Primary pulmonary artery aneurysm in tuberous sclerosis: CT, angiography and pathological study.
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Aneurysm↗
Biomedical subjects
Jacques Cadranel
Publications and source records attributed to Jacques Cadranel.
Lung cancer, a new challenge in the HIV-infected population.
HIV infection predisposes patients to AIDS-defining malignancies, some of which, such as Kaposi's sarcoma and non-Hodgkin lymphoma, can affect the lungs. In 1996, AIDS-related mortality started to fall sharply in industrialized countries following the introduction of highly active antiretroviral treatments (HAART). This was accompanied by an increase in the proportion of deaths attributable to non AIDS-defining solid tumors, and especially lung cancer (LC). The increased risk of LC relative to the general population of the same age seems to be due partly to a higher prevalence of smoking among HIV-infected subjects. The average age of HIV-infected patients at LC diagnosis is about 45 years. Most patients are symptomatic at diagnosis and have only mild or moderate immunosuppression. LC is diagnosed when it is locally advanced or metastatic (stages III-IV) in 75-90% of cases, as in patients with unknown HIV serostatus. Adenocarcinoma is the most frequent histologic type. The prognosis of LC is poorer in HIV-infected patients than in the general population. Data on the efficacy and toxicity of chemotherapy in this setting are rare and rather imprecise. Surgery remains the reference treatment for localized disease in patients with adequate functional status and general health, regardless of their immune status. Prospective clinical trials are needed to define the optimal LC treatment strategies in HIV-infected patients.
Global Health↗
Prognostic factors and outcome of human herpesvirus 8-associated primary effusion lymphoma in patients with AIDS.
PURPOSE: Primary effusion lymphoma (PEL) is a rare high-grade B-cell non-Hodgkin's lymphoma associated with Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) infection, and is mostly observed in the course of HIV infection. The prognosis is poor, with reported median survival time shorter than 6 months. To date, no prognostic factor has been identified in this subset of lymphoma. PATIENTS AND METHODS: We describe here a large series of HIV-infected patients with PEL, including 28 cases diagnosed in six centers during an 11-year time period. Prognosis analysis was performed using a Cox proportional hazard regression model. Statistically significant covariates were further analyzed in a forward, stepwise multivariate model. RESULTS: After a median follow-up of 3.8 years (range, 10 months to 10.8 years), nine patients (32%) were still alive, and eight of them remained progression free. The median survival was 6.2 months, and the 1-year overall survival rate was 39.3%. Fourteen patients (50%) achieved complete remission, with a 1-year disease-free survival rate at 78.6%. In a multivariate analysis, only a performance status more than 2 (hazard ratio, 5.84; 95% CI, 1.76 to 19.33) and the absence of highly active antiretroviral therapy (HAART) before PEL diagnosis (hazard ratio, 3.26; 95% CI, 1.14 to 9.34) were found to be independent predictors for shorter survival. CONCLUSION: Based on a retrospective series of 28 patients, two prognostic factors were identified as being independently associated with impaired clinical outcome in HIV-related PEL--(1) a poor performance status and (2) the absence of HAART before PEL diagnosis.
Acquired Immunodeficiency Syndrome↗
[Drug-associated interstitial lung disease: a diagnostic challenge].
Drugs are frequently incriminated as the cause of interstitial pneumonia. There are two major mechanisms of drug-associated interstitial lung disease: direct toxicity and immunoallergic reaction. When a drug is suspected, the difficulty lies in obtaining proof. The chronology of the disease and its manifestations together with earlier evidence reported in the literature can lead to a tentative diagnosis of drug-associated interstitial pneumonia. Proof is obtained through surveillance during the disease course. In nearly all patients, therapeutic decisions must be taken on the basis of suspected drug involvement.
Bronchoalveolar Lavage↗
Quantitative fish determination of chromosome 3 arm imbalances in lung tumors by automated image cytometry.
