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Gilard V.,University of Rouen | Alexandru C.,Henri Becquerel Cancer Center | Proust F.,University of Strasbourg | Derrey S.,University of Rouen | And 2 more authors.
Journal of Neuro-Oncology | Year: 2015

Pituitary metastases are uncommon, ranging from 1 to 5 % of all metastases. Between 10 and 30 % of pituitary lesions are symptomatic responsible for diabetes insipidus, visual field defect or cranial nerve palsy. Primary sites are lung or breast in two-thirds of cases. There is no current reference concerning treatment of such lesions. Overall survival is poor and depends on primary site. Although the role of surgery is currently limited, discussion is warranted in several indications for diagnostic or symptomatic purposes. We report two cases of symptomatic pituitary metastases in a context of breast cancer and review the litterature concerning the role of surgery and other treatment modalities. © 2015 Springer Science+Business Media New York Source


Prevost G.,University of Rouen | Ducrotte P.,University of Rouen | Cailleux A.,University of Rouen | Khalfi K.,University of Rouen | And 3 more authors.
Neurogastroenterology and Motility | Year: 2013

Background: Incretin hormones [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)] released by the gut modulate gastrointestinal motility and influence gastric emptying (GE). Abnormal secretion or sensitivity to these hormones could contribute to the pathogenesis of gastroparesis. The aim of this study was to investigate incretin hormone secretion during a prolonged oral glucose load in non-diabetic patients with documented idiopathic gastroparesis. Methods: Fifteen patients referred for digestive postprandial discomfort with delayed GE demonstrated by a 13C-labeled octanoate breath test were included and compared with 10 healthy controls. A 75 g oral glucose load was performed, with blood samplings every 30 min for 5 h, to determine glucose, insulin, GIP, and GLP-1 blood levels. Key Results: Fasting GIP concentration was significantly higher in the patient group (56.1 ± 5.8 pg mL-1 vs 29.9 ± 7.7 pg mL-1, P =0.012). Postglucose load GIP concentrations were also significantly elevated in patients with gastroparesis, whereas GLP-1 concentrations during fasting and postglucose load conditions were not different to those of healthy controls. Moreover, glucose tolerance during glucose load was abnormal in patients, combining hyperglycemic insulin resistance and hyperinsulinism patterns, while fasting values for glycemia, insulin sensitivity, and insulin concentrations were normal. Conclusions & Inferences: Patients with idiopathic gastroparesis exhibit abnormal GIP levels associated with impaired insulin sensitivity during oral glucose load. Further studies are needed to establish the involvement of these defects in the pathophysiology of gastroparesis. © 2013 John Wiley & Sons Ltd. Source


Palie O.,University of Rouen | Michel P.,University of Rouen | Menard J.-F.,University of Rouen | Rousseau C.,Renee Gauducheau Cancer Center | And 15 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2013

Purpose: FDG PET has been suggested to have predictive value in the prognosis of oesophageal carcinoma. However, the retrospective studies reported in the literature have shown discordant results. Additionally, only four studies have evaluated FDG PET during chemoradiotherapy (CRT) in patients with different histological lesions. The purpose of this study was to investigate the predictive value of FDG PET performed early during CRT (on day 21) in a population of patients with oesophageal squamous cell carcinoma. Methods: Included in this prospective study were 57 patients with a histological diagnosis of squamous cell carcinoma of the oesophagus. Of these 57 patients, 48 (84 %) were evaluated (aged 63 ± 11 years; 44 men, 4 women). Each patient underwent FDG PET (4.5 MBq/kg) before CRT, according to the Herskovic protocol (t0; PET1) and on day 21 ± 3 from the start of CRT (d21; PET2). The response assessment included a clinical examination, CT scan or FDG PET and histological analysis 3 months and 1 year after PET 1. The patients were classified as showing a complete response (CR) or a noncomplete response. A quantitative analysis was carried out for PET 1 and PET2 using the following parameters: SUVmax, SUVmean (with SUVmean40 as the 3-D volume at an SUVmax threshold of 40 % and SUVmeanp as that defined by a physician), tumour volume (TV, with TV40 defined as the TV at 40 % of SUVmax, and TVp as that defined by a physician); and the total lesion glycolysis (TLG, SUVmean × TV, with TLG40 defined as the TLG at 40 % of SUVmax, and TLG p as that defined by a physician). The differences in responses at 3 months and 1 year between PET1 (t0) and PET2 (d21) were assessed in terms of variations in SUV, TV and TLG using a repeated measures of variance (ANOVA). Results: SUVmax, SUVmean and TLG decreased significantly between PET1 (t0) and PET2 (d21; p < 0.0001). The TV significantly decreased only when assessed as TVp (p = 0.02); TV 40 did not decrease significantly. With respect to the predictive value of PET1, only TV40-1 and TVp-1 values, and therefore TLG40-1 and TLGp-1, but not the SUV values, were significantly lower in patients with CR at 3 months. SUVmax1, TVp-1 and TLGp-1 were significantly lower in patients with CR at 1 year. With respect to the predictive value of PET2, only TV40-2 and TVp-2 values, and therefore TLG40-2 and TLGp-2, but not the SUV values, were significantly lower in patients with CR at 3 months. None of the PET2 parameters had significant value in predicting patient outcome at 1 year. The changes in SUVmax, TV40, TVp, TLG40 and TLGp between PET1 and PET2 had no relationship to patient outcome at 3 months or 1 year. Conclusion: This prospective, multicentre study performed in a selected population of patients with oesophageal squamous cell cancer demonstrates that the parameters derived from baseline PET1 are good predictors of response to CRT. Specifically, a high TV and TLG are associated with a poor response to CRT at 3 months and 1 year, and a high SUVmax is associated with a poor response to CRT at 1 year. FDG PET performed during CRT on day 21 appears to have less clinical relevance. However, patients with a large functional TV on day 21 of CRT have a poor clinical outcome (ClinicalTrials.gov NCT 00934505). © 2013 Springer-Verlag Berlin Heidelberg. Source


