A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer

<p>Abstract</p> <p>Background</p> <p>The distinction between primary and secondary ovarian tumors may be challenging for pathologists. The purpose of the present work was to develop genomic and transcriptomic tools to further refine the pathological diagnosis of ovarian tumors after a previous history of breast cancer.</p> <p>Methods</p> <p>Sixteen paired breast-ovary tumors from patients with a former diagnosis of breast cancer were collected. The genomic profiles of paired tumors were analyzed using the Affymetrix GeneChip^®Mapping 50 K Xba Array or Genome-Wide Human SNP Array 6.0 (for one pair), and the data were normalized with ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) algorithm or Partek Genomic Suite, respectively. The transcriptome of paired samples was analyzed using Affymetrix GeneChip^®Human Genome U133 Plus 2.0 Arrays, and the data were normalized with gc-Robust Multi-array Average (gcRMA) algorithm. A hierarchical clustering of these samples was performed, combined with a dataset of well-identified primary and secondary ovarian tumors.</p> <p>Results</p> <p>In 12 of the 16 paired tumors analyzed, the comparison of genomic profiles confirmed the pathological diagnosis of primary ovarian tumor (n = 5) or metastasis of breast cancer (n = 7). Among four cases with uncertain pathological diagnosis, genomic profiles were clearly distinct between the ovarian and breast tumors in two pairs, thus indicating primary ovarian carcinomas, and showed common patterns in the two others, indicating metastases from breast cancer. In all pairs, the result of the transcriptomic analysis was concordant with that of the genomic analysis.</p> <p>Conclusions</p> <p>In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors. Transcriptomic analysis may be used when primary breast tissue specimen is not available.</p

Gastrostomie percutanée endoscopique ou radiologique dans la sclérose latérale amyotrophique (Analyse multivariée d'efficacité, de tolérance et de survie)

ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Performance diagnostique des signes échographiques dans le diagnostic de fibrose sévère

Introduction : Les patients ayant une fibrose sévère doivent être détectés précocement afin de prévenir les complications telles que la rupture de varices ou le carcinome hépatocellulaire .L échographie largement utilisée pour des symptômes variés, pourrait permettre de détecter ces patients. Néanmoins pour atteindre ce but, les signes échographiques faisant suspecter la présence d une fibrose sévère doivent être simples et faciles à rechercher. Objectif : Le but de l'étude était de sélectionner et de valider dans une population de patients asymptomatiques suivie pour une hépatopathie chronique, les paramètres les plus performants dans la prédiction d'une fibrose sévère F>=3 et de proposer un algorithme permettant de spécifier les patients qui nécessiteront d'autres investigations.Méthode : Etude prospective de décembre 2001 à décembre 2009, incluant des patients asymptomatiques suivis pour une hépatopathie chronique. 7 paramètres échographiques ont été évalués. Résultats : Dans notre étude, la surface irrégulière du foie, la longueur de la rate et l altération du spectre des veines sus hépatiques, apparaissent répondre à notre étude et mériteraient d être validés dans la population générale.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Comment quantifier la stéatose hépatique ?

International audienceThe frequency of hepatic steatosis in the population and its potential complications require knowing how to diagnose and quantify this lesion in clinical practice. Ultrasound allows semi-quantification based on the liver/kidney signal ratio. The CT scanner has a marginal rule, mainly before surgery of resection and before transplantation. MRI is the technique of choice for quantification, using simple multi-echo techniques and manufacturer or free softwares like MRQuantif. The quantification of steatosis in MRI should always be associated with iron quantification to avoid errors. The discovery of steatosis must systematically lead to the search for hepatic fibrosis, at best at the same time using ultrasonore elastometry. Incidental finding of steatosis must be semi-quantified and noted in the report. The indications to look after hepatic steatosis are the existence of liver biological abnormalities, obesity, type 2 diabetes, metabolic syndrome or the existence of cardiovascular risks. In this situation, ultrasound technic is recommended for the evaluation of steatosis. When accurate quantification of steatosis is required, the currently recommended tool is MRI with the multi-echo technique.La fréquence de la stéatose hépatique et ses complications potentielles imposent de savoir diagnostiquer et quantifier cette lésion au quotidien. L’échographie permet une semi-quantification en se basant sur le rapport de signal foie/rein. Le scanner à une place marginale principalement avant chirurgie et avant transplantation dans les bilans des donneurs potentiels. L’IRM est l’examen de quantification, par le biais des techniques simples multiéchos et les logiciels constructeurs ou publics type MRQuantif. La quantification de la stéatose en IRM doit toujours être associée à celle du fer pour éviter les erreurs de quantification. La découverte d’une stéatose doit entraîner systématiquement la recherche d’une fibrose hépatique, au mieux dans le même temps en utilisant les outils d’élastométrie ultrasonore. Outre, la découverte fortuite qui doit être semi-quantifiée et notée dans le compte rendu, les indications de diagnostic de stéatose hépatique sont l’existence de perturbations du bilan biologique hépatique, d’une obésité, d’un diabète de type 2, d’un syndrome métabolique ou de risques cardiovasculaires. Dans cette situation, l’échographie est l’examen recommandé pour l’évaluation de la stéatose. Lorsqu’une quantification précise de la stéatose est nécessaire, l’outil actuellement recommandé est l’IRM avec la technique multiéchos

