Frédérique Capron

Hôpital La Pitié Salpêtrière – Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix", Paris, Ile-de-France, France

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Publications (27)121.13 Total impact

  • Article: [An unusual mutinodular goiter].
    Annales de Pathologie 12/2009; 29(6):528-30. · 0.25 Impact Factor
  • Article: [Fatal cardiac failure following antibiotic treatment].
    Annales de Pathologie 12/2009; 29(6):524-6. · 0.25 Impact Factor
  • Article: Thymic marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue-type in a patient with Sjögren's syndrome and cryoglobulinaemia.
    Pathology 01/2009; 41(7):701-3. · 2.38 Impact Factor
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    Article: Pulmonary veno-occlusive disease: clinical, functional, radiologic, and hemodynamic characteristics and outcome of 24 cases confirmed by histology.
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    ABSTRACT: Pulmonary veno-occlusive disease (PVOD) is defined by specific pathologic changes of the pulmonary veins. A definite diagnosis of PVOD thus requires a lung biopsy or pathologic examination of pulmonary explants or postmortem lung samples. However, lung biopsy is hazardous in patients with severe pulmonary hypertension, and there is a need for noninvasive diagnostic tools in this patient population. Patients with PVOD may be refractory to pulmonary arterial hypertension (PAH)-specific therapy and may even deteriorate with it. It is important to identify such patients as soon as possible, because they should be treated cautiously and considered for lung transplantation if eligible. High-resolution computed tomography of the chest can suggest PVOD in the setting of pulmonary hypertension when it shows nodular ground-glass opacities, septal lines, lymph node enlargement, and pleural effusion. Similarly, occult alveolar hemorrhage found on bronchoalveolar lavage in patients with pulmonary hypertension is associated with PVOD. We conducted the current study to identify additional clinical, functional, and hemodynamic characteristics of PVOD. We retrospectively reviewed 48 cases of severe pulmonary hypertension: 24 patients with histologic evidence of PVOD and 24 randomly selected patients with idiopathic, familial, or anorexigen-associated PAH and no evidence of PVOD after meticulous lung pathologic evaluation. We compared clinical and radiologic findings, pulmonary function, and hemodynamics at presentation, as well as outcomes after the initiation of PAH therapy in both groups. Compared to PAH, PVOD was characterized by a higher male:female ratio and higher tobacco exposure (p < 0.01). Clinical presentation was similar except for a lower body mass index (p < 0.02) in patients with PVOD. At baseline, PVOD patients had significantly lower partial pressure of arterial oxygen (PaO2), diffusing lung capacity of carbon monoxide/alveolar volume (DLCO/VA), and oxygen saturation nadir during the 6-minute walk test (all p < 0.01). Hemodynamic parameters showed a lower mean systemic arterial pressure (p < 0.01) and right atrial pressure (p < 0.05), but no difference in pulmonary capillary wedge pressure. Four bone morphogenetic protein receptor II (BMPR2) mutations have been previously described in PVOD patients; in the current study we describe 2 additional cases of BMPR2 mutation in PVOD. Computed tomography of the chest revealed nodular and ground-glass opacities, septal lines, and lymph node enlargement more frequently in patients with PVOD compared with patients with PAH (all p < 0.05). Among the 16 PVOD patients who received PAH-specific therapy, 7 (43.8%) developed pulmonary edema (mostly with continuous intravenous epoprostenol, but also with oral bosentan and oral calcium channel blockers) at a median of 9 days after treatment initiation. Acute vasodilator testing with nitric oxide and clinical, functional, or hemodynamic characteristics were not predictive of the subsequent occurrence of pulmonary edema on treatment. Clinical outcomes of PVOD patients were worse than those of PAH patients.
    Medicine 07/2008; 87(4):220-33. · 4.35 Impact Factor
  • Article: An unusual clinical presentation of a rare tumor of the thyroid gland: report on one case of leiomyosarcoma and review of literature.
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    ABSTRACT: Primary muscle tumors of the thyroid gland are exceedingly rare. We report on the case of a patient with primary leiomyosarcoma of the thyroid gland and review the literature. An 83-year-old woman complaining of neuropathic pain in her left arm and enlargement of her anterior neck underwent multiple surgical biopsies of the thyroid gland. The tumor was composed of interlacing fascicles of spindle-shaped cells that expressed smooth muscle actin and vimentin but were negative for cytokeratins and thyroglobulin. Ultrastructurally, bundles of myofilaments were present. Magnetic resonance imaging showed a thyroid tumor that directly extended to the adjacent vertebra with an associated pachymeningitis. The patient died 2 months after surgery. The diagnosis of primary leiomyosarcoma of the thyroid gland is difficult and requires numerous clinical, radiologic, and pathologic data. To our knowledge, this case is the first one with such a locoregional extension.
