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Frédérique Capron

Publications and source records attributed to Frédérique Capron.

At least 19 recordsLinked to original sources
PubMed2007

Late recurrence of a prostatic adenocarcinoma as a solitary splenic metastasis.

Splenic metastases of solid tumors are exceptional. We report the first case of an isolated splenic metastasis from prostate carcinoma, 5 years after radical prostatectomy. The splenic tumor was revealed by a pain and progressive increase in the serum prostate-specific antigen (PSA) level. Histology of the spleen showed an adenocarcinoma immunostained with cytokeratin and PSA markers. The patient remained asymptomatic and his serum PSA level was within normal limits 17 months after the splenectomy. This case suggests that splenic metastasis might be the result of the growth of an early blood-borne micrometastasis within the spleen after a period of clinical latency.

Adenocarcinoma↗
PubMed2006

Pulmonary vascular lesions in end-stage idiopathic pulmonary fibrosis: Histopathologic study on lung explant specimens and correlations with pulmonary hemodynamics.

In patients presenting with idiopathic pulmonary fibrosis (IPF), modifications of pulmonary vessels are well defined in fibrotic areas but have not been accurately assessed in the intervening patches of preserved lung. Moreover, the relation between pulmonary vessel lesions and pulmonary hemodynamics is not well known. We therefore designed a retrospective study on lung explant specimens from 26 patients with a firm diagnosis of IPF who had undergone lung transplantation. Our aim was to (1) describe the vascular lesions, especially in preserved lung areas, and (2) correlate them with pulmonary hemodynamics. In dense fibrotic zones, thickening of the arterial and venous wall with severe luminal narrowing was present in each patient. In architecturally preserved lung zones, occlusion of venules and small pulmonary veins was observed in 65% of the patients, although there were only mild changes of muscular pulmonary arteries. We found a significant positive correlation between the macroscopic extent of lung fibrosis and mean pulmonary artery pressure, but we failed to find a relation between mean pulmonary artery pressure and venous/venular lesions in nonfibrotic areas. Our study points out that in many patients with IPF, nonfibrotic lung areas demonstrate an occlusive venopathy, the signification of which remains undetermined.

Adult↗
PubMed2006

Bronchoalveolar lavage cytological alveolar damage in patients with severe pneumonia.

INTRODUCTION: Histological examination of lung specimens from patients with pneumonia shows the presence of desquamated pneumocytes and erythrophages. We hypothesized that these modifications should also be present in bronchoalveolar lavage fluid (BAL) from patients with hospital-acquired pneumonia. METHODS: We conducted a prospective study in mechanically ventilated patients with clinical suspicion of pneumonia. Patients were classified as having hospital-acquired pneumonia or not, in accordance with the quantitative microbiological cultures of respiratory tract specimens. A group of severe community-acquired pneumonias requiring mechanical ventilation during the same period was used for comparison. A specimen of BAL (20 ml) was taken for cytological analysis. A semiquantitative analysis of the dominant leukocyte population, the presence of erythrophages/siderophages and desquamated type II pneumocytes was performed. RESULTS: In patients with confirmed hospital-acquired pneumonia, we found that 13 out of 39 patients (33.3%) had erythrophages/siderophages in BAL, 18 (46.2%) had desquamated pneumocytes and 8 (20.5%) fulfilled both criteria. Among the patients with community-acquired pneumonia, 7 out of 15 (46.7%) had erythrophages/siderophages and 6 (40%) had desquamated pneumocytes on BAL cytology. Only four (26.7%) fulfilled both criteria. No patient without hospital-acquired pneumonia had erythrophages/siderophages and only 3 out of 18 (16.7%) had desquamated pneumocytes on BAL cytology. CONCLUSION: Cytological analysis of BAL from patients with pneumonia (either community-acquired or hospital-acquired) shows elements of cytological alveolar damage as hemorrhage and desquamated type II pneumocytes much more frequently than in BAL from patients without pneumonia. These elements had a high specificity for an infectious cause of pulmonary infiltrates but low specificity. These lesions could serve as an adjunct to diagnosis in patients suspected of having ventilator-associated pneumonia.

Bronchoalveolar Lavage Fluid↗
PubMed2005

Ocular adnexal marginal zone B cell lymphoma: a clinical and pathologic study of 23 cases.

