LYMPHOMES T/NK NASAL ET DE TYPE NASAL (ETUDE DE 15 CAS ; ANALYSE EN IMMUNOHISTOCHIMIE DE PARAMETRES POTENTIELS DE CHIMIORESISTANCE)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

A virtual liver biopsy based on mixed MRI radiomics and biological data: a proof of concept

International audienceWhereas NASH is associated with poor long-term outcome, widespread screening is not currently feasible given that a definitive diagnosis of NASH can only be made through liver biopsy. In this study, a virtual liver biopsy was developed with machine learning from mixed multiparametric MRI radiomics and biological data

Computer-assisted topological analysis of renal allograft inflammation adds to risk evaluation at diagnosis of humoral rejection

International audienceAntibody-mediated rejection is associated with heterogeneous kidney allograft outcomes. Accurate evaluation of risk for graft loss at time of diagnosis is necessary to offer personalized treatment. In contrast with serological and molecular assessment, morpho-histological evaluation of antibody-mediated rejection lesions has not significantly evolved. This relies on Banff classifications designed to be of diagnostic discriminatory power rather than prognostic and face quantitative and qualitative limitations. Here we developed a method of Computer-assisted Analysis of Graft Inflammation (CAGI) to improve the classification of allograft inflammation. Digitization of immunostained biopsy sections, image processing and algorithm-driven analysis allowed quantification of macrophages, T cells, B cells, and granulocytes per unit surface of interstitium, capillaries or glomeruli. CAGI was performed on biopsy specimens of 52 patients with extensively phenotyped antibody-mediated rejection. Macrophage numbers in capillaries and interstitium, but not Banff scores or the amount of other immune cell subsets, correlated with donor-specific antibody (DSA) mean fluorescence intensity and DSA-C3d status. The quantity of macrophages in the interstitium and DSA-C3d status were the only independent predictors for significant allograft loss at the time of antibody-mediated rejection diagnosis (hazard ratio 3.71 and 2.34, respectively). A significant strategy integrating the DSA-C3d assay and the quantification of interstitial macrophages allowed identification of three groups with distinct renal prognosis: DSA-C3d-, DSA-C3d+/macrophages-low and DSAC3d+/macrophages-high. Thus, CAGI brings a missing piece to the antibody-mediated rejection puzzle by identifying morpho-histological processes that bridge in~vitro parameters of DSA pathogenicity and graft loss. Hence, this approach could be useful in future integrated strategies of risk evaluation

Histological features of liver disease development in the Atp7b −/− mouse: a model of Wilson’s disease

International audienceAims Wilson’s disease (WD) is caused by mutations in the ATP7B gene, resulting in copper accumulation and toxicity in liver and brain tissues. Due to the initial asymptomatic liver involvement, the progression of liver injuries in WD stays primarily unknown. Atp7b−/− knockout mice have been shown to be an appropriate model of WD for liver involvement. Methods A total of 138 Atp7b−/− mice were included and separated into five groups according to age as follows: 6, 20, 39 and 50 weeks without treatment, and 50 weeks with copper chelator treatment from 39 to 50 weeks of age and compared with 101 wild-type (WT) mice at the same stages. The evolution of histological liver lesions was analysed and compared between groups. Results Significant changes were observed in Atp7b−/− mice compared with WT. Copper deposits in hepatocytes appeared as early as 6 weeks but no significant increase over time was observed. Inflammation appeared as early as 6 weeks and progressed henceforth. Lobular and periportal acidophilic bodies appeared after 20 weeks. Significant atypia was also observed at 20 weeks and increased over time to reach a severe stage at 39 weeks. Fibrosis also became apparent at 20 weeks, progressing subsequently to precirrhotic stages at 50 weeks. Copper content, inflammation and fibrosis scores were significantly reduced in the treated group. No bile duct lesions or dysplastic changes were noted. Conclusions Copper accumulation leads to progressive changes in Atp7b−/− mice regarding inflammation, fibrosis and atypia. The severity of liver damage is lessened by chelation therapy

Gemcitabine and oxaliplatin combination chemotherapy for metastatic well-differentiated neuroendocrine carcinomas: a single-center experience.