BACKGROUND: Clonal heterogeneity is a major difficulty in the analysis of chromosome rearrangements within tumor tissue. Using in situ hybridization, a cell-to-cell analysis can be performed and should allow a better understanding of the genetic process. In addition, detection of pre-neoplastic lesions with only a few cells involved may improve the diagnosis of such lesions and their precocious treatment. MATERIAL/METHODS: Automated analysis was performed on tissue sections with our previously described two-color fluorescence in situ hybridization-based method for quantitative determination of chromosome arm imbalance. The imbalance between the long and short arms of chromosome 3 was determined in 24 cases of non-small-cell and small-cell lung cancers in which only small snap-frozen sections were used, allowing other simultaneous molecular analyses, such as TP53 gene mutation detection. RESULTS: Specifically developed software allowed localization of each nucleus within the section with regard to its chromosome imbalance and to reconstitute a multi-clonal panel within an apparently homogeneous sample. In some cases, discrepancies in the imbalance values were observed between the biopsy and the tumor obtained after surgery from the same patient. CONCLUSIONS: The discrepancies observed between biopsies and tumors, likely linked to the samples' heterogeneity, demonstrate the necessity to analyze tissue sections collected at various locations. The fully automated approach developed in this study rendered such investigations possible.
Cell Transformation, Neoplastic↗
Rapid and sensitive p53 alteration analysis in biopsies from lung cancer patients using a functional assay and a universal oligonucleotide array: a prospective study.
PURPOSE: Molecular profiling of alterations associated with lung cancer holds the promise to define clinical parameters such as response to treatment or survival. Because <5% of small cell lung cancers and <30% of non-small cell lung cancers are surgically resectable, molecular analysis will perforce rely on routinely available clinical samples such as biopsies. Identifying tumor mutations in such samples will require a sensitive and robust technology to overcome signal from excess amounts of normal DNA. EXPERIMENTAL DESIGN: p53 mutation status was assessed from the DNA and RNA of biopsies collected prospectively from 83 patients with lung cancer. Biopsies were obtained either by conventional bronchoscopy or computed tomography-guided percutaneous biopsy. Matched surgical specimens were available for 22 patients. Three assays were used: direct sequencing; a functional assay in yeast; and a newly developed PCR/ligase detection reaction/Universal DNA array assay. RESULTS: Using the functional assay, p53 mutation was found in 62% of biopsies and 64% of surgical specimens with a concordance of 80%. The sensitivity of the functional assay was determined to be 5%. Direct sequencing confirmed mutations in 92% of surgical specimens but in only 78% of biopsies. The DNA array confirmed 100% of mutations in both biopsies and surgical specimens. Using this newly developed DNA array, we demonstrate the feasibility of directly identifying p53 mutations in clinical samples containing <5% of tumor cells. CONCLUSIONS: The versatility and sensitivity of this new array assay should allow additional development of mutation profiling arrays that could be applied to biological samples with a low tumor cell content such as bronchial aspirates, bronchoalveolar lavage fluid, or serum.
Aged↗
Sarcoidosis in HIV-infected patients in the era of highly active antiretroviral therapy.
To analyze the impact of highly active antiretroviral therapy (HAART) on the characteristics and outcome of sarcoidosis in patients infected with human immunodeficiency virus (HIV), we identified HIV-infected patients in whom sarcoidosis was diagnosed between 1996 and 2000 from the admission registers of the pneumology departments of 12 hospitals in the Paris region (France). Sarcoidosis was diagnosed in 11 HIV-infected patients, of whom 8 were receiving HAART. HIV infection was diagnosed before sarcoidosis in 9 cases. At diagnosis of sarcoidosis, the mean CD4 cell count (+/-SD) was 390+/-213 cells/mm(3), and the mean plasma virus load was 4002+/-10,183 copies/mL. Sarcoidosis occurred several months after HAART introduction, when the CD4 cell count had increased and the plasma HIV load had decreased. Clinical and radiological characteristics, laboratory values for bronchoalveolar lavage fluid samples, and outcome after a long follow-up were similar for the patients receiving HAART and for HIV-uninfected patients.