To better characterize ocular adnexal marginal zone lymphoma of mucosa-associated lymphoid tissue (MZL-MALT), we analyzed the clinical and pathologic features of 23 patients (11 men, 12 women, median age 66 years). The tumor was confined to one ocular structure in 18 cases (conjunctiva, n=8; orbit, n=8; or lacrimal gland, n=2). Concurrent extraorbital disease was detected by the staging procedure in five patients, and preferentially involved other MALT sites. Histogenetic B cell marker studies, available in 13 cases, showed an early post-germinal center (GC) phenotype (BCL-6(-)/IRF4(+)/CD138(-)) (n=5) or a late post-GC phenotype (BCL-6(-)/IRF4(+)/CD138(+)) (n=8), which could be helpful for discrimination from other types of small-B cell lymphoma. BCL10 was positive in 12 of 13 patients tested, with nuclear (n=4) or cytoplasmic (n=8) immunoreactivity. These staining patterns ruled out t(1;14)(p22;q32) translocation. T(11;18)(q21;q21), another MZL-MALT-specific translocation, was detected by reverse transcriptase polymerase chain reaction in four of 15 patients tested. Clinical outcome was excellent but the overall relapse rate was 26.1% with a median follow-up of 39 months (range 6-132 months). Regardless of the disease stage at diagnosis, combined chemotherapy and radiotherapy seemed to be more effective than chemotherapy alone in ocular adnexal MZL-MALT, as persistent complete remission was achieved in nine patients receiving combination therapy, while six of 14 patients treated with chemotherapy alone relapsed.

Adult↗
PubMed2005

High-dose acetylcysteine in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS: We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) added to standard therapy with prednisone plus azathioprine. The primary end points were changes between baseline and month 12 in vital capacity and in single-breath carbon monoxide diffusing capacity (DL(CO)). RESULTS: A total of 182 patients were randomly assigned to treatment (92 to acetylcysteine and 90 to placebo). Of these patients, 155 (80 assigned to acetylcysteine and 75 to placebo) had usual interstitial pneumonia, as confirmed by high-resolution computed tomography and histologic findings reviewed by expert committees, and did not withdraw consent before the start of treatment. Fifty-seven of the 80 patients taking acetylcysteine (71 percent) and 51 of the 75 patients taking placebo (68 percent) completed one year of treatment. Acetylcysteine slowed the deterioration of vital capacity and DL(CO): at 12 months, the absolute differences in the change from baseline between patients taking acetylcysteine and those taking placebo were 0.18 liter (95 percent confidence interval, 0.03 to 0.32), or a relative difference of 9 percent, for vital capacity (P=0.02), and 0.75 mmol per minute per kilopascal (95 percent confidence interval, 0.27 to 1.23), or 24 percent, for DL(CO) (P=0.003). Mortality during the study was 9 percent among patients taking acetylcysteine and 11 percent among those taking placebo (P=0.69). There were no significant differences in the type or severity of adverse events between patients taking acetylcysteine and those taking placebo, except for a significantly lower rate of myelotoxic effects in the group taking acetylcysteine (P=0.03). CONCLUSIONS: Therapy with acetylcysteine at a dose of 600 mg three times daily, added to prednisone and azathioprine, preserves vital capacity and DL(CO) in patients with idiopathic pulmonary fibrosis better than does standard therapy alone.

Acetylcysteine↗
PubMed2005

Follistatin allows efficient retroviral-mediated gene transfer into rat liver.

Retroviral vectors are widely used tools for gene therapy. However, in vivo gene transfer is only effective in dividing cells, which, in liver, requires a regenerative stimulus. Follistatin is effective in promoting liver regeneration after 90% and 70% hepatectomy in rats. We studied its efficacy on liver regeneration and retroviral-mediated gene delivery in 50% hepatectomized rats. When human recombinant follistatin was infused into the portal vein immediately after 50% hepatectomy, hepatocyte proliferation was significantly higher than in control 50% hepatectomized rats. A single injection of virus particles administered 23 h after follistatin infusion resulted in more than 20% gene transduction efficiency in hepatocytes compared to 3% in control rats. It is concluded that a single injection of follistatin induces onset of proliferation in 50% hepatectomized rats and allows efficient retroviral-mediated gene transfer to the liver.

Animals↗
PubMed2005

Long-term controlled immortalization of a primate hepatic progenitor cell line after Simian virus 40 T-Antigen gene transfer.