    Annals of Diagnostic Pathology 03/2008; 12(1):50-6. · 0.88 Impact Factor
  • Article: Splenic metastases: clinicopathologic presentation, differential diagnosis, and pathogenesis.
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    ABSTRACT: Splenic metastases from solid tumors, defined as parenchymal lesion, are considered exceptional. Nevertheless, the number of case reports has been increasing due to the improvement of imaging techniques and the long-term follow-up of patients with cancer. Splenic metastases occur in a context of multivisceral disseminated cancer or as a solitary lesion. To provide a general overview of the clinicopathologic features, differential diagnosis, and pathogenesis of splenic metastases. Relevant articles indexed in PubMed (National Library of Medicine) database. The search was based on the following terms: (metastasis or metastases) and spleen. The most common primary sources of splenic metastasis are breast, lung, colorectal, and ovarian carcinomas and melanoma in cases of multivisceral cancer and colorectal and ovarian carcinomas in cases of solitary splenic lesion. Splenectomy can be replaced by less aggressive methods such as fine-needle aspiration or percutaneous biopsy for establishing the diagnosis of solitary splenic metastasis. The main differential diagnoses are primary lymphoma, vascular tumors, and infectious lesions of the spleen. The relative rarity of splenic metastases could be explained by anatomic factors and the inhibitory effect of the splenic microenvironment on the growth of metastatic cells. The analysis of clinical case reports suggests that solitary splenic metastases may result from the growth of an early blood-borne micrometastasis following a period of clinical latency, often several years after the diagnosis of the primary tumor.
    Archives of pathology & laboratory medicine 07/2007; 131(6):965-9. · 2.58 Impact Factor
  • Article: Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases.
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    ABSTRACT: Pulmonary arterial hypertension is a severe complication of connective tissue diseases. It is currently well established that pulmonary arterial hypertension associated with connective tissue diseases such as systemic sclerosis is frequently less responsive or even refractory to pulmonary vasodilator therapies. In that setting, pulmonary venoocclusive disease is believed to contribute to treatment failures. We therefore hypothesized that pulmonary arterial hypertension associated with connective tissue diseases may be associated with obstructive lesions of pulmonary veins. Lung samples from 8 patients with pulmonary arterial hypertension associated with connective tissue disease (4 limited systemic sclerosis, 2 systemic lupus erythematosus, 1 mixed connective tissue diseases, and 1 rheumatoid arthritis) were studied by light microscopy and analyzed by immunohistochemistry (5 postmortem samples, 3 explants after lung transplantation). Findings were compared with 29 pulmonary arterial hypertension cases from patients displaying neither connective tissue diseases nor associated conditions. We found that (a) 6 (75%) of 8 patients with pulmonary arterial hypertension associated with connective tissue diseases showed significant obstructive pulmonary vascular lesions predominating in veins/preseptal venules, as compared with 5 (17.2%) of 29 non-connective tissue diseases control pulmonary arterial hypertension; (b) lesions of small muscular arteries were consistently present in pulmonary arterial hypertension associated with connective tissue diseases, showing mostly intimal fibrosis and thrombotic lesions; and (c) 6 of 8 lung samples from patients with pulmonary arterial hypertension associated with connective tissue diseases revealed perivascular inflammatory infiltration. In conclusion, our study highlights the fact that pulmonary arterial hypertension complicating the course of connective tissue diseases may be characterized by a more frequent involvement of pulmonary veins and may thus explain why these patients are less prone to respond to specific pulmonary arterial hypertension treatment as compared with idiopathic pulmonary arterial hypertension.
    Human Pathlogy 07/2007; 38(6):893-902. · 2.88 Impact Factor
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    Article: Herpes simplex virus lung infection in patients undergoing prolonged mechanical ventilation.
