Adénocarcinomes localement avancés du moyen et du bas rectum après radiochimiothérapie néoadjuvante : étude histopathologique et pronostique de 113 cas

Introduction. La radiochimiothérapie (RCT) néoadjuvante suivie par l’exérèse chirurgicale est le traitement de référence des tumeurs T3-T4 et/ou N+ du bas et du moyen rectum. L’étude histopathologique des pièces opératoires est essentielle dans l’élaboration du pronostic. Objectif Identifier les principaux facteurs histopronostiques dans une série chirurgicale d’adénocarcinomes localement avancés du bas et du moyen rectum après RCT néoadjuvante. Matériels et méthodes. L’analyse de 113 pièces opératoires a été réalisée selon les recommandations du CAP, avec des critères supplémentaires tels que le budding tumoral, la présence de calcifications et la réponse à la RCT néoadjuvante évaluée par le grade de régression tumorale m-RCRG. Résultats. La survie sans récidive à 3 ans était de 67,6%. En analyse univariée, le stade ypTN, le budding, la marge de résection circonférentielle, la positivité des marges et la présence d’emboles vasculaires ou d’engainements péri-nerveux constituaient des facteurs pronostiques. En analyse multivariée, la présence de calcifications et une faible marge de résection circonférentielle étaient des facteurs indépendants prédictifs d’une moins bonne survie. Le grade m-RCRG n’était pas corrélé à la survie sans récidive. Parmi les 50 tumeurs m-RCRG1, la survie sans récidive était meilleure dans le stade ypT0 que dans les autres stades. Conclusion. L’ajout de certains paramètres histologiques, comme la présence d’un budding tumoral, serait intéressant dans le compte-rendu standardisé de résection du rectum après RCT néoadjuvante. Le stade ypT apparaît comme un meilleur facteur prédictif de survie que le grade de régression tumorale

IgA kappa light and heavy chain deposition disease in multiple myeloma

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Malakoplakia as a cause of severe hypercalcemia through ectopic 25-hydroxyvitamin D3 1-alpha-hydroxylase expression

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Renal biopsies should be performed whenever treatment strategies depend on renal involvement

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Critères d’indications de la biopsie rénale chez les patients diabétiques de type 2 protéinuriques : enquête auprès des néphrologues français

National audienceDiabetic nephropathy is usually a presumptive diagnosis based on clinical and biological evidence. Renal biopsies are performed in diabetic patients with atypical findings evoking non-diabetic renal disease who could benefit from specific therapies. French speaking nephrologists were asked which criteria they retain to indicate renal biopsy in patients with type 2 diabetes and albuminuria>0.5g/day or equivalent through an online anonymous questionnaire. Among the suggested criteria were absence of diabetic retinopathy, hematuria, rapid decrease in GFR, short diabetes duration or rapid raise of proteinuria. 188 people answered the poll among whom interns (12%), fellows (13%), university hospital practitioners (26%), general hospital practitioners (24%), practitioners in a non-profit organization (13%), practitioners on private activity (10%), multi-modal practitioners (3%) and people without clinical activity (2%). Increasing proteinuria was retained as an indication criterion for renal biopsy by 51% of respondents, nephrotic syndrome by 56% of respondents, absence of diabetic retinopathy by 57% of respondents, short diabetes duration by 65% of respondents, rapid GFR decline by 75% of respondents and hematuria by 78% of respondents. These data highlight the high diversity of opinions on this topic and their discrepancies with guidelines and current literature regarding the association between non-diabetic renal disease and clinical and biological features. The lack of adhesion of nephrologists to guidelines was especially noteworthy regarding the absence of diabetic retinopathy. These results emphasize the need for studies focusing on biopsy indication criteria in patients with type 2 diabetes

Minimal Change Disease Induced by Lorlatinib

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A CD31-Derived Peptide Prevents the Development of Antibody-Mediated Lesions in a Rat Model of Aortic Allograft

