Dominique Cazals-Hatem

Identification of Restricted Subsets of Mature microRNA Abnormally Expressed in Inactive Colonic Mucosa of Patients with Inflammatory Bowel Disease

Background Ulcerative Colitis (UC) and Crohns Disease (CD) are two chronic Inflammatory Bowel Diseases (IBD) affecting the intestinal mucosa. Current understanding of IBD pathogenesis points out the interplay of genetic events and environmental cues in the dysregulated immune response. We hypothesized that dysregulated microRNA (miRNA) expression may contribute to IBD pathogenesis. miRNAs are small, non-coding RNAs which prevent protein synthesis through translational suppression or mRNAs degradation, and regulate several physiological processes. Methodology/Findings Expression of mature miRNAs was studied by Q-PCR in inactive colonic mucosa of patients with UC (8), CD (8) and expressed relative to that observed in healthy controls (10). Only miRNAs with highly altered expression (>5 or <0.2 -fold relative to control) were considered when Q-PCR data were analyzed. Two subsets of 14 (UC) and 23 (CD) miRNAs with highly altered expression (5.2->100 -fold and 0.05–0.19 -fold for over- and under- expression, respectively; 0.001<p≤0.05) were identified in quiescent colonic mucosa, 8 being commonly dysregulated in non-inflamed UC and CD (mir-26a,-29a,-29b,-30c,-126*,-127-3p,-196a,-324-3p). Several miRNA genes with dysregulated expression co-localize with acknowledged IBD-susceptibility loci while others, (eg. clustered on 14q32.31), map on chromosomal regions not previously recognized as IBD-susceptibility loci. In addition, in silico clustering analysis identified 5 miRNAs (mir-26a,-29b,-126*,-127-3p,-324-3p) that share coordinated dysregulation of expression both in quiescent and in inflamed colonic mucosa of IBD patients. Six miRNAs displayed significantly distinct alteration of expression in non-inflamed colonic biopsies of UC and CD patients (mir-196b,-199a-3p,-199b-5p,-320a,-150,-223). Conclusions/Significance Our study supports miRNAs as crucial players in the onset and/or relapse of inflammation from quiescent mucosal tissues in IBD patients. It allows speculating a role for miRNAs as contributors to IBD susceptibility and suggests that some of the miRNA with altered expression in the quiescent mucosa of IBD patients may define miRNA signatures for UC and CD and help develop new diagnostic biomarkers.

Which magnetic resonance imaging findings accurately evaluate inflammation in small bowel Crohn's disease? A retrospective comparison with surgical pathologic analysis.

Background: The aim was to evaluate the value of magnetic resonance imaging (MRI) findings in Crohns disease (CD) in correlation with pathological inflammatory score using surgical pathology analysis as a reference method. Methods: CD patients who were to undergo bowel resection surgery underwent MR enterography before surgery. The CD pathological inflammatory score of the surgical specimens was classified into three grades: mild or nonactive CD, moderately active CD, and severely active CD; fibrosis was also classified into three grades: mild, moderate, and severe. Mural and extramural MRI findings were correlated with pathological inflammatory and fibrosis grades. Results: Fifty‐three consecutive patients were included retrospectively. The mean delay between MRI and surgery was 24 days (range 1–90, median 14). The CD pathological inflammatory score was graded as follows: grade 0 (11 patients, 21%), grade 1 (15 patients, 28%), and grade 2 (27 patients, 51%). MRI findings significantly associated with pathological inflammatory grading were wall thickness (P < 0.0001), degree of wall enhancement on delayed phase (P < 0.0001), pattern of enhancement on both parenchymatous (P = 0.02), and delayed phase, (P = 0.008), T2 relative hypersignal wall (P < 0.0001), blurred wall enhancement (P = 0.018), comb sign (P = 0.004), fistula (P < 0.0001), and abscess (P = 0.049). The inflammation score correlated with the fibrosis score (r = 0.63, P = 0.0001). Conclusions: Our study identified MRI findings significantly associated with surgical pathological inflammation. These lesions are considered potentially reversible and may be efficiently treated medically. We also showed that fibrosis was closely and positively related to inflammation. Inflamm Bowel Dis 2011

Hepatocellular-cholangiocarcinoma: helical computed tomography findings in 30 patients.