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    ABSTRACT: It is not known whether the isolation of herpes simplex virus (HSV) from lower respiratory tract samples of nonimmunocompromised ventilated patients corresponds to bronchial contamination from the mouth and/or throat, local tracheobronchial excretion of HSV, or true HSV lung involvement (bronchopneumonitis) with its own morbidity/mortality. This prospective, single-center, observational study was conducted to define the frequency, risk factors, and relevance of HSV bronchopneumonitis. All consecutive nonimmunocompromised patients receiving mechanical ventilation for 5 days or more were evaluated. Bronchoalveolar lavage, oropharyngeal swabs, and bronchial biopsies (presence of macroscopic bronchial lesions) were obtained for all who deteriorated clinically with suspected lung infection. HSV bronchopneumonitis was defined as this deterioration, associated with HSV in bronchoalveolar lavage and HSV-specific nuclear inclusions in cells recovered during lavage or bronchial biopsies. HSV bronchopneumonitis was diagnosed in 42 (21%) of the 201 patients who deteriorated clinically, with a mean mechanical ventilation duration before diagnosis of 14 +/- 6 days. Risk factors associated with HSV bronchopneumonitis were oral-labial lesions, HSV in the throat, and macroscopic bronchial lesions seen during bronchoscopy. Patients with HSV bronchopneumonitis were comparable to those without at admission, but their courses were more complicated, with longer duration of mechanical ventilation and intensive care unit stays. HSV bronchopneumonitis is common in nonimmunocompromised patients with prolonged mechanical ventilation, is associated with HSV reactivation or infection of the mouth and/or throat, and seems to be associated with poorer outcome.
    American Journal of Respiratory and Critical Care Medicine 06/2007; 175(9):935-42. · 11.08 Impact Factor
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    Article: Fatal disseminated Acanthamoeba lenticulata infection in a heart transplant patient.
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    ABSTRACT: We report a fatal case of disseminated acanthamebiasis caused by Acanthamoeba lenticulata (genotype T5) in a 39-year-old heart transplant recipient. The diagnosis was based on skin histopathologic results and confirmed by isolation of the ameba from involved skin and molecular analysis of a partial 18S rRNA gene sequence (DF3).
    Emerging infectious diseases 06/2007; 13(5):736-8. · 6.17 Impact Factor
  • Article: Late recurrence of a prostatic adenocarcinoma as a solitary splenic metastasis.
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    ABSTRACT: 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.
    Urologia Internationalis 02/2007; 78(1):86-8. · 0.99 Impact Factor
  • Article: Ocular adnexal marginal zone B cell lymphoma: a clinical and pathologic study of 23 cases.
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    ABSTRACT: 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.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 05/2006; 448(4):506-16. · 2.49 Impact Factor
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    Article: Bronchoalveolar lavage cytological alveolar damage in patients with severe pneumonia.
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    ABSTRACT: 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. 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. 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. 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.
    Critical care (London, England) 03/2006; 10(1):R2. · 4.61 Impact Factor
  • Article: [An unusual cause of jejunal intussusception: heterotopic and hyperplastic Brunner's gland pseudo-tumor].
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    ABSTRACT: 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.
    Gastroentérologie Clinique et Biologique 12/2005; 29(11):1160-3. · 0.80 Impact Factor
  • Article: Skin metastases from unknown origin: role of immunohistochemistry in the evaluation of cutaneous metastases of carcinoma of unknown origin.
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    ABSTRACT: 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.
    Journal of Cutaneous Pathology 10/2005; 32(8):561-6. · 1.56 Impact Factor
  • Article: Sampling variability of liver biopsy in nonalcoholic fatty liver disease.
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    ABSTRACT: 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. 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. 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. 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.
    Gastroenterology 07/2005; 128(7):1898-906. · 11.68 Impact Factor
  • Article: Pericardial ectopic thymoma.
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    ABSTRACT: 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.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 03/2005; 446(2):185-8. · 2.49 Impact Factor
  • Article: Balance between pro and anti-inflammatory cytokines in patients with acute alcoholic hepatitis.
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    ABSTRACT: The ability of endogenous IL-10 to modulate inflammatory response and to limit hepatotoxicity has been shown in several models of liver injury. 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. 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. 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). 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.
    Gastroentérologie Clinique et Biologique 03/2005; 29(3):269-74. · 0.80 Impact Factor
  • Article: Biomarkers for the prediction of liver fibrosis in patients with chronic alcoholic liver disease.
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    ABSTRACT: The aim of this study was to determine the diagnostic use of noninvasive markers of fibrosis in patients with chronic alcoholic liver disease. 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. 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. 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.
    Clinical Gastroenterology and Hepatology 03/2005; 3(2):167-74. · 5.63 Impact Factor
  • Article: The immunology of fibrogenesis in alcoholic liver disease.