International audienceBackground: Antibody-mediated rejection (AMR) is a major cause of graft loss. The development of donor-specific antibodies (DSAs) directed against the allogeneic HLA molecules expressed by the graft also leads to accelerated arteriosclerosis. CD31 is a protein expressed on endothelial and immune cells, ensuring homeostasis at this interface. When strong immune stimulation occurs, the regulatory function of CD31 is lost owing to cleavage of its extracellular portion. P8RI, a synthetic peptide that binds to the ectodomain of CD31, is able to restore the CD31 immunomodulatory function. In this study, we hypothesized that CD31 could represent an attractive molecular target in AMR and investigated whether P8RI could prevent the development of vascular antibody-mediated lesions. Materials and methods: A rat model of orthotopic aortic allograft was used, and P8RI was administered for 28 days. Circulating DSAs were quantified to assess the alloimmune humoral response, and histologic and immunohistochemical analyses of aortic allografts were performed to estimate antibody-mediated lesions in the allograft. Results: Aorta-allografted rats receiving P8RI developed fewer DSAs than control animals (mean fluorescence intensity 344 vs 741). The density of nuclei in the media (3.4 x 10-5 vs 2.2 x 10-5 nuclei/px2) and media surface area (2.33 x 106 vs 2.02 x 106 px2) were higher in animals treated with P8RI than in control animals. Conclusions: These data support a therapeutic potential for molecules able to restore the CD31 signaling to fight AMR. P8RI, an agonist synthetic peptide targeting CD31, might prevent DSA production and have a beneficial effect in limiting arterial antibody-mediated lesions. CD31 agonists may become therapeutic tools to prevent and treat solid organ transplant arteriosclerosis

HEMATURIA AND ABSENCE OF RETINOPATHY ARE NOT INDICATIVE OF NON -TYPE 2 DIABETES ASSOCIATED RENAL DISEASE IN PATIENTS WITH OTHERWISE TYPICAL DIABETIC KIDNEY DISEASE

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Recruitment of CXCR3+ T cells into injured tissues in adult IgA vasculitis patients correlates with disease activity

International audienceObjectives: Adult immunoglobulin A vasculitis (IgAV) is an immune complex small vessel vasculitis. So far, the involvement of T cells in this pathology has been poorly studied. The aim of this study was to analyze T-cell homeostasis as well as cytokine and chemokine concentrations in the blood and tissues of IgAV patients. Methods: T cells, cytokine and chemokine concentrations were analyzed in peripheral blood using flow cyto-metry and multiplex assays. T-cell infiltrates in the kidney and the skin were characterized by im-munohistochemistry. This study prospectively included 44 adult patients with biopsy-proven IgAV and 24 age-and sex-matched healthy controls.Results: We observed reduced proportions of circulating CXCR5-and CXCR3-expressing memory CD4 T cells at diagnosis but normal values at remission. The plasma levels of Th1-related cytokines (IL-12, IL-27 and IFNγ) and of the TFH-related cytokine, IL-21, were paradoxically not reduced in patients. We observed increased plasma concentrations of the CXCR5 ligand, CXCL13, and of the CXCR3 ligands, CXCL10/11, suggesting a potential relocation of the corresponding T cells into inflamed tissues. We then confirmed the recruitment of CXCR3-expressing T cells into the skin and kidneys. In the skin, T-cell infiltrates mainly co-localized with damaged dermal small vessels. Finally, patients with the largest kidney T-cell infiltrates were also those with the highest proteinuria.Conclusion: Altogether, our results strongly suggest that, in IgAV patients, CXCL10/11 orchestrate the recruitment of CXCR3-expressing T cells in injured tissues, contributing to tissue damage and disease activity

Kidney Biopsy in Type 2 Diabetes: A Multicenter Cross-Sectional Study

International audienceINTRODUCTION: Kidney biopsies (KBs) are performed in patients with type 2 diabetes (T2D) to diagnose non-diabetic or hypertensive kidney disease (NDHKD) potentially requiring specific management compared to diabetic and or hypertensive nephropathy (absence of NDHKD). Indications for KB are based on the presence of atypical features compared to the typical course of diabetic nephropathy. In this study, we assessed the association of different patterns of atypical features, or KB indications, with NDHKD. METHODS: Native KBs performed in patients with T2D were analyzed. Data were collected from the patients’ records. KB indications were determined according to the presence of different atypical features considered sequentially: (1) presence of any feature suggesting NDHKD which is not among the following ones, (2) recent onset of nephrotic syndrome, (3) low or rapidly declining estimated glomerular filtration rate (eGFR), (4) rapid increase in proteinuria, (5) short duration of diabetes, (6) presence of hematuria, or (7) normal retinal examination. RESULTS: Among the 463 KBs analyzed, NDHKD was diagnosed in 40% of the total population and 54, 40, 24, and 7% of the KBs performed for indications 1-4 respectively. Conversely, no patient who underwent KB for indications 5-7 displayed NDHKD. Logistic regression analyses identified eGFRCKD-EPI >15 mL/min/1.73 m2, urinary protein-to-Cr ratio <0.3 g/mmol, hematuria, HbA1c <7%, and diabetes duration <5 years as predictors of NDHKD, independently from the indication group. CONCLUSION: NDHKD is frequent in T2D. Despite the association of hematuria with NDHKD, our results suggest that presence of hematuria and absence of DR are insufficient to indicate KB in the absence of concurrent atypical features. Conversely, rapid progression of proteinuria and rapid deterioration of eGFR are major signals of NDHKD