlin, Hospital Pontchallou and University of Munster
Type: Journal Article | Journal: BJU international | Year: 2015

To prospectively test the diagnostic accuracy of the percentage of prostate specific antigen (PSA) isoform [-2]proPSA (%p2PSA) and the Prostate Health Index (PHI), and to determine their role for discrimination between significant and insignificant prostate cancer at initial and repeat prostate biopsy in men aged 65 years.The diagnostic performance of %p2PSA and PHI were evaluated in a multicentre study. In all, 769 men aged 65 years scheduled for initial or repeat prostate biopsy were recruited in four sites based on a total PSA (t-PSA) level of 1.6-8.0 ng/mL World Health Organization (WHO) calibrated (2-10 ng/mL Hybritech-calibrated). Serum samples were measured for the concentration of t-PSA, free PSA (f-PSA) and p2PSA with Beckman Coulter immunoassays on Access-2 or DxI800 instruments. PHI was calculated as (p2PSA/f-PSA t-PSA). Uni- and multivariable logistic regression models and an artificial neural network (ANN) were complemented by decision curve analysis (DCA).In univariate analysis %p2PSA and PHI were the best predictors of prostate cancer detection in all patients (area under the curve [AUC] 0.72 and 0.73, respectively), at initial (AUC 0.67 and 0.69) and repeat biopsy (AUC 0.74 and 0.74). t-PSA and %f-PSA performed less accurately for all patients (AUC 0.54 and 0.62). For detection of significant prostate cancer (based on Prostate Cancer Research International Active Surveillance [PRIAS] criteria) the %p2PSA and PHI equally demonstrated best performance (AUC 0.70 and 0.73) compared with t-PSA and %f-PSA (AUC 0.54 and 0.59). In multivariate analysis PHI we added to a base model of age, prostate volume, digital rectal examination, t-PSA and %f-PSA. PHI was strongest in predicting prostate cancer in all patients, at initial and repeat biopsy and for significant prostate cancer (AUC 0.73, 0.68, 0.78 and 0.72, respectively). In DCA for all patients the ANN showed the broadest threshold probability and best net benefit. PHI as single parameter and the base model + PHI were equivalent with threshold probability and net benefit nearing those of the ANN. For significant cancers the ANN was the strongest parameter in DCA.The present multicentre study showed that %p2PSA and PHI have a superior diagnostic performance for detecting prostate cancer in the PSA range of 1.6-8.0 ng/mL compared with t-PSA and %f-PSA at initial and repeat biopsy and for predicting significant prostate cancer in men aged 65 years. They are equally superior for counselling patients before biopsy.


Stephan C.,Charité - Medical University of Berlin | Stephan C.,Urologic | Vincendeau S.,Hospital Pontchaillou | Houlgatte A.,HIA du Val de Grace | And 4 more authors.
Clinical Chemistry | Year: 2013

BACKGROUND: Total prostate-specific antigen (tPSA) is flawed for prostate cancer (PCa) detection. [-2]proprostate-specific antigen (p2PSA), a molecular isoform of free PSA (fPSA), shows higher specificity compared with tPSA or percentage of free PSA (%fPSA). The prostate health index (Phi), a measure based on p2PSA and calculated as p2PSA/fPSA X √tPSA, was evaluated in a multicenter study for detecting PCa. METHODS: A total of 1362 patients from 4 different study sites who had tPSA values of 1.6-8.0 μg/L (668 patients with PCa, 694 without PCa) underwent ≥10 core biopsies. Serum concentrations of tPSA, fPSA (both calibrated against a WHO reference material), and p2PSA were measured on Access2 or DxI800 analyzers (Beckman Coulter). RESULTS: The percentage ratio of p2PSA to fPSA (%p2PSA) and Phi were significantly higher in all PCa subcohorts (positive initial or repeat biopsy result or negative digital rectal examination) (P < 0.0001) compared with patients without PCa. Phi had the largest area under the ROC curve (AUC) (AUC = 0.74) and provided significantly better clinical performance for predicting PCa compared with %p2PSA (AUC = 0.72, P = 0.018), p2PSA (AUC = 0.63, P < 0.0001), %fPSA (AUC = 0.61) or tPSA (AUC = 0.56). Significantly higher median values of Phi were observed for patients with a Gleason score ≥7 (Phi = 60) compared with a Gleason score <7 (Phi = 53; P = 0.0018). The proportion of aggressive PCa (Gleason score ≥7) increased with the Phi score. CONCLUSIONS: The results of this multicenter study show that Phi, compared with tPSA or %fPSA, demonstrated superior clinical performance in detecting PCa at tPSA 1.6-8.0 μg/L (i.e., approximately 2-10 μg/L in traditional calibration) and is better able to detect aggressive PCa. © 2012 American Association for Clinical Chemistry.


