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P Bedossa

Publications and source records attributed to P Bedossa.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Gastric epithelioid angiosarcoma, a biopsy diagnostic pitfall].

We report the case of a 70-year-old man who presented a bulky gastric mass. The diagnosis of poorly differenciated adenocarcinoma was made on the biopsy. On surgical specimen, the final diagnosis of gastric angiosarcoma with secondary intestinal involvement was established. The patient did not respond to chemotherapy and died 8 months later. The diagnosis was difficult because of epithelioid areas which expressed both cytokeratin and vascular antigens. Human herpesvirus 8 previously detected in some soft tissue angiosarcoma was not found by polymerase chain reaction.

Aged↗
PubMed2000

Expression of vascular endothelial growth factor in renal cell carcinomas.

Vascular endothelial growth factor (VEGF) is an angiogenic factor that may be involved in tumor growth and metastasis. Only a few data concerning the role of VEGF in renal cell carcinomas (RCCs) are available, and no studies have yet evaluated its prognostic value. The aim of the present study was to assess VEGF expression in a large series of renal tumors with a long follow-up, correlated with the usual histoprognostic factors and survival. VEGF immunostaining was performed on formalin-fixed, paraffin-embedded archival tissue from 74 renal carcinomas (62 conventional renal cell and 12 papillary carcinomas). Positivity of immunostaining was semi-quantitatively scored by two pathologists. Angiogenesis was evaluated by immunostaining with anti-CD34 antibodies on serial sections. Cytoplasmic VEGF expression was detected in tumor cells in 35% (26/74) of RCCs, including 18 out of the 62 (29%) conventional RCCs and 8 out of the 12 (67%) papillary carcinomas (P=0.02). In the group of conventional RCCs, VEGF expression was positively correlated with both nuclear grade (P=0.05) and size of the tumor (P=0.05). Furthermore, a significant correlation was observed between VEGF expression and microvascular count (P=0.04). Finally, cumulative survival rate was significantly lower in the group of patients with conventional RCCs expressing VEGF (log rank test, P=0.01). In the Cox model, VEGF expression was a significant independent predictor of outcome, as well as stage and nuclear grade. This study suggests that VEGF is involved in angiogenesis in conventional RCCs and appears to be a potential prognostic factor in these tumors.

Blood Vessels↗
PubMed2000

Clonal analysis of micronodules in virus C-induced liver cirrhosis using laser capture microdissection (LCM) and HUMARA assay.

Most hepatocellular carcinomas (HCC) arise from malignant transformation of regenerative cirrhotic nodules. Because HCC has a very poor prognosis, detection of these premalignant lesions may improve the management of patients with cirrhosis. In this regard, clonal analysis of liver micronodules should be of particular interest in order to differentiate polyclonal regenerative micronodules from monoclonal neoplastic potentially malignant micronodules. To address this issue, 112 micronodules from 15 cases of explanted liver cirrhosis were carefully microdissected from paraffin-embedded tissue using a laser capture microscopy system. Clonal analysis was performed by analyzing X-chromosome inactivation, as indicated by the methylation status of the human androgen receptor gene (HUMARA). For each microdissected micronodule, a large set of pathological features was evaluated and correlated with their clonal status. Clonal analysis showed that 57 micronodules (51%) were monoclonal and 55 (49%) were polyclonal. Prevalence of monoclonal nodules ranged from 25% to 71% according to cases. In all cases, mono- and polyclonal nodules were randomly distributed in the cirrhotic liver. Although the clonal status was not significantly affected by the presence or absence of macronodules in the adjacent liver, size of monoclonal micronodules was significantly larger than size of polyclonal micronodules (mean size of the monoclonal nodules: 3 + 0.1 mm vs mean size of the polyclonal nodules: 2.5 +/- 0.1 mm, p = 0.007). Among the elementary pathological features evaluated, only the presence of iron overload was correlated with a monoclonal status (p = 0.04). In conclusion, clonal analysis of liver cirrhosis shows that 51% of micronodules are monoclonal lesions, supporting the notion that liver cirrhosis is a multineoplastic lesion. Because monoclonality is a marker of neoplasia, cirrhosis with accumulation of monoclonal nodules may be carefully followed, and monoclonal nodules should be screened for additional markers to assess their biological behavior.

Adult↗
PubMed2000

Natural history of HCV infection.