Hepatoblasts are bipotent progenitors of both hepatocytes and cholangiocytes. The lack of stable in vitro culture systems for such cells makes it necessary to generate liver progenitor cell lines by means of immortalization. In this study, we describe the long-term behaviour of a clone of simian foetal hepatic progenitor cells immortalized by Simian virus 40 (SV40) large T-antigen (T-Ag) flanked by loxP sites. Immortalization was associated with the re-expression of telomerase activity, which decreased at late passages (population doubling 120) after more than a year in culture. This decrease was concomitant to telomere shortening and karyotypic instability. However, the chromosomes carrying the p53 gene remained intact and long-term immortalized progenitor cells maintained contact inhibition and proliferative properties. They also displayed the features of a normal bipotent phenotype. We constructed a retroviral vector expressing an inducible Cre recombinase and transferred it into the immortalized progenitors. Activation of the Cre recombinase by 4-hydroxy-tamoxifen induced SV40 T-Ag excision, leading to the death of cells expressing Cre recombinase. Immortalized progenitors at late passages stopped growing and eventually disappeared after transplantation into the livers of immunocompromised mice. These cells provide a novel model to study hepatic differentiation and carcinogenesis.

Animals↗
PubMed2005

Balance between pro and anti-inflammatory cytokines in patients with acute alcoholic hepatitis.

UNLABELLED: The ability of endogenous IL-10 to modulate inflammatory response and to limit hepatotoxicity has been shown in several models of liver injury. AIMS: The objectives of this study were to evaluate the relationship between liver disease and the balance between pro and anti-inflammatory cytokines in acute alcoholic hepatitis. METHODS: Twenty-five patients with pure steatosis, 17 with cirrhosis and mild acute alcoholic hepatitis (discriminant function value<32) and 41 patients with cirrhosis and severe acute alcoholic hepatitis (discriminant function value >=32) were studied. Plasma levels of interleukin 10 (IL-10) and soluble TNF receptors (TNFsRp75 and 55) were analyzed using ELISA assays. Hepatocyte proliferative activity was assessed with proliferating cell nuclear antigen labeling index (PCNA-LI) on formalin-fixed paraffin embedded liver biopsy specimens. RESULTS: In patients with steatosis, cirrhosis with mild and severe acute alcoholic hepatitis, the plasma levels of IL-10 were higher (P<0.05) than in healthy controls. Between day 1 and day 8, the TNFsRp55/IL-10 ratio increased by 137 +/- 47 in the 10 patients with severe acute alcoholic hepatitis treated with prednisolone who died within 2 months and by 9.3 +/- 14 in the 19 patients still alive at 2 months (P=0.031). In patients with severe acute alcoholic hepatitis, PCNA-LI on liver biopsy was negatively correlated with the TNFsRp55/IL-10 ratio increase from day 1 to day 8 (r=- 0.42, P=0.11). PCNA-LI was positively correlated with TNFsRp75/TNFsRp 55 ratio increase from day 1 to day 15 (r=0.52; p<0.05). CONCLUSION: Our data suggest the anti-inflammatory system is up-regulated in patients with alcoholic liver disease. Nevertheless, in patients with severe acute alcoholic hepatitis, IL-10 production seems insufficient to modulate TNF-alpha cytotoxicity mediated by TNFRp55.

Acute Disease↗
PubMed2005

[An unusual cause of jejunal intussusception: heterotopic and hyperplastic Brunner's gland pseudo-tumor].

We report the first case of small-bowel intussusception caused by a tumour-like Brunner's gland hyperplasia in a 26 year old woman. The patient presented with intense abdominal pain. Abdominal and pelvic contrast enhanced CT-scan suggested small bowel intussusception involving the first jejunal loop. A 15 cm long polypoid mass was found in the jejunumectomy specimen (2nd and 3rd loops). Histological examination revealed Brunner's gland hyperplasia in the jejunal mucosa and submucosa. Considering the jejunal location of the lesion, it must be considered malformative and heterotopic Brunner's gland hyperplasia.

Abdominal Pain↗
PubMed2005

[New classification of interstitial lung disease].

The pathological classification of interstitial lung disease (ILD) includes two general groups, diffuse infiltrative pneumonia with a specific histological presentation due to primary disease of unknown or unrecognized cause and idiopathic ILD. Diagnosis is established on the basis of clinical, radiological and pathological findings. In the first group of diffuse infiltrative pneumonia, the diagnosis is usually straightforward, established on endoscopic biopsy, alveolar lavage or surgical material depending on the case. The pathological classification of idiopathic ILD requires a surgical specimen. The entities redefined by the American Thoracic Society and the European Respiratory Society (ATS/ERS) are: usual interstitial pneumonia, non specific interstitial pneumonia, chronic organized pneumonia, diffuse alveolar damage, desquamative interstitial pneumonia, desquamative interstitial pneumonia with respiratory bronchiolitis and lymphocytic interstitial pneumonia. The diagnosis of idiopathic pulmonary fibrosis is established in a precise clinical and radiological context with an aspect of common interstitial pneumonia of the biopsy material. It is important to recognized common interstitial pneumonia because of the severe prognosis and to distinguish it from non-specific ILD.