International audienceBACKGROUND:: Beyond the usual regimens based on streptozocin and doxorubicin or 5-fluorouracil, no second-line therapy of metastatic neuroendocrine tumor has gained wide acceptance. Gemcitabine and oxaliplatin are generally well tolerated and have shown activity against a wide range of malignancies. The authors assessed the efficacy of gemcitabine-oxaliplatin combination (GEMOX) in the treatment of patients with metastatic neuroendocrine tumors. METHODS:: Twenty consecutive patients with progressive disease were treated with GEMOX, in most cases after failure of other chemotherapy regimens (median = 2). Patients were followed for evidence of toxicity, response, and survival. Two patients were chemotherapy-naive at treatment initiation and were excluded from the efficacy analysis. RESULTS:: Toxicity was manageable overall; however, 6 (30%) patients had to discontinue treatment because of oxaliplatin-induced neurotoxicity (grade 2). Three (17%) of 18 patients had a partial response, median progression-free survival was 7.0 months, and median overall survival was 23.4 months. CONCLUSIONS:: Gemcitabine-oxaliplatin combination shows interesting activity and is well tolerated in pretreated patients with neuroendocrine tumors. Cancer 2009. (c) 2009 American Cancer Society

Metabolomics of Small Intestine Neuroendocrine Tumors and Related Hepatic Metastases

International audienceTo assess the metabolomic fingerprint of small intestine neuroendocrine tumors (SI-NETs) and related hepatic metastases, and to investigate the influence of the hepatic environment on SI-NETs metabolome. Ninety-four tissue samples, including 46 SI-NETs, 18 hepatic NET metastases and 30 normal SI and liver samples, were analyzed using 1H-magic angle spinning (HRMAS) NMR nuclear magnetic resonance (NMR) spectroscopy. Twenty-seven metabolites were identified and quantified. Differences between primary NETs vs. normal SI and primary NETs vs. hepatic metastases, were assessed. Network analysis was performed according to several clinical and pathological features. Succinate, glutathion, taurine, myoinositol and glycerophosphocholine characterized NETs. Normal SI specimens showed higher levels of alanine, creatine, ethanolamine and aspartate. PLS-DA revealed a continuum-like distribution among normal SI, G1-SI-NETs and G2-SI-NETs. The G2-SI-NET distribution was closer and clearly separated from normal SI tissue. Lower concentration of glucose, serine and glycine, and increased levels of choline-containing compounds, taurine, lactate and alanine, were found in SI-NETs with more aggressive tumors. Higher abundance of acetate, succinate, choline, phosphocholine, taurine, lactate and aspartate discriminated liver metastases from normal hepatic parenchyma. Higher levels of alanine, ethanolamine, glycerophosphocholine and glucose was found in hepatic metastases than in primary SI-NETs. The present work gives for the first time a snapshot of the metabolomic characteristics of SI-NETs, suggesting the existence of complex metabolic reality, maybe characteristic of different tumor evolution

Current Management and Predictive Factors of Lymph Node Metastasis of Appendix Neuroendocrine Tumors : A National Study from the French Group of Endocrine Tumors (GTE)

International audienceOBJECTIVE:The primary endpoint was to analyze the predictive factors of lymph node involvement (LN+).BACKGROUND:Indications for additional right hemicolectomy (RHC) with lymph node (LN) resection after appendectomy for appendix neuroendocrine tumor (A-NET) remain controversial, especially for tumors between 1 and 2 cm in size.METHODS:National study including all patients with nonmetastatic A-NET diagnosed after January, 2010 in France.RESULTS:In all, 403 patients were included. A-NETs were: within tip (67%), body (24%) or base (9%) of the appendix; tumor size was 2 cm (8%); grade 1 (91%); mesoappendix involvement 3 mm (5%); lymphovascular (15%) or perineural (24%) invasion; and positive resection margin (8%). According to the European NeuroEndocrine Tumor Society (ENETS) recommendations, 85 patients (21%) should have undergone RHC. The agreement between ENETS guidelines and the multidisciplinary tumor board for complementary RHC was 89%. In all, 100 (25%) patients underwent RHC with LN resection, 26 of whom had LN+. Tumor size (best cut-off at 1.95 cm), lymphovascular and perineural invasion, and pT classifications were associated with LN+. Among the 44 patients who underwent RHC for a tumor of 1 to 2 cm in size, 8 (18%) had LN+. No predictive factor of LN+ (base, resection margins, grade, mesoappendix, lymphovascular, perineural involvement) was found in this subgroup of patients.CONCLUSIONS:In the largest study using the latest pathological criteria for completion RHC in A-NET, a quarter of patients had residual tumor. Further studies are warranted to demonstrate the survival impact of RHC in this setting

Stromal protein βig-h3 reprogrammes tumour microenvironment in pancreatic cancer

International audiencePancreatic cancer is associated with an abundant stromal reaction leading to immune escape and tumour growth. This massive stroma drives the immune escape in the tumour. We aimed to study the impact of βig-h3 stromal protein in the modulation of the antitumoural immune response in pancreatic cancer