Chronic hepatitis C virus (HCV) infection affects 170 million individuals worldwide. These individuals are at risk of developing both hepatological and non-hepatological manifestations. HCV is usually only fatal when it leads to cirrhosis, the final stage of liver fibrosis. Therefore, an estimate of fibrosis progression represents an important surrogate end-point for the evaluation of the vulnerability of an individual patient. In untreated patients, the median expected time to cirrhosis is 30 years; 33% of patients have an expected median time to cirrhosis of less than 20 years and 31% will only progress to cirrhosis after more than 50 years, if ever. Several factors are associated with fibrosis progression rate: duration of infection, age, male gender, consumption of alcohol, HIV co-infection and low CD4 count. Non-hepatological manifestations are frequent with more than 70% of HCV patients experiencing fatigue or at least one extrahepatic clinical manifestation involving primarily the joints, skin and muscles. Several immunological abnormalities are frequently observed, including cryoglobulins (40%),anti-nuclear antibodies (10%) and anti-smooth muscle antibodies (7%). In contrast severe extrahepatic manifestations are rare, with 1% for systemic vasculitis.

Antibodies, Antinuclear↗
PubMed2000

Impact of interferon alfa-2b and ribavirin on progression of liver fibrosis in patients with chronic hepatitis C.

The extent of liver fibrosis is an important prognostic factor in patients infected with hepatitis C virus. Administration of a combination of interferon and ribavirin produces a superior viral clearance response rate than interferon alone. The effect of this combination regimen on hepatic fibrosis has not been established. To determine the impact of combination regimen or interferon alone on the progression of liver fibrosis we pooled individual data of 1,509 patients with pretreatment and post-treatment biopsies from 3 randomized trials. Fibrosis progression and regression rates between biopsies were calculated by the Kaplan-Meier method and by the fibrosis progression rate per year. The percentage of patients without significant fibrosis (stage 0 or 1) at 96 weeks was 68 +/- 4% (mean +/- SE) when treated by combination regimen for 48 weeks, 64 +/- 4% by interferon alone for 48 weeks, 42 +/- 7% by combination regimen for 24 weeks (lower than both 48-week regimens P <.001), and 24 +/- 9% interferon alone for 24 weeks (lower than the combination regimen for 24 weeks; P =.02). Three factors were independently associated with fibrosis reduction: sustained viral response, duration of treatment, and baseline fibrosis stage (all P <.001 in proportional hazards regression model). These results show that interferon and ribavirin combination therapy significantly reduces the rate of fibrosis progression in patients with hepatitis C. This effect was most prominent in patients who achieved a virologic response, those receiving 48 weeks of therapy, and in patients with significant fibrosis at baseline.

Adult↗
PubMed2000

Fibrosis in patients with chronic hepatitis C: detection and significance.

Estimates of the extent of hepatic fibrosis and the rate of fibrosis progression represent important surrogate end points for evaluation of the vulnerability of an individual patient and for assessment of the impact of treatment on natural history in chronic hepatitis C. Using the median fibrosis progression rate, the median expected time to cirrhosis in untreated patients is around 30 years. However, one third of patients have an expected median time to cirrhosis of less than 20 years and one third will only progress to cirrhosis in more than 50 years, if ever. Factors independently associated with fibrosis progression are duration of infection, age, male gender, consumption of alcohol, human immunodeficiency virus co-infection, and low CD4 count. Evaluation of fibrosis progression is useful to decide treatment. Among patients with sustained viral response, fibrosis regresses. Evaluation of fibrosis progression has permitted validation of the concept of suppressive therapy. Among patients without viral clearance, interferon alone or in combination with ribavirin significantly reduces fibrosis progression rate in comparison with progression before treatment and to control groups. There is a major need for noninvasive markers of liver fibrosis. None are clearly useful today for the diagnosis of early stages of fibrosis.

Antiviral Agents↗
PubMed2000

Appropriateness of liver biopsy.

This review aims to discuss the appropriateness of liver biopsy in two frequent liver diseases, hepatitis C and alcoholic liver disease. The medical literature, published between 1965 and 1999, was reviewed by using MEDLINE. Only 0.1% of the publications were devoted specifically to the appropriateness of liver biopsy. Not all studies observed a significant agreement among doctors on the decision to use liver biopsy. Therefore, there is a possibility that hepatologists have significant, heterogeneous opinions concerning the appropriateness of liver biopsy. Appropriateness should be evaluated for different techniques such as percutaneous liver biopsy, guided or not by ultrasonography, and the types of needles, automatic or not. The present paper reviews the evaluation of liver biopsy appropriateness in the real world, the adverse events and mortality of liver biopsy, and the appropriateness of liver biopsy in alcoholic liver disease and chronic hepatitis C. The authors conclude that liver biopsy is used extensively, but its appropriateness has not been evaluated perfectly. Therefore, further evaluation of the appropriateness of liver biopsy in the practical algorithm of such diseases is needed.

