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Pierre Bedossa

Publications and source records attributed to Pierre Bedossa.

50 records · Page 3Linked to original sources
PubMed2003

[Clinical practice guidelines: Standards, Options and Recommendations for the diagnosis of carcinomas of unknown primary site].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To define Clinical Practice Guidelines (CPG) for the diagnosis of carcinomas of unknown primary site. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: The main recommendations for the diagnosis of carcinomas of unknown primary site are: 1) Diagnostic strategy should aim to identify anatomoclinical entities of carcinomas of unknown primary site for which there is a specific treatment. For other anatomoclinical entities, identification of the primary tumour has no impact on the prognostic or therapeutic consequences, thus a systematic complete assessment is unnecessary. 2) An immunohistochemical investigation for the diagnosis should be performed using an appropriate panel of specific antibodies. This should enable the diagnosis of lymphoma, melanoma, germ cell tumour and sarcoma to be eliminated and the diagnosis of prostate, breast, ovary, thyroid or neuroendocrine tumours to be positively identified. 3) A sample can be frozen to enable typing, cytogenetic and, particularly, molecular biological studies to be performed later. 4) The clinician and pathologist should compare their opinions before and after the pathological diagnosis.

Humans↗
PubMed2002

Solid adenoma with exclusive hepatocellular differentiation: a new variant among pancreatic benign neoplasms?

We report a unique, previously unreported pancreatic tumor with hepatoid differentiation associated with serous microcystic adenoma in a 70-year-old man. These two lesions localized, respectively, at the body and the tail of the pancreas, were found incidentally on abdominal ultrasonography. Serum alpha-fetoprotein was not increased and no hepatic lesion was displayed on computed tomography. A subtotal pancreatectomy with splenectomy was performed. The patient is alive and well 12 months after resection. Pathological examination showed a very unusual encapsulated solid tumor with hepatocytic differentiation, bile production and immunoreactivity for hepatocyte paraffin-1 antibody. The tumor cells were negative for endocrine (neuron-specific enolase, chromogranin A, synaptophysin) and acinar (amylase, trypsin) markers. Ultrastructurally, zymogen and neurosecretory granules were absent. The features of the tumor were almost indistinguishable from those of hepatocellular adenoma; therefore, we believe that this solid hepatoid tumor may represent a variant of pancreatic adenoma. Recognition of this entity is important because the only reported pancreatic hepatoid tumors to date have been malignant. The main differential diagnoses include hepatoid ductal adenocarcinoma, hepatoid acinar cell carcinoma, primitive hepatoid endocrine tumor, and metastatic hepatocellular carcinoma.

Adenoma↗
PubMed2002

Genetic analysis of autoimmune sialadenitis in nonobese diabetic mice: a major susceptibility region on chromosome 1.

The nonobese diabetic (NOD) mouse strain provides a good study model for Sjögren's syndrome (SS). The genetic control of SS was investigated in this model using different matings, including a (NOD x C57BL/6 (B6))F(2) cross, a (NOD x NZW)F(2) cross, and ((NOD x B6) x NOD) backcross. Multiple and different loci were detected depending on parent strain combination and sex. Despite significant complexity, two main features were prominent. First, the middle region of chromosome 1 (chr.1) was detected in all crosses. Its effect was most visible in the (NOD x B6)F(2) cross and dominated over that of other loci, including those mapping on chr.8, 9, 10, and 16; the effect of these minor loci was observed only in the absence of the NOD haplotype on chr.1. Most critically, the chr.1 region was sufficient to trigger an SS-like inflammatory infiltrate of salivary glands as shown by the study of a new C57BL/6 congenic strain carrying a restricted segment derived from NOD chr.1. Second, several chromosomal regions were previously associated with NOD autoimmune phenotypes, including Iddm (chr.1, 2, 3, 9, and 17, corresponding to Idd5, Idd13, Idd3, Idd2, and Idd1, respectively), accounting for the strong linkage previously reported between insulitis and sialitis, and autoantibody production (chr.10 and 16, corresponding to Bana2 and Bah2, respectively). Interestingly, only two loci were detected in the (NOD x NZW)F(2) cross, on chr.1 in females and on chr.7 in males, probably because of the latent autoimmune predisposition of the NZW strain. Altogether these findings reflect the complexity and heterogeneity of human SS.

Animals↗
PubMed2002

Impact of different combined preservation modalities on warm ischemic kidneys: effect on oxidative stress, hydrostatic perfusion characteristics and tissue damage.