Anti-HIV Agents↗
Clonality analysis of alveolar B lymphocytes contributes to the diagnostic strategy in clinical suspicion of pulmonary lymphoma.
The diagnostic procedure of chronic pulmonary opacities may envisage the search for non-Hodgkin lymphoma (NHL). Previous retrospective studies have shown that clonality analysis of bronchoalveolar B lymphocytes could reflect the clonality of pulmonary lymphocytes. Our objective was to define the diagnostic usefulness of bronchoalveolar lavage (BAL) B-lymphocyte clonality analysis in the setting of a clinical suspicion of both primary and secondary pulmonary lymphoma. A prospective BAL fluid B-cell clonality analysis was performed by polymerase chain reaction (PCR) in 106 consecutive patients presenting with a clinical suspicion of pulmonary NHL. Diagnosis was pulmonary B-cell lymphoma for 22 patients (13 primary and 9 secondary). When compared, pulmonary biopsy and BAL fluid have clonal identity. The detection of a strong B-cell clonal population in BAL fluid was associated with the diagnosis of pulmonary NHL (P <.0001), with a 97% specificity and a 95% negative predictive value. Thus, the absence of a dominant B-cell clone detection in BAL fluid could help to dismiss invasive investigations of pulmonary lesions. The detection of a dominant B-cell clone would lead to the performance of a pulmonary biopsy to get histologic diagnosis in primary pulmonary lymphoma and, by contrast, would avoid the need for biopsy in the setting of a secondary pulmonary lymphoma.
B-Lymphocytes↗
Changes in the pattern of respiratory diseases necessitating hospitalization of HIV-infected patients since the advent of highly active antiretroviral therapy.
The incidence rates of opportunistic diseases, hospital admission and death have fallen markedly since the advent of highly active antiretroviral therapy (HAART). We examined the impact of HAART on the pattern of HIV-related respiratory diseases necessitating hospitalization. We retrospectively compared the numbers and etiologies of respiratory diseases diagnosed in HIV-infected patients hospitalized in the chest department of a Paris university hospital during the three years preceding widespread prescription of HAART in France (era 1, starting in July 1993) and the first three years of widespread HAART prescription (era 2, starting in July 1996). Respectively, 207 and 119 HIV-infected patients were admitted for respiratory disease in era 1 and era 2. Only 31.1% of patients admitted during era 2 were receiving HAART. Pulmonary opportunistic infections other than Pneumocystis carinii pneumonia (PCP) (p = 0.0008) and exacerbations of chronic bronchial disease due to gram-negative bacilli (p = 0.04) virtually disappeared in era 2. In contrast, PCP, bacterial pneumonia, tuberculosis, pulmonary Kaposi's sarcoma and pulmonary non-Hodgkin lymphoma showed only a twofold decrease in era 2, while lung cancer was more frequent (p = 0.004). The frequency of severe respiratory diseases necessitating hospitalization of HIV-infected patients has fallen since the advent of HAART, and their etiologic distribution has changed.
AIDS-Related Opportunistic Infections↗
[Pulmonary calcified micronodules].
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Adult↗
[Treatment considerations for hepatopulmonary syndrome].
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Adult↗
[Intra-thoracic opacities and masses].
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Humans↗
Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients.