Biopsy↗
PubMed2000

Quantitation of hTERT gene expression in sporadic breast tumors with a real-time reverse transcription-polymerase chain reaction assay.

Recent observations support the notion that telomerase expression is essential for the formation of human tumor cells [W-C. Hahn et al., Nature (Lond.), 400: 464-468, 1999]. The expression pattern of hTERT, the human telomerase catalytic subunit gene, is a rate-limiting determinant of the enzymatic activity of human telomerase. We have developed a real-time quantitative RT-PCR assay based on Taq-Man fluorescence methodology to quantify the full range of hTERT mRNA copy numbers. We validated the method on a series of 134 unilateral invasive primary breast cancer patients with known long-term outcome. Three-quarters of the breast tumors (75.4%; 101 of 134) were hTERT positive, i.e., contained detectable and quantifiable hTERT mRNA. hTERT-positive patients had significantly shorter relapse-free survival (P = 0.017) after surgery compared with hTERT-negative patients. The prognostic significance of hTERT status persisted in Cox multivariate regression analysis. When we subdivided hTERT-positive patients (n = 101) into three equal groups (tumors showing small, intermediate, or high increase in hTERT mRNA content), we observed statistical (or a trend toward) links between high hTERT mRNA levels and Scarff-Bloom-Richardson histopathological grade III (P = 0.066), and negative estrogen (P = 0.002) and progesterone (P = 0.048) receptor status, and therefore with higher aggressiveness of breast tumors. High hTERT mRNA levels were also linked to MYC gene overexpression (P = 0.007). These findings show that the quantitative evaluation of hTERT mRNA can have important prognostic significance in human breast cancer. In addition, our simple, rapid, and semiautomated assay method is suitable for routine hTERT mRNA detection and quantification and will be a powerful tool in large, randomized, prospective, cooperative group trials and in the hTERT-based therapy project.

Adult↗
PubMed2000

[Solid and pseudopapillary tumor of the pancreas: immunohistochemical and ultrastructural study of 2 pediatric cases].

We report 2 cases of solid and pseudopapillary tumors of the pancreas occurring in female children. Lesions were made of uniform small cells arranged in solid areas associated with pseudopapillary and cystic patterns. Immunohistochemistry study was positive for neuron-specific enolase, alpha-1 anti-trypsin and vimentin. Ultrastructural study showed an abundant cytoplasm, rich in mitochondria, containing a lot of granules of variable sizes, often disintegrated, and some lipid droplets. The differential diagnosis of this lesion included endocrine tumor, pancreatoblastoma and acinar cell carcinoma. It is a rare tumor of the pancreas with a favorable prognosis after complete resection.

Adolescent↗
PubMed1999

Expression of the RNA component of human telomerase (hTR) in prostate cancer, prostatic intraepithelial neoplasia, and normal prostate tissue.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA on chromosomal ends. While telomerase is undetectable in most normal somatic tissues, telomerase activation has been detected by a polymerase chain reaction (PCR)-based assay (TRAP) in many immortal cell lines and various cancers, including prostate cancers. To investigate the role of telomerase in prostate cancer at the cellular level, the expression of one of the ribonucleoprotein complexes, the RNA component of human telomerase (hTR), was studied in normal, preneoplastic, and cancerous prostate tissues using a non-radioactive in situ hybridization procedure. Nine human prostates resected at the time of radical prostatectomy were studied. In each case, archival paraffin-embedded samples from normal tissue, prostatic intraepithelial neoplasia (PIN) lesions, the putative precancerous lesion, and prostate carcinomas were selected for in situ hybridization. hTR mRNA expression was detected in carcinomatous glands of seven out of the nine cancers (75 per cent). Furthermore, in seven out of the eight cases showing PIN lesions, the epithelial cells of PIN foci also expressed hTR mRNA. By contrast, in normal tissue, epithelial cells were negative, whereas hTR mRNA expression was detected in the basal cells. The detection of hTR mRNA in PIN lesions clearly strengthens the link between PIN and carcinomatous glands and suggests that telomerase expression occurs early in prostate carcinogenesis. Furthermore, this study confirms previous experimental data suggesting that the basal cell layer is the stem cell compartment in prostate.

Aged↗