Hemodynamic disorders in brain dead organ donors induce hypoxia, warm ischemia and finally tissue damage. A cold preservation period also induces tissue and cellular lesions. The two major modes of preservation are cold storage (CS) and hypothermic pulsatile perfusion (HPP). We aimed to compare the influence of each mode of preservation and their combination on oxidative stress, perfusion characteristics and tissue damage, after a period of warm ischemia. Rat kidneys which had undergone ischemia (0, 30, 60 min) were preserved either by CS (12, 24 h), or by HPP (12 h), or by a combination of both (HPP+CS, CS+HPP), in University of Wisconsin cold storage solution (UWCSS) at + 4 degrees C. During HPP, renal vascular pressure decreased then increased to reach 90 mmHg after perfusion for 7 h. If HPP followed CS, the mean pressure reached 200 mmHg, showing successive high amplitude peaks. HPP had a deleterious effects on tissue structure with tubular necrosis, and induced an increase in catalase (Cat) and a decrease in manganese superoxide dismutase (Mn SOD) and gluthatione peroxidase (GPx) activity. Copper zinc superoxide dismutase (Cu/Zn SOD) activity was not reduced except with CS+HPP. During CS, we observed an increase in GPx, Cu/Zn SOD and Cat activity, a decrease in Mn SOD activity and no histological alterations in the kidney. CS induces a slight oxidative stress which is not important enough to induce major tissue damage. HPP with UWCSS induces a stronger stress, which overpowers the antioxidant defences, inducing tissue damage. The reperfusion of HPP with UWCSS emphasises the stress initiated by CS. In addition an increase in damage occurred in the CS + HPP group.

Adenosine↗
PubMed2002

Risk factors of fibrosis in alcohol-induced liver disease.

In patients with nonalcoholic steatohepatitis (NASH), age, obesity, and diabetes mellitus are independent predictors of the degree of fibrosis. The relative risk for fibrosis adjusted for sex was also associated with increasing grade of Perls stain. The aim of this study was to determine whether the risk factors for fibrosis described in NASH are also risk factors in alcohol-induced liver disease. A total of 268 alcoholic patients with negative hepatitis B virus and hepatitis C virus serology underwent liver biopsy. Fibrosis was assessed semiquantitatively by a score fluctuating between 0 to 8. Liver iron overload was assessed by Perls staining and graded in 4 classes. We have used multivariate regression with partial correlation analysis to assess the variability of fibrosis score according to the value of 7 variables: sex, age, body mass index (BMI) in the past year before the hospitalization when the patient was asymptomatic, daily alcohol intake over the past 5 years, total duration of alcohol abuse, Perls grade, and blood glucose level. In the multivariate regression, fibrosis score was positively correlated with age (P =.001), BMI (P =.002), female sex (P <.05), Perls grade (P <.05), and blood glucose level (P <.05). Twenty percent of the variability of fibrosis score was explained by the 7 variables. In conclusion, after adjustment for daily alcohol intake and total duration of alcohol abuse, BMI, Perls grade, and blood glucose are also independent risk factors for fibrosis in alcohol-induced liver disease, raising therapeutic implications for the management of these patients.

Age Factors↗
PubMed2002

Effects and regulation of connective tissue growth factor on hepatic stellate cells.

Connective tissue growth factor (CTGF) is a 38-kd protein involved in several human fibrotic disorders including atherosclerosis and skin and renal fibrosis. Although it has been shown that human and experimental liver fibrosis is associated with CTGF expression through up-regulation of CTGF mRNA by hepatic stellate cells (HSC), the role of CTGF in the liver has not yet been determined. The aim of the present study was to assess the effects of CTGF on rat primary HSC and its regulation in a well-established model of in vitro liver fibrogenesis. Incubation of primary HSC with recombinant CTGF induced a significant migratory (2.3-fold, 50 ng/ml CTGF) and proliferative effect (1.8-fold, 100 ng/ml CTGF). Type I collagen mRNA expression, as assessed by a real-time RT-PCR procedure, was also increased when cells were incubated in the presence of CTGF (2-fold, 50 ng/ml). Transforming growth factor-beta1 (TGF-beta1) strongly stimulated CTGF mRNA expression, a direct mechanism observed in the absence of any intermediate protein synthesis. Furthermore, spontaneous activation of HSC plated on plastic and stimulation by vascular endothelial growth factor, lipid peroxidation products (HNE, MDA), acetaldehyde, and platelet-derived growth factor (PDGF)-BB significantly up-regulated CTGF mRNA expression in HSC. PDGF-induced CTGF stimulation might be related in part to TGF-beta1 secretion because CTGF mRNA up-regulation observed after PDGF-BB stimulation was abrogated in the presence of neutralizing TGF-beta1 antibody. In conclusion, this study extends the role of CTGF in HSC activation and suggests that CTGF up-regulation might be a central pathway during HSC activation.