PURPOSE: To determine incidence of non-AIDS-defining cancers (NADC) in HIV-infected patients before (P1) and during (P2) the use of highly active antiretroviral therapy (HAART) relative to that observed in the French general population (FGP) of the same age and sex. PATIENTS AND METHODS: Sex- and age-adjusted NADC standardized incidence ratios (SIR), with FGP as reference, were estimated in 1992 to 1995 (P1) and in 1996 to 1999 (P2) in a French Hospital Database on HIV prospective hospital cohort study. RESULTS: NADCs were diagnosed in 260 patients during P1 and 391 patients during P2 among the 77,025 patients included in the database between January 1, 1992, and December 31, 1999. Estimated incidence of all cancers was higher in HIV-infected men than in FGP during both periods (P1 SIR = 2.36 and P2 SIR = 1.91). No excess of cancers was observed among HIV-infected women in either period. Incidence of all cancers did not change from P1 to P2 in either sex (SIR = 0.96 for men and 1.00 for women). In contrast, incidence of Hodgkin's disease (HD) was higher than in FGP in both sexes and both periods and increased in P2 as compared with P1; incidence of lung cancer was higher in both sexes during P2. CONCLUSION: Relative to FGP, the overall incidence of NADCs was increased in HIV-infected men but not in women and did not differ between P1 and P2. Only HD was much more common in HIV infection, and the potential role of HAART on HD cannot be excluded.
Adolescent↗
Life-threatening hemoptysis in adults with community-acquired pneumonia due to Panton-Valentine leukocidin-secreting Staphylococcus aureus.
Three new consecutive cases of life-threatening hemoptysis in adults with community-acquired pneumonia due to Panton-Valentine leukocidin-secreting Staphylococcus aureus are presented, focusing on the particular clinical presentation of this new entity. Between December 1999 and March 2001, three adults aged from 23 to 67 years were admitted to our respiratory intensive care unit for massive hemoptysis and septic shock associated with community-acquired Staphylococcus aureus pneumonia. Isolates were sent to the Centre National de Référence des Toxémies Staphylococciques in Lyon, France, where they were found to secrete Panton-Valentive leukocidin. The clinical course was similar in the three patients, with massive hemoptysis and septic shock necessitating mechanical ventilation. Two patients died rapidly; necropsy showed pulmonary vascular necrosis in one of them. The third patient recovered after appropriate antibiotic therapy. Leukocidin/neutrophil interactions in the pulmonary vasculature may cause severe hemoptysis in patients with community-acquired Staphylococcus aureus pneumonia secreting Panton-Valentine leukocidin. Adult patients with massive hemoptysis and suspected community-acquired pneumonia should receive antibiotic regimens covering Staphylococcus aureus.
Adult↗
Liver transplantation for hepatopulmonary syndrome: a ten-year experience in Paris, France.
BACKGROUND: Although the possibility of reversing hepatopulmonary syndrome (HPS) after liver transplantation is now well established, the proportion of patients in whom reversibility is observed and the time to resolution of HPS remain uncertain. METHODS: We analyzed the outcome of all adult patients with HPS who underwent orthotopic liver transplantation in all the liver transplant centers in Paris, during a 10-year period. RESULTS: Twenty-three adult patients (median age, 47 years; range, 14-64) underwent transplantation in four institutions. Median PaO(2) was 52 (range, 32-67) mm Hg and median alveolar-arterial oxygen gradient was 66 mm Hg. When patients were breathing 100% O(2), median PaO(2) was 310 (range, 74-663) mm Hg. Median isotopic shunt ratio was 33% (range, 0-80%). The overall mortality during the study period was 30.5% (7/23). Perioperative mortality was 8.5%, whereas late mortality was 22%. None of the preoperative characteristics of HPS (isotopic shunt ratio, PaO(2) on room air or on 100% oxygen) was associated with overall postoperative mortality. Of the 21 patients surviving the perioperative period (median follow-up, 17 months; range, 0.5-72), a decrease in alveolar-arterial oxygen gradient of at least 5 mm Hg and at least 10 mm Hg was observed in 21 of 21 and in 18 of 21 patients, respectively, with great variations in the time of improvement. The threshold of 70 mm Hg was reached in 15 patients. The lower the preoperative PaO(2), the longer the time to reach this point. CONCLUSION: Our data strongly support the role of orthotopic liver transplantation in adult patients with HPS, regardless of its severity.