Biopsy↗
PubMed2005

Biomarkers for the prediction of liver fibrosis in patients with chronic alcoholic liver disease.

BACKGROUND & AIMS: The aim of this study was to determine the diagnostic use of noninvasive markers of fibrosis in patients with chronic alcoholic liver disease. METHODS: A total of 221 consecutive patients with an alcohol intake of >50 g/day (median, 100 g/day) and available liver biopsy examination and FibroTest FibroSure (FT) results were included prospectively. Fibrosis was assessed blindly on a 5-stage histologic scale similar to that of the METAVIR scoring system. Hyaluronic acid was measured and used as a standard serum marker of fibrosis. RESULTS: Advanced fibrosis (F2-F4) was present at biopsy examination in 63% of patients. The mean FT value (SE) was F0 = .29 (.05); F1 = .29 (.03), F2 = .40 (.03), F3 = .53 (.04); and F4 = .88 (.02) (P < .05 between all groups, except between F0 and F1). As opposed to FT, there was no significant difference for hyaluronic acid between F2 and F1 and between F2 and F0. For F2-F4 vs. F0-F1, the FT area under the ROC curves (AUROC) = .84 (.03) and .79 (.03) for hyaluronic acid. For the diagnosis of F4, the AUROC was very high, .95 for FT and .93 for hyaluronic acid. The discordances of the 2 stages were attributed to biopsy failures in 26 cases and to FT failures in 13 cases. CONCLUSIONS: In heavy drinkers, FT is a simple and noninvasive quantitative estimate of liver fibrosis. The use of FT may decrease the need for liver biopsy examination.

Biomarkers↗
PubMed2005

Sampling variability of liver biopsy in nonalcoholic fatty liver disease.

BACKGROUND & AIMS: In nonalcoholic fatty liver disease (NAFLD), the distinction between steatosis and steatohepatitis (NASH) and the assessment of the severity of the disease rely on liver histology alone. The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH. METHODS: Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 samples collected. The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the kappa reliability test. RESULTS: No features displayed high agreement; substantial agreement was only seen for steatosis grade; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis; fair agreement for Mallory bodies; acidophilic bodies and lobular inflammation displayed only slight agreement. Overall, the discordance rate for the presence of hepatocyte ballooning was 18%, and ballooning would have been missed in 24% of patients had only 1 biopsy been performed. The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74. Discordance of 1 stage or more was 41%. Six of 17 patients with bridging fibrosis (35%) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy. Intraobserver variability was systematically lower than sampling variability and therefore could not account for most of the sampling error. CONCLUSIONS: Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma; therefore, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies.

Adult↗
PubMed2005

Skin metastases from unknown origin: role of immunohistochemistry in the evaluation of cutaneous metastases of carcinoma of unknown origin.

Determining the primary origin of skin metastases might be a challenging issue for pathologists, especially when there is no primary history or when this history is unavailable. The poor specificity of morphological appreciation is challenging, emphasizing the need for ancillary studies. We have retrieved 44 cases of skin metastases from our pathology files. Paraffin blocks were collected and homemade tissue arrays were made. We have tried to assess the primary origin based on morphological data alone, and then using 13 antibodies (cytokeratins (CK) 5/6, 7, 19, 20, thyroid transcription factor-1, carcinoembryonic antigen, PS100, tumor-associated glycoprotein 72, BerEP4, estrogen receptor (ER), progesterone receptor (PR), CD10, and E-cadherin). Most metastases in our series were from breast (13) and colorectal cancers (six) as they are the main clinical activity in our hospital. Only 44% of cases were correctly assessed based on the sole morphology, emphasizing the need for ancillary studies. CK 20, ER, and PR were the most helpful markers to determine the primary origin of skin metastases by highlighting colorectal origin and mammary origin, respectively. By far, clinical information and morphological evaluation are more reliable than the use of ancillary techniques, which have to be used in the absence of the former one and the poor differentiation of the latter ones. Azoulay S, Adem C, Le Pelletier F, Barete S, Francès C, Capron F. Skin metastases from unknown origin: role of immunohistochemistry in the evaluation of cutaneous metastases of carcinoma of unknown origin.

Adenocarcinoma↗
PubMed2004

Pericardial ectopic thymoma.

Primary intrapericardial thymoma is an unusual localization. We report a case of a patient with an isolated and primary pericardial thymoma. This 72-year-old woman presented with dyspnea, dysphony and myalgia. The radiological evaluation revealed an intrapericardial mass. Surgical exploration showed a hemorrhagic and infiltrative tumor in the pericardial sac, while the mediastinum was free of tumor. Surgical biopsies and, later, an ablation of pericardial mass were done. The tumor was a thymoma, composed of large epithelial cells and immature T lymphocytes and was classified B2 according to the World Health Organization classification (1999). Clinically, a myasthenia gravis was revealed. We discuss the few cases reported in the literature.