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    ABSTRACT: Alcoholic liver disease in humans frequently leads to cirrhosis. Experimental models of hepatic fibrogenesis are available, but extrapolation of those findings to human ethanol-induced liver injury is difficult. Hepatic ethanol-induced fibrosis in humans has often been studied in relatively small patient populations. During the past decade, several animal models and human studies have attributed fibrogenesis in the liver to the role played by hepatocytes, Kupffer cells, endothelial cells, and especially stellate cells. To determine the contribution of the main liver cell types to ethanol-induced fibrogenesis. For that purpose, we studied the expression of the following immunologic parameters: smooth muscle-specific alpha actin (SMSA), CD68, CD34, transforming growth factor beta1, intercellular adhesion molecule 1, and collagen types 1 and 3. The Dako LSAB+ kit (peroxidase method) was used. We recently studied a large cohort of patients with alcoholic liver disease in France. In this cohort, we found 87 cases in which liver biopsies revealed only pericentral injury with nonpathologic portal areas. We compared cases in which the portal areas were nonpathologic with 324 patients in whom staging ranged from F0 to F3. Patients with cirrhosis (F4) were excluded from evaluation. To stage fibrosis, we used the METAVIR system. Furthermore, we selected 40 cases in which the biopsies measured at least 25 mm in length for further histochemical evaluation. Ten additional normal cases from our archives were used as controls. We divided this patient population into the following 5 groups of 10 patients each: group 1A, F0 with steatosis; group 1B, F0 without steatosis; group 2, F0 to F1, central injury; group 3, F3, fibrosis with multiple septa; and group 4, nonpathologic livers (controls). Smooth muscle-specific alpha actin was expressed by stellate cells, pericentrally, with increasing severity and intensity in the advanced stage of fibrosis of group 3, less intense expression was noted in group 2, and expression was practically absent in group 1 and in nonpathologic controls. CD68 was the best marker for Kupffer cells and was expressed diffusely within the lobules in all groups. Its expression correlated directly with the degree of disease severity, progressing from stage I through stage III, but was absent in nonpathologic livers. CD34 was consistently expressed by endothelial cells in the periportal areas in all groups. The expression of collagen type 1 was intense in the bands of fibrosis or bridging, while type 3 expression was poor. Transforming growth factor beta1 and intercellular adhesion molecule 1 were not expressed in any group. In this study, stellate cell activation (SMSA) was most intense pericentrally in the early stages and diffusely with progression to fibrosis and maximum intensity in stage III. Kupffer cell activation, as determined by CD68 expression, was intense and diffuse, while endothelial cells expressed CD34 periportally in a similar manner in all stages. Fibrogenesis in human ethanol injury is due to the activity of stellate cells, Kupffer cells, and to a lesser extent, to endothelial cells.
    Archives of pathology & laboratory medicine 12/2004; 128(11):1230-8. · 2.58 Impact Factor
  • Article: Pulmonary hypertension: CT of the chest in pulmonary venoocclusive disease.
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    ABSTRACT: Pulmonary venoocclusive disease is a rare cause of pulmonary hypertension that is often difficult to distinguish from severe primary pulmonary hypertension. Unfortunately, medical treatment of primary pulmonary hypertension with prostacyclin can be fatal in patients with venoocclusive disease, and an early pretreatment diagnosis of this uncommon condition is critical. The aim of our study was to evaluate this disease noninvasively using CT of the chest. We reviewed cross-referenced records from 1996 to 2001 in our departments of radiology and pathology and identified 15 patients with initial pretreatment CT scans who had pathologically confirmed pulmonary venoocclusive disease. Their CT scans were compared with the CT scans of 15 consecutive patients with pathologically confirmed primary pulmonary hypertension. All patients had undergone a postmortem or posttransplantation examination. Ground-glass opacities were significantly more frequent in pulmonary venoocclusive disease (p = 0.003); the opacities were abundant with random zonal predominance and preferentially centrilobular distribution (p = 0.03). Subpleural septal lines and adenopathy were also significantly more frequent (p < 0.0001). On the initial pretreatment chest CT scan, the presence of ground-glass opacities (particularly with a centrilobular distribution), septal lines, and adenopathy are indicative of pulmonary venoocclusive disease in patients displaying pulmonary hypertension. Caution should be exercised before vasodilator therapy is initiated in the patients whose scans show such radiologic abnormalities.
    American Journal of Roentgenology 07/2004; 183(1):65-70. · 2.78 Impact Factor