Adolescent↗
Improvement of symptomatic human immunodeficiency virus-related lymphoid interstitial pneumonia in patients receiving highly active antiretroviral therapy.
To analyze the impact of highly active antiretroviral therapy on lymphoid interstitial pneumonia (LIP), we reviewed the medical files of 5 human immunodeficiency virus (HIV)-infected patients in whom LIP was diagnosed during 1996-2001 who had never previously received antiretroviral treatment. Patients were mildly immunosuppressed at the time of diagnosis of LIP but had high plasma HIV loads and marked circulating and pulmonary CD8 hyperlymphocytosis. All patients improved clinically, radiologically, and functionally; improvement was accompanied by a drastic reduction in the virus load and an increase in the CD4 lymphocyte count.
AIDS-Related Opportunistic Infections↗
[Bronchoalveolar carcinoma].
Bronchoalveolar carcinoma is one of the four histologic subtypes of adenocarcinoma and its incidence is increasing. It grows in a lepidic fashion along the alveolar septa without invasive growth. The lack of invasive growth is an essential criterion based on data indicating that patients may be curable by surgical resection. The revised definition seems to be suitable for its solitary nodular form but less for multifocal or pneumonic-type form. High-resolution lung CT-scan is necessary to evaluate pulmonary involvement because of the high frequency of multifocal disease at initial presentation and because of the presence of ground glass opacity that could be one of the first manifestation of cancer bronchiolo-alvéolaireon CT. Therapeutic management does not differ from the one of non small cell lung cancer. Solitary nodules are treated by surgical resection with a good prognosis while multifocal and/or pneumonic forms are treated by systemic chemotherapy with a worse prognosis.
Adenocarcinoma, Bronchiolo-Alveolar↗
Hepatocyte growth factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: role in tumor progression and death.
Increased numbers of tumor-infiltrating neutrophils are linked to poorer outcome in patients with adenocarcinoma of the bronchioloalveolar carcinoma (BAC) subtype. Hepatocyte growth factor (HGF) is a pleiotropic cytokine operating through activation of the proto-oncogene c-met and is a factor of poor prognosis in various cancers. Reports that neutrophils produce HGF led us to investigate their participation in the aerogenous spread of tumor cells and the prognosis of BAC, through the effect of HGF on c-met-expressing tumor cells. Immunoreactive HGF was detected in bronchoalveolar lavage fluid (BALF) supernatants from 34 of 36 patients, whereas it was undetectable in BALF from healthy controls. The HGF thus detected was locally produced, because HGF mRNA was expressed by the patients' fresh alveolar cells, and HGF protein was detected in 24-h culture supernatants. In immunocytochemical studies of BALF cytospin preparations and tumor specimens from the patients, neutrophils were always HGF-positive, whereas alveolar macrophages and tumor cells gave inconsistent results. Alveolar neutrophil-derived HGFs induced significant, concentration-dependent migration of BAC-derived tumor cells in vitro, and this effect was inhibited by anti-HGF neutralizing antibodies. Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha (present in the lung tumor microenvironment) provoked HGF release from neutrophil intracellular stocks, and the capacity of blood neutrophils from BAC patients to produce HGF was unaltered. Immunochemical studies of c-met expression in BALF cytospin preparations and tumor sections showed that most HGF receptor-bearing cells were tumor cells. High HGF levels in BALF supernatants were significantly associated with poorer outcome in patients with BAC and were an independent predictor of clinical outcome in multivariate analysis. Altogether, our results support the notion that BAC generates a local environment that attracts functionally normal neutrophils from peripheral blood and leads to neutrophil release of biologically active HGF on contact with HGF receptor-expressing tumor cells, thereby contributing to poorer patient outcome.
Adenocarcinoma, Bronchiolo-Alveolar↗