Aged↗
PubMed2004

Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer.

The clinical impact of circulating tumor cell (CTC) detection is controversial, mainly due to drawbacks of molecular approaches applied to this field. We sought to determine if the specific identification and counting of circulating tumor cells by cytomorphologic analysis has clinical usefulness. Peripheral blood (6 mL), treated using isolation by size of epithelial tumor cells, was obtained from 44 patients with primary liver cancer (PLC) and without metastases, 30 patients with chronic active hepatitis, 39 with liver cirrhosis, and 38 healthy individuals, and followed up for a mean period of 1 year. We searched for beta-catenin mutations in 60 single microdissected CTCs. One patient with liver cancer developed extrahepatic metastases during follow-up. CTCs and microemboli were found in 23 of the 44 patients with liver cancer and in none of the patients with chronic active hepatitis, patients with cirrhosis, or healthy subjects. Their presence was significantly associated with tumor diffusion (P =.0001) and portal tumor thrombosis (P =.006). Both the presence (P =.01) and number (P =.02) of CTCs and microemboli were significantly associated with a shorter survival. Beta-catenin mutations were found in 3 of 60 CTCs, arguing against their impact on the initial step of tumor cell invasion. In conclusion, the highly sensitive and specific detection of CTCs and microemboli may have clinical implications for cancer staging and outcome prediction. We also show the feasibility of molecular studies of individual circulating tumor cells, aimed at identifying gene mutations involved in tumor invasion.

Aged↗
PubMed2004

Portal branch ligation induces efficient retrovirus-mediated gene delivery in rat liver.

BACKGROUND: The in vivo transduction of hepatocytes with conventional retrovirus vectors requires the induction of cell division and this can currently only be achieved by invasive surgery or by inducing severe liver damage. We hypothesised that partial portal branch ligation (PBL) could induce hepatocyte proliferation and efficient gene transfer in the rat. METHODS: We ligated the portal branch serving 70% of the liver and measured the kinetics of liver mass restoration and cell proliferation and the distribution of dividing hepatocytes after administration of 5-bromo-2'-deoxyuridine. The efficiency of retrovirus-mediated gene transfer after PBL was tested by use of beta-galactosidase-expressing recombinant retroviruses. The viruses were administered in a single injection via the portal vein at different times after PBL and the livers of transduced animals were analysed 4 days later. RESULTS: We found that the number of cycling hepatocytes remained stable between 24 and 44 h after PBL (approximately 12.5%). Although there was a high level of inter-animal variability, hepatocyte proliferation was always initiated in the same lobe of the liver. In animals that had undergone PBL, 19% of hepatocytes were transduced 28 h after the administration of a single high-titre injection of retroviruses, mainly around the portal spaces. CONCLUSIONS: PBL can mediate the efficient transduction of hepatocytes in vivo after a single intravenous injection of recombinant retroviruses. This approach is feasible in humans.

Animals↗
PubMed2004

Repopulation of athymic mouse liver by cryopreserved early human fetal hepatoblasts.

Transplantation of hepatocytes is a promising alternative to liver transplantation for the treatment of severe liver diseases. However, this approach is hampered by the shortage of donor organs and intrinsic limitations of adult hepatocytes. To investigate whether most of the hurdles faced with adult hepatocytes could be surmounted by the use of human fetal hepatoblasts, we have developed a method to isolate, transduce, and cryopreserve hepatoblasts from human livers at an early stage of development (11-13 weeks of gestation). Cells were characterized in vitro for expression of specific markers, and in vivo for their proliferation and differentiation potential after transplantation into athymic mice. Most of the cells (80-90%) harbored a bipotent phenotype, expressing cytokeratins 8/18, albumin, and CK19. They proliferated spontaneously in culture and were efficiently transduced by a beta-galactosidase-expressing retrovirus (90%). After transplantation, cryopreserved cells engrafted into the liver of athymic mice and proliferated, resulting in up to 10% repopulation. Engrafted cells expressed markers of differentiated adult hepatocytes including albumin, alpha1-antitrypsin, cytochrome P450 3A4, and alpha-glutathione-S-transferase. When retrovirally transduced before transplantation they expressed the transgene in vivo. In summary, early human fetal hepatoblasts engraft, proliferate, and mature in athymic mouse liver, without conditioning the donor.

Albumins↗