Dupuis J.,Henri Mondor University Hospital | Morschhauser F.,Claude Huriez University Hospital | Ghesquieres H.,Leon Berard Cancer Center | Tilly H.,Henri Becquerel Cancer Center | And 14 more authors.
The Lancet Haematology | Year: 2015

BACKGROUND: Romidepsin is a histone deacetylase inhibitor approved in the USA for patients with recurrent or refractory peripheral T-cell lymphoma and has shown activity in this setting with mainly haematological and gastrointestinal toxicity. Although it has limited efficacy, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used for treatment of de-novo peripheral T-cell lymphoma. We aimed to assess the safety, tolerability, and activity of romidepsin combined with CHOP in patients with previously untreated disease. METHODS: We enrolled patients aged 18-80 years with histologically proven, previously untreated, peripheral T-cell lymphoma (Eastern Cooperative Oncology Group performance status ≤2) into a dose-escalation (phase 1b) and expansion (phase 2) study at nine Lymphoma Study Association centres in France. In the dose-escalation phase, we allocated consecutive blocks of three participants to receive eight 3 week cycles of CHOP (intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [maximum 2 mg] on day 1 and oral prednisone 40 mg/m2 on days 1-5) in association with varying doses of romidepsin. The starting dose was 10 mg/m2 intravenously on days 1 and 8 of each cycle, and we used a 3 + 3 design. We assessed dose-limiting toxicities only during the first two cycles. The primary endpoint was to determine the recommended dose for the combination. For the phase 2 study, we aimed to increase the cohort of patients receiving the recommended dose to a total of 25 patients. Patients were assessed for safety outcomes at least twice per cycle according to the Common Terminology Criteria for Adverse Events, version 4.0. Safety analyses included all patients who received at least one dose of romidepsin and CHOP. This trial is registered at the European Clinical Trials Database (EudraCT), number 2010-020962-91 and ClinicalTrials.gov, number NCT01280526. FINDINGS: Between Jan 13, 2011, and May 21, 2013, we enrolled 37 patients (18 treated in phase 1b and 19 patients in phase 2). Three of six patients initially treated at 10 mg/m2 had a dose-limiting toxicity. The dose-escalation committee decided to modify the study protocol to redefine dose-limiting toxicities with regard to haematological toxicity. Three patients were treated with 8 mg/m2 of romidepsin, an additional three at 10 mg/m2 (one dose-limiting toxicity), and six patients at 12 mg/m2 (three dose-limiting toxicities). We chose romidepsin 12 mg/m2 as the recommended dose for phase 2. Of the 37 patients treated, three had early cardiac events (two myocardial infarctions and one acute cardiac failure). No deaths were attributable to toxicity. 25 (68%) of 37 patients had at least one serious adverse event. Overall, the most frequent serious adverse events were febrile neutropenia (five [14%] of 37 patients), physical health deterioration (five [14%]), lung infection (four [11%]), and vomiting (three [8%]). 33 (89%) of patients had grade 3-4 neutropenia, and 29 (78%) had grade 3-4 thrombocytopenia. INTERPRETATION: Romidepsin can be combined with CHOP but this combination should now be tested in comparison to CHOP alone in a randomised trial. FUNDING: Celgene. © 2015 Elsevier Ltd. All rights reserved. Source


Morisse H.,CNRS Informatics Systems Laboratory | Morisse H.,University of Rouen | Heyman L.,CNRS Informatics Systems Laboratory | Salaun M.,CNRS Informatics Systems Laboratory | And 7 more authors.
Medical Mycology | Year: 2013

The early diagnosis of invasive pulmonary aspergillosis (IPA) is challenging. Fibered confocal fluorescence microscopy (FCFM) is a new technique that allows in vivo imaging of the lung microstructure during bronchoscopy. In this study, we investigated the ability of FCFM to detect a fluorescent peptide-tracer bound to Aspergillus fumigatus in experimental IPA in 13 immunosuppressed, non-neutropenic rats. Subpleural IPA microabscesses were imaged through a transthoracic window using FCFM in vivo after i.v. injection of the c(CGGRLGPFC)-NH2[FITC] peptide (n = 7) or saline. Results were compared to 10 immunosuppressed, non-infected rats and to six immunosuppressed Geosmithia argillacea-infected rats with and without i.v. injection of the peptide. The peptide in vitro specifically labeled A. fumigatus grown under biofilm growth conditions but not G. argillacea. In vivo, FCFM showed a local infiltration of fluorescent host cells in both Aspergillus and Geosmithia infections. Lung/inner thoracic wall fluorescence intensity ratio (FI) did not differ before and after peptide administration on healthy lung areas, on non-specific inflammatory areas, or on Geosmithia micro-abscesses. In contrast, FI increased from 1.05 without peptide to 1.83 after peptide injection on Aspergillus micro-abscesses (p < 0.0001). In peptide-injected rats, FI from IPA foci was higher than from non-specific inflammation or from Geosmithia abscesses (p ≤ 0.002). Using c(CGGRLFPC)-NH2[FITC] peptide, FCFM allows the in vivo specific imaging of pulmonary aspergillosis. These data provide the basis for the in vivo diagnosis of human pulmonary aspergillosis using alveolar confocal endomicroscopy. © 2013 ISHAM. Source

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