Objective To report the helical multiphasic computed tomography (CT) findings in 30 patients with hepatocellular-cholangiocarcinoma. Method We evaluated age, gender, tumor risk factors, serum tumor markers, symptoms, and tumor morphology and enhancement on helical multiphasic CT in 30 patients. Results Twenty-six of 30 patients (86%) were men. Patients had an age range of 27–78 years (mean = 58 years). Abdominal signs or symptoms were present in 21 of 30 patients, and 25 of 30 (83%) had chronic liver disease. Helical CT demonstrated a well-defined tumor in all patients with signs of malignancy such as hepatic hypervascularity (63%), biliary obstruction (17%), satellite lesions (40%), and lymphadenopathy (27%). Portions of the tumor were hyperattenuated on arterial-phase imaging and hypoattenuated on all other phases, whereas other portions showed delayed persistent enhancement, sometimes (27%) with hepatic capsular retraction, findings that have been reported to be characteristic of hepatocellular carcinoma and cholangiocarcinoma, respectively. Conclusion The diagnosis of hepatocellular-cholangiocarcinoma should be considered when a hepatic tumor has CT features of both hepatocellular carcinoma and cholangiocarcinoma. Radiologists should be aware of this tumor type so that the biopsy is performed properly to allow sufficient tissue sampling.

The significance of nonobstructive sinusoidal dilatation of the liver: Impaired portal perfusion or inflammatory reaction syndrome.

Sinusoidal dilatation found in the absence of an impaired sinusoidal blood outflow has been so far of unclear significance. Sinusoidal dilatation may actually be a nonspecific feature of impaired portal venous blood inflow, whatever the cause, or a feature of severe systemic inflammatory reaction syndrome, whatever the cause. Sinusoidal dilatation is mainly located in the centrilobular area even in the absence of an outflow block. A predominantly periportal location is specifically found in oral contraceptive users, associated with an inflammatory condition. There is strong evidence for the association of sinusoidal dilatation and oxaliplatin‐based chemotherapy but not for estroprogestative steroids or thiopurine derivatives. Exposure to anabolic androgen steroids appears to cause sinusoidal changes different from a mere sinusoidal dilatation. Conclusion: There is evidence of activation of the interleukin‐6 and vascular endothelial growth factor pathways in sinusoidal dilatation, but the mechanisms linking the activation of these pathways with the microvascular changes must be identified. (Hepatology 2015;62:956–963)

Tumeur à cellules géantes ostéoclastiques du pancréas

Resume Les tumeurs a cellules geantes osteoclastiques sont des tumeurs osseuses de l’adulte considerees comme benignes selon l’OMS mais localement agressives. Des tumeurs strictement identiques sont decrites dans le pancreas sans localisation osseuse concomitante. Nous rapportons l’observation d’une femme de 62 ans ayant une tumeur a cellules geantes osteoclastiques du pancreas gauche, sans contingent epithelial identifiable, dont le diagnostic n’a ete fait qu’apres exerese, et sans recidive avec un recul de 24 mois. Ces tumeurs pancreatiques sont exceptionnelles, d’histogenese imprecise et souvent confondues avec les carcinomes pleomorphes ou indifferencies pancreatiques avec composante a cellules geantes osteoclastiques, de pronostic tres sombre. Ces tumeurs pancreatiques a cellules geantes osteoclastiques se presentent comme de volumineuses formations kystiques. L’exerese chirurgicale complete assure dans certains cas une survie prolongee.

Quantitative MRI in murine radiation-induced rectocolitis: comparison with histopathological inflammation score

Murine radiation‐induced rectocolitis is considered to be a relevant animal model of gastrointestinal inflammation. The purpose of our study was to compare quantitative MRI and histopathological features in this gastrointestinal inflammation model.