Imaging after percutaneous thermal and non-thermal ablation of hepatic tumour: normal appearances, progression and complications

International audienceThe increasing number of liver tumours treated by percutaneous ablation leads all radiologists to be confronted with the difficult interpretation of post-ablation imaging. Radiofrequency and microwave techniques are most commonly used. Recently, irreversible electroporation treatments that do not induce coagulation necrosis but cellular apoptose and respect the collagen architecture of bile ducts and vessels have been introduced and lead to specific post-ablation features and evolution. Ablations cause ‘normal’ changes in ablation and periablation zones. It is necessary to know these post-ablation features to avoid the misinterpretation of recurrence or complication that would lead to unnecessary treatments. Another challenge for the radiologist is to detect as early as possible the residual unablated tumour or the disease progression (local progression and tumour seeding) that will require a new treatment. Finally, the complications, frequent or rarer, should be recognised to be managed adequately. The purpose of this article is therefore to describe the large spectrum of normal and pathological aspects related to the treatment of hepatic tumour by percutaneous thermal ablation and irreversible electroporation ablation

A novel mutation in the NR3C1 gene associated with reversible glucocorticoid resistance: Reversible glucocorticoid resistance: case report

International audienceAbstract Objective Glucocorticoid resistance is a rare endocrine disease caused by variants of the NR3C1 gene encoding the glucocorticoid receptor (GR). We identified a novel heterozygous variant (GR R569Q) in a patient with uncommon reversible glucocorticoid resistance syndrome. Methods We performed ex vivo functional characterization of the variant in patient fibroblasts and in vitro through transient transfection in undifferentiated HEK 293T cells to assess transcriptional activity, affinity, and nuclear translocation. We studied the impact of the variant on the tertiary structure of the ligand-binding domain through 3D modeling. Results The patient presented initially with an adrenal adenoma with mild autonomous cortisol secretion and undetectable adrenocorticotropin hormone (ACTH) levels. Six months after surgery, biological investigations showed elevated cortisol and ACTH (urinary free cortisol 114 µg/24 h, ACTH 10.9 pmol/L) without clinical symptoms, evoking glucocorticoid resistance syndrome. Functional characterization of the GRR569Q showed decreased expression of target genes (in response to 100 nM cortisol: SGK1 control +97% vs patient +20%, P &lt; .0001) and impaired nuclear translocation in patient fibroblasts compared to control. Similar observations were made in transiently transfected cells, but higher cortisol concentrations overcame glucocorticoid resistance. GR R569Q showed lower ligand affinity (Kd GRWT: 1.73 nM vs GR R569Q: 4.61 nM). Tertiary structure modeling suggested a loss of hydrogen bonds between H3 and the H1–H3 loop. Conclusion This is the first description of a reversible glucocorticoid resistance syndrome with effective negative feedback on corticotroph cells regarding increased plasma cortisol concentrations due to the development of mild autonomous cortisol secretion

Cystic liver lesions: a pictorial review

International audienceAbstract Hepatic cysts (HC) are sac-like structures mainly filled with liquid and showing a distinct membrane. They are usually found incidentally through imaging. A wide spectrum of imaging patterns may be observed for common and uncommon, neoplastic and non-neoplastic diseases. While simple hepatic cysts occur frequently and do not require any treatment or follow-up, non-typical cysts should be carefully analysed to avoid misdiagnosing a lesion that would require appropriate management. Therefore, adequate knowledge of all the relevant imaging patterns is critical to secure an accurate diagnosis. The aim of this review is to describe the imaging features of the different types of hepatic cysts

Intraoperative Contrast-Enhanced Ultrasound in Colorectal Liver Metastasis Surgery Improves the Identification and Characterization of Nodules

International audienceINTRODUCTION: The sensitivity of preoperative assessment of colorectal liver metastases (CRLM) ranges from 74 to 80%. Intraoperative ultrasound (IOUS) associated with contrast-enhanced intraoperative ultrasound (CE-IOUS) may be able to improve this. Thus, the aims of this study were to assess the value of IOUS and CE-IOUS for the surgical approach and to determine risk factors both for the detection of new nodules and for the modification of the surgical strategy.MATERIALS AND METHODS: Forty-three patients who underwent CRLM surgery were included. These patients had an MRI in the 8 weeks preceding surgery and benefited from intraoperative IOUS and CE-IOUS.RESULTS AND DISCUSSION: The use of IOUS/CE-IOUS permitted the identification of 43 additional lesions and an improved characterization of nodules in 23 patients with a resulting modification of surgical strategy. Lesions were down-staged in six patients and up-staged in six patients. Chemotherapy (p = 0.02) and the presence of nodules in the left lobe (p = 0.04) were predictive factors for finding new nodules at IOUS/CE-IOUS. The discovery of a new nodule systematically modified surgical management. IOUS/CE-IOUS improved intraoperative management of liver metastases. The techniques enable pertinent modification of surgical resections and a reduction of residual lesions.</p