PubMed | Impeto Medical, HIA du Val de Grace, University of Paris Descartes and La Pitie Salpetriere Hospital
Type: Journal Article | Journal: Journal of neuro-oncology | Year: 2016

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, potentially severe and dose-limiting adverse effect; however, it is poorly investigated at an early stage due to the lack of a simple assessment tool. As sweat glands are innervated by small autonomic C-fibers, sudomotor function testing has been suggested for early screening of peripheral neuropathy. This study aimed to evaluate Sudoscan, a non-invasive and quantitative method to assess sudomotor function, in the detection and follow-up of CIPN. Eighty-eight patients receiving at least two infusions of Oxaliplatin only (45.4%), Paclitaxel only (14.8%), another drug only (28.4%) or two drugs (11.4%) were enrolled in the study. At each chemotherapy infusion the accumulated dose of chemotherapy was calculated and the Total Neuropathy Score clinical version (TNSc) was carried out. Small fiber neuropathy was assessed using Sudoscan (a 3-min test). The device measures the Electrochemical Skin Conductance (ESC) of the hands and feet expressed in microSiemens (S). For patients receiving Oxaliplatin mean hands ESC changed from 73 2 to 63 2 and feet ESC from 77 2 to 66 3 S (p < 0.001) while TNSc changed from 2.9 0.5 to 4.3 0.4. Similar results were observed in patients receiving Paclitaxel or another neurotoxic chemotherapy. During the follow-up, ESC values of both hands and feet with a corresponding TNSc < 2 were 70 2 and 73 2 S respectively while they were 59 1.4 and 64 1.5 S with a corresponding TNSc 6 (p < 0.0001 and p = 0.0003 respectively). This preliminary study suggests that small fiber neuropathy could be screened and followed using Sudoscan in patients receiving chemotherapy.


Lheureux S.,CLCC Francois Baclesse | Lheureux S.,University of Caen Lower Normandy | Le Moulec S.,HIA du Val de Grace
Bulletin du Cancer | Year: 2011

Apoptosis is a programmed cellular death, a fast process (between four and six hours) in answer to a cellular stress. It involves a sequence of genetically determined intracellular events, allowing the inhibition of the main functions of the cell and its elimination by phagocytosis. The apoptosis inactivation is implied in tumours carcinogenesis. Although the tumour physiopathology implies a defect in activation-induced cell death, the treatment is designed to kill the transformed cells. The aim of this review is to describe the apoptotic mechanisms and to explain the interest of new therapeutic tools targeting apoptosis. Apoptosis is an orderly and synchronized process, regulated by two different pathways, the intrinsic way (mitochondrial) and extrinsic one (the death receptor). The targeting of apoptosis, a pathway intrinsically deficient in the tumor cells, is a potentially interesting strategy when the mechanism of its inhibition is well-identified. Small molecules targeting B-cell leukemia/lymphoma-2 (Bcl-2), inhibitor of apoptosis protein (IAPs) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors are currently under phase I/II studies, which show preliminary efficacy and safety. Their association with standard treatments seems an interesting therapeutic way in order to obtain a synergistic effect on tumor cell death. ©John Libbey Eurotext.


PubMed | Hopital Tenon, HIA du Val de Grace, University of Paris Descartes and University Pierre and Marie Curie
Type: Journal Article | Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine | Year: 2016

The standardized uptake lean body mass (SUL), calculated using lean body mass (LBM), is essential for the semiquantification of (18)F-FDG uptake using PET coupled with CT to avoid a bias linked to the adipose mass. It allows the evaluation of a response to therapy according PERCIST 1.0. The aim of this study was to evaluate the reliability of a method for the estimation of the LBM using the data of the low-dose CT from PET/CT acquired over standard acquisition fields (from skull base to ischia, from vertex to ischia, from skull base to mid thigh, from vertex to mid thigh).We wrote an automated program that determined the LBM from a CT with limited fields of acquisition and applied this method in a large (184 patients) and heterogeneous population. Its results were compared with the measurement of LBM from whole-body CT (reference standard) and the results of 5 predictive equations described in the literature.The results of LBM measurement evaluated with this technique were much closer to the reference standard than those obtained by the mathematic formulas. The intraclass correlations (ICC) of this technique compared with the reference standard were excellent (the best ICC being obtained for the largest acquisition field, from vertex to mid thigh: ICC, 0.994; 95% confidence interval [95% CI], 0.992-0.995; P < 0.0001), much better than the ICC obtained with the mathematic formulas (the best ICC for a mathematic formula was 0.841; 95% CI, 0.714-0.903; P < 0.0001). Moreover, the analysis with the Bland-Altman plot showed that the differences in mean lean masses between the studied technique and the reference standard was the smallest for the proposed technique (for the largest acquisition field, mean difference 0.2 kg with the narrowest 95% CI [-1.8 to 2.2 kg]).This technique could be easily implemented on computers used in practice to allow a more reliable assessment of the SUL in clinical practice notably for the therapeutic evaluations after PERCIST 1.0.


