Jean Francois Mosnier

Expression of cytokine-dependent immune adhesion molecules by hepatocytes and bile duct cells in chronic hepatitis C

BACKGROUND/AIMS The pathogenesis of liver cell injury in chronic hepatitis C is poorly understood. To test whether immune-mediated mechanisms might be involved in the pathogenesis of liver cell injury during infection by hepatitis C virus, the expression of cytokine-dependent immune molecules by hepatocytes and bile duct cells during chronic hepatitis C was studied. METHODS In 35 patients, expression of class I and II HLA antigens, intercellular adhesion molecule (ICAM) 1, and lymphocyte function antigen (LFA) 3 was studied by immunohistochemistry and scored by a semiquantitative grading system. Statistical analysis was performed using Spearmans test and t test. RESULTS Class I HLA antigens were induced on hepatocytes in 20 cases. In all cases, HLA-DR, ICAM-1, and/or LFA-3 were detected on hepatocytes in piecemeal necrosis and intralobular clusters. Bile duct cells expressed HLA-DR in 32 cases and ICAM-1 and LFA-3 in 14 cases. Expression levels of immune molecules on hepatocytes correlated with aminotransferase activity (P < 0.035), histological activity (P < 0.001), and score of necrosis (P < 0.01). ICAM-1 expression on hepatocytes was higher in patients with intraportal lymphoid nodules (P = 0.005). Expression levels of ICAM-1 and LFA-3 on bile ducts correlated with the severity of bile duct damage (P < 0.015). CONCLUSIONS These results suggest the involvement of immune-mediated mechanisms in the pathogenesis of liver cell injury in chronic hepatitis C.

Pathology Analysis Reveals That Dysplastic Pancreatic Ductal Lesions Are Frequent in Patients With Hereditary Pancreatitis

BACKGROUND & AIMS Hereditary pancreatitis (HP) is a risk factor for pancreatic adenocarcinoma. We performed a retrospective, multicenter study to characterize and evaluate the frequency of pancreatic intraepithelial neoplasia (PanIN) and to describe the characteristics of fibrosis in pancreatic surgical specimens from patients with HP. METHODS Samples from partial pancreatectomies (n = 13) of patients with HP complications (n = 12; 7 males; mean age, 24 y; 1 patient underwent 2 surgeries over 16 years) were analyzed by histologic and immunohistologic analyses; patients with suspected or proven pancreatic adenocarcinoma were excluded. HP diagnosis was confirmed by analysis of PRSS1 mutations. Dysplastic lesions were described according to the PanIN classification. RESULTS Eleven patients were found to have the R122H mutation in PRSS1 and 1 patient was found to have the N29I mutation in PRSS1. Fifty-one PanIN lesions were observed in 10 specimens (77%): PanIN lesions 1a, 1b, 2, and 3 were observed in 8, 5, 8, and 5 specimens, respectively. The median number of PanIN lesions was 3.5 for each specimen. The density of the lesions was 2.6 per 10 cm(2). The size of lesions was greater than 0.5 mm in 55% of the samples. Two patients with PanIN-3 developed pancreatic cancer, 18 months and 44 years after surgery. CONCLUSIONS PanIN lesions are frequent, severe, and occur early in the course of HP. Among patients with PanINs, 50% had PanIN-3 lesions. Pancreatectomy could be considered as a prophylactic against pancreatic cancer in patients with high-grade dysplasia.

Abcès cérébraux multiples à Actinomyces

Resume Introduction L’actinomycose est une infection bacterienne subaigue ou chronique qui atteint le sujet aussi bien immunocompetent qu’immunodeprime. Les lesions cervico-faciales et thoraco-abdominales sont les plus frequentes. Les localisations cerebrales sont exceptionnelles mais de pronostic severe. Observation Une femme de 56 ans, immunocompetente, etait hospitalisee pour un tableau infectieux non documente avec troubles du comportement et desorientation temporo-spatiale. Une aggravation progressive des signes neurologiques conduisait au coma avec necessite de ventilation mecanique. La neuro-imagerie montrait des abces cerebraux multiples dont la biopsie stereotaxique neurochirurgicale permettait le diagnostic anatomo-pathologique d’actinomycose. Un traitement adapte par bi-antibiotherapie et sans exerese chirurgicale permettait une evolution clinique favorable. Commentaires En l’absence de documentation microbiologique, l’examen histologique permet le diagnostic d’actinomycose cerebrale. Une double antibiotherapie adaptee peut permettre la guerison sans sequelle, meme en presence d’abces cerebraux multiples.