Animals↗
PubMed2002

Dystroglycan expression in hepatic stellate cells: role in liver fibrosis.

Dystroglycan is a membrane component of the dystrophin-glycoprotein transmembrane complex. Its expression is required for the spatial organization of laminin on the cell surface and for basement membrane assembly. In view of the constitution of a perisinusoidal basement membrane during liver fibrosis, we studied dystroglycan expression in liver fibrosis. Dystroglycan mRNA and protein expression were investigated by immunofluorescence, Western blot, and quantitative RT-PCR (TaqMan) in normal human and rat liver and in isolated rat hepatic stellate cells. On Western blot, a 43-kd band corresponding to beta-dystroglycan was observed in protein extracted from normal and fibrotic human and rat livers. The specific 43-kd protein was also detected in lysates from rat hepatic stellate cells but not from hepatocytes. By immunofluorescence, patchy deposits of beta-dystroglycan were detected on membrane of hepatic stellate cells in culture. On Western blot and quantitative RT-PCR, an up-regulation of beta-dystroglycan was shown during spontaneous activation of hepatic stellate cells in culture. Direct evidence for the role of dystroglycan in laminin-hepatic stellate cell interaction was shown because specific antibody directed against alpha-dystroglycan inhibited partially hepatic stellate cell adhesion on laminin-coated plates. This mechanism was calcium dependent because EDTA inhibited cell/laminin adhesion, an effect reversed by addition of Ca(2+). This study shows that dystroglycan is expressed on the membrane of hepatic stellate cells and is up-regulated during liver fibrosis. Dystroglycan interaction with laminin should be implicated in the concentration of pericellular laminin and in the constitution of a perisinusoidal basement membrane during liver fibrosis.

Animals↗
PubMed2002

[Standards, Options and Recommendations for the management of patient with carcinoma of unknown primary site].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Cancer Centers, and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for carcinoma of unknown primary site (CUPS) patients according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 81 independent reviewers. RESULTS: The main recommendations for the management of patients CUPS are presented below: 1) An adapted immunochemistry test using a specific antibody battery should be performed for the anatomopathologic diagnosis. 2) The aim of the diagnosis is to identify specific anatomoclinical forms that can be treated by a specific treatment (standard, level of evidence B2). Except these forms, searching for the primary tumor site have no prognosis or therapeutic interest that can justify a systematic diagnosis assessment (standard, level of evidence B2). 3) The management of poorly differentiated neuroendocrine carcinoma consists of platin/etoposide based chemotherapy. There is no standard treatment for the differentiated forms. 4) Surgical node excision and adjuvant radiotherapy should be performed in case of epidermoid carcinoma with cervical node metastases. In the event of a non operable tumor, an irradiation should be performed. 5) The management of axillary node metastases in women with adenocarcinoma should be the same as the management of patients with lymph node metastases in breast cancer. If mammary MRI is negative, surgical treatment and mammary irradiation are not recommended and an axillary node excision should be performed. 6) The standard treatment for women with primary papillary serous carcinoma of the peritoneum is a surgical resection followed by chemotherapy, as recommended for ovarian cancer. 7) CUPS not belonging to any specific anatomoclinical forms can be treated by chemotherapy, symptomatic treatment alone or treatment based on biphosphonates in presence bone metastases.

Axilla↗
PubMed2002

[Neoplastic intraepithelial lesions of pancreatic ducts: new entities].

Intraductal neoplastic lesions of the pancreas have been the focus of recent efforts aiming to better characterize several entities. Beside reactive papillary hyperplastic lesion of pancreatic ducts whose limits and significance are unclear, two different entities, intraductal papillary mucinous neoplasm (IPMN) with its variant intraductal oncocytic papillary neoplasm, and pancreatic intraepithelial neoplasia (PanIN), the precursors of pancreatic adenocarcinoma have been recognized. Each has been carefully described at the microscopic level with classification into several grades of dysplasia. IPMNs are intraductal, papillary, often diffuse and mucus hypersecreting neoplastic lesions. Mucin accumulation gives to the lesion a cystic pattern. Treatment is surgical resection of the whole lesion. Intraductal oncocytic papillary neoplasm is a rare variant of IPMN. The prognosis of IPMN is globally favorable, but these tumors display the risk of malignant transformation into a mucinous or a tubular pancreatic adenocarcinoma. Although IPMN can induce symptoms, PanIN are silent and always discovered at the vicinity of an invasive adenocarcinoma. The usefulness and the reproducibility of the classification of PanIN remain to be determined. PanIN classification might resume the different successive steps of molecular genetic or epigenetic events associated with the development of a pancreatic carcinoma.

Adenocarcinoma, Mucinous↗