PubMed | Grenoble University Hospital Center and HIA du Val de Grace
Type: Journal Article | Journal: Acta ophthalmologica | Year: 2016

To evaluate the visual field rate of progression of patients with treated ocular hypertension (OHT) and primary open-angle glaucoma (POAG) in clinical practice, using the mean deviation (MD) and the visual field index (VFI).Non-interventional cohort study. From a large multicentre database representative of the French population, 441 eyes of 228 patients with treated OHT or POAG followed up at least 6years with Humphrey 24.2 Sita-Standard visual field examination at least twice a year were identified. From initial data, eyes were classified in five groups: 121 with OHT, 188 with early glaucoma (MD greater than -6dB), 45 with moderate glaucoma (MD -6 to -12dB), 41 with advanced glaucoma (MD -12 to -18dB) and 46 with severe glaucoma (MD less than -18dB). Rate of progression during the follow-up period was calculated using the trend analysis of the Guided Progression Analysis software.The mean duration of follow-up was 8.42.7years and the mean number of visual field, 18.43.5. In eyes with OHT, rate of progression was -0.09dB/year (-0.17%VFI/year). In eyes with POAG, rate of progression was -0.32dB/year (-0.83%VFI/year) in eyes with early glaucoma, -0.52dB/year (-1.81%VFI/year) in moderate glaucoma, -0.54dB/year (-2.35%VFI/year) in advanced glaucoma and -0.45dB/year (-1.97%VFI/year) in severe glaucoma. In eyes with POAG, a significant progression (p<0.05) was detected in 159 of 320 eyes (49.7%) with trend analysis and 117 of 320 eyes (36.6%, likely progression) or 183 of 320 eyes (57.2%, possible and likely progression) with event analysis.Primary open-angle glaucoma is a progressive disease in the majority of patients despite cautioned treatment and follow-up. The rate of progression varies greatly among subjects.


Ramirez C.,Hopital Roger Salengro | Blonski M.,University of Paris 13 | Belin C.,University of Paris 13 | Carpentier A.,University of Paris 13 | Taillia H.,HIA du Val de Grace
Bulletin du Cancer | Year: 2013

The incidence of brain metastases (BM) has increased due to the improvement of therapeutics and diagnostic imaging, but also to an aging population. The initial symptoms may develop suddenly or insidiously over weeks or months. The symptoms depend on the location of the BM and related complications (hydrocephalus, tumor hemorrhage, cerebral herniation). Headaches are the most frequent symptoms (50%); they are related to intracranial hypertension. Cognitive deficits are commonly described at diagnosis (67 to 90.5%). Cognitive assessment is essential because of its impact on patients' prognosis and quality of life. Nevertheless, these deficits remain underestimated. The Karnofsky Perfomance Scale and the Mini Mental State Examination (MMSE) seem inadequate. A short battery was proposed and internationally validated, assessing seven domains: attention (Digit Symbol Test WAIS-III), episodic memory (Hopkins Verbal Learning Test [HVLT]), working memory (Digit Span Test WAIS-III), verbal fluency (Controlled Oral Word Association Test [COWA]), fine motor dexterity (Grooved Pegboard Test), information processing speed (Trail Making Test [TMT] A) and executive functions (TMT B). This battery is relevant, feasible and associated with a good compliance. These cognitive tests are currently recommended to assess cognitive functions in patients with BM. © John Libbey Eurotext.


Guerot F.,HIA du Val de Grace | Saliou H.,HIA du Val de Grace | Lefort H.,Service Medical dUrgence | De Rudnicki S.,HIA du Val de Grace
Soins | Year: 2014

Assigned to French army teaching hospitals, the army nurse can be deployed on overseas operations in support of the armed forces. Experience in the treatment of casualties in life-threatening emergencies is essential, as is the ability to adapt and react. Designated on a voluntary basis, after some two years of working in an army teaching hospital, the hospital nurse receives training in the specificities of the theatre of deployment. © 2014 Elsevier Masson SAS.


Chidiac N.,HIA du Val de Grace
Annales Medico-Psychologiques | Year: 2015

The authors, through various testimonials from writers who almost died during the wars of the twentieth century, show how the psychological trauma and its effects on memory can be elaborated mainly by the work of writing. Writing is perceived as a weaving of the spatio-temporal fracture directly caused by the psychological trauma. © 2015 Elsevier Masson SAS.

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